automated-analytics/bionlp2004

1{"id": "0", "text": "Number of glucocorticoid receptors in lymphocytes and their sensitivity to hormone action .", "annotated_text": "Number of <protein>glucocorticoid receptors</protein> in <cell_type>lymphocytes</cell_type> and their sensitivity to hormone action ."}2{"id": "1", "text": "The study demonstrated a decreased level of glucocorticoid receptors ( GR ) in peripheral blood lymphocytes from hypercholesterolemic subjects , and an elevated level in patients with acute myocardial infarction .", "annotated_text": "The study demonstrated a decreased level of <protein>glucocorticoid receptors</protein> ( <protein>GR</protein> ) in <cell_type>peripheral blood lymphocytes</cell_type> from hypercholesterolemic subjects , and an elevated level in patients with acute myocardial infarction ."}3{"id": "2", "text": "In the lymphocytes with a high GR number , dexamethasone inhibited [ 3H ] -thymidine and [ 3H ] -acetate incorporation into DNA and cholesterol , respectively , in the same manner as in the control cells .", "annotated_text": "In the <cell_type>lymphocytes</cell_type> with a high <protein>GR</protein> number , dexamethasone inhibited [ 3H ] -thymidine and [ 3H ] -acetate incorporation into DNA and cholesterol , respectively , in the same manner as in the <cell_type>control cells</cell_type> ."}4{"id": "3", "text": "On the other hand , a decreased GR number resulted in a less efficient dexamethasone inhibition of the incorporation of labeled compounds .", "annotated_text": "On the other hand , a decreased <protein>GR</protein> number resulted in a less efficient dexamethasone inhibition of the incorporation of labeled compounds ."}5{"id": "4", "text": "These data showed that the sensitivity of lymphocytes to glucocorticoids changed only with a decrease of GR level .", "annotated_text": "These data showed that the sensitivity of <cell_type>lymphocytes</cell_type> to glucocorticoids changed only with a decrease of <protein>GR</protein> level ."}6{"id": "5", "text": "[ 1 , 25-Dihydroxyvitamin D3 receptors in lymphocytes and T- and B-lymphocyte count in patients with glomerulonephritis ]", "annotated_text": "[ <protein>1 , 25-Dihydroxyvitamin D3 receptors</protein> in <cell_type>lymphocytes</cell_type> and <cell_type>T- and B-lymphocyte</cell_type> count in patients with glomerulonephritis ]"}7{"id": "6", "text": "Content of receptors to hormonal form of vitamin D3 , 1.25 ( OH ) 2D3 , constituted 27.3 fmole/mg of protein in lymphocytes of peripheric blood of children with glomerulonephritis .", "annotated_text": "Content of receptors to hormonal form of vitamin D3 , 1.25 ( OH ) 2D3 , constituted 27.3 fmole/mg of protein in <cell_type>lymphocytes</cell_type> of peripheric blood of children with glomerulonephritis ."}8{"id": "7", "text": "In the patients concentration of total and ionized form of Ca2+ was decreased down to 2.04 mmole/L and 1.09 mmole/L , respectively , while an increase in parathormone ( PTH ) by 36 % and a distinct decrease in 25 ( OH ) D concentration ( lower than 1.25 ng/ml ) was found in blood ; content of cAMP was also decreased in lymphocytes by 33 % .", "annotated_text": "In the patients concentration of total and ionized form of Ca2+ was decreased down to 2.04 mmole/L and 1.09 mmole/L , respectively , while an increase in parathormone ( PTH ) by 36 % and a distinct decrease in 25 ( OH ) D concentration ( lower than 1.25 ng/ml ) was found in blood ; content of cAMP was also decreased in lymphocytes by 33 % ."}9{"id": "8", "text": "At the same time , total content of T lymphocytes was decreased 1.5-fold in peripheric blood .", "annotated_text": "At the same time , total content of <cell_type>T lymphocytes</cell_type> was decreased 1.5-fold in peripheric blood ."}10{"id": "9", "text": "Treatment with I-hydroxyvitamin D3 ( 1-1.5 mg daily , within 4 weeks ) led to normalization of total and ionized form of Ca2+ and of 25 ( OH ) D , but did not affect the PTH content in blood .", "annotated_text": "Treatment with I-hydroxyvitamin D3 ( 1-1.5 mg daily , within 4 weeks ) led to normalization of total and ionized form of Ca2+ and of 25 ( OH ) D , but did not affect the PTH content in blood ."}11{"id": "10", "text": "Concentration of the receptors to 1.25 ( OH ) 2D3 was elevated up to 39.7 fmole/mg after I week of the treatment , whereas it was decreased to the initial level 24.8 fmole/mg within 4 weeks ; simultaneous alteration in the cAMP content was observed in lymphocytes .", "annotated_text": "Concentration of the <protein>receptors</protein> to 1.25 ( OH ) 2D3 was elevated up to 39.7 fmole/mg after I week of the treatment , whereas it was decreased to the initial level 24.8 fmole/mg within 4 weeks ; simultaneous alteration in the cAMP content was observed in <cell_type>lymphocytes</cell_type> ."}12{"id": "11", "text": "Treatment with 1- ( OH ) D3 normalized also the T lymphocytes content in peripheric blood .", "annotated_text": "Treatment with 1- ( OH ) D3 normalized also the <cell_type>T lymphocytes</cell_type> content in peripheric blood ."}13{"id": "12", "text": "The data obtained suggest that under conditions of glomerulonephritis only high content of receptors to 1.25 ( OH ) 2D3 in lymphocytes enabled to perform the cell response to the hormone effect .", "annotated_text": "The data obtained suggest that under conditions of glomerulonephritis only high content of <protein>receptors</protein> to 1.25 ( OH ) 2D3 in <cell_type>lymphocytes</cell_type> enabled to perform the cell response to the hormone effect ."}14{"id": "13", "text": "Tumor and serum beta-2-microglobulin expression in women with breast cancer .", "annotated_text": "Tumor and serum beta-2-microglobulin expression in women with breast cancer ."}15{"id": "14", "text": "To investigate whether the tumor expression of beta-2-microglobulin ( beta 2-M ) could serve as a marker of tumor biologic behavior , the authors studied specimens of breast carcinomas from 60 consecutive female patients .", "annotated_text": "To investigate whether the <cell_type>tumor</cell_type> expression of <protein>beta-2-microglobulin</protein> ( <protein>beta 2-M</protein> ) could serve as a marker of tumor biologic behavior , the authors studied specimens of <cell_type>breast carcinomas</cell_type> from 60 consecutive female patients ."}16{"id": "15", "text": "Presence of beta 2-M was analyzed by immunohistochemistry .", "annotated_text": "Presence of <protein>beta 2-M</protein> was analyzed by immunohistochemistry ."}17{"id": "16", "text": "No significant correlations were found between tumor beta 2-M expression and several histologic attributes such as type , histologic and nuclear grades , mitotic index , necrosis , vascular invasion , and lymphocytic infiltration .", "annotated_text": "No significant correlations were found between <protein>tumor beta 2-M</protein> expression and several histologic attributes such as type , histologic and nuclear grades , mitotic index , necrosis , vascular invasion , and lymphocytic infiltration ."}18{"id": "17", "text": "Likewise , beta 2-M was not associated with markers of disease extension such as TNM , ( UICC , classification of malignant tumors ) staging and axillary lymph node involvement or with estrogen , progesterone , and glucocorticoid receptor levels .", "annotated_text": "Likewise , <protein>beta 2-M</protein> was not associated with markers of disease extension such as TNM , ( UICC , classification of <cell_type>malignant tumors</cell_type> ) staging and axillary lymph node involvement or with estrogen , progesterone , and glucocorticoid receptor levels ."}19{"id": "18", "text": "However , there was a significantly positive association between tumor beta 2-M expression and the degree of lymphocytic infiltration in the tumor tissue .", "annotated_text": "However , there was a significantly positive association between <protein>tumor beta 2-M</protein> expression and the degree of lymphocytic infiltration in the tumor tissue ."}20{"id": "19", "text": "Beta 2-M serum levels were determined by an enzyme-linked immunosorbent assay in samples from 22 of the above women .", "annotated_text": "<protein>Beta 2-M</protein> serum levels were determined by an enzyme-linked immunosorbent assay in samples from 22 of the above women ."}21{"id": "20", "text": "Although some of the highest values had been obtained in women with larger ( T4 ) primary tumors , the authors failed to detect any statistical relationship between beta 2-M expression in the tumor with serum levels or between serum beta 2-M and the above histologic , laboratory , and clinical factors .", "annotated_text": "Although some of the highest values had been obtained in women with larger ( T4 ) primary tumors , the authors failed to detect any statistical relationship between <protein>beta 2-M</protein> expression in the tumor with serum levels or between <protein>serum beta 2-M</protein> and the above histologic , laboratory , and clinical factors ."}22{"id": "21", "text": "[ Preliminary observation of level free-form E receptor levels in serum of normal childbearing-aged and pregnant women ]", "annotated_text": "[ Preliminary observation of level <protein>free-form E receptor</protein> levels in serum of normal childbearing-aged and pregnant women ]"}23{"id": "22", "text": "In 137 cases of childbearing-aged and pregnant women , free form E receptor levels ( sE ) in serum were measured by ELISA .", "annotated_text": "In 137 cases of childbearing-aged and pregnant women , <protein>free form E receptor</protein> levels ( <protein>sE</protein> ) in serum were measured by ELISA ."}24{"id": "23", "text": "The level of sE was significantly decreased during the first trimester , slightly higher in the second trimester , and recovered to normal in the third trimester .", "annotated_text": "The level of <protein>sE</protein> was significantly decreased during the first trimester , slightly higher in the second trimester , and recovered to normal in the third trimester ."}25{"id": "24", "text": "The level remained lower in 29 PIH women but appeared higher in overdue pregnancies as compared with the normal 3rd trimester range .", "annotated_text": "The level remained lower in 29 PIH women but appeared higher in overdue pregnancies as compared with the normal 3rd trimester range ."}26{"id": "25", "text": "The results indicate that there is a relationship between a change in T cell function and pregnancy .", "annotated_text": "The results indicate that there is a relationship between a change in <cell_type>T cell</cell_type> function and pregnancy ."}27{"id": "26", "text": "Kappa B-specific DNA binding proteins : role in the regulation of human interleukin-2 gene expression .", "annotated_text": "<protein>Kappa B-specific DNA binding proteins</protein> : role in the regulation of <dna>human interleukin-2 gene</dna> expression ."}28{"id": "27", "text": "Transcriptional activation of the human interleukin-2 ( IL-2 ) gene , like induction of the IL-2 receptor alpha ( IL-2R alpha ) gene and the type 1 human immunodeficiency virus ( HIV-1 ) , is shown to be modulated by a kappa B-like enhancer element .", "annotated_text": "Transcriptional activation of the <dna>human interleukin-2 ( IL-2 ) gene</dna> , like induction of the <dna>IL-2 receptor alpha ( IL-2R alpha ) gene</dna> and the type 1 human immunodeficiency virus ( HIV-1 ) , is shown to be modulated by a <protein>kappa B-like enhancer element</protein> ."}29{"id": "28", "text": "Mutation of a kappa B core sequence identified in the IL-2 promoter ( -206 to -195 ) partially inhibits both mitogen- and HTLV-I Tax-mediated activation of this transcription unit and blocks the specific binding of two inducible cellular factors .", "annotated_text": "Mutation of a <dna>kappa B core sequence</dna> identified in the <dna>IL-2 promoter</dna> ( -206 to -195 ) partially inhibits both mitogen- and HTLV-I Tax-mediated activation of this <protein>transcription unit</protein> and blocks the specific binding of two <protein>inducible cellular factors</protein> ."}30{"id": "29", "text": "These kappa B-specific proteins ( 80 to 90 and 50 to 55 kilodaltons ) similarly interact with the functional kappa B enhancer present in the IL-2R alpha promoter .", "annotated_text": "These <protein>kappa B-specific proteins</protein> ( 80 to 90 and 50 to 55 kilodaltons ) similarly interact with the functional <protein>kappa B enhancer</protein> present in the <dna>IL-2R alpha promoter</dna> ."}31{"id": "30", "text": "These data suggest that these kappa B-specific proteins have a role in the coordinate regulation of this growth factor-growth factor receptor gene system that controls T cell proliferation .", "annotated_text": "These data suggest that these <protein>kappa B-specific proteins</protein> have a role in the coordinate regulation of this growth factor-growth factor receptor gene system that controls <cell_type>T cell</cell_type> proliferation ."}32{"id": "31", "text": "Novel region within the V kappa gene promoter is responsible for tissue and stage-specific expression of immunoglobulin genes in human lymphoid neoplasms .", "annotated_text": "Novel region within the <dna>V kappa gene promoter</dna> is responsible for tissue and stage-specific expression of <dna>immunoglobulin genes</dna> in <cell_type>human lymphoid neoplasms</cell_type> ."}33{"id": "32", "text": "Immunoglobulin gene-specific transacting factors have been shown to play a role in lymphoid tissue-specific expression of immunoglobulin genes .", "annotated_text": "<protein>Immunoglobulin gene-specific transacting factors</protein> have been shown to play a role in lymphoid tissue-specific expression of <dna>immunoglobulin genes</dna> ."}34{"id": "33", "text": "The role of these factors in B-cell differentiation and stage-specific expression of these genes is , however , not fully understood .", "annotated_text": "The role of these factors in <cell_type>B-cell</cell_type> differentiation and stage-specific expression of these genes is , however , not fully understood ."}35{"id": "34", "text": "We have used a model of human lymphoid neoplasia to address this question .", "annotated_text": "We have used a model of human lymphoid neoplasia to address this question ."}36{"id": "35", "text": "Different fragments of unrearranged human variable region of immunoglobulin kappa gene ( V kappa ) were used for cell-free in vitro transcription and DNA mobility shift assays .", "annotated_text": "Different fragments of <dna>unrearranged human variable region</dna> of <dna>immunoglobulin kappa gene</dna> ( <dna>V kappa</dna> ) were used for cell-free in vitro transcription and DNA mobility shift assays ."}37{"id": "36", "text": "Previously described enhancement of in vitro transcription that was only seen with nuclear extracts derived from B-cell neoplasms corresponding to the late stages of B-cell differentiation was shown to be dependent on the actions of these factor ( s ) on the DNA region within the V kappa gene promoter .", "annotated_text": "Previously described enhancement of in vitro transcription that was only seen with nuclear extracts derived from <cell_type>B-cell neoplasms</cell_type> corresponding to the late stages of <cell_type>B-cell</cell_type> differentiation was shown to be dependent on the actions of these factor ( s ) on the DNA region within the <dna>V kappa gene promoter</dna> ."}38{"id": "37", "text": "This region is located within the 920 bp fragment located 210 bp upstream from the coding region and this fragment represents a possible novel DNA region , which plays a role in the stage- and tissue-specific expression of immunoglobulin genes .", "annotated_text": "This region is located within the 920 bp fragment located 210 bp upstream from the coding region and this fragment represents a possible novel DNA region , which plays a role in the stage- and tissue-specific expression of <dna>immunoglobulin genes</dna> ."}39{"id": "38", "text": "[ Determination of the sensitivity to glucocorticoids in vitro ]", "annotated_text": "[ Determination of the sensitivity to <protein>glucocorticoids</protein> in vitro ]"}40{"id": "39", "text": "A modified method for the determination of glucocorticoid receptors in human lymphocytes is suggested .", "annotated_text": "A modified method for the determination of <protein>glucocorticoid receptors</protein> in <cell_type>human lymphocytes</cell_type> is suggested ."}41{"id": "40", "text": "The principal distinction of the method is standardization by the lymphocyte count in a sample ( 1 mln ) and the labeled hormone concentration .", "annotated_text": "The principal distinction of the method is standardization by the <cell_type>lymphocyte</cell_type> count in a sample ( 1 mln ) and the labeled <protein>hormone</protein> concentration ."}42{"id": "41", "text": "The modification saves time and money , limits the range of the data variations , and makes use of a lesser volume of blood .", "annotated_text": "The modification saves time and money , limits the range of the data variations , and makes use of a lesser volume of blood ."}43{"id": "42", "text": "Examinations of 70 children aged 4 to 15 suffering from the nephrotic form of glomerulonephritis have made it possible to distinguish two groups of patients : with relatively high values of specific binding X = 6820.1 +/- 530.0 ( n = 30 , p = 0.95 , t = 2.04 ) , this corresponding to a clinical form of hormone -sensitive glomerulonephritis , and with relatively low values of specific binding X = 1815.2 +/- 302.8 ( n = 40 , p = 0.95 , t = 1.96 ) , that corresponds to hormone -resistant glomerulonephritis .", "annotated_text": "Examinations of 70 children aged 4 to 15 suffering from the nephrotic form of glomerulonephritis have made it possible to distinguish two groups of patients : with relatively high values of specific binding X = 6820.1 +/- 530.0 ( n = 30 , p = 0.95 , t = 2.04 ) , this corresponding to a clinical form of <protein>hormone</protein> -sensitive glomerulonephritis , and with relatively low values of specific binding X = 1815.2 +/- 302.8 ( n = 40 , p = 0.95 , t = 1.96 ) , that corresponds to <protein>hormone</protein> -resistant glomerulonephritis ."}44{"id": "43", "text": "Dynamic studies have not shown any statistically significant changes in the specific binding values .", "annotated_text": "Dynamic studies have not shown any statistically significant changes in the specific binding values ."}45{"id": "44", "text": "These results permit regarding the specific binding value as a prognostic criterion in the assessment of corticosteroid therapy ; this allows a wide employment of the described method in practical nephrology .", "annotated_text": "These results permit regarding the specific binding value as a prognostic criterion in the assessment of <protein>corticosteroid</protein> therapy ; this allows a wide employment of the described method in practical nephrology ."}46{"id": "45", "text": "Octamer-binding proteins from B or HeLa cells stimulate transcription of the immunoglobulin heavy-chain promoter in vitro .", "annotated_text": "<protein>Octamer-binding proteins</protein> from <cell_line>B or HeLa cells</cell_line> stimulate transcription of the <dna>immunoglobulin heavy-chain promoter</dna> in vitro ."}47{"id": "46", "text": "The B-cell -type specificity of the immunoglobulin ( Ig ) heavy-chain and light-chain promoters is mediated by an octanucleotide ( OCTA ) element , ATGCAAAT , that is also a functional component of other RNA polymerase II promoters , such as snRNA and histone H2B promoters .", "annotated_text": "The <cell_type>B-cell</cell_type> -type specificity of the <protein>immunoglobulin</protein> ( <protein>Ig</protein> ) heavy-chain and light-chain promoters is mediated by an <dna>octanucleotide ( OCTA ) element</dna> , ATGCAAAT , that is also a functional component of other <dna>RNA polymerase II promoters</dna> , such as snRNA and histone H2B promoters ."}48{"id": "47", "text": "Two nuclear proteins that bind specifically and with high affinity to the OCTA element have been identified .", "annotated_text": "Two <protein>nuclear proteins</protein> that bind specifically and with high affinity to the <dna>OCTA element</dna> have been identified ."}49{"id": "48", "text": "NF-A1 is present in a variety of cell types , whereas the presence of NF-A2 is essentially confined to B cells , leading to the hypothesis that NF-A2 activates cell-type-specific transcription of the Ig promoter and NF-A1 mediates the other responses of the OCTA element .", "annotated_text": "<protein>NF-A1</protein> is present in a variety of cell types , whereas the presence of <protein>NF-A2</protein> is essentially confined to <cell_type>B cells</cell_type> , leading to the hypothesis that <protein>NF-A2</protein> activates cell-type-specific transcription of the <dna>Ig promoter</dna> and <protein>NF-A1</protein> mediates the other responses of the <dna>OCTA element</dna> ."}50{"id": "49", "text": "Extracts of the B-cell line , BJA-B , contain high levels of NF-A2 and specifically transcribe Ig promoters .", "annotated_text": "Extracts of the <cell_line>B-cell line</cell_line> , <cell_line>BJA-B</cell_line> , contain high levels of <protein>NF-A2</protein> and specifically transcribe <dna>Ig promoters</dna> ."}51{"id": "50", "text": "In contrast , extracts from HeLa cells transcribed the Ig promoter poorly .", "annotated_text": "In contrast , extracts from <cell_line>HeLa cells</cell_line> transcribed the <dna>Ig promoter</dna> poorly ."}52{"id": "51", "text": "Surprisingly , addition of either affinity-enriched NF-A2 or NF-A1 to either a HeLa extract or a partially purified reaction system specifically stimulates the Ig promoter .", "annotated_text": "Surprisingly , addition of either affinity-enriched NF-A2 or NF-A1 to either a HeLa extract or a partially purified reaction system specifically stimulates the <dna>Ig promoter</dna> ."}53{"id": "52", "text": "This suggests that the constitutive OCTA-binding factor NF-A1 can activate transcription of the Ig promoter and that B-cell -specific transcription of this promoter , at least in vitro , is partially due to a quantitative difference in the amount of OCTA-binding protein .", "annotated_text": "This suggests that the constitutive <protein>OCTA-binding factor NF-A1</protein> can activate transcription of the <dna>Ig promoter</dna> and that <cell_type>B-cell</cell_type> -specific transcription of this promoter , at least in vitro , is partially due to a quantitative difference in the amount of <protein>OCTA-binding protein</protein> ."}54{"id": "53", "text": "Because NF-A1 can stimulate Ig transcription , the inability of this factor to activate in vivo the Ig promoter to the same degree as the snRNA promoters probably reflects a difference in the context of the OCTA element in these two types of promoters .", "annotated_text": "Because <protein>NF-A1</protein> can stimulate <protein>Ig</protein> transcription , the inability of this factor to activate in vivo the <dna>Ig promoter</dna> to the same degree as the <dna>snRNA promoters</dna> probably reflects a difference in the context of the <dna>OCTA element</dna> in these two types of <dna>promoters</dna> ."}55{"id": "54", "text": "Identification of a putative regulator of early T cell activation genes .", "annotated_text": "Identification of a putative regulator of <dna>early T cell activation genes</dna> ."}56{"id": "55", "text": "Molecules involved in the antigen receptor-dependent regulation of early T cell activation genes were investigated with the use of functional sequences of the T cell activation-specific enhancer of interleukin-2 ( IL-2 ) .", "annotated_text": "Molecules involved in the antigen receptor-dependent regulation of <dna>early T cell activation genes</dna> were investigated with the use of functional sequences of the <protein>T cell activation-specific enhancer</protein> of <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) ."}57{"id": "56", "text": "One of these sequences forms a protein complex , NFAT-1 , specifically with nuclear extracts of activated T cells .", "annotated_text": "One of these sequences forms a protein complex , <protein>NFAT-1</protein> , specifically with nuclear extracts of activated <cell_type>T cells</cell_type> ."}58{"id": "57", "text": "This complex appeared 10 to 25 minutes before the activation of the IL-2 gene .", "annotated_text": "This complex appeared 10 to 25 minutes before the activation of the <dna>IL-2 gene</dna> ."}59{"id": "58", "text": "Studies with inhibitors of protein synthesis indicated that the time of synthesis of the activator of the IL-2 gene in Jurkat T cells corresponds to the time of appearance of NFAT-1 .", "annotated_text": "Studies with inhibitors of protein synthesis indicated that the time of synthesis of the activator of the <dna>IL-2 gene</dna> in <cell_line>Jurkat T cells</cell_line> corresponds to the time of appearance of <protein>NFAT-1</protein> ."}60{"id": "59", "text": "NFAT-1 , or a very similar protein , bound functional sequences of the long terminal repeat ( LTR ) of the human immunodeficiency virus type 1 ; the LTR of this virus is known to be stimulated during early T cell activation .", "annotated_text": "<protein>NFAT-1</protein> , or a very similar protein , bound functional sequences of the <dna>long terminal repeat</dna> ( <dna>LTR</dna> ) of the human immunodeficiency virus type 1 ; the <dna>LTR</dna> of this virus is known to be stimulated during early <cell_type>T cell</cell_type> activation ."}61{"id": "60", "text": "The binding site for this complex activated a linked promoter after transfection into antigen receptor-activated T cells but not other cell types .", "annotated_text": "The <dna>binding site</dna> for this complex activated a linked promoter after transfection into <cell_type>antigen receptor-activated T cells</cell_type> but not other cell types ."}62{"id": "61", "text": "These characteristics suggest that NFAT-1 transmits signals initiated at the T cell antigen receptor .", "annotated_text": "These characteristics suggest that <protein>NFAT-1</protein> transmits signals initiated at the <protein>T cell antigen receptor</protein> ."}63{"id": "62", "text": "Characterization of thyroid hormone receptors in human IM-9 lymphocytes .", "annotated_text": "Characterization of <protein>thyroid hormone receptors</protein> in <cell_line>human IM-9 lymphocytes</cell_line> ."}64{"id": "63", "text": "Although putatively identified more than 10 years ago , thyroid hormone receptors in human tissues remain poorly characterized .", "annotated_text": "Although putatively identified more than 10 years ago , <protein>thyroid hormone receptors</protein> in human tissues remain poorly characterized ."}65{"id": "64", "text": "As a first step towards understanding the mechanism of thyroid hormone action in man we have characterized T3 binding sites in nuclei of the human lymphoblastoid line , IM-9 cells .", "annotated_text": "As a first step towards understanding the mechanism of thyroid hormone action in man we have characterized <protein>T3 binding sites</protein> in nuclei of the <cell_line>human lymphoblastoid line</cell_line> , <cell_line>IM-9 cells</cell_line> ."}66{"id": "65", "text": "In whole cell experiments at 37 degrees C , nuclear binding of [ 125I ] T3 was saturable ( Kd 34 +/- 6 pmol/l ) and of finite capacity ( approximately equal to 350 sites/cell ) .", "annotated_text": "In whole cell experiments at 37 degrees C , nuclear binding of <protein>[ 125I ] T3</protein> was saturable ( Kd 34 +/- 6 pmol/l ) and of finite capacity ( approximately equal to 350 sites/cell ) ."}67{"id": "66", "text": "The binding sites were extracted from a nuclear pellet by treatment with 0.4 mol/l KCl and sonication .", "annotated_text": "The <protein>binding sites</protein> were extracted from a nuclear pellet by treatment with 0.4 mol/l KCl and sonication ."}68{"id": "67", "text": "Separation of bound from free [ 125I ] T3 in the extracts was achieved using the calcium phosphate matrix , hydroxyapatite at a concentration of 0.3 ml of a 150 g/l slurry .", "annotated_text": "Separation of bound from free <protein>[ 125I ] T3</protein> in the extracts was achieved using the calcium phosphate matrix , hydroxyapatite at a concentration of 0.3 ml of a 150 g/l slurry ."}69{"id": "68", "text": "Rectilinear Scatchard plots were obtained only when the hydroxyapatite was washed with a buffer containing 0.5 % Triton X-100 .", "annotated_text": "Rectilinear Scatchard plots were obtained only when the hydroxyapatite was washed with a buffer containing 0.5 % Triton X-100 ."}70{"id": "69", "text": "Under these conditions T3 binding sites in the nuclear extracts were present at a concentration of 22.4 +/- 8.6 fmol/mg protein and showed an affinity of ( Kd , room temperature ) 140 +/- 10 pmol/l .", "annotated_text": "Under these conditions <protein>T3 binding sites</protein> in the nuclear extracts were present at a concentration of 22.4 +/- 8.6 fmol/mg protein and showed an affinity of ( Kd , room temperature ) 140 +/- 10 pmol/l ."}71{"id": "70", "text": "The same assay system was used to determine the hierarchy of affinities for a range of natural and synthetic analogues .", "annotated_text": "The same assay system was used to determine the hierarchy of affinities for a range of natural and synthetic analogues ."}72{"id": "71", "text": "Calling T3 100 , the order of potencies observed was : Triac , 500 ; 3 , 5-diiodo-3'-isopropylthyronine , 89 ; T4 , 32 ; 3 , 5-dimethyl-3'isopropylthyronine 2 ; 3 , 5-T2 , 0.7 , rT3 , 0.4 ; 3'5'-T2 , less than 0.01 .", "annotated_text": "Calling T3 100 , the order of potencies observed was : Triac , 500 ; 3 , 5-diiodo-3'-isopropylthyronine , 89 ; T4 , 32 ; 3 , 5-dimethyl-3'isopropylthyronine 2 ; 3 , 5-T2 , 0.7 , rT3 , 0.4 ; 3'5'-T2 , less than 0.01 ."}73{"id": "72", "text": "These results suggest that the T3 binding sites present in human IM-9 lymphocyte nuclei and extracts thereof are thyroid hormone receptors .", "annotated_text": "These results suggest that the <protein>T3 binding sites</protein> present in <cell_line>human IM-9 lymphocyte</cell_line> nuclei and extracts thereof are <protein>thyroid hormone receptors</protein> ."}74{"id": "73", "text": "These cells may be a useful tool to increase our understanding of human T3 receptors", "annotated_text": "These cells may be a useful tool to increase our understanding of <protein>human T3 receptors</protein>"}75{"id": "74", "text": "Definition of T-cell specific DNA-binding factors that interact with a 3'-silencer in the CD4+ T-cell gene Rpt-1 .", "annotated_text": "Definition of <protein>T-cell specific DNA-binding factors</protein> that interact with a <dna>3'-silencer</dna> in the <dna>CD4+ T-cell gene Rpt-1</dna> ."}76{"id": "75", "text": "Analysis of the region 3 ' to the CD4+ T-cell gene Rpt-1 ( encoding regulatory protein T-lymphocyte 1 ) led to the definition of a silencer element that inhibits heterologous gene expression in certain CD4+ T-cell lines but not in B-cell or non-lymphoid cell lines .", "annotated_text": "Analysis of the region 3 ' to the <dna>CD4+ T-cell gene Rpt-1</dna> ( encoding regulatory protein <protein>T-lymphocyte 1</protein> ) led to the definition of a <dna>silencer element</dna> that inhibits <dna>heterologous gene</dna> expression in certain <cell_type>CD4+ T-cell lines</cell_type> but not in <cell_type>B-cell</cell_type> or <cell_type>non-lymphoid cell lines</cell_type> ."}77{"id": "76", "text": "Functional silencer activity in vivo was associated with the presence of a specific silencer-DNA-protein complex in electrophoretic mobility shift assays with T-cell extracts .", "annotated_text": "Functional <dna>silencer</dna> activity in vivo was associated with the presence of a specific <protein>silencer-DNA-protein complex</protein> in electrophoretic mobility shift assays with <cell_type>T-cell</cell_type> extracts ."}78{"id": "77", "text": "Formation of this complex was selectively inhibited by the region in HIV-1 containing a silencer element .", "annotated_text": "Formation of this complex was selectively inhibited by the region in <dna>HIV-1</dna> containing a <dna>silencer element</dna> ."}79{"id": "78", "text": "We discuss the possibility that DNA-binding factors may coregulate HIV-1 and Rpt-1 gene expression through a common transcriptional silencer element .", "annotated_text": "We discuss the possibility that <protein>DNA-binding factors</protein> may coregulate HIV-1 and Rpt-1 gene expression through a common <dna>transcriptional silencer element</dna> ."}80{"id": "79", "text": "Congenital immunodeficiencies associated with absence of HLA class II antigens on lymphocytes result from distinct mutations in trans-acting factors .", "annotated_text": "Congenital immunodeficiencies associated with absence of <protein>HLA class II antigens</protein> on <cell_type>lymphocytes</cell_type> result from distinct mutations in <protein>trans-acting factors</protein> ."}81{"id": "80", "text": "Coordinate regulation of HLA class II gene expression during development and coinduction of class II genes by soluble factors suggests that common trans-acting factor ( s ) control expression of these genes .", "annotated_text": "Coordinate regulation of <dna>HLA class II gene</dna> expression during development and coinduction of <dna>class II genes</dna> by <protein>soluble factors</protein> suggests that common <protein>trans-acting factor</protein> ( s ) control expression of these genes ."}82{"id": "81", "text": "In B-lymphoblastoid cell lines derived from two independent class II-deficient bare lymphocyte syndrome patients , we observed a drastic decrease in transcription rates of the class II genes .", "annotated_text": "In <cell_type>B-lymphoblastoid cell lines</cell_type> derived from two independent class II-deficient bare lymphocyte syndrome patients , we observed a drastic decrease in transcription rates of the <dna>class II genes</dna> ."}83{"id": "82", "text": "When these cell lines are fused , class II genes are reexpressed , indicating that immunodeficiencies in bare lymphocyte syndrome patients are the result of two distinct mutations .", "annotated_text": "When these cell lines are fused , <dna>class II genes</dna> are reexpressed , indicating that immunodeficiencies in bare lymphocyte syndrome patients are the result of two distinct mutations ."}84{"id": "83", "text": "Further studies show that genes governing the expression of class II antigens fall into at least three complementation groups ; two of these were previously unidentified in mutant cell lines generated in vitro .", "annotated_text": "Further studies show that genes governing the expression of <protein>class II antigens</protein> fall into at least three complementation groups ; two of these were previously unidentified in <cell_line>mutant cell lines</cell_line> generated in vitro ."}85{"id": "84", "text": "In addition , we report the identification of two discrete complexes , NFX1.1 and NFX1.2 , that bind to the DRA X consensus element .", "annotated_text": "In addition , we report the identification of two discrete complexes , <protein>NFX1.1</protein> and <protein>NFX1.2</protein> , that bind to the <dna>DRA X consensus element</dna> ."}86{"id": "85", "text": "Though the mutation in at least one mutant line generated in vitro ( RJ2.2.5 ) affects products functioning via interaction with the X box , clear alterations in either NFX1.1 or NFX1.2 are not found in any of the mutant cell lines .", "annotated_text": "Though the mutation in at least one <cell_line>mutant line</cell_line> generated in vitro ( <cell_line>RJ2.2.5</cell_line> ) affects products functioning via interaction with the <dna>X box</dna> , clear alterations in either <protein>NFX1.1</protein> or <protein>NFX1.2</protein> are not found in any of the <cell_line>mutant cell lines</cell_line> ."}87{"id": "86", "text": "In vivo responsiveness to glucocorticoid correlated with glucocorticoid receptor content in peripheral blood leukocytes in normal humans .", "annotated_text": "In vivo responsiveness to glucocorticoid correlated with <protein>glucocorticoid receptor</protein> content in <cell_type>peripheral blood leukocytes</cell_type> in normal humans ."}88{"id": "87", "text": "Dexamethasone loading tests ( 0.1 mg dexamethasone/kg , iv ) were performed in 18 normal males to evaluate the individual responsiveness to glucocorticoid .", "annotated_text": "Dexamethasone loading tests ( 0.1 mg dexamethasone/kg , iv ) were performed in 18 normal males to evaluate the individual responsiveness to glucocorticoid ."}89{"id": "88", "text": "There were inter-individual differences in increase in peripheral blood polymorphonuclear leukocyte count , decrease in peripheral blood lymphocyte count , and increase in plasma free fatty acids levels after dexamethasone injection .", "annotated_text": "There were inter-individual differences in increase in <cell_type>peripheral blood polymorphonuclear leukocyte</cell_type> count , decrease in <cell_type>peripheral blood lymphocyte</cell_type> count , and increase in plasma free fatty acids levels after dexamethasone injection ."}90{"id": "89", "text": "In addition , there was a significant correlation between the maximum increase in polymorphonuclear leukocytes and the maximum decrease in lymphocytes ( r = 0.7514 , p less than 0.0003 ) .", "annotated_text": "In addition , there was a significant correlation between the maximum increase in <cell_type>polymorphonuclear leukocytes</cell_type> and the maximum decrease in <cell_type>lymphocytes</cell_type> ( r = 0.7514 , p less than 0.0003 ) ."}91{"id": "90", "text": "Simultaneous measurements of glucocorticoid receptor content by whole-cell assay revealed that glucocorticoid receptor content in polymorphonuclear leukocytes linearly correlated with that in the corresponding lymphocytes ( r = 0.9482 , p less than 0.0001 ) .", "annotated_text": "Simultaneous measurements of <protein>glucocorticoid receptor</protein> content by whole-cell assay revealed that <protein>glucocorticoid receptor</protein> content in <cell_type>polymorphonuclear leukocytes</cell_type> linearly correlated with that in the corresponding <cell_type>lymphocytes</cell_type> ( r = 0.9482 , p less than 0.0001 ) ."}92{"id": "91", "text": "There were also significant correlations between the maximum increase in polymorphonuclear leukocytes and glucocorticoid receptor content in polymorphonuclear leukocytes ( r = 0.7239 , p less than 0.0007 ) , and between the maximum decrease in lymphocytes and glucocorticoid receptor content in lymphocytes ( r = 0.7703 , p less than 0.0002 ) .", "annotated_text": "There were also significant correlations between the maximum increase in <cell_type>polymorphonuclear leukocytes</cell_type> and <protein>glucocorticoid receptor</protein> content in <cell_type>polymorphonuclear leukocytes</cell_type> ( r = 0.7239 , p less than 0.0007 ) , and between the maximum decrease in <cell_type>lymphocytes</cell_type> and <protein>glucocorticoid receptor</protein> content in <cell_type>lymphocytes</cell_type> ( r = 0.7703 , p less than 0.0002 ) ."}93{"id": "92", "text": "These results suggest that individual differences are preserved both in glucocorticoid responsiveness and in glucocorticoid receptor content in peripheral blood leukocytes in normal humans .", "annotated_text": "These results suggest that individual differences are preserved both in glucocorticoid responsiveness and in <protein>glucocorticoid receptor</protein> content in <cell_type>peripheral blood leukocytes</cell_type> in normal humans ."}94{"id": "93", "text": "Estradiol receptors in the cytosol of peripheral blood mononuclear cells in hepatitis B virus carriers treated with interferon-alpha .", "annotated_text": "Estradiol receptors in the cytosol of <cell_type>peripheral blood mononuclear cells</cell_type> in hepatitis B virus carriers treated with <protein>interferon-alpha</protein> ."}95{"id": "94", "text": "Estradiol receptors in the cytosol of peripheral blood mononuclear cells and the effects of interferon-alpha ( IFN-alpha ) on estradiol receptors were studied in asymptomatic hepatitis B virus ( HBV ) carriers , patients with chronic hepatitis B and normal controls .", "annotated_text": "<protein>Estradiol receptors</protein> in the cytosol of <cell_type>peripheral blood mononuclear cells</cell_type> and the effects of <protein>interferon-alpha</protein> ( <protein>IFN-alpha</protein> ) on <protein>estradiol receptors</protein> were studied in asymptomatic hepatitis B virus ( HBV ) carriers , patients with chronic hepatitis B and normal controls ."}96{"id": "95", "text": "The level of estradiol receptors in the cytosol of mononuclear cells was significantly lower in asymptomatic HBV carriers and patients with chronic hepatitis B , compared to normal controls .", "annotated_text": "The level of <protein>estradiol receptors</protein> in the cytosol of <cell_type>mononuclear cells</cell_type> was significantly lower in asymptomatic HBV carriers and patients with chronic hepatitis B , compared to normal controls ."}97{"id": "96", "text": "This low level of cytosol estradiol receptors in patients with chronic hepatitis B was increased by the administration of IFN-alpha .", "annotated_text": "This low level of cytosol <protein>estradiol receptors</protein> in patients with chronic hepatitis B was increased by the administration of <protein>IFN-alpha</protein> ."}98{"id": "97", "text": "In addition , when peripheral blood mononuclear cells from patients with chronic hepatitis B were incubated with IFN-alpha in vitro , the level of cytosol estradiol receptors also increased by increasing the concentration of IFN-alpha .", "annotated_text": "In addition , when <cell_type>peripheral blood mononuclear cells</cell_type> from patients with chronic hepatitis B were incubated with <protein>IFN-alpha</protein> in vitro , the level of cytosol <protein>estradiol receptors</protein> also increased by increasing the concentration of <protein>IFN-alpha</protein> ."}99{"id": "98", "text": "We previously reported that the response of mononuclear cells to estrogen is impaired in HBV carriers , and our present results suggested that this may be due to the low level of estradiol receptors in the cytosol of mononuclear cells .", "annotated_text": "We previously reported that the response of <cell_type>mononuclear cells</cell_type> to estrogen is impaired in HBV carriers , and our present results suggested that this may be due to the low level of <protein>estradiol receptors</protein> in the cytosol of <cell_type>mononuclear cells</cell_type> ."}100{"id": "99", "text": "Association of increased lytic effector cell function with high estrogen receptor levels in tumor-bearing patients with breast cancer .", "annotated_text": "Association of increased lytic effector cell function with high <protein>estrogen receptor</protein> levels in tumor-bearing patients with breast cancer ."}101{"id": "100", "text": "Tumor-bearing patients with breast cancer were assayed for their natural killer ( NK ) cell activity and for the function of activated cytotoxic T-cells , as assessed by lectin-dependent cellular cytotoxicity ( LDCC ) .", "annotated_text": "Tumor-bearing patients with breast cancer were assayed for their <cell_type>natural killer ( NK ) cell</cell_type> activity and for the function of activated <cell_type>cytotoxic T-cells</cell_type> , as assessed by lectin-dependent cellular cytotoxicity ( LDCC ) ."}102{"id": "101", "text": "Tumor-bearing patients with breast cancer had a significant increase in NK activity and in LDCC , as compared with healthy control individuals .", "annotated_text": "Tumor-bearing patients with breast cancer had a significant increase in <cell_type>NK</cell_type> activity and in LDCC , as compared with healthy control individuals ."}103{"id": "102", "text": "Although the enhanced NK cell activity and LDCC were closely associated with high levels ( greater than 31 fmol/mg ) of estrogen receptor ( ER ) content in the primary tumor , no other clinical or histologic correlation between the increase in either parameter of cytotoxic effector cell function could be found .", "annotated_text": "Although the enhanced <cell_type>NK cell</cell_type> activity and LDCC were closely associated with high levels ( greater than 31 fmol/mg ) of <protein>estrogen receptor</protein> ( <protein>ER</protein> ) content in the primary tumor , no other clinical or histologic correlation between the increase in either parameter of <cell_type>cytotoxic effector cell</cell_type> function could be found ."}104{"id": "103", "text": "Thus , ER levels greater than 31 fmol/mg might be associated with increased cytotoxic effector cell function in tumor-bearing patients with breast cancer .", "annotated_text": "Thus , <protein>ER</protein> levels greater than 31 fmol/mg might be associated with increased <cell_type>cytotoxic effector cell</cell_type> function in tumor-bearing patients with breast cancer ."}105{"id": "104", "text": "Properties of glucocorticoid receptors in Epstein-Barr virus-transformed lymphocytes from patients with familial cortisol resistance .", "annotated_text": "Properties of <protein>glucocorticoid receptors</protein> in <cell_line>Epstein-Barr virus-transformed lymphocytes</cell_line> from patients with familial cortisol resistance ."}106{"id": "105", "text": "In a previous report of two patients with familial glucocorticoid resistance due to reduced numbers of glucocorticoid receptors ( GR ) , we have shown decreased numbers of GR in peripheral mononuclear cells and cultured fibroblasts but normal affinity of GR in both patients .", "annotated_text": "In a previous report of two patients with familial glucocorticoid resistance due to reduced numbers of <protein>glucocorticoid receptors</protein> ( <protein>GR</protein> ) , we have shown decreased numbers of <protein>GR</protein> in <cell_type>peripheral mononuclear cells</cell_type> and <cell_line>cultured fibroblasts</cell_line> but normal affinity of <protein>GR</protein> in both patients ."}107{"id": "106", "text": "In this study , peripheral lymphocytes from these patients , one patient 's son and daughter , and normal subjects were transformed with Epstein-Barr virus .", "annotated_text": "In this study , <cell_type>peripheral lymphocytes</cell_type> from these patients , one patient 's son and daughter , and normal subjects were transformed with Epstein-Barr virus ."}108{"id": "107", "text": "Reduced numbers and normal affinity of GR were found in the Epstein-Barr virus-transformed lymphocytes from both patients while the son and daughter had normal numbers and affinity of GR .", "annotated_text": "Reduced numbers and normal affinity of <protein>GR</protein> were found in the <cell_line>Epstein-Barr virus-transformed lymphocytes</cell_line> from both patients while the son and daughter had normal numbers and affinity of <protein>GR</protein> ."}109{"id": "108", "text": "The thermal stability of GR and thermal activation of cytosolic receptors in both patients were found to be normal .", "annotated_text": "The thermal stability of <protein>GR</protein> and thermal activation of <protein>cytosolic receptors</protein> in both patients were found to be normal ."}110{"id": "109", "text": "Although the percentages of nuclear bound GR were similar in both patients and normal controls , the absolute amounts of nuclear bound GR of the patients were about one-half that of normal controls .", "annotated_text": "Although the percentages of nuclear bound <protein>GR</protein> were similar in both patients and normal controls , the absolute amounts of nuclear bound <protein>GR</protein> of the patients were about one-half that of normal controls ."}111{"id": "110", "text": "These abnormal properties of GR ( reduced numbers of GR ) were preserved in the transformed cells from the patients .", "annotated_text": "These abnormal properties of <protein>GR</protein> ( reduced numbers of <protein>GR</protein> ) were preserved in the <cell_line>transformed cells</cell_line> from the patients ."}112{"id": "111", "text": "Octamer transcription factors 1 and 2 each bind to two different functional elements in the immunoglobulin heavy-chain promoter .", "annotated_text": "Octamer transcription factors 1 and 2 each bind to two different <dna>functional elements</dna> in the <dna>immunoglobulin heavy-chain promoter</dna> ."}113{"id": "112", "text": "Immunoglobulin heavy-chain genes contain two conserved sequence elements 5 ' to the site of transcription initiation : the octamer ATGCAAAT and the heptamer CTCATGA .", "annotated_text": "<dna>Immunoglobulin heavy-chain genes</dna> contain two <dna>conserved sequence elements</dna> 5 ' to the site of transcription initiation : the octamer ATGCAAAT and the heptamer CTCATGA ."}114{"id": "113", "text": "Both of these elements are required for normal cell-specific promoter function .", "annotated_text": "Both of these elements are required for <dna>normal cell-specific promoter</dna> function ."}115{"id": "114", "text": "The present study demonstrates that both the ubiquitous and lymphoid-cell-specific octamer transcription factors ( OTF-1 and OTF-2 , respectively ) interact specifically with each of the two conserved sequence elements , forming either homo- or heterodimeric complexes .", "annotated_text": "The present study demonstrates that both the <protein>ubiquitous and lymphoid-cell-specific octamer transcription factors</protein> ( <protein>OTF-1</protein> and <protein>OTF-2</protein> , respectively ) interact specifically with each of the two <dna>conserved sequence elements</dna> , forming either <protein>homo- or heterodimeric complexes</protein> ."}116{"id": "115", "text": "This was surprising , since the heptamer and octamer sequence motifs bear no obvious similarity to each other .", "annotated_text": "This was surprising , since the heptamer and octamer sequence motifs bear no obvious similarity to each other ."}117{"id": "116", "text": "Binding of either factor to the octamer element occurred independently .", "annotated_text": "Binding of either factor to the <dna>octamer element</dna> occurred independently ."}118{"id": "117", "text": "However , OTF interaction with the heptamer sequence appeared to require the presence of an intact octamer motif and occurred with a spacing of either 2 or 14 base pairs between the two elements , suggesting coordinate binding resulting from protein-protein interactions .", "annotated_text": "However , <protein>OTF</protein> interaction with the <dna>heptamer sequence</dna> appeared to require the presence of an intact octamer motif and occurred with a spacing of either <dna>2 or 14 base pairs</dna> between the two elements , suggesting coordinate binding resulting from protein-protein interactions ."}119{"id": "118", "text": "The degeneracy in sequences recognized by the OTFs may be important in widening the range over which gene expression can be modulated and in establishing cell type specificity .", "annotated_text": "The degeneracy in sequences recognized by the <protein>OTFs</protein> may be important in widening the range over which gene expression can be modulated and in establishing cell type specificity ."}120{"id": "119", "text": "Identification of a novel lymphoid specific octamer binding protein ( OTF-2B ) by proteolytic clipping bandshift assay ( PCBA ) .", "annotated_text": "Identification of a novel <protein>lymphoid specific octamer binding protein</protein> ( <protein>OTF-2B</protein> ) by proteolytic clipping bandshift assay ( PCBA ) ."}121{"id": "120", "text": "The octamer sequence ATGCAAAT is found in the promoters of immunoglobulin ( Ig ) heavy and light chain genes and in the heavy chain enhancer and is a major determinant of the cell type specific expression of Ig genes in B cells .", "annotated_text": "The octamer sequence ATGCAAAT is found in the promoters of <dna>immunoglobulin ( Ig ) heavy and light chain genes</dna> and in the <dna>heavy chain enhancer</dna> and is a major determinant of the cell type specific expression of <dna>Ig genes</dna> in <cell_type>B cells</cell_type> ."}122{"id": "121", "text": "An apparent paradox is that the same sequence serves as an upstream promoter or enhancer element in a variety of housekeeping genes such as the histone H2B and U snRNA genes .", "annotated_text": "An apparent paradox is that the same sequence serves as an <dna>upstream promoter or enhancer element</dna> in a variety of <dna>housekeeping genes</dna> such as the <dna>histone H2B and U snRNA genes</dna> ."}123{"id": "122", "text": "The differential usage of this regulatory sequence motif is thought to be mediated by different species of octamer binding proteins .", "annotated_text": "The differential usage of this regulatory sequence motif is thought to be mediated by different species of <protein>octamer binding proteins</protein> ."}124{"id": "123", "text": "One species of 100 kd , designated OTF-1 , is present in all cell types and may exert its activating function only when it can interact with additional adjacent transcription factors .", "annotated_text": "One species of 100 kd , designated <protein>OTF-1</protein> , is present in all cell types and may exert its activating function only when it can interact with additional adjacent <protein>transcription factors</protein> ."}125{"id": "124", "text": "The lymphoid cell specific octamer binding protein of 60 kd ( OTF-2A ) specifically stimulates Ig promoters which consist essentially of a TATA-box and an octamer sequence upstream of it .", "annotated_text": "The <protein>lymphoid cell specific octamer binding protein</protein> of 60 kd ( <protein>OTF-2A</protein> ) specifically stimulates <dna>Ig promoters</dna> which consist essentially of a <dna>TATA-box</dna> and an <dna>octamer sequence</dna> upstream of it ."}126{"id": "125", "text": "Here we present evidence for yet another B cell specific octamer binding protein of 75 kd ( OTF-2B ) .", "annotated_text": "Here we present evidence for yet another <protein>B cell specific octamer binding protein</protein> of 75 kd ( <protein>OTF-2B</protein> ) ."}127{"id": "126", "text": "From several findings , including the absence of OTF-2B ( but not OTF-2A ) from a lymphocyte line that can not respond to the IgH enhancer , we propose a role of the novel octamer factor in the long range activation by the IgH enhancer .", "annotated_text": "From several findings , including the absence of <protein>OTF-2B</protein> ( but not <protein>OTF-2A</protein> ) from a <cell_line>lymphocyte line</cell_line> that can not respond to the <dna>IgH enhancer</dna> , we propose a role of the <protein>novel octamer factor</protein> in the long range activation by the <dna>IgH enhancer</dna> ."}128{"id": "127", "text": "We have used the proteolytic clipping bandshift assay ( PCBA ) technique to distinguish the three different forms found in B cells .", "annotated_text": "We have used the proteolytic clipping bandshift assay ( PCBA ) technique to distinguish the three different forms found in <cell_type>B cells</cell_type> ."}129{"id": "128", "text": "This analysis indicates that the 75 kd-species OTF-2B is closely related to the 60 kd species OTF-2A .", "annotated_text": "This analysis indicates that the 75 kd-species <protein>OTF-2B</protein> is closely related to the <protein>60 kd species OTF-2A</protein> ."}130{"id": "129", "text": "Inhibition of interleukin 2 -induced proliferation of cloned murine T cells by glucocorticoids .", "annotated_text": "Inhibition of <protein>interleukin 2</protein> -induced proliferation of <cell_line>cloned murine T cells</cell_line> by glucocorticoids ."}131{"id": "130", "text": "Possible involvement of an inhibitory protein .", "annotated_text": "Possible involvement of an <protein>inhibitory protein</protein> ."}132{"id": "131", "text": "The ability of glucocorticoids to inhibit interleukin 2 ( IL 2 ) -induced T cell proliferation in two cytotoxic T cell ( CTL ) clones has been studied .", "annotated_text": "The ability of glucocorticoids to inhibit <protein>interleukin 2</protein> ( <protein>IL 2</protein> ) -induced <cell_type>T cell</cell_type> proliferation in two <cell_line>cytotoxic T cell ( CTL ) clones</cell_line> has been studied ."}133{"id": "132", "text": "A complete inhibition of DNA synthesis by dexamethasone ( Dx ) could be observed when IL 2-depleted cultures of CTL were either incubated for 6 h with the hormone prior to the addition of IL 2 or treated simultaneously with Dx and a low concentration of IL 2 .", "annotated_text": "A complete inhibition of DNA synthesis by dexamethasone ( Dx ) could be observed when <cell_line>IL 2-depleted cultures</cell_line> of <cell_line>CTL</cell_line> were either incubated for 6 h with the <protein>hormone</protein> prior to the addition of <protein>IL 2</protein> or treated simultaneously with Dx and a low concentration of <protein>IL 2</protein> ."}134{"id": "133", "text": "No significant reduction in the number and affinity of IL 2 receptors was seen after 6 h incubation with Dx .", "annotated_text": "No significant reduction in the number and affinity of <protein>IL 2 receptors</protein> was seen after 6 h incubation with Dx ."}135{"id": "134", "text": "The order of potency observed with the different steroids indicated that this inhibitory effect was mediated through binding to a specific glucocorticoid receptor .", "annotated_text": "The order of potency observed with the different steroids indicated that this inhibitory effect was mediated through binding to a specific <protein>glucocorticoid receptor</protein> ."}136{"id": "135", "text": "The action of these hormones possibly involves the synthesis of an inhibitory protein ( s ) , since the presence of cycloheximide during the incubation with Dx prevented the inhibition of DNA synthesis .", "annotated_text": "The action of these <protein>hormones</protein> possibly involves the synthesis of an <protein>inhibitory protein</protein> ( s ) , since the presence of cycloheximide during the incubation with Dx prevented the inhibition of DNA synthesis ."}137{"id": "136", "text": "Furthermore , supernatant from Dx-treated CTL contained a nondialyzable factor which inhibited DNA synthesis and cell growth of CTL clones induced by IL 2 .", "annotated_text": "Furthermore , supernatant from Dx-treated <cell_line>CTL</cell_line> contained a nondialyzable factor which inhibited DNA synthesis and cell growth of <cell_line>CTL clones</cell_line> induced by <protein>IL 2</protein> ."}138{"id": "137", "text": "Blocking of IL 2 synthesis and IL 2 receptor formation have been proposed as one of the major mechanisms of glucocorticoid-induced immunosuppression .", "annotated_text": "Blocking of <protein>IL 2</protein> synthesis and <protein>IL 2 receptor</protein> formation have been proposed as one of the major mechanisms of glucocorticoid-induced immunosuppression ."}139{"id": "138", "text": "Our results indicate that these hormones may also affect T cell proliferation by inhibiting IL 2 activity .", "annotated_text": "Our results indicate that these <protein>hormones</protein> may also affect <cell_type>T cell</cell_type> proliferation by inhibiting <protein>IL 2</protein> activity ."}140{"id": "139", "text": "Identification and purification of a human immunoglobulin-enhancer-binding protein ( NF-kappa B ) that activates transcription from a human immunodeficiency virus type 1 promoter in vitro .", "annotated_text": "Identification and purification of a <protein>human immunoglobulin-enhancer-binding protein</protein> ( <protein>NF-kappa B</protein> ) that activates transcription from a <dna>human immunodeficiency virus type 1 promoter</dna> in vitro ."}141{"id": "140", "text": "The enhancer-binding factor NF-kappa B , which is found only in cells that transcribe immunoglobulin light chain genes , has been purified from nuclear extracts of Namalwa cells ( human Burkitt lymphoma cells ) by sequence-specific DNA affinity chromatography .", "annotated_text": "The <protein>enhancer-binding factor NF-kappa B</protein> , which is found only in cells that transcribe <dna>immunoglobulin light chain genes</dna> , has been purified from nuclear extracts of <cell_line>Namalwa cells</cell_line> ( <cell_line>human Burkitt lymphoma cells</cell_line> ) by sequence-specific DNA affinity chromatography ."}142{"id": "141", "text": "The purified NF-kappa B has been identified as a 51-kDa polypeptide by UV-crosslinking analysis .", "annotated_text": "The purified <protein>NF-kappa B</protein> has been identified as a <protein>51-kDa polypeptide</protein> by UV-crosslinking analysis ."