Moreover , there is no cooperation or synergy between R and EB1 when activating the B domain ( ZRE-B plus the R-responsive element ) positioned as an enhancer .

Moreover , there is no cooperation or synergy between <protein>R</protein> and <protein>EB1</protein> when activating the <dna>B domain</dna> ( <dna>ZRE-B</dna> plus the <dna>R-responsive element</dna> ) positioned as an <dna>enhancer</dna> .


ZRE-B is therefore not part of the R- inducible enhancer .

<dna>ZRE-B</dna> is therefore not part of the <dna>R- inducible enhancer</dna> .


We have tested several subregions of the DR enhancer B domain , either alone or in combination , for their capacity to transmit the R-activating signal to the rabbit beta-globin promoter .

We have tested several subregions of the <dna>DR enhancer</dna> <dna>B domain</dna> , either alone or in combination , for their capacity to transmit the R-activating signal to the <dna>rabbit beta-globin promoter</dna> .


We found that the R-responsive element is composed of four protoenhancers that span the whole B domain .

We found that the <dna>R-responsive element</dna> is composed of four <dna>protoenhancers</dna> that span the whole <dna>B domain</dna> .


These protoenhancers alone are weakly or not responsive to R .

These <dna>protoenhancers</dna> alone are weakly or not responsive to <protein>R</protein> .


One of the protoenhancers contains the overlapping palindromes 5'-TTGTCCcgtGGACAAaTGTCC-3' .

One of the <dna>protoenhancers</dna> contains the <dna>overlapping palindromes</dna> 5'-TTGTCCcgtGGACAAaTGTCC-3' .


However , one palindrome , either alone or duplicated , or the overlapping palindromes did not respond to R .

However , one <dna>palindrome</dna> , either alone or duplicated , or the <dna>overlapping palindromes</dna> did not respond to R .


Nuclear 3 , 5 , 3'-triiodothyronine receptors ( T3R ) of circulating human lymphocytes in hyper- and hypothyroidism and nonthyroidal diseases .

Nuclear <protein>3 , 5 , 3'-triiodothyronine receptors</protein> ( <protein>T3R</protein> ) of <cell_type>circulating human lymphocytes</cell_type> in hyper- and hypothyroidism and nonthyroidal diseases .


The clinical implications of nuclear T3R alterations of circulating lymphocytes in hyperthyroidism , hypothyroidism and nonthyroidal diseases were investigated .

The clinical implications of nuclear <protein>T3R</protein> alterations of <cell_type>circulating lymphocytes</cell_type> in hyperthyroidism , hypothyroidism and nonthyroidal diseases were investigated .


Nuclear T3R in lymphocytes was determined by radio-ligand binding analysis .

Nuclear <protein>T3R</protein> in <cell_type>lymphocytes</cell_type> was determined by radio-ligand binding analysis .


The results showed that in hyper- and hypothyroid patients the nuclear affinity ( Ka ) for T3 was similar to that of normal subjects .


In hyperthyroidism nuclear T3 maximal binding capacity ( MBC ) was unaltered , whereas in hypothyroidism the MBC was significantly increased .


In the patients with diabetes mellitus , chronic renal failure and hepatic cirrhosis , the nuclear T3R MBC of lymphocytes was about 1.5-1.6 times of the normal controls .

In the patients with diabetes mellitus , chronic renal failure and hepatic cirrhosis , the <protein>nuclear T3R</protein> MBC of <cell_type>lymphocytes</cell_type> was about 1.5-1.6 times of the normal controls .


It was concluded that there existed hormonal regulation of nuclear T3R , and up-regulation was seen in hypothyroidism and low T3 syndrome .

It was concluded that there existed hormonal regulation of <protein>nuclear T3R</protein> , and up-regulation was seen in hypothyroidism and low T3 syndrome .


Lymphocyte cell lines from vitamin D-dependent rickets type II show functional defects in the 1 alpha , 25-dihydroxyvitamin D3 receptor .

<cell_line>Lymphocyte cell lines</cell_line> from vitamin D-dependent rickets type II show functional defects in the <protein>1 alpha , 25-dihydroxyvitamin D3 receptor</protein> .


Lymphocyte cell lines were established from five patients with vitamin D-dependent rickets , type II ( VDDR-II ) .

<cell_line>Lymphocyte cell lines</cell_line> were established from five patients with vitamin D-dependent rickets , type II ( VDDR-II ) .


These lines were established by infection with human T-lymphotrophic virus type I ( HTLV-I ) .


Binding of [ 3H ] 1 alpha , 25-dihydroxyvitamin D3 ( 1 , 25 ( OH ) 2D3 ) to its receptor in these cell lines was compared to binding studies using a T-lymphocyte cell line ( S-LB1 ) from a normal individual .

Binding of [ 3H ] 1 alpha , 25-dihydroxyvitamin D3 ( 1 , 25 ( OH ) 2D3 ) to its receptor in these cell lines was compared to binding studies using a <cell_line>T-lymphocyte cell line</cell_line> ( <cell_line>S-LB1</cell_line> ) from a normal individual .


The 1 , 25 ( OH ) 2D3 receptor of S-LB1 was comparable to the well-characterized chick intestinal 1 , 25 ( OH ) 2D3 receptor in terms of its ligand binding affinity and capacity , its mobility on 5-20 % sucrose gradients , and its adsorption to and elution properties from DNA-cellulose .

The 1 , 25 ( OH ) 2D3 receptor of <cell_line>S-LB1</cell_line> was comparable to the well-characterized <protein>chick intestinal 1 , 25 ( OH ) 2D3 receptor</protein> in terms of its ligand binding affinity and capacity , its mobility on 5-20 % sucrose gradients , and its adsorption to and elution properties from DNA-cellulose .


Three cell lines established from patients with VDDR-II ( Rh- VDR , Sh- VDR , and Ab- VDR ) showed no specific binding of 1 , 25 ( OH ) 2D3 to a receptor and treatment of the cultured cells with 1 , 25 ( OH ) 2D3 did not stimulate production of 24 , 25-dihydroxy-vitamin D3 ( 24 , 25 ( OH ) 2D3 ) , a response which is diagnostic of the presence of a functional 1 , 25 ( OH ) 2D3 receptor .

Three <cell_line>cell lines</cell_line> established from patients with VDDR-II ( Rh- <protein>VDR</protein> , Sh- <protein>VDR</protein> , and Ab- <protein>VDR</protein> ) showed no specific binding of 1 , 25 ( OH ) 2D3 to a <protein>receptor</protein> and treatment of the <cell_line>cultured cells</cell_line> with 1 , 25 ( OH ) 2D3 did not stimulate production of 24 , 25-dihydroxy-vitamin D3 ( 24 , 25 ( OH ) 2D3 ) , a response which is diagnostic of the presence of a <protein>functional 1 , 25 ( OH ) 2D3 receptor</protein> .


In a fourth cell line , A1-VDR , the receptor for 1 , 25 ( OH ) 2D3 had a low binding capacity and 25 ( OH ) D3-24-hydroxylase activity was not detectable .

In a fourth <cell_line>cell line</cell_line> , <cell_line>A1-VDR</cell_line> , the receptor for 1 , 25 ( OH ) 2D3 had a low binding capacity and <protein>25 ( OH ) D3-24-hydroxylase</protein> activity was not detectable .


Induction of 24 , 25- ( OH ) 2D3 synthesis by 1 , 25 ( OH ) 2D3 was observed in the fifth cell line , designated Ro-VDR , although the sensitivity to hormone treatment was lower than in the control cell line from a normal donor .

Induction of 24 , 25- ( OH ) 2D3 synthesis by 1 , 25 ( OH ) 2D3 was observed in the fifth <cell_line>cell line</cell_line> , designated <cell_line>Ro-VDR</cell_line> , although the sensitivity to hormone treatment was lower than in the <cell_line>control cell line</cell_line> from a normal donor .


The capacity of the receptor for 1 , 25 ( OH ) 2D3 was low in Ro-VDR .

The capacity of the <protein>receptor</protein> for 1 , 25 ( OH ) 2D3 was low in <cell_line>Ro-VDR</cell_line> .


In all cell lines where 1 , 25 ( OH ) 2D3 binding to a receptor was detectable , the receptor had the typical sedimentation coefficient of 3.7 S on sucrose density gradient analysis .

In all <cell_line>cell lines</cell_line> where 1 , 25 ( OH ) 2D3 binding to a <protein>receptor</protein> was detectable , the <protein>receptor</protein> had the typical sedimentation coefficient of 3.7 S on sucrose density gradient analysis .


Binding and elution properties to DNA-cellulose , however , differed from normal in both Ro-VDR and A1-VDR cells where elution from DNA-cellulose occurred at a lower salt concentration than is typical of the 1 , 25 ( OH ) 2D3 receptor .

Binding and elution properties to DNA-cellulose , however , differed from normal in both <cell_line>Ro-VDR</cell_line> and <cell_line>A1-VDR cells</cell_line> where elution from DNA-cellulose occurred at a lower salt concentration than is typical of the <protein>1 , 25 ( OH ) 2D3 receptor</protein> .


While Ro-VDR cells showed typical nuclear localization of the unoccupied 1 , 25 ( OH ) 2D3 receptor , neither the unoccupied nor the occupied receptor from A1-VDR cells was completely localized in the nucleus .

While <cell_line>Ro-VDR cells</cell_line> showed typical nuclear localization of the <protein>unoccupied 1 , 25 ( OH ) 2D3 receptor</protein> , neither the unoccupied nor the occupied <protein>receptor</protein> from <cell_line>A1-VDR cells</cell_line> was completely localized in the nucleus .


In a series of functional studies we found that modulation of the level of the mRNAs coding for both the c-myc oncogene and the growth factor known as granulocyte-monocyte colony stimulating activity by 1 , 25 ( OH ) 2D3 correlated with the 1 , 25 ( OH ) 2D3 receptor status of these cells .

In a series of functional studies we found that modulation of the level of the <rna>mRNAs</rna> coding for both the <dna>c-myc oncogene</dna> and the growth factor known as granulocyte-monocyte colony stimulating activity by 1 , 25 ( OH ) 2D3 correlated with the <protein>1 , 25 ( OH ) 2D3 receptor</protein> status of these cells .


Use of these cell lines will facilitate further study of the molecular defect ( s ) in the receptor for 1 , 25 ( OH ) 2D3 in vitamin D-dependent rickets type II and will allow a correlation with impairment of cellular functions .

Use of these <cell_line>cell lines</cell_line> will facilitate further study of the molecular defect ( s ) in the <protein>receptor</protein> for 1 , 25 ( OH ) 2D3 in vitamin D-dependent rickets type II and will allow a correlation with impairment of cellular functions .


Transcriptional and post-transcriptional regulation of c-jun expression during monocytic differentiation of human myeloid leukemic cells .

Transcriptional and post-transcriptional regulation of <dna>c-jun</dna> expression during monocytic differentiation of <cell_line>human myeloid leukemic cells</cell_line> .


AP-1 , the polypeptide product of c-jun , recognizes and binds to specific DNA sequences and stimulates transcription of genes responsive to certain growth factors and phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate ( TPA ) .

<protein>AP-1</protein> , the polypeptide product of <dna>c-jun</dna> , recognizes and binds to specific DNA sequences and stimulates transcription of <dna>genes</dna> responsive to certain growth factors and phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate ( TPA ) .


We studied the effects of TPA on the regulation of c-jun gene expression in HL-60 cells during monocytic differentiation .

We studied the effects of TPA on the regulation of <dna>c-jun</dna> gene expression in <cell_line>HL-60 cells</cell_line> during monocytic differentiation .


