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500 | Retinoic acid ( RA ) , a vitamin A derivative , exerts a wide range of biological effects related to cell proliferation and differentiation . | Retinoic acid ( RA ) , a vitamin A derivative , exerts a wide range of biological effects related to cell proliferation and differentiation . |
501 | The pleiotropic effects of RA are thought to be mediated through specific nuclear RA receptors ( RARs ) . | The pleiotropic effects of RA are thought to be mediated through specific nuclear <protein>RA receptors</protein> ( <protein>RARs</protein> ) . |
502 | RARs are members of the steroid/thyroid hormone receptor superfamily and exhibit a molecular structure that possess discrete DNA-binding and RA ( ligand ) -binding domains . | <protein>RARs</protein> are members of the <protein>steroid/thyroid hormone receptor superfamily</protein> and exhibit a molecular structure that possess discrete DNA-binding and <protein>RA ( ligand ) -binding domains</protein> . |
503 | In hematopoietic system , RA and RARs , predominantly RAR alpha may play key roles for the proliferation and differentiation of hematopoietic progenitors . | In hematopoietic system , RA and <protein>RARs</protein> , predominantly <protein>RAR alpha</protein> may play key roles for the proliferation and differentiation of <cell_type>hematopoietic progenitors</cell_type> . |
504 | However , it is currently unknown how RA and RARs are involved in regulating normal hematopoietic differentiation . | However , it is currently unknown how RA and <protein>RARs</protein> are involved in regulating normal hematopoietic differentiation . |
505 | To make clear the roles of RA and RAR alpha in the normal hematopoiesis , I have introduced the construct of human RAR alpha ( hRAR alpha ) into murine bone marrow cells with retroviral vector , and selected infected cells with drug resistant marker ( Neo ( r ) ) cultured on the stroma cell line ( PA6-neo ) , and analyzed the behavior of infected cells . | To make clear the roles of RA and <protein>RAR alpha</protein> in the normal hematopoiesis , I have introduced the construct of <protein>human RAR alpha</protein> ( <protein>hRAR alpha</protein> ) into <cell_type>murine bone marrow cells</cell_type> with retroviral vector , and selected infected cells with <dna>drug resistant marker</dna> ( <dna>Neo ( r )</dna> ) cultured on the <cell_line>stroma cell line</cell_line> ( <cell_line>PA6-neo</cell_line> ) , and analyzed the behavior of <cell_type>infected cells</cell_type> . |
506 | All of procedure were done in vitro . | All of procedure were done in vitro . |
507 | Most cells infected with hRAR alpha exhibited promyelocytic morphology and were thought to be blocked at the promyelocytic stage in their myeloid differentiation . | Most cells infected with <protein>hRAR alpha</protein> exhibited <cell_type>promyelocytic morphology</cell_type> and were thought to be blocked at the promyelocytic stage in their myeloid differentiation . |
508 | Furthermore , these immature cells differentiated terminally into mature granulocytes by adding with RA ( 10 ( -6 ) M ) . | Furthermore , these <cell_type>immature cells</cell_type> differentiated terminally into mature granulocytes by adding with RA ( 10 ( -6 ) M ) . |
509 | RAR alpha infected cells were also able to differentiate into mature macrophages in the both of long term culture and IL3 colony . | <protein>RAR alpha</protein> <cell_type>infected cells</cell_type> were also able to differentiate into <cell_type>mature macrophages</cell_type> in the both of long term culture and <cell_line>IL3 colony</cell_line> . |
510 | These observations suggest that an overexpression of RAR alpha alone is effective to suppress myeloid cell differentiation and RAR alpha plays a crucial role in the terminal differentiation of myeloid precursors . | These observations suggest that an overexpression of <protein>RAR alpha</protein> alone is effective to suppress <cell_type>myeloid cell</cell_type> differentiation and <protein>RAR alpha</protein> plays a crucial role in the terminal differentiation of myeloid precursors . |
511 | The system described here may serve as a model for studying the the essential genes for differentiation of normal bone marrow cells . | The system described here may serve as a model for studying the the <dna>essential genes</dna> for differentiation of <cell_type>normal bone marrow cells</cell_type> . |
512 | Hypoxic induction of interleukin-8 gene expression in human endothelial cells . | Hypoxic induction of <dna>interleukin-8 gene</dna> expression in <cell_type>human endothelial cells</cell_type> . |
513 | Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion , we have sought mechanisms by which PMNs are directed into hypoxic tissue . | Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion , we have sought mechanisms by which <cell_type>PMNs</cell_type> are directed into hypoxic tissue . |
514 | Incubation of human endothelial cells ( ECs ) in hypoxia , PO2 approximately 14-18 Torr , led to time-dependent release of IL-8 antigen into the conditioned medium ; this was accompanied by increased chemotactic activity for PMNs , blocked by antibody to IL-8 . | Incubation of <cell_type>human endothelial cells</cell_type> ( <cell_type>ECs</cell_type> ) in hypoxia , PO2 approximately 14-18 Torr , led to time-dependent release of <protein>IL-8</protein> antigen into the conditioned medium ; this was accompanied by increased chemotactic activity for <cell_type>PMNs</cell_type> , blocked by antibody to <protein>IL-8</protein> . |
