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 .


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 .


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> .


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 ) .


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> .


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 .


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 .


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> .


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 .


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> .


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> .


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 .


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> .


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> .


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 .


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 .


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 .


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 .


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> .


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 .


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 .


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> .


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 .


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> .


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 ]


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> .


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> - .


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> .


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> ) .


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> ) .


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> .


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 .


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> .


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 .


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 .


Recognition of this new leukemic entity will be important in distinguishing these ATRA-nonresponsive cases from ATRA-responsive true APL .


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 .


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 .


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> .


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> .


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 .


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 .


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 .


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> .


( ABSTRACT TRUNCATED AT 250 WORDS )


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 .


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> .


This study shows that human peripheral blood monocytes ( PBMo ) also respond to MDHM with increases in IL-1 beta , IL-6 and TNF alpha expression , both at the mRNA and protein level .

This study shows that human peripheral blood <cell_type>monocytes</cell_type> ( <cell_type>PBMo</cell_type> ) also respond to MDHM with increases in <protein>IL-1 beta</protein> , <protein>IL-6</protein> and <protein>TNF alpha</protein> expression , both at the mRNA and protein level .


The induced expression of IL-1 beta and TNF alpha mRNA in the monocytic THP-1 cell line increased as quickly as in primary cells .

The induced expression of <rna>IL-1 beta and TNF alpha mRNA</rna> in the monocytic <cell_line>THP-1 cell line</cell_line> increased as quickly as in <cell_type>primary cells</cell_type> .


In contrast to PBMo , THP-1 and 14 other monocytic/myeloid leukemia-derived cell lines did not secrete measurable amounts of the cytokines upon treatment with MDHM .

In contrast to <cell_type>PBMo</cell_type> , <cell_line>THP-1</cell_line> and 14 other <cell_line>monocytic/myeloid leukemia-derived cell lines</cell_line> did not secrete measurable amounts of the <protein>cytokines</protein> upon treatment with MDHM .


IL-1 beta and IL-6 genes contain AP-1 binding sites as regulatory elements , the AP-1 protein being composed of c-jun and c-fos gene products .

<dna>IL-1 beta and IL-6 genes</dna> contain <dna>AP-1 binding sites</dna> as <dna>regulatory elements</dna> , the <protein>AP-1</protein> protein being composed of <protein>c-jun and c-fos gene products</protein> .


In THP-1 cells c-jun mRNA expression increased after incubation with MDHM while positive c-fos expression remained unaffected .

In <cell_line>THP-1 cells</cell_line> <rna>c-jun mRNA</rna> expression increased after incubation with MDHM while positive <dna>c-fos</dna> expression remained unaffected .


Although these data suggest AP-1 regulated cytokine mRNA expression , results from PBMo are not in accordance with this notion .

Although these data suggest <protein>AP-1</protein> regulated <protein>cytokine</protein> mRNA expression , results from <cell_type>PBMo</cell_type> are not in accordance with this notion .


In the primary cells MDHM-induced elevation of cytokine mRNA levels was preceded by a downregulation of c-fos expression while positive c-jun expression was not modulated .

In the <cell_type>primary cells</cell_type> MDHM-induced elevation of <rna>cytokine mRNA</rna> levels was preceded by a downregulation of <dna>c-fos</dna> expression while positive <dna>c-jun</dna> expression was not modulated .


c-myc mRNA expression , constitutively high in THP-1 cells , was induced in MDHM-stimulated PBMo .

<rna>c-myc mRNA</rna> expression , constitutively high in <cell_line>THP-1 cells</cell_line> , was induced in MDHM-stimulated <cell_type>PBMo</cell_type> .


In conclusion , MDHM-stimulated induction of cytokine mRNA expression was accompanied by different proto-oncogene responses in PBMo and THP-1 cells .

In conclusion , MDHM-stimulated induction of <rna>cytokine mRNA</rna> expression was accompanied by different <dna>proto-oncogene</dna> responses in <cell_type>PBMo</cell_type> and <cell_line>THP-1 cells</cell_line> .


These differences may represent different regulatory pathways of the two cell systems .


Alternatively , these data support the notion that neither AP-1 nor the c-myc protein are involved in the MDHM-induced increase in IL-1 beta , IL-6 or TNF alpha mRNA levels .

Alternatively , these data support the notion that neither <protein>AP-1</protein> nor the <protein>c-myc protein</protein> are involved in the MDHM-induced increase in IL-1 beta , IL-6 or TNF alpha mRNA levels .


Furthermore , the present results demonstrate clearly that mycoplasma products can have a profound impact on the activation status of eukaryotic cells .

Furthermore , the present results demonstrate clearly that <protein>mycoplasma products</protein> can have a profound impact on the activation status of <cell_type>eukaryotic cells</cell_type> .


Novel membrane receptors for aldosterone in human lymphocytes : a 50 kDa protein on SDS-PAGE .

<protein>Novel membrane receptors</protein> for aldosterone in <cell_type>human lymphocytes</cell_type> : a <protein>50 kDa protein</protein> on SDS-PAGE .


Fast in vitro effects of aldosterone on the Na+/H ( + ) -exchanger , inositoltrisphosphate generation and corresponding specific binding to plasma membranes at Kd-values of approximately 0.1 nM have been found in human mononuclear leukocytes and vascular smooth muscle cells .

Fast in vitro effects of aldosterone on the <protein>Na+/H ( + ) -exchanger</protein> , inositoltrisphosphate generation and corresponding specific binding to plasma membranes at Kd-values of approximately 0.1 nM have been found in <cell_type>human mononuclear leukocytes</cell_type> and <cell_type>vascular smooth muscle cells</cell_type> .


The novel aldosterone membrane receptor was analyzed on SDS-PAGE after labeling of microsomal membranes from human mononuclear leukocytes with a [ 125I ] -aldosterone-derivative by use of BASED as a photoactivatable crosslinker .

The novel aldosterone membrane receptor was analyzed on SDS-PAGE after labeling of microsomal membranes from <cell_type>human mononuclear leukocytes</cell_type> with a [ 125I ] -aldosterone-derivative by use of BASED as a photoactivatable crosslinker .


Binding of 1 nM [ 125I ] -aldosterone was found at a molecular weight of approximately 50 kDa which was absent with 1 microM cold aldosterone , but not cortisol in the binding media .


This aldosterone-selectivity is typical and discriminatory for the new aldosterone membrane receptor .

This aldosterone-selectivity is typical and discriminatory for the new <protein>aldosterone membrane receptor</protein> .


Solubilization of the receptor protein from membranes by high salt concentrations ( 1 M NaCl , 1 mM EDTA ) was not achieved .

Solubilization of the <protein>receptor protein</protein> from membranes by high salt concentrations ( 1 M NaCl , 1 mM EDTA ) was not achieved .


It , thus , appears as an integral membrane protein .

It , thus , appears as an <protein>integral membrane protein</protein> .


Dithiothreitol , a sulfhydryl agent , does not reduce specific aldosterone binding indicating the absence of SH-groups in the binding domain or sensitive structures of the receptors .

Dithiothreitol , a sulfhydryl agent , does not reduce specific aldosterone binding indicating the absence of <protein>SH-groups</protein> in the <protein>binding domain</protein> or sensitive structures of the receptors .


The results are the first to characterize the novel membrane receptor for aldosterone with regard to molecular weight and basic properties .

The results are the first to characterize the <protein>novel membrane receptor</protein> for aldosterone with regard to molecular weight and basic properties .


These findings and other related results are reviewed here .


A transcriptional regulatory element is associated with a nuclease-hypersensitive site in the pol gene of human immunodeficiency virus type 1 .

A <dna>transcriptional regulatory element</dna> is associated with a <dna>nuclease-hypersensitive site</dna> in the <dna>pol gene</dna> of human immunodeficiency virus type 1 .


Analysis of the chromatin organization of the integrated human immunodeficiency virus type 1 ( HIV-1 ) genome has previously revealed a major constitutive DNase I-hypersensitive site associated with the pol gene ( E. Verdin , J. Virol. 65 : 6790-6799 , 1991 ) .

Analysis of the chromatin organization of the integrated <dna>human immunodeficiency virus type 1 ( HIV-1 ) genome</dna> has previously revealed a <dna>major constitutive DNase I-hypersensitive site</dna> associated with the <dna>pol gene</dna> ( E. Verdin , J. Virol. 65 : 6790-6799 , 1991 ) .


In the present report , high-resolution mapping of this site with DNase I and micrococcal nuclease identified a nucleosome-free region centered around nucleotides ( nt ) 4490 to 4766 .

In the present report , high-resolution mapping of this site with <protein>DNase I</protein> and <protein>micrococcal nuclease</protein> identified a <dna>nucleosome-free region</dna> centered around <dna>nucleotides ( nt ) 4490 to 4766</dna> .


A 500-bp fragment encompassing this hypersensitive site ( nt 4481 to 4982 ) exhibited transcription-enhancing activity ( two- to threefold ) when it was cloned in its natural position with respect to the HIV-1 promoter after transient transfection in U937 and CEM cells .

A <dna>500-bp fragment</dna> encompassing this <dna>hypersensitive site</dna> ( <dna>nt 4481 to 4982</dna> ) exhibited transcription-enhancing activity ( two- to threefold ) when it was cloned in its natural position with respect to the <dna>HIV-1 promoter</dna> after transient transfection in <cell_line>U937</cell_line> and <cell_line>CEM cells</cell_line> .


