When data obtained preoperatively and after 12 months were compared , it was found that out of 23 patients whose PBMCs had experienced a drop in their PHA -induced proliferation , 14 ( 61 % ) had developed metastatic disease within the subsequent 24 months ( i.e. 36 months after surgery ) .

When data obtained preoperatively and after 12 months were compared , it was found that out of 23 patients whose <cell_type>PBMCs</cell_type> had experienced a drop in their <protein>PHA</protein> -induced proliferation , 14 ( 61 % ) had developed metastatic disease within the subsequent 24 months ( i.e. 36 months after surgery ) .


In contrast , out of 59 patients whose PBMCs showed an increase in their PHA -induced proliferation within the first 12 months after surgery , only one ( 2 % ) presented with disease progression .

In contrast , out of 59 patients whose <cell_type>PBMCs</cell_type> showed an increase in their <protein>PHA</protein> -induced proliferation within the first 12 months after surgery , only one ( 2 % ) presented with disease progression .


We thus conclude that PHA -induced proliferation of PBMCs derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease .

We thus conclude that <protein>PHA</protein> -induced proliferation of <cell_type>PBMCs</cell_type> derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease .


Activation of transcription by binding of NF-E1 ( YY1 ) to a newly identified element in the first exon of the human DR alpha gene .

Activation of transcription by binding of <protein>NF-E1</protein> ( <protein>YY1</protein> ) to a newly identified element in the first exon of the <dna>human DR alpha gene</dna> .


A previously unrecognized element , located downstream of the start site of transcription in the first exon of the DR alpha gene , has been defined that enhances promoter activity up to eightfold in a position-dependent manner .

A previously unrecognized element , located downstream of the <dna>start site of transcription</dna> in the first <dna>exon</dna> of the <dna>DR alpha gene</dna> , has been defined that enhances promoter activity up to eightfold in a position-dependent manner .


Mutations in this DNA-binding site abolished binding of a nuclear factor in human B cell nuclear extract and decreased the activity of the DR alpha promoter to a basal level .

Mutations in this <dna>DNA-binding site</dna> abolished binding of a <protein>nuclear factor</protein> in human B cell nuclear extract and decreased the activity of the <dna>DR alpha promoter</dna> to a basal level .


Significant sequence homology of this element was found in the DNA of the DR beta , DP alpha and -beta , and DQ alpha genes , always located downstream of the transcriptional start site .

Significant sequence homology of this <dna>element</dna> was found in the DNA of the <dna>DR beta , DP alpha and -beta , and DQ alpha genes</dna> , always located downstream of the <dna>transcriptional start site</dna> .


The nuclear factor binds to the DR alpha and DP alpha element but not to the element in the DQ alpha gene .

The nuclear factor binds to the <dna>DR alpha and DP alpha element</dna> but not to the element in the <dna>DQ alpha gene</dna> .


It was identified as NF-E1 ( YY1 ) .

It was identified as <protein>NF-E1</protein> ( <protein>YY1</protein> ) .


This protein , previously identified by its binding to the Ig kappa 3 ' enhancer and the Ig heavy chain mu E1 site , thus also appears to be quite important in the regulation of MHC class II gene expression .

This protein , previously identified by its binding to the <dna>Ig kappa 3 ' enhancer</dna> and the <dna>Ig heavy chain mu E1 site</dna> , thus also appears to be quite important in the regulation of <dna>MHC class II gene</dna> expression .


Transcriptional activity of core binding factor-alpha ( AML1 ) and beta subunits on murine leukemia virus enhancer cores .

Transcriptional activity of <protein>core binding factor-alpha ( AML1 ) and beta</protein> subunits on <dna>murine leukemia virus enhancer cores</dna> .


Core binding factor ( CBF ) , also known as polyomavirus enhancer-binding protein 2 and SL3 enhancer factor 1 , is a mammalian transcription factor that binds to an element termed the core within the enhancers of the murine leukemia virus family of retroviruses .

<protein>Core binding factor</protein> ( <protein>CBF</protein> ) , also known as <protein>polyomavirus enhancer-binding protein 2</protein> and <protein>SL3 enhancer factor 1</protein> , is a <protein>mammalian transcription factor</protein> that binds to an element termed the core within the <dna>enhancers</dna> of the murine leukemia virus family of retroviruses .


The core elements of the SL3 virus are important genetic determinants of the ability of this virus to induce T-cell lymphomas and the transcriptional activity of the viral long terminal repeat in T lymphocytes .

The <dna>core elements</dna> of the SL3 virus are important genetic determinants of the ability of this virus to induce T-cell lymphomas and the transcriptional activity of the <dna>viral long terminal repeat</dna> in <cell_type>T lymphocytes</cell_type> .


CBF consists of two subunits , a DNA binding subunit , CBF alpha , and a second subunit , CBF beta , that stimulates the DNA binding activity of CBF alpha .

<protein>CBF</protein> consists of two subunits , a <protein>DNA binding subunit</protein> , <protein>CBF alpha</protein> , and a second subunit , <protein>CBF beta</protein> , that stimulates the DNA binding activity of <protein>CBF alpha</protein> .


One of the genes that encodes a CBF alpha subunit is AML1 , also called Cbf alpha 2 .

One of the genes that encodes a <protein>CBF alpha subunit</protein> is <protein>AML1</protein> , also called <protein>Cbf alpha 2</protein> .


This locus is rearranged by chromosomal translocations in human myeloproliferative disorders and leukemias .


An exogenously expressed Cbf alpha 2-encoded subunit ( CBF alpha 2-451 ) stimulated transcription from the SL3 enhancer in P19 and HeLa cells .

An exogenously expressed <protein>Cbf alpha 2-encoded subunit</protein> ( <protein>CBF alpha 2-451</protein> ) stimulated transcription from the <dna>SL3 enhancer</dna> in <protein>P19</protein> and <cell_line>HeLa cells</cell_line> .


Activity was mediated through the core elements .

Activity was mediated through the <dna>core elements</dna> .


Three different isoforms of CBF beta were also tested for transcriptional activity on the SL3 enhancer .

Three different isoforms of <protein>CBF beta</protein> were also tested for transcriptional activity on the <dna>SL3 enhancer</dna> .


The longest form , CBF beta-187 , increased the transcriptional stimulation by CBF alpha 2-451 twofold in HeLa cells , although it had no effect in P19 cells .

The longest form , <protein>CBF beta-187</protein> , increased the transcriptional stimulation by <protein>CBF alpha 2-451</protein> twofold in <cell_line>HeLa cells</cell_line> , although it had no effect in <cell_line>P19 cells</cell_line> .


Transcriptional activation by CBF beta required binding to the CBF alpha subunit , as a form of CBF beta that lacked binding ability , CBF beta-148 , failed to increase activity .

Transcriptional activation by <protein>CBF beta</protein> required binding to the <protein>CBF alpha subunit</protein> , as a form of <protein>CBF beta</protein> that lacked binding ability , <protein>CBF beta-148</protein> , failed to increase activity .


These results indicated that at least in certain cell types , the maximum activity of CBF required both subunits .

These results indicated that at least in certain cell types , the maximum activity of <protein>CBF</protein> required both subunits .


They also provided support for the hypothesis that CBF is a factor in T lymphocytes that is responsible for recognition of the SL3 cores .

They also provided support for the hypothesis that <protein>CBF</protein> is a factor in <cell_type>T lymphocytes</cell_type> that is responsible for recognition of the <dna>SL3 cores</dna> .


We also examined whether CBF could distinguish a 1-bp difference between the enhancer core of SL3 and the core of the nonleukemogenic virus , Akv .

We also examined whether <protein>CBF</protein> could distinguish a 1-bp difference between the enhancer core of SL3 and the core of the nonleukemogenic virus , Akv .


This difference strongly affects transcription in T cells and leukemogenicity of SL3 .

This difference strongly affects transcription in T cells and leukemogenicity of <dna>SL3</dna> .


However , no combination of CBF alpha and CBF beta subunits that we tested was able to distinguish the 1-bp difference in transcription assays .

However , no combination of <protein>CBF alpha</protein> and <protein>CBF beta</protein> subunits that we tested was able to distinguish the 1-bp difference in transcription assays .


Thus , a complete understanding of how T cells recognize the SL3 core remains to be elucidated .

Thus , a complete understanding of how <cell_type>T cells</cell_type> recognize the <dna>SL3 core</dna> remains to be elucidated .


Interleukin ( IL ) -10 inhibits nuclear factor kappa B ( NF kappa B ) activation in human monocytes .

<protein>Interleukin ( IL ) -10</protein> inhibits <protein>nuclear factor kappa B</protein> ( <protein>NF kappa B</protein> ) activation in <cell_type>human monocytes</cell_type> .


IL-10 and IL-4 suppress cytokine synthesis by different mechanisms .

<protein>IL-10</protein> and <protein>IL-4</protein> suppress <protein>cytokine</protein> synthesis by different mechanisms .


Our previous studies in human monocytes have demonstrated that interleukin ( IL ) -10 inhibits lipopolysaccharide ( LPS ) -stimulated production of inflammatory cytokines , IL-1 beta , IL-6 , IL-8 , and tumor necrosis factor ( TNF ) -alpha by blocking gene transcription .

Our previous studies in <cell_type>human monocytes</cell_type> have demonstrated that <protein>interleukin ( IL ) -10</protein> inhibits lipopolysaccharide ( LPS ) -stimulated production of <protein>inflammatory cytokines</protein> , <protein>IL-1 beta</protein> , <protein>IL-6</protein> , <protein>IL-8</protein> , and <protein>tumor necrosis factor ( TNF ) -alpha</protein> by blocking gene transcription .


Using electrophoretic mobility shift assays ( EMSA ) , we now show that , in monocytes stimulated with LPS or TNF alpha , IL-10 inhibits nuclear stimulation of nuclear factor kappa B ( NF kappa B ) , a transcription factor involved in the expression of inflammatory cytokine genes . Several other transcription factors including NF- IL-6 , AP-1 , AP-2 , GR , CREB , Oct-1 , and Sp-1 are not affected by IL-10 .

Using electrophoretic mobility shift assays ( EMSA ) , we now show that , in monocytes stimulated with LPS or <protein>TNF alpha</protein> , <protein>IL-10</protein> inhibits nuclear stimulation of <protein>nuclear factor kappa B</protein> ( <protein>NF kappa B</protein> ) , a <protein>transcription factor</protein> involved in the expression of <dna>inflammatory cytokine genes</dna> . Several other <protein>transcription factors</protein> including NF- <protein>IL-6</protein> , <protein>AP-1</protein> , <protein>AP-2</protein> , <protein>GR</protein> , <protein>CREB</protein> , <protein>Oct-1</protein> , and <protein>Sp-1</protein> are not affected by <protein>IL-10</protein> .


This selective inhibition by IL-10 of NF kappa B activation occurs rapidly and in a dose-dependent manner and correlates well with IL-10 's cytokine synthesis inhibitory activity in terms of both kinetics and dose responsiveness .

This selective inhibition by <protein>IL-10</protein> of <protein>NF kappa B</protein> activation occurs rapidly and in a dose-dependent manner and correlates well with <protein>IL-10</protein> 's <protein>cytokine</protein> synthesis inhibitory activity in terms of both kinetics and dose responsiveness .


Furthermore , compounds such as tosylphenylalanyl chloromethyl ketone and pyrrolidinedithiocarbamate that are known to selectively inhibit NF kappa B activation block cytokine gene transcription in LPS-stimulated monocytes .

Furthermore , compounds such as tosylphenylalanyl chloromethyl ketone and pyrrolidinedithiocarbamate that are known to selectively inhibit <protein>NF kappa B</protein> activation block cytokine gene transcription in <cell_line>LPS-stimulated monocytes</cell_line> .