515 | Production of IL-8 by hypoxic ECs occurred concomitantly with both increased levels of IL-8 mRNA , based on polymerase chain reaction analysis , and increased IL-8 transcription , based on nuclear run-on assays . | Production of <protein>IL-8</protein> by hypoxic <cell_type>ECs</cell_type> occurred concomitantly with both increased levels of <rna>IL-8 mRNA</rna> , based on polymerase chain reaction analysis , and increased <protein>IL-8</protein> transcription , based on nuclear run-on assays . |
516 | Northern analysis of mRNA from hypoxic ECs also demonstrated increased levels of mRNA for macrophage chemotactic protein-1 , another member of the chemokine superfamily of proinflammatory cytokines . | Northern analysis of mRNA from hypoxic <cell_type>ECs</cell_type> also demonstrated increased levels of <rna>mRNA</rna> for <protein>macrophage chemotactic protein-1</protein> , another member of the <protein>chemokine superfamily</protein> of <protein>proinflammatory cytokines</protein> . |
517 | IL-8 gene induction was associated with the presence of increased binding activity in nuclear extracts from hypoxic ECs for the NF-kB site . | <dna>IL-8 gene</dna> induction was associated with the presence of increased binding activity in nuclear extracts from <cell_type>hypoxic ECs</cell_type> for the NF-kB site . |
518 | Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of IL-8 antigen compared with normoxic controls . | Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of <protein>IL-8 antigen</protein> compared with normoxic controls . |
519 | In mice exposed to hypoxia ( PO2 approximately 30-40 Torr ) , there was increased pulmonary leukostasis , as evidenced by increased myeloperoxidase activity in tissue homogenates . | In mice exposed to hypoxia ( PO2 approximately 30-40 Torr ) , there was increased pulmonary leukostasis , as evidenced by increased <protein>myeloperoxidase</protein> activity in tissue homogenates . |
520 | In parallel , increased levels of transcripts for IP-10 , a murine homologue in the chemokine family related to IL-8 , were observed in hypoxic lung tissue . | In parallel , increased levels of transcripts for <protein>IP-10</protein> , a murine homologue in the <protein>chemokine family</protein> related to <protein>IL-8</protein> , were observed in hypoxic lung tissue . |
521 | Taken together , these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis . | Taken together , these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis . |
522 | Thrombin and thrombin receptor agonist peptide induce early events of T cell activation and synergize with TCR cross-linking for CD69 expression and interleukin 2 production . | <protein>Thrombin</protein> and <protein>thrombin receptor</protein> agonist peptide induce early events of T cell activation and synergize with <protein>TCR</protein> cross-linking for <protein>CD69</protein> expression and interleukin 2 production . |
523 | Thrombin stimulation of the T leukemic cell line Jurkat induced a transient increase in [ Ca2+ ] i . | <protein>Thrombin</protein> stimulation of the <cell_line>T leukemic cell line Jurkat</cell_line> induced a transient increase in [ Ca2+ ] i . |
524 | Proteolytic activity of the enzyme was required for this effect since diisopropyl fluorophosphate-thrombin failed to increase [ Ca2+ ] i . | Proteolytic activity of the <protein>enzyme</protein> was required for this effect since <protein>diisopropyl fluorophosphate-thrombin</protein> failed to increase [ Ca2+ ] i . |
525 | Furthermore , hirudin and anti-thrombin III inhibited the thrombin-induced [ Ca2+ ] i rise in Jurkat T cells . | Furthermore , hirudin and <protein>anti-thrombin III</protein> inhibited the thrombin-induced [ Ca2+ ] i rise in <cell_line>Jurkat T cells</cell_line> . |
526 | A synthetic thrombin receptor agonist peptide ( TRP ) of 7 residues ( SFLLRNP ) was found to be as effective as thrombin for [ Ca2+ ] i mobilization , and both agonists induced Ca2+ release exclusively from internal stores . | A synthetic <protein>thrombin receptor</protein> agonist peptide ( TRP ) of 7 residues ( SFLLRNP ) was found to be as effective as <protein>thrombin</protein> for [ Ca2+ ] i mobilization , and both agonists induced Ca2+ release exclusively from internal stores . |
527 | Thrombin stimulated tyrosine phosphorylation of several proteins of molecular mass 40 , 42 , 70 , 120 , and 130 kDa . | <protein>Thrombin</protein> stimulated tyrosine phosphorylation of several proteins of <protein>molecular mass 40 , 42 , 70 , 120 , and 130 kDa</protein> . |
528 | There was a good correlation between thrombin -induced tyrosine phosphorylation of the latter three proteins and Ca2+ mobilization . | There was a good correlation between <protein>thrombin</protein> -induced tyrosine phosphorylation of the latter three proteins and Ca2+ mobilization . |