}143{"id": "142", "text": "`` Footprint '' and methylation-interference analyses have shown that purified NF-kappa B has a binding activity specific for the kappa light chain enhancer sequence .", "annotated_text": "`` Footprint '' and methylation-interference analyses have shown that purified <protein>NF-kappa B</protein> has a binding activity specific for the <dna>kappa light chain enhancer sequence</dna> ."}144{"id": "143", "text": "The purified factor activated in vitro transcription of the human immunodeficiency virus type I promoter by binding to an upstream NF-kappa B-binding site", "annotated_text": "The purified factor activated in vitro transcription of the <dna>human immunodeficiency virus type I promoter</dna> by binding to an <dna>upstream NF-kappa B-binding site</dna>"}145{"id": "144", "text": "Lymphocyte glucocorticoid receptor binding in depression : normal values following recovery .", "annotated_text": "<cell_type>Lymphocyte</cell_type> <protein>glucocorticoid receptor</protein> binding in depression : normal values following recovery ."}146{"id": "145", "text": "The number of glucocorticoid receptor sites in lymphocytes and plasma cortisol concentrations were measured in 20 patients who had recovered from major depressive disorder and 20 healthy control subjects .", "annotated_text": "The number of <protein>glucocorticoid receptor</protein> sites in <cell_type>lymphocytes</cell_type> and plasma cortisol concentrations were measured in 20 patients who had recovered from major depressive disorder and 20 healthy control subjects ."}147{"id": "146", "text": "The number of glucocorticoid receptor sites in lymphocytes from the recovered depressed group was not significantly different from that of the control group .", "annotated_text": "The number of <protein>glucocorticoid receptor</protein> sites in <cell_type>lymphocytes</cell_type> from the recovered depressed group was not significantly different from that of the control group ."}148{"id": "147", "text": "Although the mean plasma cortisol concentration in recovered depressives was higher than in control subjects , the difference only just reached significance .", "annotated_text": "Although the mean plasma cortisol concentration in recovered depressives was higher than in control subjects , the difference only just reached significance ."}149{"id": "148", "text": "This study shows that the reduction in glucocorticoid receptor numbers which occurs during acute depressive illness does not persist on recovery and is , therefore , state-dependent .", "annotated_text": "This study shows that the reduction in <protein>glucocorticoid receptor</protein> numbers which occurs during acute depressive illness does not persist on recovery and is , therefore , state-dependent ."}150{"id": "149", "text": "Identification and purification of a human lymphoid-specific octamer-binding protein ( OTF-2 ) that activates transcription of an immunoglobulin promoter in vitro .", "annotated_text": "Identification and purification of a <protein>human lymphoid-specific octamer-binding protein</protein> ( <protein>OTF-2</protein> ) that activates transcription of an <dna>immunoglobulin promoter</dna> in vitro ."}151{"id": "150", "text": "The octamer sequence 5'-ATGCAAAT , in either orientation , serves as an upstream element in a variety of promoters and also occurs as a modular enhancer element .", "annotated_text": "The octamer sequence 5'-ATGCAAAT , in either orientation , serves as an <dna>upstream element</dna> in a variety of <dna>promoters</dna> and also occurs as a <dna>modular enhancer element</dna> ."}152{"id": "151", "text": "It is of particular interest in immunoglobulin genes since it is found in the upstream regions of all heavy and light chain promoters and in the heavy chain enhancer , both of which are known to be necessary for cell-specific expression .", "annotated_text": "It is of particular interest in <dna>immunoglobulin genes</dna> since it is found in the <dna>upstream regions</dna> of all <dna>heavy and light chain promoters</dna> and in the <dna>heavy chain enhancer</dna> , both of which are known to be necessary for cell-specific expression ."}153{"id": "152", "text": "We report here the chromatographic separation of ubiquitous and B cell-specific octamer-binding proteins .", "annotated_text": "We report here the chromatographic separation of <protein>ubiquitous and B cell-specific octamer-binding proteins</protein> ."}154{"id": "153", "text": "The B cell factor was purified to homogeneity using affinity chromatography and consists of three peptides of 62 , 61 , and 58.5 +/- 1.5 kd .", "annotated_text": "The <protein>B cell factor</protein> was purified to homogeneity using affinity chromatography and consists of three peptides of 62 , 61 , and 58.5 +/- 1.5 kd ."}155{"id": "154", "text": "Each of the polypeptides was renatured after SDS-PAGE and shown to bind to the octamer sequence .", "annotated_text": "Each of the polypeptides was renatured after SDS-PAGE and shown to bind to the octamer sequence ."}156{"id": "155", "text": "The specific DNA binding activity of the pure B cell-specific factor was indistinguishable from that of the affinity-purified ubiquitous factor .", "annotated_text": "The specific DNA binding activity of the pure <protein>B cell-specific factor</protein> was indistinguishable from that of the <protein>affinity-purified ubiquitous factor</protein> ."}157{"id": "156", "text": "This B cell-specific octamer-binding factor , in pure form , activated transcription from a kappa light chain promoter in vitro , thus demonstrating that it is indeed a B cell-specific transcription factor for this gene .", "annotated_text": "This <protein>B cell-specific octamer-binding factor</protein> , in pure form , activated transcription from a <dna>kappa light chain promoter</dna> in vitro , thus demonstrating that it is indeed a <protein>B cell-specific transcription factor</protein> for this gene ."}158{"id": "157", "text": "In addition to the ubiquitous and B cell-specific octamer-binding factors , we identified several additional proteins , one of which is B cell -specific , that interact with the kappa promoter .", "annotated_text": "In addition to the <protein>ubiquitous and B cell-specific octamer-binding factors</protein> , we identified several additional proteins , one of which is <cell_type>B cell</cell_type> -specific , that interact with the <dna>kappa promoter</dna> ."}159{"id": "158", "text": "Decreased deoxyribonucleic acid binding of glucocorticoid-receptor complex in cultured skin fibroblasts from a patient with the glucocorticoid resistance syndrome .", "annotated_text": "Decreased deoxyribonucleic acid binding of <protein>glucocorticoid-receptor complex</protein> in cultured <cell_line>skin fibroblasts</cell_line> from a patient with the glucocorticoid resistance syndrome ."}160{"id": "159", "text": "A patient with the syndrome of glucocorticoid resistance was studied .", "annotated_text": "A patient with the syndrome of glucocorticoid resistance was studied ."}161{"id": "160", "text": "A 27-yr-old woman initially was diagnosed as having Cushing 's disease , based on the findings of high plasma ACTH and serum cortisol levels , increased urinary cortisol secretion , resistance to adrenal suppression with dexamethasone , and bilateral adrenal hyperplasia by computed tomography and scintigraphy of the adrenal glands .", "annotated_text": "A 27-yr-old woman initially was diagnosed as having Cushing 's disease , based on the findings of high plasma ACTH and serum cortisol levels , increased urinary cortisol secretion , resistance to adrenal suppression with dexamethasone , and bilateral adrenal hyperplasia by computed tomography and scintigraphy of the adrenal glands ."}162{"id": "161", "text": "However , she had no signs or symptoms of Cushing 's syndrome .", "annotated_text": "However , she had no signs or symptoms of Cushing 's syndrome ."}163{"id": "162", "text": "During a 5-yr follow-up , no clinical abnormalities developed , although hypercortisolism persisted .", "annotated_text": "During a 5-yr follow-up , no clinical abnormalities developed , although hypercortisolism persisted ."}164{"id": "163", "text": "End-organ resistance to cortisol was suspected .", "annotated_text": "End-organ resistance to cortisol was suspected ."}165{"id": "164", "text": "To explain the end-organ resistance to cortisol , the glucocorticoid receptors ( GR ) in peripheral mononuclear leukocytes and cultured skin fibroblasts from a forearm skin biopsy were characterized and compared with the results of similar studies in normal subjects .", "annotated_text": "To explain the end-organ resistance to cortisol , the <protein>glucocorticoid receptors</protein> ( <protein>GR</protein> ) in <cell_type>peripheral mononuclear leukocytes</cell_type> and <cell_line>cultured skin fibroblasts</cell_line> from a forearm skin biopsy were characterized and compared with the results of similar studies in normal subjects ."}166{"id": "165", "text": "The patient 's GR in whole cell assays had an increased dissociation constant ( Kd ) .", "annotated_text": "The patient 's <protein>GR</protein> in whole cell assays had an increased dissociation constant ( Kd ) ."}167{"id": "166", "text": "In the cytosol of cultured skin fibroblasts from the patient , there was also decreased binding capacity .", "annotated_text": "In the cytosol of <cell_line>cultured skin fibroblasts</cell_line> from the patient , there was also decreased binding capacity ."}168{"id": "167", "text": "The thermal stability and the sedimentation coefficient in a sucrose density gradient of the receptors in the cytosol of cultured skin fibroblasts from the patient and normal subjects were similar .", "annotated_text": "The thermal stability and the sedimentation coefficient in a sucrose density gradient of the receptors in the cytosol of <cell_line>cultured skin fibroblasts</cell_line> from the patient and normal subjects were similar ."}169{"id": "168", "text": "GR complex activation , analyzed by DEAE-cellulose chromatography , was decreased in the patient .", "annotated_text": "<cell_line>GR complex activation</cell_line> , analyzed by <cell_line>DEAE-cellulose chromatography</cell_line> , was decreased in the patient ."}170{"id": "169", "text": "DNA binding of the GR complex after temperature-induced activation was lower in the patient than in normal subjects .", "annotated_text": "<dna>DNA</dna> binding of the <protein>GR complex</protein> after temperature-induced activation was lower in the patient than in normal subjects ."}171{"id": "170", "text": "Nuclear translocation of GR complexes from the patient was also slightly decreased .", "annotated_text": "Nuclear translocation of <protein>GR complexes</protein> from the patient was also slightly decreased ."}172{"id": "171", "text": "These results suggest that the patient 's glucocorticoid resistance was due to a decrease in the affinity of the receptor for glucocorticoids and a decrease in the binding of the GR complex to DNA .", "annotated_text": "These results suggest that the patient 's glucocorticoid resistance was due to a decrease in the affinity of the receptor for glucocorticoids and a decrease in the binding of the <protein>GR complex</protein> to <dna>DNA</dna> ."}173{"id": "172", "text": "Granulocyte-macrophage colony-stimulating factor .", "annotated_text": "<protein>Granulocyte-macrophage colony-stimulating factor</protein> ."}174{"id": "173", "text": "Sensitive and receptor-mediated regulation by 1 , 25-dihydroxyvitamin D3 in normal human peripheral blood lymphocytes .", "annotated_text": "Sensitive and receptor-mediated regulation by 1 , 25-dihydroxyvitamin D3 in normal <cell_type>human peripheral blood lymphocytes</cell_type> ."}175{"id": "174", "text": "We show that 1 , 25-dihydroxyvitamin D3 ( 1 , 25 [ OH ] 2D3 ) , the most hormonally active metabolite of vitamin D3 , modulates sensitively and specifically both the protein and messenger RNA accumulation of the multilineage growth factor granulocyte-macrophage colony-stimulating factor ( GM-CSF ) .", "annotated_text": "We show that 1 , 25-dihydroxyvitamin D3 ( 1 , 25 [ OH ] 2D3 ) , the most hormonally active metabolite of vitamin D3 , modulates sensitively and specifically both the protein and <rna>messenger RNA</rna> accumulation of the <protein>multilineage growth factor</protein> <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) ."}176{"id": "175", "text": "The regulation of GM-CSF expression is seen in both normal human mitogen-activated T lymphocytes and T lymphocytes from a line ( S-LB1 ) transformed with human T cell lymphotropic virus 1 ( HTLV-1 ) .", "annotated_text": "The regulation of <protein>GM-CSF</protein> expression is seen in both <cell_type>normal human mitogen-activated T lymphocytes</cell_type> and <cell_line>T lymphocytes from a line ( S-LB1 ) transformed with human T cell lymphotropic virus 1</cell_line> ( HTLV-1 ) ."}177{"id": "176", "text": "In contrast , cells from a HTLV-1 transformed T lymphocyte line ( Ab-VDR ) established from a patient with vitamin D-resistant rickets type II with undetectable 1 , 25 ( OH ) 2D3 cellular receptors are resistant to the action of 1 , 25 ( OH ) 2D3 .", "annotated_text": "In contrast , cells from a <cell_line>HTLV-1 transformed T lymphocyte line</cell_line> ( <cell_line>Ab-VDR</cell_line> ) established from a patient with vitamin D-resistant rickets type II with undetectable <protein>1 , 25 ( OH ) 2D3 cellular receptors</protein> are resistant to the action of 1 , 25 ( OH ) 2D3 ."}178{"id": "177", "text": "Inhibition of GM-CSF expression by 1 , 25 ( OH ) 2D3 can occur independently of interleukin 2 regulation and is probably mediated through cellular 1 , 25 ( OH ) 2D3 receptors .", "annotated_text": "Inhibition of <protein>GM-CSF</protein> expression by 1 , 25 ( OH ) 2D3 can occur independently of <protein>interleukin 2</protein> regulation and is probably mediated through <protein>cellular 1 , 25 ( OH ) 2D3 receptors</protein> ."}179{"id": "178", "text": "We conclude that 1 , 25 ( OH ) 2D3 may be important in the physiology of hematopoiesis .", "annotated_text": "We conclude that 1 , 25 ( OH ) 2D3 may be important in the physiology of hematopoiesis ."}180{"id": "179", "text": "Altered interaction between triiodothyronine and its nuclear receptors in absence of cortisol : a proposed mechanism for increased thyrotropin secretion in corticosteroid deficiency states .", "annotated_text": "Altered interaction between triiodothyronine and its <protein>nuclear receptors</protein> in absence of cortisol : a proposed mechanism for increased thyrotropin secretion in corticosteroid deficiency states ."}181{"id": "180", "text": "Thyroid hormones occasionally appear less effective when administered alone to patients with panhypopituitarism , and manifestations suggestive of hypothyroidism have been reported in patients suffering from untreated Addison 's disease .", "annotated_text": "Thyroid hormones occasionally appear less effective when administered alone to patients with panhypopituitarism , and manifestations suggestive of hypothyroidism have been reported in patients suffering from untreated Addison 's disease ."}182{"id": "181", "text": "In the latter condition , thyrotropin secretion is increased : this occurs already after as little as 2 days of temporary withdrawal of therapy with substitution doses of corticosteroids while circulating levels of thyroid hormones remain within normal limits .", "annotated_text": "In the latter condition , thyrotropin secretion is increased : this occurs already after as little as 2 days of temporary withdrawal of therapy with substitution doses of corticosteroids while circulating levels of thyroid hormones remain within normal limits ."}183{"id": "182", "text": "Therefore , a possible role of cortisol in interaction between triiodothyronine and its nuclear receptors was examined at the level of circulating lymphocytes obtained from patients with primary or secondary adrenocortical failure .", "annotated_text": "Therefore , a possible role of cortisol in interaction between triiodothyronine and its <protein>nuclear receptors</protein> was examined at the level of circulating lymphocytes obtained from patients with primary or secondary adrenocortical failure ."}184{"id": "183", "text": "The affinity of these receptors was found to be decreased , by more than 50 % on average , in the absence of cortisol treatments .", "annotated_text": "The affinity of these receptors was found to be decreased , by more than 50 % on average , in the absence of cortisol treatments ."}185{"id": "184", "text": "This change was promptly corrected upon resumption of therapy .", "annotated_text": "This change was promptly corrected upon resumption of therapy ."}186{"id": "185", "text": "The number of binding sites was not significantly modified .", "annotated_text": "The number of binding sites was not significantly modified ."}187{"id": "186", "text": "The influence of cortisol on thyroid hormone receptors discussed here might account for the clinical observations mentioned above .", "annotated_text": "The influence of cortisol on <protein>thyroid hormone receptors</protein> discussed here might account for the clinical observations mentioned above ."}188{"id": "187", "text": "Inhibition by cortisol of human natural killer ( NK ) cell activity .", "annotated_text": "Inhibition by cortisol of <cell_type>human natural killer ( NK ) cell</cell_type> activity ."}189{"id": "188", "text": "The effects of cortisol on the natural killer ( NK ) activity of human peripheral blood mononuclear ( PBM ) cells were studied in vitro using a direct 4-h 51Cr-release assay and K 562 cell line as a target .", "annotated_text": "The effects of cortisol on the <cell_type>natural killer</cell_type> ( NK ) activity of <cell_type>human peripheral blood mononuclear ( PBM ) cells</cell_type> were studied in vitro using a direct 4-h 51Cr-release assay and <cell_line>K 562 cell line</cell_line> as a target ."}190{"id": "189", "text": "Preincubation for 20 h of PBM cells drawn from healthy donors with 1 X 10 ( -8 ) to 1 X 10 ( -5 ) M cortisol resulted in a significant decrease of NK cell activity .", "annotated_text": "Preincubation for 20 h of <cell_type>PBM cells</cell_type> drawn from healthy donors with 1 X 10 ( -8 ) to 1 X 10 ( -5 ) M cortisol resulted in a significant decrease of <cell_type>NK cell</cell_type> activity ."}191{"id": "190", "text": "The magnitude of the suppression was directly related to the steroid concentration and inversely related to the number of effector cells .", "annotated_text": "The magnitude of the suppression was directly related to the steroid concentration and inversely related to the number of <cell_type>effector cells</cell_type> ."}192{"id": "191", "text": "Cortisol was able to minimize the enhancement of NK cytotoxicity obtainable in the presence of immune interferon ( IFN-gamma ) .", "annotated_text": "Cortisol was able to minimize the enhancement of NK cytotoxicity obtainable in the presence of immune interferon ( IFN-gamma ) ."}193{"id": "192", "text": "A significantly higher suppression was achieved after sequential exposure of PBM cells to cortisol and equimolar levels of prostaglandin E2 ( PgE2 ) .", "annotated_text": "A significantly higher suppression was achieved after sequential exposure of <cell_type>PBM cells</cell_type> to cortisol and equimolar levels of prostaglandin E2 ( PgE2 ) ."}194{"id": "193", "text": "The concomitant incubation with theophylline and isobutyl-methylxanthine failed to enhance the cortisol-induced suppression , whereas PgE2-dependent inhibition significantly increased after exposure of PBM cells to methyl-xanthines .", "annotated_text": "The concomitant incubation with theophylline and isobutyl-methylxanthine failed to enhance the cortisol-induced suppression , whereas PgE2-dependent inhibition significantly increased after exposure of <cell_type>PBM cells</cell_type> to methyl-xanthines ."}195{"id": "194", "text": "The inhibitory effect of cortisol was partially or totally prevented by the concomitant incubation with equimolar amounts of 11-deoxycortisol and RU 486 but not of progesterone .", "annotated_text": "The inhibitory effect of cortisol was partially or totally prevented by the concomitant incubation with equimolar amounts of 11-deoxycortisol and RU 486 but not of progesterone ."}196{"id": "195", "text": "Treatment of NK effectors with a monoclonal anti-human corticosteroid-binding globulin ( CBG ) antibody produced an enhancement of the spontaneous NK activity and a partial suppression of cortisol-mediated effects .", "annotated_text": "Treatment of <cell_type>NK effectors</cell_type> with a <protein>monoclonal anti-human corticosteroid-binding globulin ( CBG ) antibody</protein> produced an enhancement of the spontaneous <cell_type>NK</cell_type> activity and a partial suppression of cortisol-mediated effects ."}197{"id": "196", "text": "Our results suggest that endogenous glucocorticoids play a role in the regulation of NK cell-mediated cytotoxicity .", "annotated_text": "Our results suggest that endogenous glucocorticoids play a role in the regulation of NK cell-mediated cytotoxicity ."}198{"id": "197", "text": "Since the effect of cortisol was additive to that of PgE2 and was not changed by phosphodiesterase inhibitors , it is conceivable that the hormone acts at a level different from the adenylate cyclase - phosphodiesterase system .", "annotated_text": "Since the effect of cortisol was additive to that of PgE2 and was not changed by <protein>phosphodiesterase</protein> inhibitors , it is conceivable that the hormone acts at a level different from the <protein>adenylate cyclase</protein> - <protein>phosphodiesterase</protein> system ."}199{"id": "198", "text": "Data obtained with the use of antiglucocorticoids and the anti-CBG antibody are compatible with a role both of high-affinity glucocorticoid receptors and of CBG in mediating cortisol action on the human NK cell activity .", "annotated_text": "Data obtained with the use of antiglucocorticoids and the <protein>anti-CBG antibody</protein> are compatible with a role both of high-affinity <protein>glucocorticoid receptors</protein> and of <protein>CBG</protein> in mediating cortisol action on the <cell_type>human NK cell</cell_type> activity ."}200{"id": "199", "text": "Interaction of cell-type-specific nuclear proteins with immunoglobulin VH promoter region sequences .", "annotated_text": "Interaction of <protein>cell-type-specific nuclear proteins</protein> with <dna>immunoglobulin VH promoter region sequences</dna> ."}201{"id": "200", "text": "All human and murine immunoglobulin heavy chain variable region ( VH ) genes contain the sequence ATGCAAAT approximately 70 nucleotides 5 ' from the site of transcription initiation .", "annotated_text": "All <dna>human and murine immunoglobulin heavy chain variable region ( VH ) genes</dna> contain the sequence ATGCAAAT approximately 70 nucleotides 5 ' from the site of transcription initiation ."}202{"id": "201", "text": "This octanucleotide , in reverse orientation , is also found in all light chain variable region ( VL ) genes , and in the immunoglobulin heavy chain transcriptional enhancer .", "annotated_text": "This octanucleotide , in reverse orientation , is also found in all <dna>light chain variable region ( VL ) genes</dna> , and in the <dna>immunoglobulin heavy chain transcriptional enhancer</dna> ."}203{"id": "202", "text": "Transfection studies have established that this octamer is involved in the lymphoid-specific transcription of immunoglobulin genes .", "annotated_text": "Transfection studies have established that this octamer is involved in the lymphoid-specific transcription of <dna>immunoglobulin genes</dna> ."}204{"id": "203", "text": "Octamer-containing fragments have been reported to bind a factor present in nuclear extracts of human cell lines ; however , identical binding activity was detected in both B lymphoid and non-lymphoid cells .", "annotated_text": "<dna>Octamer-containing fragments</dna> have been reported to bind a factor present in nuclear extracts of <cell_line>human cell lines</cell_line> ; however , identical binding activity was detected in both <cell_line>B lymphoid and non-lymphoid cells</cell_line> ."}205{"id": "204", "text": "Here we establish that nuclear extracts from distinct cell types differ in their ability to interact with octamer-containing fragments .", "annotated_text": "Here we establish that nuclear extracts from distinct cell types differ in their ability to interact with <dna>octamer-containing fragments</dna> ."}206{"id": "205", "text": "We have also detected a DNA-protein interaction that may be involved in the cell-type specificity of immunoglobulin expression , and we have determined that a sequence upstream of the octamer participates in an interaction with a nuclear protein ( s ) .", "annotated_text": "We have also detected a DNA-protein interaction that may be involved in the cell-type specificity of <protein>immunoglobulin</protein> expression , and we have determined that a sequence upstream of the octamer participates in an interaction with a <protein>nuclear protein</protein> ( s ) ."}207{"id": "206", "text": "Preferential transcription of HTLV-I LTR in cell-free extracts of human T cells producing HTLV-I viral proteins .", "annotated_text": "Preferential transcription of <dna>HTLV-I LTR</dna> in cell-free extracts of <cell_type>human T cells</cell_type> producing <protein>HTLV-I viral proteins</protein> ."}208{"id": "207", "text": "The promoters of the adenovirus 2 major late gene , the mouse beta-globin gene , the mouse immunoglobulin VH gene and the LTR of the human T-lymphotropic retrovirus type I were tested for their transcription activities in cell-free extracts of four cell lines ; HeLa , CESS ( Epstein-Barr virus-transformed human B cell line ) , MT-1 ( HTLV-I-infected human T cell line without viral protein synthesis ) , and MT-2 ( HTLV-I-infected human T cell line producing viral proteins ) .", "annotated_text": "The <dna>promoters</dna> of the <dna>adenovirus 2 major late gene</dna> , the <dna>mouse beta-globin gene</dna> , the <dna>mouse immunoglobulin VH gene</dna> and the <dna>LTR</dna> of the human T-lymphotropic retrovirus type I were tested for their transcription activities in cell-free extracts of four cell lines ; <cell_line>HeLa</cell_line> , <cell_line>CESS</cell_line> ( <cell_line>Epstein-Barr virus-transformed human B cell line</cell_line> ) , <cell_line>MT-1</cell_line> ( <cell_line>HTLV-I-infected human T cell line</cell_line> without viral protein synthesis ) , and <cell_line>MT-2</cell_line> ( <cell_line>HTLV-I-infected human T cell line</cell_line> producing <protein>viral proteins</protein> ) ."}209{"id": "208", "text": "LTR was preferentially transcribed in the extracts of MT-2 although the other three genes were transcribed with relatively constant efficiencies in different extracts .", "annotated_text": "<dna>LTR</dna> was preferentially transcribed in the extracts of <cell_line>MT-2</cell_line> although the other three genes were transcribed with relatively constant efficiencies in different extracts ."}210{"id": "209", "text": "The results agree well with the previous in vivo studies on the promoter activity of HTLV-I LTR .", "annotated_text": "The results agree well with the previous in vivo studies on the promoter activity of <dna>HTLV-I LTR</dna> ."}211{"id": "210", "text": "Mixing of HeLa and MT-2 extracts revealed the presence of a LTR-specific stimulating activity in MT-2 extracts .", "annotated_text": "Mixing of HeLa and MT-2 extracts revealed the presence of a LTR-specific stimulating activity in MT-2 extracts ."}212{"id": "211", "text": "A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes .", "annotated_text": "A <protein>nuclear factor</protein> that binds to a conserved sequence motif in <dna>transcriptional control elements</dna> of <dna>immunoglobulin genes</dna> ."}213{"id": "212", "text": "Trans-acting factors that mediate B-cell specific transcription of immunoglobulin genes have been postulated based on an analysis of the expression of exogenously introduced immunoglobulin gene recombinants in lymphoid and non-lymphoid cells .", "annotated_text": "<protein>Trans-acting factors</protein> that mediate B-cell specific transcription of <dna>immunoglobulin genes</dna> have been postulated based on an analysis of the expression of exogenously introduced <dna>immunoglobulin gene recombinants</dna> in <cell_type>lymphoid and non-lymphoid cells</cell_type> ."}214{"id": "213", "text": "Two B-cell-specific , cis-acting transcriptional regulatory elements have been identified .", "annotated_text": "Two B-cell-specific , <dna>cis-acting transcriptional regulatory elements</dna> have been identified ."}215{"id": "214", "text": "One element is located in the intron between the variable ( V ) and constant ( C ) regions of both heavy and kappa light-chain genes and acts as a transcriptional enhancer .", "annotated_text": "One element is located in the intron between the variable ( V ) and constant ( C ) regions of both <dna>heavy and kappa light-chain genes</dna> and acts as a transcriptional enhancer ."}216{"id": "215", "text": "The second element is found upstream of both heavy and kappa light-chain gene promoters .", "annotated_text": "The second <dna>element</dna> is found upstream of both <dna>heavy and kappa light-chain gene promoters</dna> ."}217{"id": "216", "text": "This element directs lymphoid-specific transcription even in the presence of viral enhancers .", "annotated_text": "This element directs lymphoid-specific transcription even in the presence of <dna>viral enhancers</dna> ."}218{"id": "217", "text": "We have sought nuclear factors that might bind specifically to these two regulatory elements by application of a modified gel electrophoresis DNA binding assay .", "annotated_text": "We have sought nuclear factors that might bind specifically to these two <dna>regulatory elements</dna> by application of a modified gel electrophoresis DNA binding assay ."}219{"id": "218", "text": "We report here the identification of a human B-cell nuclear factor ( IgNF-A ) that binds to DNA sequences in the upstream regions of both the mouse heavy and kappa light-chain gene promoters and also to the mouse heavy-chain gene enhancer .", "annotated_text": "We report here the identification of a <protein>human B-cell nuclear factor</protein> ( <protein>IgNF-A</protein> ) that binds to <dna>DNA sequences</dna> in the <dna>upstream regions</dna> of both the <dna>mouse heavy and kappa light-chain gene promoters</dna> and also to the <dna>mouse heavy-chain gene enhancer</dna> ."}220{"id": "219", "text": "This sequence-specific binding is probably mediated by a highly conserved sequence motif , ATTTGCAT , present in all three transcriptional elements .", "annotated_text": "This sequence-specific binding is probably mediated by a highly conserved sequence motif , ATTTGCAT , present in all three <dna>transcriptional elements</dna> ."}221{"id": "220", "text": "Interestingly , a factor showing similar binding specificity to IgNF-A is also present in human HeLa cells .", "annotated_text": "Interestingly , a factor showing similar binding specificity to <dna>IgNF-A</dna> is also present in <cell_line>human HeLa cells</cell_line> ."}222{"id": "221", "text": "The new world primates as animal models of glucocorticoid resistance .", "annotated_text": "The new world primates as animal models of glucocorticoid resistance ."}223{"id": "222", "text": "Many New World primate species have greatly increased plasma cortisol concentrations , decreased plasma cortisol binding globulin capacity and affinity , marked resistance of the hypothalamic-pituitary-adrenal axis to suppression by dexamethasone , and no biological evidence of glucocorticoid excess .", "annotated_text": "Many New World primate species have greatly increased plasma cortisol concentrations , decreased plasma cortisol binding globulin capacity and affinity , marked resistance of the hypothalamic-pituitary-adrenal axis to suppression by dexamethasone , and no biological evidence of glucocorticoid excess ."}224{"id": "223", "text": "These primates also have high levels of circulating progesterone , estrogen , mineralocorticoid , androgen and vitamin D .", "annotated_text": "These primates also have high levels of circulating progesterone , estrogen , mineralocorticoid , androgen and vitamin D ."}225{"id": "224", "text": "The glucocorticoid target tissues that have been examined ( circulating mononuclear lymphocytes and cultured skin fibroblasts ) have normal concentrations of glucocorticoid receptors with decreased affinity for dexamethasone .", "annotated_text": "The glucocorticoid target tissues that have been examined ( <cell_type>circulating mononuclear lymphocytes</cell_type> and <cell_line>cultured skin fibroblasts</cell_line> ) have normal concentrations of <protein>glucocorticoid receptors</protein> with decreased affinity for dexamethasone ."}226{"id": "225", "text": "Transformation of B-lymphocytes with the Epstein-Barr virus leads to glucocorticoid receptor induction that is less than that observed with cells from Old World primates .", "annotated_text": "Transformation of <cell_type>B-lymphocytes</cell_type> with the Epstein-Barr virus leads to <protein>glucocorticoid receptor</protein> induction that is less than that observed with cells from Old World primates ."}227{"id": "226", "text": "The receptor in these cells has a low affinity for dexamethasone .", "annotated_text": "The receptor in these cells has a low affinity for dexamethasone ."}228{"id": "227", "text": "The low affinity leads to an increased loss of specific bound ligand during thermal activation .", "annotated_text": "The low affinity leads to an increased loss of specific bound ligand during thermal activation ."}229{"id": "228", "text": "Meroreceptor generation is normal .", "annotated_text": "Meroreceptor generation is normal ."}230{"id": "229", "text": "The molecular weight of the receptor , determined by SDS-PAGE , is similar to that of Old World primates ( approximately 92 , 000 ) and the activation pattern per se , examined in vitro by heating cytosol and performing phosphocellulose chromatography , appears similar to that of human controls .", "annotated_text": "The molecular weight of the receptor , determined by SDS-PAGE , is similar to that of Old World primates ( approximately 92 , 000 ) and the activation pattern per se , examined in vitro by heating cytosol and performing phosphocellulose chromatography , appears similar to that of human controls ."}231{"id": "230", "text": "The ratios of nuclear to cytosolic hormone-receptor-complexes and of cytosolic activated to unactivated receptor complexes in intact cells are similar to Old World primates .", "annotated_text": "The ratios of nuclear to <protein>cytosolic hormone-receptor-complexes</protein> and of cytosolic activated to <protein>unactivated receptor complexes</protein> in intact cells are similar to Old World primates ."}232{"id": "231", "text": "Results from mixing studies do not support the hypothesis that a binding inhibitor ( s ) or a deficient cytosolic positive modifier ( s ) of binding underlies the findings in these primates .", "annotated_text": "Results from mixing studies do not support the hypothesis that a binding inhibitor ( s ) or a deficient cytosolic positive modifier ( s ) of binding underlies the findings in these primates ."}233{"id": "232", "text": "The New World primates , unlike men with the syndrome of primary cortisol resistance , have compensated for their condition with intra-adrenal and mineralocorticoid receptor adaptations .", "annotated_text": "The New World primates , unlike men with the syndrome of primary cortisol resistance , have compensated for their condition with intra-adrenal and mineralocorticoid receptor adaptations ."}234{"id": "233", "text": "Thus , unlike Old World primates , cortisol in New World primates has only weak sodium-retaining potency because the aldosterone receptor has a low affinity for cortisol .", "annotated_text": "Thus , unlike Old World primates , cortisol in New World primates has only weak sodium-retaining potency because the <protein>aldosterone receptor</protein> has a low affinity for cortisol ."}235{"id": "234", "text": "The common element that would explain the apparent resistance to six steroid hormones in New World primates", "annotated_text": "The common element that would explain the apparent resistance to six steroid hormones in New World primates"}236{"id": "235", "text": "Acetylation and modulation of erythroid Kruppel-like factor ( EKLF ) activity by interaction with histone acetyltransferases .", "annotated_text": "Acetylation and modulation of <protein>erythroid Kruppel-like factor</protein> ( <protein>EKLF</protein> ) activity by interaction with <protein>histone acetyltransferases</protein> ."}237{"id": "236", "text": "Erythroid Kruppel-like factor ( EKLF ) is a red cell-specific transcriptional activator that is crucial for consolidating the switch to high levels of adult beta-globin expression during erythroid ontogeny .", "annotated_text": "<protein>Erythroid Kruppel-like factor</protein> ( <protein>EKLF</protein> ) is a <protein>red cell-specific transcriptional activator</protein> that is crucial for consolidating the switch to high levels of adult beta-globin expression during erythroid ontogeny ."}238{"id": "237", "text": "EKLF is required for integrity of the chromatin structure at the beta-like globin locus , and it interacts with a positive-acting factor in vivo .", "annotated_text": "<protein>EKLF</protein> is required for integrity of the chromatin structure at the <dna>beta-like globin locus</dna> , and it interacts with a <protein>positive-acting factor</protein> in vivo ."}239{"id": "238", "text": "We find that EKLF is an acetylated transcription factor , and that it interacts in vivo with CBP , p300 , and P/CAF .", "annotated_text": "We find that <protein>EKLF</protein> is an <protein>acetylated transcription factor</protein> , and that it interacts in vivo with <protein>CBP</protein> , <protein>p300</protein> , and <protein>P/CAF</protein> ."}240{"id": "239", "text": "However , its interactions with these histone acetyltransferases are not equivalent , as CBP and p300 , but not P/CAF , utilize EKLF as a substrate for in vitro acetylation within its trans-activation region .", "annotated_text": "However , its interactions with these <protein>histone acetyltransferases</protein> are not equivalent , as <protein>CBP</protein> and <protein>p300</protein> , but not <protein>P/CAF</protein> , utilize <protein>EKLF</protein> as a substrate for in vitro acetylation within its trans-activation region ."}241{"id": "240", "text": "The functional effects of these interactions are that CBP and p300 , but not P/CAF , enhance EKLF 's transcriptional activation of the beta-globin promoter in erythroid cells .", "annotated_text": "The functional effects of these interactions are that <protein>CBP</protein> and <protein>p300</protein> , but not <protein>P/CAF</protein> , enhance <protein>EKLF</protein> 's transcriptional activation of the <dna>beta-globin promoter</dna> in <cell_type>erythroid cells</cell_type> ."}242{"id": "241", "text": "These results establish EKLF as a tissue-specific transcription factor that undergoes post-translational acetylation and suggest a mechanism by which EKLF is able to alter chromatin structure and induce beta-globin expression within the beta-like globin cluster .", "annotated_text": "These results establish <protein>EKLF</protein> as a <protein>tissue-specific transcription factor</protein> that undergoes post-translational acetylation and suggest a mechanism by which <protein>EKLF</protein> is able to alter chromatin structure and induce beta-globin expression within the <dna>beta-like globin cluster</dna> ."}243{"id": "242", "text": "Recognition of herpes simplex virus type 2 tegument proteins by CD4 T cells infiltrating human genital herpes lesions .", "annotated_text": "Recognition of <protein>herpes simplex virus type 2 tegument proteins</protein> by <cell_type>CD4 T cells</cell_type> infiltrating human genital herpes lesions ."}244{"id": "243", "text": "The local cellular immune response to herpes simplex virus ( HSV ) is important in the control of recurrent HSV infection .", "annotated_text": "The local cellular immune response to herpes simplex virus ( HSV ) is important in the control of recurrent HSV infection ."}245{"id": "244", "text": "The antiviral functions of infiltrating CD4-bearing T cells may include cytotoxicity , inhibition of viral growth , lymphokine secretion , and support of humoral and CD8 responses .", "annotated_text": "The antiviral functions of <cell_type>infiltrating CD4-bearing T cells</cell_type> may include cytotoxicity , inhibition of viral growth , lymphokine secretion , and support of humoral and CD8 responses ."}246{"id": "245", "text": "The antigens recognized by many HSV-specific CD4 T cells localizing to genital HSV-2 lesions are unknown .", "annotated_text": "The antigens recognized by many <cell_type>HSV-specific CD4 T cells</cell_type> localizing to genital HSV-2 lesions are unknown ."}247{"id": "246", "text": "T cells recognizing antigens encoded within map units 0.67 to 0.73 of HSV DNA are frequently recovered from herpetic lesions .", "annotated_text": "<cell_type>T cells</cell_type> recognizing antigens encoded within map units 0.67 to 0.73 of <dna>HSV DNA</dna> are frequently recovered from herpetic lesions ."}248{"id": "247", "text": "Expression cloning with this region of DNA now shows that tegument protein VP22 and the viral dUTPase , encoded by genes UL49 and UL50 , respectively , are T-cell antigens .", "annotated_text": "Expression cloning with this region of DNA now shows that <protein>tegument protein</protein> <protein>VP22</protein> and the <protein>viral dUTPase</protein> , encoded by <dna>genes UL49 and UL50</dna> , respectively , are <protein>T-cell antigens</protein> ."}249{"id": "248", "text": "Separate epitopes in VP22 were defined for T-cell clones from each of three patients .", "annotated_text": "Separate <protein>epitopes</protein> in <protein>VP22</protein> were defined for <cell_line>T-cell clones</cell_line> from each of three patients ."}250{"id": "249", "text": "Reactivity with the tegument protein encoded by UL21 was identified for an additional patient .", "annotated_text": "Reactivity with the <protein>tegument protein</protein> encoded by <dna>UL21</dna> was identified for an additional patient ."}251{"id": "250", "text": "Three new epitopes were identified in VP16 , a tegument protein associated with VP22 .", "annotated_text": "Three new epitopes were identified in <protein>VP16</protein> , a <protein>tegument protein</protein> associated with <protein>VP22</protein> ."}252{"id": "251", "text": "Some tegument-specific CD4 T-cell clones exhibited cytotoxic activity against HSV-infected cells .", "annotated_text": "Some <cell_line>tegument-specific CD4 T-cell clones</cell_line> exhibited cytotoxic activity against <cell_type>HSV-infected cells</cell_type> ."}253{"id": "252", "text": "These results suggest that herpes simplex tegument proteins are processed for antigen presentation in vivo and are possible candidate compounds for herpes simplex vaccines .", "annotated_text": "These results suggest that <protein>herpes simplex tegument proteins</protein> are processed for antigen presentation in vivo and are possible candidate compounds for herpes simplex vaccines ."}254{"id": "253", "text": "Fibrinogen activates NF-kappa B transcription factors in mononuclear phagocytes .", "annotated_text": "<protein>Fibrinogen</protein> activates <protein>NF-kappa B transcription factors</protein> in <cell_type>mononuclear phagocytes</cell_type> ."}255{"id": "254", "text": "Adhesion to extracellular matrices is known to modulate leukocyte activation , although the mechanisms are not fully understood .", "annotated_text": "Adhesion to extracellular matrices is known to modulate leukocyte activation , although the mechanisms are not fully understood ."}256{"id": "255", "text": "Mononuclear phagocytes are exposed to fibrinous provisional matrix throughout migration into inflammatory foci , so this study was undertaken to determine whether fibrinogen triggers activation of NF-kappa B transcription factors .", "annotated_text": "<cell_type>Mononuclear phagocytes</cell_type> are exposed to fibrinous provisional matrix throughout migration into inflammatory foci , so this study was undertaken to determine whether fibrinogen triggers activation of <protein>NF-kappa B transcription factors</protein> ."}257{"id": "256", "text": "U937 cells differentiated with PMA in nonadherent culture were shown to express two fibrinogen-binding integrins , predominately CD11b/CD18 , and to a lesser extent , CD11c/CD18 .", "annotated_text": "<cell_line>U937 cells</cell_line> differentiated with PMA in <cell_line>nonadherent culture</cell_line> were shown to express two <protein>fibrinogen-binding integrins</protein> , predominately <protein>CD11b/CD18</protein> , and to a lesser extent , <protein>CD11c/CD18</protein> ."}258{"id": "257", "text": "Cells stimulated with fibrinogen ( 10-100 microg/ml ) /Mn2+ ( 50 microM ) for 2 h were examined by electrophoretic mobility shift assay .", "annotated_text": "Cells stimulated with <protein>fibrinogen</protein> ( 10-100 microg/ml ) /Mn2+ ( 50 microM ) for 2 h were examined by electrophoretic mobility shift assay ."}259{"id": "258", "text": "NF-kappa B activation , minimal in unstimulated cells , was substantially up-regulated by fibrinogen .", "annotated_text": "<protein>NF-kappa B</protein> activation , minimal in <cell_type>unstimulated cells</cell_type> , was substantially up-regulated by <protein>fibrinogen</protein> ."}260{"id": "259", "text": "Fibrinogen also caused activation of AP-1 , but not SP1 or cAMP response element-binding protein ( CREB ) factors .", "annotated_text": "<protein>Fibrinogen</protein> also caused activation of <protein>AP-1</protein> , but not <protein>SP1</protein> or <protein>cAMP response element-binding protein ( CREB ) factors</protein> ."}261{"id": "260", "text": "Blocking mAbs against CD18 and CD11b abrogated fibrinogen -induced NF-kappa B activation .", "annotated_text": "Blocking <protein>mAbs</protein> against <protein>CD18</protein> and <protein>CD11b</protein> abrogated <protein>fibrinogen</protein> -induced <protein>NF-kappa B</protein> activation ."}262{"id": "261", "text": "To determine the effects on transcriptional regulation , U937 cells were transfected with a plasmid containing the HIV-1 enhancer ( bearing two NF-kappa B sites ) coupled to a chloramphenicol acetyltransferase ( CAT ) reporter .", "annotated_text": "To determine the effects on transcriptional regulation , <cell_line>U937 cells</cell_line> were transfected with a plasmid containing the <dna>HIV-1 enhancer</dna> ( bearing two <dna>NF-kappa B sites</dna> ) coupled to a <dna>chloramphenicol acetyltransferase ( CAT ) reporter</dna> ."}263{"id": "262", "text": "Cells were subsequently stimulated with 1 ) PMA for 24 h , inducing CAT activity by 2.6-fold , 2 ) fibrinogen /Mn2+ for 2 h , inducing CAT activity by 3.2-fold , or 3 ) costimulation with fibrinogen and PMA , inducing 5.7-fold the CAT activity induced by PMA alone .", "annotated_text": "Cells were subsequently stimulated with 1 ) PMA for 24 h , inducing CAT activity by 2.6-fold , 2 ) <protein>fibrinogen</protein> /Mn2+ for 2 h , inducing CAT activity by 3.2-fold , or 3 ) costimulation with <protein>fibrinogen</protein> and PMA , inducing 5.7-fold the CAT activity induced by PMA alone ."}264{"id": "263", "text": "We conclude that contact with fibrinogen-derived proteins may contribute to mononuclear phagocyte activation by signaling through CD11b/CD18 , resulting in selective activation of transcriptional regulatory factors , including NF-kappa B .", "annotated_text": "We conclude that contact with <protein>fibrinogen-derived proteins</protein> may contribute to mononuclear phagocyte activation by signaling through <protein>CD11b/CD18</protein> , resulting in selective activation of <protein>transcriptional regulatory factors</protein> , including <protein>NF-kappa B</protein> ."}265{"id": "264", "text": "Peripheral blood T cells and monocytes and B cell lines derived from patients with lupus express estrogen receptor transcripts similar to those of normal cells .", "annotated_text": "<cell_type>Peripheral blood T cells and monocytes</cell_type> and <cell_line>B cell lines</cell_line> derived from patients with lupus express estrogen receptor transcripts similar to those of <cell_type>normal cells</cell_type> ."}266{"id": "265", "text": "OBJECTIVE : To identify and characterize estrogen receptor ( ER ) transcripts expressed in immune cells of patients with systemic lupus erythematosus ( SLE ) and healthy donors .", "annotated_text": "OBJECTIVE : To identify and characterize <rna>estrogen receptor ( ER ) transcripts</rna> expressed in <cell_type>immune cells</cell_type> of patients with systemic lupus erythematosus ( SLE ) and healthy donors ."}267{"id": "266", "text": "METHODS : Peripheral blood monocytes and T cells were prepared from patients with SLE ( n = 6 ) and healthy donors ( n = 8 ) .", "annotated_text": "METHODS : <cell_type>Peripheral blood monocytes and T cells</cell_type> were prepared from patients with SLE ( n = 6 ) and healthy donors ( n = 8 ) ."}268{"id": "267", "text": "T cells were separated into CD4 and CD8 .", "annotated_text": "<cell_type>T cells</cell_type> were separated into <cell_type>CD4</cell_type> and <cell_type>CD8</cell_type> ."}269{"id": "268", "text": "Some monocytes and T cells were stimulated with estradiol , PMA , and ionomycin .", "annotated_text": "Some <cell_type>monocytes</cell_type> and <cell_type>T cells</cell_type> were stimulated with estradiol , PMA , and ionomycin ."}270{"id": "269", "text": "Epstein-Barr virus-transformed B cell lines ( n = 7 ) and B cell hybridomas ( n = 2 ) established from patients with SLE and a healthy individual were used as a B cell source .", "annotated_text": "Epstein-Barr virus-transformed <cell_line>B cell lines</cell_line> ( n = 7 ) and <cell_line>B cell hybridomas</cell_line> ( n = 2 ) established from patients with SLE and a healthy individual were used as a B cell source ."}271{"id": "270", "text": "These cells were examined for ER mRNA by reverse transcription nested polymerase chain reaction .", "annotated_text": "These cells were examined for <rna>ER mRNA</rna> by reverse transcription nested polymerase chain reaction ."}272{"id": "271", "text": "Amplified cDNA were sequenced by standard methods .", "annotated_text": "Amplified <dna>cDNA</dna> were sequenced by standard methods ."}273{"id": "272", "text": "RESULTS : In all cells tested , ER mRNA was expressed without prior in vitro stimulation .", "annotated_text": "RESULTS : In all cells tested , <rna>ER mRNA</rna> was expressed without prior in vitro stimulation ."}274{"id": "273", "text": "Partial sequences from exons 1-8 were nearly identical to the published sequence of the human ER mRNA .", "annotated_text": "Partial sequences from <dna>exons 1-8</dna> were nearly identical to the published sequence of the <rna>human ER mRNA</rna> ."}275{"id": "274", "text": "There were no notable differences in the ER transcripts between patients and healthy controls .", "annotated_text": "There were no notable differences in the <rna>ER transcripts</rna> between patients and healthy controls ."}276{"id": "275", "text": "Variant receptor transcripts lacking exon 5 or exon 7 , which encodes the hormone binding domain , were identified in the majority of the cells .", "annotated_text": "Variant receptor transcripts lacking <dna>exon 5</dna> or <dna>exon 7</dna> , which encodes the <protein>hormone binding domain</protein> , were identified in the majority of the cells ."}277{"id": "276", "text": "Precise deletion of the exons suggests that they are alternatively spliced transcripts .", "annotated_text": "Precise deletion of the exons suggests that they are alternatively spliced transcripts ."}278{"id": "277", "text": "Whether the detected transcripts are translated into functional receptor proteins remains to be determined .", "annotated_text": "Whether the detected transcripts are translated into <protein>functional receptor proteins</protein> remains to be determined ."}279{"id": "278", "text": "In vitro stimulation did not affect ER mRNA expression .", "annotated_text": "In vitro stimulation did not affect <rna>ER mRNA</rna> expression ."}280{"id": "279", "text": "The presence of variants did not correlate with disease activity or medication .", "annotated_text": "The presence of variants did not correlate with disease activity or medication ."}281{"id": "280", "text": "CONCLUSION : Monocytes , T cells , and B cells in patients express transcripts of the normal wild type ER and the hormone binding domain variants in vivo .", "annotated_text": "CONCLUSION : <cell_type>Monocytes</cell_type> , <cell_type>T cells</cell_type> , and <cell_type>B cells</cell_type> in patients express transcripts of the normal <protein>wild type ER</protein> and the <protein>hormone binding domain variants</protein> in vivo ."}282{"id": "281", "text": "DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T lymphocytes via the activation of NF-kappa B and AP-1 .", "annotated_text": "DNA damaging agents induce expression of <protein>Fas ligand</protein> and subsequent apoptosis in <cell_type>T lymphocytes</cell_type> via the activation of <protein>NF-kappa B</protein> and <protein>AP-1</protein> ."}283{"id": "282", "text": "Apoptosis induced by DNA damage and other stresses can proceed via expression of Fas ligand ( FasL ) and ligation of its receptor , Fas ( CD95 ) .", "annotated_text": "Apoptosis induced by DNA damage and other stresses can proceed via expression of <protein>Fas ligand</protein> ( <protein>FasL</protein> ) and ligation of its receptor , Fas ( CD95 ) ."}284{"id": "283", "text": "We report that activation of the two transcription factors NF-kappa B and AP-1 is crucially involved in FasL expression induced by etoposide , teniposide , and UV irradiation .", "annotated_text": "We report that activation of the two <protein>transcription factors NF-kappa B and AP-1</protein> is crucially involved in <protein>FasL</protein> expression induced by etoposide , teniposide , and UV irradiation ."}285{"id": "284", "text": "A nondegradable mutant of I kappa B blocked both FasL expression and apoptosis induced by DNA damage but not Fas ligation .", "annotated_text": "A <protein>nondegradable mutant</protein> of <protein>I kappa B</protein> blocked both <protein>FasL</protein> expression and apoptosis induced by DNA damage but not Fas ligation ."}286{"id": "285", "text": "These stimuli also induced the stress-activated kinase pathway ( SAPK/JNK ) , which was required for the maximal induction of apoptosis .", "annotated_text": "These stimuli also induced the stress-activated kinase pathway ( SAPK/JNK ) , which was required for the maximal induction of apoptosis ."}287{"id": "286", "text": "A 1.2 kb FasL promoter responded to DNA damage , as well as coexpression with p65 Rel or Fos/Jun .", "annotated_text": "A 1.2 kb <dna>FasL promoter</dna> responded to DNA damage , as well as coexpression with <protein>p65 Rel</protein> or <protein>Fos/Jun</protein> ."}288{"id": "287", "text": "Mutations in the relevant NF-kappa B and AP-1 binding sites eliminated these responses .", "annotated_text": "Mutations in the relevant <dna>NF-kappa B and AP-1 binding sites</dna> eliminated these responses ."}289{"id": "288", "text": "Thus , activation of NF-kappa B and AP-1 contributes to stress-induced apoptosis via the expression of FasL .", "annotated_text": "Thus , activation of <protein>NF-kappa B</protein> and <protein>AP-1</protein> contributes to stress-induced apoptosis via the expression of <protein>FasL</protein> ."}290{"id": "289", "text": "A small , nonpeptidyl mimic of granulocyte-colony-stimulating factor [ see commetns ]", "annotated_text": "A small , nonpeptidyl mimic of <protein>granulocyte-colony-stimulating factor</protein> [ see commetns ]"}291{"id": "290", "text": "A nonpeptidyl small molecule SB 247464 , capable of activating granulocyte-colony-stimulating factor ( G-CSF ) signal transduction pathways , was identified in a high-throughput assay in cultured cells .", "annotated_text": "A nonpeptidyl small molecule SB 247464 , capable of activating <protein>granulocyte-colony-stimulating factor</protein> ( <protein>G-CSF</protein> ) signal transduction pathways , was identified in a high-throughput assay in <cell_type>cultured cells</cell_type> ."}292{"id": "291", "text": "Like G-CSF , SB 247464 induced tyrosine phosphorylation of multiple signaling proteins and stimulated primary murine bone marrow cells to form granulocytic colonies in vitro .", "annotated_text": "Like <protein>G-CSF</protein> , SB 247464 induced tyrosine phosphorylation of <protein>multiple signaling proteins</protein> and stimulated <cell_type>primary murine bone marrow cells</cell_type> to form <cell_type>granulocytic colonies</cell_type> in vitro ."}293{"id": "292", "text": "It also elevated peripheral blood neutrophil counts in mice .", "annotated_text": "It also elevated <cell_type>peripheral blood neutrophil</cell_type> counts in mice ."}294{"id": "293", "text": "The extracellular domain of the murine G-CSF receptor was required for the activity of SB 247464 , suggesting that the compound acts by oligomerizing receptor chains .", "annotated_text": "The extracellular domain of the <protein>murine G-CSF receptor</protein> was required for the activity of SB 247464 , suggesting that the compound acts by <protein>oligomerizing receptor chains</protein> ."}295{"id": "294", "text": "The results indicate that a small molecule can activate a receptor that normally binds a relatively large protein ligand .", "annotated_text": "The results indicate that a small molecule can activate a receptor that normally binds a relatively large protein ligand ."}296{"id": "295", "text": "Minimal residual disease in acute myelogenous leukemia with PML/RAR alpha or AML1/ETO mRNA and phenotypic analysis of possible T and natural killer cells in bone marrow .", "annotated_text": "Minimal residual disease in acute myelogenous leukemia with <protein>PML/RAR alpha</protein> or <rna>AML1/ETO mRNA</rna> and phenotypic analysis of possible <cell_type>T and natural killer cells</cell_type> in bone marrow ."}297{"id": "296", "text": "Here we studied minimal residual disease ( MRD ) of patients with acute myeloid leukemia ( AML ) who have PML/RAR alpha or AML1/ETO as well as the phenotypic analysis of lymphocyte subsets involved in antitumor immunity .", "annotated_text": "Here we studied minimal residual disease ( MRD ) of patients with acute myeloid leukemia ( AML ) who have <protein>PML/RAR alpha</protein> or <protein>AML1/ETO</protein> as well as the phenotypic analysis of <cell_type>lymphocyte subsets</cell_type> involved in antitumor immunity ."}298{"id": "297", "text": "Eight patients in long-term ( LT ; 3 to 15 years ) and 15 patients in short-term ( ST ; up to 3 years ) remission were studied .", "annotated_text": "Eight patients in long-term ( LT ; 3 to 15 years ) and 15 patients in short-term ( ST ; up to 3 years ) remission were studied ."}299{"id": "298", "text": "Using the reverse transcription-polymerase chain reaction ( RT ) assay , the limit of detection was 10 ( -5 ) to 10 ( -6 ) for PML/RAR alpha transcript and 10 ( -4 ) to 10 ( -5 ) for the AML1/ETO transcript .", "annotated_text": "Using the reverse transcription-polymerase chain reaction ( RT ) assay , the limit of detection was 10 ( -5 ) to 10 ( -6 ) for <rna>PML/RAR alpha transcript</rna> and 10 ( -4 ) to 10 ( -5 ) for the <rna>AML1/ETO transcript</rna> ."}300{"id": "299", "text": "Simultaneously , T lymphocyte subsets and NK cells from the peripheral blood ( PB ) and bone marrow ( BM ) were investigated by flow cytometric analysis .", "annotated_text": "Simultaneously , <cell_type>T lymphocyte subsets</cell_type> and <cell_type>NK cells</cell_type> from the peripheral blood ( PB ) and bone marrow ( BM ) were investigated by flow cytometric analysis ."}301{"id": "300", "text": "Four of the eight patients in LT and 7 of the 15 patients in ST remission were MRD-positive .", "annotated_text": "Four of the eight patients in LT and 7 of the 15 patients in ST remission were MRD-positive ."}302{"id": "301", "text": "Although all MRD-positive patients in LT remission are still until now event-free , 3 of the 7 MRD-positive ( MRD+ ) patients in ST remission soon relapsed .", "annotated_text": "Although all MRD-positive patients in LT remission are still until now event-free , 3 of the 7 MRD-positive ( MRD+ ) patients in ST remission soon relapsed ."