The molecular mechanisms underlying the sustained nuclear translocation of NF-kappa B observed in U937 monocytic cells chronically infected with human immunodeficiency virus ( HIV ) were studied .

The molecular mechanisms underlying the sustained nuclear translocation of <protein>NF-kappa B</protein> observed in <cell_line>U937 monocytic cells</cell_line> chronically infected with human immunodeficiency virus ( HIV ) were studied .


The activity of the promoter regulating the synthesis of the p105 precursor of the NF-kappa B p50 subunit was enhanced in these cells .

The activity of the <dna>promoter</dna> regulating the synthesis of the <protein>p105 precursor</protein> of the <protein>NF-kappa B p50 subunit</protein> was enhanced in these cells .


Deletions in this promoter indicated that this upregulation was mediated through the NF-kappa B- but not the AP-1-binding motif , by bona fide p50/p65 heterodimers .

Deletions in this <dna>promoter</dna> indicated that this upregulation was mediated through the NF-kappa B- but not the <dna>AP-1-binding motif</dna> , by bona fide <protein>p50/p65 heterodimers</protein> .


Analysis of cytosolic extracts indicated that NF-kappa B levels were increased in HIV-infected cells .

Analysis of cytosolic extracts indicated that <protein>NF-kappa B</protein> levels were increased in <cell_type>HIV-infected cells</cell_type> .


In contrast to the transient NF-kappa B activation induced by phorbol ester , the permanent NF-kappa B translocation induced by HIV infection was not dependent on PKC isoenzymes alpha and beta as shown by the use of a specific inhibitor ( GF 109203X ) .

In contrast to the transient <protein>NF-kappa B</protein> activation induced by phorbol ester , the permanent <protein>NF-kappa B</protein> translocation induced by HIV infection was not dependent on <protein>PKC isoenzymes alpha and beta</protein> as shown by the use of a specific inhibitor ( GF 109203X ) .


These observations indicate that during chronic HIV infection of U937 cells , continuous NF-kappa B ( p50/p65 ) translocation results in p105 promoter upregulation with subsequent cytosolic NF-kappa B accumulation , ready for further translocation .

These observations indicate that during chronic HIV infection of <cell_line>U937 cells</cell_line> , continuous <protein>NF-kappa B</protein> ( <protein>p50/p65</protein> ) translocation results in p105 promoter upregulation with subsequent cytosolic <protein>NF-kappa B</protein> accumulation , ready for further translocation .


This HIV-mediated mechanism results in a self-perpetuating loop of NF-kappa B production .

This HIV-mediated mechanism results in a self-perpetuating loop of <protein>NF-kappa B</protein> production .


Activation of NF-kappa B by interleukin 2 in human blood monocytes .

Activation of <protein>NF-kappa B</protein> by <protein>interleukin 2</protein> in <cell_type>human blood monocytes</cell_type> .


We report here that interleukin 2 ( IL-2 ) acts on human blood monocytes by enhancing binding activity of the transcription factor NF-kappa B to its consensus sequence in the 5 ' regulatory enhancer region of the IL-2 receptor alpha chain ( p55 ) .

We report here that <protein>interleukin 2</protein> ( <protein>IL-2</protein> ) acts on <cell_type>human blood monocytes</cell_type> by enhancing binding activity of the <protein>transcription factor NF-kappa B</protein> to its consensus sequence in the 5 ' regulatory enhancer region of the <dna>IL-2 receptor alpha chain</dna> ( <protein>p55</protein> ) .


Similarly , IL-2 activates NF-kappa B in the human monocytic cell line U 937 , but not in resting human T-cells .

Similarly , <protein>IL-2</protein> activates <protein>NF-kappa B</protein> in the <cell_line>human monocytic cell line U 937</cell_line> , but not in <cell_type>resting human T-cells</cell_type> .


This effect is detectable within 15 min and peaks 1 h after exposure to IL-2 .

This effect is detectable within 15 min and peaks 1 h after exposure to <protein>IL-2</protein> .


Enhanced NF-kappa B binding activity is followed by functional activation in that inducibility of the IL-2 receptor alpha chain is mediated by enhanced NF-kappa B binding and that a heterologous promoter containing the NF-kappa B consensus sequence ( -291 to -245 ) of the IL-2 receptor alpha chain gene is activated .

Enhanced <protein>NF-kappa B</protein> binding activity is followed by functional activation in that inducibility of the <protein>IL-2 receptor alpha chain</protein> is mediated by enhanced <protein>NF-kappa B</protein> binding and that a heterologous promoter containing the <dna>NF-kappa B consensus sequence</dna> ( <dna>-291 to -245</dna> ) of the <dna>IL-2 receptor alpha chain gene</dna> is activated .


In addition , IL-2 is capable of increasing transcript levels of the p50 gene coding for the p50 subunit of the NF-kappa B transcription factor , whereas mRNA levels of the p65 NF-kappa B gene remained unchanged .

In addition , <protein>IL-2</protein> is capable of increasing transcript levels of the <protein>p50</protein> gene coding for the <protein>p50 subunit</protein> of the <protein>NF-kappa B</protein> transcription factor , whereas mRNA levels of the <protein>p65</protein> <dna>NF-kappa B gene</dna> remained unchanged .


Studies on the biological activity of triiodothyronine sulfate .


Hepatic microsomes and isolated hepatocytes in short term culture desulfate T3 sulfate ( T3SO4 ) .

<cell_type>Hepatic microsomes</cell_type> and <cell_type>isolated hepatocytes</cell_type> in short term culture desulfate T3 sulfate ( T3SO4 ) .


We , therefore , wished to determine whether T3SO4 could mimic the action of thyroid hormone in vitro .


T3SO4 had no thyromimetic effect on the activity of Ca ( 2+ ) -ATPase in human erythrocyte membranes at doses up to 10 , 000 times the maximally effective dose of T3 ( 10 ( -10 ) mol/L ) .

T3SO4 had no thyromimetic effect on the activity of <protein>Ca ( 2+ ) -ATPase</protein> in human erythrocyte membranes at doses up to 10 , 000 times the maximally effective dose of T3 ( 10 ( -10 ) mol/L ) .


In GH4C1 pituitary cells , T3SO4 failed to displace [ 125I ] T3 from nuclear receptors in intact cells or soluble preparations .

In <cell_line>GH4C1 pituitary cells</cell_line> , T3SO4 failed to displace [ 125I ] T3 from <protein>nuclear receptors</protein> in <cell_line>intact cells</cell_line> or soluble preparations .


Thus , T3SO4 was not directly thyromimetic in either an isolated human membrane system or a pituitary cell system in which nuclear receptor occupancy correlates with GH synthesis .


Thyroid hormones inhibit [ 3H ] glycosaminoglycan synthesis by cultured human dermal fibroblasts , and T3SO4 displayed about 0.5 % the activity of T3 at 72 h .

Thyroid hormones inhibit [ 3H ] glycosaminoglycan synthesis by <cell_line>cultured human dermal fibroblasts</cell_line> , and T3SO4 displayed about 0.5 % the activity of T3 at 72 h .


Human fibroblasts contained roughly the same level of microsomal p-nitrophenyl sulfatase activity as that previously observed in hepatic microsomes .

<cell_type>Human fibroblasts</cell_type> contained roughly the same level of microsomal <protein>p-nitrophenyl sulfatase</protein> activity as that previously observed in <cell_type>hepatic microsomes</cell_type> .


Propylthiouracil ( 50 mumol/L ) did not affect the action of T3SO4 , suggesting that deiodination was not important for this activity of T3SO4 .


Thus , it appears T3SO4 has no intrinsic biological activity , but , under certain circumstances , may be reactivated by desulfation .


Human T cell activation through the activation-inducer molecule/CD69 enhances the activity of transcription factor AP-1 .

Human T cell activation through the <protein>activation-inducer molecule/CD69</protein> enhances the activity of <protein>transcription factor AP-1</protein> .


The induction of the AP-1 transcription factor has been ascribed to the early events leading to T cell differentiation and activation .

The induction of the <protein>AP-1 transcription factor</protein> has been ascribed to the early events leading to T cell differentiation and activation .


We have studied the regulation of AP-1 activity in human peripheral blood T lymphocytes stimulated through the activation inducer molecule ( AIM ) / CD69 activation pathway .

We have studied the regulation of <protein>AP-1</protein> activity in <cell_type>human peripheral blood T lymphocytes</cell_type> stimulated through the activation inducer molecule ( AIM ) / <protein>CD69</protein> activation pathway .


Phorbol esters are required to induce AIM/CD69 cell-surface expression as well as for triggering the proliferation of T cells in conjunction with anti-AIM mAb .

Phorbol esters are required to induce <protein>AIM/CD69</protein> cell-surface expression as well as for triggering the proliferation of <cell_type>T cells</cell_type> in conjunction with <protein>anti-AIM mAb</protein> .


Mobility shift assays showed that addition of anti-AIM mAb to PMA-treated T lymphocytes markedly enhanced the binding activity of AP-1 to its cognate sequence , the phorbol ester response element .

Mobility shift assays showed that addition of <protein>anti-AIM mAb</protein> to <cell_type>PMA-treated T lymphocytes</cell_type> markedly enhanced the binding activity of <protein>AP-1</protein> to its cognate sequence , the <dna>phorbol ester response element</dna> .


In contrast , anti-AIM mAb did not induce any change in the binding activity of NF-kappa B , a transcription factor whose activity is also regulated by protein kinase C .

In contrast , <protein>anti-AIM mAb</protein> did not induce any change in the binding activity of <protein>NF-kappa B</protein> , a <protein>transcription factor</protein> whose activity is also regulated by <protein>protein kinase C</protein> .


The increase in AP-1 -binding activity was accompanied by the marked stimulation of the transcription of c-fos but not that of c-jun .

The increase in <protein>AP-1</protein> -binding activity was accompanied by the marked stimulation of the transcription of <protein>c-fos</protein> but not that of <protein>c-jun</protein> .


Blockade of the DNA-binding complexes with an anti-Fos mAb demonstrated a direct participation of c-Fos in the AP-1 complexes induced by anti-AIM mAb .

Blockade of the <protein>DNA-binding complexes</protein> with an <protein>anti-Fos mAb</protein> demonstrated a direct participation of <protein>c-Fos</protein> in the <protein>AP-1 complexes</protein> induced by <protein>anti-AIM mAb</protein> .


Most of the AP-1 activity could be eliminated when the anti-AIM mAb was added to the culture medium in the presence of cycloheximide , suggesting that de novo protein synthesis is crucial for the induction of AP-1 -binding activity .

Most of the <protein>AP-1</protein> activity could be eliminated when the <protein>anti-AIM mAb</protein> was added to the culture medium in the presence of cycloheximide , suggesting that de novo protein synthesis is crucial for the induction of <protein>AP-1</protein> -binding activity .


These data provide the evidence that activation of human peripheral blood T cells through the AIM activation pathway regulate the activity of AP-1 .

These data provide the evidence that activation of <cell_type>human peripheral blood T cells</cell_type> through the AIM activation pathway regulate the activity of <protein>AP-1</protein> .


Therefore , this pathway appears as a crucial step in the initiation of early T cell activation events .


Gangliosides suppress tumor necrosis factor production in human monocytes .

Gangliosides suppress <protein>tumor necrosis factor</protein> production in <cell_type>human monocytes</cell_type> .


Both normal and malignant cells contain gangliosides as important cell membrane constituents that , after being shed , may influence cells of the immune system .

Both <cell_type>normal and malignant cells</cell_type> contain gangliosides as important cell membrane constituents that , after being shed , may influence cells of the immune system .


