However , in either EL-4 ( T ) cells or S194 cells , both lower-affinity sites can be significantly induced by the tax gene product of human T-cell leukemia virus type I , showing that NF-kappa B activity can be modulated even in a B-cell line that constitutively expresses this factor .

However , in either <cell_line>EL-4 ( T ) cells</cell_line> or <cell_line>S194 cells</cell_line> , both lower-affinity sites can be significantly induced by the <protein>tax gene product</protein> of human T-cell leukemia virus type I , showing that <protein>NF-kappa B</protein> activity can be modulated even in a <cell_line>B-cell line</cell_line> that constitutively expresses this factor .


Specific depletion of the B-cell population induced by aberrant expression of human interferon regulatory factor 1 gene in transgenic mice .

Specific depletion of the <cell_line>B-cell population</cell_line> induced by aberrant expression of <dna>human interferon regulatory factor 1 gene</dna> in transgenic mice .


Interferons ( IFNs ) are well known both as antiviral proteins and as potent regulators of cell growth and differentiation .

<protein>Interferons</protein> ( <protein>IFNs</protein> ) are well known both as <protein>antiviral proteins</protein> and as potent regulators of cell growth and differentiation .


In fact , IFNs inhibit growth of various normal and transformed cell types .

In fact , <protein>IFNs</protein> inhibit growth of various <cell_type>normal</cell_type> and <cell_type>transformed cell types</cell_type> .


Previously , a nuclear factor , IRF-1 ( interferon regulatory factor 1 ) , which binds to type I IFN and some IFN-inducible gene promoters , was identified and cloned .

Previously , a <protein>nuclear factor</protein> , <protein>IRF-1</protein> ( <protein>interferon regulatory factor 1</protein> ) , which binds to <dna>type I IFN</dna> and some <dna>IFN-inducible gene promoters</dna> , was identified and cloned .


Since the IRF-1 gene is both virus and IFN inducible , an intriguing issue is raised as to whether the IRF-1 gene is functioning in IFN -mediated regulation of cell growth and differentiation .

Since the <protein>IRF-1</protein> gene is both virus and <protein>IFN</protein> inducible , an intriguing issue is raised as to whether the <dna>IRF-1 gene</dna> is functioning in <protein>IFN</protein> -mediated regulation of cell growth and differentiation .


In this study , we generated transgenic mice carrying the human IRF-1 gene linked to the human immunoglobulin heavy-chain enhancer .

In this study , we generated transgenic mice carrying the <dna>human IRF-1 gene</dna> linked to the <dna>human immunoglobulin heavy-chain enhancer</dna> .


In the transgenic mice , all the lymphoid tissues examined showed a dramatic reduction in the number of B lymphocytes ( B cells ) .

In the transgenic mice , all the lymphoid tissues examined showed a dramatic reduction in the number of <cell_type>B lymphocytes</cell_type> ( <cell_type>B cells</cell_type> ) .


Preparation and analysis of bone marrow cells from the chimeric mice indicated that the bone marrow is the effective site for specific depletion of the B-cell population .

Preparation and analysis of <cell_type>bone marrow cells</cell_type> from the chimeric mice indicated that the bone marrow is the effective site for specific depletion of the <cell_type>B-cell population</cell_type> .


In fact , transgenic bone marrow cells cocultured with a bone marrow-derived stromal cell line revealed an altered B-cell maturation pattern .

In fact , <cell_line>transgenic bone marrow cells</cell_line> cocultured with a <cell_line>bone marrow-derived stromal cell line</cell_line> revealed an altered <cell_type>B-cell</cell_type> maturation pattern .


Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein .

Characterization of a <protein>cofactor</protein> that regulates dimerization of a <protein>mammalian homeodomain protein</protein> .


Dimerization among transcription factors has become a recurrent theme in the regulation of eukaryotic gene expression .

Dimerization among <protein>transcription factors</protein> has become a recurrent theme in the regulation of eukaryotic gene expression .


Hepatocyte nuclear factor-1 alpha ( HNF-1 alpha ) is a homeodomain-containing protein that functions as a dimer .

<protein>Hepatocyte nuclear factor-1 alpha</protein> ( <protein>HNF-1 alpha</protein> ) is a <protein>homeodomain-containing protein</protein> that functions as a <protein>dimer</protein> .


A dimerization cofactor of HNF-1 alpha ( DCoH ) was identified that displayed a restricted tissue distribution and did not bind to DNA , but , rather , selectively stabilized HNF-1 alpha dimers .

A <protein>dimerization cofactor</protein> of <protein>HNF-1 alpha</protein> ( <protein>DCoH</protein> ) was identified that displayed a restricted tissue distribution and did not bind to DNA , but , rather , selectively stabilized <protein>HNF-1 alpha dimers</protein> .


The formation of a stable tetrameric DCoH-HNF-1 alpha complex , which required the dimerization domain of HNF-1 alpha , did not change the DNA binding characteristics of HNF-1 alpha , but enhanced its transcriptional activity .

The formation of a stable <protein>tetrameric DCoH-HNF-1 alpha complex</protein> , which required the <protein>dimerization domain</protein> of <protein>HNF-1 alpha</protein> , did not change the DNA binding characteristics of <protein>HNF-1 alpha</protein> , but enhanced its transcriptional activity .


However , DCoH did not confer transcriptional activation to the GAL4 DNA binding domain .

However , <protein>DCoH</protein> did not confer transcriptional activation to the <protein>GAL4 DNA binding domain</protein> .


These results indicate that DCoH regulates formation of transcriptionally active tetrameric complexes and may contribute to the developmental specificity of the complex .

These results indicate that <protein>DCoH</protein> regulates formation of transcriptionally active <protein>tetrameric complexes</protein> and may contribute to the developmental specificity of the <protein>complex</protein> .


Glucocorticoid resistance in chronic asthma .


Glucocorticoid pharmacokinetics , glucocorticoid receptor characteristics , and inhibition of peripheral blood T cell proliferation by glucocorticoids in vitro .

Glucocorticoid pharmacokinetics , <protein>glucocorticoid receptor</protein> characteristics , and inhibition of <cell_type>peripheral blood T cell</cell_type> proliferation by glucocorticoids in vitro .


A total of 37 chronic , severe , nonsmoking asthmatic patients with documented reversible airways obstruction were classified as glucocorticoid-sensitive or -resistant on the basis of changes in FEV1 , FVC , and peak expiratory flow ( PEF ) after oral prednisolone .


The resistant patients showed no significant improvements in airflow limitation .


Phytohemagglutinin ( PHA ) -induced proliferation of peripheral blood T lymphocytes from the sensitive but not the resistant asthmatic patients was significantly ( p less than 0.01 ) inhibited by dexamethasone ( 10 ( -7 ) mol/L ) , reflecting a shift of the dose-response curve .

<protein>Phytohemagglutinin</protein> ( <protein>PHA</protein> ) -induced proliferation of <cell_type>peripheral blood T lymphocytes</cell_type> from the sensitive but not the resistant asthmatic patients was significantly ( p less than 0.01 ) inhibited by dexamethasone ( 10 ( -7 ) mol/L ) , reflecting a shift of the dose-response curve .


When all the asthmatic patients were analyzed together , there was a significant correlation between the degree of sensitivity of T cells to dexamethasone and the clinical responsiveness to prednisolone ( p less than 0.01 ) .

When all the asthmatic patients were analyzed together , there was a significant correlation between the degree of sensitivity of <cell_type>T cells</cell_type> to dexamethasone and the clinical responsiveness to prednisolone ( p less than 0.01 ) .


No differences were observed between six of the sensitive and resistant patients in the clearance of plasma prednisolone derived from orally administered prednisone .


Peripheral blood mononuclear cell glucocorticoid receptors were also characterized in five sensitive and seven resistant patients .

<protein>Peripheral blood mononuclear cell glucocorticoid receptors</protein> were also characterized in five sensitive and seven resistant patients .


The numbers and binding affinities of these receptors could not account for the observed difference in the susceptibility of these cells to functional inhibition by dexamethasone in vitro .

The numbers and binding affinities of these <protein>receptors</protein> could not account for the observed difference in the susceptibility of these cells to functional inhibition by dexamethasone in vitro .


These results suggest that clinical glucocorticoid resistance in chronic asthma does not reflect abnormal glucocorticoid clearance but may be due at least partly to a relative insensitivity of T lymphocytes to glucocorticoids .

These results suggest that clinical glucocorticoid resistance in chronic asthma does not reflect abnormal glucocorticoid clearance but may be due at least partly to a relative insensitivity of <cell_type>T lymphocytes</cell_type> to glucocorticoids .


This lack of sensitivity is unexplained but is not attributable to abnormalities of cellular glucocorticoid receptors .

This lack of sensitivity is unexplained but is not attributable to abnormalities of <protein>cellular glucocorticoid receptors</protein> .


Inhibition of phorbol ester-induced monocytic differentiation by dexamethasone is associated with down-regulation of c-fos and c-jun ( AP-1 ) .

Inhibition of phorbol ester-induced monocytic differentiation by dexamethasone is associated with down-regulation of <dna>c-fos</dna> and <dna>c-jun</dna> ( <dna>AP-1</dna> ) .


Previous studies have shown that treatment of human myeloid leukemia cells with 12-O-tetradecanoylphorbol-13-acetate ( TPA ) is associated with induction of monocytic differentiation and expression of the c-jun and c-fos early response genes .

Previous studies have shown that treatment of <cell_type>human myeloid leukemia cells</cell_type> with 12-O-tetradecanoylphorbol-13-acetate ( TPA ) is associated with induction of monocytic differentiation and expression of the <dna>c-jun and c-fos early response genes</dna> .


The present work demonstrates that the glucocorticoid dexamethasone inhibits TPA-induced increases in c-jun and c-fos mRNA levels in U-937 leukemia cells .

The present work demonstrates that the glucocorticoid dexamethasone inhibits TPA-induced increases in c-jun and c-fos mRNA levels in <cell_line>U-937 leukemia cells</cell_line> .


These findings were associated with a block in appearance of the monocytic phenotype , including inhibition of TPA-induced increases in lamin A , lamin C , and vimentin transcripts .

These findings were associated with a block in appearance of the <cell_type>monocytic phenotype</cell_type> , including inhibition of TPA-induced increases in <rna>lamin A , lamin C , and vimentin transcripts</rna> .


Other studies have demonstrated that TPA-induced monocytic differentiation and expression of the c-jun and c-fos genes in myeloid leukemia cells are regulated by protein kinase C ( PKC ) .

Other studies have demonstrated that TPA-induced monocytic differentiation and expression of the <dna>c-jun</dna> and <dna>c-fos genes</dna> in <cell_type>myeloid leukemia cells</cell_type> are regulated by <protein>protein kinase C</protein> ( <protein>PKC</protein> ) .


The finding that dexamethasone has no effect on TPA-induced activation of PKC suggests that this glucocorticoid inhibits signals downstream or parallel to this enzyme .

The finding that dexamethasone has no effect on TPA-induced activation of <protein>PKC</protein> suggests that this glucocorticoid inhibits signals downstream or parallel to this <protein>enzyme</protein> .


Nuclear run-on assays demonstrate that : ( 1 ) induction of c-jun and c-fos expression by TPA is regulated by transcriptional mechanisms , ( 2 ) TPA-induced expression of c-jun and c-fos does not require protein synthesis , and ( 3 ) TPA-induced expression of both genes is inhibited at the transcriptional level by dexamethasone .

Nuclear run-on assays demonstrate that : ( 1 ) induction of c-jun and c-fos expression by TPA is regulated by transcriptional mechanisms , ( 2 ) TPA-induced expression of <dna>c-jun</dna> and <protein>c-fos</protein> does not require protein synthesis , and ( 3 ) TPA-induced expression of both genes is inhibited at the transcriptional level by dexamethasone .