529 | Thrombin and TRP also caused translocation of protein kinase C from the cytosol to the plasma membrane . | <protein>Thrombin</protein> and TRP also caused translocation of <protein>protein kinase C</protein> from the cytosol to the plasma membrane . |
530 | As a likely consequence of these events , thrombin activated the nuclear factor NF-kB . | As a likely consequence of these events , <protein>thrombin</protein> activated the <protein>nuclear factor NF-kB</protein> . |
531 | Several cell lines of hematopoietic origin including the leukemic T cell line HPB.ALL and the erythroleukemic cell line K562 were responsive to thrombin , whereas others such as THP1 , a myelomonocytic cell line , and BL2 , a Burkitt lymphoma were refractory to thrombin or TRP stimulation . | Several cell lines of hematopoietic origin including the <cell_line>leukemic T cell line HPB.ALL</cell_line> and the <cell_line>erythroleukemic cell line K562</cell_line> were responsive to <protein>thrombin</protein> , whereas others such as <cell_line>THP1</cell_line> , a <cell_line>myelomonocytic cell line</cell_line> , and <cell_line>BL2 ,</cell_line> a <cell_line>Burkitt lymphoma</cell_line> were refractory to <protein>thrombin</protein> or TRP stimulation . |
532 | The magnitude of the thrombin response in the different cell types paralleled the expression of the thrombin receptor mRNA . | The magnitude of the <protein>thrombin</protein> response in the different cell types paralleled the expression of the <rna>thrombin receptor mRNA</rna> . |
533 | We found that activation of Jurkat T cells by a combination of phytohemagglutinin and phorbol 12-myristate 13-acetate led to a dramatic inhibition of thrombin receptor mRNA expression and to a concomitant loss of the thrombin response . | We found that activation of <cell_line>Jurkat T cells</cell_line> by a combination of <protein>phytohemagglutinin</protein> and phorbol 12-myristate 13-acetate led to a dramatic inhibition of <rna>thrombin receptor mRNA</rna> expression and to a concomitant loss of the <protein>thrombin</protein> response . |
534 | Finally , we demonstrate that thrombin and TRP enhanced CD69 expression and interleukin 2 production induced by T cell receptor cross-linking in both Jurkat T cells and peripheral blood lymphocytes . | Finally , we demonstrate that <protein>thrombin</protein> and TRP enhanced <protein>CD69</protein> expression and <protein>interleukin 2</protein> production induced by <protein>T cell receptor</protein> cross-linking in both <cell_line>Jurkat T cells</cell_line> and peripheral blood <cell_type>lymphocytes</cell_type> . |
535 | These findings highlight the role of thrombin as a potential regulator of T lymphocyte activation . | These findings highlight the role of <protein>thrombin</protein> as a potential regulator of <cell_type>T lymphocyte</cell_type> activation . |
536 | Stress response of senescent T lymphocytes : reduced hsp70 is independent of the proliferative block . | Stress response of <cell_type>senescent T lymphocytes</cell_type> : reduced <protein>hsp70</protein> is independent of the proliferative block . |
537 | Senescent human T lymphocyte cultures are unable to undergo proliferation , but show no difference from early passage cells in cytotoxic function or surface antigenic profile . | <cell_line>Senescent human T lymphocyte cultures</cell_line> are unable to undergo proliferation , but show no difference from <cell_line>early passage cells</cell_line> in cytotoxic function or surface antigenic profile . |
538 | A second feature of senescent T cells is the dramatic reduction in hsp70 production in response to heat shock . | A second feature of <cell_line>senescent T cells</cell_line> is the dramatic reduction in <protein>hsp70</protein> production in response to heat shock . |
539 | This decline is associated with a decrease in binding of nuclear extracts to the consensus heat shock element . | This decline is associated with a decrease in binding of nuclear extracts to the <dna>consensus heat shock element</dna> . |
540 | Interestingly , the progressive decline in the heat shock response of cultured T cells correlates with the percent proliferative life span completed rather than with the actual proliferative activity at the time of heat shock . | Interestingly , the progressive decline in the heat shock response of <cell_line>cultured T cells</cell_line> correlates with the percent proliferative life span completed rather than with the actual proliferative activity at the time of heat shock . |
541 | This suggests that for senescent T cells the reduced ability to respond to heat shock by producing hsp70 , although possibly lying at the level of transcriptional control , may nevertheless be unrelated to the reduced DNA synthesis or the diminished proliferative activity also manifested by these cells . | This suggests that for <cell_type>senescent T cells</cell_type> the reduced ability to respond to heat shock by producing <protein>hsp70</protein> , although possibly lying at the level of transcriptional control , may nevertheless be unrelated to the reduced DNA synthesis or the diminished proliferative activity also manifested by these cells . |
542 | Involvement of phospholipase D in the activation of transcription factor AP-1 in human T lymphoid Jurkat cells . | Involvement of <protein>phospholipase D</protein> in the activation of <protein>transcription factor AP-1</protein> in <cell_line>human T lymphoid Jurkat cells</cell_line> . |