Taken together , these results suggest that inhibition of NF kappa B activation may be an important mechanism for IL-10 suppression of cytokine gene transcription in human monocytes .

Taken together , these results suggest that inhibition of <protein>NF kappa B</protein> activation may be an important mechanism for <protein>IL-10</protein> suppression of cytokine gene transcription in <cell_type>human monocytes</cell_type> .


IL-4 , another cytokine that inhibits cytokine mRNA accumulation in monocytes , shows little inhibitory effect on LPS-induced NF kappa B activation .

<protein>IL-4</protein> , another <protein>cytokine</protein> that inhibits <rna>cytokine mRNA</rna> accumulation in <cell_type>monocytes</cell_type> , shows little inhibitory effect on LPS-induced <protein>NF kappa B</protein> activation .


Further examination reveals that , unlike IL-10 , IL-4 enhances mRNA degradation and does not suppress cytokine gene transcription .

Further examination reveals that , unlike <protein>IL-10</protein> , <protein>IL-4</protein> enhances <rna>mRNA</rna> degradation and does not suppress cytokine gene transcription .


These data indicate that IL-10 and IL-4 inhibit cytokine production by different mechanisms .

These data indicate that <protein>IL-10</protein> and <protein>IL-4</protein> inhibit <protein>cytokine</protein> production by different mechanisms .


LMP-1 activates NF-kappa B by targeting the inhibitory molecule I kappa B alpha .

<protein>LMP-1</protein> activates <protein>NF-kappa B</protein> by targeting the <protein>inhibitory molecule I kappa B alpha</protein> .


LMP-1 , an Epstein-Barr virus membrane protein expressed during latent infection , has oncogenic properties , as judged from its ability to transform B lymphocytes and rodent fibroblasts .

<protein>LMP-1</protein> , an <protein>Epstein-Barr virus membrane protein</protein> expressed during latent infection , has oncogenic properties , as judged from its ability to transform B <cell_type>lymphocytes</cell_type> and <cell_type>rodent fibroblasts</cell_type> .


LMP-1 induces the expression of bcl2 , an oncogene which protects cells from apoptosis , as well as of genes encoding other proteins involved in cell regulation and growth control .

<protein>LMP-1</protein> induces the expression of <dna>bcl2</dna> , an <dna>oncogene</dna> which protects cells from apoptosis , as well as of genes encoding other proteins involved in cell regulation and growth control .


The mechanisms by which LMP-1 upregulates these proteins is unknown , but it is plausible that LMP-1 modifies signal transduction pathways that result in the activation of one or more transcription factors that ultimately regulate transcription of oncogenic genes .

The mechanisms by which <protein>LMP-1</protein> upregulates these proteins is unknown , but it is plausible that <protein>LMP-1</protein> modifies signal transduction pathways that result in the activation of one or more <protein>transcription factors</protein> that ultimately regulate transcription of <dna>oncogenic genes</dna> .


NF-kappa B , a transcription factor controlling the expression of genes involved in cell activation and growth control , has been shown to be activated by LMP-1 .

<protein>NF-kappa B</protein> , a <protein>transcription factor</protein> controlling the expression of <dna>genes</dna> involved in cell activation and growth control , has been shown to be activated by <protein>LMP-1</protein> .


The mechanism ( s ) regulating this activation remains unknown .


Our data indicate that increased NF-kappa B DNA binding and functional activity are present in B-lymphoid cells stably or transiently expressing LMP-1 .

Our data indicate that increased <protein>NF-kappa B</protein> DNA binding and functional activity are present in <cell_type>B-lymphoid cells</cell_type> stably or transiently expressing <protein>LMP-1</protein> .


I kappa B alpha is selectively modified in LMP-1-expressing B cells .

<protein>I kappa B alpha</protein> is selectively modified in <cell_line>LMP-1-expressing B cells</cell_line> .


A phosphorylated form of I kappa B alpha and increased protein turnover-degradation correlate with increased NF-kappa B nuclear translocation .

A phosphorylated form of <protein>I kappa B alpha</protein> and increased protein turnover-degradation correlate with increased <protein>NF-kappa B</protein> nuclear translocation .


This results in increased transcription of NF-kappa B-dependent-genes , including those encoding p105 and I kappa B alpha ( MAD3 ) .

This results in increased transcription of <dna>NF-kappa B-dependent-genes</dna> , including those encoding <protein>p105</protein> and <protein>I kappa B alpha</protein> ( <dna>MAD3</dna> ) .


These results indicate that LMP-1 activates NF-kappa B in B-cell lines by targeting I kappa B alpha .

These results indicate that <protein>LMP-1</protein> activates <protein>NF-kappa B</protein> in <cell_line>B-cell lines</cell_line> by targeting <protein>I kappa B alpha</protein> .


Identification of the pathways activated by LMP-1 to result in posttranslational modifications of I kappa B alpha will aid in determining the role of this virus-host cell protein interaction in Epstein-Barr virus-mediated oncogenesis .

Identification of the pathways activated by <protein>LMP-1</protein> to result in posttranslational modifications of <protein>I kappa B alpha</protein> will aid in determining the role of this virus-host cell protein interaction in Epstein-Barr virus-mediated oncogenesis .


Identification of human TR2 orphan receptor response element in the transcriptional initiation site of the simian virus 40 major late promoter [ published erratum appears in J Biol Chem 1995 Nov 3 ; 270 ( 44 ) : 26721 ]

Identification of <dna>human TR2 orphan receptor response element</dna> in the <dna>transcriptional initiation site</dna> of the <dna>simian virus 40 major late promoter</dna> [ published erratum appears in J Biol Chem 1995 Nov 3 ; 270 ( 44 ) : 26721 ]


A DNA response element ( TR2RE-SV40 ) for the TR2 orphan receptor , a member of the steroid-thyroid hormone receptor superfamily , has been identified in the simian virus 40 ( SV40 ) +55 region ( nucleotide numbers 368-389 , 5'-GTTAAGGTTCGTAGGTCATGGA-3 ' ) .

A <dna>DNA response element</dna> ( <dna>TR2RE-SV40</dna> ) for the <protein>TR2 orphan receptor</protein> , a member of the <protein>steroid-thyroid hormone receptor superfamily</protein> , has been identified in the <dna>simian virus 40 ( SV40 ) +55 region</dna> ( <dna>nucleotide numbers 368-389</dna> , 5'-GTTAAGGTTCGTAGGTCATGGA-3 ' ) .


Electrophoretic mobility shift assay , using in vitro translated TR2 orphan receptor with a molecular mass of 67 kilodaltons , showed a specific binding with high affinity ( dissociation constant = 9 nM ) for this DNA sequence .

Electrophoretic mobility shift assay , using in vitro translated <protein>TR2 orphan receptor</protein> with a molecular mass of <protein>67 kilodaltons</protein> , showed a specific binding with high affinity ( dissociation constant = 9 nM ) for this DNA sequence .


DNA-swap experiments using chloramphenicol acetyl-transferase assay demonstrated that androgen can suppress the transcriptional activities of SV40 early promoter via the interaction between this TR2RE-SV40 and the chimeric receptor AR/TR2/AR with the DNA-binding domain of the TR2 orphan receptor flanked by the N-terminal and androgen-binding domains of the androgen receptor .

DNA-swap experiments using <protein>chloramphenicol acetyl-transferase</protein> assay demonstrated that androgen can suppress the transcriptional activities of <dna>SV40 early promoter</dna> via the interaction between this <dna>TR2RE-SV40</dna> and the <protein>chimeric receptor AR/TR2/AR</protein> with the <protein>DNA-binding domain</protein> of the <protein>TR2 orphan receptor</protein> flanked by the <protein>N-terminal and androgen-binding domains</protein> of the <protein>androgen receptor</protein> .


In addition , this TR2RE-SV40 can function as a repressor to suppress the transcriptional activities of both SV40 early and late promoters .

In addition , this <dna>TR2RE-SV40</dna> can function as a repressor to suppress the transcriptional activities of both <dna>SV40 early and late promoters</dna> .


Together , these data suggest the TR2RE-SV40 may represent the first identified natural DNA response element for the TR2 orphan receptor that may function as a repressor for the SV40 gene expression .

Together , these data suggest the <dna>TR2RE-SV40</dna> may represent the first identified natural <dna>DNA response element</dna> for the <protein>TR2 orphan receptor</protein> that may function as a repressor for the SV40 gene expression .


Detection of the chromosome 16 CBF beta-MYH11 fusion transcript in myelomonocytic leukemias .

Detection of the <rna>chromosome 16 CBF beta-MYH11 fusion transcript</rna> in myelomonocytic leukemias .


Karyotypic detection of chromosomal 16 abnormalities classically associated with AML M4Eo can be difficult .


Characterization of the two genes involved in the inv ( 16 ) ( p13q22 ) , CBF beta and MYH11 , has allowed the detection of fusion transcripts by reverse-transcriptase polymerase chain reaction ( RT-PCR ) .

Characterization of the two genes involved in the inv ( 16 ) ( p13q22 ) , <dna>CBF beta</dna> and <dna>MYH11</dna> , has allowed the detection of <rna>fusion transcripts</rna> by reverse-transcriptase polymerase chain reaction ( RT-PCR ) .


We have analyzed CBF beta-MYH11 fusion transcripts by RT-PCR in myelomonocytic leukemias , with or without eosinophilia , to determine whether their presence correlates with morphology .

We have analyzed <rna>CBF beta-MYH11 fusion transcripts</rna> by RT-PCR in myelomonocytic leukemias , with or without eosinophilia , to determine whether their presence correlates with morphology .


Fifty-three cases ( 11 AML M4Eo ; 1 AML M4 with atypical abnormal eosinophils ( AML M4 `` Eo '' ) ; 29 AML M4 ; 8 AML M5 ; 3 CMML ; and 1 AML M2 with eosinophilia ) were analyzed .

Fifty-three cases ( 11 AML M4Eo ; 1 AML M4 with <cell_type>atypical abnormal eosinophils</cell_type> ( AML M4 `` Eo '' ) ; 29 AML M4 ; 8 AML M5 ; 3 CMML ; and 1 AML M2 with eosinophilia ) were analyzed .


All 11 typical AML M4Eo were CBF beta -MYH11 positive .

All 11 typical AML M4Eo were <dna>CBF beta</dna> <dna>-MYH11</dna> positive .


The single case of AML M4 with distinctive eosinophil abnormalities was negative by karyotype , RT-PCR and fluorescent in situ hybridization ( FISH ) .


Three of 29 ( 10 % ) AML M4 without abnormal eosinophils were CBF beta -MYH11 positive , 1 of which did not show any apparent chromosome 16 abnormalities by classical metaphase analysis ( 2 not tested ) .

Three of 29 ( 10 % ) AML M4 without <cell_type>abnormal eosinophils</cell_type> were <dna>CBF beta</dna> <dna>-MYH11</dna> positive , 1 of which did not show any apparent <dna>chromosome 16</dna> abnormalities by classical metaphase analysis ( 2 not tested ) .


Both cases tested also showed MYH11 genomic rearrangement .

Both cases tested also showed <dna>MYH11</dna> genomic rearrangement .


of the other leukemias were RT-PCR positive .


Follow-up of three patient showed residual positivity in apparent complete remission .


These data show that CBF beta-MYH11 fusion transcripts occur not only in the vast majority of typical AML M4Eo , but also in approximately 10 % of AML M4 without eosinophilic abnormalities , a much higher incidence than the sporadic reports of chromosome 16 abnormalities in AML M4 would suggest .

These data show that <rna>CBF beta-MYH11 fusion transcripts</rna> occur not only in the vast majority of typical AML M4Eo , but also in approximately 10 % of AML M4 without eosinophilic abnormalities , a much higher incidence than the sporadic reports of <dna>chromosome 16</dna> abnormalities in AML M4 would suggest .