To further define the effects of dexamethasone at the molecular level , we prepared a series of deleted c-jun promoter fragments linked to the chloramphenicol acetyltransferase ( CAT ) gene .

To further define the effects of dexamethasone at the molecular level , we prepared a series of deleted <dna>c-jun promoter fragments</dna> linked to the <dna>chloramphenicol acetyltransferase ( CAT ) gene</dna> .


Increases in CAT activity during transient expression of these constructs in TPA-treated U-937 cells could be assigned to the region ( -97 to -20 ) of the promoter that contains the AP-1 binding site .

Increases in <protein>CAT</protein> activity during transient expression of these constructs in <cell_line>TPA-treated U-937 cells</cell_line> could be assigned to the region ( -97 to -20 ) of the <dna>promoter</dna> that contains the <dna>AP-1 binding site</dna> .


This induction of CAT activity was sensitive to dexamethasone .

This induction of <protein>CAT</protein> activity was sensitive to dexamethasone .


These findings suggest that dexamethasone down-regulates TPA-induced transcription of the c-jun gene during monocytic differentiation by inhibiting activation of the AP-1 site .

These findings suggest that dexamethasone down-regulates TPA-induced transcription of the <dna>c-jun</dna> gene during monocytic differentiation by inhibiting activation of the <dna>AP-1 site</dna> .


Tumor necrosis factor-alpha mRNA accumulation in human myelomonocytic cell lines .

<rna>Tumor necrosis factor-alpha mRNA</rna> accumulation in <cell_line>human myelomonocytic cell lines</cell_line> .


Role of transcriptional regulation by DNA sequence motifs and mRNA stabilization .

Role of transcriptional regulation by <dna>DNA sequence motifs</dna> and mRNA stabilization .


The cytokine TNF mediates many of the pathologic signs of cachexia , inflammation , and sepsis .

The <protein>cytokine</protein> <protein>TNF</protein> mediates many of the pathologic signs of cachexia , inflammation , and sepsis .


The current work describes the regulation of TNF in human myelomonocytic cell lines after PMA stimulation .

The current work describes the regulation of <protein>TNF</protein> in <cell_line>human myelomonocytic cell lines</cell_line> after PMA stimulation .


The cell lines exhibit a low level of constitutive TNF mRNA expression .

The <cell_line>cell lines</cell_line> exhibit a low level of constitutive <rna>TNF mRNA</rna> expression .


Within 2 to 4 h of PMA exposure , steady state levels of TNF mRNA are markedly elevated in all myelomonocytic cell lines studied .

Within 2 to 4 h of PMA exposure , steady state levels of <rna>TNF mRNA</rna> are markedly elevated in all <cell_line>myelomonocytic cell lines</cell_line> studied .


This rise is due to increased mRNA stability , which increased by almost twofold , and to an overall increase in transcription , which rises by more than sixfold .


At the level of the genomic TNF gene , a DNase I hypersensitive site is detected within the TNF promoter between -200 to -100 bp relative to the transcription initiation site .

At the level of the <dna>genomic TNF gene</dna> , a <dna>DNase I hypersensitive site</dna> is detected within the <dna>TNF promoter</dna> between -200 to -100 bp relative to the <dna>transcription initiation site</dna> .


Although absent in nonexpressing erythroleukemia cell lines , the DNase I site is present in uninduced myelomonocytic cell lines and is not changed after PMA induction .

Although absent in <cell_line>nonexpressing erythroleukemia cell lines</cell_line> , the <dna>DNase I site</dna> is present in <cell_line>uninduced myelomonocytic cell lines</cell_line> and is not changed after PMA induction .


The PMA induction of c-fos mRNA correlated well with TNF gene induction ; expression of genes encoding other proteins in the AP-1 complex ( junB and junD ) were also induced by PMA .

The PMA induction of <rna>c-fos mRNA</rna> correlated well with <protein>TNF</protein> gene induction ; expression of genes encoding other proteins in the <protein>AP-1 complex</protein> ( <protein>junB</protein> and <protein>junD</protein> ) were also induced by PMA .


The nuclear extracts from resting and induced ML-1 cells contain proteins binding specifically to the AP-1 , AP-2 , and NF kappa B sequence located within the TNF promoter .

The nuclear extracts from resting and <cell_line>induced ML-1 cells</cell_line> contain proteins binding specifically to the <dna>AP-1 , AP-2 , and NF kappa B sequence</dna> located within the <dna>TNF promoter</dna> .


PMA induction increases the level of a number of specific binding complexes relative to the resting cells .

PMA induction increases the level of a number of <protein>specific binding complexes</protein> relative to the <cell_type>resting cells</cell_type> .


The regulatory mechanisms of the human and murine TNF genes are discussed .

The regulatory mechanisms of the <dna>human and murine TNF genes</dna> are discussed .


Enhancement of human immunodeficiency virus 1 replication in monocytes by 1 , 25-dihydroxycholecalciferol .

Enhancement of human immunodeficiency virus 1 replication in <cell_type>monocytes</cell_type> by 1 , 25-dihydroxycholecalciferol .


Human immunodeficiency virus ( HIV ) expression and replication are under tight regulatory control .


We demonstrate that 1 , 25-dihydroxycholecalciferol [ 1 , 25- ( OH ) 2D3 ] enhances the replication of monocyte- and lymphocyte-tropic strains of HIV-1 up to 10 , 000-fold in monocyte cell lines , peripheral blood monocytes , and unfractionated peripheral blood mononuclear cells .

We demonstrate that 1 , 25-dihydroxycholecalciferol [ 1 , 25- ( OH ) 2D3 ] enhances the replication of monocyte- and lymphocyte-tropic strains of HIV-1 up to 10 , 000-fold in <cell_line>monocyte cell lines</cell_line> , <cell_type>peripheral blood monocytes</cell_type> , and <cell_type>unfractionated peripheral blood mononuclear cells</cell_type> .


1 , 25 ( OH ) 2D3 is therefore one of the most potent regulators of HIV-1 replication described to date .


Precursors of 1 , 25 ( OH ) 2D3 enhance HIV-1 replication in proportion to their affinity for the 1 , 25 ( OH ) 2D3 intracellular receptor , suggesting that 1 , 25 ( OH ) 2D3 influences HIV-1 replication by mechanisms involving this receptor .

Precursors of 1 , 25 ( OH ) 2D3 enhance HIV-1 replication in proportion to their affinity for the <protein>1 , 25 ( OH ) 2D3 intracellular receptor</protein> , suggesting that 1 , 25 ( OH ) 2D3 influences HIV-1 replication by mechanisms involving this receptor .


These studies may have important implications for the design of effective therapy of HIV-1 infection .


Transforming growth factor-beta suppresses human B lymphocyte Ig production by inhibiting synthesis and the switch from the membrane form to the secreted form of Ig mRNA .

<protein>Transforming growth factor-beta</protein> suppresses <protein>human B lymphocyte Ig</protein> production by inhibiting synthesis and the switch from the <rna>membrane form</rna> to the <rna>secreted form</rna> of <rna>Ig mRNA</rna> .


Transforming growth factor-beta ( TGF-beta ) inhibits B cell Ig secretion and reduces B cell membrane Ig expression .

<protein>Transforming growth factor-beta</protein> ( <protein>TGF-beta</protein> ) inhibits <cell_type>B cell</cell_type> <protein>Ig</protein> secretion and reduces <cell_type>B cell</cell_type> membrane <protein>Ig</protein> expression .


The addition of TGF-beta to human B lymphocyte cultures stimulated with Staphylococcus aureus Cowan strain I and IL-2 completely inhibited B cell Ig secretion ( greater than 90 % ) and decreased B cell surface IgM , IgD , kappa L chain , and lambda L chain expression .

The addition of <protein>TGF-beta</protein> to <cell_line>human B lymphocyte cultures</cell_line> stimulated with Staphylococcus aureus Cowan strain I and <protein>IL-2</protein> completely inhibited <cell_type>B cell</cell_type> <protein>Ig</protein> secretion ( greater than 90 % ) and decreased <cell_type>B cell</cell_type> surface IgM , IgD , kappa L chain , and lambda L chain expression .


In contrast , TGF-beta had only minimal effects on two other B cell membrane proteins , HLA-DR and CD20 .

In contrast , <protein>TGF-beta</protein> had only minimal effects on two other <protein>B cell membrane proteins</protein> , <protein>HLA-DR</protein> and <protein>CD20</protein> .


Internal labeling with [ 35S ] methionine and immunoprecipitation with anti-IgM , anti-kappa , and anti-lambda antibodies revealed a striking reduction in kappa L chain in the presence of TGF-beta .

Internal labeling with [ 35S ] methionine and immunoprecipitation with <protein>anti-IgM</protein> , <protein>anti-kappa</protein> , and <protein>anti-lambda antibodies</protein> revealed a striking reduction in <protein>kappa L chain</protein> in the presence of <protein>TGF-beta</protein> .


A less pronounced reduction in lambda L chain and microH chain was also noted .

A less pronounced reduction in <protein>lambda L chain</protein> and <protein>microH chain</protein> was also noted .


Northern blot analysis of RNA purified from B cells treated with TGF-beta for varying time intervals revealed a significant decrease in steady state kappa and lambda L chain mRNA levels .

Northern blot analysis of RNA purified from <cell_type>B cells</cell_type> treated with <protein>TGF-beta</protein> for varying time intervals revealed a significant decrease in steady state kappa and lambda L chain mRNA levels .


Furthermore , a significant decrease in the switch from the membrane forms of mu and gamma to their respective secreted forms was noted in the presence of TGF-beta .

Furthermore , a significant decrease in the switch from the <rna>membrane forms</rna> of <rna>mu</rna> and <rna>gamma</rna> to their respective <rna>secreted forms</rna> was noted in the presence of <protein>TGF-beta</protein> .


Nuclear run-on experiments demonstrated decreased transcription of kappa L chain .

Nuclear run-on experiments demonstrated decreased transcription of <protein>kappa L chain</protein> .


The effects of TGF-beta on two transcriptional regulatory factors , Oct-2 and nuclear factor ( NF ) kappa B , known to be important in Ig gene transcription were examined .

The effects of <protein>TGF-beta</protein> on two <protein>transcriptional regulatory factors</protein> , <protein>Oct-2</protein> and <protein>nuclear factor ( NF ) kappa B</protein> , known to be important in <protein>Ig</protein> gene transcription were examined .


Oct-2 mRNA levels and both Oct-2 and NF-kappa B proteins in nuclear extracts were not altered by treatment with TGF-beta .

<rna>Oct-2 mRNA</rna> levels and both <protein>Oct-2</protein> and <protein>NF-kappa B proteins</protein> in nuclear extracts were not altered by treatment with <protein>TGF-beta</protein> .


In contrast , levels of the transcriptional factor AP-1 , which is not known to be important in B cell Ig production , were reduced by TGF-beta .

In contrast , levels of the <protein>transcriptional factor AP-1</protein> , which is not known to be important in <cell_type>B cell</cell_type> <protein>Ig</protein> production , were reduced by <protein>TGF-beta</protein> .


These findings demonstrate that TGF-beta decreases B lymphocyte Ig secretion by inhibiting the synthesis of Ig mRNA and inhibiting the switch from the membrane form to the secreted forms of mu and gamma mRNA .

These findings demonstrate that <protein>TGF-beta</protein> decreases B lymphocyte <protein>Ig</protein> secretion by inhibiting the synthesis of <rna>Ig mRNA</rna> and inhibiting the switch from the <rna>membrane form</rna> to the <rna>secreted forms</rna> of <rna>mu and gamma mRNA</rna> .


The mechanism by which TGF-beta inhibits Ig chain synthesis is unclear although it does not involve inhibition of the binding of NF-kappa B or Oct-2 to their respective target sequences .