Low levels of c-jun transcripts were detectable in untreated HL-60 leukemic cells , increased significantly by 6 h , and reached near maximal levels by 24 h of exposure to 32 nM TPA .

Low levels of <rna>c-jun transcripts</rna> were detectable in <cell_line>untreated HL-60 leukemic cells</cell_line> , increased significantly by 6 h , and reached near maximal levels by 24 h of exposure to 32 nM TPA .


Similar kinetics of c-jun induction by TPA were observed in human U-937 and THP-1 monocytic leukemia cells .

Similar kinetics of <dna>c-jun</dna> induction by TPA were observed in <cell_line>human U-937</cell_line> and <cell_line>THP-1 monocytic leukemia cells</cell_line> .


Similar findings were obtained with bryostatin 1 ( 10 nM ) , another activator of protein kinase C and inducer of monocytic differentiation .

Similar findings were obtained with bryostatin 1 ( 10 nM ) , another activator of <protein>protein kinase C</protein> and inducer of monocytic differentiation .


Furthermore , 1 , 25-dihydroxyvitamin D3 ( 0.5 microM ) , a structurally distinct agent which also induces HL-60 monocytic differentiation , increased c-jun expression .

Furthermore , 1 , 25-dihydroxyvitamin D3 ( 0.5 microM ) , a structurally distinct agent which also induces HL-60 monocytic differentiation , increased <dna>c-jun</dna> expression .


TPA treatment of HL-60 cells in the presence of cycloheximide was associated with superinduction of c-jun transcripts .

TPA treatment of <cell_line>HL-60 cells</cell_line> in the presence of cycloheximide was associated with superinduction of <dna>c-jun</dna> transcripts .


Run-on analysis demonstrated detectable levels of c-jun gene transcription in untreated HL-60 cells , and that exposure to TPA increases this rate 3.3-fold .

Run-on analysis demonstrated detectable levels of <dna>c-jun</dna> gene transcription in <cell_line>untreated HL-60 cells</cell_line> , and that exposure to TPA increases this rate 3.3-fold .


Treatment of HL-60 cells with both TPA and cycloheximide had no effect on the rates of c-jun transcription .

Treatment of <cell_line>HL-60 cells</cell_line> with both TPA and cycloheximide had no effect on the rates of <dna>c-jun</dna> transcription .


The half-life of c-jun RNA as determined by treating HL-60 cells with TPA and actinomycin D was 30 min .

The half-life of <rna>c-jun RNA</rna> as determined by treating <cell_line>HL-60 cells</cell_line> with TPA and actinomycin D was 30 min .


In contrast , the half-life of c-jun RNA in TPA-treated HL-60 cells exposed to cycloheximide and actinomycin D was greater than 2 h .

In contrast , the half-life of <rna>c-jun RNA</rna> in <cell_line>TPA-treated HL-60 cells</cell_line> exposed to cycloheximide and actinomycin D was greater than 2 h .


These findings suggested that the increase in c-jun RNA observed during TPA-induced monocytic differentiation is mediated by both transcriptional and post-transcriptional mechanisms .

These findings suggested that the increase in <rna>c-jun RNA</rna> observed during TPA-induced monocytic differentiation is mediated by both transcriptional and post-transcriptional mechanisms .


[ Hormonal interactions and glucocorticoid receptors in patients with the nephrotic syndrome ]

[ Hormonal interactions and <protein>glucocorticoid receptors</protein> in patients with the nephrotic syndrome ]


As many as 27 children aged 6 to 15 years with morphologically verified nephropathies were examined .


Four variants of changes in the thyroid status , characteristic of children with different variants of nephrotic syndrome were distinguished : 1 ) biochemical signs of primary hypothyroidism , 2 ) biochemical signs of secondary hypothyroidism , 3 ) low content of T3 , 4 ) dysfunction of the hypophyseal and thyroid system .


It is shown that the low level of steroid receptors , thyroid hormones that the low level of steroid receptors , thyroid hormones ( T3 and T4 ) and cortisol is typical of children with the signs of renal dysplasia .

It is shown that the low level of <protein>steroid receptors</protein> , thyroid hormones that the low level of <protein>steroid receptors</protein> , thyroid hormones ( T3 and T4 ) and cortisol is typical of children with the signs of renal dysplasia .


It is assumed that superaddition under such conditions of immune glomerulopathy ( glomerulonephritis and nephrotic syndrome ) gives rise to the resistance to the treatment with glucocorticoids .


Lymphoid specific gene expression of the adenovirus early region 3 promoter is mediated by NF-kappa B binding motifs .

Lymphoid specific gene expression of the <dna>adenovirus early region 3 promoter</dna> is mediated by <dna>NF-kappa B binding motifs</dna> .


A primary site of infection by human adenoviruses is lymphoid cells .

A primary site of infection by human adenoviruses is <cell_type>lymphoid cells</cell_type> .


However , analysis of the viral control elements and the cellular factors that regulate adenoviral gene expression in lymphocytes has not been reported .

However , analysis of the <dna>viral control elements</dna> and the <protein>cellular factors</protein> that regulate adenoviral gene expression in <cell_type>lymphocytes</cell_type> has not been reported .


The adenovirus early region 3 ( ES ) gene products are involved in the maintenance of viral persistence by complexing with the class I MHC antigens , thus preventing their cell surface expression with a resultant decrease in host immunologic destruction .

The <protein>adenovirus early region 3 ( ES ) gene products</protein> are involved in the maintenance of viral persistence by complexing with the <protein>class I MHC antigens</protein> , thus preventing their cell surface expression with a resultant decrease in host immunologic destruction .


To determine whether different cellular factors were involved in E3 regulation in lymphocytes as compared with HeLa cells , both DNA binding and transfection analysis with the E3 promoter in both cell types were performed .

To determine whether different <protein>cellular factors</protein> were involved in E3 regulation in <cell_type>lymphocytes</cell_type> as compared with <cell_line>HeLa cells</cell_line> , both DNA binding and transfection analysis with the <dna>E3 promoter</dna> in both cell types were performed .


These studies detected two novel domains referred to as L1 and L2 with a variety of lymphoid but not HeLa extracts .

These studies detected two <dna>novel domains</dna> referred to as <dna>L1</dna> and <dna>L2</dna> with a variety of lymphoid but not HeLa extracts .


Each of these domains possessed strong homology to motifs previously found to bind the cellular factor NF-kappa B .

Each of these domains possessed strong homology to motifs previously found to bind the <protein>cellular factor NF-kappa B</protein> .


Transfections of E3 constructs linked to the chloramphenicol acetyltransferase gene revealed that mutagenesis of the distal NF-kappa B motif ( L2 ) had minimal effects on promoter expression in HeLa cells , but resulted in dramatic decreases in expression by lymphoid cells .

Transfections of <dna>E3 constructs</dna> linked to the <dna>chloramphenicol acetyltransferase gene</dna> revealed that mutagenesis of the <dna>distal NF-kappa B motif</dna> ( <dna>L2</dna> ) had minimal effects on promoter expression in <cell_line>HeLa cells</cell_line> , but resulted in dramatic decreases in expression by <cell_type>lymphoid cells</cell_type> .


In contrast , mutagenesis of proximal NF-kappa B motif ( L1 ) had minimal effects on gene expression in both HeLa cells and lymphoid cells but resulted in a small , but reproducible , increase in gene expression in lymphoid cells when coupled to the L2 mutation .

In contrast , mutagenesis of <dna>proximal NF-kappa B motif</dna> ( <dna>L1</dna> ) had minimal effects on gene expression in both <cell_line>HeLa cells</cell_line> and <cell_type>lymphoid cells</cell_type> but resulted in a small , but reproducible , increase in gene expression in <cell_type>lymphoid cells</cell_type> when coupled to the <dna>L2</dna> mutation .


Reversing the position and subsequent mutagenesis of the L1 and L2 domains indicated that the primary sequence of these motifs rather than their position in the E3 promoter was critical for regulating gene expression .

Reversing the position and subsequent mutagenesis of the <dna>L1</dna> and <dna>L2 domains</dna> indicated that the <dna>primary sequence</dna> of these motifs rather than their position in the <dna>E3 promoter</dna> was critical for regulating gene expression .


( ABSTRACT TRUNCATED AT 250 WORDS )


Characterization of defensin resistance phenotypes associated with mutations in the phoP virulence regulon of Salmonella typhimurium .

Characterization of <protein>defensin</protein> resistance phenotypes associated with mutations in the <dna>phoP virulence regulon</dna> of Salmonella typhimurium .


The defensin sensitivities of Salmonella typhimurium strains with mutations in the phoP/phoQ two-component virulence regulon were tested by using purified defensins NP-1 and NP-2 .

The <protein>defensin</protein> sensitivities of Salmonella typhimurium strains with mutations in the <dna>phoP/phoQ two-component virulence regulon</dna> were tested by using <protein>purified defensins</protein> <protein>NP-1</protein> and <protein>NP-2</protein> .


Strains with mutations in either gene of the regulatory pair ( phoP [ transcriptional activator ] or phoQ [ membrane sensor kinase ] ) had increased sensitivities to defensin .

Strains with mutations in either gene of the <dna>regulatory pair</dna> ( <dna>phoP</dna> [ <dna>transcriptional activator</dna> ] or <dna>phoQ</dna> [ <protein>membrane sensor kinase</protein> ] ) had increased sensitivities to <protein>defensin</protein> .


The predicted periplasmic domain of the PhoQ protein contained a markedly anionic domain that could interact with cationic proteins and that could be responsible for resistance to defensin .

The predicted <protein>periplasmic domain</protein> of the <protein>PhoQ protein</protein> contained a markedly anionic domain that could interact with <protein>cationic proteins</protein> and that could be responsible for resistance to <protein>defensin</protein> .


Because insertion mutations in phoP are polar on phoQ , we constructed strains that expressed the PhoQ protein in the absence of PhoP to test whether resistance to defensin requires only the phoQ gene product .

Because insertion mutations in <dna>phoP</dna> are polar on <dna>phoQ</dna> , we constructed strains that expressed the <protein>PhoQ protein</protein> in the absence of <protein>PhoP</protein> to test whether resistance to defensin requires only the <protein>phoQ gene product</protein> .


We found that resistance to defensin requires the function of both components of this regulatory system , because strains expressing PhoQ without PhoP were still markedly sensitive to defensins .

We found that resistance to defensin requires the function of both components of this regulatory system , because strains expressing <protein>PhoQ</protein> without <protein>PhoP</protein> were still markedly sensitive to <protein>defensins</protein> .


This implied that a pag ( phoP-activated gene ) product is responsible for defensin resistance .

This implied that a <protein>pag ( phoP-activated gene ) product</protein> is responsible for <protein>defensin</protein> resistance .


We also tested for the ability of defensins NP-1 , NP-5 , and HNP-1 to activate pag expression and found that these peptides have no effect .

We also tested for the ability of <protein>defensins</protein> <protein>NP-1</protein> , <protein>NP-5</protein> , and <protein>HNP-1</protein> to activate <dna>pag</dna> expression and found that these peptides have no effect .


Defensin resistance is not the only virulence characteristic controlled by the PhoP-PhoQ regulon because mutations in pagC , as well as ones in the phoP locus that resulted in constitutive pag activation ( phenotype PhoPc ) , had no effect on defensin resistance , even though they rendered the organism avirulent and deficient in survival within macrophages .

Defensin resistance is not the only virulence characteristic controlled by the <protein>PhoP-PhoQ regulon</protein> because mutations in <dna>pagC</dna> , as well as ones in the <dna>phoP locus</dna> that resulted in constitutive <dna>pag</dna> activation ( phenotype <protein>PhoPc</protein> ) , had no effect on <protein>defensin</protein> resistance , even though they rendered the organism avirulent and deficient in survival within <cell_type>macrophages</cell_type> .


