The extracellular domain of the murine G-CSF receptor was required for the activity of SB 247464 , suggesting that the compound acts by oligomerizing receptor chains .

The extracellular domain of the <protein>murine G-CSF receptor</protein> was required for the activity of SB 247464 , suggesting that the compound acts by <protein>oligomerizing receptor chains</protein> .


The results indicate that a small molecule can activate a receptor that normally binds a relatively large protein ligand .


Minimal residual disease in acute myelogenous leukemia with PML/RAR alpha or AML1/ETO mRNA and phenotypic analysis of possible T and natural killer cells in bone marrow .

Minimal residual disease in acute myelogenous leukemia with <protein>PML/RAR alpha</protein> or <rna>AML1/ETO mRNA</rna> and phenotypic analysis of possible <cell_type>T and natural killer cells</cell_type> in bone marrow .


Here we studied minimal residual disease ( MRD ) of patients with acute myeloid leukemia ( AML ) who have PML/RAR alpha or AML1/ETO as well as the phenotypic analysis of lymphocyte subsets involved in antitumor immunity .

Here we studied minimal residual disease ( MRD ) of patients with acute myeloid leukemia ( AML ) who have <protein>PML/RAR alpha</protein> or <protein>AML1/ETO</protein> as well as the phenotypic analysis of <cell_type>lymphocyte subsets</cell_type> involved in antitumor immunity .


Eight patients in long-term ( LT ; 3 to 15 years ) and 15 patients in short-term ( ST ; up to 3 years ) remission were studied .


Using the reverse transcription-polymerase chain reaction ( RT ) assay , the limit of detection was 10 ( -5 ) to 10 ( -6 ) for PML/RAR alpha transcript and 10 ( -4 ) to 10 ( -5 ) for the AML1/ETO transcript .

Using the reverse transcription-polymerase chain reaction ( RT ) assay , the limit of detection was 10 ( -5 ) to 10 ( -6 ) for <rna>PML/RAR alpha transcript</rna> and 10 ( -4 ) to 10 ( -5 ) for the <rna>AML1/ETO transcript</rna> .


Simultaneously , T lymphocyte subsets and NK cells from the peripheral blood ( PB ) and bone marrow ( BM ) were investigated by flow cytometric analysis .

Simultaneously , <cell_type>T lymphocyte subsets</cell_type> and <cell_type>NK cells</cell_type> from the peripheral blood ( PB ) and bone marrow ( BM ) were investigated by flow cytometric analysis .


Four of the eight patients in LT and 7 of the 15 patients in ST remission were MRD-positive .


Although all MRD-positive patients in LT remission are still until now event-free , 3 of the 7 MRD-positive ( MRD+ ) patients in ST remission soon relapsed .


The total populations of CD4 + , CD8 + and CD56 + [ possible T-cell and natural killer ( T/NK ) populations ] in the BM of ST patients and MRD+/LT patients were significantly ( p < .01 ) low .

The total populations of <protein>CD4</protein> + , <protein>CD8</protein> + and <protein>CD56</protein> + [ possible <cell_type>T-cell and natural killer ( T/NK ) populations</cell_type> ] in the BM of ST patients and MRD+/LT patients were significantly ( p < .01 ) low .


The CD8+ CD28+ population showed the same tendency ( p < .01-.02 ) .

The <cell_type>CD8+ CD28+ population</cell_type> showed the same tendency ( p < .01-.02 ) .


The T/NK subsets in the BM of MRD-negative ( MRD- ) LT ( MRD-/LT ) patients showed similar numbers of cells as normal volunteers .

The <cell_type>T/NK subsets</cell_type> in the BM of MRD-negative ( MRD- ) LT ( MRD-/LT ) patients showed similar numbers of cells as normal volunteers .


Basically , the total percentage of the CD4+ , CD8+ and CD56+ cell populations in the BM was increased and in the following order : MRD-/LT patients , normal volunteers , MRD+/LT patients and MRD+ or -/ST patients .

Basically , the total percentage of the <cell_type>CD4+ , CD8+ and CD56+ cell populations</cell_type> in the BM was increased and in the following order : MRD-/LT patients , normal volunteers , MRD+/LT patients and MRD+ or -/ST patients .


The percentages of the T/NK-cell subsets in the PB were not significantly different among these groups .

The percentages of the <cell_type>T/NK-cell subsets</cell_type> in the PB were not significantly different among these groups .


Thus , the difference of the possible T/NK-cell phenotype in the BM may strongly influence clinical and molecular remission .

Thus , the difference of the possible <cell_type>T/NK-cell</cell_type> phenotype in the BM may strongly influence clinical and molecular remission .


These results still remain to be confirmed by further studies of the functional anti-tumor immunity of T/NK cells of AML in remission .

These results still remain to be confirmed by further studies of the functional anti-tumor immunity of <cell_type>T/NK cells</cell_type> of <cell_type>AML</cell_type> in remission .


Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-kappaB -dependent activation of human immunodeficiency virus type 1 long terminal repeat in T cells .

Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce <protein>NF-kappaB</protein> -dependent activation of <dna>human immunodeficiency virus type 1 long terminal repeat</dna> in <cell_type>T cells</cell_type> .


Tuberculosis has emerged as an epidemic , extended by the large number of individuals infected with human immunodeficiency virus type 1 ( HIV-1 ) .


The major goal of this study was to determine whether the mycobacterial cell wall component mannose-capped lipoarabinomannan ( ManLAM ) of Mycobacterium tuberculosis ( M. tuberculosis ) could activate transcription of HIV-1 in T cells with the use of an in vitro cell culture system .

The major goal of this study was to determine whether the mycobacterial cell wall component mannose-capped lipoarabinomannan ( ManLAM ) of Mycobacterium tuberculosis ( M. tuberculosis ) could activate transcription of HIV-1 in <cell_type>T cells</cell_type> with the use of an in vitro cell culture system .


These experiments are of prime importance considering that CD4 -expressing T lymphocytes represent the major virus reservoir in the peripheral blood of infected individuals .

These experiments are of prime importance considering that <protein>CD4</protein> -expressing <cell_type>T lymphocytes</cell_type> represent the major virus reservoir in the peripheral blood of infected individuals .


Using the 1G5 cell line harbouring the luciferase reporter gene under the control of the HIV-1 LTR , it was first found that culture protein filtrates ( CFP ) from M. tuberculosis or purified ManLAM could activate HIV-1 LTR-dependent gene expression unlike similarly prepared CFP extracts devoid of ManLAM .

Using the <cell_line>1G5 cell line</cell_line> harbouring the luciferase reporter gene under the control of the <dna>HIV-1 LTR</dna> , it was first found that culture protein filtrates ( CFP ) from M. tuberculosis or purified ManLAM could activate <dna>HIV-1 LTR-dependent gene</dna> expression unlike similarly prepared CFP extracts devoid of ManLAM .


The implication of protein tyrosine kinase ( s ) , protein kinase A and/or protein kinase C was highlighted by the abrogation of the ManLAM-mediated activation of HIV-1 LTR-driven gene expression using herbimycin A and H7 .

The implication of <protein>protein tyrosine kinase ( s )</protein> , <protein>protein kinase A</protein> and/or <protein>protein kinase C</protein> was highlighted by the abrogation of the ManLAM-mediated activation of HIV-1 LTR-driven gene expression using herbimycin A and H7 .


It was also determined , using electrophoresis mobility shift assays , that M. tuberculosis ManLAM led to the nuclear translocation of the transcription factor NF-kappaB .

It was also determined , using electrophoresis mobility shift assays , that M. tuberculosis ManLAM led to the nuclear translocation of the <protein>transcription factor NF-kappaB</protein> .


M. tuberculosis ManLAM resulted in clear induction of the luciferase gene placed under the control of the wild-type , but not the kappaB-mutated , HIV-1 LTR region .

M. tuberculosis ManLAM resulted in clear induction of the <dna>luciferase gene</dna> placed under the control of the <dna>wild-type , but not the kappaB-mutated , HIV-1 LTR region</dna> .


Finally , the ManLAM-mediated activation of HIV-1 LTR transcription was found to be independent of the autocrine or paracrine action of endogenous TNF-alpha .

Finally , the ManLAM-mediated activation of HIV-1 LTR transcription was found to be independent of the autocrine or paracrine action of <protein>endogenous TNF-alpha</protein> .


The results suggest that M. tuberculosis can upregulate HIV-1 expression in T cells and could thus have the potential to influence the pathogenesis of HIV-1 infection .

The results suggest that M. tuberculosis can upregulate HIV-1 expression in <cell_type>T cells</cell_type> and could thus have the potential to influence the pathogenesis of HIV-1 infection .


Human immunodeficiency virus type 1 long terminal repeat quasispecies differ in basal transcription and nuclear factor recruitment in human glial cells and lymphocytes .

<dna>Human immunodeficiency virus type 1 long terminal repeat</dna> quasispecies differ in basal transcription and nuclear factor recruitment in <cell_type>human glial cells and lymphocytes</cell_type> .


The generation of genomic diversity during the course of infection has the potential to affect all aspects of HIV-1 replication , including expression of the proviral genome .


To gain a better understanding of the impact of long terminal repeat ( LTR ) sequence diversity on LTR-directed gene expression in cells of the central nervous system ( CNS ) and immune system , we amplified and cloned LTRs from proviral DNA in HIV-1-infected peripheral blood .

To gain a better understanding of the impact of <dna>long terminal repeat</dna> ( <dna>LTR</dna> ) sequence diversity on <dna>LTR-directed gene</dna> expression in cells of the central nervous system ( CNS ) and immune system , we amplified and cloned <dna>LTRs</dna> from proviral DNA in HIV-1-infected peripheral blood .


Sequence analysis of nineteen LTRs cloned from 2 adult and 3 pediatric patients revealed an average of 33 nucleotide changes ( with respect to the sequence of the LAI LTR ) within the 455-bp U3 region .

Sequence analysis of nineteen <dna>LTRs</dna> cloned from 2 adult and 3 pediatric patients revealed an average of 33 nucleotide changes ( with respect to the sequence of the <dna>LAI LTR</dna> ) within the <dna>455-bp U3 region</dna> .


Transient expression analyses in cells of neuroglial and lymphocytic origin demonstrated that some of these LTRs had activities which varied significantly from the LAI LTR in U-373 MG cells ( an astrocytoma cell line ) as well as in Jurkat cells ( a CD4-positive lymphocyte cell line ) .

Transient expression analyses in cells of neuroglial and lymphocytic origin demonstrated that some of these <dna>LTRs</dna> had activities which varied significantly from the <dna>LAI LTR</dna> in <cell_line>U-373 MG cells</cell_line> ( an <cell_line>astrocytoma cell line</cell_line> ) as well as in <cell_line>Jurkat cells</cell_line> ( a <cell_line>CD4-positive lymphocyte cell line</cell_line> ) .


While LTRs which demonstrated the highest activities in U-373 MG cells also yielded high activities in Jurkat cells , the LTRs were generally more active in Jurkat cells when compared to the LAI LTR .

While <dna>LTRs</dna> which demonstrated the highest activities in <cell_line>U-373 MG cells</cell_line> also yielded high activities in <cell_line>Jurkat cells</cell_line> , the <dna>LTRs</dna> were generally more active in <cell_line>Jurkat cells</cell_line> when compared to the <dna>LAI LTR</dna> .


Differences in LTR sequence also resulted in differences in transcription factor recruitment to cis-acting sites within the U3 region of the LTR , as demonstrated by electrophoretic mobility shift assays .

Differences in <dna>LTR sequence</dna> also resulted in differences in transcription factor recruitment to <dna>cis-acting sites</dna> within the <dna>U3 region</dna> of the <dna>LTR</dna> , as demonstrated by electrophoretic mobility shift assays .