The mechanism by which <protein>TGF-beta</protein> inhibits Ig chain synthesis is unclear although it does not involve inhibition of the binding of <protein>NF-kappa B</protein> or <protein>Oct-2</protein> to their respective target sequences .


Murine and human T-lymphocyte GATA-3 factors mediate transcription through a cis-regulatory element within the human T-cell receptor delta gene enhancer .

<protein>Murine and human T-lymphocyte GATA-3 factors</protein> mediate transcription through a <dna>cis-regulatory element</dna> within the <dna>human T-cell receptor delta gene enhancer</dna> .


A family of transcriptional activators has recently been identified in chickens ; these transcriptional activators recognize a common consensus motif ( WGATAR ) through a conserved C4 zinc finger DNA-binding domain .

A family of <protein>transcriptional activators</protein> has recently been identified in chickens ; these <protein>transcriptional activators</protein> recognize a common <dna>consensus motif</dna> ( <dna>WGATAR</dna> ) through a conserved <protein>C4 zinc finger DNA-binding domain</protein> .


One of the members of this multigene family , cGATA-3 , is most abundantly expressed in the T-lymphocyte cell lineage .

One of the members of this multigene family , <protein>cGATA-3</protein> , is most abundantly expressed in the <cell_type>T-lymphocyte cell lineage</cell_type> .


Analysis of human and murine GATA-3 factors shows a striking degree of amino acid sequence identity and similar patterns of tissue specificity of expression in these three organisms .

Analysis of <protein>human and murine GATA-3 factors</protein> shows a striking degree of amino acid sequence identity and similar patterns of tissue specificity of expression in these three organisms .


The murine and human factors are abundantly expressed in a variety of human and murine T-cell lines and can activate transcription through a tissue-specific GATA-binding site identified within the human T-cell receptor delta gene enhancer .

The <protein>murine and human factors</protein> are abundantly expressed in a variety of <cell_line>human and murine T-cell lines</cell_line> and can activate transcription through a <dna>tissue-specific GATA-binding site</dna> identified within the <dna>human T-cell receptor delta gene enhancer</dna> .


We infer that the murine and human GATA-3 proteins play a central and highly conserved role in vertebrate T-cell-specific transcriptional regulation .

We infer that the <protein>murine and human GATA-3 proteins</protein> play a central and highly conserved role in vertebrate T-cell-specific transcriptional regulation .


Processing of the precursor of NF-kappa B by the HIV-1 protease during acute infection .

Processing of the precursor of <protein>NF-kappa B</protein> by the <protein>HIV-1 protease</protein> during acute infection .


Transcription of the human immunodeficiency virus type-1 ( HIV-1 ) genome is regulated in part by cellular factors and is stimulated by activation of latently infected T cells .

Transcription of the <dna>human immunodeficiency virus type-1 ( HIV-1 ) genome</dna> is regulated in part by <protein>cellular factors</protein> and is stimulated by activation of <cell_type>latently infected T cells</cell_type> .


T-cell activation also correlates with the induction of the factor NF-kappa B which binds to two adjacent sites in the HIV-1 long terminal repeat .

T-cell activation also correlates with the induction of the factor <protein>NF-kappa B</protein> which binds to two adjacent sites in the <dna>HIV-1 long terminal repeat</dna> .


This factor consists of two DNA-binding subunits of relative molecular mass 50 , 000 ( 50K ) associated with two 65K subunits .

This factor consists of two <protein>DNA-binding subunits</protein> of relative molecular mass 50 , 000 ( 50K ) associated with two <protein>65K subunits</protein> .


It is located in the nucleus in mature B cells , but is present in other cell types as an inactive cytoplasmic complex .

It is located in the nucleus in <cell_type>mature B cells</cell_type> , but is present in other cell types as an <protein>inactive cytoplasmic complex</protein> .


External stimuli , including those that activate T cells , result in nuclear translocation of active NF-kappa B .

External stimuli , including those that activate <cell_type>T cells</cell_type> , result in nuclear translocation of active <protein>NF-kappa B</protein> .


The cloning of the complementary DNA for the 50K subunit helped to identify an exclusively cytoplasmic 105K precursor ( p105 ) ( V.B. , P.K. and A.I. , manuscript submitted ) .

The cloning of the <dna>complementary DNA</dna> for the <protein>50K subunit</protein> helped to identify an exclusively <protein>cytoplasmic 105K precursor</protein> ( <protein>p105</protein> ) ( V.B. , P.K. and A.I. , manuscript submitted ) .


The expression of active NF-kappa B might therefore also be regulated by the extent of processing of p105 .

The expression of active <protein>NF-kappa B</protein> might therefore also be regulated by the extent of processing of <protein>p105</protein> .


Because HIV-1 requires active NF-kappa B for efficient transcription , we tested the effect of HIV-1 infection on the processing of the human 105K precursor .

Because HIV-1 requires active <protein>NF-kappa B</protein> for efficient transcription , we tested the effect of HIV-1 infection on the processing of the <protein>human 105K precursor</protein> .


We show here that the HIV-1 protease can process p105 and increases levels of active nuclear NF-kappa B complex .

We show here that the HIV-1 protease can process <protein>p105</protein> and increases levels of active <protein>nuclear NF-kappa B complex</protein> .


1 , 25-Dihydroxyvitamin D3 receptor RNA : expression in hematopoietic cells .

<rna>1 , 25-Dihydroxyvitamin D3 receptor RNA</rna> : expression in <cell_type>hematopoietic cells</cell_type> .


1 , 25-Dihydroxyvitamin D3 [ 1 , 25 ( OH ) 2D3 ] induces differentiation and inhibits proliferation of myeloid leukemic cells from various lines and patients ; these effects are probably mediated through the 1 , 25 ( OH ) 2D3 receptor .

1 , 25-Dihydroxyvitamin D3 [ 1 , 25 ( OH ) 2D3 ] induces differentiation and inhibits proliferation of <cell_type>myeloid leukemic cells</cell_type> from various lines and patients ; these effects are probably mediated through the <protein>1 , 25 ( OH ) 2D3 receptor</protein> .


Little is known of expression of 1 , 25 ( OH ) 2D3 receptor RNA in hematopoietic cells .

Little is known of expression of <rna>1 , 25 ( OH ) 2D3 receptor RNA</rna> in <cell_type>hematopoietic cells</cell_type> .


We examined the expression and modulation of expression of 1 , 25 ( OH ) 2D3 receptor RNA in various proliferating and nonproliferating hematopoietic cells .

We examined the expression and modulation of expression of <rna>1 , 25 ( OH ) 2D3 receptor RNA</rna> in various <cell_type>proliferating and nonproliferating hematopoietic cells</cell_type> .


Constitutive expression of 1 , 25 ( OH ) 2D3 receptor RNA was detected in various kinds of hematopoietic cells , including macrophages and activated T lymphocytes , as well as in cell lines KG-1 ( myeloblasts ) , HL-60 ( promyelocytes ) , ML-3 ( myelomonoblasts ) , U937 , THP-1 ( monoblasts ) , K562 ( erythroblasts ) , and S-LB1 ( HTLV-1-transfected T lymphocytes ) .

Constitutive expression of <rna>1 , 25 ( OH ) 2D3 receptor RNA</rna> was detected in various kinds of <cell_type>hematopoietic cells</cell_type> , including macrophages and activated <cell_type>T lymphocytes</cell_type> , as well as in cell lines <cell_line>KG-1</cell_line> ( <cell_line>myeloblasts</cell_line> ) , <cell_line>HL-60</cell_line> ( <cell_line>promyelocytes</cell_line> ) , <cell_line>ML-3</cell_line> ( <cell_line>myelomonoblasts</cell_line> ) , <cell_line>U937</cell_line> , <cell_line>THP-1</cell_line> ( <cell_line>monoblasts</cell_line> ) , <cell_line>K562</cell_line> ( <cell_line>erythroblasts</cell_line> ) , and <cell_line>S-LB1</cell_line> ( <cell_line>HTLV-1-transfected T lymphocytes</cell_line> ) .


Receptor transcripts were 4.6 kilobases ( kb ) , and no variant sizes were observed .

<rna>Receptor transcripts</rna> were 4.6 kilobases ( kb ) , and no variant sizes were observed .


All cell lines examined in this group also expressed 1 , 25 ( OH ) 2D3 receptors .

All cell lines examined in this group also expressed <protein>1 , 25 ( OH ) 2D3 receptors</protein> .


Most B lymphocyte lines expressed negligible levels of 1 , 25 ( OH ) 2D3 receptor RNA and protein ; however ; analysis of a lymphoid/myeloid somatic hybrid suggested that suppression of expression of 1 , 25 ( OH ) 2D3 receptor RNA in B lymphocytes may be a dominant characteristic .

Most <cell_line>B lymphocyte lines</cell_line> expressed negligible levels of <rna>1 , 25 ( OH ) 2D3 receptor RNA</rna> and protein ; however ; analysis of a <cell_line>lymphoid/myeloid somatic hybrid</cell_line> suggested that suppression of expression of <rna>1 , 25 ( OH ) 2D3 receptor RNA</rna> in <cell_type>B lymphocytes</cell_type> may be a dominant characteristic .


HL-60 cells were cultured with 10 ( -7 ) mol/L 1 , 25 ( OH ) 2D3 for 24 to 72 hours , and levels of expression of 1 , 25 ( OH ) 2D3 receptor and its RNA were examined .

<cell_line>HL-60 cells</cell_line> were cultured with 10 ( -7 ) mol/L 1 , 25 ( OH ) 2D3 for 24 to 72 hours , and levels of expression of <protein>1 , 25 ( OH ) 2D3 receptor</protein> and its RNA were examined .


Levels of RNA coding for the receptor were not modulated by exposure to high levels of ligand .

Levels of RNA coding for the <protein>receptor</protein> were not modulated by exposure to high levels of ligand .


Levels of occupied 1 , 25 ( OH ) 2D3 receptor protein increased in these HL-60 cells ; but the total number of 1 , 25 ( OH ) 2D3 receptors decreased about 50 % at 24 hours and returned toward normal at 72 hours .

Levels of occupied <protein>1 , 25 ( OH ) 2D3 receptor protein</protein> increased in these <cell_line>HL-60 cells</cell_line> ; but the total number of <protein>1 , 25 ( OH ) 2D3 receptors</protein> decreased about 50 % at 24 hours and returned toward normal at 72 hours .


Steady-state levels of 1 , 25 ( OH ) 2D3 receptor RNA were not affected by terminal differentiation of HL-60 toward either granulocytes or macrophages .

Steady-state levels of <rna>1 , 25 ( OH ) 2D3 receptor RNA</rna> were not affected by terminal differentiation of <cell_line>HL-60</cell_line> toward either <cell_type>granulocytes</cell_type> or <cell_type>macrophages</cell_type> .


Nondividing macrophages from normal individuals also expressed 1 , 25 ( OH ) 2D3 receptor RNA .

Nondividing <cell_type>macrophages</cell_type> from normal individuals also expressed <rna>1 , 25 ( OH ) 2D3 receptor RNA</rna> .


In contrast , nondividing peripheral blood lymphocytes from normal individuals did not express 1 , 25 ( OH ) 2D3 receptor RNA ; with stimulation of proliferation of these cells , accumulation of 1 , 25 ( OH ) 2D3 receptor RNA increased markedly .

In contrast , <cell_type>nondividing peripheral blood lymphocytes</cell_type> from normal individuals did not express <rna>1 , 25 ( OH ) 2D3 receptor RNA</rna> ; with stimulation of proliferation of these cells , accumulation of <rna>1 , 25 ( OH ) 2D3 receptor RNA</rna> increased markedly .


Half-life ( t1/2 ) of 1 , 25 ( OH ) 2D3 receptor RNA in T lymphocytes was short ( 1 hour ) as determined by measuring decay of the message after addition of actinomycin D .

