Activation of JAK3 , but not JAK1 , is critical for IL-2 -induced proliferation and STAT5 recruitment by a COOH-terminal region of the IL-2 receptor beta-chain .

Activation of <protein>JAK3</protein> , but not <protein>JAK1</protein> , is critical for <protein>IL-2</protein> -induced proliferation and <protein>STAT5</protein> recruitment by a <protein>COOH-terminal region</protein> of the <protein>IL-2 receptor beta-chain</protein> .


A number of cytokines and growth factors use the JAK -STAT pathway to signal from the cell membrane to the nucleus .

A number of <protein>cytokines</protein> and <protein>growth factors</protein> use the <protein>JAK</protein> <protein>-STAT</protein> pathway to signal from the cell membrane to the nucleus .


While homodimerizing cytokine receptors may transmit signal via a single form of JAK ( i.e . growth hormone receptors ) , several multicomponent cytokine receptors have been shown to require simultaneous activation of pairs of different JAK kinases ( i.e . interferon receptors ) .

While <protein>homodimerizing cytokine receptors</protein> may transmit signal via a single form of <protein>JAK</protein> ( i.e . <protein>growth hormone receptors</protein> ) , several <protein>multicomponent cytokine receptors</protein> have been shown to require simultaneous activation of pairs of different <protein>JAK kinases</protein> ( i.e . <protein>interferon receptors</protein> ) .


Recent evidence for a preferential coupling of JAK3 to interleukin-2 receptor-gamma ( IL-2R gamma ) and JAK1 to IL-2R beta supports the concept of heterotrans-activation of JAK1 and JAK3 caused by IL-2 -induced heterodimerization of their receptor partners .

Recent evidence for a preferential coupling of <protein>JAK3</protein> to <protein>interleukin-2 receptor-gamma</protein> ( <protein>IL-2R gamma</protein> ) and <protein>JAK1</protein> to <protein>IL-2R beta</protein> supports the concept of heterotrans-activation of <protein>JAK1</protein> and <protein>JAK3</protein> caused by <protein>IL-2</protein> -induced heterodimerization of their receptor partners .


The present study verified the ability of IL-2 to cause tyrosine phosphorylation and activation of JAK1 and JAK3 , but demonstrated that IL-2 stimulated JAK3 to a significantly larger extent than JAK1 in human T lymphocytes and the YT cell line .

The present study verified the ability of <protein>IL-2</protein> to cause tyrosine phosphorylation and activation of <protein>JAK1</protein> and <protein>JAK3</protein> , but demonstrated that <protein>IL-2</protein> stimulated <protein>JAK3</protein> to a significantly larger extent than <protein>JAK1</protein> in <cell_type>human T lymphocytes</cell_type> and the <cell_line>YT cell line</cell_line> .


This conclusion was based upon several independent criteria , including more vigorous tyrosine phosphorylation of JAK3 , more marked enzymatic activation of JAK3 as well as higher abundance of JAK3 in activated IL-2 receptor complexes .

This conclusion was based upon several independent criteria , including more vigorous tyrosine phosphorylation of <protein>JAK3</protein> , more marked enzymatic activation of <protein>JAK3</protein> as well as higher abundance of <protein>JAK3</protein> in activated <protein>IL-2 receptor complexes</protein> .


Furthermore , when human IL-2R beta was stably expressed in murine BA/F3 cells , robust IL-2 -induced proliferation and JAK3 activation occurred without detectable involvement of either JAK1 , JAK2 or TYK2 .

Furthermore , when <protein>human IL-2R beta</protein> was stably expressed in <cell_line>murine BA/F3 cells</cell_line> , robust <protein>IL-2</protein> -induced proliferation and <protein>JAK3</protein> activation occurred without detectable involvement of either <protein>JAK1</protein> , <protein>JAK2</protein> or <protein>TYK2</protein> .


We therefore propose that IL-2 receptor signal transduction does not depend on equimolar heterodimerization of JAK1 and JAK3 following IL-2 -induced heterodimerization of IL-2R beta and IL-2R gamma .

We therefore propose that <protein>IL-2 receptor</protein> signal transduction does not depend on equimolar heterodimerization of <protein>JAK1</protein> and <protein>JAK3</protein> following <protein>IL-2</protein> -induced heterodimerization of <protein>IL-2R beta</protein> and <protein>IL-2R gamma</protein> .


Nonetheless , a membrane-proximal region of human IL-2R beta ( Asn240-Leu335 ) was critical for JAK3 activation , and the amount of JAK3 present in activated IL-2 receptor complexes increased with time , suggesting that stabilization of JAK3 binding to the receptor complex relies on both IL-2R beta and IL-2R gamma .

Nonetheless , a <protein>membrane-proximal region</protein> of human <protein>IL-2R beta</protein> ( <protein>Asn240-Leu335</protein> ) was critical for <protein>JAK3</protein> activation , and the amount of <protein>JAK3</protein> present in activated <protein>IL-2 receptor complexes</protein> increased with time , suggesting that stabilization of <protein>JAK3</protein> binding to the <protein>receptor complex</protein> relies on both <protein>IL-2R beta</protein> and <protein>IL-2R gamma</protein> .


Moreover , STAT5 was found to be the predominant STAT transcription factor used by IL-2 in human T cells , and specifically required a COOH-terminal region of IL-2R beta ( Ser386-Val525 ) , while STAT5 recruitment was not correlated to activation of IL-2R gamma or JAK3 .

Moreover , <protein>STAT5</protein> was found to be the predominant <protein>STAT transcription factor</protein> used by <protein>IL-2</protein> in <cell_type>human T cells</cell_type> , and specifically required a <protein>COOH-terminal region</protein> of <protein>IL-2R beta</protein> ( <protein>Ser386-Val525</protein> ) , while <protein>STAT5</protein> recruitment was not correlated to activation of <protein>IL-2R gamma</protein> or <protein>JAK3</protein> .


Up-regulation of high-affinity dehydroepiandrosterone binding activity by dehydroepiandrosterone in activated human T lymphocytes .

Up-regulation of high-affinity dehydroepiandrosterone binding activity by dehydroepiandrosterone in activated <cell_type>human T lymphocytes</cell_type> .


Although evidence indicates that dehydroepiandrosterone ( DHEA ) exerts direct physiological effects , its mechanism of action remains unknown .


DHEA binding sites were examined using a whole-cell binding assay in a human T lymphoid cell line , PEER , revealing that a single class of high-affinity binding sites for DHEA ( dissociation constant = 7.4 +/- 0.53 nmol/L , mean +/- SE , n = 4 ) was greatly increased when treated with DHEA , phorbol-12-myristate-13-acetate , and the Ca2+ ionophore A23187 .

DHEA binding sites were examined using a whole-cell binding assay in a <cell_line>human T lymphoid cell line</cell_line> , <cell_line>PEER</cell_line> , revealing that a single class of high-affinity binding sites for DHEA ( dissociation constant = 7.4 +/- 0.53 nmol/L , mean +/- SE , n = 4 ) was greatly increased when treated with DHEA , phorbol-12-myristate-13-acetate , and the Ca2+ ionophore A23187 .


Bound [ 3H ] DHEA was displaced sensitively by DHEA and secondarily by dihydrotestosterone , but not effectively by other steroids , including DHEA sulfate .


These results not only indicate the existence of a DHEA receptor , but also suggest that T cells become susceptible to regulation by DHEA during the process of signal-induced activation .

These results not only indicate the existence of a <protein>DHEA receptor</protein> , but also suggest that <cell_type>T cells</cell_type> become susceptible to regulation by DHEA during the process of signal-induced activation .


Ubiquitin-mediated processing of NF-kappa B transcriptional activator precursor p105 .

Ubiquitin-mediated processing of <protein>NF-kappa B</protein> <protein>transcriptional activator precursor</protein> <protein>p105</protein> .


Reconstitution of a cell-free system and identification of the ubiquitin-carrier protein , E2 , and a novel ubiquitin-protein ligase , E3 , involved in conjugation .

Reconstitution of a cell-free system and identification of the <protein>ubiquitin-carrier protein</protein> , <protein>E2</protein> , and a novel <protein>ubiquitin-protein ligase</protein> , <protein>E3</protein> , involved in conjugation .


In most cases , the transcriptional factor NF-kappa B is a heterodimer consisting of two subunits , p50 and p65 , which are encoded by two distinct genes of the Rel family .

In most cases , the <protein>transcriptional factor</protein> <protein>NF-kappa B</protein> is a <protein>heterodimer</protein> consisting of two subunits , <protein>p50</protein> and <protein>p65</protein> , which are encoded by two distinct genes of the <dna>Rel family</dna> .


p50 is translated as a precursor of 105 kDa .

<protein>p50</protein> is translated as a precursor of <protein>105 kDa</protein> .


The C-terminal domain of the precursor is rapidly degraded , forming the mature p50 subunit consisted of the N-terminal region of the molecule .

The <protein>C-terminal domain</protein> of the precursor is rapidly degraded , forming the <protein>mature p50 subunit</protein> consisted of the <protein>N-terminal region</protein> of the molecule .


The mechanism of generation of p50 is not known .

The mechanism of generation of <protein>p50</protein> is not known .


It has been suggested that the ubiquitin -proteasome system is involved in the process ; however , the specific enzymes involved and the mechanism of limited proteolysis , in which half of the molecule is spared , have been obscure .

It has been suggested that the <protein>ubiquitin</protein> <protein>-proteasome</protein> system is involved in the process ; however , the specific <protein>enzymes</protein> involved and the mechanism of limited proteolysis , in which half of the molecule is spared , have been obscure .


Palombella and colleagues ( Palombella , V.J. , Rando , O.J. , Goldberg , A.L. , and Maniatis , T. ( 1994 ) Cell 78 , 773-785 ) have shown that ubiquitin is required for the processing in a cell-free system of a truncated , artificially constructed , 60-kDa precursor .

Palombella and colleagues ( Palombella , V.J. , Rando , O.J. , Goldberg , A.L. , and Maniatis , T. ( 1994 ) Cell 78 , 773-785 ) have shown that <protein>ubiquitin</protein> is required for the processing in a cell-free system of a truncated , artificially constructed , <protein>60-kDa precursor</protein> .


They have also shown that proteasome inhibitors block the processing both in vitro and in vivo .

They have also shown that <protein>proteasome</protein> inhibitors block the processing both in vitro and in vivo .


In this study , we demonstrate reconstitution of a cell-free processing system and demonstrate directly that : ( a ) the ubiquitin -proteasome system is involved in processing of the intact p105 precursor , ( b ) conjugation of ubiquitin to the precursor is an essential intermediate step in the processing , ( c ) the recently discovered novel species of the ubiquitin-carrier protein , E2-F1 , that is involved in the conjugation and degradation of p53 , is also required for the limited processing of the p105 precursor , and ( d ) a novel , approximately 320-kDa species of ubiquitin-protein ligase , is involved in the process .

In this study , we demonstrate reconstitution of a cell-free processing system and demonstrate directly that : ( a ) the <protein>ubiquitin</protein> <protein>-proteasome</protein> system is involved in processing of the intact <protein>p105</protein> precursor , ( b ) conjugation of <protein>ubiquitin</protein> to the precursor is an essential intermediate step in the processing , ( c ) the recently discovered novel species of the <protein>ubiquitin-carrier protein</protein> , <protein>E2-F1</protein> , that is involved in the conjugation and degradation of <protein>p53</protein> , is also required for the limited processing of the <protein>p105 precursor</protein> , and ( d ) a novel , approximately <protein>320-kDa species</protein> of <protein>ubiquitin-protein ligase</protein> , is involved in the process .