We have studied the impact of gangliosides on the expression of TNF in blood monocytes and in the monocytic cell line Mono Mac 6 .

We have studied the impact of gangliosides on the expression of <protein>TNF</protein> in <cell_type>blood monocytes</cell_type> and in the <cell_line>monocytic cell line Mono Mac 6</cell_line> .


Although under standard culture conditions , bovine brain gangliosides ( 100 micrograms/ml ) suppressed LPS-stimulated TNF production 5-fold in PBMC and 10-fold in Mono Mac 6 cells , suppression was more efficient under serum-free conditions .

Although under standard culture conditions , bovine brain gangliosides ( 100 micrograms/ml ) suppressed LPS-stimulated <protein>TNF</protein> production 5-fold in <cell_type>PBMC</cell_type> and 10-fold in <cell_line>Mono Mac 6 cells</cell_line> , suppression was more efficient under serum-free conditions .


Looking at highly purified gangliosides , GD3 , GD1a , GM3 , GM2 , and GM1 were all effective in reducing TNF production in PBMC , and in Mono Mac 6 by factor 10 to 50 .

Looking at highly purified gangliosides , GD3 , GD1a , GM3 , GM2 , and GM1 were all effective in reducing <protein>TNF</protein> production in <cell_type>PBMC</cell_type> , and in <cell_line>Mono Mac 6</cell_line> by factor 10 to 50 .


The suppressive activity was lost in molecules , lacking the sugar moiety or the lipid moiety .


Gangliosides appear to act at an early step of activation in that TNF transcripts were reduced and the mobilization of the nuclear factor kappa B was blocked .

Gangliosides appear to act at an early step of activation in that <rna>TNF transcripts</rna> were reduced and the mobilization of the <protein>nuclear factor kappa B</protein> was blocked .


Furthermore , in time kinetics , gangliosides were effective for up to 30 min after addition of LPS , but not thereafter .


However , the expression of the CD14 Ag , a receptor molecule for LPS-LPS binding protein complexes , was unaffected by gangliosides .

However , the expression of the <protein>CD14 Ag</protein> , a <protein>receptor molecule</protein> for <protein>LPS-LPS binding protein complexes</protein> , was unaffected by gangliosides .


Finally , when using Staphylococcus aureus or platelet activating factor as a stimulus , gangliosides were able to suppress TNF production in Mono Mac 6 cells by factor 5 to 10 , as well .

Finally , when using Staphylococcus aureus or <protein>platelet activating factor</protein> as a stimulus , gangliosides were able to suppress <protein>TNF</protein> production in <cell_line>Mono Mac 6 cells</cell_line> by factor 5 to 10 , as well .


On the other hand , phorbol ester-induced production of O2- was similar in cells treated with and without gangliosides .


Taken together , our data demonstrate that TNF gene expression in monocytes induced by different types of stimuli can be blocked by gangliosides at an early step of signal transduction .

Taken together , our data demonstrate that <protein>TNF</protein> gene expression in <cell_type>monocytes</cell_type> induced by different types of stimuli can be blocked by gangliosides at an early step of signal transduction .


A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site .

A novel <protein>mitogen-inducible gene product</protein> related to <protein>p50/p105-NF-kappa B</protein> participates in transactivation through a <dna>kappa B site</dna> .


A Rel-related , mitogen-inducible , kappa B-binding protein has been cloned as an immediate-early activation gene of human peripheral blood T cells .

A <protein>Rel-related , mitogen-inducible , kappa B-binding protein</protein> has been cloned as an <dna>immediate-early activation gene</dna> of <cell_type>human peripheral blood T cells</cell_type> .


The cDNA has an open reading frame of 900 amino acids capable of encoding a 97-kDa protein .

The <dna>cDNA</dna> has an <dna>open reading frame</dna> of <dna>900 amino acids</dna> capable of encoding a <protein>97-kDa protein</protein> .


This protein is most similar to the 105-kDa precursor polypeptide of p50-NF-kappa B .

This protein is most similar to the 105-kDa precursor polypeptide of <protein>p50-NF-kappa B</protein> .


Like the 105-kDa precursor , it contains an amino-terminal Rel-related domain of about 300 amino acids and a carboxy-terminal domain containing six full cell cycle or ankyrin repeats .

Like the 105-kDa precursor , it contains an <protein>amino-terminal Rel-related domain</protein> of about 300 amino acids and a <protein>carboxy-terminal domain</protein> containing six <protein>full cell cycle</protein> or <protein>ankyrin repeats</protein> .


In vitro-translated proteins , truncated downstream of the Rel domain and excluding the repeats , bind kappa B sites .

In <protein>vitro-translated proteins</protein> , truncated downstream of the <dna>Rel domain</dna> and excluding the repeats , bind <dna>kappa B sites</dna> .


We refer to the kappa B-binding , truncated protein as p50B by analogy with p50-NF-kappa B and to the full-length protein as p97 .

We refer to the <protein>kappa B-binding , truncated protein</protein> as <protein>p50B</protein> by analogy with <protein>p50-NF-kappa B</protein> and to the full-length protein as <protein>p97</protein> .


p50B is able to form heteromeric kappa B-binding complexes with RelB , as well as with p65 and p50 , the two subunits of NF-kappa B .

<protein>p50B</protein> is able to form <protein>heteromeric kappa B-binding complexes</protein> with <protein>RelB</protein> , as well as with <protein>p65</protein> and <protein>p50</protein> , the two subunits of <protein>NF-kappa B</protein> .


Transient-transfection experiments in embryonal carcinoma cells demonstrate a functional cooperation between p50B and RelB or p65 in transactivation of a reporter plasmid dependent on a kappa B site .

Transient-transfection experiments in <cell_line>embryonal carcinoma cells</cell_line> demonstrate a functional cooperation between <protein>p50B</protein> and <protein>RelB</protein> or <protein>p65</protein> in transactivation of a <dna>reporter plasmid</dna> dependent on a <dna>kappa B site</dna> .


The data imply the existence of a complex family of NF-kappa B-like transcription factors .

The data imply the existence of a complex family of <protein>NF-kappa B-like transcription factors</protein> .


Surrogate thyroglobulin receptors and T cell proliferation in Hashimoto 's thyroiditis .

Surrogate <protein>thyroglobulin receptors</protein> and T cell proliferation in Hashimoto 's thyroiditis .


Immunoglobulin molecules on the surface of a B lymphocyte are the endogenous `` receptors '' to which specific antigens bind .

<protein>Immunoglobulin molecules</protein> on the surface of a <cell_type>B lymphocyte</cell_type> are the endogenous `` receptors '' to which specific antigens bind .


Studies in mice have shown that a monoclonal antibody , conjugated with palmitate to provide a lipid tail , can be inserted into the cell membrane to provide a `` surrogate '' antigen receptor .

Studies in mice have shown that a <protein>monoclonal antibody</protein> , conjugated with palmitate to provide a lipid tail , can be inserted into the cell membrane to provide a `` surrogate '' antigen receptor .


We have investigated whether a palmitate conjugate of a human monoclonal antibody specific for thyroglobulin ( TG ) could function as a surrogate TG receptor on blood mononuclear cells separated into fractions enriched for T cells or depleted of T cells ( non-T cells ) .

We have investigated whether a <protein>palmitate conjugate</protein> of a <protein>human monoclonal antibody</protein> specific for <protein>thyroglobulin</protein> ( <protein>TG</protein> ) could function as a <protein>surrogate TG receptor</protein> on <cell_type>blood mononuclear cells</cell_type> separated into fractions enriched for <cell_type>T cells</cell_type> or depleted of <cell_type>T cells</cell_type> ( <cell_type>non-T cells</cell_type> ) .


Using flow cytometry , we detected surrogate TG receptors on non-T ( but not on T ) cells from 11 of 11 individuals studied ( 5 Hashimoto patients and 6 control donors ) .

Using flow cytometry , we detected <protein>surrogate TG receptors</protein> on <cell_type>non-T ( but not on T ) cells</cell_type> from 11 of 11 individuals studied ( 5 Hashimoto patients and 6 control donors ) .


In contrast , endogenous TG receptors could only be detected on non-T cells from 1 of 3 Hashimoto patients and from 0 of 4 control donors .

In contrast , <protein>endogenous TG receptors</protein> could only be detected on <cell_type>non-T cells</cell_type> from 1 of 3 Hashimoto patients and from 0 of 4 control donors .


Because of the efficient binding of TG by surrogate receptors on non-T cells , we assessed the ability of such cells to present TG to T cells .

Because of the efficient binding of <protein>TG</protein> by <protein>surrogate receptors</protein> on <cell_type>non-T cells</cell_type> , we assessed the ability of such cells to present <protein>TG</protein> to <cell_type>T cells</cell_type> .


Proliferation in response to TG was observed in T cells from only 1 of 5 Hashimoto patients .

Proliferation in response to <protein>TG</protein> was observed in <cell_type>T cells</cell_type> from only 1 of 5 Hashimoto patients .


This low frequency of response was no different from that previously detected using cultures of T cells and autologous dendritic cells .

This low frequency of response was no different from that previously detected using cultures of <cell_type>T cells</cell_type> and <cell_type>autologous dendritic cells</cell_type> .


Therefore , the successful generation of surrogate receptors on non-T cells is not associated with more efficient TG presentation of T cells .

Therefore , the successful generation of <protein>surrogate receptors</protein> on <cell_type>non-T cells</cell_type> is not associated with more efficient <protein>TG</protein> presentation of <cell_type>T cells</cell_type> .


Furthermore , the significance of the present study is that the T cells , not the antigen-presenting cells , are likely to be the limiting element in the T cell proliferative response to TG and other thyroid autoantigens .

Furthermore , the significance of the present study is that the <cell_type>T cells</cell_type> , not the <cell_type>antigen-presenting cells</cell_type> , are likely to be the limiting element in the T cell proliferative response to <protein>TG</protein> and other <protein>thyroid autoantigens</protein> .


Targeted degradation of c-Fos , but not v-Fos , by a phosphorylation-dependent signal on c-Jun .

Targeted degradation of <protein>c-Fos</protein> , but not <protein>v-Fos</protein> , by a <protein>phosphorylation-dependent signal</protein> on <protein>c-Jun</protein> .


The proto-oncogene products c-Fos and c-Jun heterodimerize through their leucine zippers to form the AP-1 transcription factor .

The <protein>proto-oncogene products</protein> <protein>c-Fos</protein> and <protein>c-Jun</protein> heterodimerize through their <protein>leucine zippers</protein> to form the <protein>AP-1 transcription factor</protein> .


The transcriptional activity of the heterodimer is regulated by signal-dependent phosphorylation and dephosphorylation events .


The stability of c-Fos was found to also be controlled by intracellular signal transduction .

The stability of <protein>c-Fos</protein> was found to also be controlled by intracellular signal transduction .


In transient expression and in vitro degradation experiments , the stability of c-Fos was decreased when the protein was dimerized with phosphorylated c-Jun .

In transient expression and in vitro degradation experiments , the stability of <protein>c-Fos</protein> was decreased when the protein was dimerized with <protein>phosphorylated c-Jun</protein> .


c-Jun protein isolated from phorbol ester-induced cells did not target c-Fos for degradation , which suggests that c-Fos is transiently stabilized after stimulation of cell growth .

<protein>c-Jun</protein> protein isolated from <cell_line>phorbol ester-induced cells</cell_line> did not target <protein>c-Fos</protein> for degradation , which suggests that <protein>c-Fos</protein> is transiently stabilized after stimulation of cell growth .


v-Fos protein , the retroviral counterpart of c-Fos , was not susceptible to degradation targeted by c-Jun .

