In driving T cell proliferation , IL-2 stimulates a new program of gene expression that includes proliferating cell nuclear antigen ( PCNA ) , a requisite processivity factor for DNA polymerase delta .

In driving T cell proliferation , <protein>IL-2</protein> stimulates a new program of gene expression that includes <protein>proliferating cell nuclear antigen</protein> ( <protein>PCNA</protein> ) , a requisite processivity factor for <protein>DNA polymerase delta</protein> .


PCNA transcription is regulated in part through tandem CRE sequences in the promoter and CRE binding proteins ; IL-2 stimulates CREB phosphorylation in the resting cloned T lymphocyte , L2 .

<protein>PCNA</protein> transcription is regulated in part through tandem <dna>CRE sequences</dna> in the <protein>promoter and CRE binding proteins</protein> ; <protein>IL-2</protein> stimulates CREB phosphorylation in the <cell_line>resting cloned T lymphocyte</cell_line> , <cell_line>L2</cell_line> .


After culturing L2 cells for greater than 91 days , we consistently isolate a stable variant that exhibits constitutive CREB phosphorylation .

After culturing <cell_line>L2 cells</cell_line> for greater than 91 days , we consistently isolate a stable variant that exhibits constitutive CREB phosphorylation .


L2 and L2 variant cells were tested for IL-2 responsiveness and rapamycin sensitivity with respect to specific kinase activity , PCNA expression and proliferation .

<cell_line>L2 and L2 variant cells</cell_line> were tested for <protein>IL-2</protein> responsiveness and rapamycin sensitivity with respect to specific kinase activity , PCNA expression and proliferation .


In L2 cells , IL-2 stimulated and rapamycin inhibited the following : cAMP-independent CREB kinase activity , PCNA expression and proliferation .

In <cell_line>L2 cells</cell_line> , <protein>IL-2</protein> stimulated and rapamycin inhibited the following : cAMP-independent <protein>CREB kinase</protein> activity , PCNA expression and proliferation .


In L2 variant cells , CREB kinase activity was constitutively high ; IL-2 stimulated and rapamycin blocked PCNA expression and proliferation .

In <cell_line>L2 variant cells</cell_line> , <protein>CREB kinase</protein> activity was constitutively high ; <protein>IL-2</protein> stimulated and rapamycin blocked PCNA expression and proliferation .


These results indicate that IL-2 induces a rapamycin-sensitive , cAMP-independent CREB kinase activity in L2 cells .

These results indicate that <protein>IL-2</protein> induces a rapamycin-sensitive , cAMP-independent <protein>CREB kinase</protein> activity in <cell_line>L2 cells</cell_line> .


However , phosphorylation of CREB alone is not sufficient to drive PCNA expression and L2 cell proliferation in the absence of IL-2 .

However , phosphorylation of <protein>CREB</protein> alone is not sufficient to drive <protein>PCNA</protein> expression and L2 cell proliferation in the absence of <protein>IL-2</protein> .


Serotonin derivative , N- ( p-coumaroyl ) serotonin , inhibits the production of TNF-alpha , IL-1alpha , IL-1beta , and IL-6 by endotoxin-stimulated human blood monocytes .

Serotonin derivative , N- ( p-coumaroyl ) serotonin , inhibits the production of <protein>TNF-alpha</protein> , <protein>IL-1alpha</protein> , <protein>IL-1beta</protein> , and <protein>IL-6</protein> by <cell_type>endotoxin-stimulated human blood monocytes</cell_type> .


We have reported that N- ( p-coumaroyl ) serotonin ( CS ) and its derivatives with antioxidative activity are present in safflower seeds .


As reactive oxygen species ( ROS ) are implicated in the signaling of lipopolysaccharide ( LPS ) , we examined whether CS has a suppressive effect on inflammatory cytokine generation from human monocyte s in vitro .

As reactive oxygen species ( ROS ) are implicated in the signaling of lipopolysaccharide ( LPS ) , we examined whether CS has a suppressive effect on <protein>inflammatory cytokine</protein> generation from <cell_type>human monocyte</cell_type> s in vitro .


CS at 50-200 microM reduced tumor necrosis factor ( TNF ) , interleukin-1 ( IL-1 ) , and IL-6 activities in the culture supernatants from LPS-stimulated human blood monocytes without cytotoxicity .

CS at 50-200 microM reduced <protein>tumor necrosis factor</protein> ( <protein>TNF</protein> ) , <protein>interleukin-1</protein> ( <protein>IL-1</protein> ) , and <protein>IL-6</protein> activities in the culture supernatants from <cell_line>LPS-stimulated human blood monocytes</cell_line> without cytotoxicity .


ELISA assay revealed that the production of TNF-alpha , IL-1alpha , IL-1beta , and IL-6 was inhibited by CS .

ELISA assay revealed that the production of <protein>TNF-alpha</protein> , <protein>IL-1alpha</protein> , <protein>IL-1beta</protein> , and <protein>IL-6</protein> was inhibited by CS .


Northern blot analysis showed that LPS-induced expression of these cytokine mRNA in monocytes was suppressed by CS .

Northern blot analysis showed that LPS-induced expression of these <rna>cytokine mRNA</rna> in <cell_type>monocytes</cell_type> was suppressed by CS .


NF-kappaB activation was also inhibited by CS .


These findings indicate that CS has a suppressive effect on proinflammatory cytokine production from monocytes , and this effect is based in part on the suppression of cytokine mRNA expression through inhibition of NF-kappaB activation .

These findings indicate that CS has a suppressive effect on proinflammatory cytokine production from <cell_type>monocytes</cell_type> , and this effect is based in part on the suppression of <rna>cytokine mRNA</rna> expression through inhibition of <protein>NF-kappaB</protein> activation .


Elevated expression of differentiation inhibitory factor nm23 mRNA in monoblastic crisis of a patient with chronic myelogenous leukemia .

Elevated expression of <rna>differentiation inhibitory factor nm23 mRNA</rna> in monoblastic crisis of a patient with chronic myelogenous leukemia .


Differentiation inhibitory factor nm23 gene has been found to be expressed in high quantities in acute myelogenous leukemia ( AML ) , especially in acute monocytic leukemia ( AML-M5 ) and is suggested as a new prognostic factor in AML-M5 .

<protein>Differentiation inhibitory factor</protein> <dna>nm23 gene</dna> has been found to be expressed in high quantities in acute myelogenous leukemia ( AML ) , especially in acute monocytic leukemia ( AML-M5 ) and is suggested as a new prognostic factor in AML-M5 .


We report an example of elevated expression of nm23 mRNA in a patient with chronic myelogenous leukemia ( CML ) who developed monoblastic crisis .

We report an example of elevated expression of <rna>nm23 mRNA</rna> in a patient with chronic myelogenous leukemia ( CML ) who developed monoblastic crisis .


Relative levels of nm23-H1 and -H2 mRNA extracted from the patient 's peripheral blood mononuclear cells and bone marrow mononuclear cells were measured by quantitative reverse transcriptase polymerase chain reaction .

Relative levels of <rna>nm23-H1 and -H2 mRNA</rna> extracted from the patient 's <cell_type>peripheral blood mononuclear cells</cell_type> and <cell_type>bone marrow mononuclear cells</cell_type> were measured by quantitative reverse transcriptase polymerase chain reaction .


The level of nm23-H1 mRNA in CML cells at the chronic phase was as high as that in bone marrow cells from healthy volunteers .

The level of <rna>nm23-H1 mRNA</rna> in <cell_line>CML cells</cell_line> at the chronic phase was as high as that in <cell_type>bone marrow cells</cell_type> from healthy volunteers .


The mRNA level of nm23-H2 was slightly below the normal level .

The mRNA level of <protein>nm23-H2</protein> was slightly below the normal level .


At blastic crisis , however , expression of both nm23-H1 and -H2 mRNA was elevated to about three to nine times of that at the chronic phase .

At blastic crisis , however , expression of both <rna>nm23-H1 and -H2 mRNA</rna> was elevated to about three to nine times of that at the chronic phase .


Proliferated blastic cells were positive for non-specific esterase , and the serum lysozyme level was elevated and diagnosed as monoblastic crisis .

<cell_type>Proliferated blastic cells</cell_type> were positive for <protein>non-specific esterase</protein> , and the serum lysozyme level was elevated and diagnosed as monoblastic crisis .


The patient received combined chemotherapy but response was partial .


These findings are compatible with our previous report that nm23 gene is overexpressed in monocytic leukemia .

These findings are compatible with our previous report that <dna>nm23 gene</dna> is overexpressed in monocytic leukemia .


Increased transcription decreases the spontaneous mutation rate at the thymidine kinase locus in human cells .

Increased transcription decreases the spontaneous mutation rate at the <dna>thymidine kinase locus</dna> in <cell_type>human cells</cell_type> .


Transcription increases DNA repair efficiency and modulates the distribution of certain types of DNA damage .


Furthermore , increased transcription level stimulates spontaneous mutation rate in yeast .


We explored whether transcription level affects spontaneous mutation rate in human cells .

We explored whether transcription level affects spontaneous mutation rate in <cell_type>human cells</cell_type> .


We first developed two thymidine kinase ( tk ) inducible human cell lines using the Gal4-Estrogen receptor system .

We first developed two <cell_line>thymidine kinase ( tk ) inducible human cell lines</cell_line> using the Gal4-Estrogen receptor system .


In our TK6i-G3 and G9 tk heterozygous cell lines , the active tk allele is linked to an inducible promoter element .

In our <cell_line>TK6i-G3 and G9 tk heterozygous cell lines</cell_line> , the active <dna>tk allele</dna> is linked to an inducible <dna>promoter element</dna> .


Tk mRNA is induced following treatment with estrogen .

<rna>Tk mRNA</rna> is induced following treatment with estrogen .


Spontaneous mutation rate was significantly decreased in human cell lines after induction in contrast to the report in yeast .

Spontaneous mutation rate was significantly decreased in <cell_line>human cell lines</cell_line> after induction in contrast to the report in yeast .


Thus , humans may have evolved different or additional mechanisms to deal with transcription related spontaneous mutagenesis .


Copyright 1998 Elsevier Science B.V .


All rights reserved .


Mutation of BCL-6 gene in normal B cells by the process of somatic hypermutation of Ig genes .

Mutation of <dna>BCL-6 gene</dna> in normal <cell_type>B cells</cell_type> by the process of somatic hypermutation of <dna>Ig genes</dna> .


Immunoglobulin ( Ig ) genes are hypermutated in B lymphocytes that are the precursors to memory B cells .

<dna>Immunoglobulin ( Ig ) genes</dna> are hypermutated in <cell_type>B lymphocytes</cell_type> that are the precursors to <cell_type>memory B cells</cell_type> .


The mutations are linked to transcription initiation , but non-Ig promoters are permissible for the mutation process ; thus , other genes expressed in mutating B cells may also be subject to somatic hypermutation .

The mutations are linked to transcription initiation , but <dna>non-Ig promoters</dna> are permissible for the mutation process ; thus , other genes expressed in mutating <cell_type>B cells</cell_type> may also be subject to somatic hypermutation .


Significant mutations were not observed in c-MYC , S14 , or alpha-fetoprotein ( AFP ) genes , but BCL-6 was highly mutated in a large proportion of memory B cells of normal individuals .

Significant mutations were not observed in <dna>c-MYC , S14 , or alpha-fetoprotein ( AFP ) genes</dna> , but <protein>BCL-6</protein> was highly mutated in a large proportion of <cell_type>memory B cells</cell_type> of normal individuals .


The mutation pattern was similar to that of Ig genes .

The mutation pattern was similar to that of <dna>Ig genes</dna> .


CD28-mediated activation in CD45RA+ and CD45RO+ T cells : enhanced levels of reactive oxygen intermediates and c-Rel nuclear translocation in CD45RA+ cells .

