NFAT-1 activity had previously been thought to be confined to activated T-lymphocytes upon release of intracellular calcium .

<protein>NFAT-1</protein> activity had previously been thought to be confined to <cell_type>activated T-lymphocytes</cell_type> upon release of <cell_type>intracellular calcium</cell_type> .


By targeting NFAT-1 -dependent gene expression in transgenic mice we discovered new sites of NFAT-1 activity .

By targeting <protein>NFAT-1</protein> -dependent gene expression in transgenic mice we discovered new sites of <protein>NFAT-1</protein> activity .


Besides in T-lymphocytes NFAT-1 activity could also be induced in T-lymphocyte-depleted spleen cells and purified B-lymphocytes and requires agents that both release intracellular calcium and activate protein kinase C .

Besides in <cell_type>T-lymphocytes</cell_type> <protein>NFAT-1</protein> activity could also be induced in <cell_type>T-lymphocyte-depleted spleen cells</cell_type> and <cell_type>purified B-lymphocytes</cell_type> and requires agents that both release intracellular calcium and activate <protein>protein kinase C</protein> .


A difference in the time course of appearance of NFAT-1 activity between T-lymphocytes and non-T-lymphocytes was revealed .

A difference in the time course of appearance of <protein>NFAT-1</protein> activity between <cell_type>T-lymphocytes</cell_type> and <cell_type>non-T-lymphocytes</cell_type> was revealed .


Constitutive expression was observed in a small population of cells in the dermis and some mice have developed skin lesions .


Interestingly , the tissue pattern of expression of the NFAT-1 activity resembles the expression pattern described for HIV-LTR/tat transgenic mice ( Vogel , J. , Hinrichs , S. H. , Reynolds , R. K. , Luciw , P. A. , and Jay , G. ( 1988 ) Nature 335 , 606-611 ) .

Interestingly , the tissue pattern of expression of the <protein>NFAT-1</protein> activity resembles the expression pattern described for HIV-LTR/tat transgenic mice ( Vogel , J. , Hinrichs , S. H. , Reynolds , R. K. , Luciw , P. A. , and Jay , G. ( 1988 ) Nature 335 , 606-611 ) .


This similarity in expression and the fact that NFAT-1 has been shown to bind functional sequences in HIV-LTR suggest a role for NFAT-1 in dermal activation of the HIV-LTR .

This similarity in expression and the fact that <protein>NFAT-1</protein> has been shown to bind <dna>functional sequences</dna> in <dna>HIV-LTR</dna> suggest a role for <protein>NFAT-1</protein> in dermal activation of the <dna>HIV-LTR</dna> .


A novel T-cell protein which recognizes a palindromic sequence in the negative regulatory element of the human immunodeficiency virus long terminal repeat .

A novel <protein>T-cell protein</protein> which recognizes a <dna>palindromic sequence</dna> in the <dna>negative regulatory element</dna> of the <dna>human immunodeficiency virus long terminal repeat</dna> .


Two major protein-binding sites within the negative regulatory element of the human immunodeficiency virus type 1 long terminal repeat have been identified .

Two <dna>major protein-binding sites</dna> within the <dna>negative regulatory element</dna> of the <dna>human immunodeficiency virus type 1 long terminal repeat</dna> have been identified .


One ( site B ) contained a palindromic sequence with homology to steroid/thyroid hormone response elements but was distinct from previously described binding sites of this class .

One ( <dna>site B</dna> ) contained a <dna>palindromic sequence</dna> with homology to <dna>steroid/thyroid hormone response elements</dna> but was distinct from previously described binding sites of this class .


A novel T-cell protein recognized the palindromic sequence within site B and also bound estrogen- or thyroid hormone-response elements with lower affinity .

A novel <protein>T-cell protein</protein> recognized the <dna>palindromic sequence</dna> within <dna>site B</dna> and also bound <dna>estrogen- or thyroid hormone-response elements</dna> with lower affinity .


A 7-base-pair mutation in the site B palindrome , which destroyed protein binding , resulted in increased expression from the human immunodeficiency virus type 1 long terminal repeat in T cells .

A 7-base-pair mutation in the <dna>site B palindrome</dna> , which destroyed protein binding , resulted in increased expression from the <dna>human immunodeficiency virus type 1 long terminal repeat</dna> in <cell_type>T cells</cell_type> .


Progesterone suppression of pregnancy lymphocytes is not mediated by glucocorticoid effect .

Progesterone suppression of <cell_type>pregnancy lymphocytes</cell_type> is not mediated by glucocorticoid effect .


This study investigated whether the suppressive effect of progesterone on pregnancy lymphocytes is mediated by specific progesterone receptors .

This study investigated whether the suppressive effect of progesterone on <cell_type>pregnancy lymphocytes</cell_type> is mediated by specific <protein>progesterone receptors</protein> .


The effects of a competitive progesterone antagonist ( RU486 ) and a specific glucocorticoid receptor blocker ( RU43044 ) were tested on the release of a blocking factor by progesterone-treated pregnancy lymphocytes .

The effects of a competitive progesterone antagonist ( RU486 ) and a specific <protein>glucocorticoid receptor</protein> blocker ( RU43044 ) were tested on the release of a <protein>blocking factor</protein> by <cell_line>progesterone-treated pregnancy lymphocytes</cell_line> .


RU 486 tested at an equal concentration as progesterone significantly inhibited the production of the blocking factor , while RU 43044 was without effect .

RU 486 tested at an equal concentration as progesterone significantly inhibited the production of the <protein>blocking factor</protein> , while RU 43044 was without effect .


These data suggest that in pregnancy , lymphocyte progesterone acts on specific progesterone receptors and glucocorticoid binding sites are not involved .

These data suggest that in pregnancy , lymphocyte progesterone acts on specific <protein>progesterone receptors</protein> and <protein>glucocorticoid binding sites</protein> are not involved .


The 56-59-kilodalton protein identified in untransformed steroid receptor complexes is a unique protein that exists in cytosol in a complex with both the 70- and 90-kilodalton heat shock proteins .

The <protein>56-59-kilodalton protein</protein> identified in <protein>untransformed steroid receptor complexes</protein> is a <protein>unique protein</protein> that exists in cytosol in a complex with both the <protein>70- and 90-kilodalton heat shock proteins</protein> .


It has previously been shown that 9S , untransformed progestin , estrogen , androgen , and glucocorticoid receptor complexes in rabbit uterine and liver cytosols contain a 59-kDa protein [ Tai , P.K. , Maeda , Y. , Nakao , K. , Wakim , N.G. , Duhring , J.L. , & Faber , L.E. ( 1986 ) Biochemistry 25 , 5269-5275 ] .

It has previously been shown that <protein>9S</protein> , <protein>untransformed progestin , estrogen , androgen , and glucocorticoid receptor complexes</protein> in rabbit uterine and liver cytosols contain a <protein>59-kDa protein</protein> [ Tai , P.K. , Maeda , Y. , Nakao , K. , Wakim , N.G. , Duhring , J.L. , & Faber , L.E. ( 1986 ) Biochemistry 25 , 5269-5275 ] .


In this work we show that the monoclonal antibody KN 382/EC1 raised against the rabbit 59-kDa protein reacts with 9S , untransformed glucocorticoid receptor complexes in cytosol prepared from human IM-9 lymphocytes but not with 4S salt-transformed receptors .

In this work we show that the <protein>monoclonal antibody KN 382/EC1</protein> raised against the <protein>rabbit 59-kDa protein</protein> reacts with <protein>9S</protein> , <protein>untransformed glucocorticoid receptor complexes</protein> in cytosol prepared from <cell_line>human IM-9 lymphocytes</cell_line> but not with <protein>4S salt-transformed receptors</protein> .


The human protein recognized by the EC1 antibody is a 56-kDa protein ( p56 ) of moderate abundance located predominantly in the cytoplasm by indirect immunofluorescence .

The human protein recognized by the <protein>EC1 antibody</protein> is a <protein>56-kDa protein</protein> ( <protein>p56</protein> ) of moderate abundance located predominantly in the cytoplasm by indirect immunofluorescence .


There are at least six isomorphs of p56 by two-dimensional gel analysis .

There are at least six <protein>isomorphs</protein> of <protein>p56</protein> by two-dimensional gel analysis .


N-Terminal sequencing ( 20 amino acids ) shows that p56 is a unique human protein .

N-Terminal sequencing ( 20 amino acids ) shows that <protein>p56</protein> is a <protein>unique human protein</protein> .


When p56 is immunoadsorbed from IM-9 cell cytosol , both the 70- and 90-kDa heat shock proteins are coadsorbed in an immune-specific manner .

When <protein>p56</protein> is immunoadsorbed from <cell_line>IM-9 cell</cell_line> cytosol , both the <protein>70- and 90-kDa heat shock proteins</protein> are coadsorbed in an immune-specific manner .


Neither heat shock protein reacts directly with the EC1 antibody .

Neither <protein>heat shock protein</protein> reacts directly with the <protein>EC1 antibody</protein> .


We conclude that p56 exists in cytosol in a higher order complex containing hsp70 and hsp90 , both of which in turn have been found to be associated with untransformed steroid receptors .

We conclude that <protein>p56</protein> exists in cytosol in a higher order complex containing <protein>hsp70</protein> and <protein>hsp90</protein> , both of which in turn have been found to be associated with <protein>untransformed steroid receptors</protein> .


Sequence-specific DNA binding of the proto-oncoprotein ets-1 defines a transcriptional activator sequence within the long terminal repeat of the Moloney murine sarcoma virus .

Sequence-specific DNA binding of the <protein>proto-oncoprotein</protein> <protein>ets-1</protein> defines a <dna>transcriptional activator sequence</dna> within the <dna>long terminal repeat</dna> of the Moloney murine sarcoma virus .


The ets proto-oncogene family is a group of sequence-related genes whose normal cellular function is unknown .

The <dna>ets proto-oncogene family</dna> is a group of <dna>sequence-related genes</dna> whose normal cellular function is unknown .


In a study of cellular proteins involved in the transcriptional regulation of murine retroviruses in T lymphocytes , we have discovered that a member of the ets gene family encodes a sequence-specific DNA-binding protein .

In a study of <protein>cellular proteins</protein> involved in the transcriptional regulation of murine retroviruses in <cell_type>T lymphocytes</cell_type> , we have discovered that a member of the <dna>ets gene family</dna> encodes a <protein>sequence-specific DNA-binding protein</protein> .


A mouse ets-1 cDNA clone was obtained by screening a mouse thymus cDNA expression library with a double-stranded oligonucleotide probe representing 20 bp of the Moloney murine sarcoma virus ( MSV ) long terminal repeat ( LTR ) .

A <dna>mouse ets-1 cDNA clone</dna> was obtained by screening a mouse thymus cDNA expression library with a <dna>double-stranded oligonucleotide probe</dna> representing 20 bp of the Moloney murine sarcoma virus ( MSV ) <dna>long terminal repeat</dna> ( <dna>LTR</dna> ) .


The cDNA sequence has an 813-bp open reading frame ( ORF ) whose predicted amino acid sequence is 97.6 % identical to the 272 carboxy-terminal amino acids of the human ets-1 protein .

The <dna>cDNA sequence</dna> has an <dna>813-bp open reading frame</dna> ( <dna>ORF</dna> ) whose predicted amino acid sequence is 97.6 % identical to the <protein>272 carboxy-terminal amino acids</protein> of the <protein>human ets-1 protein</protein> .


The ORF was expressed in bacteria , and the 30-kD protein product was shown to bind DNA in a sequence-specific manner by mobility-shift assays , Southwestern blot analysis , and methylation interference .

The <dna>ORF</dna> was expressed in bacteria , and the <protein>30-kD protein product</protein> was shown to bind DNA in a sequence-specific manner by mobility-shift assays , Southwestern blot analysis , and methylation interference .


