{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ]"}
{"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 ."}
{"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 % ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ]"}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"id": "38", "text": "[ Determination of the sensitivity to glucocorticoids in vitro ]", "annotated_text": "[ Determination of the sensitivity to <protein>glucocorticoids</protein> in vitro ]"}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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> ) ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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>"}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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 ) ."}
{"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 ) ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ) ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"id": "130", "text": "Possible involvement of an inhibitory protein .", "annotated_text": "Possible involvement of an <protein>inhibitory protein</protein> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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>"}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "163", "text": "End-organ resistance to cortisol was suspected .", "annotated_text": "End-organ resistance to cortisol was suspected ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"id": "172", "text": "Granulocyte-macrophage colony-stimulating factor .", "annotated_text": "<protein>Granulocyte-macrophage colony-stimulating factor</protein> ."}
{"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> ."}
{"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> ) ."}
{"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 ) ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "184", "text": "This change was promptly corrected upon resumption of therapy .", "annotated_text": "This change was promptly corrected upon resumption of therapy ."}
{"id": "185", "text": "The number of binding sites was not significantly modified .", "annotated_text": "The number of binding sites was not significantly modified ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ) ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ) ."}
{"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> ."}
{"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> ) ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "228", "text": "Meroreceptor generation is normal .", "annotated_text": "Meroreceptor generation is normal ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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"}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ) ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "271", "text": "Amplified cDNA were sequenced by standard methods .", "annotated_text": "Amplified <dna>cDNA</dna> were sequenced by standard methods ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ]"}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ) ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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"}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ) ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "359", "text": "Prominent sex steroid metabolism in human lymphocytes .", "annotated_text": "Prominent sex steroid metabolism in <cell_type>human lymphocytes</cell_type> ."}
{"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> ."}
{"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 ) ."}
{"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> ) ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "377", "text": "Copyright 1998 Academic Press .", "annotated_text": "Copyright 1998 Academic Press ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "395", "text": "N , N-dimethyl , N'-2-amidoethyl-lipoate was synthesized .", "annotated_text": "N , N-dimethyl , N'-2-amidoethyl-lipoate was synthesized ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"id": "404", "text": "Copyright 1998 Academic Press .", "annotated_text": "Copyright 1998 Academic Press ."}
{"id": "405", "text": "Carrier identification in X-linked immunodeficiency diseases .", "annotated_text": "Carrier identification in X-linked immunodeficiency diseases ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 % ) ."}
{"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> ."}
{"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 ."}
{"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"}
{"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 ."}
{"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 % ) ."}
{"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 ) ."}
{"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 ."}
{"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 ) ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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 ) ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"id": "431", "text": "Ikaros in hemopoietic lineage determination and homeostasis .", "annotated_text": "<protein>Ikaros</protein> in hemopoietic lineage determination and homeostasis ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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>"}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"id": "446", "text": "Role of cell cycle regulation .", "annotated_text": "Role of cell cycle regulation ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "454", "text": "Epidemiology and pathogenesis of AIDS-related lymphomas .", "annotated_text": "Epidemiology and pathogenesis of AIDS-related lymphomas ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ) ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ]"}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"id": "486", "text": "Local hypoxemia and stasis trigger thrombosis .", "annotated_text": "Local hypoxemia and stasis trigger thrombosis ."}
{"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> ) ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ) ."}
{"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> ) ."}
{"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 ."}
{"id": "500", "text": "No IL-6 gene expression was observed .", "annotated_text": "No <dna>IL-6 gene</dna> expression was observed ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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"}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ) ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"id": "561", "text": "This is a US government work .", "annotated_text": "This is a US government work ."}
{"id": "562", "text": "There are no restrictions on its use .", "annotated_text": "There are no restrictions on its use ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "584", "text": "NF-kappaB activation was also inhibited by CS .", "annotated_text": "NF-kappaB activation was also inhibited by CS ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "594", "text": "The patient received combined chemotherapy but response was partial .", "annotated_text": "The patient received combined chemotherapy but response was partial ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"id": "602", "text": "Tk mRNA is induced following treatment with estrogen .", "annotated_text": "<rna>Tk mRNA</rna> is induced following treatment with estrogen ."}
{"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 ."}
{"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 ."}
{"id": "605", "text": "Copyright 1998 Elsevier Science B.V .", "annotated_text": "Copyright 1998 Elsevier Science B.V ."}
{"id": "606", "text": "All rights reserved .", "annotated_text": "All rights reserved ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"id": "620", "text": "Non-Hodgkin 's lymphoma involving bilateral breasts [ see comments ]", "annotated_text": "Non-Hodgkin 's lymphoma involving bilateral breasts [ see comments ]"}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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"}
{"id": "626", "text": "Biochemical characterization of MIP-1 alpha nuclear protein .", "annotated_text": "Biochemical characterization of <protein>MIP-1 alpha nuclear protein</protein> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"id": "646", "text": "Copyright 1998 by The American Society of Hematology .", "annotated_text": "Copyright 1998 by The American Society of Hematology ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"id": "657", "text": "Copyright 1998 Academic Press .", "annotated_text": "Copyright 1998 Academic Press ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ) ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"id": "684", "text": "Long-range transcriptional regulation of cytokine gene expression .", "annotated_text": "Long-range transcriptional regulation of cytokine gene expression ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ]"}
{"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> ) ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ]"}
{"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 ) ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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"}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ) ."}
{"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 ."}
{"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 ."}
{"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 % ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"id": "733", "text": "Copyright 1998 by The American Society of Hematology .", "annotated_text": "Copyright 1998 by The American Society of Hematology ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "746", "text": "Copyright 1998 by The American Society of Hematology .", "annotated_text": "Copyright 1998 by The American Society of Hematology ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"id": "782", "text": "Western blot analysis , and immunocytochemistry .", "annotated_text": "Western blot analysis , and immunocytochemistry ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ) ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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>"}
{"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 ."}
{"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> ."}
{"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 ) ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "824", "text": "Among family members tested , his mother also had hypercortisolemia .", "annotated_text": "Among family members tested , his mother also had hypercortisolemia ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ]"}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ] ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ] ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"id": "862", "text": "The increase was specific for glucocorticoid receptor ligands .", "annotated_text": "The increase was specific for <protein>glucocorticoid receptor</protein> ligands ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"id": "866", "text": "Binding of progestins to the glucocorticoid receptor .", "annotated_text": "Binding of progestins to the <protein>glucocorticoid receptor</protein> ."}
{"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> ."}
{"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 ."}
{"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 ) ."}
{"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 % ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"id": "889", "text": "Glucocorticoid receptors in lymphoid tumors .", "annotated_text": "<protein>Glucocorticoid receptors</protein> in lymphoid tumors ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"id": "896", "text": "[ Tumor histology and steroid receptors in breast carcinoma ]", "annotated_text": "[ Tumor histology and <protein>steroid receptors</protein> in breast carcinoma ]"}
{"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 ."}
{"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 ."}
{"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"}
{"id": "900", "text": "Aldosterone-receptor deficiency in pseudohypoaldosteronism .", "annotated_text": "<protein>Aldosterone-receptor</protein> deficiency in pseudohypoaldosteronism ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ) ."}
{"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> ) ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "937", "text": "Most of the studies published so far are phenomenological .", "annotated_text": "Most of the studies published so far are phenomenological ."}
{"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 ."}
{"id": "939", "text": "Estrogen effects in adults are reversible .", "annotated_text": "Estrogen effects in adults are reversible ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ]"}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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>"}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"id": "1013", "text": "Structure and regulation of the glucocorticoid hormone receptor .", "annotated_text": "Structure and regulation of the <protein>glucocorticoid hormone receptor</protein> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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 ) ."}
{"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 ) ."}
{"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 ) ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ) ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "1070", "text": "( ABSTRACT TRUNCATED AT 400 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 400 WORDS )"}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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. ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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"}
{"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 ."}
{"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 ) ."}
{"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> ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ] ."}
{"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 ."}
{"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 ."}
{"id": "1102", "text": "Affinity was within the normal range .", "annotated_text": "Affinity was within the normal range ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "1106", "text": "Immunological interference of high dose corticosteroids .", "annotated_text": "Immunological interference of high dose corticosteroids ."}
{"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 ."}
{"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 ."}
{"id": "1109", "text": "Lymphocyte functions will be impaired .", "annotated_text": "Lymphocyte functions will be impaired ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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> ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ) ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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"}
{"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 ."}
{"id": "1173", "text": "A Singapore experience .", "annotated_text": "A Singapore experience ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"id": "1179", "text": "Most of the patients were Chinese ( 90 % ) .", "annotated_text": "Most of the patients were Chinese ( 90 % ) ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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> ."}
{"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> ) ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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 ) ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"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 ."}
{"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> ."}
{"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 ."}
{"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 ."}
{"id": "1200", "text": "A case of male pseudohermaphroditism with 47 , XYY karyotype in blood and cutaneous fibroblasts is described .", "annotated_text": "A case of male pseudohermaphroditism with 47 , XYY karyotype in blood and <cell_type>cutaneous fibroblasts</cell_type> is described ."}
{"id": "1201", "text": "The plasma testosterone response to HCG stimulation was slightly below the normal range on two occasions suggesting a deficit of gonadal function .", "annotated_text": "The plasma testosterone response to HCG stimulation was slightly below the normal range on two occasions suggesting a deficit of gonadal function ."}
{"id": "1202", "text": "A study of the receptors for dihydrotestosterone in fibroblasts of genital and nongenital skin showed a normal concentration of receptors in genital skin ; 5-alpha-reductase activity in fibroblasts of the genital skin was low , but the plasma relationship testosterone/dihydrotestosterone under HCG stimulation was normal .", "annotated_text": "A study of the receptors for dihydrotestosterone in <cell_type>fibroblasts</cell_type> of genital and nongenital skin showed a normal concentration of receptors in genital skin ; <protein>5-alpha-reductase</protein> activity in <cell_type>fibroblasts</cell_type> of the genital skin was low , but the plasma relationship testosterone/dihydrotestosterone under HCG stimulation was normal ."}
{"id": "1203", "text": "The diagnostic possibility of a complete testicular feminization syndrome with normal receptors for dihydrotestosterone is commented on .", "annotated_text": "The diagnostic possibility of a complete testicular feminization syndrome with normal receptors for dihydrotestosterone is commented on ."}
{"id": "1204", "text": "1 , 25-Dihydroxyvitamin D3 inhibits antigen-induced T cell activation .", "annotated_text": "1 , 25-Dihydroxyvitamin D3 inhibits antigen-induced <cell_type>T cell</cell_type> activation ."}
{"id": "1205", "text": "The proliferative response of murine spleen and thymus cells to antigen but not to lectin was inhibited by the active metabolite of vitamin D3 , 1 , 25- ( OH ) 2D3 .", "annotated_text": "The proliferative response of <cell_type>murine spleen and thymus cells</cell_type> to <protein>antigen</protein> but not to <protein>lectin</protein> was inhibited by the active metabolite of vitamin D3 , 1 , 25- ( OH ) 2D3 ."}
{"id": "1206", "text": "To directly examine the effect of 1 , 25- ( OH ) 2D3 on T cell activation in the absence of other complicating interactions , we utilized a panel of cloned Ia-restricted T cell hybridomas that secrete IL 2 on activation by cloned Ia-bearing stimulator cells ( TA3 ) or when stimulated by mitogen .", "annotated_text": "To directly examine the effect of 1 , 25- ( OH ) 2D3 on <cell_type>T cell</cell_type> activation in the absence of other complicating interactions , we utilized a panel of cloned <cell_line>Ia-restricted T cell hybridomas</cell_line> that secrete <protein>IL 2</protein> on activation by cloned <cell_type>Ia-bearing stimulator cells</cell_type> ( <cell_type>TA3</cell_type> ) or when stimulated by mitogen ."}
{"id": "1207", "text": "Physiologic concentrations of 1 , 25- ( OH ) 2D3 ( 0.01 to 0.1 nm ) inhibited the antigen-induced secretion of IL 2 by several of these T cell hybridomas .", "annotated_text": "Physiologic concentrations of 1 , 25- ( OH ) 2D3 ( 0.01 to 0.1 nm ) inhibited the antigen-induced secretion of IL 2 by several of these <cell_line>T cell hybridomas</cell_line> ."}
{"id": "1208", "text": "This inhibition was dependent on the concentration of the free hormone and could be overcome by increasing the number of Ia-bearing stimulator cells used .", "annotated_text": "This inhibition was dependent on the concentration of the free hormone and could be overcome by increasing the number of <cell_line>Ia-bearing stimulator cells</cell_line> used ."}
{"id": "1209", "text": "Pretreatment of the T hybridoma but not the TA3 stimulator cell with 1 , 25- ( OH ) 2D3 resulted in inhibition of activation .", "annotated_text": "Pretreatment of the <cell_line>T hybridoma</cell_line> but not the <cell_line>TA3 stimulator cell</cell_line> with 1 , 25- ( OH ) 2D3 resulted in inhibition of activation ."}
{"id": "1210", "text": "These results are consistent with the finding that specific 1 , 25- ( OH ) 2D3 receptors are present on the T cell hybridomas but are lacking in TA3 cells .", "annotated_text": "These results are consistent with the finding that specific <protein>1 , 25- ( OH ) 2D3 receptors</protein> are present on the T cell hybridomas but are lacking in <cell_line>TA3 cells</cell_line> ."}
{"id": "1211", "text": "1 , 25- ( OH ) 2D3 failed , however , to inhibit the activation of the T cell hybridomas by lectin or by an anti-Thy-1 antibody .", "annotated_text": "1 , 25- ( OH ) 2D3 failed , however , to inhibit the activation of the <cell_line>T cell hybridomas</cell_line> by <protein>lectin</protein> or by an <protein>anti-Thy-1 antibody</protein> ."}
{"id": "1212", "text": "These findings suggest that 1 , 25- ( OH ) 2D3 may be interfering with early events of antigen-induced T cell activation , perhaps by hindering T cell recognition of the relevant antigen on stimulator cell surfaces .", "annotated_text": "These findings suggest that 1 , 25- ( OH ) 2D3 may be interfering with early events of antigen-induced <cell_type>T cell</cell_type> activation , perhaps by hindering <cell_type>T cell</cell_type> recognition of the relevant antigen on stimulator cell surfaces ."}
{"id": "1213", "text": "This system should prove useful in studying the molecular mechanisms by which 1 , 25- ( OH ) 2D3 acts to inhibit T cell activation and subsequent IL 2 production .", "annotated_text": "This system should prove useful in studying the molecular mechanisms by which 1 , 25- ( OH ) 2D3 acts to inhibit T cell activation and subsequent <protein>IL 2</protein> production ."}
{"id": "1214", "text": "Glucocorticoid receptors and steroid sensitivity in normal and neoplastic human lymphoid tissues : a review .", "annotated_text": "<protein>Glucocorticoid receptors</protein> and steroid sensitivity in normal and neoplastic human lymphoid tissues : a review ."}
{"id": "1215", "text": "The determination of estrogen and progesterone receptors in breast cancer has been shown to be useful in predicting the response to endocrine therapy .", "annotated_text": "The determination of <protein>estrogen and progesterone receptors</protein> in breast cancer has been shown to be useful in predicting the response to endocrine therapy ."}
{"id": "1216", "text": "Given their well-known inhibitory effects on lymphoid tissue , glucocorticoids have been used widely in the treatment of leukemia .", "annotated_text": "Given their well-known inhibitory effects on lymphoid tissue , glucocorticoids have been used widely in the treatment of leukemia ."}
{"id": "1217", "text": "Given these facts , over the last 10 years , several investigators have measured the number of glucocorticoid receptors in normal and neoplastic lymphoid tissue to see whether their number correlated with glucocorticoid responsiveness in vitro or in vivo .", "annotated_text": "Given these facts , over the last 10 years , several investigators have measured the number of <protein>glucocorticoid receptors</protein> in normal and neoplastic lymphoid tissue to see whether their number correlated with glucocorticoid responsiveness in vitro or in vivo ."}
{"id": "1218", "text": "No clear correlation could be established between the level of glucocorticoid receptor and the in vitro action of steroids in normal and neoplastic lymphoid tissue .", "annotated_text": "No clear correlation could be established between the level of <protein>glucocorticoid receptor</protein> and the in vitro action of steroids in normal and neoplastic lymphoid tissue ."}
{"id": "1219", "text": "In contrast , attempts to correlate glucocorticoid receptor levels in acute lymphocytic leukemia to in vivo steroid responsiveness and immunological type using the whole-cell-binding assay for receptor determination and selecting the patients according to age and immunological criteria have been more successful .", "annotated_text": "In contrast , attempts to correlate <protein>glucocorticoid receptor</protein> levels in acute lymphocytic leukemia to in vivo steroid responsiveness and immunological type using the whole-cell-binding assay for receptor determination and selecting the patients according to age and immunological criteria have been more successful ."}
{"id": "1220", "text": "[ Glucocorticoid receptors in normal human lymphocytes ]", "annotated_text": "[ <protein>Glucocorticoid receptors</protein> in <cell_type>normal human lymphocytes</cell_type> ]"}
{"id": "1221", "text": "Glucocorticoid ( GC ) receptors were studied in intact lymphocytes from 11 donors .", "annotated_text": "<cell_type>Glucocorticoid ( GC ) receptors</cell_type> were studied in intact <cell_type>lymphocytes</cell_type> from 11 donors ."}
{"id": "1222", "text": "GC binding parameters were found to be highly reproducible in repeated experiments with lymphocytes .", "annotated_text": "GC binding parameters were found to be highly reproducible in repeated experiments with <cell_type>lymphocytes</cell_type> ."}
{"id": "1223", "text": "It was shown that GC receptors in donors ' lymphocytes could be distributed into two different classes similarly to the pattern seen in skin fibroblasts .", "annotated_text": "It was shown that <protein>GC receptors</protein> in donors ' <cell_type>lymphocytes</cell_type> could be distributed into two different classes similarly to the pattern seen in <cell_type>skin fibroblasts</cell_type> ."}
{"id": "1224", "text": "Human lymphocytes are an adequate object for studying genetically determined variability of GC receptors and its clinical importance .", "annotated_text": "<cell_type>Human lymphocytes</cell_type> are an adequate object for studying genetically determined variability of <protein>GC receptors</protein> and its clinical importance ."}
{"id": "1225", "text": "Specific estrogen binding sites in human lymphoid cells and thymic cells .", "annotated_text": "Specific <protein>estrogen binding sites</protein> in <cell_type>human lymphoid cells</cell_type> and <cell_type>thymic cells</cell_type> ."}
{"id": "1226", "text": "The binding of estrogen in preparations of human peripheral blood mononuclear cells , as well as by splenic and thymic cells is demonstrated by three different approaches ( Dextran-coated charcoal method , whole cell assay , and gel filtration on a sepharose 4B column ) .", "annotated_text": "The binding of estrogen in preparations of <cell_type>human peripheral blood mononuclear cells ,</cell_type> as well as by <cell_type>splenic and thymic cells</cell_type> is demonstrated by three different approaches ( Dextran-coated charcoal method , whole cell assay , and gel filtration on a sepharose 4B column ) ."}
{"id": "1227", "text": "Scatchard 's analysis of [ 3H ] -moxestrol ( R2858 ) and [ 3H ] -estradiol binding proves the existence of a single class of receptor sites having a dissociation constant of 0.18-2.4 X 10 ( -9 ) M .", "annotated_text": "Scatchard 's analysis of [ 3H ] -moxestrol ( R2858 ) and [ 3H ] -estradiol binding proves the existence of a single class of <protein>receptor sites</protein> having a dissociation constant of 0.18-2.4 X 10 ( -9 ) M ."}
{"id": "1228", "text": "Physicochemical properties of the binder , including binding capacity and steroid specificity , are quite similar to those reported for the thymus of small mammalian species or human thymoma .", "annotated_text": "Physicochemical properties of the binder , including binding capacity and steroid specificity , are quite similar to those reported for the thymus of small mammalian species or human thymoma ."}
{"id": "1229", "text": "Administration of fibroblast interferon to patients with advanced breast cancer : possible effects on skin metastasis and on hormone receptors .", "annotated_text": "Administration of <protein>fibroblast interferon</protein> to patients with advanced breast cancer : possible effects on skin metastasis and on <protein>hormone receptors</protein> ."}
{"id": "1230", "text": "Eleven patients with metastasized breast cancer received 8 intramuscular injections of 6 x 10 ( 6 ) units of human fibroblast interferon over a period of 40 days .", "annotated_text": "Eleven patients with metastasized breast cancer received 8 intramuscular injections of 6 x 10 ( 6 ) units of <protein>human fibroblast interferon</protein> over a period of 40 days ."}
{"id": "1231", "text": "The injections did not cause local irritation or inflammation .", "annotated_text": "The injections did not cause local irritation or inflammation ."}
{"id": "1232", "text": "Fever occurred in only 1 of the 11 patients .", "annotated_text": "Fever occurred in only 1 of the 11 patients ."}
{"id": "1233", "text": "Although several types of metastases were monitored , only skin nodules consistently ( 10 out of 11 patients ) exhibited changes that were suggestive of a therapeutic effect of the treatment regimen : either a simple decrease in size of some nodules or central necrosis accompanied by an inflammatory reaction .", "annotated_text": "Although several types of metastases were monitored , only skin nodules consistently ( 10 out of 11 patients ) exhibited changes that were suggestive of a therapeutic effect of the treatment regimen : either a simple decrease in size of some nodules or central necrosis accompanied by an inflammatory reaction ."}
{"id": "1234", "text": "NK-activity of peripheral blood leukocytes was significantly increased after administration of the first dose ; the effect of subsequent injections was less clear .", "annotated_text": "NK-activity of <cell_type>peripheral blood leukocytes</cell_type> was significantly increased after administration of the first dose ; the effect of subsequent injections was less clear ."}
{"id": "1235", "text": "Receptors for estrogens and progestogens were increased in the tumor biopsies of 2 out of 2 and 5 out of 6 patients tested respectively .", "annotated_text": "Receptors for estrogens and progestogens were increased in the tumor biopsies of 2 out of 2 and 5 out of 6 patients tested respectively ."}
{"id": "1236", "text": "Decreased glucocorticoid receptor binding in adrenal insufficiency .", "annotated_text": "Decreased <protein>glucocorticoid receptor</protein> binding in adrenal insufficiency ."}
{"id": "1237", "text": "To examine the effect of glucocorticoid deficiency on the glucocorticoid receptor , we examine the binding of [ 3H ] dexamethasone to lymphocytes in normal subjects and patients with adrenal insufficiency before and after glucocorticoid replacement therapy .", "annotated_text": "To examine the effect of glucocorticoid deficiency on the <protein>glucocorticoid receptor</protein> , we examine the binding of [ 3H ] dexamethasone to <cell_type>lymphocytes</cell_type> in normal subjects and patients with adrenal insufficiency before and after glucocorticoid replacement therapy ."}
{"id": "1238", "text": "Using a whole cell competitive binding assay , normal human lymphocytes had 5977 +/- 1487 ( mean +/- SD ) binding sites/cell and a dissociation constant of 10 +/- 2 nM .", "annotated_text": "Using a whole cell competitive binding assay , <cell_type>normal human lymphocytes</cell_type> had 5977 +/- 1487 ( mean +/- SD ) binding sites/cell and a dissociation constant of 10 +/- 2 nM ."}
{"id": "1239", "text": "Lymphocytes from patients with untreated adrenal insufficiency had fewer binding sites ( 3364 +/-322 ) and a 2-fold increase in binding affinity ( 5.4 +/- 0.9 mM ) .", "annotated_text": "<cell_type>Lymphocytes</cell_type> from patients with untreated adrenal insufficiency had fewer <protein>binding sites</protein> ( 3364 +/-322 ) and a 2-fold increase in binding affinity ( 5.4 +/- 0.9 mM ) ."}
{"id": "1240", "text": "The administration of conventional replacement doses of cortisone acetate for 6 months caused no change in receptor number , but was associated with a decrease in binding affinity toward normal .", "annotated_text": "The administration of conventional replacement doses of cortisone acetate for 6 months caused no change in receptor number , but was associated with a decrease in binding affinity toward normal ."}
{"id": "1241", "text": "After long term glucocorticoid replacement therapy , binding parameters were similar to those in patients before treatment .", "annotated_text": "After long term glucocorticoid replacement therapy , binding parameters were similar to those in patients before treatment ."}
{"id": "1242", "text": "The physiological implications of the decreased receptor number and increased binding affinity in adrenal insufficiency remain to be elucidated .", "annotated_text": "The physiological implications of the decreased receptor number and increased binding affinity in adrenal insufficiency remain to be elucidated ."}
{"id": "1243", "text": "Glucocorticoid receptor concentrations and terminal transferase activity as indicators of prognosis in acute non-lymphocytic leukaemia .", "annotated_text": "<protein>Glucocorticoid receptor</protein> concentrations and terminal <protein>transferase</protein> activity as indicators of prognosis in acute non-lymphocytic leukaemia ."}
{"id": "1244", "text": "Activity of terminal deoxynucleotidyl transferase ( TdT ) , adenosine deaminase , and 5'nucleotidase and the cellular concentration of glucocorticoid ( dexamethasone ) receptor were determined in 25 patients with acute non-lymphocytic leukaemia .", "annotated_text": "Activity of <protein>terminal deoxynucleotidyl transferase</protein> ( <protein>TdT</protein> ) , <protein>adenosine deaminase</protein> , and <protein>5'nucleotidase</protein> and the cellular concentration of <protein>glucocorticoid ( dexamethasone ) receptor</protein> were determined in 25 patients with acute non-lymphocytic leukaemia ."}
{"id": "1245", "text": "All patients were treated according to a common protocol .", "annotated_text": "All patients were treated according to a common protocol ."}
{"id": "1246", "text": "Increased activity of TdT ( greater than 0.1 unit/microgram DNA ) was found in 11 patients .", "annotated_text": "Increased activity of <protein>TdT</protein> ( greater than 0.1 unit/microgram DNA ) was found in 11 patients ."}
{"id": "1247", "text": "This group of patients was shown to have higher remission and survival rates ( p = 0.06 ) compared with patients with low activity of TdT .", "annotated_text": "This group of patients was shown to have higher remission and survival rates ( p = 0.06 ) compared with patients with low activity of TdT ."}
{"id": "1248", "text": "The glucocorticoid receptor concentration of the leukaemic blast cells ranged from 0 to 0.94 fmol/microgram DNA .", "annotated_text": "The <protein>glucocorticoid receptor</protein> concentration of the <cell_type>leukaemic blast cells</cell_type> ranged from 0 to 0.94 fmol/microgram DNA ."}
{"id": "1249", "text": "Thirteen patients had blast cells with a glucocorticoid receptor concentration over 0.22 fmol/microgram DNA .", "annotated_text": "Thirteen patients had <cell_type>blast cells</cell_type> with a <protein>glucocorticoid receptor</protein> concentration over 0.22 fmol/microgram DNA ."}
{"id": "1250", "text": "These patients had significantly increased remission and survival rates ( p = 0.006 ) compared with those with a low receptor concentration .", "annotated_text": "These patients had significantly increased remission and survival rates ( p = 0.006 ) compared with those with a low receptor concentration ."}
{"id": "1251", "text": "This finding can not be explained by a difference in sensitivity to glucocorticoids since these were not used as therapeutic agents .", "annotated_text": "This finding can not be explained by a difference in sensitivity to glucocorticoids since these were not used as therapeutic agents ."}
{"id": "1252", "text": "Adenosine deaminase and 5'nucleotidase activities both varied within two orders of magnitude .", "annotated_text": "<protein>Adenosine deaminase</protein> and <protein>5'nucleotidase</protein> activities both varied within two orders of magnitude ."}
{"id": "1253", "text": "No correlation could be found between activities of these enzymes and remission or survival rate .", "annotated_text": "No correlation could be found between activities of these enzymes and remission or survival rate ."}
{"id": "1254", "text": "These results show that measurements of TdT activity and the glucocorticoid receptor concentration yield valuable prognostic information in acute non-lymphocytic leukaemia", "annotated_text": "These results show that measurements of <protein>TdT</protein> activity and the <protein>glucocorticoid receptor</protein> concentration yield valuable prognostic information in acute non-lymphocytic leukaemia"}
{"id": "1255", "text": "[ 3H ] cortivazol : a unique high affinity ligand for the glucocorticoid receptor .", "annotated_text": "[ 3H ] cortivazol : a unique high affinity ligand for the <protein>glucocorticoid receptor</protein> ."}
{"id": "1256", "text": "Cortivazol ( CVZ ) and deacylcortivazol ( DAC ) are pyrazolosteroids with potent glucocorticoid activity .", "annotated_text": "Cortivazol ( CVZ ) and deacylcortivazol ( DAC ) are pyrazolosteroids with potent glucocorticoid activity ."}
{"id": "1257", "text": "In previous work we showed that DAC is 40-fold more potent than dexamethasone ( DEX ) in lysing leukemic lymphoblasts .", "annotated_text": "In previous work we showed that DAC is 40-fold more potent than dexamethasone ( DEX ) in lysing <cell_type>leukemic lymphoblasts</cell_type> ."}
{"id": "1258", "text": "To assess the interaction between these atypical steroids and the glucocorticoid receptor , we examined the binding of [ 3H ] CVZ to cytosol from glucocorticoid-sensitive and -resistant variants of the human leukemic cell line CEM C7 .", "annotated_text": "To assess the interaction between these atypical steroids and the <protein>glucocorticoid receptor</protein> , we examined the binding of [ 3H ] CVZ to cytosol from <cell_line>glucocorticoid-sensitive and -resistant variants</cell_line> of the <cell_line>human leukemic cell line</cell_line> <cell_line>CEM C7</cell_line> ."}
{"id": "1259", "text": "In glucocorticoid-sensitive cells [ 3H ] CVZ causes a 2-fold induction of glutamine synthetase and binds to a protein in the 4.6 S region of high salt sucrose gradients .", "annotated_text": "In <cell_line>glucocorticoid-sensitive cells</cell_line> [ 3H ] CVZ causes a 2-fold induction of <protein>glutamine synthetase</protein> and binds to a protein in the 4.6 S region of high salt sucrose gradients ."}
{"id": "1260", "text": "On DEAE-cellulose chromatography , [ 3H ] CVZ-receptor complexes show a shift from high ( 0.25 M KP ) to low salt ( 0.09 M KP ) eluting forms upon activation .", "annotated_text": "On DEAE-cellulose chromatography , <protein>[ 3H ] CVZ-receptor complexes</protein> show a shift from high ( 0.25 M KP ) to low salt ( 0.09 M KP ) eluting forms upon activation ."}
{"id": "1261", "text": "CVZ competes for a 97 , 000-dalton protein labeled by [ 3H ] dexamethasone mesylate .", "annotated_text": "CVZ competes for a 97 , 000-dalton protein labeled by [ 3H ] dexamethasone mesylate ."}
{"id": "1262", "text": "Scatchard analysis of the binding of [ 3H ] CVZ in glucocorticoid-sensitive cells revealed a curvilinear plot which resolved into high ( 0.4 nM ) and low ( 11 nM ) affinity components .", "annotated_text": "Scatchard analysis of the binding of [ 3H ] CVZ in <cell_line>glucocorticoid-sensitive cells</cell_line> revealed a curvilinear plot which resolved into high ( 0.4 nM ) and low ( 11 nM ) affinity components ."}
{"id": "1263", "text": "The receptor concentration of the low affinity site ( 0.30 pmol/mg protein ) was approximately twice that of the high affinity site ( 0.14 pmol/mg protein ) .", "annotated_text": "The receptor concentration of the low affinity site ( 0.30 pmol/mg protein ) was approximately twice that of the <protein>high affinity site</protein> ( 0.14 pmol/mg protein ) ."}
{"id": "1264", "text": "Dissociation experiments with dilution and/or excess unlabeled CVZ supported the presence of independent sites .", "annotated_text": "Dissociation experiments with dilution and/or excess unlabeled CVZ supported the presence of independent sites ."}
{"id": "1265", "text": "In contrast , the binding of [ 3H ] DEX to C7 cytosol revealed a single class of binding sites ( Kd = 1.9 nM ; receptor concentration , 0.46 pmol/mg protein ) .", "annotated_text": "In contrast , the binding of [ 3H ] DEX to C7 cytosol revealed a single class of binding sites ( Kd = 1.9 nM ; receptor concentration , 0.46 pmol/mg protein ) ."}
{"id": "1266", "text": "Examination of the binding of [ 3H ] CVZ using 10 ( -5 ) M DEX as the competing ligand showed that DEX binds only to the low affinity site detected by [ 3H ] CVZ .", "annotated_text": "Examination of the binding of [ 3H ] CVZ using 10 ( -5 ) M DEX as the competing ligand showed that DEX binds only to the low affinity site detected by [ 3H ] CVZ ."}
{"id": "1267", "text": "In cytosol from a glucocorticoid-resistant cell line with virtually no [ 3H ] DEX binding , [ 3H ] CVZ detected a single high affinity binding site that was similar in dissociation constant ( 0.8 nM ) and receptor concentration ( 0.13 pmol/mg protein ) to the high affinity site detected in the glucocorticoid-sensitive cell line C7 .", "annotated_text": "In cytosol from a <cell_line>glucocorticoid-resistant cell line</cell_line> with virtually no [ 3H ] DEX binding , [ 3H ] CVZ detected a single <protein>high affinity binding site</protein> that was similar in dissociation constant ( 0.8 nM ) and receptor concentration ( 0.13 pmol/mg protein ) to the <protein>high affinity site</protein> detected in the <cell_line>glucocorticoid-sensitive cell line</cell_line> <cell_line>C7</cell_line> ."}
{"id": "1268", "text": "A controlled pore glass bead assay for the measurement of cytoplasmic and nuclear glucocorticoid receptors .", "annotated_text": "A controlled pore glass bead assay for the measurement of <protein>cytoplasmic and nuclear glucocorticoid receptors</protein> ."}
{"id": "1269", "text": "An assay for the quantitation of cytoplasmic and nuclear glucocorticoid receptors in lymphoid tissue has been developed using controlled pore glass ( CPG ) beads .", "annotated_text": "An assay for the quantitation of <protein>cytoplasmic and nuclear glucocorticoid receptors</protein> in lymphoid tissue has been developed using controlled pore glass ( CPG ) beads ."}
{"id": "1270", "text": "Soluble receptor -- 3H-steroid complex ( cytosol or nuclear extract ) is adsorbed quantitatively within the crevasses of porous glass beads .", "annotated_text": "Soluble <protein>receptor -- 3H-steroid complex</protein> ( cytosol or nuclear extract ) is adsorbed quantitatively within the crevasses of porous glass beads ."}
{"id": "1271", "text": "Excess labeled steroid as well as most non-specifically bound steroid is easily washed away , leaving the hormone-receptor complex retained by the beads .", "annotated_text": "Excess labeled steroid as well as most non-specifically bound steroid is easily washed away , leaving the <protein>hormone-receptor complex</protein> retained by the beads ."}
{"id": "1272", "text": "Bound 3H-steroid is eluted with ethanol and measured for radioactivity .", "annotated_text": "Bound 3H-steroid is eluted with ethanol and measured for radioactivity ."}
{"id": "1273", "text": "This procedure which is simple , rapid , and highly reproducible is carried out using frozen samples ( stable for many months ) containing as few as 1 X 10 ( 7 ) cells .", "annotated_text": "This procedure which is simple , rapid , and highly reproducible is carried out using frozen samples ( stable for many months ) containing as few as 1 X 10 ( 7 ) cells ."}
{"id": "1274", "text": "A comparison of the CPG assay to dextran coated charcoal and a whole cell assay demonstrates that CPG and dextran coated charcoal give equivalent measurements of cytosolic receptor concentration , while the CPG and whole cell assays provide equivalent values for total receptor content .", "annotated_text": "A comparison of the CPG assay to dextran coated charcoal and a whole cell assay demonstrates that CPG and dextran coated charcoal give equivalent measurements of <protein>cytosolic receptor</protein> concentration , while the CPG and whole cell assays provide equivalent values for total receptor content ."}
{"id": "1275", "text": "Plasmacytoid blast crisis in B-cell chronic lymphocytic leukemia : effect of estradiol on growth and differentiation in vitro .", "annotated_text": "Plasmacytoid blast crisis in <cell_type>B-cell</cell_type> chronic lymphocytic leukemia : effect of estradiol on growth and differentiation in vitro ."}
{"id": "1276", "text": "Evolution of a case of chronic lymphocytic leukemia ( CLL ) into blast crisis was found to be characterized by three unusual features ( 1 ) the phenotype of the emerging blast cells was that of pre-plasmacytoid cells as shown by plasma cell morphology and an immunological phenotype corresponding partially with CLL- or intermediate B-cells , partially with plasma cells ( terminal transferase - , common acute lymphocytic leukemia antigen - , Ia+ , surface immunoglobulin heavy chains - , surface kappa light chains + , intracytoplasmic immunoglobulin A+ and G+ , BA-1+ , polyclonal gammaglobulin production ) ; ( 2 ) cytogenetic analysis of spontaneous metaphases revealed that in addition to the typical CLL abnormality , trisomy 12 , in all of the cells , an additional translocation between chromosomes 14 and 17 was present in 40 % with a presumptive breakpoint on chromosome 14 ( q12-3 ) never described before ( commonly q32 ) and ( 3 ) the progression of the disease was associated with a striking increase in the expression by the transformed cells of specific binding sites for estradiol ( E2 ) due to an actual increase in total cellular receptor proteins and not to a change in receptor affinity for E2 .", "annotated_text": "Evolution of a case of chronic lymphocytic leukemia ( CLL ) into blast crisis was found to be characterized by three unusual features ( 1 ) the phenotype of the <cell_type>emerging blast cells</cell_type> was that of <cell_type>pre-plasmacytoid cells</cell_type> as shown by plasma cell morphology and an immunological phenotype corresponding partially with <cell_type>CLL- or intermediate B-cells</cell_type> , partially with <cell_type>plasma cells</cell_type> ( <protein>terminal transferase</protein> - , common <protein>acute lymphocytic leukemia antigen</protein> - , <protein>Ia+</protein> , <protein>surface immunoglobulin heavy chains</protein> - , <protein>surface kappa light chains</protein> + , <protein>intracytoplasmic immunoglobulin A+ and G+</protein> , <protein>BA-1+</protein> , polyclonal gammaglobulin production ) ; ( 2 ) cytogenetic analysis of spontaneous metaphases revealed that in addition to the typical CLL abnormality , trisomy 12 , in all of the cells , an additional translocation between <dna>chromosomes 14 and 17</dna> was present in 40 % with a presumptive breakpoint on <dna>chromosome 14</dna> ( q12-3 ) never described before ( commonly q32 ) and ( 3 ) the progression of the disease was associated with a striking increase in the expression by the <cell_type>transformed cells</cell_type> of specific binding sites for estradiol ( E2 ) due to an actual increase in total <protein>cellular receptor proteins</protein> and not to a change in receptor affinity for E2 ."}
{"id": "1277", "text": "The functional status of the steroid receptors was confirmed by nuclear transfer of the cytoplasmic hormone-receptor complex upon temperature activation .", "annotated_text": "The functional status of the <protein>steroid receptors</protein> was confirmed by nuclear transfer of the <protein>cytoplasmic hormone-receptor complex</protein> upon temperature activation ."}
{"id": "1278", "text": "Since the rise in E2-receptor display paralleled a large increase in the proliferative activity of the cells as well as a change in their maturation status the question was raised as to whether the E2-receptor should be considered as a physiological marker of growth rate or of cellular differentiation .", "annotated_text": "Since the rise in <protein>E2-receptor</protein> display paralleled a large increase in the proliferative activity of the cells as well as a change in their maturation status the question was raised as to whether the <protein>E2-receptor</protein> should be considered as a physiological marker of growth rate or of cellular differentiation ."}
{"id": "1279", "text": "Exposure of the patient 's blast cells to E2 in vitro resulted in cessation of cell growth following at least one mitosis after addition of the inducer as seen from the replacement of the large blasts by small CLL-like cells without definite signs of alteration of the differentiation status .", "annotated_text": "Exposure of the patient 's <cell_type>blast cells</cell_type> to E2 in vitro resulted in cessation of cell growth following at least one mitosis after addition of the inducer as seen from the replacement of the <cell_type>large blasts</cell_type> by small <cell_type>CLL-like cells</cell_type> without definite signs of alteration of the differentiation status ."}
{"id": "1280", "text": "This suggests the association of E2-receptor expression with control of growth rather than cell maturation .", "annotated_text": "This suggests the association of <protein>E2-receptor</protein> expression with control of growth rather than cell maturation ."}
{"id": "1281", "text": "Multiple forms and fragments of cytosolic glucocorticoid receptors from human leukemic cells and normal lymphocytes .", "annotated_text": "Multiple forms and fragments of <protein>cytosolic glucocorticoid receptors</protein> from <cell_type>human leukemic cells</cell_type> and <cell_type>normal lymphocytes</cell_type> ."}
{"id": "1282", "text": "Therapy with glucocorticoids is generally more effective in acute lymphoblastic leukemia than in other types of human leukemia .", "annotated_text": "Therapy with glucocorticoids is generally more effective in acute lymphoblastic leukemia than in other types of human leukemia ."}
{"id": "1283", "text": "Previous studies , however , have not revealed any consistent relationship between clinical responsiveness and the cellular or cytosolic concentration of glucocorticoid-binding sites .", "annotated_text": "Previous studies , however , have not revealed any consistent relationship between clinical responsiveness and the cellular or cytosolic concentration of <protein>glucocorticoid-binding sites</protein> ."}
{"id": "1284", "text": "The objectives of this study were to determine whether there are intrinsic structural differences among the glucocorticoid receptors in various types of leukemic cells and normal lymphocytes and to investigate the role of endogenous peptidases in receptor degradation .", "annotated_text": "The objectives of this study were to determine whether there are intrinsic structural differences among the <protein>glucocorticoid receptors</protein> in various types of <cell_type>leukemic cells</cell_type> and <cell_type>normal lymphocytes</cell_type> and to investigate the role of <protein>endogenous peptidases</protein> in receptor degradation ."}
{"id": "1285", "text": "Cytosols were prepared from fresh or rapidly frozen leukocytes from 6 healthy adults and 35 high-risk leukemia patients ( median white blood cell count , 150 , 000 cells/microliter ; median age , 13 years ) .", "annotated_text": "Cytosols were prepared from <cell_type>fresh or rapidly frozen leukocytes</cell_type> from 6 healthy adults and 35 high-risk leukemia patients ( median white blood cell count , 150 , 000 cells/microliter ; median age , 13 years ) ."}
{"id": "1286", "text": "Receptors were labeled with [ 3H ] triamcinolone acetonide and quantitated by charcoal-dextran treatment or Sephadex LH-20 chromatography .", "annotated_text": "Receptors were labeled with [ 3H ] triamcinolone acetonide and quantitated by charcoal-dextran treatment or Sephadex LH-20 chromatography ."}
{"id": "1287", "text": "Mean and median cytosolic receptor concentrations in 12 acute lymphoblastic leukemia specimens lacking the standard B-cell or T-cell markers ( `` null cells '' ) were approximately 4-fold higher than in 23 other leukemic cell specimens .", "annotated_text": "Mean and median cytosolic receptor concentrations in 12 acute lymphoblastic leukemia specimens lacking the standard B-cell or T-cell markers ( `` null cells '' ) were approximately 4-fold higher than in 23 other <cell_type>leukemic cell specimens</cell_type> ."}
{"id": "1288", "text": "No other consistent differences in receptor content were observed .", "annotated_text": "No other consistent differences in receptor content were observed ."}
{"id": "1289", "text": "Agarose filtration and ultracentrifugation in hypotonic buffers containing 20 mM Na2MoO4 revealed complexes of similar size and shape in all clinical specimens tested and two established leukemic cell lines .", "annotated_text": "Agarose filtration and ultracentrifugation in hypotonic buffers containing 20 mM Na2MoO4 revealed complexes of similar size and shape in all clinical specimens tested and two established <cell_line>leukemic cell lines</cell_line> ."}
{"id": "1290", "text": "They had Stokes radii ( Rs ) of 8.1 +/- 0.5 ( S.D. ) nm ( n = 50 ) , sedimentation coefficients of 9.5 +/- 0.3S ( n = 40 ) , molecular weights of approximately 330 , 000 , and axial ratios ( a/b ) of approximately 12 .", "annotated_text": "They had Stokes radii ( Rs ) of 8.1 +/- 0.5 ( S.D. ) nm ( n = 50 ) , sedimentation coefficients of 9.5 +/- 0.3S ( n = 40 ) , molecular weights of approximately 330 , 000 , and axial ratios ( a/b ) of approximately 12 ."}
{"id": "1291", "text": "In hypertonic , molybdate-free buffer , these oligomeric complexes were dissociated into subunits with Rs of 5.9 +/- 0.3 nm ( n = 12 ) and a/b of 11 to 12 , as observed previously for other receptors .", "annotated_text": "In hypertonic , molybdate-free buffer , these <protein>oligomeric complexes</protein> were dissociated into subunits with Rs of 5.9 +/- 0.3 nm ( n = 12 ) and a/b of 11 to 12 , as observed previously for other receptors ."}
{"id": "1292", "text": "Fragmentation of the oligomer and the subunit was evident in some cytosols .", "annotated_text": "Fragmentation of the <protein>oligomer</protein> and the <protein>subunit</protein> was evident in some cytosols ."}
{"id": "1293", "text": "High activities of peptidases of various specificities were detected in leukemic cell cytosols , as in other cytosols , by fluorometric assays with derivatives of 7-amino-4-methylcoumarin .", "annotated_text": "High activities of <protein>peptidases</protein> of various specificities were detected in leukemic cell cytosols , as in other cytosols , by fluorometric assays with derivatives of 7-amino-4-methylcoumarin ."}
{"id": "1294", "text": "Receptor cleavage by these and other endogenous enzymes may account for previous observations of `` abnormal '' receptors in cytosols from some leukemic specimens .", "annotated_text": "Receptor cleavage by these and other <protein>endogenous enzymes</protein> may account for previous observations of `` abnormal '' receptors in cytosols from some <cell_type>leukemic specimens</cell_type> ."}
{"id": "1295", "text": "We conclude that intrinsic structural defects in the receptors are unlikely explanations for the unresponsiveness of some types of leukemia to steroid therapy .", "annotated_text": "We conclude that intrinsic structural defects in the receptors are unlikely explanations for the unresponsiveness of some types of leukemia to steroid therapy ."}
{"id": "1296", "text": "Glucocorticoid receptor number and intracellular water space .", "annotated_text": "<protein>Glucocorticoid receptor</protein> number and intracellular water space ."}
{"id": "1297", "text": "In order to elucidate the relationship between cell water content and number of glucocorticoid receptors , eleven normal and malignant lymphoid or myelomonocytic cell types originating from mouse , rat and man were investigated .", "annotated_text": "In order to elucidate the relationship between cell water content and number of <protein>glucocorticoid receptors</protein> , eleven normal and <cell_type>malignant lymphoid or myelomonocytic cell types</cell_type> originating from mouse , rat and man were investigated ."}
{"id": "1298", "text": "The cellular water space was measured with 3H2O , and glucocorticoid receptor number was measured in a whole-cell binding assay with [ 3H ] dexamethasone at 30 and 37 degrees C .", "annotated_text": "The cellular water space was measured with 3H2O , and <protein>glucocorticoid receptor</protein> number was measured in a whole-cell binding assay with [ 3H ] dexamethasone at 30 and 37 degrees C ."}
{"id": "1299", "text": "The intracellular water phase concentration of glucocorticoid receptors ( around 40 nmol/l cell water ) , and the dependence of receptor affinity on temperature were similar in normal and malignant rodent and human cells .", "annotated_text": "The intracellular water phase concentration of <protein>glucocorticoid receptors</protein> ( around 40 nmol/l cell water ) , and the dependence of receptor affinity on temperature were similar in <cell_type>normal and malignant rodent and human cells</cell_type> ."}
{"id": "1300", "text": "It is concluded that comparisons of glucocorticoid receptor levels are best made on the basis of intracellular receptor concentrations .", "annotated_text": "It is concluded that comparisons of <protein>glucocorticoid receptor</protein> levels are best made on the basis of <protein>intracellular receptor</protein> concentrations ."}
{"id": "1301", "text": "Covalent labeling of rat thymocyte and human lymphoid glucocorticoid receptor .", "annotated_text": "Covalent labeling of <cell_type>rat thymocyte</cell_type> and <protein>human lymphoid glucocorticoid receptor</protein> ."}
{"id": "1302", "text": "Lymphoid cells contain specific receptors for glucocorticoids .", "annotated_text": "<cell_type>Lymphoid cells</cell_type> contain specific <protein>receptors</protein> for glucocorticoids ."}
{"id": "1303", "text": "We have used [ 3H ] dexamethasone-21-mesylate to label covalently glucocorticoid receptors in rat thymic lymphocytes and in neoplastic cells obtained from patients with acute lymphoblastic leukemia and malignant lymphoma .", "annotated_text": "We have used [ 3H ] dexamethasone-21-mesylate to label covalently <protein>glucocorticoid receptors</protein> in <cell_type>rat thymic lymphocytes</cell_type> and in <cell_type>neoplastic cells</cell_type> obtained from patients with acute lymphoblastic leukemia and malignant lymphoma ."}
{"id": "1304", "text": "The covalently labeled glucocorticoid receptors were identified by polyacrylamide gel electrophoresis ( in the presence of 0.1 % sodium dodecyl sulfate ) .", "annotated_text": "The covalently labeled <protein>glucocorticoid receptors</protein> were identified by polyacrylamide gel electrophoresis ( in the presence of 0.1 % sodium dodecyl sulfate ) ."}
{"id": "1305", "text": "In cytosolic fractions prepared from rat thymic lymphocytes , [ 3H ] -dexamethasone-21-mesylate labels a protein ( Mr approximately equal to 95 , 000 ) which was identified as the glucocorticoid receptor by the following criteria : ( a ) labeling of this moiety is inhibited by treatment with a 100-fold molar excess of glucocorticoids , such as dexamethasone and triamcinolone acetonide ; and ( b ) the covalently labeled Mr approximately equal to 95 , 000 protein is activated ( by heating at 20 degrees for 30 min ) to a form that binds to DNA-cellulose .", "annotated_text": "In cytosolic fractions prepared from <cell_type>rat thymic lymphocytes</cell_type> , [ 3H ] -dexamethasone-21-mesylate labels a protein ( Mr approximately equal to 95 , 000 ) which was identified as the <protein>glucocorticoid receptor</protein> by the following criteria : ( a ) labeling of this moiety is inhibited by treatment with a 100-fold molar excess of glucocorticoids , such as dexamethasone and triamcinolone acetonide ; and ( b ) the covalently labeled Mr approximately equal to 95 , 000 protein is activated ( by heating at 20 degrees for 30 min ) to a form that binds to DNA-cellulose ."}
{"id": "1306", "text": "When intact thymocytes are treated with [ 3H ] dexamethasone-21-mesylate , an Mr approximately equal to 95 , 000 moiety is also labeled covalently .", "annotated_text": "When <cell_type>intact thymocytes</cell_type> are treated with [ 3H ] dexamethasone-21-mesylate , an Mr approximately equal to 95 , 000 moiety is also labeled covalently ."}
{"id": "1307", "text": "Approximately 35 % of the glucocorticoid receptors can be labeled covalently when intact thymocytes are treated with 100 nM [ 3H ] dexamethasone-21-mesylate for 30 min at 4 degrees .", "annotated_text": "Approximately 35 % of the <protein>glucocorticoid receptors</protein> can be labeled covalently when intact <cell_type>thymocytes</cell_type> are treated with 100 nM [ 3H ] dexamethasone-21-mesylate for 30 min at 4 degrees ."}
{"id": "1308", "text": "Neoplastic cells from acute lymphoblastic leukemia and malignant lymphoma were treated with [ 3H ] dexamethasone-21-mesylate .", "annotated_text": "<cell_type>Neoplastic cells</cell_type> from acute lymphoblastic leukemia and malignant lymphoma were treated with [ 3H ] dexamethasone-21-mesylate ."}
{"id": "1309", "text": "In all samples , an Mr approximately equal to 95 , 000 moiety was labeled covalently ; labeling was inhibited by excess glucocorticoid .", "annotated_text": "In all samples , an Mr approximately equal to 95 , 000 moiety was labeled covalently ; labeling was inhibited by excess glucocorticoid ."}
{"id": "1310", "text": "Smaller moieties were also identified by competition experiments ; these may represent proteolytic fragments of the Mr approximately equal to 95 , 000 receptor .", "annotated_text": "<protein>Smaller moieties</protein> were also identified by competition experiments ; these may represent <protein>proteolytic fragments</protein> of the Mr approximately equal to 95 , 000 receptor ."}
{"id": "1311", "text": "Thus , in rat and human lymphoid cells , [ 3H ] dexamethasone-21-mesylate can be used to label covalently the glucocorticoid receptor .", "annotated_text": "Thus , in <cell_type>rat and human lymphoid cells</cell_type> , [ 3H ] dexamethasone-21-mesylate can be used to label covalently the <protein>glucocorticoid receptor</protein> ."}
{"id": "1312", "text": "The association of cytosol oestrogen and progesterone receptors with histological features of breast cancer and early recurrence of disease .", "annotated_text": "The association of cytosol <protein>oestrogen and progesterone receptors</protein> with histological features of breast cancer and early recurrence of disease ."}
{"id": "1313", "text": "Two hundred and eighty-eight primary breast tumours were examined for the presence or absence of oestrogen ( REc ) and progesterone ( RPc ) receptors .", "annotated_text": "Two hundred and eighty-eight primary breast tumours were examined for the presence or absence of <protein>oestrogen ( REc ) and progesterone ( RPc ) receptors</protein> ."}
{"id": "1314", "text": "Analysis has shown a relative interdependence between the steroid receptor status of primary breast cancer and other prognostic variables such as histological grade , lymphocytic infiltration and tumour elastosis .", "annotated_text": "Analysis has shown a relative interdependence between the <protein>steroid receptor</protein> status of primary breast cancer and other prognostic variables such as histological grade , lymphocytic infiltration and tumour elastosis ."}
{"id": "1315", "text": "There were significant associations between epithelial cellularity , stromal fibrosis and the value of REc in those tumours in which the receptor was present .", "annotated_text": "There were significant associations between epithelial cellularity , stromal fibrosis and the value of <protein>REc</protein> in those tumours in which the receptor was present ."}
{"id": "1316", "text": "Cellularity and fibrosis were unrelated to the presence or absence of oestrogen receptor .", "annotated_text": "Cellularity and fibrosis were unrelated to the presence or absence of <protein>oestrogen receptor</protein> ."}
{"id": "1317", "text": "By contrast , neither the presence or absence nor the value of RPc could be related to cellularity or fibrosis .", "annotated_text": "By contrast , neither the presence or absence nor the value of <protein>RPc</protein> could be related to cellularity or fibrosis ."}
{"id": "1318", "text": "The value of REc and RPc analysis as an indicator of prognosis was examined in a sub-group of 175 patients receiving no additional treatment following mastectomy .", "annotated_text": "The value of <protein>REc</protein> and <protein>RPc</protein> analysis as an indicator of prognosis was examined in a sub-group of 175 patients receiving no additional treatment following mastectomy ."}
{"id": "1319", "text": "Overall relapse-free survival ( RFS ) was no different for those patients with receptors compared to those without them ( REc P = 0.11 , RPc P = 0.7 ) .", "annotated_text": "Overall relapse-free survival ( RFS ) was no different for those patients with receptors compared to those without them ( <protein>REc</protein> P = 0.11 , RPc P = 0.7 ) ."}
{"id": "1320", "text": "There was no difference in RFS of receptor positive and negative tumours when the axillary node status was taken into account .", "annotated_text": "There was no difference in RFS of receptor positive and negative tumours when the axillary node status was taken into account ."}
{"id": "1321", "text": "Clinical implications of glucocorticoid receptors in human leukemia .", "annotated_text": "Clinical implications of <protein>glucocorticoid receptors</protein> in human leukemia ."}
{"id": "1322", "text": "Normal lymphoid cells contain glucocorticoid receptor .", "annotated_text": "<cell_type>Normal lymphoid cells</cell_type> contain <protein>glucocorticoid receptor</protein> ."}
{"id": "1323", "text": "A variety of stimuli that activate these cells also induce increases in receptor concentration .", "annotated_text": "A variety of stimuli that activate these cells also induce increases in receptor concentration ."}
{"id": "1324", "text": "Similar glucocorticoid receptors can be detected in lymphoid cells from patients with acute lymphoblastic leukemia ( ALL ) .", "annotated_text": "Similar <protein>glucocorticoid receptors</protein> can be detected in <cell_type>lymphoid cells</cell_type> from patients with acute lymphoblastic leukemia ( ALL ) ."}
{"id": "1325", "text": "Absence of the glucocorticoid receptor ( usually found in treated patients ) predicts lack of glucocorticoid responsiveness .", "annotated_text": "Absence of the <protein>glucocorticoid receptor</protein> ( usually found in treated patients ) predicts lack of glucocorticoid responsiveness ."}
{"id": "1326", "text": "Furthermore , in our hands , glucocorticoid receptor levels correlate with the duration of complete remission in ALL ( though not in other forms of leukemia ) .", "annotated_text": "Furthermore , in our hands , <protein>glucocorticoid receptor</protein> levels correlate with the duration of complete remission in ALL ( though not in other forms of leukemia ) ."}
{"id": "1327", "text": "This association is independent of cell type , age , sex , or initial leukocyte count .", "annotated_text": "This association is independent of cell type , age , sex , or initial <cell_type>leukocyte</cell_type> count ."}
{"id": "1328", "text": "The level of receptor shows a negative correlation with increasing aggressiveness of the tumor ( null-cell leukemia greater than T-cell leukemia greater than Burkitt 's lymphoma ) .", "annotated_text": "The level of receptor shows a negative correlation with increasing aggressiveness of the tumor ( null-cell leukemia greater than T-cell leukemia greater than Burkitt 's lymphoma ) ."}
{"id": "1329", "text": "Corticosteroid-mediated immunoregulation in man .", "annotated_text": "Corticosteroid-mediated immunoregulation in man ."}
{"id": "1330", "text": "Glucocorticoids have profound and complex effects on the human immune response .", "annotated_text": "Glucocorticoids have profound and complex effects on the human immune response ."}
{"id": "1331", "text": "However , the precise mechanisms of the corticosteroid-induced immunoregulation in man have not been precisely defined .", "annotated_text": "However , the precise mechanisms of the corticosteroid-induced immunoregulation in man have not been precisely defined ."}
{"id": "1332", "text": "Intracytoplasmic corticosteroid-specific receptors appear to be an important common pathway for steroid-induced changes , but variations of receptor parameters do not account for the multifaceted effects on the immune system .", "annotated_text": "<protein>Intracytoplasmic corticosteroid-specific receptors</protein> appear to be an important common pathway for steroid-induced changes , but variations of receptor parameters do not account for the multifaceted effects on the immune system ."}
{"id": "1333", "text": "Human circulating mononuclear cells redistribute out of the intravascular compartment following treatment with corticosteroids .", "annotated_text": "<cell_type>Human circulating mononuclear cells</cell_type> redistribute out of the intravascular compartment following treatment with corticosteroids ."}
{"id": "1334", "text": "Although certain components at this redistribution phenomenon have been well-characterized , the importance of this compartmental cellular shift with respect to the mechanisms of corticosteroid-induced immunoregulation are less well-defined .", "annotated_text": "Although certain components at this redistribution phenomenon have been well-characterized , the importance of this compartmental cellular shift with respect to the mechanisms of corticosteroid-induced immunoregulation are less well-defined ."}
{"id": "1335", "text": "Recent observations that activated lymphocytes may be sensitive to the lytic effects of glucocorticoids suggest that under certain situations the elimination of selected subsets of cells may be a relevant mechanism of corticosteroid-mediated immunoregulation in man .", "annotated_text": "Recent observations that <cell_type>activated lymphocytes</cell_type> may be sensitive to the lytic effects of glucocorticoids suggest that under certain situations the elimination of selected subsets of cells may be a relevant mechanism of corticosteroid-mediated immunoregulation in man ."}
{"id": "1336", "text": "Corticosteroid-mediated effects on monocyte function may be an important mechanism of drug-induced immunoregulation in monocyte-dependent responses .", "annotated_text": "Corticosteroid-mediated effects on <cell_type>monocyte</cell_type> function may be an important mechanism of <cell_type>drug-induced immunoregulation</cell_type> in <cell_type>monocyte-dependent responses</cell_type> ."}
{"id": "1337", "text": "In some experimental conditions , corticosteroids inhibit Interleukin 1 production by monocytes .", "annotated_text": "In some experimental conditions , corticosteroids inhibit <protein>Interleukin 1</protein> production by <cell_type>monocytes</cell_type> ."}
{"id": "1338", "text": "The immunoregulatory effects of corticosteroids on lymphocyte immune responses are complex .", "annotated_text": "The immunoregulatory effects of corticosteroids on <cell_type>lymphocyte</cell_type> immune responses are complex ."}
{"id": "1339", "text": "In vitro corticosteroids appear to selectively affect early immunoregulatory events as opposed to altering an established response .", "annotated_text": "In vitro corticosteroids appear to selectively affect early immunoregulatory events as opposed to altering an established response ."}
{"id": "1340", "text": "Multiple sites of steroid-induced modulations of human B cell responses have been defined .", "annotated_text": "Multiple sites of steroid-induced modulations of <cell_type>human B cell</cell_type> responses have been defined ."}
{"id": "1341", "text": "Human lymphoid cell lines and glucocorticoids : II .", "annotated_text": "<cell_line>Human lymphoid cell lines</cell_line> and glucocorticoids : II ."}
{"id": "1342", "text": "Whole cell and cytoplasmic binding properties of lymphoblastoid , leukaemia and lymphoma lines .", "annotated_text": "Whole cell and cytoplasmic binding properties of <cell_line>lymphoblastoid , leukaemia and lymphoma lines</cell_line> ."}
{"id": "1343", "text": "The glucocorticoid binding properties of 18 human lymphoid cell lines ( HLCL ) have been investigated .", "annotated_text": "The glucocorticoid binding properties of 18 <cell_line>human lymphoid cell lines</cell_line> ( <cell_line>HLCL</cell_line> ) have been investigated ."}
{"id": "1344", "text": "The specificity of steroid binding was confirmed with various glucocorticoid agonists and antagonists .", "annotated_text": "The specificity of steroid binding was confirmed with various glucocorticoid agonists and antagonists ."}
{"id": "1345", "text": "A gradation in whole cell and cytoplasmic glucocorticoid binding capacity was observed in the different cell line types : lymphoblastoid greater than lymphoma greater than leukaemia .", "annotated_text": "A gradation in whole cell and cytoplasmic glucocorticoid binding capacity was observed in the different cell line types : <cell_line>lymphoblastoid</cell_line> greater than <cell_line>lymphoma</cell_line> greater than <cell_line>leukaemia</cell_line> ."}
{"id": "1346", "text": "The cytoplasmic receptors of leukaemia and lymphoblastoid lines appeared to contain both proteinaceous and phospholipid components .", "annotated_text": "The <protein>cytoplasmic receptors</protein> of <cell_line>leukaemia and lymphoblastoid lines</cell_line> appeared to contain both proteinaceous and phospholipid components ."}
{"id": "1347", "text": "Cytoplasmic steroid-receptor complexes exhibited a wide range of sedimentation coefficients ( 8.5-11.3S ) in low ionic strength buffer but there was no correlation with cell line type or glucocorticoid sensitivity .", "annotated_text": "<protein>Cytoplasmic steroid-receptor complexes</protein> exhibited a wide range of sedimentation coefficients ( 8.5-11.3S ) in low ionic strength buffer but there was no correlation with cell line type or glucocorticoid sensitivity ."}
{"id": "1348", "text": "Activation of these complexes by heat ( 37 degrees C ) or exposure to high ionic strength buffer ( 0.3 M NaCl ) induced nuclear binding of steroid but only complexes in high ionic strength buffer manifested changes in sedimentation coefficient .", "annotated_text": "Activation of these complexes by heat ( 37 degrees C ) or exposure to high ionic strength buffer ( 0.3 M NaCl ) induced nuclear binding of steroid but only complexes in high ionic strength buffer manifested changes in sedimentation coefficient ."}
{"id": "1349", "text": "No correlation was observed between the level or nature of glucocorticoid binding and the cytolethal or cytostatic responsiveness of HLCL to glucocorticoid treatment in vitro .", "annotated_text": "No correlation was observed between the level or nature of glucocorticoid binding and the cytolethal or cytostatic responsiveness of <cell_line>HLCL</cell_line> to glucocorticoid treatment in vitro ."}
{"id": "1350", "text": "The resistance to cytolethal effects can not be ascribed to a failure of cells to take up and bind steroid or to significant differences in the molecular species of cytoplasmic receptors present .", "annotated_text": "The resistance to cytolethal effects can not be ascribed to a failure of cells to take up and bind steroid or to significant differences in the molecular species of <protein>cytoplasmic receptors</protein> present ."}
{"id": "1351", "text": "The molecular mechanisms by which glucocorticoids achieve cytolethal responses in human lymphoid cells", "annotated_text": "The molecular mechanisms by which glucocorticoids achieve cytolethal responses in <cell_type>human lymphoid cells</cell_type>"}
{"id": "1352", "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": "<protein>CD28</protein> -mediated activation in <cell_type>CD45RA+ and CD45RO+ T cells</cell_type> : enhanced levels of reactive oxygen intermediates and <protein>c-Rel</protein> nuclear translocation in <cell_type>CD45RA+ cells</cell_type> ."}
{"id": "1353", "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 ( <protein>anti-CD3</protein> plus <protein>anti-CD28</protein> ) on the activation of <protein>NF-kappaB</protein> in <cell_type>CD45RA+ ( naive ) and CD45RO+ ( memory/effector ) T cells</cell_type> ."}
{"id": "1354", "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> ."}
{"id": "1355", "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> ."}
{"id": "1356", "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 cytoplasmic inhibitor <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 ."}
{"id": "1357", "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 CD28 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 ."}
{"id": "1358", "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> ."}
{"id": "1359", "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 ."}
{"id": "1360", "text": "Ikaros in hemopoietic lineage determination and homeostasis .", "annotated_text": "<protein>Ikaros</protein> in <cell_line>hemopoietic lineage</cell_line> determination and homeostasis ."}
{"id": "1361", "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 ."}
{"id": "1362", "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 ."}
{"id": "1363", "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 <cell_type>lymphoid cell</cell_type> fate determination and at subsequent branch points of the <cell_type>T cell</cell_type> differentiation pathway ."}
{"id": "1364", "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 dominant negative ( DN ) Ikaros mutation provide insight into a regulatory network through which <protein>Ikaros proteins</protein> exert their effects in development ."}
{"id": "1365", "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 in the production and differentiation of these populations .", "annotated_text": "In addition a comparative analysis of the <cell_type>hemopoietic stem cell</cell_type> and precursor compartment resulting from the two <protein>Ikaros</protein> mutations reveals a profound yet not absolute requirement for <protein>Ikaros</protein> in the production and differentiation of these populations ."}
{"id": "1366", "text": "Overexpression of p65 and c-Jun substitutes for B7-1 costimulation by targeting the CD28RE within the IL-2 promoter .", "annotated_text": "Overexpression of p65 and c-Jun substitutes for B7-1 costimulation by targeting the <dna>CD28RE</dna> within the <dna>IL-2 promoter</dna> ."}
{"id": "1367", "text": "The role of Rel and activation protein-1 ( AP-1 ) in IL-2 promoter activity in B7-1- and leukocyte function-associated Ag-3 ( LFA. 3 ) -costimulated T cells has been evaluated .", "annotated_text": "The role of <protein>Rel</protein> and <protein>activation protein-1</protein> ( <protein>AP-1</protein> ) in <dna>IL-2 promoter</dna> activity in <cell_type>B7-1- and leukocyte function-associated Ag-3 ( LFA. 3 ) -costimulated T cells</cell_type> has been evaluated ."}
{"id": "1368", "text": "We demonstrate that overexpression of c-Jun but not c-Fos increases IL-2 promoter activity in both B7-1- and LFA-3-costimulated Jurkat T cells .", "annotated_text": "We demonstrate that overexpression of <protein>c-Jun</protein> but not <protein>c-Fos</protein> increases <dna>IL-2 promoter</dna> activity in both <cell_type>B7-1- and LFA-3-costimulated Jurkat T cells</cell_type> ."}
{"id": "1369", "text": "Cotransfection of both c-Jun and c-Fos substitutes for B7-1 costimulation in driving an activation protein-1 response element but not for the IL-2 promoter .", "annotated_text": "Cotransfection of both c-Jun and c-Fos substitutes for B7-1 costimulation in driving an <dna>activation protein-1 response element</dna> but not for the <dna>IL-2 promoter</dna> ."}
{"id": "1370", "text": "Overexpression of Rel proteins demonstrated that p65-expressing Jurkat cells transcribed equally well a nuclear factor kappabeta reporter construct when costimulated with B7-1 or LFA-3 , but transcription of IL-2 promoter or CD28 response element ( CD28RE ) -driven reporters was superior in B7-1-costimulated cells .", "annotated_text": "Overexpression of <protein>Rel proteins</protein> demonstrated that <cell_line>p65-expressing Jurkat cells</cell_line> transcribed equally well a <dna>nuclear factor kappabeta reporter construct</dna> when costimulated with <protein>B7-1</protein> or <protein>LFA-3</protein> , but transcription of <dna>IL-2 promoter</dna> or <dna>CD28 response element ( CD28RE ) -driven reporters</dna> was superior in <cell_line>B7-1-costimulated cells</cell_line> ."}
{"id": "1371", "text": "Combined expression of c-Jun and p65 induced vigorous transcription of IL-2 promoter- and CD28RE-driven reporter constructs in both LFA-3- and B7-1-costimulated Jurkat cells .", "annotated_text": "Combined expression of <protein>c-Jun</protein> and <protein>p65</protein> induced vigorous transcription of <dna>IL-2 promoter- and CD28RE-driven reporter constructs</dna> in both <cell_type>LFA-3- and B7-1-costimulated Jurkat cells</cell_type> ."}
{"id": "1372", "text": "Mutating the CD28RE but not the upstream nuclear factor kappabeta-binding site in the IL-2 promoter reduced B7-1 -driven transcription > 90 % .", "annotated_text": "Mutating the <dna>CD28RE</dna> but not the <dna>upstream nuclear factor kappabeta-binding site</dna> in the <dna>IL-2 promoter</dna> reduced <protein>B7-1</protein> -driven transcription > 90 % ."}
{"id": "1373", "text": "The results implicates a major role of the CD28RE in the integration of p65 / c-Jun -mediated transcription within the IL-2 promoter .", "annotated_text": "The results implicates a major role of the <dna>CD28RE</dna> in the integration of <protein>p65</protein> / <protein>c-Jun</protein> -mediated transcription within the <dna>IL-2 promoter</dna> ."}
{"id": "1374", "text": "We suggest that the transition from an autocrine LFA-3 -driven immune response to a B7 -- induced paracrine immune response involves the activation of c-Jun and p65 , which target the CD28RE region of the IL-2 promoter .", "annotated_text": "We suggest that the transition from an autocrine <protein>LFA-3</protein> -driven immune response to a B7 -- induced paracrine immune response involves the activation of <protein>c-Jun</protein> and <protein>p65</protein> , which target the <dna>CD28RE</dna> region of the <dna>IL-2 promoter</dna> ."}
{"id": "1375", "text": "Defects in actin-cap formation in Vav-deficient mice implicate an actin requirement for lymphocyte signal transduction .", "annotated_text": "Defects in actin-cap formation in Vav-deficient mice implicate an actin requirement for lymphocyte signal transduction ."}
{"id": "1376", "text": "BACKGROUND : Antigen-receptor interactions on lymphocytes result in local clustering of actin , receptors and signaling molecules into an asymmetric membrane structure termed a cap .", "annotated_text": "BACKGROUND : Antigen-receptor interactions on <cell_type>lymphocytes</cell_type> result in local clustering of <protein>actin</protein> , receptors and signaling molecules into an asymmetric membrane structure termed a cap ."}
{"id": "1377", "text": "Although actin polymerization is known to be required , the mechanisms underlying cap formation are unclear .", "annotated_text": "Although actin polymerization is known to be required , the mechanisms underlying cap formation are unclear ."}
{"id": "1378", "text": "We have studied the events underlying cap formation using mice bearing a null mutation in vav ( vav -/- ) , a gene that encodes a guanine-nucleotide exchange factor for the GTPase Rac .", "annotated_text": "We have studied the events underlying cap formation using mice bearing a null mutation in <dna>vav</dna> ( <dna>vav</dna> -/- ) , a gene that encodes a <protein>guanine-nucleotide exchange factor</protein> for the <protein>GTPase Rac</protein> ."}
{"id": "1379", "text": "RESULTS : Lymphocytes from vav -/- mice failed to form T-cell receptor caps following activation and had a defective actin cytoskeleton .", "annotated_text": "RESULTS : <cell_type>Lymphocytes</cell_type> from <dna>vav</dna> -/- mice failed to form T-cell receptor caps following activation and had a defective actin cytoskeleton ."}
{"id": "1380", "text": "The vav-/- T cells were deficient in interleukin-2 ( IL-2 ) production and proliferation , and the peak of Ca2+ mobilization was reduced although of normal duration .", "annotated_text": "The <cell_type>vav-/- T cells</cell_type> were deficient in interleukin-2 ( IL-2 ) production and proliferation , and the peak of Ca2+ mobilization was reduced although of normal duration ."}
{"id": "1381", "text": "Activation of Jun N-terminal kinase or stress-activated kinase ( JNK or SAPK ) and mitogen-activated protein kinase ( MAPK ) and the induction of the transcription factor NF-ATc1 and egr-1 genes was normal .", "annotated_text": "Activation of <protein>Jun N-terminal kinase</protein> or <protein>stress-activated kinase</protein> ( <protein>JNK</protein> or <protein>SAPK</protein> ) and <protein>mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) and the induction of the <protein>transcription factor</protein> <dna>NF-ATc1 and egr-1 genes</dna> was normal ."}
{"id": "1382", "text": "Despite the reduced Ca2+ mobilization , translocation of cytoplasmic NF-ATc to the nucleus was normal , reflecting that the lower levels of Ca2+ in vav-/- cells were still sufficient to activate calcineurin .", "annotated_text": "Despite the reduced Ca2+ mobilization , translocation of <protein>cytoplasmic NF-ATc</protein> to the nucleus was normal , reflecting that the lower levels of Ca2+ in <cell_type>vav-/- cells</cell_type> were still sufficient to activate <protein>calcineurin</protein> ."}
{"id": "1383", "text": "Treatment of lymphocytes with cytochalasin D , which blocks actin polymerization , inhibited cap formation and produced defects in signaling and IL-2 transcriptional induction in response to antigen-receptor signaling that were nearly identical to those seen in vav-/- cells .", "annotated_text": "Treatment of <cell_type>lymphocytes</cell_type> with cytochalasin D , which blocks actin polymerization , inhibited cap formation and produced defects in signaling and IL-2 transcriptional induction in response to antigen-receptor signaling that were nearly identical to those seen in <cell_type>vav-/- cells</cell_type> ."}
{"id": "1384", "text": "In transfection studies , either constitutively active Vav or Rac could complement constitutively active calcineurin to activate NF-AT-dependent transcription .", "annotated_text": "In transfection studies , either constitutively active <protein>Vav</protein> or <protein>Rac</protein> could complement constitutively active <protein>calcineurin</protein> to activate NF-AT-dependent transcription ."}
{"id": "1385", "text": "CONCLUSIONS : These results indicate that Vav is required for cap formation in lymphocytes .", "annotated_text": "CONCLUSIONS : These results indicate that <protein>Vav</protein> is required for cap formation in <cell_type>lymphocytes</cell_type> ."}
{"id": "1386", "text": "Furthermore , the correlation between cap formation , IL-2 production and proliferation supports the hypothesis that an actin-dependent pathway is a source of specialized growth regulatory signals .", "annotated_text": "Furthermore , the correlation between cap formation , IL-2 production and proliferation supports the hypothesis that an actin-dependent pathway is a source of specialized growth regulatory signals ."}
{"id": "1387", "text": "CD14 -dependent activation of human endothelial cells by Bacteroides fragilis outer membrane .", "annotated_text": "<protein>CD14</protein> -dependent activation of <cell_type>human endothelial cells</cell_type> by Bacteroides fragilis outer membrane ."}
{"id": "1388", "text": "We studied the capacity of isolated Bacteriodes fragilis outer membrane , B. fragilis NCTC9343 lipopolysaccharide ( LPS ; endotoxin ) , and B. fragilis NCTC9343 capsular polysaccharides to activate human umbilical vein endothelial cell ( HUVEC ) monolayers .", "annotated_text": "We studied the capacity of isolated Bacteriodes fragilis outer membrane , B. fragilis NCTC9343 lipopolysaccharide ( LPS ; endotoxin ) , and B. fragilis NCTC9343 capsular polysaccharides to activate human umbilical vein endothelial cell ( HUVEC ) monolayers ."}
{"id": "1389", "text": "To assess HUVEC activation , E-selectin expression was measured by enzyme-linked immunosorbent assay ( ELISA ) , Northern blot analysis for E-selectin-specific mRNA , and electrophoretic gel mobility shift assay ( EMSA ) for NF-kappa B , a transcription factor necessary for E-selectin gene activation .", "annotated_text": "To assess HUVEC activation , <protein>E-selectin</protein> expression was measured by enzyme-linked immunosorbent assay ( ELISA ) , Northern blot analysis for <rna>E-selectin-specific mRNA</rna> , and electrophoretic gel mobility shift assay ( EMSA ) for <protein>NF-kappa B</protein> , a <protein>transcription factor</protein> necessary for <dna>E-selectin gene</dna> activation ."}
{"id": "1390", "text": "Exposure of HUVECs to B. fragilis outer membrane fractions , separated from other components of the B. fragilis cell wall by isopycnic , sucrose gradient centrifugation , significantly increased surface expression of E-selectin and induced functional endothelial cell -dependent leukocyte adhesion .", "annotated_text": "Exposure of <cell_type>HUVECs</cell_type> to B. fragilis outer membrane fractions , separated from other components of the B. fragilis cell wall by isopycnic , sucrose gradient centrifugation , significantly increased surface expression of <protein>E-selectin</protein> and induced functional <cell_type>endothelial cell</cell_type> -dependent leukocyte adhesion ."}
{"id": "1391", "text": "B. fragilis outer membranes induced translocation of NF-kappa B to HUVEC nuclei and accumulation of E-selectin mRNA in HUVEC cytoplasm .", "annotated_text": "B. fragilis outer membranes induced translocation of <protein>NF-kappa B</protein> to HUVEC nuclei and accumulation of <rna>E-selectin mRNA</rna> in HUVEC cytoplasm ."}
{"id": "1392", "text": "E-selectin expression induced by B. fragilis outer membranes was not blocked by polymixin B .", "annotated_text": "E-selectin expression induced by B. fragilis outer membranes was not blocked by polymixin B ."}
{"id": "1393", "text": "In contrast , E-selectin expression induced by outer membrane fractions purified from E. coli was competitively inhibited by polymixin B .", "annotated_text": "In contrast , E-selectin expression induced by outer membrane fractions purified from E. coli was competitively inhibited by polymixin B ."}
{"id": "1394", "text": "Neither purified B. fragilis LPS , a prominent constituent of the outer membrane , nor purified B. fragilis capsular polysaccharides induced HUVEC activation .", "annotated_text": "Neither purified B. fragilis LPS , a prominent constituent of the outer membrane , nor purified B. fragilis capsular polysaccharides induced HUVEC activation ."}
{"id": "1395", "text": "Two different monoclonal antibodies directed against human CD14 completely inhibited B. fragilis outer membrane-induced NF-kappa B activation , E-selectin transcription , and E-selectin surface expression .", "annotated_text": "Two different <protein>monoclonal antibodies</protein> directed against <protein>human CD14</protein> completely inhibited B. fragilis outer membrane-induced <protein>NF-kappa B</protein> activation , E-selectin transcription , and E-selectin surface expression ."}
{"id": "1396", "text": "We conclude that the outer membrane component of the B. fragilis cell wall contains a proinflammatory factor ( s ) , that is not LPS , which induces human endothelial cell activation by a soluble CD14 -dependent mechanism .", "annotated_text": "We conclude that the outer membrane component of the B. fragilis cell wall contains a proinflammatory factor ( s ) , that is not LPS , which induces <cell_type>human endothelial cell</cell_type> activation by a soluble <protein>CD14</protein> -dependent mechanism ."}
{"id": "1397", "text": "NF-kappaB protects HIV-1-infected myeloid cells from apoptosis .", "annotated_text": "<protein>NF-kappaB</protein> protects HIV-1-infected <cell_type>myeloid cells</cell_type> from apoptosis ."}
{"id": "1398", "text": "HIV-1 infection of primary monocytic cells and myeloid cell lines results in sustained NF-kappaB activation .", "annotated_text": "HIV-1 infection of <cell_type>primary monocytic cells</cell_type> and <cell_line>myeloid cell lines</cell_line> results in sustained NF-kappaB activation ."}
{"id": "1399", "text": "Recently , NF-kappaB induction has been shown to play a role in protecting cells from programmed cell death .", "annotated_text": "Recently , NF-kappaB induction has been shown to play a role in protecting cells from programmed cell death ."}
{"id": "1400", "text": "In the present study , we sought to investigate whether constitutive NF-kappaB activity in chronically HIV-1-infected promonocytic U937 ( U9-IIIB ) and myeloblastic PLB-985 ( PLB-IIIB ) cells affects apoptotic signaling .", "annotated_text": "In the present study , we sought to investigate whether constitutive <protein>NF-kappaB</protein> activity in chronically HIV-1-infected <cell_line>promonocytic U937 ( U9-IIIB ) and myeloblastic PLB-985 ( PLB-IIIB ) cells</cell_line> affects apoptotic signaling ."}
{"id": "1401", "text": "TNFalpha and cycloheximide caused infected cells to undergo apoptosis more rapidly than parental U937 and PLB-985 cells .", "annotated_text": "<protein>TNFalpha</protein> and cycloheximide caused infected cells to undergo apoptosis more rapidly than <cell_line>parental U937</cell_line> and <cell_line>PLB-985 cells</cell_line> ."}
{"id": "1402", "text": "Inhibition of TNFalpha -induced NF-kappaB activation using the antioxidant N-acetylcysteine ( NAC ) resulted in increased apoptosis in both U937 and U9-IIIB cells , while preactivation of NF-kappaB with the non-apoptotic inducer IL-1beta caused a relative decrease in apoptosis .", "annotated_text": "Inhibition of <protein>TNFalpha</protein> -induced NF-kappaB activation using the antioxidant N-acetylcysteine ( NAC ) resulted in increased apoptosis in both <cell_line>U937 and U9-IIIB cells</cell_line> , while preactivation of <protein>NF-kappaB</protein> with the <protein>non-apoptotic inducer IL-1beta</protein> caused a relative decrease in apoptosis ."}
{"id": "1403", "text": "Inhibition of constitutive NF-kappaB activity in U9-IIIB and PLB-IIIB cells also induced apoptosis , suggesting that NF-kappaB protects cells from a persistent apoptotic signal .", "annotated_text": "Inhibition of constitutive <protein>NF-kappaB</protein> activity in <cell_line>U9-IIIB and PLB-IIIB cells</cell_line> also induced apoptosis , suggesting that <cell_type>NF-kappaB protects cells</cell_type> from a persistent apoptotic signal ."}
{"id": "1404", "text": "TNFalpha plus NAC treatment resulted in a marked decrease in Bcl-2 protein levels in HIV-1-infected cells , coupled with an increase in Bax protein compared to uninfected cells , suggesting that the difference in susceptibility to TNFalpha -induced apoptosis may relate to the differences in relative levels of Bcl-2 and Bax .", "annotated_text": "<protein>TNFalpha</protein> plus NAC treatment resulted in a marked decrease in <protein>Bcl-2 protein</protein> levels in <cell_type>HIV-1-infected cells</cell_type> , coupled with an increase in <protein>Bax protein</protein> compared to uninfected cells , suggesting that the difference in susceptibility to <protein>TNFalpha</protein> -induced apoptosis may relate to the differences in relative levels of <protein>Bcl-2</protein> and <protein>Bax</protein> ."}
{"id": "1405", "text": "The protective role of NF-kappaB in blocking TNFalpha- and HIV-1-induced apoptosis was supported by studies in Jurkat T cells engineered to express IkappaB alpha repressor mutants ( TD-IkappaB ) under the control of a tetracycline-responsive promoter .", "annotated_text": "The protective role of <protein>NF-kappaB</protein> in blocking TNFalpha- and HIV-1-induced apoptosis was supported by studies in <cell_line>Jurkat T cells</cell_line> engineered to express <protein>IkappaB alpha repressor mutants</protein> ( <protein>TD-IkappaB</protein> ) under the control of a <dna>tetracycline-responsive promoter</dna> ."}
{"id": "1406", "text": "Cells underwent apoptosis in response to TNFalpha only when NF-kappaB activation was inhibited by TD-IkappaB expression .", "annotated_text": "Cells underwent apoptosis in response to <protein>TNFalpha</protein> only when NF-kappaB activation was inhibited by <protein>TD-IkappaB</protein> expression ."}
{"id": "1407", "text": "As was observed for the U9-IIIB cells , TNFalpha treatment also induced a marked decrease in Bcl-2 protein levels in TD-IkappaB expressing cells .", "annotated_text": "As was observed for the <cell_line>U9-IIIB cells</cell_line> , <protein>TNFalpha</protein> treatment also induced a marked decrease in <protein>Bcl-2 protein</protein> levels in <cell_type>TD-IkappaB expressing cells</cell_type> ."}
{"id": "1408", "text": "These experiments demonstrate that apoptotic signaling is perturbed in HIV-1-infected U9-IIIB cells and indicate that NF-kappaB activation may play an additional protective role against HIV-1-induced apoptosis in myeloid cells .", "annotated_text": "These experiments demonstrate that apoptotic signaling is perturbed in HIV-1-infected <cell_line>U9-IIIB cells</cell_line> and indicate that NF-kappaB activation may play an additional protective role against HIV-1-induced apoptosis in <cell_type>myeloid cells</cell_type> ."}
{"id": "1409", "text": "Human normal peripheral blood B-lymphocytes are deficient in DNA-dependent protein kinase activity due to the expression of a variant form of the Ku86 protein .", "annotated_text": "<cell_type>Human normal peripheral blood B-lymphocytes</cell_type> are deficient in DNA-dependent protein kinase activity due to the expression of a variant form of the <protein>Ku86 protein</protein> ."}
{"id": "1410", "text": "The heterodimeric Ku protein , which comprises a 86 kDa ( Ku86 ) amd a 70 kDa ( Ku70 ) subunits , is an abundant nuclear DNA-binding protein which binds in vitro to DNA termini without sequence specificity .", "annotated_text": "The heterodimeric <protein>Ku protein</protein> , which comprises a <protein>86 kDa ( Ku86 )</protein> amd a <protein>70 kDa ( Ku70 ) subunits</protein> , is an abundant <protein>nuclear DNA-binding protein</protein> which binds in vitro to <dna>DNA termini</dna> without sequence specificity ."}
{"id": "1411", "text": "Ku is the DNA-targeting component of the large catalytic sub-unit of the DNA-dependent protein kinase complex ( DNA-PK [ CS ] ) , that plays a critical role in mammalian double-strand break repair and lymphoid V ( D ) J recombination .", "annotated_text": "<protein>Ku</protein> is the <protein>DNA-targeting component</protein> of the large <protein>catalytic sub-unit</protein> of the <protein>DNA-dependent protein kinase complex</protein> ( <protein>DNA-PK [ CS ]</protein> ) , that plays a critical role in mammalian double-strand break repair and lymphoid V ( D ) J recombination ."}
{"id": "1412", "text": "By using electrophoretic mobility shift assays , we demonstrated that in addition to the major Ku x DNA complex usually detected in cell line extracts , a second complex with faster electrophoretic mobility was observed in normal peripheral blood lymphocytes ( PBL ) extracts .", "annotated_text": "By using electrophoretic mobility shift assays , we demonstrated that in addition to the <protein>major Ku x DNA complex</protein> usually detected in cell line extracts , a second complex with faster electrophoretic mobility was observed in normal <cell_type>peripheral blood lymphocytes</cell_type> ( <cell_type>PBL</cell_type> ) extracts ."}
{"id": "1413", "text": "The presence of this faster migrating complex was restricted to B cells among the circulating lymphocyte population .", "annotated_text": "The presence of this <protein>faster migrating complex</protein> was restricted to <cell_type>B cells</cell_type> among the <cell_type>circulating lymphocyte population</cell_type> ."}
{"id": "1414", "text": "Western blot analysis revealed that B cells express a variant form of the Ku86 protein with an apparent molecular weight of 69 kDa , and not the 86 kDa- full-length protein .", "annotated_text": "Western blot analysis revealed that <cell_type>B cells</cell_type> express a variant form of the <protein>Ku86 protein</protein> with an apparent molecular weight of 69 kDa , and not the <protein>86 kDa- full-length protein</protein> ."}
{"id": "1415", "text": "Although the heterodimer Ku70/variant-Ku86 binds to DNA-ends , this altered form of the Ku heterodimer has a decreased ability to recruit the catalytic component of the complex , DNA-PK ( CS ) , which contributes to an absence of detectable DNA-PK activity in B cells .", "annotated_text": "Although the <protein>heterodimer Ku70/variant-Ku86</protein> binds to <dna>DNA-ends</dna> , this altered form of the <protein>Ku heterodimer</protein> has a decreased ability to recruit the <protein>catalytic component</protein> of the complex , <protein>DNA-PK ( CS )</protein> , which contributes to an absence of detectable DNA-PK activity in <cell_type>B cells</cell_type> ."}
{"id": "1416", "text": "These data provide a molecular basis for the increased sensitivity of B cells to ionizing radiation and identify a new mechanism of regulation of DNA-PK activity that operates in vivo .", "annotated_text": "These data provide a molecular basis for the increased sensitivity of <cell_type>B cells</cell_type> to ionizing radiation and identify a new mechanism of regulation of DNA-PK activity that operates in vivo ."}
{"id": "1417", "text": "Co-stimulation of human peripheral blood mononuclear cells with IL-2 and anti-CD3 monoclonal antibodies induces phosphorylation of CREB .", "annotated_text": "Co-stimulation of <cell_type>human peripheral blood mononuclear cells</cell_type> with <protein>IL-2</protein> and <protein>anti-CD3 monoclonal antibodies</protein> induces phosphorylation of <protein>CREB</protein> ."}
{"id": "1418", "text": "Phosphorylation of the cAMP-response element binding protein CREB within 1 h of CD2 but not CD3 cross-linking of human PBMC was recently demonstrated .", "annotated_text": "Phosphorylation of the <protein>cAMP-response element binding protein CREB</protein> within 1 h of <protein>CD2</protein> but not <protein>CD3</protein> cross-linking of <cell_type>human PBMC</cell_type> was recently demonstrated ."}
{"id": "1419", "text": "The absence of P-CREB following CD3 cross-linking was unexpected , as other laboratories reported increased phosphorylation of CREB following CD3 cross-linking of the Jurkat lymphocyte cell line .", "annotated_text": "The absence of <protein>P-CREB</protein> following CD3 cross-linking was unexpected , as other laboratories reported increased phosphorylation of <protein>CREB</protein> following CD3 cross-linking of the <cell_line>Jurkat lymphocyte cell line</cell_line> ."}
{"id": "1420", "text": "Due to Jurkat T-cells being IL-2-independent , it was postulated that IL-2 might provide a necessary co-stimulus for phosphorylation of CREB in primary lymphocytes .", "annotated_text": "Due to <cell_line>Jurkat T-cells</cell_line> being IL-2-independent , it was postulated that <protein>IL-2</protein> might provide a necessary co-stimulus for phosphorylation of <protein>CREB</protein> in <cell_type>primary lymphocytes</cell_type> ."}
{"id": "1421", "text": "Therefore , P-CREB was evaluated following co-stimulation of human PBMC through the IL-2 and CD2 or CD3 receptors .", "annotated_text": "Therefore , <protein>P-CREB</protein> was evaluated following co-stimulation of <cell_type>human PBMC</cell_type> through the <protein>IL-2 and CD2 or CD3 receptors</protein> ."}
{"id": "1422", "text": "IL-2 did not further augment phosphorylation of CREB following CD2 cross-linking .", "annotated_text": "<protein>IL-2</protein> did not further augment phosphorylation of <protein>CREB</protein> following CD2 cross-linking ."}
{"id": "1423", "text": "However , while neither IL-2 nor CD3 cross-linking alone induced P-CREB , a 4.5-fold increase in phosphorylation of CREB within 1 h of IL-2/CD3 co-stimulation was observed .", "annotated_text": "However , while neither <protein>IL-2</protein> nor CD3 cross-linking alone induced <protein>P-CREB</protein> , a 4.5-fold increase in phosphorylation of <protein>CREB</protein> within 1 h of IL-2/CD3 co-stimulation was observed ."}
{"id": "1424", "text": "Phosphorylation was not associated with the induction of cAMP , and inhibition of PKA signaling had no effect on P-CREB .", "annotated_text": "Phosphorylation was not associated with the induction of cAMP , and inhibition of PKA signaling had no effect on <protein>P-CREB</protein> ."}
{"id": "1425", "text": "Consistent with signal transduction through p56lck or p59fyn , inhibition of PTK signaling reduced phosphorylation 50 % .", "annotated_text": "Consistent with signal transduction through <protein>p56lck</protein> or <protein>p59fyn</protein> , inhibition of PTK signaling reduced phosphorylation 50 % ."}
{"id": "1426", "text": "Interestingly , inhibiting PKC signaling with calphostin C further increased P-CREB levels 3-fold over that observed in IL-2/CD3 co-stimulated cells not pretreated with a PKC inhibitor .", "annotated_text": "Interestingly , inhibiting PKC signaling with calphostin C further increased P-CREB levels 3-fold over that observed in <cell_type>IL-2/CD3 co-stimulated cells</cell_type> not pretreated with a PKC inhibitor ."}
{"id": "1427", "text": "In contrast to previous studies performed in the absence of exogenous IL-2 , no increase in binding of CREB to a 32P-labeled oligonucleotide probe was observed by electrophoretic mobility shift assay .", "annotated_text": "In contrast to previous studies performed in the absence of <protein>exogenous IL-2</protein> , no increase in binding of <protein>CREB</protein> to a 32P-labeled oligonucleotide probe was observed by electrophoretic mobility shift assay ."}
{"id": "1428", "text": "These data suggest that the IL-2 and CD3 signaling pathways provide a necessary and co-operative stimulus promoting phosphorylation of CREB following receptor cross-linking .", "annotated_text": "These data suggest that the <protein>IL-2</protein> and <protein>CD3</protein> signaling pathways provide a necessary and co-operative stimulus promoting phosphorylation of <protein>CREB</protein> following receptor cross-linking ."}
{"id": "1429", "text": "HIV-1 infection induces a selective reduction in STAT5 protein expression .", "annotated_text": "HIV-1 infection induces a selective reduction in STAT5 protein expression ."}
{"id": "1430", "text": "HIV-1 infection is accompanied by qualitative and quantitative defects in CD4+ T lymphocytes .", "annotated_text": "HIV-1 infection is accompanied by qualitative and quantitative defects in <cell_type>CD4+ T lymphocytes</cell_type> ."}
{"id": "1431", "text": "Loss of immune function in HIV patients is usually associated with a profound dysregulation of cytokine production .", "annotated_text": "Loss of immune function in HIV patients is usually associated with a profound dysregulation of <protein>cytokine</protein> production ."}
{"id": "1432", "text": "To investigate whether cytokine signaling defects occur during HIV infection , PHA blasts from healthy human donors were infected with two strains of HIV-1 and screened for the expression of STAT proteins used in cytokine signaling .", "annotated_text": "To investigate whether <protein>cytokine</protein> signaling defects occur during HIV infection , <cell_type>PHA blasts</cell_type> from healthy human donors were infected with two strains of HIV-1 and screened for the expression of <protein>STAT proteins</protein> used in <protein>cytokine</protein> signaling ."}
{"id": "1433", "text": "A selective decrease in STAT5B was seen 8 days after infection with the BZ167 dual-tropic HIV isolate , but not with the Ba-L , M-tropic strain .", "annotated_text": "A selective decrease in <protein>STAT5B</protein> was seen 8 days after infection with the BZ167 dual-tropic HIV isolate , but not with the Ba-L , M-tropic strain ."}
{"id": "1434", "text": "Based on these findings , purified T cells from HIV-infected patients in different stages of disease were also tested for STAT expression ; decreases in STAT5A , STAT5B , and STAT1alpha were observed in all patients .", "annotated_text": "Based on these findings , <cell_type>purified T cells</cell_type> from HIV-infected patients in different stages of disease were also tested for STAT expression ; decreases in <protein>STAT5A</protein> , <protein>STAT5B</protein> , and <protein>STAT1alpha</protein> were observed in all patients ."}
{"id": "1435", "text": "The reduction in STATs seen in vivo and in vitro after HIV infection may contribute to the loss of T cell function in HIV disease .", "annotated_text": "The reduction in <protein>STATs</protein> seen in vivo and in vitro after HIV infection may contribute to the loss of <cell_type>T cell</cell_type> function in HIV disease ."}
{"id": "1436", "text": "Transcription factors that regulate monocyte / macrophage differentiation .", "annotated_text": "<protein>Transcription factors</protein> that regulate <cell_type>monocyte</cell_type> / <cell_type>macrophage</cell_type> differentiation ."}
{"id": "1437", "text": "Although all the cells in an organism contain the same genetic information , differences in the cell phenotype arise from the expression of lineage-specific genes .", "annotated_text": "Although all the cells in an organism contain the same genetic information , differences in the cell phenotype arise from the expression of <dna>lineage-specific genes</dna> ."}
{"id": "1438", "text": "During myelopoiesis , external differentiating signals regulate the expression of a set of transcription factors .", "annotated_text": "During myelopoiesis , external differentiating signals regulate the expression of a set of <protein>transcription factors</protein> ."}
{"id": "1439", "text": "The combined action of these transcription factors subsequently determines the expression of myeloid-specific genes and the generation of monocytes and macrophages .", "annotated_text": "The combined action of these <protein>transcription factors</protein> subsequently determines the expression of <dna>myeloid-specific genes</dna> and the generation of <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> ."}
{"id": "1440", "text": "In particular , the transcription factor PU.1 has a critical role in this process .", "annotated_text": "In particular , the <protein>transcription factor PU.1</protein> has a critical role in this process ."}
{"id": "1441", "text": "We review the contribution of several transcription factors to the control of macrophage development", "annotated_text": "We review the contribution of several <protein>transcription factors</protein> to the control of <cell_type>macrophage</cell_type> development"}
{"id": "1442", "text": "Transcription factor LKLF is sufficient to program T cell quiescence via a c-Myc -- dependent pathway .", "annotated_text": "<protein>Transcription factor LKLF</protein> is sufficient to program T cell quiescence via a c-Myc -- dependent pathway ."}
{"id": "1443", "text": "T lymphocytes circulate in a quiescent state until they encounter cognate antigen bound to the surface of an antigen-presenting cell .", "annotated_text": "<cell_type>T lymphocytes</cell_type> circulate in a quiescent state until they encounter <protein>cognate antigen</protein> bound to the surface of an <cell_type>antigen-presenting cell</cell_type> ."}
{"id": "1444", "text": "The molecular pathways that regulate T cell quiescence remain largely unknown .", "annotated_text": "The molecular pathways that regulate T cell quiescence remain largely unknown ."}
{"id": "1445", "text": "Here we show that forced expression of the lung Kruppel-like transcription factor ( LKLF ) in Jurkat T cells is sufficient to program a quiescent phenotype characterized by decreased proliferation , reduced cell size and protein synthesis and decreased surface expression of activation markers .", "annotated_text": "Here we show that forced expression of the <protein>lung Kruppel-like transcription factor</protein> ( <protein>LKLF</protein> ) in <cell_line>Jurkat T cells</cell_line> is sufficient to program a quiescent phenotype characterized by decreased proliferation , reduced cell size and protein synthesis and decreased surface expression of activation markers ."}
{"id": "1446", "text": "Conversely , LKLF-deficient peripheral T cells produced by gene targeting showed increased proliferation , increased cell size and enhanced expression of surface activation markers in vivo .", "annotated_text": "Conversely , <cell_type>LKLF-deficient peripheral T cells</cell_type> produced by gene targeting showed increased proliferation , increased cell size and enhanced expression of surface activation markers in vivo ."}
{"id": "1447", "text": "LKLF appeared to function , at least in part , by decreasing expression of the proto-oncogene encoding c-Myc .", "annotated_text": "<protein>LKLF</protein> appeared to function , at least in part , by decreasing expression of the <dna>proto-oncogene</dna> encoding <protein>c-Myc</protein> ."}
{"id": "1448", "text": "Forced expression of LKLF was associated with markedly decreased c-Myc expression .", "annotated_text": "Forced expression of <protein>LKLF</protein> was associated with markedly decreased <protein>c-Myc</protein> expression ."}
{"id": "1449", "text": "In addition , many effects of LKLF expression were mimicked by expression of the dominant-negative MadMyc protein and rescued by overexpression of c-Myc .", "annotated_text": "In addition , many effects of <protein>LKLF</protein> expression were mimicked by expression of the <protein>dominant-negative MadMyc protein</protein> and rescued by overexpression of <protein>c-Myc</protein> ."}
{"id": "1450", "text": "Thus , LKLF is both necessary and sufficient to program quiescence in T cells and functions , in part , by negatively regulating a c-Myc -- dependent pathway .", "annotated_text": "Thus , <protein>LKLF</protein> is both necessary and sufficient to program quiescence in <cell_type>T cells</cell_type> and functions , in part , by negatively regulating a c-Myc -- dependent pathway ."}
{"id": "1451", "text": "HTLV-1 p12 ( I ) protein enhances STAT5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells .", "annotated_text": "<protein>HTLV-1 p12 ( I ) protein</protein> enhances STAT5 activation and decreases the <protein>interleukin-2</protein> requirement for proliferation of <cell_type>primary human peripheral blood mononuclear cells</cell_type> ."}
{"id": "1452", "text": "The p12 ( I ) protein , encoded by the pX open reading frame I of the human T-lymphotropic virus type 1 ( HTLV-1 ) , is a hydrophobic protein that localizes to the endoplasmic reticulum and the Golgi .", "annotated_text": "The <protein>p12 ( I ) protein</protein> , encoded by the <dna>pX open reading frame I</dna> of the human T-lymphotropic virus type 1 ( HTLV-1 ) , is a <protein>hydrophobic protein</protein> that localizes to the endoplasmic reticulum and the Golgi ."}
{"id": "1453", "text": "Although p12 ( I ) contains 4 minimal proline-rich , src homology 3-binding motifs ( PXXP ) , a characteristic commonly found in proteins involved in signaling pathways , it has not been known whether p12 ( I ) has a role in modulating intracellular signaling pathways .", "annotated_text": "Although <protein>p12 ( I )</protein> contains 4 minimal proline-rich , <protein>src homology 3-binding motifs</protein> ( <protein>PXXP</protein> ) , a characteristic commonly found in proteins involved in signaling pathways , it has not been known whether <protein>p12 ( I )</protein> has a role in modulating intracellular signaling pathways ."}
{"id": "1454", "text": "This study demonstrated that p12 ( I ) binds to the cytoplasmic domain of the interleukin-2 receptor ( IL-2R ) beta chain that is involved in the recruitment of the Jak1 and Jak3 kinases .", "annotated_text": "This study demonstrated that <protein>p12 ( I )</protein> binds to the <protein>cytoplasmic domain</protein> of the <protein>interleukin-2 receptor ( IL-2R ) beta chain</protein> that is involved in the recruitment of the <protein>Jak1 and Jak3 kinases</protein> ."}
{"id": "1455", "text": "As a result of this interaction , p12 ( I ) increases signal transducers and activators of transcription 5 ( STAT5 ) DNA binding and transcriptional activity and this effect depends on the presence of both IL-2R beta and gamma ( c ) chains and Jak3 .", "annotated_text": "As a result of this interaction , <protein>p12 ( I )</protein> increases <protein>signal transducers and activators of transcription 5</protein> ( <protein>STAT5</protein> ) DNA binding and transcriptional activity and this effect depends on the presence of both <protein>IL-2R beta and gamma ( c ) chains</protein> and <protein>Jak3</protein> ."}
{"id": "1456", "text": "Transduction of primary human peripheral blood mononuclear cells ( PBMCs ) with a human immunodeficiency virus type 1-based retroviral vector expressing p12 ( I ) also resulted in increased STAT5 phosphorylation and DNA binding .", "annotated_text": "Transduction of <cell_line>primary human peripheral blood mononuclear cells</cell_line> ( <cell_type>PBMCs</cell_type> ) with a <dna>human immunodeficiency virus type 1-based retroviral vector</dna> expressing <protein>p12 ( I )</protein> also resulted in increased <protein>STAT5</protein> phosphorylation and DNA binding ."}
{"id": "1457", "text": "However , p12 ( I ) could increase proliferation of human PBMCs only after stimulation of T-cell receptors by treatment of cells with low concentrations of alphaCD3 and alphaCD28 antibodies .", "annotated_text": "However , <protein>p12 ( I )</protein> could increase proliferation of <cell_type>human PBMCs</cell_type> only after stimulation of <protein>T-cell receptors</protein> by treatment of cells with low concentrations of <protein>alphaCD3 and alphaCD28 antibodies</protein> ."}
{"id": "1458", "text": "In addition , the proliferative advantage of p12 ( I ) -transduced PBMCs was evident mainly at low concentrations of IL-2 .", "annotated_text": "In addition , the proliferative advantage of <cell_type>p12 ( I ) -transduced PBMCs</cell_type> was evident mainly at low concentrations of <protein>IL-2</protein> ."}
{"id": "1459", "text": "Together , these data indicate that p12 ( I ) may confer a proliferative advantage on HTLV-1-infected cells in the presence of suboptimal antigen stimulation and that this event may account for the clonal proliferation of infected T cells in vivo .", "annotated_text": "Together , these data indicate that <protein>p12 ( I )</protein> may confer a proliferative advantage on <cell_type>HTLV-1-infected cells</cell_type> in the presence of suboptimal antigen stimulation and that this event may account for the clonal proliferation of <cell_type>infected T cells</cell_type> in vivo ."}
{"id": "1460", "text": "( Blood. 2001 ; 98 : 823-829 )", "annotated_text": "( Blood. 2001 ; 98 : 823-829 )"}
{"id": "1461", "text": "Single dose intranasal administration of retinal autoantigen generates a rapid accumulation and cell activation in draining lymph node and spleen : implications for tolerance therapy .", "annotated_text": "Single dose intranasal administration of <protein>retinal autoantigen</protein> generates a rapid accumulation and cell activation in draining lymph node and spleen : implications for tolerance therapy ."}
{"id": "1462", "text": "BACKGROUND/AIMS : A single intranasal delivery of retinal autoantigen suppresses effectively experimental autoimmune uveoretinitis ( EAU ) .", "annotated_text": "BACKGROUND/AIMS : A single intranasal delivery of <protein>retinal autoantigen</protein> suppresses effectively experimental autoimmune uveoretinitis ( EAU ) ."}
{"id": "1463", "text": "To further unravel underlying mechanisms the authors wished to determine , firstly , the kinetics of antigen delivery and , secondly , the early cellular responses involved in the initial stages of nasal mucosal tolerance induction .", "annotated_text": "To further unravel underlying mechanisms the authors wished to determine , firstly , the kinetics of antigen delivery and , secondly , the early cellular responses involved in the initial stages of nasal mucosal tolerance induction ."}
{"id": "1464", "text": "METHODS : Flow cytometry , cell proliferation assays , and microscopy were used to track antigen following a single , intranasal dose of Alexa-488 labelled retinal antigen .", "annotated_text": "METHODS : Flow cytometry , cell proliferation assays , and microscopy were used to track <protein>antigen</protein> following a single , intranasal dose of <protein>Alexa-488 labelled retinal antigen</protein> ."}
{"id": "1465", "text": "RESULTS : A rapid accumulation of antigen within both superficial cervical lymph nodes ( SCLN ) and spleen was observed after 30 minutes .", "annotated_text": "RESULTS : A rapid accumulation of <protein>antigen</protein> within both superficial cervical lymph nodes ( SCLN ) and spleen was observed after 30 minutes ."}
{"id": "1466", "text": "Significant proliferative responses to IRBP were elicited by 48 hours indicating that systemic priming of naive T cells to retinal antigen had occurred .", "annotated_text": "Significant proliferative responses to IRBP were elicited by 48 hours indicating that systemic priming of <cell_type>naive T cells</cell_type> to <protein>retinal antigen</protein> had occurred ."}
{"id": "1467", "text": "Cell activation was further confirmed by immunoprecipitation studies , which demonstrated phosphorylation of STAT4 but not STAT6 in both lymph nodes and spleen .", "annotated_text": "Cell activation was further confirmed by immunoprecipitation studies , which demonstrated phosphorylation of <protein>STAT4</protein> but not <protein>STAT6</protein> in both lymph nodes and spleen ."}
{"id": "1468", "text": "However , at 24 hours , STAT4 heterodimerisation with STAT 3 was only observed in spleen .", "annotated_text": "However , at 24 hours , STAT4 heterodimerisation with <protein>STAT 3</protein> was only observed in spleen ."}
{"id": "1469", "text": "CONCLUSIONS : The results provide novel evidence that following a single intranasal application rapid transfer of antigen occurs .", "annotated_text": "CONCLUSIONS : The results provide novel evidence that following a single intranasal application rapid transfer of <protein>antigen</protein> occurs ."}
{"id": "1470", "text": "Resulting T cell proliferation develops consequent to differential cell signalling in SCLN and spleen .", "annotated_text": "Resulting T cell proliferation develops consequent to differential cell signalling in SCLN and spleen ."}
{"id": "1471", "text": "Further understanding of these underlying cellular mechanisms , in particular as is inferred by the results the contribution of local versus systemic tolerance induction , may assist in strategies to clinically apply mucosal tolerance therapy successfully .", "annotated_text": "Further understanding of these underlying cellular mechanisms , in particular as is inferred by the results the contribution of local versus systemic tolerance induction , may assist in strategies to clinically apply mucosal tolerance therapy successfully ."}
{"id": "1472", "text": "Regulation of interleukin ( IL ) -18 receptor alpha chain expression on CD4 ( + ) T cells during T helper ( Th ) 1/Th2 differentiation .", "annotated_text": "Regulation of <protein>interleukin ( IL ) -18 receptor alpha chain</protein> expression on <cell_type>CD4 ( + ) T cells</cell_type> during T helper ( Th ) 1/Th2 differentiation ."}
{"id": "1473", "text": "Critical downregulatory role of IL-4 .", "annotated_text": "Critical downregulatory role of <protein>IL-4</protein> ."}
{"id": "1474", "text": "Interleukin ( IL ) -18 has been well characterized as a costimulatory factor for the induction of IL-12-mediated interferon ( IFN ) -gamma production by T helper ( Th ) 1 cells , but also can induce IL-4 production and thus facilitate the differentiation of Th2 cells .", "annotated_text": "<protein>Interleukin ( IL ) -18</protein> has been well characterized as a <protein>costimulatory factor</protein> for the induction of <protein>IL-12-mediated interferon ( IFN ) -gamma</protein> production by <cell_type>T helper ( Th ) 1 cells</cell_type> , but also can induce IL-4 production and thus facilitate the differentiation of <cell_type>Th2 cells</cell_type> ."}
{"id": "1475", "text": "To determine the mechanisms by which IL-18 might regulate these diametrically distinct immune responses , we have analyzed the role of cytokines in the regulation of IL-18 receptor alpha chain ( IL-18Ralpha ) expression .", "annotated_text": "To determine the mechanisms by which <protein>IL-18</protein> might regulate these diametrically distinct immune responses , we have analyzed the role of <protein>cytokines</protein> in the regulation of <protein>IL-18 receptor alpha chain</protein> ( <protein>IL-18Ralpha</protein> ) expression ."}
{"id": "1476", "text": "The majority of peripheral CD4 ( + ) T cells constitutively expressed the IL-18Ralpha .", "annotated_text": "The majority of <cell_type>peripheral CD4 ( + ) T cells</cell_type> constitutively expressed the <protein>IL-18Ralpha</protein> ."}
{"id": "1477", "text": "Upon antigen stimulation in the presence of IL-12 , marked enhancement of IL-18Ralpha expression was observed .", "annotated_text": "Upon antigen stimulation in the presence of <protein>IL-12</protein> , marked enhancement of <protein>IL-18Ralpha</protein> expression was observed ."}
{"id": "1478", "text": "IL-12 -mediated upregulation of IL-18Ralpha required IFN-gamma .", "annotated_text": "<protein>IL-12</protein> -mediated upregulation of <protein>IL-18Ralpha</protein> required <protein>IFN-gamma</protein> ."}
{"id": "1479", "text": "Activated CD4 ( + ) T cells that expressed low levels of IL-18Ralpha could produce IFN-gamma when stimulated with the combination of IL-12 and IL-18 , while CD4 ( + ) cells which expressed high levels of IL-18Ralpha could respond to IL-18 alone .", "annotated_text": "<cell_type>Activated CD4 ( + ) T cells</cell_type> that expressed low levels of <protein>IL-18Ralpha</protein> could produce <protein>IFN-gamma</protein> when stimulated with the combination of <protein>IL-12</protein> and <protein>IL-18</protein> , while <cell_type>CD4 ( + ) cells</cell_type> which expressed high levels of <protein>IL-18Ralpha</protein> could respond to <protein>IL-18</protein> alone ."}
{"id": "1480", "text": "In contrast , T cell stimulation in the presence of IL-4 resulted in a downregulation of IL-18Ralpha expression .", "annotated_text": "In contrast , T cell stimulation in the presence of <protein>IL-4</protein> resulted in a downregulation of <protein>IL-18Ralpha</protein> expression ."}
{"id": "1481", "text": "Both IL-4 ( -/ ) - and signal transducer and activator of transcription ( Stat ) 6 ( -/ ) - T cells expressed higher levels of IL-18Ralpha after TCR stimulation .", "annotated_text": "Both <cell_type>IL-4 ( -/ ) - and signal transducer and activator of transcription ( Stat ) 6 ( -/ ) - T cells</cell_type> expressed higher levels of <protein>IL-18Ralpha</protein> after TCR stimulation ."}
{"id": "1482", "text": "Furthermore , activated T cells from Stat6 ( -/ ) - mice produced more IFN-gamma in response to IL-18 than wild-type controls .", "annotated_text": "Furthermore , <cell_type>activated T cells</cell_type> from Stat6 ( -/ ) - mice produced more <protein>IFN-gamma</protein> in response to <protein>IL-18</protein> than wild-type controls ."}
{"id": "1483", "text": "Thus , positive/negative regulation of the IL-18Ralpha by the major inductive cytokines ( IL-12 and IL-4 ) determines the capacity of IL-18 to polarize an immune response .", "annotated_text": "Thus , positive/negative regulation of the <protein>IL-18Ralpha</protein> by the major inductive <protein>cytokines</protein> ( <protein>IL-12</protein> and <protein>IL-4</protein> ) determines the capacity of <protein>IL-18</protein> to polarize an immune response ."}
{"id": "1484", "text": "Glucocorticoid-regulated transcription factors .", "annotated_text": "<protein>Glucocorticoid-regulated transcription factors</protein> ."}
{"id": "1485", "text": "Glucocorticoids are the most effective antiinflammatory drugs used in the treatment of asthma .", "annotated_text": "Glucocorticoids are the most effective antiinflammatory drugs used in the treatment of asthma ."}
{"id": "1486", "text": "They act by binding to a specific receptor ( GR ) that , upon activation , translocates to the nucleus and either increases ( transactivates ) or decreases ( transrepresses ) gene expression .", "annotated_text": "They act by binding to a specific receptor ( <protein>GR</protein> ) that , upon activation , translocates to the nucleus and either increases ( transactivates ) or decreases ( transrepresses ) gene expression ."}
{"id": "1487", "text": "Inhibition of pro-inflammatory transcription factors such as activator protein ( AP ) -1 , signal transducers and activators of transcription ( STATs ) , nuclear factor of activated T cells ( NFAT ) and nuclear factor ( NF ) -kappa B is thought to be a major action of glucocorticoids .", "annotated_text": "Inhibition of <protein>pro-inflammatory transcription factors</protein> such as <protein>activator protein ( AP ) -1</protein> , <protein>signal transducers and activators of transcription</protein> ( <protein>STATs</protein> ) , <protein>nuclear factor of activated T cells</protein> ( <protein>NFAT</protein> ) and <protein>nuclear factor ( NF ) -kappa B</protein> is thought to be a major action of glucocorticoids ."}
{"id": "1488", "text": "Acetylation of histones allows unwinding of the local DNA structure and enables RNA polymerase II to enhance gene transcription .", "annotated_text": "Acetylation of <protein>histones</protein> allows unwinding of the <dna>local DNA structure</dna> and enables <protein>RNA polymerase II</protein> to enhance gene transcription ."}
{"id": "1489", "text": "Histone acetylation is regulated by a balance between the activity of histone acetyltransferases ( HATs ) and histone deacetylases ( HDACs ) .", "annotated_text": "Histone acetylation is regulated by a balance between the activity of <protein>histone acetyltransferases</protein> ( <protein>HATs</protein> ) and <protein>histone deacetylases</protein> ( <protein>HDACs</protein> ) ."}
{"id": "1490", "text": "GR acts as a direct inhibitor of NF-kappa B-induced HAT activity and also by recruiting HDAC2 to the NF-kappa B/HAT complex .", "annotated_text": "<protein>GR</protein> acts as a direct inhibitor of NF-kappa B-induced HAT activity and also by recruiting <protein>HDAC2</protein> to the <protein>NF-kappa B/HAT complex</protein> ."}
{"id": "1491", "text": "A sub-group of patients with glucocorticoid-insensitive asthma have an inability to induce histone acetylation in response to dexamethasone suggesting reduced expression of a GR-specific HAT .", "annotated_text": "A sub-group of patients with glucocorticoid-insensitive asthma have an inability to induce histone acetylation in response to dexamethasone suggesting reduced expression of a <protein>GR-specific HAT</protein> ."}
{"id": "1492", "text": "This suggests that pharmacological manipulation of specific histone acetylation status is a potentially useful approach for the treatment of inflammatory diseases .", "annotated_text": "This suggests that pharmacological manipulation of specific histone acetylation status is a potentially useful approach for the treatment of inflammatory diseases ."}
{"id": "1493", "text": "Identification of the precise mechanism by which activated GR recruits HDAC2 may reveal new targets for the development of drugs that may dissociate the antiinflammatory actions of glucocorticoids from their side effects that are largely due to gene induction .", "annotated_text": "Identification of the precise mechanism by which <protein>activated GR</protein> recruits <protein>HDAC2</protein> may reveal new targets for the development of drugs that may dissociate the antiinflammatory actions of glucocorticoids from their side effects that are largely due to gene induction ."}
{"id": "1494", "text": "Copyright Academic Press .", "annotated_text": "Copyright Academic Press ."}
{"id": "1495", "text": "Differential ultraviolet-B-induced immunomodulation in XPA , XPC , and CSB DNA repair-deficient mice .", "annotated_text": "Differential ultraviolet-B-induced immunomodulation in XPA , XPC , and CSB DNA repair-deficient mice ."}
{"id": "1496", "text": "Ultraviolet B irradiation has serious consequences for cellular immunity and can suppress the rejection of skin tumors and the resistance to infectious diseases .", "annotated_text": "Ultraviolet B irradiation has serious consequences for cellular immunity and can suppress the rejection of skin tumors and the resistance to infectious diseases ."}
{"id": "1497", "text": "DNA damage plays a crucial role in these immunomodulatory effects of ultraviolet B , as impaired repair of ultraviolet-B-induced DNA damage has been shown to cause suppression of cellular immunity .", "annotated_text": "DNA damage plays a crucial role in these immunomodulatory effects of ultraviolet B , as impaired repair of ultraviolet-B-induced DNA damage has been shown to cause suppression of cellular immunity ."}
{"id": "1498", "text": "Ultraviolet-B-induced DNA damage is repaired by the nucleotide excision repair mechanism very efficiently .", "annotated_text": "Ultraviolet-B-induced DNA damage is repaired by the nucleotide excision repair mechanism very efficiently ."}
{"id": "1499", "text": "Nucleotide excision repair comprises two subpathways : transcription-coupled and global genome repair .", "annotated_text": "Nucleotide excision repair comprises two subpathways : transcription-coupled and global genome repair ."}
{"id": "1500", "text": "In this study the immunologic consequences of specific nucleotide excision repair defects in three mouse models , XPA , XPC , and CSB mutant mice , were investigated .", "annotated_text": "In this study the immunologic consequences of specific nucleotide excision repair defects in three mouse models , XPA , XPC , and CSB mutant mice , were investigated ."}
{"id": "1501", "text": "XPA mice carry a total nucleotide excision repair defect , whereas XPC and CSB mice only lack global genome and transcription-coupled nucleotide excision repair , respectively .", "annotated_text": "XPA mice carry a total nucleotide excision repair defect , whereas XPC and CSB mice only lack global genome and transcription-coupled nucleotide excision repair , respectively ."}
{"id": "1502", "text": "Our data demonstrate that cellular immune parameters in XPA , XPC , and CSB mice are normal compared with their wild-type ( control ) littermates .", "annotated_text": "Our data demonstrate that cellular immune parameters in XPA , XPC , and CSB mice are normal compared with their wild-type ( control ) littermates ."}
{"id": "1503", "text": "This may indicate that the reported altered cellular responses in xeroderma pigmentosum patients are not constitutive but could be due to external factors , such as ultraviolet B .", "annotated_text": "This may indicate that the reported altered cellular responses in xeroderma pigmentosum patients are not constitutive but could be due to external factors , such as ultraviolet B ."}
{"id": "1504", "text": "Upon exposure to ultraviolet B , only XPA mice are very sensitive to ultraviolet-B-induced inhibition of Th1-mediated contact hypersensitivity responses and interferon-gamma production in skin draining lymph nodes .", "annotated_text": "Upon exposure to ultraviolet B , only XPA mice are very sensitive to ultraviolet-B-induced inhibition of Th1-mediated contact hypersensitivity responses and <protein>interferon-gamma</protein> production in skin draining lymph nodes ."}
{"id": "1505", "text": "Lipopolysaccharide-stimulated tumor necrosis factor alpha and interleukin-10 production are significantly augmented in both XPA and CSB mice after ultraviolet B exposure .", "annotated_text": "Lipopolysaccharide-stimulated <protein>tumor necrosis factor alpha</protein> and <protein>interleukin-10</protein> production are significantly augmented in both XPA and CSB mice after ultraviolet B exposure ."}
{"id": "1506", "text": "Lymph node cell numbers were increased very significantly in XPA , mildly increased in CSB , and not in XPC mice .", "annotated_text": "Lymph node cell numbers were increased very significantly in XPA , mildly increased in CSB , and not in XPC mice ."}
{"id": "1507", "text": "In general XPC mice do not exhibit any indication of enhanced ultraviolet B susceptibility with regard to the immune parameters analyzed .", "annotated_text": "In general XPC mice do not exhibit any indication of enhanced ultraviolet B susceptibility with regard to the immune parameters analyzed ."}
{"id": "1508", "text": "These data suggest that both global genome repair and transcription-coupled repair are needed to prevent immunomodulation by ultraviolet B , whereas transcription-coupled repair is the major DNA repair subpathway of nucleotide excision repair that prevents the acute ultraviolet-B-induced effects such as erythema .", "annotated_text": "These data suggest that both global genome repair and transcription-coupled repair are needed to prevent immunomodulation by ultraviolet B , whereas transcription-coupled repair is the major DNA repair subpathway of nucleotide excision repair that prevents the acute ultraviolet-B-induced effects such as erythema ."}
{"id": "1509", "text": "Biomechanical strain induces class a scavenger receptor expression in human monocyte/macrophages and THP-1 cells : a potential mechanism of increased atherosclerosis in hypertension .", "annotated_text": "Biomechanical strain induces class a <protein>scavenger receptor</protein> expression in <cell_type>human monocyte/macrophages</cell_type> and <cell_type>THP-1 cells</cell_type> : a potential mechanism of increased atherosclerosis in hypertension ."}
{"id": "1510", "text": "BACKGROUND : Although hypertension is an important risk factor for the development of atherosclerosis , the mechanisms for this interaction are incompletely described .", "annotated_text": "BACKGROUND : Although hypertension is an important risk factor for the development of atherosclerosis , the mechanisms for this interaction are incompletely described ."}
{"id": "1511", "text": "Previous studies have suggested that biomechanical strain regulates macrophage phenotype .", "annotated_text": "Previous studies have suggested that biomechanical strain regulates macrophage phenotype ."}
{"id": "1512", "text": "We tested the hypothesis that biomechanical strain can induce expression of the class A scavenger receptor ( SRA ) , an important lipoprotein receptor in atherogenesis .", "annotated_text": "We tested the hypothesis that biomechanical strain can induce expression of the <protein>class A scavenger receptor</protein> ( <protein>SRA</protein> ) , an important <protein>lipoprotein receptor</protein> in atherogenesis ."}