CD28-mediated activation in <cell_type>CD45RA+ and CD45RO+ T cells</cell_type> : enhanced levels of reactive oxygen intermediates and c-Rel nuclear translocation in <cell_type>CD45RA+ cells</cell_type> .


We have analyzed the effect of complete T cell activation ( anti-CD3 plus anti-CD28 ) on the activation of NF-kappaB in CD45RA+ ( naive ) and CD45RO+ ( memory/effector ) T cells .

We have analyzed the effect of complete T cell activation ( anti-CD3 plus anti-CD28 ) on the activation of <protein>NF-kappaB</protein> in <cell_type>CD45RA+ ( naive ) and CD45RO+ ( memory/effector ) T cells</cell_type> .


Long exposure ( 24 h ) induced stronger NF-kappaB DNA binding in CD45RA+ cells than in CD45RO+ cells .

Long exposure ( 24 h ) induced stronger <protein>NF-kappaB</protein> DNA binding in <cell_type>CD45RA+ cells</cell_type> than in <cell_type>CD45RO+ cells</cell_type> .


Analysis of the nuclear c-Rel protein indicated that after anti-CD3+anti-CD28 stimulation the level of c-Rel was higher in CD45RA+ cells .

Analysis of the <protein>nuclear c-Rel protein</protein> indicated that after anti-CD3+anti-CD28 stimulation the level of <protein>c-Rel</protein> was higher in <cell_type>CD45RA+ cells</cell_type> .


Analysis of the cytoplasmic inhibitor IkappaBalpha indicated that anti-CD3+anti-CD28 stimulation induced a long-lasting degradation in CD45RA+ cells but in CD45RO+ cells the degradation process was more rapid .

Analysis of the <protein>cytoplasmic inhibitor</protein> <protein>IkappaBalpha</protein> indicated that anti-CD3+anti-CD28 stimulation induced a long-lasting degradation in <cell_type>CD45RA+ cells</cell_type> but in <cell_type>CD45RO+ cells</cell_type> the degradation process was more rapid .


Because the CD28 costimulus is known to induce the production of reactive oxygen intermediates ( ROIs ) , the intracellular ROI levels in CD45RA+ and CD45RO+ cells were compared by flow cytometry .

Because the <protein>CD28</protein> costimulus is known to induce the production of reactive oxygen intermediates ( ROIs ) , the intracellular ROI levels in <cell_type>CD45RA+ and CD45RO+ cells</cell_type> were compared by flow cytometry .


ROIs were produced in both cell types , but more strongly in CD45RA+ cells .

ROIs were produced in both cell types , but more strongly in <cell_type>CD45RA+ cells</cell_type> .


The data presented in this study further emphasize the differences between CD45RA+ and CD45RO+ T lymphocytes in ROI-dependent signaling pathways .

The data presented in this study further emphasize the differences between <cell_type>CD45RA+ and CD45RO+ T lymphocytes</cell_type> in ROI-dependent signaling pathways .


Non-Hodgkin 's lymphoma involving bilateral breasts [ see comments ]


We describe here two cases of diffuse large cell type non-Hodgkin 's lymphoma affecting the bilateral breasts .


The contralateral tumor in one case appeared 17 months after the first mastectomy , whereas the bilateral tumors occurred concurrently in the other patient who was pregnant and showed widespread dissemination at initial presentation .


Lymphoma cells from both cases showed the mature B-cell immunophenotype and had rearrangements of the BCL6 gene .

<cell_type>Lymphoma cells</cell_type> from both cases showed the mature B-cell immunophenotype and had rearrangements of the <dna>BCL6 gene</dna> .


Both patients developed progressive disease despite chemo-radiotherapy and died of leukemic manifestations .


There were no apparent pathological features of lymphomas of mucosa-associated lymphoid tissue origin


Biochemical characterization of MIP-1 alpha nuclear protein .

Biochemical characterization of <protein>MIP-1 alpha nuclear protein</protein> .


A family of hematopoietic specific transcription factors , MIP-1 alpha nuclear protein ( MNP ) family , has recently been identified .

A family of <protein>hematopoietic specific transcription factors</protein> , <protein>MIP-1 alpha nuclear protein ( MNP ) family</protein> , has recently been identified .


They are intimately involved in regulating the transcription of the huMIP-1 alpha gene in monocytes , T-cells , and transformed B-cells .

They are intimately involved in regulating the transcription of the <dna>huMIP-1 alpha gene</dna> in <cell_type>monocytes</cell_type> , <cell_type>T-cells</cell_type> , and <cell_type>transformed B-cells</cell_type> .


One member of the family ( MNP-1 ) is essential for promoter activity in monocytes and B-cells , while another ( MNP-2 ) is required for full promotor activity in T-cells .

One member of the family ( <protein>MNP-1</protein> ) is essential for promoter activity in <cell_type>monocytes</cell_type> and <cell_type>B-cells</cell_type> , while another ( <protein>MNP-2</protein> ) is required for full promotor activity in <cell_type>T-cells</cell_type> .


A third member of the family ( MNP-3 ) is expressed in PMA induced HL60 cells and probably has a role in monocyte differentiation .

A third member of the family ( <protein>MNP-3</protein> ) is expressed in <cell_line>PMA induced HL60 cells</cell_line> and probably has a role in monocyte differentiation .


In this communication we demonstrate by two techniques that MNP-1 and MNP-2 are distinct but related factors , and we present further evidence to show that MNP-1 acts as a heterodimer .

In this communication we demonstrate by two techniques that <protein>MNP-1</protein> and <protein>MNP-2</protein> are distinct but related factors , and we present further evidence to show that <protein>MNP-1</protein> acts as a <protein>heterodimer</protein> .


Bcl-3 expression and nuclear translocation are induced by granulocyte-macrophage colony-stimulating factor and erythropoietin in proliferating human erythroid precursors .

<protein>Bcl-3</protein> expression and nuclear translocation are induced by <protein>granulocyte-macrophage colony-stimulating factor</protein> and <protein>erythropoietin</protein> in <cell_type>proliferating human erythroid precursors</cell_type> .


Bcl-3 is a proto-oncogene involved in the chromosomal translocation t ( 14 ; 19 ) found in some patients with chronic lymphocytic leukemia .

<protein>Bcl-3</protein> is a <dna>proto-oncogene</dna> involved in the chromosomal translocation <dna>t ( 14 ; 19 )</dna> found in some patients with chronic lymphocytic leukemia .


It shares structural similarities with and is a member of the IkappaB family of proteins .

It shares structural similarities with and is a member of the <protein>IkappaB family</protein> of proteins .


In this report , involvement of Bcl-3 in hematopoietic growth factor-stimulated erythroid proliferation and differentiation was examined .

In this report , involvement of <protein>Bcl-3</protein> in hematopoietic growth factor-stimulated erythroid proliferation and differentiation was examined .


In TF-1 cells , an erythroleukemia cell line , granulocyte-macrophage colony-stimulating factor ( GM-CSF ) and erythropoietin ( Epo ) greatly enhanced Bcl-3 expression at both the protein and mRNA levels in association with stimulation of proliferation .

In <cell_line>TF-1 cells</cell_line> , an <cell_line>erythroleukemia cell line</cell_line> , <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) and <protein>erythropoietin</protein> ( <protein>Epo</protein> ) greatly enhanced <protein>Bcl-3</protein> expression at both the protein and mRNA levels in association with stimulation of proliferation .


Bcl-3 protein was also highly expressed in early burst-forming unit-erythroid ( BFU-E ) -derived erythroid precursors ( day 7 ) and decreased during maturation ( days 10 and 14 ) , suggesting that Bcl-3 is involved in normal erythroid proliferation .

<protein>Bcl-3</protein> protein was also highly expressed in <cell_type>early burst-forming unit-erythroid ( BFU-E ) -derived erythroid precursors</cell_type> ( day 7 ) and decreased during maturation ( days 10 and 14 ) , suggesting that <protein>Bcl-3</protein> is involved in normal erythroid proliferation .


In these hematopoietic cells , Bcl-3 was hyperphosphorylated .

In these <cell_type>hematopoietic cells</cell_type> , <protein>Bcl-3</protein> was hyperphosphorylated .


GM-CSF and Epo modulated the subcellular localization of Bcl-3 .

<protein>GM-CSF</protein> and <protein>Epo</protein> modulated the subcellular localization of <protein>Bcl-3</protein> .


Upon stimulation of TF-1 cells with GM-CSF or Epo , the nuclear translocation of Bcl-3 was dramatically enhanced .

Upon stimulation of <cell_line>TF-1 cells</cell_line> with <protein>GM-CSF</protein> or <protein>Epo</protein> , the nuclear translocation of <protein>Bcl-3</protein> was dramatically enhanced .


Overexpression of Bcl-3 in TF-1 cells by transient transfection along with the NF-kappaB factors p50 or p52 resulted in significant induction of an human immunodeficiency virus-type 1 ( HIV-1 ) kappaB-TATA-luceriferase reporter plasmid , demonstrating that Bcl-3 has a positive role in transactivation of kappaB-containing genes in erythroid cells .

Overexpression of <protein>Bcl-3</protein> in <cell_line>TF-1 cells</cell_line> by transient transfection along with the <protein>NF-kappaB factors p50 or p52</protein> resulted in significant induction of an <dna>human immunodeficiency virus-type 1 ( HIV-1 ) kappaB-TATA-luceriferase reporter plasmid</dna> , demonstrating that <protein>Bcl-3</protein> has a positive role in transactivation of <dna>kappaB-containing genes</dna> in <cell_type>erythroid cells</cell_type> .


Stimulation with GM-CSF enhanced c-myb mRNA expression in these cells .

Stimulation with <protein>GM-CSF</protein> enhanced <rna>c-myb mRNA</rna> expression in these cells .


Bcl-3 in nuclear extracts of TF-1 cells bound to a kappaB enhancer in the c-myb promoter together with NF-kappaB2/p52 and this binding activity was enhanced by GM-CSF stimulation .

<protein>Bcl-3</protein> in nuclear extracts of <cell_line>TF-1 cells</cell_line> bound to a <dna>kappaB enhancer</dna> in the <dna>c-myb promoter</dna> together with <protein>NF-kappaB2/p52</protein> and this binding activity was enhanced by <protein>GM-CSF</protein> stimulation .


Furthermore , cotransfection of Bcl-3 with p52 or p50 in TF-1 cells resulted in significant activation of a c-myb kappaB-TATA-luceriferase reporter plasmid .

Furthermore , cotransfection of <protein>Bcl-3</protein> with <protein>p52</protein> or <protein>p50</protein> in <cell_line>TF-1 cells</cell_line> resulted in significant activation of a <dna>c-myb kappaB-TATA-luceriferase reporter plasmid</dna> .


These findings suggest that Bcl-3 may participate in the transcriptional regulation of certain kappaB-containing genes involved in hematopoiesis , including c-myb .

These findings suggest that <protein>Bcl-3</protein> may participate in the transcriptional regulation of certain <dna>kappaB-containing genes</dna> involved in hematopoiesis , including <dna>c-myb</dna> .


Copyright 1998 by The American Society of Hematology .


5-Lipoxygenase compartmentalization in granulocytic cells is modulated by an internal bipartite nuclear localizing sequence and nuclear factor kappa B complex formation .

<protein>5-Lipoxygenase</protein> compartmentalization in granulocytic cells is modulated by an <protein>internal bipartite nuclear localizing sequence</protein> and <protein>nuclear factor kappa B complex</protein> formation .


A region of basic amino acids spanning residues 639-656 in the human 5-lipoxygenase sequence resembles a consensus bipartite nuclear localizing sequence .

A region of basic amino acids spanning <protein>residues 639-656</protein> in the <protein>human 5-lipoxygenase sequence</protein> resembles a <protein>consensus bipartite nuclear localizing sequence</protein> .