A mutant LTR containing four base pair substitutions in the ets-1 binding site was constructed and was shown to have reduced binding in vitro .

A <dna>mutant LTR</dna> containing four base pair substitutions in the <dna>ets-1 binding site</dna> was constructed and was shown to have reduced binding in vitro .


Transcriptional efficiency of the MSV LTR promoter containing this disrupted ets-1 binding site was compared to the activity of a wild-type promoter in mouse T lymphocytes in culture , and 15- to 20-fold reduction in expression of a reporter gene was observed .

Transcriptional efficiency of the <dna>MSV LTR promoter</dna> containing this disrupted <dna>ets-1 binding site</dna> was compared to the activity of a <dna>wild-type promoter</dna> in <cell_type>mouse T lymphocytes</cell_type> in culture , and 15- to 20-fold reduction in expression of a <dna>reporter gene</dna> was observed .


We propose that ets-1 functions as a transcriptional activator of mammalian type-C retroviruses and speculate that ets-related genes constitute a new group of eukaryotic DNA-binding proteins .

We propose that <protein>ets-1</protein> functions as a transcriptional activator of mammalian type-C retroviruses and speculate that <dna>ets-related genes</dna> constitute a new group of <protein>eukaryotic DNA-binding proteins</protein> .


Type II estrogen binding sites in human peripheral blood mononuclear cells : variations during the menstrual cycle .

<protein>Type II estrogen binding sites</protein> in <cell_type>human peripheral blood mononuclear cells</cell_type> : variations during the menstrual cycle .


We have previously reported that human peripheral blood mononuclear cells ( PBMC ) contain type II estrogen binding sites ( type II EBS ) .

We have previously reported that <cell_type>human peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) contain type <protein>II estrogen binding sites</protein> ( <protein>type II EBS</protein> ) .


In this study , the fluctuations of type II EBS during the menstrual cycle were analyzed in 6 normally menstruating women .

In this study , the fluctuations of <protein>type II EBS</protein> during the menstrual cycle were analyzed in 6 normally menstruating women .


Approximately 3 times higher levels of type II EBS were found in the periovulatory period with respect to both follicular and luteal phases .

Approximately 3 times higher levels of <protein>type II EBS</protein> were found in the periovulatory period with respect to both follicular and luteal phases .


In postmenopausal women the mean type II EBS levels were similar to those observed in the follicular phase of the cycle .

In postmenopausal women the mean <protein>type II EBS</protein> levels were similar to those observed in the follicular phase of the cycle .


However , in 3 postmenopausal patients a short course of estrogen or tamoxifen resulted in a marked increase of type II EBS levels .

However , in 3 postmenopausal patients a short course of estrogen or tamoxifen resulted in a marked increase of <protein>type II EBS</protein> levels .


Tamoxifen was also found to compete with 17 beta-estradiol for type II EBS in PBMC , although to a lesser extent than diethylstilbestrol .

Tamoxifen was also found to compete with 17 beta-estradiol for <protein>type II EBS</protein> in <cell_type>PBMC</cell_type> , although to a lesser extent than diethylstilbestrol .


Mononuclear leukocyte glucocorticoid receptor binding characteristics and down-regulation in major depression .

<cell_type>Mononuclear leukocyte</cell_type> <protein>glucocorticoid receptor</protein> binding characteristics and down-regulation in major depression .


Some patients with major depressive disorder ( MDD ) have elevated plasma cortisol concentrations and show failure to suppress cortisol secretion upon administration of dexamethasone ( DEX ) , yet they do not have Cushingoid features .


To study whether this represents glucocorticoid ( GC ) resistance , [ 3H ] -DEX-binding assays were used to measure , in vitro , the GC receptor affinity ( 1/Kd ) and number ( Bmax ) in mononuclear leukocytes of 11 MDD patients and 15 control subjects .

To study whether this represents glucocorticoid ( GC ) resistance , [ 3H ] -DEX-binding assays were used to measure , in vitro , the <protein>GC receptor</protein> affinity ( 1/Kd ) and number ( Bmax ) in <cell_type>mononuclear leukocytes</cell_type> of 11 MDD patients and 15 control subjects .


No receptor abnormalities were detected in the MDD group ; thus any cellular defect leading to a lack of responsiveness to GC in the MDD patients , if present , probably lies beyond the initial receptor binding .


DEX ( 1.0 mg orally ) was administered to study in vivo GC receptor down-regulation .

DEX ( 1.0 mg orally ) was administered to study in <protein>vivo GC receptor</protein> down-regulation .


Compared to the control group , fewer depressed subjects down-regulated Bmax after DEX .


By paired t-test , Bmax decreased significantly in the control group but not in the depressed group .


Receptor number on the control day did not correlate significantly with the degree of receptor down-regulation , severity of depression or cortisol concentrations across all the subjects .


These results do not lend support to previous reports suggesting that GC resistance in MDD results from a GC receptor-binding abnormality , and they emphasize the importance of considering receptor studies in the context of GC-mediated cell processes in order to identify the exact cellular defect ( s ) leading to GC resistance .


Ras-related GTP-binding proteins and leukocyte signal transduction .

<protein>Ras-related GTP-binding proteins</protein> and <cell_type>leukocyte</cell_type> signal transduction .


Many aspects of leukocyte function are regulated by both heterotrimeric and Ras-related GTP-binding proteins , but there is little definite information about their roles in the specialized processes utilized by leukocytes for cell killing .

Many aspects of <cell_type>leukocyte</cell_type> function are regulated by both <protein>heterotrimeric</protein> and <protein>Ras-related GTP-binding proteins</protein> , but there is little definite information about their roles in the specialized processes utilized by <cell_type>leukocytes</cell_type> for cell killing .


Recent progress in understanding the regulation of the phagocyte NADPH oxidase by the Rac GTP-binding proteins provides a basis for defining the operational characteristics of one such phagocyte system .

Recent progress in understanding the regulation of the <protein>phagocyte NADPH oxidase</protein> by the <protein>Rac GTP-binding proteins</protein> provides a basis for defining the operational characteristics of one such phagocyte system .


It is clear from various studies that the activity of the NADPH oxidase can be modulated through the regulation of the GTP-GDP state of Rac .

It is clear from various studies that the activity of the <protein>NADPH oxidase</protein> can be modulated through the regulation of the GTP-GDP state of <protein>Rac</protein> .


Proteins exist in leukocytes able to modify GTP-binding protein function in this manner , and their activity may be regulated by signals generated on phagocyte stimulation .

Proteins exist in <cell_type>leukocytes</cell_type> able to modify <protein>GTP-binding protein</protein> function in this manner , and their activity may be regulated by signals generated on phagocyte stimulation .


Proteins of the Ras superfamily are likely to be involved in a variety of normal phagocyte functions through their ability to modulate the assembly of actin filaments , direct vesicle trafficking and fusion , and so forth .

Proteins of the <protein>Ras superfamily</protein> are likely to be involved in a variety of normal phagocyte functions through their ability to modulate the assembly of <protein>actin filaments</protein> , direct vesicle trafficking and fusion , and so forth .


BSAP : a key regulator of B-cell development and differentiation .

<protein>BSAP</protein> : a key regulator of <cell_type>B-cell</cell_type> development and differentiation .


B-cell-specific activator protein ( BSAP ) is a recently identified member of the Pax-gene family of transcription factors ; in the lymphoid system , BSAP is produced only in B cells .

<protein>B-cell-specific activator protein</protein> ( <protein>BSAP</protein> ) is a recently identified member of the <dna>Pax-gene family</dna> of <protein>transcription factors</protein> ; in the lymphoid system , <protein>BSAP</protein> is produced only in <cell_type>B cells</cell_type> .


Here , Markus Neurath , Eckhard Stuber and Warren Strober describe the molecular structure of BSAP and focus on the ability of this protein to regulate the expression of B-cell-specific genes .

Here , Markus Neurath , Eckhard Stuber and Warren Strober describe the molecular structure of <protein>BSAP</protein> and focus on the ability of this protein to regulate the expression of <dna>B-cell-specific genes</dna> .


They propose that BSAP is a key protein of B cells and that it not only influence B-cell development but also influences the balance between B-cell proliferation and immunoglobulin secretion at later stages of B-cell differentiation .

They propose that <protein>BSAP</protein> is a <protein>key protein</protein> of <cell_type>B cells</cell_type> and that it not only influence B-cell development but also influences the balance between B-cell proliferation and <protein>immunoglobulin</protein> secretion at later stages of B-cell differentiation .


Down-regulation of NF-kappa B protein levels in activated human lymphocytes by 1 , 25-dihydroxyvitamin D3 [ published erratum appears in Proc Natl Acad Sci U S A 1996 Jan 9 ; 93 ( 1 ) : 524 ]

Down-regulation of <protein>NF-kappa B protein</protein> levels in activated human lymphocytes by 1 , 25-dihydroxyvitamin D3 [ published erratum appears in Proc Natl Acad Sci U S A 1996 Jan 9 ; 93 ( 1 ) : 524 ]


The effect of 1 , 25-dihydroxyvitamin D3 [ 1 , 25 ( OH ) 2 ) D3 ] , a steroid hormone with immunomodulating properties , on nuclear factor kappa B ( NF-kappa B ) proteins was examined in in vitro activated normal human lymphocytes by Western blot analysis .

The effect of 1 , 25-dihydroxyvitamin D3 [ 1 , 25 ( OH ) 2 ) D3 ] , a steroid hormone with immunomodulating properties , on <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) proteins was examined in <cell_line>in vitro activated normal human lymphocytes</cell_line> by Western blot analysis .


Over a 72-hr period of activation , the expression of the 50-kDa NF-kappa B , p50 , and its precursor , p105 , was increased progressively .

Over a 72-hr period of activation , the expression of the <protein>50-kDa NF-kappa B</protein> , <protein>p50</protein> , and its precursor , <protein>p105</protein> , was increased progressively .


When cells were activated in the presence of 1 , 25 ( OH ) 2D3 , the levels of the mature protein as well as its precursor were decreased .


The effect of the hormone on the levels of p50 was demonstrable in the cytosolic and nuclear compartments ; it required between 4 and 8 hr and was specific , as 25-hydroxyvitamin D3 and 24 , 25-dihydroxyvitamin D3 were ineffective .

The effect of the hormone on the levels of <protein>p50</protein> was demonstrable in the cytosolic and nuclear compartments ; it required between 4 and 8 hr and was specific , as 25-hydroxyvitamin D3 and 24 , 25-dihydroxyvitamin D3 were ineffective .


Besides p50 , 1 , 25 ( OH ) 2D3 decreased the levels of another NF-kappa B protein , namely c-rel .

Besides <protein>p50</protein> , 1 , 25 ( OH ) 2D3 decreased the levels of another <protein>NF-kappa B protein</protein> , namely <protein>c-rel</protein> .


In addition , 1 , 25 ( OH ) 2D3 decreased the abundance of a specific DNA-protein complex formed upon incubation of nuclear extracts from activated lymphocytes with a labeled NF-kappa B DNA binding motif .

In addition , 1 , 25 ( OH ) 2D3 decreased the abundance of a <protein>specific DNA-protein complex</protein> formed upon incubation of nuclear extracts from activated lymphocytes with a labeled <protein>NF-kappa B DNA binding motif</protein> .


Further , 1 , 25 ( OH ) 2D3 inhibited the transcriptional activity of NF-kappa B in Jurkat cells transiently transfected with a construct containing four tandem repeats of the NF-kappa B binding sequence of the immunoglobulin kappa light chain gene linked to the chloramphenicol acetyltransferase reporter gene .

