automated-analytics/bionlp2004

1{"id": "0", "text": "Since HUVECs released superoxide anions in response to TNF , and H2O2 induces VCAM-1 , PDTC may act as a radical scavenger .", "annotated_text": "Since <cell_line>HUVECs</cell_line> released superoxide anions in response to TNF , and H2O2 induces <protein>VCAM-1</protein> , PDTC may act as a radical scavenger ."}2{"id": "1", "text": "Although ICAM-1 induction was unaffected , inhibitors of NADPH oxidase ( apocynin ) or cytochrome P-450 ( SKF525a ) suppressed VCAM-1 induction by TNF , revealing that several radical-generating systems are involved in its regulation .", "annotated_text": "Although <protein>ICAM-1</protein> induction was unaffected , inhibitors of <protein>NADPH oxidase</protein> ( apocynin ) or <protein>cytochrome P-450</protein> ( SKF525a ) suppressed <protein>VCAM-1</protein> induction by TNF , revealing that several radical-generating systems are involved in its regulation ."}3{"id": "2", "text": "PDTC , apocynin , or SKF525a decreased adhesion of monocytic U937 cells to TNF-treated HUVECs ( by 75 % at 100 mumol/L PDTC ) .", "annotated_text": "PDTC , apocynin , or SKF525a decreased adhesion of <cell_line>monocytic U937 cells</cell_line> to <cell_line>TNF-treated HUVECs</cell_line> ( by 75 % at 100 mumol/L PDTC ) ."}4{"id": "3", "text": "Inhibition by anti-VCAM-1 monoclonal antibody 1G11 indicated that U937 adhesion was VCAM-1 dependent and suppression by antioxidants was due to reduced VCAM-1 induction .", "annotated_text": "Inhibition by <protein>anti-VCAM-1 monoclonal antibody</protein> <protein>1G11</protein> indicated that <cell_line>U937</cell_line> adhesion was <protein>VCAM-1</protein> dependent and suppression by antioxidants was due to reduced <protein>VCAM-1</protein> induction ."}5{"id": "4", "text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"}6{"id": "5", "text": "Displacement of an E-box-binding repressor by basic helix-loop-helix proteins : implications for B-cell specificity of the immunoglobulin heavy-chain enhancer .", "annotated_text": "Displacement of an <protein>E-box-binding repressor</protein> by <protein>basic helix-loop-helix proteins</protein> : implications for B-cell specificity of the <dna>immunoglobulin heavy-chain enhancer</dna> ."}7{"id": "6", "text": "The activity of the immunoglobulin heavy-chain ( IgH ) enhancer is restricted to B cells , although it binds both B-cell-restricted and ubiquitous transcription factors .", "annotated_text": "The activity of the <dna>immunoglobulin heavy-chain ( IgH ) enhancer</dna> is restricted to <cell_type>B cells</cell_type> , although it binds both <protein>B-cell-restricted and ubiquitous transcription factors</protein> ."}8{"id": "7", "text": "Activation of the enhancer in non-B cells upon overexpression of the basic helix-loop-helix ( bHLH ) protein E2A appears to be mediated not only by the binding of E2A to its cognate E box but also by the resulting displacement of a repressor from that same site .", "annotated_text": "Activation of the <dna>enhancer</dna> in <cell_type>non-B cells</cell_type> upon overexpression of the <protein>basic helix-loop-helix ( bHLH ) protein</protein> <protein>E2A</protein> appears to be mediated not only by the binding of <protein>E2A</protein> to its cognate <dna>E box</dna> but also by the resulting displacement of a <protein>repressor</protein> from that same site ."}9{"id": "8", "text": "We have identified a `` two-handed '' zinc finger protein , denoted ZEB , the DNA-binding specificity of which mimics that of the cellular repressor .", "annotated_text": "We have identified a <protein>`` two-handed '' zinc finger protein</protein> , denoted <protein>ZEB</protein> , the DNA-binding specificity of which mimics that of the <protein>cellular repressor</protein> ."}10{"id": "9", "text": "By employing a derivative E box that binds ZEB but not E2A , we have shown that the repressor is active in B cells and the IgH enhancer is silenced in the absence of binding competition by bHLH proteins .", "annotated_text": "By employing a derivative <dna>E box</dna> that binds <protein>ZEB</protein> but not <protein>E2A</protein> , we have shown that the <protein>repressor</protein> is active in <cell_type>B cells</cell_type> and the <dna>IgH enhancer</dna> is silenced in the absence of binding competition by <protein>bHLH proteins</protein> ."}11{"id": "10", "text": "Hence , we propose that a necessary prerequisite of enhancer activity is the B-cell-specific displacement of a ZEB-like repressor by bHLH proteins .", "annotated_text": "Hence , we propose that a necessary prerequisite of <dna>enhancer</dna> activity is the B-cell-specific displacement of a <protein>ZEB-like repressor</protein> by <protein>bHLH proteins</protein> ."}12{"id": "11", "text": "Inhibition of NF-kappa B by sodium salicylate and aspirin [ see comments ]", "annotated_text": "Inhibition of <protein>NF-kappa B</protein> by sodium salicylate and aspirin [ see comments ]"}13{"id": "12", "text": "The transcription factor nuclear factor-kappa B ( NF-kappa B ) is critical for the inducible expression of multiple cellular and viral genes involved in inflammation and infection including interleukin-1 ( IL-1 ) , IL-6 , and adhesion molecules .", "annotated_text": "The <protein>transcription factor</protein> <protein>nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) is critical for the inducible expression of multiple <dna>cellular and viral genes</dna> involved in inflammation and infection including <protein>interleukin-1</protein> ( <protein>IL-1</protein> ) , <protein>IL-6</protein> , and <protein>adhesion molecules</protein> ."}14{"id": "13", "text": "The anti-inflammatory drugs sodium salicylate and aspirin inhibited the activation of NF-kappa B , which further explains the mechanism of action of these drugs .", "annotated_text": "The anti-inflammatory drugs sodium salicylate and aspirin inhibited the activation of <protein>NF-kappa B</protein> , which further explains the mechanism of action of these drugs ."}15{"id": "14", "text": "This inhibition prevented the degradation of the NF-kappa B inhibitor , I kappa B , and therefore NF-kappa B was retained in the cytosol .", "annotated_text": "This inhibition prevented the degradation of the <protein>NF-kappa B inhibitor</protein> , <protein>I kappa B</protein> , and therefore <protein>NF-kappa B</protein> was retained in the cytosol ."}16{"id": "15", "text": "Sodium salicylate and aspirin also inhibited NF-kappa B -dependent transcription from the Ig kappa enhancer and the human immunodeficiency virus ( HIV ) long terminal repeat ( LTR ) in transfected T cells .", "annotated_text": "Sodium salicylate and aspirin also inhibited <protein>NF-kappa B</protein> -dependent transcription from the <dna>Ig kappa enhancer</dna> and the <dna>human immunodeficiency virus ( HIV ) long terminal repeat</dna> ( <dna>LTR</dna> ) in <cell_line>transfected T cells</cell_line> ."}17{"id": "16", "text": "Effects of the antisense myb expression on hemin- and erythropoietin- induced erythroid differentiation of K562 cells .", "annotated_text": "Effects of the antisense myb expression on hemin- and erythropoietin- induced erythroid differentiation of <cell_line>K562 cells</cell_line> ."}18{"id": "17", "text": "In order to elucidate the role of c-myb gene in erythroid differentiation of K562 cell induced by hemin ( Hm ) and erythropoietin ( Epo ) , we constructed recombinant plasmid that could produce antisense myb RNA after induction with dexamethasone .", "annotated_text": "In order to elucidate the role of <dna>c-myb gene</dna> in erythroid differentiation of <cell_line>K562 cell</cell_line> induced by <protein>hemin</protein> ( <protein>Hm</protein> ) and <protein>erythropoietin</protein> ( <protein>Epo</protein> ) , we constructed <dna>recombinant plasmid</dna> that could produce <rna>antisense myb RNA</rna> after induction with dexamethasone ."}19{"id": "18", "text": "During treatment with Hm , K562 cells constitutively expressed c-myb mRNA , and 50 % of them began to synthesize hemoglobin ( Hb ) .", "annotated_text": "During treatment with <protein>Hm</protein> , <cell_line>K562 cells</cell_line> constitutively expressed <rna>c-myb mRNA</rna> , and 50 % of them began to synthesize <protein>hemoglobin</protein> ( <protein>Hb</protein> ) ."}20{"id": "19", "text": "Expression of antisense myb RNA reduced the amount of c-myb mRNA , and the percentage of Hb-synthesizing cells was decreased to 20 % .", "annotated_text": "Expression of <rna>antisense myb RNA</rna> reduced the amount of <rna>c-myb mRNA</rna> , and the percentage of <cell_line>Hb-synthesizing cells</cell_line> was decreased to 20 % ."}21{"id": "20", "text": "In the presence of Epo , c-myb mRNA declined and 20 % of K562 cells synthesized Hb regardless of antisense myb RNA expression .", "annotated_text": "In the presence of <protein>Epo</protein> , <rna>c-myb mRNA</rna> declined and 20 % of <cell_line>K562 cells</cell_line> synthesized <protein>Hb</protein> regardless of <rna>antisense myb RNA</rna> expression ."}22{"id": "21", "text": "It is suggested that constitutive expression of c-myb mRNA is necessary for Hm -induced differentiation , and that a decrease in the amount of c-myb mRNA induced by antisense myb RNA expression suppresses Hm -induced differentiation .", "annotated_text": "It is suggested that constitutive expression of <rna>c-myb mRNA</rna> is necessary for <protein>Hm</protein> -induced differentiation , and that a decrease in the amount of <rna>c-myb mRNA</rna> induced by <rna>antisense myb RNA</rna> expression suppresses <protein>Hm</protein> -induced differentiation ."}23{"id": "22", "text": "The amount of c-myb mRNA in K562 cells was reduced during the differentiation induced by Epo .", "annotated_text": "The amount of <rna>c-myb mRNA</rna> in <cell_line>K562 cells</cell_line> was reduced during the differentiation induced by <protein>Epo</protein> ."}24{"id": "23", "text": "Expression of GATA-1 mRNA was almost constant during Hm -induced differentiation , but increased during Epo treatment .", "annotated_text": "Expression of <rna>GATA-1 mRNA</rna> was almost constant during <protein>Hm</protein> -induced differentiation , but increased during <protein>Epo</protein> treatment ."}25{"id": "24", "text": "It is supposed that the mechanism of Hm -induced differentiation is distinguished from that of Epo -induced differentiation in K562 cells .", "annotated_text": "It is supposed that the mechanism of <protein>Hm</protein> -induced differentiation is distinguished from that of <protein>Epo</protein> -induced differentiation in <cell_line>K562 cells</cell_line> ."}26{"id": "25", "text": "Prenatal immune challenge alters the hypothalamic-pituitary-adrenocortical axis in adult rats .", "annotated_text": "Prenatal immune challenge alters the hypothalamic-pituitary-adrenocortical axis in adult rats ."}27{"id": "26", "text": "We investigated whether non-abortive maternal infections would compromise fetal brain development and alter hypothalamic-pituitary-adrenocortical ( HPA ) axis functioning when adult .", "annotated_text": "We investigated whether non-abortive maternal infections would compromise fetal brain development and alter hypothalamic-pituitary-adrenocortical ( HPA ) axis functioning when adult ."}28{"id": "27", "text": "To study putative teratogenic effects of a T cell-mediated immune response versus an endotoxic challenge , 10-d-pregnant rats received a single intraperitoneal injection of 5 x 10 ( 8 ) human red blood cells ( HRBC ) or gram-negative bacterial endotoxin ( Escherichia coli LPS : 30 micrograms/kg ) .", "annotated_text": "To study putative teratogenic effects of a T cell-mediated immune response versus an endotoxic challenge , 10-d-pregnant rats received a single intraperitoneal injection of 5 x 10 ( 8 ) <cell_type>human red blood cells</cell_type> ( <cell_type>HRBC</cell_type> ) or gram-negative bacterial endotoxin ( Escherichia coli LPS : 30 micrograms/kg ) ."}29{"id": "28", "text": "The adult male progeny ( 3 mo old ) of both experimental groups showed increased basal plasma corticosterone levels .", "annotated_text": "The adult male progeny ( 3 mo old ) of both experimental groups showed increased basal plasma corticosterone levels ."}30{"id": "29", "text": "In addition , after novelty stress the HRBC group , but not the LPS group , showed increased ACTH and corticosterone levels .", "annotated_text": "In addition , after novelty stress the <cell_type>HRBC</cell_type> group , but not the <cell_line>LPS group</cell_line> , showed increased ACTH and corticosterone levels ."}31{"id": "30", "text": "Both groups showed substantial decreases in mineralocorticoid ( MR ) and glucocorticoid receptor ( GR ) levels in the hippocampus , a limbic brain structure critical for HPA axis regulation , whereas GR concentrations in the hypothalamus were unchanged and in anterior pituitary were slightly increased .", "annotated_text": "Both groups showed substantial decreases in mineralocorticoid ( MR ) and glucocorticoid receptor ( GR ) levels in the hippocampus , a limbic brain structure critical for HPA axis regulation , whereas <protein>GR</protein> concentrations in the hypothalamus were unchanged and in anterior pituitary were slightly increased ."}32{"id": "31", "text": "HRBC and LPS indeed stimulated the maternal immune system as revealed by specific anti-HRBC antibody production and enhanced IL-1 beta mRNA expression in splenocytes , respectively .", "annotated_text": "<cell_type>HRBC</cell_type> and LPS indeed stimulated the maternal immune system as revealed by specific <protein>anti-HRBC antibody</protein> production and enhanced IL-1 beta mRNA expression in <cell_type>splenocytes</cell_type> , respectively ."}33{"id": "32", "text": "This study demonstrates that a T cell-mediated immune response as well as an endotoxic challenge during pregnancy can induce anomalies in HPA axis function in adulthood .", "annotated_text": "This study demonstrates that a T cell-mediated immune response as well as an endotoxic challenge during pregnancy can induce anomalies in HPA axis function in adulthood ."}34{"id": "33", "text": "Clinically , it may be postulated that disturbed fetal brain development due to prenatal immune challenge increases the vulnerability to develop mental illness involving inadequate responses to stress .", "annotated_text": "Clinically , it may be postulated that disturbed fetal brain development due to prenatal immune challenge increases the vulnerability to develop mental illness involving inadequate responses to stress ."}35{"id": "34", "text": "A low NM23.H1 gene expression identifying high malignancy human melanomas .", "annotated_text": "A low <dna>NM23.H1 gene</dna> expression identifying high malignancy human melanomas ."}36{"id": "35", "text": "The NM23 gene has been proposed as a metastasis-suppressor gene , and its use has been suggested as prognostic factor .", "annotated_text": "The <dna>NM23 gene</dna> has been proposed as a <dna>metastasis-suppressor gene</dna> , and its use has been suggested as prognostic factor ."}37{"id": "36", "text": "NM23 was identified in a system of murine melanoma cell lines , in which an inverse relationship was found between NM23 expression and metastatic ability .", "annotated_text": "<protein>NM23</protein> was identified in a system of <cell_line>murine melanoma cell lines</cell_line> , in which an inverse relationship was found between <protein>NM23</protein> expression and metastatic ability ."}38{"id": "37", "text": "In a human malignant melanoma study NM23 expression was found to be significantly lower in metastases that developed less than 24 months after diagnosis of the primary tumours .", "annotated_text": "In a human malignant melanoma study <protein>NM23</protein> expression was found to be significantly lower in metastases that developed less than 24 months after diagnosis of the primary tumours ."}39{"id": "38", "text": "The present paper studies the expression of the NM23.H1 gene in cell lines which derive from primary or metastatic human malignant melanomas in relation to staging , infiltration degree , lymphocytic infiltration , cell morphology , cell pigmentation , karyotype , and disease-free survival .", "annotated_text": "The present paper studies the expression of the <dna>NM23.H1 gene</dna> in <cell_line>cell lines</cell_line> which derive from primary or metastatic human malignant melanomas in relation to staging , infiltration degree , lymphocytic infiltration , cell morphology , cell pigmentation , karyotype , and disease-free survival ."}40{"id": "39", "text": "The level of mRNA expression of the NM23 gene is significantly lower in cell lines that derive from more infiltrating primary melanomas than in cell lines obtained from less infiltrating tumours .", "annotated_text": "The level of mRNA expression of the <dna>NM23 gene</dna> is significantly lower in <cell_line>cell lines</cell_line> that derive from more infiltrating primary melanomas than in <cell_line>cell lines</cell_line> obtained from less infiltrating tumours ."}41{"id": "40", "text": "Moreover , cell lines derived from tumours of patients with a disease-free survival of more than 24 months ( 24-58 months ) express the NM23 gene at higher levels than cell lines obtained from melanomas of patients with a disease-free survival of less than 24 months ( 6-15 months ) .", "annotated_text": "Moreover , <cell_line>cell lines</cell_line> derived from tumours of patients with a disease-free survival of more than 24 months ( 24-58 months ) express the <dna>NM23 gene</dna> at higher levels than <cell_line>cell lines</cell_line> obtained from melanomas of patients with a disease-free survival of less than 24 months ( 6-15 months ) ."}42{"id": "41", "text": "Activation of a novel serine/threonine kinase that phosphorylates c-Fos upon stimulation of T and B lymphocytes via antigen and cytokine receptors .", "annotated_text": "Activation of a novel <protein>serine/threonine kinase</protein> that phosphorylates <protein>c-Fos</protein> upon stimulation of <cell_type>T and B lymphocytes</cell_type> via antigen and <protein>cytokine receptors</protein> ."}43{"id": "42", "text": "Ligation of Ag receptors in T and B lymphocytes initiates signal transduction cascades which alter the expression of genes that regulate cellular proliferation and differentiation .", "annotated_text": "Ligation of <protein>Ag receptors</protein> in <cell_type>T and B lymphocytes</cell_type> initiates signal transduction cascades which alter the expression of genes that regulate cellular proliferation and differentiation ."}44{"id": "43", "text": "The transmission of signals from the membrane to the nucleus is mediated principally through the action of protein tyrosine and serine/threonine kinases .", "annotated_text": "The transmission of signals from the membrane to the nucleus is mediated principally through the action of <protein>protein tyrosine and serine/threonine kinases</protein> ."}45{"id": "44", "text": "We have identified and characterized a novel serine/threonine kinase that phosphorylated the proto-oncogene product , c-Fos , and is termed Fos kinase .", "annotated_text": "We have identified and characterized a novel <protein>serine/threonine kinase</protein> that phosphorylated the <protein>proto-oncogene product</protein> , <protein>c-Fos</protein> , and is termed <protein>Fos kinase</protein> ."}46{"id": "45", "text": "Fos kinase was rapidly activated after ligation of the CD3 and CD2 receptors in Jurkat and normal human T lymphocytes and in response to IL-6 and anti-IgM in the human B cell lines AF10 and Ramos , respectively .", "annotated_text": "<protein>Fos kinase</protein> was rapidly activated after ligation of the <protein>CD3 and CD2 receptors</protein> in <cell_line>Jurkat</cell_line> and <cell_type>normal human T lymphocytes</cell_type> and in response to <protein>IL-6</protein> and <protein>anti-IgM</protein> in the <cell_line>human B cell lines</cell_line> <cell_line>AF10</cell_line> and <cell_line>Ramos</cell_line> , respectively ."}47{"id": "46", "text": "The phorbol ester , PMA , was also a potent inducer of Fos kinase activity in all of the above populations , suggesting that PKC plays a role in the regulation of this enzyme .", "annotated_text": "The phorbol ester , PMA , was also a potent inducer of <protein>Fos kinase</protein> activity in all of the above populations , suggesting that <protein>PKC</protein> plays a role in the regulation of this <protein>enzyme</protein> ."}48{"id": "47", "text": "Fos kinase phosphorylates c-Fos at a site near the C-terminus , as well as a peptide derived from this region ( residues 359-370 , RKGSSSNEPSSD ) , and Fos peptide competitively inhibited c-Fos phosphorylation .", "annotated_text": "<protein>Fos kinase</protein> phosphorylates <protein>c-Fos</protein> at a site near the <protein>C-terminus</protein> , as well as a peptide derived from this region ( <protein>residues 359-370</protein> , <protein>RKGSSSNEPSSD</protein> ) , and Fos peptide competitively inhibited <protein>c-Fos</protein> phosphorylation ."}49{"id": "48", "text": "Fos kinase was shown to be distinct from other identified serine/threonine kinases , including protein kinase A , protein kinase C , casein kinase II , MAP kinases , p70S6K and p90RSK .", "annotated_text": "<protein>Fos kinase</protein> was shown to be distinct from other identified <protein>serine/threonine kinases</protein> , including <protein>protein kinase A</protein> , <protein>protein kinase C</protein> , <protein>casein kinase II</protein> , <protein>MAP kinases</protein> , <protein>p70S6K</protein> and <protein>p90RSK</protein> ."}50{"id": "49", "text": "Fos kinase was purified by anion exchange chromatography and exhibited an apparent M ( r ) = 65 , 000 and isoelectric point = 6.1 .", "annotated_text": "<protein>Fos kinase</protein> was purified by anion exchange chromatography and exhibited an apparent M ( r ) = 65 , 000 and isoelectric point = 6.1 ."}51{"id": "50", "text": "Fos kinase may play a role in transcriptional regulation through its capacity to phosphorylate c-Fos at a site required for expression of the transcriptional transrepressive activity of this molecule .", "annotated_text": "<protein>Fos kinase</protein> may play a role in transcriptional regulation through its capacity to phosphorylate <protein>c-Fos</protein> at a site required for expression of the transcriptional transrepressive activity of this molecule ."}52{"id": "51", "text": "Moreover , its rapid activation suggests it may have a wider role within signal transduction cascades in lymphocytes .", "annotated_text": "Moreover , its rapid activation suggests it may have a wider role within signal transduction cascades in <cell_type>lymphocytes</cell_type> ."}53{"id": "52", "text": "Antigenic specificities of human CD4+ T-cell clones recovered from recurrent genital herpes simplex virus type 2 lesions .", "annotated_text": "Antigenic specificities of <cell_line>human CD4+ T-cell clones</cell_line> recovered from recurrent genital herpes simplex virus type 2 lesions ."}54{"id": "53", "text": "Lesions resulting from recurrent genital herpes simplex virus ( HSV ) infection are characterized by infiltration of CD4+ lymphocytes .", "annotated_text": "Lesions resulting from recurrent genital herpes simplex virus ( HSV ) infection are characterized by infiltration of <cell_type>CD4+ lymphocytes</cell_type> ."}55{"id": "54", "text": "We have investigated the antigenic specificity of 47 HSV-specific CD4+ T-cell clones recovered from the HSV-2 buttock and thigh lesions of five patients .", "annotated_text": "We have investigated the antigenic specificity of 47 <cell_line>HSV-specific CD4+ T-cell clones</cell_line> recovered from the HSV-2 buttock and thigh lesions of five patients ."}56{"id": "55", "text": "Clones with proliferative responses to recombinant truncated glycoprotein B ( gB ) or gD of HSV-2 or purified natural gC of HSV-2 comprised a minority of the total number of HSV-specific clones isolated from lesions .", "annotated_text": "Clones with proliferative responses to <protein>recombinant truncated glycoprotein B</protein> ( <protein>gB</protein> ) or <protein>gD</protein> of HSV-2 or purified natural gC of HSV-2 comprised a minority of the total number of <cell_line>HSV-specific clones</cell_line> isolated from lesions ."}57{"id": "56", "text": "The gC2- and gD2-specific CD4+ clones had cytotoxic activity .", "annotated_text": "The <cell_line>gC2- and gD2-specific CD4+ clones</cell_line> had cytotoxic activity ."}58{"id": "57", "text": "The approximate locations of the HSV-2 genes encoding HSV-2 type-specific CD4+ antigens have been determined by using HSV-1 x HSV-2 intertypic recombinant virus and include the approximate map regions 0.30 to 0.46 , 0.59 to 0.67 , 0.67 to 0.73 , and 0.82 to 1.0 units .", "annotated_text": "The approximate locations of the HSV-2 genes encoding HSV-2 type-specific <protein>CD4+ antigens</protein> have been determined by using HSV-1 x HSV-2 intertypic recombinant virus and include the approximate map regions 0.30 to 0.46 , 0.59 to 0.67 , 0.67 to 0.73 , and 0.82 to 1.0 units ."}59{"id": "58", "text": "The antigenic specificity of an HLA DQ2-restricted , HSV-2 type-specific T-cell clone was mapped to amino acids 425 to 444 of VP16 of HSV-2 by sequential use of an intertypic recombinant virus containing VP16 of HSV-2 in an HSV-1 background , recombinant VP16 fusion proteins , and synthetic peptides .", "annotated_text": "The antigenic specificity of an <cell_line>HLA DQ2-restricted , HSV-2 type-specific T-cell clone</cell_line> was mapped to <protein>amino acids 425 to 444</protein> of <protein>VP16</protein> of HSV-2 by sequential use of an intertypic recombinant virus containing <protein>VP16</protein> of HSV-2 in an HSV-1 background , <protein>recombinant VP16 fusion proteins</protein> , and synthetic peptides ."}60{"id": "59", "text": "Each of the remaining four patients also yielded at least one type-specific T-cell clone reactive with an HSV-2 epitope mapping to approximately 0.67 to 0.73 map units .", "annotated_text": "Each of the remaining four patients also yielded at least one <cell_line>type-specific T-cell clone</cell_line> reactive with an HSV-2 epitope mapping to approximately 0.67 to 0.73 map units ."}61{"id": "60", "text": "The antigenic specificities of lesion-derived CD4+ T-cell clones are quite diverse and include at least 10 epitopes .", "annotated_text": "The antigenic specificities of <cell_line>lesion-derived CD4+ T-cell clones</cell_line> are quite diverse and include at least 10 epitopes ."}62{"id": "61", "text": "Human T-cell clones reactive with gC and VP16 are reported here for the first time .", "annotated_text": "<cell_line>Human T-cell clones</cell_line> reactive with <protein>gC</protein> and <protein>VP16</protein> are reported here for the first time ."}63{"id": "62", "text": "Marked basophilia in acute promyelocytic leukaemia treated with all-trans retinoic acid : molecular analysis of the cell origin of the basophils .", "annotated_text": "Marked basophilia in acute promyelocytic leukaemia treated with all-trans retinoic acid : molecular analysis of the cell origin of the <cell_type>basophils</cell_type> ."}64{"id": "63", "text": "We report a patient with acute promyelocytic leukaemia who developed marked basophilia during all-trans retinoic acid treatment .", "annotated_text": "We report a patient with acute promyelocytic leukaemia who developed marked basophilia during all-trans retinoic acid treatment ."}65{"id": "64", "text": "We studied genomic DNA and RNA extracted from the patient 's peripheral leucocytes in order to determine the origin of the basophils .", "annotated_text": "We studied <dna>genomic DNA</dna> and RNA extracted from the patient 's <cell_type>peripheral leucocytes</cell_type> in order to determine the origin of the <cell_type>basophils</cell_type> ."}66{"id": "65", "text": "The RAR alpha rearranged band in the Southern blot analysis and a chimaeric product of PML-RAR alpha by polymerase chain reaction were strongly visible before ATRA treatment , but at the time of maximal basophilia both of them were markedly diminished .", "annotated_text": "The <protein>RAR alpha</protein> rearranged band in the Southern blot analysis and a <protein>chimaeric product</protein> of <protein>PML-RAR alpha</protein> by polymerase chain reaction were strongly visible before ATRA treatment , but at the time of maximal basophilia both of them were markedly diminished ."}67{"id": "66", "text": "These findings suggest that the basophils which appeared during the ATRA treatment are reactive in nature rather than a leukaemic clone .", "annotated_text": "These findings suggest that the <cell_type>basophils</cell_type> which appeared during the ATRA treatment are reactive in nature rather than a <cell_line>leukaemic clone</cell_line> ."}68{"id": "67", "text": "Activation of the interleukin 6 gene by Mycobacterium tuberculosis or lipopolysaccharide is mediated by nuclear factors NF-IL6 and NF-kappa B [ published erratum appears in Proc Natl Acad Sci U S A 1995 Apr 11 ; 92 ( 8 ) : 3632 ]", "annotated_text": "Activation of the <dna>interleukin 6 gene</dna> by Mycobacterium tuberculosis or lipopolysaccharide is mediated by <protein>nuclear factors NF-IL6</protein> and <protein>NF-kappa B</protein> [ published erratum appears in Proc Natl Acad Sci U S A 1995 Apr 11 ; 92 ( 8 ) : 3632 ]"}69{"id": "68", "text": "The host response to Mycobacterium tuberculosis includes granuloma formation at sites of infection and systemic symptoms .", "annotated_text": "The host response to Mycobacterium tuberculosis includes granuloma formation at sites of infection and systemic symptoms ."}70{"id": "69", "text": "Cytokines have been identified by immunohistochemistry in granulomas in animal models of bacillus Calmette-Guerin ( BCG ) infection and are released by mononuclear phagocytes upon stimulation by mycobacterial proteins .", "annotated_text": "<protein>Cytokines</protein> have been identified by immunohistochemistry in granulomas in animal models of bacillus Calmette-Guerin ( BCG ) infection and are released by <cell_type>mononuclear phagocytes</cell_type> upon stimulation by mycobacterial proteins ."}71{"id": "70", "text": "In this regard , the cytokine interleukin 6 ( IL-6 ) may play a role in the clinical manifestations and pathological events of tuberculosis infection .", "annotated_text": "In this regard , the <protein>cytokine</protein> <protein>interleukin 6</protein> ( <protein>IL-6</protein> ) may play a role in the clinical manifestations and pathological events of tuberculosis infection ."}72{"id": "71", "text": "We have demonstrated that lipoarabinomannan ( LAM ) from the mycobacterial cell wall , which was virtually devoid of lipopolysaccharide ( LPS ) , stimulated mononuclear phagocytes to release IL-6 in a dose-response manner .", "annotated_text": "We have demonstrated that <protein>lipoarabinomannan</protein> ( <protein>LAM</protein> ) from the mycobacterial cell wall , which was virtually devoid of lipopolysaccharide ( LPS ) , stimulated <cell_type>mononuclear phagocytes</cell_type> to release <protein>IL-6</protein> in a dose-response manner ."}73{"id": "72", "text": "LAM and LPS were potent inducers of IL-6 gene expression in peripheral blood monocytes .", "annotated_text": "<protein>LAM</protein> and LPS were potent inducers of <dna>IL-6 gene</dna> expression in <cell_type>peripheral blood monocytes</cell_type> ."}74{"id": "73", "text": "Both LAM -and LPS-inducible IL-6 promoter activity was localized to a DNA fragment , positions -158 to -49 , by deletion analysis and chloramphenicol acetyltransferase assay .", "annotated_text": "Both <protein>LAM</protein> -and <dna>LPS-inducible IL-6 promoter</dna> activity was localized to a <dna>DNA fragment</dna> , positions <dna>-158 to -49</dna> , by deletion analysis and <protein>chloramphenicol acetyltransferase</protein> assay ."}75{"id": "74", "text": "Two nuclear factor NF-IL6 ( positions -153 to -145 and -83 to -75 ) and one nuclear factor NF-kappa B ( positions -72 to -63 ) motifs are present within this fragment .", "annotated_text": "Two <protein>nuclear factor NF-IL6</protein> ( positions <dna>-153 to -145</dna> and -83 to -75 ) and one <dna>nuclear factor NF-kappa B ( positions -72 to -63 ) motifs</dna> are present within this fragment ."}76{"id": "75", "text": "Site-directed mutagenesis of one or more of these motifs within the IL-6 promoter demonstrated that each has positive regulatory activity and that they could act in a function- and orientation-independent manner .", "annotated_text": "Site-directed mutagenesis of one or more of these motifs within the <protein>IL-6</protein> promoter demonstrated that each has positive regulatory activity and that they could act in a function- and orientation-independent manner ."}77{"id": "76", "text": "Deletion of all three elements abolished inducibility of IL-6 promoter activity by both LAM and LPS .", "annotated_text": "Deletion of all three elements abolished inducibility of <dna>IL-6 promoter</dna> activity by both <protein>LAM</protein> and LPS ."}78{"id": "77", "text": "We conclude that the NF-IL6 and NF-kappa B sites mediate IL-6 induction in response to both LPS and LAM , acting as bacterial or mycobacterial response elements .", "annotated_text": "We conclude that the <dna>NF-IL6 and NF-kappa B sites</dna> mediate <protein>IL-6</protein> induction in response to both LPS and <protein>LAM</protein> , acting as <dna>bacterial or mycobacterial response elements</dna> ."}79{"id": "78", "text": "Regulation of CD14 expression during monocytic differentiation induced with 1 alpha , 25-dihydroxyvitamin D3 .", "annotated_text": "Regulation of <protein>CD14</protein> expression during monocytic differentiation induced with 1 alpha , 25-dihydroxyvitamin D3 ."}80{"id": "79", "text": "CD14 , a monocyte/macrophage receptor for the complex of LPS and LPS binding protein , is a differentiation marker for the monocyte/macrophage lineage .", "annotated_text": "<protein>CD14</protein> , a <protein>monocyte/macrophage receptor</protein> for the complex of LPS and <protein>LPS binding protein</protein> , is a differentiation marker for the <cell_type>monocyte/macrophage lineage</cell_type> ."}81{"id": "80", "text": "We have analyzed the regulation of CD14 expression during 1 alpha , 25-dihydroxyvitamin D3 ( VitD3 ) -induced monocytic differentiation .", "annotated_text": "We have analyzed the regulation of <protein>CD14</protein> expression during 1 alpha , 25-dihydroxyvitamin D3 ( VitD3 ) -induced monocytic differentiation ."}82{"id": "81", "text": "Using FACS , Northern blotting , and nuclear run-on analyses , we demonstrate that the up-regulation of CD14 expression during monocytic cell maturation is regulated mainly at the level of gene transcription , and that new protein synthesis is required for CD14 induction .", "annotated_text": "Using FACS , Northern blotting , and nuclear run-on analyses , we demonstrate that the up-regulation of <protein>CD14</protein> expression during monocytic cell maturation is regulated mainly at the level of gene transcription , and that new protein synthesis is required for <protein>CD14</protein> induction ."}83{"id": "82", "text": "We have recently cloned the CD14 5 ' upstream sequence and demonstrated its tissue-specific promoter activity .", "annotated_text": "We have recently cloned the <dna>CD14 5 ' upstream sequence</dna> and demonstrated its <dna>tissue-specific promoter</dna> activity ."}84{"id": "83", "text": "Using stable transfection of the monocytoid U937 cell line with a series of deletion mutants of the CD14 5 ' upstream sequence coupled to a reporter gene construct , we show that bp -128 to -70 is the critical region for the induction of CD14 expression .", "annotated_text": "Using stable transfection of the <cell_line>monocytoid U937 cell line</cell_line> with a series of deletion mutants of the <dna>CD14 5 ' upstream sequence</dna> coupled to a reporter gene construct , we show that <dna>bp -128 to -70</dna> is the critical region for the induction of <protein>CD14</protein> expression ."}85{"id": "84", "text": "This region contains two binding sites for the Sp1 transcription factor .", "annotated_text": "This region contains two <dna>binding sites</dna> for the <protein>Sp1 transcription factor</protein> ."}86{"id": "85", "text": "A 3-bp mutation at the distal Sp1-binding site not only eliminates Sp1 interaction , but also abolishes most of the VitD3 induction of CD14 expression .", "annotated_text": "A 3-bp mutation at the distal <dna>Sp1-binding site</dna> not only eliminates <protein>Sp1</protein> interaction , but also abolishes most of the VitD3 induction of <protein>CD14</protein> expression ."}87{"id": "86", "text": "Electrophoretic mobility shift analysis does not detect a direct interaction of the CD14 distal Sp1-binding site with the vitamin D3 receptor and its partner , the retinoid X receptor .", "annotated_text": "Electrophoretic mobility shift analysis does not detect a direct interaction of the <protein>CD14</protein> distal <dna>Sp1-binding site</dna> with the <protein>vitamin D3 receptor</protein> and its partner , the <protein>retinoid X receptor</protein> ."}88{"id": "87", "text": "These data demonstrate that VitD3 induces CD14 indirectly through some intermediary factor , and suggest a critical role for Sp1 in this process .", "annotated_text": "These data demonstrate that VitD3 induces <protein>CD14</protein> indirectly through some <protein>intermediary factor</protein> , and suggest a critical role for <protein>Sp1</protein> in this process ."}89{"id": "88", "text": "DNA-binding and transcriptional regulatory properties of hepatic leukemia factor ( HLF ) and the t ( 17 ; 19 ) acute lymphoblastic leukemia chimera E2A-HLF .", "annotated_text": "DNA-binding and transcriptional regulatory properties of <protein>hepatic leukemia factor</protein> ( <protein>HLF</protein> ) and the t ( 17 ; 19 ) <protein>acute lymphoblastic leukemia chimera E2A-HLF</protein> ."}90{"id": "89", "text": "The t ( 17 ; 19 ) translocation in acute lymphoblastic leukemias results in creation of E2A-hepatic leukemia factor ( HLF ) chimeric proteins that contain the DNA-binding and protein dimerization domains of the basic leucine zipper ( bZIP ) protein HLF fused to a portion of E2A proteins with transcriptional activation properties .", "annotated_text": "The <dna>t ( 17 ; 19 )</dna> translocation in acute lymphoblastic leukemias results in creation of <protein>E2A-hepatic leukemia factor</protein> ( <protein>HLF</protein> ) <protein>chimeric proteins</protein> that contain the <protein>DNA-binding and protein dimerization domains</protein> of the <protein>basic leucine zipper ( bZIP ) protein</protein> <protein>HLF</protein> fused to a portion of <protein>E2A proteins</protein> with transcriptional activation properties ."}91{"id": "90", "text": "An in vitro binding site selection procedure was used to determine DNA sequences preferentially bound by wild-type HLF and chimeric E2A-HLF proteins isolated from various t ( 17 ; 19 ) -bearing leukemias .", "annotated_text": "An in vitro binding site selection procedure was used to determine DNA sequences preferentially bound by <protein>wild-type HLF</protein> and <protein>chimeric E2A-HLF</protein> proteins isolated from various <cell_line>t ( 17 ; 19 ) -bearing leukemias</cell_line> ."}92{"id": "91", "text": "All were found to selectively bind the consensus sequence 5'-GTTACGTAAT-3 ' with high affinity .", "annotated_text": "All were found to selectively bind the <dna>consensus sequence</dna> 5'-GTTACGTAAT-3 ' with high affinity ."}93{"id": "92", "text": "Wild-type and chimeric HLF proteins also bound closely related sites identified previously for bZIP proteins of both the proline -and acidic amino acid-rich ( PAR ) and C/EBP subfamilies ; however , E2A-HLF proteins were significantly less tolerant of certain deviations from the HLF consensus binding site .", "annotated_text": "Wild-type and <protein>chimeric HLF proteins</protein> also bound closely related sites identified previously for <protein>bZIP proteins</protein> of both the <protein>proline</protein> -and acidic amino acid-rich ( <protein>PAR</protein> ) and <protein>C/EBP subfamilies</protein> ; however , <protein>E2A-HLF</protein> proteins were significantly less tolerant of certain deviations from the <dna>HLF consensus binding site</dna> ."}94{"id": "93", "text": "These differences were directly attributable to loss of an HLF ancillary DNA-binding domain in all E2A-HLF chimeras and were further exacerbated by a zipper mutation in one isolate .", "annotated_text": "These differences were directly attributable to loss of an <dna>HLF ancillary DNA-binding domain</dna> in all <protein>E2A-HLF chimeras</protein> and were further exacerbated by a zipper mutation in one isolate ."}95{"id": "94", "text": "Both wild-type and chimeric HLF proteins displayed transcriptional activator properties in lymphoid and nonlymphoid cells on reporter genes containing HLF or C/EBP consensus binding sites .", "annotated_text": "Both <protein>wild-type</protein> and <protein>chimeric HLF proteins</protein> displayed <protein>transcriptional activator</protein> properties in <cell_type>lymphoid and nonlymphoid cells</cell_type> on <dna>reporter genes</dna> containing <dna>HLF or C/EBP consensus binding sites</dna> ."}96{"id": "95", "text": "But on reporter genes with nonoptimal binding sites , their transcriptional properties diverged and E2A-HLF competitively inhibited activation by wild-type PAR proteins .", "annotated_text": "But on <dna>reporter genes</dna> with <dna>nonoptimal binding sites</dna> , their transcriptional properties diverged and <protein>E2A-HLF</protein> competitively inhibited activation by <protein>wild-type PAR proteins</protein> ."}97{"id": "96", "text": "These findings establish a spectrum of binding site-specific transcriptional properties for E2A-HLF which may preferentially activate expression of select subordinate genes as a homodimer and potentially antagonize expression of others through heteromeric interactions .", "annotated_text": "These findings establish a spectrum of binding site-specific transcriptional properties for <protein>E2A-HLF</protein> which may preferentially activate expression of select subordinate genes as a homodimer and potentially antagonize expression of others through heteromeric interactions ."}98{"id": "97", "text": "ZAP-70 tyrosine kinase , CD45 , and T cell receptor involvement in UV- and H2O2-induced T cell signal transduction .", "annotated_text": "<protein>ZAP-70 tyrosine kinase</protein> , <protein>CD45</protein> , and <protein>T cell receptor</protein> involvement in UV- and H2O2-induced T cell signal transduction ."}99{"id": "98", "text": "Several mammalian responses to UV irradiation , including the activation of NF-kappa B , are believed to involve tyrosine phosphorylation .", "annotated_text": "Several mammalian responses to UV irradiation , including the activation of <protein>NF-kappa B</protein> , are believed to involve tyrosine phosphorylation ."}100{"id": "99", "text": "UV irradiation and H2O2 treatment of T lymphocytes induce protein tyrosine phosphorylation and Ca2+ signals similar to those observed following biological stimulation .", "annotated_text": "UV irradiation and H2O2 treatment of <cell_type>T lymphocytes</cell_type> induce protein tyrosine phosphorylation and Ca2+ signals similar to those observed following biological stimulation ."}101{"id": "100", "text": "We have examined the role of cell surface molecules in these responses .", "annotated_text": "We have examined the role of cell surface molecules in these responses ."}102{"id": "101", "text": "Normal T lymphocytes whose surface expression of CD3 was depleted showed impaired UV-induced tyrosine phosphorylation and Ca2+ signals .", "annotated_text": "Normal <cell_type>T lymphocytes</cell_type> whose surface expression of <protein>CD3</protein> was depleted showed impaired UV-induced tyrosine phosphorylation and Ca2+ signals ."}103{"id": "102", "text": "Similarly , Jurkat T cell lines deficient in CD3 or CD45 expression also gave impaired UV responses .", "annotated_text": "Similarly , <cell_line>Jurkat T cell lines</cell_line> deficient in CD3 or CD45 expression also gave impaired UV responses ."}104{"id": "103", "text": "However , all these cell types still gave strong Ca2+ and tyrosine phosphorylation responses to H2O2 .", "annotated_text": "However , all these cell types still gave strong Ca2+ and tyrosine phosphorylation responses to H2O2 ."}105{"id": "104", "text": "The T cell tyrosine kinase ZAP-70 was found to be highly responsive to UV and H2O2 treatment .", "annotated_text": "The T cell tyrosine <protein>kinase ZAP-70</protein> was found to be highly responsive to UV and H2O2 treatment ."}106{"id": "105", "text": "ZAP-70 responsiveness to UV required expression of both CD3 and CD45 , whereas only CD3 was required for the response to H2O2 .", "annotated_text": "<protein>ZAP-70</protein> responsiveness to UV required expression of both <protein>CD3</protein> and <protein>CD45</protein> , whereas only <protein>CD3</protein> was required for the response to H2O2 ."}107{"id": "106", "text": "UV-induced activation of NF-kappa B was blocked by CD3 depletion , indicating the importance of such cell surface molecules in biological responses to UV .", "annotated_text": "UV-induced activation of <protein>NF-kappa B</protein> was blocked by <protein>CD3</protein> depletion , indicating the importance of such <protein>cell surface molecules</protein> in biological responses to UV ."}108{"id": "107", "text": "In nonlymphoid cells , the epidermal growth factor receptor displayed increased tyrosine phosphorylation within seconds of UV irradiation .", "annotated_text": "In <cell_type>nonlymphoid cells</cell_type> , the <protein>epidermal growth factor receptor</protein> displayed increased tyrosine phosphorylation within seconds of UV irradiation ."}109{"id": "108", "text": "These results suggest that UV-induced signal transduction is mediated via cell surface receptors that normally respond to biological stimulation , whereas H2O2 is able to partially bypass this requirement .", "annotated_text": "These results suggest that UV-induced signal transduction is mediated via <protein>cell surface receptors</protein> that normally respond to biological stimulation , whereas H2O2 is able to partially bypass this requirement ."}110{"id": "109", "text": "Inhibition of the differentiation of human myeloid cell lines by redox changes induced through glutathione depletion .", "annotated_text": "Inhibition of the differentiation of <cell_line>human myeloid cell lines</cell_line> by redox changes induced through glutathione depletion ."}111{"id": "110", "text": "We have investigated the effect of redox changes in vivo on the differentiation of two human myeloid cell lines , HL-60 and KG-1 .", "annotated_text": "We have investigated the effect of redox changes in vivo on the differentiation of two <cell_line>human myeloid cell lines</cell_line> , <cell_line>HL-60</cell_line> and <cell_line>KG-1</cell_line> ."}112{"id": "111", "text": "The glutathione-depleting agent diethyl maleate ( DEM ) prevented the development of differentiated features in response to phorbol esters , including adherence of the cells to plastic surfaces and repression of the myeloperoxidase and CD34 genes .", "annotated_text": "The glutathione-depleting agent diethyl maleate ( DEM ) prevented the development of differentiated features in response to phorbol esters , including adherence of the cells to plastic surfaces and repression of the <dna>myeloperoxidase and CD34 genes</dna> ."}113{"id": "112", "text": "Moreover , DEM abolished phorbol 12-myristate 13-acetate-induced activation of the transcription factors AP-1 and Egr-1 , suggesting that inhibition of differentiation may be due , at least in part , to redox modifications of these proteins .", "annotated_text": "Moreover , DEM abolished phorbol 12-myristate 13-acetate-induced activation of the <protein>transcription factors</protein> <protein>AP-1</protein> and <protein>Egr-1</protein> , suggesting that inhibition of differentiation may be due , at least in part , to redox modifications of these <protein>proteins</protein> ."}114{"id": "113", "text": "Lipopolysaccharide induction of tissue factor gene expression in monocytic cells is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site .", "annotated_text": "Lipopolysaccharide induction of <dna>tissue factor gene</dna> expression in <cell_type>monocytic cells</cell_type> is mediated by binding of <protein>c-Rel/p65 heterodimers</protein> to a <dna>kappa B-like site</dna> ."}115{"id": "114", "text": "Exposure of monocytic cells to bacterial lipopolysaccharide ( LPS ) activates the NF-kappa B/Rel family of proteins and leads to the rapid induction of inflammatory gene products , including tissue factor ( TF ) .", "annotated_text": "Exposure of <cell_type>monocytic cells</cell_type> to bacterial lipopolysaccharide ( LPS ) activates the <protein>NF-kappa B/Rel family</protein> of proteins and leads to the rapid induction of <protein>inflammatory gene products</protein> , including <protein>tissue factor</protein> ( <protein>TF</protein> ) ."}116{"id": "115", "text": "TF is the primary cellular initiator of the coagulation protease cascades .", "annotated_text": "<protein>TF</protein> is the primary cellular initiator of the <protein>coagulation protease</protein> cascades ."}117{"id": "116", "text": "Here we report the characterization of a nuclear complex from human monocytic cells that bound to a kappa B-like site , 5'-CGGAGTTTCC-3 ' , in the 5'-flanking region of the human TF gene .", "annotated_text": "Here we report the characterization of a <protein>nuclear complex</protein> from human <cell_type>monocytic cells</cell_type> that bound to a <dna>kappa B-like site</dna> , <dna>5'-CGGAGTTTCC-3 '</dna> , in the <dna>5'-flanking region</dna> of the <dna>human TF gene</dna> ."}118{"id": "117", "text": "This nuclear complex was activated by LPS with kinetics that preceded induction of the TF gene .", "annotated_text": "This <protein>nuclear complex</protein> was activated by LPS with kinetics that preceded induction of the <dna>TF gene</dna> ."}119{"id": "118", "text": "In vitro binding studies demonstrated that the TF site bound translated c-Rel and p65 homodimers but not p50/p65 heterodimers or p50 homodimers .", "annotated_text": "In vitro binding studies demonstrated that the <dna>TF site</dna> bound translated <protein>c-Rel and p65 homodimers</protein> but not <protein>p50/p65 heterodimers</protein> or <protein>p50 homodimers</protein> ."}120{"id": "119", "text": "Base-pair substitutions in the TF site indicated that the presence of a cytosine at position 1 precluded binding of NF-kappa B .", "annotated_text": "Base-pair substitutions in the <dna>TF site</dna> indicated that the presence of a cytosine at <protein>position 1</protein> precluded binding of <protein>NF-kappa B</protein> ."}121{"id": "120", "text": "In fact , under low-ionic-strength conditions , the TF complex did not migrate with translated p50/p65 dimers but instead comigrated with c-Rel/p65 dimers .", "annotated_text": "In fact , under low-ionic-strength conditions , the <protein>TF complex</protein> did not migrate with translated <protein>p50/p65 dimers</protein> but instead comigrated with <protein>c-Rel/p65 dimers</protein> ."}122{"id": "121", "text": "Antibodies against the NF-kappa B and Rel proteins and UV cross-linking studies revealed the presence of c-Rel and p65 and the absence of p50 in the TF complex and further showed that c-Rel/p65 heterodimers selectively bound to the TF kappa B-like site .", "annotated_text": "Antibodies against the <protein>NF-kappa B</protein> and Rel proteins and UV cross-linking studies revealed the presence of <protein>c-Rel</protein> and p65 and the absence of <protein>p50</protein> in the <protein>TF complex</protein> and further showed that <protein>c-Rel/p65 heterodimers</protein> selectively bound to the <dna>TF kappa B-like site</dna> ."}123{"id": "122", "text": "Functional studies indicated that the TF site conferred LPS inducibility on a heterologous promoter and was transactivated by c-Rel or p65 .", "annotated_text": "Functional studies indicated that the <dna>TF site</dna> conferred LPS inducibility on a <dna>heterologous promoter</dna> and was transactivated by <protein>c-Rel</protein> or p65 ."}124{"id": "123", "text": "Taken together , our results demonstrated that binding of c-Rel/p65 heterodimers to a novel kappa B-like site mediated LPS induction of TF gene expression in monocytic cells .", "annotated_text": "Taken together , our results demonstrated that binding of <protein>c-Rel/p65 heterodimers</protein> to a novel <dna>kappa B-like site</dna> mediated LPS induction of <protein>TF</protein> gene expression in <cell_type>monocytic cells</cell_type> ."}125{"id": "124", "text": "Inhibition of T cell activation by the extracellular matrix protein tenascin .", "annotated_text": "Inhibition of T cell activation by the <protein>extracellular matrix protein</protein> <protein>tenascin</protein> ."}126{"id": "125", "text": "Tenascin ( TN ) is an extracellular matrix protein that is expressed widely in the fetus and sparingly in the adult , but reappears at high levels in certain areas of tissue insult such as tumor matrices and sites of wound healing .", "annotated_text": "<protein>Tenascin</protein> ( <protein>TN</protein> ) is an <protein>extracellular matrix protein</protein> that is expressed widely in the fetus and sparingly in the adult , but reappears at high levels in certain areas of tissue insult such as tumor matrices and sites of wound healing ."}127{"id": "126", "text": "We show here that soluble TN inhibits proliferation of human T cells in response to alpha CD3 Ab co-immobilized with the extracellular matrix protein fibronectin ( FN ) .", "annotated_text": "We show here that soluble <protein>TN</protein> inhibits proliferation of <cell_type>human T cells</cell_type> in response to <protein>alpha CD3 Ab</protein> co-immobilized with the <protein>extracellular matrix protein</protein> <protein>fibronectin</protein> ( <protein>FN</protein> ) ."}128{"id": "127", "text": "TN also inhibits proliferation driven by alpha CD3/IL-2 or by phorbol ester/IL-2 , and it prevents high level induction of IL-2R .", "annotated_text": "<protein>TN</protein> also inhibits proliferation driven by <protein>alpha CD3/IL-2</protein> or by <protein>phorbol ester/IL-2 ,</protein> and it prevents high level induction of <protein>IL-2R</protein> ."}129{"id": "128", "text": "The presence of TN in culture medium does not detectably alter the pattern of tyrosine phosphorylation resulting from T cell triggering with alpha CD3 , but at later time points prevents the appearance of functional NF-AT1 transcription factor complexes in T cell nuclear extracts .", "annotated_text": "The presence of <protein>TN</protein> in culture medium does not detectably alter the pattern of tyrosine phosphorylation resulting from T cell triggering with <protein>alpha CD3</protein> , but at later time points prevents the appearance of functional <protein>NF-AT1 transcription factor complexes</protein> in T cell nuclear extracts ."}130{"id": "129", "text": "These findings are consistent with the postulated role for TN as a natural antagonist to FN action , and suggest that T cell responses occurring at tissue sites in which TN is expressed could be influenced by its presence .", "annotated_text": "These findings are consistent with the postulated role for <protein>TN</protein> as a natural antagonist to <protein>FN</protein> action , and suggest that T cell responses occurring at tissue sites in which <protein>TN</protein> is expressed could be influenced by its presence ."}131{"id": "130", "text": "Human immunodeficiency virus type 1 Nef protein down-regulates transcription factors NF-kappa B and AP-1 in human T cells in vitro after T-cell receptor stimulation .", "annotated_text": "Human immunodeficiency virus type 1 Nef protein down-regulates <protein>transcription factors</protein> <protein>NF-kappa B</protein> and <protein>AP-1</protein> in <cell_type>human T cells</cell_type> in vitro after T-cell receptor stimulation ."}132{"id": "131", "text": "Human immunodeficiency virus type 1 ( HIV-1 ) negative factor ( Nef ) has been shown to down-regulate the transcription factors NF-kappa B and AP-1 in vitro .", "annotated_text": "Human immunodeficiency virus type 1 ( HIV-1 ) <protein>negative factor</protein> ( <protein>Nef</protein> ) has been shown to down-regulate the <protein>transcription factors</protein> <protein>NF-kappa B</protein> and <protein>AP-1</protein> in vitro ."}133{"id": "132", "text": "To define the mechanism of action of the Nef protein , the signal transduction pathways which may be affected in T cells by constitutive expression of the nef gene were examined .", "annotated_text": "To define the mechanism of action of the <protein>Nef</protein> protein , the signal transduction pathways which may be affected in <cell_type>T cells</cell_type> by constitutive expression of the nef gene were examined ."}134{"id": "133", "text": "Stimulation of T cells with tumor necrosis factor , interleukin-1 , or lipopolysaccharide resulted in the recruitment of transcriptional factors to a similar level whether or not the cells expressed the nef gene .", "annotated_text": "Stimulation of <cell_type>T cells</cell_type> with tumor necrosis factor , interleukin-1 , or lipopolysaccharide resulted in the recruitment of transcriptional factors to a similar level whether or not the cells expressed the nef gene ."}135{"id": "134", "text": "On the other hand , stimulation of T cells by mitogens or antibodies to the T-cell receptor ( TCR ) - CD3 complex resulted in the down-regulation of transcriptional factors NF-kappa B and AP-1 in cells expressing the nef gene compared with cells not expressing the nef gene .", "annotated_text": "On the other hand , stimulation of <cell_type>T cells</cell_type> by mitogens or antibodies to the T-cell receptor ( TCR ) - <protein>CD3</protein> complex resulted in the down-regulation of transcriptional factors <protein>NF-kappa B</protein> and <protein>AP-1</protein> in cells expressing the nef gene compared with cells not expressing the nef gene ."}136{"id": "135", "text": "Because the Nef protein does not affect the surface expression of the CD3 -TCR complex , we conclude that the Nef protein down-regulates the transcriptional factors NF-kappa B and AP-1 in T cells in vitro through an effect on the TCR-dependent signal transduction pathway .", "annotated_text": "Because the <protein>Nef</protein> protein does not affect the surface expression of the <protein>CD3</protein> -TCR complex , we conclude that the <protein>Nef</protein> protein down-regulates the transcriptional factors <protein>NF-kappa B</protein> and <protein>AP-1</protein> in <cell_type>T cells</cell_type> in vitro through an effect on the TCR-dependent signal transduction pathway ."}137{"id": "136", "text": "Effects of alpha-lipoic acid and dihydrolipoic acid on expression of proto-oncogene c-fos .", "annotated_text": "Effects of alpha-lipoic acid and dihydrolipoic acid on expression of <dna>proto-oncogene c-fos</dna> ."}138{"id": "137", "text": "The transcription factor AP-1 is an important human mediator of the cellular response to serum , growth factors , and phorbol esters such as 12-O-tetradecanoyl-phorbol-13 acetate ( TPA ) .", "annotated_text": "The <protein>transcription factor</protein> <protein>AP-1</protein> is an important human mediator of the cellular response to serum , <protein>growth factors</protein> , and phorbol esters such as 12-O-tetradecanoyl-phorbol-13 acetate ( TPA ) ."}139{"id": "138", "text": "The AP-1 complex consists of distinct protein heterodimers encoded by the proto-oncogene c-fos and c-jun mRNA whose gene expression can be induced by TPA , cyclic AMP and growth factors .", "annotated_text": "The <protein>AP-1</protein> complex consists of distinct <protein>protein heterodimers</protein> encoded by the <dna>proto-oncogene c-fos</dna> and <rna>c-jun mRNA</rna> whose gene expression can be induced by TPA , cyclic AMP and <protein>growth factors</protein> ."}140{"id": "139", "text": "Recent findings suggest an involvement of reactive oxygen species in the pathway of TPA and protein kinase C leading to expression of c-fos and c-jun mRNA .", "annotated_text": "Recent findings suggest an involvement of reactive oxygen species in the pathway of TPA and <protein>protein kinase C</protein> leading to expression of <rna>c-fos and c-jun mRNA</rna> ."}141{"id": "140", "text": "To investigate the role of reactive oxygen species we studied the effects of alpha-lipoic acid and dihydrolipoic acid ( natural thiol antioxidants ) on the expression of c-fos mRNA in human Jurkat T cells .", "annotated_text": "To investigate the role of reactive oxygen species we studied the effects of alpha-lipoic acid and dihydrolipoic acid ( natural thiol antioxidants ) on the expression of <rna>c-fos mRNA</rna> in <cell_line>human Jurkat T cells</cell_line> ."}142{"id": "141", "text": "When cells were preincubated with dihydrolipoic acid ( 0.2 mM ) the expression of c-fos mRNA was suppressed at 30 min after stimulation of TPA ( 0.5 microM ) whereas in the case of preincubation of alpha-lipoic acid ( 0.2 microM ) , the expression was enhanced at 30 min .", "annotated_text": "When cells were preincubated with dihydrolipoic acid ( 0.2 mM ) the expression of <rna>c-fos mRNA</rna> was suppressed at 30 min after stimulation of TPA ( 0.5 microM ) whereas in the case of preincubation of alpha-lipoic acid ( 0.2 microM ) , the expression was enhanced at 30 min ."}143{"id": "142", "text": "These studies support the idea that superoxide anion radical plays a role in the expression of c-fos mRNA .", "annotated_text": "These studies support the idea that superoxide anion radical plays a role in the expression of <rna>c-fos mRNA</rna> ."}144{"id": "143", "text": "Appraisal of potential therapeutic index of antioxidants on the basis of their in vitro effects on HIV replication in monocytes and interleukin 2 -induced lymphocyte proliferation .", "annotated_text": "Appraisal of potential therapeutic index of antioxidants on the basis of their in vitro effects on HIV replication in <cell_type>monocytes</cell_type> and <protein>interleukin 2</protein> -induced lymphocyte proliferation ."}145{"id": "144", "text": "Antioxidant molecules have been suggested to be of therapeutic value in the treatment of HIV-infected patients .", "annotated_text": "Antioxidant molecules have been suggested to be of therapeutic value in the treatment of HIV-infected patients ."}146{"id": "145", "text": "To evaluate this possibility , we examined in vitro the effects of two types of antioxidant molecules in terms of inhibition of HIV replication in monocytes , one of the main reservoirs of HIV , and also in terms of modulation of the immune competence as measured by PBMC proliferation .", "annotated_text": "To evaluate this possibility , we examined in vitro the effects of two types of antioxidant molecules in terms of inhibition of HIV replication in <cell_type>monocytes</cell_type> , one of the main reservoirs of HIV , and also in terms of modulation of the immune competence as measured by <cell_type>PBMC</cell_type> proliferation ."}147{"id": "146", "text": "We tested the effects of BHA , a phenolic , lipid-soluble , chain-breaking antioxidant , and NAC , a known glutathione precursor with some direct free-radical scavenging properties as well , on the regulation of HIV-1 expression in latently infected U1 cells and in productively and chronically infected U937 cells .", "annotated_text": "We tested the effects of BHA , a phenolic , lipid-soluble , chain-breaking antioxidant , and NAC , a known glutathione precursor with some direct free-radical scavenging properties as well , on the regulation of HIV-1 expression in latently infected <cell_line>U1 cells</cell_line> and in productively and chronically infected <cell_line>U937 cells</cell_line> ."