<protein>v-Fos protein</protein> , the retroviral counterpart of <protein>c-Fos</protein> , was not susceptible to degradation targeted by <protein>c-Jun</protein> .


The regulation of the human tumor necrosis factor alpha promoter region in macrophage , T cell , and B cell lines .

The regulation of the <dna>human tumor necrosis factor alpha promoter region</dna> in <cell_line>macrophage</cell_line> , <cell_line>T cell</cell_line> , and <cell_line>B cell lines</cell_line> .


The 1311-base pair human tumor necrosis factor ( TNF ) alpha promoter region was fused to the luciferase ( Luc ) reporter gene and studied in a transient transfection system in three TNF producing cell lines , the U937 macrophage cell line , the MLA 144 T cell line , and the 729-6 B cell line .

The <dna>1311-base pair human tumor necrosis factor ( TNF ) alpha promoter region</dna> was fused to the <dna>luciferase ( Luc ) reporter gene</dna> and studied in a transient transfection system in three <cell_line>TNF producing cell lines</cell_line> , the <cell_line>U937 macrophage cell line</cell_line> , the <cell_line>MLA 144 T cell line</cell_line> , and the <cell_line>729-6 B cell line</cell_line> .


This full length promoter construct can be induced by phorbol 13-myristate acetate ( PMA ) in each of these cell types .


Analysis of a series of 5'-truncations showed several peaks of basal and PMA induced activity suggesting the presence of several positive and negative regulatory elements .

Analysis of a series of <dna>5'-truncations</dna> showed several peaks of basal and PMA induced activity suggesting the presence of several <dna>positive</dna> and negative regulatory elements .


A PMA responsive element was localized to a region between -95 and -36 bp relative to the transcription start site .

A <dna>PMA responsive element</dna> was localized to a region between <dna>-95 and -36 bp</dna> relative to the <dna>transcription start site</dna> .


Within this region , single AP-2- and AP-1- like consensus sequences were noted .

Within this region , single <dna>AP-2- and AP-1- like consensus sequences</dna> were noted .


These AP-2 and AP-1 sites were each modified with a double point mutation .

These <dna>AP-2</dna> and <dna>AP-1 sites</dna> were each modified with a double point mutation .


A modest ( 20-50 % ) reduction in TNF promoter activity was observed with the AP-2 site mutation .

A modest ( 20-50 % ) reduction in <dna>TNF promoter</dna> activity was observed with the <dna>AP-2 site mutation</dna> .


However , mutation of the AP-1 site markedly diminished both the basal and PMA-activated promoter activity .

However , mutation of the <dna>AP-1 site</dna> markedly diminished both the basal and PMA-activated promoter activity .


Also co-transfections of the wild-type promoter construct with an AP-1/c-jun expression vector resulted in augmented basal and PMA-induced promoter activity .

Also co-transfections of the <dna>wild-type promoter construct</dna> with an <dna>AP-1/c-jun expression vector</dna> resulted in augmented basal and PMA-induced promoter activity .


Stable expression of transdominant Rev protein in human T cells inhibits human immunodeficiency virus replication .

Stable expression of <protein>transdominant Rev protein</protein> in <cell_type>human T cells</cell_type> inhibits human immunodeficiency virus replication .


The human immunodeficiency virus ( HIV ) Rev protein is essential for viral structural protein expression ( Gag , Pol , and Env ) and , hence , for viral replication .

The human immunodeficiency virus ( HIV ) <protein>Rev protein</protein> is essential for viral structural protein expression ( <protein>Gag</protein> , <protein>Pol</protein> , and <protein>Env</protein> ) and , hence , for viral replication .


In transient transfection assays , mutant forms of Rev have been identified that inhibit wild-type Rev activity and therefore suppress viral replication .

In transient transfection assays , mutant forms of <protein>Rev</protein> have been identified that inhibit wild-type <protein>Rev</protein> activity and therefore suppress viral replication .


To determine whether such transdominant Rev proteins could provide long-term protection against HIV infection without affecting T cell function , T leukemia cell lines were stably transduced with a retroviral vector encoding a transdominant mutant of the Rev protein , M10 .

To determine whether such <protein>transdominant Rev proteins</protein> could provide long-term protection against HIV infection without affecting T cell function , <cell_line>T leukemia cell lines</cell_line> were stably transduced with a <dna>retroviral vector</dna> encoding a transdominant mutant of the <protein>Rev protein</protein> , <protein>M10</protein> .


While all the M10-expressing cell lines remained infectable by HIV-1 , these same cells failed to support a productive replication cycle when infected with a cloned isolate of HIV-1 .

While all the <cell_line>M10-expressing cell lines</cell_line> remained infectable by HIV-1 , these same cells failed to support a productive replication cycle when infected with a cloned isolate of HIV-1 .


In addition , two out of three M10-expressing CEM clones were also resistant to highly productive infection by a heterogeneous HIV-1 pool .

In addition , two out of three <cell_line>M10-expressing CEM clones</cell_line> were also resistant to highly productive infection by a heterogeneous HIV-1 pool .


Expression of M10 did not affect induction of HIV transcription mediated by the kappa B regulatory element or Tat .

Expression of <protein>M10</protein> did not affect induction of HIV transcription mediated by the <dna>kappa B regulatory element</dna> or <protein>Tat</protein> .


Importantly , constitutive expression of Rev M10 did not alter the secretion of interleukin 2 in response to mitogen stimulation of EL-4 and Jurkat cells .

Importantly , constitutive expression of <protein>Rev M10</protein> did not alter the secretion of <protein>interleukin 2</protein> in response to mitogen stimulation of <cell_line>EL-4</cell_line> and <cell_line>Jurkat cells</cell_line> .


The inhibition of HIV infection in cells stably expressing a transdominant Rev protein , in the absence of any deleterious effect on T cell function , suggests that such a strategy could provide a therapeutic effect in the T lymphocytes of acquired immunodeficiency syndrome patients .

The inhibition of HIV infection in cells stably expressing a <protein>transdominant Rev protein</protein> , in the absence of any deleterious effect on T cell function , suggests that such a strategy could provide a therapeutic effect in the <cell_type>T lymphocytes</cell_type> of acquired immunodeficiency syndrome patients .


Simple derivation of TFIID-dependent RNA polymerase II transcription systems from Schizosaccharomyces pombe and other organisms , and factors required for transcriptional activation .

Simple derivation of TFIID-dependent <protein>RNA polymerase II</protein> transcription systems from Schizosaccharomyces pombe and other organisms , and factors required for transcriptional activation .


Resolution of whole cell extract through two chromatographic steps yields a single protein fraction requiring only the addition of TFIID for the initiation of transcription at RNA polymerase II promoters .

Resolution of whole cell extract through two chromatographic steps yields a single protein fraction requiring only the addition of <protein>TFIID</protein> for the initiation of transcription at <dna>RNA polymerase II promoters</dna> .


This approach allows the convenient generation of RNA polymerase II transcription systems from Saccharomyces cerevisiae , human lymphocytes , and Schizosaccharomyces pombe .

This approach allows the convenient generation of <protein>RNA polymerase II</protein> transcription systems from Saccharomyces cerevisiae , <cell_type>human lymphocytes</cell_type> , and Schizosaccharomyces pombe .


TFIIDs from all three organisms are interchangeable among all three systems .

<protein>TFIIDs</protein> from all three organisms are interchangeable among all three systems .


The S. cerevisiae and Sch. pombe systems support effects of acidic activator proteins , provided a further protein fraction from S. cerevisiae is supplied .

The S. cerevisiae and Sch. pombe systems support effects of <protein>acidic activator proteins</protein> , provided a further protein fraction from S. cerevisiae is supplied .


This further fraction is distinct from the mediator of transcriptional activation described previously and represents a second component in addition to general initiation factors that may facilitate a response to acidic activators .

This further fraction is distinct from the mediator of transcriptional activation described previously and represents a second component in addition to <protein>general initiation factors</protein> that may facilitate a response to <protein>acidic activators</protein> .


Regulation of c-jun expression during induction of monocytic differentiation by okadaic acid .

Regulation of <dna>c-jun</dna> expression during induction of monocytic differentiation by okadaic acid .


The present work has examined the effects of okadaic acid , an inhibitor of type 1 and 2A protein phosphatases , on the regulation of c-jun expression during monocytic differentiation of U-937 leukemia cells .

The present work has examined the effects of okadaic acid , an inhibitor of <protein>type 1 and 2A protein phosphatases</protein> , on the regulation of <dna>c-jun</dna> expression during monocytic differentiation of <cell_line>U-937 leukemia cells</cell_line> .


The results demonstrate that okadaic acid treatment is associated with induction of a differentiated monocyte phenotype characterized by : ( a ) growth arrest ; ( b ) increases in Mac-1 cell surface antigen expression ; ( c ) down-regulation of c-myc transcripts ; and ( d ) induction of tumor necrosis factor gene expression .

The results demonstrate that okadaic acid treatment is associated with induction of a differentiated monocyte phenotype characterized by : ( a ) growth arrest ; ( b ) increases in <protein>Mac-1 cell surface antigen</protein> expression ; ( c ) down-regulation of <protein>c-myc transcripts</protein> ; and ( d ) induction of <dna>tumor necrosis factor gene</dna> expression .


This induction of monocytic differentiation was associated with transient increases in c-jun mRNA levels , which were maximal at 6 h .

This induction of monocytic differentiation was associated with transient increases in <rna>c-jun mRNA</rna> levels , which were maximal at 6 h .


Similar effects were obtained for the c-fos gene .

Similar effects were obtained for the <dna>c-fos gene</dna> .


Run-on analysis demonstrated detectable levels of c-jun transcription in U-937 cells and that this rate is increased approximately 40-fold following okadaic acid exposure .

Run-on analysis demonstrated detectable levels of <dna>c-jun</dna> transcription in <cell_line>U-937 cells</cell_line> and that this rate is increased approximately 40-fold following okadaic acid exposure .


c-jun mRNA levels were superinduced in cells treated with both okadaic acid and cycloheximide , whereas inhibition of protein synthesis had little , if any , effect on okadaic acid-induced c-jun transcription .

<rna>c-jun mRNA</rna> levels were superinduced in cells treated with both okadaic acid and cycloheximide , whereas inhibition of protein synthesis had little , if any , effect on okadaic acid-induced <dna>c-jun</dna> transcription .


The half-life of c-jun mRNA was similar ( 45-50 min ) in both untreated and okadaic acid-induced cells .

The half-life of <rna>c-jun mRNA</rna> was similar ( 45-50 min ) in both untreated and <cell_line>okadaic acid-induced cells</cell_line> .


In contrast , treatment with both okadaic acid and cycloheximide was associated with stabilization ( t 1/2 = 90 min ) of c-jun transcripts .

In contrast , treatment with both okadaic acid and cycloheximide was associated with stabilization ( t 1/2 = 90 min ) of <protein>c-jun transcripts</protein> .


Taken together , these findings indicate that the induction of c-jun transcription by okadaic acid is controlled primarily by a transcriptional mechanism .

Taken together , these findings indicate that the induction of <dna>c-jun</dna> transcription by okadaic acid is controlled primarily by a transcriptional mechanism .


Since previous studies have demonstrated that the c-jun gene is autoinduced by Jun/AP-1 , we also studied transcription of c-jun promoter ( positions -132/+170 ) -reporter gene constructs with and without a mutated AP-1 element .

Since previous studies have demonstrated that the <dna>c-jun gene</dna> is autoinduced by <protein>Jun/AP-1</protein> , we also studied transcription of <dna>c-jun promoter ( positions -132/+170 ) -reporter gene constructs</dna> with and without a mutated <dna>AP-1 element</dna> .