The virulence defect conferred by mutations in the phoP -phoQ two-component regulatory system is not completely explained by alterations in resistance to cationic proteins and involves the control of other proteins necessary for S. typhimurium survival within macrophages .

The virulence defect conferred by mutations in the <dna>phoP</dna> <dna>-phoQ</dna> two-component regulatory system is not completely explained by alterations in resistance to <protein>cationic proteins</protein> and involves the control of other proteins necessary for S. typhimurium survival within <cell_type>macrophages</cell_type> .


Stimulation of a human T-cell clone with anti-CD3 or tumor necrosis factor induces NF-kappa B translocation but not human immunodeficiency virus 1 enhancer-dependent transcription .

Stimulation of a <cell_line>human T-cell clone</cell_line> with <protein>anti-CD3</protein> or <protein>tumor necrosis factor</protein> induces <protein>NF-kappa B</protein> translocation but not human immunodeficiency virus 1 enhancer-dependent transcription .


The expression of transiently transfected expression vectors under the control of the long terminal repeat ( LTR ) of the human immunodeficiency virus ( HIV ) or its enhancer sequence and the translocation of the HIV enhancer-binding protein NF-kappa B were analyzed in two human T-cell clones stimulated through their T-cell receptor complex or by tumor necrosis factor or phorbol 12-myristate 13-acetate .

The expression of transiently transfected expression vectors under the control of the <dna>long terminal repeat</dna> ( <dna>LTR</dna> ) of the human immunodeficiency virus ( HIV ) or its <dna>enhancer sequence</dna> and the translocation of the <protein>HIV enhancer-binding protein</protein> <protein>NF-kappa B</protein> were analyzed in two human <cell_line>T-cell clones</cell_line> stimulated through their <protein>T-cell receptor complex</protein> or by <protein>tumor necrosis factor</protein> or phorbol 12-myristate 13-acetate .


We found a dissociation of NF-kappa B translocation from transactivation of either the HIV LTR or the HIV enhancer .

We found a dissociation of <protein>NF-kappa B</protein> translocation from transactivation of either the <dna>HIV LTR</dna> or the <dna>HIV enhancer</dna> .


Interleukin 2 induced proliferation but not NF-kappa B translocation or LTR transactivation .

<protein>Interleukin 2</protein> induced proliferation but not <protein>NF-kappa B</protein> translocation or <dna>LTR</dna> transactivation .


Phorbol ester or specific antigen recognition induced HIV LTR transactivation , whereas stimulation with tumor necrosis factor or antibody to CD3 did not .

Phorbol ester or specific antigen recognition induced <dna>HIV LTR</dna> transactivation , whereas stimulation with <protein>tumor necrosis factor</protein> or antibody to <protein>CD3</protein> did not .


The two latter signals were nevertheless able to induce NF-kappa B translocation with a pattern in the band-shift assay indistinguishable from that observed using phorbol ester .

The two latter signals were nevertheless able to induce <protein>NF-kappa B</protein> translocation with a pattern in the band-shift assay indistinguishable from that observed using phorbol ester .


Our finding that induction of NF-kappa B by tumor necrosis factor or antibody to CD3 is not sufficient to induce HIV enhancer -dependent transcription in cloned T cells contrasts with results obtained in most lymphoblastoid T-cell lines and indicates that normal T lymphocytes differ from tumoral T cells in terms of requirements for HIV LTR activation .

Our finding that induction of <protein>NF-kappa B</protein> by <protein>tumor necrosis factor</protein> or <protein>antibody to CD3</protein> is not sufficient to induce <dna>HIV enhancer</dna> -dependent transcription in <cell_line>cloned T cells</cell_line> contrasts with results obtained in most <cell_line>lymphoblastoid T-cell lines</cell_line> and indicates that normal <cell_type>T lymphocytes</cell_type> differ from <cell_type>tumoral T cells</cell_type> in terms of requirements for <dna>HIV LTR</dna> activation .


Furthermore , our results suggest that events linked to T-cell activation , in addition to NF-kappa B translocation per se , induce functional interactions of the NF-kappa B complex with the HIV enhancer .

Furthermore , our results suggest that events linked to T-cell activation , in addition to <protein>NF-kappa B</protein> translocation per se , induce functional interactions of the <protein>NF-kappa B complex</protein> with the <dna>HIV enhancer</dna> .


Decreased concentration of 1 , 25-dihydroxyvitamin D3 receptors in peripheral mononuclear cells of patients with X-linked hypophosphatemic rickets : effect of phosphate supplementation .

Decreased concentration of <protein>1 , 25-dihydroxyvitamin D3 receptors</protein> in <cell_type>peripheral mononuclear cells</cell_type> of patients with X-linked hypophosphatemic rickets : effect of phosphate supplementation .


Abnormal renal tubular phosphate transport is considered to be the primary defect in X-linked hypophosphatemic rickets ( XLH ) .


However , the resistance to vitamin D treatment in XLH can not be explained by hypophosphatemia alone .


Since most of the actions of vitamin D are mediated by its receptors ( VDR ) , abnormalities of VDR have been postulated in XLH .

Since most of the actions of vitamin D are mediated by its receptors ( <protein>VDR</protein> ) , abnormalities of <protein>VDR</protein> have been postulated in XLH .


In order to investigate this possibility , we measured the concentration of VDR in PHA-activated peripheral mononuclear cells from 10 XLH patients .

In order to investigate this possibility , we measured the concentration of <protein>VDR</protein> in <cell_line>PHA-activated peripheral mononuclear cells</cell_line> from 10 XLH patients .


Patients without phosphate supplementation showed significantly lower concentration ( 21.7 +/- 5.1 fmol/mg protein , mean +/- SEM ) compared to the normal controls ( 60.7 +/- 4.0 ) .


On the contrary , there was no significant difference between the phosphate-supplemented patients ( 58.3 +/- 2.7 ) and controls .


There was a significant positive correlation between VDR concentration and serum phosphate ( P less than 0.05 ) .

There was a significant positive correlation between <protein>VDR</protein> concentration and serum phosphate ( P less than 0.05 ) .


In two patients , VDR was increased after daily phosphate supplementation was started .

In two patients , <protein>VDR</protein> was increased after daily phosphate supplementation was started .


These results indicate that a decreased concentration of VDR secondary to persistent hypophosphatemia is one of the causes of vitamin D resistance in XLH .

These results indicate that a decreased concentration of <protein>VDR</protein> secondary to persistent hypophosphatemia is one of the causes of vitamin D resistance in XLH .


Two distinct forms of active transcription factor CREB ( cAMP response element binding protein ) .

Two distinct forms of <protein>active transcription factor CREB</protein> ( <protein>cAMP response element binding protein</protein> ) .


Mammalian cells express two distinct forms of transcription factor CREB ( cAMP response element binding protein ) that are apparently the products of alternative splicing of the CREB gene transcript .

<cell_type>Mammalian cells</cell_type> express two distinct forms of <protein>transcription factor CREB</protein> ( <protein>cAMP response element binding protein</protein> ) that are apparently the products of alternative splicing of the <rna>CREB gene transcript</rna> .


The two proteins differ by a 14-amino acid serine-rich insertion present in one of the CREB isoforms .

The two proteins differ by a <protein>14-amino acid serine-rich insertion</protein> present in one of the <protein>CREB isoforms</protein> .


We show that both CREB isoforms are expressed in many cell types and mammalian species .

We show that both <protein>CREB isoforms</protein> are expressed in <cell_type>many cell types</cell_type> and mammalian species .


Both encode proteins that bind specifically to a cAMP response element in vitro .

Both encode proteins that bind specifically to a <dna>cAMP response element in vitro</dna> .


As expected for proteins of this class , the CREB proteins bind DNA as dimers .

As expected for proteins of this class , the <protein>CREB proteins</protein> bind DNA as dimers .


Both proteins impart cAMP-regulated transcriptional activity to a heterologous DNA-binding domain , showing that cAMP directly modulates the transcriptional stimulatory activity of CREB .

Both proteins impart cAMP-regulated transcriptional activity to a <dna>heterologous DNA-binding domain</dna> , showing that cAMP directly modulates the transcriptional stimulatory activity of <protein>CREB</protein> .


The presence of multiple CREB isoforms with identical DNA-binding specificities but differences in the presumed regulatory domain raises the possibility that CREB proteins may be able to integrate distinct regulatory signals at the level of gene transcription .

The presence of multiple <protein>CREB isoforms</protein> with identical DNA-binding specificities but differences in the presumed <protein>regulatory domain</protein> raises the possibility that <protein>CREB proteins</protein> may be able to integrate distinct regulatory signals at the level of gene transcription .


Human immunodeficiency virus vpr product is a virion-associated regulatory protein .

Human immunodeficiency virus vpr product is a <protein>virion-associated regulatory protein</protein> .


The vpr product of the human immunodeficiency virus type 1 ( HIV-1 ) acts in trans to accelerate virus replication and cytopathic effect in T cells .

The <protein>vpr product</protein> of the human immunodeficiency virus type 1 ( HIV-1 ) acts in trans to accelerate virus replication and cytopathic effect in <cell_type>T cells</cell_type> .


Here it is shown that the HIV-1 viral particle contains multiple copies of the vpr protein .

Here it is shown that the HIV-1 viral particle contains multiple copies of the <protein>vpr protein</protein> .


The vpr product is the first regulatory protein of HIV-1 to be found in the virus particle .

The <protein>vpr product</protein> is the first regulatory protein of HIV-1 to be found in the virus particle .


This observation raises the possibility that vpr acts to facilitate the early steps of infection before de novo viral protein synthesis occurs .

This observation raises the possibility that <dna>vpr</dna> acts to facilitate the early steps of infection before de novo viral protein synthesis occurs .


A novel B-cell lineage-specific transcription factor present at early but not late stages of differentiation .

A novel <protein>B-cell lineage-specific transcription factor</protein> present at early but not late stages of differentiation .


A novel B-cell-specific transcription factor , BSAP , was identified as a mammalian homolog of the sea urchin protein TSAP , which interacts with the promoters of four tissue-specific late histone H2A-2 and H2B-2 genes .

A novel <protein>B-cell-specific transcription factor</protein> , <protein>BSAP</protein> , was identified as a <protein>mammalian homolog</protein> of the <protein>sea urchin protein</protein> <protein>TSAP</protein> , which interacts with the <dna>promoters</dna> of four <dna>tissue-specific late histone H2A-2 and H2B-2 genes</dna> .


As shown by mobility-shift , methylation interference , and mutational analyses , the mammalian protein BSAP recognizes all four sea urchin binding sites in a manner indistinguishable from TSAP ; however , the two proteins differ in molecular weight .

As shown by mobility-shift , methylation interference , and mutational analyses , the <protein>mammalian protein</protein> <protein>BSAP</protein> recognizes all four <dna>sea urchin binding sites</dna> in a manner indistinguishable from <protein>TSAP</protein> ; however , the two proteins differ in molecular weight .


BSAP is exclusively restricted to the B-cell lineage of lymphoid differentiation .

<protein>BSAP</protein> is exclusively restricted to the B-cell lineage of lymphoid differentiation .


Its expression appears to be activated during pro-B-cell development , is abundant at the pre-B- and mature B-cell stages , but is absent in terminally differentiated plasma cells .

Its expression appears to be activated during pro-B-cell development , is abundant at the pre-B- and mature B-cell stages , but is absent in <cell_type>terminally differentiated plasma cells</cell_type> .