Further , 1 , 25 ( OH ) 2D3 inhibited the transcriptional activity of <protein>NF-kappa B</protein> in <cell_line>Jurkat cells</cell_line> transiently transfected with a <dna>construct</dna> containing four <dna>tandem repeats</dna> of the <dna>NF-kappa B binding sequence</dna> of the <dna>immunoglobulin kappa light chain gene</dna> linked to the <dna>chloramphenicol acetyltransferase reporter gene</dna> .


These observations demonstrate directly that there is de novo synthesis of NF-kappa B during human lymphocyte activation and suggest that this process is hormonally regulated .

These observations demonstrate directly that there is de novo synthesis of <protein>NF-kappa B</protein> during human lymphocyte activation and suggest that this process is hormonally regulated .


The myeloid zinc finger gene , MZF-1 , regulates the CD34 promoter in vitro .

The <dna>myeloid zinc finger gene</dna> , <dna>MZF-1</dna> , regulates the <dna>CD34 promoter</dna> in vitro .


MZF-1 is a C2H2 zinc finger gene encoding a putative transcriptional regulator of myeloid differentiation .

<dna>MZF-1</dna> is a <dna>C2H2 zinc finger gene</dna> encoding a <protein>putative transcriptional regulator</protein> of myeloid differentiation .


The MZF-1 protein contains 13 C2H2 zinc fingers arranged in bipartite DNA binding domains containing zinc fingers through 4 and , in the carboxy-terminus , 5 through 13 .

The <dna>MZF-1</dna> protein contains 13 <protein>C2H2 zinc fingers</protein> arranged in bipartite <protein>DNA binding domains</protein> containing <protein>zinc fingers</protein> through 4 and , in the <protein>carboxy-terminus</protein> , 5 through 13 .


We previously identified the DNA consensus binding site recognized by the two DNA binding domains .

We previously identified the <dna>DNA consensus binding site</dna> recognized by the two <protein>DNA binding domains</protein> .


To assess the transcription regulatory function of MZF-1 , the full-length MZF-1 coding region was fused to the DNA binding domain of the yeast transactivator GAL4 .

To assess the transcription regulatory function of <dna>MZF-1</dna> , the full-length <dna>MZF-1</dna> coding region was fused to the <protein>DNA binding domain</protein> of the <protein>yeast transactivator GAL4</protein> .


The expression vector was cotransfected with the chloramphenicol acetyl transferase ( CAT ) reporter gene regulated by the thymidine kinase promoter containing GAL4 DNA binding sites into NIH 3T3 , 293 , K562 , and Jurkat cell lines .

The expression vector was cotransfected with the <dna>chloramphenicol acetyl transferase ( CAT ) reporter gene</dna> regulated by the <dna>thymidine kinase promoter</dna> containing <dna>GAL4 DNA binding sites</dna> into <cell_line>NIH 3T3</cell_line> , <cell_line>293</cell_line> , <cell_line>K562</cell_line> , and <cell_line>Jurkat cell lines</cell_line> .


MZF-1 represses CAT reporter gene expression via GAL4 binding sites in the nonhematopoietic cell lines NIH 3T3 and 293 .

<dna>MZF-1</dna> represses <dna>CAT reporter gene</dna> expression via <protein>GAL4</protein> binding sites in the <cell_line>nonhematopoietic cell lines</cell_line> <cell_line>NIH 3T3</cell_line> and <cell_line>293</cell_line> .


In contrast , MZF-1 activates CAT reporter gene expression in the hematopoietic cell lines K562 and Jurkat .

In contrast , <dna>MZF-1</dna> activates <dna>CAT reporter gene</dna> expression in the <cell_line>hematopoietic cell lines</cell_line> <cell_line>K562</cell_line> and <cell_line>Jurkat</cell_line> .


The MZF-1 binding sites are present in the promoters of several genes expressed during myeloid differentiation , including the CD34 promoter .

The <dna>MZF-1 binding sites</dna> are present in the <dna>promoters</dna> of several <dna>genes</dna> expressed during myeloid differentiation , including the <dna>CD34 promoter</dna> .


MZF-1 transcriptional regulation of this physiologically relevant promoter was assessed in both hematopoietic and nonhematopoietic cell lines .

<dna>MZF-1</dna> transcriptional regulation of this <dna>physiologically relevant promoter</dna> was assessed in both <cell_line>hematopoietic</cell_line> and <cell_line>nonhematopoietic cell lines</cell_line> .


Recombinant MZF-1 protein specifically binds to the consensus binding sites in the CD34 promoter in mobility shift assays .

<protein>Recombinant MZF-1 protein</protein> specifically binds to the <dna>consensus binding sites</dna> in the <dna>CD34 promoter</dna> in mobility shift assays .


MZF-1 expression vectors were cotransfected with the luciferase reporter plasmids regulated by the CD34 promoter into both nonhematopoietic and hematopoietic cell lines .

<dna>MZF-1</dna> expression vectors were cotransfected with the <dna>luciferase reporter plasmids</dna> regulated by the <dna>CD34 promoter</dna> into both <cell_line>nonhematopoietic and hematopoietic cell lines</cell_line> .


As with the heterologous DNA binding domain , MZF-1 represses reporter gene expression in nonhematopoietic cell lines and activates expression in hematopoietic cell lines .

As with the heterologous <protein>DNA binding domain</protein> , <dna>MZF-1</dna> represses <dna>reporter gene</dna> expression in <cell_line>nonhematopoietic cell lines</cell_line> and activates expression in <cell_line>hematopoietic cell lines</cell_line> .


Activation of CD34 expression in hematopoietic cell lines is dependent on the presence of intact MZF-1 binding sites .

Activation of <protein>CD34</protein> expression in <cell_line>hematopoietic cell lines</cell_line> is dependent on the presence of intact <dna>MZF-1 binding sites</dna> .


The cell type-specific regulation of the CD34 promoter by MZF-1 suggests the presence of tissue-specific regulators/adapters or differential MZF-1 modifications that determine MZF-1 transcriptional regulatory function .

The cell type-specific regulation of the <dna>CD34 promoter</dna> by <dna>MZF-1</dna> suggests the presence of tissue-specific regulators/adapters or differential <dna>MZF-1</dna> modifications that determine <dna>MZF-1</dna> transcriptional regulatory function .


The murine BCL6 gene is induced in activated lymphocytes as an immediate early gene .

The murine <dna>BCL6 gene</dna> is induced in <cell_type>activated lymphocytes</cell_type> as an <dna>immediate early gene</dna> .


The chromosomal translocation involving 3q27 is often detected in human B-cell lymphomas , especially diffuse lymphomas with a large-cell component .

The chromosomal translocation involving <dna>3q27</dna> is often detected in <cell_type>human B-cell lymphomas</cell_type> , especially diffuse lymphomas with a large-cell component .


The BCL6 gene has been isolated from the chromosomal breakpoint in these lymphomas .

The <dna>BCL6 gene</dna> has been isolated from the chromosomal breakpoint in these lymphomas .


Here we cloned the murine BCL6 ( mBCL6 ) cDNA from the muscle cDNA library using the human BCL6 ( hBCL6 ) cDNA as a probe .

Here we cloned the <dna>murine BCL6 ( mBCL6 ) cDNA</dna> from the <dna>muscle cDNA library</dna> using the <dna>human BCL6 ( hBCL6 ) cDNA</dna> as a probe .


The predicted amino acid sequence was 95 % identical to that of hBCL6 .

The predicted amino acid sequence was 95 % identical to that of <protein>hBCL6</protein> .


It contains six repeats of the Kruppel-like zinc-finger motif that are completely identical to those of hBCL6 , indicating that the BCL6 gene is well conserved between humans and mice .

It contains six repeats of the <protein>Kruppel-like zinc-finger motif</protein> that are completely identical to those of <protein>hBCL6</protein> , indicating that the <dna>BCL6 gene</dna> is well conserved between humans and mice .


Expression of the mBCL6 gene was ubiquitously detected in adult mouse tissues including lymphatic organs .

Expression of the <dna>mBCL6 gene</dna> was ubiquitously detected in adult mouse tissues including lymphatic organs .


Furthermore , it was induced in lymphocytes activated with phorbol ester and Ca2+ ionophore within 30 min after stimulation .

Furthermore , it was induced in <cell_type>lymphocytes</cell_type> activated with phorbol ester and Ca2+ ionophore within 30 min after stimulation .


This induction was not inhibited by treatment of the cells with a protein synthesis inhibitor , cycloheximide .


These results suggest that BCL6 plays a role in activated lymphocytes as an immediate early gene .

These results suggest that <protein>BCL6</protein> plays a role in <cell_type>activated lymphocytes</cell_type> as an immediate early gene .


The role of BSAP ( Pax-5 ) in B-cell development .

The role of <protein>BSAP</protein> ( <protein>Pax-5</protein> ) in B-cell development .


The hierarchy of transcriptional control in B-cell development has recently been analyzed by targeted gene inactivation in the mouse .


In this manner , the paired box containing gene Pax-5 , encoding the B cell specific transcription factor BSAP , has been shown to play a key role in early B lymphopoiesis .

In this manner , the <dna>paired box containing gene</dna> <dna>Pax-5</dna> , encoding the <protein>B cell specific transcription factor</protein> <protein>BSAP</protein> , has been shown to play a key role in early B lymphopoiesis .


Other experimental strategies have implicated BSAP in the control of cell proliferation , isotype switching and transcription of the immunoglobulin heavy-chain gene at late stages of B-cell differentiation .

Other experimental strategies have implicated <protein>BSAP</protein> in the control of cell proliferation , isotype switching and transcription of the <protein>immunoglobulin heavy-chain</protein> gene at late stages of B-cell differentiation .


The DNA-binding properties of two heat shock factors , HSF1 and HSF3 , are induced in the avian erythroblast cell line HD6 .

The DNA-binding properties of <protein>two heat shock factors</protein> , <protein>HSF1</protein> and <protein>HSF3</protein> , are induced in the <cell_line>avian erythroblast cell line</cell_line> <cell_line>HD6</cell_line> .


Avian cells express three heat shock transcription factor ( HSF ) genes corresponding to a novel factor , HSF3 , and homologs of mouse and human HSF1 and HSF2 .

Avian cells express three <dna>heat shock transcription factor ( HSF ) genes</dna> corresponding to a <protein>novel factor</protein> , <protein>HSF3</protein> , and homologs of mouse and human <protein>HSF1</protein> and <protein>HSF2</protein> .


Analysis of the biochemical and cell biological properties of these HSFs reveals that HSF3 has properties in common with both HSF1 and HSF2 and yet has features which are distinct from both .

Analysis of the biochemical and cell biological properties of these <protein>HSFs</protein> reveals that <protein>HSF3</protein> has properties in common with both <protein>HSF1</protein> and <protein>HSF2</protein> and yet has features which are distinct from both .


HSF3 is constitutively expressed in the erythroblast cell line HD6 , the lymphoblast cell line MSB , and embryo fibroblasts , and yet its DNA-binding activity is induced only upon exposure of HD6 cells to heat shock .

<protein>HSF3</protein> is constitutively expressed in the <cell_line>erythroblast cell line HD6</cell_line> , the <cell_line>lymphoblast cell line MSB</cell_line> , and <cell_line>embryo fibroblasts</cell_line> , and yet its DNA-binding activity is induced only upon exposure of HD6 cells to heat shock .


Acquisition of HSF3 DNA-binding activity in HD6 cells is accompanied by oligomerization from a non-DNA-binding dimer to a DNA-binding trimer , whereas the effect of heat shock on HSF1 is oligomerization of an inert monomer to a DNA-binding trimer .