In particular , naturally occurring sequence variation impacted transcription factor binding to an activating transcription factor / cAMP response element binding ( ATF / CREB ) binding site ( located between the LEF-1 and distal NF-kappaB transcription factor binding sites ) that we identified in previous studies of the HIV-1 LTR .

In particular , naturally occurring sequence variation impacted <protein>transcription factor</protein> binding to an <protein>activating transcription factor</protein> / <protein>cAMP response element binding</protein> ( <protein>ATF</protein> / <protein>CREB</protein> ) binding site ( located between the <dna>LEF-1 and distal NF-kappaB transcription factor binding sites</dna> ) that we identified in previous studies of the <dna>HIV-1 LTR</dna> .


These findings suggest that LTR sequence changes can significantly affect basal LTR function and transcription factor recruitment , which may , in turn , alter the course of viral replication in cells of CNS and immune system origin .

These findings suggest that <dna>LTR sequence</dna> changes can significantly affect basal LTR function and transcription factor recruitment , which may , in turn , alter the course of viral replication in cells of CNS and immune system origin .


HMG box containing transcription factors in lymphocyte differentiation .

<protein>HMG box containing transcription factors</protein> in <cell_type>lymphocyte</cell_type> differentiation .


The identification of the mammalian sex-determining gene Sry has led to the discovery of a large family of related ( ' HMG box ' ) transcription factors that control developmental events in yeast , C. elegans , Drosophila and vertebrates .

The identification of the <dna>mammalian sex-determining gene Sry</dna> has led to the discovery of a large family of related ( ' <protein>HMG box</protein> ' ) <protein>transcription factors</protein> that control developmental events in yeast , C. elegans , Drosophila and vertebrates .


In lymphocyte differentiation , several HMG box proteins play a decisive role .

In <cell_type>lymphocyte</cell_type> differentiation , several <protein>HMG box proteins</protein> play a decisive role .


Sox-4 is important for very early B-cell differentiation , while TCF-1 / LEF-1 play a crucial role in early thymocyte development .

<protein>Sox-4</protein> is important for very early B-cell differentiation , while <protein>TCF-1</protein> / <protein>LEF-1</protein> play a crucial role in early thymocyte development .


TCF/LEF proteins have recently been found to constitute a downstream component of the Wingless/Wnt signal transduction pathway .

<protein>TCF/LEF proteins</protein> have recently been found to constitute a downstream component of the Wingless/Wnt signal transduction pathway .


In flies , this pathway controls segment polarity ; in Xenopus it controls the definition of the body axis .


Deregulation of the pathway occurs in several human tumors .

Deregulation of the pathway occurs in several <cell_type>human tumors</cell_type> .


These insights in the molecular events that are involved in TCF/LEF function in these organisms may eventually lead to the understanding of the function of these HMG box proteins in lymphoid development

These insights in the molecular events that are involved in <protein>TCF/LEF</protein> function in these organisms may eventually lead to the understanding of the function of these <protein>HMG box proteins</protein> in lymphoid development


Transcriptional regulation by C/EBP alpha and -beta in the expression of the gene for the MRP14 myeloid calcium binding protein .

Transcriptional regulation by <protein>C/EBP alpha and -beta</protein> in the expression of the gene for the <protein>MRP14 myeloid calcium binding protein</protein> .


Transcriptional regulation of the gene for the myeloid calcium binding protein , MRP14 , was investigated in human monocytic leukemia cell lines .

Transcriptional regulation of the gene for the <protein>myeloid calcium binding protein</protein> , <protein>MRP14</protein> , was investigated in <cell_line>human monocytic leukemia cell lines</cell_line> .


The MRP14 gene was not expressed in monoblastic ML-1 cells , promonocytic U-937 cells , or promyelocytic HL-60 cells .

The <dna>MRP14 gene</dna> was not expressed in <cell_line>monoblastic ML-1 cells</cell_line> , <cell_line>promonocytic U-937 cells</cell_line> , or <cell_line>promyelocytic HL-60 cells</cell_line> .


On the other hand , the gene was expressed in monocytic THP-1 cells and in the HL-60 cells treated with 1 , 25-dihydroxyvitamin D3 ( VD3 ) .

On the other hand , the gene was expressed in <cell_line>monocytic THP-1 cells</cell_line> and in the <cell_line>HL-60 cells</cell_line> treated with 1 , 25-dihydroxyvitamin D3 ( VD3 ) .


The level of MRP14 in VD3-treated HL-60 cells was two-fold higher than that in THP-1 cells .

The level of <protein>MRP14</protein> in VD3-treated <cell_line>HL-60 cells</cell_line> was two-fold higher than that in <cell_line>THP-1 cells</cell_line> .


Among several known transcription factor binding motifs , nuclear protein ( s ) of VD3-treated HL-60 cells and THP-1 cells bound to the CCAAT/enhancer binding protein ( C/EBP ) -binding motif that was located in the upstream region of the MRP14 gene ( -81 ) , as evidenced by the competitive gel mobility-shift assay .

Among several known <dna>transcription factor binding motifs</dna> , <protein>nuclear protein ( s )</protein> of <cell_line>VD3-treated HL-60 cells and THP-1 cells</cell_line> bound to the <dna>CCAAT/enhancer binding protein ( C/EBP ) -binding motif</dna> that was located in the <dna>upstream region</dna> of the <dna>MRP14 gene</dna> ( -81 ) , as evidenced by the competitive gel mobility-shift assay .


An antibody for C/EBP alpha super-shifted the nucleoprotein complex in THP-1 cells but not in the VD3-treated HL-60 cells , whereas an antibody for C/EBP beta blocked the formation of the complex with the nuclear factor of the HL-60 cells but not with that of THP-1 cells .

An antibody for <protein>C/EBP alpha</protein> super-shifted the <protein>nucleoprotein complex</protein> in <cell_line>THP-1 cells</cell_line> but not in the <cell_line>VD3-treated HL-60 cells</cell_line> , whereas an antibody for <protein>C/EBP beta</protein> blocked the formation of the complex with the <protein>nuclear factor</protein> of the <cell_line>HL-60 cells</cell_line> but not with that of <cell_line>THP-1 cells</cell_line> .


An anti-C/EBP delta antibody had no effect on the complex in either cell .

An <protein>anti-C/EBP delta antibody</protein> had no effect on the complex in either cell .


Thus , it was concluded that C/EBP alpha and -beta were able to bind to the C/EBP motif , and that C/EBP alpha bound to the motif in THP-1 cells and C/EBP beta bound to that in the VD3-treated HL-60 cells .

Thus , it was concluded that <protein>C/EBP alpha and -beta</protein> were able to bind to the <protein>C/EBP motif</protein> , and that <protein>C/EBP alpha</protein> bound to the motif in <cell_line>THP-1 cells</cell_line> and <protein>C/EBP beta</protein> bound to that in the <cell_line>VD3-treated HL-60 cells</cell_line> .


Furthermore , to examine the transcriptional activity of the C/EBP motif , we transfected several constructed luciferase reporter DNAs into HL-60 cells and THP-1 cells .

Furthermore , to examine the transcriptional activity of the <protein>C/EBP motif</protein> , we transfected several constructed <dna>luciferase reporter DNAs</dna> into <cell_line>HL-60 cells</cell_line> and <cell_line>THP-1 cells</cell_line> .


The luciferase activity of the C/EBP motif in HL-60 cells was increased by VD3 treatment .

The luciferase activity of the <protein>C/EBP motif</protein> in <cell_line>HL-60 cells</cell_line> was increased by VD3 treatment .


The C/EBP motif in the MRP14 gene was confirmed to function as a regulatory region in VD3-treated HL-60 cells and THP-1 cells by the assay .

The <protein>C/EBP motif</protein> in the <dna>MRP14 gene</dna> was confirmed to function as a regulatory region in <cell_line>VD3-treated HL-60 cells and THP-1 cells</cell_line> by the assay .


Since C/EBP beta was also detected in VD3-untreated HL-60 cells by immunoblotting , VD3 activated C/EBP beta to bind to the motif , probably through post-translational modification .

Since <protein>C/EBP beta</protein> was also detected in <cell_line>VD3-untreated HL-60 cells</cell_line> by immunoblotting , VD3 activated <protein>C/EBP beta</protein> to bind to the motif , probably through post-translational modification .


Patients with high-risk myelodysplastic syndrome can have polyclonal or clonal haemopoiesis in complete haematological remission .


The clonality of mature peripheral blood-derived myeloid and lymphoid cells and bone marrow haemopoietic progenitors from 18 females with myelodysplasia ( MDS ) ( five refractory anaemia , RA ; one RA with ringed sideroblasts , RARS ; three chronic myelomonocytic leukaemia , CMML ; four RA with excess of blasts , RAEB ; five RAEB in transformation , RAEB-t ) was studied by X-chromosome inactivation analysis .

The clonality of <cell_type>mature peripheral blood-derived myeloid and lymphoid cells</cell_type> and <cell_type>bone marrow haemopoietic progenitors</cell_type> from 18 females with myelodysplasia ( MDS ) ( five refractory anaemia , RA ; one RA with <cell_type>ringed sideroblasts</cell_type> , RARS ; three chronic myelomonocytic leukaemia , CMML ; four RA with excess of blasts , RAEB ; five RAEB in transformation , RAEB-t ) was studied by <dna>X-chromosome</dna> inactivation analysis .


Using the human androgen-receptor ( HUMARA ) assay , we analysed the clonal patterns of highly purified immature CD34+ 38- and committed CD34+ 38+ marrow-derived progenitors , and CD16+ 14- granulocytes , CD14+ monocytes , CD3+ T and CD19+ B lymphocytes from peripheral blood .

Using the human androgen-receptor ( HUMARA ) assay , we analysed the clonal patterns of <cell_type>highly purified immature CD34+ 38- and committed CD34+ 38+ marrow-derived progenitors</cell_type> , and <cell_type>CD16+ 14- granulocytes</cell_type> , <cell_type>CD14+ monocytes</cell_type> , <cell_type>CD3+ T and CD19+ B lymphocytes</cell_type> from peripheral blood .


In high-risk patients ( RAEB , RAEB-t ) , clonality analysis was performed before and after intensive remission-induction treatment .


All patients , except one with RA , had predominance of a single clone in their granulocytes and monocytes .

All patients , except one with RA , had predominance of a single clone in their <cell_type>granulocytes</cell_type> and <cell_type>monocytes</cell_type> .


The same clonal pattern was found in CD34+ progenitor cells .

The same clonal pattern was found in <cell_type>CD34+ progenitor cells</cell_type> .


In contrast , CD3+ T lymphocytes were polyclonal or oligoclonal in 14/18 patients .

In contrast , <cell_type>CD3+ T lymphocytes</cell_type> were polyclonal or oligoclonal in 14/18 patients .


X-chromosome inactivation patterns of CD19+ B cells were highly concordant with CD3+ T cells except for two patients ( one RA , one CMML ) with monoclonal B and polyclonal T lymphocytes , therefore suggesting a clonal mutation in a progenitor common to the myeloid and B-lymphoid lineages or the coexistence of MDS and a B-cell disorder in these particular patients .

<dna>X-chromosome</dna> inactivation patterns of <cell_type>CD19+ B cells</cell_type> were highly concordant with <cell_type>CD3+ T cells</cell_type> except for two patients ( one RA , one CMML ) with <cell_type>monoclonal B and polyclonal T lymphocytes</cell_type> , therefore suggesting a clonal mutation in a <cell_type>progenitor</cell_type> common to the <cell_type>myeloid and B-lymphoid lineages</cell_type> or the coexistence of MDS and a B-cell disorder in these particular patients .