}303{"id": "302", "text": "The total populations of CD4 + , CD8 + and CD56 + [ possible T-cell and natural killer ( T/NK ) populations ] in the BM of ST patients and MRD+/LT patients were significantly ( p < .01 ) low .", "annotated_text": "The total populations of <protein>CD4</protein> + , <protein>CD8</protein> + and <protein>CD56</protein> + [ possible <cell_type>T-cell and natural killer ( T/NK ) populations</cell_type> ] in the BM of ST patients and MRD+/LT patients were significantly ( p < .01 ) low ."}304{"id": "303", "text": "The CD8+ CD28+ population showed the same tendency ( p < .01-.02 ) .", "annotated_text": "The <cell_type>CD8+ CD28+ population</cell_type> showed the same tendency ( p < .01-.02 ) ."}305{"id": "304", "text": "The T/NK subsets in the BM of MRD-negative ( MRD- ) LT ( MRD-/LT ) patients showed similar numbers of cells as normal volunteers .", "annotated_text": "The <cell_type>T/NK subsets</cell_type> in the BM of MRD-negative ( MRD- ) LT ( MRD-/LT ) patients showed similar numbers of cells as normal volunteers ."}306{"id": "305", "text": "Basically , the total percentage of the CD4+ , CD8+ and CD56+ cell populations in the BM was increased and in the following order : MRD-/LT patients , normal volunteers , MRD+/LT patients and MRD+ or -/ST patients .", "annotated_text": "Basically , the total percentage of the <cell_type>CD4+ , CD8+ and CD56+ cell populations</cell_type> in the BM was increased and in the following order : MRD-/LT patients , normal volunteers , MRD+/LT patients and MRD+ or -/ST patients ."}307{"id": "306", "text": "The percentages of the T/NK-cell subsets in the PB were not significantly different among these groups .", "annotated_text": "The percentages of the <cell_type>T/NK-cell subsets</cell_type> in the PB were not significantly different among these groups ."}308{"id": "307", "text": "Thus , the difference of the possible T/NK-cell phenotype in the BM may strongly influence clinical and molecular remission .", "annotated_text": "Thus , the difference of the possible <cell_type>T/NK-cell</cell_type> phenotype in the BM may strongly influence clinical and molecular remission ."}309{"id": "308", "text": "These results still remain to be confirmed by further studies of the functional anti-tumor immunity of T/NK cells of AML in remission .", "annotated_text": "These results still remain to be confirmed by further studies of the functional anti-tumor immunity of <cell_type>T/NK cells</cell_type> of <cell_type>AML</cell_type> in remission ."}310{"id": "309", "text": "Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-kappaB -dependent activation of human immunodeficiency virus type 1 long terminal repeat in T cells .", "annotated_text": "Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce <protein>NF-kappaB</protein> -dependent activation of <dna>human immunodeficiency virus type 1 long terminal repeat</dna> in <cell_type>T cells</cell_type> ."}311{"id": "310", "text": "Tuberculosis has emerged as an epidemic , extended by the large number of individuals infected with human immunodeficiency virus type 1 ( HIV-1 ) .", "annotated_text": "Tuberculosis has emerged as an epidemic , extended by the large number of individuals infected with human immunodeficiency virus type 1 ( HIV-1 ) ."}312{"id": "311", "text": "The major goal of this study was to determine whether the mycobacterial cell wall component mannose-capped lipoarabinomannan ( ManLAM ) of Mycobacterium tuberculosis ( M. tuberculosis ) could activate transcription of HIV-1 in T cells with the use of an in vitro cell culture system .", "annotated_text": "The major goal of this study was to determine whether the mycobacterial cell wall component mannose-capped lipoarabinomannan ( ManLAM ) of Mycobacterium tuberculosis ( M. tuberculosis ) could activate transcription of HIV-1 in <cell_type>T cells</cell_type> with the use of an in vitro cell culture system ."}313{"id": "312", "text": "These experiments are of prime importance considering that CD4 -expressing T lymphocytes represent the major virus reservoir in the peripheral blood of infected individuals .", "annotated_text": "These experiments are of prime importance considering that <protein>CD4</protein> -expressing <cell_type>T lymphocytes</cell_type> represent the major virus reservoir in the peripheral blood of infected individuals ."}314{"id": "313", "text": "Using the 1G5 cell line harbouring the luciferase reporter gene under the control of the HIV-1 LTR , it was first found that culture protein filtrates ( CFP ) from M. tuberculosis or purified ManLAM could activate HIV-1 LTR-dependent gene expression unlike similarly prepared CFP extracts devoid of ManLAM .", "annotated_text": "Using the <cell_line>1G5 cell line</cell_line> harbouring the luciferase reporter gene under the control of the <dna>HIV-1 LTR</dna> , it was first found that culture protein filtrates ( CFP ) from M. tuberculosis or purified ManLAM could activate <dna>HIV-1 LTR-dependent gene</dna> expression unlike similarly prepared CFP extracts devoid of ManLAM ."}315{"id": "314", "text": "The implication of protein tyrosine kinase ( s ) , protein kinase A and/or protein kinase C was highlighted by the abrogation of the ManLAM-mediated activation of HIV-1 LTR-driven gene expression using herbimycin A and H7 .", "annotated_text": "The implication of <protein>protein tyrosine kinase ( s )</protein> , <protein>protein kinase A</protein> and/or <protein>protein kinase C</protein> was highlighted by the abrogation of the ManLAM-mediated activation of HIV-1 LTR-driven gene expression using herbimycin A and H7 ."}316{"id": "315", "text": "It was also determined , using electrophoresis mobility shift assays , that M. tuberculosis ManLAM led to the nuclear translocation of the transcription factor NF-kappaB .", "annotated_text": "It was also determined , using electrophoresis mobility shift assays , that M. tuberculosis ManLAM led to the nuclear translocation of the <protein>transcription factor NF-kappaB</protein> ."}317{"id": "316", "text": "M. tuberculosis ManLAM resulted in clear induction of the luciferase gene placed under the control of the wild-type , but not the kappaB-mutated , HIV-1 LTR region .", "annotated_text": "M. tuberculosis ManLAM resulted in clear induction of the <dna>luciferase gene</dna> placed under the control of the <dna>wild-type , but not the kappaB-mutated , HIV-1 LTR region</dna> ."}318{"id": "317", "text": "Finally , the ManLAM-mediated activation of HIV-1 LTR transcription was found to be independent of the autocrine or paracrine action of endogenous TNF-alpha .", "annotated_text": "Finally , the ManLAM-mediated activation of HIV-1 LTR transcription was found to be independent of the autocrine or paracrine action of <protein>endogenous TNF-alpha</protein> ."}319{"id": "318", "text": "The results suggest that M. tuberculosis can upregulate HIV-1 expression in T cells and could thus have the potential to influence the pathogenesis of HIV-1 infection .", "annotated_text": "The results suggest that M. tuberculosis can upregulate HIV-1 expression in <cell_type>T cells</cell_type> and could thus have the potential to influence the pathogenesis of HIV-1 infection ."}320{"id": "319", "text": "Human immunodeficiency virus type 1 long terminal repeat quasispecies differ in basal transcription and nuclear factor recruitment in human glial cells and lymphocytes .", "annotated_text": "<dna>Human immunodeficiency virus type 1 long terminal repeat</dna> quasispecies differ in basal transcription and nuclear factor recruitment in <cell_type>human glial cells and lymphocytes</cell_type> ."}321{"id": "320", "text": "The generation of genomic diversity during the course of infection has the potential to affect all aspects of HIV-1 replication , including expression of the proviral genome .", "annotated_text": "The generation of genomic diversity during the course of infection has the potential to affect all aspects of HIV-1 replication , including expression of the proviral genome ."}322{"id": "321", "text": "To gain a better understanding of the impact of long terminal repeat ( LTR ) sequence diversity on LTR-directed gene expression in cells of the central nervous system ( CNS ) and immune system , we amplified and cloned LTRs from proviral DNA in HIV-1-infected peripheral blood .", "annotated_text": "To gain a better understanding of the impact of <dna>long terminal repeat</dna> ( <dna>LTR</dna> ) sequence diversity on <dna>LTR-directed gene</dna> expression in cells of the central nervous system ( CNS ) and immune system , we amplified and cloned <dna>LTRs</dna> from proviral DNA in HIV-1-infected peripheral blood ."}323{"id": "322", "text": "Sequence analysis of nineteen LTRs cloned from 2 adult and 3 pediatric patients revealed an average of 33 nucleotide changes ( with respect to the sequence of the LAI LTR ) within the 455-bp U3 region .", "annotated_text": "Sequence analysis of nineteen <dna>LTRs</dna> cloned from 2 adult and 3 pediatric patients revealed an average of 33 nucleotide changes ( with respect to the sequence of the <dna>LAI LTR</dna> ) within the <dna>455-bp U3 region</dna> ."}324{"id": "323", "text": "Transient expression analyses in cells of neuroglial and lymphocytic origin demonstrated that some of these LTRs had activities which varied significantly from the LAI LTR in U-373 MG cells ( an astrocytoma cell line ) as well as in Jurkat cells ( a CD4-positive lymphocyte cell line ) .", "annotated_text": "Transient expression analyses in cells of neuroglial and lymphocytic origin demonstrated that some of these <dna>LTRs</dna> had activities which varied significantly from the <dna>LAI LTR</dna> in <cell_line>U-373 MG cells</cell_line> ( an <cell_line>astrocytoma cell line</cell_line> ) as well as in <cell_line>Jurkat cells</cell_line> ( a <cell_line>CD4-positive lymphocyte cell line</cell_line> ) ."}325{"id": "324", "text": "While LTRs which demonstrated the highest activities in U-373 MG cells also yielded high activities in Jurkat cells , the LTRs were generally more active in Jurkat cells when compared to the LAI LTR .", "annotated_text": "While <dna>LTRs</dna> which demonstrated the highest activities in <cell_line>U-373 MG cells</cell_line> also yielded high activities in <cell_line>Jurkat cells</cell_line> , the <dna>LTRs</dna> were generally more active in <cell_line>Jurkat cells</cell_line> when compared to the <dna>LAI LTR</dna> ."}326{"id": "325", "text": "Differences in LTR sequence also resulted in differences in transcription factor recruitment to cis-acting sites within the U3 region of the LTR , as demonstrated by electrophoretic mobility shift assays .", "annotated_text": "Differences in <dna>LTR sequence</dna> also resulted in differences in transcription factor recruitment to <dna>cis-acting sites</dna> within the <dna>U3 region</dna> of the <dna>LTR</dna> , as demonstrated by electrophoretic mobility shift assays ."}327{"id": "326", "text": "In particular , naturally occurring sequence variation impacted transcription factor binding to an activating transcription factor / cAMP response element binding ( ATF / CREB ) binding site ( located between the LEF-1 and distal NF-kappaB transcription factor binding sites ) that we identified in previous studies of the HIV-1 LTR .", "annotated_text": "In particular , naturally occurring sequence variation impacted <protein>transcription factor</protein> binding to an <protein>activating transcription factor</protein> / <protein>cAMP response element binding</protein> ( <protein>ATF</protein> / <protein>CREB</protein> ) binding site ( located between the <dna>LEF-1 and distal NF-kappaB transcription factor binding sites</dna> ) that we identified in previous studies of the <dna>HIV-1 LTR</dna> ."}328{"id": "327", "text": "These findings suggest that LTR sequence changes can significantly affect basal LTR function and transcription factor recruitment , which may , in turn , alter the course of viral replication in cells of CNS and immune system origin .", "annotated_text": "These findings suggest that <dna>LTR sequence</dna> changes can significantly affect basal LTR function and transcription factor recruitment , which may , in turn , alter the course of viral replication in cells of CNS and immune system origin ."}329{"id": "328", "text": "HMG box containing transcription factors in lymphocyte differentiation .", "annotated_text": "<protein>HMG box containing transcription factors</protein> in <cell_type>lymphocyte</cell_type> differentiation ."}330{"id": "329", "text": "The identification of the mammalian sex-determining gene Sry has led to the discovery of a large family of related ( ' HMG box ' ) transcription factors that control developmental events in yeast , C. elegans , Drosophila and vertebrates .", "annotated_text": "The identification of the <dna>mammalian sex-determining gene Sry</dna> has led to the discovery of a large family of related ( ' <protein>HMG box</protein> ' ) <protein>transcription factors</protein> that control developmental events in yeast , C. elegans , Drosophila and vertebrates ."}331{"id": "330", "text": "In lymphocyte differentiation , several HMG box proteins play a decisive role .", "annotated_text": "In <cell_type>lymphocyte</cell_type> differentiation , several <protein>HMG box proteins</protein> play a decisive role ."}332{"id": "331", "text": "Sox-4 is important for very early B-cell differentiation , while TCF-1 / LEF-1 play a crucial role in early thymocyte development .", "annotated_text": "<protein>Sox-4</protein> is important for very early B-cell differentiation , while <protein>TCF-1</protein> / <protein>LEF-1</protein> play a crucial role in early thymocyte development ."}333{"id": "332", "text": "TCF/LEF proteins have recently been found to constitute a downstream component of the Wingless/Wnt signal transduction pathway .", "annotated_text": "<protein>TCF/LEF proteins</protein> have recently been found to constitute a downstream component of the Wingless/Wnt signal transduction pathway ."}334{"id": "333", "text": "In flies , this pathway controls segment polarity ; in Xenopus it controls the definition of the body axis .", "annotated_text": "In flies , this pathway controls segment polarity ; in Xenopus it controls the definition of the body axis ."}335{"id": "334", "text": "Deregulation of the pathway occurs in several human tumors .", "annotated_text": "Deregulation of the pathway occurs in several <cell_type>human tumors</cell_type> ."}336{"id": "335", "text": "These insights in the molecular events that are involved in TCF/LEF function in these organisms may eventually lead to the understanding of the function of these HMG box proteins in lymphoid development", "annotated_text": "These insights in the molecular events that are involved in <protein>TCF/LEF</protein> function in these organisms may eventually lead to the understanding of the function of these <protein>HMG box proteins</protein> in lymphoid development"}337{"id": "336", "text": "Transcriptional regulation by C/EBP alpha and -beta in the expression of the gene for the MRP14 myeloid calcium binding protein .", "annotated_text": "Transcriptional regulation by <protein>C/EBP alpha and -beta</protein> in the expression of the gene for the <protein>MRP14 myeloid calcium binding protein</protein> ."}338{"id": "337", "text": "Transcriptional regulation of the gene for the myeloid calcium binding protein , MRP14 , was investigated in human monocytic leukemia cell lines .", "annotated_text": "Transcriptional regulation of the gene for the <protein>myeloid calcium binding protein</protein> , <protein>MRP14</protein> , was investigated in <cell_line>human monocytic leukemia cell lines</cell_line> ."}339{"id": "338", "text": "The MRP14 gene was not expressed in monoblastic ML-1 cells , promonocytic U-937 cells , or promyelocytic HL-60 cells .", "annotated_text": "The <dna>MRP14 gene</dna> was not expressed in <cell_line>monoblastic ML-1 cells</cell_line> , <cell_line>promonocytic U-937 cells</cell_line> , or <cell_line>promyelocytic HL-60 cells</cell_line> ."}340{"id": "339", "text": "On the other hand , the gene was expressed in monocytic THP-1 cells and in the HL-60 cells treated with 1 , 25-dihydroxyvitamin D3 ( VD3 ) .", "annotated_text": "On the other hand , the gene was expressed in <cell_line>monocytic THP-1 cells</cell_line> and in the <cell_line>HL-60 cells</cell_line> treated with 1 , 25-dihydroxyvitamin D3 ( VD3 ) ."}341{"id": "340", "text": "The level of MRP14 in VD3-treated HL-60 cells was two-fold higher than that in THP-1 cells .", "annotated_text": "The level of <protein>MRP14</protein> in VD3-treated <cell_line>HL-60 cells</cell_line> was two-fold higher than that in <cell_line>THP-1 cells</cell_line> ."}342{"id": "341", "text": "Among several known transcription factor binding motifs , nuclear protein ( s ) of VD3-treated HL-60 cells and THP-1 cells bound to the CCAAT/enhancer binding protein ( C/EBP ) -binding motif that was located in the upstream region of the MRP14 gene ( -81 ) , as evidenced by the competitive gel mobility-shift assay .", "annotated_text": "Among several known <dna>transcription factor binding motifs</dna> , <protein>nuclear protein ( s )</protein> of <cell_line>VD3-treated HL-60 cells and THP-1 cells</cell_line> bound to the <dna>CCAAT/enhancer binding protein ( C/EBP ) -binding motif</dna> that was located in the <dna>upstream region</dna> of the <dna>MRP14 gene</dna> ( -81 ) , as evidenced by the competitive gel mobility-shift assay ."}343{"id": "342", "text": "An antibody for C/EBP alpha super-shifted the nucleoprotein complex in THP-1 cells but not in the VD3-treated HL-60 cells , whereas an antibody for C/EBP beta blocked the formation of the complex with the nuclear factor of the HL-60 cells but not with that of THP-1 cells .", "annotated_text": "An antibody for <protein>C/EBP alpha</protein> super-shifted the <protein>nucleoprotein complex</protein> in <cell_line>THP-1 cells</cell_line> but not in the <cell_line>VD3-treated HL-60 cells</cell_line> , whereas an antibody for <protein>C/EBP beta</protein> blocked the formation of the complex with the <protein>nuclear factor</protein> of the <cell_line>HL-60 cells</cell_line> but not with that of <cell_line>THP-1 cells</cell_line> ."}344{"id": "343", "text": "An anti-C/EBP delta antibody had no effect on the complex in either cell .", "annotated_text": "An <protein>anti-C/EBP delta antibody</protein> had no effect on the complex in either cell ."}345{"id": "344", "text": "Thus , it was concluded that C/EBP alpha and -beta were able to bind to the C/EBP motif , and that C/EBP alpha bound to the motif in THP-1 cells and C/EBP beta bound to that in the VD3-treated HL-60 cells .", "annotated_text": "Thus , it was concluded that <protein>C/EBP alpha and -beta</protein> were able to bind to the <protein>C/EBP motif</protein> , and that <protein>C/EBP alpha</protein> bound to the motif in <cell_line>THP-1 cells</cell_line> and <protein>C/EBP beta</protein> bound to that in the <cell_line>VD3-treated HL-60 cells</cell_line> ."}346{"id": "345", "text": "Furthermore , to examine the transcriptional activity of the C/EBP motif , we transfected several constructed luciferase reporter DNAs into HL-60 cells and THP-1 cells .", "annotated_text": "Furthermore , to examine the transcriptional activity of the <protein>C/EBP motif</protein> , we transfected several constructed <dna>luciferase reporter DNAs</dna> into <cell_line>HL-60 cells</cell_line> and <cell_line>THP-1 cells</cell_line> ."}347{"id": "346", "text": "The luciferase activity of the C/EBP motif in HL-60 cells was increased by VD3 treatment .", "annotated_text": "The luciferase activity of the <protein>C/EBP motif</protein> in <cell_line>HL-60 cells</cell_line> was increased by VD3 treatment ."}348{"id": "347", "text": "The C/EBP motif in the MRP14 gene was confirmed to function as a regulatory region in VD3-treated HL-60 cells and THP-1 cells by the assay .", "annotated_text": "The <protein>C/EBP motif</protein> in the <dna>MRP14 gene</dna> was confirmed to function as a regulatory region in <cell_line>VD3-treated HL-60 cells and THP-1 cells</cell_line> by the assay ."}349{"id": "348", "text": "Since C/EBP beta was also detected in VD3-untreated HL-60 cells by immunoblotting , VD3 activated C/EBP beta to bind to the motif , probably through post-translational modification .", "annotated_text": "Since <protein>C/EBP beta</protein> was also detected in <cell_line>VD3-untreated HL-60 cells</cell_line> by immunoblotting , VD3 activated <protein>C/EBP beta</protein> to bind to the motif , probably through post-translational modification ."}350{"id": "349", "text": "Patients with high-risk myelodysplastic syndrome can have polyclonal or clonal haemopoiesis in complete haematological remission .", "annotated_text": "Patients with high-risk myelodysplastic syndrome can have polyclonal or clonal haemopoiesis in complete haematological remission ."}351{"id": "350", "text": "The clonality of mature peripheral blood-derived myeloid and lymphoid cells and bone marrow haemopoietic progenitors from 18 females with myelodysplasia ( MDS ) ( five refractory anaemia , RA ; one RA with ringed sideroblasts , RARS ; three chronic myelomonocytic leukaemia , CMML ; four RA with excess of blasts , RAEB ; five RAEB in transformation , RAEB-t ) was studied by X-chromosome inactivation analysis .", "annotated_text": "The clonality of <cell_type>mature peripheral blood-derived myeloid and lymphoid cells</cell_type> and <cell_type>bone marrow haemopoietic progenitors</cell_type> from 18 females with myelodysplasia ( MDS ) ( five refractory anaemia , RA ; one RA with <cell_type>ringed sideroblasts</cell_type> , RARS ; three chronic myelomonocytic leukaemia , CMML ; four RA with excess of blasts , RAEB ; five RAEB in transformation , RAEB-t ) was studied by <dna>X-chromosome</dna> inactivation analysis ."}352{"id": "351", "text": "Using the human androgen-receptor ( HUMARA ) assay , we analysed the clonal patterns of highly purified immature CD34+ 38- and committed CD34+ 38+ marrow-derived progenitors , and CD16+ 14- granulocytes , CD14+ monocytes , CD3+ T and CD19+ B lymphocytes from peripheral blood .", "annotated_text": "Using the human androgen-receptor ( HUMARA ) assay , we analysed the clonal patterns of <cell_type>highly purified immature CD34+ 38- and committed CD34+ 38+ marrow-derived progenitors</cell_type> , and <cell_type>CD16+ 14- granulocytes</cell_type> , <cell_type>CD14+ monocytes</cell_type> , <cell_type>CD3+ T and CD19+ B lymphocytes</cell_type> from peripheral blood ."}353{"id": "352", "text": "In high-risk patients ( RAEB , RAEB-t ) , clonality analysis was performed before and after intensive remission-induction treatment .", "annotated_text": "In high-risk patients ( RAEB , RAEB-t ) , clonality analysis was performed before and after intensive remission-induction treatment ."}354{"id": "353", "text": "All patients , except one with RA , had predominance of a single clone in their granulocytes and monocytes .", "annotated_text": "All patients , except one with RA , had predominance of a single clone in their <cell_type>granulocytes</cell_type> and <cell_type>monocytes</cell_type> ."}355{"id": "354", "text": "The same clonal pattern was found in CD34+ progenitor cells .", "annotated_text": "The same clonal pattern was found in <cell_type>CD34+ progenitor cells</cell_type> ."}356{"id": "355", "text": "In contrast , CD3+ T lymphocytes were polyclonal or oligoclonal in 14/18 patients .", "annotated_text": "In contrast , <cell_type>CD3+ T lymphocytes</cell_type> were polyclonal or oligoclonal in 14/18 patients ."}357{"id": "356", "text": "X-chromosome inactivation patterns of CD19+ B cells were highly concordant with CD3+ T cells except for two patients ( one RA , one CMML ) with monoclonal B and polyclonal T lymphocytes , therefore suggesting a clonal mutation in a progenitor common to the myeloid and B-lymphoid lineages or the coexistence of MDS and a B-cell disorder in these particular patients .", "annotated_text": "<dna>X-chromosome</dna> inactivation patterns of <cell_type>CD19+ B cells</cell_type> were highly concordant with <cell_type>CD3+ T cells</cell_type> except for two patients ( one RA , one CMML ) with <cell_type>monoclonal B and polyclonal T lymphocytes</cell_type> , therefore suggesting a clonal mutation in a <cell_type>progenitor</cell_type> common to the <cell_type>myeloid and B-lymphoid lineages</cell_type> or the coexistence of MDS and a B-cell disorder in these particular patients ."}358{"id": "357", "text": "After high-dose non-myeloablative chemotherapy , polyclonal haemopoiesis was reinstalled in the mature myeloid cells and immature and committed marrow progenitors in three of four patients achieving complete haematological remission .", "annotated_text": "After high-dose non-myeloablative chemotherapy , polyclonal haemopoiesis was reinstalled in the <cell_type>mature myeloid cells</cell_type> and immature and <cell_type>committed marrow progenitors</cell_type> in three of four patients achieving complete haematological remission ."}359{"id": "358", "text": "Therefore we conclude that most haematological remissions in MDS are associated with restoration of polyclonal haemopoiesis .", "annotated_text": "Therefore we conclude that most haematological remissions in MDS are associated with restoration of polyclonal haemopoiesis ."}360{"id": "359", "text": "Prominent sex steroid metabolism in human lymphocytes .", "annotated_text": "Prominent sex steroid metabolism in <cell_type>human lymphocytes</cell_type> ."}361{"id": "360", "text": "Steroid metabolism was investigated in cultured human B-lymphoblastoid cells ( B-LCL ) , and peripheral blood T and B cells .", "annotated_text": "Steroid metabolism was investigated in <cell_line>cultured human B-lymphoblastoid cells</cell_line> ( <cell_line>B-LCL</cell_line> ) , and <cell_type>peripheral blood T and B cells</cell_type> ."}362{"id": "361", "text": "Gene expression was examined by reverse-transcription polymerase chain reaction amplification ( RT-PCR ) .", "annotated_text": "Gene expression was examined by reverse-transcription polymerase chain reaction amplification ( RT-PCR ) ."}363{"id": "362", "text": "Appropriate sized transcripts were detected in both cultured and fresh peripheral lymphocytes for CYP11A , CYP17 , HSD11L ( 11beta-hydroxysteroid dehydrogenase I ) , HSD17B1 ( 17beta-hydroxysteroid dehydrogenase type I ) and SRD5A1 ( 5alpha-reductase I ) .", "annotated_text": "Appropriate sized <rna>transcripts</rna> were detected in both cultured and fresh <cell_type>peripheral lymphocytes</cell_type> for <protein>CYP11A</protein> , <protein>CYP17</protein> , <protein>HSD11L</protein> ( <protein>11beta-hydroxysteroid dehydrogenase I</protein> ) , <protein>HSD17B1</protein> ( <protein>17beta-hydroxysteroid dehydrogenase type I</protein> ) and <protein>SRD5A1</protein> ( <protein>5alpha-reductase I</protein> ) ."}364{"id": "363", "text": "B-LCL , but not T and B cells , expressed CYP11B .", "annotated_text": "B-LCL , but not <cell_type>T and B cells</cell_type> , expressed <protein>CYP11B</protein> ."}365{"id": "364", "text": "There was minimal expression of HSD3B1 and HSD3B2 ( 3beta-hydroxysteroid dehydrogenase I and II ) in B-LCL and T cells .", "annotated_text": "There was minimal expression of <protein>HSD3B1</protein> and <protein>HSD3B2</protein> ( <protein>3beta-hydroxysteroid dehydrogenase I and II</protein> ) in <cell_line>B-LCL</cell_line> and <cell_type>T cells</cell_type> ."}366{"id": "365", "text": "Transcripts for CYP19 and HSD11K were not detected .", "annotated_text": "Transcripts for <protein>CYP19</protein> and <protein>HSD11K</protein> were not detected ."}367{"id": "366", "text": "Corresponding enzymatic activity was detectable only for 17-hydroxysteroid dehydrogenase and 5alpha-reductase , respectively producing testosterone and 5alpha-dihydrotestosterone .", "annotated_text": "Corresponding enzymatic activity was detectable only for <protein>17-hydroxysteroid dehydrogenase</protein> and <protein>5alpha-reductase</protein> , respectively producing testosterone and 5alpha-dihydrotestosterone ."}368{"id": "367", "text": "Steroid identities were confirmed by gas chromatography/mass spectrometry ( GC/MS ) .", "annotated_text": "Steroid identities were confirmed by gas chromatography/mass spectrometry ( GC/MS ) ."}369{"id": "368", "text": "One metabolite thought to be deoxycorticosterone was identified by GC/MS as 6alpha-hydroxypregnanolone .", "annotated_text": "One metabolite thought to be deoxycorticosterone was identified by GC/MS as 6alpha-hydroxypregnanolone ."}370{"id": "369", "text": "It was concluded that sex hormone metabolism , including androgen synthesis , occurs in lymphocytes , and may modulate immune response .", "annotated_text": "It was concluded that sex hormone metabolism , including androgen synthesis , occurs in lymphocytes , and may modulate immune response ."}371{"id": "370", "text": "Human white blood cells and hair follicles are good sources of mRNA for the pterin carbinolamine dehydratase/dimerization cofactor of HNF1 for mutation detection .", "annotated_text": "<cell_type>Human white blood cells</cell_type> and hair follicles are good sources of <rna>mRNA</rna> for the <protein>pterin carbinolamine dehydratase/dimerization cofactor</protein> of <protein>HNF1</protein> for mutation detection ."}372{"id": "371", "text": "Pterin carbinolamine dehydratase/dimerization cofactor of HNF1 ( PCD/DCoH ) is a protein that has a dual function .", "annotated_text": "<protein>Pterin carbinolamine dehydratase/dimerization cofactor</protein> of <protein>HNF1</protein> ( <protein>PCD/DCoH</protein> ) is a protein that has a dual function ."}373{"id": "372", "text": "It is a pterin 4alpha-carbinolamine dehydratase that is involved in the regeneration of the cofactor tetrahydrobiopterin during the phenylalanine hydroxylase- catalyzed hydroxylation of phenylalanine .", "annotated_text": "It is a <protein>pterin 4alpha-carbinolamine dehydratase</protein> that is involved in the regeneration of the <protein>cofactor tetrahydrobiopterin</protein> during the phenylalanine hydroxylase- catalyzed hydroxylation of phenylalanine ."}374{"id": "373", "text": "In addition , it is the dimerization cofactor of HNF1 that is able to activate the transcriptional activity of HNF1 .", "annotated_text": "In addition , it is the dimerization cofactor of <protein>HNF1</protein> that is able to activate the transcriptional activity of <protein>HNF1</protein> ."}375{"id": "374", "text": "Deficiencies in the gene for this dual functional protein result in hyperphenylalaninemia .", "annotated_text": "Deficiencies in the gene for this <protein>dual functional protein</protein> result in hyperphenylalaninemia ."}376{"id": "375", "text": "Here we report for the first time that the PCD/DCoH mRNA is present in human white blood cells and hair follicles .", "annotated_text": "Here we report for the first time that the <rna>PCD/DCoH mRNA</rna> is present in <cell_type>human white blood cells</cell_type> and hair follicles ."}377{"id": "376", "text": "Taking advantage of this finding , a sensitive , rapid and convenient method for screening mutations occurring in the coding region of this gene has been described .", "annotated_text": "Taking advantage of this finding , a sensitive , rapid and convenient method for screening mutations occurring in the coding region of this gene has been described ."}378{"id": "377", "text": "Copyright 1998 Academic Press .", "annotated_text": "Copyright 1998 Academic Press ."}379{"id": "378", "text": "Biochemical characterization of the NF-Y transcription factor complex during B lymphocyte development .", "annotated_text": "Biochemical characterization of the <protein>NF-Y transcription factor complex</protein> during B lymphocyte development ."}380{"id": "379", "text": "The transcription factor , NF-Y , plays a critical role in tissue-specific major histocompatibility complex class II gene transcription .", "annotated_text": "The <protein>transcription factor</protein> , <protein>NF-Y</protein> , plays a critical role in tissue-specific <dna>major histocompatibility complex class II gene</dna> transcription ."}381{"id": "380", "text": "In this report the biochemical properties of the heterotrimeric NF-Y complex have been characterized during stage-specific B-cell development , and in several class II- mutant B-cell lines , which represent distinct bare lymphocyte syndrome class II genetic complementation groups .", "annotated_text": "In this report the biochemical properties of the <protein>heterotrimeric NF-Y complex</protein> have been characterized during stage-specific B-cell development , and in several <cell_line>class II- mutant B-cell lines</cell_line> , which represent distinct bare lymphocyte syndrome class II genetic complementation groups ."}382{"id": "381", "text": "The NF-Y complex derived from class II+ mature B-cells bound with high affinity to anion exchangers , and eluted as an intact trimeric complex , whereas , NF-Y derived from class II- plasma B-cells , and from bare lymphocyte syndrome group II cell lines , RJ2.2.5 and RM3 , dissociated into discrete NF-YA and NF-YB : C subunit fractions .", "annotated_text": "The <protein>NF-Y complex</protein> derived from <cell_type>class II+ mature B-cells</cell_type> bound with high affinity to <protein>anion exchangers</protein> , and eluted as an intact <protein>trimeric complex</protein> , whereas , <protein>NF-Y</protein> derived from <cell_type>class II- plasma B-cells</cell_type> , and from <cell_line>bare lymphocyte syndrome group II cell lines</cell_line> , <cell_line>RJ2.2.5</cell_line> and <cell_line>RM3</cell_line> , dissociated into discrete <protein>NF-YA</protein> and <protein>NF-YB : C</protein> <protein>subunit fractions</protein> ."}383{"id": "382", "text": "Recombination of the MPC11 plasma B-cell derived NF-Y A : B : C complex with the low molecular mass protein fraction , NF-Y-associated factors ( YAFs ) , derived from mature A20 B-cell nuclei , conferred high affinity anion exchange binding to NF-Y as an intact trimeric complex .", "annotated_text": "Recombination of the <protein>MPC11 plasma B-cell derived NF-Y A : B : C complex</protein> with the low molecular mass protein fraction , <protein>NF-Y-associated factors</protein> ( <protein>YAFs</protein> ) , derived from mature A20 B-cell nuclei , conferred high affinity anion exchange binding to <protein>NF-Y</protein> as an <protein>intact trimeric complex</protein> ."}384{"id": "383", "text": "Recombination of the native NF-YA : B : C complex with the transcriptional cofactor , PC4 , likewise conferred high affinity NF-Y binding to anion exchangers , and stabilized NF-Y interaction with CCAAT-box DNA motifs in vitro .", "annotated_text": "Recombination of the <protein>native NF-YA : B : C complex</protein> with the <protein>transcriptional cofactor</protein> , <protein>PC4</protein> , likewise conferred <protein>high affinity NF-Y</protein> binding to <protein>anion exchangers</protein> , and stabilized <protein>NF-Y</protein> interaction with <dna>CCAAT-box DNA motifs</dna> in vitro ."}385{"id": "384", "text": "Interaction between PC4 and NF-Y was mapped to the C-terminal region of PC4 , and the subunit interaction subdomain of the highly conserved DNA binding-subunit interaction domain ( DBD ) of NF-YA .", "annotated_text": "Interaction between <protein>PC4</protein> and <protein>NF-Y</protein> was mapped to the <protein>C-terminal region</protein> of <protein>PC4</protein> , and the <protein>subunit interaction subdomain</protein> of the <protein>highly conserved DNA binding-subunit interaction domain</protein> ( <protein>DBD</protein> ) of <protein>NF-YA</protein> ."}386{"id": "385", "text": "These results suggest that in class II+ mature B-cells NF-Y is associated with the protein cofactor , PC4 , which may play an important role in NF-Y-mediated transcriptional control of class II genes .", "annotated_text": "These results suggest that in <cell_type>class II+ mature B-cells</cell_type> <protein>NF-Y</protein> is associated with the protein cofactor , <protein>PC4</protein> , which may play an important role in NF-Y-mediated transcriptional control of <dna>class II genes</dna> ."}387{"id": "386", "text": "Arrest of B lymphocyte terminal differentiation by CD40 signaling : mechanism for lack of antibody-secreting cells in germinal centers .", "annotated_text": "Arrest of B lymphocyte terminal differentiation by CD40 signaling : mechanism for lack of <cell_type>antibody-secreting cells</cell_type> in germinal centers ."}388{"id": "387", "text": "Despite extensive research , the role of CD40 signaling in B cell terminal differentiation remains controversial .", "annotated_text": "Despite extensive research , the role of <protein>CD40</protein> signaling in B cell terminal differentiation remains controversial ."}389{"id": "388", "text": "Here we show that CD40 engagement arrests B cell differentiation prior to plasma cell formation .", "annotated_text": "Here we show that <protein>CD40</protein> engagement arrests B cell differentiation prior to plasma cell formation ."}390{"id": "389", "text": "This arrest is manifested at a molecular level as a reduction in mRNA levels of secretory immunoglobulin gene products such as mu ( s ) and J chain as well as the loss of the transcriptional regulator BLIMP-1 .", "annotated_text": "This arrest is manifested at a molecular level as a reduction in mRNA levels of secretory immunoglobulin gene products such as mu ( s ) and J chain as well as the loss of the <protein>transcriptional regulator</protein> <protein>BLIMP-1</protein> ."}391{"id": "390", "text": "Furthermore , the inhibition of B cell differentiation by CD40 engagement could not be overcome by either mitogens or cytokines , but could be reversed by antibodies that interfere with the CD40 / gp39 interaction .", "annotated_text": "Furthermore , the inhibition of B cell differentiation by <protein>CD40</protein> engagement could not be overcome by either <protein>mitogens</protein> or <protein>cytokines</protein> , but could be reversed by antibodies that interfere with the <protein>CD40</protein> / <protein>gp39</protein> interaction ."}392{"id": "391", "text": "These data suggest that secretory immunoglobulin is not produced by B cells that are actively engaged by gp39-expressing T cells .", "annotated_text": "These data suggest that secretory immunoglobulin is not produced by <cell_type>B cells</cell_type> that are actively engaged by <cell_type>gp39-expressing T cells</cell_type> ."}393{"id": "392", "text": "A positively charged alpha-lipoic acid analogue with increased cellular uptake and more potent immunomodulatory activity .", "annotated_text": "A positively charged alpha-lipoic acid analogue with increased cellular uptake and more potent immunomodulatory activity ."}394{"id": "393", "text": "alpha-Lipoic acid ( LA ) is taken up by cells and reduced to its potent dithiol form , dihydrolipoate ( DHLA ) , much of which is rapidly effluxed out from cells .", "annotated_text": "alpha-Lipoic acid ( LA ) is taken up by cells and reduced to its potent dithiol form , dihydrolipoate ( DHLA ) , much of which is rapidly effluxed out from cells ."}395{"id": "394", "text": "To improve retention in cells , the LA molecule was modified to confer a positive charge at physiological pH .", "annotated_text": "To improve retention in cells , the LA molecule was modified to confer a positive charge at physiological pH ."}396{"id": "395", "text": "N , N-dimethyl , N'-2-amidoethyl-lipoate was synthesized .", "annotated_text": "N , N-dimethyl , N'-2-amidoethyl-lipoate was synthesized ."}397{"id": "396", "text": "The protonated form of the new molecule is referred to as LA-Plus .", "annotated_text": "The protonated form of the new molecule is referred to as LA-Plus ."}398{"id": "397", "text": "The uptake of LA-Plus by human Wurzburg T cells was higher compared to that of LA .", "annotated_text": "The uptake of LA-Plus by <cell_type>human Wurzburg T cells</cell_type> was higher compared to that of LA ."}399{"id": "398", "text": "Several-fold higher amounts of DHLA-Plus , the corresponding reduced form of LA-Plus , were detected in LA-Plus treated cells compared to the amount of DHLA found in cells treated with LA .", "annotated_text": "Several-fold higher amounts of DHLA-Plus , the corresponding reduced form of LA-Plus , were detected in LA-Plus treated cells compared to the amount of DHLA found in cells treated with LA ."}400{"id": "399", "text": "At 100 microM , LA did not but LA-Plus inhibited H2O2 induced NF-kappaB activation and NF-kappaB directed IL-2 receptor expression .", "annotated_text": "At 100 microM , LA did not but LA-Plus inhibited H2O2 induced <protein>NF-kappaB</protein> activation and <protein>NF-kappaB</protein> directed <protein>IL-2 receptor</protein> expression ."}401{"id": "400", "text": "Both LA and LA-Plus synergised with selenium in inhibiting H2O2 induced NF-kappaB activation .", "annotated_text": "Both LA and LA-Plus synergised with selenium in inhibiting H2O2 induced <protein>NF-kappaB</protein> activation ."}402{"id": "401", "text": "At 150 microM LA-Plus , but not LA , inhibited TNFalpha induced NF-kappaB activation .", "annotated_text": "At 150 microM LA-Plus , but not LA , inhibited <protein>TNFalpha</protein> induced <protein>NF-kappaB</protein> activation ."}403{"id": "402", "text": "At 5 microM LA-Plus , but not LA , protected against both spontaneous and etoposide induced apoptosis in rat thymocytes .", "annotated_text": "At 5 microM LA-Plus , but not LA , protected against both spontaneous and etoposide induced apoptosis in <cell_type>rat thymocytes</cell_type> ."}404{"id": "403", "text": "LA-Plus is thus an improved form of LA with increased therapeutic potential .", "annotated_text": "LA-Plus is thus an improved form of LA with increased therapeutic potential ."}405{"id": "404", "text": "Copyright 1998 Academic Press .", "annotated_text": "Copyright 1998 Academic Press ."}406{"id": "405", "text": "Carrier identification in X-linked immunodeficiency diseases .", "annotated_text": "Carrier identification in X-linked immunodeficiency diseases ."}407{"id": "406", "text": "OBJECTIVE : Carrier identification in X-linked immunodeficiency disorders can be based on the demonstration of non-random X inactivation ( NRXI ) in affected blood cell lineages when growth is impaired in cells expressing the abnormal gene .", "annotated_text": "OBJECTIVE : Carrier identification in X-linked immunodeficiency disorders can be based on the demonstration of non-random X inactivation ( NRXI ) in <cell_type>affected blood cell lineages</cell_type> when growth is impaired in cells expressing the <dna>abnormal gene</dna> ."}408{"id": "407", "text": "We examined the utility of seeking evidence of NRXI to test the carrier status of women in families affected by X-linked severe combined immunodeficiency ( XSCID ) and X-linked hypogammaglobulinaemia ( XLH ) , to identify as carriers the mothers of boys with SCID or hypogammaglobulinaemia whose phenotype suggested X-linkage and to infer X-linkage in boys with SCID or hypogammaglobulinaemia whose disease was not clearly X-linked on the basis either of family history or clinical and immunological characteristics .", "annotated_text": "We examined the utility of seeking evidence of NRXI to test the carrier status of women in families affected by X-linked severe combined immunodeficiency ( XSCID ) and X-linked hypogammaglobulinaemia ( XLH ) , to identify as carriers the mothers of boys with SCID or hypogammaglobulinaemia whose phenotype suggested X-linkage and to infer X-linkage in boys with SCID or hypogammaglobulinaemia whose disease was not clearly X-linked on the basis either of family history or clinical and immunological characteristics ."}409{"id": "408", "text": "METHODOLOGY : A polymerase chain reaction-based method was used to amplify a polymorphic CAG repeat in the first exon of the androgen receptor gene after selective digestion of the active X chromosome with a methylation-sensitive enzyme , HpaII to distinguish between the paternal and maternal alleles and to identify their methylation status .", "annotated_text": "METHODOLOGY : A polymerase chain reaction-based method was used to amplify a polymorphic <dna>CAG repeat</dna> in the <dna>first exon</dna> of the <dna>androgen receptor gene</dna> after selective digestion of the <dna>active X chromosome</dna> with a <protein>methylation-sensitive enzyme</protein> , <protein>HpaII</protein> to distinguish between the <dna>paternal and maternal alleles</dna> and to identify their methylation status ."}410{"id": "409", "text": "RESULTS : Heterozygosity was found in 24 of 31 female subjects ( 77 % ) .", "annotated_text": "RESULTS : Heterozygosity was found in 24 of 31 female subjects ( 77 % ) ."}411{"id": "410", "text": "As anticipated , NRXI could be demonstrated in all lymphoid cells studied from obligate carriers of XSCID and an obligate carrier of XLH but not on a carrier of X-linked immunodeficiency with hyper-IgM .", "annotated_text": "As anticipated , NRXI could be demonstrated in all <cell_type>lymphoid cells</cell_type> studied from obligate carriers of XSCID and an obligate carrier of XLH but not on a carrier of X-linked immunodeficiency with <protein>hyper-IgM</protein> ."}412{"id": "411", "text": "The finding of NRXI in the mother of a boy with a SCID variant showed her to be a carrier of XSCID and establishes that her son has XSCID , not otherwise evident from available data .", "annotated_text": "The finding of NRXI in the mother of a boy with a SCID variant showed her to be a carrier of XSCID and establishes that her son has XSCID , not otherwise evident from available data ."}413{"id": "412", "text": "CONCLUSIONS : This PCR assay provides a rapid method for carrier detection of X-linked immunodeficiencies , and has allowed us to expand the phenotype of XSCID", "annotated_text": "CONCLUSIONS : This PCR assay provides a rapid method for carrier detection of X-linked immunodeficiencies , and has allowed us to expand the phenotype of XSCID"}414{"id": "413", "text": "Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-kB-dependent fashion .", "annotated_text": "Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-kB-dependent fashion ."}415{"id": "414", "text": "We addressed the role of hyperglycemia in leukocyte-endothelium interaction under flow conditions by exposing human umbilical vein endothelial cells for 24 h to normal ( 5 mM ) , high concentration of glucose ( 30 mM ) , advanced glycosylation end product-albumin ( 100 microg/ml ) , or hyperglycemic ( 174-316 mg/dl ) sera from patients with diabetes and abnormal hemoglobin A1c ( 8.1+/-1.4 % ) .", "annotated_text": "We addressed the role of hyperglycemia in leukocyte-endothelium interaction under flow conditions by exposing <cell_type>human umbilical vein endothelial cells</cell_type> for 24 h to normal ( 5 mM ) , high concentration of glucose ( 30 mM ) , advanced glycosylation end <protein>product-albumin</protein> ( 100 microg/ml ) , or hyperglycemic ( 174-316 mg/dl ) sera from patients with diabetes and abnormal hemoglobin A1c ( 8.1+/-1.4 % ) ."}416{"id": "415", "text": "At the end of incubation endothelial cells were perfused with total leukocyte suspension in a parallel plate flow chamber under laminar flow ( 1.5 dyn/cm2 ) .", "annotated_text": "At the end of incubation <cell_type>endothelial cells</cell_type> were perfused with total leukocyte suspension in a parallel plate flow chamber under laminar flow ( 1.5 dyn/cm2 ) ."}417{"id": "416", "text": "Rolling and adherent cells were evaluated by digital image processing .", "annotated_text": "Rolling and <cell_type>adherent cells</cell_type> were evaluated by digital image processing ."}418{"id": "417", "text": "Results showed that 30 mM glucose significantly ( P < 0.01 ) increased the number of adherent leukocytes to endothelial cells in respect to control ( 5 mM glucose ; 151+/-19 versus 33+/-8 cells/mm2 ) .", "annotated_text": "Results showed that 30 mM glucose significantly ( P < 0.01 ) increased the number of <cell_type>adherent leukocytes</cell_type> to <cell_type>endothelial cells</cell_type> in respect to control ( 5 mM glucose ; 151+/-19 versus 33+/-8 cells/mm2 ) ."}419{"id": "418", "text": "A similar response was induced by endothelial stimulation with IL-1beta , here used as positive control ( 195+/-20 cells/mm2 ) .", "annotated_text": "A similar response was induced by endothelial stimulation with <protein>IL-1beta</protein> , here used as positive control ( 195+/-20 cells/mm2 ) ."}420{"id": "419", "text": "The number of rolling cells on endothelial surface was not affected by high glucose level .", "annotated_text": "The number of <cell_type>rolling cells</cell_type> on endothelial surface was not affected by high glucose level ."}421{"id": "420", "text": "Stable adhesion of leukocytes to glucose-treated as well as to IL-1beta-stimulated endothelial cells was preceded by short interaction of leukocytes with the endothelial surface .", "annotated_text": "Stable adhesion of <cell_type>leukocytes</cell_type> to glucose-treated as well as to <cell_type>IL-1beta-stimulated endothelial cells</cell_type> was preceded by short interaction of <cell_type>leukocytes</cell_type> with the endothelial surface ."}422{"id": "421", "text": "The distance travelled by leukocytes before arrest on 30 mM glucose , or on IL-1beta-treated endothelial cells , was significantly ( P < 0.01 ) higher than that observed for leukocytes adhering on control endothelium ( 30 mM glucose : 76.7+/-3.5 ; IL1beta : 69.7+/-4 versus 5 mM glucose : 21.5+/-5 microm ) .", "annotated_text": "The distance travelled by <cell_type>leukocytes</cell_type> before arrest on 30 mM glucose , or on <cell_type>IL-1beta-treated endothelial cells</cell_type> , was significantly ( P < 0.01 ) higher than that observed for <cell_type>leukocytes</cell_type> adhering on control endothelium ( 30 mM glucose : 76.7+/-3.5 ; IL1beta : 69.7+/-4 versus 5 mM glucose : 21.5+/-5 microm ) ."}423{"id": "422", "text": "Functional blocking of E-selectin , intercellular cell adhesion molecule-1 , and vascular cell adhesion molecule-1 on endothelial cells with the corresponding mouse mAb significantly inhibited glucose-induced increase in leukocyte adhesion ( 67+/-16 , 83+/-12 , 62+/-8 versus 144+/-21 cells/ mm2 ) .", "annotated_text": "Functional blocking of <protein>E-selectin</protein> , <protein>intercellular cell adhesion molecule-1</protein> , and <protein>vascular cell adhesion molecule-1</protein> on <cell_type>endothelial cells</cell_type> with the corresponding <protein>mouse mAb</protein> significantly inhibited glucose-induced increase in leukocyte adhesion ( 67+/-16 , 83+/-12 , 62+/-8 versus 144+/-21 cells/ mm2 ) ."}424{"id": "423", "text": "Confocal fluorescence microscopy studies showed that 30 mM glucose induced an increase in endothelial surface expression of E-selectin , intercellular cell adhesion molecule-1 , and vascular cell adhesion molecule-1 .", "annotated_text": "Confocal fluorescence microscopy studies showed that 30 mM glucose induced an increase in endothelial surface expression of <protein>E-selectin</protein> , <protein>intercellular cell adhesion molecule-1</protein> , and <protein>vascular cell adhesion molecule-1</protein> ."}425{"id": "424", "text": "Electrophoretic mobility shift assay of nuclear extracts of human umbilical vein endothelial cells ( HUVEC ) exposed for 1 h to 30 mM glucose revealed an intense NF-kB activation .", "annotated_text": "Electrophoretic mobility shift assay of nuclear extracts of <cell_type>human umbilical vein endothelial cells</cell_type> ( HUVEC ) exposed for 1 h to 30 mM glucose revealed an intense <protein>NF-kB</protein> activation ."}426{"id": "425", "text": "Treatment of HUVEC exposed to high glucose with the NF-kB inhibitors pyrrolidinedithiocarbamate ( 100 microM ) and tosyl-phe-chloromethylketone ( 25 microM ) significantly reduced ( P < 0.05 ) leukocyte adhesion in respect to HUVEC treated with glucose alone .", "annotated_text": "Treatment of HUVEC exposed to high glucose with the <protein>NF-kB inhibitors</protein> pyrrolidinedithiocarbamate ( 100 microM ) and tosyl-phe-chloromethylketone ( 25 microM ) significantly reduced ( P < 0.05 ) leukocyte adhesion in respect to HUVEC treated with glucose alone ."}427{"id": "426", "text": "A significant ( P < 0.01 ) inhibitory effect on glucose-induced leukocyte adhesion was observed after blocking protein kinase C activity with staurosporine ( 5 nM ) .", "annotated_text": "A significant ( P < 0.01 ) inhibitory effect on glucose-induced leukocyte adhesion was observed after blocking <protein>protein kinase C</protein> activity with staurosporine ( 5 nM ) ."}428{"id": "427", "text": "When HUVEC were treated with specific antisense oligodesoxynucleotides against PKCalpha and PKCepsilon isoforms before the addition of 30 mM glucose , a significant ( P < 0.05 ) reduction in the adhesion was also seen .", "annotated_text": "When HUVEC were treated with specific antisense oligodesoxynucleotides against <protein>PKCalpha and PKCepsilon isoforms</protein> before the addition of 30 mM glucose , a significant ( P < 0.05 ) reduction in the adhesion was also seen ."}429{"id": "428", "text": "Advanced glycosylation end product-albumin significantly increased the number of adhering leukocytes in respect to native albumin used as control ( 110+/-16 versus 66+/-7 , P < 0.01 ) .", "annotated_text": "Advanced glycosylation end <protein>product-albumin</protein> significantly increased the number of <cell_type>adhering leukocytes</cell_type> in respect to <protein>native albumin</protein> used as control ( 110+/-16 versus 66+/-7 , P < 0.01 ) ."}430{"id": "429", "text": "Sera from diabetic patients significantly ( P < 0.01 ) enhanced leukocyte adhesion as compared with controls , despite normal levels of IL-1beta and TNFalpha in these sera .", "annotated_text": "Sera from diabetic patients significantly ( P < 0.01 ) enhanced leukocyte adhesion as compared with controls , despite normal levels of <protein>IL-1beta</protein> and <protein>TNFalpha</protein> in these sera ."}431{"id": "430", "text": "These data indicate that high glucose concentration and hyperglycemia promote leukocyte adhesion to the endothelium through upregulation of cell surface expression of adhesive proteins , possibly depending on NF-kB activation .", "annotated_text": "These data indicate that high glucose concentration and hyperglycemia promote leukocyte adhesion to the endothelium through upregulation of cell surface expression of adhesive proteins , possibly depending on <protein>NF-kB</protein> activation ."}432{"id": "431", "text": "Ikaros in hemopoietic lineage determination and homeostasis .", "annotated_text": "<protein>Ikaros</protein> in hemopoietic lineage determination and homeostasis ."}433{"id": "432", "text": "Studies on the molecular mechanisms that control hemopoietic differentiation have focused on signaling cascades and nuclear effectors that drive this complex developmental system in a regulated fashion .", "annotated_text": "Studies on the molecular mechanisms that control hemopoietic differentiation have focused on signaling cascades and nuclear effectors that drive this complex developmental system in a regulated fashion ."}434{"id": "433", "text": "Here we review the role of Ikaros , the founding member of a unique family of zinc finger transcription factors in this developmental process .", "annotated_text": "Here we review the role of <protein>Ikaros</protein> , the founding member of a unique family of <protein>zinc finger transcription factors</protein> in this developmental process ."}435{"id": "434", "text": "Studies on an Ikaros null mutation have revealed an essential role for this factor in lymphoid cell fate determination and at subsequent branch points of the T cell differentiation pathway .", "annotated_text": "Studies on an <protein>Ikaros</protein> null mutation have revealed an essential role for this factor in lymphoid cell fate determination and at subsequent branch points of the T cell differentiation pathway ."}436{"id": "435", "text": "Differences in the phenotypes of a null and a dominant negative ( DN ) Ikaros mutation provide insight into a regulatory network through which Ikaros proteins exert their effects in development .", "annotated_text": "Differences in the phenotypes of a null and a <dna>dominant negative ( DN ) Ikaros mutation</dna> provide insight into a regulatory network through which <protein>Ikaros proteins</protein> exert their effects in development ."}437{"id": "436", "text": "In addition a comparative analysis of the hemopoietic stem cell and precursor compartment resulting from the two Ikaros mutations reveals a profound yet not absolute requirement for Ikaros", "annotated_text": "In addition a comparative analysis of the <cell_type>hemopoietic stem cell</cell_type> and precursor compartment resulting from the two <dna>Ikaros mutations</dna> reveals a profound yet not absolute requirement for <protein>Ikaros</protein>"}438{"id": "437", "text": "Induction of early B cell factor ( EBF ) and multiple B lineage genes by the basic helix-loop-helix transcription factor E12 .", "annotated_text": "Induction of <protein>early B cell factor</protein> ( <protein>EBF</protein> ) and <dna>multiple B lineage genes</dna> by the <protein>basic helix-loop-helix transcription factor</protein> <protein>E12</protein> ."}439{"id": "438", "text": "The transcription factors encoded by the E2A and early B cell factor ( EBF ) genes are required for the proper development of B lymphocytes .", "annotated_text": "The <protein>transcription factors</protein> encoded by the <protein>E2A</protein> and <protein>early B cell factor</protein> ( <protein>EBF</protein> ) genes are required for the proper development of <cell_type>B lymphocytes</cell_type> ."}440{"id": "439", "text": "However , the absence of B lineage cells in E2A- and EBF-deficient mice has made it difficult to determine the function or relationship between these proteins .", "annotated_text": "However , the absence of <cell_type>B lineage cells</cell_type> in E2A- and EBF-deficient mice has made it difficult to determine the function or relationship between these proteins ."}441{"id": "440", "text": "We report the identification of a novel model system in which the role of E2A and EBF in the regulation of multiple B lineage traits can be studied .", "annotated_text": "We report the identification of a novel model system in which the role of <protein>E2A</protein> and <protein>EBF</protein> in the regulation of multiple B lineage traits can be studied ."}442{"id": "441", "text": "We found that the conversion of 70Z/3 pre-B lymphocytes to cells with a macrophage-like phenotype is associated with the loss of E2A and EBF .", "annotated_text": "We found that the conversion of <cell_line>70Z/3 pre-B lymphocytes</cell_line> to cells with a macrophage-like phenotype is associated with the loss of <protein>E2A</protein> and <protein>EBF</protein> ."}443{"id": "442", "text": "Moreover , we show that ectopic expression of the E2A protein E12 in this macrophage line results in the induction of many B lineage genes , including EBF , IL7Ralpha , lambda5 , and Rag-1 , and the ability to induce kappa light chain in response to mitogen .", "annotated_text": "Moreover , we show that ectopic expression of the <protein>E2A</protein> protein <protein>E12</protein> in this <cell_line>macrophage line</cell_line> results in the induction of <dna>many B lineage genes</dna> , including <protein>EBF</protein> , <protein>IL7Ralpha</protein> , <protein>lambda5</protein> , and Rag-1 , and the ability to induce <protein>kappa light chain</protein> in response to mitogen ."}444{"id": "443", "text": "Activation of EBF may be one of the critical functions of E12 in regulating the B lineage phenotype since expression of EBF alone leads to the activation of a subset of E12 -inducible traits .", "annotated_text": "Activation of <protein>EBF</protein> may be one of the critical functions of <protein>E12</protein> in regulating the B lineage phenotype since expression of <protein>EBF</protein> alone leads to the activation of a subset of <protein>E12</protein> -inducible traits ."}445{"id": "444", "text": "Our data demonstrate that , in the context of this macrophage line , E12 induces expression of EBF and together these transcription factors coordinately regulate numerous B lineage-associated genes .", "annotated_text": "Our data demonstrate that , in the context of this <cell_line>macrophage line</cell_line> , <protein>E12</protein> induces expression of <protein>EBF</protein> and together these <protein>transcription factors</protein> coordinately regulate numerous <dna>B lineage-associated genes</dna> ."