{"id": "1513", "text": "METHODS AND RESULTS : Human monocyte/macrophages or THP-1 cells were cultured in a device that imposes uniform biaxial cyclic 1-Hz strains of 0 % , 1 % , 2 % , or 3 % , and SRA expression was analyzed .", "annotated_text": "METHODS AND RESULTS : <cell_type>Human monocyte/macrophages</cell_type> or <cell_type>THP-1 cells</cell_type> were cultured in a device that imposes uniform biaxial cyclic 1-Hz strains of 0 % , 1 % , 2 % , or 3 % , and <protein>SRA</protein> expression was analyzed ."}
{"id": "1514", "text": "Mechanical strains induced SRA mRNA ( 3.5+/-0.6-fold at 3 % strain for 48 hours , P < 0.01 ) and SRA protein in THP-1 cells in an amplitude-dependent manner .", "annotated_text": "Mechanical strains induced <rna>SRA mRNA</rna> ( 3.5+/-0.6-fold at 3 % strain for 48 hours , P < 0.01 ) and <protein>SRA protein</protein> in <cell_type>THP-1 cells</cell_type> in an amplitude-dependent manner ."}
{"id": "1515", "text": "This induction was accompanied by augmented expression of the class B scavenger receptor CD36 ( 2.8+/-0.3-fold , P < 0.001 ) but not by increased peroxisome proliferator-activated receptor-gamma expression .", "annotated_text": "This induction was accompanied by augmented expression of the <protein>class B scavenger receptor CD36</protein> ( 2.8+/-0.3-fold , P < 0.001 ) but not by increased <protein>peroxisome proliferator-activated receptor-gamma</protein> expression ."}
{"id": "1516", "text": "To evaluate this effect in vivo , apolipoprotein E ( -/- ) mice were randomly assigned to receive standard chow , a high-cholesterol diet , or a high-cholesterol diet with hypertension induced by angiotensin II infusion for 8 weeks .", "annotated_text": "To evaluate this effect in vivo , apolipoprotein E ( -/- ) mice were randomly assigned to receive standard chow , a high-cholesterol diet , or a high-cholesterol diet with hypertension induced by angiotensin II infusion for 8 weeks ."}
{"id": "1517", "text": "Immunohistochemistry revealed that among macrophages in atherosclerotic lesions of the aorta , the proportion of macrophages with SRA expression was highest in hypertensive animals on a high-cholesterol diet ( 43.9+/-0.7 % , versus 12.0+/-2.0 % for normotensive animals on a high-cholesterol diet and 4.7+/-4.7 % for animals on standard chow ; P < 0.001 ) .", "annotated_text": "Immunohistochemistry revealed that among <cell_type>macrophages</cell_type> in atherosclerotic lesions of the aorta , the proportion of <cell_type>macrophages</cell_type> with <protein>SRA</protein> expression was highest in hypertensive animals on a high-cholesterol diet ( 43.9+/-0.7 % , versus 12.0+/-2.0 % for normotensive animals on a high-cholesterol diet and 4.7+/-4.7 % for animals on standard chow ; P < 0.001 ) ."}
{"id": "1518", "text": "CONCLUSIONS : Biomechanical strain induces SRA expression by monocyte/macrophages , suggesting a novel mechanism for promotion of atherosclerosis in hypertensive patients .", "annotated_text": "CONCLUSIONS : Biomechanical strain induces <protein>SRA</protein> expression by <cell_type>monocyte/macrophages</cell_type> , suggesting a novel mechanism for promotion of atherosclerosis in hypertensive patients ."}
{"id": "1519", "text": "High glucose induces MCP-1 expression partly via tyrosine kinase-AP-1 pathway in peritoneal mesothelial cells .", "annotated_text": "High glucose induces MCP-1 expression partly via tyrosine kinase-AP-1 pathway in <cell_type>peritoneal mesothelial cells</cell_type> ."}
{"id": "1520", "text": "BACKGROUND : High glucose in peritoneal dialysis solutions has been implicated in the pathogenesis of peritoneal fibrosis in chronic ambulatory peritoneal dialysis ( CAPD ) patients .", "annotated_text": "BACKGROUND : High glucose in peritoneal dialysis solutions has been implicated in the pathogenesis of peritoneal fibrosis in chronic ambulatory peritoneal dialysis ( CAPD ) patients ."}
{"id": "1521", "text": "However , the mechanisms are not very clear .", "annotated_text": "However , the mechanisms are not very clear ."}
{"id": "1522", "text": "Peritoneal macrophages seem to participate in the process of peritoneal fibrosis and monocyte chemoattractant protein-1 ( MCP-1 ) plays a key role in the recruitment of monocytes toward the peritoneal cavity .", "annotated_text": "<cell_type>Peritoneal macrophages</cell_type> seem to participate in the process of peritoneal fibrosis and <protein>monocyte chemoattractant protein-1</protein> ( <protein>MCP-1</protein> ) plays a key role in the recruitment of <cell_type>monocytes</cell_type> toward the peritoneal cavity ."}
{"id": "1523", "text": "However , little is known about the effect of high glucose on MCP-1 expression and its signal transduction pathway in human peritoneal mesothelial cells .", "annotated_text": "However , little is known about the effect of high glucose on <protein>MCP-1</protein> expression and its signal transduction pathway in <cell_type>human peritoneal mesothelial cells</cell_type> ."}
{"id": "1524", "text": "METHODS : Mesothelial cells were cultured with glucose ( 5 to 100 mmol/L ) or mannitol chronically for up to seven days .", "annotated_text": "METHODS : <cell_type>Mesothelial cells</cell_type> were cultured with glucose ( 5 to 100 mmol/L ) or mannitol chronically for up to seven days ."}
{"id": "1525", "text": "MCP-1 expression of mRNA and protein was measured by Northern blot analysis and enzyme-linked immunosorbent assay ( ELISA ) .", "annotated_text": "<protein>MCP-1</protein> expression of mRNA and protein was measured by Northern blot analysis and enzyme-linked immunosorbent assay ( ELISA ) ."}
{"id": "1526", "text": "Chemotactic activity of high-glucose-conditioned culture supernatant was measured by chemotactic assay .", "annotated_text": "Chemotactic activity of high-glucose-conditioned culture supernatant was measured by chemotactic assay ."}
{"id": "1527", "text": "To examine the roles of the transcription factors activator protein-1 ( AP-1 ) and nuclear factor-kappaB ( NF-kappaB ) , electrophoretic mobility shift assay ( EMSA ) was performed .", "annotated_text": "To examine the roles of the <protein>transcription factors</protein> <protein>activator protein-1</protein> ( <protein>AP-1</protein> ) and <protein>nuclear factor-kappaB</protein> ( <protein>NF-kappaB</protein> ) , electrophoretic mobility shift assay ( EMSA ) was performed ."}
{"id": "1528", "text": "RESULTS : Glucose induced MCP-1 mRNA expression in a time- and dose-dependent manner .", "annotated_text": "RESULTS : Glucose induced <rna>MCP-1 mRNA</rna> expression in a time- and dose-dependent manner ."}
{"id": "1529", "text": "MCP-1 protein in cell culture supernant was also increased .", "annotated_text": "<protein>MCP-1 protein</protein> in cell culture supernant was also increased ."}
{"id": "1530", "text": "Equivalent concentrations of mannitol had no significant effect .", "annotated_text": "Equivalent concentrations of mannitol had no significant effect ."}
{"id": "1531", "text": "High-glucose-conditioned supernatant possessed an increased chemotactic activity for monocytes , which was neutralized by anti-MCP-1 antibody .", "annotated_text": "High-glucose-conditioned supernatant possessed an increased chemotactic activity for <cell_type>monocytes</cell_type> , which was neutralized by <protein>anti-MCP-1 antibody</protein> ."}
{"id": "1532", "text": "EMSA revealed that glucose increased the AP-1 binding activity in a time- and dose-dependent manner , but not NF-kappaB .", "annotated_text": "EMSA revealed that glucose increased the <protein>AP-1</protein> binding activity in a time- and dose-dependent manner , but not <protein>NF-kappaB</protein> ."}
{"id": "1533", "text": "Curcumin , an inhibitor of AP-1 , dose-dependently suppressed the induction of MCP-1 mRNA by high glucose .", "annotated_text": "Curcumin , an inhibitor of <protein>AP-1</protein> , dose-dependently suppressed the induction of <rna>MCP-1 mRNA</rna> by high glucose ."}
{"id": "1534", "text": "Tyrosine kinase inhibitors such as genistein ( 12.5 to 50 micromol/L ) and herbimycin A ( 0.1 to 1 micromol/L ) inhibited the high-glucose-induced MCP-1 mRNA expression in a dose-dependent manner , and also suppressed the high-glucose-induced AP-1 binding activity .", "annotated_text": "Tyrosine kinase inhibitors such as genistein ( 12.5 to 50 micromol/L ) and herbimycin A ( 0.1 to 1 micromol/L ) inhibited the high-glucose-induced <rna>MCP-1 mRNA</rna> expression in a dose-dependent manner , and also suppressed the high-glucose-induced <protein>AP-1</protein> binding activity ."}
{"id": "1535", "text": "CONCLUSIONS : : High glucose induced mesothelial MCP-1 expression partly via the tyrosine kinase- AP-1 pathway .", "annotated_text": "CONCLUSIONS : : High glucose induced mesothelial <protein>MCP-1</protein> expression partly via the tyrosine kinase- <protein>AP-1</protein> pathway ."}
{"id": "1536", "text": "Signal thresholds and modular synergy during expression of costimulatory molecules in B lymphocytes .", "annotated_text": "Signal thresholds and modular synergy during expression of costimulatory molecules in <cell_type>B lymphocytes</cell_type> ."}
{"id": "1537", "text": "We analyzed intracellular pathways modulating surface densities of CD80 and CD86 in B cells activated through ligation of the Ag receptor , and the adhesion molecule CD54 .", "annotated_text": "We analyzed intracellular pathways modulating surface densities of <protein>CD80</protein> and <protein>CD86</protein> in <cell_type>B cells</cell_type> activated through ligation of the <protein>Ag receptor</protein> , and the <protein>adhesion molecule</protein> <protein>CD54</protein> ."}
{"id": "1538", "text": "Whereas B cell Ag receptor ( BCR ) cross-linking alone stimulated increased expression of CD86 , up-regulation of CD80 required dual stimulation with anti-IgM and anti-CD54 .", "annotated_text": "Whereas <protein>B cell Ag receptor</protein> ( <protein>BCR</protein> ) cross-linking alone stimulated increased expression of <protein>CD86</protein> , up-regulation of <protein>CD80</protein> required dual stimulation with <protein>anti-IgM</protein> and <protein>anti-CD54</protein> ."}
{"id": "1539", "text": "The principal downstream component contributed by BCR signaling , toward both CD80 and CD86 induction , was the elevated concentration of free cytoplasmic Ca ( 2+ ) , recruited by way of capacitative influx .", "annotated_text": "The principal downstream component contributed by <protein>BCR</protein> signaling , toward both <protein>CD80</protein> and <protein>CD86</protein> induction , was the elevated concentration of free cytoplasmic Ca ( 2+ ) , recruited by way of capacitative influx ."}
{"id": "1540", "text": "This alone was sufficient to generate an increase in CD86 levels .", "annotated_text": "This alone was sufficient to generate an increase in <protein>CD86</protein> levels ."}
{"id": "1541", "text": "However , CD80 enhancement required the concerted action of both intracellular Ca ( 2+ ) concentration and CD54-initiated pathways .", "annotated_text": "However , <protein>CD80</protein> enhancement required the concerted action of both intracellular Ca ( 2+ ) concentration and CD54-initiated pathways ."}
{"id": "1542", "text": "The nexus between anti-IgM and anti-CD54 stimulation , in the context of CD80 regulation , was identified to involve a self-propagating process of sequential synergy .", "annotated_text": "The nexus between anti-IgM and anti-CD54 stimulation , in the context of <protein>CD80</protein> regulation , was identified to involve a self-propagating process of sequential synergy ."}
{"id": "1543", "text": "The first step involved amplified accumulation of intracellular cAMP , as a result of cross-talk between BCR -mobilized Ca ( 2+ ) and CD54-derived signals .", "annotated_text": "The first step involved amplified accumulation of intracellular cAMP , as a result of cross-talk between <protein>BCR</protein> -mobilized Ca ( 2+ ) and CD54-derived signals ."}
{"id": "1544", "text": "This then facilitated a second synergistic interaction between Ca ( 2+ ) and cAMP , culminating in CD80 expression .", "annotated_text": "This then facilitated a second synergistic interaction between Ca ( 2+ ) and cAMP , culminating in <protein>CD80</protein> expression ."}
{"id": "1545", "text": "Our findings of distinct signal transducer requirements , with the added consequences of cross-talk , offers an explanation for variable modulation of costimulatory molecule expression in response to diverse physiological stimuli .", "annotated_text": "Our findings of distinct signal transducer requirements , with the added consequences of cross-talk , offers an explanation for variable modulation of costimulatory molecule expression in response to diverse physiological stimuli ."}
{"id": "1546", "text": "Importantly , these results also reveal how concentration threshold barriers for recruitment of individual second messengers can be overcome by constructive convergence of signaling modules .", "annotated_text": "Importantly , these results also reveal how concentration threshold barriers for recruitment of individual second messengers can be overcome by constructive convergence of signaling modules ."}
{"id": "1547", "text": "The role of Epstein-Barr virus in neoplastic transformation .", "annotated_text": "The role of Epstein-Barr virus in neoplastic transformation ."}
{"id": "1548", "text": "In this review , we focus on new data from basic , translational and clinical research relating to the Epstein-Barr virus ( EBV ) .", "annotated_text": "In this review , we focus on new data from basic , translational and clinical research relating to the Epstein-Barr virus ( EBV ) ."}
{"id": "1549", "text": "Beside its well-known tropism for B lymphocytes and epithelial cells , EBV also infects T lymphocytes , monocytes and granulocytes .", "annotated_text": "Beside its well-known tropism for <cell_type>B lymphocytes</cell_type> and <cell_type>epithelial cells</cell_type> , EBV also infects <cell_type>T lymphocytes</cell_type> , <cell_type>monocytes</cell_type> and <cell_type>granulocytes</cell_type> ."}
{"id": "1550", "text": "After primary infection , EBV persists throughout the life span in resting memory B cells , from where it is reactivated upon breakdown of cellular immunity .", "annotated_text": "After primary infection , EBV persists throughout the life span in <cell_type>resting memory B cells</cell_type> , from where it is reactivated upon breakdown of cellular immunity ."}
{"id": "1551", "text": "In the process of neoplastic transformation , the EBV-encoded latent membrane protein 1 ( LMP1 ) oncogene represents the major driving force .", "annotated_text": "In the process of neoplastic transformation , the <dna>EBV-encoded latent membrane protein 1 ( LMP1 ) oncogene</dna> represents the major driving force ."}
{"id": "1552", "text": "LMP1 acts like a constitutively activated receptor of the tumor necrosis factor receptor family and allows the amplification or bypassing of physiological regulatory signals through direct and indirect interactions with proteins of the tumor necrosis factor receptor-associated factor ( TRAF ) family .", "annotated_text": "<protein>LMP1</protein> acts like a <protein>constitutively activated receptor</protein> of the <protein>tumor necrosis factor receptor family</protein> and allows the amplification or bypassing of physiological regulatory signals through direct and indirect interactions with proteins of the <protein>tumor necrosis factor receptor-associated factor ( TRAF ) family</protein> ."}
{"id": "1553", "text": "TRAF2 -mediated NF-kappaB activation , AP-1 induction and JAK3 / STAT activation may result in sustained proliferation leading to lymphoma .", "annotated_text": "<protein>TRAF2</protein> -mediated <protein>NF-kappaB</protein> activation , <protein>AP-1</protein> induction and <protein>JAK3</protein> / <protein>STAT</protein> activation may result in sustained proliferation leading to <cell_line>lymphoma</cell_line> ."}
{"id": "1554", "text": "The ability of LMP1 to suppress germinal center formation and its capacity to mediate its own transcriptional activation shed new light on the pathogenesis of EBV-associated latency type II lymphoproliferations like Hodgkin 's disease and angioimmunoblastic lymphadenopathy .", "annotated_text": "The ability of <protein>LMP1</protein> to suppress germinal center formation and its capacity to mediate its own transcriptional activation shed new light on the pathogenesis of EBV-associated latency type II lymphoproliferations like Hodgkin 's disease and angioimmunoblastic lymphadenopathy ."}
{"id": "1555", "text": "The carboxy terminus of LMP1 is also a reliable marker for individual EBV strain identification and thus offers new possibilities in tracing the molecular events leading to posttransplant lymphoproliferative disorders ( PTLDs ) .", "annotated_text": "The <protein>carboxy terminus</protein> of <protein>LMP1</protein> is also a reliable marker for individual EBV strain identification and thus offers new possibilities in tracing the molecular events leading to posttransplant lymphoproliferative disorders ( PTLDs ) ."}
{"id": "1556", "text": "Cytotoxic T lymphocytes directed against well-characterized epitopes of EBV latency genes represent an already successful and promising therapeutic approach to EBV-associated lymphomas , in particular PTLDs", "annotated_text": "<cell_type>Cytotoxic T lymphocytes</cell_type> directed against well-characterized epitopes of <dna>EBV latency genes</dna> represent an already successful and promising therapeutic approach to <cell_line>EBV-associated lymphomas</cell_line> , in particular PTLDs"}
{"id": "1557", "text": "Interferon-alpha drives T cell-mediated immunopathology in the intestine .", "annotated_text": "<protein>Interferon-alpha</protein> drives T cell-mediated immunopathology in the intestine ."}
{"id": "1558", "text": "The ability of interferon ( IFN ) -alpha to induce autoimmunity and exacerbate Th1 diseases is well known .", "annotated_text": "The ability of <protein>interferon ( IFN ) -alpha</protein> to induce autoimmunity and exacerbate Th1 diseases is well known ."}
{"id": "1559", "text": "We have recently described enhanced expression of IFN-alpha in the mucosa of patients with celiac disease ( CD ) , a gluten-sensitive Th1-mediated enteropathy , characterized by villous atrophy and crypt cell hyperplasia .", "annotated_text": "We have recently described enhanced expression of <protein>IFN-alpha</protein> in the mucosa of patients with celiac disease ( CD ) , a gluten-sensitive Th1-mediated enteropathy , characterized by villous atrophy and crypt cell hyperplasia ."}
{"id": "1560", "text": "Previous studies from this laboratory have shown that T cell activation in explant cultures of human fetal gut can also result in villous atrophy and crypt cell hyperplasia .", "annotated_text": "Previous studies from this laboratory have shown that <cell_type>T cell</cell_type> activation in explant cultures of human fetal gut can also result in villous atrophy and crypt cell hyperplasia ."}
{"id": "1561", "text": "We have , therefore , examined changes that take place in explant cultures of human fetal gut after activation of T cells with anti-CD3 and/or IFN-alpha .", "annotated_text": "We have , therefore , examined changes that take place in explant cultures of human fetal gut after activation of <cell_type>T cells</cell_type> with <protein>anti-CD3</protein> and/or <protein>IFN-alpha</protein> ."}
{"id": "1562", "text": "We show that activation of T cells with anti-CD3 alone elicits a small IFN-gamma and TNF-alpha response with no tissue injury .", "annotated_text": "We show that activation of <cell_type>T cells</cell_type> with <protein>anti-CD3</protein> alone elicits a small <protein>IFN-gamma</protein> and <protein>TNF-alpha</protein> response with no tissue injury ."}
{"id": "1563", "text": "Similarly , no changes are seen in explants cultured with IFN-alpha alone .", "annotated_text": "Similarly , no changes are seen in explants cultured with <protein>IFN-alpha</protein> alone ."}
{"id": "1564", "text": "However , addition of IFN-alpha with anti-CD3 results in enhanced Th1 response and crypt cell hyperplasia .", "annotated_text": "However , addition of <protein>IFN-alpha</protein> with <protein>anti-CD3</protein> results in enhanced Th1 response and crypt cell hyperplasia ."}
{"id": "1565", "text": "This is associated with enhanced phosphorylation of STAT1 , STAT3 , and Fyn , a Src homology tyrosine kinase , which interacts with both TCR and IFN-alpha signal components .", "annotated_text": "This is associated with enhanced phosphorylation of <protein>STAT1</protein> , <protein>STAT3</protein> , and <protein>Fyn , a Src homology tyrosine kinase</protein> , which interacts with both TCR and IFN-alpha signal components ."}
{"id": "1566", "text": "Together these data indicate that IFN-alpha can facilitate activation of Th1-reactive cells in the gut and drive immunopathology .", "annotated_text": "Together these data indicate that <protein>IFN-alpha</protein> can facilitate activation of <cell_type>Th1-reactive cells</cell_type> in the gut and drive immunopathology ."}
{"id": "1567", "text": "Suppression of tumor necrosis factor alpha production by cAMP in human monocytes : dissociation with mRNA level and independent of interleukin-10 .", "annotated_text": "Suppression of <protein>tumor necrosis factor alpha</protein> production by cAMP in <cell_type>human monocytes</cell_type> : dissociation with mRNA level and independent of <protein>interleukin-10</protein> ."}
{"id": "1568", "text": "BACKGROUND : Elevation of cellular cAMP inhibits lipopolysaccharide ( LPS ) -stimulated tumor necrosis factor alpha ( TNF-alpha ) production and increases the expression of interleukin ( IL ) -10 in mononuclear cells .", "annotated_text": "BACKGROUND : Elevation of cellular cAMP inhibits lipopolysaccharide ( LPS ) -stimulated <protein>tumor necrosis factor alpha</protein> ( <protein>TNF-alpha</protein> ) production and increases the expression of <protein>interleukin ( IL ) -10</protein> in <cell_type>mononuclear cells</cell_type> ."}
{"id": "1569", "text": "TNF-alpha gene expression obligates activation of the transcription factor nuclear factor kappaB ( NF-kappaB ) .", "annotated_text": "<dna>TNF-alpha gene</dna> expression obligates activation of the <protein>transcription factor</protein> <protein>nuclear factor kappaB</protein> ( <protein>NF-kappaB</protein> ) ."}
{"id": "1570", "text": "Exogenous IL-10 inhibits NF-kappaB in monocytes and thus attenuates TNF-alpha production .", "annotated_text": "Exogenous <protein>IL-10</protein> inhibits <protein>NF-kappaB</protein> in <cell_type>monocytes</cell_type> and thus attenuates <protein>TNF-alpha</protein> production ."}
{"id": "1571", "text": "We examined the role of endogenous IL-10 in the regulation of NF-kappaB activation and TNF-alpha production in human monocytes by cAMP .", "annotated_text": "We examined the role of endogenous <protein>IL-10</protein> in the regulation of <protein>NF-kappaB</protein> activation and <protein>TNF-alpha</protein> production in <cell_type>human monocytes</cell_type> by cAMP ."}
{"id": "1572", "text": "METHODS : Human monocytes were stimulated with Escherichia coli LPS ( 100 ng/ml ) with and without forskolin ( FSK , 50 microM ) or dibutyryl cyclic AMP ( dbcAMP , 100 microM ) .", "annotated_text": "METHODS : <cell_type>Human monocytes</cell_type> were stimulated with Escherichia coli LPS ( 100 ng/ml ) with and without forskolin ( FSK , 50 microM ) or dibutyryl cyclic AMP ( dbcAMP , 100 microM ) ."}
{"id": "1573", "text": "Cytokine ( TNF-alpha and IL-10 ) release was measured by immunoassay .", "annotated_text": "<protein>Cytokine</protein> ( <protein>TNF-alpha</protein> and <protein>IL-10</protein> ) release was measured by immunoassay ."}
{"id": "1574", "text": "TNF-alpha mRNA was measured by reverse transcription polymerase chain reaction , and NF-kappaB DNA binding activity was assessed by gel mobility shift assay .", "annotated_text": "<rna>TNF-alpha mRNA</rna> was measured by reverse transcription polymerase chain reaction , and <protein>NF-kappaB</protein> DNA binding activity was assessed by gel mobility shift assay ."}
{"id": "1575", "text": "RESULTS : cAMP-elevating agents inhibited LPS-stimulated TNF-alpha release ( 0.77 +/- 0.13 ng/10 ( 6 ) cells in LPS + dbcAMP and 0.68 +/- 0.19 ng/10 ( 6 ) cells in LPS + FSK , both P < 0.05 vs 1.61 +/- 0.34 ng/10 ( 6 ) cells in LPS alone ) .", "annotated_text": "RESULTS : cAMP-elevating agents inhibited LPS-stimulated <protein>TNF-alpha</protein> release ( 0.77 +/- 0.13 ng/10 ( 6 ) cells in LPS + dbcAMP and 0.68 +/- 0.19 ng/10 ( 6 ) cells in LPS + FSK , both P < 0.05 vs 1.61 +/- 0.34 ng/10 ( 6 ) cells in LPS alone ) ."}
{"id": "1576", "text": "Conversely , cAMP enhanced LPS-stimulated IL-10 release ( 100 +/- 21.5 pg/10 ( 6 ) cells in LPS + dbcAMP and 110 +/- 25.2 pg/10 ( 6 ) cells in LPS + FSK , both P < 0.05 vs 53.3 +/- 12.8 pg/10 ( 6 ) cells in LPS alone ) .", "annotated_text": "Conversely , cAMP enhanced LPS-stimulated <protein>IL-10</protein> release ( 100 +/- 21.5 pg/10 ( 6 ) cells in LPS + dbcAMP and 110 +/- 25.2 pg/10 ( 6 ) cells in LPS + FSK , both P < 0.05 vs 53.3 +/- 12.8 pg/10 ( 6 ) cells in LPS alone ) ."}
{"id": "1577", "text": "Neither TNF-alpha mRNA expression nor NF-kappaB activation stimulated by LPS was inhibited by the cAMP-elevating agents .", "annotated_text": "Neither <rna>TNF-alpha mRNA</rna> expression nor <protein>NF-kappaB</protein> activation stimulated by LPS was inhibited by the cAMP-elevating agents ."}
{"id": "1578", "text": "Neutralization of IL-10 with a specific antibody did not attenuate the effect of cAMP-elevating agents on TNF-alpha production .", "annotated_text": "Neutralization of <protein>IL-10</protein> with a specific <protein>antibody</protein> did not attenuate the effect of cAMP-elevating agents on <protein>TNF-alpha</protein> production ."}
{"id": "1579", "text": "CONCLUSION : The results indicate that cAMP inhibits LPS-stimulated TNF-alpha production through a posttranscriptional mechanism that is independent of endogenous IL-10 .", "annotated_text": "CONCLUSION : The results indicate that cAMP inhibits LPS-stimulated <protein>TNF-alpha</protein> production through a posttranscriptional mechanism that is independent of endogenous <protein>IL-10</protein> ."}
{"id": "1580", "text": "Copyright 2001 Academic Press .", "annotated_text": "Copyright 2001 Academic Press ."}
{"id": "1581", "text": "Activation of the p21 ( CIP1/WAF1 ) promoter by bone morphogenetic protein-2 in mouse B lineage cells .", "annotated_text": "Activation of the <dna>p21 ( CIP1/WAF1 ) promoter</dna> by <protein>bone morphogenetic protein-2</protein> in mouse <cell_line>B lineage cells</cell_line> ."}
{"id": "1582", "text": "BMPs exert a negative growth effect on various types of cells .", "annotated_text": "<protein>BMPs</protein> exert a negative growth effect on various types of cells ."}
{"id": "1583", "text": "We have previously reported that BMP-2 inhibited the growth of HS-72 mouse hybridoma cells by inducing p21 ( CIP1/WAF1 ) expression .", "annotated_text": "We have previously reported that <protein>BMP-2</protein> inhibited the growth of <cell_line>HS-72 mouse hybridoma cells</cell_line> by inducing p21 ( CIP1/WAF1 ) expression ."}
{"id": "1584", "text": "In the present study , we demonstrated that BMP-2 activated the mouse p21 ( CIP1/WAF1 ) promoter in HS-72 cells , and that a 29-base pair ( b ) region of the promoter ( -1928/-1900 relative to the TATA box ) , conserved between mice and humans , was responsive to BMP-2 as well as expression of Smad1 , Smad4 , and constitutively active mutants of BMP type I receptors .", "annotated_text": "In the present study , we demonstrated that <protein>BMP-2</protein> activated the mouse <dna>p21 ( CIP1/WAF1 ) promoter</dna> in <cell_line>HS-72 cells</cell_line> , and that a <dna>29-base pair ( b ) region</dna> of the promoter ( -1928/-1900 relative to the <dna>TATA box</dna> ) , conserved between mice and humans , was responsive to <protein>BMP-2</protein> as well as expression of <protein>Smad1</protein> , <protein>Smad4</protein> , and constitutively active mutants of <protein>BMP type I receptors</protein> ."}
{"id": "1585", "text": "Furthermore , an oligonucleotide containing the 29-b region was found to be associated with Smad4 and phosphorylated Smad1 in the nuclear extract of BMP-2 -stimulated HS-72 cells .", "annotated_text": "Furthermore , an oligonucleotide containing the <dna>29-b region</dna> was found to be associated with <protein>Smad4</protein> and <protein>phosphorylated Smad1</protein> in the nuclear extract of <protein>BMP-2</protein> -stimulated <cell_line>HS-72 cells</cell_line> ."}
{"id": "1586", "text": "These results suggested that BMP-2 might activate p21 ( CIP1/WAF1 ) transcription by inducing a binding of Smad4 and Smad1 to the 29-b region in HS-72 cells .", "annotated_text": "These results suggested that <protein>BMP-2</protein> might activate p21 ( CIP1/WAF1 ) transcription by inducing a binding of <protein>Smad4</protein> and <protein>Smad1</protein> to the <dna>29-b region</dna> in <cell_line>HS-72 cells</cell_line> ."}
{"id": "1587", "text": "Dendritic cell development from common myeloid progenitors .", "annotated_text": "<cell_type>Dendritic cell</cell_type> development from common <cell_type>myeloid progenitors</cell_type> ."}
{"id": "1588", "text": "Dendritic cells ( DCs ) are professional antigen-presenting cells which both initiate adaptive immune responses and control tolerance to self-antigens .", "annotated_text": "<cell_type>Dendritic cells</cell_type> ( <cell_type>DCs</cell_type> ) are professional <cell_type>antigen-presenting cells</cell_type> which both initiate adaptive immune responses and control tolerance to <protein>self-antigens</protein> ."}
{"id": "1589", "text": "It has been suggested that these different effects on responder cells depend on subsets of DCs arising from either myeloid or lymphoid hematopoietic origins .", "annotated_text": "It has been suggested that these different effects on responder cells depend on subsets of <cell_type>DCs</cell_type> arising from either myeloid or lymphoid hematopoietic origins ."}
{"id": "1590", "text": "In this model , CD8 alpha+ Mac-1- DCs are supposed to be of lymphoid while CD8 alpha- Mac-1+ DCs are supposed to be of myeloid origin .", "annotated_text": "In this model , <cell_type>CD8 alpha+ Mac-1- DCs</cell_type> are supposed to be of lymphoid while <cell_type>CD8 alpha- Mac-1+ DCs</cell_type> are supposed to be of myeloid origin ."}
{"id": "1591", "text": "Here we summarize our findings that both CD8 alpha+ and CD8 alpha- DCs can arise from clonogenic common myeloid progenitors ( CMPs ) in both thymus and spleen .", "annotated_text": "Here we summarize our findings that both <cell_type>CD8 alpha+ and CD8 alpha- DCs</cell_type> can arise from <cell_type>clonogenic common myeloid progenitors</cell_type> ( <cell_type>CMPs</cell_type> ) in both thymus and spleen ."}
{"id": "1592", "text": "Therefore CD8 alpha expression DCs does not indicate a lymphoid origin and differences among CD8 alpha+ and CD8 alpha- DCs might rather reflect maturation status than ontogeny .", "annotated_text": "Therefore <protein>CD8 alpha</protein> expression <cell_type>DCs</cell_type> does not indicate a lymphoid origin and differences among <cell_type>CD8 alpha+ and CD8 alpha- DCs</cell_type> might rather reflect maturation status than ontogeny ."}
{"id": "1593", "text": "On the basis of transplantation studies , it seems likely that most of the DCs in secondary lymphoid organs and a substantial fraction of thymic DCs are myeloid-derived .", "annotated_text": "On the basis of transplantation studies , it seems likely that most of the <cell_type>DCs</cell_type> in secondary lymphoid organs and a substantial fraction of <cell_type>thymic DCs</cell_type> are myeloid-derived ."}
{"id": "1594", "text": "Macrophage stimulation with Murabutide , an HIV-suppressive muramyl peptide derivative , selectively activates extracellular signal-regulated kinases 1 and 2 , C/EBPbeta and STAT1 : role of CD14 and Toll-like receptors 2 and 4 .", "annotated_text": "Macrophage stimulation with Murabutide , an HIV-suppressive muramyl peptide derivative , selectively activates <protein>extracellular signal-regulated kinases 1 and 2</protein> , <protein>C/EBPbeta</protein> and <protein>STAT1</protein> : role of <protein>CD14</protein> and <protein>Toll-like receptors 2 and 4</protein> ."}
{"id": "1595", "text": "The smallest unit of bacterial peptidoglycans known to be endowed with biological activities is muramyl dipeptide ( MDP ) .", "annotated_text": "The smallest unit of bacterial peptidoglycans known to be endowed with biological activities is muramyl dipeptide ( MDP ) ."}
{"id": "1596", "text": "A clinically acceptable synthetic derivative of MDP , namely murabutide ( MB ) , has been found to present interesting pharmacological properties and to suppress HIV-1 replication in monocyte-derived macrophages ( MDM ) .", "annotated_text": "A clinically acceptable synthetic derivative of MDP , namely murabutide ( MB ) , has been found to present interesting pharmacological properties and to suppress HIV-1 replication in <cell_type>monocyte-derived macrophages</cell_type> ( <cell_type>MDM</cell_type> ) ."}
{"id": "1597", "text": "We have addressed the signaling events activated in MDM following stimulation with either MB or the potent immunostimulant LPS .", "annotated_text": "We have addressed the signaling events activated in <cell_type>MDM</cell_type> following stimulation with either MB or the potent immunostimulant LPS ."}
{"id": "1598", "text": "We also examined whether signaling by muramyl peptides involves the use of cell surface receptors , including CD14 and Toll-like receptor 2 ( TLR2 ) or TLR4 that are known to be signal-transducing receptors for other bacterial cell wall components .", "annotated_text": "We also examined whether signaling by muramyl peptides involves the use of <protein>cell surface receptors</protein> , including <protein>CD14</protein> and <protein>Toll-like receptor 2</protein> ( <protein>TLR2</protein> ) or <protein>TLR4</protein> that are known to be <protein>signal-transducing receptors</protein> for other bacterial cell wall components ."}
{"id": "1599", "text": "We demonstrate that , unlike LPS , the safe immunomodulator MB selectively activates extracellular signal-regulated kinases ( Erk ) 1/2 , in the absence of detectable Jun N-terminal kinase ( JNK ) or p38 mitogen-activated kinase activation .", "annotated_text": "We demonstrate that , unlike LPS , the safe immunomodulator MB selectively activates <protein>extracellular signal-regulated kinases ( Erk ) 1/2</protein> , in the absence of detectable <protein>Jun N-terminal kinase</protein> ( <protein>JNK</protein> ) or <protein>p38 mitogen-activated kinase</protein> activation ."}
{"id": "1600", "text": "Furthermore , STAT1 activation but weak or no activation of STAT3 or STAT5 respectively , could be detected in MB-stimulated MDM .", "annotated_text": "Furthermore , <protein>STAT1</protein> activation but weak or no activation of <protein>STAT3</protein> or <protein>STAT5</protein> respectively , could be detected in <cell_type>MB-stimulated MDM</cell_type> ."}
{"id": "1601", "text": "Using MonoMac6 cells , we observed high C/EBPbeta and AP-1 but weaker and transient NF-kappaB activation by MB .", "annotated_text": "Using <cell_line>MonoMac6 cells</cell_line> , we observed high <protein>C/EBPbeta</protein> and <protein>AP-1</protein> but weaker and transient <protein>NF-kappaB</protein> activation by MB ."}
{"id": "1602", "text": "Moreover , the truncated form of C/EBPbeta , known to repress HIV-1 transcription , was detected in extracts from MB-treated THP-1 cells .", "annotated_text": "Moreover , the truncated form of <protein>C/EBPbeta</protein> , known to repress HIV-1 transcription , was detected in extracts from <cell_line>MB-treated THP-1 cells</cell_line> ."}
{"id": "1603", "text": "Surprisingly , neither MB nor MDP were able to transduce signals via CD14 and TLR2 or 4 .", "annotated_text": "Surprisingly , neither MB nor MDP were able to transduce signals via <protein>CD14</protein> and <protein>TLR2 or 4</protein> ."}
{"id": "1604", "text": "These findings present major differences in the early cell activation process between LPS and muramyl peptides , and strongly argue for the implication of co-receptors other than TLR2 and TLR4 in mediating the signaling events induced by defined subunits of bacterial peptidoglycans .", "annotated_text": "These findings present major differences in the early cell activation process between LPS and muramyl peptides , and strongly argue for the implication of <protein>co-receptors</protein> other than <protein>TLR2</protein> and <protein>TLR4</protein> in mediating the signaling events induced by defined subunits of bacterial peptidoglycans ."}
{"id": "1605", "text": "Nuclear peroxisome proliferator-activated receptors alpha and gamma have opposing effects on monocyte chemotaxis in endometriosis .", "annotated_text": "<protein>Nuclear peroxisome proliferator-activated receptors alpha and gamma</protein> have opposing effects on monocyte chemotaxis in endometriosis ."}
{"id": "1606", "text": "The peroxisome proliferator-activated receptors ( PPARs ) alpha and gamma are nuclear receptors that play important roles in inflammatory diseases like ulcerative colitis and arthritis .", "annotated_text": "The <protein>peroxisome proliferator-activated receptors ( PPARs ) alpha and gamma</protein> are <protein>nuclear receptors</protein> that play important roles in inflammatory diseases like ulcerative colitis and arthritis ."}
{"id": "1607", "text": "In this study , we examined the possible role of PPARs in macrophage attraction into the peritoneal cavity of patients with endometriosis .", "annotated_text": "In this study , we examined the possible role of <protein>PPARs</protein> in macrophage attraction into the peritoneal cavity of patients with endometriosis ."}
{"id": "1608", "text": "We identified PPAR-alpha and -gamma messenger RNA by RT-PCR and protein by immunoblotting of lysates of peritoneal macrophages and monocytic U937 cells .", "annotated_text": "We identified <rna>PPAR-alpha and -gamma</rna> messenger RNA by RT-PCR and protein by immunoblotting of lysates of <cell_type>peritoneal macrophages</cell_type> and <cell_line>monocytic U937 cells</cell_line> ."}
{"id": "1609", "text": "Using immunocytochemistry , we localized PPAR-alpha and -gamma within the nuclei of both cell types .", "annotated_text": "Using immunocytochemistry , we localized <protein>PPAR-alpha and -gamma</protein> within the nuclei of both cell types ."}
{"id": "1610", "text": "Monocyte chemotactic activity of peritoneal fluid from patients with endometriosis was quantified in Boyden chambers .", "annotated_text": "Monocyte chemotactic activity of peritoneal fluid from patients with endometriosis was quantified in Boyden chambers ."}
{"id": "1611", "text": "Migration of U937 cells was increased by WY 14643 and reduced by rosiglitazone .", "annotated_text": "Migration of <cell_line>U937 cells</cell_line> was increased by WY 14643 and reduced by rosiglitazone ."}
{"id": "1612", "text": "Peritoneal fluid from patients with endometriosis activated U937 cells transiently transfected with a PPAR-alpha/GAL4 luciferase reporter .", "annotated_text": "Peritoneal fluid from patients with endometriosis activated <cell_line>U937 cells</cell_line> transiently transfected with a <dna>PPAR-alpha/GAL4 luciferase reporter</dna> ."}
{"id": "1613", "text": "By contrast , peritoneal fluid did not cause significant activation of PPAR-gamma/GAL4 constructs .", "annotated_text": "By contrast , peritoneal fluid did not cause significant activation of <dna>PPAR-gamma/GAL4 constructs</dna> ."}
{"id": "1614", "text": "The U937 cells transiently transfected with a PPAR response element luciferase reporter showed disease stage-dependent up-regulation when treated with peritoneal fluid from patients with endometriosis .", "annotated_text": "The <cell_line>U937 cells</cell_line> transiently transfected with a <dna>PPAR response element luciferase reporter</dna> showed disease stage-dependent up-regulation when treated with peritoneal fluid from patients with endometriosis ."}
{"id": "1615", "text": "Treatment with peritoneal fluid from healthy controls down-regulated PPAR response element transactivation .", "annotated_text": "Treatment with peritoneal fluid from healthy controls down-regulated PPAR response element transactivation ."}
{"id": "1616", "text": "We conclude that peritoneal fluid of endometriosis patients contains activators of PPAR-alpha that stimulate macrophage chemotaxis .", "annotated_text": "We conclude that peritoneal fluid of endometriosis patients contains activators of <protein>PPAR-alpha</protein> that stimulate macrophage chemotaxis ."}
{"id": "1617", "text": "Inhibitors of PPAR-alpha or activators of PPAR-gamma could be developed for the treatment of inflammation associated with endometriosis .", "annotated_text": "Inhibitors of <protein>PPAR-alpha</protein> or activators of <protein>PPAR-gamma</protein> could be developed for the treatment of inflammation associated with endometriosis ."}
{"id": "1618", "text": "Long-term-impaired expression of nuclear factor-kappa B and I kappa B alpha in peripheral blood mononuclear cells of trauma patients .", "annotated_text": "Long-term-impaired expression of <protein>nuclear factor-kappa B</protein> and <protein>I kappa B alpha</protein> in <cell_type>peripheral blood mononuclear cells</cell_type> of trauma patients ."}
{"id": "1619", "text": "Nuclear factor ( NF ) -kappa B expression and dimer characteristics were studied in peripheral blood mononuclear cells ( PBMCs ) of major-trauma patients and healthy controls .", "annotated_text": "<protein>Nuclear factor ( NF ) -kappa B</protein> expression and dimer characteristics were studied in <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMCs</cell_type> ) of major-trauma patients and healthy controls ."}
{"id": "1620", "text": "Analysis of PBMCs on days 1 , 3 , 5 , and 10 after trauma revealed that expression of both p65p50 heterodimers and p50p50 homodimers was significantly reduced compared with that in controls .", "annotated_text": "Analysis of <cell_type>PBMCs</cell_type> on days 1 , 3 , 5 , and 10 after trauma revealed that expression of both <protein>p65p50 heterodimers</protein> and <protein>p50p50 homodimers</protein> was significantly reduced compared with that in controls ."}
{"id": "1621", "text": "In vitro lipopolysaccharide ( LPS ) stimulation of PBMCs induced NF-kappa B translocation .", "annotated_text": "In vitro lipopolysaccharide ( LPS ) stimulation of <cell_type>PBMCs</cell_type> induced NF-kappa B translocation ."}
{"id": "1622", "text": "However , throughout the survey , p65p50 activation remained significantly lower in trauma patients than in controls .", "annotated_text": "However , throughout the survey , p65p50 activation remained significantly lower in trauma patients than in controls ."}
{"id": "1623", "text": "After LPS stimulation in vitro , the p65p50/p50p50 ratio was significantly lower in PBMCs from trauma patients than from healthy controls .", "annotated_text": "After LPS stimulation in vitro , the p65p50/p50p50 ratio was significantly lower in <cell_type>PBMCs</cell_type> from trauma patients than from healthy controls ."}
{"id": "1624", "text": "The ex vivo expression of I kappa B alpha was higher in PBMCs of controls than of trauma patients .", "annotated_text": "The ex vivo expression of <protein>I kappa B alpha</protein> was higher in <cell_type>PBMCs</cell_type> of controls than of trauma patients ."}
{"id": "1625", "text": "LPS did not induce I kappa B expression in PBMCs from trauma patients , but strong induction was obtained with staphylococci , suggesting that this defect is not universal and depends on the nature of the activating signal .", "annotated_text": "LPS did not induce I kappa B expression in <cell_type>PBMCs</cell_type> from trauma patients , but strong induction was obtained with staphylococci , suggesting that this defect is not universal and depends on the nature of the activating signal ."}
{"id": "1626", "text": "Although no direct correlation was found between levels of interleukin-10 or transforming growth factor-beta and NF-kappa B , these immunosuppressive cytokines were significantly elevated in trauma patients by 10 days after admission .", "annotated_text": "Although no direct correlation was found between levels of <protein>interleukin-10</protein> or <protein>transforming growth factor-beta</protein> and <protein>NF-kappa B</protein> , these <protein>immunosuppressive cytokines</protein> were significantly elevated in trauma patients by 10 days after admission ."}
{"id": "1627", "text": "The long-term low-basal and LPS-induced nuclear translocation of NF-kappa B recalled long-term immunoparalysis observed in patients with severe inflammatory stress such as trauma .", "annotated_text": "The long-term low-basal and LPS-induced nuclear translocation of <protein>NF-kappa B</protein> recalled long-term immunoparalysis observed in patients with severe inflammatory stress such as trauma ."}
{"id": "1628", "text": "Hepatic ischemia-reperfusion injury .", "annotated_text": "Hepatic ischemia-reperfusion injury ."}
{"id": "1629", "text": "BACKGROUND : The morbidity associated with liver transplantation and major hepatic resections is partly a result of ischemia-reperfusion injury .", "annotated_text": "BACKGROUND : The morbidity associated with liver transplantation and major hepatic resections is partly a result of ischemia-reperfusion injury ."}
{"id": "1630", "text": "DATA SOURCES : The entire world literature on the subject was searched via Medline .", "annotated_text": "DATA SOURCES : The entire world literature on the subject was searched via Medline ."}
{"id": "1631", "text": "Keywords included reperfusion injury , transplantation , liver resection , nitric oxide , endothelin , cytokines , Kupffer cells , ischemic/ischaemic preconditioning , and nuclear factor-kappa B .", "annotated_text": "Keywords included reperfusion injury , transplantation , liver resection , nitric oxide , endothelin , <protein>cytokines</protein> , <cell_type>Kupffer cells</cell_type> , ischemic/ischaemic preconditioning , and <protein>nuclear factor-kappa B</protein> ."}
{"id": "1632", "text": "CONCLUSIONS : An imbalance between endothelin and nitric oxide levels results in failure of the hepatic microcirculation at the onset of reperfusion .", "annotated_text": "CONCLUSIONS : An imbalance between endothelin and nitric oxide levels results in failure of the hepatic microcirculation at the onset of reperfusion ."}
{"id": "1633", "text": "Activation of nuclear factor-kappa B in the liver promotes proinflammatory cytokine and adhesion molecule synthesis .", "annotated_text": "Activation of <protein>nuclear factor-kappa B</protein> in the liver promotes <protein>proinflammatory cytokine</protein> and <protein>adhesion molecule</protein> synthesis ."}
{"id": "1634", "text": "These result in oxygen-derived free radical production and neutrophil recruitment , further contributing to cellular injury .", "annotated_text": "These result in oxygen-derived free radical production and neutrophil recruitment , further contributing to cellular injury ."}
{"id": "1635", "text": "Various therapeutic modalities acting on the above mediators have been successfully used to attenuate reperfusion injury in animal models of hepatic transplantation and resection .", "annotated_text": "Various therapeutic modalities acting on the above mediators have been successfully used to attenuate reperfusion injury in animal models of hepatic transplantation and resection ."}
{"id": "1636", "text": "Application of the knowledge gained from animal models of hepatic ischemia-reperfusion to the clinical setting will improve the outcome of hepatic surgery .", "annotated_text": "Application of the knowledge gained from animal models of hepatic ischemia-reperfusion to the clinical setting will improve the outcome of hepatic surgery ."}
{"id": "1637", "text": "Down-regulation of IL-12 p40 gene in Plasmodium berghei-infected mice .", "annotated_text": "Down-regulation of <dna>IL-12 p40 gene</dna> in Plasmodium berghei-infected mice ."}
{"id": "1638", "text": "We analyzed the mechanism that causes suppression of IL-12 p40 gene induction during Plasmodium berghei infection .", "annotated_text": "We analyzed the mechanism that causes suppression of <dna>IL-12 p40 gene</dna> induction during Plasmodium berghei infection ."}
{"id": "1639", "text": "Although IL-12 together with IFN-gamma plays an important role in protection against pathogenic infection , the IL-12 p70 protein production of infected macrophages is lower than that by the uninfected macrophages .", "annotated_text": "Although <protein>IL-12</protein> together with <protein>IFN-gamma</protein> plays an important role in protection against pathogenic infection , the <protein>IL-12 p70 protein</protein> production of <cell_type>infected macrophages</cell_type> is lower than that by the <cell_type>uninfected macrophages</cell_type> ."}
{"id": "1640", "text": "We showed in the present study that the induction of IL-12 p40 gene but not IL-12 p35 gene in macrophages of P. berghei-infected mice was profoundly inhibited .", "annotated_text": "We showed in the present study that the induction of <dna>IL-12 p40 gene</dna> but not <dna>IL-12 p35 gene</dna> in <cell_type>macrophages</cell_type> of P. berghei-infected mice was profoundly inhibited ."}
{"id": "1641", "text": "The inhibition was induced by interaction with macrophages that had contacted with P. berghei-infected erythrocytes and was mediated by a soluble factor , IL-10 .", "annotated_text": "The inhibition was induced by interaction with <cell_type>macrophages</cell_type> that had contacted with <cell_type>P. berghei-infected erythrocytes</cell_type> and was mediated by a soluble factor , <protein>IL-10</protein> ."}
{"id": "1642", "text": "There was comparable activation of NF-kappaB in uninfected and infected cells .", "annotated_text": "There was comparable activation of <protein>NF-kappaB</protein> in <cell_type>uninfected and infected cells</cell_type> ."}
{"id": "1643", "text": "The induction of IFN-regulatory factor-1 gene was comparable in transcription level in uninfected and infected cells , while the unidentified complex formation of IFN-regulatory factor-1 was observed in infected cells .", "annotated_text": "The induction of <dna>IFN-regulatory factor-1 gene</dna> was comparable in transcription level in <cell_type>uninfected and infected cells</cell_type> , while the unidentified complex formation of <protein>IFN-regulatory factor-1</protein> was observed in <cell_type>infected cells</cell_type> ."}
{"id": "1644", "text": "Therefore , the inhibition of the IL-12 p40 gene induction appeared to be regulated at transcriptional regulation level of the gene .", "annotated_text": "Therefore , the inhibition of the <dna>IL-12 p40 gene</dna> induction appeared to be regulated at transcriptional regulation level of the gene ."}
{"id": "1645", "text": "The Friend of GATA proteins U-shaped , FOG-1 , and FOG-2 function as negative regulators of blood , heart , and eye development in Drosophila .", "annotated_text": "The <protein>Friend of GATA proteins</protein> U-shaped , <protein>FOG-1</protein> , and <protein>FOG-2</protein> function as negative regulators of blood , heart , and eye development in Drosophila ."}
{"id": "1646", "text": "Friend of GATA ( FOG ) proteins regulate GATA factor-activated gene transcription .", "annotated_text": "<protein>Friend of GATA ( FOG ) proteins</protein> regulate GATA factor-activated gene transcription ."}
{"id": "1647", "text": "During vertebrate hematopoiesis , FOG and GATA proteins cooperate to promote erythrocyte and megakaryocyte differentiation .", "annotated_text": "During vertebrate hematopoiesis , <protein>FOG and GATA proteins</protein> cooperate to promote erythrocyte and megakaryocyte differentiation ."}
{"id": "1648", "text": "The Drosophila FOG homologue U-shaped ( Ush ) is expressed similarly in the blood cell anlage during embryogenesis .", "annotated_text": "The <protein>Drosophila FOG homologue U-shaped</protein> ( <protein>Ush</protein> ) is expressed similarly in the blood cell anlage during embryogenesis ."}
{"id": "1649", "text": "During hematopoiesis , the acute myeloid leukemia 1 homologue Lozenge and Glial cells missing are required for the production of crystal cells and plasmatocytes , respectively .", "annotated_text": "During hematopoiesis , the acute myeloid leukemia 1 homologue <cell_type>Lozenge and Glial cells</cell_type> missing are required for the production of <cell_type>crystal cells</cell_type> and <cell_type>plasmatocytes</cell_type> , respectively ."}
{"id": "1650", "text": "However , additional factors have been predicted to control crystal cell proliferation .", "annotated_text": "However , additional factors have been predicted to control crystal cell proliferation ."}
{"id": "1651", "text": "In this report , we show that Ush is expressed in hemocyte precursors and plasmatocytes throughout embryogenesis and larval development , and the GATA factor Serpent is essential for Ush embryonic expression .", "annotated_text": "In this report , we show that <protein>Ush</protein> is expressed in <cell_type>hemocyte precursors</cell_type> and <cell_type>plasmatocytes</cell_type> throughout embryogenesis and larval development , and the <protein>GATA factor Serpent</protein> is essential for <protein>Ush</protein> embryonic expression ."}
{"id": "1652", "text": "Furthermore , loss of ush function results in an overproduction of crystal cells , whereas forced expression of Ush reduces this cell population .", "annotated_text": "Furthermore , loss of ush function results in an overproduction of <cell_type>crystal cells</cell_type> , whereas forced expression of <protein>Ush</protein> reduces this cell population ."}
{"id": "1653", "text": "Murine FOG-1 and FOG-2 also can repress crystal cell production , but a mutant version of FOG-2 lacking a conserved motif that binds the corepressor C-terminal binding protein fails to affect the cell lineage .", "annotated_text": "<protein>Murine FOG-1 and FOG-2</protein> also can repress crystal cell production , but a mutant version of <protein>FOG-2</protein> lacking a conserved motif that binds the <protein>corepressor C-terminal binding protein</protein> fails to affect the cell lineage ."}
{"id": "1654", "text": "The GATA factor Pannier ( Pnr ) is required for eye and heart development in Drosophila .", "annotated_text": "The <protein>GATA factor Pannier</protein> ( <protein>Pnr</protein> ) is required for eye and heart development in Drosophila ."}
{"id": "1655", "text": "When Ush , FOG-1 , FOG-2 , or mutant FOG-2 is coexpressed with Pnr during these developmental processes , severe eye and heart phenotypes result , consistent with a conserved negative regulation of Pnr function .", "annotated_text": "When <protein>Ush</protein> , <protein>FOG-1</protein> , <protein>FOG-2</protein> , or <protein>mutant FOG-2</protein> is coexpressed with <protein>Pnr</protein> during these developmental processes , severe eye and heart phenotypes result , consistent with a conserved negative regulation of <protein>Pnr</protein> function ."}
{"id": "1656", "text": "These results indicate that the fly and mouse FOG proteins function similarly in three distinct cellular contexts in Drosophila , but may use different mechanisms to regulate genetic events in blood vs . cardial or eye cell lineages", "annotated_text": "These results indicate that the fly and mouse <protein>FOG proteins</protein> function similarly in three distinct cellular contexts in Drosophila , but may use different mechanisms to regulate genetic events in blood vs . <cell_line>cardial or eye cell lineages</cell_line>"}
{"id": "1657", "text": "The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1 .", "annotated_text": "The <protein>RING finger protein</protein> <protein>Siah-1</protein> regulates the level of the <protein>transcriptional coactivator</protein> <protein>OBF-1</protein> ."}
{"id": "1658", "text": "The transcriptional coactivator OBF-1 , which interacts with Oct-1 and Oct-2 and the octamer site DNA , has been shown to be critical for development of a normal immune response and the formation of germinal centers in secondary lymphoid organs .", "annotated_text": "The <protein>transcriptional coactivator</protein> <protein>OBF-1</protein> , which interacts with <protein>Oct-1</protein> and <protein>Oct-2</protein> and the <dna>octamer site DNA</dna> , has been shown to be critical for development of a normal immune response and the formation of germinal centers in secondary lymphoid organs ."}
{"id": "1659", "text": "Here we have identified the RING finger protein Siah-1 as a protein interacting specifically with OBF-1 .", "annotated_text": "Here we have identified the <protein>RING finger protein</protein> <protein>Siah-1</protein> as a protein interacting specifically with <protein>OBF-1</protein> ."}
{"id": "1660", "text": "This interaction is mediated by the C-terminal part of Siah-1 and by residues in the N-terminus of OBF-1 , partly distinct from the residues required for formation of a complex with the Oct POU domains and the DNA .", "annotated_text": "This interaction is mediated by the <protein>C-terminal</protein> part of <protein>Siah-1</protein> and by residues in the <protein>N-terminus</protein> of <protein>OBF-1</protein> , partly distinct from the residues required for formation of a complex with the <protein>Oct POU domains</protein> and the DNA ."}
{"id": "1661", "text": "Interaction between Siah-1 and OBF-1 leads to downregulation of OBF-1 protein level but not mRNA , and to a corresponding reduction in octamer site-dependent transcription activation .", "annotated_text": "Interaction between <protein>Siah-1</protein> and <protein>OBF-1</protein> leads to downregulation of OBF-1 protein level but not mRNA , and to a corresponding reduction in octamer site-dependent transcription activation ."}
{"id": "1662", "text": "Inhibition of the ubiquitin-proteasome pathway in B cells leads to elevated levels of OBF-1 protein .", "annotated_text": "Inhibition of the ubiquitin-proteasome pathway in <cell_type>B cells</cell_type> leads to elevated levels of <protein>OBF-1 protein</protein> ."}
{"id": "1663", "text": "Furthermore , in immunized mice , OBF-1 protein amounts are dramatically increased in primary activated B cells , without concomitant increase in OBF-1 mRNA .", "annotated_text": "Furthermore , in immunized mice , <protein>OBF-1 protein</protein> amounts are dramatically increased in <cell_type>primary activated B cells</cell_type> , without concomitant increase in <rna>OBF-1 mRNA</rna> ."}
{"id": "1664", "text": "These data suggest that Siah-1 is part of a novel regulatory loop controlling the level of OBF-1 protein in B cells .", "annotated_text": "These data suggest that <protein>Siah-1</protein> is part of a novel regulatory loop controlling the level of <protein>OBF-1 protein</protein> in <cell_type>B cells</cell_type> ."}
{"id": "1665", "text": "The beta-catenin -- TCF-1 pathway ensures CD4 ( + ) CD8 ( + ) thymocyte survival .", "annotated_text": "The beta-catenin -- TCF-1 pathway ensures <cell_type>CD4 ( + ) CD8 ( + ) thymocyte</cell_type> survival ."}
{"id": "1666", "text": "The association of trans-acting T cell factors ( TCFs ) or lymphoid enhancer factor 1 ( LEF-1 ) with their coactivator beta-catenin mediates transient transcriptional responses to extracellular Wnt signals .", "annotated_text": "The association of <protein>trans-acting T cell factors</protein> ( <protein>TCFs</protein> ) or <protein>lymphoid enhancer factor 1</protein> ( <protein>LEF-1</protein> ) with their coactivator beta-catenin mediates transient transcriptional responses to extracellular Wnt signals ."}
{"id": "1667", "text": "We show here that T cell maturation depends on the presence of the beta-catenin -- binding domain in TCF-1 .", "annotated_text": "We show here that T cell maturation depends on the presence of the <protein>beta-catenin -- binding domain</protein> in <protein>TCF-1</protein> ."}
{"id": "1668", "text": "This domain is necessary to mediate the survival of immature CD4 ( + ) CD8 ( + ) double-positive ( DP ) thymocytes .", "annotated_text": "This domain is necessary to mediate the survival of immature <cell_type>CD4 ( + ) CD8 ( + ) double-positive ( DP ) thymocytes</cell_type> ."}
{"id": "1669", "text": "Accelerated spontaneous thymocyte death in the absence of TCF-1 correlates with aberrantly low expression of the anti-apoptotic protein Bcl-x ( L ) .", "annotated_text": "Accelerated spontaneous thymocyte death in the absence of <protein>TCF-1</protein> correlates with aberrantly low expression of the <protein>anti-apoptotic protein</protein> <protein>Bcl-x ( L )</protein> ."}
{"id": "1670", "text": "Increasing anti-apoptotic effectors in thymocytes by the use of a Bcl-2 transgene rescued TCF-1-deficient DP thymocytes from apoptosis .", "annotated_text": "Increasing anti-apoptotic effectors in <cell_type>thymocytes</cell_type> by the use of a <dna>Bcl-2 transgene</dna> rescued <cell_type>TCF-1-deficient DP thymocytes</cell_type> from apoptosis ."}
{"id": "1671", "text": "Thus , TCF-1 , upon association with beta-catenin , transiently ensures the survival of immature T cells , which enables them to generate and edit T cell receptor ( TCR ) alpha chains and attempt TCR -mediated positive selection .", "annotated_text": "Thus , <protein>TCF-1</protein> , upon association with beta-catenin , transiently ensures the survival of <cell_type>immature T cells</cell_type> , which enables them to generate and edit <protein>T cell receptor ( TCR ) alpha chains</protein> and attempt <protein>TCR</protein> -mediated positive selection ."}
{"id": "1672", "text": "TRAIL/Apo2L ligand selectively induces apoptosis and overcomes drug resistance in multiple myeloma : therapeutic applications .", "annotated_text": "<protein>TRAIL/Apo2L ligand</protein> selectively induces apoptosis and overcomes drug resistance in multiple myeloma : therapeutic applications ."}
{"id": "1673", "text": "Multiple myeloma ( MM ) remains incurable and novel treatments are urgently needed .", "annotated_text": "Multiple myeloma ( MM ) remains incurable and novel treatments are urgently needed ."}
{"id": "1674", "text": "Preclinical in vitro and in vivo evaluations were performed to assess the potential therapeutic applications of human recombinant tumor necrosis factor ( TNF ) -related apoptosis-inducing ligand/Apo2 ligand ( TRAIL/Apo2L ) in MM .", "annotated_text": "Preclinical in vitro and in vivo evaluations were performed to assess the potential therapeutic applications of human recombinant <protein>tumor necrosis factor ( TNF ) -related apoptosis-inducing ligand/Apo2 ligand</protein> ( <protein>TRAIL/Apo2L</protein> ) in MM ."}
{"id": "1675", "text": "TRAIL/Apo2L potently induced apoptosis of MM cells from patients and the majority of MM cell lines , including cells sensitive or resistant to dexamethasone ( Dex ) , doxorubicin ( Dox ) , melphalan , and mitoxantrone .", "annotated_text": "<protein>TRAIL/Apo2L</protein> potently induced apoptosis of <cell_type>MM cells</cell_type> from patients and the majority of <cell_line>MM cell lines</cell_line> , including cells sensitive or resistant to dexamethasone ( Dex ) , doxorubicin ( Dox ) , melphalan , and mitoxantrone ."}
{"id": "1676", "text": "TRAIL/Apo2L also overcame the survival effect of interleukin 6 on MM cells and did not affect the survival of peripheral blood and bone marrow mononuclear cells and purified B cells from healthy donors .", "annotated_text": "<protein>TRAIL/Apo2L</protein> also overcame the survival effect of <protein>interleukin 6</protein> on <cell_type>MM cells</cell_type> and did not affect the survival of <cell_type>peripheral blood and bone marrow mononuclear cells</cell_type> and <cell_type>purified B cells</cell_type> from healthy donors ."}
{"id": "1677", "text": "The status of the TRAIL receptors ( assessed by immunoblotting and flow cytometry ) could not predict TRAIL sensitivity of MM cells .", "annotated_text": "The status of the <protein>TRAIL receptors</protein> ( assessed by immunoblotting and flow cytometry ) could not predict TRAIL sensitivity of <cell_type>MM cells</cell_type> ."}
{"id": "1678", "text": "The anti-MM activity of TRAIL/Apo2L was confirmed in nu/xid/bg mice xenografted with human MM cells ; TRAIL ( 500 microg intraperitoneally daily for 14 days ) was well tolerated and significantly suppressed the growth of plasmacytomas .", "annotated_text": "The anti-MM activity of <protein>TRAIL/Apo2L</protein> was confirmed in nu/xid/bg mice xenografted with <cell_type>human MM cells</cell_type> ; <protein>TRAIL</protein> ( 500 microg intraperitoneally daily for 14 days ) was well tolerated and significantly suppressed the growth of <cell_type>plasmacytomas</cell_type> ."}
{"id": "1679", "text": "Dox up-regulated the expression of the TRAIL receptor death receptor 5 ( DR5 ) and synergistically enhanced the effect of TRAIL not only against MM cells sensitive to , but also against those resistant to , Dex- or Dox-induced apoptosis .", "annotated_text": "Dox up-regulated the expression of the <protein>TRAIL receptor</protein> <protein>death receptor 5</protein> ( <protein>DR5</protein> ) and synergistically enhanced the effect of <protein>TRAIL</protein> not only against <cell_type>MM cells</cell_type> sensitive to , but also against those resistant to , Dex- or Dox-induced apoptosis ."}
{"id": "1680", "text": "Nuclear factor ( NF ) -kappaB inhibitors , such as SN50 ( a cell-permeable inhibitor of the nuclear translocation and transcriptional activity of NF-kappaB ) or the proteasome inhibitor PS-341 , enhanced the proapoptotic activity of TRAIL/Apo2L against TRAIL-sensitive MM cells , whereas SN50 reversed the TRAIL resistance of ARH-77 and IM-9 MM cells .", "annotated_text": "Nuclear factor ( NF ) -kappaB inhibitors , such as SN50 ( a cell-permeable inhibitor of the nuclear translocation and transcriptional activity of <protein>NF-kappaB</protein> ) or the proteasome inhibitor PS-341 , enhanced the proapoptotic activity of <protein>TRAIL/Apo2L</protein> against <cell_type>TRAIL-sensitive MM cells</cell_type> , whereas SN50 reversed the TRAIL resistance of <cell_type>ARH-77 and IM-9 MM cells</cell_type> ."}
{"id": "1681", "text": "Importantly , normal B lymphocytes were not sensitized to TRAIL by either Dox , SN50 , or PS-341 .", "annotated_text": "Importantly , <cell_type>normal B lymphocytes</cell_type> were not sensitized to <protein>TRAIL</protein> by either Dox , SN50 , or PS-341 ."}
{"id": "1682", "text": "These preclinical studies suggest that TRAIL/Apo2L can overcome conventional drug resistance and provide the basis for clinical trials of TRAIL -based treatment regimens to improve outcome in patients with MM .", "annotated_text": "These preclinical studies suggest that <protein>TRAIL/Apo2L</protein> can overcome conventional drug resistance and provide the basis for clinical trials of <protein>TRAIL</protein> -based treatment regimens to improve outcome in patients with MM ."}
{"id": "1683", "text": "( Blood. 2001 ; 98 : 795-804 )", "annotated_text": "( Blood. 2001 ; 98 : 795-804 )"}
{"id": "1684", "text": "CD28 costimulation is required not only to induce IL-12 receptor but also to render janus kinases/STAT4 responsive to IL-12 stimulation in TCR-triggered T cells .", "annotated_text": "<protein>CD28</protein> costimulation is required not only to induce <protein>IL-12 receptor</protein> but also to render <protein>janus kinases/STAT4</protein> responsive to <protein>IL-12</protein> stimulation in <cell_type>TCR-triggered T cells</cell_type> ."}
{"id": "1685", "text": "The activation of resting T cells for the acquisition of various functions depends on whether CD28 costimulatory signals are provided upon T cell receptor stimulation .", "annotated_text": "The activation of <cell_type>resting T cells</cell_type> for the acquisition of various functions depends on whether CD28 costimulatory signals are provided upon T cell receptor stimulation ."}
{"id": "1686", "text": "Here , we investigated how CD28 costimulation functions to allow TCR -triggered resting T cells to acquire IL-12 responsiveness .", "annotated_text": "Here , we investigated how CD28 costimulation functions to allow <protein>TCR</protein> -triggered <cell_type>resting T cells</cell_type> to acquire <protein>IL-12</protein> responsiveness ."}
{"id": "1687", "text": "When T cells are stimulated with low doses of anti-CD3 mAb , CD28 costimulation was required for the optimal levels of IL-12 receptor ( IL-12R ) expression .", "annotated_text": "When <cell_type>T cells</cell_type> are stimulated with low doses of <protein>anti-CD3 mAb</protein> , CD28 costimulation was required for the optimal levels of <protein>IL-12 receptor</protein> ( <protein>IL-12R</protein> ) expression ."}
{"id": "1688", "text": "However , stimulation of T cells with high doses of anti-CD3 alone induced comparable levels of IL-12R expression to those induced upon CD28 costimulation .", "annotated_text": "However , stimulation of <cell_type>T cells</cell_type> with high doses of <protein>anti-CD3</protein> alone induced comparable levels of <protein>IL-12R</protein> expression to those induced upon CD28 costimulation ."}
{"id": "1689", "text": "Nevertheless , there was a substantial difference in IL-12 responsiveness between these two groups of T cells : compared to anti-CD28-costimulated T cells , T cells that were not costimulated with anti-CD28 exhibited decreased levels of Janus kinases ( JAK ) JAK2/TYK2 and STAT4 phosphorylation and IFN-y production following IL-12 stimulation .", "annotated_text": "Nevertheless , there was a substantial difference in <protein>IL-12</protein> responsiveness between these two groups of <cell_type>T cells</cell_type> : compared to <cell_type>anti-CD28-costimulated T cells</cell_type> , <cell_type>T cells</cell_type> that were not costimulated with <protein>anti-CD28</protein> exhibited decreased levels of <protein>Janus kinases</protein> ( <protein>JAK</protein> ) <protein>JAK2/TYK2</protein> and <protein>STAT4</protein> phosphorylation and IFN-y production following <protein>IL-12</protein> stimulation ."}
{"id": "1690", "text": "Importantly , STAT6 phosphorylation following IL-4 stimulation was not decreased in anti-CD28-uncostimulated T cells .", "annotated_text": "Importantly , STAT6 phosphorylation following IL-4 stimulation was not decreased in <cell_type>anti-CD28-uncostimulated T cells</cell_type> ."}
{"id": "1691", "text": "These resutls indicate that CD28 costimulation not only contributes to up-regulating IL-12R expression but is also required to render JAKs/STAT4 responsive to IL-12 stimulation .", "annotated_text": "These resutls indicate that CD28 costimulation not only contributes to up-regulating <protein>IL-12R</protein> expression but is also required to render <protein>JAKs/STAT4</protein> responsive to <protein>IL-12</protein> stimulation ."}
{"id": "1692", "text": "Constitutively activated Akt-1 is vital for the survival of human monocyte-differentiated macrophages .", "annotated_text": "Constitutively activated <protein>Akt-1</protein> is vital for the survival of <cell_type>human monocyte-differentiated macrophages</cell_type> ."}
{"id": "1693", "text": "Role of Mcl-1 , independent of nuclear factor ( NF ) -kappaB , Bad , or caspase activation .", "annotated_text": "Role of <protein>Mcl-1</protein> , independent of <protein>nuclear factor ( NF ) -kappaB</protein> , <protein>Bad</protein> , or caspase activation ."}
{"id": "1694", "text": "Recent data from mice deficient for phosphatase and tensin homologue deleted from chromosome 10 or src homology 2 domain-containing 5 ' inositol phosphatase , phosphatases that negatively regulate the phosphatidylinositol 3-kinase ( PI3K ) pathway , revealed an increased number of macrophages in these animals , suggesting an essential role for the PI3K pathway for macro-phage survival .", "annotated_text": "Recent data from mice deficient for <protein>phosphatase</protein> and <dna>tensin homologue</dna> deleted from <dna>chromosome 10</dna> or <protein>src homology 2 domain-containing 5 ' inositol phosphatase</protein> , <protein>phosphatases</protein> that negatively regulate the <protein>phosphatidylinositol 3-kinase</protein> ( <protein>PI3K</protein> ) pathway , revealed an increased number of <cell_type>macrophages</cell_type> in these animals , suggesting an essential role for the <protein>PI3K</protein> pathway for <cell_type>macro-phage</cell_type> survival ."}
{"id": "1695", "text": "Here , we focused on the role of the PI3K-regulated serine/threonine kinase Akt-1 in modulating macrophage survival .", "annotated_text": "Here , we focused on the role of the <protein>PI3K-regulated serine/threonine kinase</protein> <protein>Akt-1</protein> in modulating <cell_type>macrophage</cell_type> survival ."}
{"id": "1696", "text": "Akt-1 was constitutively activated in human macrophages and addition of the PI3K inhibitor , LY294002 , suppressed the activation of Akt-1 and induced cell death .", "annotated_text": "<protein>Akt-1</protein> was constitutively activated in <cell_type>human macrophages</cell_type> and addition of the <protein>PI3K</protein> inhibitor , LY294002 , suppressed the activation of <protein>Akt-1</protein> and induced cell death ."}
{"id": "1697", "text": "Furthermore , suppression of Akt-1 by inhibition of PI3K or a dominant negative ( DN ) Akt-1 resulted in loss of mitochondrial transmembrane potential , activation of caspases-9 and -3 , and DNA fragmentation .", "annotated_text": "Furthermore , suppression of <protein>Akt-1</protein> by inhibition of <protein>PI3K</protein> or a <protein>dominant negative ( DN ) Akt-1</protein> resulted in loss of mitochondrial transmembrane potential , activation of <protein>caspases-9 and -3</protein> , and DNA fragmentation ."}
{"id": "1698", "text": "The effects of PI3K inhibition were reversed by the ectopic expression of constitutively activated Akt-1 or Bcl-x ( L ) .", "annotated_text": "The effects of <protein>PI3K</protein> inhibition were reversed by the ectopic expression of constitutively activated <protein>Akt-1</protein> or <protein>Bcl-x ( L )</protein> ."}
{"id": "1699", "text": "Inhibition of PI3K /Akt-1 pathway either by LY294002 or DN Akt-1 had no effect on the constitutive or inducible activation of nuclear factor ( NF ) -kappaB in human macrophages .", "annotated_text": "Inhibition of <protein>PI3K</protein> /Akt-1 pathway either by LY294002 or <protein>DN Akt-1</protein> had no effect on the constitutive or inducible activation of <protein>nuclear factor ( NF ) -kappaB</protein> in <cell_type>human macrophages</cell_type> ."}
{"id": "1700", "text": "However , after inhibition of the PI3K / Akt-1 pathway , a marked decrease in the expression of the antiapoptotic molecule Mcl-1 , but not other Bcl-2 family members was observed , and Mcl-1 rescued macrophages from LY294002-induced cell death .", "annotated_text": "However , after inhibition of the <protein>PI3K</protein> / <protein>Akt-1</protein> pathway , a marked decrease in the expression of the <protein>antiapoptotic molecule</protein> <protein>Mcl-1</protein> , but not other <protein>Bcl-2 family members</protein> was observed , and <protein>Mcl-1</protein> rescued <cell_type>macrophages</cell_type> from LY294002-induced cell death ."}
{"id": "1701", "text": "Further , inhibition of Mcl-1 by antisense oligonucleotides , also resulted in macrophage apoptosis .", "annotated_text": "Further , inhibition of <protein>Mcl-1</protein> by antisense oligonucleotides , also resulted in <cell_type>macrophage</cell_type> apoptosis ."}
{"id": "1702", "text": "Thus , our findings demonstrate that the constitutive activation of Akt-1 regulates macrophage survival through Mcl-1 , which is independent of caspases , NF-kappaB , or Bad .", "annotated_text": "Thus , our findings demonstrate that the constitutive activation of <protein>Akt-1</protein> regulates <cell_type>macrophage</cell_type> survival through <protein>Mcl-1</protein> , which is independent of <protein>caspases</protein> , <protein>NF-kappaB</protein> , or <protein>Bad</protein> ."}
{"id": "1703", "text": "GRbeta expression in nasal polyp inflammatory cells and its relationship to the anti-inflammatory effects of intranasal fluticasone .", "annotated_text": "GRbeta expression in <cell_type>nasal polyp inflammatory cells</cell_type> and its relationship to the anti-inflammatory effects of intranasal fluticasone ."}
{"id": "1704", "text": "BACKGROUND : Nasal polyposis disease is an inflammatory disorder with intense eosinophilic infiltration of respiratory mucosa that is often difficult to control with topical steroids .", "annotated_text": "BACKGROUND : Nasal polyposis disease is an inflammatory disorder with intense eosinophilic infiltration of respiratory mucosa that is often difficult to control with topical steroids ."}
{"id": "1705", "text": "Recent evidence suggests that overexpression of the glucocorticoid receptor splice variant GRbeta in inflammatory cells might contribute to steroid insensitivity in diseases such as asthma .", "annotated_text": "Recent evidence suggests that overexpression of the <protein>glucocorticoid receptor splice variant</protein> <protein>GRbeta</protein> in <cell_type>inflammatory cells</cell_type> might contribute to steroid insensitivity in diseases such as asthma ."}
{"id": "1706", "text": "OBJECTIVE : The purposes of this investigation were to determine whether nasal polyp ( NP ) inflammatory cells overexpress GRbeta and to examine whether GRbeta overexpression is associated with insensitivity to the potent topical steroid fluticasone propionate ( FP ) .", "annotated_text": "OBJECTIVE : The purposes of this investigation were to determine whether <cell_type>nasal polyp ( NP ) inflammatory cells</cell_type> overexpress <protein>GRbeta</protein> and to examine whether <protein>GRbeta</protein> overexpression is associated with insensitivity to the potent topical steroid fluticasone propionate ( FP ) ."}
{"id": "1707", "text": "METHODS : Biopsies were obtained from 10 subjects with NPs before and 4 weeks after treatment with intranasal FP .", "annotated_text": "METHODS : Biopsies were obtained from 10 subjects with NPs before and 4 weeks after treatment with intranasal FP ."}
{"id": "1708", "text": "Middle turbinates biopsies from 6 healthy , nonallergic subjects served as normal controls .", "annotated_text": "Middle turbinates biopsies from 6 healthy , nonallergic subjects served as normal controls ."}
{"id": "1709", "text": "Biopsies were immunostained for inflammatory cell markers as well as GRbeta and probed for various cytokine mRNA .", "annotated_text": "Biopsies were immunostained for inflammatory cell markers as well as <protein>GRbeta</protein> and probed for various <rna>cytokine mRNA</rna> ."}
{"id": "1710", "text": "The anti-inflammatory response to FP was examined in relation to pretreatment levels of GRbeta expression .", "annotated_text": "The anti-inflammatory response to FP was examined in relation to pretreatment levels of GRbeta expression ."}
{"id": "1711", "text": "RESULTS : The total numbers of inflammatory cells were increased in NPs .", "annotated_text": "RESULTS : The total numbers of <cell_type>inflammatory cells</cell_type> were increased in <cell_type>NPs</cell_type> ."}
{"id": "1712", "text": "The percentage of inflammatory cells expressing GRbeta was also increased ( 40.5 % +/- 19.2 % vs 16.1 % +/- 4.0 % , P =.009 ) .", "annotated_text": "The percentage of <cell_type>inflammatory cells</cell_type> expressing <protein>GRbeta</protein> was also increased ( 40.5 % +/- 19.2 % vs 16.1 % +/- 4.0 % , P =.009 ) ."}
{"id": "1713", "text": "GRbeta expression in NPs was almost exclusive to T lymphocytes , eosinophils , and macrophages .", "annotated_text": "<protein>GRbeta</protein> expression in <cell_type>NPs</cell_type> was almost exclusive to <cell_type>T lymphocytes</cell_type> , <cell_type>eosinophils</cell_type> , and <cell_type>macrophages</cell_type> ."}
{"id": "1714", "text": "An inverse correlation was observed between the baseline inflammatory cell GRbeta expression and the reduction after FP treatment in EG2-positive eosinophils , CD4-positive T lymphocytes , endothelial VCAM-1 expression , and IL-4 mRNA-positive cells .", "annotated_text": "An inverse correlation was observed between the baseline inflammatory cell <protein>GRbeta</protein> expression and the reduction after FP treatment in <cell_type>EG2-positive eosinophils</cell_type> , <cell_type>CD4-positive T lymphocytes</cell_type> , endothelial <protein>VCAM-1</protein> expression , and <cell_type>IL-4 mRNA-positive cells</cell_type> ."}
{"id": "1715", "text": "NPs that were `` FP-insensitive '' in terms of suppression of eosinophil numbers ( major basic protein -positive ) had a significantly greater percentage of GRbeta-positive inflammatory cells , a higher ratio of GRbeta-positive/GRalpha-positive cells , and increased numbers of GRbeta-positive eosinophils and macrophages in comparison with those that were `` FP-sensitive. ''", "annotated_text": "<cell_type>NPs</cell_type> that were `` FP-insensitive '' in terms of suppression of <cell_type>eosinophil</cell_type> numbers ( <protein>major basic protein</protein> -positive ) had a significantly greater percentage of <cell_type>GRbeta-positive inflammatory cells</cell_type> , a higher ratio of <cell_type>GRbeta-positive/GRalpha-positive cells</cell_type> , and increased numbers of <cell_type>GRbeta-positive eosinophils</cell_type> and <cell_type>macrophages</cell_type> in comparison with those that were `` FP-sensitive. ''"}
{"id": "1716", "text": "`` FP-insensitive '' NPs also demonstrated a higher percentage of IL-5-positive inflammatory cells expressing GRbeta before and after FP treatment .", "annotated_text": "<cell_type>`` FP-insensitive '' NPs</cell_type> also demonstrated a higher percentage of <cell_type>IL-5-positive inflammatory cells</cell_type> expressing <protein>GRbeta</protein> before and after FP treatment ."}
{"id": "1717", "text": "CONCLUSION : GRbeta expression appears to be a marker of steroid insensitivity in NPs .", "annotated_text": "CONCLUSION : <protein>GRbeta</protein> expression appears to be a marker of steroid insensitivity in <cell_type>NPs</cell_type> ."}
{"id": "1718", "text": "Expression of GRbeta by NP inflammatory cells , particularly T cells and eosinophils , might render them resistant to suppression by topical steroids and thereby contribute to persistent NP inflammation .", "annotated_text": "Expression of <protein>GRbeta</protein> by <cell_type>NP inflammatory cells</cell_type> , particularly <cell_type>T cells</cell_type> and <cell_type>eosinophils</cell_type> , might render them resistant to suppression by topical steroids and thereby contribute to persistent <cell_type>NP</cell_type> inflammation ."}
{"id": "1719", "text": "Transcriptional regulation of galectin-10 ( eosinophil Charcot-Leyden crystal protein ) : a GC box ( -44 to -50 ) controls butyric acid induction of gene expression .", "annotated_text": "Transcriptional regulation of <protein>galectin-10</protein> ( <protein>eosinophil Charcot-Leyden crystal protein</protein> ) : a <dna>GC box</dna> ( -44 to -50 ) controls butyric acid induction of gene expression ."}
{"id": "1720", "text": "Galectin-10 ( gal-10 , also known as Charcot-Leyden crystal protein ) is a member of the galectin family of beta-galactoside binding proteins that is expressed uniquely in eosinophilic and basophilic leukocytes .", "annotated_text": "<protein>Galectin-10</protein> ( <protein>gal-10</protein> , also known as <protein>Charcot-Leyden crystal protein</protein> ) is a member of the <protein>galectin family</protein> of <protein>beta-galactoside binding proteins</protein> that is expressed uniquely in <cell_type>eosinophilic and basophilic leukocytes</cell_type> ."}
{"id": "1721", "text": "To gain a better understanding of galectin gene expression , we present an analysis of the transcriptional regulation of the gene encoding gal-10 .", "annotated_text": "To gain a better understanding of galectin gene expression , we present an analysis of the transcriptional regulation of the gene encoding <protein>gal-10</protein> ."}
{"id": "1722", "text": "Analysis of the minimal promoter revealed nine consensus-binding sites for transcription factors , including several that are also found in the minimal promoters of galectins -1 , -2 , and -3 .", "annotated_text": "Analysis of the <dna>minimal promoter</dna> revealed nine <dna>consensus-binding sites</dna> for <protein>transcription factors</protein> , including several that are also found in the <dna>minimal promoters</dna> of <dna>galectins -1 , -2 , and -3</dna> ."}
{"id": "1723", "text": "The decrease in gal-10 promoter activity after disruption of either the GC box ( -44 to -50 ) or the Oct site ( -255 to -261 ) suggests that these sites , along with the previously characterized GATA and EoTF sites , are necessary for full promoter activity .", "annotated_text": "The decrease in gal-10 promoter activity after disruption of either the <dna>GC box</dna> ( -44 to -50 ) or the <dna>Oct site</dna> ( -255 to -261 ) suggests that these sites , along with the previously characterized <dna>GATA and EoTF sites</dna> , are necessary for full promoter activity ."}
{"id": "1724", "text": "By supershift analysis , we demonstrate binding of the transcription factors Sp1 and Oct1 to the consensus GC box and the Oct site , respectively .", "annotated_text": "By supershift analysis , we demonstrate binding of the <protein>transcription factors</protein> <protein>Sp1</protein> and <protein>Oct1</protein> to the <dna>consensus GC box</dna> and the <dna>Oct site</dna> , respectively ."}
{"id": "1725", "text": "Similar to gal-1 , gal-10 expression is induced by butyric acid , an effect that is lost upon ablation of the GC box .", "annotated_text": "Similar to <dna>gal-1</dna> , gal-10 expression is induced by butyric acid , an effect that is lost upon ablation of the <dna>GC box</dna> ."}
{"id": "1726", "text": "Additionally , we demonstrate AML3 binding to the consensus AML site and YY1 binding to the Inr sequence , both elements functioning as silencers in the gal-10 promoter .", "annotated_text": "Additionally , we demonstrate AML3 binding to the <dna>consensus AML site</dna> and <protein>YY1 binding</protein> to the <dna>Inr sequence</dna> , both elements functioning as silencers in the <dna>gal-10 promoter</dna> ."}
{"id": "1727", "text": "Tumour-stromal interactions .", "annotated_text": "Tumour-stromal interactions ."}
{"id": "1728", "text": "Role of the stroma in mammary development .", "annotated_text": "Role of the stroma in mammary development ."}
{"id": "1729", "text": "Mammary development depends on branching morphogenesis , namely the bifurcation and extension of ductal growth points ( end buds ) and secretory lobules into a more or less fatty stroma .", "annotated_text": "Mammary development depends on branching morphogenesis , namely the bifurcation and extension of ductal growth points ( end buds ) and secretory lobules into a more or less fatty stroma ."}
{"id": "1730", "text": "Because breast carcinomas are overwhelmingly ductal in origin , this review focuses on stromal influences guiding postnatal ductal development and there is only the briefest account of the role of embryonic stroma ( mesenchyme ) .", "annotated_text": "Because breast carcinomas are overwhelmingly ductal in origin , this review focuses on stromal influences guiding postnatal ductal development and there is only the briefest account of the role of embryonic stroma ( mesenchyme ) ."}
{"id": "1731", "text": "The stroma as the necessary target for endocrine mammogens and the source of stimulatory growth factors is described and the importance of mammary epithelium-induced modifications of the periductal stroma is emphasized .", "annotated_text": "The stroma as the necessary target for endocrine mammogens and the source of stimulatory growth factors is described and the importance of mammary epithelium-induced modifications of the periductal stroma is emphasized ."}
{"id": "1732", "text": "Evidence is presented that if they are to grow , end buds must condition proximal fatty stroma by recruiting white blood cells as well as inducing stromal cell division and , possibly , estrogen receptors .", "annotated_text": "Evidence is presented that if they are to grow , end buds must condition proximal fatty stroma by recruiting <cell_type>white blood cells</cell_type> as well as inducing stromal cell division and , possibly , <protein>estrogen receptors</protein> ."}
{"id": "1733", "text": "The induction of a fibrous stromal tunic around the end bud is described and its likely role as a complex ductal morphogen is discussed ; a possible role in growth inhibition is also considered .", "annotated_text": "The induction of a fibrous stromal tunic around the end bud is described and its likely role as a complex ductal morphogen is discussed ; a possible role in growth inhibition is also considered ."}
{"id": "1734", "text": "Although the signals governing fibrotic induction , ductal morphogenesis , and growth inhibition are unknown , a role for transforming growth factor-beta is highly likely and is discussed .", "annotated_text": "Although the signals governing fibrotic induction , ductal morphogenesis , and growth inhibition are unknown , a role for transforming <protein>growth factor-beta</protein> is highly likely and is discussed ."}
{"id": "1735", "text": "Finally , a need for new conceptual and experimental approaches to understanding stromal-epithelial signaling is discussed .", "annotated_text": "Finally , a need for new conceptual and experimental approaches to understanding stromal-epithelial signaling is discussed ."}
{"id": "1736", "text": "Adipophilin is a sensitive marker for lipid loading in human blood monocytes .", "annotated_text": "<protein>Adipophilin</protein> is a sensitive marker for lipid loading in <cell_type>human blood monocytes</cell_type> ."}
{"id": "1737", "text": "Adipophilin , a marker of lipid accumulation initially described in adipocytes , was recently shown to be induced in macrophage foam cells .", "annotated_text": "<protein>Adipophilin</protein> , a marker of lipid accumulation initially described in <cell_type>adipocytes</cell_type> , was recently shown to be induced in <cell_type>macrophage foam cells</cell_type> ."}
{"id": "1738", "text": "We found that even freshly isolated blood monocytes express adipophilin and that the amount of adipophilin protein is variable in monocytes from different healthy individuals .", "annotated_text": "We found that even <cell_type>freshly isolated blood monocytes</cell_type> express <protein>adipophilin</protein> and that the amount of <protein>adipophilin protein</protein> is variable in <cell_type>monocytes</cell_type> from different healthy individuals ."}
{"id": "1739", "text": "However , the physiological expression of adipophilin does not correlate with the levels of free fatty acids , cholesterylesters or free cholesterol .", "annotated_text": "However , the physiological expression of <protein>adipophilin</protein> does not correlate with the levels of free fatty acids , cholesterylesters or free cholesterol ."}
{"id": "1740", "text": "Enzymatically modified low-density lipoprotein ( E-LDL ) induces rapid foam cell formation in monocytes and upregulates adipophilin mRNA and protein within 2 h of incubation .", "annotated_text": "<protein>Enzymatically modified low-density lipoprotein</protein> ( <protein>E-LDL</protein> ) induces rapid foam cell formation in <cell_type>monocytes</cell_type> and upregulates <protein>adipophilin</protein> mRNA and protein within 2 h of incubation ."}
{"id": "1741", "text": "This rapid induction of adipophilin is accompanied by a significant increase of free fatty acids in monocytes incubated with E-LDL .", "annotated_text": "This rapid induction of <protein>adipophilin</protein> is accompanied by a significant increase of free fatty acids in <cell_type>monocytes</cell_type> incubated with <protein>E-LDL</protein> ."}
{"id": "1742", "text": "Adipophilin facilitates the uptake of free fatty acids , and here we demonstrate that free fatty acids increase is related to the early upregulation of adipophilin expression in blood monocytes .", "annotated_text": "<protein>Adipophilin</protein> facilitates the uptake of free fatty acids , and here we demonstrate that free fatty acids increase is related to the early upregulation of adipophilin expression in <cell_type>blood monocytes</cell_type> ."}
{"id": "1743", "text": "Fatty acids are ligands for peroxisome proliferator-activated receptor-gamma ( PPARgamma ) , and the upregulation of adipophilin mRNA by PPARgamma agonists like 15d-PGJ ( 2 ) and ciglitazone indicates that PPARgamma may mediate the induction of adipophilin expression in human blood monocytes .", "annotated_text": "Fatty acids are ligands for <protein>peroxisome proliferator-activated receptor-gamma</protein> ( <protein>PPARgamma</protein> ) , and the upregulation of <rna>adipophilin mRNA</rna> by <protein>PPARgamma</protein> agonists like 15d-PGJ ( 2 ) and ciglitazone indicates that <protein>PPARgamma</protein> may mediate the induction of adipophilin expression in <cell_type>human blood monocytes</cell_type> ."}
{"id": "1744", "text": "Constitutive expression of MHC class II genes in melanoma cell lines results from the transcription of class II transactivator abnormally initiated from its B cell-specific promoter .", "annotated_text": "Constitutive expression of <dna>MHC class II genes</dna> in <cell_line>melanoma cell lines</cell_line> results from the transcription of <dna>class II transactivator</dna> abnormally initiated from its <dna>B cell-specific promoter</dna> ."}
{"id": "1745", "text": "In melanoma cell lines , two different patterns of MHC class II expression have been described , either an IFN gamma-inducible expression of HLA-DR and HLA-DP , with a faint or null expression of HLA-DQ , resembling that described for melanocytes , or a constitutive expression , i.e. , IFN-gamma independent , of all three HLA-D isotypes .", "annotated_text": "In <cell_line>melanoma cell lines</cell_line> , two different patterns of MHC class II expression have been described , either an IFN gamma-inducible expression of <dna>HLA-DR</dna> and <dna>HLA-DP</dna> , with a faint or null expression of <dna>HLA-DQ</dna> , resembling that described for <cell_type>melanocytes</cell_type> , or a constitutive expression , i.e. , IFN-gamma independent , of all three <dna>HLA-D isotypes</dna> ."}
{"id": "1746", "text": "As this latter phenotype has been associated with a more rapid progression of melanoma tumors , we have analyzed in different melanoma cell lines the molecular mechanisms leading to this abnormal pattern of MHC class II expression .", "annotated_text": "As this latter phenotype has been associated with a more rapid progression of melanoma tumors , we have analyzed in different <cell_line>melanoma cell lines</cell_line> the molecular mechanisms leading to this abnormal pattern of MHC class II expression ."}
{"id": "1747", "text": "In agreement with the evidence of a coordinate transcription of the HLA-D genes in these cell lines , we have shown the constitutive expression of CIITA ( class II transactivator ) transcripts , CIITA being known as the master switch of MHC class II expression .", "annotated_text": "In agreement with the evidence of a coordinate transcription of the <dna>HLA-D genes</dna> in these cell lines , we have shown the constitutive expression of <rna>CIITA ( class II transactivator ) transcripts</rna> , <protein>CIITA</protein> being known as the master switch of MHC class II expression ."}
{"id": "1748", "text": "Unexpectedly , these transcripts initiate from promoter III of the CIITA gene , a promoter that is mainly used constitutively in B lymphocytes .", "annotated_text": "Unexpectedly , these transcripts initiate from <dna>promoter III</dna> of the <dna>CIITA gene</dna> , a promoter that is mainly used constitutively in <cell_type>B lymphocytes</cell_type> ."}
{"id": "1749", "text": "This expression was further shown to occur through factor ( s ) acting on the enhancer located upstream of CIITA promoter III , which was previously described in epithelioid cells as an IFN-gamma-response sequence .", "annotated_text": "This expression was further shown to occur through factor ( s ) acting on the enhancer located upstream of <dna>CIITA promoter III</dna> , which was previously described in <cell_type>epithelioid cells</cell_type> as an IFN-gamma-response sequence ."}
{"id": "1750", "text": "The hypothesis of a general abnormality of the IFN-gamma transduction pathway was dismissed .", "annotated_text": "The hypothesis of a general abnormality of the IFN-gamma transduction pathway was dismissed ."}
{"id": "1751", "text": "Constitutive transcription of CIITA from promoter III having been observed in unrelated melanoma cell lines , we propose the hypothesis that this phenomenon might not be a random event , but could be linked to the neoplasic state of the melanoma cells", "annotated_text": "Constitutive transcription of <dna>CIITA</dna> from <dna>promoter III</dna> having been observed in unrelated <cell_line>melanoma cell lines</cell_line> , we propose the hypothesis that this phenomenon might not be a random event , but could be linked to the neoplasic state of the <cell_type>melanoma cells</cell_type>"}
{"id": "1752", "text": "Caspase -mediated calcineurin activation contributes to IL-2 release during T cell activation .", "annotated_text": "<protein>Caspase</protein> -mediated calcineurin activation contributes to <protein>IL-2</protein> release during T cell activation ."}
{"id": "1753", "text": "Calcineurin , a Ca ( 2+ ) /calmodulin-dependent Ser/Thr phosphatase ( protein phosphatase 2B ) , plays a critical role in IL-2 production during T cell activation .", "annotated_text": "<protein>Calcineurin</protein> , a <protein>Ca ( 2+ ) /calmodulin-dependent Ser/Thr phosphatase ( protein phosphatase 2B )</protein> , plays a critical role in IL-2 production during T cell activation ."}
{"id": "1754", "text": "It has been previously reported that IL-2 release in activated Jurkat T requires caspase-like activity ( Posmantur et al. ( 1998 ) Exp. Cell. Res. 244 , 302-309 ) .", "annotated_text": "It has been previously reported that <protein>IL-2</protein> release in activated <cell_line>Jurkat T</cell_line> requires caspase-like activity ( Posmantur et al. ( 1998 ) Exp. Cell. Res. 244 , 302-309 ) ."}
{"id": "1755", "text": "We report here that the 60-kDa catalytic subunit of calcineurin A ( Cn A ) was partially cleaved to a 45-kDa form in phytohemagglutinin A ( PHA ) or phorbol ester + ionomycin ( P + I ) -activated Jurkat cells .", "annotated_text": "We report here that the <protein>60-kDa catalytic subunit</protein> of <protein>calcineurin A</protein> ( <protein>Cn A</protein> ) was partially cleaved to a <protein>45-kDa</protein> form in phytohemagglutinin A ( PHA ) or phorbol ester + ionomycin ( P + I ) -activated <cell_line>Jurkat cells</cell_line> ."}
{"id": "1756", "text": "In parallel , proteolytic activation of upstream caspases ( caspase-8 and -9 ) as well as effector caspase-3 was also observed .", "annotated_text": "In parallel , proteolytic activation of upstream <protein>caspases</protein> ( caspase-8 and -9 ) as well as <protein>effector caspase-3</protein> was also observed ."}
{"id": "1757", "text": "Cn A cleavage was caspase mediated , since it was inhibitable by pan-caspase inhibitor Cbz-Asp-CH ( 2 ) OC ( O ) -2 , 6-dichlorobenzene ( Z-D-DCB ) .", "annotated_text": "<protein>Cn A</protein> cleavage was caspase mediated , since it was inhibitable by pan-caspase inhibitor Cbz-Asp-CH ( 2 ) OC ( O ) -2 , 6-dichlorobenzene ( Z-D-DCB ) ."}
{"id": "1758", "text": "Cn A cleavage was also observed when purified calcineurin was digested in vitro with caspase-3 .", "annotated_text": "<protein>Cn A</protein> cleavage was also observed when purified <protein>calcineurin</protein> was digested in vitro with <protein>caspase-3</protein> ."}
{"id": "1759", "text": "Truncated Cn A was associated with enhanced phosphatase activity and reduced calmodulin sensitivity .", "annotated_text": "<protein>Truncated Cn A</protein> was associated with enhanced phosphatase activity and reduced calmodulin sensitivity ."}
{"id": "1760", "text": "Furthermore , in PHA or P + I-activated Jurkat cells , dephosphorylation of calcineurin substrate NFATc ( a transcription factor known to be involved in transactivation of the IL-2 gene ) , was also suppressed by Z-D-DCB .", "annotated_text": "Furthermore , in PHA or P + I-activated <cell_line>Jurkat cells</cell_line> , dephosphorylation of <protein>calcineurin</protein> substrate <protein>NFATc</protein> ( a <protein>transcription factor</protein> known to be involved in transactivation of the <dna>IL-2 gene</dna> ) , was also suppressed by Z-D-DCB ."}
{"id": "1761", "text": "Taken together , our results suggest that caspase-mediated cleavage of Cn A contributes to IL-2 production during T cell activation .", "annotated_text": "Taken together , our results suggest that caspase-mediated cleavage of <protein>Cn A</protein> contributes to IL-2 production during T cell activation ."}
{"id": "1762", "text": "Copyright 2001 Academic Press .", "annotated_text": "Copyright 2001 Academic Press ."}
{"id": "1763", "text": "Maturation of human dendritic cells as sulfasalazine target .", "annotated_text": "Maturation of <cell_type>human dendritic cells</cell_type> as sulfasalazine target ."}
{"id": "1764", "text": "AIM : Sulfasalazine , a nonsteroidal anti-inflammatory drug , is effective in treating some autoimmune diseases , but its mechanism of action is unclear .", "annotated_text": "AIM : Sulfasalazine , a nonsteroidal anti-inflammatory drug , is effective in treating some autoimmune diseases , but its mechanism of action is unclear ."}
{"id": "1765", "text": "To determine whether dendritic cells could be a possible target of the drug , we studied the effects of sulfasalazine and its metabolites , aminosalicylate and sulfapyridine , on in vitro maturation ( terminal differentiation ) of human myeloid dendritic cells .", "annotated_text": "To determine whether <cell_type>dendritic cells</cell_type> could be a possible target of the drug , we studied the effects of sulfasalazine and its metabolites , aminosalicylate and sulfapyridine , on in vitro maturation ( terminal differentiation ) of <cell_type>human myeloid dendritic cells</cell_type> ."}
{"id": "1766", "text": "METHODS : We prepared immature dendritic cells by incubating CD14-positive cells in the presence of granulocyte- macrophage colony-stimulating factor and interleukin ( IL ) -4 .", "annotated_text": "METHODS : We prepared <cell_type>immature dendritic cells</cell_type> by incubating <cell_type>CD14-positive cells</cell_type> in the presence of <protein>granulocyte- macrophage colony-stimulating factor</protein> and <protein>interleukin ( IL ) -4</protein> ."}
{"id": "1767", "text": "The cells were matured by addition of tumor necrosis factor ( TNF ) -a , IL-1 beta , and prostaglandin E2 in the presence of sulfasalazine or its metabolites -- aminosalicylate and sulfapyridine , or their combinations .", "annotated_text": "The cells were matured by addition of <protein>tumor necrosis factor ( TNF ) -a</protein> , <protein>IL-1 beta</protein> , and <protein>prostaglandin E2</protein> in the presence of sulfasalazine or its metabolites -- aminosalicylate and sulfapyridine , or their combinations ."}
{"id": "1768", "text": "We quantified the effect of drugs on the dendritic cell characteristics , such as stimulation of autologous and allogeneic pan-T cell proliferation , surface marker phenotype , IL-12 p40 subunit secretion , and activation of nuclear transcription factor ( NF ) -kappa B .", "annotated_text": "We quantified the effect of drugs on the dendritic cell characteristics , such as stimulation of autologous and allogeneic pan-T cell proliferation , surface marker phenotype , IL-12 p40 subunit secretion , and activation of <protein>nuclear transcription factor ( NF ) -kappa B</protein> ."}
{"id": "1769", "text": "RESULTS : Dendritic cells treated with sulfasalazine ( 1.25 micromol/L or 2.5 micromol/L ) could not stimulate T cells ( p < 0.028 , two-sided paired t-test ) .", "annotated_text": "RESULTS : <cell_type>Dendritic cells</cell_type> treated with sulfasalazine ( 1.25 micromol/L or 2.5 micromol/L ) could not stimulate <cell_type>T cells</cell_type> ( p < 0.028 , two-sided paired t-test ) ."}
{"id": "1770", "text": "In distinction to drug-free maturing dendritic cells , 2.5 micromol/L sulfasalazine upregulated the levels of CD14 and CD68 and downregulated the levels of CD40 , CD80 , and CD83 ( for all CD markers , p < 0.03 for difference between measurements in the absence and the presence of sulfasalazine ) .", "annotated_text": "In distinction to drug-free maturing <cell_type>dendritic cells</cell_type> , 2.5 micromol/L sulfasalazine upregulated the levels of <protein>CD14</protein> and <protein>CD68</protein> and downregulated the levels of <protein>CD40</protein> , <protein>CD80</protein> , and <protein>CD83</protein> ( for all CD markers , p < 0.03 for difference between measurements in the absence and the presence of sulfasalazine ) ."}
{"id": "1771", "text": "From concentration-dependent changes in CD83 expression , we found an apparent ID50 > > 1.5 micromol/L sulfasalazine .", "annotated_text": "From concentration-dependent changes in CD83 expression , we found an apparent ID50 > > 1.5 micromol/L sulfasalazine ."}
{"id": "1772", "text": "The apparent ID50 value for aminosalicylate-inhibited maturation was 4 micromol/L .", "annotated_text": "The apparent ID50 value for aminosalicylate-inhibited maturation was 4 micromol/L ."}
{"id": "1773", "text": "Sulfapyridine had no effect .", "annotated_text": "Sulfapyridine had no effect ."}
{"id": "1774", "text": "At 1.25 micromol/L , sulfasalazine largely inhibited NF-kB activation in dendritic cells .", "annotated_text": "At 1.25 micromol/L , sulfasalazine largely inhibited NF-kB activation in <cell_type>dendritic cells</cell_type> ."}
{"id": "1775", "text": "CONCLUSION : Maturing human dendritic cells are hundred-fold more sensitive to sulfasalazine than T cells and NK cells and the most sensitive human cells described so far .", "annotated_text": "CONCLUSION : <cell_type>Maturing human dendritic cells</cell_type> are hundred-fold more sensitive to sulfasalazine than <cell_type>T cells</cell_type> and <cell_type>NK cells</cell_type> and the most sensitive human cells described so far ."}
{"id": "1776", "text": "Thus , dendritic cell maturation is an important target of sulfasalazine .", "annotated_text": "Thus , dendritic cell maturation is an important target of sulfasalazine ."}
{"id": "1777", "text": "Because of the role of dendritic cells in ( auto ) immunity , inhibition of their maturation might provide a target for further optimization of sulfasalazine therapy .", "annotated_text": "Because of the role of <cell_type>dendritic cells</cell_type> in ( auto ) immunity , inhibition of their maturation might provide a target for further optimization of sulfasalazine therapy ."}
{"id": "1778", "text": "Defective function of the proteasome in autoimmunity : involvement of impaired NF-kappaB activation .", "annotated_text": "Defective function of the <protein>proteasome</protein> in autoimmunity : involvement of impaired NF-kappaB activation ."}
{"id": "1779", "text": "Type 1 diabetes ( also known as insulin-dependent diabetes mellitus or juvenile-onset diabetes ) is usually caused by T cell-mediated autoimmunity , with a prediabetic state characterized by the production of autoantibodies specific for proteins expressed by pancreatic beta cells .", "annotated_text": "Type 1 diabetes ( also known as insulin-dependent diabetes mellitus or juvenile-onset diabetes ) is usually caused by T cell-mediated autoimmunity , with a prediabetic state characterized by the production of <protein>autoantibodies</protein> specific for proteins expressed by <cell_type>pancreatic beta cells</cell_type> ."}
{"id": "1780", "text": "The nonobese patient with diabetes ( NOD ) mouse is a spontaneous model of type 1 diabetes with a strong genetic component that maps to the major histocompatibility complex ( MHC ) region of the genome .", "annotated_text": "The nonobese patient with diabetes ( NOD ) mouse is a spontaneous model of type 1 diabetes with a strong genetic component that maps to the <dna>major histocompatibility complex ( MHC ) region</dna> of the <dna>genome</dna> ."}
{"id": "1781", "text": "A specific proteasome defect has been identified in NOD mouse in select lymphocytic and monocytic lineages that results from down-regulation of expression of the proteasome subunit LMP2 , which is encoded by a gene in the MHC genomic region .", "annotated_text": "A specific <protein>proteasome</protein> defect has been identified in NOD mouse in select <cell_line>lymphocytic and monocytic lineages</cell_line> that results from down-regulation of expression of the <protein>proteasome subunit LMP2</protein> , which is encoded by a gene in the <dna>MHC genomic region</dna> ."}
{"id": "1782", "text": "This defect prevents the proteolytic processing required for the production and activation of the transcription factor nuclear factor-kappaB ( NF-kappaB ) , which plays important roles in immune and inflammatory responses , as well as increases the susceptibility of the affected cells to apoptosis induced by tumor necrosis factor-alpha ( TNF-alpha ) .", "annotated_text": "This defect prevents the proteolytic processing required for the production and activation of the <protein>transcription factor nuclear factor-kappaB</protein> ( <protein>NF-kappaB</protein> ) , which plays important roles in immune and inflammatory responses , as well as increases the susceptibility of the affected cells to apoptosis induced by <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) ."}
{"id": "1783", "text": "The novel role of the proteasome in dysfunction in autoimmunity is presented and documented to be both tissue and developmental stage specific .", "annotated_text": "The novel role of the <protein>proteasome</protein> in dysfunction in autoimmunity is presented and documented to be both tissue and developmental stage specific ."}
{"id": "1784", "text": "We propose a role of the proteasome as a step in disease pathogenesis and tissue targeting .", "annotated_text": "We propose a role of the <protein>proteasome</protein> as a step in disease pathogenesis and tissue targeting ."}
{"id": "1785", "text": "Down-regulation of TDT transcription in CD4 ( + ) CD8 ( + ) thymocytes by Ikaros proteins in direct competition with an Ets activator .", "annotated_text": "Down-regulation of TDT transcription in <cell_type>CD4 ( + ) CD8 ( + ) thymocytes</cell_type> by <protein>Ikaros proteins</protein> in direct competition with an <protein>Ets activator</protein> ."}
{"id": "1786", "text": "Ikaros is a unique regulator of lymphopoiesis that associates with pericentromeric heterochromatin and has been implicated in heritable gene inactivation .", "annotated_text": "<protein>Ikaros</protein> is a unique regulator of lymphopoiesis that associates with <dna>pericentromeric heterochromatin</dna> and has been implicated in heritable gene inactivation ."}
{"id": "1787", "text": "Binding and competition experiments demonstrate that Ikaros dimers compete with an Ets activator for occupancy of the lymphocyte-specific TdT promoter .", "annotated_text": "Binding and competition experiments demonstrate that <protein>Ikaros dimers</protein> compete with an <protein>Ets activator</protein> for occupancy of the <dna>lymphocyte-specific TdT promoter</dna> ."}
{"id": "1788", "text": "Mutations that selectively disrupt Ikaros binding to an integrated TdT promoter had no effect on promoter function in a CD4 ( + ) CD8 ( + ) thymocyte line .", "annotated_text": "Mutations that selectively disrupt Ikaros binding to an <dna>integrated TdT promoter</dna> had no effect on promoter function in a <cell_line>CD4 ( + ) CD8 ( + ) thymocyte line</cell_line> ."}
{"id": "1789", "text": "However , these mutations abolished down-regulation on differentiation , providing evidence that Ikaros plays a direct role in repression .", "annotated_text": "However , these mutations abolished down-regulation on differentiation , providing evidence that <protein>Ikaros</protein> plays a direct role in repression ."}
{"id": "1790", "text": "Reduced access to restriction enzyme cleavage suggested that chromatin alterations accompany down-regulation .", "annotated_text": "Reduced access to restriction enzyme cleavage suggested that chromatin alterations accompany down-regulation ."}
{"id": "1791", "text": "The Ikaros-dependent down-regulation event and the observed chromatin alterations appear to precede pericentromeric repositioning .", "annotated_text": "The Ikaros-dependent down-regulation event and the observed chromatin alterations appear to precede pericentromeric repositioning ."}
{"id": "1792", "text": "Current models propose that the functions of Ikaros should be disrupted by a small isoform that retains the dimerization domain and lacks the DNA-binding domain .", "annotated_text": "Current models propose that the functions of <protein>Ikaros</protein> should be disrupted by a small <protein>isoform</protein> that retains the <protein>dimerization domain</protein> and lacks the <protein>DNA-binding domain</protein> ."}
{"id": "1793", "text": "Surprisingly , in the CD4 ( + ) CD8 ( + ) thymocyte line , overexpression of a small Ikaros isoform had no effect on differentiation or on the pericentromeric targeting and DNA-binding properties of Ikaros .", "annotated_text": "Surprisingly , in the <cell_line>CD4 ( + ) CD8 ( + ) thymocyte line</cell_line> , overexpression of a <protein>small Ikaros isoform</protein> had no effect on differentiation or on the pericentromeric targeting and DNA-binding properties of <protein>Ikaros</protein> ."}
{"id": "1794", "text": "Rather , the small isoform assembled into multimeric complexes with DNA-bound Ikaros at the pericentromeric foci .", "annotated_text": "Rather , the small <protein>isoform</protein> assembled into <protein>multimeric complexes</protein> with <protein>DNA-bound Ikaros</protein> at the pericentromeric foci ."}
{"id": "1795", "text": "The capacity for in vivo multimer formation suggests that interactions between Ikaros dimers bound to the TdT promoter and those bound to pericentromeric repeat sequences may contribute to the pericentromeric repositioning of the inactive gene .", "annotated_text": "The capacity for in vivo multimer formation suggests that interactions between <protein>Ikaros dimers</protein> bound to the <dna>TdT promoter</dna> and those bound to <dna>pericentromeric repeat sequences</dna> may contribute to the pericentromeric repositioning of the <dna>inactive gene</dna> ."}
{"id": "1796", "text": "Type I interferons and IL-12 : convergence and cross-regulation among mediators of cellular immunity .", "annotated_text": "<protein>Type I interferons</protein> and <protein>IL-12</protein> : convergence and cross-regulation among mediators of cellular immunity ."}
{"id": "1797", "text": "Therapeutic use of type I IFN ( IFN-alpha/beta ) has become common .", "annotated_text": "Therapeutic use of <protein>type I IFN</protein> ( <protein>IFN-alpha/beta</protein> ) has become common ."}
{"id": "1798", "text": "Many of the diverse diseases targeted are marked by pathogenetic abnormalities in cell-mediated immunity ( CMI ) , these cellular immune responses either causing injury to the host , lacking sufficient vigor for virus or tumor clearance , or both .", "annotated_text": "Many of the diverse diseases targeted are marked by pathogenetic abnormalities in cell-mediated immunity ( CMI ) , these cellular immune responses either causing injury to the host , lacking sufficient vigor for virus or tumor clearance , or both ."}
{"id": "1799", "text": "In general , therapeutic efficacy is limited .", "annotated_text": "In general , therapeutic efficacy is limited ."}
{"id": "1800", "text": "It is thus notable that the pleiotropic effects of type I IFN on CMI remain poorly understood .", "annotated_text": "It is thus notable that the pleiotropic effects of <protein>type I IFN</protein> on CMI remain poorly understood ."}
{"id": "1801", "text": "We characterized the effects of type I IFN on the production of IL-12 , the central immunoregulatory cytokine of the CD4 ( + ) T cell arm of CMI .", "annotated_text": "We characterized the effects of <protein>type I IFN</protein> on the production of <protein>IL-12</protein> , the <protein>central immunoregulatory cytokine</protein> of the <protein>CD4 ( + ) T cell arm</protein> of CMI ."}
{"id": "1802", "text": "We show that type I IFN are potent inhibitors of IL-12 production by human monocytes/macrophages .", "annotated_text": "We show that <protein>type I IFN</protein> are potent inhibitors of IL-12 production by <cell_type>human monocytes/macrophages</cell_type> ."}
{"id": "1803", "text": "The underlying mechanism involves transcriptional inhibition of the IL-12p40 gene , marked by down-regulation of PU.1 binding activity at the upstream Ets site of the IL-12p40 promoter .", "annotated_text": "The underlying mechanism involves transcriptional inhibition of the <dna>IL-12p40 gene</dna> , marked by down-regulation of PU.1 binding activity at the <dna>upstream Ets site</dna> of the <dna>IL-12p40 promoter</dna> ."}
{"id": "1804", "text": "Type I IFN have previously been shown to be able to substitute for IL-12 in driving IFN-gamma production from T and NK cells .", "annotated_text": "<protein>Type I IFN</protein> have previously been shown to be able to substitute for <protein>IL-12</protein> in driving IFN-gamma production from <cell_type>T and NK cells</cell_type> ."}
{"id": "1805", "text": "The ability of IFN-alpha/beta to suppress IL-12 production while up-regulating IFN-gamma production suggests a possible mechanistic basis for the difficulties of employing these cytokines in diseases involving abnormalities of CMI .", "annotated_text": "The ability of <protein>IFN-alpha/beta</protein> to suppress IL-12 production while up-regulating IFN-gamma production suggests a possible mechanistic basis for the difficulties of employing these <protein>cytokines</protein> in diseases involving abnormalities of CMI ."}
{"id": "1806", "text": "Nuclear factor-kappaB suppressive and inhibitor-kappaB stimulatory effects of troglitazone in obese patients with type 2 diabetes : evidence of an antiinflammatory action ?", "annotated_text": "<protein>Nuclear factor-kappaB</protein> suppressive and <protein>inhibitor-kappaB</protein> stimulatory effects of troglitazone in obese patients with type 2 diabetes : evidence of an antiinflammatory action ?"}
{"id": "1807", "text": "It has been shown recently that troglitazone exerts an anti-inflammatory effect , in vitro , and in experimental animals .", "annotated_text": "It has been shown recently that troglitazone exerts an anti-inflammatory effect , in vitro , and in experimental animals ."}
{"id": "1808", "text": "To test these properties in humans , we investigated the effect of troglitazone on the proinflammatory transcription factor nuclear factor-kappaB and its inhibitory protein IkappaB in mononuclear cells ( MNC ) and plasma soluble intracellular adhesion molecule-1 , monocyte chemoattractant protein-1 , plasminogen activator inhibitor-1 , and C-reactive protein .", "annotated_text": "To test these properties in humans , we investigated the effect of troglitazone on the <protein>proinflammatory transcription factor nuclear factor-kappaB</protein> and its <protein>inhibitory protein IkappaB</protein> in <cell_type>mononuclear cells</cell_type> ( <cell_type>MNC</cell_type> ) and <protein>plasma soluble intracellular adhesion molecule-1</protein> , <protein>monocyte chemoattractant protein-1</protein> , <protein>plasminogen activator inhibitor-1</protein> , and <protein>C-reactive protein</protein> ."}
{"id": "1809", "text": "We also examined the effect of troglitazone on reactive oxygen species generation , p47 ( phox ) subunit expression , 9-hydroxyoctadecadienoic acid ( 9-HODE ) , 13-HODE , o-tyrosine , and m-tyrosine in obese patients with type 2 diabetes .", "annotated_text": "We also examined the effect of troglitazone on reactive oxygen species generation , p47 ( phox ) subunit expression , 9-hydroxyoctadecadienoic acid ( 9-HODE ) , 13-HODE , o-tyrosine , and m-tyrosine in obese patients with type 2 diabetes ."}
{"id": "1810", "text": "Seven obese patients with type 2 diabetes were treated with troglitazone ( 400 mg/day ) for 4 weeks .", "annotated_text": "Seven obese patients with type 2 diabetes were treated with troglitazone ( 400 mg/day ) for 4 weeks ."}
{"id": "1811", "text": "Blood samples were obtained at weekly intervals .", "annotated_text": "Blood samples were obtained at weekly intervals ."}
{"id": "1812", "text": "Nuclear factor-kappaB binding activity in MNC nuclear extracts was significantly inhibited after troglitazone treatment at week 1 and continued to be inhibited up to week 4 .", "annotated_text": "<protein>Nuclear factor-kappaB</protein> binding activity in <cell_type>MNC</cell_type> nuclear extracts was significantly inhibited after troglitazone treatment at week 1 and continued to be inhibited up to week 4 ."}
{"id": "1813", "text": "On the other hand , IkappaB protein levels increased significantly after troglitazone treatment at week 1 , and this increase persisted throughout the study .", "annotated_text": "On the other hand , IkappaB protein levels increased significantly after troglitazone treatment at week 1 , and this increase persisted throughout the study ."}
{"id": "1814", "text": "Plasma monocyte chemoattractant protein-1 and soluble intracellular adhesion molecule-1 concentrations did not decrease significantly after troglitazone treatment , although there was a trend toward inhibition .", "annotated_text": "<protein>Plasma monocyte chemoattractant protein-1</protein> and <protein>soluble intracellular adhesion molecule-1</protein> concentrations did not decrease significantly after troglitazone treatment , although there was a trend toward inhibition ."}
{"id": "1815", "text": "Reactive oxygen species generation by polymorphonuclear cells and MNC , p47 ( phox ) subunit protein quantities , plasminogen activator inhibitor-1 , and C-reactive protein levels decreased significantly after troglitazone intake .", "annotated_text": "Reactive oxygen species generation by <cell_type>polymorphonuclear cells</cell_type> and <cell_type>MNC</cell_type> , <protein>p47 ( phox ) subunit protein</protein> quantities , <protein>plasminogen activator inhibitor-1</protein> , and <protein>C-reactive protein</protein> levels decreased significantly after troglitazone intake ."}
{"id": "1816", "text": "13-HODE/linoleic acid and 9-HODE/linoleic acid ratios also decreased after troglitazone intake .", "annotated_text": "13-HODE/linoleic acid and 9-HODE/linoleic acid ratios also decreased after troglitazone intake ."}
{"id": "1817", "text": "However , o-tyrosine/phenylalanine and m-tyrosine/phenylalanine ratios did not change significantly .", "annotated_text": "However , o-tyrosine/phenylalanine and m-tyrosine/phenylalanine ratios did not change significantly ."}
{"id": "1818", "text": "These data show that troglitazone has profound antiinflammatory effects in addition to antioxidant effects in obese type 2 diabetics ; these effects may be relevant to the recently described beneficial antiatherosclerotic effects of troglitazone at the vascular level .", "annotated_text": "These data show that troglitazone has profound antiinflammatory effects in addition to antioxidant effects in obese type 2 diabetics ; these effects may be relevant to the recently described beneficial antiatherosclerotic effects of troglitazone at the vascular level ."}
{"id": "1819", "text": "OX40 stimulation by gp34/OX40 ligand enhances productive human immunodeficiency virus type 1 infection .", "annotated_text": "OX40 stimulation by <protein>gp34/OX40 ligand</protein> enhances productive human immunodeficiency virus type 1 infection ."}
{"id": "1820", "text": "OX40 is a member of the tumor necrosis factor ( TNF ) receptor superfamily and known to be an important costimulatory molecule expressed on activated T cells .", "annotated_text": "<protein>OX40</protein> is a member of the <protein>tumor necrosis factor ( TNF ) receptor superfamily</protein> and known to be an important <protein>costimulatory molecule</protein> expressed on <cell_type>activated T cells</cell_type> ."}
{"id": "1821", "text": "To investigate the role of costimulation of OX40 in human immunodeficiency virus type 1 ( HIV-1 ) infection by its natural ligand , gp34 , the OX40-transfected ACH-2 cell line , ACH-2/OX40 , chronically infected with HIV-1 , was cocultured with paraformaldehyde ( PFA ) -fixed gp34-transfected mouse cell line , SV-T2/gp34 .", "annotated_text": "To investigate the role of costimulation of <protein>OX40</protein> in human immunodeficiency virus type 1 ( HIV-1 ) infection by its natural ligand , <protein>gp34</protein> , the <cell_line>OX40-transfected ACH-2 cell line , ACH-2/OX40</cell_line> , chronically infected with HIV-1 , was cocultured with paraformaldehyde ( PFA ) -fixed <cell_line>gp34-transfected mouse cell line , SV-T2/gp34</cell_line> ."}
{"id": "1822", "text": "The results showed that HIV-1 production was strongly induced .", "annotated_text": "The results showed that HIV-1 production was strongly induced ."}
{"id": "1823", "text": "This was followed by apparent apoptosis , and both processes were specifically inhibited by the gp34 -specific neutralizing monoclonal antibody 5A8 .", "annotated_text": "This was followed by apparent apoptosis , and both processes were specifically inhibited by the <protein>gp34</protein> -specific <protein>neutralizing monoclonal antibody 5A8</protein> ."}
{"id": "1824", "text": "Endogenous TNF alpha ( TNF-alpha ) and TNF-beta production were not involved in the enhanced HIV-1 production .", "annotated_text": "Endogenous <protein>TNF alpha</protein> ( <protein>TNF-alpha</protein> ) and <protein>TNF-beta</protein> production were not involved in the enhanced HIV-1 production ."}
{"id": "1825", "text": "Furthermore , enhanced HIV-1 transcription in gp34 -stimulated ACH-2/OX40 cells was dependent on the kappa B site of the HIV-1 long terminal repeat , and the OX40-gp34 interaction activated NF-kappa B consisting of p50 and p65 subunits .", "annotated_text": "Furthermore , enhanced HIV-1 transcription in <protein>gp34</protein> -stimulated <cell_line>ACH-2/OX40 cells</cell_line> was dependent on the <dna>kappa B site</dna> of the <dna>HIV-1 long terminal repeat</dna> , and the OX40-gp34 interaction activated <protein>NF-kappa B</protein> consisting of <protein>p50 and p65 subunits</protein> ."}
{"id": "1826", "text": "When primary activated CD4 ( + ) T cells acutely infected with HIV-1 ( NL4-3 ) ( CXCR4-using T-cell-line-tropic ) were cocultured with PFA-fixed gp34 ( + ) human T-cell leukemia virus type 1-bearing MT-2 cells or SV-T2/gp34 cells , HIV-1 production was also markedly enhanced .", "annotated_text": "When primary activated <cell_type>CD4 ( + ) T cells</cell_type> acutely infected with HIV-1 ( NL4-3 ) ( <cell_line>CXCR4-using T-cell-line-tropic</cell_line> ) were cocultured with PFA-fixed <cell_type>gp34 ( + ) human T-cell</cell_type> leukemia virus type 1-bearing <cell_line>MT-2 cells</cell_line> or <cell_line>SV-T2/gp34 cells</cell_line> , HIV-1 production was also markedly enhanced ."}
{"id": "1827", "text": "The enhancement was again significantly inhibited by 5A8 .", "annotated_text": "The enhancement was again significantly inhibited by <protein>5A8</protein> ."}
{"id": "1828", "text": "The present study first shows that OX40-gp34 interaction stimulates HIV-1 expression and suggests that OX40 triggering by gp34 may play an important role in enhancing HIV-1 production in both acutely and latently infected CD4 ( + ) T cells in vivo .", "annotated_text": "The present study first shows that OX40-gp34 interaction stimulates HIV-1 expression and suggests that OX40 triggering by <protein>gp34</protein> may play an important role in enhancing HIV-1 production in both acutely and latently infected <cell_type>CD4 ( + ) T cells</cell_type> in vivo ."}
{"id": "1829", "text": "Troglitazone , a PPARgamma ligand , inhibits osteopontin gene expression in human monocytes/macrophage THP-1 cells .", "annotated_text": "Troglitazone , a PPARgamma ligand , inhibits osteopontin gene expression in <cell_type>human monocytes/macrophage THP-1 cells</cell_type> ."}
{"id": "1830", "text": "Peroxizome proliferator-activated receptor-gamma ( PPARgamma ) is a member of the nuclear receptor family of transcription factors that regulate adipocyte differentiation .", "annotated_text": "<protein>Peroxizome proliferator-activated receptor-gamma</protein> ( <protein>PPARgamma</protein> ) is a member of the <protein>nuclear receptor family</protein> of <protein>transcription factors</protein> that regulate adipocyte differentiation ."}
{"id": "1831", "text": "Recent studies indicate that liganded PPARgamma not only promotes differentiation but also inhibits the activation of macrophages .", "annotated_text": "Recent studies indicate that <protein>liganded PPARgamma</protein> not only promotes differentiation but also inhibits the activation of <cell_type>macrophages</cell_type> ."}
{"id": "1832", "text": "Osteopontin , a component of extracellular matrix , is synthesized by macrophages in atherosclerotic plaques .", "annotated_text": "<protein>Osteopontin</protein> , a component of extracellular matrix , is synthesized by <cell_type>macrophages</cell_type> in atherosclerotic plaques ."}
{"id": "1833", "text": "In this study , we examined whether PPARgamma ligand regulates osteopontin gene expression in THP-1 cells , a cell line derived from human monocytic leukemia cells which can differentiate to macrophage upon stimulation with phorbol ester PMA .", "annotated_text": "In this study , we examined whether <protein>PPARgamma</protein> ligand regulates osteopontin gene expression in <cell_line>THP-1 cells</cell_line> , a cell line derived from <cell_type>human monocytic leukemia cells</cell_type> which can differentiate to <cell_type>macrophage</cell_type> upon stimulation with phorbol ester PMA ."}
{"id": "1834", "text": "Northern blot analysis showed that osteopontin expression is markedly induced in response to PMA .", "annotated_text": "Northern blot analysis showed that osteopontin expression is markedly induced in response to PMA ."}
{"id": "1835", "text": "Troglitazone , a PPARgamma ligand , dramatically attenuated the PMA-induced osteopontin expression .", "annotated_text": "Troglitazone , a <protein>PPARgamma</protein> ligand , dramatically attenuated the PMA-induced osteopontin expression ."}
{"id": "1836", "text": "Transient transfection assays of the human osteopontin promoter/luciferase construct which contains a 5'-flanking region between -1500 and +87 relative to the transcription start site demonstrate that either treatment with troglitazone or cotransfection of PPARgamma expression vector inhibits osteopontin promoter activity .", "annotated_text": "Transient transfection assays of the <dna>human osteopontin promoter/luciferase construct</dna> which contains a <dna>5'-flanking region</dna> between -1500 and +87 relative to the <dna>transcription start site</dna> demonstrate that either treatment with troglitazone or cotransfection of <dna>PPARgamma expression vector</dna> inhibits osteopontin promoter activity ."}
{"id": "1837", "text": "These data indicate that troglitazone reduces osteopontin gene expression at transcriptional level through PPARgamma activation , and suggest the role of troglitazone in inhibiting the ability of macrophages to produce extracellular matrix , which is particularly relevant to atherosclerotic plaque formation .", "annotated_text": "These data indicate that troglitazone reduces osteopontin gene expression at transcriptional level through <protein>PPARgamma</protein> activation , and suggest the role of troglitazone in inhibiting the ability of <cell_type>macrophages</cell_type> to produce extracellular matrix , which is particularly relevant to atherosclerotic plaque formation ."}
{"id": "1838", "text": "Transcription factor NF-kappa B regulates Ig lambda light chain gene rearrangement .", "annotated_text": "<protein>Transcription factor NF-kappa B</protein> regulates <protein>Ig lambda</protein> light chain gene rearrangement ."}
{"id": "1839", "text": "The tissue- and stage-specific assembly of Ig and TCR genes is mediated by a common V ( D ) J recombinase complex in precursor lymphocytes .", "annotated_text": "The tissue- and stage-specific assembly of <dna>Ig and TCR genes</dna> is mediated by a common <protein>V ( D ) J recombinase complex</protein> in <cell_type>precursor lymphocytes</cell_type> ."}
{"id": "1840", "text": "Directed alterations in the accessibility of V , D , and J gene segments target the recombinase to specific Ag receptor loci .", "annotated_text": "Directed alterations in the accessibility of <dna>V , D , and J gene segments</dna> target the <protein>recombinase</protein> to specific <dna>Ag receptor loci</dna> ."}
{"id": "1841", "text": "Accessibility within a given locus is regulated by the functional interaction of transcription factors with cognate enhancer elements and correlates with the transcriptional activity of unrearranged gene segments .", "annotated_text": "Accessibility within a given <dna>locus</dna> is regulated by the functional interaction of <protein>transcription factors</protein> with <dna>cognate enhancer elements</dna> and correlates with the transcriptional activity of unrearranged <dna>gene segments</dna> ."}
{"id": "1842", "text": "As demonstrated in our prior studies , rearrangement of the Igkappa locus is regulated by the inducible transcription factor NF-kappaB .", "annotated_text": "As demonstrated in our prior studies , rearrangement of the <dna>Igkappa locus</dna> is regulated by the <protein>inducible transcription factor</protein> <protein>NF-kappaB</protein> ."}
{"id": "1843", "text": "In contrast to the Igkappa locus , known transcriptional control elements in the Iglambda locus lack functional NF-kappaB binding sites .", "annotated_text": "In contrast to the <dna>Igkappa locus</dna> , known <dna>transcriptional control elements</dna> in the <dna>Iglambda locus</dna> lack functional <dna>NF-kappaB binding sites</dna> ."}
{"id": "1844", "text": "Consistent with this observation , the expression of assembled Iglambda genes in mature B cells has been shown to be NF-kappaB independent .", "annotated_text": "Consistent with this observation , the expression of assembled <dna>Iglambda genes</dna> in <cell_type>mature B cells</cell_type> has been shown to be <protein>NF-kappaB</protein> independent ."}
{"id": "1845", "text": "Nonetheless , we now show that specific repression of NF-kappaB inhibits germline transcription and recombination of Iglambda gene segments in precursor B cells .", "annotated_text": "Nonetheless , we now show that specific repression of <protein>NF-kappaB</protein> inhibits germline transcription and recombination of <dna>Iglambda gene segments</dna> in <cell_type>precursor B cells</cell_type> ."}
{"id": "1846", "text": "Molecular analyses indicate that the block in NF-kappaB impairs Iglambda rearrangement at the level of recombinase accessibility .", "annotated_text": "Molecular analyses indicate that the block in <protein>NF-kappaB</protein> impairs Iglambda rearrangement at the level of <protein>recombinase</protein> accessibility ."}
{"id": "1847", "text": "In contrast , the activities of known Iglambda promoter and enhancer elements are unaffected in the same cellular background .", "annotated_text": "In contrast , the activities of known <dna>Iglambda promoter</dna> and <dna>enhancer elements</dna> are unaffected in the same cellular background ."}
{"id": "1848", "text": "These findings expand the range of NF-kappaB action in precursor B cells beyond Igkappa to include the control of recombinational accessibility at both L chain loci .", "annotated_text": "These findings expand the range of <protein>NF-kappaB</protein> action in <cell_type>precursor B cells</cell_type> beyond <protein>Igkappa</protein> to include the control of recombinational accessibility at both <dna>L chain loci</dna> ."}
{"id": "1849", "text": "Moreover , our results strongly suggest the existence of a novel Iglambda regulatory element that is either directly or indirectly activated by NF-kappaB during the early stages of B cell development .", "annotated_text": "Moreover , our results strongly suggest the existence of a novel <dna>Iglambda regulatory element</dna> that is either directly or indirectly activated by <protein>NF-kappaB</protein> during the early stages of B cell development ."}
{"id": "1850", "text": "Transcription factor STAT5A is a substrate of Bruton 's tyrosine kinase in B cells .", "annotated_text": "<protein>Transcription factor</protein> <protein>STAT5A</protein> is a substrate of <protein>Bruton 's tyrosine kinase</protein> in <cell_type>B cells</cell_type> ."}
{"id": "1851", "text": "STAT5A is a molecular regulator of proliferation , differentiation , and apoptosis in lymphohematopoietic cells .", "annotated_text": "<protein>STAT5A</protein> is a molecular regulator of proliferation , differentiation , and apoptosis in <cell_type>lymphohematopoietic cells</cell_type> ."}
{"id": "1852", "text": "Here we show that STAT5A can serve as a functional substrate of Bruton 's tyrosine kinase ( BTK ) .", "annotated_text": "Here we show that <protein>STAT5A</protein> can serve as a functional substrate of <protein>Bruton 's tyrosine kinase</protein> ( <protein>BTK</protein> ) ."}
{"id": "1853", "text": "Purified recombinant BTK was capable of directly binding purified recombinant STAT5A with high affinity ( K ( d ) = 44 nm ) , as determined by surface plasmon resonance using a BIAcore biosensor system .", "annotated_text": "<protein>Purified recombinant BTK</protein> was capable of directly binding <protein>purified recombinant STAT5A</protein> with high affinity ( K ( d ) = 44 nm ) , as determined by surface plasmon resonance using a BIAcore biosensor system ."}
{"id": "1854", "text": "BTK was also capable of tyrosine-phosphorylating ectopically expressed recombinant STAT5A on Tyr ( 694 ) both in vitro and in vivo in a Janus kinase 3 -independent fashion .", "annotated_text": "<protein>BTK</protein> was also capable of tyrosine-phosphorylating ectopically expressed <protein>recombinant STAT5A</protein> on Tyr ( 694 ) both in vitro and in vivo in a <protein>Janus kinase 3</protein> -independent fashion ."}
{"id": "1855", "text": "BTK phosphorylated the Y665F , Y668F , and Y682F , Y683F mutants but not the Y694F mutant of STAT5A .", "annotated_text": "<protein>BTK</protein> phosphorylated the <protein>Y665F , Y668F , and Y682F , Y683F mutants</protein> but not the <protein>Y694F mutant</protein> of <protein>STAT5A</protein> ."}
