A few monocytes were heterogeneous according to their markers ( OKM I and acid phosphatase ) .

A few <cell_type>monocytes</cell_type> were heterogeneous according to their markers ( <protein>OKM I</protein> and acid phosphatase ) .


In 6 cases only there was a strong infiltration of mononuclear cells positive for acid phosphatase .

In 6 cases only there was a strong infiltration of <cell_type>mononuclear cells</cell_type> positive for <protein>acid phosphatase</protein> .


The number of the natural killer cells was also low .

The number of the <cell_type>natural killer cells</cell_type> was also low .


Only a few mononuclear infiltrating cells had receptors for transferrin .


There was a positive correlation between the inflammatory infiltration and the presence of HLA class-I antigens on tumor cell s .

There was a positive correlation between the inflammatory infiltration and the presence of <protein>HLA class-I antigens</protein> on <cell_type>tumor cell</cell_type> s .


Some of the antisera specific for lymphocyte subsets also stained the breast carcinoma cells .

Some of the antisera specific for <cell_type>lymphocyte subsets</cell_type> also stained the <cell_type>breast carcinoma cells</cell_type> .


The great variations in the subsets of mononuclear cells in breast carcinomas may correspond to various systems of defense against neoplasm .

The great variations in the subsets of <cell_type>mononuclear cells</cell_type> in breast carcinomas may correspond to various systems of defense against neoplasm .


A case of male pseudohermaphroditism with normal androgen receptor binding and 47 , XYY karyotype .

A case of male pseudohermaphroditism with normal <protein>androgen receptor</protein> binding and 47 , XYY karyotype .


A case of male pseudohermaphroditism with 47 , XYY karyotype in blood and cutaneous fibroblasts is described .

A case of male pseudohermaphroditism with 47 , XYY karyotype in blood and <cell_type>cutaneous fibroblasts</cell_type> is described .


The plasma testosterone response to HCG stimulation was slightly below the normal range on two occasions suggesting a deficit of gonadal function .


A study of the receptors for dihydrotestosterone in fibroblasts of genital and nongenital skin showed a normal concentration of receptors in genital skin ; 5-alpha-reductase activity in fibroblasts of the genital skin was low , but the plasma relationship testosterone/dihydrotestosterone under HCG stimulation was normal .

A study of the receptors for dihydrotestosterone in <cell_type>fibroblasts</cell_type> of genital and nongenital skin showed a normal concentration of receptors in genital skin ; <protein>5-alpha-reductase</protein> activity in <cell_type>fibroblasts</cell_type> of the genital skin was low , but the plasma relationship testosterone/dihydrotestosterone under HCG stimulation was normal .


The diagnostic possibility of a complete testicular feminization syndrome with normal receptors for dihydrotestosterone is commented on .


1 , 25-Dihydroxyvitamin D3 inhibits antigen-induced T cell activation .

1 , 25-Dihydroxyvitamin D3 inhibits antigen-induced <cell_type>T cell</cell_type> activation .


The proliferative response of murine spleen and thymus cells to antigen but not to lectin was inhibited by the active metabolite of vitamin D3 , 1 , 25- ( OH ) 2D3 .

The proliferative response of <cell_type>murine spleen and thymus cells</cell_type> to <protein>antigen</protein> but not to <protein>lectin</protein> was inhibited by the active metabolite of vitamin D3 , 1 , 25- ( OH ) 2D3 .


To directly examine the effect of 1 , 25- ( OH ) 2D3 on T cell activation in the absence of other complicating interactions , we utilized a panel of cloned Ia-restricted T cell hybridomas that secrete IL 2 on activation by cloned Ia-bearing stimulator cells ( TA3 ) or when stimulated by mitogen .

To directly examine the effect of 1 , 25- ( OH ) 2D3 on <cell_type>T cell</cell_type> activation in the absence of other complicating interactions , we utilized a panel of cloned <cell_line>Ia-restricted T cell hybridomas</cell_line> that secrete <protein>IL 2</protein> on activation by cloned <cell_type>Ia-bearing stimulator cells</cell_type> ( <cell_type>TA3</cell_type> ) or when stimulated by mitogen .


Physiologic concentrations of 1 , 25- ( OH ) 2D3 ( 0.01 to 0.1 nm ) inhibited the antigen-induced secretion of IL 2 by several of these T cell hybridomas .

Physiologic concentrations of 1 , 25- ( OH ) 2D3 ( 0.01 to 0.1 nm ) inhibited the antigen-induced secretion of IL 2 by several of these <cell_line>T cell hybridomas</cell_line> .


This inhibition was dependent on the concentration of the free hormone and could be overcome by increasing the number of Ia-bearing stimulator cells used .

This inhibition was dependent on the concentration of the free hormone and could be overcome by increasing the number of <cell_line>Ia-bearing stimulator cells</cell_line> used .


Pretreatment of the T hybridoma but not the TA3 stimulator cell with 1 , 25- ( OH ) 2D3 resulted in inhibition of activation .

Pretreatment of the <cell_line>T hybridoma</cell_line> but not the <cell_line>TA3 stimulator cell</cell_line> with 1 , 25- ( OH ) 2D3 resulted in inhibition of activation .


These results are consistent with the finding that specific 1 , 25- ( OH ) 2D3 receptors are present on the T cell hybridomas but are lacking in TA3 cells .

These results are consistent with the finding that specific <protein>1 , 25- ( OH ) 2D3 receptors</protein> are present on the T cell hybridomas but are lacking in <cell_line>TA3 cells</cell_line> .


1 , 25- ( OH ) 2D3 failed , however , to inhibit the activation of the T cell hybridomas by lectin or by an anti-Thy-1 antibody .

1 , 25- ( OH ) 2D3 failed , however , to inhibit the activation of the <cell_line>T cell hybridomas</cell_line> by <protein>lectin</protein> or by an <protein>anti-Thy-1 antibody</protein> .


These findings suggest that 1 , 25- ( OH ) 2D3 may be interfering with early events of antigen-induced T cell activation , perhaps by hindering T cell recognition of the relevant antigen on stimulator cell surfaces .

These findings suggest that 1 , 25- ( OH ) 2D3 may be interfering with early events of antigen-induced <cell_type>T cell</cell_type> activation , perhaps by hindering <cell_type>T cell</cell_type> recognition of the relevant antigen on stimulator cell surfaces .


This system should prove useful in studying the molecular mechanisms by which 1 , 25- ( OH ) 2D3 acts to inhibit T cell activation and subsequent IL 2 production .

This system should prove useful in studying the molecular mechanisms by which 1 , 25- ( OH ) 2D3 acts to inhibit T cell activation and subsequent <protein>IL 2</protein> production .


Glucocorticoid receptors and steroid sensitivity in normal and neoplastic human lymphoid tissues : a review .

<protein>Glucocorticoid receptors</protein> and steroid sensitivity in normal and neoplastic human lymphoid tissues : a review .


The determination of estrogen and progesterone receptors in breast cancer has been shown to be useful in predicting the response to endocrine therapy .

The determination of <protein>estrogen and progesterone receptors</protein> in breast cancer has been shown to be useful in predicting the response to endocrine therapy .


Given their well-known inhibitory effects on lymphoid tissue , glucocorticoids have been used widely in the treatment of leukemia .


Given these facts , over the last 10 years , several investigators have measured the number of glucocorticoid receptors in normal and neoplastic lymphoid tissue to see whether their number correlated with glucocorticoid responsiveness in vitro or in vivo .

Given these facts , over the last 10 years , several investigators have measured the number of <protein>glucocorticoid receptors</protein> in normal and neoplastic lymphoid tissue to see whether their number correlated with glucocorticoid responsiveness in vitro or in vivo .


No clear correlation could be established between the level of glucocorticoid receptor and the in vitro action of steroids in normal and neoplastic lymphoid tissue .

No clear correlation could be established between the level of <protein>glucocorticoid receptor</protein> and the in vitro action of steroids in normal and neoplastic lymphoid tissue .


In contrast , attempts to correlate glucocorticoid receptor levels in acute lymphocytic leukemia to in vivo steroid responsiveness and immunological type using the whole-cell-binding assay for receptor determination and selecting the patients according to age and immunological criteria have been more successful .

In contrast , attempts to correlate <protein>glucocorticoid receptor</protein> levels in acute lymphocytic leukemia to in vivo steroid responsiveness and immunological type using the whole-cell-binding assay for receptor determination and selecting the patients according to age and immunological criteria have been more successful .


[ Glucocorticoid receptors in normal human lymphocytes ]

[ <protein>Glucocorticoid receptors</protein> in <cell_type>normal human lymphocytes</cell_type> ]


Glucocorticoid ( GC ) receptors were studied in intact lymphocytes from 11 donors .

<cell_type>Glucocorticoid ( GC ) receptors</cell_type> were studied in intact <cell_type>lymphocytes</cell_type> from 11 donors .


GC binding parameters were found to be highly reproducible in repeated experiments with lymphocytes .

GC binding parameters were found to be highly reproducible in repeated experiments with <cell_type>lymphocytes</cell_type> .


It was shown that GC receptors in donors ' lymphocytes could be distributed into two different classes similarly to the pattern seen in skin fibroblasts .

It was shown that <protein>GC receptors</protein> in donors ' <cell_type>lymphocytes</cell_type> could be distributed into two different classes similarly to the pattern seen in <cell_type>skin fibroblasts</cell_type> .


Human lymphocytes are an adequate object for studying genetically determined variability of GC receptors and its clinical importance .

<cell_type>Human lymphocytes</cell_type> are an adequate object for studying genetically determined variability of <protein>GC receptors</protein> and its clinical importance .


Specific estrogen binding sites in human lymphoid cells and thymic cells .

Specific <protein>estrogen binding sites</protein> in <cell_type>human lymphoid cells</cell_type> and <cell_type>thymic cells</cell_type> .


The binding of estrogen in preparations of human peripheral blood mononuclear cells , as well as by splenic and thymic cells is demonstrated by three different approaches ( Dextran-coated charcoal method , whole cell assay , and gel filtration on a sepharose 4B column ) .

The binding of estrogen in preparations of <cell_type>human peripheral blood mononuclear cells ,</cell_type> as well as by <cell_type>splenic and thymic cells</cell_type> is demonstrated by three different approaches ( Dextran-coated charcoal method , whole cell assay , and gel filtration on a sepharose 4B column ) .


Scatchard 's analysis of [ 3H ] -moxestrol ( R2858 ) and [ 3H ] -estradiol binding proves the existence of a single class of receptor sites having a dissociation constant of 0.18-2.4 X 10 ( -9 ) M .

Scatchard 's analysis of [ 3H ] -moxestrol ( R2858 ) and [ 3H ] -estradiol binding proves the existence of a single class of <protein>receptor sites</protein> having a dissociation constant of 0.18-2.4 X 10 ( -9 ) M .


Physicochemical properties of the binder , including binding capacity and steroid specificity , are quite similar to those reported for the thymus of small mammalian species or human thymoma .


Administration of fibroblast interferon to patients with advanced breast cancer : possible effects on skin metastasis and on hormone receptors .

Administration of <protein>fibroblast interferon</protein> to patients with advanced breast cancer : possible effects on skin metastasis and on <protein>hormone receptors</protein> .


Eleven patients with metastasized breast cancer received 8 intramuscular injections of 6 x 10 ( 6 ) units of human fibroblast interferon over a period of 40 days .

Eleven patients with metastasized breast cancer received 8 intramuscular injections of 6 x 10 ( 6 ) units of <protein>human fibroblast interferon</protein> over a period of 40 days .


The injections did not cause local irritation or inflammation .


Fever occurred in only 1 of the 11 patients .