}446{"id": "445", "text": "Activation-induced down-regulation of retinoid receptor RXRalpha expression in human T lymphocytes .", "annotated_text": "Activation-induced down-regulation of <protein>retinoid receptor RXRalpha</protein> expression in <cell_type>human T lymphocytes</cell_type> ."}447{"id": "446", "text": "Role of cell cycle regulation .", "annotated_text": "Role of cell cycle regulation ."}448{"id": "447", "text": "A 5.4-kilobase mRNA , the expression of which is down-regulated after treatment of human peripheral blood mononuclear cells ( PBMCs ) with various T cell-activating agents , was isolated using an mRNA differential display method .", "annotated_text": "A <rna>5.4-kilobase mRNA</rna> , the expression of which is down-regulated after treatment of <cell_type>human peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMCs</cell_type> ) with various T cell-activating agents , was isolated using an mRNA differential display method ."}449{"id": "448", "text": "Nucleotide sequence analysis identified the 5 ' end of this RNA as human retinoid receptor RXRalpha mRNA .", "annotated_text": "Nucleotide sequence analysis identified the <rna>5 ' end</rna> of this <rna>RNA</rna> as <rna>human retinoid receptor RXRalpha mRNA</rna> ."}450{"id": "449", "text": "Here , we report the nucleotide sequence of 3.6 kilobases of this RNA , which represents the 3 ' end of RXRalpha mRNA , the sequence of which has not been previously described .", "annotated_text": "Here , we report the nucleotide sequence of <dna>3.6 kilobases</dna> of this RNA , which represents the <rna>3 ' end</rna> of <rna>RXRalpha mRNA</rna> , the sequence of which has not been previously described ."}451{"id": "450", "text": "Activated PBMCs also expressed lower levels of RXRalpha protein , and a DNA binding assay showed that the activation-induced loss of RXRalpha mRNA and protein expression correlated with the loss of DNA binding activity of this protein .", "annotated_text": "Activated <cell_type>PBMCs</cell_type> also expressed lower levels of <protein>RXRalpha</protein> protein , and a DNA binding assay showed that the activation-induced loss of <rna>RXRalpha mRNA</rna> and protein expression correlated with the loss of DNA binding activity of this protein ."}452{"id": "451", "text": "We present evidence that the transition from G0/G1 to S phase of the cell cycle results in the down-regulation of RXRalpha expression and that cell cycle inhibitors , which block the cells in G1 phase , prevent this down-regulation .", "annotated_text": "We present evidence that the transition from G0/G1 to S phase of the cell cycle results in the down-regulation of <protein>RXRalpha</protein> expression and that cell cycle inhibitors , which block the cells in G1 phase , prevent this down-regulation ."}453{"id": "452", "text": "The decrease in the levels of RXRalpha mRNA was found to be regulated at the post-transcriptional level and involved new protein synthesis .", "annotated_text": "The decrease in the levels of <rna>RXRalpha mRNA</rna> was found to be regulated at the post-transcriptional level and involved new protein synthesis ."}454{"id": "453", "text": "These observations indicate that the levels of RXRalpha expression in T lymphocytes are coupled to cell cycle progression , and there is tight regulatory control of RXRalpha expression during the transition from G0/G1 to S phase of the cell cycle .", "annotated_text": "These observations indicate that the levels of <protein>RXRalpha</protein> expression in T lymphocytes are coupled to cell cycle progression , and there is tight regulatory control of <protein>RXRalpha</protein> expression during the transition from G0/G1 to S phase of the cell cycle ."}455{"id": "454", "text": "Epidemiology and pathogenesis of AIDS-related lymphomas .", "annotated_text": "Epidemiology and pathogenesis of AIDS-related lymphomas ."}456{"id": "455", "text": "Among patients with congenital and acquired immunodeficiencies , non-Hodgkin 's lymphoma ( NHLs ) are the most common tumors of the immune system .", "annotated_text": "Among patients with congenital and acquired immunodeficiencies , non-Hodgkin 's lymphoma ( NHLs ) are the most common tumors of the immune system ."}457{"id": "456", "text": "In the setting of human immunodeficiency virus ( HIV ) infection , as many as 10 % to 20 % of people ultimately developed NHLs .", "annotated_text": "In the setting of human immunodeficiency virus ( HIV ) infection , as many as 10 % to 20 % of people ultimately developed NHLs ."}458{"id": "457", "text": "These tumors are clinically aggressive , frequently involve extranodal sites , and often exhibit unique features that distinguish them from NHL arising in individuals with other forms of immunosuppression .", "annotated_text": "These tumors are clinically aggressive , frequently involve extranodal sites , and often exhibit unique features that distinguish them from NHL arising in individuals with other forms of immunosuppression ."}459{"id": "458", "text": "Important in the development of HIV-associated NHL are cytokines and other factors that induce B-cell proliferation and increase the likelihood of mutations of c-myc , bcl-6 , and other tumor-suppressor genes with carcinogenic potential .", "annotated_text": "Important in the development of HIV-associated NHL are <protein>cytokines</protein> and other factors that induce B-cell proliferation and increase the likelihood of mutations of <dna>c-myc</dna> , <dna>bcl-6</dna> , and other <dna>tumor-suppressor genes</dna> with carcinogenic potential ."}460{"id": "459", "text": "Specific forms of HIV-associated NHL are linked to expression of Epstein-Barr virus ( EBV ) -latent proteins ; the newly described DNA virus , Karposi 's sarcoma-associated herpesvirus/human herpesvirus-8 ( KSHV/HHV-8 ) ; and perhaps HIV .", "annotated_text": "Specific forms of HIV-associated NHL are linked to expression of <protein>Epstein-Barr virus ( EBV ) -latent proteins</protein> ; the newly described DNA virus , Karposi 's sarcoma-associated herpesvirus/human herpesvirus-8 ( KSHV/HHV-8 ) ; and perhaps HIV ."}461{"id": "460", "text": "Elucidation of the factors that contribute to the high incidence of NHL among patients infected with HIV provides insights into important elements of lymphomagenesis .", "annotated_text": "Elucidation of the factors that contribute to the high incidence of NHL among patients infected with HIV provides insights into important elements of lymphomagenesis ."}462{"id": "461", "text": "Matrix metalloproteinase expression in human breast cancer : an immunohistochemical study including correlation with cathepsin D , type IV collagen , laminin , fibronectin , EGFR , c-erbB-2 oncoprotein , p53 , steroid receptors status and proliferative indices .", "annotated_text": "<protein>Matrix metalloproteinase</protein> expression in human breast cancer : an immunohistochemical study including correlation with <protein>cathepsin D</protein> , <protein>type IV collagen</protein> , <protein>laminin</protein> , <protein>fibronectin</protein> , <protein>EGFR</protein> , <protein>c-erbB-2 oncoprotein</protein> , <protein>p53</protein> , steroid receptors status and proliferative indices ."}463{"id": "462", "text": "Matrix metalloproteinase s ( MMPs ) are a group of enzymes thought to be responsible for both normal connective tissue matrix remodelling and accelerated breakdown associated with tumour development .", "annotated_text": "<protein>Matrix metalloproteinase</protein> s ( <protein>MMPs</protein> ) are a group of enzymes thought to be responsible for both normal connective tissue matrix remodelling and accelerated breakdown associated with tumour development ."}464{"id": "463", "text": "The current study aimed to investigate the immunohistochemical expression of matrix metalloproteinase 3 ( MMP-3 , stromelysin-1 ) in correlation with the expression of Basement Membrane ( BM ) antigen ( type IV collagen , laminin ) , fibronectin , cathepsin D , p53 , c-erbB-2 , proliferative activity ( Ki-67 , PCNA ) , steroid receptor content as well as to the other conventional clinicopathological parameters in breast cancer .", "annotated_text": "The current study aimed to investigate the immunohistochemical expression of <protein>matrix metalloproteinase 3</protein> ( <protein>MMP-3</protein> , <protein>stromelysin-1</protein> ) in correlation with the expression of <protein>Basement Membrane ( BM ) antigen</protein> ( <protein>type IV collagen</protein> , <protein>laminin</protein> ) , <protein>fibronectin</protein> , <protein>cathepsin D</protein> , <protein>p53</protein> , <protein>c-erbB-2</protein> , proliferative activity ( <protein>Ki-67</protein> , <protein>PCNA</protein> ) , steroid receptor content as well as to the other conventional clinicopathological parameters in breast cancer ."}465{"id": "464", "text": "This study was performed on a series of frozen and paraffin sections from 84 breast cancer specimens by immunohistochemistry using the monoclonal antibody MMP-3 ( Ab-1 ) .", "annotated_text": "This study was performed on a series of frozen and paraffin sections from 84 breast cancer specimens by immunohistochemistry using the <protein>monoclonal antibody MMP-3</protein> ( <protein>Ab-1</protein> ) ."}466{"id": "465", "text": "Stromelysin-1 ( ST1 ) was observed in about 10 % of epithelial cells in the control groups ( cases of fibrocystic and benign proliferative breast disease ) , while expression ( > 10 % of expression ) was detected in 89.7 % of tumours .", "annotated_text": "<protein>Stromelysin-1</protein> ( <protein>ST1</protein> ) was observed in about 10 % of <cell_type>epithelial cells</cell_type> in the control groups ( cases of fibrocystic and benign proliferative breast disease ) , while expression ( > 10 % of expression ) was detected in 89.7 % of tumours ."}467{"id": "466", "text": "The expression of ST1 in carcinoma cells was strongly associated with its presence in the stroma ( p < 0.001 ) .", "annotated_text": "The expression of <protein>ST1</protein> in carcinoma cells was strongly associated with its presence in the stroma ( p < 0.001 ) ."}468{"id": "467", "text": "A significantly positive correlation was found between ST1 expression , and p53 tumour suppressor gene product ( p = 0.004 ) , and a relationship with c-erbB-2 protein and progesterone receptor status was also indicated .", "annotated_text": "A significantly positive correlation was found between <protein>ST1</protein> expression , and <protein>p53</protein> tumour suppressor gene product ( p = 0.004 ) , and a relationship with <protein>c-erbB-2</protein> protein and progesterone receptor status was also indicated ."}469{"id": "468", "text": "These findings suggest that ST1 expression in breast cancer tissue is irrespective of the expression of the extracellular matrix component , the proteolytic enzyme cathepsin D and the growth fraction of the tumour , and that it could be a potential new prognostic marker in breast cancer .", "annotated_text": "These findings suggest that <protein>ST1</protein> expression in breast cancer tissue is irrespective of the expression of the extracellular matrix component , the <protein>proteolytic enzyme</protein> <protein>cathepsin D</protein> and the growth fraction of the tumour , and that it could be a potential new prognostic marker in breast cancer ."}470{"id": "469", "text": "Use of transfected liver cells to evaluate potential mechanisms of alcohol-induced liver injury [ see comments ]", "annotated_text": "Use of <cell_line>transfected liver cells</cell_line> to evaluate potential mechanisms of alcohol-induced liver injury [ see comments ]"}471{"id": "470", "text": "There is increased activity of the proinflammatory cytokine , tumor necrosis factor ( TNF ) in alcoholic liver disease ( ALD ) .", "annotated_text": "There is increased activity of the <protein>proinflammatory cytokine</protein> , <protein>tumor necrosis factor</protein> ( <protein>TNF</protein> ) in alcoholic liver disease ( ALD ) ."}472{"id": "471", "text": "Hepatic neutrophil infiltration is a principal injurious manifestation of ALD .", "annotated_text": "Hepatic neutrophil infiltration is a principal injurious manifestation of ALD ."}473{"id": "472", "text": "TNF can induce cellular oxidative injury directly , and indirectly by inducing neutrophil chemotactic factor ( IL-8 ) production by hepatocytes .", "annotated_text": "<protein>TNF</protein> can induce cellular oxidative injury directly , and indirectly by inducing neutrophil chemotactic factor ( <protein>IL-8</protein> ) production by hepatocytes ."}474{"id": "473", "text": "IL-8 activates and chemotactically attracts neutrophils to the liver where they release oxidizing substances .", "annotated_text": "<protein>IL-8</protein> activates and chemotactically attracts neutrophils to the liver where they release oxidizing substances ."}475{"id": "474", "text": "Patients with ALD also have decreased protective factors for cellular oxidative injury .", "annotated_text": "Patients with ALD also have decreased <protein>protective factors</protein> for cellular oxidative injury ."}476{"id": "475", "text": "Manganous superoxide dismutase ( MnSOD ) is an antioxidant protective factor .", "annotated_text": "<protein>Manganous superoxide dismutase</protein> ( <protein>MnSOD</protein> ) is an <protein>antioxidant protective factor</protein> ."}477{"id": "476", "text": "The objectives of these studies were to investigate mechanisms for induction of an injurious factor ( IL-8 ) and a protective factor ( MnSOD ) in the HepG2 human hepatoma cell line .", "annotated_text": "The objectives of these studies were to investigate mechanisms for induction of an <protein>injurious factor</protein> ( <protein>IL-8</protein> ) and a <protein>protective factor</protein> ( <protein>MnSOD</protein> ) in the <cell_line>HepG2 human hepatoma cell line</cell_line> ."}478{"id": "477", "text": "In the first set of experiments , IL-8 gene reporter constructs were used to transiently transfect a derivative ( MVh2E1-9 ) of the HepG2 cell line which expresses P-4502E1 and metabolizes ethanol .", "annotated_text": "In the first set of experiments , <dna>IL-8 gene reporter constructs</dna> were used to transiently transfect a derivative ( <cell_line>MVh2E1-9</cell_line> ) of the <cell_line>HepG2 cell line</cell_line> which expresses <protein>P-4502E1</protein> and metabolizes ethanol ."}479{"id": "478", "text": "Inactivation of the NF-kappaB and 3'NF-IL-6 DNA binding sites decreased IL-8 gene transcriptional activation in response to TNF while inactivation of the 5'NF-IL-6 binding site increased IL-8 gene transcriptional activity in response to TNF .", "annotated_text": "Inactivation of the <dna>NF-kappaB and 3'NF-IL-6 DNA binding sites</dna> decreased <dna>IL-8 gene</dna> transcriptional activation in response to <protein>TNF</protein> while inactivation of the <dna>5'NF-IL-6 binding site</dna> increased <dna>IL-8 gene</dna> transcriptional activity in response to <protein>TNF</protein> ."}480{"id": "479", "text": "This system may be useful to assess the effects of ethanol on TNF -induced hepatocyte IL-8 production .", "annotated_text": "This system may be useful to assess the effects of ethanol on <protein>TNF</protein> -induced hepatocyte <protein>IL-8</protein> production ."}481{"id": "480", "text": "In the second set of experiments , HepG2 cells were cultured in 25 to 100 mmol concentrations of ethanol .", "annotated_text": "In the second set of experiments , <cell_line>HepG2 cells</cell_line> were cultured in 25 to 100 mmol concentrations of ethanol ."}482{"id": "481", "text": "Both TNF and ethanol increased HepG2 cell MnSOD activity in short-term ( 72 hr ) cultures with ethanol .", "annotated_text": "Both <protein>TNF</protein> and ethanol increased <cell_line>HepG2 cell</cell_line> <protein>MnSOD</protein> activity in short-term ( 72 hr ) cultures with ethanol ."}483{"id": "482", "text": "However , after long-term ( 10 weeks ) culture with ethanol , there was no induction of MnSOD by ethanol and there was a diminished induction of MnSOD in response to TNF .", "annotated_text": "However , after long-term ( 10 weeks ) culture with ethanol , there was no induction of <protein>MnSOD</protein> by ethanol and there was a diminished induction of <protein>MnSOD</protein> in response to <protein>TNF</protein> ."}484{"id": "483", "text": "Further studies are needed to assess the effect of this diminished induction of MnSOD with chronic ethanol culture on HepG2 cell susceptibility to TNF cytotoxicity .", "annotated_text": "Further studies are needed to assess the effect of this diminished induction of <protein>MnSOD</protein> with chronic ethanol culture on <cell_line>HepG2 cell</cell_line> susceptibility to <cell_line>TNF cytotoxicity</cell_line> ."}485{"id": "484", "text": "We conclude that transfected liver cell lines can be used to evaluate mechanisms for increased injurious factors and decreased protective factors in alcoholic liver injury .", "annotated_text": "We conclude that transfected <cell_line>liver cell lines</cell_line> can be used to evaluate mechanisms for increased <protein>injurious factors</protein> and decreased <protein>protective factors</protein> in alcoholic liver injury ."}486{"id": "485", "text": "Tissue factor transcription driven by Egr-1 is a critical mechanism of murine pulmonary fibrin deposition in hypoxia .", "annotated_text": "Tissue factor transcription driven by <protein>Egr-1</protein> is a critical mechanism of <protein>murine pulmonary fibrin</protein> deposition in hypoxia ."}487{"id": "486", "text": "Local hypoxemia and stasis trigger thrombosis .", "annotated_text": "Local hypoxemia and stasis trigger thrombosis ."}488{"id": "487", "text": "We have demonstrated previously that in a murine model of normobaric hypoxia pulmonary fibrin deposition is a result of expression of tissue factor , especially in oxygen-deprived mononuclear phagocytes ( MPs ) .", "annotated_text": "We have demonstrated previously that in a murine model of normobaric hypoxia pulmonary <protein>fibrin</protein> deposition is a result of expression of <protein>tissue factor</protein> , especially in <protein>oxygen-deprived mononuclear phagocytes</protein> ( <protein>MPs</protein> ) ."}489{"id": "488", "text": "We now show that transcription factor early-growth-response gene product ( Egr-1 ) is rapidly activated in hypoxia , both in vitro and in vivo , and is responsible for transcription and expression of tissue factor in hypoxic lung .", "annotated_text": "We now show that <protein>transcription factor early-growth-response gene product</protein> ( <protein>Egr-1</protein> ) is rapidly activated in hypoxia , both in vitro and in vivo , and is responsible for transcription and expression of <protein>tissue factor</protein> in hypoxic lung ."}490{"id": "489", "text": "MPs and HeLa cells subjected to hypoxia ( pO2 approximately 13 torr ) had increased levels of tissue factor transcripts ( approximately 18-fold ) and an increased rate of transcription ( approximately 15-fold ) , based on nuclear run-on analysis .", "annotated_text": "<protein>MPs</protein> and <cell_line>HeLa cells</cell_line> subjected to hypoxia ( pO2 approximately 13 torr ) had increased levels of <rna>tissue factor transcripts</rna> ( approximately 18-fold ) and an increased rate of transcription ( approximately 15-fold ) , based on nuclear run-on analysis ."}491{"id": "490", "text": "Gel-shift analysis of nuclear extracts from hypoxic MPs and HeLa cells demonstrated increased DNA-binding activity at the serum response region ( SRR ; -111/+14 bp ) of the tissue factor promoter at Egr-1 motifs .", "annotated_text": "Gel-shift analysis of nuclear extracts from <protein>hypoxic MPs</protein> and <cell_line>HeLa cells</cell_line> demonstrated increased DNA-binding activity at the <dna>serum response region</dna> ( SRR ; -111/+14 bp ) of the <dna>tissue factor promoter</dna> at <dna>Egr-1 motifs</dna> ."}492{"id": "491", "text": "Using 32P-labeled Egr consensus oligonucleotide , we observed induction of DNA-binding activity in nuclear extracts from hypoxic lung and HeLa cells because of activation of Egr-1 , by means of supershift analysis .", "annotated_text": "Using 32P-labeled Egr consensus oligonucleotide , we observed induction of DNA-binding activity in nuclear extracts from hypoxic lung and <cell_line>HeLa cells</cell_line> because of activation of <protein>Egr-1</protein> , by means of supershift analysis ."}493{"id": "492", "text": "Transient transfection of HeLa cells with chimeric plasmids containing wild-type or mutant SRR from the tissue factor promoter showed that intact Sp1 sites are necessary for basal promoter activity , whereas the integrity of Egr-1 sites was required for hypoxia-enhanced expression .", "annotated_text": "Transient transfection of <cell_line>HeLa cells</cell_line> with <dna>chimeric plasmids</dna> containing <protein>wild-type or mutant SRR</protein> from the <dna>tissue factor promoter</dna> showed that <dna>intact Sp1 sites</dna> are necessary for basal promoter activity , whereas the integrity of <dna>Egr-1 sites</dna> was required for hypoxia-enhanced expression ."}494{"id": "493", "text": "A central role for Egr-1 in hypoxia-mediated tissue factor expression was confirmed by experiments with homozygous Egr-1 null mice ; wild-type mice subjected to oxygen deprivation expressed tissue factor and showed fibrin deposition , but hypoxic homozygous Egr-1 null mice displayed neither tissue factor nor fibrin .", "annotated_text": "A central role for <protein>Egr-1</protein> in hypoxia-mediated tissue factor expression was confirmed by experiments with homozygous <protein>Egr-1</protein> null mice ; wild-type mice subjected to <protein>oxygen deprivation expressed tissue factor</protein> and showed <protein>fibrin</protein> deposition , but hypoxic homozygous <protein>Egr-1</protein> null mice displayed neither <protein>tissue factor</protein> nor <protein>fibrin</protein> ."}495{"id": "494", "text": "These data delineate a novel biology for hypoxia-induced fibrin deposition , in which oxygen deprivation-induced activation of Egr-1 , resulting in expression of tissue factor , has an unexpected and central role .", "annotated_text": "These data delineate a novel biology for hypoxia-induced <protein>fibrin</protein> deposition , in which oxygen deprivation-induced activation of <protein>Egr-1</protein> , resulting in expression of <protein>tissue factor</protein> , has an unexpected and central role ."}496{"id": "495", "text": "Kinetics of cytokine and NFAT gene expression in human interleukin-2-dependent T lymphoblasts stimulated via T-cell receptor .", "annotated_text": "Kinetics of cytokine and NFAT gene expression in <cell_line>human interleukin-2-dependent T lymphoblasts</cell_line> stimulated via <protein>T-cell receptor</protein> ."}497{"id": "496", "text": "T cells respond to mitogenic or antigenic stimulation by proliferation and by turning on cytokine gene expression .", "annotated_text": "<cell_type>T cells</cell_type> respond to mitogenic or antigenic stimulation by proliferation and by turning on cytokine gene expression ."}498{"id": "497", "text": "Here we have analysed the kinetics and nature of cytokine production in human peripheral blood-derived T lymphoblasts stimulated with anti-CD3 antibodies or Lens culinaris lectin ( LCL ) .", "annotated_text": "Here we have analysed the kinetics and nature of cytokine production in <cell_type>human peripheral blood-derived T lymphoblasts</cell_type> stimulated with <protein>anti-CD3 antibodies</protein> or <protein>Lens culinaris lectin</protein> ( <protein>LCL</protein> ) ."}499{"id": "498", "text": "T cells were purified from peripheral blood mononuclear cells ( PBMC ) and primarily activated with anti-CD3 antibodies and cultured in the presence of interleukin-2 ( IL-2 ) .", "annotated_text": "<cell_type>T cells</cell_type> were purified from <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) and primarily activated with <protein>anti-CD3 antibodies</protein> and cultured in the presence of <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) ."}500{"id": "499", "text": "Anti-CD3-restimulated T cells ( mainly CD8+ ) produced IL-2 , interferon-gamma ( IFN-gamma ) and tumour necrosis factor-alpha ( TNF-alpha ) and low levels of IL-4 and IL-10 transcripts and proteins .", "annotated_text": "Anti-CD3-restimulated <cell_type>T cells</cell_type> ( mainly CD8+ ) produced <protein>IL-2</protein> , <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) and <protein>tumour necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) and low levels of <rna>IL-4 and IL-10 transcripts</rna> and proteins ."}501{"id": "500", "text": "No IL-6 gene expression was observed .", "annotated_text": "No <dna>IL-6 gene</dna> expression was observed ."}502{"id": "501", "text": "In LCL-stimulated cells the cytokine production pattern was very similar .", "annotated_text": "In <cell_type>LCL-stimulated cells</cell_type> the cytokine production pattern was very similar ."}503{"id": "502", "text": "Steady-state mRNA levels of IL-2 , IL-10 and IFN-gamma peaked at 3 hr after anti-CD3 stimulation and declined rapidly thereafter .", "annotated_text": "Steady-state mRNA levels of <protein>IL-2</protein> , <protein>IL-10</protein> and <protein>IFN-gamma</protein> peaked at 3 hr after anti-CD3 stimulation and declined rapidly thereafter ."}504{"id": "503", "text": "The kinetics of TNF-alpha mRNA expression was faster , being at its peak level 1 hr after stimulation .", "annotated_text": "The kinetics of <rna>TNF-alpha mRNA</rna> expression was faster , being at its peak level 1 hr after stimulation ."}505{"id": "504", "text": "Anti-CD3-stimulated IL-2 gene expression was down-regulated by protein synthesis inhibitor , whereas IL-10 , IFN-gamma and TNF-alpha genes were readily induced independent of ongoing protein synthesis .", "annotated_text": "Anti-CD3-stimulated <dna>IL-2 gene</dna> expression was down-regulated by protein synthesis inhibitor , whereas <dna>IL-10 , IFN-gamma and TNF-alpha genes</dna> were readily induced independent of ongoing protein synthesis ."}506{"id": "505", "text": "T-cell receptor stimulation also induced a very rapid expression of c-jun , c-fos and NFATc1 ( NFATc ) genes , the gene products of which are involved in cytokine gene expression .", "annotated_text": "<protein>T-cell receptor</protein> stimulation also induced a very rapid expression of <dna>c-jun , c-fos and NFATc1 ( NFATc ) genes</dna> , the gene products of which are involved in cytokine gene expression ."}507{"id": "506", "text": "In conclusion , the cytokines synthesized by IL-2-dependent T cells were predominantly IL-2 , IFN-gamma and TNF-alpha .", "annotated_text": "In conclusion , the <protein>cytokines</protein> synthesized by <cell_type>IL-2-dependent T cells</cell_type> were predominantly <protein>IL-2</protein> , <protein>IFN-gamma</protein> and <protein>TNF-alpha</protein> ."}508{"id": "507", "text": "An animal model to study local oxidation of LDL and its biological effects in the arterial wall .", "annotated_text": "An animal model to study local oxidation of LDL and its biological effects in the arterial wall ."}509{"id": "508", "text": "Oxidized LDL ( oxLDL ) is present in atherosclerotic lesions and is believed to play a key role in atherogenesis .", "annotated_text": "Oxidized LDL ( oxLDL ) is present in atherosclerotic lesions and is believed to play a key role in atherogenesis ."}510{"id": "509", "text": "Mainly on the basis of cell culture studies , oxLDL has been shown to produce many biological effects that influence the atherosclerotic process .", "annotated_text": "Mainly on the basis of cell culture studies , oxLDL has been shown to produce many biological effects that influence the atherosclerotic process ."}511{"id": "510", "text": "To study LDL oxidation in vivo , we have established a model in which Sprague-Dawley rats are given a single injection of unmodified human LDL ( > or = 4 mg/kg body weight ) .", "annotated_text": "To study LDL oxidation in vivo , we have established a model in which Sprague-Dawley rats are given a single injection of unmodified human LDL ( > or = 4 mg/kg body weight ) ."}512{"id": "511", "text": "Within 6 hours , an accumulation of apolipoprotein B and epitopes present on oxLDL are detected in the arterial endothelium and media .", "annotated_text": "Within 6 hours , an accumulation of apolipoprotein B and <protein>epitopes</protein> present on oxLDL are detected in the arterial endothelium and media ."}513{"id": "512", "text": "The presence of oxLDL is associated with activation of the transcription factor nuclear factor-kappaB in the endothelium as well as endothelial expression of intercellular adhesion molecule-1 .", "annotated_text": "The presence of oxLDL is associated with activation of the <protein>transcription factor</protein> <protein>nuclear factor-kappaB</protein> in the endothelium as well as endothelial expression of <protein>intercellular adhesion molecule-1</protein> ."}514{"id": "513", "text": "Injection of LDL enriched with the antioxidant probucol resulted in arterial accumulation of apolipoprotein B , but the expression of oxLDL-specific epitopes was reduced at 24 hours .", "annotated_text": "Injection of LDL enriched with the antioxidant probucol resulted in arterial accumulation of apolipoprotein B , but the expression of oxLDL-specific epitopes was reduced at 24 hours ."}515{"id": "514", "text": "Thus , this simple model has the potential to analyze the mechanisms behind and biological effects of LDL oxidation in vivo .", "annotated_text": "Thus , this simple model has the potential to analyze the mechanisms behind and biological effects of LDL oxidation in vivo ."}516{"id": "515", "text": "Molecular mechanisms of promoter regulation of the gp34 gene that is trans-activated by an oncoprotein Tax of human T cell leukemia virus type I .", "annotated_text": "Molecular mechanisms of promoter regulation of the <dna>gp34 gene</dna> that is trans-activated by an <protein>oncoprotein Tax</protein> of human T cell leukemia virus type I ."}517{"id": "516", "text": "We investigated the molecular mechanism of transcriptional activation of the gp34 gene by the Tax oncoprotein of human T cell leukemia virus type I ( HTLV-I ) .", "annotated_text": "We investigated the molecular mechanism of transcriptional activation of the <dna>gp34 gene</dna> by the <protein>Tax oncoprotein</protein> of human T cell leukemia virus type I ( HTLV-I ) ."}518{"id": "517", "text": "gp34 is a type II transmembrane molecule belonging to the tumor necrosis factor family and is constitutively expressed on HTLV-I-producing cells but not normal resting T cells .", "annotated_text": "<protein>gp34</protein> is a <protein>type II transmembrane molecule</protein> belonging to the tumor necrosis factor family and is constitutively expressed on <cell_type>HTLV-I-producing cells</cell_type> but not <cell_type>normal resting T cells</cell_type> ."}519{"id": "518", "text": "The transcriptional regulatory region of the gp34 gene was activated by HTLV-I Tax in the human T cell line Jurkat , in which endogenous gp34 is induced by Tax .", "annotated_text": "The transcriptional regulatory region of the <dna>gp34 gene</dna> was activated by HTLV-I <protein>Tax</protein> in the <cell_line>human T cell line Jurkat</cell_line> , in which endogenous <protein>gp34</protein> is induced by <protein>Tax</protein> ."}520{"id": "519", "text": "Sequence analysis demonstrated that two NF-kappaB-like elements ( 1 and 2 ) were present in the regulatory region .", "annotated_text": "Sequence analysis demonstrated that two <dna>NF-kappaB-like elements</dna> ( 1 and 2 ) were present in the <dna>regulatory region</dna> ."}521{"id": "520", "text": "Both NF-kappaB-like elements were able to bind to NF-kappaB or its related factor ( s ) in a Tax -dependent manner .", "annotated_text": "Both <dna>NF-kappaB-like elements</dna> were able to bind to <protein>NF-kappaB</protein> or its related factor ( s ) in a <protein>Tax</protein> -dependent manner ."}522{"id": "521", "text": "Chloramphenicol acetyltransferase assays indicated that NF-kappaB-like element 1 was Tax -responsive , although the activity was lower than that the native promoter .", "annotated_text": "<protein>Chloramphenicol acetyltransferase</protein> assays indicated that <dna>NF-kappaB-like element 1</dna> was <protein>Tax</protein> -responsive , although the activity was lower than that the <dna>native promoter</dna> ."}523{"id": "522", "text": "NF-kappaB -like element 2 elevated promoter activity when combined with NF-kappaB-like element 1 , indicating cooperative function of the elements for maximum promoter function .", "annotated_text": "<protein>NF-kappaB</protein> -like element 2 elevated promoter activity when combined with <dna>NF-kappaB-like element 1</dna> , indicating cooperative function of the elements for maximum promoter function ."}524{"id": "523", "text": "Unlike typical NF-kappaB elements , the NF-kappaB-like elements in gp34 were not activated by treatment of Jurkat cells with phorbol ester despite induction of the NF-kappaB -like binding activity .", "annotated_text": "Unlike typical <dna>NF-kappaB elements</dna> , the <dna>NF-kappaB-like elements</dna> in <protein>gp34</protein> were not activated by treatment of <cell_line>Jurkat cells</cell_line> with phorbol ester despite induction of the <protein>NF-kappaB</protein> -like binding activity ."}525{"id": "524", "text": "Chloramphenicol acetyltransferase reporter assays using the region upstream of the NF-kappaB-like elements identified an upstream region that reduced transcription from cognate and noncognate core promoters in a Tax-independent manner .", "annotated_text": "<protein>Chloramphenicol acetyltransferase</protein> reporter assays using the region upstream of the <dna>NF-kappaB-like elements</dna> identified an upstream region that reduced transcription from <dna>cognate and noncognate core promoters</dna> in a Tax-independent manner ."}526{"id": "525", "text": "Our results imply complex regulation of expression of the gp34 gene and suggest implication of gp34 in proliferation of HTLV-I infected T cells .", "annotated_text": "Our results imply complex regulation of expression of the <dna>gp34 gene</dna> and suggest implication of <protein>gp34</protein> in proliferation of HTLV-I infected T cells ."}527{"id": "526", "text": "beta-Amyloid fibrils activate parallel mitogen-activated protein kinase pathways in microglia and THP1 monocytes .", "annotated_text": "<protein>beta-Amyloid fibrils</protein> activate parallel <protein>mitogen-activated protein kinase</protein> pathways in <cell_type>microglia</cell_type> and <cell_line>THP1 monocytes</cell_line> ."}528{"id": "527", "text": "The senile plaques of Alzheimer 's disease are foci of local inflammatory responses , as evidenced by the presence of acute phase proteins and oxidative damage .", "annotated_text": "The senile plaques of Alzheimer 's disease are foci of local inflammatory responses , as evidenced by the presence of <protein>acute phase proteins</protein> and oxidative damage ."}529{"id": "528", "text": "Fibrillar forms of beta-amyloid ( Abeta ) , which are the primary constituents of senile plaques , have been shown to activate tyrosine kinase-dependent signal transduction cascades , resulting in inflammatory responses in microglia .", "annotated_text": "<protein>Fibrillar forms</protein> of <protein>beta-amyloid</protein> ( <protein>Abeta</protein> ) , which are the primary constituents of senile plaques , have been shown to activate tyrosine kinase-dependent signal transduction cascades , resulting in inflammatory responses in <cell_type>microglia</cell_type> ."}530{"id": "529", "text": "However , the downstream signaling pathways mediating Abeta -induced inflammatory events are not well characterized .", "annotated_text": "However , the downstream signaling pathways mediating <protein>Abeta</protein> -induced inflammatory events are not well characterized ."}531{"id": "530", "text": "We report that exposure of primary rat microglia and human THP1 monocytes to fibrillar Abeta results in the tyrosine kinase -dependent activation of two parallel signal transduction cascades involving members of the mitogen-activated protein kinase ( MAPK ) superfamily .", "annotated_text": "We report that exposure of <cell_type>primary rat microglia</cell_type> and <cell_line>human THP1 monocytes</cell_line> to <protein>fibrillar Abeta</protein> results in the <protein>tyrosine kinase</protein> -dependent activation of two parallel signal transduction cascades involving members of the <protein>mitogen-activated protein kinase ( MAPK ) superfamily</protein> ."}532{"id": "531", "text": "Abeta stimulated the rapid , transient activation of extracellular signal-regulated kinase 1 ( ERK1 ) and ERK2 in microglia and ERK2 in THP1 monocytes .", "annotated_text": "<protein>Abeta</protein> stimulated the rapid , transient activation of <protein>extracellular signal-regulated kinase 1</protein> ( <protein>ERK1</protein> ) and <protein>ERK2</protein> in <cell_type>microglia</cell_type> and <protein>ERK2</protein> in <cell_line>THP1 monocytes</cell_line> ."}533{"id": "532", "text": "A second superfamily member , p38 MAPK , was also activated with similar kinetics .", "annotated_text": "A second <protein>superfamily member</protein> , <protein>p38 MAPK</protein> , was also activated with similar kinetics ."}534{"id": "533", "text": "Scavenger receptor and receptor for advanced glycated end products ( RAGE ) ligands failed to activate ERK and p38 MAPK in the absence of significant increases in protein tyrosine phosphorylation , demonstrating that scavenger receptors and RAGE are not linked to these pathways .", "annotated_text": "<protein>Scavenger receptor</protein> and <protein>receptor for advanced glycated end products</protein> ( <protein>RAGE</protein> ) ligands failed to activate <protein>ERK</protein> and <protein>p38 MAPK</protein> in the absence of significant increases in protein tyrosine phosphorylation , demonstrating that <protein>scavenger receptors</protein> and <protein>RAGE</protein> are not linked to these pathways ."}535{"id": "534", "text": "Importantly , the stress-activated protein kinases ( SAPKs ) were not significantly activated in response to Abeta .", "annotated_text": "Importantly , the <protein>stress-activated protein kinases</protein> ( <protein>SAPKs</protein> ) were not significantly activated in response to <protein>Abeta</protein> ."}536{"id": "535", "text": "Downstream effectors of the MAPK signal transduction cascades include MAPKAP kinases , such as RSK1 and RSK2 , as well as transcription factors .", "annotated_text": "Downstream effectors of the MAPK signal transduction cascades include <protein>MAPKAP kinases</protein> , such as <protein>RSK1</protein> and <protein>RSK2</protein> , as well as <protein>transcription factors</protein> ."}537{"id": "536", "text": "Exposure of microglia and THP1 monocytes to Abeta resulted in the activation of RSK1 and RSK2 and phosphorylation of cAMP response element-binding protein at Ser133 , providing a mechanism for Abeta -induced changes in gene expression", "annotated_text": "Exposure of <cell_type>microglia</cell_type> and <cell_line>THP1 monocytes</cell_line> to <protein>Abeta</protein> resulted in the activation of <protein>RSK1</protein> and <protein>RSK2</protein> and phosphorylation of <protein>cAMP response element-binding protein</protein> at Ser133 , providing a mechanism for <protein>Abeta</protein> -induced changes in gene expression"}538{"id": "537", "text": "Regulation of cellular retinoic acid binding protein ( CRABP II ) during human monocyte differentiation in vitro .", "annotated_text": "Regulation of <protein>cellular retinoic acid binding protein</protein> ( <protein>CRABP II</protein> ) during <cell_type>human monocyte</cell_type> differentiation in vitro ."}539{"id": "538", "text": "Cellular retinoic acid binding proteins ( CRABP ) are low molecular weight proteins whose precise function remains unknown .", "annotated_text": "<protein>Cellular retinoic acid binding proteins</protein> ( <protein>CRABP</protein> ) are <protein>low molecular weight proteins</protein> whose precise function remains unknown ."}540{"id": "539", "text": "They bind retinoids and may thereby modulate the intracellular steady-state concentration of retinoids .", "annotated_text": "They bind retinoids and may thereby modulate the intracellular steady-state concentration of retinoids ."}541{"id": "540", "text": "Whereas CRABP I is ubiquitously expressed , CRABP II is mainly detected in various cell types of the skin .", "annotated_text": "Whereas <protein>CRABP I</protein> is ubiquitously expressed , <protein>CRABP II</protein> is mainly detected in various cell types of the skin ."}542{"id": "541", "text": "By representative difference analysis we found that CRABP II is also strongly expressed in human monocyte-derived macrophages ( MAC ) but not in freshly isolated monocytes ( MO ) .", "annotated_text": "By representative difference analysis we found that <protein>CRABP II</protein> is also strongly expressed in <cell_type>human monocyte-derived macrophages</cell_type> ( <cell_type>MAC</cell_type> ) but not in <cell_type>freshly isolated monocytes</cell_type> ( <cell_type>MO</cell_type> ) ."}543{"id": "542", "text": "The CRABP II mRNA was gradually upregulated during differentiation from MO to MAC in the presence of 2 % serum .", "annotated_text": "The <rna>CRABP II mRNA</rna> was gradually upregulated during differentiation from <cell_type>MO</cell_type> to <cell_type>MAC</cell_type> in the presence of 2 % serum ."}544{"id": "543", "text": "Adherence , which is important for MO differentiation , induced CRABP II expression , but the addition of 10 ( -7 ) M retinoic acid inhibited the upregulation of CRABP II expression during MO/MAC differentiation .", "annotated_text": "Adherence , which is important for <cell_type>MO</cell_type> differentiation , induced <protein>CRABP II</protein> expression , but the addition of 10 ( -7 ) M retinoic acid inhibited the upregulation of <protein>CRABP II</protein> expression during MO/MAC differentiation ."}545{"id": "544", "text": "As MO can differentiate along the classical pathway not only to MAC but also to dendritic cells we analyzed the expression of CRABP II in MO-derived dendritic cells cultured with 10 % FCS , IL-4 , and GM-CSF .", "annotated_text": "As <cell_type>MO</cell_type> can differentiate along the classical pathway not only to <cell_type>MAC</cell_type> but also to dendritic cells we analyzed the expression of <protein>CRABP II</protein> in <cell_type>MO-derived dendritic cells</cell_type> cultured with 10 % <protein>FCS</protein> , <protein>IL-4</protein> , and <protein>GM-CSF</protein> ."}546{"id": "545", "text": "In contrast to MAC , MO-derived dendritic cells showed an extremely low expression of CRABP II .", "annotated_text": "In contrast to <cell_type>MAC</cell_type> , <cell_type>MO-derived dendritic cells</cell_type> showed an extremely low expression of <protein>CRABP II</protein> ."}547{"id": "546", "text": "From these results we conclude ( 1 ) that the availability and the metabolism of retinoids may be different in MAC compared to MO and dendritic cells and ( 2 ) that this may influence differentiation and activation of those cells .", "annotated_text": "From these results we conclude ( 1 ) that the availability and the metabolism of retinoids may be different in <cell_type>MAC</cell_type> compared to <cell_type>MO</cell_type> and <cell_type>dendritic cells</cell_type> and ( 2 ) that this may influence differentiation and activation of those cells ."}548{"id": "547", "text": "Transcription factor B-cell-specific activator protein ( BSAP ) is differentially expressed in B cells and in subsets of B-cell lymphomas .", "annotated_text": "<protein>Transcription factor B-cell-specific activator protein</protein> ( <protein>BSAP</protein> ) is differentially expressed in <cell_type>B cells</cell_type> and in subsets of B-cell lymphomas ."}549{"id": "548", "text": "The paired box containing gene PAX-5 encodes the transcription factor BSAP ( B-cell-specific activator protein ) , which plays a key role in B-lymphocyte development .", "annotated_text": "The <dna>paired box containing gene</dna> <dna>PAX-5</dna> encodes the <protein>transcription factor</protein> <protein>BSAP</protein> ( <protein>B-cell-specific activator protein</protein> ) , which plays a key role in B-lymphocyte development ."}550{"id": "549", "text": "Despite its known involvement in a rare subtype of non-Hodgkin 's lymphoma ( NHL ) , a detailed examination of BSAP expression in NHL has not been previously reported .", "annotated_text": "Despite its known involvement in a rare subtype of non-Hodgkin 's lymphoma ( NHL ) , a detailed examination of <protein>BSAP</protein> expression in NHL has not been previously reported ."}551{"id": "550", "text": "In this study , we analyzed normal and malignant lymphoid tissues and cell lines , including 102 cases of B-cell NHL , 23 cases of T- and null-cell NHL , and 18 cases of Hodgkin 's disease .", "annotated_text": "In this study , we analyzed normal and malignant lymphoid tissues and <cell_line>cell lines</cell_line> , including 102 cases of B-cell NHL , 23 cases of T- and null-cell NHL , and 18 cases of Hodgkin 's disease ."}552{"id": "551", "text": "Normal lymphoid tissues showed strong nuclear BSAP expression in mantle zone B cells , less intense reactivity in follicular center B cells , and no expression in cells of the T-cell-rich zones .", "annotated_text": "Normal lymphoid tissues showed strong nuclear <protein>BSAP</protein> expression in <cell_type>mantle zone B cells</cell_type> , less intense reactivity in <cell_type>follicular center B cells</cell_type> , and no expression in cells of the T-cell-rich zones ."}553{"id": "552", "text": "Monocytoid B cells showed weak expression , whereas plasma cells and extrafollicular large transformed B cells were negative .", "annotated_text": "<cell_type>Monocytoid B cells</cell_type> showed weak expression , whereas <cell_type>plasma cells</cell_type> and <cell_type>extrafollicular large transformed B cells</cell_type> were negative ."}554{"id": "553", "text": "Of the 102 B-cell NHLs , 83 ( 81 % ) demonstrated BSAP expression .", "annotated_text": "Of the 102 B-cell NHLs , 83 ( 81 % ) demonstrated <protein>BSAP</protein> expression ."}555{"id": "554", "text": "All of the 13 ( 100 % ) B-cell chronic lymphocytic leukemias ( B-CLLs ) , 21 of ( 100 % ) mantle cells ( MCLs ) , and 20 of 21 ( 95 % ) follicular lymphomas ( FLs ) were positive .", "annotated_text": "All of the 13 ( 100 % ) B-cell chronic lymphocytic leukemias ( B-CLLs ) , 21 of ( 100 % ) <cell_type>mantle cells</cell_type> ( <cell_type>MCLs</cell_type> ) , and 20 of 21 ( 95 % ) follicular lymphomas ( FLs ) were positive ."}556{"id": "555", "text": "Moderate staining intensities were found in most B-CLL and FL cases , whereas most MCLs showed strong reactions , paralleling the strong reactivity of nonmalignant mantle cells .", "annotated_text": "Moderate staining intensities were found in most B-CLL and FL cases , whereas most <cell_type>MCLs</cell_type> showed strong reactions , paralleling the strong reactivity of <cell_type>nonmalignant mantle cells</cell_type> ."}557{"id": "556", "text": "Eight of 12 ( 67 % ) marginal zone lymphoma cases showed negative or low BSAP levels , and 17 of 24 ( 71 % ) large B-cell lymphomas displayed moderate to strong expression .", "annotated_text": "Eight of 12 ( 67 % ) marginal zone lymphoma cases showed negative or low <protein>BSAP</protein> levels , and 17 of 24 ( 71 % ) large B-cell lymphomas displayed moderate to strong expression ."}558{"id": "557", "text": "of the 23 T- and null-cell lymphomas reacted with the BSAP antisera , whereas in Hodgkin 's disease , 2 of 4 ( 50 % ) nodular lymphocytic predominance and 5 of 14 ( 36 % ) classical cases showed weak nuclear or nucleolar BSAP reactions in a fraction of the tumor cells .", "annotated_text": "of the 23 T- and null-cell lymphomas reacted with the <protein>BSAP</protein> antisera , whereas in Hodgkin 's disease , 2 of 4 ( 50 % ) nodular lymphocytic predominance and 5 of 14 ( 36 % ) classical cases showed weak nuclear or nucleolar <protein>BSAP</protein> reactions in a fraction of the <cell_type>tumor cells</cell_type> ."}559{"id": "558", "text": "Western blot analysis showed a 52-kD BSAP band in B-cell lines , but not in non-B-cell or plasma cell lines .", "annotated_text": "Western blot analysis showed a 52-kD <protein>BSAP</protein> band in <cell_line>B-cell lines</cell_line> , but not in <cell_line>non-B-cell or plasma cell lines</cell_line> ."}560{"id": "559", "text": "We conclude that BSAP expression is largely restricted to lymphomas of B-cell lineage and that BSAP expression varies in B-cell subsets and subtypes of B-cell NHL .", "annotated_text": "We conclude that <protein>BSAP</protein> expression is largely restricted to lymphomas of <cell_type>B-cell lineage</cell_type> and that <protein>BSAP</protein> expression varies in <cell_type>B-cell subsets</cell_type> and subtypes of B-cell NHL ."}561{"id": "560", "text": "The high levels of BSAP , especially those found in large-cell lymphomas and in some follicular lymphomas , may be a consequence of deregulated gene expression and suggest a possible involvement of PAX-5 in certain B-cell malignancies .", "annotated_text": "The high levels of <protein>BSAP</protein> , especially those found in <cell_type>large-cell lymphomas</cell_type> and in some <cell_type>follicular lymphomas</cell_type> , may be a consequence of deregulated gene expression and suggest a possible involvement of <dna>PAX-5</dna> in certain B-cell malignancies ."}562{"id": "561", "text": "This is a US government work .", "annotated_text": "This is a US government work ."}563{"id": "562", "text": "There are no restrictions on its use .", "annotated_text": "There are no restrictions on its use ."}564{"id": "563", "text": "Mitogen and growth factor-induced activation of a STAT-like molecule in channel catfish lymphoid cells .", "annotated_text": "Mitogen and growth factor-induced activation of a <protein>STAT-like molecule</protein> in <cell_type>channel catfish lymphoid cells</cell_type> ."}565{"id": "564", "text": "This article describes the identification of a putative STAT molecule in the channel catfish ( Ictalurus punctatus ) , the first report of such a molecule in a 'lower ' vertebrate .", "annotated_text": "This article describes the identification of a <protein>putative STAT molecule</protein> in the channel catfish ( Ictalurus punctatus ) , the first report of such a molecule in a 'lower ' vertebrate ."}566{"id": "565", "text": "A monoclonal antibody against human STAT6 recognizes an approximately 100 kDa molecule that becomes activated and translocates to the nucleus upon both growth factor and mitogen stimulation of catfish leukocytes .", "annotated_text": "A <protein>monoclonal antibody</protein> against <protein>human STAT6</protein> recognizes an approximately <protein>100 kDa molecule</protein> that becomes activated and translocates to the nucleus upon both growth factor and mitogen stimulation of catfish leukocytes ."}567{"id": "566", "text": "This presumed catfish STAT binds the mammalian interferon-gamma activation site , a known motif of mammalian STAT binding , as shown by electromobility shift assays .", "annotated_text": "This presumed <protein>catfish STAT</protein> binds the <dna>mammalian interferon-gamma activation site</dna> , a known motif of mammalian STAT binding , as shown by electromobility shift assays ."}568{"id": "567", "text": "Purification of the proteins present in these DNA complexes confirms that the catfish reactive molecule binds to the interferon-gamma activation site sequence .", "annotated_text": "Purification of the proteins present in these <protein>DNA complexes</protein> confirms that the catfish reactive molecule binds to the <dna>interferon-gamma activation site sequence</dna> ."}569{"id": "568", "text": "These results suggest that STAT molecules have been highly conserved in vertebrate evolution .", "annotated_text": "These results suggest that <protein>STAT molecules</protein> have been highly conserved in vertebrate evolution ."}570{"id": "569", "text": "Isolation and analysis of a T cell clone variant exhibiting constitutively phosphorylated Ser133 cAMP response element-binding protein .", "annotated_text": "Isolation and analysis of a <cell_line>T cell clone variant</cell_line> exhibiting constitutively <protein>phosphorylated Ser133 cAMP response element-binding protein</protein> ."}571{"id": "570", "text": "In driving T cell proliferation , IL-2 stimulates a new program of gene expression that includes proliferating cell nuclear antigen ( PCNA ) , a requisite processivity factor for DNA polymerase delta .", "annotated_text": "In driving T cell proliferation , <protein>IL-2</protein> stimulates a new program of gene expression that includes <protein>proliferating cell nuclear antigen</protein> ( <protein>PCNA</protein> ) , a requisite processivity factor for <protein>DNA polymerase delta</protein> ."}572{"id": "571", "text": "PCNA transcription is regulated in part through tandem CRE sequences in the promoter and CRE binding proteins ; IL-2 stimulates CREB phosphorylation in the resting cloned T lymphocyte , L2 .", "annotated_text": "<protein>PCNA</protein> transcription is regulated in part through tandem <dna>CRE sequences</dna> in the <protein>promoter and CRE binding proteins</protein> ; <protein>IL-2</protein> stimulates CREB phosphorylation in the <cell_line>resting cloned T lymphocyte</cell_line> , <cell_line>L2</cell_line> ."}573{"id": "572", "text": "After culturing L2 cells for greater than 91 days , we consistently isolate a stable variant that exhibits constitutive CREB phosphorylation .", "annotated_text": "After culturing <cell_line>L2 cells</cell_line> for greater than 91 days , we consistently isolate a stable variant that exhibits constitutive CREB phosphorylation ."}574{"id": "573", "text": "L2 and L2 variant cells were tested for IL-2 responsiveness and rapamycin sensitivity with respect to specific kinase activity , PCNA expression and proliferation .", "annotated_text": "<cell_line>L2 and L2 variant cells</cell_line> were tested for <protein>IL-2</protein> responsiveness and rapamycin sensitivity with respect to specific kinase activity , PCNA expression and proliferation ."}575{"id": "574", "text": "In L2 cells , IL-2 stimulated and rapamycin inhibited the following : cAMP-independent CREB kinase activity , PCNA expression and proliferation .", "annotated_text": "In <cell_line>L2 cells</cell_line> , <protein>IL-2</protein> stimulated and rapamycin inhibited the following : cAMP-independent <protein>CREB kinase</protein> activity , PCNA expression and proliferation ."}576{"id": "575", "text": "In L2 variant cells , CREB kinase activity was constitutively high ; IL-2 stimulated and rapamycin blocked PCNA expression and proliferation .", "annotated_text": "In <cell_line>L2 variant cells</cell_line> , <protein>CREB kinase</protein> activity was constitutively high ; <protein>IL-2</protein> stimulated and rapamycin blocked PCNA expression and proliferation ."}577{"id": "576", "text": "These results indicate that IL-2 induces a rapamycin-sensitive , cAMP-independent CREB kinase activity in L2 cells .", "annotated_text": "These results indicate that <protein>IL-2</protein> induces a rapamycin-sensitive , cAMP-independent <protein>CREB kinase</protein> activity in <cell_line>L2 cells</cell_line> ."}578{"id": "577", "text": "However , phosphorylation of CREB alone is not sufficient to drive PCNA expression and L2 cell proliferation in the absence of IL-2 .", "annotated_text": "However , phosphorylation of <protein>CREB</protein> alone is not sufficient to drive <protein>PCNA</protein> expression and L2 cell proliferation in the absence of <protein>IL-2</protein> ."}579{"id": "578", "text": "Serotonin derivative , N- ( p-coumaroyl ) serotonin , inhibits the production of TNF-alpha , IL-1alpha , IL-1beta , and IL-6 by endotoxin-stimulated human blood monocytes .", "annotated_text": "Serotonin derivative , N- ( p-coumaroyl ) serotonin , inhibits the production of <protein>TNF-alpha</protein> , <protein>IL-1alpha</protein> , <protein>IL-1beta</protein> , and <protein>IL-6</protein> by <cell_type>endotoxin-stimulated human blood monocytes</cell_type> ."}580{"id": "579", "text": "We have reported that N- ( p-coumaroyl ) serotonin ( CS ) and its derivatives with antioxidative activity are present in safflower seeds .", "annotated_text": "We have reported that N- ( p-coumaroyl ) serotonin ( CS ) and its derivatives with antioxidative activity are present in safflower seeds ."}581{"id": "580", "text": "As reactive oxygen species ( ROS ) are implicated in the signaling of lipopolysaccharide ( LPS ) , we examined whether CS has a suppressive effect on inflammatory cytokine generation from human monocyte s in vitro .", "annotated_text": "As reactive oxygen species ( ROS ) are implicated in the signaling of lipopolysaccharide ( LPS ) , we examined whether CS has a suppressive effect on <protein>inflammatory cytokine</protein> generation from <cell_type>human monocyte</cell_type> s in vitro ."}582{"id": "581", "text": "CS at 50-200 microM reduced tumor necrosis factor ( TNF ) , interleukin-1 ( IL-1 ) , and IL-6 activities in the culture supernatants from LPS-stimulated human blood monocytes without cytotoxicity .", "annotated_text": "CS at 50-200 microM reduced <protein>tumor necrosis factor</protein> ( <protein>TNF</protein> ) , <protein>interleukin-1</protein> ( <protein>IL-1</protein> ) , and <protein>IL-6</protein> activities in the culture supernatants from <cell_line>LPS-stimulated human blood monocytes</cell_line> without cytotoxicity ."}583{"id": "582", "text": "ELISA assay revealed that the production of TNF-alpha , IL-1alpha , IL-1beta , and IL-6 was inhibited by CS .", "annotated_text": "ELISA assay revealed that the production of <protein>TNF-alpha</protein> , <protein>IL-1alpha</protein> , <protein>IL-1beta</protein> , and <protein>IL-6</protein> was inhibited by CS ."}584{"id": "583", "text": "Northern blot analysis showed that LPS-induced expression of these cytokine mRNA in monocytes was suppressed by CS .", "annotated_text": "Northern blot analysis showed that LPS-induced expression of these <rna>cytokine mRNA</rna> in <cell_type>monocytes</cell_type> was suppressed by CS ."}585{"id": "584", "text": "NF-kappaB activation was also inhibited by CS .", "annotated_text": "NF-kappaB activation was also inhibited by CS ."}586{"id": "585", "text": "These findings indicate that CS has a suppressive effect on proinflammatory cytokine production from monocytes , and this effect is based in part on the suppression of cytokine mRNA expression through inhibition of NF-kappaB activation .", "annotated_text": "These findings indicate that CS has a suppressive effect on proinflammatory cytokine production from <cell_type>monocytes</cell_type> , and this effect is based in part on the suppression of <rna>cytokine mRNA</rna> expression through inhibition of <protein>NF-kappaB</protein> activation ."}587{"id": "586", "text": "Elevated expression of differentiation inhibitory factor nm23 mRNA in monoblastic crisis of a patient with chronic myelogenous leukemia .", "annotated_text": "Elevated expression of <rna>differentiation inhibitory factor nm23 mRNA</rna> in monoblastic crisis of a patient with chronic myelogenous leukemia ."}588{"id": "587", "text": "Differentiation inhibitory factor nm23 gene has been found to be expressed in high quantities in acute myelogenous leukemia ( AML ) , especially in acute monocytic leukemia ( AML-M5 ) and is suggested as a new prognostic factor in AML-M5 .", "annotated_text": "<protein>Differentiation inhibitory factor</protein> <dna>nm23 gene</dna> has been found to be expressed in high quantities in acute myelogenous leukemia ( AML ) , especially in acute monocytic leukemia ( AML-M5 ) and is suggested as a new prognostic factor in AML-M5 ."}589{"id": "588", "text": "We report an example of elevated expression of nm23 mRNA in a patient with chronic myelogenous leukemia ( CML ) who developed monoblastic crisis .", "annotated_text": "We report an example of elevated expression of <rna>nm23 mRNA</rna> in a patient with chronic myelogenous leukemia ( CML ) who developed monoblastic crisis ."