Using in vitro footprinting and gel shift assays , we have identified four distinct binding sites for nuclear proteins within this positive regulatory element .

Using in vitro footprinting and gel shift assays , we have identified four distinct <dna>binding sites</dna> for <protein>nuclear proteins</protein> within this <dna>positive regulatory element</dna> .


Site B ( nt 4519 to 4545 ) specifically bound four distinct nuclear protein complexes : a ubiquitous factor , a T-cell-specific factor , a B-cell-specific factor , and the monocyte/macrophage- and B-cell-specific transcription factor PU.1/Spi-1 .

<dna>Site B</dna> ( <dna>nt 4519 to 4545</dna> ) specifically bound four distinct <protein>nuclear protein complexes</protein> : a <protein>ubiquitous factor</protein> , a <protein>T-cell-specific factor</protein> , a <protein>B-cell-specific factor</protein> , and the <protein>monocyte/macrophage- and B-cell-specific transcription factor</protein> <protein>PU.1/Spi-1</protein> .


In most HIV-1 isolates in which this PU box was not conserved , it was replaced by a binding site for the related factor Ets1 .

In most HIV-1 isolates in which this <dna>PU box</dna> was not conserved , it was replaced by a <dna>binding site</dna> for the related factor <protein>Ets1</protein> .


Factors binding to site C ( nt 4681 to 4701 ) had a DNA-binding specificity similar to that of factors binding to site B , except for PU.1/Spi-1 .

Factors binding to <dna>site C</dna> ( <dna>nt 4681 to 4701</dna> ) had a DNA-binding specificity similar to that of factors binding to <dna>site B</dna> , except for <protein>PU.1/Spi-1</protein> .


A GC box containing a binding site for Sp1 was identified ( nt 4623 to 4631 ) .

A <dna>GC box</dna> containing a <dna>binding site</dna> for <protein>Sp1</protein> was identified ( <dna>nt 4623 to 4631</dna> ) .


Site D ( nt 4816 to 4851 ) specifically bound a ubiquitously expressed factor .

<dna>Site D</dna> ( <dna>nt 4816 to 4851</dna> ) specifically bound a <protein>ubiquitously expressed factor</protein> .


These results identify a transcriptional regulatory element associated with a nuclease-hypersensitive site in the pol gene of HIV-1 and suggest that its activity may be controlled by a complex interplay of cis- regulatory elements .

These results identify a <dna>transcriptional regulatory element</dna> associated with a <dna>nuclease-hypersensitive site</dna> in the <dna>pol gene</dna> of HIV-1 and suggest that its activity may be controlled by a complex interplay of cis- <dna>regulatory elements</dna> .


Expression of v-src in T cells correlates with nuclear expression of NF-kappa B .

Expression of <dna>v-src</dna> in <cell_type>T cells</cell_type> correlates with nuclear expression of <protein>NF-kappa B</protein> .


NF-kappa B is a rapidly inducible transcriptional activator that responds to a variety of signals and influences the expression of many genes involved in the immune response .

<protein>NF-kappa B</protein> is a rapidly inducible <dna>transcriptional activator</dna> that responds to a variety of signals and influences the expression of many genes involved in the immune response .


Protein tyrosine kinases transmit signals from cytokine and immune receptors .

Protein <protein>tyrosine kinases</protein> transmit signals from <protein>cytokine and immune receptors</protein> .


Very little information exists linking these two important classes of signaling molecules .

Very little information exists linking these two important classes of <protein>signaling molecules</protein> .


We now demonstrate that v-src expression correlates with nuclear expression of a kappa B binding complex similar to that induced by phorbol ester and ionomycin , as detected by electrophoretic mobility shift assay using a variety of kappa B sites .

We now demonstrate that <dna>v-src</dna> expression correlates with nuclear expression of a <protein>kappa B binding complex</protein> similar to that induced by phorbol ester and ionomycin , as detected by electrophoretic mobility shift assay using a variety of <dna>kappa B sites</dna> .


This complex was blocked by the tyrosine kinase inhibitor , herbimycin A .

This complex was blocked by the <protein>tyrosine kinase</protein> inhibitor , herbimycin A .


The v-src-induced complex comprised the p50 and p65 components of NF-kappa B , as determined by supershift and immunoblot analysis .

The <protein>v-src-induced complex</protein> comprised the <protein>p50</protein> and <protein>p65</protein> components of <protein>NF-kappa B</protein> , as determined by supershift and immunoblot analysis .


As a functional correlate of this finding , transient co-transfection of HIV-1 LTR reporter constructs in a different T cell line demonstrated that v-src activated this promoter in a kappa B-dependent manner .

As a functional correlate of this finding , transient co-transfection of <dna>HIV-1 LTR reporter constructs</dna> in a different <cell_line>T cell line</cell_line> demonstrated that <dna>v-src</dna> activated this <protein>promoter</protein> in a kappa B-dependent manner .


We found that transactivation of the HIV-1 LTR by v-src was more sensitive to mutations of the proximal , rather than the distal , kappa B element .

We found that transactivation of the <dna>HIV-1 LTR</dna> by <dna>v-src</dna> was more sensitive to mutations of the proximal , rather than the distal , <dna>kappa B element</dna> .


The implications for T cell receptor signaling and HIV-1 gene expression are considered .

The implications for <protein>T cell receptor</protein> signaling and <dna>HIV-1 gene</dna> expression are considered .


trans-activation of the HIV promoter by a cDNA and its genomic clones of human herpesvirus-6 .

trans-activation of the <dna>HIV promoter</dna> by a cDNA and its genomic clones of human herpesvirus-6 .


Human herpesvirus 6 ( HHV-6 ) is a lymphotropic herpesvirus , and in vitro , it can productively infect human CD4+ T cells as HIV-1 .

Human herpesvirus 6 ( HHV-6 ) is a lymphotropic herpesvirus , and in vitro , it can productively infect human <cell_line>CD4+ T cells</cell_line> as HIV-1 .


Co-infection of T cells by HIV-1 and HHV-6 can lead to both activation of the HIV-1 promoter and acceleration of the cytopathic effects .

Co-infection of <cell_type>T cells</cell_type> by HIV-1 and HHV-6 can lead to both activation of the <dna>HIV-1 promoter</dna> and acceleration of the cytopathic effects .


An HHV-6 ( GS ) cDNA clone , pCD41 , encoding for a 41-kDa nuclear protein was identified and characterized previously ( Chang and Balachandran , J. Virol. 65 , 2884-2894 and 7085 , 1991 ) .

An <dna>HHV-6 ( GS ) cDNA clone</dna> , <dna>pCD41</dna> , encoding for a <protein>41-kDa nuclear protein</protein> was identified and characterized previously ( Chang and Balachandran , J. Virol. 65 , 2884-2894 and 7085 , 1991 ) .


Sequence analyses show that this protein has significant homology with the human cytomegalovirus UL44 gene coding for the ICP36 family of early-late-class phosphoprotein .

Sequence analyses show that this protein has significant homology with the <dna>human cytomegalovirus UL44 gene</dna> coding for the <protein>ICP36 family</protein> of <protein>early-late-class phosphoprotein</protein> .


Using this cDNA as the probe , a 3.8-kb EcoRI genomic fragment encoding the HHV-6 ( GS ) P41 was cloned and designated as pGD41 .

Using this <dna>cDNA</dna> as the probe , a <dna>3.8-kb EcoRI genomic fragment</dna> encoding the <protein>HHV-6 ( GS ) P41</protein> was cloned and designated as <dna>pGD41</dna> .


When cotransfected with the HIV LTR CAT into CV-1 cells , both the pCD41 and pGD41 clones trans-activated the HIV LTR .

When cotransfected with the <dna>HIV LTR CAT</dna> into <cell_line>CV-1 cells</cell_line> , both the <dna>pCD41</dna> and <dna>pGD41</dna> clones trans-activated the <dna>HIV LTR</dna> .


Sequence analyses of pCD41 indicate that there are two potential open reading frames ( ORFs ) , A and B , which are homologous to the ORFs found in the genomic clone pGD41 .

Sequence analyses of <dna>pCD41</dna> indicate that there are two potential <dna>open reading frames</dna> ( <dna>ORFs</dna> ) , <dna>A</dna> and <dna>B</dna> , which are homologous to the <dna>ORFs</dna> found in the genomic clone <dna>pGD41</dna> .


Deletion constructs of the pCD41 clone demonstrated that ORF-A was critical for the HIV LTR activation .

Deletion constructs of the <dna>pCD41 clone</dna> demonstrated that <protein>ORF-A</protein> was critical for the <dna>HIV LTR</dna> activation .


Deletion analyses of the pCD41 ORF-A and the use of promoter constructs further mapped an internal functional promoter within the pCD41 sequence that can direct the synthesis of the trans-activating protein .

Deletion analyses of the <dna>pCD41</dna> <protein>ORF-A</protein> and the use of <dna>promoter constructs</dna> further mapped an internal functional promoter within the <dna>pCD41</dna> sequence that can direct the synthesis of the <protein>trans-activating protein</protein> .


By using HIV LTR deletion mutants , the NF-kappa B binding sites were found to be critical for response to the pCD41 trans-activation .

By using <dna>HIV LTR deletion mutants</dna> , the <protein>NF-kappa B</protein> <dna>binding sites</dna> were found to be critical for response to the <dna>pCD41</dna> trans-activation .


CD14 -mediated translocation of nuclear factor-kappa B induced by lipopolysaccharide does not require tyrosine kinase activity .