After high-dose non-myeloablative chemotherapy , polyclonal haemopoiesis was reinstalled in the mature myeloid cells and immature and committed marrow progenitors in three of four patients achieving complete haematological remission .

After high-dose non-myeloablative chemotherapy , polyclonal haemopoiesis was reinstalled in the <cell_type>mature myeloid cells</cell_type> and immature and <cell_type>committed marrow progenitors</cell_type> in three of four patients achieving complete haematological remission .


Therefore we conclude that most haematological remissions in MDS are associated with restoration of polyclonal haemopoiesis .


Prominent sex steroid metabolism in human lymphocytes .

Prominent sex steroid metabolism in <cell_type>human lymphocytes</cell_type> .


Steroid metabolism was investigated in cultured human B-lymphoblastoid cells ( B-LCL ) , and peripheral blood T and B cells .

Steroid metabolism was investigated in <cell_line>cultured human B-lymphoblastoid cells</cell_line> ( <cell_line>B-LCL</cell_line> ) , and <cell_type>peripheral blood T and B cells</cell_type> .


Gene expression was examined by reverse-transcription polymerase chain reaction amplification ( RT-PCR ) .


Appropriate sized transcripts were detected in both cultured and fresh peripheral lymphocytes for CYP11A , CYP17 , HSD11L ( 11beta-hydroxysteroid dehydrogenase I ) , HSD17B1 ( 17beta-hydroxysteroid dehydrogenase type I ) and SRD5A1 ( 5alpha-reductase I ) .

Appropriate sized <rna>transcripts</rna> were detected in both cultured and fresh <cell_type>peripheral lymphocytes</cell_type> for <protein>CYP11A</protein> , <protein>CYP17</protein> , <protein>HSD11L</protein> ( <protein>11beta-hydroxysteroid dehydrogenase I</protein> ) , <protein>HSD17B1</protein> ( <protein>17beta-hydroxysteroid dehydrogenase type I</protein> ) and <protein>SRD5A1</protein> ( <protein>5alpha-reductase I</protein> ) .


B-LCL , but not T and B cells , expressed CYP11B .

B-LCL , but not <cell_type>T and B cells</cell_type> , expressed <protein>CYP11B</protein> .


There was minimal expression of HSD3B1 and HSD3B2 ( 3beta-hydroxysteroid dehydrogenase I and II ) in B-LCL and T cells .

There was minimal expression of <protein>HSD3B1</protein> and <protein>HSD3B2</protein> ( <protein>3beta-hydroxysteroid dehydrogenase I and II</protein> ) in <cell_line>B-LCL</cell_line> and <cell_type>T cells</cell_type> .


Transcripts for CYP19 and HSD11K were not detected .

Transcripts for <protein>CYP19</protein> and <protein>HSD11K</protein> were not detected .


Corresponding enzymatic activity was detectable only for 17-hydroxysteroid dehydrogenase and 5alpha-reductase , respectively producing testosterone and 5alpha-dihydrotestosterone .

Corresponding enzymatic activity was detectable only for <protein>17-hydroxysteroid dehydrogenase</protein> and <protein>5alpha-reductase</protein> , respectively producing testosterone and 5alpha-dihydrotestosterone .


Steroid identities were confirmed by gas chromatography/mass spectrometry ( GC/MS ) .


One metabolite thought to be deoxycorticosterone was identified by GC/MS as 6alpha-hydroxypregnanolone .


It was concluded that sex hormone metabolism , including androgen synthesis , occurs in lymphocytes , and may modulate immune response .


Human white blood cells and hair follicles are good sources of mRNA for the pterin carbinolamine dehydratase/dimerization cofactor of HNF1 for mutation detection .

<cell_type>Human white blood cells</cell_type> and hair follicles are good sources of <rna>mRNA</rna> for the <protein>pterin carbinolamine dehydratase/dimerization cofactor</protein> of <protein>HNF1</protein> for mutation detection .


Pterin carbinolamine dehydratase/dimerization cofactor of HNF1 ( PCD/DCoH ) is a protein that has a dual function .

<protein>Pterin carbinolamine dehydratase/dimerization cofactor</protein> of <protein>HNF1</protein> ( <protein>PCD/DCoH</protein> ) is a protein that has a dual function .


It is a pterin 4alpha-carbinolamine dehydratase that is involved in the regeneration of the cofactor tetrahydrobiopterin during the phenylalanine hydroxylase- catalyzed hydroxylation of phenylalanine .

It is a <protein>pterin 4alpha-carbinolamine dehydratase</protein> that is involved in the regeneration of the <protein>cofactor tetrahydrobiopterin</protein> during the phenylalanine hydroxylase- catalyzed hydroxylation of phenylalanine .


In addition , it is the dimerization cofactor of HNF1 that is able to activate the transcriptional activity of HNF1 .

In addition , it is the dimerization cofactor of <protein>HNF1</protein> that is able to activate the transcriptional activity of <protein>HNF1</protein> .


Deficiencies in the gene for this dual functional protein result in hyperphenylalaninemia .

Deficiencies in the gene for this <protein>dual functional protein</protein> result in hyperphenylalaninemia .


Here we report for the first time that the PCD/DCoH mRNA is present in human white blood cells and hair follicles .

Here we report for the first time that the <rna>PCD/DCoH mRNA</rna> is present in <cell_type>human white blood cells</cell_type> and hair follicles .


Taking advantage of this finding , a sensitive , rapid and convenient method for screening mutations occurring in the coding region of this gene has been described .


Copyright 1998 Academic Press .


Biochemical characterization of the NF-Y transcription factor complex during B lymphocyte development .

Biochemical characterization of the <protein>NF-Y transcription factor complex</protein> during B lymphocyte development .


The transcription factor , NF-Y , plays a critical role in tissue-specific major histocompatibility complex class II gene transcription .

The <protein>transcription factor</protein> , <protein>NF-Y</protein> , plays a critical role in tissue-specific <dna>major histocompatibility complex class II gene</dna> transcription .


In this report the biochemical properties of the heterotrimeric NF-Y complex have been characterized during stage-specific B-cell development , and in several class II- mutant B-cell lines , which represent distinct bare lymphocyte syndrome class II genetic complementation groups .

In this report the biochemical properties of the <protein>heterotrimeric NF-Y complex</protein> have been characterized during stage-specific B-cell development , and in several <cell_line>class II- mutant B-cell lines</cell_line> , which represent distinct bare lymphocyte syndrome class II genetic complementation groups .


The NF-Y complex derived from class II+ mature B-cells bound with high affinity to anion exchangers , and eluted as an intact trimeric complex , whereas , NF-Y derived from class II- plasma B-cells , and from bare lymphocyte syndrome group II cell lines , RJ2.2.5 and RM3 , dissociated into discrete NF-YA and NF-YB : C subunit fractions .

The <protein>NF-Y complex</protein> derived from <cell_type>class II+ mature B-cells</cell_type> bound with high affinity to <protein>anion exchangers</protein> , and eluted as an intact <protein>trimeric complex</protein> , whereas , <protein>NF-Y</protein> derived from <cell_type>class II- plasma B-cells</cell_type> , and from <cell_line>bare lymphocyte syndrome group II cell lines</cell_line> , <cell_line>RJ2.2.5</cell_line> and <cell_line>RM3</cell_line> , dissociated into discrete <protein>NF-YA</protein> and <protein>NF-YB : C</protein> <protein>subunit fractions</protein> .


Recombination of the MPC11 plasma B-cell derived NF-Y A : B : C complex with the low molecular mass protein fraction , NF-Y-associated factors ( YAFs ) , derived from mature A20 B-cell nuclei , conferred high affinity anion exchange binding to NF-Y as an intact trimeric complex .

Recombination of the <protein>MPC11 plasma B-cell derived NF-Y A : B : C complex</protein> with the low molecular mass protein fraction , <protein>NF-Y-associated factors</protein> ( <protein>YAFs</protein> ) , derived from mature A20 B-cell nuclei , conferred high affinity anion exchange binding to <protein>NF-Y</protein> as an <protein>intact trimeric complex</protein> .


Recombination of the native NF-YA : B : C complex with the transcriptional cofactor , PC4 , likewise conferred high affinity NF-Y binding to anion exchangers , and stabilized NF-Y interaction with CCAAT-box DNA motifs in vitro .

Recombination of the <protein>native NF-YA : B : C complex</protein> with the <protein>transcriptional cofactor</protein> , <protein>PC4</protein> , likewise conferred <protein>high affinity NF-Y</protein> binding to <protein>anion exchangers</protein> , and stabilized <protein>NF-Y</protein> interaction with <dna>CCAAT-box DNA motifs</dna> in vitro .


Interaction between PC4 and NF-Y was mapped to the C-terminal region of PC4 , and the subunit interaction subdomain of the highly conserved DNA binding-subunit interaction domain ( DBD ) of NF-YA .

Interaction between <protein>PC4</protein> and <protein>NF-Y</protein> was mapped to the <protein>C-terminal region</protein> of <protein>PC4</protein> , and the <protein>subunit interaction subdomain</protein> of the <protein>highly conserved DNA binding-subunit interaction domain</protein> ( <protein>DBD</protein> ) of <protein>NF-YA</protein> .


These results suggest that in class II+ mature B-cells NF-Y is associated with the protein cofactor , PC4 , which may play an important role in NF-Y-mediated transcriptional control of class II genes .

These results suggest that in <cell_type>class II+ mature B-cells</cell_type> <protein>NF-Y</protein> is associated with the protein cofactor , <protein>PC4</protein> , which may play an important role in NF-Y-mediated transcriptional control of <dna>class II genes</dna> .


Arrest of B lymphocyte terminal differentiation by CD40 signaling : mechanism for lack of antibody-secreting cells in germinal centers .

Arrest of B lymphocyte terminal differentiation by CD40 signaling : mechanism for lack of <cell_type>antibody-secreting cells</cell_type> in germinal centers .


Despite extensive research , the role of CD40 signaling in B cell terminal differentiation remains controversial .

Despite extensive research , the role of <protein>CD40</protein> signaling in B cell terminal differentiation remains controversial .


Here we show that CD40 engagement arrests B cell differentiation prior to plasma cell formation .

Here we show that <protein>CD40</protein> engagement arrests B cell differentiation prior to plasma cell formation .


This arrest is manifested at a molecular level as a reduction in mRNA levels of secretory immunoglobulin gene products such as mu ( s ) and J chain as well as the loss of the transcriptional regulator BLIMP-1 .

This arrest is manifested at a molecular level as a reduction in mRNA levels of secretory immunoglobulin gene products such as mu ( s ) and J chain as well as the loss of the <protein>transcriptional regulator</protein> <protein>BLIMP-1</protein> .


Furthermore , the inhibition of B cell differentiation by CD40 engagement could not be overcome by either mitogens or cytokines , but could be reversed by antibodies that interfere with the CD40 / gp39 interaction .

Furthermore , the inhibition of B cell differentiation by <protein>CD40</protein> engagement could not be overcome by either <protein>mitogens</protein> or <protein>cytokines</protein> , but could be reversed by antibodies that interfere with the <protein>CD40</protein> / <protein>gp39</protein> interaction .


These data suggest that secretory immunoglobulin is not produced by B cells that are actively engaged by gp39-expressing T cells .

These data suggest that secretory immunoglobulin is not produced by <cell_type>B cells</cell_type> that are actively engaged by <cell_type>gp39-expressing T cells</cell_type> .


A positively charged alpha-lipoic acid analogue with increased cellular uptake and more potent immunomodulatory activity .


alpha-Lipoic acid ( LA ) is taken up by cells and reduced to its potent dithiol form , dihydrolipoate ( DHLA ) , much of which is rapidly effluxed out from cells .


To improve retention in cells , the LA molecule was modified to confer a positive charge at physiological pH .