}590{"id": "589", "text": "Relative levels of nm23-H1 and -H2 mRNA extracted from the patient 's peripheral blood mononuclear cells and bone marrow mononuclear cells were measured by quantitative reverse transcriptase polymerase chain reaction .", "annotated_text": "Relative levels of <rna>nm23-H1 and -H2 mRNA</rna> extracted from the patient 's <cell_type>peripheral blood mononuclear cells</cell_type> and <cell_type>bone marrow mononuclear cells</cell_type> were measured by quantitative reverse transcriptase polymerase chain reaction ."}591{"id": "590", "text": "The level of nm23-H1 mRNA in CML cells at the chronic phase was as high as that in bone marrow cells from healthy volunteers .", "annotated_text": "The level of <rna>nm23-H1 mRNA</rna> in <cell_line>CML cells</cell_line> at the chronic phase was as high as that in <cell_type>bone marrow cells</cell_type> from healthy volunteers ."}592{"id": "591", "text": "The mRNA level of nm23-H2 was slightly below the normal level .", "annotated_text": "The mRNA level of <protein>nm23-H2</protein> was slightly below the normal level ."}593{"id": "592", "text": "At blastic crisis , however , expression of both nm23-H1 and -H2 mRNA was elevated to about three to nine times of that at the chronic phase .", "annotated_text": "At blastic crisis , however , expression of both <rna>nm23-H1 and -H2 mRNA</rna> was elevated to about three to nine times of that at the chronic phase ."}594{"id": "593", "text": "Proliferated blastic cells were positive for non-specific esterase , and the serum lysozyme level was elevated and diagnosed as monoblastic crisis .", "annotated_text": "<cell_type>Proliferated blastic cells</cell_type> were positive for <protein>non-specific esterase</protein> , and the serum lysozyme level was elevated and diagnosed as monoblastic crisis ."}595{"id": "594", "text": "The patient received combined chemotherapy but response was partial .", "annotated_text": "The patient received combined chemotherapy but response was partial ."}596{"id": "595", "text": "These findings are compatible with our previous report that nm23 gene is overexpressed in monocytic leukemia .", "annotated_text": "These findings are compatible with our previous report that <dna>nm23 gene</dna> is overexpressed in monocytic leukemia ."}597{"id": "596", "text": "Increased transcription decreases the spontaneous mutation rate at the thymidine kinase locus in human cells .", "annotated_text": "Increased transcription decreases the spontaneous mutation rate at the <dna>thymidine kinase locus</dna> in <cell_type>human cells</cell_type> ."}598{"id": "597", "text": "Transcription increases DNA repair efficiency and modulates the distribution of certain types of DNA damage .", "annotated_text": "Transcription increases DNA repair efficiency and modulates the distribution of certain types of DNA damage ."}599{"id": "598", "text": "Furthermore , increased transcription level stimulates spontaneous mutation rate in yeast .", "annotated_text": "Furthermore , increased transcription level stimulates spontaneous mutation rate in yeast ."}600{"id": "599", "text": "We explored whether transcription level affects spontaneous mutation rate in human cells .", "annotated_text": "We explored whether transcription level affects spontaneous mutation rate in <cell_type>human cells</cell_type> ."}601{"id": "600", "text": "We first developed two thymidine kinase ( tk ) inducible human cell lines using the Gal4-Estrogen receptor system .", "annotated_text": "We first developed two <cell_line>thymidine kinase ( tk ) inducible human cell lines</cell_line> using the Gal4-Estrogen receptor system ."}602{"id": "601", "text": "In our TK6i-G3 and G9 tk heterozygous cell lines , the active tk allele is linked to an inducible promoter element .", "annotated_text": "In our <cell_line>TK6i-G3 and G9 tk heterozygous cell lines</cell_line> , the active <dna>tk allele</dna> is linked to an inducible <dna>promoter element</dna> ."}603{"id": "602", "text": "Tk mRNA is induced following treatment with estrogen .", "annotated_text": "<rna>Tk mRNA</rna> is induced following treatment with estrogen ."}604{"id": "603", "text": "Spontaneous mutation rate was significantly decreased in human cell lines after induction in contrast to the report in yeast .", "annotated_text": "Spontaneous mutation rate was significantly decreased in <cell_line>human cell lines</cell_line> after induction in contrast to the report in yeast ."}605{"id": "604", "text": "Thus , humans may have evolved different or additional mechanisms to deal with transcription related spontaneous mutagenesis .", "annotated_text": "Thus , humans may have evolved different or additional mechanisms to deal with transcription related spontaneous mutagenesis ."}606{"id": "605", "text": "Copyright 1998 Elsevier Science B.V .", "annotated_text": "Copyright 1998 Elsevier Science B.V ."}607{"id": "606", "text": "All rights reserved .", "annotated_text": "All rights reserved ."}608{"id": "607", "text": "Mutation of BCL-6 gene in normal B cells by the process of somatic hypermutation of Ig genes .", "annotated_text": "Mutation of <dna>BCL-6 gene</dna> in normal <cell_type>B cells</cell_type> by the process of somatic hypermutation of <dna>Ig genes</dna> ."}609{"id": "608", "text": "Immunoglobulin ( Ig ) genes are hypermutated in B lymphocytes that are the precursors to memory B cells .", "annotated_text": "<dna>Immunoglobulin ( Ig ) genes</dna> are hypermutated in <cell_type>B lymphocytes</cell_type> that are the precursors to <cell_type>memory B cells</cell_type> ."}610{"id": "609", "text": "The mutations are linked to transcription initiation , but non-Ig promoters are permissible for the mutation process ; thus , other genes expressed in mutating B cells may also be subject to somatic hypermutation .", "annotated_text": "The mutations are linked to transcription initiation , but <dna>non-Ig promoters</dna> are permissible for the mutation process ; thus , other genes expressed in mutating <cell_type>B cells</cell_type> may also be subject to somatic hypermutation ."}611{"id": "610", "text": "Significant mutations were not observed in c-MYC , S14 , or alpha-fetoprotein ( AFP ) genes , but BCL-6 was highly mutated in a large proportion of memory B cells of normal individuals .", "annotated_text": "Significant mutations were not observed in <dna>c-MYC , S14 , or alpha-fetoprotein ( AFP ) genes</dna> , but <protein>BCL-6</protein> was highly mutated in a large proportion of <cell_type>memory B cells</cell_type> of normal individuals ."}612{"id": "611", "text": "The mutation pattern was similar to that of Ig genes .", "annotated_text": "The mutation pattern was similar to that of <dna>Ig genes</dna> ."}613{"id": "612", "text": "CD28-mediated activation in CD45RA+ and CD45RO+ T cells : enhanced levels of reactive oxygen intermediates and c-Rel nuclear translocation in CD45RA+ cells .", "annotated_text": "CD28-mediated activation in <cell_type>CD45RA+ and CD45RO+ T cells</cell_type> : enhanced levels of reactive oxygen intermediates and c-Rel nuclear translocation in <cell_type>CD45RA+ cells</cell_type> ."}614{"id": "613", "text": "We have analyzed the effect of complete T cell activation ( anti-CD3 plus anti-CD28 ) on the activation of NF-kappaB in CD45RA+ ( naive ) and CD45RO+ ( memory/effector ) T cells .", "annotated_text": "We have analyzed the effect of complete T cell activation ( anti-CD3 plus anti-CD28 ) on the activation of <protein>NF-kappaB</protein> in <cell_type>CD45RA+ ( naive ) and CD45RO+ ( memory/effector ) T cells</cell_type> ."}615{"id": "614", "text": "Long exposure ( 24 h ) induced stronger NF-kappaB DNA binding in CD45RA+ cells than in CD45RO+ cells .", "annotated_text": "Long exposure ( 24 h ) induced stronger <protein>NF-kappaB</protein> DNA binding in <cell_type>CD45RA+ cells</cell_type> than in <cell_type>CD45RO+ cells</cell_type> ."}616{"id": "615", "text": "Analysis of the nuclear c-Rel protein indicated that after anti-CD3+anti-CD28 stimulation the level of c-Rel was higher in CD45RA+ cells .", "annotated_text": "Analysis of the <protein>nuclear c-Rel protein</protein> indicated that after anti-CD3+anti-CD28 stimulation the level of <protein>c-Rel</protein> was higher in <cell_type>CD45RA+ cells</cell_type> ."}617{"id": "616", "text": "Analysis of the cytoplasmic inhibitor IkappaBalpha indicated that anti-CD3+anti-CD28 stimulation induced a long-lasting degradation in CD45RA+ cells but in CD45RO+ cells the degradation process was more rapid .", "annotated_text": "Analysis of the <protein>cytoplasmic inhibitor</protein> <protein>IkappaBalpha</protein> indicated that anti-CD3+anti-CD28 stimulation induced a long-lasting degradation in <cell_type>CD45RA+ cells</cell_type> but in <cell_type>CD45RO+ cells</cell_type> the degradation process was more rapid ."}618{"id": "617", "text": "Because the CD28 costimulus is known to induce the production of reactive oxygen intermediates ( ROIs ) , the intracellular ROI levels in CD45RA+ and CD45RO+ cells were compared by flow cytometry .", "annotated_text": "Because the <protein>CD28</protein> costimulus is known to induce the production of reactive oxygen intermediates ( ROIs ) , the intracellular ROI levels in <cell_type>CD45RA+ and CD45RO+ cells</cell_type> were compared by flow cytometry ."}619{"id": "618", "text": "ROIs were produced in both cell types , but more strongly in CD45RA+ cells .", "annotated_text": "ROIs were produced in both cell types , but more strongly in <cell_type>CD45RA+ cells</cell_type> ."}620{"id": "619", "text": "The data presented in this study further emphasize the differences between CD45RA+ and CD45RO+ T lymphocytes in ROI-dependent signaling pathways .", "annotated_text": "The data presented in this study further emphasize the differences between <cell_type>CD45RA+ and CD45RO+ T lymphocytes</cell_type> in ROI-dependent signaling pathways ."}621{"id": "620", "text": "Non-Hodgkin 's lymphoma involving bilateral breasts [ see comments ]", "annotated_text": "Non-Hodgkin 's lymphoma involving bilateral breasts [ see comments ]"}622{"id": "621", "text": "We describe here two cases of diffuse large cell type non-Hodgkin 's lymphoma affecting the bilateral breasts .", "annotated_text": "We describe here two cases of diffuse large cell type non-Hodgkin 's lymphoma affecting the bilateral breasts ."}623{"id": "622", "text": "The contralateral tumor in one case appeared 17 months after the first mastectomy , whereas the bilateral tumors occurred concurrently in the other patient who was pregnant and showed widespread dissemination at initial presentation .", "annotated_text": "The contralateral tumor in one case appeared 17 months after the first mastectomy , whereas the bilateral tumors occurred concurrently in the other patient who was pregnant and showed widespread dissemination at initial presentation ."}624{"id": "623", "text": "Lymphoma cells from both cases showed the mature B-cell immunophenotype and had rearrangements of the BCL6 gene .", "annotated_text": "<cell_type>Lymphoma cells</cell_type> from both cases showed the mature B-cell immunophenotype and had rearrangements of the <dna>BCL6 gene</dna> ."}625{"id": "624", "text": "Both patients developed progressive disease despite chemo-radiotherapy and died of leukemic manifestations .", "annotated_text": "Both patients developed progressive disease despite chemo-radiotherapy and died of leukemic manifestations ."}626{"id": "625", "text": "There were no apparent pathological features of lymphomas of mucosa-associated lymphoid tissue origin", "annotated_text": "There were no apparent pathological features of lymphomas of mucosa-associated lymphoid tissue origin"}627{"id": "626", "text": "Biochemical characterization of MIP-1 alpha nuclear protein .", "annotated_text": "Biochemical characterization of <protein>MIP-1 alpha nuclear protein</protein> ."}628{"id": "627", "text": "A family of hematopoietic specific transcription factors , MIP-1 alpha nuclear protein ( MNP ) family , has recently been identified .", "annotated_text": "A family of <protein>hematopoietic specific transcription factors</protein> , <protein>MIP-1 alpha nuclear protein ( MNP ) family</protein> , has recently been identified ."}629{"id": "628", "text": "They are intimately involved in regulating the transcription of the huMIP-1 alpha gene in monocytes , T-cells , and transformed B-cells .", "annotated_text": "They are intimately involved in regulating the transcription of the <dna>huMIP-1 alpha gene</dna> in <cell_type>monocytes</cell_type> , <cell_type>T-cells</cell_type> , and <cell_type>transformed B-cells</cell_type> ."}630{"id": "629", "text": "One member of the family ( MNP-1 ) is essential for promoter activity in monocytes and B-cells , while another ( MNP-2 ) is required for full promotor activity in T-cells .", "annotated_text": "One member of the family ( <protein>MNP-1</protein> ) is essential for promoter activity in <cell_type>monocytes</cell_type> and <cell_type>B-cells</cell_type> , while another ( <protein>MNP-2</protein> ) is required for full promotor activity in <cell_type>T-cells</cell_type> ."}631{"id": "630", "text": "A third member of the family ( MNP-3 ) is expressed in PMA induced HL60 cells and probably has a role in monocyte differentiation .", "annotated_text": "A third member of the family ( <protein>MNP-3</protein> ) is expressed in <cell_line>PMA induced HL60 cells</cell_line> and probably has a role in monocyte differentiation ."}632{"id": "631", "text": "In this communication we demonstrate by two techniques that MNP-1 and MNP-2 are distinct but related factors , and we present further evidence to show that MNP-1 acts as a heterodimer .", "annotated_text": "In this communication we demonstrate by two techniques that <protein>MNP-1</protein> and <protein>MNP-2</protein> are distinct but related factors , and we present further evidence to show that <protein>MNP-1</protein> acts as a <protein>heterodimer</protein> ."}633{"id": "632", "text": "Bcl-3 expression and nuclear translocation are induced by granulocyte-macrophage colony-stimulating factor and erythropoietin in proliferating human erythroid precursors .", "annotated_text": "<protein>Bcl-3</protein> expression and nuclear translocation are induced by <protein>granulocyte-macrophage colony-stimulating factor</protein> and <protein>erythropoietin</protein> in <cell_type>proliferating human erythroid precursors</cell_type> ."}634{"id": "633", "text": "Bcl-3 is a proto-oncogene involved in the chromosomal translocation t ( 14 ; 19 ) found in some patients with chronic lymphocytic leukemia .", "annotated_text": "<protein>Bcl-3</protein> is a <dna>proto-oncogene</dna> involved in the chromosomal translocation <dna>t ( 14 ; 19 )</dna> found in some patients with chronic lymphocytic leukemia ."}635{"id": "634", "text": "It shares structural similarities with and is a member of the IkappaB family of proteins .", "annotated_text": "It shares structural similarities with and is a member of the <protein>IkappaB family</protein> of proteins ."}636{"id": "635", "text": "In this report , involvement of Bcl-3 in hematopoietic growth factor-stimulated erythroid proliferation and differentiation was examined .", "annotated_text": "In this report , involvement of <protein>Bcl-3</protein> in hematopoietic growth factor-stimulated erythroid proliferation and differentiation was examined ."}637{"id": "636", "text": "In TF-1 cells , an erythroleukemia cell line , granulocyte-macrophage colony-stimulating factor ( GM-CSF ) and erythropoietin ( Epo ) greatly enhanced Bcl-3 expression at both the protein and mRNA levels in association with stimulation of proliferation .", "annotated_text": "In <cell_line>TF-1 cells</cell_line> , an <cell_line>erythroleukemia cell line</cell_line> , <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) and <protein>erythropoietin</protein> ( <protein>Epo</protein> ) greatly enhanced <protein>Bcl-3</protein> expression at both the protein and mRNA levels in association with stimulation of proliferation ."}638{"id": "637", "text": "Bcl-3 protein was also highly expressed in early burst-forming unit-erythroid ( BFU-E ) -derived erythroid precursors ( day 7 ) and decreased during maturation ( days 10 and 14 ) , suggesting that Bcl-3 is involved in normal erythroid proliferation .", "annotated_text": "<protein>Bcl-3</protein> protein was also highly expressed in <cell_type>early burst-forming unit-erythroid ( BFU-E ) -derived erythroid precursors</cell_type> ( day 7 ) and decreased during maturation ( days 10 and 14 ) , suggesting that <protein>Bcl-3</protein> is involved in normal erythroid proliferation ."}639{"id": "638", "text": "In these hematopoietic cells , Bcl-3 was hyperphosphorylated .", "annotated_text": "In these <cell_type>hematopoietic cells</cell_type> , <protein>Bcl-3</protein> was hyperphosphorylated ."}640{"id": "639", "text": "GM-CSF and Epo modulated the subcellular localization of Bcl-3 .", "annotated_text": "<protein>GM-CSF</protein> and <protein>Epo</protein> modulated the subcellular localization of <protein>Bcl-3</protein> ."}641{"id": "640", "text": "Upon stimulation of TF-1 cells with GM-CSF or Epo , the nuclear translocation of Bcl-3 was dramatically enhanced .", "annotated_text": "Upon stimulation of <cell_line>TF-1 cells</cell_line> with <protein>GM-CSF</protein> or <protein>Epo</protein> , the nuclear translocation of <protein>Bcl-3</protein> was dramatically enhanced ."}642{"id": "641", "text": "Overexpression of Bcl-3 in TF-1 cells by transient transfection along with the NF-kappaB factors p50 or p52 resulted in significant induction of an human immunodeficiency virus-type 1 ( HIV-1 ) kappaB-TATA-luceriferase reporter plasmid , demonstrating that Bcl-3 has a positive role in transactivation of kappaB-containing genes in erythroid cells .", "annotated_text": "Overexpression of <protein>Bcl-3</protein> in <cell_line>TF-1 cells</cell_line> by transient transfection along with the <protein>NF-kappaB factors p50 or p52</protein> resulted in significant induction of an <dna>human immunodeficiency virus-type 1 ( HIV-1 ) kappaB-TATA-luceriferase reporter plasmid</dna> , demonstrating that <protein>Bcl-3</protein> has a positive role in transactivation of <dna>kappaB-containing genes</dna> in <cell_type>erythroid cells</cell_type> ."}643{"id": "642", "text": "Stimulation with GM-CSF enhanced c-myb mRNA expression in these cells .", "annotated_text": "Stimulation with <protein>GM-CSF</protein> enhanced <rna>c-myb mRNA</rna> expression in these cells ."}644{"id": "643", "text": "Bcl-3 in nuclear extracts of TF-1 cells bound to a kappaB enhancer in the c-myb promoter together with NF-kappaB2/p52 and this binding activity was enhanced by GM-CSF stimulation .", "annotated_text": "<protein>Bcl-3</protein> in nuclear extracts of <cell_line>TF-1 cells</cell_line> bound to a <dna>kappaB enhancer</dna> in the <dna>c-myb promoter</dna> together with <protein>NF-kappaB2/p52</protein> and this binding activity was enhanced by <protein>GM-CSF</protein> stimulation ."}645{"id": "644", "text": "Furthermore , cotransfection of Bcl-3 with p52 or p50 in TF-1 cells resulted in significant activation of a c-myb kappaB-TATA-luceriferase reporter plasmid .", "annotated_text": "Furthermore , cotransfection of <protein>Bcl-3</protein> with <protein>p52</protein> or <protein>p50</protein> in <cell_line>TF-1 cells</cell_line> resulted in significant activation of a <dna>c-myb kappaB-TATA-luceriferase reporter plasmid</dna> ."}646{"id": "645", "text": "These findings suggest that Bcl-3 may participate in the transcriptional regulation of certain kappaB-containing genes involved in hematopoiesis , including c-myb .", "annotated_text": "These findings suggest that <protein>Bcl-3</protein> may participate in the transcriptional regulation of certain <dna>kappaB-containing genes</dna> involved in hematopoiesis , including <dna>c-myb</dna> ."}647{"id": "646", "text": "Copyright 1998 by The American Society of Hematology .", "annotated_text": "Copyright 1998 by The American Society of Hematology ."}648{"id": "647", "text": "5-Lipoxygenase compartmentalization in granulocytic cells is modulated by an internal bipartite nuclear localizing sequence and nuclear factor kappa B complex formation .", "annotated_text": "<protein>5-Lipoxygenase</protein> compartmentalization in granulocytic cells is modulated by an <protein>internal bipartite nuclear localizing sequence</protein> and <protein>nuclear factor kappa B complex</protein> formation ."}649{"id": "648", "text": "A region of basic amino acids spanning residues 639-656 in the human 5-lipoxygenase sequence resembles a consensus bipartite nuclear localizing sequence .", "annotated_text": "A region of basic amino acids spanning <protein>residues 639-656</protein> in the <protein>human 5-lipoxygenase sequence</protein> resembles a <protein>consensus bipartite nuclear localizing sequence</protein> ."}650{"id": "649", "text": "A synthetic peptide consisting of the Kaposi fibroblast growth factor signal sequence fused to the 5-lipoxygenase639-656 bipartite nuclear localizing sequence has a prominent inhibitory effect on 5-lipoxygenase catalysis in granulocytic HL-60 cells activated by calcium ionophor A23187 .", "annotated_text": "A synthetic peptide consisting of the <protein>Kaposi fibroblast growth factor signal sequence</protein> fused to the <protein>5-lipoxygenase639-656 bipartite nuclear localizing sequence</protein> has a prominent inhibitory effect on <protein>5-lipoxygenase</protein> catalysis in granulocytic <cell_line>HL-60 cells</cell_line> activated by calcium ionophor A23187 ."}651{"id": "650", "text": "Recombinant 5-lipoxygenase was not affected by the peptide .", "annotated_text": "Recombinant <protein>5-lipoxygenase</protein> was not affected by the peptide ."}652{"id": "651", "text": "The peptide also inhibited redistribution of 5-lipoxygenase from the cytosol to the nuclear membrane of HL-60 cells stimulated by A23187 .", "annotated_text": "The peptide also inhibited redistribution of <protein>5-lipoxygenase</protein> from the cytosol to the nuclear membrane of <cell_line>HL-60 cells</cell_line> stimulated by A23187 ."}653{"id": "652", "text": "5-Lipoxygenase protein was detected in nuclear factor kappaB ( NF-kappaB ) p65 subunit immunoprecipitate fractions prepared from HL-60 cell lysates .", "annotated_text": "<protein>5-Lipoxygenase protein</protein> was detected in <protein>nuclear factor kappaB ( NF-kappaB ) p65 subunit</protein> immunoprecipitate fractions prepared from <cell_line>HL-60 cell</cell_line> lysates ."}654{"id": "653", "text": "The amount of 5-lipoxygenase protein coimmunoprecipitated by NF-kappaB antiserum was increased following A23187 stimulation .", "annotated_text": "The amount of <protein>5-lipoxygenase protein</protein> coimmunoprecipitated by NF-kappaB antiserum was increased following A23187 stimulation ."}655{"id": "654", "text": "In cells treated with agents that block 5-lipoxygenase translocation to the nucleus , 5-lipoxygenase protein appearing in the NF-kappaB immunoprecipitate was diminished .", "annotated_text": "In cells treated with agents that block <protein>5-lipoxygenase</protein> translocation to the nucleus , <protein>5-lipoxygenase</protein> protein appearing in the <protein>NF-kappaB</protein> immunoprecipitate was diminished ."}656{"id": "655", "text": "Our results implicate an internal bipartite nuclear localizing sequence as a regulatory domain that modulates 5-lipoxygenase redistribution and catalysis in granulocytic cells .", "annotated_text": "Our results implicate an <protein>internal bipartite nuclear localizing sequence</protein> as a regulatory domain that modulates <protein>5-lipoxygenase</protein> redistribution and catalysis in <cell_type>granulocytic cells</cell_type> ."}657{"id": "656", "text": "Additionally , our results suggest that molecular determinants which govern 5-lipoxygenase and NF-kappaB redistribution to the nucleus may be coordinately controlled in granulocytic cells .", "annotated_text": "Additionally , our results suggest that molecular determinants which govern 5-lipoxygenase and NF-kappaB redistribution to the nucleus may be coordinately controlled in <cell_type>granulocytic cells</cell_type> ."}658{"id": "657", "text": "Copyright 1998 Academic Press .", "annotated_text": "Copyright 1998 Academic Press ."}659{"id": "658", "text": "Inhibition of CD28/CD3-mediated costimulation of naive and memory human T lymphocytes by intracellular incorporation of polyclonal antibodies specific for the activator protein-1 transcriptional complex .", "annotated_text": "Inhibition of CD28/CD3-mediated costimulation of <cell_type>naive and memory human T lymphocytes</cell_type> by intracellular incorporation of <protein>polyclonal antibodies</protein> specific for the <protein>activator protein-1 transcriptional complex</protein> ."}660{"id": "659", "text": "A number of indirect methods have been utilized in demonstrating activator protein-1 transcription factor function in IL-2 promoter activity .", "annotated_text": "A number of indirect methods have been utilized in demonstrating <protein>activator protein-1</protein> transcription factor function in IL-2 promoter activity ."}661{"id": "660", "text": "However , there has been no direct demonstration that activator protein-1 is involved in CD28-dependent costimulation of IL-2 gene transcription in freshly isolated naive and memory human T lymphocytes .", "annotated_text": "However , there has been no direct demonstration that <protein>activator protein-1</protein> is involved in CD28-dependent costimulation of <dna>IL-2 gene</dna> transcription in freshly isolated <cell_type>naive and memory human T lymphocytes</cell_type> ."}662{"id": "661", "text": "To address this issue , the method of scrape loading was applied to purified peripheral blood T lymphocytes .", "annotated_text": "To address this issue , the method of scrape loading was applied to <cell_type>purified peripheral blood T lymphocytes</cell_type> ."}663{"id": "662", "text": "Since scrape loading relies on adherent cells , peripheral blood human T ( PB-T ) cells were immobilized on the nonspecific cell attachment factor poly-L-lysine .", "annotated_text": "Since scrape loading relies on <cell_type>adherent cells</cell_type> , <cell_type>peripheral blood human T ( PB-T ) cells</cell_type> were immobilized on the nonspecific cell attachment factor poly-L-lysine ."}664{"id": "663", "text": "Cells scraped off poly-L-lysine in the presence of Ig FITC efficiently incorporated Ig , with relatively uniform fluorescence .", "annotated_text": "Cells scraped off poly-L-lysine in the presence of <protein>Ig FITC</protein> efficiently incorporated Ig , with relatively uniform fluorescence ."}665{"id": "664", "text": "T cells retained their physical parameters as measured by forward and side light scatter , and functional activity as measured by costimulation of proliferation and IL-2 production after being scraped off this substrate .", "annotated_text": "T cells retained their physical parameters as measured by forward and side light scatter , and functional activity as measured by costimulation of proliferation and <protein>IL-2</protein> production after being scraped off this substrate ."}666{"id": "665", "text": "CD28/CD3-costimulated T cells produced intracellular IL-2 from all subsets measured ( CD4+ , CD4- , CD45RO+ , and CD45RO- ) .", "annotated_text": "<cell_type>CD28/CD3-costimulated T cells</cell_type> produced intracellular <protein>IL-2</protein> from all subsets measured ( <cell_type>CD4+</cell_type> , <cell_type>CD4-</cell_type> , <cell_type>CD45RO+</cell_type> , and <cell_type>CD45RO-</cell_type> ) ."}667{"id": "666", "text": "IL-2 production and intracellular accumulation in nonscraped PB-T cells activated with CD28/CD3 coligation were skewed favoring CD45RO+ and CD4+ subsets , as was IL-2 production in scraped PB-T cells .", "annotated_text": "<protein>IL-2</protein> production and intracellular accumulation in nonscraped <cell_type>PB-T cells</cell_type> activated with CD28/CD3 coligation were skewed favoring <cell_type>CD45RO+ and CD4+ subsets</cell_type> , as was <protein>IL-2</protein> production in scraped <cell_type>PB-T cells</cell_type> ."}668{"id": "667", "text": "The intracellular incorporation of Abs specific for c-Fos and c-Jun family members by scrape loading inhibited the production and intracellular accumulation of IL-2 within 6 h of costimulation with PMA/ionomycin , or costimulation by CD28 and CD3 ligation .", "annotated_text": "The intracellular incorporation of Abs specific for <protein>c-Fos and c-Jun family members</protein> by scrape loading inhibited the production and intracellular accumulation of <protein>IL-2</protein> within 6 h of costimulation with PMA/ionomycin , or costimulation by CD28 and CD3 ligation ."}669{"id": "668", "text": "Scrape loading thus provides an efficient mechanism for intracellular incorporation of macromolecules , and the first direct evidence that c-Fos and c-Jun are involved in transcription of the IL-2 gene within its correct chromosomal context , in resting human T lymphocyte subpopulations .", "annotated_text": "Scrape loading thus provides an efficient mechanism for intracellular incorporation of macromolecules , and the first direct evidence that <protein>c-Fos</protein> and <protein>c-Jun</protein> are involved in transcription of the <dna>IL-2 gene</dna> within its correct chromosomal context , in resting human T lymphocyte subpopulations ."}670{"id": "669", "text": "Differential expression of Nur77 family members in human T-lymphotropic virus type 1-infected cells : transactivation of the TR3/nur77 gene by Tax protein .", "annotated_text": "Differential expression of <protein>Nur77 family members</protein> in <cell_type>human T-lymphotropic virus type 1-infected cells</cell_type> : transactivation of the <dna>TR3/nur77 gene</dna> by <protein>Tax protein</protein> ."}671{"id": "670", "text": "We analyzed the differential expression and regulation of three members of the Nur77 transcription factor family by the human T-lymphotropic virus type 1 ( HTLV-1 ) Tax protein .", "annotated_text": "We analyzed the differential expression and regulation of three members of the <protein>Nur77 transcription factor family</protein> by the human T-lymphotropic virus type 1 ( HTLV-1 ) <protein>Tax protein</protein> ."}672{"id": "671", "text": "We have demonstrated that in both HTLV-1-infected cells and Tax-expressing JPX-9 cells , TR3/nur77 is highly expressed , whereas neither NOR-1 nor NOT expression is detectable .", "annotated_text": "We have demonstrated that in both <cell_type>HTLV-1-infected cells</cell_type> and <cell_line>Tax-expressing JPX-9 cells</cell_line> , <protein>TR3/nur77</protein> is highly expressed , whereas neither NOR-1 nor NOT expression is detectable ."}673{"id": "672", "text": "Transient transfection analysis further confirmed the Tax transactivation of the TR3/nur77 promoter but not the NOR-1 promoter in different cell types .", "annotated_text": "Transient transfection analysis further confirmed the <protein>Tax</protein> transactivation of the <protein>TR3/nur77</protein> promoter but not the <dna>NOR-1 promoter</dna> in different cell types ."}674{"id": "673", "text": "Furthermore , expression of a luciferase reporter gene driven by the NGFI-B ( rat homolog of TR3/Nur77 ) response element ( NBRE ) provided evidence that Tax -mediated transactivation resulted in the induction of a functional protein .", "annotated_text": "Furthermore , expression of a <dna>luciferase reporter gene</dna> driven by the <dna>NGFI-B ( rat homolog of TR3/Nur77 ) response element</dna> ( <dna>NBRE</dna> ) provided evidence that <protein>Tax</protein> -mediated transactivation resulted in the induction of a functional protein ."}675{"id": "674", "text": "Cotransfection assays with the TR3/nur77 promoter sequence or the NBRE binding motif together with a series of Tax mutants have shown that Tax -induced TR3/nur77 expression is mediated by CREB/ATF-related transcription factors .", "annotated_text": "Cotransfection assays with the <dna>TR3/nur77 promoter sequence</dna> or the <dna>NBRE</dna> binding motif together with a series of <protein>Tax</protein> mutants have shown that <protein>Tax</protein> -induced <protein>TR3/nur77</protein> expression is mediated by <protein>CREB/ATF-related transcription factors</protein> ."}676{"id": "675", "text": "Negative regulation of the heat shock transcriptional response by HSBP1 .", "annotated_text": "Negative regulation of the heat shock transcriptional response by <protein>HSBP1</protein> ."}677{"id": "676", "text": "In response to stress , heat shock factor 1 ( HSF1 ) acquires rapid DNA binding and transient transcriptional activity while undergoing conformational transition from an inert non-DNA-binding monomer to active functional trimers .", "annotated_text": "In response to stress , <protein>heat shock factor 1</protein> ( <protein>HSF1</protein> ) acquires rapid DNA binding and transient transcriptional activity while undergoing conformational transition from an inert <protein>non-DNA-binding monomer</protein> to active functional trimers ."}678{"id": "677", "text": "Attenuation of the inducible transcriptional response occurs during heat shock or upon recovery at non-stress conditions and involves dissociation of the HSF1 trimer and loss of activity .", "annotated_text": "Attenuation of the inducible transcriptional response occurs during heat shock or upon recovery at non-stress conditions and involves dissociation of the <protein>HSF1 trimer</protein> and loss of activity ."}679{"id": "678", "text": "We have used the hydrophobic repeats of the HSF1 trimerization domain in the yeast two-hybrid protein interaction assay to identify heat shock factor binding protein 1 ( HSBP1 ) , a novel , conserved , 76-amino-acid protein that contains two extended arrays of hydrophobic repeats that interact with the HSF1 heptad repeats .", "annotated_text": "We have used the <protein>hydrophobic repeats</protein> of the <protein>HSF1</protein> trimerization domain in the yeast two-hybrid protein interaction assay to identify <protein>heat shock factor binding protein 1</protein> ( <protein>HSBP1</protein> ) , a novel , conserved , <protein>76-amino-acid protein</protein> that contains two extended arrays of <protein>hydrophobic repeats</protein> that interact with the <protein>HSF1 heptad repeats</protein> ."}680{"id": "679", "text": "HSBP1 is nuclear-localized and interacts in vivo with the active trimeric state of HSF1 that appears during heat shock .", "annotated_text": "<protein>HSBP1</protein> is nuclear-localized and interacts in vivo with the active trimeric state of <protein>HSF1</protein> that appears during heat shock ."}681{"id": "680", "text": "During attenuation of HSF1 to the inert monomer , HSBP1 associates with Hsp70 .", "annotated_text": "During attenuation of <protein>HSF1</protein> to the inert monomer , <protein>HSBP1</protein> associates with Hsp70 ."}682{"id": "681", "text": "HSBP1 negatively affects HSF1 DNA-binding activity , and overexpression of HSBP1 in mammalian cells represses the transactivation activity of HSF1 .", "annotated_text": "<protein>HSBP1</protein> negatively affects <protein>HSF1</protein> DNA-binding activity , and overexpression of <protein>HSBP1</protein> in <cell_type>mammalian cells</cell_type> represses the transactivation activity of <protein>HSF1</protein> ."}683{"id": "682", "text": "To establish a biological role for HSBP1 , the homologous Caenorhabditis elegans protein was overexpressed in body wall muscle cells and was shown to block activation of the heat shock response from a heat shock promoter-reporter construct .", "annotated_text": "To establish a biological role for <protein>HSBP1</protein> , the homologous <protein>Caenorhabditis elegans protein</protein> was overexpressed in <cell_type>body wall muscle cells</cell_type> and was shown to block activation of the heat shock response from a <dna>heat shock promoter-reporter construct</dna> ."}684{"id": "683", "text": "Alteration in the level of HSBP1 expression in C. elegans has severe effects on survival of the animals after thermal and chemical stress , consistent with a role for HSBP1 as a negative regulator of the heat shock response .", "annotated_text": "Alteration in the level of <protein>HSBP1</protein> expression in C. elegans has severe effects on survival of the animals after thermal and chemical stress , consistent with a role for <protein>HSBP1</protein> as a negative regulator of the heat shock response ."}685{"id": "684", "text": "Long-range transcriptional regulation of cytokine gene expression .", "annotated_text": "Long-range transcriptional regulation of cytokine gene expression ."}686{"id": "685", "text": "Most studies on the control of cytokine gene expression have involved the functional analysis of proximal promoters .", "annotated_text": "Most studies on the control of cytokine gene expression have involved the functional analysis of <dna>proximal promoters</dna> ."}687{"id": "686", "text": "Recent work has identified distal elements that mediate long-range cytokine gene regulation and has implicated chromatin reorganization in regulation of cytokine gene loci .", "annotated_text": "Recent work has identified <dna>distal elements</dna> that mediate long-range cytokine gene regulation and has implicated chromatin reorganization in regulation of <dna>cytokine gene loci</dna> ."}688{"id": "687", "text": "These studies have begun to elucidate the basis for cell-specificity and high-level expression of cytokine genes .", "annotated_text": "These studies have begun to elucidate the basis for cell-specificity and high-level expression of <dna>cytokine genes</dna> ."}689{"id": "688", "text": "A signaling complex of Ca2+-calmodulin-dependent protein kinase IV and protein phosphatase 2A [ see comments ]", "annotated_text": "A signaling complex of <protein>Ca2+-calmodulin-dependent protein kinase IV</protein> and <protein>protein phosphatase 2A</protein> [ see comments ]"}690{"id": "689", "text": "Stimulation of T lymphocytes results in a rapid increase in intracellular calcium concentration ( [ Ca2+ ] i ) that parallels the activation of Ca2+-calmodulin-dependent protein kinase IV ( CaMKIV ) , a nuclear enzyme that can phosphorylate and activate the cyclic adenosine monophosphate ( cAMP ) response element-binding protein ( CREB ) .", "annotated_text": "Stimulation of <cell_type>T lymphocytes</cell_type> results in a rapid increase in intracellular calcium concentration ( [ Ca2+ ] i ) that parallels the activation of <protein>Ca2+-calmodulin-dependent protein kinase IV</protein> ( <protein>CaMKIV</protein> ) , a <protein>nuclear enzyme</protein> that can phosphorylate and activate the <protein>cyclic adenosine monophosphate ( cAMP ) response element-binding protein</protein> ( <protein>CREB</protein> ) ."}691{"id": "690", "text": "However , inactivation of CaMKIV occurs despite the sustained increase in [ Ca2+ ] i that is required for T cell activation .", "annotated_text": "However , inactivation of <protein>CaMKIV</protein> occurs despite the sustained increase in [ Ca2+ ] i that is required for T cell activation ."}692{"id": "691", "text": "A stable and stoichiometric complex of CaMKIV with protein serine-threonine phosphatase 2A ( PP2A ) was identified in which PP2A dephosphorylates CaMKIV and functions as a negative regulator of CaMKIV signaling .", "annotated_text": "A stable and stoichiometric complex of <protein>CaMKIV</protein> with <protein>protein serine-threonine phosphatase 2A</protein> ( <protein>PP2A</protein> ) was identified in which <protein>PP2A</protein> dephosphorylates <protein>CaMKIV</protein> and functions as a negative regulator of <protein>CaMKIV</protein> signaling ."}693{"id": "692", "text": "In Jurkat T cells , inhibition of PP2A activity by small t antigen enhanced activation of CREB -mediated transcription by CaMKIV .", "annotated_text": "In <cell_line>Jurkat T cells</cell_line> , inhibition of <protein>PP2A</protein> activity by small t antigen enhanced activation of <protein>CREB</protein> -mediated transcription by <protein>CaMKIV</protein> ."}694{"id": "693", "text": "These findings reveal an intracellular signaling mechanism whereby a protein serine-threonine kinase ( CaMKIV ) is regulated by a tightly associated protein serine-threonine phosphatase ( PP2A ) .", "annotated_text": "These findings reveal an intracellular signaling mechanism whereby a <protein>protein serine-threonine kinase</protein> ( <protein>CaMKIV</protein> ) is regulated by a tightly associated <protein>protein serine-threonine phosphatase</protein> ( <protein>PP2A</protein> ) ."}695{"id": "694", "text": "Hypoxia down-regulates MCP-1 expression : implications for macrophage distribution in tumors .", "annotated_text": "Hypoxia down-regulates <protein>MCP-1</protein> expression : implications for macrophage distribution in tumors ."}696{"id": "695", "text": "Monocyte chemoattractant protein 1 ( MCP-1 ) is likely to contribute to the macrophage infiltrate in human ovarian carcinomas .", "annotated_text": "<protein>Monocyte chemoattractant protein 1</protein> ( <protein>MCP-1</protein> ) is likely to contribute to the <cell_type>macrophage infiltrate</cell_type> in human ovarian carcinomas ."}697{"id": "696", "text": "Although MCP-1 is predominantly expressed by the tumor parenchyma , macrophages accumulate at highest density in necrotic regions , which are associated with low oxygen tensions .", "annotated_text": "Although <protein>MCP-1</protein> is predominantly expressed by the tumor parenchyma , macrophages accumulate at highest density in necrotic regions , which are associated with low oxygen tensions ."}698{"id": "697", "text": "Tumor necrosis factor alpha ( TNF-alpha ) can stimulate MCP-1 production and is also present within ovarian carcinomas .", "annotated_text": "<protein>Tumor necrosis factor alpha</protein> ( <protein>TNF-alpha</protein> ) can stimulate <protein>MCP-1</protein> production and is also present within ovarian carcinomas ."}699{"id": "698", "text": "We have investigated the effect of hypoxia both on MCP-1 expression in ovarian cancer cell lines and monocyte migration .", "annotated_text": "We have investigated the effect of hypoxia both on <protein>MCP-1</protein> expression in <cell_line>ovarian cancer cell lines</cell_line> and monocyte migration ."}700{"id": "699", "text": "Hypoxia down-regulated TNF-alpha-induced MCP-1 mRNA and protein production by ovarian cancer cells .", "annotated_text": "Hypoxia down-regulated <rna>TNF-alpha-induced MCP-1 mRNA</rna> and protein production by <cell_type>ovarian cancer cells</cell_type> ."}701{"id": "700", "text": "The effect was mimicked by cobalt chloride and desferrioxamine , consistent with a specific oxygen-sensing mechanism .", "annotated_text": "The effect was mimicked by cobalt chloride and desferrioxamine , consistent with a specific oxygen-sensing mechanism ."}702{"id": "701", "text": "Unlike antioxidants , hypoxia did not inhibit nuclear factor KB mobilization .", "annotated_text": "Unlike antioxidants , hypoxia did not inhibit nuclear factor KB mobilization ."}703{"id": "702", "text": "Monocyte migration in response to MCP-1 was also diminished under hypoxic conditions .", "annotated_text": "Monocyte migration in response to <protein>MCP-1</protein> was also diminished under hypoxic conditions ."}704{"id": "703", "text": "Down-regulation of MCP-1 expression and the inhibition of monocyte migration are independent effects of hypoxia that may contribute to the distribution of macrophages within ovarian tumors .", "annotated_text": "Down-regulation of <protein>MCP-1</protein> expression and the inhibition of monocyte migration are independent effects of hypoxia that may contribute to the distribution of <cell_type>macrophages</cell_type> within ovarian tumors ."}705{"id": "704", "text": "Activation of nuclear factor kappa B inflammatory bowel disease [ see comments ]", "annotated_text": "Activation of <protein>nuclear factor kappa B</protein> inflammatory bowel disease [ see comments ]"}706{"id": "705", "text": "BACKGROUND : Expression of pro-inflammatory cytokines is increased in the intestinal lamina propria of patients with inflammatory bowel disease ( IBD ) .", "annotated_text": "BACKGROUND : Expression of <protein>pro-inflammatory cytokines</protein> is increased in the intestinal lamina propria of patients with inflammatory bowel disease ( IBD ) ."}707{"id": "706", "text": "Nuclear factor kappa B ( NF kappa B ) controls transcription of inflammation genes .", "annotated_text": "<protein>Nuclear factor kappa B</protein> ( <protein>NF kappa B</protein> ) controls transcription of <dna>inflammation genes</dna> ."}708{"id": "707", "text": "On activation , NF kappa B is rapidly released from its cytoplasmic inhibitor ( I kappa B ) , transmigrates into the nucleus , and binds to DNA response elements in gene promoter regions .", "annotated_text": "On activation , <protein>NF kappa B</protein> is rapidly released from its <protein>cytoplasmic inhibitor</protein> ( <protein>I kappa B</protein> ) , transmigrates into the nucleus , and binds to <dna>DNA response elements</dna> in gene promoter regions ."}709{"id": "708", "text": "AIMS : To investigate whether increased activation of NF kappa B is important in IBD and may be down-regulated by anti-inflammatory treatment .", "annotated_text": "AIMS : To investigate whether increased activation of <protein>NF kappa B</protein> is important in IBD and may be down-regulated by anti-inflammatory treatment ."}710{"id": "709", "text": "METHODS : Activation of NF kappa B was determined by western blot assessment and electrophoretic mobility shift assay in nuclear extracts of colonic biopsy samples as well as lamina propria mononuclear cells .", "annotated_text": "METHODS : Activation of <protein>NF kappa B</protein> was determined by western blot assessment and electrophoretic mobility shift assay in nuclear extracts of colonic biopsy samples as well as <cell_type>lamina propria mononuclear cells</cell_type> ."}711{"id": "710", "text": "RESULTS : Nuclear levels of NF kappa B p65 are increased in lamina propria biopsy specimens from patients with Crohn 's disease in comparison with patients with ulcerative colitis and controls .", "annotated_text": "RESULTS : Nuclear levels of <protein>NF kappa B</protein> <protein>p65</protein> are increased in lamina propria biopsy specimens from patients with Crohn 's disease in comparison with patients with ulcerative colitis and controls ."}712{"id": "711", "text": "Increased activation of NF kappa B was detected in lamina propria mononuclear cells from patients with active IBD .", "annotated_text": "Increased activation of <protein>NF kappa B</protein> was detected in <cell_type>lamina propria mononuclear cells</cell_type> from patients with active IBD ."}713{"id": "712", "text": "Corticosteroids strongly inhibit intestinal NF kappa B activation in IBD in vivo and in vitro by stabilising the cytosolic inhibitor I kappa B alpha against activation induced degradation .", "annotated_text": "Corticosteroids strongly inhibit intestinal <protein>NF kappa B</protein> activation in IBD in vivo and in vitro by stabilising the <protein>cytosolic inhibitor</protein> <protein>I kappa B</protein> alpha against activation induced degradation ."}714{"id": "713", "text": "CONCLUSIONS : In both IBDs , but particularly Crohn 's disease , increased activation of NF kappa B may be involved in the regulation of the inflammatory response .", "annotated_text": "CONCLUSIONS : In both IBDs , but particularly Crohn 's disease , increased activation of <protein>NF kappa B</protein> may be involved in the regulation of the inflammatory response ."}715{"id": "714", "text": "Inhibition of NF kappa B activation may represent a mechanism by which steroids exert an anti-inflammatory effect in IBD", "annotated_text": "Inhibition of <protein>NF kappa B</protein> activation may represent a mechanism by which steroids exert an anti-inflammatory effect in IBD"}716{"id": "715", "text": "Insufficient glycemic control increases nuclear factor-kappa B binding activity in peripheral blood mononuclear cells isolated from patients with type 1 diabetes .", "annotated_text": "Insufficient glycemic control increases <protein>nuclear factor-kappa B</protein> binding activity in <cell_type>peripheral blood mononuclear cells</cell_type> isolated from patients with type 1 diabetes ."}717{"id": "716", "text": "OBJECTIVE : The redox-sensitive transcription factor nuclear factor-kappa B ( NF-kappa B ) is believed to contribute to late diabetic complications .", "annotated_text": "OBJECTIVE : The <protein>redox-sensitive transcription factor nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) is believed to contribute to late diabetic complications ."}718{"id": "717", "text": "It is unknown whether NF-kappa B is influenced by glycemic control .", "annotated_text": "It is unknown whether <protein>NF-kappa B</protein> is influenced by glycemic control ."}719{"id": "718", "text": "RESEARCH DESIGN AND METHODS : To determine whether NF-kappa B is activated in patients with insufficient glycemic control ( HbA1c > 10 % ) , we developed a tissue culture-independent electrophoretic mobility shift assay ( EMSA ) -based semiquantitative detection system that allowed us to determine NF-kappa B activation in ex vivo-isolated peripheral blood mononuclear cells ( PBMCs ) .", "annotated_text": "RESEARCH DESIGN AND METHODS : To determine whether <protein>NF-kappa B</protein> is activated in patients with insufficient glycemic control ( HbA1c > 10 % ) , we developed a tissue culture-independent electrophoretic mobility shift assay ( EMSA ) -based semiquantitative detection system that allowed us to determine <protein>NF-kappa B</protein> activation in ex vivo-isolated <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMCs</cell_type> ) ."}720{"id": "719", "text": "We included 43 patients with type 1 diabetes in this cross-sectional study .", "annotated_text": "We included 43 patients with type 1 diabetes in this cross-sectional study ."}721{"id": "720", "text": "10 of those received the antioxidant thioctic acid ( 600 mg/day p.o. ) for 2 weeks .", "annotated_text": "10 of those received the antioxidant thioctic acid ( 600 mg/day p.o. ) for 2 weeks ."}722{"id": "721", "text": "RESULTS : Monocytes of patients with HbA1c levels > 10 % demonstrated significantly higher NF-kappa B binding activity in an EMSA and a stronger NF-kappa B staining in immunohistochemistry than monocytes of patients with HbA1c levels of 6-8 % .", "annotated_text": "RESULTS : Monocytes of patients with HbA1c levels > 10 % demonstrated significantly higher <protein>NF-kappa B</protein> binding activity in an EMSA and a stronger <protein>NF-kappa B</protein> staining in immunohistochemistry than <cell_type>monocytes</cell_type> of patients with HbA1c levels of 6-8 % ."}723{"id": "722", "text": "The increase in NF-kappa B activation correlated with an increase in plasmatic markers of lipid peroxidation .", "annotated_text": "The increase in <protein>NF-kappa B</protein> activation correlated with an increase in plasmatic markers of lipid peroxidation ."}724{"id": "723", "text": "Treatment with the antioxidant thioctic acid decreased NF-kappa B binding activity .", "annotated_text": "Treatment with the antioxidant thioctic acid decreased <protein>NF-kappa B</protein> binding activity ."}725{"id": "724", "text": "CONCLUSIONS : Hyperglycemia induces activation of the transcription factor NF-kappa B in ex vivo-isolated PBMCs of patients with type 1 diabetes .", "annotated_text": "CONCLUSIONS : Hyperglycemia induces activation of the transcription factor <protein>NF-kappa B</protein> in ex vivo-isolated <cell_type>PBMCs</cell_type> of patients with type 1 diabetes ."}726{"id": "725", "text": "NF-kappa B activation is at least partially dependent on oxidative stress , since the antioxidant thioctic acid significantly lowered the extent of NF-kappa B binding activity .", "annotated_text": "<protein>NF-kappa B</protein> activation is at least partially dependent on oxidative stress , since the antioxidant thioctic acid significantly lowered the extent of <protein>NF-kappa B</protein> binding activity ."}727{"id": "726", "text": "Synergistic activation of MAP kinase ( ERK1/2 ) by erythropoietin and stem cell factor is essential for expanded erythropoiesis .", "annotated_text": "Synergistic activation of <protein>MAP kinase</protein> ( <protein>ERK1/2</protein> ) by <protein>erythropoietin</protein> and <protein>stem cell factor</protein> is essential for expanded erythropoiesis ."}728{"id": "727", "text": "Stem cell factor ( SCF ) and erythropoietin ( EPO ) work synergistically to support erythropoiesis , but the mechanism for this synergism is unknown .", "annotated_text": "<protein>Stem cell factor</protein> ( <protein>SCF</protein> ) and <protein>erythropoietin</protein> ( <protein>EPO</protein> ) work synergistically to support erythropoiesis , but the mechanism for this synergism is unknown ."}729{"id": "728", "text": "By using purified human erythroid colony-forming cells ( ECFC ) , we have found that SCF and EPO synergistically activate MAP kinase ( MAPK , ERK1/2 ) , which correlates with the cell growth and thus may be responsible for the synergistic effects .", "annotated_text": "By using <cell_line>purified human erythroid colony-forming cells</cell_line> ( <cell_line>ECFC</cell_line> ) , we have found that <protein>SCF</protein> and <protein>EPO</protein> synergistically activate <protein>MAP kinase</protein> ( <protein>MAPK</protein> , <protein>ERK1/2</protein> ) , which correlates with the cell growth and thus may be responsible for the synergistic effects ."}730{"id": "729", "text": "Treatment of the cells with PD98059 and wortmannin , inhibitors of MEK and PI-3 kinase , respectively , inhibited the synergistic activation of MAPK and also the cell growth , further supporting this conclusion .", "annotated_text": "Treatment of the cells with PD98059 and wortmannin , inhibitors of <protein>MEK</protein> and <protein>PI-3 kinase</protein> , respectively , inhibited the synergistic activation of <protein>MAPK</protein> and also the cell growth , further supporting this conclusion ."}731{"id": "730", "text": "Wortmannin only inhibits MAPK activation induced by EPO but not that by SCF , suggesting that SCF and EPO may activate MAPK through different pathways , which would facilitate synergy .", "annotated_text": "Wortmannin only inhibits <protein>MAPK</protein> activation induced by <protein>EPO</protein> but not that by <protein>SCF</protein> , suggesting that <protein>SCF</protein> and <protein>EPO</protein> may activate <protein>MAPK</protein> through different pathways , which would facilitate synergy ."}732{"id": "731", "text": "Furthermore , EPO , but not SCF , led to activation of STAT5 , whereas SCF and wortmannin had no effect on the EPO -induced STAT5 activation , suggesting that STAT5 is not involved in the synergistic action of SCF and EPO .", "annotated_text": "Furthermore , <protein>EPO</protein> , but not <protein>SCF</protein> , led to activation of <protein>STAT5</protein> , whereas <protein>SCF</protein> and wortmannin had no effect on the <protein>EPO</protein> -induced <protein>STAT5</protein> activation , suggesting that <protein>STAT5</protein> is not involved in the synergistic action of <protein>SCF</protein> and <protein>EPO</protein> ."}733{"id": "732", "text": "Together , the data suggest that synergistic activation of MAPK by SCF and EPO is essential for expanded erythropoiesis .", "annotated_text": "Together , the data suggest that synergistic activation of <protein>MAPK</protein> by <protein>SCF</protein> and <protein>EPO</protein> is essential for expanded erythropoiesis ."}734{"id": "733", "text": "Copyright 1998 by The American Society of Hematology .", "annotated_text": "Copyright 1998 by The American Society of Hematology ."}735{"id": "734", "text": "The molecular and phenotypic profile of primary central nervous system lymphoma identifies distinct categories of the disease and is consistent with histogenetic derivation from germinal center-related B cells .", "annotated_text": "The molecular and phenotypic profile of primary central nervous system lymphoma identifies distinct categories of the disease and is consistent with histogenetic derivation from <cell_type>germinal center-related B cells</cell_type> ."}736{"id": "735", "text": "Primary central nervous system lymphoma ( PCNSL ) is a major cause of morbidity and mortality among human immunodeficiency virus ( HIV ) -infected individuals .", "annotated_text": "Primary central nervous system lymphoma ( PCNSL ) is a major cause of morbidity and mortality among human immunodeficiency virus ( HIV ) -infected individuals ."}737{"id": "736", "text": "The precise histogenetic derivation and the molecular pathogenesis of PCNSL is poorly understood .", "annotated_text": "The precise histogenetic derivation and the molecular pathogenesis of PCNSL is poorly understood ."}738{"id": "737", "text": "In an attempt to clarify the histogenesis and pathogenesis of these lymphomas , 49 PCNSL ( 26 acquired immunodeficiency syndrome [ AIDS ] -related and 23 AIDS-unrelated ) were analyzed for multiple biologic markers , which are known to bear histogenetic and pathogenetic significance for mature B-cell neoplasms .", "annotated_text": "In an attempt to clarify the histogenesis and pathogenesis of these lymphomas , 49 PCNSL ( 26 acquired immunodeficiency syndrome [ AIDS ] -related and 23 AIDS-unrelated ) were analyzed for multiple biologic markers , which are known to bear histogenetic and pathogenetic significance for mature B-cell neoplasms ."}739{"id": "738", "text": "PCNSL associated frequently ( 50.0 % ) with mutations of BCL-6 5 ' noncoding regions , which are regarded as a marker of B-cell transition through the germinal center ( GC ) .", "annotated_text": "PCNSL associated frequently ( 50.0 % ) with mutations of <dna>BCL-6 5 ' noncoding regions</dna> , which are regarded as a marker of B-cell transition through the germinal center ( GC ) ."}740{"id": "739", "text": "Expression of BCL-6 protein , which is restricted to GC B cells throughout physiologic B-cell maturation , was detected in 100 % AIDS-unrelated PCNSL and in 56.2 % AIDS-related cases .", "annotated_text": "Expression of <protein>BCL-6 protein</protein> , which is restricted to <cell_type>GC B cells</cell_type> throughout physiologic B-cell maturation , was detected in 100 % AIDS-unrelated PCNSL and in 56.2 % AIDS-related cases ."}741{"id": "740", "text": "Notably , among AIDS-related PCNSL , expression of BCL-6 was mutually exclusive with expression of Epstein-Barr virus ( EBV ) -encoded latent membrane protein ( LMP ) -1 and , with few exceptions , also of BCL-2 .", "annotated_text": "Notably , among AIDS-related PCNSL , expression of <protein>BCL-6</protein> was mutually exclusive with expression of <protein>Epstein-Barr virus ( EBV ) -encoded latent membrane protein ( LMP ) -1</protein> and , with few exceptions , also of <protein>BCL-2</protein> ."}742{"id": "741", "text": "All but one PCNSL expressed hMSH2 , which among mature B cells selectively stains GC B cells .", "annotated_text": "All but one PCNSL expressed hMSH2 , which among <cell_type>mature B cells</cell_type> selectively stains <cell_type>GC B cells</cell_type> ."}743{"id": "742", "text": "These data suggest that PCNSL may be frequently related to GC B cells and may be segregated into two major biologic categories based on the expression pattern of BCL-6 , LMP-1 , and BCL-2 .", "annotated_text": "These data suggest that PCNSL may be frequently related to <cell_type>GC B cells</cell_type> and may be segregated into two major biologic categories based on the expression pattern of <protein>BCL-6</protein> , <protein>LMP-1</protein> , and <protein>BCL-2</protein> ."}744{"id": "743", "text": "BCL-6 ( + ) / LMP-1 ( - ) / BCL-2 ( - ) PCNSL occur both in the presence and in the absence of HIV infection and consistently display a large noncleaved cell morphology .", "annotated_text": "<protein>BCL-6</protein> ( + ) / <protein>LMP-1</protein> ( - ) / <protein>BCL-2</protein> ( - ) PCNSL occur both in the presence and in the absence of HIV infection and consistently display a large noncleaved cell morphology ."}745{"id": "744", "text": "Conversely , BCL-6 ( - ) / LMP-1 ( + ) / BCL-2 ( + ) PCNSL are restricted to HIV-infected hosts and are represented by lymphomas with immunoblastic features .", "annotated_text": "Conversely , <protein>BCL-6</protein> ( - ) / <protein>LMP-1</protein> ( + ) / <protein>BCL-2</protein> ( + ) PCNSL are restricted to HIV-infected hosts and are represented by lymphomas with immunoblastic features ."