A synthetic peptide consisting of the Kaposi fibroblast growth factor signal sequence fused to the 5-lipoxygenase639-656 bipartite nuclear localizing sequence has a prominent inhibitory effect on 5-lipoxygenase catalysis in granulocytic HL-60 cells activated by calcium ionophor A23187 .

A synthetic peptide consisting of the <protein>Kaposi fibroblast growth factor signal sequence</protein> fused to the <protein>5-lipoxygenase639-656 bipartite nuclear localizing sequence</protein> has a prominent inhibitory effect on <protein>5-lipoxygenase</protein> catalysis in granulocytic <cell_line>HL-60 cells</cell_line> activated by calcium ionophor A23187 .


Recombinant 5-lipoxygenase was not affected by the peptide .

Recombinant <protein>5-lipoxygenase</protein> was not affected by the peptide .


The peptide also inhibited redistribution of 5-lipoxygenase from the cytosol to the nuclear membrane of HL-60 cells stimulated by A23187 .

The peptide also inhibited redistribution of <protein>5-lipoxygenase</protein> from the cytosol to the nuclear membrane of <cell_line>HL-60 cells</cell_line> stimulated by A23187 .


5-Lipoxygenase protein was detected in nuclear factor kappaB ( NF-kappaB ) p65 subunit immunoprecipitate fractions prepared from HL-60 cell lysates .

<protein>5-Lipoxygenase protein</protein> was detected in <protein>nuclear factor kappaB ( NF-kappaB ) p65 subunit</protein> immunoprecipitate fractions prepared from <cell_line>HL-60 cell</cell_line> lysates .


The amount of 5-lipoxygenase protein coimmunoprecipitated by NF-kappaB antiserum was increased following A23187 stimulation .

The amount of <protein>5-lipoxygenase protein</protein> coimmunoprecipitated by NF-kappaB antiserum was increased following A23187 stimulation .


In cells treated with agents that block 5-lipoxygenase translocation to the nucleus , 5-lipoxygenase protein appearing in the NF-kappaB immunoprecipitate was diminished .

In cells treated with agents that block <protein>5-lipoxygenase</protein> translocation to the nucleus , <protein>5-lipoxygenase</protein> protein appearing in the <protein>NF-kappaB</protein> immunoprecipitate was diminished .


Our results implicate an internal bipartite nuclear localizing sequence as a regulatory domain that modulates 5-lipoxygenase redistribution and catalysis in granulocytic cells .

Our results implicate an <protein>internal bipartite nuclear localizing sequence</protein> as a regulatory domain that modulates <protein>5-lipoxygenase</protein> redistribution and catalysis in <cell_type>granulocytic cells</cell_type> .


Additionally , our results suggest that molecular determinants which govern 5-lipoxygenase and NF-kappaB redistribution to the nucleus may be coordinately controlled in granulocytic cells .

Additionally , our results suggest that molecular determinants which govern 5-lipoxygenase and NF-kappaB redistribution to the nucleus may be coordinately controlled in <cell_type>granulocytic cells</cell_type> .


Copyright 1998 Academic Press .


Inhibition of CD28/CD3-mediated costimulation of naive and memory human T lymphocytes by intracellular incorporation of polyclonal antibodies specific for the activator protein-1 transcriptional complex .

Inhibition of CD28/CD3-mediated costimulation of <cell_type>naive and memory human T lymphocytes</cell_type> by intracellular incorporation of <protein>polyclonal antibodies</protein> specific for the <protein>activator protein-1 transcriptional complex</protein> .


A number of indirect methods have been utilized in demonstrating activator protein-1 transcription factor function in IL-2 promoter activity .

A number of indirect methods have been utilized in demonstrating <protein>activator protein-1</protein> transcription factor function in IL-2 promoter activity .


However , there has been no direct demonstration that activator protein-1 is involved in CD28-dependent costimulation of IL-2 gene transcription in freshly isolated naive and memory human T lymphocytes .

However , there has been no direct demonstration that <protein>activator protein-1</protein> is involved in CD28-dependent costimulation of <dna>IL-2 gene</dna> transcription in freshly isolated <cell_type>naive and memory human T lymphocytes</cell_type> .


To address this issue , the method of scrape loading was applied to purified peripheral blood T lymphocytes .

To address this issue , the method of scrape loading was applied to <cell_type>purified peripheral blood T lymphocytes</cell_type> .


Since scrape loading relies on adherent cells , peripheral blood human T ( PB-T ) cells were immobilized on the nonspecific cell attachment factor poly-L-lysine .

Since scrape loading relies on <cell_type>adherent cells</cell_type> , <cell_type>peripheral blood human T ( PB-T ) cells</cell_type> were immobilized on the nonspecific cell attachment factor poly-L-lysine .


Cells scraped off poly-L-lysine in the presence of Ig FITC efficiently incorporated Ig , with relatively uniform fluorescence .

Cells scraped off poly-L-lysine in the presence of <protein>Ig FITC</protein> efficiently incorporated Ig , with relatively uniform fluorescence .


T cells retained their physical parameters as measured by forward and side light scatter , and functional activity as measured by costimulation of proliferation and IL-2 production after being scraped off this substrate .

T cells retained their physical parameters as measured by forward and side light scatter , and functional activity as measured by costimulation of proliferation and <protein>IL-2</protein> production after being scraped off this substrate .


CD28/CD3-costimulated T cells produced intracellular IL-2 from all subsets measured ( CD4+ , CD4- , CD45RO+ , and CD45RO- ) .

<cell_type>CD28/CD3-costimulated T cells</cell_type> produced intracellular <protein>IL-2</protein> from all subsets measured ( <cell_type>CD4+</cell_type> , <cell_type>CD4-</cell_type> , <cell_type>CD45RO+</cell_type> , and <cell_type>CD45RO-</cell_type> ) .


IL-2 production and intracellular accumulation in nonscraped PB-T cells activated with CD28/CD3 coligation were skewed favoring CD45RO+ and CD4+ subsets , as was IL-2 production in scraped PB-T cells .

<protein>IL-2</protein> production and intracellular accumulation in nonscraped <cell_type>PB-T cells</cell_type> activated with CD28/CD3 coligation were skewed favoring <cell_type>CD45RO+ and CD4+ subsets</cell_type> , as was <protein>IL-2</protein> production in scraped <cell_type>PB-T cells</cell_type> .


The intracellular incorporation of Abs specific for c-Fos and c-Jun family members by scrape loading inhibited the production and intracellular accumulation of IL-2 within 6 h of costimulation with PMA/ionomycin , or costimulation by CD28 and CD3 ligation .

The intracellular incorporation of Abs specific for <protein>c-Fos and c-Jun family members</protein> by scrape loading inhibited the production and intracellular accumulation of <protein>IL-2</protein> within 6 h of costimulation with PMA/ionomycin , or costimulation by CD28 and CD3 ligation .


Scrape loading thus provides an efficient mechanism for intracellular incorporation of macromolecules , and the first direct evidence that c-Fos and c-Jun are involved in transcription of the IL-2 gene within its correct chromosomal context , in resting human T lymphocyte subpopulations .

Scrape loading thus provides an efficient mechanism for intracellular incorporation of macromolecules , and the first direct evidence that <protein>c-Fos</protein> and <protein>c-Jun</protein> are involved in transcription of the <dna>IL-2 gene</dna> within its correct chromosomal context , in resting human T lymphocyte subpopulations .


Differential expression of Nur77 family members in human T-lymphotropic virus type 1-infected cells : transactivation of the TR3/nur77 gene by Tax protein .

Differential expression of <protein>Nur77 family members</protein> in <cell_type>human T-lymphotropic virus type 1-infected cells</cell_type> : transactivation of the <dna>TR3/nur77 gene</dna> by <protein>Tax protein</protein> .


We analyzed the differential expression and regulation of three members of the Nur77 transcription factor family by the human T-lymphotropic virus type 1 ( HTLV-1 ) Tax protein .

We analyzed the differential expression and regulation of three members of the <protein>Nur77 transcription factor family</protein> by the human T-lymphotropic virus type 1 ( HTLV-1 ) <protein>Tax protein</protein> .


We have demonstrated that in both HTLV-1-infected cells and Tax-expressing JPX-9 cells , TR3/nur77 is highly expressed , whereas neither NOR-1 nor NOT expression is detectable .

We have demonstrated that in both <cell_type>HTLV-1-infected cells</cell_type> and <cell_line>Tax-expressing JPX-9 cells</cell_line> , <protein>TR3/nur77</protein> is highly expressed , whereas neither NOR-1 nor NOT expression is detectable .


Transient transfection analysis further confirmed the Tax transactivation of the TR3/nur77 promoter but not the NOR-1 promoter in different cell types .

Transient transfection analysis further confirmed the <protein>Tax</protein> transactivation of the <protein>TR3/nur77</protein> promoter but not the <dna>NOR-1 promoter</dna> in different cell types .


Furthermore , expression of a luciferase reporter gene driven by the NGFI-B ( rat homolog of TR3/Nur77 ) response element ( NBRE ) provided evidence that Tax -mediated transactivation resulted in the induction of a functional protein .

Furthermore , expression of a <dna>luciferase reporter gene</dna> driven by the <dna>NGFI-B ( rat homolog of TR3/Nur77 ) response element</dna> ( <dna>NBRE</dna> ) provided evidence that <protein>Tax</protein> -mediated transactivation resulted in the induction of a functional protein .


Cotransfection assays with the TR3/nur77 promoter sequence or the NBRE binding motif together with a series of Tax mutants have shown that Tax -induced TR3/nur77 expression is mediated by CREB/ATF-related transcription factors .

Cotransfection assays with the <dna>TR3/nur77 promoter sequence</dna> or the <dna>NBRE</dna> binding motif together with a series of <protein>Tax</protein> mutants have shown that <protein>Tax</protein> -induced <protein>TR3/nur77</protein> expression is mediated by <protein>CREB/ATF-related transcription factors</protein> .


Negative regulation of the heat shock transcriptional response by HSBP1 .

Negative regulation of the heat shock transcriptional response by <protein>HSBP1</protein> .


In response to stress , heat shock factor 1 ( HSF1 ) acquires rapid DNA binding and transient transcriptional activity while undergoing conformational transition from an inert non-DNA-binding monomer to active functional trimers .

In response to stress , <protein>heat shock factor 1</protein> ( <protein>HSF1</protein> ) acquires rapid DNA binding and transient transcriptional activity while undergoing conformational transition from an inert <protein>non-DNA-binding monomer</protein> to active functional trimers .


Attenuation of the inducible transcriptional response occurs during heat shock or upon recovery at non-stress conditions and involves dissociation of the HSF1 trimer and loss of activity .

Attenuation of the inducible transcriptional response occurs during heat shock or upon recovery at non-stress conditions and involves dissociation of the <protein>HSF1 trimer</protein> and loss of activity .


We have used the hydrophobic repeats of the HSF1 trimerization domain in the yeast two-hybrid protein interaction assay to identify heat shock factor binding protein 1 ( HSBP1 ) , a novel , conserved , 76-amino-acid protein that contains two extended arrays of hydrophobic repeats that interact with the HSF1 heptad repeats .

We have used the <protein>hydrophobic repeats</protein> of the <protein>HSF1</protein> trimerization domain in the yeast two-hybrid protein interaction assay to identify <protein>heat shock factor binding protein 1</protein> ( <protein>HSBP1</protein> ) , a novel , conserved , <protein>76-amino-acid protein</protein> that contains two extended arrays of <protein>hydrophobic repeats</protein> that interact with the <protein>HSF1 heptad repeats</protein> .


HSBP1 is nuclear-localized and interacts in vivo with the active trimeric state of HSF1 that appears during heat shock .