Although several types of metastases were monitored , only skin nodules consistently ( 10 out of 11 patients ) exhibited changes that were suggestive of a therapeutic effect of the treatment regimen : either a simple decrease in size of some nodules or central necrosis accompanied by an inflammatory reaction .


NK-activity of peripheral blood leukocytes was significantly increased after administration of the first dose ; the effect of subsequent injections was less clear .

NK-activity of <cell_type>peripheral blood leukocytes</cell_type> was significantly increased after administration of the first dose ; the effect of subsequent injections was less clear .


Receptors for estrogens and progestogens were increased in the tumor biopsies of 2 out of 2 and 5 out of 6 patients tested respectively .


Decreased glucocorticoid receptor binding in adrenal insufficiency .

Decreased <protein>glucocorticoid receptor</protein> binding in adrenal insufficiency .


To examine the effect of glucocorticoid deficiency on the glucocorticoid receptor , we examine the binding of [ 3H ] dexamethasone to lymphocytes in normal subjects and patients with adrenal insufficiency before and after glucocorticoid replacement therapy .

To examine the effect of glucocorticoid deficiency on the <protein>glucocorticoid receptor</protein> , we examine the binding of [ 3H ] dexamethasone to <cell_type>lymphocytes</cell_type> in normal subjects and patients with adrenal insufficiency before and after glucocorticoid replacement therapy .


Using a whole cell competitive binding assay , normal human lymphocytes had 5977 +/- 1487 ( mean +/- SD ) binding sites/cell and a dissociation constant of 10 +/- 2 nM .

Using a whole cell competitive binding assay , <cell_type>normal human lymphocytes</cell_type> had 5977 +/- 1487 ( mean +/- SD ) binding sites/cell and a dissociation constant of 10 +/- 2 nM .


Lymphocytes from patients with untreated adrenal insufficiency had fewer binding sites ( 3364 +/-322 ) and a 2-fold increase in binding affinity ( 5.4 +/- 0.9 mM ) .

<cell_type>Lymphocytes</cell_type> from patients with untreated adrenal insufficiency had fewer <protein>binding sites</protein> ( 3364 +/-322 ) and a 2-fold increase in binding affinity ( 5.4 +/- 0.9 mM ) .


The administration of conventional replacement doses of cortisone acetate for 6 months caused no change in receptor number , but was associated with a decrease in binding affinity toward normal .


After long term glucocorticoid replacement therapy , binding parameters were similar to those in patients before treatment .


The physiological implications of the decreased receptor number and increased binding affinity in adrenal insufficiency remain to be elucidated .


Glucocorticoid receptor concentrations and terminal transferase activity as indicators of prognosis in acute non-lymphocytic leukaemia .

<protein>Glucocorticoid receptor</protein> concentrations and terminal <protein>transferase</protein> activity as indicators of prognosis in acute non-lymphocytic leukaemia .


Activity of terminal deoxynucleotidyl transferase ( TdT ) , adenosine deaminase , and 5'nucleotidase and the cellular concentration of glucocorticoid ( dexamethasone ) receptor were determined in 25 patients with acute non-lymphocytic leukaemia .

Activity of <protein>terminal deoxynucleotidyl transferase</protein> ( <protein>TdT</protein> ) , <protein>adenosine deaminase</protein> , and <protein>5'nucleotidase</protein> and the cellular concentration of <protein>glucocorticoid ( dexamethasone ) receptor</protein> were determined in 25 patients with acute non-lymphocytic leukaemia .


All patients were treated according to a common protocol .


Increased activity of TdT ( greater than 0.1 unit/microgram DNA ) was found in 11 patients .

Increased activity of <protein>TdT</protein> ( greater than 0.1 unit/microgram DNA ) was found in 11 patients .


This group of patients was shown to have higher remission and survival rates ( p = 0.06 ) compared with patients with low activity of TdT .


The glucocorticoid receptor concentration of the leukaemic blast cells ranged from 0 to 0.94 fmol/microgram DNA .

The <protein>glucocorticoid receptor</protein> concentration of the <cell_type>leukaemic blast cells</cell_type> ranged from 0 to 0.94 fmol/microgram DNA .


Thirteen patients had blast cells with a glucocorticoid receptor concentration over 0.22 fmol/microgram DNA .

Thirteen patients had <cell_type>blast cells</cell_type> with a <protein>glucocorticoid receptor</protein> concentration over 0.22 fmol/microgram DNA .


These patients had significantly increased remission and survival rates ( p = 0.006 ) compared with those with a low receptor concentration .


This finding can not be explained by a difference in sensitivity to glucocorticoids since these were not used as therapeutic agents .


Adenosine deaminase and 5'nucleotidase activities both varied within two orders of magnitude .

<protein>Adenosine deaminase</protein> and <protein>5'nucleotidase</protein> activities both varied within two orders of magnitude .


No correlation could be found between activities of these enzymes and remission or survival rate .


These results show that measurements of TdT activity and the glucocorticoid receptor concentration yield valuable prognostic information in acute non-lymphocytic leukaemia

These results show that measurements of <protein>TdT</protein> activity and the <protein>glucocorticoid receptor</protein> concentration yield valuable prognostic information in acute non-lymphocytic leukaemia


[ 3H ] cortivazol : a unique high affinity ligand for the glucocorticoid receptor .

[ 3H ] cortivazol : a unique high affinity ligand for the <protein>glucocorticoid receptor</protein> .


Cortivazol ( CVZ ) and deacylcortivazol ( DAC ) are pyrazolosteroids with potent glucocorticoid activity .


In previous work we showed that DAC is 40-fold more potent than dexamethasone ( DEX ) in lysing leukemic lymphoblasts .

In previous work we showed that DAC is 40-fold more potent than dexamethasone ( DEX ) in lysing <cell_type>leukemic lymphoblasts</cell_type> .


To assess the interaction between these atypical steroids and the glucocorticoid receptor , we examined the binding of [ 3H ] CVZ to cytosol from glucocorticoid-sensitive and -resistant variants of the human leukemic cell line CEM C7 .

To assess the interaction between these atypical steroids and the <protein>glucocorticoid receptor</protein> , we examined the binding of [ 3H ] CVZ to cytosol from <cell_line>glucocorticoid-sensitive and -resistant variants</cell_line> of the <cell_line>human leukemic cell line</cell_line> <cell_line>CEM C7</cell_line> .


In glucocorticoid-sensitive cells [ 3H ] CVZ causes a 2-fold induction of glutamine synthetase and binds to a protein in the 4.6 S region of high salt sucrose gradients .

In <cell_line>glucocorticoid-sensitive cells</cell_line> [ 3H ] CVZ causes a 2-fold induction of <protein>glutamine synthetase</protein> and binds to a protein in the 4.6 S region of high salt sucrose gradients .


On DEAE-cellulose chromatography , [ 3H ] CVZ-receptor complexes show a shift from high ( 0.25 M KP ) to low salt ( 0.09 M KP ) eluting forms upon activation .

On DEAE-cellulose chromatography , <protein>[ 3H ] CVZ-receptor complexes</protein> show a shift from high ( 0.25 M KP ) to low salt ( 0.09 M KP ) eluting forms upon activation .


CVZ competes for a 97 , 000-dalton protein labeled by [ 3H ] dexamethasone mesylate .


Scatchard analysis of the binding of [ 3H ] CVZ in glucocorticoid-sensitive cells revealed a curvilinear plot which resolved into high ( 0.4 nM ) and low ( 11 nM ) affinity components .

Scatchard analysis of the binding of [ 3H ] CVZ in <cell_line>glucocorticoid-sensitive cells</cell_line> revealed a curvilinear plot which resolved into high ( 0.4 nM ) and low ( 11 nM ) affinity components .


The receptor concentration of the low affinity site ( 0.30 pmol/mg protein ) was approximately twice that of the high affinity site ( 0.14 pmol/mg protein ) .

The receptor concentration of the low affinity site ( 0.30 pmol/mg protein ) was approximately twice that of the <protein>high affinity site</protein> ( 0.14 pmol/mg protein ) .


Dissociation experiments with dilution and/or excess unlabeled CVZ supported the presence of independent sites .


In contrast , the binding of [ 3H ] DEX to C7 cytosol revealed a single class of binding sites ( Kd = 1.9 nM ; receptor concentration , 0.46 pmol/mg protein ) .


Examination of the binding of [ 3H ] CVZ using 10 ( -5 ) M DEX as the competing ligand showed that DEX binds only to the low affinity site detected by [ 3H ] CVZ .


In cytosol from a glucocorticoid-resistant cell line with virtually no [ 3H ] DEX binding , [ 3H ] CVZ detected a single high affinity binding site that was similar in dissociation constant ( 0.8 nM ) and receptor concentration ( 0.13 pmol/mg protein ) to the high affinity site detected in the glucocorticoid-sensitive cell line C7 .

In cytosol from a <cell_line>glucocorticoid-resistant cell line</cell_line> with virtually no [ 3H ] DEX binding , [ 3H ] CVZ detected a single <protein>high affinity binding site</protein> that was similar in dissociation constant ( 0.8 nM ) and receptor concentration ( 0.13 pmol/mg protein ) to the <protein>high affinity site</protein> detected in the <cell_line>glucocorticoid-sensitive cell line</cell_line> <cell_line>C7</cell_line> .


A controlled pore glass bead assay for the measurement of cytoplasmic and nuclear glucocorticoid receptors .

A controlled pore glass bead assay for the measurement of <protein>cytoplasmic and nuclear glucocorticoid receptors</protein> .


An assay for the quantitation of cytoplasmic and nuclear glucocorticoid receptors in lymphoid tissue has been developed using controlled pore glass ( CPG ) beads .

An assay for the quantitation of <protein>cytoplasmic and nuclear glucocorticoid receptors</protein> in lymphoid tissue has been developed using controlled pore glass ( CPG ) beads .


Soluble receptor -- 3H-steroid complex ( cytosol or nuclear extract ) is adsorbed quantitatively within the crevasses of porous glass beads .

Soluble <protein>receptor -- 3H-steroid complex</protein> ( cytosol or nuclear extract ) is adsorbed quantitatively within the crevasses of porous glass beads .


Excess labeled steroid as well as most non-specifically bound steroid is easily washed away , leaving the hormone-receptor complex retained by the beads .

Excess labeled steroid as well as most non-specifically bound steroid is easily washed away , leaving the <protein>hormone-receptor complex</protein> retained by the beads .


Bound 3H-steroid is eluted with ethanol and measured for radioactivity .


This procedure which is simple , rapid , and highly reproducible is carried out using frozen samples ( stable for many months ) containing as few as 1 X 10 ( 7 ) cells .


A comparison of the CPG assay to dextran coated charcoal and a whole cell assay demonstrates that CPG and dextran coated charcoal give equivalent measurements of cytosolic receptor concentration , while the CPG and whole cell assays provide equivalent values for total receptor content .

A comparison of the CPG assay to dextran coated charcoal and a whole cell assay demonstrates that CPG and dextran coated charcoal give equivalent measurements of <protein>cytosolic receptor</protein> concentration , while the CPG and whole cell assays provide equivalent values for total receptor content .


Plasmacytoid blast crisis in B-cell chronic lymphocytic leukemia : effect of estradiol on growth and differentiation in vitro .

Plasmacytoid blast crisis in <cell_type>B-cell</cell_type> chronic lymphocytic leukemia : effect of estradiol on growth and differentiation in vitro .


