The in vitro immunization of peripheral blood lymphocytes from four patients in remission ( S.R. , F.R. , M.M. , P. G. ) with BCR1/25 , a 25-mer pml/ RAR-alpha , did not elicit either a polyclonal or a clonal immune response specific to the peptide .

The in vitro immunization of <cell_type>peripheral blood lymphocytes</cell_type> from four patients in remission ( S.R. , F.R. , M.M. , P. G. ) with BCR1/25 , a 25-mer pml/ <protein>RAR-alpha</protein> , did not elicit either a polyclonal or a clonal immune response specific to the peptide .


We then generated new donor anti-pml/RAR-alpha CD4 ( + ) T-cell clones .

We then generated new donor <cell_line>anti-pml/RAR-alpha CD4 ( + ) T-cell clones</cell_line> .


These clones were tested for their recognition of BCR1/25 .


One clone ( C3/5 , CD3 ( + ) , CD4 ( + ) , CD8 ( - ) ) was selected for further analysis .

One clone ( <cell_line>C3/5 , CD3 ( + ) , CD4 ( + ) , CD8 ( - )</cell_line> ) was selected for further analysis .


Clone C3/5 showed specific proliferation , cytotoxicity , and cytokine ( tumor necrosis factor alpha , granulocyte-macrophage colony-stimulating factor ) production when challenged with autologous lymphoblastic cell lines pulsed with peptide BCR1/25 .

<cell_line>Clone C3/5</cell_line> showed specific proliferation , cytotoxicity , and cytokine ( <protein>tumor necrosis factor alpha</protein> , <protein>granulocyte-macrophage colony-stimulating factor</protein> ) production when challenged with <cell_line>autologous lymphoblastic cell lines</cell_line> pulsed with peptide BCR1/25 .


C3/5 cells developed specific proliferation and cytotoxicity when challenged with peptide-pulsed lymphoblastic cell lines and peripheral blood lymphocytes from the four DR11 ( + ) APL patients .

<cell_line>C3/5 cells</cell_line> developed specific proliferation and cytotoxicity when challenged with <cell_line>peptide-pulsed lymphoblastic cell lines</cell_line> and <cell_type>peripheral blood lymphocytes</cell_type> from the four DR11 ( + ) APL patients .


APL blasts , available only from patients F.R. and P.G. , were not lysed by C3/5 and were unable to present peptide BCR1/25 .

<cell_type>APL blasts</cell_type> , available only from patients F.R. and P.G. , were not lysed by <cell_line>C3/5</cell_line> and were unable to present peptide BCR1/25 .


Incubation of APL cells with IFN-gamma failed to induce HLA class II molecules and recognition by the C3/5 clone .

Incubation of <cell_line>APL cells</cell_line> with <protein>IFN-gamma</protein> failed to induce <protein>HLA class II molecules</protein> and recognition by the <cell_line>C3/5 clone</cell_line> .


Since APL cells do not express HLA class II molecules , we tested in two donors ( D.E. and C.H.R. ) and in patients S.R.and P.G.whether the use of 9-mer peptides ( BCR1/9 ) would generate a CD8 /HLA class I -restricted response .

Since <cell_line>APL cells</cell_line> do not express <protein>HLA class II molecules</protein> , we tested in two donors ( D.E. and C.H.R. ) and in patients S.R.and P.G.whether the use of 9-mer peptides ( BCR1/9 ) would generate a <protein>CD8</protein> <protein>/HLA class I</protein> -restricted response .


No peptide-specific T-cell line or clone could be generated from both donors and patients .

No <cell_line>peptide-specific T-cell line</cell_line> or clone could be generated from both donors and patients .


These findings are discussed in relation to possible therapeutic approaches to the immunotherapy of APL .


The proximal regulatory element of the interferon-gamma promoter mediates selective expression in T cells .

The proximal regulatory element of the <dna>interferon-gamma promoter</dna> mediates selective expression in <cell_type>T cells</cell_type> .


Interferon-gamma ( IFN-gamma ) is produced by natural killer cells and certain subsets of T cells , but the basis for its selective expression is unknown .

<protein>Interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) is produced by <cell_type>natural killer cells</cell_type> and certain subsets of <cell_type>T cells</cell_type> , but the basis for its selective expression is unknown .


Within the region between -108 and -40 base pairs of the IFN-gamma promoter are two conserved and essential regulatory elements , which confer activation-specific expression in T cells .

Within the region between -108 and -40 base pairs of the <protein>IFN-gamma</protein> promoter are two conserved and essential <dna>regulatory elements</dna> , which confer activation-specific expression in <cell_type>T cells</cell_type> .


This report describes studies indicating that the most proximal of these two regulatory elements is an important determinant of its restricted expression .

This report describes studies indicating that the most proximal of these two <dna>regulatory elements</dna> is an important determinant of its restricted expression .


The proximal element is a composite site that binds members of the CREB/ATF , AP-1 , and octamer families of transcription factors .

The proximal element is a composite site that binds members of the <protein>CREB/ATF</protein> , <protein>AP-1</protein> , and <protein>octamer families</protein> of <protein>transcription factors</protein> .


Jun is essential for activation-induced transcription and binds preferably as a heterodimer with ATF-2 .

<protein>Jun</protein> is essential for activation-induced transcription and binds preferably as a heterodimer with <protein>ATF-2</protein> .


In contrast , CREB appears to dampen transcription from this element .

In contrast , <protein>CREB</protein> appears to dampen transcription from this element .


The CpG dinucleotide in this element is selectively methylated in Th2 T cells and other cells that do not express IFN-gamma , and methylation markedly reduces transcription factor binding .

The CpG dinucleotide in this <dna>element</dna> is selectively methylated in <cell_type>Th2 T cells</cell_type> and other cells that do not express <protein>IFN-gamma</protein> , and methylation markedly reduces <protein>transcription factor</protein> binding .


As a target for DNA methylation and for binding of transcription factors that mediate or impede transcription , this element appears to play a central role in controlling IFN-gamma expression .

As a target for DNA methylation and for binding of <protein>transcription factors</protein> that mediate or impede transcription , this element appears to play a central role in controlling <protein>IFN-gamma</protein> expression .


CD40 , but not lipopolysaccharide and anti-IgM stimulation of primary B lymphocytes , leads to a persistent nuclear accumulation of RelB .

<protein>CD40</protein> , but not lipopolysaccharide and <protein>anti-IgM</protein> stimulation of <cell_type>primary B lymphocytes</cell_type> , leads to a persistent nuclear accumulation of <protein>RelB</protein> .


In this study we analyzed the effect of CD40 stimulation on the activity and nuclear appearance of Rel/nuclear factor kappaB ( NF-kappaB ) factors in primary murine B lymphocytes .

In this study we analyzed the effect of <protein>CD40</protein> stimulation on the activity and nuclear appearance of <protein>Rel/nuclear factor kappaB ( NF-kappaB ) factors</protein> in <cell_type>primary murine B lymphocytes</cell_type> .


We show that triggering of CD40 signaling pathway ( s ) by CD40 ligands expressed on L cells led to strong activation of an NF-kappaB-controlled beta-globin reporter gene in primary B lymphocytes from transgenic mice .

We show that triggering of <protein>CD40</protein> signaling pathway ( s ) by <protein>CD40 ligands</protein> expressed on <cell_type>L cells</cell_type> led to strong activation of an <dna>NF-kappaB-controlled beta-globin reporter gene</dna> in <cell_type>primary B lymphocytes</cell_type> from transgenic mice .


Analyses of nuclear translocation of individual members of Rel proteins after CD40 induction of primary B cells showed a strong and long-lasting accumulation of RelB and , less pronounced , of c-Rel .

Analyses of nuclear translocation of individual members of <protein>Rel proteins</protein> after <protein>CD40</protein> induction of <cell_type>primary B cells</cell_type> showed a strong and long-lasting accumulation of <protein>RelB</protein> and , less pronounced , of <protein>c-Rel</protein> .


LPS stimulation did not give rise to a persistent nuclear accumulation of RelB and c-Rel , whereas nuclear c-Rel , but not RelB , accumulated after B cell receptor stimulation .

LPS stimulation did not give rise to a persistent nuclear accumulation of <protein>RelB</protein> and <protein>c-Rel</protein> , whereas nuclear <protein>c-Rel</protein> , but not <protein>RelB</protein> , accumulated after B cell receptor stimulation .


CD40 induced not only nuclear translocation but also de novo synthesis of RelB RNA and protein .

<protein>CD40</protein> induced not only nuclear translocation but also de novo synthesis of <rna>RelB RNA</rna> and protein .


S107 plasmacytoma cells , which express CD40 but are defective for the nuclear appearance of p50/p65-NF-kappaB , do not express RelB after CD40 stimulation .

<cell_line>S107 plasmacytoma cells</cell_line> , which express <protein>CD40</protein> but are defective for the nuclear appearance of <protein>p50/p65-NF-kappaB</protein> , do not express <protein>RelB</protein> after <protein>CD40</protein> stimulation .


In S107 cells stably transfected with relB genes , stimulation of nuclear RelB translocation by CD40 was observed .

In <cell_line>S107 cells</cell_line> stably transfected with <dna>relB genes</dna> , stimulation of nuclear <protein>RelB</protein> translocation by <protein>CD40</protein> was observed .


These results indicate that stimulation of CD40 signaling pathways exerts a long-lasting stimulatory effect on both the transcription and nuclear translocation of RelB .

These results indicate that stimulation of <protein>CD40</protein> signaling pathways exerts a long-lasting stimulatory effect on both the transcription and nuclear translocation of <protein>RelB</protein> .


Since LPS and anti-IgM were unable to activate RelB , CD40 appears to trigger a special program of gene expression involved in the proliferation and/or differentiation of B lymphocytes .

Since LPS and <protein>anti-IgM</protein> were unable to activate <protein>RelB</protein> , <protein>CD40</protein> appears to trigger a special program of gene expression involved in the proliferation and/or differentiation of <cell_type>B lymphocytes</cell_type> .


Identification and characterization of a leukocyte-specific component of the nuclear body .


The nuclear body ( NB ) is a cellular organelle that is involved in the pathogenesis of acute promyelocytic leukemia and viral infection .


The NB is also a target of antibodies in the serum of patients with the autoimmune disease primary biliary cirrhosis .

The NB is also a target of <protein>antibodies</protein> in the serum of patients with the autoimmune disease primary biliary cirrhosis .


In this study , serum from a patient with primary biliary cirrhosis was used to identify a cDNA encoding a novel component of the NB , a 140-kDa protein designated Sp140 .

In this study , serum from a patient with primary biliary cirrhosis was used to identify a cDNA encoding a novel component of the NB , a <protein>140-kDa protein</protein> designated <protein>Sp140</protein> .


The predicted amino acid sequence of the amino-terminal portion of Sp140 was similar to Sp100 , a previously identified NB protein .

The predicted amino acid sequence of the <protein>amino-terminal portion</protein> of <protein>Sp140</protein> was similar to <protein>Sp100</protein> , a previously identified <protein>NB protein</protein> .


The carboxyl portion of Sp140 contained a zinc-finger domain and a bromodomain , motifs that are present in proteins regulating gene transcription .

The <protein>carboxyl portion</protein> of <protein>Sp140</protein> contained a <protein>zinc-finger domain</protein> and a <protein>bromodomain</protein> , motifs that are present in proteins regulating gene transcription .


High levels of Sp140 mRNA were detected in human spleen and peripheral blood leukocytes , but not other human tissues .

High levels of <rna>Sp140 mRNA</rna> were detected in human spleen and <cell_type>peripheral blood leukocytes</cell_type> , but not other human tissues .