N , N-dimethyl , N'-2-amidoethyl-lipoate was synthesized .


The protonated form of the new molecule is referred to as LA-Plus .


The uptake of LA-Plus by human Wurzburg T cells was higher compared to that of LA .

The uptake of LA-Plus by <cell_type>human Wurzburg T cells</cell_type> was higher compared to that of LA .


Several-fold higher amounts of DHLA-Plus , the corresponding reduced form of LA-Plus , were detected in LA-Plus treated cells compared to the amount of DHLA found in cells treated with LA .


At 100 microM , LA did not but LA-Plus inhibited H2O2 induced NF-kappaB activation and NF-kappaB directed IL-2 receptor expression .

At 100 microM , LA did not but LA-Plus inhibited H2O2 induced <protein>NF-kappaB</protein> activation and <protein>NF-kappaB</protein> directed <protein>IL-2 receptor</protein> expression .


Both LA and LA-Plus synergised with selenium in inhibiting H2O2 induced NF-kappaB activation .

Both LA and LA-Plus synergised with selenium in inhibiting H2O2 induced <protein>NF-kappaB</protein> activation .


At 150 microM LA-Plus , but not LA , inhibited TNFalpha induced NF-kappaB activation .

At 150 microM LA-Plus , but not LA , inhibited <protein>TNFalpha</protein> induced <protein>NF-kappaB</protein> activation .


At 5 microM LA-Plus , but not LA , protected against both spontaneous and etoposide induced apoptosis in rat thymocytes .

At 5 microM LA-Plus , but not LA , protected against both spontaneous and etoposide induced apoptosis in <cell_type>rat thymocytes</cell_type> .


LA-Plus is thus an improved form of LA with increased therapeutic potential .


Copyright 1998 Academic Press .


Carrier identification in X-linked immunodeficiency diseases .


OBJECTIVE : Carrier identification in X-linked immunodeficiency disorders can be based on the demonstration of non-random X inactivation ( NRXI ) in affected blood cell lineages when growth is impaired in cells expressing the abnormal gene .

OBJECTIVE : Carrier identification in X-linked immunodeficiency disorders can be based on the demonstration of non-random X inactivation ( NRXI ) in <cell_type>affected blood cell lineages</cell_type> when growth is impaired in cells expressing the <dna>abnormal gene</dna> .


We examined the utility of seeking evidence of NRXI to test the carrier status of women in families affected by X-linked severe combined immunodeficiency ( XSCID ) and X-linked hypogammaglobulinaemia ( XLH ) , to identify as carriers the mothers of boys with SCID or hypogammaglobulinaemia whose phenotype suggested X-linkage and to infer X-linkage in boys with SCID or hypogammaglobulinaemia whose disease was not clearly X-linked on the basis either of family history or clinical and immunological characteristics .


METHODOLOGY : A polymerase chain reaction-based method was used to amplify a polymorphic CAG repeat in the first exon of the androgen receptor gene after selective digestion of the active X chromosome with a methylation-sensitive enzyme , HpaII to distinguish between the paternal and maternal alleles and to identify their methylation status .

METHODOLOGY : A polymerase chain reaction-based method was used to amplify a polymorphic <dna>CAG repeat</dna> in the <dna>first exon</dna> of the <dna>androgen receptor gene</dna> after selective digestion of the <dna>active X chromosome</dna> with a <protein>methylation-sensitive enzyme</protein> , <protein>HpaII</protein> to distinguish between the <dna>paternal and maternal alleles</dna> and to identify their methylation status .


RESULTS : Heterozygosity was found in 24 of 31 female subjects ( 77 % ) .


As anticipated , NRXI could be demonstrated in all lymphoid cells studied from obligate carriers of XSCID and an obligate carrier of XLH but not on a carrier of X-linked immunodeficiency with hyper-IgM .

As anticipated , NRXI could be demonstrated in all <cell_type>lymphoid cells</cell_type> studied from obligate carriers of XSCID and an obligate carrier of XLH but not on a carrier of X-linked immunodeficiency with <protein>hyper-IgM</protein> .


The finding of NRXI in the mother of a boy with a SCID variant showed her to be a carrier of XSCID and establishes that her son has XSCID , not otherwise evident from available data .


CONCLUSIONS : This PCR assay provides a rapid method for carrier detection of X-linked immunodeficiencies , and has allowed us to expand the phenotype of XSCID


Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-kB-dependent fashion .


We addressed the role of hyperglycemia in leukocyte-endothelium interaction under flow conditions by exposing human umbilical vein endothelial cells for 24 h to normal ( 5 mM ) , high concentration of glucose ( 30 mM ) , advanced glycosylation end product-albumin ( 100 microg/ml ) , or hyperglycemic ( 174-316 mg/dl ) sera from patients with diabetes and abnormal hemoglobin A1c ( 8.1+/-1.4 % ) .

We addressed the role of hyperglycemia in leukocyte-endothelium interaction under flow conditions by exposing <cell_type>human umbilical vein endothelial cells</cell_type> for 24 h to normal ( 5 mM ) , high concentration of glucose ( 30 mM ) , advanced glycosylation end <protein>product-albumin</protein> ( 100 microg/ml ) , or hyperglycemic ( 174-316 mg/dl ) sera from patients with diabetes and abnormal hemoglobin A1c ( 8.1+/-1.4 % ) .


At the end of incubation endothelial cells were perfused with total leukocyte suspension in a parallel plate flow chamber under laminar flow ( 1.5 dyn/cm2 ) .

At the end of incubation <cell_type>endothelial cells</cell_type> were perfused with total leukocyte suspension in a parallel plate flow chamber under laminar flow ( 1.5 dyn/cm2 ) .


Rolling and adherent cells were evaluated by digital image processing .

Rolling and <cell_type>adherent cells</cell_type> were evaluated by digital image processing .


Results showed that 30 mM glucose significantly ( P < 0.01 ) increased the number of adherent leukocytes to endothelial cells in respect to control ( 5 mM glucose ; 151+/-19 versus 33+/-8 cells/mm2 ) .

Results showed that 30 mM glucose significantly ( P < 0.01 ) increased the number of <cell_type>adherent leukocytes</cell_type> to <cell_type>endothelial cells</cell_type> in respect to control ( 5 mM glucose ; 151+/-19 versus 33+/-8 cells/mm2 ) .


A similar response was induced by endothelial stimulation with IL-1beta , here used as positive control ( 195+/-20 cells/mm2 ) .

A similar response was induced by endothelial stimulation with <protein>IL-1beta</protein> , here used as positive control ( 195+/-20 cells/mm2 ) .


The number of rolling cells on endothelial surface was not affected by high glucose level .

The number of <cell_type>rolling cells</cell_type> on endothelial surface was not affected by high glucose level .


Stable adhesion of leukocytes to glucose-treated as well as to IL-1beta-stimulated endothelial cells was preceded by short interaction of leukocytes with the endothelial surface .

Stable adhesion of <cell_type>leukocytes</cell_type> to glucose-treated as well as to <cell_type>IL-1beta-stimulated endothelial cells</cell_type> was preceded by short interaction of <cell_type>leukocytes</cell_type> with the endothelial surface .


The distance travelled by leukocytes before arrest on 30 mM glucose , or on IL-1beta-treated endothelial cells , was significantly ( P < 0.01 ) higher than that observed for leukocytes adhering on control endothelium ( 30 mM glucose : 76.7+/-3.5 ; IL1beta : 69.7+/-4 versus 5 mM glucose : 21.5+/-5 microm ) .

The distance travelled by <cell_type>leukocytes</cell_type> before arrest on 30 mM glucose , or on <cell_type>IL-1beta-treated endothelial cells</cell_type> , was significantly ( P < 0.01 ) higher than that observed for <cell_type>leukocytes</cell_type> adhering on control endothelium ( 30 mM glucose : 76.7+/-3.5 ; IL1beta : 69.7+/-4 versus 5 mM glucose : 21.5+/-5 microm ) .


Functional blocking of E-selectin , intercellular cell adhesion molecule-1 , and vascular cell adhesion molecule-1 on endothelial cells with the corresponding mouse mAb significantly inhibited glucose-induced increase in leukocyte adhesion ( 67+/-16 , 83+/-12 , 62+/-8 versus 144+/-21 cells/ mm2 ) .

Functional blocking of <protein>E-selectin</protein> , <protein>intercellular cell adhesion molecule-1</protein> , and <protein>vascular cell adhesion molecule-1</protein> on <cell_type>endothelial cells</cell_type> with the corresponding <protein>mouse mAb</protein> significantly inhibited glucose-induced increase in leukocyte adhesion ( 67+/-16 , 83+/-12 , 62+/-8 versus 144+/-21 cells/ mm2 ) .


Confocal fluorescence microscopy studies showed that 30 mM glucose induced an increase in endothelial surface expression of E-selectin , intercellular cell adhesion molecule-1 , and vascular cell adhesion molecule-1 .

Confocal fluorescence microscopy studies showed that 30 mM glucose induced an increase in endothelial surface expression of <protein>E-selectin</protein> , <protein>intercellular cell adhesion molecule-1</protein> , and <protein>vascular cell adhesion molecule-1</protein> .


Electrophoretic mobility shift assay of nuclear extracts of human umbilical vein endothelial cells ( HUVEC ) exposed for 1 h to 30 mM glucose revealed an intense NF-kB activation .

Electrophoretic mobility shift assay of nuclear extracts of <cell_type>human umbilical vein endothelial cells</cell_type> ( HUVEC ) exposed for 1 h to 30 mM glucose revealed an intense <protein>NF-kB</protein> activation .


Treatment of HUVEC exposed to high glucose with the NF-kB inhibitors pyrrolidinedithiocarbamate ( 100 microM ) and tosyl-phe-chloromethylketone ( 25 microM ) significantly reduced ( P < 0.05 ) leukocyte adhesion in respect to HUVEC treated with glucose alone .

Treatment of HUVEC exposed to high glucose with the <protein>NF-kB inhibitors</protein> pyrrolidinedithiocarbamate ( 100 microM ) and tosyl-phe-chloromethylketone ( 25 microM ) significantly reduced ( P < 0.05 ) leukocyte adhesion in respect to HUVEC treated with glucose alone .


A significant ( P < 0.01 ) inhibitory effect on glucose-induced leukocyte adhesion was observed after blocking protein kinase C activity with staurosporine ( 5 nM ) .

A significant ( P < 0.01 ) inhibitory effect on glucose-induced leukocyte adhesion was observed after blocking <protein>protein kinase C</protein> activity with staurosporine ( 5 nM ) .


When HUVEC were treated with specific antisense oligodesoxynucleotides against PKCalpha and PKCepsilon isoforms before the addition of 30 mM glucose , a significant ( P < 0.05 ) reduction in the adhesion was also seen .

When HUVEC were treated with specific antisense oligodesoxynucleotides against <protein>PKCalpha and PKCepsilon isoforms</protein> before the addition of 30 mM glucose , a significant ( P < 0.05 ) reduction in the adhesion was also seen .


Advanced glycosylation end product-albumin significantly increased the number of adhering leukocytes in respect to native albumin used as control ( 110+/-16 versus 66+/-7 , P < 0.01 ) .

Advanced glycosylation end <protein>product-albumin</protein> significantly increased the number of <cell_type>adhering leukocytes</cell_type> in respect to <protein>native albumin</protein> used as control ( 110+/-16 versus 66+/-7 , P < 0.01 ) .


Sera from diabetic patients significantly ( P < 0.01 ) enhanced leukocyte adhesion as compared with controls , despite normal levels of IL-1beta and TNFalpha in these sera .

Sera from diabetic patients significantly ( P < 0.01 ) enhanced leukocyte adhesion as compared with controls , despite normal levels of <protein>IL-1beta</protein> and <protein>TNFalpha</protein> in these sera .