{"id": "1856", "text": "STAT5A mutations in the Src homology 2 ( SH2 ) and SH3 domains did not alter the BTK -mediated tyrosine phosphorylation .", "annotated_text": "STAT5A mutations in the <protein>Src homology 2 ( SH2 ) and SH3 domains</protein> did not alter the <protein>BTK</protein> -mediated tyrosine phosphorylation ."}
{"id": "1857", "text": "Recombinant BTK proteins with mutant pleckstrin homology , SH2 , or SH3 domains were capable of phosphorylating STAT5A , whereas recombinant BTK proteins with SH1/kinase domain mutations were not .", "annotated_text": "<protein>Recombinant BTK proteins</protein> with mutant pleckstrin homology , <protein>SH2 , or SH3 domains</protein> were capable of phosphorylating <protein>STAT5A</protein> , whereas <protein>recombinant BTK proteins</protein> with SH1/kinase domain mutations were not ."}
{"id": "1858", "text": "In pull-down experiments , only full-length BTK and its SH1/kinase domain ( but not the pleckstrin homology , SH2 , or SH3 domains ) were capable of binding STAT5A .", "annotated_text": "In pull-down experiments , only <protein>full-length BTK</protein> and its <protein>SH1/kinase domain</protein> ( but not the pleckstrin homology , <protein>SH2 , or SH3 domains</protein> ) were capable of binding <protein>STAT5A</protein> ."}
{"id": "1859", "text": "Ectopically expressed BTK kinase domain was capable of tyrosine-phosphorylating STAT5A both in vitro and in vivo .", "annotated_text": "Ectopically expressed <protein>BTK kinase domain</protein> was capable of tyrosine-phosphorylating <protein>STAT5A</protein> both in vitro and in vivo ."}
{"id": "1860", "text": "BTK -mediated tyrosine phosphorylation of ectopically expressed wild type ( but not Tyr ( 694 ) mutant ) STAT5A enhanced its DNA binding activity .", "annotated_text": "<protein>BTK</protein> -mediated tyrosine phosphorylation of ectopically expressed wild type ( but not <protein>Tyr ( 694 ) mutant</protein> ) <protein>STAT5A</protein> enhanced its DNA binding activity ."}
{"id": "1861", "text": "In BTK -competent chicken B cells , anti-IgM-stimulated tyrosine phosphorylation of STAT5 protein was prevented by pretreatment with the BTK inhibitor LFM-A13 but not by pretreatment with the JAK3 inhibitor HI-P131 .", "annotated_text": "In <protein>BTK</protein> -competent chicken <cell_type>B cells</cell_type> , anti-IgM-stimulated tyrosine phosphorylation of <protein>STAT5 protein</protein> was prevented by pretreatment with the <protein>BTK</protein> inhibitor LFM-A13 but not by pretreatment with the JAK3 inhibitor HI-P131 ."}
{"id": "1862", "text": "B cell antigen receptor ligation resulted in enhanced tyrosine phosphorylation of STAT5 in BTK -deficient chicken B cells reconstituted with wild type human BTK but not in BTK -deficient chicken B cells reconstituted with kinase-inactive mutant BTK .", "annotated_text": "B cell antigen receptor ligation resulted in enhanced tyrosine phosphorylation of <protein>STAT5</protein> in <protein>BTK</protein> -deficient chicken <cell_type>B cells</cell_type> reconstituted with <protein>wild type human BTK</protein> but not in <protein>BTK</protein> -deficient chicken <cell_type>B cells</cell_type> reconstituted with <protein>kinase-inactive mutant BTK</protein> ."}
{"id": "1863", "text": "Similarly , anti-IgM stimulation resulted in enhanced tyrosine phosphorylation of STAT5A in BTK -competent B cells from wild type mice but not in BTK -deficient B cells from XID mice .", "annotated_text": "Similarly , anti-IgM stimulation resulted in enhanced tyrosine phosphorylation of <protein>STAT5A</protein> in <protein>BTK</protein> -competent <cell_type>B cells</cell_type> from wild type mice but not in <protein>BTK</protein> -deficient <cell_type>B cells</cell_type> from XID mice ."}
{"id": "1864", "text": "In contrast to B cells from XID mice , B cells from JAK3 knockout mice showed a normal STAT5A phosphorylation response to anti-IgM stimulation .", "annotated_text": "In contrast to <cell_type>B cells</cell_type> from XID mice , <cell_type>B cells</cell_type> from JAK3 knockout mice showed a normal STAT5A phosphorylation response to anti-IgM stimulation ."}
{"id": "1865", "text": "These findings provide unprecedented experimental evidence that BTK plays a nonredundant and pivotal role in B cell antigen receptor-mediated STAT5A activation in B cells", "annotated_text": "These findings provide unprecedented experimental evidence that <protein>BTK</protein> plays a nonredundant and pivotal role in B cell antigen receptor-mediated STAT5A activation in <cell_type>B cells</cell_type>"}
{"id": "1866", "text": "Role of T-bet in commitment of TH1 cells before IL-12 -dependent selection .", "annotated_text": "Role of <protein>T-bet</protein> in commitment of <cell_type>TH1 cells</cell_type> before <protein>IL-12</protein> -dependent selection ."}
{"id": "1867", "text": "How cytokines control differentiation of helper T ( TH ) cells is controversial .", "annotated_text": "How <protein>cytokines</protein> control differentiation of <cell_type>helper T ( TH ) cells</cell_type> is controversial ."}
{"id": "1868", "text": "We show that T-bet , without apparent assistance from interleukin 12 ( IL-12 ) / STAT4 , specifies TH1 effector fate by targeting chromatin remodeling to individual interferon-gamma ( IFN-gamma ) alleles and by inducing IL-12 receptor beta2 expression .", "annotated_text": "We show that <protein>T-bet</protein> , without apparent assistance from <protein>interleukin 12 ( IL-12 )</protein> / <protein>STAT4</protein> , specifies <cell_type>TH1</cell_type> effector fate by targeting chromatin remodeling to individual <dna>interferon-gamma ( IFN-gamma ) alleles</dna> and by inducing <dna>IL-12 receptor beta2</dna> expression ."}
{"id": "1869", "text": "Subsequently , it appears that IL-12 / STAT4 serves two essential functions in the development of TH1 cells : as growth signal , inducing survival and cell division ; and as trans-activator , prolonging IFN-gamma synthesis through a genetic interaction with the coactivator , CREB-binding protein .", "annotated_text": "Subsequently , it appears that <protein>IL-12</protein> / <protein>STAT4</protein> serves two essential functions in the development of <cell_type>TH1 cells</cell_type> : as <protein>growth signal</protein> , inducing survival and cell division ; and as <protein>trans-activator</protein> , prolonging <protein>IFN-gamma</protein> synthesis through a genetic interaction with the <protein>coactivator</protein> , <protein>CREB-binding protein</protein> ."}
{"id": "1870", "text": "These results suggest that a cytokine does not simply induce TH fate choice but instead may act as an essential secondary stimulus that mediates selective survival of a lineage .", "annotated_text": "These results suggest that a <protein>cytokine</protein> does not simply induce TH fate choice but instead may act as an essential secondary stimulus that mediates selective survival of a lineage ."}
{"id": "1871", "text": "Stat6 is necessary and sufficient for IL-4 's role in Th2 differentiation and cell expansion .", "annotated_text": "<protein>Stat6</protein> is necessary and sufficient for IL-4 's role in Th2 differentiation and cell expansion ."}
{"id": "1872", "text": "IL-4 plays a critical role in the differentiation of T CR-stimulated naive CD4 T cells to the Th2 phenotype .", "annotated_text": "<protein>IL-4</protein> plays a critical role in the differentiation of T <cell_type>CR-stimulated naive CD4 T cells</cell_type> to the Th2 phenotype ."}
{"id": "1873", "text": "In response to IL-4 , the IL-4R activates a set of phosphotyrosine binding domain-containing proteins , including insulin receptor substrate 1/2 , Shc , and IL-4R interacting protein , as well as Stat6 .", "annotated_text": "In response to <protein>IL-4</protein> , the <protein>IL-4R</protein> activates a set of <protein>phosphotyrosine binding domain-containing proteins</protein> , including <protein>insulin receptor substrate 1/2</protein> , <protein>Shc</protein> , and <protein>IL-4R interacting protein</protein> , as well as <protein>Stat6</protein> ."}
{"id": "1874", "text": "Stat6 has been shown to be required for Th2 differentiation .", "annotated_text": "<protein>Stat6</protein> has been shown to be required for Th2 differentiation ."}
{"id": "1875", "text": "To determine the roles of the phosphotyrosine binding adaptors in Th2 differentiation , we prepared a retrovirus containing a mutant of the human ( h ) IL-4R alpha-chain , Y497F , which is unable to recruit these adaptors .", "annotated_text": "To determine the roles of the <protein>phosphotyrosine binding adaptors</protein> in Th2 differentiation , we prepared a retrovirus containing a mutant of the <protein>human ( h ) IL-4R alpha-chain</protein> , <protein>Y497F</protein> , which is unable to recruit these adaptors ."}
{"id": "1876", "text": "The mutant hIL-4Ralpha , as well as the wild-type ( WT ) hIL-4Ralpha , was introduced into naive CD4 T cells .", "annotated_text": "The <protein>mutant hIL-4Ralpha</protein> , as well as the <protein>wild-type ( WT ) hIL-4Ralpha</protein> , was introduced into <cell_type>naive CD4 T cells</cell_type> ."}
{"id": "1877", "text": "Upon hIL-4 stimulation , Y497F worked as well as the WT hIL-4Ralpha in driving Th2 differentiation , as measured by Gata3 up-regulation and IL-4 production .", "annotated_text": "Upon hIL-4 stimulation , <protein>Y497F</protein> worked as well as the <protein>WT hIL-4Ralpha</protein> in driving Th2 differentiation , as measured by Gata3 up-regulation and IL-4 production ."}
{"id": "1878", "text": "Furthermore , IL-4-driven cell expansion was also normal in the cells infected with Y497F , although cells infected with Y497F were not capable of phosphorylating insulin receptor substrate 2 .", "annotated_text": "Furthermore , IL-4-driven cell expansion was also normal in the cells infected with <protein>Y497F</protein> , although cells infected with <protein>Y497F</protein> were not capable of phosphorylating <protein>insulin receptor substrate 2</protein> ."}
{"id": "1879", "text": "These results suggest that the signal pathway mediated by Y497 is dispensable for both IL-4 -driven Th2 differentiation and cell expansion .", "annotated_text": "These results suggest that the signal pathway mediated by <protein>Y497</protein> is dispensable for both <protein>IL-4</protein> -driven Th2 differentiation and cell expansion ."}
{"id": "1880", "text": "Both WT and Y497F hIL-4Ralpha lose the ability to drive Th2 differentiation and cell expansion in Stat6-knockout CD4 T cells .", "annotated_text": "Both <protein>WT and Y497F hIL-4Ralpha</protein> lose the ability to drive Th2 differentiation and cell expansion in <cell_type>Stat6-knockout CD4 T cells</cell_type> ."}
{"id": "1881", "text": "A constitutively activated form of Stat6 introduced into CD4 T cells resulted in both Th2 differentiation and enhanced cell expansion .", "annotated_text": "A constitutively activated form of <protein>Stat6</protein> introduced into <cell_type>CD4 T cells</cell_type> resulted in both Th2 differentiation and enhanced cell expansion ."}
{"id": "1882", "text": "Thus , activated Stat6 is necessary and sufficient to mediate both IL-4 -driven Th2 differentiation and cell expansion in CD4 T cells .", "annotated_text": "Thus , <protein>activated Stat6</protein> is necessary and sufficient to mediate both <protein>IL-4</protein> -driven Th2 differentiation and cell expansion in <cell_type>CD4 T cells</cell_type> ."}
{"id": "1883", "text": "The effect of HIV-1 regulatory proteins on cellular genes : derepression of the IL-2 promoter by Tat .", "annotated_text": "The effect of <protein>HIV-1 regulatory proteins</protein> on cellular genes : derepression of the <dna>IL-2 promoter</dna> by <protein>Tat</protein> ."}
{"id": "1884", "text": "In HIV-infected individuals dysregulation of the immune system is characterized by severe disorders of the cytokine network .", "annotated_text": "In HIV-infected individuals dysregulation of the immune system is characterized by severe disorders of the cytokine network ."}
{"id": "1885", "text": "Increase secretion of IL-2 , the major T cell growth and differentiation cytokine , may play a decisive role in sensitization of T cells for activation induced apoptosis and indirect death of activated T cells through augmented virus replication .", "annotated_text": "Increase secretion of <protein>IL-2</protein> , the major <cell_type>T cell</cell_type> growth and differentiation <protein>cytokine</protein> , may play a decisive role in sensitization of <cell_type>T cells</cell_type> for activation induced apoptosis and indirect death of <cell_type>activated T cells</cell_type> through augmented virus replication ."}
{"id": "1886", "text": "We investigated the cause of enhanced IL-2 secretion and found that the HIV Tat induces this effect .", "annotated_text": "We investigated the cause of enhanced IL-2 secretion and found that the <protein>HIV Tat</protein> induces this effect ."}
{"id": "1887", "text": "We demonstrate that increased IL-2 secretion is due to Tat -enhanced IL-2 promoter activation .", "annotated_text": "We demonstrate that increased IL-2 secretion is due to <protein>Tat</protein> -enhanced <dna>IL-2 promoter</dna> activation ."}
{"id": "1888", "text": "Tat derepresses and activates the distal AP-1 site ( position -185 to -177 ) in the IL-2 promoter .", "annotated_text": "<protein>Tat</protein> derepresses and activates the <dna>distal AP-1 site</dna> ( <dna>position -185 to -177</dna> ) in the <dna>IL-2 promoter</dna> ."}
{"id": "1889", "text": "In nonstimulated T cells a repressor complex containing NF-IL6 , JunB , c-Fos and Fra-1 is formed on the AP-1 ( IL-2/d ) site and represses IL-2 promoter activity .", "annotated_text": "In <cell_type>nonstimulated T cells</cell_type> a repressor complex containing <protein>NF-IL6</protein> , <protein>JunB</protein> , <protein>c-Fos</protein> and <protein>Fra-1</protein> is formed on the <dna>AP-1 ( IL-2/d ) site</dna> and represses <dna>IL-2 promoter</dna> activity ."}
{"id": "1890", "text": "After T cell activation , a heterodimeric activator containing p65 and c-Jun binds to the AP-1 ( IL-2/d ) site .", "annotated_text": "After T cell activation , a <protein>heterodimeric activator</protein> containing <protein>p65</protein> and <protein>c-Jun</protein> binds to the <dna>AP-1 ( IL-2/d ) site</dna> ."}
{"id": "1891", "text": "HIV Tat enhances activation of NF-kappaB and consequently , activates the AP-1 ( IL-2/d ) site .", "annotated_text": "<protein>HIV Tat</protein> enhances activation of <protein>NF-kappaB</protein> and consequently , activates the <dna>AP-1 ( IL-2/d ) site</dna> ."}
{"id": "1892", "text": "Our data provide evidence for a novel mechanism by which HIV Tat dysregulates IL-2 production and therefore may contribute to the HIV-1 infection in a way yet to be clarified .", "annotated_text": "Our data provide evidence for a novel mechanism by which <protein>HIV Tat</protein> dysregulates IL-2 production and therefore may contribute to the HIV-1 infection in a way yet to be clarified ."}
{"id": "1893", "text": "Transforming growth factor-beta1 interferes with thrombopoietin-induced signal transduction in megakaryoblastic and erythroleukemic cells .", "annotated_text": "<protein>Transforming growth factor-beta1</protein> interferes with thrombopoietin-induced signal transduction in <cell_type>megakaryoblastic and erythroleukemic cells</cell_type> ."}
{"id": "1894", "text": "OBJECTIVE : Thrombopoietin ( TPO ) and transforming growth factor-beta ( 1 ) ( TGF-beta ( 1 ) ) have been shown to exert opposite effects on proliferation and megakaryocytic differentiation of hematopoietic cells .", "annotated_text": "OBJECTIVE : <protein>Thrombopoietin</protein> ( <protein>TPO</protein> ) and <protein>transforming growth factor-beta ( 1 )</protein> ( <protein>TGF-beta ( 1 )</protein> ) have been shown to exert opposite effects on proliferation and megakaryocytic differentiation of <cell_type>hematopoietic cells</cell_type> ."}
{"id": "1895", "text": "To determine whether TGF-beta ( 1 ) interferes directly with TPO -induced signal transduction in hematopoietic cells , we compared the regulatory effects in the TPO -responsive cell lines Mo-7e and HEL .", "annotated_text": "To determine whether <protein>TGF-beta ( 1 )</protein> interferes directly with <protein>TPO</protein> -induced signal transduction in <cell_type>hematopoietic cells</cell_type> , we compared the regulatory effects in the <protein>TPO</protein> -responsive cell lines Mo-7e and HEL ."}
{"id": "1896", "text": "MATERIALS AND METHODS : The cells were stimulated by 100 ng/mL TPO and/or 100 ng/mL TGF-beta1 and analyzed for proliferation ( 3H thymidine incorporation ) , viability ( trypan blue exclusion ) , and protein expression and phosphorylation ( Western blot ) .", "annotated_text": "MATERIALS AND METHODS : The cells were stimulated by 100 ng/mL <protein>TPO</protein> and/or 100 ng/mL <protein>TGF-beta1</protein> and analyzed for proliferation ( 3H thymidine incorporation ) , viability ( trypan blue exclusion ) , and protein expression and phosphorylation ( Western blot ) ."}
{"id": "1897", "text": "RESULTS : TPO enhanced the proliferation of Mo-7e cells as determined by 3H-thymidine incorporation , whereas TGF-beta1 suppressed baseline cell growth and antagonized the proliferative effect of TPO .", "annotated_text": "RESULTS : <protein>TPO</protein> enhanced the proliferation of <cell_line>Mo-7e cells</cell_line> as determined by 3H-thymidine incorporation , whereas <protein>TGF-beta1</protein> suppressed baseline cell growth and antagonized the proliferative effect of <protein>TPO</protein> ."}
{"id": "1898", "text": "TPO -induced proliferation also was reduced by a specific inhibitor of the mitogen-activated protein kinase ( MAPK ) pathway ( PD098059 ) , which inhibits activation of the MAPK extracellular signal-regulated kinases ( ERK ) ERK1 and ERK2 , and AG490 , an inhibitor of Janus kinase-2 , which completely blocked TPO -induced proliferation .", "annotated_text": "<protein>TPO</protein> -induced proliferation also was reduced by a specific inhibitor of the <protein>mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) pathway ( PD098059 ) , which inhibits activation of the <protein>MAPK extracellular signal-regulated kinases</protein> ( <protein>ERK</protein> ) <protein>ERK1</protein> and <protein>ERK2</protein> , and AG490 , an inhibitor of <protein>Janus kinase-2</protein> , which completely blocked <protein>TPO</protein> -induced proliferation ."}
{"id": "1899", "text": "As demonstrated by Western blotting , TGF-beta1 reduced the TPO -stimulated ERK1 / ERK2 and STAT5 phosphorylation in Mo-7e and HEL cells .", "annotated_text": "As demonstrated by Western blotting , <protein>TGF-beta1</protein> reduced the <protein>TPO</protein> -stimulated <protein>ERK1</protein> / <protein>ERK2</protein> and STAT5 phosphorylation in <cell_line>Mo-7e and HEL cells</cell_line> ."}
{"id": "1900", "text": "This effect was completely reversed by preincubation with a tyrosine phosphatase inhibitor ( Na3VO4 ) , which suggests that TGF-beta1 activated a phosphatase .", "annotated_text": "This effect was completely reversed by preincubation with a tyrosine phosphatase inhibitor ( Na3VO4 ) , which suggests that <protein>TGF-beta1</protein> activated a <protein>phosphatase</protein> ."}
{"id": "1901", "text": "Although STAT3 also was activated by TPO , STAT3 activation remained unaltered by TGF-beta1 .", "annotated_text": "Although <protein>STAT3</protein> also was activated by <protein>TPO</protein> , <protein>STAT3</protein> activation remained unaltered by <protein>TGF-beta1</protein> ."}
{"id": "1902", "text": "CONCLUSION : Taken together , these data suggest that TGF-beta1 modulates TPO -mediated effects on megakaryocytic proliferation by interfering with TPO -induced signal transduction , particularly by reducing the activities of MAPK ERK1/ERK2 and STAT5 .", "annotated_text": "CONCLUSION : Taken together , these data suggest that <protein>TGF-beta1</protein> modulates <protein>TPO</protein> -mediated effects on megakaryocytic proliferation by interfering with <protein>TPO</protein> -induced signal transduction , particularly by reducing the activities of <protein>MAPK ERK1/ERK2 and STAT5</protein> ."}
{"id": "1903", "text": "Invariant chain induces B cell maturation by activating a TAF ( II ) 105-NF-kappaB -dependent transcription program .", "annotated_text": "<protein>Invariant chain</protein> induces B cell maturation by activating a <protein>TAF ( II ) 105-NF-kappaB</protein> -dependent transcription program ."}
{"id": "1904", "text": "Early stages of B cell development occur in the bone marrow , resulting in formation of immature B cells .", "annotated_text": "Early stages of B cell development occur in the bone marrow , resulting in formation of <cell_type>immature B cells</cell_type> ."}
{"id": "1905", "text": "From there these immature cells migrate to the spleen where they differentiate to mature cells .", "annotated_text": "From there these <cell_type>immature cells</cell_type> migrate to the spleen where they differentiate to <cell_type>mature cells</cell_type> ."}
{"id": "1906", "text": "This final maturation step is crucial for the B cells to become responsive to antigens and to participate in the immune response .", "annotated_text": "This final maturation step is crucial for the <cell_type>B cells</cell_type> to become responsive to <protein>antigens</protein> and to participate in the immune response ."}
{"id": "1907", "text": "Recently , invariant chain ( Ii ) , a major histocompatibility complex class II chaperone , as well as the transcription factors c-Rel and p65/RelA , were found to play a role in the final antigen-independent differentiation stage of B cells in the spleen .", "annotated_text": "Recently , <protein>invariant chain</protein> ( <protein>Ii</protein> ) , a <protein>major histocompatibility complex class II chaperone</protein> , as well as the <protein>transcription factors</protein> <protein>c-Rel</protein> and <protein>p65/RelA</protein> , were found to play a role in the final antigen-independent differentiation stage of <cell_type>B cells</cell_type> in the spleen ."}
{"id": "1908", "text": "In this study , we investigated a possible link between Ii -dependent B cell maturation and the NF-kappaB pathway .", "annotated_text": "In this study , we investigated a possible link between <protein>Ii</protein> -dependent B cell maturation and the NF-kappaB pathway ."}
{"id": "1909", "text": "Our studies indicate that Ii -induced B cell maturation involves activation of transcription mediated by the NF-kappaB p65/RelA homodimer and requires the B cell-enriched coactivator TBP-associated factor ( II ) 105 .", "annotated_text": "Our studies indicate that <protein>Ii</protein> -induced B cell maturation involves activation of transcription mediated by the <protein>NF-kappaB p65/RelA homodimer</protein> and requires the <protein>B cell-enriched coactivator</protein> <protein>TBP-associated factor ( II ) 105</protein> ."}
{"id": "1910", "text": "Androgens indirectly accelerate thymocyte apoptosis .", "annotated_text": "Androgens indirectly accelerate <cell_type>thymocyte</cell_type> apoptosis ."}
{"id": "1911", "text": "Apoptotic processes , or the disturbance of the natural regulation of these processes , may be involved in the pathogenesis of autoimmune diseases ( AID ) .", "annotated_text": "Apoptotic processes , or the disturbance of the natural regulation of these processes , may be involved in the pathogenesis of autoimmune diseases ( AID ) ."}
{"id": "1912", "text": "Women are , in general , more susceptible than men to develop AID like rheumatoid arthritis .", "annotated_text": "Women are , in general , more susceptible than men to develop AID like rheumatoid arthritis ."}
{"id": "1913", "text": "Androgens and glucocorticoids , in contrast to oestrogens , have favourable effects in AID models as well as in human AID .", "annotated_text": "Androgens and glucocorticoids , in contrast to oestrogens , have favourable effects in AID models as well as in human AID ."}
{"id": "1914", "text": "It is known that glucocorticoids ( GC ) , used for treatment of AID , increase apoptosis in the thymus resulting in decreased numbers of CD4+ CD8+ thymocytes .", "annotated_text": "It is known that glucocorticoids ( GC ) , used for treatment of AID , increase apoptosis in the thymus resulting in decreased numbers of <cell_type>CD4+ CD8+ thymocytes</cell_type> ."}
{"id": "1915", "text": "It was asked whether androgens , in contrast to oestrogens , exert their favourable effects in the treatment of AID by a mechanism comparable to that described for GC by eliminating the apoptosis prone CD4+ CD8+ population in the thymus .", "annotated_text": "It was asked whether androgens , in contrast to oestrogens , exert their favourable effects in the treatment of AID by a mechanism comparable to that described for GC by eliminating the apoptosis prone <cell_type>CD4+ CD8+ population</cell_type> in the thymus ."}
{"id": "1916", "text": "Although both androgens and oestrogens proved thymolytic , a significantly decreased percentage of CD4+ CD8+ thymocytes was observed by flow cytometry after treatment of mice with the androgen methyltestosterone , but not with the oestrogen ethinylestradiol .", "annotated_text": "Although both androgens and oestrogens proved thymolytic , a significantly decreased percentage of <cell_type>CD4+ CD8+ thymocytes</cell_type> was observed by flow cytometry after treatment of mice with the androgen methyltestosterone , but not with the oestrogen ethinylestradiol ."}
{"id": "1917", "text": "To investigate whether the observed thymolytic effects were due to the presence of hormone receptors on thymocytes , cells were isolated from the thymus and incubated with androgens or oestrogens to measure apoptosis .", "annotated_text": "To investigate whether the observed thymolytic effects were due to the presence of <protein>hormone receptors</protein> on <cell_type>thymocytes</cell_type> , cells were isolated from the thymus and incubated with androgens or oestrogens to measure apoptosis ."}
{"id": "1918", "text": "Several techniques were used to determine thymocyte apoptosis in vitro , but no enhanced apoptotic signal was observed .", "annotated_text": "Several techniques were used to determine <cell_type>thymocyte</cell_type> apoptosis in vitro , but no enhanced apoptotic signal was observed ."}
{"id": "1919", "text": "Using the very sensitive TUNEL assay , no direct effect of androgens on thymocytes in vitro could be observed .", "annotated_text": "Using the very sensitive TUNEL assay , no direct effect of androgens on <cell_type>thymocytes</cell_type> in vitro could be observed ."}
{"id": "1920", "text": "This is in sharp contrast to the high signal observed with GC .", "annotated_text": "This is in sharp contrast to the high signal observed with GC ."}
{"id": "1921", "text": "Therefore , upon in vivo androgen treatment , other cells containing androgen receptors than thymocytes are probably involved in inducing the increase in thymic apoptosis .", "annotated_text": "Therefore , upon in vivo androgen treatment , other cells containing <protein>androgen receptors</protein> than <cell_type>thymocytes</cell_type> are probably involved in inducing the increase in thymic apoptosis ."}
{"id": "1922", "text": "To study the role of the androgen receptor on thymocyte apoptosis , androgen receptor mutant ( Tfm/Y ) mice were treated with androgens .", "annotated_text": "To study the role of the <protein>androgen receptor</protein> on <cell_type>thymocyte</cell_type> apoptosis , <protein>androgen receptor</protein> mutant ( Tfm/Y ) mice were treated with androgens ."}
{"id": "1923", "text": "No alterations of thymocyte subpopulations were seen , suggesting that changes in the percentage of CD4+ CD8+ thymocytes after administration of androgens depend on the presence of functional androgen receptors .", "annotated_text": "No alterations of <cell_type>thymocyte subpopulations</cell_type> were seen , suggesting that changes in the percentage of <cell_type>CD4+ CD8+ thymocytes</cell_type> after administration of androgens depend on the presence of functional <protein>androgen receptors</protein> ."}
{"id": "1924", "text": "Thus , it is concluded that androgens indirectly accelerate thymocyte apoptosis in vivo .", "annotated_text": "Thus , it is concluded that androgens indirectly accelerate <cell_type>thymocyte</cell_type> apoptosis in vivo ."}
{"id": "1925", "text": "Inhibition of the transcription factors AP-1 and NF-kappaB in CD4 T cells by peroxisome proliferator-activated receptor gamma ligands .", "annotated_text": "Inhibition of the <protein>transcription factors</protein> <protein>AP-1</protein> and <protein>NF-kappaB</protein> in <cell_type>CD4 T cells</cell_type> by <protein>peroxisome proliferator-activated receptor gamma ligands</protein> ."}
{"id": "1926", "text": "The peroxisome proliferator-activated receptor gamma ( PPARgamma ) , a member of the nuclear hormone receptor superfamily , is essential for adipocyte differentiation and glucose homeostasis .", "annotated_text": "The <protein>peroxisome proliferator-activated receptor gamma</protein> ( <protein>PPARgamma</protein> ) , a member of the <protein>nuclear hormone receptor superfamily</protein> , is essential for adipocyte differentiation and glucose homeostasis ."}
{"id": "1927", "text": "PPARgamma has been found recently to regulate macrophage activation in response to mitogens and inflammation .", "annotated_text": "<protein>PPARgamma</protein> has been found recently to regulate macrophage activation in response to <protein>mitogens</protein> and inflammation ."}
{"id": "1928", "text": "Our study shows PPARgamma to be preferentially expressed in the nuclei of resting T cells and to increase upon activation of T cells by either anti-CD3 and anti-CD28 or phorbol myristyl acetate ( PMA ) .", "annotated_text": "Our study shows <protein>PPARgamma</protein> to be preferentially expressed in the nuclei of <cell_type>resting T cells</cell_type> and to increase upon activation of <cell_type>T cells</cell_type> by either <protein>anti-CD3</protein> and <protein>anti-CD28</protein> or phorbol myristyl acetate ( PMA ) ."}
{"id": "1929", "text": "We also found the PPARgamma ligand ciglitizone to attenuate the activation of T cells by inhibiting cytokine gene expression and anti-CD3 and anti-CD28 or PMA-induced proliferative responses .", "annotated_text": "We also found the <protein>PPARgamma ligand</protein> ciglitizone to attenuate the activation of <cell_type>T cells</cell_type> by inhibiting cytokine gene expression and <protein>anti-CD3</protein> and <protein>anti-CD28</protein> or PMA-induced proliferative responses ."}
{"id": "1930", "text": "Inhibition of both the proliferative response and inflammatory cytokine expression in CD4 T cells was correlated with suppression of the activated transcription factors AP1 and NF-kappaB .", "annotated_text": "Inhibition of both the proliferative response and inflammatory cytokine expression in <cell_type>CD4 T cells</cell_type> was correlated with suppression of the activated <protein>transcription factors</protein> <protein>AP1</protein> and <protein>NF-kappaB</protein> ."}
{"id": "1931", "text": "PPARgamma ligands also strongly inhibited SEA-induced Vbeta3 T cell activation in vivo .", "annotated_text": "<protein>PPARgamma ligands</protein> also strongly inhibited SEA-induced Vbeta3 T cell activation in vivo ."}
{"id": "1932", "text": "These results , together with previous findings of the inhibitory effect of PPARgamma ligands on activated macrophages , provide clear evidence for PPARgamma as a negative regulator of the inflammatory activation of both macrophage and T cells .", "annotated_text": "These results , together with previous findings of the inhibitory effect of <protein>PPARgamma ligands</protein> on <cell_type>activated macrophages</cell_type> , provide clear evidence for <protein>PPARgamma</protein> as a <protein>negative regulator</protein> of the inflammatory activation of both <cell_type>macrophage</cell_type> and <cell_type>T cells</cell_type> ."}
{"id": "1933", "text": "PPARgamma may thus be a potential therapeutic target for the treatment of autoimmunity .", "annotated_text": "<protein>PPARgamma</protein> may thus be a potential therapeutic target for the treatment of autoimmunity ."}
{"id": "1934", "text": "A prominent role for activator protein-1 in the transcription of the human 2B4 ( CD244 ) gene in NK cells .", "annotated_text": "A prominent role for <protein>activator protein-1</protein> in the transcription of the <dna>human 2B4 ( CD244 ) gene</dna> in <cell_type>NK cells</cell_type> ."}
{"id": "1935", "text": "The cell surface glycoprotein 2B4 ( CD244 ) of the Ig superfamily is involved in the regulation of NK and T lymphocyte functions .", "annotated_text": "The <protein>cell surface glycoprotein 2B4</protein> ( <protein>CD244</protein> ) of the <protein>Ig superfamily</protein> is involved in the regulation of <cell_type>NK</cell_type> and <cell_type>T lymphocyte</cell_type> functions ."}
{"id": "1936", "text": "We have recently identified CD48 as the high affinity counterreceptor for 2B4 in both mice and humans .", "annotated_text": "We have recently identified <protein>CD48</protein> as the <protein>high affinity counterreceptor</protein> for <protein>2B4</protein> in both mice and humans ."}
{"id": "1937", "text": "The cytoplasmic domain of 2B4 associates with src homology 2 domain-containing protein or signaling lymphocyte activation molecule-associated protein , whose mutation is the underlying genetic defect in the X-linked lymphoproliferative syndrome .", "annotated_text": "The <protein>cytoplasmic domain</protein> of <protein>2B4</protein> associates with <protein>src homology 2 domain-containing protein</protein> or <protein>signaling lymphocyte activation molecule-associated protein</protein> , whose mutation is the underlying genetic defect in the X-linked lymphoproliferative syndrome ."}
{"id": "1938", "text": "In this study , we report the molecular cloning and characterization of the human 2B4 ( h2B4 ) promoter .", "annotated_text": "In this study , we report the molecular cloning and characterization of the <dna>human 2B4 ( h2B4 ) promoter</dna> ."}
{"id": "1939", "text": "Through primer extension analysis , we found that the transcription of the h2B4 gene initiates at multiple start sites .", "annotated_text": "Through primer extension analysis , we found that the transcription of the <dna>h2B4 gene</dna> initiates at multiple start sites ."}
{"id": "1940", "text": "We isolated h2B4 genomic clones and PCR amplified the 5 ' untranslated region containing the promoter elements .", "annotated_text": "We isolated <dna>h2B4 genomic clones</dna> and PCR amplified the <dna>5 ' untranslated region</dna> containing the <dna>promoter elements</dna> ."}
{"id": "1941", "text": "We have identified a functional AP-1 site that lies between ( -106 to -100 ) through transient transfection analysis in YT cells , a human NK cell line .", "annotated_text": "We have identified a functional <dna>AP-1 site</dna> that lies between ( -106 to -100 ) through transient transfection analysis in <cell_line>YT cells</cell_line> , a <cell_line>human NK cell line</cell_line> ."}
{"id": "1942", "text": "EMSAs with Abs specific for various protein factors of the AP-1 family revealed that multiple members of the Jun family are involved in the regulation of the h2B4 gene .", "annotated_text": "EMSAs with <protein>Abs</protein> specific for various <protein>protein factors</protein> of the <protein>AP-1 family</protein> revealed that multiple members of the <protein>Jun family</protein> are involved in the regulation of the <dna>h2B4 gene</dna> ."}
{"id": "1943", "text": "Mutation of the AP-1 site not only abolishes protein/DNA interactions but also promoter activity .", "annotated_text": "Mutation of the <dna>AP-1 site</dna> not only abolishes protein/DNA interactions but also promoter activity ."}
{"id": "1944", "text": "These results demonstrate a significant role for AP-1 in the transcriptional regulation of the h2B4 gene .", "annotated_text": "These results demonstrate a significant role for <protein>AP-1</protein> in the transcriptional regulation of the <dna>h2B4 gene</dna> ."}
{"id": "1945", "text": "Functional correction of FA-C cells with FANCC suppresses the expression of interferon gamma-inducible genes .", "annotated_text": "Functional correction of <cell_type>FA-C cells</cell_type> with <protein>FANCC</protein> suppresses the expression of <dna>interferon gamma-inducible genes</dna> ."}
{"id": "1946", "text": "Because hematopoietic cells derived from Fanconi anemia ( FA ) patients of the C-complementation group ( FA-C ) are hypersensitive to the inhibitory effects of interferon gamma ( IFNgamma ) , the products of certain IFNgamma-inducible genes known to influence hematopoietic cell survival were quantified .", "annotated_text": "Because <cell_type>hematopoietic cells</cell_type> derived from Fanconi anemia ( FA ) patients of the C-complementation group ( FA-C ) are hypersensitive to the inhibitory effects of <protein>interferon gamma</protein> ( <protein>IFNgamma</protein> ) , the products of certain <dna>IFNgamma-inducible genes</dna> known to influence hematopoietic cell survival were quantified ."}
{"id": "1947", "text": "High constitutive expression of the IFNgamma-inducible genes , IFN-stimulated gene factor 3 gamma subunit ( ISGF3gamma ) , IFN regulatory factor-1 ( IRF-1 ) , and the cyclin-dependent kinase inhibitor p21 ( WAF1 ) was found in FANCC mutant B lymphoblasts , low-density bone marrow cells , and murine embryonic fibroblasts .", "annotated_text": "High constitutive expression of the <dna>IFNgamma-inducible genes</dna> , <protein>IFN-stimulated gene factor 3 gamma subunit</protein> ( <protein>ISGF3gamma</protein> ) , <protein>IFN regulatory factor-1</protein> ( <protein>IRF-1</protein> ) , and the <protein>cyclin-dependent kinase inhibitor p21</protein> ( <protein>WAF1</protein> ) was found in <protein>FANCC</protein> mutant <cell_type>B lymphoblasts</cell_type> , <cell_type>low-density bone marrow cells</cell_type> , and <cell_type>murine embryonic fibroblasts</cell_type> ."}
{"id": "1948", "text": "Paradoxically , these cells do not activate signal transducer and activator of transcription ( STAT ) 1 properly .", "annotated_text": "Paradoxically , these cells do not <protein>activate signal transducer and activator of transcription ( STAT ) 1</protein> properly ."}
{"id": "1949", "text": "In an attempt to clarify mechanisms by which FA-C cells overexpress IFNgamma-inducible genes in the face of defective STAT1 phosphorylation , it was reasoned that decreased levels of activated STAT1 might result in reduced expression of a hematopoietic IFNgamma-responsive protein that normally modulates expression of other IFNgamma-responsive genes .", "annotated_text": "In an attempt to clarify mechanisms by which <cell_type>FA-C cells</cell_type> overexpress <dna>IFNgamma-inducible genes</dna> in the face of defective STAT1 phosphorylation , it was reasoned that decreased levels of <protein>activated STAT1</protein> might result in reduced expression of a <protein>hematopoietic IFNgamma-responsive protein</protein> that normally modulates expression of other <dna>IFNgamma-responsive genes</dna> ."}
{"id": "1950", "text": "Levels of the IFNgamma -inducible factor IFN consensus sequence binding protein ( ICSBP ) , a negative trans-acting regulator of some IFNgamma-inducible genes , were quantified .", "annotated_text": "Levels of the <protein>IFNgamma</protein> -inducible factor <protein>IFN consensus sequence binding protein</protein> ( <protein>ICSBP</protein> ) , a <protein>negative trans-acting regulator</protein> of some <dna>IFNgamma-inducible genes</dna> , were quantified ."}
{"id": "1951", "text": "ICSBP levels were reduced in FA-C B lymphoblasts and MEFs .", "annotated_text": "<protein>ICSBP</protein> levels were reduced in <cell_type>FA-C B lymphoblasts</cell_type> and <cell_type>MEFs</cell_type> ."}
{"id": "1952", "text": "However , enforced expression of ICSBP failed to down-regulate IRF-1 , ISGF3gamma , and p21 ( WAF1 ) .", "annotated_text": "However , enforced expression of <protein>ICSBP</protein> failed to down-regulate <protein>IRF-1</protein> , <protein>ISGF3gamma</protein> , and <protein>p21 ( WAF1 )</protein> ."}
{"id": "1953", "text": "Thus , the FANCC protein functions to modulate expression of a family of genes that in normal cells are inducible only by specific environmental cues for apoptosis or mitogenic inhibition , but it does so independently of the classic IFN-STAT1 pathway and is not the direct result of reduced ICSBP expression .", "annotated_text": "Thus , the <protein>FANCC protein</protein> functions to modulate expression of a family of genes that in normal cells are inducible only by specific environmental cues for apoptosis or mitogenic inhibition , but it does so independently of the classic IFN-STAT1 pathway and is not the direct result of reduced <protein>ICSBP</protein> expression ."}
{"id": "1954", "text": "A genetic investigation of E2A function in lymphocyte development .", "annotated_text": "A genetic investigation of E2A function in lymphocyte development ."}
{"id": "1955", "text": "Lymphocytes are derived from hematopoietic stem cells ( HSC ) following a series of regulated differentiation events .", "annotated_text": "<cell_type>Lymphocytes</cell_type> are derived from <cell_type>hematopoietic stem cells</cell_type> ( <cell_type>HSC</cell_type> ) following a series of regulated differentiation events ."}
{"id": "1956", "text": "Multipotent HSCs become committed to the B cell lineage in bone marrow and the T cell lineage in the thymus after receiving appropriate signals from the corresponding microenvironment .", "annotated_text": "<cell_type>Multipotent HSCs</cell_type> become committed to the <cell_line>B cell lineage</cell_line> in bone marrow and the <cell_line>T cell lineage</cell_line> in the thymus after receiving appropriate signals from the corresponding microenvironment ."}
{"id": "1957", "text": "These committed lymphoid cells must then undergo V ( D ) J recombination at the immunoglobulin gene or T cell receptor gene locus resulting in clonal production of functional B or T lymphocytes , respectively .", "annotated_text": "These committed <cell_type>lymphoid cells</cell_type> must then undergo V ( D ) J recombination at the <dna>immunoglobulin gene</dna> or <dna>T cell receptor gene locus</dna> resulting in clonal production of functional <cell_type>B or T lymphocytes</cell_type> , respectively ."}
{"id": "1958", "text": "Lymphocyte commitment and differentiation are accompanied by programmed gene expression or repression events which are driven by lineage and stage specific transcription factors .", "annotated_text": "Lymphocyte commitment and differentiation are accompanied by programmed gene expression or repression events which are driven by <protein>lineage and stage specific transcription factors</protein> ."}
{"id": "1959", "text": "The basic-helix-loop-helix ( bHLH ) transcription factors encoded by the E2A gene are involved in several differentiation events during B and T cell development , including lineage commitment , initiation of V ( D ) J recombination , and antigen receptor mediated proliferation and differentiation .", "annotated_text": "The <protein>basic-helix-loop-helix ( bHLH ) transcription factors</protein> encoded by the <dna>E2A gene</dna> are involved in several differentiation events during B and T cell development , including lineage commitment , initiation of V ( D ) J recombination , and antigen receptor mediated proliferation and differentiation ."}
{"id": "1960", "text": "Several recent reviews have provided a comprehensive discussion of biochemical , cellular , and genetic research on E2A function in lymphocyte development ( 1 , 2 ) .", "annotated_text": "Several recent reviews have provided a comprehensive discussion of biochemical , cellular , and genetic research on E2A function in lymphocyte development ( 1 , 2 ) ."}
{"id": "1961", "text": "Here , we only discuss some of the genetic approaches our laboratory ( except where it is noted ) has undertaken to investigate the molecular pathways mediated by E2A transcription factors in lymphocyte development", "annotated_text": "Here , we only discuss some of the genetic approaches our laboratory ( except where it is noted ) has undertaken to investigate the molecular pathways mediated by <protein>E2A transcription factors</protein> in lymphocyte development"}
{"id": "1962", "text": "D609 inhibits ionizing radiation-induced oxidative damage by acting as a potent antioxidant .", "annotated_text": "D609 inhibits ionizing radiation-induced oxidative damage by acting as a potent antioxidant ."}
{"id": "1963", "text": "Tricyclodecan-9-yl-xanthogenate ( D609 ) has been extensively studied in biological systems and exhibits a variety of biological functions , including antiviral , antitumor , and anti-inflammatory activities .", "annotated_text": "Tricyclodecan-9-yl-xanthogenate ( D609 ) has been extensively studied in biological systems and exhibits a variety of biological functions , including antiviral , antitumor , and anti-inflammatory activities ."}
{"id": "1964", "text": "Most of these activities have been largely attributed to the inhibitory effect of D609 on phosphatidylcholine-specific phospholipase C .", "annotated_text": "Most of these activities have been largely attributed to the inhibitory effect of D609 on phosphatidylcholine-specific <protein>phospholipase C</protein> ."}
{"id": "1965", "text": "However , as a xanthate derivative , D609 is a strong electrolyte and readily dissociates to xanthate anions and cations of alkali metals in solution .", "annotated_text": "However , as a xanthate derivative , D609 is a strong electrolyte and readily dissociates to xanthate anions and cations of alkali metals in solution ."}
{"id": "1966", "text": "Xanthate anions and protonated xanthic acid contain a free thiol moiety and are highly reductive .", "annotated_text": "Xanthate anions and protonated xanthic acid contain a free thiol moiety and are highly reductive ."}
{"id": "1967", "text": "This implies that D609 and other xanthate derivatives may function as potent antioxidants .", "annotated_text": "This implies that D609 and other xanthate derivatives may function as potent antioxidants ."}
{"id": "1968", "text": "Indeed , we found that D609 inhibited the Fenton reaction-induced oxidation of dihydrorhodamine 123 in a dose-dependent manner similar to that of pyrrolidinedithiocarbamate , a well known antioxidant .", "annotated_text": "Indeed , we found that D609 inhibited the Fenton reaction-induced oxidation of dihydrorhodamine 123 in a dose-dependent manner similar to that of pyrrolidinedithiocarbamate , a well known antioxidant ."}
{"id": "1969", "text": "In addition , D609 inhibited the formation of the alpha-phenyl-tert-butylnitrone-free radical spin adducts and lipid peroxidation of synaptosomal membranes by the Fenton reagents .", "annotated_text": "In addition , D609 inhibited the formation of the alpha-phenyl-tert-butylnitrone-free radical spin adducts and lipid peroxidation of synaptosomal membranes by the Fenton reagents ."}
{"id": "1970", "text": "Furthermore , preincubation of lymphocytes with D609 resulted in a significant diminution of ionizing radiation ( IR ) -induced 1 ) production of reactive oxygen species ; 2 ) decrease in intracellular reduced glutathione ; 3 ) oxidative damage to proteins and lipids ; and 4 ) activation of nuclear factor-kappaB .", "annotated_text": "Furthermore , preincubation of <cell_type>lymphocytes</cell_type> with D609 resulted in a significant diminution of ionizing radiation ( IR ) -induced 1 ) production of reactive oxygen species ; 2 ) decrease in intracellular reduced glutathione ; 3 ) oxidative damage to proteins and lipids ; and 4 ) activation of <protein>nuclear factor-kappaB</protein> ."}
{"id": "1971", "text": "Moreover , when D609 ( 50 mg/kg i.v. ) was administered to mice 10 min prior to total body IR ( 6.5 and 8.5 Gy ) , it protected the mice from IR-induced lethality .", "annotated_text": "Moreover , when D609 ( 50 mg/kg i.v. ) was administered to mice 10 min prior to total body IR ( 6.5 and 8.5 Gy ) , it protected the mice from IR-induced lethality ."}
{"id": "1972", "text": "Thus , these results indicate that D609 is a potent antioxidant and has the ability to inhibit IR-induced cellular oxidative stress .", "annotated_text": "Thus , these results indicate that D609 is a potent antioxidant and has the ability to inhibit IR-induced cellular oxidative stress ."}
{"id": "1973", "text": "Inhibition of AP-1 by the glucocorticoid-inducible protein GILZ .", "annotated_text": "Inhibition of <protein>AP-1</protein> by the glucocorticoid-inducible <protein>protein GILZ</protein> ."}
{"id": "1974", "text": "The immunosuppressive effects of glucocorticoids arise largely by inhibition of cytokine gene expression , which has been ascribed to interference between the glucocorticoid receptor and transcription factors such as AP-1 and NF-kappa B as well as by competition for common coactivators .", "annotated_text": "The immunosuppressive effects of glucocorticoids arise largely by inhibition of cytokine gene expression , which has been ascribed to interference between the <protein>glucocorticoid receptor</protein> and <protein>transcription factors</protein> such as <protein>AP-1</protein> and <protein>NF-kappa B</protein> as well as by competition for common coactivators ."}
{"id": "1975", "text": "Here we show that glucocorticoid-induced inhibition of interleukin-2 mRNA expression in activated normal T cells required new protein synthesis , suggesting that this phenomenon is secondary to expression of glucocorticoid-regulated genes .", "annotated_text": "Here we show that glucocorticoid-induced inhibition of interleukin-2 mRNA expression in <cell_type>activated normal T cells</cell_type> required new protein synthesis , suggesting that this phenomenon is secondary to expression of glucocorticoid-regulated <dna>genes</dna> ."}
{"id": "1976", "text": "One of the most prominent glucocorticoid-induced genes is glucocorticoid-induced leucine zipper ( GILZ ) , which has been reported to inhibit activation-induced up-regulation of Fas ligand ( FasL ) mRNA .", "annotated_text": "One of the most prominent glucocorticoid-induced <dna>genes</dna> is <dna>glucocorticoid-induced leucine zipper</dna> ( <dna>GILZ</dna> ) , which has been reported to inhibit activation-induced up-regulation of <rna>Fas ligand ( FasL ) mRNA</rna> ."}
{"id": "1977", "text": "Indeed , transient expression of GILZ in Jurkat T cells blocked induction of a reporter construct driven by the FasL promoter .", "annotated_text": "Indeed , transient expression of <dna>GILZ</dna> in <cell_line>Jurkat T cells</cell_line> blocked induction of a <dna>reporter construct</dna> driven by the <dna>FasL promoter</dna> ."}
{"id": "1978", "text": "This could be accounted for by GILZ -mediated inhibition of Egr-2 and Egr-3 , NFAT/AP-1 -inducible transcription factors that bind a regulatory element in the FasL promoter and up-regulate FasL expression .", "annotated_text": "This could be accounted for by <protein>GILZ</protein> -mediated inhibition of <protein>Egr-2</protein> and <protein>Egr-3</protein> , <protein>NFAT/AP-1</protein> -inducible <protein>transcription factors</protein> that bind a <dna>regulatory element</dna> in the <dna>FasL promoter</dna> and up-regulate FasL expression ."}
{"id": "1979", "text": "GILZ also potently inhibited AP-1-driven and IL-2 promoter-driven reporter constructs , and recombinant GILZ specifically interacted with c-Fos and c-Jun in vitro and inhibited the binding of active AP-1 to its target DNA .", "annotated_text": "<protein>GILZ</protein> also potently inhibited <dna>AP-1-driven and IL-2 promoter-driven reporter constructs</dna> , and recombinant <protein>GILZ</protein> specifically interacted with <protein>c-Fos</protein> and <protein>c-Jun</protein> in vitro and inhibited the binding of <protein>active AP-1</protein> to its target DNA ."}
{"id": "1980", "text": "Whereas homodimerization of GILZ required the presence of its leucine zipper , the interaction with c-Fos and c-Jun occurred through the N-terminal 60-amino acid region of GILZ .", "annotated_text": "Whereas homodimerization of <protein>GILZ</protein> required the presence of its <protein>leucine zipper</protein> , the interaction with <protein>c-Fos</protein> and <protein>c-Jun</protein> occurred through the <protein>N-terminal</protein> <protein>60-amino acid region</protein> of <protein>GILZ</protein> ."}
{"id": "1981", "text": "Thus , GILZ represents a glucocorticoid-induced gene product that can inhibit a variety of activation-induced events , at least in part by direct interference with AP-1 , and is therefore a candidate for a mediator of glucocorticoid-induced immunosuppression .", "annotated_text": "Thus , <protein>GILZ</protein> represents a glucocorticoid-induced gene product that can inhibit a variety of activation-induced events , at least in part by direct interference with <protein>AP-1</protein> , and is therefore a candidate for a mediator of glucocorticoid-induced immunosuppression ."}
{"id": "1982", "text": "Pharmacokinetic differences between a T cell-tolerizing and a T cell-activating peptide .", "annotated_text": "Pharmacokinetic differences between a T cell-tolerizing and a T cell-activating peptide ."}
{"id": "1983", "text": "Vaccination with a peptide representing a CTL epitope from the human papillomavirus ( HPV ) 16 E7 protein induces a specific CTL response that prevents the outgrowth of HPV16 E7-expressing tumors .", "annotated_text": "Vaccination with a peptide representing a CTL epitope from the human papillomavirus ( HPV ) 16 <protein>E7 protein</protein> induces a specific CTL response that prevents the outgrowth of HPV16 E7-expressing tumors ."}
{"id": "1984", "text": "In contrast , vaccination with a peptide encoding an adenovirus type 5 ( Ad5 ) E1A CTL epitope results in CTL tolerance and enhanced growth of an Ad5 E1A-expressing tumor .", "annotated_text": "In contrast , vaccination with a peptide encoding an adenovirus type 5 ( Ad5 ) E1A CTL epitope results in CTL tolerance and enhanced growth of an Ad5 E1A-expressing tumor ."}
{"id": "1985", "text": "It is unclear why these peptides induce such opposite effects .", "annotated_text": "It is unclear why these peptides induce such opposite effects ."}
{"id": "1986", "text": "To determine whether a difference in pharmacokinetics can explain the functional contrasts , tritiated Ad5 E1A and HPV16 E7 peptides were injected into mice .", "annotated_text": "To determine whether a difference in pharmacokinetics can explain the functional contrasts , tritiated Ad5 E1A and HPV16 E7 peptides were injected into mice ."}
{"id": "1987", "text": "Results show that the tolerizing peptide spread through the body 16 times faster than the activating peptide and was cleared at least 2 times faster .", "annotated_text": "Results show that the tolerizing peptide spread through the body 16 times faster than the activating peptide and was cleared at least 2 times faster ."}
{"id": "1988", "text": "The HPV16 E7 peptide kinetics correlated with the kinetics of HPV16 E7 -specific CTL induction .", "annotated_text": "The HPV16 E7 peptide kinetics correlated with the kinetics of <protein>HPV16 E7</protein> -specific CTL induction ."}
{"id": "1989", "text": "In contrast , Ad5 E1A peptide injection resulted in physical deletion of preexisting Ad5 E1A -specific CTLs within 24 h after injection .", "annotated_text": "In contrast , Ad5 E1A peptide injection resulted in physical deletion of preexisting <protein>Ad5 E1A</protein> -specific <protein>CTLs</protein> within 24 h after injection ."}
{"id": "1990", "text": "This tolerization occurred at the time when the peptide reached its maximum peptide concentration in the organs .", "annotated_text": "This tolerization occurred at the time when the peptide reached its maximum peptide concentration in the organs ."}
{"id": "1991", "text": "These data suggest that ubiquitous expression of the tolerizing Ad5 E1A peptide within a short period of time causes activation-induced cell death of Ad5 E1A -specific CTLs .", "annotated_text": "These data suggest that ubiquitous expression of the tolerizing Ad5 E1A peptide within a short period of time causes activation-induced cell death of <protein>Ad5 E1A</protein> -specific <protein>CTLs</protein> ."}
{"id": "1992", "text": "Therefore , information on the pharmacokinetics of peptides is vital for the safety and efficacy of peptide-based vaccines .", "annotated_text": "Therefore , information on the pharmacokinetics of peptides is vital for the safety and efficacy of peptide-based vaccines ."}
{"id": "1993", "text": "Smad3 and Smad4 mediate transforming growth factor-beta1 -induced IgA expression in murine B lymphocytes .", "annotated_text": "<protein>Smad3</protein> and <protein>Smad4</protein> mediate <protein>transforming growth factor-beta1</protein> -induced IgA expression in <cell_type>murine B lymphocytes</cell_type> ."}
{"id": "1994", "text": "Transforming growth factor ( TGF ) -beta1 is well established as a critical IgA isotype switching factor and Smad molecules have been reported to act as transducers and transcriptional factors in the expression of TGF-beta1 -targeted genes .", "annotated_text": "<protein>Transforming growth factor ( TGF ) -beta1</protein> is well established as a critical <protein>IgA isotype switching factor</protein> and <protein>Smad molecules</protein> have been reported to act as <protein>transducers</protein> and <protein>transcriptional factors</protein> in the expression of <protein>TGF-beta1</protein> -targeted <dna>genes</dna> ."}
{"id": "1995", "text": "We examined the involvement of Smad proteins in TGF-beta1 -induced IgA expression .", "annotated_text": "We examined the involvement of <protein>Smad proteins</protein> in <protein>TGF-beta1</protein> -induced IgA expression ."}
{"id": "1996", "text": "First , we found that TGF-beta1 significantly increases endogenous germ-line ( GL ) alpha transcripts by LPS-stimulated CH12.LX.4933 ( mu ( + ) ) B lymphoma cells .", "annotated_text": "First , we found that <protein>TGF-beta1</protein> significantly increases <rna>endogenous germ-line ( GL ) alpha transcripts</rna> by LPS-stimulated <cell_line>CH12.LX.4933 ( mu ( + ) ) B lymphoma cells</cell_line> ."}
{"id": "1997", "text": "To investigate its signaling mechanisms , the lymphoma cell line was transfected with pFL3 that contains the TGF-beta-responsive element of the GLalpha promoter , and stimulated with TGF-beta1 .", "annotated_text": "To investigate its signaling mechanisms , the <cell_line>lymphoma cell line</cell_line> was transfected with <dna>pFL3</dna> that contains the <dna>TGF-beta-responsive element</dna> of the <dna>GLalpha promoter</dna> , and stimulated with <protein>TGF-beta1</protein> ."}
{"id": "1998", "text": "Similar to endogenous GLalpha transcripts , TGF-beta1 induces GLalpha promoter activity and overexpression of Smad3 markedly enhances the promoter activity .", "annotated_text": "Similar to <rna>endogenous GLalpha transcripts</rna> , <protein>TGF-beta1</protein> induces <dna>GLalpha promoter</dna> activity and overexpression of <protein>Smad3</protein> markedly enhances the promoter activity ."}
{"id": "1999", "text": "This activity is further augmented by cotransfected Smad4 .", "annotated_text": "This activity is further augmented by <protein>cotransfected Smad4</protein> ."}
{"id": "2000", "text": "On the other hand , Smad7 substantially abrogates the synergistic effect of Smad3/4 on GLalpha promoter activity .", "annotated_text": "On the other hand , <protein>Smad7</protein> substantially abrogates the synergistic effect of <protein>Smad3/4</protein> on <dna>GLalpha promoter</dna> activity ."}
{"id": "2001", "text": "In addition , overexpression of Smad3/4 enhances TGF-beta1 -induced endogenous GLalpha transcripts in normal spleen B cell s .", "annotated_text": "In addition , overexpression of <protein>Smad3/4</protein> enhances <protein>TGF-beta1</protein> -induced <rna>endogenous GLalpha transcripts</rna> in <cell_type>normal spleen B cell</cell_type> s ."}
{"id": "2002", "text": "Finally , in the presence of TGF-beta1 , overexpression of Smad3/4 selectively increases both surface IgA expression and IgA production .", "annotated_text": "Finally , in the presence of <protein>TGF-beta1</protein> , overexpression of <protein>Smad3/4</protein> selectively increases both surface IgA expression and IgA production ."}
{"id": "2003", "text": "The results from the present study indicate that Smad3 , Smad4 , and Smad7 , at least in part , serve as mediators linking TGF-beta1 to transcriptional regulation of IgA switching related gene and regulation of IgA class switching .", "annotated_text": "The results from the present study indicate that <protein>Smad3</protein> , <protein>Smad4</protein> , and <protein>Smad7</protein> , at least in part , serve as mediators linking <protein>TGF-beta1</protein> to transcriptional regulation of <dna>IgA switching related gene</dna> and regulation of IgA class switching ."}
{"id": "2004", "text": "The translesion DNA polymerase zeta plays a major role in Ig and bcl-6 somatic hypermutation .", "annotated_text": "The <protein>translesion DNA polymerase zeta</protein> plays a major role in Ig and bcl-6 somatic hypermutation ."}
{"id": "2005", "text": "Ig somatic mutations would be introduced by a polymerase ( pol ) while repairing DNA outside main DNA replication .", "annotated_text": "Ig somatic mutations would be introduced by a <protein>polymerase</protein> ( <protein>pol</protein> ) while repairing DNA outside main DNA replication ."}
{"id": "2006", "text": "We show that human B cells constitutively express the translesion pol zeta , which effectively extends DNA past mismatched bases ( mispair extender ) , and pol eta , which bypasses DNA lesions in an error-free fashion .", "annotated_text": "We show that <cell_type>human B cells</cell_type> constitutively express the <protein>translesion pol zeta</protein> , which effectively extends DNA past mismatched bases ( mispair extender ) , and <protein>pol eta</protein> , which bypasses DNA lesions in an error-free fashion ."}
{"id": "2007", "text": "Upon B cell receptor ( BCR ) engagement and coculture with activated CD4+ T cells , these lymphocytes upregulated pol zeta , downregulated pol eta , and mutated the Ig and bcl-6 genes .", "annotated_text": "Upon <protein>B cell receptor</protein> ( <protein>BCR</protein> ) engagement and coculture with <cell_type>activated CD4+ T cells</cell_type> , these <cell_type>lymphocytes</cell_type> upregulated <protein>pol zeta</protein> , downregulated <protein>pol eta</protein> , and mutated the <dna>Ig and bcl-6 genes</dna> ."}
{"id": "2008", "text": "Inhibition of the pol zeta REV3 catalytic subunit by specific phosphorothioate-modified oligonucleotides impaired Ig and bcl-6 hypermutation and UV damage-induced DNA mutagenesis , without affecting cell cycle or viability .", "annotated_text": "Inhibition of the <protein>pol zeta</protein> <protein>REV3 catalytic subunit</protein> by specific phosphorothioate-modified oligonucleotides impaired Ig and bcl-6 hypermutation and UV damage-induced DNA mutagenesis , without affecting cell cycle or viability ."}
{"id": "2009", "text": "Thus , pol zeta plays a critical role in Ig and bcl-6 hypermutation , perhaps facilitated by the downregulation of pol eta .", "annotated_text": "Thus , <protein>pol zeta</protein> plays a critical role in Ig and bcl-6 hypermutation , perhaps facilitated by the downregulation of <protein>pol eta</protein> ."}
{"id": "2010", "text": "Molecular mechanism of cell cycle progression induced by the oncogene product Tax of human T-cell leukemia virus type I .", "annotated_text": "Molecular mechanism of cell cycle progression induced by the <protein>oncogene product Tax</protein> of human T-cell leukemia virus type I ."}
{"id": "2011", "text": "The trans-activator protein Tax of human T-cell leukemia virus type I ( HTLV-I ) plays an important role in the development of adult T-cell leukemia through , at least in part , its ability to stimulate cell growth .", "annotated_text": "The <protein>trans-activator protein Tax</protein> of human T-cell leukemia virus type I ( HTLV-I ) plays an important role in the development of adult T-cell leukemia through , at least in part , its ability to stimulate cell growth ."}
{"id": "2012", "text": "We previously reported that Tax induced cell cycle progression from G0/G1 phase to S and G2/M phases in human T-cell line Kit 225 cells .", "annotated_text": "We previously reported that <protein>Tax</protein> induced cell cycle progression from G0/G1 phase to S and G2/M phases in <cell_line>human T-cell line Kit 225 cells</cell_line> ."}
{"id": "2013", "text": "To elucidate molecular mechanism of Tax -induced cell cycle progression , we systematically examined the effects of Tax on biochemical events associated with cell cycle progression .", "annotated_text": "To elucidate molecular mechanism of <protein>Tax</protein> -induced cell cycle progression , we systematically examined the effects of <protein>Tax</protein> on biochemical events associated with cell cycle progression ."}
{"id": "2014", "text": "Introduction of Tax into resting Kit 225 cells induced activation of the G1/S transition regulation cascade consisting of activation of cyclin dependent kinase 2 ( CDK2 ) and CDK4 , phosphorylation of the Rb family proteins and an increase in free E2F .", "annotated_text": "Introduction of <protein>Tax</protein> into <cell_line>resting Kit 225 cells</cell_line> induced activation of the G1/S transition regulation cascade consisting of activation of <protein>cyclin dependent kinase 2</protein> ( <protein>CDK2</protein> ) and <protein>CDK4</protein> , phosphorylation of the <protein>Rb family proteins</protein> and an increase in free <protein>E2F</protein> ."}
{"id": "2015", "text": "The kinase activation was found to result from Tax -induced expression of genes for cell cycle regulatory molecules including cyclin D2 , cyclin E , E2F1 , CDK2 , CDK4 and CDK6 , and Tax -induced reduction of CDK inhibitors p19 ( INK4d ) and p27 ( Kip1 ) .", "annotated_text": "The kinase activation was found to result from <protein>Tax</protein> -induced expression of genes for <protein>cell cycle regulatory molecules</protein> including <protein>cyclin D2</protein> , <protein>cyclin E</protein> , <protein>E2F1</protein> , <protein>CDK2</protein> , <protein>CDK4</protein> and <protein>CDK6</protein> , and <protein>Tax</protein> -induced reduction of <protein>CDK inhibitors p19</protein> ( <protein>INK4d</protein> ) and <protein>p27 ( Kip1 )</protein> ."}
{"id": "2016", "text": "These modulations by Tax always paralleled the ability of Tax to activate the NF-kappaB transcription pathway .", "annotated_text": "These modulations by <protein>Tax</protein> always paralleled the ability of <protein>Tax</protein> to activate the NF-kappaB transcription pathway ."}
{"id": "2017", "text": "These results indicate the important role of Tax -mediated trans-activation of the genes for cell cycle regulatory molecules in Tax -induced cell cycle progression .", "annotated_text": "These results indicate the important role of <protein>Tax</protein> -mediated trans-activation of the genes for <protein>cell cycle regulatory molecules</protein> in <protein>Tax</protein> -induced cell cycle progression ."}
{"id": "2018", "text": "Cot kinase induces cyclooxygenase-2 expression in T cells through activation of the nuclear factor of activated T cells .", "annotated_text": "<protein>Cot kinase</protein> induces cyclooxygenase-2 expression in <cell_type>T cells</cell_type> through activation of the <protein>nuclear factor of activated T cells</protein> ."}
{"id": "2019", "text": "Cyclooxygenase-2 ( COX-2 ) is induced in human T lymphocytes upon T cell receptor triggering .", "annotated_text": "<protein>Cyclooxygenase-2</protein> ( <protein>COX-2</protein> ) is induced in <cell_type>human T lymphocytes</cell_type> upon <protein>T cell receptor</protein> triggering ."}
{"id": "2020", "text": "Here we report that Cot kinase , a mitogen-activated protein kinase kinase kinase involved in T cell activation , up-regulates COX-2 gene expression in Jurkat T cells .", "annotated_text": "Here we report that <protein>Cot kinase</protein> , a <protein>mitogen-activated protein kinase kinase kinase</protein> involved in T cell activation , up-regulates <dna>COX-2 gene</dna> expression in <cell_line>Jurkat T cells</cell_line> ."}
{"id": "2021", "text": "Induction of COX-2 promoter activity by Cot kinase occurred mainly through activation of the nuclear factor of activated T cells ( NFAT ) .", "annotated_text": "Induction of COX-2 promoter activity by <protein>Cot kinase</protein> occurred mainly through activation of the <protein>nuclear factor of activated T cells</protein> ( <protein>NFAT</protein> ) ."}
{"id": "2022", "text": "Mutation of the distal ( -105/-97 ) and proximal ( -76/-61 ) NFAT response elements in the COX-2 promoter abolished the activation induced by Cot kinase .", "annotated_text": "Mutation of the <dna>distal ( -105/-97 )</dna> and <dna>proximal ( -76/-61 )</dna> <dna>NFAT response elements</dna> in the <dna>COX-2 promoter</dna> abolished the activation induced by <protein>Cot kinase</protein> ."}
{"id": "2023", "text": "Even more , coexpression of a dominant negative version of NFAT inhibited Cot kinase -mediated COX-2 promoter activation , whereas cotransfection of a constitutively active version of the calcium-dependent phosphatase calcineurin synergizes with Cot kinase in the up-regulation of COX-2 promoter -driven transcription .", "annotated_text": "Even more , coexpression of a dominant negative version of <protein>NFAT</protein> inhibited <protein>Cot kinase</protein> -mediated <dna>COX-2 promoter</dna> activation , whereas cotransfection of a constitutively active version of the <protein>calcium-dependent phosphatase calcineurin</protein> synergizes with <protein>Cot kinase</protein> in the up-regulation of <dna>COX-2 promoter</dna> -driven transcription ."}
{"id": "2024", "text": "Strikingly , Cot kinase increased transactivation mediated by a GAL4-NFAT fusion protein containing the N-terminal transactivation domain of NFATp .", "annotated_text": "Strikingly , <protein>Cot kinase</protein> increased transactivation mediated by a <protein>GAL4-NFAT fusion protein</protein> containing the <protein>N-terminal transactivation domain</protein> of <protein>NFATp</protein> ."}
{"id": "2025", "text": "In contrast to phorbol ester plus calcium ionophore A23187 , Cot kinase increases both COX-2 promoter activity and NFAT -mediated transactivation in a cyclosporin A-independent manner .", "annotated_text": "In contrast to phorbol ester plus calcium ionophore A23187 , <protein>Cot kinase</protein> increases both <dna>COX-2 promoter</dna> activity and <protein>NFAT</protein> -mediated transactivation in a cyclosporin A-independent manner ."}
{"id": "2026", "text": "These data indicate that Cot kinase up-regulates COX-2 promoter -driven transcription through the NFAT response elements , being the Cot kinase -induced NFAT -dependent transactivation presumably implicated in this up-regulation .", "annotated_text": "These data indicate that <protein>Cot kinase</protein> up-regulates <dna>COX-2 promoter</dna> -driven transcription through the <dna>NFAT response elements</dna> , being the <protein>Cot kinase</protein> -induced <protein>NFAT</protein> -dependent transactivation presumably implicated in this up-regulation ."}
{"id": "2027", "text": "Positive and negative roles of the trans-acting T cell factor-1 for the acquisition of distinct Ly-49 MHC class I receptors by NK cells .", "annotated_text": "Positive and negative roles of the <protein>trans-acting T cell factor-1</protein> for the acquisition of distinct <protein>Ly-49 MHC class I receptors</protein> by <cell_type>NK cells</cell_type> ."}
{"id": "2028", "text": "Members of the Ly-49 gene family code for class I MHC-specific receptors that regulate NK cell function .", "annotated_text": "Members of the <dna>Ly-49 gene family</dna> code for <protein>class I MHC-specific receptors</protein> that regulate NK cell function ."}
{"id": "2029", "text": "Due to a combinatorial distribution of Ly-49 receptors , NK cells display considerable clonal heterogeneity .", "annotated_text": "Due to a combinatorial distribution of <protein>Ly-49 receptors</protein> , <cell_type>NK cells</cell_type> display considerable clonal heterogeneity ."}
{"id": "2030", "text": "The acquisition of one Ly-49 receptor , Ly-49A is strictly dependent on the transcriptional trans-acting factor T cell-specific factor-1 ( TCF-1 ) .", "annotated_text": "The acquisition of one <protein>Ly-49 receptor</protein> , <protein>Ly-49A</protein> is strictly dependent on the <protein>transcriptional trans-acting factor</protein> <protein>T cell-specific factor-1</protein> ( <protein>TCF-1</protein> ) ."}
{"id": "2031", "text": "Indeed , TCF-1 binds to two sites in the Ly-49a promoter and regulates its activity , suggesting that the Ly-49a gene is a direct TCF-1 target .", "annotated_text": "Indeed , <protein>TCF-1</protein> binds to two sites in the <dna>Ly-49a promoter</dna> and regulates its activity , suggesting that the <dna>Ly-49a gene</dna> is a direct <protein>TCF-1</protein> target ."}
{"id": "2032", "text": "TCF-1 deficiency resulted in the altered usage of additional Ly-49 receptors .", "annotated_text": "<protein>TCF-1</protein> deficiency resulted in the altered usage of additional <protein>Ly-49 receptors</protein> ."}
{"id": "2033", "text": "We show in this study , using TCF-1 beta ( 2 ) -microglobulin double-deficient mice , that these repertoire alterations are not due to Ly-49/MHC class I interactions .", "annotated_text": "We show in this study , using <protein>TCF-1 beta ( 2 ) -microglobulin</protein> double-deficient mice , that these repertoire alterations are not due to Ly-49/MHC class I interactions ."}
{"id": "2034", "text": "Our findings rather suggest a TCF-1 -dependent , cell autonomous effect on the acquisition of multiple Ly-49 receptors .", "annotated_text": "Our findings rather suggest a <protein>TCF-1</protein> -dependent , cell autonomous effect on the acquisition of multiple <protein>Ly-49 receptors</protein> ."}
{"id": "2035", "text": "Besides reduced receptor usage ( Ly-49A and D ) , we also observed no effect ( Ly-49C ) and significantly expanded ( Ly-49G and I ) receptor usage in the absence of TCF-1 .", "annotated_text": "Besides reduced receptor usage ( <protein>Ly-49A and D</protein> ) , we also observed no effect ( <protein>Ly-49C</protein> ) and significantly expanded ( <protein>Ly-49G and I</protein> ) receptor usage in the absence of <protein>TCF-1</protein> ."}
{"id": "2036", "text": "These effects did not in all cases correlate with the presence of TCF binding sites in the respective proximal promoter .", "annotated_text": "These effects did not in all cases correlate with the presence of <dna>TCF binding sites</dna> in the respective <dna>proximal promoter</dna> ."}
{"id": "2037", "text": "Therefore , besides TCF-1 binding to the proximal promoter , Ly-49 acquisition may also be regulated by TCF-1 binding to more distant cis-acting elements and/or by regulating the expression of additional trans-acting factors .", "annotated_text": "Therefore , besides <protein>TCF-1</protein> binding to the <dna>proximal promoter</dna> , Ly-49 acquisition may also be regulated by <protein>TCF-1</protein> binding to more distant <dna>cis-acting elements</dna> and/or by regulating the expression of additional <dna>trans-acting factors</dna> ."}
{"id": "2038", "text": "Consistent with the observed differential , positive or negative role of TCF-1 for Ly-49 receptor acquisition , reporter gene assays revealed the presence of an inducing as well as a repressing TCF site in certain proximal Ly-49 promoters .", "annotated_text": "Consistent with the observed differential , positive or negative role of <protein>TCF-1</protein> for <protein>Ly-49 receptor</protein> acquisition , reporter gene assays revealed the presence of an inducing as well as a repressing <dna>TCF site</dna> in certain proximal <dna>Ly-49 promoters</dna> ."}
{"id": "2039", "text": "These findings reveal an important role of TCF-1 for the formation of the NK cell receptor repertoire .", "annotated_text": "These findings reveal an important role of <protein>TCF-1</protein> for the formation of the <protein>NK cell receptor</protein> repertoire ."}
{"id": "2040", "text": "Ligation of CD11b and CD11c beta ( 2 ) integrins by antibodies or soluble CD23 induces macrophage inflammatory protein 1alpha ( MIP-1alpha ) and MIP-1beta production in primary human monocytes through a pathway dependent on nuclear factor-kappaB .", "annotated_text": "Ligation of <protein>CD11b</protein> and <protein>CD11c beta ( 2 )</protein> <protein>integrins</protein> by <protein>antibodies</protein> or <protein>soluble CD23</protein> induces <protein>macrophage inflammatory protein 1alpha</protein> ( <protein>MIP-1alpha</protein> ) and <protein>MIP-1beta</protein> production in <cell_type>primary human monocytes</cell_type> through a pathway dependent on <protein>nuclear factor-kappaB</protein> ."}
{"id": "2041", "text": "Chemokines and adhesion molecules such as integrins play a major part in the trafficking , extravasation , and recruitment of leukocytes to inflammatory sites .", "annotated_text": "<protein>Chemokines</protein> and <protein>adhesion molecules</protein> such as <protein>integrins</protein> play a major part in the trafficking , extravasation , and recruitment of <cell_type>leukocytes</cell_type> to inflammatory sites ."}
{"id": "2042", "text": "This study investigated the effects of beta ( 2 ) integrin engagement on chemokine production by freshly isolated human monocytes .", "annotated_text": "This study investigated the effects of beta ( 2 ) integrin engagement on chemokine production by <cell_type>freshly isolated human monocytes</cell_type> ."}
{"id": "2043", "text": "We found that ligation of CD11b or CD11c but not CD11a alpha chains of beta ( 2 ) integrins by antibodies or soluble CD23 ( sCD23 ) fusion proteins rapidly induced transcription and secretion of interleukin 8 , macrophage inflammatory protein ( MIP ) 1alpha , and MIP-1beta .", "annotated_text": "We found that ligation of <protein>CD11b</protein> or <protein>CD11c</protein> but not <protein>CD11a alpha chains</protein> of <protein>beta ( 2 ) integrins</protein> by <protein>antibodies</protein> or <protein>soluble CD23 ( sCD23 ) fusion proteins</protein> rapidly induced transcription and secretion of <protein>interleukin 8</protein> , <protein>macrophage inflammatory protein ( MIP ) 1alpha</protein> , and <protein>MIP-1beta</protein> ."}
{"id": "2044", "text": "Because the promoters of these chemokine genes contain kappaB binding sites , we assessed the possible role of nuclear factor-kappaB ( NF-kappaB ) in controlling induction of the genes through beta ( 2 ) integrin engagement .", "annotated_text": "Because the <dna>promoters</dna> of these <dna>chemokine genes</dna> contain <dna>kappaB binding sites</dna> , we assessed the possible role of <protein>nuclear factor-kappaB</protein> ( <protein>NF-kappaB</protein> ) in controlling induction of the genes through beta ( 2 ) integrin engagement ."}
{"id": "2045", "text": "Electrophoretic mobility shift assays showed that sCD23 or antibodies to CD11b or to CD11c up-regulated DNA-binding activity of NF-kappaB .", "annotated_text": "Electrophoretic mobility shift assays showed that <protein>sCD23</protein> or <protein>antibodies</protein> to <protein>CD11b</protein> or to <protein>CD11c</protein> up-regulated DNA-binding activity of <protein>NF-kappaB</protein> ."}
{"id": "2046", "text": "Activation of NF-kappaB was accompanied by degradation of its cytosolic inhibitor IkappaB-alpha .", "annotated_text": "Activation of <protein>NF-kappaB</protein> was accompanied by degradation of its <protein>cytosolic inhibitor IkappaB-alpha</protein> ."}
{"id": "2047", "text": "Blockade of depletion of IkappaB-alpha by proteasome inhibitors ( proteasome inhibitor I or acetyl-leucinyl-leucinyl-norleucinal ) led to concomitant inhibition of NF-kappaB DNA-binding activity and expression of MIP-1alpha and MIP-1beta messenger RNA induced by beta ( 2 ) integrin ligation .", "annotated_text": "Blockade of depletion of <protein>IkappaB-alpha</protein> by proteasome inhibitors ( proteasome inhibitor I or acetyl-leucinyl-leucinyl-norleucinal ) led to concomitant inhibition of NF-kappaB DNA-binding activity and expression of <rna>MIP-1alpha and MIP-1beta messenger RNA</rna> induced by beta ( 2 ) integrin ligation ."}
{"id": "2048", "text": "These results suggest that triggering of CD11b or CD11c beta ( 2 ) integrin on primary human monocytes provides activation signals leading to nuclear translocation of NF-kappaB and subsequent secretion of MIP-1alpha and MIP-1beta that may have an important role in recruitment of other inflammatory cells during initiation of an inflammatory response", "annotated_text": "These results suggest that triggering of <protein>CD11b</protein> or <protein>CD11c beta ( 2 )</protein> integrin on <cell_type>primary human monocytes</cell_type> provides activation signals leading to nuclear translocation of <protein>NF-kappaB</protein> and subsequent secretion of <protein>MIP-1alpha</protein> and <protein>MIP-1beta</protein> that may have an important role in recruitment of other <cell_type>inflammatory cells</cell_type> during initiation of an inflammatory response"}
{"id": "2049", "text": "Synergistic transcriptional activation of human Acyl-coenzyme A : cholesterol acyltransterase-1 gene by interferon-gamma and all-trans-retinoic acid THP-1 cells .", "annotated_text": "Synergistic transcriptional activation of <dna>human Acyl-coenzyme A : cholesterol acyltransterase-1 gene</dna> by <protein>interferon-gamma</protein> and all-trans-retinoic acid <cell_type>THP-1 cells</cell_type> ."}
{"id": "2050", "text": "Acyl-coenzyme A : cholesterol acyltransferase ( ACAT ) is an intracellular enzyme involved in cellular cholesterol homeostasis and in atherosclerotic foam cell formation .", "annotated_text": "<protein>Acyl-coenzyme A : cholesterol acyltransferase</protein> ( <protein>ACAT</protein> ) is an <protein>intracellular enzyme</protein> involved in cellular cholesterol homeostasis and in atherosclerotic foam cell formation ."}
{"id": "2051", "text": "Human ACAT-1 gene contains two promoters ( P1 and P7 ) , each located in a different chromosome ( 1 and 7 ) ( Li , B. L. , Li , X. L. , Duan , Z. J. , Lee , O. , Lin , S. , Ma , Z. M. , Chang , C. C. , Yang , X. Y. , Park , J. P. , Mohandas , T. K. , Noll , W. , Chan , L. , and Chang , T. Y. ( 1999 ) J. Biol Chem. 274 , 11060-11071 ) .", "annotated_text": "<dna>Human ACAT-1 gene</dna> contains two <dna>promoters</dna> ( <dna>P1</dna> and <dna>P7</dna> ) , each located in a different <dna>chromosome ( 1 and 7 )</dna> ( Li , B. L. , Li , X. L. , Duan , Z. J. , Lee , O. , Lin , S. , Ma , Z. M. , Chang , C. C. , Yang , X. Y. , Park , J. P. , Mohandas , T. K. , Noll , W. , Chan , L. , and Chang , T. Y. ( 1999 ) J. Biol Chem. 274 , 11060-11071 ) ."}
{"id": "2052", "text": "Interferon-gamma ( IFN-gamma ) , a cytokine that exerts many pro-atherosclerotic effects in vivo , causes up-regulation of ACAT-1 mRNA in human blood monocyte-derived macrophages and macrophage-like cells but not in other cell types .", "annotated_text": "<protein>Interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) , a <protein>cytokine</protein> that exerts many pro-atherosclerotic effects in vivo , causes up-regulation of <rna>ACAT-1 mRNA</rna> in <cell_type>human blood monocyte-derived macrophages</cell_type> and <cell_type>macrophage-like cells</cell_type> but not in other cell types ."}
{"id": "2053", "text": "To examine the molecular nature of this observation , we identified within the ACAT-1 P1 promoter a 159-base pair core region .", "annotated_text": "To examine the molecular nature of this observation , we identified within the <dna>ACAT-1 P1 promoter</dna> a <dna>159-base pair core region</dna> ."}
{"id": "2054", "text": "This region contains 4 Sp1 elements and an IFN-gamma activated sequence ( GAS ) that overlaps with the second Sp1 element .", "annotated_text": "This region contains 4 <dna>Sp1 elements</dna> and an <dna>IFN-gamma activated sequence</dna> ( <dna>GAS</dna> ) that overlaps with the second <dna>Sp1 element</dna> ."}
{"id": "2055", "text": "In the monocytic cell line THP-1 cell , the combination of IFN-gamma and all-trans-retinoic acid ( a known differentiation agent ) enhances the ACAT-1 P1 promoter but not the P7 promoter .", "annotated_text": "In the <cell_type>monocytic cell line THP-1 cell</cell_type> , the combination of <protein>IFN-gamma</protein> and all-trans-retinoic acid ( a known differentiation agent ) enhances the <dna>ACAT-1 P1 promoter</dna> but not the <dna>P7 promoter</dna> ."}
{"id": "2056", "text": "Additional experiments showed that all-trans-retinoic acid causes large induction of the transcription factor STAT1 , while IFN-gamma causes activation of STAT1 such that it binds to the GAS/Sp1 site in the ACAT-1 P1 promoter .", "annotated_text": "Additional experiments showed that all-trans-retinoic acid causes large induction of the <protein>transcription factor STAT1</protein> , while <protein>IFN-gamma</protein> causes activation of <protein>STAT1</protein> such that it binds to the <dna>GAS/Sp1 site</dna> in the <dna>ACAT-1 P1 promoter</dna> ."}
{"id": "2057", "text": "Our work provides a molecular mechanism to account for the effect of IFN-gamma in causing transcriptional activation of ACAT-1 in macrophage-like cells .", "annotated_text": "Our work provides a molecular mechanism to account for the effect of <protein>IFN-gamma</protein> in causing transcriptional activation of <protein>ACAT-1</protein> in <cell_type>macrophage-like cells</cell_type> ."}
{"id": "2058", "text": "Inhaled nitric oxide down-regulates intrapulmonary nitric oxide production in lipopolysaccharide-induced acute lung injury .", "annotated_text": "Inhaled nitric oxide down-regulates intrapulmonary nitric oxide production in lipopolysaccharide-induced acute lung injury ."}
{"id": "2059", "text": "OBJECTIVE : To examine whether inhaled nitric oxide ( NO ) affected the intrapulmonary production of NO , reactive oxygen species , and nuclear factor-kappaB in a lipopolysaccharide ( LPS ) -induced model of acute lung injury .", "annotated_text": "OBJECTIVE : To examine whether inhaled nitric oxide ( NO ) affected the intrapulmonary production of NO , reactive oxygen species , and <protein>nuclear factor-kappaB</protein> in a lipopolysaccharide ( LPS ) -induced model of acute lung injury ."}
{"id": "2060", "text": "DESIGN : Prospective , randomized , laboratory study .", "annotated_text": "DESIGN : Prospective , randomized , laboratory study ."}
{"id": "2061", "text": "SETTING : Experimental laboratory at a biomedical institute .", "annotated_text": "SETTING : Experimental laboratory at a biomedical institute ."}
{"id": "2062", "text": "SUBJECTS : Twenty male rabbits weighing 2.5-3.5 kg .", "annotated_text": "SUBJECTS : Twenty male rabbits weighing 2.5-3.5 kg ."}
{"id": "2063", "text": "INTERVENTIONS : Saline or LPS ( 5 mg/kg of body weight ) was administered intravenously with or without NO inhalation ( 10 ppm ) in each group of five rabbits .", "annotated_text": "INTERVENTIONS : Saline or LPS ( 5 mg/kg of body weight ) was administered intravenously with or without NO inhalation ( 10 ppm ) in each group of five rabbits ."}
{"id": "2064", "text": "MEASUREMENTS AND MAIN RESULTS : LPS increased the lung leak index , the neutrophils and NO levels in bronchoalveolar lavage fluid , and NO levels produced by resting and stimulated alveolar macrophages .", "annotated_text": "MEASUREMENTS AND MAIN RESULTS : LPS increased the lung leak index , the <cell_type>neutrophils</cell_type> and NO levels in bronchoalveolar lavage fluid , and NO levels produced by resting and stimulated <cell_type>alveolar macrophages</cell_type> ."}
{"id": "2065", "text": "Inhaled NO decreased the lung leak index , the neutrophils and NO levels as measured by nitrite levels in the lavage fluid , and NO produced by the resting and stimulated alveolar macrophages .", "annotated_text": "Inhaled NO decreased the lung leak index , the <cell_type>neutrophils</cell_type> and NO levels as measured by nitrite levels in the lavage fluid , and NO produced by the resting and stimulated <cell_type>alveolar macrophages</cell_type> ."}
{"id": "2066", "text": "Inhaled NO also blocked the activities of reactive oxygen species and nuclear factor-kappaB binding to DNA in lavage cells and in alveolar macrophages .", "annotated_text": "Inhaled NO also blocked the activities of reactive oxygen species and <protein>nuclear factor-kappaB</protein> binding to DNA in <cell_type>lavage cells</cell_type> and in <cell_type>alveolar macrophages</cell_type> ."}
{"id": "2067", "text": "CONCLUSION : Inhaled NO attenuates LPS-induced acute lung injury , possibly by decreasing NO production in the lungs .", "annotated_text": "CONCLUSION : Inhaled NO attenuates LPS-induced acute lung injury , possibly by decreasing NO production in the lungs ."}
{"id": "2068", "text": "The mechanism of reducing NO production resulting from inhaled NO may involve , in part , the activities of reactive oxygen species and/or nuclear factor-kappaB .", "annotated_text": "The mechanism of reducing NO production resulting from inhaled NO may involve , in part , the activities of reactive oxygen species and/or <protein>nuclear factor-kappaB</protein> ."}
{"id": "2069", "text": "Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression .", "annotated_text": "Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of <dna>GATA-3</dna> expression ."}
{"id": "2070", "text": "Recent studies in transgenic mice have revealed that expression of a dominant negative form of the transcription factor GATA-3 in T cells can prevent T helper cell type 2 ( Th2 ) -mediated allergic airway inflammation in mice .", "annotated_text": "Recent studies in transgenic mice have revealed that expression of a dominant negative form of the <protein>transcription factor GATA-3</protein> in <cell_type>T cells</cell_type> can prevent <cell_type>T helper cell type 2</cell_type> ( <cell_type>Th2</cell_type> ) -mediated allergic airway inflammation in mice ."}
{"id": "2071", "text": "However , it remains unclear whether GATA-3 plays a role in the effector phase of allergic airway inflammation and whether antagonizing the expression and/or function of GATA-3 can be used for the therapy of allergic airway inflammation and hyperresponsiveness .", "annotated_text": "However , it remains unclear whether <protein>GATA-3</protein> plays a role in the effector phase of allergic airway inflammation and whether antagonizing the expression and/or function of <dna>GATA-3</dna> can be used for the therapy of allergic airway inflammation and hyperresponsiveness ."}
{"id": "2072", "text": "Here , we analyzed the effects of locally antagonizing GATA-3 function in a murine model of asthma .", "annotated_text": "Here , we analyzed the effects of locally antagonizing <protein>GATA-3</protein> function in a murine model of asthma ."}
{"id": "2073", "text": "We could suppress GATA-3 expression in interleukin ( IL ) -4 -producing T cells in vitro and in vivo by an antisense phosphorothioate oligonucleotide overlapping the translation start site of GATA-3 , whereas nonsense control oligonucleotides were virtually inactive .", "annotated_text": "We could suppress GATA-3 expression in <protein>interleukin ( IL ) -4</protein> -producing <cell_type>T cells</cell_type> in vitro and in vivo by an antisense phosphorothioate oligonucleotide overlapping the <dna>translation start site</dna> of <dna>GATA-3</dna> , whereas nonsense control oligonucleotides were virtually inactive ."}
{"id": "2074", "text": "In a murine model of asthma associated with allergic pulmonary inflammation and hyperresponsiveness in ovalbumin ( OVA ) -sensitized mice , local intranasal administration of fluorescein isothiocyanate-labeled GATA-3 antisense oligonucleotides led to DNA uptake in lung cells associated with a reduction of intracellular GATA-3 expression .", "annotated_text": "In a murine model of asthma associated with allergic pulmonary inflammation and hyperresponsiveness in ovalbumin ( OVA ) -sensitized mice , local intranasal administration of fluorescein isothiocyanate-labeled GATA-3 antisense oligonucleotides led to DNA uptake in <cell_type>lung cells</cell_type> associated with a reduction of intracellular GATA-3 expression ."}
{"id": "2075", "text": "Such intrapulmonary blockade of GATA-3 expression caused an abrogation of signs of lung inflammation including infiltration of eosinophils and Th2 cytokine production .", "annotated_text": "Such intrapulmonary blockade of GATA-3 expression caused an abrogation of signs of lung inflammation including infiltration of <cell_type>eosinophils</cell_type> and <cell_type>Th2</cell_type> cytokine production ."}
{"id": "2076", "text": "Furthermore , treatment with antisense but not nonsense oligonucleotides induced a significant reduction of airway hyperresponsiveness in OVA-sensitized mice to levels comparable to saline-treated control mice , as assessed by both enhanced pause ( PenH ) responses and pulmonary resistance determined by body plethysmography .", "annotated_text": "Furthermore , treatment with antisense but not nonsense oligonucleotides induced a significant reduction of airway hyperresponsiveness in OVA-sensitized mice to levels comparable to saline-treated control mice , as assessed by both enhanced pause ( PenH ) responses and pulmonary resistance determined by body plethysmography ."}
{"id": "2077", "text": "These data indicate a critical role for GATA-3 in the effector phase of a murine asthma model and suggest that local delivery of GATA-3 antisense oligonucleotides may be a novel approach for the treatment of airway hyperresponsiveness such as in asthma .", "annotated_text": "These data indicate a critical role for <dna>GATA-3</dna> in the effector phase of a murine asthma model and suggest that local delivery of GATA-3 antisense oligonucleotides may be a novel approach for the treatment of airway hyperresponsiveness such as in asthma ."}
{"id": "2078", "text": "This approach has the potential advantage of suppressing the expression of various proinflammatory Th2 cytokines simultaneously rather than suppressing the activity of a single cytokine .", "annotated_text": "This approach has the potential advantage of suppressing the expression of various <protein>proinflammatory Th2 cytokines</protein> simultaneously rather than suppressing the activity of a single <protein>cytokine</protein> ."}
{"id": "2079", "text": "T helper-cell phenotype regulates atherosclerosis in mice under conditions of mild hypercholesterolemia .", "annotated_text": "T helper-cell phenotype regulates atherosclerosis in mice under conditions of mild hypercholesterolemia ."}
{"id": "2080", "text": "BACKGROUND : T cells are implicated in atherosclerosis , but little is known about the genetic control or molecular pathways , especially under conditions of mild hypercholesterolemia .", "annotated_text": "BACKGROUND : <cell_type>T cells</cell_type> are implicated in atherosclerosis , but little is known about the genetic control or molecular pathways , especially under conditions of mild hypercholesterolemia ."}
{"id": "2081", "text": "METHODS AND RESULTS : BALB/c mice , making a CD4+ Th2 ( IL-4+ ) cell response , express both MHC class II antigens ( IA ( d ) , IE ( d ) ) and are atherosclerosis-resistant .", "annotated_text": "METHODS AND RESULTS : BALB/c mice , making a CD4+ Th2 ( IL-4+ ) cell response , express both <protein>MHC class II antigens</protein> ( <protein>IA ( d )</protein> , <protein>IE ( d )</protein> ) and are atherosclerosis-resistant ."}
{"id": "2082", "text": "C57Bl/6 mice produce a CD4+ Th1 ( interferon [ IFN ] gamma+ ) response , express IA ( b ) but no IE , and are atherosclerosis-prone .", "annotated_text": "C57Bl/6 mice produce a CD4+ Th1 ( interferon [ IFN ] gamma+ ) response , express <protein>IA ( b )</protein> but no <protein>IE</protein> , and are atherosclerosis-prone ."}
{"id": "2083", "text": "To evaluate T helper-cell phenotype in fatty streak formation , wild-type C57Bl/6 mice ( IA ( b ) +IE- ) and transgenic mice , either AB ( o ) , IA ( b ) -IE- ; ABEalpha , IA-IE ( k ) + ; or BL : TG : Ealpha , IA ( b ) +IE ( k ) + , were fed a high-cholesterol diet for 16 weeks and evaluated histomorphometrically for aortic lesions .", "annotated_text": "To evaluate T helper-cell phenotype in fatty streak formation , wild-type C57Bl/6 mice ( IA ( b ) +IE- ) and transgenic mice , either AB ( o ) , IA ( b ) -IE- ; ABEalpha , IA-IE ( k ) + ; or BL : TG : Ealpha , IA ( b ) +IE ( k ) + , were fed a high-cholesterol diet for 16 weeks and evaluated histomorphometrically for aortic lesions ."}
{"id": "2084", "text": "Lesion size in AB ( o ) , ABEalpha , and BL : TG : Ealpha strains was decreased by 54 % , 79 % , and 82 % , respectively , compared with wild-type , correlating with decreased Th1 and increased Th2 expression and suggesting that T helper-cell phenotype is important in fatty lesion development .", "annotated_text": "Lesion size in AB ( o ) , ABEalpha , and BL : TG : Ealpha strains was decreased by 54 % , 79 % , and 82 % , respectively , compared with wild-type , correlating with decreased <cell_type>Th1</cell_type> and increased <cell_type>Th2</cell_type> expression and suggesting that T helper-cell phenotype is important in fatty lesion development ."}
{"id": "2085", "text": "Decreasing Th1 cells by antibodies ( alpha-CD4 ) or cytokines ( IL-4 ) also caused > /=80 % reductions in lesion size .", "annotated_text": "Decreasing <cell_type>Th1 cells</cell_type> by <protein>antibodies</protein> ( <protein>alpha-CD4</protein> ) or <protein>cytokines</protein> ( <protein>IL-4</protein> ) also caused > /=80 % reductions in lesion size ."}
{"id": "2086", "text": "Immunohistology revealed IFN-gamma , but not IL-4 , colocalized with activated macrophages .", "annotated_text": "Immunohistology revealed <protein>IFN-gamma</protein> , but not <protein>IL-4</protein> , colocalized with activated <cell_type>macrophages</cell_type> ."}
{"id": "2087", "text": "Confirming these findings in a different mouse strain , BALB/c Stat 6 knockout mice ( Th2 cell-deficient ) developed aortic lesions comparable to C57Bl/6 mice on the same diet .", "annotated_text": "Confirming these findings in a different mouse strain , BALB/c Stat 6 knockout mice ( Th2 cell-deficient ) developed aortic lesions comparable to C57Bl/6 mice on the same diet ."}
{"id": "2088", "text": "CONCLUSIONS : In mildly hypercholesterolemic C57Bl/6 mice , presence of IA ( b ) and absence of IE regulated CD4+ T helper-cell phenotype ; fatty lesions were proportional to IFNgamma+ Th1 cells in both C57Bl/6 and BALB/c strains .", "annotated_text": "CONCLUSIONS : In mildly hypercholesterolemic C57Bl/6 mice , presence of <protein>IA ( b )</protein> and absence of <protein>IE</protein> regulated CD4+ T helper-cell phenotype ; fatty lesions were proportional to <cell_type>IFNgamma+ Th1 cells</cell_type> in both C57Bl/6 and BALB/c strains ."}
{"id": "2089", "text": "IFN-gamma may participate through macrophage activation , whereas IL-4 may act to limit Th1-cell response .", "annotated_text": "<protein>IFN-gamma</protein> may participate through macrophage activation , whereas <protein>IL-4</protein> may act to limit Th1-cell response ."}
{"id": "2090", "text": "Requirement for p38 and p44/p42 mitogen-activated protein kinases in RAGE -mediated nuclear factor-kappaB transcriptional activation and cytokine secretion .", "annotated_text": "Requirement for <protein>p38</protein> and <protein>p44/p42</protein> <protein>mitogen-activated protein kinases</protein> in <protein>RAGE</protein> -mediated <protein>nuclear factor-kappaB</protein> transcriptional activation and cytokine secretion ."}
{"id": "2091", "text": "Advanced glycation end product ( AGE ) activation of the signal-transducing receptor for AGE ( RAGE ) has been linked to a proinflammatory phenotypic change within cells .", "annotated_text": "Advanced glycation end product ( AGE ) activation of the <protein>signal-transducing receptor for AGE</protein> ( <protein>RAGE</protein> ) has been linked to a proinflammatory phenotypic change within cells ."}
{"id": "2092", "text": "However , the precise intracellular signaling pathways involved have not been elucidated .", "annotated_text": "However , the precise intracellular signaling pathways involved have not been elucidated ."}
{"id": "2093", "text": "We demonstrate here that human serum albumin modified with N ( varepsilon ) - ( carboxymethyl ) lysine ( CML ) , a major AGE adduct that progressively accumulates with aging , diabetes , and renal failure , induced nuclear factor ( NF ) -kappaB -driven reporter gene expression in human monocytic THP-1 cells .", "annotated_text": "We demonstrate here that human serum albumin modified with N ( varepsilon ) - ( carboxymethyl ) lysine ( CML ) , a major AGE adduct that progressively accumulates with aging , diabetes , and renal failure , induced <protein>nuclear factor ( NF ) -kappaB</protein> -driven reporter gene expression in <cell_type>human monocytic THP-1 cells</cell_type> ."}
{"id": "2094", "text": "The NF-kappaB response was blocked with a synthetic peptide corresponding to the putative ligand-binding domain of RAGE , with anti- RAGE antiserum , and by coexpression of truncated receptors lacking the intracellular domain .", "annotated_text": "The NF-kappaB response was blocked with a synthetic peptide corresponding to the <protein>putative ligand-binding domain</protein> of <protein>RAGE</protein> , with anti- <protein>RAGE</protein> antiserum , and by coexpression of <protein>truncated receptors</protein> lacking the <protein>intracellular domain</protein> ."}
{"id": "2095", "text": "Signal transduction from RAGE to NF-kappaB involved the generation of reactive oxygen species , since reporter gene expression was blocked with the antioxidant N-acetyl-L-cysteine .", "annotated_text": "Signal transduction from <protein>RAGE</protein> to <protein>NF-kappaB</protein> involved the generation of reactive oxygen species , since reporter gene expression was blocked with the antioxidant N-acetyl-L-cysteine ."}
{"id": "2096", "text": "CML-modified albumin produced rapid transient activation of tyrosine phosphorylation , extracellular signal-regulated kinase 1 and 2 , and p38 mitogen-activated protein kinase ( MAPK ) , but not c-Jun NH ( 2 ) -terminal kinase .", "annotated_text": "<protein>CML-modified albumin</protein> produced rapid transient activation of tyrosine phosphorylation , <protein>extracellular signal-regulated kinase 1 and 2</protein> , and <protein>p38 mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) , but not <protein>c-Jun NH ( 2 ) -terminal kinase</protein> ."}
{"id": "2097", "text": "RAGE -mediated NF-kappaB activation was suppressed by the selective p38 MAPK inhibitor SB203580 and by coexpression of a kinase-dead p38 dominant-negative mutant .", "annotated_text": "<protein>RAGE</protein> -mediated NF-kappaB activation was suppressed by the selective <protein>p38 MAPK</protein> inhibitor SB203580 and by coexpression of a kinase-dead p38 dominant-negative mutant ."}
{"id": "2098", "text": "Activation of NF-kappaB by CML-modified albumin increased secretion of proinflammatory cytokines ( tumor necrosis factor-alpha , interleukin-1beta , and monocyte chemoattractant protein-1 ) severalfold , and inhibition of p38 MAPK blocked these increases .", "annotated_text": "Activation of <protein>NF-kappaB</protein> by <protein>CML-modified albumin</protein> increased secretion of <protein>proinflammatory cytokines</protein> ( <protein>tumor necrosis factor-alpha</protein> , <protein>interleukin-1beta</protein> , and <protein>monocyte chemoattractant protein-1</protein> ) severalfold , and inhibition of <protein>p38 MAPK</protein> blocked these increases ."}
{"id": "2099", "text": "These results indicate that p38 MAPK activation mediates RAGE -induced NF-kappaB -dependent secretion of proinflammatory cytokines and suggest that accelerated inflammation may be a consequence of cellular activation induced by this receptor .", "annotated_text": "These results indicate that <protein>p38 MAPK</protein> activation mediates <protein>RAGE</protein> -induced <protein>NF-kappaB</protein> -dependent secretion of <protein>proinflammatory cytokines</protein> and suggest that accelerated inflammation may be a consequence of cellular activation induced by this receptor ."}
{"id": "2100", "text": "Antigen-receptor cross-linking and lipopolysaccharide trigger distinct phosphoinositide 3-kinase -dependent pathways to NF-kappa B activation in primary B cells .", "annotated_text": "Antigen-receptor cross-linking and lipopolysaccharide trigger distinct <protein>phosphoinositide 3-kinase</protein> -dependent pathways to NF-kappa B activation in <cell_type>primary B cells</cell_type> ."}
{"id": "2101", "text": "The NF-kappaB/Rel transcription factors play an important role in the expression of genes involved in B cell development , differentiation and function .", "annotated_text": "The <protein>NF-kappaB/Rel transcription factors</protein> play an important role in the expression of genes involved in B cell development , differentiation and function ."}
{"id": "2102", "text": "Nuclear NF-kappaB is induced in B cells by engagement of either the BCR or CD40 or by stimulation with lipopolysaccharide ( LPS ) .", "annotated_text": "<protein>Nuclear NF-kappaB</protein> is induced in <cell_type>B cells</cell_type> by engagement of either the <protein>BCR</protein> or <protein>CD40</protein> or by stimulation with lipopolysaccharide ( LPS ) ."}
{"id": "2103", "text": "Despite the importance of NF-kappaB to B cell function , little is known about the signaling pathways leading to NF-kappaB activation .", "annotated_text": "Despite the importance of <protein>NF-kappaB</protein> to B cell function , little is known about the signaling pathways leading to NF-kappaB activation ."}
{"id": "2104", "text": "In this report we address the role of phosphoinositide 3'-kinase ( PI 3-kinase ) in BCR - and LPS-induced NF-kappaB activation using populations of primary murine resting B cells .", "annotated_text": "In this report we address the role of <protein>phosphoinositide 3'-kinase</protein> ( <protein>PI 3-kinase</protein> ) in <protein>BCR</protein> - and LPS-induced NF-kappaB activation using populations of <cell_type>primary murine resting B cells</cell_type> ."}
{"id": "2105", "text": "Using the specific pharmacological inhibitors of PI 3-kinase , Wortmannin and LY294002 , we demonstrate that PI 3-kinase activity is vital for BCR -induced NF-kappaB DNA-binding activity .", "annotated_text": "Using the specific pharmacological inhibitors of <protein>PI 3-kinase</protein> , Wortmannin and LY294002 , we demonstrate that <protein>PI 3-kinase</protein> activity is vital for <protein>BCR</protein> -induced <protein>NF-kappaB</protein> DNA-binding activity ."}
{"id": "2106", "text": "Furthermore , we show that this is achieved via protein kinase C -dependent degradation of IkappaBalpha .", "annotated_text": "Furthermore , we show that this is achieved via <protein>protein kinase C</protein> -dependent degradation of <protein>IkappaBalpha</protein> ."}
{"id": "2107", "text": "Similar analyses reveal that PI 3-kinase is also critical in triggering NF-kappaB DNA-binding activity and IkappaBalpha degradation following LPS stimulation .", "annotated_text": "Similar analyses reveal that <protein>PI 3-kinase</protein> is also critical in triggering <protein>NF-kappaB</protein> DNA-binding activity and <protein>IkappaBalpha</protein> degradation following LPS stimulation ."}
{"id": "2108", "text": "Interestingly , a PKC inhibitor which blocked the BCR -induced IkappaBalpha degradation had no effect on the degradation of IkappaBalpha after LPS stimulation .", "annotated_text": "Interestingly , a PKC inhibitor which blocked the <protein>BCR</protein> -induced <protein>IkappaBalpha</protein> degradation had no effect on the degradation of <protein>IkappaBalpha</protein> after LPS stimulation ."}
{"id": "2109", "text": "Taken together , our results indicate the involvement of PI 3-kinase in at least two distinct signaling pathways leading to activation of NF-kappaB in B cells .", "annotated_text": "Taken together , our results indicate the involvement of <protein>PI 3-kinase</protein> in at least two distinct signaling pathways leading to activation of <protein>NF-kappaB</protein> in <cell_type>B cells</cell_type> ."}
{"id": "2110", "text": "Tetramer-guided epitope mapping : rapid identification and characterization of immunodominant CD4+ T cell epitopes from complex antigens .", "annotated_text": "Tetramer-guided epitope mapping : rapid identification and characterization of <cell_type>immunodominant CD4+ T cell epitopes</cell_type> from complex <protein>antigens</protein> ."}
{"id": "2111", "text": "T cell responses to Ags involve recognition of selected peptide epitopes contained within the antigenic protein .", "annotated_text": "T cell responses to <protein>Ags</protein> involve recognition of selected <protein>peptide epitopes</protein> contained within the <protein>antigenic protein</protein> ."}
{"id": "2112", "text": "In this report , we describe a new approach for direct identification of CD4+ T cell epitopes of complex Ags that uses human class II tetramers to identify reactive cells .", "annotated_text": "In this report , we describe a new approach for direct identification of <cell_type>CD4+ T cell epitopes</cell_type> of complex <protein>Ags</protein> that uses <protein>human class II tetramers</protein> to identify reactive cells ."}
{"id": "2113", "text": "With a panel of 60 overlapping peptides covering the entire sequence of the VP16 protein , a major Ag for HSV-2 , we generated a panel of class II MHC tetramers loaded with peptide pools that were used to stain peripheral lymphocytes of an HSV-2 infected individual .", "annotated_text": "With a panel of 60 overlapping peptides covering the entire sequence of the <protein>VP16 protein</protein> , a major <protein>Ag</protein> for HSV-2 , we generated a panel of <protein>class II MHC tetramers</protein> loaded with peptide pools that were used to stain <cell_type>peripheral lymphocytes</cell_type> of an HSV-2 infected individual ."}
{"id": "2114", "text": "With this approach , we identified four new DRA1*0101/DRB1*0401- and two DRA1*0101/DRB1*0404-restricted , VP16-specific epitopes .", "annotated_text": "With this approach , we identified four new DRA1*0101/DRB1*0401- and two DRA1*0101/DRB1*0404-restricted , <protein>VP16-specific epitopes</protein> ."}
{"id": "2115", "text": "By using tetramers to sort individual cells , we easily obtained a large number of clones specific to these epitopes .", "annotated_text": "By using <protein>tetramers</protein> to sort individual cells , we easily obtained a large number of clones specific to these <protein>epitopes</protein> ."}
{"id": "2116", "text": "Although DRA1*0101/DRB1*0401 and DRA1*0101/DRB1*0404 are structurally very similar , nonoverlapping VP16 epitopes were identified , illustrating high selectivity of individual allele polymorphisms within common MHC variants .", "annotated_text": "Although DRA1*0101/DRB1*0401 and DRA1*0101/DRB1*0404 are structurally very similar , nonoverlapping <protein>VP16 epitopes</protein> were identified , illustrating high selectivity of individual allele polymorphisms within common MHC variants ."}
{"id": "2117", "text": "This rapid approach to detecting CD4+ T cell epitopes from complex Ags can be applied to any known Ag that gives a T cell response .", "annotated_text": "This rapid approach to detecting <cell_type>CD4+ T cell epitopes</cell_type> from complex <protein>Ags</protein> can be applied to any known <protein>Ag</protein> that gives a T cell response ."}
{"id": "2118", "text": "Localized pancreatic NF-kappaB activation and inflammatory response in taurocholate-induced pancreatitis .", "annotated_text": "Localized pancreatic NF-kappaB activation and inflammatory response in taurocholate-induced pancreatitis ."}
{"id": "2119", "text": "Transcription factor nuclear factor-kappaB ( NF-kappaB ) is activated in cerulein pancreatitis and mediates cytokine expression .", "annotated_text": "<protein>Transcription factor nuclear factor-kappaB</protein> ( <protein>NF-kappaB</protein> ) is activated in cerulein pancreatitis and mediates cytokine expression ."}
{"id": "2120", "text": "The role of transcription factor activation in other models of pancreatitis has not been established .", "annotated_text": "The role of transcription factor activation in other models of pancreatitis has not been established ."}
{"id": "2121", "text": "Here we report upregulation of NF-kappaB and inflammatory molecules , and their correlation with local pancreatic injury , in a model of severe pancreatitis .", "annotated_text": "Here we report upregulation of <protein>NF-kappaB</protein> and <protein>inflammatory molecules</protein> , and their correlation with local pancreatic injury , in a model of severe pancreatitis ."}
{"id": "2122", "text": "Rats received intraductal infusion of taurocholate or saline , and the pancreatic head and tail were analyzed separately .", "annotated_text": "Rats received intraductal infusion of taurocholate or saline , and the pancreatic head and tail were analyzed separately ."}
{"id": "2123", "text": "NF-kappaB and activator protein-1 ( AP-1 ) activation were assessed by gel shift assay , and mRNA expression of interleukin-6 , tumor necrosis factor-alpha , KC , monocyte chemoattractant protein-1 , and inducible nitric oxide synthase was assessed by semiquantitative RT-PCR .", "annotated_text": "<protein>NF-kappaB</protein> and <protein>activator protein-1</protein> ( <protein>AP-1</protein> ) activation were assessed by gel shift assay , and mRNA expression of <rna>interleukin-6</rna> , <protein>tumor necrosis factor-alpha</protein> , KC , <protein>monocyte chemoattractant protein-1</protein> , and <protein>inducible nitric oxide synthase</protein> was assessed by semiquantitative RT-PCR ."}
{"id": "2124", "text": "Morphological damage and trypsin activation were much greater in the pancreatic head than tail , in parallel with a stronger activation of NF-kappaB and cytokine mRNA .", "annotated_text": "Morphological damage and trypsin activation were much greater in the pancreatic head than tail , in parallel with a stronger activation of <rna>NF-kappaB and cytokine mRNA</rna> ."}
{"id": "2125", "text": "Saline infusion mildly affected these parameters .", "annotated_text": "Saline infusion mildly affected these parameters ."}
{"id": "2126", "text": "AP-1 was strongly activated in both pancreatic segments after either taurocholate or saline infusion .", "annotated_text": "<protein>AP-1</protein> was strongly activated in both pancreatic segments after either taurocholate or saline infusion ."}
{"id": "2127", "text": "NF-kappaB inhibition with N-acetylcysteine ameliorated the local inflammatory response .", "annotated_text": "<protein>NF-kappaB</protein> inhibition with N-acetylcysteine ameliorated the local inflammatory response ."}
{"id": "2128", "text": "Correlation between localized NF-kappaB activation , cytokine upregulation , and tissue damage suggests a key role for NF-kappaB in the development of the inflammatory response of acute pancreatitis .", "annotated_text": "Correlation between localized <protein>NF-kappaB</protein> activation , cytokine upregulation , and tissue damage suggests a key role for <protein>NF-kappaB</protein> in the development of the inflammatory response of acute pancreatitis ."}
{"id": "2129", "text": "CD45 tyrosine phosphatase controls common gamma-chain cytokine -mediated STAT and extracellular signal-related kinase phosphorylation in activated human lymphoblasts : inhibition of proliferation without induction of apoptosis .", "annotated_text": "<protein>CD45 tyrosine phosphatase</protein> controls common <protein>gamma-chain cytokine</protein> -mediated <protein>STAT</protein> and extracellular signal-related kinase phosphorylation in <cell_type>activated human lymphoblasts</cell_type> : inhibition of proliferation without induction of apoptosis ."}
{"id": "2130", "text": "The objective of this study was to test whether CD45 signals can influence signaling processes in activated human lymphoblasts .", "annotated_text": "The objective of this study was to test whether CD45 signals can influence signaling processes in <cell_type>activated human lymphoblasts</cell_type> ."}
{"id": "2131", "text": "To this end , we generated lymphoblasts which proliferate in response to common gamma-chain cytokines , but readily undergo apoptosis after cytokine withdrawal .", "annotated_text": "To this end , we generated <cell_type>lymphoblasts</cell_type> which proliferate in response to common <protein>gamma-chain cytokines</protein> , but readily undergo apoptosis after cytokine withdrawal ."}
{"id": "2132", "text": "In experiments with the CD45R0 mAb UCHL-1 , but not control CD45 mAbs , we found significant inhibition of proliferation .", "annotated_text": "In experiments with the <protein>CD45R0 mAb UCHL-1</protein> , but not <protein>control CD45 mAbs</protein> , we found significant inhibition of proliferation ."}
{"id": "2133", "text": "Interestingly , the pan-CD45 mAb GAP8.3 , which is most effective in inhibition of OKT-3-mediated proliferation in quiescent lymphocytes , was ineffective in lymphoblasts .", "annotated_text": "Interestingly , the <protein>pan-CD45 mAb GAP8.3</protein> , which is most effective in inhibition of OKT-3-mediated proliferation in <cell_type>quiescent lymphocytes</cell_type> , was ineffective in <cell_type>lymphoblasts</cell_type> ."}
{"id": "2134", "text": "Addition of CD3 mAb OKT-3 had no influence on IL-2-mediated proliferation ( with or without UCHL-1 ) .", "annotated_text": "Addition of <protein>CD3 mAb OKT-3</protein> had no influence on IL-2-mediated proliferation ( with or without <protein>UCHL-1</protein> ) ."}
{"id": "2135", "text": "In contrast , after addition of OKT-3 to IL-4 - and IL-7 -stimulated proliferation assays , UCHL-1 signals could not significantly alter cellular proliferation .", "annotated_text": "In contrast , after addition of <protein>OKT-3</protein> to <protein>IL-4</protein> - and <protein>IL-7</protein> -stimulated proliferation assays , <protein>UCHL-1</protein> signals could not significantly alter cellular proliferation ."}
{"id": "2136", "text": "We did not find induction of apoptosis following CD45R0 signaling .", "annotated_text": "We did not find induction of apoptosis following CD45R0 signaling ."}
{"id": "2137", "text": "In Western blots using mAbs detecting phosphorylated STAT-3 , STAT-5 , STAT-6 , or extracellular signal-related kinase 1/2 , we found that CD45R0 signaling could effectively diminish phosphorylation of these intracellular signaling components .", "annotated_text": "In Western blots using <protein>mAbs</protein> detecting <protein>phosphorylated STAT-3 , STAT-5 , STAT-6</protein> , or <protein>extracellular signal-related kinase 1/2</protein> , we found that CD45R0 signaling could effectively diminish phosphorylation of these intracellular signaling components ."}
{"id": "2138", "text": "Using RT-PCR , we found that CD45R0 signaling inhibited IL-2 mRNA production without major influence on IL-13 , IL-5 , or IFN-gamma mRNA levels .", "annotated_text": "Using RT-PCR , we found that CD45R0 signaling inhibited IL-2 mRNA production without major influence on <protein>IL-13</protein> , <protein>IL-5</protein> , or <rna>IFN-gamma mRNA</rna> levels ."}
{"id": "2139", "text": "Costimulation with OKT-3 and IL-2 optimally induced secretion of IFN-gamma , TNF-alpha , and IL-5 , which was not decreased by CD45 signals .", "annotated_text": "Costimulation with <protein>OKT-3</protein> and <protein>IL-2</protein> optimally induced secretion of <protein>IFN-gamma</protein> , <protein>TNF-alpha</protein> , and <protein>IL-5</protein> , which was not decreased by CD45 signals ."}
{"id": "2140", "text": "In conclusion , we illustrate that CD45R0 signals control early cytokine receptor-associated signaling processes and mRNA and DNA synthesis in activated human lymphoblasts .", "annotated_text": "In conclusion , we illustrate that CD45R0 signals control early cytokine receptor-associated signaling processes and mRNA and DNA synthesis in <cell_type>activated human lymphoblasts</cell_type> ."}
{"id": "2141", "text": "Furthermore , we show the existence of CD45 epitopes ( GAP8.3 ) , which are active and critical for signaling in quiescent lymphocytes , but are nonfunctional in activated human lymphoblasts .", "annotated_text": "Furthermore , we show the existence of <protein>CD45 epitopes</protein> ( <protein>GAP8.3</protein> ) , which are active and critical for signaling in <cell_type>quiescent lymphocytes</cell_type> , but are nonfunctional in <cell_type>activated human lymphoblasts</cell_type> ."}
{"id": "2142", "text": "Pax5 determines the identity of B cells from the beginning to the end of B-lymphopoiesis .", "annotated_text": "<dna>Pax5</dna> determines the identity of <cell_type>B cells</cell_type> from the beginning to the end of B-lymphopoiesis ."}
{"id": "2143", "text": "Despite being one of the most intensively studied cell types , the molecular basis of B cell specification is largely unknown .", "annotated_text": "Despite being one of the most intensively studied cell types , the molecular basis of B cell specification is largely unknown ."}
{"id": "2144", "text": "The Pax5 gene encoding the transcription factor BSAP is required for progression of B-lymphopoiesis beyond the pro-B cell stage .", "annotated_text": "The <dna>Pax5 gene</dna> encoding the <protein>transcription factor BSAP</protein> is required for progression of B-lymphopoiesis beyond the pro-B cell stage ."}
{"id": "2145", "text": "Pax5-deficient pro-B cells are , however , not yet committed to the B-lymphoid lineage , but instead have a broad lymphomyeloid developmental potential .", "annotated_text": "<cell_type>Pax5-deficient pro-B cells</cell_type> are , however , not yet committed to the <cell_type>B-lymphoid lineage</cell_type> , but instead have a broad lymphomyeloid developmental potential ."}
{"id": "2146", "text": "Pax5 appears to mediate B-lineage commitment by repressing the transcription of non-B-lymphoid genes and by simultaneously activating the expression of B-lineage-specific genes .", "annotated_text": "<dna>Pax5</dna> appears to mediate B-lineage commitment by repressing the transcription of <dna>non-B-lymphoid genes</dna> and by simultaneously activating the expression of <dna>B-lineage-specific genes</dna> ."}
{"id": "2147", "text": "Pax5 thus functions both as a transcriptional repressor and activator , depending on its interactions with corepressors of the Groucho protein family or with positive regulators such as the TATA-binding protein .", "annotated_text": "<dna>Pax5</dna> thus functions both as a transcriptional repressor and activator , depending on its interactions with <protein>corepressors</protein> of the <protein>Groucho protein family</protein> or with positive regulators such as the <protein>TATA-binding protein</protein> ."}
{"id": "2148", "text": "Once committed to the B-lineage , B cells require Pax5 function to maintain their B-lymphoid identity throughout B cell development", "annotated_text": "Once committed to the <cell_type>B-lineage</cell_type> , <cell_type>B cells</cell_type> require <dna>Pax5</dna> function to maintain their B-lymphoid identity throughout B cell development"}
{"id": "2149", "text": "Partners in transcription : NFAT and AP-1 .", "annotated_text": "Partners in transcription : <protein>NFAT</protein> and <protein>AP-1</protein> ."}
{"id": "2150", "text": "Combinatorial regulation is a powerful mechanism that enables tight control of gene expression , via integration of multiple signaling pathways that induce different transcription factors required for enhanceosome assembly .", "annotated_text": "Combinatorial regulation is a powerful mechanism that enables tight control of gene expression , via integration of multiple signaling pathways that induce different <protein>transcription factors</protein> required for enhanceosome assembly ."}
{"id": "2151", "text": "The four calcium-regulated transcription factors of the NFAT family act synergistically with AP-1 ( Fos/Jun ) proteins on composite DNA elements which contain adjacent NFAT and AP-1 binding sites , where they form highly stable ternary complexes to regulate the expression of diverse inducible genes .", "annotated_text": "The four calcium-regulated <protein>transcription factors</protein> of the <protein>NFAT family</protein> act synergistically with <protein>AP-1 ( Fos/Jun ) proteins</protein> on composite DNA elements which contain adjacent <dna>NFAT and AP-1 binding sites</dna> , where they form highly stable ternary complexes to regulate the expression of diverse inducible genes ."}
{"id": "2152", "text": "Concomitant induction of NFAT and AP-1 requires concerted activation of two different signaling pathways : calcium/calcineurin , which promotes NFAT dephosphorylation , nuclear translocation and activation ; and protein kinase C ( PKC ) /Ras , which promotes the synthesis , phosphorylation and activation of members of the Fos and Jun families of transcription factors .", "annotated_text": "Concomitant induction of <protein>NFAT</protein> and <protein>AP-1</protein> requires concerted activation of two different signaling pathways : calcium/calcineurin , which promotes NFAT dephosphorylation , nuclear translocation and activation ; and <protein>protein kinase C ( PKC ) /Ras</protein> , which promotes the synthesis , phosphorylation and activation of members of the <protein>Fos and Jun families</protein> of <protein>transcription factors</protein> ."}
{"id": "2153", "text": "A fifth member of the NFAT family , NFAT5 , controls the cellular response to osmotic stress , by a mechanism that requires dimer formation and is independent of calcineurin or of interaction with AP-1 .", "annotated_text": "A fifth member of the <protein>NFAT family</protein> , <protein>NFAT5</protein> , controls the cellular response to osmotic stress , by a mechanism that requires dimer formation and is independent of <protein>calcineurin</protein> or of interaction with <protein>AP-1</protein> ."}
{"id": "2154", "text": "Pharmacological interference with theNFAT : AP-1 interaction may be useful in selective manipulation of the immune response .", "annotated_text": "Pharmacological interference with theNFAT : AP-1 interaction may be useful in selective manipulation of the immune response ."}
{"id": "2155", "text": "Balanced activation of NFAT and AP-1 is known to be required for productive immune responses , but the role of NFAT : AP-1 interactions in other cell types and biological processes remains to be understood .", "annotated_text": "Balanced activation of <protein>NFAT</protein> and <protein>AP-1</protein> is known to be required for productive immune responses , but the role of NFAT : AP-1 interactions in other cell types and biological processes remains to be understood ."}
{"id": "2156", "text": "Cytokine production by Vgamma ( + ) -T-cell subsets is an important factor determining CD4 ( + ) -Th-cell phenotype and susceptibility of BALB/c mice to coxsackievirus B3-induced myocarditis .", "annotated_text": "Cytokine production by <cell_type>Vgamma ( + ) -T-cell subsets</cell_type> is an important factor determining CD4 ( + ) -Th-cell phenotype and susceptibility of BALB/c mice to coxsackievirus B3-induced myocarditis ."}
{"id": "2157", "text": "Two coxsackievirus B3 ( CVB3 ) variants ( H3 and H310A1 ) differ by a single amino acid mutation in the VP2 capsid protein .", "annotated_text": "Two coxsackievirus B3 ( CVB3 ) variants ( H3 and H310A1 ) differ by a single amino acid mutation in the <protein>VP2 capsid protein</protein> ."}
{"id": "2158", "text": "H3 induces severe myocarditis in BALB/c mice , but H310A1 is amyocarditic .", "annotated_text": "H3 induces severe myocarditis in BALB/c mice , but H310A1 is amyocarditic ."}
{"id": "2159", "text": "Infection with H3 , but not H310A1 , preferentially activates Vgamma4 Vdelta4 cells , which are strongly positive for gamma interferon ( IFN-gamma ) , whereas Vgamma1 Vdelta4 cells are increased in both H3 and H310A1 virus-infected animals .", "annotated_text": "Infection with H3 , but not H310A1 , preferentially activates <cell_type>Vgamma4 Vdelta4 cells</cell_type> , which are strongly positive for <protein>gamma interferon</protein> ( <protein>IFN-gamma</protein> ) , whereas <cell_type>Vgamma1 Vdelta4 cells</cell_type> are increased in both H3 and H310A1 virus-infected animals ."}
{"id": "2160", "text": "Depletion of Vgamma1 ( + ) cells using monoclonal anti-Vgamma1 antibody enhanced myocarditis and CD4 ( + ) - , IFN-gamma ( + ) -cell responses in both H3- and H310A1-infected mice yet decreased the CD4 ( + ) - , IL-4 ( + ) -cell response .", "annotated_text": "Depletion of <cell_type>Vgamma1 ( + ) cells</cell_type> using <protein>monoclonal anti-Vgamma1 antibody</protein> enhanced myocarditis and CD4 ( + ) - , <protein>IFN-gamma</protein> ( + ) -cell responses in both H3- and H310A1-infected mice yet decreased the CD4 ( + ) - , IL-4 ( + ) -cell response ."}
{"id": "2161", "text": "Depleting Vgamma4 ( + ) cells suppressed myocarditis and reduced CD4 ( + ) IFN-gamma ( + ) cells but increased CD4 ( + ) IL-4 ( + ) T cells .", "annotated_text": "Depleting <cell_type>Vgamma4 ( + ) cells</cell_type> suppressed myocarditis and reduced <cell_type>CD4 ( + ) IFN-gamma ( + ) cells</cell_type> but increased <cell_type>CD4 ( + ) IL-4 ( + ) T cells</cell_type> ."}
{"id": "2162", "text": "The role of cytokine production by Vgamma1 ( + ) and Vgamma4 ( + ) T cells was investigated by adoptively transferring these cells isolated from H3-infected BALB/c Stat4 knockout ( Stat4ko ) ( defective in IFN-gamma expression ) or BALB/c Stat6ko ( defective in IL-4 expression ) mice into H3 virus-infected wild-type BALB/c recipients .", "annotated_text": "The role of cytokine production by <cell_type>Vgamma1 ( + ) and Vgamma4 ( + ) T cells</cell_type> was investigated by adoptively transferring these cells isolated from H3-infected BALB/c Stat4 knockout ( Stat4ko ) ( defective in <protein>IFN-gamma</protein> expression ) or BALB/c Stat6ko ( defective in IL-4 expression ) mice into H3 virus-infected wild-type BALB/c recipients ."}
{"id": "2163", "text": "Vgamma4 and Vgamma1 ( + ) T cells from Stat4ko mice expressed IL-4 but no or minimal IFN-gamma , whereas these cell populations derived from Stat6ko mice expressed IFN-gamma but no IL-4 .", "annotated_text": "<cell_type>Vgamma4 and Vgamma1 ( + ) T cells</cell_type> from Stat4ko mice expressed <protein>IL-4</protein> but no or minimal <protein>IFN-gamma</protein> , whereas these cell populations derived from Stat6ko mice expressed <protein>IFN-gamma</protein> but no <protein>IL-4</protein> ."}
{"id": "2164", "text": "Stat4ko Vgamma1 ( + ) cells ( IL-4 ( + ) ) suppress myocarditis .", "annotated_text": "<cell_type>Stat4ko Vgamma1 ( + ) cells ( IL-4 ( + )</cell_type> ) suppress myocarditis ."}
{"id": "2165", "text": "Stat6ko Vgamma1 ( + ) cells ( IFN-gamma ( + ) ) were not inhibitory .", "annotated_text": "<cell_type>Stat6ko Vgamma1 ( + ) cells ( IFN-gamma ( + ) )</cell_type> were not inhibitory ."}
{"id": "2166", "text": "Stat6ko Vgamma4 ( + ) cells ( IFN-gamma ( + ) ) significantly enhanced myocarditis .", "annotated_text": "<cell_type>Stat6ko Vgamma4 ( + ) cells ( IFN-gamma ( + ) )</cell_type> significantly enhanced myocarditis ."}
{"id": "2167", "text": "Stat4ko Vgamma4 ( + ) cells ( IL-4 ( + ) ) neither inhibited nor enhanced disease .", "annotated_text": "<cell_type>Stat4ko Vgamma4 ( + ) cells ( IL-4 ( + ) )</cell_type> neither inhibited nor enhanced disease ."}
{"id": "2168", "text": "These results show that distinct gammadelta-T-cell subsets control myocarditis susceptibility and bias the CD4 ( + ) -Th-cell response .", "annotated_text": "These results show that distinct <cell_type>gammadelta-T-cell subsets</cell_type> control myocarditis susceptibility and bias the <cell_type>CD4 ( + ) -Th-cell</cell_type> response ."}
{"id": "2169", "text": "The cytokines produced by the Vgamma subpopulation have a significant influence on the CD4 ( + ) -Th-cell phenotype .", "annotated_text": "The <protein>cytokines</protein> produced by the <cell_type>Vgamma subpopulation</cell_type> have a significant influence on the <protein>CD4</protein> ( + ) -Th-cell phenotype ."}
{"id": "2170", "text": "Plasmin -induced expression of cytokines and tissue factor in human monocytes involves AP-1 and IKKbeta -mediated NF-kappaB activation .", "annotated_text": "<protein>Plasmin</protein> -induced expression of <protein>cytokines</protein> and <protein>tissue factor</protein> in <cell_type>human monocytes</cell_type> involves <protein>AP-1</protein> and <protein>IKKbeta</protein> -mediated NF-kappaB activation ."}
{"id": "2171", "text": "It was previously shown that plasmin activates human peripheral monocytes in terms of lipid mediator release and chemotactic migration .", "annotated_text": "It was previously shown that <protein>plasmin</protein> activates <cell_type>human peripheral monocytes</cell_type> in terms of lipid mediator release and chemotactic migration ."}
{"id": "2172", "text": "Here it is demonstrated that plasmin induces proinflammatory cytokine release and tissue factor ( TF ) expression by monocytes .", "annotated_text": "Here it is demonstrated that <protein>plasmin</protein> induces <protein>proinflammatory cytokine</protein> release and <protein>tissue factor</protein> ( <protein>TF</protein> ) expression by <cell_type>monocytes</cell_type> ."}
{"id": "2173", "text": "Plasmin 0.043 to 1.43 CTA U/mL , but not active site-blocked plasmin , triggered concentration-dependent expression of mRNA for interleukin-1alpha ( IL-1alpha ) , IL-1beta , tumor necrosis factor-alpha ( TNF-alpha ) , and TF with maximum responses after 4 hours .", "annotated_text": "<protein>Plasmin</protein> 0.043 to 1.43 CTA U/mL , but not <protein>active site-blocked plasmin</protein> , triggered concentration-dependent expression of mRNA for <protein>interleukin-1alpha</protein> ( <protein>IL-1alpha</protein> ) , <protein>IL-1beta</protein> , <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) , and <protein>TF</protein> with maximum responses after 4 hours ."}
{"id": "2174", "text": "Plasmin -mediated mRNA expression was inhibited in a concentration-dependent manner by the lysine analogue trans-4- ( aminomethyl ) cyclohexane-1-carboxylic acid ( t-AMCA ) .", "annotated_text": "<protein>Plasmin</protein> -mediated mRNA expression was inhibited in a concentration-dependent manner by the lysine analogue trans-4- ( aminomethyl ) cyclohexane-1-carboxylic acid ( t-AMCA ) ."}
{"id": "2175", "text": "Increases in mRNA levels were followed by concentration- and time-dependent release of IL-1alpha , IL-1beta and TNF-alpha and by TF expression on monocyte surfaces .", "annotated_text": "Increases in mRNA levels were followed by concentration- and time-dependent release of <protein>IL-1alpha</protein> , <protein>IL-1beta</protein> and <protein>TNF-alpha</protein> and by <protein>TF</protein> expression on monocyte surfaces ."}
{"id": "2176", "text": "Neither cytokines nor TF could be detected when monocytes were preincubated with actinomycin D or cycloheximide .", "annotated_text": "Neither <protein>cytokines</protein> nor <protein>TF</protein> could be detected when <cell_type>monocytes</cell_type> were preincubated with actinomycin D or cycloheximide ."}
{"id": "2177", "text": "Electrophoretic mobility shift assays indicated plasmin -induced activation of NF-kappaB ; DNA-binding complexes were composed of p50 , p65 , and c-Rel , as shown by supershift experiments .", "annotated_text": "Electrophoretic mobility shift assays indicated <protein>plasmin</protein> -induced activation of <protein>NF-kappaB</protein> ; <protein>DNA-binding complexes</protein> were composed of <protein>p50</protein> , <protein>p65</protein> , and <protein>c-Rel</protein> , as shown by supershift experiments ."}
{"id": "2178", "text": "Nuclear translocation of NF-kappaB/Rel proteins coincided with IkappaBalpha degradation .", "annotated_text": "Nuclear translocation of <protein>NF-kappaB/Rel proteins</protein> coincided with IkappaBalpha degradation ."}
{"id": "2179", "text": "At variance with endotoxic lipopolysaccharide , plasmin elicited the rapid degradation of another cytoplasmic NF-kappaB inhibitor , p105 .", "annotated_text": "At variance with endotoxic lipopolysaccharide , <protein>plasmin</protein> elicited the rapid degradation of another <protein>cytoplasmic NF-kappaB inhibitor , p105</protein> ."}
{"id": "2180", "text": "Proteolysis of NF-kappaB inhibitors was apparently due to transient activation of IkappaB kinase ( IKK ) beta that reached maximum activity at 1 hour after plasmin stimulation .", "annotated_text": "Proteolysis of NF-kappaB inhibitors was apparently due to transient activation of <protein>IkappaB kinase ( IKK ) beta</protein> that reached maximum activity at 1 hour after <protein>plasmin</protein> stimulation ."}
{"id": "2181", "text": "In addition , AP-1 binding was increased in plasmin -treated monocytes , with most complexes composed of JunD , c-Fos , and FosB .", "annotated_text": "In addition , AP-1 binding was increased in <protein>plasmin</protein> -treated <cell_type>monocytes</cell_type> , with most complexes composed of <protein>JunD</protein> , <protein>c-Fos</protein> , and <protein>FosB</protein> ."}
{"id": "2182", "text": "These findings further substantiate the role of plasmin as a proinflammatory activator of human monocytes and reveal an important new link between the plasminogen-plasmin system and inflammation .", "annotated_text": "These findings further substantiate the role of <protein>plasmin</protein> as a proinflammatory activator of <cell_type>human monocytes</cell_type> and reveal an important new link between the plasminogen-plasmin system and inflammation ."}
{"id": "2183", "text": "( Blood. 2001 ; 97 : 3941-3950 )", "annotated_text": "( Blood. 2001 ; 97 : 3941-3950 )"}
{"id": "2184", "text": "STAT3 is constitutively active in some patients with Polycythemia rubra vera .", "annotated_text": "<protein>STAT3</protein> is constitutively active in some patients with Polycythemia rubra vera ."}
{"id": "2185", "text": "OBJECTIVE : Polycythemia vera is a clonal stem cell disorder characterized by hyperproliferation of the erythroid , myeloid , and megakaryocytic lineages .", "annotated_text": "OBJECTIVE : Polycythemia vera is a clonal stem cell disorder characterized by hyperproliferation of the <cell_type>erythroid , myeloid , and megakaryocytic lineages</cell_type> ."}