Evolution of a case of chronic lymphocytic leukemia ( CLL ) into blast crisis was found to be characterized by three unusual features ( 1 ) the phenotype of the emerging blast cells was that of pre-plasmacytoid cells as shown by plasma cell morphology and an immunological phenotype corresponding partially with CLL- or intermediate B-cells , partially with plasma cells ( terminal transferase - , common acute lymphocytic leukemia antigen - , Ia+ , surface immunoglobulin heavy chains - , surface kappa light chains + , intracytoplasmic immunoglobulin A+ and G+ , BA-1+ , polyclonal gammaglobulin production ) ; ( 2 ) cytogenetic analysis of spontaneous metaphases revealed that in addition to the typical CLL abnormality , trisomy 12 , in all of the cells , an additional translocation between chromosomes 14 and 17 was present in 40 % with a presumptive breakpoint on chromosome 14 ( q12-3 ) never described before ( commonly q32 ) and ( 3 ) the progression of the disease was associated with a striking increase in the expression by the transformed cells of specific binding sites for estradiol ( E2 ) due to an actual increase in total cellular receptor proteins and not to a change in receptor affinity for E2 .

Evolution of a case of chronic lymphocytic leukemia ( CLL ) into blast crisis was found to be characterized by three unusual features ( 1 ) the phenotype of the <cell_type>emerging blast cells</cell_type> was that of <cell_type>pre-plasmacytoid cells</cell_type> as shown by plasma cell morphology and an immunological phenotype corresponding partially with <cell_type>CLL- or intermediate B-cells</cell_type> , partially with <cell_type>plasma cells</cell_type> ( <protein>terminal transferase</protein> - , common <protein>acute lymphocytic leukemia antigen</protein> - , <protein>Ia+</protein> , <protein>surface immunoglobulin heavy chains</protein> - , <protein>surface kappa light chains</protein> + , <protein>intracytoplasmic immunoglobulin A+ and G+</protein> , <protein>BA-1+</protein> , polyclonal gammaglobulin production ) ; ( 2 ) cytogenetic analysis of spontaneous metaphases revealed that in addition to the typical CLL abnormality , trisomy 12 , in all of the cells , an additional translocation between <dna>chromosomes 14 and 17</dna> was present in 40 % with a presumptive breakpoint on <dna>chromosome 14</dna> ( q12-3 ) never described before ( commonly q32 ) and ( 3 ) the progression of the disease was associated with a striking increase in the expression by the <cell_type>transformed cells</cell_type> of specific binding sites for estradiol ( E2 ) due to an actual increase in total <protein>cellular receptor proteins</protein> and not to a change in receptor affinity for E2 .


The functional status of the steroid receptors was confirmed by nuclear transfer of the cytoplasmic hormone-receptor complex upon temperature activation .

The functional status of the <protein>steroid receptors</protein> was confirmed by nuclear transfer of the <protein>cytoplasmic hormone-receptor complex</protein> upon temperature activation .


Since the rise in E2-receptor display paralleled a large increase in the proliferative activity of the cells as well as a change in their maturation status the question was raised as to whether the E2-receptor should be considered as a physiological marker of growth rate or of cellular differentiation .

Since the rise in <protein>E2-receptor</protein> display paralleled a large increase in the proliferative activity of the cells as well as a change in their maturation status the question was raised as to whether the <protein>E2-receptor</protein> should be considered as a physiological marker of growth rate or of cellular differentiation .


Exposure of the patient 's blast cells to E2 in vitro resulted in cessation of cell growth following at least one mitosis after addition of the inducer as seen from the replacement of the large blasts by small CLL-like cells without definite signs of alteration of the differentiation status .

Exposure of the patient 's <cell_type>blast cells</cell_type> to E2 in vitro resulted in cessation of cell growth following at least one mitosis after addition of the inducer as seen from the replacement of the <cell_type>large blasts</cell_type> by small <cell_type>CLL-like cells</cell_type> without definite signs of alteration of the differentiation status .


This suggests the association of E2-receptor expression with control of growth rather than cell maturation .

This suggests the association of <protein>E2-receptor</protein> expression with control of growth rather than cell maturation .


Multiple forms and fragments of cytosolic glucocorticoid receptors from human leukemic cells and normal lymphocytes .

Multiple forms and fragments of <protein>cytosolic glucocorticoid receptors</protein> from <cell_type>human leukemic cells</cell_type> and <cell_type>normal lymphocytes</cell_type> .


Therapy with glucocorticoids is generally more effective in acute lymphoblastic leukemia than in other types of human leukemia .


Previous studies , however , have not revealed any consistent relationship between clinical responsiveness and the cellular or cytosolic concentration of glucocorticoid-binding sites .

Previous studies , however , have not revealed any consistent relationship between clinical responsiveness and the cellular or cytosolic concentration of <protein>glucocorticoid-binding sites</protein> .


The objectives of this study were to determine whether there are intrinsic structural differences among the glucocorticoid receptors in various types of leukemic cells and normal lymphocytes and to investigate the role of endogenous peptidases in receptor degradation .

The objectives of this study were to determine whether there are intrinsic structural differences among the <protein>glucocorticoid receptors</protein> in various types of <cell_type>leukemic cells</cell_type> and <cell_type>normal lymphocytes</cell_type> and to investigate the role of <protein>endogenous peptidases</protein> in receptor degradation .


Cytosols were prepared from fresh or rapidly frozen leukocytes from 6 healthy adults and 35 high-risk leukemia patients ( median white blood cell count , 150 , 000 cells/microliter ; median age , 13 years ) .

Cytosols were prepared from <cell_type>fresh or rapidly frozen leukocytes</cell_type> from 6 healthy adults and 35 high-risk leukemia patients ( median white blood cell count , 150 , 000 cells/microliter ; median age , 13 years ) .


Receptors were labeled with [ 3H ] triamcinolone acetonide and quantitated by charcoal-dextran treatment or Sephadex LH-20 chromatography .


Mean and median cytosolic receptor concentrations in 12 acute lymphoblastic leukemia specimens lacking the standard B-cell or T-cell markers ( `` null cells '' ) were approximately 4-fold higher than in 23 other leukemic cell specimens .

Mean and median cytosolic receptor concentrations in 12 acute lymphoblastic leukemia specimens lacking the standard B-cell or T-cell markers ( `` null cells '' ) were approximately 4-fold higher than in 23 other <cell_type>leukemic cell specimens</cell_type> .


No other consistent differences in receptor content were observed .


Agarose filtration and ultracentrifugation in hypotonic buffers containing 20 mM Na2MoO4 revealed complexes of similar size and shape in all clinical specimens tested and two established leukemic cell lines .

Agarose filtration and ultracentrifugation in hypotonic buffers containing 20 mM Na2MoO4 revealed complexes of similar size and shape in all clinical specimens tested and two established <cell_line>leukemic cell lines</cell_line> .


They had Stokes radii ( Rs ) of 8.1 +/- 0.5 ( S.D. ) nm ( n = 50 ) , sedimentation coefficients of 9.5 +/- 0.3S ( n = 40 ) , molecular weights of approximately 330 , 000 , and axial ratios ( a/b ) of approximately 12 .


In hypertonic , molybdate-free buffer , these oligomeric complexes were dissociated into subunits with Rs of 5.9 +/- 0.3 nm ( n = 12 ) and a/b of 11 to 12 , as observed previously for other receptors .

In hypertonic , molybdate-free buffer , these <protein>oligomeric complexes</protein> were dissociated into subunits with Rs of 5.9 +/- 0.3 nm ( n = 12 ) and a/b of 11 to 12 , as observed previously for other receptors .


Fragmentation of the oligomer and the subunit was evident in some cytosols .

Fragmentation of the <protein>oligomer</protein> and the <protein>subunit</protein> was evident in some cytosols .


High activities of peptidases of various specificities were detected in leukemic cell cytosols , as in other cytosols , by fluorometric assays with derivatives of 7-amino-4-methylcoumarin .

High activities of <protein>peptidases</protein> of various specificities were detected in leukemic cell cytosols , as in other cytosols , by fluorometric assays with derivatives of 7-amino-4-methylcoumarin .


Receptor cleavage by these and other endogenous enzymes may account for previous observations of `` abnormal '' receptors in cytosols from some leukemic specimens .

Receptor cleavage by these and other <protein>endogenous enzymes</protein> may account for previous observations of `` abnormal '' receptors in cytosols from some <cell_type>leukemic specimens</cell_type> .


We conclude that intrinsic structural defects in the receptors are unlikely explanations for the unresponsiveness of some types of leukemia to steroid therapy .


Glucocorticoid receptor number and intracellular water space .

<protein>Glucocorticoid receptor</protein> number and intracellular water space .


In order to elucidate the relationship between cell water content and number of glucocorticoid receptors , eleven normal and malignant lymphoid or myelomonocytic cell types originating from mouse , rat and man were investigated .

In order to elucidate the relationship between cell water content and number of <protein>glucocorticoid receptors</protein> , eleven normal and <cell_type>malignant lymphoid or myelomonocytic cell types</cell_type> originating from mouse , rat and man were investigated .


The cellular water space was measured with 3H2O , and glucocorticoid receptor number was measured in a whole-cell binding assay with [ 3H ] dexamethasone at 30 and 37 degrees C .

The cellular water space was measured with 3H2O , and <protein>glucocorticoid receptor</protein> number was measured in a whole-cell binding assay with [ 3H ] dexamethasone at 30 and 37 degrees C .


The intracellular water phase concentration of glucocorticoid receptors ( around 40 nmol/l cell water ) , and the dependence of receptor affinity on temperature were similar in normal and malignant rodent and human cells .

The intracellular water phase concentration of <protein>glucocorticoid receptors</protein> ( around 40 nmol/l cell water ) , and the dependence of receptor affinity on temperature were similar in <cell_type>normal and malignant rodent and human cells</cell_type> .


It is concluded that comparisons of glucocorticoid receptor levels are best made on the basis of intracellular receptor concentrations .

It is concluded that comparisons of <protein>glucocorticoid receptor</protein> levels are best made on the basis of <protein>intracellular receptor</protein> concentrations .


Covalent labeling of rat thymocyte and human lymphoid glucocorticoid receptor .

Covalent labeling of <cell_type>rat thymocyte</cell_type> and <protein>human lymphoid glucocorticoid receptor</protein> .


Lymphoid cells contain specific receptors for glucocorticoids .

<cell_type>Lymphoid cells</cell_type> contain specific <protein>receptors</protein> for glucocorticoids .


We have used [ 3H ] dexamethasone-21-mesylate to label covalently glucocorticoid receptors in rat thymic lymphocytes and in neoplastic cells obtained from patients with acute lymphoblastic leukemia and malignant lymphoma .

We have used [ 3H ] dexamethasone-21-mesylate to label covalently <protein>glucocorticoid receptors</protein> in <cell_type>rat thymic lymphocytes</cell_type> and in <cell_type>neoplastic cells</cell_type> obtained from patients with acute lymphoblastic leukemia and malignant lymphoma .


The covalently labeled glucocorticoid receptors were identified by polyacrylamide gel electrophoresis ( in the presence of 0.1 % sodium dodecyl sulfate ) .

The covalently labeled <protein>glucocorticoid receptors</protein> were identified by polyacrylamide gel electrophoresis ( in the presence of 0.1 % sodium dodecyl sulfate ) .


In cytosolic fractions prepared from rat thymic lymphocytes , [ 3H ] -dexamethasone-21-mesylate labels a protein ( Mr approximately equal to 95 , 000 ) which was identified as the glucocorticoid receptor by the following criteria : ( a ) labeling of this moiety is inhibited by treatment with a 100-fold molar excess of glucocorticoids , such as dexamethasone and triamcinolone acetonide ; and ( b ) the covalently labeled Mr approximately equal to 95 , 000 protein is activated ( by heating at 20 degrees for 30 min ) to a form that binds to DNA-cellulose .