Half-life ( t1/2 ) of <rna>1 , 25 ( OH ) 2D3 receptor RNA</rna> in <cell_type>T lymphocytes</cell_type> was short ( 1 hour ) as determined by measuring decay of the message after addition of actinomycin D .


Consistent with this short t1/2 , accumulation of 1 , 25 ( OH ) 2D3 receptor RNA increased in cells as their protein synthesis was inhibited .

Consistent with this short t1/2 , accumulation of <rna>1 , 25 ( OH ) 2D3 receptor RNA</rna> increased in cells as their protein synthesis was inhibited .


Further studies are required to understand the physiologic role of 1 , 25 ( OH ) 2D3 receptors in myeloid cells and proliferating T lymphocytes .

Further studies are required to understand the physiologic role of <protein>1 , 25 ( OH ) 2D3 receptors</protein> in <cell_type>myeloid cells</cell_type> and <cell_type>proliferating T lymphocytes</cell_type> .


Expression of c-jun , jun B and jun D proto-oncogenes in human peripheral-blood granulocytes .

Expression of <dna>c-jun , jun B and jun D proto-oncogenes</dna> in <cell_type>human peripheral-blood granulocytes</cell_type> .


We have found that purified human peripheral-blood granulocytes express constitutively significant levels of proto-oncogenes c-jun , jun B and jun D mRNA .

We have found that <cell_type>purified human peripheral-blood granulocytes</cell_type> express constitutively significant levels of <dna>proto-oncogenes</dna> <rna>c-jun , jun B and jun D mRNA</rna> .


Upon functional activation of granulocytes by 4 beta-phorbol 12-myristate 13-acetate ( PMA ) , the levels of c-jun , jun B and jun D transcripts were increased .

Upon functional activation of <cell_type>granulocytes</cell_type> by 4 beta-phorbol 12-myristate 13-acetate ( PMA ) , the levels of <rna>c-jun , jun B and jun D transcripts</rna> were increased .


The three jun genes showed a similar time course in their induction by PMA , maximal mRNA levels being reached after 60 min of induction .

The three <dna>jun genes</dna> showed a similar time course in their induction by PMA , maximal mRNA levels being reached after 60 min of induction .


These results suggest that expression of c-jun , jun B and jun D genes might be involved in terminal granulocyte differentiation or in regulating granulocyte functionality .

These results suggest that expression of <dna>c-jun</dna> , <dna>jun B</dna> and <dna>jun D genes</dna> might be involved in <cell_type>terminal granulocyte</cell_type> differentiation or in regulating <cell_type>granulocyte</cell_type> functionality .


The 29-kDa proteins phosphorylated in thrombin-activated human platelets are forms of the estrogen receptor-related 27-kDa heat shock protein .

The <protein>29-kDa proteins</protein> phosphorylated in <cell_line>thrombin-activated human platelets</cell_line> are forms of the <protein>estrogen receptor-related 27-kDa heat shock protein</protein> .


Thrombin plays a critical role in platelet activation , hemostasis , and thrombosis .

<protein>Thrombin</protein> plays a critical role in platelet activation , hemostasis , and thrombosis .


Cellular activation by thrombin leads to the phosphorylation of multiple proteins , most of which are unidentified .

Cellular activation by thrombin leads to the phosphorylation of <protein>multiple proteins</protein> , most of which are unidentified .


We have characterized several 29-kDa proteins that are rapidly phosphorylated following exposure of intact human platelets to thrombin .

We have characterized several <protein>29-kDa proteins</protein> that are rapidly phosphorylated following exposure of <cell_type>intact human platelets</cell_type> to <protein>thrombin</protein> .


A murine monoclonal antibody raised to an unidentified estrogen receptor-related 29-kDa protein selectively recognized these proteins as well as a more basic , unphosphorylated 27-kDa protein .

A <protein>murine monoclonal antibody</protein> raised to an <protein>unidentified estrogen receptor-related 29-kDa protein</protein> selectively recognized these proteins as well as a more basic , <protein>unphosphorylated 27-kDa protein</protein> .


Cellular activation by thrombin led to a marked shift in the proportion of protein from the 27-kDa unphosphorylated form to the 29-kDa phosphoprotein species .

Cellular activation by <protein>thrombin</protein> led to a marked shift in the proportion of protein from the <protein>27-kDa unphosphorylated form</protein> to the <protein>29-kDa phosphoprotein species</protein> .


Using this antibody , we isolated and sequenced a human cDNA clone encoding a protein that was identical to the mammalian 27-kDa heat shock protein ( HSP27 ) , a protein of uncertain function that is known to be phosphorylated to several forms and to be transcriptionally induced by estrogen .

Using this antibody , we isolated and sequenced a human <dna>cDNA clone</dna> encoding a protein that was identical to the <protein>mammalian 27-kDa heat shock protein</protein> ( <protein>HSP27</protein> ) , a protein of uncertain function that is known to be phosphorylated to several forms and to be transcriptionally induced by estrogen .


The 29-kDa proteins were confirmed to be phosphorylated forms of HSP27 by immunoprecipitation studies .

The <protein>29-kDa proteins</protein> were confirmed to be phosphorylated forms of <protein>HSP27</protein> by immunoprecipitation studies .


Thus , the `` estrogen receptor-related protein '' is HSP27 , and the three major 29-kDa proteins phosphorylated in thrombin-activated platelets are forms of HSP27 .

Thus , the `` estrogen receptor-related protein '' is <protein>HSP27</protein> , and the three major <protein>29-kDa proteins</protein> phosphorylated in <cell_type>thrombin-activated platelets</cell_type> are forms of <protein>HSP27</protein> .


These data suggest a role for HSP27 in the signal transduction events of platelet activation .

These data suggest a role for <protein>HSP27</protein> in the signal transduction events of <cell_type>platelet</cell_type> activation .


Isolation of a candidate repressor/activator , NF-E1 ( YY-1 , delta ) , that binds to the immunoglobulin kappa 3 ' enhancer and the immunoglobulin heavy-chain mu E1 site .

Isolation of a candidate repressor/activator , <protein>NF-E1</protein> ( <protein>YY-1</protein> , <protein>delta</protein> ) , that binds to the <dna>immunoglobulin kappa 3 ' enhancer</dna> and the <dna>immunoglobulin heavy-chain mu E1 site</dna> .


We have determined that the developmental control of immunoglobulin kappa 3 ' enhancer ( kappa E3 ' ) activity is the result of the combined influence of positive- and negative-acting elements .

We have determined that the developmental control of <dna>immunoglobulin kappa 3 ' enhancer</dna> ( <dna>kappa E3 '</dna> ) activity is the result of the combined influence of <dna>positive- and negative-acting elements</dna> .


We show that a central core in the kappa E3 ' enhancer is active at the pre-B-cell stage but is repressed by flanking negative-acting elements .

We show that a central core in the <dna>kappa E3 ' enhancer</dna> is active at the pre-B-cell stage but is repressed by <dna>flanking negative-acting elements</dna> .


The negative-acting sequences repress enhancer activity in a position- and orientation-independent manner at the pre-B-cell stage .

The <dna>negative-acting sequences</dna> repress enhancer activity in a position- and orientation-independent manner at the pre-B-cell stage .


We have isolated a human cDNA clone encoding a zinc finger protein ( NF-E1 ) that binds to the negative-acting segment of the kappa E3 ' enhancer .

We have isolated a <dna>human cDNA clone</dna> encoding a <protein>zinc finger protein</protein> ( <protein>NF-E1</protein> ) that binds to the <dna>negative-acting segment</dna> of the <dna>kappa E3 ' enhancer</dna> .


This protein also binds to the immunoglobulin heavy-chain enhancer mu E1 site .

This protein also binds to the <dna>immunoglobulin heavy-chain enhancer mu E1 site</dna> .


NF-E1 is encoded by the same gene as the YY-1 protein , which binds to the adeno-associated virus P5 promoter .

<protein>NF-E1</protein> is encoded by the same gene as the <protein>YY-1 protein</protein> , which binds to the <dna>adeno-associated virus P5 promoter</dna> .


NF-E1 is also the human homologue of the mouse delta protein , which binds to ribosomal protein gene promoters .

<protein>NF-E1</protein> is also the <protein>human homologue</protein> of the <dna>mouse delta protein</dna> , which binds to <dna>ribosomal protein gene promoters</dna> .


The predicted amino acid sequence of this protein contains features characteristic of transcriptional activators as well as transcriptional repressors .

The predicted amino acid sequence of this protein contains features characteristic of <protein>transcriptional activators</protein> as well as <protein>transcriptional repressors</protein> .


Cotransfection studies with this cDNA indicate that it can repress basal promoter activity .

Cotransfection studies with this <dna>cDNA</dna> indicate that it can repress <dna>basal promoter</dna> activity .


The apparent dual function of this protein is discussed .


A human putative lymphocyte G0/G1 switch gene containing a CpG-rich island encodes a small basic protein with the potential to be phosphorylated .

A <dna>human putative lymphocyte G0/G1 switch gene</dna> containing a <dna>CpG-rich island</dna> encodes a <protein>small basic protein</protein> with the potential to be phosphorylated .


Genes actively involved in the G0/G1 switch ( G0S genes ) may be differentially expressed during the lectin -induced switch of lymphocytes from the G0 to the G1 phases of the cell cycle .

Genes actively involved in the <dna>G0/G1 switch</dna> ( <rna>G0S genes</rna> ) may be differentially expressed during the <protein>lectin</protein> -induced switch of <cell_type>lymphocytes</cell_type> from the G0 to the G1 phases of the cell cycle .


This paper presents studies of G0S2 , a member of a set of putative G0S genes , for which cDNAs were cloned and selected on the basis of differential cDNA hybridization .

This paper presents studies of <dna>G0S2</dna> , a member of a set of putative <rna>G0S genes</rna> , for which <dna>cDNAs</dna> were cloned and selected on the basis of differential cDNA hybridization .


G0S2 mRNA increases transiently within 1-2 hr of the addition of lectin or cycloheximide to cultured blood mononuclear cells .

<rna>G0S2 mRNA</rna> increases transiently within 1-2 hr of the addition of <protein>lectin</protein> or cycloheximide to <cell_type>cultured blood mononuclear cells</cell_type> .


Comparison of a nearly full-length cDNA sequence with the corresponding genomic sequence reveals one small intron and an open reading frame in the second exon .

Comparison of a <dna>nearly full-length cDNA sequence</dna> with the corresponding <dna>genomic sequence</dna> reveals one small intron and an <dna>open reading frame</dna> in the second <dna>exon</dna> .


The derived 103-amino-acid basic protein has two potential alpha-helical domains separated by a hydrophobic region with the potential to generate turns and assume a beta-sheet conformation .

The derived <protein>103-amino-acid basic protein</protein> has two potential <protein>alpha-helical domains</protein> separated by a <protein>hydrophobic region</protein> with the potential to generate turns and assume a beta-sheet conformation .


Consistent with involvement in the G0/G1 switch , the protein contains potential sites for phosphorylation by protein kinase C and casein kinase II .

Consistent with involvement in the <dna>G0/G1 switch</dna> , the protein contains potential sites for phosphorylation by <protein>protein kinase C</protein> and <protein>casein kinase II</protein> .


The gene contains a CpG-rich island suggesting expression in the germ line .

The gene contains a <protein>CpG-rich island</protein> suggesting expression in the germ line .


An upstream segment contains tandem dinucleotide repeats ( CT ) 19/ ( CA ) 16 .

An <dna>upstream segment</dna> contains <dna>tandem dinucleotide repeats</dna> <dna>( CT ) 19/ ( CA ) 16</dna> .


There is a suitably located TATA box , but potential sites for CCAAT-box binding factors are far upstream , embedded in a 42-nucleotide repeat element .