This novel enzyme is distinct from E6-AP , the p53-conjugating ligase , and from E3 alpha , the `` N-end rule '' ligase .

This novel enzyme is distinct from <protein>E6-AP</protein> , the <protein>p53-conjugating ligase</protein> , and from <protein>E3 alpha</protein> , the <protein>`` N-end rule '' ligase</protein> .


Flutamide in the treatment of hirsutism : long-term clinical effects , endocrine changes , and androgen receptor behavior .

Flutamide in the treatment of hirsutism : long-term clinical effects , endocrine changes , and <protein>androgen receptor</protein> behavior .


OBJECTIVE : To investigate the long-term effects of treatment with low doses of flutamide on clinical and hormonal parameters , as well as on the androgen receptor status , in hirsute women .

OBJECTIVE : To investigate the long-term effects of treatment with low doses of flutamide on clinical and hormonal parameters , as well as on the <protein>androgen receptor</protein> status , in hirsute women .


DESIGN : Eighteen hirsute patients with regular menses were studied basally and during treatment with 125 mg flutamide , three times per day for 12 months .


Barrier or intrauterine contraception was used during the study in sexually active women .


Safety parameters were assessed throughout the study .


Hirsutism , graded by the modified Ferriman-Gallwey score , and hormonal parameters were evaluated basally and at 4-month intervals during treatment .


Gonadotropin-releasing hormone and ACTH stimulation tests were performed before and after 3 to 4 months of therapy .


In addition , the concentration of androgen receptors in mononuclear leukocytes was measured , in both the follicular and luteal phases of the menstrual cycle , basally and after 4 months of flutamide treatment .

In addition , the concentration of <protein>androgen receptors</protein> in <cell_type>mononuclear leukocytes</cell_type> was measured , in both the follicular and luteal phases of the menstrual cycle , basally and after 4 months of flutamide treatment .


RESULTS : Flutamide was well tolerated in all women , with the noticeable exception of one patient who presented increased serum transaminase after 8 months of therapy .

RESULTS : Flutamide was well tolerated in all women , with the noticeable exception of one patient who presented increased <protein>serum transaminase</protein> after 8 months of therapy .


Hirsutism markedly improved in all women during the treatment ( Ferriman-Gallwey score after 1 year : 4.1 +/- 0.5 versus 14.1 +/- 0.9 ) .


A reduction of serum androgens was found , whereas no change was observed in either basal or GnRH-stimulated gonadotropins or in the cortisol and 17 alpha-hydroxyprogesterone response to ACTH .


Cycles remained ovulatory .


Before treatment , the number of androgen receptors was higher in the luteal than in the follicular phase .

Before treatment , the number of <protein>androgen receptors</protein> was higher in the luteal than in the follicular phase .


This rhythmic differentiation disappeared after the patients had been given the antiandrogen drug .


CONCLUSIONS : Flutamide is effective in the treatment of hirsutism but requires constant surveillance of liver function .


Androgen receptor blockade might be potentiated by a reduction of serum androgens .


Flutamide affects androgen receptor behavior during the menstrual cycle .

Flutamide affects <protein>androgen receptor</protein> behavior during the menstrual cycle .


The meaning of this finding remains to be elucidated .


Constitutive expression of HIV-1 tat protein in human Jurkat T cells using a BK virus vector .

Constitutive expression of <protein>HIV-1 tat protein</protein> in <cell_line>human Jurkat T cells</cell_line> using a BK virus vector .


The production and characterization of Jurkat cell lines that constitutively express functional human immune deficiency virus type 1 ( HIV-1 ) tat protein , using a BK virus plasmid expression vector and HIV-1 tat cDNA , is described .

The production and characterization of <cell_line>Jurkat cell lines</cell_line> that constitutively express functional <protein>human immune deficiency virus type 1 ( HIV-1 ) tat protein</protein> , using a BK virus plasmid expression vector and <dna>HIV-1 tat cDNA</dna> , is described .


An increased growth rate of these Jurkat-tat cell lines as compared with control cell lines was observed .

An increased growth rate of these <cell_line>Jurkat-tat cell lines</cell_line> as compared with <cell_line>control cell lines</cell_line> was observed .


A PEBP2 alpha/AML-1-related factor increases osteocalcin promoter activity through its binding to an osteoblast-specific cis-acting element .

A <protein>PEBP2 alpha/AML-1-related factor</protein> increases <dna>osteocalcin promoter</dna> activity through its binding to an <dna>osteoblast-specific cis-acting element</dna> .


To identify osteoblast-specific cis-acting elements and trans-acting factors , we initiated an analysis of the promoter of a mouse osteocalcin gene , an osteoblast-specific gene .

To identify <dna>osteoblast-specific cis-acting elements</dna> and <protein>trans-acting factors</protein> , we initiated an analysis of the <dna>promoter</dna> of a <dna>mouse osteocalcin gene</dna> , an <dna>osteoblast-specific gene</dna> .


In this promoter , we identified two osteoblast-specific cis-acting elements ( Ducy , P.and Karsenty , G. ( 1995 ) Mol.Cell.Biol.15 , 1858-1869 ) .

In this promoter , we identified two <dna>osteoblast-specific cis-acting elements</dna> ( Ducy , P.and Karsenty , G. ( 1995 ) Mol.Cell.Biol.15 , 1858-1869 ) .


The sequence of one of these elements , OSE2 , is identical to the DNA-binding site of the PEBP2 alpha/AML-1 transcription factors , the mammalian homologues of the Drosophila Runt protein .

The sequence of one of these <dna>elements</dna> , OSE2 , is identical to the <dna>DNA-binding site</dna> of the <protein>PEBP2 alpha/AML-1 transcription factors</protein> , the <protein>mammalian homologues</protein> of the <protein>Drosophila Runt protein</protein> .


Here we show , using nuclear extracts , recombinant protein , and a specific antiserum against AML-1 proteins in DNA-binding assays , that one member of this family , AML-1B , binds specifically to OSE2 and is immunologically related to OSF2 , the factor present in osteoblast nuclear extracts that binds to OSE2 .

Here we show , using nuclear extracts , <protein>recombinant protein</protein> , and a specific antiserum against <protein>AML-1 proteins</protein> in DNA-binding assays , that one member of this family , <protein>AML-1B</protein> , binds specifically to OSE2 and is immunologically related to <protein>OSF2</protein> , the factor present in osteoblast nuclear extracts that binds to OSE2 .


By DNA cotransfection experiments , we also demonstrate that AML-1B can increase the activity of a short osteocalcin promoter through its binding to OSE2 .

By DNA cotransfection experiments , we also demonstrate that <protein>AML-1B</protein> can increase the activity of a short <dna>osteocalcin promoter</dna> through its binding to OSE2 .


Lastly , the different mobilities of osteoblast nuclear extract-DNA complexes compared with T-cell nuclear extract-DNA complexes , along with the inability of OSF2 to be upregulated by retinoic acid , unlike the other PEBP2 alpha factors , suggest that OSF2 is a new member of this family of transcription factors .

Lastly , the different mobilities of <protein>osteoblast nuclear extract-DNA complexes</protein> compared with <protein>T-cell nuclear extract-DNA complexes</protein> , along with the inability of <protein>OSF2</protein> to be upregulated by retinoic acid , unlike the other <protein>PEBP2 alpha factors</protein> , suggest that <protein>OSF2</protein> is a new member of this family of <protein>transcription factors</protein> .


Thus , this study demonstrates that AML-1B can increase gene expression of an osteoblast-specific gene through its binding to an osteoblast-specific cis-acting element and presents evidence that OSF2 is a member of the PEBP2 alpha/AML-1 family of transcription factors .

Thus , this study demonstrates that <protein>AML-1B</protein> can increase gene expression of an <dna>osteoblast-specific gene</dna> through its binding to an <dna>osteoblast-specific cis-acting element</dna> and presents evidence that <protein>OSF2</protein> is a member of the <protein>PEBP2 alpha/AML-1 family</protein> of <protein>transcription factors</protein> .


Initiation binding repressor , a factor that binds to the transcription initiation site of the histone h5 gene , is a glycosylated member of a family of cell growth regulators [ corrected ] [ published erratum appears in Mol Cell Biol 1996 Feb ; 16 ( 2 ) : 735 ]

<protein>Initiation binding repressor</protein> , a factor that binds to the <dna>transcription initiation site</dna> of the <dna>histone h5 gene</dna> , is a <protein>glycosylated member</protein> of a family of <protein>cell growth regulators</protein> [ corrected ] [ published erratum appears in Mol Cell Biol 1996 Feb ; 16 ( 2 ) : 735 ]


Initiation binding repressor [ corrected ] ( IBR ) is a chicken erythrocyte factor ( apparent molecular mass , 70 to 73 kDa ) that binds to the sequences spanning the transcription initiation site of the histone h5 gene , repressing its transcription .

<protein>Initiation binding repressor</protein> [ corrected ] ( <protein>IBR</protein> ) is a <protein>chicken erythrocyte factor</protein> ( apparent molecular mass , 70 to 73 kDa ) that binds to the sequences spanning the <dna>transcription initiation site</dna> of the <dna>histone h5 gene</dna> , repressing its transcription .


A variety of other cells , including transformed erythroid precursors , do not have IBR but a factor referred to as IBF ( 68 to 70 kDa ) that recognizes the same IBR sites .

A variety of other cells , including <cell_type>transformed erythroid precursors</cell_type> , do not have <protein>IBR</protein> but a factor referred to as <protein>IBF</protein> ( 68 to 70 kDa ) that recognizes the same <protein>IBR</protein> sites .


We have cloned the IBR cDNA and studied the relationship of IBR and IBF .

We have cloned the <dna>IBR cDNA</dna> and studied the relationship of <protein>IBR</protein> and <protein>IBF</protein> .


IBR is a 503-amino-acid-long acidic protein which is 99.0 % identical to the recently reported human NRF-1/alpha-Pal factor and highly related to the invertebrate transcription factors P3A2 and erected wing gene product ( EWG ) .

<protein>IBR</protein> is a <protein>503-amino-acid-long acidic protein</protein> which is 99.0 % identical to the recently reported <protein>human NRF-1/alpha-Pal factor</protein> and highly related to the invertebrate <protein>transcription factors</protein> <protein>P3A2</protein> and <protein>erected wing gene product</protein> ( <protein>EWG</protein> ) .


We present evidence that IBR and IBF are most likely identical proteins , differing in their degree of glycosylation .

We present evidence that <protein>IBR</protein> and <protein>IBF</protein> are most likely identical proteins , differing in their degree of glycosylation .


We have analyzed several molecular aspects of IBR/F and shown that the factor associates as stable homodimers and that the dimer is the relevant DNA-binding species .

We have analyzed several molecular aspects of <protein>IBR/F</protein> and shown that the factor associates as stable <protein>homodimers</protein> and that the <protein>dimer</protein> is the <protein>relevant DNA-binding species</protein> .


The evolutionarily conserved N-terminal half of IBR/F harbors the DNA-binding/dimerization domain ( outer limits , 127 to 283 ) , one or several casein kinase II sites ( 37 to 67 ) , and a bipartite nuclear localization signal ( 89 to 106 ) which appears to be necessary for nuclear targeting .

The evolutionarily conserved <protein>N-terminal half</protein> of <protein>IBR/F</protein> harbors the <protein>DNA-binding/dimerization domain</protein> ( outer limits , 127 to 283 ) , one or several <protein>casein kinase II sites</protein> ( 37 to 67 ) , and a <protein>bipartite nuclear localization signal</protein> ( 89 to 106 ) which appears to be necessary for nuclear targeting .


