Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A monoclonal antibody (mAb), designated SCH94.03, which promotes central nervous system remyelination in susceptible mice infected with Theiler's virus, has been proposed to be a natural autoantibody based on its germline immunoglobulin sequence. To identify the potential antigens recognized by mAb SCH94.03, a rat brain lambda gtll cDNA expression library was screened with this antibody. Nine independent clones were identified. Five clones were identical or highly similar to known cDNAs or proteins (rat kinesin light chain, mouse thrombospondin 1, mouse oncofetal antigen, RNA polymerase beta subunit and nuclear phosphoprotein). Four clones, designated REM#1, REM#2, REM#3 and REM#4, contained open reading frames, but were not homologous to any known genes or proteins. The reactivity of SCH94.03 with all nine clones was specific in that all nine clones identified contained continuous open reading frames and none of nine control IgM mAbs showed reactivity with any of the nine cDNA clones. The precise specificity of binding of mAb SCH94.03 was demonstrated by the absence of reactivity to the identified clones with IgM Ab from B cell lymphoma (CH12) which has identical cDNA sequences with mAb SCH94.03, but differ only in the heavy chain CDR3 N region. Our studies support the hypothesis that highly polyreactive natural autoantibodies can play a role in promoting central nervous system remyelination.
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PMID:A monoclonal autoantibody which promotes central nervous system remyelination is highly polyreactive to multiple known and novel antigens. 864 59

Primary effusion lymphoma (PEL) is a distinct clinicopathologic entity associated with Kaposi's sarcoma-associated herpes virus (KSHV). Several cytokines, including interleukin-6 (IL-6), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) may be important for survival of KS cells. However, little is known about the interaction of cytokines with KSHV-infected lymphocytes from PEL. Therefore, we investigated what cytokines were produced by KSHV-infected PEL cell lines (KS-1, BC-1, BC-2), what cytokine receptors were expressed by these cells, what response these cells had to selected cytokines, and what was the effect of IL-6 antisense phosphorothioated oligonucleotides. Reverse transcriptase-polymerase chain reaction (RT-PCR) and protein studies showed that these three cell lines produced IL-10, IL-6, and the receptors for IL-6. The granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1beta, IL-8, IL-12, bFGF, PDGF, and c-kit transcripts were not detected in the cell lines. High levels (0.7 to 5 ng/mL/10(6) cells/48 hours) of IL-6 protein were consistently detected in supernatants of the cell lines by enzyme-linked immunosorbent assay (ELISA) tests. In clonogenic assays, interferon-alpha (IFN-alpha) and IFN-gamma suppressed the clonal growth of the PEL cells, but GM-CSF, IL-4, IL-6, IL-8, IL-10, and oncostatin M did not change it. We examined for several autocrine loops that have been suggested to occur in KS. Experiments using antisense oligonucleotides showed that the clonal growth of KS-1 and BC-1 was nearly 100% inhibited by IL-6 antisense oligonucleotides (10 micromol/L), but not at all by either oligonucleotides (</=10 micromol/L) to IL-6 sense, IL-6 scrambled, viral IL-6 (vIL-6) antisense, or IL-10 antisense. Furthermore, the IL-6 antisense oligonucleotides had no effect on two B-cell lymphoma cell lines, which were not infected with KSHV. Addition of IL-6 antibody did not inhibit clonal growth of any of the cell lines. Taken together, we have defined the cytokines and their receptors expressed on PEL cells and have found that these cells synthesized IL-6 and IL-6 receptors; interruption of this pathway by IL-6 antisense oligonucleotides specifically prevented the growth of these cells. These findings will offer potential new therapeutic strategies for PEL.
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PMID:Mechanisms of growth control of Kaposi's sarcoma-associated herpes virus-associated primary effusion lymphoma cells. 951 48