Taken together with the detection of CBF beta - MYH11 transcripts in the absence of apparent chromosome 16 abnormalities by classical banding techniques , these data show that additional screening by either RT-PCR or FISH should be performed in all AML M4 , regardless of morphologic features , to allow accurate evaluation of the prognostic importance of this fusion transcript .

Taken together with the detection of <dna>CBF beta</dna> - <rna>MYH11 transcripts</rna> in the absence of apparent <dna>chromosome 16</dna> abnormalities by classical banding techniques , these data show that additional screening by either RT-PCR or FISH should be performed in all AML M4 , regardless of morphologic features , to allow accurate evaluation of the prognostic importance of this <rna>fusion transcript</rna> .


HIV-1 Tat potentiates TNF -induced NF-kappa B activation and cytotoxicity by altering the cellular redox state .

<protein>HIV-1 Tat</protein> potentiates <protein>TNF</protein> -induced <protein>NF-kappa B</protein> activation and cytotoxicity by altering the cellular redox state .


This study demonstrates that human immunodeficiency virus type 1 ( HIV-1 ) Tat protein amplifies the activity of tumor necrosis factor ( TNF ) , a cytokine that stimulates HIV-1 replication through activation of NF-kappa B .

This study demonstrates that <protein>human immunodeficiency virus type 1 ( HIV-1 ) Tat protein</protein> amplifies the activity of <protein>tumor necrosis factor</protein> ( <protein>TNF</protein> ) , a cytokine that stimulates HIV-1 replication through activation of <protein>NF-kappa B</protein> .


In HeLa cells stably transfected with the HIV-1 tat gene ( HeLa-tat cells ) , expression of the Tat protein enhanced both TNF -induced activation of NF-kappa B and TNF -mediated cytotoxicity .

In <cell_line>HeLa cells</cell_line> stably transfected with the <dna>HIV-1 tat gene</dna> ( <cell_line>HeLa-tat cells</cell_line> ) , expression of the <protein>Tat protein</protein> enhanced both <protein>TNF</protein> -induced activation of <protein>NF-kappa B</protein> and <protein>TNF</protein> -mediated cytotoxicity .


A similar potentiation of TNF effects was observed in Jurkat T cells and HeLa cells treated with soluble Tat protein .

A similar potentiation of <protein>TNF</protein> effects was observed in Jurkat T cells and <cell_line>HeLa cells</cell_line> treated with soluble <protein>Tat protein</protein> .


TNF -mediated activation of NF-kappa B and cytotoxicity involves the intracellular formation of reactive oxygen intermediates .

<protein>TNF</protein> -mediated activation of <protein>NF-kappa B</protein> and cytotoxicity involves the intracellular formation of reactive oxygen intermediates .


Therefore , Tat -mediated effects on the cellular redox state were analyzed .

Therefore , <protein>Tat</protein> -mediated effects on the cellular redox state were analyzed .


In both T cells and HeLa cells HIV-1 Tat suppressed the expression of Mn-dependent superoxide dismutase ( Mn-SOD ) , a mitochondrial enzyme that is part of the cellular defense system against oxidative stress .

In both <cell_type>T cells</cell_type> and <cell_line>HeLa cells</cell_line> <protein>HIV-1 Tat</protein> suppressed the expression of <protein>Mn-dependent superoxide dismutase</protein> ( <protein>Mn-SOD</protein> ) , a <protein>mitochondrial enzyme</protein> that is part of the cellular defense system against oxidative stress .


Thus , Mn-SOD RNA protein levels and activity were markedly reduced in the presence of Tat .

Thus , <protein>Mn-SOD</protein> RNA protein levels and activity were markedly reduced in the presence of <protein>Tat</protein> .


Decreased Mn-SOD expression was associated with decreased levels of glutathione and a lower ratio of reduced : oxidized glutathione .

Decreased <protein>Mn-SOD</protein> expression was associated with decreased levels of glutathione and a lower ratio of reduced : oxidized glutathione .


A truncated Tat protein ( Tat1-72 ) , known to transactivate the HIV-1 long terminal repeat ( LTR ) , no longer affected Mn-SOD expression , the cellular redox state or TNF -mediated cytotoxicity .

A truncated <protein>Tat protein</protein> ( <protein>Tat1-72</protein> ) , known to transactivate the <dna>HIV-1 long terminal repeat</dna> ( <dna>LTR</dna> ) , no longer affected <protein>Mn-SOD</protein> expression , the cellular redox state or <protein>TNF</protein> -mediated cytotoxicity .


Thus , our experiments demonstrate that the C-terminal region of HIV-1 Tat is required to suppress Mn-SOD expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione ( GSH ) and the GSH : oxidized GSH ( GSSG ) ratio .

Thus , our experiments demonstrate that the <protein>C-terminal region</protein> of <protein>HIV-1 Tat</protein> is required to suppress <protein>Mn-SOD</protein> expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione ( <protein>GSH</protein> ) and the GSH : oxidized GSH ( GSSG ) ratio .


( ABSTRACT TRUNCATED AT 250 WORDS )


The use of glucocorticoids in acute lymphoblastic leukemia of childhood .


Molecular , cellular , and clinical considerations .


Glucocorticoids have been included in almost all treatment regimens for childhood acute lymphoblastic leukemia for decades .


However , optimal agents , doses , and/or schedules have yet to be defined despite extensive clinical application .


New data on the pharmacokinetics , pharmacodynamics , and molecular mechanisms of action of glucocorticoids have suggested alternative approaches in ALL .


These suggest that prolonged , i.e. 28 day , glucocorticoid therapy may be unnecessary as exposure to glucocorticoid induces down-regulation of glucocorticoid receptors .

These suggest that prolonged , i.e. 28 day , glucocorticoid therapy may be unnecessary as exposure to glucocorticoid induces down-regulation of <protein>glucocorticoid receptors</protein> .


Dexamethasone may be superior to prednisone in conventional equi-effective doses .


Blast sensitivity to glucocorticoids correlates closely with sensitivity to other , putatively non-cross-resisting agents and with outcome after multi-agent therapy , suggesting overlapping mechanisms of action , and focusing attention on the determinants of the threshold for apoptosis .


Increasing success in the treatment of childhood acute lymphoblastic leukemia has led to increasing awareness of avascular necrosis of bone as a potentially disabling sequela of glucocorticoid therapy , especially in adolescent and young adult patients .


Epstein-Barr virus nuclear protein 2 transactivation of the latent membrane protein 1 promoter is mediated by J kappa and PU.1 .

<protein>Epstein-Barr virus nuclear protein 2</protein> transactivation of the <dna>latent membrane protein 1 promoter</dna> is mediated by <protein>J kappa</protein> and <protein>PU.1</protein> .


Expression of the Epstein-Barr virus ( EBV ) latent membrane protein 1 ( LMP-1 ) oncogene is regulated by the EBV nuclear protein 2 ( EBNA-2 ) transactivator .

Expression of the <dna>Epstein-Barr virus ( EBV ) latent membrane protein 1 ( LMP-1 ) oncogene</dna> is regulated by the <protein>EBV nuclear protein 2 ( EBNA-2 ) transactivator</protein> .


EBNA-2 is known to interact with the cellular DNA-binding protein J kappa and is recruited to promoters containing the GTGGGAA J kappa recognition sequence .

<protein>EBNA-2</protein> is known to interact with the <protein>cellular DNA-binding protein</protein> <protein>J kappa</protein> and is recruited to <dna>promoters</dna> containing the GTGGGAA <dna>J kappa recognition sequence</dna> .


The minimal EBNA-2-responsive LMP-1 promoter includes one J kappa-binding site , and we now show that mutation of that site , such that J kappa can not bind , reduces EBNA-2 responsiveness by 60 % .

The <dna>minimal EBNA-2-responsive LMP-1 promoter</dna> includes one <dna>J kappa-binding site</dna> , and we now show that mutation of that site , such that <protein>J kappa</protein> can not bind , reduces <protein>EBNA-2</protein> responsiveness by 60 % .


To identify other factors which interact with the LMP-1 EBNA-2 response element ( E2RE ) , a -236/-145 minimal E2RE was used as a probe in an electrophoretic mobility shift assay .

To identify other factors which interact with the <dna>LMP-1 EBNA-2 response element</dna> ( <dna>E2RE</dna> ) , a <dna>-236/-145 minimal E2RE</dna> was used as a probe in an electrophoretic mobility shift assay .


The previously characterized factors J kappa , PU.1 , and AML1 bind to the LMP-1 E2RE , along with six other unidentified factors ( LBF2 to LBF7 ) .

The previously characterized factors <protein>J kappa</protein> , <protein>PU.1</protein> , and <protein>AML1</protein> bind to the <dna>LMP-1 E2RE</dna> , along with six other unidentified factors ( <protein>LBF2</protein> to <protein>LBF7</protein> ) .


Binding sites were mapped for each factor .


LBF4 is B- and T-cell specific and recognizes the PU.1 GGAA core sequence as shown by methylation interference .

<protein>LBF4</protein> is B- and T-cell specific and recognizes the <dna>PU.1 GGAA core sequence</dna> as shown by methylation interference .


LBF4 has a molecular mass of 105 kDa and is probably unrelated to PU.1 .

<protein>LBF4</protein> has a molecular mass of 105 kDa and is probably unrelated to <protein>PU.1</protein> .


LBF2 was found only in epithelial cell lines , whereas LBF3 , LBF5 , LBF6 , and LBF7 were not cell type specific .

<protein>LBF2</protein> was found only in <cell_line>epithelial cell lines</cell_line> , whereas <protein>LBF3</protein> , <protein>LBF5</protein> , <protein>LBF6</protein> , and <protein>LBF7</protein> were not cell type specific .


Mutations of the AML1- or LBF4-binding sites had no effect on EBNA-2 transactivation , whereas mutation of the PU.1-binding site completely eliminated EBNA-2 responses .

Mutations of the <dna>AML1- or LBF4-binding sites</dna> had no effect on <protein>EBNA-2</protein> transactivation , whereas mutation of the <dna>PU.1-binding site</dna> completely eliminated <protein>EBNA-2</protein> responses .


A gst-EBNA-2 fusion protein specifically depleted PU.1 from nuclear extracts and bound in vitro translated PU.1 , providing biochemical evidence for a direct EBNA-2 -PU.1 interaction .

A <protein>gst-EBNA-2 fusion protein</protein> specifically depleted <protein>PU.1</protein> from nuclear extracts and bound in vitro translated <protein>PU.1</protein> , providing biochemical evidence for a direct <protein>EBNA-2</protein> <protein>-PU.1</protein> interaction .


Thus , EBNA-2 transactivation of the LMP-1 promoter is dependent on interaction with at least two distinct sequence-specific DNA-binding proteins , J kappa and PU.1 .

Thus , <protein>EBNA-2</protein> transactivation of the <dna>LMP-1 promoter</dna> is dependent on interaction with at least two distinct sequence-specific <protein>DNA-binding proteins</protein> , <protein>J kappa</protein> and <protein>PU.1</protein> .


LBF3 , LBF5 , LBF6 , or LBF7 may also be involved , since their binding sites also contribute to EBNA-2 responsiveness .

<protein>LBF3</protein> , <protein>LBF5</protein> , <protein>LBF6</protein> , or <protein>LBF7</protein> may also be involved , since their binding sites also contribute to <protein>EBNA-2</protein> responsiveness .


Lymphocyte glucocorticoid receptor : predictor of sertraline response in adolescent major depressive disorder ( MDD ) .

<protein>Lymphocyte glucocorticoid receptor</protein> : predictor of sertraline response in adolescent major depressive disorder ( MDD ) .


Major depressive disorder ( MDD ) in adolescents demonstrates resistance to tricyclic antidepressants and absence of hypercortisolemia .