}148{"id": "147", "text": "Both antioxidants inhibited TNF -or PMA-induced NF-kappa B activity in U1 cells , as well as the sustained NF-kappa B activity permanently induced by the virus itself in chronically HIV-infected U937 cells .", "annotated_text": "Both antioxidants inhibited <protein>TNF</protein> -or PMA-induced <protein>NF-kappa B</protein> activity in <cell_line>U1 cells</cell_line> , as well as the sustained <protein>NF-kappa B</protein> activity permanently induced by the virus itself in chronically HIV-infected <cell_line>U937 cells</cell_line> ."}149{"id": "148", "text": "This resulted in only a partial inhibition of TNF -or PMA- induced HIV replication in U1 cells , and no detectable effect on HIV replication in chronically infected U937 cells .", "annotated_text": "This resulted in only a partial inhibition of <protein>TNF</protein> -or PMA- induced HIV replication in <cell_line>U1 cells</cell_line> , and no detectable effect on HIV replication in <cell_line>chronically infected U937 cells</cell_line> ."}150{"id": "149", "text": "This may be the first limitation to potential antiviral effects of antioxidant therapies .", "annotated_text": "This may be the first limitation to potential antiviral effects of antioxidant therapies ."}151{"id": "150", "text": "Another limitation is that antioxidant concentrations high enough to block NK-kappa B activation were shown to have a suppressive effect on immune functions in vitro , because NAC and BHA blocked IL-2-induced PBMC proliferation .", "annotated_text": "Another limitation is that antioxidant concentrations high enough to block <protein>NK-kappa B</protein> activation were shown to have a suppressive effect on immune functions in vitro , because NAC and BHA blocked <cell_type>IL-2-induced PBMC</cell_type> proliferation ."}152{"id": "151", "text": "These data warrant prudence in the design of antioxidant-based therapies aimed at suppressing HIV replication .", "annotated_text": "These data warrant prudence in the design of antioxidant-based therapies aimed at suppressing HIV replication ."}153{"id": "152", "text": "Isolation and characterization of gelatinase granules from human neutrophils .", "annotated_text": "Isolation and characterization of gelatinase granules from <cell_type>human neutrophils</cell_type> ."}154{"id": "153", "text": "We recently confirmed the existence of gelatinase granules as a subpopulation of peroxidase-negative granules by double-labeling immunogold electron microscopy on intact cells and by subcellular fractionation .", "annotated_text": "We recently confirmed the existence of gelatinase granules as a subpopulation of peroxidase-negative granules by double-labeling immunogold electron microscopy on intact cells and by subcellular fractionation ."}155{"id": "154", "text": "Further characterization of gelatinase granules has been hampered by poor separation of specific and gelatinase granules on both two-layer Percoll gradients and sucrose gradients .", "annotated_text": "Further characterization of gelatinase granules has been hampered by poor separation of specific and gelatinase granules on both two-layer Percoll gradients and sucrose gradients ."}156{"id": "155", "text": "We have developed a three-layer Percoll density gradient that allows separation of the different granules and vesicles from human neutrophils ; in particular , it allows separation of specific and gelatinase granules .", "annotated_text": "We have developed a three-layer Percoll density gradient that allows separation of the different granules and vesicles from <cell_type>human neutrophils</cell_type> ; in particular , it allows separation of specific and gelatinase granules ."}157{"id": "156", "text": "This allows us to characterize these two granule populations with regard to their content of membrane proteins , which become incorporated into the plasma membrane during exocytosis .", "annotated_text": "This allows us to characterize these two granule populations with regard to their content of <protein>membrane proteins</protein> , which become incorporated into the plasma membrane during exocytosis ."}158{"id": "157", "text": "We found that gelatinase granules , defined as peroxidase-negative granules containing gelatinase but lacking lactoferrin , contain 50 % of total cell gelatinase , with the remaining residing in specific granules .", "annotated_text": "We found that gelatinase granules , defined as peroxidase-negative granules containing <protein>gelatinase</protein> but lacking <protein>lactoferrin</protein> , contain 50 % of total cell <protein>gelatinase</protein> , with the remaining residing in specific granules ."}159{"id": "158", "text": "Furthermore , we found that 20 % to 25 % of both the adhesion protein Mac-1 and the NADPH-oxidase component cytochrome b558 is localized in gelatinase granules .", "annotated_text": "Furthermore , we found that 20 % to 25 % of both the <protein>adhesion protein Mac-1</protein> and the <protein>NADPH-oxidase component cytochrome</protein> <protein>b558</protein> is localized in <protein>gelatinase</protein> granules ."}160{"id": "159", "text": "Although no qualitative difference was observed between specific granules and gelatinase granules with respect to cytochrome b558 and Mac-1 , stimulation of the neutrophil with FMLP resulted in a selective mobilization of the least dense peroxidase-negative granules , ie , gelatinase granules , which , in concert with secretory vesicles , furnish the plasma membrane with Mac-1 and cytochrome b558 .", "annotated_text": "Although no qualitative difference was observed between specific granules and <protein>gelatinase</protein> granules with respect to <protein>cytochrome b558</protein> and <protein>Mac-1</protein> , stimulation of the <cell_type>neutrophil</cell_type> with <protein>FMLP</protein> resulted in a selective mobilization of the least dense peroxidase-negative granules , ie , <protein>gelatinase</protein> granules , which , in concert with secretory vesicles , furnish the plasma membrane with <protein>Mac-1</protein> and <protein>cytochrome b558</protein> ."}161{"id": "160", "text": "This shows that gelatinase granules are functionally important relative to specific granules in mediating early inflammatory responses .", "annotated_text": "This shows that <protein>gelatinase</protein> granules are functionally important relative to specific granules in mediating early inflammatory responses ."}162{"id": "161", "text": "Regulation of interleukin-2 receptor alpha chain expression and nuclear factor.kappa B activation by protein kinase C in T lymphocytes .", "annotated_text": "Regulation of <protein>interleukin-2 receptor alpha chain</protein> expression and <protein>nuclear factor.kappa B</protein> activation by <protein>protein kinase C</protein> in <cell_type>T lymphocytes</cell_type> ."}163{"id": "162", "text": "Autocrine role of tumor necrosis factor alpha .", "annotated_text": "Autocrine role of <protein>tumor necrosis factor alpha</protein> ."}164{"id": "163", "text": "The regulation of interleukin-2 receptor alpha chain ( IL-2R alpha ) expression and nuclear factor ( NF ) activation by protein kinase C ( PKC ) in resting T cells , has been studied .", "annotated_text": "The regulation of <protein>interleukin-2 receptor alpha chain</protein> ( <protein>IL-2R alpha</protein> ) expression and <protein>nuclear factor</protein> ( NF ) activation by <protein>protein kinase C</protein> ( <protein>PKC</protein> ) in <cell_type>resting T cells</cell_type> , has been studied ."}165{"id": "164", "text": "Treatment of human resting T cells with phorbol esters strongly induced the expression of IL-2R alpha and the activation of NF.kappa B .", "annotated_text": "Treatment of human <cell_type>resting T cells</cell_type> with phorbol esters strongly induced the expression of <protein>IL-2R alpha</protein> and the activation of <protein>NF.kappa B</protein> ."}166{"id": "165", "text": "This activation was due to the translocation of p65 and c-Rel NF.kappa B proteins from cytoplasmic stores to the nucleus , where they bound the kappa B sequence of the IL-2R alpha promoter either as p50.p65 or as p50.c-Rel heterodimers .", "annotated_text": "This activation was due to the translocation of <protein>p65</protein> and <protein>c-Rel</protein> <protein>NF.kappa B</protein> proteins from cytoplasmic stores to the nucleus , where they bound the <dna>kappa B sequence</dna> of the <dna>IL-2R alpha promoter</dna> either as <protein>p50.p65</protein> or as <protein>p50.c-Rel</protein> heterodimers ."}167{"id": "166", "text": "Interestingly , all of those events were largely indirect and mediated by endogenously secreted tumor necrosis factor alpha ( TNF alpha ) , as they were strongly inhibited by a neutralizing anti-TNF alpha monoclonal antibody .", "annotated_text": "Interestingly , all of those events were largely indirect and mediated by endogenously secreted <protein>tumor necrosis factor alpha</protein> ( <protein>TNF alpha</protein> ) , as they were strongly inhibited by a <protein>neutralizing anti-TNF alpha monoclonal antibody</protein> ."}168{"id": "167", "text": "Furthermore , cyclosporin A , which blocked TNF alpha production induced by PKC , strongly inhibited IL-2R alpha and NF.kappa B activation .", "annotated_text": "Furthermore , cyclosporin A , which blocked <protein>TNF alpha</protein> production induced by <protein>PKC</protein> , strongly inhibited <protein>IL-2R alpha</protein> and <protein>NF.kappa B</protein> activation ."}169{"id": "168", "text": "The addition of either TNF alpha or IL-2 partially recovered cyclosporin A-induced IL-2R alpha inhibition , but only TNF alpha completely recovered NF.kappa B activation .", "annotated_text": "The addition of either <protein>TNF alpha</protein> or <protein>IL-2</protein> partially recovered cyclosporin A-induced <protein>IL-2R alpha</protein> inhibition , but only <protein>TNF alpha</protein> completely recovered <protein>NF.kappa B</protein> activation ."}170{"id": "169", "text": "Those results indicate that , in resting T cells , PKC activation has only a triggering role , whereas the endogenously secreted TNF alpha plays an essential role in the quantitative control of the expression of IL-2R alpha chain or NF.kappa B activation .", "annotated_text": "Those results indicate that , in <cell_type>resting T cells</cell_type> , <protein>PKC</protein> activation has only a triggering role , whereas the endogenously secreted <protein>TNF alpha</protein> plays an essential role in the quantitative control of the expression of <protein>IL-2R alpha</protein> chain or <protein>NF.kappa B</protein> activation ."}171{"id": "170", "text": "Superantigens activate HIV-1 gene expression in monocytic cells .", "annotated_text": "<protein>Superantigens</protein> activate HIV-1 gene expression in <cell_type>monocytic cells</cell_type> ."}172{"id": "171", "text": "Binding of superantigens to MHC class II molecules results in transduction of biochemical signals leading to cellular activation and gene expression .", "annotated_text": "Binding of superantigens to <protein>MHC class II molecules</protein> results in transduction of biochemical signals leading to cellular activation and gene expression ."}173{"id": "172", "text": "We demonstrate that the staphylococcal superantigens toxic shock syndrome toxin-1 ( TSST-1 ) and staphylococcal enterotoxin A ( SEA ) activate HIV-1-LTR -driven transcription of chloramphenicol acetyl transferase in the human monocytic cell line THP-1 .", "annotated_text": "We demonstrate that the <protein>staphylococcal superantigens</protein> <protein>toxic shock syndrome toxin-1</protein> ( <protein>TSST-1</protein> ) and <protein>staphylococcal enterotoxin A</protein> ( <protein>SEA</protein> ) activate <dna>HIV-1-LTR</dna> -driven transcription of <protein>chloramphenicol acetyl transferase</protein> in the <cell_line>human monocytic cell line</cell_line> <cell_line>THP-1</cell_line> ."}174{"id": "173", "text": "Induction of HIV-1- LTR -driven transcription in THP-1 cells by superantigens was associated with the induction of nuclear factor-kappa B DNA-binding activity .", "annotated_text": "Induction of HIV-1- <dna>LTR</dna> -driven transcription in <cell_line>THP-1 cells</cell_line> by <protein>superantigens</protein> was associated with the induction of <protein>nuclear factor-kappa B</protein> DNA-binding activity ."}175{"id": "174", "text": "Superantigens also increased viral protein secretion from the granulocyte-macrophage colony-stimulating factor-pretreated chronically infected human monocytic cell line U1 .", "annotated_text": "<protein>Superantigens</protein> also increased viral protein secretion from the <cell_line>granulocyte-macrophage colony-stimulating factor-pretreated chronically infected human monocytic cell line U1</cell_line> ."}176{"id": "175", "text": "Induction of HIV-1 gene expression in monocytic cells by superantigens occurred via tumor necrosis factor-alpha-dependent and -independent mechanisms .", "annotated_text": "Induction of HIV-1 gene expression in <cell_type>monocytic cells</cell_type> by <protein>superantigens</protein> occurred via tumor necrosis factor-alpha-dependent and -independent mechanisms ."}177{"id": "176", "text": "Our results suggest that superantigens and other MHC class II ligands may activate HIV-1 gene expression in monocytes/macrophages .", "annotated_text": "Our results suggest that <protein>superantigens</protein> and other <protein>MHC class II ligands</protein> may activate HIV-1 gene expression in <cell_type>monocytes/macrophages</cell_type> ."}178{"id": "177", "text": "Mitogen activation of human peripheral T lymphocytes induces the formation of new cyclic AMP response element-binding protein nuclear complexes .", "annotated_text": "Mitogen activation of <cell_type>human peripheral T lymphocytes</cell_type> induces the formation of new <protein>cyclic AMP response element-binding protein nuclear complexes</protein> ."}179{"id": "178", "text": "A large body of evidence indicates that experimental agents which raise cellular cAMP levels inhibit T cell growth and division .", "annotated_text": "A large body of evidence indicates that experimental agents which raise cellular cAMP levels inhibit T cell growth and division ."}180{"id": "179", "text": "By contrast , many studies have reported that mitogen activation of T cells increases cAMP levels , implying a positive physiological role for cAMP in the activation process .", "annotated_text": "By contrast , many studies have reported that <protein>mitogen</protein> activation of <cell_type>T cells</cell_type> increases cAMP levels , implying a positive physiological role for cAMP in the activation process ."}181{"id": "180", "text": "In the present study we demonstrate that mitogen activation of human peripheral T lymphocytes induces nuclear factors that form complexes with cyclic AMP response element-binding protein ( CREB ) .", "annotated_text": "In the present study we demonstrate that <protein>mitogen</protein> activation of <cell_type>human peripheral T lymphocytes</cell_type> induces nuclear factors that form complexes with <protein>cyclic AMP response element-binding protein</protein> ( <protein>CREB</protein> ) ."}182{"id": "181", "text": "Four complexes are identified by the electrophoretic mobility shift assay , two of which are induced by mitogen activation .", "annotated_text": "Four complexes are identified by the electrophoretic mobility shift assay , two of which are induced by <protein>mitogen</protein> activation ."}183{"id": "182", "text": "All four complexes contain CREB and are bound to the cAMP response element ( CRE ) core sequence ( TGACGTCA ) , as indicated by antibody and oligonucleotide competition experiments .", "annotated_text": "All four complexes contain <protein>CREB</protein> and are bound to the <dna>cAMP response element ( CRE ) core sequence</dna> ( TGACGTCA ) , as indicated by antibody and oligonucleotide competition experiments ."}184{"id": "183", "text": "Binding of the four complexes to CRE is prevented by dephosphorylation of nuclear extracts and is restored by rephosphorylation with cAMP-dependent protein kinase or endogenous kinases .", "annotated_text": "Binding of the four complexes to <dna>CRE</dna> is prevented by dephosphorylation of nuclear extracts and is restored by rephosphorylation with <protein>cAMP-dependent protein kinase</protein> or <protein>endogenous kinases</protein> ."}185{"id": "184", "text": "Similar complexes are detected in nuclear extracts of Jurkat cells .", "annotated_text": "Similar complexes are detected in nuclear extracts of <cell_line>Jurkat cells</cell_line> ."}186{"id": "185", "text": "Mitogen induction of the electrophoretic mobility shift assay complexes is not accounted for by protein phosphorylation or by induction of CREB .", "annotated_text": "Mitogen induction of the <protein>electrophoretic mobility shift assay complexes</protein> is not accounted for by protein phosphorylation or by induction of <protein>CREB</protein> ."}187{"id": "186", "text": "Rather , the data indicate that mitogen increases the levels of a nuclear factor ( s ) that dimerizes with CREB .", "annotated_text": "Rather , the data indicate that mitogen increases the levels of a nuclear factor ( s ) that dimerizes with <protein>CREB</protein> ."}188{"id": "187", "text": "Induction of new CREB complexes implies a physiological role for cAMP in mitogen activation of T lymphocytes .", "annotated_text": "Induction of new <protein>CREB complexes</protein> implies a physiological role for cAMP in <protein>mitogen</protein> activation of <cell_type>T lymphocytes</cell_type> ."}189{"id": "188", "text": "Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells .", "annotated_text": "Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to <cell_line>cultured human endothelial cells</cell_line> ."}190{"id": "189", "text": "Antioxidants have been proposed to be anti-atherosclerotic agents ; however , the mechanisms underlying their beneficial effects are poorly understood .", "annotated_text": "Antioxidants have been proposed to be anti-atherosclerotic agents ; however , the mechanisms underlying their beneficial effects are poorly understood ."}191{"id": "190", "text": "We have examined the effect of alpha-tocopherol ( alpha-tcp ) on one cellular event in atherosclerotic plaque development , monocyte adhesion to stimulated endothelial cells ( ECs ) .", "annotated_text": "We have examined the effect of alpha-tocopherol ( alpha-tcp ) on one cellular event in atherosclerotic plaque development , monocyte adhesion to <cell_type>stimulated endothelial cells</cell_type> ( <cell_type>ECs</cell_type> ) ."}192{"id": "191", "text": "Human umbilical vein ECs were pretreated with alpha-tcp before stimulation with known agonists of monocyte adhesion : IL-1 ( 10 ng/ml ) , LPS ( 10 ng/ml ) , thrombin ( 30 U/ml ) , or PMA ( 10 nM ) .", "annotated_text": "Human umbilical vein <cell_type>ECs</cell_type> were pretreated with alpha-tcp before stimulation with known agonists of monocyte adhesion : <protein>IL-1</protein> ( 10 ng/ml ) , LPS ( 10 ng/ml ) , <protein>thrombin</protein> ( 30 U/ml ) , or PMA ( 10 nM ) ."}193{"id": "192", "text": "Agonist-induced monocytic cell adhesion , but not basal adhesion , was inhibited in a time- and concentration-dependent manner by alpha-tcp .", "annotated_text": "Agonist-induced monocytic cell adhesion , but not basal adhesion , was inhibited in a time- and concentration-dependent manner by alpha-tcp ."}194{"id": "193", "text": "The IC50 of alpha-tcp on an IL-1 -induced response was 45 microM .", "annotated_text": "The IC50 of alpha-tcp on an <protein>IL-1</protein> -induced response was 45 microM ."}195{"id": "194", "text": "The inhibition correlated with a decrease in steady state levels of E-selectin mRNA and cell surface expression of E-selectin which is consistent with the ability of a monoclonal antibody to E-selectin to inhibit monocytic cell adhesion in this system .", "annotated_text": "The inhibition correlated with a decrease in steady state levels of <rna>E-selectin mRNA</rna> and cell surface expression of <protein>E-selectin</protein> which is consistent with the ability of a <protein>monoclonal antibody</protein> to <protein>E-selectin</protein> to inhibit monocytic cell adhesion in this system ."}196{"id": "195", "text": "Probucol ( 50 microM ) and N-acetylcysteine ( 20 mM ) also inhibited agonist-induced monocytic cell adhesion ; whereas , several other antioxidants had no significant effect .", "annotated_text": "Probucol ( 50 microM ) and N-acetylcysteine ( 20 mM ) also inhibited agonist-induced monocytic cell adhesion ; whereas , several other antioxidants had no significant effect ."}197{"id": "196", "text": "Protein kinase C ( PKC ) does not appear to play a role in the alpha-tcp effect since no suppression of phosphorylation of PKC substrates was observed .", "annotated_text": "<protein>Protein kinase C</protein> ( <protein>PKC</protein> ) does not appear to play a role in the alpha-tcp effect since no suppression of phosphorylation of <protein>PKC</protein> substrates was observed ."}198{"id": "197", "text": "Activation of the transcription factor NF-kappa B is reported to be necessary but not sufficient for E-selectin expression in EC .", "annotated_text": "Activation of the <protein>transcription factor</protein> <protein>NF-kappa B</protein> is reported to be necessary but not sufficient for <protein>E-selectin</protein> expression in <cell_line>EC</cell_line> ."}199{"id": "198", "text": "Electrophoretic mobility shift assays failed to show an alpha-tcp-induced decrease in activation of this transcription factor after cytokine stimulation .", "annotated_text": "Electrophoretic mobility shift assays failed to show an alpha-tcp-induced decrease in activation of this <protein>transcription factor</protein> after <protein>cytokine</protein> stimulation ."}200{"id": "199", "text": "It has been hypothesized that alpha-tcp acts as an anti-atherosclerotic molecule by inhibiting generation of oxidized LDL -- a putative triggering molecule in the atherosclerotic process .", "annotated_text": "It has been hypothesized that alpha-tcp acts as an anti-atherosclerotic molecule by inhibiting generation of oxidized LDL -- a putative triggering molecule in the atherosclerotic process ."}201{"id": "200", "text": "Our results point to a novel alternative mechanism of action of alpha-tcp .", "annotated_text": "Our results point to a novel alternative mechanism of action of alpha-tcp ."}202{"id": "201", "text": "Central nervous system-derived cells express a kappa B-binding activity that enhances human immunodeficiency virus type 1 transcription in vitro and facilitates TAR -independent transactivation by Tat .", "annotated_text": "<cell_type>Central nervous system-derived cells</cell_type> express a kappa B-binding activity that enhances human immunodeficiency virus type 1 transcription in vitro and facilitates <dna>TAR</dna> -independent transactivation by <protein>Tat</protein> ."}203{"id": "202", "text": "The Tat protein of human immunodeficiency virus type 1 ( HIV-1 ) is a potent activator of long terminal repeat -directed transcription .", "annotated_text": "The <protein>Tat protein</protein> of human immunodeficiency virus type 1 ( HIV-1 ) is a potent activator of <dna>long terminal repeat</dna> -directed transcription ."}204{"id": "203", "text": "While in most cell types , activation requires interaction of Tat with the unusual transcription element TAR , astrocytic glial cells support TAR -independent transactivation of HIV-1 transcription by Tat .", "annotated_text": "While in most cell types , activation requires interaction of Tat with the unusual <dna>transcription element</dna> <dna>TAR</dna> , <cell_type>astrocytic glial cells</cell_type> support <dna>TAR</dna> -independent transactivation of HIV-1 transcription by Tat ."}205{"id": "204", "text": "This alternative pathway of Tat activation is mediated by the viral enhancer , a kappa B domain capable of binding the prototypical form of the transcription factor nuclear factor kappa B ( NF-kappa B ) present in many cell types , including T lymphocytes .", "annotated_text": "This alternative pathway of <protein>Tat</protein> activation is mediated by the <dna>viral enhancer</dna> , a kappa B domain capable of binding the prototypical form of the <protein>transcription factor</protein> nuclear factor kappa B ( <protein>NF-kappa B</protein> ) present in many cell types , including <cell_type>T lymphocytes</cell_type> ."}206{"id": "205", "text": "Tat transactivation mediated by the kappa B domain is sufficient to allow replication of TAR -deleted mutant HIV-1 in astrocytes .", "annotated_text": "<protein>Tat</protein> transactivation mediated by the <dna>kappa B domain</dna> is sufficient to allow replication of <dna>TAR</dna> -deleted mutant HIV-1 in <cell_type>astrocytes</cell_type> ."}207{"id": "206", "text": "The present study demonstrates the existence of kappa B-specific binding factors present in human glial astrocytes that differ from prototypical NF-kappa B .", "annotated_text": "The present study demonstrates the existence of <protein>kappa B-specific binding factors</protein> present in <cell_type>human glial astrocytes</cell_type> that differ from prototypical <protein>NF-kappa B</protein> ."}208{"id": "207", "text": "The novel astrocyte-derived kappa B-binding activity is retained on an HIV-1 Tat affinity column , while prototypical NF-kappa B from Jurkat T cells is not .", "annotated_text": "The novel astrocyte-derived kappa B-binding activity is retained on an HIV-1 <protein>Tat</protein> affinity column , while prototypical <protein>NF-kappa B</protein> from <cell_line>Jurkat T cells</cell_line> is not ."}209{"id": "208", "text": "In vitro transcription studies demonstrate that astrocyte-derived kappa B-binding factors activate transcription of the HIV-1 long terminal repeat and that this activation is dependent on the kappa B domain .", "annotated_text": "In vitro transcription studies demonstrate that <protein>astrocyte-derived kappa B-binding factors</protein> activate transcription of the <dna>HIV-1 long terminal repeat</dna> and that this activation is dependent on the <dna>kappa B domain</dna> ."}210{"id": "209", "text": "Moreover , TAR -independent transactivation of HIV-1 transcription is reproduced in vitro in an astrocyte factor-dependent manner which correlates with kappa B-binding activity .", "annotated_text": "Moreover , <dna>TAR</dna> -independent transactivation of HIV-1 transcription is reproduced in vitro in an astrocyte factor-dependent manner which correlates with kappa B-binding activity ."}211{"id": "210", "text": "The importance of the central nervous system-enriched kappa B transcription factor in the regulation of HIV-1 expression is discussed .", "annotated_text": "The importance of the <protein>central nervous system-enriched kappa B</protein> <protein>transcription factor</protein> in the regulation of HIV-1 expression is discussed ."}212{"id": "211", "text": "Human interleukin-13 activates the interleukin-4-dependent transcription factor NF-IL4 sharing a DNA binding motif with an interferon-gamma-induced nuclear binding factor .", "annotated_text": "<protein>Human interleukin-13</protein> activates the <protein>interleukin-4-dependent transcription factor</protein> <protein>NF-IL4</protein> sharing a <protein>DNA binding motif</protein> with an <protein>interferon-gamma-induced nuclear binding factor</protein> ."}213{"id": "212", "text": "The effects of interleukin-13 ( IL-13 ) and interleukin-4 ( IL-4 ) on cellular functions were shown to be quite similar .", "annotated_text": "The effects of <protein>interleukin-13</protein> ( <protein>IL-13</protein> ) and <protein>interleukin-4</protein> ( <protein>IL-4</protein> ) on cellular functions were shown to be quite similar ."}214{"id": "213", "text": "We provide evidence that in monocytes as well as in T lymphocytes both IL-4 and IL-13 activate the same recently identified transcription factor NF-IL4 which binds to the specific responsive element IL-4RE .", "annotated_text": "We provide evidence that in monocytes as well as in <cell_type>T lymphocytes</cell_type> both <protein>IL-4</protein> and <protein>IL-13</protein> activate the same recently identified <protein>transcription factor</protein> <protein>NF-IL4</protein> which binds to the <dna>specific responsive element IL-4RE</dna> ."}215{"id": "214", "text": "In addition , we show that a nuclear factor activated by interferon-gamma also interacts with the IL-4RE .", "annotated_text": "In addition , we show that a <protein>nuclear factor</protein> activated by interferon-gamma also interacts with the <dna>IL-4RE</dna> ."}216{"id": "215", "text": "It differs from NF-IL4 in the electrophoretic mobility of the complex with DNA , in its DNA-binding specificity and in the proteins interacting with the DNA sequence .", "annotated_text": "It differs from <protein>NF-IL4</protein> in the electrophoretic mobility of the complex with DNA , in its DNA-binding specificity and in the proteins interacting with the <dna>DNA sequence</dna> ."}217{"id": "216", "text": "Sensitivity against various enzyme inhibitors suggests that components of the signal transduction pathway are shared by all three cytokines .", "annotated_text": "Sensitivity against various enzyme inhibitors suggests that components of the signal transduction pathway are shared by all three <protein>cytokines</protein> ."}218{"id": "217", "text": "Encephalomyocarditis virus internal ribosomal entry site RNA-protein interactions .", "annotated_text": "Encephalomyocarditis virus internal ribosomal entry site RNA-protein interactions ."}219{"id": "218", "text": "Translational initiation of encephalomyocarditis virus ( EMCV ) mRNA occurs by ribosomal entry into the 5 ' nontranslated region of the EMCV mRNA , rather than by ribosomal scanning .", "annotated_text": "Translational initiation of <rna>encephalomyocarditis virus ( EMCV ) mRNA</rna> occurs by ribosomal entry into the <dna>5 ' nontranslated region</dna> of the <rna>EMCV mRNA</rna> , rather than by ribosomal scanning ."}220{"id": "219", "text": "Internal ribosomal binding requires a cis-acting element termed the internal ribosomal entry site ( IRES ) .", "annotated_text": "Internal ribosomal binding requires a <dna>cis-acting element</dna> termed the <dna>internal ribosomal entry site</dna> ( <dna>IRES</dna> ) ."}221{"id": "220", "text": "IRES elements have been proposed to be involved in the translation of picornavirus mRNAs and some cellular mRNAs .", "annotated_text": "<dna>IRES elements</dna> have been proposed to be involved in the translation of <rna>picornavirus mRNAs</rna> and some <rna>cellular mRNAs</rna> ."}222{"id": "221", "text": "Internal ribosome binding likely requires the interaction of trans-acting factors that recognize both the mRNA and the ribosomal complex .", "annotated_text": "Internal ribosome binding likely requires the interaction of <protein>trans-acting factors</protein> that recognize both the <rna>mRNA</rna> and the <protein>ribosomal complex</protein> ."}223{"id": "222", "text": "Five cellular proteins ( p52 , p57 , p70 , p72 , and p100 ) cross-link the EMCV IRES or fragments of the IRES .", "annotated_text": "Five <protein>cellular proteins</protein> ( <protein>p52</protein> , <protein>p57</protein> , <protein>p70</protein> , <protein>p72</protein> , and <protein>p100</protein> ) cross-link the EMCV <dna>IRES</dna> or fragments of the <dna>IRES</dna> ."}224{"id": "223", "text": "For one of these proteins , p57 , binding to the IRES correlates with translation .", "annotated_text": "For one of these proteins , <protein>p57</protein> , binding to the <dna>IRES</dna> correlates with translation ."}225{"id": "224", "text": "Recently , p57 was identified to be very similar , if not identical , to polypyrimidine tract-binding protein .", "annotated_text": "Recently , <protein>p57</protein> was identified to be very similar , if not identical , to <protein>polypyrimidine tract-binding protein</protein> ."}226{"id": "225", "text": "On the basis of cross-linking results with 21 different EMCV IRES fragments and cytoplasmic HeLa extract or rabbit reticulocyte lysate as the source of polypeptides , consensus binding sites for p52 , p57 , p70 , and p100 are proposed .", "annotated_text": "On the basis of cross-linking results with 21 different <dna>EMCV IRES fragments</dna> and cytoplasmic HeLa extract or rabbit reticulocyte lysate as the source of polypeptides , <dna>consensus binding sites</dna> for <protein>p52</protein> , <protein>p57</protein> , <protein>p70</protein> , and <protein>p100</protein> are proposed ."}227{"id": "226", "text": "It is suggested that each of these proteins recognizes primarily a structural feature of the RNA rather than a specific sequence .", "annotated_text": "It is suggested that each of these proteins recognizes primarily a structural feature of the RNA rather than a specific sequence ."}228{"id": "227", "text": "A novel heterodimerization partner for thyroid hormone receptor .", "annotated_text": "A novel <protein>heterodimerization partner</protein> for <protein>thyroid hormone receptor</protein> ."}229{"id": "228", "text": "Peroxisome proliferator-activated receptor .", "annotated_text": "<protein>Peroxisome proliferator-activated receptor</protein> ."}230{"id": "229", "text": "Retinoid-like receptors play a central role in hormonal responses by forming heterodimers with other nuclear hormone receptors .", "annotated_text": "<protein>Retinoid-like receptors</protein> play a central role in hormonal responses by forming <protein>heterodimers</protein> with other <protein>nuclear hormone receptors</protein> ."}231{"id": "230", "text": "In this study we have identified the peroxisome proliferator-activated receptor ( PPAR ) as a new thyroid hormone receptor ( THR ) auxiliary nuclear protein , heterodimerizing with THR in solution .", "annotated_text": "In this study we have identified the <protein>peroxisome proliferator-activated receptor</protein> ( <protein>PPAR</protein> ) as a new <protein>thyroid hormone receptor ( THR ) auxiliary nuclear protein</protein> , heterodimerizing with <protein>THR</protein> in solution ."}232{"id": "231", "text": "Although these heterodimers do not recognize a classical thyroid hormone response element ( TRE ) characterized by direct repeat separated by four nucleotides ( DR+4 ) , PPAR behaves as a dominant negative regulator of thyroid hormone ( TH ) action .", "annotated_text": "Although these <protein>heterodimers</protein> do not recognize a classical <dna>thyroid hormone response element</dna> ( <dna>TRE</dna> ) characterized by direct repeat separated by four nucleotides ( <dna>DR+4</dna> ) , <protein>PPAR</protein> behaves as a dominant negative regulator of thyroid hormone ( TH ) action ."}233{"id": "232", "text": "However , a TH-dependent positive effect is elicited by selective interaction of the THR beta-PPAR but not the THR alpha-PPAR heterodimer with a novel TRE ( DR+2 ) .", "annotated_text": "However , a TH-dependent positive effect is elicited by selective interaction of the <protein>THR beta-PPAR</protein> but not the <protein>THR alpha-PPAR heterodimer</protein> with a novel <dna>TRE</dna> ( <dna>DR+2</dna> ) ."}234{"id": "233", "text": "The critical region of THR beta was mapped to 3 amino acids in the distal box of the DNA binding domain .", "annotated_text": "The critical region of <protein>THR</protein> beta was mapped to 3 amino acids in the <protein>distal box</protein> of the <protein>DNA binding domain</protein> ."}235{"id": "234", "text": "Hence , PPAR can positively or negatively influence TH action depending on TRE structure and THR isotype .", "annotated_text": "Hence , <protein>PPAR</protein> can positively or negatively influence TH action depending on <dna>TRE</dna> structure and <protein>THR isotype</protein> ."}236{"id": "235", "text": "Comparison of retinoic acid and phorbol myristate acetate as inducers of monocytic differentiation .", "annotated_text": "Comparison of retinoic acid and phorbol myristate acetate as inducers of monocytic differentiation ."}237{"id": "236", "text": "Several human myeloid leukemia cell lines growing in vitro can be induced to differentiate to more mature monocyte/macrophage-like cells by treatment with protein kinase C -activating phorbol esters , such as PMA .", "annotated_text": "Several <cell_line>human myeloid leukemia cell lines</cell_line> growing in vitro can be induced to differentiate to more mature <cell_type>monocyte/macrophage-like cells</cell_type> by treatment with <protein>protein kinase C</protein> -activating phorbol esters , such as PMA ."}238{"id": "237", "text": "In addition to PMA , cells of the THP-1 myeloid leukemia cell line acquire macrophage-like characteristics after treatment with all-trans retinoic acid ( RA ) .", "annotated_text": "In addition to PMA , cells of the <cell_line>THP-1 myeloid leukemia cell line</cell_line> acquire macrophage-like characteristics after treatment with all-trans retinoic acid ( RA ) ."}239{"id": "238", "text": "To analyze the signal transduction mechanisms induced by RA , we first compared the effects of PMA and RA on the expression of genes which are known to be regulated during monocytic differentiation .", "annotated_text": "To analyze the signal transduction mechanisms induced by RA , we first compared the effects of PMA and RA on the expression of genes which are known to be regulated during monocytic differentiation ."}240{"id": "239", "text": "Both RA and PMA effectively down-regulated c-myc expression , while c-myb expression decreased only after PMA treatment .", "annotated_text": "Both RA and PMA effectively down-regulated <dna>c-myc</dna> expression , while <dna>c-myb</dna> expression decreased only after PMA treatment ."}241{"id": "240", "text": "Expression of the beta 2-integrin genes , CD11a and CD11b , was clearly increased after both of these treatments .", "annotated_text": "Expression of the <dna>beta 2-integrin genes</dna> , <dna>CD11a</dna> and <dna>CD11b</dna> , was clearly increased after both of these treatments ."}242{"id": "241", "text": "Their effects on the src-family tyrosine kinase genes were different : hck expression was similarly induced by these agents but lyn expression was stronger and more rapid after RA treatment .", "annotated_text": "Their effects on the <dna>src-family tyrosine kinase genes</dna> were different : <dna>hck</dna> expression was similarly induced by these agents but lyn expression was stronger and more rapid after RA treatment ."}243{"id": "242", "text": "RA also enhanced lyn mRNA production rapidly in HL-60 , indicating that the activation of lyn gene expression is common in monocytic and granulocytic maturation of myeloid leukemia cells .", "annotated_text": "RA also enhanced <rna>lyn mRNA</rna> production rapidly in <cell_line>HL-60</cell_line> , indicating that the activation of <dna>lyn gene</dna> expression is common in monocytic and granulocytic maturation of <cell_type>myeloid leukemia cells</cell_type> ."}244{"id": "243", "text": "To examine whether the AP-1 enhancer activity is involved in RA-induced monocytic differentiation , THP-1 cells were transiently transfected with a chloramphenicol acetyl transferase ( CAT ) -reporter gene containing 5 copies of the AP-1 binding sites .", "annotated_text": "To examine whether the <dna>AP-1 enhancer</dna> activity is involved in RA-induced monocytic differentiation , <cell_line>THP-1 cells</cell_line> were transiently transfected with a <dna>chloramphenicol acetyl transferase ( CAT ) -reporter gene</dna> containing 5 copies of the <dna>AP-1 binding sites</dna> ."}245{"id": "244", "text": "In contrast to PMA , RA did not induce any CAT activity in these cells , thus suggesting that the RA-induced changes in the expression of those genes described above were not dependent on the AP-1 enhancer activity .", "annotated_text": "In contrast to PMA , RA did not induce any <protein>CAT</protein> activity in these cells , thus suggesting that the RA-induced changes in the expression of those genes described above were not dependent on the <dna>AP-1 enhancer</dna> activity ."}246{"id": "245", "text": "An active v-abl protein tyrosine kinase blocks immunoglobulin light-chain gene rearrangement .", "annotated_text": "An active <protein>v-abl protein tyrosine kinase</protein> blocks <dna>immunoglobulin light-chain gene</dna> rearrangement ."}247{"id": "246", "text": "Lymphoid cells transformed by Abelson murine leukemia virus have provided one of the classic models for study of early B-cell development and immunoglobulin rearrangement .", "annotated_text": "<cell_type>Lymphoid cells</cell_type> transformed by Abelson murine leukemia virus have provided one of the classic models for study of early B-cell development and <protein>immunoglobulin</protein> rearrangement ."}248{"id": "247", "text": "Most of these cells have rearranged their heavy-chain locus but not their light chain genes , suggesting that an active v-abl protein interferes with this differentiation step .", "annotated_text": "Most of these cells have rearranged their <dna>heavy-chain locus</dna> but not their <dna>light chain genes</dna> , suggesting that an active <protein>v-abl protein</protein> interferes with this differentiation step ."}249{"id": "248", "text": "To test this hypothesis , light-chain gene structure was examined in pre-B cells transformed by temperature-sensitive mutants of the Abelson virus and in derivatives that survive at the nonpermissive temperature because they express a human BCL-2 gene .", "annotated_text": "To test this hypothesis , <dna>light-chain gene structure</dna> was examined in <cell_line>pre-B cells</cell_line> transformed by temperature-sensitive mutants of the Abelson virus and in derivatives that survive at the nonpermissive temperature because they express a <dna>human BCL-2 gene</dna> ."}250{"id": "249", "text": "Our studies reveal that inactivation of the v-abl protein tyrosine kinase triggers high-frequency rearrangement of kappa and lambda light-chain genes .", "annotated_text": "Our studies reveal that inactivation of the <protein>v-abl protein tyrosine kinase</protein> triggers high-frequency rearrangement of <dna>kappa and lambda light-chain genes</dna> ."}251{"id": "250", "text": "These events are accompanied by marked increases in the expression of RAG-1 and RAG-2 RNAs .", "annotated_text": "These events are accompanied by marked increases in the expression of <rna>RAG-1 and RAG-2 RNAs</rna> ."}252{"id": "251", "text": "These increases occur in the absence of protein synthesis but are dependent on inactivation of the v-abl protein tyrosine kinase .", "annotated_text": "These increases occur in the absence of protein synthesis but are dependent on inactivation of the <protein>v-abl protein tyrosine kinase</protein> ."}253{"id": "252", "text": "As documented in the accompanying paper ( Klug et al. , this issue ) , an active v-abl protein also suppresses the activity of NF-kappa B/rel and expression controlled by the kappa intron enhancer .", "annotated_text": "As documented in the accompanying paper ( Klug et al. , this issue ) , an active <protein>v-abl protein</protein> also suppresses the activity of <protein>NF-kappa B/rel</protein> and expression controlled by the <dna>kappa intron enhancer</dna> ."}254{"id": "253", "text": "Together these data demonstrate that the v-abl protein specifically interferes with light-chain gene rearrangement by suppressing at least two pathways essential for this stage of B-cell differentiation and suggest that tyrosine phosphorylation is important in regulating RAG gene expression .", "annotated_text": "Together these data demonstrate that the <protein>v-abl protein</protein> specifically interferes with <dna>light-chain gene</dna> rearrangement by suppressing at least two pathways essential for this stage of <cell_type>B-cell</cell_type> differentiation and suggest that tyrosine phosphorylation is important in regulating <dna>RAG gene</dna> expression ."}255{"id": "254", "text": "Calcium signalling in T cells stimulated by a cyclophilin B-binding protein .", "annotated_text": "Calcium signalling in <cell_type>T cells</cell_type> stimulated by a <protein>cyclophilin B-binding protein</protein> ."}256{"id": "255", "text": "The immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from the T-cell receptor ( TCR ) that normally leads to T-cell activation .", "annotated_text": "The immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from the <protein>T-cell receptor</protein> ( <protein>TCR</protein> ) that normally leads to T-cell activation ."}257{"id": "256", "text": "When bound to cyclophilin , cyclosporin A binds and inactivates the key signalling intermediate calcineurin .", "annotated_text": "When bound to <protein>cyclophilin</protein> , cyclosporin A binds and inactivates the key signalling intermediate <protein>calcineurin</protein> ."}258{"id": "257", "text": "To identify potential cellular homologues of cyclosporin A that might regulate calcium signalling , we have cloned human genes encoding cyclophilin B-binding-proteins using the yeast two-hybrid system .", "annotated_text": "To identify potential cellular homologues of cyclosporin A that might regulate calcium signalling , we have cloned human genes encoding <protein>cyclophilin B-binding-proteins</protein> using the yeast two-hybrid system ."}259{"id": "258", "text": "One gene product , when overexpressed in Jurkat T cells , specifically induced transcription from the interleukin-2 enhancer , by activating the T-cell-specific transcription factors NF-AT and NF-IL2A .", "annotated_text": "One gene product , when overexpressed in <cell_line>Jurkat T cells</cell_line> , specifically induced transcription from the <dna>interleukin-2 enhancer</dna> , by activating the <protein>T-cell-specific transcription factors</protein> <protein>NF-AT</protein> and <protein>NF-IL2A</protein> ."}260{"id": "259", "text": "This protein , termed calcium-signal modulating cyclophilin ligand ( CAML ) , acts downstream of the TCR and upstream of calcineurin by causing an influx of calcium .", "annotated_text": "This protein , termed <protein>calcium-signal modulating cyclophilin ligand</protein> ( <protein>CAML</protein> ) , acts downstream of the <protein>TCR</protein> and upstream of <protein>calcineurin</protein> by causing an influx of calcium ."}261{"id": "260", "text": "CAML appears to be a new participant in the calcium-signal transduction pathway , implicating cyclophilin B in calcium signalling , even in the absence of cyclosporin .", "annotated_text": "<protein>CAML</protein> appears to be a new participant in the calcium-signal transduction pathway , implicating <protein>cyclophilin B</protein> in calcium signalling , even in the absence of cyclosporin ."}262{"id": "261", "text": "Expression and genomic configuration of GM-CSF , IL-3 , M-CSF receptor ( C-FMS ) , early growth response gene-1 ( EGR-1 ) and M-CSF genes in primary myelodysplastic syndromes .", "annotated_text": "Expression and genomic configuration of <protein>GM-CSF</protein> , <protein>IL-3</protein> , <protein>M-CSF receptor</protein> ( <protein>C-FMS</protein> ) , <dna>early growth response gene-1</dna> ( <dna>EGR-1</dna> ) and <dna>M-CSF genes</dna> in primary myelodysplastic syndromes ."}263{"id": "262", "text": "Peripheral blood mononuclear cells from seventeen patients with primary myelodysplastic syndromes ( MDS ) in advanced stage were enriched for blasts and tested for ( 1 ) karyotype , ( 2 ) genomic configuration and ( 3 ) expression of IL-3 , GM-CSF , FMS and EGR-1 genes which are all located on the long arm of chromosome 5 .", "annotated_text": "Peripheral blood mononuclear cells from seventeen patients with primary myelodysplastic syndromes ( MDS ) in advanced stage were enriched for <cell_type>blasts</cell_type> and tested for ( 1 ) karyotype , ( 2 ) genomic configuration and ( 3 ) expression of <dna>IL-3 , GM-CSF , FMS and EGR-1 genes</dna> which are all located on the <dna>long arm of chromosome 5</dna> ."}264{"id": "263", "text": "The expression of the M-CSF gene , that has been recently reassigned to the short arm of chromosome 1 ( lp ) , was also investigated .", "annotated_text": "The expression of the <dna>M-CSF gene</dna> , that has been recently reassigned to the <dna>short arm of chromosome 1</dna> ( <dna>lp</dna> ) , was also investigated ."}265{"id": "264", "text": "Aims of the study were to ( 1 ) assess the potential role of the expression of these genes in the maintenance and expansion of the neoplastic clones and ( 2 ) search for constitutional losses or rearrangements of one allele followed by a deletion of the second allele of the same genes in the leukemic cells .", "annotated_text": "Aims of the study were to ( 1 ) assess the potential role of the expression of these genes in the maintenance and expansion of the <cell_line>neoplastic clones</cell_line> and ( 2 ) search for constitutional losses or rearrangements of one <dna>allele</dna> followed by a deletion of the second <dna>allele</dna> of the same genes in the <cell_type>leukemic cells</cell_type> ."}266{"id": "265", "text": "The latter issue was investigated by comparing , in 8 cases , constitutive DNA from skin fibroblasts with leukemic DNA .", "annotated_text": "The latter issue was investigated by comparing , in 8 cases , <dna>constitutive DNA</dna> from <cell_type>skin fibroblasts</cell_type> with <dna>leukemic DNA</dna> ."}267{"id": "266", "text": "Eleven of the 17 patients had abnormal karyotypes .", "annotated_text": "Eleven of the 17 patients had abnormal karyotypes ."}268{"id": "267", "text": "The M-CSF gene was expressed in 6 cases and the FMS and the EGR-1 genes were expressed in 2 of the latter cases .", "annotated_text": "The <dna>M-CSF gene</dna> was expressed in 6 cases and the <dna>FMS</dna> and the <dna>EGR-1 genes</dna> were expressed in 2 of the latter cases ."}269{"id": "268", "text": "An autocrine mechanism of growth could be hypothesized only for the 2 patients whose cells expressed both the M-CSF and FMS genes .", "annotated_text": "An autocrine mechanism of growth could be hypothesized only for the 2 patients whose cells expressed both the <dna>M-CSF and FMS genes</dna> ."}270{"id": "269", "text": "No germline changes or rearrangements were observed in any of the genes studied .", "annotated_text": "No germline changes or rearrangements were observed in any of the genes studied ."}271{"id": "270", "text": "Thus , deregulation of genes encoding for certain hemopoietic growth factors or receptors does not seem to represent a major mechanism of MDS progression .", "annotated_text": "Thus , deregulation of genes encoding for certain <protein>hemopoietic growth factors</protein> or receptors does not seem to represent a major mechanism of MDS progression ."}272{"id": "271", "text": "A novel human homeobox gene distantly related to proboscipedia is expressed in lymphoid and pancreatic tissues .", "annotated_text": "A novel <dna>human homeobox gene</dna> distantly related to <dna>proboscipedia</dna> is expressed in lymphoid and pancreatic tissues ."}273{"id": "272", "text": "A novel human homeobox gene , HB9 , was isolated from a cDNA library prepared from in vitro stimulated human tonsil B lymphocytes and from a human genomic library .", "annotated_text": "A novel <dna>human homeobox gene</dna> , <dna>HB9</dna> , was isolated from a <dna>cDNA library</dna> prepared from in <cell_type>vitro stimulated human tonsil B lymphocytes</cell_type> and from a <dna>human genomic library</dna> ."}274{"id": "273", "text": "The HB9 gene is composed of 3 exons spread over 6 kilobases of DNA .", "annotated_text": "The <dna>HB9 gene</dna> is composed of 3 <dna>exons</dna> spread over 6 kilobases of DNA ."}275{"id": "274", "text": "An open reading frame of 1206 nucleotides is in frame with a diverged homeodomain .", "annotated_text": "An <dna>open reading frame</dna> of 1206 nucleotides is in frame with a <dna>diverged homeodomain</dna> ."}276{"id": "275", "text": "The predicted HB9 protein has a molecular mass of 41 kilodaltons and is enriched for alanine , glycine , and leucine .", "annotated_text": "The predicted <protein>HB9 protein</protein> has a molecular mass of 41 kilodaltons and is enriched for alanine , glycine , and leucine ."}277{"id": "276", "text": "The HB9 homeodomain is most similar to that of the Drosophila melanogaster homeobox gene proboscipedia .", "annotated_text": "The <dna>HB9 homeodomain</dna> is most similar to that of the <dna>Drosophila melanogaster homeobox gene</dna> <dna>proboscipedia</dna> ."}278{"id": "277", "text": "Northern blot analysis of poly ( A ) RNA purified from the human B cell line RPMI 8226 and from activated T cells revealed a major mRNA transcript of 2.2 kilobases .", "annotated_text": "Northern blot analysis of <rna>poly ( A ) RNA</rna> purified from the <cell_line>human B cell line RPMI 8226</cell_line> and from <cell_type>activated T cells</cell_type> revealed a <rna>major mRNA transcript</rna> of 2.2 kilobases ."}279{"id": "278", "text": "Similar analysis of poly ( A ) RNA from a variety of adult tissues demonstrated HB9 transcripts in pancreas , small intestine , and colon .", "annotated_text": "Similar analysis of <rna>poly ( A ) RNA</rna> from a variety of adult tissues demonstrated <dna>HB9</dna> transcripts in pancreas , small intestine , and colon ."}280{"id": "279", "text": "Reverse transcriptase-polymerase chain reaction was used to examine HB9 RNA transcripts in hematopoietic cell lines .", "annotated_text": "Reverse transcriptase-polymerase chain reaction was used to examine <rna>HB9 RNA transcripts</rna> in <cell_line>hematopoietic cell lines</cell_line> ."}281{"id": "280", "text": "HB9 RNA transcripts were most prevalent in several human B cell lines and K562 cells .", "annotated_text": "<rna>HB9 RNA transcripts</rna> were most prevalent in several <cell_line>human B cell lines</cell_line> and <cell_line>K562 cells</cell_line> ."}282{"id": "281", "text": "In addition , transcripts were detected in RNA prepared from tonsil B cells and in situ hybridization studies localized them in the germinal center region of adult tonsil .", "annotated_text": "In addition , transcripts were detected in RNA prepared from <cell_type>tonsil B cells</cell_type> and in situ hybridization studies localized them in the germinal center region of adult tonsil ."}283{"id": "282", "text": "These findings suggest the involvement of HB9 in regulating gene transcription in lymphoid and pancreatic tissues .", "annotated_text": "These findings suggest the involvement of <dna>HB9</dna> in regulating gene transcription in lymphoid and pancreatic tissues ."}284{"id": "283", "text": "Human immunodeficiency virus type 1 Tat upregulates interleukin-2 secretion in activated T cells .", "annotated_text": "<protein>Human immunodeficiency virus type 1 Tat</protein> upregulates <protein>interleukin-2</protein> secretion in <cell_type>activated T cells</cell_type> ."}285{"id": "284", "text": "Dysregulation of cytokines secreted by T cells may play an important role in the pathogenesis of AIDS .", "annotated_text": "Dysregulation of <protein>cytokines</protein> secreted by <cell_type>T cells</cell_type> may play an important role in the pathogenesis of AIDS ."}286{"id": "285", "text": "To investigate the effects of human immunodeficiency virus type 1 ( HIV-1 ) Tat on interleukin-2 ( IL-2 ) expression , we used IL-2 promoter-chloramphenicol acetyltransferase constructs and IL-2-secreting Jurkat T cells as a model system .", "annotated_text": "To investigate the effects of <protein>human immunodeficiency virus type 1 ( HIV-1 ) Tat</protein> on <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) expression , we used <dna>IL-2 promoter-chloramphenicol acetyltransferase constructs</dna> and <cell_line>IL-2-secreting Jurkat T cells</cell_line> as a model system ."}287{"id": "286", "text": "Transient expression of HIV-1 Tat induced a five- to eightfold increase in IL-2 promoter activity in Jurkat T cells stimulated with phytohemagglutinin and phorbol myristate acetate .", "annotated_text": "Transient expression of <protein>HIV-1 Tat</protein> induced a five- to eightfold increase in <dna>IL-2 promoter</dna> activity in <cell_line>Jurkat T cells</cell_line> stimulated with <protein>phytohemagglutinin</protein> and phorbol myristate acetate ."}288{"id": "287", "text": "IL-2 secretion was increased more than twofold in both Jurkat T cells and primary T cells stimulated by extracellular HIV-1 Tat protein .", "annotated_text": "<protein>IL-2</protein> secretion was increased more than twofold in both <cell_line>Jurkat T cells</cell_line> and <cell_line>primary T cells</cell_line> stimulated by <protein>extracellular HIV-1 Tat protein</protein> ."}289{"id": "288", "text": "Analysis of mRNA suggested that Tat exerts its effect on IL-2 primarily at the transcriptional level .", "annotated_text": "Analysis of <rna>mRNA</rna> suggested that Tat exerts its effect on <protein>IL-2</protein> primarily at the transcriptional level ."}290{"id": "289", "text": "The NF-kappa B site at positions -206 to -195 of the IL-2 promoter was required but not sufficient for the Tat effect .", "annotated_text": "The <dna>NF-kappa B site</dna> at positions <dna>-206 to -195</dna> of the <dna>IL-2 promoter</dna> was required but not sufficient for the <protein>Tat</protein> effect ."}291{"id": "290", "text": "The Tat -mediated increase in IL-2 promoter activity could selectively be blocked by antisense tat or-unlike the analogous effect of human T-cell lymphotropic virus type 1 Tax -by cyclosporin A .", "annotated_text": "The <protein>Tat</protein> -mediated increase in <dna>IL-2 promoter</dna> activity could selectively be blocked by antisense tat or-unlike the analogous effect of <protein>human T-cell lymphotropic virus type 1 Tax</protein> -by cyclosporin A ."}292{"id": "291", "text": "The observed increase in IL-2 levels might facilitate virus spread from or to T cells .", "annotated_text": "The observed increase in <protein>IL-2</protein> levels might facilitate virus spread from or to <cell_type>T cells</cell_type> ."}293{"id": "292", "text": "Furthermore , it might contribute to the hypergammaglobulinemia or , together with other cytokines found to be dysregulated , the T-helper cell dysfunctions observed in AIDS patients .", "annotated_text": "Furthermore , it might contribute to the hypergammaglobulinemia or , together with other <protein>cytokines</protein> found to be dysregulated , the T-helper cell dysfunctions observed in AIDS patients ."}294{"id": "293", "text": "Activation of nuclear factor kappa B in human lymphoblastoid cells by low-dose ionizing radiation .", "annotated_text": "Activation of <protein>nuclear factor kappa B</protein> in <cell_type>human lymphoblastoid cells</cell_type> by low-dose ionizing radiation ."}295{"id": "294", "text": "Nuclear factor kappa B ( NF-kappa B ) is a pleiotropic transcription factor which is involved in the transcriptional regulation of several specific genes .", "annotated_text": "<protein>Nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) is a <protein>pleiotropic transcription factor</protein> which is involved in the transcriptional regulation of several specific genes ."}296{"id": "295", "text": "Recent reports demonstrated that ionizing radiation in the dose range of 2-50 Gy results in expression of NF-kappa B in human KG-1 myeloid leukemia cells and human B-lymphocyte precursor cells ; the precise mechanism involved and the significance are not yet known .", "annotated_text": "Recent reports demonstrated that ionizing radiation in the dose range of 2-50 Gy results in expression of <protein>NF-kappa B</protein> in <cell_line>human KG-1 myeloid leukemia cells</cell_line> and <cell_type>human B-lymphocyte precursor cells</cell_type> ; the precise mechanism involved and the significance are not yet known ."}297{"id": "296", "text": "The present report demonstrates that even lower doses of ionizing radiation , 0.25-2.0 Gy , are capable of inducing expression of NF-kappa B in EBV-transformed 244B human lymphoblastoid cells .", "annotated_text": "The present report demonstrates that even lower doses of ionizing radiation , 0.25-2.0 Gy , are capable of inducing expression of <protein>NF-kappa B</protein> in <cell_line>EBV-transformed 244B human lymphoblastoid cells</cell_line> ."}298{"id": "297", "text": "These results are in a dose range where the viability of the cells remains very high .", "annotated_text": "These results are in a dose range where the viability of the cells remains very high ."}299{"id": "298", "text": "After exposure to 137Cs gamma rays at a dose rate of 1.17 Gy/min , a maximum in expression of NF-kappa B was seen at 8 h after a 0.5-Gy exposure .", "annotated_text": "After exposure to 137Cs gamma rays at a dose rate of 1.17 Gy/min , a maximum in expression of <protein>NF-kappa B</protein> was seen at 8 h after a 0.5-Gy exposure ."}300{"id": "299", "text": "Time-course studies revealed a biphasic time-dependent expression after 0.5- , 1- and 2-Gy exposures .", "annotated_text": "Time-course studies revealed a biphasic time-dependent expression after 0.5- , 1- and 2-Gy exposures ."}301{"id": "300", "text": "However , for each time examined , the expression of NF-kappa B was maximum after the 0.5-Gy exposure .", "annotated_text": "However , for each time examined , the expression of <protein>NF-kappa B</protein> was maximum after the 0.5-Gy exposure ."}302{"id": "301", "text": "The expression of the p50 and p65 NF-kappa B subunits was also shown to be regulated differentially after exposures to 1.0 and 2.0 Gy .", "annotated_text": "The expression of the <protein>p50 and p65 NF-kappa B subunits</protein> was also shown to be regulated differentially after exposures to 1.0 and 2.0 Gy ."}303{"id": "302", "text": "Alternative splicing of RNA transcripts encoded by the murine p105 NF-kappa B gene generates I kappa B gamma isoforms with different inhibitory activities .", "annotated_text": "Alternative splicing of <rna>RNA transcripts</rna> encoded by the <dna>murine p105 NF-kappa B gene</dna> generates <protein>I kappa B gamma isoforms</protein> with different inhibitory activities ."}304{"id": "303", "text": "The gene encoding the 105-kDa protein ( p105 ) precursor of the p50 subunit of transcription factor NF-kappa B also encodes a p70 I kappa B protein , I kappa B gamma , which is identical to the C-terminal 607 amino acids of p105 .", "annotated_text": "The gene encoding the <protein>105-kDa protein ( p105 ) precursor</protein> of the <protein>p50</protein> subunit of transcription factor <protein>NF-kappa B</protein> also encodes a <protein>p70 I kappa B protein</protein> , <protein>I kappa B gamma</protein> , which is identical to the <protein>C-terminal 607 amino acids</protein> of <protein>p105</protein> ."}305{"id": "304", "text": "Here we show that alternative RNA splicing generates I kappa B gamma isoforms with properties different from those of p70 .", "annotated_text": "Here we show that alternative RNA splicing generates <protein>I kappa B gamma isoforms</protein> with properties different from those of <protein>p70</protein> ."}306{"id": "305", "text": "One 63-kDa isoform , termed I kappa B gamma-1 , which lacks 59 amino acids C-terminal to ankyrin repeat 7 , has a novel 35-amino acid C terminus encoded by an alternative reading frame of the p105 gene .", "annotated_text": "One <protein>63-kDa isoform</protein> , termed <protein>I kappa B gamma-1</protein> , which lacks 59 amino acids C-terminal to <protein>ankyrin repeat 7</protein> , has a novel <protein>35-amino acid C terminus</protein> encoded by an <dna>alternative reading frame</dna> of the <dna>p105 gene</dna> ."