<protein>HSBP1</protein> is nuclear-localized and interacts in vivo with the active trimeric state of <protein>HSF1</protein> that appears during heat shock .


During attenuation of HSF1 to the inert monomer , HSBP1 associates with Hsp70 .

During attenuation of <protein>HSF1</protein> to the inert monomer , <protein>HSBP1</protein> associates with Hsp70 .


HSBP1 negatively affects HSF1 DNA-binding activity , and overexpression of HSBP1 in mammalian cells represses the transactivation activity of HSF1 .

<protein>HSBP1</protein> negatively affects <protein>HSF1</protein> DNA-binding activity , and overexpression of <protein>HSBP1</protein> in <cell_type>mammalian cells</cell_type> represses the transactivation activity of <protein>HSF1</protein> .


To establish a biological role for HSBP1 , the homologous Caenorhabditis elegans protein was overexpressed in body wall muscle cells and was shown to block activation of the heat shock response from a heat shock promoter-reporter construct .

To establish a biological role for <protein>HSBP1</protein> , the homologous <protein>Caenorhabditis elegans protein</protein> was overexpressed in <cell_type>body wall muscle cells</cell_type> and was shown to block activation of the heat shock response from a <dna>heat shock promoter-reporter construct</dna> .


Alteration in the level of HSBP1 expression in C. elegans has severe effects on survival of the animals after thermal and chemical stress , consistent with a role for HSBP1 as a negative regulator of the heat shock response .

Alteration in the level of <protein>HSBP1</protein> expression in C. elegans has severe effects on survival of the animals after thermal and chemical stress , consistent with a role for <protein>HSBP1</protein> as a negative regulator of the heat shock response .


Long-range transcriptional regulation of cytokine gene expression .


Most studies on the control of cytokine gene expression have involved the functional analysis of proximal promoters .

Most studies on the control of cytokine gene expression have involved the functional analysis of <dna>proximal promoters</dna> .


Recent work has identified distal elements that mediate long-range cytokine gene regulation and has implicated chromatin reorganization in regulation of cytokine gene loci .

Recent work has identified <dna>distal elements</dna> that mediate long-range cytokine gene regulation and has implicated chromatin reorganization in regulation of <dna>cytokine gene loci</dna> .


These studies have begun to elucidate the basis for cell-specificity and high-level expression of cytokine genes .

These studies have begun to elucidate the basis for cell-specificity and high-level expression of <dna>cytokine genes</dna> .


A signaling complex of Ca2+-calmodulin-dependent protein kinase IV and protein phosphatase 2A [ see comments ]

A signaling complex of <protein>Ca2+-calmodulin-dependent protein kinase IV</protein> and <protein>protein phosphatase 2A</protein> [ see comments ]


Stimulation of T lymphocytes results in a rapid increase in intracellular calcium concentration ( [ Ca2+ ] i ) that parallels the activation of Ca2+-calmodulin-dependent protein kinase IV ( CaMKIV ) , a nuclear enzyme that can phosphorylate and activate the cyclic adenosine monophosphate ( cAMP ) response element-binding protein ( CREB ) .

Stimulation of <cell_type>T lymphocytes</cell_type> results in a rapid increase in intracellular calcium concentration ( [ Ca2+ ] i ) that parallels the activation of <protein>Ca2+-calmodulin-dependent protein kinase IV</protein> ( <protein>CaMKIV</protein> ) , a <protein>nuclear enzyme</protein> that can phosphorylate and activate the <protein>cyclic adenosine monophosphate ( cAMP ) response element-binding protein</protein> ( <protein>CREB</protein> ) .


However , inactivation of CaMKIV occurs despite the sustained increase in [ Ca2+ ] i that is required for T cell activation .

However , inactivation of <protein>CaMKIV</protein> occurs despite the sustained increase in [ Ca2+ ] i that is required for T cell activation .


A stable and stoichiometric complex of CaMKIV with protein serine-threonine phosphatase 2A ( PP2A ) was identified in which PP2A dephosphorylates CaMKIV and functions as a negative regulator of CaMKIV signaling .

A stable and stoichiometric complex of <protein>CaMKIV</protein> with <protein>protein serine-threonine phosphatase 2A</protein> ( <protein>PP2A</protein> ) was identified in which <protein>PP2A</protein> dephosphorylates <protein>CaMKIV</protein> and functions as a negative regulator of <protein>CaMKIV</protein> signaling .


In Jurkat T cells , inhibition of PP2A activity by small t antigen enhanced activation of CREB -mediated transcription by CaMKIV .

In <cell_line>Jurkat T cells</cell_line> , inhibition of <protein>PP2A</protein> activity by small t antigen enhanced activation of <protein>CREB</protein> -mediated transcription by <protein>CaMKIV</protein> .


These findings reveal an intracellular signaling mechanism whereby a protein serine-threonine kinase ( CaMKIV ) is regulated by a tightly associated protein serine-threonine phosphatase ( PP2A ) .

These findings reveal an intracellular signaling mechanism whereby a <protein>protein serine-threonine kinase</protein> ( <protein>CaMKIV</protein> ) is regulated by a tightly associated <protein>protein serine-threonine phosphatase</protein> ( <protein>PP2A</protein> ) .


Hypoxia down-regulates MCP-1 expression : implications for macrophage distribution in tumors .

Hypoxia down-regulates <protein>MCP-1</protein> expression : implications for macrophage distribution in tumors .


Monocyte chemoattractant protein 1 ( MCP-1 ) is likely to contribute to the macrophage infiltrate in human ovarian carcinomas .

<protein>Monocyte chemoattractant protein 1</protein> ( <protein>MCP-1</protein> ) is likely to contribute to the <cell_type>macrophage infiltrate</cell_type> in human ovarian carcinomas .


Although MCP-1 is predominantly expressed by the tumor parenchyma , macrophages accumulate at highest density in necrotic regions , which are associated with low oxygen tensions .

Although <protein>MCP-1</protein> is predominantly expressed by the tumor parenchyma , macrophages accumulate at highest density in necrotic regions , which are associated with low oxygen tensions .


Tumor necrosis factor alpha ( TNF-alpha ) can stimulate MCP-1 production and is also present within ovarian carcinomas .

<protein>Tumor necrosis factor alpha</protein> ( <protein>TNF-alpha</protein> ) can stimulate <protein>MCP-1</protein> production and is also present within ovarian carcinomas .


We have investigated the effect of hypoxia both on MCP-1 expression in ovarian cancer cell lines and monocyte migration .

We have investigated the effect of hypoxia both on <protein>MCP-1</protein> expression in <cell_line>ovarian cancer cell lines</cell_line> and monocyte migration .


Hypoxia down-regulated TNF-alpha-induced MCP-1 mRNA and protein production by ovarian cancer cells .

Hypoxia down-regulated <rna>TNF-alpha-induced MCP-1 mRNA</rna> and protein production by <cell_type>ovarian cancer cells</cell_type> .


The effect was mimicked by cobalt chloride and desferrioxamine , consistent with a specific oxygen-sensing mechanism .


Unlike antioxidants , hypoxia did not inhibit nuclear factor KB mobilization .


Monocyte migration in response to MCP-1 was also diminished under hypoxic conditions .

Monocyte migration in response to <protein>MCP-1</protein> was also diminished under hypoxic conditions .


Down-regulation of MCP-1 expression and the inhibition of monocyte migration are independent effects of hypoxia that may contribute to the distribution of macrophages within ovarian tumors .

Down-regulation of <protein>MCP-1</protein> expression and the inhibition of monocyte migration are independent effects of hypoxia that may contribute to the distribution of <cell_type>macrophages</cell_type> within ovarian tumors .


Activation of nuclear factor kappa B inflammatory bowel disease [ see comments ]

Activation of <protein>nuclear factor kappa B</protein> inflammatory bowel disease [ see comments ]


BACKGROUND : Expression of pro-inflammatory cytokines is increased in the intestinal lamina propria of patients with inflammatory bowel disease ( IBD ) .

BACKGROUND : Expression of <protein>pro-inflammatory cytokines</protein> is increased in the intestinal lamina propria of patients with inflammatory bowel disease ( IBD ) .


Nuclear factor kappa B ( NF kappa B ) controls transcription of inflammation genes .

<protein>Nuclear factor kappa B</protein> ( <protein>NF kappa B</protein> ) controls transcription of <dna>inflammation genes</dna> .


On activation , NF kappa B is rapidly released from its cytoplasmic inhibitor ( I kappa B ) , transmigrates into the nucleus , and binds to DNA response elements in gene promoter regions .

On activation , <protein>NF kappa B</protein> is rapidly released from its <protein>cytoplasmic inhibitor</protein> ( <protein>I kappa B</protein> ) , transmigrates into the nucleus , and binds to <dna>DNA response elements</dna> in gene promoter regions .


AIMS : To investigate whether increased activation of NF kappa B is important in IBD and may be down-regulated by anti-inflammatory treatment .

AIMS : To investigate whether increased activation of <protein>NF kappa B</protein> is important in IBD and may be down-regulated by anti-inflammatory treatment .


METHODS : Activation of NF kappa B was determined by western blot assessment and electrophoretic mobility shift assay in nuclear extracts of colonic biopsy samples as well as lamina propria mononuclear cells .

METHODS : Activation of <protein>NF kappa B</protein> was determined by western blot assessment and electrophoretic mobility shift assay in nuclear extracts of colonic biopsy samples as well as <cell_type>lamina propria mononuclear cells</cell_type> .


RESULTS : Nuclear levels of NF kappa B p65 are increased in lamina propria biopsy specimens from patients with Crohn 's disease in comparison with patients with ulcerative colitis and controls .

RESULTS : Nuclear levels of <protein>NF kappa B</protein> <protein>p65</protein> are increased in lamina propria biopsy specimens from patients with Crohn 's disease in comparison with patients with ulcerative colitis and controls .


Increased activation of NF kappa B was detected in lamina propria mononuclear cells from patients with active IBD .

Increased activation of <protein>NF kappa B</protein> was detected in <cell_type>lamina propria mononuclear cells</cell_type> from patients with active IBD .


Corticosteroids strongly inhibit intestinal NF kappa B activation in IBD in vivo and in vitro by stabilising the cytosolic inhibitor I kappa B alpha against activation induced degradation .

Corticosteroids strongly inhibit intestinal <protein>NF kappa B</protein> activation in IBD in vivo and in vitro by stabilising the <protein>cytosolic inhibitor</protein> <protein>I kappa B</protein> alpha against activation induced degradation .


CONCLUSIONS : In both IBDs , but particularly Crohn 's disease , increased activation of NF kappa B may be involved in the regulation of the inflammatory response .

CONCLUSIONS : In both IBDs , but particularly Crohn 's disease , increased activation of <protein>NF kappa B</protein> may be involved in the regulation of the inflammatory response .


Inhibition of NF kappa B activation may represent a mechanism by which steroids exert an anti-inflammatory effect in IBD

Inhibition of <protein>NF kappa B</protein> activation may represent a mechanism by which steroids exert an anti-inflammatory effect in IBD


Insufficient glycemic control increases nuclear factor-kappa B binding activity in peripheral blood mononuclear cells isolated from patients with type 1 diabetes .

Insufficient glycemic control increases <protein>nuclear factor-kappa B</protein> binding activity in <cell_type>peripheral blood mononuclear cells</cell_type> isolated from patients with type 1 diabetes .


OBJECTIVE : The redox-sensitive transcription factor nuclear factor-kappa B ( NF-kappa B ) is believed to contribute to late diabetic complications .

OBJECTIVE : The <protein>redox-sensitive transcription factor nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) is believed to contribute to late diabetic complications .


It is unknown whether NF-kappa B is influenced by glycemic control .

It is unknown whether <protein>NF-kappa B</protein> is influenced by glycemic control .