In cytosolic fractions prepared from <cell_type>rat thymic lymphocytes</cell_type> , [ 3H ] -dexamethasone-21-mesylate labels a protein ( Mr approximately equal to 95 , 000 ) which was identified as the <protein>glucocorticoid receptor</protein> by the following criteria : ( a ) labeling of this moiety is inhibited by treatment with a 100-fold molar excess of glucocorticoids , such as dexamethasone and triamcinolone acetonide ; and ( b ) the covalently labeled Mr approximately equal to 95 , 000 protein is activated ( by heating at 20 degrees for 30 min ) to a form that binds to DNA-cellulose .


When intact thymocytes are treated with [ 3H ] dexamethasone-21-mesylate , an Mr approximately equal to 95 , 000 moiety is also labeled covalently .

When <cell_type>intact thymocytes</cell_type> are treated with [ 3H ] dexamethasone-21-mesylate , an Mr approximately equal to 95 , 000 moiety is also labeled covalently .


Approximately 35 % of the glucocorticoid receptors can be labeled covalently when intact thymocytes are treated with 100 nM [ 3H ] dexamethasone-21-mesylate for 30 min at 4 degrees .

Approximately 35 % of the <protein>glucocorticoid receptors</protein> can be labeled covalently when intact <cell_type>thymocytes</cell_type> are treated with 100 nM [ 3H ] dexamethasone-21-mesylate for 30 min at 4 degrees .


Neoplastic cells from acute lymphoblastic leukemia and malignant lymphoma were treated with [ 3H ] dexamethasone-21-mesylate .

<cell_type>Neoplastic cells</cell_type> from acute lymphoblastic leukemia and malignant lymphoma were treated with [ 3H ] dexamethasone-21-mesylate .


In all samples , an Mr approximately equal to 95 , 000 moiety was labeled covalently ; labeling was inhibited by excess glucocorticoid .


Smaller moieties were also identified by competition experiments ; these may represent proteolytic fragments of the Mr approximately equal to 95 , 000 receptor .

<protein>Smaller moieties</protein> were also identified by competition experiments ; these may represent <protein>proteolytic fragments</protein> of the Mr approximately equal to 95 , 000 receptor .


Thus , in rat and human lymphoid cells , [ 3H ] dexamethasone-21-mesylate can be used to label covalently the glucocorticoid receptor .

Thus , in <cell_type>rat and human lymphoid cells</cell_type> , [ 3H ] dexamethasone-21-mesylate can be used to label covalently the <protein>glucocorticoid receptor</protein> .


The association of cytosol oestrogen and progesterone receptors with histological features of breast cancer and early recurrence of disease .

The association of cytosol <protein>oestrogen and progesterone receptors</protein> with histological features of breast cancer and early recurrence of disease .


Two hundred and eighty-eight primary breast tumours were examined for the presence or absence of oestrogen ( REc ) and progesterone ( RPc ) receptors .

Two hundred and eighty-eight primary breast tumours were examined for the presence or absence of <protein>oestrogen ( REc ) and progesterone ( RPc ) receptors</protein> .


Analysis has shown a relative interdependence between the steroid receptor status of primary breast cancer and other prognostic variables such as histological grade , lymphocytic infiltration and tumour elastosis .

Analysis has shown a relative interdependence between the <protein>steroid receptor</protein> status of primary breast cancer and other prognostic variables such as histological grade , lymphocytic infiltration and tumour elastosis .


There were significant associations between epithelial cellularity , stromal fibrosis and the value of REc in those tumours in which the receptor was present .

There were significant associations between epithelial cellularity , stromal fibrosis and the value of <protein>REc</protein> in those tumours in which the receptor was present .


Cellularity and fibrosis were unrelated to the presence or absence of oestrogen receptor .

Cellularity and fibrosis were unrelated to the presence or absence of <protein>oestrogen receptor</protein> .


By contrast , neither the presence or absence nor the value of RPc could be related to cellularity or fibrosis .

By contrast , neither the presence or absence nor the value of <protein>RPc</protein> could be related to cellularity or fibrosis .


The value of REc and RPc analysis as an indicator of prognosis was examined in a sub-group of 175 patients receiving no additional treatment following mastectomy .

The value of <protein>REc</protein> and <protein>RPc</protein> analysis as an indicator of prognosis was examined in a sub-group of 175 patients receiving no additional treatment following mastectomy .


Overall relapse-free survival ( RFS ) was no different for those patients with receptors compared to those without them ( REc P = 0.11 , RPc P = 0.7 ) .

Overall relapse-free survival ( RFS ) was no different for those patients with receptors compared to those without them ( <protein>REc</protein> P = 0.11 , RPc P = 0.7 ) .


There was no difference in RFS of receptor positive and negative tumours when the axillary node status was taken into account .


Clinical implications of glucocorticoid receptors in human leukemia .

Clinical implications of <protein>glucocorticoid receptors</protein> in human leukemia .


Normal lymphoid cells contain glucocorticoid receptor .

<cell_type>Normal lymphoid cells</cell_type> contain <protein>glucocorticoid receptor</protein> .


A variety of stimuli that activate these cells also induce increases in receptor concentration .


Similar glucocorticoid receptors can be detected in lymphoid cells from patients with acute lymphoblastic leukemia ( ALL ) .

Similar <protein>glucocorticoid receptors</protein> can be detected in <cell_type>lymphoid cells</cell_type> from patients with acute lymphoblastic leukemia ( ALL ) .


Absence of the glucocorticoid receptor ( usually found in treated patients ) predicts lack of glucocorticoid responsiveness .

Absence of the <protein>glucocorticoid receptor</protein> ( usually found in treated patients ) predicts lack of glucocorticoid responsiveness .


Furthermore , in our hands , glucocorticoid receptor levels correlate with the duration of complete remission in ALL ( though not in other forms of leukemia ) .

Furthermore , in our hands , <protein>glucocorticoid receptor</protein> levels correlate with the duration of complete remission in ALL ( though not in other forms of leukemia ) .


This association is independent of cell type , age , sex , or initial leukocyte count .

This association is independent of cell type , age , sex , or initial <cell_type>leukocyte</cell_type> count .


The level of receptor shows a negative correlation with increasing aggressiveness of the tumor ( null-cell leukemia greater than T-cell leukemia greater than Burkitt 's lymphoma ) .


Corticosteroid-mediated immunoregulation in man .


Glucocorticoids have profound and complex effects on the human immune response .


However , the precise mechanisms of the corticosteroid-induced immunoregulation in man have not been precisely defined .


Intracytoplasmic corticosteroid-specific receptors appear to be an important common pathway for steroid-induced changes , but variations of receptor parameters do not account for the multifaceted effects on the immune system .

<protein>Intracytoplasmic corticosteroid-specific receptors</protein> appear to be an important common pathway for steroid-induced changes , but variations of receptor parameters do not account for the multifaceted effects on the immune system .


Human circulating mononuclear cells redistribute out of the intravascular compartment following treatment with corticosteroids .

<cell_type>Human circulating mononuclear cells</cell_type> redistribute out of the intravascular compartment following treatment with corticosteroids .


Although certain components at this redistribution phenomenon have been well-characterized , the importance of this compartmental cellular shift with respect to the mechanisms of corticosteroid-induced immunoregulation are less well-defined .


Recent observations that activated lymphocytes may be sensitive to the lytic effects of glucocorticoids suggest that under certain situations the elimination of selected subsets of cells may be a relevant mechanism of corticosteroid-mediated immunoregulation in man .

Recent observations that <cell_type>activated lymphocytes</cell_type> may be sensitive to the lytic effects of glucocorticoids suggest that under certain situations the elimination of selected subsets of cells may be a relevant mechanism of corticosteroid-mediated immunoregulation in man .


Corticosteroid-mediated effects on monocyte function may be an important mechanism of drug-induced immunoregulation in monocyte-dependent responses .

Corticosteroid-mediated effects on <cell_type>monocyte</cell_type> function may be an important mechanism of <cell_type>drug-induced immunoregulation</cell_type> in <cell_type>monocyte-dependent responses</cell_type> .


In some experimental conditions , corticosteroids inhibit Interleukin 1 production by monocytes .

In some experimental conditions , corticosteroids inhibit <protein>Interleukin 1</protein> production by <cell_type>monocytes</cell_type> .


The immunoregulatory effects of corticosteroids on lymphocyte immune responses are complex .

The immunoregulatory effects of corticosteroids on <cell_type>lymphocyte</cell_type> immune responses are complex .


In vitro corticosteroids appear to selectively affect early immunoregulatory events as opposed to altering an established response .


Multiple sites of steroid-induced modulations of human B cell responses have been defined .

Multiple sites of steroid-induced modulations of <cell_type>human B cell</cell_type> responses have been defined .


Human lymphoid cell lines and glucocorticoids : II .

<cell_line>Human lymphoid cell lines</cell_line> and glucocorticoids : II .


Whole cell and cytoplasmic binding properties of lymphoblastoid , leukaemia and lymphoma lines .

Whole cell and cytoplasmic binding properties of <cell_line>lymphoblastoid , leukaemia and lymphoma lines</cell_line> .


The glucocorticoid binding properties of 18 human lymphoid cell lines ( HLCL ) have been investigated .

The glucocorticoid binding properties of 18 <cell_line>human lymphoid cell lines</cell_line> ( <cell_line>HLCL</cell_line> ) have been investigated .


The specificity of steroid binding was confirmed with various glucocorticoid agonists and antagonists .


A gradation in whole cell and cytoplasmic glucocorticoid binding capacity was observed in the different cell line types : lymphoblastoid greater than lymphoma greater than leukaemia .

A gradation in whole cell and cytoplasmic glucocorticoid binding capacity was observed in the different cell line types : <cell_line>lymphoblastoid</cell_line> greater than <cell_line>lymphoma</cell_line> greater than <cell_line>leukaemia</cell_line> .


The cytoplasmic receptors of leukaemia and lymphoblastoid lines appeared to contain both proteinaceous and phospholipid components .

The <protein>cytoplasmic receptors</protein> of <cell_line>leukaemia and lymphoblastoid lines</cell_line> appeared to contain both proteinaceous and phospholipid components .


Cytoplasmic steroid-receptor complexes exhibited a wide range of sedimentation coefficients ( 8.5-11.3S ) in low ionic strength buffer but there was no correlation with cell line type or glucocorticoid sensitivity .

<protein>Cytoplasmic steroid-receptor complexes</protein> exhibited a wide range of sedimentation coefficients ( 8.5-11.3S ) in low ionic strength buffer but there was no correlation with cell line type or glucocorticoid sensitivity .


Activation of these complexes by heat ( 37 degrees C ) or exposure to high ionic strength buffer ( 0.3 M NaCl ) induced nuclear binding of steroid but only complexes in high ionic strength buffer manifested changes in sedimentation coefficient .


No correlation was observed between the level or nature of glucocorticoid binding and the cytolethal or cytostatic responsiveness of HLCL to glucocorticoid treatment in vitro .

No correlation was observed between the level or nature of glucocorticoid binding and the cytolethal or cytostatic responsiveness of <cell_line>HLCL</cell_line> to glucocorticoid treatment in vitro .


The resistance to cytolethal effects can not be ascribed to a failure of cells to take up and bind steroid or to significant differences in the molecular species of cytoplasmic receptors present .

The resistance to cytolethal effects can not be ascribed to a failure of cells to take up and bind steroid or to significant differences in the molecular species of <protein>cytoplasmic receptors</protein> present .


The molecular mechanisms by which glucocorticoids achieve cytolethal responses in human lymphoid cells

The molecular mechanisms by which glucocorticoids achieve cytolethal responses in <cell_type>human lymphoid cells</cell_type>


CD28 -mediated activation in CD45RA+ and CD45RO+ T cells : enhanced levels of reactive oxygen intermediates and c-Rel nuclear translocation in CD45RA+ cells .

