Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytoplasmic DNA from mouse myeloma cells comprised between 1% and 2% of the total cellular DNA. Detergent-prepared cytoplasmic lysate consisted mainly of 8-S and 22-S species. While these DNA species were present in the 13000 times g pellet of the detergent-prepared cytoplasmic lysate, only the light DNA species was present in the 13000 times g supernatant fraction. In neutral CsCl gradients the DNA of both cytoplasmic fractions had a buoyant density of 1700 g/cm3, which is identical to that of nuclear DNA. The similarity between the cytoplasmic and nuclear DNA was also demonstrated by analysis on alkaline CsCl gradients. A small proportion of closed-circular DNA, presumably of mitochondrial origin, was demonstrated only in cytoplasmic fraction obtained from mechanically disrupted cells and not in detergent-prepared cytoplasmic lysate. It was found that poly (A)-containing mRNA and 28-S ribosomal RNA hybridized to about the same extent to the cytoplasmic DNA as compared to nuclear DNA. The results indicate that most of the cytoplasmic DNA in myeloma cells is similar to nuclear DNA and does not consist of mitochondrial DNA.
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PMID:Characterization of cytoplasmic DNA of mouse-myeloma cells. 120 39

DNA-dependent RNA polymerase A (or 1) was purified from murine myeloma MOPC 21 by diethylaminoethyl Sephadex chromatography. Further separation from DNA polymerases, protein kinase and DNA endonuclease was accomplished by polyriboadenylate-Sepharose affinity chromatography followed by gradient centrifugation. Yields following chromatography were 100%, but following gradient centrifugation only 25 to 30% of the activity remained. Addition of low-molecular-weight components increased yields to 50 to 60%. Several species of myeloma polymerase A could be detected, and subunits of 190,000 and 125,000 daltons were identified. No evidence of phosphorylation of the polymerase was found.
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PMID:Purification, analysis, and subunits of myeloma (MOPC 21) DNA-dependent RNA polymerase A (1) by polyriboadenylate-sepharose. 125 70

Interferons produced by recombinant DNA technology began phase I trials little more than a decade ago. Today interferon alfa-2 is a mainstay in the treatment of hairy cell leukemia, and has demonstrated benefit in the more common chronic myelogenous leukemia. Interferon alfa-2 also has activity in other hematologic malignancies, including indolent non-Hodgkin's lymphomas, cutaneous T-cell lymphomas, T-cell lymphoma, and multiple myeloma, and in solid tumors such as disseminated melanoma, renal cell carcinoma, Kaposi's sarcoma, endocrine pancreatic tumors, and malignant carcinoid tumors. Interferon alfa, beta, and gamma remain under investigation to define potential roles in ovarian, breast, bladder, and cervical carcinomas and gliomas. The greatest value of the interferons will be in prolonging the disease-free interval when used in combination with other treatment modalities, including surgery, radiation, chemotherapy, and other biologic agents.
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PMID:Current status of interferons in the treatment of cancer. 128 Jan 53

Anti-DNA antibodies in systemic lupus erythematosus (SLE) sera were analyzed using an antiidiotype designated 8.12 which recognizes a determinant on lambda light chains highly expressed in SLE sera. Eight of ten normal individuals had peripheral blood lymphocytes which produced high-titered 8.12-positive antibodies, following transformation with Epstein Barr virus, implying that the 8.12-reactive sequence originates in the germline gene (GLG). Of 58 SLE sera, 32 contained elevated titers of 8.12-reactive antibodies. Twenty-three of these sera had 8.12-reactive anti-DNA antibodies, suggesting a strong correlation between 8.12 idiotype and DNA binding. Moreover, 20 of 26 8.12-reactive IgG antibodies and only 4 of 10 8.12-reactive IgM antibodies bound DNA (P less than 0.05). These observations strengthen our previous findings in myeloma sera that DNA binding is associated with IgG isotype in the 8.12 idiotype system and suggest that the acquisition of anti-DNA reactivity in antibodies bearing the GLG idiotype 8.12 is achieved by somatic mutation, a feature of an antigen-driven response.
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PMID:Lupus anti-DNA antibodies bearing the 8.12 idiotype appear to be somatically mutated. 131 42

IgE is produced by B lymphocytes that have undergone a deletional rearrangement of their Ig H chain gene locus, a rearrangement that joins the switch region of the mu gene, S mu, with the corresponding region of the epsilon gene, S epsilon. To examine the resulting composite S mu-S epsilon junctions of human lymphoid cells, we have used a polymerase chain reaction strategy to clone the switch regions of the human myeloma U266 and of two IgE-producing human cell lines generated by treatment of lymphocytes with EBV plus IL-4. The switch junction of one of the EBV lines is a complex rearrangement in which a fragment of S gamma is interposed between S mu and S epsilon. This finding suggested that the switch to epsilon in this human lymphoid cell was preceded by a S mu-S gamma recombination. To determine whether this sequential switch rearrangement represented a unique event or occurred with some regularity in human B cells switching to IgE production, DNA samples from bulk cultures of lymphocytes treated with IL-4 were subjected to polymerase chain reaction amplification of their S mu-S epsilon junctions. When the resulting fragments were examined by Southern blotting, a substantial fraction hybridized to an S gamma probe. This finding suggests that sequential recombination involving S gamma is not rare in the switch to epsilon production in humans. Our polymerase chain reaction strategy should be useful in studying isotype switching at the DNA level.
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PMID:Ig mu-epsilon isotype switch in IL-4-treated human B lymphoblastoid cells. Evidence for a sequential switch. 132 50