RESEARCH DESIGN AND METHODS : To determine whether NF-kappa B is activated in patients with insufficient glycemic control ( HbA1c > 10 % ) , we developed a tissue culture-independent electrophoretic mobility shift assay ( EMSA ) -based semiquantitative detection system that allowed us to determine NF-kappa B activation in ex vivo-isolated peripheral blood mononuclear cells ( PBMCs ) .

RESEARCH DESIGN AND METHODS : To determine whether <protein>NF-kappa B</protein> is activated in patients with insufficient glycemic control ( HbA1c > 10 % ) , we developed a tissue culture-independent electrophoretic mobility shift assay ( EMSA ) -based semiquantitative detection system that allowed us to determine <protein>NF-kappa B</protein> activation in ex vivo-isolated <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMCs</cell_type> ) .


We included 43 patients with type 1 diabetes in this cross-sectional study .


10 of those received the antioxidant thioctic acid ( 600 mg/day p.o. ) for 2 weeks .


RESULTS : Monocytes of patients with HbA1c levels > 10 % demonstrated significantly higher NF-kappa B binding activity in an EMSA and a stronger NF-kappa B staining in immunohistochemistry than monocytes of patients with HbA1c levels of 6-8 % .

RESULTS : Monocytes of patients with HbA1c levels > 10 % demonstrated significantly higher <protein>NF-kappa B</protein> binding activity in an EMSA and a stronger <protein>NF-kappa B</protein> staining in immunohistochemistry than <cell_type>monocytes</cell_type> of patients with HbA1c levels of 6-8 % .


The increase in NF-kappa B activation correlated with an increase in plasmatic markers of lipid peroxidation .

The increase in <protein>NF-kappa B</protein> activation correlated with an increase in plasmatic markers of lipid peroxidation .


Treatment with the antioxidant thioctic acid decreased NF-kappa B binding activity .

Treatment with the antioxidant thioctic acid decreased <protein>NF-kappa B</protein> binding activity .


CONCLUSIONS : Hyperglycemia induces activation of the transcription factor NF-kappa B in ex vivo-isolated PBMCs of patients with type 1 diabetes .

CONCLUSIONS : Hyperglycemia induces activation of the transcription factor <protein>NF-kappa B</protein> in ex vivo-isolated <cell_type>PBMCs</cell_type> of patients with type 1 diabetes .


NF-kappa B activation is at least partially dependent on oxidative stress , since the antioxidant thioctic acid significantly lowered the extent of NF-kappa B binding activity .

<protein>NF-kappa B</protein> activation is at least partially dependent on oxidative stress , since the antioxidant thioctic acid significantly lowered the extent of <protein>NF-kappa B</protein> binding activity .


Synergistic activation of MAP kinase ( ERK1/2 ) by erythropoietin and stem cell factor is essential for expanded erythropoiesis .

Synergistic activation of <protein>MAP kinase</protein> ( <protein>ERK1/2</protein> ) by <protein>erythropoietin</protein> and <protein>stem cell factor</protein> is essential for expanded erythropoiesis .


Stem cell factor ( SCF ) and erythropoietin ( EPO ) work synergistically to support erythropoiesis , but the mechanism for this synergism is unknown .

<protein>Stem cell factor</protein> ( <protein>SCF</protein> ) and <protein>erythropoietin</protein> ( <protein>EPO</protein> ) work synergistically to support erythropoiesis , but the mechanism for this synergism is unknown .


By using purified human erythroid colony-forming cells ( ECFC ) , we have found that SCF and EPO synergistically activate MAP kinase ( MAPK , ERK1/2 ) , which correlates with the cell growth and thus may be responsible for the synergistic effects .

By using <cell_line>purified human erythroid colony-forming cells</cell_line> ( <cell_line>ECFC</cell_line> ) , we have found that <protein>SCF</protein> and <protein>EPO</protein> synergistically activate <protein>MAP kinase</protein> ( <protein>MAPK</protein> , <protein>ERK1/2</protein> ) , which correlates with the cell growth and thus may be responsible for the synergistic effects .


Treatment of the cells with PD98059 and wortmannin , inhibitors of MEK and PI-3 kinase , respectively , inhibited the synergistic activation of MAPK and also the cell growth , further supporting this conclusion .

Treatment of the cells with PD98059 and wortmannin , inhibitors of <protein>MEK</protein> and <protein>PI-3 kinase</protein> , respectively , inhibited the synergistic activation of <protein>MAPK</protein> and also the cell growth , further supporting this conclusion .


Wortmannin only inhibits MAPK activation induced by EPO but not that by SCF , suggesting that SCF and EPO may activate MAPK through different pathways , which would facilitate synergy .

Wortmannin only inhibits <protein>MAPK</protein> activation induced by <protein>EPO</protein> but not that by <protein>SCF</protein> , suggesting that <protein>SCF</protein> and <protein>EPO</protein> may activate <protein>MAPK</protein> through different pathways , which would facilitate synergy .


Furthermore , EPO , but not SCF , led to activation of STAT5 , whereas SCF and wortmannin had no effect on the EPO -induced STAT5 activation , suggesting that STAT5 is not involved in the synergistic action of SCF and EPO .

Furthermore , <protein>EPO</protein> , but not <protein>SCF</protein> , led to activation of <protein>STAT5</protein> , whereas <protein>SCF</protein> and wortmannin had no effect on the <protein>EPO</protein> -induced <protein>STAT5</protein> activation , suggesting that <protein>STAT5</protein> is not involved in the synergistic action of <protein>SCF</protein> and <protein>EPO</protein> .


Together , the data suggest that synergistic activation of MAPK by SCF and EPO is essential for expanded erythropoiesis .

Together , the data suggest that synergistic activation of <protein>MAPK</protein> by <protein>SCF</protein> and <protein>EPO</protein> is essential for expanded erythropoiesis .


Copyright 1998 by The American Society of Hematology .


The molecular and phenotypic profile of primary central nervous system lymphoma identifies distinct categories of the disease and is consistent with histogenetic derivation from germinal center-related B cells .

The molecular and phenotypic profile of primary central nervous system lymphoma identifies distinct categories of the disease and is consistent with histogenetic derivation from <cell_type>germinal center-related B cells</cell_type> .


Primary central nervous system lymphoma ( PCNSL ) is a major cause of morbidity and mortality among human immunodeficiency virus ( HIV ) -infected individuals .


The precise histogenetic derivation and the molecular pathogenesis of PCNSL is poorly understood .


In an attempt to clarify the histogenesis and pathogenesis of these lymphomas , 49 PCNSL ( 26 acquired immunodeficiency syndrome [ AIDS ] -related and 23 AIDS-unrelated ) were analyzed for multiple biologic markers , which are known to bear histogenetic and pathogenetic significance for mature B-cell neoplasms .


PCNSL associated frequently ( 50.0 % ) with mutations of BCL-6 5 ' noncoding regions , which are regarded as a marker of B-cell transition through the germinal center ( GC ) .

PCNSL associated frequently ( 50.0 % ) with mutations of <dna>BCL-6 5 ' noncoding regions</dna> , which are regarded as a marker of B-cell transition through the germinal center ( GC ) .


Expression of BCL-6 protein , which is restricted to GC B cells throughout physiologic B-cell maturation , was detected in 100 % AIDS-unrelated PCNSL and in 56.2 % AIDS-related cases .

Expression of <protein>BCL-6 protein</protein> , which is restricted to <cell_type>GC B cells</cell_type> throughout physiologic B-cell maturation , was detected in 100 % AIDS-unrelated PCNSL and in 56.2 % AIDS-related cases .


Notably , among AIDS-related PCNSL , expression of BCL-6 was mutually exclusive with expression of Epstein-Barr virus ( EBV ) -encoded latent membrane protein ( LMP ) -1 and , with few exceptions , also of BCL-2 .

Notably , among AIDS-related PCNSL , expression of <protein>BCL-6</protein> was mutually exclusive with expression of <protein>Epstein-Barr virus ( EBV ) -encoded latent membrane protein ( LMP ) -1</protein> and , with few exceptions , also of <protein>BCL-2</protein> .


All but one PCNSL expressed hMSH2 , which among mature B cells selectively stains GC B cells .

All but one PCNSL expressed hMSH2 , which among <cell_type>mature B cells</cell_type> selectively stains <cell_type>GC B cells</cell_type> .


These data suggest that PCNSL may be frequently related to GC B cells and may be segregated into two major biologic categories based on the expression pattern of BCL-6 , LMP-1 , and BCL-2 .

These data suggest that PCNSL may be frequently related to <cell_type>GC B cells</cell_type> and may be segregated into two major biologic categories based on the expression pattern of <protein>BCL-6</protein> , <protein>LMP-1</protein> , and <protein>BCL-2</protein> .


BCL-6 ( + ) / LMP-1 ( - ) / BCL-2 ( - ) PCNSL occur both in the presence and in the absence of HIV infection and consistently display a large noncleaved cell morphology .

<protein>BCL-6</protein> ( + ) / <protein>LMP-1</protein> ( - ) / <protein>BCL-2</protein> ( - ) PCNSL occur both in the presence and in the absence of HIV infection and consistently display a large noncleaved cell morphology .


Conversely , BCL-6 ( - ) / LMP-1 ( + ) / BCL-2 ( + ) PCNSL are restricted to HIV-infected hosts and are represented by lymphomas with immunoblastic features .

Conversely , <protein>BCL-6</protein> ( - ) / <protein>LMP-1</protein> ( + ) / <protein>BCL-2</protein> ( + ) PCNSL are restricted to HIV-infected hosts and are represented by lymphomas with immunoblastic features .


These data are relevant for the pathogenesis and histogenesis of PCNSL and may be helpful to segregate distinct biologic and prognostic categories of these lymphomas .


Antioxidant regulation of phorbol ester-induced adhesion of human Jurkat T-cells to endothelial cells .

Antioxidant regulation of phorbol ester-induced adhesion of <cell_line>human Jurkat T-cells</cell_line> to <cell_type>endothelial cells</cell_type> .


Regulation of adhesion molecule expression and function by reactive oxygen species via specific redox sensitive mechanisms have been reported .


The effects of clinically safe antioxidants in the regulation of adhesion molecule expression in human endothelial cells ( ECV ) , and adherence of human Jurkat T cells to ECV cells were investigated .

The effects of clinically safe antioxidants in the regulation of adhesion molecule expression in <cell_type>human endothelial cells</cell_type> ( ECV ) , and adherence of <cell_line>human Jurkat T cells</cell_line> to <cell_type>ECV cells</cell_type> were investigated .


The thiol antioxidant , alpha-lipoate , at clinically relevant doses down-regulated phorbol 12-myristate 13-acetate ( PMA ) -induced adhesion molecule expression and cell-cell adhesion .


Inhibition of PMA-induced ICAM-1 and VCAM-1 expression as well as PMA-induced adhesion of Jurkat T-cells to ECV cells by alpha-lipoate was dose dependent ( 50-250 microM ) .

Inhibition of PMA-induced ICAM-1 and VCAM-1 expression as well as PMA-induced adhesion of <cell_line>Jurkat T-cells</cell_line> to <cell_type>ECV cells</cell_type> by alpha-lipoate was dose dependent ( 50-250 microM ) .


The effect was significant for ICAM-1 ( p < .01 ) and VCAM-1 ( p < .01 ) expression in cells pretreated with 100 microM alpha-lipoate compared to PMA-activated untreated cells .

The effect was significant for <protein>ICAM-1</protein> ( p < .01 ) and <protein>VCAM-1</protein> ( p < .01 ) expression in cells pretreated with 100 microM alpha-lipoate compared to <cell_type>PMA-activated untreated cells</cell_type> .