543 | The induction of the AP-1 transcription factor has been ascribed to the early events leading to T lymphocyte activation . | The induction of the <protein>AP-1</protein> <protein>transcription factor</protein> has been ascribed to the early events leading to T lymphocyte activation . |
544 | We have examined the possibility that stimulation of phospholipase D ( PLD ) may regulate activation of transcription factor AP-1 in human T cells by transfecting human T lymphocyte Jurkat cells with a plasmid containing an AP-1 enhancer element and a chloramphenicol acetyltransferase reporter gene . | We have examined the possibility that stimulation of <protein>phospholipase D</protein> ( <protein>PLD</protein> ) may regulate activation of <protein>transcription factor AP-1</protein> in human T cells by transfecting human <cell_line>T lymphocyte Jurkat cells</cell_line> with a plasmid containing an <dna>AP-1 enhancer element</dna> and a <dna>chloramphenicol acetyltransferase reporter gene</dna> . |
545 | We have detected activatable PLD in Jurkat cells , and we have found that addition of phosphatidic acid ( PA ) , the physiologic product of PLD action on phospholipids , is rapidly incorporated into Jurkat cells and leads to activation of transcription factor AP-1 . | We have detected activatable <protein>PLD</protein> in <cell_line>Jurkat cells</cell_line> , and we have found that addition of phosphatidic acid ( PA ) , the physiologic product of <protein>PLD</protein> action on phospholipids , is rapidly incorporated into <cell_line>Jurkat cells</cell_line> and leads to activation of <protein>transcription factor AP-1</protein> . |
546 | Treatment of Jurkat cells with anti-CD3 mAb activated both PLD and transcription factor AP-1 . | Treatment of <cell_line>Jurkat cells</cell_line> with <protein>anti-CD3 mAb</protein> activated both <protein>PLD</protein> and <protein>transcription factor AP-1</protein> . |
547 | Wortmannin , an inhibitor of receptor-coupled PLD activation , blocked the anti-CD3 -induced increases in both PLD activity and AP-1 enhancer activity . | Wortmannin , an inhibitor of receptor-coupled <protein>PLD</protein> activation , blocked the <protein>anti-CD3</protein> -induced increases in both <protein>PLD</protein> activity and <dna>AP-1 enhancer</dna> activity . |
548 | We found a good correlation in the transfected cells between PLD activation and induction of AP-1 enhancer activity under different experimental conditions . | We found a good correlation in the <cell_line>transfected cells</cell_line> between <protein>PLD</protein> activation and induction of <dna>AP-1 enhancer</dna> activity under different experimental conditions . |
549 | Furthermore , ethanol , an inhibitor of the PLD pathway , blocked the anti-CD3-stimulated AP-1 enhancer activity . | Furthermore , ethanol , an inhibitor of the <protein>PLD</protein> pathway , blocked the anti-CD3-stimulated <dna>AP-1 enhancer</dna> activity . |
550 | However , this anti-CD3 -mediated response was not inhibited by neomycin , an inhibitor of phosphoinositide hydrolysis . | However , this <protein>anti-CD3</protein> -mediated response was not inhibited by neomycin , an inhibitor of phosphoinositide hydrolysis . |
551 | The increases in AP-1 enhancer activity induced by PA or anti-CD3 mAb were efficiently abrogated by the presence of propranolol , an inhibitor of PA phosphohydrolase and protein kinase C ( PKC ) . | The increases in <dna>AP-1 enhancer</dna> activity induced by PA or <protein>anti-CD3 mAb</protein> were efficiently abrogated by the presence of propranolol , an inhibitor of PA <protein>phosphohydrolase</protein> and <protein>protein kinase C</protein> ( <protein>PKC</protein> ) . |
552 | Furthermore , the PA -and the anti-CD3 -induced increases in AP-1 enhancer activity were blocked by the presence of PKC inhibitors or by PKC down-regulation . | Furthermore , the PA -and the <protein>anti-CD3</protein> -induced increases in <dna>AP-1 enhancer</dna> activity were blocked by the presence of <protein>PKC</protein> inhibitors or by <protein>PKC</protein> down-regulation . |
553 | These data indicate that PLD stimulation can activate the transcription factor AP-1 in T lymphocytes , and suggest that the induction of AP-1 enhancer factor activity by PA is mediated via PKC stimulation , either through a direct activating effect of PA or through PA-derived diacylglycerol formation . | These data indicate that <protein>PLD</protein> stimulation can activate the <protein>transcription factor AP-1</protein> in <cell_type>T lymphocytes</cell_type> , and suggest that the induction of <dna>AP-1 enhancer</dna> factor activity by PA is mediated via <protein>PKC</protein> stimulation , either through a direct activating effect of PA or through PA-derived diacylglycerol formation . |
554 | These data also provide evidence for a role of PLD -derived lipids in the induction of AP-1 enhancer activity resulting from stimulation of the TCR/CD3 complex , suggesting that increased PLD activity can play an important role in T lymphocyte activation . | These data also provide evidence for a role of <protein>PLD</protein> -derived lipids in the induction of <dna>AP-1 enhancer</dna> activity resulting from stimulation of the <protein>TCR/CD3 complex</protein> , suggesting that increased <protein>PLD</protein> activity can play an important role in <cell_type>T lymphocyte</cell_type> activation . |