Moreover , BSAP is clearly a B-cell-specific transcription factor , as a wild-type but not a mutant TSAP-binding site of the sea urchin functions only in transfected B cells as an upstream promoter element .

Moreover , <protein>BSAP</protein> is clearly a <protein>B-cell-specific transcription factor</protein> , as a <dna>wild-type</dna> but not a <dna>mutant TSAP-binding site</dna> of the sea urchin functions only in <cell_line>transfected B cells</cell_line> as an <dna>upstream promoter element</dna> .


Competition experiments did not reveal any high-affinity binding site for BSAP in known regulatory regions of immunoglobulin and class II major histocompatibility ( MHC ) genes , suggesting that BSAP is a regulator of a different set of B-lymphoid-specific genes .

Competition experiments did not reveal any <dna>high-affinity binding site</dna> for <protein>BSAP</protein> in known <dna>regulatory regions</dna> of <dna>immunoglobulin and class II major histocompatibility ( MHC ) genes</dna> , suggesting that <protein>BSAP</protein> is a regulator of a different set of <dna>B-lymphoid-specific genes</dna> .


Octamer transcription factors and the cell type-specificity of immunoglobulin gene expression .

<protein>Octamer transcription factors</protein> and the <dna>cell type-specificity of immunoglobulin gene</dna> expression .


Antibodies are produced exclusively in B lymphocytes .

<protein>Antibodies</protein> are produced exclusively in <cell_type>B lymphocytes</cell_type> .


The expression of the antibody-encoding genes , the immunoglobulin ( Ig ) genes , is also restricted to B cells .

The expression of the <dna>antibody-encoding genes</dna> , the <dna>immunoglobulin ( Ig ) genes</dna> , is also restricted to <cell_type>B cells</cell_type> .


The octamer sequence ATGCAAAT is present in the promoter and the enhancer of Ig genes , and plays an important role in its tissue-specific expression .

The <dna>octamer sequence</dna> ATGCAAAT is present in the <dna>promoter</dna> and the <dna>enhancer</dna> of <dna>Ig genes</dna> , and plays an important role in its tissue-specific expression .


This sequence motif is a binding site for nuclear proteins , the so-called octamer transcription factors ( Oct or OTF factors ) .

This <dna>sequence motif</dna> is a binding site for <protein>nuclear proteins</protein> , the so-called <protein>octamer transcription factors</protein> ( <protein>Oct</protein> or <protein>OTF factors</protein> ) .


The Oct-1 protein is present in all cell types analyzed so far , whereas Oct-2A and Oct-2B are found mainly in B lymphocytes .

The <protein>Oct-1 protein</protein> is present in all cell types analyzed so far , whereas <protein>Oct-2A</protein> and <protein>Oct-2B</protein> are found mainly in <cell_type>B lymphocytes</cell_type> .


All three proteins show the same sequence specificity and binding affinity .


It appears that the B cell-specific expression of Ig genes is mediated at least in part by cell type-specific Oct factors , and that there are both quantitative and qualitative differences between Oct-1 and Oct-2 factors .

It appears that the B cell-specific expression of <dna>Ig genes</dna> is mediated at least in part by cell <protein>type-specific Oct factors</protein> , and that there are both quantitative and qualitative differences between <protein>Oct-1</protein> and <protein>Oct-2 factors</protein> .


Recently , a number of other octamer factor variants were identified .

Recently , a number of other <protein>octamer factor variants</protein> were identified .


Many of these may be created by alternative splicing of a primary transcript of one Oct factor gene and may serve a specific function in the fine tuning of gene expression .

Many of these may be created by alternative splicing of a <rna>primary transcript</rna> of one Oct factor gene and may serve a specific function in the fine tuning of gene expression .


A factor known to bind to endogenous Ig heavy chain enhancer only in lymphocytes is a ubiquitously active transcription factor .

A factor known to bind to <dna>endogenous Ig heavy chain enhancer</dna> only in <cell_type>lymphocytes</cell_type> is a <protein>ubiquitously active transcription factor</protein> .


The transcriptional enhancer located in the first intron of the immunoglobulin heavy chain constant region is a major determinant of B-cell-specific expression of immunoglobulin genes .

The <dna>transcriptional enhancer</dna> located in the first intron of the <dna>immunoglobulin heavy chain constant region</dna> is a major determinant of B-cell-specific expression of <dna>immunoglobulin genes</dna> .


Like other enhancers , the Ig heavy chain enhancer contains several short sequence motifs that bind specific transcription factors .

Like other <dna>enhancers</dna> , the <dna>Ig heavy chain enhancer</dna> contains several short <dna>sequence motifs</dna> that bind <protein>specific transcription factors</protein> .


Each binding site contributes to the overall activity of the enhancer , however no single element seems absolutely required for activity .

Each <dna>binding site</dna> contributes to the overall activity of the <dna>enhancer</dna> , however no single element seems absolutely required for activity .


For a better understanding of the Ig heavy chain enhancer components , we have cloned and analyzed individual sequence elements .

For a better understanding of the <dna>Ig heavy chain enhancer components</dna> , we have cloned and analyzed individual <dna>sequence elements</dna> .


We find that the factor that binds to the E3 enhancer motif , CATGTGGC , is a ubiquitous transcription factor .

We find that the factor that binds to the <dna>E3 enhancer motif</dna> , CATGTGGC , is a <protein>ubiquitous transcription factor</protein> .


It is present in an active form in both B cells and non-B cells , where it can mediate transcriptional activation in vitro and in vivo .

It is present in an active form in both <cell_type>B cells</cell_type> and <cell_type>non-B cells</cell_type> , where it can mediate transcriptional activation in vitro and in vivo .


However , despite its ability to activate transcription of a transfected reporter gene , the factor is apparently unable to bind to the endogenous Ig heavy chain enhancer in non-lymphoid cells : In previous experiments by others , the characteristic in vivo footprint of this factor , designated NF-muE3 , was detected in B cells but not in non-B cells .

However , despite its ability to activate transcription of a <dna>transfected reporter gene</dna> , the factor is apparently unable to bind to the <dna>endogenous Ig heavy chain enhancer</dna> in <cell_type>non-lymphoid cells</cell_type> : In previous experiments by others , the characteristic in vivo footprint of this factor , designated <protein>NF-muE3</protein> , was detected in <cell_type>B cells</cell_type> but not in <cell_type>non-B cells</cell_type> .


From this and other findings the picture emerges that there are at least three categories of factors which mediate cell-type-specific transcription in B lymphocytes : ( a ) cell-specific factors such as Oct-2A and Oct-2B that are not expressed in most other cell types : ( b ) ubiquitous factors such as NF-kappa B that are constitutively active in B cells but are sequestered in an inactive form in other cells ; ( c ) ubiquitously active factors , exemplified by the one binding to the E3 sequence motif .

From this and other findings the picture emerges that there are at least three categories of factors which mediate cell-type-specific transcription in <cell_type>B lymphocytes</cell_type> : ( a ) <protein>cell-specific factors</protein> such as <protein>Oct-2A</protein> and <protein>Oct-2B</protein> that are not expressed in most other cell types : ( b ) <protein>ubiquitous factors</protein> such as <protein>NF-kappa B</protein> that are constitutively active in <cell_type>B cells</cell_type> but are sequestered in an inactive form in other cells ; ( c ) <protein>ubiquitously active factors</protein> , exemplified by the one binding to the <dna>E3 sequence motif</dna> .


This factor is present in an active form in a variety of cell types but is apparently unable to bind to the endogenous Ig heavy chain enhancer in non-B cells , perhaps due to a non-permissive chromatin structure of the Ig heavy chain locus .

This factor is present in an active form in a variety of cell types but is apparently unable to bind to the <dna>endogenous Ig heavy chain enhancer</dna> in <cell_type>non-B cells</cell_type> , perhaps due to a non-permissive <dna>chromatin</dna> structure of the <dna>Ig heavy chain locus</dna> .


[ Endocrine status changes in children with bronchial asthma ]


A study was made of adrenocortical function by measuring blood plasma cortisol concentration and amount of glucocorticoid receptors in lymphocytes as well as thyroid function by measuring blood plasma triidothyronine and thyroxine concentration in 58 bronchial asthma children aged 1 to 14 years .

A study was made of adrenocortical function by measuring blood plasma cortisol concentration and amount of <protein>glucocorticoid receptors</protein> in <cell_type>lymphocytes</cell_type> as well as thyroid function by measuring blood plasma triidothyronine and thyroxine concentration in 58 bronchial asthma children aged 1 to 14 years .


The authors revealed alterations in the functional activity of the indicated endocrine glands depending on the intensity of bronchial patency disorders and the nature of the therapeutic measures carried out .


TAR independent activation of the human immunodeficiency virus in phorbol ester stimulated T lymphocytes .

<dna>TAR</dna> independent activation of the human immunodeficiency virus in phorbol ester stimulated <cell_type>T lymphocytes</cell_type> .


Multiple regulatory elements in the human immunodeficiency virus long terminal repeat ( HIV LTR ) are required for activation of HIV gene expression .

<dna>Multiple regulatory elements</dna> in the <dna>human immunodeficiency virus long terminal repeat</dna> ( <dna>HIV LTR</dna> ) are required for activation of HIV gene expression .


Previous transfection studies of HIV LTR constructs linked to the chloramphenicol acetyltransferase gene indicated that multiple regulatory regions including the enhancer , SP1 , TATA and TAR regions were important for HIV gene expression .

Previous transfection studies of <dna>HIV LTR constructs</dna> linked to the <dna>chloramphenicol acetyltransferase gene</dna> indicated that multiple <dna>regulatory regions</dna> including the <dna>enhancer</dna> , <dna>SP1</dna> , <dna>TATA</dna> and <dna>TAR regions</dna> were important for HIV gene expression .


To characterize these regulatory elements further , mutations in these regions were inserted into both the 5 ' and 3 ' HIV LTRs and infectious proviral constructs were assembled .

To characterize these <dna>regulatory elements</dna> further , mutations in these regions were inserted into both the 5 ' and 3 ' <dna>HIV LTRs</dna> and infectious proviral constructs were assembled .


These constructs were transfected into either HeLa cells , Jurkat cells or U937 cells in both the presence and absence of phorbol esters which have previously been demonstrated to activate HIV gene expression .

These constructs were transfected into either <cell_line>HeLa cells</cell_line> , <cell_line>Jurkat cells</cell_line> or <cell_line>U937 cells</cell_line> in both the presence and absence of phorbol esters which have previously been demonstrated to activate HIV gene expression .


Viral gene expression was assayed by the level of p24 gag protein released from cultures transfected with the proviral constructs .

Viral gene expression was assayed by the level of <protein>p24 gag protein</protein> released from cultures transfected with the proviral constructs .


Results in all cell lines indicated that mutations of the SP1 , TATA and the TAR loop and stem secondary structure resulted in marked decreases in gene expression while mutations of the enhancer motif or TAR primary sequence resulted in only slight decreases .

Results in all cell lines indicated that mutations of the <dna>SP1</dna> , <dna>TATA</dna> and the TAR loop and stem secondary structure resulted in marked decreases in gene expression while mutations of the <dna>enhancer motif</dna> or <dna>TAR primary sequence</dna> resulted in only slight decreases .


However , viruses containing mutations in either the TAR loop sequences or stem secondary structure which were very defective for gene expression in untreated Jurkat cells , gave nearly wild-type levels of gene expression in phorbol ester-treated Jurkat cells but not in phorbol ester-treated HeLa or U937 cells .

However , viruses containing mutations in either the <dna>TAR loop sequences</dna> or stem secondary structure which were very defective for gene expression in untreated <cell_line>Jurkat cells</cell_line> , gave nearly wild-type levels of gene expression in <cell_line>phorbol ester-treated Jurkat cells</cell_line> but not in <cell_line>phorbol ester-treated HeLa</cell_line> or <cell_line>U937 cells</cell_line> .