These data indicate that high glucose concentration and hyperglycemia promote leukocyte adhesion to the endothelium through upregulation of cell surface expression of adhesive proteins , possibly depending on NF-kB activation .

These data indicate that high glucose concentration and hyperglycemia promote leukocyte adhesion to the endothelium through upregulation of cell surface expression of adhesive proteins , possibly depending on <protein>NF-kB</protein> activation .


Ikaros in hemopoietic lineage determination and homeostasis .

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


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


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

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


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

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


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

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


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

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


Induction of early B cell factor ( EBF ) and multiple B lineage genes by the basic helix-loop-helix transcription factor E12 .

Induction of <protein>early B cell factor</protein> ( <protein>EBF</protein> ) and <dna>multiple B lineage genes</dna> by the <protein>basic helix-loop-helix transcription factor</protein> <protein>E12</protein> .


The transcription factors encoded by the E2A and early B cell factor ( EBF ) genes are required for the proper development of B lymphocytes .

The <protein>transcription factors</protein> encoded by the <protein>E2A</protein> and <protein>early B cell factor</protein> ( <protein>EBF</protein> ) genes are required for the proper development of <cell_type>B lymphocytes</cell_type> .


However , the absence of B lineage cells in E2A- and EBF-deficient mice has made it difficult to determine the function or relationship between these proteins .

However , the absence of <cell_type>B lineage cells</cell_type> in E2A- and EBF-deficient mice has made it difficult to determine the function or relationship between these proteins .


We report the identification of a novel model system in which the role of E2A and EBF in the regulation of multiple B lineage traits can be studied .

We report the identification of a novel model system in which the role of <protein>E2A</protein> and <protein>EBF</protein> in the regulation of multiple B lineage traits can be studied .


We found that the conversion of 70Z/3 pre-B lymphocytes to cells with a macrophage-like phenotype is associated with the loss of E2A and EBF .

We found that the conversion of <cell_line>70Z/3 pre-B lymphocytes</cell_line> to cells with a macrophage-like phenotype is associated with the loss of <protein>E2A</protein> and <protein>EBF</protein> .


Moreover , we show that ectopic expression of the E2A protein E12 in this macrophage line results in the induction of many B lineage genes , including EBF , IL7Ralpha , lambda5 , and Rag-1 , and the ability to induce kappa light chain in response to mitogen .

Moreover , we show that ectopic expression of the <protein>E2A</protein> protein <protein>E12</protein> in this <cell_line>macrophage line</cell_line> results in the induction of <dna>many B lineage genes</dna> , including <protein>EBF</protein> , <protein>IL7Ralpha</protein> , <protein>lambda5</protein> , and Rag-1 , and the ability to induce <protein>kappa light chain</protein> in response to mitogen .


Activation of EBF may be one of the critical functions of E12 in regulating the B lineage phenotype since expression of EBF alone leads to the activation of a subset of E12 -inducible traits .

Activation of <protein>EBF</protein> may be one of the critical functions of <protein>E12</protein> in regulating the B lineage phenotype since expression of <protein>EBF</protein> alone leads to the activation of a subset of <protein>E12</protein> -inducible traits .


Our data demonstrate that , in the context of this macrophage line , E12 induces expression of EBF and together these transcription factors coordinately regulate numerous B lineage-associated genes .

Our data demonstrate that , in the context of this <cell_line>macrophage line</cell_line> , <protein>E12</protein> induces expression of <protein>EBF</protein> and together these <protein>transcription factors</protein> coordinately regulate numerous <dna>B lineage-associated genes</dna> .


Activation-induced down-regulation of retinoid receptor RXRalpha expression in human T lymphocytes .

Activation-induced down-regulation of <protein>retinoid receptor RXRalpha</protein> expression in <cell_type>human T lymphocytes</cell_type> .


Role of cell cycle regulation .


A 5.4-kilobase mRNA , the expression of which is down-regulated after treatment of human peripheral blood mononuclear cells ( PBMCs ) with various T cell-activating agents , was isolated using an mRNA differential display method .

A <rna>5.4-kilobase mRNA</rna> , the expression of which is down-regulated after treatment of <cell_type>human peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMCs</cell_type> ) with various T cell-activating agents , was isolated using an mRNA differential display method .


Nucleotide sequence analysis identified the 5 ' end of this RNA as human retinoid receptor RXRalpha mRNA .

Nucleotide sequence analysis identified the <rna>5 ' end</rna> of this <rna>RNA</rna> as <rna>human retinoid receptor RXRalpha mRNA</rna> .


Here , we report the nucleotide sequence of 3.6 kilobases of this RNA , which represents the 3 ' end of RXRalpha mRNA , the sequence of which has not been previously described .

Here , we report the nucleotide sequence of <dna>3.6 kilobases</dna> of this RNA , which represents the <rna>3 ' end</rna> of <rna>RXRalpha mRNA</rna> , the sequence of which has not been previously described .


Activated PBMCs also expressed lower levels of RXRalpha protein , and a DNA binding assay showed that the activation-induced loss of RXRalpha mRNA and protein expression correlated with the loss of DNA binding activity of this protein .

Activated <cell_type>PBMCs</cell_type> also expressed lower levels of <protein>RXRalpha</protein> protein , and a DNA binding assay showed that the activation-induced loss of <rna>RXRalpha mRNA</rna> and protein expression correlated with the loss of DNA binding activity of this protein .


We present evidence that the transition from G0/G1 to S phase of the cell cycle results in the down-regulation of RXRalpha expression and that cell cycle inhibitors , which block the cells in G1 phase , prevent this down-regulation .

We present evidence that the transition from G0/G1 to S phase of the cell cycle results in the down-regulation of <protein>RXRalpha</protein> expression and that cell cycle inhibitors , which block the cells in G1 phase , prevent this down-regulation .


The decrease in the levels of RXRalpha mRNA was found to be regulated at the post-transcriptional level and involved new protein synthesis .

The decrease in the levels of <rna>RXRalpha mRNA</rna> was found to be regulated at the post-transcriptional level and involved new protein synthesis .


These observations indicate that the levels of RXRalpha expression in T lymphocytes are coupled to cell cycle progression , and there is tight regulatory control of RXRalpha expression during the transition from G0/G1 to S phase of the cell cycle .

These observations indicate that the levels of <protein>RXRalpha</protein> expression in T lymphocytes are coupled to cell cycle progression , and there is tight regulatory control of <protein>RXRalpha</protein> expression during the transition from G0/G1 to S phase of the cell cycle .


Epidemiology and pathogenesis of AIDS-related lymphomas .


Among patients with congenital and acquired immunodeficiencies , non-Hodgkin 's lymphoma ( NHLs ) are the most common tumors of the immune system .


In the setting of human immunodeficiency virus ( HIV ) infection , as many as 10 % to 20 % of people ultimately developed NHLs .


These tumors are clinically aggressive , frequently involve extranodal sites , and often exhibit unique features that distinguish them from NHL arising in individuals with other forms of immunosuppression .


Important in the development of HIV-associated NHL are cytokines and other factors that induce B-cell proliferation and increase the likelihood of mutations of c-myc , bcl-6 , and other tumor-suppressor genes with carcinogenic potential .

Important in the development of HIV-associated NHL are <protein>cytokines</protein> and other factors that induce B-cell proliferation and increase the likelihood of mutations of <dna>c-myc</dna> , <dna>bcl-6</dna> , and other <dna>tumor-suppressor genes</dna> with carcinogenic potential .


Specific forms of HIV-associated NHL are linked to expression of Epstein-Barr virus ( EBV ) -latent proteins ; the newly described DNA virus , Karposi 's sarcoma-associated herpesvirus/human herpesvirus-8 ( KSHV/HHV-8 ) ; and perhaps HIV .

Specific forms of HIV-associated NHL are linked to expression of <protein>Epstein-Barr virus ( EBV ) -latent proteins</protein> ; the newly described DNA virus , Karposi 's sarcoma-associated herpesvirus/human herpesvirus-8 ( KSHV/HHV-8 ) ; and perhaps HIV .


Elucidation of the factors that contribute to the high incidence of NHL among patients infected with HIV provides insights into important elements of lymphomagenesis .


Matrix metalloproteinase expression in human breast cancer : an immunohistochemical study including correlation with cathepsin D , type IV collagen , laminin , fibronectin , EGFR , c-erbB-2 oncoprotein , p53 , steroid receptors status and proliferative indices .

<protein>Matrix metalloproteinase</protein> expression in human breast cancer : an immunohistochemical study including correlation with <protein>cathepsin D</protein> , <protein>type IV collagen</protein> , <protein>laminin</protein> , <protein>fibronectin</protein> , <protein>EGFR</protein> , <protein>c-erbB-2 oncoprotein</protein> , <protein>p53</protein> , steroid receptors status and proliferative indices .


Matrix metalloproteinase s ( MMPs ) are a group of enzymes thought to be responsible for both normal connective tissue matrix remodelling and accelerated breakdown associated with tumour development .

<protein>Matrix metalloproteinase</protein> s ( <protein>MMPs</protein> ) are a group of enzymes thought to be responsible for both normal connective tissue matrix remodelling and accelerated breakdown associated with tumour development .


The current study aimed to investigate the immunohistochemical expression of matrix metalloproteinase 3 ( MMP-3 , stromelysin-1 ) in correlation with the expression of Basement Membrane ( BM ) antigen ( type IV collagen , laminin ) , fibronectin , cathepsin D , p53 , c-erbB-2 , proliferative activity ( Ki-67 , PCNA ) , steroid receptor content as well as to the other conventional clinicopathological parameters in breast cancer .

The current study aimed to investigate the immunohistochemical expression of <protein>matrix metalloproteinase 3</protein> ( <protein>MMP-3</protein> , <protein>stromelysin-1</protein> ) in correlation with the expression of <protein>Basement Membrane ( BM ) antigen</protein> ( <protein>type IV collagen</protein> , <protein>laminin</protein> ) , <protein>fibronectin</protein> , <protein>cathepsin D</protein> , <protein>p53</protein> , <protein>c-erbB-2</protein> , proliferative activity ( <protein>Ki-67</protein> , <protein>PCNA</protein> ) , steroid receptor content as well as to the other conventional clinicopathological parameters in breast cancer .


This study was performed on a series of frozen and paraffin sections from 84 breast cancer specimens by immunohistochemistry using the monoclonal antibody MMP-3 ( Ab-1 ) .

This study was performed on a series of frozen and paraffin sections from 84 breast cancer specimens by immunohistochemistry using the <protein>monoclonal antibody MMP-3</protein> ( <protein>Ab-1</protein> ) .


Stromelysin-1 ( ST1 ) was observed in about 10 % of epithelial cells in the control groups ( cases of fibrocystic and benign proliferative breast disease ) , while expression ( > 10 % of expression ) was detected in 89.7 % of tumours .

<protein>Stromelysin-1</protein> ( <protein>ST1</protein> ) was observed in about 10 % of <cell_type>epithelial cells</cell_type> in the control groups ( cases of fibrocystic and benign proliferative breast disease ) , while expression ( > 10 % of expression ) was detected in 89.7 % of tumours .


The expression of ST1 in carcinoma cells was strongly associated with its presence in the stroma ( p < 0.001 ) .

The expression of <protein>ST1</protein> in carcinoma cells was strongly associated with its presence in the stroma ( p < 0.001 ) .


A significantly positive correlation was found between ST1 expression , and p53 tumour suppressor gene product ( p = 0.004 ) , and a relationship with c-erbB-2 protein and progesterone receptor status was also indicated .

A significantly positive correlation was found between <protein>ST1</protein> expression , and <protein>p53</protein> tumour suppressor gene product ( p = 0.004 ) , and a relationship with <protein>c-erbB-2</protein> protein and progesterone receptor status was also indicated .