( ABSTRACT TRUNCATED AT 250 WORDS )


Mitogen stimulation of T-cells increases c-Fos and c-Jun protein levels , AP-1 binding and AP-1 transcriptional activity .

Mitogen stimulation of T-cells increases <protein>c-Fos</protein> and <protein>c-Jun</protein> protein levels , AP-1 binding and AP-1 transcriptional activity .


We have analysed the effect of mitogenic lectins on c-Fos and c-Jun protein levels as well as on activator protein-1 ( AP-1 ) binding and enhancer activity in Jurkat T-cells .

We have analysed the effect of mitogenic lectins on <protein>c-Fos</protein> and <protein>c-Jun</protein> protein levels as well as on activator protein-1 ( AP-1 ) binding and enhancer activity in Jurkat T-cells .


Both c-Fos and c-Jun protein levels were increased after Con A and PHA stimulation .

Both <protein>c-Fos</protein> and <protein>c-Jun</protein> protein levels were increased after Con A and PHA stimulation .


Since T-cell stimulation increases both intracellular Ca2+ and cAMP levels and activates protein kinase C ( PKC ) , the possible involvement of these intracellular messengers in c-Fos and c-Jun induction was tested .

Since T-cell stimulation increases both intracellular Ca2+ and cAMP levels and activates protein kinase C ( PKC ) , the possible involvement of these intracellular messengers in <protein>c-Fos</protein> and <protein>c-Jun</protein> induction was tested .


PMA , which directly activates PKC , mimicked the effect of the lectins on c-Fos and c-Jun , but elevation of either intracellular Ca2+ or cAMP levels had little or no effect .

PMA , which directly activates PKC , mimicked the effect of the lectins on c-Fos and <protein>c-Jun</protein> , but elevation of either intracellular Ca2+ or cAMP levels had little or no effect .


The mitogen-induced increase of c-Fos and c-Jun immunoreactivity was inhibited by H-7 , a kinase inhibitor with relatively high specificity for PKC , and less efficiently by H-8 , a structurally related kinase inhibitor less active on PKC , but more active on cyclic nucleotide-dependent kinases .

The mitogen-induced increase of <protein>c-Fos</protein> and <protein>c-Jun</protein> immunoreactivity was inhibited by H-7 , a kinase inhibitor with relatively high specificity for PKC , and less efficiently by H-8 , a structurally related kinase inhibitor less active on PKC , but more active on cyclic nucleotide-dependent kinases .


Con A stimulation was found to increase both binding of AP-1 to the AP-1 consensus sequence , TRE , and AP-1 enhancer activity , in Jurkat cells .

Con A stimulation was found to increase both binding of AP-1 to the AP-1 consensus sequence , TRE , and AP-1 enhancer activity , in <cell_line>Jurkat cells</cell_line> .


PMA was also found to increase the AP-1 enhancer activity , whereas elevation of Ca2+ or cAMP had only minor effects .


We conclude that stimulation with mitogenic lectins is sufficient to increase both c-Fos and c-Jun protein levels , AP-1 binding and AP-1 enhancer activity in Jurkat cells and that they act via mechanisms that could involve the activation of PKC .

We conclude that stimulation with mitogenic lectins is sufficient to increase both <protein>c-Fos</protein> and <protein>c-Jun</protein> protein levels , AP-1 binding and AP-1 enhancer activity in <cell_line>Jurkat cells</cell_line> and that they act via mechanisms that could involve the activation of PKC .


An 11-base-pair DNA sequence motif apparently unique to the human interleukin 4 gene confers responsiveness to T-cell activation signals .

An 11-base-pair DNA sequence motif apparently unique to the <dna>human interleukin 4 gene</dna> confers responsiveness to T-cell activation signals .


We have identified a DNA segment that confers responsiveness to antigen stimulation signals on the human interleukin ( IL ) 4 gene in Jurkat cells .

We have identified a <dna>DNA segment</dna> that confers responsiveness to antigen stimulation signals on the <dna>human interleukin ( IL ) 4 gene</dna> in <cell_line>Jurkat cells</cell_line> .


The human IL-4 gene , of 10 kilobases , is composed of four exons and three introns .

The <dna>human IL-4 gene</dna> , of 10 kilobases , is composed of four <dna>exons</dna> and three <dna>introns</dna> .


A cis-acting element ( P sequence ) resides in the 5 ' upstream region ; no additional DNA segments with enhancer activity were identified in the human IL-4 gene .

A <dna>cis-acting element</dna> ( <dna>P sequence</dna> ) resides in the <dna>5 ' upstream region</dna> ; no additional <dna>DNA segments</dna> with enhancer activity were identified in the <dna>human IL-4 gene</dna> .


For further mapping purposes , a fusion promoter was constructed with the granulocyte/macrophage colony-stimulating factor basic promoter containing 60 base pairs of sequence upstream from the cap site of the mouse granulocyte/macrophage colony-stimulating factor gene and various lengths of the 5 ' upstream sequence of the IL-4 gene .

For further mapping purposes , a <dna>fusion promoter</dna> was constructed with the <dna>granulocyte/macrophage colony-stimulating factor basic promoter</dna> containing <dna>60 base pairs of sequence</dna> upstream from the <dna>cap site</dna> of the <dna>mouse granulocyte/macrophage colony-stimulating factor gene</dna> and various lengths of the <dna>5 ' upstream sequence</dna> of the <dna>IL-4 gene</dna> .


The P sequence was located between positions -79 and -69 relative to the transcription start site of the human IL-4 gene , and this location was confirmed by base-substitution mutations .

The <dna>P sequence</dna> was located between positions -79 and -69 relative to the <dna>transcription start site</dna> of the <dna>human IL-4 gene</dna> , and this location was confirmed by base-substitution mutations .


The plasmids carrying multiple copies of the P sequence showed higher responsiveness to the stimulation .

The plasmids carrying multiple copies of the <dna>P sequence</dna> showed higher responsiveness to the stimulation .


The binding protein ( s ) that recognize the P sequence of the IL-4 gene were identified by DNA-mobility-shift assays .

The <protein>binding protein</protein> ( s ) that recognize the <dna>P sequence</dna> of the <dna>IL-4 gene</dna> were identified by DNA-mobility-shift assays .


The binding of NF ( P ) ( a DNA binding protein that specifically recognizes the P sequence ) to the P sequence was abolished when oligonucleotides carrying base substitutions were used , indicating that the NF ( P ) interaction is sequence-specific and that binding specificity of the protein paralleled the sequence requirements for IL-4 expression in vivo .

The binding of <protein>NF ( P )</protein> ( a <protein>DNA binding protein</protein> that specifically recognizes the <dna>P sequence</dna> ) to the <dna>P sequence</dna> was abolished when oligonucleotides carrying base substitutions were used , indicating that the <protein>NF ( P )</protein> interaction is sequence-specific and that binding specificity of the protein paralleled the sequence requirements for <protein>IL-4</protein> expression in vivo .


The P sequence does not share homology with the 5 ' upstream sequence of the IL-2 gene , even though surrounding sequences of the IL-4 gene share high homology with the IL-2 gene .

The <dna>P sequence</dna> does not share homology with the <dna>5 ' upstream sequence</dna> of the <dna>IL-2 gene</dna> , even though surrounding sequences of the <dna>IL-4 gene</dna> share high homology with the <dna>IL-2 gene</dna> .


We conclude that a different set of proteins recognize IL-2 and IL-4 genes .

We conclude that a different set of <protein>proteins</protein> recognize <dna>IL-2 and IL-4 genes</dna> .


Leukotriene B4 stimulates c-fos and c-jun gene transcription and AP-1 binding activity in human monocytes .

Leukotriene B4 stimulates c-fos and c-jun gene transcription and <protein>AP-1</protein> binding activity in <cell_type>human monocytes</cell_type> .


We have examined the effect of leukotriene B4 ( LTB4 ) , a potent lipid proinflammatory mediator , on the expression of the proto-oncogenes c-jun and c-fos .

We have examined the effect of leukotriene B4 ( LTB4 ) , a potent lipid <protein>proinflammatory mediator</protein> , on the expression of the <dna>proto-oncogenes c-jun and c-fos</dna> .


In addition , we looked at the modulation of nuclear factors binding specifically to the AP-1 element after LTB4 stimulation .

In addition , we looked at the modulation of <protein>nuclear factors</protein> binding specifically to the <dna>AP-1 element</dna> after LTB4 stimulation .


LTB4 increased the expression of the c-fos gene in a time- and concentration-dependent manner .

LTB4 increased the expression of the <dna>c-fos gene</dna> in a time- and concentration-dependent manner .


The c-jun mRNA , which is constitutively expressed in human peripheral-blood monocytes at relatively high levels , was also slightly augmented by LTB4 , although to a much lower extent than c-fos .

The <rna>c-jun mRNA</rna> , which is constitutively expressed in <cell_type>human peripheral-blood monocytes</cell_type> at relatively high levels , was also slightly augmented by LTB4 , although to a much lower extent than <dna>c-fos</dna> .


The kinetics of expression of the two genes were also slightly different , with c-fos mRNA reaching a peak at 15 min after stimulation and c-jun at 30 min .

The kinetics of expression of the two genes were also slightly different , with <rna>c-fos mRNA</rna> reaching a peak at 15 min after stimulation and <dna>c-jun</dna> at 30 min .


Both messages rapidly declined thereafter .


Stability of the c-fos and c-jun mRNA was not affected by LTB4 , as assessed after actinomycin D treatment .

Stability of the <dna>c-fos</dna> and <rna>c-jun mRNA</rna> was not affected by LTB4 , as assessed after actinomycin D treatment .


Nuclear transcription studies in vitro showed that LTB4 increased the transcription of the c-fos gene 7-fold and the c-jun gene 1.4-fold .

Nuclear transcription studies in vitro showed that LTB4 increased the transcription of the <dna>c-fos gene</dna> 7-fold and the <dna>c-jun gene</dna> 1.4-fold .


Resting monocytes contained nuclear factors binding to the AP-1 element , but stimulation of monocytes with LTB4 induced greater AP-1 -binding activity of nuclear proteins .

<cell_type>Resting monocytes</cell_type> contained <protein>nuclear factors</protein> binding to the <dna>AP-1 element</dna> , but stimulation of <cell_type>monocytes</cell_type> with LTB4 induced greater <protein>AP-1</protein> -binding activity of <protein>nuclear proteins</protein> .


These results indicate that LTB4 may regulate the production of different cytokines by modulating the yield and/or the function of transcription factors such as AP-1 -binding proto-oncogene products .

These results indicate that LTB4 may regulate the production of different <protein>cytokines</protein> by modulating the yield and/or the function of <protein>transcription factors</protein> such as <protein>AP-1</protein> -binding <protein>proto-oncogene products</protein> .


Modulation of normal erythroid differentiation by the endogenous thyroid hormone and retinoic acid receptors : a possible target for v-erbA oncogene action .

Modulation of normal erythroid differentiation by the endogenous thyroid hormone and <protein>retinoic acid receptors</protein> : a possible target for <dna>v-erbA oncogene</dna> action .


The v-erbA oncogene , a mutated version of the thyroid hormone receptor alpha ( c-erbA/TR-alpha ) , inhibits erythroid differentiation and constitutively represses transcription of certain erythrocyte genes , suggesting a normal function of the proto-oncogene c-erbA in erythropoiesis .

The <dna>v-erbA oncogene</dna> , a mutated version of the <protein>thyroid hormone receptor alpha</protein> ( <protein>c-erbA/TR-alpha</protein> ) , inhibits erythroid differentiation and constitutively represses transcription of certain <dna>erythrocyte genes</dna> , suggesting a normal function of the <dna>proto-oncogene c-erbA</dna> in erythropoiesis .