}307{"id": "306", "text": "A 55-kDa isoform , I kappa B gamma-2 , lacks the 190 C-terminal amino acids of p70 I kappa B gamma .", "annotated_text": "A <protein>55-kDa isoform</protein> , <protein>I kappa B gamma-2</protein> , lacks the <protein>190 C-terminal amino acids</protein> of <protein>p70</protein> <protein>I kappa B gamma</protein> ."}308{"id": "307", "text": "In contrast to p70 I kappa B gamma , which is a cytoplasmic protein , I kappa B gamma-1 is found in both the cytoplasm and nucleus , whereas I kappa B gamma-2 is predominantly nuclear .", "annotated_text": "In contrast to <protein>p70</protein> <protein>I kappa B gamma</protein> , which is a <protein>cytoplasmic protein</protein> , <protein>I kappa B gamma-1</protein> is found in both the cytoplasm and nucleus , whereas <protein>I kappa B gamma-2</protein> is predominantly nuclear ."}309{"id": "308", "text": "The I kappa B gamma isoforms also display differences in specificity and affinity for Rel/NF-kappa B proteins .", "annotated_text": "The <protein>I kappa B gamma isoforms</protein> also display differences in specificity and affinity for <protein>Rel/NF-kappa B proteins</protein> ."}310{"id": "309", "text": "While p70 I kappa B gamma inhibits p50- , p65- , and c-Rel-mediated transactivation and/or DNA binding , both I kappa B gamma-1 and I kappa B gamma-2 are specific for p50 and have different affinities for this subunit .", "annotated_text": "While <protein>p70</protein> <protein>I kappa B gamma</protein> inhibits p50- , p65- , and c-Rel-mediated transactivation and/or DNA binding , both <protein>I kappa B gamma-1</protein> and <protein>I kappa B gamma-2</protein> are specific for <protein>p50</protein> and have different affinities for this subunit ."}311{"id": "310", "text": "The absence in I kappa B gamma-1 and I kappa B gamma-2 of a protein kinase A site whose phosphorylation modulates p70 I kappa B gamma inhibitory activity suggests that alternative RNA splicing may be used to generate I kappa B gamma isoforms that respond differently to intracellular signals .", "annotated_text": "The absence in <protein>I kappa B gamma-1</protein> and <protein>I kappa B gamma-2</protein> of a <dna>protein kinase A site</dna> whose phosphorylation modulates <protein>p70</protein> <protein>I kappa B gamma</protein> inhibitory activity suggests that alternative RNA splicing may be used to generate <protein>I kappa B gamma isoforms</protein> that respond differently to intracellular signals ."}312{"id": "311", "text": "Structure and expression of the human GATA3 gene .", "annotated_text": "Structure and expression of the <dna>human GATA3 gene</dna> ."}313{"id": "312", "text": "GATA3 , a member of the GATA family that is abundantly expressed in the T-lymphocyte lineage , is thought to participate in T-cell receptor gene activation through binding to enhancers .", "annotated_text": "<protein>GATA3</protein> , a member of the <protein>GATA family</protein> that is abundantly expressed in the <cell_type>T-lymphocyte lineage</cell_type> , is thought to participate in <protein>T-cell receptor</protein> gene activation through binding to <dna>enhancers</dna> ."}314{"id": "313", "text": "To understand GATA3 gene regulation , we cloned the human gene and the 5 ' end of the mouse GATA3 gene .", "annotated_text": "To understand <dna>GATA3 gene</dna> regulation , we cloned the <dna>human gene</dna> and the <dna>5 ' end</dna> of the <dna>mouse GATA3 gene</dna> ."}315{"id": "314", "text": "We show that the human GATA3 gene contains six exons distributed over 17 kb of DNA .", "annotated_text": "We show that the <dna>human GATA3 gene</dna> contains six <dna>exons</dna> distributed over 17 kb of DNA ."}316{"id": "315", "text": "The two human GATA3 zinc fingers are encoded by two separate exons highly conserved with those of GATA1 , but no other structural homologies between these two genes can be found .", "annotated_text": "The two <protein>human GATA3 zinc fingers</protein> are encoded by two separate <dna>exons</dna> highly conserved with those of <protein>GATA1</protein> , but no other structural homologies between these two genes can be found ."}317{"id": "316", "text": "The human and mouse GATA3 transcription units start at a major initiation site .", "annotated_text": "The <dna>human and mouse GATA3 transcription units</dna> start at a <dna>major initiation site</dna> ."}318{"id": "317", "text": "The promoter sequence analysis of these two genes revealed that they are embedded within a CpG island and share structural features often found in the promoters of housekeeping genes .", "annotated_text": "The promoter sequence analysis of these two genes revealed that they are embedded within a <dna>CpG island</dna> and share structural features often found in the <dna>promoters</dna> of <dna>housekeeping genes</dna> ."}319{"id": "318", "text": "Finally , we show that a DNA fragment containing the human GATA3 transcription unit , 3 kb upstream from the initiation site and 4 kb downstream from the polyadenylation site , displays T-cell specificity .", "annotated_text": "Finally , we show that a <dna>DNA fragment</dna> containing the <dna>human GATA3 transcription unit</dna> , <dna>3 kb upstream</dna> from the <dna>initiation site</dna> and <dna>4 kb downstream</dna> from the <dna>polyadenylation site</dna> , displays T-cell specificity ."}320{"id": "319", "text": "Characterization of the human gene encoding LBR , an integral protein of the nuclear envelope inner membrane .", "annotated_text": "Characterization of the <dna>human gene</dna> encoding <protein>LBR</protein> , an <protein>integral protein</protein> of the nuclear envelope inner membrane ."}321{"id": "320", "text": "We have characterized the human gene encoding LBR , an integral protein of the nuclear envelope inner membrane .", "annotated_text": "We have characterized the <dna>human gene</dna> encoding <protein>LBR</protein> , an <protein>integral protein</protein> of the nuclear envelope inner membrane ."}322{"id": "321", "text": "Restriction mapping shows that the transcription unit spans approximately 35 kilobases .", "annotated_text": "Restriction mapping shows that the <dna>transcription unit</dna> spans approximately 35 kilobases ."}323{"id": "322", "text": "A transcription start site is located approximately 4 kilobases 5 ' to the translation initiation codon , and an RNA splice of 3863 bases occurs in the 5'-untranslated region to generate mature HeLa cell mRNA .", "annotated_text": "A transcription start site is located approximately 4 kilobases 5 ' to the <dna>translation initiation codon</dna> , and an RNA splice of 3863 bases occurs in the <dna>5'-untranslated region</dna> to generate <rna>mature HeLa cell mRNA</rna> ."}324{"id": "323", "text": "5 ' to the identified transcription start site are two CCAAT sequences and potential recognition sites for several transcription factors including Sp1 , AP-1 , AP-2 , and NF-kB .", "annotated_text": "5 ' to the identified <dna>transcription start site</dna> are two <dna>CCAAT sequences</dna> and <dna>potential recognition sites</dna> for several <protein>transcription factors</protein> including <protein>Sp1</protein> , <protein>AP-1</protein> , <protein>AP-2</protein> , and <protein>NF-kB</protein> ."}325{"id": "324", "text": "There are 13 protein coding exons in the LBR gene .", "annotated_text": "There are 13 protein coding <dna>exons</dna> in the <dna>LBR gene</dna> ."}326{"id": "325", "text": "LBR 's nucleoplasmic domain is encoded by exons 1-4 , and its hydrophobic domain , with eight putative transmembrane segments , is encoded by exons 5-13 .", "annotated_text": "<protein>LBR</protein> 's <protein>nucleoplasmic domain</protein> is encoded by <dna>exons 1-4</dna> , and its <protein>hydrophobic domain</protein> , with eight putative <protein>transmembrane segments</protein> , is encoded by <dna>exons 5-13</dna> ."}327{"id": "326", "text": "The hydrophobic domain is homologous to three yeast polypeptides , suggesting that this higher eukaryotic gene could have evolved from recombination between a gene that encoded a soluble nuclear protein and a membrane protein gene similar to those in yeast .", "annotated_text": "The <protein>hydrophobic domain</protein> is homologous to three yeast polypeptides , suggesting that this <dna>higher eukaryotic gene</dna> could have evolved from recombination between a gene that encoded a <protein>soluble nuclear protein</protein> and a <dna>membrane protein gene</dna> similar to those in yeast ."}328{"id": "327", "text": "These results are the first to demonstrate the structural organization of a vertebrate gene encoding an integral membrane protein of the nuclear envelope that may be a member of a family of polypeptides conserved in evolution .", "annotated_text": "These results are the first to demonstrate the structural organization of a <dna>vertebrate gene</dna> encoding an <protein>integral membrane protein</protein> of the nuclear envelope that may be a member of a family of polypeptides conserved in evolution ."}329{"id": "328", "text": "Retinoic acid-induced expression of CD38 antigen in myeloid cells is mediated through retinoic acid receptor-alpha .", "annotated_text": "Retinoic acid-induced expression of <protein>CD38 antigen</protein> in <cell_type>myeloid cells</cell_type> is mediated through <protein>retinoic acid receptor-alpha</protein> ."}330{"id": "329", "text": "CD38 is a leukocyte differentiation antigen that has been thought to be a phenotypic marker of different subpopulations of T- and B- lymphocytes .", "annotated_text": "<protein>CD38</protein> is a <protein>leukocyte differentiation antigen</protein> that has been thought to be a phenotypic marker of different subpopulations of <cell_type>T- and B- lymphocytes</cell_type> ."}331{"id": "330", "text": "In myeloid cells , CD38 is expressed during early stages of differentiation .", "annotated_text": "In <cell_type>myeloid cells</cell_type> , <protein>CD38</protein> is expressed during early stages of differentiation ."}332{"id": "331", "text": "Virtually no information is available on regulation and functions of CD38 .", "annotated_text": "Virtually no information is available on regulation and functions of <protein>CD38</protein> ."}333{"id": "332", "text": "Recently we reported that all-trans-retinoic acid ( ATRA ) is a potent and highly specific inducer of CD38 expression in human promyelocytic leukemia cells .", "annotated_text": "Recently we reported that all-trans-retinoic acid ( ATRA ) is a potent and highly specific inducer of <protein>CD38</protein> expression in <cell_type>human promyelocytic leukemia cells</cell_type> ."}334{"id": "333", "text": "Here we report that ATRA-induced expression of CD38 antigen in myeloid cells is mediated through retinoic acid-alpha receptor ( RAR alpha ) .", "annotated_text": "Here we report that ATRA-induced expression of <protein>CD38 antigen</protein> in <cell_type>myeloid cells</cell_type> is mediated through <protein>retinoic acid-alpha receptor</protein> ( <protein>RAR alpha</protein> ) ."}335{"id": "334", "text": "ATRA failed to induce CD38 expression in a mutant subclone of the HL-60 myeloid leukemia cell line ( designated HL-60R ) that is relatively resistant to ATRA-induced granulocytic differentiation .", "annotated_text": "ATRA failed to induce <protein>CD38</protein> expression in a <cell_line>mutant subclone</cell_line> of the <cell_line>HL-60 myeloid leukemia cell line</cell_line> ( designated <cell_line>HL-60R</cell_line> ) that is relatively resistant to ATRA-induced granulocytic differentiation ."}336{"id": "335", "text": "Retroviral vector-mediated transduction of RA receptor ( RAR alpha ) into this HL-60R subclone completely restored the sensitivity of these cells to ATRA in terms of their ability to express CD38 .", "annotated_text": "Retroviral vector-mediated transduction of <protein>RA receptor</protein> ( <protein>RAR alpha</protein> ) into this <cell_line>HL-60R subclone</cell_line> completely restored the sensitivity of these cells to ATRA in terms of their ability to express <protein>CD38</protein> ."}337{"id": "336", "text": "In contrast , CD38 expression was not inducible by ATRA in HL-60R cells , transfected with a functional RAR beta , RAR gamma , or RXR alpha receptor .", "annotated_text": "In contrast , <protein>CD38</protein> expression was not inducible by ATRA in <cell_line>HL-60R cells</cell_line> , transfected with a functional <protein>RAR beta</protein> , <protein>RAR gamma</protein> , or <protein>RXR alpha receptor</protein> ."}338{"id": "337", "text": "Induction of CD38 in acute promyelocytic and acute myeloblastic leukemia cells was independent of ATRA-induced cytodifferentiation .", "annotated_text": "Induction of <protein>CD38</protein> in <cell_type>acute promyelocytic and acute myeloblastic leukemia cells</cell_type> was independent of ATRA-induced cytodifferentiation ."}339{"id": "338", "text": "Following culture with ATRA , increased CD38 protein levels were also observed in normal CD34+ bone marrow cells , but not on normal circulating granulocytes .", "annotated_text": "Following culture with ATRA , increased <protein>CD38</protein> protein levels were also observed in <cell_type>normal CD34+ bone marrow cells</cell_type> , but not on <cell_type>normal circulating granulocytes</cell_type> ."}340{"id": "339", "text": "From these results , we conclude that CD38 is ATRA inducible in myeloid leukemia cells and normal CD34+ bone marrow cells .", "annotated_text": "From these results , we conclude that <protein>CD38</protein> is ATRA inducible in <cell_type>myeloid leukemia cells</cell_type> and <cell_type>normal CD34+ bone marrow cells</cell_type> ."}341{"id": "340", "text": "This effect is independent of differentiation and is mediated by RAR alpha in HL-60 cells , suggesting a similar role for RAR alpha in CD38 expression in other hematopoietic cells .", "annotated_text": "This effect is independent of differentiation and is mediated by <protein>RAR alpha</protein> in <cell_type>HL-60 cells</cell_type> , suggesting a similar role for <protein>RAR alpha</protein> in <protein>CD38</protein> expression in other <cell_type>hematopoietic cells</cell_type> ."}342{"id": "341", "text": "Some antioxidants inhibit , in a co-ordinate fashion , the production of tumor necrosis factor-alpha , IL-beta , and IL-6 by human peripheral blood mononuclear cells .", "annotated_text": "Some antioxidants inhibit , in a co-ordinate fashion , the production of <protein>tumor necrosis factor-alpha</protein> , <protein>IL-beta</protein> , and <protein>IL-6</protein> by <cell_type>human peripheral blood mononuclear cells</cell_type> ."}343{"id": "342", "text": "Some antioxidants , including butylated hydroxyanisole ( BHA ) , tetrahydropapaveroline ( THP ) , nordihydroguiauretic acid , and 10 , 11-dihydroxyaporphine ( DHA ) , were found to be potent inhibitors of the production of tumor necrosis factor ( TNF ) -alpha , IL-1 beta , and IL-6 by human peripheral blood mononuclear cells ( PBMC ) stimulated by lipopolysaccharide ( LPS ) ( IC50s in the low micromolar range ) .", "annotated_text": "Some antioxidants , including butylated hydroxyanisole ( BHA ) , tetrahydropapaveroline ( THP ) , nordihydroguiauretic acid , and 10 , 11-dihydroxyaporphine ( DHA ) , were found to be potent inhibitors of the production of <protein>tumor necrosis factor ( TNF ) -alpha</protein> , <protein>IL-1 beta</protein> , and <protein>IL-6</protein> by <cell_type>human peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) stimulated by lipopolysaccharide ( LPS ) ( IC50s in the low micromolar range ) ."}344{"id": "343", "text": "Inhibition of cytokine production was gene selective and not due to general effects on protein synthesis .", "annotated_text": "Inhibition of <protein>cytokine</protein> production was gene selective and not due to general effects on protein synthesis ."}345{"id": "344", "text": "Inhibition of cytokine production by PBMC was observed also when other inducers were used ( staphylococci , silica , zymosan ) .", "annotated_text": "Inhibition of <protein>cytokine</protein> production by <cell_type>PBMC</cell_type> was observed also when other inducers were used ( staphylococci , silica , zymosan ) ."}346{"id": "345", "text": "Much higher concentrations of other antioxidants -- including ascorbic acid , trolox , alpha-tocopherol , butylated hydroxytoluene , and the 5-lipoxygenase inhibitor zileuton -- did not affect the production of these cytokines .", "annotated_text": "Much higher concentrations of other antioxidants -- including ascorbic acid , trolox , alpha-tocopherol , butylated hydroxytoluene , and the 5-lipoxygenase inhibitor zileuton -- did not affect the production of these <protein>cytokines</protein> ."}347{"id": "346", "text": "The active compounds did not inhibit IL-1 -induced production of IL-6 in fibroblasts , showing the cell selectivity of the effect .", "annotated_text": "The active compounds did not inhibit <protein>IL-1</protein> -induced production of <protein>IL-6</protein> in <cell_type>fibroblasts</cell_type> , showing the cell selectivity of the effect ."}348{"id": "347", "text": "Antioxidant-mediated inhibition of cytokine production was correlated with low levels of the corresponding messenger RNAs .", "annotated_text": "Antioxidant-mediated inhibition of <protein>cytokine</protein> production was correlated with low levels of the corresponding <rna>messenger RNAs</rna> ."}349{"id": "348", "text": "Nuclear run-on experiments showed that THP inhibited transcription of the IL-1 beta gene .", "annotated_text": "Nuclear run-on experiments showed that THP inhibited transcription of the <dna>IL-1 beta gene</dna> ."}350{"id": "349", "text": "THP decreased the concentration of the transcription factors NF-kappa B and AP-1 detected in nuclear extracts of PBMC cultured in the presence or absence of LPS .", "annotated_text": "THP decreased the concentration of the <protein>transcription factors</protein> <protein>NF-kappa B</protein> and <protein>AP-1</protein> detected in nuclear extracts of <cell_type>PBMC</cell_type> cultured in the presence or absence of LPS ."}351{"id": "350", "text": "THP and DHA markedly decreased the levels of TNF-alpha and IL-1 beta in the circulation of mice following LPS injection .", "annotated_text": "THP and DHA markedly decreased the levels of <protein>TNF-alpha</protein> and <protein>IL-1 beta</protein> in the circulation of mice following LPS injection ."}352{"id": "351", "text": "Thus antioxidants vary widely in potency as inhibitors of the activation of transcription factors and of the transcription of genes for pro-inflammatory cytokines .", "annotated_text": "Thus antioxidants vary widely in potency as inhibitors of the activation of <protein>transcription factors</protein> and of the transcription of <dna>genes</dna> for <protein>pro-inflammatory cytokines</protein> ."}353{"id": "352", "text": "Coordinate inhibition of the transcription of genes for inflammatory cytokines could provide a strategy for therapy of diseases with inflammatory pathogenesis and for septic shock .", "annotated_text": "Coordinate inhibition of the transcription of genes for inflammatory <protein>cytokines</protein> could provide a strategy for therapy of diseases with inflammatory pathogenesis and for septic shock ."}354{"id": "353", "text": "An interleukin-4-induced transcription factor : IL-4 Stat .", "annotated_text": "An <protein>interleukin-4-induced transcription factor</protein> : <protein>IL-4 Stat</protein> ."}355{"id": "354", "text": "Interleukin-4 ( IL-4 ) is an immunomodulatory cytokine secreted by activated T lymphocytes , basophils , and mast cells .", "annotated_text": "<protein>Interleukin-4</protein> ( <protein>IL-4</protein> ) is an immunomodulatory cytokine secreted by activated <cell_type>T lymphocytes</cell_type> , <cell_type>basophils</cell_type> , and <cell_type>mast cells</cell_type> ."}356{"id": "355", "text": "It plays an important role in modulating the balance of T helper ( Th ) cell subsets , favoring expansion of the Th2 lineage relative to Th1 .", "annotated_text": "It plays an important role in modulating the balance of <cell_type>T helper ( Th ) cell subsets</cell_type> , favoring expansion of the <cell_type>Th2 lineage</cell_type> relative to <cell_type>Th1</cell_type> ."}357{"id": "356", "text": "Imbalance of these T lymphocyte subsets has been implicated in immunological diseases including allergy , inflammation , and autoimmune disease .", "annotated_text": "Imbalance of these <cell_type>T lymphocyte subsets</cell_type> has been implicated in immunological diseases including allergy , inflammation , and autoimmune disease ."}358{"id": "357", "text": "IL-4 may mediate its biological effects , at least in part , by activating a tyrosine-phosphorylated DNA binding protein .", "annotated_text": "<protein>IL-4</protein> may mediate its biological effects , at least in part , by activating a <protein>tyrosine-phosphorylated DNA binding protein</protein> ."}359{"id": "358", "text": "This protein has now been purified and its encoding gene cloned .", "annotated_text": "This protein has now been purified and its encoding gene cloned ."}360{"id": "359", "text": "Examination of the primary amino acid sequence of this protein indicates that it is a member of the signal transducers and activators of transcription ( Stat ) family of DNA binding proteins , hereby designated IL-4 Stat .", "annotated_text": "Examination of the primary amino acid sequence of this protein indicates that it is a member of the <protein>signal transducers and activators of transcription ( Stat ) family</protein> of <protein>DNA binding proteins</protein> , hereby designated <protein>IL-4 Stat</protein> ."}361{"id": "360", "text": "Study of the inhibitory activities of phosphotyrosine-containing peptides derived from the intracellular domain of the IL-4 receptor provided evidence for direct coupling of receptor and transcription factor during the IL-4 Stat activation cycle .", "annotated_text": "Study of the inhibitory activities of phosphotyrosine-containing peptides derived from the <protein>intracellular domain of the IL-4 receptor</protein> provided evidence for direct coupling of <protein>receptor</protein> and <protein>transcription factor</protein> during the <protein>IL-4 Stat</protein> activation cycle ."}362{"id": "361", "text": "Such observations indicate that IL-4 Stat has the same functional domain for both receptor coupling and dimerization .", "annotated_text": "Such observations indicate that <protein>IL-4 Stat</protein> has the same <protein>functional domain</protein> for both receptor coupling and dimerization ."}363{"id": "362", "text": "Evaluation of the respiratory epithelium of normals and individuals with cystic fibrosis for the presence of adenovirus E1a sequences relevant to the use of E1a- adenovirus vectors for gene therapy for the respiratory manifestations of cystic fibrosis .", "annotated_text": "Evaluation of the respiratory epithelium of normals and individuals with cystic fibrosis for the presence of <dna>adenovirus E1a sequences</dna> relevant to the use of E1a- adenovirus vectors for gene therapy for the respiratory manifestations of cystic fibrosis ."}364{"id": "363", "text": "Lung disease associated with disorders such as cystic fibrosis ( CF ) may be amenable to somatic gene therapy in which there is delivery of the normal gene directly to the respiratory epithelium using E1a- adenovirus ( Ad ) type 2- or 5-based vectors .", "annotated_text": "Lung disease associated with disorders such as cystic fibrosis ( CF ) may be amenable to somatic gene therapy in which there is delivery of the <dna>normal gene</dna> directly to the respiratory epithelium using E1a- adenovirus ( Ad ) type 2- or 5-based vectors ."}365{"id": "364", "text": "For safety reasons , the Ad vectors are rendered replication deficient by deletion of the E1a region .", "annotated_text": "For safety reasons , the Ad vectors are rendered replication deficient by deletion of the <dna>E1a region</dna> ."}366{"id": "365", "text": "Because there is the theoretical possibility of an E1a- replication-deficient vector replicating as a result of recombination or complementation with Ad 2/5 E1a sequences present in the target cell , this study is directed toward evaluating respiratory epithelium of normals and individuals with CF for the presence of E1a sequences .", "annotated_text": "Because there is the theoretical possibility of an E1a- replication-deficient vector replicating as a result of recombination or complementation with <dna>Ad 2/5 E1a sequences</dna> present in the target cell , this study is directed toward evaluating respiratory epithelium of normals and individuals with CF for the presence of E1a sequences ."}367{"id": "366", "text": "Using Ad 2/5 E1a-specific primers and the polymerase chain reaction to evaluate DNA recovered from freshly isolated nasal and bronchial epithelium recovered by brushing , E1a sequences were detected in respiratory epithelium of 19 of 91 normals ( 21 % ) .", "annotated_text": "Using <dna>Ad 2/5 E1a-specific primers</dna> and the polymerase chain reaction to evaluate DNA recovered from freshly isolated nasal and bronchial epithelium recovered by brushing , <dna>E1a sequences</dna> were detected in respiratory epithelium of 19 of 91 normals ( 21 % ) ."}368{"id": "367", "text": "In the E1a-positive samples , the average of E1a copy number was 55 +/- 18/10 ( 3 ) recovered cells .", "annotated_text": "In the E1a-positive samples , the average of E1a copy number was 55 +/- 18/10 ( 3 ) recovered cells ."}369{"id": "368", "text": "In CF individuals , 7 of 52 ( 13 % ) had detectable E1a sequences in the respiratory epithelium , with E1a copy number in the positive samples of 80 +/- 21/10 ( 3 ) recovered cells .", "annotated_text": "In CF individuals , 7 of 52 ( 13 % ) had detectable <dna>E1a sequences</dna> in the respiratory epithelium , with E1a copy number in the positive samples of 80 +/- 21/10 ( 3 ) recovered cells ."}370{"id": "369", "text": "These results demonstrate that there are detectable Ad 2/5 E1a sequences in the respiratory epithelium of a small percentage of normals and individuals with CF .", "annotated_text": "These results demonstrate that there are detectable <dna>Ad 2/5 E1a sequences</dna> in the respiratory epithelium of a small percentage of normals and individuals with CF ."}371{"id": "370", "text": "Because of the theoretical potential of such sequences supporting replication of E1a- Ad vectors , human gene therapy protocols for CF utilizing such vectors should consider evaluating study individuals for the presence of Ad 2/5 E1a sequences in the respiratory epithelium .", "annotated_text": "Because of the theoretical potential of such sequences supporting replication of E1a- Ad vectors , human gene therapy protocols for CF utilizing such vectors should consider evaluating study individuals for the presence of <dna>Ad 2/5 E1a sequences</dna> in the respiratory epithelium ."}372{"id": "371", "text": "Leiomyosarcoma of the vulva : report of a case .", "annotated_text": "Leiomyosarcoma of the vulva : report of a case ."}373{"id": "372", "text": "A 52-year-old female presented with a progressively enlarging vulvar mass .", "annotated_text": "A 52-year-old female presented with a progressively enlarging vulvar mass ."}374{"id": "373", "text": "Pathological evaluation revealed a high-grade vulvar leiomyosarcoma .", "annotated_text": "Pathological evaluation revealed a high-grade vulvar leiomyosarcoma ."}375{"id": "374", "text": "Immunohistochemical and ultrastructural studies were performed to support the diagnosis .", "annotated_text": "Immunohistochemical and ultrastructural studies were performed to support the diagnosis ."}376{"id": "375", "text": "In an effort to better understand the biology of this tumor additional immunohistochemical studies for the protein product of p53 tumor suppressor gene and estrogen receptor expression by tumor cells , as well as the type of immune cells infiltrating the tumor were performed .", "annotated_text": "In an effort to better understand the biology of this tumor additional immunohistochemical studies for the <protein>protein product</protein> of <dna>p53 tumor suppressor gene</dna> and <protein>estrogen receptor</protein> expression by <cell_type>tumor cells</cell_type> , as well as the type of <cell_type>immune cells</cell_type> infiltrating the tumor were performed ."}377{"id": "376", "text": "Tumor cells showed an overexpression of p53 protein and were estrogen receptor -positive .", "annotated_text": "<cell_type>Tumor cells</cell_type> showed an overexpression of <protein>p53 protein</protein> and were <protein>estrogen receptor</protein> -positive ."}378{"id": "377", "text": "Macrophages and T and B lymphocytes infiltrated the tumor in moderate numbers with occasional lymphoid aggregate formation .", "annotated_text": "<cell_type>Macrophages</cell_type> and <cell_type>T and B lymphocytes</cell_type> infiltrated the tumor in moderate numbers with occasional lymphoid aggregate formation ."}379{"id": "378", "text": "This study is the first attempt to better understand the biology of these tumors .", "annotated_text": "This study is the first attempt to better understand the biology of these tumors ."}380{"id": "379", "text": "Stimulation of HIV replication in mononuclear phagocytes by leukemia inhibitory factor .", "annotated_text": "Stimulation of HIV replication in <cell_type>mononuclear phagocytes</cell_type> by <protein>leukemia inhibitory factor</protein> ."}381{"id": "380", "text": "This study examined the effects of leukemia inhibitory factor ( LIF ) on human immunodeficiency virus ( HIV ) replication in mononuclear phagocytes ( MNP ) .", "annotated_text": "This study examined the effects of <protein>leukemia inhibitory factor</protein> ( <protein>LIF</protein> ) on human immunodeficiency virus ( HIV ) replication in <cell_type>mononuclear phagocytes</cell_type> ( <cell_type>MNP</cell_type> ) ."}382{"id": "381", "text": "LIF induced a dose-dependent increase in p24 antigen production in the chronically infected promonocytic cell line U1 .", "annotated_text": "<protein>LIF</protein> induced a dose-dependent increase in <protein>p24 antigen</protein> production in the <cell_line>chronically infected promonocytic cell line U1</cell_line> ."}383{"id": "382", "text": "The magnitude and time kinetics of the LIF effects were similar to interleukin 1 ( IL-1 ) , IL-6 , and tumor necrosis factor ( TNF ) , other cytokines known to induce HIV replication in this cell line .", "annotated_text": "The magnitude and time kinetics of the <protein>LIF</protein> effects were similar to <protein>interleukin 1</protein> ( <protein>IL-1</protein> ) , <protein>IL-6</protein> , and <protein>tumor necrosis factor</protein> ( <protein>TNF</protein> ) , other cytokines known to induce HIV replication in this cell line ."}384{"id": "383", "text": "To characterize mechanisms responsible for these LIF effects , levels of HIV mRNA , activation of the DNA binding protein nuclear factor ( NF ) -kB , signal transduction pathways , and potential interactions with other cytokines were analyzed .", "annotated_text": "To characterize mechanisms responsible for these <protein>LIF</protein> effects , levels of <rna>HIV mRNA</rna> , activation of the <protein>DNA binding protein nuclear factor</protein> <protein>( NF ) -kB</protein> , signal transduction pathways , and potential interactions with other <protein>cytokines</protein> were analyzed ."}385{"id": "384", "text": "LIF increased steady-state levels of HIV mRNA at 2.0 , 4.3 , and 9.2 kB .", "annotated_text": "<protein>LIF</protein> increased steady-state levels of <rna>HIV mRNA</rna> at 2.0 , 4.3 , and 9.2 kB ."}386{"id": "385", "text": "This was detectable by 24 h and persisted until 72 h .", "annotated_text": "This was detectable by 24 h and persisted until 72 h ."}387{"id": "386", "text": "The DNA binding protein NF-kB is a central mediator in cytokine activation of HIV transcription .", "annotated_text": "The <protein>DNA binding protein NF-kB</protein> is a central mediator in <protein>cytokine</protein> activation of HIV transcription ."}388{"id": "387", "text": "NF-kB levels were higher in unstimulated U1 cells as compared to the parent cell line U937 .", "annotated_text": "<protein>NF-kB</protein> levels were higher in <cell_line>unstimulated U1 cells</cell_line> as compared to the <cell_line>parent cell line</cell_line> <cell_line>U937</cell_line> ."}389{"id": "388", "text": "In both cell lines LIF increased NF-kB activity .", "annotated_text": "In both cell lines <protein>LIF</protein> increased <protein>NF-kB</protein> activity ."}390{"id": "389", "text": "Induction of NF-kB and HIV replication by cytokines are at least in part dependent on reactive oxygen intermediates .", "annotated_text": "Induction of <protein>NF-kB</protein> and HIV replication by <protein>cytokines</protein> are at least in part dependent on reactive oxygen intermediates ."}391{"id": "390", "text": "The oxygen radical scavenger N-acetyl-L-cysteine , but not an inhibitor of nitric oxide synthase , inhibited LIF -induced HIV replication .", "annotated_text": "The oxygen radical scavenger N-acetyl-L-cysteine , but not an inhibitor of <protein>nitric oxide synthase</protein> , inhibited <protein>LIF</protein> -induced HIV replication ."}392{"id": "391", "text": "LIF induces the production of other cytokines in monocytes but its effects on HIV replication were not inhibited by antibodies to IL-1 , TNF , or IL-6 .", "annotated_text": "<protein>LIF</protein> induces the production of other <protein>cytokines</protein> in monocytes but its effects on HIV replication were not inhibited by <protein>antibodies</protein> to <protein>IL-1</protein> , <protein>TNF</protein> , or <protein>IL-6</protein> ."}393{"id": "392", "text": "These results identify LIF as a stimulus of HIV replication .", "annotated_text": "These results identify <protein>LIF</protein> as a stimulus of HIV replication ."}394{"id": "393", "text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"}395{"id": "394", "text": "Mechanisms involved in the inhibition of growth of a human B lymphoma cell line , B104 , by anti-MHC class II antibodies .", "annotated_text": "Mechanisms involved in the inhibition of growth of a <cell_line>human B lymphoma cell line</cell_line> , <cell_line>B104</cell_line> , by <protein>anti-MHC class II antibodies</protein> ."}396{"id": "395", "text": "The mechanisms involved in the inhibition of growth of a human B lymphoma cell line , B104 , by anti-MHC class II antibodies ( Ab ) were compared with those in anti-IgM Ab -induced B104 growth inhibition .", "annotated_text": "The mechanisms involved in the inhibition of growth of a <cell_line>human B lymphoma cell line</cell_line> , <cell_line>B104</cell_line> , by <protein>anti-MHC class II antibodies</protein> ( <protein>Ab</protein> ) were compared with those in <protein>anti-IgM Ab</protein> -induced B104 growth inhibition ."}397{"id": "396", "text": "Two anti-MHC class II Ab , L227 and 2.06 , inhibited the growth of B104 cells , although 2.06 , but not L227 , needed to be further cross-linked with a goat anti-mouse IgG Ab ( GAM ) to show the effect .", "annotated_text": "Two <protein>anti-MHC class II Ab</protein> , <protein>L227</protein> and <protein>2.06</protein> , inhibited the growth of <cell_line>B104 cells</cell_line> , although <protein>2.06</protein> , but not <protein>L227</protein> , needed to be further cross-linked with a <protein>goat anti-mouse IgG Ab</protein> ( <protein>GAM</protein> ) to show the effect ."}398{"id": "397", "text": "L227 induced an increase in intracellular free Ca2+ concentration ( [ Ca2+ ] i ) from the intracellular pool and little or no protein tyrosine phosphorylation , phosphatidyl inositol turnover , or expression of Egr-1 mRNA , whereas 2.06 plus GAM induced an increase in [ Ca2+ ] i from both the intracellular and , in particular , the extracellular pools .", "annotated_text": "<protein>L227</protein> induced an increase in intracellular free Ca2+ concentration ( [ Ca2+ ] i ) from the intracellular pool and little or no protein tyrosine phosphorylation , phosphatidyl inositol turnover , or expression of <rna>Egr-1 mRNA</rna> , whereas <protein>2.06</protein> plus <protein>GAM</protein> induced an increase in [ Ca2+ ] i from both the intracellular and , in particular , the extracellular pools ."}399{"id": "398", "text": "The inhibition of B104 cell growth induced by anti-MHC class II Ab was Ca ( 2+ ) -independent and not inhibited by actinomycin D or cyclosporin A , and cell cycle arrest at the G2/M interphase was not observed .", "annotated_text": "The inhibition of <cell_line>B104 cell</cell_line> growth induced by <protein>anti-MHC class II Ab</protein> was Ca ( 2+ ) -independent and not inhibited by actinomycin D or cyclosporin A , and cell cycle arrest at the G2/M interphase was not observed ."}400{"id": "399", "text": "These features are very different from those observed in B104 cell death induced by anti-IgM Ab .", "annotated_text": "These features are very different from those observed in <cell_line>B104 cell</cell_line> death induced by <protein>anti-IgM Ab</protein> ."}401{"id": "400", "text": "Neither DNA fragmentation nor the morphology of apoptosis was observed .", "annotated_text": "Neither DNA fragmentation nor the morphology of apoptosis was observed ."}402{"id": "401", "text": "These findings demonstrate that cross-linking of MHC class II molecules transduced the negative signals through intracellular mechanisms different from those present in the cross-linking of surface IgM .", "annotated_text": "These findings demonstrate that cross-linking of <protein>MHC class II molecules</protein> transduced the negative signals through intracellular mechanisms different from those present in the cross-linking of surface <protein>IgM</protein> ."}403{"id": "402", "text": "Functional block for 1 alpha , 25-dihydroxyvitamin D3-mediated gene regulation in human B lymphocytes .", "annotated_text": "Functional block for 1 alpha , 25-dihydroxyvitamin D3-mediated gene regulation in <cell_type>human B lymphocytes</cell_type> ."}404{"id": "403", "text": "Elements necessary for the steroid hormone 1 alpha , 25-dihydroxyvitamin D3 ( 1 alpha , 25- ( OH ) 2D3 ) to induce a biological response include the presence of specific intracellular receptors ( vitamin D3 receptors ( VDR ) ) and modulation of gene expression via hormone-activated receptor binding to regulatory regions of target genes .", "annotated_text": "Elements necessary for the steroid hormone 1 alpha , 25-dihydroxyvitamin D3 ( 1 alpha , 25- ( OH ) 2D3 ) to induce a biological response include the presence of specific <protein>intracellular receptors</protein> ( <protein>vitamin D3 receptors</protein> ( <protein>VDR</protein> ) ) and modulation of gene expression via hormone-activated receptor binding to <protein>regulatory regions</protein> of <dna>target genes</dna> ."}405{"id": "404", "text": "These parameters were examined in normal and Epstein-Barr virus-immortalized human B cells and compared with 1 alpha , 25- ( OH ) 2D3-responsive cells of the T and monocytic lineages .", "annotated_text": "These parameters were examined in normal and <cell_line>Epstein-Barr virus-immortalized human B cells</cell_line> and compared with <cell_line>1 alpha , 25- ( OH ) 2D3-responsive cells</cell_line> of the <cell_type>T and monocytic lineages</cell_type> ."}406{"id": "405", "text": "Although resting tonsillar B cells did not express VDR mRNA , activation of these cells with interleukin-4 induced VDR in the absence of exogenously supplemented 1 alpha , 25- ( OH ) 2D3 .", "annotated_text": "Although resting tonsillar B cells did not express <rna>VDR mRNA</rna> , activation of these cells with <protein>interleukin-4</protein> induced <protein>VDR</protein> in the absence of exogenously supplemented 1 alpha , 25- ( OH ) 2D3 ."}407{"id": "406", "text": "As indicators of hormone-mediated gene regulation we analyzed modulation of CD23 , a common B cell/monocyte surface antigen , and 24-hydroxylase .", "annotated_text": "As indicators of hormone-mediated gene regulation we analyzed modulation of <protein>CD23</protein> , a <protein>common B cell/monocyte surface antigen</protein> , and <protein>24-hydroxylase</protein> ."}408{"id": "407", "text": "1 alpha , 25- ( OH ) 2D3 inhibited CD23 expression in U937 cells , yet failed to modulate CD23 expression in B cells .", "annotated_text": "1 alpha , 25- ( OH ) 2D3 inhibited <protein>CD23</protein> expression in <cell_line>U937 cells</cell_line> , yet failed to modulate <protein>CD23</protein> expression in <cell_type>B cells</cell_type> ."}409{"id": "408", "text": "Furthermore , 1 alpha , 25- ( OH ) 2D3 induced 24-hydroxylase mRNA expression and metabolic activity in both U937 cells and lectin-activated T cells , yet failed to induce 24-hydroxylase mRNA or its metabolic activity in B cells .", "annotated_text": "Furthermore , 1 alpha , 25- ( OH ) 2D3 induced <protein>24-hydroxylase</protein> mRNA expression and metabolic activity in both <cell_line>U937 cells</cell_line> and <cell_type>lectin-activated T cells</cell_type> , yet failed to induce <rna>24-hydroxylase mRNA</rna> or its metabolic activity in <cell_type>B cells</cell_type> ."}410{"id": "409", "text": "These findings suggest that although human B lymphocytes can express VDR mRNA and protein , they exhibit a functional block for vitamin D-dependent gene regulation .", "annotated_text": "These findings suggest that although <cell_type>human B lymphocytes</cell_type> can express <rna>VDR mRNA</rna> and <protein>protein</protein> , they exhibit a functional block for vitamin D-dependent gene regulation ."}411{"id": "410", "text": "Positive and negative regulation of IL-2 gene expression : role of multiple regulatory sites .", "annotated_text": "Positive and negative regulation of <protein>IL-2</protein> gene expression : role of multiple regulatory sites ."}412{"id": "411", "text": "Interleukin 2 ( IL-2 ) is an important lymphokine required in the process of T cell activation , proliferation , clonal expansion and differentiation .", "annotated_text": "Interleukin 2 ( <protein>IL-2</protein> ) is an important <protein>lymphokine</protein> required in the process of T cell activation , proliferation , clonal expansion and differentiation ."}413{"id": "412", "text": "The IL-2 gene displays both T cell specific and inducible expression : it is only expressed in CD4+ T cells after antigenic or mitogenic stimulation .", "annotated_text": "The <dna>IL-2 gene</dna> displays both T cell specific and inducible expression : it is only expressed in <cell_type>CD4+ T cells</cell_type> after antigenic or mitogenic stimulation ."}414{"id": "413", "text": "Several cis-acting regulatory sites are required for induction of the IL-2 gene after stimulation .", "annotated_text": "Several <dna>cis-acting regulatory sites</dna> are required for induction of the <dna>IL-2 gene</dna> after stimulation ."}415{"id": "414", "text": "In this study , we have analysed the function of these cis-acting regulatory sites in the context of the native IL-2 enhancer and promoter sequence .", "annotated_text": "In this study , we have analysed the function of these <dna>cis-acting regulatory sites</dna> in the context of the native <dna>IL-2 enhancer</dna> and <dna>promoter sequence</dna> ."}416{"id": "415", "text": "The results of this study suggest that the NFAT ( -276 to -261 ) , the distal octamer ( -256 to -248 ) and the proximal octamer ( -75 to -66 ) sites not only act as enhancers of IL-2 gene transcription in the presence of cellular stimulation , but also have a silencing effect on IL-2 gene expression in resting cells .", "annotated_text": "The results of this study suggest that the <protein>NFAT</protein> ( <dna>-276 to -261</dna> ) , the <dna>distal octamer</dna> ( <dna>-256 to -248</dna> ) and the <dna>proximal octamer</dna> ( <dna>-75 to -66</dna> ) sites not only act as enhancers of <dna>IL-2 gene</dna> transcription in the presence of cellular stimulation , but also have a silencing effect on <dna>IL-2 gene</dna> expression in resting cells ."}417{"id": "416", "text": "Two other sites display disparate effects on IL-2 gene expression in different T leukemia cell lines : the distal purine box ( -291 to -277 ) and the proximal purine box sites ( -145 to -128 ) .", "annotated_text": "Two other sites display disparate effects on <dna>IL-2 gene</dna> expression in different <cell_line>T leukemia cell lines</cell_line> : the <dna>distal purine box</dna> ( <dna>-291 to -277</dna> ) and the <dna>proximal purine box sites</dna> ( <dna>-145 to -128</dna> ) ."}418{"id": "417", "text": "Finally , the AP-1 ( -186 to -176 ) and the kappa B sites ( -206 to -195 ) respond to different cellular activation in EL4 cells .", "annotated_text": "Finally , the <dna>AP-1 ( -186 to -176 ) and the kappa B sites</dna> ( <dna>-206 to -195</dna> ) respond to different cellular activation in <cell_line>EL4 cells</cell_line> ."}419{"id": "418", "text": "The AP-1 site mediated the response to PMA stimulation while the kappa B site responded to IL-1 stimulation .", "annotated_text": "The <dna>AP-1 site</dna> mediated the response to PMA stimulation while the <dna>kappa B site</dna> responded to <protein>IL-1</protein> stimulation ."}420{"id": "419", "text": "These data suggest that the regulation of IL-2 gene expression is a complex process and multiple cis-acting regulatory sites interact to exert different effects in T cells representative of alternative stages of differentiation .", "annotated_text": "These data suggest that the regulation of <dna>IL-2 gene</dna> expression is a complex process and multiple <dna>cis-acting regulatory sites</dna> interact to exert different effects in <cell_type>T cells</cell_type> representative of alternative stages of differentiation ."}421{"id": "420", "text": "Sp1 is a critical factor for the monocytic specific expression of human CD14 .", "annotated_text": "<protein>Sp1</protein> is a critical factor for the monocytic specific expression of <protein>human CD14</protein> ."}422{"id": "421", "text": "CD14 is a membrane glycoprotein expressed specifically on monocytes and macrophages , and its expression is markedly increased during the process of monocyte differentiation .", "annotated_text": "<protein>CD14</protein> is a <protein>membrane glycoprotein</protein> expressed specifically on <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> , and its expression is markedly increased during the process of <cell_type>monocyte</cell_type> differentiation ."}423{"id": "422", "text": "In order to study CD14 gene regulation , the human CD14 gene was cloned from a partial EcoRI digested chromosome 5 library .", "annotated_text": "In order to study <dna>CD14 gene</dna> regulation , the <dna>human CD14 gene</dna> was cloned from a partial <dna>EcoRI digested chromosome 5 library</dna> ."}424{"id": "423", "text": "A 5.5-kilobase genomic clone contained the full-length CD14 coding sequence and 4.2 kilobases of 5'-upstream sequence .", "annotated_text": "A <dna>5.5-kilobase genomic clone</dna> contained the full-length <dna>CD14 coding sequence</dna> and <dna>4.2 kilobases of 5'-upstream sequence</dna> ."}425{"id": "424", "text": "One major and one minor transcription start site were identified 101 and 130 base pairs ( bp ) upstream , respectively , from the protein translation start ATG .", "annotated_text": "One <dna>major and one minor transcription start site</dna> were identified <dna>101 and 130 base pairs ( bp ) upstream</dna> , respectively , from the <dna>protein translation start ATG</dna> ."}426{"id": "425", "text": "A DNA fragment containing 128 bp of upstream sequence had strong , monocyte-specific promoter activity in the CD14 positive monocytic cell line Mono Mac 6 as compared to the nonmonocytic cell lines HeLa and REX .", "annotated_text": "A <dna>DNA fragment</dna> containing <dna>128 bp of upstream sequence</dna> had strong , monocyte-specific promoter activity in the <cell_line>CD14 positive monocytic cell line</cell_line> <cell_line>Mono Mac 6</cell_line> as compared to the <cell_line>nonmonocytic cell lines</cell_line> <cell_line>HeLa</cell_line> and <cell_line>REX</cell_line> ."}427{"id": "426", "text": "Four regions in this DNA fragment interact with nuclear proteins isolated from monocytic cells .", "annotated_text": "Four regions in this <dna>DNA fragment</dna> interact with <protein>nuclear proteins</protein> isolated from <cell_type>monocytic cells</cell_type> ."}428{"id": "427", "text": "The Sp1 transcription factor bound to three different regions in the CD14 promoter .", "annotated_text": "The <protein>Sp1</protein> <protein>transcription factor</protein> bound to three different regions in the <dna>CD14 promoter</dna> ."}429{"id": "428", "text": "Mutation of the major Sp1 binding site ( -110 bp ) decreased tissue-specific promoter activity , and these results , together with transactivation experiments , demonstrate that Sp1 plays a critical role in the tissue-specific expression of CD14 in monocytic cells .", "annotated_text": "Mutation of the <dna>major Sp1 binding site</dna> ( <dna>-110 bp</dna> ) decreased tissue-specific promoter activity , and these results , together with transactivation experiments , demonstrate that <protein>Sp1</protein> plays a critical role in the tissue-specific expression of <protein>CD14</protein> in <cell_type>monocytic cells</cell_type> ."}430{"id": "429", "text": "CD14 Sp1 site oligonucleotides bound preferentially to a 105-kDa Sp1 species , which is present in higher relative levels in monocytic than non-monocytic cells , suggesting that modification of Sp1 , such as phosphorylation , may explain how the Sp1 site mediates monocytic specific promoter activity .", "annotated_text": "<protein>CD14</protein> <protein>Sp1</protein> site oligonucleotides bound preferentially to a <protein>105-kDa Sp1 species</protein> , which is present in higher relative levels in <cell_type>monocytic</cell_type> than <cell_type>non-monocytic cells</cell_type> , suggesting that modification of <protein>Sp1</protein> , such as phosphorylation , may explain how the <protein>Sp1</protein> site mediates monocytic specific promoter activity ."}431{"id": "430", "text": "The interleukin-8 AP-1 and kappa B-like sites are genetic end targets of FK506-sensitive pathway accompanied by calcium mobilization .", "annotated_text": "The <dna>interleukin-8 AP-1 and kappa B-like sites</dna> are genetic end targets of FK506-sensitive pathway accompanied by calcium mobilization ."}432{"id": "431", "text": "FK506 , an immunosuppressant , inhibits the production of several cytokines in T lymphocytes .", "annotated_text": "FK506 , an immunosuppressant , inhibits the production of several <protein>cytokines</protein> in <cell_type>T lymphocytes</cell_type> ."}433{"id": "432", "text": "We observed that FK506 suppressed the transcription of a chemotactic cytokine , interleukin-8 ( IL-8 ) in a human T cell line , Jurkat cells , activated by phorbol 12-myristate 13-acetate ( PMA ) and calcium ( Ca2+ ) ionophore ( ionomycin ) .", "annotated_text": "We observed that FK506 suppressed the transcription of a <protein>chemotactic cytokine</protein> , <protein>interleukin-8</protein> ( <protein>IL-8</protein> ) in a <cell_line>human T cell line</cell_line> , <cell_line>Jurkat cells</cell_line> , activated by phorbol 12-myristate 13-acetate ( PMA ) and calcium ( Ca2+ ) ionophore ( ionomycin ) ."}434{"id": "433", "text": "By deleted and mutated analysis of the IL-8 promoters , the AP-1 and kappa B-like sites were identified as the responsive elements for PMA and ionomycin .", "annotated_text": "By deleted and mutated analysis of the <dna>IL-8 promoters</dna> , the <dna>AP-1 and kappa B-like sites</dna> were identified as the responsive elements for PMA and ionomycin ."}435{"id": "434", "text": "FK506 suppressed the transcriptions through the AP-1 or kappa B-like sites induced by PMA plus Ca ( 2+ ) -mobilizing agents , but not those induced by Ca ( 2+ ) -independent stimuli .", "annotated_text": "FK506 suppressed the transcriptions through the <dna>AP-1</dna> or <dna>kappa B-like sites</dna> induced by PMA plus Ca ( 2+ ) -mobilizing agents , but not those induced by Ca ( 2+ ) -independent stimuli ."}436{"id": "435", "text": "In gel retardation analysis , FK506 had little effect on the binding to the AP-1 site of PMA/ionomycin-induced nuclear factors , which were recognized with anti-JunD or c-Fos antibody .", "annotated_text": "In gel retardation analysis , FK506 had little effect on the binding to the <dna>AP-1 site</dna> of PMA/ionomycin-induced nuclear factors , which were recognized with <protein>anti-JunD</protein> or <protein>c-Fos antibody</protein> ."}437{"id": "436", "text": "In contrast , FK506 or EGTA ( Ca2+ chelator ) similarly affected the formation of kappa B-like site binding complexes , which were not recognized by any antibodies against the human Rel family proteins ( c-Rel , p65 , p50 , and p49 ) .", "annotated_text": "In contrast , FK506 or EGTA ( Ca2+ chelator ) similarly affected the formation of <protein>kappa B-like site binding complexes</protein> , which were not recognized by any <protein>antibodies</protein> against the <protein>human Rel family proteins</protein> ( <protein>c-Rel</protein> , <protein>p65</protein> , <protein>p50</protein> , and <protein>p49</protein> ) ."}438{"id": "437", "text": "Furthermore , we confirmed the previous report that FK506 suppressed the PMA/ionomycin-induced activation through authentic kappa B site of immunoglobulin ( Ig ) gene , to which NF-kappa B binding was also decreased by FK506 , indicating that both IL-8 kappa B-like site and Ig kappa B site are FK506-sensitive in spite of the difference of binding factors .", "annotated_text": "Furthermore , we confirmed the previous report that FK506 suppressed the PMA/ionomycin-induced activation through authentic <dna>kappa B site</dna> of <dna>immunoglobulin ( Ig ) gene</dna> , to which <protein>NF-kappa B</protein> binding was also decreased by FK506 , indicating that both <dna>IL-8 kappa B-like site</dna> and Ig <dna>kappa B site</dna> are FK506-sensitive in spite of the difference of <protein>binding factors</protein> ."}439{"id": "438", "text": "Our results indicate that not only the reported IL-2 NF-AT and NFIL-2A sites and Ig kappa B site , but also the IL-8 AP-1 and kappa B-like sites are terminals of FK506-sensitive pathway involving Ca2+ mobilization .", "annotated_text": "Our results indicate that not only the reported <dna>IL-2 NF-AT and NFIL-2A sites</dna> and Ig <dna>kappa B site</dna> , but also the <protein>IL-8</protein> <dna>AP-1</dna> and <dna>kappa B-like sites</dna> are terminals of FK506-sensitive pathway involving Ca2+ mobilization ."}440{"id": "439", "text": "Androgen binding sites in peripheral human mononuclear leukocytes of healthy males and females .", "annotated_text": "<protein>Androgen binding sites</protein> in <cell_type>peripheral human mononuclear leukocytes</cell_type> of healthy males and females ."}441{"id": "440", "text": "Androgen binding sites have been identified in circulating human mononuclear leukocytes of healthy donors of both sexes .", "annotated_text": "<protein>Androgen binding sites</protein> have been identified in <cell_type>circulating human mononuclear leukocytes</cell_type> of healthy donors of both sexes ."}442{"id": "441", "text": "Cells were separated from blood samples on a Ficoll gradient and incubated with different concentrations of [ 3H ] testosterone in the presence or absence of a 400-fold excess of unlabelled testosterone .", "annotated_text": "Cells were separated from blood samples on a Ficoll gradient and incubated with different concentrations of [ 3H ] testosterone in the presence or absence of a 400-fold excess of unlabelled testosterone ."}443{"id": "442", "text": "Binding data were derived from Scatchard analysis .", "annotated_text": "Binding data were derived from Scatchard analysis ."}444{"id": "443", "text": "The binding sites fulfil the required criteria for specific steroid binding sites however differ somewhat from the classic androgen receptors from genital skin fibroblast : in fertile adult males ( n = 20 ) the binding sites showed ( 1 ) a high affinity for testosterone ( 1.32 +/- 0.49 nM ; mean +/- SD ) , ( 2 ) a saturable capacity ( 184 +/- 52 binding sites per cell ; mean +/- SD ) , and ( 3 ) a characteristic competitive binding profile for other steroid hormones ( relative binding affinities : testosterone = dihydrotestosterone > 17 beta-estradiol > progesterone , whereas aldosterone , 17-hydroxy-progesterone and cortisol did not compete appreciably ) .", "annotated_text": "The <protein>binding sites</protein> fulfil the required criteria for specific <protein>steroid binding sites</protein> however differ somewhat from the classic <protein>androgen receptors</protein> from <cell_type>genital skin fibroblast</cell_type> : in fertile adult males ( n = 20 ) the <protein>binding sites</protein> showed ( 1 ) a high affinity for testosterone ( 1.32 +/- 0.49 nM ; mean +/- SD ) , ( 2 ) a saturable capacity ( 184 +/- 52 <protein>binding sites</protein> per cell ; mean +/- SD ) , and ( 3 ) a characteristic competitive binding profile for other steroid hormones ( relative binding affinities : testosterone = dihydrotestosterone > 17 beta-estradiol > progesterone , whereas aldosterone , 17-hydroxy-progesterone and cortisol did not compete appreciably ) ."}445{"id": "444", "text": "Furthermore the number of binding sites determined using [ 3H ] dihydrotestosterone , [ 3H ] RU-1881 , or [ 3H ] testosterone were comparable .", "annotated_text": "Furthermore the number of <protein>binding sites</protein> determined using [ 3H ] dihydrotestosterone , [ 3H ] RU-1881 , or [ 3H ] testosterone were comparable ."}446{"id": "445", "text": "This raises the possibility that androgen receptors in peripheral mononuclear leukocytes differ from those in genital skin fibroblasts .", "annotated_text": "This raises the possibility that <protein>androgen receptors</protein> in <cell_type>peripheral mononuclear leukocytes</cell_type> differ from those in <cell_type>genital skin fibroblasts</cell_type> ."}447{"id": "446", "text": "There was no apparent correlation between serum testosterone concentrations and androgen binding sites .", "annotated_text": "There was no apparent correlation between serum testosterone concentrations and <protein>androgen binding sites</protein> ."}448{"id": "447", "text": "In fertile women remarkable changes in androgen binding sites were seen in the course of the menstrual cycle , with a significant increase in the immediate preovulatory period .", "annotated_text": "In fertile women remarkable changes in <protein>androgen binding sites</protein> were seen in the course of the menstrual cycle , with a significant increase in the immediate preovulatory period ."}449{"id": "448", "text": "The presence of androgen receptors in peripheral mononuclear leukocytes provides for the first time the experimental basis for an hypothesis of direct , receptor-mediated effects of androgens on mature immunocompetent cells .", "annotated_text": "The presence of <protein>androgen receptors</protein> in <cell_type>peripheral mononuclear leukocytes</cell_type> provides for the first time the experimental basis for an hypothesis of direct , receptor-mediated effects of androgens on <cell_type>mature immunocompetent cells</cell_type> ."}450{"id": "449", "text": "The immunological implications of these results are discussed .", "annotated_text": "The immunological implications of these results are discussed ."}451{"id": "450", "text": "Induction of IL-8 expression in T cells uses the CD28 costimulatory pathway .", "annotated_text": "Induction of <protein>IL-8</protein> expression in <cell_type>T cells</cell_type> uses the <protein>CD28</protein> costimulatory pathway ."}452{"id": "451", "text": "IL-8 , a potent chemotactic factor for neutrophil granulocytes and lymphocytes , is a proinflammatory cytokine secreted by a variety of cell types , including T cells .", "annotated_text": "<protein>IL-8</protein> , a potent <protein>chemotactic factor</protein> for <cell_type>neutrophil granulocytes</cell_type> and <cell_type>lymphocytes</cell_type> , is a proinflammatory cytokine secreted by a variety of cell types , including <cell_type>T cells</cell_type> ."}453{"id": "452", "text": "Stimulation of the CD28 cell surface molecule delivers costimulatory signals essential for lymphokine production in activated T cells via a conserved sequence element found in the promoter of several lymphokine genes .", "annotated_text": "Stimulation of the <protein>CD28 cell surface molecule</protein> delivers costimulatory signals essential for <protein>lymphokine</protein> production in <cell_type>activated T cells</cell_type> via a <dna>conserved sequence element</dna> found in the <dna>promoter</dna> of several <dna>lymphokine genes</dna> ."}454{"id": "453", "text": "Anti-CD28-stimulated T cells produced significant amounts of IL-8 ; additionally , costimulation with anti-CD3 and anti-CD28 Abs resulted in a synergistic induction of IL-8 secretion .", "annotated_text": "<cell_line>Anti-CD28-stimulated T cells</cell_line> produced significant amounts of <protein>IL-8</protein> ; additionally , costimulation with <protein>anti-CD3</protein> and <protein>anti-CD28 Abs</protein> resulted in a synergistic induction of <protein>IL-8</protein> secretion ."}455{"id": "454", "text": "Sequence homology , single nucleotide mutations , and anti-CD28 Ab stimulation studies established that the NF-kappa B-like sequence in the promoter of the IL-8 gene functioned as a CD28 response element .", "annotated_text": "Sequence homology , single nucleotide mutations , and <protein>anti-CD28 Ab</protein> stimulation studies established that the <dna>NF-kappa B-like sequence</dna> in the <dna>promoter</dna> of the <dna>IL-8 gene</dna> functioned as a <dna>CD28 response element</dna> ."}456{"id": "455", "text": "Furthermore , cyclosporin A , but not rapamycin , blocked the synergistic induction of IL-8 expression achieved with anti-CD3 and anti- CD28 costimulation .", "annotated_text": "Furthermore , cyclosporin A , but not rapamycin , blocked the synergistic induction of <protein>IL-8</protein> expression achieved with <protein>anti-CD3</protein> and anti- <protein>CD28</protein> costimulation ."}457{"id": "456", "text": "The involvement of a CD28 response element in the induction of IL-8 expression in activated T cells may provide new insights into the pathogenesis and persistence of immune disorders characterized by increased levels of IL-8 , such as psoriasis and rheumatoid arthritis .", "annotated_text": "The involvement of a <dna>CD28 response element</dna> in the induction of <protein>IL-8</protein> expression in <cell_type>activated T cells</cell_type> may provide new insights into the pathogenesis and persistence of immune disorders characterized by increased levels of <protein>IL-8</protein> , such as psoriasis and rheumatoid arthritis ."}458{"id": "457", "text": "MHC class II signaling in B-cell activation [ see comments ]", "annotated_text": "<protein>MHC class II</protein> signaling in <cell_type>B-cell</cell_type> activation [ see comments ]"}459{"id": "458", "text": "The cognate interaction between T cells and antigen-presenting cells ( APCs ) , mediated by major histocompatibility complex ( MHC ) class II molecules , results in the delivery of activation signals to the APC .", "annotated_text": "The cognate interaction between <cell_type>T cells</cell_type> and <cell_type>antigen-presenting cells</cell_type> ( <cell_type>APCs</cell_type> ) , mediated by <protein>major histocompatibility complex ( MHC ) class II molecules</protein> , results in the delivery of activation signals to the <cell_type>APC</cell_type> ."