555 | Upregulation of bcl-2 by the Epstein-Barr virus latent membrane protein LMP1 : a B-cell-specific response that is delayed relative to NF-kappa B activation and to induction of cell surface markers . | Upregulation of <dna>bcl-2</dna> by the <protein>Epstein-Barr virus latent membrane protein</protein> <protein>LMP1</protein> : a B-cell-specific response that is delayed relative to <protein>NF-kappa B</protein> activation and to induction of <protein>cell surface markers</protein> . |
556 | An ability of the Epstein-Barr virus latent membrane protein LMP1 to enhance the survival of infected B cells through upregulation of the bcl-2 oncogene was first suggested by experiments involving gene transfection and the selection of stable LMP1+ clones ( S.Henderson , M. Rowe , C.Gregory , F.Wang , E.Kieff , and A.Rickinson , Cell 65 : 1107-1115 , 1991 ) . | An ability of the <protein>Epstein-Barr virus latent membrane protein</protein> <protein>LMP1</protein> to enhance the survival of <cell_type>infected B cells</cell_type> through upregulation of the <dna>bcl-2 oncogene</dna> was first suggested by experiments involving gene transfection and the selection of stable <cell_line>LMP1+ clones</cell_line> ( S.Henderson , M. Rowe , C.Gregory , F.Wang , E.Kieff , and A.Rickinson , Cell 65 : 1107-1115 , 1991 ) . |
557 | However , it was not possible to ascertain whether Bcl-2 upregulation was a specific consequence of LMP1 expression or an artifact of the selection procedure whereby rare Bcl-2+ cells already present in the starting population might best be able to tolerate the potentially toxic effects of LMP1 . | However , it was not possible to ascertain whether <protein>Bcl-2</protein> upregulation was a specific consequence of <protein>LMP1</protein> expression or an artifact of the selection procedure whereby rare <cell_line>Bcl-2+ cells</cell_line> already present in the starting population might best be able to tolerate the potentially toxic effects of <protein>LMP1</protein> . |
558 | We therefore reexamined this issue by using two different experimental approaches that allowed LMP1 -induced effects to be monitored immediately following expression of the viral protein and in the absence of selective pressures ; activation of the NF-kappa B transcription factor and upregulation of the cell adhesion molecule ICAM-1 were used as early indices of LMP1 function . | We therefore reexamined this issue by using two different experimental approaches that allowed <protein>LMP1</protein> -induced effects to be monitored immediately following expression of the viral protein and in the absence of selective pressures ; activation of the <protein>NF-kappa B</protein> <protein>transcription factor</protein> and upregulation of the <protein>cell adhesion molecule</protein> <protein>ICAM-1</protein> were used as early indices of <protein>LMP1</protein> function . |
559 | In the first approach , stable clones of two B-cell lines carrying an LMP1 gene under the control of an inducible metallothionein promoter were induced to express LMP1 in all cells . | In the first approach , stable clones of two <cell_line>B-cell lines</cell_line> carrying an <protein>LMP1</protein> gene under the control of an inducible <dna>metallothionein promoter</dna> were induced to express <protein>LMP1</protein> in all cells . |
560 | Activation of NK-kappa B and upregulation of ICAM-1 occurred within 24 h and were followed at 48 to 72 h by upregulation of Bcl-2 . | Activation of <protein>NK-kappa B</protein> and upregulation of <protein>ICAM-1</protein> occurred within 24 h and were followed at 48 to 72 h by upregulation of <protein>Bcl-2</protein> . |
561 | In the second approach , we tested the generality of this phenomenon by transiently expressing LMP1 from a strong constitutively active promoter in a range of different cell types . | In the second approach , we tested the generality of this phenomenon by transiently expressing <protein>LMP1</protein> from a strong constitutively active promoter in a range of different cell types . |
562 | All six B-cell lines tested showed NF-kappa B activation in response to LMP1 expression , and this was followed in five of six lines by expression of ICAM-1 and Bcl-2 . | All six <cell_line>B-cell lines</cell_line> tested showed <protein>NF-kappa B</protein> activation in response to <protein>LMP1</protein> expression , and this was followed in five of six lines by expression of <protein>ICAM-1</protein> and <protein>Bcl-2</protein> . |
563 | In the same experiments , all three non- B-cell lines showed NF-kappa B activation and ICAM-1 upregulation but never any effect upon Bcl-2 . | In the same experiments , all three non- <cell_line>B-cell lines</cell_line> showed <protein>NF-kappa B</protein> activation and <protein>ICAM-1</protein> upregulation but never any effect upon <protein>Bcl-2</protein> . |
564 | We therefore conclude that Bcl-2 upregulation is part of the panoply of cellular changes induced by LMP1 but that the effect is cell type specific . | We therefore conclude that <protein>Bcl-2</protein> upregulation is part of the panoply of cellular changes induced by <protein>LMP1</protein> but that the effect is cell type specific . |