Inhibition of PMA-induced adhesion molecule expression and cell-cell adhesion was more pronounced when a combination of antioxidants , alpha-lipoate and alpha-tocopherol , were used compared to the use of either of these antioxidant alone .


The regulation of adhesion molecule expression and function by low concentration of antioxidants investigated does not appear to be NF-kappaB regulated or transcription dependent because no change in the mRNA response was observed .

The regulation of adhesion molecule expression and function by low concentration of antioxidants investigated does not appear to be <protein>NF-kappaB</protein> regulated or transcription dependent because no change in the mRNA response was observed .


Protein kinase C ( PKC ) has been suggested to regulate PMA-induced adhesion molecule expression by post-transcriptional stabilization of adhesion molecule mRNA .

<protein>Protein kinase C</protein> ( <protein>PKC</protein> ) has been suggested to regulate PMA-induced adhesion molecule expression by post-transcriptional stabilization of <rna>adhesion molecule mRNA</rna> .


Alpha-lipoate pretreatment did not influence the response of PKC activity to PMA .

Alpha-lipoate pretreatment did not influence the response of <protein>PKC</protein> activity to PMA .


Oxidants are known to be involved in the regulation of cell adhesion processes .


Treatment of ECV cells with PMA induced generation of intracellular oxidants .

Treatment of <cell_type>ECV cells</cell_type> with PMA induced generation of intracellular oxidants .


Alpha-lipoate ( 100 or 250 microM ) treatment decreased PMA-induced generation of intracellular oxidants .


The inhibitory effect of low concentration of alpha-lipaote alone or in combination with alpha-tocopherol on agonist-induced adhesion processes observed in this study may be of potential therapeutic value .


Binding of human immunodeficiency virus type 1 to CD4 and CXCR4 receptors differentially regulates expression of inflammatory genes and activates the MEK /ERK signaling pathway .

Binding of human immunodeficiency virus type 1 to <protein>CD4 and CXCR4 receptors</protein> differentially regulates expression of <dna>inflammatory genes</dna> and activates the <protein>MEK</protein> /ERK signaling pathway .


We have previously shown that binding of human immunodeficiency virus type 1 ( HIV-1 ) virions to CD4 receptors stimulates association of Lck with Raf-1 and results in the activation of Raf-1 kinase in a Ras-independent manner .

We have previously shown that binding of human immunodeficiency virus type 1 ( HIV-1 ) virions to <protein>CD4 receptors</protein> stimulates association of <protein>Lck</protein> with <protein>Raf-1</protein> and results in the activation of <protein>Raf-1</protein> kinase in a Ras-independent manner .


In the present study , we demonstrate that HIV-1 envelope glycoproteins of both T-cell-tropic and macrophagetropic strains rapidly activate the ERK/mitogen-activated protein ( MAP ) kinase pathway and the binding of nuclear transcription factors ( AP-1 , NF-kappaB , and C/EBP ) and stimulate expression of cytokine and chemokine genes .

In the present study , we demonstrate that <protein>HIV-1 envelope glycoproteins</protein> of both T-cell-tropic and macrophagetropic strains rapidly activate the ERK/mitogen-activated protein ( MAP ) kinase pathway and the binding of <protein>nuclear transcription factors</protein> ( <protein>AP-1</protein> , <protein>NF-kappaB</protein> , and <protein>C/EBP</protein> ) and stimulate expression of <dna>cytokine and chemokine genes</dna> .


The activation of this signaling pathway requires functional CD4 receptors and is independent of binding to CXCR4 .

The activation of this signaling pathway requires functional <protein>CD4 receptors</protein> and is independent of binding to <protein>CXCR4</protein> .


Binding of the natural ligand stromal cell-derived factor 1 ( SDF-1 ) to CXCR4 , which inhibits entry of T-cell-tropic HIV-1 , activates also the ERK/ MAP kinase pathway .

Binding of the natural ligand <protein>stromal cell-derived factor 1</protein> ( <protein>SDF-1</protein> ) to <protein>CXCR4</protein> , which inhibits entry of T-cell-tropic HIV-1 , activates also the ERK/ <protein>MAP kinase</protein> pathway .


However , SDF-1 did not affect the CD4-mediated expression of cytokine and chemokine genes .

However , <protein>SDF-1</protein> did not affect the CD4-mediated expression of <dna>cytokine and chemokine genes</dna> .


These results provide firm molecular evidence that binding of HIV-1 envelope glycoproteins to CD4 receptor initiates a signaling pathway ( s ) independent of the binding to the chemokine receptor that leads to the aberrant expression of inflammatory genes and may contribute significantly to HIV-1 replication as well as to deregulation of the immune system .

These results provide firm molecular evidence that binding of <protein>HIV-1 envelope glycoproteins</protein> to <protein>CD4 receptor</protein> initiates a signaling pathway ( s ) independent of the binding to the <protein>chemokine receptor</protein> that leads to the aberrant expression of <dna>inflammatory genes</dna> and may contribute significantly to HIV-1 replication as well as to deregulation of the immune system .


Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor .

Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the <protein>BCL-6</protein> <protein>transcription factor</protein> .


The bcl-6 proto-oncogene encodes a POZ/zinc finger transcriptional repressor expressed in germinal center ( GC ) B and T cells and required for GC formation and antibody affinity maturation .

The <dna>bcl-6 proto-oncogene</dna> encodes a <protein>POZ/zinc finger transcriptional repressor</protein> expressed in <cell_type>germinal center ( GC ) B and T cells</cell_type> and required for GC formation and antibody affinity maturation .


Deregulation of bcl-6 expression by chromosomal rearrangements and point mutations of the bcl-6 promoter region are implicated in the pathogenesis of B-cell lymphoma .

Deregulation of <dna>bcl-6</dna> expression by chromosomal rearrangements and point mutations of the <dna>bcl-6 promoter region</dna> are implicated in the pathogenesis of B-cell lymphoma .


The signals regulating bcl-6 expression are not known .

The signals regulating <dna>bcl-6</dna> expression are not known .


Here we show that antigen receptor activation leads to BCL-6 phosphorylation by mitogen-activated protein kinase ( MAPK ) .

Here we show that antigen receptor activation leads to <protein>BCL-6</protein> phosphorylation by <protein>mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) .


Phosphorylation , in turn , targets BCL-6 for rapid degradation by the ubiquitin / proteasome pathway .

Phosphorylation , in turn , targets <protein>BCL-6</protein> for rapid degradation by the <protein>ubiquitin</protein> / <protein>proteasome</protein> pathway .


These findings indicate that BCL-6 expression is directly controlled by the antigen receptor via MAPK activation .

These findings indicate that <protein>BCL-6</protein> expression is directly controlled by the antigen receptor via <protein>MAPK</protein> activation .


This signaling pathway may be crucial for the control of B-cell differentiation and antibody response and has implications for the regulation of other POZ/zinc finger transcription factors in other tissues .

This signaling pathway may be crucial for the control of B-cell differentiation and antibody response and has implications for the regulation of other <protein>POZ/zinc finger transcription factors</protein> in other tissues .


Glucocorticoid receptors are differentially expressed in the cells and tissues of the immune system .

<protein>Glucocorticoid receptors</protein> are differentially expressed in the cells and tissues of the immune system .


Cytosolic glucocorticoid receptor ( GR ) binding studies on immune tissues demonstrate that the thymus exhibits three to four times higher levels of GR protein than the spleen .

<protein>Cytosolic glucocorticoid receptor</protein> ( <protein>GR</protein> ) binding studies on immune tissues demonstrate that the thymus exhibits three to four times higher levels of <protein>GR protein</protein> than the spleen .


High levels of GR are consistent with the exquisite sensitivity of the thymus to glucocorticoid exposure .

High levels of <protein>GR</protein> are consistent with the exquisite sensitivity of the thymus to glucocorticoid exposure .


Nevertheless , whole cell binding studies reveal similar levels of GR in immature thymic T lymphocytes and more mature , splenic T lymphocytes .

Nevertheless , whole cell binding studies reveal similar levels of <protein>GR</protein> in <cell_type>immature thymic T lymphocytes</cell_type> and more mature , <cell_type>splenic T lymphocytes</cell_type> .


Moreover , whole cell binding techniques indicate that neutrophils ( which represent roughly 30 % of splenic leukocytes ) exhibit higher GR than both T and B lymphocytes , further contradicting results from cytosolic binding studies .

Moreover , whole cell binding techniques indicate that <cell_type>neutrophils</cell_type> ( which represent roughly 30 % of <cell_type>splenic leukocytes</cell_type> ) exhibit higher <protein>GR</protein> than both <cell_type>T and B lymphocytes</cell_type> , further contradicting results from cytosolic binding studies .


To address these inconsistencies , GR protein was assessed in immune cells and tissues using cytosolic radioligand binding .

To address these inconsistencies , <protein>GR protein</protein> was assessed in <cell_type>immune cells and tissues</cell_type> using cytosolic radioligand binding .


Western blot analysis , and immunocytochemistry .


Consistent with previous cytosolic receptor binding studies on immune tissue homogenates , thymic T cells were found to have higher levels of GR than T cells isolated from the spleen .

Consistent with previous cytosolic receptor binding studies on immune tissue homogenates , thymic <cell_type>T cells</cell_type> were found to have higher levels of <protein>GR</protein> than <cell_type>T cells</cell_type> isolated from the spleen .


In addition , neutrophils were found to have fewer GR than lymphocytes and monocytes .

In addition , neutrophils were found to have fewer <protein>GR</protein> than <cell_type>lymphocytes</cell_type> and <cell_type>monocytes</cell_type> .


These results indicate a meaningful relationship between receptor expression and known sensitivity to glucocorticoids .


Functional replacement of the mouse E2A gene with a human HEB cDNA .

Functional replacement of the <dna>mouse E2A gene</dna> with a <dna>human HEB cDNA</dna> .


The mammalian E2A , HEB , and E2-2 genes encode a unique class of basic helix-loop-helix ( bHLH ) transcription factors that are evolutionarily conserved and essential for embryonic and postnatal development .

The <dna>mammalian E2A , HEB , and E2-2 genes</dna> encode a unique class of <protein>basic helix-loop-helix ( bHLH ) transcription factors</protein> that are evolutionarily conserved and essential for embryonic and postnatal development .


While the structural and functional similarities among the gene products are well demonstrated , it is not clear why deletion of E2A , but not HEB or E2-2 , leads to a complete arrest in B-lymphocyte development .

While the structural and functional similarities among the <protein>gene products</protein> are well demonstrated , it is not clear why deletion of <dna>E2A</dna> , but not <dna>HEB</dna> or <dna>E2-2</dna> , leads to a complete arrest in B-lymphocyte development .


To understand the molecular basis of the functional specificity between E2A and HEB / E2-2 in mammalian development , we generated and tested a panel of E2A knockin mutations including subtle mutations in the E12 and E47 exons and substitution of both E12 and E47 exons with a human HEB cDNA .

To understand the molecular basis of the functional specificity between <dna>E2A</dna> and <dna>HEB</dna> / <dna>E2-2</dna> in mammalian development , we generated and tested a panel of <dna>E2A</dna> knockin mutations including subtle mutations in the <dna>E12 and E47 exons</dna> and substitution of both <dna>E12 and E47 exons</dna> with a <dna>human HEB cDNA</dna> .


We find that the alternatively spliced E12 and E47 bHLH proteins of the E2A gene play similar and additive roles in supporting B lymphopoiesis .

We find that the alternatively spliced <protein>E12 and E47 bHLH proteins</protein> of the <dna>E2A gene</dna> play similar and additive roles in supporting <cell_type>B lymphopoiesis</cell_type> .


Further , we find that HEB driven by the endogenous E2A promoter can functionally replace E2A in supporting B-cell commitment and differentiation toward completion .