The level of SP140 mRNA in myeloid precursor cell lines HL60 and NB4 markedly increased in response to chemically induced cellular differentiation .

The level of <rna>SP140 mRNA</rna> in <cell_line>myeloid precursor cell lines</cell_line> <cell_line>HL60</cell_line> and <cell_line>NB4</cell_line> markedly increased in response to chemically induced cellular differentiation .


Immunohistochemical techniques were used to demonstrate that SP140 localized to the NB in differentiated HL60 and NB4 cells .

Immunohistochemical techniques were used to demonstrate that <protein>SP140</protein> localized to the NB in differentiated <cell_line>HL60</cell_line> and <cell_line>NB4 cells</cell_line> .


The location of Sp140 in the NB , and expression of this gene in cells involved in host defense , suggest that Sp140 may be involved in the pathogenesis of acute promyelocytic leukemia and viral infection .

The location of <protein>Sp140</protein> in the NB , and expression of this gene in cells involved in host defense , suggest that <protein>Sp140</protein> may be involved in the pathogenesis of acute promyelocytic leukemia and viral infection .


Regulation of cytokine and cytokine receptor expression by glucocorticoids .

Regulation of <protein>cytokine</protein> and <protein>cytokine receptor</protein> expression by glucocorticoids .


Glucocorticoids ( GCS ) profoundly inhibit several aspects of T cell immunity largely through inhibition of cytokine expression at the transcriptional and posttranscriptional levels .

Glucocorticoids ( GCS ) profoundly inhibit several aspects of T cell immunity largely through inhibition of <protein>cytokine</protein> expression at the transcriptional and posttranscriptional levels .


GCS were also reported to act indirectly by inducing transforming growth factor-beta expression , which in turn blocks T cell immunity .

GCS were also reported to act indirectly by inducing transforming <protein>growth factor-beta</protein> expression , which in turn blocks T cell immunity .


In exerting their antiproliferative effects , GCS diffuse into target cells where they bind their cytoplasmic receptor , which in turn translocates to the nucleus where it inhibits transcription of cytokine genes through direct binding to the glucocorticoid response elements ( GRE ) , which are located in the promoter region of cytokine genes or , alternatively , through antagonism of the action of transcription factors required for optimal transcriptional activation .

In exerting their antiproliferative effects , GCS diffuse into <cell_type>target cells</cell_type> where they bind their <protein>cytoplasmic receptor</protein> , which in turn translocates to the nucleus where it inhibits transcription of <dna>cytokine genes</dna> through direct binding to the <dna>glucocorticoid response elements</dna> ( <dna>GRE</dna> ) , which are located in the promoter region of <dna>cytokine genes</dna> or , alternatively , through antagonism of the action of <protein>transcription factors</protein> required for optimal transcriptional activation .


In contrast to their inhibitory effects on cytokine expression , GCS up-regulate cytokine receptor expression that correlates with enhanced cytokine effects on target cells .

In contrast to their inhibitory effects on <protein>cytokine</protein> expression , GCS up-regulate <protein>cytokine receptor</protein> expression that correlates with enhanced <protein>cytokine</protein> effects on <cell_type>target cells</cell_type> .


In this review , we summarize the current state of knowledge of the mechanism of action of GCS , including the phenomenon of steroid-induced rebound , which ensues upon GCS withdrawal .


Isolation and characterization of murine fra-1 : induction mediated by CD40 and surface Ig is protein kinase C dependent .

Isolation and characterization of <dna>murine fra-1</dna> : induction mediated by <protein>CD40</protein> and <protein>surface Ig</protein> is <protein>protein kinase C</protein> dependent .


The murine fra-1 gene , encoding Fos-related Ag 1 , was isolated from a splenic cDNA library and sequenced .

The <dna>murine fra-1 gene</dna> , encoding <protein>Fos-related Ag 1</protein> , was isolated from a <dna>splenic cDNA library</dna> and sequenced .


Murine fra-1 was highly homologous to rat and human fra-1 .

<dna>Murine fra-1</dna> was highly homologous to <dna>rat and human fra-1</dna> .


Oligonucleotide primers based on the murine sequence were used to construct a quantitative reverse transcription-PCR assay for gene expression .

Oligonucleotide primers based on the <dna>murine sequence</dna> were used to construct a quantitative reverse transcription-PCR assay for gene expression .


B lymphocyte stimulation via both CD40 and surface Ig ( sIg ) receptors substantially induced fra-1 expression , and for both receptors , induction was protein kinase C ( PKC ) dependent .

<cell_type>B lymphocyte</cell_type> stimulation via both <protein>CD40</protein> and <protein>surface Ig ( sIg ) receptors</protein> substantially induced <dna>fra-1</dna> expression , and for both receptors , induction was <protein>protein kinase C</protein> ( <protein>PKC</protein> ) dependent .


This contrasts with induction of c-fos by both CD40 and sIg , which is PKC independent and indicates that CD40 is capable of signaling through PKC or a closely related kinase .

This contrasts with induction of <dna>c-fos</dna> by both <protein>CD40</protein> and <protein>sIg</protein> , which is <protein>PKC</protein> independent and indicates that <protein>CD40</protein> is capable of signaling through <protein>PKC</protein> or a closely related <protein>kinase</protein> .


Induction of fra-1 following engagement of CD40 did not require protein synthesis , suggesting that the PKC -dependent linkage between CD40 and fra-1 is direct .

Induction of <dna>fra-1</dna> following engagement of <protein>CD40</protein> did not require protein synthesis , suggesting that the <protein>PKC</protein> -dependent linkage between <protein>CD40</protein> and <dna>fra-1</dna> is direct .


CD40 -mediated fra-1 induction did require tyrosine kinase activity .

<protein>CD40</protein> -mediated <dna>fra-1</dna> induction did require <protein>tyrosine kinase</protein> activity .


These results demonstrate that CD40 , like sIg , may employ PKC in producing select outcomes , that individual B cell receptors may signal downstream events via both PKC-dependent and PKC-independent pathways , and that multiple signal transduction pathways may be used to activate the expression of closely related genes .

These results demonstrate that <protein>CD40</protein> , like <protein>sIg</protein> , may employ <protein>PKC</protein> in producing select outcomes , that individual <protein>B cell receptors</protein> may signal downstream events via both PKC-dependent and PKC-independent pathways , and that multiple signal transduction pathways may be used to activate the expression of closely related <dna>genes</dna> .


Pentoxifylline for the treatment of infection with human immunodeficiency virus .


Cytokine dysregulation in human immunodeficiency virus type 1 ( HIV-1 ) infection has been documented in numerous studies and has been cited as an important component in the pathogenesis of this retroviral infection .


Pharmacological modification of cytokine dysregulation , therefore , has been suggested as a therapeutic modality for HIV-1 infection .

Pharmacological modification of <protein>cytokine</protein> dysregulation , therefore , has been suggested as a therapeutic modality for HIV-1 infection .


Dr. Dezube of Beth Israel Hospital ( Boston ) concisely reviews the state of our knowledge regarding the effects of pentoxifylline on expression of tumor necrosis factor-alpha , a cytokine known to influence HIV-1 replication and to play a possible role in the clinical manifestations of advanced infection with this virus .

Dr. Dezube of Beth Israel Hospital ( Boston ) concisely reviews the state of our knowledge regarding the effects of pentoxifylline on expression of <protein>tumor necrosis factor-alpha</protein> , a <protein>cytokine</protein> known to influence HIV-1 replication and to play a possible role in the clinical manifestations of advanced infection with this virus .


Pentoxifylline , a trisubstituted xanthine derivative , has been used to decrease blood viscosity and is reasonably well tolerated by most recipients of the drug .


Results of preliminary studies , many of which were conducted by Dr. Dezube , suggest that use of this agent in combination with antiretroviral compounds may prove useful in the treatment of patients with HIV-1 infection .


Activation of the granulocyte-macrophage colony-stimulating factor promoter in T cells requires cooperative binding of Elf-1 and AP-1 transcription factors .

Activation of the <dna>granulocyte-macrophage colony-stimulating factor promoter</dna> in <cell_type>T cells</cell_type> requires cooperative binding of <protein>Elf-1</protein> and <protein>AP-1</protein> <protein>transcription factors</protein> .


The granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene has been studied extensively as a model system of transcriptional induction during T-lymphocyte activation .

The <dna>granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene</dna> has been studied extensively as a model system of transcriptional induction during T-lymphocyte activation .


The GM-CSF gene is not expressed in resting peripheral blood T cells but is rapidly induced at the transcriptional level following activation through the cell surface T-cell receptor .

The <dna>GM-CSF gene</dna> is not expressed in <cell_type>resting peripheral blood T cells</cell_type> but is rapidly induced at the transcriptional level following activation through the <protein>cell surface T-cell receptor</protein> .


A highly conserved 19-bp element located immediately 5 ' of the human GM-CSF TATA box ( bp -34 to -52 ) , herein called purine box 1 ( PB1 ) , has been shown to bind a T-cell nuclear protein complex and to be required for transcriptional induction of the GM-CSF gene following T-cell activation .

A highly conserved 19-bp element located immediately 5 ' of the <dna>human GM-CSF TATA box</dna> ( <dna>bp -34 to -52</dna> ) , herein called <dna>purine box 1</dna> ( <dna>PB1</dna> ) , has been shown to bind a <protein>T-cell nuclear protein complex</protein> and to be required for transcriptional induction of the <dna>GM-CSF gene</dna> following T-cell activation .


The PB1 sequence motif is highly conserved in both human and murine GM-CSF genes .

The <dna>PB1</dna> sequence motif is highly conserved in both <dna>human and murine GM-CSF genes</dna> .


In this report , we demonstrate that the PB1 element alone confers inducibility on a heterologous promoter following transfection into human Jurkat T cells .

In this report , we demonstrate that the <dna>PB1 element</dna> alone confers inducibility on a heterologous promoter following transfection into <cell_line>human Jurkat T cells</cell_line> .


In addition , we identify a major PB1 nuclear protein-binding complex that is not present in resting peripheral blood T cells but is rapidly induced following T-cell activation .

In addition , we identify a major <protein>PB1 nuclear protein-binding complex</protein> that is not present in <cell_type>resting peripheral blood T cells</cell_type> but is rapidly induced following T-cell activation .


Sequence analysis revealed that PB1 is composed of adjacent binding sites for Ets and AP-1 transcription factors .

Sequence analysis revealed that <dna>PB1</dna> is composed of <dna>adjacent binding sites</dna> for <protein>Ets</protein> and <protein>AP-1</protein> <protein>transcription factors</protein> .


In vitro mutagenesis experiments demonstrated that both the Ets and AP-1 sites are required for binding of the inducible PB1 nuclear protein complex and for the transcriptional activity of this element and the GM-CSF promoter in activated T cells .

In vitro mutagenesis experiments demonstrated that both the <dna>Ets and AP-1 sites</dna> are required for binding of the inducible <protein>PB1 nuclear protein complex</protein> and for the transcriptional activity of this element and the <dna>GM-CSF promoter</dna> in <cell_type>activated T cells</cell_type> .


( ABSTRACT TRUNCATED AT 250 WORDS )


Steroid-resistant asthma .


Cellular mechanisms contributing to inadequate response to glucocorticoid therapy .


The current study examined whether alterations in glucocorticoid receptor ( GR ) binding contribute to poor response to glucocorticoid therapy in asthma .

The current study examined whether alterations in <protein>glucocorticoid receptor</protein> ( <protein>GR</protein> ) binding contribute to poor response to glucocorticoid therapy in asthma .


29 asthma patients with forced expiratory volume in 1 s ( FEV1 ) < 70 % predicted were studied .