Binding site selection revealed that the alternating RCGCRYGCGY consensus constitutes high-affinity IBR/F binding sites and that the direct-repeat palindrome TGCGCATGCGCA is the optimal site .

Binding site selection revealed that the <protein>alternating RCGCRYGCGY consensus</protein> constitutes high-affinity <dna>IBR/F binding sites</dna> and that the <dna>direct-repeat palindrome</dna> TGCGCATGCGCA is the <dna>optimal site</dna> .


A survey of genes potentially regulated by this family of factors primarily revealed genes involved in growth-related metabolism .

A survey of <dna>genes</dna> potentially regulated by this family of <protein>factors</protein> primarily revealed <dna>genes</dna> involved in growth-related metabolism .


Triggering of the human interleukin-6 gene by interferon-gamma and tumor necrosis factor-alpha in monocytic cells involves cooperation between interferon regulatory factor-1 , NF kappa B , and Sp1 transcription factors .

Triggering of the human interleukin-6 gene by interferon-gamma and tumor necrosis factor-alpha in monocytic cells involves cooperation between <protein>interferon regulatory factor-1</protein> , <protein>NF kappa B</protein> , and <protein>Sp1</protein> <protein>transcription factors</protein> .


We investigated the molecular basis of the synergistic induction by interferon-gamma ( IFN-gamma ) / tumor necrosis factor-alpha ( TNF-alpha ) of human interleukin-6 ( IL-6 ) gene in THP-1 monocytic cells , and compared it with the basis of this induction by lipopolysaccharide ( LPS ) .

We investigated the molecular basis of the synergistic induction by <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) / <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) of <dna>human interleukin-6 ( IL-6 ) gene</dna> in <cell_type>THP-1 monocytic cells</cell_type> , and compared it with the basis of this induction by lipopolysaccharide ( LPS ) .


Functional studies with IL-6 promoter demonstrated that three regions are the targets of the IFN-gamma and/or TNF-alpha action , whereas only one of these regions seemed to be implicated in LPS activation .

Functional studies with <dna>IL-6 promoter</dna> demonstrated that three regions are the targets of the <protein>IFN-gamma</protein> and/or <protein>TNF-alpha</protein> action , whereas only one of these regions seemed to be implicated in LPS activation .


The three regions concerned are : 1 ) a region between -73 and -36 , which is the minimal element inducible by LPS or TNF-alpha ; 2 ) an element located between -181 and -73 , which appeared to regulate the response to IFN-gamma and TNF-alpha negatively ; and 3 ) a distal element upstream of -224 , which was inducible by IFN-gamma alone .

The three regions concerned are : 1 ) a region between -73 and -36 , which is the <dna>minimal element</dna> inducible by LPS or <protein>TNF-alpha</protein> ; 2 ) an element located between -181 and -73 , which appeared to regulate the response to <protein>IFN-gamma</protein> and <protein>TNF-alpha</protein> negatively ; and 3 ) a <dna>distal element upstream</dna> of -224 , which was inducible by <protein>IFN-gamma</protein> alone .


LPS signaling was found to involve NF kappa B activation by the p50/p65 heterodimers .

LPS signaling was found to involve <protein>NF kappa B</protein> activation by the <protein>p50/p65 heterodimers</protein> .


Synergistic induction of the IL-6 gene by IFN-gamma and TNF-alpha , in monocytic cells , involved cooperation between the IRF-1 and NF kappa B p65 homodimers with concomitant removal of the negative effect of the retinoblastoma control element present in the IL-6 promoter .

Synergistic induction of the <dna>IL-6 gene</dna> by <protein>IFN-gamma</protein> and <protein>TNF-alpha</protein> , in <cell_type>monocytic cells</cell_type> , involved cooperation between the <protein>IRF-1</protein> and <protein>NF kappa B p65 homodimers</protein> with concomitant removal of the negative effect of the <dna>retinoblastoma control element</dna> present in the <dna>IL-6 promoter</dna> .


This removal occurred by activation of the constitutive Sp1 factor , whose increased binding activity and phosphorylation were mediated by IFN-gamma .

This removal occurred by activation of the <protein>constitutive Sp1 factor</protein> , whose increased binding activity and phosphorylation were mediated by <protein>IFN-gamma</protein> .


Mutation of Jak3 in a patient with SCID : essential role of Jak3 in lymphoid development .

Mutation of <protein>Jak3</protein> in a patient with SCID : essential role of <protein>Jak3</protein> in lymphoid development .


Males with X-linked severe combined immunodeficiency ( XSCID ) have defects in the common cytokine receptor gamma chain ( gamma c ) gene that encodes a shared , essential component of the receptors of interleukin-2 ( IL-2 ) , IL-4 , IL-7 , IL-9 , and IL-15 .

Males with X-linked severe combined immunodeficiency ( XSCID ) have defects in the common <dna>cytokine receptor gamma chain ( gamma c ) gene</dna> that encodes a shared , essential component of the receptors of <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) , <protein>IL-4</protein> , <protein>IL-7</protein> , <protein>IL-9</protein> , and <protein>IL-15</protein> .


The Janus family tyrosine kinase Jak3 is the only signaling molecule known to be associated with gamma c , so it was hypothesized that defects in Jak3 might cause an XSCID-like phenotype .

The <protein>Janus family tyrosine kinase</protein> <protein>Jak3</protein> is the only signaling molecule known to be associated with <protein>gamma c</protein> , so it was hypothesized that defects in <protein>Jak3</protein> might cause an XSCID-like phenotype .


A girl with immunological features indistinguishable from those of XSCID was therefore selected for analysis .


An Epstein-Barr virus ( EBV ) -transformed cell line derived from her lymphocytes had normal gamma c expression but lacked Jak3 protein and had greatly diminished Jak3 messenger RNA .

An <cell_line>Epstein-Barr virus ( EBV ) -transformed cell line</cell_line> derived from her <cell_type>lymphocytes</cell_type> had normal <protein>gamma c</protein> expression but lacked <protein>Jak3 protein</protein> and had greatly diminished <rna>Jak3 messenger RNA</rna> .


Sequencing revealed a different mutation on each allele : a single nucleotide insertion resulting in a frame shift and premature termination in the Jak3 JH4 domain and a nonsense mutation in the Jak3 JH2 domain .

Sequencing revealed a different mutation on each allele : a single nucleotide insertion resulting in a frame shift and premature termination in the <protein>Jak3 JH4 domain</protein> and a nonsense mutation in the <protein>Jak3</protein> JH2 domain .


The lack of Jak3 expression correlated with impaired B cell signaling , as demonstrated by the inability of IL-4 to activate Stat6 in the EBV-transformed cell line from the patient. These observations indicate that the functions of gamma c are dependent on Jak3 and that Jak3 is essential for lymphoid development and signaling .

The lack of <protein>Jak3</protein> expression correlated with impaired B cell signaling , as demonstrated by the inability of <protein>IL-4</protein> to activate <protein>Stat6</protein> in the <cell_line>EBV-transformed cell line</cell_line> from the patient. These observations indicate that the functions of <protein>gamma c</protein> are dependent on <protein>Jak3</protein> and that <protein>Jak3</protein> is essential for lymphoid development and signaling .


Constitutive overexpression of the L-selectin gene in fresh leukemic cells of adult T-cell leukemia that can be transactivated by human T-cell lymphotropic virus type 1 Tax .

Constitutive overexpression of the <dna>L-selectin gene</dna> in fresh <cell_type>leukemic cells</cell_type> of adult T-cell leukemia that can be transactivated by <protein>human T-cell lymphotropic virus type 1 Tax</protein> .


L-selectin is an adhesion molecule of the selectin family that mediates the initial step of leukocyte adhesion to vascular endothelium .

<protein>L-selectin</protein> is an adhesion molecule of the selectin family that mediates the initial step of leukocyte adhesion to vascular endothelium .


Upon cellular activation , expression of the L-selectin gene is downregulated at both the protein and mRNA levels .

Upon cellular activation , expression of the <dna>L-selectin gene</dna> is downregulated at both the protein and mRNA levels .


To understand the mechanism of leukemic cell infiltration into organs , we studied the expression and regulation of L-selectin mRNA in fresh leukemic cells of adult T-cell leukemia ( ATL ) patients and investigated the response of the L-selectin promoter to human T-cell lymphotropic virus type 1 ( HTLV-1 ) Tax , which is a viral transcriptional transactivator .

To understand the mechanism of <cell_type>leukemic cell</cell_type> infiltration into organs , we studied the expression and regulation of <rna>L-selectin mRNA</rna> in fresh <cell_type>leukemic cells</cell_type> of adult T-cell leukemia ( ATL ) patients and investigated the response of the <dna>L-selectin promoter</dna> to <protein>human T-cell lymphotropic virus type 1 ( HTLV-1 ) Tax</protein> , which is a <protein>viral transcriptional transactivator</protein> .


Flow cytometry showed that L-selectin was expressed on fresh ATL cells along with other activation antigens .

Flow cytometry showed that <protein>L-selectin</protein> was expressed on fresh <cell_line>ATL cells</cell_line> along with other <protein>activation antigens</protein> .


Northern blot analysis showed that ATL cells overexpressed that L-selectin mRNA and that the level was aberrantly upregulated after PMA stimulation .

Northern blot analysis showed that <cell_line>ATL cells</cell_line> overexpressed that <rna>L-selectin mRNA</rna> and that the level was aberrantly upregulated after PMA stimulation .


Studies using in situ hybridization showed expression of the L-selectin mRNA in the infiltrating leukemic cells in the liver of two ATL patients .

Studies using in situ hybridization showed expression of the <rna>L-selectin mRNA</rna> in the infiltrating <cell_type>leukemic cells</cell_type> in the liver of two ATL patients .


Intravenous injection of a rat T-cell line that overexpresses L-selectin showed increased organ infiltration .

Intravenous injection of a <cell_line>rat T-cell line</cell_line> that overexpresses <protein>L-selectin</protein> showed increased organ infiltration .


The induction of Tax expression in JPX9 cells resulted in about a twofold increase in the mRNA expression levels compared with the basal level .

The induction of <protein>Tax</protein> expression in <cell_line>JPX9 cells</cell_line> resulted in about a twofold increase in the <rna>mRNA</rna> expression levels compared with the basal level .


Chloramphenicol acetyltransferase ( CAT ) assay after transient cotransfection showed about a fivefold transactivation of the L-selectin promoter by Tax .

<protein>Chloramphenicol acetyltransferase</protein> ( <protein>CAT</protein> ) assay after transient cotransfection showed about a fivefold transactivation of the <dna>L-selectin promoter</dna> by <protein>Tax</protein> .


The serum level of the shed form of L-selectin was significantly increased in ATL patients ( mean +/- SD , 4 , 215.4 +/- 4 , 111 ng/mL ) compared with those of asymptomatic carriers and healthy blood donors ( mean +/- SD , 1 , 148.0 +/- 269.0 ng/mL and 991.9 +/- 224 ng/mL , respectively ) .

The serum level of the shed form of <protein>L-selectin</protein> was significantly increased in ATL patients ( mean +/- SD , 4 , 215.4 +/- 4 , 111 ng/mL ) compared with those of asymptomatic carriers and healthy blood donors ( mean +/- SD , 1 , 148.0 +/- 269.0 ng/mL and 991.9 +/- 224 ng/mL , respectively ) .


These results indicated that ATL cells constitutively overexpress the L-selectin gene that can be transactivated by HTLV-1 Tax .

These results indicated that <cell_line>ATL cells</cell_line> constitutively overexpress the <dna>L-selectin gene</dna> that can be transactivated by HTLV-1 <protein>Tax</protein> .


The overexpression of L-selectin , as well as of inflammatory cytokines , by ATL cells may provide a basis for ATL cells to attach the vascular endothelium , leading to transmigration and organ infitration .