Further , we find that <dna>HEB</dna> driven by the <dna>endogenous E2A promoter</dna> can functionally replace <dna>E2A</dna> in supporting B-cell commitment and differentiation toward completion .


Finally , the postnatal lethality associated with E2A disruption is fully rescued by the addition of HEB .

Finally , the postnatal lethality associated with <dna>E2A</dna> disruption is fully rescued by the addition of <dna>HEB</dna> .


This study suggests that the functional divergence among E12 , E47 , and HEB in different cell types is partially defined by the context of gene expression .

This study suggests that the functional divergence among <dna>E12</dna> , <dna>E47</dna> , and <dna>HEB</dna> in different cell types is partially defined by the context of gene expression .


Biased dependency of CD80 versus CD86 in the induction of transcription factors regulating the human IL-2 promoter .

Biased dependency of <protein>CD80</protein> versus <protein>CD86</protein> in the induction of <protein>transcription factors</protein> regulating the <dna>human IL-2 promoter</dna> .


In addition to the signals obtained by ligation of the TCR , T cells need additional , co-stimulatory signals to be activated .

In addition to the signals obtained by ligation of the TCR , <cell_type>T cells</cell_type> need additional , co-stimulatory signals to be activated .


One such co-stimulatory signal is delivered when CD28 on T cells binds to CD80 or CD86 on antigen-presenting cells ( APC ) .

One such co-stimulatory signal is delivered when <protein>CD28</protein> on <cell_type>T cells</cell_type> binds to <protein>CD80</protein> or <protein>CD86</protein> on <cell_type>antigen-presenting cells</cell_type> ( <cell_type>APC</cell_type> ) .


In the present study , we analyzed the ability of CD80 and CD86 to co-stimulate human T cells activated by superantigen .

In the present study , we analyzed the ability of <protein>CD80</protein> and <protein>CD86</protein> to <cell_type>co-stimulate human T cells</cell_type> activated by superantigen .


Using the Raji B cell lymphoma , which express similar levels of CD80 and CD86 , it was found that T cell proliferation was mainly co-stimulated by CD80 .

Using the <cell_line>Raji B cell lymphoma</cell_line> , which express similar levels of <protein>CD80</protein> and <protein>CD86</protein> , it was found that T cell proliferation was mainly co-stimulated by <protein>CD80</protein> .


To further characterize the consequences of this biased co-stimulatory dependency , we employed a well-defined system of transfected CHO cells expressing human MHC class II together with CD80 , CD86 or CD80 and CD86 .

To further characterize the consequences of this biased co-stimulatory dependency , we employed a well-defined system of transfected <cell_line>CHO cells</cell_line> expressing <protein>human MHC class II</protein> together with <protein>CD80</protein> , <protein>CD86</protein> or <protein>CD80</protein> and <protein>CD86</protein> .


Proliferation of freshly prepared CD4+ T cells required the presence of either CD80 or CD86 .

Proliferation of freshly prepared <cell_type>CD4+ T cells</cell_type> required the presence of either <protein>CD80</protein> or <protein>CD86</protein> .


However , IL-2 production reached only suboptimal levels in the presence of CD86 but optimal levels with CD80 .

However , <protein>IL-2</protein> production reached only suboptimal levels in the presence of <protein>CD86</protein> but optimal levels with <protein>CD80</protein> .


To analyze IL-2 transcriptional activity in CD80 and CD86 co-stimulated T cells we used Jurkat T cells transfected with luciferase reporter gene constructs .

To analyze <protein>IL-2</protein> transcriptional activity in <protein>CD80</protein> and <protein>CD86</protein> co-stimulated <cell_type>T cells</cell_type> we used <cell_line>Jurkat T cells</cell_line> transfected with <dna>luciferase reporter gene constructs</dna> .


CD80 induced higher levels of IL-2 promoter -enhancer activity compared to CD86 .

<protein>CD80</protein> induced higher levels of <dna>IL-2 promoter</dna> -enhancer activity compared to <protein>CD86</protein> .


Furthermore , the activity of transcription factors regulating the IL-2 promoter-enhancer region including activation protein-1 , CD28 response element and nuclear factor kappaB were 4-8 times higher after CD80 compared to CD86 ligation .

Furthermore , the activity of <protein>transcription factors</protein> regulating the <dna>IL-2 promoter-enhancer region</dna> including <protein>activation protein-1</protein> , <dna>CD28 response element</dna> and <protein>nuclear factor kappaB</protein> were 4-8 times higher after <protein>CD80</protein> compared to <protein>CD86</protein> ligation .


Our results suggest that the eventual appearance of CD80 on recently activated CD86+ APC is important for the superinduction of IL-2 production and to support vigorous T cell proliferation .

Our results suggest that the eventual appearance of <protein>CD80</protein> on recently activated <cell_type>CD86+ APC</cell_type> is important for the superinduction of <protein>IL-2</protein> production and to support vigorous T cell proliferation .


Duplication of the DR3 gene on human chromosome 1p36 and its deletion in human neuroblastoma .

Duplication of the <dna>DR3 gene</dna> on <dna>human chromosome 1p36</dna> and its deletion in <cell_type>human neuroblastoma</cell_type> .


The human DR3 gene , whose product is also known as Wsl-1/APO-3/TRAMP/LARD , encodes a tumor necrosis factor-related receptor that is expressed primarily on the surface of thymocytes and lymphocytes .

The <dna>human DR3 gene</dna> , whose product is also known as <protein>Wsl-1/APO-3/TRAMP/LARD</protein> , encodes a <protein>tumor necrosis factor-related receptor</protein> that is expressed primarily on the surface of <cell_type>thymocytes</cell_type> and <cell_type>lymphocytes</cell_type> .


DR3 is capable of inducing both NF-kappa B activation and apoptosis when overexpressed in mammalian cells , although its ligand has not yet been identified .

<protein>DR3</protein> is capable of inducing both <protein>NF-kappa B</protein> activation and apoptosis when overexpressed in <cell_type>mammalian cells</cell_type> , although its ligand has not yet been identified .


We report here that the DR3 gene locus is tandemly duplicated on human chromosome band 1p36.2-p36.3 and that these genes are hemizygously deleted and/or translocated to another chromosome in neuroblastoma ( NB ) cell lines with amplified MYCN .

We report here that the <dna>DR3 gene locus</dna> is tandemly duplicated on <dna>human chromosome band 1p36.2-p36.3</dna> and that these genes are hemizygously deleted and/or translocated to another chromosome in <cell_line>neuroblastoma ( NB ) cell lines</cell_line> with amplified MYCN .


Duplication of at least a portion of the DR3 gene , including the extracellular and transmembrane regions but not the cytoplasmic domain , was demonstrated by both fluorescence in situ hybridization and genomic Southern blotting .

Duplication of at least a portion of the <dna>DR3 gene</dna> , including the <protein>extracellular and transmembrane regions</protein> but not the <protein>cytoplasmic domain</protein> , was demonstrated by both fluorescence in situ hybridization and genomic Southern blotting .


In most NB cell lines , both the DR3 and the DR3L sequences are simultaneously deleted and/or translocated to another chromosome .

In most <cell_line>NB cell lines</cell_line> , both the <dna>DR3 and the DR3L sequences</dna> are simultaneously deleted and/or translocated to another <dna>chromosome</dna> .


Finally , DR3/ Wsl-1 protein expression is quite variable among these NB cell lines , with very low or undetectable levels in 7 of 17 NB cell lines

Finally , <protein>DR3/ Wsl-1 protein</protein> expression is quite variable among these <cell_line>NB cell lines</cell_line> , with very low or undetectable levels in 7 of 17 <cell_line>NB cell lines</cell_line>


Differential protection of normal and malignant human myeloid progenitors ( CFU-GM ) from Ara-C toxicity using cycloheximide .

Differential protection of <cell_type>normal and malignant human myeloid progenitors</cell_type> ( <cell_type>CFU-GM</cell_type> ) from Ara-C toxicity using cycloheximide .


Cycloheximide , a reversible protein synthesis inhibitor , is thought to block DNA replication in normal cells by preventing synthesis of a labile protein .

Cycloheximide , a reversible protein synthesis inhibitor , is thought to block DNA replication in <cell_type>normal cells</cell_type> by preventing synthesis of a <protein>labile protein</protein> .


In animal systems , cycloheximide protects normal cells from cytotoxic S-phase specific agents , such as cytosine arabinoside ( Ara-C ) .

In animal systems , cycloheximide protects <cell_type>normal cells</cell_type> from cytotoxic S-phase specific agents , such as cytosine arabinoside ( Ara-C ) .


Malignant cells appear not to be susceptible to cycloheximide-induced cycle arrest and , subsequently , may not be protected from Ara-C cytotoxicity .

<cell_type>Malignant cells</cell_type> appear not to be susceptible to cycloheximide-induced cycle arrest and , subsequently , may not be protected from Ara-C cytotoxicity .


The effect of cycloheximide on granulocyte/macrophage progenitors ( CFU-GM ) after in vitro Ara-C exposure was examined using normal human bone marrow , malignant progenitors from patients with chronic myelogenous leukemia ( CML ) , and clonogenic cells from the human acute nonlymphocytic leukemia cell lines HL-60 and KG-1 .

The effect of cycloheximide on <cell_type>granulocyte/macrophage progenitors</cell_type> ( <cell_type>CFU-GM</cell_type> ) after in vitro Ara-C exposure was examined using normal human bone marrow , <cell_type>malignant progenitors</cell_type> from patients with chronic myelogenous leukemia ( CML ) , and <cell_line>clonogenic cells</cell_line> from the <cell_line>human acute nonlymphocytic leukemia cell lines HL-60 and KG-1</cell_line> .


Mononuclear or clonogenic cells were incubated for one hour with cycloheximide , followed by the addition , for three or 17 hours , of Ara-C before being plated in a methylcellulose culture system .

<cell_line>Mononuclear or clonogenic cells</cell_line> were incubated for one hour with cycloheximide , followed by the addition , for three or 17 hours , of Ara-C before being plated in a methylcellulose culture system .


CFU-GM survival was significantly increase if normal cells were treated with cycloheximide before Ara-C exposure .


Similar cycloheximide pretreatment of CML progenitors and clonogenic HL-60 and KG-1 cells failed to protect CFU-GM from Ara-C-induced cytotoxicity .

Similar cycloheximide pretreatment of <cell_type>CML progenitors</cell_type> and <cell_line>clonogenic HL-60 and KG-1 cells</cell_line> failed to protect <cell_type>CFU-GM</cell_type> from Ara-C-induced cytotoxicity .


Primary cortisol resistance accompanied by a reduction in glucocorticoid receptors in two members of the same family .

Primary cortisol resistance accompanied by a reduction in <protein>glucocorticoid receptors</protein> in two members of the same family .


This report describes studies of a man suspected of having primary cortisol resistance .


This conclusion is based on his high plasma cortisol levels and high 24-h urinary 17-hydroxycorticosteroid and cortisol excretion , plus the fact that he had no manifestations of Cushing 's syndrome .


Among family members tested , his mother also had hypercortisolemia .


Both mother and son had high levels of unbound plasma cortisol , but their plasma ACTH concentrations were within the normal range .


Both were partially resistant to dexamethasone adrenal suppression , and both had mild hypertension without hypokalemia .


To study this apparent end-organ resistance to cortisol , we examined the glucocorticoid receptors in peripheral mononuclear cells .

To study this apparent end-organ resistance to cortisol , we examined the <protein>glucocorticoid receptors</protein> in <cell_type>peripheral mononuclear cells</cell_type> .


Using whole cell assays , glucocorticoid receptors in both patients were found to have reduced total binding capacity .

Using whole cell assays , <protein>glucocorticoid receptors</protein> in both patients were found to have reduced total binding capacity .


We conclude that these two patients , members of the same family , have primary cortisol resistance accompanied by a reduced number of glucocorticoid receptors .