High level gene expression of these TAR mutant constructs in phorbol ester-treated Jurkat cells was eliminated by second site mutations in the enhancer region or by disruption of the tat gene .

High level gene expression of these <dna>TAR mutant constructs</dna> in <cell_line>phorbol ester-treated Jurkat cells</cell_line> was eliminated by second site mutations in the <dna>enhancer region</dna> or by disruption of the <dna>tat gene</dna> .


( ABSTRACT TRUNCATED AT 250 WORDS )


A case of hypersensitivity to thyroid hormones with normally functioning thyroid gland and increased nuclear triiodothyronine receptors .

A case of hypersensitivity to thyroid hormones with normally functioning thyroid gland and increased nuclear <protein>triiodothyronine receptors</protein> .


A 52-year-old male presented himself with tachycardia crises which appeared first during childhood , increased in frequency without goiter or exophthalmos .


Cardiac and adrenergic diseases were excluded .


The thyroid function was normal regarding T4 , free T4 and T3 , TBG , radioiodine uptake , TSH and T3 suppressibility ; however the TSH response to TRH was decreased .


The lymphocyte nuclear T3 receptor was found with an affinity close to that of normal volunteers ( Ka : 1.42 x 10 ( 10 ) M-1 vs 1.95 +/- 0.35 x 10 ( 10 ) M-1 ) and a binding capacity markedly increased ( 9.9 vs 3.7 +/- 0.4 fmol T3/100 micrograms DNA ) .

The <protein>lymphocyte nuclear T3 receptor</protein> was found with an affinity close to that of normal volunteers ( Ka : 1.42 x 10 ( 10 ) M-1 vs 1.95 +/- 0.35 x 10 ( 10 ) M-1 ) and a binding capacity markedly increased ( 9.9 vs 3.7 +/- 0.4 fmol T3/100 micrograms DNA ) .


Pindolol was inefficient on the dysrhythmia which disappeared with carbimazole and relapsed after withdrawal of the antithyroid drug .


Under carbimazole , the plasma T4 markedly decreased ( 27.7 +/- 3.6 nmol/l ) but the patient remained euthyroid .


The clinical course and the laboratory data suggest that the tachycardia crises are the consequence of a hypersensitivity of the heart to thyroid hormones , associated with an increased number of T3 nuclear receptor sites in lymphocytes .

The clinical course and the laboratory data suggest that the tachycardia crises are the consequence of a hypersensitivity of the heart to thyroid hormones , associated with an increased number of <protein>T3 nuclear receptor</protein> sites in <cell_type>lymphocytes</cell_type> .


Induction of immediate early response genes by macrophage colony-stimulating factor in normal human monocytes .

Induction of <dna>immediate early response genes</dna> by <protein>macrophage colony-stimulating factor</protein> in <cell_type>normal human monocytes</cell_type> .


A group of coordinately induced protooncogenes , cytoskeletal , and extracellular matrix genes have been termed immediate early response genes , and their induction has been associated with growth factor -stimulated cell proliferation .

A group of coordinately induced <dna>protooncogenes</dna> , <dna>cytoskeletal , and extracellular matrix genes</dna> have been termed <dna>immediate early response genes</dna> , and their induction has been associated with <protein>growth factor</protein> -stimulated cell proliferation .


We have investigated the induction of these genes by macrophage-CSF ( M-CSF ) in human monocytes that do not proliferate in response to M-CSF but require the factor for optimal cell differentiation .

We have investigated the induction of these genes by <protein>macrophage-CSF</protein> ( <protein>M-CSF</protein> ) in <cell_type>human monocytes</cell_type> that do not proliferate in response to <protein>M-CSF</protein> but require the factor for optimal cell differentiation .


Normal human monocytes were isolated , carefully washed , and incubated for 36 to 48 h in fetal bovine serum-containing medium .

Normal <cell_type>human monocytes</cell_type> were isolated , carefully washed , and incubated for 36 to 48 h in fetal bovine serum-containing medium .


At the end of this incubation the resting cells were stimulated with M-CSF , and RNA was isolated for analysis by Northern blotting .

At the end of this incubation the <cell_type>resting cells</cell_type> were stimulated with <protein>M-CSF</protein> , and RNA was isolated for analysis by Northern blotting .


RNA from control resting cells contained low to undetectable levels of c-jun , fibronectin receptor , and actin mRNA .

RNA from control <cell_type>resting cells</cell_type> contained low to undetectable levels of <rna>c-jun</rna> , <rna>fibronectin receptor</rna> , and <rna>actin mRNA</rna> .


Within 15 to 30 min of addition of M-CSF , however , there was a dramatic coordinate induction of these genes .

Within 15 to 30 min of addition of <protein>M-CSF</protein> , however , there was a dramatic coordinate induction of these genes .


The c-jun gene expression was very transient and was not detectable by 60 min after M-CSF addition .

The <dna>c-jun gene</dna> expression was very transient and was not detectable by 60 min after <protein>M-CSF</protein> addition .


In contrast , the expression of actin and fibronectin receptor mRNA was more sustained , and the expression of these genes remained elevated at 24 to 48 h after M-CSF addition .

In contrast , the expression of <rna>actin and fibronectin receptor mRNA</rna> was more sustained , and the expression of these genes remained elevated at 24 to 48 h after <protein>M-CSF</protein> addition .


We also observed the induction of the myelomonocytic specific tyrosine kinase hck gene simultaneously with the other immediate early response genes .

We also observed the induction of the <dna>myelomonocytic specific tyrosine kinase hck gene</dna> simultaneously with the other <dna>immediate early response genes</dna> .


The protein synthesis inhibitor cycloheximide did not block the induction of any of these genes , and in fact , super-induced the expression of c-jun and hck .

The protein synthesis inhibitor cycloheximide did not block the induction of any of these genes , and in fact , super-induced the expression of <dna>c-jun</dna> and <dna>hck</dna> .


Nuclear run on transcription of the c-jun , hck , and actin genes .

Nuclear run on transcription of the <dna>c-jun</dna> , <dna>hck</dna> , and <dna>actin genes</dna> .


Therefore , in normal human monocytes M-CSF induces immediate early response genes without inducing cell proliferation .

Therefore , in <cell_type>normal human monocytes</cell_type> <protein>M-CSF</protein> induces <dna>immediate early response genes</dna> without inducing cell proliferation .


These genes may then play a role in altering the physiologic status of the cells in response to CSF .

These genes may then play a role in altering the physiologic status of the cells in response to <protein>CSF</protein> .


Inducible nuclear factor binding to the kappa B elements of the human immunodeficiency virus enhancer in T cells can be blocked by cyclosporin A in a signal-dependent manner .

Inducible <protein>nuclear factor</protein> binding to the <dna>kappa B elements</dna> of the <dna>human immunodeficiency virus enhancer</dna> in <cell_type>T cells</cell_type> can be blocked by cyclosporin A in a signal-dependent manner .


Cyclosporin A ( CsA ) is thought to exert its immunosuppressive effects by inhibiting the expression of a distinct set of lymphokine genes which are induced upon T-cell activation , among them the gene coding for interleukin-2 .

Cyclosporin A ( CsA ) is thought to exert its immunosuppressive effects by inhibiting the expression of a distinct set of <dna>lymphokine genes</dna> which are induced upon T-cell activation , among them the gene coding for <protein>interleukin-2</protein> .


In addition , the activation of the human immunodeficiency virus ( HIV ) is partially suppressed .


To better understand the molecular mechanisms underlying suppression by CsA , we have investigated the effects of this drug on transcription factors in T cells .

To better understand the molecular mechanisms underlying suppression by CsA , we have investigated the effects of this drug on <protein>transcription factors</protein> in <cell_type>T cells</cell_type> .


Here we report that the formation of two distinct mitogen-inducible DNA-binding complexes , the kappa B complex within the HIV enhancer and the NFAT-1 complex within the interleukin-2 enhancer , is inhibited in the presence of CsA .

Here we report that the formation of two distinct <protein>mitogen-inducible DNA-binding complexes</protein> , the <protein>kappa B complex</protein> within the <dna>HIV enhancer</dna> and the <protein>NFAT-1 complex</protein> within the <dna>interleukin-2 enhancer</dna> , is inhibited in the presence of CsA .


The kappa B-binding activity with the HIV enhancer is inhibited only if it is activated via the mitogen phytohemagglutinin whereas phorbol myristate acetate-mediated activation is completely insensitive to the drug .

The kappa B-binding activity with the <dna>HIV enhancer</dna> is inhibited only if it is activated via the <protein>mitogen</protein> <protein>phytohemagglutinin</protein> whereas phorbol myristate acetate-mediated activation is completely insensitive to the drug .


This suggests a model in which functionally indistinguishable kappa B complexes can be activated via two separate pathways of signal transduction distinguishable by CsA .

This suggests a model in which functionally indistinguishable <protein>kappa B complexes</protein> can be activated via two separate pathways of signal transduction distinguishable by CsA .


Purification of TCF-1 alpha , a T-cell-specific transcription factor that activates the T-cell receptor C alpha gene enhancer in a context-dependent manner .

Purification of <protein>TCF-1 alpha</protein> , a <protein>T-cell-specific transcription factor</protein> that activates the <dna>T-cell receptor C alpha gene enhancer</dna> in a context-dependent manner .


The differentiation of T cells into functionally diverse subpopulations is controlled in part , by transcriptional activation and silencing ; however , little is known in detail about the proteins that influence this developmental process .

The differentiation of <cell_type>T cells</cell_type> into functionally diverse subpopulations is controlled in part , by transcriptional activation and silencing ; however , little is known in detail about the proteins that influence this developmental process .


We have purified a new T-cell-specific factor , TCF-1 alpha , that is implicated in the activation of genes encoding a major component of the human T-cell receptor ( TCR ) .

We have purified a new <protein>T-cell-specific factor</protein> , <protein>TCF-1 alpha</protein> , that is implicated in the activation of genes encoding a major component of the <protein>human T-cell receptor</protein> ( <protein>TCR</protein> ) .


TCF-1 alpha , originally identified and purified through its binding sites on the HIV-1 promoter , was found to bind to the TCR alpha enhancer and to promoters for several genes expressed at significantly earlier stages of T-cell development than the TCR alpha gene ( e.g. , p56lck and CD3 delta ) .

<protein>TCF-1 alpha</protein> , originally identified and purified through its binding sites on the <dna>HIV-1 promoter</dna> , was found to bind to the <dna>TCR alpha enhancer</dna> and to <dna>promoters</dna> for several <dna>genes</dna> expressed at significantly earlier stages of T-cell development than the <dna>TCR alpha gene</dna> ( e.g. , <dna>p56lck</dna> and <dna>CD3 delta</dna> ) .


Sequences related to the TCF-1 alpha binding motif ( 5'-GGCACCCTTTGA-3 ' ) are also found in the human TCR delta ( and possibly TCR beta ) enhancers .

Sequences related to the <dna>TCF-1 alpha binding motif</dna> ( 5'-GGCACCCTTTGA-3 ' ) are also found in the <dna>human TCR delta</dna> ( and possibly <dna>TCR beta</dna> ) <dna>enhancers</dna> .


Southwestern and gel renaturation experiments with the use of purified protein fractions revealed that TCF-1 alpha activity is derived from a family of 57- to 53-kD proteins that are abundantly expressed in mature and immature T-cell lines ( Jurkat , CCRF-CEM ) and not in mature B cells ( JY , Namalwa ) or nonlymphoid ( HeLa ) cell lines .