The overexpression of <protein>L-selectin</protein> , as well as of <protein>inflammatory cytokines</protein> , by <cell_line>ATL cells</cell_line> may provide a basis for <cell_line>ATL cells</cell_line> to attach the vascular endothelium , leading to transmigration and organ infitration .


Human herpesvirus 6 variant A , but not variant B , infects EBV-positive B lymphoid cells , activating the latent EBV genome through a BZLF-1 -dependent mechanism .

Human herpesvirus 6 variant A , but not variant B , infects <cell_line>EBV-positive B lymphoid cells</cell_line> , activating the <dna>latent EBV genome</dna> through a <protein>BZLF-1</protein> -dependent mechanism .


Human herpesvirus 6 , a predominantly T lymphotropic virus , has been recently shown to infect some EBV-positive B cell lines , and to induce in them the activation of the EBV lytic cycle .

Human herpesvirus 6 , a predominantly T lymphotropic virus , has been recently shown to infect some <cell_line>EBV-positive B cell lines</cell_line> , and to induce in them the activation of the EBV lytic cycle .


Here we have confirmed and extended such observations , showing that ( 1 ) this phenomenon is restricted to the variant A of HHV-6 : in fact two isolates belonging to the HHV-6 variant B ( BA92 and Z29 ) were neither able to infect any B cell line , independently of the EBV status , nor to induce the EBV genome expression .

Here we have confirmed and extended such observations , showing that ( 1 ) this phenomenon is restricted to the variant A of HHV-6 : in fact two isolates belonging to the HHV-6 variant B ( BA92 and Z29 ) were neither able to infect any <cell_line>B cell line</cell_line> , independently of the EBV status , nor to induce the EBV genome expression .


The only exception is represented by the P3HR1 cells , in which , however , the infection by the variant B does not determine induction of EBV antigens ; ( 2 ) the presence of the EBV genome contributes to the susceptibility of the B cell lines to HHV-6 infection , increasing the binding sites and the percentage of infectable cells , as detected by immunoelectron microscopy ; and ( 3 ) HHV-6 infected T cells , transfected with plasmids bearing the promoter regions of the EBV early genes BZLF1 and BMRF1 , show a strong transactivation of these promoters .

The only exception is represented by the <cell_line>P3HR1 cells</cell_line> , in which , however , the infection by the variant B does not determine induction of <protein>EBV antigens</protein> ; ( 2 ) the presence of the <dna>EBV genome</dna> contributes to the susceptibility of the <cell_line>B cell lines</cell_line> to HHV-6 infection , increasing the binding sites and the percentage of <cell_type>infectable cells</cell_type> , as detected by immunoelectron microscopy ; and ( 3 ) <cell_line>HHV-6 infected T cells</cell_line> , transfected with <dna>plasmids</dna> bearing the <dna>promoter regions</dna> of the EBV early genes BZLF1 and <dna>BMRF1</dna> , show a strong transactivation of these <dna>promoters</dna> .


Evidence for normal vitamin D receptor messenger ribonucleic acid and genotype in absorptive hypercalciuria .

Evidence for normal <rna>vitamin D receptor messenger ribonucleic acid</rna> and genotype in absorptive hypercalciuria .


Absorptive hypercalciuria ( a stone-forming condition ) is characterized by gut hyperabsorption of calcium , hypercalciuria , and reduced bone density .


Inasmuch as these features implicate enhanced calcitriol action in gut and bone , we analyzed the vitamin D receptor ( VDR ) gene to ascertain whether an abnormality of this gene marks patients with intestinal hyperabsorption of calcium .

Inasmuch as these features implicate enhanced calcitriol action in gut and bone , we analyzed the <dna>vitamin D receptor ( VDR ) gene</dna> to ascertain whether an abnormality of this gene marks patients with intestinal hyperabsorption of calcium .


We have compared the frequency of a restriction fragment length polymorphism ( Bsm I ) associated with different alleles of the VDR gene in a group of 33 well characterized absorptive hypercalciuric patients and a group of 36 normal race- and age-matched control subjects .

We have compared the frequency of a <dna>restriction fragment length polymorphism</dna> ( Bsm I ) associated with different alleles of the <dna>VDR gene</dna> in a group of 33 well characterized absorptive hypercalciuric patients and a group of 36 normal race- and age-matched control subjects .


There was no difference between the distribution of the VDR alleles in the patient population when compared with the normal population .

There was no difference between the distribution of the <protein>VDR</protein> alleles in the patient population when compared with the normal population .


The coding region of VDR messenger RNA was also normal , as determined by both DNA sequence analysis and chemical mismatch cleavage analysis of copy DNA from 11 index absorptive hypercalciuric patients .

The coding region of <rna>VDR messenger RNA</rna> was also normal , as determined by both <dna>DNA sequence</dna> analysis and chemical mismatch cleavage analysis of copy DNA from 11 index absorptive hypercalciuric patients .


On the basis of these results , we propose that the enhanced intestinal calcium absorption invariably seen in absorptive hypercalciuria and attendant symptoms of this disorder are not attributable to mutations of the VDR and are not linked to a common VDR genotype .

On the basis of these results , we propose that the enhanced intestinal calcium absorption invariably seen in absorptive hypercalciuria and attendant symptoms of this disorder are not attributable to mutations of the <protein>VDR</protein> and are not linked to a common <dna>VDR genotype</dna> .


Transcriptional regulation of the gene encoding the human C-type lectin leukocyte receptor AIM/CD69 and functional characterization of its tumor necrosis factor-alpha-responsive elements .

Transcriptional regulation of the gene encoding the <protein>human C-type lectin leukocyte receptor</protein> <protein>AIM/CD69</protein> and functional characterization of its <dna>tumor necrosis factor-alpha-responsive elements</dna> .


The human activation antigen CD69 is a member of the C-type animal lectin superfamily that functions as a signal-transmitting receptor .

The <protein>human activation antigen</protein> <protein>CD69</protein> is a member of the <protein>C-type animal lectin superfamily</protein> that functions as a <protein>signal-transmitting receptor</protein> .


Although the expression of CD69 can be induced in vitro on cells of most hematopoietic lineages with a wide variety of stimuli , in vivo it is mainly expressed by T-lymphocytes located in the inflammatory infiltrates of several human diseases .

Although the expression of <protein>CD69</protein> can be induced in vitro on cells of most hematopoietic lineages with a wide variety of stimuli , in vivo it is mainly expressed by <cell_type>T-lymphocytes</cell_type> located in the inflammatory infiltrates of several human diseases .


To elucidate the mechanisms that regulate the constitutive and inducible expression of CD69 by leukocytes , we isolated the promoter region of the CD69 gene and carried out its functional characterization .

To elucidate the mechanisms that regulate the constitutive and inducible expression of <protein>CD69</protein> by <cell_type>leukocytes</cell_type> , we isolated the <dna>promoter region</dna> of the <protein>CD69</protein> gene and carried out its functional characterization .


Sequence analysis of the 5'-flanking region of the CD69 gene revealed the presence of a potential TATA element 30 base pairs upstream of the major transcription initiation site and several putative binding sequences for inducible transcription factors ( NF-kappa B , Egr-1 , AP-1 ) , which might mediate the inducible expression of this gene .

Sequence analysis of the <dna>5'-flanking region</dna> of the <dna>CD69 gene</dna> revealed the presence of a potential <dna>TATA element</dna> <dna>30 base pairs upstream</dna> of the major <dna>transcription initiation site</dna> and several putative binding sequences for inducible <protein>transcription factors</protein> ( <protein>NF-kappa B</protein> , <protein>Egr-1</protein> , <protein>AP-1</protein> ) , which might mediate the inducible expression of this gene .


Transient expression of CD69 promoter-based reporter gene constructs in K562 cells indicated that the proximal promoter region spanning positions -78 to +16 contained the cis-acting sequences necessary for basal and phorbol 12-myristate 13-acetate-inducible transcription of the CD69 gene .

Transient expression of <dna>CD69 promoter-based reporter gene constructs</dna> in <cell_line>K562 cells</cell_line> indicated that the <dna>proximal promoter region</dna> spanning positions -78 to +16 contained the <dna>cis-acting sequences</dna> necessary for basal and phorbol 12-myristate 13-acetate-inducible transcription of the <dna>CD69 gene</dna> .


Removal of the upstream sequences located between positions -78 and -38 resulted in decreased promoter strength and abolished the response to phorbol 12-myristate 13-acetate .


We also found that tumor necrosis factor-alpha ( TNF-alpha ) is capable of inducing the surface expression of the CD69 molecule as well as the promoter activity of fusion plasmids that contain 5'-flanking sequences of the CD69 gene , suggesting that this cytokine may regulate in vivo the expression of CD69 .

We also found that <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) is capable of inducing the surface expression of the <protein>CD69</protein> molecule as well as the promoter activity of fusion plasmids that contain 5'-flanking sequences of the <protein>CD69</protein> gene , suggesting that this cytokine may regulate in vivo the expression of <protein>CD69</protein> .


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Characterization of 5 ' end of human thromboxane receptor gene .

Characterization of <dna>5 ' end of human thromboxane receptor gene</dna> .


Organizational analysis and mapping of protein kinase C -- responsive elements regulating expression in platelets .

Organizational analysis and mapping of <dna>protein kinase C -- responsive elements</dna> regulating expression in <cell_type>platelets</cell_type> .


Platelet thromboxane receptors are acutely and reversibly upregulated after acute myocardial infarction .

<protein>Platelet thromboxane receptors</protein> are acutely and reversibly upregulated after acute myocardial infarction .


To determine if platelet thromboxane receptors are under transcriptional control , we isolated and characterized human genomic DNA clones containing the 5 ' flanking region of the thromboxane receptor gene .

To determine if platelet <protein>thromboxane receptors</protein> are under transcriptional control , we isolated and characterized <dna>human genomic DNA clones</dna> containing the <dna>5 ' flanking region</dna> of the <dna>thromboxane receptor gene</dna> .


The exon-intron structure of the 5 ' portion of the thromboxane receptor gene was determined initially by comparing the nucleotide sequence of the 5 ' flanking genomic clone with that of a novel human uterine thromboxane receptor cDNA that extended the mRNA 141 bp further upstream than the previously identified human placental cDNA .

The <dna>exon-intron structure</dna> of the <dna>5 ' portion</dna> of the <dna>thromboxane receptor gene</dna> was determined initially by comparing the <dna>nucleotide sequence</dna> of the <dna>5 ' flanking genomic clone</dna> with that of a <dna>novel human uterine thromboxane receptor cDNA</dna> that extended the <rna>mRNA</rna> <dna>141 bp further upstream</dna> than the <dna>previously identified human placental cDNA</dna> .


A major transcription initiation site was located in three human tissues approximately 560 bp upstream from the translation initiation codon and 380 bp upstream from any previously identified transcription initiation site .

A major <dna>transcription initiation site</dna> was located in three human tissues approximately <dna>560 bp upstream</dna> from the <dna>translation initiation codon</dna> and <dna>380 bp upstream</dna> from any previously identified <dna>transcription initiation site</dna> .


The thromboxane receptor gene has neither a TATA nor a CAAT consensus site .

The <dna>thromboxane receptor gene</dna> has neither a <dna>TATA</dna> nor a <dna>CAAT consensus site</dna> .


Promoter function of the 5 ' flanking region of the thromboxane receptor gene was evaluated by transfection of thromboxane receptor gene promoter/chloramphenicol acetyltransferase ( CAT ) chimera plasmids into platelet-like K562 cells .