<protein>CD14</protein> -mediated translocation of <protein>nuclear factor-kappa B</protein> induced by lipopolysaccharide does not require <protein>tyrosine kinase</protein> activity .


During the course of serious bacterial infections , lipopolysaccharide ( LPS ) is believed to interact with macrophage receptors , resulting in the generation of inflammatory mediators and systemic symptoms including hemodynamic instability and shock .

During the course of serious bacterial infections , lipopolysaccharide ( LPS ) is believed to interact with <protein>macrophage receptors</protein> , resulting in the generation of inflammatory mediators and systemic symptoms including hemodynamic instability and shock .


CD14 , a glycosylphosphatidylinositol-linked antigen , functions as an LPS signaling receptor .

<protein>CD14</protein> , a <protein>glycosylphosphatidylinositol-linked antigen</protein> , functions as an <protein>LPS signaling receptor</protein> .


A critical issue concerns the mechanism by which CD14 , which has no transmembrane domain , transduces its signal following LPS binding .

A critical issue concerns the mechanism by which <protein>CD14</protein> , which has no <protein>transmembrane domain</protein> , transduces its signal following LPS binding .


Recently , investigators have hypothesized that CD14 -mediated signaling is effected through a receptor-associated tyrosine kinase ( TK ) , suggesting a multicomponent receptor model of LPS signaling .

Recently , investigators have hypothesized that <protein>CD14</protein> -mediated signaling is effected through a receptor-associated <protein>tyrosine kinase</protein> ( TK ) , suggesting a multicomponent receptor model of LPS signaling .


Wild-type Chinese hamster ovary ( CHO ) -K1 cells can be activated by endotoxin to release arachidonate following transfection with human CD14 ( CHO/CD14 ) .

Wild-type <cell_line>Chinese hamster ovary ( CHO ) -K1 cells</cell_line> can be activated by endotoxin to release arachidonate following transfection with human <protein>CD14</protein> ( <protein>CHO/CD14</protein> ) .


Nuclear translocation of cytosolic NF-kappa B is correlated with a number of LPS-inducible responses .


We sought to determine if this pathway were present in CHO/CD14 cells and to elucidate the relationship of NF-kappa B activation to the CD14 receptor system .

We sought to determine if this pathway were present in <cell_line>CHO/CD14 cells</cell_line> and to elucidate the relationship of <protein>NF-kappa B</protein> activation to the <protein>CD14</protein> receptor system .


LPS-stimulated translocation of NF-kappa B in CHO/CD14 cells resembled the same response in the murine macrophage-like cell line RAW 264.7 .

LPS-stimulated translocation of <protein>NF-kappa B</protein> in <cell_line>CHO/CD14 cells</cell_line> resembled the same response in the <cell_line>murine macrophage-like cell line</cell_line> <cell_line>RAW 264.7</cell_line> .


Protein synthesis inhibitors and corticosteroids , which suppress arachidonate release and the synthesis of proinflammatory cytokines , had no effect on translocation of NF-kappa B in CHO/ CD14 or RAW 264.7 cells , demonstrating that NF-kappa B translocation is an early event .

Protein synthesis inhibitors and corticosteroids , which suppress arachidonate release and the synthesis of <protein>proinflammatory cytokines</protein> , had no effect on translocation of <protein>NF-kappa B</protein> in CHO/ <protein>CD14</protein> or <cell_line>RAW 264.7 cells</cell_line> , demonstrating that <protein>NF-kappa B</protein> translocation is an early event .


Although TK activity was consistently observed by immunoblotting extracts from activated RAW 264.7 cells , LPS-induced phosphotyrosine residues were not observed from similarly treated CHO/CD14 cells .

Although TK activity was consistently observed by immunoblotting extracts from activated <cell_line>RAW 264.7 cells</cell_line> , LPS-induced phosphotyrosine residues were not observed from similarly treated <cell_line>CHO/CD14 cells</cell_line> .


Furthermore , the TK inhibitors herbimycin A and genistein failed to inhibit translocation of NF-kappa B in CHO/CD14 or RAW 264.7 cells , although both of these agents inhibited LPS-induced TK activity in RAW 264.7 cells .

Furthermore , the TK inhibitors herbimycin A and genistein failed to inhibit translocation of <protein>NF-kappa B</protein> in <cell_line>CHO/CD14</cell_line> or <cell_line>RAW 264.7 cells</cell_line> , although both of these agents inhibited LPS-induced TK activity in <cell_line>RAW 264.7 cells</cell_line> .


These results imply that TK activity is not obligatory for CD14 -mediated signal transduction to occur in response to LPS .

These results imply that TK activity is not obligatory for <protein>CD14</protein> -mediated signal transduction to occur in response to LPS .


Signals transduced through the CD4 molecule on T lymphocytes activate NF-kappa B .

Signals transduced through the <protein>CD4 molecule</protein> on <cell_type>T lymphocytes</cell_type> activate <protein>NF-kappa B</protein> .


We have demonstrated that native envelope glycoproteins of HIV-1 , gp160 can induce activation of the transcription factor , NF-kappa B .

We have demonstrated that <protein>native envelope glycoproteins</protein> of HIV-1 , gp160 can induce activation of the <protein>transcription factor</protein> , <protein>NF-kappa B</protein> .


The stimulatory effects of gp160 are mediated through the CD4 molecule , since pretreatment with soluble CD4 abrogates its activity .

The stimulatory effects of gp160 are mediated through the <protein>CD4 molecule</protein> , since pretreatment with soluble <protein>CD4</protein> abrogates its activity .


The gp160-induced NF-kappa B complex consists of p65 , p50 and c-rel proteins .

The <protein>gp160-induced NF-kappa B complex</protein> consists of <protein>p65</protein> , <protein>p50</protein> and <protein>c-rel proteins</protein> .


The stimulatory effect of gp160 on NF-kappa B activation is protein synthesis independent , is dependent upon protein tyrosine phosphorylation , and abrogated by inhibitors of protein kinase C .

The stimulatory effect of gp160 on <protein>NF-kappa B</protein> activation is protein synthesis independent , is dependent upon protein tyrosine phosphorylation , and abrogated by inhibitors of <protein>protein kinase C</protein> .


The gp160-mediated activation of NF-kappa B in CD4 positive T cells may be involved in biological effects , e.g. , enhanced HIV replication , hypergammaglobulinemia , increased cytokine secretion , hypercellularity in bone marrow and apoptosis .

The gp160-mediated activation of <protein>NF-kappa B</protein> in <cell_type>CD4 positive T cells</cell_type> may be involved in biological effects , e.g. , enhanced HIV replication , hypergammaglobulinemia , increased <protein>cytokine</protein> secretion , hypercellularity in bone marrow and apoptosis .


No evidence for the expression of the progesterone receptor on peripheral blood lymphocytes during pregnancy [ see comments ]

No evidence for the expression of the <protein>progesterone receptor</protein> on <cell_type>peripheral blood lymphocytes</cell_type> during pregnancy [ see comments ]


The expression of the progesterone receptor in human peripheral blood lymphocytes was analysed , using an enzyme linked immunosorbent assay ( Abbott PgR-EIA monoclonal ) , in order to evaluate its prognostic character in the context of spontaneous abortion .

The expression of the <protein>progesterone receptor</protein> in <cell_type>human peripheral blood lymphocytes</cell_type> was analysed , using an enzyme linked immunosorbent assay ( Abbott PgR-EIA monoclonal ) , in order to evaluate its prognostic character in the context of spontaneous abortion .


Cytosols were prepared from lymphocytes of 24 healthy pregnant women ( 11 first , 10 second and three third trimester ) , seven healthy non-pregnant women , nine women with recurrent spontaneous abortion , and six healthy men .


In addition , a human breast carcinoma cell line ( ZR-75-1 ) , which expresses the progesterone receptor , was analysed throughout .

In addition , a <cell_line>human breast carcinoma cell line</cell_line> ( <cell_line>ZR-75-1</cell_line> ) , which expresses the <protein>progesterone receptor</protein> , was analysed throughout .


The ZR-75-1 cell line showed an expression of 642 fmol/mg whereas lymphocytes of pregnant women showed an expression < or = 4 fmol/mg .

The <cell_line>ZR-75-1 cell line</cell_line> showed an expression of 642 fmol/mg whereas lymphocytes of pregnant women showed an expression < or = 4 fmol/mg .


Lymphocytes of non-pregnant women , women with threatened pre-term delivery , and men showed equivalent levels : 3 +/- 1 , 3 +/- 2 and 5 +/- 4 fmol/mg respectively .

<cell_type>Lymphocytes</cell_type> of non-pregnant women , women with threatened pre-term delivery , and men showed equivalent levels : 3 +/- 1 , 3 +/- 2 and 5 +/- 4 fmol/mg respectively .


These results show that there is no evidence of specific expression of the progesterone receptor in pregnancy and exclude any prognostic character in spontaneous abortion .

These results show that there is no evidence of specific expression of the <protein>progesterone receptor</protein> in pregnancy and exclude any prognostic character in spontaneous abortion .


A role for the progesterone receptor in the mechanism of the known effect of progesterone on peripheral blood lymphocytes is also excluded .

A role for the <protein>progesterone receptor</protein> in the mechanism of the known effect of progesterone on <cell_type>peripheral blood lymphocytes</cell_type> is also excluded .


Tolerance to lipopolysaccharide involves mobilization of nuclear factor kappa B with predominance of p50 homodimers .

Tolerance to lipopolysaccharide involves mobilization of <protein>nuclear factor kappa B</protein> with predominance of <protein>p50</protein> homodimers .