The expression of HLA class II molecules is mainly regulated transcriptionally and this regulation is thought to play an important role to the control of immune response. In this report, we have studied the effect of adenylate cyclase activator, forskolin, to the expression of HLA class II molecules on the cell surface of an human multiple myeloma cell line, RPMI8226. On the northern blot analysis and FACS analysis, we have revealed that forskolin upregulated the expression of mRNAs of DQB and DRB gene and their products on its surface. On the sequence analysis of upstream of HLA-DQB gene, we have identified not only Y-,X-, W-box, which were thought to regulatory region of truncated gene, but also cAMP responsible element (CRE) like regulatory region, which located upstream of W-box. On the gel retardation assay, when we used DNA probes that were specific for CRE like region and Y-box, we have found newly detectable bands, which appeared by forskolin treatment. These data suggest that forskolin upregulates HLA class II molecules by means of the interaction between CRE and cAMP responsible element binding protein (CREB).
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PMID:[Analysis of the regulation of HLA class II genes by forskolin]. 132 79

Mouse hybridoma clones were examined for their ability to support replication of herpes simplex virus (HSV). Infection of hybridoma clone 1 cells producing an antibody not specific for HSV resulted in a persistent infection with a continuous production of infectious virus, whereas infection of the parental myeloma cells X63-Ag8.653 led to an abundant virus production and extinction of the culture. In contrast, infection of hybridoma cells producing HSV-specific antibodies was restricted to a few weeks. Infectious virus was isolated for a maximum of 10 days and, afterwards, viral antigens were detected by immunofluorescence for a maximum of 18 days. The neutralizing capacity of the antibodies was not essential since the pattern of infection in clone III E8 cells, producing a non-neutralizing antibody, did not differ from that observed in clones 2c and VI A6, which produced highly and weakly neutralizing antibodies, respectively. After loss of viral antigen, HSV DNA was no longer detected by Southern blot hybridization in hybridoma clone 2c cells. Since no difference other than the specificity of the produced antibodies is suspected between the hybridoma clones, the results suggest that the presence of HSV-specific antibodies in the B-lymphoid cell cultures is responsible for virus elimination from the cells.
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PMID:Herpes simplex virus-specific hybridoma cells cannot be persistently infected with this virus. 133 Sep 72

3T3 mouse embryo fibroblast cell growth was inhibited in a concentration dependent manner by 2',3'-dideoxycytidine (ddCyd), a strong inhibitor of human immunodeficiency virus. Cell growth inhibition was associated with an increased incorporation of ddCyd into cell DNA. In contrast SP2/0-Ag14 (a mouse myeloma) cell growth is not inhibited by 100 microM ddCyd both in the presence or absence of hypoxanthine and thymidine. Furthermore, in vitro spleen cell proliferation, upon phytohemagglutinin (PHA) addition, was much more affected by ddCyd in C57BL/6 mice than in Swiss albino mice. That indeed ddCyd affects spleen cell proliferation was confirmed by studies on splenocytes obtained from C57BL/6 mice that received ddCyd for 2 weeks in drinking water. These results suggest that ddCyd toxicity in mice is cell and strain dependent and that the toxicity mechanism is related to the incorporation of the drug in cell DNA.
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PMID:In vitro and in vivo toxicity of 2',3'-dideoxycytidine in mice. 133 13

Progress in human cell culture research is discussed based primarily on our hematopoietic cell culture studies. The article includes a historical background of Burkitt lymphoma cell lines, discovery of EBV, normal B-lymphoblastoid cell lines with EBV, a variety of leukemia, lymphoma, and myeloma cell lines, clinical and theoretical contributions made by studies of T-cell leukemia cell lines, the discovery and clinical relevance of HTLV, HIV and HBLV, early attempts at adoptive immunotherapy of patients with cancer, and the future of human cell culture research. Despite the fact that current cell culture methods permit maintenance of only limited cell types of both normal and malignant origins, biotechnological advances such as hybridoma and recombinant DNA technologies should continue to provide unlimited research opportunities in all fields.
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PMID:Historical progress and the future of human cell culture research. 133 5

Expression of CAMPATH-1H, a humanized MoAb directed against an abundant surface antigen on human lymphocytes, has been studied using transfected myeloma cells. As the site of chromosome integration of DNA transfected into a cell is random we investigated the feasibility and frequency of hitting a 'jackpot' site for expression after co-transfection with CAMPATH-1H heavy and light chain constructs in genomic context. A cell line generating 40 micrograms/ml of CAMPATH-1H in spent culture supernatant was achieved. The full nucleotide sequence of the CAMPATH-1H heavy and light chain cDNA clones is also shown, in addition a comparison of the effector mechanisms, antibody dependent cellular cytotoxicity and complement dependent cytotoxicity, of myeloma cell and Chinese hamster ovary (CHO) cell-derived CAMPATH-1H is reported.
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PMID:Humanized monoclonal antibody CAMPATH-1H: myeloma cell expression of genomic constructs, nucleotide sequence of cDNA constructs and comparison of effector mechanisms of myeloma and Chinese hamster ovary cell-derived material. 133 22


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