Promoter function of the <dna>5 ' flanking region</dna> of the <dna>thromboxane receptor gene</dna> was evaluated by transfection of <dna>thromboxane receptor gene promoter/chloramphenicol acetyltransferase ( CAT ) chimera plasmids</dna> into platelet-like <cell_line>K562 cells</cell_line> .


Thromboxane receptor promoter activity , as assessed by CAT expression , was relatively weak but was significantly enhanced by phorbol ester treatment .

Thromboxane <dna>receptor promoter</dna> activity , as assessed by <protein>CAT</protein> expression , was relatively weak but was significantly enhanced by phorbol ester treatment .


Functional analysis of 5 ' deletion constructs in transfected K562 cells and gel mobility shift localized the major phorbol ester-responsive motifs in the thromboxane receptor gene promoter to a cluster of activator protein-2 ( AP-2 ) binding consensus sites located approximately 1.8 kb 5 ' from the transcription initiation site .

Functional analysis of <dna>5 ' deletion constructs</dna> in transfected <cell_line>K562 cells</cell_line> and gel mobility shift localized the major phorbol ester-responsive motifs in the <dna>thromboxane receptor gene</dna> promoter to a cluster of <dna>activator protein-2 ( AP-2 ) binding consensus sites</dna> located approximately 1.8 kb 5 ' from the <dna>transcription initiation site</dna> .


These studies are the first to determine the structure and organization of the 5 ' end of the thromboxane receptor gene and demonstrate that thromboxane receptor gene expression can be regulated by activation of protein kinase C via induction of an AP-2-like nuclear factor binding to upstream promoter elements .

These studies are the first to determine the structure and organization of the 5 ' end of the <dna>thromboxane receptor gene</dna> and demonstrate that <dna>thromboxane receptor gene</dna> expression can be regulated by activation of <protein>protein kinase C</protein> via induction of an <protein>AP-2-like nuclear factor</protein> binding to <dna>upstream promoter elements</dna> .


These findings strongly suggest that the mechanism for previously described upregulation of platelet thromboxane receptors after acute myocardial infarction is increased thromboxane receptor gene transcription in platelet-progenitor cells .

These findings strongly suggest that the mechanism for previously described upregulation of <protein>platelet thromboxane receptors</protein> after acute myocardial infarction is increased <dna>thromboxane receptor gene</dna> transcription in <cell_type>platelet-progenitor cells</cell_type> .


Estrogen receptor concentration and social factors as predictors of natural killer cell activity in early-stage breast cancer patients .

<protein>Estrogen receptor</protein> concentration and social factors as predictors of natural killer cell activity in early-stage breast cancer patients .


Confirmation of a model .


Previous work of ours has demonstrated that a significant amount of natural killer ( NK ) activity variance after surgery in stage I and II breast cancer patients could be accounted for by both the estrogen receptor ( ER ) status of the tumor and by social factors , namely , perceived social support and seeking social support as a general coping strategy .

Previous work of ours has demonstrated that a significant amount of natural killer ( NK ) activity variance after surgery in stage I and II breast cancer patients could be accounted for by both the <protein>estrogen receptor</protein> ( <protein>ER</protein> ) status of the tumor and by social factors , namely , perceived social support and seeking social support as a general coping strategy .


As considerable evidence has accumulated that social support in both animal and human populations may have survival value , we sought to test the reliability of this regression model , using coping and perceived support factor values obtained at 3 months after surgery to account for concurrent follow-up NK activity in this serially assessed group of patients .


It was found that the most significant variable predicting NK activity at follow-up was tumor ER concentration , with higher NK activity associated with ER -status .

It was found that the most significant variable predicting NK activity at follow-up was tumor <protein>ER</protein> concentration , with higher NK activity associated with <protein>ER</protein> -status .


In addition , seeking social support as a coping strategy , as well as the perceived quality of support , also entered the model to account for a significant amount of NK activity variance ( multivariate F = 5.25 , p less than 0.001 ) .


If , as the literature suggests , NK activity is relevant to breast cancer control , and since ER -tumors have a worse prognosis , we suggest here that perhaps such tumors are resistant to control by NK cells because they lack the ability to attract an accumulation of effector cells to the tumor site , or because blocking factors at the site of the tumor prevent local tumor control at the site of action .

If , as the literature suggests , NK activity is relevant to breast cancer control , and since <protein>ER</protein> -tumors have a worse prognosis , we suggest here that perhaps such tumors are resistant to control by <cell_type>NK cells</cell_type> because they lack the ability to attract an accumulation of <cell_type>effector cells</cell_type> to the tumor site , or because blocking factors at the site of the tumor prevent local tumor control at the site of action .


The finding related to social support also replicates results from an independent sample of breast cancer patients .


This finding , taken together with other evidence that this social variable is associated with longer survival in breast cancer populations , underscores the potential importance of this social support variable .


Our findings also suggest one possible immunological variable involved , with potential clinical significance , for this patient population .


Solution structure of the sequence-specific HMG box of the lymphocyte transcriptional activator Sox-4 .

Solution structure of the <dna>sequence-specific HMG box</dna> of the <protein>lymphocyte transcriptional activator</protein> <protein>Sox-4</protein> .


Two groups of HMG box proteins are distinguished .

Two groups of <protein>HMG box proteins</protein> are distinguished .


Proteins in the first group contain multiple HMG boxes , are non-sequence-specific , and recognize structural features as found in cruciform DNA and cross-over DNA .

Proteins in the first group contain multiple <protein>HMG boxes</protein> , are non-sequence-specific , and recognize structural features as found in <dna>cruciform DNA</dna> and <dna>cross-over DNA</dna> .


The abundant chromosomal protein HMG-1 belongs to this subgroup .

The abundant <protein>chromosomal protein</protein> <protein>HMG-1</protein> belongs to this subgroup .


Proteins in the second group carry a single HMG box with affinity for the minor groove of the heptamer motif AACAAAG or variations thereof .

Proteins in the second group carry a <protein>single HMG box</protein> with affinity for the minor groove of the <dna>heptamer motif</dna> AACAAAG or variations thereof .


A solution structure for the non-sequence-specific C-terminal HMG box of HMG-1 has recently been proposed .

A solution structure for the non-sequence-specific <protein>C-terminal HMG box</protein> of <protein>HMG-1</protein> has recently been proposed .


Now , we report the solution structure of the sequence-specific HMG-box of the SRY-related protein Sox-4 .

Now , we report the solution structure of the <protein>sequence-specific HMG-box</protein> of the <protein>SRY-related protein</protein> <protein>Sox-4</protein> .


NMR analysis demonstrated the presence of three alpha-helices ( Val10-Gln22 , Glu30-Leu41 and Phe50-Tyr65 ) connected by loop regions ( Ser23-Ala49 and Leu42-Pro49 ) .

NMR analysis demonstrated the presence of three <protein>alpha-helices</protein> ( <protein>Val10-Gln22</protein> , <protein>Glu30-Leu41</protein> and <protein>Phe50-Tyr65</protein> ) connected by <protein>loop regions</protein> ( <protein>Ser23-Ala49</protein> and <protein>Leu42-Pro49</protein> ) .


Helices I and II are positioned in an antiparallel mode and form one arm of the HMG box .

<protein>Helices I and II</protein> are positioned in an <protein>antiparallel mode</protein> and form one arm of the <protein>HMG box</protein> .


Helix III is less rigid , makes an average angle of about 90 degrees with helices I and II , and constitutes the other arm of the molecule .

<protein>Helix III</protein> is less rigid , makes an average angle of about 90 degrees with <protein>helices I and II</protein> , and constitutes the other arm of the molecule .


As in HMG1B , the overall structure of the Sox-4 HMG box is L-shaped and is maintained by a cluster of conserved , mainly aromatic residues .

As in <protein>HMG1B</protein> , the overall structure of the <protein>Sox-4</protein> <protein>HMG box</protein> is L-shaped and is maintained by a cluster of conserved , mainly aromatic residues .


Nuclear factor-IL6 activates the human IL-4 promoter in T cells .

<protein>Nuclear factor-IL6</protein> activates the <dna>human IL-4 promoter</dna> in <cell_type>T cells</cell_type> .


Positive regulatory element I ( PRE-I ) is a strong enhancer element essential for expression of the human IL-4 gene .

<dna>Positive regulatory element I</dna> ( <dna>PRE-I</dna> ) is a strong <dna>enhancer element</dna> essential for expression of the <dna>human IL-4 gene</dna> .


To identify transcription factors binding to PRE-I , we screened a cDNA expression library from Jurkat T cells and isolated a cDNA encoding nuclear factor ( NF ) -IL6 ( also known as C/EBP beta ) .

To identify <protein>transcription factors</protein> binding to <dna>PRE-I</dna> , we screened a <dna>cDNA expression library</dna> from <cell_line>Jurkat T cells</cell_line> and isolated a <dna>cDNA</dna> encoding <protein>nuclear factor</protein> <protein>( NF ) -IL6</protein> ( also known as <protein>C/EBP beta</protein> ) .


NF-IL6 mRNA was found in human Jurkat T cells and in the mouse Th2 clone D10 , but not in Th1 clone 29 .

<rna>NF-IL6 mRNA</rna> was found in <cell_line>human Jurkat T cells</cell_line> and in the <cell_line>mouse Th2 clone</cell_line> <cell_line>D10</cell_line> , but not in <cell_line>Th1 clone 29</cell_line> .


rNF-IL6 expressed in bacteria was shown to specifically bind to PRE-I .

<protein>rNF-IL6</protein> expressed in bacteria was shown to specifically bind to <dna>PRE-I</dna> .


PRE-I forms multiple DNA-protein complexes with nuclear extracts from Jurkat cells .

<dna>PRE-I</dna> forms <protein>multiple DNA-protein complexes</protein> with nuclear extracts from <cell_line>Jurkat cells</cell_line> .


Some of these complexes were demonstrated to contain NF-IL6 by using anti-C/EBP beta Abs .

Some of these complexes were demonstrated to contain <protein>NF-IL6</protein> by using <protein>anti-C/EBP beta Abs</protein> .


Overexpression of NF-IL6 enhanced expression of the chloramphenicol acetyl transferase reporter gene linked to the PRE-I-thymidine kinase or the human IL-4 promoter more than 10-fold in Jurkat cells .

Overexpression of <protein>NF-IL6</protein> enhanced expression of the <dna>chloramphenicol acetyl transferase reporter gene</dna> linked to the <protein>PRE-I-thymidine kinase</protein> or the <dna>human IL-4 promoter</dna> more than 10-fold in <cell_line>Jurkat cells</cell_line> .


Promoter deletion studies revealed two additional NF-IL6 binding sites located at positions -44 to -36 ( C/EBP proximal ) and -87 to -79 ( C/EBP medial ) , respectively .

Promoter deletion studies revealed two additional <dna>NF-IL6 binding sites</dna> located at positions -44 to -36 ( <protein>C/EBP proximal</protein> ) and -87 to -79 ( <protein>C/EBP medial</protein> ) , respectively .


Our results demonstrate that NF-IL6 is involved in transcriptional activation of the human IL-4 promoter in T cells .

Our results demonstrate that <protein>NF-IL6</protein> is involved in transcriptional activation of the <dna>human IL-4 promoter</dna> in <cell_type>T cells</cell_type> .


Identification of an I kappa B alpha-associated protein kinase in a human monocytic cell line and determination of its phosphorylation sites on I kappa B alpha .

Identification of an <protein>I kappa B alpha-associated protein kinase</protein> in a <cell_line>human monocytic cell line</cell_line> and determination of its <protein>phosphorylation sites</protein> on <protein>I kappa B alpha</protein> .


Nuclear factor kappa B ( NF-kappa B ) is stored in the cytoplasm as an inactive form through interaction with I kappa B .