Here we demonstrate that the endogenous thyroid hormone receptor alpha ( c-erbA/TR-alpha ) and the closely related retinoic acid receptor alpha ( RAR-alpha ) play a role in the regulation of normal erythroid differentiation .

Here we demonstrate that the endogenous <protein>thyroid hormone receptor alpha</protein> ( <protein>c-erbA/TR-alpha</protein> ) and the closely related <protein>retinoic acid receptor alpha</protein> ( <protein>RAR-alpha</protein> ) play a role in the regulation of normal erythroid differentiation .


Retinoic acid ( RA ) distinctly modulated the erythroid differentiation program of normal erythroid progenitors and erythroblasts reversibly transformed by a conditional tyrosine kinase oncogene .

Retinoic acid ( RA ) distinctly modulated the erythroid differentiation program of <cell_type>normal erythroid progenitors</cell_type> and erythroblasts reversibly transformed by a conditional <dna>tyrosine kinase oncogene</dna> .


When added pulsewise to immature cells , differentiation was accelerated while more mature cells underwent premature cell death .

When added pulsewise to <cell_type>immature cells</cell_type> , differentiation was accelerated while more <cell_type>mature cells</cell_type> underwent premature cell death .


Thyroid hormone ( T3 ) alone caused similar but weaker effects .


Interestingly , T3 strongly enhanced the action of RA , suggesting cooperative action of the two receptors in modulating erythroid differentiation .


Expression of the human RAR-alpha in receptor-negative erythroblasts conferred RA-induced regulation of differentiation to the otherwise unresponsive cells , thus showing that the RAR-alpha is essential for the RA effect .

Expression of the <protein>human RAR-alpha</protein> in <cell_line>receptor-negative erythroblasts</cell_line> conferred RA-induced regulation of differentiation to the otherwise <cell_type>unresponsive cells</cell_type> , thus showing that the <protein>RAR-alpha</protein> is essential for the RA effect .


Likewise , enhanced expression of exogenous c-erbA/TR-alpha in erythroblasts rendered them susceptible to modulation of differentiation by T3 , suggesting a similar function of both receptors .

Likewise , enhanced expression of <protein>exogenous c-erbA/TR-alpha</protein> in <cell_type>erythroblasts</cell_type> rendered them susceptible to modulation of differentiation by T3 , suggesting a similar function of both receptors .


Activation of lymphokine genes in T cells : role of cis-acting DNA elements that respond to T cell activation signals .

Activation of <dna>lymphokine genes</dna> in <cell_type>T cells</cell_type> : role of <dna>cis-acting DNA elements</dna> that respond to T cell activation signals .


Activation of T cells is initiated by the recognition of antigen on antigen presenting cells to exert the effector functions in immune and inflammatory responses .

Activation of <cell_type>T cells</cell_type> is initiated by the recognition of antigen on <cell_type>antigen presenting cells</cell_type> to exert the effector functions in immune and inflammatory responses .


Two types of helper T cell ( Th ) clones ( Th1 and Th2 ) are defined on the basis of different patterns of cytokine ( lymphokine ) secretion .

Two types of <cell_line>helper T cell ( Th ) clones</cell_line> ( <cell_line>Th1</cell_line> and <cell_line>Th2</cell_line> ) are defined on the basis of different patterns of <protein>cytokine</protein> ( <protein>lymphokine</protein> ) secretion .


They determine the outcome of an antigenic response toward humoral or cell-mediated immunity .


Although lymphokine genes are coordinately regulated upon antigen stimulation , they are regulated by the mechanisms common to all as well as those which are unique to each gene .

Although <dna>lymphokine genes</dna> are coordinately regulated upon antigen stimulation , they are regulated by the mechanisms common to all as well as those which are unique to each gene .


For most lymphokine genes , a combination of phorbol esters ( phorbol 12-myristate 13 acetate , PMA ) and calcium ionophores ( A23187 ) is required for their maximal induction .

For most <dna>lymphokine genes</dna> , a combination of phorbol esters ( phorbol 12-myristate 13 acetate , PMA ) and calcium ionophores ( A23187 ) is required for their maximal induction .


Yet phorbol ester alone or calcium ionophore alone produce several lymphokines .

Yet phorbol ester alone or calcium ionophore alone produce several <protein>lymphokines</protein> .


The production of the granulocyte-macrophage colony stimulating factor ( GM-CSF ) is completely dependent on the two signals .

The production of the <protein>granulocyte-macrophage colony stimulating factor</protein> ( <protein>GM-CSF</protein> ) is completely dependent on the two signals .


We have previously found a cis-acting region spanning the GM-CSF promoter region ( positions -95 to +27 ) that confers inducibility to reporter genes in transient transfection assays .

We have previously found a <dna>cis-acting region</dna> spanning the <dna>GM-CSF promoter region</dna> ( positions -95 to +27 ) that confers inducibility to <dna>reporter genes</dna> in transient transfection assays .


Further analysis identified three elements required for efficient induction , referred to as GM2 , GC-box and conserved lymphokine element ( CLE0 ) .

Further analysis identified three elements required for efficient induction , referred to as <dna>GM2</dna> , <dna>GC-box</dna> and <dna>conserved lymphokine element</dna> ( <dna>CLE0</dna> ) .


GM2 defines a binding site for protein ( s ) whose binding is inducible by PMA .

<dna>GM2</dna> defines a <dna>binding site</dna> for protein ( s ) whose binding is inducible by PMA .


One protein , NF-GM2 is similar to the transcription factor NF-kB .

One protein , <protein>NF-GM2</protein> is similar to the <protein>transcription factor</protein> <protein>NF-kB</protein> .


GC-box is a binding site for constitutively bound proteins .

<dna>GC-box</dna> is a <dna>binding site</dna> for <protein>constitutively bound proteins</protein> .


CLEO defines a binding site for protein ( s ) whose optimum binding is stimulated by PMA and A23187 .

CLEO defines a <dna>binding site</dna> for protein ( s ) whose optimum binding is stimulated by PMA and A23187 .


Viral trans-activators such as Tax ( human T cell leukemia virus-1 , HTLV-1 ) and E2 ( bovine papilloma virus , BPV ) proteins are other agents which activate lymphokine gene expression by bypassing T cell receptor ( TCR ) mediated signaling .

<protein>Viral trans-activators</protein> such as <protein>Tax</protein> ( human T cell leukemia virus-1 , HTLV-1 ) and <protein>E2</protein> ( bovine papilloma virus , BPV ) proteins are other agents which activate <dna>lymphokine gene</dna> expression by bypassing <protein>T cell receptor</protein> ( <protein>TCR</protein> ) mediated signaling .


The trans-activation domain of E2 and Tax is interchangeable although they have no obvious sequence homology between them .

The trans-activation domain of <protein>E2</protein> and <protein>Tax</protein> is interchangeable although they have no obvious sequence homology between them .


The viral trans-activators appear to target specific DNA binding protein such as NF-kB and Sp1 to cis-acting DNA site and promote lymphokine gene expression without TCR -mediated stimulation .

The <protein>viral trans-activators</protein> appear to target specific <protein>DNA binding protein</protein> such as <protein>NF-kB</protein> and <protein>Sp1</protein> to <dna>cis-acting DNA site</dna> and promote <dna>lymphokine gene</dna> expression without <protein>TCR</protein> -mediated stimulation .


Mutations in the Pit-1 gene in children with combined pituitary hormone deficiency .

Mutations in the <dna>Pit-1 gene</dna> in children with combined pituitary hormone deficiency .


Pit-1 is a pituitary-specific transcription factor that binds to and transactivates promoters of growth hormone and prolactin genes .

<protein>Pit-1</protein> is a <protein>pituitary-specific transcription factor</protein> that binds to and transactivates <dna>promoters</dna> of <dna>growth hormone and prolactin genes</dna> .


In three unrelated Japanese children with combined pituitary hormone deficiency , we identified three point mutations in the Pit-1 gene , Pro24Leu , Arg143Gln , and Arg271Trp , located on the major transactivation region , POU-specific domain , and POU-homeodomain , respectively .

In three unrelated Japanese children with combined pituitary hormone deficiency , we identified three point mutations in the <dna>Pit-1 gene</dna> , <dna>Pro24Leu</dna> , <dna>Arg143Gln</dna> , and <dna>Arg271Trp</dna> , located on the <dna>major transactivation region</dna> , <dna>POU-specific domain</dna> , and <dna>POU-homeodomain</dna> , respectively .


Activation of protein kinase C and elevation of cAMP interact synergistically to raise c-Fos and AP-1 activity in Jurkat cells .

Activation of <protein>protein kinase C</protein> and elevation of cAMP interact synergistically to raise <protein>c-Fos</protein> and <protein>AP-1</protein> activity in Jurkat cells .


We have earlier found that in Jurkat cells activation of protein kinase C ( PKC ) enhances the cyclic adenosine monophosphate ( cAMP ) accumulation induced by adenosine receptor stimulation or activation of Gs .

We have earlier found that in Jurkat cells activation of <protein>protein kinase C</protein> ( <protein>PKC</protein> ) enhances the cyclic adenosine monophosphate ( cAMP ) accumulation induced by adenosine receptor stimulation or activation of <protein>Gs</protein> .


Here we have therefore examined the effect of the phorbol ester PMA ( phorbol 12-myristate 13-acetate ) which stimulates PKC and a combination of the adenosine receptor agonist NECA ( 5'- ( N-ethyl ) -carboxamido adenosine ) and forskolin to raise cAMP , on the levels of c-Fos and Jun and on the binding and transcriptional activity of the transcription factor , activator protein-1 ( AP-1 ) .

Here we have therefore examined the effect of the phorbol ester PMA ( phorbol 12-myristate 13-acetate ) which stimulates <protein>PKC</protein> and a combination of the <protein>adenosine receptor</protein> agonist NECA ( 5'- ( N-ethyl ) -carboxamido adenosine ) and forskolin to raise cAMP , on the levels of <protein>c-Fos</protein> and <protein>Jun</protein> and on the binding and transcriptional activity of the <protein>transcription factor</protein> , <protein>activator protein-1</protein> ( <protein>AP-1</protein> ) .


PMA treatment caused a concentration- and time-dependent increase in both c-Fos and Jun immunoreactivity in contrast to cAMP elevation that had only a slight effect .


Both PMA and the combination of NECA and forskolin acted together either to increase ( c-Fos ) or decrease ( Jun ) protein levels as well as increasing AP-1 binding , as judged by gel-shift assay , and AP-1 transcriptional activity .

Both PMA and the combination of NECA and forskolin acted together either to increase ( <protein>c-Fos</protein> ) or decrease ( <protein>Jun</protein> ) protein levels as well as increasing <protein>AP-1</protein> binding , as judged by gel-shift assay , and <protein>AP-1</protein> transcriptional activity .


Furthermore there was a clear-cut synergy between the PKC stimulator and the cAMP elevating agents .

Furthermore there was a clear-cut synergy between the <protein>PKC</protein> stimulator and the cAMP elevating agents .


The results demonstrate that the simultaneous activation of PKC and elevation of cAMP leads to an enhanced AP-1 transcriptional activity in a T-leukemia cell line , suggesting that the previously observed interaction between the parallel signal transduction pathways may have functional consequences at the level of gene transcription .

The results demonstrate that the simultaneous activation of <protein>PKC</protein> and elevation of cAMP leads to an enhanced <protein>AP-1</protein> transcriptional activity in a <cell_line>T-leukemia cell line</cell_line> , suggesting that the previously observed interaction between the parallel signal transduction pathways may have functional consequences at the level of gene transcription .