}460{"id": "459", "text": "These signals contribute to the expression of co-stimulatory activity by APCs and have important consequences for cell effector function .", "annotated_text": "These signals contribute to the expression of co-stimulatory activity by <cell_type>APCs</cell_type> and have important consequences for cell effector function ."}461{"id": "460", "text": "MHC class II molecules also serve as receptors for B-cell stimulation by microbial superantigens .", "annotated_text": "<protein>MHC class II</protein> molecules also serve as receptors for <cell_type>B-cell</cell_type> stimulation by <protein>microbial superantigens</protein> ."}462{"id": "461", "text": "In this review , Paul Scholl and Raif Geha discuss recent advances in our understanding of mechanisms of MHC class II signaling and analyse their role in human B-cell activation .", "annotated_text": "In this review , Paul Scholl and Raif Geha discuss recent advances in our understanding of mechanisms of <protein>MHC class II</protein> signaling and analyse their role in human <cell_type>B-cell</cell_type> activation ."}463{"id": "462", "text": "Effects of glucocorticoids in rheumatoid arthritis .", "annotated_text": "Effects of glucocorticoids in rheumatoid arthritis ."}464{"id": "463", "text": "Diminished glucocorticoid receptors do not result in glucocorticoid resistance .", "annotated_text": "Diminished <protein>glucocorticoid receptors</protein> do not result in glucocorticoid resistance ."}465{"id": "464", "text": "OBJECTIVE .", "annotated_text": "OBJECTIVE ."}466{"id": "465", "text": "Lymphocytes of patients with rheumatoid arthritis ( RA ) have diminished receptor density ; thus , patients with RA should show partial resistance to glucocorticoids .", "annotated_text": "Lymphocytes of patients with rheumatoid arthritis ( RA ) have diminished receptor density ; thus , patients with RA should show partial resistance to glucocorticoids ."}467{"id": "466", "text": "We investigated the glucocorticoid sensitivity of lymphocytes in RA patients compared with healthy subjects .", "annotated_text": "We investigated the glucocorticoid sensitivity of <cell_type>lymphocytes</cell_type> in RA patients compared with healthy subjects ."}468{"id": "467", "text": "METHODS .", "annotated_text": "METHODS ."}469{"id": "468", "text": "We determined the effects of glucocorticoids on lymphocyte proliferation and cytokine release .", "annotated_text": "We determined the effects of glucocorticoids on <cell_type>lymphocyte</cell_type> proliferation and <protein>cytokine</protein> release ."}470{"id": "469", "text": "RESULTS .", "annotated_text": "RESULTS ."}471{"id": "470", "text": "Proliferation and cytokine release were inhibited in RA patients to the same extent as in healthy controls .", "annotated_text": "Proliferation and <protein>cytokine</protein> release were inhibited in RA patients to the same extent as in healthy controls ."}472{"id": "471", "text": "CONCLUSION .", "annotated_text": "CONCLUSION ."}473{"id": "472", "text": "Diminished receptor density in RA patients does not result in glucocorticoid resistance .", "annotated_text": "Diminished receptor density in RA patients does not result in glucocorticoid resistance ."}474{"id": "473", "text": "Arrested development : understanding v-abl .", "annotated_text": "Arrested development : understanding <dna>v-abl</dna> ."}475{"id": "474", "text": "The protein tyrosine kinase activity of the v-abl oncogene has been demonstrated to subvert the normal second messenger systems used by lymphoid cells for growth and differentiation .", "annotated_text": "The <protein>protein tyrosine kinase</protein> activity of the <dna>v-abl oncogene</dna> has been demonstrated to subvert the normal second messenger systems used by <cell_type>lymphoid cells</cell_type> for growth and differentiation ."}476{"id": "475", "text": "Transformation of bone marrow with the Abelson murine leukemia virus results in the appearance of B cell lineage cells arrested at the pre-B cell stage .", "annotated_text": "Transformation of bone marrow with the Abelson murine leukemia virus results in the appearance of <cell_type>B cell lineage cells</cell_type> arrested at the pre-B cell stage ."}477{"id": "476", "text": "Recent reports have characterized these cells expressing high v-abl kinase activity as deficient in detectable NF-kappaB DNA binding activity and low level RAG gene expression .", "annotated_text": "Recent reports have characterized these cells expressing high <dna>v-abl</dna> kinase activity as deficient in detectable <protein>NF-kappaB</protein> DNA binding activity and low level <dna>RAG gene</dna> expression ."}478{"id": "477", "text": "These observations suggest that v-abl may be inhibiting the differentiation of B cells by blocking these two crucial elements in the maturation pathway .", "annotated_text": "These observations suggest that <dna>v-abl</dna> may be inhibiting the differentiation of <cell_type>B cells</cell_type> by blocking these two crucial elements in the maturation pathway ."}479{"id": "478", "text": "Corticosteroid receptors in lymphocytes : a possible marker of brain involution ?", "annotated_text": "<protein>Corticosteroid receptors</protein> in <cell_type>lymphocytes</cell_type> : a possible marker of brain involution ?"}480{"id": "479", "text": "A similarity has recently been found between the regulation of corticosteroid receptors in brain and in lymphoid tissue .", "annotated_text": "A similarity has recently been found between the regulation of <protein>corticosteroid receptors</protein> in brain and in lymphoid tissue ."}481{"id": "480", "text": "We have studied the regulation of corticosteroid receptors in human mononuclear leukocytes as a possible marker of brain involution .", "annotated_text": "We have studied the regulation of <protein>corticosteroid receptors</protein> in <cell_type>human mononuclear leukocytes</cell_type> as a possible marker of brain involution ."}482{"id": "481", "text": "Type I corticosteroid receptors are down regulated by excess of mineralocorticoids ( primary and secondary hyperaldosteronism , pseudohyperaldosteronism ) and of glucocorticoids ( Cushing 's syndrome ) . Type II corticosteroid receptors are not reduced by excess of endogenous corticosteroids ( Cushing 's syndrome ) .", "annotated_text": "<protein>Type I corticosteroid receptors</protein> are down regulated by excess of mineralocorticoids ( primary and secondary hyperaldosteronism , pseudohyperaldosteronism ) and of glucocorticoids ( Cushing 's syndrome ) . <protein>Type II corticosteroid receptors</protein> are not reduced by excess of endogenous corticosteroids ( Cushing 's syndrome ) ."}483{"id": "482", "text": "In normal adults there is a direct significant correlation between plasma cortisol and Type I and between plasma cortisol and Type II receptors in mononuclear leukocytes , while in Cushing 's syndrome the correlation is inverse between plasma cortisol at 8 a.m. and Type II receptors .", "annotated_text": "In normal adults there is a direct significant correlation between plasma cortisol and <protein>Type I</protein> and between plasma cortisol and <protein>Type II receptors</protein> in <cell_type>mononuclear leukocytes</cell_type> , while in Cushing 's syndrome the correlation is inverse between plasma cortisol at 8 a.m. and <protein>Type II receptors</protein> ."}484{"id": "483", "text": "In an aged population the mean numbers of Type I and of Type II receptors are lower and plasma cortisol is higher than in adult controls , but the increase of plasma cortisol is not followed by a clinical picture of hypercorticism .", "annotated_text": "In an aged population the mean numbers of <protein>Type I</protein> and of <protein>Type II receptors</protein> are lower and plasma cortisol is higher than in adult controls , but the increase of plasma cortisol is not followed by a clinical picture of hypercorticism ."}485{"id": "484", "text": "Corticosteroid Type I and Type II receptors are inversely correlated with age .", "annotated_text": "<protein>Corticosteroid Type I and Type II receptors</protein> are inversely correlated with age ."}486{"id": "485", "text": "After dexamethasone suppression ( 1 mg at 11 p.m. ) Type I receptors always decrease in controls while the response of Type II is not homogeneous .", "annotated_text": "After dexamethasone suppression ( 1 mg at 11 p.m. ) <protein>Type I receptors</protein> always decrease in controls while the response of <protein>Type II</protein> is not homogeneous ."}487{"id": "486", "text": "In an aged group of patients , both receptors are reduced by dexamethasone .", "annotated_text": "In an aged group of patients , both receptors are reduced by dexamethasone ."}488{"id": "487", "text": "We conclude that the decrease with age of corticosteroid receptors is possibly related to a physiological involution of corticosteroid receptors and that this reduction does increase plasma cortisol concentration , without affecting the glucocorticoid effector mechanism .", "annotated_text": "We conclude that the decrease with age of <protein>corticosteroid receptors</protein> is possibly related to a physiological involution of <protein>corticosteroid receptors</protein> and that this reduction does increase plasma cortisol concentration , without affecting the glucocorticoid effector mechanism ."}489{"id": "488", "text": "All-trans retinoic acid and 1 alpha , 25-dihydroxyvitamin D3 co-operate to promote differentiation of the human promyeloid leukemia cell line HL60 to monocytes .", "annotated_text": "All-trans retinoic acid and 1 alpha , 25-dihydroxyvitamin D3 co-operate to promote differentiation of the <cell_line>human promyeloid leukemia cell line</cell_line> <cell_line>HL60</cell_line> to <cell_type>monocytes</cell_type> ."}490{"id": "489", "text": "A basis for differentiation therapy of leukemias is provided by knowledge of agents which induce specific lineage maturation .", "annotated_text": "A basis for differentiation therapy of leukemias is provided by knowledge of agents which induce specific lineage maturation ."}491{"id": "490", "text": "All-trans retinoic acid ( RA ) induces differentiation of HL60 cells to neutrophils and is used to treat acute promyelocytic leukemia .", "annotated_text": "All-trans retinoic acid ( RA ) induces differentiation of <cell_line>HL60 cells</cell_line> to <cell_type>neutrophils</cell_type> and is used to treat acute promyelocytic leukemia ."}492{"id": "491", "text": "We observed that RA did not induced neutrophil differentiation in serum-free grown HL60 cells whereas 50 nM 1 alpha , 25-dihydroxyvitamin D3 ( D3 ) induced maximal monocyte differentiation .", "annotated_text": "We observed that RA did not induced neutrophil differentiation in <cell_line>serum-free grown HL60 cells</cell_line> whereas 50 nM 1 alpha , 25-dihydroxyvitamin D3 ( D3 ) induced maximal monocyte differentiation ."}493{"id": "492", "text": "Increasing RA concentrations reduced the D3 concentration required for monocyte differentiation .", "annotated_text": "Increasing RA concentrations reduced the D3 concentration required for monocyte differentiation ."}494{"id": "493", "text": "Cells treated with 5 nM D3 showed little response , but differentiated maximally with 5 nM D3 and 10 nM RA .", "annotated_text": "Cells treated with 5 nM D3 showed little response , but differentiated maximally with 5 nM D3 and 10 nM RA ."}495{"id": "494", "text": "The D3 analogs MC903 , EB1089 and KH1060 were more potent inducers of monocyte differentiation .", "annotated_text": "The D3 analogs MC903 , EB1089 and KH1060 were more potent inducers of monocyte differentiation ."}496{"id": "495", "text": "The extent to which analog activity was increased after cotreatment with RA was inversely related to potency .", "annotated_text": "The extent to which analog activity was increased after cotreatment with RA was inversely related to potency ."}497{"id": "496", "text": "Twenty-four hour treatment with 10 nM RA primed cells for response to 5 nM D3 ; the reverse sequence being ineffective .", "annotated_text": "Twenty-four hour treatment with 10 nM <cell_line>RA primed cells</cell_line> for response to 5 nM D3 ; the reverse sequence being ineffective ."}498{"id": "497", "text": "Priming with 10 nM RA , or subsequent treatment with D3 ( 5 nM ) , did not alter expression of mRNAs encoding receptors for D3 ( VDR ) , RA ( RAR alpha ) or 9-CIS RA ( RXR alpha , beta , gamma ) .", "annotated_text": "Priming with 10 nM RA , or subsequent treatment with D3 ( 5 nM ) , did not alter expression of <rna>mRNAs</rna> encoding <protein>receptors</protein> for D3 ( <protein>VDR</protein> ) , RA ( <protein>RAR alpha</protein> ) or 9-CIS RA ( <protein>RXR alpha , beta , gamma</protein> ) ."}499{"id": "498", "text": "That RA promotes both neutrophil and monocyte differentiation has implications for the use of RA and D3 in treatment of leukemias and provides insight into mechanisms whereby RAR , VDR and RXR facilitate monocyte differentiation .", "annotated_text": "That RA promotes both neutrophil and monocyte differentiation has implications for the use of RA and D3 in treatment of leukemias and provides insight into mechanisms whereby RAR , <protein>VDR</protein> and <protein>RXR</protein> facilitate monocyte differentiation ."}500{"id": "499", "text": "[ An overexpression of retinoic acid receptor alpha blocks myeloid cell differentiation at the promyelocyte stage ]", "annotated_text": "[ An overexpression of <protein>retinoic acid receptor alpha</protein> blocks <cell_type>myeloid cell</cell_type> differentiation at the promyelocyte stage ]"}501{"id": "500", "text": "Retinoic acid ( RA ) , a vitamin A derivative , exerts a wide range of biological effects related to cell proliferation and differentiation .", "annotated_text": "Retinoic acid ( RA ) , a vitamin A derivative , exerts a wide range of biological effects related to cell proliferation and differentiation ."}502{"id": "501", "text": "The pleiotropic effects of RA are thought to be mediated through specific nuclear RA receptors ( RARs ) .", "annotated_text": "The pleiotropic effects of RA are thought to be mediated through specific nuclear <protein>RA receptors</protein> ( <protein>RARs</protein> ) ."}503{"id": "502", "text": "RARs are members of the steroid/thyroid hormone receptor superfamily and exhibit a molecular structure that possess discrete DNA-binding and RA ( ligand ) -binding domains .", "annotated_text": "<protein>RARs</protein> are members of the <protein>steroid/thyroid hormone receptor superfamily</protein> and exhibit a molecular structure that possess discrete DNA-binding and <protein>RA ( ligand ) -binding domains</protein> ."}504{"id": "503", "text": "In hematopoietic system , RA and RARs , predominantly RAR alpha may play key roles for the proliferation and differentiation of hematopoietic progenitors .", "annotated_text": "In hematopoietic system , RA and <protein>RARs</protein> , predominantly <protein>RAR alpha</protein> may play key roles for the proliferation and differentiation of <cell_type>hematopoietic progenitors</cell_type> ."}505{"id": "504", "text": "However , it is currently unknown how RA and RARs are involved in regulating normal hematopoietic differentiation .", "annotated_text": "However , it is currently unknown how RA and <protein>RARs</protein> are involved in regulating normal hematopoietic differentiation ."}506{"id": "505", "text": "To make clear the roles of RA and RAR alpha in the normal hematopoiesis , I have introduced the construct of human RAR alpha ( hRAR alpha ) into murine bone marrow cells with retroviral vector , and selected infected cells with drug resistant marker ( Neo ( r ) ) cultured on the stroma cell line ( PA6-neo ) , and analyzed the behavior of infected cells .", "annotated_text": "To make clear the roles of RA and <protein>RAR alpha</protein> in the normal hematopoiesis , I have introduced the construct of <protein>human RAR alpha</protein> ( <protein>hRAR alpha</protein> ) into <cell_type>murine bone marrow cells</cell_type> with retroviral vector , and selected infected cells with <dna>drug resistant marker</dna> ( <dna>Neo ( r )</dna> ) cultured on the <cell_line>stroma cell line</cell_line> ( <cell_line>PA6-neo</cell_line> ) , and analyzed the behavior of <cell_type>infected cells</cell_type> ."}507{"id": "506", "text": "All of procedure were done in vitro .", "annotated_text": "All of procedure were done in vitro ."}508{"id": "507", "text": "Most cells infected with hRAR alpha exhibited promyelocytic morphology and were thought to be blocked at the promyelocytic stage in their myeloid differentiation .", "annotated_text": "Most cells infected with <protein>hRAR alpha</protein> exhibited <cell_type>promyelocytic morphology</cell_type> and were thought to be blocked at the promyelocytic stage in their myeloid differentiation ."}509{"id": "508", "text": "Furthermore , these immature cells differentiated terminally into mature granulocytes by adding with RA ( 10 ( -6 ) M ) .", "annotated_text": "Furthermore , these <cell_type>immature cells</cell_type> differentiated terminally into mature granulocytes by adding with RA ( 10 ( -6 ) M ) ."}510{"id": "509", "text": "RAR alpha infected cells were also able to differentiate into mature macrophages in the both of long term culture and IL3 colony .", "annotated_text": "<protein>RAR alpha</protein> <cell_type>infected cells</cell_type> were also able to differentiate into <cell_type>mature macrophages</cell_type> in the both of long term culture and <cell_line>IL3 colony</cell_line> ."}511{"id": "510", "text": "These observations suggest that an overexpression of RAR alpha alone is effective to suppress myeloid cell differentiation and RAR alpha plays a crucial role in the terminal differentiation of myeloid precursors .", "annotated_text": "These observations suggest that an overexpression of <protein>RAR alpha</protein> alone is effective to suppress <cell_type>myeloid cell</cell_type> differentiation and <protein>RAR alpha</protein> plays a crucial role in the terminal differentiation of myeloid precursors ."}512{"id": "511", "text": "The system described here may serve as a model for studying the the essential genes for differentiation of normal bone marrow cells .", "annotated_text": "The system described here may serve as a model for studying the the <dna>essential genes</dna> for differentiation of <cell_type>normal bone marrow cells</cell_type> ."}513{"id": "512", "text": "Hypoxic induction of interleukin-8 gene expression in human endothelial cells .", "annotated_text": "Hypoxic induction of <dna>interleukin-8 gene</dna> expression in <cell_type>human endothelial cells</cell_type> ."}514{"id": "513", "text": "Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion , we have sought mechanisms by which PMNs are directed into hypoxic tissue .", "annotated_text": "Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion , we have sought mechanisms by which <cell_type>PMNs</cell_type> are directed into hypoxic tissue ."}515{"id": "514", "text": "Incubation of human endothelial cells ( ECs ) in hypoxia , PO2 approximately 14-18 Torr , led to time-dependent release of IL-8 antigen into the conditioned medium ; this was accompanied by increased chemotactic activity for PMNs , blocked by antibody to IL-8 .", "annotated_text": "Incubation of <cell_type>human endothelial cells</cell_type> ( <cell_type>ECs</cell_type> ) in hypoxia , PO2 approximately 14-18 Torr , led to time-dependent release of <protein>IL-8</protein> antigen into the conditioned medium ; this was accompanied by increased chemotactic activity for <cell_type>PMNs</cell_type> , blocked by antibody to <protein>IL-8</protein> ."}516{"id": "515", "text": "Production of IL-8 by hypoxic ECs occurred concomitantly with both increased levels of IL-8 mRNA , based on polymerase chain reaction analysis , and increased IL-8 transcription , based on nuclear run-on assays .", "annotated_text": "Production of <protein>IL-8</protein> by hypoxic <cell_type>ECs</cell_type> occurred concomitantly with both increased levels of <rna>IL-8 mRNA</rna> , based on polymerase chain reaction analysis , and increased <protein>IL-8</protein> transcription , based on nuclear run-on assays ."}517{"id": "516", "text": "Northern analysis of mRNA from hypoxic ECs also demonstrated increased levels of mRNA for macrophage chemotactic protein-1 , another member of the chemokine superfamily of proinflammatory cytokines .", "annotated_text": "Northern analysis of mRNA from hypoxic <cell_type>ECs</cell_type> also demonstrated increased levels of <rna>mRNA</rna> for <protein>macrophage chemotactic protein-1</protein> , another member of the <protein>chemokine superfamily</protein> of <protein>proinflammatory cytokines</protein> ."}518{"id": "517", "text": "IL-8 gene induction was associated with the presence of increased binding activity in nuclear extracts from hypoxic ECs for the NF-kB site .", "annotated_text": "<dna>IL-8 gene</dna> induction was associated with the presence of increased binding activity in nuclear extracts from <cell_type>hypoxic ECs</cell_type> for the NF-kB site ."}519{"id": "518", "text": "Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of IL-8 antigen compared with normoxic controls .", "annotated_text": "Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of <protein>IL-8 antigen</protein> compared with normoxic controls ."}520{"id": "519", "text": "In mice exposed to hypoxia ( PO2 approximately 30-40 Torr ) , there was increased pulmonary leukostasis , as evidenced by increased myeloperoxidase activity in tissue homogenates .", "annotated_text": "In mice exposed to hypoxia ( PO2 approximately 30-40 Torr ) , there was increased pulmonary leukostasis , as evidenced by increased <protein>myeloperoxidase</protein> activity in tissue homogenates ."}521{"id": "520", "text": "In parallel , increased levels of transcripts for IP-10 , a murine homologue in the chemokine family related to IL-8 , were observed in hypoxic lung tissue .", "annotated_text": "In parallel , increased levels of transcripts for <protein>IP-10</protein> , a murine homologue in the <protein>chemokine family</protein> related to <protein>IL-8</protein> , were observed in hypoxic lung tissue ."}522{"id": "521", "text": "Taken together , these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis .", "annotated_text": "Taken together , these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis ."}523{"id": "522", "text": "Thrombin and thrombin receptor agonist peptide induce early events of T cell activation and synergize with TCR cross-linking for CD69 expression and interleukin 2 production .", "annotated_text": "<protein>Thrombin</protein> and <protein>thrombin receptor</protein> agonist peptide induce early events of T cell activation and synergize with <protein>TCR</protein> cross-linking for <protein>CD69</protein> expression and interleukin 2 production ."}524{"id": "523", "text": "Thrombin stimulation of the T leukemic cell line Jurkat induced a transient increase in [ Ca2+ ] i .", "annotated_text": "<protein>Thrombin</protein> stimulation of the <cell_line>T leukemic cell line Jurkat</cell_line> induced a transient increase in [ Ca2+ ] i ."}525{"id": "524", "text": "Proteolytic activity of the enzyme was required for this effect since diisopropyl fluorophosphate-thrombin failed to increase [ Ca2+ ] i .", "annotated_text": "Proteolytic activity of the <protein>enzyme</protein> was required for this effect since <protein>diisopropyl fluorophosphate-thrombin</protein> failed to increase [ Ca2+ ] i ."}526{"id": "525", "text": "Furthermore , hirudin and anti-thrombin III inhibited the thrombin-induced [ Ca2+ ] i rise in Jurkat T cells .", "annotated_text": "Furthermore , hirudin and <protein>anti-thrombin III</protein> inhibited the thrombin-induced [ Ca2+ ] i rise in <cell_line>Jurkat T cells</cell_line> ."}527{"id": "526", "text": "A synthetic thrombin receptor agonist peptide ( TRP ) of 7 residues ( SFLLRNP ) was found to be as effective as thrombin for [ Ca2+ ] i mobilization , and both agonists induced Ca2+ release exclusively from internal stores .", "annotated_text": "A synthetic <protein>thrombin receptor</protein> agonist peptide ( TRP ) of 7 residues ( SFLLRNP ) was found to be as effective as <protein>thrombin</protein> for [ Ca2+ ] i mobilization , and both agonists induced Ca2+ release exclusively from internal stores ."}528{"id": "527", "text": "Thrombin stimulated tyrosine phosphorylation of several proteins of molecular mass 40 , 42 , 70 , 120 , and 130 kDa .", "annotated_text": "<protein>Thrombin</protein> stimulated tyrosine phosphorylation of several proteins of <protein>molecular mass 40 , 42 , 70 , 120 , and 130 kDa</protein> ."}529{"id": "528", "text": "There was a good correlation between thrombin -induced tyrosine phosphorylation of the latter three proteins and Ca2+ mobilization .", "annotated_text": "There was a good correlation between <protein>thrombin</protein> -induced tyrosine phosphorylation of the latter three proteins and Ca2+ mobilization ."}530{"id": "529", "text": "Thrombin and TRP also caused translocation of protein kinase C from the cytosol to the plasma membrane .", "annotated_text": "<protein>Thrombin</protein> and TRP also caused translocation of <protein>protein kinase C</protein> from the cytosol to the plasma membrane ."}531{"id": "530", "text": "As a likely consequence of these events , thrombin activated the nuclear factor NF-kB .", "annotated_text": "As a likely consequence of these events , <protein>thrombin</protein> activated the <protein>nuclear factor NF-kB</protein> ."}532{"id": "531", "text": "Several cell lines of hematopoietic origin including the leukemic T cell line HPB.ALL and the erythroleukemic cell line K562 were responsive to thrombin , whereas others such as THP1 , a myelomonocytic cell line , and BL2 , a Burkitt lymphoma were refractory to thrombin or TRP stimulation .", "annotated_text": "Several cell lines of hematopoietic origin including the <cell_line>leukemic T cell line HPB.ALL</cell_line> and the <cell_line>erythroleukemic cell line K562</cell_line> were responsive to <protein>thrombin</protein> , whereas others such as <cell_line>THP1</cell_line> , a <cell_line>myelomonocytic cell line</cell_line> , and <cell_line>BL2 ,</cell_line> a <cell_line>Burkitt lymphoma</cell_line> were refractory to <protein>thrombin</protein> or TRP stimulation ."}533{"id": "532", "text": "The magnitude of the thrombin response in the different cell types paralleled the expression of the thrombin receptor mRNA .", "annotated_text": "The magnitude of the <protein>thrombin</protein> response in the different cell types paralleled the expression of the <rna>thrombin receptor mRNA</rna> ."}534{"id": "533", "text": "We found that activation of Jurkat T cells by a combination of phytohemagglutinin and phorbol 12-myristate 13-acetate led to a dramatic inhibition of thrombin receptor mRNA expression and to a concomitant loss of the thrombin response .", "annotated_text": "We found that activation of <cell_line>Jurkat T cells</cell_line> by a combination of <protein>phytohemagglutinin</protein> and phorbol 12-myristate 13-acetate led to a dramatic inhibition of <rna>thrombin receptor mRNA</rna> expression and to a concomitant loss of the <protein>thrombin</protein> response ."}535{"id": "534", "text": "Finally , we demonstrate that thrombin and TRP enhanced CD69 expression and interleukin 2 production induced by T cell receptor cross-linking in both Jurkat T cells and peripheral blood lymphocytes .", "annotated_text": "Finally , we demonstrate that <protein>thrombin</protein> and TRP enhanced <protein>CD69</protein> expression and <protein>interleukin 2</protein> production induced by <protein>T cell receptor</protein> cross-linking in both <cell_line>Jurkat T cells</cell_line> and peripheral blood <cell_type>lymphocytes</cell_type> ."}536{"id": "535", "text": "These findings highlight the role of thrombin as a potential regulator of T lymphocyte activation .", "annotated_text": "These findings highlight the role of <protein>thrombin</protein> as a potential regulator of <cell_type>T lymphocyte</cell_type> activation ."}537{"id": "536", "text": "Stress response of senescent T lymphocytes : reduced hsp70 is independent of the proliferative block .", "annotated_text": "Stress response of <cell_type>senescent T lymphocytes</cell_type> : reduced <protein>hsp70</protein> is independent of the proliferative block ."}538{"id": "537", "text": "Senescent human T lymphocyte cultures are unable to undergo proliferation , but show no difference from early passage cells in cytotoxic function or surface antigenic profile .", "annotated_text": "<cell_line>Senescent human T lymphocyte cultures</cell_line> are unable to undergo proliferation , but show no difference from <cell_line>early passage cells</cell_line> in cytotoxic function or surface antigenic profile ."}539{"id": "538", "text": "A second feature of senescent T cells is the dramatic reduction in hsp70 production in response to heat shock .", "annotated_text": "A second feature of <cell_line>senescent T cells</cell_line> is the dramatic reduction in <protein>hsp70</protein> production in response to heat shock ."}540{"id": "539", "text": "This decline is associated with a decrease in binding of nuclear extracts to the consensus heat shock element .", "annotated_text": "This decline is associated with a decrease in binding of nuclear extracts to the <dna>consensus heat shock element</dna> ."}541{"id": "540", "text": "Interestingly , the progressive decline in the heat shock response of cultured T cells correlates with the percent proliferative life span completed rather than with the actual proliferative activity at the time of heat shock .", "annotated_text": "Interestingly , the progressive decline in the heat shock response of <cell_line>cultured T cells</cell_line> correlates with the percent proliferative life span completed rather than with the actual proliferative activity at the time of heat shock ."}542{"id": "541", "text": "This suggests that for senescent T cells the reduced ability to respond to heat shock by producing hsp70 , although possibly lying at the level of transcriptional control , may nevertheless be unrelated to the reduced DNA synthesis or the diminished proliferative activity also manifested by these cells .", "annotated_text": "This suggests that for <cell_type>senescent T cells</cell_type> the reduced ability to respond to heat shock by producing <protein>hsp70</protein> , although possibly lying at the level of transcriptional control , may nevertheless be unrelated to the reduced DNA synthesis or the diminished proliferative activity also manifested by these cells ."}543{"id": "542", "text": "Involvement of phospholipase D in the activation of transcription factor AP-1 in human T lymphoid Jurkat cells .", "annotated_text": "Involvement of <protein>phospholipase D</protein> in the activation of <protein>transcription factor AP-1</protein> in <cell_line>human T lymphoid Jurkat cells</cell_line> ."}544{"id": "543", "text": "The induction of the AP-1 transcription factor has been ascribed to the early events leading to T lymphocyte activation .", "annotated_text": "The induction of the <protein>AP-1</protein> <protein>transcription factor</protein> has been ascribed to the early events leading to T lymphocyte activation ."}545{"id": "544", "text": "We have examined the possibility that stimulation of phospholipase D ( PLD ) may regulate activation of transcription factor AP-1 in human T cells by transfecting human T lymphocyte Jurkat cells with a plasmid containing an AP-1 enhancer element and a chloramphenicol acetyltransferase reporter gene .", "annotated_text": "We have examined the possibility that stimulation of <protein>phospholipase D</protein> ( <protein>PLD</protein> ) may regulate activation of <protein>transcription factor AP-1</protein> in human T cells by transfecting human <cell_line>T lymphocyte Jurkat cells</cell_line> with a plasmid containing an <dna>AP-1 enhancer element</dna> and a <dna>chloramphenicol acetyltransferase reporter gene</dna> ."}546{"id": "545", "text": "We have detected activatable PLD in Jurkat cells , and we have found that addition of phosphatidic acid ( PA ) , the physiologic product of PLD action on phospholipids , is rapidly incorporated into Jurkat cells and leads to activation of transcription factor AP-1 .", "annotated_text": "We have detected activatable <protein>PLD</protein> in <cell_line>Jurkat cells</cell_line> , and we have found that addition of phosphatidic acid ( PA ) , the physiologic product of <protein>PLD</protein> action on phospholipids , is rapidly incorporated into <cell_line>Jurkat cells</cell_line> and leads to activation of <protein>transcription factor AP-1</protein> ."}547{"id": "546", "text": "Treatment of Jurkat cells with anti-CD3 mAb activated both PLD and transcription factor AP-1 .", "annotated_text": "Treatment of <cell_line>Jurkat cells</cell_line> with <protein>anti-CD3 mAb</protein> activated both <protein>PLD</protein> and <protein>transcription factor AP-1</protein> ."}548{"id": "547", "text": "Wortmannin , an inhibitor of receptor-coupled PLD activation , blocked the anti-CD3 -induced increases in both PLD activity and AP-1 enhancer activity .", "annotated_text": "Wortmannin , an inhibitor of receptor-coupled <protein>PLD</protein> activation , blocked the <protein>anti-CD3</protein> -induced increases in both <protein>PLD</protein> activity and <dna>AP-1 enhancer</dna> activity ."}549{"id": "548", "text": "We found a good correlation in the transfected cells between PLD activation and induction of AP-1 enhancer activity under different experimental conditions .", "annotated_text": "We found a good correlation in the <cell_line>transfected cells</cell_line> between <protein>PLD</protein> activation and induction of <dna>AP-1 enhancer</dna> activity under different experimental conditions ."}550{"id": "549", "text": "Furthermore , ethanol , an inhibitor of the PLD pathway , blocked the anti-CD3-stimulated AP-1 enhancer activity .", "annotated_text": "Furthermore , ethanol , an inhibitor of the <protein>PLD</protein> pathway , blocked the anti-CD3-stimulated <dna>AP-1 enhancer</dna> activity ."}551{"id": "550", "text": "However , this anti-CD3 -mediated response was not inhibited by neomycin , an inhibitor of phosphoinositide hydrolysis .", "annotated_text": "However , this <protein>anti-CD3</protein> -mediated response was not inhibited by neomycin , an inhibitor of phosphoinositide hydrolysis ."}552{"id": "551", "text": "The increases in AP-1 enhancer activity induced by PA or anti-CD3 mAb were efficiently abrogated by the presence of propranolol , an inhibitor of PA phosphohydrolase and protein kinase C ( PKC ) .", "annotated_text": "The increases in <dna>AP-1 enhancer</dna> activity induced by PA or <protein>anti-CD3 mAb</protein> were efficiently abrogated by the presence of propranolol , an inhibitor of PA <protein>phosphohydrolase</protein> and <protein>protein kinase C</protein> ( <protein>PKC</protein> ) ."}553{"id": "552", "text": "Furthermore , the PA -and the anti-CD3 -induced increases in AP-1 enhancer activity were blocked by the presence of PKC inhibitors or by PKC down-regulation .", "annotated_text": "Furthermore , the PA -and the <protein>anti-CD3</protein> -induced increases in <dna>AP-1 enhancer</dna> activity were blocked by the presence of <protein>PKC</protein> inhibitors or by <protein>PKC</protein> down-regulation ."}554{"id": "553", "text": "These data indicate that PLD stimulation can activate the transcription factor AP-1 in T lymphocytes , and suggest that the induction of AP-1 enhancer factor activity by PA is mediated via PKC stimulation , either through a direct activating effect of PA or through PA-derived diacylglycerol formation .", "annotated_text": "These data indicate that <protein>PLD</protein> stimulation can activate the <protein>transcription factor AP-1</protein> in <cell_type>T lymphocytes</cell_type> , and suggest that the induction of <dna>AP-1 enhancer</dna> factor activity by PA is mediated via <protein>PKC</protein> stimulation , either through a direct activating effect of PA or through PA-derived diacylglycerol formation ."}555{"id": "554", "text": "These data also provide evidence for a role of PLD -derived lipids in the induction of AP-1 enhancer activity resulting from stimulation of the TCR/CD3 complex , suggesting that increased PLD activity can play an important role in T lymphocyte activation .", "annotated_text": "These data also provide evidence for a role of <protein>PLD</protein> -derived lipids in the induction of <dna>AP-1 enhancer</dna> activity resulting from stimulation of the <protein>TCR/CD3 complex</protein> , suggesting that increased <protein>PLD</protein> activity can play an important role in <cell_type>T lymphocyte</cell_type> activation ."}556{"id": "555", "text": "Upregulation of bcl-2 by the Epstein-Barr virus latent membrane protein LMP1 : a B-cell-specific response that is delayed relative to NF-kappa B activation and to induction of cell surface markers .", "annotated_text": "Upregulation of <dna>bcl-2</dna> by the <protein>Epstein-Barr virus latent membrane protein</protein> <protein>LMP1</protein> : a B-cell-specific response that is delayed relative to <protein>NF-kappa B</protein> activation and to induction of <protein>cell surface markers</protein> ."}557{"id": "556", "text": "An ability of the Epstein-Barr virus latent membrane protein LMP1 to enhance the survival of infected B cells through upregulation of the bcl-2 oncogene was first suggested by experiments involving gene transfection and the selection of stable LMP1+ clones ( S.Henderson , M. Rowe , C.Gregory , F.Wang , E.Kieff , and A.Rickinson , Cell 65 : 1107-1115 , 1991 ) .", "annotated_text": "An ability of the <protein>Epstein-Barr virus latent membrane protein</protein> <protein>LMP1</protein> to enhance the survival of <cell_type>infected B cells</cell_type> through upregulation of the <dna>bcl-2 oncogene</dna> was first suggested by experiments involving gene transfection and the selection of stable <cell_line>LMP1+ clones</cell_line> ( S.Henderson , M. Rowe , C.Gregory , F.Wang , E.Kieff , and A.Rickinson , Cell 65 : 1107-1115 , 1991 ) ."}558{"id": "557", "text": "However , it was not possible to ascertain whether Bcl-2 upregulation was a specific consequence of LMP1 expression or an artifact of the selection procedure whereby rare Bcl-2+ cells already present in the starting population might best be able to tolerate the potentially toxic effects of LMP1 .", "annotated_text": "However , it was not possible to ascertain whether <protein>Bcl-2</protein> upregulation was a specific consequence of <protein>LMP1</protein> expression or an artifact of the selection procedure whereby rare <cell_line>Bcl-2+ cells</cell_line> already present in the starting population might best be able to tolerate the potentially toxic effects of <protein>LMP1</protein> ."}559{"id": "558", "text": "We therefore reexamined this issue by using two different experimental approaches that allowed LMP1 -induced effects to be monitored immediately following expression of the viral protein and in the absence of selective pressures ; activation of the NF-kappa B transcription factor and upregulation of the cell adhesion molecule ICAM-1 were used as early indices of LMP1 function .", "annotated_text": "We therefore reexamined this issue by using two different experimental approaches that allowed <protein>LMP1</protein> -induced effects to be monitored immediately following expression of the viral protein and in the absence of selective pressures ; activation of the <protein>NF-kappa B</protein> <protein>transcription factor</protein> and upregulation of the <protein>cell adhesion molecule</protein> <protein>ICAM-1</protein> were used as early indices of <protein>LMP1</protein> function ."}560{"id": "559", "text": "In the first approach , stable clones of two B-cell lines carrying an LMP1 gene under the control of an inducible metallothionein promoter were induced to express LMP1 in all cells .", "annotated_text": "In the first approach , stable clones of two <cell_line>B-cell lines</cell_line> carrying an <protein>LMP1</protein> gene under the control of an inducible <dna>metallothionein promoter</dna> were induced to express <protein>LMP1</protein> in all cells ."}561{"id": "560", "text": "Activation of NK-kappa B and upregulation of ICAM-1 occurred within 24 h and were followed at 48 to 72 h by upregulation of Bcl-2 .", "annotated_text": "Activation of <protein>NK-kappa B</protein> and upregulation of <protein>ICAM-1</protein> occurred within 24 h and were followed at 48 to 72 h by upregulation of <protein>Bcl-2</protein> ."}562{"id": "561", "text": "In the second approach , we tested the generality of this phenomenon by transiently expressing LMP1 from a strong constitutively active promoter in a range of different cell types .", "annotated_text": "In the second approach , we tested the generality of this phenomenon by transiently expressing <protein>LMP1</protein> from a strong constitutively active promoter in a range of different cell types ."}563{"id": "562", "text": "All six B-cell lines tested showed NF-kappa B activation in response to LMP1 expression , and this was followed in five of six lines by expression of ICAM-1 and Bcl-2 .", "annotated_text": "All six <cell_line>B-cell lines</cell_line> tested showed <protein>NF-kappa B</protein> activation in response to <protein>LMP1</protein> expression , and this was followed in five of six lines by expression of <protein>ICAM-1</protein> and <protein>Bcl-2</protein> ."}564{"id": "563", "text": "In the same experiments , all three non- B-cell lines showed NF-kappa B activation and ICAM-1 upregulation but never any effect upon Bcl-2 .", "annotated_text": "In the same experiments , all three non- <cell_line>B-cell lines</cell_line> showed <protein>NF-kappa B</protein> activation and <protein>ICAM-1</protein> upregulation but never any effect upon <protein>Bcl-2</protein> ."}565{"id": "564", "text": "We therefore conclude that Bcl-2 upregulation is part of the panoply of cellular changes induced by LMP1 but that the effect is cell type specific .", "annotated_text": "We therefore conclude that <protein>Bcl-2</protein> upregulation is part of the panoply of cellular changes induced by <protein>LMP1</protein> but that the effect is cell type specific ."}566{"id": "565", "text": "Our data also suggest that whilst NF-kappa B may be an essential component of LMP1 signal transduction , other cell-specific factors may be required to effect some functions of the viral protein .", "annotated_text": "Our data also suggest that whilst <protein>NF-kappa B</protein> may be an essential component of <protein>LMP1</protein> signal transduction , other <protein>cell-specific factors</protein> may be required to effect some functions of the <protein>viral protein</protein> ."}567{"id": "566", "text": "Long-term inositol phosphate release , but not tyrosine kinase activity , correlates with IL-2 secretion and NF-AT induction in anti-CD3-activated peripheral human T lymphocytes .", "annotated_text": "Long-term inositol phosphate release , but not <protein>tyrosine kinase</protein> activity , correlates with <protein>IL-2</protein> secretion and <protein>NF-AT</protein> induction in <cell_line>anti-CD3-activated peripheral human T lymphocytes</cell_line> ."}568{"id": "567", "text": "The cascade of events within the first few minutes of T cell stimulation has been well characterized .", "annotated_text": "The cascade of events within the first few minutes of <cell_type>T cell</cell_type> stimulation has been well characterized ."}569{"id": "568", "text": "Although many second messengers have been shown to be necessary and sufficient for T cell activation in a number of model systems , the rate-limiting step in peripheral T cells has not been demonstrated .", "annotated_text": "Although many second messengers have been shown to be necessary and sufficient for <cell_type>T cell</cell_type> activation in a number of model systems , the rate-limiting step in <cell_type>peripheral T cells</cell_type> has not been demonstrated ."}570{"id": "569", "text": "To model effective versus ineffective CD3 -mediated stimulation in peripheral T cells , we used two anti-CD3 mAbs that differ in their ability to stimulate purified T cells : OKT3 , which causes early second messenger generation but is unable to activate T cells without a second signal , and 64.1 , which stimulates T cell proliferation on its own .", "annotated_text": "To model effective versus ineffective <protein>CD3</protein> -mediated stimulation in <cell_type>peripheral T cells</cell_type> , we used two <protein>anti-CD3 mAbs</protein> that differ in their ability to stimulate <cell_type>purified T cells</cell_type> : <protein>OKT3</protein> , which causes early second messenger generation but is unable to activate <cell_type>T cells</cell_type> without a second signal , and <protein>64.1</protein> , which stimulates <cell_type>T cell</cell_type> proliferation on its own ."}571{"id": "570", "text": "We found that tyrosine kinase activity was similar for both mAbs over a period of hours .", "annotated_text": "We found that <protein>tyrosine kinase</protein> activity was similar for both <protein>mAbs</protein> over a period of hours ."}572{"id": "571", "text": "However , the inositol phosphate response was stronger for 64.1 than for OKT3 .", "annotated_text": "However , the inositol phosphate response was stronger for <protein>64.1</protein> than for <protein>OKT3</protein> ."}573{"id": "572", "text": "To tie these events to gene activation , we measured NF-kappa B and NF-AT activity in the nucleus after anti-CD3 stimulation .", "annotated_text": "To tie these events to gene activation , we measured <protein>NF-kappa B</protein> and <protein>NF-AT</protein> activity in the nucleus after <protein>anti-CD3</protein> stimulation ."}574{"id": "573", "text": "Both stimuli induced the appearance of the NF-kappa B components ( c-Rel , p65 ( RelA ) , and p50 ( NF-kappa B1 ) ) and NF-kappa B DNA binding activity in the nucleus .", "annotated_text": "Both stimuli induced the appearance of the <protein>NF-kappa B components</protein> ( <protein>c-Rel</protein> , <protein>p65</protein> ( <protein>RelA</protein> ) , and <protein>p50</protein> ( <protein>NF-kappa B1</protein> ) ) and <protein>NF-kappa B</protein> DNA binding activity in the nucleus ."}575{"id": "574", "text": "However , only 64.1 induced NF-AT in the nucleus , correlating with its ability to activate T cells .", "annotated_text": "However , only <protein>64.1</protein> induced <protein>NF-AT</protein> in the nucleus , correlating with its ability to activate <cell_type>T cells</cell_type> ."}576{"id": "575", "text": "Thus , NF-AT induction and IL-2 secretion were correlated with the levels of inositol phosphate release but not with gross levels of tyrosine kinase activity induced late following the response .", "annotated_text": "Thus , <protein>NF-AT</protein> induction and <protein>IL-2</protein> secretion were correlated with the levels of inositol phosphate release but not with gross levels of <protein>tyrosine kinase</protein> activity induced late following the response ."}577{"id": "576", "text": "On the other hand , NF-kappa B induction and IL-2 receptor expression occurred even with the smaller second messenger response generated by OKT3 .", "annotated_text": "On the other hand , <protein>NF-kappa B</protein> induction and <protein>IL-2</protein> receptor expression occurred even with the smaller second messenger response generated by <protein>OKT3</protein> ."}578{"id": "577", "text": "HLA-DR- , CD33+ , CD56+ , CD16- myeloid/natural killer cell acute leukemia : a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3 [ see comments ]", "annotated_text": "HLA-DR- , CD33+ , CD56+ , CD16- myeloid/natural killer cell acute leukemia : a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3 [ see comments ]"}579{"id": "578", "text": "We have identified and characterized a previously unrecognized form of acute leukemia that shares features of both myeloid and natural killer ( NK ) cells .", "annotated_text": "We have identified and characterized a previously unrecognized form of acute leukemia that shares features of both <cell_type>myeloid and natural killer ( NK ) cells</cell_type> ."}580{"id": "579", "text": "From a consecutive series of 350 cases of adult de novo acute myeloid leukemia ( AML ) , we identified 20 cases ( 6 % ) with a unique immunophenotype : CD33+ , CD56+ , CD11a+ , CD13lo , CD15lo , CD34+/- , HLA-DR - , CD16 - .", "annotated_text": "From a consecutive series of 350 cases of adult de novo acute myeloid leukemia ( AML ) , we identified 20 cases ( 6 % ) with a unique immunophenotype : CD33+ , CD56+ , CD11a+ , CD13lo , CD15lo , CD34+/- , <protein>HLA-DR</protein> - , <protein>CD16</protein> - ."}581{"id": "580", "text": "Multicolor flow cytometric assays confirmed the coexpression of myeloid ( CD33 , CD13 , CD15 ) and NK cell-associated ( CD56 ) antigens in each case , whereas reverse transcription polymerase chain reaction ( RT-PCR ) assays confirmed the identity of CD56 ( neural cell adhesion molecule ) in leukemic blasts .", "annotated_text": "Multicolor flow cytometric assays confirmed the coexpression of <protein>myeloid ( CD33 , CD13 , CD15 ) and NK cell-associated ( CD56 ) antigens</protein> in each case , whereas reverse transcription polymerase chain reaction ( RT-PCR ) assays confirmed the identity of <protein>CD56</protein> ( <protein>neural cell adhesion molecule</protein> ) in <cell_type>leukemic blasts</cell_type> ."}582{"id": "581", "text": "Although two cases expressed CD4 , no case expressed CD2 , CD3 , or CD8 and no case showed clonal rearrangement of genes encoding the T-cell receptor ( TCR beta , gamma , delta ) .", "annotated_text": "Although two cases expressed <protein>CD4</protein> , no case expressed <protein>CD2</protein> , <protein>CD3</protein> , or <protein>CD8</protein> and no case showed clonal rearrangement of genes encoding the <protein>T-cell receptor</protein> ( <protein>TCR beta , gamma , delta</protein> ) ."}583{"id": "582", "text": "Leukemic blasts in the majority of cases shared unique morphologic features ( deeply invaginated nuclear membranes , scant cytoplasm with fine azurophilic granularity , and finely granular Sudan black B and myeloperoxidase cytochemical reactivity ) that were remarkably similar to those of acute promyelocytic leukemia ( APL ) ; particularly the microgranular variant ( FAB AML-M3v ) .", "annotated_text": "Leukemic blasts in the majority of cases shared unique morphologic features ( deeply invaginated nuclear membranes , scant cytoplasm with fine azurophilic granularity , and finely granular Sudan black B and <protein>myeloperoxidase</protein> cytochemical reactivity ) that were remarkably similar to those of acute promyelocytic leukemia ( APL ) ; particularly the <protein>microgranular variant</protein> ( <protein>FAB AML-M3v</protein> ) ."}584{"id": "583", "text": "However , all 20 cases lacked the t ( 15 ; 17 ) and 17 cases tested lacked the promyelocytic/retinoic acid receptor alpha ( RAR alpha ) fusion transcript in RT-PCR assays ; 12 cases had 46 , XX or 46 , XY karyotypes , whereas 2 cases had abnormalities of chromosome 17q : 1 with del ( 17 ) ( q25 ) and the other with t ( 11 ; 17 ) ( q23 ; q21 ) and the promyelocytic leukemia zinc finger/RAR alpha fusion transcript .", "annotated_text": "However , all 20 cases lacked the t ( 15 ; 17 ) and 17 cases tested lacked the <rna>promyelocytic/retinoic acid receptor alpha ( RAR alpha ) fusion transcript</rna> in RT-PCR assays ; 12 cases had 46 , XX or 46 , XY karyotypes , whereas 2 cases had abnormalities of <dna>chromosome 17q</dna> : 1 with <dna>del ( 17 ) ( q25 )</dna> and the other with <dna>t ( 11 ; 17 ) ( q23 ; q21 )</dna> and the <rna>promyelocytic leukemia zinc finger/RAR alpha fusion transcript</rna> ."}585{"id": "584", "text": "All cases tested ( 6/20 ) , including the case with t ( 11 ; 17 ) , failed to differentiate in vitro in response to all-trans retinoic acid ( ATRA ) , suggesting that these cases may account for some APLs that have not shown a clinical response to ATRA .", "annotated_text": "All cases tested ( 6/20 ) , including the case with <dna>t ( 11 ; 17 )</dna> , failed to differentiate in vitro in response to all-trans retinoic acid ( ATRA ) , suggesting that these cases may account for some APLs that have not shown a clinical response to ATRA ."}586{"id": "585", "text": "Four of 6 cases tested showed functional NK cell-mediated cytotoxicity , suggesting a relationship between these unique CD33+ , CD56+ , CD16 -acute leukemias and normal CD56+ , CD16- NK precursor cells .", "annotated_text": "Four of 6 cases tested showed functional NK cell-mediated cytotoxicity , suggesting a relationship between these unique CD33+ , CD56+ , <protein>CD16</protein> -acute leukemias and <cell_type>normal CD56+ , CD16- NK precursor cells</cell_type> ."}587{"id": "586", "text": "Using a combination of panning and multiparameter flow cytometric sorting , we identified a normal CD56+ , CD33+ , CD16- counterpart cell at a frequency of 1 % to 2 % in the peripheral blood of healthy individuals .", "annotated_text": "Using a combination of panning and multiparameter flow cytometric sorting , we identified a <cell_type>normal CD56+ , CD33+ , CD16- counterpart cell</cell_type> at a frequency of 1 % to 2 % in the peripheral blood of healthy individuals ."}588{"id": "587", "text": "Our studies suggest that this form of acute leukemia may arise from transformation of a precursor cell common to both the myeloid and NK cell lineages ; thus we propose the designation myeloid/NK acute leukemia .", "annotated_text": "Our studies suggest that this form of acute leukemia may arise from transformation of a precursor cell common to both the <cell_type>myeloid and NK cell lineages</cell_type> ; thus we propose the designation myeloid/NK acute leukemia ."}589{"id": "588", "text": "Recognition of this new leukemic entity will be important in distinguishing these ATRA-nonresponsive cases from ATRA-responsive true APL .", "annotated_text": "Recognition of this new leukemic entity will be important in distinguishing these ATRA-nonresponsive cases from ATRA-responsive true APL ."}590{"id": "589", "text": "IL-4 down-regulates IL-2 - , IL-3 - , and GM-CSF -induced cytokine gene expression in peripheral blood monocytes .", "annotated_text": "<protein>IL-4</protein> down-regulates <protein>IL-2</protein> - , <protein>IL-3</protein> - , and <protein>GM-CSF</protein> -induced cytokine gene expression in peripheral blood monocytes ."}591{"id": "590", "text": "IL-4 , a product of the T-helper 0 ( Th0 ) and 2 ( Th2 ) subset , was originally described as a B-cell stimulatory factor and has subsequently been found to suppress IL-1 alpha , IL-1 beta , IL-6 , IL-8 , and TNF-alpha gene expression in monocytes stimulated with LPS , and to upregulate IL-1 receptor antagonist ( IL1-RA ) gene expression .", "annotated_text": "<protein>IL-4</protein> , a product of the <cell_type>T-helper 0 ( Th0 ) and 2 ( Th2 ) subset</cell_type> , was originally described as a <protein>B-cell stimulatory factor</protein> and has subsequently been found to suppress IL-1 alpha , IL-1 beta , IL-6 , IL-8 , and TNF-alpha gene expression in <cell_type>monocytes</cell_type> stimulated with LPS , and to upregulate <dna>IL-1 receptor antagonist ( IL1-RA ) gene</dna> expression ."}592{"id": "591", "text": "In this study we investigated the effect of IL-4 on the expression of cytokine genes in monocytes evoked by other T-helper cell cytokines : IL-2 , IL-3 , and GM-CSF .", "annotated_text": "In this study we investigated the effect of <protein>IL-4</protein> on the expression of <dna>cytokine genes</dna> in <cell_type>monocytes</cell_type> evoked by other <protein>T-helper cell cytokines</protein> : <protein>IL-2</protein> , <protein>IL-3</protein> , and <protein>GM-CSF</protein> ."}593{"id": "592", "text": "IL-4 down-regulated mRNA accumulation of the proinflammatory cytokines IL-1 beta , IL-8 , and TNF-alpha in monocytes stimulated with IL-2 , IL-3 , and GM-CSF .", "annotated_text": "<protein>IL-4</protein> down-regulated mRNA accumulation of the <protein>proinflammatory cytokines</protein> <protein>IL-1 beta</protein> , <protein>IL-8</protein> , and <protein>TNF-alpha</protein> in <cell_type>monocytes</cell_type> stimulated with <protein>IL-2</protein> , <protein>IL-3</protein> , and <protein>GM-CSF</protein> ."}594{"id": "593", "text": "IL-4 also suppressed the IL-2 -induced IL-6 mRNA expression .", "annotated_text": "<protein>IL-4</protein> also suppressed the <protein>IL-2</protein> -induced <protein>IL-6</protein> mRNA expression ."}595{"id": "594", "text": "Temporal analysis of the IL-4 down-regulatory effect on the IL-2- , IL-3- , or GM-CSF-induced proinflammatory cytokine gene expression in monocytes provided evidence that IL-4 acts predominantly on the post-transcriptional level .", "annotated_text": "Temporal analysis of the <protein>IL-4</protein> down-regulatory effect on the IL-2- , IL-3- , or GM-CSF-induced proinflammatory cytokine gene expression in <cell_type>monocytes</cell_type> provided evidence that <protein>IL-4</protein> acts predominantly on the post-transcriptional level ."}596{"id": "595", "text": "This was supported by the observation that the down-regulatory capacity of IL-4 appeared to be dependent on de novo protein synthesis .", "annotated_text": "This was supported by the observation that the down-regulatory capacity of <protein>IL-4</protein> appeared to be dependent on de novo protein synthesis ."}597{"id": "596", "text": "IL-4 did not exert significant influence on the induction of expression of IL-1-RA or various CSFs by IL-2 , IL-3 , and GM-CSF .", "annotated_text": "<protein>IL-4</protein> did not exert significant influence on the induction of expression of <protein>IL-1-RA</protein> or various <protein>CSFs</protein> by <protein>IL-2</protein> , <protein>IL-3</protein> , and <protein>GM-CSF</protein> ."}598{"id": "597", "text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"}599{"id": "598", "text": "Induction of proto-oncogene and cytokine expression in human peripheral blood monocytes and the monocytic cell line THP-1 after stimulation with mycoplasma-derived material MDHM .", "annotated_text": "Induction of <dna>proto-oncogene</dna> and <protein>cytokine</protein> expression in human peripheral blood <cell_type>monocytes</cell_type> and the <cell_line>monocytic cell line</cell_line> <cell_line>THP-1</cell_line> after stimulation with mycoplasma-derived material MDHM ."}600{"id": "599", "text": "Mycoplasma fermentans-derived high-molecular-weight material ( MDHM ) was originally described to induce differentiation of murine thymocytes to cytolytic effector T-cells by stimulating IL-6 release from adherent cells .", "annotated_text": "Mycoplasma fermentans-derived high-molecular-weight material ( MDHM ) was originally described to induce differentiation of <cell_type>murine thymocytes</cell_type> to <cell_type>cytolytic effector T-cells</cell_type> by stimulating <protein>IL-6</protein> release from <cell_type>adherent cells</cell_type> ."}601{"id": "600", "text": "This study shows that human peripheral blood monocytes ( PBMo ) also respond to MDHM with increases in IL-1 beta , IL-6 and TNF alpha expression , both at the mRNA and protein level .", "annotated_text": "This study shows that human peripheral blood <cell_type>monocytes</cell_type> ( <cell_type>PBMo</cell_type> ) also respond to MDHM with increases in <protein>IL-1 beta</protein> , <protein>IL-6</protein> and <protein>TNF alpha</protein> expression , both at the mRNA and protein level ."}602{"id": "601", "text": "The induced expression of IL-1 beta and TNF alpha mRNA in the monocytic THP-1 cell line increased as quickly as in primary cells .", "annotated_text": "The induced expression of <rna>IL-1 beta and TNF alpha mRNA</rna> in the monocytic <cell_line>THP-1 cell line</cell_line> increased as quickly as in <cell_type>primary cells</cell_type> ."}603{"id": "602", "text": "In contrast to PBMo , THP-1 and 14 other monocytic/myeloid leukemia-derived cell lines did not secrete measurable amounts of the cytokines upon treatment with MDHM .", "annotated_text": "In contrast to <cell_type>PBMo</cell_type> , <cell_line>THP-1</cell_line> and 14 other <cell_line>monocytic/myeloid leukemia-derived cell lines</cell_line> did not secrete measurable amounts of the <protein>cytokines</protein> upon treatment with MDHM ."}604{"id": "603", "text": "IL-1 beta and IL-6 genes contain AP-1 binding sites as regulatory elements , the AP-1 protein being composed of c-jun and c-fos gene products .", "annotated_text": "<dna>IL-1 beta and IL-6 genes</dna> contain <dna>AP-1 binding sites</dna> as <dna>regulatory elements</dna> , the <protein>AP-1</protein> protein being composed of <protein>c-jun and c-fos gene products</protein> ."}605{"id": "604", "text": "In THP-1 cells c-jun mRNA expression increased after incubation with MDHM while positive c-fos expression remained unaffected .", "annotated_text": "In <cell_line>THP-1 cells</cell_line> <rna>c-jun mRNA</rna> expression increased after incubation with MDHM while positive <dna>c-fos</dna> expression remained unaffected ."}606{"id": "605", "text": "Although these data suggest AP-1 regulated cytokine mRNA expression , results from PBMo are not in accordance with this notion .", "annotated_text": "Although these data suggest <protein>AP-1</protein> regulated <protein>cytokine</protein> mRNA expression , results from <cell_type>PBMo</cell_type> are not in accordance with this notion ."}607{"id": "606", "text": "In the primary cells MDHM-induced elevation of cytokine mRNA levels was preceded by a downregulation of c-fos expression while positive c-jun expression was not modulated .", "annotated_text": "In the <cell_type>primary cells</cell_type> MDHM-induced elevation of <rna>cytokine mRNA</rna> levels was preceded by a downregulation of <dna>c-fos</dna> expression while positive <dna>c-jun</dna> expression was not modulated ."}608{"id": "607", "text": "c-myc mRNA expression , constitutively high in THP-1 cells , was induced in MDHM-stimulated PBMo .", "annotated_text": "<rna>c-myc mRNA</rna> expression , constitutively high in <cell_line>THP-1 cells</cell_line> , was induced in MDHM-stimulated <cell_type>PBMo</cell_type> ."}609{"id": "608", "text": "In conclusion , MDHM-stimulated induction of cytokine mRNA expression was accompanied by different proto-oncogene responses in PBMo and THP-1 cells .", "annotated_text": "In conclusion , MDHM-stimulated induction of <rna>cytokine mRNA</rna> expression was accompanied by different <dna>proto-oncogene</dna> responses in <cell_type>PBMo</cell_type> and <cell_line>THP-1 cells</cell_line> ."}610{"id": "609", "text": "These differences may represent different regulatory pathways of the two cell systems .", "annotated_text": "These differences may represent different regulatory pathways of the two cell systems ."}611{"id": "610", "text": "Alternatively , these data support the notion that neither AP-1 nor the c-myc protein are involved in the MDHM-induced increase in IL-1 beta , IL-6 or TNF alpha mRNA levels .", "annotated_text": "Alternatively , these data support the notion that neither <protein>AP-1</protein> nor the <protein>c-myc protein</protein> are involved in the MDHM-induced increase in IL-1 beta , IL-6 or TNF alpha mRNA levels ."}612{"id": "611", "text": "Furthermore , the present results demonstrate clearly that mycoplasma products can have a profound impact on the activation status of eukaryotic cells .", "annotated_text": "Furthermore , the present results demonstrate clearly that <protein>mycoplasma products</protein> can have a profound impact on the activation status of <cell_type>eukaryotic cells</cell_type> ."