}746{"id": "745", "text": "These data are relevant for the pathogenesis and histogenesis of PCNSL and may be helpful to segregate distinct biologic and prognostic categories of these lymphomas .", "annotated_text": "These data are relevant for the pathogenesis and histogenesis of PCNSL and may be helpful to segregate distinct biologic and prognostic categories of these lymphomas ."}747{"id": "746", "text": "Copyright 1998 by The American Society of Hematology .", "annotated_text": "Copyright 1998 by The American Society of Hematology ."}748{"id": "747", "text": "Antioxidant regulation of phorbol ester-induced adhesion of human Jurkat T-cells to endothelial cells .", "annotated_text": "Antioxidant regulation of phorbol ester-induced adhesion of <cell_line>human Jurkat T-cells</cell_line> to <cell_type>endothelial cells</cell_type> ."}749{"id": "748", "text": "Regulation of adhesion molecule expression and function by reactive oxygen species via specific redox sensitive mechanisms have been reported .", "annotated_text": "Regulation of adhesion molecule expression and function by reactive oxygen species via specific redox sensitive mechanisms have been reported ."}750{"id": "749", "text": "The effects of clinically safe antioxidants in the regulation of adhesion molecule expression in human endothelial cells ( ECV ) , and adherence of human Jurkat T cells to ECV cells were investigated .", "annotated_text": "The effects of clinically safe antioxidants in the regulation of adhesion molecule expression in <cell_type>human endothelial cells</cell_type> ( ECV ) , and adherence of <cell_line>human Jurkat T cells</cell_line> to <cell_type>ECV cells</cell_type> were investigated ."}751{"id": "750", "text": "The thiol antioxidant , alpha-lipoate , at clinically relevant doses down-regulated phorbol 12-myristate 13-acetate ( PMA ) -induced adhesion molecule expression and cell-cell adhesion .", "annotated_text": "The thiol antioxidant , alpha-lipoate , at clinically relevant doses down-regulated phorbol 12-myristate 13-acetate ( PMA ) -induced adhesion molecule expression and cell-cell adhesion ."}752{"id": "751", "text": "Inhibition of PMA-induced ICAM-1 and VCAM-1 expression as well as PMA-induced adhesion of Jurkat T-cells to ECV cells by alpha-lipoate was dose dependent ( 50-250 microM ) .", "annotated_text": "Inhibition of PMA-induced ICAM-1 and VCAM-1 expression as well as PMA-induced adhesion of <cell_line>Jurkat T-cells</cell_line> to <cell_type>ECV cells</cell_type> by alpha-lipoate was dose dependent ( 50-250 microM ) ."}753{"id": "752", "text": "The effect was significant for ICAM-1 ( p < .01 ) and VCAM-1 ( p < .01 ) expression in cells pretreated with 100 microM alpha-lipoate compared to PMA-activated untreated cells .", "annotated_text": "The effect was significant for <protein>ICAM-1</protein> ( p < .01 ) and <protein>VCAM-1</protein> ( p < .01 ) expression in cells pretreated with 100 microM alpha-lipoate compared to <cell_type>PMA-activated untreated cells</cell_type> ."}754{"id": "753", "text": "Inhibition of PMA-induced adhesion molecule expression and cell-cell adhesion was more pronounced when a combination of antioxidants , alpha-lipoate and alpha-tocopherol , were used compared to the use of either of these antioxidant alone .", "annotated_text": "Inhibition of PMA-induced adhesion molecule expression and cell-cell adhesion was more pronounced when a combination of antioxidants , alpha-lipoate and alpha-tocopherol , were used compared to the use of either of these antioxidant alone ."}755{"id": "754", "text": "The regulation of adhesion molecule expression and function by low concentration of antioxidants investigated does not appear to be NF-kappaB regulated or transcription dependent because no change in the mRNA response was observed .", "annotated_text": "The regulation of adhesion molecule expression and function by low concentration of antioxidants investigated does not appear to be <protein>NF-kappaB</protein> regulated or transcription dependent because no change in the mRNA response was observed ."}756{"id": "755", "text": "Protein kinase C ( PKC ) has been suggested to regulate PMA-induced adhesion molecule expression by post-transcriptional stabilization of adhesion molecule mRNA .", "annotated_text": "<protein>Protein kinase C</protein> ( <protein>PKC</protein> ) has been suggested to regulate PMA-induced adhesion molecule expression by post-transcriptional stabilization of <rna>adhesion molecule mRNA</rna> ."}757{"id": "756", "text": "Alpha-lipoate pretreatment did not influence the response of PKC activity to PMA .", "annotated_text": "Alpha-lipoate pretreatment did not influence the response of <protein>PKC</protein> activity to PMA ."}758{"id": "757", "text": "Oxidants are known to be involved in the regulation of cell adhesion processes .", "annotated_text": "Oxidants are known to be involved in the regulation of cell adhesion processes ."}759{"id": "758", "text": "Treatment of ECV cells with PMA induced generation of intracellular oxidants .", "annotated_text": "Treatment of <cell_type>ECV cells</cell_type> with PMA induced generation of intracellular oxidants ."}760{"id": "759", "text": "Alpha-lipoate ( 100 or 250 microM ) treatment decreased PMA-induced generation of intracellular oxidants .", "annotated_text": "Alpha-lipoate ( 100 or 250 microM ) treatment decreased PMA-induced generation of intracellular oxidants ."}761{"id": "760", "text": "The inhibitory effect of low concentration of alpha-lipaote alone or in combination with alpha-tocopherol on agonist-induced adhesion processes observed in this study may be of potential therapeutic value .", "annotated_text": "The inhibitory effect of low concentration of alpha-lipaote alone or in combination with alpha-tocopherol on agonist-induced adhesion processes observed in this study may be of potential therapeutic value ."}762{"id": "761", "text": "Binding of human immunodeficiency virus type 1 to CD4 and CXCR4 receptors differentially regulates expression of inflammatory genes and activates the MEK /ERK signaling pathway .", "annotated_text": "Binding of human immunodeficiency virus type 1 to <protein>CD4 and CXCR4 receptors</protein> differentially regulates expression of <dna>inflammatory genes</dna> and activates the <protein>MEK</protein> /ERK signaling pathway ."}763{"id": "762", "text": "We have previously shown that binding of human immunodeficiency virus type 1 ( HIV-1 ) virions to CD4 receptors stimulates association of Lck with Raf-1 and results in the activation of Raf-1 kinase in a Ras-independent manner .", "annotated_text": "We have previously shown that binding of human immunodeficiency virus type 1 ( HIV-1 ) virions to <protein>CD4 receptors</protein> stimulates association of <protein>Lck</protein> with <protein>Raf-1</protein> and results in the activation of <protein>Raf-1</protein> kinase in a Ras-independent manner ."}764{"id": "763", "text": "In the present study , we demonstrate that HIV-1 envelope glycoproteins of both T-cell-tropic and macrophagetropic strains rapidly activate the ERK/mitogen-activated protein ( MAP ) kinase pathway and the binding of nuclear transcription factors ( AP-1 , NF-kappaB , and C/EBP ) and stimulate expression of cytokine and chemokine genes .", "annotated_text": "In the present study , we demonstrate that <protein>HIV-1 envelope glycoproteins</protein> of both T-cell-tropic and macrophagetropic strains rapidly activate the ERK/mitogen-activated protein ( MAP ) kinase pathway and the binding of <protein>nuclear transcription factors</protein> ( <protein>AP-1</protein> , <protein>NF-kappaB</protein> , and <protein>C/EBP</protein> ) and stimulate expression of <dna>cytokine and chemokine genes</dna> ."}765{"id": "764", "text": "The activation of this signaling pathway requires functional CD4 receptors and is independent of binding to CXCR4 .", "annotated_text": "The activation of this signaling pathway requires functional <protein>CD4 receptors</protein> and is independent of binding to <protein>CXCR4</protein> ."}766{"id": "765", "text": "Binding of the natural ligand stromal cell-derived factor 1 ( SDF-1 ) to CXCR4 , which inhibits entry of T-cell-tropic HIV-1 , activates also the ERK/ MAP kinase pathway .", "annotated_text": "Binding of the natural ligand <protein>stromal cell-derived factor 1</protein> ( <protein>SDF-1</protein> ) to <protein>CXCR4</protein> , which inhibits entry of T-cell-tropic HIV-1 , activates also the ERK/ <protein>MAP kinase</protein> pathway ."}767{"id": "766", "text": "However , SDF-1 did not affect the CD4-mediated expression of cytokine and chemokine genes .", "annotated_text": "However , <protein>SDF-1</protein> did not affect the CD4-mediated expression of <dna>cytokine and chemokine genes</dna> ."}768{"id": "767", "text": "These results provide firm molecular evidence that binding of HIV-1 envelope glycoproteins to CD4 receptor initiates a signaling pathway ( s ) independent of the binding to the chemokine receptor that leads to the aberrant expression of inflammatory genes and may contribute significantly to HIV-1 replication as well as to deregulation of the immune system .", "annotated_text": "These results provide firm molecular evidence that binding of <protein>HIV-1 envelope glycoproteins</protein> to <protein>CD4 receptor</protein> initiates a signaling pathway ( s ) independent of the binding to the <protein>chemokine receptor</protein> that leads to the aberrant expression of <dna>inflammatory genes</dna> and may contribute significantly to HIV-1 replication as well as to deregulation of the immune system ."}769{"id": "768", "text": "Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor .", "annotated_text": "Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the <protein>BCL-6</protein> <protein>transcription factor</protein> ."}770{"id": "769", "text": "The bcl-6 proto-oncogene encodes a POZ/zinc finger transcriptional repressor expressed in germinal center ( GC ) B and T cells and required for GC formation and antibody affinity maturation .", "annotated_text": "The <dna>bcl-6 proto-oncogene</dna> encodes a <protein>POZ/zinc finger transcriptional repressor</protein> expressed in <cell_type>germinal center ( GC ) B and T cells</cell_type> and required for GC formation and antibody affinity maturation ."}771{"id": "770", "text": "Deregulation of bcl-6 expression by chromosomal rearrangements and point mutations of the bcl-6 promoter region are implicated in the pathogenesis of B-cell lymphoma .", "annotated_text": "Deregulation of <dna>bcl-6</dna> expression by chromosomal rearrangements and point mutations of the <dna>bcl-6 promoter region</dna> are implicated in the pathogenesis of B-cell lymphoma ."}772{"id": "771", "text": "The signals regulating bcl-6 expression are not known .", "annotated_text": "The signals regulating <dna>bcl-6</dna> expression are not known ."}773{"id": "772", "text": "Here we show that antigen receptor activation leads to BCL-6 phosphorylation by mitogen-activated protein kinase ( MAPK ) .", "annotated_text": "Here we show that antigen receptor activation leads to <protein>BCL-6</protein> phosphorylation by <protein>mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) ."}774{"id": "773", "text": "Phosphorylation , in turn , targets BCL-6 for rapid degradation by the ubiquitin / proteasome pathway .", "annotated_text": "Phosphorylation , in turn , targets <protein>BCL-6</protein> for rapid degradation by the <protein>ubiquitin</protein> / <protein>proteasome</protein> pathway ."}775{"id": "774", "text": "These findings indicate that BCL-6 expression is directly controlled by the antigen receptor via MAPK activation .", "annotated_text": "These findings indicate that <protein>BCL-6</protein> expression is directly controlled by the antigen receptor via <protein>MAPK</protein> activation ."}776{"id": "775", "text": "This signaling pathway may be crucial for the control of B-cell differentiation and antibody response and has implications for the regulation of other POZ/zinc finger transcription factors in other tissues .", "annotated_text": "This signaling pathway may be crucial for the control of B-cell differentiation and antibody response and has implications for the regulation of other <protein>POZ/zinc finger transcription factors</protein> in other tissues ."}777{"id": "776", "text": "Glucocorticoid receptors are differentially expressed in the cells and tissues of the immune system .", "annotated_text": "<protein>Glucocorticoid receptors</protein> are differentially expressed in the cells and tissues of the immune system ."}778{"id": "777", "text": "Cytosolic glucocorticoid receptor ( GR ) binding studies on immune tissues demonstrate that the thymus exhibits three to four times higher levels of GR protein than the spleen .", "annotated_text": "<protein>Cytosolic glucocorticoid receptor</protein> ( <protein>GR</protein> ) binding studies on immune tissues demonstrate that the thymus exhibits three to four times higher levels of <protein>GR protein</protein> than the spleen ."}779{"id": "778", "text": "High levels of GR are consistent with the exquisite sensitivity of the thymus to glucocorticoid exposure .", "annotated_text": "High levels of <protein>GR</protein> are consistent with the exquisite sensitivity of the thymus to glucocorticoid exposure ."}780{"id": "779", "text": "Nevertheless , whole cell binding studies reveal similar levels of GR in immature thymic T lymphocytes and more mature , splenic T lymphocytes .", "annotated_text": "Nevertheless , whole cell binding studies reveal similar levels of <protein>GR</protein> in <cell_type>immature thymic T lymphocytes</cell_type> and more mature , <cell_type>splenic T lymphocytes</cell_type> ."}781{"id": "780", "text": "Moreover , whole cell binding techniques indicate that neutrophils ( which represent roughly 30 % of splenic leukocytes ) exhibit higher GR than both T and B lymphocytes , further contradicting results from cytosolic binding studies .", "annotated_text": "Moreover , whole cell binding techniques indicate that <cell_type>neutrophils</cell_type> ( which represent roughly 30 % of <cell_type>splenic leukocytes</cell_type> ) exhibit higher <protein>GR</protein> than both <cell_type>T and B lymphocytes</cell_type> , further contradicting results from cytosolic binding studies ."}782{"id": "781", "text": "To address these inconsistencies , GR protein was assessed in immune cells and tissues using cytosolic radioligand binding .", "annotated_text": "To address these inconsistencies , <protein>GR protein</protein> was assessed in <cell_type>immune cells and tissues</cell_type> using cytosolic radioligand binding ."}783{"id": "782", "text": "Western blot analysis , and immunocytochemistry .", "annotated_text": "Western blot analysis , and immunocytochemistry ."}784{"id": "783", "text": "Consistent with previous cytosolic receptor binding studies on immune tissue homogenates , thymic T cells were found to have higher levels of GR than T cells isolated from the spleen .", "annotated_text": "Consistent with previous cytosolic receptor binding studies on immune tissue homogenates , thymic <cell_type>T cells</cell_type> were found to have higher levels of <protein>GR</protein> than <cell_type>T cells</cell_type> isolated from the spleen ."}785{"id": "784", "text": "In addition , neutrophils were found to have fewer GR than lymphocytes and monocytes .", "annotated_text": "In addition , neutrophils were found to have fewer <protein>GR</protein> than <cell_type>lymphocytes</cell_type> and <cell_type>monocytes</cell_type> ."}786{"id": "785", "text": "These results indicate a meaningful relationship between receptor expression and known sensitivity to glucocorticoids .", "annotated_text": "These results indicate a meaningful relationship between receptor expression and known sensitivity to glucocorticoids ."}787{"id": "786", "text": "Functional replacement of the mouse E2A gene with a human HEB cDNA .", "annotated_text": "Functional replacement of the <dna>mouse E2A gene</dna> with a <dna>human HEB cDNA</dna> ."}788{"id": "787", "text": "The mammalian E2A , HEB , and E2-2 genes encode a unique class of basic helix-loop-helix ( bHLH ) transcription factors that are evolutionarily conserved and essential for embryonic and postnatal development .", "annotated_text": "The <dna>mammalian E2A , HEB , and E2-2 genes</dna> encode a unique class of <protein>basic helix-loop-helix ( bHLH ) transcription factors</protein> that are evolutionarily conserved and essential for embryonic and postnatal development ."}789{"id": "788", "text": "While the structural and functional similarities among the gene products are well demonstrated , it is not clear why deletion of E2A , but not HEB or E2-2 , leads to a complete arrest in B-lymphocyte development .", "annotated_text": "While the structural and functional similarities among the <protein>gene products</protein> are well demonstrated , it is not clear why deletion of <dna>E2A</dna> , but not <dna>HEB</dna> or <dna>E2-2</dna> , leads to a complete arrest in B-lymphocyte development ."}790{"id": "789", "text": "To understand the molecular basis of the functional specificity between E2A and HEB / E2-2 in mammalian development , we generated and tested a panel of E2A knockin mutations including subtle mutations in the E12 and E47 exons and substitution of both E12 and E47 exons with a human HEB cDNA .", "annotated_text": "To understand the molecular basis of the functional specificity between <dna>E2A</dna> and <dna>HEB</dna> / <dna>E2-2</dna> in mammalian development , we generated and tested a panel of <dna>E2A</dna> knockin mutations including subtle mutations in the <dna>E12 and E47 exons</dna> and substitution of both <dna>E12 and E47 exons</dna> with a <dna>human HEB cDNA</dna> ."}791{"id": "790", "text": "We find that the alternatively spliced E12 and E47 bHLH proteins of the E2A gene play similar and additive roles in supporting B lymphopoiesis .", "annotated_text": "We find that the alternatively spliced <protein>E12 and E47 bHLH proteins</protein> of the <dna>E2A gene</dna> play similar and additive roles in supporting <cell_type>B lymphopoiesis</cell_type> ."}792{"id": "791", "text": "Further , we find that HEB driven by the endogenous E2A promoter can functionally replace E2A in supporting B-cell commitment and differentiation toward completion .", "annotated_text": "Further , we find that <dna>HEB</dna> driven by the <dna>endogenous E2A promoter</dna> can functionally replace <dna>E2A</dna> in supporting B-cell commitment and differentiation toward completion ."}793{"id": "792", "text": "Finally , the postnatal lethality associated with E2A disruption is fully rescued by the addition of HEB .", "annotated_text": "Finally , the postnatal lethality associated with <dna>E2A</dna> disruption is fully rescued by the addition of <dna>HEB</dna> ."}794{"id": "793", "text": "This study suggests that the functional divergence among E12 , E47 , and HEB in different cell types is partially defined by the context of gene expression .", "annotated_text": "This study suggests that the functional divergence among <dna>E12</dna> , <dna>E47</dna> , and <dna>HEB</dna> in different cell types is partially defined by the context of gene expression ."}795{"id": "794", "text": "Biased dependency of CD80 versus CD86 in the induction of transcription factors regulating the human IL-2 promoter .", "annotated_text": "Biased dependency of <protein>CD80</protein> versus <protein>CD86</protein> in the induction of <protein>transcription factors</protein> regulating the <dna>human IL-2 promoter</dna> ."}796{"id": "795", "text": "In addition to the signals obtained by ligation of the TCR , T cells need additional , co-stimulatory signals to be activated .", "annotated_text": "In addition to the signals obtained by ligation of the TCR , <cell_type>T cells</cell_type> need additional , co-stimulatory signals to be activated ."}797{"id": "796", "text": "One such co-stimulatory signal is delivered when CD28 on T cells binds to CD80 or CD86 on antigen-presenting cells ( APC ) .", "annotated_text": "One such co-stimulatory signal is delivered when <protein>CD28</protein> on <cell_type>T cells</cell_type> binds to <protein>CD80</protein> or <protein>CD86</protein> on <cell_type>antigen-presenting cells</cell_type> ( <cell_type>APC</cell_type> ) ."}798{"id": "797", "text": "In the present study , we analyzed the ability of CD80 and CD86 to co-stimulate human T cells activated by superantigen .", "annotated_text": "In the present study , we analyzed the ability of <protein>CD80</protein> and <protein>CD86</protein> to <cell_type>co-stimulate human T cells</cell_type> activated by superantigen ."}799{"id": "798", "text": "Using the Raji B cell lymphoma , which express similar levels of CD80 and CD86 , it was found that T cell proliferation was mainly co-stimulated by CD80 .", "annotated_text": "Using the <cell_line>Raji B cell lymphoma</cell_line> , which express similar levels of <protein>CD80</protein> and <protein>CD86</protein> , it was found that T cell proliferation was mainly co-stimulated by <protein>CD80</protein> ."}800{"id": "799", "text": "To further characterize the consequences of this biased co-stimulatory dependency , we employed a well-defined system of transfected CHO cells expressing human MHC class II together with CD80 , CD86 or CD80 and CD86 .", "annotated_text": "To further characterize the consequences of this biased co-stimulatory dependency , we employed a well-defined system of transfected <cell_line>CHO cells</cell_line> expressing <protein>human MHC class II</protein> together with <protein>CD80</protein> , <protein>CD86</protein> or <protein>CD80</protein> and <protein>CD86</protein> ."}801{"id": "800", "text": "Proliferation of freshly prepared CD4+ T cells required the presence of either CD80 or CD86 .", "annotated_text": "Proliferation of freshly prepared <cell_type>CD4+ T cells</cell_type> required the presence of either <protein>CD80</protein> or <protein>CD86</protein> ."}802{"id": "801", "text": "However , IL-2 production reached only suboptimal levels in the presence of CD86 but optimal levels with CD80 .", "annotated_text": "However , <protein>IL-2</protein> production reached only suboptimal levels in the presence of <protein>CD86</protein> but optimal levels with <protein>CD80</protein> ."}803{"id": "802", "text": "To analyze IL-2 transcriptional activity in CD80 and CD86 co-stimulated T cells we used Jurkat T cells transfected with luciferase reporter gene constructs .", "annotated_text": "To analyze <protein>IL-2</protein> transcriptional activity in <protein>CD80</protein> and <protein>CD86</protein> co-stimulated <cell_type>T cells</cell_type> we used <cell_line>Jurkat T cells</cell_line> transfected with <dna>luciferase reporter gene constructs</dna> ."}804{"id": "803", "text": "CD80 induced higher levels of IL-2 promoter -enhancer activity compared to CD86 .", "annotated_text": "<protein>CD80</protein> induced higher levels of <dna>IL-2 promoter</dna> -enhancer activity compared to <protein>CD86</protein> ."}805{"id": "804", "text": "Furthermore , the activity of transcription factors regulating the IL-2 promoter-enhancer region including activation protein-1 , CD28 response element and nuclear factor kappaB were 4-8 times higher after CD80 compared to CD86 ligation .", "annotated_text": "Furthermore , the activity of <protein>transcription factors</protein> regulating the <dna>IL-2 promoter-enhancer region</dna> including <protein>activation protein-1</protein> , <dna>CD28 response element</dna> and <protein>nuclear factor kappaB</protein> were 4-8 times higher after <protein>CD80</protein> compared to <protein>CD86</protein> ligation ."}806{"id": "805", "text": "Our results suggest that the eventual appearance of CD80 on recently activated CD86+ APC is important for the superinduction of IL-2 production and to support vigorous T cell proliferation .", "annotated_text": "Our results suggest that the eventual appearance of <protein>CD80</protein> on recently activated <cell_type>CD86+ APC</cell_type> is important for the superinduction of <protein>IL-2</protein> production and to support vigorous T cell proliferation ."}807{"id": "806", "text": "Duplication of the DR3 gene on human chromosome 1p36 and its deletion in human neuroblastoma .", "annotated_text": "Duplication of the <dna>DR3 gene</dna> on <dna>human chromosome 1p36</dna> and its deletion in <cell_type>human neuroblastoma</cell_type> ."}808{"id": "807", "text": "The human DR3 gene , whose product is also known as Wsl-1/APO-3/TRAMP/LARD , encodes a tumor necrosis factor-related receptor that is expressed primarily on the surface of thymocytes and lymphocytes .", "annotated_text": "The <dna>human DR3 gene</dna> , whose product is also known as <protein>Wsl-1/APO-3/TRAMP/LARD</protein> , encodes a <protein>tumor necrosis factor-related receptor</protein> that is expressed primarily on the surface of <cell_type>thymocytes</cell_type> and <cell_type>lymphocytes</cell_type> ."}809{"id": "808", "text": "DR3 is capable of inducing both NF-kappa B activation and apoptosis when overexpressed in mammalian cells , although its ligand has not yet been identified .", "annotated_text": "<protein>DR3</protein> is capable of inducing both <protein>NF-kappa B</protein> activation and apoptosis when overexpressed in <cell_type>mammalian cells</cell_type> , although its ligand has not yet been identified ."}810{"id": "809", "text": "We report here that the DR3 gene locus is tandemly duplicated on human chromosome band 1p36.2-p36.3 and that these genes are hemizygously deleted and/or translocated to another chromosome in neuroblastoma ( NB ) cell lines with amplified MYCN .", "annotated_text": "We report here that the <dna>DR3 gene locus</dna> is tandemly duplicated on <dna>human chromosome band 1p36.2-p36.3</dna> and that these genes are hemizygously deleted and/or translocated to another chromosome in <cell_line>neuroblastoma ( NB ) cell lines</cell_line> with amplified MYCN ."}811{"id": "810", "text": "Duplication of at least a portion of the DR3 gene , including the extracellular and transmembrane regions but not the cytoplasmic domain , was demonstrated by both fluorescence in situ hybridization and genomic Southern blotting .", "annotated_text": "Duplication of at least a portion of the <dna>DR3 gene</dna> , including the <protein>extracellular and transmembrane regions</protein> but not the <protein>cytoplasmic domain</protein> , was demonstrated by both fluorescence in situ hybridization and genomic Southern blotting ."}812{"id": "811", "text": "In most NB cell lines , both the DR3 and the DR3L sequences are simultaneously deleted and/or translocated to another chromosome .", "annotated_text": "In most <cell_line>NB cell lines</cell_line> , both the <dna>DR3 and the DR3L sequences</dna> are simultaneously deleted and/or translocated to another <dna>chromosome</dna> ."}813{"id": "812", "text": "Finally , DR3/ Wsl-1 protein expression is quite variable among these NB cell lines , with very low or undetectable levels in 7 of 17 NB cell lines", "annotated_text": "Finally , <protein>DR3/ Wsl-1 protein</protein> expression is quite variable among these <cell_line>NB cell lines</cell_line> , with very low or undetectable levels in 7 of 17 <cell_line>NB cell lines</cell_line>"}814{"id": "813", "text": "Differential protection of normal and malignant human myeloid progenitors ( CFU-GM ) from Ara-C toxicity using cycloheximide .", "annotated_text": "Differential protection of <cell_type>normal and malignant human myeloid progenitors</cell_type> ( <cell_type>CFU-GM</cell_type> ) from Ara-C toxicity using cycloheximide ."}815{"id": "814", "text": "Cycloheximide , a reversible protein synthesis inhibitor , is thought to block DNA replication in normal cells by preventing synthesis of a labile protein .", "annotated_text": "Cycloheximide , a reversible protein synthesis inhibitor , is thought to block DNA replication in <cell_type>normal cells</cell_type> by preventing synthesis of a <protein>labile protein</protein> ."}816{"id": "815", "text": "In animal systems , cycloheximide protects normal cells from cytotoxic S-phase specific agents , such as cytosine arabinoside ( Ara-C ) .", "annotated_text": "In animal systems , cycloheximide protects <cell_type>normal cells</cell_type> from cytotoxic S-phase specific agents , such as cytosine arabinoside ( Ara-C ) ."}817{"id": "816", "text": "Malignant cells appear not to be susceptible to cycloheximide-induced cycle arrest and , subsequently , may not be protected from Ara-C cytotoxicity .", "annotated_text": "<cell_type>Malignant cells</cell_type> appear not to be susceptible to cycloheximide-induced cycle arrest and , subsequently , may not be protected from Ara-C cytotoxicity ."}818{"id": "817", "text": "The effect of cycloheximide on granulocyte/macrophage progenitors ( CFU-GM ) after in vitro Ara-C exposure was examined using normal human bone marrow , malignant progenitors from patients with chronic myelogenous leukemia ( CML ) , and clonogenic cells from the human acute nonlymphocytic leukemia cell lines HL-60 and KG-1 .", "annotated_text": "The effect of cycloheximide on <cell_type>granulocyte/macrophage progenitors</cell_type> ( <cell_type>CFU-GM</cell_type> ) after in vitro Ara-C exposure was examined using normal human bone marrow , <cell_type>malignant progenitors</cell_type> from patients with chronic myelogenous leukemia ( CML ) , and <cell_line>clonogenic cells</cell_line> from the <cell_line>human acute nonlymphocytic leukemia cell lines HL-60 and KG-1</cell_line> ."}819{"id": "818", "text": "Mononuclear or clonogenic cells were incubated for one hour with cycloheximide , followed by the addition , for three or 17 hours , of Ara-C before being plated in a methylcellulose culture system .", "annotated_text": "<cell_line>Mononuclear or clonogenic cells</cell_line> were incubated for one hour with cycloheximide , followed by the addition , for three or 17 hours , of Ara-C before being plated in a methylcellulose culture system ."}820{"id": "819", "text": "CFU-GM survival was significantly increase if normal cells were treated with cycloheximide before Ara-C exposure .", "annotated_text": "CFU-GM survival was significantly increase if normal cells were treated with cycloheximide before Ara-C exposure ."}821{"id": "820", "text": "Similar cycloheximide pretreatment of CML progenitors and clonogenic HL-60 and KG-1 cells failed to protect CFU-GM from Ara-C-induced cytotoxicity .", "annotated_text": "Similar cycloheximide pretreatment of <cell_type>CML progenitors</cell_type> and <cell_line>clonogenic HL-60 and KG-1 cells</cell_line> failed to protect <cell_type>CFU-GM</cell_type> from Ara-C-induced cytotoxicity ."}822{"id": "821", "text": "Primary cortisol resistance accompanied by a reduction in glucocorticoid receptors in two members of the same family .", "annotated_text": "Primary cortisol resistance accompanied by a reduction in <protein>glucocorticoid receptors</protein> in two members of the same family ."}823{"id": "822", "text": "This report describes studies of a man suspected of having primary cortisol resistance .", "annotated_text": "This report describes studies of a man suspected of having primary cortisol resistance ."}824{"id": "823", "text": "This conclusion is based on his high plasma cortisol levels and high 24-h urinary 17-hydroxycorticosteroid and cortisol excretion , plus the fact that he had no manifestations of Cushing 's syndrome .", "annotated_text": "This conclusion is based on his high plasma cortisol levels and high 24-h urinary 17-hydroxycorticosteroid and cortisol excretion , plus the fact that he had no manifestations of Cushing 's syndrome ."}825{"id": "824", "text": "Among family members tested , his mother also had hypercortisolemia .", "annotated_text": "Among family members tested , his mother also had hypercortisolemia ."}826{"id": "825", "text": "Both mother and son had high levels of unbound plasma cortisol , but their plasma ACTH concentrations were within the normal range .", "annotated_text": "Both mother and son had high levels of unbound plasma cortisol , but their plasma ACTH concentrations were within the normal range ."}827{"id": "826", "text": "Both were partially resistant to dexamethasone adrenal suppression , and both had mild hypertension without hypokalemia .", "annotated_text": "Both were partially resistant to dexamethasone adrenal suppression , and both had mild hypertension without hypokalemia ."}828{"id": "827", "text": "To study this apparent end-organ resistance to cortisol , we examined the glucocorticoid receptors in peripheral mononuclear cells .", "annotated_text": "To study this apparent end-organ resistance to cortisol , we examined the <protein>glucocorticoid receptors</protein> in <cell_type>peripheral mononuclear cells</cell_type> ."}829{"id": "828", "text": "Using whole cell assays , glucocorticoid receptors in both patients were found to have reduced total binding capacity .", "annotated_text": "Using whole cell assays , <protein>glucocorticoid receptors</protein> in both patients were found to have reduced total binding capacity ."}830{"id": "829", "text": "We conclude that these two patients , members of the same family , have primary cortisol resistance accompanied by a reduced number of glucocorticoid receptors .", "annotated_text": "We conclude that these two patients , members of the same family , have primary cortisol resistance accompanied by a reduced number of <protein>glucocorticoid receptors</protein> ."}831{"id": "830", "text": "[ Glucocorticoid receptors and response to polychemotherapy in acute lymphatic leukemia ]", "annotated_text": "[ <protein>Glucocorticoid receptors</protein> and response to polychemotherapy in acute lymphatic leukemia ]"}832{"id": "831", "text": "Glucocorticoid receptor ( GR ) levels were quantified in leukemic blasts from peripheral blood of 86 patients with acute lymphoblastic leukemia .", "annotated_text": "<protein>Glucocorticoid receptor</protein> ( <protein>GR</protein> ) levels were quantified in <cell_type>leukemic blasts</cell_type> from peripheral blood of 86 patients with acute lymphoblastic leukemia ."}833{"id": "832", "text": "The subsequent achievement of complete remission after combination chemotherapy was correlated with high receptor levels .", "annotated_text": "The subsequent achievement of complete remission after combination chemotherapy was correlated with high receptor levels ."}834{"id": "833", "text": "Forty-seven of 50 patients with leukemic cells containing more than 6 , 000 receptor sites and 22 of 36 patients with cells containing less than 6 , 000 receptor sites achieved remission .", "annotated_text": "Forty-seven of 50 patients with <cell_type>leukemic cells</cell_type> containing more than 6 , 000 receptor sites and 22 of 36 patients with cells containing less than 6 , 000 receptor sites achieved remission ."}835{"id": "834", "text": "The study of glucocorticoid receptors in leukemic cells may predict response to combination chemotherapy in patients with acute lymphoblastic leukemia .", "annotated_text": "The study of <protein>glucocorticoid receptors</protein> in <cell_type>leukemic cells</cell_type> may predict response to combination chemotherapy in patients with acute lymphoblastic leukemia ."}836{"id": "835", "text": "Specific uptake of 1 , 25-dihydroxycholecalciferol by human chronic myeloid leukemia cells .", "annotated_text": "Specific uptake of 1 , 25-dihydroxycholecalciferol by <cell_type>human chronic myeloid leukemia cells</cell_type> ."}837{"id": "836", "text": "We have examined mononuclear cell preparations from patients with chronic myeloid leukemia [ CML ] for binding of and response to 1 , 25-dihydroxycholecalciferol [ 1 , 25- ( OH ) 2D3 ] .", "annotated_text": "We have examined <cell_line>mononuclear cell preparations</cell_line> from patients with chronic myeloid leukemia [ CML ] for binding of and response to 1 , 25-dihydroxycholecalciferol [ 1 , 25- ( OH ) 2D3 ] ."}838{"id": "837", "text": "Whole cells specifically took up [ 3H ] -1 , 25- ( OH ) 2D3 with high affinity ( Kd 3.6 X 10 ( -11 ) M ) and low capacity .", "annotated_text": "Whole cells specifically took up [ 3H ] -1 , 25- ( OH ) 2D3 with high affinity ( Kd 3.6 X 10 ( -11 ) M ) and low capacity ."}839{"id": "838", "text": "Subcellular fractionation of labeled cells showed that binding was restricted to cytosols and nuclei .", "annotated_text": "Subcellular fractionation of <cell_line>labeled cells</cell_line> showed that binding was restricted to cytosols and nuclei ."}840{"id": "839", "text": "Sucrose gradient centrifugation of cells preincubated with [ 3H ] -1 , 25- ( OH ) 2D3 revealed a single 3.6S peak which was totally displaced with 100-fold excess nonradioactive hormone .", "annotated_text": "Sucrose gradient centrifugation of cells preincubated with [ 3H ] -1 , 25- ( OH ) 2D3 revealed a single 3.6S peak which was totally displaced with 100-fold excess nonradioactive hormone ."}841{"id": "840", "text": "However , we were unable to demonstrate specific binding of 1 , 25- ( OH ) 2D3 by postlabeling standard cytosol preparations .", "annotated_text": "However , we were unable to demonstrate specific binding of 1 , 25- ( OH ) 2D3 by postlabeling standard cytosol preparations ."}842{"id": "841", "text": "In addition , cytosols prepared from a mixture of CML cells and 1 , 25- ( OH ) 2D3 receptor-positive T47D ( human breast cancer ) cells had less than 10 % of the binding measured in T47D cytosol alone .", "annotated_text": "In addition , cytosols prepared from a mixture of <cell_line>CML cells</cell_line> and <cell_line>1 , 25- ( OH ) 2D3 receptor-positive T47D</cell_line> ( human breast cancer ) cells had less than 10 % of the binding measured in <cell_line>T47D</cell_line> cytosol alone ."}843{"id": "842", "text": "However , the levels of binding in T47D cytosols were not reduced if the receptors were occupied with [ 3H ] -1 , 25- ( OH ) 2D3 prior to the addition of the CML cytosols .", "annotated_text": "However , the levels of binding in <cell_line>T47D</cell_line> cytosols were not reduced if the receptors were occupied with [ 3H ] -1 , 25- ( OH ) 2D3 prior to the addition of the <cell_line>CML</cell_line> cytosols ."}844{"id": "843", "text": "Thus , CML cells appear to contain both the receptor for 1 , 25- ( OH ) 2D3 and an unknown substance which prevents its detection following the preparation of cytosol .", "annotated_text": "Thus , <cell_line>CML cells</cell_line> appear to contain both the receptor for 1 , 25- ( OH ) 2D3 and an unknown substance which prevents its detection following the preparation of cytosol ."}845{"id": "844", "text": "Cells from patients with CML in the chronic phase specifically bound more 1 , 25- ( OH ) 2D3 [ 18.0 +/- 3.2 ( S.E. ) fmol/10 ( 7 ) cells ] than did those in acute myeloid transformation [ 7.2 +/- 1.5 ] or than did cells from patients with acute myeloid leukemia [ 2.6 +/- 0.8 ] .", "annotated_text": "Cells from patients with CML in the chronic phase specifically bound more 1 , 25- ( OH ) 2D3 [ 18.0 +/- 3.2 ( S.E. ) fmol/10 ( 7 ) cells ] than did those in acute myeloid transformation [ 7.2 +/- 1.5 ] or than did cells from patients with acute myeloid leukemia [ 2.6 +/- 0.8 ] ."}846{"id": "845", "text": "Only cells from the first group of patients responded to the addition of 1 , 25- ( OH ) 2D3 by differentiating along the monocyte-macrophage pathway .", "annotated_text": "Only cells from the first group of patients responded to the addition of 1 , 25- ( OH ) 2D3 by differentiating along the monocyte-macrophage pathway ."}847{"id": "846", "text": "We conclude that the differentiation-induction effect of 1 , 25- ( OH ) 2D3 is likely to depend on adequate levels of receptor and that intact cells rather than cytosol preparations should be studied before cells of a particular tissue are designated as receptor negative .", "annotated_text": "We conclude that the differentiation-induction effect of 1 , 25- ( OH ) 2D3 is likely to depend on adequate levels of receptor and that <cell_type>intact cells</cell_type> rather than cytosol preparations should be studied before cells of a particular tissue are designated as receptor negative ."}848{"id": "847", "text": "Effect of cell cycle position on dexamethasone binding by mouse and human lymphoid cell lines : correlation between an increase in dexamethasone binding during S phase and dexamethasone sensitivity .", "annotated_text": "Effect of cell cycle position on dexamethasone binding by <cell_line>mouse and human lymphoid cell lines</cell_line> : correlation between an increase in dexamethasone binding during S phase and dexamethasone sensitivity ."}849{"id": "848", "text": "We determined the effect of cell cycle position on the amount of dexamethasone that was specifically bound by mouse and human lymphoid cell lines .", "annotated_text": "We determined the effect of cell cycle position on the amount of dexamethasone that was specifically bound by <cell_line>mouse and human lymphoid cell lines</cell_line> ."}850{"id": "849", "text": "Cell lines that were either sensitive or resistant to growth inhibition by dexamethasone were compared .", "annotated_text": "<cell_line>Cell lines</cell_line> that were either sensitive or resistant to growth inhibition by dexamethasone were compared ."}851{"id": "850", "text": "Exponentially growing cells were separated by centrifugal elutriation into fractions that corresponded to different positions in the cell cycle .", "annotated_text": "<cell_type>Exponentially growing cells</cell_type> were separated by centrifugal elutriation into fractions that corresponded to different positions in the cell cycle ."}852{"id": "851", "text": "The cell cycle phase distribution of each fraction was estimated by flow cytometry and autoradiography .", "annotated_text": "The cell cycle phase distribution of each fraction was estimated by flow cytometry and autoradiography ."}853{"id": "852", "text": "The amount of dexamethasone bound per cell in each fraction was measured by a whole cell binding assay .", "annotated_text": "The amount of dexamethasone bound per cell in each fraction was measured by a whole cell binding assay ."}854{"id": "853", "text": "In three dexamethasone-sensitive cell lines ( two mouse and one human ) , we found that the amount of dexamethasone bound per cell increased 2-4-fold between G1 phase and S phase , and then decreased during G2/M phase .", "annotated_text": "In three <cell_line>dexamethasone-sensitive cell lines</cell_line> ( two mouse and one human ) , we found that the amount of dexamethasone bound per cell increased 2-4-fold between G1 phase and S phase , and then decreased during G2/M phase ."}855{"id": "854", "text": "Results were the same when the amount of dexamethasone bound per milligram of cell protein was measured .", "annotated_text": "Results were the same when the amount of dexamethasone bound per milligram of <protein>cell protein</protein> was measured ."}856{"id": "855", "text": "Binding affinity was the same during G1 phase and S phase , but the proportion of bound dexamethasone that translocated to the nucleus was greater during S phase .", "annotated_text": "Binding affinity was the same during G1 phase and S phase , but the proportion of bound dexamethasone that translocated to the nucleus was greater during S phase ."}857{"id": "856", "text": "In contrast , we found that the amount of dexamethasone bound per cell by three dexamethasone-resistant cell lines ( two mouse and one human ) did not increase during S phase .", "annotated_text": "In contrast , we found that the amount of dexamethasone bound per cell by three <cell_line>dexamethasone-resistant cell lines</cell_line> ( two mouse and one human ) did not increase during S phase ."}858{"id": "857", "text": "Our results indicate that cell cycle changes in dexamethasone binding are not simply related to changes in cell protein or cell volume during the cell cycle .", "annotated_text": "Our results indicate that cell cycle changes in dexamethasone binding are not simply related to changes in <protein>cell protein</protein> or cell volume during the cell cycle ."}859{"id": "858", "text": "An increase in dexamethasone binding during S phase may be required for dexamethasone to inhibit cell growth , and a failure of dexamethasone binding to increase during S phase might represent a new mechanism of dexamethasone resistance in lymphoid cells .", "annotated_text": "An increase in dexamethasone binding during S phase may be required for dexamethasone to inhibit cell growth , and a failure of dexamethasone binding to increase during S phase might represent a new mechanism of dexamethasone resistance in <cell_type>lymphoid cells</cell_type> ."}860{"id": "859", "text": "Presence and steroid inducibility of glutamine synthetase in human leukemic cells .", "annotated_text": "Presence and steroid inducibility of <protein>glutamine synthetase</protein> in <cell_type>human leukemic cells</cell_type> ."}861{"id": "860", "text": "Glutamine synthetase ( EC 6.3.1.2 ; GS ) is present in lymphoblasts from patients with acute lymphoblastic leukemia ( ALL ) as well as in normal peripheral blood lymphocytes .", "annotated_text": "<protein>Glutamine synthetase</protein> ( EC 6.3.1.2 ; GS ) is present in <cell_type>lymphoblasts</cell_type> from patients with acute lymphoblastic leukemia ( ALL ) as well as in <cell_type>normal peripheral blood lymphocytes</cell_type> ."}862{"id": "861", "text": "In 16 out of 20 ALL patients studied exposure of the cells to physiological concentrations of dexamethasone in vitro increased enzyme activity above the control levels .", "annotated_text": "In 16 out of 20 ALL patients studied exposure of the cells to physiological concentrations of dexamethasone in vitro increased <protein>enzyme</protein> activity above the control levels ."}863{"id": "862", "text": "The increase was specific for glucocorticoid receptor ligands .", "annotated_text": "The increase was specific for <protein>glucocorticoid receptor</protein> ligands ."}864{"id": "863", "text": "A direct correlation was found between the magnitude of glucocorticoid-mediated increase of GS activity and the cellular levels of specific glucocorticoid receptors assayed in the same cell specimen .", "annotated_text": "A direct correlation was found between the magnitude of glucocorticoid-mediated increase of GS activity and the cellular levels of specific <protein>glucocorticoid receptors</protein> assayed in the same <cell_type>cell specimen</cell_type> ."}865{"id": "864", "text": "Moreover , the basal levels of the enzyme measured in cells prior to exposure to dexamethasone correlated negatively with receptor density .", "annotated_text": "Moreover , the basal levels of the <protein>enzyme</protein> measured in cells prior to exposure to dexamethasone correlated negatively with receptor density ."}866{"id": "865", "text": "It is suggested that the presence of steroid-inducible GS in ALL cells may prove to be a marker for functional receptor sites .", "annotated_text": "It is suggested that the presence of <protein>steroid-inducible GS</protein> in <cell_type>ALL cells</cell_type> may prove to be a marker for <protein>functional receptor sites</protein> ."}867{"id": "866", "text": "Binding of progestins to the glucocorticoid receptor .", "annotated_text": "Binding of progestins to the <protein>glucocorticoid receptor</protein> ."}868{"id": "867", "text": "Correlation to their glucocorticoid-like effects on in vitro functions of human mononuclear leukocytes .", "annotated_text": "Correlation to their glucocorticoid-like effects on in vitro functions of <cell_type>human mononuclear leukocytes</cell_type> ."}869{"id": "868", "text": "A number of physiological and synthetic progestins were tested for their ability to compete with [ 3H ] dexamethasone for the binding to the glucocorticoid receptor of human mononuclear leukocytes and their ability to elicit glucocorticoid-like effects on the same cells .", "annotated_text": "A number of physiological and synthetic progestins were tested for their ability to compete with [ 3H ] dexamethasone for the binding to the <protein>glucocorticoid receptor</protein> of <cell_type>human mononuclear leukocytes</cell_type> and their ability to elicit glucocorticoid-like effects on the same cells ."}870{"id": "869", "text": "As compared to the reference compound dexamethasone ( relative receptor binding affinity defined as 100 % ) , two potent synthetic progestins with a pregnane-type structure , megestrol acetate and medroxyprogesterone acetate , were found to display a considerable binding affinity towards the receptor ( 46 and 42 % , respectively ) .", "annotated_text": "As compared to the reference compound dexamethasone ( relative receptor binding affinity defined as 100 % ) , two potent synthetic progestins with a pregnane-type structure , megestrol acetate and medroxyprogesterone acetate , were found to display a considerable binding affinity towards the receptor ( 46 and 42 % , respectively ) ."}871{"id": "870", "text": "The relative binding affinity of the naturally occurring ligand , cortisol , to the receptor was clearly lower ( 25 % ) .", "annotated_text": "The relative binding affinity of the naturally occurring ligand , cortisol , to the receptor was clearly lower ( 25 % ) ."}872{"id": "871", "text": "The effective binding of medroxyprogesterone acetate to the glucocorticoid receptor was confirmed by direct binding studies utilizing a tritiated derivative of this steroid .", "annotated_text": "The effective binding of medroxyprogesterone acetate to the <protein>glucocorticoid receptor</protein> was confirmed by direct binding studies utilizing a tritiated derivative of this steroid ."}873{"id": "872", "text": "No evidence for the existence of a specific progesterone receptor in human mononuclear leukocytes was obtained as judged by the results of competition experiments where a progesterone receptor-specific ligand [ 3H ] Org 2058 was used .", "annotated_text": "No evidence for the existence of a specific <protein>progesterone receptor</protein> in <cell_type>human mononuclear leukocytes</cell_type> was obtained as judged by the results of competition experiments where a progesterone receptor-specific ligand [ 3H ] Org 2058 was used ."}874{"id": "873", "text": "Medroxyprogesterone acetate and megestrol acetate also induced glucocorticoid-like effects on the lymphocyte functions .", "annotated_text": "Medroxyprogesterone acetate and megestrol acetate also induced glucocorticoid-like effects on the <cell_type>lymphocyte</cell_type> functions ."}875{"id": "874", "text": "These included inhibition of the proliferative responses to the T-cell mitogens concanavalin A and phytohaemagglutinin and an enhanced accumulation of immunoglobulin secreting cells in pokeweed mitogen-stimulated cultures .", "annotated_text": "These included inhibition of the proliferative responses to the <protein>T-cell mitogens</protein> <protein>concanavalin A</protein> and <protein>phytohaemagglutinin</protein> and an enhanced accumulation of <cell_type>immunoglobulin secreting cells</cell_type> in <cell_line>pokeweed mitogen-stimulated cultures</cell_line> ."}876{"id": "875", "text": "The progestin effect appears to be mediated through a radiosensitive ( suppressor ) subpopulation of T lymphocytes .", "annotated_text": "The progestin effect appears to be mediated through a radiosensitive ( suppressor ) subpopulation of <cell_type>T lymphocytes</cell_type> ."}877{"id": "876", "text": "In contrast , the synthetic progestins related structurally to 19-nortestosterone , norethisterone and d-norgestrel , were virtually devoid of binding affinity towards the glucocorticoid receptor nor did they measurably influence the in vitro lymphocyte functions .", "annotated_text": "In contrast , the synthetic progestins related structurally to 19-nortestosterone , norethisterone and d-norgestrel , were virtually devoid of binding affinity towards the <protein>glucocorticoid receptor</protein> nor did they measurably influence the in vitro <cell_type>lymphocyte</cell_type> functions ."}878{"id": "877", "text": "These studies demonstrate that certain progestins in common clinical use probably possess inherent glucocorticoid activity and suggest that side effects attributable to this character ( e.g. suppression of the pituitary-adrenal axis ) might be expected when these compounds are used in pharmacological doses .", "annotated_text": "These studies demonstrate that certain progestins in common clinical use probably possess inherent glucocorticoid activity and suggest that side effects attributable to this character ( e.g. suppression of the pituitary-adrenal axis ) might be expected when these compounds are used in pharmacological doses ."}879{"id": "878", "text": "Metabolic and ultrastructural aspects of the in vitro lysis of chronic lymphocytic leukemia cells by glucocorticoids .", "annotated_text": "Metabolic and ultrastructural aspects of the in vitro lysis of <cell_type>chronic lymphocytic leukemia cells</cell_type> by glucocorticoids ."}880{"id": "879", "text": "Human chronic lymphocytic leukemia ( CLL ) cells like prothymocytes and immunoactivated T-lymphocytes are readily lysed in vitro by pharmacological concentrations of glucocorticoids such as cortisol , whereas peripheral blood lymphocytes and thymocytes are unaffected by the hormone .", "annotated_text": "<cell_type>Human chronic lymphocytic leukemia ( CLL ) cells</cell_type> like <cell_type>prothymocytes</cell_type> and <cell_type>immunoactivated T-lymphocytes</cell_type> are readily lysed in vitro by pharmacological concentrations of glucocorticoids such as cortisol , whereas <cell_type>peripheral blood lymphocytes</cell_type> and <cell_type>thymocytes</cell_type> are unaffected by the <protein>hormone</protein> ."}881{"id": "880", "text": "In this study , metabolic and ultrastructural aspects of the cortisol-induced killing process of CLL cells are recorded .", "annotated_text": "In this study , metabolic and ultrastructural aspects of the cortisol-induced killing process of <cell_type>CLL cells</cell_type> are recorded ."}882{"id": "881", "text": "In vitro lysis was found to be temperature dependent and was detected only after 6 to 8 hr incubation with cortisol by means of the trypan blue exclusion test .", "annotated_text": "In vitro lysis was found to be temperature dependent and was detected only after 6 to 8 hr incubation with cortisol by means of the trypan blue exclusion test ."}883{"id": "882", "text": "However , 30 min of incubation with cortisol at either 37 degrees or 4 degrees followed by the removal of the hormone was still sufficient to induce the lytic process .", "annotated_text": "However , 30 min of incubation with cortisol at either 37 degrees or 4 degrees followed by the removal of the <protein>hormone</protein> was still sufficient to induce the lytic process ."}884{"id": "883", "text": "Ultrastructural studies demonstrated sequential changes in the cytoplasm , including swelling of mitochondria and cytoplasmic decompartmentalization , followed by loss of surface microvilli with the appearance of `` holes '' in the cell membrane , and subsequent condensation of nuclear chromatin .", "annotated_text": "Ultrastructural studies demonstrated sequential changes in the cytoplasm , including swelling of mitochondria and cytoplasmic decompartmentalization , followed by loss of surface microvilli with the appearance of `` holes '' in the cell membrane , and subsequent condensation of <dna>nuclear chromatin</dna> ."}885{"id": "884", "text": "The large holes in the membrane appearing after 6 hr of incubation with the hormone may be the cause for the penetration of the viable stain into the dead cells , as seen by light microscopy .", "annotated_text": "The large holes in the membrane appearing after 6 hr of incubation with the <protein>hormone</protein> may be the cause for the penetration of the viable stain into the <cell_type>dead cells</cell_type> , as seen by light microscopy ."}886{"id": "885", "text": "Addition of metabolic inhibitors including actinomycin D , puromycin , and cycloheximide following administration of cortisol resulted in inhibition of the cell lysis .", "annotated_text": "Addition of metabolic inhibitors including actinomycin D , puromycin , and cycloheximide following administration of cortisol resulted in inhibition of the cell lysis ."}887{"id": "886", "text": "An excess of an antagonist such as cortexolone was found to inhibit the cortisol-induced cytolysis of the CLL cells .", "annotated_text": "An excess of an antagonist such as cortexolone was found to inhibit the cortisol-induced cytolysis of the <cell_line>CLL cells</cell_line> ."}888{"id": "887", "text": "It is suggested that the glucocorticoid-induced lysis of human CLL cells is similar to the phenomenon observed in rat or murine lymphocytes and is mediated by interaction of the steroid molecule with the cytoplasmic receptor .", "annotated_text": "It is suggested that the glucocorticoid-induced lysis of <cell_line>human CLL cells</cell_line> is similar to the phenomenon observed in <cell_type>rat or murine lymphocytes</cell_type> and is mediated by interaction of the steroid molecule with the <protein>cytoplasmic receptor</protein> ."}889{"id": "888", "text": "The resulting complex appears to activate specific gene ( s ) the products of which eventually cause cytolysis .", "annotated_text": "The resulting complex appears to activate specific <dna>gene</dna> ( s ) the products of which eventually cause cytolysis ."}890{"id": "889", "text": "Glucocorticoid receptors in lymphoid tumors .", "annotated_text": "<protein>Glucocorticoid receptors</protein> in lymphoid tumors ."}891{"id": "890", "text": "There is a range of levels of glucocorticoid receptor numbers seen in the various subclasses of acute lymphatic leukemia ( ALL ) .", "annotated_text": "There is a range of levels of <protein>glucocorticoid receptor</protein> numbers seen in the various subclasses of acute lymphatic leukemia ( ALL ) ."}892{"id": "891", "text": "This variability can not be explained by the known correlation between active cell proliferation and an increase in the number of receptors , since the tumors with the highest growth fraction ( i.e. , Burkitt 's lymphoma and T-cell leukemia ) tend to have lower average receptor numbers than do tumors with lower growth fractions such as common ALL .", "annotated_text": "This variability can not be explained by the known correlation between active cell proliferation and an increase in the number of receptors , since the tumors with the highest growth fraction ( i.e. , Burkitt 's lymphoma and T-cell leukemia ) tend to have lower average receptor numbers than do tumors with lower growth fractions such as common ALL ."}893{"id": "892", "text": "All clinical specimens from patients with lymphatic leukemia have some measurable level of glucocorticoid receptors ; therefore , the resistance seen in vivo can not be explained by the lack of receptors .", "annotated_text": "All clinical specimens from patients with lymphatic leukemia have some measurable level of <protein>glucocorticoid receptors</protein> ; therefore , the resistance seen in vivo can not be explained by the lack of receptors ."}894{"id": "893", "text": "However , there has been a positive correlation , in our hands , with receptor level and prognosis .", "annotated_text": "However , there has been a positive correlation , in our hands , with receptor level and prognosis ."}895{"id": "894", "text": "On the basis of in vitro models , it is proposed that perhaps the high receptor cell lines ( i.e. , common ALL of childhood ) have relative stability of their genetic material making glucocorticoid-resistant mutations less likely to occur in patients with these cells than in low-receptor cell lines ( i.e. , T-cell leukemia ) .", "annotated_text": "On the basis of in vitro models , it is proposed that perhaps the <cell_line>high receptor cell lines</cell_line> ( i.e. , common ALL of childhood ) have relative stability of their genetic material making glucocorticoid-resistant mutations less likely to occur in patients with these cells than in <cell_line>low-receptor cell lines</cell_line> ( i.e. , T-cell leukemia ) ."}896{"id": "895", "text": "This greater genetic variability in the low-receptor lines could account for the earlier emergence of clinical glucocorticoid resistance in these patients .", "annotated_text": "This greater genetic variability in the <cell_line>low-receptor lines</cell_line> could account for the earlier emergence of clinical glucocorticoid resistance in these patients ."