565 | Our data also suggest that whilst NF-kappa B may be an essential component of LMP1 signal transduction , other cell-specific factors may be required to effect some functions of the viral protein . | Our data also suggest that whilst <protein>NF-kappa B</protein> may be an essential component of <protein>LMP1</protein> signal transduction , other <protein>cell-specific factors</protein> may be required to effect some functions of the <protein>viral protein</protein> . |
566 | Long-term inositol phosphate release , but not tyrosine kinase activity , correlates with IL-2 secretion and NF-AT induction in anti-CD3-activated peripheral human T lymphocytes . | Long-term inositol phosphate release , but not <protein>tyrosine kinase</protein> activity , correlates with <protein>IL-2</protein> secretion and <protein>NF-AT</protein> induction in <cell_line>anti-CD3-activated peripheral human T lymphocytes</cell_line> . |
567 | The cascade of events within the first few minutes of T cell stimulation has been well characterized . | The cascade of events within the first few minutes of <cell_type>T cell</cell_type> stimulation has been well characterized . |
568 | Although many second messengers have been shown to be necessary and sufficient for T cell activation in a number of model systems , the rate-limiting step in peripheral T cells has not been demonstrated . | Although many second messengers have been shown to be necessary and sufficient for <cell_type>T cell</cell_type> activation in a number of model systems , the rate-limiting step in <cell_type>peripheral T cells</cell_type> has not been demonstrated . |
569 | To model effective versus ineffective CD3 -mediated stimulation in peripheral T cells , we used two anti-CD3 mAbs that differ in their ability to stimulate purified T cells : OKT3 , which causes early second messenger generation but is unable to activate T cells without a second signal , and 64.1 , which stimulates T cell proliferation on its own . | To model effective versus ineffective <protein>CD3</protein> -mediated stimulation in <cell_type>peripheral T cells</cell_type> , we used two <protein>anti-CD3 mAbs</protein> that differ in their ability to stimulate <cell_type>purified T cells</cell_type> : <protein>OKT3</protein> , which causes early second messenger generation but is unable to activate <cell_type>T cells</cell_type> without a second signal , and <protein>64.1</protein> , which stimulates <cell_type>T cell</cell_type> proliferation on its own . |
570 | We found that tyrosine kinase activity was similar for both mAbs over a period of hours . | We found that <protein>tyrosine kinase</protein> activity was similar for both <protein>mAbs</protein> over a period of hours . |
571 | However , the inositol phosphate response was stronger for 64.1 than for OKT3 . | However , the inositol phosphate response was stronger for <protein>64.1</protein> than for <protein>OKT3</protein> . |
572 | To tie these events to gene activation , we measured NF-kappa B and NF-AT activity in the nucleus after anti-CD3 stimulation . | To tie these events to gene activation , we measured <protein>NF-kappa B</protein> and <protein>NF-AT</protein> activity in the nucleus after <protein>anti-CD3</protein> stimulation . |
573 | Both stimuli induced the appearance of the NF-kappa B components ( c-Rel , p65 ( RelA ) , and p50 ( NF-kappa B1 ) ) and NF-kappa B DNA binding activity in the nucleus . | Both stimuli induced the appearance of the <protein>NF-kappa B components</protein> ( <protein>c-Rel</protein> , <protein>p65</protein> ( <protein>RelA</protein> ) , and <protein>p50</protein> ( <protein>NF-kappa B1</protein> ) ) and <protein>NF-kappa B</protein> DNA binding activity in the nucleus . |
574 | However , only 64.1 induced NF-AT in the nucleus , correlating with its ability to activate T cells . | However , only <protein>64.1</protein> induced <protein>NF-AT</protein> in the nucleus , correlating with its ability to activate <cell_type>T cells</cell_type> . |
575 | Thus , NF-AT induction and IL-2 secretion were correlated with the levels of inositol phosphate release but not with gross levels of tyrosine kinase activity induced late following the response . | Thus , <protein>NF-AT</protein> induction and <protein>IL-2</protein> secretion were correlated with the levels of inositol phosphate release but not with gross levels of <protein>tyrosine kinase</protein> activity induced late following the response . |
576 | On the other hand , NF-kappa B induction and IL-2 receptor expression occurred even with the smaller second messenger response generated by OKT3 . | On the other hand , <protein>NF-kappa B</protein> induction and <protein>IL-2</protein> receptor expression occurred even with the smaller second messenger response generated by <protein>OKT3</protein> . |
577 | HLA-DR- , CD33+ , CD56+ , CD16- myeloid/natural killer cell acute leukemia : a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3 [ see comments ] | HLA-DR- , CD33+ , CD56+ , CD16- myeloid/natural killer cell acute leukemia : a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3 [ see comments ] |