Acquisition of <protein>HSF3</protein> DNA-binding activity in <cell_line>HD6 cells</cell_line> is accompanied by oligomerization from a <protein>non-DNA-binding dimer</protein> to a <protein>DNA-binding trimer</protein> , whereas the effect of heat shock on <protein>HSF1</protein> is oligomerization of an <protein>inert monomer</protein> to a <protein>DNA-binding trimer</protein> .


Induction of HSF3 DNA-binding activity is delayed compared with that of HSF1 .

Induction of <protein>HSF3</protein> DNA-binding activity is delayed compared with that of <protein>HSF1</protein> .


As occurs for HSF1 , heat shock leads to the translocation of HSF3 to the nucleus .

As occurs for <protein>HSF1</protein> , heat shock leads to the translocation of <protein>HSF3</protein> to the nucleus .


HSF exhibits the properties of a transcriptional activator , as judged from the stimulatory activity of transiently overexpressed HSF3 measured by using a heat shock element-containing reporter construct and as independently assayed by the activity of a chimeric GAL4-HSF3 protein on a GAL4 reporter construct .

HSF exhibits the properties of a <protein>transcriptional activator</protein> , as judged from the stimulatory activity of <protein>transiently overexpressed HSF3</protein> measured by using a <dna>heat shock element-containing reporter construct</dna> and as independently assayed by the activity of a <protein>chimeric GAL4-HSF3 protein</protein> on a <dna>GAL4 reporter construct</dna> .


These results reveal that HSF3 is negatively regulated in avian cells and acquires DNA-binding activity in certain cells upon heat shock .

These results reveal that <protein>HSF3</protein> is negatively regulated in <cell_type>avian cells</cell_type> and acquires DNA-binding activity in certain cells upon heat shock .


Direct demonstration of NFATp dephosphorylation and nuclear localization in activated HT-2 cells using a specific NFATp polyclonal antibody .

Direct demonstration of <protein>NFATp</protein> dephosphorylation and nuclear localization in <cell_line>activated HT-2 cells</cell_line> using a specific <protein>NFATp polyclonal antibody</protein> .


Nuclear factor of activated T cells ( NFAT ) regulates transcription of a number of cytokine genes , and NFAT DNA binding activity is stimulated following T cell activation .

<protein>Nuclear factor of activated T cells</protein> ( <protein>NFAT</protein> ) regulates transcription of a number of <protein>cytokine genes</protein> , and <protein>NFAT</protein> DNA binding activity is stimulated following T cell activation .


Several lines of evidence have suggested that NFAT is a substrate for calcineurin , a serine/threonine phosphatase .

Several lines of evidence have suggested that <protein>NFAT</protein> is a substrate for <protein>calcineurin</protein> , a <protein>serine/threonine phosphatase</protein> .


Using a polyclonal antibody to murine NFATp , Western blot analysis of various mouse tissues demonstrated that the 110-130-kDa NFATp protein was highly expressed in thymus and spleen .

Using a polyclonal antibody to <protein>murine NFATp</protein> , Western blot analysis of various mouse tissues demonstrated that the 110-130-kDa <protein>NFATp protein</protein> was highly expressed in thymus and spleen .


Treatment of immunoprecipitated NFATp from untreated HT-2 cells with calcineurin resulted in the dephosphorylation of NFATp , demonstrating that NFATp is an in vitro substrate for calcineurin .

Treatment of immunoprecipitated <protein>NFATp</protein> from untreated <cell_line>HT-2 cells</cell_line> with <protein>calcineurin</protein> resulted in the dephosphorylation of <protein>NFATp</protein> , demonstrating that <protein>NFATp</protein> is an in vitro substrate for <protein>calcineurin</protein> .


NFATp immunoprecipitated from 32P-labeled HT-2 cells migrated as an approximately 120-kDa protein that was localized to the cytosol of the cells .

<protein>NFATp</protein> immunoprecipitated from <cell_line>32P-labeled HT-2 cells</cell_line> migrated as an approximately 120-kDa protein that was localized to the cytosol of the cells .


Treatment of the cells with ionomycin resulted in a decrease in the molecular weight of NFATp and a loss of 32P , consistent with NFATp dephosphorylation .

Treatment of the cells with ionomycin resulted in a decrease in the molecular weight of <protein>NFATp</protein> and a loss of 32P , consistent with <protein>NFATp</protein> dephosphorylation .


The dephosphorylation of NFATp was accompanied by localization of the protein to the nuclear fraction .

The dephosphorylation of <protein>NFATp</protein> was accompanied by localization of the protein to the nuclear fraction .


Both of these events were blocked by preincubation of the cells with FK506 , a calcineurin inhibitor , consistent with the hypothesis that NFATp is a calcineurin substrate in cells .

Both of these events were blocked by preincubation of the cells with FK506 , a <protein>calcineurin</protein> inhibitor , consistent with the hypothesis that <protein>NFATp</protein> is a <protein>calcineurin</protein> substrate in cells .


Activation and expression of the nuclear factors of activated T cells , NFATp and NFATc , in human natural killer cells : regulation upon CD16 ligand binding .

Activation and expression of the <protein>nuclear factors</protein> of <cell_type>activated T cells</cell_type> , <protein>NFATp</protein> and <protein>NFATc</protein> , in <cell_type>human natural killer cells</cell_type> : regulation upon <protein>CD16</protein> ligand binding .


The putative factors that couple the signal transduction from surface receptors to the activation of cytokine synthesis in natural killer ( NK ) cells have not been elucidated .

The putative factors that couple the signal transduction from surface receptors to the activation of <protein>cytokine</protein> synthesis in <cell_type>natural killer ( NK ) cells</cell_type> have not been elucidated .


We report here that the nuclear factor of activated T cells ( NFATp ) , a cyclosporin A ( CsA ) -sensitive factor that regulates the transcription of several cytokines , mediates CD16 -induced activation of cytokine genes in human NK cells .

We report here that the <protein>nuclear factor</protein> of <cell_type>activated T cells</cell_type> ( <protein>NFATp</protein> ) , a <protein>cyclosporin A ( CsA ) -sensitive factor</protein> that regulates the transcription of several <protein>cytokines</protein> , mediates <protein>CD16</protein> -induced activation of <protein>cytokine genes</protein> in <cell_type>human NK cells</cell_type> .


CD16 ( Fc gamma RIIIA ) -induced expression of cytokine mRNA in NK cells occurs via a CsA-sensitive and Ca ( 2+ ) -dependent mechanism .

<protein>CD16</protein> ( <protein>Fc gamma RIIIA</protein> ) -induced expression of <rna>cytokine mRNA</rna> in <cell_type>NK cells</cell_type> occurs via a CsA-sensitive and Ca ( 2+ ) -dependent mechanism .


Stimulation of NK cells with CD16 ligands induces NFAT -like DNA binding activity in the nuclear extracts from these cells , as detected in electrophoretic mobility shift assays .

Stimulation of <cell_type>NK cells</cell_type> with <protein>CD16</protein> ligands induces <protein>NFAT</protein> -like DNA binding activity in the nuclear extracts from these cells , as detected in electrophoretic mobility shift assays .


This occurs with fast kinetics after stimulation , via a CsA-sensitive and Ca ( 2+ ) -dependent mechanism that does not require de novo protein synthesis .


NK cell NFAT is present in the cytosol of nonstimulated cells , migrates to the nucleus upon stimulation , and can associate with AP-1 .

<protein>NK cell NFAT</protein> is present in the cytosol of <cell_type>nonstimulated cells</cell_type> , migrates to the nucleus upon stimulation , and can associate with <protein>AP-1</protein> .


Two distinct molecules , NFATp and NFATc , have been reported to mediate NFAT activity .

Two distinct molecules , <protein>NFATp</protein> and <protein>NFATc</protein> , have been reported to mediate <protein>NFAT</protein> activity .


The results of supershift assays using NFATp- and NFATc- specific antibodies indicate that NK cell activation early after CD16 ligand binding involves primarily , if not exclusively , NFATp , and Western blot analysis shows that this has the same electrophoretic mobility ( approximately 120 kD ) as that of T lymphocytes .

The results of supershift assays using <protein>NFATp- and NFATc- specific antibodies</protein> indicate that NK cell activation early after <protein>CD16</protein> ligand binding involves primarily , if not exclusively , <protein>NFATp</protein> , and Western blot analysis shows that this has the same electrophoretic mobility ( approximately 120 kD ) as that of <cell_type>T lymphocytes</cell_type> .


NK cells do not express NFATc constitutively , but NFATc mRNA accumulation is induced in these cells within 2 h of stimulation with CD16 ligands .

<cell_type>NK cells</cell_type> do not express <protein>NFATc</protein> constitutively , but <rna>NFATc mRNA</rna> accumulation is induced in these cells within 2 h of stimulation with CD16 ligands .


However , supershift assays using the available mAb recognizing the T cell NFATc revealed no detectable NFATc protein in nuclear and cytoplasmic extracts from CD16- or phorbol ester-stimulated cells at any time tested , up to 4 h .

However , supershift assays using the available <protein>mAb</protein> recognizing the <protein>T cell NFATc</protein> revealed no detectable <protein>NFATc</protein> protein in nuclear and cytoplasmic extracts from CD16- or <cell_line>phorbol ester-stimulated cells</cell_line> at any time tested , up to 4 h .


These results provide the first direct evidence that both CsA-sensitive transcription factors , NFATp and NFATc , are expressed in human NK cells , and that their activation and/or expression can be regulated in primary cells by a single stimulus , that , in the case of CD16 in NK cells , results in early activation of NFATp and subsequently induced expression of NFATc mRNA .

These results provide the first direct evidence that both <protein>CsA-sensitive transcription factors</protein> , <protein>NFATp</protein> and <protein>NFATc</protein> , are expressed in human <cell_type>NK cells</cell_type> , and that their activation and/or expression can be regulated in primary cells by a single stimulus , that , in the case of CD16 in <cell_type>NK cells</cell_type> , results in early activation of <protein>NFATp</protein> and subsequently induced expression of <rna>NFATc mRNA</rna> .


Interleukin 2 signaling involves the phosphorylation of Stat proteins .

Interleukin 2 signaling involves the phosphorylation of <protein>Stat proteins</protein> .


One of the most important cytokines involved in immune response regulation is interleukin 2 ( IL-2 ) , a potent activator of the proliferation and function of T lymphocytes and natural killer cells .

One of the most important <protein>cytokines</protein> involved in immune response regulation is interleukin 2 ( IL-2 ) , a potent activator of the proliferation and function of <cell_type>T lymphocytes</cell_type> and <cell_type>natural killer cells</cell_type> .


The mechanisms by which the effects of IL-2 are propagated within cells are not understood .

The mechanisms by which the effects of <protein>IL-2</protein> are propagated within cells are not understood .


While the binding of IL-2 to its receptor was recently shown to lead to the activation of two kinases , Jak-1 and Jak-3 , subsequent steps in the signaling pathway to the nucleus that lead to the activation of specific genes had not been characterized .

While the binding of <protein>IL-2</protein> to its receptor was recently shown to lead to the activation of two <protein>kinases</protein> , <protein>Jak-1</protein> and <protein>Jak-3</protein> , subsequent steps in the signaling pathway to the nucleus that lead to the activation of specific genes had not been characterized .


Since many cytokines that activate Jak kinases also lead to the tyrosine phosphorylation and activation of members of the Stat family of transcription factors , the ability of IL-2 to trigger Stat phosphorylation was examined .

Since many <protein>cytokines</protein> that activate <protein>Jak kinases</protein> also lead to the tyrosine phosphorylation and activation of members of the <protein>Stat family</protein> of <protein>transcription factors</protein> , the ability of <protein>IL-2</protein> to trigger Stat phosphorylation was examined .


Exposure of activated human T lymphocytes or of a natural killer cell line ( NKL ) to IL-2 leads to the phosphorylation of Stat1 alpha , Stat1 beta , and Stat3 , as well as of two Stat-related proteins , p94 and p95 .