{"id": "2186", "text": "While it has been shown that progenitor cells of P. vera patients are hypersensitive to several growth factors including erythropoietin , insulin-like growth factor-1 , thrombopoietin , interleukin-3 , and granulocyte/monocyte colony-stimulating factor , the molecular pathogenesis of this disease remains unknown .", "annotated_text": "While it has been shown that <cell_type>progenitor cells</cell_type> of P. vera patients are hypersensitive to several growth factors including <protein>erythropoietin</protein> , <protein>insulin-like growth factor-1</protein> , <protein>thrombopoietin</protein> , <protein>interleukin-3</protein> , and <protein>granulocyte/monocyte colony-stimulating factor</protein> , the molecular pathogenesis of this disease remains unknown ."}
{"id": "2187", "text": "Growth factor hypersensitivity could be mediated by changes in signal transduction pathways .", "annotated_text": "Growth factor hypersensitivity could be mediated by changes in signal transduction pathways ."}
{"id": "2188", "text": "We therefore investigated a common downstream effector of cytokines , the signal transducers and activators of transcription ( STATs ) .", "annotated_text": "We therefore investigated a common downstream effector of <protein>cytokines</protein> , the <protein>signal transducers and activators of transcription</protein> ( <protein>STATs</protein> ) ."}
{"id": "2189", "text": "A constitutive activation of STAT factors could explain the increased proliferation of P. vera cells even in the absence of growth factor stimulation .", "annotated_text": "A constitutive activation of <protein>STAT factors</protein> could explain the increased proliferation of <cell_type>P. vera cells</cell_type> even in the absence of growth factor stimulation ."}
{"id": "2190", "text": "METHODS : Peripheral granulocytes from patients with P. vera and from healthy volunteers were assayed for STAT1 , 3 , and 5 DNA binding by electrophoretic mobility shift assay .", "annotated_text": "METHODS : <cell_type>Peripheral granulocytes</cell_type> from patients with P. vera and from healthy volunteers were assayed for <protein>STAT1 , 3 , and 5</protein> DNA binding by electrophoretic mobility shift assay ."}
{"id": "2191", "text": "RESULTS : Four of 14 P. vera patients analyzed showed constitutive STAT3 DNA binding in unstimulated peripheral granulocytes , while none of the 17 healthy volunteers tested did .", "annotated_text": "RESULTS : Four of 14 P. vera patients analyzed showed constitutive STAT3 DNA binding in <cell_type>unstimulated peripheral granulocytes</cell_type> , while none of the 17 healthy volunteers tested did ."}
{"id": "2192", "text": "of the subjects showed constitutive STAT1 or STAT5 activity .", "annotated_text": "of the subjects showed constitutive <protein>STAT1</protein> or <protein>STAT5</protein> activity ."}
{"id": "2193", "text": "Western blotting demonstrated that , in the three patients , STAT3 is constitutively phosphorylated on Tyr 705 , whereas it is unphosphorylated in the other patients and in controls .", "annotated_text": "Western blotting demonstrated that , in the three patients , <protein>STAT3</protein> is constitutively phosphorylated on Tyr 705 , whereas it is unphosphorylated in the other patients and in controls ."}
{"id": "2194", "text": "Interestingly , constitutive STAT3 activity did not correlate with the duration of disease or the treatment regimen .", "annotated_text": "Interestingly , constitutive <protein>STAT3</protein> activity did not correlate with the duration of disease or the treatment regimen ."}
{"id": "2195", "text": "It was observed in a recently diagnosed patient and in two patients treated only with phlebotomy .", "annotated_text": "It was observed in a recently diagnosed patient and in two patients treated only with phlebotomy ."}
{"id": "2196", "text": "CONCLUSION : Our data suggest that constitutive phosphorylation and activation of STAT3 is not a secondary event induced by mutagenizing agents or by prolonged hyperproliferation of hematopoietic cells , but rather represents a primary molecular aberration .", "annotated_text": "CONCLUSION : Our data suggest that constitutive phosphorylation and activation of <protein>STAT3</protein> is not a secondary event induced by mutagenizing agents or by prolonged hyperproliferation of <cell_type>hematopoietic cells</cell_type> , but rather represents a primary molecular aberration ."}
{"id": "2197", "text": "Constitutively active STAT3 may contribute to the growth factor hypersensitivity of P. vera cells .", "annotated_text": "<protein>Constitutively active STAT3</protein> may contribute to the growth factor hypersensitivity of <cell_type>P. vera cells</cell_type> ."}
{"id": "2198", "text": "Identification of phosphorylation sites for Bruton 's tyrosine kinase within the transcriptional regulator BAP/TFII-I .", "annotated_text": "Identification of <protein>phosphorylation sites</protein> for <protein>Bruton 's tyrosine kinase</protein> within the <protein>transcriptional regulator BAP/TFII-I</protein> ."}
{"id": "2199", "text": "Bruton 's tyrosine kinase ( Btk ) , a member of the Tec family of cytosolic kinases , is essential for B cell development and function .", "annotated_text": "<protein>Bruton 's tyrosine kinase</protein> ( <protein>Btk</protein> ) , a member of the <protein>Tec family of cytosolic kinases</protein> , is essential for <cell_type>B cell</cell_type> development and function ."}
{"id": "2200", "text": "BAP/TFII-I , a protein implicated in transcriptional regulation , is associated with Btk in B cells and is transiently phosphorylated on tyrosine following B cell receptor engagement .", "annotated_text": "<protein>BAP/TFII-I</protein> , a protein implicated in transcriptional regulation , is associated with <protein>Btk</protein> in <cell_type>B cells</cell_type> and is transiently phosphorylated on tyrosine following <cell_type>B cell</cell_type> receptor engagement ."}
{"id": "2201", "text": "BAP/TFII-I is a substrate for Btk in vitro and is hyperphosphorylated on tyrosine upon coexpression with Btk in mammalian cells .", "annotated_text": "<protein>BAP/TFII-I</protein> is a substrate for <protein>Btk</protein> in vitro and is hyperphosphorylated on tyrosine upon coexpression with <protein>Btk</protein> in <cell_type>mammalian cells</cell_type> ."}
{"id": "2202", "text": "In an effort to understand the physiologic consequences of BAP/TFII-I tyrosine phosphorylation following B cell receptor stimulation , site-directed mutagenesis and phosphopeptide mapping were used to locate the predominant sites of BAP/TFII-I phosphorylation by Btk in vitro .", "annotated_text": "In an effort to understand the physiologic consequences of <protein>BAP/TFII-I</protein> tyrosine phosphorylation following B cell receptor stimulation , site-directed mutagenesis and phosphopeptide mapping were used to locate the predominant sites of <protein>BAP/TFII-I</protein> phosphorylation by <protein>Btk</protein> in vitro ."}
{"id": "2203", "text": "These residues , Tyr248 , Tyr357 , and Tyr462 , were also found to be the major sites for Btk -dependent phosphorylation of BAP/TFII-I in vivo .", "annotated_text": "These residues , Tyr248 , Tyr357 , and Tyr462 , were also found to be the major sites for <protein>Btk</protein> -dependent phosphorylation of <protein>BAP/TFII-I</protein> in vivo ."}
{"id": "2204", "text": "Residues Tyr357 and Tyr462 are contained within the loop regions of adjacent helix-loop-helix-like repeats within BAP/TFII-I .", "annotated_text": "Residues Tyr357 and Tyr462 are contained within the <protein>loop regions</protein> of adjacent <protein>helix-loop-helix-like repeats</protein> within <protein>BAP/TFII-I</protein> ."}
{"id": "2205", "text": "Mutation of either Tyr248 , Tyr357 , or Tyr462 to phenylalanine reduced transcription from a c-fos promoter relative to wild-type BAP/TFII-I in transfected COS-7 cells , consistent with the interpretation that phosphorylation at these sites contributes to transcriptional activation .", "annotated_text": "Mutation of either Tyr248 , Tyr357 , or Tyr462 to phenylalanine reduced transcription from a <dna>c-fos promoter</dna> relative to <dna>wild-type BAP/TFII-I</dna> in transfected <cell_line>COS-7 cells</cell_line> , consistent with the interpretation that phosphorylation at these sites contributes to transcriptional activation ."}
{"id": "2206", "text": "Phosphorylation of BAP/TFII-I by Btk may link engagement of receptors such as surface immunoglobulin to modulation of gene expression .", "annotated_text": "Phosphorylation of <protein>BAP/TFII-I</protein> by <protein>Btk</protein> may link engagement of receptors such as surface <protein>immunoglobulin</protein> to modulation of gene expression ."}
{"id": "2207", "text": "Expression of interferon consensus sequence binding protein induces potent immunity against BCR/ABL-induced leukemia .", "annotated_text": "Expression of <protein>interferon consensus sequence binding protein</protein> induces potent immunity against BCR/ABL-induced leukemia ."}
{"id": "2208", "text": "Mice deficient in the interferon consensus sequence binding protein ( ICSBP ) develop a disease resembling chronic myeloid leukemia ( CML ) , which in humans is caused by the BCR/ABL oncoprotein .", "annotated_text": "Mice deficient in the <protein>interferon consensus sequence binding protein</protein> ( <protein>ICSBP</protein> ) develop a disease resembling chronic myeloid leukemia ( CML ) , which in humans is caused by the <protein>BCR/ABL oncoprotein</protein> ."}
{"id": "2209", "text": "Interferon-alpha ( IFN-alpha ) induces ICSBP expression and is an effective therapy for CML .", "annotated_text": "<protein>Interferon-alpha</protein> ( <protein>IFN-alpha</protein> ) induces <protein>ICSBP</protein> expression and is an effective therapy for CML ."}
{"id": "2210", "text": "This study examined whether enforced expression of ICSBP might antagonize BCR/ABL-induced leukemia ; results demonstrated that ICSBP-modified cells generated a protective CD8 ( + ) cytotoxic T-cell response against BCR/ABL-transformed BaF3 cells in a murine leukemia model .", "annotated_text": "This study examined whether enforced expression of <protein>ICSBP</protein> might antagonize BCR/ABL-induced leukemia ; results demonstrated that <cell_type>ICSBP-modified cells</cell_type> generated a protective CD8 ( + ) cytotoxic T-cell response against <cell_type>BCR/ABL-transformed BaF3 cells</cell_type> in a murine leukemia model ."}
{"id": "2211", "text": "ICSBP expression represents a novel means of stimulating a host immune response to BCR/ABL ( + ) leukemia cells and a potential strategy for immunotherapy of CML .", "annotated_text": "<protein>ICSBP</protein> expression represents a novel means of stimulating a host immune response to <cell_type>BCR/ABL ( + ) leukemia cells</cell_type> and a potential strategy for immunotherapy of CML ."}
{"id": "2212", "text": "( Blood. 2001 ; 97 : 3491-3497 )", "annotated_text": "( Blood. 2001 ; 97 : 3491-3497 )"}
{"id": "2213", "text": "A transcriptional block in the IL-2 promoter at the -150 AP-1 site in effector CD8+ T cells .", "annotated_text": "A transcriptional block in the <dna>IL-2 promoter</dna> at the <dna>-150 AP-1 site</dna> in <cell_type>effector CD8+ T cells</cell_type> ."}
{"id": "2214", "text": "Both CD4+ and CD8+ T cells that produce IL-2 in response to Ag recognition have been isolated .", "annotated_text": "Both <cell_type>CD4+ and CD8+ T cells</cell_type> that produce <protein>IL-2</protein> in response to Ag recognition have been isolated ."}
{"id": "2215", "text": "However , most effector CD8+ T cells recovered after exposure to Ag do not produce sufficient IL-2 to sustain growth , and depend on CD4+ T helper cells for this obligate growth factor .", "annotated_text": "However , most <cell_type>effector CD8+ T cells</cell_type> recovered after exposure to <protein>Ag</protein> do not produce sufficient <protein>IL-2</protein> to sustain growth , and depend on <cell_type>CD4+ T helper cells</cell_type> for this obligate growth factor ."}
{"id": "2216", "text": "IL-2 expression in CD4+ T cells is primarily controlled at the level of transcription , but mechanisms restricting IL-2 production in CD8+ T cells have not been elucidated .", "annotated_text": "IL-2 expression in <cell_type>CD4+ T cells</cell_type> is primarily controlled at the level of transcription , but mechanisms restricting IL-2 production in <cell_type>CD8+ T cells</cell_type> have not been elucidated ."}
{"id": "2217", "text": "To evaluate transcriptional regulation of the IL-2 gene in CD8+ T cells , we stably transfected reporter genes into Ag -specific CD8+ T cell clones .", "annotated_text": "To evaluate transcriptional regulation of the <dna>IL-2 gene</dna> in <cell_type>CD8+ T cells</cell_type> , we stably transfected <dna>reporter genes</dna> into <protein>Ag</protein> -specific <cell_line>CD8+ T cell clones</cell_line> ."}
{"id": "2218", "text": "CD28+ CD8 ( + ) T cells unable to transcribe the IL-2 gene in response to antigenic stimulation had a block in transactivation of the -150 CD28 response element ( CD28RE ) /AP-1 site of the IL-2 promoter , but did transactivate the composite NFAT/AP-1 and OCT/AP-1 sites , and a consensus AP-1 motif .", "annotated_text": "<cell_type>CD28+ CD8 ( + ) T cells</cell_type> unable to transcribe the <dna>IL-2 gene</dna> in response to antigenic stimulation had a block in transactivation of the <dna>-150 CD28 response element ( CD28RE ) /AP-1 site</dna> of the <dna>IL-2 promoter</dna> , but did transactivate the composite <dna>NFAT/AP-1 and OCT/AP-1 sites</dna> , and a <dna>consensus AP-1 motif</dna> ."}
{"id": "2219", "text": "Mutation of the nonconsensus -150 AP-1 site to a consensus AP-1 site , or insertion of a CD28RE/AP-1 consensus site upstream of the native -150 CD28RE/AP-1 site restored transactivation of the altered promoter .", "annotated_text": "Mutation of the <dna>nonconsensus -150 AP-1 site</dna> to a <dna>consensus AP-1 site</dna> , or insertion of a <dna>CD28RE/AP-1 consensus site</dna> upstream of the native <dna>-150 CD28RE/AP-1 site</dna> restored transactivation of the altered <dna>promoter</dna> ."}
{"id": "2220", "text": "These results suggest that the defect at the -150 site may reflect the absence or inactivity of a required factor rather than repression of the IL-2 promoter .", "annotated_text": "These results suggest that the defect at the <dna>-150 site</dna> may reflect the absence or inactivity of a required factor rather than repression of the <dna>IL-2 promoter</dna> ."}
{"id": "2221", "text": "Stem cell factor and interleukin-3 induce stepwise generation of erythroid precursor cells from a basic fibroblast growth factor -dependent hematopoietic stem cell line , A-6 .", "annotated_text": "<protein>Stem cell factor</protein> and <protein>interleukin-3</protein> induce stepwise generation of <cell_type>erythroid precursor cells</cell_type> from a basic <protein>fibroblast growth factor</protein> -dependent <cell_line>hematopoietic stem cell line , A-6</cell_line> ."}
{"id": "2222", "text": "A m ultipotent immature myeloid cell population was produced from a basic fibroblast growth factor ( bFGF ) -dependent hematopoietic stem cell line , A-6 , when cultured with stem cell factor ( SCF ) replacing bFGF .", "annotated_text": "A m <cell_type>ultipotent immature myeloid cell population</cell_type> was produced from a <protein>basic fibroblast growth factor</protein> ( <protein>bFGF</protein> ) -dependent <cell_line>hematopoietic stem cell line , A-6</cell_line> , when cultured with <protein>stem cell factor</protein> ( <protein>SCF</protein> ) replacing <protein>bFGF</protein> ."}
{"id": "2223", "text": "Those cells were positive for stem cell markers , c-kit and CD34 , and a myeloid cell marker , F4/80 .", "annotated_text": "Those cells were positive for <protein>stem cell markers</protein> , <protein>c-kit</protein> and <protein>CD34</protein> , and a <protein>myeloid cell marker , F4/80</protein> ."}
{"id": "2224", "text": "Some cell fractions were also positive for Mac-1 , a macrophage marker or Gr-1 , a granulocytic maker , but negative for an erythroid marker TER119 .", "annotated_text": "Some cell fractions were also positive for <protein>Mac-1 , a macrophage marker</protein> or <protein>Gr-1 , a granulocytic maker</protein> , but negative for an <protein>erythroid marker TER119</protein> ."}
{"id": "2225", "text": "They also showed the expression of mRNA for the myeloid-specific PU.1 but did not that for the erythroid-specific GATA-1 .", "annotated_text": "They also showed the expression of mRNA for the <protein>myeloid-specific PU.1</protein> but did not that for the <protein>erythroid-specific GATA-1</protein> ."}
{"id": "2226", "text": "Among various cytokines , interleukin-3 ( IL-3 ) induced erythroid precursor cells that expressed the erythroid-specific GATA-1 and beta-major globin .", "annotated_text": "Among various <protein>cytokines</protein> , <protein>interleukin-3</protein> ( <protein>IL-3</protein> ) induced <cell_type>erythroid precursor cells</cell_type> that expressed the <protein>erythroid-specific GATA-1</protein> and <protein>beta-major globin</protein> ."}
{"id": "2227", "text": "The quantitative analysis showed that erythroid precursor cells were newly produced from the immature myeloid cells by cultivation with IL-3 .", "annotated_text": "The quantitative analysis showed that <cell_type>erythroid precursor cells</cell_type> were newly produced from the <cell_type>immature myeloid cells</cell_type> by cultivation with <protein>IL-3</protein> ."}
{"id": "2228", "text": "SCF and IL-3 induced stepwise generation of erythroid precursor cells from an A-6 hematopoietic stem cell line .", "annotated_text": "<protein>SCF</protein> and <protein>IL-3</protein> induced stepwise generation of <cell_type>erythroid precursor cells</cell_type> from an <cell_line>A-6 hematopoietic stem cell line</cell_line> ."}
{"id": "2229", "text": "Copyright 2001 Academic Press .", "annotated_text": "Copyright 2001 Academic Press ."}
{"id": "2230", "text": "Distinct BMI-1 and EZH2 expression patterns in thymocytes and mature T cells suggest a role for Polycomb genes in human T cell differentiation .", "annotated_text": "Distinct <protein>BMI-1</protein> and <protein>EZH2</protein> expression patterns in <cell_type>thymocytes</cell_type> and <cell_type>mature T cells</cell_type> suggest a role for <dna>Polycomb genes</dna> in human T cell differentiation ."}
{"id": "2231", "text": "BMI-1 and EZH2 Polycomb-group ( PcG ) proteins belong to two distinct protein complexes involved in the regulation of hematopoiesis .", "annotated_text": "<protein>BMI-1</protein> and <protein>EZH2</protein> <protein>Polycomb-group ( PcG ) proteins</protein> belong to two distinct protein complexes involved in the regulation of hematopoiesis ."}
{"id": "2232", "text": "Using unique PcG-specific antisera and triple immunofluorescence , we found that mature resting peripheral T cells expressed BMI-1 , whereas dividing blasts were EZH2 ( + ) .", "annotated_text": "Using unique PcG-specific antisera and triple immunofluorescence , we found that <cell_type>mature resting peripheral T cells</cell_type> expressed <protein>BMI-1</protein> , whereas <cell_type>dividing blasts</cell_type> were EZH2 ( + ) ."}
{"id": "2233", "text": "By contrast , subcapsular immature double-negative ( DN ) ( CD4 ( - ) /CD8 ( - ) ) T cells in the thymus coexpressed BMI-1 and EZH2 or were BMI-1 single positive .", "annotated_text": "By contrast , <cell_type>subcapsular immature double-negative ( DN ) ( CD4 ( - ) /CD8 ( - ) ) T cells</cell_type> in the thymus coexpressed <protein>BMI-1</protein> and <protein>EZH2</protein> or were BMI-1 single positive ."}
{"id": "2234", "text": "Their descendants , double-positive ( DP ; CD4 ( + ) /CD8 ( + ) ) cortical thymocytes , expressed EZH2 without BMI-1 .", "annotated_text": "Their descendants , <cell_type>double-positive ( DP ; CD4 ( + ) /CD8 ( + ) ) cortical thymocytes</cell_type> , expressed <protein>EZH2</protein> without <protein>BMI-1</protein> ."}
{"id": "2235", "text": "Most EZH2 ( + ) DN and DP thymocytes were dividing , while DN BMI-1 ( + ) /EZH2 ( - ) thymocytes were resting and proliferation was occasionally noted in DN BMI-1 ( + ) /EZH2 ( + ) cells .", "annotated_text": "Most <cell_type>EZH2 ( + ) DN and DP thymocytes</cell_type> were dividing , while <cell_type>DN BMI-1 ( + ) /EZH2 ( - ) thymocytes</cell_type> were resting and proliferation was occasionally noted in <cell_type>DN BMI-1 ( + ) /EZH2 ( + ) cells</cell_type> ."}
{"id": "2236", "text": "Maturation of DP cortical thymocytes to single-positive ( CD4 ( + ) /CD8 ( - ) or CD8 ( + ) /CD4 ( - ) ) medullar thymocytes correlated with decreased detectability of EZH2 and continued relative absence of BMI-1 .", "annotated_text": "Maturation of <cell_type>DP cortical thymocytes</cell_type> to <cell_type>single-positive ( CD4 ( + ) /CD8 ( - )</cell_type> or <cell_type>CD8 ( + ) /CD4 ( - ) ) medullar thymocytes</cell_type> correlated with decreased detectability of <protein>EZH2</protein> and continued relative absence of <protein>BMI-1</protein> ."}
{"id": "2237", "text": "Our data show that BMI-1 and EZH2 expression in mature peripheral T cells is mutually exclusive and linked to proliferation status , and that this pattern is not yet established in thymocytes of the cortex and medulla .", "annotated_text": "Our data show that <protein>BMI-1</protein> and <protein>EZH2</protein> expression in <cell_type>mature peripheral T cells</cell_type> is mutually exclusive and linked to proliferation status , and that this pattern is not yet established in <cell_type>thymocytes</cell_type> of the cortex and medulla ."}
{"id": "2238", "text": "T cell stage-specific PcG expression profiles suggest that PcG genes contribute to regulation of T cell differentiation .", "annotated_text": "<cell_type>T cell</cell_type> stage-specific PcG expression profiles suggest that <dna>PcG genes</dna> contribute to regulation of T cell differentiation ."}
{"id": "2239", "text": "They probably reflect stabilization of cell type-specific gene expression and irreversibility of lineage choice .", "annotated_text": "They probably reflect stabilization of cell type-specific gene expression and irreversibility of lineage choice ."}
{"id": "2240", "text": "The difference in PcG expression between medullar thymocytes and mature interfollicular T cells indicates that additional maturation processes occur after thymocyte transportation from the thymus .", "annotated_text": "The difference in PcG expression between <cell_type>medullar thymocytes</cell_type> and <cell_type>mature interfollicular T cells</cell_type> indicates that additional maturation processes occur after thymocyte transportation from the thymus ."}
{"id": "2241", "text": "Stepwise lineage restriction of progenitors in lympho-myelopoiesis .", "annotated_text": "Stepwise lineage restriction of <cell_type>progenitors</cell_type> in lympho-myelopoiesis ."}
{"id": "2242", "text": "It has long been controversial whether hematopoiesis progresses through ordered stages of determination as in embryonic development .", "annotated_text": "It has long been controversial whether hematopoiesis progresses through ordered stages of determination as in embryonic development ."}
{"id": "2243", "text": "This is due to the absence of a methodology capable of exactly determining the developmental potential of hematopoietic stem/progenitor cells .", "annotated_text": "This is due to the absence of a methodology capable of exactly determining the developmental potential of <cell_type>hematopoietic stem/progenitor cells</cell_type> ."}
{"id": "2244", "text": "The multilineage progenitor ( MLP ) assay enabled us to discriminate among seven types of hematopoietic progenitors , which are multipotent progenitor p-MTB ( capable of generating myeloid , T and B cells ) , bipotent progenitors p-MT , p-MB and p-TB , and unipotent progenitors p-M , p-T and p-B .", "annotated_text": "The multilineage progenitor ( MLP ) assay enabled us to discriminate among seven types of hematopoietic progenitors , which are multipotent progenitor p-MTB ( capable of generating <cell_type>myeloid , T and B cells</cell_type> ) , bipotent progenitors p-MT , p-MB and p-TB , and unipotent progenitors p-M , p-T and p-B ."}
{"id": "2245", "text": "Among these seven types , the p-TB type progenitor was found to be absent .", "annotated_text": "Among these seven types , the p-TB type progenitor was found to be absent ."}
{"id": "2246", "text": "These findings indicate that the process of lineage commitment proceeds through an ordered but not random process .", "annotated_text": "These findings indicate that the process of lineage commitment proceeds through an ordered but not random process ."}
{"id": "2247", "text": "By extending the area of investigation to include the erythroid lineage , more convincing evidence for the ordered process was obtained .", "annotated_text": "By extending the area of investigation to include the <cell_type>erythroid lineage</cell_type> , more convincing evidence for the ordered process was obtained ."}
{"id": "2248", "text": "Detailed and exact illustration of the process of hematopoiesis will provide an opportunity to revive hematopoiesis as one of the most fascinating targets of research in developmental biology", "annotated_text": "Detailed and exact illustration of the process of hematopoiesis will provide an opportunity to revive hematopoiesis as one of the most fascinating targets of research in developmental biology"}
{"id": "2249", "text": "Epstein-Barr Virus and its glycoprotein-350 upregulate IL-6 in human B-lymphocytes via CD21 , involving activation of NF-kappaB and different signaling pathways .", "annotated_text": "Epstein-Barr Virus and its <protein>glycoprotein-350</protein> upregulate <protein>IL-6</protein> in <cell_type>human B-lymphocytes</cell_type> via <protein>CD21</protein> , involving activation of <protein>NF-kappaB</protein> and different signaling pathways ."}
{"id": "2250", "text": "Epstein-Barr virus ( EBV ) is a ubiquitous and highly immunotropic gamma herpesvirus that infects more than 90 % of humans worldwide .", "annotated_text": "Epstein-Barr virus ( EBV ) is a ubiquitous and highly immunotropic gamma herpesvirus that infects more than 90 % of humans worldwide ."}
{"id": "2251", "text": "Its pathogenicity leads to a number of diseases including tumors that result from EBV 's ability to readily transform B-lymphocytes and , to a lesser extent , epithelial cells .", "annotated_text": "Its pathogenicity leads to a number of diseases including tumors that result from EBV 's ability to readily transform <cell_type>B-lymphocytes</cell_type> and , to a lesser extent , <cell_type>epithelial cells</cell_type> ."}
{"id": "2252", "text": "EBV utilizes CD21/CR2 as its receptor on B cells to initiate the infection process .", "annotated_text": "EBV utilizes <protein>CD21/CR2</protein> as its receptor on <cell_type>B cells</cell_type> to initiate the infection process ."}
{"id": "2253", "text": "EBV binds to CR2 through its major envelope glycoprotein-350 ( gp350 ) and is also a remarkable immunomodulating agent .", "annotated_text": "EBV binds to <protein>CR2</protein> through its <protein>major envelope glycoprotein-350</protein> ( <protein>gp350</protein> ) and is also a remarkable immunomodulating agent ."}
{"id": "2254", "text": "We had previously shown that EBV is capable of modulating the synthesis of a number of cytokines .", "annotated_text": "We had previously shown that EBV is capable of modulating the synthesis of a number of <protein>cytokines</protein> ."}
{"id": "2255", "text": "We now show that while both purified recombinant gp350 ( rgp350 ) and EBV upregulate IL-6 mRNA synthesis in B cells , EBV-induced IL-6 gene activation occurs for a significantly longer period of time ( i.e. 12 hours for EBV as compared to 6 hours for rgp350 ) .", "annotated_text": "We now show that while both purified <protein>recombinant gp350</protein> ( <protein>rgp350</protein> ) and EBV upregulate <rna>IL-6 mRNA</rna> synthesis in <cell_type>B cells</cell_type> , EBV-induced IL-6 gene activation occurs for a significantly longer period of time ( i.e. 12 hours for EBV as compared to 6 hours for <protein>rgp350</protein> ) ."}
{"id": "2256", "text": "Moreover , the half-life of EBV-induced IL-6 mRNA was also significantly longer ( 10 hours ) than that of mRNA induced by rgp350 ( about 6 hours ) .", "annotated_text": "Moreover , the half-life of EBV-induced <rna>IL-6 mRNA</rna> was also significantly longer ( 10 hours ) than that of mRNA induced by <protein>rgp350</protein> ( about 6 hours ) ."}
{"id": "2257", "text": "Both EBV and gp350 enhance the binding of the NF-kappaB transcription factor , as determined by band-shift and augment NF-kappaB -mediated activation of a CAT reporter plasmid .", "annotated_text": "Both EBV and <protein>gp350</protein> enhance the binding of the <protein>NF-kappaB transcription factor</protein> , as determined by band-shift and augment <protein>NF-kappaB</protein> -mediated activation of a <dna>CAT reporter plasmid</dna> ."}
{"id": "2258", "text": "Furthermore , we demonstrate that while the activation of IL-6 gene expression by gp350 is mediated primarily by the protein kinase C pathway , EBV can mediate its effects through multiple signaling pathways .", "annotated_text": "Furthermore , we demonstrate that while the activation of IL-6 gene expression by <protein>gp350</protein> is mediated primarily by the protein kinase C pathway , EBV can mediate its effects through multiple signaling pathways ."}
{"id": "2259", "text": "To our knowledge this is the first report showing that the binding of a herpesvirus envelope glycoprotein to CR2 on human B cells results in the activation of the NF-kappaB transcription factor leading to the upregulation of IL-6 gene expression in these lymphocytes .", "annotated_text": "To our knowledge this is the first report showing that the binding of a <protein>herpesvirus envelope glycoprotein</protein> to <protein>CR2</protein> on <cell_type>human B cells</cell_type> results in the activation of the <protein>NF-kappaB transcription factor</protein> leading to the upregulation of IL-6 gene expression in these <cell_type>lymphocytes</cell_type> ."}
{"id": "2260", "text": "Copyright 2001 Academic Press .", "annotated_text": "Copyright 2001 Academic Press ."}
{"id": "2261", "text": "Gene- and tissue-specificity of mutation in Big Blue rats treated with the hepatocarcinogen N-hydroxy-2-acetylaminofluorene .", "annotated_text": "Gene- and tissue-specificity of mutation in Big Blue rats treated with the hepatocarcinogen N-hydroxy-2-acetylaminofluorene ."}
{"id": "2262", "text": "In a previous study , we found that treating transgenic Big Blue rats with the hepatocarcinogen N-hydroxy-2-acetylaminofluorene ( N-OH-AAF ) produced the same major DNA adduct in the target liver and the nontarget spleen lymphocytes and bone marrow cells , induced lacI mutants in the liver , and induced much lower frequencies of l acI and hprt mutants in spleen lymphocytes .", "annotated_text": "In a previous study , we found that treating transgenic Big Blue rats with the hepatocarcinogen N-hydroxy-2-acetylaminofluorene ( N-OH-AAF ) produced the same major DNA adduct in the target liver and the <cell_type>nontarget spleen lymphocytes</cell_type> and <cell_type>bone marrow cells</cell_type> , induced <cell_type>lacI mutants</cell_type> in the liver , and induced much lower frequencies of l <cell_type>acI and hprt mutants</cell_type> in <cell_type>spleen lymphocytes</cell_type> ."}
{"id": "2263", "text": "In the present study , sequence analysis was conducted on lacI DNA and hprt cDNA from the mutants , to determine the mutational specificity of N-OH-AAF in the rat .", "annotated_text": "In the present study , sequence analysis was conducted on <dna>lacI DNA</dna> and <dna>hprt cDNA</dna> from the mutants , to determine the mutational specificity of N-OH-AAF in the rat ."}
{"id": "2264", "text": "All the mutation spectra from N-OH-AAF-treated rats differed significantly from corresponding mutation profiles from untreated animals ( P = 0.02 to P < 0.0001 ) .", "annotated_text": "All the mutation spectra from N-OH-AAF-treated rats differed significantly from corresponding mutation profiles from untreated animals ( P = 0.02 to P < 0.0001 ) ."}
{"id": "2265", "text": "Although there were similarities among the mutational patterns derived from N-OH-AAF-treated rats ( e.g. , G : C -- > T : A transversion was the most common mutation in all mutation sets ) , there were significant differences in the patterns of basepair substitution and frameshift mutation between the liver and spleen lymphocyte lacI mutants ( P = 0.02 ) and between the spleen lymphocyte lacI and hprt mutants ( P = 0.04 ) .", "annotated_text": "Although there were similarities among the mutational patterns derived from N-OH-AAF-treated rats ( e.g. , G : C -- > T : A transversion was the most common mutation in all mutation sets ) , there were significant differences in the patterns of basepair substitution and frameshift mutation between the liver and <cell_type>spleen lymphocyte lacI mutants</cell_type> ( P = 0.02 ) and between the <cell_type>spleen lymphocyte</cell_type> <cell_type>lacI and hprt mutants</cell_type> ( P = 0.04 ) ."}
{"id": "2266", "text": "Also , multiplex PCR analysis of genomic DNA from the hprt mutants indicated that 12 % of mutants from treated rats had major deletions in the hprt gene ; no corresponding incidence of large deletions was evident among lacI mutations .", "annotated_text": "Also , multiplex PCR analysis of <dna>genomic DNA</dna> from the <cell_type>hprt mutants</cell_type> indicated that 12 % of mutants from treated rats had major deletions in the <dna>hprt gene</dna> ; no corresponding incidence of large deletions was evident among lacI mutations ."}
{"id": "2267", "text": "All the mutation profiles reflect the general mutational specificity of the major DNA adduct formed by N-OH-AAF .", "annotated_text": "All the mutation profiles reflect the general mutational specificity of the major DNA adduct formed by N-OH-AAF ."}
{"id": "2268", "text": "The differences between N-OH-AAF mutation in the endogenous gene and transgene can be partially explained by the structures of the two genes .", "annotated_text": "The differences between N-OH-AAF mutation in the <dna>endogenous gene</dna> and <dna>transgene</dna> can be partially explained by the structures of the two genes ."}
{"id": "2269", "text": "The tissue-specificity of the mutation spectra may contribute to targeting tumor formation to the liver .", "annotated_text": "The tissue-specificity of the mutation spectra may contribute to targeting tumor formation to the liver ."}
{"id": "2270", "text": "Environ. Mol. Mutagen. 37 : 203-214 , 2001 .", "annotated_text": "Environ. Mol. Mutagen. 37 : 203-214 , 2001 ."}
{"id": "2271", "text": "Published 2001 Wiley-Liss , Inc .", "annotated_text": "Published 2001 Wiley-Liss , Inc ."}
{"id": "2272", "text": "Caspase -dependent cleavage of the hematopoietic specific adaptor protein Gads alters signalling from the T cell receptor .", "annotated_text": "<protein>Caspase</protein> -dependent cleavage of the <protein>hematopoietic specific adaptor protein Gads</protein> alters signalling from the <protein>T cell receptor</protein> ."}
{"id": "2273", "text": "Gads is a SH2 and SH3 domain -containing , hematopoietic-specific adaptor protein that functions in signalling from the T cell receptor .", "annotated_text": "<protein>Gads</protein> is a <protein>SH2 and SH3 domain</protein> -containing , <protein>hematopoietic-specific adaptor protein</protein> that functions in signalling from the <protein>T cell receptor</protein> ."}
{"id": "2274", "text": "Gads acts by linking SLP-76 , bound by the carboxy-terminal Gads SH3 domain , to tyrosine phosphorylated LAT which contains binding sites for the Gads SH2 domain .", "annotated_text": "<protein>Gads</protein> acts by linking <protein>SLP-76</protein> , bound by the <protein>carboxy-terminal Gads SH3 domain</protein> , to <protein>tyrosine phosphorylated LAT</protein> which contains binding sites for the <protein>Gads SH2 domain</protein> ."}
{"id": "2275", "text": "Gads is distinguished from Grb2 and the closely related Grap protein by the presence of a 120 amino acid unique region between the SH2 domain and the carboxy terminal SH3 domain .", "annotated_text": "<protein>Gads</protein> is distinguished from <protein>Grb2</protein> and the closely related <protein>Grap protein</protein> by the presence of a <protein>120 amino acid unique region</protein> between the <protein>SH2 domain</protein> and the <protein>carboxy terminal SH3 domain</protein> ."}
{"id": "2276", "text": "Here we demonstrate that the unique region of Gads contains a capase cleavage site .", "annotated_text": "Here we demonstrate that the unique region of <protein>Gads</protein> contains a <protein>capase cleavage site</protein> ."}
{"id": "2277", "text": "Induction of apoptosis in lymphocytes results in detectable Gads cleavage by 60 min .", "annotated_text": "Induction of apoptosis in <cell_type>lymphocytes</cell_type> results in detectable <protein>Gads</protein> cleavage by 60 min ."}
{"id": "2278", "text": "Gads cleavage is blocked in vivo by treating cells with a caspase 3 inhibitor .", "annotated_text": "<protein>Gads</protein> cleavage is blocked in vivo by treating cells with a caspase 3 inhibitor ."}
{"id": "2279", "text": "A putative caspase 3 cleavage site was identified within the unique region and mutation of this site prevented Gads cleavage in vitro , and in vivo .", "annotated_text": "A <protein>putative caspase 3 cleavage site</protein> was identified within the unique region and mutation of this site prevented <protein>Gads</protein> cleavage in vitro , and in vivo ."}
{"id": "2280", "text": "The Gads cleavage products retained the predicted binding specificity for SLP-76 and LAT .", "annotated_text": "The <protein>Gads</protein> cleavage products retained the predicted binding specificity for <protein>SLP-76</protein> and <protein>LAT</protein> ."}
{"id": "2281", "text": "Expression of the Gads cleavage products in Jurkat T cells inhibited NFAT activation following TCR cross linking .", "annotated_text": "Expression of the <protein>Gads</protein> cleavage products in <cell_line>Jurkat T cells</cell_line> inhibited NFAT activation following TCR cross linking ."}
{"id": "2282", "text": "These findings indicate that cleavage of Gads in vivo could function to alter signalling downstream of the T cell receptor by disrupting cross talk between SLP-76 and LAT .", "annotated_text": "These findings indicate that cleavage of <protein>Gads</protein> in vivo could function to alter signalling downstream of the <protein>T cell receptor</protein> by disrupting cross talk between <protein>SLP-76</protein> and <protein>LAT</protein> ."}
{"id": "2283", "text": "Targeting of p300 to the interleukin-2 promoter via CREB-Rel cross-talk during mitogen and oncogenic molecular signaling in activated T-cells .", "annotated_text": "Targeting of <protein>p300</protein> to the <dna>interleukin-2 promoter</dna> via CREB-Rel cross-talk during <protein>mitogen</protein> and oncogenic molecular signaling in <cell_type>activated T-cells</cell_type> ."}
{"id": "2284", "text": "In this report , we explore the mechanisms of targeting of p300 to the interleukin-2 ( IL-2 ) promoter in response to mitogenic and oncogenic molecular signals .", "annotated_text": "In this report , we explore the mechanisms of targeting of <protein>p300</protein> to the <dna>interleukin-2 ( IL-2 ) promoter</dna> in response to mitogenic and oncogenic molecular signals ."}
{"id": "2285", "text": "Recruitment of p300 by cAMP-responsive element-binding protein-Rel cross-talk at the composite CD28 response element ( CD28RE ) - TRE element of the IL-2 promoter is essential for promoter inducibility during T-cell activation , and CD28RE-TRE is the exclusive target of the human T-cell lymphotropic virus type I oncoprotein Tax .", "annotated_text": "Recruitment of <protein>p300</protein> by <protein>cAMP-responsive element-binding protein-Rel</protein> cross-talk at the <protein>composite CD28 response element</protein> ( <protein>CD28RE</protein> ) - <dna>TRE element</dna> of the <dna>IL-2 promoter</dna> is essential for promoter inducibility during T-cell activation , and <dna>CD28RE-TRE</dna> is the exclusive target of the <cell_type>human T-cell</cell_type> lymphotropic virus type I <protein>oncoprotein Tax</protein> ."}
{"id": "2286", "text": "The intrinsic histone acetyltransferase activity of p300 is dispensable for activation of the IL-2 promoter , and the N-terminal 743 residues contain the minimal structural requirements for synergistic transactivation of the CD28RE-TRE , the IL-2 promoter , and endogenous IL-2 gene expression .", "annotated_text": "The intrinsic histone acetyltransferase activity of <protein>p300</protein> is dispensable for activation of the <dna>IL-2 promoter</dna> , and the <protein>N-terminal 743 residues</protein> contain the minimal structural requirements for synergistic transactivation of the <dna>CD28RE-TRE</dna> , the <dna>IL-2 promoter</dna> , and endogenous <dna>IL-2 gene</dna> expression ."}
{"id": "2287", "text": "Mutational analysis of p300 reveals differential structural requirements for the N-terminal p300 module by individual cis-elements within the IL-2 promoter .", "annotated_text": "Mutational analysis of <protein>p300</protein> reveals differential structural requirements for the N-terminal p300 module by individual <dna>cis-elements</dna> within the <dna>IL-2 promoter</dna> ."}
{"id": "2288", "text": "These findings provide evidence that p300 assembles at the IL-2 promoter to form an enhanceosome-like signal transduction target that is centrally integrated at the CD28RE-TRE element of the IL-2 promoter through specific protein module-targeted associations in activated T-cells .", "annotated_text": "These findings provide evidence that <protein>p300</protein> assembles at the <dna>IL-2 promoter</dna> to form an enhanceosome-like signal transduction target that is centrally integrated at the <dna>CD28RE-TRE element</dna> of the <dna>IL-2 promoter</dna> through specific protein module-targeted associations in <cell_type>activated T-cells</cell_type> ."}
{"id": "2289", "text": "Regulation of cytokine production in T-cell responses to inhalant allergen : GATA-3 expression distinguishes between Th1- and Th2-polarized immunity .", "annotated_text": "Regulation of cytokine production in <cell_type>T-cell</cell_type> responses to inhalant allergen : <protein>GATA-3</protein> expression distinguishes between Th1- and Th2-polarized immunity ."}
{"id": "2290", "text": "BACKGROUND : The precise nature of allergen-specific cytokine responses in atopics versus non-atopics , in particular the 'Th1 polarity ' of responses in non-atopics , remains controversial .", "annotated_text": "BACKGROUND : The precise nature of allergen-specific cytokine responses in atopics versus non-atopics , in particular the 'Th1 polarity ' of responses in non-atopics , remains controversial ."}
{"id": "2291", "text": "This is due in part to the relative insensitivity of cytokine detection systems , and associated variations in kinetics of cytokine production and catabolism in in vitro culture systems .", "annotated_text": "This is due in part to the relative insensitivity of cytokine detection systems , and associated variations in kinetics of cytokine production and catabolism in in vitro culture systems ."}
{"id": "2292", "text": "As an alternative to cytokine measurement , this study focuses on expression of the transcription factor GATA-3 for analysis of allergen-specific Th cell responses .", "annotated_text": "As an alternative to cytokine measurement , this study focuses on expression of the <protein>transcription factor GATA-3</protein> for analysis of allergen-specific Th cell responses ."}
{"id": "2293", "text": "METHODS : Cord blood mononuclear cells were Th1- or Th2-polarized by culture in IL-12- or IL-4-employing established methods ; PBMC from house dust mite ( HDM ) -sensitive atopics and controls were stimulated overnight with HDM ; cytokine production was measured by ELISA and GATA-3 mRNA expression by PCR .", "annotated_text": "METHODS : <cell_type>Cord blood mononuclear cells</cell_type> were Th1- or Th2-polarized by culture in IL-12- or IL-4-employing established methods ; <cell_type>PBMC</cell_type> from house dust mite ( HDM ) -sensitive atopics and controls were stimulated overnight with HDM ; cytokine production was measured by ELISA and <rna>GATA-3 mRNA</rna> expression by PCR ."}
{"id": "2294", "text": "RESULTS : Cytokine -driven Th2 polarization of naive T cells is associated with marked upregulation of GATA-3 expression , whereas a reciprocal expression pattern accompanies differentiation towards the Th1 cytokine phenotype .", "annotated_text": "RESULTS : <protein>Cytokine</protein> -driven Th2 polarization of <cell_type>naive T cells</cell_type> is associated with marked upregulation of <protein>GATA-3</protein> expression , whereas a reciprocal expression pattern accompanies differentiation towards the Th1 cytokine phenotype ."}
{"id": "2295", "text": "In T cells from HDM skin prick test-positive ( HDM-SPT+/HDM-IgE+ ) volunteers , overnight stimulation results in marked upregulation of GATA-3 expression , compared to an equally marked downregulation of expression in T cells from SPT-/IgE- subjects .", "annotated_text": "In <cell_type>T cells</cell_type> from HDM skin prick test-positive ( HDM-SPT+/HDM-IgE+ ) volunteers , overnight stimulation results in marked upregulation of <protein>GATA-3</protein> expression , compared to an equally marked downregulation of expression in <cell_type>T cells</cell_type> from SPT-/IgE- subjects ."}
{"id": "2296", "text": "In subjects who are HDM-SPT+ but IgE- , GATA-3 expression levels remained relatively stable during culture with HDM .", "annotated_text": "In subjects who are HDM-SPT+ but IgE- , <protein>GATA-3</protein> expression levels remained relatively stable during culture with HDM ."}
{"id": "2297", "text": "CONCLUSIONS : Upregulation of GATA-3 expression in PBMC is a hallmark of the early phase of Th2 recall responses to specific allergen in atopics .", "annotated_text": "CONCLUSIONS : Upregulation of <protein>GATA-3</protein> expression in <cell_type>PBMC</cell_type> is a hallmark of the early phase of Th2 recall responses to specific allergen in atopics ."}
{"id": "2298", "text": "The reciprocal expression pattern observed in HDM-specific recall responses of non-atopics provides independent confirmation of the presence of underlying Th1-like immunity in these subjects .", "annotated_text": "The reciprocal expression pattern observed in HDM-specific recall responses of non-atopics provides independent confirmation of the presence of underlying Th1-like immunity in these subjects ."}
{"id": "2299", "text": "The parallel findings in neonatal T cells suggest that the same approach may be utilized for monitoring the progress of allergen-specific Th1/Th2 memory development during early childhood , and hence in assessment of risk for future allergic disease .", "annotated_text": "The parallel findings in <cell_type>neonatal T cells</cell_type> suggest that the same approach may be utilized for monitoring the progress of allergen-specific Th1/Th2 memory development during early childhood , and hence in assessment of risk for future allergic disease ."}
{"id": "2300", "text": "Copyright 2001 S. Karger AG , Basel", "annotated_text": "Copyright 2001 S. Karger AG , Basel"}
{"id": "2301", "text": "The heat shock response reduces myelin oligodendrocyte glycoprotein -induced experimental autoimmune encephalomyelitis in mice .", "annotated_text": "The heat shock response reduces <protein>myelin oligodendrocyte glycoprotein</protein> -induced experimental autoimmune encephalomyelitis in mice ."}
{"id": "2302", "text": "The stress response ( SR ) can block inflammatory gene expression by preventing activation of transcription factor nuclear factor-kappa B ( NF-kappaB ) .", "annotated_text": "The stress response ( SR ) can block inflammatory gene expression by preventing activation of <protein>transcription factor</protein> <protein>nuclear factor-kappa B</protein> ( <protein>NF-kappaB</protein> ) ."}
{"id": "2303", "text": "As inflammatory gene expression contributes to the pathogenesis of demyelinating diseases , we tested the effects of the SR on the progression of the demyelinating disease experimental autoimmune encephalomyelitis ( EAE ) .", "annotated_text": "As inflammatory gene expression contributes to the pathogenesis of demyelinating diseases , we tested the effects of the SR on the progression of the demyelinating disease experimental autoimmune encephalomyelitis ( EAE ) ."}
{"id": "2304", "text": "EAE was actively induced in C57BL/6 mice using an encephalitogenic myelin oligodendrocyte glycoprotein ( MOG ( 35-55 ) ) peptide .", "annotated_text": "EAE was actively induced in C57BL/6 mice using an encephalitogenic <protein>myelin oligodendrocyte glycoprotein</protein> ( <protein>MOG ( 35-55 )</protein> ) peptide ."}
{"id": "2305", "text": "Whole body hyperthermia was used to induce a heat shock response ( HSR ) in immunized mice 2 days after the booster MOG ( 35-55 ) peptide injection .", "annotated_text": "Whole body hyperthermia was used to induce a heat shock response ( HSR ) in immunized mice 2 days after the booster MOG ( 35-55 ) peptide injection ."}
{"id": "2306", "text": "The HSR reduced the incidence of EAE by 70 % , delayed disease onset by 6 days , and attenuated disease severity .", "annotated_text": "The HSR reduced the incidence of EAE by 70 % , delayed disease onset by 6 days , and attenuated disease severity ."}
{"id": "2307", "text": "The HSR attenuated leukocyte infiltration into CNS assessed by quantitation of perivascular infiltrates , and by reduced staining for CD4 and CD25 immunopositive T-cells .", "annotated_text": "The HSR attenuated <cell_type>leukocyte</cell_type> infiltration into CNS assessed by quantitation of perivascular infiltrates , and by reduced staining for <protein>CD4</protein> and <protein>CD25</protein> immunopositive <cell_type>T-cells</cell_type> ."}
{"id": "2308", "text": "T-cell activation , assessed by the production of interferon gamma ( IFNgamma ) in response to MOG ( 35-55 ) , was also decreased by the HSR .", "annotated_text": "T-cell activation , assessed by the production of <protein>interferon gamma</protein> ( <protein>IFNgamma</protein> ) in response to <protein>MOG ( 35-55 )</protein> , was also decreased by the HSR ."}
{"id": "2309", "text": "The HSR reduced inflammatory gene expression in the brain that normally occurs during EAE , including the early increase in RANTES ( regulated on activation of normal T-cell expressed and secreted ) expression , and the later expression of the inducible form of nitric oxide synthase .", "annotated_text": "The HSR reduced inflammatory gene expression in the brain that normally occurs during EAE , including the early increase in <protein>RANTES</protein> ( <protein>regulated on activation of normal T-cell expressed and secreted</protein> ) expression , and the later expression of the inducible form of <protein>nitric oxide synthase</protein> ."}
{"id": "2310", "text": "The early activation of transcription factor NF-kappaB was also blocked by the HSR .", "annotated_text": "The early activation of <protein>transcription factor</protein> <protein>NF-kappaB</protein> was also blocked by the HSR ."}
{"id": "2311", "text": "The finding that the SR reduces inflammation in the brain and the clinical severity of EAE opens a novel therapeutic approach for prevention of autoimmune diseases .", "annotated_text": "The finding that the SR reduces inflammation in the brain and the clinical severity of EAE opens a novel therapeutic approach for prevention of autoimmune diseases ."}
{"id": "2312", "text": "In vivo detection of intracellular signaling pathways in developing thymocytes .", "annotated_text": "In vivo detection of intracellular signaling pathways in developing <cell_type>thymocytes</cell_type> ."}
{"id": "2313", "text": "Information regarding the intracellular signaling processes that occur during the development of T cells has largely been obtained with the use of transgenic mouse models , which although providing invaluable information are time consuming and costly .", "annotated_text": "Information regarding the intracellular signaling processes that occur during the development of <cell_type>T cells</cell_type> has largely been obtained with the use of transgenic mouse models , which although providing invaluable information are time consuming and costly ."}
{"id": "2314", "text": "To this end , we have developed a novel system that facilitates the in vivo analysis of signal transduction pathways during T-lymphocyte development .", "annotated_text": "To this end , we have developed a novel system that facilitates the in vivo analysis of signal transduction pathways during <cell_type>T-lymphocyte</cell_type> development ."}
{"id": "2315", "text": "This approach uses reporter-plasmids for the detection of intracellular signals mediated by the mitogen-activated protein kinase or cyclic AMP-dependent protein kinase .", "annotated_text": "This approach uses <dna>reporter-plasmids</dna> for the detection of intracellular signals mediated by the <protein>mitogen-activated protein kinase</protein> or <protein>cyclic AMP-dependent protein kinase</protein> ."}
{"id": "2316", "text": "Reporter-plasmids are transfected into thymocytes in fetal thymic organ culture by accelerated DNA/particle bombardment ( gene gun ) , and the activation of a signaling pathway is determined in the form of a standard luciferase assay .", "annotated_text": "<dna>Reporter-plasmids</dna> are transfected into <cell_type>thymocytes</cell_type> in fetal thymic organ culture by accelerated DNA/particle bombardment ( gene gun ) , and the activation of a signaling pathway is determined in the form of a standard luciferase assay ."}
{"id": "2317", "text": "Importantly , this powerful technique preserves the structural integrity of the thymus , and will provide an invaluable tool to study how thymocytes respond to normal environmental stimuli encountered during differentiation within the thymic milieu .", "annotated_text": "Importantly , this powerful technique preserves the structural integrity of the thymus , and will provide an invaluable tool to study how <cell_type>thymocytes</cell_type> respond to normal environmental stimuli encountered during differentiation within the thymic milieu ."}
{"id": "2318", "text": "Thus , this method allows for the monitoring of signals that occur in a biological time frame , such as during differentiation , and within the natural environment of differentiating cells .", "annotated_text": "Thus , this method allows for the monitoring of signals that occur in a biological time frame , such as during differentiation , and within the natural environment of <cell_type>differentiating cells</cell_type> ."}
{"id": "2319", "text": "Core-binding factor beta ( CBFbeta ) , but not CBFbeta-smooth muscle myosin heavy chain , rescues definitive hematopoiesis in CBFbeta -deficient embryonic stem cells .", "annotated_text": "<protein>Core-binding factor beta</protein> ( <protein>CBFbeta</protein> ) , but not <protein>CBFbeta-smooth muscle myosin heavy chain</protein> , rescues definitive hematopoiesis in <protein>CBFbeta</protein> -deficient <cell_type>embryonic stem cells</cell_type> ."}
{"id": "2320", "text": "Core-binding factor beta ( CBFbeta ) is the non-DNA-binding subunit of the heterodimeric CBFs .", "annotated_text": "<protein>Core-binding factor beta</protein> ( <protein>CBFbeta</protein> ) is the <protein>non-DNA-binding subunit</protein> of the <protein>heterodimeric CBFs</protein> ."}
{"id": "2321", "text": "Genes encoding CBFbeta ( CBFB ) , and one of the DNA-binding CBFalpha subunits , Runx1 ( also known as CBFalpha2 , AML1 , and PEBP2alphaB ) , are required for normal hematopoiesis and are also frequent targets of chromosomal translocations in acute leukemias in humans .", "annotated_text": "<dna>Genes encoding CBFbeta</dna> ( <dna>CBFB</dna> ) , and one of the <protein>DNA-binding CBFalpha subunits , Runx1</protein> ( also known as <protein>CBFalpha2</protein> , <protein>AML1</protein> , and <protein>PEBP2alphaB</protein> ) , are required for normal hematopoiesis and are also frequent targets of chromosomal translocations in acute leukemias in humans ."}
{"id": "2322", "text": "Homozygous disruption of either the Runx1 or Cbfb gene in mice results in embryonic lethality at midgestation due to hemorrhaging in the central nervous system , and severely impairs fetal liver hematopoiesis .", "annotated_text": "Homozygous disruption of either the <dna>Runx1 or Cbfb gene</dna> in mice results in embryonic lethality at midgestation due to hemorrhaging in the central nervous system , and severely impairs fetal liver hematopoiesis ."}
{"id": "2323", "text": "Results of this study show that Cbfb-deficient mouse embryonic stem ( ES ) cells can differentiate into primitive erythroid colonies in vitro , but are impaired in their ability to produce definitive erythroid and myeloid colonies , mimicking the in vivo defect .", "annotated_text": "Results of this study show that Cbfb-deficient mouse <cell_type>embryonic stem ( ES ) cells</cell_type> can differentiate into <cell_type>primitive erythroid colonies</cell_type> in vitro , but are impaired in their ability to produce definitive <cell_type>erythroid and myeloid colonies</cell_type> , mimicking the in vivo defect ."}
{"id": "2324", "text": "Definitive hematopoiesis is restored by ectopic expression of full-length Cbfb transgenes , as well as by a transgene encoding only the heterodimerization domain of CBFbeta .", "annotated_text": "Definitive hematopoiesis is restored by ectopic expression of <dna>full-length Cbfb transgenes</dna> , as well as by a transgene encoding only the <protein>heterodimerization domain</protein> of <protein>CBFbeta</protein> ."}
{"id": "2325", "text": "In contrast , the CBFbeta - smooth muscle myosin heavy chain ( SMMHC ) fusion protein generated by the inv ( 16 ) associated with acute myeloid leukemias ( M4Eo ) can not rescue definitive hematopoiesis by Cbfb-deficient ES cells .", "annotated_text": "In contrast , the <protein>CBFbeta</protein> - <protein>smooth muscle myosin heavy chain ( SMMHC ) fusion protein</protein> generated by the <protein>inv ( 16 )</protein> associated with <cell_line>acute myeloid leukemias</cell_line> ( <cell_line>M4Eo</cell_line> ) can not rescue definitive hematopoiesis by <cell_type>Cbfb-deficient ES cells</cell_type> ."}
{"id": "2326", "text": "Sequences responsible for the inability of CBFbeta -SMMHC to rescue definitive hematopoiesis reside in the SMMHC portion of the fusion protein .", "annotated_text": "Sequences responsible for the inability of <protein>CBFbeta</protein> -SMMHC to rescue definitive hematopoiesis reside in the <protein>SMMHC portion</protein> of the <protein>fusion protein</protein> ."}
{"id": "2327", "text": "Results also show that the CBFbeta-SMMHC fusion protein transdominantly inhibits definitive hematopoiesis , but not to the same extent as homozygous loss of Runx1 or Cbfb .", "annotated_text": "Results also show that the <protein>CBFbeta-SMMHC fusion protein</protein> transdominantly inhibits definitive hematopoiesis , but not to the same extent as homozygous loss of <protein>Runx1</protein> or <protein>Cbfb</protein> ."}
{"id": "2328", "text": "CBFbeta-SMMHC preferentially inhibits the differentiation of myeloid lineage cells , while increasing the number of blastlike cells in culture .", "annotated_text": "<protein>CBFbeta-SMMHC</protein> preferentially inhibits the differentiation of <cell_type>myeloid lineage cells</cell_type> , while increasing the number of <cell_type>blastlike cells</cell_type> in culture ."}
{"id": "2329", "text": "The latency pattern of Epstein-Barr virus infection and viral IL-10 expression in cutaneous natural killer/T-cell lymphomas .", "annotated_text": "The latency pattern of Epstein-Barr virus infection and viral <protein>IL-10</protein> expression in <cell_type>cutaneous natural killer/T-cell lymphomas</cell_type> ."}
{"id": "2330", "text": "The nasal type , extranodal natural killer or T ( NK/T ) -cell lymphoma is usually associated with latent Epstein-Barr virus ( EBV ) infection .", "annotated_text": "The <cell_type>nasal type , extranodal natural killer or T ( NK/T ) -cell lymphoma</cell_type> is usually associated with latent Epstein-Barr virus ( EBV ) infection ."}
{"id": "2331", "text": "In order to elucidate the EBV gene expression patterns in vivo , we examined eight patients with cutaneous EBV-related NK/T-cell lymphomas , including six patients with a NK-cell phenotype and two patients with a T-cell phenotype .", "annotated_text": "In order to elucidate the EBV gene expression patterns in vivo , we examined eight patients with cutaneous EBV-related NK/T-cell lymphomas , including six patients with a NK-cell phenotype and two patients with a T-cell phenotype ."}
{"id": "2332", "text": "The implication of EBV in the skin lesions was determined by the presence of EBV-DNA , EBV-encoded nuclear RNA ( EBER ) and a clonality of EBV-DNA fragments containing the terminal repeats .", "annotated_text": "The implication of EBV in the skin lesions was determined by the presence of <dna>EBV-DNA</dna> , <rna>EBV-encoded nuclear RNA</rna> ( <rna>EBER</rna> ) and a clonality of <dna>EBV-DNA fragments</dna> containing the <dna>terminal repeats</dna> ."}
{"id": "2333", "text": "Transcripts of EBV-encoded genes were screened by reverse transcription- polymerase chain reaction ( RT-PCR ) , and confirmed by Southern blot hybridization .", "annotated_text": "Transcripts of <dna>EBV-encoded genes</dna> were screened by reverse transcription- polymerase chain reaction ( RT-PCR ) , and confirmed by Southern blot hybridization ."}
{"id": "2334", "text": "The expression of EBV-related antigens was examined by immunostaining using paraffin-embedded tissue sections and cell pellets of EBV-positive cell lines .", "annotated_text": "The expression of <protein>EBV-related antigens</protein> was examined by immunostaining using paraffin-embedded tissue sections and cell pellets of <cell_line>EBV-positive cell lines</cell_line> ."}
{"id": "2335", "text": "Our study demonstrated that all samples from the patients contained EBV nuclear antigen ( EBNA ) -1 mRNA which was transcribed using the Q promoter , whereas both the Q promoter and another upstream promoter ( Cp/Wp ) were used in EBV-positive cell lines , B95.8 , Raji and Jiyoye .", "annotated_text": "Our study demonstrated that all samples from the patients contained <rna>EBV nuclear antigen ( EBNA ) -1 mRNA</rna> which was transcribed using the <dna>Q promoter</dna> , whereas both the <dna>Q promoter</dna> and another <dna>upstream promoter</dna> ( <dna>Cp/Wp</dna> ) were used in <cell_line>EBV-positive cell lines</cell_line> , <cell_line>B95.8</cell_line> , <cell_line>Raji</cell_line> and <cell_line>Jiyoye</cell_line> ."}
{"id": "2336", "text": "Latent membrane protein-1 ( LMP-1 ) mRNA was detected in seven of eight patients and all cell lines , whereas EBNA-2 transcripts were found only in the cell lines .", "annotated_text": "<rna>Latent membrane protein-1 ( LMP-1 ) mRNA</rna> was detected in seven of eight patients and all <cell_line>cell lines</cell_line> , whereas <rna>EBNA-2 transcripts</rna> were found only in the <cell_line>cell lines</cell_line> ."}
{"id": "2337", "text": "Immunostaining showed no LMP-1 , EBNA-2 or ZEBRA antigens in the paraffin-embedded tissue sections , although they were positive in the cell line cells .", "annotated_text": "Immunostaining showed no <protein>LMP-1 , EBNA-2 or ZEBRA antigens</protein> in the paraffin-embedded tissue sections , although they were positive in the <cell_line>cell line cells</cell_line> ."}
{"id": "2338", "text": "Latent BHRF1 transcripts encoding bcl-2 homologue and BCRF1 transcripts encoding viral interleukin ( vIL ) -10 were detected in one and two of eight patients , respectively .", "annotated_text": "<rna>Latent BHRF1 transcripts</rna> encoding <rna>bcl-2 homologue</rna> and <rna>BCRF1 transcripts</rna> encoding <protein>viral interleukin ( vIL ) -10</protein> were detected in one and two of eight patients , respectively ."}
{"id": "2339", "text": "A patient with NK-cell lymphoma expressing both transcripts died of rapid progression of the illness .", "annotated_text": "A patient with NK-cell lymphoma expressing both transcripts died of rapid progression of the illness ."}
{"id": "2340", "text": "Our results indicate that the restricted expression of the latency-associated EBV genes and the production of vIL-10 and bcl-2 homologue may favour tumour growth , evading the host immune surveillance .", "annotated_text": "Our results indicate that the restricted expression of the <dna>latency-associated EBV genes</dna> and the production of <rna>vIL-10 and bcl-2 homologue</rna> may favour tumour growth , evading the host immune surveillance ."}
{"id": "2341", "text": "Copyright 2001 Cancer Research Campaign .", "annotated_text": "Copyright 2001 Cancer Research Campaign ."}
{"id": "2342", "text": "Oxidized alkyl phospholipids are specific , high affinity peroxisome proliferator-activated receptor gamma ligands and agonists .", "annotated_text": "Oxidized alkyl phospholipids are specific , high affinity peroxisome proliferator-activated receptor gamma ligands and agonists ."}
{"id": "2343", "text": "Synthetic high affinity peroxisome proliferator-activated receptor ( PPAR ) agonists are known , but biologic ligands are of low affinity .", "annotated_text": "Synthetic high affinity peroxisome proliferator-activated receptor ( PPAR ) agonists are known , but biologic ligands are of low affinity ."}
{"id": "2344", "text": "Oxidized low density lipoprotein ( oxLDL ) is inflammatory and signals through PPARs .", "annotated_text": "<protein>Oxidized low density lipoprotein</protein> ( <protein>oxLDL</protein> ) is inflammatory and signals through <protein>PPARs</protein> ."}
{"id": "2345", "text": "We showed , by phospholipase A ( 1 ) digestion , that PPARgamma agonists in oxLDL arise from the small pool of alkyl phosphatidylcholines in LDL .", "annotated_text": "We showed , by phospholipase A ( 1 ) digestion , that PPARgamma agonists in <protein>oxLDL</protein> arise from the small pool of alkyl phosphatidylcholines in <protein>LDL</protein> ."}
{"id": "2346", "text": "We identified an abundant oxidatively fragmented alkyl phospholipid in oxLDL , hexadecyl azelaoyl phosphatidylcholine ( azPC ) , as a high affinity ligand and agonist for PPARgamma .", "annotated_text": "We identified an abundant oxidatively fragmented alkyl phospholipid in <protein>oxLDL</protein> , hexadecyl azelaoyl phosphatidylcholine ( azPC ) , as a high affinity ligand and agonist for <protein>PPARgamma</protein> ."}
{"id": "2347", "text": "[ ( 3 ) H ] azPC bound recombinant PPARgamma with an affinity ( K ( d ) ( ( app ) ) approximately 40 nm ) that was equivalent to rosiglitazone ( BRL49653 ) , and competition with rosiglitazone showed that binding occurred in the ligand-binding pocket .", "annotated_text": "[ ( 3 ) H ] azPC bound <protein>recombinant PPARgamma</protein> with an affinity ( K ( d ) ( ( app ) ) approximately 40 nm ) that was equivalent to rosiglitazone ( BRL49653 ) , and competition with rosiglitazone showed that binding occurred in the <protein>ligand-binding pocket</protein> ."}
{"id": "2348", "text": "azPC induced PPRE reporter gene expression , as did rosiglitazone , with a half-maximal effect at 100 nm .", "annotated_text": "azPC induced PPRE reporter gene expression , as did rosiglitazone , with a half-maximal effect at 100 nm ."}
{"id": "2349", "text": "Overexpression of PPARalpha or PPARgamma revealed that azPC was a specific PPARgamma agonist .", "annotated_text": "Overexpression of <protein>PPARalpha</protein> or <protein>PPARgamma</protein> revealed that azPC was a specific PPARgamma agonist ."}
{"id": "2350", "text": "The scavenger receptor CD36 is encoded by a PPRE-responsive gene , and azPC enhanced expression of CD36 in primary human monocytes .", "annotated_text": "The <protein>scavenger receptor CD36</protein> is encoded by a <dna>PPRE-responsive gene</dna> , and azPC enhanced expression of <protein>CD36</protein> in <cell_type>primary human monocytes</cell_type> ."}
{"id": "2351", "text": "We found that anti-CD36 inhibited azPC uptake , and it inhibited PPRE reporter induction .", "annotated_text": "We found that <protein>anti-CD36</protein> inhibited azPC uptake , and it inhibited PPRE reporter induction ."}
{"id": "2352", "text": "Results with a small molecule phospholipid flippase mimetic suggest azPC acts intracellularly and that cellular azPC accumulation was efficient .", "annotated_text": "Results with a small molecule <protein>phospholipid flippase mimetic</protein> suggest azPC acts intracellularly and that cellular azPC accumulation was efficient ."}
{"id": "2353", "text": "Thus , certain alkyl phospholipid oxidation products in oxLDL are specific , high affinity extracellular ligands and agonists for PPARgamma that induce PPAR-responsive genes", "annotated_text": "Thus , certain alkyl phospholipid oxidation products in <protein>oxLDL</protein> are specific , high affinity extracellular ligands and agonists for <protein>PPARgamma</protein> that induce <dna>PPAR-responsive genes</dna>"}
{"id": "2354", "text": "Regulation of the human MAT2B gene encoding the regulatory beta subunit of methionine adenosyltransferase , MAT II .", "annotated_text": "Regulation of the <dna>human MAT2B gene</dna> encoding the <protein>regulatory beta subunit</protein> of <protein>methionine adenosyltransferase</protein> , <protein>MAT II</protein> ."}
{"id": "2355", "text": "Methionine adenosyltransferase ( MAT ) catalyzes the biosynthesis of S-adenosylmethionine ( AdoMet ) , a key molecule in transmethylation reactions and polyamine biosynthesis .", "annotated_text": "<protein>Methionine adenosyltransferase</protein> ( <protein>MAT</protein> ) catalyzes the biosynthesis of <protein>S-adenosylmethionine</protein> ( <protein>AdoMet</protein> ) , a key molecule in transmethylation reactions and polyamine biosynthesis ."}
{"id": "2356", "text": "The MAT II isozyme consists of a catalytic alpha2 and a regulatory beta subunit .", "annotated_text": "The <protein>MAT II isozyme</protein> consists of a <protein>catalytic alpha2 and a regulatory beta subunit</protein> ."}
{"id": "2357", "text": "Down-regulation of the MAT II beta subunit expression causes a 6-10-fold increase in intracellular AdoMet levels .", "annotated_text": "Down-regulation of the <protein>MAT II beta subunit</protein> expression causes a 6-10-fold increase in intracellular <protein>AdoMet</protein> levels ."}
{"id": "2358", "text": "To understand the mechanism by which the beta subunit expression is regulated , we cloned the MAT2B gene , determined its organization , characterized its 5'-flanking sequences , and elucidated the in vitro and in vivo regulation of its promoter .", "annotated_text": "To understand the mechanism by which the <protein>beta subunit</protein> expression is regulated , we cloned the <dna>MAT2B gene</dna> , determined its organization , characterized its <dna>5'-flanking sequences</dna> , and elucidated the in vitro and in vivo regulation of its <dna>promoter</dna> ."}
{"id": "2359", "text": "Transcription of the MAT2B gene initiates at position -203 relative to the translation start site .", "annotated_text": "Transcription of the <dna>MAT2B gene</dna> initiates at position -203 relative to the <dna>translation start site</dna> ."}
{"id": "2360", "text": "Promoter deletion analysis defined a minimal promoter between positions +52 and +93 base pairs , a GC-rich region .", "annotated_text": "<dna>Promoter deletion analysis</dna> defined a <dna>minimal promoter</dna> between <dna>positions +52 and +93</dna> base pairs , a <dna>GC-rich region</dna> ."}
{"id": "2361", "text": "Inclusion of the sequences between -4 and +52 enhanced promoter activity ; this was primarily because of an Sp1 recognition site at +9/+15 .", "annotated_text": "Inclusion of the sequences between -4 and +52 enhanced promoter activity ; this was primarily because of an <dna>Sp1 recognition site</dna> at +9/+15 ."}
{"id": "2362", "text": "The inclusion of sequences up to position -115 provided full activity ; this was attributed to a TATA at -32 .", "annotated_text": "The inclusion of sequences up to position -115 provided full activity ; this was attributed to a <dna>TATA</dna> at -32 ."}
{"id": "2363", "text": "The Sp1 site at position +9 was key for the formation of protein.DNA complexes .", "annotated_text": "The <dna>Sp1 site</dna> at position +9 was key for the formation of protein.DNA complexes ."}
{"id": "2364", "text": "Mutation of both the Sp1 site at +9 and the TATA at -32 reduced promoter activity to its minimal level .", "annotated_text": "Mutation of both the <dna>Sp1 site</dna> at +9 and the <dna>TATA</dna> at -32 reduced promoter activity to its minimal level ."}
{"id": "2365", "text": "Supershift assays showed no effect of the anti-Sp1 antibody on complex formation , whereas the anti-Sp3 antibody had a strong effect on protein.DNA complex formation , suggesting that Sp3 is one of the main factors binding to this Sp1 site .", "annotated_text": "Supershift assays showed no effect of the <protein>anti-Sp1 antibody</protein> on complex formation , whereas the <protein>anti-Sp3 antibody</protein> had a strong effect on protein.DNA complex formation , suggesting that <protein>Sp3</protein> is one of the main factors binding to this <dna>Sp1 site</dna> ."}
{"id": "2366", "text": "Chromatin immunoprecipitation assays supported the involvement of both Sp1 and Sp3 in complexes formed on the MAT2B promoter .", "annotated_text": "Chromatin immunoprecipitation assays supported the involvement of both <protein>Sp1</protein> and <protein>Sp3</protein> in complexes formed on the <dna>MAT2B promoter</dna> ."}
{"id": "2367", "text": "The data show that the 5'-untranslated sequences play an important role in regulating the MAT2B gene and identifies the Sp1 site at +9 as a potential target for modulating MAT2B expression , a process that can have a major effect on intracellular AdoMet levels .", "annotated_text": "The data show that the <dna>5'-untranslated sequences</dna> play an important role in regulating the <dna>MAT2B gene</dna> and identifies the <dna>Sp1 site</dna> at +9 as a potential target for modulating MAT2B expression , a process that can have a major effect on intracellular <protein>AdoMet</protein> levels ."}
{"id": "2368", "text": "Molecular pathogenesis of influenza A virus infection and virus-induced regulation of cytokine gene expression .", "annotated_text": "Molecular pathogenesis of influenza A virus infection and virus-induced regulation of <dna>cytokine gene</dna> expression ."}
{"id": "2369", "text": "Despite vaccines and antiviral substances influenza still causes significant morbidity and mortality world wide .", "annotated_text": "Despite vaccines and antiviral substances influenza still causes significant morbidity and mortality world wide ."}
{"id": "2370", "text": "Better understanding of the molecular mechanisms of influenza virus replication , pathogenesis and host immune responses is required for the development of more efficient means of prevention and treatment of influenza .", "annotated_text": "Better understanding of the molecular mechanisms of influenza virus replication , pathogenesis and host immune responses is required for the development of more efficient means of prevention and treatment of influenza ."}
{"id": "2371", "text": "Influenza A virus , which replicates in epithelial cells and leukocytes , regulates host cell transcriptional and translational systems and activates , as well as downregulates apoptotic pathways .", "annotated_text": "Influenza A virus , which replicates in <cell_type>epithelial cells</cell_type> and <cell_type>leukocytes</cell_type> , regulates host cell transcriptional and translational systems and activates , as well as downregulates apoptotic pathways ."}
{"id": "2372", "text": "Influenza A virus infection results in the production of chemotactic ( RANTES , MIP-1 alpha , MCP-1 , MCP-3 , and IP-10 ) , pro-inflammatory ( IL-1 beta , IL-6 , IL-18 , and TNF-alpha ) , and antiviral ( IFN-alpha/beta ) cytokines .", "annotated_text": "Influenza A virus infection results in the production of chemotactic ( <protein>RANTES</protein> , <protein>MIP-1 alpha</protein> , <protein>MCP-1</protein> , <protein>MCP-3</protein> , and <protein>IP-10</protein> ) , pro-inflammatory ( <protein>IL-1 beta</protein> , <protein>IL-6</protein> , <protein>IL-18</protein> , and <protein>TNF-alpha</protein> ) , and <protein>antiviral ( IFN-alpha/beta ) cytokines</protein> ."}
{"id": "2373", "text": "Cytokine gene expression is associated with the activation of NF-kappa B , AP-1 , STAT and IRF signal transducing molecules in influenza A virus-infected cells .", "annotated_text": "Cytokine gene expression is associated with the activation of <protein>NF-kappa B</protein> , <protein>AP-1</protein> , <protein>STAT</protein> and <protein>IRF signal transducing molecules</protein> in influenza A virus-infected cells ."}
{"id": "2374", "text": "In addition of upregulating cytokine gene expression , influenza A virus infection activates caspase-1 enzyme , which is involved in the proteolytic processing of proIL-1 beta and proIL-18 into their biologically active forms .", "annotated_text": "In addition of upregulating <dna>cytokine gene</dna> expression , influenza A virus infection activates <protein>caspase-1 enzyme</protein> , which is involved in the proteolytic processing of <protein>proIL-1 beta</protein> and <protein>proIL-18</protein> into their biologically active forms ."}
{"id": "2375", "text": "Influenza A virus-induced IFN-alpha/beta is essential in host 's antiviral defence by activating the expression of antiviral Mx , PKR and oligoadenylate synthetase genes .", "annotated_text": "Influenza A virus-induced <protein>IFN-alpha/beta</protein> is essential in host 's antiviral defence by activating the expression of <dna>antiviral Mx</dna> , <dna>PKR and oligoadenylate synthetase genes</dna> ."}
{"id": "2376", "text": "IFN-alpha/beta also prolongs T cell survival , upregulates IL-12 and IL-18 receptor gene expression and together with IL-18 stimulates NK and T cell IFN-gamma production and the development of Th1-type immune response .", "annotated_text": "<protein>IFN-alpha/beta</protein> also prolongs T cell survival , upregulates IL-12 and IL-18 receptor gene expression and together with <protein>IL-18</protein> stimulates <cell_type>NK and T cell</cell_type> IFN-gamma production and the development of Th1-type immune response ."}
{"id": "2377", "text": "Comparison of hprt and lacI mutant frequency with DNA adduct formation in N-hydroxy-2-acetylaminofluorene-treated Big Blue rats .", "annotated_text": "Comparison of hprt and lacI mutant frequency with DNA adduct formation in N-hydroxy-2-acetylaminofluorene-treated Big Blue rats ."}
{"id": "2378", "text": "N-Hydroxy-2-acetylaminofluorene ( N-OH-AAF ) is the proximate carcinogenic metabolite of the powerful rat liver carcinogen 2-acetylaminofluorene .", "annotated_text": "N-Hydroxy-2-acetylaminofluorene ( N-OH-AAF ) is the proximate carcinogenic metabolite of the powerful rat liver carcinogen 2-acetylaminofluorene ."}
{"id": "2379", "text": "In this study , transgenic Big Blue ( R ) rats were used to examine the relationship between in vivo mutagenicity and DNA adduct formation by N-OH-AAF in the target liver compared with that in nontarget tissues .", "annotated_text": "In this study , transgenic Big Blue ( R ) rats were used to examine the relationship between in vivo mutagenicity and DNA adduct formation by N-OH-AAF in the target liver compared with that in nontarget tissues ."}
{"id": "2380", "text": "Male rats were given one , two , or four doses of 25 mg N-OH-AAF/kg body weight by i.p. injection at 4-day intervals , and groups of treated and control rats were euthanized up to 10 weeks after beginning the dosing .", "annotated_text": "Male rats were given one , two , or four doses of 25 mg N-OH-AAF/kg body weight by i.p. injection at 4-day intervals , and groups of treated and control rats were euthanized up to 10 weeks after beginning the dosing ."}
{"id": "2381", "text": "Mutant frequencies were measured in the spleen lymphocyte hprt gene , and lacI mutant frequencies were determined in the liver and spleen lymphocytes .", "annotated_text": "Mutant frequencies were measured in the <dna>spleen lymphocyte hprt gene</dna> , and lacI mutant frequencies were determined in the liver and spleen <cell_type>lymphocytes</cell_type> ."}
{"id": "2382", "text": "At 6 weeks after beginning the dosing , the hprt mutant frequency in spleen lymphocytes from the four-dose group was 16.5 x 10 ( -6 ) compared with 3.2 x 10 ( -6 ) in control animals .", "annotated_text": "At 6 weeks after beginning the dosing , the hprt mutant frequency in <cell_type>spleen lymphocytes</cell_type> from the four-dose group was 16.5 x 10 ( -6 ) compared with 3.2 x 10 ( -6 ) in control animals ."}
{"id": "2383", "text": "Also at 6 weeks , rats given one , two , or four doses of N-OH-AAF had lacI mutant frequencies in the liver of 97.6 , 155.6 , and 406.8 x 10 ( -6 ) , respectively , compared with a control frequency of 25.7 x 10 ( -6 ) ; rats given four doses had lacI mutant frequencies in spleen lymphocytes of 55.8 x 10 ( -6 ) compared with a control frequency of 20.4 x 10 ( -6 ) .", "annotated_text": "Also at 6 weeks , rats given one , two , or four doses of N-OH-AAF had lacI mutant frequencies in the liver of 97.6 , 155.6 , and 406.8 x 10 ( -6 ) , respectively , compared with a control frequency of 25.7 x 10 ( -6 ) ; rats given four doses had lacI mutant frequencies in <cell_type>spleen lymphocytes</cell_type> of 55.8 x 10 ( -6 ) compared with a control frequency of 20.4 x 10 ( -6 ) ."}
{"id": "2384", "text": "Additional rats were evaluated for DNA adduct formation in the liver , spleen lymphocytes , and bone marrow by ( 32 ) P-postlabeling .", "annotated_text": "Additional rats were evaluated for DNA adduct formation in the liver , <cell_type>spleen lymphocytes</cell_type> , and bone marrow by ( 32 ) P-postlabeling ."}
{"id": "2385", "text": "Adduct analysis was conducted 1 day after one , two , and four treatments with N-OH-AAF , 5 days after one treatment , and 9 days after two treatments .", "annotated_text": "Adduct analysis was conducted 1 day after one , two , and four treatments with N-OH-AAF , 5 days after one treatment , and 9 days after two treatments ."}
{"id": "2386", "text": "N- ( Deoxyguanosin-8-yl ) -2-aminofluorene was the major DNA adduct identified in all the tissues examined .", "annotated_text": "N- ( Deoxyguanosin-8-yl ) -2-aminofluorene was the major DNA adduct identified in all the tissues examined ."}
{"id": "2387", "text": "Adduct concentrations increased with total dose to maximum values in samples taken 1 day after two doses , and remained essentially the same after four doses .", "annotated_text": "Adduct concentrations increased with total dose to maximum values in samples taken 1 day after two doses , and remained essentially the same after four doses ."}
{"id": "2388", "text": "In samples taken after four doses , adduct levels were 103 , 28 , and 7 fmol/microg of DNA in liver , spleen lymphocytes , and bone marrow , respectively .", "annotated_text": "In samples taken after four doses , adduct levels were 103 , 28 , and 7 fmol/microg of DNA in liver , <cell_type>spleen lymphocytes</cell_type> , and bone marrow , respectively ."}
{"id": "2389", "text": "The results indicate that the extent of both DNA adduct formation and mutant induction correlates with the organ specificity for N-OH-AAF carcinogenesis in the rat .", "annotated_text": "The results indicate that the extent of both DNA adduct formation and mutant induction correlates with the organ specificity for N-OH-AAF carcinogenesis in the rat ."}
{"id": "2390", "text": "Environ. Mol. Mutagen. 37 : 195-202 , 2001 .", "annotated_text": "Environ. Mol. Mutagen. 37 : 195-202 , 2001 ."}
{"id": "2391", "text": "Published 2001 Wiley-Liss , Inc .", "annotated_text": "Published 2001 Wiley-Liss , Inc ."}
{"id": "2392", "text": "Expression of Mad1 in T cells leads to reduced thymic cellularity and impaired mitogen-induced proliferation .", "annotated_text": "Expression of <protein>Mad1</protein> in <cell_type>T cells</cell_type> leads to reduced thymic cellularity and impaired mitogen-induced proliferation ."}
{"id": "2393", "text": "To investigate Mad1 function in vivo , transgenic mice were generated that express a Mad1 transgene in T lineage cells under the control of the proximal lck promoter .", "annotated_text": "To investigate <protein>Mad1</protein> function in vivo , transgenic mice were generated that express a <dna>Mad1 transgene</dna> in <cell_type>T lineage cells</cell_type> under the control of the <dna>proximal lck promoter</dna> ."}
{"id": "2394", "text": "Thymus size in lck-Mad1 transgenic mice is drastically reduced although representation of the various thymocyte sub populations appears normal .", "annotated_text": "Thymus size in lck-Mad1 transgenic mice is drastically reduced although representation of the various <cell_type>thymocyte sub populations</cell_type> appears normal ."}
{"id": "2395", "text": "To investigate more closely any effects of Mad1 expression on thymocytes , we examined thymic selection using MHC class I-restricted H-Y-TCR transgenic mice .", "annotated_text": "To investigate more closely any effects of Mad1 expression on <cell_type>thymocytes</cell_type> , we examined thymic selection using MHC class I-restricted H-Y-TCR transgenic mice ."}
{"id": "2396", "text": "Mad1 expression in vivo reduces the efficiency of positive selection .", "annotated_text": "Mad1 expression in vivo reduces the efficiency of positive selection ."}
{"id": "2397", "text": "Furthermore , thymocytes and splenic T cells from lck-Mad1 transgenic mice display a profound proliferative defect in response to activation with either PMA/Ionomycin or immobilized anti-CD3/CD28 antibody .", "annotated_text": "Furthermore , <cell_type>thymocytes</cell_type> and <cell_type>splenic T cells</cell_type> from lck-Mad1 transgenic mice display a profound proliferative defect in response to activation with either PMA/Ionomycin or <protein>immobilized anti-CD3/CD28 antibody</protein> ."}
{"id": "2398", "text": "This proliferative defect is not reversed by addition of exogenous IL-2 and is p53-independent .", "annotated_text": "This proliferative defect is not reversed by addition of <protein>exogenous IL-2</protein> and is p53-independent ."}
{"id": "2399", "text": "The growth inhibition caused by Mad1 is overcome by expression of active c-Myc .", "annotated_text": "The growth inhibition caused by <protein>Mad1</protein> is overcome by expression of <protein>active c-Myc</protein> ."}
{"id": "2400", "text": "Differential requirement for the transcription factor PU.1 in the generation of natural killer cells versus B and T cells .", "annotated_text": "Differential requirement for the <protein>transcription factor PU.1</protein> in the generation of <cell_type>natural killer cells</cell_type> versus <cell_type>B and T cells</cell_type> ."}
{"id": "2401", "text": "PU.1 is a member of the Ets family of transcription factors required for the development of various lymphoid and myeloid cell lineages , but its role in natural killer ( NK ) cell development is not known .", "annotated_text": "<protein>PU.1</protein> is a member of the <protein>Ets family of transcription factors</protein> required for the development of various <cell_line>lymphoid and myeloid cell lineages</cell_line> , but its role in <cell_type>natural killer ( NK ) cell</cell_type> development is not known ."}
{"id": "2402", "text": "The study shows that PU.1 is expressed in NK cells and that , on cell transfer into alymphoid Rag2/gammac ( -/- ) mice , hematopoietic progenitors of PU.1 ( -/- ) fetal liver cells could generate functional NK cells but not B or T cells .", "annotated_text": "The study shows that <protein>PU.1</protein> is expressed in <cell_type>NK cells</cell_type> and that , on cell transfer into alymphoid Rag2/gammac ( -/- ) mice , <cell_type>hematopoietic progenitors</cell_type> of <cell_type>PU.1 ( -/- ) fetal liver cells</cell_type> could generate functional <cell_type>NK cells</cell_type> but not <cell_type>B or T cells</cell_type> ."}
{"id": "2403", "text": "Nevertheless , the numbers of bone marrow NK cell precursors and splenic mature NK cells were reduced compared to controls .", "annotated_text": "Nevertheless , the numbers of <cell_type>bone marrow NK cell precursors</cell_type> and <cell_type>splenic mature NK cells</cell_type> were reduced compared to controls ."}
{"id": "2404", "text": "Moreover , PU.1 ( -/- ) NK cells displayed reduced expression of the receptors for stem cell factor and interleukin ( IL ) -7 , suggesting a nonredundant role for PU.1 in regulating the expression of these cytokine receptor genes during NK cell development .", "annotated_text": "Moreover , <cell_type>PU.1 ( -/- ) NK cells</cell_type> displayed reduced expression of the receptors for <protein>stem cell factor</protein> and <protein>interleukin ( IL ) -7</protein> , suggesting a nonredundant role for <protein>PU.1</protein> in regulating the expression of these <dna>cytokine receptor genes</dna> during NK cell development ."}
{"id": "2405", "text": "PU.1 ( -/- ) NK cells also showed defective expression of inhibitory and activating members of the Ly49 family and failed to proliferate in response to IL-2 and IL-12 .", "annotated_text": "<cell_type>PU.1 ( -/- ) NK cells</cell_type> also showed defective expression of inhibitory and activating members of the <protein>Ly49 family</protein> and failed to proliferate in response to <protein>IL-2</protein> and <protein>IL-12</protein> ."}
{"id": "2406", "text": "Thus , despite the less stringent requirement for PU.1 in NK cell development compared to B and T cells , PU.1 regulates NK cell differentiation and homeostasis .", "annotated_text": "Thus , despite the less stringent requirement for <protein>PU.1</protein> in NK cell development compared to <cell_type>B and T cells</cell_type> , <protein>PU.1</protein> regulates NK cell differentiation and homeostasis ."}
{"id": "2407", "text": "Benzene-extracted components are important for the major activity of diesel exhaust particles : effect on interleukin-8 gene expression in human bronchial epithelial cells .", "annotated_text": "Benzene-extracted components are important for the major activity of diesel exhaust particles : effect on <dna>interleukin-8 gene</dna> expression in <cell_type>human bronchial epithelial cells</cell_type> ."}
{"id": "2408", "text": "Epidemiologic and experimental studies suggest that diesel exhaust particles ( DEPs ) may be related to increasing respiratory mortality and morbidity .", "annotated_text": "Epidemiologic and experimental studies suggest that diesel exhaust particles ( DEPs ) may be related to increasing respiratory mortality and morbidity ."}
{"id": "2409", "text": "We have shown that DEPs augmented the production of inflammatory cytokines by human airway epithelial cells in vitro .", "annotated_text": "We have shown that DEPs augmented the production of <protein>inflammatory cytokines</protein> by <cell_type>human airway epithelial cells</cell_type> in vitro ."}
{"id": "2410", "text": "To better understand the mechanisms of their proinflammatory activities , we studied the effects of several components extracted from DEPs on interleukin ( IL ) -8 expression in human bronchial epithelial cell line BEAS-2B and normal human airway epithelial cells obtained from very peripheral airways by an ultrathin bronchoscope .", "annotated_text": "To better understand the mechanisms of their proinflammatory activities , we studied the effects of several components extracted from DEPs on interleukin ( IL ) -8 expression in <cell_line>human bronchial epithelial cell line BEAS-2B</cell_line> and <cell_type>normal human airway epithelial cells</cell_type> obtained from very peripheral airways by an ultrathin bronchoscope ."}
{"id": "2411", "text": "We used several agents active on signal transduction pathways in cytokine expression , such as the protein kinase C inhibitor staurosporin , antioxidant agents including N-acetyl cysteine ( NAC ) and pyrrolidine dithiocarbamate ( PDTC ) , and p38 mitogen-activated protein kinase ( MAPK ) inhibitor SB203580 .", "annotated_text": "We used several agents active on signal transduction pathways in cytokine expression , such as the protein kinase C inhibitor staurosporin , antioxidant agents including N-acetyl cysteine ( NAC ) and pyrrolidine dithiocarbamate ( PDTC ) , and <protein>p38 mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) inhibitor SB203580 ."}
{"id": "2412", "text": "Benzene-extracted components showed effects mimicking DEPs on IL-8 gene expression , release of several cytokines ( IL-8 ; granulocyte macrophage colony-stimulating factor ; and regulated on activation , normal T cells expressed and secreted ) and nuclear factor ( NF ) -kappa B activation .", "annotated_text": "Benzene-extracted components showed effects mimicking DEPs on IL-8 gene expression , release of several <protein>cytokines</protein> ( <protein>IL-8</protein> ; <protein>granulocyte macrophage colony-stimulating factor</protein> ; and regulated on activation , <cell_type>normal T cells</cell_type> expressed and secreted ) and nuclear factor ( NF ) -kappa B activation ."}
{"id": "2413", "text": "We also found that NAC , PDTC , and SB203580 suppressed the activities of DEPs and their benzene extracts , suggesting the roles of oxidants-mediated NF-kappa B activation and p38MAPK pathways .", "annotated_text": "We also found that NAC , PDTC , and SB203580 suppressed the activities of DEPs and their benzene extracts , suggesting the roles of oxidants-mediated NF-kappa B activation and <protein>p38MAPK</protein> pathways ."}
{"id": "2414", "text": "Finally , benzo [ a ] pyrene , one of the important compounds included in the benzene component , replicated the activities shown by DEPs .", "annotated_text": "Finally , benzo [ a ] pyrene , one of the important compounds included in the benzene component , replicated the activities shown by DEPs ."}
{"id": "2415", "text": "The nuclear receptor PPAR gamma is expressed by mouse T lymphocytes and PPAR gamma agonists induce apoptosis .", "annotated_text": "The <protein>nuclear receptor PPAR gamma</protein> is expressed by <cell_type>mouse T lymphocytes</cell_type> and PPAR gamma agonists induce apoptosis ."}
{"id": "2416", "text": "Peroxisome proliferator-activated receptor ( PPAR ) -gamma is a nuclear hormone receptor that serves as a trans factor to regulate lipid metabolism .", "annotated_text": "<protein>Peroxisome proliferator-activated receptor ( PPAR ) -gamma</protein> is a <protein>nuclear hormone receptor</protein> that serves as a trans factor to regulate lipid metabolism ."}
{"id": "2417", "text": "Intense interest is focused on PPAR-gamma and its ligands owing to its putative role in adipocyte differentiation .", "annotated_text": "Intense interest is focused on <protein>PPAR-gamma</protein> and its ligands owing to its putative role in adipocyte differentiation ."}
{"id": "2418", "text": "Little is known , however , about the functions of PPAR-gamma in the immune system , especially in T lymphocytes .", "annotated_text": "Little is known , however , about the functions of <protein>PPAR-gamma</protein> in the immune system , especially in <cell_type>T lymphocytes</cell_type> ."}
{"id": "2419", "text": "We demonstrate that both naive and activated ovalbumin-specific T cells from DO11.10-transgenic mice express PPAR-gamma mRNA and protein .", "annotated_text": "We demonstrate that both <cell_type>naive and activated ovalbumin-specific T cells</cell_type> from DO11.10-transgenic mice express <rna>PPAR-gamma</rna> mRNA and protein ."}
{"id": "2420", "text": "In order to determine the function of PPAR-gamma , T cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin or antigen and antigen-presenting cells .", "annotated_text": "In order to determine the function of <protein>PPAR-gamma</protein> , <cell_type>T cells</cell_type> were stimulated with phorbol 12-myristate 13-acetate and ionomycin or antigen and <cell_type>antigen-presenting cells</cell_type> ."}
{"id": "2421", "text": "Simultaneous exposure to PPAR-gamma ligands ( e.g. 15-deoxy-Delta ( 12 , 14 ) -prostaglandin J ( 2 ) , troglitazone ) showed drastic inhibition of proliferation and significant decreases in cell viability .", "annotated_text": "Simultaneous exposure to PPAR-gamma ligands ( e.g. 15-deoxy-Delta ( 12 , 14 ) -prostaglandin J ( 2 ) , troglitazone ) showed drastic inhibition of proliferation and significant decreases in cell viability ."}
{"id": "2422", "text": "The decrease in cell viability was due to apoptosis of the T lymphocytes , and occurred only when cells were treated with PPAR-gamma , and not PPAR-alpha agonists , revealing specificity of this response for PPAR-gamma .", "annotated_text": "The decrease in cell viability was due to apoptosis of the <cell_type>T lymphocytes</cell_type> , and occurred only when cells were treated with <protein>PPAR-gamma</protein> , and not PPAR-alpha agonists , revealing specificity of this response for <protein>PPAR-gamma</protein> ."}
{"id": "2423", "text": "These observations suggest that PPAR-gamma agonists play an important role in regulating T cell-mediated immune responses by inducing apoptosis .", "annotated_text": "These observations suggest that PPAR-gamma agonists play an important role in regulating T cell-mediated immune responses by inducing apoptosis ."}
{"id": "2424", "text": "T cell death via PPAR-gamma ligation may act as a potent anti-inflammatory signal in the immune system , and ligands could possibly be used to control disorders in which excessive inflammation occurs .", "annotated_text": "T cell death via PPAR-gamma ligation may act as a potent anti-inflammatory signal in the immune system , and ligands could possibly be used to control disorders in which excessive inflammation occurs ."}
{"id": "2425", "text": "Suppression of lung inflammation in rats by prevention of NF-kappaB activation in the liver .", "annotated_text": "Suppression of lung inflammation in rats by prevention of NF-kappaB activation in the liver ."}
{"id": "2426", "text": "Activation of NF-kappaB and production of NF-kappaB -dependent chemokines are thought to be involved in the pathogenesis of neutrophilic lung inflammation .", "annotated_text": "Activation of <protein>NF-kappaB</protein> and production of <protein>NF-kappaB</protein> -dependent <protein>chemokines</protein> are thought to be involved in the pathogenesis of neutrophilic lung inflammation ."}
{"id": "2427", "text": "Calpain-1 inhibitor ( CI-1 ) blocks activation of NF-kappaB by preventing proteolysis of the inhibitory protein IkappaB-alpha by the ubiquitin/proteasome pathway .", "annotated_text": "Calpain-1 inhibitor ( CI-1 ) blocks activation of <protein>NF-kappaB</protein> by preventing proteolysis of the inhibitory protein <protein>IkappaB-alpha</protein> by the ubiquitin/proteasome pathway ."}
{"id": "2428", "text": "We hypothesized that inhibition of proteasome function with CI-1 would block NF-kappaB activation in vivo after intraperitoneal ( i.p. ) treatment with bacterial lipopolysaccharide ( LPS ) , and that NF-kappaB inhibition would be associated with suppression of chemokine gene expression and attenuation of neutrophilic alveolitis .", "annotated_text": "We hypothesized that inhibition of proteasome function with CI-1 would block NF-kappaB activation in vivo after intraperitoneal ( i.p. ) treatment with bacterial lipopolysaccharide ( LPS ) , and that NF-kappaB inhibition would be associated with suppression of chemokine gene expression and attenuation of neutrophilic alveolitis ."}
{"id": "2429", "text": "We treated rats with a single i.p. injection of CI-1 ( 10 mg/kg ) two hours prior to i.p. LPS ( 7 mg/kg ) .", "annotated_text": "We treated rats with a single i.p. injection of CI-1 ( 10 mg/kg ) two hours prior to i.p. LPS ( 7 mg/kg ) ."}
{"id": "2430", "text": "Treatment with Cl-1 prevented degradation of IkappaB-alpha and activation of NF-kappaB in the liver in response to LPS ; however , Cl-1 treatment had no detected effect on NF-kappaB activation in lung tissue .", "annotated_text": "Treatment with Cl-1 prevented degradation of <protein>IkappaB-alpha</protein> and activation of <protein>NF-kappaB</protein> in the liver in response to LPS ; however , Cl-1 treatment had no detected effect on NF-kappaB activation in lung tissue ."}
{"id": "2431", "text": "CI-1 treatment prior to LPS resulted in 40 % lower MIP-2 concentration in lung lavage fluid compared to rats treated with vehicle prior to LPS ( 502 +/- 112 pg/ml vs. 859 +/-144 pg/ml , P < 0.05 ) .", "annotated_text": "CI-1 treatment prior to LPS resulted in 40 % lower MIP-2 concentration in lung lavage fluid compared to rats treated with vehicle prior to LPS ( 502 +/- 112 pg/ml vs. 859 +/-144 pg/ml , P < 0.05 ) ."}
{"id": "2432", "text": "In addition , CI-1 treatment substantially inhibited LPS-induced neutrophilic alveolitis ( 2.7+ /- 1.2 x 10 ( 5 ) vs. 43.7 +/- 12.2 x 10 ( 5 ) lung lavage neutrophils , P < 0.01 ) .", "annotated_text": "In addition , CI-1 treatment substantially inhibited LPS-induced neutrophilic alveolitis ( 2.7+ /- 1.2 x 10 ( 5 ) vs. 43.7 +/- 12.2 x 10 ( 5 ) <cell_type>lung lavage neutrophils</cell_type> , P < 0.01 ) ."}
{"id": "2433", "text": "These data indicate that NF-kappaB inhibition in the liver can alter lung inflammation induced by systemic LPS treatment and suggest that a liver-lung interaction contributes to the inflammatory response of the lung .", "annotated_text": "These data indicate that NF-kappaB inhibition in the liver can alter lung inflammation induced by systemic LPS treatment and suggest that a liver-lung interaction contributes to the inflammatory response of the lung ."}
{"id": "2434", "text": "Notch1 regulates maturation of CD4+ and CD8+ thymocytes by modulating TCR signal strength .", "annotated_text": "<protein>Notch1</protein> regulates maturation of <cell_type>CD4+ and CD8+ thymocytes</cell_type> by modulating TCR signal strength ."}
{"id": "2435", "text": "Notch signaling regulates cell fate decisions in multiple lineages .", "annotated_text": "Notch signaling regulates cell fate decisions in multiple lineages ."}
{"id": "2436", "text": "We demonstrate in this report that retroviral expression of activated Notch1 in mouse thymocytes abrogates differentiation of immature CD4+CD8+ thymocytes into both CD4 and CD8 mature single-positive T cells .", "annotated_text": "We demonstrate in this report that retroviral expression of activated <protein>Notch1</protein> in <cell_type>mouse thymocytes</cell_type> abrogates differentiation of <cell_type>immature CD4+CD8+ thymocytes</cell_type> into both <cell_type>CD4 and CD8 mature single-positive T cells</cell_type> ."}
{"id": "2437", "text": "The ability of Notch1 to inhibit T cell development was observed in vitro and in vivo with both normal and TCR transgenic thymocytes .", "annotated_text": "The ability of <protein>Notch1</protein> to inhibit T cell development was observed in vitro and in vivo with both <cell_type>normal and TCR transgenic thymocytes</cell_type> ."}
{"id": "2438", "text": "Notch1 -mediated developmental arrest was dose dependent and was associated with impaired thymocyte responses to TCR stimulation .", "annotated_text": "<protein>Notch1</protein> -mediated developmental arrest was dose dependent and was associated with impaired thymocyte responses to TCR stimulation ."}
{"id": "2439", "text": "Notch1 also inhibited TCR-mediated signaling in Jurkat T cells .", "annotated_text": "<protein>Notch1</protein> also inhibited TCR-mediated signaling in <cell_line>Jurkat T cells</cell_line> ."}
{"id": "2440", "text": "These data indicate that constitutively active Notch1 abrogates CD4+ and CD8+ maturation by interfering with TCR signal strength and provide an explanation for the physiological regulation of Notch expression during thymocyte development .", "annotated_text": "These data indicate that constitutively active <protein>Notch1</protein> abrogates CD4+ and CD8+ maturation by interfering with TCR signal strength and provide an explanation for the physiological regulation of Notch expression during thymocyte development ."}
{"id": "2441", "text": "Expression of SART3 antigen and induction of CTLs by SART3-derived peptides in breast cancer patients .", "annotated_text": "Expression of <protein>SART3 antigen</protein> and induction of <cell_type>CTLs</cell_type> by SART3-derived peptides in breast cancer patients ."}
{"id": "2442", "text": "We recently reported the SART3 tumour-rejection antigen as possessing tumour epitopes capable of inducing HLA-class I-restricted cytotoxic T lymphocytes ( CTLs ) .", "annotated_text": "We recently reported the <protein>SART3 tumour-rejection antigen</protein> as possessing tumour epitopes capable of inducing <cell_type>HLA-class I-restricted cytotoxic T lymphocytes</cell_type> ( <cell_type>CTLs</cell_type> ) ."}
{"id": "2443", "text": "This study investigated expression of the SART3 antigen in breast cancer to explore an appropriate molecule for use in specific immunotherapy of breast cancer patients .", "annotated_text": "This study investigated expression of the <protein>SART3 antigen</protein> in breast cancer to explore an appropriate molecule for use in specific immunotherapy of breast cancer patients ."}
{"id": "2444", "text": "The SART3 antigen was detected in all of the breast cancer cell lines tested , 30 of 40 ( 75 % ) breast cancer tissue samples , and 0 of 3 non-tumourous breast tissue samples .", "annotated_text": "The <protein>SART3 antigen</protein> was detected in all of the <cell_line>breast cancer cell lines</cell_line> tested , 30 of 40 ( 75 % ) breast cancer tissue samples , and 0 of 3 non-tumourous breast tissue samples ."}
{"id": "2445", "text": "SART3 derived peptides at positions 109-118 and 315-323 induced HLA-A24 restricted CTLs that reacted to breast cancer cells from the peripheral blood mononuclear cells ( PBMCs ) of breast cancer patients .", "annotated_text": "SART3 derived peptides at <dna>positions 109-118 and 315-323</dna> induced HLA-A24 restricted <cell_type>CTLs</cell_type> that reacted to <cell_type>breast cancer cells</cell_type> from the <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMCs</cell_type> ) of breast cancer patients ."}
{"id": "2446", "text": "Therefore , the SART3 antigen and its peptides could be an appropriate molecule for use in specific immunotherapy of the majority of HLA-A24-positive breast cancer patients", "annotated_text": "Therefore , the <protein>SART3 antigen</protein> and its peptides could be an appropriate molecule for use in specific immunotherapy of the majority of HLA-A24-positive breast cancer patients"}
{"id": "2447", "text": "Autostimulation of the Epstein-Barr virus BRLF1 promoter is mediated through consensus Sp1 and Sp3 binding sites .", "annotated_text": "Autostimulation of the Epstein-Barr virus <dna>BRLF1 promoter</dna> is mediated through consensus <dna>Sp1 and Sp3 binding sites</dna> ."}
{"id": "2448", "text": "As an essential step in the lytic cascade , the Rta homologues of gammaherpesviruses all activate their own expression .", "annotated_text": "As an essential step in the lytic cascade , the Rta homologues of gammaherpesviruses all activate their own expression ."}
{"id": "2449", "text": "Consistent with this biologic function , the Epstein-Barr virus ( EBV ) Rta protein powerfully stimulates the promoter of its own gene , Rp , in EBV-positive B cells in transient-transfection reporter-based assays .", "annotated_text": "Consistent with this biologic function , the Epstein-Barr virus ( EBV ) <protein>Rta protein</protein> powerfully stimulates the <dna>promoter</dna> of its own gene , <dna>Rp</dna> , in <cell_type>EBV-positive B cells</cell_type> in transient-transfection reporter-based assays ."}
{"id": "2450", "text": "We analyzed the activity of RpCAT in response to Rta by deletional and site-directed mutagenesis .", "annotated_text": "We analyzed the activity of <dna>RpCAT</dna> in response to <protein>Rta</protein> by deletional and site-directed mutagenesis ."}
{"id": "2451", "text": "Two cognate Sp1 binding sites located at -279 and -45 relative to the transcriptional start site proved crucial for Rta-mediated activation .", "annotated_text": "Two <dna>cognate Sp1 binding sites</dna> located at -279 and -45 relative to the <dna>transcriptional start site</dna> proved crucial for Rta-mediated activation ."}
{"id": "2452", "text": "Previously described binding sites for the cellular transcription factor Zif268 and the viral transactivator ZEBRA were found to be dispensable for activation of RpCAT by Rta .", "annotated_text": "Previously described binding sites for the cellular <protein>transcription factor Zif268</protein> and the <protein>viral transactivator ZEBRA</protein> were found to be dispensable for activation of <dna>RpCAT</dna> by <protein>Rta</protein> ."}
{"id": "2453", "text": "Gel shift analysis , using extracts of B cells in latency or induced into the lytic cycle , identified Sp1 and Sp3 as the predominant cellular proteins bound to Rp near -45 .", "annotated_text": "Gel shift analysis , using extracts of <cell_type>B cells</cell_type> in latency or induced into the lytic cycle , identified <protein>Sp1</protein> and <protein>Sp3</protein> as the predominant <protein>cellular proteins</protein> bound to <dna>Rp</dna> near -45 ."}
{"id": "2454", "text": "During the lytic cycle , ZEBRA bound Rp near the Sp1/Sp3 site .", "annotated_text": "During the lytic cycle , <protein>ZEBRA</protein> bound <dna>Rp</dna> near the <dna>Sp1/Sp3 site</dna> ."}
{"id": "2455", "text": "The binding of Sp1 and Sp3 to Rp correlated with the reporter activities in the mutagenesis study , establishing a direct link between transcriptional activation of Rp by Rta and DNA binding by Sp1 and/or Sp3 .", "annotated_text": "The binding of <protein>Sp1</protein> and <protein>Sp3</protein> to <dna>Rp</dna> correlated with the reporter activities in the mutagenesis study , establishing a direct link between transcriptional activation of <dna>Rp</dna> by <protein>Rta</protein> and DNA binding by <protein>Sp1</protein> and/or <protein>Sp3</protein> ."}
{"id": "2456", "text": "The relative abundance or functional state of the cellular Sp1 and Sp3 transcription factors may be altered in response to stimuli that induce the BRLF1 promoter and thereby contribute to the activation of the viral lytic cycle .", "annotated_text": "The relative abundance or functional state of the cellular <protein>Sp1</protein> and <protein>Sp3</protein> <protein>transcription factors</protein> may be altered in response to stimuli that induce the <dna>BRLF1 promoter</dna> and thereby contribute to the activation of the viral lytic cycle ."}
{"id": "2457", "text": "Gene transfer of antisense hypoxia inducible factor-1 alpha enhances the therapeutic efficacy of cancer immunotherapy .", "annotated_text": "Gene transfer of antisense <protein>hypoxia inducible factor-1 alpha</protein> enhances the therapeutic efficacy of cancer immunotherapy ."}
{"id": "2458", "text": "Solid tumors meet their demands for nascent blood vessels and increased glycolysis , to combat hypoxia , by activating multiple genes involved in angiogenesis and glucose metabolism .", "annotated_text": "Solid tumors meet their demands for nascent blood vessels and increased glycolysis , to combat hypoxia , by activating multiple genes involved in angiogenesis and glucose metabolism ."}
{"id": "2459", "text": "Hypoxia inducible factor-1 ( HIF-1 ) is a constitutively expressed basic helix-loop-helix transcription factor , formed by the assembly of HIF-1alpha and HIF-1beta ( Arnt ) , that is stablized in response to hypoxia , and rapidly degraded under normoxic conditions .", "annotated_text": "<protein>Hypoxia inducible factor-1</protein> ( <protein>HIF-1</protein> ) is a constitutively expressed basic <protein>helix-loop-helix transcription factor</protein> , formed by the assembly of <protein>HIF-1alpha</protein> and <protein>HIF-1beta</protein> ( <protein>Arnt</protein> ) , that is stablized in response to hypoxia , and rapidly degraded under normoxic conditions ."}
{"id": "2460", "text": "It activates the transcription of genes important for maintaining oxygen homeostasis .", "annotated_text": "It activates the transcription of genes important for maintaining oxygen homeostasis ."}
{"id": "2461", "text": "Here , we demonstrate that engineered down-regulation of HIF-1alpha by intratumoral gene transfer of an antisense HIF-1alpha plasmid leads to the down-regulation of VEGF , and decreased tumor microvessel density .", "annotated_text": "Here , we demonstrate that engineered down-regulation of <protein>HIF-1alpha</protein> by intratumoral gene transfer of an <dna>antisense HIF-1alpha plasmid</dna> leads to the down-regulation of <dna>VEGF</dna> , and decreased tumor microvessel density ."}
{"id": "2462", "text": "Antisense HIF-1alpha monotherapy resulted in the complete and permanent rejection of small ( 0.1 cm in diameter ) EL-4 tumors , which is unusual for an anti-angiogenic agent where transient suppression of tumor growth is the norm .", "annotated_text": "Antisense HIF-1alpha monotherapy resulted in the complete and permanent rejection of small ( 0.1 cm in diameter ) EL-4 tumors , which is unusual for an anti-angiogenic agent where transient suppression of tumor growth is the norm ."}
{"id": "2463", "text": "It induced NK cell -dependent rejection of tumors , but failed to stimulate systemic T cell -mediated anti-tumor immunity , and synergized with B7-1-mediated immunotherapy to cause the NK cell and CD8 T cell -dependent rejection of larger EL-4 tumors ( 0.4 cm in diameter ) that were refractory to monotherapies .", "annotated_text": "It induced <cell_type>NK cell</cell_type> -dependent rejection of tumors , but failed to stimulate systemic <cell_type>T cell</cell_type> -mediated anti-tumor immunity , and synergized with B7-1-mediated immunotherapy to cause the <cell_type>NK cell</cell_type> and <cell_type>CD8 T cell</cell_type> -dependent rejection of larger EL-4 tumors ( 0.4 cm in diameter ) that were refractory to monotherapies ."}
{"id": "2464", "text": "Mice cured of their tumors by combination therapy resisted a rechallenge with parental tumor cells , indicating systemic antitumor immunity had been achieved .", "annotated_text": "Mice cured of their tumors by combination therapy resisted a rechallenge with <cell_type>parental tumor cells</cell_type> , indicating systemic antitumor immunity had been achieved ."}
{"id": "2465", "text": "In summary , whilst intensive investigations are in progress to target the many HIF-1 effectors , the results herein indicate that blocking hypoxia-inducible pathways and enhancing NK-mediated antitumor immunity by targeting HIF-1 itself may be advantageous , especially when combined with cancer immunotherapy .", "annotated_text": "In summary , whilst intensive investigations are in progress to target the many <protein>HIF-1</protein> effectors , the results herein indicate that blocking hypoxia-inducible pathways and enhancing NK-mediated antitumor immunity by targeting <protein>HIF-1</protein> itself may be advantageous , especially when combined with cancer immunotherapy ."}
{"id": "2466", "text": "Runx2 : a novel oncogenic effector revealed by in vivo complementation and retroviral tagging .", "annotated_text": "<dna>Runx2</dna> : a novel oncogenic effector revealed by in vivo complementation and retroviral tagging ."}
{"id": "2467", "text": "The Runx2 ( Cbfa1 , Pebp2alphaA , Aml3 ) gene was previously identified as a frequent target for transcriptional activation by proviral insertion in T-cell lymphomas of CD2-MYC transgenic mice .", "annotated_text": "The <dna>Runx2</dna> ( <dna>Cbfa1</dna> , <dna>Pebp2alphaA</dna> , <dna>Aml3</dna> ) gene was previously identified as a frequent target for transcriptional activation by proviral insertion in T-cell lymphomas of CD2-MYC transgenic mice ."}
{"id": "2468", "text": "We have recently shown that over-expression of the full-length , most highly expressed Runx2 isoform in the thymus perturbs T-cell development , leads to development of spontaneous lymphomas at low frequency and is strongly synergistic with Myc .", "annotated_text": "We have recently shown that over-expression of the full-length , most highly expressed <dna>Runx2</dna> isoform in the thymus perturbs T-cell development , leads to development of spontaneous lymphomas at low frequency and is strongly synergistic with <protein>Myc</protein> ."}
{"id": "2469", "text": "To gain further insight into the relationship of Runx2 to other lymphomagenic pathways , we tested the effect of combining the CD2-Runx2 transgene either with a Pim1 transgene ( E ( mu ) -Pim1 ) or with the p53 null genotype , as each of these displays independent synergy with Myc .", "annotated_text": "To gain further insight into the relationship of <dna>Runx2</dna> to other lymphomagenic pathways , we tested the effect of combining the <dna>CD2-Runx2 transgene</dna> either with a <dna>Pim1 transgene</dna> ( <dna>E ( mu ) -Pim1</dna> ) or with the <dna>p53</dna> null genotype , as each of these displays independent synergy with <protein>Myc</protein> ."}
{"id": "2470", "text": "In both cases we observed synergistic tumour development .", "annotated_text": "In both cases we observed synergistic tumour development ."}
{"id": "2471", "text": "However , Runx2 appeared to have a dominant effect on the tumour phenotype in each case , with most tumours conforming to the CD3 ( + ) , CD8 ( + ) , CD4 ( +/- ) phenotype seen in CD2-Runx2 mice .", "annotated_text": "However , <protein>Runx2</protein> appeared to have a dominant effect on the tumour phenotype in each case , with most tumours conforming to the CD3 ( + ) , CD8 ( + ) , CD4 ( +/- ) phenotype seen in CD2-Runx2 mice ."}
{"id": "2472", "text": "Neonatal infection of CD2-Runx2 mice with Moloney murine leukaemia virus ( Moloney MLV ) also led to a dramatic acceleration of tumour onset .", "annotated_text": "Neonatal infection of CD2-Runx2 mice with Moloney murine leukaemia virus ( Moloney MLV ) also led to a dramatic acceleration of tumour onset ."}
{"id": "2473", "text": "Analysis of known Moloney MLV target genes in these lymphomas showed a high frequency of rearrangement at c-Myc or N-Myc ( 82 % ) , and a significant number at Pim1 or Pim2 ( 23 % ) , and at Pal1/Gfi1 ( 18 % ) .", "annotated_text": "Analysis of known <dna>Moloney MLV target genes</dna> in these lymphomas showed a high frequency of rearrangement at <dna>c-Myc</dna> or <dna>N-Myc</dna> ( 82 % ) , and a significant number at <dna>Pim1</dna> or <dna>Pim2</dna> ( 23 % ) , and at <dna>Pal1/Gfi1</dna> ( 18 % ) ."}
{"id": "2474", "text": "These results indicate that Runx2 makes a distinct contribution to T-cell lymphoma development which does not coincide with any of the oncogene complementation groups previously identified by retroviral tagging .", "annotated_text": "These results indicate that <protein>Runx2</protein> makes a distinct contribution to T-cell lymphoma development which does not coincide with any of the oncogene complementation groups previously identified by retroviral tagging ."}
{"id": "2475", "text": "The involvement of TNF-alpha -related apoptosis-inducing ligand in the enhanced cytotoxicity of IFN-beta -stimulated human dendritic cells to tumor cells .", "annotated_text": "The involvement of <protein>TNF-alpha</protein> -related apoptosis-inducing ligand in the enhanced cytotoxicity of <protein>IFN-beta</protein> -stimulated <cell_type>human dendritic cells</cell_type> to <cell_type>tumor cells</cell_type> ."}
{"id": "2476", "text": "TNF-alpha -related apoptosis-inducing ligand ( TRAIL ) is characterized by its preferential induction of apoptosis of tumor cells but not normal cells .", "annotated_text": "<protein>TNF-alpha</protein> -related apoptosis-inducing ligand ( TRAIL ) is characterized by its preferential induction of apoptosis of <cell_type>tumor cells</cell_type> but not <cell_type>normal cells</cell_type> ."}
{"id": "2477", "text": "Dendritic cells ( DCs ) , besides their role as APCs , now have been demonstrated to exert cytotoxicity or cytostasis on some tumor cells .", "annotated_text": "<cell_type>Dendritic cells</cell_type> ( <cell_type>DCs</cell_type> ) , besides their role as APCs , now have been demonstrated to exert cytotoxicity or cytostasis on some <cell_type>tumor cells</cell_type> ."}
{"id": "2478", "text": "Here , we report that both human CD34 ( + ) stem cell -derived DCs ( CD34DCs ) and human CD14 ( + ) monocyte -derived DCs ( MoDCs ) express TRAIL and exhibit cytotoxicity to some types of tumor cells partially through TRAIL .", "annotated_text": "Here , we report that both <cell_type>human CD34 ( + ) stem cell</cell_type> -derived <cell_type>DCs</cell_type> ( <cell_type>CD34DCs</cell_type> ) and <cell_type>human CD14 ( + ) monocyte</cell_type> -derived <cell_type>DCs</cell_type> ( <cell_type>MoDCs</cell_type> ) express TRAIL and exhibit cytotoxicity to some types of <cell_type>tumor cells</cell_type> partially through TRAIL ."}
{"id": "2479", "text": "Moderate expression of TRAIL appeared on CD34DCs from the 8th day of culture and was also seen on freshly isolated monocytes .", "annotated_text": "Moderate expression of TRAIL appeared on <cell_type>CD34DCs</cell_type> from the 8th day of culture and was also seen on <cell_type>freshly isolated monocytes</cell_type> ."}
{"id": "2480", "text": "The level of TRAIL expression remained constant until DC maturation .", "annotated_text": "The level of TRAIL expression remained constant until DC maturation ."}
{"id": "2481", "text": "TRAIL expression on immature CD34DCs or MoDCs was greatly up-regulated after IFN-beta stimulation .", "annotated_text": "TRAIL expression on <cell_type>immature CD34DCs</cell_type> or <cell_type>MoDCs</cell_type> was greatly up-regulated after <protein>IFN-beta</protein> stimulation ."}
{"id": "2482", "text": "Moreover , IFN-beta could strikingly enhance the ability of CD34DCs or MoDCs to kill TRAIL-sensitive tumor cells , but LPS did not have such an effect .", "annotated_text": "Moreover , <protein>IFN-beta</protein> could strikingly enhance the ability of <cell_type>CD34DCs</cell_type> or <cell_type>MoDCs</cell_type> to kill TRAIL-sensitive <cell_type>tumor cells</cell_type> , but LPS did not have such an effect ."}
{"id": "2483", "text": "The up-regulation of TRAIL on IFN-beta -stimulated DCs partially contributed to the increased cytotoxicity of DCS : Pretreatment of TRAIL-sensitive tumor cells with caspase-3 inhibitor could significantly increase their resistance to the cytotoxicity of IFN-beta -stimulated DCS : In contrast , NF-kappaB inhibitor could significantly increase the sensitivity of tumor cells to the killing by nonstimulated or LPS-stimulated DCS : Our studies demonstrate that IFN-beta -stimulated DCs are functionally cytotoxic .", "annotated_text": "The up-regulation of TRAIL on <protein>IFN-beta</protein> -stimulated <cell_type>DCs</cell_type> partially contributed to the increased cytotoxicity of <cell_type>DCS</cell_type> : Pretreatment of TRAIL-sensitive <cell_type>tumor cells</cell_type> with caspase-3 inhibitor could significantly increase their resistance to the cytotoxicity of <protein>IFN-beta</protein> -stimulated <cell_type>DCS</cell_type> : In contrast , NF-kappaB inhibitor could significantly increase the sensitivity of <cell_type>tumor cells</cell_type> to the killing by nonstimulated or LPS-stimulated <cell_type>DCS</cell_type> : Our studies demonstrate that <protein>IFN-beta</protein> -stimulated <cell_type>DCs</cell_type> are functionally cytotoxic ."}
{"id": "2484", "text": "Thus , an innate mechanism of DC-mediated antitumor immunity might exist in vivo in which DCs act as effectors to directly kill tumor cells partially via TRAIL .", "annotated_text": "Thus , an innate mechanism of DC-mediated antitumor immunity might exist in vivo in which <cell_type>DCs</cell_type> act as effectors to directly kill <cell_type>tumor cells</cell_type> partially via TRAIL ."}
{"id": "2485", "text": "Subsequently , DCs act as APCs involved in the uptake , processing , and presentation of apoptotic tumor Ags to cross-prime CD8 ( + ) CTL cells .", "annotated_text": "Subsequently , <cell_type>DCs</cell_type> act as APCs involved in the uptake , processing , and presentation of <protein>apoptotic tumor Ags</protein> to cross-prime <cell_type>CD8 ( + ) CTL cells</cell_type> ."}
{"id": "2486", "text": "Tumor cells regulate the lytic activity of tumor-specific cytotoxic t lymphocytes by modulating the inhibitory natural killer receptor function .", "annotated_text": "<cell_type>Tumor cells</cell_type> regulate the lytic activity of <cell_type>tumor-specific cytotoxic t lymphocytes</cell_type> by modulating the inhibitory natural killer receptor function ."}
{"id": "2487", "text": "Tumor-infiltrating p58+ T cells from a renal tumor were specifically expanded in response to tumor cell stimulation and cloned .", "annotated_text": "<cell_type>Tumor-infiltrating p58+ T cells</cell_type> from a renal tumor were specifically expanded in response to tumor cell stimulation and cloned ."}
{"id": "2488", "text": "These p58+ T cells were found to express a memory phenotype and corresponded to clonal TCRBV3 T-cell expansion .", "annotated_text": "These <cell_type>p58+ T cells</cell_type> were found to express a <cell_type>memory phenotype</cell_type> and corresponded to clonal TCRBV3 T-cell expansion ."}
{"id": "2489", "text": "Functionally , p58 ( + ) CTLs displayed a low lytic activity for HLA-A2 tumor and normal cells .", "annotated_text": "Functionally , <cell_type>p58 ( + ) CTLs</cell_type> displayed a low lytic activity for <cell_type>HLA-A2 tumor and normal cells</cell_type> ."}
{"id": "2490", "text": "However , this lytic activity was significantly increased after blockade of p58 with specific monoclonal antibodies .", "annotated_text": "However , this lytic activity was significantly increased after blockade of <protein>p58</protein> with specific <protein>monoclonal antibodies</protein> ."}
{"id": "2491", "text": "Interestingly , we demonstrated that stimulation by tumor cells was required to trigger the inhibitory effect of p58 on the lytic activity of antigen-specific CTLs and that stimulation of the inhibitory function of p58 by tumor cells correlated with an inhibition of nuclear factor-kappaB activation in p58+ tumor-specific CTLS .", "annotated_text": "Interestingly , we demonstrated that stimulation by <cell_type>tumor cells</cell_type> was required to trigger the inhibitory effect of <protein>p58</protein> on the lytic activity of <cell_type>antigen-specific CTLs</cell_type> and that stimulation of the inhibitory function of <protein>p58</protein> by <cell_type>tumor cells</cell_type> correlated with an inhibition of nuclear factor-kappaB activation in <cell_type>p58+ tumor-specific CTLS</cell_type> ."}
{"id": "2492", "text": "T-cell factor-1 expression during human natural killer cell development and in circulating CD56 ( + ) bright natural killer cells .", "annotated_text": "<protein>T-cell factor-1</protein> expression during <cell_type>human natural killer cell</cell_type> development and in circulating <protein>CD56 ( + )</protein> bright <cell_type>natural killer cells</cell_type> ."}
{"id": "2493", "text": "Transcription factors are essential to govern differentiation along the lymphoid lineage from uncommitted hematopoietic stem cells .", "annotated_text": "<protein>Transcription factors</protein> are essential to govern differentiation along the <cell_type>lymphoid lineage</cell_type> from <cell_type>uncommitted hematopoietic stem cells</cell_type> ."}
{"id": "2494", "text": "Although many of these transcription factors have putative roles based on murine knockout experiments , their function in human lymphoid development is less known and was studied further .", "annotated_text": "Although many of these <protein>transcription factors</protein> have putative roles based on murine knockout experiments , their function in human lymphoid development is less known and was studied further ."}
{"id": "2495", "text": "Transcription factor expression in fresh and cultured adult human bone marrow and umbilical cord blood progenitors was evaluated .", "annotated_text": "Transcription factor expression in fresh and cultured <cell_type>adult human bone marrow and umbilical cord blood progenitors</cell_type> was evaluated ."}
{"id": "2496", "text": "We found that fresh CD34 ( + ) Lin ( - ) cells that are human leukocyte antigen ( HLA ) -DR ( - ) or CD38 ( - ) constitutively express GATA-3 but not T-cell factor-1 ( TCF-1 ) or Id-3 .", "annotated_text": "We found that <cell_type>fresh CD34 ( + ) Lin ( - ) cells</cell_type> that are human leukocyte antigen ( HLA ) -DR ( - ) or CD38 ( - ) constitutively express <protein>GATA-3</protein> but not <protein>T-cell factor-1</protein> ( <protein>TCF-1</protein> ) or <protein>Id-3</protein> ."}
{"id": "2497", "text": "Culture with the murine fetal liver cell line AFT024 and defined cytokines was capable of inducing TCF-1 mRNA .", "annotated_text": "Culture with the <cell_line>murine fetal liver cell line AFT024</cell_line> and defined <protein>cytokines</protein> was capable of inducing <rna>TCF-1 mRNA</rna> ."}
{"id": "2498", "text": "However , no T-cell receptor gene rearrangement was identified in cultured progeny .", "annotated_text": "However , no <dna>T-cell receptor gene</dna> rearrangement was identified in cultured progeny ."}
{"id": "2499", "text": "Id-3 , a basic helix loop helix factor with dominant negative function for T-cell differentiation transcription factors , also was upregulated and may explain unsuccessful T-cell maturation .", "annotated_text": "<protein>Id-3</protein> , a <protein>basic helix loop helix factor</protein> with dominant negative function for T-cell differentiation <protein>transcription factors</protein> , also was upregulated and may explain unsuccessful T-cell maturation ."}
{"id": "2500", "text": "To better understand the developmental link between natural killer ( NK ) cells derived from progenitors , we studied NK cell subsets circulating in blood .", "annotated_text": "To better understand the developmental link between <cell_type>natural killer ( NK ) cells</cell_type> derived from <cell_type>progenitors</cell_type> , we studied <cell_type>NK cell subsets</cell_type> circulating in blood ."}
{"id": "2501", "text": "CD56 ( +bright ) , but not CD56 ( +dim ) , NK cells constitutively express TCF-1 by reverse transcriptase polymerase chain reaction and Western blot analysis .", "annotated_text": "<cell_type>CD56 ( +bright )</cell_type> , but not <cell_type>CD56 ( +dim )</cell_type> , <cell_type>NK cells</cell_type> constitutively express <protein>TCF-1</protein> by reverse transcriptase polymerase chain reaction and Western blot analysis ."}
{"id": "2502", "text": "The TCF-1 isoform found in CD56 ( +bright ) cells , which express lectin but not immunoglobulin class I recognizing inhibitory receptors , was identical to that induced in NK cell differentiation culture and was distinctly different from isoforms in T cells .", "annotated_text": "The <protein>TCF-1 isoform</protein> found in <cell_type>CD56 ( +bright ) cells</cell_type> , which express <protein>lectin</protein> but not <protein>immunoglobulin class I</protein> recognizing <protein>inhibitory receptors</protein> , was identical to that induced in NK cell differentiation culture and was distinctly different from isoforms in <cell_type>T cells</cell_type> ."}
{"id": "2503", "text": "These results suggest that TCF-1 does not target human killer immunoglobulin receptor genes , TCF-1 is uniquely expressed in circulating CD56 ( +bright ) NK cells , and specific TCF-1 isoforms may play an important role in regulating NK differentiation from a common NK/T-cell progenitor .", "annotated_text": "These results suggest that <protein>TCF-1</protein> does not target <dna>human killer immunoglobulin receptor genes</dna> , <protein>TCF-1</protein> is uniquely expressed in circulating <cell_type>CD56 ( +bright ) NK cells</cell_type> , and specific <protein>TCF-1 isoforms</protein> may play an important role in regulating NK differentiation from a common <cell_type>NK/T-cell progenitor</cell_type> ."}
{"id": "2504", "text": "Transcriptional activation by a matrix associating region-binding protein .", "annotated_text": "Transcriptional activation by a <protein>matrix associating region-binding protein</protein> ."}
{"id": "2505", "text": "contextual requirements for the function of bright .", "annotated_text": "contextual requirements for the function of <protein>bright</protein> ."}
{"id": "2506", "text": "Bright ( B cell regulator of IgH transcription ) is a B cell -specific , matrix associating region-binding protein that transactivates gene expression from the IgH intronic enhancer ( E mu ) .", "annotated_text": "<protein>Bright</protein> ( <protein>B cell regulator of IgH transcription</protein> ) is a <cell_type>B cell</cell_type> -specific , <protein>matrix associating region-binding protein</protein> that transactivates gene expression from the <dna>IgH intronic enhancer</dna> ( <dna>E mu</dna> ) ."}
{"id": "2507", "text": "We show here that Bright has multiple contextual requirements to function as a transcriptional activator .", "annotated_text": "We show here that <protein>Bright</protein> has multiple contextual requirements to function as a <protein>transcriptional activator</protein> ."}
{"id": "2508", "text": "Bright can not transactivate via out of context , concatenated binding sites .", "annotated_text": "<protein>Bright</protein> can not transactivate via out of context , <protein>concatenated binding sites</protein> ."}
{"id": "2509", "text": "Transactivation is maximal on integrated substrates .", "annotated_text": "Transactivation is maximal on integrated substrates ."}
{"id": "2510", "text": "Two of the three previously identified binding sites in E mu are required for full Bright transactivation .", "annotated_text": "Two of the three previously identified <dna>binding sites</dna> in <dna>E mu</dna> are required for full <protein>Bright</protein> transactivation ."}
{"id": "2511", "text": "The Bright DNA binding domain defined a new family , which includes SWI1 , a component of the SWI.SNF complex shown to have high mobility group-like DNA binding characteristics .", "annotated_text": "The <protein>Bright DNA binding domain</protein> defined a new family , which includes <protein>SWI1</protein> , a component of the <protein>SWI.SNF complex</protein> shown to have high mobility group-like DNA binding characteristics ."}
{"id": "2512", "text": "Similar to one group of high mobility group box proteins , Bright distorts E mu binding site -containing DNA on binding , supporting the concept that it mediates E mu remodeling .", "annotated_text": "Similar to one group of <protein>high mobility group box proteins</protein> , <protein>Bright</protein> distorts <dna>E mu binding site</dna> -containing DNA on binding , supporting the concept that it mediates <dna>E mu</dna> remodeling ."}
{"id": "2513", "text": "Transfection studies further implicate Bright in facilitating spatially separated promoter-enhancer interactions in both transient and stable assays .", "annotated_text": "Transfection studies further implicate <protein>Bright</protein> in facilitating spatially separated promoter-enhancer interactions in both transient and stable assays ."}
{"id": "2514", "text": "Finally , we show that overexpression of Bright leads to enhanced DNase I sensitivity of the endogenous E mu matrix associating regions .", "annotated_text": "Finally , we show that overexpression of <protein>Bright</protein> leads to enhanced DNase I sensitivity of the endogenous <dna>E mu</dna> matrix associating regions ."}
{"id": "2515", "text": "These data further suggest that Bright may contribute to increased gene expression by remodeling the immunoglobulin locus during B cell development .", "annotated_text": "These data further suggest that <protein>Bright</protein> may contribute to increased gene expression by remodeling the <dna>immunoglobulin locus</dna> during <cell_type>B cell</cell_type> development ."}
{"id": "2516", "text": "Analysis of BCL-6 mutations in classic Hodgkin disease of the B- and T-cell type .", "annotated_text": "Analysis of BCL-6 mutations in classic Hodgkin disease of the <cell_type>B- and T-cell type</cell_type> ."}
{"id": "2517", "text": "BCL-6 is essential for germinal center formation and thus for affinity maturation of immunoglobulin ( Ig ) genes by somatic mutations .", "annotated_text": "<dna>BCL-6</dna> is essential for germinal center formation and thus for affinity maturation of <dna>immunoglobulin ( Ig ) genes</dna> by somatic mutations ."}
{"id": "2518", "text": "The 5'-noncoding region of the BCL-6 gene is even a target for the mutation machinery .", "annotated_text": "The <dna>5'-noncoding region</dna> of the <dna>BCL-6 gene</dna> is even a target for the mutation machinery ."}
{"id": "2519", "text": "Translocations of the BCL-6 gene to heterologous promoters and mutations of its 5'-noncoding regulatory region were reported to be potential mechanisms for deregulating BCL-6 expression and for playing a role in the genesis of non-Hodgkin lymphoma .", "annotated_text": "Translocations of the <dna>BCL-6 gene</dna> to <dna>heterologous promoters</dna> and mutations of its <dna>5'-noncoding regulatory region</dna> were reported to be potential mechanisms for deregulating <dna>BCL-6</dna> expression and for playing a role in the genesis of non-Hodgkin lymphoma ."}
{"id": "2520", "text": "In line with this hypothesis is the observation that B-cell lymphoma with somatic mutations , such as diffuse large B-cell lymphoma and follicular lymphoma , also carry BCL-6 mutations , some of which are recurrently detectable .", "annotated_text": "In line with this hypothesis is the observation that B-cell lymphoma with somatic mutations , such as diffuse large B-cell lymphoma and follicular lymphoma , also carry BCL-6 mutations , some of which are recurrently detectable ."}
{"id": "2521", "text": "Classic Hodgkin disease ( cHD ) is also derived from B cells with high loads of somatic mutations and thus a further candidate for BCL-6 mutations .", "annotated_text": "Classic Hodgkin disease ( cHD ) is also derived from <cell_type>B cells</cell_type> with high loads of somatic mutations and thus a further candidate for BCL-6 mutations ."}
{"id": "2522", "text": "To determine the presence and potential role of BCL-6 mutations in cHD , the 5'-noncoding BCL-6 proportion of single Hodgkin and Reed-Sternberg ( HRS ) cells from 6 cases of cHD and 6 cases of HD-derived cell lines was analyzed .", "annotated_text": "To determine the presence and potential role of BCL-6 mutations in cHD , the <dna>5'-noncoding BCL-6</dna> proportion of <cell_type>single Hodgkin and Reed-Sternberg ( HRS ) cells</cell_type> from 6 cases of cHD and 6 cases of <cell_line>HD-derived cell lines</cell_line> was analyzed ."}