We conclude that these two patients , members of the same family , have primary cortisol resistance accompanied by a reduced number of <protein>glucocorticoid receptors</protein> .


[ Glucocorticoid receptors and response to polychemotherapy in acute lymphatic leukemia ]

[ <protein>Glucocorticoid receptors</protein> and response to polychemotherapy in acute lymphatic leukemia ]


Glucocorticoid receptor ( GR ) levels were quantified in leukemic blasts from peripheral blood of 86 patients with acute lymphoblastic leukemia .

<protein>Glucocorticoid receptor</protein> ( <protein>GR</protein> ) levels were quantified in <cell_type>leukemic blasts</cell_type> from peripheral blood of 86 patients with acute lymphoblastic leukemia .


The subsequent achievement of complete remission after combination chemotherapy was correlated with high receptor levels .


Forty-seven of 50 patients with leukemic cells containing more than 6 , 000 receptor sites and 22 of 36 patients with cells containing less than 6 , 000 receptor sites achieved remission .

Forty-seven of 50 patients with <cell_type>leukemic cells</cell_type> containing more than 6 , 000 receptor sites and 22 of 36 patients with cells containing less than 6 , 000 receptor sites achieved remission .


The study of glucocorticoid receptors in leukemic cells may predict response to combination chemotherapy in patients with acute lymphoblastic leukemia .

The study of <protein>glucocorticoid receptors</protein> in <cell_type>leukemic cells</cell_type> may predict response to combination chemotherapy in patients with acute lymphoblastic leukemia .


Specific uptake of 1 , 25-dihydroxycholecalciferol by human chronic myeloid leukemia cells .

Specific uptake of 1 , 25-dihydroxycholecalciferol by <cell_type>human chronic myeloid leukemia cells</cell_type> .


We have examined mononuclear cell preparations from patients with chronic myeloid leukemia [ CML ] for binding of and response to 1 , 25-dihydroxycholecalciferol [ 1 , 25- ( OH ) 2D3 ] .

We have examined <cell_line>mononuclear cell preparations</cell_line> from patients with chronic myeloid leukemia [ CML ] for binding of and response to 1 , 25-dihydroxycholecalciferol [ 1 , 25- ( OH ) 2D3 ] .


Whole cells specifically took up [ 3H ] -1 , 25- ( OH ) 2D3 with high affinity ( Kd 3.6 X 10 ( -11 ) M ) and low capacity .


Subcellular fractionation of labeled cells showed that binding was restricted to cytosols and nuclei .

Subcellular fractionation of <cell_line>labeled cells</cell_line> showed that binding was restricted to cytosols and nuclei .


Sucrose gradient centrifugation of cells preincubated with [ 3H ] -1 , 25- ( OH ) 2D3 revealed a single 3.6S peak which was totally displaced with 100-fold excess nonradioactive hormone .


However , we were unable to demonstrate specific binding of 1 , 25- ( OH ) 2D3 by postlabeling standard cytosol preparations .


In addition , cytosols prepared from a mixture of CML cells and 1 , 25- ( OH ) 2D3 receptor-positive T47D ( human breast cancer ) cells had less than 10 % of the binding measured in T47D cytosol alone .

In addition , cytosols prepared from a mixture of <cell_line>CML cells</cell_line> and <cell_line>1 , 25- ( OH ) 2D3 receptor-positive T47D</cell_line> ( human breast cancer ) cells had less than 10 % of the binding measured in <cell_line>T47D</cell_line> cytosol alone .


However , the levels of binding in T47D cytosols were not reduced if the receptors were occupied with [ 3H ] -1 , 25- ( OH ) 2D3 prior to the addition of the CML cytosols .

However , the levels of binding in <cell_line>T47D</cell_line> cytosols were not reduced if the receptors were occupied with [ 3H ] -1 , 25- ( OH ) 2D3 prior to the addition of the <cell_line>CML</cell_line> cytosols .


Thus , CML cells appear to contain both the receptor for 1 , 25- ( OH ) 2D3 and an unknown substance which prevents its detection following the preparation of cytosol .

Thus , <cell_line>CML cells</cell_line> appear to contain both the receptor for 1 , 25- ( OH ) 2D3 and an unknown substance which prevents its detection following the preparation of cytosol .


Cells from patients with CML in the chronic phase specifically bound more 1 , 25- ( OH ) 2D3 [ 18.0 +/- 3.2 ( S.E. ) fmol/10 ( 7 ) cells ] than did those in acute myeloid transformation [ 7.2 +/- 1.5 ] or than did cells from patients with acute myeloid leukemia [ 2.6 +/- 0.8 ] .


Only cells from the first group of patients responded to the addition of 1 , 25- ( OH ) 2D3 by differentiating along the monocyte-macrophage pathway .


We conclude that the differentiation-induction effect of 1 , 25- ( OH ) 2D3 is likely to depend on adequate levels of receptor and that intact cells rather than cytosol preparations should be studied before cells of a particular tissue are designated as receptor negative .

We conclude that the differentiation-induction effect of 1 , 25- ( OH ) 2D3 is likely to depend on adequate levels of receptor and that <cell_type>intact cells</cell_type> rather than cytosol preparations should be studied before cells of a particular tissue are designated as receptor negative .


Effect of cell cycle position on dexamethasone binding by mouse and human lymphoid cell lines : correlation between an increase in dexamethasone binding during S phase and dexamethasone sensitivity .

Effect of cell cycle position on dexamethasone binding by <cell_line>mouse and human lymphoid cell lines</cell_line> : correlation between an increase in dexamethasone binding during S phase and dexamethasone sensitivity .


We determined the effect of cell cycle position on the amount of dexamethasone that was specifically bound by mouse and human lymphoid cell lines .

We determined the effect of cell cycle position on the amount of dexamethasone that was specifically bound by <cell_line>mouse and human lymphoid cell lines</cell_line> .


Cell lines that were either sensitive or resistant to growth inhibition by dexamethasone were compared .

<cell_line>Cell lines</cell_line> that were either sensitive or resistant to growth inhibition by dexamethasone were compared .


Exponentially growing cells were separated by centrifugal elutriation into fractions that corresponded to different positions in the cell cycle .

<cell_type>Exponentially growing cells</cell_type> were separated by centrifugal elutriation into fractions that corresponded to different positions in the cell cycle .


The cell cycle phase distribution of each fraction was estimated by flow cytometry and autoradiography .


The amount of dexamethasone bound per cell in each fraction was measured by a whole cell binding assay .


In three dexamethasone-sensitive cell lines ( two mouse and one human ) , we found that the amount of dexamethasone bound per cell increased 2-4-fold between G1 phase and S phase , and then decreased during G2/M phase .

In three <cell_line>dexamethasone-sensitive cell lines</cell_line> ( two mouse and one human ) , we found that the amount of dexamethasone bound per cell increased 2-4-fold between G1 phase and S phase , and then decreased during G2/M phase .


Results were the same when the amount of dexamethasone bound per milligram of cell protein was measured .

Results were the same when the amount of dexamethasone bound per milligram of <protein>cell protein</protein> was measured .


Binding affinity was the same during G1 phase and S phase , but the proportion of bound dexamethasone that translocated to the nucleus was greater during S phase .


In contrast , we found that the amount of dexamethasone bound per cell by three dexamethasone-resistant cell lines ( two mouse and one human ) did not increase during S phase .

In contrast , we found that the amount of dexamethasone bound per cell by three <cell_line>dexamethasone-resistant cell lines</cell_line> ( two mouse and one human ) did not increase during S phase .


Our results indicate that cell cycle changes in dexamethasone binding are not simply related to changes in cell protein or cell volume during the cell cycle .

Our results indicate that cell cycle changes in dexamethasone binding are not simply related to changes in <protein>cell protein</protein> or cell volume during the cell cycle .


An increase in dexamethasone binding during S phase may be required for dexamethasone to inhibit cell growth , and a failure of dexamethasone binding to increase during S phase might represent a new mechanism of dexamethasone resistance in lymphoid cells .

An increase in dexamethasone binding during S phase may be required for dexamethasone to inhibit cell growth , and a failure of dexamethasone binding to increase during S phase might represent a new mechanism of dexamethasone resistance in <cell_type>lymphoid cells</cell_type> .


Presence and steroid inducibility of glutamine synthetase in human leukemic cells .

Presence and steroid inducibility of <protein>glutamine synthetase</protein> in <cell_type>human leukemic cells</cell_type> .


Glutamine synthetase ( EC 6.3.1.2 ; GS ) is present in lymphoblasts from patients with acute lymphoblastic leukemia ( ALL ) as well as in normal peripheral blood lymphocytes .

<protein>Glutamine synthetase</protein> ( EC 6.3.1.2 ; GS ) is present in <cell_type>lymphoblasts</cell_type> from patients with acute lymphoblastic leukemia ( ALL ) as well as in <cell_type>normal peripheral blood lymphocytes</cell_type> .


In 16 out of 20 ALL patients studied exposure of the cells to physiological concentrations of dexamethasone in vitro increased enzyme activity above the control levels .

In 16 out of 20 ALL patients studied exposure of the cells to physiological concentrations of dexamethasone in vitro increased <protein>enzyme</protein> activity above the control levels .


The increase was specific for glucocorticoid receptor ligands .

The increase was specific for <protein>glucocorticoid receptor</protein> ligands .


A direct correlation was found between the magnitude of glucocorticoid-mediated increase of GS activity and the cellular levels of specific glucocorticoid receptors assayed in the same cell specimen .

A direct correlation was found between the magnitude of glucocorticoid-mediated increase of GS activity and the cellular levels of specific <protein>glucocorticoid receptors</protein> assayed in the same <cell_type>cell specimen</cell_type> .


Moreover , the basal levels of the enzyme measured in cells prior to exposure to dexamethasone correlated negatively with receptor density .

Moreover , the basal levels of the <protein>enzyme</protein> measured in cells prior to exposure to dexamethasone correlated negatively with receptor density .


It is suggested that the presence of steroid-inducible GS in ALL cells may prove to be a marker for functional receptor sites .

It is suggested that the presence of <protein>steroid-inducible GS</protein> in <cell_type>ALL cells</cell_type> may prove to be a marker for <protein>functional receptor sites</protein> .


Binding of progestins to the glucocorticoid receptor .

Binding of progestins to the <protein>glucocorticoid receptor</protein> .


Correlation to their glucocorticoid-like effects on in vitro functions of human mononuclear leukocytes .

Correlation to their glucocorticoid-like effects on in vitro functions of <cell_type>human mononuclear leukocytes</cell_type> .


A number of physiological and synthetic progestins were tested for their ability to compete with [ 3H ] dexamethasone for the binding to the glucocorticoid receptor of human mononuclear leukocytes and their ability to elicit glucocorticoid-like effects on the same cells .

A number of physiological and synthetic progestins were tested for their ability to compete with [ 3H ] dexamethasone for the binding to the <protein>glucocorticoid receptor</protein> of <cell_type>human mononuclear leukocytes</cell_type> and their ability to elicit glucocorticoid-like effects on the same cells .


As compared to the reference compound dexamethasone ( relative receptor binding affinity defined as 100 % ) , two potent synthetic progestins with a pregnane-type structure , megestrol acetate and medroxyprogesterone acetate , were found to display a considerable binding affinity towards the receptor ( 46 and 42 % , respectively ) .


The relative binding affinity of the naturally occurring ligand , cortisol , to the receptor was clearly lower ( 25 % ) .


The effective binding of medroxyprogesterone acetate to the glucocorticoid receptor was confirmed by direct binding studies utilizing a tritiated derivative of this steroid .

The effective binding of medroxyprogesterone acetate to the <protein>glucocorticoid receptor</protein> was confirmed by direct binding studies utilizing a tritiated derivative of this steroid .