There is a suitably located <dna>TATA box</dna> , but potential sites for <protein>CCAAT-box binding factors</protein> are far upstream , embedded in a <dna>42-nucleotide repeat element</dna> .


Potential sites for transcription factors AP1 , AP2 , and AP3 are consistent with rapid transcriptional activation in response to inducing agents .

Potential sites for <protein>transcription factors</protein> <protein>AP1</protein> , <protein>AP2</protein> , and <protein>AP3</protein> are consistent with rapid transcriptional activation in response to inducing agents .


USF-related transcription factor , HIV-TF1 , stimulates transcription of human immunodeficiency virus-1 .

<protein>USF-related transcription factor</protein> , <protein>HIV-TF1</protein> , stimulates transcription of human immunodeficiency virus-1 .


The transcription factor HIV-TF1 , which binds to a region about 60 bp upstream from the enhancer of the human immunodeficiency virus-1 ( HIV-1 ) , was purified from human B cells .

The <protein>transcription factor</protein> <protein>HIV-TF1</protein> , which binds to a region about <dna>60 bp upstream</dna> from the enhancer of the human immunodeficiency virus-1 ( HIV-1 ) , was purified from <cell_type>human B cells</cell_type> .


HIV-TF1 had a molecular weight of 39 , 000 .

<protein>HIV-TF1</protein> had a molecular weight of 39 , 000 .


Binding of HIV-TF1 to the HIV long terminal repeat ( LTR ) activated transcription from the HIV promoter in vitro .

Binding of <protein>HIV-TF1</protein> to the <dna>HIV long terminal repeat</dna> ( <dna>LTR</dna> ) activated transcription from the <dna>HIV promoter</dna> in vitro .


The HIV-TF1-binding site in HIV LTR was similar to the site recognized by upstream stimulatory factor ( USF ) in the adenovirus major late promoter .

The <dna>HIV-TF1-binding site</dna> in <dna>HIV LTR</dna> was similar to the site recognized by <protein>upstream stimulatory factor</protein> ( <protein>USF</protein> ) in the <dna>adenovirus major late promoter</dna> .


DNA-binding properties of HIV-TF1 suggested that HIV-TF1 might be identical or related to USF .

DNA-binding properties of <protein>HIV-TF1</protein> suggested that <protein>HIV-TF1</protein> might be identical or related to <protein>USF</protein> .


Interestingly , treatment of purified HIV-TF1 by phosphatase greatly reduced its DNA-binding activity , suggesting that phosphorylation of HIV-TF1 was essential for DNA binding .

Interestingly , treatment of purified <protein>HIV-TF1</protein> by <protein>phosphatase</protein> greatly reduced its DNA-binding activity , suggesting that phosphorylation of <protein>HIV-TF1</protein> was essential for DNA binding .


The disruption of HIV-TF1-binding site induced a 60 % decrease in the level of transcription from the HIV promoter in vivo .

The disruption of <dna>HIV-TF1-binding site</dna> induced a 60 % decrease in the level of transcription from the <dna>HIV promoter</dna> in vivo .


These results suggest that HIV-TF1 is involved in transcriptional regulation of HIV-1 .

These results suggest that <protein>HIV-TF1</protein> is involved in transcriptional regulation of HIV-1 .


Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency .

Severe 5-fluorouracil toxicity secondary to <protein>dihydropyrimidine dehydrogenase</protein> deficiency .


A potentially more common pharmacogenetic syndrome .


This study describes the inheritance of a defect in pyrimidine catabolism and its association with drug-induced toxicity in a patient receiving 5-fluorouracil ( FUra ) as adjuvant chemotherapy for breast carcinoma .


The study population included the affected patient ( proband ) , nine of her blood relatives , and seven healthy volunteers .


The activity of dihydropyrimidine dehydrogenase ( DPD ) , the initial enzyme of pyrimidine ( and FUra ) catabolism , in peripheral blood mononuclear cells was measured in each subject by a specific radiometric assay using FUra as the substrate .

The activity of <protein>dihydropyrimidine dehydrogenase</protein> ( <protein>DPD</protein> ) , the initial <protein>enzyme</protein> of pyrimidine ( and FUra ) catabolism , in <cell_type>peripheral blood mononuclear cells</cell_type> was measured in each subject by a specific radiometric assay using FUra as the substrate .


The proband had no detectable DPD activity .

The proband had no detectable <protein>DPD</protein> activity .


When enzyme levels in the proband and relatives were compared with that in controls , an autosomal recessive pattern of inheritance was demonstrated .


This is the third patient with severe FUra toxicity secondary to an alteration in pyrimidine catabolism and the second from our clinic population suggesting that the frequency of this genetic defect may be greater than previously thought .


Monitoring DPD activity may be important in the management of patients experiencing severe toxicity secondary to FUra chemotherapy .

Monitoring <protein>DPD</protein> activity may be important in the management of patients experiencing severe toxicity secondary to FUra chemotherapy .


Transactivation of the human immunodeficiency virus promoter by human herpesvirus 6 ( HHV-6 ) strains GS and Z-29 in primary human T lymphocytes and identification of transactivating HHV-6 ( GS ) gene fragments .

Transactivation of the <dna>human immunodeficiency virus promoter</dna> by human herpesvirus 6 ( HHV-6 ) strains GS and Z-29 in <cell_type>primary human T lymphocytes</cell_type> and identification of <dna>transactivating HHV-6 ( GS ) gene fragments</dna> .


Human herpesvirus 6 ( HHV-6 ) can activate the human immunodeficiency virus ( HIV ) promoter and accelerate cytopathic effects in HIV-infected human T cells .

Human herpesvirus 6 ( HHV-6 ) can activate the <dna>human immunodeficiency virus ( HIV ) promoter</dna> and accelerate cytopathic effects in <cell_type>HIV-infected human T cells</cell_type> .


This study examines the regions of the HIV promoter required for HHV-6 transactivation in a heterogeneous population of primary human T lymphocytes with or without antigenic stimulation .

This study examines the regions of the <dna>HIV promoter</dna> required for HHV-6 transactivation in a heterogeneous population of <cell_type>primary human T lymphocytes</cell_type> with or without antigenic stimulation .


Two different strains of HHV-6 , GS and Z29 , transactivated the HIV promoter .

Two different strains of HHV-6 , GS and Z29 , transactivated the <dna>HIV promoter</dna> .


The GS strain transactivated the promoter in both stimulated and resting T cells , while the Z29 strain increased HIV promoter activity only in stimulated T cells .

The GS strain transactivated the <dna>promoter</dna> in both stimulated and resting <cell_type>T cells</cell_type> , while the Z29 strain increased <dna>HIV promoter</dna> activity only in <cell_type>stimulated T cells</cell_type> .


Three DNA clones containing HHV-6 ( GS ) genomic fragments transactivated the HIV promoter in cotransfected T cells .

Three DNA clones containing <dna>HHV-6 ( GS ) genomic fragments</dna> transactivated the <dna>HIV promoter</dna> in <cell_line>cotransfected T cells</cell_line> .


A 21.4-kb DNA clone , pZVB70 , showed the highest transactivating ability , while two other DNA fragments , pZVB10 ( 6.2 kb ) and pZVH14 ( 8.7 kb ) , showed lower activity .

A <dna>21.4-kb DNA clone</dna> , <dna>pZVB70</dna> , showed the highest transactivating ability , while two other <dna>DNA fragments</dna> , <dna>pZVB10</dna> ( 6.2 kb ) and <dna>pZVH14</dna> ( 8.7 kb ) , showed lower activity .


One of these clones , pZVH14 , activated the HIV promoter construct containing a mutation in the NF kappa B site .

One of these clones , <dna>pZVH14</dna> , activated the <dna>HIV promoter construct</dna> containing a mutation in the <dna>NF kappa B site</dna> .


However , this mutated NF kappa B promoter was not transactivated during HHV-6 ( GS ) infection or after cotransfection with pZVB70 or pZVB10 .

However , this <dna>mutated NF kappa B promoter</dna> was not transactivated during HHV-6 ( GS ) infection or after cotransfection with <dna>pZVB70</dna> or <dna>pZVB10</dna> .


These data indicate that the NF kappa B sites of the HIV promoter are essential for its transactivation during HHV-6 ( GS ) infection .

These data indicate that the <dna>NF kappa B sites</dna> of the <dna>HIV promoter</dna> are essential for its transactivation during HHV-6 ( GS ) infection .


By increasing HIV promoter activity in primary T lymphocytes , HHV-6 may consequently increase HIV replication , leading to an increase in the cytopathic effect on coinfected human T cells .

By increasing <dna>HIV promoter</dna> activity in <cell_type>primary T lymphocytes</cell_type> , HHV-6 may consequently increase HIV replication , leading to an increase in the cytopathic effect on <cell_type>coinfected human T cells</cell_type> .


Inhibition of HIV-1 replication and NF-kappa B activity by cysteine and cysteine derivatives .

Inhibition of HIV-1 replication and <protein>NF-kappa B</protein> activity by cysteine and cysteine derivatives .


HIV-1 proviral DNA contains two binding sites for the transcription factor NF-kappa B .

<dna>HIV-1 proviral DNA</dna> contains two <dna>binding sites</dna> for the <protein>transcription factor</protein> <protein>NF-kappa B</protein> .


HIV-1-infected individuals have , on average , abnormally high levels of tumour necrosis factor alpha ( TNF alpha ) and abnormally low plasma cysteine levels .

HIV-1-infected individuals have , on average , abnormally high levels of <protein>tumour necrosis factor alpha</protein> ( <protein>TNF alpha</protein> ) and abnormally low plasma cysteine levels .


We therefore investigated the effects of cysteine and related thiols on HIV-1 replication and NF-kappa B expression .

We therefore investigated the effects of cysteine and related thiols on HIV-1 replication and <protein>NF-kappa B</protein> expression .


The experiments in this report show that cysteine or N-acetylcysteine ( NAC ) raise the intracellular glutathione ( GSH ) level and inhibit HIV-1 replication in persistently infected Molt-4 and U937 cells .

The experiments in this report show that cysteine or N-acetylcysteine ( NAC ) raise the intracellular glutathione ( GSH ) level and inhibit HIV-1 replication in persistently infected <cell_line>Molt-4</cell_line> and <cell_line>U937 cells</cell_line> .


However , inhibition of HIV-1 replication appears not to be directly correlated with GSH levels .


Cysteine and NAC also inhibit NF-kappa B activity as determined by electrophoretic mobility shift assays and chloramphenicol acetyl-transferase ( CAT ) gene expression under control of NF-kappa B binding sites in uninfected cells .

Cysteine and NAC also inhibit <protein>NF-kappa B</protein> activity as determined by electrophoretic mobility shift assays and <protein>chloramphenicol acetyl-transferase</protein> ( <protein>CAT</protein> ) gene expression under control of <protein>NF-kappa B</protein> <dna>binding sites</dna> in <cell_type>uninfected cells</cell_type> .


This suggests that the cysteine deficiency in HIV-1-infected individuals may cause an over-expression of NF-kappa B-dependent genes and enhance HIV-1 replication .

This suggests that the cysteine deficiency in HIV-1-infected individuals may cause an over-expression of <dna>NF-kappa B-dependent genes</dna> and enhance HIV-1 replication .


NAC may be considered for the treatment of HIV-1-infected individuals .


A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer .

A <protein>thymus-specific member</protein> of the <protein>HMG protein family</protein> regulates the <dna>human T cell receptor C alpha enhancer</dna> .


The human T cell-specific transcription factor TCF-1 alpha plays a key role in the tissue-specific activation of the T cell receptor ( TCR ) C alpha enhancer and binds to pyrimidine-rich elements ( 5'-PyCTTTG-3 ' ) present in a variety of other T cell-specific control regions .