{"id": "2523", "text": "All B-cell-derived HD cases and cell lines harbored BCL-6 mutations .", "annotated_text": "All B-cell-derived HD cases and cell lines harbored BCL-6 mutations ."}
{"id": "2524", "text": "In contrast , both T-cell-derived HD cases and cell lines were devoid of BCL-6 mutations .", "annotated_text": "In contrast , both T-cell-derived HD cases and cell lines were devoid of BCL-6 mutations ."}
{"id": "2525", "text": "With only one exception , there were no lymphoma-specific recurrent BCL-6 mutations detected , and BCL-6 protein was absent from the HRS cells of most cases .", "annotated_text": "With only one exception , there were no lymphoma-specific recurrent BCL-6 mutations detected , and <protein>BCL-6 protein</protein> was absent from the <cell_type>HRS cells</cell_type> of most cases ."}
{"id": "2526", "text": "In conclusion , ( 1 ) somatic BCL-6 mutations are restricted to cHD cases of B-cell origin , and ( 2 ) the BCL-6 mutations represent mostly irrelevant somatic base substitutions without consequences for BCL-6 protein expression and the pathogenesis of cHD .", "annotated_text": "In conclusion , ( 1 ) somatic BCL-6 mutations are restricted to cHD cases of <cell_type>B-cell</cell_type> origin , and ( 2 ) the BCL-6 mutations represent mostly irrelevant somatic base substitutions without consequences for <protein>BCL-6 protein</protein> expression and the pathogenesis of cHD ."}
{"id": "2527", "text": "Gadd45gamma is dispensable for normal mouse development and T-cell proliferation .", "annotated_text": "<dna>Gadd45gamma</dna> is dispensable for normal mouse development and T-cell proliferation ."}
{"id": "2528", "text": "Gadd45gamma , a family member of the growth arrest and DNA damage-inducible gene family 45 ( Gadd45 ) , is strongly induced by interleukin-2 ( IL-2 ) in peripheral T cells .", "annotated_text": "<dna>Gadd45gamma</dna> , a family member of the <dna>growth arrest and DNA damage-inducible gene family 45</dna> ( <dna>Gadd45</dna> ) , is strongly induced by <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) in <cell_type>peripheral T cells</cell_type> ."}
{"id": "2529", "text": "While in most tissues all Gadd45 family members are expressed , Gadd45gamma is the only member that is induced by IL-2 .", "annotated_text": "While in most tissues all <dna>Gadd45 family members</dna> are expressed , <dna>Gadd45gamma</dna> is the only member that is induced by <protein>IL-2</protein> ."}
{"id": "2530", "text": "Here we show that the IL-2 -induced expression of Gadd45gamma is dependent on a signaling pathway mediated by the tyrosine kinase Jak3 and the transcription factors Stat5a and Stat5b ( signal transducer and activator of transcription ) .", "annotated_text": "Here we show that the <protein>IL-2</protein> -induced expression of <dna>Gadd45gamma</dna> is dependent on a signaling pathway mediated by the <protein>tyrosine kinase Jak3</protein> and the <protein>transcription factors</protein> <protein>Stat5a</protein> and <protein>Stat5b</protein> ( <protein>signal transducer and activator of transcription</protein> ) ."}
{"id": "2531", "text": "Previous studies with ectopically overexpressed Gadd45gamma in various cell lines implicated its function in negative growth control .", "annotated_text": "Previous studies with ectopically overexpressed <dna>Gadd45gamma</dna> in various cell lines implicated its function in negative growth control ."}
{"id": "2532", "text": "To analyze the physiological role of Gadd45gamma we used homologous recombination to generate mice lacking Gadd45gamma .", "annotated_text": "To analyze the physiological role of <dna>Gadd45gamma</dna> we used homologous recombination to generate mice lacking <dna>Gadd45gamma</dna> ."}
{"id": "2533", "text": "Gadd45gamma -deficient mice develop normally , are indistinguishable from their littermates , and are fertile .", "annotated_text": "<dna>Gadd45gamma</dna> -deficient mice develop normally , are indistinguishable from their littermates , and are fertile ."}
{"id": "2534", "text": "Furthermore , hematopoiesis in mice lacking Gadd45gamma is not impaired and Gadd45gamma -deficient T lymphocytes show normal responses to IL-2 .", "annotated_text": "Furthermore , hematopoiesis in mice lacking <dna>Gadd45gamma</dna> is not impaired and <dna>Gadd45gamma</dna> -deficient <cell_type>T lymphocytes</cell_type> show normal responses to <protein>IL-2</protein> ."}
{"id": "2535", "text": "These data demonstrate that Gadd45gamma is not essential for normal mouse development and hematopoiesis , possibly due to functional redundancy among the Gadd45 family members .", "annotated_text": "These data demonstrate that <dna>Gadd45gamma</dna> is not essential for normal mouse development and hematopoiesis , possibly due to functional redundancy among the <dna>Gadd45 family members</dna> ."}
{"id": "2536", "text": "Gadd45gamma is also dispensable for IL-2 -induced T-cell proliferation .", "annotated_text": "<dna>Gadd45gamma</dna> is also dispensable for <protein>IL-2</protein> -induced T-cell proliferation ."}
{"id": "2537", "text": "Decreased expression of c-myc family genes in thymuses from myasthenia gravis patients .", "annotated_text": "Decreased expression of <dna>c-myc family genes</dna> in thymuses from myasthenia gravis patients ."}
{"id": "2538", "text": "The thymus is a critical organ for the elimination of autoreactive T cells by apoptosis .", "annotated_text": "The thymus is a critical organ for the elimination of <cell_type>autoreactive T cells</cell_type> by apoptosis ."}
{"id": "2539", "text": "We studied the expression of apoptosis-associated genes , bcl-xL , bad , caspase-3 , and c-myc family genes in myasthenia gravis ( MG ) thymuses .", "annotated_text": "We studied the expression of apoptosis-associated genes , <dna>bcl-xL</dna> , <dna>bad</dna> , <dna>caspase-3</dna> , and <dna>c-myc family genes</dna> in myasthenia gravis ( MG ) thymuses ."}
{"id": "2540", "text": "We observed that the mRNA levels of myc family genes , c-myc and max , were markedly reduced in MG thymuses .", "annotated_text": "We observed that the mRNA levels of <dna>myc family genes</dna> , <dna>c-myc</dna> and <dna>max</dna> , were markedly reduced in MG thymuses ."}
{"id": "2541", "text": "These results indicate that c-myc -mediated signaling is abnormal in MG thymuses .", "annotated_text": "These results indicate that <dna>c-myc</dna> -mediated signaling is abnormal in MG thymuses ."}
{"id": "2542", "text": "The levels of molecules whose expressions are associated with myc , such as STAM , prothymosin-alpha , and NFkappaB", "annotated_text": "The levels of molecules whose expressions are associated with <dna>myc</dna> , such as <protein>STAM</protein> , <protein>prothymosin-alpha</protein> , and <protein>NFkappaB</protein>"}
{"id": "2543", "text": "Immunohistochemical detection of interferon-gamma-producing cells in dermatophytosis .", "annotated_text": "Immunohistochemical detection of <cell_type>interferon-gamma-producing cells</cell_type> in dermatophytosis ."}
{"id": "2544", "text": "Skin lesions of dermatophytosis are thought to be a result of a T cell -dependent inflammatory response that is mediated by various cytokines .", "annotated_text": "Skin lesions of dermatophytosis are thought to be a result of a <cell_type>T cell</cell_type> -dependent inflammatory response that is mediated by various <protein>cytokines</protein> ."}
{"id": "2545", "text": "We examined whether IFN-gamma-positive cells ( as expression of Th1 response ) were present in the skin lesions of dermatophytosis in situ by immunohistochemical techniques .", "annotated_text": "We examined whether <cell_type>IFN-gamma-positive cells</cell_type> ( as expression of <cell_type>Th1</cell_type> response ) were present in the skin lesions of dermatophytosis in situ by immunohistochemical techniques ."}
{"id": "2546", "text": "Mixtures of CD4-positive T cells and CD8-positive T cells were found to be present in the dermal infiltrates of the lesions .", "annotated_text": "Mixtures of <cell_type>CD4-positive T cells</cell_type> and <cell_type>CD8-positive T cells</cell_type> were found to be present in the dermal infiltrates of the lesions ."}
{"id": "2547", "text": "Considerable numbers of CD1a-positive cells were detected in the upper dermis and epidermis .", "annotated_text": "Considerable numbers of <cell_type>CD1a-positive cells</cell_type> were detected in the upper dermis and epidermis ."}
{"id": "2548", "text": "A marked accumulation of CD68-positive cells was found in the upper dermis .", "annotated_text": "A marked accumulation of <cell_type>CD68-positive cells</cell_type> was found in the upper dermis ."}
{"id": "2549", "text": "IFN-gamma-positive cells were present in the upper dermis of the lesions .", "annotated_text": "<cell_type>IFN-gamma-positive cells</cell_type> were present in the upper dermis of the lesions ."}
{"id": "2550", "text": "The pattern of IFN-gamma staining appeared to be intracellular in mononuclear lymphoid cells .", "annotated_text": "The pattern of <protein>IFN-gamma</protein> staining appeared to be intracellular in <cell_type>mononuclear lymphoid cells</cell_type> ."}
{"id": "2551", "text": "The staining was considered to be highly specific because it could be completely blocked by preabsorption with recombinant IFN-gamma .", "annotated_text": "The staining was considered to be highly specific because it could be completely blocked by preabsorption with <protein>recombinant IFN-gamma</protein> ."}
{"id": "2552", "text": "Our data support the hypothesis that the skin lesions of dermatophytosis may be associated with a Th1 response .", "annotated_text": "Our data support the hypothesis that the skin lesions of dermatophytosis may be associated with a <cell_type>Th1</cell_type> response ."}
{"id": "2553", "text": "Th1 response , which is characterized by IFN-gamma release , is thought to be involved in the host defense against dermatophytes and to reflect cutaneous reaction in dermatophytosis .", "annotated_text": "<cell_type>Th1</cell_type> response , which is characterized by <protein>IFN-gamma</protein> release , is thought to be involved in the host defense against dermatophytes and to reflect cutaneous reaction in dermatophytosis ."}
{"id": "2554", "text": "Regulation of the helix-loop-helix proteins , E2A and Id3 , by the Ras - ERK MAPK cascade .", "annotated_text": "Regulation of the <protein>helix-loop-helix proteins</protein> , <protein>E2A</protein> and <protein>Id3</protein> , by the <protein>Ras</protein> - <protein>ERK</protein> <protein>MAPK</protein> cascade ."}
{"id": "2555", "text": "Activation of mitogen-activated protein kinase ( MAPK ) pathways leads to cellular differentiation and/or proliferation in a wide variety of cell types , including developing thymocytes .", "annotated_text": "Activation of <protein>mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) pathways leads to cellular differentiation and/or proliferation in a wide variety of cell types , including <cell_type>developing thymocytes</cell_type> ."}
{"id": "2556", "text": "The basic helix-loop-helix ( bHLH ) proteins E12 and E47 and an inhibitor HLH protein , Id3 , play key roles in thymocyte differentiation .", "annotated_text": "The <protein>basic helix-loop-helix ( bHLH ) proteins</protein> <protein>E12</protein> and <protein>E47</protein> and an <protein>inhibitor HLH protein</protein> , <protein>Id3</protein> , play key roles in thymocyte differentiation ."}
{"id": "2557", "text": "We show here that E2A DNA binding is lowered in primary immature thymocytes consequent to T cell receptor ( TCR ) -mediated ligation .", "annotated_text": "We show here that <protein>E2A</protein> DNA binding is lowered in <cell_type>primary immature thymocytes</cell_type> consequent to T cell receptor ( TCR ) -mediated ligation ."}
{"id": "2558", "text": "Whereas expression of E2A mRNA and protein are unaltered , Id3 transcripts are rapidly induced upon signaling from the TCR .", "annotated_text": "Whereas expression of E2A mRNA and protein are unaltered , <rna>Id3 transcripts</rna> are rapidly induced upon signaling from the <protein>TCR</protein> ."}
{"id": "2559", "text": "Activation of Id3 transcription is regulated in a dose-dependent manner by the extracellular signal-regulated kinase ( ERK ) MAPK module .", "annotated_text": "Activation of Id3 transcription is regulated in a dose-dependent manner by the extracellular signal-regulated kinase ( <protein>ERK</protein> ) <protein>MAPK</protein> module ."}
{"id": "2560", "text": "These observations directly connect the ERK MAPK cascade and HLH proteins in a linear pathway .", "annotated_text": "These observations directly connect the <protein>ERK</protein> <protein>MAPK</protein> cascade and <protein>HLH proteins</protein> in a linear pathway ."}
{"id": "2561", "text": "Retinoic acid up-regulates myeloid ICAM-3 expression and function in a cell-specific fashion -- evidence for retinoid signaling pathways in the mast cell lineage .", "annotated_text": "Retinoic acid up-regulates myeloid ICAM-3 expression and function in a cell-specific fashion -- evidence for retinoid signaling pathways in the <cell_type>mast cell lineage</cell_type> ."}
{"id": "2562", "text": "Investigation of mast cell responsiveness toward retinoic acid ( RA ) revealed selective promotion of ICAM-3 expression in the human mast cell line HMC-1 .", "annotated_text": "Investigation of mast cell responsiveness toward retinoic acid ( RA ) revealed selective promotion of <protein>ICAM-3</protein> expression in the <cell_line>human mast cell line HMC-1</cell_line> ."}
{"id": "2563", "text": "This process was dose- and time-dependent and detectable by flow cytometry , Western blot analysis , ELISA , and Northern blot analysis .", "annotated_text": "This process was dose- and time-dependent and detectable by flow cytometry , Western blot analysis , ELISA , and Northern blot analysis ."}
{"id": "2564", "text": "ICAM-3 modulation was found to be cell-type dependent , detectable also for HL-60 cells and monocytes but not U-937 and only weakly for KU812 cells .", "annotated_text": "<protein>ICAM-3</protein> modulation was found to be cell-type dependent , detectable also for <cell_line>HL-60 cells</cell_line> and <cell_type>monocytes</cell_type> but not <cell_line>U-937</cell_line> and only weakly for <cell_line>KU812 cells</cell_line> ."}
{"id": "2565", "text": "Terminally differentiated skin mast cells also failed to up-modulate their ICAM-3 , suggesting the requirement for some degree of immaturity for the process .", "annotated_text": "<cell_type>Terminally differentiated skin mast cells</cell_type> also failed to up-modulate their <protein>ICAM-3</protein> , suggesting the requirement for some degree of immaturity for the process ."}
{"id": "2566", "text": "RA-mediated effects on ICAM-1 expression , studied in parallel , were clearly distinct from those on ICAM-3 .", "annotated_text": "RA-mediated effects on <protein>ICAM-1</protein> expression , studied in parallel , were clearly distinct from those on <protein>ICAM-3</protein> ."}
{"id": "2567", "text": "Investigation of retinoid receptor expression , known to mediate intracellular RA signaling , revealed presence of RAR alpha , RAR gamma , RXR beta , and RXR gamma transcripts in all cell lines studied , and HMC-1 cells were the only line lacking RXR alpha .", "annotated_text": "Investigation of <protein>retinoid receptor</protein> expression , known to mediate intracellular RA signaling , revealed presence of <rna>RAR alpha , RAR gamma , RXR beta , and RXR gamma transcripts</rna> in all cell lines studied , and <cell_line>HMC-1 cells</cell_line> were the only line lacking <protein>RXR alpha</protein> ."}
{"id": "2568", "text": "RAR beta , not expressed at baseline , was induced by RA in a fashion obviously correlating with ICAM-3 up-regulation .", "annotated_text": "<protein>RAR beta</protein> , not expressed at baseline , was induced by RA in a fashion obviously correlating with <protein>ICAM-3</protein> up-regulation ."}
{"id": "2569", "text": "Increased ICAM-3 expression was of functional significance , such that processes stimulated or co-stimulated via ICAM-3 ( homotypic aggregation , IL-8 secretion ) were clearly enhanced upon RA pretreatment , suggesting that RA may contribute via hitherto unrecognized pathways to immune function and host defense .", "annotated_text": "Increased <protein>ICAM-3</protein> expression was of functional significance , such that processes stimulated or co-stimulated via <protein>ICAM-3</protein> ( homotypic aggregation , IL-8 secretion ) were clearly enhanced upon RA pretreatment , suggesting that RA may contribute via hitherto unrecognized pathways to immune function and host defense ."}
{"id": "2570", "text": "CD28 and T cell co-stimulation .", "annotated_text": "<protein>CD28</protein> and <cell_type>T cell</cell_type> co-stimulation ."}
{"id": "2571", "text": "Over the last decade the concept of T cell co-stimulation has emerged to take a central role in the process of T cell activation .", "annotated_text": "Over the last decade the concept of <cell_type>T cell</cell_type> co-stimulation has emerged to take a central role in the process of T cell activation ."}
{"id": "2572", "text": "However , the exact definition of co-stimulation is still unclear .", "annotated_text": "However , the exact definition of co-stimulation is still unclear ."}
{"id": "2573", "text": "In this review , we re-examine the concept of co-stimulation .", "annotated_text": "In this review , we re-examine the concept of co-stimulation ."}
{"id": "2574", "text": "We suggest that while co-stimulation is important , there is little evidence to link co-stimulation with T cell anergy .", "annotated_text": "We suggest that while co-stimulation is important , there is little evidence to link co-stimulation with <cell_type>T cell</cell_type> anergy ."}
{"id": "2575", "text": "We then suggest a framework for studying co-stimulation .", "annotated_text": "We then suggest a framework for studying co-stimulation ."}
{"id": "2576", "text": "Focusing on recent advances in our understanding of CD28 , we discuss four areas of T cell activation where co-stimulation may play a role .", "annotated_text": "Focusing on recent advances in our understanding of <protein>CD28</protein> , we discuss four areas of <cell_type>T cell</cell_type> activation where co-stimulation may play a role ."}
{"id": "2577", "text": "Regulation of activator protein-1 and NF-kappa B in CD8+ T cells exposed to peripheral self-antigens .", "annotated_text": "Regulation of <protein>activator protein-1</protein> and <protein>NF-kappa B</protein> in <cell_type>CD8+ T cells</cell_type> exposed to <protein>peripheral self-antigens</protein> ."}
{"id": "2578", "text": "The transcriptional events that control T cell tolerance to peripheral self Ags are still unknown .", "annotated_text": "The transcriptional events that control <cell_type>T cell</cell_type> tolerance to <protein>peripheral self Ags</protein> are still unknown ."}
{"id": "2579", "text": "In this study , we analyzed the regulation of AP-1 - and NF-kappa B -mediated transcription during in vivo induction of tolerance to a self Ag expressed exclusively on hepatocytes .", "annotated_text": "In this study , we analyzed the regulation of <protein>AP-1</protein> - and <protein>NF-kappa B</protein> -mediated transcription during in vivo induction of tolerance to a <protein>self Ag</protein> expressed exclusively on <cell_type>hepatocytes</cell_type> ."}
{"id": "2580", "text": "Naive CD8 ( + ) Desire ( Des ) ( + ) T cells isolated from the Des TCR-transgenic mice that are specific for the H-2K ( b ) class I Ag were transferred into Alb-K ( b ) -transgenic mice that express the H-2K ( b ) Ag on hepatocytes only .", "annotated_text": "<cell_type>Naive CD8 ( + ) Desire ( Des ) ( + ) T cells</cell_type> isolated from the Des TCR-transgenic mice that are specific for the <protein>H-2K ( b ) class I Ag</protein> were transferred into Alb-K ( b ) -transgenic mice that express the <protein>H-2K ( b ) Ag</protein> on <cell_type>hepatocytes</cell_type> only ."}
{"id": "2581", "text": "Tolerance develops in these mice .", "annotated_text": "Tolerance develops in these mice ."}
{"id": "2582", "text": "We found that the self-reactive CD8 ( + ) Des ( + ) T cells were transiently activated , then became unresponsive and were further deleted .", "annotated_text": "We found that the <cell_type>self-reactive CD8 ( + ) Des ( + ) T cells</cell_type> were transiently activated , then became unresponsive and were further deleted ."}
{"id": "2583", "text": "In contrast to CD8 ( + ) Des ( + ) T cells activated in vivo with APCs , which express high AP-1 and high NF-kappa B transcriptional activity , the unresponsive CD8 ( + ) Des ( + ) T cells expressed no AP-1 and only weak NF-kappa B transcriptional activity .", "annotated_text": "In contrast to <cell_type>CD8 ( + ) Des ( + ) T cells</cell_type> activated in vivo with APCs , which express high <protein>AP-1</protein> and high <protein>NF-kappa B</protein> transcriptional activity , the unresponsive <cell_type>CD8 ( + ) Des ( + ) T cells</cell_type> expressed no <protein>AP-1</protein> and only weak <protein>NF-kappa B</protein> transcriptional activity ."}
{"id": "2584", "text": "The differences in NF-kappa B transcriptional activity correlated with the generation of distinct NF-kappa B complexes .", "annotated_text": "The differences in <protein>NF-kappa B</protein> transcriptional activity correlated with the generation of distinct <protein>NF-kappa B complexes</protein> ."}
{"id": "2585", "text": "Indeed , in vivo primed T cells predominantly express p50/p50 and p65/p50 dimers , whereas these p50-containing complexes are barely detectable in tolerant T cells that express p65- and c-Rel-containing complexes .", "annotated_text": "Indeed , in vivo <cell_type>primed T cells</cell_type> predominantly express <protein>p50/p50 and p65/p50 dimers</protein> , whereas these <protein>p50-containing complexes</protein> are barely detectable in <cell_type>tolerant T cells</cell_type> that express <protein>p65- and c-Rel-containing complexes</protein> ."}
{"id": "2586", "text": "These observations suggest that fine regulation of NF-kappa B complex formation may determine T cell fate .", "annotated_text": "These observations suggest that fine regulation of <protein>NF-kappa B complex</protein> formation may determine <cell_type>T cell</cell_type> fate ."}
{"id": "2587", "text": "Transcriptional regulation in lymphocytes .", "annotated_text": "Transcriptional regulation in <cell_type>lymphocytes</cell_type> ."}
{"id": "2588", "text": "Lymphocytes have been used to investigate many cellular processes , including lineage commitment , differentiation , proliferation and apoptosis .", "annotated_text": "<cell_type>Lymphocytes</cell_type> have been used to investigate many cellular processes , including lineage commitment , differentiation , proliferation and apoptosis ."}
{"id": "2589", "text": "The transcription factors that mediate these processes are often expressed broadly in many cell types .", "annotated_text": "The <protein>transcription factors</protein> that mediate these processes are often expressed broadly in many cell types ."}
{"id": "2590", "text": "The emerging theme is one of cell-type-specific regulation , affecting not only the functional activation of transcription factors but also their access to appropriate regions of DNA .", "annotated_text": "The emerging theme is one of cell-type-specific regulation , affecting not only the functional activation of <protein>transcription factors</protein> but also their access to appropriate regions of DNA ."}
{"id": "2591", "text": "Existence of retinoic acid-receptor -independent retinoid X-receptor -dependent pathway in myeloid cell function .", "annotated_text": "Existence of <protein>retinoic acid-receptor</protein> -independent <protein>retinoid X-receptor</protein> -dependent pathway in <cell_type>myeloid cell</cell_type> function ."}
{"id": "2592", "text": "We previously reported that ER-27191 ( 4- [ 4 , 5 , 7 , 8 , 9 , 10-hexahydro-7 , 7 , 10 , 10-tetramethyl-1- ( 3-pyridylmethyl ) anthra [ 1 , 2-b ] pyrrol-3-yl ] benzoic acid ) is a potent antagonist of retinoic acid receptor ( RAR ) , and ER-35795 ( ( 2E , 4E , 6E ) -7- [ 1- ( 1-methylethyl ) -8-chloro-1 , 2 , 3 , 4-tetrahydroquinolin-6-yl ] -6-fluoro-3-methyl-2 , 4 , 6-nonatrienoic acid ) is a novel retinoid X receptor ( RXR ) -specific agonist .", "annotated_text": "We previously reported that ER-27191 ( 4- [ 4 , 5 , 7 , 8 , 9 , 10-hexahydro-7 , 7 , 10 , 10-tetramethyl-1- ( 3-pyridylmethyl ) anthra [ 1 , 2-b ] pyrrol-3-yl ] benzoic acid ) is a potent antagonist of <protein>retinoic acid receptor</protein> ( <protein>RAR</protein> ) , and ER-35795 ( ( 2E , 4E , 6E ) -7- [ 1- ( 1-methylethyl ) -8-chloro-1 , 2 , 3 , 4-tetrahydroquinolin-6-yl ] -6-fluoro-3-methyl-2 , 4 , 6-nonatrienoic acid ) is a novel <protein>retinoid X receptor</protein> ( <protein>RXR</protein> ) -specific agonist ."}
{"id": "2593", "text": "By using these compounds , we investigated whether distinct RAR -dependent and RXR -dependent pathways operate to mediate the diverse activities of retinoids , particularly , the effects of the RXR pathway on cellular function .", "annotated_text": "By using these compounds , we investigated whether distinct <protein>RAR</protein> -dependent and <protein>RXR</protein> -dependent pathways operate to mediate the diverse activities of retinoids , particularly , the effects of the <protein>RXR</protein> pathway on cellular function ."}
{"id": "2594", "text": "ER-27191 completely antagonized HL60 cell differentiation induced by all-trans-retinoic acid ( atRA ) .", "annotated_text": "ER-27191 completely antagonized <cell_line>HL60 cell</cell_line> differentiation induced by all-trans-retinoic acid ( atRA ) ."}
{"id": "2595", "text": "However , the differentiation induced by the ER-35795 was not antagonized at all by the RAR antagonist , but was inhibited by an RXR homodimer antagonist ( LGD100754 , ( 2E , 4E , 6Z ) -7- ( 3-n-propoxy-5 , 6 , 7 , 8-tetrahydro-5 , 5 , 8 , 8-tetramethylnaphthalen-2-yl ) -3-methylocta-2 , 4 , 6-trienoic acid ) .", "annotated_text": "However , the differentiation induced by the ER-35795 was not antagonized at all by the <protein>RAR</protein> antagonist , but was inhibited by an <protein>RXR homodimer</protein> antagonist ( LGD100754 , ( 2E , 4E , 6Z ) -7- ( 3-n-propoxy-5 , 6 , 7 , 8-tetrahydro-5 , 5 , 8 , 8-tetramethylnaphthalen-2-yl ) -3-methylocta-2 , 4 , 6-trienoic acid ) ."}
{"id": "2596", "text": "Its agonistic action on RXR/RAR heterodimer , on the other hand , was neutralized by the RAR antagonist .", "annotated_text": "Its agonistic action on <protein>RXR/RAR heterodimer</protein> , on the other hand , was neutralized by the <protein>RAR</protein> antagonist ."}
{"id": "2597", "text": "During HL60 cell differentiation , atRA induced RARbeta mRNA , while the RXR had no effect .", "annotated_text": "During <cell_line>HL60 cell</cell_line> differentiation , atRA induced <rna>RARbeta mRNA</rna> , while the <protein>RXR</protein> had no effect ."}
{"id": "2598", "text": "Interestingly , a functional RXR -pathway was also seen in lipopolysaccharide-induced inhibition of mouse splenocyte proliferation .", "annotated_text": "Interestingly , a functional <protein>RXR</protein> -pathway was also seen in lipopolysaccharide-induced inhibition of <cell_type>mouse splenocyte</cell_type> proliferation ."}
{"id": "2599", "text": "These results strongly suggest the existence of a pharmacological RXR -dependent pathway that is activated by a ligand that can bind to RXR .", "annotated_text": "These results strongly suggest the existence of a pharmacological <protein>RXR</protein> -dependent pathway that is activated by a ligand that can bind to <protein>RXR</protein> ."}
{"id": "2600", "text": "Targeting Src homology 2 domain-containing tyrosine phosphatase ( SHP-1 ) into lipid rafts inhibits CD3 -induced T cell activation .", "annotated_text": "Targeting <protein>Src homology 2 domain-containing tyrosine phosphatase</protein> ( <protein>SHP-1</protein> ) into lipid rafts inhibits <protein>CD3</protein> -induced <cell_type>T cell</cell_type> activation ."}
{"id": "2601", "text": "To study the mechanism by which protein tyrosine phosphatases ( PTPs ) regulate CD3 -induced tyrosine phosphorylation , we investigated the distribution of PTPs in subdomains of plasma membrane .", "annotated_text": "To study the mechanism by which <protein>protein tyrosine phosphatases</protein> ( <protein>PTPs</protein> ) regulate <protein>CD3</protein> -induced tyrosine phosphorylation , we investigated the distribution of <protein>PTPs</protein> in subdomains of plasma membrane ."}
{"id": "2602", "text": "We report here that the bulk PTP activity associated with T cell membrane is present outside the lipid rafts , as determined by sucrose density gradient sedimentation .", "annotated_text": "We report here that the bulk <protein>PTP</protein> activity associated with <cell_type>T cell</cell_type> membrane is present outside the lipid rafts , as determined by sucrose density gradient sedimentation ."}
{"id": "2603", "text": "In Jurkat T cells , approximately 5 -- 10 % of Src homology 2 domain-containing tyrosine phosphatase ( SHP-1 ) is constitutively associated with plasma membrane , and nearly 50 % of SHP-2 is translocated to plasma membrane after vanadate treatment .", "annotated_text": "In <cell_line>Jurkat T cells</cell_line> , approximately 5 -- 10 % of <protein>Src homology 2 domain-containing tyrosine phosphatase</protein> ( <protein>SHP-1</protein> ) is constitutively associated with plasma membrane , and nearly 50 % of <protein>SHP-2</protein> is translocated to plasma membrane after vanadate treatment ."}
{"id": "2604", "text": "Similar to transmembrane PTP , CD45 , the membrane-associated populations of SHP-1 and SHP-2 are essentially excluded from lipid rafts , where other signaling molecules such as Lck , linker for activation of T cells , and CD3 zeta are enriched .", "annotated_text": "Similar to <protein>transmembrane PTP</protein> , <protein>CD45</protein> , the membrane-associated populations of <protein>SHP-1</protein> and <protein>SHP-2</protein> are essentially excluded from lipid rafts , where other <protein>signaling molecules</protein> such as <protein>Lck , linker for activation of T cells</protein> , and <protein>CD3 zeta</protein> are enriched ."}
{"id": "2605", "text": "We further demonstrated that CD3 -induced tyrosine phosphorylation of these substrates is largely restricted to lipid rafts , unless PTPs are inhibited .", "annotated_text": "We further demonstrated that <protein>CD3</protein> -induced tyrosine phosphorylation of these substrates is largely restricted to lipid rafts , unless <protein>PTPs</protein> are inhibited ."}
{"id": "2606", "text": "It suggests that a restricted partition of PTPs among membrane subdomains may regulate protein tyrosine phosphorylation in T cell membrane .", "annotated_text": "It suggests that a restricted partition of <protein>PTPs</protein> among membrane subdomains may regulate protein tyrosine phosphorylation in <cell_type>T cell</cell_type> membrane ."}
{"id": "2607", "text": "To test this hypothesis , we targeted SHP-1 into lipid rafts by using the N-terminal region of Lck ( residues 1 -- 14 ) .", "annotated_text": "To test this hypothesis , we targeted <protein>SHP-1</protein> into lipid rafts by using the <protein>N-terminal region of Lck</protein> ( <protein>residues 1 -- 14</protein> ) ."}
{"id": "2608", "text": "The results indicate that the expression of Lck/SHP-1 chimera inside lipid rafts profoundly inhibits CD3 -induced tyrosine phosphorylation of CD3 zeta/epsilon , IL-2 generation , and nuclear mobilization of NF-AT .", "annotated_text": "The results indicate that the expression of <protein>Lck/SHP-1 chimera</protein> inside lipid rafts profoundly inhibits <protein>CD3</protein> -induced tyrosine phosphorylation of <protein>CD3 zeta/epsilon</protein> , IL-2 generation , and nuclear mobilization of <protein>NF-AT</protein> ."}
{"id": "2609", "text": "Collectively , these results suggest that the exclusion of PTPs from lipid rafts may be a mechanism that potentiates TCR / CD3 activation", "annotated_text": "Collectively , these results suggest that the exclusion of <protein>PTPs</protein> from lipid rafts may be a mechanism that potentiates <protein>TCR</protein> / <protein>CD3</protein> activation"}
{"id": "2610", "text": "An instructive component in T helper cell type 2 ( Th2 ) development mediated by GATA-3 .", "annotated_text": "An instructive component in <cell_type>T helper cell type 2</cell_type> ( <cell_type>Th2</cell_type> ) development mediated by <protein>GATA-3</protein> ."}
{"id": "2611", "text": "Although interleukin ( IL ) -12 and IL-4 polarize naive CD4 ( + ) T cells toward T helper cell type 1 ( Th1 ) or Th2 phenotypes , it is not known whether cytokines instruct the developmental fate in uncommitted progenitors or select for outgrowth of cells that have stochastically committed to a particular fate .", "annotated_text": "Although <protein>interleukin ( IL ) -12</protein> and <protein>IL-4</protein> polarize <cell_type>naive CD4 ( + ) T cells</cell_type> toward T helper cell type 1 ( Th1 ) or Th2 phenotypes , it is not known whether <protein>cytokines</protein> instruct the developmental fate in <cell_type>uncommitted progenitors</cell_type> or select for outgrowth of cells that have stochastically committed to a particular fate ."}
{"id": "2612", "text": "To distinguish these instructive and selective models , we used surface affinity matrix technology to isolate committed progenitors based on cytokine secretion phenotype and developed retroviral-based tagging approaches to directly monitor individual progenitor fate decisions at the clonal and population levels .", "annotated_text": "To distinguish these instructive and selective models , we used surface affinity matrix technology to isolate <cell_type>committed progenitors</cell_type> based on cytokine secretion phenotype and developed retroviral-based tagging approaches to directly monitor individual progenitor fate decisions at the clonal and population levels ."}
{"id": "2613", "text": "We observe IL-4 -dependent redirection of phenotype in cells that have already committed to a non-IL-4-producing fate , inconsistent with predictions of the selective model .", "annotated_text": "We observe <protein>IL-4</protein> -dependent redirection of phenotype in cells that have already committed to a non-IL-4-producing fate , inconsistent with predictions of the selective model ."}
{"id": "2614", "text": "Further , retroviral tagging of naive progenitors with the Th2-specific transcription factor GATA-3 provided direct evidence for instructive differentiation , and no evidence for the selective outgrowth of cells committed to either the Th1 or Th2 fate .", "annotated_text": "Further , retroviral tagging of <cell_type>naive progenitors</cell_type> with the <protein>Th2-specific transcription factor GATA-3</protein> provided direct evidence for instructive differentiation , and no evidence for the selective outgrowth of cells committed to either the Th1 or Th2 fate ."}
{"id": "2615", "text": "These data would seem to exclude selection as an exclusive mechanism in Th1 / Th2 differentiation , and support an instructive model of cytokine-driven transcriptional programming of cell fate decisions .", "annotated_text": "These data would seem to exclude selection as an exclusive mechanism in <cell_type>Th1</cell_type> / <cell_type>Th2</cell_type> differentiation , and support an instructive model of cytokine-driven transcriptional programming of cell fate decisions ."}
{"id": "2616", "text": "In vitro-activated human lupus T cells express normal estrogen receptor proteins which bind to the estrogen response element .", "annotated_text": "In vitro-activated <cell_type>human lupus T cells</cell_type> express normal <protein>estrogen receptor proteins</protein> which bind to the <protein>estrogen response element</protein> ."}
{"id": "2617", "text": "We have shown that estrogen receptor ( ERalpha , ERbeta ) transcripts are expressed in SLE and normal T cells .", "annotated_text": "We have shown that <protein>estrogen receptor</protein> ( <protein>ERalpha</protein> , <protein>ERbeta</protein> ) transcripts are expressed in <cell_type>SLE and normal T cells</cell_type> ."}
{"id": "2618", "text": "In this study , T cell nuclear extracts from female lupus patients and normal donors were tested for biologically active ER proteins capable of binding to the human estrogen response element ( hERE ) by electrophoretic mobility shift assays .", "annotated_text": "In this study , T cell nuclear extracts from female lupus patients and normal donors were tested for biologically active <protein>ER proteins</protein> capable of binding to the <dna>human estrogen response element</dna> ( <dna>hERE</dna> ) by electrophoretic mobility shift assays ."}
{"id": "2619", "text": "When peripheral blood T cells were stimulated with 17beta-estradiol ( E2 ) , PMA and ionomycin , two major retarded bands in T cell nuclear extracts exhibited a migration pattern similar to slow migrating protein-ERE complexes in human breast cancer cell extracts .", "annotated_text": "When <cell_type>peripheral blood T cells</cell_type> were stimulated with 17beta-estradiol ( E2 ) , PMA and ionomycin , two major retarded bands in T cell nuclear extracts exhibited a migration pattern similar to slow migrating <protein>protein-ERE complexes</protein> in human breast cancer cell extracts ."}
{"id": "2620", "text": "T cells cultured only with E2 did not have these complexes .", "annotated_text": "<cell_type>T cells</cell_type> cultured only with E2 did not have these complexes ."}
{"id": "2621", "text": "The formation of the complexes was inhibited by competition with the hERE cold oligonucleotide and partially with anti-ERalpha antibodies .", "annotated_text": "The formation of the complexes was inhibited by competition with the hERE cold oligonucleotide and partially with <protein>anti-ERalpha antibodies</protein> ."}
{"id": "2622", "text": "There was no notable difference in the migration pattern of ERE-binding proteins between the SLE and normal T cell extracts .", "annotated_text": "There was no notable difference in the migration pattern of <protein>ERE-binding proteins</protein> between the SLE and normal T cell extracts ."}
{"id": "2623", "text": "Together , these results suggest that activated human T cells , whether lupus-derived or normal-derived , contain biologically active ERalpha proteins .", "annotated_text": "Together , these results suggest that <cell_type>activated human T cells</cell_type> , whether lupus-derived or normal-derived , contain biologically active <protein>ERalpha proteins</protein> ."}
{"id": "2624", "text": "Other factors may be responsible for differential sensitivity of lupus T cells to estrogen .", "annotated_text": "Other factors may be responsible for differential sensitivity of <cell_type>lupus T cells</cell_type> to estrogen ."}
{"id": "2625", "text": "Mechanism of the inhibitory effect of protease inhibitor on tumor necrosis factor alpha production of monocytes .", "annotated_text": "Mechanism of the inhibitory effect of protease inhibitor on <protein>tumor necrosis factor alpha</protein> production of <cell_type>monocytes</cell_type> ."}
{"id": "2626", "text": "If the inflammatory response becomes excessive or uncontrolled by some stimuli , inappropriate inflammatory responses occur .", "annotated_text": "If the inflammatory response becomes excessive or uncontrolled by some stimuli , inappropriate inflammatory responses occur ."}
{"id": "2627", "text": "Monocytes are extremely important cells for regulating the cytokine network and tumor necrosis factor alpha ( TNFalpha ) and interleukin- ( IL ) 10 , which are mainly synthesized by monocytes , are representative cytokines that play a central role in the cytokine network .", "annotated_text": "<cell_type>Monocytes</cell_type> are extremely important cells for regulating the cytokine network and <protein>tumor necrosis factor alpha</protein> ( <protein>TNFalpha</protein> ) and <protein>interleukin- ( IL ) 10</protein> , which are mainly synthesized by <cell_type>monocytes</cell_type> , are representative <protein>cytokines</protein> that play a central role in the cytokine network ."}
{"id": "2628", "text": "Protease inhibitors such as gabexate mesilate ( GM ) and ulinastatin ( UTI ) have been shown to have various beneficial effects by inhibiting the activation of leukocytes , but the mechanism for this has yet to be fully elucidated .", "annotated_text": "Protease inhibitors such as gabexate mesilate ( GM ) and ulinastatin ( UTI ) have been shown to have various beneficial effects by inhibiting the activation of <cell_type>leukocytes</cell_type> , but the mechanism for this has yet to be fully elucidated ."}
{"id": "2629", "text": "In this study we investigated the mechanism of the inhibitory effect of protease inhibitors on the proinflammatory cytokine production of lipopolysaccharide- ( LPS ) stimulated monocytes .", "annotated_text": "In this study we investigated the mechanism of the inhibitory effect of protease inhibitors on the proinflammatory cytokine production of lipopolysaccharide- ( LPS ) stimulated <cell_type>monocytes</cell_type> ."}
{"id": "2630", "text": "LPS-stimulated monocytes were treated with GM or UTI .", "annotated_text": "LPS-stimulated <cell_type>monocytes</cell_type> were treated with GM or UTI ."}
{"id": "2631", "text": "The value of TNFalpha and IL-10 in the culture medium of monocytes was measured and each mRNA expression was assayed .", "annotated_text": "The value of <protein>TNFalpha</protein> and <protein>IL-10</protein> in the culture medium of <cell_type>monocytes</cell_type> was measured and each mRNA expression was assayed ."}
{"id": "2632", "text": "The inhibitory effect of protease inhibitors on the activity of intracellular signal transduction pathways such as protein kinase C ( PKC ) and nuclear factor kappa B ( NFkappaB ) were also evaluated .", "annotated_text": "The inhibitory effect of protease inhibitors on the activity of intracellular signal transduction pathways such as <protein>protein kinase C</protein> ( <protein>PKC</protein> ) and <protein>nuclear factor kappa B</protein> ( <protein>NFkappaB</protein> ) were also evaluated ."}
{"id": "2633", "text": "GM decreased the TNFalpha production of LPS-stimulated monocytes as shown by the inhibition of mRNA expression and increased the IL-10 production of LPS-stimulated monocytes .", "annotated_text": "GM decreased the <protein>TNFalpha</protein> production of LPS-stimulated <cell_type>monocytes</cell_type> as shown by the inhibition of mRNA expression and increased the <protein>IL-10</protein> production of LPS-stimulated <cell_type>monocytes</cell_type> ."}
{"id": "2634", "text": "GM also suppressed the NFkappaB activity of LPS-stimulated monocytes .", "annotated_text": "GM also suppressed the <protein>NFkappaB</protein> activity of LPS-stimulated <cell_type>monocytes</cell_type> ."}
{"id": "2635", "text": "UTI decreased the TNFalpha production of LPS-stimulated monocytes , but did not inhibit the TNFalpha mRNA expression .", "annotated_text": "UTI decreased the <protein>TNFalpha</protein> production of LPS-stimulated <cell_type>monocytes</cell_type> , but did not inhibit the <rna>TNFalpha mRNA</rna> expression ."}
{"id": "2636", "text": "The present study shows that the inhibitory effect of GM on the TNFalpha production of activated human monocytes is mediated by the suppression of NFkappaB activation , while the mechanism of UTI inhibiting TNFalpha production of human monocytes may be due to the inhibition of either the translation or secretion of TNFalpha .", "annotated_text": "The present study shows that the inhibitory effect of GM on the <protein>TNFalpha</protein> production of activated <cell_type>human monocytes</cell_type> is mediated by the suppression of <protein>NFkappaB</protein> activation , while the mechanism of UTI inhibiting <protein>TNFalpha</protein> production of <cell_type>human monocytes</cell_type> may be due to the inhibition of either the translation or secretion of <protein>TNFalpha</protein> ."}
{"id": "2637", "text": "Homocysteine stimulates the expression of monocyte chemoattractant protein-1 in endothelial cells leading to enhanced monocyte chemotaxis .", "annotated_text": "Homocysteine stimulates the expression of <protein>monocyte chemoattractant protein-1</protein> in <cell_type>endothelial cells</cell_type> leading to enhanced monocyte chemotaxis ."}
{"id": "2638", "text": "Hyperhomocysteinemia has been identified as an independent risk factor for atherosclerosis .", "annotated_text": "Hyperhomocysteinemia has been identified as an independent risk factor for atherosclerosis ."}
{"id": "2639", "text": "The infiltration of monocytes into the arterial wall is one of the key events during atherogenesis .", "annotated_text": "The infiltration of <cell_type>monocytes</cell_type> into the arterial wall is one of the key events during atherogenesis ."}
{"id": "2640", "text": "Monocyte chemoattractant protein-1 ( MCP-1 ) is a potent chemokine that stimulates the migration of monocytes into the intima of the arterial wall .", "annotated_text": "<protein>Monocyte chemoattractant protein-1</protein> ( <protein>MCP-1</protein> ) is a potent <protein>chemokine</protein> that stimulates the migration of <cell_type>monocytes</cell_type> into the intima of the arterial wall ."}
{"id": "2641", "text": "The mechanism by which increased monocyte infiltration occurs in atherosclerotic lesions in patients with hyperhomocysteinemia has not been delineated .", "annotated_text": "The mechanism by which increased monocyte infiltration occurs in atherosclerotic lesions in patients with hyperhomocysteinemia has not been delineated ."}
{"id": "2642", "text": "The objective of the present study was to investigate the effect of homocysteine on MCP-1 production in endothelial cells .", "annotated_text": "The objective of the present study was to investigate the effect of homocysteine on <protein>MCP-1</protein> production in <cell_type>endothelial cells</cell_type> ."}
{"id": "2643", "text": "Cells were incubated with homocysteine .", "annotated_text": "Cells were incubated with homocysteine ."}
{"id": "2644", "text": "The secretion of MCP-1 protein was significantly increased ( 195 % as compared to the control ) in cells treated with pathological concentrations of homocysteine .", "annotated_text": "The secretion of <protein>MCP-1 protein</protein> was significantly increased ( 195 % as compared to the control ) in cells treated with pathological concentrations of homocysteine ."}
{"id": "2645", "text": "Such effect was accompanied by an increased expression of MCP-1 mRNA ( 176 % as compared to the control ) in endothelial cells which resulted in enhanced monocyte chemotaxis .", "annotated_text": "Such effect was accompanied by an increased expression of <rna>MCP-1 mRNA</rna> ( 176 % as compared to the control ) in <cell_type>endothelial cells</cell_type> which resulted in enhanced monocyte chemotaxis ."}
{"id": "2646", "text": "The p38 MAP kinase as well as other members of the p38 MAP kinase pathway , including MKK3 , MKK6 , ATF-2 and Elk-1 , were activated in homocysteine-treated cells .", "annotated_text": "The <protein>p38 MAP kinase</protein> as well as other members of the p38 MAP kinase pathway , including <protein>MKK3</protein> , <protein>MKK6</protein> , <protein>ATF-2</protein> and <protein>Elk-1</protein> , were activated in <cell_type>homocysteine-treated cells</cell_type> ."}
{"id": "2647", "text": "Homocysteine-induced MCP-1 expression and subsequent monocyte chemotaxis were blocked by a p38 MAP kinase inhibitor ( SB203580 ) suggesting that the p38 MAP kinase pathway might be involved in homocysteine-induced MCP-1 expression in endothelial cells .", "annotated_text": "Homocysteine-induced <protein>MCP-1</protein> expression and subsequent monocyte chemotaxis were blocked by a <protein>p38 MAP kinase</protein> inhibitor ( SB203580 ) suggesting that the <protein>p38 MAP kinase</protein> pathway might be involved in homocysteine-induced <protein>MCP-1</protein> expression in <cell_type>endothelial cells</cell_type> ."}
{"id": "2648", "text": "In contrast , staurosporine , a protein kinase C inhibitor , had no effect on homocysteine-induced MCP-1 expression .", "annotated_text": "In contrast , staurosporine , a <protein>protein kinase C</protein> inhibitor , had no effect on homocysteine-induced <protein>MCP-1</protein> expression ."}
{"id": "2649", "text": "In conclusion , our results indicate that homocysteine stimulates MCP-1 expression in endothelial cells leading to enhanced monocyte chemotaxis .", "annotated_text": "In conclusion , our results indicate that homocysteine stimulates <protein>MCP-1</protein> expression in <cell_type>endothelial cells</cell_type> leading to enhanced monocyte chemotaxis ."}
{"id": "2650", "text": "Inducible resistance to Fas-mediated apoptosis in B cells .", "annotated_text": "Inducible resistance to Fas-mediated apoptosis in <cell_type>B cells</cell_type> ."}
{"id": "2651", "text": "Apoptosis produced in B cells through Fas ( APO-1 , CD95 ) triggering is regulated by signals derived from other surface receptors : CD40 engagement produces upregulation of Fas expression and marked susceptibility to Fas -induced cell death , whereas antigen receptor engagement , or IL-4R engagement , inhibits Fas killing and in so doing induces a state of Fas -resistance , even in otherwise sensitive , CD40 -stimulated targets .", "annotated_text": "Apoptosis produced in <cell_type>B cells</cell_type> through <protein>Fas</protein> ( <protein>APO-1</protein> , <protein>CD95</protein> ) triggering is regulated by signals derived from other surface receptors : CD40 engagement produces upregulation of <protein>Fas</protein> expression and marked susceptibility to <protein>Fas</protein> -induced cell death , whereas antigen receptor engagement , or IL-4R engagement , inhibits <protein>Fas</protein> killing and in so doing induces a state of <protein>Fas</protein> -resistance , even in otherwise sensitive , <protein>CD40</protein> -stimulated targets ."}
{"id": "2652", "text": "Surface immunoglobulin and IL-4R utilize at least partially distinct pathways to produce Fas -resistance that differentially depend on PKC and STAT6 , respectively .", "annotated_text": "<protein>Surface immunoglobulin</protein> and <protein>IL-4R</protein> utilize at least partially distinct pathways to produce <protein>Fas</protein> -resistance that differentially depend on <protein>PKC</protein> and <protein>STAT6</protein> , respectively ."}
{"id": "2653", "text": "Further , surface immunoglobulin signaling for inducible Fas -resistance bypasses Btk , requires NF-kappaB , and entails new macromolecular synthesis .", "annotated_text": "Further , surface immunoglobulin signaling for inducible <protein>Fas</protein> -resistance bypasses <protein>Btk</protein> , requires <protein>NF-kappaB</protein> , and entails new macromolecular synthesis ."}
{"id": "2654", "text": "Terminal effectors of B cell Fas -resistance include the known anti-apoptotic gene products , Bcl-xL and FLIP , and a novel anti-apoptotic gene that encodes FAIM ( Fas Apoptosis Inhibitory Molecule ) .", "annotated_text": "Terminal effectors of <cell_type>B cell</cell_type> <protein>Fas</protein> -resistance include the known <protein>anti-apoptotic gene products</protein> , <protein>Bcl-xL</protein> and <protein>FLIP</protein> , and a novel <dna>anti-apoptotic gene</dna> that encodes <protein>FAIM</protein> ( <protein>Fas Apoptosis Inhibitory Molecule</protein> ) ."}
{"id": "2655", "text": "faim was identified by differential display and exists in two alternatively spliced forms ; faim-S is broadly expressed , but faim-L expression is tissue-specific .", "annotated_text": "<protein>faim</protein> was identified by differential display and exists in two alternatively spliced forms ; <protein>faim-S</protein> is broadly expressed , but faim-L expression is tissue-specific ."}
{"id": "2656", "text": "The FAIM sequence is highly evolu- tionarily conserved , suggesting an important role for this molecule throughout phylogeny .", "annotated_text": "The <dna>FAIM sequence</dna> is highly evolu- tionarily conserved , suggesting an important role for this molecule throughout phylogeny ."}
{"id": "2657", "text": "Inducible resistance to Fas killing is hypothesized to protect foreign antigen-specific B cells during potentially hazardous interactions with FasL-bearing T cells , whereas autoreactive B cells fail to become Fas -resistant and are deleted via Fas -dependent cytotoxicity .", "annotated_text": "Inducible resistance to <protein>Fas</protein> killing is hypothesized to protect foreign antigen-specific <cell_type>B cells</cell_type> during potentially hazardous interactions with <cell_type>FasL-bearing T cells</cell_type> , whereas <cell_type>autoreactive B cells</cell_type> fail to become <protein>Fas</protein> -resistant and are deleted via <protein>Fas</protein> -dependent cytotoxicity ."}
{"id": "2658", "text": "Inadvertent or aberrant acquisition of Fas -resistance may permit autoreactive B cells to escape Fas deletion , and malignant lymphocytes to impede anti-tumor immunity .", "annotated_text": "Inadvertent or aberrant acquisition of <protein>Fas</protein> -resistance may permit <cell_type>autoreactive B cells</cell_type> to escape <protein>Fas</protein> deletion , and <cell_type>malignant lymphocytes</cell_type> to impede anti-tumor immunity ."}
{"id": "2659", "text": "Stromal cell-derived factor 1 alpha -induced chemotaxis in T cells is mediated by nitric oxide signaling pathways .", "annotated_text": "<protein>Stromal cell-derived factor 1 alpha</protein> -induced chemotaxis in <cell_type>T cells</cell_type> is mediated by nitric oxide signaling pathways ."}
{"id": "2660", "text": "Stromal cell-derived factor 1 alpha ( SDF1 alpha ) and its cognate chemokine receptor CXCR4 act as potent chemoattractants and regulate trafficking and homing of hematopoietic progenitor cells and lymphocytes .", "annotated_text": "<protein>Stromal cell-derived factor 1 alpha</protein> ( <protein>SDF1 alpha</protein> ) and its cognate <protein>chemokine receptor CXCR4</protein> act as potent chemoattractants and regulate trafficking and homing of <cell_type>hematopoietic progenitor cells</cell_type> and <cell_type>lymphocytes</cell_type> ."}
{"id": "2661", "text": "However , the molecular mechanisms regulating SDF1 alpha -driven cell migration are not well defined .", "annotated_text": "However , the molecular mechanisms regulating <protein>SDF1 alpha</protein> -driven cell migration are not well defined ."}
{"id": "2662", "text": "In this study , we have explored the roles of the second messenger NO and the transcription factor NF-kappa B in SDF1 alpha -induced T cell migration .", "annotated_text": "In this study , we have explored the roles of the second messenger NO and the <protein>transcription factor NF-kappa B</protein> in <protein>SDF1 alpha</protein> -induced T cell migration ."}
{"id": "2663", "text": "SDF1 alpha treatment of Jurkat T cells increased the activity of NO synthase , which catalyzes the generation of NO .", "annotated_text": "<protein>SDF1 alpha</protein> treatment of <cell_line>Jurkat T cells</cell_line> increased the activity of <protein>NO synthase</protein> , which catalyzes the generation of NO ."}
{"id": "2664", "text": "We observed that pretreatment of Jurkat cells or activated PBLs with several NO donors significantly enhanced the SDF1 alpha -induced migration , whereas various inhibitors of NO synthase markedly abrogated the chemotactic response in a concentration-dependent manner .", "annotated_text": "We observed that pretreatment of <cell_line>Jurkat cells</cell_line> or activated <cell_type>PBLs</cell_type> with several NO donors significantly enhanced the <protein>SDF1 alpha</protein> -induced migration , whereas various inhibitors of <protein>NO synthase</protein> markedly abrogated the chemotactic response in a concentration-dependent manner ."}
{"id": "2665", "text": "Furthermore , we observed that inhibitors of the transcription factor NF-kappa B , which is linked to NO signaling pathways , also significantly blocked the SDF1 alpha -induced chemotactic response .", "annotated_text": "Furthermore , we observed that inhibitors of the <protein>transcription factor NF-kappa B</protein> , which is linked to NO signaling pathways , also significantly blocked the <protein>SDF1 alpha</protein> -induced chemotactic response ."}
{"id": "2666", "text": "However , these compounds did not have a significant effect on SDF1 alpha -induced mitogen-activated protein kinase activity .", "annotated_text": "However , these compounds did not have a significant effect on <protein>SDF1 alpha</protein> -induced mitogen-activated protein kinase activity ."}
{"id": "2667", "text": "In addition , the MAP/Erk kinase kinase inhibitor PD98059 did not abrogate SDF1 alpha -induced chemotaxis .", "annotated_text": "In addition , the MAP/Erk kinase kinase inhibitor PD98059 did not abrogate <protein>SDF1 alpha</protein> -induced chemotaxis ."}
{"id": "2668", "text": "AKT , which has been shown to mediate NO production , was also phosphorylated upon SDF1 alpha stimulation .", "annotated_text": "<protein>AKT</protein> , which has been shown to mediate NO production , was also phosphorylated upon <protein>SDF1 alpha</protein> stimulation ."}
{"id": "2669", "text": "These studies suggest that NO-related signaling pathways may mediate SDF1 alpha -induced chemotaxis , but not mitogen-activated protein kinase activation .", "annotated_text": "These studies suggest that NO-related signaling pathways may mediate <protein>SDF1 alpha</protein> -induced chemotaxis , but not <protein>mitogen-activated protein kinase</protein> activation ."}
{"id": "2670", "text": "The lack of NF-kappa B transactivation and PKC epsilon expression in CD4 ( + ) CD8 ( + ) thymocytes correlates with negative selection .", "annotated_text": "The lack of NF-kappa B transactivation and PKC epsilon expression in <cell_type>CD4 ( + ) CD8 ( + ) thymocytes</cell_type> correlates with negative selection ."}
{"id": "2671", "text": "Deletion of autoreactive thymocytes at the DP stage is the basis for tolerance to thymus-expressed self antigens .", "annotated_text": "Deletion of <cell_type>autoreactive thymocytes</cell_type> at the DP stage is the basis for tolerance to <protein>thymus-expressed self antigens</protein> ."}
{"id": "2672", "text": "In this study we investigated whether distinct signalling pathways are induced in DP thymocytes as compared to mature T cells upon stimulation with antigen .", "annotated_text": "In this study we investigated whether distinct signalling pathways are induced in <cell_type>DP thymocytes</cell_type> as compared to <cell_type>mature T cells</cell_type> upon stimulation with antigen ."}
{"id": "2673", "text": "Using triple transgenic mice expressing a TCR transgene , dominant negative ras/Mek proteins and a reporter gene construct with AP-1 or NF-kappa B binding sites , we showed a complete lack of transcriptional activity of NF-kappa B but not AP-1 in DP thymocytes , whereas both were transcriptionally active in mature T cells after antigenic stimulation .", "annotated_text": "Using triple transgenic mice expressing a <dna>TCR transgene</dna> , <protein>dominant negative ras/Mek proteins</protein> and a <dna>reporter gene construct</dna> with <dna>AP-1 or NF-kappa B binding sites</dna> , we showed a complete lack of transcriptional activity of <protein>NF-kappa B</protein> but not <protein>AP-1</protein> in <cell_type>DP thymocytes</cell_type> , whereas both were transcriptionally active in <cell_type>mature T cells</cell_type> after antigenic stimulation ."}
{"id": "2674", "text": "Lack of NF-kappa B induction correlated with increased death in response to antigen .", "annotated_text": "Lack of <protein>NF-kappa B</protein> induction correlated with increased death in response to <protein>antigen</protein> ."}
{"id": "2675", "text": "AP-1 induction was dependent on the integrity of the ras/Mek pathway indicating that this pathway was activated in the DP thymocytes .", "annotated_text": "<protein>AP-1</protein> induction was dependent on the integrity of the ras/Mek pathway indicating that this pathway was activated in the <cell_type>DP thymocytes</cell_type> ."}
{"id": "2676", "text": "In contrast , we found a complete lack of constitutive expression of the epsilon isoform of Protein Kinase C ( PKC ) in DP thymocytes , although it was present in mature thymocytes and peripheral T cells .", "annotated_text": "In contrast , we found a complete lack of constitutive expression of the <protein>epsilon isoform of Protein Kinase C</protein> ( <protein>PKC</protein> ) in <cell_type>DP thymocytes</cell_type> , although it was present in <cell_type>mature thymocytes</cell_type> and <cell_type>peripheral T cells</cell_type> ."}
{"id": "2677", "text": "Taken together the results suggest that the lack of PKC epsilon in DP thymocytes could lead to the absence of NF-kappa B activity after antigenic stimulation contributing to negative selection .", "annotated_text": "Taken together the results suggest that the lack of <protein>PKC epsilon</protein> in <cell_type>DP thymocytes</cell_type> could lead to the absence of <protein>NF-kappa B</protein> activity after antigenic stimulation contributing to negative selection ."}
{"id": "2678", "text": "Cell Death and Differentiation ( 2000 ) 7 , 1253 - 1262 .", "annotated_text": "Cell Death and Differentiation ( 2000 ) 7 , 1253 - 1262 ."}
{"id": "2679", "text": "CD2 stimulation leads to the delayed and prolonged activation of STAT1 in T cells but not NK cells .", "annotated_text": "CD2 stimulation leads to the delayed and prolonged activation of <protein>STAT1</protein> in <cell_type>T cells</cell_type> but not <cell_type>NK cells</cell_type> ."}
{"id": "2680", "text": "OBJECTIVE : T lymphocytes can be activated by soluble factors such as cytokines or through direct cell-cell interactions .", "annotated_text": "OBJECTIVE : <cell_type>T lymphocytes</cell_type> can be activated by soluble factors such as <protein>cytokines</protein> or through direct cell-cell interactions ."}
{"id": "2681", "text": "Although cytokine receptors are known to signal through STAT family transcription factors , the mechanisms by which other cell-surface molecules , such as CD2 , transduce signals is unclear .", "annotated_text": "Although <protein>cytokine receptors</protein> are known to signal through <protein>STAT family transcription factors</protein> , the mechanisms by which other <protein>cell-surface molecules</protein> , such as <protein>CD2</protein> , transduce signals is unclear ."}
{"id": "2682", "text": "The goal of this study was to determine whether stimulation of T cells through CD2 recapitulates aspects of cytokine -induced T-cell activation by use of STAT transcription factors .", "annotated_text": "The goal of this study was to determine whether stimulation of <cell_type>T cells</cell_type> through <protein>CD2</protein> recapitulates aspects of <protein>cytokine</protein> -induced T-cell activation by use of <protein>STAT transcription factors</protein> ."}
{"id": "2683", "text": "MATERIALS AND METHODS : T cells were treated with anti-CD2 antibodies or cells bearing the natural CD2 ligand CD58 , after which signaling through STAT transcription factors was assessed .", "annotated_text": "MATERIALS AND METHODS : <cell_type>T cells</cell_type> were treated with <protein>anti-CD2 antibodies</protein> or cells bearing the natural <protein>CD2 ligand CD58</protein> , after which signaling through <protein>STAT transcription factors</protein> was assessed ."}
{"id": "2684", "text": "RESULTS : Stimulation of CD2 on primary T lymphocytes leads to the tyrosine phosphorylation , nuclear translocation , and DNA binding of STAT1 .", "annotated_text": "RESULTS : Stimulation of <protein>CD2</protein> on <cell_type>primary T lymphocytes</cell_type> leads to the tyrosine phosphorylation , nuclear translocation , and DNA binding of <protein>STAT1</protein> ."}
{"id": "2685", "text": "In contrast to stimulation by cytokines , the activation of STAT1 in response to CD2 ligation is delayed and does not involve Jak kinases .", "annotated_text": "In contrast to stimulation by <protein>cytokines</protein> , the activation of <protein>STAT1</protein> in response to CD2 ligation is delayed and does not involve <protein>Jak kinases</protein> ."}
{"id": "2686", "text": "Furthermore , while STAT phosphorylation induced by cytokines is generally transient , STAT1 phosphorylation following CD2 stimulation persists for a period of days .", "annotated_text": "Furthermore , while STAT phosphorylation induced by <protein>cytokines</protein> is generally transient , STAT1 phosphorylation following CD2 stimulation persists for a period of days ."}
{"id": "2687", "text": "Transcription of key target genes such as IRF1 and c-fos proceeds with delayed kinetics following CD2 stimulation , suggesting that this unique pattern of STAT activation may lead to a distinct cellular response following CD2 ligation .", "annotated_text": "Transcription of key target genes such as <dna>IRF1</dna> and <dna>c-fos</dna> proceeds with delayed kinetics following CD2 stimulation , suggesting that this unique pattern of STAT activation may lead to a distinct cellular response following CD2 ligation ."}
{"id": "2688", "text": "This pathway appears to be restricted to T cells , as stimulation of CD2 on NK cells does not lead to STAT1 activation .", "annotated_text": "This pathway appears to be restricted to <cell_type>T cells</cell_type> , as stimulation of <protein>CD2</protein> on <cell_type>NK cells</cell_type> does not lead to STAT1 activation ."}
{"id": "2689", "text": "CONCLUSION : Stimulation of T cells through cell-surface molecules such as CD2 involves activation of STAT transcription factors , thus recapitulating elements of cytokine signaling .", "annotated_text": "CONCLUSION : Stimulation of <cell_type>T cells</cell_type> through <protein>cell-surface molecules</protein> such as <protein>CD2</protein> involves activation of <protein>STAT transcription factors</protein> , thus recapitulating elements of cytokine signaling ."}
{"id": "2690", "text": "NFATc1 and NFATc2 together control both T and B cell activation and differentiation .", "annotated_text": "<protein>NFATc1</protein> and <protein>NFATc2</protein> together control both T and B cell activation and differentiation ."}
{"id": "2691", "text": "NFAT transcription factors play critical roles in gene transcription during immune responses .", "annotated_text": "<protein>NFAT transcription factors</protein> play critical roles in gene transcription during immune responses ."}
{"id": "2692", "text": "To investigate further the two most prominent NFAT family members , NFATc1 and NFATc2 , we generated mice bearing lymphoid systems devoid of both .", "annotated_text": "To investigate further the two most prominent <protein>NFAT family members</protein> , <protein>NFATc1</protein> and <protein>NFATc2</protein> , we generated mice bearing lymphoid systems devoid of both ."}
{"id": "2693", "text": "Doubly deficient T cells displayed cell surface markers of activation yet were significantly deficient in the development of multiple effector functions , including Th cytokine production , surface effector molecule expression , and cytolytic activity .", "annotated_text": "Doubly deficient <cell_type>T cells</cell_type> displayed cell surface markers of activation yet were significantly deficient in the development of multiple effector functions , including <protein>Th cytokine</protein> production , <protein>surface effector molecule</protein> expression , and cytolytic activity ."}
{"id": "2694", "text": "Nevertheless , doubly deficient B cells were hyperactivated , as evidenced by extremely elevated serum IgG1 and IgE , as well as plasma cell expansion and infiltration of end organs .", "annotated_text": "Nevertheless , <cell_type>doubly deficient B cells</cell_type> were hyperactivated , as evidenced by extremely elevated serum <protein>IgG1</protein> and <protein>IgE</protein> , as well as <cell_type>plasma cell</cell_type> expansion and infiltration of end organs ."}
{"id": "2695", "text": "Thus , in T cells , NFATc1 and NFATc2 are dispensable for inflammatory reactivity but are required for effector differentiation , while in B cells , NFATs regulate both normal homeostasis and differentiation .", "annotated_text": "Thus , in <cell_type>T cells</cell_type> , <protein>NFATc1</protein> and <protein>NFATc2</protein> are dispensable for inflammatory reactivity but are required for effector differentiation , while in <cell_type>B cells</cell_type> , <protein>NFATs</protein> regulate both normal homeostasis and differentiation ."}
{"id": "2696", "text": "Epstein-barr virus immediate-early protein BZLF1 is SUMO-1 modified and disrupts promyelocytic leukemia bodies .", "annotated_text": "Epstein-barr virus <protein>immediate-early protein BZLF1</protein> is SUMO-1 modified and disrupts promyelocytic leukemia bodies ."}
{"id": "2697", "text": "Although the immediate-early proteins of both herpes simplex virus ( HSV ) and cytomegalovirus ( CMV ) are known to modify promyelocytic leukemia ( PML ) ( ND10 ) bodies in the nucleus of the host cell , it has been unclear whether lytic infection with gamma herpesviruses induces a similar effect .", "annotated_text": "Although the <protein>immediate-early proteins</protein> of both herpes simplex virus ( HSV ) and cytomegalovirus ( CMV ) are known to modify promyelocytic leukemia ( PML ) ( ND10 ) bodies in the nucleus of the host cell , it has been unclear whether lytic infection with gamma herpesviruses induces a similar effect ."}
{"id": "2698", "text": "The PML protein is induced by interferon , involved in major histocompatibility complex class I presentation , and necessary for certain types of apoptosis .", "annotated_text": "The <protein>PML protein</protein> is induced by <protein>interferon</protein> , involved in <protein>major histocompatibility complex class I</protein> presentation , and necessary for certain types of apoptosis ."}
{"id": "2699", "text": "Therefore , it is likely that PML bodies function in an antiviral capacity .", "annotated_text": "Therefore , it is likely that PML bodies function in an antiviral capacity ."}
{"id": "2700", "text": "SUMO-1 modification of PML is known to be required for the formation of PML bodies .", "annotated_text": "SUMO-1 modification of <protein>PML</protein> is known to be required for the formation of PML bodies ."}
{"id": "2701", "text": "To examine whether Epstein-Barr virus ( EBV ) lytic replication interferes with PML bodies , we expressed the EBV immediate-early genes BZLF1 ( Z ) and BRLF1 ( R ) in EBV-positive cell lines and examined PML localization .", "annotated_text": "To examine whether Epstein-Barr virus ( EBV ) lytic replication interferes with PML bodies , we expressed the <dna>EBV immediate-early genes</dna> <dna>BZLF1 ( Z )</dna> and <dna>BRLF1 ( R )</dna> in <cell_line>EBV-positive cell lines</cell_line> and examined <protein>PML</protein> localization ."}
{"id": "2702", "text": "Both Z and R expression resulted in PML dispersion in EBV-positive cells .", "annotated_text": "Both Z and R expression resulted in <protein>PML</protein> dispersion in <cell_type>EBV-positive cells</cell_type> ."}
{"id": "2703", "text": "Z but not R expression is sufficient to disrupt PML bodies in EBV-negative cell lines .", "annotated_text": "Z but not R expression is sufficient to disrupt PML bodies in <cell_line>EBV-negative cell lines</cell_line> ."}
{"id": "2704", "text": "We show that dispersion of PML bodies by Z requires a portion of the transcriptional activation domain of Z but not the DNA-binding function .", "annotated_text": "We show that dispersion of PML bodies by <dna>Z</dna> requires a portion of the <dna>transcriptional activation domain</dna> of <dna>Z</dna> but not the DNA-binding function ."}
{"id": "2705", "text": "As was previously reported for the HSV-1 ICP0 and CMV IE1 proteins , Z reduces the amount of SUMO-1-modified PML .", "annotated_text": "As was previously reported for the <protein>HSV-1 ICP0 and CMV IE1 proteins</protein> , <dna>Z</dna> reduces the amount of <protein>SUMO-1-modified PML</protein> ."}
{"id": "2706", "text": "We also found that Z itself is SUMO-1 modified ( through amino acid 12 ) and that Z competes with PML for limiting amounts of SUMO-1 .", "annotated_text": "We also found that <dna>Z</dna> itself is SUMO-1 modified ( through amino acid 12 ) and that <dna>Z</dna> competes with <protein>PML</protein> for limiting amounts of <protein>SUMO-1</protein> ."}
{"id": "2707", "text": "These results suggest that disruption of PML bodies is important for efficient lytic replication of EBV .", "annotated_text": "These results suggest that disruption of PML bodies is important for efficient lytic replication of EBV ."}
{"id": "2708", "text": "Furthermore , Z may potentially alter the function of a variety of cellular proteins by inhibiting SUMO-1 modification", "annotated_text": "Furthermore , <dna>Z</dna> may potentially alter the function of a variety of cellular proteins by inhibiting SUMO-1 modification"}
{"id": "2709", "text": "Suppression of nuclear factor-kappaB and stimulation of inhibitor kappaB by troglitazone : evidence for an anti-inflammatory effect and a potential antiatherosclerotic effect in the obese .", "annotated_text": "Suppression of <protein>nuclear factor-kappaB</protein> and stimulation of <protein>inhibitor kappaB</protein> by troglitazone : evidence for an anti-inflammatory effect and a potential antiatherosclerotic effect in the obese ."}
{"id": "2710", "text": "To elucidate whether troglitazone exerts an antiinflammatory effect in humans , in vivo , we investigated the suppression of nuclear factor kappaB ( NFkappaB ) in mononuclear cells ( MNC ) by this drug .", "annotated_text": "To elucidate whether troglitazone exerts an antiinflammatory effect in humans , in vivo , we investigated the suppression of <protein>nuclear factor kappaB</protein> ( <protein>NFkappaB</protein> ) in <cell_type>mononuclear cells ( MNC )</cell_type> by this drug ."}
{"id": "2711", "text": "We measured intranuclear NFkappaB , total cellular NFkappaB , inhibitor kappaB ( IkappaB ) alpha , reactive oxygen species ( ROS ) generation , and p47 ( phox ) subunit ( a key component protein of nicotinamide adenine dinucleotide phosphate oxidase ) in MNC .", "annotated_text": "We measured <protein>intranuclear NFkappaB</protein> , total <protein>cellular NFkappaB</protein> , <protein>inhibitor kappaB ( IkappaB ) alpha</protein> , reactive oxygen species ( ROS ) generation , and <protein>p47 ( phox ) subunit</protein> ( a key component protein of <protein>nicotinamide adenine dinucleotide phosphate oxidase</protein> ) in <cell_type>MNC</cell_type> ."}
{"id": "2712", "text": "Plasma tumor necrosis factor ( TNF ) -alpha , soluble intercellular adhesion molecule-1 ( sICAM-1 ) , monocyte chemoattractant protein-1 ( MCP-1 ) , plasminogen activator inhibitor type 1 ( PAI-1 ) , C-reactive protein ( CRP ) , and interleukin ( IL ) -10 ( antiinflammatory cytokine ) concentrations were also measured as mediators of inflammatory activity that are regulated by the proinflammatory transcription factor NFkappaB .", "annotated_text": "<protein>Plasma tumor necrosis factor ( TNF ) -alpha</protein> , <protein>soluble intercellular adhesion molecule-1</protein> ( <protein>sICAM-1</protein> ) , <protein>monocyte chemoattractant protein-1 ( MCP-1 )</protein> , <protein>plasminogen activator inhibitor type 1</protein> ( <protein>PAI-1</protein> ) , <protein>C-reactive protein ( CRP )</protein> , and <protein>interleukin ( IL ) -10</protein> ( <protein>antiinflammatory cytokine</protein> ) concentrations were also measured as mediators of inflammatory activity that are regulated by the <protein>proinflammatory transcription factor NFkappaB</protein> ."}
{"id": "2713", "text": "Seven nondiabetic obese patients were given 400 mg troglitazone daily for 4 weeks .", "annotated_text": "Seven nondiabetic obese patients were given 400 mg troglitazone daily for 4 weeks ."}
{"id": "2714", "text": "Blood samples were collected before and at weekly intervals thereafter .", "annotated_text": "Blood samples were collected before and at weekly intervals thereafter ."}
{"id": "2715", "text": "MNC were separated ; and the levels of intranuclear NFkappaB , total cellular NFkappaB , IkappaBalpha , and p47 ( phox ) subunit and ROS generation were determined .", "annotated_text": "<cell_type>MNC</cell_type> were separated ; and the levels of <protein>intranuclear NFkappaB</protein> , total <protein>cellular NFkappaB</protein> , <protein>IkappaBalpha</protein> , and <protein>p47 ( phox ) subunit</protein> and ROS generation were determined ."}
{"id": "2716", "text": "Plasma was used to measure insulin glucose , TNFalpha , sICAM , MCP-1 , PAI-1 , CRP , and IL-10 .", "annotated_text": "Plasma was used to measure insulin glucose , <protein>TNFalpha</protein> , <protein>sICAM</protein> , <protein>MCP-1</protein> , <protein>PAI-1</protein> , <protein>CRP</protein> , and <protein>IL-10</protein> ."}
{"id": "2717", "text": "Plasma insulin concentrations fell significantly at week 1 , from 31.2 +/- 29.1 to 14.2 +/- 11.4 mU/L ( P < 0.01 ) and remained low throughout 4 weeks .", "annotated_text": "Plasma insulin concentrations fell significantly at week 1 , from 31.2 +/- 29.1 to 14.2 +/- 11.4 mU/L ( P < 0.01 ) and remained low throughout 4 weeks ."}
{"id": "2718", "text": "Plasma glucose concentrations did not alter significantly .", "annotated_text": "Plasma glucose concentrations did not alter significantly ."}
{"id": "2719", "text": "There was a fall in intranuclear NFkappaB , total cellular NFkappaB , and p47 ( phox ) subunit , with an increase in cellular IkappaBalpha at week 2 , which persisted until week 4 .", "annotated_text": "There was a fall in <protein>intranuclear NFkappaB</protein> , total <protein>cellular NFkappaB</protein> , and <protein>p47 ( phox ) subunit</protein> , with an increase in cellular <protein>IkappaBalpha</protein> at week 2 , which persisted until week 4 ."}
{"id": "2720", "text": "There was a parallel fall in ROS generation by MNC at week 1 ; this progressed and persisted until week 4 ( P < 0.001 ) .", "annotated_text": "There was a parallel fall in ROS generation by <cell_type>MNC</cell_type> at week 1 ; this progressed and persisted until week 4 ( P < 0.001 ) ."}
{"id": "2721", "text": "Plasma TNF-alpha , sICAM-1 , MCP-1 , and PAI-1 concentrations fell significantly at week 4 .", "annotated_text": "Plasma <protein>TNF-alpha</protein> , <protein>sICAM-1</protein> , <protein>MCP-1</protein> , and <protein>PAI-1</protein> concentrations fell significantly at week 4 ."}
{"id": "2722", "text": "Plasma IL-10 concentration increased significantly , whereas plasma CRP concentrations decreased .", "annotated_text": "Plasma <protein>IL-10</protein> concentration increased significantly , whereas <protein>plasma CRP</protein> concentrations decreased ."}
{"id": "2723", "text": "We conclude that troglitazone has an antiinflammatory action that may contribute to its putative antiatherosclerotic effects .", "annotated_text": "We conclude that troglitazone has an antiinflammatory action that may contribute to its putative antiatherosclerotic effects ."}
{"id": "2724", "text": "Tyrosine phosphorylation-dependent activation of NF-kappa B .", "annotated_text": "Tyrosine phosphorylation-dependent activation of <protein>NF-kappa B</protein> ."}
{"id": "2725", "text": "Requirement for p56 LCK and ZAP-70 protein tyrosine kinases .", "annotated_text": "Requirement for <protein>p56 LCK and ZAP-70 protein tyrosine kinases</protein> ."}
{"id": "2726", "text": "Phosphorylation of the N-terminal domain of I kappa B inhibitory subunits induces activation of the transcription factor NF-kappa B .", "annotated_text": "Phosphorylation of the <protein>N-terminal domain</protein> of <protein>I kappa B inhibitory subunits</protein> induces activation of the <protein>transcription factor NF-kappa B</protein> ."}
{"id": "2727", "text": "Although serine phosphorylation has been shown to induce ubiquitination and subsequent proteasome-mediated degradation of I kappa B-alpha , little is known about the mechanisms that lead to release of active NF-kappa B in T cells as a consequence of tyrosine phosphorylation of I kappa B-alpha [ Imbert , V. , Rupec , R.A. , Livolsi , A. , Pahl , H.L. , Traenckner , B.M. , Mueller-Dieckmann , C. , Farahifar , D. , Rossi , B. , Auberger , P. , Baeuerle , P. & Peyron , J.F. ( 1996 ) Cell 86 , 787 -- 798 ] .", "annotated_text": "Although serine phosphorylation has been shown to induce ubiquitination and subsequent proteasome-mediated degradation of <protein>I kappa B-alpha</protein> , little is known about the mechanisms that lead to release of active <protein>NF-kappa B</protein> in <cell_type>T cells</cell_type> as a consequence of tyrosine phosphorylation of <protein>I kappa B-alpha</protein> [ Imbert , V. , Rupec , R.A. , Livolsi , A. , Pahl , H.L. , Traenckner , B.M. , Mueller-Dieckmann , C. , Farahifar , D. , Rossi , B. , Auberger , P. , Baeuerle , P. & Peyron , J.F. ( 1996 ) Cell 86 , 787 -- 798 ] ."}
{"id": "2728", "text": "The involvement of the tyrosine kinases p56 ( lck ) and ZAP-70 in this reaction is demonstrated here using specific pharmacological inhibitors and Jurkat mutants unable to express these kinases .", "annotated_text": "The involvement of the <protein>tyrosine kinases</protein> <protein>p56 ( lck )</protein> and <protein>ZAP-70</protein> in this reaction is demonstrated here using specific pharmacological inhibitors and <cell_line>Jurkat mutants</cell_line> unable to express these <protein>kinases</protein> ."}
{"id": "2729", "text": "Although the inhibitors prevented both pervanadate-induced phosphorylation of I kappa B-alpha on Tyr42 and NF-kappa B activation , we observed that , in p56 ( lck ) -deficient Jurkat mutants , NF-kappa B could still associate with I kappa B-alpha despite phosphorylation on Tyr42 .", "annotated_text": "Although the inhibitors prevented both pervanadate-induced phosphorylation of <protein>I kappa B-alpha</protein> on Tyr42 and <protein>NF-kappa B</protein> activation , we observed that , in <cell_line>p56 ( lck ) -deficient Jurkat mutants</cell_line> , <protein>NF-kappa B</protein> could still associate with <protein>I kappa B-alpha</protein> despite phosphorylation on Tyr42 ."}
{"id": "2730", "text": "Furthermore , the SH2 domain of p56 ( lck ) appeared to be required for pervanadate-induced NF-kappa B activation but not for Tyr42 phosphorylation .", "annotated_text": "Furthermore , the <protein>SH2 domain</protein> of <protein>p56 ( lck )</protein> appeared to be required for pervanadate-induced <protein>NF-kappa B</protein> activation but not for Tyr42 phosphorylation ."}
{"id": "2731", "text": "These results show that p56 ( lck ) and ZAP-70 are key components of the signaling pathway that leads to phosphotyrosine-dependent NF-kappa B activation in T cells and confirm that tyrosine kinases must control at least two different steps to induce activation of NF-kappa B .", "annotated_text": "These results show that <protein>p56 ( lck )</protein> and <protein>ZAP-70</protein> are key components of the signaling pathway that leads to phosphotyrosine-dependent <protein>NF-kappa B</protein> activation in <cell_type>T cells</cell_type> and confirm that <protein>tyrosine kinases</protein> must control at least two different steps to induce activation of <protein>NF-kappa B</protein> ."}
{"id": "2732", "text": "Finally , we show that H ( 2 ) O ( 2 ) , which stimulates p56 ( lck ) and ZAP-70 in T cells , is an activator of NF-kappa B through tyrosine phosphorylation of I kappa B-alpha .", "annotated_text": "Finally , we show that H ( 2 ) O ( 2 ) , which stimulates <protein>p56 ( lck )</protein> and <protein>ZAP-70</protein> in <cell_type>T cells</cell_type> , is an activator of <protein>NF-kappa B</protein> through tyrosine phosphorylation of <protein>I kappa B-alpha</protein> ."}
{"id": "2733", "text": "Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia .", "annotated_text": "Specific missense mutations in <dna>NEMO</dna> result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia ."}
{"id": "2734", "text": "The gene that encodes nuclear factor kappaB ( NF-kappaB ) essential modulator ( or NEMO , also known as IKKgamma ) is required for activation of the transcription factor NF-kappaB .", "annotated_text": "The gene that encodes <dna>nuclear factor kappaB ( NF-kappaB ) essential modulator</dna> ( or <dna>NEMO</dna> , also known as <dna>IKKgamma</dna> ) is required for activation of the <protein>transcription factor NF-kappaB</protein> ."}
{"id": "2735", "text": "We describe mutations in the putative zinc-finger domain of NEMO that result in an X-linked primary immunodeficiency characterized by hyper-IgM syndrome and hypohydrotic ectodermal dysplasia ( XHM-ED ) .", "annotated_text": "We describe mutations in the <protein>putative zinc-finger domain</protein> of <protein>NEMO</protein> that result in an X-linked primary immunodeficiency characterized by hyper-IgM syndrome and hypohydrotic ectodermal dysplasia ( XHM-ED ) ."}
{"id": "2736", "text": "These mutations prevent CD40 ligand ( CD40L ) -mediated degradation of inhibitor of NF-kappaB alpha ( IkappaB-alpha ) and account for the following observations : B cells from XHM-ED patients are unable to undergo immunoglobulin class-switch recombination and antigen-presenting cells ( APCs ) are unable to synthesize the NF-kappaB-regulated cytokines interleukin 12 ( IL-12 ) or tumor necrosis factor alpha ( TNF-alpha ) when stimulated with CD40L .", "annotated_text": "These mutations prevent <protein>CD40 ligand</protein> ( <protein>CD40L</protein> ) -mediated degradation of inhibitor of <protein>NF-kappaB alpha</protein> ( <protein>IkappaB-alpha</protein> ) and account for the following observations : <cell_type>B cells</cell_type> from XHM-ED patients are unable to undergo immunoglobulin class-switch recombination and <cell_type>antigen-presenting cells</cell_type> ( <cell_type>APCs</cell_type> ) are unable to synthesize the <protein>NF-kappaB-regulated cytokines</protein> <protein>interleukin 12</protein> ( <protein>IL-12</protein> ) or <protein>tumor necrosis factor alpha</protein> ( <protein>TNF-alpha</protein> ) when stimulated with <protein>CD40L</protein> ."}
{"id": "2737", "text": "Nevertheless , innate immunity is preserved in XHM-ED patients because APCs retain the capacity to respond to stimulation by lipopolysaccharide or Staphylococcus aureus Cowan 's antigen ( SAC ) .", "annotated_text": "Nevertheless , innate immunity is preserved in XHM-ED patients because <cell_type>APCs</cell_type> retain the capacity to respond to stimulation by lipopolysaccharide or <protein>Staphylococcus aureus Cowan 's antigen</protein> ( <protein>SAC</protein> ) ."}
{"id": "2738", "text": "Overall , the phenotype observed in XHM-ED patients shows that the putative zinc-finger domain of NEMO has a regulatory function and demonstrates the definite requirement of CD40 -mediated NF-kappaB activation for B cell immunoglobulin class-switching .", "annotated_text": "Overall , the phenotype observed in XHM-ED patients shows that the <protein>putative zinc-finger domain</protein> of <protein>NEMO</protein> has a regulatory function and demonstrates the definite requirement of <protein>CD40</protein> -mediated NF-kappaB activation for <cell_type>B cell</cell_type> immunoglobulin class-switching ."}
{"id": "2739", "text": "Granulocytic differentiation of human NB4 promyelocytic leukemia cells induced by all-trans retinoic acid metabolites .", "annotated_text": "Granulocytic differentiation of <cell_type>human NB4 promyelocytic leukemia cells</cell_type> induced by all-trans retinoic acid metabolites ."}
{"id": "2740", "text": "The metabolism of all-trans retinoic acid ( ATRA ) has been reported to be partly responsible for the in vivo resistance to ATRA seen in the treatment of human acute promyelocytic leukemia ( APL ) .", "annotated_text": "The metabolism of all-trans retinoic acid ( ATRA ) has been reported to be partly responsible for the in vivo resistance to ATRA seen in the treatment of human acute promyelocytic leukemia ( APL ) ."}
{"id": "2741", "text": "However , ATRA metabolism appears to be involved in the growth inhibition of several cancer cell lines in vitro .", "annotated_text": "However , ATRA metabolism appears to be involved in the growth inhibition of several <cell_line>cancer cell lines</cell_line> in vitro ."}
{"id": "2742", "text": "The purpose of this study was to evaluate the in vitro activity of the principal metabolites of ATRA [ 4-hydroxy-retinoic acid ( 4-OH-RA ) , 18-hydroxy-retinoic acid ( 18-OH-RA ) , 4-oxo-retinoic acid ( 4-oxo-RA ) , and 5 , 6-epoxy-retinoic acid ( 5 , 6-epoxy-RA ) ] in NB4 , a human promyelocytic leukemia cell line that exhibits the APL diagnostic t ( 15 ; 17 ) chromosomal translocation and expresses the PML-RAR alpha fusion protein .", "annotated_text": "The purpose of this study was to evaluate the in vitro activity of the principal metabolites of ATRA [ 4-hydroxy-retinoic acid ( 4-OH-RA ) , 18-hydroxy-retinoic acid ( 18-OH-RA ) , 4-oxo-retinoic acid ( 4-oxo-RA ) , and 5 , 6-epoxy-retinoic acid ( 5 , 6-epoxy-RA ) ] in <cell_line>NB4 , a human promyelocytic leukemia cell line</cell_line> that exhibits the APL diagnostic t ( 15 ; 17 ) chromosomal translocation and expresses the <protein>PML-RAR alpha fusion protein</protein> ."}
{"id": "2743", "text": "We established that the four ATRA metabolites were indeed formed by the NB4 cells in vitro .", "annotated_text": "We established that the four ATRA metabolites were indeed formed by the <cell_line>NB4 cells</cell_line> in vitro ."}
{"id": "2744", "text": "NB4 cell growth was inhibited ( 69-78 % at 120 h ) and cell cycle progression in the G1 phase ( 82-85 % at 120 h ) was blocked by ATRA and all of the metabolites at 1 microM concentration .", "annotated_text": "NB4 cell growth was inhibited ( 69-78 % at 120 h ) and cell cycle progression in the G1 phase ( 82-85 % at 120 h ) was blocked by ATRA and all of the metabolites at 1 microM concentration ."}
{"id": "2745", "text": "ATRA and its metabolites could induce NB4 cells differentiation with similar activity , as evaluated by cell morphology , by the nitroblue tetrazolium reduction test ( 82-88 % at 120 h ) or by the expression of the maturation specific cell surface marker CD11c .", "annotated_text": "ATRA and its metabolites could induce <cell_line>NB4 cells</cell_line> differentiation with similar activity , as evaluated by cell morphology , by the nitroblue tetrazolium reduction test ( 82-88 % at 120 h ) or by the expression of the <protein>maturation specific cell surface marker CD11c</protein> ."}
{"id": "2746", "text": "In addition , nuclear body reorganization to macropunctated structures , as well as the degradation of PML-RAR alpha , was found to be similar for ATRA and all of its metabolites .", "annotated_text": "In addition , nuclear body reorganization to macropunctated structures , as well as the degradation of <protein>PML-RAR alpha</protein> , was found to be similar for ATRA and all of its metabolites ."}
{"id": "2747", "text": "Comparison of the relative potency of the retinoids using the nitroblue tetrazolium reduction test showed effective concentrations required to differentiate 50 % of cells in 72 h as follows : ATRA , 15.8 +/- 1.7 nM ; 4-oxo-RA , 38.3 +/- 1.3 nM ; 18-OH-RA , 55.5 +/- 1.8 nM ; 4-OH-RA , 79.8 +/- 1.8 nM ; and 5 , 6-epoxy-RA , 99.5 +/- 1.5 nM .", "annotated_text": "Comparison of the relative potency of the retinoids using the nitroblue tetrazolium reduction test showed effective concentrations required to differentiate 50 % of cells in 72 h as follows : ATRA , 15.8 +/- 1.7 nM ; 4-oxo-RA , 38.3 +/- 1.3 nM ; 18-OH-RA , 55.5 +/- 1.8 nM ; 4-OH-RA , 79.8 +/- 1.8 nM ; and 5 , 6-epoxy-RA , 99.5 +/- 1.5 nM ."}
{"id": "2748", "text": "The ATRA metabolites were found to exert their differentiation effects via the RAR alpha nuclear receptors , because the RAR alpha-specific antagonist BMS614 blocked metabolite-induced CD11c expression in NB4 cells .", "annotated_text": "The ATRA metabolites were found to exert their differentiation effects via the <protein>RAR alpha nuclear receptors</protein> , because the RAR alpha-specific antagonist BMS614 blocked metabolite-induced CD11c expression in <cell_line>NB4 cells</cell_line> ."}
{"id": "2749", "text": "These data demonstrate that the principal ATRA Phase 1 metabolites can elicit leukemia cell growth inhibition and differentiation in vitro through the RAR alpha signaling pathway , and they suggest that these metabolites may play a role in ATRA antileukemic activity in vivo .", "annotated_text": "These data demonstrate that the principal ATRA Phase 1 metabolites can elicit <cell_type>leukemia cell</cell_type> growth inhibition and differentiation in vitro through the RAR alpha signaling pathway , and they suggest that these metabolites may play a role in ATRA antileukemic activity in vivo ."}
{"id": "2750", "text": "Expression of oestrogen and progesterone receptors by mast cells alone , but not lymphocytes , macrophages or other immune cells in human upper airways .", "annotated_text": "Expression of <protein>oestrogen and progesterone receptors</protein> by <cell_type>mast cells</cell_type> alone , but not <cell_type>lymphocytes</cell_type> , <cell_type>macrophages</cell_type> or other <cell_type>immune cells</cell_type> in human upper airways ."}
{"id": "2751", "text": "BACKGROUND : Nasal polyposis often coexists with asthma in airway inflammatory conditions characterised by the infiltration of a range of immune cells .", "annotated_text": "BACKGROUND : Nasal polyposis often coexists with asthma in airway inflammatory conditions characterised by the infiltration of a range of <cell_type>immune cells</cell_type> ."}
{"id": "2752", "text": "A potentially important role for ovarian hormones has been implicated in airway inflammation but the cellular target for such action is not known .", "annotated_text": "A potentially important role for ovarian hormones has been implicated in airway inflammation but the cellular target for such action is not known ."}
{"id": "2753", "text": "METHODS : Expression of oestrogen receptors ( ER ) and progesterone receptors ( PR ) was examined using immunohistochemistry in formalin fixed nasal polyp tissues from 47 subjects .", "annotated_text": "METHODS : Expression of <protein>oestrogen receptors</protein> ( <protein>ER</protein> ) and <protein>progesterone receptors</protein> ( <protein>PR</protein> ) was examined using immunohistochemistry in formalin fixed nasal polyp tissues from 47 subjects ."}
{"id": "2754", "text": "The cells positive for ER or PR were confirmed by spatial location , dual immunolabelling , and histochemical staining .", "annotated_text": "The cells positive for <protein>ER</protein> or <protein>PR</protein> were confirmed by spatial location , dual immunolabelling , and histochemical staining ."}
{"id": "2755", "text": "RESULTS : Consistent with the known features of nasal polyps , CD4+ ( T helper/inducer ) , CD8+ ( cytotoxic/suppressor ) , CD68+ ( macrophages ) , mast cells , eosinophils and neutrophils were all clearly detected by their relevant monoclonal antibodies or appropriate histochemical staining , but only mast cells tested positive for ER /PR labelling with their polyclonal and monoclonal antibodies .", "annotated_text": "RESULTS : Consistent with the known features of nasal polyps , <cell_type>CD4+ ( T helper/inducer )</cell_type> , <cell_type>CD8+ ( cytotoxic/suppressor )</cell_type> , <cell_type>CD68+</cell_type> ( <cell_type>macrophages</cell_type> ) , <cell_type>mast cells</cell_type> , <cell_type>eosinophils</cell_type> and <cell_type>neutrophils</cell_type> were all clearly detected by their relevant <protein>monoclonal antibodies</protein> or appropriate histochemical staining , but only <cell_type>mast cells</cell_type> tested positive for <protein>ER</protein> /PR labelling with their <protein>polyclonal and monoclonal antibodies</protein> ."}
{"id": "2756", "text": "The frequencies for expression were 61.7 % for ER positive and 59.6 % for PR positive cells .", "annotated_text": "The frequencies for expression were 61.7 % for <cell_type>ER positive</cell_type> and 59.6 % for <cell_type>PR positive cells</cell_type> ."}
{"id": "2757", "text": "The expression of ER / PR was independent of patient sex and age but was highly correlated with the numbers of mast cells ( r = 0.973 , p < 0.001 for ER ; r = 0.955 , p < 0.001 for PR ) .", "annotated_text": "The expression of <protein>ER</protein> / <protein>PR</protein> was independent of patient sex and age but was highly correlated with the numbers of <cell_type>mast cells</cell_type> ( r = 0.973 , p < 0.001 for <protein>ER</protein> ; r = 0.955 , p < 0.001 for <protein>PR</protein> ) ."}
{"id": "2758", "text": "Fewer than 5 % of mast cells were found to be negative for ER / PR expression .", "annotated_text": "Fewer than 5 % of <cell_type>mast cells</cell_type> were found to be negative for <protein>ER</protein> / <protein>PR</protein> expression ."}
{"id": "2759", "text": "CONCLUSIONS : Mast cells alone , but not lymphocytes , macrophages , or other immune cells , express ER / PR in human upper airways .", "annotated_text": "CONCLUSIONS : <cell_type>Mast cells</cell_type> alone , but not <cell_type>lymphocytes</cell_type> , <cell_type>macrophages</cell_type> , or other <cell_type>immune cells</cell_type> , express <protein>ER</protein> / <protein>PR</protein> in human upper airways ."}
{"id": "2760", "text": "Numerous ER/PR positive mast cells exist in nasal polyps , indicating that this may be a major route for the involvement of sex hormones in airway inflammation when exposed to the higher and varying concentration of oestrogen and progesterone characteristic of females .", "annotated_text": "Numerous <cell_type>ER/PR positive mast cells</cell_type> exist in nasal polyps , indicating that this may be a major route for the involvement of sex hormones in airway inflammation when exposed to the higher and varying concentration of oestrogen and progesterone characteristic of females ."}
{"id": "2761", "text": "NF kappa b signaling in posthypoxic endothelial cells : relevance to E-selectin expression and neutrophil adhesion .", "annotated_text": "NF kappa b signaling in <cell_type>posthypoxic endothelial cells</cell_type> : relevance to E-selectin expression and neutrophil adhesion ."}
{"id": "2762", "text": "Our previous studies have implicated the nuclear transcription factor kappa B ( NF kappa B ) in the regulation of adhesion molecule expression in endothelial cells exposed to anoxia-reoxygenation ( A/R ) or a redox imbalance .", "annotated_text": "Our previous studies have implicated the nuclear transcription factor kappa B ( <protein>NF kappa B</protein> ) in the regulation of <protein>adhesion molecule</protein> expression in <cell_type>endothelial cells</cell_type> exposed to anoxia-reoxygenation ( A/R ) or a redox imbalance ."}
{"id": "2763", "text": "The objectives of this study were ( 1 ) to define the kinetics of NF kappa B activation by examining I kappa B alpha degradation and the nuclear translocation of p65 in response to A/R or redox imbalance ( induced by treatment of cells with diamide and buthionine sulfoximine ) and ( 2 ) to determine whether the signal for I kappa B alpha degradation , nuclear translocation of p65 , and E-selectin -mediated neutrophil adhesion is related to the activity of protein tyrosine kinase ( PTK ) , protein tyrosine phosphatase ( PTPase ) and/or protein kinase C ( PKC ) .", "annotated_text": "The objectives of this study were ( 1 ) to define the kinetics of <protein>NF kappa B</protein> activation by examining I kappa B alpha degradation and the nuclear translocation of <protein>p65</protein> in response to A/R or redox imbalance ( induced by treatment of cells with diamide and buthionine sulfoximine ) and ( 2 ) to determine whether the signal for I kappa B alpha degradation , nuclear translocation of <protein>p65</protein> , and <protein>E-selectin</protein> -mediated neutrophil adhesion is related to the activity of <protein>protein tyrosine kinase</protein> ( <protein>PTK</protein> ) , <protein>protein tyrosine phosphatase</protein> ( <protein>PTPase</protein> ) and/or <protein>protein kinase C</protein> ( <protein>PKC</protein> ) ."}
{"id": "2764", "text": "The results demonstrate that both A/R and redox imbalance led to I kappa B alpha degradation within 30 min and the concomitant appearance of p65 in the nucleus , consistent with rapid cytosolic activation of NF kappa B and subsequent nuclear translocation of the activated p65 subunit .", "annotated_text": "The results demonstrate that both A/R and redox imbalance led to I kappa B alpha degradation within 30 min and the concomitant appearance of <protein>p65</protein> in the nucleus , consistent with rapid cytosolic activation of <protein>NF kappa B</protein> and subsequent nuclear translocation of the <protein>activated p65 subunit</protein> ."}
{"id": "2765", "text": "Inhibition of PKC blocked I kappa B alpha degradation and p65 translocation in A/R-challenged , but not redox-altered , endothelial cells .", "annotated_text": "Inhibition of <protein>PKC</protein> blocked <protein>I kappa B alpha</protein> degradation and <protein>p65</protein> translocation in A/R-challenged , but not redox-altered , <cell_type>endothelial cells</cell_type> ."}
{"id": "2766", "text": "However , both A/R- and redox-induced NF kappa B activation was blocked by inhibition of PTK .", "annotated_text": "However , both A/R- and redox-induced NF kappa B activation was blocked by inhibition of <protein>PTK</protein> ."}
{"id": "2767", "text": "Similarly , A/R-induced E-selectin expression and neutrophil-endothelial cell adhesion were blocked by inhibition of PKC or PTK , while only PTK inhibited the redox-induced adhesion response .", "annotated_text": "Similarly , A/R-induced E-selectin expression and neutrophil-endothelial cell adhesion were blocked by inhibition of <protein>PKC</protein> or <protein>PTK</protein> , while only <protein>PTK</protein> inhibited the redox-induced adhesion response ."}
{"id": "2768", "text": "Pretreatment of cells with N-acetyl cysteine effectively blocked A/R- or redox-induced I kappa B degradation and significantly attenuated the respective neutrophil adhesion responses .", "annotated_text": "Pretreatment of cells with N-acetyl cysteine effectively blocked A/R- or redox-induced I kappa B degradation and significantly attenuated the respective neutrophil adhesion responses ."}
{"id": "2769", "text": "Collectively , these findings indicate that A/R-induced E-selectin expression and neutrophil-endothelial cell adhesion are mediated by both PKC and PTK , which signal rapid activation of NF kappa B .", "annotated_text": "Collectively , these findings indicate that A/R-induced E-selectin expression and neutrophil-endothelial cell adhesion are mediated by both <protein>PKC</protein> and <protein>PTK</protein> , which signal rapid activation of <protein>NF kappa B</protein> ."}
{"id": "2770", "text": "This A/R-induced NF kappa B signaling response appears to be mediated , at least in part , by intracellular redox imbalance .", "annotated_text": "This A/R-induced <protein>NF kappa B</protein> signaling response appears to be mediated , at least in part , by intracellular redox imbalance ."}
{"id": "2771", "text": "Copyright 2001 S. Karger AG , Basel", "annotated_text": "Copyright 2001 S. Karger AG , Basel"}
{"id": "2772", "text": "Induction of apoptosis in human lymphocytes by the herbicide 2 , 4-dichlorophenoxyacetic acid .", "annotated_text": "Induction of apoptosis in <cell_type>human lymphocytes</cell_type> by the herbicide 2 , 4-dichlorophenoxyacetic acid ."}
{"id": "2773", "text": "Dimethylammonium salt of 2 , 4-dichlorophenoxyacetic acid ( DMA-2 , 4-D ) is a widely used herbicide that is considered moderately toxic .", "annotated_text": "Dimethylammonium salt of 2 , 4-dichlorophenoxyacetic acid ( DMA-2 , 4-D ) is a widely used herbicide that is considered moderately toxic ."}
{"id": "2774", "text": "In the present study we found that DMA-2 , 4-D is able to cause apoptosis in peripheral blood lymphocytes of healthy individuals and Jurkat T cells .", "annotated_text": "In the present study we found that DMA-2 , 4-D is able to cause apoptosis in <cell_type>peripheral blood lymphocytes</cell_type> of healthy individuals and <cell_line>Jurkat T cells</cell_line> ."}
{"id": "2775", "text": "Apoptosis induced by DMA-2 , 4-D was dose and time dependent , independent of Fas , TNF receptor 1 or the aromatic hydrocarbon receptor , and involved disruption of the mitochondrial transmembrane potential and activation of caspase-9 .", "annotated_text": "Apoptosis induced by DMA-2 , 4-D was dose and time dependent , independent of <protein>Fas</protein> , <protein>TNF receptor 1</protein> or the <protein>aromatic hydrocarbon receptor</protein> , and involved disruption of the mitochondrial transmembrane potential and activation of <protein>caspase-9</protein> ."}
{"id": "2776", "text": "ZVAD-FMK , a broad-spectrum inhibitor of caspases , blocked DMA-2 , 4-D-induced apoptosis completely .", "annotated_text": "ZVAD-FMK , a broad-spectrum inhibitor of <protein>caspases</protein> , blocked DMA-2 , 4-D-induced apoptosis completely ."}
{"id": "2777", "text": "While an inhibitor of caspase-9 , as well as caspase-9 and caspase-3 inhibitors in combination , strongly blocked DMA-2 , 4-D-induced apoptosis , an inhibitor of caspase-3 had a moderate inhibitory effect .", "annotated_text": "While an inhibitor of <protein>caspase-9</protein> , as well as <protein>caspase-9</protein> and caspase-3 inhibitors in combination , strongly blocked DMA-2 , 4-D-induced apoptosis , an inhibitor of <protein>caspase-3</protein> had a moderate inhibitory effect ."}
{"id": "2778", "text": "Unlike Fas -mediated apoptosis , the initiator caspase , caspase-8 , was not involved in DMA-2 , 4-D-induced apoptosis .", "annotated_text": "Unlike <protein>Fas</protein> -mediated apoptosis , the <protein>initiator caspase</protein> , <protein>caspase-8</protein> , was not involved in DMA-2 , 4-D-induced apoptosis ."}
{"id": "2779", "text": "Transfection of Jurkat cells with Bcl-2 prevented DMA-2 , 4-D-induced disruption of the mitochondrial transmembrane potential and led to a complete blockage of apoptosis .", "annotated_text": "Transfection of <cell_line>Jurkat cells</cell_line> with <protein>Bcl-2</protein> prevented DMA-2 , 4-D-induced disruption of the mitochondrial transmembrane potential and led to a complete blockage of apoptosis ."}
{"id": "2780", "text": "Our data indicate that DMA-2 , 4-D kills human lymphocytes by initiating apoptosis via a direct effect on mitochondria .", "annotated_text": "Our data indicate that DMA-2 , 4-D kills <cell_type>human lymphocytes</cell_type> by initiating apoptosis via a direct effect on mitochondria ."}
{"id": "2781", "text": "The activation of caspases occurs downstream of mitochondrial damage , and the dysfunction of mitochondria appears to be sufficient for triggering all downstream events leading to apoptosis .", "annotated_text": "The activation of <protein>caspases</protein> occurs downstream of mitochondrial damage , and the dysfunction of mitochondria appears to be sufficient for triggering all downstream events leading to apoptosis ."}
{"id": "2782", "text": "Inhibition of Th1 differentiation by IL-6 is mediated by SOCS1 .", "annotated_text": "Inhibition of Th1 differentiation by <protein>IL-6</protein> is mediated by <protein>SOCS1</protein> ."}
{"id": "2783", "text": "Interleukin 6 ( IL-6 ) is a cytokine produced by immune and nonimmune cells and exhibits functional pleiotropy and redundancy .", "annotated_text": "<protein>Interleukin 6</protein> ( <protein>IL-6</protein> ) is a <protein>cytokine</protein> produced by <cell_type>immune and nonimmune cells</cell_type> and exhibits functional pleiotropy and redundancy ."}
{"id": "2784", "text": "IL-6 plays an important role in the differentiation of several cell types .", "annotated_text": "<protein>IL-6</protein> plays an important role in the differentiation of several cell types ."}
{"id": "2785", "text": "Here , we describe a novel function of IL-6 : the negative regulation of CD4 + Th1 cell differentiation .", "annotated_text": "Here , we describe a novel function of <protein>IL-6</protein> : the negative regulation of <protein>CD4</protein> + Th1 cell differentiation ."}
{"id": "2786", "text": "While IL-6 -directed CD4 + Th2 differentiation is mediated by IL-4 , inhibition of Th1 differentiation by IL-6 is independent of IL-4 .", "annotated_text": "While <protein>IL-6</protein> -directed <protein>CD4</protein> + Th2 differentiation is mediated by <protein>IL-4</protein> , inhibition of Th1 differentiation by <protein>IL-6</protein> is independent of <protein>IL-4</protein> ."}
{"id": "2787", "text": "IL-6 upregulates suppressor of cytokine signaling 1 ( SOCS1 ) expression in activated CD4+ T cells , thereby interfering with signal transducer and activator of transcription 1 ( STAT1 ) phosphorylation induced by interferon gamma ( IFNgamma ) .", "annotated_text": "<protein>IL-6</protein> upregulates <protein>suppressor of cytokine signaling 1</protein> ( <protein>SOCS1</protein> ) expression in <cell_type>activated CD4+ T cells</cell_type> , thereby interfering with <protein>signal transducer and activator of transcription 1</protein> ( <protein>STAT1</protein> ) phosphorylation induced by <protein>interferon gamma</protein> ( <protein>IFNgamma</protein> ) ."}
{"id": "2788", "text": "Inhibition of IFNgamma receptor-mediated signals by IL-6 prevents autoregulation of IFNgamma gene expression by IFNgamma during CD4+ T cell activation , thereby preventing Th1 differentiation .", "annotated_text": "Inhibition of <protein>IFNgamma</protein> receptor-mediated signals by <protein>IL-6</protein> prevents autoregulation of <dna>IFNgamma gene</dna> expression by <protein>IFNgamma</protein> during <cell_type>CD4+ T cell</cell_type> activation , thereby preventing Th1 differentiation ."}
{"id": "2789", "text": "Thus , IL-6 promotes CD4 + Th2 differentiation and inhibits Th1 differentiation by two independent molecular mechanisms .", "annotated_text": "Thus , <protein>IL-6</protein> promotes <protein>CD4</protein> + Th2 differentiation and inhibits Th1 differentiation by two independent molecular mechanisms ."}
{"id": "2790", "text": "Interaction between CCAAT/enhancer binding protein and cyclic AMP response element binding protein 1 regulates human immunodeficiency virus type 1 transcription in cells of the monocyte/macrophage lineage .", "annotated_text": "Interaction between <protein>CCAAT/enhancer binding protein</protein> and <protein>cyclic AMP response element binding protein 1</protein> regulates human immunodeficiency virus type 1 transcription in cells of the <cell_type>monocyte/macrophage lineage</cell_type> ."}
{"id": "2791", "text": "Recent observations have shown two CCAAT/enhancer binding protein ( C/EBP ) binding sites to be critically important for efficient human immunodeficiency virus type 1 ( HIV-1 ) replication within cells of the monocyte/macrophage lineage , a cell type likely involved in transport of the virus to the brain .", "annotated_text": "Recent observations have shown two <dna>CCAAT/enhancer binding protein ( C/EBP ) binding sites</dna> to be critically important for efficient human immunodeficiency virus type 1 ( HIV-1 ) replication within cells of the <cell_type>monocyte/macrophage lineage</cell_type> , a cell type likely involved in transport of the virus to the brain ."}
{"id": "2792", "text": "Additionally , sequence variation at C/EBP site I , which lies immediately upstream of the distal nuclear factor kappa B site and immediately downstream of a binding site for activating transcription factor ( ATF ) / cyclic AMP response element binding protein ( CREB ) , has been shown to affect HIV-1 long terminal repeat ( LTR ) activity .", "annotated_text": "Additionally , sequence variation at <dna>C/EBP site I</dna> , which lies immediately upstream of the <dna>distal nuclear factor kappa B site</dna> and immediately downstream of a binding site for <protein>activating transcription factor</protein> ( <protein>ATF</protein> ) / <protein>cyclic AMP response element binding protein</protein> ( <protein>CREB</protein> ) , has been shown to affect <dna>HIV-1 long terminal repeat</dna> ( <dna>LTR</dna> ) activity ."}
{"id": "2793", "text": "Given that C/EBP proteins have been shown to interact with many other transcription factors including members of the ATF/CREB family , we proceeded to determine whether an adjacent ATF/CREB binding site could affect C/EBP protein binding to C/EBP site I .", "annotated_text": "Given that <protein>C/EBP proteins</protein> have been shown to interact with many other <protein>transcription factors</protein> including members of the <protein>ATF/CREB family</protein> , we proceeded to determine whether an adjacent <dna>ATF/CREB binding site</dna> could affect <protein>C/EBP protein</protein> binding to <dna>C/EBP site I</dna> ."}
{"id": "2794", "text": "Electrophoretic mobility shift analyses indicated that selected ATF/CREB site variants assisted in the recruitment of C/EBP proteins to an adjacent , naturally occurring , low-affinity C/EBP site .", "annotated_text": "Electrophoretic mobility shift analyses indicated that selected <dna>ATF/CREB site variants</dna> assisted in the recruitment of <protein>C/EBP proteins</protein> to an adjacent , naturally occurring , low-affinity <dna>C/EBP site</dna> ."}
{"id": "2795", "text": "This biophysical interaction appears to occur via at least two mechanisms .", "annotated_text": "This biophysical interaction appears to occur via at least two mechanisms ."}
{"id": "2796", "text": "First , low amounts of CREB-1 and C/EBP appear to heterodimerize and bind to a site consisting of a half site from both the ATF/CREB and C/EBP binding sites .", "annotated_text": "First , low amounts of <protein>CREB-1</protein> and <protein>C/EBP</protein> appear to heterodimerize and bind to a site consisting of a half site from both the <dna>ATF/CREB and C/EBP binding sites</dna> ."}
{"id": "2797", "text": "In addition , CREB-1 homodimers bind to the ATF/CREB site and recruit C/EBP dimers to their cognate weak binding sites .", "annotated_text": "In addition , <protein>CREB-1 homodimers</protein> bind to the <dna>ATF/CREB site</dna> and recruit <protein>C/EBP dimers</protein> to their cognate <dna>weak binding sites</dna> ."}
{"id": "2798", "text": "This interaction is reciprocal , since C/EBP dimer binding to a strong C/EBP site leads to enhanced CREB-1 recruitment to ATF/CREB sites that are weakly bound by CREB .", "annotated_text": "This interaction is reciprocal , since <protein>C/EBP dimer</protein> binding to a strong <dna>C/EBP site</dna> leads to enhanced <protein>CREB-1</protein> recruitment to <dna>ATF/CREB sites</dna> that are weakly bound by <protein>CREB</protein> ."}
{"id": "2799", "text": "Sequence variation at both C/EBP and ATF/CREB sites affects the molecular interactions involved in mediating both of these mechanisms .", "annotated_text": "Sequence variation at both <dna>C/EBP and ATF/CREB sites</dna> affects the molecular interactions involved in mediating both of these mechanisms ."}
{"id": "2800", "text": "Most importantly , sequence variation at the ATF/CREB binding site affected basal LTR activity as well as LTR function following interleukin-6 stimulation , a treatment that leads to increases in C/EBP activation .", "annotated_text": "Most importantly , sequence variation at the <dna>ATF/CREB binding site</dna> affected basal <dna>LTR</dna> activity as well as <dna>LTR</dna> function following <protein>interleukin-6</protein> stimulation , a treatment that leads to increases in C/EBP activation ."}
{"id": "2801", "text": "Thus , HIV-1 LTR ATF/CREB binding site sequence variation may modulate cellular signaling at the viral promoter through the C/EBP pathway", "annotated_text": "Thus , <dna>HIV-1 LTR</dna> <dna>ATF/CREB binding site</dna> sequence variation may modulate cellular signaling at the <dna>viral promoter</dna> through the C/EBP pathway"}
{"id": "2802", "text": "Selective inhibition of interleukin-4 gene expression in human T cells by aspirin .", "annotated_text": "Selective inhibition of interleukin-4 gene expression in <cell_type>human T cells</cell_type> by aspirin ."}
{"id": "2803", "text": "Previous studies indicated that aspirin ( acetylsalicylic acid [ ASA ] ) can have profound immunomodulatory effects by regulating cytokine gene expression in several types of cells .", "annotated_text": "Previous studies indicated that aspirin ( acetylsalicylic acid [ ASA ] ) can have profound immunomodulatory effects by regulating cytokine gene expression in several types of cells ."}
{"id": "2804", "text": "This study is the first in which concentrations of ASA in the therapeutic range were found to significantly reduce interleukin ( IL ) -4 secretion and RNA expression in freshly isolated and mitogen-primed human CD4+ T cells .", "annotated_text": "This study is the first in which concentrations of ASA in the therapeutic range were found to significantly reduce <protein>interleukin ( IL ) -4</protein> secretion and RNA expression in <cell_type>freshly isolated and mitogen-primed human CD4+ T cells</cell_type> ."}
{"id": "2805", "text": "In contrast , ASA did not affect IL-13 , interferon-gamma , and IL-2 expression .", "annotated_text": "In contrast , ASA did not affect <protein>IL-13</protein> , <protein>interferon-gamma</protein> , and <protein>IL-2</protein> expression ."}
{"id": "2806", "text": "ASA inhibited IL-4 , but not IL-2 , promoter-driven chloramphenicol acetyltransferase expression in transiently transfected Jurkat T cells .", "annotated_text": "ASA inhibited <protein>IL-4</protein> , but not <protein>IL-2</protein> , promoter-driven chloramphenicol acetyltransferase expression in transiently transfected <cell_line>Jurkat T cells</cell_line> ."}
{"id": "2807", "text": "The structurally unrelated nonsteroidal anti-inflammatory drugs indomethacin and flurbiprofen did not affect cytokine gene expression in T cells , whereas the weak cyclo-oxygenase inhibitor salicylic acid was at least as effective as ASA in inhibiting IL-4 expression and promoter activity .", "annotated_text": "The structurally unrelated nonsteroidal anti-inflammatory drugs indomethacin and flurbiprofen did not affect cytokine gene expression in <cell_type>T cells</cell_type> , whereas the weak cyclo-oxygenase inhibitor salicylic acid was at least as effective as ASA in inhibiting <protein>IL-4</protein> expression and promoter activity ."}
{"id": "2808", "text": "The inhibitory effect of ASA on IL-4 transcription was not mediated by decreased nuclear expression of the known salicylate target nuclear factor ( NF ) -kappaB and was accompanied by reduced binding of an inducible factor to an IL-4 promoter region upstream of , but not overlapping , the NF of activated T cells- and NF-kappaB-binding P1 element .", "annotated_text": "The inhibitory effect of ASA on IL-4 transcription was not mediated by decreased nuclear expression of the known <protein>salicylate target nuclear factor ( NF ) -kappaB</protein> and was accompanied by reduced binding of an inducible factor to an <dna>IL-4 promoter region</dna> upstream of , but not overlapping , the <dna>NF of activated T cells- and NF-kappaB-binding P1 element</dna> ."}
{"id": "2809", "text": "It is concluded that anti-inflammatory salicylates , by means of a previously unrecognized mechanism of action , can influence the nature of adaptive immune responses by selectively inhibiting the expression of IL-4 , a critical effector of these responses , in CD4+ T cells .", "annotated_text": "It is concluded that anti-inflammatory salicylates , by means of a previously unrecognized mechanism of action , can influence the nature of adaptive immune responses by selectively inhibiting the expression of <protein>IL-4</protein> , a critical effector of these responses , in <cell_type>CD4+ T cells</cell_type> ."}
{"id": "2810", "text": "Molecular and cellular mediators of interleukin-1 -dependent acute inflammatory arthritis .", "annotated_text": "Molecular and cellular mediators of <protein>interleukin-1</protein> -dependent acute inflammatory arthritis ."}
{"id": "2811", "text": "OBJECTIVE : To examine the molecular and cellular mechanisms in a model of acute inflammatory monarticular arthritis induced by methylated bovine serum albumin ( mBSA ) and interleukin-1 ( IL-1 ) .", "annotated_text": "OBJECTIVE : To examine the molecular and cellular mechanisms in a model of acute inflammatory monarticular arthritis induced by <protein>methylated bovine serum albumin</protein> ( <protein>mBSA</protein> ) and <protein>interleukin-1</protein> ( <protein>IL-1</protein> ) ."}
{"id": "2812", "text": "METHODS : Mice were injected intraarticularly with mBSA on day 0 and subcutaneously with recombinant human IL-1beta on days 0-2 .", "annotated_text": "METHODS : Mice were injected intraarticularly with <protein>mBSA</protein> on day 0 and subcutaneously with <protein>recombinant human IL-1beta</protein> on days 0-2 ."}
{"id": "2813", "text": "At day 7 , knee joints were removed and assessed histologically .", "annotated_text": "At day 7 , knee joints were removed and assessed histologically ."}
{"id": "2814", "text": "Flow cytometry and RNase protection were used to analyze IL-1 -dependent events .", "annotated_text": "Flow cytometry and RNase protection were used to analyze <protein>IL-1</protein> -dependent events ."}
{"id": "2815", "text": "RESULTS : C57BL/6 ( B6 ) , 129/Sv , and ( B6 x 129/ Sv ) F1 hybrid mice , all H-2b strains , were susceptible to mBSA /IL-1-induced arthritis , whereas C3H/HeJ ( H-2k ) mice were not .", "annotated_text": "RESULTS : C57BL/6 ( B6 ) , 129/Sv , and ( B6 x 129/ Sv ) F1 hybrid mice , all H-2b strains , were susceptible to <protein>mBSA</protein> /IL-1-induced arthritis , whereas C3H/HeJ ( H-2k ) mice were not ."}
{"id": "2816", "text": "B6 mice lacking T and B cells ( RAG1-/- ) or major histocompatibility complex ( MHC ) class II antigens ( MHCII-/- ) , and B6 mice treated with a CD4+ T cell-depleting monoclonal antibody , were resistant to disease .", "annotated_text": "B6 mice lacking <cell_type>T and B cells</cell_type> ( RAG1-/- ) or <protein>major histocompatibility complex ( MHC ) class II antigens</protein> ( MHCII-/- ) , and B6 mice treated with a <protein>CD4+ T cell-depleting monoclonal antibody</protein> , were resistant to disease ."}
{"id": "2817", "text": "In contrast , B cell-deficient ( muMT/ muMT ) mice developed arthritis at an incidence and severity similar to that of controls .", "annotated_text": "In contrast , B cell-deficient ( muMT/ muMT ) mice developed arthritis at an incidence and severity similar to that of controls ."}
{"id": "2818", "text": "RelB-deficient ( RelB-/- ) bone marrow chimeric mice had arthritis that was significantly reduced in incidence and severity .", "annotated_text": "RelB-deficient ( RelB-/- ) bone marrow chimeric mice had arthritis that was significantly reduced in incidence and severity ."}
{"id": "2819", "text": "In B6 mice , flow cytometry demonstrated an IL-1-dependent leukocyte infiltration into the synovial compartment and RNase protection assays revealed induction of messenger RNA ( mRNA ) for the chemokines monocyte chemoattractant protein 1 , macrophage inhibitory protein 2 ( MIP-2 ) , RANTES , MIP-1alpha , and MIP-1beta , in vivo and in vitro .", "annotated_text": "In B6 mice , flow cytometry demonstrated an <cell_type>IL-1-dependent leukocyte</cell_type> infiltration into the synovial compartment and RNase protection assays revealed induction of <rna>messenger RNA</rna> ( <rna>mRNA</rna> ) for the <protein>chemokines</protein> <protein>monocyte chemoattractant protein 1</protein> , <protein>macrophage inhibitory protein 2</protein> ( <protein>MIP-2</protein> ) , <protein>RANTES</protein> , <protein>MIP-1alpha</protein> , and <protein>MIP-1beta</protein> , in vivo and in vitro ."}
{"id": "2820", "text": "CONCLUSION : Arthritis induced by mBSA / IL-1 is strain specific and dependent on CD4+ T lymphocytes and at least partially on RelB , but not on B lymphocytes or antibody .", "annotated_text": "CONCLUSION : Arthritis induced by <protein>mBSA</protein> / <protein>IL-1</protein> is strain specific and dependent on <cell_type>CD4+ T lymphocytes</cell_type> and at least partially on <protein>RelB</protein> , but not on <cell_type>B lymphocytes</cell_type> or <protein>antibody</protein> ."}
{"id": "2821", "text": "IL-1 contributes to leukocyte recruitment to the synovium and directly induces chemokine mRNA production by synovial cells .", "annotated_text": "<protein>IL-1</protein> contributes to leukocyte recruitment to the synovium and directly induces chemokine mRNA production by <cell_type>synovial cells</cell_type> ."}
{"id": "2822", "text": "This model of acute monarticular arthritis is particularly suitable for further investigations into cell-mediated immunity in arthritis and the role of IL-1 .", "annotated_text": "This model of acute monarticular arthritis is particularly suitable for further investigations into cell-mediated immunity in arthritis and the role of <protein>IL-1</protein> ."}
{"id": "2823", "text": "Positive and negative regulation of granulopoiesis by endogenous RARalpha .", "annotated_text": "Positive and negative regulation of granulopoiesis by <protein>endogenous RARalpha</protein> ."}
{"id": "2824", "text": "Acute promyelocytic leukemia ( APL ) is always associated with chromosomal translocations that disrupt the retinoic acid receptor alpha ( RARalpha ) gene .", "annotated_text": "Acute promyelocytic leukemia ( APL ) is always associated with chromosomal translocations that disrupt the <dna>retinoic acid receptor alpha ( RARalpha ) gene</dna> ."}
{"id": "2825", "text": "Whether these translocations relate to a role for endogenous RARalpha in normal granulopoiesis remains uncertain because most studies addressing this question have used non-physiological overexpression systems .", "annotated_text": "Whether these translocations relate to a role for <protein>endogenous RARalpha</protein> in normal granulopoiesis remains uncertain because most studies addressing this question have used non-physiological overexpression systems ."}
{"id": "2826", "text": "Granulocyte differentiation in cells derived from RARalpha-deficient ( RARalpha ( -/- ) ) mice was studied and evaluated in the context of agonist-bound and ligand-free RARalpha .", "annotated_text": "Granulocyte differentiation in cells derived from RARalpha-deficient ( RARalpha ( -/- ) ) mice was studied and evaluated in the context of <protein>agonist-bound and ligand-free RARalpha</protein> ."}
{"id": "2827", "text": "Our results demonstrate that RARalpha is dispensable for granulopoiesis , as RARalpha ( -/- ) mice have a normal granulocyte population despite an impaired ability to respond to retinoids .", "annotated_text": "Our results demonstrate that <protein>RARalpha</protein> is dispensable for granulopoiesis , as RARalpha ( -/- ) mice have a <cell_type>normal granulocyte population</cell_type> despite an impaired ability to respond to retinoids ."}
{"id": "2828", "text": "However , although it is not absolutely required , RARalpha can bidirectionally modulate granulopoiesis .", "annotated_text": "However , although it is not absolutely required , <protein>RARalpha</protein> can bidirectionally modulate granulopoiesis ."}
{"id": "2829", "text": "RARalpha stimulates differentiation in response to exogenous retinoic acid .", "annotated_text": "<protein>RARalpha</protein> stimulates differentiation in response to exogenous retinoic acid ."}
{"id": "2830", "text": "Furthermore , endogenous retinoids control granulopoiesis in vivo , as either vitamin A-deficient mice or animals treated with an RAR antagonist accumulate more immature granulocytes in their bone marrow .", "annotated_text": "Furthermore , endogenous retinoids control granulopoiesis in vivo , as either vitamin A-deficient mice or animals treated with an RAR antagonist accumulate more <cell_type>immature granulocytes</cell_type> in their bone marrow ."}
{"id": "2831", "text": "Conversely , RARalpha acts to limit differentiation in the absence of ligand because granulocyte precursors from RARalpha ( -/- ) mice differentiate earlier in culture .", "annotated_text": "Conversely , <protein>RARalpha</protein> acts to limit differentiation in the absence of <protein>ligand</protein> because <cell_type>granulocyte precursors</cell_type> from RARalpha ( -/- ) mice differentiate earlier in culture ."}
{"id": "2832", "text": "Thus , the block in granulopoiesis exerted by RARalpha fusion proteins expressed in APL cells may correspond to an amplification of a normal function of unliganded RARalpha .", "annotated_text": "Thus , the block in granulopoiesis exerted by <protein>RARalpha</protein> <protein>fusion proteins</protein> expressed in <cell_type>APL cells</cell_type> may correspond to an amplification of a normal function of <protein>unliganded RARalpha</protein> ."}
{"id": "2833", "text": "Expression and function of a stem cell promoter for the murine CBFalpha2 gene : distinct roles and regulation in natural killer and T cell development .", "annotated_text": "Expression and function of a <dna>stem cell promoter</dna> for the <dna>murine CBFalpha2 gene</dna> : distinct roles and regulation in <cell_type>natural killer and T cell</cell_type> development ."}
{"id": "2834", "text": "The Runt family transcription factor CBFalpha2 ( AML1 , PEBP2alphaB , or Runx1 ) is required by hematopoietic stem cells and expressed at high levels in T-lineage cells .", "annotated_text": "The <protein>Runt family transcription factor</protein> <protein>CBFalpha2</protein> ( <protein>AML1</protein> , <protein>PEBP2alphaB</protein> , or <protein>Runx1</protein> ) is required by <cell_type>hematopoietic stem cells</cell_type> and expressed at high levels in <cell_type>T-lineage cells</cell_type> ."}
{"id": "2835", "text": "In human T cells CBFalpha2 is usually transcribed from a different promoter ( distal promoter ) than in myeloid cells ( proximal promoter ) , but the developmental and functional significance of this promoter switch has not been known .", "annotated_text": "In <cell_type>human T cells</cell_type> <protein>CBFalpha2</protein> is usually transcribed from a <dna>different promoter</dna> ( <dna>distal promoter</dna> ) than in <cell_type>myeloid cells</cell_type> ( <dna>proximal promoter</dna> ) , but the developmental and functional significance of this promoter switch has not been known ."}
{"id": "2836", "text": "Here , we report that both coding and noncoding sequences of the distal 5 ' end are highly conserved between the human and the murine genes , and the distal promoter is responsible for the overwhelming majority of CBFalpha2 expression in murine hematopoietic stem cells as well as in T cells .", "annotated_text": "Here , we report that both <dna>coding and noncoding sequences</dna> of the <dna>distal 5 ' end</dna> are highly conserved between the <dna>human and the murine genes</dna> , and the <dna>distal promoter</dna> is responsible for the overwhelming majority of CBFalpha2 expression in murine <cell_type>hematopoietic stem cells</cell_type> as well as in <cell_type>T cells</cell_type> ."}
{"id": "2837", "text": "Distal promoter activity is maintained throughout T cell development and at lower levels in B cell development , but downregulated in natural killer cell development .", "annotated_text": "Distal promoter activity is maintained throughout T cell development and at lower levels in B cell development , but downregulated in natural killer cell development ."}
{"id": "2838", "text": "The distal N-terminal isoform binds to functionally important regulatory sites from known target genes with two- to threefold higher affinity than the proximal N-terminal isoform .", "annotated_text": "The <dna>distal N-terminal isoform</dna> binds to functionally important <dna>regulatory sites</dna> from known <dna>target genes</dna> with two- to threefold higher affinity than the <dna>proximal N-terminal isoform</dna> ."}
{"id": "2839", "text": "Neither full-length isoform alters growth of a myeloid cell line under nondifferentiating conditions , but the proximal isoform selectively delays mitotic arrest of the cell line under differentiating conditions , resulting in the generation of greater numbers of neutrophils .", "annotated_text": "Neither <dna>full-length isoform</dna> alters growth of a <cell_line>myeloid cell line</cell_line> under nondifferentiating conditions , but the <dna>proximal isoform</dna> selectively delays mitotic arrest of the cell line under differentiating conditions , resulting in the generation of greater numbers of <cell_type>neutrophils</cell_type> ."}
{"id": "2840", "text": "Constitutive PI3-K activity is essential for proliferation , but not survival , of Theileria parva-transformed B cells .", "annotated_text": "Constitutive PI3-K activity is essential for proliferation , but not survival , of <cell_type>Theileria parva-transformed B cells</cell_type> ."}
{"id": "2841", "text": "Theileria is an intracellular parasite that causes lymphoproliferative disorders in cattle , and infection of leucocytes induces a transformed phenotype similar to tumour cells , but the mechanisms by which the parasite induces this phenotype are not understood .", "annotated_text": "Theileria is an intracellular parasite that causes lymphoproliferative disorders in cattle , and infection of <cell_type>leucocytes</cell_type> induces a transformed phenotype similar to <cell_type>tumour cells</cell_type> , but the mechanisms by which the parasite induces this phenotype are not understood ."}
{"id": "2842", "text": "Here , we show that infected B lymphocytes display constitutive phosphoinositide 3-kinase ( PI3-K ) activity , which appears to be necessary for proliferation , but not survival .", "annotated_text": "Here , we show that <cell_type>infected B lymphocytes</cell_type> display constitutive phosphoinositide 3-kinase ( PI3-K ) activity , which appears to be necessary for proliferation , but not survival ."}
{"id": "2843", "text": "Importantly , we demonstrate that one mechanism by which PI3-K mediates the proliferation of infected B lymphocytes is through the induction of a granulocyte-monocyte colony-stimulating factor ( GM-CSF ) -dependent autocrine loop .", "annotated_text": "Importantly , we demonstrate that one mechanism by which <protein>PI3-K</protein> mediates the proliferation of <cell_type>infected B lymphocytes</cell_type> is through the induction of a <protein>granulocyte-monocyte colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) -dependent autocrine loop ."}
{"id": "2844", "text": "PI3-K induction of GM-CSF appears to be at the transcriptional level and , consistently , we demonstrate that PI3-K is also involved in the constitutive induction of AP-1 and NF-kappaB , which characterizes Theileria-infected leucocytes .", "annotated_text": "<protein>PI3-K</protein> induction of <protein>GM-CSF</protein> appears to be at the transcriptional level and , consistently , we demonstrate that <protein>PI3-K</protein> is also involved in the constitutive induction of <protein>AP-1</protein> and <protein>NF-kappaB</protein> , which characterizes Theileria-infected <cell_type>leucocytes</cell_type> ."}
{"id": "2845", "text": "Taken together , our results highlight a novel strategy exploited by the intracellular parasite Theileria to induce continued proliferation of its host leucocyte .", "annotated_text": "Taken together , our results highlight a novel strategy exploited by the intracellular parasite Theileria to induce continued proliferation of its <cell_type>host leucocyte</cell_type> ."}
{"id": "2846", "text": "Lymphokine dependence of STAT3 activation produced by surface immunoglobulin cross-linking and by phorbol ester plus calcium ionophore treatment in B cells .", "annotated_text": "<protein>Lymphokine</protein> dependence of STAT3 activation produced by surface immunoglobulin cross-linking and by phorbol ester plus calcium ionophore treatment in <cell_type>B cells</cell_type> ."}
{"id": "2847", "text": "Stimulation of B cells by surface immunoglobulin ( sIg ) triggering , or through the mitogenic combination of phorbol ester and calcium ionophore , is accompanied by activation of STAT transcription factors .", "annotated_text": "Stimulation of <cell_type>B cells</cell_type> by <protein>surface immunoglobulin</protein> ( <protein>sIg</protein> ) triggering , or through the mitogenic combination of phorbol ester and calcium ionophore , is accompanied by activation of <protein>STAT transcription factors</protein> ."}
{"id": "2848", "text": "The mechanism responsible for the delayed nuclear accumulation of phosphorylated STAT3 was examined in detail , focusing on the role of B cell-derived lymphokines .", "annotated_text": "The mechanism responsible for the delayed nuclear accumulation of <protein>phosphorylated STAT3</protein> was examined in detail , focusing on the role of <protein>B cell-derived lymphokines</protein> ."}
{"id": "2849", "text": "sIg -induced activation of STAT3 was partially inhibited in B cells obtained from IL-6- or IL-10-deficient mice , and was partially blocked by neutralizing antibodies directed against either of these lymphokines .", "annotated_text": "<protein>sIg</protein> -induced activation of <protein>STAT3</protein> was partially inhibited in <cell_type>B cells</cell_type> obtained from IL-6- or IL-10-deficient mice , and was partially blocked by <protein>neutralizing antibodies</protein> directed against either of these <protein>lymphokines</protein> ."}
{"id": "2850", "text": "sIg -induced STAT3 activation was completely inhibited by combining IL-6- and IL-10-specific neutralizing antibodies , or by adding individual neutralizing antibodies to B cells obtained from lymphokine-deficient animals .", "annotated_text": "<protein>sIg</protein> -induced STAT3 activation was completely inhibited by combining <protein>IL-6- and IL-10-specific neutralizing antibodies</protein> , or by adding individual <protein>neutralizing antibodies</protein> to <cell_type>B cells</cell_type> obtained from lymphokine-deficient animals ."}
{"id": "2851", "text": "In contrast , IL-10 alone appeared to account for STAT3 activation resulting from B cell stimulation with phorbol ester and calcium ionophore .", "annotated_text": "In contrast , <protein>IL-10</protein> alone appeared to account for STAT3 activation resulting from B cell stimulation with phorbol ester and calcium ionophore ."}
{"id": "2852", "text": "In keeping with these results , soluble IL-6 and IL-10 were found in supernatant fluid obtained from stimulated B cells .", "annotated_text": "In keeping with these results , soluble <protein>IL-6</protein> and <protein>IL-10</protein> were found in supernatant fluid obtained from <cell_type>stimulated B cells</cell_type> ."}