}613{"id": "612", "text": "Novel membrane receptors for aldosterone in human lymphocytes : a 50 kDa protein on SDS-PAGE .", "annotated_text": "<protein>Novel membrane receptors</protein> for aldosterone in <cell_type>human lymphocytes</cell_type> : a <protein>50 kDa protein</protein> on SDS-PAGE ."}614{"id": "613", "text": "Fast in vitro effects of aldosterone on the Na+/H ( + ) -exchanger , inositoltrisphosphate generation and corresponding specific binding to plasma membranes at Kd-values of approximately 0.1 nM have been found in human mononuclear leukocytes and vascular smooth muscle cells .", "annotated_text": "Fast in vitro effects of aldosterone on the <protein>Na+/H ( + ) -exchanger</protein> , inositoltrisphosphate generation and corresponding specific binding to plasma membranes at Kd-values of approximately 0.1 nM have been found in <cell_type>human mononuclear leukocytes</cell_type> and <cell_type>vascular smooth muscle cells</cell_type> ."}615{"id": "614", "text": "The novel aldosterone membrane receptor was analyzed on SDS-PAGE after labeling of microsomal membranes from human mononuclear leukocytes with a [ 125I ] -aldosterone-derivative by use of BASED as a photoactivatable crosslinker .", "annotated_text": "The novel aldosterone membrane receptor was analyzed on SDS-PAGE after labeling of microsomal membranes from <cell_type>human mononuclear leukocytes</cell_type> with a [ 125I ] -aldosterone-derivative by use of BASED as a photoactivatable crosslinker ."}616{"id": "615", "text": "Binding of 1 nM [ 125I ] -aldosterone was found at a molecular weight of approximately 50 kDa which was absent with 1 microM cold aldosterone , but not cortisol in the binding media .", "annotated_text": "Binding of 1 nM [ 125I ] -aldosterone was found at a molecular weight of approximately 50 kDa which was absent with 1 microM cold aldosterone , but not cortisol in the binding media ."}617{"id": "616", "text": "This aldosterone-selectivity is typical and discriminatory for the new aldosterone membrane receptor .", "annotated_text": "This aldosterone-selectivity is typical and discriminatory for the new <protein>aldosterone membrane receptor</protein> ."}618{"id": "617", "text": "Solubilization of the receptor protein from membranes by high salt concentrations ( 1 M NaCl , 1 mM EDTA ) was not achieved .", "annotated_text": "Solubilization of the <protein>receptor protein</protein> from membranes by high salt concentrations ( 1 M NaCl , 1 mM EDTA ) was not achieved ."}619{"id": "618", "text": "It , thus , appears as an integral membrane protein .", "annotated_text": "It , thus , appears as an <protein>integral membrane protein</protein> ."}620{"id": "619", "text": "Dithiothreitol , a sulfhydryl agent , does not reduce specific aldosterone binding indicating the absence of SH-groups in the binding domain or sensitive structures of the receptors .", "annotated_text": "Dithiothreitol , a sulfhydryl agent , does not reduce specific aldosterone binding indicating the absence of <protein>SH-groups</protein> in the <protein>binding domain</protein> or sensitive structures of the receptors ."}621{"id": "620", "text": "The results are the first to characterize the novel membrane receptor for aldosterone with regard to molecular weight and basic properties .", "annotated_text": "The results are the first to characterize the <protein>novel membrane receptor</protein> for aldosterone with regard to molecular weight and basic properties ."}622{"id": "621", "text": "These findings and other related results are reviewed here .", "annotated_text": "These findings and other related results are reviewed here ."}623{"id": "622", "text": "A transcriptional regulatory element is associated with a nuclease-hypersensitive site in the pol gene of human immunodeficiency virus type 1 .", "annotated_text": "A <dna>transcriptional regulatory element</dna> is associated with a <dna>nuclease-hypersensitive site</dna> in the <dna>pol gene</dna> of human immunodeficiency virus type 1 ."}624{"id": "623", "text": "Analysis of the chromatin organization of the integrated human immunodeficiency virus type 1 ( HIV-1 ) genome has previously revealed a major constitutive DNase I-hypersensitive site associated with the pol gene ( E. Verdin , J. Virol. 65 : 6790-6799 , 1991 ) .", "annotated_text": "Analysis of the chromatin organization of the integrated <dna>human immunodeficiency virus type 1 ( HIV-1 ) genome</dna> has previously revealed a <dna>major constitutive DNase I-hypersensitive site</dna> associated with the <dna>pol gene</dna> ( E. Verdin , J. Virol. 65 : 6790-6799 , 1991 ) ."}625{"id": "624", "text": "In the present report , high-resolution mapping of this site with DNase I and micrococcal nuclease identified a nucleosome-free region centered around nucleotides ( nt ) 4490 to 4766 .", "annotated_text": "In the present report , high-resolution mapping of this site with <protein>DNase I</protein> and <protein>micrococcal nuclease</protein> identified a <dna>nucleosome-free region</dna> centered around <dna>nucleotides ( nt ) 4490 to 4766</dna> ."}626{"id": "625", "text": "A 500-bp fragment encompassing this hypersensitive site ( nt 4481 to 4982 ) exhibited transcription-enhancing activity ( two- to threefold ) when it was cloned in its natural position with respect to the HIV-1 promoter after transient transfection in U937 and CEM cells .", "annotated_text": "A <dna>500-bp fragment</dna> encompassing this <dna>hypersensitive site</dna> ( <dna>nt 4481 to 4982</dna> ) exhibited transcription-enhancing activity ( two- to threefold ) when it was cloned in its natural position with respect to the <dna>HIV-1 promoter</dna> after transient transfection in <cell_line>U937</cell_line> and <cell_line>CEM cells</cell_line> ."}627{"id": "626", "text": "Using in vitro footprinting and gel shift assays , we have identified four distinct binding sites for nuclear proteins within this positive regulatory element .", "annotated_text": "Using in vitro footprinting and gel shift assays , we have identified four distinct <dna>binding sites</dna> for <protein>nuclear proteins</protein> within this <dna>positive regulatory element</dna> ."}628{"id": "627", "text": "Site B ( nt 4519 to 4545 ) specifically bound four distinct nuclear protein complexes : a ubiquitous factor , a T-cell-specific factor , a B-cell-specific factor , and the monocyte/macrophage- and B-cell-specific transcription factor PU.1/Spi-1 .", "annotated_text": "<dna>Site B</dna> ( <dna>nt 4519 to 4545</dna> ) specifically bound four distinct <protein>nuclear protein complexes</protein> : a <protein>ubiquitous factor</protein> , a <protein>T-cell-specific factor</protein> , a <protein>B-cell-specific factor</protein> , and the <protein>monocyte/macrophage- and B-cell-specific transcription factor</protein> <protein>PU.1/Spi-1</protein> ."}629{"id": "628", "text": "In most HIV-1 isolates in which this PU box was not conserved , it was replaced by a binding site for the related factor Ets1 .", "annotated_text": "In most HIV-1 isolates in which this <dna>PU box</dna> was not conserved , it was replaced by a <dna>binding site</dna> for the related factor <protein>Ets1</protein> ."}630{"id": "629", "text": "Factors binding to site C ( nt 4681 to 4701 ) had a DNA-binding specificity similar to that of factors binding to site B , except for PU.1/Spi-1 .", "annotated_text": "Factors binding to <dna>site C</dna> ( <dna>nt 4681 to 4701</dna> ) had a DNA-binding specificity similar to that of factors binding to <dna>site B</dna> , except for <protein>PU.1/Spi-1</protein> ."}631{"id": "630", "text": "A GC box containing a binding site for Sp1 was identified ( nt 4623 to 4631 ) .", "annotated_text": "A <dna>GC box</dna> containing a <dna>binding site</dna> for <protein>Sp1</protein> was identified ( <dna>nt 4623 to 4631</dna> ) ."}632{"id": "631", "text": "Site D ( nt 4816 to 4851 ) specifically bound a ubiquitously expressed factor .", "annotated_text": "<dna>Site D</dna> ( <dna>nt 4816 to 4851</dna> ) specifically bound a <protein>ubiquitously expressed factor</protein> ."}633{"id": "632", "text": "These results identify a transcriptional regulatory element associated with a nuclease-hypersensitive site in the pol gene of HIV-1 and suggest that its activity may be controlled by a complex interplay of cis- regulatory elements .", "annotated_text": "These results identify a <dna>transcriptional regulatory element</dna> associated with a <dna>nuclease-hypersensitive site</dna> in the <dna>pol gene</dna> of HIV-1 and suggest that its activity may be controlled by a complex interplay of cis- <dna>regulatory elements</dna> ."}634{"id": "633", "text": "Expression of v-src in T cells correlates with nuclear expression of NF-kappa B .", "annotated_text": "Expression of <dna>v-src</dna> in <cell_type>T cells</cell_type> correlates with nuclear expression of <protein>NF-kappa B</protein> ."}635{"id": "634", "text": "NF-kappa B is a rapidly inducible transcriptional activator that responds to a variety of signals and influences the expression of many genes involved in the immune response .", "annotated_text": "<protein>NF-kappa B</protein> is a rapidly inducible <dna>transcriptional activator</dna> that responds to a variety of signals and influences the expression of many genes involved in the immune response ."}636{"id": "635", "text": "Protein tyrosine kinases transmit signals from cytokine and immune receptors .", "annotated_text": "Protein <protein>tyrosine kinases</protein> transmit signals from <protein>cytokine and immune receptors</protein> ."}637{"id": "636", "text": "Very little information exists linking these two important classes of signaling molecules .", "annotated_text": "Very little information exists linking these two important classes of <protein>signaling molecules</protein> ."}638{"id": "637", "text": "We now demonstrate that v-src expression correlates with nuclear expression of a kappa B binding complex similar to that induced by phorbol ester and ionomycin , as detected by electrophoretic mobility shift assay using a variety of kappa B sites .", "annotated_text": "We now demonstrate that <dna>v-src</dna> expression correlates with nuclear expression of a <protein>kappa B binding complex</protein> similar to that induced by phorbol ester and ionomycin , as detected by electrophoretic mobility shift assay using a variety of <dna>kappa B sites</dna> ."}639{"id": "638", "text": "This complex was blocked by the tyrosine kinase inhibitor , herbimycin A .", "annotated_text": "This complex was blocked by the <protein>tyrosine kinase</protein> inhibitor , herbimycin A ."}640{"id": "639", "text": "The v-src-induced complex comprised the p50 and p65 components of NF-kappa B , as determined by supershift and immunoblot analysis .", "annotated_text": "The <protein>v-src-induced complex</protein> comprised the <protein>p50</protein> and <protein>p65</protein> components of <protein>NF-kappa B</protein> , as determined by supershift and immunoblot analysis ."}641{"id": "640", "text": "As a functional correlate of this finding , transient co-transfection of HIV-1 LTR reporter constructs in a different T cell line demonstrated that v-src activated this promoter in a kappa B-dependent manner .", "annotated_text": "As a functional correlate of this finding , transient co-transfection of <dna>HIV-1 LTR reporter constructs</dna> in a different <cell_line>T cell line</cell_line> demonstrated that <dna>v-src</dna> activated this <protein>promoter</protein> in a kappa B-dependent manner ."}642{"id": "641", "text": "We found that transactivation of the HIV-1 LTR by v-src was more sensitive to mutations of the proximal , rather than the distal , kappa B element .", "annotated_text": "We found that transactivation of the <dna>HIV-1 LTR</dna> by <dna>v-src</dna> was more sensitive to mutations of the proximal , rather than the distal , <dna>kappa B element</dna> ."}643{"id": "642", "text": "The implications for T cell receptor signaling and HIV-1 gene expression are considered .", "annotated_text": "The implications for <protein>T cell receptor</protein> signaling and <dna>HIV-1 gene</dna> expression are considered ."}644{"id": "643", "text": "trans-activation of the HIV promoter by a cDNA and its genomic clones of human herpesvirus-6 .", "annotated_text": "trans-activation of the <dna>HIV promoter</dna> by a cDNA and its genomic clones of human herpesvirus-6 ."}645{"id": "644", "text": "Human herpesvirus 6 ( HHV-6 ) is a lymphotropic herpesvirus , and in vitro , it can productively infect human CD4+ T cells as HIV-1 .", "annotated_text": "Human herpesvirus 6 ( HHV-6 ) is a lymphotropic herpesvirus , and in vitro , it can productively infect human <cell_line>CD4+ T cells</cell_line> as HIV-1 ."}646{"id": "645", "text": "Co-infection of T cells by HIV-1 and HHV-6 can lead to both activation of the HIV-1 promoter and acceleration of the cytopathic effects .", "annotated_text": "Co-infection of <cell_type>T cells</cell_type> by HIV-1 and HHV-6 can lead to both activation of the <dna>HIV-1 promoter</dna> and acceleration of the cytopathic effects ."}647{"id": "646", "text": "An HHV-6 ( GS ) cDNA clone , pCD41 , encoding for a 41-kDa nuclear protein was identified and characterized previously ( Chang and Balachandran , J. Virol. 65 , 2884-2894 and 7085 , 1991 ) .", "annotated_text": "An <dna>HHV-6 ( GS ) cDNA clone</dna> , <dna>pCD41</dna> , encoding for a <protein>41-kDa nuclear protein</protein> was identified and characterized previously ( Chang and Balachandran , J. Virol. 65 , 2884-2894 and 7085 , 1991 ) ."}648{"id": "647", "text": "Sequence analyses show that this protein has significant homology with the human cytomegalovirus UL44 gene coding for the ICP36 family of early-late-class phosphoprotein .", "annotated_text": "Sequence analyses show that this protein has significant homology with the <dna>human cytomegalovirus UL44 gene</dna> coding for the <protein>ICP36 family</protein> of <protein>early-late-class phosphoprotein</protein> ."}649{"id": "648", "text": "Using this cDNA as the probe , a 3.8-kb EcoRI genomic fragment encoding the HHV-6 ( GS ) P41 was cloned and designated as pGD41 .", "annotated_text": "Using this <dna>cDNA</dna> as the probe , a <dna>3.8-kb EcoRI genomic fragment</dna> encoding the <protein>HHV-6 ( GS ) P41</protein> was cloned and designated as <dna>pGD41</dna> ."}650{"id": "649", "text": "When cotransfected with the HIV LTR CAT into CV-1 cells , both the pCD41 and pGD41 clones trans-activated the HIV LTR .", "annotated_text": "When cotransfected with the <dna>HIV LTR CAT</dna> into <cell_line>CV-1 cells</cell_line> , both the <dna>pCD41</dna> and <dna>pGD41</dna> clones trans-activated the <dna>HIV LTR</dna> ."}651{"id": "650", "text": "Sequence analyses of pCD41 indicate that there are two potential open reading frames ( ORFs ) , A and B , which are homologous to the ORFs found in the genomic clone pGD41 .", "annotated_text": "Sequence analyses of <dna>pCD41</dna> indicate that there are two potential <dna>open reading frames</dna> ( <dna>ORFs</dna> ) , <dna>A</dna> and <dna>B</dna> , which are homologous to the <dna>ORFs</dna> found in the genomic clone <dna>pGD41</dna> ."}652{"id": "651", "text": "Deletion constructs of the pCD41 clone demonstrated that ORF-A was critical for the HIV LTR activation .", "annotated_text": "Deletion constructs of the <dna>pCD41 clone</dna> demonstrated that <protein>ORF-A</protein> was critical for the <dna>HIV LTR</dna> activation ."}653{"id": "652", "text": "Deletion analyses of the pCD41 ORF-A and the use of promoter constructs further mapped an internal functional promoter within the pCD41 sequence that can direct the synthesis of the trans-activating protein .", "annotated_text": "Deletion analyses of the <dna>pCD41</dna> <protein>ORF-A</protein> and the use of <dna>promoter constructs</dna> further mapped an internal functional promoter within the <dna>pCD41</dna> sequence that can direct the synthesis of the <protein>trans-activating protein</protein> ."}654{"id": "653", "text": "By using HIV LTR deletion mutants , the NF-kappa B binding sites were found to be critical for response to the pCD41 trans-activation .", "annotated_text": "By using <dna>HIV LTR deletion mutants</dna> , the <protein>NF-kappa B</protein> <dna>binding sites</dna> were found to be critical for response to the <dna>pCD41</dna> trans-activation ."}655{"id": "654", "text": "CD14 -mediated translocation of nuclear factor-kappa B induced by lipopolysaccharide does not require tyrosine kinase activity .", "annotated_text": "<protein>CD14</protein> -mediated translocation of <protein>nuclear factor-kappa B</protein> induced by lipopolysaccharide does not require <protein>tyrosine kinase</protein> activity ."}656{"id": "655", "text": "During the course of serious bacterial infections , lipopolysaccharide ( LPS ) is believed to interact with macrophage receptors , resulting in the generation of inflammatory mediators and systemic symptoms including hemodynamic instability and shock .", "annotated_text": "During the course of serious bacterial infections , lipopolysaccharide ( LPS ) is believed to interact with <protein>macrophage receptors</protein> , resulting in the generation of inflammatory mediators and systemic symptoms including hemodynamic instability and shock ."}657{"id": "656", "text": "CD14 , a glycosylphosphatidylinositol-linked antigen , functions as an LPS signaling receptor .", "annotated_text": "<protein>CD14</protein> , a <protein>glycosylphosphatidylinositol-linked antigen</protein> , functions as an <protein>LPS signaling receptor</protein> ."}658{"id": "657", "text": "A critical issue concerns the mechanism by which CD14 , which has no transmembrane domain , transduces its signal following LPS binding .", "annotated_text": "A critical issue concerns the mechanism by which <protein>CD14</protein> , which has no <protein>transmembrane domain</protein> , transduces its signal following LPS binding ."}659{"id": "658", "text": "Recently , investigators have hypothesized that CD14 -mediated signaling is effected through a receptor-associated tyrosine kinase ( TK ) , suggesting a multicomponent receptor model of LPS signaling .", "annotated_text": "Recently , investigators have hypothesized that <protein>CD14</protein> -mediated signaling is effected through a receptor-associated <protein>tyrosine kinase</protein> ( TK ) , suggesting a multicomponent receptor model of LPS signaling ."}660{"id": "659", "text": "Wild-type Chinese hamster ovary ( CHO ) -K1 cells can be activated by endotoxin to release arachidonate following transfection with human CD14 ( CHO/CD14 ) .", "annotated_text": "Wild-type <cell_line>Chinese hamster ovary ( CHO ) -K1 cells</cell_line> can be activated by endotoxin to release arachidonate following transfection with human <protein>CD14</protein> ( <protein>CHO/CD14</protein> ) ."}661{"id": "660", "text": "Nuclear translocation of cytosolic NF-kappa B is correlated with a number of LPS-inducible responses .", "annotated_text": "Nuclear translocation of cytosolic NF-kappa B is correlated with a number of LPS-inducible responses ."}662{"id": "661", "text": "We sought to determine if this pathway were present in CHO/CD14 cells and to elucidate the relationship of NF-kappa B activation to the CD14 receptor system .", "annotated_text": "We sought to determine if this pathway were present in <cell_line>CHO/CD14 cells</cell_line> and to elucidate the relationship of <protein>NF-kappa B</protein> activation to the <protein>CD14</protein> receptor system ."}663{"id": "662", "text": "LPS-stimulated translocation of NF-kappa B in CHO/CD14 cells resembled the same response in the murine macrophage-like cell line RAW 264.7 .", "annotated_text": "LPS-stimulated translocation of <protein>NF-kappa B</protein> in <cell_line>CHO/CD14 cells</cell_line> resembled the same response in the <cell_line>murine macrophage-like cell line</cell_line> <cell_line>RAW 264.7</cell_line> ."}664{"id": "663", "text": "Protein synthesis inhibitors and corticosteroids , which suppress arachidonate release and the synthesis of proinflammatory cytokines , had no effect on translocation of NF-kappa B in CHO/ CD14 or RAW 264.7 cells , demonstrating that NF-kappa B translocation is an early event .", "annotated_text": "Protein synthesis inhibitors and corticosteroids , which suppress arachidonate release and the synthesis of <protein>proinflammatory cytokines</protein> , had no effect on translocation of <protein>NF-kappa B</protein> in CHO/ <protein>CD14</protein> or <cell_line>RAW 264.7 cells</cell_line> , demonstrating that <protein>NF-kappa B</protein> translocation is an early event ."}665{"id": "664", "text": "Although TK activity was consistently observed by immunoblotting extracts from activated RAW 264.7 cells , LPS-induced phosphotyrosine residues were not observed from similarly treated CHO/CD14 cells .", "annotated_text": "Although TK activity was consistently observed by immunoblotting extracts from activated <cell_line>RAW 264.7 cells</cell_line> , LPS-induced phosphotyrosine residues were not observed from similarly treated <cell_line>CHO/CD14 cells</cell_line> ."}666{"id": "665", "text": "Furthermore , the TK inhibitors herbimycin A and genistein failed to inhibit translocation of NF-kappa B in CHO/CD14 or RAW 264.7 cells , although both of these agents inhibited LPS-induced TK activity in RAW 264.7 cells .", "annotated_text": "Furthermore , the TK inhibitors herbimycin A and genistein failed to inhibit translocation of <protein>NF-kappa B</protein> in <cell_line>CHO/CD14</cell_line> or <cell_line>RAW 264.7 cells</cell_line> , although both of these agents inhibited LPS-induced TK activity in <cell_line>RAW 264.7 cells</cell_line> ."}667{"id": "666", "text": "These results imply that TK activity is not obligatory for CD14 -mediated signal transduction to occur in response to LPS .", "annotated_text": "These results imply that TK activity is not obligatory for <protein>CD14</protein> -mediated signal transduction to occur in response to LPS ."}668{"id": "667", "text": "Signals transduced through the CD4 molecule on T lymphocytes activate NF-kappa B .", "annotated_text": "Signals transduced through the <protein>CD4 molecule</protein> on <cell_type>T lymphocytes</cell_type> activate <protein>NF-kappa B</protein> ."}669{"id": "668", "text": "We have demonstrated that native envelope glycoproteins of HIV-1 , gp160 can induce activation of the transcription factor , NF-kappa B .", "annotated_text": "We have demonstrated that <protein>native envelope glycoproteins</protein> of HIV-1 , gp160 can induce activation of the <protein>transcription factor</protein> , <protein>NF-kappa B</protein> ."}670{"id": "669", "text": "The stimulatory effects of gp160 are mediated through the CD4 molecule , since pretreatment with soluble CD4 abrogates its activity .", "annotated_text": "The stimulatory effects of gp160 are mediated through the <protein>CD4 molecule</protein> , since pretreatment with soluble <protein>CD4</protein> abrogates its activity ."}671{"id": "670", "text": "The gp160-induced NF-kappa B complex consists of p65 , p50 and c-rel proteins .", "annotated_text": "The <protein>gp160-induced NF-kappa B complex</protein> consists of <protein>p65</protein> , <protein>p50</protein> and <protein>c-rel proteins</protein> ."}672{"id": "671", "text": "The stimulatory effect of gp160 on NF-kappa B activation is protein synthesis independent , is dependent upon protein tyrosine phosphorylation , and abrogated by inhibitors of protein kinase C .", "annotated_text": "The stimulatory effect of gp160 on <protein>NF-kappa B</protein> activation is protein synthesis independent , is dependent upon protein tyrosine phosphorylation , and abrogated by inhibitors of <protein>protein kinase C</protein> ."}673{"id": "672", "text": "The gp160-mediated activation of NF-kappa B in CD4 positive T cells may be involved in biological effects , e.g. , enhanced HIV replication , hypergammaglobulinemia , increased cytokine secretion , hypercellularity in bone marrow and apoptosis .", "annotated_text": "The gp160-mediated activation of <protein>NF-kappa B</protein> in <cell_type>CD4 positive T cells</cell_type> may be involved in biological effects , e.g. , enhanced HIV replication , hypergammaglobulinemia , increased <protein>cytokine</protein> secretion , hypercellularity in bone marrow and apoptosis ."}674{"id": "673", "text": "No evidence for the expression of the progesterone receptor on peripheral blood lymphocytes during pregnancy [ see comments ]", "annotated_text": "No evidence for the expression of the <protein>progesterone receptor</protein> on <cell_type>peripheral blood lymphocytes</cell_type> during pregnancy [ see comments ]"}675{"id": "674", "text": "The expression of the progesterone receptor in human peripheral blood lymphocytes was analysed , using an enzyme linked immunosorbent assay ( Abbott PgR-EIA monoclonal ) , in order to evaluate its prognostic character in the context of spontaneous abortion .", "annotated_text": "The expression of the <protein>progesterone receptor</protein> in <cell_type>human peripheral blood lymphocytes</cell_type> was analysed , using an enzyme linked immunosorbent assay ( Abbott PgR-EIA monoclonal ) , in order to evaluate its prognostic character in the context of spontaneous abortion ."}676{"id": "675", "text": "Cytosols were prepared from lymphocytes of 24 healthy pregnant women ( 11 first , 10 second and three third trimester ) , seven healthy non-pregnant women , nine women with recurrent spontaneous abortion , and six healthy men .", "annotated_text": "Cytosols were prepared from lymphocytes of 24 healthy pregnant women ( 11 first , 10 second and three third trimester ) , seven healthy non-pregnant women , nine women with recurrent spontaneous abortion , and six healthy men ."}677{"id": "676", "text": "In addition , a human breast carcinoma cell line ( ZR-75-1 ) , which expresses the progesterone receptor , was analysed throughout .", "annotated_text": "In addition , a <cell_line>human breast carcinoma cell line</cell_line> ( <cell_line>ZR-75-1</cell_line> ) , which expresses the <protein>progesterone receptor</protein> , was analysed throughout ."}678{"id": "677", "text": "The ZR-75-1 cell line showed an expression of 642 fmol/mg whereas lymphocytes of pregnant women showed an expression < or = 4 fmol/mg .", "annotated_text": "The <cell_line>ZR-75-1 cell line</cell_line> showed an expression of 642 fmol/mg whereas lymphocytes of pregnant women showed an expression < or = 4 fmol/mg ."}679{"id": "678", "text": "Lymphocytes of non-pregnant women , women with threatened pre-term delivery , and men showed equivalent levels : 3 +/- 1 , 3 +/- 2 and 5 +/- 4 fmol/mg respectively .", "annotated_text": "<cell_type>Lymphocytes</cell_type> of non-pregnant women , women with threatened pre-term delivery , and men showed equivalent levels : 3 +/- 1 , 3 +/- 2 and 5 +/- 4 fmol/mg respectively ."}680{"id": "679", "text": "These results show that there is no evidence of specific expression of the progesterone receptor in pregnancy and exclude any prognostic character in spontaneous abortion .", "annotated_text": "These results show that there is no evidence of specific expression of the <protein>progesterone receptor</protein> in pregnancy and exclude any prognostic character in spontaneous abortion ."}681{"id": "680", "text": "A role for the progesterone receptor in the mechanism of the known effect of progesterone on peripheral blood lymphocytes is also excluded .", "annotated_text": "A role for the <protein>progesterone receptor</protein> in the mechanism of the known effect of progesterone on <cell_type>peripheral blood lymphocytes</cell_type> is also excluded ."}682{"id": "681", "text": "Tolerance to lipopolysaccharide involves mobilization of nuclear factor kappa B with predominance of p50 homodimers .", "annotated_text": "Tolerance to lipopolysaccharide involves mobilization of <protein>nuclear factor kappa B</protein> with predominance of <protein>p50</protein> homodimers ."}683{"id": "682", "text": "Stimulation of the human monocytic cell line Mono Mac 6 with lipopolysaccharide ( LPS ) leads to rapid and transient expression of cytokines like tumor necrosis factor ( TNF ) .", "annotated_text": "Stimulation of the <cell_line>human monocytic cell line</cell_line> <cell_line>Mono Mac 6</cell_line> with lipopolysaccharide ( LPS ) leads to rapid and transient expression of <protein>cytokines</protein> like <protein>tumor necrosis factor</protein> ( <protein>TNF</protein> ) ."}684{"id": "683", "text": "When such cells are precultured for 2 days with a low dose of LPS ( 20 ng/ml ) followed by stimulation with a high dose of LPS ( 1 microgram/ml ) , expression of the TNF gene is minimal , i.e. the cells are tolerant .", "annotated_text": "When such cells are precultured for 2 days with a low dose of LPS ( 20 ng/ml ) followed by stimulation with a high dose of LPS ( 1 microgram/ml ) , expression of the <dna>TNF gene</dna> is minimal , i.e. the cells are tolerant ."}685{"id": "684", "text": "In nuclear run-on analysis , such tolerant cells show only a low degree of transcription , indicating that tolerance operates at or upstream of the transcription level .", "annotated_text": "In nuclear run-on analysis , such <cell_type>tolerant cells</cell_type> show only a low degree of transcription , indicating that tolerance operates at or upstream of the transcription level ."}686{"id": "685", "text": "The CD14 LPS receptor is , however , up-regulated ( not down-regulated ) in tolerant cells , and LPS can , in fact , still lead to activation of tolerant cells as evidenced by mobilization of the transcription factor nuclear factor kappa B ( NF-kappa B ) .", "annotated_text": "The <protein>CD14</protein> LPS receptor is , however , up-regulated ( not down-regulated ) in <cell_line>tolerant cells</cell_line> , and LPS can , in fact , still lead to activation of <cell_line>tolerant cells</cell_line> as evidenced by mobilization of the <protein>transcription factor</protein> <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) ."}687{"id": "686", "text": "Resolution of the NF-kappa B complex in gel shift analysis shows that the binding protein , mobilized in naive Mono Mac 6 cells , consists mainly of p50-p65 heterodimers , while in tolerant cells , the p50 homodimer is predominant .", "annotated_text": "Resolution of the <protein>NF-kappa B complex</protein> in gel shift analysis shows that the <protein>binding protein</protein> , mobilized in <cell_line>naive Mono Mac 6 cells</cell_line> , consists mainly of <protein>p50-p65 heterodimers</protein> , while in <cell_line>tolerant cells</cell_line> , the <protein>p50 homodimer</protein> is predominant ."}688{"id": "687", "text": "This increase in p50 homodimers coincides with an increase in p105 mRNA , suggestive of a transcriptional up-regulation of p50 .", "annotated_text": "This increase in <protein>p50 homodimers</protein> coincides with an increase in <rna>p105 mRNA</rna> , suggestive of a transcriptional up-regulation of <protein>p50</protein> ."}689{"id": "688", "text": "Reporter gene analysis reveals that the NF-kappa B complex mobilized in tolerant cells is functionally inactive in that NF-kappa B-dependent luciferase constructs containing the human immunodeficiency virus long terminal repeat or the TNF 5'-region show only minimal transactivation after LPS stimulation .", "annotated_text": "Reporter gene analysis reveals that the <protein>NF-kappa B complex</protein> mobilized in <cell_line>tolerant cells</cell_line> is functionally inactive in that <dna>NF-kappa B-dependent luciferase constructs</dna> containing the <dna>human immunodeficiency virus long terminal repeat</dna> or the <dna>TNF 5'-region</dna> show only minimal transactivation after LPS stimulation ."}690{"id": "689", "text": "Similar to Mono Mac 6 cells , primary blood monocytes , when precultured with a low dose of LPS , also become tolerant and produce little TNF after LPS stimulation .", "annotated_text": "Similar to <cell_line>Mono Mac 6 cells</cell_line> , <cell_type>primary blood monocytes</cell_type> , when precultured with a low dose of LPS , also become tolerant and produce little <protein>TNF</protein> after LPS stimulation ."}691{"id": "690", "text": "The tolerant blood monocytes also up-regulate CD14 , and they mobilize NF-kappa B with a predominance of p50 homodimers .", "annotated_text": "The <cell_type>tolerant blood monocytes</cell_type> also up-regulate <protein>CD14</protein> , and they mobilize <protein>NF-kappa B</protein> with a predominance of <protein>p50 homodimers</protein> ."}692{"id": "691", "text": "Taken together , these results demonstrate that tolerance to LPS is determined by post-receptor mechanisms that involve an altered composition of the NF-kappa B complex .", "annotated_text": "Taken together , these results demonstrate that tolerance to LPS is determined by post-receptor mechanisms that involve an altered composition of the <protein>NF-kappa B complex</protein> ."}693{"id": "692", "text": "Analysis of Oct2-isoform expression in lipopolysaccharide-stimulated B lymphocytes .", "annotated_text": "Analysis of <protein>Oct2-isoform</protein> expression in <cell_line>lipopolysaccharide-stimulated B lymphocytes</cell_line> ."}694{"id": "693", "text": "Oct2-isoform expression in splenic B cells stimulated with lipopolysaccharide or lipopolysaccharide plus phorbol-di-butyrate was analysed by cDNA cloning .", "annotated_text": "<protein>Oct2-isoform</protein> expression in <cell_type>splenic B cells</cell_type> stimulated with lipopolysaccharide or lipopolysaccharide plus phorbol-di-butyrate was analysed by cDNA cloning ."}695{"id": "694", "text": "The frequency of Oct2-positive clones was 1/15 , 000 in both libraries .", "annotated_text": "The frequency of <cell_line>Oct2-positive clones</cell_line> was 1/15 , 000 in both libraries ."}696{"id": "695", "text": "Two new isoforms were found that generate novel amino- or carboxy-terminal sequences .", "annotated_text": "Two new isoforms were found that generate novel <protein>amino- or carboxy-terminal sequences</protein> ."}697{"id": "696", "text": "An isoform lacking exon 11 destroyed the carboxy-terminal leucin-zipper region and introduced a frame shift creating a novel , proline-rich carboxy terminus .", "annotated_text": "An isoform lacking <dna>exon 11</dna> destroyed the <protein>carboxy-terminal leucin-zipper region</protein> and introduced a frame shift creating a novel , <protein>proline-rich carboxy terminus</protein> ."}698{"id": "697", "text": "A new exon containing a highly basic region ( 4c ) was characterized , between exons 4 and 5 .", "annotated_text": "A new <dna>exon</dna> containing a highly basic region ( 4c ) was characterized , <dna>between exons 4 and 5</dna> ."}699{"id": "698", "text": "This exon was inserted between glutamine-rich regions 2 and 3 , carboxy terminal of a tentative leucine-zipper structure .", "annotated_text": "This exon was inserted <dna>between glutamine-rich regions 2 and 3</dna> , <protein>carboxy terminal</protein> of a tentative <protein>leucine-zipper structure</protein> ."}700{"id": "699", "text": "In addition , a new combination isoform containing Oct2a 's amino terminal insert ( exon 7a ) and Oct2b 's carboxy terminal insert ( exon 13 ) was found that created a novel large isoform , Oct2ab .", "annotated_text": "In addition , a new combination isoform containing <protein>Oct2a 's amino terminal insert</protein> ( <dna>exon 7a</dna> ) and <protein>Oct2b 's carboxy terminal insert</protein> ( <dna>exon 13</dna> ) was found that created a novel large isoform , <protein>Oct2ab</protein> ."}701{"id": "700", "text": "More frequent use of the classical Oct2a and Oct2b isoforms was observed in the lipopolysaccharide-stimulated B cells , while a preference for the Oct2ab and Oct2ba isoforms was observed in lipopolysaccharide plus phorbol-di-butyrate-treated cells .", "annotated_text": "More frequent use of the classical <protein>Oct2a</protein> and <protein>Oct2b</protein> isoforms was observed in the <cell_line>lipopolysaccharide-stimulated B cells</cell_line> , while a preference for the <protein>Oct2ab</protein> and <protein>Oct2ba</protein> isoforms was observed in <cell_line>lipopolysaccharide plus phorbol-di-butyrate-treated cells</cell_line> ."}702{"id": "701", "text": "Positive regulators of the lineage-specific transcription factor GATA-1 in differentiating erythroid cells .", "annotated_text": "Positive regulators of the lineage-specific <protein>transcription factor</protein> <protein>GATA-1</protein> in <cell_type>differentiating erythroid cells</cell_type> ."}703{"id": "702", "text": "The zinc finger transcription factor GATA-1 is a major regulator of gene expression in erythroid , megakaryocyte , and mast cell lineages .", "annotated_text": "The <protein>zinc finger transcription factor</protein> <protein>GATA-1</protein> is a major regulator of gene expression in <cell_type>erythroid , megakaryocyte , and mast cell lineages</cell_type> ."}704{"id": "703", "text": "GATA-1 binds to WGATAR consensus motifs in the regulatory regions of virtually all erythroid cell-specific genes .", "annotated_text": "<protein>GATA-1</protein> binds to <dna>WGATAR consensus motifs</dna> in the <dna>regulatory regions</dna> of virtually all <dna>erythroid cell-specific genes</dna> ."}705{"id": "704", "text": "Analyses with cultured cells and cell-free systems have provided strong evidence that GATA-1 is involved in control of globin gene expression during erythroid differentiation .", "annotated_text": "Analyses with <cell_line>cultured cells</cell_line> and cell-free systems have provided strong evidence that <protein>GATA-1</protein> is involved in control of <dna>globin gene</dna> expression during erythroid differentiation ."}706{"id": "705", "text": "Targeted mutagenesis of the GATA-1 gene in embryonic stem cells has demonstrated its requirement in normal erythroid development .", "annotated_text": "Targeted mutagenesis of the <dna>GATA-1 gene</dna> in <cell_type>embryonic stem cells</cell_type> has demonstrated its requirement in normal erythroid development ."}707{"id": "706", "text": "Efficient rescue of the defect requires an intact GATA element in the distal promoter , suggesting autoregulatory control of GATA-1 transcription .", "annotated_text": "Efficient rescue of the defect requires an intact <dna>GATA element</dna> in the <dna>distal promoter</dna> , suggesting autoregulatory control of <protein>GATA-1</protein> transcription ."}708{"id": "707", "text": "To examine whether GATA-1 expression involves additional regulatory factors or is maintained entirely by an autoregulatory loop , we have used a transient heterokaryon system to test the ability of erythroid factors to activate the GATA-1 gene in nonerythroid nuclei .", "annotated_text": "To examine whether <protein>GATA-1</protein> expression involves additional <protein>regulatory factors</protein> or is maintained entirely by an autoregulatory loop , we have used a transient heterokaryon system to test the ability of <protein>erythroid factors</protein> to activate the <dna>GATA-1 gene</dna> in nonerythroid nuclei ."}709{"id": "708", "text": "We show here that proerythroblasts and mature erythroid cells contain a diffusible activity ( TAG ) capable of transcriptional activation of GATA-1 and that this activity decreases during the terminal differentiation of erythroid cells .", "annotated_text": "We show here that <cell_type>proerythroblasts</cell_type> and <cell_type>mature erythroid cells</cell_type> contain a diffusible activity ( TAG ) capable of transcriptional activation of <protein>GATA-1</protein> and that this activity decreases during the terminal differentiation of <cell_type>erythroid cells</cell_type> ."}710{"id": "709", "text": "Nuclei from GATA-1 -mutant embryonic stem cells can still be reprogrammed to express their globin genes in erythroid heterokaryons , indicating that de novo induction of GATA-1 is not required for globin gene activation following cell fusion .", "annotated_text": "Nuclei from <cell_line>GATA-1 -mutant embryonic stem cells</cell_line> can still be reprogrammed to express their <dna>globin genes</dna> in <cell_type>erythroid heterokaryons</cell_type> , indicating that de novo induction of <protein>GATA-1</protein> is not required for <dna>globin gene</dna> activation following cell fusion ."}711{"id": "710", "text": "Role of HIV-1 Nef expression in activation pathways in CD4 + T cells .", "annotated_text": "Role of <protein>HIV-1 Nef</protein> expression in activation pathways in <protein>CD4</protein> + T cells ."}712{"id": "711", "text": "The role of the human immunodeficiency virus ( HIV-1 ) Nef protein in T cell activation pathways was investigated using a Jurkat CD4+ cell line stably transfected with a Nef expression vector .", "annotated_text": "The role of the <protein>human immunodeficiency virus ( HIV-1 ) Nef protein</protein> in T cell activation pathways was investigated using a <cell_line>Jurkat CD4+ cell line</cell_line> stably transfected with a Nef expression vector ."}713{"id": "712", "text": "Secretion of IL-2 and TNF-alpha , surface expression of IL-2R , and DNA-binding activity of NF-kappa B and AP-1 ( Fos/Jun ) complex in response to phorbol myristate acetate , TNF-alpha , or immobilized antibodies to CD3 were monitored .", "annotated_text": "Secretion of <protein>IL-2</protein> and <protein>TNF-alpha</protein> , surface expression of <protein>IL-2R</protein> , and DNA-binding activity of <protein>NF-kappa B</protein> and <protein>AP-1 ( Fos/Jun ) complex</protein> in response to phorbol myristate acetate , <protein>TNF-alpha</protein> , or immobilized antibodies to <protein>CD3</protein> were monitored ."}714{"id": "713", "text": "These parameters were not modified by Nef expression in Jurkat cells , whereas stimulation with the same stimuli resulted in partial inhibition of LTR activation in Nef+ Jurkat cells .", "annotated_text": "These parameters were not modified by <protein>Nef</protein> expression in <cell_line>Jurkat cells</cell_line> , whereas stimulation with the same stimuli resulted in partial inhibition of <dna>LTR</dna> activation in <cell_line>Nef+ Jurkat cells</cell_line> ."}715{"id": "714", "text": "This inhibition was not mediated through Nef phosphorylation on Thr-15 or GTP-binding activity because mutations in critical sites did not alter this inhibition .", "annotated_text": "This inhibition was not mediated through <protein>Nef</protein> phosphorylation on Thr-15 or GTP-binding activity because mutations in critical sites did not alter this inhibition ."}716{"id": "715", "text": "Analysis of truncated LTRs confirmed that inhibition of LTR activation was not mediated through NF-kappa B -binding activity but through the region containing the negative responding elements ( NREs ) .", "annotated_text": "Analysis of truncated <dna>LTRs</dna> confirmed that inhibition of <dna>LTR</dna> activation was not mediated through <protein>NF-kappa B</protein> -binding activity but through the region containing the <dna>negative responding elements</dna> ( <dna>NREs</dna> ) ."}717{"id": "716", "text": "These results suggest that Nef downmodulates LTR activation without significantly inhibiting the capacity of T cells to respond to immunological activations .", "annotated_text": "These results suggest that <protein>Nef</protein> downmodulates <dna>LTR</dna> activation without significantly inhibiting the capacity of <cell_type>T cells</cell_type> to respond to immunological activations ."}718{"id": "717", "text": "Tat-binding protein 7 is a subunit of the 26S protease .", "annotated_text": "<protein>Tat-binding protein 7</protein> is a subunit of the <protein>26S protease</protein> ."}719{"id": "718", "text": "Subunit 6 ( S6 ) , an integral component of the 26S protease from human erythrocytes , has been studied by SDS-PAGE , peptide mapping and sequence analysis .", "annotated_text": "<protein>Subunit 6</protein> ( <protein>S6</protein> ) , an integral component of the <protein>26S protease</protein> from <cell_type>human erythrocytes</cell_type> , has been studied by SDS-PAGE , peptide mapping and sequence analysis ."}720{"id": "719", "text": "S6 was cleaved with CNBr and three internal peptides were sequenced .", "annotated_text": "<protein>S6</protein> was cleaved with <protein>CNBr</protein> and three internal peptides were sequenced ."}721{"id": "720", "text": "A comparison with known proteins in Genbank revealed that all three S6 peptides match the predicted sequence of TBP7 , Tat-binding protein 7 .", "annotated_text": "A comparison with known proteins in Genbank revealed that all three <protein>S6</protein> peptides match the predicted sequence of <protein>TBP7</protein> , <protein>Tat-binding protein 7</protein> ."}722{"id": "721", "text": "Based on peptide matches covering more than 10 % of the TBP7 sequence , and the fact that the migration of S6 on SDS-PAGE is consistent with the estimated molecular mass for TBP7 , we conclude that subunit 6 of the 26S protease is TBP7 .", "annotated_text": "Based on peptide matches covering more than 10 % of the <protein>TBP7</protein> sequence , and the fact that the migration of <protein>S6</protein> on SDS-PAGE is consistent with the estimated molecular mass for <protein>TBP7</protein> , we conclude that <protein>subunit 6</protein> of the <protein>26S protease</protein> is <protein>TBP7</protein> ."}723{"id": "722", "text": "Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues .", "annotated_text": "Hypoxia causes the activation of <protein>nuclear factor kappa B</protein> through the phosphorylation of <protein>I kappa B alpha</protein> on tyrosine residues ."}724{"id": "723", "text": "The response of mammalian cells to stress is controlled by transcriptional regulatory proteins such as nuclear factor kappa B ( NF-kappa B ) to induce a wide variety of early response genes .", "annotated_text": "The response of <cell_type>mammalian cells</cell_type> to stress is controlled by <protein>transcriptional regulatory proteins</protein> such as <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) to induce a wide variety of <dna>early response genes</dna> ."}725{"id": "724", "text": "In this report , we show that exposure of cells to hypoxia ( 0.02 % O2 ) results in I kappa B alpha degradation , increased NF-kappa B DNA binding activity , and transactivation of a reporter gene construct containing two NF-kappa B DNA binding sites .", "annotated_text": "In this report , we show that exposure of cells to hypoxia ( 0.02 % O2 ) results in <protein>I kappa B alpha</protein> degradation , increased <protein>NF-kappa B</protein> DNA binding activity , and transactivation of a <dna>reporter gene construct</dna> containing two <dna>NF-kappa B DNA binding sites</dna> ."}726{"id": "725", "text": "Pretreatment of cells with protein tyrosine kinase inhibitors and the dominant negative allele of c-Raf-1 ( Raf 301 ) inhibited I kappa B alpha degradation , NF-kappa B binding , and transactivation of kappa B reporter constructs by hypoxia .", "annotated_text": "Pretreatment of cells with protein <protein>tyrosine kinase</protein> inhibitors and the <dna>dominant negative allele</dna> of <dna>c-Raf-1</dna> ( <protein>Raf 301</protein> ) inhibited <protein>I kappa B alpha</protein> degradation , <protein>NF-kappa B</protein> binding , and transactivation of <dna>kappa B reporter constructs</dna> by hypoxia ."}727{"id": "726", "text": "To demonstrate a direct link between changes in the phosphorylation pattern of I kappa B alpha with NF-kappa B activation , we immunoprecipitated I kappa B alpha after varying times of hypoxic exposure and found that its tyrosine phosphorylation status increased during hypoxic exposure .", "annotated_text": "To demonstrate a direct link between changes in the phosphorylation pattern of <protein>I kappa B alpha</protein> with <protein>NF-kappa B</protein> activation , we immunoprecipitated <protein>I kappa B alpha</protein> after varying times of hypoxic exposure and found that its tyrosine phosphorylation status increased during hypoxic exposure ."}728{"id": "727", "text": "Inhibition of the transfer of tyrosine phosphoryl groups onto I kappa B alpha prevented I kappa B alpha degradation and NF-kappa B binding .", "annotated_text": "Inhibition of the transfer of tyrosine phosphoryl groups onto <protein>I kappa B alpha</protein> prevented <protein>I kappa B alpha</protein> degradation and <protein>NF-kappa B</protein> binding ."}729{"id": "728", "text": "In comparison to other activators of NF-kappa B such as phorbol myristate acetate or tumor necrosis factor , we did not detect changes in the tyrosine phosphorylation status of I kappa B alpha following treatment with either of these agents .", "annotated_text": "In comparison to other activators of <protein>NF-kappa B</protein> such as phorbol myristate acetate or <protein>tumor necrosis factor</protein> , we did not detect changes in the tyrosine phosphorylation status of <protein>I kappa B alpha</protein> following treatment with either of these agents ."}730{"id": "729", "text": "These results suggest that tyrosine phosphorylation of I kappa B alpha during hypoxia is an important proximal step which precedes its dissociation and degradation from NF-kappa B .", "annotated_text": "These results suggest that tyrosine phosphorylation of <protein>I kappa B alpha</protein> during hypoxia is an important proximal step which precedes its dissociation and degradation from <protein>NF-kappa B</protein> ."}731{"id": "730", "text": "Overproduction of NFKB2 ( lyt-10 ) and c-Rel : a mechanism for HTLV-I Tax -mediated trans-activation via the NF-kappa B signalling pathway .", "annotated_text": "Overproduction of <protein>NFKB2</protein> ( <protein>lyt-10</protein> ) and <protein>c-Rel</protein> : a mechanism for <protein>HTLV-I Tax</protein> -mediated trans-activation via the <protein>NF-kappa B</protein> signalling pathway ."}732{"id": "731", "text": "Molecular , biochemical and epidemiological evidence implicate HTLV-I as an etiologic agent of adult T cell leukemia ( ATL ) .", "annotated_text": "Molecular , biochemical and epidemiological evidence implicate HTLV-I as an etiologic agent of adult T cell leukemia ( ATL ) ."}733{"id": "732", "text": "The Tax protein of HTLV-I , a positive transcriptional activator of HTLV-I gene expression , is a viral oncogene that also increases transcription of cellular genes including GM-CSF , IL-2R alpha and IL-2 .", "annotated_text": "The <protein>Tax protein</protein> of HTLV-I , a <protein>positive transcriptional activator</protein> of HTLV-I gene expression , is a viral oncogene that also increases transcription of <dna>cellular genes</dna> including <protein>GM-CSF</protein> , <protein>IL-2R alpha</protein> and <protein>IL-2</protein> ."}734{"id": "733", "text": "One of the cellular targets of the trans-activating effects of Tax is the NF-kappa B/Rel family of transcription factors , pleiotropic regulators of immunoregulatory , cytokine and viral gene expression .", "annotated_text": "One of the cellular targets of the trans-activating effects of Tax is the <protein>NF-kappa B/Rel family</protein> of <protein>transcription factors</protein> , <protein>pleiotropic regulators</protein> of immunoregulatory , cytokine and viral gene expression ."}735{"id": "734", "text": "In this report , we demonstrate that NFKB2 ( lyt-10 ) and c-Rel are overexpressed in HTLV-I infected and Tax-expressing cells and , together , account for the majority of the constitutive NF-kappa B binding activity in these cells before and after PMA stimulation .", "annotated_text": "In this report , we demonstrate that <protein>NFKB2</protein> ( <protein>lyt-10</protein> ) and <protein>c-Rel</protein> are overexpressed in HTLV-I infected and <cell_type>Tax-expressing cells</cell_type> and , together , account for the majority of the constitutive <protein>NF-kappa B</protein> binding activity in these cells before and after PMA stimulation ."}736{"id": "735", "text": "Most importantly , we show a Tax -dependent correlation between expression of NFKB2 ( p100 ) and processing to the DNA binding NFKB2 ( p52 ) form , induction of c-Rel , and trans-activation of NF-kappa B -mediated gene expression .", "annotated_text": "Most importantly , we show a <protein>Tax</protein> -dependent correlation between expression of <protein>NFKB2</protein> ( <protein>p100</protein> ) and processing to the DNA binding <protein>NFKB2</protein> ( <protein>p52</protein> ) form , induction of <protein>c-Rel</protein> , and trans-activation of <protein>NF-kappa B</protein> -mediated gene expression ."}737{"id": "736", "text": "Furthermore , the NFKB2 precursor is physically associated with c-Rel and with Tax in HTLV-I infected cells .", "annotated_text": "Furthermore , the <protein>NFKB2</protein> precursor is physically associated with <protein>c-Rel</protein> and with <protein>Tax</protein> in <cell_type>HTLV-I infected cells</cell_type> ."}738{"id": "737", "text": "We propose that NFKB2 synthesis and processing allows continuous nuclear expression of an otherwise cytoplasmic protein and , in conjunction with overexpression of c-Rel , NFKB2 alters the NF-kappa B signalling pathway and contributes to leukemic transformation of T cells by HTLV-I .", "annotated_text": "We propose that <protein>NFKB2</protein> synthesis and processing allows continuous nuclear expression of an otherwise <protein>cytoplasmic protein</protein> and , in conjunction with overexpression of <protein>c-Rel</protein> , <protein>NFKB2</protein> alters the <protein>NF-kappa B</protein> signalling pathway and contributes to leukemic transformation of <cell_type>T cells</cell_type> by HTLV-I ."}739{"id": "738", "text": "Retinoic acid downmodulates erythroid differentiation and GATA1 expression in purified adult-progenitor culture .", "annotated_text": "Retinoic acid downmodulates erythroid differentiation and <protein>GATA1</protein> expression in <cell_line>purified adult-progenitor culture</cell_line> ."}740{"id": "739", "text": "All-trans retinoic acid ( RA ) is an important morphogen in vertebrate development , a normal constituent in human adult blood and is also involved in the control of cell growth and differentiation in acute promyelocytic leukemia .", "annotated_text": "All-trans retinoic acid ( RA ) is an important morphogen in vertebrate development , a normal constituent in human adult blood and is also involved in the control of cell growth and differentiation in acute promyelocytic leukemia ."}741{"id": "740", "text": "We have examined the effects of RA on normal hematopoiesis by using early hematopoietic progenitor cells ( HPC ) stringently purified from adult peripheral blood .", "annotated_text": "We have examined the effects of RA on normal hematopoiesis by using early <cell_type>hematopoietic progenitor cells</cell_type> ( <cell_type>HPC</cell_type> ) stringently purified from adult peripheral blood ."}742{"id": "741", "text": "In clonogenetic fetal calf serum-supplemented ( FCS+ ) or -nonsupplemented ( FCS- ) culture treated with saturating levels of interleukin-3 ( IL-3 ) granulocyte-macrophage colony-stimulating factor ( GM-CSF ) and erythropoietin ( Ep ) ( combined with c-kit ligand in FCS ( - ) -culture conditions ) , RA induces a dramatic dose-dependent shift from erythroid to granulomonocytic colony formation , the latter colonies being essentially represented by granulocytic clones .", "annotated_text": "In <cell_line>clonogenetic fetal calf serum-supplemented ( FCS+ ) or -nonsupplemented ( FCS- ) culture</cell_line> treated with saturating levels of <protein>interleukin-3</protein> ( <protein>IL-3</protein> ) <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) and <protein>erythropoietin</protein> ( <protein>Ep</protein> ) ( combined with <protein>c-kit</protein> ligand in FCS ( - ) -culture conditions ) , RA induces a dramatic dose-dependent shift from erythroid to granulomonocytic colony formation , the latter colonies being essentially represented by <cell_line>granulocytic clones</cell_line> ."}743{"id": "742", "text": "This shift is apparently not caused by a recruitment phenomenon , because in FCS+ culture , the total number of colonies is not significantly modified by RA addition .", "annotated_text": "This shift is apparently not caused by a recruitment phenomenon , because in <cell_line>FCS+ culture</cell_line> , the total number of colonies is not significantly modified by RA addition ."}744{"id": "743", "text": "In FCS- liquid-suspension culture supplemented with saturating Ep level and low-dose IL-3/GM-CSF , adult HPC undergo unilineage erythropoietic differentiation : Here again , treatment with high-dose RA induces a shift from the erythroid to granulocytic differentiation pathway .", "annotated_text": "In <cell_line>FCS- liquid-suspension culture</cell_line> supplemented with saturating <protein>Ep</protein> level and <protein>low-dose IL-3/GM-CSF</protein> , adult <cell_type>HPC</cell_type> undergo unilineage erythropoietic differentiation : Here again , treatment with high-dose RA induces a shift from the erythroid to granulocytic differentiation pathway ."}745{"id": "744", "text": "Studies on RA time-response or pulse treatment in semisolid or liquid culture show that early RA addition is most effective , thus indicating that early but not late HPC are sensitive to its action .", "annotated_text": "Studies on RA time-response or pulse treatment in semisolid or liquid culture show that early RA addition is most effective , thus indicating that early but not late <cell_type>HPC</cell_type> are sensitive to its action ."}746{"id": "745", "text": "We then analyzed the expression of the master GATA1 gene , which encodes a finger transcription factor required for normal erythroid development ; addition of RA to HPC stimulated into unilineage erythropoietic differentiation in liquid culture caused a virtually complete inhibition of GATA1 mRNA induction .", "annotated_text": "We then analyzed the expression of the <dna>master GATA1 gene</dna> , which encodes a <protein>finger transcription factor</protein> required for normal erythroid development ; addition of RA to <cell_type>HPC</cell_type> stimulated into unilineage erythropoietic differentiation in liquid culture caused a virtually complete inhibition of <rna>GATA1 mRNA</rna> induction ."}747{"id": "746", "text": "These results indicate that RA directly inhibits the erythroid differentiation program at the level of early adult HPC , and may lead to a shift from the erythroid to granulocytic differentiation pathway .", "annotated_text": "These results indicate that RA directly inhibits the erythroid differentiation program at the level of early adult <cell_type>HPC</cell_type> , and may lead to a shift from the erythroid to granulocytic differentiation pathway ."}748{"id": "747", "text": "This phenomenon is correlated with inhibition of GATA1 induction in the early stages of erythropoietic differentiation .", "annotated_text": "This phenomenon is correlated with inhibition of <protein>GATA1</protein> induction in the early stages of erythropoietic differentiation ."}749{"id": "748", "text": "Induction of phosphatidylinositol turnover and EGR-1 mRNA expression by crosslinking of surface IgM and IgD in the human B cell line B104 .", "annotated_text": "Induction of phosphatidylinositol turnover and <rna>EGR-1 mRNA</rna> expression by crosslinking of surface <protein>IgM</protein> and <protein>IgD</protein> in the <cell_line>human B cell line B104</cell_line> ."}750{"id": "749", "text": "We have previously shown that a human B lymphoma cell line , B104 , expressed surface IgM ( sIgM ) and surface IgD ( sIgD ) , and that crosslinking of sIgM and sIgD by anti-IgM antibody ( Ab ) and anti-IgD Ab , respectively , induced Ca2+ influx to almost the same degree , whereas only sIgM -crosslinking caused B104 cell death .", "annotated_text": "We have previously shown that a <cell_line>human B lymphoma cell line , B104</cell_line> , expressed <protein>surface IgM</protein> ( <protein>sIgM</protein> ) and <protein>surface IgD</protein> ( <protein>sIgD</protein> ) , and that crosslinking of <protein>sIgM</protein> and <protein>sIgD</protein> by <protein>anti-IgM antibody ( Ab )</protein> and <protein>anti-IgD Ab</protein> , respectively , induced Ca2+ influx to almost the same degree , whereas only <protein>sIgM</protein> -crosslinking caused <cell_line>B104 cell</cell_line> death ."}751{"id": "750", "text": "Here , we investigated the accumulation of cyclic AMP ( cAMP ) , the hydrolysis of inositol phosphates , protein kinase C ( PKC ) activity and the induction of Egr-1 and c-fos mRNA expression by sIgM- and sIgD-crosslinking to examine differences in the signals mediated through sIgM and sIgD in B104 cells .", "annotated_text": "Here , we investigated the accumulation of cyclic AMP ( cAMP ) , the hydrolysis of inositol phosphates , <protein>protein kinase C</protein> ( <protein>PKC</protein> ) activity and the induction of Egr-1 and c-fos mRNA expression by sIgM- and sIgD-crosslinking to examine differences in the signals mediated through <protein>sIgM</protein> and <protein>sIgD</protein> in <cell_line>B104 cells</cell_line> ."}752{"id": "751", "text": "Both sIgM- and sIgD-crosslinking with antibodies induced elevation of cAMP levels , phosphatidylinositol turnover , PKC activation and expression of Egr-1 and c-fos mRNA , although sIgM -crosslinking was more effective than sIgD -crosslinking , presumably due to the higher expression of sIgM than of sIgD .", "annotated_text": "Both sIgM- and sIgD-crosslinking with antibodies induced elevation of cAMP levels , phosphatidylinositol turnover , <protein>PKC</protein> activation and expression of <rna>Egr-1 and c-fos mRNA</rna> , although <protein>sIgM</protein> -crosslinking was more effective than <protein>sIgD</protein> -crosslinking , presumably due to the higher expression of <protein>sIgM</protein> than of <protein>sIgD</protein> ."}753{"id": "752", "text": "Egr-1 mRNA expression induced by sIgM- and sIgD-crosslinking was inhibited by H7 , erbstatin and genistein , but not by HA1004 .", "annotated_text": "<rna>Egr-1 mRNA</rna> expression induced by sIgM- and sIgD-crosslinking was inhibited by <protein>H7</protein> , erbstatin and genistein , but not by HA1004 ."}754{"id": "753", "text": "Erbstatin and genistein inhibited the sIg-crosslinking-induced Egr-1 mRNA expression in a dose-dependent manner parallel to that observed in the inhibition of sIg-crosslinking-induced protein tyrosine phosphorylation .", "annotated_text": "Erbstatin and genistein inhibited the sIg-crosslinking-induced <rna>Egr-1 mRNA</rna> expression in a dose-dependent manner parallel to that observed in the inhibition of sIg-crosslinking-induced protein tyrosine phosphorylation ."}755{"id": "754", "text": "Phorbol myristate acetate induced Egr-1 mRNA expression but forskolin and dibutyryl cyclic AMP did not .", "annotated_text": "Phorbol myristate acetate induced <rna>Egr-1 mRNA</rna> expression but forskolin and dibutyryl cyclic AMP did not ."}756{"id": "755", "text": "These findings suggest that the Egr-1 mRNA activating signals through sIgM and sIgD are protein tyrosine kinase- and PKC-dependent , but protein kinase A -independent .", "annotated_text": "These findings suggest that the <rna>Egr-1 mRNA</rna> activating signals through <protein>sIgM</protein> and <protein>sIgD</protein> are protein tyrosine kinase- and PKC-dependent , but <protein>protein kinase A</protein> -independent ."}757{"id": "756", "text": "Cyclosporin A ( CsA ) and FK506 rescued B104 cells from death induced by anti-IgM Ab , but did not affect the expression of Egr-1 and c-fos mRNA , showing that CsA and FK506 affect signal transducers differently from or downstream to these molecules .", "annotated_text": "Cyclosporin A ( CsA ) and FK506 rescued <cell_line>B104 cells</cell_line> from death induced by <protein>anti-IgM Ab</protein> , but did not affect the expression of <protein>Egr-1</protein> and <rna>c-fos mRNA</rna> , showing that CsA and FK506 affect signal transducers differently from or downstream to these molecules ."