The efficacy of serotonin reuptake inhibitors ( SRIs ) is uncertain , and response predictors are unavailable .


Abnormal fast feedback and negative feedback of the hypothalamic-pituitary-adrenal axis implicates a dampened limbic-hippocampal glucocorticoid type II receptor ( GCII ) .

Abnormal fast feedback and negative feedback of the hypothalamic-pituitary-adrenal axis implicates a dampened <protein>limbic-hippocampal glucocorticoid type II receptor</protein> ( <protein>GCII</protein> ) .


We hypothesized that lymphocyte GCII is altered in adolescent MDD and could serve as a marker for response to SRIs .

We hypothesized that <protein>lymphocyte GCII</protein> is altered in adolescent MDD and could serve as a marker for response to SRIs .


In an open-label study , adolescents ( n = 20 ) meeting DSM-III-R criteria for MDD showed baseline lymphocyte GCII sites per cell ( sites/cell ) values of 793 +/- 106 versus 2 , 563 +/- 499 ( +/- SEM ) for matched controls ( n = 18 ) ( t = 3.5 ; df = 36 ; p < .001 ) .

In an open-label study , adolescents ( n = 20 ) meeting DSM-III-R criteria for MDD showed baseline <protein>lymphocyte GCII sites</protein> per cell ( sites/cell ) values of 793 +/- 106 versus 2 , 563 +/- 499 ( +/- SEM ) for matched controls ( n = 18 ) ( t = 3.5 ; df = 36 ; p < .001 ) .


GCII was bimodally distributed , with SRI responders differing from nonresponders ( t = 3.9 ; df = 14 ; p < .001 ) .

<protein>GCII</protein> was bimodally distributed , with SRI responders differing from nonresponders ( t = 3.9 ; df = 14 ; p < .001 ) .


GCII accurately classified 90 percent of sertraline responders and 80 percent of nonresponders .

<protein>GCII</protein> accurately classified 90 percent of sertraline responders and 80 percent of nonresponders .


Only SRI responders showed GCII sites/cell upregulated after 6 weeks of treatment ( t = 2.1 , df = 10 ; p < .05 ) .

Only SRI responders showed <protein>GCII</protein> sites/cell upregulated after 6 weeks of treatment ( t = 2.1 , df = 10 ; p < .05 ) .


The role of NFATp in cyclosporin A-sensitive tumor necrosis factor-alpha gene transcription .

The role of <protein>NFATp</protein> in <dna>cyclosporin A-sensitive tumor necrosis factor-alpha gene</dna> transcription .


The tumor necrosis factor-alpha ( TNF alpha ) gene is an immediate early gene in activated T cells , in that it is rapidly induced without a requirement for protein synthesis .

The <dna>tumor necrosis factor-alpha ( TNF alpha ) gene</dna> is an immediate early gene in activated <cell_type>T cells</cell_type> , in that it is rapidly induced without a requirement for protein synthesis .


Maximal induction of TNF alpha mRNA can be induced by treatment of T cells with calcium ionophores alone , via a calcineurin -dependent process that is blocked by cyclosporin A .

Maximal induction of <rna>TNF alpha mRNA</rna> can be induced by treatment of <cell_type>T cells</cell_type> with calcium ionophores alone , via a <protein>calcineurin</protein> -dependent process that is blocked by cyclosporin A .


We have previously identified a promoter element , kappa 3 , that is required for calcium-stimulated , cyclosporin A-sensitive induction of the TNF alpha gene in activated T cells .

We have previously identified a <dna>promoter element</dna> , <dna>kappa 3</dna> , that is required for calcium-stimulated , cyclosporin A-sensitive induction of the <dna>TNF alpha gene</dna> in activated <cell_type>T cells</cell_type> .


Here , we demonstrate that the kappa 3 binding factor contains NFATp , a cyclosporin-sensitive DNA-binding protein required for interleukin-2 gene transcription .

Here , we demonstrate that the <protein>kappa 3 binding factor</protein> contains <protein>NFATp</protein> , a <protein>cyclosporin-sensitive DNA-binding protein</protein> required for <dna>interleukin-2 gene</dna> transcription .


NFATp binds to two sites within the kappa 3 element , and occupancy of both sites is required for TNF alpha gene induction .

<protein>NFATp</protein> binds to two sites within the <dna>kappa 3 element</dna> , and occupancy of both sites is required for <protein>TNF</protein> alpha gene induction .


Thus , although the kappa 3 element has little sequence similarity to other NFATp-binding sites , it appears to function as a cyclosporin-sensitive promoter element in T cells by virtue of its ability to bind NFATp .

Thus , although the <dna>kappa 3 element</dna> has little sequence similarity to other <dna>NFATp-binding sites</dna> , it appears to function as a <dna>cyclosporin-sensitive promoter element</dna> in <cell_type>T cells</cell_type> by virtue of its ability to bind <protein>NFATp</protein> .


The involvement of NFATp in transcriptional activation of both the interleukin-2 and TNF alpha genes suggests that this factor plays an important role in the coordinate induction of multiple cytokine genes , starting at the earliest stages of T cell activation .

The involvement of <protein>NFATp</protein> in transcriptional activation of both the <protein>interleukin-2</protein> and <dna>TNF alpha genes</dna> suggests that this factor plays an important role in the coordinate induction of multiple <dna>cytokine genes</dna> , starting at the earliest stages of T cell activation .


Regulation and specificity of MNDA expression in monocytes , macrophages , and leukemia/B lymphoma cell lines .

Regulation and specificity of <protein>MNDA</protein> expression in <cell_type>monocytes</cell_type> , <cell_type>macrophages</cell_type> , and <cell_line>leukemia/B lymphoma cell lines</cell_line> .


The expression of the human myeloid cell nuclear differentiation antigen ( MNDA ) was observed specifically in cells of the granulocyte-macrophage lineage in our earlier reports .

The expression of the <protein>human myeloid cell nuclear differentiation antigen</protein> ( <protein>MNDA</protein> ) was observed specifically in cells of the granulocyte-macrophage lineage in our earlier reports .


The specificity of MNDA expression for cells in the granulocyte-macrophage lineage was reexamined in cell lines established from patients with Philadelphia chromosome-positive chronic myeloid leukemia .

The specificity of <protein>MNDA</protein> expression for cells in the granulocyte-macrophage lineage was reexamined in <cell_line>cell lines</cell_line> established from patients with Philadelphia chromosome-positive chronic myeloid leukemia .


Cell lines that expressed MNDA exhibited myeloid cell features and granulocyte or monocyte differentiation could be induced in vitro , while cell lines exhibiting properties of very early stage cells or multipotential cells did not express MNDA .

Cell lines that expressed <protein>MNDA</protein> exhibited myeloid cell features and granulocyte or monocyte differentiation could be induced in vitro , while cell lines exhibiting properties of very early stage cells or <cell_type>multipotential cells</cell_type> did not express <protein>MNDA</protein> .


Cells originating from cases of Burkitt 's lymphoma were negative .


By contrast , three lymphoblastoid cell lines ( immortalized in vitro with Epstein-Barr virus ) were weakly positive and MNDA was up-regulated by interferon-alpha ( IFN-alpha ) treatment .

By contrast , three <cell_line>lymphoblastoid cell lines</cell_line> ( immortalized in vitro with Epstein-Barr virus ) were weakly positive and <protein>MNDA</protein> was up-regulated by <protein>interferon-alpha</protein> ( <protein>IFN-alpha</protein> ) treatment .


As we reported previously , MNDA mRNA level in adherent monocytes is elevated by IFN-alpha ; in this study , we further assessed MNDA expression in in vitro monocyte-derived macrophages .

As we reported previously , <rna>MNDA mRNA</rna> level in adherent <cell_type>monocytes</cell_type> is elevated by <protein>IFN-alpha</protein> ; in this study , we further assessed <protein>MNDA</protein> expression in in vitro monocyte-derived <cell_type>macrophages</cell_type> .


Three additional agents ( endotoxin , phytohemagglutinin , and phorbol ester ) and other conditions that affect function , cytokine production , differentiation , and/or growth of monocytes were examined for their ability to alter MNDA expression .

Three additional agents ( endotoxin , <protein>phytohemagglutinin</protein> , and phorbol ester ) and other conditions that affect function , <protein>cytokine</protein> production , differentiation , and/or growth of <cell_type>monocytes</cell_type> were examined for their ability to alter <protein>MNDA</protein> expression .


The results varied with the agent , cell type , and stage of differentiation .


Changes in MNDA expression occurred slowly ( hours to days ) , suggesting that MNDA could mediate changes realized over a long period .

Changes in <protein>MNDA</protein> expression occurred slowly ( hours to days ) , suggesting that <protein>MNDA</protein> could mediate changes realized over a long period .


The results also reveal a discordance in certain MNDA positive cells between steady-state levels or changes in levels of protein and mRNA indicating that the regulation of MNDA expression occurs at more than one point .

The results also reveal a discordance in certain <cell_line>MNDA positive cells</cell_line> between steady-state levels or changes in levels of protein and <rna>mRNA</rna> indicating that the regulation of <protein>MNDA</protein> expression occurs at more than one point .


Changes in MNDA expression are consistent with a role in opposing macrophage differentiation and activation of monocytes /macrophages .

Changes in <protein>MNDA</protein> expression are consistent with a role in opposing macrophage differentiation and activation of <cell_type>monocytes</cell_type> <cell_type>/macrophages</cell_type> .


DNA-binding studies of the Epstein-Barr virus nuclear antigen 2 ( EBNA-2 ) : evidence for complex formation by latent membrane protein gene promoter-binding proteins in EBNA-2-positive cell lines .

DNA-binding studies of the <protein>Epstein-Barr virus nuclear antigen 2</protein> ( <protein>EBNA-2</protein> ) : evidence for complex formation by <protein>latent membrane protein gene promoter-binding proteins</protein> in <cell_line>EBNA-2-positive cell lines</cell_line> .


The Epstein-Barr virus ( EBV ) nuclear antigen 2 ( EBNA-2 ) protein is essential for the immortalization of human primary B cells by EBV .

The <protein>Epstein-Barr virus ( EBV ) nuclear antigen 2</protein> ( <protein>EBNA-2</protein> ) protein is essential for the immortalization of <cell_type>human primary B cells</cell_type> by EBV .


EBNA-2 trans-activates cellular and viral genes like CD23 , c-fgr , latent membrane protein 1 ( LMP1 ) and terminal protein 1 ( TP1 ) .

<protein>EBNA-2</protein> trans-activates <dna>cellular and viral genes</dna> like <dna>CD23</dna> , <dna>c-fgr</dna> , <protein>latent membrane protein 1</protein> ( <protein>LMP1</protein> ) and <protein>terminal protein 1</protein> ( <protein>TP1</protein> ) .


Trans-activation of the TP1 promoter and of the BamHI C promoter has already been investigated in detail and appears to be mediated via protein-protein interactions and not by direct binding of EBNA-2 type A ( of EBV type 1 ) to the DNA .

Trans-activation of the <dna>TP1 promoter</dna> and of the <dna>BamHI C promoter</dna> has already been investigated in detail and appears to be mediated via protein-protein interactions and not by direct binding of <protein>EBNA-2 type A</protein> ( of EBV type 1 ) to the DNA .


EBNA-2 is able to trans-activate the expression of the LMP gene in several cell lines .

<protein>EBNA-2</protein> is able to trans-activate the expression of the <dna>LMP gene</dna> in several cell lines .


Various reports have delineated the cis-acting elements of the LMP promoter through which EBNA-2 mediates trans-activation .

Various reports have delineated the <dna>cis-acting elements</dna> of the <dna>LMP promoter</dna> through which <protein>EBNA-2</protein> mediates trans-activation .