<protein>Nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) is stored in the cytoplasm as an inactive form through interaction with <protein>I kappa B</protein> .


Stimulation of cells leads to a rapid phosphorylation of I kappa B alpha , which is presumed to be important for the subsequent degradation .

Stimulation of cells leads to a rapid phosphorylation of <protein>I kappa B alpha</protein> , which is presumed to be important for the subsequent degradation .


We have recently reported the establishment of a lipopolysaccharide ( LPS ) -dependent cell-free activation system of NF-kappa B in association with the induction of I kappa B alpha phosphorylation .

We have recently reported the establishment of a lipopolysaccharide ( LPS ) -dependent cell-free activation system of <protein>NF-kappa B</protein> in association with the induction of <protein>I kappa B alpha</protein> phosphorylation .


In this study , we have identified a kinase in cell extracts from the LPS-stimulated human monocytic cell line , THP-1 , that specifically binds and phosphorylates I kappa B alpha .

In this study , we have identified a <protein>kinase</protein> in cell extracts from the <cell_line>LPS-stimulated human monocytic cell line</cell_line> , <cell_line>THP-1</cell_line> , that specifically binds and phosphorylates <protein>I kappa B alpha</protein> .


LPS stimulation transiently enhanced the I kappa B alpha -bound kinase activity in THP-1 cells .

LPS stimulation transiently enhanced the <protein>I kappa B alpha</protein> <protein>-bound kinase</protein> activity in <cell_line>THP-1 cells</cell_line> .


Mutational analyses of I kappa B alpha and competition experiments with the synthetic peptides identified major phosphorylation sites by the bound kinase as Ser and Thr residues in the C-terminal acidic domain of I kappa B alpha .

Mutational analyses of <protein>I kappa B</protein> alpha and competition experiments with the synthetic peptides identified major <protein>phosphorylation sites</protein> by the bound <protein>kinase</protein> as Ser and Thr residues in the <protein>C-terminal acidic domain</protein> of <protein>I kappa B alpha</protein> .


Moreover , we show that the peptide , corresponding to the C-terminal acidic domain of I kappa B alpha , blocked the LPS-induced NF-kappa B activation as well as inducible phosphorylation of endogenous I kappa B alpha in a cell-free system using THP-1 cells .

Moreover , we show that the peptide , corresponding to the <protein>C-terminal acidic domain</protein> of <protein>I kappa B alpha</protein> , blocked the LPS-induced <protein>NF-kappa B</protein> activation as well as inducible phosphorylation of endogenous <protein>I kappa B alpha</protein> in a cell-free system using <cell_line>THP-1 cells</cell_line> .


These results suggested that the bound kinase is involved in the signaling pathway of LPS by inducing the phosphorylation of the C-terminal region of I kappa B alpha and subsequent dissociation of the NF-kappa B . I kappa B alpha complex .

These results suggested that the <protein>bound kinase</protein> is involved in the signaling pathway of LPS by inducing the phosphorylation of the <protein>C-terminal region</protein> of <protein>I kappa B alpha</protein> and subsequent dissociation of the <protein>NF-kappa B</protein> . <protein>I kappa B alpha complex</protein> .


Bik , a novel death-inducing protein shares a distinct sequence motif with Bcl-2 family proteins and interacts with viral and cellular survival-promoting proteins .

<protein>Bik</protein> , a novel <protein>death-inducing protein</protein> shares a distinct sequence motif with <protein>Bcl-2 family proteins</protein> and interacts with viral and <protein>cellular survival-promoting proteins</protein> .


The survival-promoting activity of the Bcl-2 family of proteins appears to be modulated by interactions between various cellular proteins .

The survival-promoting activity of the <protein>Bcl-2 family</protein> of proteins appears to be modulated by interactions between various <protein>cellular proteins</protein> .


We have identified a novel cellular protein , Bik , that interacts with the cellular survival-promoting proteins , Bcl-2 and Bcl-xL , as well as the viral survival-promoting proteins , Epstein Barr virus-BHRF1 and adenovirus E1B-19 kDa .

We have identified a novel <protein>cellular protein</protein> , <protein>Bik</protein> , that interacts with the <protein>cellular survival-promoting proteins</protein> , <protein>Bcl-2</protein> and <protein>Bcl-xL</protein> , as well as the <protein>viral survival-promoting proteins</protein> , <protein>Epstein Barr virus-BHRF1</protein> and <protein>adenovirus E1B-19 kDa</protein> .


In transient transfection assays , Bik promotes cell death in a manner similar to the death-promoting members of the Bcl-2 family , Bax and Bak .

In transient transfection assays , <protein>Bik</protein> promotes cell death in a manner similar to the <protein>death-promoting members</protein> of the <protein>Bcl-2 family</protein> , <protein>Bax</protein> and <protein>Bak</protein> .


This death-promoting activity of Bik can be suppressed by coexpression of Bcl-2 , Bcl-XL , EBV-BHRF1 and E1B-19 kDa proteins suggesting that Bik may be a common target for both cellular and viral anti-apoptotic proteins .

This death-promoting activity of <protein>Bik</protein> can be suppressed by coexpression of <protein>Bcl-2</protein> , <protein>Bcl-XL</protein> , <protein>EBV-BHRF1</protein> and <protein>E1B-19 kDa</protein> proteins suggesting that <protein>Bik</protein> may be a common target for both <protein>cellular and viral anti-apoptotic proteins</protein> .


While Bik does not show overt homology to the BH1 and BH2 conserved domains characteristic of the Bcl-2 family , it does share a 9 amino acid domain ( BH3 ) with Bax and Bak which may be a critical determinant for the death-promoting activity of these proteins .

While <protein>Bik</protein> does not show overt homology to the <protein>BH1</protein> and <protein>BH2</protein> conserved domains characteristic of the <protein>Bcl-2 family</protein> , it does share a 9 <protein>amino acid domain</protein> ( <protein>BH3</protein> ) with <protein>Bax</protein> and <protein>Bak</protein> which may be a critical determinant for the death-promoting activity of these proteins .


The human TCF-1 gene encodes a nuclear DNA-binding protein uniquely expressed in normal and neoplastic T-lineage lymphocytes .

The <dna>human TCF-1 gene</dna> encodes a <protein>nuclear DNA-binding protein</protein> uniquely expressed in <cell_line>normal and neoplastic T-lineage lymphocytes</cell_line> .


The TCF-1 gene encodes a putative transcription factor with affinity for a sequence motif occurring in a number of T-cell enhancers .

The <dna>TCF-1 gene</dna> encodes a <protein>putative transcription factor</protein> with affinity for a sequence motif occurring in a number of <dna>T-cell enhancers</dna> .


TCF-1 mRNA was originally found to be expressed in a T cell-specific fashion within a set of human and mouse cell lines .

<rna>TCF-1 mRNA</rna> was originally found to be expressed in a T cell-specific fashion within a set of <cell_line>human and mouse cell lines</cell_line> .


In contrast , expression reportedly occurs in multiple nonlymphoid tissues during murine embryogenesis .


We have now raised a monoclonal antibody to document expression and biochemistry of the human TCF-1 protein .

We have now raised a <protein>monoclonal antibody</protein> to document expression and biochemistry of the <protein>human TCF-1 protein</protein> .


As expected , the TCF-1 protein was detectable only in cell lines of T lineage .

As expected , the <protein>TCF-1 protein</protein> was detectable only in <cell_line>cell lines of T lineage</cell_line> .


Its expression was always restricted to the nucleus .


Immunohistochemistry on a panel of human tissues revealed that the TCF-1 protein was found exclusively in thymocytes and in CD3+ T cells in peripheral lymphoid tissues .

Immunohistochemistry on a panel of human tissues revealed that the <protein>TCF-1 protein</protein> was found exclusively in thymocytes and in <cell_line>CD3+ T cells</cell_line> in peripheral lymphoid tissues .


Western blotting yielded a set of bands ranging from 25 kD to 55 kD , resulting from extensive alternative splicing .


The TCF-1 protein was detectable in all samples of a set of 22 T-cell malignancies of various stages of maturation , but was absent from a large number of other hematologic neoplasms .

The <protein>TCF-1</protein> protein was detectable in all samples of a set of 22 <cell_type>T-cell malignancies</cell_type> of various stages of maturation , but was absent from a large number of other <cell_type>hematologic neoplasms</cell_type> .


These observations imply a T cell-specific function for TCF-1 , a notion corroborated by recent observations on Tcf-1 knock-out mice .

These observations imply a T cell-specific function for <protein>TCF-1</protein> , a notion corroborated by recent observations on Tcf-1 knock-out mice .


In addition , these results indicate that nuclear TCF-1 expression can serve as a pan-T-lineage marker in the diagnosis of lymphoid malignancies .

In addition , these results indicate that nuclear <protein>TCF-1</protein> expression can serve as a pan-T-lineage marker in the diagnosis of lymphoid malignancies .


Cross-linking of Fc gamma receptors activates HIV-1 long terminal repeat -driven transcription in human monocytes .

Cross-linking of <protein>Fc gamma receptors</protein> activates <dna>HIV-1 long terminal repeat</dna> -driven transcription in <cell_type>human monocytes</cell_type> .


Elevation of the levels of circulating immune complexes frequently accompanies HIV-1 infection and is a prognostic indicator of clinical progression from asymptomatic infection to AIDS .

Elevation of the levels of <protein>circulating immune complexes</protein> frequently accompanies HIV-1 infection and is a prognostic indicator of clinical progression from asymptomatic infection to AIDS .


Here we report that cross-linking of Fc gamma RI or Fc gamma RII by adherent human IgG or by specific anti-Fc gamma R mAb activates HIV-1 gene expression in the human monocytic cell line BF24 and increased HIV RNA expression in monocytes from HIV infected patients as assayed by reverse transcription-PCR .

Here we report that cross-linking of <protein>Fc gamma RI</protein> or <protein>Fc gamma RII</protein> by <protein>adherent human IgG</protein> or by specific <protein>anti-Fc gamma R mAb</protein> activates HIV-1 gene expression in the <cell_line>human monocytic cell line</cell_line> <cell_line>BF24</cell_line> and increased <rna>HIV RNA</rna> expression in <cell_type>monocytes</cell_type> from HIV infected patients as assayed by reverse transcription-PCR .


In THP-1 cells , Fc gamma R cross-linking induced NF-kappa B , which is known to bind to the regulatory region of the long terminal repeat ( LTR ) of HIV-1 and to activate HIV-1 transcription . Anti-TNF-alpha antibody but not anti-IL-1 beta antibody strongly inhibited both the induction of HIV-1- LTR -driven transcription and the induction of NF-kappa B by Fc gamma R cross-linking .

In <cell_line>THP-1 cells</cell_line> , <protein>Fc gamma R</protein> cross-linking induced <protein>NF-kappa B</protein> , which is known to bind to the <dna>regulatory region</dna> of the <dna>long terminal repeat</dna> ( <dna>LTR</dna> ) of HIV-1 and to activate HIV-1 transcription . <protein>Anti-TNF-alpha antibody</protein> but not <protein>anti-IL-1 beta antibody</protein> strongly inhibited both the induction of HIV-1- <dna>LTR</dna> -driven transcription and the induction of <protein>NF-kappa B</protein> by <protein>Fc gamma R</protein> cross-linking .


These results indicate that Fc gamma R can mediate a TNF-alpha -dependent induction of HIV-1 gene transcription and suggest that immune complexes may contribute to the pathophysiology of HIV-1 infection by augmenting viral replication in monocytes .