Stimulation of the human monocytic cell line Mono Mac 6 with lipopolysaccharide ( LPS ) leads to rapid and transient expression of cytokines like tumor necrosis factor ( TNF ) .

Stimulation of the <cell_line>human monocytic cell line</cell_line> <cell_line>Mono Mac 6</cell_line> with lipopolysaccharide ( LPS ) leads to rapid and transient expression of <protein>cytokines</protein> like <protein>tumor necrosis factor</protein> ( <protein>TNF</protein> ) .


When such cells are precultured for 2 days with a low dose of LPS ( 20 ng/ml ) followed by stimulation with a high dose of LPS ( 1 microgram/ml ) , expression of the TNF gene is minimal , i.e. the cells are tolerant .

When such cells are precultured for 2 days with a low dose of LPS ( 20 ng/ml ) followed by stimulation with a high dose of LPS ( 1 microgram/ml ) , expression of the <dna>TNF gene</dna> is minimal , i.e. the cells are tolerant .


In nuclear run-on analysis , such tolerant cells show only a low degree of transcription , indicating that tolerance operates at or upstream of the transcription level .

In nuclear run-on analysis , such <cell_type>tolerant cells</cell_type> show only a low degree of transcription , indicating that tolerance operates at or upstream of the transcription level .


The CD14 LPS receptor is , however , up-regulated ( not down-regulated ) in tolerant cells , and LPS can , in fact , still lead to activation of tolerant cells as evidenced by mobilization of the transcription factor nuclear factor kappa B ( NF-kappa B ) .

The <protein>CD14</protein> LPS receptor is , however , up-regulated ( not down-regulated ) in <cell_line>tolerant cells</cell_line> , and LPS can , in fact , still lead to activation of <cell_line>tolerant cells</cell_line> as evidenced by mobilization of the <protein>transcription factor</protein> <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) .


Resolution of the NF-kappa B complex in gel shift analysis shows that the binding protein , mobilized in naive Mono Mac 6 cells , consists mainly of p50-p65 heterodimers , while in tolerant cells , the p50 homodimer is predominant .

Resolution of the <protein>NF-kappa B complex</protein> in gel shift analysis shows that the <protein>binding protein</protein> , mobilized in <cell_line>naive Mono Mac 6 cells</cell_line> , consists mainly of <protein>p50-p65 heterodimers</protein> , while in <cell_line>tolerant cells</cell_line> , the <protein>p50 homodimer</protein> is predominant .


This increase in p50 homodimers coincides with an increase in p105 mRNA , suggestive of a transcriptional up-regulation of p50 .

This increase in <protein>p50 homodimers</protein> coincides with an increase in <rna>p105 mRNA</rna> , suggestive of a transcriptional up-regulation of <protein>p50</protein> .


Reporter gene analysis reveals that the NF-kappa B complex mobilized in tolerant cells is functionally inactive in that NF-kappa B-dependent luciferase constructs containing the human immunodeficiency virus long terminal repeat or the TNF 5'-region show only minimal transactivation after LPS stimulation .

Reporter gene analysis reveals that the <protein>NF-kappa B complex</protein> mobilized in <cell_line>tolerant cells</cell_line> is functionally inactive in that <dna>NF-kappa B-dependent luciferase constructs</dna> containing the <dna>human immunodeficiency virus long terminal repeat</dna> or the <dna>TNF 5'-region</dna> show only minimal transactivation after LPS stimulation .


Similar to Mono Mac 6 cells , primary blood monocytes , when precultured with a low dose of LPS , also become tolerant and produce little TNF after LPS stimulation .

Similar to <cell_line>Mono Mac 6 cells</cell_line> , <cell_type>primary blood monocytes</cell_type> , when precultured with a low dose of LPS , also become tolerant and produce little <protein>TNF</protein> after LPS stimulation .


The tolerant blood monocytes also up-regulate CD14 , and they mobilize NF-kappa B with a predominance of p50 homodimers .

The <cell_type>tolerant blood monocytes</cell_type> also up-regulate <protein>CD14</protein> , and they mobilize <protein>NF-kappa B</protein> with a predominance of <protein>p50 homodimers</protein> .


Taken together , these results demonstrate that tolerance to LPS is determined by post-receptor mechanisms that involve an altered composition of the NF-kappa B complex .

Taken together , these results demonstrate that tolerance to LPS is determined by post-receptor mechanisms that involve an altered composition of the <protein>NF-kappa B complex</protein> .


Analysis of Oct2-isoform expression in lipopolysaccharide-stimulated B lymphocytes .

Analysis of <protein>Oct2-isoform</protein> expression in <cell_line>lipopolysaccharide-stimulated B lymphocytes</cell_line> .


Oct2-isoform expression in splenic B cells stimulated with lipopolysaccharide or lipopolysaccharide plus phorbol-di-butyrate was analysed by cDNA cloning .

<protein>Oct2-isoform</protein> expression in <cell_type>splenic B cells</cell_type> stimulated with lipopolysaccharide or lipopolysaccharide plus phorbol-di-butyrate was analysed by cDNA cloning .


The frequency of Oct2-positive clones was 1/15 , 000 in both libraries .

The frequency of <cell_line>Oct2-positive clones</cell_line> was 1/15 , 000 in both libraries .


Two new isoforms were found that generate novel amino- or carboxy-terminal sequences .

Two new isoforms were found that generate novel <protein>amino- or carboxy-terminal sequences</protein> .


An isoform lacking exon 11 destroyed the carboxy-terminal leucin-zipper region and introduced a frame shift creating a novel , proline-rich carboxy terminus .

An isoform lacking <dna>exon 11</dna> destroyed the <protein>carboxy-terminal leucin-zipper region</protein> and introduced a frame shift creating a novel , <protein>proline-rich carboxy terminus</protein> .


A new exon containing a highly basic region ( 4c ) was characterized , between exons 4 and 5 .

A new <dna>exon</dna> containing a highly basic region ( 4c ) was characterized , <dna>between exons 4 and 5</dna> .


This exon was inserted between glutamine-rich regions 2 and 3 , carboxy terminal of a tentative leucine-zipper structure .

This exon was inserted <dna>between glutamine-rich regions 2 and 3</dna> , <protein>carboxy terminal</protein> of a tentative <protein>leucine-zipper structure</protein> .


In addition , a new combination isoform containing Oct2a 's amino terminal insert ( exon 7a ) and Oct2b 's carboxy terminal insert ( exon 13 ) was found that created a novel large isoform , Oct2ab .

In addition , a new combination isoform containing <protein>Oct2a 's amino terminal insert</protein> ( <dna>exon 7a</dna> ) and <protein>Oct2b 's carboxy terminal insert</protein> ( <dna>exon 13</dna> ) was found that created a novel large isoform , <protein>Oct2ab</protein> .


More frequent use of the classical Oct2a and Oct2b isoforms was observed in the lipopolysaccharide-stimulated B cells , while a preference for the Oct2ab and Oct2ba isoforms was observed in lipopolysaccharide plus phorbol-di-butyrate-treated cells .

More frequent use of the classical <protein>Oct2a</protein> and <protein>Oct2b</protein> isoforms was observed in the <cell_line>lipopolysaccharide-stimulated B cells</cell_line> , while a preference for the <protein>Oct2ab</protein> and <protein>Oct2ba</protein> isoforms was observed in <cell_line>lipopolysaccharide plus phorbol-di-butyrate-treated cells</cell_line> .


Positive regulators of the lineage-specific transcription factor GATA-1 in differentiating erythroid cells .

Positive regulators of the lineage-specific <protein>transcription factor</protein> <protein>GATA-1</protein> in <cell_type>differentiating erythroid cells</cell_type> .


The zinc finger transcription factor GATA-1 is a major regulator of gene expression in erythroid , megakaryocyte , and mast cell lineages .

The <protein>zinc finger transcription factor</protein> <protein>GATA-1</protein> is a major regulator of gene expression in <cell_type>erythroid , megakaryocyte , and mast cell lineages</cell_type> .


GATA-1 binds to WGATAR consensus motifs in the regulatory regions of virtually all erythroid cell-specific genes .

<protein>GATA-1</protein> binds to <dna>WGATAR consensus motifs</dna> in the <dna>regulatory regions</dna> of virtually all <dna>erythroid cell-specific genes</dna> .


Analyses with cultured cells and cell-free systems have provided strong evidence that GATA-1 is involved in control of globin gene expression during erythroid differentiation .

Analyses with <cell_line>cultured cells</cell_line> and cell-free systems have provided strong evidence that <protein>GATA-1</protein> is involved in control of <dna>globin gene</dna> expression during erythroid differentiation .


Targeted mutagenesis of the GATA-1 gene in embryonic stem cells has demonstrated its requirement in normal erythroid development .

Targeted mutagenesis of the <dna>GATA-1 gene</dna> in <cell_type>embryonic stem cells</cell_type> has demonstrated its requirement in normal erythroid development .


Efficient rescue of the defect requires an intact GATA element in the distal promoter , suggesting autoregulatory control of GATA-1 transcription .

Efficient rescue of the defect requires an intact <dna>GATA element</dna> in the <dna>distal promoter</dna> , suggesting autoregulatory control of <protein>GATA-1</protein> transcription .


To examine whether GATA-1 expression involves additional regulatory factors or is maintained entirely by an autoregulatory loop , we have used a transient heterokaryon system to test the ability of erythroid factors to activate the GATA-1 gene in nonerythroid nuclei .