Exposure of activated <cell_type>human T lymphocytes</cell_type> or of a <cell_line>natural killer cell line</cell_line> ( <cell_line>NKL</cell_line> ) to <protein>IL-2</protein> leads to the phosphorylation of <protein>Stat1 alpha</protein> , Stat1 beta , and <protein>Stat3</protein> , as well as of two <protein>Stat-related proteins</protein> , <protein>p94</protein> and <protein>p95</protein> .


p94 and p95 share homology with Stat1 at the phosphorylation site and in the Src homology 2 ( SH2 ) domain , but otherwise are immunologically distinct from Stat1 .

<protein>p94</protein> and <protein>p95</protein> share homology with <protein>Stat1</protein> at the <protein>phosphorylation site</protein> and in the <protein>Src homology 2 ( SH2 ) domain</protein> , but otherwise are immunologically distinct from <protein>Stat1</protein> .


These Stat proteins were found to translocate to the nucleus and to bind to a specific DNA sequence .

These <protein>Stat proteins</protein> were found to translocate to the nucleus and to bind to a <dna>specific DNA sequence</dna> .


These findings suggest a mechanism by which IL-2 binding to its receptor may activate specific genes involved in immune cell function .

These findings suggest a mechanism by which <protein>IL-2</protein> binding to its receptor may activate <dna>specific genes</dna> involved in immune cell function .


Expression of c-fos correlates with IFN-alpha responsiveness in Philadelphia chromosome positive chronic myelogenous leukemia .

Expression of <dna>c-fos</dna> correlates with <protein>IFN-alpha</protein> responsiveness in Philadelphia chromosome positive chronic myelogenous leukemia .


This study evaluates ( i ) constitutive levels of oncogene and p53 transcripts in chronic phase CML patients and ( ii ) their modulations subsequent to in vivo therapy with rIFN-alpha 2c .

This study evaluates ( i ) constitutive levels of <dna>oncogene</dna> and <rna>p53 transcripts</rna> in chronic phase CML patients and ( ii ) their modulations subsequent to in vivo therapy with <protein>rIFN-alpha 2c</protein> .


Peripheral blood mononuclear cells ( pbmc ) and bone marrow cells of 26 patients were examined for c-fos , c-myc , p53 and the hybrid bcr/abl mRNA levels .

<cell_type>Peripheral blood mononuclear cells</cell_type> ( <cell_type>pbmc</cell_type> ) and <cell_type>bone marrow cells</cell_type> of 26 patients were examined for c-fos , c-myc , p53 and the hybrid bcr/abl mRNA levels .


Results indicated that ( i ) constitutive c-fos transcript levels are significantly higher in patients subsequently responding to IFN-alpha therapy ( p < 0.01 ) and positively correlated with the proportion of lymphocytes ( r = 0.6895 , p < 0.01 ) and negatively with the proportion of immature cells ( r = -0.568 , p < 0.01 ) contained in the pbmc preparations tested , ( ii ) constitutive mRNA levels of the hybrid bcr/abl , c-myc and p53 are positively correlated with each other , but failed to relate to disease parameters , and ( iii ) acute and chronic in vivo exposure to IFN-alpha is accompanied by upregulation of c-fos and downregulation of c-myc mRNA levels in responder patients .

Results indicated that ( i ) constitutive <rna>c-fos transcript</rna> levels are significantly higher in patients subsequently responding to <protein>IFN-alpha</protein> therapy ( p < 0.01 ) and positively correlated with the proportion of <cell_type>lymphocytes</cell_type> ( r = 0.6895 , p < 0.01 ) and negatively with the proportion of <cell_type>immature cells</cell_type> ( r = -0.568 , p < 0.01 ) contained in the <cell_type>pbmc</cell_type> preparations tested , ( ii ) <rna>constitutive mRNA</rna> levels of the <dna>hybrid bcr/abl</dna> , <dna>c-myc</dna> and <dna>p53</dna> are positively correlated with each other , but failed to relate to disease parameters , and ( iii ) acute and chronic in vivo exposure to <protein>IFN-alpha</protein> is accompanied by upregulation of <dna>c-fos</dna> and downregulation of <rna>c-myc mRNA</rna> levels in responder patients .


Menopause is associated with a significant increase in blood monocyte number and a relative decrease in the expression of estrogen receptors in human peripheral monocytes .

Menopause is associated with a significant increase in blood monocyte number and a relative decrease in the expression of <protein>estrogen receptors</protein> in <cell_type>human peripheral monocytes</cell_type> .


PROBLEM : The clinical significance of the differential expression of estrogen receptor ( ER ) in human monocytes was evaluated .

PROBLEM : The clinical significance of the differential expression of <protein>estrogen receptor</protein> ( <protein>ER</protein> ) in <cell_type>human monocytes</cell_type> was evaluated .


METHOD : Two color flow cytometry analysis was used on peripheral blood samples of young and postmenopausal females and postmenopausal females treated with estrogen replacement therapy .


In addition , the monocyte and lymphocyte counts and the blood estrogen levels of each patient were determine .


RESULTS : During menopause there is a significant decrease in the percentage of ER positive monocytes , and an increase in blood monocyte number , which declines following estrogen replacement therapy to values of the young .

RESULTS : During menopause there is a significant decrease in the percentage of <cell_type>ER positive monocytes</cell_type> , and an increase in <cell_type>blood monocyte</cell_type> number , which declines following estrogen replacement therapy to values of the young .


CONCLUSIONS : These findings suggest that estrogen modulates the monocyte numbers and its effects may be mediated through the ER in the monocytes .

CONCLUSIONS : These findings suggest that estrogen modulates the <cell_type>monocyte</cell_type> numbers and its effects may be mediated through the <protein>ER</protein> in the <cell_type>monocytes</cell_type> .


Staphylococcal enterotoxins modulate interleukin 2 receptor expression and ligand-induced tyrosine phosphorylation of the Janus protein-tyrosine kinase 3 ( Jak3 ) and signal transducers and activators of transcription ( Stat proteins ) .

<protein>Staphylococcal enterotoxins</protein> modulate <protein>interleukin 2 receptor</protein> expression and ligand-induced tyrosine phosphorylation of the <protein>Janus protein-tyrosine kinase 3</protein> ( <protein>Jak3</protein> ) and <protein>signal transducers and activators of transcription</protein> ( <protein>Stat proteins</protein> ) .


Staphylococcal enterotoxins ( SE ) stimulate T cells expressing the appropriate variable region beta chain of ( V beta ) T-cell receptors and have been implicated in the pathogenesis of several autoimmune diseases .

<protein>Staphylococcal enterotoxins</protein> ( <protein>SE</protein> ) stimulate <cell_type>T cells</cell_type> expressing the appropriate <protein>variable region beta chain of ( V beta ) T-cell receptors</protein> and have been implicated in the pathogenesis of several autoimmune diseases .


Depending on costimulatory signals , SE induce either proliferation or anergy in T cells .

Depending on costimulatory signals , <protein>SE</protein> induce either proliferation or anergy in <cell_type>T cells</cell_type> .


In addition , SE can induce an interleukin-2 ( IL-2 ) nonresponsive state and apoptosis .

In addition , <protein>SE</protein> can induce an <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) nonresponsive state and apoptosis .


Here , we show that SE induce dynamic changes in the expression of and signal transduction through the IL-2 receptor ( IL-2R ) beta and gamma chains ( IL-2R beta and IL-2R gamma ) in human antigen-specific CD4+ T-cell lines .

Here , we show that <protein>SE</protein> induce dynamic changes in the expression of and signal transduction through the <protein>IL-2 receptor ( IL-2R ) beta and gamma chains</protein> ( <protein>IL-2R beta</protein> and <protein>IL-2R gamma</protein> ) in <cell_line>human antigen-specific CD4+ T-cell lines</cell_line> .


Thus , after 4 hr of exposure to SEA and SEB , the expression of IL-2R beta was down-regulated , IL-2R gamma was slightly up-regulated , while IL-2R alpha remained largely unaffected .

Thus , after 4 hr of exposure to <protein>SEA</protein> and <protein>SEB</protein> , the expression of <protein>IL-2R beta</protein> was down-regulated , <protein>IL-2R gamma</protein> was slightly up-regulated , while <protein>IL-2R alpha</protein> remained largely unaffected .


The changes in the composition of IL-2Rs were accompanied by inhibition of IL-2 -induced tyrosine phosphorylation of the Janus protein-tyrosine kinase 3 ( Jak3 ) and signal transducers and activators of transcription called Stat3 and Stat5 .

The changes in the composition of <protein>IL-2Rs</protein> were accompanied by inhibition of <protein>IL-2</protein> -induced tyrosine phosphorylation of the <protein>Janus protein-tyrosine kinase 3</protein> ( <protein>Jak3</protein> ) and <protein>signal transducers and activators of transcription</protein> called <protein>Stat3</protein> and <protein>Stat5</protein> .


In parallel experiments , IL-2 -driven proliferation was inhibited significantly .

In parallel experiments , <protein>IL-2</protein> -driven proliferation was inhibited significantly .


After 16 hr of exposure to SE , the expression of IL-2R beta remained low , while that of IL2R alpha and IL2R gamma was further up-regulated , and ligand-induced tyrosine phosphorylation of Jak3 and Stat proteins was partly normalized .

After 16 hr of exposure to <protein>SE</protein> , the expression of <protein>IL-2R beta</protein> remained low , while that of <protein>IL2R alpha</protein> and <protein>IL2R gamma</protein> was further up-regulated , and ligand-induced tyrosine phosphorylation of <protein>Jak3</protein> and <protein>Stat proteins</protein> was partly normalized .


Yet , IL-2 -driven proliferation remained profoundly inhibited , suggesting that signaling events other than Jak3 /Stat activation had also been changed following SE stimulation .

Yet , <protein>IL-2</protein> -driven proliferation remained profoundly inhibited , suggesting that signaling events other than <protein>Jak3</protein> <protein>/Stat</protein> activation had also been changed following <protein>SE</protein> stimulation .


In conclusion , our data suggest that SE can modulate IL-2R expression and signal transduction involving the Jak/Stat pathway in CD4+ T-cell lines .

In conclusion , our data suggest that <protein>SE</protein> can modulate <protein>IL-2R</protein> expression and signal transduction involving the <protein>Jak/Stat</protein> pathway in <cell_line>CD4+ T-cell lines</cell_line> .


Constitutive NF-kappa B activation , enhanced granulopoiesis , and neonatal lethality in I kappa B alpha -deficient mice .

Constitutive <protein>NF-kappa B</protein> activation , enhanced granulopoiesis , and neonatal lethality in <protein>I kappa B alpha</protein> -deficient mice .


Transcription factors belonging to the NF-kappa B family are controlled by inhibitory I kappa B proteins , mainly I kappa B alpha and I kappa B beta .

<protein>Transcription factors</protein> belonging to the <protein>NF-kappa B family</protein> are controlled by <protein>inhibitory I kappa B proteins</protein> , mainly <protein>I kappa B alpha</protein> and <protein>I kappa B beta</protein> .


Apparently normal at birth , I kappa B alpha -/- mice exhibit severe runting , skin defects , and extensive granulopoiesis postnatally , typically dying by 8 days .

Apparently normal at birth , <protein>I kappa B alpha</protein> -/- mice exhibit severe runting , skin defects , and extensive granulopoiesis postnatally , typically dying by 8 days .


Hematopoietic tissues from these mice display elevated levels of both nuclear NF-kappa B and mRNAs of some , but not all , genes thought to be regulated by NF-kappa B .