These results indicate that <protein>Fc gamma R</protein> can mediate a <protein>TNF-alpha</protein> -dependent induction of <dna>HIV-1 gene</dna> transcription and suggest that <protein>immune complexes</protein> may contribute to the pathophysiology of HIV-1 infection by augmenting viral replication in <cell_type>monocytes</cell_type> .


Signalling via CD28 of human naive neonatal T lymphocytes .

Signalling via <protein>CD28</protein> of <cell_line>human naive neonatal T lymphocytes</cell_line> .


Accessory molecules play a crucial role in the development of the T cell response to antigenic challenge .


We have examined the role of CD28 in modulating the 'naive ' neonatal T cell response to anti-CD2 -mediated activation .

We have examined the role of <protein>CD28</protein> in modulating the 'naive ' neonatal T cell response to <protein>anti-CD2</protein> -mediated activation .


To compare the role of CD28 , neonatal and adult T cells were stimulated with a pair of mitogenic anti-CD2 antibodies in the presence or absence of anti-CD28 MoAb .

To compare the role of <protein>CD28</protein> , <cell_type>neonatal</cell_type> and <cell_type>adult T cells</cell_type> were stimulated with a pair of <protein>mitogenic anti-CD2 antibodies</protein> in the presence or absence of <protein>anti-CD28 MoAb</protein> .


With anti-CD2 alone , neonatal T cells proliferated slightly but produced no detectable IL-2 , whereas adult T cells proliferated vigorously , with significant IL-2 production .

With <protein>anti-CD2</protein> alone , <cell_type>neonatal T cells</cell_type> proliferated slightly but produced no detectable <protein>IL-2</protein> , whereas adult <cell_type>T cells</cell_type> proliferated vigorously , with significant <protein>IL-2</protein> production .


Costimulation with anti-CD28 MoAb greatly enhanced the proliferative response of neonatal T cells to levels equivalent to those of adult T cells , whereas adult T cells showed only slight increases .

Costimulation with <protein>anti-CD28 MoAb</protein> greatly enhanced the proliferative response of <cell_type>neonatal T cells</cell_type> to levels equivalent to those of <cell_type>adult T cells</cell_type> , whereas <cell_type>adult T cells</cell_type> showed only slight increases .


Although IL-2 secretion was increased in the presence of anti-CD28 MoAb , neonatal T cell IL-2 production remained lower than in adults .

Although <protein>IL-2</protein> secretion was increased in the presence of <protein>anti-CD28 MoAb</protein> , <cell_type>neonatal T cell</cell_type> <protein>IL-2</protein> production remained lower than in adults .


In contrast , enhancement of IL-2 mRNA expression in neonates was similar to adult levels .

In contrast , enhancement of <rna>IL-2 mRNA</rna> expression in neonates was similar to adult levels .


Anti- CD28 MoAb costimulation increased NF kappa B levels in neonates , albeit to levels lower than that of adults .

Anti- <protein>CD28 MoAb</protein> costimulation increased <protein>NF kappa B</protein> levels in neonates , albeit to levels lower than that of adults .


The cellular mechanism governing the diminished proliferative response of neonatal T lymphocytes to anti-CD2 may therefore be due to decreased NF kappa B induction , reduced IL-2 mRNA expression and deficient IL-2 production .

The cellular mechanism governing the diminished proliferative response of <cell_type>neonatal T lymphocytes</cell_type> to <protein>anti-CD2</protein> may therefore be due to decreased <protein>NF kappa B</protein> induction , reduced <rna>IL-2 mRNA</rna> expression and deficient <protein>IL-2</protein> production .


Although anti-CD28 MoAb costimulation enhances all of the above signals , NF kappa B and IL-2 levels remain lower than in adults , suggesting the need for further activation requirements in the neonate .

Although <protein>anti-CD28 MoAb</protein> costimulation enhances all of the above signals , NF kappa B and IL-2 levels remain lower than in adults , suggesting the need for further activation requirements in the neonate .


TCL1 oncogene activation in preleukemic T cells from a case of ataxia-telangiectasia .

TCL1 oncogene activation in <cell_type>preleukemic T cells</cell_type> from a case of ataxia-telangiectasia .


The TCL1 oncogene on human chromosome 14q32.1 is involved in chromosome translocations [ t ( 14 ; 14 ) ( q11 ; q32.1 ) and t ( 7 ; 14 ) ( q35 ; q32.1 ) ] and inversions [ inv14 ( q11 ; q32.1 ) ] with TCR alpha/beta loci in T-cell leukemias , such as T-prolymphocytic ( T-PLL ) .

The <dna>TCL1 oncogene</dna> on <dna>human chromosome</dna> <dna>14q32.1</dna> is involved in chromosome translocations [ <dna>t ( 14 ; 14 ) ( q11 ; q32.1 )</dna> and <dna>t ( 7 ; 14 ) ( q35 ; q32.1 )</dna> ] and inversions [ <dna>inv14 ( q11 ; q32.1 )</dna> ] with <dna>TCR alpha/beta loci</dna> in T-cell leukemias , such as T-prolymphocytic ( T-PLL ) .


It is also involved in T- acute and- chronic leukemias arising in cases of ataxia-telangiectasia ( AT ) , an immunodeficiency syndrome .


Similar chromosomal rearrangements occur also in the clonally expanded T cells in AT patients before the appearance of the overt leukemia .

Similar chromosomal rearrangements occur also in the clonally expanded <cell_type>T cells</cell_type> in AT patients before the appearance of the overt leukemia .


We have analyzed the expression of TCL1 mRNA and protein in peripheral blood lymphocytes ( PBLs ) from four AT cases and from healthy controls .

We have analyzed the expression of <rna>TCL1 mRNA</rna> and <protein>protein</protein> in <cell_type>peripheral blood lymphocytes</cell_type> ( <cell_type>PBLs</cell_type> ) from four AT cases and from healthy controls .


We found that the TCL1 gene was overexpressed in the PBLs of an AT patient with a large clonal T-cell population exhibiting the t ( 14 ; 14 ) translocation but not in the lymphocytes of the other cases .

We found that the <dna>TCL1 gene</dna> was overexpressed in the <cell_type>PBLs</cell_type> of an AT patient with a <cell_line>large clonal T-cell population</cell_line> exhibiting the t ( 14 ; 14 ) translocation but not in the <cell_type>lymphocytes</cell_type> of the other cases .


Fluorescence in situ hybridization of the TCL1 genomic locus to lymphocyte metaphases from the AT patient with the T-cell clonal expansion showed that the breakpoint of the t ( 14 ; 14 ) translocation lies within the TCL1 locus and is accompanied by an inverted duplication of the distal part of chromosome 14 .

Fluorescence in situ hybridization of the <dna>TCL1 genomic locus</dna> to lymphocyte metaphases from the AT patient with the T-cell clonal expansion showed that the breakpoint of the t ( 14 ; 14 ) translocation lies within the <dna>TCL1 locus</dna> and is accompanied by an inverted duplication of the <dna>distal part</dna> of <dna>chromosome 14</dna> .


These data indicate that TCL1 is activated in preleukemic clonal cells as a consequence of chromosome translocation involving sequences from the TCR locus at 14q11 .

These data indicate that <dna>TCL1</dna> is activated in <cell_line>preleukemic clonal cells</cell_line> as a consequence of chromosome translocation involving sequences from the <dna>TCR locus</dna> at <dna>14q11</dna> .


Deregulation of TCL1 is the first event in the initiation of malignancy in these types of leukemias and represents a potential tool for clinical evaluation .

Deregulation of <dna>TCL1</dna> is the first event in the initiation of malignancy in these types of leukemias and represents a potential tool for clinical evaluation .


C/EBP proteins activate transcription from the human immunodeficiency virus type 1 long terminal repeat in macrophages/ monocytes .

<protein>C/EBP proteins</protein> activate transcription from the <dna>human immunodeficiency virus type 1 long terminal repeat</dna> in macrophages/ <cell_type>monocytes</cell_type> .


Three binding sites for C/EBP proteins are found in the human immunodeficiency virus type 1 ( HIV-1 ) long terminal repeat ( LTR ) ( V.M. Tesmer , A.Rajadhyaksha , J.Babin , and M.Bina , Proc.Natl.Acad.Sci. USA 90 : 7298-7302 , 1993 ) .

Three binding sites for <protein>C/EBP proteins</protein> are found in the <dna>human immunodeficiency virus type 1 ( HIV-1 ) long terminal repeat</dna> ( <dna>LTR</dna> ) ( V.M. Tesmer , A.Rajadhyaksha , J.Babin , and M.Bina , Proc.Natl.Acad.Sci. USA 90 : 7298-7302 , 1993 ) .


We have determined the functional role of C/EBP proteins and C/EBP sites in regulating transcription from the HIV- 1 LTR in monocytes/macrophages .

We have determined the functional role of <protein>C/EBP proteins</protein> and <dna>C/EBP sites</dna> in regulating transcription from the <dna>HIV- 1 LTR</dna> in <cell_type>monocytes/macrophages</cell_type> .


Inhibition of endogenous C/EBP proteins , using either an excess of C/EBP binding sites or a trans- dominant negative inhibitor , demonstrated that C/EBP proteins are required for basal and activated levels of HIV-1 LTR transcription in the promonocytic cell line U937 .

Inhibition of <protein>endogenous C/EBP proteins</protein> , using either an excess of <dna>C/EBP binding sites</dna> or a <dna>trans- dominant negative inhibitor</dna> , demonstrated that <protein>C/EBP proteins</protein> are required for basal and activated levels of <dna>HIV-1 LTR</dna> transcription in the <cell_line>promonocytic cell line U937</cell_line> .


Northern ( RNA ) blots and binding assays showed that NF-IL6 is the only known C/EBP family member which is increased when U937 cells are activated .

Northern ( RNA ) blots and binding assays showed that <protein>NF-IL6</protein> is the only known <protein>C/EBP family member</protein> which is increased when <cell_line>U937 cells</cell_line> are activated .


Mutational analyses of the HIV-1 LTR showed that one C/EBP site is required for normal LTR transcription both before and after cellular activation and that the two 3 ' C/EBP sites are functionally equivalent .

Mutational analyses of the <dna>HIV-1 LTR</dna> showed that one <dna>C/EBP site</dna> is required for normal <dna>LTR</dna> transcription both before and after cellular activation and that the two 3 ' <dna>C/EBP sites</dna> are functionally equivalent .


However , transcription from crippled HIV-1 LTRs lacking C/EBP sites can still be induced following activation of U937 cells .

However , transcription from <dna>crippled HIV-1 LTRs</dna> lacking <dna>C/EBP sites</dna> can still be induced following activation of <cell_line>U937 cells</cell_line> .


Several models are suggested for how elevated NF-IL6 may participate in an autostimulatory loop involving HIV infection , macrophage activation , cytokine expression , and HIV replication .

Several models are suggested for how elevated <protein>NF-IL6</protein> may participate in an autostimulatory loop involving HIV infection , macrophage activation , <protein>cytokine</protein> expression , and HIV replication .


Human immunodeficiency virus type-2 gene expression : two enhancers and their activation by T-cell activators .

Human immunodeficiency virus type-2 gene expression : two <dna>enhancers</dna> and their activation by <cell_type>T-cell</cell_type> activators .


The human immunodeficiency viruses ( HIVs ) may include a spectrum of retroviruses with varying potential to infect their host , undergo long periods of latent infection , and induce pathology .


Since expression of the viruses is in large part regulated by the sequence elements in their long terminal repeats ( LTRs ) , this study was directed to an analysis of the regulatory elements in the HIV-2 LTR .

Since expression of the viruses is in large part regulated by the <dna>sequence elements</dna> in their <dna>long terminal repeats</dna> ( <dna>LTRs</dna> ) , this study was directed to an analysis of the <dna>regulatory elements</dna> in the <dna>HIV-2 LTR</dna> .