}897{"id": "896", "text": "[ Tumor histology and steroid receptors in breast carcinoma ]", "annotated_text": "[ Tumor histology and <protein>steroid receptors</protein> in breast carcinoma ]"}898{"id": "897", "text": "In Specimens of 115 patients with breast cancer 4 tumorparameters ( tumorsize , tumorboder , nucleargrade , lymphocytic stromal reaction ) 3 features of regional lymphnodes ( sinushistiocytosis , T-cellreaction , lymphnode metastases ) and estrogen and progesteron receptors were determined .", "annotated_text": "In Specimens of 115 patients with breast cancer 4 tumorparameters ( tumorsize , tumorboder , nucleargrade , lymphocytic stromal reaction ) 3 features of regional lymphnodes ( sinushistiocytosis , T-cellreaction , lymphnode metastases ) and <protein>estrogen and progesteron receptors</protein> were determined ."}899{"id": "898", "text": "A strong sinushistiocytosis and T-cellreaction could be verified mainly in metastases in free lymphnodes .", "annotated_text": "A strong sinushistiocytosis and T-cellreaction could be verified mainly in metastases in free lymphnodes ."}900{"id": "899", "text": "The steroid receptor content does not correlate with histological parameters", "annotated_text": "The <protein>steroid receptor</protein> content does not correlate with histological parameters"}901{"id": "900", "text": "Aldosterone-receptor deficiency in pseudohypoaldosteronism .", "annotated_text": "<protein>Aldosterone-receptor</protein> deficiency in pseudohypoaldosteronism ."}902{"id": "901", "text": "Pseudohypoaldosteronism , a syndrome characterized by salt wasting and failure to thrive , usually presents in infancy as high urinary levels of sodium despite hyponatremia , hyperkalemia , hyperreninemia , and elevated aldosterone levels .", "annotated_text": "Pseudohypoaldosteronism , a syndrome characterized by salt wasting and failure to thrive , usually presents in infancy as high urinary levels of sodium despite hyponatremia , hyperkalemia , hyperreninemia , and elevated aldosterone levels ."}903{"id": "902", "text": "We have investigated this syndrome for the possibility of abnormal Type I or `` mineralocorticoid-like '' receptors , which have intrinsic steroid specificity indistinguishable from that of renal mineralocorticoid receptors and are found in many tissues and cells , including mononuclear leukocytes .", "annotated_text": "We have investigated this syndrome for the possibility of <protein>abnormal Type I</protein> or <protein>`` mineralocorticoid-like '' receptors</protein> , which have intrinsic steroid specificity indistinguishable from that of <protein>renal mineralocorticoid receptors</protein> and are found in many tissues and <cell_type>cells</cell_type> , including <cell_type>mononuclear leukocytes</cell_type> ."}904{"id": "903", "text": "We have studied three patients with pseudohypoaldosteronism : the 28-year-old index case in Melbourne ( Patient 1 ) and two siblings in Munich , eight and two years of age ( Patients 2 and 3 ) ; clinically , Patient 3 had a less severe case than his sister .", "annotated_text": "We have studied three patients with pseudohypoaldosteronism : the 28-year-old index case in Melbourne ( Patient 1 ) and two siblings in Munich , eight and two years of age ( Patients 2 and 3 ) ; clinically , Patient 3 had a less severe case than his sister ."}905{"id": "904", "text": "Percoll-separated control monocytes bound [ 3H ] aldosterone with high affinity ( Kd approximately 3 nM ) and limited capacity ( 150 to 600 sites per cell ) .", "annotated_text": "<cell_type>Percoll-separated control monocytes</cell_type> bound [ 3H ] aldosterone with high affinity ( Kd approximately 3 nM ) and limited capacity ( 150 to 600 sites per cell ) ."}906{"id": "905", "text": "On repeated examination , no [ 3H ] aldosterone binding was found in monocytes from Patients 1 and 2 ; in Patient 3 , the levels were 62 sites per cell , more than 2 S.D. below those of the control .", "annotated_text": "On repeated examination , no [ 3H ] aldosterone binding was found in <cell_type>monocytes</cell_type> from Patients 1 and 2 ; in Patient 3 , the levels were 62 sites per cell , more than 2 S.D. below those of the control ."}907{"id": "906", "text": "Levels in the parents of the Munich patients ( first cousins ) were normal .", "annotated_text": "Levels in the parents of the Munich patients ( first cousins ) were normal ."}908{"id": "907", "text": "It appears that pseudohypoaldosteronism is caused by a Type I receptor defect , that the defect may be complete or partial , that transmission may be autosomal recessive , and that the study of patients with pseudohypoaldosteronism may indicate physiologic roles for Type I receptors in nonepithelial tissues .", "annotated_text": "It appears that pseudohypoaldosteronism is caused by a Type I receptor defect , that the defect may be complete or partial , that transmission may be autosomal recessive , and that the study of patients with pseudohypoaldosteronism may indicate physiologic roles for <protein>Type I receptors</protein> in nonepithelial tissues ."}909{"id": "908", "text": "Glucocorticoid inhibition of urokinase-like plasminogen activators in cultured human lymphoblasts .", "annotated_text": "Glucocorticoid inhibition of <protein>urokinase-like plasminogen activators</protein> in <cell_line>cultured human lymphoblasts</cell_line> ."}910{"id": "909", "text": "Two human lymphoblast cell lines , LICR-LON-HMy2 ( HMy2 cells ) and GM4672A cells , are moderately growth inhibited by dexamethasone ( 1 , 4-pregnadien-9-fluoro-16 alpha-methyl-11 beta , 17 alpha , 21-triol-3 , 20-dione ) ( Dex ) .", "annotated_text": "Two <cell_line>human lymphoblast cell lines</cell_line> , <cell_line>LICR-LON-HMy2</cell_line> ( <cell_line>HMy2 cells</cell_line> ) and <cell_line>GM4672A cells</cell_line> , are moderately growth inhibited by dexamethasone ( 1 , 4-pregnadien-9-fluoro-16 alpha-methyl-11 beta , 17 alpha , 21-triol-3 , 20-dione ) ( Dex ) ."}911{"id": "910", "text": "Both cell types secrete a urokinase ( UK ) -like plasminogen activator ( PA ) .", "annotated_text": "Both cell types secrete a <protein>urokinase ( UK ) -like plasminogen activator</protein> ( <protein>PA</protein> ) ."}912{"id": "911", "text": "Treatment of both HMy2 and GM4672A cells with Dex for 1-4 days inhibits extracellular PA activity in a concentration-dependent manner , being half-maximal at approximately 1 X 10 ( -9 ) M .", "annotated_text": "Treatment of both <cell_line>HMy2 and GM4672A cells</cell_line> with Dex for 1-4 days inhibits extracellular <protein>PA</protein> activity in a concentration-dependent manner , being half-maximal at approximately 1 X 10 ( -9 ) M ."}913{"id": "912", "text": "Inhibition of PA in both cell types is specific for active glucocorticoids , and this specificity parallels the ability of various steroids to bind to glucocorticoid receptors .", "annotated_text": "Inhibition of <protein>PA</protein> in both cell types is specific for active glucocorticoids , and this specificity parallels the ability of various steroids to bind to <protein>glucocorticoid receptors</protein> ."}914{"id": "913", "text": "HMy2 cell PA is fully suppressible by Dex , whereas up to one third of the activator expressed by GM4672A cells is resistant to glucocorticoid inhibition .", "annotated_text": "<cell_line>HMy2 cell</cell_line> <protein>PA</protein> is fully suppressible by Dex , whereas up to one third of the activator expressed by <cell_line>GM4672A cells</cell_line> is resistant to glucocorticoid inhibition ."}915{"id": "914", "text": "Mixing experiments using a UK standard and conditioned media from Dex-treated cells suggest an absence of glucocorticoid-inducible inhibitors to UK or plasmin in both cell types .", "annotated_text": "Mixing experiments using a UK standard and conditioned media from <cell_line>Dex-treated cells</cell_line> suggest an absence of <protein>glucocorticoid-inducible inhibitors</protein> to <protein>UK</protein> or <protein>plasmin</protein> in both cell types ."}916{"id": "915", "text": "However , conditioned media from Dex-treated GM4672A cells inhibits a portion of the homologous cellular activator in conditioned media from control GM4672A cells .", "annotated_text": "However , conditioned media from <cell_line>Dex-treated GM4672A cells</cell_line> inhibits a portion of the homologous cellular activator in conditioned media from control <cell_line>GM4672A cells</cell_line> ."}917{"id": "916", "text": "Thus , low levels of glucocorticoid-inducible inhibitors may contribute to , but can not fully account for , Dex inhibition of GM4672A PA activity .", "annotated_text": "Thus , low levels of <protein>glucocorticoid-inducible inhibitors</protein> may contribute to , but can not fully account for , Dex inhibition of <protein>GM4672A PA</protein> activity ."}918{"id": "917", "text": "Glucocorticoid-inducible inhibitors in HMy2 cells are either totally absent or are present at undetectable levels .", "annotated_text": "<protein>Glucocorticoid-inducible inhibitors</protein> in <cell_line>HMy2 cells</cell_line> are either totally absent or are present at undetectable levels ."}919{"id": "918", "text": "Thus , regulation of UK-like PAs in HMy2 and GM4672A cells differs with respect to the extent to which glucocorticoids inhibit constitutively expressed activator levels , as well as the possible contribution of glucocorticoid-inducible inhibitors to the regulatory process in GM4672A cells .", "annotated_text": "Thus , regulation of <protein>UK-like PAs</protein> in <cell_line>HMy2 and GM4672A cells</cell_line> differs with respect to the extent to which glucocorticoids inhibit <protein>constitutively expressed activator</protein> levels , as well as the possible contribution of <protein>glucocorticoid-inducible inhibitors</protein> to the regulatory process in <cell_line>GM4672A cells</cell_line> ."}920{"id": "919", "text": "Characterization of aldosterone binding sites in circulating human mononuclear leukocytes .", "annotated_text": "Characterization of aldosterone binding sites in <cell_type>circulating human mononuclear leukocytes</cell_type> ."}921{"id": "920", "text": "Aldosterone binding sites in human mononuclear leukocytes were characterized after separation of cells from blood by a Percoll gradient .", "annotated_text": "Aldosterone binding sites in <cell_line>human mononuclear leukocytes</cell_line> were characterized after separation of cells from blood by a Percoll gradient ."}922{"id": "921", "text": "After washing and resuspension in RPMI-1640 medium , cells were incubated at 37 degrees C for 1 h with different concentrations of [ 3H ] aldosterone plus a 100-fold concentration of RU-26988 ( 11 alpha , 17 alpha-dihydroxy-17 beta-propynylandrost-1 , 4 , 6-trien-3-one ) , with or without an excess of unlabeled aldosterone .", "annotated_text": "After washing and resuspension in RPMI-1640 medium , cells were incubated at 37 degrees C for 1 h with different concentrations of [ 3H ] aldosterone plus a 100-fold concentration of RU-26988 ( 11 alpha , 17 alpha-dihydroxy-17 beta-propynylandrost-1 , 4 , 6-trien-3-one ) , with or without an excess of unlabeled aldosterone ."}923{"id": "922", "text": "Aldosterone binds to a single class of receptors with an affinity of 2.7 +/- 0.5 nM ( means +/- SD , n = 14 ) and a capacity of 290 +/- 108 sites/cell ( n = 14 ) .", "annotated_text": "Aldosterone binds to a single class of receptors with an affinity of 2.7 +/- 0.5 nM ( means +/- SD , n = 14 ) and a capacity of 290 +/- 108 sites/cell ( n = 14 ) ."}924{"id": "923", "text": "The specificity data show a hierarchy of affinity of desoxycorticosterone = corticosterone = aldosterone greater than hydrocortisone greater than dexamethasone .", "annotated_text": "The specificity data show a hierarchy of affinity of desoxycorticosterone = corticosterone = aldosterone greater than hydrocortisone greater than dexamethasone ."}925{"id": "924", "text": "The results indicate that mononuclear leukocytes could be useful for studying the physiological significance of these mineralocorticoid receptors and their regulation in humans .", "annotated_text": "The results indicate that <cell_type>mononuclear leukocytes</cell_type> could be useful for studying the physiological significance of these <protein>mineralocorticoid receptors</protein> and their regulation in humans ."}926{"id": "925", "text": "Mineralocorticoid and glucocorticoid receptors in circulating mononuclear leukocytes of patients with primary hyperaldosteronism .", "annotated_text": "<protein>Mineralocorticoid and glucocorticoid receptors</protein> in <cell_type>circulating mononuclear leukocytes</cell_type> of patients with primary hyperaldosteronism ."}927{"id": "926", "text": "Mineralocorticoid and glucocorticoid receptors were measured in circulating mononuclear leukocytes in 5 patients affected by Conn 's syndrome ( 3 cases of bilateral adrenal hyperplasia and 2 cases of adenoma plus unilateral hyperplasia ) .", "annotated_text": "<protein>Mineralocorticoid and glucocorticoid receptors</protein> were measured in <cell_type>circulating mononuclear leukocytes</cell_type> in 5 patients affected by Conn 's syndrome ( 3 cases of bilateral adrenal hyperplasia and 2 cases of adenoma plus unilateral hyperplasia ) ."}928{"id": "927", "text": "The number of the binding sites per cell resulted significantly lower ( 189 +/- 114 , mean +/- SD ) , as compared with the normal controls ( 298 +/- 105 ) .", "annotated_text": "The number of the binding sites per cell resulted significantly lower ( 189 +/- 114 , mean +/- SD ) , as compared with the normal controls ( 298 +/- 105 ) ."}929{"id": "928", "text": "The affinity of aldosterone for the receptor was found to be not different than that of healthy control subjects .", "annotated_text": "The affinity of aldosterone for the receptor was found to be not different than that of healthy control subjects ."}930{"id": "929", "text": "The capacity and the affinity of dexamethasone for glucocorticoid receptors ranged in the normal values .", "annotated_text": "The capacity and the affinity of dexamethasone for <protein>glucocorticoid receptors</protein> ranged in the normal values ."}931{"id": "930", "text": "These data suggest a possible down-regulation of mineralocorticoid receptors in humans .", "annotated_text": "These data suggest a possible down-regulation of <protein>mineralocorticoid receptors</protein> in humans ."}932{"id": "931", "text": "Short-term and long-term effects of estrogen on lymphoid tissues and lymphoid cells with some remarks on the significance for carcinogenesis .", "annotated_text": "Short-term and long-term effects of estrogen on lymphoid tissues and <cell_type>lymphoid cells</cell_type> with some remarks on the significance for carcinogenesis ."}933{"id": "932", "text": "Estrogens have long been thought to play a role in regulating the immune system .", "annotated_text": "Estrogens have long been thought to play a role in regulating the immune system ."}934{"id": "933", "text": "The difference in some types of immune responses between males and females is well-known , as is the pronounced thymic involution induced by exogenous estrogens .", "annotated_text": "The difference in some types of immune responses between males and females is well-known , as is the pronounced thymic involution induced by exogenous estrogens ."}935{"id": "934", "text": "Estrogens stimulate some aspects of macrophage activity and , depending on dose and mitogen , inhibit or stimulate lymphocyte proliferative response in vitro .", "annotated_text": "Estrogens stimulate some aspects of <cell_type>macrophage</cell_type> activity and , depending on dose and <protein>mitogen</protein> , inhibit or stimulate lymphocyte proliferative response in vitro ."}936{"id": "935", "text": "Another example is the estrogen effect on the delayed type hypersensitivity response .", "annotated_text": "Another example is the estrogen effect on the delayed type hypersensitivity response ."}937{"id": "936", "text": "A broad review is given of such estrogen effects on lymphoid tissue and immune response .", "annotated_text": "A broad review is given of such estrogen effects on <cell_type>lymphoid tissue</cell_type> and immune response ."}938{"id": "937", "text": "Most of the studies published so far are phenomenological .", "annotated_text": "Most of the studies published so far are phenomenological ."}939{"id": "938", "text": "However , the recent description of estrogen receptors in the thymus and in some lymphocyte subpopulations , as well as a deeper understanding of regulating factors in the immune system , open the possibility of a more detailed understanding of the estrogen mechanism of interference .", "annotated_text": "However , the recent description of <protein>estrogen receptors</protein> in the thymus and in some <cell_line>lymphocyte subpopulations</cell_line> , as well as a deeper understanding of regulating factors in the immune system , open the possibility of a more detailed understanding of the estrogen mechanism of interference ."}940{"id": "939", "text": "Estrogen effects in adults are reversible .", "annotated_text": "Estrogen effects in adults are reversible ."}941{"id": "940", "text": "After treating neonatal mice with the synthetic estrogen diethylstilbestrol ( DES ) , disturbances are induced in lymphocyte populations and lymphocyte functions which are permanent and irreversible .", "annotated_text": "After treating neonatal mice with the synthetic estrogen diethylstilbestrol ( DES ) , disturbances are induced in <cell_line>lymphocyte populations</cell_line> and <cell_type>lymphocyte</cell_type> functions which are permanent and irreversible ."}942{"id": "941", "text": "Lymphocytes from adult , neonatally DES-treated female mice have a reduced mitogen response to ConA and LPS ( T and B cell mitogen ) and the delayed type hypersensitivity response is depressed .", "annotated_text": "<cell_type>Lymphocytes</cell_type> from adult , neonatally DES-treated female mice have a reduced mitogen response to <protein>ConA</protein> and <protein>LPS</protein> ( <protein>T and B cell mitogen</protein> ) and the delayed type hypersensitivity response is depressed ."}943{"id": "942", "text": "A detailed analysis demonstrated a decreased T helper cell population .", "annotated_text": "A detailed analysis demonstrated a decreased <cell_type>T helper cell</cell_type> population ."}944{"id": "943", "text": "The activity of Natural Killer cells is permanently reduced and this functional impairment is related to a decreased number of these cells , in turn determined at the bone marrow level .", "annotated_text": "The activity of <cell_type>Natural Killer cells</cell_type> is permanently reduced and this functional impairment is related to a decreased number of these cells , in turn determined at the bone marrow level ."}945{"id": "944", "text": "The same animals have an increased sensitivity to chemical carcinogens ( methylcholanthrene ) and they spontaneously develop epithelial changes in the uterine cervix which morphologically are similar to adenocarcinoma .", "annotated_text": "The same animals have an increased sensitivity to chemical carcinogens ( methylcholanthrene ) and they spontaneously develop epithelial changes in the uterine cervix which morphologically are similar to adenocarcinoma ."}946{"id": "945", "text": "The association between estrogen-associated malignancy and estrogen effects in lymphocyte functions deserves further study .", "annotated_text": "The association between estrogen-associated malignancy and estrogen effects in <cell_type>lymphocyte</cell_type> functions deserves further study ."}947{"id": "946", "text": "Drugs affecting the hormonal receptors of normal and leukaemic peripheral leucocytes .", "annotated_text": "Drugs affecting the hormonal receptors of <cell_type>normal and leukaemic peripheral leucocytes</cell_type> ."}948{"id": "947", "text": "The authors investigated the behaviour of steroid hormone uptake in leukaemic cells ( CML , CLL , AML , ALL ) , in basal conditions and after incubation with drugs which modify the cellular concentration of cAMP , PGE and PGF .", "annotated_text": "The authors investigated the behaviour of steroid hormone uptake in <cell_type>leukaemic cells</cell_type> ( <cell_line>CML</cell_line> , <cell_line>CLL</cell_line> , <cell_line>AML</cell_line> , <cell_line>ALL</cell_line> ) , in basal conditions and after incubation with drugs which modify the cellular concentration of cAMP , PGE and PGF ."}949{"id": "948", "text": "The results demonstrated the presence in leukaemic cells of an alteration in the incorporation of steroid hormones .", "annotated_text": "The results demonstrated the presence in <cell_type>leukaemic cells</cell_type> of an alteration in the incorporation of steroid hormones ."}950{"id": "949", "text": "This alteration was scarcely modified by incubation with theophylline , which increases cellular concentration of cAMP .", "annotated_text": "This alteration was scarcely modified by incubation with <protein>theophylline</protein> , which increases cellular concentration of cAMP ."}951{"id": "950", "text": "On the other hand , it was moderately counteracted by thioproline and was evidently inhibited by flurbiprofen , which also reduced cellular concentrations of prostaglandins , particularly PGE2 , with the exception of PGF2 which showed a poor response .", "annotated_text": "On the other hand , it was moderately counteracted by thioproline and was evidently inhibited by flurbiprofen , which also reduced cellular concentrations of prostaglandins , particularly PGE2 , with the exception of PGF2 which showed a poor response ."}952{"id": "951", "text": "Differences were observed in the behavior of hormonal uptake of CML , in contrast to that of AML , CLL and ALL peripheral leucocytes .", "annotated_text": "Differences were observed in the behavior of hormonal uptake of <cell_line>CML</cell_line> , in contrast to that of <cell_line>AML , CLL and ALL peripheral leucocytes</cell_line> ."}953{"id": "952", "text": "Human breast cancer and impaired NK cell function .", "annotated_text": "Human breast cancer and impaired <cell_type>NK cell</cell_type> function ."}954{"id": "953", "text": "Recent advances in tumor immunology have led to the discovery of a new lymphoid cell with unique antitumor activity .", "annotated_text": "Recent advances in tumor immunology have led to the discovery of a new <cell_type>lymphoid cell</cell_type> with unique antitumor activity ."}955{"id": "954", "text": "Natural killer ( NK ) cells form an antitumor surveillance system and appear to be vital in preventing tumor growth and metastasis in animal models .", "annotated_text": "<cell_type>Natural killer ( NK ) cells</cell_type> form an antitumor surveillance system and appear to be vital in preventing tumor growth and metastasis in animal models ."}956{"id": "955", "text": "We studied NK activity in patients with benign and malignant breast disease , using a chromium-51 release microtiter cytotoxicity assay with K562 cells as targets .", "annotated_text": "We studied <cell_type>NK</cell_type> activity in patients with benign and malignant breast disease , using a chromium-51 release microtiter cytotoxicity assay with <cell_line>K562 cells</cell_line> as targets ."}957{"id": "956", "text": "Compared with benign controls , patients with malignancies had significantly depressed NK -mediated lysis ( P less than 0.01 ) .", "annotated_text": "Compared with benign controls , patients with malignancies had significantly depressed <cell_type>NK</cell_type> -mediated lysis ( P less than 0.01 ) ."}958{"id": "957", "text": "Furthermore , lysis in those with advanced disease ( stages II , III , and IV ) was significantly less than in those with limited disease ( stage I ) ( P less than 0.01 ) .", "annotated_text": "Furthermore , lysis in those with advanced disease ( stages II , III , and IV ) was significantly less than in those with limited disease ( stage I ) ( P less than 0.01 ) ."}959{"id": "958", "text": "NK activity was not correlated to estrogen or progesterone receptor states .", "annotated_text": "<cell_type>NK</cell_type> activity was not correlated to estrogen or progesterone receptor states ."}960{"id": "959", "text": "Positive correlation of a depressed natural killer activity with the extent of tumor spread supports the concept of an NK cell immune surveillance system in breast cancer and emphasizes its importance in this malignancy .", "annotated_text": "Positive correlation of a depressed natural killer activity with the extent of tumor spread supports the concept of an <cell_type>NK cell</cell_type> immune surveillance system in breast cancer and emphasizes its importance in this malignancy ."}961{"id": "960", "text": "Immunosuppressive effect of serum progesterone during pregnancy depends on the progesterone binding capacity of the lymphocytes .", "annotated_text": "Immunosuppressive effect of serum progesterone during pregnancy depends on the progesterone binding capacity of the <cell_type>lymphocytes</cell_type> ."}962{"id": "961", "text": "Cytotoxic activity and progesterone binding capacity of the lymphocytes , together with serum progesterone concentrations , were determined in women with normal pregnancy or with a clinical diagnosis of threatened abortion or threatened premature labour .", "annotated_text": "Cytotoxic activity and progesterone binding capacity of the <cell_type>lymphocytes</cell_type> , together with serum progesterone concentrations , were determined in women with normal pregnancy or with a clinical diagnosis of threatened abortion or threatened premature labour ."}963{"id": "962", "text": "The lymphocytes of women with threatened abortion or threatened premature labour showed significantly higher cytotoxic activity ( P less than 0.001 ) and significantly lower progesterone binding capacity ( P less than 0.001 ) than did lymphocytes obtained from the healthy pregnant women .", "annotated_text": "The lymphocytes of women with threatened abortion or threatened premature labour showed significantly higher cytotoxic activity ( P less than 0.001 ) and significantly lower progesterone binding capacity ( P less than 0.001 ) than did <cell_type>lymphocytes</cell_type> obtained from the healthy pregnant women ."}964{"id": "963", "text": "Significant inverse correlation was found between progesterone binding capacity and cytotoxic activity of the lymphocytes ( P less than 0.001 ) , but the progesterone concentration of the pregnancy serum appeared to have no influence on the other two parameters .", "annotated_text": "Significant inverse correlation was found between progesterone binding capacity and cytotoxic activity of the <cell_type>lymphocytes</cell_type> ( P less than 0.001 ) , but the progesterone concentration of the pregnancy serum appeared to have no influence on the other two parameters ."}965{"id": "964", "text": "The findings indicate that intact progesterone binding capacity of the lymphocytes is an essential factor for the manifestation of the blocking effect exerted by pregnancy serum on lymphocyte cytotoxicity in vitro .", "annotated_text": "The findings indicate that intact progesterone binding capacity of the <cell_type>lymphocytes</cell_type> is an essential factor for the manifestation of the blocking effect exerted by pregnancy serum on <cell_type>lymphocyte</cell_type> cytotoxicity in vitro ."}966{"id": "965", "text": "Serum sex steroid and peptide hormone concentrations , and endometrial estrogen and progestin receptor levels during administration of human leukocyte interferon .", "annotated_text": "Serum sex steroid and peptide hormone concentrations , and endometrial estrogen and progestin receptor levels during administration of <protein>human leukocyte interferon</protein> ."}967{"id": "966", "text": "Five normally cycling healthy women were given daily subcutaneous injections of human leukocyte interferon ( 3 X 10 ( 6 ) units/day ) from the 3rd through 23rd day of the menstrual cycle , and serum steroid and peptide hormone concentrations monitored at 3-day intervals during the treatment and the preceding control cycle .", "annotated_text": "Five normally cycling healthy women were given daily subcutaneous injections of <protein>human leukocyte interferon</protein> ( 3 X 10 ( 6 ) units/day ) from the 3rd through 23rd day of the menstrual cycle , and serum steroid and peptide hormone concentrations monitored at 3-day intervals during the treatment and the preceding control cycle ."}968{"id": "967", "text": "Concentrations of cytosol and nuclear estrogen receptors ( ERC and ERN , respectively ) and progestin receptors ( PRC and PRN ) were also measured from endometrial biopsies taken on the 24th day of the control and treatment cycle .", "annotated_text": "Concentrations of <protein>cytosol and nuclear estrogen receptors</protein> ( <protein>ERC</protein> and <protein>ERN</protein> , respectively ) and <protein>progestin receptors</protein> ( <protein>PRC</protein> and <protein>PRN</protein> ) were also measured from endometrial biopsies taken on the 24th day of the control and treatment cycle ."}969{"id": "968", "text": "In addition , an extensive monitoring of clinical chemical and hematological tests from the blood samples were performed .", "annotated_text": "In addition , an extensive monitoring of clinical chemical and hematological tests from the blood samples were performed ."}970{"id": "969", "text": "Serum estradiol and progesterone concentrations were significantly decreased during the treatment cycle , suggesting that interferon interacts in vivo with the function of both FSH and LH .", "annotated_text": "Serum estradiol and progesterone concentrations were significantly decreased during the treatment cycle , suggesting that <protein>interferon</protein> interacts in vivo with the function of both FSH and LH ."}971{"id": "970", "text": "No significant changes were observed in the serum peptide hormone concentrations measured ( FSH , LH , prolactin , insulin , growth hormone and TSH ) ; neither were the levels of endometrial ERC , ERN , PRC and PRN affected by interferon administration .", "annotated_text": "No significant changes were observed in the serum peptide hormone concentrations measured ( FSH , LH , prolactin , insulin , growth hormone and TSH ) ; neither were the levels of <protein>endometrial ERC , ERN , PRC and PRN</protein> affected by <protein>interferon</protein> administration ."}972{"id": "971", "text": "As expected , interferon administration resulted in decreased leukocyte counts .", "annotated_text": "As expected , <protein>interferon</protein> administration resulted in decreased <cell_type>leukocyte</cell_type> counts ."}973{"id": "972", "text": "Moreover , an increasing tendency in the activities of serum alkaline phosphatase and gamma-glutamyltransferase during the interferon therapy shows that interferon may slightly interfere with the liver function .", "annotated_text": "Moreover , an increasing tendency in the activities of <protein>serum alkaline phosphatase</protein> and <protein>gamma-glutamyltransferase</protein> during the <protein>interferon</protein> therapy shows that <protein>interferon</protein> may slightly interfere with the liver function ."}974{"id": "973", "text": "These results suggest that one of the mechanisms by which interferon treatment may affect the growth of hormone-dependent neoplasms could be the interaction with production and/or function of circulating hormonal compounds .", "annotated_text": "These results suggest that one of the mechanisms by which <protein>interferon</protein> treatment may affect the growth of hormone-dependent neoplasms could be the interaction with production and/or function of circulating hormonal compounds ."}975{"id": "974", "text": "[ Glucocorticoid receptor level in the blood leukocytes in different acute diseases ]", "annotated_text": "[ <protein>Glucocorticoid receptor</protein> level in the <cell_type>blood leukocytes</cell_type> in different acute diseases ]"}976{"id": "975", "text": "Content of glucocorticoid receptors in cytosol of blood leukocytes , concentration of cortisol and amount of leukocytes in blood were studied in 20 patients with acute impairments within the second day of the disease .", "annotated_text": "Content of <protein>glucocorticoid receptors</protein> in cytosol of <cell_type>blood leukocytes</cell_type> , concentration of cortisol and amount of <cell_type>leukocytes</cell_type> in blood were studied in 20 patients with acute impairments within the second day of the disease ."}977{"id": "976", "text": "Content of receptors in cytosol of blood leukocytes was studied using 3H-triamcinolone acetonide .", "annotated_text": "Content of receptors in cytosol of blood leukocytes was studied using 3H-triamcinolone acetonide ."}978{"id": "977", "text": "Distinct increase in amount of the leukocyte glucocorticoid receptors was found in patients with poisoning by dichlorethane and hypnotic drugs under conditions of acute myocardial infarction .", "annotated_text": "Distinct increase in amount of the <protein>leukocyte glucocorticoid receptors</protein> was found in patients with poisoning by dichlorethane and hypnotic drugs under conditions of acute myocardial infarction ."}979{"id": "978", "text": "In acute pancreatitis content of the leukocyte receptors was not altered as compared with controls .", "annotated_text": "In acute pancreatitis content of the <protein>leukocyte receptors</protein> was not altered as compared with controls ."}980{"id": "979", "text": "Concentration of endogenous cortisol was increased in blood of all the patients , except of the cases of acetate intoxication .", "annotated_text": "Concentration of endogenous cortisol was increased in blood of all the patients , except of the cases of acetate intoxication ."}981{"id": "980", "text": "Reverse correlation was observed between concentration of cortisol in blood and content of glucocorticoid receptors in leukocytes .", "annotated_text": "Reverse correlation was observed between concentration of cortisol in blood and content of glucocorticoid receptors in <cell_type>leukocytes</cell_type> ."}982{"id": "981", "text": "But in the patients with acute pancreatitis the decrease in content of leukocyte glucocorticoid receptors was not observed although there was an increase in cortisol concentration in blood .", "annotated_text": "But in the patients with acute pancreatitis the decrease in content of <protein>leukocyte glucocorticoid receptors</protein> was not observed although there was an increase in cortisol concentration in blood ."}983{"id": "982", "text": "The role of glucocorticoid receptors in immunological processes under conditions of purulent complications and possibility to regulate the metabolism in leukocytes", "annotated_text": "The role of <protein>glucocorticoid receptors</protein> in immunological processes under conditions of purulent complications and possibility to regulate the metabolism in <cell_type>leukocytes</cell_type>"}984{"id": "983", "text": "Therapeutic concentrations of glucocorticoids suppress the antimicrobial activity of human macrophages without impairing their responsiveness to gamma interferon .", "annotated_text": "Therapeutic concentrations of glucocorticoids suppress the antimicrobial activity of <cell_type>human macrophages</cell_type> without impairing their responsiveness to <protein>gamma interferon</protein> ."}985{"id": "984", "text": "By exposing human blood-derived macrophages and alveolar macrophages in vitro to dexamethasone , we showed in these studies that glucocorticoids markedly suppress the antimicrobial activity of macrophages but not macrophage activation by lymphokines .", "annotated_text": "By exposing <cell_type>human blood-derived macrophages and alveolar macrophages</cell_type> in vitro to dexamethasone , we showed in these studies that glucocorticoids markedly suppress the antimicrobial activity of <cell_type>macrophages</cell_type> but not <cell_type>macrophage</cell_type> activation by <cell_type>lymphokines</cell_type> ."}986{"id": "985", "text": "As little as 2.5 X 10 ( -8 ) mol/liter of dexamethasone prevented macrophages from inhibiting germination of Aspergillus spores or from eliminating ingested bacteria such as Listeria , Nocardia , or Salmonella .", "annotated_text": "As little as 2.5 X 10 ( -8 ) mol/liter of dexamethasone prevented <cell_type>macrophages</cell_type> from inhibiting germination of Aspergillus spores or from eliminating ingested bacteria such as Listeria , Nocardia , or Salmonella ."}987{"id": "986", "text": "Damage to macrophage function was inhibited by progesterone and appeared to be receptor-mediated .", "annotated_text": "Damage to <cell_type>macrophage</cell_type> function was inhibited by progesterone and appeared to be receptor-mediated ."}988{"id": "987", "text": "In accordance with in vivo observations , dexamethasone required 24-36 h to suppress antimicrobial activity .", "annotated_text": "In accordance with in vivo observations , dexamethasone required 24-36 h to suppress antimicrobial activity ."}989{"id": "988", "text": "While glucocorticoids interfered with base-line activity of macrophages , dexamethasone concentrations comparable to drug levels in patients had no effect on macrophage activation .", "annotated_text": "While glucocorticoids interfered with base-line activity of <cell_type>macrophages</cell_type> , dexamethasone concentrations comparable to drug levels in patients had no effect on <cell_type>macrophage</cell_type> activation ."}990{"id": "989", "text": "Proliferating lymphocytes and gamma-interferon thus increased the antimicrobial activity of phagocytes exposed to glucocorticoids over that of control cells .", "annotated_text": "Proliferating <cell_type>lymphocytes</cell_type> and <protein>gamma-interferon</protein> thus increased the antimicrobial activity of <cell_type>phagocytes</cell_type> exposed to glucocorticoids over that of control cells ."}991{"id": "990", "text": "Macrophage activation and correction of the dexamethasone effect by gamma-interferon , however , was dependent on the pathogen .", "annotated_text": "Macrophage activation and correction of the dexamethasone effect by <protein>gamma-interferon</protein> , however , was dependent on the pathogen ."}992{"id": "991", "text": "The lymphokine enhanced the antimicrobial activity of dexamethasone-treated macrophages against Listeria and Salmonella but not against Aspergillus or Nocardia .", "annotated_text": "The <protein>lymphokine</protein> enhanced the antimicrobial activity of <cell_line>dexamethasone-treated macrophages</cell_line> against Listeria and Salmonella but not against Aspergillus or Nocardia ."}993{"id": "992", "text": "Dexamethasone-induced damage to the antimicrobial activity of human macrophages in vitro parallels observations that glucocorticoids render laboratory animals susceptible to listeriosis and aspergillosis by damaging resident macrophages .", "annotated_text": "Dexamethasone-induced damage to the antimicrobial activity of <cell_type>human macrophages</cell_type> in vitro parallels observations that glucocorticoids render laboratory animals susceptible to listeriosis and aspergillosis by damaging resident <cell_line>macrophages</cell_line> ."}994{"id": "993", "text": "Suppression of macrophage antimicrobial activity should thus be considered when treating patients with glucocorticoids ; its prevention by gamma-interferon might be beneficial for some but not all pathogens .", "annotated_text": "Suppression of <cell_type>macrophage</cell_type> antimicrobial activity should thus be considered when treating patients with glucocorticoids ; its prevention by <protein>gamma-interferon</protein> might be beneficial for some but not all pathogens ."}995{"id": "994", "text": "Interleukin 2 receptor ( Tac antigen ) expression in HTLV-I-associated adult T-cell leukemia .", "annotated_text": "<protein>Interleukin 2 receptor</protein> ( <protein>Tac antigen</protein> ) expression in HTLV-I-associated adult <cell_type>T-cell</cell_type> leukemia ."}996{"id": "995", "text": "Interleukin-2 ( IL-2 ) is a lymphokine synthesized by some T-cells following activation .", "annotated_text": "<protein>Interleukin-2</protein> ( <protein>IL-2</protein> ) is a <protein>lymphokine</protein> synthesized by some <cell_type>T-cells</cell_type> following activation ."}997{"id": "996", "text": "Resting T-cells do not express IL-2 receptors , but receptors are rapidly expressed on T-cells following interaction of antigens , mitogens , or monoclonal antibodies with the antigen-specific T-cell receptor complex .", "annotated_text": "Resting <cell_type>T-cells</cell_type> do not express <protein>IL-2 receptors</protein> , but receptors are rapidly expressed on <cell_type>T-cells</cell_type> following interaction of antigens , mitogens , or <protein>monoclonal antibodies</protein> with the <protein>antigen-specific T-cell receptor complex</protein> ."}998{"id": "997", "text": "Using anti-Tac , a monoclonal antibody that recognizes the IL-2 receptor , the receptor has been purified and shown to be a Mr 33 , 000 peptide that is posttranslationally glycosylated to a Mr 55 , 000 mature form .", "annotated_text": "Using <protein>anti-Tac</protein> , a <protein>monoclonal antibody</protein> that recognizes the <protein>IL-2 receptor</protein> , the receptor has been purified and shown to be a Mr 33 , 000 peptide that is posttranslationally glycosylated to a Mr 55 , 000 mature form ."}999{"id": "998", "text": "Normal resting T-cells and most leukemic T-cell populations do not express IL-2 receptors ; however , the leukemic cells of the 11 patients examined who had human T-cell lymphotropic virus-associated adult T-cell leukemia expressed the Tac antigen .", "annotated_text": "Normal resting <cell_type>T-cells</cell_type> and most <cell_line>leukemic T-cell populations</cell_line> do not express <protein>IL-2 receptors</protein> ; however , the <cell_type>leukemic cells</cell_type> of the 11 patients examined who had human T-cell lymphotropic virus-associated adult T-cell leukemia expressed the <protein>Tac antigen</protein> ."}1000{"id": "999", "text": "In human T-cell lymphotropic virus-I infected cells , the Mr 42 , 000 long open reading frame protein encoded in part by the pX region of this virus may act as a transacting transcriptional activator that induces IL-2 receptor gene transcription , thus providing an explanation for the constant association of IL-2 receptor expression with adult T-cell lymphotropic virus-I infection of lymphoid cells .", "annotated_text": "In <cell_type>human T-cell lymphotropic virus-I infected cells</cell_type> , the Mr 42 , 000 long <protein>open reading frame protein</protein> encoded in part by the <dna>pX region</dna> of this virus may act as a <protein>transacting transcriptional activator</protein> that induces <dna>IL-2 receptor gene</dna> transcription , thus providing an explanation for the constant association of <protein>IL-2 receptor</protein> expression with adult T-cell lymphotropic virus-I infection of <cell_type>lymphoid cells</cell_type> ."}1001{"id": "1000", "text": "The constant expression of large numbers of IL-2 receptors which may be aberrant may play a role in the uncontrolled growth of adult T-cell leukemia cells .", "annotated_text": "The constant expression of large numbers of <protein>IL-2 receptors</protein> which may be aberrant may play a role in the uncontrolled growth of <cell_type>adult T-cell leukemia cells</cell_type> ."}1002{"id": "1001", "text": "Two patients with Tac-positive adult T-cell leukemia have been treated with the anti-Tac .", "annotated_text": "Two patients with Tac-positive adult T-cell leukemia have been treated with the <protein>anti-Tac</protein> ."}1003{"id": "1002", "text": "One of the patients had 6- and 3-mo remissions of his leukemia following two courses of therapy with this monoclonal antibody directed toward this growth factor receptor .", "annotated_text": "One of the patients had 6- and 3-mo remissions of his leukemia following two courses of therapy with this <protein>monoclonal antibody</protein> directed toward this <protein>growth factor receptor</protein> ."}1004{"id": "1003", "text": "Lymphocyte glucocorticoid receptor binding in depressed patients with hypercortisolemia .", "annotated_text": "<cell_type>Lymphocyte</cell_type> <protein>glucocorticoid receptor</protein> binding in depressed patients with hypercortisolemia ."}1005{"id": "1004", "text": "Despite elevated levels of serum and urinary cortisol , patients with depressive illness manifest none of the clinical stigmata of glucocorticoid excess .", "annotated_text": "Despite elevated levels of serum and urinary cortisol , patients with depressive illness manifest none of the clinical stigmata of glucocorticoid excess ."}1006{"id": "1005", "text": "This hypercortisolemia in the absence of clinical effects suggests a state of hormone resistance and could be mediated by alterations in the glucocorticoid receptor .", "annotated_text": "This hypercortisolemia in the absence of clinical effects suggests a state of hormone resistance and could be mediated by alterations in the <protein>glucocorticoid receptor</protein> ."}1007{"id": "1006", "text": "Earlier studies have shown that small doses of glucocorticoids cause a decrease in glucocorticoid receptor binding in normal human lymphocytes .", "annotated_text": "Earlier studies have shown that small doses of glucocorticoids cause a decrease in <protein>glucocorticoid receptor</protein> binding in normal <cell_type>human lymphocytes</cell_type> ."}1008{"id": "1007", "text": "White cells from depressed patients with significant hypercortisolemia would be expected to show a similar change in receptor concentration if peripheral tissues are adequately exposed to and sensitive to the hormone .", "annotated_text": "White cells from depressed patients with significant hypercortisolemia would be expected to show a similar change in receptor concentration if peripheral tissues are adequately exposed to and sensitive to the hormone ."}1009{"id": "1008", "text": "In this study we compared the binding of [ 3H ] dexamethasone to lymphocytes from normal subjects and depressed patients with hypercortisolemia .", "annotated_text": "In this study we compared the binding of [ 3H ] dexamethasone to <cell_type>lymphocytes</cell_type> from normal subjects and depressed patients with hypercortisolemia ."}1010{"id": "1009", "text": "Lymphocytes from normal subjects had a mean receptor concentration of 10.2 +/- 0.66 fm/10 ( 6 ) cells ( S.E.M. ) and a dissociation constant of 4.8 +/- 0.47 nM .", "annotated_text": "<cell_type>Lymphocytes</cell_type> from normal subjects had a mean receptor concentration of 10.2 +/- 0.66 fm/10 ( 6 ) cells ( S.E.M. ) and a dissociation constant of 4.8 +/- 0.47 nM ."}1011{"id": "1010", "text": "Lymphocytes from depressed patients with abnormal 0800 h serum cortisol after dexamethasone had a mean receptor concentration of 8.8 +/- 0.75 fm/10 ( 6 ) cells , which was not significantly different from that in lymphocytes from normal subjects or from depressed subjects with normal post-dexamethasone cortisol levels ( 9.4 +/- 0.95 fm/10 ( 6 ) cells ) .", "annotated_text": "<cell_type>Lymphocytes</cell_type> from depressed patients with abnormal 0800 h serum cortisol after dexamethasone had a mean receptor concentration of 8.8 +/- 0.75 fm/10 ( 6 ) cells , which was not significantly different from that in <cell_type>lymphocytes</cell_type> from normal subjects or from depressed subjects with normal post-dexamethasone cortisol levels ( 9.4 +/- 0.95 fm/10 ( 6 ) cells ) ."}1012{"id": "1011", "text": "Lymphocytes from depressed patients with elevated urinary free cortisol excretion ( UFC ) also had normal receptor concentration and binding affinity for dexamethasone .", "annotated_text": "<cell_type>Lymphocytes</cell_type> from depressed patients with elevated urinary free cortisol excretion ( UFC ) also had normal receptor concentration and binding affinity for dexamethasone ."}1013{"id": "1012", "text": "The lack of a change in lymphocyte glucocorticoid receptor concentration in the presence of cortisol excess suggests the possibility that hypercortisolemia in depressive illness represents a state of peripheral glucocorticoid resistance .", "annotated_text": "The lack of a change in <cell_type>lymphocyte</cell_type> <protein>glucocorticoid receptor</protein> concentration in the presence of cortisol excess suggests the possibility that hypercortisolemia in depressive illness represents a state of peripheral glucocorticoid resistance ."}1014{"id": "1013", "text": "Structure and regulation of the glucocorticoid hormone receptor .", "annotated_text": "Structure and regulation of the <protein>glucocorticoid hormone receptor</protein> ."}1015{"id": "1014", "text": "The glucocorticoid receptor is an intracellular protein which possesses three distinct domains , one that binds agonist and antagonist steroids , one that binds DNA , and one that binds anti-receptor antibodies and is required for glucocorticoid modulation of gene expression .", "annotated_text": "The <protein>glucocorticoid receptor</protein> is an <protein>intracellular protein</protein> which possesses three distinct domains , one that binds agonist and antagonist steroids , one that binds DNA , and one that binds <protein>anti-receptor antibodies</protein> and is required for glucocorticoid modulation of gene expression ."}1016{"id": "1015", "text": "In intact cells , receptor number , affinity and activity can change in response to factors that bind to the receptor , or that act indirectly through ill-defined mechanisms which may include resumption or arrest of cell cycling and variations in intracellular calcium ion concentrations .", "annotated_text": "In intact cells , receptor number , affinity and activity can change in response to factors that bind to the receptor , or that act indirectly through ill-defined mechanisms which may include resumption or arrest of cell cycling and variations in intracellular calcium ion concentrations ."}1017{"id": "1016", "text": "Some of these factors appear to exert their effect by controlling critical receptor properties such as ATP-dependent phosphorylation , integrity of thiol groups , and exposure of key amino acid residues .", "annotated_text": "Some of these factors appear to exert their effect by controlling critical receptor properties such as ATP-dependent phosphorylation , integrity of <protein>thiol groups</protein> , and exposure of <protein>key amino acid residues</protein> ."}1018{"id": "1017", "text": "Glucocorticoid agonists promote the 'transformation ' of the receptor into the DNA-binding state , which is competent for modulating gene expression .", "annotated_text": "Glucocorticoid agonists promote the 'transformation ' of the receptor into the DNA-binding state , which is competent for modulating gene expression ."}1019{"id": "1018", "text": "Glucocorticoid antagonists are steroids that interact with the receptor but either fail to produce a stable complex or produce a stable but inefficient complex .", "annotated_text": "Glucocorticoid antagonists are steroids that interact with the receptor but either fail to produce a <protein>stable complex</protein> or produce a <protein>stable but inefficient complex</protein> ."}1020{"id": "1019", "text": "Although substituent groups that confer agonist or antagonist activity to the steroid have been identified , the molecular determinants of this difference at the receptor level remain unknown .", "annotated_text": "Although substituent groups that confer agonist or antagonist activity to the steroid have been identified , the molecular determinants of this difference at the receptor level remain unknown ."}1021{"id": "1020", "text": "Most in vitro and in vivo data on receptor regulation can be accommodated by postulating the existence of an intracellular cycle that involves five states of the receptor .", "annotated_text": "Most in vitro and in vivo data on receptor regulation can be accommodated by postulating the existence of an intracellular cycle that involves five states of the receptor ."}1022{"id": "1021", "text": "The active free receptor is phosphorylated , reduced , and presumably oligomeric ( state A ) .", "annotated_text": "The active free receptor is phosphorylated , reduced , and presumably oligomeric ( state A ) ."}1023{"id": "1022", "text": "Following binding of an agonist ( state B ) , it can become transformed by dissociation into its subunits and dephosphorylation ( state C ) .", "annotated_text": "Following binding of an agonist ( state B ) , it can become transformed by dissociation into its subunits and dephosphorylation ( state C ) ."}1024{"id": "1023", "text": "The transformed receptor then interacts with chromatin ( state D ) .", "annotated_text": "The <protein>transformed receptor</protein> then interacts with <dna>chromatin</dna> ( state D ) ."}1025{"id": "1024", "text": "Dissociation of the steroid and oxidation of receptor thiol group ( s ) lead to the inactive receptor form ( state E ) .", "annotated_text": "Dissociation of the steroid and oxidation of <protein>receptor thiol group</protein> ( s ) lead to the inactive receptor form ( state E ) ."}1026{"id": "1025", "text": "Reduction and rephosphorylation of the receptor enable it to bind steroids again so that the cycle is closed .", "annotated_text": "Reduction and rephosphorylation of the receptor enable it to bind steroids again so that the cycle is closed ."}1027{"id": "1026", "text": "Thermodynamics of steroid binding to the human glucocorticoid receptor .", "annotated_text": "Thermodynamics of steroid binding to the <protein>human glucocorticoid receptor</protein> ."}1028{"id": "1027", "text": "The thermodynamics of the interaction of glucocorticoids with their receptor were studied in cytosol from human lymphoblastoid cells .", "annotated_text": "The thermodynamics of the interaction of glucocorticoids with their receptor were studied in cytosol from <cell_type>human lymphoblastoid cells</cell_type> ."}1029{"id": "1028", "text": "The rate and affinity constants of dexamethasone and cortisol between 0 degree and 25 degrees C were calculated by curve-fitting from time-course and equilibrium kinetics .", "annotated_text": "The rate and affinity constants of dexamethasone and cortisol between 0 degree and 25 degrees C were calculated by curve-fitting from time-course and equilibrium kinetics ."}1030{"id": "1029", "text": "The data were consistent with a simple reversible bimolecular interaction .", "annotated_text": "The data were consistent with a simple reversible bimolecular interaction ."}1031{"id": "1030", "text": "Arrhenius and Va n't Hoff plots were curvilinear for both steroids .", "annotated_text": "Arrhenius and Va n't Hoff plots were curvilinear for both steroids ."}1032{"id": "1031", "text": "At equilibrium , the solution for the equation delta G = delta H - T X delta S ( eqn. 1 ) was ( in kJ X mol-1 ) -47 = 36 - 83 ( dexamethasone ) and -42 = -9 - 33 ( cortisol ) at 0 degree C .", "annotated_text": "At equilibrium , the solution for the equation delta G = delta H - T X delta S ( eqn. 1 ) was ( in kJ X mol-1 ) -47 = 36 - 83 ( dexamethasone ) and -42 = -9 - 33 ( cortisol ) at 0 degree C ."}1033{"id": "1032", "text": "Enthalpy and entropy changes decreased quasi-linearly with temperature such that , at 25 degrees C , the respective values were -50 = -75 + 25 and -43 = -48 + 5 .", "annotated_text": "Enthalpy and entropy changes decreased quasi-linearly with temperature such that , at 25 degrees C , the respective values were -50 = -75 + 25 and -43 = -48 + 5 ."}1034{"id": "1033", "text": "Thus , for both steroids , the interaction was entropy-driven at low temperature and became entirely enthalpy-driven at 20 degrees C .", "annotated_text": "Thus , for both steroids , the interaction was entropy-driven at low temperature and became entirely enthalpy-driven at 20 degrees C ."}1035{"id": "1034", "text": "Thermodynamic values for the transition state were calculated from the rate constants .", "annotated_text": "Thermodynamic values for the transition state were calculated from the rate constants ."}1036{"id": "1035", "text": "For the forward reaction , eqn. ( 1 ) gave 45 = 84 - 39 ( dexamethasone ) and 46 = 60 - 14 ( cortisol ) at 0 degree C , and 44 = 24 + 20 ( dexamethasone ) and 46 = 28 + 18 ( cortisol ) at 25 degrees C .", "annotated_text": "For the forward reaction , eqn. ( 1 ) gave 45 = 84 - 39 ( dexamethasone ) and 46 = 60 - 14 ( cortisol ) at 0 degree C , and 44 = 24 + 20 ( dexamethasone ) and 46 = 28 + 18 ( cortisol ) at 25 degrees C ."}1037{"id": "1036", "text": "These data fit quite well with a two-step model [ Ross & Subramanian ( 1981 ) Biochemistry 20 , 3096-3102 ] proposed for ligand-protein interactions , which involves a partial immobilization of the reacting species governed by hydrophobic forces , followed by stabilization of the complex by short-range interactions .", "annotated_text": "These data fit quite well with a two-step model [ Ross & Subramanian ( 1981 ) Biochemistry 20 , 3096-3102 ] proposed for ligand-protein interactions , which involves a partial immobilization of the reacting species governed by hydrophobic forces , followed by stabilization of the complex by short-range interactions ."}1038{"id": "1037", "text": "On the basis of this model , an analysis of the transition-state thermodynamics led to the conclusion that no more than half of the steroid molecular area is engaged in the binding process .", "annotated_text": "On the basis of this model , an analysis of the transition-state thermodynamics led to the conclusion that no more than half of the steroid molecular area is engaged in the binding process ."}1039{"id": "1038", "text": "Cell cycle-related changes in number of T-lymphocyte receptors for glucocorticoids and insulin .", "annotated_text": "Cell cycle-related changes in number of <protein>T-lymphocyte receptors</protein> for glucocorticoids and insulin ."}1040{"id": "1039", "text": "Enriched human peripheral T-lymphocytes were stimulated with PHA and examined for variations in insulin and glucocorticoid ( dexamethasone ) receptor numbers during the early phases of the cell cycle .", "annotated_text": "Enriched <cell_type>human peripheral T-lymphocytes</cell_type> were stimulated with PHA and examined for variations in insulin and glucocorticoid ( dexamethasone ) receptor numbers during the early phases of the cell cycle ."}1041{"id": "1040", "text": "Cells in G0 , G1a and G1b phases , where the G1a - G1b transition is an Interleukin 2 dependent event , were quantitated by flow cytometry .", "annotated_text": "Cells in G0 , G1a and G1b phases , where the G1a - G1b transition is an <protein>Interleukin 2</protein> dependent event , were quantitated by flow cytometry ."}1042{"id": "1041", "text": "Few but significant numbers of glucocorticoid receptors ( 2700/cell ) and no insulin receptors ( -1/cell ) were found in the resting ( G0 ) phase .", "annotated_text": "Few but significant numbers of <protein>glucocorticoid receptors</protein> ( 2700/cell ) and no <protein>insulin receptors</protein> ( -1/cell ) were found in the resting ( G0 ) phase ."}1043{"id": "1042", "text": "As cells entered the G1a phase the specific binding of dexamethasone increased and of insulin took place .", "annotated_text": "As cells entered the G1a phase the specific binding of dexamethasone increased and of insulin took place ."}1044{"id": "1043", "text": "Although the specific binding further increased as T-cells entered the G1b phase ( as measured at 44 h of incubation and using hydroxyurea-treated cells ) , the major changes in the specific binding of dexamethasone took place during the period 16 - 20 h after stimulation .", "annotated_text": "Although the specific binding further increased as <cell_type>T-cells</cell_type> entered the G1b phase ( as measured at 44 h of incubation and using <cell_line>hydroxyurea-treated cells</cell_line> ) , the major changes in the specific binding of dexamethasone took place during the period 16 - 20 h after stimulation ."}1045{"id": "1044", "text": "Based on these findings , it is concluded that both receptor types ( cell membrane and cytoplasmic receptors ) are being formed and increased at G1 phase prior to cell proliferation , indicating the importance of G1 phase in immunoregulation .", "annotated_text": "Based on these findings , it is concluded that both receptor types ( <protein>cell membrane and cytoplasmic receptors</protein> ) are being formed and increased at G1 phase prior to cell proliferation , indicating the importance of G1 phase in immunoregulation ."