578 | We have identified and characterized a previously unrecognized form of acute leukemia that shares features of both myeloid and natural killer ( NK ) cells . | We have identified and characterized a previously unrecognized form of acute leukemia that shares features of both <cell_type>myeloid and natural killer ( NK ) cells</cell_type> . |
579 | From a consecutive series of 350 cases of adult de novo acute myeloid leukemia ( AML ) , we identified 20 cases ( 6 % ) with a unique immunophenotype : CD33+ , CD56+ , CD11a+ , CD13lo , CD15lo , CD34+/- , HLA-DR - , CD16 - . | From a consecutive series of 350 cases of adult de novo acute myeloid leukemia ( AML ) , we identified 20 cases ( 6 % ) with a unique immunophenotype : CD33+ , CD56+ , CD11a+ , CD13lo , CD15lo , CD34+/- , <protein>HLA-DR</protein> - , <protein>CD16</protein> - . |
580 | Multicolor flow cytometric assays confirmed the coexpression of myeloid ( CD33 , CD13 , CD15 ) and NK cell-associated ( CD56 ) antigens in each case , whereas reverse transcription polymerase chain reaction ( RT-PCR ) assays confirmed the identity of CD56 ( neural cell adhesion molecule ) in leukemic blasts . | Multicolor flow cytometric assays confirmed the coexpression of <protein>myeloid ( CD33 , CD13 , CD15 ) and NK cell-associated ( CD56 ) antigens</protein> in each case , whereas reverse transcription polymerase chain reaction ( RT-PCR ) assays confirmed the identity of <protein>CD56</protein> ( <protein>neural cell adhesion molecule</protein> ) in <cell_type>leukemic blasts</cell_type> . |
581 | Although two cases expressed CD4 , no case expressed CD2 , CD3 , or CD8 and no case showed clonal rearrangement of genes encoding the T-cell receptor ( TCR beta , gamma , delta ) . | Although two cases expressed <protein>CD4</protein> , no case expressed <protein>CD2</protein> , <protein>CD3</protein> , or <protein>CD8</protein> and no case showed clonal rearrangement of genes encoding the <protein>T-cell receptor</protein> ( <protein>TCR beta , gamma , delta</protein> ) . |
582 | Leukemic blasts in the majority of cases shared unique morphologic features ( deeply invaginated nuclear membranes , scant cytoplasm with fine azurophilic granularity , and finely granular Sudan black B and myeloperoxidase cytochemical reactivity ) that were remarkably similar to those of acute promyelocytic leukemia ( APL ) ; particularly the microgranular variant ( FAB AML-M3v ) . | Leukemic blasts in the majority of cases shared unique morphologic features ( deeply invaginated nuclear membranes , scant cytoplasm with fine azurophilic granularity , and finely granular Sudan black B and <protein>myeloperoxidase</protein> cytochemical reactivity ) that were remarkably similar to those of acute promyelocytic leukemia ( APL ) ; particularly the <protein>microgranular variant</protein> ( <protein>FAB AML-M3v</protein> ) . |
583 | However , all 20 cases lacked the t ( 15 ; 17 ) and 17 cases tested lacked the promyelocytic/retinoic acid receptor alpha ( RAR alpha ) fusion transcript in RT-PCR assays ; 12 cases had 46 , XX or 46 , XY karyotypes , whereas 2 cases had abnormalities of chromosome 17q : 1 with del ( 17 ) ( q25 ) and the other with t ( 11 ; 17 ) ( q23 ; q21 ) and the promyelocytic leukemia zinc finger/RAR alpha fusion transcript . | However , all 20 cases lacked the t ( 15 ; 17 ) and 17 cases tested lacked the <rna>promyelocytic/retinoic acid receptor alpha ( RAR alpha ) fusion transcript</rna> in RT-PCR assays ; 12 cases had 46 , XX or 46 , XY karyotypes , whereas 2 cases had abnormalities of <dna>chromosome 17q</dna> : 1 with <dna>del ( 17 ) ( q25 )</dna> and the other with <dna>t ( 11 ; 17 ) ( q23 ; q21 )</dna> and the <rna>promyelocytic leukemia zinc finger/RAR alpha fusion transcript</rna> . |
584 | All cases tested ( 6/20 ) , including the case with t ( 11 ; 17 ) , failed to differentiate in vitro in response to all-trans retinoic acid ( ATRA ) , suggesting that these cases may account for some APLs that have not shown a clinical response to ATRA . | All cases tested ( 6/20 ) , including the case with <dna>t ( 11 ; 17 )</dna> , failed to differentiate in vitro in response to all-trans retinoic acid ( ATRA ) , suggesting that these cases may account for some APLs that have not shown a clinical response to ATRA . |
585 | Four of 6 cases tested showed functional NK cell-mediated cytotoxicity , suggesting a relationship between these unique CD33+ , CD56+ , CD16 -acute leukemias and normal CD56+ , CD16- NK precursor cells . | Four of 6 cases tested showed functional NK cell-mediated cytotoxicity , suggesting a relationship between these unique CD33+ , CD56+ , <protein>CD16</protein> -acute leukemias and <cell_type>normal CD56+ , CD16- NK precursor cells</cell_type> . |
586 | Using a combination of panning and multiparameter flow cytometric sorting , we identified a normal CD56+ , CD33+ , CD16- counterpart cell at a frequency of 1 % to 2 % in the peripheral blood of healthy individuals . | Using a combination of panning and multiparameter flow cytometric sorting , we identified a <cell_type>normal CD56+ , CD33+ , CD16- counterpart cell</cell_type> at a frequency of 1 % to 2 % in the peripheral blood of healthy individuals . |