<protein>CD28</protein> -mediated activation in <cell_type>CD45RA+ and CD45RO+ T cells</cell_type> : enhanced levels of reactive oxygen intermediates and <protein>c-Rel</protein> nuclear translocation in <cell_type>CD45RA+ cells</cell_type> .


We have analyzed the effect of complete T cell activation ( anti-CD3 plus anti-CD28 ) on the activation of NF-kappaB in CD45RA+ ( naive ) and CD45RO+ ( memory/effector ) T cells .

We have analyzed the effect of complete T cell activation ( <protein>anti-CD3</protein> plus <protein>anti-CD28</protein> ) on the activation of <protein>NF-kappaB</protein> in <cell_type>CD45RA+ ( naive ) and CD45RO+ ( memory/effector ) T cells</cell_type> .


Long exposure ( 24 h ) induced stronger NF-kappaB DNA binding in CD45RA+ cells than in CD45RO+ cells .

Long exposure ( 24 h ) induced stronger <protein>NF-kappaB</protein> DNA binding in <cell_type>CD45RA+ cells</cell_type> than in <cell_type>CD45RO+ cells</cell_type> .


Analysis of the nuclear c-Rel protein indicated that after anti-CD3+anti-CD28 stimulation the level of c-Rel was higher in CD45RA+ cells .

Analysis of the <protein>nuclear c-Rel protein</protein> indicated that after anti-CD3+anti-CD28 stimulation the level of <protein>c-Rel</protein> was higher in <cell_type>CD45RA+ cells</cell_type> .


Analysis of the cytoplasmic inhibitor IkappaBalpha indicated that anti-CD3+anti-CD28 stimulation induced a long-lasting degradation in CD45RA+ cells but in CD45RO+ cells the degradation process was more rapid .

Analysis of the cytoplasmic inhibitor <protein>IkappaBalpha</protein> indicated that anti-CD3+anti-CD28 stimulation induced a long-lasting degradation in <cell_type>CD45RA+ cells</cell_type> but in <cell_type>CD45RO+ cells</cell_type> the degradation process was more rapid .


Because the CD28 costimulus is known to induce the production of reactive oxygen intermediates ( ROIs ) , the intracellular ROI levels in CD45RA+ and CD45RO+ cells were compared by flow cytometry .

Because the CD28 costimulus is known to induce the production of reactive oxygen intermediates ( ROIs ) , the intracellular ROI levels in <cell_type>CD45RA+ and CD45RO+ cells</cell_type> were compared by flow cytometry .


ROIs were produced in both cell types , but more strongly in CD45RA+ cells .

ROIs were produced in both cell types , but more strongly in <cell_type>CD45RA+ cells</cell_type> .


The data presented in this study further emphasize the differences between CD45RA+ and CD45RO+ T lymphocytes in ROI-dependent signaling pathways .

The data presented in this study further emphasize the differences between <cell_type>CD45RA+ and CD45RO+ T lymphocytes</cell_type> in ROI-dependent signaling pathways .


Ikaros in hemopoietic lineage determination and homeostasis .

<protein>Ikaros</protein> in <cell_line>hemopoietic lineage</cell_line> determination and homeostasis .


Studies on the molecular mechanisms that control hemopoietic differentiation have focused on signaling cascades and nuclear effectors that drive this complex developmental system in a regulated fashion .


Here we review the role of Ikaros , the founding member of a unique family of zinc finger transcription factors in this developmental process .

Here we review the role of <protein>Ikaros</protein> , the founding member of a unique family of <protein>zinc finger transcription factors</protein> in this developmental process .


Studies on an Ikaros null mutation have revealed an essential role for this factor in lymphoid cell fate determination and at subsequent branch points of the T cell differentiation pathway .

Studies on an <protein>Ikaros</protein> null mutation have revealed an essential role for this factor in <cell_type>lymphoid cell</cell_type> fate determination and at subsequent branch points of the <cell_type>T cell</cell_type> differentiation pathway .


Differences in the phenotypes of a null and a dominant negative ( DN ) Ikaros mutation provide insight into a regulatory network through which Ikaros proteins exert their effects in development .

Differences in the phenotypes of a null and a dominant negative ( DN ) Ikaros mutation provide insight into a regulatory network through which <protein>Ikaros proteins</protein> exert their effects in development .


In addition a comparative analysis of the hemopoietic stem cell and precursor compartment resulting from the two Ikaros mutations reveals a profound yet not absolute requirement for Ikaros in the production and differentiation of these populations .

In addition a comparative analysis of the <cell_type>hemopoietic stem cell</cell_type> and precursor compartment resulting from the two <protein>Ikaros</protein> mutations reveals a profound yet not absolute requirement for <protein>Ikaros</protein> in the production and differentiation of these populations .


Overexpression of p65 and c-Jun substitutes for B7-1 costimulation by targeting the CD28RE within the IL-2 promoter .

Overexpression of p65 and c-Jun substitutes for B7-1 costimulation by targeting the <dna>CD28RE</dna> within the <dna>IL-2 promoter</dna> .


The role of Rel and activation protein-1 ( AP-1 ) in IL-2 promoter activity in B7-1- and leukocyte function-associated Ag-3 ( LFA. 3 ) -costimulated T cells has been evaluated .

The role of <protein>Rel</protein> and <protein>activation protein-1</protein> ( <protein>AP-1</protein> ) in <dna>IL-2 promoter</dna> activity in <cell_type>B7-1- and leukocyte function-associated Ag-3 ( LFA. 3 ) -costimulated T cells</cell_type> has been evaluated .


We demonstrate that overexpression of c-Jun but not c-Fos increases IL-2 promoter activity in both B7-1- and LFA-3-costimulated Jurkat T cells .

We demonstrate that overexpression of <protein>c-Jun</protein> but not <protein>c-Fos</protein> increases <dna>IL-2 promoter</dna> activity in both <cell_type>B7-1- and LFA-3-costimulated Jurkat T cells</cell_type> .


Cotransfection of both c-Jun and c-Fos substitutes for B7-1 costimulation in driving an activation protein-1 response element but not for the IL-2 promoter .

Cotransfection of both c-Jun and c-Fos substitutes for B7-1 costimulation in driving an <dna>activation protein-1 response element</dna> but not for the <dna>IL-2 promoter</dna> .


Overexpression of Rel proteins demonstrated that p65-expressing Jurkat cells transcribed equally well a nuclear factor kappabeta reporter construct when costimulated with B7-1 or LFA-3 , but transcription of IL-2 promoter or CD28 response element ( CD28RE ) -driven reporters was superior in B7-1-costimulated cells .

Overexpression of <protein>Rel proteins</protein> demonstrated that <cell_line>p65-expressing Jurkat cells</cell_line> transcribed equally well a <dna>nuclear factor kappabeta reporter construct</dna> when costimulated with <protein>B7-1</protein> or <protein>LFA-3</protein> , but transcription of <dna>IL-2 promoter</dna> or <dna>CD28 response element ( CD28RE ) -driven reporters</dna> was superior in <cell_line>B7-1-costimulated cells</cell_line> .


Combined expression of c-Jun and p65 induced vigorous transcription of IL-2 promoter- and CD28RE-driven reporter constructs in both LFA-3- and B7-1-costimulated Jurkat cells .

Combined expression of <protein>c-Jun</protein> and <protein>p65</protein> induced vigorous transcription of <dna>IL-2 promoter- and CD28RE-driven reporter constructs</dna> in both <cell_type>LFA-3- and B7-1-costimulated Jurkat cells</cell_type> .


Mutating the CD28RE but not the upstream nuclear factor kappabeta-binding site in the IL-2 promoter reduced B7-1 -driven transcription > 90 % .

Mutating the <dna>CD28RE</dna> but not the <dna>upstream nuclear factor kappabeta-binding site</dna> in the <dna>IL-2 promoter</dna> reduced <protein>B7-1</protein> -driven transcription > 90 % .


The results implicates a major role of the CD28RE in the integration of p65 / c-Jun -mediated transcription within the IL-2 promoter .

The results implicates a major role of the <dna>CD28RE</dna> in the integration of <protein>p65</protein> / <protein>c-Jun</protein> -mediated transcription within the <dna>IL-2 promoter</dna> .


We suggest that the transition from an autocrine LFA-3 -driven immune response to a B7 -- induced paracrine immune response involves the activation of c-Jun and p65 , which target the CD28RE region of the IL-2 promoter .

We suggest that the transition from an autocrine <protein>LFA-3</protein> -driven immune response to a B7 -- induced paracrine immune response involves the activation of <protein>c-Jun</protein> and <protein>p65</protein> , which target the <dna>CD28RE</dna> region of the <dna>IL-2 promoter</dna> .


Defects in actin-cap formation in Vav-deficient mice implicate an actin requirement for lymphocyte signal transduction .


BACKGROUND : Antigen-receptor interactions on lymphocytes result in local clustering of actin , receptors and signaling molecules into an asymmetric membrane structure termed a cap .

BACKGROUND : Antigen-receptor interactions on <cell_type>lymphocytes</cell_type> result in local clustering of <protein>actin</protein> , receptors and signaling molecules into an asymmetric membrane structure termed a cap .


Although actin polymerization is known to be required , the mechanisms underlying cap formation are unclear .


We have studied the events underlying cap formation using mice bearing a null mutation in vav ( vav -/- ) , a gene that encodes a guanine-nucleotide exchange factor for the GTPase Rac .

We have studied the events underlying cap formation using mice bearing a null mutation in <dna>vav</dna> ( <dna>vav</dna> -/- ) , a gene that encodes a <protein>guanine-nucleotide exchange factor</protein> for the <protein>GTPase Rac</protein> .


RESULTS : Lymphocytes from vav -/- mice failed to form T-cell receptor caps following activation and had a defective actin cytoskeleton .

RESULTS : <cell_type>Lymphocytes</cell_type> from <dna>vav</dna> -/- mice failed to form T-cell receptor caps following activation and had a defective actin cytoskeleton .


The vav-/- T cells were deficient in interleukin-2 ( IL-2 ) production and proliferation , and the peak of Ca2+ mobilization was reduced although of normal duration .

The <cell_type>vav-/- T cells</cell_type> were deficient in interleukin-2 ( IL-2 ) production and proliferation , and the peak of Ca2+ mobilization was reduced although of normal duration .


Activation of Jun N-terminal kinase or stress-activated kinase ( JNK or SAPK ) and mitogen-activated protein kinase ( MAPK ) and the induction of the transcription factor NF-ATc1 and egr-1 genes was normal .

Activation of <protein>Jun N-terminal kinase</protein> or <protein>stress-activated kinase</protein> ( <protein>JNK</protein> or <protein>SAPK</protein> ) and <protein>mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) and the induction of the <protein>transcription factor</protein> <dna>NF-ATc1 and egr-1 genes</dna> was normal .


Despite the reduced Ca2+ mobilization , translocation of cytoplasmic NF-ATc to the nucleus was normal , reflecting that the lower levels of Ca2+ in vav-/- cells were still sufficient to activate calcineurin .

Despite the reduced Ca2+ mobilization , translocation of <protein>cytoplasmic NF-ATc</protein> to the nucleus was normal , reflecting that the lower levels of Ca2+ in <cell_type>vav-/- cells</cell_type> were still sufficient to activate <protein>calcineurin</protein> .


Treatment of lymphocytes with cytochalasin D , which blocks actin polymerization , inhibited cap formation and produced defects in signaling and IL-2 transcriptional induction in response to antigen-receptor signaling that were nearly identical to those seen in vav-/- cells .