}758{"id": "757", "text": "The difference in signals transduced through sIgM and sIgD in B104 cells is discussed .", "annotated_text": "The difference in signals transduced through <protein>sIgM</protein> and <protein>sIgD</protein> in <cell_line>B104 cells</cell_line> is discussed ."}759{"id": "758", "text": "Direct exposure to 2 , 3 , 7 , 8-tetrachlorodibenzo-p-dioxin ( TCDD ) increases infectivity of human erythrocytes to a malarial parasite .", "annotated_text": "Direct exposure to 2 , 3 , 7 , 8-tetrachlorodibenzo-p-dioxin ( TCDD ) increases infectivity of <cell_type>human erythrocytes</cell_type> to a malarial parasite ."}760{"id": "759", "text": "Direct exposure to 10 nM 2 , 3 , 7 , 8-TCDD caused a 75 % increase and a 2-fold increase in the infectivity of isolated human erythrocytes to P. falciparum after 48 hours when the parasites were in an unsynchronized or synchronized state of growth , respectively .", "annotated_text": "Direct exposure to 10 nM 2 , 3 , 7 , 8-TCDD caused a 75 % increase and a 2-fold increase in the infectivity of isolated <cell_type>human erythrocytes</cell_type> to P. falciparum after 48 hours when the parasites were in an unsynchronized or synchronized state of growth , respectively ."}761{"id": "760", "text": "Treatment of human erythrocytes with 10 microM sodium orthovanadate ( NaOV ) , an inhibitor of plasma membrane Ca-ATPase and phosphotyrosine phosphatase , decreased parasitemia by 30 % .", "annotated_text": "Treatment of <cell_type>human erythrocytes</cell_type> with 10 microM sodium orthovanadate ( NaOV ) , an inhibitor of <protein>plasma membrane Ca-ATPase</protein> and <protein>phosphotyrosine phosphatase</protein> , decreased parasitemia by 30 % ."}762{"id": "761", "text": "Co-treatment of RBCs with TCDD and NaOV completely blocked the TCDD-induced increase in parasitemia .", "annotated_text": "Co-treatment of <cell_type>RBCs</cell_type> with TCDD and NaOV completely blocked the TCDD-induced increase in parasitemia ."}763{"id": "762", "text": "Because erythrocytes are anucleated , these results are discussed as evidence for biochemical changes by TCDD without requiring the activation of gene products .", "annotated_text": "Because <cell_type>erythrocytes</cell_type> are anucleated , these results are discussed as evidence for biochemical changes by TCDD without requiring the activation of <protein>gene products</protein> ."}764{"id": "763", "text": "Evidence for a trans-acting activator function regulating the expression of the human CD5 antigen .", "annotated_text": "Evidence for a <protein>trans-acting activator</protein> function regulating the expression of the <protein>human CD5 antigen</protein> ."}765{"id": "764", "text": "Interspecies somatic cell hybrids were generated by fusing the mouse T-lymphoma cell line , BW5147 , with normal human T lymphocytes at different stages of differentiation .", "annotated_text": "Interspecies <cell_line>somatic cell hybrids</cell_line> were generated by fusing the <cell_line>mouse T-lymphoma cell line</cell_line> , <cell_line>BW5147</cell_line> , with <cell_type>normal human T lymphocytes</cell_type> at different stages of differentiation ."}766{"id": "765", "text": "Thymocytes , activated peripheral T lymphocytes , or an activated T-cell clone were used as human partners , respectively , in three independent fusions .", "annotated_text": "<cell_type>Thymocytes</cell_type> , <cell_type>activated peripheral T lymphocytes</cell_type> , or an <cell_line>activated T-cell clone</cell_line> were used as human partners , respectively , in three independent fusions ."}767{"id": "766", "text": "Irrespective of the human cell partner used for fusion , a certain number of hybrids lost CD5 surface expression over a period of time in culture .", "annotated_text": "Irrespective of the human cell partner used for fusion , a certain number of <cell_line>hybrids</cell_line> lost <protein>CD5</protein> surface expression over a period of time in culture ."}768{"id": "767", "text": "Analysis at the phenotype and genetic level showed that lack of CD5 expression was due neither to segregation of human autosome 11 , on which the CD5 gene has been mapped , nor to deletion of the CD5 structural gene .", "annotated_text": "Analysis at the phenotype and genetic level showed that lack of <protein>CD5</protein> expression was due neither to segregation of <dna>human autosome 11</dna> , on which the <dna>CD5 gene</dna> has been mapped , nor to deletion of the <dna>CD5 structural gene</dna> ."}769{"id": "768", "text": "Furthermore , loss of CD5 surface expression correlated with the absence of specific mRNA .", "annotated_text": "Furthermore , loss of <protein>CD5</protein> surface expression correlated with the absence of specific <rna>mRNA</rna> ."}770{"id": "769", "text": "Since these hybrids preferentially segregate human chromosomes , these results indicate the existence of a non-syntenic trans-active locus , or loci , positively controlling the expression of the human CD5 gene .", "annotated_text": "Since these hybrids preferentially segregate human chromosomes , these results indicate the existence of a <dna>non-syntenic trans-active locus</dna> , or loci , positively controlling the expression of the <dna>human CD5 gene</dna> ."}771{"id": "770", "text": "Induction of the CD11b gene during activation of the monocytic cell line U937 requires a novel nuclear factor MS-2 [ published erratum appears in J Immunol 1999 Jul 15 ; 163 ( 2 ) : 1091 ]", "annotated_text": "Induction of the <dna>CD11b gene</dna> during activation of the <cell_line>monocytic cell line U937</cell_line> requires a novel <protein>nuclear factor</protein> <protein>MS-2</protein> [ published erratum appears in J Immunol 1999 Jul 15 ; 163 ( 2 ) : 1091 ]"}772{"id": "771", "text": "The differentiation of myeloid precursors into mature myelomonocytic cells is characterized by the induction of the gene encoding the beta2 integrin CD11b .", "annotated_text": "The differentiation of <cell_type>myeloid precursors</cell_type> into mature <cell_type>myelomonocytic cells</cell_type> is characterized by the induction of the gene encoding the <protein>beta2 integrin</protein> <protein>CD11b</protein> ."}773{"id": "772", "text": "The transcription factors Sp1 and PU.1 prime the CD11b promoter , but the nature of the factors responsible for its inducible expression are unknown .", "annotated_text": "The <protein>transcription factors</protein> <protein>Sp1</protein> and <protein>PU.1 prime</protein> the <dna>CD11b promoter</dna> , but the nature of the factors responsible for its inducible expression are unknown ."}774{"id": "773", "text": "In addition to the CD11b gene , the homologous genes encoding CD11a and CD11c also exhibit inducible expression during myeloid differentiation .", "annotated_text": "In addition to the <dna>CD11b gene</dna> , the homologous genes encoding <protein>CD11a</protein> and <protein>CD11c</protein> also exhibit inducible expression during myeloid differentiation ."}775{"id": "774", "text": "Therefore , we compared the nucleotide sequences of the CD11a , CD11b , and CD11c gene promoters to identify common elements that might contribute to inducible expression .", "annotated_text": "Therefore , we compared the <dna>nucleotide sequences</dna> of the <dna>CD11a , CD11b , and CD11c gene promoters</dna> to identify common elements that might contribute to inducible expression ."}776{"id": "775", "text": "This analysis identified one such element repeated four times within the CD11b promoter .", "annotated_text": "This analysis identified one such element repeated four times within the <dna>CD11b promoter</dna> ."}777{"id": "776", "text": "Mutation of these elements indicated that two , MS-2beta and MS-2gamma , are critical to the induction of the CD11b gene during differentiation of the pro-monocytic cell line U937 .", "annotated_text": "Mutation of these elements indicated that two , <protein>MS-2beta</protein> and <protein>MS-2gamma</protein> , are critical to the induction of the <dna>CD11b gene</dna> during differentiation of the <cell_line>pro-monocytic cell line U937</cell_line> ."}778{"id": "777", "text": "Electrophoretic mobility shift assays indicate that MS-2beta and MS-2gamma interact with nuclear factors that are induced during U937 differentiation .", "annotated_text": "Electrophoretic mobility shift assays indicate that <protein>MS-2beta</protein> and <protein>MS-2gamma</protein> interact with <protein>nuclear factors</protein> that are induced during <cell_line>U937</cell_line> differentiation ."}779{"id": "778", "text": "These factors are detected at the time the CD11b promoter is activated .", "annotated_text": "These factors are detected at the time the <dna>CD11b promoter</dna> is activated ."}780{"id": "779", "text": "The molecular mass of these factors is approximately 28 kDa , and their DNA binding characteristics are indistinguishable from those of the novel nuclear factor MS-2 .", "annotated_text": "The molecular mass of these factors is approximately 28 kDa , and their DNA binding characteristics are indistinguishable from those of the novel <protein>nuclear factor</protein> <protein>MS-2</protein> ."}781{"id": "780", "text": "Taken together , our data indicate that MS-2 mediates induction of the CD11b gene as cells of the monocytic lineage mature .", "annotated_text": "Taken together , our data indicate that <protein>MS-2</protein> mediates induction of the <dna>CD11b gene</dna> as cells of the monocytic lineage mature ."}782{"id": "781", "text": "The presence of multiple potential binding sites for MS-2 in the promoter regions of a wide range of genes expressed in mature myeloid cells suggests this factor plays a general role in myeloid differentiation .", "annotated_text": "The presence of multiple potential binding sites for <protein>MS-2</protein> in the promoter regions of a wide range of genes expressed in <cell_type>mature myeloid cells</cell_type> suggests this factor plays a general role in myeloid differentiation ."}783{"id": "782", "text": "Acetylsalicylic acid and sodium salicylate inhibit LPS-induced NF-kappa B/c-Rel nuclear translocation , and synthesis of tissue factor ( TF ) and tumor necrosis factor alfa ( TNF-alpha ) in human monocytes .", "annotated_text": "Acetylsalicylic acid and sodium salicylate inhibit LPS-induced <protein>NF-kappa B/c-Rel</protein> nuclear translocation , and synthesis of <protein>tissue factor</protein> ( <protein>TF</protein> ) and <protein>tumor necrosis factor alfa</protein> ( <protein>TNF-alpha</protein> ) in <cell_type>human monocytes</cell_type> ."}784{"id": "783", "text": "We have investigated the effects of acetylsalicylic acid and sodium salicylate on the LPS-induced synthesis of the pro-coagulant protein tissue factor ( TF ) and the pro-inflammatory protein tumor necrosis factor-alpha ( TNF-alpha ) , as well as the prostaglandin PGE2 in human monocytes .", "annotated_text": "We have investigated the effects of acetylsalicylic acid and sodium salicylate on the LPS-induced synthesis of the pro-coagulant protein tissue factor ( TF ) and the pro-inflammatory protein tumor necrosis factor-alpha ( <protein>TNF-alpha</protein> ) , as well as the <protein>prostaglandin PGE2</protein> in <cell_type>human monocytes</cell_type> ."}785{"id": "784", "text": "Both drugs dose-dependently inhibited LPS-induced TF and TNF-alpha synthesis at the mRNA and the protein level , and reduced PGE2 production .", "annotated_text": "Both drugs dose-dependently inhibited <protein>LPS-induced TF</protein> and <protein>TNF-alpha</protein> synthesis at the <rna>mRNA</rna> and the protein level , and reduced <protein>PGE2</protein> production ."}786{"id": "785", "text": "As evidenced by electro mobility shift assay ( EMSA ) and the use of a NF-kappa B prototypic probe , these drugs probably exert their inhibitory effects by interference with the nuclear translocation of NF-kappa B/c-Rel proteins .", "annotated_text": "As evidenced by electro mobility shift assay ( EMSA ) and the use of a <dna>NF-kappa B prototypic probe</dna> , these drugs probably exert their inhibitory effects by interference with the nuclear translocation of <protein>NF-kappa B/c-Rel proteins</protein> ."}787{"id": "786", "text": "These data may expand the understanding of the anti-thrombotic and anti-inflammatory effects of these drugs when activation of monocytes occurs .", "annotated_text": "These data may expand the understanding of the anti-thrombotic and anti-inflammatory effects of these drugs when activation of <cell_type>monocytes</cell_type> occurs ."}788{"id": "787", "text": "Interferon augments PML and PML/RAR alpha expression in normal myeloid and acute promyelocytic cells and cooperates with all-trans retinoic acid to induce maturation of a retinoid-resistant promyelocytic cell line .", "annotated_text": "Interferon augments <protein>PML</protein> and <protein>PML/RAR alpha</protein> expression in normal <cell_type>myeloid</cell_type> and <cell_type>acute promyelocytic cells</cell_type> and cooperates with all-trans retinoic acid to induce maturation of a <cell_line>retinoid-resistant promyelocytic cell line</cell_line> ."}789{"id": "788", "text": "The PML gene is fused to the retinoic acid receptor alpha gene ( RAR alpha ) in the acute promyelocytic leukemia ( APL ) 15 ; 17 translocation .", "annotated_text": "The <dna>PML gene</dna> is fused to the <dna>retinoic acid receptor alpha gene</dna> ( <dna>RAR alpha</dna> ) in the acute promyelocytic leukemia ( APL ) 15 ; 17 translocation ."}790{"id": "789", "text": "PML is expressed in diverse tissues and cell lines and localized in the nucleus with a typical speckled pattern .", "annotated_text": "<protein>PML</protein> is expressed in diverse tissues and cell lines and localized in the nucleus with a typical speckled pattern ."}791{"id": "790", "text": "In the bone marrow , it is preferentially expressed in myeloid cells .", "annotated_text": "In the bone marrow , it is preferentially expressed in <cell_type>myeloid cells</cell_type> ."}792{"id": "791", "text": "PML appears to be transcriptionally regulated by class I and II interferons , which raises the possibility that interferons modulate the function and growth and differentiation potential of normal myeloid cells and precursors by activating PML -dependent pathways .", "annotated_text": "<protein>PML</protein> appears to be transcriptionally regulated by <protein>class I and II interferons</protein> , which raises the possibility that interferons modulate the function and growth and differentiation potential of normal <cell_type>myeloid cells</cell_type> and precursors by activating <protein>PML</protein> -dependent pathways ."}793{"id": "792", "text": "Similarly , interferons could act on APL cells , alone or in combination with all-trans retinoic acid ( RA ) , especially if the PML/RAR alpha fusion transcript that results from the t ( 15 ; 17 ) is induced by interferon .", "annotated_text": "Similarly , interferons could act on <cell_type>APL cells</cell_type> , alone or in combination with all-trans retinoic acid ( RA ) , especially if the <rna>PML/RAR alpha fusion transcript</rna> that results from the <dna>t ( 15 ; 17 )</dna> is induced by <protein>interferon</protein> ."}794{"id": "793", "text": "We report here that PML is expressed at low levels or not expressed in normal circulating human monocytes , lymphocytes , and polymorphonucleate cells , but is markedly induced by interferon ; that PML and PML/RAR alpha expression is augmented by interferon in the NB4 APL cell line , which carries the t ( 15 ; 17 ) , and in APL blasts from patients ; that interferon inhibits growth and survival of NB4 APL cells in cooperation with RA ; that interferons alone have minimal maturation effect on NB4 cells ; and , finally , that interferon gamma , but not alpha or beta , induces maturation and growth suppression of NB4 cells with de novo retinoid resistance , and partially restores RA response .", "annotated_text": "We report here that <protein>PML</protein> is expressed at low levels or not expressed in normal circulating <cell_type>human monocytes</cell_type> , <cell_type>lymphocytes</cell_type> , and <cell_type>polymorphonucleate cells</cell_type> , but is markedly induced by <protein>interferon</protein> ; that <protein>PML</protein> and <protein>PML/RAR alpha</protein> expression is augmented by <protein>interferon</protein> in the <cell_line>NB4 APL cell line</cell_line> , which carries the <dna>t ( 15 ; 17 )</dna> , and in <cell_type>APL blasts</cell_type> from patients ; that <protein>interferon</protein> inhibits growth and survival of NB4 <cell_type>APL cells</cell_type> in cooperation with RA ; that interferons alone have minimal maturation effect on <cell_line>NB4 cells</cell_line> ; and , finally , that <protein>interferon gamma , but not alpha or beta</protein> , induces maturation and growth suppression of <cell_line>NB4 cells</cell_line> with de novo retinoid resistance , and partially restores RA response ."}795{"id": "794", "text": "Effects of Ara-C on neutral sphingomyelinase and mitogen- and stress- activated protein kinases in T-lymphocyte cell lines .", "annotated_text": "Effects of Ara-C on <protein>neutral sphingomyelinase</protein> and <protein>mitogen- and stress- activated protein kinases</protein> in <cell_line>T-lymphocyte cell lines</cell_line> ."}796{"id": "795", "text": "Neutral sphingomyelinase ( SMase ) can be activated by extracellular signals to produce ceramide , which may affect mitogen-activated protein kinase ( MAPK ) activities .", "annotated_text": "<protein>Neutral sphingomyelinase</protein> ( <protein>SMase</protein> ) can be activated by extracellular signals to produce ceramide , which may affect <protein>mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) activities ."}797{"id": "796", "text": "Neutral SMase activity was assessed in membranes from Jurkat , a human T-cell line , and EL4 , a murine T-cell line .", "annotated_text": "Neutral <protein>SMase</protein> activity was assessed in membranes from <cell_line>Jurkat</cell_line> , a <cell_line>human T-cell line</cell_line> , and <cell_line>EL4</cell_line> , a <cell_line>murine T-cell line</cell_line> ."}798{"id": "797", "text": "Ara-C activated SMase with 10 minutes in both Jurkat and EL4 cells , while phorbol ester ( PMA ) had no effect .", "annotated_text": "Ara-C activated <protein>SMase</protein> with 10 minutes in both Jurkat and <cell_line>EL4 cells</cell_line> , while phorbol ester ( PMA ) had no effect ."}799{"id": "798", "text": "PMA , but not Ara-C or ceramides , activated ERK MAPKS , in Jurkat and EL4 .", "annotated_text": "PMA , but not Ara-C or ceramides , activated <protein>ERK MAPKS</protein> , in <cell_line>Jurkat</cell_line> and <cell_line>EL4</cell_line> ."}800{"id": "799", "text": "PMA acted synergistically with ionomycin to activate JNK MAPKs in Jurkat and EL4 within 10 minutes .", "annotated_text": "PMA acted synergistically with ionomycin to activate <protein>JNK MAPKs</protein> in <cell_line>Jurkat</cell_line> and <cell_line>EL4</cell_line> within 10 minutes ."}801{"id": "800", "text": "Ara-C activated JNKs only after prolonged incubation ( 90-120 minutes ) .", "annotated_text": "Ara-C activated <protein>JNKs</protein> only after prolonged incubation ( 90-120 minutes ) ."}802{"id": "801", "text": "Thus , ceramide is not a positive signal for ERK activation in T-cell lines .", "annotated_text": "Thus , ceramide is not a positive signal for <protein>ERK</protein> activation in <cell_line>T-cell lines</cell_line> ."}803{"id": "802", "text": "The effects of Ara-C on JNK activity may be mediated through secondary response pathways .", "annotated_text": "The effects of Ara-C on <protein>JNK</protein> activity may be mediated through secondary response pathways ."}804{"id": "803", "text": "Comparative analysis identifies conserved tumor necrosis factor receptor-associated factor 3 binding sites in the human and simian Epstein-Barr virus oncogene LMP1 .", "annotated_text": "Comparative analysis identifies conserved <dna>tumor necrosis factor receptor-associated factor 3 binding sites</dna> in the <dna>human and simian Epstein-Barr virus oncogene LMP1</dna> ."}805{"id": "804", "text": "Nonhuman primates are naturally infected with a B-lymphotropic herpesvirus closely related to Epstein-Barr virus ( EBV ) .", "annotated_text": "Nonhuman primates are naturally infected with a B-lymphotropic herpesvirus closely related to Epstein-Barr virus ( EBV ) ."}806{"id": "805", "text": "These simian EBV share considerable genetic , biologic , and epidemiologic features with human EBV , including virus-induced tumorigenesis .", "annotated_text": "These simian EBV share considerable genetic , biologic , and epidemiologic features with human EBV , including virus-induced tumorigenesis ."}807{"id": "806", "text": "However , latent , transformation-associated viral genes demonstrate marked sequence divergence among species despite the conserved functions .", "annotated_text": "However , latent , transformation-associated viral genes demonstrate marked sequence divergence among species despite the conserved functions ."}808{"id": "807", "text": "We have cloned the latent membrane protein 1 ( LMP1 ) homologs from the simian EBV naturally infecting baboons ( cercopithicine herpesvirus 12 , herpesvirus papio ) and rhesus monkeys ( cercopithicine herpesvirus 15 ) for a comparative study with the human EBV oncogene .", "annotated_text": "We have cloned the <protein>latent membrane protein 1 ( LMP1 ) homologs</protein> from the simian EBV naturally infecting baboons ( cercopithicine herpesvirus 12 , herpesvirus papio ) and rhesus monkeys ( cercopithicine herpesvirus 15 ) for a comparative study with the human EBV oncogene ."}809{"id": "808", "text": "The transmembrane domains are well conserved , but there is striking sequence divergence of the carboxy-terminal cytoplasmic domain essential for B-cell immortalization and interaction with the tumor necrosis factor receptor signaling pathway .", "annotated_text": "The transmembrane domains are well conserved , but there is striking sequence divergence of the <protein>carboxy-terminal cytoplasmic domain</protein> essential for <cell_type>B-cell</cell_type> immortalization and interaction with the <protein>tumor necrosis factor receptor</protein> signaling pathway ."}810{"id": "809", "text": "Nevertheless , the simian EBV LMP1s retain most functions in common with EBV LMP1 , including the ability to induce NF- ( kappa ) B activity in human cells , to bind the tumor necrosis factor-associated factor 3 ( TRAF3 ) in vitro , and to induce expression of tumor necrosis factor-responsive genes , such as ICAM1 , in human B lymphocytes .", "annotated_text": "Nevertheless , the <protein>simian EBV LMP1s</protein> retain most functions in common with EBV <protein>LMP1</protein> , including the ability to induce <protein>NF- ( kappa ) B</protein> activity in <cell_type>human cells</cell_type> , to bind the <protein>tumor necrosis factor-associated factor 3</protein> ( <protein>TRAF3</protein> ) in vitro , and to induce expression of <dna>tumor necrosis factor-responsive genes</dna> , such as <dna>ICAM1</dna> , in <cell_type>human B lymphocytes</cell_type> ."}811{"id": "810", "text": "Multiple TRAF3 binding sites containing a PXQXT/S core sequence can be identified in the simian EBV LMP1s by an in vitro binding assay .", "annotated_text": "Multiple <dna>TRAF3 binding sites</dna> containing a <dna>PXQXT/S core sequence</dna> can be identified in the <protein>simian EBV LMP1s</protein> by an in vitro binding assay ."}812{"id": "811", "text": "A PXQXT/S-containing sequence is also present in the cytoplasmic domain of the Hodgkin 's disease marker , CD30 , and binds TRAF3 in vitro .", "annotated_text": "A <dna>PXQXT/S-containing sequence</dna> is also present in the <protein>cytoplasmic domain</protein> of the Hodgkin 's disease marker , <protein>CD30</protein> , and binds <protein>TRAF3</protein> in vitro ."}813{"id": "812", "text": "The last 13 amino acids containing a PXQXT/S sequence are highly conserved in human and simian EBV LMP1 but do not bind TRAF3 , suggesting a distinct role for this conserved region of LMP1 .", "annotated_text": "The <protein>last 13 amino acids</protein> containing a <dna>PXQXT/S sequence</dna> are highly conserved in human and simian EBV <protein>LMP1</protein> but do not bind <protein>TRAF3</protein> , suggesting a distinct role for this conserved region of <protein>LMP1</protein> ."}814{"id": "813", "text": "The conserved TRAF3 binding sites in LMP1 and the CD30 Hodgkin 's disease marker provides further evidence that a TRAF3 -mediated signal transduction pathway may be important in malignant transformation .", "annotated_text": "The conserved <dna>TRAF3 binding sites</dna> in <protein>LMP1</protein> and the <protein>CD30 Hodgkin 's disease marker</protein> provides further evidence that a <protein>TRAF3</protein> -mediated signal transduction pathway may be important in malignant transformation ."}815{"id": "814", "text": "Chromosome 1 aneusomy with 1p36 under-representation is related to histologic grade , DNA aneuploidy , high c-erb B-2 and loss of bcl-2 expression in ductal breast carcinoma .", "annotated_text": "<dna>Chromosome 1</dna> aneusomy with <dna>1p36</dna> under-representation is related to histologic grade , DNA aneuploidy , high <protein>c-erb B-2</protein> and loss of <dna>bcl-2</dna> expression in ductal breast carcinoma ."}816{"id": "815", "text": "Chromosome 1 abnormalities with loss of 1p36 have been investigated in 95 breast-cancer samples by means of a dual-target fluorescence in-situ hybridization ( FISH ) technique using the pUC 1.77 and p1-79 probes , specific for the 1q12 and 1p36 regions , respectively .", "annotated_text": "<dna>Chromosome 1</dna> abnormalities with loss of <dna>1p36</dna> have been investigated in 95 breast-cancer samples by means of a dual-target fluorescence in-situ hybridization ( FISH ) technique using the <dna>pUC 1.77</dna> and <dna>p1-79 probes</dna> , specific for the <dna>1q12 and 1p36 regions</dna> , respectively ."}817{"id": "816", "text": "Abnormalities for one or both probes were detected in 83/95 samples .", "annotated_text": "Abnormalities for one or both probes were detected in 83/95 samples ."}818{"id": "817", "text": "Relative 1p36 under-representation was found in 79/95 .", "annotated_text": "Relative <dna>1p36</dna> under-representation was found in 79/95 ."}819{"id": "818", "text": "The clinical relevance of these alterations was studied by comparing the FISH results with several parameters currently used in breast-cancer pathology .", "annotated_text": "The clinical relevance of these alterations was studied by comparing the FISH results with several parameters currently used in breast-cancer pathology ."}820{"id": "819", "text": "Distinct patterns of chromosome 1 abnormalities were found among the histologic types of breast carcinoma .", "annotated_text": "Distinct patterns of <dna>chromosome 1</dna> abnormalities were found among the histologic types of breast carcinoma ."}821{"id": "820", "text": "Lobular or mucinous samples showed few or no alterations , whereas most ductal samples had high chromosome 1 polysomy with under-representation of 1p36 .", "annotated_text": "Lobular or mucinous samples showed few or no alterations , whereas most ductal samples had high <dna>chromosome 1</dna> polysomy with under-representation of <dna>1p36</dna> ."}822{"id": "821", "text": "In ductal carcinomas , chromosome 1 alterations increased with histologic grade , DNA aneuploidy , loss of bcl-2 and high c-erb B-2 expression .", "annotated_text": "In ductal carcinomas , <dna>chromosome 1</dna> alterations increased with histologic grade , DNA aneuploidy , loss of bcl-2 and high <protein>c-erb B-2</protein> expression ."}823{"id": "822", "text": "These associations were found to be statistically significant .", "annotated_text": "These associations were found to be statistically significant ."}824{"id": "823", "text": "No correlation between chromosome 1 alterations and nuclear grade , age , size , lymph-node involvement , hormonal receptor presence , proliferation activity or p53 protein expression was detected .", "annotated_text": "No correlation between <dna>chromosome 1</dna> alterations and nuclear grade , age , size , lymph-node involvement , hormonal receptor presence , proliferation activity or <protein>p53</protein> protein expression was detected ."}825{"id": "824", "text": "These results indicate the utility of this FISH technique for a better definition of the biological characteristics of ductal carcinomas .", "annotated_text": "These results indicate the utility of this FISH technique for a better definition of the biological characteristics of ductal carcinomas ."}826{"id": "825", "text": "G ( Anh ) MTetra , a natural bacterial cell wall breakdown product , induces interleukin-1 beta and interleukin-6 expression in human monocytes .", "annotated_text": "G ( Anh ) MTetra , a natural bacterial cell wall breakdown product , induces <protein>interleukin-1 beta</protein> and <protein>interleukin-6</protein> expression in <cell_type>human monocytes</cell_type> ."}827{"id": "826", "text": "A study of the molecular mechanisms involved in inflammatory cytokine expression [ published erratum appears in J Biol Chem 1994 Jun 17 ; 269 ( 24 ) : 16983 ]", "annotated_text": "A study of the molecular mechanisms involved in <protein>inflammatory cytokine</protein> expression [ published erratum appears in J Biol Chem 1994 Jun 17 ; 269 ( 24 ) : 16983 ]"}828{"id": "827", "text": "It is believed that induction of cytokine expression by bacterial cell wall components plays a role in the development and course of sepsis .", "annotated_text": "It is believed that induction of <protein>cytokine</protein> expression by bacterial cell wall components plays a role in the development and course of sepsis ."}829{"id": "828", "text": "However , most attention has been focused on lipopolysaccharide ( LPS ) .", "annotated_text": "However , most attention has been focused on lipopolysaccharide ( LPS ) ."}830{"id": "829", "text": "We studied the ability of N-acetylglucosaminyl-1 , 6-anhydro-N-acetylmuramyl-L-alanyl-D- isoglutamyl-m-diaminopimelyl-D-alanine ( G ( Anh ) MTetra ) , a naturally occurring breakdown product of peptidoglycan that is produced by soluble lytic transglycosylase of Escherichia coli , to induce cytokine expression in human monocytes .", "annotated_text": "We studied the ability of N-acetylglucosaminyl-1 , 6-anhydro-N-acetylmuramyl-L-alanyl-D- isoglutamyl-m-diaminopimelyl-D-alanine ( G ( Anh ) MTetra ) , a naturally occurring breakdown product of peptidoglycan that is produced by soluble <protein>lytic transglycosylase</protein> of Escherichia coli , to induce <protein>cytokine</protein> expression in <cell_type>human monocytes</cell_type> ."}831{"id": "830", "text": "G ( Anh ) MTetra was found to strongly induce interleukin ( IL ) -1 beta and IL-6 mRNA expression after 2 h and IL-1 beta and IL-6 protein secretion after 48 h of activation .", "annotated_text": "G ( Anh ) MTetra was found to strongly induce <protein>interleukin ( IL ) -1 beta</protein> and <rna>IL-6 mRNA</rna> expression after 2 h and <protein>IL-1 beta</protein> and <protein>IL-6 protein</protein> secretion after 48 h of activation ."}832{"id": "831", "text": "The increase in mRNA accumulation was at least partly due to an increase in the transcription rates of the respective genes and was accompanied by a strong induction of nuclear factor-kappa B and activator protein-1 transcription factor expression .", "annotated_text": "The increase in mRNA accumulation was at least partly due to an increase in the transcription rates of the respective <dna>genes</dna> and was accompanied by a strong induction of nuclear factor-kappa B and activator protein-1 transcription factor expression ."}833{"id": "832", "text": "Experiments using inhibitors of protein kinase C , protein kinase A , and tyrosine kinase-dependent pathways revealed that G ( Anh ) MTetra-induced IL-1 beta and IL-6 mRNA expression involves activation of an H7-inhibitable pathway .", "annotated_text": "Experiments using inhibitors of <protein>protein kinase C</protein> , <protein>protein kinase A</protein> , and tyrosine kinase-dependent pathways revealed that G ( Anh ) MTetra-induced <protein>IL-1 beta</protein> and <rna>IL-6 mRNA</rna> expression involves activation of an H7-inhibitable pathway ."}834{"id": "833", "text": "By using the protein synthesis inhibitor cycloheximide , it was shown that G ( Anh ) MTetra-induced IL-6 mRNA expression depends on the synthesis of new protein , whereas G ( Anh ) MTetra-induced IL-1 beta mRNA accumulation does not .", "annotated_text": "By using the protein synthesis inhibitor cycloheximide , it was shown that G ( Anh ) MTetra-induced <rna>IL-6 mRNA</rna> expression depends on the synthesis of new protein , whereas G ( Anh ) MTetra-induced <protein>IL-1 beta</protein> mRNA accumulation does not ."}835{"id": "834", "text": "When responses to G ( Anh ) MTetra were compared with those to LPS and muramyldipeptide ( MDP ) , it was found that the optimal response to G ( Anh ) MTetra induction was similar to that of LPS but significantly higher than the response to MDP .", "annotated_text": "When responses to G ( Anh ) MTetra were compared with those to LPS and muramyldipeptide ( MDP ) , it was found that the optimal response to G ( Anh ) MTetra induction was similar to that of LPS but significantly higher than the response to MDP ."}836{"id": "835", "text": "Furthermore , maximal G ( Anh ) MTetra-induced IL-1 beta and IL-6 mRNA expression could be enhanced by co-stimulation with LPS or MDP , suggesting that different receptors and/or transduction pathways were involved .", "annotated_text": "Furthermore , maximal G ( Anh ) MTetra-induced <protein>IL-1 beta</protein> and <rna>IL-6 mRNA</rna> expression could be enhanced by co-stimulation with LPS or MDP , suggesting that different receptors and/or transduction pathways were involved ."}837{"id": "836", "text": "These results indicate that G ( Anh ) MTetra induces IL-1 beta and IL-6 expression in human monocytes suggesting a possible role for G ( Anh ) MTetra in the release of cytokines during sepsis .", "annotated_text": "These results indicate that G ( Anh ) MTetra induces <protein>IL-1 beta</protein> and <protein>IL-6</protein> expression in <cell_type>human monocytes</cell_type> suggesting a possible role for G ( Anh ) MTetra in the release of <protein>cytokines</protein> during sepsis ."}838{"id": "837", "text": "Increased proliferation , cytotoxicity , and gene expression after stimulation of human peripheral blood T lymphocytes through a surface ganglioside ( GD3 ) [ published erratum appears in J Immunol 1994 Jul 15 ; 153 ( 2 ) : 910 ]", "annotated_text": "Increased proliferation , cytotoxicity , and gene expression after stimulation of <cell_type>human peripheral blood T lymphocytes</cell_type> through a surface ganglioside ( GD3 ) [ published erratum appears in J Immunol 1994 Jul 15 ; 153 ( 2 ) : 910 ]"}839{"id": "838", "text": "Previous studies have suggested that gangliosides have an important role in cell signaling and recognition .", "annotated_text": "Previous studies have suggested that gangliosides have an important role in cell signaling and recognition ."}840{"id": "839", "text": "However , their specific function in these processes has not been clearly defined .", "annotated_text": "However , their specific function in these processes has not been clearly defined ."}841{"id": "840", "text": "A mAb , R24 , that reacts specifically with a cell surface ganglioside ( GD3 ) has been demonstrated to stimulate proliferation of T cells derived from human peripheral blood .", "annotated_text": "A <protein>mAb</protein> , <protein>R24</protein> , that reacts specifically with a cell surface ganglioside ( GD3 ) has been demonstrated to stimulate proliferation of <cell_type>T cells</cell_type> derived from human peripheral blood ."}842{"id": "841", "text": "In this study , we have investigated the mechanisms by which the R24 mAb affects T cell functions .", "annotated_text": "In this study , we have investigated the mechanisms by which the <protein>R24 mAb</protein> affects T cell functions ."}843{"id": "842", "text": "We have observed that the R24 mAb stimulates GD3+ T cell proliferation , cytotoxicity , and surface marker expression of IL-2R alpha-chain , IL-2R beta-chain , HLA-DR , CD11a , and CD11c .", "annotated_text": "We have observed that the <protein>R24 mAb</protein> stimulates GD3+ T cell proliferation , cytotoxicity , and surface marker expression of <protein>IL-2R alpha-chain</protein> , <protein>IL-2R beta-chain</protein> , <protein>HLA-DR</protein> , <protein>CD11a</protein> , and <protein>CD11c</protein> ."}844{"id": "843", "text": "Additionally , IFN-gamma activity but not IL-1 , IL-2 , or IL-4 activity was present in culture supernatants 72 h after R24 stimulation .", "annotated_text": "Additionally , <protein>IFN-gamma</protein> activity but not IL-1 , IL-2 , or IL-4 activity was present in culture supernatants 72 h after <protein>R24</protein> stimulation ."}845{"id": "844", "text": "In some donors , increased IL-6 and TNF-alpha activity also was detected after R24 treatment .", "annotated_text": "In some donors , increased <protein>IL-6</protein> and <protein>TNF-alpha</protein> activity also was detected after <protein>R24</protein> treatment ."}846{"id": "845", "text": "Furthermore , R24 treatment resulted in translocation of c-rel , but little or no NF kappa B p50 or p65 , from the cytoplasm to the nucleus and an increase of NF kappa B binding complexes containing c-rel and p50 .", "annotated_text": "Furthermore , <protein>R24</protein> treatment resulted in translocation of <protein>c-rel</protein> , but little or no <protein>NF kappa B p50</protein> or <protein>p65</protein> , from the cytoplasm to the nucleus and an increase of <protein>NF kappa B binding complexes</protein> containing <protein>c-rel</protein> and <protein>p50</protein> ."}847{"id": "846", "text": "This treatment also caused increased tyrosine phosphorylation of specific protein substrates .", "annotated_text": "This treatment also caused increased tyrosine phosphorylation of specific protein substrates ."}848{"id": "847", "text": "R24 -stimulated increases in proliferation , cytotoxicity , and cell surface protein expression could be blocked by cyclosporin and staurosporin , indicating that cyclophilin/calcineurin and protein kinase C may be involved in the R24 signaling pathway .", "annotated_text": "<protein>R24</protein> -stimulated increases in proliferation , cytotoxicity , and cell surface protein expression could be blocked by cyclosporin and staurosporin , indicating that <protein>cyclophilin/calcineurin</protein> and <protein>protein kinase C</protein> may be involved in the <protein>R24</protein> signaling pathway ."}849{"id": "848", "text": "Additionally , herbimycin A , a tyrosine kinase inhibitor , blocked the R24 -stimulated increase in proliferation but not cytotoxicity at concentrations consistent with specificity for tyrosine kinases .", "annotated_text": "Additionally , herbimycin A , a <protein>tyrosine kinase</protein> inhibitor , blocked the <protein>R24</protein> -stimulated increase in proliferation but not cytotoxicity at concentrations consistent with specificity for <protein>tyrosine kinases</protein> ."}850{"id": "849", "text": "These results suggest that multiple biochemical pathways are involved in the activation of human T cells by R24 .", "annotated_text": "These results suggest that multiple biochemical pathways are involved in the activation of <cell_type>human T cells</cell_type> by <protein>R24</protein> ."}851{"id": "850", "text": "Genes encoding general initiation factors for RNA polymerase II transcription are dispersed in the human genome .", "annotated_text": "Genes encoding <protein>general initiation factors</protein> for <protein>RNA polymerase II</protein> transcription are dispersed in the <dna>human genome</dna> ."}852{"id": "851", "text": "General transcription factors are required for accurate initiation of transcription by RNA polymerase II .", "annotated_text": "<protein>General transcription factors</protein> are required for accurate initiation of transcription by <protein>RNA polymerase II</protein> ."}853{"id": "852", "text": "Human cDNAs encoding subunits of these factors have been cloned and sequenced .", "annotated_text": "<dna>Human cDNAs</dna> encoding subunits of these factors have been cloned and sequenced ."}854{"id": "853", "text": "Using fluorescence in situ hybridization ( FISH ) , we show here that the genes encoding the TATA-box binding protein ( TBP ) , TFIIB , TFIIE alpha , TFIIE beta , RAP30 , RAP74 and the 62 kDa subunit , of TFIIH are located at the human chromosomal bands 6q26-27 , 1p21-22 , 3q21-24 , 8p12 , 13q14 , 19p13.3 and 11p14-15.1 , respectively .", "annotated_text": "Using fluorescence in situ hybridization ( FISH ) , we show here that the <dna>genes</dna> encoding the <protein>TATA-box binding protein</protein> ( <protein>TBP</protein> ) , <protein>TFIIB</protein> , <protein>TFIIE alpha</protein> , <protein>TFIIE beta</protein> , <protein>RAP30</protein> , <protein>RAP74</protein> and the <protein>62 kDa subunit</protein> , of <protein>TFIIH</protein> are located at the <dna>human chromosomal bands 6q26-27 , 1p21-22 , 3q21-24 , 8p12 , 13q14 , 19p13.3 and 11p14-15.1</dna> , respectively ."}855{"id": "854", "text": "This dispersed localization of a group of functionally related gene provides insights into the molecular mechanism of human genome evolution and their possible involvement in human diseases .", "annotated_text": "This dispersed localization of a group of functionally related gene provides insights into the molecular mechanism of <dna>human genome</dna> evolution and their possible involvement in human diseases ."}856{"id": "855", "text": "BCL-6 and the molecular pathogenesis of B-cell lymphoma .", "annotated_text": "<protein>BCL-6</protein> and the molecular pathogenesis of B-cell lymphoma ."}857{"id": "856", "text": "The results presented identify the first genetic lesion associated with DLCL , the most clinically relevant form of NHL .", "annotated_text": "The results presented identify the first genetic lesion associated with DLCL , the most clinically relevant form of NHL ."}858{"id": "857", "text": "Although no proof yet exists of a role for these lesions in DLCL pathogenesis , the feature of the BCL-6 gene product , its specific pattern of expression in B cells , and the clustering of lesions disrupting its regulatory domain strongly suggest that deregulation of BCL-6 expression may contribute to DLCL development .", "annotated_text": "Although no proof yet exists of a role for these lesions in DLCL pathogenesis , the feature of the <protein>BCL-6 gene product</protein> , its specific pattern of expression in <cell_type>B cells</cell_type> , and the clustering of lesions disrupting its regulatory domain strongly suggest that deregulation of <protein>BCL-6</protein> expression may contribute to DLCL development ."}859{"id": "858", "text": "A more precise definition of the role of BCL-6 in normal and neoplastic B-cell development is the goal of ongoing study of transgenic mice engineered either to express BCL-6 under heterologous promoters or lacking BCL-6 function due to targeted deletions .", "annotated_text": "A more precise definition of the role of <protein>BCL-6</protein> in normal and neoplastic B-cell development is the goal of ongoing study of transgenic mice engineered either to express <protein>BCL-6</protein> under <dna>heterologous promoters</dna> or lacking <protein>BCL-6</protein> function due to targeted deletions ."}860{"id": "859", "text": "In addition to contributing to the understanding of DLCL pathogenesis , the identification of BCL-6 lesions may have relevant clinical implications .", "annotated_text": "In addition to contributing to the understanding of DLCL pathogenesis , the identification of <protein>BCL-6</protein> lesions may have relevant clinical implications ."}861{"id": "860", "text": "DLCL represent a heterogeneous group of neoplasms which are treated homogeneously despite the fact that only 50 % of patients experience long-term disease-free survival ( Schneider et al. 1990 ) .", "annotated_text": "DLCL represent a heterogeneous group of neoplasms which are treated homogeneously despite the fact that only 50 % of patients experience long-term disease-free survival ( Schneider et al. 1990 ) ."}862{"id": "861", "text": "The fact that BCL-6 rearrangements identify biologically and clinically distinct subsets of DLCL suggests that these lesions may be useful as markers in selection of differential therapeutic strategies based on different risk groups .", "annotated_text": "The fact that <protein>BCL-6</protein> rearrangements identify biologically and clinically distinct subsets of DLCL suggests that these lesions may be useful as markers in selection of differential therapeutic strategies based on different risk groups ."}863{"id": "862", "text": "Furthermore , the BCL-6 rearrangements can be used to identify and monitor the malignant clone with sensitive PCR-based techniques .", "annotated_text": "Furthermore , the <protein>BCL-6</protein> rearrangements can be used to identify and monitor the <cell_type>malignant clone</cell_type> with sensitive PCR-based techniques ."}864{"id": "863", "text": "Since clinical remission has been observed in a significant fraction of DLCL cases , these markers may serve as critical tools for sensitive monitoring of minimal residual disease and early diagnosis of relapse ( Gribben et al. 1993 ) .", "annotated_text": "Since clinical remission has been observed in a significant fraction of DLCL cases , these markers may serve as critical tools for sensitive monitoring of minimal residual disease and early diagnosis of relapse ( Gribben et al. 1993 ) ."}865{"id": "864", "text": "Pancreatic development and maturation of the islet B cell .", "annotated_text": "Pancreatic development and maturation of the <cell_type>islet B cell</cell_type> ."}866{"id": "865", "text": "Studies of pluripotent islet cultures .", "annotated_text": "Studies of <cell_line>pluripotent islet cultures</cell_line> ."}867{"id": "866", "text": "Pancreas organogenesis is a highly regulated process , in which two anlage evaginate from the primitive gut .", "annotated_text": "Pancreas organogenesis is a highly regulated process , in which two anlage evaginate from the primitive gut ."}868{"id": "867", "text": "They later fuse , and , under the influence of the surrounding mesenchyme , the mature organ develops , being mainly composed of ductal , exocrine and endocrine compartments .", "annotated_text": "They later fuse , and , under the influence of the surrounding mesenchyme , the mature organ develops , being mainly composed of ductal , exocrine and endocrine compartments ."}869{"id": "868", "text": "Early buds are characterized by a branching morphogenesis of the ductal epithelium from which endocrine and exocrine precursor cells bud to eventually form the two other compartments .", "annotated_text": "Early buds are characterized by a branching morphogenesis of the ductal epithelium from which <cell_type>endocrine and exocrine precursor cells</cell_type> bud to eventually form the two other compartments ."}870{"id": "869", "text": "The three compartments are thought to be of common endodermal origin ; in contrast to earlier hypotheses , which suggested that the endocrine compartment was of neuroectodermal origin .", "annotated_text": "The three compartments are thought to be of common endodermal origin ; in contrast to earlier hypotheses , which suggested that the endocrine compartment was of neuroectodermal origin ."}871{"id": "870", "text": "It is thus generally believed that the pancreatic endocrine-lineage possesses the ability to mature along a differentiation pathway that shares many characteristics with those of neuronal differentiation .", "annotated_text": "It is thus generally believed that the pancreatic endocrine-lineage possesses the ability to mature along a differentiation pathway that shares many characteristics with those of neuronal differentiation ."}872{"id": "871", "text": "During recent years , studies of insulin-gene regulation and , in particular , the tissue-specific transcriptional control of insulin-gene activity have provided information on pancreas development in general .", "annotated_text": "During recent years , studies of <dna>insulin-gene</dna> regulation and , in particular , the tissue-specific transcriptional control of <dna>insulin-gene</dna> activity have provided information on pancreas development in general ."}873{"id": "872", "text": "The present review summarizes these findings , with a special focus on our own studies on pluripotent endocrine cultures of rat pancreas .", "annotated_text": "The present review summarizes these findings , with a special focus on our own studies on <cell_line>pluripotent endocrine cultures</cell_line> of rat pancreas ."}874{"id": "873", "text": "Octamer independent activation of transcription from the kappa immunoglobulin germline promoter .", "annotated_text": "Octamer independent activation of transcription from the <dna>kappa immunoglobulin germline promoter</dna> ."}875{"id": "874", "text": "Previous analyses of immunoglobulin V region promoters has led to the discovery of a common octamer motif which is functionally important in the tissue-specific and developmentally regulated transcriptional activation of immunoglobulin genes .", "annotated_text": "Previous analyses of <dna>immunoglobulin V region promoters</dna> has led to the discovery of a common <dna>octamer motif</dna> which is functionally important in the tissue-specific and developmentally regulated transcriptional activation of <dna>immunoglobulin genes</dna> ."}876{"id": "875", "text": "The germline promoters ( Ko ) located upstream of the J region gene segments of the kappa locus also contain an octamer motif ( containing a single base pair mutation and referred to as the variant octamer ) which has been shown previously to bind Oct-1 and Oct-2 transcription factors in vitro .", "annotated_text": "The <dna>germline promoters</dna> ( <dna>Ko</dna> ) located upstream of the <dna>J region gene segments</dna> of the <dna>kappa locus</dna> also contain an <dna>octamer motif</dna> ( containing a single <dna>base pair mutation</dna> and referred to as the variant octamer ) which has been shown previously to bind <protein>Oct-1</protein> and <protein>Oct-2</protein> <protein>transcription factors</protein> in vitro ."}877{"id": "876", "text": "To further elucidate the role of this variant octamer motif in the regulation of germline transcription from the unrearranged kappa locus , we have quantitated the relative binding affinity of Oct-1 and Oct-2 for the variant octamer motif and determined the functional role of this octamer motif in transcriptional activation .", "annotated_text": "To further elucidate the role of this variant <dna>octamer motif</dna> in the regulation of <dna>germline</dna> transcription from the unrearranged <dna>kappa locus</dna> , we have quantitated the relative binding affinity of <protein>Oct-1</protein> and <protein>Oct-2</protein> for the variant <dna>octamer motif</dna> and determined the functional role of this <dna>octamer motif</dna> in transcriptional activation ."}878{"id": "877", "text": "We find that , although the variant octamer motif binds Oct-1 and Oct-2 in vitro with 5-fold lower affinity than the consensus octamer motif , mutation of the variant octamer motif to either a consensus octamer or non-octamer motif has no effect on transcriptional activation from the germline promoter .", "annotated_text": "We find that , although the variant <dna>octamer motif</dna> binds <protein>Oct-1</protein> and <protein>Oct-2</protein> in vitro with 5-fold lower affinity than the <dna>consensus octamer motif</dna> , mutation of the variant <dna>octamer motif</dna> to either a <dna>consensus octamer</dna> or <dna>non-octamer motif</dna> has no effect on transcriptional activation from the <dna>germline promoter</dna> ."}879{"id": "878", "text": "We also find significant differences in activation of germline and V region promoters by kappa enhancers .", "annotated_text": "We also find significant differences in activation of <dna>germline</dna> and <dna>V region promoters</dna> by <dna>kappa enhancers</dna> ."}880{"id": "879", "text": "Our results suggest that the germline promoters and V region promoters differ in their dependence on octamer for activation and respond differently to enhancer activation .", "annotated_text": "Our results suggest that the <dna>germline promoters</dna> and <dna>V region promoters</dna> differ in their dependence on <dna>octamer</dna> for activation and respond differently to enhancer activation ."}881{"id": "880", "text": "These findings have important implications in regulation of germline transcription as well as concomitant activation of the V-J recombination of the kappa light chain locus .", "annotated_text": "These findings have important implications in regulation of <dna>germline</dna> transcription as well as concomitant activation of the V-J recombination of the <dna>kappa light chain locus</dna> ."}882{"id": "881", "text": "Generation of CD1+RelB+ dendritic cells and tartrate-resistant acid phosphatase-positive osteoclast-like multinucleated giant cells from human monocytes .", "annotated_text": "Generation of <cell_type>CD1+RelB+ dendritic cells</cell_type> and <cell_type>tartrate-resistant acid phosphatase-positive osteoclast-like multinucleated giant cells</cell_type> from <cell_type>human monocytes</cell_type> ."}883{"id": "882", "text": "We previously showed that granulocyte-macrophage colony-stimulating factor ( GM-CSF ) and macrophage colony-stimulating factor ( M-CSF ) stimulate the differentiation of human monocytes into two phenotypically distinct types of macrophages .", "annotated_text": "We previously showed that <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) and <protein>macrophage colony-stimulating factor</protein> ( <protein>M-CSF</protein> ) stimulate the differentiation of <cell_type>human monocytes</cell_type> into two phenotypically distinct types of <cell_type>macrophages</cell_type> ."}884{"id": "883", "text": "However , in vivo , not only CSF but also many other cytokines are produced under various conditions .", "annotated_text": "However , in vivo , not only <protein>CSF</protein> but also many other <protein>cytokines</protein> are produced under various conditions ."}885{"id": "884", "text": "Those cytokines may modulate the differentiation of monocytes by CSFs .", "annotated_text": "Those <protein>cytokines</protein> may modulate the differentiation of <cell_type>monocytes</cell_type> by <protein>CSFs</protein> ."}886{"id": "885", "text": "In the present study , we showed that CD14+ adherent human monocytes can differentiate into CD1+relB+ dendritic cells ( DC ) by the combination of GM-CSF plus interleukin-4 ( IL-4 ) and that they differentiate into tartrate-resistant acid phosphatase ( TRAP ) -positive osteoclast-like multinucleated giant cells ( MGC ) by the combination of M-CSF plus IL-4 .", "annotated_text": "In the present study , we showed that <cell_type>CD14+ adherent human monocytes</cell_type> can differentiate into <cell_type>CD1+relB+ dendritic cells</cell_type> ( <cell_type>DC</cell_type> ) by the combination of <protein>GM-CSF</protein> plus <protein>interleukin-4</protein> ( <protein>IL-4</protein> ) and that they differentiate into <cell_type>tartrate-resistant acid phosphatase ( TRAP ) -positive osteoclast-like multinucleated giant cells</cell_type> ( <cell_type>MGC</cell_type> ) by the combination of <protein>M-CSF</protein> plus <protein>IL-4</protein> ."}887{"id": "886", "text": "However , the monocyte-derived DC were not terminally differentiated cells ; they could still convert to macrophages in response to M-CSF .", "annotated_text": "However , the <cell_line>monocyte-derived DC</cell_line> were not <cell_line>terminally differentiated cells</cell_line> ; they could still convert to <cell_type>macrophages</cell_type> in response to <protein>M-CSF</protein> ."}888{"id": "887", "text": "Tumor necrosis factor-alpha ( TNF-alpha ) stimulated the terminal differentiation of the DC by downregulating the expression of the M-CSF receptor , cfms mRNA , and aborting the potential to convert to macrophages .", "annotated_text": "<protein>Tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) stimulated the terminal differentiation of the <cell_type>DC</cell_type> by downregulating the expression of the <protein>M-CSF receptor</protein> , <rna>cfms mRNA</rna> , and aborting the potential to convert to <cell_type>macrophages</cell_type> ."}889{"id": "888", "text": "In contrast to IL-4 , interferon-gamma ( IFN-gamma ) had no demonstrable effect on the differentiation of monocytes .", "annotated_text": "In contrast to <protein>IL-4</protein> , <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) had no demonstrable effect on the differentiation of <cell_type>monocytes</cell_type> ."}890{"id": "889", "text": "Rather , IFN-gamma antagonized the effect of IL-4 and suppressed the DC and MGC formation induced by GM-CSF + IL-4 and M-CSF + IL-4 , respectively .", "annotated_text": "Rather , <protein>IFN-gamma</protein> antagonized the effect of <protein>IL-4</protein> and suppressed the <cell_type>DC</cell_type> and <cell_type>MGC</cell_type> formation induced by <protein>GM-CSF</protein> + <protein>IL-4</protein> and <protein>M-CSF</protein> + <protein>IL-4</protein> , respectively ."}891{"id": "890", "text": "Taken together , these results provide a new aspect to our knowledge of monocyte differentiation and provide evidence that human monocytes are flexible in their differentiation potential and are precursors not only of macrophages but also of CD1+relB+DC and TRAP-positive MGC .", "annotated_text": "Taken together , these results provide a new aspect to our knowledge of monocyte differentiation and provide evidence that <cell_type>human monocytes</cell_type> are flexible in their differentiation potential and are precursors not only of <cell_type>macrophages</cell_type> but also of <cell_type>CD1+relB+DC</cell_type> and <cell_type>TRAP-positive MGC</cell_type> ."}892{"id": "891", "text": "Such a diverse pathway of monocyte differentiation may constitute one of the basic mechanisms of immune regulation .", "annotated_text": "Such a diverse pathway of monocyte differentiation may constitute one of the basic mechanisms of immune regulation ."}893{"id": "892", "text": "The NF-kappa B inhibitor , tepoxalin , suppresses surface expression of the cell adhesion molecules CD62E , CD11b/CD18 and CD106 .", "annotated_text": "The <protein>NF-kappa B</protein> inhibitor , tepoxalin , suppresses surface expression of the <protein>cell adhesion molecules</protein> <protein>CD62E</protein> , <protein>CD11b/CD18</protein> and <protein>CD106</protein> ."}894{"id": "893", "text": "Tepoxalin , a dual enzyme inhibitor of cyclooxygenase and 5-lipoxygenase has been shown to inhibit T-cell activation .", "annotated_text": "Tepoxalin , a dual enzyme inhibitor of <protein>cyclooxygenase</protein> and <protein>5-lipoxygenase</protein> has been shown to inhibit T-cell activation ."}895{"id": "894", "text": "Its immunosuppressive property is distinct from cyclosporin because only tepoxalin , but not cyclosporin , suppresses NF-kappa B activation .", "annotated_text": "Its immunosuppressive property is distinct from cyclosporin because only tepoxalin , but not cyclosporin , suppresses <protein>NF-kappa B</protein> activation ."}896{"id": "895", "text": "Here we report that tepoxalin selectively inhibits intercellular adhesion molecule-1 ( ICAM-1 , CD54 ) /MAC-1 ( CD11b/CD18 ) dependent adhesion of polymorphonuclear cells to IL-1 activated human umbilical vein endothelial cells .", "annotated_text": "Here we report that tepoxalin selectively inhibits <protein>intercellular adhesion molecule-1</protein> <protein>( ICAM-1 , CD54 ) /MAC-1</protein> ( <protein>CD11b/CD18</protein> ) dependent adhesion of <cell_type>polymorphonuclear cells</cell_type> to <protein>IL-1</protein> activated <cell_type>human umbilical vein endothelial cells</cell_type> ."}897{"id": "896", "text": "The mechanism of inhibition is related to the surface expression of several cell adhesion molecules .", "annotated_text": "The mechanism of inhibition is related to the surface expression of several cell <protein>adhesion molecules</protein> ."}898{"id": "897", "text": "Flow cytometry analyses on cultured cells that were treated with tepoxalin or antisense oligonucleotides to the P65/p50 subunit of NF-kappa B , and then stimulated with PMA , revealed a reduced expression of CD11b/CD18 on monocytic HL60 cells , and endothelial adhesion molecule-1 ( CD62E ) and vascular adhesion molecule-1 ( CD106 ) on human umbilical vein endothelial cells .", "annotated_text": "Flow cytometry analyses on cultured cells that were treated with tepoxalin or antisense oligonucleotides to the <protein>P65/p50 subunit</protein> of <protein>NF-kappa B</protein> , and then stimulated with PMA , revealed a reduced expression of <protein>CD11b/CD18</protein> on <cell_line>monocytic HL60 cells</cell_line> , and <protein>endothelial adhesion molecule-1</protein> ( <protein>CD62E</protein> ) and <protein>vascular adhesion molecule-1</protein> ( <protein>CD106</protein> ) on <cell_type>human umbilical vein endothelial cells</cell_type> ."}899{"id": "898", "text": "Expression of other adhesion molecules such as lymphocyte function associated-antigen-1 ( CD11a/CD18 ) and CD54 were unaffected .", "annotated_text": "Expression of other <protein>adhesion molecules</protein> such as <protein>lymphocyte function associated-antigen-1</protein> ( <protein>CD11a/CD18</protein> ) and <protein>CD54</protein> were unaffected ."}900{"id": "899", "text": "Tepoxalin also inhibited the secretion of a NF-kappa B regulated chemokine , IL-8 , a known inducer of CD11b/CD18 expression .", "annotated_text": "Tepoxalin also inhibited the secretion of a <protein>NF-kappa B regulated chemokine</protein> , <protein>IL-8</protein> , a known inducer of <protein>CD11b/CD18</protein> expression ."}901{"id": "900", "text": "Thus the suppression of CD11b/CD18 expression by tepoxalin may involve IL-8 .", "annotated_text": "Thus the suppression of <protein>CD11b/CD18</protein> expression by tepoxalin may involve <protein>IL-8</protein> ."}902{"id": "901", "text": "Our results suggest that by inhibiting NF-kappa B activation , surface expression of several adhesion molecules can be modulated and that tepoxalin may be useful in treating selected adhesion mediated events such as leukocyte migration or atherosclerotic plaque formation .", "annotated_text": "Our results suggest that by inhibiting <protein>NF-kappa B</protein> activation , surface expression of several <protein>adhesion molecules</protein> can be modulated and that tepoxalin may be useful in treating selected adhesion mediated events such as leukocyte migration or atherosclerotic plaque formation ."}903{"id": "902", "text": "Characterization of a CD43/leukosialin -mediated pathway for inducing apoptosis in human T-lymphoblastoid cells .", "annotated_text": "Characterization of a <protein>CD43/leukosialin</protein> -mediated pathway for inducing apoptosis in <cell_type>human T-lymphoblastoid cells</cell_type> ."}904{"id": "903", "text": "The monoclonal antibody ( mAb ) J393 induces apoptosis in Jurkat T-cells .", "annotated_text": "The <protein>monoclonal antibody</protein> ( <protein>mAb</protein> ) <protein>J393</protein> induces apoptosis in <cell_line>Jurkat T-cells</cell_line> ."