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)

Four hybrid cell lines secreting monoclonal antibodies (McAbs) against glucosyltransferase synthesizing water-insoluble glucan (GTase-I) were generated by fusion of myeloma cells (P3U1) with splenocytes from mice immunized with GTase-I from Streptococcus sobrinus B13-N. Cell lines 29E7, 21GC7, and 42HB8 were found to secrete an IgG2a-type immunoglobulin, and 29EG, an IgM-type immunoglobulin. These two isotypes of McAbs were used for the determination of the binding sites on the GTase molecule, with use of an enzyme-linked immunosorbent assay. The binding site for McAb 29EG was different from the site that bound other McAbs. McAb 29EG was found to inhibit water-insoluble glucan synthesis by GTase-I by 50%, and 29E7 was found to inhibit it weakly. However, other McAbs did not show any inhibitory effect in spite of binding to GTase-I. McAb 42HB8 strongly inhibited GTase-I-mediated adherence of heat-killed cells of S. sobrinus B-13N to glass surfaces. When the McAbs were tested for their cross-reactivity among GTase preparations from different mutans streptococci, McAb 29EG reacted with S. cricetus and S. sobrinus, but not with other mutans streptococci. Three other McAbs, 21GC7, 29E7, and 42HB8, were found to react only with the enzyme from S. sobrinus. These findings indicated that the specificity of the McAbs studied varied with respect to the antigenic sites on the GTase-I molecule, and that some of the sites differed in their functions.
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PMID:Characterization of monoclonal antibodies against glucosyltransferase synthesizing water-insoluble glucan from Streptococcus sobrinus B13. 168 48

To elucidate the role of genetics in familial multiple myeloma, two sisters having plasma cell dyscrasia were studied. The women were 58 and 56 years old, and the diagnoses were made 22 months apart. Specific antisera for patient 1's lambda light chains produced in rabbits had no cross-reactivity with her sister's lambda light chains. Karyotypic analysis by G.T.G. banding revealed abnormalities in both patients, but no common abnormalities. HLA typing disclosed identical tissue types (AW24, A26, B13, BW55). An immunologic epidemiologic study performed on 26 family members, encompassing four generations, disclosed no additional cases of paraproteinemia.
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PMID:Genetic aspects of familial multiple myeloma. 195 37

To simplify the screening procedure for murine monoclonal antibodies specific for polymorphic HLA determinants, spleen cells from a mouse immunized with the human cell line BJAB-B95.8.6 were fused with NS1 mouse myeloma cells, and hybridoma supernatants were screened for their reactivity on BJAB-B95.8.6 and two gamma ray-induced HLA-loss mutants of this line. The use of these HLA-loss mutants allowed the rapid identification of two new allospecific MOABs designated TU160 and TU161. Serological as well as biochemical studies revealed TU160 to be specific for HLA-A2, and TU161 for HLA-B13 molecules, respectively. Both MOABs were determined to be antibodies of the IgG class and were able to precipitate their antigens from lysates of radioactively labeled cells.
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PMID:Gamma ray-induced mutants as a tool for the production and characterisation of monoclonal antibodies against HLA-alloantigens. 301 80

Monoclonal antibodies (MAbs) against HLA antigens can give better information about the serology and biochemistry of the human major histocompatibility complex (MHC) than HLA antisera obtained from pregnant women. To increase the very limited panel of MAbs against HLA we immunized mice with human cultured cell lines and fused their spleen cells with the Ag8-653 myeloma. We produced MAbs against HLA-A1, A2/w69, A2/28, A2/11/25/26/28/29/30/31/33/34, A25/32, B7/22, and B13. The best dilution medium to store the MAbs in Terasaki plates was RPMI 1640 supplemented with 7% bovine serum albumin. The MAbs are also excellent reagents to investigate public HLA antigens and to stain HLA antigens in cryosections of transplanted organs.
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PMID:Production and applications of new monoclonal antibodies against human lymphocyte antigen-A and -B antigens. 321 87

Nano- to picomolar concentrations of high affinity IgG antibody to interleukin 6 (IL-6ab) were detected in sera of 71 of 467 normal Danish blood donors (15%). IL-6 bound to the Fab fragments of IL-6ab, and the antibody specifically and competitively interfered with enzyme-linked immunosorbent assays for human IL-6. Only IL-6ab-positive sera interfered with these ELISAs. A statistically positive correlation was found between total IL-6 binding and specific IL-6 binding to serum (P < 0.0001), suggesting that IL-6ab dominates as IL-6 binding factors in normal human serum. The IL-6ab also inhibited binding of IL-6 to receptors on the human U-937 macrophage-like cell line, the human U-266 myeloma cell line and the mouse hybridoma cell line B13.29, clone B9 (B9 cells). IL-6-induced proliferation of the B9 cells was competitively inhibited by IL-6ab. We conclude that sera of normal individuals may contain appreciable levels of autoantibodies to IL-6. These IgG autoantibodies may be physiologically and pathophysiologically important because they are potent inhibitors of IL-6 in vitro.
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PMID:High-affinity IgG autoantibodies to IL-6 in sera of normal individuals are competitive inhibitors of IL-6 in vitro. 848 7

While the exact aetiology of myeloma is unknown, genetic factors feature among the potential risk factors. The HLA phenotypes in African blacks with myeloma (the commonest haematopoietic malignancy in this group) have not been characterized. The purpose of this study was to determine the HLA class I and class II phenotypes of patients with multiple myeloma and to compare the findings to an ethnically matched control group of 100 individuals. Analysis of the HLA class I and class II phenotypes in 62 myeloma patients revealed: (i) a corresponding statistically significant association with HLA B18 [odds ratio (OR) 6.3; 95% confidence interval (CI) 1.013-39.727; P < 0.005]; (ii) no statistically significant association with HLA B13, Cw2, Cw6 or the DR and DQ antigens; and (iii) a statistically significant negative (protective) association with HLA Cw7 (OR 0.4; 95% CI 0.21-0.87; P < 0.005). This study suggests that although genetic factors may play a role in the multifactorial aetiology of multiple myeloma, with the exception of HLA B18, there is no specific association between HLA types and multiple myeloma in South African blacks.
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PMID:HLA class I and class II antigens associated with multiple myeloma in southern Africa. 1218 Oct 24

The BCL-2 antagonist venetoclax is highly effective in multiple myeloma (MM) patients exhibiting the 11;14 translocation, the mechanistic basis of which is unknown. In evaluating cellular energetics and metabolism of t(11;14) and non-t(11;14) MM, we determine that venetoclax-sensitive myeloma has reduced mitochondrial respiration. Consistent with this, low electron transport chain (ETC) Complex I and Complex II activities correlate with venetoclax sensitivity. Inhibition of Complex I, using IACS-010759, an orally bioavailable Complex I inhibitor in clinical trials, as well as succinate ubiquinone reductase (SQR) activity of Complex II, using thenoyltrifluoroacetone (TTFA) or introduction of SDHC R72C mutant, independently sensitize resistant MM to venetoclax. We demonstrate that ETC inhibition increases BCL-2 dependence and the 'primed' state via the ATF4-BIM/NOXA axis. Further, SQR activity correlates with venetoclax sensitivity in patient samples irrespective of t(11;14) status. Use of SQR activity in a functional-biomarker informed manner may better select for MM patients responsive to venetoclax therapy.
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PMID:Electron transport chain activity is a predictor and target for venetoclax sensitivity in multiple myeloma. 3214 72