Hematopoietic tissues from these mice display elevated levels of both <protein>nuclear NF-kappa B</protein> and <rna>mRNAs</rna> of some , but not all , genes thought to be regulated by <protein>NF-kappa B</protein> .


NF-kappa B elevation results in these phenotypic abnormalities because mice lacking both I kappa B alpha and the p50 subunit of NF-kappa B show a dramatically delayed onset of abnormalities .

<protein>NF-kappa B</protein> elevation results in these phenotypic abnormalities because mice lacking both <protein>I kappa B alpha</protein> and the <protein>p50 subunit</protein> of <protein>NF-kappa B</protein> show a dramatically delayed onset of abnormalities .


In contrast to hematopoietic cells , I kappa B alpha-/- embryonic fibroblasts show minimal constitutive NF-kappa B , as well as normal signal-dependent NF-kappa B activation that is concomitant with I kappa B beta degradation .

In contrast to <cell_type>hematopoietic cells</cell_type> , <cell_line>I kappa B alpha-/- embryonic fibroblasts</cell_line> show minimal <protein>constitutive NF-kappa B</protein> , as well as normal signal-dependent <protein>NF-kappa B</protein> activation that is concomitant with <protein>I kappa B beta</protein> degradation .


Our results indicate that I kappa b beta , but not I kappa B alpha , is required for the signal-dependent activation of NF-kappa B in fibroblasts .

Our results indicate that I kappa b beta , but not <protein>I kappa B alpha</protein> , is required for the signal-dependent activation of <protein>NF-kappa B</protein> in <cell_type>fibroblasts</cell_type> .


However , I kappa B alpha is required for the postinduction repression of NF-kappa B in fibroblasts .

However , <protein>I kappa B alpha</protein> is required for the postinduction repression of <protein>NF-kappa B</protein> in <cell_type>fibroblasts</cell_type> .


These results define distinct roles for the two forms of I kappa B and demonstrate the necessity for stringent control of NF-kappa B .

These results define distinct roles for the two forms of <protein>I kappa B</protein> and demonstrate the necessity for stringent control of <protein>NF-kappa B</protein> .


Interleukin-7 can induce the activation of Jak 1 , Jak 3 and STAT 5 proteins in murine T cells .

<protein>Interleukin-7</protein> can induce the activation of <protein>Jak 1</protein> , <protein>Jak 3</protein> and <protein>STAT 5 proteins</protein> in murine <cell_type>T cells</cell_type> .


The activation of Janus protein tyrosine kinases ( Jak ) and STAT ( signal transducer and activator of transcription ) proteins has recently been linked to the signal transduction mechanism of several cytokines .

The activation of <protein>Janus protein tyrosine kinases</protein> ( <protein>Jak</protein> ) and <protein>STAT ( signal transducer and activator of transcription ) proteins</protein> has recently been linked to the signal transduction mechanism of several <protein>cytokines</protein> .


IL-7 was observed to induce a rapid and dose-dependent tyrosine phosphorylation of Jak 1 and Jak 3 and concomitantly , the tyrosine phosphorylation and DNA binding activity of multiple STAT proteins .

<protein>IL-7</protein> was observed to induce a rapid and dose-dependent tyrosine phosphorylation of <protein>Jak 1</protein> and <protein>Jak 3</protein> and concomitantly , the tyrosine phosphorylation and DNA binding activity of multiple <protein>STAT proteins</protein> .


The STAT proteins utilized by IL-7 were identical to those induced by IL-2 and could be identified as various STAT 5 isoforms .

The <protein>STAT proteins</protein> utilized by <protein>IL-7</protein> were identical to those induced by <protein>IL-2</protein> and could be identified as various <protein>STAT 5 isoforms</protein> .


Moreover , the induction of both Jak 1 and 3 , and STAT 5 activity strongly correlated with the growth-promoting effects of IL-7 , suggesting that this signal transduction mechanism may play a key role in IL-7 -induced proliferation .

Moreover , the induction of both <protein>Jak 1 and 3</protein> , and <protein>STAT 5</protein> activity strongly correlated with the growth-promoting effects of <protein>IL-7</protein> , suggesting that this signal transduction mechanism may play a key role in <protein>IL-7</protein> -induced proliferation .


Cytokine -modulating activity of tepoxalin , a new potential antirheumatic .

<protein>Cytokine</protein> -modulating activity of tepoxalin , a new potential antirheumatic .


Tepoxalin is a new dual cyclooxygenase/5-lipoxygenase anti-inflammatory compound currently under clinical investigation .


It has been shown to possess anti-inflammatory activity in a variety of animal models and more recently to inhibit IL-2 induced signal transduction .

It has been shown to possess anti-inflammatory activity in a variety of animal models and more recently to inhibit <protein>IL-2</protein> induced signal transduction .


The current study was conducted to evaluate the cytokine modulating activity of tepoxalin and the role of iron in these effects .

The current study was conducted to evaluate the <protein>cytokine</protein> modulating activity of tepoxalin and the role of iron in these effects .


In human peripheral blood mononuclear cells ( PBMC ) stimulated with OKT3/PMA , tepoxalin inhibited lymphocyte proliferation with an IC50 of 6 microM .

In <cell_type>human peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) stimulated with OKT3/PMA , tepoxalin inhibited <cell_type>lymphocyte</cell_type> proliferation with an IC50 of 6 microM .


Additionally , it inhibited the production of LTB4 ( IC50 = 0.5 microM ) and the cytokines IL-2 , IL-6 and TNF alpha ( IC50 = 10-12 microM ) .

Additionally , it inhibited the production of <protein>LTB4</protein> ( IC50 = 0.5 microM ) and the <protein>cytokines</protein> <protein>IL-2</protein> , <protein>IL-6</protein> and <protein>TNF alpha</protein> ( IC50 = 10-12 microM ) .


Cytotoxicity was not demonstrated at these concentrations .


Add-back experiments with either cytokines ( IL-2 or IL-6 ) , LTB4 or conditioned media failed to restore the proliferative response in the presence of tepoxalin .

Add-back experiments with either <protein>cytokines</protein> ( <protein>IL-2</protein> or <protein>IL-6</protein> ) , <protein>LTB4</protein> or conditioned media failed to restore the proliferative response in the presence of tepoxalin .


However , the concurrent addition of iron ( in the form of ferrous or ferric chloride and other iron salts ) reversed the inhibition of proliferation caused by tepoxalin .


Tepoxalin also inhibits the activation of NF kappa B , a transcription factor which acts on several cytokine genes .

Tepoxalin also inhibits the activation of <protein>NF kappa B</protein> , a <protein>transcription factor</protein> which acts on several <dna>cytokine genes</dna> .


Tepoxalin 's effect on NF kappa B is also reversed by the addition of iron salts .

Tepoxalin 's effect on <protein>NF kappa B</protein> is also reversed by the addition of iron salts .


These data suggest that the action of tepoxalin to inhibit proliferation in PBMC may be at least in part due to its ability to reduce the amount of available iron resulting in decreased activation of NF kappa B and subsequent inhibition of cytokine production .

These data suggest that the action of tepoxalin to inhibit proliferation in <cell_type>PBMC</cell_type> may be at least in part due to its ability to reduce the amount of available iron resulting in decreased activation of <protein>NF kappa B</protein> and subsequent inhibition of <protein>cytokine</protein> production .


N- and C-terminal sequences control degradation of MAD3/I kappa B alpha in response to inducers of NF-kappa B activity .

<protein>N- and C-terminal sequences</protein> control degradation of <protein>MAD3/I kappa B alpha</protein> in response to inducers of <protein>NF-kappa B</protein> activity .


The proteolytic degradation of the inhibitory protein MAD3/I kappa B alpha in response to extracellular stimulation is a prerequisite step in the activation of the transcription factor NF-kappa B .

The proteolytic degradation of the <protein>inhibitory protein</protein> <protein>MAD3/I kappa B alpha</protein> in response to extracellular stimulation is a prerequisite step in the activation of the <protein>transcription factor</protein> <protein>NF-kappa B</protein> .


Analysis of the expression of human I kappa B alpha protein in stable transfectants of mouse 70Z/3 cells shows that , as for the endogenous murine protein , exogenous I kappa B alpha is degraded in response to inducers of NF-kappa B activity , such as phorbol myristate acetate or lipopolysaccharide .

Analysis of the expression of <protein>human I kappa B alpha protein</protein> in stable transfectants of <cell_line>mouse 70Z/3 cells</cell_line> shows that , as for the endogenous murine protein , exogenous <protein>I kappa B alpha</protein> is degraded in response to inducers of <protein>NF-kappa B</protein> activity , such as phorbol myristate acetate or lipopolysaccharide .


In addition , pretreatment of the cells with the proteasome inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and , in agreement with previous studies , stabilizes a hyperphosphorylated form of the human I kappa B alpha protein .

In addition , pretreatment of the cells with the <protein>proteasome</protein> inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and , in agreement with previous studies , stabilizes a hyperphosphorylated form of the <protein>human I kappa B alpha protein</protein> .


By expressing mutant forms of the human protein in this cell line , we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of I kappa B alpha .

By expressing mutant forms of the human protein in this <cell_line>cell line</cell_line> , we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of <protein>I kappa B alpha</protein> .


Our results show that deletion of the C terminus of the I kappa B alpha molecule up to amino acid 279 abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation .

Our results show that deletion of the <protein>C terminus</protein> of the <protein>I kappa B alpha</protein> molecule up to <protein>amino acid 279</protein> abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation .


Further analysis reveals that the inducible phosphorylation of I kappa B alpha maps to two serines in the N terminus of the protein ( residues 32 and 36 ) and that the mutation of either residue is sufficient to abolish ligand-induced degradation , whereas both residues must be mutated to abolish inducible phosphorylation of the protein .

Further analysis reveals that the inducible phosphorylation of <protein>I kappa B alpha</protein> maps to two serines in the <protein>N terminus</protein> of the protein ( residues 32 and 36 ) and that the mutation of either residue is sufficient to abolish ligand-induced degradation , whereas both residues must be mutated to abolish inducible phosphorylation of the protein .


( ABSTRACT TRUNCATED AT 250 WORDS )


Microtubules mediate cellular 25-hydroxyvitamin D3 trafficking and the genomic response to 1 , 25-dihydroxyvitamin D3 in normal human monocytes .

<protein>Microtubules</protein> mediate cellular 25-hydroxyvitamin D3 trafficking and the genomic response to 1 , 25-dihydroxyvitamin D3 in normal <cell_type>human monocytes</cell_type> .


The genomic actions of 1 , 25-dihydroxyvitamin D3 ( 1 , 25 ( OH ) 2D3 ) are mediated by the intracellular vitamin D receptor ( VDR ) .

The genomic actions of 1 , 25-dihydroxyvitamin D3 ( 1 , 25 ( OH ) 2D3 ) are mediated by the intracellular <protein>vitamin D receptor</protein> ( <protein>VDR</protein> ) .


Although immunocytochemistry has shown that disruption of microtubular assembly prevents nuclear access of the sterol-VDR complex , the role of microtubules in the response to 1 , 25 ( OH ) 2D3 has not been studied in viable cells .

Although immunocytochemistry has shown that disruption of microtubular assembly prevents nuclear access of the <protein>sterol-VDR complex</protein> , the role of <protein>microtubules</protein> in the response to 1 , 25 ( OH ) 2D3 has not been studied in <cell_type>viable cells</cell_type> .


Our studies examined this interaction in normal human monocytes .

Our studies examined this interaction in normal <cell_type>human monocytes</cell_type> .


Monocytes convert 25 ( OH ) D3 to 1 , 25 ( OH ) 2D3 and to 24-hydroxylated metabolites more polar than 1 , 25 ( OH ) 2D3 .