T-cell lymphoma in patients infected with HIV is much less common than B-cell lymphoma. We describe two cases of HIV-associated extranodal lymphoma that showed Toutonlike tumor giant cells and mononuclear large lymphoma cells. Both cell types expressed T-cell-associated antigens, including CD3, CD5, CD43, and CD45RO, and were CD4- and CD30-positive and negative for all B-lineage-associated antigens. Both cases showed T-cell receptor gamma chain gene rearrangements using the polymerase chain reaction and were negative for the Epstein-Barr virus by in situ hybridization. Despite the expression of CD30 by the multinucleated cells, both cases were negative for ALK1 by immunohistochemistry and failed to show evidence of the nucleophosmin-anaplastic lymphoma kinase fusion product characteristic of t(2;5) using the reverse-transcriptase polymerase chain reaction. Although rare, CD4-positive, T-cell lymphoma with Toutonlike giant cells may be a distinct type of HIV-associated malignant lymphoma.
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PMID:Peripheral T-cell lymphoma with Toutonlike tumor giant cells associated with HIV infection: report of two cases. 1032 82

The objective of this study was to examine placentas after delivery from normal, healthy patients at term gestation. The placentas were from elective cesarean sections (n = 10, prior to the onset of labor) and spontaneous vaginal delivery (n = 10, after labor). We found that deoxyribonucleic acid laddering was present in all placentas and consistent with the pattern found in tissues that undergo apoptosis. Paraffin-embedded sections of placental villi stained by the in situ terminal deoxynucleotidyl transferase mediated biotinylated dUTP nick end labeling method revealed positive apoptotic nuclei in the placental villi. Reverse-transcriptase polymerase chain reaction demonstrated expression of messenger RNA for testosterone-repressed prostate message 2 and B cell lymphoma/leukemia-2 in the placenta. Our data demonstrate that apoptosis occurs in human term placenta.
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PMID:Apoptosis in human term placenta. A morphological and gene expression study. 1096 89

The BCL10 gene was identified at the breakpoint region of the t(1;14)(p22;q32) translocation in mucosa-associated lymphoid tissue lymphoma. Initially, mutations in the BCL10 gene were reported to occur at a high frequency in various types of lymphomas and solid tumors. However, subsequent studies showed that the mutations were rarely recognized. To evaluate the frequency and spectrum of its mutations in B-cell non-Hodgkin's lymphoma (B-NHL), we screened 56 cases with B-NHL by mutation analysis of exons 2 and 3 of the gene. In addition to 2 polymorphisms, a frame-shift mutation and a missense mutation were identified in 2 cases (3.6%): 1 with diffuse large B-cell lymphoma and the other with mantle cell lymphoma. Both cases showed mutations within exon 3, resulting in a C-terminal truncation in the former and a C-terminal amino acid substitution in the latter. Reverse transcriptase-polymerase chain reaction analysis of the former case revealed that both the mutated and the wild-type alleles were transcribed with or without a sequence modification. Our results, together with recent reports, indicate that BCL10 gene mutations take place in a small population of B-NHL and are not associated with specific histological subtypes.
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PMID:Low frequency of BCL10 gene mutations in B-cell non-Hodgkin's lymphoma. 1137 35