Patients were classified as steroid sensitive ( SS ) if their morning FEV1 increased > 30 % after a 1-wk course of oral prednisone 20 mg twice daily and steroid resistant ( SR ) if they failed to increase > 15 % .


PBMC obtained from these two groups , 17 SR and 12 SS , as well as 12 normal controls were analyzed. SR patients had two distinguishable GR binding abnormalities : 15 of the 17 SR patients demonstrated a significantly reduced GR binding affinity , as compared with SS patients ( P = 0.0001 ) and normal controls ( P = 0.0001 ) .

PBMC obtained from these two groups , 17 SR and 12 SS , as well as 12 normal controls were analyzed. SR patients had two distinguishable <protein>GR</protein> binding abnormalities : 15 of the 17 SR patients demonstrated a significantly reduced <protein>GR</protein> binding affinity , as compared with SS patients ( P = 0.0001 ) and normal controls ( P = 0.0001 ) .


This defect was localized to T cells and reverted to normal after 48 h in culture media .

This defect was localized to <cell_type>T cells</cell_type> and reverted to normal after 48 h in culture media .


However , incubation with a combination of IL-2 and IL-4 sustained this abnormality .

However , incubation with a combination of <protein>IL-2</protein> and <protein>IL-4</protein> sustained this abnormality .


The other two SR patients had an abnormally low GR number with normal binding affinity that was not limited to T cells .

The other two SR patients had an abnormally low <protein>GR</protein> number with normal binding affinity that was not limited to <cell_type>T cells</cell_type> .


Furthermore , GR number failed to normalize after incubation in media alone or IL-2 and IL-4 .

Furthermore , <protein>GR</protein> number failed to normalize after incubation in media alone or <protein>IL-2</protein> and <protein>IL-4</protein> .


Therefore , SR asthma may be due to more than one abnormality , the majority related to a reversible cytokine -induced reduction in GR binding affinity and the second related to an irreversible reduction in GR number .

Therefore , SR asthma may be due to more than one abnormality , the majority related to a reversible <protein>cytokine</protein> -induced reduction in <protein>GR</protein> binding affinity and the second related to an irreversible reduction in <protein>GR</protein> number .


These findings may have important implications for the design of alternative treatment approaches for recalcitrant asthma .


Prevalence of aneuploidy , overexpressed ER , and overexpressed EGFR in random breast aspirates of women at high and low risk for breast cancer .

Prevalence of aneuploidy , overexpressed <protein>ER</protein> , and overexpressed <protein>EGFR</protein> in random breast aspirates of women at high and low risk for breast cancer .


Breast tissue biomarkers which accurately predict breast cancer development within a 10 year period in high risk women are needed but currently not available .


We initiated this study to determine 1 ) the prevalence of one or more breast tissue abnormalities in a group of women at high risk for breast cancer , and 2 ) if the prevalence of biomarker abnormalities is greater in high risk than in low risk women .


Eligible high risk women were those with a first degree relative with breast cancer , prior breast cancer , or precancerous mastopathy .


Low risk women were those without these or other major identifiable risk factors .


Ductal cells were obtained via random fine needle aspirations and cytologically classified .

<cell_type>Ductal cells</cell_type> were obtained via random fine needle aspirations and cytologically classified .


Biomarkers included DNA ploidy , estrogen receptor ( ER ) , and epidermal growth factor receptor ( EGFR ) .

Biomarkers included DNA ploidy , <protein>estrogen receptor</protein> ( <protein>ER</protein> ) , and <protein>epidermal growth factor receptor</protein> ( <protein>EGFR</protein> ) .


The prevalence of DNA aneuploidy was 30 % , overexpression of ER 10 % , and overexpression of EGFR 35 % , in the 206 high risk women whose median 10 year Gail risk ( projected probability ) of developing breast cancer was 4.5 % .

The prevalence of DNA aneuploidy was 30 % , overexpression of <protein>ER</protein> 10 % , and overexpression of <protein>EGFR</protein> 35 % , in the 206 high risk women whose median 10 year Gail risk ( projected probability ) of developing breast cancer was 4.5 % .


The prevalence of aneuploidy and overexpressed EGFR was significantly higher in the high risk women than in the 25 low risk controls ( p < 0.002 ) , whose median 10 year Gail risk was 0.7 % .

The prevalence of aneuploidy and overexpressed <protein>EGFR</protein> was significantly higher in the high risk women than in the 25 low risk controls ( p < 0.002 ) , whose median 10 year Gail risk was 0.7 % .


The difference in the prevalence of ER overexpression between high and low risk groups was not statistically significant ( p = 0.095 ) .

The difference in the prevalence of <protein>ER</protein> overexpression between high and low risk groups was not statistically significant ( p = 0.095 ) .


This may be due to the low prevalence of overexpressed ER and the small number of controls .

This may be due to the low prevalence of overexpressed <protein>ER</protein> and the small number of controls .


A significant difference was noted in the prevalence of one or more abnormal biomarkers between the high risk and low risk women ( p < 0.001 ) .


A large prospective trial is needed to determine if one or more of these biomarkers , is predictive of breast cancer development .


Inhibition of nuclear factor kappa B subunit p65 mRNA accumulation in lipopolysaccharide-stimulated human monocytic cells treated with sodium salicylate .

Inhibition of <rna>nuclear factor kappa B subunit p65 mRNA</rna> accumulation in <cell_line>lipopolysaccharide-stimulated human monocytic cells</cell_line> treated with sodium salicylate .


Lipopolysaccharide is one of the most potent trigger substances for monocytes and macrophages causing secretion of inflammatory mediators such as tumor necrosis factor and interleukin-1 .

Lipopolysaccharide is one of the most potent trigger substances for monocytes and macrophages causing secretion of <protein>inflammatory mediators</protein> such as <protein>tumor necrosis factor</protein> and <protein>interleukin-1</protein> .


The nature of the nuclear factors involved in regulation of these cytokine genes is still unknown .

The nature of the nuclear factors involved in regulation of these <dna>cytokine genes</dna> is still unknown .


Nuclear factor kappa B ( NF-kappa B ; heterodimer of p50 and p65 ) proteins have been suggested to play an important role in gene transcription of inflammatory mediators when monocytes are stimulated with lipopolysaccharide .

<protein>Nuclear factor kappa B ( NF-kappa B ; heterodimer of p50 and p65 ) proteins</protein> have been suggested to play an important role in gene transcription of <protein>inflammatory mediators</protein> when <cell_type>monocytes</cell_type> are stimulated with lipopolysaccharide .


Nonsteroidal anti-inflammatory drugs such as salicylates have been used to treat symptoms of inflammation , and a new mechanism of drug action was suggested recently .


Salicylates have been shown to inhibit lipopolysaccharide-induced gene transcription via inhibition of NF-kappa B activation by preventing the degradation of NF-kappa B inhibitor `` I kappa B `` , blocking the translocation of NF-kappa B into the nuclear compartment .

Salicylates have been shown to inhibit lipopolysaccharide-induced gene transcription via inhibition of <protein>NF-kappa B</protein> activation by preventing the degradation of <protein>NF-kappa B inhibitor</protein> `` <protein>I kappa B</protein> `` , blocking the translocation of <protein>NF-kappa B</protein> into the nuclear compartment .


However , the nature of the subunit involved in this mechanism has not been defined .


To examine the mechanisms by which salicylates affect cytokine gene transcription , the amount of active and inactive NF-kappa B and NF-kappa B mRNA , in Porphyromonas gingivalis lipopolysaccharide-stimulated human monocytic cells was assessed .

To examine the mechanisms by which salicylates affect <protein>cytokine</protein> gene transcription , the amount of active and inactive <protein>NF-kappa B</protein> and <rna>NF-kappa B mRNA</rna> , in Porphyromonas gingivalis <cell_line>lipopolysaccharide-stimulated human monocytic cells</cell_line> was assessed .


High doses of sodium salicylate suppressed NF-kappa B p65 mRNA accumulation , resulting in suppression of total NF-kappa B , p50 on tissue oligonucleotide had no effects on lipopolysaccharide-induced NF-kappa B activation .

High doses of sodium salicylate suppressed <protein>NF-kappa B</protein> <rna>p65 mRNA</rna> accumulation , resulting in suppression of total <protein>NF-kappa B</protein> , <protein>p50</protein> on tissue oligonucleotide had no effects on lipopolysaccharide-induced <protein>NF-kappa B</protein> activation .


The data demonstrate that the p65 subunit of NF-kappa B is inhibited by salicylate treatment and highlight the role of salicylate in the control of gene expression of inflammatory mediators .

The data demonstrate that the <protein>p65</protein> subunit of <protein>NF-kappa B</protein> is inhibited by salicylate treatment and highlight the role of salicylate in the control of gene expression of <protein>inflammatory mediators</protein> .


Glucocorticoid-mediated inhibition of RANTES expression in human T lymphocytes .

Glucocorticoid-mediated inhibition of <protein>RANTES</protein> expression in <cell_type>human T lymphocytes</cell_type> .


The chemokine RANTES has been implicated in the pathogenesis of allergic inflammatory diseases including asthma and rhinitis which are frequently treated with glucocorticoids .

The <protein>chemokine</protein> <protein>RANTES</protein> has been implicated in the pathogenesis of allergic inflammatory diseases including asthma and rhinitis which are frequently treated with glucocorticoids .


We observed that dexamethasone dramatically inhibited RANTES mRNA expression dose dependently in anti-CD3 activated Hut-78 T cells and human PBMCs .

We observed that dexamethasone dramatically inhibited <rna>RANTES mRNA</rna> expression dose dependently in <cell_line>anti-CD3 activated Hut-78 T cells</cell_line> and <cell_type>human PBMCs</cell_type> .


Inhibition of RANTES expression did not appear to be secondary to IL-2 inhibition and required binding to the intracellular glucocorticoid receptor .

Inhibition of <protein>RANTES</protein> expression did not appear to be secondary to <protein>IL-2</protein> inhibition and required binding to the intracellular <protein>glucocorticoid receptor</protein> .


The down-regulation of RANTES expression by glucocorticoids in T cells may directly contribute to the efficacy of these agents in suppressing cellular infiltration and to their anti-inflammatory properties .

The down-regulation of <protein>RANTES</protein> expression by glucocorticoids in <cell_type>T cells</cell_type> may directly contribute to the efficacy of these agents in suppressing cellular infiltration and to their anti-inflammatory properties .


Association of TRAF1 , TRAF2 , and TRAF3 with an Epstein-Barr virus LMP1 domain important for B-lymphocyte transformation : role in NF-kappaB activation .

Association of <protein>TRAF1</protein> , <protein>TRAF2</protein> , and <protein>TRAF3</protein> with an <dna>Epstein-Barr virus LMP1 domain</dna> important for <cell_type>B-lymphocyte</cell_type> transformation : role in <protein>NF-kappaB</protein> activation .


The Epstein-Barr virus ( EBV ) transforming protein LMP1 appears to be a constitutively activated tumor necrosis factor receptor ( TNFR ) on the basis of an intrinsic ability to aggregate in the plasma membrane and an association of its cytoplasmic carboxyl terminus ( CT ) with TNFR-associated factors ( TRAFs ) .

The <protein>Epstein-Barr virus ( EBV ) transforming protein LMP1</protein> appears to be a <protein>constitutively activated tumor necrosis factor receptor</protein> ( <protein>TNFR</protein> ) on the basis of an intrinsic ability to aggregate in the plasma membrane and an association of its <protein>cytoplasmic carboxyl terminus</protein> ( <protein>CT</protein> ) with <protein>TNFR-associated factors</protein> ( <protein>TRAFs</protein> ) .