Inhibition of anti-CD3 monoclonal antibody -induced T-cell proliferation by dexamethasone , isoproterenol , or prostaglandin E2 either alone or in combination .

Inhibition of <protein>anti-CD3 monoclonal antibody</protein> -induced T-cell proliferation by dexamethasone , isoproterenol , or prostaglandin E2 either alone or in combination .


1 .


The purpose of these studies was to investigate the modulation of the proliferation of human T cells obtained from peripheral blood by dexamethasone ( DEX ) , isoproterenol ( ISO ) , and prostaglandin E2 ( PGE2 ) .

The purpose of these studies was to investigate the modulation of the proliferation of <cell_type>human T cells</cell_type> obtained from peripheral blood by dexamethasone ( DEX ) , isoproterenol ( ISO ) , and prostaglandin E2 ( PGE2 ) .


The former two substances interact with T cells via the glucocorticoid and beta-adrenergic receptors respectively .

The former two substances interact with <cell_type>T cells</cell_type> via the <protein>glucocorticoid and beta-adrenergic receptors</protein> respectively .


When occupied by their natural ligands , glucocorticosteroids and catecholamines , these receptors have a role in modulating T-cell function during stress .


During the inflammatory response increased levels of PGE2 bind to their receptors on T cells and thus alter responsiveness .

During the inflammatory response increased levels of PGE2 bind to their receptors on <cell_type>T cells</cell_type> and thus alter responsiveness .


Proliferation of T cells was induced by immobilized anti-CD3 monoclonal antibody ( mAb ) in the presence or absence of an additional costimulatory signal delivered by anti-CD28 mAb .

Proliferation of <cell_type>T cells</cell_type> was induced by immobilized <protein>anti-CD3 monoclonal antibody</protein> ( <protein>mAb</protein> ) in the presence or absence of an additional costimulatory signal delivered by <protein>anti-CD28 mAb</protein> .


2 .


Various physiologic concentrations of DEX , ISO , or PGE2 were added at the time of initiation of the cultures and subsequent proliferation of the unstimulated T cells was determined .

Various physiologic concentrations of DEX , ISO , or PGE2 were added at the time of initiation of the cultures and subsequent proliferation of the unstimulated <cell_type>T cells</cell_type> was determined .


The results demonstrate that physiologic concentrations of all three of these agents inhibit the anti-CD3 mAb -induced proliferation of T cells .

The results demonstrate that physiologic concentrations of all three of these agents inhibit the <protein>anti-CD3 mAb</protein> -induced proliferation of <cell_type>T cells</cell_type> .


3 .


Although DEX and PGE2 were equipotent in suppressing T-cell proliferation , ISO was much less effective .


4 .


Because concomitant elevations in the peripheral levels of these substances may occur , experiments were performed to determine the T-cell inhibitory effects of DEX together with either PGE2 or ISO .


Synergistic suppression of T-cell proliferation was observed when various concentrations of DEX and PGE2 , but not DEX and ISO , were added to cultures .


This synergistic suppression could not be explained by an increase in cAMP accumulation in T cells stimulated with DEX and PGE2 .

This synergistic suppression could not be explained by an increase in cAMP accumulation in <cell_type>T cells</cell_type> stimulated with DEX and PGE2 .


5 .


Finally , the addition of anti-CD28 mAb to anti-CD3 mAb-stimulated T cells overcame much of the suppression of proliferation induced by PGE2 or ISO but less so than that induced by DEX .

Finally , the addition of <protein>anti-CD28 mAb</protein> to <cell_type>anti-CD3 mAb-stimulated T cells</cell_type> overcame much of the suppression of proliferation induced by PGE2 or ISO but less so than that induced by DEX .


In vivo footprint analysis of the HLA-DRA gene promoter : cell-specific interaction at the octamer site and up-regulation of X box binding by interferon gamma .

In vivo footprint analysis of the <dna>HLA-DRA gene promoter</dna> : cell-specific interaction at the <dna>octamer site</dna> and up-regulation of X box binding by <protein>interferon gamma</protein> .


Analysis of the major histocompatibility complex class II gene promoter DRA has previously identified at least five cis-acting regions required for maximal expression .

Analysis of the <dna>major histocompatibility complex class II gene promoter</dna> <dna>DRA</dna> has previously identified at least five <dna>cis-acting regions</dna> required for maximal expression .


We have examined the DRA promoter for protein-DNA interactions in the intact cell , which may mediate transcriptional activation .

We have examined the <dna>DRA promoter</dna> for protein-DNA interactions in the <cell_type>intact cell</cell_type> , which may mediate transcriptional activation .


Using in vivo genomic footprinting we identified interactions in B-cell lines at the octamer site and the Y , X1 , and X2 boxes .

Using in vivo genomic footprinting we identified interactions in <cell_line>B-cell lines</cell_line> at the <dna>octamer site</dna> and the <dna>Y , X1 , and X2 boxes</dna> .


Class II antigen expressing T-cell lines maintained contacts identical to B-cell lines , while class II-negative T-cell lines exhibited no interactions .

<cell_line>Class II antigen expressing T-cell lines</cell_line> maintained contacts identical to <cell_line>B-cell lines</cell_line> , while <cell_line>class II-negative T-cell lines</cell_line> exhibited no interactions .


In lymphoid cell lines , the octamer site is occupied and required for maximal expression .

In <cell_line>lymphoid cell lines</cell_line> , the <dna>octamer site</dna> is occupied and required for maximal expression .


This is most likely due to the presence of the lymphoid-specific OTF-2 factor .

This is most likely due to the presence of the <protein>lymphoid-specific OTF-2 factor</protein> .


In contrast , the class II-positive nonlymphoid glioblastoma cell line does not exhibit interactions at the octamer site despite the presence of the ubiquitous OTF-1 factor and an open binding site .

In contrast , the <cell_line>class II-positive nonlymphoid glioblastoma cell line</cell_line> does not exhibit interactions at the <dna>octamer site</dna> despite the presence of the <protein>ubiquitous OTF-1 factor</protein> and an <dna>open binding site</dna> .


Thus , the DRA promoter discriminates against OTF-1 activation at the level of DNA binding in the glioblastoma line .

Thus , the <dna>DRA promoter</dna> discriminates against <protein>OTF-1</protein> activation at the level of DNA binding in the <cell_line>glioblastoma line</cell_line> .


Interferon gamma induces class II expression in this glioblastoma cell line and , in parallel , up-regulates X1 and X2 box protein-DNA interactions , while all other interactions remain unchanged .

<protein>Interferon gamma</protein> induces class II expression in this <cell_line>glioblastoma cell line</cell_line> and , in parallel , up-regulates X1 and X2 box protein-DNA interactions , while all other interactions remain unchanged .


These results suggest that interferon gamma functions on a poised promoter by altering weak , nonproductive interactions at the X boxes to strong interactions .

These results suggest that <protein>interferon gamma</protein> functions on a <dna>poised promoter</dna> by altering weak , nonproductive interactions at the <dna>X boxes</dna> to strong interactions .


These findings provide direct in vivo evidence to strongly suggest that the modulation of X1 and X2 interactions is an important constituent of the interferon gamma induction pathway .

These findings provide direct in vivo evidence to strongly suggest that the modulation of <dna>X1</dna> and <dna>X2</dna> interactions is an important constituent of the <protein>interferon gamma</protein> induction pathway .


Estrogen binding sites in peripheral blood monocytes and effects of danazol on their sites in vitro .

Estrogen binding sites in <cell_type>peripheral blood monocytes</cell_type> and effects of danazol on their sites in vitro .


1 .


This study was designed to investigate the presence of estrogen type I ( high affinity , low capacity ) and type II ( low affinity , high capacity ) binding sites in human peripheral blood monocytes and the effects of danazol on these sites .

This study was designed to investigate the presence of estrogen type I ( high affinity , low capacity ) and type II ( low affinity , high capacity ) binding sites in human <cell_type>peripheral blood monocytes</cell_type> and the effects of danazol on these sites .


2 .


These two types of estrogen binding sites existed in human peripheral blood monocytes .

These two types of estrogen binding sites existed in <cell_type>human peripheral blood monocytes</cell_type> .


3 .


Danazol bound to these sites in high concentration ( 10 ( -6 ) M , clinical serum concentration during danazol therapy ) and decreased the number of both sites .


4 .


It is suggested that danazol has an anti-estrogenic action to the monocytes through the competition and suppression of estrogen binding sites as seen in the estrogen target organ .


A microtitre assay system for glucocorticoid receptors : decreased receptor concentration in myocardial infarction .

A microtitre assay system for <protein>glucocorticoid receptors</protein> : decreased receptor concentration in myocardial infarction .


A major difficulty in determination of glucocorticoid receptor sites is the very complicated assay procedure .


Therefore , we describe a microtitre assay system for glucocorticoid receptors which is a whole-cell competitive binding radioassay using [ 3H ] -dexamethasone as radioligand .

Therefore , we describe a microtitre assay system for <protein>glucocorticoid receptors</protein> which is a whole-cell competitive binding radioassay using [ 3H ] -dexamethasone as radioligand .


This modification of a previously described protocol simplifies and reduces laboratory work and allows assay reproducibility to be controlled more reliably .


Thus enabled to perform the test on multiple blood samples in parallel , we investigated cardiac infarction patients over a 12-day period to test if glucocorticoid receptor binding is altered in this 'stressful ' disease .

Thus enabled to perform the test on multiple <cell_type>blood samples</cell_type> in parallel , we investigated cardiac infarction patients over a 12-day period to test if <protein>glucocorticoid receptor</protein> binding is altered in this 'stressful ' disease .


On the first day of the disease , glucocorticoid receptor capacity was significantly decreased without alteration of the receptor-ligand affinity , whereas on days 4 and 12 the number of receptor sites was normal again .

On the first day of the disease , <protein>glucocorticoid receptor</protein> capacity was significantly decreased without alteration of the receptor-ligand affinity , whereas on days 4 and 12 the number of receptor sites was normal again .


This result fits well into the general observation of stress-induced down-regulation of immune responses .


SRC-related proto-oncogenes and transcription factors in primary human T cells : modulation by cyclosporin A and FK506 .

<dna>SRC-related proto-oncogenes</dna> and <protein>transcription factors</protein> in primary <cell_type>human T cells</cell_type> : modulation by cyclosporin A and FK506 .


Activation of T lymphocytes induces transcription of genes encoding for lymphokines .

Activation of <cell_type>T lymphocytes</cell_type> induces transcription of <dna>genes</dna> encoding for <protein>lymphokines</protein> .


Interleukin-2 ( IL-2 ) gene expression is controlled transcriptionally by the cooperative activity of specific trans-activating factors that bind to the IL-2 enhancer .

<dna>Interleukin-2 ( IL-2 ) gene</dna> expression is controlled transcriptionally by the cooperative activity of specific <protein>trans-activating factors</protein> that bind to the <dna>IL-2 enhancer</dna> .


Cyclosporin A ( CsA ) and FK506 inhibit the production of IL-2 in T lymphocytes at the level of gene transcription .

Cyclosporin A ( CsA ) and FK506 inhibit the production of <protein>IL-2</protein> in <cell_type>T lymphocytes</cell_type> at the level of gene transcription .


A member of the src gene family , the lymphocyte-specific protein tyrosine kinase , p56lck , has been implicated in IL-2 production .

A member of the <dna>src gene family</dna> , the <protein>lymphocyte-specific protein tyrosine kinase</protein> , <protein>p56lck</protein> , has been implicated in <protein>IL-2</protein> production .


CsA was found not to inhibit lck gene expression , nor the activity of the lck gene product .