To determine whether EBNA-2 also trans-activates the LMP promoter by protein-protein interactions , we performed a series of gel retardation assays and competition experiments with LMP promoter fragments of different sizes .

To determine whether <protein>EBNA-2</protein> also trans-activates the <dna>LMP promoter</dna> by protein-protein interactions , we performed a series of gel retardation assays and competition experiments with <dna>LMP promoter fragments</dna> of different sizes .


We determined that the protein-binding region on the LMP promoter was within a 42 bp fragment encompassing nucleotides -135 to -176 relative to the LMP transcriptional start site .

We determined that the <dna>protein-binding region</dna> on the <dna>LMP promoter</dna> was within a <dna>42 bp fragment</dna> encompassing nucleotides -135 to -176 relative to the <dna>LMP transcriptional start site</dna> .


of the DNA fragments investigated indicated interaction of EBNA-2 with the DNA via protein-protein interactions .

of the DNA fragments investigated indicated interaction of <protein>EBNA-2</protein> with the DNA via protein-protein interactions .


No significant differences between EBNA-2 -positive and EBNA-2 -negative nuclear extracts could be seen in the gel retardation assay under conditions that clearly showed binding of EBNA-2A to the TP1 promoter .

No significant differences between <protein>EBNA-2</protein> -positive and <protein>EBNA-2</protein> -negative nuclear extracts could be seen in the gel retardation assay under conditions that clearly showed binding of <protein>EBNA-2A</protein> to the <dna>TP1 promoter</dna> .


However , analysis of sucrose gradient fractions in the gel retardation assay provided evidence that the LMP promoter-binding proteins form a complex of higher M ( r ) in EBNA-2-positive cell extracts .

However , analysis of sucrose gradient fractions in the gel retardation assay provided evidence that the <protein>LMP promoter-binding proteins</protein> form a complex of higher M ( r ) in <cell_type>EBNA-2-positive cell</cell_type> extracts .


These complexes were destroyed by detergent .


We deduce from these results that EBNA-2-positive cells might indeed contain specific complexes bound to the LMP promoter which are , however , too labile to be detected in a standard gel retardation assay .

We deduce from these results that <cell_line>EBNA-2-positive cells</cell_line> might indeed contain <protein>specific complexes</protein> bound to the <dna>LMP promoter</dna> which are , however , too labile to be detected in a standard gel retardation assay .


Simultaneous activation of Ig and Oct-2 synthesis and reduction of surface MHC class II expression by IL-6 .

Simultaneous activation of <protein>Ig</protein> and <protein>Oct-2</protein> synthesis and reduction of surface <protein>MHC class II</protein> expression by <protein>IL-6</protein> .


Terminal differentiation of B cells to plasma cells in vivo is characterized by secretion of Ig and extinction of MHC class II expression on the cell surface .

Terminal differentiation of <cell_type>B cells</cell_type> to <cell_type>plasma cells</cell_type> in vivo is characterized by secretion of <protein>Ig</protein> and extinction of <protein>MHC class II</protein> expression on the cell surface .


We show that IL-6 signaling leads to marked increases in the synthesis and secretion of Ig in clonal human B cell lines and newly isolated polyclonal B lymphocytes in vitro .

We show that <protein>IL-6</protein> signaling leads to marked increases in the synthesis and secretion of <protein>Ig</protein> in <cell_line>clonal human B cell lines</cell_line> and newly <cell_type>isolated polyclonal B lymphocytes</cell_type> in vitro .


The IL-6-induced cells resemble plasma cells in ultrastructure and in reduced expression of surface MHC class II .

The <cell_line>IL-6-induced cells</cell_line> resemble <cell_type>plasma cells</cell_type> in ultrastructure and in reduced expression of <protein>surface MHC class II</protein> .


Enhanced Ig synthesis is a result of coordinated transcriptional activation of Ig genes without promoter or isotype specificity , and differential accumulation of the mRNA encoding the secreted form of Ig heavy chain .

Enhanced <protein>Ig</protein> synthesis is a result of coordinated transcriptional activation of <dna>Ig genes</dna> without promoter or isotype specificity , and differential accumulation of the <rna>mRNA</rna> encoding the secreted form of <protein>Ig heavy chain</protein> .


It is saturable and subject to negative control when IL-6 stimulation is prolonged .

It is saturable and subject to negative control when <protein>IL-6</protein> stimulation is prolonged .


Coordinate with temporal changes in Ig synthesis , the DNA-binding activity and the synthesis of the B cell-enriched transcription factor Oct-2 are regulated .

Coordinate with temporal changes in <protein>Ig</protein> synthesis , the DNA-binding activity and the synthesis of the <protein>B cell-enriched transcription factor</protein> <protein>Oct-2</protein> are regulated .


Thus , differentiation of B cells with IL-6 in vitro recapitulates the hallmarks of terminal B differentiation in vivo ; Oct-2 may have a role in this process .

Thus , differentiation of <cell_type>B cells</cell_type> with <protein>IL-6</protein> in vitro recapitulates the hallmarks of terminal B differentiation in vivo ; <protein>Oct-2</protein> may have a role in this process .


T-cell functional regions of the human IL-3 proximal promoter .

<dna>T-cell functional regions</dna> of the <dna>human IL-3 proximal promoter</dna> .


The human interleukin-3 ( IL-3 ) gene is expressed almost exclusively in activated T cells .

The <dna>human interleukin-3 ( IL-3 ) gene</dna> is expressed almost exclusively in activated <cell_type>T cells</cell_type> .


Its expression is regulated at both the transcriptional and post-transcriptional level .


We have previously shown that treatment of Jurkat T cells with phytohemaglutinin ( PHA ) and the phorbol ester , PMA , activated transcription initiation from the IL-3 gene .

We have previously shown that treatment of <cell_line>Jurkat T cells</cell_line> with <protein>phytohemaglutinin</protein> ( <protein>PHA</protein> ) and the phorbol ester , PMA , activated transcription initiation from the <dna>IL-3 gene</dna> .


To define the regions of the gene required for transcription activation , we generated a series of reporter constructs containing different regions of the IL-3 gene 5 ' and 3 ' flanking sequences .

To define the regions of the gene required for transcription activation , we generated a series of reporter constructs containing different regions of the <dna>IL-3 gene 5 ' and 3 ' flanking sequences</dna> .


Both positive and negative regulatory elements were identified in the proximal 5 ' flanking region of the IL-3 gene .

Both <dna>positive and negative regulatory elements</dna> were identified in the <dna>proximal 5 ' flanking region</dna> of the <dna>IL-3 gene</dna> .


The promoter region between -173 and -60 contained the strongest activating elements .

The <dna>promoter region</dna> between <dna>-173 and -60</dna> contained the strongest <dna>activating elements</dna> .


The transcription factor AP-1 could bind to this positive activator region of the promoter .

The <protein>transcription factor</protein> <protein>AP-1</protein> could bind to this positive activator region of the promoter .


We also examined the function of the IL-3 CK-1/CK-2 elements that are present in many cytokine genes and found that they acted as a repressor of basal level expression when cloned upstream of a heterologous promoter but were also inducible by PMA /PHA .

We also examined the function of the <dna>IL-3 CK-1/CK-2 elements</dna> that are present in many <dna>cytokine genes</dna> and found that they acted as a repressor of basal level expression when cloned upstream of a <dna>heterologous promoter</dna> but were also inducible by PMA <protein>/PHA</protein> .


Expression of the Runt domain-encoding PEBP2 alpha genes in T cells during thymic development .

Expression of the <dna>Runt domain-encoding PEBP2 alpha genes</dna> in <cell_type>T cells</cell_type> during thymic development .


The PEBP2 alpha A and PEBP2 alpha B genes encode the DNA-binding subunit of a murine transcription factor , PEBP2 , which is implicated as a T-cell-specific transcriptional regulator .

The <dna>PEBP2 alpha A and PEBP2 alpha B genes</dna> encode the <protein>DNA-binding subunit</protein> of a <protein>murine transcription factor</protein> , <protein>PEBP2</protein> , which is implicated as a <protein>T-cell-specific transcriptional regulator</protein> .


These two related genes share the evolutionarily conserved region encoding the Runt domain .

These two related genes share the evolutionarily conserved region encoding the <protein>Runt domain</protein> .


PEBP2 alpha B is the murine counterpart of human AML1 , which is located at the breakpoints of the 8 ; 21 and 3 ; 21 chromosome translocations associated with acute myeloid leukemia .

<protein>PEBP2 alpha B</protein> is the <protein>murine counterpart</protein> of <protein>human AML1</protein> , which is located at the breakpoints of the <dna>8 ; 21 and 3 ; 21 chromosome translocations</dna> associated with acute myeloid leukemia .


Northern ( RNA ) blots of various adult mouse tissues revealed that the levels of expression of both genes were most prominent in the thymus .


Furthermore , transcripts of PEBP2 alpha A and mouse AML1/PEBP2 alpha B were detected in T lymphocytes in the thymuses from day 16 embryos and newborns , as well as 4-week-old adult mice , by in situ hybridization .

Furthermore , transcripts of <protein>PEBP2 alpha A</protein> and <protein>mouse AML1/PEBP2 alpha B</protein> were detected in <cell_type>T lymphocytes</cell_type> in the thymuses from day 16 embryos and newborns , as well as 4-week-old adult mice , by in situ hybridization .


The expression of the genes persisted in peripheral lymph nodes of adult mice .


The transcripts were detected in all the CD4- CD8- , CD4+ CD8+ , CD4+ CD8- , and CD4- CD8+ cell populations .

The transcripts were detected in all the <cell_type>CD4- CD8- , CD4+ CD8+ , CD4+ CD8- , and CD4- CD8+ cell populations</cell_type> .


The results indicated that both genes are expressed in T cells throughout their development , supporting the notion that PEBP2 is a T-cell-specific transcription factor .

The results indicated that both genes are expressed in <cell_type>T cells</cell_type> throughout their development , supporting the notion that <protein>PEBP2</protein> is a <protein>T-cell-specific transcription factor</protein> .


Transcripts of mouse AML1/PEBP2 alpha B were also detected in day 12 fetal hematopoietic liver and in the bone marrow cells of newborn mice .

Transcripts of <protein>mouse AML1/PEBP2 alpha B</protein> were also detected in day 12 fetal hematopoietic liver and in the <cell_type>bone marrow cells</cell_type> of newborn mice .


The implication of mouse AML1/PEBP2 alpha B expression in hematopoietic cells other than those of T-cell lineage is discussed in relation to myeloid leukemogenesis .

The implication of mouse <protein>AML1/PEBP2 alpha B</protein> expression in <cell_type>hematopoietic cells</cell_type> other than those of <cell_type>T-cell lineage</cell_type> is discussed in relation to myeloid leukemogenesis .


Effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cells .

Effects of glucocorticoids on transcription factor activation in <cell_type>human peripheral blood mononuclear cells</cell_type> .


Glucocorticoids have an inhibitory effect on inflammatory and immune responses , and this may be through the modulation of transcription factor binding to DNA .

Glucocorticoids have an inhibitory effect on inflammatory and immune responses , and this may be through the modulation of <protein>transcription factor</protein> binding to DNA .


The interaction of the transcription factors , activator protein-1 ( AP-1 ) , nuclear factor kappa B ( NF kappa B ) , and cAMP-responsive element binding protein ( CREB ) with DNA and glucocorticoid receptors ( GR ) was analyzed in human peripheral blood mononuclear cells by gel mobility shift assays .

The interaction of the <protein>transcription factors</protein> , <protein>activator protein-1</protein> ( <protein>AP-1</protein> ) , <protein>nuclear factor kappa B</protein> ( <protein>NF kappa B</protein> ) , and <protein>cAMP-responsive element binding protein</protein> ( <protein>CREB</protein> ) with DNA and <protein>glucocorticoid receptors</protein> ( <protein>GR</protein> ) was analyzed in <cell_type>human peripheral blood mononuclear cells</cell_type> by gel mobility shift assays .