We now show that in EBV-transformed B lymphocytes most of TRAF1 or TRAF3 and 5 % of TRAF2 are associated with LMP1 and that most of LMP1 is associated with TRAF1 or TRAF3 .

We now show that in <cell_line>EBV-transformed B lymphocytes</cell_line> most of <protein>TRAF1</protein> or <protein>TRAF3</protein> and 5 % of <protein>TRAF2</protein> are associated with <protein>LMP1</protein> and that most of <protein>LMP1</protein> is associated with <protein>TRAF1</protein> or <protein>TRAF3</protein> .


TRAF1 , TRAF2 , and TRAF3 bind to a single site in the LMP1 CT corresponding to amino acids ( aa ) 199 to 214 , within a domain which is important for B-lymphocyte growth transformation ( aa 187 to 231 ) .

<protein>TRAF1</protein> , <protein>TRAF2</protein> , and <protein>TRAF3</protein> bind to a single site in the <protein>LMP1 CT</protein> corresponding to amino acids ( aa ) 199 to 214 , within a domain which is important for B-lymphocyte growth transformation ( aa 187 to 231 ) .


Further deletional and alanine mutagenesis analyses and comparison with TRAF binding sequences in CD40 , in CD30 , and in the LMP1 of other lymphycryptoviruses provide the first evidence that PXQXT/S is a core TRAF binding motif .

Further deletional and alanine mutagenesis analyses and comparison with <dna>TRAF binding sequences</dna> in CD40 , in CD30 , and in the <protein>LMP1</protein> of other lymphycryptoviruses provide the first evidence that <dna>PXQXT/S</dna> is a core <dna>TRAF binding motif</dna> .


The negative effects of point mutations in the LMP1 ( 1-231 ) core TRAF binding motif on TRAF binding and NF-kappaB activation genetically link the TRAFs to LMP1 ( 1-231 ) -mediated NF-kappaB activation .

The negative effects of point mutations in the <dna>LMP1 ( 1-231 ) core TRAF binding motif</dna> on TRAF binding and <protein>NF-kappaB</protein> activation genetically link the <protein>TRAFs</protein> to <protein>LMP1</protein> ( 1-231 ) -mediated <protein>NF-kappaB</protein> activation .


NF-kappaB activation by LMP1 ( 1-231 ) is likely to be mediated by TRAF1 /TRAF2 heteroaggregates since TRAF1 is unique among the TRAFs in coactivating NF-kappaB with LMP1 ( 1-231 ) , a TRAF2 dominant-negative mutant can block LMP1 ( 1-231 ) -mediated NF-kappaB activation as well as TRAF1 coactivation , and 30 % of TRAF2 is associated with TRAF1 in EBV-transformed B cells .

<protein>NF-kappaB</protein> activation by <protein>LMP1</protein> ( 1-231 ) is likely to be mediated by <protein>TRAF1</protein> <protein>/TRAF2</protein> heteroaggregates since <protein>TRAF1</protein> is unique among the <protein>TRAFs</protein> in coactivating <protein>NF-kappaB</protein> with <protein>LMP1</protein> ( 1-231 ) , a <protein>TRAF2</protein> dominant-negative mutant can block <protein>LMP1</protein> ( 1-231 ) -mediated <protein>NF-kappaB</protein> activation as well as <protein>TRAF1</protein> coactivation , and 30 % of <protein>TRAF2</protein> is associated with <protein>TRAF1</protein> in EBV-transformed B cells .


TRAF3 is a negative modulator of LMP1 ( 1-231 ) -mediated NF-kappaB activation .

<protein>TRAF3</protein> is a negative modulator of <protein>LMP1</protein> ( 1-231 ) -mediated <protein>NF-kappaB</protein> activation .


Surprisingly , TRAF1 , -2 , or -3 does not interact with the terminal LMP1 CT aa 333 to 386 which can independently mediate NF-kappaB activation .

Surprisingly , <protein>TRAF1 , -2 , or -3</protein> does not interact with the <protein>terminal LMP1 CT</protein> aa 333 to 386 which can independently mediate <protein>NF-kappaB</protein> activation .


The constitutive association of TRAFs with LMP1 through the aa 187 to 231 domain which is important in NF-kappaB activation and primary B-lymphocyte growth transformation implicates TRAF aggregation in LMP1 signaling .

The constitutive association of <protein>TRAFs</protein> with <protein>LMP1</protein> through the <protein>aa 187 to 231 domain</protein> which is important in <protein>NF-kappaB</protein> activation and primary <cell_type>B-lymphocyte</cell_type> growth transformation implicates <protein>TRAF</protein> aggregation in <protein>LMP1</protein> signaling .


Lack of IL-12 signaling in human allergen-specific Th2 cells .

Lack of <protein>IL-12</protein> signaling in <cell_line>human allergen-specific Th2 cells</cell_line> .


IL-12 is a powerful skewer of CD4+ T cell responses toward the Th1 phenotype by inducing IFN-gamma production in naive Th cells .

<protein>IL-12</protein> is a powerful skewer of <cell_type>CD4+ T cell</cell_type> responses toward the Th1 phenotype by inducing <protein>IFN-gamma</protein> production in <cell_line>naive Th cells</cell_line> .


In the present study we addressed the question of whether IL-12 can reverse established Th2 responses into Th1/Th0 responses by inducing IFN-gamma production in memory Th2 cells .

In the present study we addressed the question of whether <protein>IL-12</protein> can reverse established Th2 responses into Th1/Th0 responses by inducing <protein>IFN-gamma</protein> production in <cell_line>memory Th2 cells</cell_line> .


To this aim , allergen-specific CD4+ T cell clones ( TCC ) were generated from the peripheral blood of three atopic patients , and their cytokine profiles were analyzed .

To this aim , <cell_line>allergen-specific CD4+ T cell clones</cell_line> ( <cell_line>TCC</cell_line> ) were generated from the peripheral blood of three atopic patients , and their <protein>cytokine</protein> profiles were analyzed .


The majority of these TCC exhibited a strongly polarized Th2 cytokine profile , and the production of IFN-gamma could not be induced by exogenous IL-12 .

The majority of these <cell_line>TCC</cell_line> exhibited a strongly polarized Th2 <protein>cytokine</protein> profile , and the production of <protein>IFN-gamma</protein> could not be induced by exogenous <protein>IL-12</protein> .


Only those TCC with low IFN-gamma levels in the absence of IL-12 responded to IL-12 by additional enhancement of IFN-gamma production .

Only those <cell_line>TCC</cell_line> with low <protein>IFN-gamma</protein> levels in the absence of <protein>IL-12</protein> responded to <protein>IL-12</protein> by additional enhancement of <protein>IFN-gamma</protein> production .


The IL-12 nonresponsiveness of the Th2 clones was further evident by the total lack of IL-12 -induced phosphorylation of STAT4 ( signal transducer and activator of transcription-4 ) , a transcription factor that is typically involved in IL-12 signaling .

The <protein>IL-12</protein> nonresponsiveness of the <cell_line>Th2 clones</cell_line> was further evident by the total lack of <protein>IL-12</protein> -induced phosphorylation of <protein>STAT4</protein> ( <protein>signal transducer and activator of transcription-4</protein> ) , a <protein>transcription factor</protein> that is typically involved in <protein>IL-12</protein> signaling .


Consequently , IL-12 also failed to induce the DNA-binding activity of STAT4-containing complexes in the nuclei of these Th2 clones .

Consequently , <protein>IL-12</protein> also failed to induce the DNA-binding activity of <protein>STAT4-containing complexes</protein> in the nuclei of these <cell_line>Th2 clones</cell_line> .


All TCC expressed equal levels of the low-affinity IL-12R beta1 subunit .

All <cell_line>TCC</cell_line> expressed equal levels of the <protein>low-affinity IL-12R beta1 subunit</protein> .


Our results indicate that human allergen-specific Th cells with strongly polarized Th2 cytokine profiles do not respond to IL-12 and , therefore , can not be induced to produce IFN-gamma .

Our results indicate that human allergen-specific Th cells with strongly polarized Th2 <protein>cytokine</protein> profiles do not respond to <protein>IL-12</protein> and , therefore , can not be induced to produce <protein>IFN-gamma</protein> .


The apparent high frequency of IL-12-nonresponsive Th cells within the allergen-specific populations in atopic patients predicts a limited skewing potential of IL-12 in the case of established Th2 responses , but only affecting newly recruited naive Th cells .

The apparent high frequency of <cell_line>IL-12-nonresponsive Th cells</cell_line> within the allergen-specific populations in atopic patients predicts a limited skewing potential of <protein>IL-12</protein> in the case of established Th2 responses , but only affecting newly recruited naive <cell_line>Th cells</cell_line> .


Cloning and expression of the Epstein-Barr virus-encoded dUTPase : patients with acute , reactivated or chronic virus infection develop antibodies against the enzyme .

Cloning and expression of the <protein>Epstein-Barr virus-encoded dUTPase</protein> : patients with acute , reactivated or chronic virus infection develop <protein>antibodies</protein> against the <protein>enzyme</protein> .


The gene encoding the Epstein-Barr virus ( EBV ) -specific dUTPase was amplified from virus DNA by PCR .

The gene encoding the <protein>Epstein-Barr virus ( EBV ) -specific dUTPase</protein> was amplified from <dna>virus DNA</dna> by PCR .


The active enzyme was expressed in Escherichia coli and in insect cells as a non-fusion protein .

The active enzyme was expressed in Escherichia coli and in <cell_type>insect cells</cell_type> as a <protein>non-fusion protein</protein> .


The protein from E. coli specifically converted dUTP to dUMP and did not react with other dNTPs or NTPs .


Preliminary experiments yielded a Km value of about 0.8 microM for dUTP .


MAbs against the dUTPase reacted with a protein of approximately 31 kDa in 12-O-tetradecanoyl-phorbol-13-acetate ( TPA ) -stimulated B cells harbouring either type 1 or type 2 EBV .

MAbs against the <protein>dUTPase</protein> reacted with a protein of approximately 31 kDa in <cell_line>12-O-tetradecanoyl-phorbol-13-acetate ( TPA ) -stimulated B cells</cell_line> harbouring either type 1 or type 2 EBV .


The protein was found in untreated cells at low levels , whereas induction of the lytic replication cycle by TPA treatment or by providing the immediate early transactivator BZLF1 in trans resulted in increased expression .

The protein was found in <cell_type>untreated cells</cell_type> at low levels , whereas induction of the lytic replication cycle by TPA treatment or by providing the <protein>immediate early transactivator</protein> <protein>BZLF1</protein> in trans resulted in increased expression .


We demonstrated that the virus dUTPase isolated from EBV-infected cells is a phosphoprotein .

We demonstrated that the <protein>virus dUTPase</protein> isolated from <cell_type>EBV-infected cells</cell_type> is a <protein>phosphoprotein</protein> .


The protein expressed in insect cells was used to test for the presence of specific antibodies in sera from normal , healthy carriers and from patients with various diseases .

The protein expressed in <cell_type>insect cells</cell_type> was used to test for the presence of <protein>specific antibodies</protein> in sera from normal , healthy carriers and from patients with various diseases .


While the sera of EBV-negative individuals ( 0/3 ) or healthy carriers ( 0/33 ) did not contain detectable levels of antibodies , patients with mononucleosis ( 5/18 ) , chronic EBV infection ( 2/7 ) , EBV reactivation ( 7/20 ) and human immunodeficiency virus infection ( 5/24 ) showed elevated antibody titres against the enzyme .


This indicated that the dUTPase is expressed during EBV replication and reactivation .


The enzyme might therefore be a potential target for drug therapy under conditions of active DNA replication .


The catalytic domain of pp56 ( lck ) , but not its regulatory domain , is sufficient for inducing IL-2 production .