These findings suggest that ST1 expression in breast cancer tissue is irrespective of the expression of the extracellular matrix component , the proteolytic enzyme cathepsin D and the growth fraction of the tumour , and that it could be a potential new prognostic marker in breast cancer .

These findings suggest that <protein>ST1</protein> expression in breast cancer tissue is irrespective of the expression of the extracellular matrix component , the <protein>proteolytic enzyme</protein> <protein>cathepsin D</protein> and the growth fraction of the tumour , and that it could be a potential new prognostic marker in breast cancer .


Use of transfected liver cells to evaluate potential mechanisms of alcohol-induced liver injury [ see comments ]

Use of <cell_line>transfected liver cells</cell_line> to evaluate potential mechanisms of alcohol-induced liver injury [ see comments ]


There is increased activity of the proinflammatory cytokine , tumor necrosis factor ( TNF ) in alcoholic liver disease ( ALD ) .

There is increased activity of the <protein>proinflammatory cytokine</protein> , <protein>tumor necrosis factor</protein> ( <protein>TNF</protein> ) in alcoholic liver disease ( ALD ) .


Hepatic neutrophil infiltration is a principal injurious manifestation of ALD .


TNF can induce cellular oxidative injury directly , and indirectly by inducing neutrophil chemotactic factor ( IL-8 ) production by hepatocytes .

<protein>TNF</protein> can induce cellular oxidative injury directly , and indirectly by inducing neutrophil chemotactic factor ( <protein>IL-8</protein> ) production by hepatocytes .


IL-8 activates and chemotactically attracts neutrophils to the liver where they release oxidizing substances .

<protein>IL-8</protein> activates and chemotactically attracts neutrophils to the liver where they release oxidizing substances .


Patients with ALD also have decreased protective factors for cellular oxidative injury .

Patients with ALD also have decreased <protein>protective factors</protein> for cellular oxidative injury .


Manganous superoxide dismutase ( MnSOD ) is an antioxidant protective factor .

<protein>Manganous superoxide dismutase</protein> ( <protein>MnSOD</protein> ) is an <protein>antioxidant protective factor</protein> .


The objectives of these studies were to investigate mechanisms for induction of an injurious factor ( IL-8 ) and a protective factor ( MnSOD ) in the HepG2 human hepatoma cell line .

The objectives of these studies were to investigate mechanisms for induction of an <protein>injurious factor</protein> ( <protein>IL-8</protein> ) and a <protein>protective factor</protein> ( <protein>MnSOD</protein> ) in the <cell_line>HepG2 human hepatoma cell line</cell_line> .


In the first set of experiments , IL-8 gene reporter constructs were used to transiently transfect a derivative ( MVh2E1-9 ) of the HepG2 cell line which expresses P-4502E1 and metabolizes ethanol .

In the first set of experiments , <dna>IL-8 gene reporter constructs</dna> were used to transiently transfect a derivative ( <cell_line>MVh2E1-9</cell_line> ) of the <cell_line>HepG2 cell line</cell_line> which expresses <protein>P-4502E1</protein> and metabolizes ethanol .


Inactivation of the NF-kappaB and 3'NF-IL-6 DNA binding sites decreased IL-8 gene transcriptional activation in response to TNF while inactivation of the 5'NF-IL-6 binding site increased IL-8 gene transcriptional activity in response to TNF .

Inactivation of the <dna>NF-kappaB and 3'NF-IL-6 DNA binding sites</dna> decreased <dna>IL-8 gene</dna> transcriptional activation in response to <protein>TNF</protein> while inactivation of the <dna>5'NF-IL-6 binding site</dna> increased <dna>IL-8 gene</dna> transcriptional activity in response to <protein>TNF</protein> .


This system may be useful to assess the effects of ethanol on TNF -induced hepatocyte IL-8 production .

This system may be useful to assess the effects of ethanol on <protein>TNF</protein> -induced hepatocyte <protein>IL-8</protein> production .


In the second set of experiments , HepG2 cells were cultured in 25 to 100 mmol concentrations of ethanol .

In the second set of experiments , <cell_line>HepG2 cells</cell_line> were cultured in 25 to 100 mmol concentrations of ethanol .


Both TNF and ethanol increased HepG2 cell MnSOD activity in short-term ( 72 hr ) cultures with ethanol .

Both <protein>TNF</protein> and ethanol increased <cell_line>HepG2 cell</cell_line> <protein>MnSOD</protein> activity in short-term ( 72 hr ) cultures with ethanol .


However , after long-term ( 10 weeks ) culture with ethanol , there was no induction of MnSOD by ethanol and there was a diminished induction of MnSOD in response to TNF .

However , after long-term ( 10 weeks ) culture with ethanol , there was no induction of <protein>MnSOD</protein> by ethanol and there was a diminished induction of <protein>MnSOD</protein> in response to <protein>TNF</protein> .


Further studies are needed to assess the effect of this diminished induction of MnSOD with chronic ethanol culture on HepG2 cell susceptibility to TNF cytotoxicity .

Further studies are needed to assess the effect of this diminished induction of <protein>MnSOD</protein> with chronic ethanol culture on <cell_line>HepG2 cell</cell_line> susceptibility to <cell_line>TNF cytotoxicity</cell_line> .


We conclude that transfected liver cell lines can be used to evaluate mechanisms for increased injurious factors and decreased protective factors in alcoholic liver injury .

We conclude that transfected <cell_line>liver cell lines</cell_line> can be used to evaluate mechanisms for increased <protein>injurious factors</protein> and decreased <protein>protective factors</protein> in alcoholic liver injury .


Tissue factor transcription driven by Egr-1 is a critical mechanism of murine pulmonary fibrin deposition in hypoxia .

Tissue factor transcription driven by <protein>Egr-1</protein> is a critical mechanism of <protein>murine pulmonary fibrin</protein> deposition in hypoxia .


Local hypoxemia and stasis trigger thrombosis .


We have demonstrated previously that in a murine model of normobaric hypoxia pulmonary fibrin deposition is a result of expression of tissue factor , especially in oxygen-deprived mononuclear phagocytes ( MPs ) .

We have demonstrated previously that in a murine model of normobaric hypoxia pulmonary <protein>fibrin</protein> deposition is a result of expression of <protein>tissue factor</protein> , especially in <protein>oxygen-deprived mononuclear phagocytes</protein> ( <protein>MPs</protein> ) .


We now show that transcription factor early-growth-response gene product ( Egr-1 ) is rapidly activated in hypoxia , both in vitro and in vivo , and is responsible for transcription and expression of tissue factor in hypoxic lung .

We now show that <protein>transcription factor early-growth-response gene product</protein> ( <protein>Egr-1</protein> ) is rapidly activated in hypoxia , both in vitro and in vivo , and is responsible for transcription and expression of <protein>tissue factor</protein> in hypoxic lung .


MPs and HeLa cells subjected to hypoxia ( pO2 approximately 13 torr ) had increased levels of tissue factor transcripts ( approximately 18-fold ) and an increased rate of transcription ( approximately 15-fold ) , based on nuclear run-on analysis .

<protein>MPs</protein> and <cell_line>HeLa cells</cell_line> subjected to hypoxia ( pO2 approximately 13 torr ) had increased levels of <rna>tissue factor transcripts</rna> ( approximately 18-fold ) and an increased rate of transcription ( approximately 15-fold ) , based on nuclear run-on analysis .


Gel-shift analysis of nuclear extracts from hypoxic MPs and HeLa cells demonstrated increased DNA-binding activity at the serum response region ( SRR ; -111/+14 bp ) of the tissue factor promoter at Egr-1 motifs .

Gel-shift analysis of nuclear extracts from <protein>hypoxic MPs</protein> and <cell_line>HeLa cells</cell_line> demonstrated increased DNA-binding activity at the <dna>serum response region</dna> ( SRR ; -111/+14 bp ) of the <dna>tissue factor promoter</dna> at <dna>Egr-1 motifs</dna> .


Using 32P-labeled Egr consensus oligonucleotide , we observed induction of DNA-binding activity in nuclear extracts from hypoxic lung and HeLa cells because of activation of Egr-1 , by means of supershift analysis .

Using 32P-labeled Egr consensus oligonucleotide , we observed induction of DNA-binding activity in nuclear extracts from hypoxic lung and <cell_line>HeLa cells</cell_line> because of activation of <protein>Egr-1</protein> , by means of supershift analysis .


Transient transfection of HeLa cells with chimeric plasmids containing wild-type or mutant SRR from the tissue factor promoter showed that intact Sp1 sites are necessary for basal promoter activity , whereas the integrity of Egr-1 sites was required for hypoxia-enhanced expression .

Transient transfection of <cell_line>HeLa cells</cell_line> with <dna>chimeric plasmids</dna> containing <protein>wild-type or mutant SRR</protein> from the <dna>tissue factor promoter</dna> showed that <dna>intact Sp1 sites</dna> are necessary for basal promoter activity , whereas the integrity of <dna>Egr-1 sites</dna> was required for hypoxia-enhanced expression .


A central role for Egr-1 in hypoxia-mediated tissue factor expression was confirmed by experiments with homozygous Egr-1 null mice ; wild-type mice subjected to oxygen deprivation expressed tissue factor and showed fibrin deposition , but hypoxic homozygous Egr-1 null mice displayed neither tissue factor nor fibrin .

A central role for <protein>Egr-1</protein> in hypoxia-mediated tissue factor expression was confirmed by experiments with homozygous <protein>Egr-1</protein> null mice ; wild-type mice subjected to <protein>oxygen deprivation expressed tissue factor</protein> and showed <protein>fibrin</protein> deposition , but hypoxic homozygous <protein>Egr-1</protein> null mice displayed neither <protein>tissue factor</protein> nor <protein>fibrin</protein> .


These data delineate a novel biology for hypoxia-induced fibrin deposition , in which oxygen deprivation-induced activation of Egr-1 , resulting in expression of tissue factor , has an unexpected and central role .

These data delineate a novel biology for hypoxia-induced <protein>fibrin</protein> deposition , in which oxygen deprivation-induced activation of <protein>Egr-1</protein> , resulting in expression of <protein>tissue factor</protein> , has an unexpected and central role .


Kinetics of cytokine and NFAT gene expression in human interleukin-2-dependent T lymphoblasts stimulated via T-cell receptor .

Kinetics of cytokine and NFAT gene expression in <cell_line>human interleukin-2-dependent T lymphoblasts</cell_line> stimulated via <protein>T-cell receptor</protein> .


T cells respond to mitogenic or antigenic stimulation by proliferation and by turning on cytokine gene expression .

<cell_type>T cells</cell_type> respond to mitogenic or antigenic stimulation by proliferation and by turning on cytokine gene expression .


Here we have analysed the kinetics and nature of cytokine production in human peripheral blood-derived T lymphoblasts stimulated with anti-CD3 antibodies or Lens culinaris lectin ( LCL ) .

Here we have analysed the kinetics and nature of cytokine production in <cell_type>human peripheral blood-derived T lymphoblasts</cell_type> stimulated with <protein>anti-CD3 antibodies</protein> or <protein>Lens culinaris lectin</protein> ( <protein>LCL</protein> ) .


T cells were purified from peripheral blood mononuclear cells ( PBMC ) and primarily activated with anti-CD3 antibodies and cultured in the presence of interleukin-2 ( IL-2 ) .

<cell_type>T cells</cell_type> were purified from <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) and primarily activated with <protein>anti-CD3 antibodies</protein> and cultured in the presence of <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) .


Anti-CD3-restimulated T cells ( mainly CD8+ ) produced IL-2 , interferon-gamma ( IFN-gamma ) and tumour necrosis factor-alpha ( TNF-alpha ) and low levels of IL-4 and IL-10 transcripts and proteins .