The <protein>human T cell-specific transcription factor</protein> <protein>TCF-1 alpha</protein> plays a key role in the tissue-specific activation of the <protein>T cell receptor</protein> ( <protein>TCR</protein> ) C alpha enhancer and binds to <dna>pyrimidine-rich elements</dna> ( 5'-PyCTTTG-3 ' ) present in a variety of other <dna>T cell-specific control regions</dna> .


Using amino acid sequence information derived from the DNA affinity-purified protein , we have now isolated cDNA clones encoding TCF-1 alpha .

Using amino acid sequence information derived from the <protein>DNA affinity-purified protein</protein> , we have now isolated <dna>cDNA clones</dna> encoding <protein>TCF-1 alpha</protein> .


The TCF-1 alpha cDNA contains a single 68-amino-acid domain that is homologous to a region conserved among high-mobility group ( HMG ) and nonhistone chromosomal proteins .

The <dna>TCF-1 alpha cDNA</dna> contains a single <protein>68-amino-acid domain</protein> that is homologous to a region conserved among <protein>high-mobility group</protein> ( <protein>HMG</protein> ) and <protein>nonhistone chromosomal proteins</protein> .


Expression of full-length and mutant cDNA clones in bacteria reveal that the single HMG motif , which is predicted to contain two extended alpha-helical segments , is sufficient to direct the sequence-specific binding of TCF-1 alpha to DNA .

Expression of <dna>full-length</dna> and <dna>mutant cDNA clones</dna> in bacteria reveal that the <protein>single HMG motif</protein> , which is predicted to contain two extended <protein>alpha-helical segments</protein> , is sufficient to direct the sequence-specific binding of <protein>TCF-1 alpha</protein> to DNA .


Northern blot experiments demonstrate further that TCF-1 alpha mRNA is highly tissue specific , found primarily in the thymus or T cell lines .

Northern blot experiments demonstrate further that <rna>TCF-1 alpha mRNA</rna> is highly tissue specific , found primarily in the <cell_line>thymus or T cell lines</cell_line> .


The immature CEM T cell line expresses relatively low levels of TCF-1 alpha mRNA , which are increased upon activation of these cells by phorbol esters .

The <cell_line>immature CEM T cell line</cell_line> expresses relatively low levels of <rna>TCF-1 alpha mRNA</rna> , which are increased upon activation of these cells by phorbol esters .


Interestingly , the cloned TCF-1 alpha protein is a potent transcriptional activator of the human TCR alpha enhancer in nonlymphoid cell lines , whereas the activity of the endogenous protein in T cell lines is strongly dependent on an additional T cell-specific protein that interacts with the core enhancer .

Interestingly , the cloned <protein>TCF-1 alpha protein</protein> is a potent <protein>transcriptional activator</protein> of the <dna>human TCR alpha enhancer</dna> in <cell_line>nonlymphoid cell lines</cell_line> , whereas the activity of the <protein>endogenous protein</protein> in <cell_line>T cell lines</cell_line> is strongly dependent on an additional <cell_line>T cell-specific protein</cell_line> that interacts with the core enhancer .


TCF-1 alpha is currently unique among the newly emerging family of DNA-binding regulatory proteins that share the HMG motif in that it is a highly tissue-specific RNA polymerase II transcription factor .

<protein>TCF-1 alpha</protein> is currently unique among the newly emerging family of <protein>DNA-binding regulatory proteins</protein> that share the <protein>HMG motif</protein> in that it is a <protein>highly tissue-specific RNA polymerase II</protein> <protein>transcription factor</protein> .


A novel HIV-1 isolate containing alterations affecting the NF-kappa B element .

A novel HIV-1 isolate containing alterations affecting the <dna>NF-kappa B element</dna> .


Three molecular clones of HIV-1 , derived from a single isolate ( AL1 ) , exhibited distinct replicative and cytopathic properties during propagation in a human T cell line .

Three molecular clones of HIV-1 , derived from a single isolate ( AL1 ) , exhibited distinct replicative and cytopathic properties during propagation in a <cell_line>human T cell line</cell_line> .


The phenotypic differences observed were attributable , in large part , to changes affecting the viral LTR .

The phenotypic differences observed were attributable , in large part , to changes affecting the <dna>viral LTR</dna> .


Nucleotide sequence and PCR analyses demonstrated the presence of novel duplications or deletions involving the NF-kappa B motif .

Nucleotide sequence and PCR analyses demonstrated the presence of novel duplications or deletions involving the <dna>NF-kappa B motif</dna> .


These changes in the enhancer element were identified in the original AL1 virus stock .

These changes in the <dna>enhancer element</dna> were identified in the original AL1 virus stock .


Subcloning of the variant NF-kappa B segments into LTR-driven CAT expression vectors confirmed a correlation between promoter activity and replicative/cytopathic capacity .

Subcloning of the <dna>variant NF-kappa B segments</dna> into <dna>LTR-driven CAT expression vectors</dna> confirmed a correlation between promoter activity and replicative/cytopathic capacity .


Multiple Oct2 isoforms are generated by alternative splicing .

Multiple <protein>Oct2 isoforms</protein> are generated by alternative splicing .


The interaction of the Oct2 transcription factor with the cognate octamer motif ATGCAAAT is a critical determinant of the lymphoid-specific expression of immunoglobulin genes .

The interaction of the <protein>Oct2 transcription factor</protein> with the <dna>cognate octamer motif</dna> ATGCAAAT is a critical determinant of the lymphoid-specific expression of <dna>immunoglobulin genes</dna> .


Ectopic expression of cloned Oct2 cDNA was shown to be sufficient to reconstitute at least some aspects of this regulation in non-lymphoid cells .

Ectopic expression of <dna>cloned Oct2 cDNA</dna> was shown to be sufficient to reconstitute at least some aspects of this regulation in <cell_type>non-lymphoid cells</cell_type> .


We describe the isolation and characterization of multiple cDNAs encoding mouse Oct2 from a mature B-cell line and we show that a variety of isoforms of this transcription factor is generated from a single gene by an alternative splicing mechanism .

We describe the isolation and characterization of <dna>multiple cDNAs</dna> encoding <protein>mouse Oct2</protein> from a <cell_line>mature B-cell line</cell_line> and we show that a variety of isoforms of this <protein>transcription factor</protein> is generated from a single gene by an alternative splicing mechanism .


All the isoforms retain the previously characterized POU-domain and are therefore able to bind to the octamer motif .

All the <protein>isoforms</protein> retain the previously characterized POU-domain and are therefore able to bind to the <dna>octamer motif</dna> .


Different amounts of the various isoforms are present within the same B-cell regardless of the developmental stage of B-cell differentiation and at least some of the isoforms are conserved between mouse and humans .

Different amounts of the various <protein>isoforms</protein> are present within the same <cell_type>B-cell</cell_type> regardless of the developmental stage of <cell_type>B-cell</cell_type> differentiation and at least some of the <protein>isoforms</protein> are conserved between mouse and humans .


In cotransfection experiments we show that all the isoforms are able to activate an octamer containing promoter element in fibroblasts revealing an unexpected functional redundancy .

In cotransfection experiments we show that all the <protein>isoforms</protein> are able to activate an <dna>octamer</dna> containing <dna>promoter element</dna> in fibroblasts revealing an unexpected functional redundancy .


Finally , we show that one of the isoforms encodes the previously described lymphoid-specific Oct2B protein which has been suggested to be involved in the function of the octamer motif in the context of the immunoglobulin heavy-chain ( IgH ) enhancer .

Finally , we show that one of the <protein>isoforms</protein> encodes the previously described <protein>lymphoid-specific Oct2B protein</protein> which has been suggested to be involved in the function of the <dna>octamer motif</dna> in the context of the <dna>immunoglobulin heavy-chain ( IgH ) enhancer</dna> .


[ Regulation of intracellular cholesterol synthesis in hypercholesterolemia by glucocorticoids ]


The rate of endogenous cholesterol synthesis in blood lymphocytes and skin fibroblasts from patients with type IIa hyperlipidemia was found to be increased in comparison with healthy donors .

The rate of endogenous cholesterol synthesis in <cell_type>blood lymphocytes</cell_type> and <cell_type>skin fibroblasts</cell_type> from patients with type IIa hyperlipidemia was found to be increased in comparison with healthy donors .


The cells of hyperlipidemic patients had lowered levels of glucocorticoid receptors concomitantly with a partial loss of their sensitivity to glucocorticoids .

The cells of hyperlipidemic patients had lowered levels of <protein>glucocorticoid receptors</protein> concomitantly with a partial loss of their sensitivity to glucocorticoids .


In fibroblasts from patients with hereditary hypercholesteremia of homozygous type the number of glucocorticoid receptors did not exceed 10 % of their content in normal cells .

In <cell_type>fibroblasts</cell_type> from patients with hereditary hypercholesteremia of homozygous type the number of <protein>glucocorticoid receptors</protein> did not exceed 10 % of their content in <cell_type>normal cells</cell_type> .


The decrease of the number of glucocorticoid receptors in patients with type IIa hyperlipidemia seems to be a compensatory response of cells culminating in activation of endogenous cholesterol synthesis .

The decrease of the number of <protein>glucocorticoid receptors</protein> in patients with type IIa hyperlipidemia seems to be a compensatory response of cells culminating in activation of endogenous cholesterol synthesis .


Negative regulation of human immunodeficiency virus type 1 expression in monocytes : role of the 65-kDa plus 50-kDa NF-kappa B dimer .

Negative regulation of human immunodeficiency virus type 1 expression in monocytes : role of the <protein>65-kDa</protein> plus <protein>50-kDa NF-kappa B dimer</protein> .


Although monocytic cells can provide a reservoir for viral production in vivo , their regulation of human immunodeficiency virus type 1 ( HIV-1 ) transcription can be either latent , restricted , or productive .


These differences in gene expression have not been molecularly defined .


In THP-1 cells with restricted HIV expression , there is an absence of DNA-protein binding complex formation with the HIV-1 promoter-enhancer associated with markedly less viral RNA production .

In <cell_line>THP-1 cells</cell_line> with restricted HIV expression , there is an absence of <protein>DNA-protein binding complex</protein> formation with the <dna>HIV-1 promoter-enhancer</dna> associated with markedly less <rna>viral RNA</rna> production .


This absence of binding was localized to the NF-kappa B region of the HIV-1 enhancer ; the 65-kDa plus 50-kDa NF-kappa B heterodimer was preferentially lost .

This absence of binding was localized to the <dna>NF-kappa B region</dna> of the <dna>HIV-1 enhancer</dna> ; the <protein>65-kDa plus 50-kDa NF-kappa B heterodimer</protein> was preferentially lost .


Adding purified NF-kappa B protein to nuclear extracts from cells with restricted expression overcomes this lack of binding .

Adding purified <protein>NF-kappa B protein</protein> to nuclear extracts from cells with restricted expression overcomes this lack of binding .


In addition , treatment of these nuclear extracts with sodium deoxycholate restored their ability to form the heterodimer , suggesting the presence of an inhibitor of NF-kappa B activity .

In addition , treatment of these nuclear extracts with sodium deoxycholate restored their ability to form the <protein>heterodimer</protein> , suggesting the presence of an inhibitor of <protein>NF-kappa B</protein> activity .


Furthermore , treatment of nuclear extracts from these cells that had restricted expression with lipopolysaccharide increased viral production and NF-kappa B activity .

Furthermore , treatment of nuclear extracts from these cells that had restricted expression with lipopolysaccharide increased viral production and <protein>NF-kappa B</protein> activity .


Antiserum specific for NF-kappa B binding proteins , but not c-rel-specific antiserum , disrupted heterodimer complex formation .

Antiserum specific for <protein>NF-kappa B binding proteins</protein> , but not c-rel-specific antiserum , disrupted <protein>heterodimer complex</protein> formation .