To examine whether <protein>GATA-1</protein> expression involves additional <protein>regulatory factors</protein> or is maintained entirely by an autoregulatory loop , we have used a transient heterokaryon system to test the ability of <protein>erythroid factors</protein> to activate the <dna>GATA-1 gene</dna> in nonerythroid nuclei .


We show here that proerythroblasts and mature erythroid cells contain a diffusible activity ( TAG ) capable of transcriptional activation of GATA-1 and that this activity decreases during the terminal differentiation of erythroid cells .

We show here that <cell_type>proerythroblasts</cell_type> and <cell_type>mature erythroid cells</cell_type> contain a diffusible activity ( TAG ) capable of transcriptional activation of <protein>GATA-1</protein> and that this activity decreases during the terminal differentiation of <cell_type>erythroid cells</cell_type> .


Nuclei from GATA-1 -mutant embryonic stem cells can still be reprogrammed to express their globin genes in erythroid heterokaryons , indicating that de novo induction of GATA-1 is not required for globin gene activation following cell fusion .

Nuclei from <cell_line>GATA-1 -mutant embryonic stem cells</cell_line> can still be reprogrammed to express their <dna>globin genes</dna> in <cell_type>erythroid heterokaryons</cell_type> , indicating that de novo induction of <protein>GATA-1</protein> is not required for <dna>globin gene</dna> activation following cell fusion .


Role of HIV-1 Nef expression in activation pathways in CD4 + T cells .

Role of <protein>HIV-1 Nef</protein> expression in activation pathways in <protein>CD4</protein> + T cells .


The role of the human immunodeficiency virus ( HIV-1 ) Nef protein in T cell activation pathways was investigated using a Jurkat CD4+ cell line stably transfected with a Nef expression vector .

The role of the <protein>human immunodeficiency virus ( HIV-1 ) Nef protein</protein> in T cell activation pathways was investigated using a <cell_line>Jurkat CD4+ cell line</cell_line> stably transfected with a Nef expression vector .


Secretion of IL-2 and TNF-alpha , surface expression of IL-2R , and DNA-binding activity of NF-kappa B and AP-1 ( Fos/Jun ) complex in response to phorbol myristate acetate , TNF-alpha , or immobilized antibodies to CD3 were monitored .

Secretion of <protein>IL-2</protein> and <protein>TNF-alpha</protein> , surface expression of <protein>IL-2R</protein> , and DNA-binding activity of <protein>NF-kappa B</protein> and <protein>AP-1 ( Fos/Jun ) complex</protein> in response to phorbol myristate acetate , <protein>TNF-alpha</protein> , or immobilized antibodies to <protein>CD3</protein> were monitored .


These parameters were not modified by Nef expression in Jurkat cells , whereas stimulation with the same stimuli resulted in partial inhibition of LTR activation in Nef+ Jurkat cells .

These parameters were not modified by <protein>Nef</protein> expression in <cell_line>Jurkat cells</cell_line> , whereas stimulation with the same stimuli resulted in partial inhibition of <dna>LTR</dna> activation in <cell_line>Nef+ Jurkat cells</cell_line> .


This inhibition was not mediated through Nef phosphorylation on Thr-15 or GTP-binding activity because mutations in critical sites did not alter this inhibition .

This inhibition was not mediated through <protein>Nef</protein> phosphorylation on Thr-15 or GTP-binding activity because mutations in critical sites did not alter this inhibition .


Analysis of truncated LTRs confirmed that inhibition of LTR activation was not mediated through NF-kappa B -binding activity but through the region containing the negative responding elements ( NREs ) .

Analysis of truncated <dna>LTRs</dna> confirmed that inhibition of <dna>LTR</dna> activation was not mediated through <protein>NF-kappa B</protein> -binding activity but through the region containing the <dna>negative responding elements</dna> ( <dna>NREs</dna> ) .


These results suggest that Nef downmodulates LTR activation without significantly inhibiting the capacity of T cells to respond to immunological activations .

These results suggest that <protein>Nef</protein> downmodulates <dna>LTR</dna> activation without significantly inhibiting the capacity of <cell_type>T cells</cell_type> to respond to immunological activations .


Tat-binding protein 7 is a subunit of the 26S protease .

<protein>Tat-binding protein 7</protein> is a subunit of the <protein>26S protease</protein> .


Subunit 6 ( S6 ) , an integral component of the 26S protease from human erythrocytes , has been studied by SDS-PAGE , peptide mapping and sequence analysis .

<protein>Subunit 6</protein> ( <protein>S6</protein> ) , an integral component of the <protein>26S protease</protein> from <cell_type>human erythrocytes</cell_type> , has been studied by SDS-PAGE , peptide mapping and sequence analysis .


S6 was cleaved with CNBr and three internal peptides were sequenced .

<protein>S6</protein> was cleaved with <protein>CNBr</protein> and three internal peptides were sequenced .


A comparison with known proteins in Genbank revealed that all three S6 peptides match the predicted sequence of TBP7 , Tat-binding protein 7 .

A comparison with known proteins in Genbank revealed that all three <protein>S6</protein> peptides match the predicted sequence of <protein>TBP7</protein> , <protein>Tat-binding protein 7</protein> .


Based on peptide matches covering more than 10 % of the TBP7 sequence , and the fact that the migration of S6 on SDS-PAGE is consistent with the estimated molecular mass for TBP7 , we conclude that subunit 6 of the 26S protease is TBP7 .

Based on peptide matches covering more than 10 % of the <protein>TBP7</protein> sequence , and the fact that the migration of <protein>S6</protein> on SDS-PAGE is consistent with the estimated molecular mass for <protein>TBP7</protein> , we conclude that <protein>subunit 6</protein> of the <protein>26S protease</protein> is <protein>TBP7</protein> .


Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues .

Hypoxia causes the activation of <protein>nuclear factor kappa B</protein> through the phosphorylation of <protein>I kappa B alpha</protein> on tyrosine residues .


The response of mammalian cells to stress is controlled by transcriptional regulatory proteins such as nuclear factor kappa B ( NF-kappa B ) to induce a wide variety of early response genes .

The response of <cell_type>mammalian cells</cell_type> to stress is controlled by <protein>transcriptional regulatory proteins</protein> such as <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) to induce a wide variety of <dna>early response genes</dna> .


In this report , we show that exposure of cells to hypoxia ( 0.02 % O2 ) results in I kappa B alpha degradation , increased NF-kappa B DNA binding activity , and transactivation of a reporter gene construct containing two NF-kappa B DNA binding sites .

In this report , we show that exposure of cells to hypoxia ( 0.02 % O2 ) results in <protein>I kappa B alpha</protein> degradation , increased <protein>NF-kappa B</protein> DNA binding activity , and transactivation of a <dna>reporter gene construct</dna> containing two <dna>NF-kappa B DNA binding sites</dna> .


Pretreatment of cells with protein tyrosine kinase inhibitors and the dominant negative allele of c-Raf-1 ( Raf 301 ) inhibited I kappa B alpha degradation , NF-kappa B binding , and transactivation of kappa B reporter constructs by hypoxia .

Pretreatment of cells with protein <protein>tyrosine kinase</protein> inhibitors and the <dna>dominant negative allele</dna> of <dna>c-Raf-1</dna> ( <protein>Raf 301</protein> ) inhibited <protein>I kappa B alpha</protein> degradation , <protein>NF-kappa B</protein> binding , and transactivation of <dna>kappa B reporter constructs</dna> by hypoxia .


To demonstrate a direct link between changes in the phosphorylation pattern of I kappa B alpha with NF-kappa B activation , we immunoprecipitated I kappa B alpha after varying times of hypoxic exposure and found that its tyrosine phosphorylation status increased during hypoxic exposure .

To demonstrate a direct link between changes in the phosphorylation pattern of <protein>I kappa B alpha</protein> with <protein>NF-kappa B</protein> activation , we immunoprecipitated <protein>I kappa B alpha</protein> after varying times of hypoxic exposure and found that its tyrosine phosphorylation status increased during hypoxic exposure .


Inhibition of the transfer of tyrosine phosphoryl groups onto I kappa B alpha prevented I kappa B alpha degradation and NF-kappa B binding .

Inhibition of the transfer of tyrosine phosphoryl groups onto <protein>I kappa B alpha</protein> prevented <protein>I kappa B alpha</protein> degradation and <protein>NF-kappa B</protein> binding .


In comparison to other activators of NF-kappa B such as phorbol myristate acetate or tumor necrosis factor , we did not detect changes in the tyrosine phosphorylation status of I kappa B alpha following treatment with either of these agents .

In comparison to other activators of <protein>NF-kappa B</protein> such as phorbol myristate acetate or <protein>tumor necrosis factor</protein> , we did not detect changes in the tyrosine phosphorylation status of <protein>I kappa B alpha</protein> following treatment with either of these agents .


These results suggest that tyrosine phosphorylation of I kappa B alpha during hypoxia is an important proximal step which precedes its dissociation and degradation from NF-kappa B .

These results suggest that tyrosine phosphorylation of <protein>I kappa B alpha</protein> during hypoxia is an important proximal step which precedes its dissociation and degradation from <protein>NF-kappa B</protein> .


Overproduction of NFKB2 ( lyt-10 ) and c-Rel : a mechanism for HTLV-I Tax -mediated trans-activation via the NF-kappa B signalling pathway .

Overproduction of <protein>NFKB2</protein> ( <protein>lyt-10</protein> ) and <protein>c-Rel</protein> : a mechanism for <protein>HTLV-I Tax</protein> -mediated trans-activation via the <protein>NF-kappa B</protein> signalling pathway .