Anti-CD3-restimulated <cell_type>T cells</cell_type> ( mainly CD8+ ) produced <protein>IL-2</protein> , <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) and <protein>tumour necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) and low levels of <rna>IL-4 and IL-10 transcripts</rna> and proteins .


No IL-6 gene expression was observed .

No <dna>IL-6 gene</dna> expression was observed .


In LCL-stimulated cells the cytokine production pattern was very similar .

In <cell_type>LCL-stimulated cells</cell_type> the cytokine production pattern was very similar .


Steady-state mRNA levels of IL-2 , IL-10 and IFN-gamma peaked at 3 hr after anti-CD3 stimulation and declined rapidly thereafter .

Steady-state mRNA levels of <protein>IL-2</protein> , <protein>IL-10</protein> and <protein>IFN-gamma</protein> peaked at 3 hr after anti-CD3 stimulation and declined rapidly thereafter .


The kinetics of TNF-alpha mRNA expression was faster , being at its peak level 1 hr after stimulation .

The kinetics of <rna>TNF-alpha mRNA</rna> expression was faster , being at its peak level 1 hr after stimulation .


Anti-CD3-stimulated IL-2 gene expression was down-regulated by protein synthesis inhibitor , whereas IL-10 , IFN-gamma and TNF-alpha genes were readily induced independent of ongoing protein synthesis .

Anti-CD3-stimulated <dna>IL-2 gene</dna> expression was down-regulated by protein synthesis inhibitor , whereas <dna>IL-10 , IFN-gamma and TNF-alpha genes</dna> were readily induced independent of ongoing protein synthesis .


T-cell receptor stimulation also induced a very rapid expression of c-jun , c-fos and NFATc1 ( NFATc ) genes , the gene products of which are involved in cytokine gene expression .

<protein>T-cell receptor</protein> stimulation also induced a very rapid expression of <dna>c-jun , c-fos and NFATc1 ( NFATc ) genes</dna> , the gene products of which are involved in cytokine gene expression .


In conclusion , the cytokines synthesized by IL-2-dependent T cells were predominantly IL-2 , IFN-gamma and TNF-alpha .

In conclusion , the <protein>cytokines</protein> synthesized by <cell_type>IL-2-dependent T cells</cell_type> were predominantly <protein>IL-2</protein> , <protein>IFN-gamma</protein> and <protein>TNF-alpha</protein> .


An animal model to study local oxidation of LDL and its biological effects in the arterial wall .


Oxidized LDL ( oxLDL ) is present in atherosclerotic lesions and is believed to play a key role in atherogenesis .


Mainly on the basis of cell culture studies , oxLDL has been shown to produce many biological effects that influence the atherosclerotic process .


To study LDL oxidation in vivo , we have established a model in which Sprague-Dawley rats are given a single injection of unmodified human LDL ( > or = 4 mg/kg body weight ) .


Within 6 hours , an accumulation of apolipoprotein B and epitopes present on oxLDL are detected in the arterial endothelium and media .

Within 6 hours , an accumulation of apolipoprotein B and <protein>epitopes</protein> present on oxLDL are detected in the arterial endothelium and media .


The presence of oxLDL is associated with activation of the transcription factor nuclear factor-kappaB in the endothelium as well as endothelial expression of intercellular adhesion molecule-1 .

The presence of oxLDL is associated with activation of the <protein>transcription factor</protein> <protein>nuclear factor-kappaB</protein> in the endothelium as well as endothelial expression of <protein>intercellular adhesion molecule-1</protein> .


Injection of LDL enriched with the antioxidant probucol resulted in arterial accumulation of apolipoprotein B , but the expression of oxLDL-specific epitopes was reduced at 24 hours .


Thus , this simple model has the potential to analyze the mechanisms behind and biological effects of LDL oxidation in vivo .


Molecular mechanisms of promoter regulation of the gp34 gene that is trans-activated by an oncoprotein Tax of human T cell leukemia virus type I .

Molecular mechanisms of promoter regulation of the <dna>gp34 gene</dna> that is trans-activated by an <protein>oncoprotein Tax</protein> of human T cell leukemia virus type I .


We investigated the molecular mechanism of transcriptional activation of the gp34 gene by the Tax oncoprotein of human T cell leukemia virus type I ( HTLV-I ) .

We investigated the molecular mechanism of transcriptional activation of the <dna>gp34 gene</dna> by the <protein>Tax oncoprotein</protein> of human T cell leukemia virus type I ( HTLV-I ) .


gp34 is a type II transmembrane molecule belonging to the tumor necrosis factor family and is constitutively expressed on HTLV-I-producing cells but not normal resting T cells .

<protein>gp34</protein> is a <protein>type II transmembrane molecule</protein> belonging to the tumor necrosis factor family and is constitutively expressed on <cell_type>HTLV-I-producing cells</cell_type> but not <cell_type>normal resting T cells</cell_type> .


The transcriptional regulatory region of the gp34 gene was activated by HTLV-I Tax in the human T cell line Jurkat , in which endogenous gp34 is induced by Tax .

The transcriptional regulatory region of the <dna>gp34 gene</dna> was activated by HTLV-I <protein>Tax</protein> in the <cell_line>human T cell line Jurkat</cell_line> , in which endogenous <protein>gp34</protein> is induced by <protein>Tax</protein> .


Sequence analysis demonstrated that two NF-kappaB-like elements ( 1 and 2 ) were present in the regulatory region .

Sequence analysis demonstrated that two <dna>NF-kappaB-like elements</dna> ( 1 and 2 ) were present in the <dna>regulatory region</dna> .


Both NF-kappaB-like elements were able to bind to NF-kappaB or its related factor ( s ) in a Tax -dependent manner .

Both <dna>NF-kappaB-like elements</dna> were able to bind to <protein>NF-kappaB</protein> or its related factor ( s ) in a <protein>Tax</protein> -dependent manner .


Chloramphenicol acetyltransferase assays indicated that NF-kappaB-like element 1 was Tax -responsive , although the activity was lower than that the native promoter .

<protein>Chloramphenicol acetyltransferase</protein> assays indicated that <dna>NF-kappaB-like element 1</dna> was <protein>Tax</protein> -responsive , although the activity was lower than that the <dna>native promoter</dna> .


NF-kappaB -like element 2 elevated promoter activity when combined with NF-kappaB-like element 1 , indicating cooperative function of the elements for maximum promoter function .

<protein>NF-kappaB</protein> -like element 2 elevated promoter activity when combined with <dna>NF-kappaB-like element 1</dna> , indicating cooperative function of the elements for maximum promoter function .


Unlike typical NF-kappaB elements , the NF-kappaB-like elements in gp34 were not activated by treatment of Jurkat cells with phorbol ester despite induction of the NF-kappaB -like binding activity .

Unlike typical <dna>NF-kappaB elements</dna> , the <dna>NF-kappaB-like elements</dna> in <protein>gp34</protein> were not activated by treatment of <cell_line>Jurkat cells</cell_line> with phorbol ester despite induction of the <protein>NF-kappaB</protein> -like binding activity .


Chloramphenicol acetyltransferase reporter assays using the region upstream of the NF-kappaB-like elements identified an upstream region that reduced transcription from cognate and noncognate core promoters in a Tax-independent manner .

<protein>Chloramphenicol acetyltransferase</protein> reporter assays using the region upstream of the <dna>NF-kappaB-like elements</dna> identified an upstream region that reduced transcription from <dna>cognate and noncognate core promoters</dna> in a Tax-independent manner .


Our results imply complex regulation of expression of the gp34 gene and suggest implication of gp34 in proliferation of HTLV-I infected T cells .

Our results imply complex regulation of expression of the <dna>gp34 gene</dna> and suggest implication of <protein>gp34</protein> in proliferation of HTLV-I infected T cells .


beta-Amyloid fibrils activate parallel mitogen-activated protein kinase pathways in microglia and THP1 monocytes .

<protein>beta-Amyloid fibrils</protein> activate parallel <protein>mitogen-activated protein kinase</protein> pathways in <cell_type>microglia</cell_type> and <cell_line>THP1 monocytes</cell_line> .


The senile plaques of Alzheimer 's disease are foci of local inflammatory responses , as evidenced by the presence of acute phase proteins and oxidative damage .

The senile plaques of Alzheimer 's disease are foci of local inflammatory responses , as evidenced by the presence of <protein>acute phase proteins</protein> and oxidative damage .


Fibrillar forms of beta-amyloid ( Abeta ) , which are the primary constituents of senile plaques , have been shown to activate tyrosine kinase-dependent signal transduction cascades , resulting in inflammatory responses in microglia .

<protein>Fibrillar forms</protein> of <protein>beta-amyloid</protein> ( <protein>Abeta</protein> ) , which are the primary constituents of senile plaques , have been shown to activate tyrosine kinase-dependent signal transduction cascades , resulting in inflammatory responses in <cell_type>microglia</cell_type> .


However , the downstream signaling pathways mediating Abeta -induced inflammatory events are not well characterized .

However , the downstream signaling pathways mediating <protein>Abeta</protein> -induced inflammatory events are not well characterized .


We report that exposure of primary rat microglia and human THP1 monocytes to fibrillar Abeta results in the tyrosine kinase -dependent activation of two parallel signal transduction cascades involving members of the mitogen-activated protein kinase ( MAPK ) superfamily .

We report that exposure of <cell_type>primary rat microglia</cell_type> and <cell_line>human THP1 monocytes</cell_line> to <protein>fibrillar Abeta</protein> results in the <protein>tyrosine kinase</protein> -dependent activation of two parallel signal transduction cascades involving members of the <protein>mitogen-activated protein kinase ( MAPK ) superfamily</protein> .


Abeta stimulated the rapid , transient activation of extracellular signal-regulated kinase 1 ( ERK1 ) and ERK2 in microglia and ERK2 in THP1 monocytes .

<protein>Abeta</protein> stimulated the rapid , transient activation of <protein>extracellular signal-regulated kinase 1</protein> ( <protein>ERK1</protein> ) and <protein>ERK2</protein> in <cell_type>microglia</cell_type> and <protein>ERK2</protein> in <cell_line>THP1 monocytes</cell_line> .


A second superfamily member , p38 MAPK , was also activated with similar kinetics .

A second <protein>superfamily member</protein> , <protein>p38 MAPK</protein> , was also activated with similar kinetics .


Scavenger receptor and receptor for advanced glycated end products ( RAGE ) ligands failed to activate ERK and p38 MAPK in the absence of significant increases in protein tyrosine phosphorylation , demonstrating that scavenger receptors and RAGE are not linked to these pathways .

<protein>Scavenger receptor</protein> and <protein>receptor for advanced glycated end products</protein> ( <protein>RAGE</protein> ) ligands failed to activate <protein>ERK</protein> and <protein>p38 MAPK</protein> in the absence of significant increases in protein tyrosine phosphorylation , demonstrating that <protein>scavenger receptors</protein> and <protein>RAGE</protein> are not linked to these pathways .


Importantly , the stress-activated protein kinases ( SAPKs ) were not significantly activated in response to Abeta .

Importantly , the <protein>stress-activated protein kinases</protein> ( <protein>SAPKs</protein> ) were not significantly activated in response to <protein>Abeta</protein> .


Downstream effectors of the MAPK signal transduction cascades include MAPKAP kinases , such as RSK1 and RSK2 , as well as transcription factors .

Downstream effectors of the MAPK signal transduction cascades include <protein>MAPKAP kinases</protein> , such as <protein>RSK1</protein> and <protein>RSK2</protein> , as well as <protein>transcription factors</protein> .