Microtubule disruption totally abolished the ability of exogenous 1 , 25 ( OH ) 2D3 to suppress its own synthesis and to induce 24-hydroxylase mRNA and activity , without affecting either total 1 , 25 ( OH ) 2D3 uptake or maximal 1 , 25 ( OH ) 2D3 -VDR binding .

Microtubule disruption totally abolished the ability of exogenous 1 , 25 ( OH ) 2D3 to suppress its own synthesis and to induce <rna>24-hydroxylase mRNA</rna> and activity , without affecting either total 1 , 25 ( OH ) 2D3 uptake or maximal 1 , 25 ( OH ) 2D3 <protein>-VDR</protein> binding .


Thus , intact microtubules are essential for 1 , 25 ( OH ) 2D3-dependent modulation of gene transcription .

Thus , intact <protein>microtubules</protein> are essential for 1 , 25 ( OH ) 2D3-dependent modulation of gene transcription .


Interestingly , microtubule disruption also decreased monocyte 1 , 25 ( OH ) 2D3 synthesis , not by decreasing the Vmax of monocyte mitochondrial 1 alpha-hydroxylase but through an increase in the Km for 25 ( OH ) 2D3 .

Interestingly , <protein>microtubule</protein> disruption also decreased <cell_type>monocyte</cell_type> 1 , 25 ( OH ) 2D3 synthesis , not by decreasing the Vmax of <protein>monocyte mitochondrial 1 alpha-hydroxylase</protein> but through an increase in the Km for 25 ( OH ) 2D3 .


We examined 25 ( OH ) D3 transport .


Microtubule disruption did not affect total cellular 25 ( OH ) D3 uptake but reduced its intracellular trafficking to the mitochondria .


Thus , microtubules participate in intracellular 25 ( OH ) D3 transport , and their integrity determines normal 1 , 25 ( OH ) 2D3 synthesis .

Thus , <protein>microtubules</protein> participate in intracellular 25 ( OH ) D3 transport , and their integrity determines normal 1 , 25 ( OH ) 2D3 synthesis .


Relationship between Rap1 protein phosphorylation and regulation of Ca2+ transport in platelets : a new approach .

Relationship between <protein>Rap1 protein</protein> phosphorylation and regulation of Ca2+ transport in <cell_type>platelets</cell_type> : a new approach .


Although the interrelationship between the two messengers Ca2+ and cyclic AMP in platelet function is well documented , its mechanism of action still remains to be established .


We investigated here the question of the regulation of platelet Ca ( 2+ ) -ATPases by cyclic AMP through the phosphorylation of the Rap1 protein using a pathological model .

We investigated here the question of the regulation of <protein>platelet Ca ( 2+ ) -ATPases</protein> by cyclic AMP through the phosphorylation of the <protein>Rap1 protein</protein> using a pathological model .


We first found experimental conditions where Ca ( 2+ ) -transport by platelet membrane vesicles appeared to be dependent on the phosphorylation of the Rap1 protein .

We first found experimental conditions where Ca ( 2+ ) -transport by platelet membrane vesicles appeared to be dependent on the phosphorylation of the <protein>Rap1 protein</protein> .


Then , we studied platelets of patients with congestive heart failure for their expression of the potential 97 kDa Ca ( 2+ ) -ATPase target of regulation through the Rap1 protein as well as the phosphorylation of the Rap1 protein using the catalytic subunit of the cyclic AMP-dependent protein kinase ( C. Sub . ) .

Then , we studied <cell_type>platelets</cell_type> of patients with congestive heart failure for their expression of the potential <protein>97 kDa Ca ( 2+ ) -ATPase target</protein> of regulation through the <protein>Rap1 protein</protein> as well as the phosphorylation of the <protein>Rap1 protein</protein> using the <protein>catalytic subunit</protein> of the <protein>cyclic AMP-dependent protein kinase</protein> ( <protein>C. Sub .</protein> ) .


In the first patients studied , we found no significant modification in the expression of the 97 kDa Ca ( 2+ ) -ATPase by Western blotting using the PL/IM 430 monoclonal antibody which specifically recognized this isoform .

In the first patients studied , we found no significant modification in the expression of the <protein>97 kDa Ca ( 2+ ) -ATPase</protein> by Western blotting using the <protein>PL/IM 430 monoclonal antibody</protein> which specifically recognized this isoform .


In contrast , the Rap1 protein was differentially phosphorylated when using 15 micrograms/ml of the C. Sub .

In contrast , the <protein>Rap1 protein</protein> was differentially phosphorylated when using 15 micrograms/ml of the <protein>C. Sub .</protein>


These results allowed us to use these pathological platelets to study the relationship between the expression of Rap1 protein and the regulation of Ca2+ transport by selecting a patient with severe heart failure .

These results allowed us to use these pathological <cell_type>platelets</cell_type> to study the relationship between the expression of <protein>Rap1 protein</protein> and the regulation of Ca2+ transport by selecting a patient with severe heart failure .


We could show a decrease in the expression as well as in the phosphorylation of Rap1 protein and demonstrate a lower effect of C. Sub . on Ca2+ transport .

We could show a decrease in the expression as well as in the phosphorylation of <protein>Rap1 protein</protein> and demonstrate a lower effect of <protein>C. Sub .</protein> on Ca2+ transport .


Finally , by studying a further series of patients , we could confirm that the decrease in Rap1 protein expression in heart failure , whatever its extent , was variable , and could strictly correlate the expression of Rap1 protein with the stimulatory effect of C. Sub . on Ca2+ transport .

Finally , by studying a further series of patients , we could confirm that the decrease in <protein>Rap1 protein</protein> expression in heart failure , whatever its extent , was variable , and could strictly correlate the expression of <protein>Rap1 protein</protein> with the stimulatory effect of <protein>C. Sub .</protein> on Ca2+ transport .


Besides the evidence for regulation of the expression of the Rap1 protein in platelets from patients with heart failure , these findings constitute a new approach in favour of the regulation of platelet Ca2+ transport through the phosphorylation of the Rap1 protein .

Besides the evidence for regulation of the expression of the <protein>Rap1 protein</protein> in <cell_type>platelets</cell_type> from patients with heart failure , these findings constitute a new approach in favour of the regulation of platelet Ca2+ transport through the phosphorylation of the <protein>Rap1 protein</protein> .


An IRF-1 -dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes .

An <protein>IRF-1</protein> -dependent pathway of DNA damage-induced apoptosis in <cell_line>mitogen-activated T lymphocytes</cell_line> .


Lymphocytes are particularly susceptible to DNA damage-induced apoptosis , a response which may serve as a form of 'altruistic suicide ' to counter their intrinsic high potential for mutation and clonal expansion .

<cell_line>Lymphocytes</cell_line> are particularly susceptible to DNA damage-induced apoptosis , a response which may serve as a form of 'altruistic suicide ' to counter their intrinsic high potential for mutation and clonal expansion .


The tumour suppressor p53 has been shown to regulate this type of apoptosis in thymocytes , but an as yet unknown , p53 -independent pathway ( s ) appears to mediate the same event in mitogen-activated mature T lymphocytes .

The <protein>tumour suppressor p53</protein> has been shown to regulate this type of apoptosis in <cell_type>thymocytes</cell_type> , but an as yet unknown , <protein>p53</protein> -independent pathway ( s ) appears to mediate the same event in <cell_line>mitogen-activated mature T lymphocytes</cell_line> .


Here we show DNA damage-induced apoptosis in these T lymphocytes is dependent on the antioncogenic transcription factor interferon regulatory factor ( IRF ) -1 .

Here we show DNA damage-induced apoptosis in these <cell_type>T lymphocytes</cell_type> is dependent on the <protein>antioncogenic transcription factor interferon regulatory factor</protein> <protein>( IRF ) -1</protein> .


Thus two different anti-onco-genic transcription factors , p53 and IRF-1 , are required for distinct apoptotic pathways in T lymphocytes .

Thus two different <protein>anti-onco-genic transcription factors</protein> , <protein>p53</protein> and <protein>IRF-1</protein> , are required for distinct apoptotic pathways in <cell_type>T lymphocytes</cell_type> .


We also show that mitogen induction of the interleukin-1 beta converting enzyme ( ICE ) gene , a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3 , is IRF-1 -dependent .

We also show that mitogen induction of the <dna>interleukin-1 beta converting enzyme ( ICE ) gene</dna> , a <protein>mammalian homologue</protein> of the <dna>Caenorhabditis elegans cell death gene</dna> <dna>ced-3</dna> , is <protein>IRF-1</protein> -dependent .


Ectopic overexpression of IRF-1 results in the activation of the endogenous gene for ICE and enhances the sensitivity of cells to radiation-induced apoptosis .

Ectopic overexpression of <protein>IRF-1</protein> results in the activation of the <dna>endogenous gene</dna> for <protein>ICE</protein> and enhances the sensitivity of cells to radiation-induced apoptosis .


Circadian rhythm of glucocorticoid receptors in human peripheral leukocytes and their reactivity to glucocorticoids .

Circadian rhythm of <protein>glucocorticoid receptors</protein> in <cell_type>human peripheral leukocytes</cell_type> and their reactivity to glucocorticoids .


1 ) There exists a CR of GR in human leukocytes , PMN , and monocytes with the peak values from 0400 to 0800 hr and the trough values between 2300 and 0000 hr .

1 ) There exists a CR of <protein>GR</protein> in <cell_type>human leukocytes</cell_type> , <cell_type>PMN</cell_type> , and <cell_type>monocytes</cell_type> with the peak values from 0400 to 0800 hr and the trough values between 2300 and 0000 hr .


The difference between them was significant statistically .


2 ) The FI of the chemotactic migration rate of PMN by cortisol also showed diurnal changes which were synchronous with that of GR .

2 ) The FI of the chemotactic migration rate of <cell_type>PMN</cell_type> by cortisol also showed diurnal changes which were synchronous with that of <protein>GR</protein> .


This indicates that the CR of GR may be of functional significance .

This indicates that the CR of <protein>GR</protein> may be of functional significance .


3 ) In Cushing 's syndrome , the CR of GR was normal in spite of the fact that the CR of plasma cortisol was disturbed .

3 ) In Cushing 's syndrome , the CR of <protein>GR</protein> was normal in spite of the fact that the CR of plasma cortisol was disturbed .


This indicates the independency of the CR of GR from that of cortisol .

This indicates the independency of the CR of <protein>GR</protein> from that of cortisol .


4 ) In apoplexy caused by brain ischemia , the CR of GR was abolished in patients with basal lesions but preserved when the lesions were located in the cerebral cortex .

4 ) In apoplexy caused by brain ischemia , the CR of <protein>GR</protein> was abolished in patients with basal lesions but preserved when the lesions were located in the cerebral cortex .


These results strongly suggest that the main `` circadian pacemaker '' of GR is located in the basal brain , most probably in the suprachiasmatic nuclei as has been suggested for rodents .

These results strongly suggest that the main `` circadian pacemaker '' of <protein>GR</protein> is located in the basal brain , most probably in the suprachiasmatic nuclei as has been suggested for rodents .


B-lymphoblastoid cell lines from multiple sclerosis patients and a healthy control producing a putative new human retrovirus and Epstein-Barr virus .

<cell_line>B-lymphoblastoid cell lines</cell_line> from multiple sclerosis patients and a healthy control producing a putative new human retrovirus and Epstein-Barr virus .


On several occasions we have observed retrovirus-like particles ( RVLPs ) by transmission electron microscopy ( EM ) of cultured T cells from a patient with MS .

On several occasions we have observed retrovirus-like particles ( RVLPs ) by transmission electron microscopy ( EM ) of <cell_line>cultured T cells</cell_line> from a patient with MS .


Later we established spontaneously formed B-lymphoblastoid cell lines ( LCLs ) from a patient with an MS-like disease and from another patient with MS who had a reactivated Epstein-Barr virus ( EBV ) infection .