The <protein>catalytic domain</protein> of <protein>pp56 ( lck )</protein> , but not its <protein>regulatory domain</protein> , is sufficient for inducing <protein>IL-2</protein> production .


The lymphoid src kinase pp56 ( lck ) has been shown to be essential for the induction of different T lymphocyte responses , including CD4 -mediated enhancement of Ag-induced T cell activation , early T cell differentiation , induction of IL-2 production , and cytotoxicity .

The <protein>lymphoid src kinase</protein> <protein>pp56 ( lck )</protein> has been shown to be essential for the induction of different <cell_type>T lymphocyte</cell_type> responses , including <protein>CD4</protein> -mediated enhancement of Ag-induced T cell activation , early T cell differentiation , induction of <protein>IL-2</protein> production , and cytotoxicity .


It is assumed that pp56 ( lck ) acts on these processes by phosphorylating substrates .

It is assumed that <protein>pp56 ( lck )</protein> acts on these processes by phosphorylating substrates .


However , it has been recently reported that the NH2 regulatory domain is sufficient to mediate CD4 accessory function .

However , it has been recently reported that the <protein>NH2</protein> <protein>regulatory domain</protein> is sufficient to mediate <protein>CD4</protein> accessory function .


In this report we address the contribution of the regulatory and catalytic domains of pp56 ( lck ) to another function of this enzyme independent of CD4 : TCR-induced IL-2 production .

In this report we address the contribution of the <protein>regulatory and catalytic domains</protein> of <protein>pp56 ( lck )</protein> to another function of this enzyme independent of <protein>CD4</protein> : TCR-induced <protein>IL-2</protein> production .


Two pp56 ( lck ) mutants lacking either the entire catalytic domain or the entire NH2 regulatory domain were generated , and their abilities to trigger transactivation of the TCR-regulated nuclear factor of activated T cells ( NF-AT ) region of the IL-2 promoter were compared .

Two <protein>pp56 ( lck ) mutants</protein> lacking either the entire <protein>catalytic domain</protein> or the entire <protein>NH2</protein> <protein>regulatory domain</protein> were generated , and their abilities to trigger transactivation of the <dna>TCR-regulated nuclear factor of activated T cells ( NF-AT ) region</dna> of the <dna>IL-2 promoter</dna> were compared .


Only the catalytic , but not the NH2 regulatory , domain of pp56 ( lck ) was able to induce NF-AT region transactivation on its own and to cooperate with other intracellular signals to trigger this response .

Only the catalytic , but not the <protein>NH2</protein> regulatory , domain of <protein>pp56 ( lck )</protein> was able to induce <protein>NF-AT</protein> region transactivation on its own and to cooperate with other intracellular signals to trigger this response .


Moreover , the catalytic domain of pp56 ( lck ) was able to induce IL-2 cytokine production to an extent similar to that of wild-type pp56 ( lck ) .

Moreover , the <protein>catalytic domain</protein> of <protein>pp56 ( lck )</protein> was able to induce <protein>IL-2</protein> <protein>cytokine</protein> production to an extent similar to that of wild-type <protein>pp56 ( lck )</protein> .


We conclude that different domains of the pp56 ( lck ) molecule contribute to regulate distinct biologic functions .

We conclude that different domains of the <protein>pp56 ( lck )</protein> molecule contribute to regulate distinct biologic functions .


In fact , while the NH2 regulatory domain is sufficient to mediate CD4 accessory function , we show here that the catalytic domain of pp56 ( lck ) is sufficient for induction of IL-2 production , mimicking TCR ligation .

In fact , while the <protein>NH2</protein> <protein>regulatory domain</protein> is sufficient to mediate <protein>CD4</protein> accessory function , we show here that the <protein>catalytic domain</protein> of <protein>pp56 ( lck )</protein> is sufficient for induction of <protein>IL-2</protein> production , mimicking <protein>TCR</protein> ligation .


[ The changes in glucocorticoid receptors in peripheral leukocytes in asthmatic subjects ]

[ The changes in glucocorticoid receptors in <cell_type>peripheral leukocytes</cell_type> in asthmatic subjects ]


The number of glucocorticoid receptors ( GCR ) in peripheral leukocytes was determined by radioligand-binding assay in extrinsic and intrinsic asthmatics .

The number of <protein>glucocorticoid receptors</protein> ( <protein>GCR</protein> ) in <cell_type>peripheral leukocytes</cell_type> was determined by radioligand-binding assay in extrinsic and intrinsic asthmatics .


Their corresponding plasma cortisol levels were assessed .


The results showed that the average number of GCR in asthmatics was significantly lower than that in healthy subjects ( P < 0.01 ) , and there was a linear correlation between the number of GCR and the course of asthma .

The results showed that the average number of <protein>GCR</protein> in asthmatics was significantly lower than that in healthy subjects ( P < 0.01 ) , and there was a linear correlation between the number of <protein>GCR</protein> and the course of asthma .


Besides , there was also a linear correlation between the number of GCR and the age of the initial attack of asthma .

Besides , there was also a linear correlation between the number of <protein>GCR</protein> and the age of the initial attack of asthma .


No difference in plasma cortisol level was found between asthmatics and healthy subjects .


These findings suggest that there is no primary and general impairment of glucocorticoid metabolism in the asthmatics , but the number of GCR in the asthmatics is lower than that in healthy controls .

These findings suggest that there is no primary and general impairment of glucocorticoid metabolism in the asthmatics , but the number of <protein>GCR</protein> in the asthmatics is lower than that in healthy controls .


The decrease of the number of GCR in asthmatics , we think , is related to heredity and repeated attacks of asthma .

The decrease of the number of <protein>GCR</protein> in asthmatics , we think , is related to heredity and repeated attacks of asthma .


Novel aldosterone receptors : specificity-conferring mechanism at the level of the cell membrane .

Novel <protein>aldosterone receptors</protein> : specificity-conferring mechanism at the level of the cell membrane .


Functional studies in extra-renal , nonepithelial cells such as smooth muscle cells and more recently circulating human lymphocytes have provided increasing evidence that aldosterone produces not only classical genomic effects , but also rapid non-genomic effects on transmembrane electrolyte movements .

Functional studies in <cell_type>extra-renal , nonepithelial cells</cell_type> such as <cell_type>smooth muscle cells</cell_type> and more recently circulating <cell_type>human lymphocytes</cell_type> have provided increasing evidence that aldosterone produces not only classical genomic effects , but also rapid non-genomic effects on transmembrane electrolyte movements .


These involve activation of the sodium/proton-exchanger of the cell membrane at very low , physiological concentrations of aldosterone with an acute onset within 1-2 minutes .

These involve activation of the <protein>sodium/proton-exchanger</protein> of the cell membrane at very low , physiological concentrations of aldosterone with an acute onset within 1-2 minutes .


A second messenger cascade involved is the inositol-1 , 4 , 5-trisphosphate/calcium pathway which responds over the same rapid time course .


Such changes clearly can not be explained by genomic mechanisms , which are responsible for later effects than the membrane-related rapid responses .


In addition to its rapid time course the unique characteristics of this new pathway for steroid action include a 10000-fold selectivity for aldosterone over cortisol and the ineffectiveness of spironolactones , classical mineralocorticoid antagonists , as antagonists of the response .


Subsequently binding sites have been demonstrated in the plasma membrane of human lymphocytes which show pharmacological ( aldosterone specificity ) and kinetic ( high turnover ) properties identical with those of the rapid aldosterone effects in the same cells .

Subsequently binding sites have been demonstrated in the plasma membrane of <cell_type>human lymphocytes</cell_type> which show pharmacological ( aldosterone specificity ) and kinetic ( high turnover ) properties identical with those of the rapid aldosterone effects in the same cells .


SDS-PAGE analysis of the receptor protein has shown a molecular weight of approximately 50 kD .

SDS-PAGE analysis of the <protein>receptor protein</protein> has shown a molecular weight of approximately 50 kD .


The present paper reviews the data supporting a new , two-step model for non-genomic and genomic aldosterone effects .


It also suggests a novel specificity-conferring mechanism for mineralocorticoid action at the membrane level .


The macrophage transcription factor PU.1 directs tissue-specific expression of the macrophage colony-stimulating factor receptor .

The <protein>macrophage transcription factor</protein> <protein>PU.1</protein> directs tissue-specific expression of the <protein>macrophage colony-stimulating factor receptor</protein> .


The macrophage colony-stimulating factor ( M-CSF ) receptor is expressed in a tissue-specific fashion from two distinct promoters in monocytes/macrophages and the placenta .

The <protein>macrophage colony-stimulating factor ( M-CSF ) receptor</protein> is expressed in a tissue-specific fashion from two distinct <dna>promoters</dna> in <cell_type>monocytes/macrophages</cell_type> and the placenta .


In order to further understand the transcription factors which play a role in the commitment of multipotential progenitors to the monocyte/macrophage lineage , we have initiated an investigation of the factors which activate the M-CSF receptor very early during the monocyte differentiation process .

In order to further understand the transcription factors which play a role in the commitment of <cell_type>multipotential progenitors</cell_type> to the monocyte/macrophage lineage , we have initiated an investigation of the factors which activate the <protein>M-CSF receptor</protein> very early during the monocyte differentiation process .


Here we demonstrate that the human monocytic M-CSF receptor promoter directs reporter gene activity in a tissue-specific fashion .

Here we demonstrate that the <dna>human monocytic M-CSF receptor promoter</dna> directs reporter gene activity in a tissue-specific fashion .


Since one of the few transcription factors which have been implicated in the regulation of monocyte genes is the macrophage- and B-cell-specific PU.1 transcription factor , we investigated whether PU.1 binds and activates the M-CSF receptor promoter .

Since one of the few <protein>transcription factors</protein> which have been implicated in the regulation of <dna>monocyte genes</dna> is the <protein>macrophage- and B-cell-specific PU.1</protein> <protein>transcription factor</protein> , we investigated whether <protein>PU.1</protein> binds and activates the <dna>M-CSF receptor promoter</dna> .


Here we demonstrate that both in vitro-translated PU.1 and PU.1 from nuclear extracts bind to a specific site in the M-CSF receptor promoter just upstream from the major transcription initiation site .

Here we demonstrate that both in <protein>vitro-translated PU.1</protein> and <protein>PU.1</protein> from nuclear extracts bind to a specific site in the <dna>M-CSF receptor promoter</dna> just upstream from the <dna>major transcription initiation site</dna> .


Mutations in this site which eliminate PU.1 binding decrease M-CSF receptor promoter activity significantly in macrophage cell lines only .

Mutations in this site which eliminate <protein>PU.1</protein> binding decrease <protein>M-CSF receptor</protein> promoter activity significantly in <cell_line>macrophage cell lines</cell_line> only .


Furthermore , PU.1 transactivates the M-CSF receptor promoter in nonmacrophage cells .

Furthermore , <protein>PU.1</protein> transactivates the <dna>M-CSF receptor promoter</dna> in <cell_type>nonmacrophage cells</cell_type> .


These results suggest that PU.1 plays a major role in macrophage gene regulation and development by directing the expression of a receptor for a key macrophage growth factor .

These results suggest that <protein>PU.1</protein> plays a major role in macrophage gene regulation and development by directing the expression of a receptor for a <protein>key macrophage growth factor</protein> .


Increased natural killer cell activity correlates with low or negative expression of the HER-2/neu oncogene in patients with breast cancer .

Increased natural killer cell activity correlates with low or negative expression of the <dna>HER-2/neu oncogene</dna> in patients with breast cancer .


BACKGROUND .


Increased expression of the HER-2/neu oncogene in breast cancer correlates with decreased estrogen receptor concentration and seems to be an important prognostic factor .