Molecular , biochemical and epidemiological evidence implicate HTLV-I as an etiologic agent of adult T cell leukemia ( ATL ) .


The Tax protein of HTLV-I , a positive transcriptional activator of HTLV-I gene expression , is a viral oncogene that also increases transcription of cellular genes including GM-CSF , IL-2R alpha and IL-2 .

The <protein>Tax protein</protein> of HTLV-I , a <protein>positive transcriptional activator</protein> of HTLV-I gene expression , is a viral oncogene that also increases transcription of <dna>cellular genes</dna> including <protein>GM-CSF</protein> , <protein>IL-2R alpha</protein> and <protein>IL-2</protein> .


One of the cellular targets of the trans-activating effects of Tax is the NF-kappa B/Rel family of transcription factors , pleiotropic regulators of immunoregulatory , cytokine and viral gene expression .

One of the cellular targets of the trans-activating effects of Tax is the <protein>NF-kappa B/Rel family</protein> of <protein>transcription factors</protein> , <protein>pleiotropic regulators</protein> of immunoregulatory , cytokine and viral gene expression .


In this report , we demonstrate that NFKB2 ( lyt-10 ) and c-Rel are overexpressed in HTLV-I infected and Tax-expressing cells and , together , account for the majority of the constitutive NF-kappa B binding activity in these cells before and after PMA stimulation .

In this report , we demonstrate that <protein>NFKB2</protein> ( <protein>lyt-10</protein> ) and <protein>c-Rel</protein> are overexpressed in HTLV-I infected and <cell_type>Tax-expressing cells</cell_type> and , together , account for the majority of the constitutive <protein>NF-kappa B</protein> binding activity in these cells before and after PMA stimulation .


Most importantly , we show a Tax -dependent correlation between expression of NFKB2 ( p100 ) and processing to the DNA binding NFKB2 ( p52 ) form , induction of c-Rel , and trans-activation of NF-kappa B -mediated gene expression .

Most importantly , we show a <protein>Tax</protein> -dependent correlation between expression of <protein>NFKB2</protein> ( <protein>p100</protein> ) and processing to the DNA binding <protein>NFKB2</protein> ( <protein>p52</protein> ) form , induction of <protein>c-Rel</protein> , and trans-activation of <protein>NF-kappa B</protein> -mediated gene expression .


Furthermore , the NFKB2 precursor is physically associated with c-Rel and with Tax in HTLV-I infected cells .

Furthermore , the <protein>NFKB2</protein> precursor is physically associated with <protein>c-Rel</protein> and with <protein>Tax</protein> in <cell_type>HTLV-I infected cells</cell_type> .


We propose that NFKB2 synthesis and processing allows continuous nuclear expression of an otherwise cytoplasmic protein and , in conjunction with overexpression of c-Rel , NFKB2 alters the NF-kappa B signalling pathway and contributes to leukemic transformation of T cells by HTLV-I .

We propose that <protein>NFKB2</protein> synthesis and processing allows continuous nuclear expression of an otherwise <protein>cytoplasmic protein</protein> and , in conjunction with overexpression of <protein>c-Rel</protein> , <protein>NFKB2</protein> alters the <protein>NF-kappa B</protein> signalling pathway and contributes to leukemic transformation of <cell_type>T cells</cell_type> by HTLV-I .


Retinoic acid downmodulates erythroid differentiation and GATA1 expression in purified adult-progenitor culture .

Retinoic acid downmodulates erythroid differentiation and <protein>GATA1</protein> expression in <cell_line>purified adult-progenitor culture</cell_line> .


All-trans retinoic acid ( RA ) is an important morphogen in vertebrate development , a normal constituent in human adult blood and is also involved in the control of cell growth and differentiation in acute promyelocytic leukemia .


We have examined the effects of RA on normal hematopoiesis by using early hematopoietic progenitor cells ( HPC ) stringently purified from adult peripheral blood .

We have examined the effects of RA on normal hematopoiesis by using early <cell_type>hematopoietic progenitor cells</cell_type> ( <cell_type>HPC</cell_type> ) stringently purified from adult peripheral blood .


In clonogenetic fetal calf serum-supplemented ( FCS+ ) or -nonsupplemented ( FCS- ) culture treated with saturating levels of interleukin-3 ( IL-3 ) granulocyte-macrophage colony-stimulating factor ( GM-CSF ) and erythropoietin ( Ep ) ( combined with c-kit ligand in FCS ( - ) -culture conditions ) , RA induces a dramatic dose-dependent shift from erythroid to granulomonocytic colony formation , the latter colonies being essentially represented by granulocytic clones .

In <cell_line>clonogenetic fetal calf serum-supplemented ( FCS+ ) or -nonsupplemented ( FCS- ) culture</cell_line> treated with saturating levels of <protein>interleukin-3</protein> ( <protein>IL-3</protein> ) <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) and <protein>erythropoietin</protein> ( <protein>Ep</protein> ) ( combined with <protein>c-kit</protein> ligand in FCS ( - ) -culture conditions ) , RA induces a dramatic dose-dependent shift from erythroid to granulomonocytic colony formation , the latter colonies being essentially represented by <cell_line>granulocytic clones</cell_line> .


This shift is apparently not caused by a recruitment phenomenon , because in FCS+ culture , the total number of colonies is not significantly modified by RA addition .

This shift is apparently not caused by a recruitment phenomenon , because in <cell_line>FCS+ culture</cell_line> , the total number of colonies is not significantly modified by RA addition .


In FCS- liquid-suspension culture supplemented with saturating Ep level and low-dose IL-3/GM-CSF , adult HPC undergo unilineage erythropoietic differentiation : Here again , treatment with high-dose RA induces a shift from the erythroid to granulocytic differentiation pathway .

In <cell_line>FCS- liquid-suspension culture</cell_line> supplemented with saturating <protein>Ep</protein> level and <protein>low-dose IL-3/GM-CSF</protein> , adult <cell_type>HPC</cell_type> undergo unilineage erythropoietic differentiation : Here again , treatment with high-dose RA induces a shift from the erythroid to granulocytic differentiation pathway .


Studies on RA time-response or pulse treatment in semisolid or liquid culture show that early RA addition is most effective , thus indicating that early but not late HPC are sensitive to its action .

Studies on RA time-response or pulse treatment in semisolid or liquid culture show that early RA addition is most effective , thus indicating that early but not late <cell_type>HPC</cell_type> are sensitive to its action .


We then analyzed the expression of the master GATA1 gene , which encodes a finger transcription factor required for normal erythroid development ; addition of RA to HPC stimulated into unilineage erythropoietic differentiation in liquid culture caused a virtually complete inhibition of GATA1 mRNA induction .

We then analyzed the expression of the <dna>master GATA1 gene</dna> , which encodes a <protein>finger transcription factor</protein> required for normal erythroid development ; addition of RA to <cell_type>HPC</cell_type> stimulated into unilineage erythropoietic differentiation in liquid culture caused a virtually complete inhibition of <rna>GATA1 mRNA</rna> induction .


These results indicate that RA directly inhibits the erythroid differentiation program at the level of early adult HPC , and may lead to a shift from the erythroid to granulocytic differentiation pathway .

These results indicate that RA directly inhibits the erythroid differentiation program at the level of early adult <cell_type>HPC</cell_type> , and may lead to a shift from the erythroid to granulocytic differentiation pathway .


This phenomenon is correlated with inhibition of GATA1 induction in the early stages of erythropoietic differentiation .

This phenomenon is correlated with inhibition of <protein>GATA1</protein> induction in the early stages of erythropoietic differentiation .


Induction of phosphatidylinositol turnover and EGR-1 mRNA expression by crosslinking of surface IgM and IgD in the human B cell line B104 .

Induction of phosphatidylinositol turnover and <rna>EGR-1 mRNA</rna> expression by crosslinking of surface <protein>IgM</protein> and <protein>IgD</protein> in the <cell_line>human B cell line B104</cell_line> .


We have previously shown that a human B lymphoma cell line , B104 , expressed surface IgM ( sIgM ) and surface IgD ( sIgD ) , and that crosslinking of sIgM and sIgD by anti-IgM antibody ( Ab ) and anti-IgD Ab , respectively , induced Ca2+ influx to almost the same degree , whereas only sIgM -crosslinking caused B104 cell death .

We have previously shown that a <cell_line>human B lymphoma cell line , B104</cell_line> , expressed <protein>surface IgM</protein> ( <protein>sIgM</protein> ) and <protein>surface IgD</protein> ( <protein>sIgD</protein> ) , and that crosslinking of <protein>sIgM</protein> and <protein>sIgD</protein> by <protein>anti-IgM antibody ( Ab )</protein> and <protein>anti-IgD Ab</protein> , respectively , induced Ca2+ influx to almost the same degree , whereas only <protein>sIgM</protein> -crosslinking caused <cell_line>B104 cell</cell_line> death .


Here , we investigated the accumulation of cyclic AMP ( cAMP ) , the hydrolysis of inositol phosphates , protein kinase C ( PKC ) activity and the induction of Egr-1 and c-fos mRNA expression by sIgM- and sIgD-crosslinking to examine differences in the signals mediated through sIgM and sIgD in B104 cells .