Treatment of <cell_type>lymphocytes</cell_type> with cytochalasin D , which blocks actin polymerization , inhibited cap formation and produced defects in signaling and IL-2 transcriptional induction in response to antigen-receptor signaling that were nearly identical to those seen in <cell_type>vav-/- cells</cell_type> .


In transfection studies , either constitutively active Vav or Rac could complement constitutively active calcineurin to activate NF-AT-dependent transcription .

In transfection studies , either constitutively active <protein>Vav</protein> or <protein>Rac</protein> could complement constitutively active <protein>calcineurin</protein> to activate NF-AT-dependent transcription .


CONCLUSIONS : These results indicate that Vav is required for cap formation in lymphocytes .

CONCLUSIONS : These results indicate that <protein>Vav</protein> is required for cap formation in <cell_type>lymphocytes</cell_type> .


Furthermore , the correlation between cap formation , IL-2 production and proliferation supports the hypothesis that an actin-dependent pathway is a source of specialized growth regulatory signals .


CD14 -dependent activation of human endothelial cells by Bacteroides fragilis outer membrane .

<protein>CD14</protein> -dependent activation of <cell_type>human endothelial cells</cell_type> by Bacteroides fragilis outer membrane .


We studied the capacity of isolated Bacteriodes fragilis outer membrane , B. fragilis NCTC9343 lipopolysaccharide ( LPS ; endotoxin ) , and B. fragilis NCTC9343 capsular polysaccharides to activate human umbilical vein endothelial cell ( HUVEC ) monolayers .


To assess HUVEC activation , E-selectin expression was measured by enzyme-linked immunosorbent assay ( ELISA ) , Northern blot analysis for E-selectin-specific mRNA , and electrophoretic gel mobility shift assay ( EMSA ) for NF-kappa B , a transcription factor necessary for E-selectin gene activation .

To assess HUVEC activation , <protein>E-selectin</protein> expression was measured by enzyme-linked immunosorbent assay ( ELISA ) , Northern blot analysis for <rna>E-selectin-specific mRNA</rna> , and electrophoretic gel mobility shift assay ( EMSA ) for <protein>NF-kappa B</protein> , a <protein>transcription factor</protein> necessary for <dna>E-selectin gene</dna> activation .


Exposure of HUVECs to B. fragilis outer membrane fractions , separated from other components of the B. fragilis cell wall by isopycnic , sucrose gradient centrifugation , significantly increased surface expression of E-selectin and induced functional endothelial cell -dependent leukocyte adhesion .

Exposure of <cell_type>HUVECs</cell_type> to B. fragilis outer membrane fractions , separated from other components of the B. fragilis cell wall by isopycnic , sucrose gradient centrifugation , significantly increased surface expression of <protein>E-selectin</protein> and induced functional <cell_type>endothelial cell</cell_type> -dependent leukocyte adhesion .


B. fragilis outer membranes induced translocation of NF-kappa B to HUVEC nuclei and accumulation of E-selectin mRNA in HUVEC cytoplasm .

B. fragilis outer membranes induced translocation of <protein>NF-kappa B</protein> to HUVEC nuclei and accumulation of <rna>E-selectin mRNA</rna> in HUVEC cytoplasm .


E-selectin expression induced by B. fragilis outer membranes was not blocked by polymixin B .


In contrast , E-selectin expression induced by outer membrane fractions purified from E. coli was competitively inhibited by polymixin B .


Neither purified B. fragilis LPS , a prominent constituent of the outer membrane , nor purified B. fragilis capsular polysaccharides induced HUVEC activation .


Two different monoclonal antibodies directed against human CD14 completely inhibited B. fragilis outer membrane-induced NF-kappa B activation , E-selectin transcription , and E-selectin surface expression .

Two different <protein>monoclonal antibodies</protein> directed against <protein>human CD14</protein> completely inhibited B. fragilis outer membrane-induced <protein>NF-kappa B</protein> activation , E-selectin transcription , and E-selectin surface expression .


We conclude that the outer membrane component of the B. fragilis cell wall contains a proinflammatory factor ( s ) , that is not LPS , which induces human endothelial cell activation by a soluble CD14 -dependent mechanism .

We conclude that the outer membrane component of the B. fragilis cell wall contains a proinflammatory factor ( s ) , that is not LPS , which induces <cell_type>human endothelial cell</cell_type> activation by a soluble <protein>CD14</protein> -dependent mechanism .


NF-kappaB protects HIV-1-infected myeloid cells from apoptosis .

<protein>NF-kappaB</protein> protects HIV-1-infected <cell_type>myeloid cells</cell_type> from apoptosis .


HIV-1 infection of primary monocytic cells and myeloid cell lines results in sustained NF-kappaB activation .

HIV-1 infection of <cell_type>primary monocytic cells</cell_type> and <cell_line>myeloid cell lines</cell_line> results in sustained NF-kappaB activation .


Recently , NF-kappaB induction has been shown to play a role in protecting cells from programmed cell death .


In the present study , we sought to investigate whether constitutive NF-kappaB activity in chronically HIV-1-infected promonocytic U937 ( U9-IIIB ) and myeloblastic PLB-985 ( PLB-IIIB ) cells affects apoptotic signaling .

In the present study , we sought to investigate whether constitutive <protein>NF-kappaB</protein> activity in chronically HIV-1-infected <cell_line>promonocytic U937 ( U9-IIIB ) and myeloblastic PLB-985 ( PLB-IIIB ) cells</cell_line> affects apoptotic signaling .


TNFalpha and cycloheximide caused infected cells to undergo apoptosis more rapidly than parental U937 and PLB-985 cells .

<protein>TNFalpha</protein> and cycloheximide caused infected cells to undergo apoptosis more rapidly than <cell_line>parental U937</cell_line> and <cell_line>PLB-985 cells</cell_line> .


Inhibition of TNFalpha -induced NF-kappaB activation using the antioxidant N-acetylcysteine ( NAC ) resulted in increased apoptosis in both U937 and U9-IIIB cells , while preactivation of NF-kappaB with the non-apoptotic inducer IL-1beta caused a relative decrease in apoptosis .

Inhibition of <protein>TNFalpha</protein> -induced NF-kappaB activation using the antioxidant N-acetylcysteine ( NAC ) resulted in increased apoptosis in both <cell_line>U937 and U9-IIIB cells</cell_line> , while preactivation of <protein>NF-kappaB</protein> with the <protein>non-apoptotic inducer IL-1beta</protein> caused a relative decrease in apoptosis .


Inhibition of constitutive NF-kappaB activity in U9-IIIB and PLB-IIIB cells also induced apoptosis , suggesting that NF-kappaB protects cells from a persistent apoptotic signal .

Inhibition of constitutive <protein>NF-kappaB</protein> activity in <cell_line>U9-IIIB and PLB-IIIB cells</cell_line> also induced apoptosis , suggesting that <cell_type>NF-kappaB protects cells</cell_type> from a persistent apoptotic signal .


TNFalpha plus NAC treatment resulted in a marked decrease in Bcl-2 protein levels in HIV-1-infected cells , coupled with an increase in Bax protein compared to uninfected cells , suggesting that the difference in susceptibility to TNFalpha -induced apoptosis may relate to the differences in relative levels of Bcl-2 and Bax .

<protein>TNFalpha</protein> plus NAC treatment resulted in a marked decrease in <protein>Bcl-2 protein</protein> levels in <cell_type>HIV-1-infected cells</cell_type> , coupled with an increase in <protein>Bax protein</protein> compared to uninfected cells , suggesting that the difference in susceptibility to <protein>TNFalpha</protein> -induced apoptosis may relate to the differences in relative levels of <protein>Bcl-2</protein> and <protein>Bax</protein> .


The protective role of NF-kappaB in blocking TNFalpha- and HIV-1-induced apoptosis was supported by studies in Jurkat T cells engineered to express IkappaB alpha repressor mutants ( TD-IkappaB ) under the control of a tetracycline-responsive promoter .

The protective role of <protein>NF-kappaB</protein> in blocking TNFalpha- and HIV-1-induced apoptosis was supported by studies in <cell_line>Jurkat T cells</cell_line> engineered to express <protein>IkappaB alpha repressor mutants</protein> ( <protein>TD-IkappaB</protein> ) under the control of a <dna>tetracycline-responsive promoter</dna> .


Cells underwent apoptosis in response to TNFalpha only when NF-kappaB activation was inhibited by TD-IkappaB expression .

Cells underwent apoptosis in response to <protein>TNFalpha</protein> only when NF-kappaB activation was inhibited by <protein>TD-IkappaB</protein> expression .


As was observed for the U9-IIIB cells , TNFalpha treatment also induced a marked decrease in Bcl-2 protein levels in TD-IkappaB expressing cells .

As was observed for the <cell_line>U9-IIIB cells</cell_line> , <protein>TNFalpha</protein> treatment also induced a marked decrease in <protein>Bcl-2 protein</protein> levels in <cell_type>TD-IkappaB expressing cells</cell_type> .


These experiments demonstrate that apoptotic signaling is perturbed in HIV-1-infected U9-IIIB cells and indicate that NF-kappaB activation may play an additional protective role against HIV-1-induced apoptosis in myeloid cells .

These experiments demonstrate that apoptotic signaling is perturbed in HIV-1-infected <cell_line>U9-IIIB cells</cell_line> and indicate that NF-kappaB activation may play an additional protective role against HIV-1-induced apoptosis in <cell_type>myeloid cells</cell_type> .


Human normal peripheral blood B-lymphocytes are deficient in DNA-dependent protein kinase activity due to the expression of a variant form of the Ku86 protein .

<cell_type>Human normal peripheral blood B-lymphocytes</cell_type> are deficient in DNA-dependent protein kinase activity due to the expression of a variant form of the <protein>Ku86 protein</protein> .


The heterodimeric Ku protein , which comprises a 86 kDa ( Ku86 ) amd a 70 kDa ( Ku70 ) subunits , is an abundant nuclear DNA-binding protein which binds in vitro to DNA termini without sequence specificity .

The heterodimeric <protein>Ku protein</protein> , which comprises a <protein>86 kDa ( Ku86 )</protein> amd a <protein>70 kDa ( Ku70 ) subunits</protein> , is an abundant <protein>nuclear DNA-binding protein</protein> which binds in vitro to <dna>DNA termini</dna> without sequence specificity .


Ku is the DNA-targeting component of the large catalytic sub-unit of the DNA-dependent protein kinase complex ( DNA-PK [ CS ] ) , that plays a critical role in mammalian double-strand break repair and lymphoid V ( D ) J recombination .

<protein>Ku</protein> is the <protein>DNA-targeting component</protein> of the large <protein>catalytic sub-unit</protein> of the <protein>DNA-dependent protein kinase complex</protein> ( <protein>DNA-PK [ CS ]</protein> ) , that plays a critical role in mammalian double-strand break repair and lymphoid V ( D ) J recombination .


By using electrophoretic mobility shift assays , we demonstrated that in addition to the major Ku x DNA complex usually detected in cell line extracts , a second complex with faster electrophoretic mobility was observed in normal peripheral blood lymphocytes ( PBL ) extracts .

By using electrophoretic mobility shift assays , we demonstrated that in addition to the <protein>major Ku x DNA complex</protein> usually detected in cell line extracts , a second complex with faster electrophoretic mobility was observed in normal <cell_type>peripheral blood lymphocytes</cell_type> ( <cell_type>PBL</cell_type> ) extracts .


The presence of this faster migrating complex was restricted to B cells among the circulating lymphocyte population .

The presence of this <protein>faster migrating complex</protein> was restricted to <cell_type>B cells</cell_type> among the <cell_type>circulating lymphocyte population</cell_type> .