Exposure of microglia and THP1 monocytes to Abeta resulted in the activation of RSK1 and RSK2 and phosphorylation of cAMP response element-binding protein at Ser133 , providing a mechanism for Abeta -induced changes in gene expression

Exposure of <cell_type>microglia</cell_type> and <cell_line>THP1 monocytes</cell_line> to <protein>Abeta</protein> resulted in the activation of <protein>RSK1</protein> and <protein>RSK2</protein> and phosphorylation of <protein>cAMP response element-binding protein</protein> at Ser133 , providing a mechanism for <protein>Abeta</protein> -induced changes in gene expression


Regulation of cellular retinoic acid binding protein ( CRABP II ) during human monocyte differentiation in vitro .

Regulation of <protein>cellular retinoic acid binding protein</protein> ( <protein>CRABP II</protein> ) during <cell_type>human monocyte</cell_type> differentiation in vitro .


Cellular retinoic acid binding proteins ( CRABP ) are low molecular weight proteins whose precise function remains unknown .

<protein>Cellular retinoic acid binding proteins</protein> ( <protein>CRABP</protein> ) are <protein>low molecular weight proteins</protein> whose precise function remains unknown .


They bind retinoids and may thereby modulate the intracellular steady-state concentration of retinoids .


Whereas CRABP I is ubiquitously expressed , CRABP II is mainly detected in various cell types of the skin .

Whereas <protein>CRABP I</protein> is ubiquitously expressed , <protein>CRABP II</protein> is mainly detected in various cell types of the skin .


By representative difference analysis we found that CRABP II is also strongly expressed in human monocyte-derived macrophages ( MAC ) but not in freshly isolated monocytes ( MO ) .

By representative difference analysis we found that <protein>CRABP II</protein> is also strongly expressed in <cell_type>human monocyte-derived macrophages</cell_type> ( <cell_type>MAC</cell_type> ) but not in <cell_type>freshly isolated monocytes</cell_type> ( <cell_type>MO</cell_type> ) .


The CRABP II mRNA was gradually upregulated during differentiation from MO to MAC in the presence of 2 % serum .

The <rna>CRABP II mRNA</rna> was gradually upregulated during differentiation from <cell_type>MO</cell_type> to <cell_type>MAC</cell_type> in the presence of 2 % serum .


Adherence , which is important for MO differentiation , induced CRABP II expression , but the addition of 10 ( -7 ) M retinoic acid inhibited the upregulation of CRABP II expression during MO/MAC differentiation .

Adherence , which is important for <cell_type>MO</cell_type> differentiation , induced <protein>CRABP II</protein> expression , but the addition of 10 ( -7 ) M retinoic acid inhibited the upregulation of <protein>CRABP II</protein> expression during MO/MAC differentiation .


As MO can differentiate along the classical pathway not only to MAC but also to dendritic cells we analyzed the expression of CRABP II in MO-derived dendritic cells cultured with 10 % FCS , IL-4 , and GM-CSF .

As <cell_type>MO</cell_type> can differentiate along the classical pathway not only to <cell_type>MAC</cell_type> but also to dendritic cells we analyzed the expression of <protein>CRABP II</protein> in <cell_type>MO-derived dendritic cells</cell_type> cultured with 10 % <protein>FCS</protein> , <protein>IL-4</protein> , and <protein>GM-CSF</protein> .


In contrast to MAC , MO-derived dendritic cells showed an extremely low expression of CRABP II .

In contrast to <cell_type>MAC</cell_type> , <cell_type>MO-derived dendritic cells</cell_type> showed an extremely low expression of <protein>CRABP II</protein> .


From these results we conclude ( 1 ) that the availability and the metabolism of retinoids may be different in MAC compared to MO and dendritic cells and ( 2 ) that this may influence differentiation and activation of those cells .

From these results we conclude ( 1 ) that the availability and the metabolism of retinoids may be different in <cell_type>MAC</cell_type> compared to <cell_type>MO</cell_type> and <cell_type>dendritic cells</cell_type> and ( 2 ) that this may influence differentiation and activation of those cells .


Transcription factor B-cell-specific activator protein ( BSAP ) is differentially expressed in B cells and in subsets of B-cell lymphomas .

<protein>Transcription factor B-cell-specific activator protein</protein> ( <protein>BSAP</protein> ) is differentially expressed in <cell_type>B cells</cell_type> and in subsets of B-cell lymphomas .


The paired box containing gene PAX-5 encodes the transcription factor BSAP ( B-cell-specific activator protein ) , which plays a key role in B-lymphocyte development .

The <dna>paired box containing gene</dna> <dna>PAX-5</dna> encodes the <protein>transcription factor</protein> <protein>BSAP</protein> ( <protein>B-cell-specific activator protein</protein> ) , which plays a key role in B-lymphocyte development .


Despite its known involvement in a rare subtype of non-Hodgkin 's lymphoma ( NHL ) , a detailed examination of BSAP expression in NHL has not been previously reported .

Despite its known involvement in a rare subtype of non-Hodgkin 's lymphoma ( NHL ) , a detailed examination of <protein>BSAP</protein> expression in NHL has not been previously reported .


In this study , we analyzed normal and malignant lymphoid tissues and cell lines , including 102 cases of B-cell NHL , 23 cases of T- and null-cell NHL , and 18 cases of Hodgkin 's disease .

In this study , we analyzed normal and malignant lymphoid tissues and <cell_line>cell lines</cell_line> , including 102 cases of B-cell NHL , 23 cases of T- and null-cell NHL , and 18 cases of Hodgkin 's disease .


Normal lymphoid tissues showed strong nuclear BSAP expression in mantle zone B cells , less intense reactivity in follicular center B cells , and no expression in cells of the T-cell-rich zones .

Normal lymphoid tissues showed strong nuclear <protein>BSAP</protein> expression in <cell_type>mantle zone B cells</cell_type> , less intense reactivity in <cell_type>follicular center B cells</cell_type> , and no expression in cells of the T-cell-rich zones .


Monocytoid B cells showed weak expression , whereas plasma cells and extrafollicular large transformed B cells were negative .

<cell_type>Monocytoid B cells</cell_type> showed weak expression , whereas <cell_type>plasma cells</cell_type> and <cell_type>extrafollicular large transformed B cells</cell_type> were negative .


Of the 102 B-cell NHLs , 83 ( 81 % ) demonstrated BSAP expression .

Of the 102 B-cell NHLs , 83 ( 81 % ) demonstrated <protein>BSAP</protein> expression .


All of the 13 ( 100 % ) B-cell chronic lymphocytic leukemias ( B-CLLs ) , 21 of ( 100 % ) mantle cells ( MCLs ) , and 20 of 21 ( 95 % ) follicular lymphomas ( FLs ) were positive .

All of the 13 ( 100 % ) B-cell chronic lymphocytic leukemias ( B-CLLs ) , 21 of ( 100 % ) <cell_type>mantle cells</cell_type> ( <cell_type>MCLs</cell_type> ) , and 20 of 21 ( 95 % ) follicular lymphomas ( FLs ) were positive .


Moderate staining intensities were found in most B-CLL and FL cases , whereas most MCLs showed strong reactions , paralleling the strong reactivity of nonmalignant mantle cells .

Moderate staining intensities were found in most B-CLL and FL cases , whereas most <cell_type>MCLs</cell_type> showed strong reactions , paralleling the strong reactivity of <cell_type>nonmalignant mantle cells</cell_type> .


Eight of 12 ( 67 % ) marginal zone lymphoma cases showed negative or low BSAP levels , and 17 of 24 ( 71 % ) large B-cell lymphomas displayed moderate to strong expression .

Eight of 12 ( 67 % ) marginal zone lymphoma cases showed negative or low <protein>BSAP</protein> levels , and 17 of 24 ( 71 % ) large B-cell lymphomas displayed moderate to strong expression .


of the 23 T- and null-cell lymphomas reacted with the BSAP antisera , whereas in Hodgkin 's disease , 2 of 4 ( 50 % ) nodular lymphocytic predominance and 5 of 14 ( 36 % ) classical cases showed weak nuclear or nucleolar BSAP reactions in a fraction of the tumor cells .

of the 23 T- and null-cell lymphomas reacted with the <protein>BSAP</protein> antisera , whereas in Hodgkin 's disease , 2 of 4 ( 50 % ) nodular lymphocytic predominance and 5 of 14 ( 36 % ) classical cases showed weak nuclear or nucleolar <protein>BSAP</protein> reactions in a fraction of the <cell_type>tumor cells</cell_type> .


Western blot analysis showed a 52-kD BSAP band in B-cell lines , but not in non-B-cell or plasma cell lines .

Western blot analysis showed a 52-kD <protein>BSAP</protein> band in <cell_line>B-cell lines</cell_line> , but not in <cell_line>non-B-cell or plasma cell lines</cell_line> .


We conclude that BSAP expression is largely restricted to lymphomas of B-cell lineage and that BSAP expression varies in B-cell subsets and subtypes of B-cell NHL .

We conclude that <protein>BSAP</protein> expression is largely restricted to lymphomas of <cell_type>B-cell lineage</cell_type> and that <protein>BSAP</protein> expression varies in <cell_type>B-cell subsets</cell_type> and subtypes of B-cell NHL .


The high levels of BSAP , especially those found in large-cell lymphomas and in some follicular lymphomas , may be a consequence of deregulated gene expression and suggest a possible involvement of PAX-5 in certain B-cell malignancies .

The high levels of <protein>BSAP</protein> , especially those found in <cell_type>large-cell lymphomas</cell_type> and in some <cell_type>follicular lymphomas</cell_type> , may be a consequence of deregulated gene expression and suggest a possible involvement of <dna>PAX-5</dna> in certain B-cell malignancies .


This is a US government work .


There are no restrictions on its use .


Mitogen and growth factor-induced activation of a STAT-like molecule in channel catfish lymphoid cells .

Mitogen and growth factor-induced activation of a <protein>STAT-like molecule</protein> in <cell_type>channel catfish lymphoid cells</cell_type> .


This article describes the identification of a putative STAT molecule in the channel catfish ( Ictalurus punctatus ) , the first report of such a molecule in a 'lower ' vertebrate .

This article describes the identification of a <protein>putative STAT molecule</protein> in the channel catfish ( Ictalurus punctatus ) , the first report of such a molecule in a 'lower ' vertebrate .


A monoclonal antibody against human STAT6 recognizes an approximately 100 kDa molecule that becomes activated and translocates to the nucleus upon both growth factor and mitogen stimulation of catfish leukocytes .

A <protein>monoclonal antibody</protein> against <protein>human STAT6</protein> recognizes an approximately <protein>100 kDa molecule</protein> that becomes activated and translocates to the nucleus upon both growth factor and mitogen stimulation of catfish leukocytes .


This presumed catfish STAT binds the mammalian interferon-gamma activation site , a known motif of mammalian STAT binding , as shown by electromobility shift assays .

This presumed <protein>catfish STAT</protein> binds the <dna>mammalian interferon-gamma activation site</dna> , a known motif of mammalian STAT binding , as shown by electromobility shift assays .


Purification of the proteins present in these DNA complexes confirms that the catfish reactive molecule binds to the interferon-gamma activation site sequence .

Purification of the proteins present in these <protein>DNA complexes</protein> confirms that the catfish reactive molecule binds to the <dna>interferon-gamma activation site sequence</dna> .


These results suggest that STAT molecules have been highly conserved in vertebrate evolution .

These results suggest that <protein>STAT molecules</protein> have been highly conserved in vertebrate evolution .


Isolation and analysis of a T cell clone variant exhibiting constitutively phosphorylated Ser133 cAMP response element-binding protein .

Isolation and analysis of a <cell_line>T cell clone variant</cell_line> exhibiting constitutively <protein>phosphorylated Ser133 cAMP response element-binding protein</protein> .