Here , we investigated the accumulation of cyclic AMP ( cAMP ) , the hydrolysis of inositol phosphates , <protein>protein kinase C</protein> ( <protein>PKC</protein> ) activity and the induction of Egr-1 and c-fos mRNA expression by sIgM- and sIgD-crosslinking to examine differences in the signals mediated through <protein>sIgM</protein> and <protein>sIgD</protein> in <cell_line>B104 cells</cell_line> .


Both sIgM- and sIgD-crosslinking with antibodies induced elevation of cAMP levels , phosphatidylinositol turnover , PKC activation and expression of Egr-1 and c-fos mRNA , although sIgM -crosslinking was more effective than sIgD -crosslinking , presumably due to the higher expression of sIgM than of sIgD .

Both sIgM- and sIgD-crosslinking with antibodies induced elevation of cAMP levels , phosphatidylinositol turnover , <protein>PKC</protein> activation and expression of <rna>Egr-1 and c-fos mRNA</rna> , although <protein>sIgM</protein> -crosslinking was more effective than <protein>sIgD</protein> -crosslinking , presumably due to the higher expression of <protein>sIgM</protein> than of <protein>sIgD</protein> .


Egr-1 mRNA expression induced by sIgM- and sIgD-crosslinking was inhibited by H7 , erbstatin and genistein , but not by HA1004 .

<rna>Egr-1 mRNA</rna> expression induced by sIgM- and sIgD-crosslinking was inhibited by <protein>H7</protein> , erbstatin and genistein , but not by HA1004 .


Erbstatin and genistein inhibited the sIg-crosslinking-induced Egr-1 mRNA expression in a dose-dependent manner parallel to that observed in the inhibition of sIg-crosslinking-induced protein tyrosine phosphorylation .

Erbstatin and genistein inhibited the sIg-crosslinking-induced <rna>Egr-1 mRNA</rna> expression in a dose-dependent manner parallel to that observed in the inhibition of sIg-crosslinking-induced protein tyrosine phosphorylation .


Phorbol myristate acetate induced Egr-1 mRNA expression but forskolin and dibutyryl cyclic AMP did not .

Phorbol myristate acetate induced <rna>Egr-1 mRNA</rna> expression but forskolin and dibutyryl cyclic AMP did not .


These findings suggest that the Egr-1 mRNA activating signals through sIgM and sIgD are protein tyrosine kinase- and PKC-dependent , but protein kinase A -independent .

These findings suggest that the <rna>Egr-1 mRNA</rna> activating signals through <protein>sIgM</protein> and <protein>sIgD</protein> are protein tyrosine kinase- and PKC-dependent , but <protein>protein kinase A</protein> -independent .


Cyclosporin A ( CsA ) and FK506 rescued B104 cells from death induced by anti-IgM Ab , but did not affect the expression of Egr-1 and c-fos mRNA , showing that CsA and FK506 affect signal transducers differently from or downstream to these molecules .

Cyclosporin A ( CsA ) and FK506 rescued <cell_line>B104 cells</cell_line> from death induced by <protein>anti-IgM Ab</protein> , but did not affect the expression of <protein>Egr-1</protein> and <rna>c-fos mRNA</rna> , showing that CsA and FK506 affect signal transducers differently from or downstream to these molecules .


The difference in signals transduced through sIgM and sIgD in B104 cells is discussed .

The difference in signals transduced through <protein>sIgM</protein> and <protein>sIgD</protein> in <cell_line>B104 cells</cell_line> is discussed .


Direct exposure to 2 , 3 , 7 , 8-tetrachlorodibenzo-p-dioxin ( TCDD ) increases infectivity of human erythrocytes to a malarial parasite .

Direct exposure to 2 , 3 , 7 , 8-tetrachlorodibenzo-p-dioxin ( TCDD ) increases infectivity of <cell_type>human erythrocytes</cell_type> to a malarial parasite .


Direct exposure to 10 nM 2 , 3 , 7 , 8-TCDD caused a 75 % increase and a 2-fold increase in the infectivity of isolated human erythrocytes to P. falciparum after 48 hours when the parasites were in an unsynchronized or synchronized state of growth , respectively .

Direct exposure to 10 nM 2 , 3 , 7 , 8-TCDD caused a 75 % increase and a 2-fold increase in the infectivity of isolated <cell_type>human erythrocytes</cell_type> to P. falciparum after 48 hours when the parasites were in an unsynchronized or synchronized state of growth , respectively .


Treatment of human erythrocytes with 10 microM sodium orthovanadate ( NaOV ) , an inhibitor of plasma membrane Ca-ATPase and phosphotyrosine phosphatase , decreased parasitemia by 30 % .

Treatment of <cell_type>human erythrocytes</cell_type> with 10 microM sodium orthovanadate ( NaOV ) , an inhibitor of <protein>plasma membrane Ca-ATPase</protein> and <protein>phosphotyrosine phosphatase</protein> , decreased parasitemia by 30 % .


Co-treatment of RBCs with TCDD and NaOV completely blocked the TCDD-induced increase in parasitemia .

Co-treatment of <cell_type>RBCs</cell_type> with TCDD and NaOV completely blocked the TCDD-induced increase in parasitemia .


Because erythrocytes are anucleated , these results are discussed as evidence for biochemical changes by TCDD without requiring the activation of gene products .

Because <cell_type>erythrocytes</cell_type> are anucleated , these results are discussed as evidence for biochemical changes by TCDD without requiring the activation of <protein>gene products</protein> .


Evidence for a trans-acting activator function regulating the expression of the human CD5 antigen .

Evidence for a <protein>trans-acting activator</protein> function regulating the expression of the <protein>human CD5 antigen</protein> .


Interspecies somatic cell hybrids were generated by fusing the mouse T-lymphoma cell line , BW5147 , with normal human T lymphocytes at different stages of differentiation .

Interspecies <cell_line>somatic cell hybrids</cell_line> were generated by fusing the <cell_line>mouse T-lymphoma cell line</cell_line> , <cell_line>BW5147</cell_line> , with <cell_type>normal human T lymphocytes</cell_type> at different stages of differentiation .


Thymocytes , activated peripheral T lymphocytes , or an activated T-cell clone were used as human partners , respectively , in three independent fusions .

<cell_type>Thymocytes</cell_type> , <cell_type>activated peripheral T lymphocytes</cell_type> , or an <cell_line>activated T-cell clone</cell_line> were used as human partners , respectively , in three independent fusions .


Irrespective of the human cell partner used for fusion , a certain number of hybrids lost CD5 surface expression over a period of time in culture .

Irrespective of the human cell partner used for fusion , a certain number of <cell_line>hybrids</cell_line> lost <protein>CD5</protein> surface expression over a period of time in culture .


Analysis at the phenotype and genetic level showed that lack of CD5 expression was due neither to segregation of human autosome 11 , on which the CD5 gene has been mapped , nor to deletion of the CD5 structural gene .

Analysis at the phenotype and genetic level showed that lack of <protein>CD5</protein> expression was due neither to segregation of <dna>human autosome 11</dna> , on which the <dna>CD5 gene</dna> has been mapped , nor to deletion of the <dna>CD5 structural gene</dna> .


Furthermore , loss of CD5 surface expression correlated with the absence of specific mRNA .

Furthermore , loss of <protein>CD5</protein> surface expression correlated with the absence of specific <rna>mRNA</rna> .


Since these hybrids preferentially segregate human chromosomes , these results indicate the existence of a non-syntenic trans-active locus , or loci , positively controlling the expression of the human CD5 gene .

Since these hybrids preferentially segregate human chromosomes , these results indicate the existence of a <dna>non-syntenic trans-active locus</dna> , or loci , positively controlling the expression of the <dna>human CD5 gene</dna> .


Induction of the CD11b gene during activation of the monocytic cell line U937 requires a novel nuclear factor MS-2 [ published erratum appears in J Immunol 1999 Jul 15 ; 163 ( 2 ) : 1091 ]

Induction of the <dna>CD11b gene</dna> during activation of the <cell_line>monocytic cell line U937</cell_line> requires a novel <protein>nuclear factor</protein> <protein>MS-2</protein> [ published erratum appears in J Immunol 1999 Jul 15 ; 163 ( 2 ) : 1091 ]


The differentiation of myeloid precursors into mature myelomonocytic cells is characterized by the induction of the gene encoding the beta2 integrin CD11b .

The differentiation of <cell_type>myeloid precursors</cell_type> into mature <cell_type>myelomonocytic cells</cell_type> is characterized by the induction of the gene encoding the <protein>beta2 integrin</protein> <protein>CD11b</protein> .


The transcription factors Sp1 and PU.1 prime the CD11b promoter , but the nature of the factors responsible for its inducible expression are unknown .

The <protein>transcription factors</protein> <protein>Sp1</protein> and <protein>PU.1 prime</protein> the <dna>CD11b promoter</dna> , but the nature of the factors responsible for its inducible expression are unknown .


In addition to the CD11b gene , the homologous genes encoding CD11a and CD11c also exhibit inducible expression during myeloid differentiation .

In addition to the <dna>CD11b gene</dna> , the homologous genes encoding <protein>CD11a</protein> and <protein>CD11c</protein> also exhibit inducible expression during myeloid differentiation .


Therefore , we compared the nucleotide sequences of the CD11a , CD11b , and CD11c gene promoters to identify common elements that might contribute to inducible expression .

Therefore , we compared the <dna>nucleotide sequences</dna> of the <dna>CD11a , CD11b , and CD11c gene promoters</dna> to identify common elements that might contribute to inducible expression .


This analysis identified one such element repeated four times within the CD11b promoter .

This analysis identified one such element repeated four times within the <dna>CD11b promoter</dna> .