Western blot analysis revealed that B cells express a variant form of the Ku86 protein with an apparent molecular weight of 69 kDa , and not the 86 kDa- full-length protein .

Western blot analysis revealed that <cell_type>B cells</cell_type> express a variant form of the <protein>Ku86 protein</protein> with an apparent molecular weight of 69 kDa , and not the <protein>86 kDa- full-length protein</protein> .


Although the heterodimer Ku70/variant-Ku86 binds to DNA-ends , this altered form of the Ku heterodimer has a decreased ability to recruit the catalytic component of the complex , DNA-PK ( CS ) , which contributes to an absence of detectable DNA-PK activity in B cells .

Although the <protein>heterodimer Ku70/variant-Ku86</protein> binds to <dna>DNA-ends</dna> , this altered form of the <protein>Ku heterodimer</protein> has a decreased ability to recruit the <protein>catalytic component</protein> of the complex , <protein>DNA-PK ( CS )</protein> , which contributes to an absence of detectable DNA-PK activity in <cell_type>B cells</cell_type> .


These data provide a molecular basis for the increased sensitivity of B cells to ionizing radiation and identify a new mechanism of regulation of DNA-PK activity that operates in vivo .

These data provide a molecular basis for the increased sensitivity of <cell_type>B cells</cell_type> to ionizing radiation and identify a new mechanism of regulation of DNA-PK activity that operates in vivo .


Co-stimulation of human peripheral blood mononuclear cells with IL-2 and anti-CD3 monoclonal antibodies induces phosphorylation of CREB .

Co-stimulation of <cell_type>human peripheral blood mononuclear cells</cell_type> with <protein>IL-2</protein> and <protein>anti-CD3 monoclonal antibodies</protein> induces phosphorylation of <protein>CREB</protein> .


Phosphorylation of the cAMP-response element binding protein CREB within 1 h of CD2 but not CD3 cross-linking of human PBMC was recently demonstrated .

Phosphorylation of the <protein>cAMP-response element binding protein CREB</protein> within 1 h of <protein>CD2</protein> but not <protein>CD3</protein> cross-linking of <cell_type>human PBMC</cell_type> was recently demonstrated .


The absence of P-CREB following CD3 cross-linking was unexpected , as other laboratories reported increased phosphorylation of CREB following CD3 cross-linking of the Jurkat lymphocyte cell line .

The absence of <protein>P-CREB</protein> following CD3 cross-linking was unexpected , as other laboratories reported increased phosphorylation of <protein>CREB</protein> following CD3 cross-linking of the <cell_line>Jurkat lymphocyte cell line</cell_line> .


Due to Jurkat T-cells being IL-2-independent , it was postulated that IL-2 might provide a necessary co-stimulus for phosphorylation of CREB in primary lymphocytes .

Due to <cell_line>Jurkat T-cells</cell_line> being IL-2-independent , it was postulated that <protein>IL-2</protein> might provide a necessary co-stimulus for phosphorylation of <protein>CREB</protein> in <cell_type>primary lymphocytes</cell_type> .


Therefore , P-CREB was evaluated following co-stimulation of human PBMC through the IL-2 and CD2 or CD3 receptors .

Therefore , <protein>P-CREB</protein> was evaluated following co-stimulation of <cell_type>human PBMC</cell_type> through the <protein>IL-2 and CD2 or CD3 receptors</protein> .


IL-2 did not further augment phosphorylation of CREB following CD2 cross-linking .

<protein>IL-2</protein> did not further augment phosphorylation of <protein>CREB</protein> following CD2 cross-linking .


However , while neither IL-2 nor CD3 cross-linking alone induced P-CREB , a 4.5-fold increase in phosphorylation of CREB within 1 h of IL-2/CD3 co-stimulation was observed .

However , while neither <protein>IL-2</protein> nor CD3 cross-linking alone induced <protein>P-CREB</protein> , a 4.5-fold increase in phosphorylation of <protein>CREB</protein> within 1 h of IL-2/CD3 co-stimulation was observed .


Phosphorylation was not associated with the induction of cAMP , and inhibition of PKA signaling had no effect on P-CREB .

Phosphorylation was not associated with the induction of cAMP , and inhibition of PKA signaling had no effect on <protein>P-CREB</protein> .


Consistent with signal transduction through p56lck or p59fyn , inhibition of PTK signaling reduced phosphorylation 50 % .

Consistent with signal transduction through <protein>p56lck</protein> or <protein>p59fyn</protein> , inhibition of PTK signaling reduced phosphorylation 50 % .


Interestingly , inhibiting PKC signaling with calphostin C further increased P-CREB levels 3-fold over that observed in IL-2/CD3 co-stimulated cells not pretreated with a PKC inhibitor .

Interestingly , inhibiting PKC signaling with calphostin C further increased P-CREB levels 3-fold over that observed in <cell_type>IL-2/CD3 co-stimulated cells</cell_type> not pretreated with a PKC inhibitor .


In contrast to previous studies performed in the absence of exogenous IL-2 , no increase in binding of CREB to a 32P-labeled oligonucleotide probe was observed by electrophoretic mobility shift assay .

In contrast to previous studies performed in the absence of <protein>exogenous IL-2</protein> , no increase in binding of <protein>CREB</protein> to a 32P-labeled oligonucleotide probe was observed by electrophoretic mobility shift assay .


These data suggest that the IL-2 and CD3 signaling pathways provide a necessary and co-operative stimulus promoting phosphorylation of CREB following receptor cross-linking .

These data suggest that the <protein>IL-2</protein> and <protein>CD3</protein> signaling pathways provide a necessary and co-operative stimulus promoting phosphorylation of <protein>CREB</protein> following receptor cross-linking .


HIV-1 infection induces a selective reduction in STAT5 protein expression .


HIV-1 infection is accompanied by qualitative and quantitative defects in CD4+ T lymphocytes .

HIV-1 infection is accompanied by qualitative and quantitative defects in <cell_type>CD4+ T lymphocytes</cell_type> .


Loss of immune function in HIV patients is usually associated with a profound dysregulation of cytokine production .

Loss of immune function in HIV patients is usually associated with a profound dysregulation of <protein>cytokine</protein> production .


To investigate whether cytokine signaling defects occur during HIV infection , PHA blasts from healthy human donors were infected with two strains of HIV-1 and screened for the expression of STAT proteins used in cytokine signaling .

To investigate whether <protein>cytokine</protein> signaling defects occur during HIV infection , <cell_type>PHA blasts</cell_type> from healthy human donors were infected with two strains of HIV-1 and screened for the expression of <protein>STAT proteins</protein> used in <protein>cytokine</protein> signaling .


A selective decrease in STAT5B was seen 8 days after infection with the BZ167 dual-tropic HIV isolate , but not with the Ba-L , M-tropic strain .

A selective decrease in <protein>STAT5B</protein> was seen 8 days after infection with the BZ167 dual-tropic HIV isolate , but not with the Ba-L , M-tropic strain .


Based on these findings , purified T cells from HIV-infected patients in different stages of disease were also tested for STAT expression ; decreases in STAT5A , STAT5B , and STAT1alpha were observed in all patients .

Based on these findings , <cell_type>purified T cells</cell_type> from HIV-infected patients in different stages of disease were also tested for STAT expression ; decreases in <protein>STAT5A</protein> , <protein>STAT5B</protein> , and <protein>STAT1alpha</protein> were observed in all patients .


The reduction in STATs seen in vivo and in vitro after HIV infection may contribute to the loss of T cell function in HIV disease .

The reduction in <protein>STATs</protein> seen in vivo and in vitro after HIV infection may contribute to the loss of <cell_type>T cell</cell_type> function in HIV disease .


Transcription factors that regulate monocyte / macrophage differentiation .

<protein>Transcription factors</protein> that regulate <cell_type>monocyte</cell_type> / <cell_type>macrophage</cell_type> differentiation .


Although all the cells in an organism contain the same genetic information , differences in the cell phenotype arise from the expression of lineage-specific genes .

Although all the cells in an organism contain the same genetic information , differences in the cell phenotype arise from the expression of <dna>lineage-specific genes</dna> .


During myelopoiesis , external differentiating signals regulate the expression of a set of transcription factors .

During myelopoiesis , external differentiating signals regulate the expression of a set of <protein>transcription factors</protein> .


The combined action of these transcription factors subsequently determines the expression of myeloid-specific genes and the generation of monocytes and macrophages .

The combined action of these <protein>transcription factors</protein> subsequently determines the expression of <dna>myeloid-specific genes</dna> and the generation of <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> .


In particular , the transcription factor PU.1 has a critical role in this process .

In particular , the <protein>transcription factor PU.1</protein> has a critical role in this process .


We review the contribution of several transcription factors to the control of macrophage development

We review the contribution of several <protein>transcription factors</protein> to the control of <cell_type>macrophage</cell_type> development


Transcription factor LKLF is sufficient to program T cell quiescence via a c-Myc -- dependent pathway .

<protein>Transcription factor LKLF</protein> is sufficient to program T cell quiescence via a c-Myc -- dependent pathway .


T lymphocytes circulate in a quiescent state until they encounter cognate antigen bound to the surface of an antigen-presenting cell .

<cell_type>T lymphocytes</cell_type> circulate in a quiescent state until they encounter <protein>cognate antigen</protein> bound to the surface of an <cell_type>antigen-presenting cell</cell_type> .


The molecular pathways that regulate T cell quiescence remain largely unknown .


Here we show that forced expression of the lung Kruppel-like transcription factor ( LKLF ) in Jurkat T cells is sufficient to program a quiescent phenotype characterized by decreased proliferation , reduced cell size and protein synthesis and decreased surface expression of activation markers .

Here we show that forced expression of the <protein>lung Kruppel-like transcription factor</protein> ( <protein>LKLF</protein> ) in <cell_line>Jurkat T cells</cell_line> is sufficient to program a quiescent phenotype characterized by decreased proliferation , reduced cell size and protein synthesis and decreased surface expression of activation markers .


Conversely , LKLF-deficient peripheral T cells produced by gene targeting showed increased proliferation , increased cell size and enhanced expression of surface activation markers in vivo .

Conversely , <cell_type>LKLF-deficient peripheral T cells</cell_type> produced by gene targeting showed increased proliferation , increased cell size and enhanced expression of surface activation markers in vivo .


LKLF appeared to function , at least in part , by decreasing expression of the proto-oncogene encoding c-Myc .

<protein>LKLF</protein> appeared to function , at least in part , by decreasing expression of the <dna>proto-oncogene</dna> encoding <protein>c-Myc</protein> .


Forced expression of LKLF was associated with markedly decreased c-Myc expression .

Forced expression of <protein>LKLF</protein> was associated with markedly decreased <protein>c-Myc</protein> expression .


In addition , many effects of LKLF expression were mimicked by expression of the dominant-negative MadMyc protein and rescued by overexpression of c-Myc .

In addition , many effects of <protein>LKLF</protein> expression were mimicked by expression of the <protein>dominant-negative MadMyc protein</protein> and rescued by overexpression of <protein>c-Myc</protein> .


Thus , LKLF is both necessary and sufficient to program quiescence in T cells and functions , in part , by negatively regulating a c-Myc -- dependent pathway .

Thus , <protein>LKLF</protein> is both necessary and sufficient to program quiescence in <cell_type>T cells</cell_type> and functions , in part , by negatively regulating a c-Myc -- dependent pathway .


HTLV-1 p12 ( I ) protein enhances STAT5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells .

<protein>HTLV-1 p12 ( I ) protein</protein> enhances STAT5 activation and decreases the <protein>interleukin-2</protein> requirement for proliferation of <cell_type>primary human peripheral blood mononuclear cells</cell_type> .