Primary mediastinal B-cell lymphoma (PMBL) is a subentity of diffuse large B-cell lymphoma with characteristic clinical, histomorphologic, immunophenotypical, and genetic features. Unlike other B-cell lymphomas, PMBL has not yet been the subject of comprehensive molecular studies on the rearranged immunoglobulin (Ig) gene. Such investigations have proved essential to obtaining information about the differentiation stage of the lymphomagenic B cell. In the present study, the clonally rearranged immunoglobulin heavy-chain gene of 13 PMBL cases is analyzed by polymerase chain reaction (PCR) in conjunction with cloning and DNA sequencing. Twelve of 13 rearrangements were potentially functional. All clonally rearranged immunoglobulin genes bore a high load of somatic mutations (average, 13.0%), which appeared to be selected for a functional antibody in the majority of cases. The comparison of cloned PCR products revealed no evidence of ongoing mutation of the immunoglobulin variable gene. By means of reverse-transcriptase PCR, lymphoma-specific immunoglobulin transcripts were detected in 8 of 13 cases, all of which were of the postswitched type, whereas immunoglobulin protein expression was undetectable except for 1 case. A PMBL cell line, MedB-1, generated from an IgG(-) parental tumor, constitutively expressed IgG protein in a subset of cells, which was moderately suppressed by interleukin-4 and up-regulated in the presence of dexamethasone. PMBL is thus characterized by a heavily mutated, class-switched immunoglobulin gene without evidence of ongoing mutational activity. Moreover, our data indirectly suggest that regulation by extrinsic signals contributes to the immunoglobulin-negative phenotype of PMBL.
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PMID:Isotype-switched immunoglobulin genes with a high load of somatic hypermutation and lack of ongoing mutational activity are prevalent in mediastinal B-cell lymphoma. 1167 49

Plasmablastic lymphoma is a relatively new entity that is considered to be a diffuse large B-cell lymphoma with an unique immunophenotype and a predilection for the oral cavity. We present a 50 year-old HIV-positive, bisexual, white male with a CD4 count 300/mm(3) and a viral HIV-RNA polymerase chain reaction (PCR) load of 237 copies/ml, who developed a painful, purple-red mass in the edentulous area of the maxillary right first molar. Erythematous gingival enlargements of the interdental papillae were seen in three of the dental quadrants. In addition, the patient was being managed with antiretroviral therapy and liposomal doxorubicin for recurrent cutaneous Kaposi's sarcoma (KS). Although oral KS was suspected, the gingival lesions were biopsied because they were refractory to chemotherapy and a lymphoma could not be excluded. Histopathologic examination revealed a lymphoid malignant neoplasm, consistent with a plasmablastic lymphoma. Immunoreactivity with vs38c, CD79a, kappa light chain, and IgG was readily identified in tumor cells; while only focal cells expressed CD20 and LCA (CD45RB). CD56, CD3, lambda light chain, and EMA were non-reactive. EBV was detected in the tumor by Southern hybridization, PCR amplification, in situ hybridization for EBER-1 DNA, and immunohistochemistry for latent membrane protein-1. The same tumor was negative for HHV-8 by PCR. Recognition of plasmablastic lymphoma is important, because it represents an HIV-associated malignancy that predominantly involves the oral cavity, may mimic KS and has a poor prognosis.
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PMID:Plasmablastic lymphoma: an HIV-associated entity with primary oral manifestations. 1175 27

BCL6 translocation affecting the chromosomal band 3q27 can involve a number of non-immunoglobulin (non-IG) gene loci as partners. We report here that the gene for interleukin-21 receptor (IL-21R) is the partner of BCL6 in t(3;16)(q27;p11) translocation. The two breakpoints on 16p11 of a lymphoma cell line YM and case no. 1012 with diffuse large B-cell lymphoma, both of which carried t(3;16), were localized within the 27-kb intron 1 of IL-21R. As a result of t(3;16), the promoter region of IL-21R was substituted for the regulatory sequences of BCL6 in the same transcriptional orientation. Reverse transcriptase-mediated polymerase chain reaction revealed chimeric mRNA consisting of two non-coding exons 1a/1b of IL-21R and coding exons of BCL6 in both lymphoma cells. Fluorescence in situ chromosomal hybridization of YM metaphase cells revealed fusion signals that contained both the BCL6 and IL-21R sequences on the der(3)t(3;16) chromosome. IL-21R was actively transcribed in YM cells, while BCL6 that was under the control of the IL-21R promoter was only moderately expressed at the mRNA and protein level. We constructed expression plasmid of BCL6 that followed the promoter sequences of IL-21R. COS-7 cells transiently transfected with the plasmid expressed high level Bcl-6 protein and displayed nuclear staining with a characteristic punctate pattern by immunofluorescence, indicating that expression of BCL6 can be enhanced by t(3;16). This study added to the list of non-IG partners of BCL6 translocations a new class of gene, i.e. cytokine receptor gene, the expression of which is closely associated with lymphoid cells.
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PMID:The gene for interleukin-21 receptor is the partner of BCL6 in t(3;16)(q27;p11), which is recurrently observed in diffuse large B-cell lymphoma. 1182 49