TNF-alpha , IL-1 beta and phorbol myristate acetate ( PMA ) treatment increased AP-1 and NF kappa B DNA binding by up to 200 % but decreased CREB binding ( 38 % ) over a 60-min time course .

TNF-alpha , IL-1 beta and phorbol myristate acetate ( PMA ) treatment increased <protein>AP-1</protein> and NF kappa B DNA binding by up to 200 % but decreased <protein>CREB</protein> binding ( 38 % ) over a 60-min time course .


Dexamethasone produced a rapid and sustained increase in glucocorticoid response element binding and a concomitant 40-50 % decrease in AP-1 , NF kappa B , and CREB DNA binding that was blocked by combined dexamethasone and cytokine or PMA treatment .

Dexamethasone produced a rapid and sustained increase in <dna>glucocorticoid response element</dna> binding and a concomitant 40-50 % decrease in AP-1 , NF kappa B , and CREB DNA binding that was blocked by combined dexamethasone and <protein>cytokine</protein> or PMA treatment .


These latter effects were due to increases in the nuclear localization of GR , not to reduced amounts of the other transcription factors .

These latter effects were due to increases in the nuclear localization of <protein>GR</protein> , not to reduced amounts of the other <protein>transcription factors</protein> .


This suggests that in these cells GR within the nucleus interacts with cytokine-stimulated transcription factors by the process of cross coupling .

This suggests that in these cells <protein>GR</protein> within the nucleus interacts with <protein>cytokine-stimulated transcription factors</protein> by the process of cross coupling .


This may be an important molecular site of steroid action .


Differential induction of the NF-AT complex during restimulation and the induction of T-cell anergy .

Differential induction of the <protein>NF-AT complex</protein> during restimulation and the induction of T-cell anergy .


Stimulation of human CD4+ T-cell clones through the T-cell receptor ( TcR ) by high doses of specific peptide results in the induction of a long-lived state of nonresponsiveness that has been called anergy .

Stimulation of <cell_line>human CD4+ T-cell clones</cell_line> through the <protein>T-cell receptor</protein> ( <protein>TcR</protein> ) by high doses of specific peptide results in the induction of a long-lived state of nonresponsiveness that has been called anergy .


During the induction of anergy , T cells are phenotypically similar to cells responding to an immunogenic stimulus .

During the induction of anergy , <cell_type>T cells</cell_type> are phenotypically similar to cells responding to an immunogenic stimulus .


The amount of TcR at the cell surface is downmodulated , whereas the CD2 and CD25 receptors are increased .

The amount of <protein>TcR</protein> at the cell surface is downmodulated , whereas the <protein>CD2 and CD25 receptors</protein> are increased .


When restimulated , however , anergic T cells fail to up-regulate transcription of the IL-2 gene and in consequence do not produce IL-2 .

When restimulated , however , <cell_type>anergic T cells</cell_type> fail to up-regulate transcription of the <dna>IL-2 gene</dna> and in consequence do not produce <protein>IL-2</protein> .


In this study , we have compared the ability of various transcription factors to bind to their appropriate site on DNA .

In this study , we have compared the ability of various <protein>transcription factors</protein> to bind to their appropriate site on DNA .


Factors were isolated from the nuclei of T cells that were in the induction phase of anergy or were undergoing activation .

Factors were isolated from the nuclei of <cell_type>T cells</cell_type> that were in the induction phase of anergy or were undergoing activation .


The pattern of binding activity in restimulated T cells is consistent with the pattern that has previously been shown to regulate T-cell-specific expression of the IL-2 and the beta chain of the TcR genes .

The pattern of binding activity in restimulated <cell_type>T cells</cell_type> is consistent with the pattern that has previously been shown to regulate T-cell-specific expression of the <protein>IL-2</protein> and the beta chain of the <dna>TcR genes</dna> .


The measured binding to a TCF-1 site is the same in the nuclei of resting , activated , and anergized cells .

The measured binding to a <dna>TCF-1 site</dna> is the same in the nuclei of <cell_type>resting , activated , and anergized cells</cell_type> .


The inducible factors NK-kappa B , beta E2 , CD28RC , and AP-1 are not expressed in resting cells and are twofold lower in anergized as compared with activated cells .

The <protein>inducible factors</protein> <protein>NK-kappa B</protein> , <protein>beta E2</protein> , <protein>CD28RC</protein> , and <protein>AP-1</protein> are not expressed in <cell_type>resting cells</cell_type> and are twofold lower in anergized as compared with activated cells .


In contrast , anergic T cells express approximately eightfold lower amounts of NF-AT , a member of the class of inducible factors that regulates IL-2 gene transcription .

In contrast , <cell_type>anergic T cells</cell_type> express approximately eightfold lower amounts of <protein>NF-AT</protein> , a member of the class of <protein>inducible factors</protein> that regulates <dna>IL-2 gene</dna> transcription .


( ABSTRACT TRUNCATED AT 250 WORDS )


The number of glucocorticoid receptors in peripheral human lymphocytes is elevated by a zinc containing trace element preparation .

The number of <protein>glucocorticoid receptors</protein> in <cell_type>peripheral human lymphocytes</cell_type> is elevated by a zinc containing trace element preparation .


A trace element preparation ( Beres Drops Plus , BDP ) elevates the number of glucocorticoid receptors ( gcR ) in peripheral lymphocytes isolated both from healthy blood donors and rheumatoid arthritis patients .

A trace element preparation ( Beres Drops Plus , BDP ) elevates the number of <protein>glucocorticoid receptors</protein> ( <protein>gcR</protein> ) in <cell_type>peripheral lymphocytes</cell_type> isolated both from healthy blood donors and rheumatoid arthritis patients .


This enhancement by BDP was found either for constitutive expression of gcRs or in experiments when the lymphocytes were stimulated by interleukin ( IL ) -6 .

This enhancement by BDP was found either for constitutive expression of <protein>gcRs</protein> or in experiments when the <cell_type>lymphocytes</cell_type> were stimulated by <protein>interleukin ( IL ) -6</protein> .


There was no significant effect of BDP on IL-1 and tumour necrosis factor alpha ( TNF alpha ) -induced changes of gcRs .

There was no significant effect of BDP on <protein>IL-1</protein> and <protein>tumour necrosis factor alpha</protein> ( <protein>TNF alpha</protein> ) -induced changes of <protein>gcRs</protein> .


The effect of BDP was greatly dependent on the presence of Zn++ ions in the preparation , since the augmenting effect was abolished if BDP did not contain zinc .


The DNA and steroid binding domains of the glucocorticoid receptor are not altered in mononuclear cells of treated CLL patients .

The DNA and <protein>steroid binding domains</protein> of the <protein>glucocorticoid receptor</protein> are not altered in <cell_type>mononuclear cells</cell_type> of treated CLL patients .


The aim of this study was to investigate whether mutations in the glucocorticoid receptor could account for the increasing unresponsiveness of patients with chronic lymphatic leukemia ( CLL ) to combination chemotherapy .

The aim of this study was to investigate whether mutations in the <protein>glucocorticoid receptor</protein> could account for the increasing unresponsiveness of patients with chronic lymphatic leukemia ( CLL ) to combination chemotherapy .


The receptor was tested immunocytochemically , in steroid binding assays , and by a mutation screening ( denaturing gradient gel electrophoresis ) of the receptor-cDNA .

The receptor was tested immunocytochemically , in steroid binding assays , and by a mutation screening ( denaturing gradient gel electrophoresis ) of the <protein>receptor-cDNA</protein> .


The receptor concentration , as measured by staining and steroid binding test , varied considerably but showed no clear correlation to clinical response .


Using a highly sensitive mutation screening assay of the DNA- and the steroid-binding region , none of the treated patients revealed any mutation , suggesting that the glucocorticoid receptor in the CLL patients tested is not altered in these domains .

Using a highly sensitive mutation screening assay of the <protein>DNA- and the steroid-binding region</protein> , none of the treated patients revealed any mutation , suggesting that the <protein>glucocorticoid receptor</protein> in the CLL patients tested is not altered in these domains .


In one individual who had not been treated before analysis a silent mutation was found in one receptor allele .


The results suggest that mechanisms other than altered ligand or DNA binding of the receptor may be responsible for the lack of response to chemotherapy .


This conclusion is discussed in relation to the mechanism of corticoid resistance in mouse and human lymphoma cells in culture .

This conclusion is discussed in relation to the mechanism of corticoid resistance in <cell_line>mouse and human lymphoma cells</cell_line> in culture .


An AP1 binding site upstream of the kappa immunoglobulin intron enhancer binds inducible factors and contributes to expression .

An <dna>AP1 binding site</dna> upstream of the <dna>kappa immunoglobulin intron enhancer</dna> binds <protein>inducible factors</protein> and contributes to expression .


Expression of the kappa immunoglobulin light chain gene requires developmental- and tissue-specific regulation by trans-acting factors which interact with two distinct enhancer elements .

Expression of the kappa immunoglobulin light chain gene requires developmental- and tissue-specific regulation by <protein>trans-acting factors</protein> which interact with two distinct <dna>enhancer elements</dna> .


A new protein-DNA interaction has been identified upstream of the intron enhancer , within the matrix-associated region of the J-C intron .

A new protein-DNA interaction has been identified upstream of the <dna>intron enhancer</dna> , within the <dna>matrix-associated region</dna> of the <dna>J-C intron</dna> .


The binding activity is greatly inducible in pre-B cells by bacterial lipopolysaccharide and interleukin-1 but specific complexes are found at all stages of B cell development tested .

The binding activity is greatly inducible in <cell_type>pre-B cells</cell_type> by bacterial lipopolysaccharide and <protein>interleukin-1</protein> but specific complexes are found at all stages of B cell development tested .


The footprinted binding site is homologous to the consensus AP1 motif .

The <dna>footprinted binding site</dna> is homologous to the <dna>consensus AP1 motif</dna> .


The protein components of this complex are specifically competed by an AP1 consensus motif and were shown by supershift to include c-Jun and c-Fos , suggesting that this binding site is an AP1 motif and that the Jun and Fos families of transcription factors play a role in the regulation of the kappa light chain gene .

The protein components of this complex are specifically competed by an <dna>AP1 consensus motif</dna> and were shown by supershift to include <protein>c-Jun</protein> and <protein>c-Fos</protein> , suggesting that this <dna>binding site</dna> is an <dna>AP1 motif</dna> and that the <protein>Jun and Fos families</protein> of <protein>transcription factors</protein> play a role in the regulation of the <dna>kappa light chain gene</dna> .


Mutation of the AP1 motif in the context of the intron enhancer was shown to decrease enhancer-mediated activation of the promoter in both pre-B cells induced with LPS and constitutive expression in mature B cells .

Mutation of the <dna>AP1 motif</dna> in the context of the <dna>intron enhancer</dna> was shown to decrease enhancer-mediated activation of the promoter in both <cell_type>pre-B cells</cell_type> induced with LPS and constitutive expression in <cell_type>mature B cells</cell_type> .


Distinct DNase-I hypersensitive sites are associated with TAL-1 transcription in erythroid and T-cell lines .

Distinct <dna>DNase-I hypersensitive sites</dna> are associated with <protein>TAL-1</protein> transcription in <cell_line>erythroid and T-cell lines</cell_line> .


The tal-1 gene , frequently activated in human T-cell acute lymphoblastic leukemia ( T-ALL ) , is expressed in the erythroid , megakaryocytic , and mast cell lineages during normal hematopoiesis .