Increased expression of the <dna>HER-2/neu oncogene</dna> in breast cancer correlates with decreased <protein>estrogen receptor</protein> concentration and seems to be an important prognostic factor .


The authors investigated whether there is a correlation between HER-2/neu expression and immunologic parameters representing tumor defense in patients with breast cancer .

The authors investigated whether there is a correlation between <protein>HER-2/neu</protein> expression and immunologic parameters representing tumor defense in patients with breast cancer .


METHOD .


A Western blot analysis was used to investigate HER-2/neu expression , whereas a chromium-release assay using the K562 cell line as target was used to measure natural killer ( NK ) cell activity .

A Western blot analysis was used to investigate <protein>HER-2/neu</protein> expression , whereas a chromium-release assay using the <cell_line>K562 cell line</cell_line> as target was used to measure <cell_type>natural killer ( NK ) cell</cell_type> activity .


RESULTS .


In patients with breast cancer , NK cell activity was significantly higher compared with patients with benign tumors ( P = 0.006 ) or healthy control subjects ( P = 0.002 ) .

In patients with breast cancer , <cell_type>NK cell</cell_type> activity was significantly higher compared with patients with <cell_type>benign tumors</cell_type> ( P = 0.006 ) or healthy control subjects ( P = 0.002 ) .


Moreover , 23.3 % of patients with breast cancer showed an overexpression of HER-2/neu protein .

Moreover , 23.3 % of patients with breast cancer showed an overexpression of <protein>HER-2/neu protein</protein> .


Within this group of patients , NK cell activity was significantly lower ( 45.6 +/- 16.1 % ) compared with the group with no HER-2/neu overexpression ( 57.3 +/- 11.0 % ) .

Within this group of patients , <cell_type>NK cell</cell_type> activity was significantly lower ( 45.6 +/- 16.1 % ) compared with the group with no <protein>HER-2/neu</protein> overexpression ( 57.3 +/- 11.0 % ) .


NK cell activity did not increase in patients with HER-2/neu overexpression .

<cell_type>NK cell</cell_type> activity did not increase in patients with <protein>HER-2/neu</protein> overexpression .


Thus , there was a statistically significant correlation of cytolytic effector cell function with HER-2/neu expression of the tumor ( P = 0.003 ) , and HER-2/neu overexpression correlated with a negative estrogen receptor status ( P = 0.005 ) .

Thus , there was a statistically significant correlation of cytolytic effector cell function with <protein>HER-2/neu</protein> expression of the tumor ( P = 0.003 ) , and <protein>HER-2/neu</protein> overexpression correlated with a negative <protein>estrogen receptor</protein> status ( P = 0.005 ) .


CONCLUSION .


These data add further evidence to previous observations from the authors ' laboratory that certain tumor characteristics may be associated with reactions of the host with breast cancer .


[ The value of the clinical test of glucocorticoid receptors of peripheral blood leukocytes in patients with chronic pulmonary heart disease ]

[ The value of the clinical test of <protein>glucocorticoid receptors</protein> of <cell_type>peripheral blood leukocytes</cell_type> in patients with chronic pulmonary heart disease ]


In order to inquire into the functional state of adrenal cortex in patients with pulmonary heart disease , the number of glucocorticoid receptors ( GCR ) of peripheral blood leukocytes in patients with chronic pulmonary heart disease was determined with radioligand-binding assay and the corresponding plasma cortisol levels were assessed with radioimmune assays .

In order to inquire into the functional state of adrenal cortex in patients with pulmonary heart disease , the number of <protein>glucocorticoid receptors</protein> ( <protein>GCR</protein> ) of <cell_type>peripheral blood leukocytes</cell_type> in patients with chronic pulmonary heart disease was determined with radioligand-binding assay and the corresponding plasma cortisol levels were assessed with radioimmune assays .


The results showed that the number of GCR in the patients was significantly reduced ( P < 0.01 ) and it was increased when their health state was improved .

The results showed that the number of <protein>GCR</protein> in the patients was significantly reduced ( P < 0.01 ) and it was increased when their health state was improved .


However , it was still lower than that in healthy subjects ( P < 0.01 ) .


The number of GCR in the patients was greatly increased when these patients were treated with oxygen ( P < 0.01 ) .

The number of <protein>GCR</protein> in the patients was greatly increased when these patients were treated with oxygen ( P < 0.01 ) .


No difference in plasma cortisol was found between the patients and the healthy subjects ( P > 0.05 ) .


These results indicate that the function of adrenal cortex may be improved by the compensation mechanism of the patients , but the lower GCR number was the result of lacking of oxygen in the patients .

These results indicate that the function of adrenal cortex may be improved by the compensation mechanism of the patients , but the lower <protein>GCR</protein> number was the result of lacking of oxygen in the patients .


The number of GCR may be improved by inhalation of oxygen .

The number of <protein>GCR</protein> may be improved by inhalation of oxygen .


Therefore oxygen therapy is helpful in raising the activity of glucocorticoid receptors and controlling the development of the disease .

Therefore oxygen therapy is helpful in raising the activity of <protein>glucocorticoid receptors</protein> and controlling the development of the disease .


Signaling via IL-2 and IL-4 in JAK3-deficient severe combined immunodeficiency lymphocytes : JAK3 -dependent and independent pathways .

Signaling via <protein>IL-2</protein> and <protein>IL-4</protein> in <cell_line>JAK3-deficient severe combined immunodeficiency lymphocytes</cell_line> : <protein>JAK3</protein> -dependent and independent pathways .


Both IL-2 and IL-4 bind to receptors containing the common gamma chain and JAK3 .

Both <protein>IL-2</protein> and <protein>IL-4</protein> bind to receptors containing the <protein>common gamma chain</protein> and <protein>JAK3</protein> .


Although JAK3 is required for proper lymphoid development , the precise roles of this kinase in IL-2 and IL-4 signaling in lymphocytes have not been defined .

Although <protein>JAK3</protein> is required for proper lymphoid development , the precise roles of this kinase in <protein>IL-2</protein> and <protein>IL-4</protein> signaling in <cell_type>lymphocytes</cell_type> have not been defined .


Here , we have studied IL-2 and IL-4 signaling in B cell lines lacking JAK3 .

Here , we have studied <protein>IL-2</protein> and <protein>IL-4</protein> signaling in <cell_line>B cell lines</cell_line> lacking <protein>JAK3</protein> .


Although IL-2 -induced phosphorylation of IL-2R beta , JAK1 , and STAT5 all required the presence of JAK3 , IL-4 -mediated phosphorylation of JAK1 , STAT6 , and insulin receptor substrates 1 and 2 did not .

Although <protein>IL-2</protein> -induced phosphorylation of <protein>IL-2R beta</protein> , <protein>JAK1</protein> , and <protein>STAT5</protein> all required the presence of <protein>JAK3</protein> , <protein>IL-4</protein> -mediated phosphorylation of <protein>JAK1</protein> , <protein>STAT6</protein> , and <protein>insulin receptor</protein> substrates 1 and 2 did not .


However , IL-4 -induced effects were clearly improved following JAK3 expression .

However , <protein>IL-4</protein> -induced effects were clearly improved following <protein>JAK3</protein> expression .


These data indicate that IL-4 signaling occurs in the absence of of JAK3 , but is comparatively inefficient .

These data indicate that <protein>IL-4</protein> signaling occurs in the absence of of <protein>JAK3</protein> , but is comparatively inefficient .


These findings may help in understanding the pathogenesis of the immunodeficiency that occurs with mutations of JAK3 and may suggest a mechanism for the pleiotropic effects of IL-4 .

These findings may help in understanding the pathogenesis of the immunodeficiency that occurs with mutations of <protein>JAK3</protein> and may suggest a mechanism for the pleiotropic effects of <protein>IL-4</protein> .


Elf-1 and Stat5 bind to a critical element in a new enhancer of the human interleukin-2 receptor alpha gene [ published erratum appears in Mol Cell Biol 1997 Apr ; 17 ( 4 ) : 2351 ]

<protein>Elf-1</protein> and <protein>Stat5</protein> bind to a critical element in a new enhancer of the <dna>human interleukin-2 receptor alpha gene</dna> [ published erratum appears in Mol Cell Biol 1997 Apr ; 17 ( 4 ) : 2351 ]


The interleukin 2 receptor alpha-chain ( IL-2R alpha ) gene is a key regulator of lymphocyte proliferation .

The <dna>interleukin 2 receptor alpha-chain ( IL-2R alpha ) gene</dna> is a key regulator of lymphocyte proliferation .


IL-2R alpha is rapidly and potently induced in T cells in response to mitogenic stimuli .

<protein>IL-2R alpha</protein> is rapidly and potently induced in <cell_type>T cells</cell_type> in response to mitogenic stimuli .


Interleukin 2 ( IL-2 ) stimulates IL-2R alpha .

<protein>Interleukin 2</protein> ( <protein>IL-2</protein> ) stimulates <protein>IL-2R alpha</protein> .


transcription , thereby amplifying expression of its own high-affinity receptor .

transcription , thereby amplifying expression of its own <protein>high-affinity receptor</protein> .


IL-2R alpha transcription is at least in part controlled by two positive regulatory regions , PRRI and PRRII .

<protein>IL-2R alpha</protein> transcription is at least in part controlled by two <protein>positive regulatory regions</protein> , <dna>PRRI</dna> and <dna>PRRII</dna> .


PRRI is an inducible proximal enhancer , located between nucleotides -276 and -244 , which contains NF-kappaB and SRE/CArG motifs .

<dna>PRRI</dna> is an <dna>inducible proximal enhancer</dna> , located <dna>between nucleotides -276 and -244</dna> , which contains <dna>NF-kappaB and SRE/CArG motifs</dna> .


PRRII is a T-cell-specific enhancer , located between nucleotides -137 and -64 , which binds the T-cell-specific Ets protein Elf-1 and HMG-I ( Y ) proteins .

<dna>PRRII</dna> is a <dna>T-cell-specific enhancer</dna> , located between nucleotides -137 and -64 , which binds the <protein>T-cell-specific Ets protein</protein> <protein>Elf-1</protein> and <protein>HMG-I ( Y ) proteins</protein> .


However , none of these proximal regions account for the induction of IL-2R alpha transcription by IL-2 .

However , none of these proximal regions account for the induction of IL-2R alpha transcription by <protein>IL-2</protein> .


To find new regulatory regions of the IL-2R alpha gene , 8.5 kb of the 5 ' end noncoding sequence of the IL-2R alpha gene have been sequenced .

To find new <dna>regulatory regions</dna> of the <dna>IL-2R alpha gene</dna> , 8.5 kb of the 5 ' end noncoding sequence of the <dna>IL-2R alpha gene</dna> have been sequenced .


We identified an 86-nucleotide fragment that is 90 % identical to the recently characterized murine IL-2-responsive element ( mIL-2rE ) .

We identified an 86-nucleotide fragment that is 90 % identical to the recently characterized <dna>murine IL-2-responsive element</dna> ( <dna>mIL-2rE</dna> ) .


This putative human IL-2rE , designated PRRIII , confers IL-2 responsiveness on a heterologous promoter .

This putative <dna>human IL-2rE</dna> , designated <dna>PRRIII</dna> , confers <protein>IL-2</protein> responsiveness on a <dna>heterologous promoter</dna> .


PRRIII contains a Stat protein binding site that overlaps with an EBS motif ( GASd/EBSd ) .

<dna>PRRIII</dna> contains a <dna>Stat protein binding site</dna> that overlaps with an <dna>EBS motif</dna> ( <dna>GASd/EBSd</dna> ) .


These are essential for IL-2 inducibility of PRRIII/CAT reporter constructs .