The bcl-x gene product has two forms, bcl-xl and bcl-xs. The bcl-xl form, similar to bcl-2, inhibits apoptosis. Reverse transcriptase-polymerase chain reaction/single-stranded conformation polymorphism (RT-PCR-SSCP) gel analysis was used to screen for mutations of the bcl-xl transcript of 50 non-Hodgkin's lymphoma (NHL) cases. One missense mutation in a patient with diffuse large B-cell lymphoma was found. Sequence analysis of this case showed that AGC (Ser) was mutated to GGC (Gly) in codon 154. An examination of mutation and/or polymorphism in born marrow samples of this case and 50 normal controls by the RT-PCR-SSCP method could not detect bandshifts. Mutation of the bcl-x gene in NHL has not been reported previously. There is a possibility that mutation of the bcl-x gene play a role in the tumorigenesis of NHL.
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PMID:Mutation of bcl-x gene in non-Hodgkin's lymphoma. 1183 37

Primary effusion lymphoma is a form of diffuse large B-cell lymphoma with neoplastic cells largely limited to proliferation within major body cavities. Human herpes virus-8 is both integral to and required for an unequivocal diagnosis of primary effusion lymphoma. Prior methods for virus identification include DNA extraction with Southern blot analysis or in situ hybridization from paraffin-embedded samples. Our aim is to examine the utility of human herpesvirus-8 identification performed directly on smears from effusion samples by reverse transcriptase in situ polymerase chain reaction in patients with primary effusion lymphoma. Smears and cell block of body cavity fluids from five patients with effusions (three pleural, one peritoneal, and one both pleural and peritoneal) were examined microscopically by conventional Papanicolaou and Romanowsky (Diff-Quik) staining, and by reverse transcriptase in situ polymerase chain reaction for human herpesvirus-8 detection. In situ hybridization was performed also for Epstein-Barr virus (EBER-1, -2), T-cell receptor-beta, and kappa (kappa) and lambda (lambda) mRNA in all cases. Five adults ranged from 40-81 years of age. Three adults were HIV positive, one was a renal transplant recipient, and the oldest patient (Case 3) had the unusual distinction of a normal immune status. Two of three HIV-seropositive patients had concurrent Kaposi sarcoma. All samples were cytologically similar with lymphocytes having large-cell, plasmablastic, and immunoblastic morphology. Malignant cells from effusions were as follows: human herpesvirus-8 positive (all five cases), exhibited kappa monoclonal light chain (five cases), Epstein-Barr virus positive (three cases), and T-cell beta-gene receptor positive (two cases). Diffuse large B-cell lymphoma was evident in one peritoneal nodule (< 10% human herpesvirus-8 positive cells in contrast to > 90% positive in effusions, all kappa positive). Six other tissue specimens (lung, bone marrow, spleen, lymph node) were human herpesvirus-8 negative, and showed no evidence of lymphoma. Reverse transcriptase in situ polymerase chain reaction demonstrated near-complete restriction of human herpesvirus-8-infected malignant lymphoid cells to those in body cavities. Definitive diagnosis of primary effusion lymphoma is possible directly from cytologic smears/cell block by combining cytologic morphology with reverse transcriptase in situ polymerase chain reaction detection of human herpesvirus-8.
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PMID:Primary effusion lymphoma: cytopathologic diagnosis using in situ molecular genetic analysis for human herpesvirus 8. 1221 12


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