Later we established spontaneously formed <cell_line>B-lymphoblastoid cell lines</cell_line> ( <cell_line>LCLs</cell_line> ) from a patient with an MS-like disease and from another patient with MS who had a reactivated Epstein-Barr virus ( EBV ) infection .


Both LCLs were found by EM to produce RVLP and EBV particles .

Both <cell_line>LCLs</cell_line> were found by EM to produce RVLP and EBV particles .


Reverse transcriptase ( RT ) assays were positive in purified viral material from both LCLs .

Reverse transcriptase ( RT ) assays were positive in purified viral material from both <cell_line>LCLs</cell_line> .


To substantiate these findings we initiated an intensified culturing procedure and were able to establish LCLs from 5 out of 21 consecutive MS patients and 1 out of 13 consecutive healthy controls .

To substantiate these findings we initiated an intensified culturing procedure and were able to establish <cell_line>LCLs</cell_line> from 5 out of 21 consecutive MS patients and 1 out of 13 consecutive healthy controls .


All LCLs were found to produce both RVLP and EBV particles by EM .

All <cell_line>LCLs</cell_line> were found to produce both RVLP and EBV particles by EM .


Whether the putative new retrovirus ( es ) and EBV have any causal relationship to MS is still not known , but the findings support this possibility .


Identification of an ionomycin/cyclosporin A-responsive element within the human T cell receptor gamma enhancer .

Identification of an <dna>ionomycin/cyclosporin A-responsive element</dna> within the <dna>human T cell receptor gamma enhancer</dna> .


Activation through the Ca2+/ calcineurin pathway is essential to the transcription of many cytokine genes .

Activation through the Ca2+/ <protein>calcineurin</protein> pathway is essential to the transcription of many <dna>cytokine genes</dna> .


The conserved cis-acting sequence , GGAAAA , and transcription factors binding to this sequence are involved in the response to increased intracellular Ca2+ concentrations .

The <dna>conserved cis-acting sequence</dna> , GGAAAA , and <protein>transcription factors</protein> binding to this sequence are involved in the response to increased intracellular Ca2+ concentrations .


Here we report the identification and importance of the same sequence in a non-cytokine gene , the human T cell receptor gamma ( TCRG ) enhancer .

Here we report the identification and importance of the same sequence in a <dna>non-cytokine gene</dna> , the <dna>human T cell receptor gamma ( TCRG ) enhancer</dna> .


Results from site-directed mutations and electrophoretic mobility shift assays strongly suggest that this sequence mediates the ionomycin-induced activation of the TCRG enhancer .

Results from site-directed mutations and electrophoretic mobility shift assays strongly suggest that this sequence mediates the ionomycin-induced activation of the <dna>TCRG enhancer</dna> .


Our studies provide an explanation for a previous observation that TCRG mRNA levels , but not mRNA levels for T cell receptor alpha and -beta , are increased by ionomycin treatment .

Our studies provide an explanation for a previous observation that <rna>TCRG mRNA</rna> levels , but not mRNA levels for <protein>T cell receptor alpha and -beta</protein> , are increased by ionomycin treatment .


Coexpression of NF-kappa B/Rel and Sp1 transcription factors in human immunodeficiency virus 1-induced , dendritic cell-T-cell syncytia .

Coexpression of <protein>NF-kappa B/Rel</protein> and <protein>Sp1</protein> <protein>transcription factors</protein> in human immunodeficiency virus 1-induced , dendritic cell-T-cell syncytia .


Productive infection of T cells with human immunodeficiency virus 1 ( HIV-1 ) typically requires that the T cells be stimulated with antigens or mitogens .

Productive infection of <cell_type>T cells</cell_type> with human immunodeficiency virus 1 ( HIV-1 ) typically requires that the <cell_type>T cells</cell_type> be stimulated with antigens or mitogens .


This requirement has been attributed to the activation of the transcription factor NF-kappa B , which synergizes with the constitutive transcription factor Sp1 to drive the HIV-1 promoter .

This requirement has been attributed to the activation of the <protein>transcription factor</protein> <protein>NF-kappa B</protein> , which synergizes with the <protein>constitutive transcription factor</protein> <protein>Sp1</protein> to drive the <dna>HIV-1 promoter</dna> .


Recently , we have found that vigorous replication of HIV-1 takes place in nonactivated memory T cells after syncytium formation with dendritic cells ( DCs ) .

Recently , we have found that vigorous replication of HIV-1 takes place in nonactivated <cell_type>memory T cells</cell_type> after syncytium formation with <cell_type>dendritic cells</cell_type> ( <cell_type>DCs</cell_type> ) .


These syncytia lack activated cells as determined by an absence of staining for Ki-67 cell cycle antigen .

These syncytia lack <cell_type>activated cells</cell_type> as determined by an absence of staining for Ki-67 cell cycle antigen .


The expression and activity of NF-kappa B and Sp1 were , therefore , analyzed in isolated T cells and DCs from humans and mice .

The expression and activity of <protein>NF-kappa B</protein> and <protein>Sp1</protein> were , therefore , analyzed in isolated <cell_type>T cells</cell_type> and <cell_type>DCs</cell_type> from humans and mice .


We have used immunolabeling , Western blot analysis , and electrophoretic mobility shift and supershift assays .


T cells lack active NF-kappa B but express Sp1 as expected .

<cell_type>T cells</cell_type> lack active <protein>NF-kappa B</protein> but express <protein>Sp1</protein> as expected .


DCs express high levels of all known NF-kappa B and Rel proteins , with activity residing primarily within RelB , p50 , and p65 .

<cell_type>DCs</cell_type> express high levels of all known <protein>NF-kappa B</protein> and <protein>Rel proteins</protein> , with activity residing primarily within <protein>RelB</protein> , <protein>p50</protein> , and <protein>p65</protein> .


However , DCs lack Sp1 , which may explain the failure of HIV-1 to replicate in purified DCs .

However , <cell_type>DCs</cell_type> lack <protein>Sp1</protein> , which may explain the failure of HIV-1 to replicate in purified <cell_type>DCs</cell_type> .


Coexpression of NF-kappa B and Sp1 occurs in the heterologous DC-T-cell syncytia that are induced by HIV-1 .

Coexpression of <protein>NF-kappa B</protein> and <protein>Sp1</protein> occurs in the <cell_type>heterologous DC-T-cell syncytia</cell_type> that are induced by HIV-1 .


Therefore , HIV-1-induced cell fusion brings together factors that upregulate virus transcription .


Since DCs and memory T cells frequently traffic together in situ , these unusual heterologous syncytia could develop in infected individuals and lead to chronic HIV-1 replication without ostensible immune stimulation .

Since <cell_type>DCs</cell_type> and memory <cell_type>T cells</cell_type> frequently traffic together in situ , these unusual <cell_type>heterologous syncytia</cell_type> could develop in infected individuals and lead to chronic HIV-1 replication without ostensible immune stimulation .


Cupric ion blocks NF kappa B activation through inhibiting the signal-induced phosphorylation of I kappa B alpha .

Cupric ion blocks <protein>NF kappa B</protein> activation through inhibiting the signal-induced phosphorylation of <protein>I kappa B alpha</protein> .


A transcription factor NF kappa B , which regulates expression of various cellular genes involved in immune responses and viral genes including HIV , is sequestered in the cytoplasm as a complex with an inhibitory protein I kappa B .

A <protein>transcription factor</protein> <protein>NF kappa B</protein> , which regulates expression of various cellular genes involved in immune responses and <dna>viral genes</dna> including HIV , is sequestered in the cytoplasm as a complex with an <protein>inhibitory protein I kappa B</protein> .


Various extracellular signals induce phosphorylation and rapid degradation of I kappa B alpha to release NF kappa B .

Various extracellular signals induce phosphorylation and rapid degradation of <protein>I kappa B alpha</protein> to release <protein>NF kappa B</protein> .


Cu2+ was found to inhibit the activation of NF kappa B induced by TNF-alpha , TPA , or H2O2 .

Cu2+ was found to inhibit the activation of <protein>NF kappa B</protein> induced by <protein>TNF-alpha</protein> , TPA , or H2O2 .


Deoxycholate treatment of the cytoplasmic extract prepared from cells stimulated by TNF-alpha in the presence of Cu2+ resulted in the release of NF kappa B from I kappa B alpha , indicating that Cu2+ interferes with the dissociation of the NF kappa B-I kappa B complex .

Deoxycholate treatment of the cytoplasmic extract prepared from cells stimulated by <protein>TNF-alpha</protein> in the presence of Cu2+ resulted in the release of <protein>NF kappa B</protein> from <protein>I kappa B alpha</protein> , indicating that Cu2+ interferes with the dissociation of the <protein>NF kappa B-I kappa B complex</protein> .


Neither phosphorylation nor degradation of I kappa B alpha was observed upon TNF-alpha stimulation in the presence of Cu2+ .

Neither phosphorylation nor degradation of <protein>I kappa B alpha</protein> was observed upon <protein>TNF-alpha</protein> stimulation in the presence of Cu2+ .


These results indicate that Cu2+ inhibits the release of NF kappa B by blockade of a signal leading to the phosphorylation of I kappa B alpha .

These results indicate that Cu2+ inhibits the release of <protein>NF kappa B</protein> by blockade of a signal leading to the phosphorylation of <protein>I kappa B alpha</protein> .


Cloning a cDNA from human NK/T cells which codes for a protein with high proline content .

Cloning a <dna>cDNA</dna> from human <cell_type>NK/T cells</cell_type> which codes for a protein with high proline content .


A cDNA clone , B4-2 , was isolated from a natural killer ( NK ) minus T cell subtractive library .

A <dna>cDNA clone</dna> , <dna>B4-2</dna> , was isolated from a <dna>natural killer ( NK ) minus T cell subtractive library</dna> .


The B4-2 clone coded for an mRNA of 2061 bp in length .

The <dna>B4-2</dna> clone coded for an <rna>mRNA</rna> of 2061 bp in length .


It encodes a deduced 327 aa protein with a calculated molecular mass of 35.2 kDa .

It encodes a deduced <protein>327 aa protein</protein> with a calculated molecular mass of 35.2 kDa .


Searching of B4-2 DNA and protein sequences against various databases revealed no high homology to other sequences .

Searching of <dna>B4-2 DNA</dna> and protein sequences against various databases revealed no high homology to other sequences .


However , B4-2 has an unusually high proline content ( 13 % ) , contains a putative nuclear targeting sequence , and has several SPXX motifs which are frequently found in gene regulatory proteins .

However , <dna>B4-2</dna> has an unusually high proline content ( 13 % ) , contains a putative <protein>nuclear targeting sequence</protein> , and has several <protein>SPXX motifs</protein> which are frequently found in <protein>gene regulatory proteins</protein> .


One of the stretches of prolines in B4-2 closely resembles the ligand for proteins with SH3 domains .

One of the stretches of prolines in <dna>B4-2</dna> closely resembles the ligand for proteins with <protein>SH3 domains</protein> .


Northern hybridization data showed that B4-2 is not a lymphoid specific gene and is expressed in a hepatoma cell line and also weakly transcribed or absent in a variety of other cells .

Northern hybridization data showed that <dna>B4-2</dna> is not a <dna>lymphoid specific gene</dna> and is expressed in a <cell_line>hepatoma cell line</cell_line> and also weakly transcribed or absent in a variety of other cells .


A polyclonal antiserum raised against recombinant B4-2 recognizes a 32-34 kDa protein in lymphocytes .

A polyclonal antiserum raised against <protein>recombinant B4-2</protein> recognizes a <protein>32-34 kDa protein</protein> in <cell_type>lymphocytes</cell_type> .