}905{"id": "904", "text": "NH2 -terminal amino acid sequence analysis identified the 140-kDa surface antigen for mAb J393 as CD43/leukosialin , the major sialoglycoprotein of leukocytes .", "annotated_text": "<protein>NH2</protein> -terminal amino acid sequence analysis identified the <protein>140-kDa surface antigen</protein> for <protein>mAb J393</protein> as <protein>CD43/leukosialin</protein> , the major <protein>sialoglycoprotein</protein> of <cell_type>leukocytes</cell_type> ."}906{"id": "905", "text": "While Jurkat cells co-expressed two discrete cell-surface isoforms of CD43 , recognized by mAb J393 and mAb G10-2 , respectively , only J393/CD43 signaled apoptosis .", "annotated_text": "While <cell_line>Jurkat cells</cell_line> co-expressed two discrete <protein>cell-surface isoforms</protein> of <protein>CD43</protein> , recognized by <protein>mAb J393</protein> and <protein>mAb G10-2</protein> , respectively , only <protein>J393/CD43</protein> signaled apoptosis ."}907{"id": "906", "text": "J393/CD43 was found to be hyposialylated , bearing predominantly O-linked monosaccharide glycans , whereas G10-2/CD43 bore complex sialylated tetra- and hexasaccharide chains .", "annotated_text": "<protein>J393/CD43</protein> was found to be hyposialylated , bearing predominantly O-linked monosaccharide glycans , whereas <protein>G10-2/CD43</protein> bore complex sialylated tetra- and hexasaccharide chains ."}908{"id": "907", "text": "Treatment with soluble , bivalent mAb J393 killed 25-50 % of the cell population , while concomitant engagement of either the CD3.TcR complex or the integrins CD18 and CD29 significantly potentiated this effect .", "annotated_text": "Treatment with soluble , bivalent <protein>mAb J393</protein> killed 25-50 % of the <cell_line>cell population</cell_line> , while concomitant engagement of either the <protein>CD3.TcR complex</protein> or the <protein>integrins</protein> <protein>CD18</protein> and <protein>CD29</protein> significantly potentiated this effect ."}909{"id": "908", "text": "Treatment of Jurkat cells with mAb J393 induced tyrosine phosphorylation of specific protein substrates that underwent hyperphosphorylation upon antigen receptor costimulation .", "annotated_text": "Treatment of <cell_line>Jurkat cells</cell_line> with <protein>mAb J393</protein> induced tyrosine phosphorylation of specific <protein>protein substrates</protein> that underwent hyperphosphorylation upon <protein>antigen receptor</protein> costimulation ."}910{"id": "909", "text": "Tyrosine kinase inhibition by herbimycin A diminished J393/CD43 -mediated apoptosis , whereas inhibition of phosphotyrosine phosphatase activity by bis ( maltolato ) oxovanadium-IV enhanced cell death .", "annotated_text": "<protein>Tyrosine kinase</protein> inhibition by herbimycin A diminished <protein>J393/CD43</protein> -mediated apoptosis , whereas inhibition of <protein>phosphotyrosine phosphatase</protein> activity by bis ( maltolato ) oxovanadium-IV enhanced cell death ."}911{"id": "910", "text": "Signal transduction through tyrosine kinase activation may lead to altered gene expression , as J393/ CD43 ligation prompted decreases in the nuclear localization of the transcriptional regulatory protein NF-kappaB and proteins binding the interferon-inducible regulatory element .", "annotated_text": "Signal transduction through tyrosine kinase activation may lead to altered gene expression , as J393/ <protein>CD43</protein> ligation prompted decreases in the nuclear localization of the <protein>transcriptional regulatory protein</protein> <protein>NF-kappaB</protein> and proteins binding the <dna>interferon-inducible regulatory element</dna> ."}912{"id": "911", "text": "Since peripheral blood T-lymphocytes express cryptic epitopes for mAb J393 , these findings demonstrate the existence of a tightly regulated CD43 -mediated pathway for inducing apoptosis in human T-cell lineages .", "annotated_text": "Since <cell_type>peripheral blood T-lymphocytes</cell_type> express <protein>cryptic epitopes</protein> for <protein>mAb J393</protein> , these findings demonstrate the existence of a tightly regulated <protein>CD43</protein> -mediated pathway for inducing apoptosis in <cell_type>human T-cell lineages</cell_type> ."}913{"id": "912", "text": "Sterol dependent LDL-receptor gene transcription in lymphocytes from normal and CML patients .", "annotated_text": "Sterol dependent <dna>LDL-receptor gene</dna> transcription in <cell_type>lymphocytes</cell_type> from normal and CML patients ."}914{"id": "913", "text": "Sterol regulatory element ( SRE ) has been recognized to regulate various key genes coding for especially low density lipoprotein ( LDL ) -receptor , 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase and HMG-CoA synthase known to play a crucial role in the cholesterol feedback mechanism .", "annotated_text": "<dna>Sterol regulatory element</dna> ( <dna>SRE</dna> ) has been recognized to regulate various key <dna>genes</dna> coding for especially <protein>low density lipoprotein ( LDL ) -receptor</protein> , <protein>3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase</protein> and <protein>HMG-CoA synthase</protein> known to play a crucial role in the cholesterol feedback mechanism ."}915{"id": "914", "text": "The deranged cholesterol feedback mechanism has been widely recognised in initiation as well as progression of various types of cancers including chronic myeloid leukaemia ( CML ) .", "annotated_text": "The deranged cholesterol feedback mechanism has been widely recognised in initiation as well as progression of various types of cancers including chronic myeloid leukaemia ( CML ) ."}916{"id": "915", "text": "Consequently , the present study was addressed to understand this phenomenon and revealed the existence of a unique 47 kDa protein factor having affinity for this SRE sequence in lymphocytes from normal subjects as well as its absence in lymphocytes from untreated CML patients .", "annotated_text": "Consequently , the present study was addressed to understand this phenomenon and revealed the existence of a <protein>unique 47 kDa protein factor</protein> having affinity for this <dna>SRE sequence</dna> in <cell_type>lymphocytes</cell_type> from normal subjects as well as its absence in <cell_type>lymphocytes</cell_type> from untreated CML patients ."}917{"id": "916", "text": "However , this factor appeared when the CML patients achieved complete haematological remission ( CHR ) through alpha-interferon therapy .", "annotated_text": "However , this factor appeared when the CML patients achieved complete haematological remission ( CHR ) through <protein>alpha-interferon</protein> therapy ."}918{"id": "917", "text": "Further , an inverse relationship was also observed between sterol modulated LDL-receptor gene transcription and the binding affinity of this 47 kDa factor to the SRE sequence .", "annotated_text": "Further , an inverse relationship was also observed between sterol modulated <dna>LDL-receptor gene</dna> transcription and the binding affinity of this <protein>47 kDa factor</protein> to the <dna>SRE sequence</dna> ."}919{"id": "918", "text": "Based upon these results we propose that alpha-interferon through its receptor initiates phosphatidic acid dependent signalling which in turn regulates the affinity of 47 kDa sterol regulatory element binding factor as well as LDL-receptor gene transcription in lymphocytes from CML patients .", "annotated_text": "Based upon these results we propose that <protein>alpha-interferon</protein> through its receptor initiates phosphatidic acid dependent signalling which in turn regulates the affinity of <protein>47 kDa sterol regulatory element binding factor</protein> as well as <dna>LDL-receptor gene</dna> transcription in <cell_type>lymphocytes</cell_type> from CML patients ."}920{"id": "919", "text": "Multiple prolactin-responsive elements mediate G1 and S phase expression of the interferon regulatory factor-1 gene .", "annotated_text": "Multiple <dna>prolactin-responsive elements</dna> mediate G1 and S phase expression of the <dna>interferon regulatory factor-1 gene</dna> ."}921{"id": "920", "text": "The interferon regulatory factor-1 ( IRF-1 ) gene is both an immediate-early G1 phase gene and an S phase gene inducible by PRL in rat Nb2 T lymphocytes .", "annotated_text": "The <dna>interferon regulatory factor-1 ( IRF-1 ) gene</dna> is both an <dna>immediate-early G1 phase gene</dna> and an <dna>S phase gene</dna> inducible by <protein>PRL</protein> in <cell_line>rat Nb2 T lymphocytes</cell_line> ."}922{"id": "921", "text": "To understand the mechanism by which PRL regulates the biphasic expression of IRF-1 , we cloned the rat IRF-1 gene and functionally characterized the IRF-1 promoter .", "annotated_text": "To understand the mechanism by which <protein>PRL</protein> regulates the biphasic expression of <protein>IRF-1</protein> , we cloned the <dna>rat IRF-1 gene</dna> and functionally characterized the <dna>IRF-1 promoter</dna> ."}923{"id": "922", "text": "Upon transfection into Nb2 T cells , 1.7 kilobases ( kb ) of IRF-1 5'-flanking DNA linked to a chloramphenicol acetyl transferase ( CAT ) reporter gene mediated a 30-fold induction of CAT enzyme activity in response to 24 h of PRL stimulation .", "annotated_text": "Upon transfection into <cell_line>Nb2 T cells</cell_line> , 1.7 kilobases ( kb ) of <dna>IRF-1 5'-flanking DNA</dna> linked to a <dna>chloramphenicol acetyl transferase ( CAT ) reporter gene</dna> mediated a 30-fold induction of <protein>CAT enzyme</protein> activity in response to 24 h of <protein>PRL</protein> stimulation ."}924{"id": "923", "text": "Deletion mutants containing 1.3 , 0.6 , and 0.2 kb 5'-flanking DNA were incrementally less transcriptionally active , although 0.2 kb still mediated a 12-fold induction by PRL .", "annotated_text": "Deletion mutants containing <dna>1.3 , 0.6 , and 0.2 kb 5'-flanking DNA</dna> were incrementally less transcriptionally active , although 0.2 kb still mediated a 12-fold induction by <protein>PRL</protein> ."}925{"id": "924", "text": "The sequence between -1.7 and -0.2 kb linked to a heterologous thymidine kinase promoter failed to respond to PRL stimulation , suggesting that the activity of upstream PRL response elements may require an interaction with promoter-proximal elements .", "annotated_text": "The sequence between -1.7 and -0.2 kb linked to a <dna>heterologous thymidine kinase promoter</dna> failed to respond to <protein>PRL</protein> stimulation , suggesting that the activity of <dna>upstream PRL response elements</dna> may require an interaction with <dna>promoter-proximal elements</dna> ."}926{"id": "925", "text": "By assaying CAT enzyme activity across a 24-h PRL induction time course , we were able to assign G1 vs. S phase PRL responses of the IRF-1 gene to different regions of the IRF-1 5'-flanking and promoter DNA .", "annotated_text": "By assaying <protein>CAT enzyme</protein> activity across a 24-h <protein>PRL</protein> induction time course , we were able to assign G1 vs. S phase <protein>PRL</protein> responses of the <dna>IRF-1 gene</dna> to different regions of the <protein>IRF-1</protein> <dna>5'-flanking</dna> and <dna>promoter DNA</dna> ."}927{"id": "926", "text": "The 0.2-kb IRF-CAT construct was induced by PRL stimulation during the G1 phase of the cell cycle .", "annotated_text": "The 0.2-kb <dna>IRF-CAT construct</dna> was induced by <protein>PRL</protein> stimulation during the G1 phase of the cell cycle ."}928{"id": "927", "text": "In contrast , the 1.7-kb IRF- CAT construct was inducible by PRL during both G1 and S phase of the cell cycle .", "annotated_text": "In contrast , the 1.7-kb IRF- <protein>CAT</protein> construct was inducible by <protein>PRL</protein> during both G1 and S phase of the cell cycle ."}929{"id": "928", "text": "Hence , the PRL -induced biphasic expression of the IRF-1 gene appears to be controlled by separate PRL-responsive elements : elements in the first 0.2 kb of the IRF-1 promoter region act during early activation , and elements between 0.2 and 1.7 kb act in concert with the proximal 0.2-kb region during S phase progression .", "annotated_text": "Hence , the <protein>PRL</protein> -induced biphasic expression of the <dna>IRF-1 gene</dna> appears to be controlled by separate <dna>PRL-responsive elements</dna> : elements in the first 0.2 kb of the <dna>IRF-1 promoter region</dna> act during early activation , and elements between 0.2 and 1.7 kb act in concert with the proximal 0.2-kb region during S phase progression ."}930{"id": "929", "text": "Regulation of the BZLF1 promoter of Epstein-Barr virus by second messengers in anti-immunoglobulin-treated B cells .", "annotated_text": "Regulation of the <dna>BZLF1 promoter</dna> of Epstein-Barr virus by second messengers in <cell_line>anti-immunoglobulin-treated B cells</cell_line> ."}931{"id": "930", "text": "Initiation of the Epstein-Barr virus ( EBV ) lytic cycle is dependent on the transcription of the BZLF1 gene .", "annotated_text": "Initiation of the Epstein-Barr virus ( EBV ) lytic cycle is dependent on the transcription of the <dna>BZLF1 gene</dna> ."}932{"id": "931", "text": "The BZLF1 gene promoter ( Zp ) was activated by crosslinking of cell surface immunoglobulin ( Ig ) with anti-Ig antibody in B cells , even in the absence of other viral genes .", "annotated_text": "The <dna>BZLF1 gene promoter</dna> ( <dna>Zp</dna> ) was activated by crosslinking of <protein>cell surface immunoglobulin</protein> ( <protein>Ig</protein> ) with <protein>anti-Ig antibody</protein> in <cell_type>B cells</cell_type> , even in the absence of other viral genes ."}933{"id": "932", "text": "We identified several anti-Ig response elements within Zp , which were originally defined as 12-O-tetradecanoylphorbol-13-acetate ( TPA ) response elements ( ZI repeats and ZII , an AP-1-like domain ) .", "annotated_text": "We identified several anti-Ig response elements within <dna>Zp</dna> , which were originally defined as <dna>12-O-tetradecanoylphorbol-13-acetate ( TPA ) response elements</dna> ( ZI repeats and <dna>ZII</dna> , an <dna>AP-1-like domain</dna> ) ."}934{"id": "933", "text": "Since anti-Ig crosslinking leads to activation of protein kinase C ( PKC ) and an increase in intracellular calcium level , Zp was tested for the response to these cellular factors .", "annotated_text": "Since anti-Ig crosslinking leads to activation of <protein>protein kinase C</protein> ( <protein>PKC</protein> ) and an increase in intracellular calcium level , <dna>Zp</dna> was tested for the response to these <protein>cellular factors</protein> ."}935{"id": "934", "text": "Treatment with calcium ionophore A23187 increased Zp activity .", "annotated_text": "Treatment with calcium ionophore A23187 increased <dna>Zp</dna> activity ."}936{"id": "935", "text": "When the calcium ionophore was used in conjunction with TPA , a PKC activator , the Zp induction was synergistically enhanced .", "annotated_text": "When the calcium ionophore was used in conjunction with TPA , a <protein>PKC</protein> activator , the <dna>Zp</dna> induction was synergistically enhanced ."}937{"id": "936", "text": "1- ( 5-Isoquinolinyl sulfonyl ) -2-methylpiperazine , an inhibitor of PKC , inhibited the anti-Ig inducibility of Zp .", "annotated_text": "1- ( 5-Isoquinolinyl sulfonyl ) -2-methylpiperazine , an inhibitor of <protein>PKC</protein> , inhibited the <protein>anti-Ig</protein> inducibility of <dna>Zp</dna> ."}938{"id": "937", "text": "Calmodulin antagonists , compound R24571 and trifluoperazine , blocked the Zp activation with anti-Ig .", "annotated_text": "Calmodulin antagonists , compound R24571 and trifluoperazine , blocked the <dna>Zp</dna> activation with <protein>anti-Ig</protein> ."}939{"id": "938", "text": "These findings suggest that Zp responds directly to changes in the activity of both PKC and calcium/calmodulin-dependent protein kinase .", "annotated_text": "These findings suggest that <dna>Zp</dna> responds directly to changes in the activity of both <protein>PKC</protein> and <protein>calcium/calmodulin-dependent protein kinase</protein> ."}940{"id": "939", "text": "Requirement of tyrosine kinase activation for the anti-Ig -mediated Zp activation was also demonstrated through the use of the tyrosine kinase inhibitor herbimycin .", "annotated_text": "Requirement of <protein>tyrosine kinase</protein> activation for the <protein>anti-Ig</protein> -mediated <dna>Zp</dna> activation was also demonstrated through the use of the tyrosine kinase inhibitor herbimycin ."}941{"id": "940", "text": "These cellular gene regulatory molecules induced with anti-Ig may cooperatively play an important part in achieving efficient EBV activation as seen with anti-Ig treatment in B cells .", "annotated_text": "These <protein>cellular gene regulatory molecules</protein> induced with anti-Ig may cooperatively play an important part in achieving efficient EBV activation as seen with <protein>anti-Ig</protein> treatment in <cell_type>B cells</cell_type> ."}942{"id": "941", "text": "The SCL protein displays cell-specific heterogeneity in size .", "annotated_text": "The <protein>SCL protein</protein> displays cell-specific heterogeneity in size ."}943{"id": "942", "text": "SCL protein production was examined in a variety of hemopoietic cell lines by immunoblotting using specific polyclonal antisera .", "annotated_text": "<protein>SCL protein</protein> production was examined in a variety of <cell_line>hemopoietic cell lines</cell_line> by immunoblotting using specific polyclonal antisera ."}944{"id": "943", "text": "SCL protein was detected in erythroid , megakaryocyte , mast and early myeloid cell lines , as well as in several lymphoid leukemia cell lines which are known to harbor SCL gene rearrangements .", "annotated_text": "<protein>SCL protein</protein> was detected in <cell_line>erythroid , megakaryocyte , mast and early myeloid cell lines</cell_line> , as well as in several <cell_line>lymphoid leukemia cell lines</cell_line> which are known to harbor <dna>SCL gene rearrangements</dna> ."}945{"id": "944", "text": "In most cell lines , proteins of molecular weight 49 and 44 kDa were found , however two myeloid cell lines expressed only lower molecular weight species of 24 and 22 kDa .", "annotated_text": "In most cell lines , proteins of molecular weight 49 and 44 kDa were found , however two myeloid cell lines expressed only lower <protein>molecular weight species of 24 and 22 kDa</protein> ."}946{"id": "945", "text": "This size discrepancy appeared to be due to cell-specific translational regulation , since overexpression of a retrovirally transfected SCL gene yielded the higher molecular weight forms in most cell lines ( GP+E-86 , AT2.5 , M1 ) but only the 22 kDa form in the myeloid cell line , WEHI-3B/D+ .", "annotated_text": "This size discrepancy appeared to be due to cell-specific translational regulation , since overexpression of a retrovirally transfected <dna>SCL gene</dna> yielded the higher molecular weight forms in most <cell_line>cell lines</cell_line> ( <cell_line>GP+E-86</cell_line> , <cell_line>AT2.5</cell_line> , <cell_line>M1</cell_line> ) but only the <protein>22 kDa form</protein> in the <cell_line>myeloid cell line</cell_line> , <cell_line>WEHI-3B/D+</cell_line> ."}947{"id": "946", "text": "Overexpression of full-length SCL protein in the lymphoid cell lines , SupT1 and Raji , did not alter cell phenotype and there was no evidence for autoregulation of SCL transcription .", "annotated_text": "Overexpression of full-length <protein>SCL protein</protein> in the <cell_line>lymphoid cell lines</cell_line> , SupT1 and Raji , did not alter cell phenotype and there was no evidence for autoregulation of <protein>SCL</protein> transcription ."}948{"id": "947", "text": "The restricted pattern of SCL protein synthesis is consistent with the restricted expression of SCL mRNA documented previously .", "annotated_text": "The restricted pattern of <protein>SCL protein</protein> synthesis is consistent with the restricted expression of <rna>SCL mRNA</rna> documented previously ."}949{"id": "948", "text": "In addition , the present results indicate that SCL protein size was determined by regulation of translation in a cell-specific manner .", "annotated_text": "In addition , the present results indicate that <protein>SCL protein</protein> size was determined by regulation of translation in a cell-specific manner ."}950{"id": "949", "text": "Description and functional implications of a novel mutation in the sex-determining gene SRY .", "annotated_text": "Description and functional implications of a novel mutation in the <dna>sex-determining gene</dna> <dna>SRY</dna> ."}951{"id": "950", "text": "The sex-determining gene SRY was screened for molecular alteration in an XY sex-reversed female by single-strand conformation polymorphism ( SSCP ) technique .", "annotated_text": "The sex-determining gene <dna>SRY</dna> was screened for molecular alteration in an XY sex-reversed female by single-strand conformation polymorphism ( SSCP ) technique ."}952{"id": "951", "text": "An A-to-G transition was detected which leads to an exchange of a tyrosine by a cysteine in the SRY protein .", "annotated_text": "An A-to-G transition was detected which leads to an exchange of a tyrosine by a cysteine in the <protein>SRY protein</protein> ."}953{"id": "952", "text": "The affected tyrosine residue located at the C terminus of the DNA binding protein is evolutionarily strongly conserved among the members of the HMG box containing proteins .", "annotated_text": "The affected tyrosine residue located at the <protein>C terminus</protein> of the <protein>DNA binding protein</protein> is evolutionarily strongly conserved among the members of the <protein>HMG box containing proteins</protein> ."}954{"id": "953", "text": "Using gel shift assay and peptide synthesis such a mutation is shown to abolish the SRY protein DNA binding ability .", "annotated_text": "Using gel shift assay and peptide synthesis such a mutation is shown to abolish the <dna>SRY</dna> protein DNA binding ability ."}955{"id": "954", "text": "The involvement of this particular amino acid in the binding specificity is also discussed .", "annotated_text": "The involvement of this particular amino acid in the binding specificity is also discussed ."}956{"id": "955", "text": "Induction of tyrosine phosphorylation and T-cell activation by vanadate peroxide , an inhibitor of protein tyrosine phosphatases .", "annotated_text": "Induction of tyrosine phosphorylation and <cell_type>T-cell</cell_type> activation by vanadate peroxide , an inhibitor of <protein>protein tyrosine phosphatases</protein> ."}957{"id": "956", "text": "Rapid tyrosine phosphorylation of key cellular proteins is a crucial event in the transduction of activation signals to T-lymphocytes .", "annotated_text": "Rapid tyrosine phosphorylation of key cellular proteins is a crucial event in the transduction of activation signals to <cell_type>T-lymphocytes</cell_type> ."}958{"id": "957", "text": "The regulatory role of protein tyrosine phosphatases ( PTPases ) in this process was explored by studying the effects of a powerful PTPase inhibitor , vanadate peroxide ( pervanadate ) , on the activation cascade of Jurkat human leukaemic T-cells .", "annotated_text": "The regulatory role of <protein>protein tyrosine phosphatases</protein> ( <protein>PTPases</protein> ) in this process was explored by studying the effects of a powerful <protein>PTPase</protein> inhibitor , vanadate peroxide ( pervanadate ) , on the activation cascade of <cell_line>Jurkat human leukaemic T-cells</cell_line> ."}959{"id": "958", "text": "Pervanadate induced activation of the tyrosine kinases lck and fyn ( 4- and 3-fold respectively ) and a dramatic increase in tyrosine phosphorylation of cellular proteins , notably phospholipase C gamma 1 .", "annotated_text": "Pervanadate induced activation of the <protein>tyrosine kinases</protein> <protein>lck</protein> and <protein>fyn</protein> ( 4- and 3-fold respectively ) and a dramatic increase in tyrosine phosphorylation of <protein>cellular proteins</protein> , notably <protein>phospholipase C gamma 1</protein> ."}960{"id": "959", "text": "After this event , we observed a rise in intracellular Ca2+ concentration , corresponding to an influx .", "annotated_text": "After this event , we observed a rise in intracellular Ca2+ concentration , corresponding to an influx ."}961{"id": "960", "text": "This effect required surface expression of the CD45 PTPase and was not observed in CD45-deficient variants of Jurkat cells .", "annotated_text": "This effect required surface expression of the <protein>CD45 PTPase</protein> and was not observed in <cell_line>CD45-deficient variants</cell_line> of <cell_line>Jurkat cells</cell_line> ."}962{"id": "961", "text": "In the CD45-negative variant , the effect of pervanadate on tyrosine phosphorylation was globally decreased and some phosphorylated substrates were specifically missing .", "annotated_text": "In the <cell_line>CD45-negative variant</cell_line> , the effect of pervanadate on tyrosine phosphorylation was globally decreased and some phosphorylated substrates were specifically missing ."}963{"id": "962", "text": "Pervanadate also stimulated transcription of the c-fos gene and accumulation of its mRNA as well as several other hallmarks of T-lymphocyte activation such as surface expression of the CD69 antigen and the interleukin 2 receptor alpha-chain ( CD25 ) .", "annotated_text": "Pervanadate also stimulated transcription of the <dna>c-fos gene</dna> and accumulation of its <rna>mRNA</rna> as well as several other hallmarks of <cell_type>T-lymphocyte</cell_type> activation such as surface expression of the CD69 antigen and the interleukin 2 receptor alpha-chain ( CD25 ) ."}964{"id": "963", "text": "Pervanadate synergized with signals delivered by T-cell antigen receptor engagement or by a phorbol ester to induce interleukin 2 production .", "annotated_text": "Pervanadate synergized with signals delivered by <cell_type>T-cell</cell_type> <protein>antigen receptor</protein> engagement or by a phorbol ester to induce interleukin 2 production ."}965{"id": "964", "text": "Pervanadate activated NF-kappa B , as shown by an increase in DNA-binding activity of this transcription factor .", "annotated_text": "<protein>Pervanadate activated NF-kappa B</protein> , as shown by an increase in DNA-binding activity of this <protein>transcription factor</protein> ."}966{"id": "965", "text": "We thus conclude that PTPases play a crucial role in the negative regulation of signal transduction culminating in T-lymphocyte activation .", "annotated_text": "We thus conclude that <protein>PTPases</protein> play a crucial role in the negative regulation of signal transduction culminating in <cell_type>T-lymphocyte</cell_type> activation ."}967{"id": "966", "text": "Moreover , induction of tyrosine phosphorylation appears sufficient per se to initiate a complete activation programme .", "annotated_text": "Moreover , induction of tyrosine phosphorylation appears sufficient per se to initiate a complete activation programme ."}968{"id": "967", "text": "Activation of nuclear factor-kappaB via T cell receptor requires a Raf kinase and Ca2+ influx .", "annotated_text": "Activation of <protein>nuclear factor-kappaB</protein> via <protein>T cell receptor</protein> requires a <protein>Raf kinase</protein> and Ca2+ influx ."}969{"id": "968", "text": "Functional synergy between Raf and calcineurin .", "annotated_text": "Functional synergy between <protein>Raf</protein> and <protein>calcineurin</protein> ."}970{"id": "969", "text": "Signals transduced via the TCR activate the transcription factor nuclear factor-kappaB ( NF-kappaB ) , which , in turn , is critical to the transcriptional induction of many genes important for the proliferation and expression of a differentiated phenotype .", "annotated_text": "Signals transduced via the <protein>TCR</protein> activate the <protein>transcription factor</protein> <protein>nuclear factor-kappaB</protein> ( <protein>NF-kappaB</protein> ) , which , in turn , is critical to the transcriptional induction of many genes important for the proliferation and expression of a differentiated phenotype ."}971{"id": "970", "text": "Treatment of T cells with the protein kinase C activator PMA in combination with Ca2+ ionophores mimics this process , and the two agents are often substituted for TCR stimulation , bypassing the TCR .", "annotated_text": "Treatment of <cell_type>T cells</cell_type> with the <protein>protein kinase C</protein> activator PMA in combination with Ca2+ ionophores mimics this process , and the two agents are often substituted for <protein>TCR</protein> stimulation , bypassing the <protein>TCR</protein> ."}972{"id": "971", "text": "Here we identify intracellular signaling components involved in activation of NF-kappaB following TCR stimulation .", "annotated_text": "Here we identify intracellular signaling components involved in activation of <protein>NF-kappaB</protein> following <protein>TCR</protein> stimulation ."}973{"id": "972", "text": "TCR signaling was triggered by treating Jurkat T cells with PHA or anti-CD3 Abs , and NF-kappaB activation was monitored by electrophoretic mobility shift assays and/or by kappaB -dependent reporter assays .", "annotated_text": "<protein>TCR</protein> signaling was triggered by treating <cell_line>Jurkat T cells</cell_line> with <protein>PHA</protein> or <protein>anti-CD3 Abs</protein> , and <protein>NF-kappaB</protein> activation was monitored by electrophoretic mobility shift assays and/or by <protein>kappaB</protein> -dependent reporter assays ."}974{"id": "973", "text": "Contrary to the idea that protein kinase C is involved in TCR -mediated activation of NF-kappaB , high doses of staurosporine did not interfere with activation of NF-kappaB by PHA , while the same dose of staurosporine completely blocked activation by PMA .", "annotated_text": "Contrary to the idea that <protein>protein kinase C</protein> is involved in <protein>TCR</protein> -mediated activation of <protein>NF-kappaB</protein> , high doses of staurosporine did not interfere with activation of <protein>NF-kappaB</protein> by <protein>PHA</protein> , while the same dose of staurosporine completely blocked activation by PMA ."}975{"id": "974", "text": "PHA -induced kappaB-dependent reporter activity was , however , effectively blocked by a dominant negative form of Raf-1 , suggesting a critical role for a Raf kinase .", "annotated_text": "<protein>PHA</protein> -induced kappaB-dependent reporter activity was , however , effectively blocked by a dominant negative form of <protein>Raf-1</protein> , suggesting a critical role for a <protein>Raf kinase</protein> ."}976{"id": "975", "text": "The TCR -mediated activation of NF-kappaB was also dependent on a Ca2+ influx , because the Ca2+ channel blocker , SK & F 96365 , as well as other agents that prevented the Ca2+ influx , inhibited NF-kappaB activation .", "annotated_text": "The <protein>TCR</protein> -mediated activation of <protein>NF-kappaB</protein> was also dependent on a Ca2+ influx , because the Ca2+ channel blocker , SK & F 96365 , as well as other agents that prevented the Ca2+ influx , inhibited <protein>NF-kappaB</protein> activation ."}977{"id": "976", "text": "Cotransfection of a constitutively active form of calcineurin largely substituted for the Ca2+ requirement and reversed the blockade by SK & F 96365 .", "annotated_text": "Cotransfection of a constitutively active form of <protein>calcineurin</protein> largely substituted for the Ca2+ requirement and reversed the blockade by SK & F 96365 ."}978{"id": "977", "text": "Consistent with these observations , coexpression of constitutively active forms of Raf-1 and calcineurin synergistically induced kappaB -dependent reporter activity , suggesting a physiologically relevant functional interaction between the kinase and the phosphatase .", "annotated_text": "Consistent with these observations , coexpression of constitutively active forms of <protein>Raf-1</protein> and <protein>calcineurin</protein> synergistically induced <protein>kappaB</protein> -dependent reporter activity , suggesting a physiologically relevant functional interaction between the <protein>kinase</protein> and the <protein>phosphatase</protein> ."}979{"id": "978", "text": "Synergistic interactions between overlapping binding sites for the serum response factor and ELK-1 proteins mediate both basal enhancement and phorbol ester responsiveness of primate cytomegalovirus major immediate-early promoters in monocyte and T-lymphocyte cell types .", "annotated_text": "Synergistic interactions between <dna>overlapping binding sites</dna> for the <protein>serum response factor</protein> and <protein>ELK-1 proteins</protein> mediate both basal enhancement and phorbol ester responsiveness of <dna>primate cytomegalovirus major immediate-early promoters</dna> in monocyte and <cell_type>T-lymphocyte</cell_type> cell types ."}980{"id": "979", "text": "Cytomegalovirus ( CMV ) infection is nonpermissive or persistent in many lymphoid and myeloid cell types but can be activated in differentiated macrophages .", "annotated_text": "Cytomegalovirus ( CMV ) infection is nonpermissive or persistent in many <cell_type>lymphoid and myeloid cell types</cell_type> but can be activated in <cell_type>differentiated macrophages</cell_type> ."}981{"id": "980", "text": "We have shown elsewhere that both the major immediate-early gene ( MIE ) and lytic cycle infectious progeny virus expression can be induced in otherwise nonpermissive monocyte-like U-937 cell cultures infected with either human CMV ( HCMV ) or simian CMV ( SCMV ) by treatment with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate ( TPA ) .", "annotated_text": "We have shown elsewhere that both the <dna>major immediate-early gene</dna> ( <dna>MIE</dna> ) and lytic cycle infectious progeny virus expression can be induced in otherwise nonpermissive <cell_line>monocyte-like U-937 cell cultures</cell_line> infected with either human CMV ( HCMV ) or simian CMV ( SCMV ) by treatment with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate ( TPA ) ."}982{"id": "981", "text": "Two multicopy basal enhancer motifs within the SCMV MIE enhancer , namely , 11 copies of the 16-bp cyclic AMP response element ( CRE ) and 3 copies of novel 17-bp serum response factor ( SRF ) binding sites referred to as the SNE ( SRF/NFkappaB-like element ) , as well as four classical NFkappaB sites within the HCMV version , contribute to TPA responsiveness in transient assays in monocyte and T-cell types .", "annotated_text": "Two <dna>multicopy basal enhancer motifs</dna> within the SCMV <dna>MIE enhancer</dna> , namely , 11 copies of the 16-bp <dna>cyclic AMP response element</dna> ( <dna>CRE</dna> ) and 3 copies of novel 17-bp <dna>serum response factor ( SRF ) binding sites</dna> referred to as the <dna>SNE</dna> ( <dna>SRF/NFkappaB-like element</dna> ) , as well as four classical <dna>NFkappaB sites</dna> within the HCMV version , contribute to TPA responsiveness in transient assays in <cell_type>monocyte and T-cell types</cell_type> ."}983{"id": "982", "text": "The SCMV SNE sites contain potential overlapping core recognition binding motifs for SRF , Rel/NFkappaB , ETS , and YY1 class transcription factors but fail to respond to either serum or tumor necrosis factor alpha .", "annotated_text": "The <dna>SCMV SNE sites</dna> contain potential overlapping core recognition binding motifs for <protein>SRF</protein> , <protein>Rel/NFkappaB</protein> , <protein>ETS</protein> , and <protein>YY1 class transcription factors</protein> but fail to respond to either <protein>serum or tumor necrosis factor alpha</protein> ."}984{"id": "983", "text": "Therefore , to evaluate the mechanism of TPA responsiveness of the SNE motifs and of a related 16-bp SEE ( SRF/ETS element ) motif found in the HCMV and chimpanzee CMV MIE enhancers , we have examined the functional responses and protein binding properties of multimerized wild-type and mutant elements added upstream to the SCMV MIE or simian virus 40 minimal promoter regions in the U-937 , K-562 , HL-60 , THP-1 , and Jurkat cell lines .", "annotated_text": "Therefore , to evaluate the mechanism of TPA responsiveness of the <dna>SNE motifs</dna> and of a related 16-bp <dna>SEE</dna> ( <dna>SRF/ETS element</dna> ) motif found in the <dna>HCMV and chimpanzee CMV MIE enhancers</dna> , we have examined the functional responses and protein binding properties of <dna>multimerized wild-type and mutant elements</dna> added upstream to the <dna>SCMV MIE</dna> or <dna>simian virus 40 minimal promoter regions</dna> in the <cell_line>U-937</cell_line> , <cell_line>K-562</cell_line> , <cell_line>HL-60</cell_line> , <cell_line>THP-1</cell_line> , and <cell_line>Jurkat cell lines</cell_line> ."}985{"id": "984", "text": "Unlike classical NFkappaB sites , neither the SNE nor the SEE motif responded to phosphatase inhibition by okadaic acid .", "annotated_text": "Unlike classical <dna>NFkappaB sites</dna> , neither the <dna>SNE</dna> nor the <dna>SEE motif</dna> responded to phosphatase inhibition by okadaic acid ."}986{"id": "985", "text": "However , the TPA responsiveness of both CMV elements proved to involve synergistic interactions between the core SRF binding site ( CCATATATGG ) and the adjacent inverted ETS binding motifs ( TTCC ) , which correlated directly with formation of a bound tripartite complex containing both the cellular SRF and ELK-1 proteins .", "annotated_text": "However , the TPA responsiveness of both <dna>CMV elements</dna> proved to involve synergistic interactions between the core <dna>SRF binding site</dna> ( CCATATATGG ) and the adjacent inverted <dna>ETS binding motifs</dna> ( TTCC ) , which correlated directly with formation of a bound <protein>tripartite complex</protein> containing both the cellular <protein>SRF</protein> and <protein>ELK-1 proteins</protein> ."}987{"id": "986", "text": "This protein complex was more abundant in U-937 , K-562 , and HeLa cell extracts than in Raji , HF , BALB/c 3T3 , or HL-60 cells , but the binding activity was altered only twofold after TPA treatment .", "annotated_text": "This <protein>protein complex</protein> was more abundant in U-937 , K-562 , and HeLa cell extracts than in <cell_line>Raji</cell_line> , <cell_line>HF</cell_line> , <cell_line>BALB/c 3T3</cell_line> , or <cell_line>HL-60 cells</cell_line> , but the binding activity was altered only twofold after TPA treatment ."}988{"id": "987", "text": "A 40-fold stimulation of chloramphenicol acetyltransferase activity mediated by four tandem repeats of the SNE could be induced within 2 h ( and up to 250-fold within 6 h ) after addition of TPA in DNA-transfected U-937 cells , indicating that the stimulation appeared likely to be a true protein kinase C -mediated signal transduction event rather than a differentiation response .", "annotated_text": "A 40-fold stimulation of <protein>chloramphenicol acetyltransferase</protein> activity mediated by four <dna>tandem repeats</dna> of the <dna>SNE</dna> could be induced within 2 h ( and up to 250-fold within 6 h ) after addition of TPA in <cell_line>DNA-transfected U-937 cells</cell_line> , indicating that the stimulation appeared likely to be a true <protein>protein kinase C</protein> -mediated signal transduction event rather than a differentiation response ."}989{"id": "988", "text": "Slight differences in the sequence of the core SRF binding site compared with that of the classical c-Fos promoter serum response element , together with differences in the spacing between the SRF and ETS motifs , appear to account for the inability of the SCMV SNEs to respond to serum induction .", "annotated_text": "Slight differences in the sequence of the <dna>core SRF binding site</dna> compared with that of the classical <dna>c-Fos promoter serum response element</dna> , together with differences in the spacing between the <dna>SRF and ETS motifs</dna> , appear to account for the inability of the <dna>SCMV SNEs</dna> to respond to serum induction ."}990{"id": "989", "text": "T-cell -directed TAL-1 expression induces T-cell malignancies in transgenic mice .", "annotated_text": "<cell_type>T-cell</cell_type> -directed <protein>TAL-1</protein> expression induces T-cell malignancies in transgenic mice ."}991{"id": "990", "text": "The TAL-1 gene specifies for a basic domain-helix-loop-helix protein , which is involved in the control of normal hematopoiesis .", "annotated_text": "The <dna>TAL-1 gene</dna> specifies for a basic <protein>domain-helix-loop-helix protein</protein> , which is involved in the control of normal hematopoiesis ."}992{"id": "991", "text": "In human pathology , the TAL-1 gene product is expressed in a high percentage of T-cell acute lymphoblastic leukemias in the pediatric age range ; however , it has not been established whether the expression has a causal role in oncogenesis .", "annotated_text": "In human pathology , the <protein>TAL-1 gene product</protein> is expressed in a high percentage of <cell_type>T-cell</cell_type> acute lymphoblastic leukemias in the pediatric age range ; however , it has not been established whether the expression has a causal role in oncogenesis ."}993{"id": "992", "text": "In this report , we describe the phenotype of mouse transgenic lines obtained by inducing tal-1 protein expression in lymphoid tissues using the LCK promoter .", "annotated_text": "In this report , we describe the phenotype of <cell_line>mouse transgenic lines</cell_line> obtained by inducing <protein>tal-1 protein</protein> expression in lymphoid tissues using the <dna>LCK promoter</dna> ."}994{"id": "993", "text": "The survival rate of tal-1 transgenic animals was much lower as compared with control mice .", "annotated_text": "The survival rate of <dna>tal-1</dna> transgenic animals was much lower as compared with control mice ."}995{"id": "994", "text": "Histopathological analysis revealed lymphomas of T-cell type , often comprising a minor B-cell component .", "annotated_text": "Histopathological analysis revealed lymphomas of T-cell type , often comprising a minor B-cell component ."}996{"id": "995", "text": "Some mice showed marked splenic lymphocyte depletion .", "annotated_text": "Some mice showed marked splenic lymphocyte depletion ."}997{"id": "996", "text": "Primary lymphocyte cultures showed partial independence from exogenous growth stimuli and increased resistance to low-serum apoptosis .", "annotated_text": "<cell_line>Primary lymphocyte cultures</cell_line> showed partial independence from exogenous growth stimuli and increased resistance to low-serum apoptosis ."}998{"id": "997", "text": "To further unravel the tal-1 oncogenic potential , a strain of tal-1 transgenic mice was crossbred with p53-/- mice ; the survival rate in these animals was reduced by more than one-half when compared with that of tal-1 mice , and histopathological analysis revealed exclusively T-cell lymphomas .", "annotated_text": "To further unravel the <dna>tal-1</dna> oncogenic potential , a strain of <dna>tal-1</dna> transgenic mice was crossbred with p53-/- mice ; the survival rate in these animals was reduced by more than one-half when compared with that of <dna>tal-1</dna> mice , and histopathological analysis revealed exclusively <cell_type>T-cell</cell_type> lymphomas ."}999{"id": "998", "text": "These data indicate that TAL-1 , expressed in T cells , is per se a potent oncogene , which may exert a key leukemogenetic role in the majority of T-cell acute lymphoblastic leukemias .", "annotated_text": "These data indicate that <protein>TAL-1</protein> , expressed in <cell_type>T cells</cell_type> , is per se a potent oncogene , which may exert a key leukemogenetic role in the majority of <cell_type>T-cell</cell_type> acute lymphoblastic leukemias ."}1000{"id": "999", "text": "Tissue and cell-type specific expression of the tuberous sclerosis gene , TSC2 , in human tissues .", "annotated_text": "Tissue and cell-type specific expression of the <dna>tuberous sclerosis gene</dna> , <dna>TSC2</dna> , in human tissues ."}1001{"id": "1000", "text": "TSC2 is a gene on chromosome 16p13.3 associated with the autosomal dominant neurocutaneous disorder , tuberous sclerosis complex ( TSC ) .", "annotated_text": "<dna>TSC2</dna> is a gene on <dna>chromosome 16p13.3</dna> associated with the autosomal dominant neurocutaneous disorder , tuberous sclerosis complex ( TSC ) ."}1002{"id": "1001", "text": "By using a partial nucleotide sequence from the cloned TSC2 and polymerase chain reaction methodology , we constructed a digoxigenin-labeled complementary DNA probe to examine TSC2 gene expression in autopsy- or biopsy-derived human tissues by in situ hybridization .", "annotated_text": "By using a partial nucleotide sequence from the cloned <dna>TSC2</dna> and polymerase chain reaction methodology , we constructed a <dna>digoxigenin-labeled complementary DNA probe</dna> to examine <dna>TSC2</dna> gene expression in autopsy- or biopsy-derived human tissues by in situ hybridization ."}1003{"id": "1002", "text": "TSC2 messenger RNA was widely expressed in various cell types throughout the body , including epithelia , lymphocytes , and cells with endocrine functions , e.g. , adrenal cortex and anterior pituitary .", "annotated_text": "<rna>TSC2 messenger RNA</rna> was widely expressed in various cell types throughout the body , including epithelia , <cell_type>lymphocytes</cell_type> , and cells with endocrine functions , e.g. , adrenal cortex and anterior pituitary ."}1004{"id": "1003", "text": "It was prominently and selectively ( within the central nervous system ) expressed in pyramidal cells of the cerebral cortex and other motor neurons , e.g. , in spinal cord and brainstem nuclei .", "annotated_text": "It was prominently and selectively ( within the central nervous system ) expressed in <cell_type>pyramidal cells</cell_type> of the cerebral cortex and other <cell_type>motor neurons</cell_type> , e.g. , in spinal cord and brainstem nuclei ."}1005{"id": "1004", "text": "Visceral TSC2 expression was comparable in autopsy tissues from patients with and without TSC ; TSC2 messenger RNA expression was most prominent in cells with a rapid mitotic rate and turnover , e.g. , epithelia and lymphocytes , with central nervous system pyramidal cells and other neurons being an obvious exception , and/or in cells with important secretory/transport functions .", "annotated_text": "Visceral <dna>TSC2</dna> expression was comparable in autopsy tissues from patients with and without TSC ; <dna>TSC2</dna> messenger RNA expression was most prominent in cells with a rapid mitotic rate and turnover , e.g. , epithelia and <cell_type>lymphocytes</cell_type> , with central nervous system <cell_type>pyramidal cells</cell_type> and other neurons being an obvious exception , and/or in cells with important secretory/transport functions ."}1006{"id": "1005", "text": "This widespread expression of the TSC2 gene supports the view that it encodes a protein vital to cell growth and metabolism or one that functions as a tumor/growth suppressor .", "annotated_text": "This widespread expression of the <dna>TSC2 gene</dna> supports the view that it encodes a protein vital to cell growth and metabolism or one that functions as a tumor/growth suppressor ."}1007{"id": "1006", "text": "Apoptosis signaling pathways in normal T cells : differential activity of Bcl-2 and IL-1beta-converting enzyme family protease inhibitors on glucocorticoid- and Fas-mediated cytotoxicity .", "annotated_text": "Apoptosis signaling pathways in normal <cell_type>T cells</cell_type> : differential activity of <protein>Bcl-2</protein> and <protein>IL-1beta-converting enzyme family</protein> protease inhibitors on glucocorticoid- and Fas-mediated cytotoxicity ."}1008{"id": "1007", "text": "Fas -mediated apoptosis plays an important role in regulating the immune response in peripheral T cells .", "annotated_text": "<protein>Fas</protein> -mediated apoptosis plays an important role in regulating the immune response in <cell_type>peripheral T cells</cell_type> ."}1009{"id": "1008", "text": "Restimulation of T cell blasts up-regulates Fas and Fas ligand expression , with subsequent interaction leading to cell death .", "annotated_text": "Restimulation of <cell_type>T cell blasts</cell_type> up-regulates <protein>Fas</protein> and <protein>Fas</protein> ligand expression , with subsequent interaction leading to cell death ."}1010{"id": "1009", "text": "Overexpression of Bcl-2 in tumor cells blocks apoptosis induced by many stimuli , but inhibition of Fas -mediated killing has not been consistently observed .", "annotated_text": "Overexpression of <protein>Bcl-2</protein> in <cell_type>tumor cells</cell_type> blocks apoptosis induced by many stimuli , but inhibition of <protein>Fas</protein> -mediated killing has not been consistently observed ."}1011{"id": "1010", "text": "To examine the behavior of Bcl-2 in normal cells , T cell blasts were transiently transfected with Bcl-2 and related gene products to determine the effect on apoptotic signaling .", "annotated_text": "To examine the behavior of <protein>Bcl-2</protein> in <cell_type>normal cells</cell_type> , <cell_type>T cell blasts</cell_type> were transiently transfected with <protein>Bcl-2</protein> and related <protein>gene products</protein> to determine the effect on apoptotic signaling ."}1012{"id": "1011", "text": "Transient overexpression of Bcl-2 in mouse and human T cell blasts did not block Fas -mediated apoptosis , whereas etoposide- and glucocorticoid-induced cytotoxicity was potently inhibited .", "annotated_text": "Transient overexpression of <protein>Bcl-2</protein> in mouse and human <cell_type>T cell blasts</cell_type> did not block <protein>Fas</protein> -mediated apoptosis , whereas etoposide- and glucocorticoid-induced cytotoxicity was potently inhibited ."}1013{"id": "1012", "text": "Expression of Bcl-xL and adenovirus E1B 19K did not interfere with anti- Fas killing .", "annotated_text": "Expression of <protein>Bcl-xL</protein> and <protein>adenovirus E1B 19K</protein> did not interfere with anti- <protein>Fas</protein> killing ."}1014{"id": "1013", "text": "In contrast , interleukin-1beta-converting enzyme family protease inhibitors Ac-DEVD-CHO and CrmA blocked Fas -mediated apoptosis .", "annotated_text": "In contrast , interleukin-1beta-converting enzyme family protease inhibitors Ac-DEVD-CHO and CrmA blocked <protein>Fas</protein> -mediated apoptosis ."}1015{"id": "1014", "text": "These results suggest that peripheral T cells use distinct apoptosis signaling pathways with differential sensitivity to Bcl-2 and interleukin-1beta-converting enzyme family protease inhibitors .", "annotated_text": "These results suggest that <cell_type>peripheral T cells</cell_type> use distinct apoptosis signaling pathways with differential sensitivity to <protein>Bcl-2</protein> and interleukin-1beta-converting enzyme family protease inhibitors ."}1016{"id": "1015", "text": "Since T cells normally express Bcl-2 and Bcl-xL following activation , their inability to block Fas -mediated apoptosis may allow for the elimination of self-reactive cells and the appropriate regulation of immune responses .", "annotated_text": "Since <cell_type>T cells</cell_type> normally express <protein>Bcl-2</protein> and <protein>Bcl-xL</protein> following activation , their inability to block <protein>Fas</protein> -mediated apoptosis may allow for the elimination of <cell_type>self-reactive cells</cell_type> and the appropriate regulation of immune responses ."}1017{"id": "1016", "text": "Increased interleukin 2 transcription in murine lymphocytes by ciprofloxacin .", "annotated_text": "Increased <protein>interleukin 2</protein> transcription in <cell_type>murine lymphocytes</cell_type> by ciprofloxacin ."}1018{"id": "1017", "text": "The fluoroquinolone antibiotic , ciprofloxacin ( cipro ) , induces hyperproduction of interleukin 2 ( IL-2 ) and interferon-gamma ( IFN-gamma ) in stimulated human peripheral blood lymphocytes .", "annotated_text": "The fluoroquinolone antibiotic , ciprofloxacin ( cipro ) , induces hyperproduction of <protein>interleukin 2</protein> ( <protein>IL-2</protein> ) and <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) in stimulated <cell_type>human peripheral blood lymphocytes</cell_type> ."}1019{"id": "1018", "text": "In this investigation an enhanced and prolonged IL-2 and IL-2 mRNA response was also detected in both stimulated ( T cell mitogens or alloantigens ) murine splenocytes and in the stimulated murine T cell line EL-4 in the presence of ciprofloxacin ( 5-80 micrograms/ml ) as compared to control cells without antibiotics .", "annotated_text": "In this investigation an enhanced and prolonged <protein>IL-2</protein> and <rna>IL-2 mRNA</rna> response was also detected in both stimulated ( <protein>T cell mitogens</protein> or <protein>alloantigens</protein> ) <cell_type>murine splenocytes</cell_type> and in the stimulated <cell_line>murine T cell line EL-4</cell_line> in the presence of ciprofloxacin ( 5-80 micrograms/ml ) as compared to control cells without antibiotics ."}1020{"id": "1019", "text": "However , in contrast to human lymphocytes , IFN-gamma production was inhibited and IFN-gamma mRNA levels were unaffected at 24 h and only slightly upregulated at 48 and 72 h of culture in murine splenocytes incubated with cipro ( 20 micrograms/ml ) .", "annotated_text": "However , in contrast to <cell_type>human lymphocytes</cell_type> , <protein>IFN-gamma</protein> production was inhibited and <rna>IFN-gamma mRNA</rna> levels were unaffected at 24 h and only slightly upregulated at 48 and 72 h of culture in <cell_type>murine splenocytes</cell_type> incubated with cipro ( 20 micrograms/ml ) ."}1021{"id": "1020", "text": "EL-4 cells were transfected with a plasmid containing the IL-2 promoter and enhancer region linked to the chloramphenicol acetyltransferase ( CAT ) reporter gene .", "annotated_text": "<cell_type>EL-4 cells</cell_type> were transfected with a plasmid containing the <dna>IL-2 promoter</dna> and <dna>enhancer region</dna> linked to the <dna>chloramphenicol acetyltransferase ( CAT ) reporter gene</dna> ."}1022{"id": "1021", "text": "Analysis of CAT activity revealed that cipro enhanced IL-2 gene induction .", "annotated_text": "Analysis of <protein>CAT</protein> activity revealed that cipro enhanced IL-2 gene induction ."}1023{"id": "1022", "text": "In addition , EL-4 cells incubated with ciprofloxacin showed an early peak and more activated nuclear factor of activated T cells ( NFAT-1 ) as compared to control cells without antibiotics .", "annotated_text": "In addition , <cell_type>EL-4 cells</cell_type> incubated with ciprofloxacin showed an early peak and more activated nuclear factor of <cell_type>activated T cells</cell_type> ( <protein>NFAT-1</protein> ) as compared to control cells without antibiotics ."}1024{"id": "1023", "text": "Cipro did not affect the nuclear transcription factors AP-1 or NFIL-2A .", "annotated_text": "Cipro did not affect the <protein>nuclear transcription factors</protein> <protein>AP-1</protein> or <protein>NFIL-2A</protein> ."}1025{"id": "1024", "text": "Taken together , cipro inhibited IFN-gamma synthesis , but enhanced IL-2 production in murine lymphocytes by means of influencing NFAT-1 and causing an increased IL-2 transcription .", "annotated_text": "Taken together , cipro inhibited <protein>IFN-gamma</protein> synthesis , but enhanced <protein>IL-2</protein> production in <cell_type>murine lymphocytes</cell_type> by means of influencing <protein>NFAT-1</protein> and causing an increased <protein>IL-2</protein> transcription ."}1026{"id": "1025", "text": "Human T-cell leukemia virus type I Tax associates with and is negatively regulated by the NF-kappa B2 p100 gene product : implications for viral latency .", "annotated_text": "Human T-cell leukemia virus type I <protein>Tax</protein> associates with and is negatively regulated by the <protein>NF-kappa B2 p100 gene product</protein> : implications for viral latency ."}1027{"id": "1026", "text": "Human T-cell leukemia virus type I ( HTLV-I ) is the etiologic agent of the adult T-cell leukemia , an aggressive and often fatal malignancy of activated human CD4 T cells .", "annotated_text": "Human T-cell leukemia virus type I ( HTLV-I ) is the etiologic agent of the adult T-cell leukemia , an aggressive and often fatal malignancy of <cell_line>activated human CD4 T cells</cell_line> ."}1028{"id": "1027", "text": "HTLV-I encodes an essential 40-kDa protein termed Tax that not only transactivates the long terminal repeat of this retrovirus but also induces an array of cellular genes .", "annotated_text": "HTLV-I encodes an essential <protein>40-kDa protein</protein> termed <protein>Tax</protein> that not only transactivates the long terminal repeat of this retrovirus but also induces an array of <dna>cellular genes</dna> ."}1029{"id": "1028", "text": "Tax -mediated transformation of T cells likely involves the deregulated expression of various cellular genes that normally regulate lymphocyte growth produced by altered activity of various endogenous host transcription factors .", "annotated_text": "<protein>Tax</protein> -mediated transformation of <cell_type>T cells</cell_type> likely involves the deregulated expression of various <dna>cellular genes</dna> that normally regulate <cell_type>lymphocyte</cell_type> growth produced by altered activity of various endogenous host <protein>transcription factors</protein> ."}1030{"id": "1029", "text": "In particular , Tax is capable of modulating the expression or activity of various host transcription factors , including members of the NF-kappa B/Rel and CREB/ATF families , as well as the cellular factors HEB-1 and p67SRF .", "annotated_text": "In particular , <protein>Tax</protein> is capable of modulating the expression or activity of various host <protein>transcription factors</protein> , including members of the <protein>NF-kappa B/Rel</protein> and <protein>CREB/ATF families</protein> , as well as the <protein>cellular factors</protein> <protein>HEB-1</protein> and <protein>p67SRF</protein> ."}1031{"id": "1030", "text": "An additional distinguishing characteristic of HTLV-I infection is the profound state of viral latency that is present in circulating primary leukemic T cells .", "annotated_text": "An additional distinguishing characteristic of HTLV-I infection is the profound state of viral latency that is present in circulating <cell_type>primary leukemic T cells</cell_type> ."}1032{"id": "1031", "text": "In this study , we demonstrate that HTLV-I Tax can physically associate with p100 , the product of the Rel-related NF-kappa B2 gene , both in transfected cells and in HTLV-I-infected leukemic T-cell lines .", "annotated_text": "In this study , we demonstrate that HTLV-I <protein>Tax</protein> can physically associate with <protein>p100</protein> , the product of the <dna>Rel-related NF-kappa B2 gene</dna> , both in <cell_line>transfected cells</cell_line> and in <cell_line>HTLV-I-infected leukemic T-cell lines</cell_line> ."}1033{"id": "1032", "text": "Furthermore , the physical interaction of Tax with p100 leads to the inhibition of Tax -induced activation of the HTLV-I and human immunodeficiency virus type 1 long terminal repeats , reflecting p100 -mediated cytoplasmic sequestration of the normally nuclearly expressed Tax protein .", "annotated_text": "Furthermore , the physical interaction of <protein>Tax</protein> with <protein>p100</protein> leads to the inhibition of <protein>Tax</protein> -induced activation of the HTLV-I and <dna>human immunodeficiency virus type 1 long terminal repeats</dna> , reflecting <protein>p100</protein> -mediated cytoplasmic sequestration of the normally nuclearly expressed <protein>Tax protein</protein> ."}1034{"id": "1033", "text": "In contrast , a mutant of Tax that selectively fails to activate nuclear NF-kappa B expression does not associate with p100 .", "annotated_text": "In contrast , a mutant of <protein>Tax</protein> that selectively fails to activate nuclear <protein>NF-kappa B</protein> expression does not associate with <protein>p100</protein> ."}1035{"id": "1034", "text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"}1036{"id": "1035", "text": "Rhabdomyosarcomas do not contain mutations in the DNA binding domains of myogenic transcription factors .", "annotated_text": "Rhabdomyosarcomas do not contain mutations in the DNA binding domains of myogenic <protein>transcription factors</protein> ."}1037{"id": "1036", "text": "Skeletal myogenesis is regulated by a group of transcription factors ( MyoD , myogenin , myf5 , and myf6 ) that are `` basic helix-loop-helix '' proteins that bind to the promoters of muscle-specific genes and promote their expression .", "annotated_text": "Skeletal myogenesis is regulated by a group of <protein>transcription factors</protein> ( <protein>MyoD</protein> , <protein>myogenin</protein> , <protein>myf5</protein> , and <protein>myf6</protein> ) that are <protein>`` basic helix-loop-helix '' proteins</protein> that bind to the <dna>promoters</dna> of <dna>muscle-specific genes</dna> and promote their expression ."}1038{"id": "1037", "text": "We have previously shown that after a mutation of Leu122 to Arg the DNA binding basic domain of MyoD confers c-myc -like functional characteristics to the protein .", "annotated_text": "We have previously shown that after a mutation of Leu122 to Arg the <protein>DNA binding basic domain</protein> of <protein>MyoD</protein> confers <dna>c-myc</dna> -like functional characteristics to the protein ."}1039{"id": "1038", "text": "In this study we used single-strand conformation polymorphism analysis to determine whether such mutations occur naturally in rhabdomyosarcomas .", "annotated_text": "In this study we used single-strand conformation polymorphism analysis to determine whether such mutations occur naturally in rhabdomyosarcomas ."}1040{"id": "1039", "text": "We have found that the basic domains of all the myogenic factors remain unaltered in rhabdomyosarcomas .", "annotated_text": "We have found that the <protein>basic domains</protein> of all the <protein>myogenic factors</protein> remain unaltered in rhabdomyosarcomas ."}1041{"id": "1040", "text": "Selection against such mutations may be the result of functional redundancy of these myogenic transcription factors .", "annotated_text": "Selection against such mutations may be the result of functional redundancy of these <protein>myogenic transcription factors</protein> ."}1042{"id": "1041", "text": "Function and activation of NF-kappa B in the immune system .", "annotated_text": "Function and activation of <protein>NF-kappa B</protein> in the immune system ."}1043{"id": "1042", "text": "NF-kappa B is a ubiquitous transcription factor .", "annotated_text": "<protein>NF-kappa B</protein> is a <protein>ubiquitous transcription factor</protein> ."}1044{"id": "1043", "text": "Nevertheless , its properties seem to be most extensively exploited in cells of the immune system .", "annotated_text": "Nevertheless , its properties seem to be most extensively exploited in cells of the immune system ."}1045{"id": "1044", "text": "Among these properties are NF-kappa B 's rapid posttranslational activation in response to many pathogenic signals , its direct participation in cytoplasmic/nuclear signaling , and its potency to activate transcription of a great variety of genes encoding immunologically relevant proteins .", "annotated_text": "Among these properties are <protein>NF-kappa B</protein> 's rapid posttranslational activation in response to many pathogenic signals , its direct participation in cytoplasmic/nuclear signaling , and its potency to activate transcription of a great variety of genes encoding <protein>immunologically relevant proteins</protein> ."