{"id": "2853", "text": "This work indicates that a lymphokine pathway is responsible for STAT3 activation that occurs late after B cell stimulation , and points out differences in B cell activation that result from stimulation through the antigen receptor and through pharmacological mimicry of signaling mediators .", "annotated_text": "This work indicates that a lymphokine pathway is responsible for STAT3 activation that occurs late after B cell stimulation , and points out differences in B cell activation that result from stimulation through the <protein>antigen receptor</protein> and through pharmacological mimicry of <protein>signaling mediators</protein> ."}
{"id": "2854", "text": "Transcription factor AP-4 is a ligand for immunoglobulin-kappa promoter E-box elements .", "annotated_text": "<protein>Transcription factor AP-4</protein> is a <protein>ligand</protein> for <dna>immunoglobulin-kappa promoter E-box elements</dna> ."}
{"id": "2855", "text": "Immunoglobulin ( Ig ) -kappa promoters from humans and mice share conserved sequences .", "annotated_text": "<dna>Immunoglobulin ( Ig ) -kappa promoters</dna> from humans and mice share <dna>conserved sequences</dna> ."}
{"id": "2856", "text": "The octamer element is common to all Ig promoters and pivotal for their function .", "annotated_text": "The <dna>octamer element</dna> is common to all <dna>Ig promoters</dna> and pivotal for their function ."}
{"id": "2857", "text": "However , other conserved sequence motifs , that differ between Ig variable gene families , are required for normal promoter function .", "annotated_text": "However , other <dna>conserved sequence motifs</dna> , that differ between <dna>Ig variable gene families</dna> , are required for normal promoter function ."}
{"id": "2858", "text": "These conserved motifs do not stimulate transcription in the absence of an octamer .", "annotated_text": "These conserved motifs do not stimulate transcription in the absence of an <dna>octamer</dna> ."}
{"id": "2859", "text": "One example is an E-box of the E47/E12 type ( 5'-CAGCTG-3 ' ) , which is found in all promoters of the human and murine Ig-kappa gene subgroups/families , with the exception of subgroups II and VI and their related murine families .", "annotated_text": "One example is an <dna>E-box</dna> of the <dna>E47/E12 type ( 5'-CAGCTG-3 ' )</dna> , which is found in all promoters of the <dna>human and murine Ig-kappa gene subgroups/families</dna> , with the exception of subgroups II and VI and their related <dna>murine families</dna> ."}
{"id": "2860", "text": "In the present study we show that the ubiquitously expressed transcription factor AP-4 , and not E47 , interacts specifically with the kappa promoter E-boxes when tested in electrophoretic mobility-shift assays using nuclear extracts derived from human and murine B-cell lines .", "annotated_text": "In the present study we show that the ubiquitously expressed <protein>transcription factor AP-4</protein> , and not <protein>E47</protein> , interacts specifically with the <dna>kappa promoter E-boxes</dna> when tested in electrophoretic mobility-shift assays using nuclear extracts derived from <cell_line>human and murine B-cell lines</cell_line> ."}
{"id": "2861", "text": "Furthermore , AP-4 , unlike E47 , did not act as a transactivator , which is in agreement with previous studies on intact kappa promoters , showing that transcription is absent when the octamer element has been mutated .", "annotated_text": "Furthermore , <protein>AP-4</protein> , unlike <protein>E47</protein> , did not act as a <protein>transactivator</protein> , which is in agreement with previous studies on intact <dna>kappa promoters</dna> , showing that transcription is absent when the <dna>octamer element</dna> has been mutated ."}
{"id": "2862", "text": "Based on these data , and the conservation of the 5'-CAGCTG-3 ' motif among human and murine kappa promoters , we propose that AP-4 is the major ligand for Ig-kappa promoter E-boxes .", "annotated_text": "Based on these data , and the conservation of the <dna>5'-CAGCTG-3 ' motif</dna> among <dna>human and murine kappa promoters</dna> , we propose that <protein>AP-4</protein> is the <protein>major ligand</protein> for <dna>Ig-kappa promoter E-boxes</dna> ."}
{"id": "2863", "text": "A 16-mer peptide ( RQIKIWFQNRRMKWKK ) from antennapedia preferentially targets the Class I pathway .", "annotated_text": "A 16-mer peptide ( RQIKIWFQNRRMKWKK ) from antennapedia preferentially targets the Class I pathway ."}
{"id": "2864", "text": "Translocation of antigenic peptides into the cytosol of antigen presenting cells facilitates proteosomal processing and loading into Class I molecules for MHC presentation on the cell surface .", "annotated_text": "Translocation of antigenic peptides into the cytosol of <cell_type>antigen presenting cells</cell_type> facilitates proteosomal processing and loading into <protein>Class I molecules</protein> for MHC presentation on the cell surface ."}
{"id": "2865", "text": "The DNA binding domain of the Drosophila transcription factor ( Antennapedia ) , a 60 amino acid protein , is rapidly taken up by cells and has been fused to selected antigens to enhance their immunogenicity .", "annotated_text": "The <protein>DNA binding domain</protein> of the <protein>Drosophila transcription factor</protein> ( <protein>Antennapedia</protein> ) , a <protein>60 amino acid protein</protein> , is rapidly taken up by cells and has been fused to selected <protein>antigens</protein> to enhance their immunogenicity ."}
{"id": "2866", "text": "We now demonstrate that a 16 amino acid peptide from antennapedia can facilitate the cytoplasmic uptake of CTL epitope 9-mer peptides .", "annotated_text": "We now demonstrate that a 16 amino acid peptide from antennapedia can facilitate the cytoplasmic uptake of CTL epitope 9-mer peptides ."}
{"id": "2867", "text": "Synthetic peptides were made containing the 16-mer antennapedia peptide linked in tandem to the ovalbumin SIINFEKL CTL peptide .", "annotated_text": "Synthetic peptides were made containing the 16-mer antennapedia peptide linked in tandem to the ovalbumin SIINFEKL CTL peptide ."}
{"id": "2868", "text": "The peptide complex was shown to rapidly internalise into APCs by confocal microscopy .", "annotated_text": "The peptide complex was shown to rapidly internalise into <cell_type>APCs</cell_type> by confocal microscopy ."}
{"id": "2869", "text": "This peptide induced CTL in C57BL/6 mice and protected them against growth of an ovalbumin expressing tumour cell line ( E.G7-OVA ) .", "annotated_text": "This peptide induced <cell_type>CTL</cell_type> in C57BL/6 mice and protected them against growth of an <cell_line>ovalbumin expressing tumour cell line</cell_line> ( <cell_line>E.G7-OVA</cell_line> ) ."}
{"id": "2870", "text": "The ability of the hybrid peptide to be processed and presented by APCs was similar , whether the SIINFEKL sequence was appended at the C-terminus or N-terminus of the Antennapedia peptide .", "annotated_text": "The ability of the hybrid peptide to be processed and presented by <cell_type>APCs</cell_type> was similar , whether the SIINFEKL sequence was appended at the <protein>C-terminus</protein> or <protein>N-terminus</protein> of the Antennapedia peptide ."}
{"id": "2871", "text": "The production of synthetic peptides containing other CTL peptide epitopes may be useful for priming CTLs in vitro and in vivo", "annotated_text": "The production of synthetic peptides containing other CTL peptide epitopes may be useful for priming <cell_type>CTLs</cell_type> in vitro and in vivo"}
{"id": "2872", "text": "Bone marrow cells promote TH2 polarization and inhibit virus-specific CTL generation .", "annotated_text": "<cell_type>Bone marrow cells</cell_type> promote TH2 polarization and inhibit virus-specific CTL generation ."}
{"id": "2873", "text": "This laboratory recently reported that human bone marrow cells ( BMC ) inhibit the generation of virus-specific CTL in culture .", "annotated_text": "This laboratory recently reported that <cell_type>human bone marrow cells</cell_type> ( <cell_type>BMC</cell_type> ) inhibit the generation of <cell_type>virus-specific CTL</cell_type> in culture ."}
{"id": "2874", "text": "The culture supernatants contained increased levels of prostaglandin E ( 2 ) ( PGE ( 2 ) ) ( shown to favor TH2 cell development ) and also inhibited EBV-CTL effector cell development .", "annotated_text": "The culture supernatants contained increased levels of <protein>prostaglandin E ( 2 ) ( PGE ( 2 ) )</protein> ( shown to favor TH2 cell development ) and also inhibited EBV-CTL effector cell development ."}
{"id": "2875", "text": "In this study , we obtained PBL from Epstein-Barr virus ( EBV ) IgG antibody positive kidney transplant recipients ( R ) and their living-related donors ( LRD ) one year after renal transplantation .", "annotated_text": "In this study , we obtained <cell_type>PBL</cell_type> from Epstein-Barr virus ( EBV ) <protein>IgG antibody</protein> positive kidney transplant recipients ( R ) and their living-related donors ( LRD ) one year after renal transplantation ."}
{"id": "2876", "text": "EBV-specific CTL were then generated in vitro by stimulating PBL with autologous EBV-transformed B cells ( EBV-B ) in the presence or absence of autologous BMC .", "annotated_text": "<cell_type>EBV-specific CTL</cell_type> were then generated in vitro by stimulating <cell_type>PBL</cell_type> with autologous <cell_type>EBV-transformed B cells</cell_type> ( <cell_type>EBV-B</cell_type> ) in the presence or absence of <cell_type>autologous BMC</cell_type> ."}
{"id": "2877", "text": "The addition of BMC to the EBV-CTL generation cultures increased the intracellular expression in CD3+ cells of IL-4 , -5 , -6 , -10 , and -13 .", "annotated_text": "The addition of <cell_type>BMC</cell_type> to the <cell_type>EBV-CTL generation cultures</cell_type> increased the intracellular expression in <cell_type>CD3+ cells</cell_type> of <protein>IL-4 , -5 , -6 , -10 , and -13</protein> ."}
{"id": "2878", "text": "These CD3+ cells also expressed increased levels of the TH2 associated receptor CCR3 .", "annotated_text": "These <cell_type>CD3+ cells</cell_type> also expressed increased levels of the <protein>TH2 associated receptor CCR3</protein> ."}
{"id": "2879", "text": "Inhibition was even observed by preparing EBV-CTL generating cultures in trans-wells that separated the autologous BMC from the PBL + EBV-B .", "annotated_text": "Inhibition was even observed by preparing <cell_type>EBV-CTL generating cultures</cell_type> in trans-wells that separated the <cell_type>autologous BMC</cell_type> from the <cell_type>PBL</cell_type> + <cell_type>EBV-B</cell_type> ."}
{"id": "2880", "text": "It was then observed that CD3+ cells obtained after 7 days of culture in the presence of autologous BMC could be used as inhibitors of EBV-CTL generation .", "annotated_text": "It was then observed that <cell_type>CD3+ cells</cell_type> obtained after 7 days of culture in the presence of <cell_type>autologous BMC</cell_type> could be used as inhibitors of EBV-CTL generation ."}
{"id": "2881", "text": "Protein Kinase A ( PKA ) , a cAMP kinase that is involved in the upregulation of TH2 cytokine activity , was increased in EBV-CTL cultures by the presence of BMC .", "annotated_text": "<protein>Protein Kinase A</protein> ( <protein>PKA</protein> ) , a <protein>cAMP kinase</protein> that is involved in the upregulation of <protein>TH2 cytokine</protein> activity , was increased in <cell_type>EBV-CTL cultures</cell_type> by the presence of <cell_type>BMC</cell_type> ."}
{"id": "2882", "text": "Additionally , IL-4-mediated signal transduction and activation of transcription ( STAT-6 ) phosphorylation was slightly increased .", "annotated_text": "Additionally , IL-4-mediated signal transduction and activation of transcription ( <protein>STAT-6</protein> ) phosphorylation was slightly increased ."}
{"id": "2883", "text": "These results show that the BMC inhibition is mediated by soluble factors ( cytokines ) and that cell-cell contact in this autologous system is not required , so that BMC ( at least partially , via cytokine production ) promote TH2 polarization in culture .", "annotated_text": "These results show that the <cell_type>BMC</cell_type> inhibition is mediated by <protein>soluble factors</protein> ( <protein>cytokines</protein> ) and that cell-cell contact in this autologous system is not required , so that <cell_type>BMC</cell_type> ( at least partially , via cytokine production ) promote TH2 polarization in culture ."}
{"id": "2884", "text": "Moreover , TH2 cells induced by culturing with autologous BMC directly inhibit EBV-CTL generation , and TH2 associated PKA , CCR3 , and STAT-6 phosphorylation are enhanced by BMC .", "annotated_text": "Moreover , <cell_type>TH2 cells</cell_type> induced by culturing with <cell_type>autologous BMC</cell_type> directly inhibit EBV-CTL generation , and <protein>TH2</protein> associated <protein>PKA</protein> , <protein>CCR3</protein> , and <protein>STAT-6</protein> phosphorylation are enhanced by <cell_type>BMC</cell_type> ."}
{"id": "2885", "text": "Reduction in DNA binding activity of the transcription factor Pax-5a in B lymphocytes of aged mice .", "annotated_text": "Reduction in DNA binding activity of the <protein>transcription factor</protein> <protein>Pax-5a</protein> in <cell_type>B lymphocytes</cell_type> of aged mice ."}
{"id": "2886", "text": "Aging has been associated with intrinsic changes of the humoral immune response , which may lead to an increased occurrence of autoimmune disorders and pathogenic susceptibility .", "annotated_text": "Aging has been associated with intrinsic changes of the humoral immune response , which may lead to an increased occurrence of autoimmune disorders and pathogenic susceptibility ."}
{"id": "2887", "text": "The transcription factor Pax-5 is a key regulator of B cell development .", "annotated_text": "The <protein>transcription factor</protein> <protein>Pax-5</protein> is a key regulator of B cell development ."}
{"id": "2888", "text": "Pax-5a/B cell-specific activator protein and an alternatively spliced isoform , Pax-5d , may have opposing functions in transcriptional regulation due to the lack of a transactivation domain in Pax-5d .", "annotated_text": "<protein>Pax-5a/B cell-specific activator protein</protein> and an <protein>alternatively spliced isoform , Pax-5d</protein> , may have opposing functions in transcriptional regulation due to the lack of a <protein>transactivation domain</protein> in <protein>Pax-5d</protein> ."}
{"id": "2889", "text": "To study B cell -specific changes that occur during the aging process , we investigated expression patterns of Pax-5a and 5d in mature B cells of young and aged mice .", "annotated_text": "To study <cell_type>B cell</cell_type> -specific changes that occur during the aging process , we investigated expression patterns of <protein>Pax-5a and 5d</protein> in <cell_type>mature B cells</cell_type> of young and aged mice ."}
{"id": "2890", "text": "RNase protection assays showed a similar transcriptional pattern for both age groups that indicates that aging has no affect on transcription initiation or alternative splicing for either isoform .", "annotated_text": "RNase protection assays showed a similar transcriptional pattern for both age groups that indicates that aging has no affect on transcription initiation or alternative splicing for either <protein>isoform</protein> ."}
{"id": "2891", "text": "In contrast , a significant reduction in the DNA binding activity of Pax-5a but not Pax-5d protein was observed in aged B cells in vitro , while Western blot analyses showed that similar levels of Pax-5a and 5d proteins were present in both age groups .", "annotated_text": "In contrast , a significant reduction in the DNA binding activity of <protein>Pax-5a</protein> but not <protein>Pax-5d</protein> protein was observed in <cell_type>aged B cells</cell_type> in vitro , while Western blot analyses showed that similar levels of <protein>Pax-5a and 5d</protein> proteins were present in both age groups ."}
{"id": "2892", "text": "The observed decrease in Pax-5a binding activity correlated with changes in expression of two Pax-5 target genes in aged B cells .", "annotated_text": "The observed decrease in <protein>Pax-5a</protein> binding activity correlated with changes in expression of two <dna>Pax-5 target genes</dna> in <cell_type>aged B cells</cell_type> ."}
{"id": "2893", "text": "Expression of the Ig J chain and the secreted form of Ig mu , which are both known to be suppressed by Pax-5a in mature B cells , were increased in B cells of aged mice .", "annotated_text": "Expression of the <protein>Ig J chain</protein> and the secreted form of <protein>Ig mu</protein> , which are both known to be suppressed by <protein>Pax-5a</protein> in <cell_type>mature B cells</cell_type> , were increased in <cell_type>B cells</cell_type> of aged mice ."}
{"id": "2894", "text": "Together , our studies suggest that changes associated with the aging phenotype cause posttranslational modification ( s ) of Pax-5a but not Pax-5d , which may lead to an abnormal B cell phenotype in aged mice , associated with elevated levels of J chain , and secretion of IgM", "annotated_text": "Together , our studies suggest that changes associated with the aging phenotype cause posttranslational modification ( s ) of <protein>Pax-5a</protein> but not <protein>Pax-5d</protein> , which may lead to an abnormal B cell phenotype in aged mice , associated with elevated levels of <protein>J chain</protein> , and secretion of <protein>IgM</protein>"}
{"id": "2895", "text": "NF-kappa B/Rel participation in the lymphokine-dependent proliferation of T lymphoid cells .", "annotated_text": "<protein>NF-kappa B/Rel</protein> participation in the lymphokine-dependent proliferation of <cell_type>T lymphoid cells</cell_type> ."}
{"id": "2896", "text": "Proliferative responses of lymphoid cells to IL-2 and IL-4 depend on activation of the cells , but the mechanism ( s ) by which activation enhances cellular competence to respond to cytokines is not fully understood .", "annotated_text": "Proliferative responses of <cell_type>lymphoid cells</cell_type> to <protein>IL-2</protein> and <protein>IL-4</protein> depend on activation of the cells , but the mechanism ( s ) by which activation enhances cellular competence to respond to <protein>cytokines</protein> is not fully understood ."}
{"id": "2897", "text": "The NF-kappaB/Rel family represents one signal transduction pathway induced during such activation .", "annotated_text": "The <protein>NF-kappaB/Rel family</protein> represents one signal transduction pathway induced during such activation ."}
{"id": "2898", "text": "We show in this study that inhibition of NF-kappaB through the expression of an IkappaBalpha ( inhibitory protein that dissociates from NF-kappaB ) mutant refractory to signal-induced degradation ( IkappaBalpha ( DeltaN ) ) interfered with the acquisition of competence to proliferate in response to IL-4 as well as IL-2 .", "annotated_text": "We show in this study that inhibition of <protein>NF-kappaB</protein> through the expression of an <protein>IkappaBalpha</protein> ( <protein>inhibitory protein</protein> that dissociates from <protein>NF-kappaB</protein> ) mutant refractory to signal-induced degradation ( <protein>IkappaBalpha ( DeltaN )</protein> ) interfered with the acquisition of competence to proliferate in response to <protein>IL-4</protein> as well as <protein>IL-2</protein> ."}
{"id": "2899", "text": "Thymocytes and T cells from IkappaBalpha ( DeltaN ) transgenic mice expressed normal levels of IL-2R subunits .", "annotated_text": "<cell_type>Thymocytes</cell_type> and <cell_type>T cells</cell_type> from <protein>IkappaBalpha ( DeltaN )</protein> transgenic mice expressed normal levels of <protein>IL-2R subunits</protein> ."}
{"id": "2900", "text": "However , transgenic cells exhibited a dramatic defect in Stat5A activation treatment with IL-2 , and a similar defect was observed for IL-4 -induced Stat5 .", "annotated_text": "However , <cell_type>transgenic cells</cell_type> exhibited a dramatic defect in Stat5A activation treatment with <protein>IL-2</protein> , and a similar defect was observed for <protein>IL-4</protein> -induced <protein>Stat5</protein> ."}
{"id": "2901", "text": "In contrast , T lymphoid cells with inhibition of NF-kappaB showed normal insulin receptor substrate-2 phosphorylation and only a modest decrease in Stat6 activation and insulin receptor substrate-1 phosphorylation after IL-4 stimulation .", "annotated_text": "In contrast , <cell_type>T lymphoid cells</cell_type> with inhibition of <protein>NF-kappaB</protein> showed normal insulin receptor substrate-2 phosphorylation and only a modest decrease in Stat6 activation and insulin receptor substrate-1 phosphorylation after IL-4 stimulation ."}
{"id": "2902", "text": "These results indicate that the NF-kappaB/Rel/IkappaBalpha system can regulate cytokine receptor capacitation through effects on the induction of downstream signaling by the Stat transcription factor family .", "annotated_text": "These results indicate that the NF-kappaB/Rel/IkappaBalpha system can regulate <protein>cytokine receptor</protein> capacitation through effects on the induction of downstream signaling by the <protein>Stat transcription factor family</protein> ."}
{"id": "2903", "text": "BMS-189453 , a novel retinoid receptor antagonist , is a potent testicular toxin .", "annotated_text": "BMS-189453 , a novel retinoid receptor antagonist , is a potent testicular toxin ."}
{"id": "2904", "text": "BMS-189453 is a synthetic retinoid that acts as an antagonist at retinoic acid receptors alpha , beta , and gamma .", "annotated_text": "BMS-189453 is a synthetic retinoid that acts as an antagonist at <protein>retinoic acid receptors alpha , beta , and gamma</protein> ."}
{"id": "2905", "text": "In Sprague Dawley rats at daily oral doses of 15 , 60 , or 240 mg/kg for 1 month , BMS-189453 produced increases in leukocyte counts , alkaline phosphatase and alanine aminotransferase levels , and marked testicular degeneration and atrophy at all doses .", "annotated_text": "In Sprague Dawley rats at daily oral doses of 15 , 60 , or 240 mg/kg for 1 month , BMS-189453 produced increases in <cell_type>leukocyte</cell_type> counts , <protein>alkaline phosphatase</protein> and <protein>alanine aminotransferase</protein> levels , and marked testicular degeneration and atrophy at all doses ."}
{"id": "2906", "text": "Significant overt signs of toxicity and deaths occurred at 240 mg/kg , whereas body-weight and food-consumption decreases occurred at 60 and 240 mg/kg .", "annotated_text": "Significant overt signs of toxicity and deaths occurred at 240 mg/kg , whereas body-weight and food-consumption decreases occurred at 60 and 240 mg/kg ."}
{"id": "2907", "text": "When BMS-189453 was administered to male rats at daily doses ranging from 12.5 to 100 mg/kg for 1 week , only minimal testicular changes occurred at all doses , shortly after the dosing period .", "annotated_text": "When BMS-189453 was administered to male rats at daily doses ranging from 12.5 to 100 mg/kg for 1 week , only minimal testicular changes occurred at all doses , shortly after the dosing period ."}
{"id": "2908", "text": "However , after a 1-month drug-free observation period , marked testicular atrophy was evident at all doses .", "annotated_text": "However , after a 1-month drug-free observation period , marked testicular atrophy was evident at all doses ."}
{"id": "2909", "text": "BMS-189453 was then administered at doses of 2 , 10 , or 50 mg/kg to male rats for 1 , 3 , or 7 consecutive days .", "annotated_text": "BMS-189453 was then administered at doses of 2 , 10 , or 50 mg/kg to male rats for 1 , 3 , or 7 consecutive days ."}
{"id": "2910", "text": "Dose- and duration-dependent testicular toxicity that occurred after a 1-month observation period did not recover , and , in some cases , was more severe 4 months after the last dose .", "annotated_text": "Dose- and duration-dependent testicular toxicity that occurred after a 1-month observation period did not recover , and , in some cases , was more severe 4 months after the last dose ."}
{"id": "2911", "text": "In rabbits administered BMS-189453 at oral doses of 2 , 10 , or 50 mg/kg for 1 week , testicular degeneration and atrophy were evident in the high-dose group at 1 month following treatment .", "annotated_text": "In rabbits administered BMS-189453 at oral doses of 2 , 10 , or 50 mg/kg for 1 week , testicular degeneration and atrophy were evident in the high-dose group at 1 month following treatment ."}
{"id": "2912", "text": "These studies indicate that retinoid antagonists can selectively produce progressive and prolonged testicular toxicity after single or repeated oral doses that are otherwise well tolerated .", "annotated_text": "These studies indicate that retinoid antagonists can selectively produce progressive and prolonged testicular toxicity after single or repeated oral doses that are otherwise well tolerated ."}
{"id": "2913", "text": "Sequential involvement of NFAT and Egr transcription factors in FasL regulation .", "annotated_text": "Sequential involvement of <protein>NFAT</protein> and <protein>Egr</protein> <protein>transcription factors</protein> in FasL regulation ."}
{"id": "2914", "text": "The critical function of NFAT proteins in maintaining lymphoid homeostasis was revealed in mice lacking both NFATp and NFAT4 ( DKO ) .", "annotated_text": "The critical function of <protein>NFAT proteins</protein> in maintaining lymphoid homeostasis was revealed in mice lacking both <protein>NFATp</protein> and <protein>NFAT4</protein> ( DKO ) ."}
{"id": "2915", "text": "DKO mice exhibit increased lymphoproliferation , decreased activation-induced cell death , and impaired induction of FasL .", "annotated_text": "DKO mice exhibit increased lymphoproliferation , decreased activation-induced cell death , and impaired induction of <protein>FasL</protein> ."}
{"id": "2916", "text": "The transcription factors Egr2 and Egr3 are potent activators of FasL expression .", "annotated_text": "The <protein>transcription factors</protein> <protein>Egr2</protein> and <protein>Egr3</protein> are potent activators of FasL expression ."}
{"id": "2917", "text": "Here we find that Egr2 and Egr3 are NFAT target genes .", "annotated_text": "Here we find that <dna>Egr2</dna> and <dna>Egr3</dna> are <dna>NFAT target genes</dna> ."}
{"id": "2918", "text": "Activation of FasL occurs via the NFAT -dependent induction of Egr3 , as demonstrated by the ability of exogenously provided NFATp to restore Egr -dependent FasL promoter activity in DKO lymph node cells .", "annotated_text": "Activation of <protein>FasL</protein> occurs via the <protein>NFAT</protein> -dependent induction of <dna>Egr3</dna> , as demonstrated by the ability of exogenously provided <protein>NFATp</protein> to restore <protein>Egr</protein> -dependent FasL promoter activity in <cell_type>DKO lymph node cells</cell_type> ."}
{"id": "2919", "text": "Further , Egr3 expression is enriched in Th1 cells , suggesting a molecular basis for the known preferential expression of FasL in the Th1 versus Th2 subset .", "annotated_text": "Further , <dna>Egr3</dna> expression is enriched in <cell_type>Th1 cells</cell_type> , suggesting a molecular basis for the known preferential expression of <protein>FasL</protein> in the Th1 versus Th2 subset ."}
{"id": "2920", "text": "Mechanisms and clinical relevance of nongenomic glucocorticoid actions .", "annotated_text": "Mechanisms and clinical relevance of nongenomic glucocorticoid actions ."}
{"id": "2921", "text": "Glucocorticoids have profound anti-inflammatory and immunosuppressive actions when used therapeutically .", "annotated_text": "Glucocorticoids have profound anti-inflammatory and immunosuppressive actions when used therapeutically ."}
{"id": "2922", "text": "The therapeutic dose is quite variable and depends on the disease , but ranges from very low to extremely high .", "annotated_text": "The therapeutic dose is quite variable and depends on the disease , but ranges from very low to extremely high ."}
{"id": "2923", "text": "The rationale for the use of various dosage regimens for specific clinical indications is the existence of three distinct , therapeutically relevant effects : genomic , specific nongenomic and unspecific nongenomic .", "annotated_text": "The rationale for the use of various dosage regimens for specific clinical indications is the existence of three distinct , therapeutically relevant effects : genomic , specific nongenomic and unspecific nongenomic ."}
{"id": "2924", "text": "Genomic effects are mediated by cytosolic receptors that alter expression of specific genes .", "annotated_text": "Genomic effects are mediated by <protein>cytosolic receptors</protein> that alter expression of specific genes ."}
{"id": "2925", "text": "Specific nongenomic effects occur within a few minutes and are mediated by steroid-selective membrane receptors .", "annotated_text": "Specific nongenomic effects occur within a few minutes and are mediated by <protein>steroid-selective membrane receptors</protein> ."}
{"id": "2926", "text": "Unspecific nongenomic effects occur within seconds , but only at high glucocorticoid dosages , and seem to result from direct interactions with biological membranes .", "annotated_text": "Unspecific nongenomic effects occur within seconds , but only at high glucocorticoid dosages , and seem to result from direct interactions with biological membranes ."}
{"id": "2927", "text": "For unspecific nongenomic effects , methylprednisolone and other glucocorticoids have been shown to inhibit cation cycling across the plasma membrane , but to have little effect on protein synthesis .", "annotated_text": "For unspecific nongenomic effects , methylprednisolone and other glucocorticoids have been shown to inhibit cation cycling across the plasma membrane , but to have little effect on protein synthesis ."}
{"id": "2928", "text": "Thus , glucocorticoids could diminish or prevent the acute immune response by interfering with processes such as the rise in intracellular Ca2+ concentration .", "annotated_text": "Thus , glucocorticoids could diminish or prevent the acute immune response by interfering with processes such as the rise in intracellular Ca2+ concentration ."}
{"id": "2929", "text": "It is proposed that the additional therapeutic benefit of higher doses is obtained via these nongenomic effects .", "annotated_text": "It is proposed that the additional therapeutic benefit of higher doses is obtained via these nongenomic effects ."}
{"id": "2930", "text": "High glucose-induced intercellular adhesion molecule-1 ( ICAM-1 ) expression through an osmotic effect in rat mesangial cells is PKC-NF-kappa B-dependent .", "annotated_text": "High glucose-induced <protein>intercellular adhesion molecule-1</protein> ( <protein>ICAM-1</protein> ) expression through an osmotic effect in <cell_type>rat mesangial cells</cell_type> is PKC-NF-kappa B-dependent ."}
{"id": "2931", "text": "AIMS/HYPOTHESIS : Infiltration of mononuclear cells and glomerular enlargement accompanied by glomerular cell proliferation are very early characteristics of the pathophysiology of diabetes .", "annotated_text": "AIMS/HYPOTHESIS : Infiltration of <cell_type>mononuclear cells</cell_type> and glomerular enlargement accompanied by <cell_type>glomerular cell</cell_type> proliferation are very early characteristics of the pathophysiology of diabetes ."}
{"id": "2932", "text": "To clarify the mechanism of early diabetic nephropathy , we measured [ 3H ] -thymidine incorporation and cell numbers to show the influence of a high ambient glucose concentration and the osmotic effect on rat mesangial cell proliferation .", "annotated_text": "To clarify the mechanism of early diabetic nephropathy , we measured [ 3H ] -thymidine incorporation and cell numbers to show the influence of a high ambient glucose concentration and the osmotic effect on <cell_type>rat mesangial cell</cell_type> proliferation ."}
{"id": "2933", "text": "We also measured the effect of high glucose on the expression of intercellular adhesion molecule-1 and vascular adhesion molecule-1 by flow cytometry and semiquantitative RT-PCR in mesangial cells and the adhesion of leukocytes to mesangial cells .", "annotated_text": "We also measured the effect of high glucose on the expression of <protein>intercellular adhesion molecule-1</protein> and <protein>vascular adhesion molecule-1</protein> by flow cytometry and semiquantitative RT-PCR in <cell_type>mesangial cells</cell_type> and the adhesion of <cell_type>leukocytes</cell_type> to <cell_type>mesangial cells</cell_type> ."}
{"id": "2934", "text": "METHODS/RESULTS : Cells exposed to high D-glucose ( 30 mmol/l ) caused an increase in [ 3H ] -thymidine incorporation and cell numbers at 24 and 48 h and normalized at 72 h ( p < 0.05 ) , whereas these changes were not found in high mannitol ( 30 mmol/l ) , IL-1 beta , or TNF alpha -stimulated mesangial cells .", "annotated_text": "METHODS/RESULTS : Cells exposed to high D-glucose ( 30 mmol/l ) caused an increase in [ 3H ] -thymidine incorporation and cell numbers at 24 and 48 h and normalized at 72 h ( p < 0.05 ) , whereas these changes were not found in high mannitol ( 30 mmol/l ) , <protein>IL-1 beta</protein> , or <protein>TNF alpha</protein> -stimulated <cell_type>mesangial cells</cell_type> ."}
{"id": "2935", "text": "Cells exposed to high-glucose ( 15 , 30 , or 60 mmol/l ) or osmotic agents ( L-glucose , raffinose and mannitol ) showed that intercellular adhesion molecule-1 expression began to increase after 24 h , reached its maximum at 24 and 48 h and gradually decreased afterwards .", "annotated_text": "Cells exposed to high-glucose ( 15 , 30 , or 60 mmol/l ) or osmotic agents ( L-glucose , raffinose and mannitol ) showed that <protein>intercellular adhesion molecule-1</protein> expression began to increase after 24 h , reached its maximum at 24 and 48 h and gradually decreased afterwards ."}
{"id": "2936", "text": "The stimulatory effects of high glucose and high mannitol on mRNA expression were observed as early as 6 h and reached its maximum at 12 h .", "annotated_text": "The stimulatory effects of high glucose and high mannitol on mRNA expression were observed as early as 6 h and reached its maximum at 12 h ."}
{"id": "2937", "text": "Up-regulation of ICAM-1 protein and mRNA was also found in IL-1-beta and TNF-alpha -stimulated mesangial cells .", "annotated_text": "Up-regulation of <protein>ICAM-1</protein> protein and mRNA was also found in <protein>IL-1-beta</protein> and <protein>TNF-alpha</protein> -stimulated <cell_type>mesangial cells</cell_type> ."}
{"id": "2938", "text": "Neither vascular adhesion molecule-1 protein nor mRNA expression was , however , affected by high glucose and high mannitol .", "annotated_text": "Neither <protein>vascular adhesion molecule-1</protein> protein nor mRNA expression was , however , affected by high glucose and high mannitol ."}
{"id": "2939", "text": "Notably , the protein kinase C inhibitors calphostin C and staurosporine reduced high glucose- or high mannitol-induced intercellular adhesion molecule-1 mRNA expression and high glucose-induced proliferation .", "annotated_text": "Notably , the protein kinase C inhibitors calphostin C and staurosporine reduced high glucose- or high mannitol-induced <rna>intercellular adhesion molecule-1</rna> mRNA expression and high glucose-induced proliferation ."}
{"id": "2940", "text": "Furthermore , the NF-kappa B inhibitor N-tosyl-L-phenylalanine chloromethyl ketone reduced high glucose- or high mannitol-induced intercellular adhesion molecule-1 mRNA expression and high glucose-induced proliferation .", "annotated_text": "Furthermore , the NF-kappa B inhibitor N-tosyl-L-phenylalanine chloromethyl ketone reduced high glucose- or high mannitol-induced <rna>intercellular adhesion molecule-1</rna> mRNA expression and high glucose-induced proliferation ."}
{"id": "2941", "text": "Results showed that high glucose ( 15 , 30 mmol/l ) or high concentrations of osmotic agents remarkably increased the number of adherent leukocytes to mesangial cells ( p < 0.01 ) compared with control cells ( 5 mmol/l D-glucose ) .", "annotated_text": "Results showed that high glucose ( 15 , 30 mmol/l ) or high concentrations of osmotic agents remarkably increased the number of adherent <cell_type>leukocytes</cell_type> to <cell_type>mesangial cells</cell_type> ( p < 0.01 ) compared with <cell_type>control cells</cell_type> ( 5 mmol/l D-glucose ) ."}
{"id": "2942", "text": "Functional blocking of intercellular adhesion molecule-1 on mesangial cells with rat intercellular adhesion molecule-1 monoclonal antibody , calphostin C , staurosporine , or N-tosyl-L-phenylalanine chloromethyl ketone significantly inhibited high glucose- or high mannitol-induced increase in leukocyte adhesion ( p < < 0.05 ) .", "annotated_text": "Functional blocking of <protein>intercellular adhesion molecule-1</protein> on <cell_type>mesangial cells</cell_type> with <protein>rat intercellular adhesion molecule-1 monoclonal antibody</protein> , calphostin C , staurosporine , or N-tosyl-L-phenylalanine chloromethyl ketone significantly inhibited high glucose- or high mannitol-induced increase in leukocyte adhesion ( p < < 0.05 ) ."}
{"id": "2943", "text": "CONCLUSION/INTERPRETATION : These results suggest that high glucose can upregulate intercellular adhesion molecule-1 protein and mRNA expression but not vascular adhesion molecule-1 expression in mesangial cells and promote leukocyte adhesion through up-regulation of intercellular adhesion molecule-1 through osmotic effect , possibly depending on the protein kinase C nuclear factor-kappa B ( PKC - NF-kappa B ) pathway .", "annotated_text": "CONCLUSION/INTERPRETATION : These results suggest that high glucose can upregulate <protein>intercellular adhesion molecule-1</protein> protein and mRNA expression but not vascular adhesion molecule-1 expression in <cell_type>mesangial cells</cell_type> and promote leukocyte adhesion through up-regulation of <protein>intercellular adhesion molecule-1</protein> through osmotic effect , possibly depending on the <protein>protein kinase C</protein> <protein>nuclear factor-kappa B</protein> ( <protein>PKC</protein> - <protein>NF-kappa B</protein> ) pathway ."}
{"id": "2944", "text": "High glucose itself can also promote mesangial cell proliferation through the PKC-NF-kappa B pathways .", "annotated_text": "High glucose itself can also promote mesangial cell proliferation through the PKC-NF-kappa B pathways ."}
{"id": "2945", "text": "We conclude that hyperglycaemia in itself seems to be an important factor in the development of early diabetic nephropathy .", "annotated_text": "We conclude that hyperglycaemia in itself seems to be an important factor in the development of early diabetic nephropathy ."}
{"id": "2946", "text": "Combined corticosteroid/ granulocyte colony-stimulating factor ( G-CSF ) therapy in the treatment of severe congenital neutropenia unresponsive to G-CSF : Activated glucocorticoid receptors synergize with G-CSF signals .", "annotated_text": "Combined corticosteroid/ <protein>granulocyte colony-stimulating factor</protein> ( <protein>G-CSF</protein> ) therapy in the treatment of severe congenital neutropenia unresponsive to <protein>G-CSF</protein> : Activated <protein>glucocorticoid receptors</protein> synergize with <protein>G-CSF</protein> signals ."}
{"id": "2947", "text": "More than 90 % of patients with severe congenital neutropenia ( SCN ) respond to granulocyte colony-stimulating factor ( G-CSF ) therapy .", "annotated_text": "More than 90 % of patients with severe congenital neutropenia ( SCN ) respond to <protein>granulocyte colony-stimulating factor</protein> ( <protein>G-CSF</protein> ) therapy ."}
{"id": "2948", "text": "The basis for the refractory state in the remaining patients is unknown .", "annotated_text": "The basis for the refractory state in the remaining patients is unknown ."}
{"id": "2949", "text": "To address this issue , we studied a child with SCN who was totally unresponsive to G-CSF and had a novel point mutation in the extracellular domain of the G-CSF receptor ( GCSF-R ) .", "annotated_text": "To address this issue , we studied a child with SCN who was totally unresponsive to <protein>G-CSF</protein> and had a novel point mutation in the <protein>extracellular domain</protein> of the <protein>G-CSF receptor</protein> ( <protein>GCSF-R</protein> ) ."}
{"id": "2950", "text": "Marrow stromal support of granulopoiesis was evaluated by plating CD34 ( + ) cells on preformed stromal layers .", "annotated_text": "Marrow stromal support of granulopoiesis was evaluated by plating <cell_type>CD34 ( + ) cells</cell_type> on preformed stromal layers ."}
{"id": "2951", "text": "Nonadherent cells were harvested and assayed in clonogenic assays for granulocytic colony production .", "annotated_text": "<cell_type>Nonadherent cells</cell_type> were harvested and assayed in clonogenic assays for granulocytic colony production ."}
{"id": "2952", "text": "The in vitro effect of G-CSF and corticosteroids on granulopoiesis was evaluated in clonogenic assays of marrow mononuclear cells , by proliferation studies of the murine myeloid cell line 32D expressing the patient 's mutated G-CSFR , and by measuring STAT5 activation in nuclear extracts from stimulated cells .", "annotated_text": "The in vitro effect of <protein>G-CSF</protein> and corticosteroids on granulopoiesis was evaluated in clonogenic assays of <cell_type>marrow mononuclear cells</cell_type> , by proliferation studies of the <cell_line>murine myeloid cell line 32D</cell_line> expressing the patient 's <protein>mutated G-CSFR</protein> , and by measuring STAT5 activation in nuclear extracts from <cell_type>stimulated cells</cell_type> ."}
{"id": "2953", "text": "Patient 's stroma supported granulopoiesis derived from control marrow CD34 ( + ) cells in a normal manner .", "annotated_text": "Patient 's stroma supported granulopoiesis derived from control <cell_type>marrow CD34 ( + ) cells</cell_type> in a normal manner ."}
{"id": "2954", "text": "Normal stroma , however , failed to induce granulopoiesis from patient 's CD34 ( + ) cells .", "annotated_text": "Normal stroma , however , failed to induce granulopoiesis from patient 's <cell_type>CD34 ( + ) cells</cell_type> ."}
{"id": "2955", "text": "Clonogenic assays of the patient 's marrow mononuclear cells incorporating either G-CSF or hydrocortisone produced little neutrophil growth .", "annotated_text": "Clonogenic assays of the patient 's <cell_type>marrow mononuclear cells</cell_type> incorporating either <protein>G-CSF</protein> or hydrocortisone produced little neutrophil growth ."}
{"id": "2956", "text": "In contrast , inclusion of both G-CSF and hydrocortisone in the cytokine `` cocktail '' markedly increased the neutrophil numbers .", "annotated_text": "In contrast , inclusion of both <protein>G-CSF</protein> and hydrocortisone in the <protein>cytokine `` cocktail ''</protein> markedly increased the neutrophil numbers ."}
{"id": "2957", "text": "Proliferation of 32D cells expressing the mutated receptor and STAT5 activation were improved by a combination of G-CSF and dexamethasone .", "annotated_text": "Proliferation of <cell_line>32D cells</cell_line> expressing the <protein>mutated receptor</protein> and STAT5 activation were improved by a combination of <protein>G-CSF</protein> and dexamethasone ."}
{"id": "2958", "text": "When small daily doses of oral prednisone were then administered to the patient with conventional doses of subcutaneous G-CSF , the patient responded with increased neutrophil numbers and with a complete reversal of the infectious problems .", "annotated_text": "When small daily doses of oral prednisone were then administered to the patient with conventional doses of <protein>subcutaneous G-CSF</protein> , the patient responded with increased neutrophil numbers and with a complete reversal of the infectious problems ."}
{"id": "2959", "text": "These data provide insight into SCN unresponsive to standard G-CSF treatment and to the potential corrective action of combined treatment with G-CSF and corticosteroids through synergistic activation of STAT5 .", "annotated_text": "These data provide insight into SCN unresponsive to standard <protein>G-CSF</protein> treatment and to the potential corrective action of combined treatment with <protein>G-CSF</protein> and corticosteroids through synergistic activation of <protein>STAT5</protein> ."}
{"id": "2960", "text": "Human renal mesangial cells are a target for the anti-inflammatory action of 9-cis retinoic acid .", "annotated_text": "<cell_type>Human renal mesangial cells</cell_type> are a target for the anti-inflammatory action of 9-cis retinoic acid ."}
{"id": "2961", "text": "Mesangial cells play an active role in the inflammatory response to glomerular injury .", "annotated_text": "<cell_type>Mesangial cells</cell_type> play an active role in the inflammatory response to glomerular injury ."}
{"id": "2962", "text": "We have studied in cultured human mesangial cells ( CHMC ) several effects of 9-cis retinoic acid ( 9-cRA ) , an activator of both retinoic acid receptors ( RARs ) and retinoid X receptors ( RXRs ) .", "annotated_text": "We have studied in <cell_line>cultured human mesangial cells</cell_line> ( <cell_line>CHMC</cell_line> ) several effects of 9-cis retinoic acid ( 9-cRA ) , an activator of both <protein>retinoic acid receptors</protein> ( <protein>RARs</protein> ) and <protein>retinoid X receptors</protein> ( <protein>RXRs</protein> ) ."}
{"id": "2963", "text": "9-cRA inhibited foetal calf serum-induced CHMC proliferation .", "annotated_text": "9-cRA inhibited foetal calf serum-induced <cell_line>CHMC</cell_line> proliferation ."}
{"id": "2964", "text": "It also prevented CHMC death induced by the inflammatory mediator H ( 2 ) O ( 2 ) .", "annotated_text": "It also prevented <cell_line>CHMC</cell_line> death induced by the inflammatory mediator H ( 2 ) O ( 2 ) ."}
{"id": "2965", "text": "This preventive effect was not due to any increase in H ( 2 ) O ( 2 ) catabolism and it persisted even when both catalase and glutathione synthesis were inhibited .", "annotated_text": "This preventive effect was not due to any increase in H ( 2 ) O ( 2 ) catabolism and it persisted even when both catalase and glutathione synthesis were inhibited ."}
{"id": "2966", "text": "Finally , 9-cRA diminished monocyte adhesion to FCS-stimulated CHMC .", "annotated_text": "Finally , 9-cRA diminished monocyte adhesion to <cell_line>FCS-stimulated CHMC</cell_line> ."}
{"id": "2967", "text": "Interestingly , the retinoid also inhibited in FCS-stimulated cells the protein expression of two mesangial adhesion molecules , fibronectin and osteopontin , but it did not modify the protein expression of intercellular adhesion molecule-1 and vascular adhesion molecule-1 .", "annotated_text": "Interestingly , the retinoid also inhibited in <cell_type>FCS-stimulated cells</cell_type> the protein expression of two <protein>mesangial adhesion molecules</protein> , <protein>fibronectin</protein> and <protein>osteopontin</protein> , but it did not modify the protein expression of <protein>intercellular adhesion molecule-1</protein> and <protein>vascular adhesion molecule-1</protein> ."}
{"id": "2968", "text": "All major RARs and RXRs isotypes were expressed in CHMC regardless of the presence or absence of 9-cRA .", "annotated_text": "All major <protein>RARs and RXRs isotypes</protein> were expressed in <cell_line>CHMC</cell_line> regardless of the presence or absence of 9-cRA ."}
{"id": "2969", "text": "Transcripts to RAR-alpha , RAR-beta and RXR-alpha increased after incubation with 9-cRA whereas RXR-gamma was inhibited , suggesting a major role for RARs and RXRs in 9-cRA-anti-inflammatory effects .", "annotated_text": "Transcripts to <rna>RAR-alpha</rna> , <rna>RAR-beta</rna> and <rna>RXR-alpha</rna> increased after incubation with 9-cRA whereas <rna>RXR-gamma</rna> was inhibited , suggesting a major role for <protein>RARs</protein> and <protein>RXRs</protein> in 9-cRA-anti-inflammatory effects ."}
{"id": "2970", "text": "9-cRA was toxic only at 50 microM ( a concentration 50 - 5000 times higher than required for the effects above ) .", "annotated_text": "9-cRA was toxic only at 50 microM ( a concentration 50 - 5000 times higher than required for the effects above ) ."}
{"id": "2971", "text": "Cell death occurred by apoptosis , whose onset was associated with a pronounced increase in catalase activity and reduced glutathione content , being more effectively induced by all-trans retinoic acid .", "annotated_text": "Cell death occurred by apoptosis , whose onset was associated with a pronounced increase in catalase activity and reduced glutathione content , being more effectively induced by all-trans retinoic acid ."}
{"id": "2972", "text": "Modulation of the oxidant/antioxidant balance failed to inhibit apoptosis .", "annotated_text": "Modulation of the oxidant/antioxidant balance failed to inhibit apoptosis ."}
{"id": "2973", "text": "We conclude that mesangial cells might be a target for the treatment of inflammatory glomerulopathies with 9-cRA .", "annotated_text": "We conclude that <cell_type>mesangial cells</cell_type> might be a target for the treatment of inflammatory glomerulopathies with 9-cRA ."}
{"id": "2974", "text": "Expression of mammalian defensin genes .", "annotated_text": "Expression of <dna>mammalian defensin genes</dna> ."}
{"id": "2975", "text": "Antimicrobial peptides are a prevalent mechanism of host defense found throughout nature .", "annotated_text": "Antimicrobial peptides are a prevalent mechanism of host defense found throughout nature ."}
{"id": "2976", "text": "In mammals , defensins are among the most abundant of these broad-spectrum antibiotics , and are expressed in epithelial and hematopoietic cells .", "annotated_text": "In mammals , <protein>defensins</protein> are among the most abundant of these broad-spectrum antibiotics , and are expressed in <cell_type>epithelial and hematopoietic cells</cell_type> ."}
{"id": "2977", "text": "The defensin peptides are especially abundant in neutrophils ; however , gene expression is limited to the promyelocyte stage .", "annotated_text": "The defensin peptides are especially abundant in <cell_type>neutrophils</cell_type> ; however , gene expression is limited to the promyelocyte stage ."}
{"id": "2978", "text": "In epithelial cells , defensin genes are found as both constitutively expressed and inducible .", "annotated_text": "In <cell_type>epithelial cells</cell_type> , <dna>defensin genes</dna> are found as both constitutively expressed and inducible ."}
{"id": "2979", "text": "Induction has been observed in vitro by stimulation with bacterial lipopolysaccharide as well as inflammatory mediators .", "annotated_text": "Induction has been observed in vitro by stimulation with bacterial lipopolysaccharide as well as inflammatory mediators ."}
{"id": "2980", "text": "In vivo , up-regulation of several defensin genes occurs in both infectious and inflammatory states .", "annotated_text": "In vivo , up-regulation of several <dna>defensin genes</dna> occurs in both infectious and inflammatory states ."}
{"id": "2981", "text": "Gene regulation occurs via signal transduction pathways common to other innate immune responses , utilizing transcription factors such as nuclear factor ( NF ) -kappaB and NF interleukin-6 .", "annotated_text": "Gene regulation occurs via signal transduction pathways common to other innate immune responses , utilizing <protein>transcription factors</protein> such as <protein>nuclear factor ( NF ) -kappaB</protein> and <protein>NF interleukin-6</protein> ."}
{"id": "2982", "text": "Together , the data suggest a broad-based innate host defense whereby potent antimicrobial peptides are present to prevent initial colonization by pathogenic microorganisms .", "annotated_text": "Together , the data suggest a broad-based innate host defense whereby potent antimicrobial peptides are present to prevent initial colonization by pathogenic microorganisms ."}
{"id": "2983", "text": "In addition , the recognition of bacteria coupled with a nascent inflammatory response can bolster this defense by a coordinated up-regulation of the peptides .", "annotated_text": "In addition , the recognition of bacteria coupled with a nascent inflammatory response can bolster this defense by a coordinated up-regulation of the peptides ."}
{"id": "2984", "text": "Multiple signals required for cyclic AMP-responsive element binding protein ( CREB ) binding protein interaction induced by CD3/CD28 costimulation .", "annotated_text": "Multiple signals required for <protein>cyclic AMP-responsive element binding protein</protein> ( <protein>CREB</protein> ) binding protein interaction induced by CD3/CD28 costimulation ."}
{"id": "2985", "text": "The optimal activation of cAMP-responsive element binding protein ( CREB ) , similar to the full activation of T lymphocytes , requires the stimulation of both CD3 and CD28 .", "annotated_text": "The optimal activation of <protein>cAMP-responsive element binding protein</protein> ( <protein>CREB</protein> ) , similar to the full activation of <cell_type>T lymphocytes</cell_type> , requires the stimulation of both <protein>CD3</protein> and <protein>CD28</protein> ."}
{"id": "2986", "text": "Using a reporter system to detect interaction of CREB and CREB-binding protein ( CBP ) , in this study we found that CREB binds to CBP only by engagement of both CD3 and CD28 .", "annotated_text": "Using a reporter system to detect interaction of <protein>CREB</protein> and <protein>CREB-binding protein</protein> ( <protein>CBP</protein> ) , in this study we found that <protein>CREB</protein> binds to <protein>CBP</protein> only by engagement of both <protein>CD3</protein> and <protein>CD28</protein> ."}
{"id": "2987", "text": "CD3/CD28 -promoted CREB - CBP interaction was dependent on p38 mitogen-activated protein kinase ( MAPK ) and calcium/calmodulin-dependent protein kinase ( CaMK ) IV in addition to the previously identified extracellular signal-regulated kinase pathway .", "annotated_text": "<protein>CD3/CD28</protein> -promoted <protein>CREB</protein> - <protein>CBP</protein> interaction was dependent on <protein>p38 mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) and <protein>calcium/calmodulin-dependent protein kinase ( CaMK ) IV</protein> in addition to the previously identified extracellular signal-regulated kinase pathway ."}
{"id": "2988", "text": "Extracellular signal-regulated kinase , CaMKIV , and p38 MAPK were also the kinases involved in CREB Ser ( 133 ) phosphorylation induced by CD3/CD28 .", "annotated_text": "<protein>Extracellular signal-regulated kinase , CaMKIV</protein> , and <protein>p38 MAPK</protein> were also the kinases involved in <protein>CREB</protein> Ser ( 133 ) phosphorylation induced by <protein>CD3/CD28</protein> ."}
{"id": "2989", "text": "A reconstitution experiment illustrated that optimum CREB - CBP interaction and CREB trans-activation were attained when these three kinase pathways were simultaneously activated in T cells .", "annotated_text": "A reconstitution experiment illustrated that optimum <protein>CREB</protein> - <protein>CBP</protein> interaction and <protein>CREB</protein> trans-activation were attained when these three kinase pathways were simultaneously activated in <cell_type>T cells</cell_type> ."}
{"id": "2990", "text": "Our results demonstrate that coordinated activation of different kinases leads to full activation of CREB .", "annotated_text": "Our results demonstrate that coordinated activation of different <protein>kinases</protein> leads to full activation of <protein>CREB</protein> ."}
{"id": "2991", "text": "Notably , CD28 ligation activated p38 MAPK and CaMKIV , the kinases stimulated by CD3 engagement , suggesting that CD28 acts by increasing the activation extent of p38 MAPK and CaMKIV .", "annotated_text": "Notably , CD28 ligation activated <protein>p38 MAPK</protein> and <protein>CaMKIV</protein> , the <protein>kinases</protein> stimulated by CD3 engagement , suggesting that <protein>CD28</protein> acts by increasing the activation extent of <protein>p38 MAPK</protein> and <protein>CaMKIV</protein> ."}
{"id": "2992", "text": "These results support the model of a minimum activation threshold for CREB - CBP interaction that can be reached only when both CD3 and CD28 are stimulated .", "annotated_text": "These results support the model of a minimum activation threshold for <protein>CREB</protein> - <protein>CBP</protein> interaction that can be reached only when both <protein>CD3</protein> and <protein>CD28</protein> are stimulated ."}
{"id": "2993", "text": "The murine IL-2 promoter contains distal regulatory elements responsive to the Ah receptor , a member of the evolutionarily conserved bHLH-PAS transcription factor family .", "annotated_text": "The <dna>murine IL-2 promoter</dna> contains <dna>distal regulatory elements</dna> responsive to the <protein>Ah receptor</protein> , a member of the evolutionarily conserved <protein>bHLH-PAS transcription factor family</protein> ."}
{"id": "2994", "text": "Signaling through the TCR and costimulatory signals primarily control transcription of the IL-2 gene in naive T cells .", "annotated_text": "Signaling through the <protein>TCR</protein> and costimulatory signals primarily control transcription of the <dna>IL-2 gene</dna> in <cell_type>naive T cells</cell_type> ."}
{"id": "2995", "text": "The minimal promoter necessary for this expression lies proximal , between -300 and the transcription start site .", "annotated_text": "The <dna>minimal promoter</dna> necessary for this expression lies proximal , between -300 and the <dna>transcription start site</dna> ."}
{"id": "2996", "text": "We had previously shown that activation of the arylhydrocarbon receptor ( AHR ) , a member of the bHLH-PAS family of transcription factors , leads to increased mRNA expression of IL-2 in murine fetal thymocytes .", "annotated_text": "We had previously shown that activation of the <protein>arylhydrocarbon receptor</protein> ( <protein>AHR</protein> ) , a member of the <protein>bHLH-PAS family of transcription factors</protein> , leads to increased mRNA expression of <rna>IL-2</rna> in <cell_type>murine fetal thymocytes</cell_type> ."}
{"id": "2997", "text": "The AHR is abundant in the thymus and may play a role for the development of the immune system .", "annotated_text": "The <protein>AHR</protein> is abundant in the thymus and may play a role for the development of the immune system ."}
{"id": "2998", "text": "Moreover , its overactivation by chemicals such as dioxins leads to immunosuppression and thymic involution .", "annotated_text": "Moreover , its overactivation by chemicals such as dioxins leads to immunosuppression and thymic involution ."}
{"id": "2999", "text": "Binding motifs for the liganded AHR can be identified in the distal region -1300 to -800 of the mouse IL-2 promoter .", "annotated_text": "Binding motifs for the <protein>liganded AHR</protein> can be identified in the <dna>distal region -1300 to -800</dna> of the <dna>mouse IL-2 promoter</dna> ."}
{"id": "3000", "text": "We show here that these DNA motifs , the so-called dioxin response elements , after binding to the liganded AHR are sufficient to transactivate luciferase expression in a reporter gene system .", "annotated_text": "We show here that these <dna>DNA motifs</dna> , the so-called <dna>dioxin response elements</dna> , after binding to the <protein>liganded AHR</protein> are sufficient to transactivate luciferase expression in a reporter gene system ."}
{"id": "3001", "text": "The IL-2 gene can be induced by the AHR also in thymocytes in vivo after injection of 2 , 3 , 7 , 8-tetrachlorodibenzo-p-dioxin , a potent ligand of the AHR .", "annotated_text": "The <dna>IL-2 gene</dna> can be induced by the <protein>AHR</protein> also in <cell_type>thymocytes</cell_type> in vivo after injection of 2 , 3 , 7 , 8-tetrachlorodibenzo-p-dioxin , a potent ligand of the <protein>AHR</protein> ."}
{"id": "3002", "text": "The AHR mediates the IL-2 induction as shown with AHR -deficient mice .", "annotated_text": "The <protein>AHR</protein> mediates the IL-2 induction as shown with <protein>AHR</protein> -deficient mice ."}
{"id": "3003", "text": "However , in spleen cells in vitro costimulation via the TCR is necessary for optimal IL-2 gene induction .", "annotated_text": "However , in <cell_type>spleen cells</cell_type> in vitro costimulation via the <protein>TCR</protein> is necessary for optimal <dna>IL-2 gene</dna> induction ."}
{"id": "3004", "text": "Thus , the IL-2 promoter region contains novel distal regulatory elements that can be addressed by the AHR to induce IL-2 and can cooperate with the proximal promoter", "annotated_text": "Thus , the <dna>IL-2 promoter region</dna> contains novel <dna>distal regulatory elements</dna> that can be addressed by the <protein>AHR</protein> to induce <dna>IL-2</dna> and can cooperate with the <dna>proximal promoter</dna>"}
{"id": "3005", "text": "Visualization of Syk-antigen receptor interactions using green fluorescent protein : differential roles for Syk and Lyn in the regulation of receptor capping and internalization .", "annotated_text": "Visualization of <protein>Syk-antigen receptor</protein> interactions using <protein>green fluorescent protein</protein> : differential roles for <protein>Syk</protein> and <protein>Lyn</protein> in the regulation of receptor capping and internalization ."}
{"id": "3006", "text": "The cross-linking of the B cell Ag receptor ( BCR ) is coupled to the stimulation of multiple intracellular signal transduction cascades via receptor-associated , protein tyrosine kinases of both the Src and Syk families .", "annotated_text": "The cross-linking of the <protein>B cell Ag receptor</protein> ( <protein>BCR</protein> ) is coupled to the stimulation of multiple intracellular signal transduction cascades via receptor-associated , <protein>protein tyrosine kinases</protein> of both the <protein>Src and Syk families</protein> ."}
{"id": "3007", "text": "To monitor changes in the subcellular distribution of Syk in B cells responding to BCR cross-linking , we expressed in Syk -deficient DT40 B cells a fusion protein consisting of Syk coupled to green fluorescent protein .", "annotated_text": "To monitor changes in the subcellular distribution of <protein>Syk</protein> in <cell_type>B cells</cell_type> responding to <protein>BCR</protein> cross-linking , we expressed in <protein>Syk</protein> -deficient <cell_line>DT40 B cells</cell_line> a <protein>fusion protein</protein> consisting of <protein>Syk</protein> coupled to <protein>green fluorescent protein</protein> ."}
{"id": "3008", "text": "Treatment of these cells with anti-IgM Abs leads to the recruitment of the kinase from cytoplasmic and nuclear compartments to the site of the cross-linked receptor at the plasma membrane .", "annotated_text": "Treatment of these cells with <protein>anti-IgM Abs</protein> leads to the recruitment of the <protein>kinase</protein> from cytoplasmic and nuclear compartments to the site of the <protein>cross-linked receptor</protein> at the plasma membrane ."}
{"id": "3009", "text": "The Syk-receptor complexes aggregate into membrane patches that redistribute to form a cap at one pole of the cell .", "annotated_text": "The <protein>Syk-receptor complexes</protein> aggregate into membrane patches that redistribute to form a cap at one pole of the cell ."}
{"id": "3010", "text": "Syk is not demonstrably associated with the internalized receptor .", "annotated_text": "<protein>Syk</protein> is not demonstrably associated with the <protein>internalized receptor</protein> ."}
{"id": "3011", "text": "Catalytically active Syk promotes and stabilizes the formation of tightly capped BCR complexes at the plasma membrane .", "annotated_text": "Catalytically active <protein>Syk</protein> promotes and stabilizes the formation of <protein>tightly capped BCR complexes</protein> at the plasma membrane ."}
{"id": "3012", "text": "Lyn is not required for the recruitment of Syk to the cross-linked receptor , but is required for the internalization of the clustered BCR complexes .", "annotated_text": "<protein>Lyn</protein> is not required for the recruitment of <protein>Syk</protein> to the <protein>cross-linked receptor</protein> , but is required for the internalization of the clustered <protein>BCR complexes</protein> ."}
{"id": "3013", "text": "In the absence of Lyn , receptor-Syk complexes at the plasma membrane are long lived , and the receptor-mediated activation of the NF-AT transcription factor is enhanced .", "annotated_text": "In the absence of <protein>Lyn</protein> , <protein>receptor-Syk complexes</protein> at the plasma membrane are long lived , and the receptor-mediated activation of the <protein>NF-AT transcription factor</protein> is enhanced ."}
{"id": "3014", "text": "Thus , Lyn appears to function to negatively regulate aspects of BCR -dependent signaling by stimulating receptor internalization and down-regulation .", "annotated_text": "Thus , <protein>Lyn</protein> appears to function to negatively regulate aspects of <protein>BCR</protein> -dependent signaling by stimulating receptor internalization and down-regulation ."}
{"id": "3015", "text": "Renal interstitial fibrosis is reduced in angiotensin II type 1a receptor -deficient mice .", "annotated_text": "Renal interstitial fibrosis is reduced in <protein>angiotensin II type 1a receptor</protein> -deficient mice ."}
{"id": "3016", "text": "Unilateral ureteral obstruction ( UUO ) results in tubulointerstitial fibrosis of the affected kidney by stimulating the renin-angiotensin system .", "annotated_text": "Unilateral ureteral obstruction ( UUO ) results in tubulointerstitial fibrosis of the affected kidney by stimulating the renin-angiotensin system ."}
{"id": "3017", "text": "This study established a UUO model in angiotensin type 1a receptor ( AT1a ) deficient ( mutant ) mice to elucidate the role of angiotensin II through AT1a on the fibrosis of the obstructed kidney ( OBK ) .", "annotated_text": "This study established a UUO model in <protein>angiotensin type 1a receptor</protein> ( <protein>AT1a</protein> ) deficient ( mutant ) mice to elucidate the role of <protein>angiotensin II</protein> through <protein>AT1a</protein> on the fibrosis of the obstructed kidney ( OBK ) ."}
{"id": "3018", "text": "The relative volume of the tubulointerstitium was measured by an image analyzer ; deposition of collagen types III and IV and monocyte / macrophage infiltration were histologically examined using specific antibodies .", "annotated_text": "The relative volume of the tubulointerstitium was measured by an image analyzer ; deposition of <protein>collagen types III and IV</protein> and <cell_type>monocyte</cell_type> / <cell_type>macrophage</cell_type> infiltration were histologically examined using <protein>specific antibodies</protein> ."}
{"id": "3019", "text": "Also determined were the mRNA levels of transforming growth factor-beta by Northern blot analysis .", "annotated_text": "Also determined were the mRNA levels of <protein>transforming growth factor-beta</protein> by Northern blot analysis ."}
{"id": "3020", "text": "Nuclear factor-kappaB activity was assessed by gel shift assay .", "annotated_text": "<protein>Nuclear factor-kappaB</protein> activity was assessed by gel shift assay ."}
{"id": "3021", "text": "UUO in wild mice resulted in a marked expansion of relative volume of the tubulointerstitium , together with increased deposition of collagen types III and IV and number of infiltrated monocytes / macrophages in the interstitium , relative to sham-operated mice .", "annotated_text": "UUO in wild mice resulted in a marked expansion of relative volume of the tubulointerstitium , together with increased deposition of <protein>collagen types III and IV</protein> and number of infiltrated <cell_type>monocytes</cell_type> / <cell_type>macrophages</cell_type> in the interstitium , relative to sham-operated mice ."}
{"id": "3022", "text": "In comparison , these changes were significantly lower in mutant mice with UUO .", "annotated_text": "In comparison , these changes were significantly lower in mutant mice with UUO ."}
{"id": "3023", "text": "The mRNA level of transforming growth factor-beta was significantly higher in the OBK of wild mice with UUO compared with sham-operated mice .", "annotated_text": "The mRNA level of <protein>transforming growth factor-beta</protein> was significantly higher in the OBK of wild mice with UUO compared with sham-operated mice ."}
{"id": "3024", "text": "In contrast , the increase in mRNA level in the OBK of mutant mice was significantly less than in wild mice .", "annotated_text": "In contrast , the increase in mRNA level in the OBK of mutant mice was significantly less than in wild mice ."}
{"id": "3025", "text": "Finally , UUO resulted in activation of nuclear factor-kappaB in wild mice but was inhibited in the OBK of mutant mice .", "annotated_text": "Finally , UUO resulted in activation of <protein>nuclear factor-kappaB</protein> in wild mice but was inhibited in the OBK of mutant mice ."}
{"id": "3026", "text": "The results provide direct evidence that angiotensin II acting via the AT1a plays a pivotal role in the development of tubulointerstitial fibrosis in UUO .", "annotated_text": "The results provide direct evidence that <protein>angiotensin II</protein> acting via the <protein>AT1a</protein> plays a pivotal role in the development of tubulointerstitial fibrosis in UUO ."}
{"id": "3027", "text": "HLA-DQ tetramers identify epitope-specific T cells in peripheral blood of herpes simplex virus type 2-infected individuals : direct detection of immunodominant antigen-responsive cells .", "annotated_text": "<protein>HLA-DQ tetramers</protein> identify <cell_type>epitope-specific T cells</cell_type> in peripheral blood of herpes simplex virus type 2-infected individuals : direct detection of <cell_type>immunodominant antigen-responsive cells</cell_type> ."}
{"id": "3028", "text": "Ag-specific CD4+ T cells are present in peripheral blood in low frequency , where they undergo recruitment and expansion during immune responses and in the pathogenesis of numerous autoimmune diseases .", "annotated_text": "<cell_type>Ag-specific CD4+ T cells</cell_type> are present in peripheral blood in low frequency , where they undergo recruitment and expansion during immune responses and in the pathogenesis of numerous autoimmune diseases ."}
{"id": "3029", "text": "MHC tetramers , which constitute a labeled MHC-peptide ligand suitable for binding to the Ag-specific receptor on T cells , provide a novel approach for the detection and characterization of such rare cells .", "annotated_text": "<protein>MHC tetramers</protein> , which constitute a <protein>labeled MHC-peptide ligand</protein> suitable for binding to the <protein>Ag-specific receptor</protein> on <cell_type>T cells</cell_type> , provide a novel approach for the detection and characterization of such <cell_type>rare cells</cell_type> ."}
{"id": "3030", "text": "In this study , we utilized this technology to identify HLA DQ -restricted Ag-specific T cells in the peripheral blood of human subjects and to identify immunodominant epitopes associated with viral infection .", "annotated_text": "In this study , we utilized this technology to identify <protein>HLA DQ</protein> -restricted <cell_type>Ag-specific T cells</cell_type> in the peripheral blood of human subjects and to identify immunodominant epitopes associated with viral infection ."}
{"id": "3031", "text": "Peptides representing potential epitope regions of the VP16 protein from HSV-2 were loaded onto recombinant DQ0602 molecules to generate a panel of Ag-specific DQ0602 tetramers .", "annotated_text": "Peptides representing potential <protein>epitope regions</protein> of the <protein>VP16 protein</protein> from HSV-2 were loaded onto <protein>recombinant DQ0602 molecules</protein> to generate a panel of <protein>Ag-specific DQ0602 tetramers</protein> ."}
{"id": "3032", "text": "VP16 Ag -specific DQ-restricted T cells were identified and expanded from the peripheral blood of HSV-2-infected individuals , representing two predominant epitope specificities .", "annotated_text": "<protein>VP16 Ag</protein> -specific <cell_type>DQ-restricted T cells</cell_type> were identified and expanded from the peripheral blood of HSV-2-infected individuals , representing two predominant epitope specificities ."}
{"id": "3033", "text": "Although the VP16 369-380 peptide has a lower binding affinity for DQ0602 molecules than the VP16 33-52 peptide , T cells that recognized the VP16 369-380 peptide occurred at a much higher frequency than those that were specific for the VP16 33-52 peptide .", "annotated_text": "Although the VP16 369-380 peptide has a lower binding affinity for <protein>DQ0602 molecules</protein> than the VP16 33-52 peptide , <cell_type>T cells</cell_type> that recognized the VP16 369-380 peptide occurred at a much higher frequency than those that were specific for the VP16 33-52 peptide ."}
{"id": "3034", "text": "Down-regulation of BOB.1/OBF.1 and Oct2 in classical Hodgkin disease but not in lymphocyte predominant Hodgkin disease correlates with immunoglobulin transcription .", "annotated_text": "Down-regulation of <protein>BOB.1/OBF.1</protein> and <protein>Oct2</protein> in classical Hodgkin disease but not in lymphocyte predominant Hodgkin disease correlates with immunoglobulin transcription ."}
{"id": "3035", "text": "In contrast to the tumor cells ( L & H cells ) of lymphocyte predominant Hodgkin disease ( LPHD ) , Hodgkin and Reed-Sternberg ( HRS ) cells of classical Hodgkin disease ( cHD ) are unable to transcribe immunoglobulin , despite the presence of rearranged immunoglobulin genes .", "annotated_text": "In contrast to the <cell_type>tumor cells</cell_type> ( <cell_type>L & H cells</cell_type> ) of lymphocyte predominant Hodgkin disease ( LPHD ) , <cell_type>Hodgkin and Reed-Sternberg ( HRS ) cells</cell_type> of classical Hodgkin disease ( cHD ) are unable to transcribe <protein>immunoglobulin</protein> , despite the presence of <dna>rearranged immunoglobulin genes</dna> ."}
{"id": "3036", "text": "Although initial studies have suggested crippling immunoglobulin gene mutations to be the cause of absent immunoglobulin expression in cHD , recent work of our group has demonstrated an impaired activation of the immunoglobulin promoter as a superior mechanism .", "annotated_text": "Although initial studies have suggested crippling immunoglobulin gene mutations to be the cause of absent immunoglobulin expression in cHD , recent work of our group has demonstrated an impaired activation of the <dna>immunoglobulin promoter</dna> as a superior mechanism ."}
{"id": "3037", "text": "As immunoglobulin transcription is mainly regulated by the B-cell transcription factors Oct2 and BOB.1/OBF.1 , we analyzed 35 cases of LPHD , 32 cases of cHD , and 2 Hodgkin disease cell lines for the expression of these transcription factors and also in parallel for immunoglobulin expression .", "annotated_text": "As immunoglobulin transcription is mainly regulated by the <protein>B-cell transcription factors</protein> <protein>Oct2</protein> and <protein>BOB.1/OBF.1</protein> , we analyzed 35 cases of LPHD , 32 cases of cHD , and 2 <cell_line>Hodgkin disease cell lines</cell_line> for the expression of these <protein>transcription factors</protein> and also in parallel for immunoglobulin expression ."}
{"id": "3038", "text": "Our results demonstrate an absence of Oct2 and/or BOB.1/OBF.1 in cHD and a striking overexpression of Oct2 in LPHD .", "annotated_text": "Our results demonstrate an absence of <protein>Oct2</protein> and/or <protein>BOB.1/OBF.1</protein> in cHD and a striking overexpression of <protein>Oct2</protein> in LPHD ."}
{"id": "3039", "text": "Immunoglobulin expression was lacking in cHD but present in LPHD .", "annotated_text": "Immunoglobulin expression was lacking in cHD but present in LPHD ."}
{"id": "3040", "text": "Furthermore , the reintroduction of BOB.1/OBF.1 and Oct2 into cultured HRS cells restored the activity of cotransduced immunoglobulin promoter constructs .", "annotated_text": "Furthermore , the reintroduction of <protein>BOB.1/OBF.1</protein> and <protein>Oct2</protein> into cultured <cell_type>HRS cells</cell_type> restored the activity of cotransduced <dna>immunoglobulin promoter constructs</dna> ."}
{"id": "3041", "text": "Our findings dismiss the concept that the different immunoglobulin expression in cHD and LPHD is due to disrupting mutations of immunoglobulin V genes in cHD but is most likely due to a down-regulation of Oct2 and/or BOB.1/OBF.1 .", "annotated_text": "Our findings dismiss the concept that the different immunoglobulin expression in cHD and LPHD is due to disrupting mutations of <dna>immunoglobulin V genes</dna> in cHD but is most likely due to a down-regulation of <protein>Oct2</protein> and/or <protein>BOB.1/OBF.1</protein> ."}
{"id": "3042", "text": "This study further revealed Oct2 as a new and valuable marker for the identification of L & H cells and their distinction from HRS cells .", "annotated_text": "This study further revealed <protein>Oct2</protein> as a new and valuable marker for the identification of <cell_type>L & H cells</cell_type> and their distinction from <cell_type>HRS cells</cell_type> ."}
{"id": "3043", "text": "The impairment of immunoglobulin transcription with a down-regulated synthesis of Oct2 and BOB.1/OBF.1 is the first established general recurrent defect found in HRS cells .", "annotated_text": "The impairment of immunoglobulin transcription with a down-regulated synthesis of <protein>Oct2</protein> and <protein>BOB.1/OBF.1</protein> is the first established general recurrent defect found in <cell_type>HRS cells</cell_type> ."}
{"id": "3044", "text": "Constitutive expression of NF-kappa B is a characteristic feature of mycosis fungoides : implications for apoptosis resistance and pathogenesis .", "annotated_text": "Constitutive expression of <protein>NF-kappa B</protein> is a characteristic feature of mycosis fungoides : implications for apoptosis resistance and pathogenesis ."}
{"id": "3045", "text": "The NF-kappa B family of transcription factors is an important regulator of genes expressed during inflammatory responses , immunoglobulin ( Ig ) class switching , cellular differentiation , and apoptosis .", "annotated_text": "The <protein>NF-kappa B family of transcription factors</protein> is an important regulator of genes expressed during inflammatory responses , immunoglobulin ( Ig ) class switching , cellular differentiation , and apoptosis ."}
{"id": "3046", "text": "Recently , members of the NF-kappaB family , including p65 ( Rel A ) , have been implicated in promoting survival of various hematopoeitic neoplasms , including T cell malignancies such as adult T cell leukemia-lymphoma .", "annotated_text": "Recently , members of the <protein>NF-kappaB family</protein> , including <protein>p65 ( Rel A )</protein> , have been implicated in promoting survival of various hematopoeitic neoplasms , including T cell malignancies such as adult T cell leukemia-lymphoma ."}
{"id": "3047", "text": "We investigated the expression of active NF-kappa B p65 ( Rel A ) in cases of mycosis fungoides ( MF ) and the effect of chemical inhibitors of NF-kappa B on apoptosis in cutaneous T cell lymphoma ( CTCL ) cell lines .", "annotated_text": "We investigated the expression of <protein>active NF-kappa B p65 ( Rel A )</protein> in cases of mycosis fungoides ( MF ) and the effect of chemical inhibitors of <protein>NF-kappa B</protein> on apoptosis in <cell_line>cutaneous T cell lymphoma ( CTCL ) cell lines</cell_line> ."}
{"id": "3048", "text": "Paraffin-embedded tissues from 23 cutaneous lesions and a single lymph node biopsy from patients diagnosed with MF were evaluated for p65 ( Rel A ) expression by using a monoclonal mouse antibody that detects the activated form of p65 ( Rel A ) .", "annotated_text": "Paraffin-embedded tissues from 23 cutaneous lesions and a single lymph node biopsy from patients diagnosed with MF were evaluated for p65 ( Rel A ) expression by using a <protein>monoclonal mouse antibody</protein> that detects the activated form of <protein>p65 ( Rel A )</protein> ."}
{"id": "3049", "text": "Apoptosis after treatment with the NF-kappa B inhibitors gliotoxin , MG132 , BAY 11-7082 , and BAY 11-7085 was quantitatively measured in the CTCL cell lines HuT-78 and HH by propidium iodide ( PI ) /cell cycle analysis for detection of a hypodiploid ( sub-G ( 0 ) ) population and by determination of increased Annexin V/7-amino-actinomycin D ( 7-AAD ) expression .", "annotated_text": "Apoptosis after treatment with the NF-kappa B inhibitors gliotoxin , MG132 , BAY 11-7082 , and BAY 11-7085 was quantitatively measured in the <cell_line>CTCL cell lines HuT-78 and HH</cell_line> by propidium iodide ( PI ) /cell cycle analysis for detection of a hypodiploid ( sub-G ( 0 ) ) population and by determination of increased Annexin V/7-amino-actinomycin D ( 7-AAD ) expression ."}
{"id": "3050", "text": "Nuclear extracts from CTCL cells before and after chemical inhibition were analyzed for NF-kappa B nuclear DNA-binding activity by electrophoretic mobility shift assay ( EMSA ) with quantitative densitometry .", "annotated_text": "Nuclear extracts from <cell_type>CTCL cells</cell_type> before and after chemical inhibition were analyzed for NF-kappa B nuclear DNA-binding activity by electrophoretic mobility shift assay ( EMSA ) with quantitative densitometry ."}
{"id": "3051", "text": "Nuclear expression of p65 ( Rel A ) before and after treatment with the various inhibitory compounds was measured by immunofluorescence staining in each CTCL cell line .", "annotated_text": "Nuclear expression of <protein>p65 ( Rel A )</protein> before and after treatment with the various inhibitory compounds was measured by immunofluorescence staining in each <cell_line>CTCL cell line</cell_line> ."}
{"id": "3052", "text": "Neoplastic T lymphocytes from 22 of 24 cases of MF showed strong nuclear and cytoplasmic expression of active p65 ( Rel A ) .", "annotated_text": "<cell_type>Neoplastic T lymphocytes</cell_type> from 22 of 24 cases of MF showed strong nuclear and cytoplasmic expression of <protein>active p65 ( Rel A )</protein> ."}
{"id": "3053", "text": "Compared with untreated control cells , a marked increase in apoptosis , a significant decrease in NF-kappa B DNA-binding activity , and a marked decrease in nuclear p65 ( Rel A ) expression were seen in cells from both CTCL cell lines after chemical NF-kappa B inhibition .", "annotated_text": "Compared with untreated <cell_type>control cells</cell_type> , a marked increase in apoptosis , a significant decrease in NF-kappa B DNA-binding activity , and a marked decrease in nuclear p65 ( Rel A ) expression were seen in cells from both <cell_line>CTCL cell lines</cell_line> after chemical NF-kappa B inhibition ."}
{"id": "3054", "text": "These data show that the active form of NF-kappa B p65 ( Rel A ) is commonly expressed in neoplastic T lymphocytes in patients with MF .", "annotated_text": "These data show that the active form of <protein>NF-kappa B p65 ( Rel A )</protein> is commonly expressed in <cell_type>neoplastic T lymphocytes</cell_type> in patients with MF ."}
{"id": "3055", "text": "In CTCL cell lines , the significant decrease in nuclear NF-kappa B expression and the marked increase in spontaneous apoptosis caused by chemical NF-kappa B inhibition suggest a critical role for NF-kappa B in the pathogenesis and tumor cell maintenance of CTCLs .", "annotated_text": "In <cell_line>CTCL cell lines</cell_line> , the significant decrease in nuclear NF-kappa B expression and the marked increase in spontaneous apoptosis caused by chemical NF-kappa B inhibition suggest a critical role for <protein>NF-kappa B</protein> in the pathogenesis and tumor cell maintenance of CTCLs ."}
{"id": "3056", "text": "HUM PATHOL 31 : 1482-1490 .", "annotated_text": "HUM PATHOL 31 : 1482-1490 ."}
{"id": "3057", "text": "Human T-cell leukemia virus type 1 tax protein activates transcription through AP-1 site by inducing DNA binding activity in T cells .", "annotated_text": "Human T-cell leukemia virus type 1 <protein>tax protein</protein> activates transcription through <dna>AP-1 site</dna> by inducing DNA binding activity in <cell_type>T cells</cell_type> ."}
{"id": "3058", "text": "Human T-cell leukemia virus type 1 ( HTLV-1 ) Tax protein induces the expression of various family members of the transcription factor AP-1 , such as c-Jun , JunD , c-Fos , and Fra-1 , at the level of RNA expression in T cells .", "annotated_text": "Human T-cell leukemia virus type 1 ( HTLV-1 ) <protein>Tax protein</protein> induces the expression of various family members of the <protein>transcription factor AP-1</protein> , such as <protein>c-Jun</protein> , <protein>JunD</protein> , <protein>c-Fos</protein> , and <protein>Fra-1</protein> , at the level of RNA expression in <cell_type>T cells</cell_type> ."}
{"id": "3059", "text": "We examined the activity of Tax in transcription through AP-1-binding sites ( AP-1 site ) in T cells .", "annotated_text": "We examined the activity of <protein>Tax</protein> in transcription through <dna>AP-1-binding sites</dna> ( <dna>AP-1 site</dna> ) in <cell_type>T cells</cell_type> ."}
{"id": "3060", "text": "Transient transfection studies showed that Tax activated the expression of a luciferase gene regulated by two copies of an AP-1 site in the human Jurkat T-cell line .", "annotated_text": "Transient transfection studies showed that <protein>Tax</protein> activated the expression of a <dna>luciferase gene</dna> regulated by two copies of an <dna>AP-1 site</dna> in the <cell_line>human Jurkat T-cell line</cell_line> ."}
{"id": "3061", "text": "Tax activates the expression of viral and cellular genes through two different enhancers : a cAMP-responsive ( CRE ) -like element and a kappaB element .", "annotated_text": "<protein>Tax</protein> activates the expression of <dna>viral and cellular genes</dna> through two different enhancers : a <dna>cAMP-responsive ( CRE ) -like element</dna> and a <dna>kappaB element</dna> ."}
{"id": "3062", "text": "Two Tax mutants differentially activated expression of these two elements .", "annotated_text": "Two <protein>Tax mutants</protein> differentially activated expression of these two elements ."}
{"id": "3063", "text": "Tax703 preferentially activated the kappaB element but not the CRE-like one , whereas TaxM22 showed the reverse .", "annotated_text": "<protein>Tax703</protein> preferentially activated the <dna>kappaB element</dna> but not the CRE-like one , whereas <protein>TaxM22</protein> showed the reverse ."}
{"id": "3064", "text": "In addition , Tax703 and Tax , but not TaxM22 , converted cell growth of a mouse T-cell line from being interleukin ( IL ) -2-dependent to being IL-2-independent .", "annotated_text": "In addition , <protein>Tax703</protein> and <protein>Tax</protein> , but not <protein>TaxM22</protein> , converted cell growth of a <cell_line>mouse T-cell line</cell_line> from being interleukin ( IL ) -2-dependent to being IL-2-independent ."}
{"id": "3065", "text": "Unlike the wild-type Tax , Tax703 and TaxM22 only weakly activated the AP-1 site in the T-cell line .", "annotated_text": "Unlike the <protein>wild-type Tax</protein> , <protein>Tax703</protein> and <protein>TaxM22</protein> only weakly activated the <dna>AP-1 site</dna> in the <cell_line>T-cell line</cell_line> ."}
{"id": "3066", "text": "Thus , Tax seems to activate the AP-1 site via mechanisms distinct from those of kappaB or CRE-like elements , and the activation of the AP-1 site is dispensable for IL-2-independent growth of CTLL-2 .", "annotated_text": "Thus , <protein>Tax</protein> seems to activate the <dna>AP-1 site</dna> via mechanisms distinct from those of <dna>kappaB or CRE-like elements</dna> , and the activation of the <dna>AP-1 site</dna> is dispensable for IL-2-independent growth of CTLL-2 ."}
{"id": "3067", "text": "Electrophoretic mobility shift assays showed that Tax induced strong binding activity to an AP-1 site in CTLL-2 , whereas Tax703 did not , indicating that the induction of binding activity to the AP-1 site is essential for the transcriptional activation by Tax .", "annotated_text": "Electrophoretic mobility shift assays showed that <protein>Tax</protein> induced strong binding activity to an <dna>AP-1 site</dna> in CTLL-2 , whereas <protein>Tax703</protein> did not , indicating that the induction of binding activity to the <dna>AP-1 site</dna> is essential for the transcriptional activation by <protein>Tax</protein> ."}
{"id": "3068", "text": "The binding complex induced by Tax in CTLL-2 contained JunD and Fra-2 .", "annotated_text": "The <protein>binding complex</protein> induced by <protein>Tax</protein> in CTLL-2 contained <protein>JunD</protein> and <protein>Fra-2</protein> ."}
{"id": "3069", "text": "Other AP-1 proteins were undetectable .", "annotated_text": "Other <protein>AP-1 proteins</protein> were undetectable ."}
{"id": "3070", "text": "Activation of transcription through the AP-1 site in Jurkat cells by JunD and/or Fra-2 was weak .", "annotated_text": "Activation of transcription through the <dna>AP-1 site</dna> in <cell_line>Jurkat cells</cell_line> by <protein>JunD</protein> and/or <protein>Fra-2</protein> was weak ."}
{"id": "3071", "text": "c-Jun , JunB , and c-Fos activation was greater , although the level was still less than that with Tax .", "annotated_text": "<protein>c-Jun</protein> , <protein>JunB</protein> , and <protein>c-Fos</protein> activation was greater , although the level was still less than that with <protein>Tax</protein> ."}
{"id": "3072", "text": "Thus , the induction of AP-1 mRNA by Tax may not be sufficient for a complete activation of AP-1 site by Tax .", "annotated_text": "Thus , the induction of <rna>AP-1 mRNA</rna> by <protein>Tax</protein> may not be sufficient for a complete activation of <dna>AP-1 site</dna> by <protein>Tax</protein> ."}
{"id": "3073", "text": "Our results suggest that Tax activates the transcription of cellular genes with AP-1 sites by inducing the DNA-binding activity of AP-1 proteins in T cells , a mechanism distinct from those of CRE-like and kappaB elements .", "annotated_text": "Our results suggest that <protein>Tax</protein> activates the transcription of <dna>cellular genes</dna> with <dna>AP-1 sites</dna> by inducing the DNA-binding activity of <protein>AP-1 proteins</protein> in <cell_type>T cells</cell_type> , a mechanism distinct from those of <dna>CRE-like and kappaB elements</dna> ."}
{"id": "3074", "text": "Copyright 2001 Academic Press .", "annotated_text": "Copyright 2001 Academic Press ."}
{"id": "3075", "text": "Strict control of human immunodeficiency virus type 1 replication by a genetic switch : Tet for Tat .", "annotated_text": "Strict control of human immunodeficiency virus type 1 replication by a genetic switch : Tet for Tat ."}
{"id": "3076", "text": "Live-attenuated human immunodeficiency virus type 1 ( HIV-1 ) variants have shown great promise as AIDS vaccines , but continued replication can lead to the selection of faster-replicating variants that are pathogenic .", "annotated_text": "Live-attenuated human immunodeficiency virus type 1 ( HIV-1 ) variants have shown great promise as AIDS vaccines , but continued replication can lead to the selection of faster-replicating variants that are pathogenic ."}
{"id": "3077", "text": "We therefore designed HIV-1 genomes that replicate exclusively upon addition of the nontoxic effector doxycycline ( dox ) .", "annotated_text": "We therefore designed <dna>HIV-1 genomes</dna> that replicate exclusively upon addition of the nontoxic effector doxycycline ( dox ) ."}
{"id": "3078", "text": "This was achieved by replacement of the viral TAR-Tat system for transcriptional activation by the Escherichia coli-derived Tet system for inducible gene expression .", "annotated_text": "This was achieved by replacement of the viral TAR-Tat system for transcriptional activation by the Escherichia coli-derived Tet system for inducible gene expression ."}
{"id": "3079", "text": "These designer `` HIV-rtTA '' viruses replicate in a strictly dox-dependent manner both in a T-cell line and in primary blood cells , and the rate of replication can be fine-tuned by simple variation of the dox concentration .", "annotated_text": "These designer `` HIV-rtTA '' viruses replicate in a strictly dox-dependent manner both in a <cell_line>T-cell line</cell_line> and in <cell_type>primary blood cells</cell_type> , and the rate of replication can be fine-tuned by simple variation of the dox concentration ."}
{"id": "3080", "text": "These HIV-rtTA viruses provide a tool to perform genetics , e.g. , selection and optimization experiments , with the E. coli-derived Tet reagents in a eukaryotic background .", "annotated_text": "These HIV-rtTA viruses provide a tool to perform genetics , e.g. , selection and optimization experiments , with the E. coli-derived Tet reagents in a eukaryotic background ."}
{"id": "3081", "text": "Furthermore , such viruses may represent improved vaccine candidates because their replication can be turned on and off at will .", "annotated_text": "Furthermore , such viruses may represent improved vaccine candidates because their replication can be turned on and off at will ."}
{"id": "3082", "text": "Synovial fluid induced nuclear factor-kappaB DNA binding in a monocytic cell line .", "annotated_text": "Synovial fluid induced <protein>nuclear factor-kappaB</protein> DNA binding in a <cell_line>monocytic cell line</cell_line> ."}
{"id": "3083", "text": "OBJECTIVE : To determine the effects of synovial fluids ( SF ) on DNA binding activity of transcription factor nuclear factor-kappaB ( NF-kappaB ) in the Mono Mac 6 monocytic/macrophage cell line as a model for the interaction between SF and synovial tissue macrophages in arthritis .", "annotated_text": "OBJECTIVE : To determine the effects of synovial fluids ( SF ) on DNA binding activity of <protein>transcription factor</protein> <protein>nuclear factor-kappaB</protein> ( <protein>NF-kappaB</protein> ) in the <cell_line>Mono Mac 6 monocytic/macrophage cell line</cell_line> as a model for the interaction between SF and <cell_type>synovial tissue macrophages</cell_type> in arthritis ."}
{"id": "3084", "text": "METHODS : Mono Mac 6 cells were incubated with SF from the knee joints of human subjects with rheumatoid arthritis ( RA ) , undifferentiated seronegative oligoarthritis , and osteoarthritis ( OA ) .", "annotated_text": "METHODS : <cell_line>Mono Mac 6 cells</cell_line> were incubated with SF from the knee joints of human subjects with rheumatoid arthritis ( RA ) , undifferentiated seronegative oligoarthritis , and osteoarthritis ( OA ) ."}
{"id": "3085", "text": "Nuclear extracts prepared from the Mono Mac 6 cells and RA synovial tissue were analyzed by electrophoretic mobility shift analysis ( EMSA ) for NF-kappaB DNA binding proteins .", "annotated_text": "Nuclear extracts prepared from the <cell_line>Mono Mac 6 cells</cell_line> and RA synovial tissue were analyzed by electrophoretic mobility shift analysis ( EMSA ) for <protein>NF-kappaB DNA binding proteins</protein> ."}
{"id": "3086", "text": "RESULTS : Induction of NF-kappaB DNA binding by the p65 ( RelA ) /p50 heterodimer was observed in response to incubation of Mono Mac 6 cells with SF ( 20 % in culture medium ) from 5 of 8 subjects with RA , 4 of 5 with OA , and none of 3 with undifferentiated seronegative oligoarthritis .", "annotated_text": "RESULTS : Induction of <protein>NF-kappaB</protein> DNA binding by the <protein>p65 ( RelA ) /p50 heterodimer</protein> was observed in response to incubation of <cell_line>Mono Mac 6 cells</cell_line> with SF ( 20 % in culture medium ) from 5 of 8 subjects with RA , 4 of 5 with OA , and none of 3 with undifferentiated seronegative oligoarthritis ."}
{"id": "3087", "text": "Incubation of SF with neutralizing antibodies against tumor necrosis factor-alpha ( TNF-alpha ) , but not antibodies against interleukin 6 ( IL-6 ) , significantly reduced the induction of p65/p50 binding activity in SF from subjects with RA and OA .", "annotated_text": "Incubation of SF with <protein>neutralizing antibodies</protein> against <protein>tumor necrosis factor-alpha ( TNF-alpha )</protein> , but not <protein>antibodies</protein> against <protein>interleukin 6 ( IL-6 )</protein> , significantly reduced the induction of p65/p50 binding activity in SF from subjects with RA and OA ."}
{"id": "3088", "text": "Unexpectedly , a slowly migrating SF inducible NF-kappaB -binding complex was observed in EMSA of Mono Mac 6 cells after incubation with SF from 5 of 8 RA and 2 of 5 OA subjects .", "annotated_text": "Unexpectedly , a slowly migrating SF inducible <protein>NF-kappaB</protein> -binding complex was observed in EMSA of <cell_line>Mono Mac 6 cells</cell_line> after incubation with SF from 5 of 8 RA and 2 of 5 OA subjects ."}
{"id": "3089", "text": "The induction of this complex by SF was not affected by neutralization of TNF-alpha or IL-6 in SF , and the complex was not inducible by TNF-alpha , IL-1beta , TNF-alpha / IL-1beta , IL-6 , platelet derived growth factor , lipopolysaccharide , or tetradecanoyl phorbol acetate .", "annotated_text": "The induction of this complex by SF was not affected by neutralization of <protein>TNF-alpha</protein> or <protein>IL-6</protein> in SF , and the complex was not inducible by <protein>TNF-alpha</protein> , IL-1beta , <protein>TNF-alpha</protein> / <protein>IL-1beta</protein> , <protein>IL-6</protein> , <protein>platelet derived growth factor</protein> , lipopolysaccharide , or tetradecanoyl phorbol acetate ."}
{"id": "3090", "text": "The slowly migrating complex could not be supershifted with antibodies against NF-kappaB , Jun , or the transcriptional coactivators p300 or CBP .", "annotated_text": "The slowly <protein>migrating complex</protein> could not be supershifted with <protein>antibodies</protein> against <protein>NF-kappaB</protein> , <protein>Jun</protein> , or the transcriptional coactivators <protein>p300</protein> or <protein>CBP</protein> ."}
{"id": "3091", "text": "A NF-kappaB-binding complex with similar slow mobility was observed in nuclear extracts prepared from fresh human RA synovial tissue .", "annotated_text": "A <protein>NF-kappaB-binding complex</protein> with similar slow mobility was observed in nuclear extracts prepared from fresh human RA synovial tissue ."}
{"id": "3092", "text": "CONCLUSION : Biological activity of TNF-alpha in SF from RA and OA subjects is capable of inducing p65/p50 NF-kappaB DNA binding activity in macrophages .", "annotated_text": "CONCLUSION : Biological activity of <protein>TNF-alpha</protein> in SF from RA and OA subjects is capable of inducing <protein>p65/p50 NF-kappaB</protein> DNA binding activity in <cell_type>macrophages</cell_type> ."}
{"id": "3093", "text": "A property of SF that is independent of TNF-alpha and other cytokines is responsible for the induction of a novel slowly migrating NF-kappaB-binding complex .", "annotated_text": "A property of SF that is independent of <protein>TNF-alpha</protein> and other <protein>cytokines</protein> is responsible for the induction of a novel slowly migrating <protein>NF-kappaB-binding complex</protein> ."}
{"id": "3094", "text": "Soluble mediators in SF of subjects with RA and OA can therefore modulate binding of nuclear proteins to the NF-kappaB binding site in macrophages and may play a role in inflammatory gene expression in arthritis .", "annotated_text": "Soluble mediators in SF of subjects with RA and OA can therefore modulate binding of <protein>nuclear proteins</protein> to the <protein>NF-kappaB binding site</protein> in <cell_type>macrophages</cell_type> and may play a role in inflammatory gene expression in arthritis ."}
{"id": "3095", "text": "Peroxisome proliferator activator receptor-gamma agonists and 15-deoxy-Delta ( 12 , 14 ) ( 12 , 14 ) -PGJ ( 2 ) induce apoptosis in normal and malignant B-lineage cells .", "annotated_text": "<protein>Peroxisome proliferator activator receptor-gamma</protein> agonists and 15-deoxy-Delta ( 12 , 14 ) ( 12 , 14 ) -PGJ ( 2 ) induce apoptosis in normal and malignant <cell_type>B-lineage cells</cell_type> ."}
{"id": "3096", "text": "The research described herein evaluates the expression and functional significance of peroxisome proliferator activator receptor-gamma ( PPAR-gamma ) on B-lineage cells .", "annotated_text": "The research described herein evaluates the expression and functional significance of <protein>peroxisome proliferator activator receptor-gamma ( PPAR-gamma )</protein> on <cell_type>B-lineage cells</cell_type> ."}
{"id": "3097", "text": "Normal mouse B cells and a variety of B lymphoma cells reflective of stages of B cell differentiation ( e.g. , 70Z/3 , CH31 , WEHI-231 , CH12 , and J558 ) express PPAR-gamma mRNA and , by Western blot analysis , the 67-kDa PPAR-gamma protein .", "annotated_text": "<cell_type>Normal mouse B cells</cell_type> and a variety of <cell_type>B lymphoma cells</cell_type> reflective of stages of B cell differentiation ( e.g. , 70Z/3 , CH31 , WEHI-231 , CH12 , and J558 ) express <rna>PPAR-gamma mRNA</rna> and , by Western blot analysis , the <protein>67-kDa PPAR-gamma protein</protein> ."}
{"id": "3098", "text": "15-Deoxy-Delta ( 12 , 14 ) -PGJ ( 2 ) ( 15d-PGJ ( 2 ) ) , a PPAR-gamma agonist , has a dose-dependent antiproliferative and cytotoxic effect on normal and malignant B cells as shown by [ ( 3 ) H ] thymidine and 3- [ 4 , 5-dimethylthiazol-2-yl ] -2 , 5-diphenyltetrazolium bromide assays .", "annotated_text": "15-Deoxy-Delta ( 12 , 14 ) -PGJ ( 2 ) ( 15d-PGJ ( 2 ) ) , a PPAR-gamma agonist , has a dose-dependent antiproliferative and cytotoxic effect on <cell_type>normal and malignant B cells</cell_type> as shown by [ ( 3 ) H ] thymidine and 3- [ 4 , 5-dimethylthiazol-2-yl ] -2 , 5-diphenyltetrazolium bromide assays ."}
{"id": "3099", "text": "Only PPAR-gamma agonists ( thiazolidinediones ) , and not PPAR-alpha agonists , mimicked the effect of 15d-PGJ ( 2 ) on B-lineage cells , indicating that the mechanism by which 15d-PGJ ( 2 ) negatively affects B-lineage cells involves in part PPAR-gamma .", "annotated_text": "Only PPAR-gamma agonists ( thiazolidinediones ) , and not PPAR-alpha agonists , mimicked the effect of 15d-PGJ ( 2 ) on <cell_type>B-lineage cells</cell_type> , indicating that the mechanism by which 15d-PGJ ( 2 ) negatively affects <cell_type>B-lineage cells</cell_type> involves in part <protein>PPAR-gamma</protein> ."}
{"id": "3100", "text": "The mechanism by which PPAR-gamma agonists induce cytotoxicity is via apoptosis , as shown by annexin V staining and as confirmed by DNA fragmentation detected using the TUNEL assay .", "annotated_text": "The mechanism by which PPAR-gamma agonists induce cytotoxicity is via apoptosis , as shown by annexin V staining and as confirmed by DNA fragmentation detected using the TUNEL assay ."}
{"id": "3101", "text": "Interestingly , addition of PGF ( 2alpha ) , which was not known to affect lymphocytes , dramatically attenuated the deleterious effects of PPAR-gamma agonists on B lymphomas .", "annotated_text": "Interestingly , addition of PGF ( 2alpha ) , which was not known to affect <cell_type>lymphocytes</cell_type> , dramatically attenuated the deleterious effects of PPAR-gamma agonists on <cell_type>B lymphomas</cell_type> ."}
{"id": "3102", "text": "Surprisingly , 15d-PGJ ( 2 ) induced a massive increase in nuclear mitogen-activated protein kinase activation , and pretreatment with PGF ( 2alpha ) blunted the mitogen-activated protein kinase activation .", "annotated_text": "Surprisingly , 15d-PGJ ( 2 ) induced a massive increase in nuclear mitogen-activated protein kinase activation , and pretreatment with PGF ( 2alpha ) blunted the mitogen-activated protein kinase activation ."}
{"id": "3103", "text": "This is the first study evaluating PPAR-gamma expression and its significance on B lymphocytes .", "annotated_text": "This is the first study evaluating PPAR-gamma expression and its significance on <cell_type>B lymphocytes</cell_type> ."}
{"id": "3104", "text": "PPAR-gamma agonists may serve as a counterbalance to the stimulating effects of other PGs , namely PGE ( 2 ) , which promotes B cell differentiation .", "annotated_text": "PPAR-gamma agonists may serve as a counterbalance to the stimulating effects of other PGs , namely PGE ( 2 ) , which promotes B cell differentiation ."}
{"id": "3105", "text": "Finally , the use of PGs , such as 15d-PGJ ( 2 ) , and synthetic PPAR-gamma agonists to induce apoptosis in B-lineage cells may lead to the development of novel therapies for fatal B lymphomas", "annotated_text": "Finally , the use of PGs , such as 15d-PGJ ( 2 ) , and synthetic PPAR-gamma agonists to induce apoptosis in <cell_type>B-lineage cells</cell_type> may lead to the development of novel therapies for <cell_type>fatal B lymphomas</cell_type>"}
{"id": "3106", "text": "Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression .", "annotated_text": "Inhibition of STAT3 signaling leads to apoptosis of <cell_type>leukemic large granular lymphocytes</cell_type> and decreased Mcl-1 expression ."}
{"id": "3107", "text": "Large granular lymphocyte ( LGL ) leukemia is characterized by the expansion of antigen-activated cytotoxic T lymphocytes .", "annotated_text": "Large granular lymphocyte ( LGL ) leukemia is characterized by the expansion of <cell_type>antigen-activated cytotoxic T lymphocytes</cell_type> ."}
{"id": "3108", "text": "These leukemic cells are resistant to Fas-mediated apoptosis despite expressing high levels of Fas .", "annotated_text": "These <cell_type>leukemic cells</cell_type> are resistant to Fas-mediated apoptosis despite expressing high levels of <protein>Fas</protein> ."}
{"id": "3109", "text": "We found that leukemic LGL from 19 patients displayed high levels of activated STAT3 .", "annotated_text": "We found that <cell_type>leukemic LGL</cell_type> from 19 patients displayed high levels of <protein>activated STAT3</protein> ."}
{"id": "3110", "text": "Treatment of leukemic LGL with the JAK-selective tyrosine kinase inhibitor AG-490 induced apoptosis with a corresponding decrease in STAT -DNA binding activity .", "annotated_text": "Treatment of <cell_type>leukemic LGL</cell_type> with the JAK-selective tyrosine kinase inhibitor AG-490 induced apoptosis with a corresponding decrease in <protein>STAT</protein> -DNA binding activity ."}
{"id": "3111", "text": "Moreover , using an antisense oligonucleotide approach to diminish STAT3 expression , we found that Fas sensitivity was restored in leukemic LGL .", "annotated_text": "Moreover , using an antisense oligonucleotide approach to diminish STAT3 expression , we found that Fas sensitivity was restored in <cell_type>leukemic LGL</cell_type> ."}
{"id": "3112", "text": "AG-490-induced apoptosis in leukemic LGL was independent of Bcl-xL or Bcl-2 expression .", "annotated_text": "AG-490-induced apoptosis in <cell_type>leukemic LGL</cell_type> was independent of Bcl-xL or Bcl-2 expression ."}
{"id": "3113", "text": "However , we found that the Bcl-2-family protein Mcl-1 was significantly reduced by AG-490 treatment .", "annotated_text": "However , we found that the <protein>Bcl-2-family protein Mcl-1</protein> was significantly reduced by AG-490 treatment ."}
{"id": "3114", "text": "Activated STAT3 was shown to bind an SIE-related element in the murine mcl-1 promoter .", "annotated_text": "<protein>Activated STAT3</protein> was shown to bind an <dna>SIE-related element</dna> in the <dna>murine mcl-1 promoter</dna> ."}
{"id": "3115", "text": "Using a luciferase reporter assay , we demonstrated that v-src overexpression in NIH3T3 induced STAT3 -dependent transcriptional activity from the mcl-1 promoter and increased endogenous Mcl-1 protein levels .", "annotated_text": "Using a luciferase reporter assay , we demonstrated that v-src overexpression in NIH3T3 induced <protein>STAT3</protein> -dependent transcriptional activity from the <dna>mcl-1 promoter</dna> and increased endogenous Mcl-1 protein levels ."}
{"id": "3116", "text": "We conclude that STAT3 activation contributed to accumulation of the leukemic LGL clones .", "annotated_text": "We conclude that <protein>STAT3</protein> activation contributed to accumulation of the <cell_type>leukemic LGL clones</cell_type> ."}
{"id": "3117", "text": "These findings suggest that investigation should focus on novel strategies targeting STAT3 in the treatment of LGL leukemia .", "annotated_text": "These findings suggest that investigation should focus on novel strategies targeting <protein>STAT3</protein> in the treatment of LGL leukemia ."}
{"id": "3118", "text": "Decreased immediate inflammatory gene induction in activating transcription factor-2 mutant mice .", "annotated_text": "Decreased immediate <dna>inflammatory gene</dna> induction in <protein>activating transcription factor-2</protein> mutant mice ."}
{"id": "3119", "text": "Transcription factor activating transcription factor ( ATF ) -2 is activated by inflammatory signals transduced by the JNK and p38 MAP kinase pathways .", "annotated_text": "<protein>Transcription factor activating transcription factor ( ATF ) -2</protein> is activated by inflammatory signals transduced by the JNK and p38 MAP kinase pathways ."}
{"id": "3120", "text": "To better define the role of ATF-2 in inflammation , adult mice expressing small amounts of a mutant ATF-2 protein were challenged with lipopolysaccharide ( LPS ) , anti-CD3 antibody or virus .", "annotated_text": "To better define the role of <protein>ATF-2</protein> in inflammation , adult mice expressing small amounts of a <protein>mutant ATF-2 protein</protein> were challenged with lipopolysaccharide ( LPS ) , <protein>anti-CD3 antibody</protein> or virus ."}
{"id": "3121", "text": "Within 3 h of challenge by LPS , ATF-2 mutant mice had decreased induction of the adhesion molecules E-selectin , P-selectin and VCAM-1 as well as the cytokines tumor necrosis factor-alpha , IL-1beta and IL-6 compared with control mice .", "annotated_text": "Within 3 h of challenge by LPS , ATF-2 mutant mice had decreased induction of the <protein>adhesion molecules</protein> <protein>E-selectin</protein> , <protein>P-selectin</protein> and <protein>VCAM-1</protein> as well as the <protein>cytokines</protein> <protein>tumor necrosis factor-alpha</protein> , <protein>IL-1beta</protein> and <protein>IL-6</protein> compared with control mice ."}
{"id": "3122", "text": "Stimulation of T lymphocytes by anti-CD3 antibody also showed less induction of IL-1 and IL-6 in ATF-2 mutant tissues .", "annotated_text": "Stimulation of <cell_type>T lymphocytes</cell_type> by <protein>anti-CD3 antibody</protein> also showed less induction of <protein>IL-1</protein> and <protein>IL-6</protein> in ATF-2 mutant tissues ."}
{"id": "3123", "text": "ATF-2 mutant thymocytes treated with anti-CD3 antibody in vitro demonstrated reduced induction of c-Jun , JunB , JunD and Fra-2 .", "annotated_text": "<cell_type>ATF-2 mutant thymocytes</cell_type> treated with <protein>anti-CD3 antibody</protein> in vitro demonstrated reduced induction of <protein>c-Jun</protein> , <protein>JunB</protein> , <protein>JunD</protein> and <protein>Fra-2</protein> ."}
{"id": "3124", "text": "However , similar to what was observed after p38 kinase inhibition in normal mice , relative ATF-2 deficiency did not prevent the development of a mononuclear cell infiltrate in the week following an inflammatory stimulus .", "annotated_text": "However , similar to what was observed after p38 kinase inhibition in normal mice , relative ATF-2 deficiency did not prevent the development of a <cell_type>mononuclear cell</cell_type> infiltrate in the week following an inflammatory stimulus ."}
{"id": "3125", "text": "ATF-2 mutant mice proved more susceptible to death than control mice from LPS plus D-galactosamine injection or Coxsackievirus B3 infection and had a higher incidence of mononuclear pulmonary infiltrates after exposure to Herpes simplex virus-1 .", "annotated_text": "ATF-2 mutant mice proved more susceptible to death than control mice from LPS plus D-galactosamine injection or Coxsackievirus B3 infection and had a higher incidence of mononuclear pulmonary infiltrates after exposure to Herpes simplex virus-1 ."}
{"id": "3126", "text": "ATF-2 is essential for maximal immediate induction of adhesion molecules and cytokine genes , but at later time points may even protect against overactive immune responses .", "annotated_text": "<protein>ATF-2</protein> is essential for maximal immediate induction of <protein>adhesion molecules</protein> and <dna>cytokine genes</dna> , but at later time points may even protect against overactive immune responses ."}
{"id": "3127", "text": "LIGHT , a TNF-like molecule , costimulates T cell proliferation and is required for dendritic cell -mediated allogeneic T cell response .", "annotated_text": "<protein>LIGHT</protein> , a <protein>TNF-like molecule</protein> , costimulates T cell proliferation and is required for <cell_type>dendritic cell</cell_type> -mediated allogeneic T cell response ."}
{"id": "3128", "text": "LIGHT is a recently identified member of the TNF superfamily and its receptors , herpesvirus entry mediator and lymphotoxin beta receptor , are found in T cells and stromal cells .", "annotated_text": "<protein>LIGHT</protein> is a recently identified member of the <protein>TNF superfamily</protein> and its receptors , <protein>herpesvirus entry mediator</protein> and <protein>lymphotoxin beta receptor</protein> , are found in <cell_type>T cells</cell_type> and <cell_type>stromal cells</cell_type> ."}
{"id": "3129", "text": "In this study , we demonstrate that LIGHT is selectively expressed on immature dendritic cells ( DCs ) generated from human PBMCs .", "annotated_text": "In this study , we demonstrate that <protein>LIGHT</protein> is selectively expressed on <cell_type>immature dendritic cells</cell_type> ( <cell_type>DCs</cell_type> ) generated from <cell_type>human PBMCs</cell_type> ."}
{"id": "3130", "text": "In contrast , LIGHT is not detectable in DCs either freshly isolated from PBMCs or rendered mature in vitro by LPS treatment .", "annotated_text": "In contrast , <protein>LIGHT</protein> is not detectable in <cell_type>DCs</cell_type> either freshly isolated from <cell_type>PBMCs</cell_type> or rendered mature in vitro by LPS treatment ."}
{"id": "3131", "text": "Blockade of LIGHT by its soluble receptors , lymphotoxin beta receptor-Ig or HVEM-Ig , inhibits the induction of DC -mediated primary allogeneic T cell response .", "annotated_text": "Blockade of <protein>LIGHT</protein> by its <protein>soluble receptors</protein> , <protein>lymphotoxin beta receptor-Ig</protein> or <protein>HVEM-Ig</protein> , inhibits the induction of <cell_type>DC</cell_type> -mediated primary allogeneic T cell response ."}
{"id": "3132", "text": "Furthermore , engagement of LIGHT costimulates human T cell proliferation , amplifies the NF-kappaB signaling pathway , and preferentially induces the production of IFN-gamma , but not IL-4 , in the presence of an antigenic signal .", "annotated_text": "Furthermore , engagement of <protein>LIGHT</protein> costimulates human T cell proliferation , amplifies the NF-kappaB signaling pathway , and preferentially induces the production of <protein>IFN-gamma</protein> , but not <protein>IL-4</protein> , in the presence of an antigenic signal ."}
{"id": "3133", "text": "Our results suggest that LIGHT is a costimulatory molecule involved in DC -mediated cellular immune responses .", "annotated_text": "Our results suggest that <protein>LIGHT</protein> is a <protein>costimulatory molecule</protein> involved in <cell_type>DC</cell_type> -mediated cellular immune responses ."}
{"id": "3134", "text": "Suppression of HIV type 1 replication by a dominant-negative Ets-1 mutant .", "annotated_text": "Suppression of HIV type 1 replication by a <protein>dominant-negative Ets-1 mutant</protein> ."}
{"id": "3135", "text": "Activity of the distal region of the human immunodeficiency virus ( HIV-1 ) long terminal repeat ( LTR ) , which contains binding sites for the Ets-1 and USF-1 proteins , is integral for HIV-1 replication .", "annotated_text": "Activity of the <dna>distal region</dna> of the human immunodeficiency virus ( HIV-1 ) <dna>long terminal repeat</dna> ( <dna>LTR</dna> ) , which contains <dna>binding sites</dna> for the <protein>Ets-1 and USF-1 proteins</protein> , is integral for HIV-1 replication ."}
{"id": "3136", "text": "The Ets-1 and USF-1 proteins play a critical role in the activity of the HIV-1 LTR distal enhancer region , as indicated by the potent dominant negative effect of a mutant Ets-1 lacking trans-activation domains on the transcriptional activity of the LTR .", "annotated_text": "The <protein>Ets-1 and USF-1 proteins</protein> play a critical role in the activity of the <dna>HIV-1 LTR distal enhancer region</dna> , as indicated by the potent dominant negative effect of a <dna>mutant Ets-1 lacking trans-activation domains</dna> on the transcriptional activity of the <dna>LTR</dna> ."}
{"id": "3137", "text": "To determine the biological relevance of the Ets-1 and USF-1 proteins in HIV-1 replication , we examined the effect of expression of the dominant-negative mutant of Ets-1 ( dnEts-1 ) on HIV-1 infection of T cells .", "annotated_text": "To determine the biological relevance of the <protein>Ets-1 and USF-1 proteins</protein> in HIV-1 replication , we examined the effect of expression of the dominant-negative mutant of <dna>Ets-1</dna> ( <dna>dnEts-1</dna> ) on HIV-1 infection of <cell_type>T cells</cell_type> ."}
{"id": "3138", "text": "We demonstrated that expression of dnEts markedly suppressed HIV-1 infection of a T cell line .", "annotated_text": "We demonstrated that expression of <dna>dnEts</dna> markedly suppressed HIV-1 infection of a <cell_line>T cell line</cell_line> ."}
{"id": "3139", "text": "This finding indicates that formation of a transcriptionaly active USF-1/Ets-1 complex is important in the productive infection of cells by HIV-1 , and suggests that inhibition of the interaction between USF-1 and Ets-1 with the HIV-1 LTR may provide a new target for anti-HIV-1 gene therapy .", "annotated_text": "This finding indicates that formation of a <protein>transcriptionaly active USF-1/Ets-1 complex</protein> is important in the productive infection of cells by HIV-1 , and suggests that inhibition of the interaction between <protein>USF-1</protein> and <protein>Ets-1</protein> with the <dna>HIV-1 LTR</dna> may provide a new target for anti-HIV-1 gene therapy ."}
{"id": "3140", "text": "Human eosinophils constitutively express nuclear factor of activated T cells p and c .", "annotated_text": "<cell_type>Human eosinophils</cell_type> constitutively express <protein>nuclear factor of activated T cells p and c</protein> ."}
{"id": "3141", "text": "BACKGROUND : Eosinophils are now known to produce a variety of proinflammatory cytokines , although the molecular factors that regulate their production are poorly understood .", "annotated_text": "BACKGROUND : <cell_type>Eosinophils</cell_type> are now known to produce a variety of <protein>proinflammatory cytokines</protein> , although the molecular factors that regulate their production are poorly understood ."}
{"id": "3142", "text": "The expression of almost all of the cytokines produced by eosinophils , including the proallergic cytokine IL-4 , is now known to be regulated at the level of transcription by members of the nuclear factor of activated T cells ( NFAT ) family of transcription factors .", "annotated_text": "The expression of almost all of the <protein>cytokines</protein> produced by <cell_type>eosinophils</cell_type> , including the <protein>proallergic cytokine IL-4</protein> , is now known to be regulated at the level of transcription by members of the <protein>nuclear factor of activated T cells</protein> ( <protein>NFAT</protein> ) family of transcription factors ."}
{"id": "3143", "text": "OBJECTIVE : We sought to characterize the expression of different NFAT proteins in resting and activated eosinophils .", "annotated_text": "OBJECTIVE : We sought to characterize the expression of different <protein>NFAT proteins</protein> in <cell_type>resting and activated eosinophils</cell_type> ."}
{"id": "3144", "text": "METHODS : Nuclear and whole cell extracts were obtained from both peripheral blood eosinophils and those obtained from bronchoalveolar lavage fluid of asthmatic subjects after endobronchial allergen challenge .", "annotated_text": "METHODS : Nuclear and whole cell extracts were obtained from both <cell_type>peripheral blood eosinophils</cell_type> and those obtained from bronchoalveolar lavage fluid of asthmatic subjects after endobronchial allergen challenge ."}
{"id": "3145", "text": "NFAT expression was determined by using immunoprecipitation and Western blot analysis , DNA-binding assays , and RT-PCR analysis of eosinophil mRNA .", "annotated_text": "<protein>NFAT</protein> expression was determined by using immunoprecipitation and Western blot analysis , DNA-binding assays , and RT-PCR analysis of <rna>eosinophil mRNA</rna> ."}
{"id": "3146", "text": "RESULTS : Both peripheral blood and bronchoalveolar lavage fluid eosinophils expressed NFATp and NFATc protein .", "annotated_text": "RESULTS : Both <cell_type>peripheral blood and bronchoalveolar lavage fluid eosinophils</cell_type> expressed <protein>NFATp and NFATc protein</protein> ."}
{"id": "3147", "text": "Unlike activated T cells , which express multiple NFATc isoforms , eosinophils preferentially express the approximately 85-kd isoform .", "annotated_text": "Unlike <cell_type>activated T cells</cell_type> , which express multiple NFATc isoforms , <cell_type>eosinophils</cell_type> preferentially express the approximately 85-kd isoform ."}
{"id": "3148", "text": "In addition , eosinophils were found to constitutively express NFATc mRNA .", "annotated_text": "In addition , <cell_type>eosinophils</cell_type> were found to constitutively express <rna>NFATc mRNA</rna> ."}
{"id": "3149", "text": "A brief incubation with the T ( H ) 2 cytokines IL-4 and IL-5 was sufficient to induce the nuclear translocation of NFATc .", "annotated_text": "A brief incubation with the <protein>T ( H ) 2 cytokines</protein> <protein>IL-4</protein> and <protein>IL-5</protein> was sufficient to induce the nuclear translocation of <protein>NFATc</protein> ."}
{"id": "3150", "text": "Eosinophil nuclear extracts contain multiple factors that can specifically recognize the IL-4 promoter P1 NFAT site in DNA-binding assays , including NFATp .", "annotated_text": "Eosinophil nuclear extracts contain multiple factors that can specifically recognize the <dna>IL-4 promoter P1 NFAT site</dna> in DNA-binding assays , including <protein>NFATp</protein> ."}
{"id": "3151", "text": "CONCLUSION : NFATp and NFATc can regulate the expression of cytokines and other genes in eosinophils but appear to be regulated by a novel signal transduction mechanism in these cells .", "annotated_text": "CONCLUSION : <protein>NFATp</protein> and <protein>NFATc</protein> can regulate the expression of <protein>cytokines</protein> and other genes in <cell_type>eosinophils</cell_type> but appear to be regulated by a novel signal transduction mechanism in these cells ."}
{"id": "3152", "text": "BLyS BINDS TO B CELLS WITH HIGH AFFINITY AND INDUCES ACTIVATION OF THE TRANSCRIPTION FACTORS NF-kappaB AND ELF-1 .", "annotated_text": "<protein>BLyS</protein> BINDS TO <cell_type>B CELLS</cell_type> WITH HIGH AFFINITY AND INDUCES ACTIVATION OF THE <protein>TRANSCRIPTION FACTORS</protein> <protein>NF-kappaB</protein> AND <protein>ELF-1</protein> ."}
{"id": "3153", "text": "B lymphocyte stimulator ( BLyS ) is a novel member of the TNF family of proteins expressed by myeloid cells as membrane-bound and soluble forms .", "annotated_text": "<protein>B lymphocyte stimulator</protein> ( <protein>BLyS</protein> ) is a novel member of the <protein>TNF family of proteins</protein> expressed by <cell_type>myeloid cells</cell_type> as membrane-bound and soluble forms ."}
{"id": "3154", "text": "BLyS was shown to act specifically on B cells , inducing proliferation and immunoglobulin production both in vitro and in vivo .", "annotated_text": "<protein>BLyS</protein> was shown to act specifically on <cell_type>B cells</cell_type> , inducing proliferation and immunoglobulin production both in vitro and in vivo ."}
{"id": "3155", "text": "The present study was undertaken to characterize binding of radiolabeled BLyS to its cognate receptor on human B lymphocytes and examine intracellular events initiated by BLyS binding .", "annotated_text": "The present study was undertaken to characterize binding of <protein>radiolabeled BLyS</protein> to its <protein>cognate receptor</protein> on <cell_type>human B lymphocytes</cell_type> and examine intracellular events initiated by <protein>BLyS</protein> binding ."}
{"id": "3156", "text": "Similar to other TNF family members , BLyS is present in solution as a homotrimer as determined by gel filtration chromatography and light scattering analysis .", "annotated_text": "Similar to other <protein>TNF family members</protein> , <protein>BLyS</protein> is present in solution as a <protein>homotrimer</protein> as determined by gel filtration chromatography and light scattering analysis ."}
{"id": "3157", "text": "BLyS binding to B cells is specific as other TNF family members tested did not compete for ( 125 ) I- BLyS binding .", "annotated_text": "<protein>BLyS</protein> binding to <cell_type>B cells</cell_type> is specific as other <protein>TNF family members</protein> tested did not compete for ( 125 ) I- <protein>BLyS</protein> binding ."}
{"id": "3158", "text": "Analysis of equilibrium binding of ( 125 ) I-labeled BLyS to purified human tonsillar B cells demonstrated saturable binding .", "annotated_text": "Analysis of equilibrium binding of <protein>( 125 ) I-labeled BLyS</protein> to purified <cell_type>human tonsillar B cells</cell_type> demonstrated saturable binding ."}
{"id": "3159", "text": "Scatchard analysis of the binding data revealed a single class of high-affinity binding on human B cells with approximately 2600 binding sites per cell and an apparent dissociation constant ( K ( D ) ) of about 0.1 nM .", "annotated_text": "Scatchard analysis of the binding data revealed a single class of high-affinity binding on <cell_type>human B cells</cell_type> with approximately 2600 binding sites per cell and an apparent dissociation constant ( K ( D ) ) of about 0.1 nM ."}
{"id": "3160", "text": "In addition we report that BLyS binding to B cells results in the activation of NF-kappaB and the Ets family transcription factor , ELF-1 , and in the induction of mRNA for Polo-like kinase ( PLK ) .", "annotated_text": "In addition we report that <protein>BLyS</protein> binding to <cell_type>B cells</cell_type> results in the activation of <protein>NF-kappaB</protein> and the <protein>Ets family transcription factor</protein> , <protein>ELF-1</protein> , and in the induction of mRNA for <protein>Polo-like kinase</protein> ( <protein>PLK</protein> ) ."}
{"id": "3161", "text": "Copyright 2001 Academic Press .", "annotated_text": "Copyright 2001 Academic Press ."}
{"id": "3162", "text": "Design and use of an inducibly activated human immunodeficiency virus type 1 Nef to study immune modulation .", "annotated_text": "Design and use of an inducibly activated human immunodeficiency virus type 1 <protein>Nef</protein> to study immune modulation ."}
{"id": "3163", "text": "The Nef protein of the human immunodeficiency virus type 1 ( HIV-1 ) has been shown to enhance the infectivity of virus particles , downmodulate cell surface proteins , and associate with many intracellular proteins that are thought to facilitate HIV infection .", "annotated_text": "The <protein>Nef protein</protein> of the human immunodeficiency virus type 1 ( HIV-1 ) has been shown to enhance the infectivity of virus particles , downmodulate <protein>cell surface proteins</protein> , and associate with many <protein>intracellular proteins</protein> that are thought to facilitate HIV infection ."}
{"id": "3164", "text": "One of the challenges in defining the molecular events regulated by Nef has been obtaining good expression of Nef protein in T cells .", "annotated_text": "One of the challenges in defining the molecular events regulated by <protein>Nef</protein> has been obtaining good expression of <protein>Nef protein</protein> in <cell_type>T cells</cell_type> ."}
{"id": "3165", "text": "This has been attributed to effects of Nef on cell proliferation and apoptosis .", "annotated_text": "This has been attributed to effects of <protein>Nef</protein> on cell proliferation and apoptosis ."}
{"id": "3166", "text": "We have designed a Nef protein that is readily expressed in T-cell lines and whose function is inducibly activated .", "annotated_text": "We have designed a <protein>Nef protein</protein> that is readily expressed in <cell_line>T-cell lines</cell_line> and whose function is inducibly activated ."}
{"id": "3167", "text": "It is composed of a fusion between full-length Nef and the estrogen receptor hormone-binding domain ( Nef-ER ) .", "annotated_text": "It is composed of a fusion between <protein>full-length Nef</protein> and the <protein>estrogen receptor hormone-binding domain</protein> ( <protein>Nef-ER</protein> ) ."}
{"id": "3168", "text": "The Nef-ER is kept in an inactive state due to steric hindrance , and addition of the membrane-permeable drug 4-hydroxytamoxifen ( 4-HT ) , which binds to the ER domain , leads to inducible activation of Nef-ER within cells .", "annotated_text": "The <protein>Nef-ER</protein> is kept in an inactive state due to steric hindrance , and addition of the membrane-permeable drug 4-hydroxytamoxifen ( 4-HT ) , which binds to the <protein>ER domain</protein> , leads to inducible activation of <protein>Nef-ER</protein> within cells ."}
{"id": "3169", "text": "We demonstrate that Nef-ER inducibly associates with the 62-kDa Ser/Thr kinase and is localized to specific membrane microdomains ( lipid rafts ) only after activation .", "annotated_text": "We demonstrate that <protein>Nef-ER</protein> inducibly associates with the <protein>62-kDa Ser/Thr kinase</protein> and is localized to specific membrane microdomains ( lipid rafts ) only after activation ."}
{"id": "3170", "text": "Using this inducible Nef , we also compared the specific requirements for CD4 and HLA-A2 downmodulation in a SupT1 T-cell line .", "annotated_text": "Using this inducible <protein>Nef</protein> , we also compared the specific requirements for <protein>CD4</protein> and <protein>HLA-A2</protein> downmodulation in a <cell_line>SupT1 T-cell line</cell_line> ."}
{"id": "3171", "text": "Half-maximal downmodulation of cell surface CD4 required very little active Nef-ER and occurred as early as 4 h after addition of 4-HT .", "annotated_text": "Half-maximal downmodulation of <protein>cell surface CD4</protein> required very little active <protein>Nef-ER</protein> and occurred as early as 4 h after addition of 4-HT ."}
{"id": "3172", "text": "In contrast , 50 % downmodulation of HLA-A2 by Nef required 16 to 24 h and about 50- to 100-fold-greater concentrations of 4-HT .", "annotated_text": "In contrast , 50 % downmodulation of <protein>HLA-A2</protein> by <protein>Nef</protein> required 16 to 24 h and about 50- to 100-fold-greater concentrations of 4-HT ."}
{"id": "3173", "text": "These data suggest that HLA-A2 downmodulation may require certain threshold levels of active Nef .", "annotated_text": "These data suggest that <protein>HLA-A2</protein> downmodulation may require certain threshold levels of active <protein>Nef</protein> ."}
{"id": "3174", "text": "The differential timing of CD4 and HLA-A2 downmodulation may have implications for HIV pathogenesis and immune evasion .", "annotated_text": "The differential timing of <protein>CD4</protein> and <protein>HLA-A2</protein> downmodulation may have implications for HIV pathogenesis and immune evasion ."}
{"id": "3175", "text": "Regulation of chemokine mRNA expression in a rat model of vanadium-induced pulmonary inflammation .", "annotated_text": "Regulation of chemokine mRNA expression in a rat model of vanadium-induced pulmonary inflammation ."}
{"id": "3176", "text": "Environmental and occupational exposure to vanadium dusts results in toxic effects mainly confined to the respiratory system .", "annotated_text": "Environmental and occupational exposure to vanadium dusts results in toxic effects mainly confined to the respiratory system ."}
{"id": "3177", "text": "Using a rat model of acute lung inflammation induced by intratracheal instillation of sodium metavanadate ( NaVO3 ) at the dose of 200 microg V/kg , we investigated the relationship between the cytologic characterization of pulmonary inflammation and the expression of chemokine mRNA .", "annotated_text": "Using a rat model of acute lung inflammation induced by intratracheal instillation of sodium metavanadate ( NaVO3 ) at the dose of 200 microg V/kg , we investigated the relationship between the cytologic characterization of pulmonary inflammation and the expression of <rna>chemokine mRNA</rna> ."}
{"id": "3178", "text": "Significant polymorphonuclear leukocyte ( PMN ) influx ( P < 0.01 ) into the lung was noted 4 h after NaVO3 instillation , whereas alveolar macrophages ( AMs ) in bronchoalveolar lavage ( BAL ) cells appeared to decrease significantly .", "annotated_text": "Significant <cell_type>polymorphonuclear leukocyte</cell_type> ( <cell_type>PMN</cell_type> ) influx ( P < 0.01 ) into the lung was noted 4 h after NaVO3 instillation , whereas <cell_type>alveolar macrophages</cell_type> ( <cell_type>AMs</cell_type> ) in <cell_type>bronchoalveolar lavage ( BAL ) cells</cell_type> appeared to decrease significantly ."}
{"id": "3179", "text": "In contrast , neither PMNs nor AMs changed substantially 1 h after NaVO3 instillation .", "annotated_text": "In contrast , neither <cell_type>PMNs</cell_type> nor <cell_type>AMs</cell_type> changed substantially 1 h after NaVO3 instillation ."}
{"id": "3180", "text": "By Northern analysis , macrophage inflammatory protein ( MIP ) -2 mRNA in BAL cells increased markedly 1 h after NaVO3 instillation and reduced a little bit at 4 h , whereas MIP-1alpha mRNA in BAL cells was expressed relatively high 1 h after NaVO3 instillation , although a basal expression was detected in control group , and returned rapidly nearly to control level at 4 h .", "annotated_text": "By Northern analysis , <rna>macrophage inflammatory protein ( MIP ) -2 mRNA</rna> in <cell_type>BAL cells</cell_type> increased markedly 1 h after NaVO3 instillation and reduced a little bit at 4 h , whereas <rna>MIP-1alpha mRNA</rna> in <cell_type>BAL cells</cell_type> was expressed relatively high 1 h after NaVO3 instillation , although a basal expression was detected in control group , and returned rapidly nearly to control level at 4 h ."}
{"id": "3181", "text": "Since MIP-2 is a potent PMN chemoattractant and MIP-1alpha is a potent macrophage/monocyte chemoattractant has been well known .", "annotated_text": "Since <protein>MIP-2</protein> is a potent <cell_type>PMN</cell_type> chemoattractant and <protein>MIP-1alpha</protein> is a potent macrophage/monocyte chemoattractant has been well known ."}
{"id": "3182", "text": "The facts that PMN influx was preceded by increased MIP-2 mRNA expression , suggesting that MIP-2 is involved in the development of NaVO3-induced pulmonary inflammation , whereas increased MIP-1alpha mRNA expression was followed by decreased AMs in BAL cells , suggesting AMs might be activated by MIP-1alpha , adherent to the lining surface of the airways and then resistant to be washed out .", "annotated_text": "The facts that <cell_type>PMN</cell_type> influx was preceded by increased MIP-2 mRNA expression , suggesting that <protein>MIP-2</protein> is involved in the development of NaVO3-induced pulmonary inflammation , whereas increased <rna>MIP-1alpha mRNA</rna> expression was followed by decreased <cell_type>AMs</cell_type> in <cell_type>BAL cells</cell_type> , suggesting <cell_type>AMs</cell_type> might be activated by <protein>MIP-1alpha</protein> , adherent to the lining surface of the airways and then resistant to be washed out ."}
{"id": "3183", "text": "To delineate the mechanisms of transcriptional activation , we recently cloned the 5'-flanking region of the MIP-2 gene .", "annotated_text": "To delineate the mechanisms of transcriptional activation , we recently cloned the <dna>5'-flanking region</dna> of the <dna>MIP-2 gene</dna> ."}
{"id": "3184", "text": "The promotor region contains consensus binding sites for transcription factor nuclear factor kappaB ( NF-kappaB ) and activator protein-1 ( AP-1 ) .", "annotated_text": "The <dna>promotor region</dna> contains <dna>consensus binding sites</dna> for <protein>transcription factor nuclear factor kappaB</protein> ( <protein>NF-kappaB</protein> ) and <protein>activator protein-1</protein> ( <protein>AP-1</protein> ) ."}
{"id": "3185", "text": "Using electrophoretic mobility shift assay , increased nuclear NF-kappaB , not AP-1 , binding activity was detected 1 h after NaVO3 instillation , which correlated with the induction of MIP-2 mRNA .", "annotated_text": "Using electrophoretic mobility shift assay , increased nuclear <protein>NF-kappaB</protein> , not <protein>AP-1</protein> , binding activity was detected 1 h after NaVO3 instillation , which correlated with the induction of <rna>MIP-2 mRNA</rna> ."}
{"id": "3186", "text": "p65 ( Rel A ) and p50 protein appears to be involved in MIP-2 NF-kappaB binding .", "annotated_text": "<protein>p65 ( Rel A )</protein> and <protein>p50 protein</protein> appears to be involved in MIP-2 <protein>NF-kappaB</protein> binding ."}
{"id": "3187", "text": "Taken together , our studies suggest that MIP-2 is an important mediator of NaVO3-induced pulmonary inflammation in the rat model .", "annotated_text": "Taken together , our studies suggest that <protein>MIP-2</protein> is an important mediator of NaVO3-induced pulmonary inflammation in the rat model ."}
{"id": "3188", "text": "In addition , elevated MIP-2 mRNA levels are accompanied by increased NF-kappaB binding activity in BAL cells , suggesting possible MIP-2 transcriptional regulation through NF-kappaB .", "annotated_text": "In addition , elevated <rna>MIP-2 mRNA</rna> levels are accompanied by increased <protein>NF-kappaB</protein> binding activity in <cell_type>BAL cells</cell_type> , suggesting possible <protein>MIP-2</protein> transcriptional regulation through <protein>NF-kappaB</protein> ."}
{"id": "3189", "text": "Activation of signal transduction and apoptosis in healthy lymphomonocytes exposed to bystander HIV-1-infected cells .", "annotated_text": "Activation of signal transduction and apoptosis in <cell_type>healthy lymphomonocytes</cell_type> exposed to bystander <cell_type>HIV-1-infected cells</cell_type> ."}
{"id": "3190", "text": "Persistent activation of the immune system is one of the hallmarks of HIV-1 infection .", "annotated_text": "Persistent activation of the immune system is one of the hallmarks of HIV-1 infection ."}
{"id": "3191", "text": "In this study we analysed the induction of factors involved in cytokine signal transduction , such as STAT 1 proteins and IRF-1 mRNA , in normal peripheral blood mononuclear cells ( PBMC ) exposed to HIV-infected cells , and the induction of apoptosis .", "annotated_text": "In this study we analysed the induction of factors involved in cytokine signal transduction , such as <protein>STAT 1 proteins</protein> and <rna>IRF-1 mRNA</rna> , in <cell_type>normal peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) exposed to <cell_type>HIV-infected cells</cell_type> , and the induction of apoptosis ."}