These are essential for <protein>IL-2</protein> inducibility of <dna>PRRIII/CAT reporter constructs</dna> .


IL-2 induced the binding of Stat5a and b proteins to the human GASd element .

<protein>IL-2</protein> induced the binding of <protein>Stat5a and b proteins</protein> to the <dna>human GASd element</dna> .


To confirm the physiological relevance of these findings , we carried out in vivo footprinting experiments which showed that stimulation of IL-2R alpha expression correlated with occupancy of the GASd element .

To confirm the physiological relevance of these findings , we carried out in vivo footprinting experiments which showed that stimulation of <protein>IL-2R alpha</protein> expression correlated with occupancy of the <dna>GASd element</dna> .


Our data demonstrate a major role of the GASd/EBSd element in IL-2R alpha regulation and suggest that the T-cell-specific Elf-1 factor can serve as a transcriptional repressor .

Our data demonstrate a major role of the <dna>GASd/EBSd element</dna> in <protein>IL-2R alpha</protein> regulation and suggest that the <protein>T-cell-specific Elf-1 factor</protein> can serve as a <protein>transcriptional repressor</protein> .


Signal transduction by DR3 , a death domain-containing receptor related to TNFR-1 and CD95 .

Signal transduction by <protein>DR3</protein> , a <protein>death domain-containing receptor</protein> related to <protein>TNFR-1</protein> and <protein>CD95</protein> .


Tumor necrosis factor receptor-1 ( TNFR-1 ) and CD95 ( also called Fas or APO-1 ) are cytokine receptors that engage the apoptosis pathway through a region of intracellular homology , designated the `` death domain . '' Another death domain-containing member of the TNFR family , death receptor 3 ( DR3 ) , was identified and was shown to induce both apoptosis and activation of nuclear factor kappaB .

<protein>Tumor necrosis factor receptor-1</protein> ( <protein>TNFR-1</protein> ) and <protein>CD95</protein> ( also called <protein>Fas</protein> or <protein>APO-1</protein> ) are <protein>cytokine receptors</protein> that engage the apoptosis pathway through a region of intracellular homology , designated the `` <protein>death domain</protein> . '' Another <protein>death domain-containing member</protein> of the <protein>TNFR family</protein> , <protein>death receptor 3</protein> ( <protein>DR3</protein> ) , was identified and was shown to induce both apoptosis and activation of <protein>nuclear factor kappaB</protein> .


Expression of DR3 appears to be restricted to tissues enriched in lymphocytes .

Expression of <protein>DR3</protein> appears to be restricted to tissues enriched in <cell_type>lymphocytes</cell_type> .


DR3 signal transduction is mediated by a complex of intracellular signaling molecules including TRADD , TRAF2 , FADD , and FLICE .

<protein>DR3</protein> signal transduction is mediated by a complex of <protein>intracellular signaling molecules</protein> including <protein>TRADD</protein> , <protein>TRAF2</protein> , <protein>FADD</protein> , and <protein>FLICE</protein> .


Thus , DR3 likely plays a role in regulating lymphocyte homeostasis .

Thus , <protein>DR3</protein> likely plays a role in regulating lymphocyte homeostasis .


Differential nuclear localization of p50 , p52 , and RelB proteins in human accessory cells of the immune response in situ .

Differential nuclear localization of <protein>p50</protein> , <protein>p52</protein> , and <protein>RelB</protein> proteins in <cell_type>human accessory cells</cell_type> of the immune response in situ .


The Rel/NF-kappa B proteins , p50 , p52 , p65 , c-Rel , and RelB , constitute a family of transcription factors involved in the positive regulation of a variety of genes during the immune response .

The <protein>Rel/NF-kappa B proteins</protein> , <protein>p50</protein> , <protein>p52</protein> , <protein>p65</protein> , <protein>c-Rel</protein> , and <protein>RelB</protein> , constitute a family of <protein>transcription factors</protein> involved in the positive regulation of a variety of genes during the immune response .


Recently , it has been shown that RelB knockout mice have no dendritic cells ( DC ) .

Recently , it has been shown that <protein>RelB</protein> knockout mice have no <cell_type>dendritic cells</cell_type> ( <cell_type>DC</cell_type> ) .


An overexpression of p50 has been described in follicular dendritic cells ( FDC ) .

An overexpression of <protein>p50</protein> has been described in <cell_type>follicular dendritic cells</cell_type> ( <cell_type>FDC</cell_type> ) .


A constitutive NF-kappa B activity has been reported in mature macrophages .

A constitutive <protein>NF-kappa B</protein> activity has been reported in <cell_type>mature macrophages</cell_type> .


This led to the hypothesis that some of the Rel/NF-kappa B proteins were key nuclear factors in functions of accessory cells of the immune response .

This led to the hypothesis that some of the <protein>Rel/NF-kappa B proteins</protein> were key <protein>nuclear factors</protein> in functions of <cell_type>accessory cells</cell_type> of the immune response .


Therefore , we investigated in situ the nuclear localization of Rel/NF-kappa B proteins in accessory cells of the immune system by immunohistochemistry and double labeling by immunofluorescence from five normal human tonsils and five lymph nodes with follicular hyperplasia .

Therefore , we investigated in situ the nuclear localization of <protein>Rel/NF-kappa B proteins</protein> in <cell_type>accessory cells</cell_type> of the immune system by immunohistochemistry and double labeling by immunofluorescence from five normal human tonsils and five lymph nodes with follicular hyperplasia .


Nuclear p65 and c-Rel proteins were found in all cell types including lymphocytes .

Nuclear <protein>p65</protein> and <protein>c-Rel</protein> proteins were found in all cell types including <cell_type>lymphocytes</cell_type> .


In germinal centers GC , p50 , p52 , and RelB were found in the nuclei of FDC only and were not detected in the nuclei of CD68+ cells .

In germinal centers GC , <protein>p50</protein> , <protein>p52</protein> , and <protein>RelB</protein> were found in the nuclei of <cell_type>FDC</cell_type> only and were not detected in the nuclei of <cell_line>CD68+ cells</cell_line> .


In T cell areas , p50 , p52 , and RelB were found in the nuclei of HLA-DR+ cells with an antigen-presenting cell ( APC ) morphology .

In T cell areas , <protein>p50</protein> , <protein>p52</protein> , and <protein>RelB</protein> were found in the nuclei of <cell_line>HLA-DR+ cells</cell_line> with an antigen-presenting cell ( APC ) morphology .


p52 and RelB were detected in the nuclei in both CD1a+ and CD68+ cells from the T cell area , whereas p50 was found only in CD68- and CD1a- cells .

<protein>p52</protein> and <protein>RelB</protein> were detected in the nuclei in both <cell_line>CD1a+</cell_line> and <cell_line>CD68+ cells</cell_line> from the T cell area , whereas <protein>p50</protein> was found only in <cell_line>CD68- and CD1a- cells</cell_line> .


Cells with nuclear p50 were negative for the CD38 , CD20 and CD2 markers .

Cells with nuclear <protein>p50</protein> were negative for the <protein>CD38</protein> , <protein>CD20</protein> and <protein>CD2 markers</protein> .


These results show that , physiologically , high levels of nuclear of p50 , p52 and RelB are restricted to accessory cells of the immune system , which include FDC in GC , and DC and macrophages in the T cell zone , that specialized scavenger macrophages from GC do not have detectable levels of p52 and RelB , whereas macrophages from the T cell area , known to present the antigen to T cells , do have both nuclear p52 and RelB , and that in the T cell zone , p52 and RelB are located in nuclei of both CD1a+ , CD68+ or both , cells APC , whereas p50 is restricted to CD1a- and CD68- APC .

These results show that , physiologically , high levels of nuclear of <protein>p50</protein> , <protein>p52</protein> and <protein>RelB</protein> are restricted to <cell_type>accessory cells</cell_type> of the immune system , which include <cell_type>FDC</cell_type> in GC , and <cell_type>DC</cell_type> and macrophages in the T cell zone , that specialized <cell_type>scavenger macrophages</cell_type> from <cell_type>GC</cell_type> do not have detectable levels of <protein>p52</protein> and <protein>RelB</protein> , whereas <cell_type>macrophages</cell_type> from the T cell area , known to present the antigen to <cell_type>T cells</cell_type> , do have both nuclear <protein>p52</protein> and <protein>RelB</protein> , and that in the T cell zone , <protein>p52</protein> and <protein>RelB</protein> are located in nuclei of both <cell_line>CD1a+</cell_line> , <cell_line>CD68+</cell_line> or both , cells <cell_type>APC</cell_type> , whereas <protein>p50</protein> is restricted to <cell_type>CD1a-</cell_type> and <cell_type>CD68- APC</cell_type> .


The different patterns of p50 , p52 and RelB protein nuclear localization may provide insight into their different roles during the immune response in vivo .

The different patterns of <protein>p50</protein> , <protein>p52</protein> and <protein>RelB</protein> protein nuclear localization may provide insight into their different roles during the immune response in vivo .


Tyrosines 113 , 128 , and 145 of SLP-76 are required for optimal augmentation of NFAT promoter activity .

Tyrosines 113 , 128 , and 145 of <protein>SLP-76</protein> are required for optimal augmentation of <dna>NFAT promoter</dna> activity .


SLP-76 ( SH2 domain leukocyte protein of 76 kDa ) is a recently identified substrate of the TCR-stimulated protein tyrosine kinases that functions in the signal transduction cascade linking the TCR with IL-2 gene expression .

<protein>SLP-76</protein> ( <protein>SH2 domain leukocyte protein</protein> of 76 kDa ) is a recently identified substrate of the <protein>TCR-stimulated protein</protein> <protein>tyrosine kinases</protein> that functions in the signal transduction cascade linking the <protein>TCR</protein> with <protein>IL-2</protein> gene expression .


In this report , we demonstrate that engagement of the TCR results in tyrosine phosphorylation of SLP-76 in its amino-terminal acidic region .

In this report , we demonstrate that engagement of the <protein>TCR</protein> results in tyrosine phosphorylation of <protein>SLP-76</protein> in its <protein>amino-terminal acidic region</protein> .


Two tyrosines ( Y113 and Y128 ) fall within an identical five amino-acid motif and are shown to be phosphorylated upon TCR ligation .

Two tyrosines ( Y113 and Y128 ) fall within an identical five amino-acid motif and are shown to be phosphorylated upon <protein>TCR</protein> ligation .


Although mutation of either Y113 and Y128 has a minimal effect on SLP-76 function , mutation of both residues decreases significantly the ability of SLP-76 to promote T cell activation .

Although mutation of either Y113 and Y128 has a minimal effect on <protein>SLP-76</protein> function , mutation of both residues decreases significantly the ability of <protein>SLP-76</protein> to promote T cell activation .


A third tyrosine within the amino-terminal region ( Y145 ) appears to be the most important for optimal SLP-76 function , as altering it alone to phenylalanine has a potent impact on SLP-76 augmentation of NFAT promoter activity .

A third tyrosine within the <protein>amino-terminal region</protein> ( Y145 ) appears to be the most important for optimal <protein>SLP-76</protein> function , as altering it alone to phenylalanine has a potent impact on <protein>SLP-76</protein> augmentation of <dna>NFAT promoter</dna> activity .


Human interferon regulatory factor 2 gene .

<dna>Human interferon regulatory factor 2 gene</dna> .


Intron-exon organization and functional analysis of 5'-flanking region .

Intron-exon organization and functional analysis of <dna>5'-flanking region</dna> .


Interferon regulatory factor 2 ( IRF-2 ) is a transcriptional regulatory protein that terminates interferon beta expression initiated by interferon regulatory factor 1 .