}1046{"id": "1045", "text": "In vertebrates , five distinct DNA binding subunits are currently known which might extensively heterodimerize , thereby forming complexes with distinct transcriptional activity , DNA sequence specificity , and cell type- and cell stage-specific distribution .", "annotated_text": "In vertebrates , five distinct <protein>DNA binding subunits</protein> are currently known which might extensively heterodimerize , thereby forming complexes with distinct transcriptional activity , DNA sequence specificity , and cell type- and cell stage-specific distribution ."}1047{"id": "1046", "text": "The activity of DNA binding NF-kappa B dimers is tightly controlled by accessory proteins called I kappa B subunits of which there are also five different species currently known in vertebrates .", "annotated_text": "The activity of <protein>DNA binding NF-kappa B dimers</protein> is tightly controlled by <protein>accessory proteins</protein> called <protein>I kappa B subunits</protein> of which there are also five different species currently known in vertebrates ."}1048{"id": "1047", "text": "I kappa B proteins inhibit DNA binding and prevent nuclear uptake of NF-kappa B complexes .", "annotated_text": "<protein>I kappa B proteins</protein> inhibit DNA binding and prevent nuclear uptake of <protein>NF-kappa B complexes</protein> ."}1049{"id": "1048", "text": "An exception is the Bcl-3 protein which in addition can function as a transcription activating subunit in th nucleus .", "annotated_text": "An exception is the <protein>Bcl-3 protein</protein> which in addition can function as a <protein>transcription activating subunit</protein> in th nucleus ."}1050{"id": "1049", "text": "Other I kappa B proteins are rather involved in terminating NF-kappa B 's activity in the nucleus .", "annotated_text": "Other <protein>I kappa B proteins</protein> are rather involved in terminating <protein>NF-kappa B</protein> 's activity in the nucleus ."}1051{"id": "1050", "text": "The intracellular events that lead to the inactivation of I kappa B , i.e. the activation of NF-kappa B , are complex .", "annotated_text": "The intracellular events that lead to the inactivation of <protein>I kappa B</protein> , i.e. the activation of <protein>NF-kappa B</protein> , are complex ."}1052{"id": "1051", "text": "They involve phosphorylation and proteolytic reactions and seem to be controlled by the cells ' redox status .", "annotated_text": "They involve phosphorylation and proteolytic reactions and seem to be controlled by the cells ' redox status ."}1053{"id": "1052", "text": "Interference with the activation or activity of NF-kappa B may be beneficial in suppressing toxic/septic shock , graft-vs-host reactions , acute inflammatory reactions , acute phase response , and radiation damage .", "annotated_text": "Interference with the activation or activity of <protein>NF-kappa B</protein> may be beneficial in suppressing toxic/septic shock , graft-vs-host reactions , acute inflammatory reactions , acute phase response , and radiation damage ."}1054{"id": "1053", "text": "The inhibition of NF-kappa B activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes .", "annotated_text": "The inhibition of <protein>NF-kappa B</protein> activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes ."}1055{"id": "1054", "text": "Lack of T-cell-mediated recognition of the fusion region of the pml/RAR-alpha hybrid protein by lymphocytes of acute promyelocytic leukemia patients .", "annotated_text": "Lack of T-cell-mediated recognition of the fusion region of the <protein>pml/RAR-alpha hybrid protein</protein> by <cell_type>lymphocytes</cell_type> of acute promyelocytic leukemia patients ."}1056{"id": "1055", "text": "In previous studies , it was shown that the fusion region of the pml/RAR-alpha protein , expressed by acute promyelocytic leukemia ( APL ) cells , can be specifically recognized in vitro by donor ( D. E. ) CD4 T cells in a HLA class II DR11-restricted fashion .", "annotated_text": "In previous studies , it was shown that the fusion region of the <protein>pml/RAR-alpha protein</protein> , expressed by <cell_line>acute promyelocytic leukemia ( APL ) cells</cell_line> , can be specifically recognized in vitro by donor ( D. E. ) <cell_line>CD4 T cells</cell_line> in a <protein>HLA class II</protein> DR11-restricted fashion ."}1057{"id": "1056", "text": "We present here the results on the recognition of several pml/RAR-alpha peptides by APL patients expressing HLA DR11 .", "annotated_text": "We present here the results on the recognition of several pml/RAR-alpha peptides by APL patients expressing <protein>HLA DR11</protein> ."}1058{"id": "1057", "text": "The in vitro immunization of peripheral blood lymphocytes from four patients in remission ( S.R. , F.R. , M.M. , P. G. ) with BCR1/25 , a 25-mer pml/ RAR-alpha , did not elicit either a polyclonal or a clonal immune response specific to the peptide .", "annotated_text": "The in vitro immunization of <cell_type>peripheral blood lymphocytes</cell_type> from four patients in remission ( S.R. , F.R. , M.M. , P. G. ) with BCR1/25 , a 25-mer pml/ <protein>RAR-alpha</protein> , did not elicit either a polyclonal or a clonal immune response specific to the peptide ."}1059{"id": "1058", "text": "We then generated new donor anti-pml/RAR-alpha CD4 ( + ) T-cell clones .", "annotated_text": "We then generated new donor <cell_line>anti-pml/RAR-alpha CD4 ( + ) T-cell clones</cell_line> ."}1060{"id": "1059", "text": "These clones were tested for their recognition of BCR1/25 .", "annotated_text": "These clones were tested for their recognition of BCR1/25 ."}1061{"id": "1060", "text": "One clone ( C3/5 , CD3 ( + ) , CD4 ( + ) , CD8 ( - ) ) was selected for further analysis .", "annotated_text": "One clone ( <cell_line>C3/5 , CD3 ( + ) , CD4 ( + ) , CD8 ( - )</cell_line> ) was selected for further analysis ."}1062{"id": "1061", "text": "Clone C3/5 showed specific proliferation , cytotoxicity , and cytokine ( tumor necrosis factor alpha , granulocyte-macrophage colony-stimulating factor ) production when challenged with autologous lymphoblastic cell lines pulsed with peptide BCR1/25 .", "annotated_text": "<cell_line>Clone C3/5</cell_line> showed specific proliferation , cytotoxicity , and cytokine ( <protein>tumor necrosis factor alpha</protein> , <protein>granulocyte-macrophage colony-stimulating factor</protein> ) production when challenged with <cell_line>autologous lymphoblastic cell lines</cell_line> pulsed with peptide BCR1/25 ."}1063{"id": "1062", "text": "C3/5 cells developed specific proliferation and cytotoxicity when challenged with peptide-pulsed lymphoblastic cell lines and peripheral blood lymphocytes from the four DR11 ( + ) APL patients .", "annotated_text": "<cell_line>C3/5 cells</cell_line> developed specific proliferation and cytotoxicity when challenged with <cell_line>peptide-pulsed lymphoblastic cell lines</cell_line> and <cell_type>peripheral blood lymphocytes</cell_type> from the four DR11 ( + ) APL patients ."}1064{"id": "1063", "text": "APL blasts , available only from patients F.R. and P.G. , were not lysed by C3/5 and were unable to present peptide BCR1/25 .", "annotated_text": "<cell_type>APL blasts</cell_type> , available only from patients F.R. and P.G. , were not lysed by <cell_line>C3/5</cell_line> and were unable to present peptide BCR1/25 ."}1065{"id": "1064", "text": "Incubation of APL cells with IFN-gamma failed to induce HLA class II molecules and recognition by the C3/5 clone .", "annotated_text": "Incubation of <cell_line>APL cells</cell_line> with <protein>IFN-gamma</protein> failed to induce <protein>HLA class II molecules</protein> and recognition by the <cell_line>C3/5 clone</cell_line> ."}1066{"id": "1065", "text": "Since APL cells do not express HLA class II molecules , we tested in two donors ( D.E. and C.H.R. ) and in patients S.R.and P.G.whether the use of 9-mer peptides ( BCR1/9 ) would generate a CD8 /HLA class I -restricted response .", "annotated_text": "Since <cell_line>APL cells</cell_line> do not express <protein>HLA class II molecules</protein> , we tested in two donors ( D.E. and C.H.R. ) and in patients S.R.and P.G.whether the use of 9-mer peptides ( BCR1/9 ) would generate a <protein>CD8</protein> <protein>/HLA class I</protein> -restricted response ."}1067{"id": "1066", "text": "No peptide-specific T-cell line or clone could be generated from both donors and patients .", "annotated_text": "No <cell_line>peptide-specific T-cell line</cell_line> or clone could be generated from both donors and patients ."}1068{"id": "1067", "text": "These findings are discussed in relation to possible therapeutic approaches to the immunotherapy of APL .", "annotated_text": "These findings are discussed in relation to possible therapeutic approaches to the immunotherapy of APL ."}1069{"id": "1068", "text": "The proximal regulatory element of the interferon-gamma promoter mediates selective expression in T cells .", "annotated_text": "The proximal regulatory element of the <dna>interferon-gamma promoter</dna> mediates selective expression in <cell_type>T cells</cell_type> ."}1070{"id": "1069", "text": "Interferon-gamma ( IFN-gamma ) is produced by natural killer cells and certain subsets of T cells , but the basis for its selective expression is unknown .", "annotated_text": "<protein>Interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) is produced by <cell_type>natural killer cells</cell_type> and certain subsets of <cell_type>T cells</cell_type> , but the basis for its selective expression is unknown ."}1071{"id": "1070", "text": "Within the region between -108 and -40 base pairs of the IFN-gamma promoter are two conserved and essential regulatory elements , which confer activation-specific expression in T cells .", "annotated_text": "Within the region between -108 and -40 base pairs of the <protein>IFN-gamma</protein> promoter are two conserved and essential <dna>regulatory elements</dna> , which confer activation-specific expression in <cell_type>T cells</cell_type> ."}1072{"id": "1071", "text": "This report describes studies indicating that the most proximal of these two regulatory elements is an important determinant of its restricted expression .", "annotated_text": "This report describes studies indicating that the most proximal of these two <dna>regulatory elements</dna> is an important determinant of its restricted expression ."}1073{"id": "1072", "text": "The proximal element is a composite site that binds members of the CREB/ATF , AP-1 , and octamer families of transcription factors .", "annotated_text": "The proximal element is a composite site that binds members of the <protein>CREB/ATF</protein> , <protein>AP-1</protein> , and <protein>octamer families</protein> of <protein>transcription factors</protein> ."}1074{"id": "1073", "text": "Jun is essential for activation-induced transcription and binds preferably as a heterodimer with ATF-2 .", "annotated_text": "<protein>Jun</protein> is essential for activation-induced transcription and binds preferably as a heterodimer with <protein>ATF-2</protein> ."}1075{"id": "1074", "text": "In contrast , CREB appears to dampen transcription from this element .", "annotated_text": "In contrast , <protein>CREB</protein> appears to dampen transcription from this element ."}1076{"id": "1075", "text": "The CpG dinucleotide in this element is selectively methylated in Th2 T cells and other cells that do not express IFN-gamma , and methylation markedly reduces transcription factor binding .", "annotated_text": "The CpG dinucleotide in this <dna>element</dna> is selectively methylated in <cell_type>Th2 T cells</cell_type> and other cells that do not express <protein>IFN-gamma</protein> , and methylation markedly reduces <protein>transcription factor</protein> binding ."}1077{"id": "1076", "text": "As a target for DNA methylation and for binding of transcription factors that mediate or impede transcription , this element appears to play a central role in controlling IFN-gamma expression .", "annotated_text": "As a target for DNA methylation and for binding of <protein>transcription factors</protein> that mediate or impede transcription , this element appears to play a central role in controlling <protein>IFN-gamma</protein> expression ."}1078{"id": "1077", "text": "CD40 , but not lipopolysaccharide and anti-IgM stimulation of primary B lymphocytes , leads to a persistent nuclear accumulation of RelB .", "annotated_text": "<protein>CD40</protein> , but not lipopolysaccharide and <protein>anti-IgM</protein> stimulation of <cell_type>primary B lymphocytes</cell_type> , leads to a persistent nuclear accumulation of <protein>RelB</protein> ."}1079{"id": "1078", "text": "In this study we analyzed the effect of CD40 stimulation on the activity and nuclear appearance of Rel/nuclear factor kappaB ( NF-kappaB ) factors in primary murine B lymphocytes .", "annotated_text": "In this study we analyzed the effect of <protein>CD40</protein> stimulation on the activity and nuclear appearance of <protein>Rel/nuclear factor kappaB ( NF-kappaB ) factors</protein> in <cell_type>primary murine B lymphocytes</cell_type> ."}1080{"id": "1079", "text": "We show that triggering of CD40 signaling pathway ( s ) by CD40 ligands expressed on L cells led to strong activation of an NF-kappaB-controlled beta-globin reporter gene in primary B lymphocytes from transgenic mice .", "annotated_text": "We show that triggering of <protein>CD40</protein> signaling pathway ( s ) by <protein>CD40 ligands</protein> expressed on <cell_type>L cells</cell_type> led to strong activation of an <dna>NF-kappaB-controlled beta-globin reporter gene</dna> in <cell_type>primary B lymphocytes</cell_type> from transgenic mice ."}1081{"id": "1080", "text": "Analyses of nuclear translocation of individual members of Rel proteins after CD40 induction of primary B cells showed a strong and long-lasting accumulation of RelB and , less pronounced , of c-Rel .", "annotated_text": "Analyses of nuclear translocation of individual members of <protein>Rel proteins</protein> after <protein>CD40</protein> induction of <cell_type>primary B cells</cell_type> showed a strong and long-lasting accumulation of <protein>RelB</protein> and , less pronounced , of <protein>c-Rel</protein> ."}1082{"id": "1081", "text": "LPS stimulation did not give rise to a persistent nuclear accumulation of RelB and c-Rel , whereas nuclear c-Rel , but not RelB , accumulated after B cell receptor stimulation .", "annotated_text": "LPS stimulation did not give rise to a persistent nuclear accumulation of <protein>RelB</protein> and <protein>c-Rel</protein> , whereas nuclear <protein>c-Rel</protein> , but not <protein>RelB</protein> , accumulated after B cell receptor stimulation ."}1083{"id": "1082", "text": "CD40 induced not only nuclear translocation but also de novo synthesis of RelB RNA and protein .", "annotated_text": "<protein>CD40</protein> induced not only nuclear translocation but also de novo synthesis of <rna>RelB RNA</rna> and protein ."}1084{"id": "1083", "text": "S107 plasmacytoma cells , which express CD40 but are defective for the nuclear appearance of p50/p65-NF-kappaB , do not express RelB after CD40 stimulation .", "annotated_text": "<cell_line>S107 plasmacytoma cells</cell_line> , which express <protein>CD40</protein> but are defective for the nuclear appearance of <protein>p50/p65-NF-kappaB</protein> , do not express <protein>RelB</protein> after <protein>CD40</protein> stimulation ."}1085{"id": "1084", "text": "In S107 cells stably transfected with relB genes , stimulation of nuclear RelB translocation by CD40 was observed .", "annotated_text": "In <cell_line>S107 cells</cell_line> stably transfected with <dna>relB genes</dna> , stimulation of nuclear <protein>RelB</protein> translocation by <protein>CD40</protein> was observed ."}1086{"id": "1085", "text": "These results indicate that stimulation of CD40 signaling pathways exerts a long-lasting stimulatory effect on both the transcription and nuclear translocation of RelB .", "annotated_text": "These results indicate that stimulation of <protein>CD40</protein> signaling pathways exerts a long-lasting stimulatory effect on both the transcription and nuclear translocation of <protein>RelB</protein> ."}1087{"id": "1086", "text": "Since LPS and anti-IgM were unable to activate RelB , CD40 appears to trigger a special program of gene expression involved in the proliferation and/or differentiation of B lymphocytes .", "annotated_text": "Since LPS and <protein>anti-IgM</protein> were unable to activate <protein>RelB</protein> , <protein>CD40</protein> appears to trigger a special program of gene expression involved in the proliferation and/or differentiation of <cell_type>B lymphocytes</cell_type> ."}1088{"id": "1087", "text": "Identification and characterization of a leukocyte-specific component of the nuclear body .", "annotated_text": "Identification and characterization of a leukocyte-specific component of the nuclear body ."}1089{"id": "1088", "text": "The nuclear body ( NB ) is a cellular organelle that is involved in the pathogenesis of acute promyelocytic leukemia and viral infection .", "annotated_text": "The nuclear body ( NB ) is a cellular organelle that is involved in the pathogenesis of acute promyelocytic leukemia and viral infection ."}1090{"id": "1089", "text": "The NB is also a target of antibodies in the serum of patients with the autoimmune disease primary biliary cirrhosis .", "annotated_text": "The NB is also a target of <protein>antibodies</protein> in the serum of patients with the autoimmune disease primary biliary cirrhosis ."}1091{"id": "1090", "text": "In this study , serum from a patient with primary biliary cirrhosis was used to identify a cDNA encoding a novel component of the NB , a 140-kDa protein designated Sp140 .", "annotated_text": "In this study , serum from a patient with primary biliary cirrhosis was used to identify a cDNA encoding a novel component of the NB , a <protein>140-kDa protein</protein> designated <protein>Sp140</protein> ."}1092{"id": "1091", "text": "The predicted amino acid sequence of the amino-terminal portion of Sp140 was similar to Sp100 , a previously identified NB protein .", "annotated_text": "The predicted amino acid sequence of the <protein>amino-terminal portion</protein> of <protein>Sp140</protein> was similar to <protein>Sp100</protein> , a previously identified <protein>NB protein</protein> ."}1093{"id": "1092", "text": "The carboxyl portion of Sp140 contained a zinc-finger domain and a bromodomain , motifs that are present in proteins regulating gene transcription .", "annotated_text": "The <protein>carboxyl portion</protein> of <protein>Sp140</protein> contained a <protein>zinc-finger domain</protein> and a <protein>bromodomain</protein> , motifs that are present in proteins regulating gene transcription ."}1094{"id": "1093", "text": "High levels of Sp140 mRNA were detected in human spleen and peripheral blood leukocytes , but not other human tissues .", "annotated_text": "High levels of <rna>Sp140 mRNA</rna> were detected in human spleen and <cell_type>peripheral blood leukocytes</cell_type> , but not other human tissues ."}1095{"id": "1094", "text": "The level of SP140 mRNA in myeloid precursor cell lines HL60 and NB4 markedly increased in response to chemically induced cellular differentiation .", "annotated_text": "The level of <rna>SP140 mRNA</rna> in <cell_line>myeloid precursor cell lines</cell_line> <cell_line>HL60</cell_line> and <cell_line>NB4</cell_line> markedly increased in response to chemically induced cellular differentiation ."}1096{"id": "1095", "text": "Immunohistochemical techniques were used to demonstrate that SP140 localized to the NB in differentiated HL60 and NB4 cells .", "annotated_text": "Immunohistochemical techniques were used to demonstrate that <protein>SP140</protein> localized to the NB in differentiated <cell_line>HL60</cell_line> and <cell_line>NB4 cells</cell_line> ."}1097{"id": "1096", "text": "The location of Sp140 in the NB , and expression of this gene in cells involved in host defense , suggest that Sp140 may be involved in the pathogenesis of acute promyelocytic leukemia and viral infection .", "annotated_text": "The location of <protein>Sp140</protein> in the NB , and expression of this gene in cells involved in host defense , suggest that <protein>Sp140</protein> may be involved in the pathogenesis of acute promyelocytic leukemia and viral infection ."}1098{"id": "1097", "text": "Regulation of cytokine and cytokine receptor expression by glucocorticoids .", "annotated_text": "Regulation of <protein>cytokine</protein> and <protein>cytokine receptor</protein> expression by glucocorticoids ."}1099{"id": "1098", "text": "Glucocorticoids ( GCS ) profoundly inhibit several aspects of T cell immunity largely through inhibition of cytokine expression at the transcriptional and posttranscriptional levels .", "annotated_text": "Glucocorticoids ( GCS ) profoundly inhibit several aspects of T cell immunity largely through inhibition of <protein>cytokine</protein> expression at the transcriptional and posttranscriptional levels ."}1100{"id": "1099", "text": "GCS were also reported to act indirectly by inducing transforming growth factor-beta expression , which in turn blocks T cell immunity .", "annotated_text": "GCS were also reported to act indirectly by inducing transforming <protein>growth factor-beta</protein> expression , which in turn blocks T cell immunity ."}1101{"id": "1100", "text": "In exerting their antiproliferative effects , GCS diffuse into target cells where they bind their cytoplasmic receptor , which in turn translocates to the nucleus where it inhibits transcription of cytokine genes through direct binding to the glucocorticoid response elements ( GRE ) , which are located in the promoter region of cytokine genes or , alternatively , through antagonism of the action of transcription factors required for optimal transcriptional activation .", "annotated_text": "In exerting their antiproliferative effects , GCS diffuse into <cell_type>target cells</cell_type> where they bind their <protein>cytoplasmic receptor</protein> , which in turn translocates to the nucleus where it inhibits transcription of <dna>cytokine genes</dna> through direct binding to the <dna>glucocorticoid response elements</dna> ( <dna>GRE</dna> ) , which are located in the promoter region of <dna>cytokine genes</dna> or , alternatively , through antagonism of the action of <protein>transcription factors</protein> required for optimal transcriptional activation ."}1102{"id": "1101", "text": "In contrast to their inhibitory effects on cytokine expression , GCS up-regulate cytokine receptor expression that correlates with enhanced cytokine effects on target cells .", "annotated_text": "In contrast to their inhibitory effects on <protein>cytokine</protein> expression , GCS up-regulate <protein>cytokine receptor</protein> expression that correlates with enhanced <protein>cytokine</protein> effects on <cell_type>target cells</cell_type> ."}1103{"id": "1102", "text": "In this review , we summarize the current state of knowledge of the mechanism of action of GCS , including the phenomenon of steroid-induced rebound , which ensues upon GCS withdrawal .", "annotated_text": "In this review , we summarize the current state of knowledge of the mechanism of action of GCS , including the phenomenon of steroid-induced rebound , which ensues upon GCS withdrawal ."}1104{"id": "1103", "text": "Isolation and characterization of murine fra-1 : induction mediated by CD40 and surface Ig is protein kinase C dependent .", "annotated_text": "Isolation and characterization of <dna>murine fra-1</dna> : induction mediated by <protein>CD40</protein> and <protein>surface Ig</protein> is <protein>protein kinase C</protein> dependent ."}1105{"id": "1104", "text": "The murine fra-1 gene , encoding Fos-related Ag 1 , was isolated from a splenic cDNA library and sequenced .", "annotated_text": "The <dna>murine fra-1 gene</dna> , encoding <protein>Fos-related Ag 1</protein> , was isolated from a <dna>splenic cDNA library</dna> and sequenced ."}1106{"id": "1105", "text": "Murine fra-1 was highly homologous to rat and human fra-1 .", "annotated_text": "<dna>Murine fra-1</dna> was highly homologous to <dna>rat and human fra-1</dna> ."}1107{"id": "1106", "text": "Oligonucleotide primers based on the murine sequence were used to construct a quantitative reverse transcription-PCR assay for gene expression .", "annotated_text": "Oligonucleotide primers based on the <dna>murine sequence</dna> were used to construct a quantitative reverse transcription-PCR assay for gene expression ."}1108{"id": "1107", "text": "B lymphocyte stimulation via both CD40 and surface Ig ( sIg ) receptors substantially induced fra-1 expression , and for both receptors , induction was protein kinase C ( PKC ) dependent .", "annotated_text": "<cell_type>B lymphocyte</cell_type> stimulation via both <protein>CD40</protein> and <protein>surface Ig ( sIg ) receptors</protein> substantially induced <dna>fra-1</dna> expression , and for both receptors , induction was <protein>protein kinase C</protein> ( <protein>PKC</protein> ) dependent ."}1109{"id": "1108", "text": "This contrasts with induction of c-fos by both CD40 and sIg , which is PKC independent and indicates that CD40 is capable of signaling through PKC or a closely related kinase .", "annotated_text": "This contrasts with induction of <dna>c-fos</dna> by both <protein>CD40</protein> and <protein>sIg</protein> , which is <protein>PKC</protein> independent and indicates that <protein>CD40</protein> is capable of signaling through <protein>PKC</protein> or a closely related <protein>kinase</protein> ."}1110{"id": "1109", "text": "Induction of fra-1 following engagement of CD40 did not require protein synthesis , suggesting that the PKC -dependent linkage between CD40 and fra-1 is direct .", "annotated_text": "Induction of <dna>fra-1</dna> following engagement of <protein>CD40</protein> did not require protein synthesis , suggesting that the <protein>PKC</protein> -dependent linkage between <protein>CD40</protein> and <dna>fra-1</dna> is direct ."}1111{"id": "1110", "text": "CD40 -mediated fra-1 induction did require tyrosine kinase activity .", "annotated_text": "<protein>CD40</protein> -mediated <dna>fra-1</dna> induction did require <protein>tyrosine kinase</protein> activity ."}1112{"id": "1111", "text": "These results demonstrate that CD40 , like sIg , may employ PKC in producing select outcomes , that individual B cell receptors may signal downstream events via both PKC-dependent and PKC-independent pathways , and that multiple signal transduction pathways may be used to activate the expression of closely related genes .", "annotated_text": "These results demonstrate that <protein>CD40</protein> , like <protein>sIg</protein> , may employ <protein>PKC</protein> in producing select outcomes , that individual <protein>B cell receptors</protein> may signal downstream events via both PKC-dependent and PKC-independent pathways , and that multiple signal transduction pathways may be used to activate the expression of closely related <dna>genes</dna> ."}1113{"id": "1112", "text": "Pentoxifylline for the treatment of infection with human immunodeficiency virus .", "annotated_text": "Pentoxifylline for the treatment of infection with human immunodeficiency virus ."}1114{"id": "1113", "text": "Cytokine dysregulation in human immunodeficiency virus type 1 ( HIV-1 ) infection has been documented in numerous studies and has been cited as an important component in the pathogenesis of this retroviral infection .", "annotated_text": "Cytokine dysregulation in human immunodeficiency virus type 1 ( HIV-1 ) infection has been documented in numerous studies and has been cited as an important component in the pathogenesis of this retroviral infection ."}1115{"id": "1114", "text": "Pharmacological modification of cytokine dysregulation , therefore , has been suggested as a therapeutic modality for HIV-1 infection .", "annotated_text": "Pharmacological modification of <protein>cytokine</protein> dysregulation , therefore , has been suggested as a therapeutic modality for HIV-1 infection ."}1116{"id": "1115", "text": "Dr. Dezube of Beth Israel Hospital ( Boston ) concisely reviews the state of our knowledge regarding the effects of pentoxifylline on expression of tumor necrosis factor-alpha , a cytokine known to influence HIV-1 replication and to play a possible role in the clinical manifestations of advanced infection with this virus .", "annotated_text": "Dr. Dezube of Beth Israel Hospital ( Boston ) concisely reviews the state of our knowledge regarding the effects of pentoxifylline on expression of <protein>tumor necrosis factor-alpha</protein> , a <protein>cytokine</protein> known to influence HIV-1 replication and to play a possible role in the clinical manifestations of advanced infection with this virus ."}1117{"id": "1116", "text": "Pentoxifylline , a trisubstituted xanthine derivative , has been used to decrease blood viscosity and is reasonably well tolerated by most recipients of the drug .", "annotated_text": "Pentoxifylline , a trisubstituted xanthine derivative , has been used to decrease blood viscosity and is reasonably well tolerated by most recipients of the drug ."}1118{"id": "1117", "text": "Results of preliminary studies , many of which were conducted by Dr. Dezube , suggest that use of this agent in combination with antiretroviral compounds may prove useful in the treatment of patients with HIV-1 infection .", "annotated_text": "Results of preliminary studies , many of which were conducted by Dr. Dezube , suggest that use of this agent in combination with antiretroviral compounds may prove useful in the treatment of patients with HIV-1 infection ."}1119{"id": "1118", "text": "Activation of the granulocyte-macrophage colony-stimulating factor promoter in T cells requires cooperative binding of Elf-1 and AP-1 transcription factors .", "annotated_text": "Activation of the <dna>granulocyte-macrophage colony-stimulating factor promoter</dna> in <cell_type>T cells</cell_type> requires cooperative binding of <protein>Elf-1</protein> and <protein>AP-1</protein> <protein>transcription factors</protein> ."}1120{"id": "1119", "text": "The granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene has been studied extensively as a model system of transcriptional induction during T-lymphocyte activation .", "annotated_text": "The <dna>granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene</dna> has been studied extensively as a model system of transcriptional induction during T-lymphocyte activation ."}1121{"id": "1120", "text": "The GM-CSF gene is not expressed in resting peripheral blood T cells but is rapidly induced at the transcriptional level following activation through the cell surface T-cell receptor .", "annotated_text": "The <dna>GM-CSF gene</dna> is not expressed in <cell_type>resting peripheral blood T cells</cell_type> but is rapidly induced at the transcriptional level following activation through the <protein>cell surface T-cell receptor</protein> ."}1122{"id": "1121", "text": "A highly conserved 19-bp element located immediately 5 ' of the human GM-CSF TATA box ( bp -34 to -52 ) , herein called purine box 1 ( PB1 ) , has been shown to bind a T-cell nuclear protein complex and to be required for transcriptional induction of the GM-CSF gene following T-cell activation .", "annotated_text": "A highly conserved 19-bp element located immediately 5 ' of the <dna>human GM-CSF TATA box</dna> ( <dna>bp -34 to -52</dna> ) , herein called <dna>purine box 1</dna> ( <dna>PB1</dna> ) , has been shown to bind a <protein>T-cell nuclear protein complex</protein> and to be required for transcriptional induction of the <dna>GM-CSF gene</dna> following T-cell activation ."}1123{"id": "1122", "text": "The PB1 sequence motif is highly conserved in both human and murine GM-CSF genes .", "annotated_text": "The <dna>PB1</dna> sequence motif is highly conserved in both <dna>human and murine GM-CSF genes</dna> ."}1124{"id": "1123", "text": "In this report , we demonstrate that the PB1 element alone confers inducibility on a heterologous promoter following transfection into human Jurkat T cells .", "annotated_text": "In this report , we demonstrate that the <dna>PB1 element</dna> alone confers inducibility on a heterologous promoter following transfection into <cell_line>human Jurkat T cells</cell_line> ."}1125{"id": "1124", "text": "In addition , we identify a major PB1 nuclear protein-binding complex that is not present in resting peripheral blood T cells but is rapidly induced following T-cell activation .", "annotated_text": "In addition , we identify a major <protein>PB1 nuclear protein-binding complex</protein> that is not present in <cell_type>resting peripheral blood T cells</cell_type> but is rapidly induced following T-cell activation ."}1126{"id": "1125", "text": "Sequence analysis revealed that PB1 is composed of adjacent binding sites for Ets and AP-1 transcription factors .", "annotated_text": "Sequence analysis revealed that <dna>PB1</dna> is composed of <dna>adjacent binding sites</dna> for <protein>Ets</protein> and <protein>AP-1</protein> <protein>transcription factors</protein> ."}1127{"id": "1126", "text": "In vitro mutagenesis experiments demonstrated that both the Ets and AP-1 sites are required for binding of the inducible PB1 nuclear protein complex and for the transcriptional activity of this element and the GM-CSF promoter in activated T cells .", "annotated_text": "In vitro mutagenesis experiments demonstrated that both the <dna>Ets and AP-1 sites</dna> are required for binding of the inducible <protein>PB1 nuclear protein complex</protein> and for the transcriptional activity of this element and the <dna>GM-CSF promoter</dna> in <cell_type>activated T cells</cell_type> ."}1128{"id": "1127", "text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"}1129{"id": "1128", "text": "Steroid-resistant asthma .", "annotated_text": "Steroid-resistant asthma ."}1130{"id": "1129", "text": "Cellular mechanisms contributing to inadequate response to glucocorticoid therapy .", "annotated_text": "Cellular mechanisms contributing to inadequate response to glucocorticoid therapy ."}1131{"id": "1130", "text": "The current study examined whether alterations in glucocorticoid receptor ( GR ) binding contribute to poor response to glucocorticoid therapy in asthma .", "annotated_text": "The current study examined whether alterations in <protein>glucocorticoid receptor</protein> ( <protein>GR</protein> ) binding contribute to poor response to glucocorticoid therapy in asthma ."}1132{"id": "1131", "text": "29 asthma patients with forced expiratory volume in 1 s ( FEV1 ) < 70 % predicted were studied .", "annotated_text": "29 asthma patients with forced expiratory volume in 1 s ( FEV1 ) < 70 % predicted were studied ."}1133{"id": "1132", "text": "Patients were classified as steroid sensitive ( SS ) if their morning FEV1 increased > 30 % after a 1-wk course of oral prednisone 20 mg twice daily and steroid resistant ( SR ) if they failed to increase > 15 % .", "annotated_text": "Patients were classified as steroid sensitive ( SS ) if their morning FEV1 increased > 30 % after a 1-wk course of oral prednisone 20 mg twice daily and steroid resistant ( SR ) if they failed to increase > 15 % ."}1134{"id": "1133", "text": "PBMC obtained from these two groups , 17 SR and 12 SS , as well as 12 normal controls were analyzed. SR patients had two distinguishable GR binding abnormalities : 15 of the 17 SR patients demonstrated a significantly reduced GR binding affinity , as compared with SS patients ( P = 0.0001 ) and normal controls ( P = 0.0001 ) .", "annotated_text": "PBMC obtained from these two groups , 17 SR and 12 SS , as well as 12 normal controls were analyzed. SR patients had two distinguishable <protein>GR</protein> binding abnormalities : 15 of the 17 SR patients demonstrated a significantly reduced <protein>GR</protein> binding affinity , as compared with SS patients ( P = 0.0001 ) and normal controls ( P = 0.0001 ) ."}1135{"id": "1134", "text": "This defect was localized to T cells and reverted to normal after 48 h in culture media .", "annotated_text": "This defect was localized to <cell_type>T cells</cell_type> and reverted to normal after 48 h in culture media ."}1136{"id": "1135", "text": "However , incubation with a combination of IL-2 and IL-4 sustained this abnormality .", "annotated_text": "However , incubation with a combination of <protein>IL-2</protein> and <protein>IL-4</protein> sustained this abnormality ."}1137{"id": "1136", "text": "The other two SR patients had an abnormally low GR number with normal binding affinity that was not limited to T cells .", "annotated_text": "The other two SR patients had an abnormally low <protein>GR</protein> number with normal binding affinity that was not limited to <cell_type>T cells</cell_type> ."}1138{"id": "1137", "text": "Furthermore , GR number failed to normalize after incubation in media alone or IL-2 and IL-4 .", "annotated_text": "Furthermore , <protein>GR</protein> number failed to normalize after incubation in media alone or <protein>IL-2</protein> and <protein>IL-4</protein> ."}1139{"id": "1138", "text": "Therefore , SR asthma may be due to more than one abnormality , the majority related to a reversible cytokine -induced reduction in GR binding affinity and the second related to an irreversible reduction in GR number .", "annotated_text": "Therefore , SR asthma may be due to more than one abnormality , the majority related to a reversible <protein>cytokine</protein> -induced reduction in <protein>GR</protein> binding affinity and the second related to an irreversible reduction in <protein>GR</protein> number ."}1140{"id": "1139", "text": "These findings may have important implications for the design of alternative treatment approaches for recalcitrant asthma .", "annotated_text": "These findings may have important implications for the design of alternative treatment approaches for recalcitrant asthma ."}1141{"id": "1140", "text": "Prevalence of aneuploidy , overexpressed ER , and overexpressed EGFR in random breast aspirates of women at high and low risk for breast cancer .", "annotated_text": "Prevalence of aneuploidy , overexpressed <protein>ER</protein> , and overexpressed <protein>EGFR</protein> in random breast aspirates of women at high and low risk for breast cancer ."}1142{"id": "1141", "text": "Breast tissue biomarkers which accurately predict breast cancer development within a 10 year period in high risk women are needed but currently not available .", "annotated_text": "Breast tissue biomarkers which accurately predict breast cancer development within a 10 year period in high risk women are needed but currently not available ."}1143{"id": "1142", "text": "We initiated this study to determine 1 ) the prevalence of one or more breast tissue abnormalities in a group of women at high risk for breast cancer , and 2 ) if the prevalence of biomarker abnormalities is greater in high risk than in low risk women .", "annotated_text": "We initiated this study to determine 1 ) the prevalence of one or more breast tissue abnormalities in a group of women at high risk for breast cancer , and 2 ) if the prevalence of biomarker abnormalities is greater in high risk than in low risk women ."}1144{"id": "1143", "text": "Eligible high risk women were those with a first degree relative with breast cancer , prior breast cancer , or precancerous mastopathy .", "annotated_text": "Eligible high risk women were those with a first degree relative with breast cancer , prior breast cancer , or precancerous mastopathy ."}1145{"id": "1144", "text": "Low risk women were those without these or other major identifiable risk factors .", "annotated_text": "Low risk women were those without these or other major identifiable risk factors ."}1146{"id": "1145", "text": "Ductal cells were obtained via random fine needle aspirations and cytologically classified .", "annotated_text": "<cell_type>Ductal cells</cell_type> were obtained via random fine needle aspirations and cytologically classified ."}1147{"id": "1146", "text": "Biomarkers included DNA ploidy , estrogen receptor ( ER ) , and epidermal growth factor receptor ( EGFR ) .", "annotated_text": "Biomarkers included DNA ploidy , <protein>estrogen receptor</protein> ( <protein>ER</protein> ) , and <protein>epidermal growth factor receptor</protein> ( <protein>EGFR</protein> ) ."}1148{"id": "1147", "text": "The prevalence of DNA aneuploidy was 30 % , overexpression of ER 10 % , and overexpression of EGFR 35 % , in the 206 high risk women whose median 10 year Gail risk ( projected probability ) of developing breast cancer was 4.5 % .", "annotated_text": "The prevalence of DNA aneuploidy was 30 % , overexpression of <protein>ER</protein> 10 % , and overexpression of <protein>EGFR</protein> 35 % , in the 206 high risk women whose median 10 year Gail risk ( projected probability ) of developing breast cancer was 4.5 % ."}1149{"id": "1148", "text": "The prevalence of aneuploidy and overexpressed EGFR was significantly higher in the high risk women than in the 25 low risk controls ( p < 0.002 ) , whose median 10 year Gail risk was 0.7 % .", "annotated_text": "The prevalence of aneuploidy and overexpressed <protein>EGFR</protein> was significantly higher in the high risk women than in the 25 low risk controls ( p < 0.002 ) , whose median 10 year Gail risk was 0.7 % ."}1150{"id": "1149", "text": "The difference in the prevalence of ER overexpression between high and low risk groups was not statistically significant ( p = 0.095 ) .", "annotated_text": "The difference in the prevalence of <protein>ER</protein> overexpression between high and low risk groups was not statistically significant ( p = 0.095 ) ."}1151{"id": "1150", "text": "This may be due to the low prevalence of overexpressed ER and the small number of controls .", "annotated_text": "This may be due to the low prevalence of overexpressed <protein>ER</protein> and the small number of controls ."}1152{"id": "1151", "text": "A significant difference was noted in the prevalence of one or more abnormal biomarkers between the high risk and low risk women ( p < 0.001 ) .", "annotated_text": "A significant difference was noted in the prevalence of one or more abnormal biomarkers between the high risk and low risk women ( p < 0.001 ) ."}1153{"id": "1152", "text": "A large prospective trial is needed to determine if one or more of these biomarkers , is predictive of breast cancer development .", "annotated_text": "A large prospective trial is needed to determine if one or more of these biomarkers , is predictive of breast cancer development ."}1154{"id": "1153", "text": "Inhibition of nuclear factor kappa B subunit p65 mRNA accumulation in lipopolysaccharide-stimulated human monocytic cells treated with sodium salicylate .", "annotated_text": "Inhibition of <rna>nuclear factor kappa B subunit p65 mRNA</rna> accumulation in <cell_line>lipopolysaccharide-stimulated human monocytic cells</cell_line> treated with sodium salicylate ."}1155{"id": "1154", "text": "Lipopolysaccharide is one of the most potent trigger substances for monocytes and macrophages causing secretion of inflammatory mediators such as tumor necrosis factor and interleukin-1 .", "annotated_text": "Lipopolysaccharide is one of the most potent trigger substances for monocytes and macrophages causing secretion of <protein>inflammatory mediators</protein> such as <protein>tumor necrosis factor</protein> and <protein>interleukin-1</protein> ."}1156{"id": "1155", "text": "The nature of the nuclear factors involved in regulation of these cytokine genes is still unknown .", "annotated_text": "The nature of the nuclear factors involved in regulation of these <dna>cytokine genes</dna> is still unknown ."}1157{"id": "1156", "text": "Nuclear factor kappa B ( NF-kappa B ; heterodimer of p50 and p65 ) proteins have been suggested to play an important role in gene transcription of inflammatory mediators when monocytes are stimulated with lipopolysaccharide .", "annotated_text": "<protein>Nuclear factor kappa B ( NF-kappa B ; heterodimer of p50 and p65 ) proteins</protein> have been suggested to play an important role in gene transcription of <protein>inflammatory mediators</protein> when <cell_type>monocytes</cell_type> are stimulated with lipopolysaccharide ."}1158{"id": "1157", "text": "Nonsteroidal anti-inflammatory drugs such as salicylates have been used to treat symptoms of inflammation , and a new mechanism of drug action was suggested recently .", "annotated_text": "Nonsteroidal anti-inflammatory drugs such as salicylates have been used to treat symptoms of inflammation , and a new mechanism of drug action was suggested recently ."}1159{"id": "1158", "text": "Salicylates have been shown to inhibit lipopolysaccharide-induced gene transcription via inhibition of NF-kappa B activation by preventing the degradation of NF-kappa B inhibitor `` I kappa B `` , blocking the translocation of NF-kappa B into the nuclear compartment .", "annotated_text": "Salicylates have been shown to inhibit lipopolysaccharide-induced gene transcription via inhibition of <protein>NF-kappa B</protein> activation by preventing the degradation of <protein>NF-kappa B inhibitor</protein> `` <protein>I kappa B</protein> `` , blocking the translocation of <protein>NF-kappa B</protein> into the nuclear compartment ."}1160{"id": "1159", "text": "However , the nature of the subunit involved in this mechanism has not been defined .", "annotated_text": "However , the nature of the subunit involved in this mechanism has not been defined ."}1161{"id": "1160", "text": "To examine the mechanisms by which salicylates affect cytokine gene transcription , the amount of active and inactive NF-kappa B and NF-kappa B mRNA , in Porphyromonas gingivalis lipopolysaccharide-stimulated human monocytic cells was assessed .", "annotated_text": "To examine the mechanisms by which salicylates affect <protein>cytokine</protein> gene transcription , the amount of active and inactive <protein>NF-kappa B</protein> and <rna>NF-kappa B mRNA</rna> , in Porphyromonas gingivalis <cell_line>lipopolysaccharide-stimulated human monocytic cells</cell_line> was assessed ."}1162{"id": "1161", "text": "High doses of sodium salicylate suppressed NF-kappa B p65 mRNA accumulation , resulting in suppression of total NF-kappa B , p50 on tissue oligonucleotide had no effects on lipopolysaccharide-induced NF-kappa B activation .", "annotated_text": "High doses of sodium salicylate suppressed <protein>NF-kappa B</protein> <rna>p65 mRNA</rna> accumulation , resulting in suppression of total <protein>NF-kappa B</protein> , <protein>p50</protein> on tissue oligonucleotide had no effects on lipopolysaccharide-induced <protein>NF-kappa B</protein> activation ."}1163{"id": "1162", "text": "The data demonstrate that the p65 subunit of NF-kappa B is inhibited by salicylate treatment and highlight the role of salicylate in the control of gene expression of inflammatory mediators .", "annotated_text": "The data demonstrate that the <protein>p65</protein> subunit of <protein>NF-kappa B</protein> is inhibited by salicylate treatment and highlight the role of salicylate in the control of gene expression of <protein>inflammatory mediators</protein> ."}1164{"id": "1163", "text": "Glucocorticoid-mediated inhibition of RANTES expression in human T lymphocytes .", "annotated_text": "Glucocorticoid-mediated inhibition of <protein>RANTES</protein> expression in <cell_type>human T lymphocytes</cell_type> ."}1165{"id": "1164", "text": "The chemokine RANTES has been implicated in the pathogenesis of allergic inflammatory diseases including asthma and rhinitis which are frequently treated with glucocorticoids .", "annotated_text": "The <protein>chemokine</protein> <protein>RANTES</protein> has been implicated in the pathogenesis of allergic inflammatory diseases including asthma and rhinitis which are frequently treated with glucocorticoids ."}1166{"id": "1165", "text": "We observed that dexamethasone dramatically inhibited RANTES mRNA expression dose dependently in anti-CD3 activated Hut-78 T cells and human PBMCs .", "annotated_text": "We observed that dexamethasone dramatically inhibited <rna>RANTES mRNA</rna> expression dose dependently in <cell_line>anti-CD3 activated Hut-78 T cells</cell_line> and <cell_type>human PBMCs</cell_type> ."}1167{"id": "1166", "text": "Inhibition of RANTES expression did not appear to be secondary to IL-2 inhibition and required binding to the intracellular glucocorticoid receptor .", "annotated_text": "Inhibition of <protein>RANTES</protein> expression did not appear to be secondary to <protein>IL-2</protein> inhibition and required binding to the intracellular <protein>glucocorticoid receptor</protein> ."}1168{"id": "1167", "text": "The down-regulation of RANTES expression by glucocorticoids in T cells may directly contribute to the efficacy of these agents in suppressing cellular infiltration and to their anti-inflammatory properties .", "annotated_text": "The down-regulation of <protein>RANTES</protein> expression by glucocorticoids in <cell_type>T cells</cell_type> may directly contribute to the efficacy of these agents in suppressing cellular infiltration and to their anti-inflammatory properties ."}1169{"id": "1168", "text": "Association of TRAF1 , TRAF2 , and TRAF3 with an Epstein-Barr virus LMP1 domain important for B-lymphocyte transformation : role in NF-kappaB activation .", "annotated_text": "Association of <protein>TRAF1</protein> , <protein>TRAF2</protein> , and <protein>TRAF3</protein> with an <dna>Epstein-Barr virus LMP1 domain</dna> important for <cell_type>B-lymphocyte</cell_type> transformation : role in <protein>NF-kappaB</protein> activation ."}1170{"id": "1169", "text": "The Epstein-Barr virus ( EBV ) transforming protein LMP1 appears to be a constitutively activated tumor necrosis factor receptor ( TNFR ) on the basis of an intrinsic ability to aggregate in the plasma membrane and an association of its cytoplasmic carboxyl terminus ( CT ) with TNFR-associated factors ( TRAFs ) .", "annotated_text": "The <protein>Epstein-Barr virus ( EBV ) transforming protein LMP1</protein> appears to be a <protein>constitutively activated tumor necrosis factor receptor</protein> ( <protein>TNFR</protein> ) on the basis of an intrinsic ability to aggregate in the plasma membrane and an association of its <protein>cytoplasmic carboxyl terminus</protein> ( <protein>CT</protein> ) with <protein>TNFR-associated factors</protein> ( <protein>TRAFs</protein> ) ."}1171{"id": "1170", "text": "We now show that in EBV-transformed B lymphocytes most of TRAF1 or TRAF3 and 5 % of TRAF2 are associated with LMP1 and that most of LMP1 is associated with TRAF1 or TRAF3 .", "annotated_text": "We now show that in <cell_line>EBV-transformed B lymphocytes</cell_line> most of <protein>TRAF1</protein> or <protein>TRAF3</protein> and 5 % of <protein>TRAF2</protein> are associated with <protein>LMP1</protein> and that most of <protein>LMP1</protein> is associated with <protein>TRAF1</protein> or <protein>TRAF3</protein> ."}1172{"id": "1171", "text": "TRAF1 , TRAF2 , and TRAF3 bind to a single site in the LMP1 CT corresponding to amino acids ( aa ) 199 to 214 , within a domain which is important for B-lymphocyte growth transformation ( aa 187 to 231 ) .", "annotated_text": "<protein>TRAF1</protein> , <protein>TRAF2</protein> , and <protein>TRAF3</protein> bind to a single site in the <protein>LMP1 CT</protein> corresponding to amino acids ( aa ) 199 to 214 , within a domain which is important for B-lymphocyte growth transformation ( aa 187 to 231 ) ."}1173{"id": "1172", "text": "Further deletional and alanine mutagenesis analyses and comparison with TRAF binding sequences in CD40 , in CD30 , and in the LMP1 of other lymphycryptoviruses provide the first evidence that PXQXT/S is a core TRAF binding motif .", "annotated_text": "Further deletional and alanine mutagenesis analyses and comparison with <dna>TRAF binding sequences</dna> in CD40 , in CD30 , and in the <protein>LMP1</protein> of other lymphycryptoviruses provide the first evidence that <dna>PXQXT/S</dna> is a core <dna>TRAF binding motif</dna> ."}1174{"id": "1173", "text": "The negative effects of point mutations in the LMP1 ( 1-231 ) core TRAF binding motif on TRAF binding and NF-kappaB activation genetically link the TRAFs to LMP1 ( 1-231 ) -mediated NF-kappaB activation .", "annotated_text": "The negative effects of point mutations in the <dna>LMP1 ( 1-231 ) core TRAF binding motif</dna> on TRAF binding and <protein>NF-kappaB</protein> activation genetically link the <protein>TRAFs</protein> to <protein>LMP1</protein> ( 1-231 ) -mediated <protein>NF-kappaB</protein> activation ."}1175{"id": "1174", "text": "NF-kappaB activation by LMP1 ( 1-231 ) is likely to be mediated by TRAF1 /TRAF2 heteroaggregates since TRAF1 is unique among the TRAFs in coactivating NF-kappaB with LMP1 ( 1-231 ) , a TRAF2 dominant-negative mutant can block LMP1 ( 1-231 ) -mediated NF-kappaB activation as well as TRAF1 coactivation , and 30 % of TRAF2 is associated with TRAF1 in EBV-transformed B cells .", "annotated_text": "<protein>NF-kappaB</protein> activation by <protein>LMP1</protein> ( 1-231 ) is likely to be mediated by <protein>TRAF1</protein> <protein>/TRAF2</protein> heteroaggregates since <protein>TRAF1</protein> is unique among the <protein>TRAFs</protein> in coactivating <protein>NF-kappaB</protein> with <protein>LMP1</protein> ( 1-231 ) , a <protein>TRAF2</protein> dominant-negative mutant can block <protein>LMP1</protein> ( 1-231 ) -mediated <protein>NF-kappaB</protein> activation as well as <protein>TRAF1</protein> coactivation , and 30 % of <protein>TRAF2</protein> is associated with <protein>TRAF1</protein> in EBV-transformed B cells ."}1176{"id": "1175", "text": "TRAF3 is a negative modulator of LMP1 ( 1-231 ) -mediated NF-kappaB activation .", "annotated_text": "<protein>TRAF3</protein> is a negative modulator of <protein>LMP1</protein> ( 1-231 ) -mediated <protein>NF-kappaB</protein> activation ."}1177{"id": "1176", "text": "Surprisingly , TRAF1 , -2 , or -3 does not interact with the terminal LMP1 CT aa 333 to 386 which can independently mediate NF-kappaB activation .", "annotated_text": "Surprisingly , <protein>TRAF1 , -2 , or -3</protein> does not interact with the <protein>terminal LMP1 CT</protein> aa 333 to 386 which can independently mediate <protein>NF-kappaB</protein> activation ."}1178{"id": "1177", "text": "The constitutive association of TRAFs with LMP1 through the aa 187 to 231 domain which is important in NF-kappaB activation and primary B-lymphocyte growth transformation implicates TRAF aggregation in LMP1 signaling .", "annotated_text": "The constitutive association of <protein>TRAFs</protein> with <protein>LMP1</protein> through the <protein>aa 187 to 231 domain</protein> which is important in <protein>NF-kappaB</protein> activation and primary <cell_type>B-lymphocyte</cell_type> growth transformation implicates <protein>TRAF</protein> aggregation in <protein>LMP1</protein> signaling ."}1179{"id": "1178", "text": "Lack of IL-12 signaling in human allergen-specific Th2 cells .", "annotated_text": "Lack of <protein>IL-12</protein> signaling in <cell_line>human allergen-specific Th2 cells</cell_line> ."}1180{"id": "1179", "text": "IL-12 is a powerful skewer of CD4+ T cell responses toward the Th1 phenotype by inducing IFN-gamma production in naive Th cells .", "annotated_text": "<protein>IL-12</protein> is a powerful skewer of <cell_type>CD4+ T cell</cell_type> responses toward the Th1 phenotype by inducing <protein>IFN-gamma</protein> production in <cell_line>naive Th cells</cell_line> ."}1181{"id": "1180", "text": "In the present study we addressed the question of whether IL-12 can reverse established Th2 responses into Th1/Th0 responses by inducing IFN-gamma production in memory Th2 cells .", "annotated_text": "In the present study we addressed the question of whether <protein>IL-12</protein> can reverse established Th2 responses into Th1/Th0 responses by inducing <protein>IFN-gamma</protein> production in <cell_line>memory Th2 cells</cell_line> ."}1182{"id": "1181", "text": "To this aim , allergen-specific CD4+ T cell clones ( TCC ) were generated from the peripheral blood of three atopic patients , and their cytokine profiles were analyzed .", "annotated_text": "To this aim , <cell_line>allergen-specific CD4+ T cell clones</cell_line> ( <cell_line>TCC</cell_line> ) were generated from the peripheral blood of three atopic patients , and their <protein>cytokine</protein> profiles were analyzed ."}1183{"id": "1182", "text": "The majority of these TCC exhibited a strongly polarized Th2 cytokine profile , and the production of IFN-gamma could not be induced by exogenous IL-12 .", "annotated_text": "The majority of these <cell_line>TCC</cell_line> exhibited a strongly polarized Th2 <protein>cytokine</protein> profile , and the production of <protein>IFN-gamma</protein> could not be induced by exogenous <protein>IL-12</protein> ."}1184{"id": "1183", "text": "Only those TCC with low IFN-gamma levels in the absence of IL-12 responded to IL-12 by additional enhancement of IFN-gamma production .", "annotated_text": "Only those <cell_line>TCC</cell_line> with low <protein>IFN-gamma</protein> levels in the absence of <protein>IL-12</protein> responded to <protein>IL-12</protein> by additional enhancement of <protein>IFN-gamma</protein> production ."}1185{"id": "1184", "text": "The IL-12 nonresponsiveness of the Th2 clones was further evident by the total lack of IL-12 -induced phosphorylation of STAT4 ( signal transducer and activator of transcription-4 ) , a transcription factor that is typically involved in IL-12 signaling .", "annotated_text": "The <protein>IL-12</protein> nonresponsiveness of the <cell_line>Th2 clones</cell_line> was further evident by the total lack of <protein>IL-12</protein> -induced phosphorylation of <protein>STAT4</protein> ( <protein>signal transducer and activator of transcription-4</protein> ) , a <protein>transcription factor</protein> that is typically involved in <protein>IL-12</protein> signaling ."}1186{"id": "1185", "text": "Consequently , IL-12 also failed to induce the DNA-binding activity of STAT4-containing complexes in the nuclei of these Th2 clones .", "annotated_text": "Consequently , <protein>IL-12</protein> also failed to induce the DNA-binding activity of <protein>STAT4-containing complexes</protein> in the nuclei of these <cell_line>Th2 clones</cell_line> ."}1187{"id": "1186", "text": "All TCC expressed equal levels of the low-affinity IL-12R beta1 subunit .", "annotated_text": "All <cell_line>TCC</cell_line> expressed equal levels of the <protein>low-affinity IL-12R beta1 subunit</protein> ."}1188{"id": "1187", "text": "Our results indicate that human allergen-specific Th cells with strongly polarized Th2 cytokine profiles do not respond to IL-12 and , therefore , can not be induced to produce IFN-gamma .", "annotated_text": "Our results indicate that human allergen-specific Th cells with strongly polarized Th2 <protein>cytokine</protein> profiles do not respond to <protein>IL-12</protein> and , therefore , can not be induced to produce <protein>IFN-gamma</protein> ."}1189{"id": "1188", "text": "The apparent high frequency of IL-12-nonresponsive Th cells within the allergen-specific populations in atopic patients predicts a limited skewing potential of IL-12 in the case of established Th2 responses , but only affecting newly recruited naive Th cells .", "annotated_text": "The apparent high frequency of <cell_line>IL-12-nonresponsive Th cells</cell_line> within the allergen-specific populations in atopic patients predicts a limited skewing potential of <protein>IL-12</protein> in the case of established Th2 responses , but only affecting newly recruited naive <cell_line>Th cells</cell_line> ."}1190{"id": "1189", "text": "Cloning and expression of the Epstein-Barr virus-encoded dUTPase : patients with acute , reactivated or chronic virus infection develop antibodies against the enzyme .", "annotated_text": "Cloning and expression of the <protein>Epstein-Barr virus-encoded dUTPase</protein> : patients with acute , reactivated or chronic virus infection develop <protein>antibodies</protein> against the <protein>enzyme</protein> ."}1191{"id": "1190", "text": "The gene encoding the Epstein-Barr virus ( EBV ) -specific dUTPase was amplified from virus DNA by PCR .", "annotated_text": "The gene encoding the <protein>Epstein-Barr virus ( EBV ) -specific dUTPase</protein> was amplified from <dna>virus DNA</dna> by PCR ."}1192{"id": "1191", "text": "The active enzyme was expressed in Escherichia coli and in insect cells as a non-fusion protein .", "annotated_text": "The active enzyme was expressed in Escherichia coli and in <cell_type>insect cells</cell_type> as a <protein>non-fusion protein</protein> ."}1193{"id": "1192", "text": "The protein from E. coli specifically converted dUTP to dUMP and did not react with other dNTPs or NTPs .", "annotated_text": "The protein from E. coli specifically converted dUTP to dUMP and did not react with other dNTPs or NTPs ."}1194{"id": "1193", "text": "Preliminary experiments yielded a Km value of about 0.8 microM for dUTP .", "annotated_text": "Preliminary experiments yielded a Km value of about 0.8 microM for dUTP ."}1195{"id": "1194", "text": "MAbs against the dUTPase reacted with a protein of approximately 31 kDa in 12-O-tetradecanoyl-phorbol-13-acetate ( TPA ) -stimulated B cells harbouring either type 1 or type 2 EBV .", "annotated_text": "MAbs against the <protein>dUTPase</protein> reacted with a protein of approximately 31 kDa in <cell_line>12-O-tetradecanoyl-phorbol-13-acetate ( TPA ) -stimulated B cells</cell_line> harbouring either type 1 or type 2 EBV ."}1196{"id": "1195", "text": "The protein was found in untreated cells at low levels , whereas induction of the lytic replication cycle by TPA treatment or by providing the immediate early transactivator BZLF1 in trans resulted in increased expression .", "annotated_text": "The protein was found in <cell_type>untreated cells</cell_type> at low levels , whereas induction of the lytic replication cycle by TPA treatment or by providing the <protein>immediate early transactivator</protein> <protein>BZLF1</protein> in trans resulted in increased expression ."}1197{"id": "1196", "text": "We demonstrated that the virus dUTPase isolated from EBV-infected cells is a phosphoprotein .", "annotated_text": "We demonstrated that the <protein>virus dUTPase</protein> isolated from <cell_type>EBV-infected cells</cell_type> is a <protein>phosphoprotein</protein> ."}1198{"id": "1197", "text": "The protein expressed in insect cells was used to test for the presence of specific antibodies in sera from normal , healthy carriers and from patients with various diseases .", "annotated_text": "The protein expressed in <cell_type>insect cells</cell_type> was used to test for the presence of <protein>specific antibodies</protein> in sera from normal , healthy carriers and from patients with various diseases ."}1199{"id": "1198", "text": "While the sera of EBV-negative individuals ( 0/3 ) or healthy carriers ( 0/33 ) did not contain detectable levels of antibodies , patients with mononucleosis ( 5/18 ) , chronic EBV infection ( 2/7 ) , EBV reactivation ( 7/20 ) and human immunodeficiency virus infection ( 5/24 ) showed elevated antibody titres against the enzyme .", "annotated_text": "While the sera of EBV-negative individuals ( 0/3 ) or healthy carriers ( 0/33 ) did not contain detectable levels of antibodies , patients with mononucleosis ( 5/18 ) , chronic EBV infection ( 2/7 ) , EBV reactivation ( 7/20 ) and human immunodeficiency virus infection ( 5/24 ) showed elevated antibody titres against the enzyme ."}1200{"id": "1199", "text": "This indicated that the dUTPase is expressed during EBV replication and reactivation .", "annotated_text": "This indicated that the dUTPase is expressed during EBV replication and reactivation ."}

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