{"id": "3192", "text": "Western blot analyses and reverse transcriptase-polymerase chain reaction results indicate that both cells infected with a X4 strain and cells infected with a R5 strain are able to increase intracellular levels of STAT 1alpha and beta proteins as well as IRF-1 mRNA .", "annotated_text": "Western blot analyses and reverse transcriptase-polymerase chain reaction results indicate that both cells infected with a X4 strain and cells infected with a R5 strain are able to increase intracellular levels of <protein>STAT 1alpha and beta</protein> proteins as well as <rna>IRF-1 mRNA</rna> ."}
{"id": "3193", "text": "This effect was prevented by neutralizing antibodies against interferon-alpha ( IFN-alpha ) .", "annotated_text": "This effect was prevented by neutralizing antibodies against <protein>interferon-alpha</protein> ( <protein>IFN-alpha</protein> ) ."}
{"id": "3194", "text": "HIV-1-infected cells dose-dependently induced apoptotic commitment in normal PBMC , as revealed by DNA fragmentation analysis , but this was not accompanied by an increase of caspase-3 activity , even if a slight up-regulation of IL-1beta-converting enzyme mRNA was detected .", "annotated_text": "<cell_type>HIV-1-infected cells</cell_type> dose-dependently induced apoptotic commitment in <cell_type>normal PBMC</cell_type> , as revealed by DNA fragmentation analysis , but this was not accompanied by an increase of caspase-3 activity , even if a slight up-regulation of <rna>IL-1beta-converting enzyme mRNA</rna> was detected ."}
{"id": "3195", "text": "Apoptosis induction could be abrogated mainly by antibodies against tumour necrosis factor-alpha ( TNF-alpha ) and , to a lesser extent , by antibodies against IFN-gamma .", "annotated_text": "Apoptosis induction could be abrogated mainly by <protein>antibodies</protein> against <protein>tumour necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) and , to a lesser extent , by <protein>antibodies</protein> against <protein>IFN-gamma</protein> ."}
{"id": "3196", "text": "All these findings suggest that uninfected PBMC can undergo activation of signal transduction and apoptosis after exposure to bystander HIV-infected cells , subsequent to the induction of cytokines such as IFNs and TNF-alpha .", "annotated_text": "All these findings suggest that <cell_type>uninfected PBMC</cell_type> can undergo activation of signal transduction and apoptosis after exposure to bystander <cell_type>HIV-infected cells</cell_type> , subsequent to the induction of <protein>cytokines</protein> such as <protein>IFNs</protein> and <protein>TNF-alpha</protein> ."}
{"id": "3197", "text": "The physical association of protein kinase C theta with a lipid raft-associated inhibitor of kappa B factor kinase ( IKK ) complex plays a role in the activation of the NF-kappa B cascade by TCR and CD28 .", "annotated_text": "The physical association of <protein>protein kinase C theta</protein> with a lipid raft-associated inhibitor of <protein>kappa B factor kinase ( IKK ) complex</protein> plays a role in the activation of the NF-kappa B cascade by <protein>TCR</protein> and <protein>CD28</protein> ."}
{"id": "3198", "text": "We investigated the role of protein kinase C theta ( PKCtheta ) in the activation of the NF-kappaB cascade in primary human CD4 ( + ) lymphocytes .", "annotated_text": "We investigated the role of <protein>protein kinase C theta</protein> ( <protein>PKCtheta</protein> ) in the activation of the <protein>NF-kappaB</protein> cascade in <cell_type>primary human CD4 ( + ) lymphocytes</cell_type> ."}
{"id": "3199", "text": "Among six or so PKC isoforms expressed in T cells , only PKCtheta participates in the assembly of the supramolecular activation clusters at the contact site of the TCR with Ag .", "annotated_text": "Among six or so <protein>PKC isoforms</protein> expressed in <cell_type>T cells</cell_type> , only <protein>PKCtheta</protein> participates in the assembly of the supramolecular activation clusters at the contact site of the <protein>TCR</protein> with <protein>Ag</protein> ."}
{"id": "3200", "text": "Signaling via both the TCR and CD28 is required for optimal activation of the multisubunit IkappaB kinase ( IKK ) complex in primary human T lymphocytes ; this activation could be inhibited by a Ca ( 2+ ) -independent PKC isoform inhibitor , rottlerin .", "annotated_text": "Signaling via both the <protein>TCR</protein> and <protein>CD28</protein> is required for optimal activation of the <protein>multisubunit IkappaB kinase ( IKK ) complex</protein> in <cell_type>primary human T lymphocytes</cell_type> ; this activation could be inhibited by a Ca ( 2+ ) -independent PKC isoform inhibitor , rottlerin ."}
{"id": "3201", "text": "Moreover , endogenous PKCtheta physically associates with activated IKK complexes in CD3/CD28-costimulated primary CD4 ( + ) T cells .", "annotated_text": "Moreover , endogenous <protein>PKCtheta</protein> physically associates with activated <protein>IKK complexes</protein> in <cell_type>CD3/CD28-costimulated primary CD4 ( + ) T cells</cell_type> ."}
{"id": "3202", "text": "The same set of stimuli also induced relocation of endogenous PKCtheta and IKKs to a GM1 ganglioside-enriched , detergent-insoluble membrane compartment in primary T cells .", "annotated_text": "The same set of stimuli also induced relocation of endogenous <protein>PKCtheta</protein> and <protein>IKKs</protein> to a GM1 ganglioside-enriched , detergent-insoluble membrane compartment in <cell_type>primary T cells</cell_type> ."}
{"id": "3203", "text": "IKKs recruited to these lipid rafts were capable of phosphorylating a recombinant IkappaBalpha sustrate .", "annotated_text": "<protein>IKKs</protein> recruited to these lipid rafts were capable of phosphorylating a recombinant IkappaBalpha sustrate ."}
{"id": "3204", "text": "Confocal microscopy further demonstrated that exogenously expressed PKCtheta and IKKss colocalize in the membrane of CD3/CD28-costimulated Jurkat T cells .", "annotated_text": "Confocal microscopy further demonstrated that exogenously expressed <protein>PKCtheta</protein> and <protein>IKKss</protein> colocalize in the membrane of <cell_line>CD3/CD28-costimulated Jurkat T cells</cell_line> ."}
{"id": "3205", "text": "Constitutively active but not kinase-inactive PKCtheta activated IKKbeta in Jurkat T cells .", "annotated_text": "Constitutively active but not <protein>kinase-inactive PKCtheta</protein> activated <protein>IKKbeta</protein> in <cell_line>Jurkat T cells</cell_line> ."}
{"id": "3206", "text": "Expression of dominant-active PKCtheta also had stimulatory effects on the CD28 response element of the IL-2 promoter .", "annotated_text": "Expression of <protein>dominant-active PKCtheta</protein> also had stimulatory effects on the <dna>CD28 response element</dna> of the <dna>IL-2 promoter</dna> ."}
{"id": "3207", "text": "Taken together , these data show that the activation of PKCtheta by the TCR and CD28 plays an important role in the assembly and activation of IKK complexes in the T cell membrane", "annotated_text": "Taken together , these data show that the activation of <protein>PKCtheta</protein> by the <protein>TCR</protein> and <protein>CD28</protein> plays an important role in the assembly and activation of <protein>IKK complexes</protein> in the T cell membrane"}
{"id": "3208", "text": "T-cell -mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma .", "annotated_text": "<cell_type>T-cell</cell_type> -mediated regulation of osteoclastogenesis by signalling cross-talk between <protein>RANKL</protein> and <protein>IFN-gamma</protein> ."}
{"id": "3209", "text": "Bone resorption is regulated by the immune system , where T-cell expression of RANKL ( receptor activator of nuclear factor ( NF ) -kappaB ligand ) , a member of the tumour-necrosis factor family that is essential for osteoclastogenesis , may contribute to pathological conditions , such as autoimmune arthritis .", "annotated_text": "Bone resorption is regulated by the immune system , where <cell_type>T-cell</cell_type> expression of <protein>RANKL</protein> ( <protein>receptor activator of nuclear factor ( NF ) -kappaB ligand</protein> ) , a member of the <protein>tumour-necrosis factor family</protein> that is essential for osteoclastogenesis , may contribute to pathological conditions , such as autoimmune arthritis ."}
{"id": "3210", "text": "However , whether activated T cells maintain bone homeostasis by counterbalancing the action of RANKL remains unknown .", "annotated_text": "However , whether <cell_type>activated T cells</cell_type> maintain bone homeostasis by counterbalancing the action of <protein>RANKL</protein> remains unknown ."}
{"id": "3211", "text": "Here we show that T-cell production of interferon ( IFN ) -gamma strongly suppresses osteoclastogenesis by interfering with the RANKL -RANK signalling pathway .", "annotated_text": "Here we show that <cell_type>T-cell</cell_type> production of <protein>interferon ( IFN ) -gamma</protein> strongly suppresses osteoclastogenesis by interfering with the <protein>RANKL</protein> -RANK signalling pathway ."}
{"id": "3212", "text": "IFN-gamma induces rapid degradation of the RANK adapter protein , TRAF6 ( tumour necrosis factor receptor-associated factor 6 ) , which results in strong inhibition of the RANKL -induced activation of the transcription factor NF-kappaB and JNK .", "annotated_text": "<protein>IFN-gamma</protein> induces rapid degradation of the <protein>RANK adapter protein</protein> , <protein>TRAF6</protein> ( <protein>tumour necrosis factor receptor-associated factor 6</protein> ) , which results in strong inhibition of the <protein>RANKL</protein> -induced activation of the <protein>transcription factor</protein> <protein>NF-kappaB</protein> and <protein>JNK</protein> ."}
{"id": "3213", "text": "This inhibition of osteoclastogenesis is rescued by overexpressing TRAF6 in precursor cells , which indicates that TRAF6 is the target critical for the IFN-gamma action .", "annotated_text": "This inhibition of osteoclastogenesis is rescued by overexpressing <protein>TRAF6</protein> in <cell_type>precursor cells</cell_type> , which indicates that <protein>TRAF6</protein> is the target critical for the <protein>IFN-gamma</protein> action ."}
{"id": "3214", "text": "Furthermore , we provide evidence that the accelerated degradation of TRAF6 requires both its ubiquitination , which is initiated by RANKL , and IFN-gamma -induced activation of the ubiquitin-proteasome system .", "annotated_text": "Furthermore , we provide evidence that the accelerated degradation of <protein>TRAF6</protein> requires both its ubiquitination , which is initiated by <protein>RANKL</protein> , and <protein>IFN-gamma</protein> -induced activation of the ubiquitin-proteasome system ."}
{"id": "3215", "text": "Our study shows that there is cross-talk between the tumour necrosis factor and IFN families of cytokines , through which IFN-gamma provides a negative link between T-cell activation and bone resorption .", "annotated_text": "Our study shows that there is cross-talk between the <protein>tumour necrosis factor</protein> and <protein>IFN families</protein> of <protein>cytokines</protein> , through which <protein>IFN-gamma</protein> provides a negative link between <cell_type>T-cell</cell_type> activation and bone resorption ."}
{"id": "3216", "text": "Our results may offer a therapeutic approach to treat the inflammation-induced tissue breakdown .", "annotated_text": "Our results may offer a therapeutic approach to treat the inflammation-induced tissue breakdown ."}
{"id": "3217", "text": "Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of human megakaryopoiesis .", "annotated_text": "<protein>Stromal-derived factor 1</protein> and <protein>thrombopoietin</protein> regulate distinct aspects of human megakaryopoiesis ."}
{"id": "3218", "text": "The role of the chemokine binding stromal-derived factor 1 ( SDF-1 ) in normal human megakaryopoiesis at the cellular and molecular levels and its comparison with that of thrombopoietin ( TPO ) have not been determined .", "annotated_text": "The role of the <protein>chemokine</protein> binding <protein>stromal-derived factor 1</protein> ( <protein>SDF-1</protein> ) in normal human megakaryopoiesis at the cellular and molecular levels and its comparison with that of <protein>thrombopoietin</protein> ( <protein>TPO</protein> ) have not been determined ."}
{"id": "3219", "text": "In this study it was found that SDF-1 , unlike TPO , does not stimulate alpha ( IIb ) beta ( 3 ) ( + ) cell proliferation or differentiation or have an antiapoptotic effect .", "annotated_text": "In this study it was found that <protein>SDF-1</protein> , unlike <protein>TPO</protein> , does not stimulate alpha ( IIb ) beta ( 3 ) ( + ) cell proliferation or differentiation or have an antiapoptotic effect ."}
{"id": "3220", "text": "However , it does induce chemotaxis , trans-Matrigel migration , and secretion of matrix metalloproteinase 9 ( MMP-9 ) and vascular endothelial growth factor ( VEGF ) by these cells , and both SDF-1 and TPO increase the adhesion of alpha ( IIb ) beta ( 3 ) ( + ) cells to fibrinogen and vitronectin .", "annotated_text": "However , it does induce chemotaxis , trans-Matrigel migration , and secretion of matrix <protein>metalloproteinase 9</protein> ( <protein>MMP-9</protein> ) and <protein>vascular endothelial growth factor</protein> ( <protein>VEGF</protein> ) by these cells , and both <protein>SDF-1</protein> and <protein>TPO</protein> increase the adhesion of <cell_type>alpha ( IIb ) beta ( 3 ) ( + ) cells</cell_type> to <protein>fibrinogen</protein> and <protein>vitronectin</protein> ."}
{"id": "3221", "text": "Investigating the intracellular signaling pathways induced by SDF-1 and TPO revealed some overlapping patterns of protein phosphorylation/activation ( mitogen-activated protein kinase [ MAPK ] p42/44 , MAPK p38 , and AKT [ protein kinase B ] ) and some that were distinct for TPO ( eg , JAK-STAT ) and for SDF-1 ( eg , NF-kappa B ) .", "annotated_text": "Investigating the intracellular signaling pathways induced by <protein>SDF-1</protein> and <protein>TPO</protein> revealed some overlapping patterns of protein phosphorylation/activation ( <protein>mitogen-activated protein kinase [ MAPK ] p42/44</protein> , <protein>MAPK p38</protein> , and <protein>AKT [ protein kinase B ]</protein> ) and some that were distinct for <protein>TPO</protein> ( eg , <protein>JAK-STAT</protein> ) and for <protein>SDF-1</protein> ( eg , <protein>NF-kappa B</protein> ) ."}
{"id": "3222", "text": "It was also found that though inhibition of phosphatidyl-inositol 3-kinase ( PI-3K ) by LY294002 in alpha ( IIb ) beta ( 3 ) ( + ) cells induced apoptosis and inhibited chemotaxis adhesion and the secretion of MMP-9 and VEGF , the inhibition of MAPK p42/44 ( by the MEK inhibitor U0126 ) had no effect on the survival , proliferation , and migration of these cells .", "annotated_text": "It was also found that though inhibition of <protein>phosphatidyl-inositol 3-kinase</protein> ( <protein>PI-3K</protein> ) by LY294002 in <cell_type>alpha ( IIb ) beta ( 3 ) ( + ) cells</cell_type> induced apoptosis and inhibited chemotaxis adhesion and the secretion of <protein>MMP-9</protein> and <protein>VEGF</protein> , the inhibition of <protein>MAPK p42/44</protein> ( by the MEK inhibitor U0126 ) had no effect on the survival , proliferation , and migration of these cells ."}
{"id": "3223", "text": "Hence , it is suggested that the proliferative effect of TPO is more related to activation of the JAK-STAT pathway ( unique to TPO ) , and the PI-3K-AKT axis is differentially involved in TPO- and SDF-1-dependent signaling .", "annotated_text": "Hence , it is suggested that the proliferative effect of <protein>TPO</protein> is more related to activation of the JAK-STAT pathway ( unique to <protein>TPO</protein> ) , and the PI-3K-AKT axis is differentially involved in TPO- and SDF-1-dependent signaling ."}
{"id": "3224", "text": "Accordingly , PI-3K is involved in TPO -mediated inhibition of apoptosis , TPO- and SDF-1-regulated adhesion to fibrinogen and vitronectin , and SDF-1 -mediated migration .", "annotated_text": "Accordingly , <protein>PI-3K</protein> is involved in <protein>TPO</protein> -mediated inhibition of apoptosis , TPO- and SDF-1-regulated adhesion to <protein>fibrinogen</protein> and <protein>vitronectin</protein> , and <protein>SDF-1</protein> -mediated migration ."}
{"id": "3225", "text": "This study expands the understanding of the role of SDF-1 and TPO in normal human megakaryopoiesis and indicates the molecular basis of the observed differences in cellular responses .", "annotated_text": "This study expands the understanding of the role of <protein>SDF-1</protein> and <protein>TPO</protein> in normal human megakaryopoiesis and indicates the molecular basis of the observed differences in cellular responses ."}
{"id": "3226", "text": "( Blood. 2000 ; 96 : 4142-4151 )", "annotated_text": "( Blood. 2000 ; 96 : 4142-4151 )"}
{"id": "3227", "text": "Adhesion of immature and mature T cells induces in human thymic epithelial cells ( TEC ) activation of IL-6 gene trascription factors ( NF-kappaB and NF-IL6 ) and IL-6 gene expression : role of alpha3beta1 and alpha6beta4 integrins .", "annotated_text": "Adhesion of <cell_type>immature and mature T cells</cell_type> induces in <cell_type>human thymic epithelial cells</cell_type> ( <cell_type>TEC</cell_type> ) activation of <protein>IL-6 gene trascription factors</protein> ( <protein>NF-kappaB</protein> and <protein>NF-IL6</protein> ) and IL-6 gene expression : role of <protein>alpha3beta1 and alpha6beta4 integrins</protein> ."}
{"id": "3228", "text": "T cell precursors homed to thymus develop in close contact with stromal cells .", "annotated_text": "<cell_type>T cell precursors</cell_type> homed to thymus develop in close contact with <cell_type>stromal cells</cell_type> ."}
{"id": "3229", "text": "Among them , thymic epithelial cells ( TEC ) are known to exert dominant roles in their survival and functional shaping .", "annotated_text": "Among them , <cell_type>thymic epithelial cells</cell_type> ( <cell_type>TEC</cell_type> ) are known to exert dominant roles in their survival and functional shaping ."}
{"id": "3230", "text": "Key molecules mediating TEC / thymocytes interactions include cytokines and growth factors secreted by the two cell types and adhesion receptors mediating cell contact .", "annotated_text": "Key molecules mediating <cell_type>TEC</cell_type> / <cell_type>thymocytes</cell_type> interactions include <protein>cytokines</protein> and <protein>growth factors</protein> secreted by the two cell types and <protein>adhesion receptors</protein> mediating cell contact ."}
{"id": "3231", "text": "Signaling events triggered in thymocytes by adhesion to epithelial cells have been extensively investigated , whereas little is known on the opposite phenomenon .", "annotated_text": "Signaling events triggered in <cell_type>thymocytes</cell_type> by adhesion to <cell_type>epithelial cells</cell_type> have been extensively investigated , whereas little is known on the opposite phenomenon ."}
{"id": "3232", "text": "We have previously investigated this issue in a co-culture system composed of TEC cultures derived from human normal thymus and heterologous thymocytes .", "annotated_text": "We have previously investigated this issue in a co-culture system composed of <cell_type>TEC cultures</cell_type> derived from human normal thymus and <cell_type>heterologous thymocytes</cell_type> ."}
{"id": "3233", "text": "We demonstrated that thymocytes adhere to TEC involving beta1 and beta4 integrins and induce the clustering of alpha3beta1 and alpha6beta4 heterodimers at the TEC surface .", "annotated_text": "We demonstrated that <cell_type>thymocytes</cell_type> adhere to <cell_type>TEC</cell_type> involving <protein>beta1 and beta4 integrins</protein> and induce the clustering of <protein>alpha3beta1 and alpha6beta4 heterodimers</protein> at the TEC surface ."}
{"id": "3234", "text": "In addition thymocyte adhesion was followed by activation of NF-kappaB and NF-IL6 gene transcription factors and enhanced IL-6 production .", "annotated_text": "In addition thymocyte adhesion was followed by activation of <protein>NF-kappaB</protein> and <protein>NF-IL6</protein> <protein>gene transcription factors</protein> and enhanced IL-6 production ."}
{"id": "3235", "text": "The two latter phenomena were reproduced by the cross-linking of the alpha3 , alpha6 , beta1 and beta4 integrins , thus implying that the alpha3beta1 and alpha6beta4 heterodimers can signal during thymocyte adhesion .", "annotated_text": "The two latter phenomena were reproduced by the cross-linking of the <protein>alpha3</protein> , <protein>alpha6</protein> , <protein>beta1 and beta4 integrins</protein> , thus implying that the <protein>alpha3beta1 and alpha6beta4 heterodimers</protein> can signal during thymocyte adhesion ."}
{"id": "3236", "text": "We have extended our previous work investigating in the same experimental setting the inducing activity of non stimulated or activated policlonal or clonal mature T cells as representative of the more mature thymocyte subset .", "annotated_text": "We have extended our previous work investigating in the same experimental setting the inducing activity of non stimulated or activated <cell_type>policlonal or clonal mature T cells</cell_type> as representative of the more <cell_type>mature thymocyte subset</cell_type> ."}
{"id": "3237", "text": "We found that adhesion of unstimulated T cell i ) involved beta1 , but not beta4 integrin functions at the surface ii ) induced the clustering of alpha3beta1 , but not alpha2beta1 heterodimers at the TEC surface and iii ) up-regulated the nuclear binding activity of NF-kappaB transcription factor and the IL-6 secretion .", "annotated_text": "We found that adhesion of <cell_type>unstimulated T cell</cell_type> i ) involved beta1 , but not beta4 integrin functions at the surface ii ) induced the clustering of <protein>alpha3beta1</protein> , but not <protein>alpha2beta1 heterodimers</protein> at the TEC surface and iii ) up-regulated the nuclear binding activity of <protein>NF-kappaB transcription factor</protein> and the IL-6 secretion ."}
{"id": "3238", "text": "We propose that alpha3beta1 and alpha6beta4 heterodimers are induced to cluster at the TEC surface recognizing yet unknown cellular ligands differentially expressed during T cell development .", "annotated_text": "We propose that <protein>alpha3beta1 and alpha6beta4 heterodimers</protein> are induced to cluster at the TEC surface recognizing yet unknown <protein>cellular ligands</protein> differentially expressed during T cell development ."}
{"id": "3239", "text": "Identification and characterization of SKAT-2 , a novel Th2-specific zinc finger gene .", "annotated_text": "Identification and characterization of <dna>SKAT-2</dna> , a novel <dna>Th2-specific zinc finger gene</dna> ."}
{"id": "3240", "text": "We have identified a novel Kruppel-type zinc finger ( ZF ) gene , SKAT-2 , which is selectively expressed by murine Th2 cells .", "annotated_text": "We have identified a novel <dna>Kruppel-type zinc finger ( ZF ) gene</dna> , <dna>SKAT-2</dna> , which is selectively expressed by <cell_type>murine Th2 cells</cell_type> ."}
{"id": "3241", "text": "The protein encoded by this gene has 14 C2H2-type ZF tandemly arrayed at its C terminus and N-terminal SCAN box and KRAB domains .", "annotated_text": "The protein encoded by this gene has 14 C2H2-type ZF tandemly arrayed at its <dna>C terminus</dna> and <dna>N-terminal</dna> <dna>SCAN box</dna> and <dna>KRAB domains</dna> ."}
{"id": "3242", "text": "SKAT-2 is tissue restricted in expression at the RNA level , detectable only in brain and at low levels in kidney and spleen and few hematopoietic cell lines .", "annotated_text": "<dna>SKAT-2</dna> is tissue restricted in expression at the RNA level , detectable only in brain and at low levels in kidney and spleen and few <cell_line>hematopoietic cell lines</cell_line> ."}
{"id": "3243", "text": "By in situ hybridization , SKAT-2 expression was found to peak in antigen-stimulated CD4 ( + ) T cells after 2-3 days of culture under Th2 but not Th1 biasing conditions .", "annotated_text": "By in situ hybridization , <dna>SKAT-2</dna> expression was found to peak in antigen-stimulated <cell_type>CD4 ( + ) T cells</cell_type> after 2-3 days of culture under Th2 but not Th1 biasing conditions ."}
{"id": "3244", "text": "This pattern of expression closely mirrored that of GATA-3 in the same cells .", "annotated_text": "This pattern of expression closely mirrored that of <protein>GATA-3</protein> in the same cells ."}
{"id": "3245", "text": "In transient transfection experiments in phorbol 12-myristate 13-acetate/ionomycin-stimulated EL4 cells , SKAT-2 was found to up-regulate the activity of the IL-4 but not the IL-5 promoter , contrasting with the ability of GATA-3 to activate both promoters .", "annotated_text": "In transient transfection experiments in phorbol 12-myristate 13-acetate/ionomycin-stimulated <cell_line>EL4 cells</cell_line> , <dna>SKAT-2</dna> was found to up-regulate the activity of the <dna>IL-4 but not the IL-5 promoter</dna> , contrasting with the ability of <protein>GATA-3</protein> to activate both <dna>promoters</dna> ."}
{"id": "3246", "text": "This result was confirmed using clones of EL4 cells stably expressing an inducible form of SKAT-2 , thus SKAT-2 is a novel Th2-specific gene that may play a role in selective regulation of cytokine genes in T cells .", "annotated_text": "This result was confirmed using clones of <cell_line>EL4 cells</cell_line> stably expressing an inducible form of <dna>SKAT-2</dna> , thus <dna>SKAT-2</dna> is a novel <dna>Th2-specific gene</dna> that may play a role in selective regulation of <dna>cytokine genes</dna> in <cell_type>T cells</cell_type> ."}
{"id": "3247", "text": "hsp70 interacting protein Hip does not affect glucocorticoid receptor folding by the hsp90-based chaperone machinery except to oppose the effect of BAG-1 .", "annotated_text": "<protein>hsp70 interacting protein Hip</protein> does not affect <protein>glucocorticoid receptor</protein> folding by the hsp90-based chaperone machinery except to oppose the effect of <protein>BAG-1</protein> ."}
{"id": "3248", "text": "Reticulocyte lysate contains a chaperone system that assembles glucocorticoid receptor ( GR ) .hsp90 heterocomplexes .", "annotated_text": "Reticulocyte lysate contains a chaperone system that assembles <protein>glucocorticoid receptor ( GR ) .hsp90 heterocomplexes</protein> ."}
{"id": "3249", "text": "Using purified proteins , we have prepared a five-protein heterocomplex assembly system consisting of two proteins essential for heterocomplex assembly- hsp90 and hsp70 -and three proteins that act as co-chaperones to enhance assembly- Hop , hsp40 , p23 [ Morishima , Y. , Kanelakis , K. C. , Silverstein , A. M. , Dittmar , K. D. , Estrada , L. , and Pratt , W. B. ( 2000 ) J. Biol. Chem. 275 , 6894-6900 ] .", "annotated_text": "Using <protein>purified proteins</protein> , we have prepared a five-protein heterocomplex assembly system consisting of two proteins essential for heterocomplex assembly- <protein>hsp90</protein> and <protein>hsp70</protein> -and three proteins that act as co-chaperones to enhance assembly- <protein>Hop</protein> , <protein>hsp40</protein> , <protein>p23</protein> [ Morishima , Y. , Kanelakis , K. C. , Silverstein , A. M. , Dittmar , K. D. , Estrada , L. , and Pratt , W. B. ( 2000 ) J. Biol. Chem. 275 , 6894-6900 ] ."}
{"id": "3250", "text": "The hsp70 co-chaperone Hip has been recovered in receptor.hsp90 heterocomplexes at an intermediate stage of assembly in reticulocyte lysate , and Hip is also thought to be an intrinsic component of the assembly machinery .", "annotated_text": "The <protein>hsp70 co-chaperone Hip</protein> has been recovered in <protein>receptor.hsp90 heterocomplexes</protein> at an intermediate stage of assembly in reticulocyte lysate , and <protein>Hip</protein> is also thought to be an intrinsic component of the assembly machinery ."}
{"id": "3251", "text": "Here we show that immunodepletion of Hip from reticulocyte lysate or addition of high levels of Hip to the purified five-protein system does not affect GR.hsp90 heterocomplex assembly or the activation of steroid binding activity that occurs with assembly .", "annotated_text": "Here we show that immunodepletion of <protein>Hip</protein> from reticulocyte lysate or addition of high levels of <protein>Hip</protein> to the purified five-protein system does not affect GR.hsp90 heterocomplex assembly or the activation of steroid binding activity that occurs with assembly ."}
{"id": "3252", "text": "Despite the fact that Hip does not affect assembly , it is recovered in GR.hsp90 heterocomplexes assembled by both systems .", "annotated_text": "Despite the fact that <protein>Hip</protein> does not affect assembly , it is recovered in <protein>GR.hsp90 heterocomplexes</protein> assembled by both systems ."}
{"id": "3253", "text": "In the five-protein system , Hip prevents inhibition of assembly by the hsp70 co-chaperone BAG-1 , and cotransfection of Hip with BAG-1 opposes BAG-1 reduction of steroid binding activity in COS cells .", "annotated_text": "In the five-protein system , <protein>Hip</protein> prevents inhibition of assembly by the <protein>hsp70 co-chaperone BAG-1</protein> , and cotransfection of <protein>Hip</protein> with <protein>BAG-1</protein> opposes <protein>BAG-1</protein> reduction of steroid binding activity in <cell_line>COS cells</cell_line> ."}
{"id": "3254", "text": "We conclude that Hip is not a component of the assembly machinery but that it could play a regulatory role in opposition to BAG-1 .", "annotated_text": "We conclude that <protein>Hip</protein> is not a component of the assembly machinery but that it could play a regulatory role in opposition to <protein>BAG-1</protein> ."}
{"id": "3255", "text": "Cutting edge : STAT6-deficient mice have enhanced tumor immunity to primary and metastatic mammary carcinoma .", "annotated_text": "Cutting edge : STAT6-deficient mice have enhanced tumor immunity to primary and metastatic mammary carcinoma ."}
{"id": "3256", "text": "STAT4 and STAT6 are essential for the development of CD4 ( + ) Th1 and Th2 development , respectively .", "annotated_text": "<protein>STAT4</protein> and <protein>STAT6</protein> are essential for the development of CD4 ( + ) Th1 and Th2 development , respectively ."}
{"id": "3257", "text": "Tumor immunologists have hypothesized that Th1 cells are critical in tumor immunity because they facilitate differentiation of CD8 ( + ) T cells , which are potent anti-tumor effectors .", "annotated_text": "Tumor immunologists have hypothesized that <cell_type>Th1 cells</cell_type> are critical in tumor immunity because they facilitate differentiation of <cell_type>CD8 ( + ) T cells</cell_type> , which are potent <cell_type>anti-tumor effectors</cell_type> ."}
{"id": "3258", "text": "We have used STAT4 ( -/- ) and STAT6 ( -/- ) mice to test this hypothesis .", "annotated_text": "We have used STAT4 ( -/- ) and STAT6 ( -/- ) mice to test this hypothesis ."}
{"id": "3259", "text": "BALB/c and knockout mice were challenged in the mammary gland with the highly malignant and spontaneously metastatic BALB/c-derived 4T1 mammary carcinoma .", "annotated_text": "BALB/c and knockout mice were challenged in the mammary gland with the highly malignant and spontaneously metastatic BALB/c-derived 4T1 mammary carcinoma ."}
{"id": "3260", "text": "Primary tumor growth and metastatic disease are reduced in STAT6 ( -/- ) mice relative to BALB/c and STAT4 ( -/- ) mice .", "annotated_text": "Primary tumor growth and metastatic disease are reduced in STAT6 ( -/- ) mice relative to BALB/c and STAT4 ( -/- ) mice ."}
{"id": "3261", "text": "Ab depletions demonstrate that the effect is mediated by CD8 ( + ) T cells , and immunized STAT6 ( -/- ) mice have higher levels of 4T1-specific CTL than BALB/c or STAT4 ( -/- ) mice .", "annotated_text": "Ab depletions demonstrate that the effect is mediated by <cell_type>CD8 ( + ) T cells</cell_type> , and immunized STAT6 ( -/- ) mice have higher levels of <cell_type>4T1-specific CTL</cell_type> than BALB/c or STAT4 ( -/- ) mice ."}
{"id": "3262", "text": "Surprisingly , Th1 or Th2 cells are not involved , because CD4 depletion does not diminish the anti-tumor effect .", "annotated_text": "Surprisingly , <cell_type>Th1 or Th2 cells</cell_type> are not involved , because CD4 depletion does not diminish the anti-tumor effect ."}
{"id": "3263", "text": "Therefore , deletion of the STAT6 gene facilitates development of potent anti-tumor immunity via a CD4 ( + ) -independent pathway .", "annotated_text": "Therefore , deletion of the <dna>STAT6 gene</dna> facilitates development of potent anti-tumor immunity via a CD4 ( + ) -independent pathway ."}
{"id": "3264", "text": "Activation of oncogenic transcription factor AP-1 in T cells infected with human T cell leukemia virus type 1 .", "annotated_text": "Activation of <protein>oncogenic transcription factor AP-1</protein> in <cell_type>T cells</cell_type> infected with human T cell leukemia virus type 1 ."}
{"id": "3265", "text": "Human T cell leukemia virus type 1 ( HTLV-1 ) Tax protein transforms primary human T cells in vitro .", "annotated_text": "Human T cell leukemia virus type 1 ( HTLV-1 ) <protein>Tax protein</protein> transforms <cell_type>primary human T cells</cell_type> in vitro ."}
{"id": "3266", "text": "We previously showed that Tax induces the expression of various family members of the transcription factor AP-1 such as c-Jun , JunD , c-Fos , and Fra-1 at the mRNA level in T cells .", "annotated_text": "We previously showed that <protein>Tax</protein> induces the expression of various family members of the <protein>transcription factor AP-1</protein> such as <protein>c-Jun</protein> , <protein>JunD</protein> , <protein>c-Fos</protein> , and <protein>Fra-1</protein> at the mRNA level in <cell_type>T cells</cell_type> ."}
{"id": "3267", "text": "In this study , we have examined the ability of Tax to activate transcription through the AP-1-binding site ( AP-1 site ) .", "annotated_text": "In this study , we have examined the ability of <protein>Tax</protein> to activate transcription through the <dna>AP-1-binding site</dna> ( <dna>AP-1 site</dna> ) ."}
{"id": "3268", "text": "A transient transfection study showed that Tax can activate transcription through the AP-1-binding site in a human T cell line , whereas any combination of AP-1 proteins did so much less than Tax , indicating that the activation of the AP-1 site by Tax may require a mechanism other than the induction of AP-1 mRNA .", "annotated_text": "A transient transfection study showed that <protein>Tax</protein> can activate transcription through the <dna>AP-1-binding site</dna> in a <cell_line>human T cell line</cell_line> , whereas any combination of <protein>AP-1 proteins</protein> did so much less than <protein>Tax</protein> , indicating that the activation of the <dna>AP-1 site</dna> by <protein>Tax</protein> may require a mechanism other than the induction of <rna>AP-1 mRNA</rna> ."}
{"id": "3269", "text": "Fresh peripheral blood leukemia cells of all surveyed ATL patients displayed constitutive AP-1 DNA-binding activity , whereas no normal individuals did .", "annotated_text": "<cell_type>Fresh peripheral blood leukemia cells</cell_type> of all surveyed ATL patients displayed constitutive AP-1 DNA-binding activity , whereas no normal individuals did ."}
{"id": "3270", "text": "However , the HTLV-1 genes , including tax , are not significantly expressed in fresh leukemia cells from ATL patients .", "annotated_text": "However , the <dna>HTLV-1 genes</dna> , including <dna>tax</dna> , are not significantly expressed in fresh <cell_type>leukemia cells</cell_type> from ATL patients ."}
{"id": "3271", "text": "Our present results suggest that activation of AP-1 occurs through Tax-dependent and -independent mechanisms in HTLV-1-infected T cells , which may play some roles in dysregulated phenotypes of HTLV-1-infected cells .", "annotated_text": "Our present results suggest that activation of <protein>AP-1</protein> occurs through Tax-dependent and -independent mechanisms in HTLV-1-infected <cell_type>T cells</cell_type> , which may play some roles in dysregulated phenotypes of <cell_type>HTLV-1-infected cells</cell_type> ."}
{"id": "3272", "text": "2 , 2 ' , 4 , 6 , 6'-pentachlorobiphenyl induces apoptosis in human monocytic cells .", "annotated_text": "2 , 2 ' , 4 , 6 , 6'-pentachlorobiphenyl induces apoptosis in <cell_type>human monocytic cells</cell_type> ."}
{"id": "3273", "text": "Polychlorinatedbiphenyls ( PCBs ) are a group of persistent and widely dispersed environmental pollutants , some of which may be immunotoxic .", "annotated_text": "Polychlorinatedbiphenyls ( PCBs ) are a group of persistent and widely dispersed environmental pollutants , some of which may be immunotoxic ."}
{"id": "3274", "text": "In the present study , we investigated the effect of PCBs on immune system by assessing apoptotic cell death in human monocytic U937 cells .", "annotated_text": "In the present study , we investigated the effect of PCBs on immune system by assessing apoptotic cell death in <cell_line>human monocytic U937 cells</cell_line> ."}
{"id": "3275", "text": "Among the various congeners tested , 2 , 2 ' , 4 , 6 , 6'-pentachlorobiphenyl ( PeCB ) , a highly ortho-substituted congener , specifically induced DNA fragmentation , a hallmark of apoptosis , while the other examined di- , tri- , tetra- , and pentachlorobiphenyls did not .", "annotated_text": "Among the various congeners tested , 2 , 2 ' , 4 , 6 , 6'-pentachlorobiphenyl ( PeCB ) , a highly ortho-substituted congener , specifically induced DNA fragmentation , a hallmark of apoptosis , while the other examined di- , tri- , tetra- , and pentachlorobiphenyls did not ."}
{"id": "3276", "text": "To further study the 2 , 2 ' , 4 , 6 , 6'-PeCB-induced cell death , various features of apoptosis were examined .", "annotated_text": "To further study the 2 , 2 ' , 4 , 6 , 6'-PeCB-induced cell death , various features of apoptosis were examined ."}
{"id": "3277", "text": "2 , 2 ' , 4 , 6 , 6'-PeCB caused a decrease in cell viability and induced cellular morphologic features characteristic of apoptosis such as chromatin aggregation and apoptotic bodies .", "annotated_text": "2 , 2 ' , 4 , 6 , 6'-PeCB caused a decrease in cell viability and induced cellular morphologic features characteristic of apoptosis such as chromatin aggregation and apoptotic bodies ."}
{"id": "3278", "text": "In addition , caspase-3 , an executioner of apoptosis , was activated and its substrate , poly ( ADP-ribose ) polymerase ( PARP ) , was cleaved during 2 , 2 ' , 4 , 6 , 6'-PeCB-induced apoptosis .", "annotated_text": "In addition , <protein>caspase-3</protein> , an executioner of apoptosis , was activated and its substrate , <protein>poly ( ADP-ribose ) polymerase</protein> ( <protein>PARP</protein> ) , was cleaved during 2 , 2 ' , 4 , 6 , 6'-PeCB-induced apoptosis ."}
{"id": "3279", "text": "In contrast , 3 , 3 ' , 4 , 4 ' , 5-PeCB , a congener of coplanar structure , as well as 2 , 3 , 7 , 8-TCDD did not induce apoptosis in these human monocytic cells , although they potently induced CYP 1A1 in human hepatoma Hep G2 cells .", "annotated_text": "In contrast , 3 , 3 ' , 4 , 4 ' , 5-PeCB , a congener of coplanar structure , as well as 2 , 3 , 7 , 8-TCDD did not induce apoptosis in these <cell_type>human monocytic cells</cell_type> , although they potently induced <protein>CYP 1A1</protein> in <cell_line>human hepatoma Hep G2 cells</cell_line> ."}
{"id": "3280", "text": "Taken together , the data indicate that 2 , 2 ' , 4 , 6 , 6'-PeCB induces apoptosis in human monocytic cells through a mechanism that is independent of the arylhydrocarbon receptor .", "annotated_text": "Taken together , the data indicate that 2 , 2 ' , 4 , 6 , 6'-PeCB induces apoptosis in <cell_type>human monocytic cells</cell_type> through a mechanism that is independent of the <protein>arylhydrocarbon receptor</protein> ."}
{"id": "3281", "text": "This suggests a possibly separate mechanism by which PCBs cause immunosuppression .", "annotated_text": "This suggests a possibly separate mechanism by which PCBs cause immunosuppression ."}
{"id": "3282", "text": "Effects of deregulated Raf activation on integrin , cytokine-receptor expression and the induction of apoptosis in hematopoietic cells .", "annotated_text": "Effects of deregulated Raf activation on <protein>integrin</protein> , cytokine-receptor expression and the induction of apoptosis in <cell_type>hematopoietic cells</cell_type> ."}
{"id": "3283", "text": "The effects of deregulated Raf activation on the growth and differentiation of hematopoietic cells were investigated .", "annotated_text": "The effects of deregulated Raf activation on the growth and differentiation of <cell_type>hematopoietic cells</cell_type> were investigated ."}
{"id": "3284", "text": "The cytokine-dependent murine myeloid FDC-P1 and human erythroleukemic TF-1 cell lines were transformed to grow in response to deregulated Raf expression in the absence of exogenous cytokines .", "annotated_text": "The <cell_line>cytokine-dependent murine myeloid FDC-P1</cell_line> and <cell_line>human erythroleukemic TF-1 cell lines</cell_line> were transformed to grow in response to deregulated Raf expression in the absence of <protein>exogenous cytokines</protein> ."}
{"id": "3285", "text": "The conditionally active Raf proteins were regulated by beta-estradiol as cDNAs containing the Raf catalytic , but lacking negative-regulatory domains , were ligated to the hormone binding domain of the estrogen receptor ( deltaRaf : ER ) .", "annotated_text": "The conditionally active <protein>Raf proteins</protein> were regulated by beta-estradiol as <dna>cDNAs</dna> containing the <protein>Raf catalytic</protein> , but lacking <protein>negative-regulatory domains</protein> , were ligated to the <protein>hormone binding domain</protein> of the <protein>estrogen receptor</protein> ( <protein>deltaRaf : ER</protein> ) ."}
{"id": "3286", "text": "Continuous deltaRaf expression prevented apoptosis in the absence of exogenous cytokines and altered the morphology of the FD/deltaRaf : ER cells as they grew in large aggregated masses ( > 100 cells ) whereas the parental cytokine-dependent FDC-P1 cells grew in smaller grape-like clusters ( < 10 cells ) .", "annotated_text": "Continuous <protein>deltaRaf</protein> expression prevented apoptosis in the absence of <protein>exogenous cytokines</protein> and altered the morphology of the <cell_type>FD/deltaRaf : ER cells</cell_type> as they grew in large aggregated masses ( > 100 cells ) whereas the <cell_line>parental cytokine-dependent FDC-P1 cells</cell_line> grew in smaller grape-like clusters ( < 10 cells ) ."}
{"id": "3287", "text": "FD/deltaRaf-1 : ER cells growing in response to Raf activation displayed decreased levels of the Mac-2 and Mac-3 molecules on their cell surface .", "annotated_text": "<cell_line>FD/deltaRaf-1 : ER cells</cell_line> growing in response to Raf activation displayed decreased levels of the <protein>Mac-2 and Mac-3 molecules</protein> on their <cell_type>cell surface</cell_type> ."}
{"id": "3288", "text": "In contrast , when these cells were cultured in IL-3 , higher levels of these adhesion molecules were detected .", "annotated_text": "In contrast , when these cells were cultured in <protein>IL-3</protein> , higher levels of these <protein>adhesion molecules</protein> were detected ."}
{"id": "3289", "text": "Expression of activated Raf oncoproteins also abrogated cytokine dependency and prevented apoptosis of TF-1 cells .", "annotated_text": "Expression of activated <protein>Raf oncoproteins</protein> also abrogated cytokine dependency and prevented apoptosis of <cell_line>TF-1 cells</cell_line> ."}
{"id": "3290", "text": "Moreover , the differentiation status of these Raf-responsive cells was more immature upon Raf activation as culture with the differentiation-inducing agent phorbol 12 myristate 13-acetate ( PMA ) and beta-estradiol resulted in decreased levels of the CD11b and CD18 integrin molecules on the cell surface .", "annotated_text": "Moreover , the differentiation status of these <cell_type>Raf-responsive cells</cell_type> was more immature upon Raf activation as culture with the differentiation-inducing agent phorbol 12 myristate 13-acetate ( PMA ) and beta-estradiol resulted in decreased levels of the <protein>CD11b and CD18 integrin molecules</protein> on the <cell_type>cell surface</cell_type> ."}
{"id": "3291", "text": "In contrast when the Raf-responsive cells were induced to differentiate with PMA and GM-CSF , in the absence of deltaRaf : ER activation , increased levels of the CD11b and CD18 molecules were detected .", "annotated_text": "In contrast when the <cell_type>Raf-responsive cells</cell_type> were induced to differentiate with PMA and <protein>GM-CSF</protein> , in the absence of <protein>deltaRaf : ER</protein> activation , increased levels of the <protein>CD11b and CD18 molecules</protein> were detected ."}
{"id": "3292", "text": "Retinoic acid ( RA ) inhibited 3H-thymidine incorporation in response to GM-CSF .", "annotated_text": "Retinoic acid ( RA ) inhibited 3H-thymidine incorporation in response to <protein>GM-CSF</protein> ."}
{"id": "3293", "text": "Interestingly , Raf activation counterbalanced the inhibition of DNA synthesis caused by RA but not PMA .", "annotated_text": "Interestingly , Raf activation counterbalanced the inhibition of DNA synthesis caused by RA but not PMA ."}
{"id": "3294", "text": "Thus deregulated Raf expression can alter cytokine dependency , integrin expression and the stage of differentiation .", "annotated_text": "Thus deregulated Raf expression can alter cytokine dependency , integrin expression and the stage of differentiation ."}
{"id": "3295", "text": "These Raf-responsive cell lines will be useful in elucidating the roles of the MAP kinase cascade on hematopoietic cell differentiation and malignant transformation", "annotated_text": "These <cell_line>Raf-responsive cell lines</cell_line> will be useful in elucidating the roles of the MAP kinase cascade on <cell_type>hematopoietic cell</cell_type> differentiation and malignant transformation"}
{"id": "3296", "text": "Cyclic AMP activates p38 mitogen-activated protein kinase in Th2 cells : phosphorylation of GATA-3 and stimulation of Th2 cytokine gene expression .", "annotated_text": "Cyclic AMP activates <protein>p38 mitogen-activated protein kinase</protein> in <cell_type>Th2 cells</cell_type> : phosphorylation of <protein>GATA-3</protein> and stimulation of <cell_type>Th2</cell_type> cytokine gene expression ."}
{"id": "3297", "text": "cAMP is an important second messenger with immunomodulatory properties .", "annotated_text": "cAMP is an important second messenger with immunomodulatory properties ."}
{"id": "3298", "text": "Elevation of intracellular cAMP in T cells , induced by agents such as IL-1alpha or PGs , inhibits T cell activation .", "annotated_text": "Elevation of intracellular cAMP in <cell_type>T cells</cell_type> , induced by agents such as <protein>IL-1alpha</protein> or <protein>PGs</protein> , inhibits T cell activation ."}
{"id": "3299", "text": "In effector T cells , an increase in the level of intracellular cAMP inhibits cytokine production in Th1 cells but stimulates cytokine production in Th2 cells .", "annotated_text": "In effector <cell_type>T cells</cell_type> , an increase in the level of intracellular cAMP inhibits <protein>cytokine</protein> production in <cell_type>Th1 cells</cell_type> but stimulates <protein>cytokine</protein> production in <cell_type>Th2 cells</cell_type> ."}
{"id": "3300", "text": "Here we report that cAMP-induced effects in Th2 cells occur independently of the protein kinase A pathway , which is the major mediator of cAMP-induced signaling events in most cell types .", "annotated_text": "Here we report that cAMP-induced effects in <cell_type>Th2 cells</cell_type> occur independently of the <protein>protein kinase A</protein> pathway , which is the major mediator of cAMP-induced signaling events in most cell types ."}
{"id": "3301", "text": "Instead , cAMP stimulates activation of p38 mitogen-activated protein kinase in Th2 cells .", "annotated_text": "Instead , cAMP stimulates activation of <protein>p38 mitogen-activated protein kinase</protein> in <cell_type>Th2 cells</cell_type> ."}
{"id": "3302", "text": "This appears to be a Th2 -selective event because cAMP barely increased p38 phosphorylation in Th1 cells .", "annotated_text": "This appears to be a <cell_type>Th2</cell_type> -selective event because cAMP barely increased <protein>p38</protein> phosphorylation in <cell_type>Th1 cells</cell_type> ."}
{"id": "3303", "text": "We show that in Th2 cells , cAMP promotes the production of both IL-5 and IL-13 , which play distinct but critical roles in asthma pathogenesis .", "annotated_text": "We show that in <cell_type>Th2 cells</cell_type> , cAMP promotes the production of both <protein>IL-5</protein> and <protein>IL-13</protein> , which play distinct but critical roles in asthma pathogenesis ."}
{"id": "3304", "text": "Our data also show that cAMP causes increased phosphorylation of the transcription factor GATA-3 , which we have shown is a critical regulator of Th2 cytokine gene expression and , in turn , of airway inflammation in mice .", "annotated_text": "Our data also show that cAMP causes increased phosphorylation of the <protein>transcription factor GATA-3</protein> , which we have shown is a critical regulator of <cell_type>Th2</cell_type> cytokine gene expression and , in turn , of airway inflammation in mice ."}
{"id": "3305", "text": "Thus , Th2 -specific GATA-3 expression and p38 mitogen-activated protein kinase activation together provide a molecular basis for the differential effects of cAMP in the two T helper cell subsets .", "annotated_text": "Thus , <cell_type>Th2</cell_type> -specific <protein>GATA-3</protein> expression and <protein>p38 mitogen-activated protein kinase</protein> activation together provide a molecular basis for the differential effects of cAMP in the two <cell_type>T helper cell subsets</cell_type> ."}
{"id": "3306", "text": "Characterization of IL-4 and IL-13 signals dependent on the human IL-13 receptor alpha chain 1 : redundancy of requirement of tyrosine residue for STAT3 activation .", "annotated_text": "Characterization of <protein>IL-4</protein> and <protein>IL-13</protein> signals dependent on the <protein>human IL-13 receptor alpha chain 1</protein> : redundancy of requirement of tyrosine residue for STAT3 activation ."}
{"id": "3307", "text": "IL-4 and IL-13 are pleiotropic cytokines whose biological activities overlap with each other .", "annotated_text": "<protein>IL-4</protein> and <protein>IL-13</protein> are <protein>pleiotropic cytokines</protein> whose biological activities overlap with each other ."}
{"id": "3308", "text": "IL-13 receptor alpha chain 1 ( IL-13R alpha 1 ) is necessary for binding to IL-13 , and the heterodimer composed of IL-13R alpha 1 and IL-4R alpha chain transduces IL-13 and IL-4 signals ; however , the functional mapping of the intracellular domain of IL-13R alpha 1 is not fully understood .", "annotated_text": "<protein>IL-13 receptor alpha chain 1</protein> ( <protein>IL-13R alpha 1</protein> ) is necessary for binding to <protein>IL-13</protein> , and the heterodimer composed of <protein>IL-13R alpha 1</protein> and <protein>IL-4R alpha chain</protein> transduces <protein>IL-13</protein> and <protein>IL-4</protein> signals ; however , the functional mapping of the <protein>intracellular domain</protein> of <protein>IL-13R alpha 1</protein> is not fully understood ."}
{"id": "3309", "text": "In this study , we constructed wild and mutated types of human IL-13R alpha 1 , and analyzed IL-4 and IL-13 signals using an IL-13R alpha 1 -transfected human B cell line .", "annotated_text": "In this study , we constructed wild and mutated types of <protein>human IL-13R alpha 1</protein> , and analyzed <protein>IL-4</protein> and <protein>IL-13</protein> signals using an <protein>IL-13R alpha 1</protein> -transfected <cell_line>human B cell line</cell_line> ."}
{"id": "3310", "text": "Expression of IL-13R alpha 1 evoked STAT3 activation by IL-4 and IL-13 , and in stimulated human B cells , on which IL-13R alpha 1 was highly expressed , IL-4 and IL-13 induced STAT3 activation .", "annotated_text": "Expression of <protein>IL-13R alpha 1</protein> evoked <protein>STAT3</protein> activation by <protein>IL-4</protein> and <protein>IL-13</protein> , and in stimulated <cell_type>human B cells</cell_type> , on which <protein>IL-13R alpha 1</protein> was highly expressed , <protein>IL-4</protein> and <protein>IL-13</protein> induced <protein>STAT3</protein> activation ."}
{"id": "3311", "text": "Replacement of the two tyrosine residues completely abolished STAT3 activation , although replacing either tyrosine residue alone retained it .", "annotated_text": "Replacement of the two tyrosine residues completely abolished <protein>STAT3</protein> activation , although replacing either tyrosine residue alone retained it ."}
{"id": "3312", "text": "Furthermore , we found that the Box1 region and the C-terminal tail of IL-13R alpha 1 were critical for binding to Tyk2 , and activation of Jak1 , Tyk2 , the insulin receptor substrate-1 and STAT6 respectively .", "annotated_text": "Furthermore , we found that the <protein>Box1 region</protein> and the <protein>C-terminal tail</protein> of <protein>IL-13R alpha 1</protein> were critical for binding to <protein>Tyk2</protein> , and activation of <protein>Jak1</protein> , <protein>Tyk2</protein> , the <protein>insulin receptor substrate-1</protein> and <protein>STAT6</protein> respectively ."}
{"id": "3313", "text": "These results suggest that STAT3 activation is involved with IL-4 and IL-13 signals in human B cells along with the activation of STAT6 , and that there is a unique sequence in IL-13R alpha 1 to activate STAT3 .", "annotated_text": "These results suggest that <protein>STAT3</protein> activation is involved with <protein>IL-4</protein> and <protein>IL-13</protein> signals in <cell_type>human B cells</cell_type> along with the activation of <protein>STAT6</protein> , and that there is a unique sequence in <protein>IL-13R alpha 1</protein> to activate <protein>STAT3</protein> ."}
{"id": "3314", "text": "Functional uncoupling of the Janus kinase 3-Stat5 pathway in malignant growth of human T cell leukemia virus type 1-transformed human T cells .", "annotated_text": "Functional uncoupling of the Janus kinase 3-Stat5 pathway in malignant growth of human T cell leukemia virus type 1-transformed <cell_type>human T cells</cell_type> ."}
{"id": "3315", "text": "Human T cell leukemia virus type 1 ( HTLV-1 ) transforms cytokine -dependent T lymphocytes and causes adult T cell leukemia .", "annotated_text": "Human T cell leukemia virus type 1 ( HTLV-1 ) transforms <protein>cytokine</protein> -dependent <cell_type>T lymphocytes</cell_type> and causes adult T cell leukemia ."}
{"id": "3316", "text": "Janus tyrosine kinase ( Jak ) 3 and transcription factors Stat5a and Stat5b are essential for the proliferation of normal T cells and are constitutively hyperactivated in both HTLV-1-transformed human T cell lines and lymphocytes isolated from HTLV-1-infected patients ; therefore , a critical role for the Jak3-Stat5 pathway in the progression of this disease has been postulated .", "annotated_text": "<protein>Janus tyrosine kinase ( Jak ) 3</protein> and <protein>transcription factors</protein> <protein>Stat5a</protein> and <protein>Stat5b</protein> are essential for the proliferation of <cell_type>normal T cells</cell_type> and are constitutively hyperactivated in both <cell_line>HTLV-1-transformed human T cell lines</cell_line> and <cell_type>lymphocytes</cell_type> isolated from HTLV-1-infected patients ; therefore , a critical role for the Jak3-Stat5 pathway in the progression of this disease has been postulated ."}
{"id": "3317", "text": "We recently reported that tyrphostin AG-490 selectively blocked IL-2 activation of Jak3/Stat5 and growth of murine T cell lines .", "annotated_text": "We recently reported that tyrphostin AG-490 selectively blocked IL-2 activation of <protein>Jak3/Stat5</protein> and growth of <cell_line>murine T cell lines</cell_line> ."}
{"id": "3318", "text": "Here we demonstrate that disruption of Jak3/Stat5a/b signaling with AG-490 ( 50 & mgr ; M ) blocked the proliferation of primary human T lymphocytes , but paradoxically failed to inhibit the proliferation of HTLV-1-transformed human T cell lines , HuT-102 and MT-2 .", "annotated_text": "Here we demonstrate that disruption of Jak3/Stat5a/b signaling with AG-490 ( 50 & mgr ; M ) blocked the proliferation of <cell_type>primary human T lymphocytes</cell_type> , but paradoxically failed to inhibit the proliferation of <cell_line>HTLV-1-transformed human T cell lines</cell_line> , <cell_line>HuT-102</cell_line> and <cell_line>MT-2</cell_line> ."}
{"id": "3319", "text": "Structural homologues of AG-490 also inhibited the proliferation of primary human T cells , but not HTLV-1-infected cells .", "annotated_text": "Structural homologues of AG-490 also inhibited the proliferation of <cell_type>primary human T cells</cell_type> , but not <cell_type>HTLV-1-infected cells</cell_type> ."}
{"id": "3320", "text": "Disruption of constitutive Jak3/Stat5 activation by AG-490 was demonstrated by inhibition of 1 ) tyrosine phosphorylation of Jak3 , Stat5a ( Tyr ( 694 ) ) , and Stat5b ( Tyr ( 699 ) ) ; 2 ) serine phosphorylation of Stat5a ( Ser ( 726 ) ) as determined by a novel phosphospecific Ab ; and 3 ) Stat5a/b DNA binding to the Stat5-responsive beta-casein promoter .", "annotated_text": "Disruption of constitutive Jak3/Stat5 activation by AG-490 was demonstrated by inhibition of 1 ) tyrosine phosphorylation of <protein>Jak3</protein> , <protein>Stat5a</protein> ( Tyr ( 694 ) ) , and <protein>Stat5b</protein> ( Tyr ( 699 ) ) ; 2 ) serine phosphorylation of <protein>Stat5a</protein> ( Ser ( 726 ) ) as determined by a novel <protein>phosphospecific Ab</protein> ; and 3 ) Stat5a/b DNA binding to the <dna>Stat5-responsive beta-casein promoter</dna> ."}
{"id": "3321", "text": "In contrast , AG-490 had no effect on DNA binding by p50/p65 components of NF-kappaB , a transcription factor activated by the HTLV-1-encoded phosphoprotein , Tax .", "annotated_text": "In contrast , AG-490 had no effect on DNA binding by <protein>p50/p65 components</protein> of <protein>NF-kappaB</protein> , a <protein>transcription factor</protein> activated by the <protein>HTLV-1-encoded phosphoprotein , Tax</protein> ."}
{"id": "3322", "text": "Collectively , these data suggest that the Jak3-Stat5 pathway in HTLV-1-transformed T cells has become functionally redundant for proliferation .", "annotated_text": "Collectively , these data suggest that the Jak3-Stat5 pathway in <cell_type>HTLV-1-transformed T cells</cell_type> has become functionally redundant for proliferation ."}
{"id": "3323", "text": "Reversal of this functional uncoupling may be required before Jak3/Stat5 inhibitors will be useful in the treatment of this malignancy .", "annotated_text": "Reversal of this functional uncoupling may be required before Jak3/Stat5 inhibitors will be useful in the treatment of this malignancy ."}
{"id": "3324", "text": "The Epstein-Barr virus promoter initiating B-cell transformation is activated by RFX proteins and the B-cell-specific activator protein BSAP/Pax5 .", "annotated_text": "The <dna>Epstein-Barr virus promoter</dna> initiating B-cell transformation is activated by <protein>RFX proteins</protein> and the <protein>B-cell-specific activator protein BSAP/Pax5</protein> ."}
{"id": "3325", "text": "Epstein-Barr virus ( EBV ) -induced B-cell growth transformation , a central feature of the virus ' strategy for colonizing the human B-cell system , requires full virus latent gene expression and is initiated by transcription from the viral promoter Wp .", "annotated_text": "Epstein-Barr virus ( EBV ) -induced <cell_type>B-cell</cell_type> growth transformation , a central feature of the virus ' strategy for colonizing the human B-cell system , requires full virus latent gene expression and is initiated by transcription from the <dna>viral promoter Wp</dna> ."}
{"id": "3326", "text": "Interestingly , when EBV accesses other cell types , this growth-transforming program is not activated .", "annotated_text": "Interestingly , when EBV accesses other cell types , this growth-transforming program is not activated ."}
{"id": "3327", "text": "The present work focuses on a region of Wp which in reporter assays confers B-cell -specific activity .", "annotated_text": "The present work focuses on a region of <dna>Wp</dna> which in reporter assays confers <cell_type>B-cell</cell_type> -specific activity ."}
{"id": "3328", "text": "Bandshift studies indicate that this region contains three factor binding sites , termed sites B , C , and D , in addition to a previously characterized CREB site .", "annotated_text": "Bandshift studies indicate that this region contains three factor binding sites , termed <dna>sites B , C , and D</dna> , in addition to a previously characterized <dna>CREB site</dna> ."}
{"id": "3329", "text": "Here we show that site C binds members of the ubiquitously expressed RFX family of proteins , notably RFX1 , RFX3 , and the associated factor MIBP1 , whereas sites B and D both bind the B-cell-specific activator protein BSAP/Pax5 .", "annotated_text": "Here we show that <dna>site C</dna> binds members of the ubiquitously expressed <protein>RFX family of proteins</protein> , notably <protein>RFX1</protein> , <protein>RFX3</protein> , and the associated factor <protein>MIBP1</protein> , whereas <dna>sites B and D</dna> both bind the <protein>B-cell-specific activator protein BSAP/Pax5</protein> ."}
{"id": "3330", "text": "In reporter assays with mutant Wp constructs , the loss of factor binding to any one of these sites severely impaired promoter activity in B cells , while the wild-type promoter could be activated in non-B cells by ectopic BSAP expression .", "annotated_text": "In reporter assays with <dna>mutant Wp constructs</dna> , the loss of factor binding to any one of these sites severely impaired promoter activity in <cell_type>B cells</cell_type> , while the <dna>wild-type promoter</dna> could be activated in <cell_type>non-B cells</cell_type> by ectopic BSAP expression ."}
{"id": "3331", "text": "We suggest that Wp regulation by BSAP helps to ensure the B-cell specificity of EBV 's growth-transforming function .", "annotated_text": "We suggest that <dna>Wp</dna> regulation by <protein>BSAP</protein> helps to ensure the <cell_type>B-cell</cell_type> specificity of EBV 's growth-transforming function ."}
{"id": "3332", "text": "Activation of the Lck tyrosine protein kinase by the Herpesvirus saimiri tip protein involves two binding interactions .", "annotated_text": "Activation of the <protein>Lck tyrosine protein kinase</protein> by the Herpesvirus saimiri <protein>tip protein</protein> involves two binding interactions ."}
{"id": "3333", "text": "The Tip protein of Herpesvirus saimiri strain 484C binds to and activates the Lck tyrosine protein kinase .", "annotated_text": "The <protein>Tip protein</protein> of Herpesvirus saimiri strain 484C binds to and activates the <protein>Lck tyrosine protein kinase</protein> ."}
{"id": "3334", "text": "Two sequences in the Tip protein were previously shown to be involved in binding to Lck .", "annotated_text": "Two sequences in the <protein>Tip protein</protein> were previously shown to be involved in binding to <protein>Lck</protein> ."}
{"id": "3335", "text": "A proline-rich region , residues 132-141 , binds to the SH3 domain of the Lck protein .", "annotated_text": "A <protein>proline-rich region</protein> , residues 132-141 , binds to the <protein>SH3 domain</protein> of the <protein>Lck protein</protein> ."}
{"id": "3336", "text": "We show here that the other Lck-binding domain , residues 104-113 , binds to the carboxyl-terminal half of Lck and that this binding does not require the Lck SH3 domain .", "annotated_text": "We show here that the other <protein>Lck-binding domain</protein> , residues 104-113 , binds to the <protein>carboxyl-terminal half</protein> of <protein>Lck</protein> and that this binding does not require the <protein>Lck SH3 domain</protein> ."}
{"id": "3337", "text": "Mutated Tip containing only one functional Lck-binding domain can bind stably to Lck , although not as strongly as wild-type Tip .", "annotated_text": "Mutated <protein>Tip</protein> containing only one functional <protein>Lck-binding domain</protein> can bind stably to <protein>Lck</protein> , although not as strongly as <protein>wild-type Tip</protein> ."}
{"id": "3338", "text": "Interaction of Tip with Lck through either Lck-binding domain increases the activity of Lck in vivo .", "annotated_text": "Interaction of <protein>Tip</protein> with <protein>Lck</protein> through either <protein>Lck-binding domain</protein> increases the activity of <protein>Lck</protein> in vivo ."}
{"id": "3339", "text": "Simultaneous binding of both domains is required for maximal activation of Lck .", "annotated_text": "Simultaneous binding of both domains is required for maximal activation of <protein>Lck</protein> ."}
{"id": "3340", "text": "The transient expression of Tip in T cells was found to stimulate both Stat3 -dependent and NF-AT -dependent transcription .", "annotated_text": "The transient expression of <protein>Tip</protein> in <cell_type>T cells</cell_type> was found to stimulate both <protein>Stat3</protein> -dependent and <protein>NF-AT</protein> -dependent transcription ."}
{"id": "3341", "text": "Mutant forms of Tip lacking one or the other of the two Lck-binding domains retained the ability to stimulate Stat3 -dependent transcription .", "annotated_text": "Mutant forms of <protein>Tip</protein> lacking one or the other of the two <protein>Lck-binding domains</protein> retained the ability to stimulate <protein>Stat3</protein> -dependent transcription ."}
{"id": "3342", "text": "Tip lacking the proline-rich Lck-binding domain exhibited almost wild-type activity in this assay .", "annotated_text": "<protein>Tip</protein> lacking the proline-rich <protein>Lck-binding domain</protein> exhibited almost wild-type activity in this assay ."}
{"id": "3343", "text": "In contrast , ablation of either Lck-binding domain abolished the ability of Tip to stimulate NF-AT -dependent transcription .", "annotated_text": "In contrast , ablation of either <protein>Lck-binding domain</protein> abolished the ability of <protein>Tip</protein> to stimulate <protein>NF-AT</protein> -dependent transcription ."}
{"id": "3344", "text": "Full biological activity of Tip , therefore , appears to require both Lck-binding domains .", "annotated_text": "Full biological activity of <protein>Tip</protein> , therefore , appears to require both <protein>Lck-binding domains</protein> ."}
{"id": "3345", "text": "Accumulation of RXR alpha during activation of cycling human T lymphocytes : modulation of RXRE transactivation function by mitogen-activated protein kinase pathways .", "annotated_text": "Accumulation of <protein>RXR alpha</protein> during activation of cycling <cell_type>human T lymphocytes</cell_type> : modulation of RXRE transactivation function by mitogen-activated protein kinase pathways ."}
{"id": "3346", "text": "We have previously reported that the activation of resting human immature peripheral blood T ( PBT ) lymphocytes is associated with the loss of retinoid X receptor alpha ( RXRalpha ) expression .", "annotated_text": "We have previously reported that the activation of resting <cell_type>human immature peripheral blood T ( PBT ) lymphocytes</cell_type> is associated with the loss of <protein>retinoid X receptor alpha</protein> ( <protein>RXRalpha</protein> ) expression ."}
{"id": "3347", "text": "In the present study , we have demonstrated that , unlike resting cells , activation of cycling human mature PBT lymphocytes , and T lymphocyte leukemia cell lines is accompanied by the accumulation of RXRalpha mRNA and protein .", "annotated_text": "In the present study , we have demonstrated that , unlike resting cells , activation of <cell_type>cycling human mature PBT lymphocytes</cell_type> , and <cell_line>T lymphocyte leukemia cell lines</cell_line> is accompanied by the accumulation of <protein>RXRalpha</protein> mRNA and protein ."}
{"id": "3348", "text": "Interestingly , cyclosporin A further augmented RXRalpha expression , indicating the involvement of calcineurin pathways in the process .", "annotated_text": "Interestingly , cyclosporin A further augmented <protein>RXRalpha</protein> expression , indicating the involvement of calcineurin pathways in the process ."}
{"id": "3349", "text": "9-cis retinoic acid inhibited the accumulation , suggesting that retinoids can regulate the synthesis of their own receptors during T cell activation .", "annotated_text": "9-cis retinoic acid inhibited the accumulation , suggesting that retinoids can regulate the synthesis of their own receptors during T cell activation ."}
{"id": "3350", "text": "Transfection analysis in Jurkat cells , using RXRE-dependent reporter assays , showed that RXRalpha accumulated during T cell activation was transcriptionally inactive .", "annotated_text": "Transfection analysis in <cell_line>Jurkat cells</cell_line> , using RXRE-dependent reporter assays , showed that <protein>RXRalpha</protein> accumulated during T cell activation was transcriptionally inactive ."}
{"id": "3351", "text": "To investigate the mechanism of such inhibition , the role of two mitogen-activated protein kinase pathways , c-Jun N-terminal kinase ( JNK ) and extracellular signal-regulated kinase ( ERK ) , in modulating RXRE-dependent transcription , was explored .", "annotated_text": "To investigate the mechanism of such inhibition , the role of two mitogen-activated protein kinase pathways , <protein>c-Jun N-terminal kinase</protein> ( <protein>JNK</protein> ) and <protein>extracellular signal-regulated kinase</protein> ( <protein>ERK</protein> ) , in modulating RXRE-dependent transcription , was explored ."}
{"id": "3352", "text": "The expression of constitutively active MAP/ERK kinase kinase 1 ( MEKK1 ) inhibited RXRE-dependent transcription , whereas dominant negative MEKK1 increased the transcription , indicating the involvement of JNK signaling pathways in the process .", "annotated_text": "The expression of constitutively active <protein>MAP/ERK kinase kinase 1</protein> ( <protein>MEKK1</protein> ) inhibited RXRE-dependent transcription , whereas <protein>dominant negative MEKK1</protein> increased the transcription , indicating the involvement of <protein>JNK</protein> signaling pathways in the process ."}
{"id": "3353", "text": "In contrast , expression of constitutively active MEK1 , which activates ERK pathway , enhanced RXRE-dependent activation .", "annotated_text": "In contrast , expression of <protein>constitutively active MEK1</protein> , which activates <protein>ERK</protein> pathway , enhanced RXRE-dependent activation ."}
{"id": "3354", "text": "When both were activated simultaneously , JNK pathway was dominant over ERK pathway and resulted in inhibition of RXRE-mediated transcription .", "annotated_text": "When both were activated simultaneously , <protein>JNK</protein> pathway was dominant over <protein>ERK</protein> pathway and resulted in inhibition of RXRE-mediated transcription ."}
{"id": "3355", "text": "These data demonstrate a dual regulatory control of RXRalpha expression during the activation of resting and cycling T lymphocytes and indicate a dynamic balance between JNK and ERK pathways in modulating RXRE-mediated transactivation .", "annotated_text": "These data demonstrate a dual regulatory control of <protein>RXRalpha</protein> expression during the activation of <cell_type>resting and cycling T lymphocytes</cell_type> and indicate a dynamic balance between JNK and ERK pathways in modulating RXRE-mediated transactivation ."}
{"id": "3356", "text": "The proteasome regulates receptor-mediated endocytosis of interleukin-2 .", "annotated_text": "The <protein>proteasome</protein> regulates receptor-mediated endocytosis of <protein>interleukin-2</protein> ."}
{"id": "3357", "text": "Recent studies have increasingly implicated the proteasome in the regulation of cell surface receptors .", "annotated_text": "Recent studies have increasingly implicated the <protein>proteasome</protein> in the regulation of <protein>cell surface receptors</protein> ."}
{"id": "3358", "text": "In the present study , we investigated the role of the proteasome for ligand-dependent endocytosis and degradation of the interleukin-2 ( IL-2 ) -interleukin-2 receptor ( IL-2R ) complex .", "annotated_text": "In the present study , we investigated the role of the <protein>proteasome</protein> for ligand-dependent endocytosis and degradation of the <protein>interleukin-2 ( IL-2 ) -interleukin-2 receptor ( IL-2R ) complex</protein> ."}
{"id": "3359", "text": "Proteasome inhibitors impaired internalization of IL-2.IL-2R and prevented the lysosomal degradation of this cytokine .", "annotated_text": "Proteasome inhibitors impaired internalization of <protein>IL-2.IL-2R</protein> and prevented the lysosomal degradation of this <protein>cytokine</protein> ."}
{"id": "3360", "text": "Based on time-course studies , proteasome activity is primarily required after initial endocytosis of the IL-2.IL-2R .", "annotated_text": "Based on time-course studies , <protein>proteasome</protein> activity is primarily required after initial endocytosis of the <protein>IL-2.IL-2R</protein> ."}
{"id": "3361", "text": "Proteasome function was also necessary for the lysosomal degradation of IL-2 internalized by IL-2R that were comprised of cytoplasmic tailless beta- or gamma c-subunits , suggesting that the target protein for the proteasome is independent of either the cytoplasmic tail of the IL-2R beta- or gamma c-subunits and their associated signaling components .", "annotated_text": "Proteasome function was also necessary for the lysosomal degradation of <protein>IL-2</protein> internalized by <protein>IL-2R</protein> that were comprised of <protein>cytoplasmic tailless</protein> <protein>beta- or gamma c-subunits</protein> , suggesting that the target protein for the <protein>proteasome</protein> is independent of either the <protein>cytoplasmic tail</protein> of the <protein>IL-2R</protein> <protein>beta- or gamma c-subunits</protein> and their associated signaling components ."}
{"id": "3362", "text": "Therefore , a functional proteasome is required for optimal endocytosis of the IL-2R/ligand complex and is essential for the subsequent lysosomal degradation of IL-2 , possibly by regulating trafficking to the lysosome .", "annotated_text": "Therefore , a functional <protein>proteasome</protein> is required for optimal endocytosis of the <protein>IL-2R/ligand complex</protein> and is essential for the subsequent lysosomal degradation of <protein>IL-2</protein> , possibly by regulating trafficking to the lysosome ."}
{"id": "3363", "text": "Functional characterization of the two alternative promoters of human p45 NF-E2 gene .", "annotated_text": "Functional characterization of the two alternative promoters of <dna>human p45 NF-E2 gene</dna> ."}
{"id": "3364", "text": "OBJECTIVE : The transcription factor NF-E2 , a heterodimeric protein complex composed of p45 and small Maf family proteins , is considered crucial for the proper differentiation of erythrocytes and megakaryocytes in vivo .", "annotated_text": "OBJECTIVE : The <protein>transcription factor NF-E2</protein> , a <protein>heterodimeric protein complex</protein> composed of <protein>p45</protein> and small <protein>Maf family proteins</protein> , is considered crucial for the proper differentiation of <cell_type>erythrocytes</cell_type> and <cell_type>megakaryocytes</cell_type> in vivo ."}
{"id": "3365", "text": "We report the results of studies aimed at understanding the regulatory mechanisms controlling p45 gene expression in erythroid cells .", "annotated_text": "We report the results of studies aimed at understanding the regulatory mechanisms controlling <dna>p45 gene</dna> expression in <cell_type>erythroid cells</cell_type> ."}
{"id": "3366", "text": "MATERIALS AND METHODS : Human p45 mRNAs have two alternative isoforms , aNF-E2 and fNF-E2 , and these isoforms are transcribed from the alternative promoters .", "annotated_text": "MATERIALS AND METHODS : <rna>Human p45 mRNAs</rna> have two alternative isoforms , <rna>aNF-E2</rna> and <rna>fNF-E2</rna> , and these isoforms are transcribed from the <dna>alternative promoters</dna> ."}
{"id": "3367", "text": "We investigated lineage-specific expression of both isomers in human erythroid and megakaryocytic cells by reverse transcriptase polymerase chain reaction or Northern blot analysis .", "annotated_text": "We investigated lineage-specific expression of both isomers in human <cell_type>erythroid and megakaryocytic cells</cell_type> by reverse transcriptase polymerase chain reaction or Northern blot analysis ."}
{"id": "3368", "text": "For functional characterization of both promoters , plasmids in which reporter genes were placed under the control of a series of truncated or mutated promoter fragments were transfected to human hematopoietic cell lines .", "annotated_text": "For functional characterization of both promoters , plasmids in which <dna>reporter genes</dna> were placed under the control of a series of truncated or mutated <dna>promoter fragments</dna> were transfected to <cell_line>human hematopoietic cell lines</cell_line> ."}
{"id": "3369", "text": "RESULTS : When CD34 ( + ) cells isolated from human cord blood were induced to unilineage erythroid or megakaryocytic differentiation in liquid suspension culture , both transcripts , although barely detected at day 0 , were induced in both erythroid and megakaryocytic cultures .", "annotated_text": "RESULTS : When <cell_type>CD34 ( + ) cells</cell_type> isolated from human cord blood were induced to unilineage erythroid or megakaryocytic differentiation in liquid suspension culture , both transcripts , although barely detected at day 0 , were induced in both erythroid and megakaryocytic cultures ."}
{"id": "3370", "text": "fNF-E2 mRNA was found to be more abundant in erythroid cells than megakaryocytic cells at day 7 of culture .", "annotated_text": "<rna>fNF-E2 mRNA</rna> was found to be more abundant in <cell_type>erythroid cells</cell_type> than <cell_type>megakaryocytic cells</cell_type> at day 7 of culture ."}
{"id": "3371", "text": "Although both isomers were expressed in human erythroid-megakaryocytic cell lines , megakaryocytic maturation with loss of erythroid phenotype induced by phorbol 12-myristate 13-acetate ( PMA ) resulted in exclusive downregulation of fNF-E2 , suggesting that fNF-E2 promoter is more erythroid specific .", "annotated_text": "Although both isomers were expressed in <cell_line>human erythroid-megakaryocytic cell lines</cell_line> , megakaryocytic maturation with loss of erythroid phenotype induced by phorbol 12-myristate 13-acetate ( PMA ) resulted in exclusive downregulation of <rna>fNF-E2</rna> , suggesting that <dna>fNF-E2 promoter</dna> is more erythroid specific ."}
{"id": "3372", "text": "Functional analysis of fNF-E2 promoter showed that the promoter is active only in erythroid-megakaryocytic cells and that the double GATA sit e in the proximal region is necessary for its efficient activity .", "annotated_text": "Functional analysis of <dna>fNF-E2 promoter</dna> showed that the promoter is active only in <cell_type>erythroid-megakaryocytic cells</cell_type> and that the <dna>double GATA sit</dna> e in the proximal region is necessary for its efficient activity ."}
{"id": "3373", "text": "CONCLUSION : These results suggest that GATA proteins , which govern the differentiation of erythroid lineage cells , are required for full promoter activity of the p45 gene .", "annotated_text": "CONCLUSION : These results suggest that <protein>GATA proteins</protein> , which govern the differentiation of <cell_type>erythroid lineage cells</cell_type> , are required for full promoter activity of the <dna>p45 gene</dna> ."}
{"id": "3374", "text": "Transcriptional activation of heme oxygenase-1 and its functional significance in acetaminophen-induced hepatitis and hepatocellular injury in the rat .", "annotated_text": "Transcriptional activation of <dna>heme oxygenase-1</dna> and its functional significance in acetaminophen-induced hepatitis and hepatocellular injury in the rat ."}
{"id": "3375", "text": "BACKGROUND/AIM : Glutathione depletion contributes to acetaminophen hepatotoxicity and is known to induce the oxidative stress reactant heme oxygenase-1 .", "annotated_text": "BACKGROUND/AIM : Glutathione depletion contributes to acetaminophen hepatotoxicity and is known to induce the oxidative stress reactant <protein>heme oxygenase-1</protein> ."}
{"id": "3376", "text": "The metabolites of the heme oxygenase pathway , biliverdin , carbon monoxide , and iron may modulate acetaminophen toxicity .", "annotated_text": "The metabolites of the heme oxygenase pathway , biliverdin , carbon monoxide , and iron may modulate acetaminophen toxicity ."}
{"id": "3377", "text": "The aim of this study was to assess cell-type specific expression of heme oxygenase-1 and its impact on liver injury and microcirculatory disturbances in a model of acetaminophen-induced hepatitis .", "annotated_text": "The aim of this study was to assess cell-type specific expression of <dna>heme oxygenase-1</dna> and its impact on liver injury and microcirculatory disturbances in a model of acetaminophen-induced hepatitis ."}
{"id": "3378", "text": "METHODS : Gene expression of heme oxygenase-1 was studied by Northern- and Western analysis as well as immunohistochemistry .", "annotated_text": "METHODS : Gene expression of <dna>heme oxygenase-1</dna> was studied by Northern- and Western analysis as well as immunohistochemistry ."}
{"id": "3379", "text": "The time course of heme oxygenase-1 and -2 , cytokine-induced neutrophil chemoattractant-1 , and intercellular adhesion molecule-1 was studied by Northern analysis .", "annotated_text": "The time course of <protein>heme oxygenase-1 and -2</protein> , <protein>cytokine-induced neutrophil chemoattractant-1</protein> , and <protein>intercellular adhesion molecule-1</protein> was studied by Northern analysis ."}
{"id": "3380", "text": "DNA-binding activity of nuclear factor-kappaB was determined by electrophoretic mobility shift assay .", "annotated_text": "DNA-binding activity of <protein>nuclear factor-kappaB</protein> was determined by electrophoretic mobility shift assay ."}
{"id": "3381", "text": "Sinusoidal perfusion and leukocyte-endothelial interactions were assessed by intravital microscopy .", "annotated_text": "Sinusoidal perfusion and leukocyte-endothelial interactions were assessed by intravital microscopy ."}
{"id": "3382", "text": "RESULTS : Acetaminophen caused a moderate sinusoidal perfusion failure ( -15 % ) and infiltration of neutrophils along with activation of nuclear factor-kappaB and intercellular adhesion molecule-1 and cytokine-induced neutrophil chemoattractant-1 mRNAs .", "annotated_text": "RESULTS : Acetaminophen caused a moderate sinusoidal perfusion failure ( -15 % ) and infiltration of <cell_type>neutrophils</cell_type> along with activation of <protein>nuclear factor-kappaB</protein> and <protein>intercellular adhesion molecule-1</protein> and <protein>cytokine-induced neutrophil chemoattractant-1</protein> mRNAs ."}
{"id": "3383", "text": "Induction of heme oxygenase-1 mRNA and protein ( approximately 30-fold ) in hepatocytes and non-parenchymal cells paralleled the inflammatory response .", "annotated_text": "Induction of <protein>heme oxygenase-1</protein> mRNA and protein ( approximately 30-fold ) in <cell_type>hepatocytes</cell_type> and <cell_type>non-parenchymal cells</cell_type> paralleled the inflammatory response ."}
{"id": "3384", "text": "Blockade of heme oxygenase activity with tin-protoporphyrin-IX abrogated acetaminophen-induced hepatic neutrophil accumulation and nuclear factor-kappaB activation , but failed to affect sinusoidal perfusion and liver injury .", "annotated_text": "Blockade of heme oxygenase activity with tin-protoporphyrin-IX abrogated acetaminophen-induced <cell_type>hepatic neutrophil</cell_type> accumulation and <protein>nuclear factor-kappaB</protein> activation , but failed to affect sinusoidal perfusion and liver injury ."}
{"id": "3385", "text": "CONCLUSIONS : The inflammatory response associated with acetaminophen hepatotoxicity is modulated by the parallel induction of the heme oxygenase-1 gene .", "annotated_text": "CONCLUSIONS : The inflammatory response associated with acetaminophen hepatotoxicity is modulated by the parallel induction of the <dna>heme oxygenase-1 gene</dna> ."}
{"id": "3386", "text": "However , heme oxygenase-1 has no permissive effect on sinusoidal perfusion and does not affect liver injury in this model .", "annotated_text": "However , <dna>heme oxygenase-1</dna> has no permissive effect on sinusoidal perfusion and does not affect liver injury in this model ."}
{"id": "3387", "text": "These data argue against a central role of nuclear factor-kappaB activation and neutrophil infiltration as perpetuating factors of liver injury in acetaminophen toxicity .", "annotated_text": "These data argue against a central role of <protein>nuclear factor-kappaB</protein> activation and neutrophil infiltration as perpetuating factors of liver injury in acetaminophen toxicity ."}
{"id": "3388", "text": "Tumor necrosis factor-alpha -induced proliferation requires synthesis of granulocyte-macrophage colony-stimulating factor .", "annotated_text": "<protein>Tumor necrosis factor-alpha</protein> -induced proliferation requires synthesis of <protein>granulocyte-macrophage colony-stimulating factor</protein> ."}
{"id": "3389", "text": "OBJECTIVE : Tumor necrosis factor- alpha ( TNF-alpha ) induces a variety of cellular responses , some of them being at least seemingly contradictory .", "annotated_text": "OBJECTIVE : <protein>Tumor necrosis factor- alpha</protein> ( <protein>TNF-alpha</protein> ) induces a variety of cellular responses , some of them being at least seemingly contradictory ."}
{"id": "3390", "text": "Thus , we set out to find differences in the modes of proliferative and apoptotic responses to TNF- alpha .", "annotated_text": "Thus , we set out to find differences in the modes of proliferative and apoptotic responses to <protein>TNF- alpha</protein> ."}
{"id": "3391", "text": "MATERIALS AND METHODS : We screened a panel of acute myeloid leukemia-derived cell lines for TNF- alpha -responsiveness .", "annotated_text": "MATERIALS AND METHODS : We screened a panel of <cell_line>acute myeloid leukemia-derived cell lines</cell_line> for <protein>TNF- alpha</protein> -responsiveness ."}
{"id": "3392", "text": "In two lines ( OCI-AML-1 , OCI-AML-11 ) , TNF- alpha acted as an apoptotic agent ; in others ( HU-3 , M-07e , TF-1 ) , it had the opposite effect , preventing apoptosis and inducing proliferation .", "annotated_text": "In two lines ( <cell_line>OCI-AML-1</cell_line> , <cell_line>OCI-AML-11</cell_line> ) , <protein>TNF- alpha</protein> acted as an apoptotic agent ; in others ( <cell_line>HU-3</cell_line> , <cell_line>M-07e</cell_line> , <cell_line>TF-1</cell_line> ) , it had the opposite effect , preventing apoptosis and inducing proliferation ."}
{"id": "3393", "text": "Direct and indirect signaling mechanisms , including NF-kappaB activation and cytokine synthesis , were analyzed .", "annotated_text": "Direct and indirect signaling mechanisms , including <protein>NF-kappaB</protein> activation and cytokine synthesis , were analyzed ."}
{"id": "3394", "text": "RESULTS : All cell lines tested expressed TNF- alpha receptors I and II and responded to TNF- alpha by upregulation of intercellular adhesion molecule-1 .", "annotated_text": "RESULTS : All cell lines tested expressed <protein>TNF- alpha receptors I and II</protein> and responded to <protein>TNF- alpha</protein> by upregulation of <protein>intercellular adhesion molecule-1</protein> ."}
{"id": "3395", "text": "In contrast to granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , TNF- alpha did not activate the MAP kinase and p70S6 kinase pathways .", "annotated_text": "In contrast to <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) , <protein>TNF- alpha</protein> did not activate the <protein>MAP kinase</protein> and p70S6 kinase pathways ."}
{"id": "3396", "text": "Nevertheless , inhibitors of these pathways clearly reduced the TNF-alpha -induced cell growth , indicating that TNF- alpha-proliferative cells produced a growth factor that induced proliferation upon stimulation of the above pathways .", "annotated_text": "Nevertheless , inhibitors of these pathways clearly reduced the <protein>TNF-alpha</protein> -induced cell growth , indicating that <cell_type>TNF- alpha-proliferative cells</cell_type> produced a growth factor that induced proliferation upon stimulation of the above pathways ."}
{"id": "3397", "text": "Anti-GM-CSF antibodies inhibited the TNF-alpha -induced growth , suggesting the presence of an autocrine loop for cell proliferation mediated by GM-CSF .", "annotated_text": "<protein>Anti-GM-CSF antibodies</protein> inhibited the <protein>TNF-alpha</protein> -induced growth , suggesting the presence of an autocrine loop for cell proliferation mediated by <protein>GM-CSF</protein> ."}
{"id": "3398", "text": "Supporting this notion , TNF-alpha -induced upregulation of GM-CSF mRNA levels and protein secretion in the TNF-alpha -proliferative , but not in the TNF-alpha-apoptotic cell lines .", "annotated_text": "Supporting this notion , <protein>TNF-alpha</protein> -induced upregulation of <rna>GM-CSF mRNA</rna> levels and protein secretion in the <protein>TNF-alpha</protein> -proliferative , but not in the <cell_line>TNF-alpha-apoptotic cell lines</cell_line> ."}
{"id": "3399", "text": "CONCLUSION : These data identify GM-CSF synthesis as an early and essential step in TNF- alpha-induced proliferation .", "annotated_text": "CONCLUSION : These data identify <protein>GM-CSF</protein> synthesis as an early and essential step in TNF- alpha-induced proliferation ."}
{"id": "3400", "text": "We show for the first time that TNF-alpha-treated cell lines producing no or only minimal amounts of GM-CSF demonstrate an apoptotic phenotype , while cell lines with high GM-CSF expression rates can escape from growth arrest or even apoptosis .", "annotated_text": "We show for the first time that <cell_line>TNF-alpha-treated cell lines</cell_line> producing no or only minimal amounts of <protein>GM-CSF</protein> demonstrate an apoptotic phenotype , while cell lines with high <protein>GM-CSF</protein> expression rates can escape from growth arrest or even apoptosis ."}
{"id": "3401", "text": "In this context , we discuss arguments pointing at NF-kappaB as regulator of GM-CSF synthesis and thus indirectly as regulator for the escape of TNF-alpha -induced apoptosis", "annotated_text": "In this context , we discuss arguments pointing at <protein>NF-kappaB</protein> as regulator of <protein>GM-CSF</protein> synthesis and thus indirectly as regulator for the escape of <protein>TNF-alpha</protein> -induced apoptosis"}
{"id": "3402", "text": "Glucocorticoid receptor content of T lymphocytes : evidence for heterogeneity .", "annotated_text": "<protein>Glucocorticoid receptor</protein> content of <cell_type>T lymphocytes</cell_type> : evidence for heterogeneity ."}
{"id": "3403", "text": "Glucocorticoid receptors were measured in T lymphocytes that were isolated from peripheral blood by either nylon wool filtration or E-rosette sedimentation .", "annotated_text": "<protein>Glucocorticoid receptors</protein> were measured in <cell_type>T lymphocytes</cell_type> that were isolated from peripheral blood by either nylon wool filtration or E-rosette sedimentation ."}
{"id": "3404", "text": "T cells isolated by nylon wool filtration specifically bind 6.7 +/- 0.2 fmol of dexamethasone per million cells ( equivalent to 4000 +/- 200 receptors per cell ) , whereas T cells isolated by E-rosette sedimentation bind 12.0 +/- 0.7 fmol of dexamethasone per million cells ( equivalent to 7200 +/- 400 receptors per cell ) .", "annotated_text": "<cell_type>T cells</cell_type> isolated by nylon wool filtration specifically bind 6.7 +/- 0.2 fmol of dexamethasone per million cells ( equivalent to 4000 +/- 200 receptors per cell ) , whereas <cell_type>T cells</cell_type> isolated by E-rosette sedimentation bind 12.0 +/- 0.7 fmol of dexamethasone per million cells ( equivalent to 7200 +/- 400 receptors per cell ) ."}
{"id": "3405", "text": "This difference in the amount of dexamethasone bound by the two T cell preparations was significant ( p less than .001 ) and was present immediately after cell isolation .", "annotated_text": "This difference in the amount of dexamethasone bound by the two T cell preparations was significant ( p less than .001 ) and was present immediately after cell isolation ."}
{"id": "3406", "text": "The binding affinities of the different T cell preparations for dexamethasone were similar .", "annotated_text": "The binding affinities of the different <cell_line>T cell preparations</cell_line> for dexamethasone were similar ."}
{"id": "3407", "text": "T cells that are isolated by a combination of nylon wool filtration followed by E-rosette sedimentation bind the same amount of dexamethasone as T cells isolated by nylon wool filtration alone .", "annotated_text": "T cells that are isolated by a combination of nylon wool filtration followed by E-rosette sedimentation bind the same amount of dexamethasone as <cell_type>T cells</cell_type> isolated by nylon wool filtration alone ."}
{"id": "3408", "text": "T cells isolated by a combination of E-rosette sedimentation following by nylon wool filtration bind less dexamethasone than do T cells isolated by E-rosette sedimentation alone .", "annotated_text": "<cell_type>T cells</cell_type> isolated by a combination of E-rosette sedimentation following by nylon wool filtration bind less dexamethasone than do <cell_type>T cells</cell_type> isolated by E-rosette sedimentation alone ."}
{"id": "3409", "text": "These findings suggest that T cells are heterogeneous with respect to their quantity of glucocorticoid receptors .", "annotated_text": "These findings suggest that <cell_type>T cells</cell_type> are heterogeneous with respect to their quantity of <protein>glucocorticoid receptors</protein> ."}
{"id": "3410", "text": "Isolation of T cells by E-rosette sedimentation enriches for T cells that have a greater number of glucocorticoid receptors , and isolation of T cells by nylon wool filtration enriches for T cells that have a lesser number of glucocorticoid receptors .", "annotated_text": "Isolation of <cell_type>T cells</cell_type> by E-rosette sedimentation enriches for <cell_type>T cells</cell_type> that have a greater number of <protein>glucocorticoid receptors</protein> , and isolation of <cell_type>T cells</cell_type> by nylon wool filtration enriches for <cell_type>T cells</cell_type> that have a lesser number of <protein>glucocorticoid receptors</protein> ."}
{"id": "3411", "text": "Glucocorticoid receptors and glucocorticoid sensitivity of human leukemic cells .", "annotated_text": "<protein>Glucocorticoid receptors</protein> and glucocorticoid sensitivity of <cell_type>human leukemic cells</cell_type> ."}
{"id": "3412", "text": "We have established optimal conditions for the measurement of glucocorticoid receptors ( GR ) in human white cells using a whole-cell binding assay with [ 3H ] dexamethasone as the ligand , and the subsequent determination of the GR content in normal human lymphocytes and in leukemic cells of patients with various forms of acute and chronic leukemia .", "annotated_text": "We have established optimal conditions for the measurement of <protein>glucocorticoid receptors</protein> ( <protein>GR</protein> ) in <cell_type>human white cells</cell_type> using a whole-cell binding assay with [ 3H ] dexamethasone as the ligand , and the subsequent determination of the <protein>GR</protein> content in <cell_type>normal human lymphocytes</cell_type> and in <cell_type>leukemic cells</cell_type> of patients with various forms of acute and chronic leukemia ."}
{"id": "3413", "text": "A number of leukemia cell lines in continuous culture were also subjected to the GR assay , and the results were correlated with the sensitivity of these cell lines to glucocorticoid steroids in vitro .", "annotated_text": "A number of <cell_line>leukemia cell lines</cell_line> in continuous culture were also subjected to the <protein>GR</protein> assay , and the results were correlated with the sensitivity of these <cell_line>cell lines</cell_line> to glucocorticoid steroids in vitro ."}
{"id": "3414", "text": "The GR content of normal human lymphocytes amounted to 4 , 850 +/- 1 , 340 ( mean +/- SD ) receptors/cell .", "annotated_text": "The <protein>GR</protein> content of <cell_type>normal human lymphocytes</cell_type> amounted to 4 , 850 +/- 1 , 340 ( mean +/- SD ) receptors/cell ."}
{"id": "3415", "text": "The mean equilibrium dissociation constant ( KD ) of the interaction of [ 3H ] dexamethasone with the GR was 1.2 x 10 ( -8 ) M .", "annotated_text": "The mean equilibrium dissociation constant ( KD ) of the interaction of [ 3H ] dexamethasone with the <protein>GR</protein> was 1.2 x 10 ( -8 ) M ."}
{"id": "3416", "text": "Steroidal compounds with a known glucocorticoid potency effectively competed for the binding , whereas steroids devoid of glucocorticoid activity ( e.g. estradiol-17 beta and testosterone ) were ineffective .", "annotated_text": "Steroidal compounds with a known glucocorticoid potency effectively competed for the binding , whereas steroids devoid of glucocorticoid activity ( e.g. estradiol-17 beta and testosterone ) were ineffective ."}
{"id": "3417", "text": "The GR content of the blast cells obtained from eight patients suffering from acute leukemia and four patients with a blast crisis of chronic myelocytic leukemia was found to be highly variable ( 3 , 230-29 , 900 receptors/cell ) , while the lymphocytes of six patients with chronic lymphatic leukemia contained a rather stable GR content ( 2 , 930-5 , 120 receptors/cell ) , which was comparable with that of normal lymphocytes .", "annotated_text": "The <protein>GR</protein> content of the <cell_type>blast cells</cell_type> obtained from eight patients suffering from acute leukemia and four patients with a blast crisis of chronic myelocytic leukemia was found to be highly variable ( 3 , 230-29 , 900 receptors/cell ) , while the <cell_type>lymphocytes</cell_type> of six patients with chronic lymphatic leukemia contained a rather stable <protein>GR</protein> content ( 2 , 930-5 , 120 receptors/cell ) , which was comparable with that of <cell_type>normal lymphocytes</cell_type> ."}
{"id": "3418", "text": "GR was identified in all the 12 malignant continuous white cell lines studied .", "annotated_text": "<protein>GR</protein> was identified in all the 12 <cell_line>malignant continuous white cell lines</cell_line> studied ."}
{"id": "3419", "text": "Large cells contained more GR than the smaller ones .", "annotated_text": "Large cells contained more <protein>GR</protein> than the smaller ones ."}
{"id": "3420", "text": "There was no apparent correlation between the GR concentration and the sensitivity of the cells in vitro to glucocorticoids as judged by [ 3H ] thymidine incorporation studies .", "annotated_text": "There was no apparent correlation between the <protein>GR</protein> concentration and the sensitivity of the cells in vitro to glucocorticoids as judged by [ 3H ] thymidine incorporation studies ."}
{"id": "3421", "text": "Distribution of the surface markers in the leukemic cell lines did not relate to the GR concentration .", "annotated_text": "Distribution of the surface markers in the <cell_line>leukemic cell lines</cell_line> did not relate to the <protein>GR</protein> concentration ."}
{"id": "3422", "text": "We conclude that the presence of GR is probably a universal feature of the leukemic cells , and , from a clinical standpoint , probably does not alone imply steroid responsiveness .", "annotated_text": "We conclude that the presence of <protein>GR</protein> is probably a universal feature of the <cell_type>leukemic cells</cell_type> , and , from a clinical standpoint , probably does not alone imply steroid responsiveness ."}
{"id": "3423", "text": "Evidence for a steroid receptor in rheumatoid synovial tissue cells .", "annotated_text": "Evidence for a <protein>steroid receptor</protein> in <cell_type>rheumatoid synovial tissue cells</cell_type> ."}
{"id": "3424", "text": "One mechanism by which glucocorticoids could exert their anti-inflammatory action is via rapidly saturable , stereo-specific cytoplasmic protein receptors .", "annotated_text": "One mechanism by which glucocorticoids could exert their anti-inflammatory action is via rapidly saturable , <protein>stereo-specific cytoplasmic protein receptors</protein> ."}
{"id": "3425", "text": "This report is of an investigation into such a possibility in synovial cells .", "annotated_text": "This report is of an investigation into such a possibility in <cell_type>synovial cells</cell_type> ."}
{"id": "3426", "text": "Synovium , obtained from knee joints of rheumatoid patients undergoing surgery , was incubated with clostridiopeptidase A and trypsin-EDTA to obtain cell suspensions .", "annotated_text": "Synovium , obtained from knee joints of rheumatoid patients undergoing surgery , was incubated with <protein>clostridiopeptidase A</protein> and <protein>trypsin-EDTA</protein> to obtain cell suspensions ."}
{"id": "3427", "text": "These , together with cells obtained from synovial fluid aspirated from patients with rheumatoid arthritis , were identified by electron microscopy .", "annotated_text": "These , together with cells obtained from synovial fluid aspirated from patients with rheumatoid arthritis , were identified by electron microscopy ."}
{"id": "3428", "text": "Duplicate samples of these cell suspensions were incubated with increasing concentrations of H3Dexamethasone ( 1 x 10 ( -10 ) M-1 x 10 ( -9 ) M ) for 30 minutes at 37 degrees C .", "annotated_text": "Duplicate samples of these cell suspensions were incubated with increasing concentrations of H3Dexamethasone ( 1 x 10 ( -10 ) M-1 x 10 ( -9 ) M ) for 30 minutes at 37 degrees C ."}
{"id": "3429", "text": "Analysis of the proportion of steroid bound to whole cells showed evidence for specific , rapidly saturable , receptors in the cells obtained from synovial tissue , but this was not found in synovial fluid cells .", "annotated_text": "Analysis of the proportion of steroid bound to <cell_type>whole cells</cell_type> showed evidence for specific , rapidly saturable , receptors in the cells obtained from synovial tissue , but this was not found in <cell_type>synovial fluid cells</cell_type> ."}
{"id": "3430", "text": "Electron micrographs showed that cells obtained from synovial tissue consisted of synovial fibroblast - and macrophage-types , lymphocytes , monocytes and macrophages .", "annotated_text": "Electron micrographs showed that cells obtained from synovial tissue consisted of <cell_type>synovial fibroblast</cell_type> - and <cell_type>macrophage-types</cell_type> , <cell_type>lymphocytes</cell_type> , <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> ."}
{"id": "3431", "text": "Polymorphonuclear leucocytes appeared to be absent .", "annotated_text": "<cell_type>Polymorphonuclear leucocytes</cell_type> appeared to be absent ."}
{"id": "3432", "text": "However , in synovial fluid cell type polymorphonuclear leucocytes were the predominant cell type .", "annotated_text": "However , in <cell_type>synovial fluid cell type polymorphonuclear leucocytes</cell_type> were the predominant cell type ."}
{"id": "3433", "text": "We concluded from this , that one or more of the cell types present in synovial tissue contain a specific steroid receptor , but that this is lacking in synovial fluid polymorphonuclear leucocytes .", "annotated_text": "We concluded from this , that one or more of the cell types present in synovial tissue contain a <protein>specific steroid receptor</protein> , but that this is lacking in <cell_type>synovial fluid polymorphonuclear leucocytes</cell_type> ."}
{"id": "3434", "text": "Clinical implications of glucocorticoid receptors in human leukemia .", "annotated_text": "Clinical implications of <protein>glucocorticoid receptors</protein> in human leukemia ."}
{"id": "3435", "text": "Glucorticoid receptors were studied in various populations of normal human peripheral blood lymphocytes and leukemic lymphoblasts .", "annotated_text": "<protein>Glucorticoid receptors</protein> were studied in various populations of normal <cell_type>human peripheral blood lymphocytes</cell_type> and <cell_type>leukemic lymphoblasts</cell_type> ."}
{"id": "3436", "text": "Normal lymphocytes contain low levels of glucocorticoid receptor ( approximately 2 , 500 sites/cell ) which are identical in T- and non-T-fractions .", "annotated_text": "<cell_type>Normal lymphocytes</cell_type> contain low levels of <protein>glucocorticoid receptor</protein> ( approximately 2 , 500 sites/cell ) which are identical in T- and non-T-fractions ."}
{"id": "3437", "text": "Phytohemagglutinin treatment increases levels about 3-fold .", "annotated_text": "<protein>Phytohemagglutinin</protein> treatment increases levels about 3-fold ."}
{"id": "3438", "text": "Leukemic lymphoblasts contain larger numbers of receptor sites .", "annotated_text": "<cell_type>Leukemic lymphoblasts</cell_type> contain larger numbers of receptor sites ."}
{"id": "3439", "text": "Presence of receptor is correlated with in vitro sensitivitiy to glucocorticoids and in vivo response to therapy .", "annotated_text": "Presence of receptor is correlated with in vitro sensitivitiy to glucocorticoids and in vivo response to therapy ."}
{"id": "3440", "text": "Quantity of receptor is also correlated with complete remission duration independently of leukemic cell type ( T or null ) , initial WBC , or age of patient .", "annotated_text": "Quantity of receptor is also correlated with complete remission duration independently of <cell_type>leukemic cell type</cell_type> ( T or null ) , initial <cell_type>WBC</cell_type> , or age of patient ."}
{"id": "3441", "text": "Quantitative determination of glucocorticoid receptor levels in acute lymphoblastic leukemia may be of value both as an independent prognostic variable and in suggesting which patients should receive glucocorticoid therapy .", "annotated_text": "Quantitative determination of <protein>glucocorticoid receptor</protein> levels in acute lymphoblastic leukemia may be of value both as an independent prognostic variable and in suggesting which patients should receive glucocorticoid therapy ."}
{"id": "3442", "text": "Functional and physical interaction of protein-tyrosine kinases Fyn and Csk in the T-cell signaling system .", "annotated_text": "Functional and physical interaction of <protein>protein-tyrosine kinases Fyn and Csk</protein> in the T-cell signaling system ."}
{"id": "3443", "text": "The Src-like protein-tyrosine kinase Fyn is associated with T-cell antigen receptor .", "annotated_text": "The <protein>Src-like protein-tyrosine kinase</protein> <protein>Fyn</protein> is associated with <protein>T-cell antigen receptor</protein> ."}
{"id": "3444", "text": "Transient expression of actively mutated Fyn , having Phe-528 instead of Tyr-528 or Thr-338 instead of Ile-338 , in Jurkat T-cells stimulated the serum response element ( SRE ) , 12-O-tetradecanoyl-phorbol-13-acetate response element , cyclic AMP response element , and c-fos promoter .", "annotated_text": "Transient expression of actively mutated <protein>Fyn</protein> , having Phe-528 instead of Tyr-528 or Thr-338 instead of Ile-338 , in <cell_type>Jurkat T-cells</cell_type> <dna>stimulated the serum response element</dna> ( <dna>SRE</dna> ) , <dna>12-O-tetradecanoyl-phorbol-13-acetate response element</dna> , <dna>cyclic AMP response element</dna> , and <dna>c-fos promoter</dna> ."}
{"id": "3445", "text": "The stimulation of SRE was particularly prominent not only with active Fyn but also with normal ( wild-type ) Fyn .", "annotated_text": "The stimulation of <dna>SRE</dna> was particularly prominent not only with active <protein>Fyn</protein> but also with <protein>normal ( wild-type ) Fyn</protein> ."}
{"id": "3446", "text": "SRE was also stimulated by both normal and active Lck .", "annotated_text": "<dna>SRE</dna> was also stimulated by both <protein>normal and active Lck</protein> ."}
{"id": "3447", "text": "Furthermore , normal and active Fyn stimulated transcription from the IL-2 gene promoter when transfected cells were stimulated by concanavalin A plus 12-O-tetradecanoylphorbol-13-acetate .", "annotated_text": "Furthermore , <protein>normal and active Fyn</protein> stimulated transcription from the <dna>IL-2 gene promoter</dna> when transfected cells were stimulated by <protein>concanavalin A</protein> plus 12-O-tetradecanoylphorbol-13-acetate ."}
{"id": "3448", "text": "Under the same conditions , Lck did not stimulate IL-2 promoter unless it was activated by mutation .", "annotated_text": "Under the same conditions , <protein>Lck</protein> did not stimulate <dna>IL-2 promoter</dna> unless it was activated by mutation ."}
{"id": "3449", "text": "Interestingly , a mutant Fyn , which has deletions within the SH2 region and so is able to transform chicken embryo fibroblasts , did not stimulate either the c-fos or IL-2 promoter , suggesting the importance of this region in T-cell signaling .", "annotated_text": "Interestingly , a <protein>mutant Fyn</protein> , which has deletions within the <protein>SH2 region</protein> and so is able to transform <cell_type>chicken embryo fibroblasts</cell_type> , did not stimulate either the <dna>c-fos or IL-2 promoter</dna> , suggesting the importance of this region in <cell_type>T-cell</cell_type> signaling ."}
{"id": "3450", "text": "Csk , which phosphorylates tyrosine residues in the negative regulatory sites of Src family kinases , down-regulated Fyn- and Lck-mediated stimulation of the serum response element and Fyn-mediated enhancement of IL-2 promoter activity .", "annotated_text": "<protein>Csk</protein> , which phosphorylates tyrosine residues in the negative regulatory sites of <protein>Src family kinases</protein> , down-regulated Fyn- and Lck-mediated stimulation of the <dna>serum response element</dna> and Fyn-mediated enhancement of <dna>IL-2 promoter</dna> activity ."}
{"id": "3451", "text": "These data suggest that Fyn and Lck , whose activities are regulated by Csk , are involved in different phases of T-cell activation .", "annotated_text": "These data suggest that <protein>Fyn</protein> and <protein>Lck</protein> , whose activities are regulated by <protein>Csk</protein> , are involved in different phases of <cell_type>T-cell</cell_type> activation ."}
{"id": "3452", "text": "A novel NF-kappa B complex containing p65 homodimers : implications for transcriptional control at the level of subunit dimerization .", "annotated_text": "A novel <protein>NF-kappa B complex</protein> containing <protein>p65 homodimers</protein> : implications for transcriptional control at the level of subunit dimerization ."}
{"id": "3453", "text": "The predominant inducible form of the NF-kappa B transcription factor is a heteromeric complex containing two Rel-related DNA-binding subunits , termed p65 and p50 .", "annotated_text": "The predominant inducible form of the <protein>NF-kappa B transcription factor</protein> is a <protein>heteromeric complex</protein> containing two <protein>Rel-related DNA-binding subunits</protein> , <protein>termed p65</protein> and <protein>p50</protein> ."}
{"id": "3454", "text": "Prior transfection studies have shown that when these p65 and p50 subunits are expressed independently as stable homodimers , p65 stimulates kappa B-directed transcription , whereas p50 functions as a kappa B-specific repressor .", "annotated_text": "Prior transfection studies have shown that when these <protein>p65 and p50 subunits</protein> are expressed independently as <protein>stable homodimers</protein> , <protein>p65</protein> stimulates kappa B-directed transcription , whereas <protein>p50</protein> functions as a kappa B-specific repressor ."}
{"id": "3455", "text": "While authentic p50 homodimers ( previously termed KBF1 ) have been detected in nuclear extracts from nontransfected cells , experimental evidence supporting the existence of p65 homodimers in vivo was lacking .", "annotated_text": "While authentic <protein>p50 homodimers</protein> ( previously termed <protein>KBF1</protein> ) have been detected in nuclear extracts from nontransfected cells , experimental evidence supporting the existence of <protein>p65 homodimers</protein> in vivo was lacking ."}
{"id": "3456", "text": "We now provide direct biochemical evidence for the presence of an endogenous pool of inducible p65 homodimers in intact human T cells .", "annotated_text": "We now provide direct biochemical evidence for the presence of an endogenous pool of inducible <protein>p65 homodimers</protein> in intact <cell_type>human T cells</cell_type> ."}
{"id": "3457", "text": "As with the prototypical NF-kappa B p50-p65 heterodimer , this novel p65 homodimeric form of NF-kappa B is functionally sequestered in the cytoplasm but rapidly appears in the nuclear compartment following cellular stimulation .", "annotated_text": "As with the prototypical <protein>NF-kappa B p50-p65 heterodimer</protein> , this novel <protein>p65 homodimeric form</protein> of <protein>NF-kappa B</protein> is functionally sequestered in the cytoplasm but rapidly appears in the nuclear compartment following cellular stimulation ."}
{"id": "3458", "text": "Site-directed mutagenesis studies indicate that the homodimerization function of p65 is dependent upon the presence of cysteine 216 and a conserved recognition motif for protein kinase A ( RRPS ; amino acids 273 to 276 ) , both of which reside within a 91-amino-acid segment of the Rel homology domain that mediates self-association .", "annotated_text": "Site-directed mutagenesis studies indicate that the homodimerization function of <protein>p65</protein> is dependent upon the presence of cysteine 216 and a conserved recognition motif for <protein>protein kinase A</protein> ( <protein>RRPS</protein> ; amino acids 273 to 276 ) , both of which reside within a 91-amino-acid segment of the <protein>Rel homology domain</protein> that mediates self-association ."}
{"id": "3459", "text": "In contrast , mutations at these two sites do not affect heterodimerization of p65 with p50 or its functional interaction with I kappa B alpha .", "annotated_text": "In contrast , mutations at these two sites do not affect heterodimerization of <protein>p65</protein> with <protein>p50</protein> or its functional interaction with I kappa B alpha ."}
{"id": "3460", "text": "These later findings indicate that neither homo- nor heterodimer formation is an absolute prerequisite for I kappa B alpha recognition of p65 .", "annotated_text": "These later findings indicate that neither homo- nor heterodimer formation is an absolute prerequisite for <protein>I kappa B alpha</protein> recognition of <protein>p65</protein> ."}
{"id": "3461", "text": "Taken together with prior in vivo transcription studies , these results suggest that the biological activities of p65 and p50 homodimers are independently regulated , thereby providing an integrated and flexible control mechanism for the rapid activation and repression of NF-kappa B / Rel -directed gene expression .", "annotated_text": "Taken together with prior in vivo transcription studies , these results suggest that the biological activities of <protein>p65 and p50 homodimers</protein> are independently regulated , thereby providing an integrated and flexible control mechanism for the rapid activation and repression of <protein>NF-kappa B</protein> / <protein>Rel</protein> -directed gene expression ."}
{"id": "3462", "text": "Carrier determination for X-linked agammaglobulinemia using X inactivation analysis of purified B cells .", "annotated_text": "Carrier determination for X-linked agammaglobulinemia using X inactivation analysis of <cell_type>purified B cells</cell_type> ."}
{"id": "3463", "text": "We report the development of a relatively quick and simple method for the assessment of X inactivation status for carrier determination in families affected by X-linked agammaglobulinemia ( XLA ) .", "annotated_text": "We report the development of a relatively quick and simple method for the assessment of X inactivation status for carrier determination in families affected by X-linked agammaglobulinemia ( XLA ) ."}
{"id": "3464", "text": "This method utilises an immunomagnetic separation technique for B cell purification and a polymerase chain reaction ( PCR ) based assay for the determination of methylation status at the androgen receptor ( AR ) gene locus to assess whether X inactivation is random or non-random at this locus .", "annotated_text": "This method utilises an immunomagnetic separation technique for <cell_type>B cell</cell_type> purification and a polymerase chain reaction ( PCR ) based assay for the determination of methylation status at the <dna>androgen receptor ( AR ) gene locus</dna> to assess whether X inactivation is random or non-random at this locus ."}
{"id": "3465", "text": "We report the results we have obtained using this assay to investigate females known to be carriers of various X-linked immunodeficiency disorders .", "annotated_text": "We report the results we have obtained using this assay to investigate females known to be carriers of various X-linked immunodeficiency disorders ."}
{"id": "3466", "text": "In addition , we investigated four females from different families affected by XLA , two of whom were of unknown carrier status , and we discuss the results obtained with this and other X-inactivation assays .", "annotated_text": "In addition , we investigated four females from different families affected by XLA , two of whom were of unknown carrier status , and we discuss the results obtained with this and other X-inactivation assays ."}
{"id": "3467", "text": "A similar assay has recently been described by Allen et al. ( 1992 ) and applied to members of one family affected by XLA .", "annotated_text": "A similar assay has recently been described by Allen et al. ( 1992 ) and applied to members of one family affected by XLA ."}
{"id": "3468", "text": "Effects of IL-4 and Fc gamma receptor II engagement on Egr-1 expression during stimulation of B lymphocytes by membrane immunoglobulin crosslinking .", "annotated_text": "Effects of <protein>IL-4</protein> and <protein>Fc gamma receptor II</protein> engagement on <protein>Egr-1</protein> expression during stimulation of <cell_type>B lymphocytes</cell_type> by membrane immunoglobulin crosslinking ."}
{"id": "3469", "text": "Egr-1 is an immediate early gene that is rapidly upregulated in response to mitogenic signals induced by antigen receptor crosslinking on murine B lymphocytes .", "annotated_text": "<dna>Egr-1</dna> is an <dna>immediate early gene</dna> that is rapidly upregulated in response to mitogenic signals induced by antigen receptor crosslinking on <cell_type>murine B lymphocytes</cell_type> ."}
{"id": "3470", "text": "It has been shown that levels of Egr-1 expression are closely correlated with B cell proliferation in several models of B cell activation and tolerance .", "annotated_text": "It has been shown that levels of <dna>Egr-1</dna> expression are closely correlated with <cell_type>B cell</cell_type> proliferation in several models of B cell activation and tolerance ."}
{"id": "3471", "text": "We compared the expression of Egr-1 during B cell stimulation with Fab'2 and IgG anti-immunoglobulin ( anti-Ig ) , since it is known that Fab'2 anti-Ig is mitogenic while IgG anti-Ig is not , owing to a dominant inhibitory effect of crosslinking the B cell Fc gamma RII to membrane Ig .", "annotated_text": "We compared the expression of <dna>Egr-1</dna> during B cell stimulation with <protein>Fab'2</protein> and <protein>IgG anti-immunoglobulin</protein> ( <protein>anti-Ig</protein> ) , since it is known that <protein>Fab'2 anti-Ig</protein> is mitogenic while <protein>IgG anti-Ig</protein> is not , owing to a dominant inhibitory effect of crosslinking the <protein>B cell Fc gamma RII</protein> to <protein>membrane Ig</protein> ."}
{"id": "3472", "text": "While mitogenic doses of Fab'2 anti-Ig induce large and rapid increases in Egr-1 expression , IgG anti-Ig results in smaller increases in Egr-1 mRNA , comparable to that seen with submitogenic concentrations of Fab'2 anti-Ig .", "annotated_text": "While mitogenic doses of <protein>Fab'2 anti-Ig</protein> induce large and rapid increases in Egr-1 expression , <protein>IgG anti-Ig</protein> results in smaller increases in <rna>Egr-1 mRNA</rna> , comparable to that seen with submitogenic concentrations of <protein>Fab'2 anti-Ig</protein> ."}
{"id": "3473", "text": "However , the correlation between Egr-1 expression and B cell proliferation breaks down when IL-4 is added as a co-mitogen to induce B cell proliferation with IgG anti-Ig or submitogenic concentrations of Fab'2 anti-Ig .", "annotated_text": "However , the correlation between Egr-1 expression and B cell proliferation breaks down when <protein>IL-4</protein> is added as a co-mitogen to induce B cell proliferation with <protein>IgG anti-Ig</protein> or submitogenic concentrations of <protein>Fab'2 anti-Ig</protein> ."}
{"id": "3474", "text": "No corresponding increases in Egr-1 mRNA levels are observed when IL-4 is added .", "annotated_text": "No corresponding increases in <rna>Egr-1 mRNA</rna> levels are observed when <protein>IL-4</protein> is added ."}
{"id": "3475", "text": "Therefore , IL-4 overcomes Fc receptor-mediated inhibition of B cell proliferation without affecting inhibition of Egr-1 mRNA induction , as demonstrated earlier for c-myc mRNA in this system .", "annotated_text": "Therefore , <protein>IL-4</protein> overcomes Fc receptor-mediated inhibition of <cell_type>B cell</cell_type> proliferation without affecting inhibition of <rna>Egr-1 mRNA</rna> induction , as demonstrated earlier for <rna>c-myc mRNA</rna> in this system ."}
{"id": "3476", "text": "Identification of a novel cyclosporin-sensitive element in the human tumor necrosis factor alpha gene promoter .", "annotated_text": "Identification of a novel <dna>cyclosporin-sensitive element</dna> in the <dna>human tumor necrosis factor alpha gene promoter</dna> ."}
{"id": "3477", "text": "Tumor necrosis factor alpha ( TNF-alpha ) , a cytokine with pleiotropic biological effects , is produced by a variety of cell types in response to induction by diverse stimuli .", "annotated_text": "<protein>Tumor necrosis factor alpha</protein> ( <protein>TNF-alpha</protein> ) , a <protein>cytokine</protein> with pleiotropic biological effects , is produced by a variety of cell types in response to induction by diverse stimuli ."}
{"id": "3478", "text": "In this paper , TNF-alpha mRNA is shown to be highly induced in a murine T cell clone by stimulation with T cell receptor ( TCR ) ligands or by calcium ionophores alone .", "annotated_text": "In this paper , <rna>TNF-alpha mRNA</rna> is shown to be highly induced in a <cell_line>murine T cell clone</cell_line> by stimulation with <protein>T cell receptor</protein> ( <protein>TCR</protein> ) ligands or by calcium ionophores alone ."}
{"id": "3479", "text": "Induction is rapid , does not require de novo protein synthesis , and is completely blocked by the immunosuppressant cyclosporin A ( CsA ) .", "annotated_text": "Induction is rapid , does not require de novo protein synthesis , and is completely blocked by the immunosuppressant cyclosporin A ( CsA ) ."}
{"id": "3480", "text": "We have identified a human TNF-alpha promoter element , kappa 3 , which plays a key role in the calcium-mediated inducibility and CsA sensitivity of the gene .", "annotated_text": "We have identified a <dna>human TNF-alpha promoter element</dna> , <dna>kappa 3</dna> , which plays a key role in the calcium-mediated inducibility and CsA sensitivity of the gene ."}
{"id": "3481", "text": "In electrophoretic mobility shift assays , an oligonucleotide containing kappa 3 forms two DNA protein complexes with proteins that are present in extracts from unstimulated T cells .", "annotated_text": "In electrophoretic mobility shift assays , an oligonucleotide containing <dna>kappa 3</dna> forms two DNA protein complexes with proteins that are present in extracts from <cell_type>unstimulated T cells</cell_type> ."}
{"id": "3482", "text": "These complexes appear in nuclear extracts only after T cell stimulation .", "annotated_text": "These complexes appear in nuclear extracts only after T cell stimulation ."}
{"id": "3483", "text": "Induction of the inducible nuclear complexes is rapid , independent of protein synthesis , and blocked by CsA , and thus , exactly parallels the induction of TNF-alpha mRNA by TCR ligands or by calcium ionophore .", "annotated_text": "Induction of the inducible <protein>nuclear complexes</protein> is rapid , independent of protein synthesis , and blocked by CsA , and thus , exactly parallels the induction of <rna>TNF-alpha mRNA</rna> by TCR ligands or by calcium ionophore ."}
{"id": "3484", "text": "Our studies indicate that the kappa 3 binding factor resembles the preexisting component of nuclear factor of activated T cells .", "annotated_text": "Our studies indicate that the <protein>kappa 3 binding factor</protein> resembles the preexisting component of <protein>nuclear factor</protein> of <cell_type>activated T cells</cell_type> ."}
{"id": "3485", "text": "Thus , the TNF-alpha gene is an immediate early gene in activated T cells and provides a new model system in which to study CsA-sensitive gene induction in activated T cells .", "annotated_text": "Thus , the <dna>TNF-alpha gene</dna> is an immediate early gene in activated <cell_type>T cells</cell_type> and provides a new model system in which to study <dna>CsA-sensitive gene</dna> induction in <cell_type>activated T cells</cell_type> ."}
{"id": "3486", "text": "Differences in expression of transcription factor AP-1 in human promyelocytic HL-60 cells during differentiation towards macrophages versus granulocytes .", "annotated_text": "Differences in expression of <protein>transcription factor AP-1</protein> in <cell_line>human promyelocytic HL-60 cells</cell_line> during differentiation towards <cell_type>macrophages</cell_type> versus <cell_type>granulocytes</cell_type> ."}
{"id": "3487", "text": "Commitment of HL-60 cells to macrophage or granulocytic differentiation was achieved by incubation with 4 beta-phorbol 12-myristate 13-acetate ( PMA ) for 30-60 min or with dimethyl sulphoxide ( DMSO ) for 24 h respectively .", "annotated_text": "Commitment of <cell_line>HL-60 cells</cell_line> to macrophage or granulocytic differentiation was achieved by incubation with 4 beta-phorbol 12-myristate 13-acetate ( PMA ) for 30-60 min or with dimethyl sulphoxide ( DMSO ) for 24 h respectively ."}
{"id": "3488", "text": "The commitment stage towards PMA-induced macrophage differentiation was associated with increases in jun B and c-fos mRNA levels , as well as with an increase in the binding activity of transcription factor AP-1 .", "annotated_text": "The commitment stage towards PMA-induced macrophage differentiation was associated with increases in jun B and c-fos mRNA levels , as well as with an increase in the binding activity of <protein>transcription factor AP-1</protein> ."}
{"id": "3489", "text": "Nevertheless , gel retardation analysis indicated that the AP-1 activity detected in untreated cells was drastically reduced during the commitment stage of DMSO-induced HL-60 differentiation towards granulocytes .", "annotated_text": "Nevertheless , gel retardation analysis indicated that the <protein>AP-1</protein> activity detected in untreated cells was drastically reduced during the commitment stage of DMSO-induced HL-60 differentiation towards <cell_type>granulocytes</cell_type> ."}
{"id": "3490", "text": "When HL-60 cells were treated with sodium butyrate , which induced monocytic differentiation , a remarkable increase in AP-1 binding activity was detected .", "annotated_text": "When <cell_line>HL-60 cells</cell_line> were treated with sodium butyrate , which induced monocytic differentiation , a remarkable increase in AP-1 binding activity was detected ."}
{"id": "3491", "text": "Treatment of HL-60 cells with 1 alpha , 25-dihydroxyvitamin D3 , another monocytic differentiation agent , induced a weak , but appreciable , increase in AP-1 activity .", "annotated_text": "Treatment of <cell_line>HL-60 cells</cell_line> with 1 alpha , 25-dihydroxyvitamin D3 , another monocytic differentiation agent , induced a weak , but appreciable , increase in <protein>AP-1</protein> activity ."}
{"id": "3492", "text": "Furthermore , addition of sodium butyrate or 1 alpha , 25-dihydroxyvitamin D3 to HL-60 cells induced the expression of c-fos , c-jun , jun B and jun D proto-oncogenes .", "annotated_text": "Furthermore , addition of sodium butyrate or 1 alpha , 25-dihydroxyvitamin D3 to <cell_line>HL-60 cells</cell_line> induced the expression of <dna>c-fos , c-jun , jun B and jun D proto-oncogenes</dna> ."}
{"id": "3493", "text": "In contrast , when HL-60 cells were treated with retinoic acid , a granulocytic differentiation inducer , no enhanced AP-1 binding activity was observed , and only a weak increase in jun D mRNA level was detected .", "annotated_text": "In contrast , when <cell_line>HL-60 cells</cell_line> were treated with retinoic acid , a granulocytic differentiation inducer , no enhanced AP-1 binding activity was observed , and only a weak increase in <rna>jun D mRNA</rna> level was detected ."}
{"id": "3494", "text": "These data indicate that formation of AP-1 is not required for the induction of HL-60 differentiation towards granulocytes , whereas induction of monocytic differentiation is correlated with an increase in AP-1 activity .", "annotated_text": "These data indicate that formation of <protein>AP-1</protein> is not required for the induction of <cell_line>HL-60</cell_line> differentiation towards <cell_type>granulocytes</cell_type> , whereas induction of monocytic differentiation is correlated with an increase in <protein>AP-1</protein> activity ."}
{"id": "3495", "text": "The differential expression of AP-1 activity may be critical in the differentiation of HL-60 cells towards monocytic or granulocytic lineages", "annotated_text": "The differential expression of <protein>AP-1</protein> activity may be critical in the differentiation of <cell_line>HL-60 cells</cell_line> towards <cell_type>monocytic or granulocytic lineages</cell_type>"}
{"id": "3496", "text": "Glucocorticoid receptors and sensitivity in leukemias .", "annotated_text": "<protein>Glucocorticoid receptors</protein> and sensitivity in leukemias ."}
{"id": "3497", "text": "In an attempt to investigate the utility of glucocorticoid receptor determination to predict clinical responsiveness in human leukemias we have studied glucocorticoid receptors in the leukemic cells from 46 patients and in the lymphocytes from 18 normal donors .", "annotated_text": "In an attempt to investigate the utility of <protein>glucocorticoid receptor</protein> determination to predict clinical responsiveness in human leukemias we have studied <protein>glucocorticoid receptors</protein> in the <cell_type>leukemic cells</cell_type> from 46 patients and in the <cell_type>lymphocytes</cell_type> from 18 normal donors ."}
{"id": "3498", "text": "In the normal lymphocytes there were 3 , 875 ( Median ) specific binding sites per cell .", "annotated_text": "In the <cell_type>normal lymphocytes</cell_type> there were 3 , 875 ( Median ) specific binding sites per cell ."}
{"id": "3499", "text": "The blasts from 17 patients with ANLL had on average higher levels of binding sites per cell ( Median = 7 , 250 , range : 0 to 15 , 295 ) than the other leukemias .", "annotated_text": "The <cell_type>blasts</cell_type> from 17 patients with ANLL had on average higher levels of <protein>binding sites</protein> per cell ( Median = 7 , 250 , range : 0 to 15 , 295 ) than the other leukemias ."}
{"id": "3500", "text": "Of the 15 patients with CLL , six had received glucocorticoid treatment for 3 to 5 years .", "annotated_text": "Of the 15 patients with CLL , six had received glucocorticoid treatment for 3 to 5 years ."}
{"id": "3501", "text": "Their lymphocytes had lower number of receptors ( Median = 2 , 000 ) than the other cases which were newly diagnosed ( Median = 4 , 500 ) .", "annotated_text": "Their <cell_type>lymphocytes</cell_type> had lower number of receptors ( Median = 2 , 000 ) than the other cases which were newly diagnosed ( Median = 4 , 500 ) ."}
{"id": "3502", "text": "Four patients had ALL/AUL , three patients had blast crisis as terminal phase of CML , and seven had leukemic Non-Hodgkin lymphomas ( Median = 3 , 500 sites/cell ) .", "annotated_text": "Four patients had ALL/AUL , three patients had blast crisis as terminal phase of CML , and seven had leukemic Non-Hodgkin lymphomas ( Median = 3 , 500 sites/cell ) ."}
{"id": "3503", "text": "In 24 patients we have also studied the in vitro sensitivity of the leukemic cells to dexamethasone .", "annotated_text": "In 24 patients we have also studied the in vitro sensitivity of the <cell_type>leukemic cells</cell_type> to dexamethasone ."}
{"id": "3504", "text": "There was no marked correlation between glucocorticoid receptor levels and in vitro sensitivity .", "annotated_text": "There was no marked correlation between <protein>glucocorticoid receptor</protein> levels and in vitro sensitivity ."}
{"id": "3505", "text": "An attempt to correlate receptor levels with clinical responsiveness demonstrated that glucocorticoid receptor determination might be of value in patients with lymphoid malignancies but probably not in patients with other leukemias .", "annotated_text": "An attempt to correlate receptor levels with clinical responsiveness demonstrated that <protein>glucocorticoid receptor</protein> determination might be of value in patients with lymphoid malignancies but probably not in patients with other leukemias ."}
{"id": "3506", "text": "'Activation-labile ' glucocorticoid-receptor complexes of a steroid-resistant variant of CEM-C7 human lymphoid cells .", "annotated_text": "<protein>'Activation-labile ' glucocorticoid-receptor complexes</protein> of a steroid-resistant variant of <cell_line>CEM-C7 human lymphoid cells</cell_line> ."}
{"id": "3507", "text": "For cytoplasmic glucocorticoid-receptor complexes to enter and accumulate in the nucleus a temperature-dependent event , 'activation ' is required .", "annotated_text": "For <protein>cytoplasmic glucocorticoid-receptor complexes</protein> to enter and accumulate in the nucleus a temperature-dependent event , 'activation ' is required ."}
{"id": "3508", "text": "Activation can be achieved in vitro by increased ionic strength , dilution or gel filtration and is manifested by an increased affinity of steroid-receptor complex for DNA and an altered elution profile from ion-exchange resins .", "annotated_text": "Activation can be achieved in vitro by increased ionic strength , dilution or gel filtration and is manifested by an increased affinity of <protein>steroid-receptor complex</protein> for <dna>DNA</dna> and an altered elution profile from ion-exchange resins ."}
{"id": "3509", "text": "Munck and Foley have shown that activated complexes isolated from thymocytes elute from DEAE-cellulose in a manner identical to complexes activated in vitro .", "annotated_text": "Munck and Foley have shown that <protein>activated complexes</protein> isolated from thymocytes elute from DEAE-cellulose in a manner identical to complexes activated in vitro ."}
{"id": "3510", "text": "We report here that DEAE-cellulose chromatography of steroid-receptor complexes from CEM-C7 , a cloned human leukaemic T-cell line sensitive to the cytolytic action of glucocorticoids , and its steroid-resistant subclone 4R4 demonstrated that steroid receptors of clone 4R4 can not form stable activated complexes .", "annotated_text": "We report here that DEAE-cellulose chromatography of <protein>steroid-receptor complexes</protein> from <cell_line>CEM-C7</cell_line> , a <cell_line>cloned human leukaemic T-cell line</cell_line> sensitive to the cytolytic action of glucocorticoids , and its <cell_line>steroid-resistant subclone 4R4</cell_line> demonstrated that <protein>steroid receptors</protein> of <cell_line>clone 4R4</cell_line> can not form stable activated complexes ."}
{"id": "3511", "text": "This defines a new defect in receptor action , activation lability ( r+act1 ) , which is unlike either the r- , r+nt- , or r+nti phenotypes previously described for mouse lymphoid variants .", "annotated_text": "This defines a new defect in receptor action , activation lability ( r+act1 ) , which is unlike either the <cell_line>r- , r+nt- , or r+nti phenotypes</cell_line> previously described for <cell_line>mouse lymphoid variants</cell_line> ."}
{"id": "3512", "text": "Granulocytes in the endometrium of post-partum women .", "annotated_text": "<cell_type>Granulocytes</cell_type> in the endometrium of post-partum women ."}
{"id": "3513", "text": "Endometrial samples of women at various stages of gonadal activity after parturition were examined for the presence and numbers of endometrial granulocytes .", "annotated_text": "Endometrial samples of women at various stages of gonadal activity after parturition were examined for the presence and numbers of <cell_type>endometrial granulocytes</cell_type> ."}
{"id": "3514", "text": "Although samples at all the stages contained significant numbers of the granulocytes ( i.e. greater than 7/high-power field ) , the 100 % values for late-proliferative and adaptation hyperplasia were significantly higher than the values for the resting ( 81.8 % ) , early ( 82.4 % ) and mid- ( 87.9 % ) proliferative and secretory ( 83.3 % ) phases .", "annotated_text": "Although samples at all the stages contained significant numbers of the <cell_type>granulocytes</cell_type> ( i.e. greater than 7/high-power field ) , the 100 % values for late-proliferative and adaptation hyperplasia were significantly higher than the values for the resting ( 81.8 % ) , early ( 82.4 % ) and mid- ( 87.9 % ) proliferative and secretory ( 83.3 % ) phases ."}
{"id": "3515", "text": "We suggest that this correlates with the suggestion that the granulocytes constitute a receptor system for oestrogens .", "annotated_text": "We suggest that this correlates with the suggestion that the <cell_type>granulocytes</cell_type> constitute a receptor system for oestrogens ."}
{"id": "3516", "text": "Interaction of glucocorticoids with macrophages .", "annotated_text": "Interaction of glucocorticoids with <cell_type>macrophages</cell_type> ."}