<protein>Interferon regulatory factor 2</protein> ( <protein>IRF-2</protein> ) is a <protein>transcriptional regulatory protein</protein> that terminates <protein>interferon beta</protein> expression initiated by <protein>interferon regulatory factor 1</protein> .


In this study , we isolated the genomic DNA for human IRF-2 gene , determined the intron-exon structure of the human IRF-2 gene , mapped the major transcription initiation site , identified a number of potential regulatory elements in the 5'-flanking region , and localized the IRF-2 gene on human chromosome 4 .

In this study , we isolated the <dna>genomic DNA</dna> for <dna>human IRF-2 gene</dna> , determined the intron-exon structure of the <dna>human IRF-2 gene</dna> , mapped the <dna>major transcription initiation site</dna> , identified a number of potential regulatory elements in the <dna>5'-flanking region</dna> , and localized the <dna>IRF-2 gene</dna> on <dna>human chromosome 4</dna> .


The IRF-2 promoter region contains a CpG island , with several GC boxes , a putative NF-kappa B-binding site , and a CAAT box , but no TATA box .

The <protein>IRF-2</protein> <dna>promoter region</dna> contains a CpG island , with several <dna>GC boxes</dna> , a putative <dna>NF-kappa B-binding site</dna> , and a <dna>CAAT box</dna> , but no <dna>TATA box</dna> .


When the promoter region was linked with a heterologous reporter gene , we found that the promoter region is inducible by both interferons ( interferon-alpha and -gamma ) and interferon regulatory factor 1 .

When the <dna>promoter region</dna> was linked with a <dna>heterologous reporter gene</dna> , we found that the <dna>promoter region</dna> is inducible by both <protein>interferons</protein> ( <protein>interferon-alpha and -gamma</protein> ) and <protein>interferon regulatory factor 1</protein> .


The region which induced these inductions was identified as being confined to 40 nucleotides 5 ' to the major transcriptional initiation site by testing a series of clones with truncated promoter of IRF-2 .

The region which induced these inductions was identified as being confined to <dna>40 nucleotides 5 '</dna> to the <dna>major transcriptional initiation site</dna> by testing a series of clones with <dna>truncated promoter</dna> of <protein>IRF-2</protein> .


This region contains elements which are shared with the transcriptional enhancers of other genes including interferon regulatory factor 1 , interferon beta , and interferon-inducible genes .

This region contains elements which are shared with the <dna>transcriptional enhancers</dna> of other genes including <protein>interferon regulatory factor 1</protein> , <protein>interferon beta</protein> , and <dna>interferon-inducible genes</dna> .


These data suggest that interferon regulatory factor 1 not only triggers the activation of the interferon signal transduction pathway , but also may play a role in limiting the duration of this response by activating the transcription of IRF-2 .

These data suggest that <protein>interferon regulatory factor 1</protein> not only triggers the activation of the <protein>interferon</protein> signal transduction pathway , but also may play a role in limiting the duration of this response by activating the transcription of <protein>IRF-2</protein> .


Interferon alpha selectively affects expression of the human myeloid cell nuclear differentiation antigen in late stage cells in the monocytic but not the granulocytic lineage .

<protein>Interferon alpha</protein> selectively affects expression of the <protein>human myeloid cell nuclear differentiation antigen</protein> in <cell_type>late stage cells</cell_type> in the <cell_type>monocytic</cell_type> but not the <cell_type>granulocytic lineage</cell_type> .


The human myeloid cell nuclear differentiation antigen ( MNDA ) is expressed constitutively in cells of the myeloid lineage , appearing in myeloblast cells in some cases of acute myeloid leukemia and consistently being detected in promyelocyte stage cells as well as in all later stage cells including peripheral blood monocytes and granulocytes .

The <protein>human myeloid cell nuclear differentiation antigen</protein> ( <protein>MNDA</protein> ) is expressed constitutively in cells of the <cell_type>myeloid lineage</cell_type> , appearing in <cell_type>myeloblast cells</cell_type> in some cases of acute myeloid leukemia and consistently being detected in <cell_type>promyelocyte stage cells</cell_type> as well as in all <cell_type>later stage cells</cell_type> including <cell_type>peripheral blood monocytes</cell_type> and <cell_type>granulocytes</cell_type> .


The human myeloid leukemia cell lines , HL-60 , U937 , and THP-1 , express similar levels of immunochemically detectable MNDA .

The <cell_line>human myeloid leukemia cell lines</cell_line> , <cell_line>HL-60</cell_line> , <cell_line>U937</cell_line> , and <cell_line>THP-1</cell_line> , express similar levels of immunochemically detectable <protein>MNDA</protein> .


Although , the level of MNDA mRNA in primary monocytes is very low it was up-regulated at 6 h following the addition of interferon alpha .

Although , the level of <rna>MNDA mRNA</rna> in <cell_type>primary monocytes</cell_type> is very low it was up-regulated at 6 h following the addition of <protein>interferon alpha</protein> .


The effect of interferon alpha on the MNDA mRNA is also observed in the cell lines HL-60 , U937 , and THP-1 .

The effect of <protein>interferon alpha</protein> on the <rna>MNDA mRNA</rna> is also observed in the <cell_line>cell lines</cell_line> <cell_line>HL-60</cell_line> , <cell_line>U937</cell_line> , and <cell_line>THP-1</cell_line> .


The MNDA mRNA level in primary granulocytes was unaffected by addition of interferon alpha and other agents including interferon gamma , endotoxin , poly ( I ) .poly ( C ) , and FMLP .

The <rna>MNDA mRNA</rna> level in <cell_type>primary granulocytes</cell_type> was unaffected by addition of <protein>interferon alpha</protein> and other agents including <protein>interferon gamma</protein> , <protein>endotoxin</protein> , <protein>poly ( I ) .poly ( C )</protein> , and <protein>FMLP</protein> .


The MNDA mRNA level in the myeloid cell lines was also unaffected by the latter four agents .

The <rna>MNDA mRNA</rna> level in the <cell_line>myeloid cell lines</cell_line> was also unaffected by the latter four agents .


Induction of differentiation in the myeloid cell lines with phorbol ester induces monocyte differentiation which was accompanied by a decrease in MNDA mRNA level .

Induction of differentiation in the <cell_line>myeloid cell lines</cell_line> with phorbol ester induces monocyte differentiation which was accompanied by a decrease in <rna>MNDA mRNA</rna> level .


This reduced level of mRNA could then be elevated with subsequent interferon alpha treatment .

This reduced level of <rna>mRNA</rna> could then be elevated with subsequent <protein>interferon alpha</protein> treatment .


The effects of phorbol ester on MNDA mRNA appeared to be associated with induced differentiation since inhibiting cell proliferation did not alter the level of MNDA mRNA and cell cycle variation in MNDA mRNA levels were not observed .

The effects of phorbol ester on <rna>MNDA mRNA</rna> appeared to be associated with induced differentiation since inhibiting cell proliferation did not alter the level of <rna>MNDA mRNA</rna> and cell cycle variation in <rna>MNDA mRNA</rna> levels were not observed .


The ability of interferon alpha to up-regulate MNDA mRNA in phorbol ester treated myeloid cell lines is consistent with the observations made in primary monocytes .

The ability of <protein>interferon alpha</protein> to up-regulate <rna>MNDA mRNA</rna> in phorbol ester treated <cell_line>myeloid cell lines</cell_line> is consistent with the observations made in <cell_type>primary monocytes</cell_type> .


( ABSTRACT TRUNCATED AT 250 WORDS )


Involvement of transcription factor YB-1 in human T-cell lymphotropic virus type I basal gene expression .

Involvement of <protein>transcription factor</protein> <protein>YB-1</protein> in human T-cell lymphotropic virus type I basal gene expression .


Sequences which control basal human T-cell lymphotropic virus type I ( HTLV-I ) transcription likely play an important role in initiation and maintenance of virus replication .


We previously identified and analyzed a 45-nucleotide sequence ( downstream regulatory element 1 [ DRE 1 ] ) , +195 to +240 , at the boundary of the R/U5 region of the long terminal repeat which is required for HTLV-I basal transcription .

We previously identified and analyzed a <dna>45-nucleotide sequence</dna> ( <dna>downstream regulatory element 1</dna> [ <dna>DRE 1</dna> ] ) , <dna>+195 to +240</dna> , at the boundary of the <dna>R/U5 region</dna> of the <dna>long terminal repeat</dna> which is required for HTLV-I basal transcription .


We identified a protein , p37 , which specifically bound to DRE 1 .

We identified a protein , p37 , which specifically bound to <dna>DRE 1</dna> .


An affinity column fraction , containing p37 , stimulated HTLV-I transcription approximately 12-fold in vitro .

An affinity column fraction , containing <protein>p37</protein> , stimulated HTLV-I transcription approximately 12-fold in vitro .


We now report the identification of a cDNA clone ( 15B-7 ) , from a Jurkat expression library , that binds specifically to the DRE 1 regulatory sequence .

We now report the identification of a <dna>cDNA clone</dna> ( <dna>15B-7</dna> ) , from a <dna>Jurkat expression library</dna> , that binds specifically to the <dna>DRE 1 regulatory sequence</dna> .


Binding of the cDNA fusion protein , similarly to the results obtained with purified Jurkat protein , was decreased by introduction of site-specific mutations in the DRE 1 regulatory sequence .

Binding of the <protein>cDNA fusion protein</protein> , similarly to the results obtained with purified Jurkat protein , was decreased by introduction of site-specific mutations in the <dna>DRE 1 regulatory sequence</dna> .


In vitro transcription and translation of 15B-7 cDNA produced a fusion protein which bound specifically to the HTLV-I +195 to +240 oligonucleotide .

In vitro transcription and translation of <dna>15B-7 cDNA</dna> produced a <protein>fusion protein</protein> which bound specifically to the HTLV-I +195 to +240 oligonucleotide .


The partial cDNA encodes a protein which is homologous to the C-terminal 196 amino acids of the 36-kDa transcription factor , YB-1 .

The <dna>partial cDNA</dna> encodes a protein which is homologous to the <protein>C-terminal 196 amino acids</protein> of the <protein>36-kDa transcription factor</protein> , <protein>YB-1</protein> .


Cotransfection of a YB-1 expression plasmid increases HTLV-I basal transcription approximately 14-fold in Jurkat T lymphocytes .

Cotransfection of a <dna>YB-1 expression plasmid</dna> increases HTLV-I basal transcription approximately 14-fold in <cell_line>Jurkat T lymphocytes</cell_line> .


On the basis of the molecular weight , DNA-binding characteristics , and in vivo transactivation activity , we suggest that the previously identified DRE 1 -binding protein , p37 , is YB-1 .

On the basis of the molecular weight , DNA-binding characteristics , and in vivo transactivation activity , we suggest that the previously identified <dna>DRE 1</dna> -binding protein , <protein>p37</protein> , is <protein>YB-1</protein> .


Changes in triiodothyronine ( T3 ) mononuclear leukocyte receptor kinetics after T3 administration and multiple cold-air exposures .


Repeated cold-air exposures increase human triiodothyronine ( T3 ) plasma clearance rates .


To study the response of the nuclear T3 receptor ( NT3R ) in this condition , binding characteristics were analyzed in human mononuclear leukocytes ( MNL ) .

To study the response of the <protein>nuclear T3 receptor</protein> ( <protein>NT3R</protein> ) in this condition , binding characteristics were analyzed in <cell_type>human mononuclear leukocytes</cell_type> ( <cell_type>MNL</cell_type> ) .


In addition , we supplemented one group of individuals with a daily oral replacement dose of T3 to isolate the influence of serum thyroxine ( T4 ) and thyrotropin ( TSH ) levels on receptor kinetics .