The <dna>tal-1 gene</dna> , frequently activated in human T-cell acute lymphoblastic leukemia ( T-ALL ) , is expressed in the <cell_type>erythroid , megakaryocytic , and mast cell lineages</cell_type> during normal hematopoiesis .


To gain further insight into the molecular mechanisms that control tal-1 expression , we investigated tal-1 chromatin structure in erythroid/megakaryocytic cell lines and in T-cell lines either with or without tal-1 rearrangements .

To gain further insight into the molecular mechanisms that control <dna>tal-1</dna> expression , we investigated <dna>tal-1</dna> chromatin structure in <cell_line>erythroid/megakaryocytic cell lines</cell_line> and in <cell_line>T-cell lines</cell_line> either with or without <dna>tal-1 rearrangements</dna> .


Tal-1 transcription was shown to be monoallelic in Jurkat , a T-cell line that expresses tal-1 in the absence of apparent genomic alteration of the locus .

Tal-1 transcription was shown to be monoallelic in <cell_line>Jurkat</cell_line> , a T-cell line that expresses <dna>tal-1</dna> in the absence of apparent genomic alteration of the locus .


Methylation studies indicated that the tal-15 ' GC-rich region behaves like a CpG island , hypomethylated in normal cells , and methylated de novo on transcriptionally inactive alleles in established cell lines .

Methylation studies indicated that the <dna>tal-15 ' GC-rich region</dna> behaves like a <dna>CpG island</dna> , hypomethylated in <cell_type>normal cells</cell_type> , and methylated de novo on <dna>transcriptionally inactive alleles</dna> in <cell_line>established cell lines</cell_line> .


Five major DNase-I hypersensitive sites ( HS ) were mapped in the tal-1 locus .

Five major <dna>DNase-I hypersensitive sites</dna> ( <dna>HS</dna> ) were mapped in the <dna>tal-1</dna> locus .


HS I , IV , and V were exclusively observed in the erythroid/megakaryocytic cell lines that express tal-1 from the promoters 1a and 1b .

<dna>HS I , IV , and V</dna> were exclusively observed in the <cell_line>erythroid/megakaryocytic cell lines</cell_line> that express <dna>tal-1</dna> from the <dna>promoters 1a and 1b</dna> .


HS II was weak in hematopoietic cell lines , absent in Hela , and greatly enhanced in Jurkat , suggesting that this region might be implicated in the cis-activation of tal-1 promoter 1b in this cell line .

<dna>HS II</dna> was weak in <cell_line>hematopoietic cell lines</cell_line> , absent in <cell_line>Hela</cell_line> , and greatly enhanced in <cell_line>Jurkat</cell_line> , suggesting that this region might be implicated in the cis-activation of <dna>tal-1 promoter 1b</dna> in this cell line .


HS III was weak in HEL and Jurkat , and greatly enhanced in DU528 , a T-cell line that bears a t ( 1 ; 14 ) and initiates tal-1 transcription within exon 4 .

<dna>HS III</dna> was weak in <cell_line>HEL</cell_line> and <cell_line>Jurkat</cell_line> , and greatly enhanced in <cell_line>DU528</cell_line> , a <cell_line>T-cell line</cell_line> that bears <dna>a t ( 1 ; 14 )</dna> and initiates <dna>tal-1</dna> transcription within <dna>exon 4</dna> .


These results suggest that distinct regulatory elements are associated with the use of the different tal-1 promoters .

These results suggest that distinct <dna>regulatory elements</dna> are associated with the use of the different <dna>tal-1 promoters</dna> .


Erythropoietin -dependent induction of hemoglobin synthesis in a cytokine-dependent cell line M-TAT .

<protein>Erythropoietin</protein> -dependent induction of <protein>hemoglobin</protein> synthesis in a <cell_line>cytokine-dependent cell line</cell_line> <cell_line>M-TAT</cell_line> .


M-TAT is a cytokine-dependent cell line with the potential to differentiate along the erythroid and megakaryocytic lineages .

<cell_line>M-TAT</cell_line> is a <cell_line>cytokine-dependent cell line</cell_line> with the potential to differentiate along the <cell_type>erythroid and megakaryocytic lineages</cell_type> .


We cultured M-TAT cells long term ( > 1 year ) in the continuous presence of erythropoietin ( EPO ) , granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , or stem cell factor ( SCF ) .

We cultured <cell_line>M-TAT cells</cell_line> long term ( > 1 year ) in the continuous presence of <protein>erythropoietin</protein> ( <protein>EPO</protein> ) , <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) , or <protein>stem cell factor</protein> ( <protein>SCF</protein> ) .


These long term cultures are referred to as M-TAT/EPO , M-TAT/GM-CSF , and M-TAT/SCF cells , respectively .

These long term cultures are referred to as <cell_line>M-TAT/EPO , M-TAT/GM-CSF , and M-TAT/SCF cells</cell_line> , respectively .


Hemoglobin concentration and gamma-globin and erythroid delta-aminolevulinate synthase mRNA levels were significantly higher in M-TAT/EPO cells than in M-TAT/GM-CSF cells .

<protein>Hemoglobin</protein> concentration and <protein>gamma-globin</protein> and <rna>erythroid delta-aminolevulinate synthase mRNA</rna> levels were significantly higher in <cell_line>M-TAT/EPO cells</cell_line> than in <cell_line>M-TAT/GM-CSF cells</cell_line> .


When the supplemented cytokine was switched from GM-CSF to EPO , hemoglobin synthesis in M-TAT/GM-CSF cells increased rapidly ( within 5 h ) , and the level of GATA-1 mRNA increased .

When the supplemented <protein>cytokine</protein> was switched from <protein>GM-CSF</protein> to <protein>EPO</protein> , <protein>hemoglobin</protein> synthesis in <cell_line>M-TAT/GM-CSF cells</cell_line> increased rapidly ( within 5 h ) , and the level of <rna>GATA-1 mRNA</rna> increased .


In contrast , the addition of GM-CSF to the M-TAT/EPO cell culture decreased the amount of hemoglobin , even in the presence of EPO , indicating that the EPO signal for erythroid differentiation is suppressed by GM-CSF .

In contrast , the addition of <protein>GM-CSF</protein> to the <cell_line>M-TAT/EPO cell culture</cell_line> decreased the amount of hemoglobin , even in the presence of <protein>EPO</protein> , indicating that the <protein>EPO</protein> signal for erythroid differentiation is suppressed by <protein>GM-CSF</protein> .


Thus , erythroid development of M-TAT cells is promoted by EPO and suppressed by GM-CSF .

Thus , erythroid development of <cell_line>M-TAT cells</cell_line> is promoted by <protein>EPO</protein> and suppressed by <protein>GM-CSF</protein> .


These results support the hypothesis that EPO actively influences the programming of gene expression required for erythroid progenitor cell differentiation .

These results support the hypothesis that <protein>EPO</protein> actively influences the programming of gene expression required for <cell_type>erythroid progenitor cell</cell_type> differentiation .


The role of cellular transcription factor E2F in the regulation of cdc2 mRNA expression and cell cycle control of human hematopoietic cells .

The role of <protein>cellular transcription factor E2F</protein> in the regulation of <rna>cdc2 mRNA</rna> expression and cell cycle control of human <cell_type>hematopoietic cells</cell_type> .


cdc2 mRNA transcripts were detected in immature bone marrow cells and became undetectable along with differentiation .

<rna>cdc2 mRNA transcripts</rna> were detected in <cell_type>immature bone marrow cells</cell_type> and became undetectable along with differentiation .


Peripheral blood resting cells did not express cdc2 mRNA , but it was induced in T-lymphocytes when the cells reentered the cell cycle in response to specific mitogens .

<cell_type>Peripheral blood resting cells</cell_type> did not express <rna>cdc2 mRNA</rna> , but it was induced in <cell_type>T-lymphocytes</cell_type> when the cells reentered the cell cycle in response to specific mitogens .


In contrast , cdc2 mRNA could not be induced in granulocytes and monocytes even after the culture with the appropriate stimulants .

In contrast , <rna>cdc2 mRNA</rna> could not be induced in <cell_type>granulocytes</cell_type> and <cell_type>monocytes</cell_type> even after the culture with the appropriate stimulants .


In order to investigate the mechanism of the regulation of cdc2 mRNA expression in hematopoietic cells , we isolated the 5'-flanking sequence of the cdc2 gene and found the putative E2F binding site at the position of nucleotides -124 to -117 .

In order to investigate the mechanism of the regulation of <rna>cdc2 mRNA</rna> expression in <cell_type>hematopoietic cells</cell_type> , we isolated the <dna>5'-flanking sequence</dna> of the <dna>cdc2 gene</dna> and found the putative E2F <dna>binding site</dna> at the position of <dna>nucleotides -124 to -117</dna> .


The binding of E2F at this region was detected by a gel-retardation assay and DNaseI footprinting in phytohemagglutinin-stimulated T-lymphocytes , which was coincident with the expression of cdc2 mRNA .

The binding of <protein>E2F</protein> at this region was detected by a gel-retardation assay and <protein>DNaseI</protein> footprinting in <cell_line>phytohemagglutinin-stimulated T-lymphocytes</cell_line> , which was coincident with the expression of <rna>cdc2 mRNA</rna> .


E2F binding was not observed in both granulocytes and monocytes .

<protein>E2F</protein> binding was not observed in both <cell_type>granulocytes</cell_type> and <cell_type>monocytes</cell_type> .


Transient chloramphenicol acetyltransferase assay revealed that the region containing E2F binding site had a strong promoter activity , and introduction of the mutation at the E2F binding site resulted in a significant loss of the activity .

Transient <protein>chloramphenicol acetyltransferase</protein> assay revealed that the region containing <dna>E2F binding site</dna> had a strong promoter activity , and introduction of the mutation at the <dna>E2F binding site</dna> resulted in a significant loss of the activity .


E2F-1 and DP-1 mRNAs were not detectable in granulocytes , monocytes and resting T-lymphocytes but were induced after the mitogenic stimulation of T-lymphocytes .

<rna>E2F-1 and DP-1 mRNAs</rna> were not detectable in <cell_type>granulocytes</cell_type> , <cell_type>monocytes</cell_type> and <cell_type>resting T-lymphocytes</cell_type> but were induced after the mitogenic stimulation of <cell_type>T-lymphocytes</cell_type> .


The induction of E2F activity preceded the appearance of cdc2 mRNA , which is consistent with the role of E2F in the regulation of cdc2 mRNA expression .

The induction of <protein>E2F</protein> activity preceded the appearance of <rna>cdc2 mRNA</rna> , which is consistent with the role of <protein>E2F</protein> in the regulation of <cell_type>cdc2 mRNA expression</cell_type> .


These results suggest that cdc2 mRNA expression is related to the cell cycling of normal human hematopoietic cells and that E2F plays some roles in the regulation of its expression .

These results suggest that <rna>cdc2 mRNA</rna> expression is related to the cell cycling of <cell_type>normal human hematopoietic cells</cell_type> and that <protein>E2F</protein> plays some roles in the regulation of its expression .


Association of alterations in NF-kappa B moieties with HIV type 1 proviral latency in certain monocytic cells .

Association of alterations in <protein>NF-kappa B moieties</protein> with HIV type 1 proviral latency in certain <cell_type>monocytic cells</cell_type> .


Human immunodeficiency virus type 1 ( HIV-1 ) replication is controlled by a complex array of virally encoded and cellular proteins .

Human immunodeficiency virus type 1 ( HIV-1 ) replication is controlled by a complex array of <protein>virally encoded and cellular proteins</protein> .


A wide spectrum of levels of HIV-1 expression have been demonstrated in various cells , both in cell culture and in vivo .


Molecular mechanisms leading to restricted HIV-1 replication may differ between certain cell types .