Southwestern and gel renaturation experiments with the use of purified protein fractions revealed that <protein>TCF-1 alpha</protein> activity is derived from a family of <protein>57- to 53-kD proteins</protein> that are abundantly expressed in <cell_line>mature and immature T-cell lines</cell_line> ( <cell_line>Jurkat</cell_line> , <cell_line>CCRF-CEM</cell_line> ) and not in <cell_line>mature B cells</cell_line> ( <cell_line>JY</cell_line> , <cell_line>Namalwa</cell_line> ) or <cell_line>nonlymphoid ( HeLa ) cell lines</cell_line> .


A small 95-bp fragment of the TCR alpha control region that contains the TCF-1 alpha binding site juxtaposed between a cAMP-response element ( the CRE or T alpha 1 motif ) and the binding site for a distinct lymphoid-specific protein ( TCF-2 alpha ) behaved as a potent T-cell-specific enhancer in vivo .

A small 95-bp fragment of the <dna>TCR alpha control region</dna> that contains the <dna>TCF-1 alpha binding site</dna> juxtaposed between a <dna>cAMP-response element</dna> ( the <dna>CRE</dna> or <dna>T alpha 1 motif</dna> ) and the <dna>binding site</dna> for a distinct <protein>lymphoid-specific protein</protein> ( <protein>TCF-2 alpha</protein> ) behaved as a potent <dna>T-cell-specific enhancer</dna> in vivo .


Tandem copies of this enhancer functioned synergistically in mature ( Jurkat ) T-cell lines as well as resting and activated immature ( CCRF-CEM ) T-cell lines .

Tandem copies of this enhancer functioned synergistically in <cell_line>mature ( Jurkat ) T-cell lines</cell_line> as well as resting and activated <cell_line>immature ( CCRF-CEM ) T-cell lines</cell_line> .


Mutation of the TCF-1 alpha binding site diminished enhancer activity and disrupted the synergism observed in vivo between tandem enhancer repeats .

Mutation of the <dna>TCF-1 alpha binding site</dna> diminished enhancer activity and disrupted the synergism observed in vivo between <dna>tandem enhancer repeats</dna> .


The TCF-1 alpha binding site was also required for TCR alpha enhancer activity in transcriptionally active extracts from Jurkat but not HeLa cells , confirming that TCF-1 alpha is a T-cell-specific transcription factor .

The <dna>TCF-1 alpha binding site</dna> was also required for <protein>TCR</protein> alpha enhancer activity in transcriptionally active extracts from <cell_line>Jurkat</cell_line> but not <cell_line>HeLa cells</cell_line> , confirming that <protein>TCF-1 alpha</protein> is a <protein>T-cell-specific transcription factor</protein> .


Curiously , the TCF-1 alpha binding element was inactive in vivo when removed from its neighboring elements on the TCR alpha enhancer and positioned in one or more copies upstream of a heterologous promoter .

Curiously , the <protein>TCF-1 alpha</protein> binding element was inactive in vivo when removed from its neighboring elements on the <dna>TCR alpha enhancer</dna> and positioned in one or more copies upstream of a <dna>heterologous promoter</dna> .


Thus , the transcriptional activity of TCF-1 alpha appears to depend on the TCF-2 alpha and T alpha 1 ( CREB ) transcription factors and the context of its binding site within the TCR alpha enhancer .

Thus , the transcriptional activity of <protein>TCF-1 alpha</protein> appears to depend on the <protein>TCF-2 alpha</protein> and <protein>T alpha 1</protein> ( <protein>CREB</protein> ) <protein>transcription factors</protein> and the context of its binding site within the <dna>TCR alpha enhancer</dna> .


Tandem AP-1-binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells .

<dna>Tandem AP-1-binding sites</dna> within the <dna>human beta-globin dominant control region</dna> function as an <dna>inducible enhancer</dna> in <cell_type>erythroid cells</cell_type> .


A powerful enhancer has been mapped to an 18-bp DNA segment located 11 kb 5 ' to the human epsilon-globin gene within the dominant control or locus-activating region .

A powerful enhancer has been mapped to an <dna>18-bp DNA segment</dna> located 11 kb 5 ' to the <dna>human epsilon-globin gene</dna> within the <dna>dominant control</dna> or <dna>locus-activating region</dna> .


This enhancer is inducible in K562 human erythroleukemia cells , increasing linked gamma-globin promoter /luciferase gene expression to 170-fold over an enhancerless construct .

This <dna>enhancer</dna> is inducible in <cell_line>K562 human erythroleukemia cells</cell_line> , increasing linked <dna>gamma-globin promoter</dna> <protein>/luciferase</protein> gene expression to 170-fold over an <dna>enhancerless construct</dna> .


The enhancer consists of tandem AP-1-binding sites , phased 10 bp apart , which are both required for full activity .

The <dna>enhancer</dna> consists of <dna>tandem AP-1-binding sites</dna> , phased 10 bp apart , which are both required for full activity .


DNA-protein binding assays with nuclear extracts from induced cells demonstrate a high molecular weight complex on the enhancer .

DNA-protein binding assays with nuclear extracts from induced cells demonstrate a <protein>high molecular weight complex</protein> on the <dna>enhancer</dna> .


The formation of this complex also requires both AP-1 sites and correlates with maximal enhancer activity .

The formation of this complex also requires both <dna>AP-1 sites</dna> and correlates with maximal <dna>enhancer</dna> activity .


Induction of the enhancer may have a role in the increase in globin gene transcription that characterizes erythroid maturation .

Induction of the <dna>enhancer</dna> may have a role in the increase in <dna>globin gene</dna> transcription that characterizes erythroid maturation .


Enhancer activity appears to be mediated by the binding of a complex of proteins from the jun and fos families to tandem AP-1 consensus sequences .

Enhancer activity appears to be mediated by the binding of a complex of proteins from the <dna>jun and fos families</dna> to <dna>tandem AP-1 consensus sequences</dna> .


Identification of a novel factor that interacts with an immunoglobulin heavy-chain promoter and stimulates transcription in conjunction with the lymphoid cell-specific factor OTF2 .

Identification of a <protein>novel factor</protein> that interacts with an <dna>immunoglobulin heavy-chain promoter</dna> and stimulates transcription in conjunction with the <protein>lymphoid cell-specific factor</protein> <protein>OTF2</protein> .


The tissue-specific expression of the MOPC 141 immunoglobulin heavy-chain gene was studied by using in vitro transcription .

The tissue-specific expression of the <dna>MOPC 141 immunoglobulin heavy-chain gene</dna> was studied by using in vitro transcription .


B-cell-specific transcription of this gene was dependent on the octamer element 5'-ATGCAAAG-3 ' , located in the upstream region of this promoter and in the promoters of all other immunoglobulin heavy- and light-chain genes .

B-cell-specific transcription of this gene was dependent on the <dna>octamer element</dna> 5'-ATGCAAAG-3 ' , located in the <dna>upstream region</dna> of this <dna>promoter</dna> and in the <dna>promoters</dna> of all other <dna>immunoglobulin heavy- and light-chain genes</dna> .


The interaction of purified octamer transcription factors 1 and 2 ( OTF1 and OTF2 ) with the MOPC 141 promoter was studied by using electrophoretic mobility shift assays and DNase I footprinting .

The interaction of purified <protein>octamer transcription factors</protein> 1 and 2 ( <protein>OTF1</protein> and <protein>OTF2</protein> ) with the <dna>MOPC 141 promoter</dna> was studied by using electrophoretic mobility shift assays and <protein>DNase I</protein> footprinting .


Purified OTF1 from HeLa cells and OTF1 and OTF2 from B cells bound to identical sequences within the heavy-chain promoter .

Purified <protein>OTF1</protein> from <cell_line>HeLa cells</cell_line> and <protein>OTF1</protein> and <protein>OTF2</protein> from <cell_type>B cells</cell_type> bound to identical sequences within the <dna>heavy-chain promoter</dna> .


The OTF interactions we observed extended over the heptamer element 5'-CTCAGGA-3 ' , and it seems likely that the binding of the purified factors involves cooperation between octamer and heptamer sites in this promoter .

The OTF interactions we observed extended over the <dna>heptamer element</dna> 5'-CTCAGGA-3 ' , and it seems likely that the binding of the <protein>purified factors</protein> involves cooperation between <dna>octamer and heptamer sites</dna> in this <dna>promoter</dna> .


In addition to these elements , we identified a second regulatory element , the N element with the sequence 5'-GGAACCTCCCCC-3' .

In addition to these elements , we identified a second <dna>regulatory element</dna> , the <dna>N element</dna> with the sequence 5'-GGAACCTCCCCC-3' .


The N element could independently mediate low levels of transcription in both B-cell and HeLa-cell extracts , and , in conjunction with the octamer element , it can promote high levels of transcription in B-cell extracts .

The <dna>N element</dna> could independently mediate low levels of transcription in both B-cell and HeLa-cell extracts , and , in conjunction with the <dna>octamer element</dna> , it can promote high levels of transcription in B-cell extracts .


The N element bound a transcription factor , NTF , that is ubiquitous in cell-type distribution , and NTF was distinct from any of the previously described proteins that bind to similar sequences .

The <dna>N element</dna> bound a <protein>transcription factor</protein> , <protein>NTF</protein> , that is ubiquitous in cell-type distribution , and <protein>NTF</protein> was distinct from any of the <protein>previously described proteins</protein> that bind to similar sequences .


Based on these results , we propose that NTF and OTF2 interactions ( both with their cognate DNA elements and possibly at the protein-protein level ) may be critical to B-cell-specific expression and that these interactions provide additional pathways for regulating gene expression .

Based on these results , we propose that <protein>NTF</protein> and <protein>OTF2</protein> interactions ( both with their <dna>cognate DNA elements</dna> and possibly at the protein-protein level ) may be critical to B-cell-specific expression and that these interactions provide additional pathways for regulating gene expression .


NF-kappa B as inducible transcriptional activator of the granulocyte-macrophage colony-stimulating factor gene .

<protein>NF-kappa B</protein> as inducible <protein>transcriptional activator</protein> of the <dna>granulocyte-macrophage colony-stimulating factor gene</dna> .


The expression of the gene encoding the granulocyte-macrophage colony-stimulating factor ( GM-CSF ) is induced upon activation of T cells with phytohemagglutinin and active phorbolester and upon expression of tax1 , a transactivating protein of the human T-cell leukemia virus type I .

The expression of the gene encoding the <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) is induced upon activation of <cell_type>T cells</cell_type> with <protein>phytohemagglutinin</protein> and active phorbolester and upon expression of <protein>tax1</protein> , a <protein>transactivating protein</protein> of the human T-cell leukemia virus type I .


The same agents induce transcription from the interleukin-2 receptor alpha-chain and interleukin-2 genes , depending on promoter elements that bind the inducible transcription factor NF-kappa B ( or an NF-kappa B-like factor ) .

The same agents induce transcription from the <dna>interleukin-2 receptor alpha-chain and interleukin-2 genes</dna> , depending on <dna>promoter elements</dna> that bind the <protein>inducible transcription factor</protein> <protein>NF-kappa B</protein> ( or an <protein>NF-kappa B-like factor</protein> ) .


We therefore tested the possibility that the GM-CSF gene is also regulated by a cognate motif for the NF-kappa B transcription factor .

We therefore tested the possibility that the <dna>GM-CSF gene</dna> is also regulated by a cognate motif for the <protein>NF-kappa B transcription factor</protein> .