Thus , both NF-kappa B-binding complexes are needed for optimal viral transcription .

Thus , both <protein>NF-kappa B-binding complexes</protein> are needed for optimal viral transcription .


Binding of the 65-kDa plus 50-kDa heterodimer to the HIV-1 enhancer can be negatively regulated in monocytes , providing one mechanism restricting HIV-1 gene expression .

Binding of the <protein>65-kDa</protein> plus <protein>50-kDa heterodimer</protein> to the <dna>HIV-1 enhancer</dna> can be negatively regulated in <cell_type>monocytes</cell_type> , providing one mechanism restricting <dna>HIV-1 gene</dna> expression .


Glucocorticoid receptors in normal leukocytes : effects of age , gender , season , and plasma cortisol concentrations .

<protein>Glucocorticoid receptors</protein> in <cell_type>normal leukocytes</cell_type> : effects of age , gender , season , and plasma cortisol concentrations .


We measured glucocorticoid receptors ( GR ) in mononuclear leukocytes ( MNL ) isolated from peripheral blood of 145 apparently healthy volunteers ( 86 men and 59 women ) .

We measured <protein>glucocorticoid receptors</protein> ( <protein>GR</protein> ) in <cell_type>mononuclear leukocytes</cell_type> ( <cell_type>MNL</cell_type> ) isolated from peripheral blood of 145 apparently healthy volunteers ( 86 men and 59 women ) .


An age-related decrease in the number of GR was suggested between subjects younger than 20 years and elderly subjects ; there was no apparent seasonal variation in GR .

An age-related decrease in the number of <protein>GR</protein> was suggested between subjects younger than 20 years and elderly subjects ; there was no apparent seasonal variation in <protein>GR</protein> .


Gender difference in the number of GR was not significant , although women showed slightly fewer GR .

Gender difference in the number of <protein>GR</protein> was not significant , although women showed slightly fewer <protein>GR</protein> .


Eight patients with dermatomyositis/polymyositis were examined to determine whether the number of GR in MNL could be down-regulated by their cognate ligands .

Eight patients with dermatomyositis/polymyositis were examined to determine whether the number of <protein>GR</protein> in <cell_type>MNL</cell_type> could be down-regulated by their cognate ligands .


The number of GR in MNL from these patients was significantly decreased one month after the initiation of prednisolone therapy .

The number of <protein>GR</protein> in <cell_type>MNL</cell_type> from these patients was significantly decreased one month after the initiation of prednisolone therapy .


However , in normal subjects , the GR in MNL did not demonstrate circadian variation , in contrast to concentrations of plasma cortisol .

However , in normal subjects , the <protein>GR</protein> in <cell_type>MNL</cell_type> did not demonstrate circadian variation , in contrast to concentrations of plasma cortisol .


Synergism between two distinct elements of the HTLV-I enhancer during activation by the trans-activator of HTLV-I .

Synergism between two distinct elements of the <dna>HTLV-I enhancer</dna> during activation by the <protein>trans-activator</protein> of HTLV-I .


We have conducted functional studies of the enhancer elements of human T-cell leukemia virus type I ( HTLV-I ) using the human T-cell lines Jurkat and MOLT 4 , which are negative for HTLV-I , and MT-2 and TL-Mor , which carry the proviral genome of HTLV-I .

We have conducted functional studies of the <dna>enhancer elements</dna> of human T-cell leukemia virus type I ( HTLV-I ) using the <cell_line>human T-cell lines</cell_line> <cell_line>Jurkat</cell_line> and <cell_line>MOLT 4</cell_line> , which are negative for HTLV-I , and MT-2 and TL-Mor , which carry the proviral genome of HTLV-I .


Two distinct elements have been implicated in function of the HTLV-I enhancer .

Two distinct elements have been implicated in function of the <dna>HTLV-I enhancer</dna> .


One is the 21-base-pair ( bp ) core element that is responsible for trans-activation by the HTLV-I trans-activator p40tax and that has the ability to bind to cyclic-AMP responsive element binding factor ( CREB ) -like factor ( s ) .

One is the <dna>21-base-pair ( bp ) core element</dna> that is responsible for trans-activation by the HTLV-I <protein>trans-activator</protein> <protein>p40tax</protein> and that has the ability to bind to <protein>cyclic-AMP responsive element binding factor ( CREB ) -like factor</protein> ( s ) .


The other is a region interposed between the 21-bp elements .

The other is a region interposed between the <dna>21-bp elements</dna> .


In this study we demonstrate that a subfragment ( C26 ) in the region between the 21-bp elements is involved in trans-activation by p40tax , possibly through binding to an NF-kappa B-like nuclear factor or factors .

In this study we demonstrate that a subfragment ( C26 ) in the region between the <dna>21-bp elements</dna> is involved in trans-activation by <protein>p40tax</protein> , possibly through binding to an <protein>NF-kappa B-like nuclear factor</protein> or factors .


Formation of the protein-DNA complex with the C26 subfragment was positively affected by p40tax .

Formation of the <protein>protein-DNA complex</protein> with the <protein>C26 subfragment</protein> was positively affected by <protein>p40tax</protein> .


The C26 element conferred partial responsiveness to p40tax when linked to one copy of the 21-bp element that , by itself , showed little activation in response to p40tax .

The <dna>C26 element</dna> conferred partial responsiveness to <protein>p40tax</protein> when linked to one copy of the <dna>21-bp element</dna> that , by itself , showed little activation in response to <protein>p40tax</protein> .


However , the C26 element alone , even when repeated , could not be activated by p40tax , unlike other NF-kappa B-binding elements .

However , the <dna>C26 element</dna> alone , even when repeated , could not be activated by <protein>p40tax</protein> , unlike other <dna>NF-kappa B-binding elements</dna> .


In contrast , the C26 element itself was profoundly activated upon stimulation with 12-O-tetradecanoylphorbol-13-acetate .

In contrast , the <dna>C26 element</dna> itself was profoundly activated upon stimulation with 12-O-tetradecanoylphorbol-13-acetate .


These findings therefore suggest that the HTLV-I enhancer contains multiple functional elements , including binding sites for at least CREB- and NF-kappa B-like factors , which synergistically cooperate in activation of the HTLV-I enhancer in response to p40tax .

These findings therefore suggest that the <dna>HTLV-I enhancer</dna> contains <dna>multiple functional elements</dna> , including binding sites for at least <protein>CREB- and NF-kappa B-like factors</protein> , which synergistically cooperate in activation of the <dna>HTLV-I enhancer</dna> in response to <protein>p40tax</protein> .


Our results also demonstrate that TPA-dependent activation of the HTLV-I enhancer may be mediated through the C26 element .

Our results also demonstrate that TPA-dependent activation of the <dna>HTLV-I enhancer</dna> may be mediated through the <dna>C26 element</dna> .


Human tumor necrosis factor alpha gene regulation in phorbol ester stimulated T and B cell lines .

Human <protein>tumor necrosis factor alpha</protein> gene regulation in phorbol ester <cell_line>stimulated T and B cell lines</cell_line> .


The minimal region of the human tumor necrosis factor alpha ( TNF-alpha ) gene promoter necessary for its transcriptional induction by phorbol esters ( PMA ) in human T and B lymphocyte cell lines has been localized between -52 and +89 nucleotides ( nt ) relative to the gene 's transcriptional start site .

The minimal region of the <dna>human tumor necrosis factor alpha ( TNF-alpha ) gene promoter</dna> necessary for its transcriptional induction by phorbol esters ( PMA ) in <cell_line>human T and B lymphocyte cell lines</cell_line> has been localized between <dna>-52 and +89 nucleotides</dna> ( nt ) relative to the gene 's <dna>transcriptional start site</dna> .


Comparison of these sequences to those required to mediate virus or lipopolysaccharide ( LPS ) induction of the gene reveal significant differences , and thus , the sequence requirements for PMA induction are distinct from those that mediate induction by virus or LPS .


Although three sites in the TNF-alpha promoter ( kappa 1 , kappa 2 , and kappa 3 ) specifically bind the transcription factor NF-kappa B in lymphoid nuclear extracts , TNF-alpha mRNA induction by PMA does not correlate with NF-kappa B binding activities displayed by different T and B cell lines .

Although three sites in the <dna>TNF-alpha promoter</dna> ( kappa 1 , kappa 2 , and kappa 3 ) specifically bind the <protein>transcription factor</protein> <protein>NF-kappa B</protein> in lymphoid nuclear extracts , <rna>TNF-alpha mRNA</rna> induction by PMA does not correlate with <protein>NF-kappa B</protein> binding activities displayed by different <cell_line>T and B cell lines</cell_line> .


Moreover , kappa 1-kappa 3 can each be deleted from the TNF-alpha promoter with little effect on the gene 's inducibility by PMA .

Moreover , <dna>kappa 1-kappa 3</dna> can each be deleted from the <dna>TNF-alpha promoter</dna> with little effect on the gene 's inducibility by PMA .


Therefore , TNF-alpha mRNA induction by PMA , like its induction by virus and LPS , is not primarily mediated by NF-kappa B , but rather is mediated through other sequences and protein factors .

Therefore , <rna>TNF-alpha mRNA</rna> induction by PMA , like its induction by virus and LPS , is not primarily mediated by <protein>NF-kappa B</protein> , but rather is mediated through other sequences and <protein>protein factors</protein> .


Surprisingly , multimers of kappa 1-kappa 3 can confer PMA inducibility on a heterologous promoter in a B ( Raji ) , but not a T ( HUT78 ) cell line .

Surprisingly , multimers of kappa 1-kappa 3 can confer PMA inducibility on a <dna>heterologous promoter</dna> in a <cell_line>B ( Raji ) , but not a T ( HUT78 ) cell line</cell_line> .


However they are not functional on a truncated TNF-alpha promoter , indicating that promoter context and cell type specificity influence the PMA inducible function of these NF-kappa B binding sites .

However they are not functional on a truncated <dna>TNF-alpha promoter</dna> , indicating that promoter context and cell type specificity influence the PMA inducible function of these <dna>NF-kappa B binding sites</dna> .


Differentiation-associated expression of the Epstein-Barr virus BZLF1 transactivator protein in oral hairy leukoplakia .

Differentiation-associated expression of the <protein>Epstein-Barr virus BZLF1 transactivator protein</protein> in oral hairy leukoplakia .


The BZLF1 protein of Epstein-Barr virus ( EBV ) is a key immediate-early protein which has been shown to disrupt virus latency in EBV-infected B cells .

The <protein>BZLF1 protein</protein> of Epstein-Barr virus ( EBV ) is a key <protein>immediate-early protein</protein> which has been shown to disrupt virus latency in <cell_type>EBV-infected B cells</cell_type> .


We have generated a monoclonal antibody , BZ1 , to BZLF1 which reacts in immunohistology , immunoblotting , and immunoprecipitation and which recognizes both the active , dimeric form and the inactive , monomeric form of the protein .

We have generated a <protein>monoclonal antibody</protein> , <protein>BZ1</protein> , to <protein>BZLF1</protein> which reacts in immunohistology , immunoblotting , and immunoprecipitation and which recognizes both the <protein>active , dimeric form</protein> and the <protein>inactive , monomeric form</protein> of the protein .


Biopsies of oral hairy leukoplakia , an AIDS-associated lesion characterized by high-level EBV replication , were examined by immunohistochemistry using the BZ1 monoclonal antibody .

Biopsies of oral hairy leukoplakia , an AIDS-associated lesion characterized by high-level EBV replication , were examined by immunohistochemistry using the <protein>BZ1</protein> <protein>monoclonal antibody</protein> .


A differentiation-associated pattern of BZLF1 expression was observed , BZ1 reacting with nuclei of the upper spinous layer of the lesion .

A differentiation-associated pattern of <protein>BZLF1</protein> expression was observed , <protein>BZ1</protein> reacting with nuclei of the upper spinous layer of the lesion .