CsA was found not to inhibit <protein>lck</protein> gene expression , nor the activity of the <dna>lck gene</dna> product .


However , CsA and FK506 inhibit the appearance of DNA binding activity of factors that bind to the NF-AT and AP-1 sites in the IL-2 enhancer .

However , CsA and FK506 inhibit the appearance of DNA binding activity of factors that bind to the <dna>NF-AT</dna> and <dna>AP-1 sites</dna> in the <dna>IL-2 enhancer</dna> .


Since the induction of NF-AT and AP-1 is induced by the same stimuli that stimulate IL-2 production , these results indicate that the immunosuppressant action of CsA and FK506 is exerted at the level of these trans-activating factors .

Since the induction of <protein>NF-AT</protein> and <protein>AP-1</protein> is induced by the same stimuli that stimulate <protein>IL-2</protein> production , these results indicate that the immunosuppressant action of CsA and FK506 is exerted at the level of these <protein>trans-activating factors</protein> .


The AP-1 site at -150 bp , but not the NF-kappa B site , is likely to represent the major target of protein kinase C in the interleukin 2 promoter .

The <dna>AP-1 site</dna> at <dna>-150 bp</dna> , but not the <dna>NF-kappa B site</dna> , is likely to represent the major target of <protein>protein kinase C</protein> in the <dna>interleukin 2 promoter</dna> .


Stimulation of T cells with antigen results in activation of several kinases , including protein kinase C ( PKC ) , that may mediate the later induction of activation-related genes .

Stimulation of <cell_type>T cells</cell_type> with antigen results in activation of several <protein>kinases</protein> , including <protein>protein kinase C</protein> ( <protein>PKC</protein> ) , that may mediate the later induction of activation-related genes .


We have examined the potential role of PKC in induction of the interleukin 2 ( IL-2 ) gene in T cells stimulated through the T cell receptor/CD3 complex .

We have examined the potential role of <protein>PKC</protein> in induction of the <dna>interleukin 2 ( IL-2 ) gene</dna> in <cell_type>T cells</cell_type> stimulated through the <protein>T cell receptor/CD3 complex</protein> .


We have previously shown that prolonged treatment of the untransformed T cell clone Ar-5 with phorbol esters results in downmodulation of the alpha and beta isozymes of PKC , and abrogates induction of IL-2 mRNA and protein .

We have previously shown that prolonged treatment of the untransformed <cell_line>T cell clone Ar-5</cell_line> with phorbol esters results in downmodulation of the <protein>alpha and beta isozymes</protein> of <protein>PKC</protein> , and abrogates induction of <rna>IL-2 mRNA</rna> and <protein>protein</protein> .


Here we show that phorbol ester treatment also abolishes induction of chloramphenicol acetyltransferase activity in Ar-5 cells transfected with a plasmid containing the IL-2 promoter linked to this reporter gene .

Here we show that phorbol ester treatment also abolishes induction of <protein>chloramphenicol acetyltransferase</protein> activity in <cell_line>Ar-5 cells</cell_line> transfected with a <dna>plasmid</dna> containing the <dna>IL-2 promoter</dna> linked to this <dna>reporter gene</dna> .


The IL-2 promoter contains binding sites for nuclear factors including NFAT-1 , Oct , NF-kappa B , and AP-1 , which are all potentially sensitive to activation of PKC .

The <dna>IL-2 promoter</dna> contains <dna>binding sites</dna> for <protein>nuclear factors</protein> including <protein>NFAT-1</protein> , <protein>Oct</protein> , <protein>NF-kappa B</protein> , and <protein>AP-1</protein> , which are all potentially sensitive to activation of <protein>PKC</protein> .


We show that induction of a trimer of the NFAT and Oct sites is not sensitive to phorbol ester treatment , and that mutations in the NF-kappa B site have no effect on inducibility of the IL-2 promoter .

We show that induction of a trimer of the <dna>NFAT and Oct sites</dna> is not sensitive to phorbol ester treatment , and that mutations in the <dna>NF-kappa B site</dna> have no effect on inducibility of the <dna>IL-2 promoter</dna> .


In contrast , mutations in the AP-1 site located at -150 bp almost completely abrogate induction of the IL-2 promoter , and appearance of an inducible nuclear factor binding to this site is sensitive to PKC depletion .

In contrast , mutations in the <dna>AP-1 site</dna> located at <dna>-150 bp</dna> almost completely abrogate induction of the <dna>IL-2 promoter</dna> , and appearance of an <protein>inducible nuclear factor</protein> binding to this site is sensitive to <protein>PKC</protein> depletion .


Moreover , cotransfections with c-fos and c-jun expression plasmids markedly enhance induction of the IL-2 promoter in minimally stimulated T cells .

Moreover , cotransfections with c-fos and c-jun expression plasmids markedly enhance induction of the <dna>IL-2 promoter</dna> in <cell_line>minimally stimulated T cells</cell_line> .


Our results indicate that the AP-1 site at -150 bp represents a major , if not the only , site of PKC responsiveness in the IL-2 promoter .

Our results indicate that the <dna>AP-1 site</dna> at <dna>-150 bp</dna> represents a major , if not the only , site of <protein>PKC</protein> responsiveness in the <dna>IL-2 promoter</dna> .


[ Effect of antihypertensive therapy with captopril on gluco- and mineralocorticoid receptors of peripheral blood lymphocytes in hypertensive patients of various age ]

[ Effect of antihypertensive therapy with captopril on <protein>gluco- and mineralocorticoid receptors</protein> of <cell_type>peripheral blood lymphocytes</cell_type> in hypertensive patients of various age ]


Binding of 3H-dexamethasone and 3H-aldosterone by peripheral lymphocyte receptors was investigated in healthy persons and hypertensive patients before and after 2-week captopril treatment .

Binding of 3H-dexamethasone and 3H-aldosterone by <protein>peripheral lymphocyte receptors</protein> was investigated in healthy persons and hypertensive patients before and after 2-week captopril treatment .


The number of glucocorticoid and mineralocorticoid binding sites was increased in hypertensives vs normotensives .

The number of <protein>glucocorticoid and mineralocorticoid binding sites</protein> was increased in hypertensives vs normotensives .


The treatment with the ACE inhibitor captopril led to activation of hormone-receptor interactions .


There was a more marked rise of the number of receptors in middle-aged ( 44-55 years ) hypertensives vs elderly ( 61-80 years ) subjects after captopril treatment .

There was a more marked rise of the number of <protein>receptors</protein> in middle-aged ( 44-55 years ) hypertensives vs elderly ( 61-80 years ) subjects after captopril treatment .


The use of interferon-gamma-treated U937 cells in chemiluminescence assays to detect red cell , platelet and granulocyte antibodies of potential clinical significance .

The use of <cell_line>interferon-gamma-treated U937 cells</cell_line> in chemiluminescence assays to detect <protein>red cell , platelet and granulocyte antibodies</protein> of potential clinical significance .


The chemiluminescent ( CL ) response of interferon-gamma-treated U937 ( IFN-U937 ) cells to sensitized target cells has been used to detect red cell , platelet and granulocyte antibodies .

The chemiluminescent ( CL ) response of <cell_line>interferon-gamma-treated U937 ( IFN-U937 ) cells</cell_line> to sensitized target cells has been used to detect <protein>red cell</protein> , <protein>platelet</protein> and <protein>granulocyte antibodies</protein> .


A clone of U937 cells was selected which expressed Fc receptor I ( Fc gamma RI ) and which , after incubation with IFN-gamma for 72 h , was capable of generating high levels of lucigenin-enhanced CL .

A clone of <cell_line>U937 cells</cell_line> was selected which expressed <protein>Fc receptor I</protein> ( <protein>Fc gamma RI</protein> ) and which , after incubation with <protein>IFN-gamma</protein> for 72 h , was capable of generating high levels of lucigenin-enhanced CL .


The CL responses of IFN-U937 cells and peripheral blood human monocytes to sensitized red cells , platelets or granulocytes were then compared .

The CL responses of <cell_line>IFN-U937 cells</cell_line> and <cell_type>peripheral blood human monocytes</cell_type> to <cell_type>sensitized red cells</cell_type> , <cell_type>platelets</cell_type> or <cell_type>granulocytes</cell_type> were then compared .


Assays using monocytes or IFN-U937 cells were of comparable sensitivity for detection of antibodies against all three types of target cell .

Assays using <cell_type>monocytes</cell_type> or <cell_line>IFN-U937 cells</cell_line> were of comparable sensitivity for detection of <protein>antibodies</protein> against all three types of target cell .


In addition , the use of IFN-U937 cells reduced interassay variation and simplified assay performance .

In addition , the use of <cell_line>IFN-U937 cells</cell_line> reduced interassay variation and simplified assay performance .


The potential clinical usefulness of these CL assays was suggested by the ability of both monocytes and IFN-U937 cells to respond to red cells , platelets or granulocytes sensitized with sera from pregnant women whose babies had either haemolytic disease of the newborn ( HDN ) , alloimmune thrombocytopenia or alloimmune neutropenia respectively .

The potential clinical usefulness of these CL assays was suggested by the ability of both <cell_type>monocytes</cell_type> and <cell_line>IFN-U937 cells</cell_line> to respond to <cell_type>red cells</cell_type> , <cell_type>platelets</cell_type> or <cell_type>granulocytes</cell_type> sensitized with sera from pregnant women whose babies had either haemolytic disease of the newborn ( HDN ) , alloimmune thrombocytopenia or alloimmune neutropenia respectively .


In addition , monocytes and IFN-U937 cells both responded to red cells sensitized with antibodies against a variety of specificities of assumed ( although not documented ) clinical significance for blood transfusion recipients .

In addition , <cell_type>monocytes</cell_type> and <cell_line>IFN-U937 cells</cell_line> both responded to <cell_type>red cells</cell_type> sensitized with <protein>antibodies</protein> against a variety of specificities of assumed ( although not documented ) clinical significance for blood transfusion recipients .


In contrast , monocytes and IFN-U937 cells responded only weakly to red cells sensitized with either anti-D in sera from mothers of babies unaffected by HDN , or with antisera containing high titre antibodies with specificities not normally associated with significantly reduced red cell survival .

In contrast , <cell_type>monocytes</cell_type> and <cell_line>IFN-U937 cells</cell_line> responded only weakly to <cell_type>red cells</cell_type> sensitized with either <protein>anti-D</protein> in sera from mothers of babies unaffected by HDN , or with antisera containing <protein>high titre antibodies</protein> with specificities not normally associated with significantly reduced <cell_type>red cell</cell_type> survival .


Ablation of transplanted HTLV-I Tax-transformed tumors in mice by antisense inhibition of NF-kappa B [ published erratum appears in Science 1993 Mar 12 ; 259 ( 5101 ) : 1523 ]

Ablation of transplanted HTLV-I Tax-transformed tumors in mice by antisense inhibition of <protein>NF-kappa B</protein> [ published erratum appears in Science 1993 Mar 12 ; 259 ( 5101 ) : 1523 ]


Mice transgenic for the human T cell leukemia virus ( HTLV-I ) Tax gene develop fibroblastic tumors that express NF-kappa B-inducible early genes .

Mice transgenic for the <dna>human T cell leukemia virus ( HTLV-I ) Tax gene</dna> develop fibroblastic tumors that express <dna>NF-kappa B-inducible early genes</dna> .


In vitro inhibition of NF-kappa B expression by antisense oligodeoxynucleotides ( ODNs ) inhibited growth of these culture-adapted Tax-transformed fibroblasts as well as an HTLV-I-transformed human lymphocyte line .