}1046{"id": "1045", "text": "Glucocorticoid receptors and cortico-sensitivity in a human clonal monocytic cell line , CM-SM .", "annotated_text": "<protein>Glucocorticoid receptors</protein> and cortico-sensitivity in a <cell_line>human clonal monocytic cell line</cell_line> , <cell_line>CM-SM</cell_line> ."}1047{"id": "1046", "text": "CM-SM is a clonal line of human precursor mononuclear phagocytes inducible to macrophage differentiation in response to the tumor promoter phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate ( TPA ) .", "annotated_text": "<cell_line>CM-SM</cell_line> is a <cell_line>clonal line</cell_line> of <cell_type>human precursor mononuclear phagocytes</cell_type> inducible to <cell_type>macrophage</cell_type> differentiation in response to the tumor promoter phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate ( TPA ) ."}1048{"id": "1047", "text": "Untreated CM-SM cells contain single class , high-affinity ( KD = 4.0 X 10 ( -9 ) M ) glucocorticoid-specific receptor sites ( approximately 60 , 000 per cell ) , as measured by a whole cell assay , at 37 degrees C , using [ 3H ] triamcinolone acetonide ( TA ) .", "annotated_text": "Untreated CM-SM cells contain single class , high-affinity ( KD = 4.0 X 10 ( -9 ) M ) glucocorticoid-specific receptor sites ( approximately 60 , 000 per cell ) , as measured by a whole cell assay , at 37 degrees C , using [ 3H ] triamcinolone acetonide ( TA ) ."}1049{"id": "1048", "text": "Exposure of CM-SM to dexamethasone ( DEX ) produced a progressive , dose- and time-related series of changes in CM-SM cell growth , saturation density , morphology , and functional properties , with half-maximal effects at about 10 ( -9 ) M for DEX .", "annotated_text": "Exposure of <cell_line>CM-SM</cell_line> to dexamethasone ( DEX ) produced a progressive , dose- and time-related series of changes in <cell_line>CM-SM</cell_line> cell growth , saturation density , morphology , and functional properties , with half-maximal effects at about 10 ( -9 ) M for DEX ."}1050{"id": "1049", "text": "TA-receptor sites rapidly decreased ( about 70 % ) after DEX treatment , without any apparent change in steroid specificity and affinity .", "annotated_text": "TA-receptor sites rapidly decreased ( about 70 % ) after DEX treatment , without any apparent change in steroid specificity and affinity ."}1051{"id": "1050", "text": "After 5 days in culture with a saturating concentration ( 3.6 X 10 ( -8 ) M ) of hormone , the cells reached a saturation density of about 9.0 X 10 ( 6 ) viable cells/ml ( about 4.0 X 10 ( 6 ) viable cells/ml in the controls ) , while the modal volume of the resulting cell population was approximately 60 % , as compared to the volume of untreated cells .", "annotated_text": "After 5 days in culture with a saturating concentration ( 3.6 X 10 ( -8 ) M ) of hormone , the cells reached a saturation density of about 9.0 X 10 ( 6 ) viable cells/ml ( about 4.0 X 10 ( 6 ) viable cells/ml in the controls ) , while the modal volume of the resulting <cell_line>cell population</cell_line> was approximately 60 % , as compared to the volume of <cell_line>untreated cells</cell_line> ."}1052{"id": "1051", "text": "DEX-treated cells appeared less differentiated than controls , as assessed by combined morphologic , antigenic , and cytoenzymatic analyses .", "annotated_text": "<cell_line>DEX-treated cells</cell_line> appeared less differentiated than controls , as assessed by combined morphologic , antigenic , and cytoenzymatic analyses ."}1053{"id": "1052", "text": "DEX almost completely inhibited TPA activation of the following macrophage functions : adherency to the culture plate , expression of lysosomal enzymes , Fc and C3 receptors , and stimulation of phagocytosis .", "annotated_text": "DEX almost completely inhibited TPA activation of the following <cell_type>macrophage</cell_type> functions : adherency to the culture plate , expression of <protein>lysosomal enzymes</protein> , <protein>Fc and C3 receptors</protein> , and stimulation of phagocytosis ."}1054{"id": "1053", "text": "After removal of DEX , the cells , within a few passages , returned to a state apparently identical to the untreated controls and could be induced to macrophage differentiation in response to TPA .", "annotated_text": "After removal of DEX , the cells , within a few passages , returned to a state apparently identical to the untreated controls and could be induced to <cell_type>macrophage</cell_type> differentiation in response to TPA ."}1055{"id": "1054", "text": "Acute lymphoblastic leukemia in children : current status , controversies , and future perspective .", "annotated_text": "Acute lymphoblastic leukemia in children : current status , controversies , and future perspective ."}1056{"id": "1055", "text": "Disease-free survival ( DFS ) in childhood ALL is 60 % , and survival in good , average , and poor prognostic groups defined by initial WBC and age is 90 , 60 , and 45 % , respectively .", "annotated_text": "Disease-free survival ( DFS ) in childhood ALL is 60 % , and survival in good , average , and poor prognostic groups defined by initial WBC and age is 90 , 60 , and 45 % , respectively ."}1057{"id": "1056", "text": "Additional immunological , morphological , biochemical , cytokinetic , and cytogenetic factors have been identified , illustrating the heterogeneity of ALL and its derivation from malignant clones at various stages of differentiation and with varying rates of proliferation .", "annotated_text": "Additional immunological , morphological , biochemical , cytokinetic , and cytogenetic factors have been identified , illustrating the heterogeneity of ALL and its derivation from <cell_line>malignant clones</cell_line> at various stages of differentiation and with varying rates of proliferation ."}1058{"id": "1057", "text": "Of biologic importance , these factors may refine further the characteristic features of clinically-determined prognostic groups .", "annotated_text": "Of biologic importance , these factors may refine further the characteristic features of clinically-determined prognostic groups ."}1059{"id": "1058", "text": "Multivariate analysis of large prospective trials with homogeneous therapy will be required to determine the independent prognostic importance of these factors .", "annotated_text": "Multivariate analysis of large prospective trials with homogeneous therapy will be required to determine the independent prognostic importance of these factors ."}1060{"id": "1059", "text": "Current treatment strategies in ALL include ( 1 ) tailoring therapy and its intensity to prognostic groups ; ( 2 ) multiple-drug combinations in induction ; ( 3 ) early use of intrathecal ( IT ) methotrexate ( MTX ) ; ( 4 ) CNS prophylaxis with IT MTX alone in good prognosis patients and combined cranial radiation ( CXRT ) , 1800 rads plus IT MTX , in average and poor prognosis patients .", "annotated_text": "Current treatment strategies in ALL include ( 1 ) tailoring therapy and its intensity to prognostic groups ; ( 2 ) multiple-drug combinations in induction ; ( 3 ) early use of intrathecal ( IT ) methotrexate ( MTX ) ; ( 4 ) CNS prophylaxis with IT MTX alone in good prognosis patients and combined cranial radiation ( CXRT ) , 1800 rads plus IT MTX , in average and poor prognosis patients ."}1061{"id": "1060", "text": "Current studies show a CNS relapse rate of 5 % in all prognostic groups .", "annotated_text": "Current studies show a CNS relapse rate of 5 % in all prognostic groups ."}1062{"id": "1061", "text": "Late neuropsychological defects caused by cranial XRT and IT MTX have prompted programs designed to reduce the potential late toxicity of CNS prophylaxis .", "annotated_text": "Late neuropsychological defects caused by cranial XRT and IT MTX have prompted programs designed to reduce the potential late toxicity of CNS prophylaxis ."}1063{"id": "1062", "text": "More pronounced in younger children , these abnormalities include decreased IQ , visual-motor incoordination , poor performance in mathematics , and memory dysfunction .", "annotated_text": "More pronounced in younger children , these abnormalities include decreased IQ , visual-motor incoordination , poor performance in mathematics , and memory dysfunction ."}1064{"id": "1063", "text": "Until 1980 , more intensive induction , consolidation , and maintenance therapy had failed to prolong DFS in children with a poor prognosis .", "annotated_text": "Until 1980 , more intensive induction , consolidation , and maintenance therapy had failed to prolong DFS in children with a poor prognosis ."}1065{"id": "1064", "text": "In West Germany ( Berlin-Frankfurt-Muenster protocol ) a 70 to 75 % DFS is seen in all patients regardless of initial WBC , suggesting that effective therapy will override prognostic factors .", "annotated_text": "In West Germany ( Berlin-Frankfurt-Muenster protocol ) a 70 to 75 % DFS is seen in all patients regardless of initial WBC , suggesting that effective therapy will override prognostic factors ."}1066{"id": "1065", "text": "Ultra-high-dose MTX , without cranial radiation , is also showing promise in poor prognosis patients .", "annotated_text": "Ultra-high-dose MTX , without cranial radiation , is also showing promise in poor prognosis patients ."}1067{"id": "1066", "text": "Other issues include the optimal duration of therapy , the role of testicular biopsies , and prophylactic testicular radiation .", "annotated_text": "Other issues include the optimal duration of therapy , the role of testicular biopsies , and prophylactic testicular radiation ."}1068{"id": "1067", "text": "Recent studies suggest that prognostic factors lose their significance after 2 years of continuous complete remission and that 2 years of maintenance therapy is adequate .", "annotated_text": "Recent studies suggest that prognostic factors lose their significance after 2 years of continuous complete remission and that 2 years of maintenance therapy is adequate ."}1069{"id": "1068", "text": "Bilateral open-wedge testicular biopsies have identified occult testicular disease in 8 to 10 % of males .", "annotated_text": "Bilateral open-wedge testicular biopsies have identified occult testicular disease in 8 to 10 % of males ."}1070{"id": "1069", "text": "A unified approach to children with leukemia/lymphoma , a group with a particularly poor prognosis , utilizing NHL-type therapy may be more effective than conventional ALL therapy .", "annotated_text": "A unified approach to children with leukemia/lymphoma , a group with a particularly poor prognosis , utilizing NHL-type therapy may be more effective than conventional ALL therapy ."}1071{"id": "1070", "text": "( ABSTRACT TRUNCATED AT 400 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 400 WORDS )"}1072{"id": "1071", "text": "Glucocorticoid receptor and in vitro sensitivity to steroid hormones in human lymphoproliferative diseases and myeloid leukemia .", "annotated_text": "<protein>Glucocorticoid receptor</protein> and in vitro sensitivity to steroid hormones in human lymphoproliferative diseases and myeloid leukemia ."}1073{"id": "1072", "text": "The glucocorticoid receptor ( GR ) quantitation by a whole-cell assay and/or cytosol technique and the in vitro sensitivity to steroids have been assessed in peripheral blood cells from normal donors and patients with chronic lymphatic leukemia ( CLL ) , acute lymphoblastic leukemia ( ALL ) , lymphosarcoma cell leukemia ( LSCL ) , acute nonlymphatic leukemia ( ANLL ) , and chronic myeloid leukemia ( CML ) .", "annotated_text": "The <protein>glucocorticoid receptor</protein> ( <protein>GR</protein> ) quantitation by a whole-cell assay and/or cytosol technique and the in vitro sensitivity to steroids have been assessed in <cell_type>peripheral blood cells</cell_type> from normal donors and patients with chronic lymphatic leukemia ( CLL ) , acute lymphoblastic leukemia ( ALL ) , lymphosarcoma cell leukemia ( LSCL ) , acute nonlymphatic leukemia ( ANLL ) , and chronic myeloid leukemia ( CML ) ."}1074{"id": "1073", "text": "Within the lymphoproliferative diseases , ALL cells exhibited the highest GR concentration ( regardless of the method used ) and the highest in vitro inhibition of spontaneous [ 3H ] thymidine ( [ 3H ] TdR ) uptake by glucocorticoids .", "annotated_text": "Within the lymphoproliferative diseases , <cell_line>ALL cells</cell_line> exhibited the highest <protein>GR</protein> concentration ( regardless of the method used ) and the highest in vitro inhibition of spontaneous [ 3H ] thymidine ( [ 3H ] TdR ) uptake by glucocorticoids ."}1075{"id": "1074", "text": "A significant relationship between GR concentration ( whole-cell assay ) and in vitro sensitivity to dexamethasone was also found .", "annotated_text": "A significant relationship between <protein>GR</protein> concentration ( whole-cell assay ) and in vitro sensitivity to dexamethasone was also found ."}1076{"id": "1075", "text": "On the contrary , CLL cells presented the highest sensitivity to glucocorticoids in PHA-stimulated cell cultures .", "annotated_text": "On the contrary , <cell_line>CLL cells</cell_line> presented the highest sensitivity to glucocorticoids in <cell_line>PHA-stimulated cell cultures</cell_line> ."}1077{"id": "1076", "text": "Cells from the only two ALL patients who did not undergo a remission after glucocorticoid-inclusive chemotherapy had both the lowest in vitro sensitivity to dexamethasone and the lowest GR concentration with whole-cell assay .", "annotated_text": "Cells from the only two ALL patients who did not undergo a remission after glucocorticoid-inclusive chemotherapy had both the lowest in vitro sensitivity to dexamethasone and the lowest GR concentration with whole-cell assay ."}1078{"id": "1077", "text": "Concerning myeloid leukemia , ANLL patients had GR concentrations slightly higher than those found in the ALL group but exhibited the lowest degree of inhibition of spontaneous [ 3H ] TdR uptake by dexamethasone ( stimulatory effects occurred in some cases ) .", "annotated_text": "Concerning myeloid leukemia , ANLL patients had <protein>GR</protein> concentrations slightly higher than those found in the ALL group but exhibited the lowest degree of inhibition of spontaneous [ 3H ] TdR uptake by dexamethasone ( stimulatory effects occurred in some cases ) ."}1079{"id": "1078", "text": "CML cells exhibited an inhibition degree by in vitro glucocorticoids significantly higher than that of ANLL cells but not different from that of lymphoproliferative diseases .", "annotated_text": "<cell_line>CML cells</cell_line> exhibited an inhibition degree by in vitro glucocorticoids significantly higher than that of <cell_line>ANLL cells</cell_line> but not different from that of lymphoproliferative diseases ."}1080{"id": "1079", "text": "No clear relationship among GR pattern , in vitro cell sensitivity to glucocorticoids , and clinicohematologic parameters was observed in myeloid leukemia-bearing patients .", "annotated_text": "No clear relationship among GR pattern , in vitro cell sensitivity to glucocorticoids , and clinicohematologic parameters was observed in myeloid leukemia-bearing patients ."}1081{"id": "1080", "text": "Glucocorticoid receptors and in vitro corticosensitivity of peanut-positive and peanut-negative human thymocyte subpopulations .", "annotated_text": "<protein>Glucocorticoid receptors</protein> and in vitro corticosensitivity of <cell_line>peanut-positive and peanut-negative human thymocyte subpopulations</cell_line> ."}1082{"id": "1081", "text": "In 6 human thymus glands , the immature subset of thymocytes was separated from the more mature one , by differential peanut lectin agglutination .", "annotated_text": "In 6 human thymus glands , the immature subset of <cell_type>thymocytes</cell_type> was separated from the more mature one , by differential peanut lectin agglutination ."}1083{"id": "1082", "text": "These 2 cell subpopulations were analyzed for glucocorticoid receptor content by using a whole cell assay , with ( 3H ) -triamcinolone acetonide as tracer .", "annotated_text": "These 2 cell subpopulations were analyzed for <protein>glucocorticoid receptor</protein> content by using a whole cell assay , with ( 3H ) -triamcinolone acetonide as tracer ."}1084{"id": "1083", "text": "The unagglutinated thymocytes ( peanut negative ) contained about 2 times more receptor sites per cell than agglutinated ( peanut positive ) ones ( 7650 +/- 1550 S.D. verus 3195 +/- 896 S.D. ) .", "annotated_text": "The <cell_type>unagglutinated thymocytes</cell_type> ( peanut negative ) contained about 2 times more receptor sites per cell than agglutinated ( peanut positive ) ones ( 7650 +/- 1550 S.D. verus 3195 +/- 896 S.D. ) ."}1085{"id": "1084", "text": "The affinity for steroid was similar in both cell subsets , as was the stereospecificity for glucocorticoids , the time-course of steroid-receptor association , and cytoplasmic to nuclear translocation .", "annotated_text": "The affinity for steroid was similar in both cell subsets , as was the stereospecificity for glucocorticoids , the time-course of steroid-receptor association , and cytoplasmic to nuclear translocation ."}1086{"id": "1085", "text": "Despite the greater number of glucocorticoid receptor sites , the peanut-negative thymocyte subpopulation did not differ from the peanut-positive one in its sensitivity to the inhibitory effects of triamcinolone acetonide , as determined by measurements of the incorporation of radiolabeled precursors of protein and DNA .", "annotated_text": "Despite the greater number of <protein>glucocorticoid receptor</protein> sites , the <cell_line>peanut-negative thymocyte subpopulation</cell_line> did not differ from the <cell_line>peanut-positive</cell_line> one in its sensitivity to the inhibitory effects of triamcinolone acetonide , as determined by measurements of the incorporation of radiolabeled precursors of protein and DNA ."}1087{"id": "1086", "text": "Moreover , the peanut-negative subset appeared more resistant in vitro to the steroid-induced cell lysis as compared to the peanut-positive one .", "annotated_text": "Moreover , the <cell_line>peanut-negative subset</cell_line> appeared more resistant in vitro to the steroid-induced cell lysis as compared to the <cell_line>peanut-positive</cell_line> one ."}1088{"id": "1087", "text": "Thus , our data suggest that glucocorticoid receptor density and corticosensitivity are not directly correlated and that the number of glucocorticoid receptor sites may be dependent on the degree of immunologic maturation", "annotated_text": "Thus , our data suggest that glucocorticoid receptor density and corticosensitivity are not directly correlated and that the number of <protein>glucocorticoid receptor</protein> sites may be dependent on the degree of immunologic maturation"}1089{"id": "1088", "text": "Defective binding and function of 1 , 25-dihydroxyvitamin D3 receptors in peripheral mononuclear cells of patients with end-organ resistance to 1 , 25-dihydroxyvitamin D .", "annotated_text": "Defective binding and function of <protein>1 , 25-dihydroxyvitamin D3 receptors</protein> in <cell_type>peripheral mononuclear cells</cell_type> of patients with end-organ resistance to 1 , 25-dihydroxyvitamin D ."}1090{"id": "1089", "text": "Lectin-induced DNA synthesis by peripheral mononuclear cells from 17 normal donors was inhibited ( 40-60 % ) by 1 , 25-dihydroxyvitamin D3 ( 1 , 25 [ OH ] 2D3 ) at physiological concentrations ( 10 ( -10 ) -10 ( -9 ) M ) .", "annotated_text": "Lectin-induced DNA synthesis by <cell_type>peripheral mononuclear cells</cell_type> from 17 normal donors was inhibited ( 40-60 % ) by 1 , 25-dihydroxyvitamin D3 ( 1 , 25 [ OH ] 2D3 ) at physiological concentrations ( 10 ( -10 ) -10 ( -9 ) M ) ."}1091{"id": "1090", "text": "The lymphocytes acquire specific receptors for 1 , 25 ( OH ) 2D3 upon activation by the lectins .", "annotated_text": "The <cell_type>lymphocytes</cell_type> acquire specific receptors for 1 , 25 ( OH ) 2D3 upon activation by the <protein>lectins</protein> ."}1092{"id": "1091", "text": "This process precedes the inhibitory effect of 1 , 25 ( OH ) 2D3 .", "annotated_text": "This process precedes the inhibitory effect of 1 , 25 ( OH ) 2D3 ."}1093{"id": "1092", "text": "We studied lymphocytes from six patients from four different kindreds with the syndrome of hereditary end-organ resistance to 1 , 25 ( OH ) 2D ( the so-called vitamin D-dependent rickets type II ) .", "annotated_text": "We studied <cell_type>lymphocytes</cell_type> from six patients from four different kindreds with the syndrome of hereditary end-organ resistance to 1 , 25 ( OH ) 2D ( the so-called vitamin D-dependent rickets type II ) ."}1094{"id": "1093", "text": "In five patients ( three kindreds ) peripheral blood mononuclear cells did not acquire receptors for 1 , 25 ( OH ) 2D3 upon phytohemagglutinin-induced activation .", "annotated_text": "In five patients ( three kindreds ) <cell_type>peripheral blood mononuclear cells</cell_type> did not acquire receptors for 1 , 25 ( OH ) 2D3 upon phytohemagglutinin-induced activation ."}1095{"id": "1094", "text": "Moreover , in contrast to normal lymphocytes , the mitogenic stimulation of these patients ' lymphocytes by phytohemagglutinin and concanavalin A was not inhibited by 1 , 25 ( OH ) 2D3 .", "annotated_text": "Moreover , in contrast to <cell_type>normal lymphocytes</cell_type> , the mitogenic stimulation of these patients ' <cell_type>lymphocytes</cell_type> by <protein>phytohemagglutinin</protein> and concanavalin A was not inhibited by 1 , 25 ( OH ) 2D3 ."}1096{"id": "1095", "text": "Activated lymphocytes of the sixth patient from a fourth kindred exhibited normal binding of [ 3H ] 1 , 25 ( OH ) 2D3 but the hormone failed to inhibit the mitogenic stimulation .", "annotated_text": "Activated <cell_type>lymphocytes</cell_type> of the sixth patient from a fourth kindred exhibited normal binding of [ 3H ] 1 , 25 ( OH ) 2D3 but the hormone failed to inhibit the mitogenic stimulation ."}1097{"id": "1096", "text": "A similar pattern of the vitamin D effector system was previously observed in fibroblasts cultured from skin biopsies of the same group of patients .", "annotated_text": "A similar pattern of the vitamin D effector system was previously observed in fibroblasts cultured from skin biopsies of the same group of patients ."}1098{"id": "1097", "text": "The conclusions from these findings are : ( a ) the inhibition of mitogenic stimulation by 1 , 25 ( OH ) 2D3 is mediated by specific functional receptors to the hormone ; and ( b ) the receptors for 1 , 25 ( OH ) 2D3 in mononuclear cells are probably controlled genetically by the same mechanisms as the effector system in well-characterized target organs of the hormone , such as intestine and kidney .", "annotated_text": "The conclusions from these findings are : ( a ) the inhibition of mitogenic stimulation by 1 , 25 ( OH ) 2D3 is mediated by <protein>specific functional receptors</protein> to the hormone ; and ( b ) the receptors for 1 , 25 ( OH ) 2D3 in <cell_type>mononuclear cells</cell_type> are probably controlled genetically by the same mechanisms as the effector system in well-characterized target organs of the hormone , such as intestine and kidney ."}1099{"id": "1098", "text": "Glucocorticoid receptors of mononuclear leukocytes from myasthenia gravis patients .", "annotated_text": "<protein>Glucocorticoid receptors</protein> of <cell_type>mononuclear leukocytes</cell_type> from myasthenia gravis patients ."}1100{"id": "1099", "text": "The present study was performed to analyse glucocorticoid receptor ( GR ) binding in peripheral blood mononuclear leukocytes ( MNL ) from 39 myasthenia gravis ( MG ) patients ( unoperated patients ( n = 13 ) , thymectomized patients ( n = 14 ) and patients receiving glucocorticoids : thymectomized ( n = 11 ) and unoperated ( n = 6 ] .", "annotated_text": "The present study was performed to analyse <protein>glucocorticoid receptor</protein> ( <protein>GR</protein> ) binding in <cell_type>peripheral blood mononuclear leukocytes</cell_type> ( <cell_type>MNL</cell_type> ) from 39 myasthenia gravis ( MG ) patients ( unoperated patients ( n = 13 ) , thymectomized patients ( n = 14 ) and patients receiving glucocorticoids : thymectomized ( n = 11 ) and unoperated ( n = 6 ] ."}1101{"id": "1100", "text": "A whole cell binding assay with 3 ( H ) dexamethasone was used .", "annotated_text": "A whole cell binding assay with 3 ( H ) dexamethasone was used ."}1102{"id": "1101", "text": "GR mean values were significantly higher in the MNL of MG patients ( thymectomized or not ) not receiving glucocorticoid than in the MNL of healthy donors .", "annotated_text": "<protein>GR</protein> mean values were significantly higher in the <cell_type>MNL</cell_type> of MG patients ( thymectomized or not ) not receiving glucocorticoid than in the <cell_type>MNL</cell_type> of healthy donors ."}1103{"id": "1102", "text": "Affinity was within the normal range .", "annotated_text": "Affinity was within the normal range ."}1104{"id": "1103", "text": "Sex , age or clinical forms of illness did not influence the results .", "annotated_text": "Sex , age or clinical forms of illness did not influence the results ."}1105{"id": "1104", "text": "In patients receiving prednisone ( Pd ) the GR values were significantly lower than in MG patients without Pd therapy , independent of Pd dose or time of administration .", "annotated_text": "In patients receiving prednisone ( Pd ) the <protein>GR</protein> values were significantly lower than in MG patients without Pd therapy , independent of Pd dose or time of administration ."}1106{"id": "1105", "text": "No differences in receptor binding between normal subjects and MG patients receiving Pd have been found .", "annotated_text": "No differences in receptor binding between normal subjects and MG patients receiving Pd have been found ."}1107{"id": "1106", "text": "Immunological interference of high dose corticosteroids .", "annotated_text": "Immunological interference of high dose corticosteroids ."}1108{"id": "1107", "text": "High-dose corticosteroids ( HDC ) will influence cellular as well as humoral participants of the immune response .", "annotated_text": "High-dose corticosteroids ( HDC ) will influence cellular as well as humoral participants of the immune response ."}1109{"id": "1108", "text": "The lymphoid tissue will decrease in size and weight after prolonged treatment with HDC .", "annotated_text": "The lymphoid tissue will decrease in size and weight after prolonged treatment with HDC ."}1110{"id": "1109", "text": "Lymphocyte functions will be impaired .", "annotated_text": "Lymphocyte functions will be impaired ."}1111{"id": "1110", "text": "Reduced synthesis of B- as well as T-lymphocytes will be seen .", "annotated_text": "Reduced synthesis of <cell_type>B- as well as T-lymphocytes</cell_type> will be seen ."}1112{"id": "1111", "text": "The inhibitory effect on B-cell function can be observed both as decreased serum levels of immunoglobulins and as impaired binding of antibodies and complement to the cellular surface .", "annotated_text": "The inhibitory effect on <cell_type>B-cell</cell_type> function can be observed both as decreased serum levels of <protein>immunoglobulins</protein> and as impaired binding of <protein>antibodies</protein> and complement to the cellular surface ."}1113{"id": "1112", "text": "Reduced T-cell function indicated by impaired stimulation by PHA and porkweed as well as by impaired lymphokinin effects on leukocyte migration inhibition has been reported .", "annotated_text": "Reduced <cell_type>T-cell</cell_type> function indicated by impaired stimulation by <protein>PHA</protein> and <protein>porkweed</protein> as well as by impaired lymphokinin effects on <cell_type>leukocyte</cell_type> migration inhibition has been reported ."}1114{"id": "1113", "text": "Reduced lymphocyte adherence to antigen and suppressed lymphocyte reaction have also been observed .", "annotated_text": "Reduced lymphocyte adherence to antigen and suppressed lymphocyte reaction have also been observed ."}1115{"id": "1114", "text": "Humoral factors involved in chemotaxis , opsonisation , phagocytosis , vascular permeability leading to leakage of fluid and cells and factors involved in lysis of antigens are impaired .", "annotated_text": "Humoral factors involved in chemotaxis , opsonisation , phagocytosis , vascular permeability leading to leakage of fluid and cells and factors involved in lysis of antigens are impaired ."}1116{"id": "1115", "text": "This can be explained partly by the observed reduced complement activation via the alternative as well as the classical pathway in association with HDC therapy .", "annotated_text": "This can be explained partly by the observed reduced complement activation via the alternative as well as the classical pathway in association with HDC therapy ."}1117{"id": "1116", "text": "Acute processes with increased vascular permeability and accumulation of leukocytes as impairing factors could be influenced beneficially by HDC therapy .", "annotated_text": "Acute processes with increased vascular permeability and accumulation of <cell_type>leukocytes</cell_type> as impairing factors could be influenced beneficially by HDC therapy ."}1118{"id": "1117", "text": "This positive effect can be seen in treatment of septic shock or rejection of a transplant .", "annotated_text": "This positive effect can be seen in treatment of septic shock or rejection of a transplant ."}1119{"id": "1118", "text": "However , if sepsis or rejection is not rapidly reversed , complications such as multisystem organ failure and bacteremia are prone to appear .", "annotated_text": "However , if sepsis or rejection is not rapidly reversed , complications such as multisystem organ failure and bacteremia are prone to appear ."}1120{"id": "1119", "text": "Identification of human leukemic glucocorticoid receptors using affinity labeling and anti-human glucocorticoid receptor antibodies .", "annotated_text": "Identification of <protein>human leukemic glucocorticoid receptors</protein> using affinity labeling and <protein>anti-human glucocorticoid receptor antibodies</protein> ."}1121{"id": "1120", "text": "Antisera raised against human lymphoid glucocorticoid receptors were used in combination with the glucocorticoid receptor affinity label [ 3H ] dexamethasone 21-mesylate [ ( 3H ] DM ) to identify the glucocorticoid receptors of the human B-lymphoblastoid cell line IM-9 and the human T-cell leukemic cell line CEM-C7 .", "annotated_text": "Antisera raised against <protein>human lymphoid glucocorticoid receptors</protein> were used in combination with the glucocorticoid receptor affinity label [ 3H ] dexamethasone 21-mesylate [ ( 3H ] DM ) to identify the <protein>glucocorticoid receptors</protein> of the <cell_line>human B-lymphoblastoid cell line</cell_line> <cell_line>IM-9</cell_line> and the <cell_line>human T-cell leukemic cell line</cell_line> <cell_line>CEM-C7</cell_line> ."}1122{"id": "1121", "text": "Antisera were obtained following immunization of New Zealand White rabbits with [ 3H ] triamcinolone acetonide [ ( 3H ] TA ) -glucocorticoid receptor complexes partially purified by two-stage DNA-cellulose chromatography .", "annotated_text": "Antisera were obtained following immunization of New Zealand White rabbits with <protein>[ 3H ] triamcinolone acetonide [ ( 3H ] TA ) -glucocorticoid receptor complexes</protein> partially purified by two-stage DNA-cellulose chromatography ."}1123{"id": "1122", "text": "The presence of anti-human glucocorticoid receptor antibodies was verified by : ( a ) adsorption of [ 3H ] TA-receptor-antibody complexes to Protein A ; ( b ) a shift to higher apparent molecular weight in the elution position from Sephacryl S300 of [ 3H ] TA-receptor complexes incubated with immune serum ; and ( c ) the ability of immune serum to displace [ 3H ] TA-receptor complexes on sucrose gradients .", "annotated_text": "The presence of <protein>anti-human glucocorticoid receptor antibodies</protein> was verified by : ( a ) adsorption of <protein>[ 3H ] TA-receptor-antibody complexes</protein> to <protein>Protein A</protein> ; ( b ) a shift to higher apparent molecular weight in the elution position from Sephacryl S300 of <protein>[ 3H ] TA-receptor complexes</protein> incubated with immune serum ; and ( c ) the ability of immune serum to displace <protein>[ 3H ] TA-receptor complexes</protein> on sucrose gradients ."}1124{"id": "1123", "text": "These antibodies also recognized rat liver and murine S49 cell glucocorticoid receptors .", "annotated_text": "These <protein>antibodies</protein> also recognized rat liver and <protein>murine S49 cell glucocorticoid receptors</protein> ."}1125{"id": "1124", "text": "Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [ 3H ] DM-labeled IM-9 cytosol identified a major competable band with a molecular weight of approximately 90 , 000 , three minor competable components with molecular weights of approximately 78 , 000 , approximately 51 , 000 , and approximately 38 , 500 , and at least 21 other noncompetable components .", "annotated_text": "Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [ 3H ] DM-labeled IM-9 cytosol identified a major competable band with a molecular weight of approximately 90 , 000 , three minor competable components with molecular weights of approximately 78 , 000 , approximately 51 , 000 , and approximately 38 , 500 , and at least 21 other noncompetable components ."}1126{"id": "1125", "text": "Following immunoprecipitation of [ 3H ] DM-labeled cytosol with immune serum , only the Mr 90 , 000 and 78 , 000 components were seen .", "annotated_text": "Following immunoprecipitation of [ 3H ] DM-labeled cytosol with immune serum , only the Mr 90 , 000 and 78 , 000 components were seen ."}1127{"id": "1126", "text": "Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [ 3H ] DM-labeled CEM-C7 cytosol revealed a larger number of [ 3H ] DM-labeled components .", "annotated_text": "Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [ 3H ] DM-labeled CEM-C7 cytosol revealed a larger number of [ 3H ] DM-labeled components ."}1128{"id": "1127", "text": "However , after immunoprecipitation of [ 3H ] DM-labeled CEM-C7 cytosol , a predominant competable component with a molecular weight of 90 , 000 was easily identified .", "annotated_text": "However , after immunoprecipitation of [ 3H ] DM-labeled CEM-C7 cytosol , a predominant competable component with a molecular weight of 90 , 000 was easily identified ."}1129{"id": "1128", "text": "This component was markedly diminished when cytosols from the glucocorticoid receptor-deficient cell line ICR-27 were used .", "annotated_text": "This component was markedly diminished when cytosols from the <cell_line>glucocorticoid receptor-deficient cell line</cell_line> <cell_line>ICR-27</cell_line> were used ."}1130{"id": "1129", "text": "Thus , the combination of affinity labeling and anti-human glucocorticoid receptor antibodies is capable of providing direct physical identification of human lymphoid glucocorticoid receptors .", "annotated_text": "Thus , the combination of affinity labeling and <protein>anti-human glucocorticoid receptor antibodies</protein> is capable of providing direct physical identification of <protein>human lymphoid glucocorticoid receptors</protein> ."}1131{"id": "1130", "text": "Effect of thymosin on glucocorticoid receptor activity and glucocorticoid sensitivity of human thymocytes .", "annotated_text": "Effect of thymosin on <protein>glucocorticoid receptor</protein> activity and glucocorticoid sensitivity of <cell_type>human thymocytes</cell_type> ."}1132{"id": "1131", "text": "Incubation with thymosin fraction 5 , ( TMS F5 at 300 micrograms/ml ) a partially purified thymic factor , reduced the steroid binding activity of human infant thymocytes from 9.6 +/- 2.1 fmole/ml to 5.0 +/- 2.0 fmole/ml .", "annotated_text": "Incubation with thymosin fraction 5 , ( TMS F5 at 300 micrograms/ml ) a partially purified thymic factor , reduced the steroid binding activity of <cell_type>human infant thymocytes</cell_type> from 9.6 +/- 2.1 fmole/ml to 5.0 +/- 2.0 fmole/ml ."}1133{"id": "1132", "text": "The glucocorticoid receptor activity in normal infant thymocytes was found to be 2 , 146 +/- 726 ( s.d. ) sites per cell with dissociation constant of 1.4 +/- 0.6 X 10 ( -8 ) M .", "annotated_text": "The <protein>glucocorticoid receptor</protein> activity in normal infant thymocytes was found to be 2 , 146 +/- 726 ( s.d. ) sites per cell with dissociation constant of 1.4 +/- 0.6 X 10 ( -8 ) M ."}1134{"id": "1133", "text": "TMS F5 also increased the resistance of human thymocytes to the cytolytic effect of dexamethasone ( 2.5 X 10 ( -8 ) M ) to 168.6 +/- 30.2 % of control ( P less than 0.01 ) .", "annotated_text": "TMS F5 also increased the resistance of human thymocytes to the cytolytic effect of dexamethasone ( 2.5 X 10 ( -8 ) M ) to 168.6 +/- 30.2 % of control ( P less than 0.01 ) ."}1135{"id": "1134", "text": "In animals , medullary and peripheral blood T cells are more resistant to glucocorticoids than immature thymic T cells .", "annotated_text": "In animals , <cell_type>medullary and peripheral blood T cells</cell_type> are more resistant to glucocorticoids than <cell_type>immature thymic T cells</cell_type> ."}1136{"id": "1135", "text": "The results show that thymosin can induce changes consistent with differentiation in human thymocytes .", "annotated_text": "The results show that thymosin can induce changes consistent with differentiation in <cell_type>human thymocytes</cell_type> ."}1137{"id": "1136", "text": "These in vitro results are consistent with a physiological role of thymosin in intrathymic T cell maturation in man .", "annotated_text": "These in vitro results are consistent with a physiological role of thymosin in intrathymic T cell maturation in man ."}1138{"id": "1137", "text": "Incubation of a human malignant thymus derived T cell line ( MOLT 3 ) with TMS F5 also resulted in a significant reduction of the number of steroid binding sites to 44.2 +/- 15.3 % of control ( P less than 0.05 ) , but TMS F5 did not significantly reduce the glucocorticoid sensitivity of MOLT 3 cells .", "annotated_text": "Incubation of a <cell_line>human malignant thymus derived T cell line</cell_line> ( <cell_line>MOLT 3</cell_line> ) with TMS F5 also resulted in a significant reduction of the number of steroid binding sites to 44.2 +/- 15.3 % of control ( P less than 0.05 ) , but TMS F5 did not significantly reduce the glucocorticoid sensitivity of <cell_line>MOLT 3 cells</cell_line> ."}1139{"id": "1138", "text": "Specific high-affinity receptors for 1 , 25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells : presence in monocytes and induction in T lymphocytes following activation .", "annotated_text": "<protein>Specific high-affinity receptors</protein> for 1 , 25-dihydroxyvitamin D3 in <cell_type>human peripheral blood mononuclear cells</cell_type> : presence in <cell_type>monocytes</cell_type> and induction in <cell_type>T lymphocytes</cell_type> following activation ."}1140{"id": "1139", "text": "Human peripheral blood monocytes have high affinity binding sites for 1 , 25- ( OH ) 2D3 ( Kd 0.14 nM , sedimentation coefficient 3.7S ) .", "annotated_text": "<cell_type>Human peripheral blood monocytes</cell_type> have high affinity binding sites for 1 , 25- ( OH ) 2D3 ( Kd 0.14 nM , sedimentation coefficient 3.7S ) ."}1141{"id": "1140", "text": "Resting human peripheral blood T lymphocytes , however , do not have a demonstrable 1 , 25- ( OH ) 2D3 receptor .", "annotated_text": "<cell_type>Resting human peripheral blood T lymphocytes</cell_type> , however , do not have a demonstrable <protein>1 , 25- ( OH ) 2D3 receptor</protein> ."}1142{"id": "1141", "text": "After activation with phytohemagglutinin the T cells exhibit the receptor within 24 h , and this expression is blocked by cycloheximide .", "annotated_text": "After activation with <protein>phytohemagglutinin</protein> the <cell_type>T cells</cell_type> exhibit the receptor within 24 h , and this expression is blocked by cycloheximide ."}1143{"id": "1142", "text": "The receptor in activated T lymphocytes has a sedimentation coefficient of 3.7S and a high affinity ( Kd 0.10 nM ) for the ligand .", "annotated_text": "The receptor in <cell_type>activated T lymphocytes</cell_type> has a sedimentation coefficient of 3.7S and a high affinity ( Kd 0.10 nM ) for the ligand ."}1144{"id": "1143", "text": "Effects of chronic glucocorticoid excess in man on insulin binding to circulating cells : differences between endogenous and exogenous hypercorticism .", "annotated_text": "Effects of chronic glucocorticoid excess in man on insulin binding to <cell_type>circulating cells</cell_type> : differences between endogenous and exogenous hypercorticism ."}1145{"id": "1144", "text": "We measured [ 125I ] insulin binding to circulating monocytes or erythrocytes from 16 patients with chronic glucocorticoid excess , 9 chronically treated with prednisone and 7 with adrenocortical hyperfunction .", "annotated_text": "We measured [ 125I ] insulin binding to <cell_type>circulating monocytes or erythrocytes</cell_type> from 16 patients with chronic glucocorticoid excess , 9 chronically treated with prednisone and 7 with adrenocortical hyperfunction ."}1146{"id": "1145", "text": "With monocytes , [ 125I ] insulin binding was iincreased in all patients .", "annotated_text": "With <cell_type>monocytes</cell_type> , [ 125I ] insulin binding was iincreased in all patients ."}1147{"id": "1146", "text": "Analysis of binding data indicated that increased binding in patients treated with prednisone was due to an ncrease in receptor concentration , whereas in patients with adrenocortical hyperfunction , it was due to an increase in receptor affinity .", "annotated_text": "Analysis of binding data indicated that increased binding in patients treated with prednisone was due to an ncrease in receptor concentration , whereas in patients with adrenocortical hyperfunction , it was due to an increase in receptor affinity ."}1148{"id": "1147", "text": "With erythrocytes from patients with adrenocortical hyperfunction there was an increase in receptor affinity and a decrease in receptor concentration , so that the binding of [ 125I ] insulin was normal .", "annotated_text": "With erythrocytes from patients with adrenocortical hyperfunction there was an increase in receptor affinity and a decrease in receptor concentration , so that the binding of [ 125I ] insulin was normal ."}1149{"id": "1148", "text": "The disparity of results between endogenous and exogenous hypercorticism , between the two cell types , and between the present studies and previous studies suggest that the effects of glucocorticoid excess on the insulin receptor are extremely complex and wide-ranging and that in this condition , extrapolations in humans from data with circulating cells to liver and muscle may not be appropriate .", "annotated_text": "The disparity of results between endogenous and exogenous hypercorticism , between the two cell types , and between the present studies and previous studies suggest that the effects of glucocorticoid excess on the <protein>insulin receptor</protein> are extremely complex and wide-ranging and that in this condition , extrapolations in humans from data with <cell_type>circulating cells</cell_type> to liver and muscle may not be appropriate ."}1150{"id": "1149", "text": "Reduced level of cellular glucocorticoid receptors in patients with anorexia nervosa .", "annotated_text": "Reduced level of <protein>cellular glucocorticoid receptors</protein> in patients with anorexia nervosa ."}1151{"id": "1150", "text": "Specific glucocorticoid receptors were measured in circulating mononuclear leukocytes from 12 patients with anorexia nervosa and 21 healthy control subjects .", "annotated_text": "Specific <protein>glucocorticoid receptors</protein> were measured in circulating <cell_type>mononuclear leukocytes</cell_type> from 12 patients with anorexia nervosa and 21 healthy control subjects ."}1152{"id": "1151", "text": "Cells from patients were found to contain a significantly ( p less than 0.01 ) lower level of glucocorticoid receptor ( 3830 +/- 210 sites/cell , mean +/- SE ) than those from controls ( 4930 +/- 250 sites/cell ) .", "annotated_text": "Cells from patients were found to contain a significantly ( p less than 0.01 ) lower level of <protein>glucocorticoid receptor</protein> ( 3830 +/- 210 sites/cell , mean +/- SE ) than those from controls ( 4930 +/- 250 sites/cell ) ."}1153{"id": "1152", "text": "A partial glucocorticoid receptor defect may well explain the abnormal cortisol metabolism and glucocorticoid resistance commonly found in patients with anorexia nervosa .", "annotated_text": "A partial <protein>glucocorticoid receptor</protein> defect may well explain the abnormal cortisol metabolism and glucocorticoid resistance commonly found in patients with anorexia nervosa ."}1154{"id": "1153", "text": "Regulation of the glucocorticoid receptor in human lymphocytes .", "annotated_text": "Regulation of the <protein>glucocorticoid receptor</protein> in <cell_type>human lymphocytes</cell_type> ."}1155{"id": "1154", "text": "The presence of a glucocorticoid receptor in human lymphocytes is well established , but factors affecting its regulation have not been described .", "annotated_text": "The presence of a <protein>glucocorticoid receptor</protein> in <cell_type>human lymphocytes</cell_type> is well established , but factors affecting its regulation have not been described ."}1156{"id": "1155", "text": "Using a competitive binding whole cell assay , we have examined the binding of [ 3H ] -dexamethasone at 24 and 37 degrees C in untreated normal subjects and in healthy subjects taking various glucocorticoid preparations .", "annotated_text": "Using a competitive binding whole cell assay , we have examined the binding of [ 3H ] -dexamethasone at 24 and 37 degrees C in untreated normal subjects and in healthy subjects taking various glucocorticoid preparations ."}1157{"id": "1156", "text": "At 24 degrees C normal human lymphocytes had 6000 binding sites/cell and a dissociation constant of 4 x 10 ( -9 ) M .", "annotated_text": "At 24 degrees C <cell_type>normal human lymphocytes</cell_type> had 6000 binding sites/cell and a dissociation constant of 4 x 10 ( -9 ) M ."}1158{"id": "1157", "text": "The administration of 1 mg of dexamethasone , 5 mg of prednisone , and 37.5 mg of cortisone acetate resulted in a 30 % decrease in binding sites after 1 week with no change in binding affinity .", "annotated_text": "The administration of 1 mg of dexamethasone , 5 mg of prednisone , and 37.5 mg of cortisone acetate resulted in a 30 % decrease in binding sites after 1 week with no change in binding affinity ."}1159{"id": "1158", "text": "No changes in the number of binding sites was noted before 1 week and the diminished number persisted for 1 week after discontinuation of glucocorticoid treatment .", "annotated_text": "No changes in the number of binding sites was noted before 1 week and the diminished number persisted for 1 week after discontinuation of glucocorticoid treatment ."}1160{"id": "1159", "text": "Lymphocytes from hospitalized patients taking 40-60 mg of dexamethasone daily demonstrated the same change in number of binding sites that was seen in normal subjects taking 1 mg of dexamethasone .", "annotated_text": "<cell_type>Lymphocytes</cell_type> from hospitalized patients taking 40-60 mg of dexamethasone daily demonstrated the same change in number of binding sites that was seen in normal subjects taking 1 mg of dexamethasone ."}1161{"id": "1160", "text": "When binding assays were carried out at physiologic temperature there was the same decrease in number of binding sites after dexamethasone administration , and in addition , there was a two-fold increase in binding affinity .", "annotated_text": "When binding assays were carried out at physiologic temperature there was the same decrease in number of binding sites after dexamethasone administration , and in addition , there was a two-fold increase in binding affinity ."}1162{"id": "1161", "text": "Glucocorticoid administration results in a time-dependent decrease in the number of lymphocyte glucocorticoid binding sites that is independent of the type of glucocorticoid administered .", "annotated_text": "Glucocorticoid administration results in a time-dependent decrease in the number of lymphocyte glucocorticoid binding sites that is independent of the type of glucocorticoid administered ."}1163{"id": "1162", "text": "This is the first in vivo demonstration that glucocorticoids modulate their own receptors in man .", "annotated_text": "This is the first in vivo demonstration that glucocorticoids modulate their own receptors in man ."}1164{"id": "1163", "text": "Immunoglobulin localization in benign and malignant lesions of the human mammary gland .", "annotated_text": "Immunoglobulin localization in benign and malignant lesions of the human mammary gland ."}1165{"id": "1164", "text": "Using direct imunofluorescence , lesions from 266 human breast specimens were studied for the presence of IgA , IgM , or IgG localization .", "annotated_text": "Using direct imunofluorescence , lesions from 266 human breast specimens were studied for the presence of IgA , IgM , or IgG localization ."}1166{"id": "1165", "text": "The lesions included benign elements from 66 subcutaneous mastectomy specimens in which the absence of simultaneous breast malignancy was documented , primary breast carcinomas from 153 mastectomy specimens , and 47 biopsies containing metastatic breast cancer .", "annotated_text": "The lesions included benign elements from 66 subcutaneous mastectomy specimens in which the absence of simultaneous breast malignancy was documented , primary breast carcinomas from 153 mastectomy specimens , and 47 biopsies containing metastatic breast cancer ."}1167{"id": "1166", "text": "A statistically significant association of IgA and IgM with benign lesions was contrasted to the association of IgG with malignant lesions .", "annotated_text": "A statistically significant association of <protein>IgA</protein> and <protein>IgM</protein> with benign lesions was contrasted to the association of <protein>IgG</protein> with malignant lesions ."}1168{"id": "1167", "text": "In both primary and metastatic lesions , IgG localization was associated with estrogen-receptor-poor primary cancers as compared with estrogen-receptor-rich primary cancers .", "annotated_text": "In both primary and metastatic lesions , <protein>IgG</protein> localization was associated with estrogen-receptor-poor primary cancers as compared with estrogen-receptor-rich primary cancers ."}1169{"id": "1168", "text": "Among primary breast cancer patients , IgG localization in the tumor correlated with relative lymphopenia .", "annotated_text": "Among primary breast cancer patients , <protein>IgG</protein> localization in the tumor correlated with relative lymphopenia ."}1170{"id": "1169", "text": "A shorter disease-free interval was noted in association with IgG localization among the metastatic breast lesions .", "annotated_text": "A shorter disease-free interval was noted in association with <protein>IgG</protein> localization among the metastatic breast lesions ."}1171{"id": "1170", "text": "No statistically significant association between stage of disease and immunoglobulin presence was demonstrable .", "annotated_text": "No statistically significant association between stage of disease and immunoglobulin presence was demonstrable ."}1172{"id": "1171", "text": "Moderate-to-severe intraductal epithelial hyperplasias were more often associated with immunoglobulin G localization that were other benign lesions", "annotated_text": "Moderate-to-severe intraductal epithelial hyperplasias were more often associated with <protein>immunoglobulin G</protein> localization that were other benign lesions"}1173{"id": "1172", "text": "Correlation of steroid receptors with histologic differentiation in mammary carcinoma .", "annotated_text": "Correlation of <protein>steroid receptors</protein> with histologic differentiation in mammary carcinoma ."}1174{"id": "1173", "text": "A Singapore experience .", "annotated_text": "A Singapore experience ."}1175{"id": "1174", "text": "Cancer of the breast is the most common tumor in females in Singapore , with the rate of 20.7 per 100 , 000 per year ( 1977 estimate ) , which is predicted to increase to 29.8 per 100 , 000 women per year by 1995 .", "annotated_text": "Cancer of the breast is the most common tumor in females in Singapore , with the rate of 20.7 per 100 , 000 per year ( 1977 estimate ) , which is predicted to increase to 29.8 per 100 , 000 women per year by 1995 ."}1176{"id": "1175", "text": "A detailed histopathologic review of 50 primary breast cancer tumors analyzed for estrogen receptor ( ER ) level was carried out and a variety of morphologic features correlated with ER results to identify any factors that will improve the management and prognosis for breast cancer .", "annotated_text": "A detailed histopathologic review of 50 primary breast cancer tumors analyzed for <protein>estrogen receptor</protein> ( <protein>ER</protein> ) level was carried out and a variety of morphologic features correlated with <protein>ER</protein> results to identify any factors that will improve the management and prognosis for breast cancer ."}1177{"id": "1176", "text": "Cytosol was incubated with 3H-estradiol in the presence and absence of cold diethylstilbestrol , and bound and free hormone were separated by Dextran-coated charcoal method .", "annotated_text": "Cytosol was incubated with 3H-estradiol in the presence and absence of cold diethylstilbestrol , and bound and free hormone were separated by Dextran-coated charcoal method ."}1178{"id": "1177", "text": "Tumors binding more than 5 fmol/mg cytosol protein were classified as ER -positive .", "annotated_text": "Tumors binding more than 5 fmol/mg <protein>cytosol protein</protein> were classified as <protein>ER</protein> -positive ."}1179{"id": "1178", "text": "Progesterone receptor ( PR ) level was analyzed in some specimens with the use of a similar method .", "annotated_text": "<protein>Progesterone receptor</protein> ( <protein>PR</protein> ) level was analyzed in some specimens with the use of a similar method ."}1180{"id": "1179", "text": "Most of the patients were Chinese ( 90 % ) .", "annotated_text": "Most of the patients were Chinese ( 90 % ) ."}1181{"id": "1180", "text": "Three patients were Malays , one was Indian , and one was European in this series .", "annotated_text": "Three patients were Malays , one was Indian , and one was European in this series ."}1182{"id": "1181", "text": "Results indicated that there was strong correlation between ER level , age , and histologic grade of the tumors .", "annotated_text": "Results indicated that there was strong correlation between <protein>ER</protein> level , age , and histologic grade of the tumors ."}1183{"id": "1182", "text": "No correlation existed between absence or presence of lymph node metastases and ER .", "annotated_text": "No correlation existed between absence or presence of lymph node metastases and <protein>ER</protein> ."}1184{"id": "1183", "text": "Although there was a trend for ER -positive tumors to have a low-grade lymphocytic infiltration , the difference was not statistically significant .", "annotated_text": "Although there was a trend for <protein>ER</protein> -positive tumors to have a low-grade lymphocytic infiltration , the difference was not statistically significant ."}1185{"id": "1184", "text": "Mononuclear cells infiltrating human mammary carcinomas : immunohistochemical analysis with monoclonal antibodies .", "annotated_text": "<cell_type>Mononuclear cells</cell_type> infiltrating human mammary carcinomas : immunohistochemical analysis with <protein>monoclonal antibodies</protein> ."}1186{"id": "1185", "text": "Breast carcinomas were examined by the immunoperoxidase technique using antisera specific for lymphocyte subsets , monocytes , NK cells and major histocompatibility antigens ( HLA-A , -B , -C ; Ia-like ) .", "annotated_text": "Breast carcinomas were examined by the immunoperoxidase technique using antisera specific for <cell_type>lymphocyte subsets</cell_type> , <cell_type>monocytes</cell_type> , <cell_type>NK cells</cell_type> and <protein>major histocompatibility antigens</protein> ( <protein>HLA-A</protein> , <protein>-B</protein> , -C ; <protein>Ia-like</protein> ) ."}1187{"id": "1186", "text": "Sixty-four per cent of the patients had a moderate or strong mononuclear cell infiltration , 77 % of the patients without mononuclear cell infiltration had receptors for estrogens as compared to 51 % of the patients with infiltration .", "annotated_text": "Sixty-four per cent of the patients had a moderate or strong mononuclear cell infiltration , 77 % of the patients without <cell_type>mononuclear cell</cell_type> infiltration had receptors for estrogens as compared to 51 % of the patients with infiltration ."}1188{"id": "1187", "text": "The majority of the infiltrating mononuclear cells were T cells ; generally the OKT8 cells were predominant .", "annotated_text": "The majority of the <cell_type>infiltrating mononuclear cells</cell_type> were <cell_type>T cells</cell_type> ; generally the <cell_line>OKT8 cells</cell_line> were predominant ."}1189{"id": "1188", "text": "The Leu 3A/OKT8 cell ratio was not related to histological type , tumor size , age of the patient or presence of metastases .", "annotated_text": "The Leu 3A/OKT8 cell ratio was not related to histological type , tumor size , age of the patient or presence of metastases ."}1190{"id": "1189", "text": "Some of the T cells had the Ia antigen and were thus probably activated .", "annotated_text": "Some of the T cells had the <protein>Ia antigen</protein> and were thus probably activated ."}1191{"id": "1190", "text": "The B cells were either absent or less numerous than the T cells .", "annotated_text": "The <cell_type>B cells</cell_type> were either absent or less numerous than the T cells ."}1192{"id": "1191", "text": "There was no relation between their distribution and the various parameters studied .", "annotated_text": "There was no relation between their distribution and the various parameters studied ."}1193{"id": "1192", "text": "A few monocytes were heterogeneous according to their markers ( OKM I and acid phosphatase ) .", "annotated_text": "A few <cell_type>monocytes</cell_type> were heterogeneous according to their markers ( <protein>OKM I</protein> and acid phosphatase ) ."}1194{"id": "1193", "text": "In 6 cases only there was a strong infiltration of mononuclear cells positive for acid phosphatase .", "annotated_text": "In 6 cases only there was a strong infiltration of <cell_type>mononuclear cells</cell_type> positive for <protein>acid phosphatase</protein> ."}1195{"id": "1194", "text": "The number of the natural killer cells was also low .", "annotated_text": "The number of the <cell_type>natural killer cells</cell_type> was also low ."}1196{"id": "1195", "text": "Only a few mononuclear infiltrating cells had receptors for transferrin .", "annotated_text": "Only a few mononuclear infiltrating cells had receptors for transferrin ."}1197{"id": "1196", "text": "There was a positive correlation between the inflammatory infiltration and the presence of HLA class-I antigens on tumor cell s .", "annotated_text": "There was a positive correlation between the inflammatory infiltration and the presence of <protein>HLA class-I antigens</protein> on <cell_type>tumor cell</cell_type> s ."}1198{"id": "1197", "text": "Some of the antisera specific for lymphocyte subsets also stained the breast carcinoma cells .", "annotated_text": "Some of the antisera specific for <cell_type>lymphocyte subsets</cell_type> also stained the <cell_type>breast carcinoma cells</cell_type> ."}1199{"id": "1198", "text": "The great variations in the subsets of mononuclear cells in breast carcinomas may correspond to various systems of defense against neoplasm .", "annotated_text": "The great variations in the subsets of <cell_type>mononuclear cells</cell_type> in breast carcinomas may correspond to various systems of defense against neoplasm ."}1200{"id": "1199", "text": "A case of male pseudohermaphroditism with normal androgen receptor binding and 47 , XYY karyotype .", "annotated_text": "A case of male pseudohermaphroditism with normal <protein>androgen receptor</protein> binding and 47 , XYY karyotype ."}

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