The p12 ( I ) protein , encoded by the pX open reading frame I of the human T-lymphotropic virus type 1 ( HTLV-1 ) , is a hydrophobic protein that localizes to the endoplasmic reticulum and the Golgi .

The <protein>p12 ( I ) protein</protein> , encoded by the <dna>pX open reading frame I</dna> of the human T-lymphotropic virus type 1 ( HTLV-1 ) , is a <protein>hydrophobic protein</protein> that localizes to the endoplasmic reticulum and the Golgi .


Although p12 ( I ) contains 4 minimal proline-rich , src homology 3-binding motifs ( PXXP ) , a characteristic commonly found in proteins involved in signaling pathways , it has not been known whether p12 ( I ) has a role in modulating intracellular signaling pathways .

Although <protein>p12 ( I )</protein> contains 4 minimal proline-rich , <protein>src homology 3-binding motifs</protein> ( <protein>PXXP</protein> ) , a characteristic commonly found in proteins involved in signaling pathways , it has not been known whether <protein>p12 ( I )</protein> has a role in modulating intracellular signaling pathways .


This study demonstrated that p12 ( I ) binds to the cytoplasmic domain of the interleukin-2 receptor ( IL-2R ) beta chain that is involved in the recruitment of the Jak1 and Jak3 kinases .

This study demonstrated that <protein>p12 ( I )</protein> binds to the <protein>cytoplasmic domain</protein> of the <protein>interleukin-2 receptor ( IL-2R ) beta chain</protein> that is involved in the recruitment of the <protein>Jak1 and Jak3 kinases</protein> .


As a result of this interaction , p12 ( I ) increases signal transducers and activators of transcription 5 ( STAT5 ) DNA binding and transcriptional activity and this effect depends on the presence of both IL-2R beta and gamma ( c ) chains and Jak3 .

As a result of this interaction , <protein>p12 ( I )</protein> increases <protein>signal transducers and activators of transcription 5</protein> ( <protein>STAT5</protein> ) DNA binding and transcriptional activity and this effect depends on the presence of both <protein>IL-2R beta and gamma ( c ) chains</protein> and <protein>Jak3</protein> .


Transduction of primary human peripheral blood mononuclear cells ( PBMCs ) with a human immunodeficiency virus type 1-based retroviral vector expressing p12 ( I ) also resulted in increased STAT5 phosphorylation and DNA binding .

Transduction of <cell_line>primary human peripheral blood mononuclear cells</cell_line> ( <cell_type>PBMCs</cell_type> ) with a <dna>human immunodeficiency virus type 1-based retroviral vector</dna> expressing <protein>p12 ( I )</protein> also resulted in increased <protein>STAT5</protein> phosphorylation and DNA binding .


However , p12 ( I ) could increase proliferation of human PBMCs only after stimulation of T-cell receptors by treatment of cells with low concentrations of alphaCD3 and alphaCD28 antibodies .

However , <protein>p12 ( I )</protein> could increase proliferation of <cell_type>human PBMCs</cell_type> only after stimulation of <protein>T-cell receptors</protein> by treatment of cells with low concentrations of <protein>alphaCD3 and alphaCD28 antibodies</protein> .


In addition , the proliferative advantage of p12 ( I ) -transduced PBMCs was evident mainly at low concentrations of IL-2 .

In addition , the proliferative advantage of <cell_type>p12 ( I ) -transduced PBMCs</cell_type> was evident mainly at low concentrations of <protein>IL-2</protein> .


Together , these data indicate that p12 ( I ) may confer a proliferative advantage on HTLV-1-infected cells in the presence of suboptimal antigen stimulation and that this event may account for the clonal proliferation of infected T cells in vivo .

Together , these data indicate that <protein>p12 ( I )</protein> may confer a proliferative advantage on <cell_type>HTLV-1-infected cells</cell_type> in the presence of suboptimal antigen stimulation and that this event may account for the clonal proliferation of <cell_type>infected T cells</cell_type> in vivo .


( Blood. 2001 ; 98 : 823-829 )


Single dose intranasal administration of retinal autoantigen generates a rapid accumulation and cell activation in draining lymph node and spleen : implications for tolerance therapy .

Single dose intranasal administration of <protein>retinal autoantigen</protein> generates a rapid accumulation and cell activation in draining lymph node and spleen : implications for tolerance therapy .


BACKGROUND/AIMS : A single intranasal delivery of retinal autoantigen suppresses effectively experimental autoimmune uveoretinitis ( EAU ) .

BACKGROUND/AIMS : A single intranasal delivery of <protein>retinal autoantigen</protein> suppresses effectively experimental autoimmune uveoretinitis ( EAU ) .


To further unravel underlying mechanisms the authors wished to determine , firstly , the kinetics of antigen delivery and , secondly , the early cellular responses involved in the initial stages of nasal mucosal tolerance induction .


METHODS : Flow cytometry , cell proliferation assays , and microscopy were used to track antigen following a single , intranasal dose of Alexa-488 labelled retinal antigen .

METHODS : Flow cytometry , cell proliferation assays , and microscopy were used to track <protein>antigen</protein> following a single , intranasal dose of <protein>Alexa-488 labelled retinal antigen</protein> .


RESULTS : A rapid accumulation of antigen within both superficial cervical lymph nodes ( SCLN ) and spleen was observed after 30 minutes .

RESULTS : A rapid accumulation of <protein>antigen</protein> within both superficial cervical lymph nodes ( SCLN ) and spleen was observed after 30 minutes .


Significant proliferative responses to IRBP were elicited by 48 hours indicating that systemic priming of naive T cells to retinal antigen had occurred .

Significant proliferative responses to IRBP were elicited by 48 hours indicating that systemic priming of <cell_type>naive T cells</cell_type> to <protein>retinal antigen</protein> had occurred .


Cell activation was further confirmed by immunoprecipitation studies , which demonstrated phosphorylation of STAT4 but not STAT6 in both lymph nodes and spleen .

Cell activation was further confirmed by immunoprecipitation studies , which demonstrated phosphorylation of <protein>STAT4</protein> but not <protein>STAT6</protein> in both lymph nodes and spleen .


However , at 24 hours , STAT4 heterodimerisation with STAT 3 was only observed in spleen .

However , at 24 hours , STAT4 heterodimerisation with <protein>STAT 3</protein> was only observed in spleen .


CONCLUSIONS : The results provide novel evidence that following a single intranasal application rapid transfer of antigen occurs .

CONCLUSIONS : The results provide novel evidence that following a single intranasal application rapid transfer of <protein>antigen</protein> occurs .


Resulting T cell proliferation develops consequent to differential cell signalling in SCLN and spleen .


Further understanding of these underlying cellular mechanisms , in particular as is inferred by the results the contribution of local versus systemic tolerance induction , may assist in strategies to clinically apply mucosal tolerance therapy successfully .


Regulation of interleukin ( IL ) -18 receptor alpha chain expression on CD4 ( + ) T cells during T helper ( Th ) 1/Th2 differentiation .

Regulation of <protein>interleukin ( IL ) -18 receptor alpha chain</protein> expression on <cell_type>CD4 ( + ) T cells</cell_type> during T helper ( Th ) 1/Th2 differentiation .


Critical downregulatory role of IL-4 .

Critical downregulatory role of <protein>IL-4</protein> .


Interleukin ( IL ) -18 has been well characterized as a costimulatory factor for the induction of IL-12-mediated interferon ( IFN ) -gamma production by T helper ( Th ) 1 cells , but also can induce IL-4 production and thus facilitate the differentiation of Th2 cells .

<protein>Interleukin ( IL ) -18</protein> has been well characterized as a <protein>costimulatory factor</protein> for the induction of <protein>IL-12-mediated interferon ( IFN ) -gamma</protein> production by <cell_type>T helper ( Th ) 1 cells</cell_type> , but also can induce IL-4 production and thus facilitate the differentiation of <cell_type>Th2 cells</cell_type> .


To determine the mechanisms by which IL-18 might regulate these diametrically distinct immune responses , we have analyzed the role of cytokines in the regulation of IL-18 receptor alpha chain ( IL-18Ralpha ) expression .

To determine the mechanisms by which <protein>IL-18</protein> might regulate these diametrically distinct immune responses , we have analyzed the role of <protein>cytokines</protein> in the regulation of <protein>IL-18 receptor alpha chain</protein> ( <protein>IL-18Ralpha</protein> ) expression .


The majority of peripheral CD4 ( + ) T cells constitutively expressed the IL-18Ralpha .

The majority of <cell_type>peripheral CD4 ( + ) T cells</cell_type> constitutively expressed the <protein>IL-18Ralpha</protein> .


Upon antigen stimulation in the presence of IL-12 , marked enhancement of IL-18Ralpha expression was observed .

Upon antigen stimulation in the presence of <protein>IL-12</protein> , marked enhancement of <protein>IL-18Ralpha</protein> expression was observed .


IL-12 -mediated upregulation of IL-18Ralpha required IFN-gamma .

<protein>IL-12</protein> -mediated upregulation of <protein>IL-18Ralpha</protein> required <protein>IFN-gamma</protein> .


Activated CD4 ( + ) T cells that expressed low levels of IL-18Ralpha could produce IFN-gamma when stimulated with the combination of IL-12 and IL-18 , while CD4 ( + ) cells which expressed high levels of IL-18Ralpha could respond to IL-18 alone .

<cell_type>Activated CD4 ( + ) T cells</cell_type> that expressed low levels of <protein>IL-18Ralpha</protein> could produce <protein>IFN-gamma</protein> when stimulated with the combination of <protein>IL-12</protein> and <protein>IL-18</protein> , while <cell_type>CD4 ( + ) cells</cell_type> which expressed high levels of <protein>IL-18Ralpha</protein> could respond to <protein>IL-18</protein> alone .


In contrast , T cell stimulation in the presence of IL-4 resulted in a downregulation of IL-18Ralpha expression .

In contrast , T cell stimulation in the presence of <protein>IL-4</protein> resulted in a downregulation of <protein>IL-18Ralpha</protein> expression .


Both IL-4 ( -/ ) - and signal transducer and activator of transcription ( Stat ) 6 ( -/ ) - T cells expressed higher levels of IL-18Ralpha after TCR stimulation .

Both <cell_type>IL-4 ( -/ ) - and signal transducer and activator of transcription ( Stat ) 6 ( -/ ) - T cells</cell_type> expressed higher levels of <protein>IL-18Ralpha</protein> after TCR stimulation .


Furthermore , activated T cells from Stat6 ( -/ ) - mice produced more IFN-gamma in response to IL-18 than wild-type controls .

Furthermore , <cell_type>activated T cells</cell_type> from Stat6 ( -/ ) - mice produced more <protein>IFN-gamma</protein> in response to <protein>IL-18</protein> than wild-type controls .


Thus , positive/negative regulation of the IL-18Ralpha by the major inductive cytokines ( IL-12 and IL-4 ) determines the capacity of IL-18 to polarize an immune response .

Thus , positive/negative regulation of the <protein>IL-18Ralpha</protein> by the major inductive <protein>cytokines</protein> ( <protein>IL-12</protein> and <protein>IL-4</protein> ) determines the capacity of <protein>IL-18</protein> to polarize an immune response .


Glucocorticoid-regulated transcription factors .

<protein>Glucocorticoid-regulated transcription factors</protein> .


Glucocorticoids are the most effective antiinflammatory drugs used in the treatment of asthma .


They act by binding to a specific receptor ( GR ) that , upon activation , translocates to the nucleus and either increases ( transactivates ) or decreases ( transrepresses ) gene expression .

They act by binding to a specific receptor ( <protein>GR</protein> ) that , upon activation , translocates to the nucleus and either increases ( transactivates ) or decreases ( transrepresses ) gene expression .