A recent functional analysis by Miyatake et al. ( S. Miyatake , M. Seiki , M. Yoshida , and K. Arai , Mol. Cell. Biol. 8 : 5581-5587 , 1988 ) described a short promoter region in the GM-CSF gene that conferred strong inducibility by T-cell-activating signals and tax1 , but no NF-kappa B-binding motifs were identified .

A recent functional analysis by Miyatake et al. ( S. Miyatake , M. Seiki , M. Yoshida , and K. Arai , Mol. Cell. Biol. 8 : 5581-5587 , 1988 ) described a <dna>short promoter region</dna> in the <dna>GM-CSF gene</dna> that conferred strong inducibility by T-cell-activating signals and <protein>tax1</protein> , but no <dna>NF-kappa B-binding motifs</dna> were identified .


Using electrophoretic mobility shift assays , we showed binding of purified human NF-kappa B and of the NF-kappa B activated in Jurkat T cells to an oligonucleotide comprising the GM-CSF promoter element responsible for mediating responsiveness to T-cell-activating signals and tax1 .

Using electrophoretic mobility shift assays , we showed binding of purified <protein>human NF-kappa B</protein> and of the <protein>NF-kappa B</protein> activated in <cell_line>Jurkat T cells</cell_line> to an oligonucleotide comprising the <dna>GM-CSF promoter element</dna> responsible for mediating responsiveness to T-cell-activating signals and <protein>tax1</protein> .


As shown by a methylation interference analysis and oligonucleotide competition experiments , purified NF-kappa B binds at positions -82 to -91 ( GGGAACTACC ) of the GM-CSF promoter sequence with an affinity similar to that with which it binds to the biologically functional kappa B motif in the beta interferon promoter ( GGGAAATTCC ) .

As shown by a methylation interference analysis and oligonucleotide competition experiments , purified <protein>NF-kappa B</protein> binds at <dna>positions -82 to -91</dna> ( GGGAACTACC ) of the <dna>GM-CSF promoter</dna> sequence with an affinity similar to that with which it binds to the <dna>biologically functional kappa B motif</dna> in the <dna>beta interferon promoter</dna> ( GGGAAATTCC ) .


Two kappa B-like motifs at positions -98 to -108 of the GM-CSF promoter were also recognized but with much lower affinities .

Two <dna>kappa B-like motifs</dna> at <dna>positions -98 to -108</dna> of the <dna>GM-CSF promoter</dna> were also recognized but with much lower affinities .


Our data provide strong evidence that the expression of the GM-CSF gene following T-cell activation is controlled by binding of the NF-kappa B transcription factor to a high-affinity binding site in the GM-CSF promoter .

Our data provide strong evidence that the expression of the <dna>GM-CSF gene</dna> following T-cell activation is controlled by binding of the <protein>NF-kappa B transcription factor</protein> to a <dna>high-affinity binding site</dna> in the <dna>GM-CSF promoter</dna> .


Effects of mitogenic agents upon glucocorticoid action in human tonsillar T-lymphocytes .

Effects of mitogenic agents upon glucocorticoid action in <cell_type>human tonsillar T-lymphocytes</cell_type> .


The treatment of human tonsillar T-lymphocytes with 4-phorbol 12-myristate 13-acetate ( PMA ) , resulted in about two fold increase in glucocorticoid receptor ( GR ) number , without any significant change in the receptor affinity .

The treatment of <cell_type>human tonsillar T-lymphocytes</cell_type> with 4-phorbol 12-myristate 13-acetate ( PMA ) , resulted in about two fold increase in <protein>glucocorticoid receptor</protein> ( <protein>GR</protein> ) number , without any significant change in the receptor affinity .


This increase disappeared in the presence of cycloheximide .


Alone , PMA and calcium ionophore A23187 did not affect , but together stimulated , like phytohaemagglutinin ( PHA ) , leucine and , in particular , thymidine incorporation .

Alone , PMA and calcium ionophore A23187 did not affect , but together stimulated , like <protein>phytohaemagglutinin</protein> ( <protein>PHA</protein> ) , leucine and , in particular , thymidine incorporation .


PMA enhanced slightly the stimulatory effect of PHA .

PMA enhanced slightly the stimulatory effect of <protein>PHA</protein> .


Alone , these agents failed to alter the suppressive effect of dexamethasone on thymidine and leucine incorporation ; however , PMA-A23187 and PMA -PHA combinations appeared to antagonize the suppression by dexamethasone .

Alone , these agents failed to alter the suppressive effect of dexamethasone on thymidine and leucine incorporation ; however , PMA-A23187 and PMA <protein>-PHA</protein> combinations appeared to antagonize the suppression by dexamethasone .


To be or not to be a responder in T-cell responses : ubiquitous oligopeptides in all proteins .


Amino acid sequences of all proteins are essays written in the same language .


Accordingly , the same set of words and phrases ( oligopeptides ) appear in totally unrelated proteins .


The reason that only certain individuals of particular major histocompatibility complex ( MHC ) haplotypes can mount T-cell responses against a given antigen of pathogens is found in the fact that T-cell receptors are designed to recognize 18-20 residue-long peptide fragments sandwiched between two alpha-helices of class I or class II MHC molecules .

The reason that only certain individuals of particular <protein>major histocompatibility complex ( MHC ) haplotypes</protein> can mount T-cell responses against a given antigen of pathogens is found in the fact that <protein>T-cell receptors</protein> are designed to recognize 18-20 residue-long peptide fragments sandwiched between two <protein>alpha-helices</protein> of <protein>class I</protein> or class II MHC molecules .


At this range of peptide lengths , most would appear as self , while nonselfness of the remainders are destined to be quite ambiguous , hence creating responders and nonresponders .


Two distinct signal transmission pathways in T lymphocytes are inhibited by complexes formed between an immunophilin and either FK506 or rapamycin .

Two distinct signal transmission pathways in <cell_type>T lymphocytes</cell_type> are inhibited by complexes formed between an <protein>immunophilin</protein> and either FK506 or rapamycin .


Proliferation and immunologic function of T lymphocytes are initiated by signals from the antigen receptor that are inhibited by the immunosuppressant FK506 but not by its structural analog , rapamycin .

Proliferation and immunologic function of <cell_type>T lymphocytes</cell_type> are initiated by signals from the <protein>antigen receptor</protein> that are inhibited by the immunosuppressant FK506 but not by its structural analog , rapamycin .


On the other hand , interleukin 2 ( IL-2 ) -induced signals are blocked by rapamycin but not by FK506 .

On the other hand , <protein>interleukin 2</protein> ( <protein>IL-2</protein> ) -induced signals are blocked by rapamycin but not by FK506 .


Remarkably , these two drugs inhibit each other 's actions , raising the possibility that both act by means of a common immunophilin ( immunosuppressant binding protein ) .

Remarkably , these two drugs inhibit each other 's actions , raising the possibility that both act by means of a common <protein>immunophilin</protein> ( <protein>immunosuppressant binding protein</protein> ) .


We find that the dissociation constant of rapamycin to the FK506 binding protein FKBP ( Kd = 0.2 nM ) is close to the dissociation constant of FK506 to FKBP ( Kd = 0.4 nM ) and to their effective biologic inhibitory concentrations .

We find that the dissociation constant of rapamycin to the <protein>FK506 binding protein</protein> <protein>FKBP</protein> ( Kd = 0.2 nM ) is close to the dissociation constant of FK506 to <protein>FKBP</protein> ( Kd = 0.4 nM ) and to their effective biologic inhibitory concentrations .


However , an excess of rapamycin is needed to revert FK506-mediated inhibition of IL-2 production , apoptosis , and transcriptional activation of NF-AT , a T-cell-specific transcription factor necessary for IL-2 gene activation .

However , an excess of rapamycin is needed to revert FK506-mediated inhibition of <protein>IL-2</protein> production , apoptosis , and transcriptional activation of <protein>NF-AT</protein> , a <protein>T-cell-specific transcription factor</protein> necessary for <dna>IL-2 gene</dna> activation .


Similarly , an excess of FK506 is needed to revert rapamycin-mediated inhibition of IL-2 -induced proliferation .

Similarly , an excess of FK506 is needed to revert rapamycin-mediated inhibition of <protein>IL-2</protein> -induced proliferation .


The drug concentrations required for antagonism may be explained by the relative affinity of the drugs to , and by the abundance of , the immunophilin FKBP .

The drug concentrations required for antagonism may be explained by the relative affinity of the drugs to , and by the abundance of , the <protein>immunophilin</protein> <protein>FKBP</protein> .


FKBP has been shown to catalyze the interconversion of the cis- and trans-rotamers of the peptidyl-prolyl amide bond of peptide substrates ; here we show that rapamycin , like FK506 , is a potent inhibitor of the rotamase activity of FKBP ( Ki = 0.2 nM ) .

<protein>FKBP</protein> has been shown to catalyze the interconversion of the cis- and trans-rotamers of the <protein>peptidyl-prolyl amide bond</protein> of peptide substrates ; here we show that rapamycin , like FK506 , is a potent inhibitor of the rotamase activity of <protein>FKBP</protein> ( Ki = 0.2 nM ) .


Neither FKBP binding nor inhibition of rotamase activity of FKBP alone is sufficient to explain the biologic actions of these drugs .

Neither <protein>FKBP</protein> binding nor inhibition of rotamase activity of <protein>FKBP</protein> alone is sufficient to explain the biologic actions of these drugs .


Rather , these findings suggest that immunophilin bound to FK506 interferes with antigen receptor -induced signals , while rapamycin bound to the immunophilin interferes with IL-2 -induced signals .

Rather , these findings suggest that <protein>immunophilin</protein> bound to FK506 interferes with <protein>antigen receptor</protein> -induced signals , while rapamycin bound to the <protein>immunophilin</protein> interferes with <protein>IL-2</protein> -induced signals .


Adherence-dependent increase in human monocyte PDGF ( B ) mRNA is associated with increases in c-fos , c-jun , and EGR2 mRNA .

Adherence-dependent increase in <rna>human monocyte PDGF ( B ) mRNA</rna> is associated with increases in <rna>c-fos , c-jun , and EGR2 mRNA</rna> .


Adherence is an important initial step in the transition of a circulating monocyte to a tissue macrophage .

Adherence is an important initial step in the transition of a <cell_type>circulating monocyte</cell_type> to a <cell_type>tissue macrophage</cell_type> .


This differentiation is accompanied by an augmented capacity to generate growth factors .

This differentiation is accompanied by an augmented capacity to generate <protein>growth factors</protein> .


We hypothesized that adherence itself might be an important trigger for a sequence of gene activation culminating in cells with increased mRNA encoding profibrotic growth factors such as platelet-derived growth factor B subunit ( PDGF [ B ] ) and transforming growth factor-beta ( TGF-beta ) .

We hypothesized that adherence itself might be an important trigger for a sequence of gene activation culminating in cells with increased <rna>mRNA</rna> encoding profibrotic <protein>growth factors</protein> such as <protein>platelet-derived growth factor B subunit</protein> ( <protein>PDGF [ B ]</protein> ) and <protein>transforming growth factor-beta</protein> ( <protein>TGF-beta</protein> ) .


After in vitro adherence , human monocytes had a biphasic increase in PDGF ( B ) mRNA with peaks at 6 h and 13 d .

After in vitro adherence , human monocytes had a biphasic increase in <rna>PDGF ( B ) mRNA</rna> with peaks at 6 h and 13 d .


No increase in TGF-beta mRNA was observed .

No increase in <rna>TGF-beta mRNA</rna> was observed .


The 6-h increase in PDGF ( B ) mRNA was adherence dependent , and in addition , was abrogated when the cytoskeletal integrity was compromised by cytochalasin D .

The 6-h increase in <rna>PDGF ( B ) mRNA</rna> was adherence dependent , and in addition , was abrogated when the cytoskeletal integrity was compromised by cytochalasin D .