The HIV-2 LTR was found to contain two enhancers .

The <dna>HIV-2 LTR</dna> was found to contain two <dna>enhancers</dna> .


One of these enhancers is , in part , identical to the HIV-1 enhancer .

One of these <dna>enhancers</dna> is , in part , identical to the <dna>HIV-1 enhancer</dna> .


This enhancer in HIV-1 is the T-cell activation response element ; in HIV-2 , however , it is the second enhancer that is mainly responsible for activation in response to T-cell activators .

This <dna>enhancer</dna> in HIV-1 is the <dna>T-cell activation response element</dna> ; in HIV-2 , however , it is the <dna>second enhancer</dna> that is mainly responsible for activation in response to T-cell activators .


The second enhancer interacts with two nuclear binding proteins ( 85 kD and 27 kD mobility ) that appear to be required for optimal enhancer function and activation .

The second <dna>enhancer</dna> interacts with two <protein>nuclear binding proteins</protein> ( 85 kD and 27 kD mobility ) that appear to be required for optimal enhancer function and activation .


Observations such as these encourage the speculation that there may be subtle differences in the regulation of HIV-1 and HIV-2 expression that may be relevant to the possible longer latency and reduced pathogenicity of HIV-2 .


NF-M ( chicken C/EBP beta ) induces eosinophilic differentiation and apoptosis in a hematopoietic progenitor cell line .

<protein>NF-M</protein> ( <protein>chicken C/EBP beta</protein> ) induces eosinophilic differentiation and apoptosis in a <cell_line>hematopoietic progenitor cell line</cell_line> .


CAAT/enhancer binding proteins ( C/EBPs ) are transcriptional activators implicated in the differentiation processes of various cell lineages .

<protein>CAAT/enhancer binding proteins</protein> ( <protein>C/EBPs</protein> ) are transcriptional activators implicated in the differentiation processes of various cell lineages .


We have shown earlier that NF-M , the chicken homolog of C/EBP beta , is specifically expressed in myelomonocytic and eosinophilic cells of the hematopoietic system .

We have shown earlier that <protein>NF-M</protein> , the <protein>chicken homolog</protein> of <protein>C/EBP beta</protein> , is specifically expressed in <cell_type>myelomonocytic and eosinophilic cells</cell_type> of the hematopoietic system .


To investigate the role of NF-M in hematopoietic cell lineage commitment , we constructed a conditional form of the protein by fusing it to the hormone binding domain of the human estrogen receptor .

To investigate the role of <protein>NF-M</protein> in <cell_line>hematopoietic cell lineage</cell_line> commitment , we constructed a conditional form of the protein by fusing it to the <protein>hormone binding domain</protein> of the <protein>human estrogen receptor</protein> .


This construct was stably expressed in a multipotent progenitor cell line transformed by the Myb-Ets oncoprotein .

This construct was stably expressed in a <cell_line>multipotent progenitor cell line</cell_line> transformed by the <protein>Myb-Ets oncoprotein</protein> .


We report here that both NF-M-dependent promoter constructs and resident genes could be activated by addition of beta-estradiol to the NF-M-estrogen receptor expressing progenitors .

We report here that both <dna>NF-M-dependent promoter constructs</dna> and resident genes could be activated by addition of beta-estradiol to the <cell_line>NF-M-estrogen receptor expressing progenitors</cell_line> .


At the same time , we observed a down-regulation of progenitor-specific surface markers and the up-regulation of differentiation markers restricted to the eosinophil and myeloid lineages .

At the same time , we observed a down-regulation of <protein>progenitor-specific surface markers</protein> and the up-regulation of <protein>differentiation markers</protein> restricted to the <cell_type>eosinophil</cell_type> and <cell_type>myeloid lineages</cell_type> .


In addition to the onset of differentiation , cell death was induced with typical apoptotic features .


Our results suggest that NF-M plays an important role in commitment along the eosinophil lineage and in the induction of apoptosis .

Our results suggest that <protein>NF-M</protein> plays an important role in commitment along the <cell_type>eosinophil lineage</cell_type> and in the induction of apoptosis .


Prolactin and interleukin-2 receptors in T lymphocytes signal through a MGF-STAT5-like transcription factor .

<protein>Prolactin</protein> and <protein>interleukin-2 receptors</protein> in <cell_type>T lymphocytes</cell_type> signal through a <protein>MGF-STAT5-like transcription factor</protein> .


The cell surface receptors for PRL and interleukin-2 ( IL-2 ) are structurally distinct , but share regulatory tasks in T lymphocytes .

The cell surface receptors for <protein>PRL</protein> and <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) are structurally distinct , but share regulatory tasks in <cell_type>T lymphocytes</cell_type> .


They can stimulate proliferation and activate transcription of over-lapping sets of genes of T cells .

They can stimulate proliferation and activate transcription of over-lapping sets of genes of <cell_type>T cells</cell_type> .


PRL and IL-2 receptor activation are both linked to the Jak/Stat ( signal transducer and activator of transcription ) pathway .

<protein>PRL</protein> and <protein>IL-2</protein> receptor activation are both linked to the <protein>Jak/Stat</protein> ( <protein>signal transducer and activator of transcription</protein> ) pathway .


We investigated the ability of PRL and IL-2 to activate Stat proteins in different T cell lines .

We investigated the ability of <protein>PRL</protein> and <protein>IL-2</protein> to activate <protein>Stat proteins</protein> in different <cell_line>T cell lines</cell_line> .


The DNA binding specificities , the reactivities toward Stat-specific antisera , and the mol wt of IL-2 -and PRL-induced DNA-binding proteins in Nb2 and C196 T cell lines were investigated .

The DNA binding specificities , the reactivities toward Stat-specific antisera , and the mol wt of <protein>IL-2</protein> -and <protein>PRL-induced DNA-binding proteins</protein> in <cell_line>Nb2 and C196 T cell lines</cell_line> were investigated .


A comparison with the Stat proteins induced by interferon-gamma , PRL , and IL-6 in T47D mammary tumor cells was made .

A comparison with the <protein>Stat proteins</protein> induced by <protein>interferon-gamma</protein> , <protein>PRL</protein> , and <protein>IL-6</protein> in <cell_line>T47D mammary tumor cells</cell_line> was made .


We found that these parameters were indistinguishable for one of the PRL- and IL-2-induced factors .

We found that these parameters were indistinguishable for one of the <protein>PRL- and IL-2-induced factors</protein> .


A transcription factor closely related to mammary gland factor-Stat5 is rapidly activated upon interaction of IL-2 and PRL with their respective receptors .

A transcription factor closely related to <protein>mammary gland factor-Stat5</protein> is rapidly activated upon interaction of <protein>IL-2</protein> and <protein>PRL</protein> with their respective receptors .


Activation of a second protein related to Stat1 was also observed .

Activation of a second protein related to <protein>Stat1</protein> was also observed .


Our results emphasize the role of PRL as a regulator of the immune response and indicate that the Stat factors mammary gland factor-Stat5 and Stat1 play a role in the regulation of gene expression during T cell development .

Our results emphasize the role of <protein>PRL</protein> as a regulator of the immune response and indicate that the <protein>Stat factors</protein> <protein>mammary gland factor-Stat5</protein> and <protein>Stat1</protein> play a role in the regulation of gene expression during T cell development .


ETS1 transactivates the human GM-CSF promoter in Jurkat T cells stimulated with PMA and ionomycin .

<protein>ETS1</protein> transactivates the <dna>human GM-CSF promoter</dna> in <cell_line>Jurkat T cells</cell_line> stimulated with PMA and ionomycin .


Activation of T helper cells results in coordinate expression of a number of cytokines involved in differentiation , proliferation and activation of the haematopoietic system .

Activation of <cell_type>T helper cells</cell_type> results in coordinate expression of a number of <protein>cytokines</protein> involved in differentiation , proliferation and activation of the haematopoietic system .


Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) is one such cytokine whose increased expression results partly from increases in transcription .

<protein>Granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) is one such <protein>cytokine</protein> whose increased expression results partly from increases in transcription .


Cis-acting elements with NF kappa B , AP-1 and ETS-like motifs have been identified in the promoter region of the GM-CSF gene , which are important for transcriptional activity following PMA and ionomycin stimulation .

<dna>Cis-acting elements</dna> with <protein>NF kappa B</protein> , <protein>AP-1</protein> and <dna>ETS-like motifs</dna> have been identified in the promoter region of the <dna>GM-CSF gene</dna> , which are important for transcriptional activity following PMA and ionomycin stimulation .


A number of the ETS family of transcription factors are expressed in T cells , including ETS1 and ELF1 .

A number of the <protein>ETS family</protein> of <protein>transcription factors</protein> are expressed in <cell_type>T cells</cell_type> , including <protein>ETS1</protein> and <protein>ELF1</protein> .


Here we describe the ability of these factors to interact with a site ( GM5 ) , located within the CLE0 element , -47 to -40 upstream of the GM-CSF transcription initiation site .

Here we describe the ability of these factors to interact with a site ( <dna>GM5</dna> ) , located within the <dna>CLE0 element</dna> , <dna>-47 to -40 upstream</dna> of the <dna>GM-CSF transcription initiation site</dna> .


Exogenous ETS1 , but not ELF1 , can transactivate GM-CSF , through the GM5 site , in a PMA/ionomycin dependent manner .

Exogenous <protein>ETS1</protein> , but not <protein>ELF1</protein> , can transactivate <protein>GM-CSF</protein> , through the <dna>GM5</dna> site , in a PMA/ionomycin dependent manner .


Other unidentified ETS-like factors present in Jurkat cells are also capable of binding GM5 .

Other unidentified <protein>ETS-like factors</protein> present in <cell_line>Jurkat cells</cell_line> are also capable of binding <dna>GM5</dna> .


Mutation of the core ETS binding site from -GGAA- to -GGAT- prevents the binding of ETS-like factors with the exception of ETS1 .

Mutation of the core <dna>ETS binding site</dna> from <dna>-GGAA- to -GGAT-</dna> prevents the binding of <protein>ETS-like factors</protein> with the exception of <protein>ETS1</protein> .


The GM-CSF promoter , modified in this way to be ETS1 specific , is fully responsive to PMA/ionomycin induction , in addition to ETS1 transactivation in the presence of PMA and ionomycin .

The <dna>GM-CSF promoter</dna> , modified in this way to be <protein>ETS1</protein> specific , is fully responsive to PMA/ionomycin induction , in addition to <protein>ETS1</protein> transactivation in the presence of PMA and ionomycin .


Together these data suggest that ETS1 may be involved in mediating the increased GM-CSF production associated with T cell activation .

Together these data suggest that <protein>ETS1</protein> may be involved in mediating the increased <protein>GM-CSF</protein> production associated with <cell_type>T cell</cell_type> activation .


Quantitation of beta 1 triiodothyronine receptor mRNA in human tissues by competitive reverse transcription polymerase chain reaction .

Quantitation of <rna>beta 1 triiodothyronine receptor mRNA</rna> in human tissues by competitive reverse transcription polymerase chain reaction .


Thyroid hormones act by binding to nuclear receptor proteins , the thyroid hormone receptors ( TR ) alpha and beta .

Thyroid hormones act by binding to <protein>nuclear receptor proteins</protein> , the <protein>thyroid hormone receptors ( TR ) alpha and beta</protein> .


Data from cell culture and animal studies indicate that TR expression may be regulated to modulate target organ responsiveness to thyroid hormone .

Data from cell culture and animal studies indicate that <protein>TR</protein> expression may be regulated to modulate target organ responsiveness to thyroid hormone .