Mutation of these elements indicated that two , MS-2beta and MS-2gamma , are critical to the induction of the CD11b gene during differentiation of the pro-monocytic cell line U937 .

Mutation of these elements indicated that two , <protein>MS-2beta</protein> and <protein>MS-2gamma</protein> , are critical to the induction of the <dna>CD11b gene</dna> during differentiation of the <cell_line>pro-monocytic cell line U937</cell_line> .


Electrophoretic mobility shift assays indicate that MS-2beta and MS-2gamma interact with nuclear factors that are induced during U937 differentiation .

Electrophoretic mobility shift assays indicate that <protein>MS-2beta</protein> and <protein>MS-2gamma</protein> interact with <protein>nuclear factors</protein> that are induced during <cell_line>U937</cell_line> differentiation .


These factors are detected at the time the CD11b promoter is activated .

These factors are detected at the time the <dna>CD11b promoter</dna> is activated .


The molecular mass of these factors is approximately 28 kDa , and their DNA binding characteristics are indistinguishable from those of the novel nuclear factor MS-2 .

The molecular mass of these factors is approximately 28 kDa , and their DNA binding characteristics are indistinguishable from those of the novel <protein>nuclear factor</protein> <protein>MS-2</protein> .


Taken together , our data indicate that MS-2 mediates induction of the CD11b gene as cells of the monocytic lineage mature .

Taken together , our data indicate that <protein>MS-2</protein> mediates induction of the <dna>CD11b gene</dna> as cells of the monocytic lineage mature .


The presence of multiple potential binding sites for MS-2 in the promoter regions of a wide range of genes expressed in mature myeloid cells suggests this factor plays a general role in myeloid differentiation .

The presence of multiple potential binding sites for <protein>MS-2</protein> in the promoter regions of a wide range of genes expressed in <cell_type>mature myeloid cells</cell_type> suggests this factor plays a general role in myeloid differentiation .


Acetylsalicylic acid and sodium salicylate inhibit LPS-induced NF-kappa B/c-Rel nuclear translocation , and synthesis of tissue factor ( TF ) and tumor necrosis factor alfa ( TNF-alpha ) in human monocytes .

Acetylsalicylic acid and sodium salicylate inhibit LPS-induced <protein>NF-kappa B/c-Rel</protein> nuclear translocation , and synthesis of <protein>tissue factor</protein> ( <protein>TF</protein> ) and <protein>tumor necrosis factor alfa</protein> ( <protein>TNF-alpha</protein> ) in <cell_type>human monocytes</cell_type> .


We have investigated the effects of acetylsalicylic acid and sodium salicylate on the LPS-induced synthesis of the pro-coagulant protein tissue factor ( TF ) and the pro-inflammatory protein tumor necrosis factor-alpha ( TNF-alpha ) , as well as the prostaglandin PGE2 in human monocytes .

We have investigated the effects of acetylsalicylic acid and sodium salicylate on the LPS-induced synthesis of the pro-coagulant protein tissue factor ( TF ) and the pro-inflammatory protein tumor necrosis factor-alpha ( <protein>TNF-alpha</protein> ) , as well as the <protein>prostaglandin PGE2</protein> in <cell_type>human monocytes</cell_type> .


Both drugs dose-dependently inhibited LPS-induced TF and TNF-alpha synthesis at the mRNA and the protein level , and reduced PGE2 production .

Both drugs dose-dependently inhibited <protein>LPS-induced TF</protein> and <protein>TNF-alpha</protein> synthesis at the <rna>mRNA</rna> and the protein level , and reduced <protein>PGE2</protein> production .


As evidenced by electro mobility shift assay ( EMSA ) and the use of a NF-kappa B prototypic probe , these drugs probably exert their inhibitory effects by interference with the nuclear translocation of NF-kappa B/c-Rel proteins .

As evidenced by electro mobility shift assay ( EMSA ) and the use of a <dna>NF-kappa B prototypic probe</dna> , these drugs probably exert their inhibitory effects by interference with the nuclear translocation of <protein>NF-kappa B/c-Rel proteins</protein> .


These data may expand the understanding of the anti-thrombotic and anti-inflammatory effects of these drugs when activation of monocytes occurs .

These data may expand the understanding of the anti-thrombotic and anti-inflammatory effects of these drugs when activation of <cell_type>monocytes</cell_type> occurs .


Interferon augments PML and PML/RAR alpha expression in normal myeloid and acute promyelocytic cells and cooperates with all-trans retinoic acid to induce maturation of a retinoid-resistant promyelocytic cell line .

Interferon augments <protein>PML</protein> and <protein>PML/RAR alpha</protein> expression in normal <cell_type>myeloid</cell_type> and <cell_type>acute promyelocytic cells</cell_type> and cooperates with all-trans retinoic acid to induce maturation of a <cell_line>retinoid-resistant promyelocytic cell line</cell_line> .


The PML gene is fused to the retinoic acid receptor alpha gene ( RAR alpha ) in the acute promyelocytic leukemia ( APL ) 15 ; 17 translocation .

The <dna>PML gene</dna> is fused to the <dna>retinoic acid receptor alpha gene</dna> ( <dna>RAR alpha</dna> ) in the acute promyelocytic leukemia ( APL ) 15 ; 17 translocation .


PML is expressed in diverse tissues and cell lines and localized in the nucleus with a typical speckled pattern .

<protein>PML</protein> is expressed in diverse tissues and cell lines and localized in the nucleus with a typical speckled pattern .


In the bone marrow , it is preferentially expressed in myeloid cells .

In the bone marrow , it is preferentially expressed in <cell_type>myeloid cells</cell_type> .


PML appears to be transcriptionally regulated by class I and II interferons , which raises the possibility that interferons modulate the function and growth and differentiation potential of normal myeloid cells and precursors by activating PML -dependent pathways .

<protein>PML</protein> appears to be transcriptionally regulated by <protein>class I and II interferons</protein> , which raises the possibility that interferons modulate the function and growth and differentiation potential of normal <cell_type>myeloid cells</cell_type> and precursors by activating <protein>PML</protein> -dependent pathways .


Similarly , interferons could act on APL cells , alone or in combination with all-trans retinoic acid ( RA ) , especially if the PML/RAR alpha fusion transcript that results from the t ( 15 ; 17 ) is induced by interferon .

Similarly , interferons could act on <cell_type>APL cells</cell_type> , alone or in combination with all-trans retinoic acid ( RA ) , especially if the <rna>PML/RAR alpha fusion transcript</rna> that results from the <dna>t ( 15 ; 17 )</dna> is induced by <protein>interferon</protein> .


We report here that PML is expressed at low levels or not expressed in normal circulating human monocytes , lymphocytes , and polymorphonucleate cells , but is markedly induced by interferon ; that PML and PML/RAR alpha expression is augmented by interferon in the NB4 APL cell line , which carries the t ( 15 ; 17 ) , and in APL blasts from patients ; that interferon inhibits growth and survival of NB4 APL cells in cooperation with RA ; that interferons alone have minimal maturation effect on NB4 cells ; and , finally , that interferon gamma , but not alpha or beta , induces maturation and growth suppression of NB4 cells with de novo retinoid resistance , and partially restores RA response .

We report here that <protein>PML</protein> is expressed at low levels or not expressed in normal circulating <cell_type>human monocytes</cell_type> , <cell_type>lymphocytes</cell_type> , and <cell_type>polymorphonucleate cells</cell_type> , but is markedly induced by <protein>interferon</protein> ; that <protein>PML</protein> and <protein>PML/RAR alpha</protein> expression is augmented by <protein>interferon</protein> in the <cell_line>NB4 APL cell line</cell_line> , which carries the <dna>t ( 15 ; 17 )</dna> , and in <cell_type>APL blasts</cell_type> from patients ; that <protein>interferon</protein> inhibits growth and survival of NB4 <cell_type>APL cells</cell_type> in cooperation with RA ; that interferons alone have minimal maturation effect on <cell_line>NB4 cells</cell_line> ; and , finally , that <protein>interferon gamma , but not alpha or beta</protein> , induces maturation and growth suppression of <cell_line>NB4 cells</cell_line> with de novo retinoid resistance , and partially restores RA response .


Effects of Ara-C on neutral sphingomyelinase and mitogen- and stress- activated protein kinases in T-lymphocyte cell lines .

Effects of Ara-C on <protein>neutral sphingomyelinase</protein> and <protein>mitogen- and stress- activated protein kinases</protein> in <cell_line>T-lymphocyte cell lines</cell_line> .


Neutral sphingomyelinase ( SMase ) can be activated by extracellular signals to produce ceramide , which may affect mitogen-activated protein kinase ( MAPK ) activities .

<protein>Neutral sphingomyelinase</protein> ( <protein>SMase</protein> ) can be activated by extracellular signals to produce ceramide , which may affect <protein>mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) activities .


Neutral SMase activity was assessed in membranes from Jurkat , a human T-cell line , and EL4 , a murine T-cell line .

Neutral <protein>SMase</protein> activity was assessed in membranes from <cell_line>Jurkat</cell_line> , a <cell_line>human T-cell line</cell_line> , and <cell_line>EL4</cell_line> , a <cell_line>murine T-cell line</cell_line> .


Ara-C activated SMase with 10 minutes in both Jurkat and EL4 cells , while phorbol ester ( PMA ) had no effect .

Ara-C activated <protein>SMase</protein> with 10 minutes in both Jurkat and <cell_line>EL4 cells</cell_line> , while phorbol ester ( PMA ) had no effect .