The 6-h increase in PDGF ( B ) mRNA was unaltered by adherence in the presence of the monocyte stimulus lipopolysaccharide .

The 6-h increase in <rna>PDGF ( B ) mRNA</rna> was unaltered by adherence in the presence of the monocyte stimulus lipopolysaccharide .


Adherence to either fibronectin or collagen-coated plastic had little consistent effect on PDGF ( B ) mRNA accumulation .

Adherence to either fibronectin or collagen-coated plastic had little consistent effect on <rna>PDGF ( B ) mRNA</rna> accumulation .


The increased PDGF ( B ) mRNA observed in adherent monocytes was accompanied by increases in mRNAs of the early growth response genes c-fos ( maximal at 20 min ) , c-jun , and EGR2 ( maximal at 6-24 h ) .

The increased <rna>PDGF ( B ) mRNA</rna> observed in <cell_type>adherent monocytes</cell_type> was accompanied by increases in <rna>mRNAs</rna> of the <dna>early growth response genes</dna> <dna>c-fos</dna> ( maximal at 20 min ) , c-jun , and EGR2 ( maximal at 6-24 h ) .


The increase in c-jun and EGR2 , but not c-fos , mRNA was also abrogated by cytochalasin D .

The increase in c-jun and EGR2 , but not <dna>c-fos</dna> , mRNA was also abrogated by cytochalasin D .


These observations suggest that adherence results in increases of c-fos , c-jun , EGR2 , and PDGF ( B ) mRNA .

These observations suggest that adherence results in increases of <rna>c-fos , c-jun , EGR2 , and PDGF ( B ) mRNA</rna> .


In addition , the increases in c-jun , EGR2 , and PDGF ( B ) may depend on cytoskeletal rearrangement .

In addition , the increases in <dna>c-jun</dna> , <dna>EGR2</dna> , and <protein>PDGF ( B )</protein> may depend on cytoskeletal rearrangement .


Modulation of these events at the time of adherence offers a mechanism by which differential priming of the cells may be accomplished .


Single cell assay of a transcription factor reveals a threshold in transcription activated by signals emanating from the T-cell antigen receptor .

Single cell assay of a <protein>transcription factor</protein> reveals a threshold in transcription activated by signals emanating from the <protein>T-cell antigen receptor</protein> .


Stimulation of T lymphocytes through their antigen receptor leads to the appearance of several transcription factors , including NF-AT and NF-kappa B , which are involved in regulating genes required for immunologic activation .

Stimulation of <cell_type>T lymphocytes</cell_type> through their <protein>antigen receptor</protein> leads to the appearance of several <protein>transcription factors</protein> , including <protein>NF-AT</protein> and <protein>NF-kappa B</protein> , which are involved in regulating genes required for immunologic activation .


To investigate the activity of a single transcription factor in individual viable cells , we have applied an assay that uses the fluorescence-activated cell sorter to quantitate beta-galactosidase ( beta-gal ) .

To investigate the activity of a single <protein>transcription factor</protein> in <cell_type>individual viable cells</cell_type> , we have applied an assay that uses the fluorescence-activated cell sorter to quantitate <protein>beta-galactosidase</protein> ( <protein>beta-gal</protein> ) .


We have analyzed the distribution of NF-AT transcriptional activity among T cells undergoing activation by using a construct in which three tandem copies of the NF-AT-binding site directs transcription of the lacZ gene .

We have analyzed the distribution of <protein>NF-AT</protein> transcriptional activity among <cell_type>T cells</cell_type> undergoing activation by using a construct in which three tandem copies of the <dna>NF-AT-binding site</dna> directs transcription of the <dna>lacZ gene</dna> .


Unexpectedly , stimulation of cloned stably transfected Jurkat T cells leads to a bimodal pattern of beta-gal expression in which some cells express no beta-gal and others express high levels .

Unexpectedly , stimulation of <cell_line>cloned stably transfected Jurkat T cells</cell_line> leads to a bimodal pattern of beta-gal expression in which some cells express no <protein>beta-gal</protein> and others express high levels .


This expression pattern can not be accounted for by cell-cycle position or heritable variation .


Further results , in which beta-gal activity is correlated with NF-AT -binding activity , indicate that the concentration of NF-AT must exceed a critical threshold before transcription initiates .

Further results , in which <protein>beta-gal</protein> activity is correlated with <protein>NF-AT</protein> -binding activity , indicate that the concentration of <protein>NF-AT</protein> must exceed a critical threshold before transcription initiates .


This threshold likely reflects the NF-AT concentration-dependent assembly of transcription complexes at the promoter .

This threshold likely reflects the <protein>NF-AT</protein> concentration-dependent assembly of <protein>transcription complexes</protein> at the <dna>promoter</dna> .


Similar constructs controlled by NF-kappa B or the entire interleukin-2 enhancer show bimodal expression patterns during induction , suggesting that thresholds set by the concentration of transcription factors may be a common property of inducible genes .

Similar constructs controlled by <protein>NF-kappa B</protein> or the entire <dna>interleukin-2 enhancer</dna> show bimodal expression patterns during induction , suggesting that thresholds set by the concentration of <protein>transcription factors</protein> may be a common property of <dna>inducible genes</dna> .


The Epstein-Barr virus ( EBV ) BMRF1 promoter for early antigen ( EA-D ) is regulated by the EBV transactivators , BRLF1 and BZLF1 , in a cell-specific manner .

The <dna>Epstein-Barr virus ( EBV ) BMRF1 promoter</dna> for <protein>early antigen</protein> ( <protein>EA-D</protein> ) is regulated by the <protein>EBV transactivators</protein> , <protein>BRLF1</protein> and <protein>BZLF1</protein> , in a cell-specific manner .


The Epstein-Barr virus early antigen diffuse component ( EA-D ) is essential for Epstein-Barr virus DNA polymerase activity , and its activity is suppressed during latent infection .

The <protein>Epstein-Barr virus early antigen diffuse component</protein> ( <protein>EA-D</protein> ) is essential for Epstein-Barr <dna>virus DNA</dna> polymerase activity , and its activity is suppressed during latent infection .


We investigated the regulation of the promoter ( BMRF1 ) for this early gene by studying its responsiveness in vitro to two immediate-early viral transactivators , BZLF1 ( Z ) and BRLF1 ( R ) , focusing on the differences in response in lymphoid cells and epithelial cells .

We investigated the regulation of the <dna>promoter</dna> ( <dna>BMRF1</dna> ) for this early gene by studying its responsiveness in vitro to two <protein>immediate-early viral transactivators</protein> , <protein>BZLF1</protein> ( <protein>Z</protein> ) and <protein>BRLF1</protein> ( <protein>R</protein> ) , focusing on the differences in response in <cell_type>lymphoid cells</cell_type> and <cell_type>epithelial cells</cell_type> .


In lymphoid cells , Z or R alone produced only small increases in EA-D promoter activity , whereas both transactivators together produced a large stimulatory effect .

In <cell_type>lymphoid cells</cell_type> , <protein>Z</protein> or <protein>R</protein> alone produced only small increases in <dna>EA-D promoter</dna> activity , whereas both <protein>transactivators</protein> together produced a large stimulatory effect .


In epithelial cells , the Z transactivator alone produced maximal stimulation of the EA-D promoter ; the effect of R and Z together was no greater than that of Z alone .

In <cell_type>epithelial cells</cell_type> , the <protein>Z transactivator</protein> alone produced maximal stimulation of the <dna>EA-D promoter</dna> ; the effect of <protein>R</protein> and <protein>Z</protein> together was no greater than that of <protein>Z</protein> alone .


Deletional analysis and site-directed mutagenesis of the EA-D promoter demonstrated that in epithelial cells the potential AP-1 binding site plays an essential role in Z responsiveness , although sequences further upstream are also important .

Deletional analysis and site-directed mutagenesis of the <dna>EA-D promoter</dna> demonstrated that in <cell_type>epithelial cells</cell_type> the potential <dna>AP-1 binding site</dna> plays an essential role in <protein>Z</protein> responsiveness , although sequences further upstream are also important .


In lymphoid cells , only the upstream sequences are required for transactivation by the Z/R combination , and the AP-1 site is dispensable .

In <cell_type>lymphoid cells</cell_type> , only the <dna>upstream sequences</dna> are required for transactivation by the <protein>Z/R</protein> combination , and the <protein>AP-1 site</protein> is dispensable .


These data suggest that EA-D ( BMRF1 ) promoter regulation by Z and R is cell type specific and appears to involve different mechanisms in each cell type .

These data suggest that <dna>EA-D ( BMRF1 ) promoter</dna> regulation by <protein>Z</protein> and <protein>R</protein> is cell type specific and appears to involve different mechanisms in each cell type .


Complementary DNA encoding the human T-cell FK506-binding protein , a peptidylprolyl cis-trans isomerase distinct from cyclophilin .

<dna>Complementary DNA</dna> encoding the <protein>human T-cell FK506-binding protein</protein> , a <protein>peptidylprolyl cis-trans isomerase</protein> distinct from <protein>cyclophilin</protein> .


The recently discovered macrolide FK506 has been demonstrated to have potent immunosuppressive activity at concentrations 100-fold lower than cyclosporin A , a cyclic undecapeptide that is used to prevent rejection after transplantation of bone marrow and organs , such as kidney , heart , and liver .


After the recent discovery that the cyclosporin A-binding protein cyclophilin is identical to peptidylprolyl cis-trans isomerase , a cellular binding protein for FK506 was found to be distinct from cyclophilin but to have the same enzymatic activity .

After the recent discovery that the <protein>cyclosporin A-binding protein</protein> <protein>cyclophilin</protein> is identical to <protein>peptidylprolyl cis-trans isomerase</protein> , a <protein>cellular binding protein</protein> for FK506 was found to be distinct from <protein>cyclophilin</protein> but to have the same enzymatic activity .


In this study , we isolated a cDNA coding for FK506-binding protein ( FKBP ) from human peripheral blood T cells by using mixed 20-mer oligonucleotide probes synthesized on the basis of the sequence , Glu-Asp-Gly-Lys-Lys-Phe-Asp , reported for bovine FKBP .

In this study , we isolated a <dna>cDNA</dna> coding for FK506-binding protein ( <protein>FKBP</protein> ) from human peripheral blood <cell_type>T cells</cell_type> by using mixed 20-mer oligonucleotide probes synthesized on the basis of the sequence , Glu-Asp-Gly-Lys-Lys-Phe-Asp , reported for <protein>bovine FKBP</protein> .


The DNA isolated contained an open reading frame encoding 108 amino acid residues .


The first 40 residues of the deduced amino acid sequence were identical to those of the reported amino-terminal sequence of bovine FKBP , indicating that the DNA sequence isolated represents the gene coding for FKBP .

The first 40 residues of the deduced amino acid sequence were identical to those of the reported amino-terminal sequence of bovine <protein>FKBP</protein> , indicating that the DNA sequence isolated represents the gene coding for <protein>FKBP</protein> .


Computer-assisted analysis of the deduced amino acid sequence indicates that FKBP exhibits no internal homology and does not have significant sequence similarity to any other amino acid sequences of known proteins , including cyclophilin .

Computer-assisted analysis of the deduced amino acid sequence indicates that <protein>FKBP</protein> exhibits no internal homology and does not have significant sequence similarity to any other amino acid sequences of known proteins , including <protein>cyclophilin</protein> .


This result suggests that two catalytically similar proteins , cyclophilin and FKBP , evolved independently .

This result suggests that two catalytically similar proteins , <protein>cyclophilin</protein> and <protein>FKBP</protein> , evolved independently .