{"id": "3517", "text": "Identification of glucocorticoid receptors in monocytes and macrophages .", "annotated_text": "Identification of <protein>glucocorticoid receptors</protein> in <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> ."}
{"id": "3518", "text": "Glucocorticoid binding was measured in resident and thioglycollate-elicited mouse peritoneal macrophages , rabbit alveolar macrophages , and human monocytes .", "annotated_text": "Glucocorticoid binding was measured in resident and <cell_type>thioglycollate-elicited mouse peritoneal macrophages</cell_type> , <cell_type>rabbit alveolar macrophages</cell_type> , and <cell_type>human monocytes</cell_type> ."}
{"id": "3519", "text": "Two assays of binding were used -- an assay with intact cells in suspension or monolayers , and an assay of cytosol and nuclear forms of glucocorticoid receptors .", "annotated_text": "Two assays of binding were used -- an assay with <cell_type>intact cells</cell_type> in suspension or monolayers , and an assay of cytosol and nuclear forms of <protein>glucocorticoid receptors</protein> ."}
{"id": "3520", "text": "The mononuclear phagocytes contained approximately equal to 4 -- 10 X 10 ( 3 ) high affinity receptor sites per cell , with dissociation constants of approximately equal to 2 -- 8 nM dexamethasone .", "annotated_text": "The <cell_type>mononuclear phagocytes</cell_type> contained approximately equal to 4 -- 10 X 10 ( 3 ) <protein>high affinity receptor sites</protein> per cell , with dissociation constants of approximately equal to 2 -- 8 nM dexamethasone ."}
{"id": "3521", "text": "The binding to the saturable sites was specific for steroids with glucocorticoid or antiglucocorticoid activity .", "annotated_text": "The binding to the <protein>saturable sites</protein> was specific for steroids with glucocorticoid or antiglucocorticoid activity ."}
{"id": "3522", "text": "Cortisol , corticosterone , and progesterone competed with dexamethasone for binding , whereas estradiol , dihydrotestosterone , and 11-epicortisol competed very little .", "annotated_text": "Cortisol , corticosterone , and progesterone competed with dexamethasone for binding , whereas estradiol , dihydrotestosterone , and 11-epicortisol competed very little ."}
{"id": "3523", "text": "Binding of dexamethasone to cytosol and nuclear forms of the receptor complex and temperature-sensitive translocation of cytosol forms to nuclear forms were shown .", "annotated_text": "Binding of dexamethasone to cytosol and nuclear forms of the <protein>receptor complex</protein> and temperature-sensitive translocation of cytosol forms to nuclear forms were shown ."}
{"id": "3524", "text": "At 37 degrees C the predominant form of the hormone-receptor complex was nuclear .", "annotated_text": "At 37 degrees C the predominant form of the <protein>hormone-receptor complex</protein> was nuclear ."}
{"id": "3525", "text": "These results demonstrate that corticosteroids interact with macrophages at physiological concentrations .", "annotated_text": "These results demonstrate that corticosteroids interact with <cell_type>macrophages</cell_type> at physiological concentrations ."}
{"id": "3526", "text": "Nitric oxide signaling : a possible role for G proteins .", "annotated_text": "Nitric oxide signaling : a possible role for <protein>G proteins</protein> ."}
{"id": "3527", "text": "We have previously reported various inductive effects of nitric oxide on human PBMC .", "annotated_text": "We have previously reported various inductive effects of nitric oxide on <cell_type>human PBMC</cell_type> ."}
{"id": "3528", "text": "We describe a novel and potentially important mechanism of nitric oxide signaling-through direct activation of guanine nucleotide-binding proteins ( G proteins ) .", "annotated_text": "We describe a novel and potentially important mechanism of nitric oxide signaling-through direct activation of <protein>guanine nucleotide-binding proteins</protein> ( <protein>G proteins</protein> ) ."}
{"id": "3529", "text": "We have found that nitric oxide treatment of membranes isolated from fresh human PBMC enhances the ability of these membranes to hydrolyze [ gamma-32P ] GTP and bind [ gamma-35S ] GTP .", "annotated_text": "We have found that nitric oxide treatment of membranes isolated from <cell_type>fresh human PBMC</cell_type> enhances the ability of these membranes to hydrolyze [ gamma-32P ] GTP and bind [ gamma-35S ] GTP ."}
{"id": "3530", "text": "In addition , treatment of whole cells with nitric oxide yielded membranes with enhanced GTPase activity .", "annotated_text": "In addition , treatment of whole cells with nitric oxide yielded membranes with enhanced GTPase activity ."}
{"id": "3531", "text": "Furthermore , the GTPase activity of pure , recombinant Gs alpha , Gi alpha 1 , and p21ras was greatly enhanced by nitric oxide .", "annotated_text": "Furthermore , the GTPase activity of pure , recombinant <protein>Gs alpha</protein> , <protein>Gi alpha 1</protein> , and <protein>p21ras</protein> was greatly enhanced by nitric oxide ."}
{"id": "3532", "text": "In support of the existence of this pathway in whole cells , we found that the G protein inhibitor , GDP-beta-S , blocked NF-kappa B translocation induced by nitric oxide or LPS in permeabilized cells .", "annotated_text": "In support of the existence of this pathway in whole cells , we found that the G protein inhibitor , GDP-beta-S , blocked <protein>NF-kappa B</protein> translocation induced by nitric oxide or LPS in <cell_type>permeabilized cells</cell_type> ."}
{"id": "3533", "text": "In addition , nitric oxide greatly reduced the pertussis toxin-mediated ADP-ribosylation of 45- and 41-kDa proteins in membranes of these cells .", "annotated_text": "In addition , nitric oxide greatly reduced the pertussis toxin-mediated ADP-ribosylation of <protein>45- and 41-kDa proteins</protein> in membranes of these cells ."}
{"id": "3534", "text": "Because G proteins play a central role in many diverse signaling systems , activation by an endogenous and inducible oxidant may represent a novel signaling pathway .", "annotated_text": "Because <protein>G proteins</protein> play a central role in many diverse signaling systems , activation by an endogenous and inducible oxidant may represent a novel signaling pathway ."}
{"id": "3535", "text": "The granulocyte-macrophage colony-stimulating factor promoter cis-acting element CLE0 mediates induction signals in T cells and is recognized by factors related to AP1 and NFAT .", "annotated_text": "The <dna>granulocyte-macrophage colony-stimulating factor promoter cis-acting element</dna> <dna>CLE0</dna> mediates induction signals in <cell_type>T cells</cell_type> and is recognized by factors related to <protein>AP1</protein> and <protein>NFAT</protein> ."}
{"id": "3536", "text": "Expression of the granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene in T cells is activated by the combination of phorbol ester ( phorbol myristate acetate ) and calcium ionophore ( A23187 ) , which mimic antigen stimulation through the T-cell receptor .", "annotated_text": "Expression of the <dna>granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene</dna> in T cells is activated by the combination of phorbol ester ( phorbol myristate acetate ) and calcium ionophore ( A23187 ) , which mimic antigen stimulation through the <protein>T-cell receptor</protein> ."}
{"id": "3537", "text": "We have previously shown that a fragment containing bp -95 to +27 of the mouse GM-CSF promoter can confer inducibility to reporter genes in the human Jurkat T-cell line .", "annotated_text": "We have previously shown that a fragment containing <dna>bp -95 to +27</dna> of the <dna>mouse GM-CSF promoter</dna> can confer inducibility to <dna>reporter genes</dna> in the <cell_line>human Jurkat T-cell line</cell_line> ."}
{"id": "3538", "text": "Here we use an in vitro transcription system to demonstrate that a cis-acting element ( positions -54 to -40 ) , referred to as CLE0 , is a target for the induction signals .", "annotated_text": "Here we use an in vitro transcription system to demonstrate that a <dna>cis-acting element</dna> ( <dna>positions -54 to -40</dna> ) , referred to as <dna>CLE0</dna> , is a target for the induction signals ."}
{"id": "3539", "text": "We observed induction with templates containing intact CLE0 but not with templates with deleted or mutated CLE0 .", "annotated_text": "We observed induction with templates containing intact <dna>CLE0</dna> but not with templates with <dna>deleted or mutated CLE0</dna> ."}
{"id": "3540", "text": "We also observed that two distinct signals were required for the stimulation through CLE0 , since only extracts from cells treated with both phorbol myristate acetate and A23187 supported optimal induction .", "annotated_text": "We also observed that two distinct signals were required for the stimulation through <dna>CLE0</dna> , since only extracts from cells treated with both phorbol myristate acetate and A23187 supported optimal induction ."}
{"id": "3541", "text": "Stimulation probably was mediated by CLE0-binding proteins because depletion of these proteins specifically reduced GM-CSF transcription .", "annotated_text": "Stimulation probably was mediated by <protein>CLE0-binding proteins</protein> because depletion of these proteins specifically reduced <protein>GM-CSF</protein> transcription ."}
{"id": "3542", "text": "One of the binding factors possessed biochemical and immunological features identical to those of the transcription factor AP1 .", "annotated_text": "One of the <protein>binding factors</protein> possessed biochemical and immunological features identical to those of the <protein>transcription factor AP1</protein> ."}
{"id": "3543", "text": "Another factor resembled the T-cell-specific factor NFAT .", "annotated_text": "Another factor resembled the <protein>T-cell-specific factor NFAT</protein> ."}
{"id": "3544", "text": "The characteristics of these two factors are consistent with their involvement in GM-CSF induction .", "annotated_text": "The characteristics of these two factors are consistent with their involvement in GM-CSF induction ."}
{"id": "3545", "text": "The presence of CLE0-like elements in the promoters of interleukin-3 ( IL-3 ) , IL-4 , IL-5 , GM-CSF , and NFAT sites in the IL-2 promoter suggests that the factors we detected , or related factors that recognize these sites , may account for the coordinate induction of these genes during T-cell activation .", "annotated_text": "The presence of <dna>CLE0-like elements</dna> in the <dna>promoters</dna> of <dna>interleukin-3 ( IL-3 ) , IL-4 , IL-5 , GM-CSF , and NFAT sites</dna> in the <dna>IL-2 promoter</dna> suggests that the factors we detected , or related factors that recognize these sites , may account for the coordinate induction of these genes during <cell_type>T-cell</cell_type> activation ."}
{"id": "3546", "text": "Identification and characterization of an Alu-containing , T-cell-specific enhancer located in the last intron of the human CD8 alpha gene .", "annotated_text": "Identification and characterization of an <dna>Alu-containing , T-cell-specific enhancer</dna> located in the last <dna>intron</dna> of the <dna>human CD8 alpha gene</dna> ."}
{"id": "3547", "text": "Expression of the human CD8 alpha gene is restricted to cells of the lymphoid lineage and developmentally regulated during thymopoiesis .", "annotated_text": "Expression of the <dna>human CD8 alpha gene</dna> is restricted to cells of the <cell_type>lymphoid lineage</cell_type> and developmentally regulated during thymopoiesis ."}
{"id": "3548", "text": "As an initial step towards understanding the molecular basis for tissue-specific expression of this gene , we surveyed the surrounding chromatin structure for potential cis-acting regulatory regions by DNase I hypersensitivity mapping and found four hypersensitive sites , three of which were T cell restricted .", "annotated_text": "As an initial step towards understanding the molecular basis for tissue-specific expression of this gene , we surveyed the surrounding chromatin structure for potential <dna>cis-acting regulatory regions</dna> by <protein>DNase I</protein> hypersensitivity mapping and found four hypersensitive sites , three of which were T cell restricted ."}
{"id": "3549", "text": "By using a reporter-based expression approach , a T-cell-specific enhancer was identified by its close association with a prominent T-cell-restricted hypersensitive sites in the last intron of the CD8 alpha gene .", "annotated_text": "By using a reporter-based expression approach , a <dna>T-cell-specific enhancer</dna> was identified by its close association with a prominent <dna>T-cell-restricted hypersensitive sites</dna> in the last intron of the <dna>CD8 alpha gene</dna> ."}
{"id": "3550", "text": "Deletion studies demonstrated that the minimal enhancer is adjacent to a negative regulatory element .", "annotated_text": "Deletion studies demonstrated that the minimal enhancer is adjacent to a negative regulatory element ."}
{"id": "3551", "text": "DNA sequence analysis of the minimal enhancer revealed a striking cluster of consensus binding sites for Ets-1 , TCF-1 , CRE , GATA-3 , LyF-1 , and bHLH proteins which were verified by electrophoretic mobility shift assays .", "annotated_text": "DNA sequence analysis of the <dna>minimal enhancer</dna> revealed a striking cluster of <dna>consensus binding sites</dna> for <protein>Ets-1 , TCF-1 , CRE , GATA-3 , LyF-1 , and bHLH proteins</protein> which were verified by electrophoretic mobility shift assays ."}
{"id": "3552", "text": "In addition , the 5 ' end of the enhancer was composed of an Alu repeat which contained the GATA-3 , bHLH , and LyF-1 binding sites .", "annotated_text": "In addition , the <dna>5 ' end</dna> of the <dna>enhancer</dna> was composed of an Alu repeat which contained the <dna>GATA-3 , bHLH , and LyF-1 binding sites</dna> ."}
{"id": "3553", "text": "Site-directed mutation of the Ets-1 and GATA-3 sites dramatically reduced enhancer activity .", "annotated_text": "Site-directed mutation of the <dna>Ets-1 and GATA-3 sites</dna> dramatically reduced enhancer activity ."}
{"id": "3554", "text": "The functional importance of the other binding sites only became apparent when combinations of mutations were analyzed .", "annotated_text": "The functional importance of the other binding sites only became apparent when combinations of mutations were analyzed ."}
{"id": "3555", "text": "Taken together , these results suggest that the human CD8 alpha gene is regulated by the interaction of multiple T-cell nuclear proteins with a transcriptional enhancer located in the last intron of the gene .", "annotated_text": "Taken together , these results suggest that the <dna>human CD8 alpha gene</dna> is regulated by the interaction of multiple <protein>T-cell nuclear proteins</protein> with a transcriptional enhancer located in the last <dna>intron</dna> of the gene ."}
{"id": "3556", "text": "Comparison of the CD8 alpha enhancer with other recently identified T-cell-specific regulatory elements suggests that a common set of transcription factors regulates several T-cell genes .", "annotated_text": "Comparison of the <dna>CD8 alpha enhancer</dna> with other recently identified <dna>T-cell-specific regulatory elements</dna> suggests that a common set of <protein>transcription factors</protein> regulates several <dna>T-cell genes</dna> ."}
{"id": "3557", "text": "Molecular regulation of the human IL-3 gene : inducible T cell-restricted expression requires intact AP-1 and Elf-1 nuclear protein binding sites .", "annotated_text": "Molecular regulation of the <dna>human IL-3 gene</dna> : inducible T cell-restricted expression requires intact <dna>AP-1 and Elf-1 nuclear protein binding sites</dna> ."}
{"id": "3558", "text": "Interleukin 3 ( IL-3 ) is a hematopoietic stem-cell growth and differentiation factor that is expressed solely in activated T and NK cells .", "annotated_text": "<protein>Interleukin 3</protein> ( <protein>IL-3</protein> ) is a <protein>hematopoietic stem-cell growth and differentiation factor</protein> that is expressed solely in activated <cell_type>T and NK cells</cell_type> ."}
{"id": "3559", "text": "Studies to date have identified elements 5 ' to the IL-3 coding sequences that regulate its transcription , but the sequences that confer T cell-specific expression remain to be clearly defined .", "annotated_text": "Studies to date have identified elements 5 ' to the <dna>IL-3 coding sequences</dna> that regulate its transcription , but the sequences that confer T cell-specific expression remain to be clearly defined ."}
{"id": "3560", "text": "We have now identified DNA sequences that are required for T cell-restricted IL-3 gene transcription .", "annotated_text": "We have now identified <dna>DNA sequences</dna> that are required for T cell-restricted <dna>IL-3 gene</dna> transcription ."}
{"id": "3561", "text": "A series of transient transfections performed with human IL-3-chloramphenicol acetyltransferase ( CAT ) reporter plasmids in T and non-T cells revealed that a plasmid containing 319 bp of 5 ' flanking sequences was active exclusively in T cells .", "annotated_text": "A series of transient transfections performed with <dna>human IL-3-chloramphenicol acetyltransferase ( CAT ) reporter plasmids</dna> in <cell_type>T and non-T cells</cell_type> revealed that a <dna>plasmid</dna> containing 319 bp of <dna>5 ' flanking sequences</dna> was active exclusively in <cell_type>T cells</cell_type> ."}
{"id": "3562", "text": "Deletion analysis revealed that T cell specificity was conferred by a 49-bp fragment ( bp -319 to -270 ) that included a potential binding site for AP-1 transcription factors 6 bp upstream of a binding site for Elf-1 , a member of the Ets family of transcription factors .", "annotated_text": "Deletion analysis revealed that <cell_type>T cell</cell_type> specificity was conferred by a <dna>49-bp fragment</dna> ( <dna>bp -319 to -270</dna> ) that included a <dna>potential binding site</dna> for <protein>AP-1 transcription factors</protein> 6 bp upstream of a <dna>binding site for Elf-1</dna> , a member of the <protein>Ets family</protein> of <protein>transcription factors</protein> ."}
{"id": "3563", "text": "DNaseI footprint and electrophoretic mobility shift assay analyses performed with MLA-144 T cell nuclear extracts demonstrated that this 49-bp region contains a nuclear protein binding region that includes consensus AP-1 and Elf-1 binding sites .", "annotated_text": "<protein>DNaseI</protein> footprint and electrophoretic mobility shift assay analyses performed with <cell_line>MLA-144 T cell</cell_line> nuclear extracts demonstrated that this <dna>49-bp region</dna> contains a <dna>nuclear protein binding region</dna> that includes <dna>consensus AP-1 and Elf-1 binding sites</dna> ."}
{"id": "3564", "text": "In addition , extracts prepared from purified human T cells contained proteins that bound to synthetic oligonucleotides corresponding to the AP-1 and Elf-1 binding sites .", "annotated_text": "In addition , extracts prepared from <cell_type>purified human T cells</cell_type> contained proteins that bound to synthetic oligonucleotides corresponding to the <dna>AP-1 and Elf-1 binding sites</dna> ."}
{"id": "3565", "text": "In vitro-transcribed and -translated Elf-1 protein bound specifically to the Elf-1 site , and Elf-1 antisera competed and super shifted nuclear protein complexes present in MLA-144 nuclear extracts .", "annotated_text": "In vitro-transcribed and -translated <protein>Elf-1 protein</protein> bound specifically to the <dna>Elf-1 site</dna> , and Elf-1 antisera competed and super shifted nuclear protein complexes present in <cell_line>MLA-144</cell_line> nuclear extracts ."}
{"id": "3566", "text": "Moreover , addition of anti-Jun family antiserum in electrophoretic mobility shift assay reactions completely blocked formation of the AP-1-related complexes .", "annotated_text": "Moreover , addition of anti-Jun family antiserum in electrophoretic mobility shift assay reactions completely blocked formation of the <protein>AP-1-related complexes</protein> ."}
{"id": "3567", "text": "Transient transfection studies in MLA-144 T cells revealed that constructs containing mutations in the AP-1 site almost completely abolished CAT activity while mutation of the Elf-1 site or the NF-IL-3 site , a previously described nuclear protein binding site ( bp. -155 to -148 ) in the IL-3 promoter , reduced CAT activity to < 25 % of the activity given by wild-type constructs .", "annotated_text": "Transient transfection studies in <cell_line>MLA-144 T cells</cell_line> revealed that constructs containing mutations in the <dna>AP-1 site</dna> almost completely abolished CAT activity while mutation of the <dna>Elf-1 site</dna> or the <dna>NF-IL-3 site</dna> , a previously described <dna>nuclear protein binding site</dna> ( <dna>bp. -155 to -148</dna> ) in the <dna>IL-3 promoter</dna> , reduced CAT activity to < 25 % of the activity given by wild-type constructs ."}
{"id": "3568", "text": "We conclude that expression of the human IL-3 gene requires the AP-1 and Elf-1 binding sites ; however , unlike other previously characterized cytokine genes such as IL-2 , the AP-1 and Elf-1 factors can bind independently in the IL-3 gene .", "annotated_text": "We conclude that expression of the <dna>human IL-3 gene</dna> requires the <dna>AP-1 and Elf-1 binding sites</dna> ; however , unlike other previously characterized <dna>cytokine genes</dna> such as <protein>IL-2</protein> , the <protein>AP-1 and Elf-1 factors</protein> can bind independently in the <dna>IL-3 gene</dna> ."}
{"id": "3569", "text": "( ABSTRACT TRUNCATED AT 400 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 400 WORDS )"}
{"id": "3570", "text": "Combination IL-2 and IL-4 reduces glucocorticoid receptor-binding affinity and T cell response to glucocorticoids .", "annotated_text": "Combination <protein>IL-2</protein> and <protein>IL-4</protein> reduces glucocorticoid receptor-binding affinity and <cell_type>T cell</cell_type> response to glucocorticoids ."}
{"id": "3571", "text": "The mechanisms contributing to persistent T cell activation and poor response to glucocorticoids in chronic inflammatory illnesses such as steroid resistant ( SR ) asthma are poorly defined .", "annotated_text": "The mechanisms contributing to persistent <cell_type>T cell</cell_type> activation and poor response to glucocorticoids in chronic inflammatory illnesses such as steroid resistant ( SR ) asthma are poorly defined ."}
{"id": "3572", "text": "We examined the possibility that certain cytokines , specifically IL-2 and IL-4 , could affect T cell response to glucocorticoids .", "annotated_text": "We examined the possibility that certain cytokines , specifically <protein>IL-2</protein> and <protein>IL-4</protein> , could affect T cell response to glucocorticoids ."}
{"id": "3573", "text": "A [ 3H ] dexamethasone radioligand-binding assay was used to measure the number of glucocorticoid receptors ( GR ) and dissociation constant ( Kd ) in PBMC from normal donors and patients with SR asthma , cultured in the absence and presence of these cytokines .", "annotated_text": "A [ 3H ] dexamethasone radioligand-binding assay was used to measure the number of <protein>glucocorticoid receptors</protein> ( <protein>GR</protein> ) and dissociation constant ( Kd ) in <cell_type>PBMC</cell_type> from normal donors and patients with SR asthma , cultured in the absence and presence of these <protein>cytokines</protein> ."}
{"id": "3574", "text": "PBMC from normal donors incubated for 48 h in the presence of combination IL-2 + IL-4 had nuclear GR with significantly reduced binding affinity ( GR Kd = 36.1 +/- 1.63 nM , mean +/- SEM ; p = 0.0001 ) as compared with PBMC incubated with medium alone ( GR Kd = 6.74 +/- 0.46 nM ) .", "annotated_text": "PBMC from normal donors incubated for 48 h in the presence of combination <protein>IL-2</protein> + <protein>IL-4</protein> had nuclear GR with significantly reduced binding affinity ( GR Kd = 36.1 +/- 1.63 nM , mean +/- SEM ; p = 0.0001 ) as compared with <cell_type>PBMC</cell_type> incubated with medium alone ( GR Kd = 6.74 +/- 0.46 nM ) ."}
{"id": "3575", "text": "The cytosolic GR Kd remained unchanged .", "annotated_text": "The cytosolic GR Kd remained unchanged ."}
{"id": "3576", "text": "However , when PBMC were incubated with IL-2 alone or IL-4 alone , no change in GR-binding affinity was observed .", "annotated_text": "However , when <cell_type>PBMC</cell_type> were incubated with <protein>IL-2</protein> alone or <protein>IL-4</protein> alone , no change in GR-binding affinity was observed ."}
{"id": "3577", "text": "Furthermore , when T cells and non-T cells were individually stimulated with combination IL-2 + IL-4 , a significant reduction in GR-binding affinity was observed only in the T cell population ( p = 0.0001 ) .", "annotated_text": "Furthermore , when <cell_type>T cells</cell_type> and <cell_type>non-T cells</cell_type> were individually stimulated with combination IL-2 + IL-4 , a significant reduction in GR-binding affinity was observed only in the <cell_type>T cell population</cell_type> ( p = 0.0001 ) ."}
{"id": "3578", "text": "The IL-2 + IL-4-induced alteration in PBMC GR Kd was associated with an increase in GR number ( 8348 +/- 964 vs 1710 +/- 228 sites/cell ; p = 0.0003 ) .", "annotated_text": "The IL-2 + IL-4-induced alteration in PBMC GR Kd was associated with an increase in GR number ( 8348 +/- 964 vs 1710 +/- 228 sites/cell ; p = 0.0003 ) ."}
{"id": "3579", "text": "More importantly , the alteration in PBMC GR-binding affinity with IL-2 + IL-4 was associated with a functional change in T cell response to methylprednisolone MPN , i.e. , a reduced inhibitory effect of MPN on PMA/ionomycin-induced T cell proliferation .", "annotated_text": "More importantly , the alteration in PBMC GR-binding affinity with <protein>IL-2</protein> + <protein>IL-4</protein> was associated with a functional change in T cell response to methylprednisolone MPN , i.e. , a reduced inhibitory effect of MPN on PMA/ionomycin-induced <cell_type>T cell</cell_type> proliferation ."}
{"id": "3580", "text": "These effects of IL-2 + IL-4 on PBMC GR affinity and response to MPN were blocked by co-incubation with IFN-gamma .", "annotated_text": "These effects of <protein>IL-2</protein> + <protein>IL-4</protein> on <cell_type>PBMC</cell_type> <protein>GR</protein> affinity and response to MPN were blocked by co-incubation with <protein>IFN-gamma</protein> ."}
{"id": "3581", "text": "Freshly isolated PBMC from four patients with SR asthma had a significantly reduced GR-binding affinity ( Kd = 40.0 +/- 2.68 nM ; p = 0.0001 ) when compared with seven normal subjects ( 7.15 +/- 0.41 nM ) .", "annotated_text": "Freshly isolated <cell_type>PBMC</cell_type> from four patients with SR asthma had a significantly reduced GR-binding affinity ( Kd = 40.0 +/- 2.68 nM ; p = 0.0001 ) when compared with seven normal subjects ( 7.15 +/- 0.41 nM ) ."}
{"id": "3582", "text": "The altered PBMC GR binding from patients with SR asthma reversed to normal when incubated with medium alone , but was sustained with IL-2 + IL-4 .", "annotated_text": "The altered PBMC GR binding from patients with SR asthma reversed to normal when incubated with medium alone , but was sustained with <protein>IL-2</protein> + <protein>IL-4</protein> ."}
{"id": "3583", "text": "These observations suggest that with persistent inflammation certain cytokines may contribute to an impaired response to glucocorticoids .", "annotated_text": "These observations suggest that with persistent inflammation certain <protein>cytokines</protein> may contribute to an impaired response to glucocorticoids ."}
{"id": "3584", "text": "Furthermore , the effects of IL-2 and IL-4 were blocked by IFN-gamma .", "annotated_text": "Furthermore , the effects of <protein>IL-2</protein> and <protein>IL-4</protein> were blocked by <protein>IFN-gamma</protein> ."}
{"id": "3585", "text": "Characterization of the human CD4 gene promoter : transcription from the CD4 gene core promoter is tissue-specific and is activated by Ets proteins .", "annotated_text": "Characterization of the <dna>human CD4 gene promoter</dna> : transcription from the <dna>CD4 gene core promoter</dna> is tissue-specific and is activated by <protein>Ets proteins</protein> ."}
{"id": "3586", "text": "We analyzed the 5 ' transcription control sequences of the human CD4 gene .", "annotated_text": "We analyzed the <dna>5 ' transcription control sequences</dna> of the <dna>human CD4 gene</dna> ."}
{"id": "3587", "text": "We located the transcription initiation site and showed that the CD4 core promoter ( positions -40 to +16 ) lacks a classical `` TATA '' or initiator positioning consensus sequence but directs precise and efficient transcription when coupled to the ubiquitously active simian virus 40 enhancer .", "annotated_text": "We located the <dna>transcription initiation site</dna> and showed that the <dna>CD4 core promoter</dna> ( <dna>positions -40 to +16</dna> ) lacks a classical `` TATA '' or <dna>initiator positioning consensus sequence</dna> but directs precise and efficient transcription when coupled to the ubiquitously active <dna>simian virus 40 enhancer</dna> ."}
{"id": "3588", "text": "The transcriptional activity of the CD4 gene promoter correlated with CD4 expression in various cell types .", "annotated_text": "The transcriptional activity of the <dna>CD4 gene promoter</dna> correlated with CD4 expression in various cell types ."}
{"id": "3589", "text": "Interestingly , the CD4 core promoter also displayed a tissue-specific transcriptional activity .", "annotated_text": "Interestingly , the <dna>CD4 core promoter</dna> also displayed a tissue-specific transcriptional activity ."}
{"id": "3590", "text": "Within this fragment , three nucleic acid sequences are completely conserved in the murine CD4 gene .", "annotated_text": "Within this fragment , three nucleic acid sequences are completely conserved in the <dna>murine CD4 gene</dna> ."}
{"id": "3591", "text": "One of these sequences contains a perfect ETS consensus sequence .", "annotated_text": "One of these sequences contains a <dna>perfect ETS consensus sequence</dna> ."}
{"id": "3592", "text": "Another ETS consensus sequence is located 1060 nt upstream .", "annotated_text": "Another <dna>ETS consensus sequence</dna> is located 1060 nt upstream ."}
{"id": "3593", "text": "Electrophoretic-mobility-shift assays showed that the core promoter ETS motif binds an Ets-related protein specifically expressed at high levels in CD4+ cells .", "annotated_text": "Electrophoretic-mobility-shift assays showed that the core promoter ETS motif binds an <protein>Ets-related protein</protein> specifically expressed at high levels in <cell_type>CD4+ cells</cell_type> ."}
{"id": "3594", "text": "Moreover , in CD4- cells , overexpression of Ets-1 or Ets-2 efficiently and specifically activated transcription from the CD4 promoter and core promoter .", "annotated_text": "Moreover , in <cell_type>CD4- cells</cell_type> , overexpression of <protein>Ets-1</protein> or <protein>Ets-2</protein> efficiently and specifically activated transcription from the <dna>CD4 promoter</dna> and <dna>core promoter</dna> ."}
{"id": "3595", "text": "These data indicate that Ets transcription factors play a central role in controlling CD4 gene expression , by binding to both a classical remote site and an unusual proximal activator sequence", "annotated_text": "These data indicate that <protein>Ets transcription factors</protein> play a central role in controlling CD4 gene expression , by binding to both a <dna>classical remote site</dna> and an unusual <dna>proximal activator sequence</dna>"}
{"id": "3596", "text": "Glucocorticoid receptor activation and inactivation in c ultured human lymphocytes .", "annotated_text": "Glucocorticoid receptor activation and inactivation in c <cell_line>ultured human lymphocytes</cell_line> ."}
{"id": "3597", "text": "Although glucocorticoids are not cytolytic for and do not inhibit the growth of the IM-9 line of cultured human lymphoblasts , these cells have a high steroid-binding capacity .", "annotated_text": "Although glucocorticoids are not cytolytic for and do not inhibit the growth of the <cell_line>IM-9 line</cell_line> of <cell_line>cultured human lymphoblasts</cell_line> , these cells have a high steroid-binding capacity ."}
{"id": "3598", "text": "We have used IM-9 cells in order to examine whether unoccupied glucocorticoid receptors are inactivated and activated in intact cells .", "annotated_text": "We have used <cell_type>IM-9 cells</cell_type> in order to examine whether <protein>unoccupied glucocorticoid receptors</protein> are inactivated and activated in <cell_type>intact cells</cell_type> ."}
{"id": "3599", "text": "when IM-9 cells are incubated in glucose-free medium in a nitrogen atmosphere , both their ability to bind triamcinolone acetonide and their ATP levels decline and , when glucose and oxygen are reintroduced , ATP levels and receptor activity return .", "annotated_text": "when <cell_type>IM-9 cells</cell_type> are incubated in glucose-free medium in a nitrogen atmosphere , both their ability to bind triamcinolone acetonide and their ATP levels decline and , when glucose and oxygen are reintroduced , ATP levels and receptor activity return ."}
{"id": "3600", "text": "The specific glucocorticoid-binding activity of cytosol prepared from cells exposed to various degrees of energy limitation is directly correlated with the ATP content .", "annotated_text": "The specific glucocorticoid-binding activity of cytosol prepared from cells exposed to various degrees of energy limitation is directly correlated with the ATP content ."}
{"id": "3601", "text": "Receptor activation in intact cells is rapid and independent of protein synthesis .", "annotated_text": "Receptor activation in <cell_type>intact cells</cell_type> is rapid and independent of protein synthesis ."}
{"id": "3602", "text": "Cytosol prepared from inactivated cells can not be activated by addition of ATP .", "annotated_text": "Cytosol prepared from inactivated cells can not be activated by addition of ATP ."}
{"id": "3603", "text": "The inactivation of glucocorticoid receptors that occurs when cytosol from normal IM-9 cells is incubated at 25 degrees C is inhibited by molybdate , vanadate , fluoride , ATP , and several other nucleotides .", "annotated_text": "The inactivation of <protein>glucocorticoid receptors</protein> that occurs when cytosol from normal <cell_line>IM-9 cells</cell_line> is incubated at 25 degrees C is inhibited by molybdate , vanadate , fluoride , ATP , and several other nucleotides ."}
{"id": "3604", "text": "The experiments with intact human lymphoblasts suggest that assays of specific glucocorticoid-binding capacity do not necessarily reflect the cellular content of receptor protein .", "annotated_text": "The experiments with <cell_type>intact human lymphoblasts</cell_type> suggest that assays of specific glucocorticoid-binding capacity do not necessarily reflect the cellular content of <protein>receptor protein</protein> ."}
{"id": "3605", "text": "Glucocorticoids and lymphocytes .", "annotated_text": "Glucocorticoids and <cell_type>lymphocytes</cell_type> ."}
{"id": "3606", "text": "II .", "annotated_text": "II ."}
{"id": "3607", "text": "Cell cycle-dependent changes in glucocorticoid receptor content .", "annotated_text": "Cell cycle-dependent changes in <protein>glucocorticoid receptor</protein> content ."}
{"id": "3608", "text": "To study variations in glucocorticoid receptor levels during the cell cycle , we have separated mitogen-stimulated human peripheral lymphocytes and rat lymph node cells by unit gravity sedimentation and measured glucocorticoid binding in the resultant fractions .", "annotated_text": "To study variations in <protein>glucocorticoid receptor</protein> levels during the cell cycle , we have separated <cell_line>mitogen-stimulated human peripheral lymphocytes</cell_line> and <cell_type>rat lymph node cells</cell_type> by unit gravity sedimentation and measured glucocorticoid binding in the resultant fractions ."}
{"id": "3609", "text": "By morphologic criteria and thymidine incorporation , the fractions were separated into populations of G0 and G1 phase and S and post-S phase cells .", "annotated_text": "By morphologic criteria and thymidine incorporation , the fractions were separated into populations of <cell_type>G0 and G1 phase and S and post-S phase cells</cell_type> ."}
{"id": "3610", "text": "A 2- to 3-fold increase in glucocorticoid receptor sites per cell , for cells in the S and post-S phase over those in G0 and G1 , was observed with both nonstimulated rat lymph node cell suspensions and concanavalin A-stimulated human peripheral lymphocytes .", "annotated_text": "A 2- to 3-fold increase in glucocorticoid receptor sites per cell , for cells in the S and post-S phase over those in G0 and G1 , was observed with both <cell_type>nonstimulated rat lymph node cell suspensions</cell_type> and <cell_line>concanavalin A-stimulated human peripheral lymphocytes</cell_line> ."}
{"id": "3611", "text": "These observations together with those from other studies indicate that formation of new glucocorticoid receptors near the S phase may be a general phenomenon in proliferating cells .", "annotated_text": "These observations together with those from other studies indicate that formation of new <protein>glucocorticoid receptors</protein> near the S phase may be a general phenomenon in <cell_type>proliferating cells</cell_type> ."}
{"id": "3612", "text": "We propose that this increase in glucocorticoid receptors during the cell cycle may explain the increase in glucocorticoid receptors in mitogen-stimulated lymphocytes .", "annotated_text": "We propose that this increase in <protein>glucocorticoid receptors</protein> during the cell cycle may explain the increase in <protein>glucocorticoid receptors</protein> in <cell_type>mitogen-stimulated lymphocytes</cell_type> ."}
{"id": "3613", "text": "The leukocyte migration inhibition response to certain breast cancer-related antigens ( MCF-7 and MuMTV ) : their potential as discriminants .", "annotated_text": "The <cell_type>leukocyte</cell_type> migration inhibition response to certain <protein>breast cancer-related antigens</protein> ( <protein>MCF-7</protein> and <protein>MuMTV</protein> ) : their potential as discriminants ."}
{"id": "3614", "text": "Certain oncogenic viruses have been implicated in human breast cancer , including the murine mammary tumor virus ( MuMTV ) and the Mason-Pfizer monkey virus ( MPMV ) .", "annotated_text": "Certain oncogenic viruses have been implicated in human breast cancer , including the murine mammary tumor virus ( MuMTV ) and the Mason-Pfizer monkey virus ( MPMV ) ."}
{"id": "3615", "text": "We have used the leukocyte migration inhibition ( LMI ) response to assay the response to several potential breast cancer-related antigens , including MuMTV , MPMV , and a breast cancer cultured cell line , MCF-7 , in 96 breast cancer patients , in 32 women with benign breast disease , and in 67 normal women .", "annotated_text": "We have used the leukocyte migration inhibition ( LMI ) response to assay the response to several potential breast cancer-related antigens , including <protein>MuMTV</protein> , <protein>MPMV</protein> , and a <cell_line>breast cancer cultured cell line</cell_line> , <cell_line>MCF-7</cell_line> , in 96 breast cancer patients , in 32 women with benign breast disease , and in 67 normal women ."}
{"id": "3616", "text": "The lowest tenth percentile of control ( LMI ) responses was used as the cutoff point to designate responders .", "annotated_text": "The lowest tenth percentile of control ( LMI ) responses was used as the cutoff point to designate responders ."}
{"id": "3617", "text": "Breast cancer patients showed significant responses to MuMTV ( 49 % and to MCF-7 ( 50 % ) , but not to MPMV ( 29 % ) .", "annotated_text": "Breast cancer patients showed significant responses to <protein>MuMTV</protein> ( 49 % and to MCF-7 ( 50 % ) , but not to <protein>MPMV</protein> ( 29 % ) ."}
{"id": "3618", "text": "In a paired-antigen study using MuMTV and MCF-7 , 75 % of the breast cancer patients responded , versus 18 % of the normal women ( P less than 0.0050 ) .", "annotated_text": "In a paired-antigen study using <protein>MuMTV</protein> and <protein>MCF-7</protein> , 75 % of the breast cancer patients responded , versus 18 % of the normal women ( P less than 0.0050 ) ."}
{"id": "3619", "text": "The potential for this assay to distinguish `` normal '' from `` breast cancer '' was analyzed using a migration index derived from discriminant analysis .", "annotated_text": "The potential for this assay to distinguish `` normal '' from `` breast cancer '' was analyzed using a migration index derived from discriminant analysis ."}
{"id": "3620", "text": "The ability of the assay to discriminate `` normal '' from `` cancer '' was significant ( P less than 0.001 ) and showed a sensitivity of detecting `` cancer '' of 75 % .", "annotated_text": "The ability of the assay to discriminate `` normal '' from `` cancer '' was significant ( P less than 0.001 ) and showed a sensitivity of detecting `` cancer '' of 75 % ."}
{"id": "3621", "text": "The overall responses to MuMTV and MCF-7 were analyzed with reference to certain prognostic factors , but showed no relation to age , menstrual status , estrogen receptor status , or stage of disease .", "annotated_text": "The overall responses to <protein>MuMTV</protein> and <protein>MCF-7</protein> were analyzed with reference to certain prognostic factors , but showed no relation to age , menstrual status , estrogen receptor status , or stage of disease ."}
{"id": "3622", "text": "The above reactions suggest that a large proportion of breast cancer patients exhibit presensitization to antigenfs found in MuMTV and MCF-7 , which may be cross-reactive with antigens in the primary cancer .", "annotated_text": "The above reactions suggest that a large proportion of breast cancer patients exhibit presensitization to antigenfs found in <protein>MuMTV</protein> and <protein>MCF-7</protein> , which may be cross-reactive with antigens in the primary cancer ."}
{"id": "3623", "text": "These responses appear to be independent of major prognostic variables .", "annotated_text": "These responses appear to be independent of major prognostic variables ."}
{"id": "3624", "text": "Further refinement of this assay may yield one which is more highly discriminating for breast cancer .", "annotated_text": "Further refinement of this assay may yield one which is more highly discriminating for breast cancer ."}
{"id": "3625", "text": "Chronic lymphatic leukaemia : cellular effects of glucocorticoids in vitro .", "annotated_text": "Chronic lymphatic leukaemia : cellular effects of glucocorticoids in vitro ."}
{"id": "3626", "text": "Glucocorticoid receptor levels and steroid induced inhibition of nucleic acid precursors have been examined in lymphocytes from 27 patients at different stages of chronic lymphatic leukaemia .", "annotated_text": "<protein>Glucocorticoid receptor</protein> levels and steroid induced inhibition of nucleic acid precursors have been examined in <cell_type>lymphocytes</cell_type> from 27 patients at different stages of chronic lymphatic leukaemia ."}
{"id": "3627", "text": "No correlation can be found between the level of glucocorticoid receptors and the stage of the disease .", "annotated_text": "No correlation can be found between the level of <protein>glucocorticoid receptors</protein> and the stage of the disease ."}
{"id": "3628", "text": "On the other hand , a significant difference ( P less than 0.02 ) was found between stage O and stage III/IV patients , in terms of the in vitro effect of dexamethasone on [ 3H ] uridine incorporation .", "annotated_text": "On the other hand , a significant difference ( P less than 0.02 ) was found between stage O and stage III/IV patients , in terms of the in vitro effect of dexamethasone on [ 3H ] uridine incorporation ."}
{"id": "3629", "text": "Pyrrolidine dithiocarbamate inhibits NF-kappa B mobilization and TNF production in human monocytes .", "annotated_text": "Pyrrolidine dithiocarbamate inhibits <protein>NF-kappa B</protein> mobilization and TNF production in <cell_type>human monocytes</cell_type> ."}
{"id": "3630", "text": "The human TNF promoter contains four potential nuclear factor-kappa B ( NF-kappa B ) -binding sites , with the strongest binding seen for the -605 motif .", "annotated_text": "The <dna>human TNF promoter</dna> contains four potential <dna>nuclear factor-kappa B ( NF-kappa B ) -binding sites</dna> , with the strongest binding seen for the -605 motif ."}
{"id": "3631", "text": "Nuclear extracts from unstimulated cells of the human monocytic cell line , Mono Mac 6 , contain one specific binding protein ( complex II ) , consistent with a constitutive p50 homodimer .", "annotated_text": "Nuclear extracts from <cell_line>unstimulated cells</cell_line> of the <cell_line>human monocytic cell line</cell_line> , <cell_line>Mono Mac 6</cell_line> , contain one <protein>specific binding protein</protein> ( <protein>complex II</protein> ) , consistent with a <protein>constitutive p50 homodimer</protein> ."}
{"id": "3632", "text": "Stimulation of Mono Mac 6 cells with LPS will increase complex II and will strongly induce a second specific complex ( complex I ) , which represents the p50/65 heterodimer .", "annotated_text": "Stimulation of <cell_line>Mono Mac 6 cells</cell_line> with LPS will increase <protein>complex II</protein> and will strongly induce a second specific complex ( <protein>complex I</protein> ) , which represents the <protein>p50/65 heterodimer</protein> ."}
{"id": "3633", "text": "Treatment of Mono Mac 6 cells with pyrrolidine-dithiocarbamate ( PDTC ) at 300 microM will block the LPS-induced complex I almost completely and will reduce complex II to the constitutive level .", "annotated_text": "Treatment of <cell_type>Mono Mac 6 cells</cell_type> with pyrrolidine-dithiocarbamate ( PDTC ) at 300 microM will block the <protein>LPS-induced complex I</protein> almost completely and will reduce <protein>complex II</protein> to the constitutive level ."}
{"id": "3634", "text": "Binding activity of other nuclear factors that recognize the SP-1 and c/EBP motifs of the human TNF promoter is not affected by such treatment .", "annotated_text": "Binding activity of other <protein>nuclear factors</protein> that recognize the SP-1 and c/EBP motifs of the <dna>human TNF promoter</dna> is not affected by such treatment ."}
{"id": "3635", "text": "Northern blot analysis demonstrates that PDTC treatment will strongly reduce LPS-induced TNF transcripts .", "annotated_text": "Northern blot analysis demonstrates that PDTC treatment will strongly reduce <protein>LPS-induced TNF transcripts</protein> ."}
{"id": "3636", "text": "Secreted TNF protein as detected in the Wehi 164S/ActD bioassay and in a sandwich immunoassay was similarly reduced by PDTC .", "annotated_text": "Secreted <protein>TNF protein</protein> as detected in the Wehi 164S/ActD bioassay and in a sandwich immunoassay was similarly reduced by PDTC ."}
{"id": "3637", "text": "Kinetic analyses show that after LPS stimulation , NF-kappa B will peak at 1 h , TNF transcript prevalence at 2 h , and TNF protein at 4 h .", "annotated_text": "Kinetic analyses show that after LPS stimulation , <protein>NF-kappa B</protein> will peak at 1 h , TNF transcript prevalence at 2 h , and <protein>TNF protein</protein> at 4 h ."}
{"id": "3638", "text": "PDTC did not shift this response to LPS to a later time , but suppressed NF-kappa B mobilization , TNF transcripts , and TNF protein over the entire 8-h observation period .", "annotated_text": "PDTC did not shift this response to LPS to a later time , but suppressed NF-kappa B mobilization , <protein>TNF transcripts</protein> , and <protein>TNF protein</protein> over the entire 8-h observation period ."}
{"id": "3639", "text": "Analysis of freshly isolated , LPS-stimulated blood monocytes showed a similar blockade of NF-kappa B .", "annotated_text": "Analysis of freshly isolated , <cell_type>LPS-stimulated blood monocytes</cell_type> showed a similar blockade of <protein>NF-kappa B</protein> ."}
{"id": "3640", "text": "Furthermore , in these primary cells , induction of TNF transcripts , as determined by Northern blot analysis and by quantitative polymerase chain reaction , was prevented by PDTC as was TNF protein production .", "annotated_text": "Furthermore , in these primary cells , induction of <protein>TNF transcripts</protein> , as determined by Northern blot analysis and by quantitative polymerase chain reaction , was prevented by PDTC as was <protein>TNF protein</protein> production ."}
{"id": "3641", "text": "These data show that dithiocarbamates can profoundly affect cytokine expression and suggest that NF-kappa B is involved in LPS-induced TNF gene expression in human monocytes .", "annotated_text": "These data show that dithiocarbamates can profoundly affect cytokine expression and suggest that <protein>NF-kappa B</protein> is involved in LPS-induced TNF gene expression in <cell_type>human monocytes</cell_type> ."}
{"id": "3642", "text": "Comparing regions of the Epstein-Barr virus ZEBRA protein which function as transcriptional activating sequences in Saccharomyces cerevisiae and in B cells .", "annotated_text": "Comparing regions of the <protein>Epstein-Barr virus ZEBRA protein</protein> which function as <dna>transcriptional activating sequences</dna> in Saccharomyces cerevisiae and in <cell_type>B cells</cell_type> ."}
{"id": "3643", "text": "The ZEBRA protein activates expression of Epstein-Barr virus early-lytic-cycle genes in human B lymphocytes .", "annotated_text": "The <protein>ZEBRA protein</protein> activates expression of Epstein-Barr virus <dna>early-lytic-cycle genes</dna> in <cell_type>human B lymphocytes</cell_type> ."}
{"id": "3644", "text": "Here it is shown that ZEBRA also behaves as a sequence-specific transcriptional activator in Saccharomyces cerevisiae .", "annotated_text": "Here it is shown that <protein>ZEBRA</protein> also behaves as a <protein>sequence-specific transcriptional activator</protein> in Saccharomyces cerevisiae ."}
{"id": "3645", "text": "Deletional mutagenesis defined three regions of ZEBRA that participate in activation in S. cerevisiae .", "annotated_text": "Deletional mutagenesis defined three regions of <protein>ZEBRA</protein> that participate in activation in S. cerevisiae ."}
{"id": "3646", "text": "These regions are designated YI ( amino acids [ aa ] 1 to 25 ) , YII ( aa 51 to 102 ) , and YIII ( aa 228 to 245 ) .", "annotated_text": "These regions are designated <protein>YI</protein> ( <protein>amino acids [ aa ] 1 to 25</protein> ) , <protein>YII</protein> ( <protein>aa 51 to 102</protein> ) , and <protein>YIII</protein> ( <protein>aa 228 to 245</protein> ) ."}
{"id": "3647", "text": "Two of the three regions of the native ZEBRA protein act together to mediate activation when assayed on ZEBRA binding sites .", "annotated_text": "Two of the three regions of the native <protein>ZEBRA protein</protein> act together to mediate activation when assayed on <protein>ZEBRA binding sites</protein> ."}
{"id": "3648", "text": "However , when fused to the DNA binding domain of GAL 4 and assayed on GAL4 binding sites , regions YII and YIII were each sufficient to confer activation in S. cerevisiae .", "annotated_text": "However , when fused to the <protein>DNA binding domain</protein> of <protein>GAL</protein> 4 and assayed on <protein>GAL4 binding sites</protein> , <protein>regions YII and YIII</protein> were each sufficient to confer activation in S. cerevisiae ."}
{"id": "3649", "text": "Regions of ZEBRA which affected activation in S. cerevisiae were also required in human B lymphocytes .", "annotated_text": "Regions of <protein>ZEBRA</protein> which affected activation in S. cerevisiae were also required in <cell_type>human B lymphocytes</cell_type> ."}
{"id": "3650", "text": "The amino-terminal region of ZEBRA ( aa 1 to 98 ) was required for activation both in S. cerevisiae and in human B cells ; deletion of the carboxy-terminal 18 aa also significantly reduced activation in both cell types .", "annotated_text": "The <protein>amino-terminal region</protein> of <protein>ZEBRA</protein> ( <protein>aa 1 to 98</protein> ) was required for activation both in S. cerevisiae and in <cell_type>human B cells</cell_type> ; deletion of the <protein>carboxy-terminal 18 aa</protein> also significantly reduced activation in both cell types ."}
{"id": "3651", "text": "Thus , the behavior of ZEBRA in human B cells and S. cerevisiae suggests that the protein contains universal activation motifs that interact with conserved components of the transcription machinery .", "annotated_text": "Thus , the behavior of <protein>ZEBRA</protein> in <cell_type>human B cells</cell_type> and S. cerevisiae suggests that the protein contains <protein>universal activation motifs</protein> that interact with conserved components of the transcription machinery ."}
{"id": "3652", "text": "However , certain deletion mutants of ZEBRA containing mutations in the N-terminal region exhibited discordant behaviors in S. cerevisiae and in B cells .", "annotated_text": "However , certain <protein>deletion mutants</protein> of <protein>ZEBRA</protein> containing mutations in the <protein>N-terminal region</protein> exhibited discordant behaviors in S. cerevisiae and in B cells ."}
{"id": "3653", "text": "For example , deletion of ZEBRA aa 26 to 51 impaired activation to a great extent in B cells but had little or no effect in S. cerevisiae .", "annotated_text": "For example , deletion of <protein>ZEBRA aa 26 to 51</protein> impaired activation to a great extent in <cell_type>B cells</cell_type> but had little or no effect in S. cerevisiae ."}
{"id": "3654", "text": "The discordant mutants may reflect interactions with a variable domain of a conserved component or unique interactions with specialized components of the basal transcription apparatus in different cells .", "annotated_text": "The discordant mutants may reflect interactions with a <protein>variable domain</protein> of a conserved component or unique interactions with specialized components of the basal transcription apparatus in different cells ."}
{"id": "3655", "text": "Functional interaction of the v-Rel and c-Rel oncoproteins with the TATA-binding protein and association with transcription factor IIB .", "annotated_text": "Functional interaction of the <protein>v-Rel and c-Rel oncoproteins</protein> with the <protein>TATA-binding protein</protein> and association with <protein>transcription factor IIB</protein> ."}
{"id": "3656", "text": "Rel family proteins regulate the expression of genes linked to kappa B-binding motifs .", "annotated_text": "<protein>Rel family proteins</protein> regulate the expression of genes linked to kappa B-binding motifs ."}
{"id": "3657", "text": "Little is known , however , of the mechanism by which they enhance transcription .", "annotated_text": "Little is known , however , of the mechanism by which they enhance transcription ."}
{"id": "3658", "text": "We have investigated the ability of the v-Rel and c-Rel oncoproteins to interact with components of the basal transcription machinery .", "annotated_text": "We have investigated the ability of the <protein>v-Rel and c-Rel oncoproteins</protein> to interact with components of the basal transcription machinery ."}
{"id": "3659", "text": "Here we report that both the acidic transcription activation domain mapping to the unique C terminus of chicken c-Rel and the F9 cell-specific activation region common to both v-Rel and c-Rel interact with the TATA-binding protein ( TBP ) and transcription factor IIB ( TFIIB ) in vitro and in vivo .", "annotated_text": "Here we report that both the acidic transcription activation domain mapping to the unique <protein>C terminus</protein> of <protein>chicken c-Rel</protein> and the <protein>F9 cell-specific activation region</protein> common to both <protein>v-Rel</protein> and <protein>c-Rel</protein> interact with the <protein>TATA-binding protein</protein> ( <protein>TBP</protein> ) and <protein>transcription factor IIB</protein> ( <protein>TFIIB</protein> ) in vitro and in vivo ."}
{"id": "3660", "text": "We also demonstrate that TPB interaction with Rel activation regions leads to synergistic activation of transcription of a kappa B-linked reporter gene .", "annotated_text": "We also demonstrate that <protein>TPB</protein> interaction with <protein>Rel activation regions</protein> leads to synergistic activation of transcription of a <dna>kappa B-linked reporter gene</dna> ."}
{"id": "3661", "text": "Combined with the observation that the mouse c-Rel and human RelA proteins also interact with TBP and TFIIB in vitro , these results suggest that association with basal transcription factors is important for the transcriptional activities of Rel family proteins .", "annotated_text": "Combined with the observation that the <protein>mouse c-Rel and human RelA proteins</protein> also interact with <protein>TBP</protein> and <protein>TFIIB</protein> in vitro , these results suggest that association with <protein>basal transcription factors</protein> is important for the transcriptional activities of <protein>Rel family proteins</protein> ."}
{"id": "3662", "text": "p21ras and calcineurin synergize to regulate the nuclear factor of activated T cells .", "annotated_text": "<protein>p21ras</protein> and calcineurin synergize to regulate the <protein>nuclear factor</protein> of activated <cell_type>T cells</cell_type> ."}
{"id": "3663", "text": "In T lymphocytes , triggering of the T cell receptor ( TCR ) induces several signaling cascades which ultimately synergize to induce the activity of the nuclear factor of activated T cells ( NFAT ) , a DNA binding complex critical to the inducibility and T cell specificity of the T cell growth factor interleukin 2 .", "annotated_text": "In <cell_type>T lymphocytes</cell_type> , triggering of the <protein>T cell receptor</protein> ( <protein>TCR</protein> ) induces several signaling cascades which ultimately synergize to induce the activity of the <protein>nuclear factor</protein> of activated <cell_type>T cells</cell_type> ( <cell_line>NFAT</cell_line> ) , a <protein>DNA binding complex</protein> critical to the inducibility and T cell specificity of the <protein>T cell growth factor</protein> <protein>interleukin 2</protein> ."}
{"id": "3664", "text": "One immediate consequence of T cell activation via the TCR is an increase in cytosolic calcium .", "annotated_text": "One immediate consequence of T cell activation via the <protein>TCR</protein> is an increase in cytosolic calcium ."}
{"id": "3665", "text": "Calcium signals are important for NFAT induction , and recent studies have identified calcineurin , a calcium-calmodulin dependent serine-threonine phosphatase , as a prominent component of the calcium signaling pathway in T cells .", "annotated_text": "Calcium signals are important for <cell_line>NFAT</cell_line> induction , and recent studies have identified <protein>calcineurin</protein> , a <protein>calcium-calmodulin dependent serine-threonine phosphatase</protein> , as a prominent component of the calcium signaling pathway in <cell_type>T cells</cell_type> ."}
{"id": "3666", "text": "A second important molecule in TCR signal transduction is the guanine nucleotide binding protein , p21ras , which is coupled to the TCR by a protein tyrosine kinase dependent mechanism .", "annotated_text": "A second important molecule in TCR signal transduction is the <protein>guanine nucleotide binding protein</protein> , <protein>p21ras</protein> , which is coupled to the <protein>TCR</protein> by a <protein>protein tyrosine kinase</protein> dependent mechanism ."}
{"id": "3667", "text": "The experiments presented here show that expression by transfection of mutationally activated calcineurin or activated p21ras alone is insufficient for NFAT transactivation .", "annotated_text": "The experiments presented here show that expression by transfection of mutationally activated <protein>calcineurin</protein> or activated <protein>p21ras</protein> alone is insufficient for <cell_type>NFAT</cell_type> transactivation ."}
{"id": "3668", "text": "However , coexpression of the activated calcineurin with activated p21ras could mimic TCR signals in NFAT induction .", "annotated_text": "However , coexpression of the activated calcineurin with activated p21ras could mimic TCR signals in <cell_type>NFAT</cell_type> induction ."}
{"id": "3669", "text": "These data identify calcineurin and p21ras as cooperative partners in T cell activation .", "annotated_text": "These data identify <protein>calcineurin</protein> and <protein>p21ras</protein> as cooperative partners in <cell_type>T cell</cell_type> activation ."}
{"id": "3670", "text": "Expression of the chicken GATA factor family during early erythroid development and differentiation .", "annotated_text": "Expression of the <protein>chicken GATA factor family</protein> during early erythroid development and differentiation ."}
{"id": "3671", "text": "The DNA motif WGATAR has been identified within transcriptional regulatory domains of globin and other erythroid-specific genes and the activator proteins that bind to this regulatory element , the GATA factors , belong to a multi-gene family that is expressed in chicken erythroid cells .", "annotated_text": "The DNA motif WGATAR has been identified within <dna>transcriptional regulatory domains</dna> of <dna>globin</dna> and other <dna>erythroid-specific genes</dna> and the <protein>activator proteins</protein> that bind to this <dna>regulatory element</dna> , the <protein>GATA factors</protein> , belong to a <protein>multi-gene family</protein> that is expressed in <cell_type>chicken erythroid cells</cell_type> ."}
{"id": "3672", "text": "Here we show that , as in chickens , multiple members of the GATA factor family are expressed in human and murine erythroid cells .", "annotated_text": "Here we show that , as in chickens , multiple members of the <protein>GATA factor family</protein> are expressed in <cell_type>human and murine erythroid cells</cell_type> ."}
{"id": "3673", "text": "During the early stages of chicken embryogenesis ( well before blood island formation ) , each of the GATA family members is transcribed with a unique temporal and spatial pattern .", "annotated_text": "During the early stages of chicken embryogenesis ( well before blood island formation ) , each of the <protein>GATA family members</protein> is transcribed with a unique temporal and spatial pattern ."}
{"id": "3674", "text": "In the primitive erythroid lineage , transcription of the embryonic epsilon-globin gene parallels GATA-1 expression while the switch to beta-globin transcription in definitive erythroid cells is directly preceded by a pronounced increase in GATA-3 accumulation .", "annotated_text": "In the <cell_type>primitive erythroid lineage</cell_type> , transcription of the <dna>embryonic epsilon-globin gene</dna> parallels GATA-1 expression while the switch to beta-globin transcription in <cell_type>definitive erythroid cells</cell_type> is directly preceded by a pronounced increase in <protein>GATA-3</protein> accumulation ."}
{"id": "3675", "text": "The timing and pattern of expression of these different mRNAs during avian erythroid development and differentiation suggests that temporally regulated changes in GATA factor expression are required for vertebrate hematopoiesis .", "annotated_text": "The timing and pattern of expression of these different <rna>mRNAs</rna> during avian erythroid development and differentiation suggests that temporally regulated changes in <protein>GATA factor</protein> expression are required for vertebrate hematopoiesis ."}
{"id": "3676", "text": "Molecular regulation of human interleukin 2 and T-cell function by interleukin 4 .", "annotated_text": "Molecular regulation of <protein>human interleukin 2</protein> and <cell_type>T-cell</cell_type> function by <protein>interleukin 4</protein> ."}
{"id": "3677", "text": "Distinct functional T-cell subsets , differing in the patterns of lymphokines produced , regulate cell-mediated and humoral immune responses .", "annotated_text": "Distinct functional <cell_type>T-cell subsets</cell_type> , differing in the patterns of <protein>lymphokines</protein> produced , regulate cell-mediated and humoral immune responses ."}
{"id": "3678", "text": "The two major types and their principal products , interleukin 4 and interferon gamma ( IL-4 and IFN-gamma ) , are reciprocally negatively interactive .", "annotated_text": "The two major types and their principal products , <protein>interleukin 4</protein> and <protein>interferon gamma</protein> ( <protein>IL-4</protein> and <protein>IFN-gamma</protein> ) , are reciprocally negatively interactive ."}
{"id": "3679", "text": "To analyze the molecular mechanism of IL-4-mediated suppression of cell-mediated immunity we studied its effects on expression of interleukin 2 ( IL-2 ) and IFN-gamma .", "annotated_text": "To analyze the molecular mechanism of IL-4-mediated suppression of cell-mediated immunity we studied its effects on expression of <protein>interleukin 2</protein> ( <protein>IL-2</protein> ) and <protein>IFN-gamma</protein> ."}
{"id": "3680", "text": "IL-4 pretreatment of Jurkat cells prior to stimulation resulted in a decrease in transcription of the IL2 gene .", "annotated_text": "<protein>IL-4</protein> pretreatment of <cell_type>Jurkat cells</cell_type> prior to stimulation resulted in a decrease in transcription of the <dna>IL2 gene</dna> ."}
{"id": "3681", "text": "IL-4 suppressed IL-2 and IFN-gamma mRNA levels in primary human T cells , and addition of anti-CD28 antibodies relieved this suppression .", "annotated_text": "<protein>IL-4</protein> suppressed IL-2 and IFN-gamma mRNA levels in <cell_type>primary human T cells</cell_type> , and addition of <protein>anti-CD28 antibodies</protein> relieved this suppression ."}
{"id": "3682", "text": "Using enhancer-reporter constructs , IL-4 specifically down-regulated the NFIL-2B element .", "annotated_text": "Using <dna>enhancer-reporter constructs</dna> , <protein>IL-4</protein> specifically down-regulated the <dna>NFIL-2B element</dna> ."}
{"id": "3683", "text": "Electrophoretic mobility shift assays using a DNA oligomer containing the NFIL-2B binding site indicated that IL-4 inhibited the NFIL-2B complex and that the NFIL-2B DNA binding factor is distinct from AP- 1 .", "annotated_text": "Electrophoretic mobility shift assays using a DNA oligomer containing the <dna>NFIL-2B binding site</dna> indicated that <protein>IL-4</protein> inhibited the <protein>NFIL-2B complex</protein> and that the <protein>NFIL-2B DNA binding factor</protein> is distinct from <protein>AP-</protein> 1 ."}
{"id": "3684", "text": "These results suggest that IL-4 may regulate development and function of T-cell subsets involved in cell-mediated immunity in part by inhibiting factors required for transcription of the IL2 gene", "annotated_text": "These results suggest that <protein>IL-4</protein> may regulate development and function of <cell_type>T-cell subsets</cell_type> involved in cell-mediated immunity in part by <protein>inhibiting factors</protein> required for transcription of the <dna>IL2 gene</dna>"}
{"id": "3685", "text": "Immunochemical differences between glucocorticoid receptors from corticoid-sensitive and -resistant malignant lymphocytes .", "annotated_text": "Immunochemical differences between <protein>glucocorticoid receptors</protein> from <cell_type>corticoid-sensitive and -resistant malignant lymphocytes</cell_type> ."}
{"id": "3686", "text": "We have explored the possibility of using antibodies against purified rat liver glucocorticoid receptors to study the immunochemical properties of glucocorticoid receptors from murine and human malignant lymphocytes .", "annotated_text": "We have explored the possibility of using <protein>antibodies</protein> against purified rat liver <protein>glucocorticoid receptors</protein> to study the immunochemical properties of <protein>glucocorticoid receptors</protein> from <cell_type>murine and human malignant lymphocytes</cell_type> ."}
{"id": "3687", "text": "For this purpose , purified immune immunoglobulin G was covalently linked to Sepharose CL-4B .", "annotated_text": "For this purpose , <protein>purified immune immunoglobulin G</protein> was covalently linked to <protein>Sepharose CL-4B</protein> ."}
{"id": "3688", "text": "We then examined the ability of the affinity gel to recognize cytosolic [ 3H ] triamcinolone acetonide-receptor complexes from the corticoid-sensitive ( CS ) and -resistant strains of mouse lymphoma P1798 , from CS lymphocytes of patients with chronic lymphatic leukemia , and from a CS clone of human leukemic lymphoblasts in tissue culture ( CH6 ) .", "annotated_text": "We then examined the ability of the affinity gel to recognize <protein>cytosolic [ 3H ] triamcinolone acetonide-receptor complexes</protein> from the <cell_line>corticoid-sensitive ( CS ) and -resistant strains of mouse lymphoma P1798</cell_line> , from <cell_type>CS lymphocytes</cell_type> of patients with chronic lymphatic leukemia , and from a <cell_line>CS clone</cell_line> of <cell_type>human leukemic lymphoblasts</cell_type> in tissue culture ( <cell_line>CH6</cell_line> ) ."}
{"id": "3689", "text": "Mouse thymus was used as a source of glucocorticoid receptor from normal CS lymphocytes .", "annotated_text": "Mouse thymus was used as a source of <protein>glucocorticoid receptor</protein> from <cell_type>normal CS lymphocytes</cell_type> ."}
{"id": "3690", "text": "Whereas the immunoaffinity column retained 70 to 84 % of the 58- to 62-A ( Stokes radius ) [ 3H ] triamcinolone acetonide-receptor complexes characteristic of the CS mouse and human lymphocytes , it failed to recognize the 27- to 28-A ( Stokes radius ) glucocorticoid receptor present in corticoid-resistant mouse lymphoma P1798 cells .", "annotated_text": "Whereas the immunoaffinity column retained 70 to 84 % of the 58- to 62-A ( Stokes radius ) <protein>[ 3H ] triamcinolone acetonide-receptor complexes</protein> characteristic of the <cell_line>CS mouse and human lymphocytes</cell_line> , it failed to recognize the 27- to 28-A ( Stokes radius ) <protein>glucocorticoid receptor</protein> present in corticoid-resistant <cell_line>mouse lymphoma P1798 cells</cell_line> ."}
{"id": "3691", "text": "Therefore , under appropriate experimental conditions , it was possible to demonstrate cross-reactivity between the antiserum against rat liver glucocorticoid receptor and the 58- to 62-A ( Stokes radius ) glucocorticoid receptor from species as diverse as mouse and humans .", "annotated_text": "Therefore , under appropriate experimental conditions , it was possible to demonstrate cross-reactivity between the antiserum against <protein>rat liver glucocorticoid receptor</protein> and the 58- to 62-A ( Stokes radius ) <protein>glucocorticoid receptor</protein> from species as diverse as mouse and humans ."}
{"id": "3692", "text": "Heterogeneity of the in vitro responses to glucocorticoids in acute leukemia .", "annotated_text": "Heterogeneity of the in vitro responses to glucocorticoids in acute leukemia ."}
{"id": "3693", "text": "In leukocyte population freshly isolated from the blood of 26 patients with acute leukemia , we have measured several parameters including glucocorticoid receptors , nucleoside incorporation , percentage of cells in S phase , and steroid-induced cell lysis .", "annotated_text": "In <cell_type>leukocyte population</cell_type> freshly isolated from the blood of 26 patients with acute leukemia , we have measured several parameters including <protein>glucocorticoid receptors</protein> , nucleoside incorporation , percentage of cells in S phase , and steroid-induced cell lysis ."}
{"id": "3694", "text": "In addition , in some cases , the short-term response to steroid therapy was determined .", "annotated_text": "In addition , in some cases , the short-term response to steroid therapy was determined ."}
{"id": "3695", "text": "Although , in all the patients studied , leukocytes were found to contain glucocorticoid receptors , we failed to demonstrate any correlation between the level of binding sites and the in vitro or in vivo response to glucocorticoids .", "annotated_text": "Although , in all the patients studied , <cell_type>leukocytes</cell_type> were found to contain <protein>glucocorticoid receptors</protein> , we failed to demonstrate any correlation between the level of binding sites and the in vitro or in vivo response to glucocorticoids ."}
{"id": "3696", "text": "This absence of correlation could be in part explained by the marked heterogeneity of the steroid response demonstrated in leukocyte subpopulations .", "annotated_text": "This absence of correlation could be in part explained by the marked heterogeneity of the steroid response demonstrated in leukocyte subpopulations ."}
{"id": "3697", "text": "It appears , however , that the degree of steroid action in vitro as well as the extent of spontaneous and dexamethasone-induced cell death may be related to the number of cells in the S phase of the cell cycle .", "annotated_text": "It appears , however , that the degree of steroid action in vitro as well as the extent of spontaneous and dexamethasone-induced cell death may be related to the number of cells in the S phase of the cell cycle ."}
{"id": "3698", "text": "Glucocorticoid receptors in cytosol and nuclear extract of human leukocytes .", "annotated_text": "<protein>Glucocorticoid receptors</protein> in cytosol and nuclear extract of <cell_type>human leukocytes</cell_type> ."}
{"id": "3699", "text": "Cortisol binding by cytosol and 0.4 M KCl extract of the nuclear fraction of human leukocytes were studied by gel chromatography and ion exchange filtration on DEAE cellulose .", "annotated_text": "Cortisol binding by cytosol and 0.4 M KCl extract of the nuclear fraction of <cell_type>human leukocytes</cell_type> were studied by gel chromatography and ion exchange filtration on DEAE cellulose ."}
{"id": "3700", "text": "The cytoplasmic cortisol binding protein has a molecular weight 95 000 and the soluble nuclear binding protein 50 000 .", "annotated_text": "The <protein>cytoplasmic cortisol binding protein</protein> has a molecular weight 95 000 and the <protein>soluble nuclear binding protein</protein> 50 000 ."}
{"id": "3701", "text": "The absence of the uptake of radioactive cortisol by isolated nuclei and the apparent requirement of the cytosol for glucocorticoid specific binding in nuclear receptor sites was observed .", "annotated_text": "The absence of the uptake of radioactive cortisol by isolated nuclei and the apparent requirement of the cytosol for glucocorticoid specific binding in nuclear receptor sites was observed ."}
{"id": "3702", "text": "The association constant characterising the binding of cortisol to cytosol was KA = 3.5 . 10 ( 9 ) l/mol .", "annotated_text": "The association constant characterising the binding of cortisol to cytosol was KA = 3.5 . 10 ( 9 ) l/mol ."}
{"id": "3703", "text": "Corticosteroid-induced lymphopenia , immunosuppression , and body defense .", "annotated_text": "Corticosteroid-induced lymphopenia , immunosuppression , and body defense ."}
{"id": "3704", "text": "The apparent paradox of heightened adrenal corticosteroid levels associated with reduction in the competence of the body 's defensive apparatus to cope with exposure to new microbial antigens is considered .", "annotated_text": "The apparent paradox of heightened adrenal corticosteroid levels associated with reduction in the competence of the body 's defensive apparatus to cope with exposure to new <protein>microbial antigens</protein> is considered ."}
{"id": "3705", "text": "The question is asked how this lowered defensive capability , which occurs in the face of a threat to body integrity , is consistent with Cannon 's principals of the `` wisdom of the body. ''", "annotated_text": "The question is asked how this lowered defensive capability , which occurs in the face of a threat to body integrity , is consistent with Cannon 's principals of the `` wisdom of the body. ''"}
{"id": "3706", "text": "The suggestion is offered that the immunologic response to self-antigens exposed by disease or trauma may be suppressed by corticosteroid to offset the likelihood of autoimmune attack .", "annotated_text": "The suggestion is offered that the immunologic response to <protein>self-antigens</protein> exposed by disease or trauma may be suppressed by corticosteroid to offset the likelihood of autoimmune attack ."}
{"id": "3707", "text": "Protein tyrosine kinase activation is required for lipopolysaccharide induction of cytokines in human blood monocytes .", "annotated_text": "<protein>Protein tyrosine kinase</protein> activation is required for lipopolysaccharide induction of <protein>cytokines</protein> in <cell_type>human blood monocytes</cell_type> ."}
{"id": "3708", "text": "Bacterial LPS induce production of cytokines such as IL-1 , IL-6 , and TNF in mononuclear phagocytes , and this represents a central component in the pathogenesis of septic shock syndrome .", "annotated_text": "Bacterial LPS induce production of <protein>cytokines</protein> such as <protein>IL-1</protein> , <protein>IL-6</protein> , and <protein>TNF</protein> in <cell_type>mononuclear phagocytes</cell_type> , and this represents a central component in the pathogenesis of septic shock syndrome ."}
{"id": "3709", "text": "However , the mechanisms by which LPS activates these cells to express cytokines are not completely characterized .", "annotated_text": "However , the mechanisms by which LPS activates these cells to express <protein>cytokines</protein> are not completely characterized ."}
{"id": "3710", "text": "The present study addressed the role of different protein kinases in the LPS induction of cytokines .", "annotated_text": "The present study addressed the role of different <protein>protein kinases</protein> in the LPS induction of <protein>cytokines</protein> ."}
{"id": "3711", "text": "It is shown that LPS induced a 12- to 16-fold increase in IL-1 beta , IL-6 , and TNF-alpha mRNA levels , and this was completely or more than 80 % blocked by the protein tyrosine kinase specific inhibitors herbimycin A and genistein at the concentrations of 1.7 and 37 microM , respectively .", "annotated_text": "It is shown that LPS induced a 12- to 16-fold increase in IL-1 beta , IL-6 , and TNF-alpha mRNA levels , and this was completely or more than 80 % blocked by the protein tyrosine kinase specific inhibitors herbimycin A and genistein at the concentrations of 1.7 and 37 microM , respectively ."}
{"id": "3712", "text": "Protein kinase C inhibition by staurosporine reduced LPS induction of TNF-alpha , whereas it had no effects on IL-6 and IL-1 beta .", "annotated_text": "<protein>Protein kinase C</protein> inhibition by staurosporine reduced LPS induction of <protein>TNF-alpha</protein> , whereas it had no effects on <protein>IL-6</protein> and IL-1 beta ."}
{"id": "3713", "text": "Inhibition of protein kinase A by H89 reduced IL-6 mRNA levels but did not detectably change IL-1 beta or TNF-alpha mRNA levels .", "annotated_text": "Inhibition of <protein>protein kinase A</protein> by H89 reduced <rna>IL-6 mRNA</rna> levels but did not detectably change IL-1 beta or TNF-alpha mRNA levels ."}
{"id": "3714", "text": "In contrast , LPS did not increase leukemia inhibitory factor mRNA , which was constitutively expressed and not significantly reduced by these inhibitors .", "annotated_text": "In contrast , LPS did not increase <rna>leukemia inhibitory factor mRNA</rna> , which was constitutively expressed and not significantly reduced by these inhibitors ."}
{"id": "3715", "text": "In addition to cytokine mRNA levels , LPS-induced IL-6 protein synthesis and IL-6 bioactivity were also reduced to baseline levels by the PTK inhibitors herbimycin A and genistein .", "annotated_text": "In addition to <rna>cytokine mRNA</rna> levels , LPS-induced IL-6 protein synthesis and IL-6 bioactivity were also reduced to baseline levels by the PTK inhibitors herbimycin A and genistein ."}
{"id": "3716", "text": "Both PTK inhibitors also reduced the LPS activation of nuclear factor-kappa B ( NF-kappa B ) , which is a transcription factor involved in the expression of cytokine genes such as IL-6 and TNF-alpha .", "annotated_text": "Both PTK inhibitors also reduced the LPS activation of <protein>nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) , which is a <protein>transcription factor</protein> involved in the expression of <rna>cytokine genes</rna> such as <dna>IL-6</dna> and <dna>TNF-alpha</dna> ."}
{"id": "3717", "text": "The activation of NF-kappa B was also reduced by H89 , whereas staurosporine had no effect on this response .", "annotated_text": "The activation of <protein>NF-kappa B</protein> was also reduced by H89 , whereas staurosporine had no effect on this response ."}
{"id": "3718", "text": "In summary , these findings suggest that protein kinase C and protein kinase A appear to have selective effects in the LPS induction of cytokines , whereas PTK is required for LPS induction of a broad spectrum of cytokines and NF-kappa B activation in monocytes .", "annotated_text": "In summary , these findings suggest that <protein>protein kinase C</protein> and <protein>protein kinase A</protein> appear to have selective effects in the LPS induction of <protein>cytokines</protein> , whereas <protein>PTK</protein> is required for LPS induction of a broad spectrum of <protein>cytokines</protein> and <protein>NF-kappa B</protein> activation in <cell_type>monocytes</cell_type> ."}
{"id": "3719", "text": "In vivo control of NF-kappa B activation by I kappa B alpha .", "annotated_text": "In vivo control of <protein>NF-kappa B</protein> activation by <protein>I kappa B alpha</protein> ."}
{"id": "3720", "text": "The transcription factor NF-kappa B is stored in the cytoplasm in complexes with the inhibitor protein I kappa B alpha .", "annotated_text": "The <protein>transcription factor</protein> <protein>NF-kappa B</protein> is stored in the cytoplasm in complexes with the <protein>inhibitor protein I kappa B alpha</protein> ."}
{"id": "3721", "text": "It has been shown in vitro that dissociation of I kappa B alpha from these complexes results in active NF-kappa B .", "annotated_text": "It has been shown in vitro that dissociation of <protein>I kappa B alpha</protein> from these complexes results in <protein>active NF-kappa B</protein> ."}
{"id": "3722", "text": "In this report we show that lipopolysaccharide ( LPS ) -induced activation of B or pre-B cells results in loss of I kappa B alpha from NF-kappa B complexes in vivo .", "annotated_text": "In this report we show that lipopolysaccharide ( LPS ) -induced activation of <cell_type>B or pre-B cells</cell_type> results in loss of <protein>I kappa B alpha</protein> from <protein>NF-kappa B complexes</protein> in vivo ."}
{"id": "3723", "text": "Many liberated NF-kappa B dimers reached the nucleus , where increased c-rel , p65 and p50 were detected by immunoblotting and by DNA binding assays .", "annotated_text": "Many liberated <protein>NF-kappa B dimers</protein> reached the nucleus , where increased <protein>c-rel</protein> , p65 and p50 were detected by immunoblotting and by DNA binding assays ."}
{"id": "3724", "text": "Some liberated dimers were retained in the cytoplasm , however , through binding to newly synthesized I kappa B alpha , a finding which strongly suggests ( i ) that the LPS-induced signal causes dissociation of complexes rather than preventing their association and ( ii ) that dissociation results from modification of I kappa B alpha and not of c-rel or p65 .", "annotated_text": "Some <protein>liberated dimers</protein> were retained in the cytoplasm , however , through binding to newly synthesized <protein>I kappa B alpha</protein> , a finding which strongly suggests ( i ) that the LPS-induced signal causes dissociation of complexes rather than preventing their association and ( ii ) that dissociation results from modification of <protein>I kappa B alpha</protein> and not of <protein>c-rel</protein> or <protein>p65</protein> ."}
{"id": "3725", "text": "No effect of LPS treatment was detected on p105 or p100 , which also retain rel family members in the cytoplasm .", "annotated_text": "No effect of LPS treatment was detected on <protein>p105</protein> or <protein>p100</protein> , which also retain <protein>rel family members</protein> in the cytoplasm ."}
{"id": "3726", "text": "Quite unexpectedly , we also found that in unstimulated cells there is a constant ongoing process of degradation and replacement of complexed I kappa B alpha .", "annotated_text": "Quite unexpectedly , we also found that in <cell_type>unstimulated cells</cell_type> there is a constant ongoing process of degradation and replacement of <protein>complexed I kappa B alpha</protein> ."}
{"id": "3727", "text": "We propose that this turnover results in the low level of active NF-kappa B presumably necessary even in the unstimulated cell , and that the high rate of synthesis of I kappa B alpha provides the ability to turn off NF-kappa B activity rapidly as soon as the activating signal ceases .", "annotated_text": "We propose that this turnover results in the low level of <protein>active NF-kappa B</protein> presumably necessary even in the unstimulated cell , and that the high rate of synthesis of <protein>I kappa B alpha</protein> provides the ability to turn off <protein>NF-kappa B</protein> activity rapidly as soon as the activating signal ceases ."}
{"id": "3728", "text": "Identification of a killer cell-specific regulatory element of the mouse perforin gene : an Ets-binding site-homologous motif that interacts with Ets-related proteins .", "annotated_text": "Identification of a <dna>killer cell-specific regulatory element</dna> of the <dna>mouse perforin gene</dna> : an Ets-binding site-homologous motif that interacts with <protein>Ets-related proteins</protein> ."}
{"id": "3729", "text": "The gene encoding the cytolytic protein perforin is selectively expressed by activated killer lymphocytes .", "annotated_text": "The gene encoding the <protein>cytolytic protein</protein> <protein>perforin</protein> is selectively expressed by <cell_type>activated killer lymphocytes</cell_type> ."}
{"id": "3730", "text": "To understand the mechanisms underlying the cell-type-specific expression of this gene , we have characterized the regulatory functions and the DNA-protein interactions of the 5'-flanking region of the mouse perforin gene ( Pfp ) .", "annotated_text": "To understand the mechanisms underlying the cell-type-specific expression of this gene , we have characterized the regulatory functions and the DNA-protein interactions of the <dna>5'-flanking region</dna> of the <dna>mouse perforin gene</dna> ( <dna>Pfp</dna> ) ."}
{"id": "3731", "text": "A region extending from residues +62 through -141 , which possesses the essential promoter activity , and regions further upstream , which are able to either enhance or suppress gene expression , were identified .", "annotated_text": "A region extending from <dna>residues +62 through -141</dna> , which possesses the essential promoter activity , and regions further upstream , which are able to either enhance or suppress gene expression , were identified ."}
{"id": "3732", "text": "The region between residues -411 and -566 was chosen for further characterization , since it contains an enhancer-like activity .", "annotated_text": "The region between <dna>residues -411 and -566</dna> was chosen for further characterization , since it contains an enhancer-like activity ."}
{"id": "3733", "text": "We have identified a 32-mer sequence ( residues -491 to -522 ) which appeared to be capable of enhancing gene expression in a killer cell-specific manner .", "annotated_text": "We have identified a 32-mer sequence ( <dna>residues -491 to -522</dna> ) which appeared to be capable of enhancing gene expression in a killer cell-specific manner ."}
{"id": "3734", "text": "Within this segment , a 9-mer motif ( 5'-ACAGGAAGT-3 ' , residues -505 to -497 ; designated NF-P motif ) , which is highly homologous to the Ets proto-oncoprotein-binding site , was found to interact with two proteins , NF-P1 and NF-P2 .", "annotated_text": "Within this segment , a 9-mer motif ( 5'-ACAGGAAGT-3 ' , <dna>residues -505 to -497</dna> ; designated NF-P motif ) , which is highly homologous to the <dna>Ets proto-oncoprotein-binding site</dna> , was found to interact with two proteins , <protein>NF-P1</protein> and <protein>NF-P2</protein> ."}
{"id": "3735", "text": "NF-P2 appears to be induced by reagents known to up-regulate the perforin message level and is present exclusively in killer cells .", "annotated_text": "<protein>NF-P2</protein> appears to be induced by reagents known to up-regulate the perforin message level and is present exclusively in <cell_type>killer cells</cell_type> ."}
{"id": "3736", "text": "Electrophoretic mobility shift assay and UV cross-linking experiments revealed that NF-P1 and NF-P2 may possess common DNA-binding subunits .", "annotated_text": "Electrophoretic mobility shift assay and UV cross-linking experiments revealed that <protein>NF-P1</protein> and <protein>NF-P2</protein> may possess common <protein>DNA-binding subunits</protein> ."}
{"id": "3737", "text": "However , the larger native molecular mass of NF-P1 suggests that NF-P1 contains an additional non-DNA-binding subunit ( s ) .", "annotated_text": "However , the larger native molecular mass of <protein>NF-P1</protein> suggests that <protein>NF-P1</protein> contains an additional <protein>non-DNA-binding subunit</protein> ( s ) ."}
{"id": "3738", "text": "In view of the homology between the NF-P motif and other Ets proto-oncoprotein-binding sites , it is postulated that NF-P1 and NF-P2 belong to the Ets protein family .", "annotated_text": "In view of the homology between the <protein>NF-P motif</protein> and other <protein>Ets proto-oncoprotein-binding sites</protein> , it is postulated that <protein>NF-P1</protein> and <protein>NF-P2</protein> belong to the <protein>Ets protein family</protein> ."}
{"id": "3739", "text": "Results obtained from the binding competition assay , nevertheless , suggest that NF-P1 and NF-P2 are related to but distinct from Ets proteins , e.g. , Ets-1 , Ets-2 , and NF-AT/Elf-1 , known to be expressed in T cells .", "annotated_text": "Results obtained from the binding competition assay , nevertheless , suggest that <protein>NF-P1</protein> and <protein>NF-P2</protein> are related to but distinct from <protein>Ets proteins</protein> , e.g. , <protein>Ets-1</protein> , <protein>Ets-2</protein> , and <protein>NF-AT/Elf-1</protein> , known to be expressed in <cell_type>T cells</cell_type> ."}
{"id": "3740", "text": "The role of NF-kappa B1 ( p50/p105 ) gene expression in activation of human blood T-lymphocytes via CD2 and CD28 adhesion molecules .", "annotated_text": "The role of <dna>NF-kappa B1 ( p50/p105 ) gene</dna> expression in activation of <cell_type>human blood T-lymphocytes</cell_type> via <protein>CD2 and CD28 adhesion molecules</protein> ."}
{"id": "3741", "text": "Stimulation of primary human T-lymphocytes via CD2 and CD28 adhesion molecules induces a long-lasting proliferation ( > 3 weeks ) .", "annotated_text": "Stimulation of <cell_type>primary human T-lymphocytes</cell_type> via <protein>CD2 and CD28 adhesion molecules</protein> induces a long-lasting proliferation ( > 3 weeks ) ."}
{"id": "3742", "text": "This potent activation does not require accessory cells , such as monocytes , but depends on persistent interleukin 2 ( IL-2 ) secretion and receptivity , which is associated with high and prolonged expression of the inducible CD25/IL-2 receptor alpha ( IL-2R alpha ) chain gene .", "annotated_text": "This potent activation does not require accessory cells , such as <cell_type>monocytes</cell_type> , but depends on persistent <protein>interleukin 2</protein> ( <protein>IL-2</protein> ) secretion and receptivity , which is associated with high and prolonged expression of the inducible <dna>CD25/IL-2 receptor alpha ( IL-2R alpha ) chain gene</dna> ."}
{"id": "3743", "text": "The transcription factor NF-kappa B participates in the regulation of both IL-2 and IL-2R alpha genes , as well as multiple cellular genes involved in T-cell proliferation .", "annotated_text": "The <protein>transcription factor NF-kappa B</protein> participates in the regulation of both <dna>IL-2 and IL-2R alpha genes</dna> , as well as <dna>multiple cellular genes</dna> involved in T-cell proliferation ."}
{"id": "3744", "text": "To evaluate the role of NF-kappa B in human peripheral blood T-lymphocytes , we previously analyzed the activation of NF-kappa B-related complexes in response to CD2+CD28 costimulation .", "annotated_text": "To evaluate the role of <protein>NF-kappa B</protein> in <cell_type>human peripheral blood T-lymphocytes</cell_type> , we previously analyzed the activation of <protein>NF-kappa B-related complexes</protein> in response to CD2+CD28 costimulation ."}
{"id": "3745", "text": "We demonstrated a long-term induction of p50/p65 heterodimer , a putative p65/c-Rel heterodimer , and a constitutive nuclear expression of KBF1/p50 homodimers .", "annotated_text": "We demonstrated a long-term induction of <protein>p50/p65 heterodimer</protein> , a <protein>putative p65/c-Rel heterodimer</protein> , and a constitutive nuclear expression of <protein>KBF1/p50 homodimers .</protein>"}
{"id": "3746", "text": "As the role of p50 remains unclear , we focused our present study on NF-kappa B1 ( p50/p105 ) gene regulation .", "annotated_text": "As the role of <protein>p50</protein> remains unclear , we focused our present study on <protein>NF-kappa B1</protein> ( <protein>p50/p105</protein> ) gene regulation ."}
{"id": "3747", "text": "Using electrophoretic mobility shift assays and Western and Northern blot analyses , we studied NF-kappa B1 gene expression during T-cell stimulation via CD2+CD28 .", "annotated_text": "Using electrophoretic mobility shift assays and Western and Northern blot analyses , we studied <dna>NF-kappa B1 gene</dna> expression during T-cell stimulation via <protein>CD2+CD28</protein> ."}
{"id": "3748", "text": "We observed a transient 4- to 5-fold increase of NF-kappa B1 gene expression at both the mRNA and protein levels , lasting for at least 24 h .", "annotated_text": "We observed a transient 4- to 5-fold increase of NF-kappa B1 gene expression at both the mRNA and protein levels , lasting for at least 24 h ."}
{"id": "3749", "text": "p50 DNA-binding activity apparently stays highly controlled when p105 expression is enhanced by a physiological stimulus of peripheral blood T-cells .", "annotated_text": "p50 DNA-binding activity apparently stays highly controlled when p105 expression is enhanced by a physiological stimulus of <cell_type>peripheral blood T-cells</cell_type> ."}
{"id": "3750", "text": "Partial inhibition of p50 and p105 expression by NF-kappa B1 antisense oligonucleotides significantly reduced T-cell proliferation and CD25/IL-2R alpha cell surface expression .", "annotated_text": "Partial inhibition of p50 and p105 expression by <protein>NF-kappa B1</protein> antisense oligonucleotides significantly reduced T-cell proliferation and <protein>CD25/IL-2R alpha</protein> cell surface expression ."}
{"id": "3751", "text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "annotated_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"}
{"id": "3752", "text": "Vitamin D receptor quantitation in human blood mononuclear cells in health and disease .", "annotated_text": "<protein>Vitamin D receptor</protein> quantitation in <cell_type>human blood mononuclear cells</cell_type> in health and disease ."}
{"id": "3753", "text": "Vitamin D receptor ( VDR ) concentration was quantitated in human peripheral blood mononuclear cells ( PBMC ) from patients with absorptive hypercalciuria ( AH ) and patients with high 1 , 25 ( OH ) 2D3 due to acquired or transient disease states and the results compared to those in normal subjects .", "annotated_text": "<protein>Vitamin D receptor</protein> ( VDR ) concentration was quantitated in <cell_type>human peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) from patients with absorptive hypercalciuria ( AH ) and patients with high 1 , 25 ( OH ) 2D3 due to acquired or transient disease states and the results compared to those in normal subjects ."}
{"id": "3754", "text": "VDR concentration in resting cells was not different between the three groups and represented constitutive receptor expression of monocytes .", "annotated_text": "VDR concentration in <cell_type>resting cells</cell_type> was not different between the three groups and represented constitutive receptor expression of <cell_type>monocytes</cell_type> ."}
{"id": "3755", "text": "Following activation with phytohemagglutinin , patients with hypercalcitriolemia demonstrated significantly greater VDR concentrations .", "annotated_text": "Following activation with <protein>phytohemagglutinin</protein> , <cell_type>patients</cell_type> with hypercalcitriolemia demonstrated significantly greater VDR concentrations ."}
{"id": "3756", "text": "Patients with AH demonstrated a normal value for the group , but 6 patients had significantly greater concentrations of VDR despite normal plasma 1 , 25 ( OH ) 2D3 in four of the patients .", "annotated_text": "Patients with AH demonstrated a normal value for the group , but 6 patients had significantly greater concentrations of <protein>VDR</protein> despite normal plasma 1 , 25 ( OH ) 2D3 in four of the patients ."}
{"id": "3757", "text": "Proliferation , as assessed from [ 3H ] thymidine incorporation was inversely correlated with serum 1 , 25 ( OH ) 2D3 and was significant ( R = -0.299 , p = 0.048 ) .", "annotated_text": "Proliferation , as assessed from [ 3H ] thymidine incorporation was inversely correlated with serum 1 , 25 ( OH ) 2D3 and was significant ( R = -0.299 , p = 0.048 ) ."}
{"id": "3758", "text": "Taken together , the results suggest that PBMC provide a useful system for studying VDR status in transient or acquired states of hypercalcitriolemia .", "annotated_text": "Taken together , the results suggest that <cell_type>PBMC</cell_type> provide a useful system for studying <protein>VDR</protein> status in transient or acquired states of hypercalcitriolemia ."}
{"id": "3759", "text": "Furthermore , the studies in patients with absorptive hypercalciuria disclosed it to be a heterogeneous disorder , characterized by both vitamin D-dependent and D-independent forms of receptor up-regulation .", "annotated_text": "Furthermore , the studies in patients with absorptive hypercalciuria disclosed it to be a heterogeneous disorder , characterized by both vitamin D-dependent and D-independent forms of receptor up-regulation ."}
{"id": "3760", "text": "Reactive oxygen intermediates activate NF-kappa B in a tyrosine kinase-dependent mechanism and in combination with vanadate activate the p56lck and p59fyn tyrosine kinases in human lymphocytes .", "annotated_text": "Reactive oxygen intermediates activate <protein>NF-kappa B</protein> in a tyrosine kinase-dependent mechanism and in combination with vanadate activate the <protein>p56lck and p59fyn tyrosine kinases</protein> in <cell_type>human lymphocytes</cell_type> ."}
{"id": "3761", "text": "We have previously observed that ionizing radiation induces tyrosine phosphorylation in human B-lymphocyte precursors by stimulation of unidentified tyrosine kinases and this phosphorylation is substantially augmented by vanadate .", "annotated_text": "We have previously observed that ionizing radiation induces tyrosine phosphorylation in <cell_type>human B-lymphocyte precursors</cell_type> by stimulation of unidentified <protein>tyrosine kinases</protein> and this phosphorylation is substantially augmented by vanadate ."}
{"id": "3762", "text": "Ionizing radiation generates reactive oxygen intermediates ( ROI ) .", "annotated_text": "Ionizing radiation generates reactive oxygen intermediates ( ROI ) ."}
{"id": "3763", "text": "Because H2O2 is a potent ROI generator that readily crosses the plasma membrane , we used H2O2 to examine the effects of ROI on signal transduction .", "annotated_text": "Because H2O2 is a potent ROI generator that readily crosses the plasma membrane , we used H2O2 to examine the effects of ROI on signal transduction ."}
{"id": "3764", "text": "We now provide evidence that the tyrosine kinase inhibitor herbimycin A and the free radical scavenger N-acetyl-cysteine inhibit both radiation-induced and H2O2-induced activation of NF-kappa B , indicating that activation triggered by ROI is dependent on tyrosine kinase activity .", "annotated_text": "We now provide evidence that the tyrosine kinase inhibitor herbimycin A and the free radical scavenger N-acetyl-cysteine inhibit both radiation-induced and H2O2-induced activation of <protein>NF-kappa B</protein> , indicating that activation triggered by ROI is dependent on tyrosine kinase activity ."}
{"id": "3765", "text": "H2O2 was found to stimulate Ins-1 , 4 , 5-P3 production in a tyrosine kinase-dependent manner and to induce calcium signals that were greatly augmented by vanadate .", "annotated_text": "H2O2 was found to stimulate <protein>Ins-1 , 4 , 5-P3</protein> production in a tyrosine kinase-dependent manner and to induce calcium signals that were greatly augmented by vanadate ."}
{"id": "3766", "text": "The synergistic induction of tyrosine phosphorylation by H2O2 plus vanadate included physiologically relevant proteins such as PLC gamma 1 .", "annotated_text": "The synergistic induction of tyrosine phosphorylation by H2O2 plus vanadate included physiologically relevant proteins such as <protein>PLC gamma 1</protein> ."}
{"id": "3767", "text": "Although treatment of cells with H2O2 alone did not affect the activity of src family kinases , treatment with H2O2 plus vanadate led to activation of the p56lck and p59fyn tyrosine kinases .", "annotated_text": "Although treatment of cells with H2O2 alone did not affect the activity of <protein>src family kinases</protein> , treatment with H2O2 plus vanadate led to activation of the <protein>p56lck and p59fyn tyrosine kinases</protein> ."}
{"id": "3768", "text": "The combined inhibition of phosphatases and activation of kinases provides a potent mechanism for the synergistic effects of H2O2 plus vanadate .", "annotated_text": "The combined inhibition of <protein>phosphatases</protein> and activation of <protein>kinases</protein> provides a potent mechanism for the synergistic effects of H2O2 plus vanadate ."}
{"id": "3769", "text": "Induction of tyrosine phosphorylation by ROI may thus lead to many of the pleiotropic effects of ROI in lymphoid cells , including downstream activation of PLC gamma 1 and NF-kappa B", "annotated_text": "Induction of tyrosine phosphorylation by ROI may thus lead to many of the pleiotropic effects of ROI in <cell_type>lymphoid cells</cell_type> , including downstream activation of <protein>PLC gamma 1</protein> and <protein>NF-kappa B</protein>"}
{"id": "3770", "text": "Influence of sex hormone binding globulin and serum albumin on the conversion of androstenedione to testosterone by human erythrocytes .", "annotated_text": "Influence of <protein>sex hormone binding globulin</protein> and <protein>serum albumin</protein> on the conversion of androstenedione to testosterone by <cell_type>human erythrocytes</cell_type> ."}
{"id": "3771", "text": "The influence of human serum albumin and sex hormone binding globulin ( SHBG ) on the enzymic conversion of androstenedione to testosterone in human erythrocytes was investigated in vitro .", "annotated_text": "The influence of <protein>human serum albumin</protein> and <protein>sex hormone binding globulin</protein> ( <protein>SHBG</protein> ) on the enzymic conversion of androstenedione to testosterone in <cell_type>human erythrocytes</cell_type> was investigated in vitro ."}
{"id": "3772", "text": "Total plasma and albumin delayed the conversion rate of androstenedione , while SHBG increased it markedly .", "annotated_text": "Total plasma and <protein>albumin</protein> delayed the conversion rate of androstenedione , while <protein>SHBG</protein> increased it markedly ."}
{"id": "3773", "text": "The effect of SHBG was largely abolished by heating to 60 degrees C for 1 h and by saturating its binding sites by DHT .", "annotated_text": "The effect of <protein>SHBG</protein> was largely abolished by heating to 60 degrees C for 1 h and by saturating its binding sites by DHT ."}
{"id": "3774", "text": "The effect of both proteins was found to be related to their concentration .", "annotated_text": "The effect of both proteins was found to be related to their concentration ."}
{"id": "3775", "text": "It appears that the binding sites of albumin provide a mechanism for retarding androstenedione uptake by the erythrocytes and that the high binding affinity of SHBG for testosterone facilitates the diffusion of this steroid out of the cell and thus , displaces the chemical equilibrium within the cell .", "annotated_text": "It appears that the binding sites of <protein>albumin</protein> provide a mechanism for retarding androstenedione uptake by the <cell_type>erythrocytes</cell_type> and that the high binding affinity of <protein>SHBG</protein> for testosterone facilitates the diffusion of this steroid out of the cell and thus , displaces the chemical equilibrium within the cell ."}
{"id": "3776", "text": "Glucocorticoids and lymphocytes .", "annotated_text": "Glucocorticoids and <cell_type>lymphocytes</cell_type> ."}
{"id": "3777", "text": "I .", "annotated_text": "I ."}
{"id": "3778", "text": "Increased glucocorticoid receptor levels in antigen-stimulated lymphocytes .", "annotated_text": "Increased <protein>glucocorticoid receptor</protein> levels in <cell_line>antigen-stimulated lymphocytes</cell_line> ."}
{"id": "3779", "text": "Recently a 2- to 3-fold increase in the number of glucocorticoid receptors in human peripheral lymphocytes has been noted after in vitro mitogen stimulation .", "annotated_text": "Recently a 2- to 3-fold increase in the number of <protein>glucocorticoid receptors</protein> in <cell_type>human peripheral lymphocytes</cell_type> has been noted after in vitro mitogen stimulation ."}
{"id": "3780", "text": "Here , we extend these observations to in vivo immunization .", "annotated_text": "Here , we extend these observations to in vivo immunization ."}
{"id": "3781", "text": "After unilateral immunization of adrenalectomized male rats , a 50 % increase in glucocorticoid receptor sites per cell , determined by binding of dexamethasone , was observed in cell suspensions of homolateral lymph nodes over those from the contralateral nonimmunized side of the same animal .", "annotated_text": "After unilateral immunization of adrenalectomized male rats , a 50 % increase in glucocorticoid receptor sites per cell , determined by binding of dexamethasone , was observed in cell suspensions of homolateral lymph nodes over those from the contralateral nonimmunized side of the same animal ."}
{"id": "3782", "text": "The association constant for dexamethasone was similar in both groups , as was the stereospecificity for various steroids , the time course of cytoplasmic and nuclear association , and cytoplasmic-to-nuclear translocation .", "annotated_text": "The association constant for dexamethasone was similar in both groups , as was the stereospecificity for various steroids , the time course of cytoplasmic and nuclear association , and cytoplasmic-to-nuclear translocation ."}
{"id": "3783", "text": "Despite a 50 % increase in the number of glucocorticoid receptor sites per cell , the cells from the homolateral and controlateral lymph nodes were equally sensitive to the inhibitory effects of dexamethasone , as determined by measurements of the incorporation of radiolabeled precursors of protein , RNA , and DNA , or measurements of in vitro cell survival .", "annotated_text": "Despite a 50 % increase in the number of glucocorticoid receptor sites per cell , the cells from the homolateral and controlateral lymph nodes were equally sensitive to the inhibitory effects of dexamethasone , as determined by measurements of the incorporation of radiolabeled precursors of protein , RNA , and DNA , or measurements of in vitro cell survival ."}
{"id": "3784", "text": "Glucocorticoid receptors and actions in rat thymocytes and immunologically stimulated human peripheral lymphocytes .", "annotated_text": "Glucocorticoid receptors and actions in <cell_type>rat thymocytes</cell_type> and immunologically stimulated <cell_type>human peripheral lymphocytes</cell_type> ."}
{"id": "3785", "text": "After reviewing briefly our earlier studies on glucocorticoid receptors and mechanisms in thymus cells , we have outlined results from the following two areas of current interest in our laboratories : the `` life-cycle '' of glucocorticoid receptors and complexes in thymus cells , and the levels of glucocorticoid receptors and sensitivity in immunologically stimulated human peripheral lymphocytes .", "annotated_text": "After reviewing briefly our earlier studies on glucocorticoid receptors and mechanisms in <cell_type>thymus cells</cell_type> , we have outlined results from the following two areas of current interest in our laboratories : the `` life-cycle '' of glucocorticoid receptors and complexes in <cell_type>thymus cells</cell_type> , and the levels of glucocorticoid receptors and sensitivity in <cell_type>immunologically stimulated human peripheral lymphocytes</cell_type> ."}
{"id": "3786", "text": "Several of our results on energetics and kinetics of hormone binding to glucocorticoid receptors in rat thymus cells seem to require extension of the simplest model of hormone-receptor transformations in intact cells .", "annotated_text": "Several of our results on energetics and kinetics of hormone binding to <protein>glucocorticoid receptors</protein> in <cell_type>rat thymus cells</cell_type> seem to require extension of the simplest model of hormone-receptor transformations in <cell_type>intact cells</cell_type> ."}
{"id": "3787", "text": "ATP-depletion experiments suggest the existence of a nonbinding form of the receptor ; `` chase '' experiments suggest reaction of hormone directly with nuclear-bound receptor ; experiments on depletion and replenishment of cytoplasmic receptor using cortisol and dexamethasone suggest the existence of at least two subpopulations of nuclear-bound hormone-receptor complex .", "annotated_text": "ATP-depletion experiments suggest the existence of a nonbinding form of the receptor ; `` chase '' experiments suggest reaction of hormone directly with nuclear-bound receptor ; experiments on depletion and replenishment of <protein>cytoplasmic receptor</protein> using cortisol and dexamethasone suggest the existence of at least two subpopulations of <protein>nuclear-bound hormone-receptor complex</protein> ."}
{"id": "3788", "text": "We have found that mitogen or immunologic stimulation of human peripheral lymphocytes in culture leads within 24 h or so to a striking increase in the number of glucocorticoid receptor sites per cell .", "annotated_text": "We have found that mitogen or immunologic stimulation of <cell_type>human peripheral lymphocytes</cell_type> in culture leads within 24 h or so to a striking increase in the number of <protein>glucocorticoid receptor</protein> sites per cell ."}
{"id": "3789", "text": "We believe this increase may be due to partial synchronization of the cell population in a phase of the cell cycle in which receptor content is high .", "annotated_text": "We believe this increase may be due to partial synchronization of the cell population in a phase of the cell cycle in which receptor content is high ."}
{"id": "3790", "text": "Contrary to the widely held view that mitogen-stimulated cells become insensitive to glucocorticoids , our experiments show that with respect to inhibition of thymidine and uridine incorporation and glucose uptake , the cells are highly sensitive to dexamethasone at 24 , 48 , and 72 h after stimulation with concanavalin A .", "annotated_text": "Contrary to the widely held view that <cell_type>mitogen-stimulated cells</cell_type> become insensitive to glucocorticoids , our experiments show that with respect to inhibition of thymidine and uridine incorporation and glucose uptake , the cells are highly sensitive to dexamethasone at 24 , 48 , and 72 h after stimulation with <protein>concanavalin A</protein> ."}
{"id": "3791", "text": "Nuclear glucocorticoid binding in chronic lymphatic leukemia lymphocytes .", "annotated_text": "Nuclear glucocorticoid binding in <cell_type>chronic lymphatic leukemia lymphocytes</cell_type> ."}
{"id": "3792", "text": "A reliable procedure is described for isolating 3H-triamcinolone acetonide ( 3H-TA ) receptor complexes from purified chronic lymphatic leukemia ( CLL ) lymphocyte nuclei , based on the use of carbobenzoxy-L-phenylalanine ( CBZ-L-phe ) to prevent breakdown of hormone-receptor complexes during extraction of nuclei with 0.6M KCl .", "annotated_text": "A reliable procedure is described for isolating <protein>3H-triamcinolone acetonide ( 3H-TA ) receptor complexes</protein> from purified chronic <cell_type>lymphatic leukemia ( CLL ) lymphocyte</cell_type> nuclei , based on the use of carbobenzoxy-L-phenylalanine ( CBZ-L-phe ) to prevent breakdown of <protein>hormone-receptor complexes</protein> during extraction of nuclei with 0.6M KCl ."}
{"id": "3793", "text": "Using this method , specific nuclear glucocorticoid binding was demonstrated in 14/14 patients with untreated CLL .", "annotated_text": "Using this method , specific nuclear glucocorticoid binding was demonstrated in 14/14 patients with untreated CLL ."}
{"id": "3794", "text": "No correlation was found between levels of nuclear-associated 3H-TA and peripheral white blood cell count or rosetting ability of circulating lymphocytes .", "annotated_text": "No correlation was found between levels of nuclear-associated 3H-TA and peripheral white blood cell count or rosetting ability of <cell_type>circulating lymphocytes</cell_type> ."}
{"id": "3795", "text": "Multiple closely-linked NFAT/octamer and HMG I ( Y ) binding sites are part of the interleukin-4 promoter .", "annotated_text": "Multiple closely-linked <dna>NFAT/octamer</dna> and <dna>HMG I ( Y ) binding sites</dna> are part of the interleukin-4 promoter ."}
{"id": "3796", "text": "We show here that the immediate upstream region ( from position -12 to -270 ) of the murine interleukin 4 ( Il-4 ) gene harbors a strong cell-type specific transcriptional enhancer .", "annotated_text": "We show here that the <dna>immediate upstream region</dna> ( from position -12 to -270 ) of the <dna>murine interleukin 4 ( Il-4 ) gene</dna> harbors a strong cell-type specific <dna>transcriptional enhancer</dna> ."}
{"id": "3797", "text": "In T lymphoma cells , the activity of the Il-4 promoter/enhancer is stimulated by phorbol esters , Ca++ ionophores and agonists of protein kinase A and inhibited by low doses of the immunosuppressant cyclosporin A .", "annotated_text": "In <cell_type>T lymphoma cells</cell_type> , the activity of the <dna>Il-4 promoter/enhancer</dna> is stimulated by phorbol esters , Ca++ ionophores and agonists of <protein>protein kinase A</protein> and inhibited by low doses of the immunosuppressant cyclosporin A ."}
{"id": "3798", "text": "The Il-4 promoter/enhancer is transcriptionally inactive in B lymphoma cells and HeLa cells .", "annotated_text": "The <dna>Il-4 promoter/enhancer</dna> is transcriptionally inactive in <cell_type>B lymphoma cells</cell_type> and <cell_type>HeLa cells</cell_type> ."}
{"id": "3799", "text": "DNase I footprint protection experiments revealed six sites of the Il-4 promoter/enhancer to be bound by nuclear proteins from lymphoid and myeloid cells .", "annotated_text": "DNase I footprint protection experiments revealed six sites of the <dna>Il-4 promoter/enhancer</dna> to be bound by <protein>nuclear proteins</protein> from <cell_type>lymphoid and myeloid cells</cell_type> ."}
{"id": "3800", "text": "Among them are four purine boxes which have been described to be important sequence motifs of the Il-2 promoter .", "annotated_text": "Among them are four purine boxes which have been described to be important sequence motifs of the <dna>Il-2 promoter</dna> ."}
{"id": "3801", "text": "They contain the motif GGAAA and are recognized by the inducible and cyclosporin A-sensitive transcription factor NFAT-1 .", "annotated_text": "They contain the motif GGAAA and are recognized by the <protein>inducible and cyclosporin A-sensitive transcription factor NFAT-1</protein> ."}
{"id": "3802", "text": "Three of the Il-4 NFAT-1 sites are closely linked to weak binding sites of Octamer factors .", "annotated_text": "Three of the <dna>Il-4 NFAT-1 sites</dna> are closely linked to weak binding sites of <protein>Octamer factors</protein> ."}
{"id": "3803", "text": "Several purine boxes and an AT-rich protein-binding site of the Il-4 promoter are also recognized by the high mobility group protein HMG I ( Y ) .", "annotated_text": "Several purine boxes and an <dna>AT-rich protein-binding site</dna> of the Il-4 promoter are also recognized by the <protein>high mobility group protein</protein> <protein>HMG I ( Y</protein> ) ."}
{"id": "3804", "text": "Whereas the binding of NFAT-1 and Octamer factors enhance the activity of the Il-4 promoter , the binding of HMG I ( Y ) suppresses its activity and , therefore , appears to be involved in the suppression of Il-4 transcription in resting T lymphocytes .", "annotated_text": "Whereas the binding of <protein>NFAT-1</protein> and <protein>Octamer factors</protein> enhance the activity of the <dna>Il-4 promoter</dna> , the binding of HMG I ( Y ) suppresses its activity and , therefore , appears to be involved in the suppression of <protein>Il-4</protein> transcription in <cell_type>resting T lymphocytes</cell_type> ."}
{"id": "3805", "text": "Reversibility of the differentiated state in somatic cells .", "annotated_text": "Reversibility of the differentiated state in <cell_type>somatic cells</cell_type> ."}
{"id": "3806", "text": "Analysis of de novo gene activation in multinucleated heterokaryons has shown that the differentiated state , although stable , is not irreversible , and can be reprogrammed in the presence of appropriate combinations of trans-acting regulatory molecules .", "annotated_text": "Analysis of de novo gene activation in <cell_type>multinucleated heterokaryons</cell_type> has shown that the differentiated state , although stable , is not irreversible , and can be reprogrammed in the presence of appropriate combinations of <protein>trans-acting regulatory molecules</protein> ."}
{"id": "3807", "text": "These properties have been exploited to design strategies for identifying novel regulators of cellular differentiation .", "annotated_text": "These properties have been exploited to design strategies for identifying novel regulators of cellular differentiation ."}
{"id": "3808", "text": "Phosphatidylcholine hydrolysis activates NF-kappa B and increases human immunodeficiency virus replication in human monocytes and T lymphocytes .", "annotated_text": "Phosphatidylcholine hydrolysis activates <protein>NF-kappa B</protein> and increases human immunodeficiency virus replication in <cell_type>human monocytes</cell_type> and <cell_type>T lymphocytes</cell_type> ."}
{"id": "3809", "text": "We have tested whether breakdown of phosphatidylcholine ( PC ) initiated by exogenous addition of a PC-specific phospholipase C ( PC-PLC ) from Bacillus cereus or by endogenous overexpression of PC-PLC induces functional activation of NF-kappa B and increases human immunodeficiency virus ( HIV ) enhancer activity .", "annotated_text": "We have tested whether breakdown of phosphatidylcholine ( PC ) initiated by exogenous addition of a <protein>PC-specific phospholipase C</protein> ( <protein>PC-PLC</protein> ) from Bacillus cereus or by endogenous overexpression of <protein>PC-PLC</protein> induces functional activation of <protein>NF-kappa B</protein> and increases <dna>human immunodeficiency virus ( HIV ) enhancer</dna> activity ."}
{"id": "3810", "text": "PC-PLC-activated hydrolysis of PC was found to induce bona fide p50/p65 NF-kappa B binding activity in three different cell lines of human or murine origin .", "annotated_text": "PC-PLC-activated hydrolysis of PC was found to induce bona fide <protein>p50/p65 NF-kappa B</protein> binding activity in three different <cell_line>cell lines</cell_line> of human or murine origin ."}
{"id": "3811", "text": "No significant changes in the turnover of other cellular phospholipids were detected in PC-PLC-treated cells .", "annotated_text": "No significant changes in the turnover of other cellular phospholipids were detected in <cell_line>PC-PLC-treated cells</cell_line> ."}
{"id": "3812", "text": "Induction of NF-kappa B by PC-PLC did not depend on de novo synthesis of proteins or autocrine secretion of either tumor necrosis factor or interleukin 1 .", "annotated_text": "Induction of <protein>NF-kappa B</protein> by <protein>PC-PLC</protein> did not depend on de novo synthesis of proteins or autocrine secretion of either <protein>tumor necrosis factor</protein> or <protein>interleukin 1</protein> ."}
{"id": "3813", "text": "In human monocytic and lymphoblastoid T-cell lines , induction of NF-kappa B by PC-PLC resulted in clear induction of luciferase expression vectors placed under the control of synthetic kappa B enhancers or wild type , but not kappa B-mutated , HIV long terminal repeat constructs .", "annotated_text": "In <cell_line>human monocytic and lymphoblastoid T-cell lines</cell_line> , induction of <protein>NF-kappa B</protein> by <protein>PC-PLC</protein> resulted in clear induction of <protein>luciferase</protein> expression vectors placed under the control of <dna>synthetic kappa B enhancers</dna> or wild type , but not kappa B-mutated , <dna>HIV long terminal repeat constructs</dna> ."}
{"id": "3814", "text": "HIV replication was increased by PC-PLC in chronically infected monocytes and T lymphocytes .", "annotated_text": "HIV replication was increased by <protein>PC-PLC</protein> in chronically infected <cell_type>monocytes</cell_type> and T <cell_type>lymphocytes</cell_type> ."}
{"id": "3815", "text": "NF-kappa B activation promoted by addition of exogenous PC-PLC correlated with an intense production of diacylglycerol .", "annotated_text": "NF-kappa B activation promoted by addition of <protein>exogenous PC-PLC</protein> correlated with an intense production of diacylglycerol ."}
{"id": "3816", "text": "However , addition of a phosphatidylinositol-specific PLC from B.cereus also induced diacylglycerol but did not activate kappa B enhancer-directed vectors .", "annotated_text": "However , addition of a <protein>phosphatidylinositol-specific PLC</protein> from B.cereus also induced diacylglycerol but did not activate <protein>kappa B enhancer-directed vectors</protein> ."}
{"id": "3817", "text": "PC-PLC-induced NF-kappa B activation could not be blocked by a specific inhibitor of phorbol ester-inducible protein kinases C .", "annotated_text": "PC-PLC-induced NF-kappa B activation could not be blocked by a specific inhibitor of <protein>phorbol ester-inducible protein kinases C</protein> ."}
{"id": "3818", "text": "These results indicate that a cellular transduction pathway , dependent on specific PC breakdown , is functional in T lymphocytes and monocytes and may be used by various transmembrane receptors to activate HIV transcription through NF-kappa B-dependent induction of the HIV enhancer .", "annotated_text": "These results indicate that a cellular transduction pathway , dependent on specific PC breakdown , is functional in <cell_type>T lymphocytes</cell_type> and <cell_type>monocytes</cell_type> and may be used by various transmembrane receptors to activate HIV transcription through NF-kappa B-dependent induction of the <dna>HIV enhancer</dna> ."}
{"id": "3819", "text": "Novel mechanism for inhibition of human T cells by glucocorticoids .", "annotated_text": "Novel mechanism for inhibition of <cell_type>human T cells</cell_type> by glucocorticoids ."}
{"id": "3820", "text": "Glucocorticoids inhibit signal transduction through IL-2 receptor .", "annotated_text": "Glucocorticoids inhibit signal transduction through <protein>IL-2 receptor</protein> ."}
{"id": "3821", "text": "Interaction of IL-2 with its high affinity membrane receptor complex ( IL-2R ) present on activated T lymphocytes induces cell proliferation and mediates effector functions .", "annotated_text": "Interaction of <protein>IL-2</protein> with its <protein>high affinity membrane receptor complex</protein> ( <protein>IL-2R</protein> ) present on activated <cell_type>T lymphocytes</cell_type> induces cell proliferation and mediates effector functions ."}
{"id": "3822", "text": "Glucocorticoids inhibit IL-2 production by inhibiting TCR-mediated signal transduction .", "annotated_text": "Glucocorticoids inhibit <protein>IL-2</protein> production by inhibiting TCR-mediated signal transduction ."}
{"id": "3823", "text": "We asked whether they also inhibit the action of IL-2 by inhibiting signal transduction through IL-2R .", "annotated_text": "We asked whether they also inhibit the action of <protein>IL-2</protein> by inhibiting signal transduction through <protein>IL-2R</protein> ."}
{"id": "3824", "text": "Human peripheral blood T cells , stimulated with PMA for 48 h ( PMA blasts ) , were incubated with IL-2 in the presence of incremental dosages of dexamethasone ( Dex ; 10 ( -5 ) -10 ( -9 ) M ) .", "annotated_text": "<cell_type>Human peripheral blood T cells</cell_type> , stimulated with PMA for 48 h ( <cell_line>PMA blasts</cell_line> ) , were incubated with <protein>IL-2</protein> in the presence of incremental dosages of dexamethasone ( Dex ; 10 ( -5 ) -10 ( -9 ) M ) ."}
{"id": "3825", "text": "Dex inhibited the IL-2-dependent proliferation of PMA blasts in a dose-dependent fashion ( IC50 , 5 x 10 ( -8 ) M ) .", "annotated_text": "Dex inhibited the IL-2-dependent proliferation of <cell_line>PMA blasts</cell_line> in a dose-dependent fashion ( IC50 , 5 x 10 ( -8 ) M ) ."}
{"id": "3826", "text": "Cell surface expression of IL-2R alpha- and beta-chains as determined by immunofluorescence analysis was not affected by Dex .", "annotated_text": "Cell surface expression of <protein>IL-2R alpha- and beta-chains</protein> as determined by immunofluorescence analysis was not affected by Dex ."}
{"id": "3827", "text": "In addition , Scatchard plot analysis of 125I-labeled IL-2 showed that Dex did not affect the binding of IL-2 , thus suggesting that inhibition is due to a postreceptor effect .", "annotated_text": "In addition , Scatchard plot analysis of <protein>125I-labeled IL-2</protein> showed that Dex did not affect the binding of <protein>IL-2</protein> , thus suggesting that inhibition is due to a postreceptor effect ."}
{"id": "3828", "text": "Inhibition of T cell proliferation by Dex was associated with decreased IL-2-dependent tyrosine phosphorylation of several intracellular proteins and decreased phosphorylation of the retinoblastoma gene product Rb , a protein essential for controlling the progression of cells through the cell cycle .", "annotated_text": "Inhibition of T cell proliferation by Dex was associated with decreased IL-2-dependent tyrosine phosphorylation of several <protein>intracellular proteins</protein> and decreased phosphorylation of the <protein>retinoblastoma gene product Rb</protein> , a protein essential for controlling the progression of cells through the cell cycle ."}
{"id": "3829", "text": "IL-2-dependent IL-2R alpha expression in PMA blasts and NF-kB induction in resting human T cells were also inhibited by Dex .", "annotated_text": "IL-2-dependent IL-2R alpha expression in <cell_line>PMA blasts</cell_line> and <protein>NF-kB</protein> induction in <cell_type>resting human T cells</cell_type> were also inhibited by Dex ."}
{"id": "3830", "text": "These results demonstrate that glucocorticoids inhibit preactivated T cells by down-regulating signal transduction through IL-2R .", "annotated_text": "These results demonstrate that glucocorticoids inhibit <cell_line>preactivated T cells</cell_line> by down-regulating signal transduction through <protein>IL-2R</protein> ."}
{"id": "3831", "text": "Chronic human immunodeficiency virus type 1 infection stimulates distinct NF-kappa B/rel DNA binding activities in myelomonoblastic cells .", "annotated_text": "Chronic human immunodeficiency virus type 1 infection stimulates distinct NF-kappa B/rel DNA binding activities in <cell_type>myelomonoblastic cells</cell_type> ."}
{"id": "3832", "text": "The relationship between human immunodeficiency virus type 1 ( HIV-1 ) infection and the induction of NF-kappa B binding activity was examined in a myeloid cell model of HIV-1 infection derived from the PLB-985 cell line .", "annotated_text": "The relationship between human immunodeficiency virus type 1 ( HIV-1 ) infection and the induction of NF-kappa B binding activity was examined in a <cell_line>myeloid cell model</cell_line> of HIV-1 infection derived from the <cell_line>PLB-985 cell line</cell_line> ."}
{"id": "3833", "text": "Chronic infection of PLB-985 cells led to increased monocyte-specific surface marker expression , increased c-fms gene transcription , and morphological alterations consistent with differentiation along the monocytic pathway .", "annotated_text": "Chronic infection of <cell_line>PLB-985 cells</cell_line> led to increased monocyte-specific surface marker expression , increased c-fms gene transcription , and morphological alterations consistent with differentiation along the monocytic pathway ."}
{"id": "3834", "text": "PLB-IIIB cells displayed a constitutive NF-kappa B-like binding activity that was distinct from that induced by tumor necrosis factor alpha or phorbol 12-myristate 13-acetate treatment of the parental PLB-985 cell line .", "annotated_text": "<cell_line>PLB-IIIB cells</cell_line> displayed a constitutive NF-kappa B-like binding activity that was distinct from that induced by <protein>tumor necrosis factor alpha</protein> or phorbol 12-myristate 13-acetate treatment of the <cell_line>parental PLB-985 cell line</cell_line> ."}
{"id": "3835", "text": "This unique DNA binding activity consisted of proteins of 70 , 90 , and 100 kDa with a high degree of binding specificity for the NF-kappa B site within the PRDII domain of beta interferon .", "annotated_text": "This unique DNA binding activity consisted of proteins of <protein>70 , 90 , and 100 kDa</protein> with a high degree of binding specificity for the <protein>NF-kappa B site</protein> within the <protein>PRDII domain</protein> of <protein>beta interferon</protein> ."}
{"id": "3836", "text": "In this report , we characterize the nature of these proteins and demonstrate that binding of these proteins is also induced following Sendai paramyxovirus infection .", "annotated_text": "In this report , we characterize the nature of these proteins and demonstrate that binding of these proteins is also induced following Sendai paramyxovirus infection ."}
{"id": "3837", "text": "The 70-kDa protein corresponds to the NF-kappa B RelA ( p65 ) subunit , which is activated in response to an acute paramyxovirus infection or a chronic HIV-1 infection .", "annotated_text": "The <protein>70-kDa protein</protein> corresponds to the <protein>NF-kappa B RelA ( p65 ) subunit</protein> , which is activated in response to an acute paramyxovirus infection or a chronic HIV-1 infection ."}
{"id": "3838", "text": "Virus infection does not appear to alter the amount of RelA ( p65 ) or NFKB1 ( p50 ) but rather affects the capacity of I kappa B alpha to sequester RelA ( p65 ) , therefore leading to constitutive levels of RelA DNA binding activity and to increased levels of NF-kappa B-dependent gene activity .", "annotated_text": "Virus infection does not appear to alter the amount of <protein>RelA</protein> ( <protein>p65</protein> ) or <protein>NFKB1</protein> ( <protein>p50</protein> ) but rather affects the capacity of <protein>I kappa B alpha</protein> to sequester <protein>RelA ( p65 )</protein> , therefore leading to constitutive levels of RelA DNA binding activity and to increased levels of NF-kappa B-dependent gene activity ."}
{"id": "3839", "text": "The virally induced 90- to 100-kDa proteins have a distinct binding specificity for the PRDII domain and an AT-rich sequence but do not cross-react with NF-kappa B subunit-specific antisera directed against NFKB1 ( p105 or p50 ) , NFKB2 ( p100 or p52 ) , RelA ( p65 ) , or c-rel .", "annotated_text": "The virally induced <protein>90- to 100-kDa proteins</protein> have a distinct binding specificity for the <dna>PRDII domain</dna> and an <dna>AT-rich sequence</dna> but do not cross-react with NF-kappa B subunit-specific antisera directed against <protein>NFKB1</protein> ( <protein>p105</protein> or <protein>p50</protein> ) , <protein>NFKB2</protein> ( <protein>p100</protein> or <protein>p52</protein> ) , <protein>RelA</protein> ( <protein>p65</protein> ) , or <protein>c-rel</protein> ."}
{"id": "3840", "text": "DNA binding of the 90- to 100-kDa proteins was not inhibited by recombinant I kappa B alpha/MAD-3 and was resistant to tryptic digestion , suggesting that these proteins may not be NF-kappa B related .", "annotated_text": "DNA binding of the <protein>90- to 100-kDa proteins</protein> was not inhibited by <protein>recombinant I kappa B alpha/MAD-3</protein> and was resistant to tryptic digestion , suggesting that these proteins may not be <protein>NF-kappa B related</protein> ."}
{"id": "3841", "text": "Transient cotransfection experiments demonstrated that RelA and NFKB1 expression maximally stimulated HIV-1 LTR- and NF-kappa B-dependent reporter genes ; differences in NF-kappa B-like binding activity were also reflected in higher constitutive levels of NF-kappa B-regulated gene expression in HIV-1-infected myeloid cells .", "annotated_text": "Transient cotransfection experiments demonstrated that RelA and NFKB1 expression maximally stimulated <dna>HIV-1 LTR- and NF-kappa B-dependent reporter genes</dna> ; differences in NF-kappa B-like binding activity were also reflected in higher constitutive levels of NF-kappa B-regulated gene expression in <cell_line>HIV-1-infected myeloid cells</cell_line> ."}
{"id": "3842", "text": "Presence of estrogen-binding sites on macrophage-like synoviocytes and CD8+ , CD29+ , CD45RO+ T lymphocytes in normal and rheumatoid synovium .", "annotated_text": "Presence of estrogen-binding sites on <cell_type>macrophage-like synoviocytes</cell_type> and <cell_line>CD8+ , CD29+ , CD45RO+ T lymphocytes</cell_line> in normal and rheumatoid synovium ."}
{"id": "3843", "text": "OBJECTIVE .", "annotated_text": "OBJECTIVE ."}
{"id": "3844", "text": "To study the presence of estrogen-binding sites ( EBS ) in the synovial tissues of male and female patients with rheumatoid arthritis ( RA ) and in age- and sex-matched healthy controls .", "annotated_text": "To study the presence of estrogen-binding sites ( EBS ) in the synovial tissues of male and female patients with rheumatoid arthritis ( RA ) and in age- and sex-matched healthy controls ."}
{"id": "3845", "text": "METHODS .", "annotated_text": "METHODS ."}
{"id": "3846", "text": "Both type 1 ( high affinity , low binding capacity ) and type 2 ( reduced affinity , higher binding capacity ) EBS were investigated in both soluble and nuclear fractions of homogenized synovial tissue samples by a dextran-coated charcoal method .", "annotated_text": "Both type 1 ( high affinity , low binding capacity ) and type 2 ( reduced affinity , higher binding capacity ) EBS were investigated in both soluble and nuclear fractions of homogenized synovial tissue samples by a dextran-coated charcoal method ."}
{"id": "3847", "text": "To determine what type of synovial cell was positive for EBS , cryosections of synovial tissues were immunostained with a specific monoclonal anti-estrogen receptor antibody ( anti-ER MAb ) using both immunofluorescence and immunoperoxidase techniques .", "annotated_text": "To determine what type of <cell_type>synovial cell</cell_type> was positive for EBS , cryosections of synovial tissues were immunostained with a specific <protein>monoclonal anti-estrogen receptor antibody</protein> ( <protein>anti-ER MAb</protein> ) using both immunofluorescence and immunoperoxidase techniques ."}
{"id": "3848", "text": "Double immunostaining with the anti-ER MAb and with specific MAb to detect different macrophage antigens ( Ber-MAC3 , MAC387 , CD68 ) and CD8+ T cell subsets ( CD29+ , CD45RO+ and CD29- , CD45RO- ) was performed .", "annotated_text": "Double immunostaining with the <protein>anti-ER MAb</protein> and with <protein>specific MAb</protein> to detect different <protein>macrophage antigens</protein> ( <protein>Ber-MAC3</protein> , <protein>MAC387</protein> , <protein>CD68</protein> ) and <cell_line>CD8+ T cell subsets</cell_line> ( <cell_line>CD29+</cell_line> , <cell_line>CD45RO+</cell_line> and <cell_line>CD29-</cell_line> , <cell_line>CD45RO-</cell_line> ) was performed ."}
{"id": "3849", "text": "RESULTS .", "annotated_text": "RESULTS ."}
{"id": "3850", "text": "Higher affinity EBS were found mostly in nuclear cell fractions of either RA or control synovial tissues ( 28 of the 33 ) .", "annotated_text": "Higher affinity EBS were found mostly in nuclear cell fractions of either RA or control synovial tissues ( 28 of the 33 ) ."}
{"id": "3851", "text": "These EBS were present to a lesser extent in soluble cell fractions ( 11 of the 33 ) .", "annotated_text": "These EBS were present to a lesser extent in soluble cell fractions ( 11 of the 33 ) ."}
{"id": "3852", "text": "Immunostaining showed the estrogen receptor-positive cells to be the macrophage-like synoviocytes and the CD8+ , CD29+ T cells both in RA and in control synovial tissues .", "annotated_text": "Immunostaining showed the <cell_type>estrogen receptor-positive cells</cell_type> to be the <cell_type>macrophage-like synoviocytes</cell_type> and the <cell_line>CD8+</cell_line> , <cell_line>CD29+ T cells</cell_line> both in RA and in control synovial tissues ."}
{"id": "3853", "text": "Higher nuclear content of EBS was consistent with more intense nuclear staining of synoviocytes and T cells .", "annotated_text": "Higher nuclear content of EBS was consistent with more intense nuclear staining of <cell_type>synoviocytes</cell_type> and <cell_type>T cells</cell_type> ."}
{"id": "3854", "text": "CONCLUSION .", "annotated_text": "CONCLUSION ."}
{"id": "3855", "text": "It is conceivable that the immunomodulatory activity exerted by estrogens is at least partly mediated through their interaction with EBS that are present on macrophage-like synoviocytes , functioning as antigen-processing and antigen-presenting cells , and on antigen-experienced ( memory ) CD8+ T lymphocytes ( CD29+ , CD45RO+", "annotated_text": "It is conceivable that the immunomodulatory activity exerted by estrogens is at least partly mediated through their interaction with EBS that are present on <cell_type>macrophage-like synoviocytes</cell_type> , functioning as <cell_type>antigen-processing and antigen-presenting cells</cell_type> , and on <cell_line>antigen-experienced ( memory ) CD8+ T lymphocytes</cell_line> ( <cell_line>CD29+</cell_line> , <cell_line>CD45RO+</cell_line>"}