It is now demonstrated that HIV-1 proviral latency in the monocytic cell line U1 , in which only extremely low levels of HIV-1 expression are detected in the baseline unstimulated state , is associated with alterations in nuclear factor-kappa B ( NF-kappa B ) moieties demonstrated in these cells by electrophoretic mobility shift assays ( EMSAs ) and in situ UV cross-linking studies .

It is now demonstrated that HIV-1 proviral latency in the <cell_line>monocytic cell line U1</cell_line> , in which only extremely low levels of HIV-1 expression are detected in the baseline unstimulated state , is associated with alterations in nuclear <protein>factor-kappa B ( NF-kappa B ) moieties</protein> demonstrated in these cells by electrophoretic mobility shift assays ( EMSAs ) and in situ UV cross-linking studies .


A predominance of p50 NF-kappa B moieties and possibly p50 homodimers or closely related species , rather than the p50-p56 heterodimer of NF-kappa B that is the predominant NF-kappa B species in most T lymphocytic and monocytic cells , is demonstrated in the nuclei of U1 cells .

A predominance of <protein>p50 NF-kappa B moieties</protein> and possibly <protein>p50 homodimers</protein> or closely related species , rather than the <protein>p50-p56 heterodimer</protein> of <protein>NF-kappa B</protein> that is the predominant <protein>NF-kappa B</protein> species in most <cell_type>T lymphocytic and monocytic cells</cell_type> , is demonstrated in the nuclei of <cell_line>U1 cells</cell_line> .


This pattern of NF-kappa B-related moieties differs from the latently infected T lymphocytic cell line ACH-2 , and from the U937 monocytic line , the parental cell line of the U1 cellular clone .

This pattern of <protein>NF-kappa B-related moieties</protein> differs from the <cell_line>latently infected T lymphocytic cell line ACH-2</cell_line> , and from the <cell_line>U937 monocytic line</cell_line> , the <cell_line>parental cell line</cell_line> of the <cell_line>U1 cellular clone</cell_line> .


As such , these data suggest that different proximal mechanisms may lead to restricted HIV-1 replication in various cell types .


[ Regulation of transcription of the interleukin-2 gene in B-lymphocytes ]

[ Regulation of transcription of the <dna>interleukin-2 gene</dna> in <cell_type>B-lymphocytes</cell_type> ]


Since most B cell clones immortalized with EBV virus can be induced to produce interleukin-2 , a typical T cell cytokine , we studied the role of different elements of the IL-2 promoter in such clones by transfection .

Since most <cell_line>B cell clones</cell_line> immortalized with EBV virus can be induced to produce <protein>interleukin-2</protein> , a typical <protein>T cell cytokine</protein> , we studied the role of different elements of the <dna>IL-2 promoter</dna> in such clones by transfection .


It was found , in particular , that the element TCEd , which binds the transcription factor NF-kB , is very active in all three B clones tested .

It was found , in particular , that the element <dna>TCEd</dna> , which binds the <protein>transcription factor</protein> <protein>NF-kB</protein> , is very active in all three <cell_line>B clones</cell_line> tested .


This element has no activity in T cells of the Jurkat line .

This element has no activity in <cell_type>T cells</cell_type> of the <cell_line>Jurkat line</cell_line> .


The NFATd element , which binds the transcription factor NFAT-1 and is very active in T cells , is only weakly active in one B clone and not at all in another .

The <dna>NFATd element</dna> , which binds the <protein>transcription factor</protein> <protein>NFAT-1</protein> and is very active in <cell_type>T cells</cell_type> , is only weakly active in one <cell_line>B clone</cell_line> and not at all in another .


Different elements thus contribute to IL-2 promoter activity in different cells .

Different elements thus contribute to <dna>IL-2 promoter</dna> activity in different cells .


Regulation of I kappa B alpha and p105 in monocytes and macrophages persistently infected with human immunodeficiency virus .

Regulation of <protein>I kappa B alpha</protein> and <protein>p105</protein> in <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> persistently infected with human immunodeficiency virus .


The mechanisms regulating human immunodeficiency virus ( HIV ) persistence in human monocytes /macrophages are partially understood .

The mechanisms regulating human immunodeficiency virus ( HIV ) persistence in human <cell_type>monocytes</cell_type> <cell_type>/macrophages</cell_type> are partially understood .


Persistent HIV infection of U937 monocytic cells results in NF-kappa B activation .

Persistent HIV infection of <cell_line>U937 monocytic cells</cell_line> results in <protein>NF-kappa B</protein> activation .


Whether virus-induced NF-kappa B activation is a mechanism that favors continuous viral replication in macrophages remains unknown .

Whether virus-induced <protein>NF-kappa B</protein> activation is a mechanism that favors continuous viral replication in <cell_type>macrophages</cell_type> remains unknown .


To further delineate the molecular mechanisms involved in the activation of NF-kappa B in HIV-infected monocytes and macrophages , we have focused on the regulation of the I kappa B molecules .

To further delineate the molecular mechanisms involved in the activation of <protein>NF-kappa B</protein> in HIV-infected <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> , we have focused on the regulation of the I kappa B molecules .


First , we show that persistent HIV infection results in the activation of NF-kappa B not only in monocytic cells but also in macrophages .

First , we show that persistent HIV infection results in the activation of NF-kappa B not only in monocytic cells but also in <cell_type>macrophages</cell_type> .


In HIV-infected cells , I kappa B alpha protein levels are decreased secondary to enhanced protein degradation .

In HIV-infected cells , <protein>I kappa B alpha</protein> protein levels are decreased secondary to enhanced protein degradation .


This parallels the increased I kappa B alpha synthesis secondary to increased I kappa B alpha gene transcription , i.e. , increased RNA and transcriptional activity of its promoter-enhancer .

This parallels the increased <protein>I kappa B alpha</protein> synthesis secondary to increased <protein>I kappa B alpha</protein> gene transcription , i.e. , increased RNA and transcriptional activity of its promoter-enhancer .


Another protein with I kappa B function , p105 , is also modified in HIV-infected cells : p105 and p50 steady-state protein levels are increased as a result of increased synthesis and proteolytic processing of p105 .

Another protein with I kappa B function , <protein>p105</protein> , is also modified in HIV-infected cells : <protein>p105</protein> and <protein>p50</protein> steady-state protein levels are increased as a result of increased synthesis and proteolytic processing of <protein>p105</protein> .


Transcriptional activity of p105 is also increased in infected cells and is also mediated by NF-kappa B through a specific kappa B motif .

Transcriptional activity of <protein>p105</protein> is also increased in <cell_type>infected cells</cell_type> and is also mediated by <protein>NF-kappa B</protein> through a specific <dna>kappa B motif</dna> .


These results demonstrate the existence of a triple autoregulatory loop in monocytes and macrophages involving HIV , p105 and p50 , and MAD3 , with the end result of persistent NF-kappa B activation and viral persistence .

These results demonstrate the existence of a triple autoregulatory loop in <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> involving HIV , <protein>p105</protein> and <protein>p50</protein> , and <protein>MAD3</protein> , with the end result of persistent NF-kappa B activation and viral persistence .


Furthermore , persistent HIV infection of monocytes and macrophages provides a useful model with which to study concomitant modifications of different I kappa B molecules .

Furthermore , persistent HIV infection of <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> provides a useful model with which to study concomitant modifications of different <protein>I kappa B molecules</protein> .


Glucocorticoid-induced apoptosis of human leukemic cells is caused by the repressive function of the glucocorticoid receptor .

Glucocorticoid-induced apoptosis of <cell_type>human leukemic cells</cell_type> is caused by the repressive function of the <protein>glucocorticoid receptor</protein> .


Induction of apoptosis in lymphocytes , which may account for the therapeutic effects of glucocorticoids in various diseases including leukemia , depends on the glucocorticoid receptor .

Induction of apoptosis in <cell_type>lymphocytes</cell_type> , which may account for the therapeutic effects of glucocorticoids in various diseases including leukemia , depends on the <protein>glucocorticoid receptor</protein> .


However , the events leading from the activated receptor to cell lysis are not understood .


A prevailing hypothesis postulates induction of so-called ' lysis genes ' by the activated receptor .

A prevailing hypothesis postulates induction of so-called ' <dna>lysis genes</dna> ' by the <protein>activated receptor</protein> .


In this study , we show that an activation-deficient glucocorticoid receptor mutant is as effective as the wild-type receptor in repression of AP-1 activity , inhibition of interleukin-2 production , inhibition of c-myc expression and induction of apoptosis .

In this study , we show that an <protein>activation-deficient glucocorticoid receptor mutant</protein> is as effective as the <protein>wild-type receptor</protein> in repression of <protein>AP-1</protein> activity , inhibition of <protein>interleukin-2</protein> production , inhibition of <dna>c-myc</dna> expression and induction of apoptosis .


Furthermore , we show that retinoic acid can also induce apoptosis in these cells through the retinoic acid receptor , whose repressive functions but not target site specificity , are similar to those of the glucocorticoid receptor .

Furthermore , we show that retinoic acid can also induce apoptosis in these cells through the <protein>retinoic acid receptor</protein> , whose repressive functions but not target site specificity , are similar to those of the <protein>glucocorticoid receptor</protein> .


Therefore , the primary effect of the receptor in glucocorticoid-mediated apoptosis correlates with transcriptional repression rather than activation and could be mediated by interference with other transcription factors required for cell survival .

Therefore , the primary effect of the receptor in glucocorticoid-mediated apoptosis correlates with transcriptional repression rather than activation and could be mediated by interference with other <protein>transcription factors</protein> required for cell survival .


HIV type 1 protease activation of NF-kappa B within T lymphoid cells .

HIV type 1 <protein>protease</protein> activation of <protein>NF-kappa B</protein> within <cell_type>T lymphoid cells</cell_type> .


NF-kappa B is a nuclear protein of the rel oncogene family capable of enhancing transcription of several cellular genes , including IL-2 and the IL-2 receptor , and viral genes transcribed from the HIV-1 LTR .

<protein>NF-kappa B</protein> is a <protein>nuclear protein</protein> of the <protein>rel oncogene family</protein> capable of enhancing transcription of <dna>several cellular genes</dna> , including <protein>IL-2</protein> and the <protein>IL-2 receptor</protein> , and <dna>viral genes</dna> transcribed from the <dna>HIV-1 LTR</dna> .


It has been reported that HIV-1 protease may cleave the NF-kappa B precursor to its active form in vitro .

It has been reported that <protein>HIV-1 protease</protein> may cleave the <protein>NF-kappa B</protein> precursor to its active form in vitro .


In this study the effects of HIV protease on NF-kappa B precursor activation were examined in Jurkat T cells by introducing a protease expression vector into the cells .

In this study the effects of HIV protease on <protein>NF-kappa B</protein> precursor activation were examined in Jurkat <cell_type>T cells</cell_type> by introducing a <dna>protease expression vector</dna> into the cells .


Increased NF-kappa B activity was observed and this increased activity was blocked by a specific inhibitor of the viral protease .

Increased <protein>NF-kappa B</protein> activity was observed and this increased activity was blocked by a specific inhibitor of the <protein>viral protease</protein> .


Viral transcription , as measured using LTR -CAT assays , was only slightly enhanced in the HIV-protease expressing cells , while secretion of IL-2 and expression of the IL-2 receptor were not affected .

Viral transcription , as measured using <dna>LTR</dna> <protein>-CAT</protein> assays , was only slightly enhanced in the <cell_type>HIV-protease expressing cells</cell_type> , while secretion of <protein>IL-2</protein> and expression of the <protein>IL-2</protein> receptor were not affected .


The limited activation of NF-kappa B by HIV protease appears unlikely to have a significant effect on virus expression or T cell function .

The limited activation of <protein>NF-kappa B</protein> by <protein>HIV protease</protein> appears unlikely to have a significant effect on virus expression or T cell function .