In vitro inhibition of <protein>NF-kappa B</protein> expression by antisense oligodeoxynucleotides ( ODNs ) inhibited growth of these <cell_line>culture-adapted Tax-transformed fibroblasts</cell_line> as well as an <cell_line>HTLV-I-transformed human lymphocyte line</cell_line> .


In contrast , antisense inhibition of Tax itself had no apparent effect on cell growth .

In contrast , antisense inhibition of <protein>Tax</protein> itself had no apparent effect on cell growth .


Mice treated with antisense to NF-kappa B ODNs showed rapid regression of transplanted fibrosarcomas .

Mice treated with antisense to <protein>NF-kappa B</protein> ODNs showed rapid regression of transplanted fibrosarcomas .


This suggests that NF-kappa B expression may be necessary for the maintenance of the malignant phenotype and provides a therapeutic approach for HTLV-I-associated disease .

This suggests that <protein>NF-kappa B</protein> expression may be necessary for the maintenance of the malignant phenotype and provides a therapeutic approach for HTLV-I-associated disease .


Membrane receptors for aldosterone : a novel pathway for mineralocorticoid action .

<protein>Membrane receptors</protein> for aldosterone : a novel pathway for mineralocorticoid action .


Rapid nongenomic in vitro effects of aldosterone on intracellular electrolytes , cell volume , and Na ( + ) -H+ antiport have been found in human mononuclear leukocytes ( HML ) .

Rapid nongenomic in vitro effects of aldosterone on intracellular electrolytes , cell volume , and <protein>Na ( + ) -H+ antiport</protein> have been found in <cell_type>human mononuclear leukocytes</cell_type> ( <cell_type>HML</cell_type> ) .


Binding of 125I-labeled aldosterone to plasma membranes of HML shares important features with these functional data .

Binding of 125I-labeled aldosterone to plasma membranes of <cell_type>HML</cell_type> shares important features with these functional data .


This includes a very low apparent dissociation constant ( Kd ) of 0.1 nM for both aldosterone and the effect on the Na ( + ) -H ( + ) -antiport , a high turnover rate , and the almost exclusive binding selectivity for aldosterone .

This includes a very low apparent dissociation constant ( Kd ) of 0.1 nM for both aldosterone and the effect on the <protein>Na ( + ) -H ( + ) -antiport</protein> , a high turnover rate , and the almost exclusive binding selectivity for aldosterone .


Dexamethasone , RU 26988 , corticosterone , ouabain , amiloride , and 18-hydroxyprogesterone were inactive as ligands .


Deoxycorticosterone acetate had an intermediate activity with an apparent Kd of 100 nM .


These findings are the first to demonstrate membrane binding of aldosterone being compatible with major aspects of its nongenomic effects .


Leukotriene B4 transcriptionally activates interleukin-6 expression involving NK-chi B and NF-IL6 .

Leukotriene B4 transcriptionally activates <protein>interleukin-6</protein> expression involving <protein>NK-chi B</protein> and <protein>NF-IL6</protein> .


Leukotriene B4 ( LTB4 ) is a notable participant in inflammation and chemotaxis .


It is , however , still unclear whether LTB4 acts in this regard directly or indirectly by stimulating the release of chemotactic and inflammatory cytokines .

It is , however , still unclear whether LTB4 acts in this regard directly or indirectly by stimulating the release of chemotactic and <protein>inflammatory cytokines</protein> .


Here we report that LTB4 induces synthesis of interleukin ( IL ) -6 by human blood monocytes through transcriptional activation of the IL-6 gene .

Here we report that LTB4 induces synthesis of <protein>interleukin ( IL ) -6</protein> by <cell_type>human blood monocytes</cell_type> through transcriptional activation of the <dna>IL-6 gene</dna> .


We furthermore demonstrate that this process involves activation of the transcription factor NF-chi B and , to a lesser extent , of NF-IL6 , while the activity of the transcription factor AP-1 , shown to otherwise confer IL-6 inducibility , appeared to be unaffected by LTB4 .

We furthermore demonstrate that this process involves activation of the <protein>transcription factor</protein> <protein>NF-chi B</protein> and , to a lesser extent , of <protein>NF-IL6</protein> , while the activity of the <protein>transcription factor</protein> <protein>AP-1</protein> , shown to otherwise confer <protein>IL-6</protein> inducibility , appeared to be unaffected by LTB4 .


Involvement of NF-chi B and NF-IL6 in induction of IL-6 transcription by monocytes was demonstrated using deleted forms of the IL-6 promoter .

Involvement of <protein>NF-chi B</protein> and <protein>NF-IL6</protein> in induction of <protein>IL-6</protein> transcription by monocytes was demonstrated using deleted forms of the <dna>IL-6 promoter</dna> .


Activation of the IL-6 promoter by LTB4 was not only associated with accumulation of the respective transcripts but resulted in synthesis of functional IL-6 protein as well .

Activation of the <dna>IL-6 promoter</dna> by LTB4 was not only associated with accumulation of the respective transcripts but resulted in synthesis of functional <protein>IL-6 protein</protein> as well .


In addition , LTB4 mediated transactivation of a heterologous promoter construct containing the NF-chi B or the NF-IL6 enhancer , but not the AP-1 enhancer .

In addition , LTB4 mediated transactivation of a <dna>heterologous promoter construct</dna> containing the <dna>NF-chi B</dna> or the <dna>NF-IL6 enhancer</dna> , but not the <dna>AP-1 enhancer</dna> .


The signaling events mediating this effect appeared to involve the release of H2O2 , since LTB4 failed to induce NF-chi B or NF-IL6 in the presence of the scavenger of H2O2 , N-acetyl-L-cysteine .

The signaling events mediating this effect appeared to involve the release of H2O2 , since LTB4 failed to induce <protein>NF-chi B</protein> or <protein>NF-IL6</protein> in the presence of the scavenger of H2O2 , N-acetyl-L-cysteine .


Bcl-2 : a repressor of lymphocyte death .

<protein>Bcl-2</protein> : a repressor of <cell_type>lymphocyte</cell_type> death .


The genes and mechanisms that control programmed cell death are currently the subject of intense study .


The bcl-2 gene , a repressor of lymphocyte death , is perhaps the best understood of the programmed cell death associated genes .

The <dna>bcl-2 gene</dna> , a repressor of <cell_type>lymphocyte</cell_type> death , is perhaps the best understood of the programmed cell death associated genes .


Here , Stanley Korsmeyer provides a brief overview of bcl-2 , concentrating on its roles in B- and T-cell development and in oncogenesis .

Here , Stanley Korsmeyer provides a brief overview of <protein>bcl-2</protein> , concentrating on its roles in B- and T-cell development and in oncogenesis .


Cytoplasmic domain heterogeneity and functions of IgG Fc receptors in B lymphocytes .

Cytoplasmic domain heterogeneity and functions of <protein>IgG Fc receptors</protein> in <cell_type>B lymphocytes</cell_type> .


B lymphocytes and macrophages express closely related immunoglobulin G ( IgG ) Fc receptors ( Fc gamma RII ) that differ only in the structures of their cytoplasmic domains .

<cell_type>B lymphocytes</cell_type> and macrophages express closely related <protein>immunoglobulin G ( IgG ) Fc receptors</protein> ( <protein>Fc gamma RII</protein> ) that differ only in the structures of their <protein>cytoplasmic domains</protein> .


Because of cell type-specific alternative messenger RNA splicing , B-cell Fc gamma RII contains an insertion of 47 amino acids that participates in determining receptor function in these cells .

Because of cell type-specific alternative messenger RNA splicing , <protein>B-cell Fc gamma RII</protein> contains an insertion of 47 amino acids that participates in determining receptor function in these cells .


Transfection of an Fc gamma RII-negative B-cell line with complementary DNA 's encoding the two splice products and various receptor mutants indicated that the insertion was responsible for preventing both Fc gamma RII -mediated endocytosis and Fc gamma RII -mediated antigen presentation .

Transfection of an <cell_line>Fc gamma RII-negative B-cell line</cell_line> with complementary DNA 's encoding the two splice products and various receptor mutants indicated that the insertion was responsible for preventing both <protein>Fc gamma RII</protein> -mediated endocytosis and <protein>Fc gamma RII</protein> -mediated antigen presentation .


The insertion was not required for Fc gamma RII to modulate surface immunoglobulin -triggered B-cell activation .

The insertion was not required for <protein>Fc gamma RII</protein> to modulate <protein>surface immunoglobulin</protein> -triggered B-cell activation .


Instead , regulation of activation involved a region of the cytoplasmic domain common to both the lymphocyte and macrophage receptor isoforms .

Instead , regulation of activation involved a region of the <protein>cytoplasmic domain</protein> common to both the <protein>lymphocyte and macrophage receptor isoforms</protein> .


In contrast , the insertion did contribute to the formation of caps in response to receptor cross-linking , consistent with suggestions that the lymphocyte but not macrophage form of the receptor can associate with the detergent-insoluble cytoskeleton .


[ Age-related changes in glucocorticoid and mineralocorticoid receptors in lymphocytes of healthy persons and patients with hypertension ]

[ Age-related changes in <protein>glucocorticoid and mineralocorticoid receptors</protein> in <cell_type>lymphocytes</cell_type> of healthy persons and patients with hypertension ]


It has been found that the number of glucocorticoid receptors in lymphocytes of the peripheral blood of healthy elderly subjects increases , while the number of mineralocorticoid receptors decreases .

It has been found that the number of <protein>glucocorticoid receptors</protein> in <cell_type>lymphocytes</cell_type> of the peripheral blood of healthy elderly subjects increases , while the number of mineralocorticoid receptors decreases .


The mechanisms of hormone-receptor interactions in hypertension are activated : the number of glucocorticoid and mineralocorticoid binding sites grows in hypertensive patients .

The mechanisms of hormone-receptor interactions in hypertension are activated : the number of <protein>glucocorticoid and mineralocorticoid binding sites</protein> grows in hypertensive patients .


Still a more essential rise in the number of receptors is observed in mid-age hypertensive patients than in elderly ones .


The mechanism of action of cyclosporin A and FK506 .


CsA and FK506 are powerful suppressors of the immune system , most notably of T cells .

CsA and FK506 are powerful suppressors of the immune system , most notably of <cell_type>T cells</cell_type> .


They act at a point in activation that lies between receptor ligation and the transcription of early genes .

They act at a point in activation that lies between receptor ligation and the transcription of <dna>early genes</dna> .


Here , Stuart Schreiber and Gerald Crabtree review recent findings that indicate CsA and FK506 operate as prodrugs : they bind endogenous intracellular receptors , the immunophilins , and the resulting complex targets the protein phosphatase , calcineurin , to exert the immunosuppressive effect .

Here , Stuart Schreiber and Gerald Crabtree review recent findings that indicate CsA and FK506 operate as prodrugs : they bind <protein>endogenous intracellular receptors</protein> , the <protein>immunophilins</protein> , and the resulting complex targets the <protein>protein phosphatase ,</protein> <protein>calcineurin</protein> , to exert the immunosuppressive effect .


Induction of monocytic differentiation and NF-kappa B -like activities by human immunodeficiency virus 1 infection of myelomonoblastic cells .

Induction of monocytic differentiation and <protein>NF-kappa B</protein> -like activities by human immunodeficiency virus 1 infection of <cell_type>myelomonoblastic cells</cell_type> .


The effects of human immunodeficiency virus 1 ( HIV-1 ) infection on cellular differentiation and NF-kappa B DNA binding activity have been investigated in a new model of myeloid differentiation .

The effects of human immunodeficiency virus 1 ( HIV-1 ) infection on cellular differentiation and <protein>NF-kappa B</protein> DNA binding activity have been investigated in a new model of myeloid differentiation .