587 | Our studies suggest that this form of acute leukemia may arise from transformation of a precursor cell common to both the myeloid and NK cell lineages ; thus we propose the designation myeloid/NK acute leukemia . | Our studies suggest that this form of acute leukemia may arise from transformation of a precursor cell common to both the <cell_type>myeloid and NK cell lineages</cell_type> ; thus we propose the designation myeloid/NK acute leukemia . |
588 | Recognition of this new leukemic entity will be important in distinguishing these ATRA-nonresponsive cases from ATRA-responsive true APL . | Recognition of this new leukemic entity will be important in distinguishing these ATRA-nonresponsive cases from ATRA-responsive true APL . |
589 | IL-4 down-regulates IL-2 - , IL-3 - , and GM-CSF -induced cytokine gene expression in peripheral blood monocytes . | <protein>IL-4</protein> down-regulates <protein>IL-2</protein> - , <protein>IL-3</protein> - , and <protein>GM-CSF</protein> -induced cytokine gene expression in peripheral blood monocytes . |
590 | IL-4 , a product of the T-helper 0 ( Th0 ) and 2 ( Th2 ) subset , was originally described as a B-cell stimulatory factor and has subsequently been found to suppress IL-1 alpha , IL-1 beta , IL-6 , IL-8 , and TNF-alpha gene expression in monocytes stimulated with LPS , and to upregulate IL-1 receptor antagonist ( IL1-RA ) gene expression . | <protein>IL-4</protein> , a product of the <cell_type>T-helper 0 ( Th0 ) and 2 ( Th2 ) subset</cell_type> , was originally described as a <protein>B-cell stimulatory factor</protein> and has subsequently been found to suppress IL-1 alpha , IL-1 beta , IL-6 , IL-8 , and TNF-alpha gene expression in <cell_type>monocytes</cell_type> stimulated with LPS , and to upregulate <dna>IL-1 receptor antagonist ( IL1-RA ) gene</dna> expression . |
591 | In this study we investigated the effect of IL-4 on the expression of cytokine genes in monocytes evoked by other T-helper cell cytokines : IL-2 , IL-3 , and GM-CSF . | In this study we investigated the effect of <protein>IL-4</protein> on the expression of <dna>cytokine genes</dna> in <cell_type>monocytes</cell_type> evoked by other <protein>T-helper cell cytokines</protein> : <protein>IL-2</protein> , <protein>IL-3</protein> , and <protein>GM-CSF</protein> . |
592 | IL-4 down-regulated mRNA accumulation of the proinflammatory cytokines IL-1 beta , IL-8 , and TNF-alpha in monocytes stimulated with IL-2 , IL-3 , and GM-CSF . | <protein>IL-4</protein> down-regulated mRNA accumulation of the <protein>proinflammatory cytokines</protein> <protein>IL-1 beta</protein> , <protein>IL-8</protein> , and <protein>TNF-alpha</protein> in <cell_type>monocytes</cell_type> stimulated with <protein>IL-2</protein> , <protein>IL-3</protein> , and <protein>GM-CSF</protein> . |
593 | IL-4 also suppressed the IL-2 -induced IL-6 mRNA expression . | <protein>IL-4</protein> also suppressed the <protein>IL-2</protein> -induced <protein>IL-6</protein> mRNA expression . |
594 | Temporal analysis of the IL-4 down-regulatory effect on the IL-2- , IL-3- , or GM-CSF-induced proinflammatory cytokine gene expression in monocytes provided evidence that IL-4 acts predominantly on the post-transcriptional level . | Temporal analysis of the <protein>IL-4</protein> down-regulatory effect on the IL-2- , IL-3- , or GM-CSF-induced proinflammatory cytokine gene expression in <cell_type>monocytes</cell_type> provided evidence that <protein>IL-4</protein> acts predominantly on the post-transcriptional level . |
595 | This was supported by the observation that the down-regulatory capacity of IL-4 appeared to be dependent on de novo protein synthesis . | This was supported by the observation that the down-regulatory capacity of <protein>IL-4</protein> appeared to be dependent on de novo protein synthesis . |
596 | IL-4 did not exert significant influence on the induction of expression of IL-1-RA or various CSFs by IL-2 , IL-3 , and GM-CSF . | <protein>IL-4</protein> did not exert significant influence on the induction of expression of <protein>IL-1-RA</protein> or various <protein>CSFs</protein> by <protein>IL-2</protein> , <protein>IL-3</protein> , and <protein>GM-CSF</protein> . |
597 | ( ABSTRACT TRUNCATED AT 250 WORDS ) | ( ABSTRACT TRUNCATED AT 250 WORDS ) |
598 | Induction of proto-oncogene and cytokine expression in human peripheral blood monocytes and the monocytic cell line THP-1 after stimulation with mycoplasma-derived material MDHM . | Induction of <dna>proto-oncogene</dna> and <protein>cytokine</protein> expression in human peripheral blood <cell_type>monocytes</cell_type> and the <cell_line>monocytic cell line</cell_line> <cell_line>THP-1</cell_line> after stimulation with mycoplasma-derived material MDHM . |
599 | Mycoplasma fermentans-derived high-molecular-weight material ( MDHM ) was originally described to induce differentiation of murine thymocytes to cytolytic effector T-cells by stimulating IL-6 release from adherent cells . | Mycoplasma fermentans-derived high-molecular-weight material ( MDHM ) was originally described to induce differentiation of <cell_type>murine thymocytes</cell_type> to <cell_type>cytolytic effector T-cells</cell_type> by stimulating <protein>IL-6</protein> release from <cell_type>adherent cells</cell_type> . |
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