This finding suggests that the BZLF1 promoter may be regulated by the degree of squamous differentiation .

This finding suggests that the <dna>BZLF1 promoter</dna> may be regulated by the degree of squamous differentiation .


A comparison of in situ hybridization to EBV DNA and viral capsid antigen staining with BZ1 reactivity suggested that BZLF1 expression precedes rampant virus replication .

A comparison of in situ hybridization to <dna>EBV DNA</dna> and <protein>viral capsid antigen</protein> staining with <protein>BZ1</protein> reactivity suggested that <protein>BZLF1</protein> expression precedes rampant virus replication .


The inability to detect EBV in the lower epithelial layers of oral hairy leukoplakia raises questions concerning the nature of EBV latency and persistence in stratified squamous epithelium .


[ Changes in levels of leucocytic estrogen receptor in patients with menopausal type II diabetes and its significance ]

[ Changes in levels of <protein>leucocytic estrogen receptor</protein> in patients with menopausal type II diabetes and its significance ]


The number of estrogen receptors ( ER ) in human peripheral leucocytes in 12 women with menopausal type II diabetes was measured with radio-ligand binding method .

The number of <protein>estrogen receptors</protein> ( <protein>ER</protein> ) in <cell_type>human peripheral leucocytes</cell_type> in 12 women with menopausal type II diabetes was measured with radio-ligand binding method .


The results were compared with those of 12 menopausal women without diabetes and 12 normal women of childbearing age .


It was found that the number of ER in the patients was significantly decreased .

It was found that the number of <protein>ER</protein> in the patients was significantly decreased .


Our data indicate that decrease of ER level in leukocytes may be related to the pathogenesis of type II diabetes in menopausal period .

Our data indicate that decrease of <protein>ER</protein> level in <cell_type>leukocytes</cell_type> may be related to the pathogenesis of type II diabetes in menopausal period .


Lymphocyte glucocorticoid receptor number in posttraumatic stress disorder .

Lymphocyte <protein>glucocorticoid receptor</protein> number in posttraumatic stress disorder .


OBJECTIVE : The authors ' objective was to investigate the possibility that glucocorticoid receptor changes may be involved in the dysregulation of the hypothalamic-pituitary-adrenal ( HPA ) axis in posttraumatic stress disorder ( PTSD ) .

OBJECTIVE : The authors ' objective was to investigate the possibility that <protein>glucocorticoid receptor</protein> changes may be involved in the dysregulation of the hypothalamic-pituitary-adrenal ( HPA ) axis in posttraumatic stress disorder ( PTSD ) .


METHOD : They measured the number of lymphocyte cytosolic glucocorticoid receptors and plasma cortisol concentrations in 15 consecutively admitted male combat Vietnam veterans with PTSD and in a normal comparison group of 11 subjects .

METHOD : They measured the number of <protein>lymphocyte cytosolic glucocorticoid receptors</protein> and plasma cortisol concentrations in 15 consecutively admitted male combat Vietnam veterans with PTSD and in a normal comparison group of 11 subjects .


RESULTS : Both the patients and the normal comparison subjects showed a morning-to-afternoon decline in glucocorticoid receptor concentrations , paralleling the normal diurnal decline in cortisol levels .

RESULTS : Both the patients and the normal comparison subjects showed a morning-to-afternoon decline in <protein>glucocorticoid receptor</protein> concentrations , paralleling the normal diurnal decline in cortisol levels .


The number of glucocorticoid receptors was 63 % greater in the morning and 26 % greater in the afternoon in the patients with PTSD than in the normal subjects .

The number of <protein>glucocorticoid receptors</protein> was 63 % greater in the morning and 26 % greater in the afternoon in the patients with PTSD than in the normal subjects .


No group differences in cortisol levels were observed , nor were glucocorticoid receptor number and cortisol levels correlated .

No group differences in cortisol levels were observed , nor were <protein>glucocorticoid receptor</protein> number and cortisol levels correlated .


The number of morning glucocorticoid receptors was positively correlated with symptoms of PTSD and anxiety .

The number of <protein>morning glucocorticoid receptors</protein> was positively correlated with symptoms of PTSD and anxiety .


CONCLUSIONS : These results provide further evidence for a dysregulation of the HPA axis in PTSD .


The finding that patients with PTSD had a substantially greater number of lymphocyte glucocorticoid receptors than normal comparison subjects is consistent with the authors ' previous observations of low 24-hour urinary cortisol excretion in subjects with PTSD .

The finding that patients with PTSD had a substantially greater number of <protein>lymphocyte glucocorticoid receptors</protein> than normal comparison subjects is consistent with the authors ' previous observations of low 24-hour urinary cortisol excretion in subjects with PTSD .


Furthermore , the receptor changes observed are opposite of those reported in major depressive disorder .


The present data , along with other findings of HPA abnormalities in PTSD , support the possibility of a greater negative feedback sensitivity at one or more levels of the HPA axis .


Induction of NF-kappa B during monocyte differentiation is associated with activation of HIV-gene expression .

Induction of <protein>NF-kappa B</protein> during monocyte differentiation is associated with activation of HIV-gene expression .


Cells of the monocyte-macrophage lineage are important targets of HIV infection .

Cells of the <cell_type>monocyte-macrophage lineage</cell_type> are important targets of HIV infection .


We report here that the phenotypic differentiation of monocyte cell lines induced by phorbol esters or tumour necrosis factor alpha ( TNF alpha ) is associated with expression of nuclear factor kappa B ( NF-kappa B ) .

We report here that the phenotypic differentiation of <cell_line>monocyte cell lines</cell_line> induced by phorbol esters or <protein>tumour necrosis factor alpha</protein> ( <protein>TNF alpha</protein> ) is associated with expression of <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) .


In parallel with such differentiation , HIV transcription , monitored using an HIV long terminal repeat reporter gene construct , is activated in such cells under the influence of enhanced NF-kappa B expression .

In parallel with such differentiation , HIV transcription , monitored using an <dna>HIV long terminal repeat reporter gene construct</dna> , is activated in such cells under the influence of enhanced <protein>NF-kappa B</protein> expression .


Also , in a promonocyte cell line chronically infected with HIV , NF-kappa B expression and HIV transcription were enhanced on stimulation with phorbol ester or TNF alpha .

Also , in a <cell_line>promonocyte cell line</cell_line> chronically infected with HIV , <protein>NF-kappa B</protein> expression and HIV transcription were enhanced on stimulation with phorbol ester or <protein>TNF alpha</protein> .


Thus , stimulation of monocyte cell lines by phorbol esters or TNF alpha induces cell differentiation and activates HIV transcription .

Thus , stimulation of <cell_line>monocyte cell lines</cell_line> by phorbol esters or <protein>TNF alpha</protein> induces cell differentiation and activates HIV transcription .


Such a process may have fundamental implications in AIDS pathogenesis in vivo and may be important in disease progression induced by opportunistic infections directly or indirectly involving macrophages .

Such a process may have fundamental implications in AIDS pathogenesis in vivo and may be important in disease progression induced by opportunistic infections directly or indirectly involving <cell_type>macrophages</cell_type> .


Demonstration of estrogen and progesterone receptors as well as Ki-67 and p-145 antigens in single tumor cells from blood and pleural effusions using a slide assay .

Demonstration of <protein>estrogen and progesterone receptors</protein> as well as <protein>Ki-67 and p-145 antigens</protein> in <cell_type>single tumor cells</cell_type> from blood and pleural effusions using a slide assay .


We describe a slide assay that allows the demonstration of antigens localized in the nucleus from isolated white blood cells as well as from single tumor cells derived from malignant effusions .

We describe a slide assay that allows the demonstration of <protein>antigens</protein> localized in the nucleus from <cell_type>isolated white blood cells</cell_type> as well as from <cell_type>single tumor cells</cell_type> derived from malignant effusions .


With the antibodies Ki-67 and anti-p-145 an increased rate of nuclear and nucleolar staining resulted in cells from highly malignant lymphomas .

With the antibodies <protein>Ki-67</protein> and <protein>anti-p-145</protein> an increased rate of nuclear and nucleolar staining resulted in cells from highly malignant lymphomas .


An almost identical reaction was obtained when tumor cells from malignant effusions were tested .

An almost identical reaction was obtained when <cell_type>tumor cells</cell_type> from malignant effusions were tested .


Cells isolated from the blood of patients with leukemic spread of lymphomas of low malignancy yielded a weak staining comparable to that of normal mesothelial cells from non-tumorous cavity fluids .

Cells isolated from the blood of patients with leukemic spread of lymphomas of low malignancy yielded a weak staining comparable to that of <cell_type>normal mesothelial cells</cell_type> from non-tumorous cavity fluids .


The detection of estrogen and progesterone receptors ( ER and PR ) localized in the cell nucleus can be achieved by the same assay .

The detection of <protein>estrogen</protein> and <protein>progesterone receptors</protein> ( <protein>ER</protein> and <protein>PR</protein> ) localized in the cell nucleus can be achieved by the same assay .


The reaction is enhanced by incubation of the tumor cells for 30 min at 37 degrees C prior to fixation .

The reaction is enhanced by incubation of the <cell_type>tumor cells</cell_type> for 30 min at 37 degrees C prior to fixation .


Pleural effusions from 20 patients with breast cancer were tested .


ER was positive in 13 and PR was positive in 12 of the 20 samples .

<protein>ER</protein> was positive in 13 and <protein>PR</protein> was positive in 12 of the 20 samples .


In 5 cases there was a divergent reaction with ER and PR antibody .

In 5 cases there was a divergent reaction with <protein>ER</protein> and <protein>PR</protein> antibody .


The hormone receptors of the primary tumor were known in 15 ( ER ) and 14 ( PR ) patients , respectively .

The <protein>hormone receptors</protein> of the primary tumor were known in 15 ( <protein>ER</protein> ) and 14 ( <protein>PR</protein> ) patients , respectively .


In each cohort there was only one case with a negative reaction of the primary tumor and a positive reaction with the isolated tumor cells from the pleural effusions .

In each cohort there was only one case with a negative reaction of the primary tumor and a positive reaction with the isolated <cell_type>tumor cells</cell_type> from the pleural effusions .


These results indicate that the demonstration of hormone receptor proteins in cells from malignant effusions is possible and that there is a correlation with the status of the primary site of cancer .

These results indicate that the demonstration of <protein>hormone receptor proteins</protein> in cells from malignant effusions is possible and that there is a correlation with the status of the primary site of cancer .


Constitutive activation of NF-kB in human thymocytes .

Constitutive activation of <protein>NF-kB</protein> in <cell_type>human thymocytes</cell_type> .


NF-kB is a eukaryotic transcription regulatory factor .

<protein>NF-kB</protein> is a <protein>eukaryotic transcription regulatory factor</protein> .


In T cells and T cell lines , NF-kB is bound to a cytoplasmic proteic inhibitor , the IkB .

In <cell_type>T cells</cell_type> and <cell_line>T cell lines</cell_line> , <protein>NF-kB</protein> is bound to a <protein>cytoplasmic proteic inhibitor</protein> , the <protein>IkB</protein> .


Treatment of T cells with mitogens ( phorbol esters ) or cytokines ( TNF alpha ) induces NF-kB nuclear translocation and the subsequent expression of NF-kB dependent T cell genes .

Treatment of <cell_type>T cells</cell_type> with mitogens ( phorbol esters ) or <protein>cytokines</protein> ( <protein>TNF alpha</protein> ) induces <protein>NF-kB</protein> nuclear translocation and the subsequent expression of <dna>NF-kB dependent T cell genes</dna> .


Here we examined the activation of NF-kB in human T cell thymic progenitors .

Here we examined the activation of <protein>NF-kB</protein> in <cell_type>human T cell thymic progenitors</cell_type> .