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)

Two alternate screening methods have enabled the detection of monoclonal antibodies with different specificities toward the lysosomal enzyme alpha-mannosidase of Dictyostelium discoideum. Spleen/myeloma hybrid cell cultures were screened for antibody production by separate assays: an indirect enzyme-linked immunoadsorbent assay (ELISA) based on the antibody binding to enzyme adsorbed on plastic, and a direct assay of the antibodies' ability to precipitate enzyme activity with fixed Staphylococcus aureus cells (Pansorbin). Fourteen stable antibody-producing cell lines resulted from a single fusion; these fell into three distinct classes based on their screening characteristics. A group of eight were positive in both assays, and these immunoprecipitated a 140,000 Mr precursor form of alpha-mannosidase in addition to the 58,000 and 60,000 Mr mature enzyme subunits from [35S]methionine-labeled total secreted protein preparations. Two of the antibodies were positive only in the immunoprecipitation assay; these failed to precipitate the 140,000 Mr precursor. The third class consisted of four antibodies that were positive only in the ELISA method. These exclusively recognized an altered conformation of the enzyme (precursor and mature forms) that was immobilized either on plastic or on nitrocellulose paper. In addition, only members of this class were able to bind to immobilized fragments of protease-treated enzyme. The implications of these findings for the general design of monoclonal antibody screenings and for the alternative structures of this enzyme are discussed.
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PMID:Functional heterogeneity of monoclonal antibodies obtained using different screening assays. 667 Jul 43

Murine alpha/beta interferon (IFN) inhibited the growth of myeloma cells in vitro. Independently of the cell growth inhibition, IFN also reduced the number of antibody secreting myeloma cells as measured by haemolytic plaque assay. The sensitivity of both MOPC 315 plasmacytoma cells and 4F4 hybridoma cells varied, though not to the same extent, depending on the dose of IFN used and the duration of exposure. Inhibition of PFC activity was observed after one day of IFN treatment while inhibition of cell growth was not detected until Day 2 of incubation. A dose of 20 u/ml IFN had no effect on the growth rate of MOPC 315 cells but with 100 u/ml the inhibition of growth was virtually complete. In contrast, an inhibition of PFC activity was observed at all the concentrations tested. The cell growth and PFC activity of 4F4 hybridoma cells, on the other hand, were both inhibited by IFN when used at concentrations as low as 1.25 u/ml. Incubation with higher concentrations of IFN resulted in a progressive reduction in cell growth and PFC activity of 4F4 cells, however to a lesser degree of inhibition compared to that observed with MOPC 315 cells. For example, although virtually 70% of MOPC 315 PFC could be inhibited by culture for two days in the presence of 100 u/ml, it was necessary to use 1,250 u/ml IFN for 4 days incubation before the similar level of PFC inhibition was achieved with 4F4 cells. IFN treatment resulted in an increase in both cellular volume and protein content and this effect was prevented when IFN was previously neutralised by a specific antiserum. IFN-treated cells also showed an inhibition in the incorporation of 3[H]-thymidine but no alteration in the rate of utilization of 35[S]-methionine, when compared with an equal number of control cells.
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PMID:Inhibition of cell division and antibody secretion by murine alpha/beta interferon: effects on plasmacytoma and hybridoma lymphoid cells. 671 13

The complete amino acid sequence of the variable region of Bence-Jones protein Mev. from a patient suffering from multiple myeloma and generalized amyloidosis is presented. The amino acid sequence of the Bence-Jones protein Mev. is related to other human kappa-immunoglobulin L-chains of subgroup I. With valine established in Position 191 of the constant region, it is of the Inv (3) allotype. Two types of the Bence-Jones protein Mev. were found, one beginning with the typical N-terminal aspartic acid, and another lacking the N-terminal tripeptide and commencing with methionine in Position 4. A unique insertion of glutamic acid after Position 95 was found in the Bence-Jones protein. This is the position where the V- and J-gene segments join. The J-region of Bence-Jones protein Mev. exhibits some marked differences to the five J-regions recently established by nucleic acid sequencing. This suggests, that there must be considerable polymorphism in human kappa-J-genes. The amyloid fibril protein from the same patient (A Mev.) has also been sequenced up to Position 27. It was found to be identical to the sequence of Bence-Jones protein Mev. commencing with aspartic acid. The molecular mass of the amyloid fibril protein was found to be between 11 000 and 12 000 Da as estimated by gelfiltration and dodecyl sulfate-polyacrylamide electrophoresis.
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PMID:Primary structure of the variable part of an amyloidogenic Bence-Jones Protein (Mev.). An unusual insertion in the third hypervariable region of a human kappa-immunoglobulin light chain. 681 13

Protein synthesis in cultured P3/X63-Ag8 mouse myeloma cells was inhibited by acute exposure to ethanol. However, the synthesis of IgGl antibody, as a percentage of total protein synthesis, increased slightly. Experiments using actinomycin D suggest that the overall inhibition of protein synthesis by ethanol occurs at the translational level. Following an L-[35S]methionine pulse, cultured P3/X63-Ag8 cells contained one light antibody polypeptide and two heavy antibody polypeptides. One of these heavy chains was shown to be the unglycosylated precursor of the other, mature molecule. Only the glycosylated polypeptide is a normal constituent of secreted IgGl antibody. The glycosylation of the immature heavy chains occurred more rapidly during a 1-hr isotopic pulse in cells exposed to ethanol (0.1 v/v % and above), than in unexposed control cells. The observed effects of ethanol on antibody glycosylation may be related to the increased susceptibility of alcoholic patients to infections. Ethanol may also affect the synthesis of other glycoproteins in myeloma cells and other tissues.
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PMID:Acute effects of ethanol on biosynthesis and glycosylation of IgGl(kappa) antibody molecules in cultured P3/X63-Ag8 myeloma cells. 681 55

Monoclonal antibodies to leucine enkephalin have been produced after fusion of mouse myeloma cells with spleen cells from hyper-immune mice. Hybrid clones 2D1 and SL1 were characterised using radioimmunoassay and an enzyme-linked immunosorbent assay. The antibody 2D1 was of low affinity and showed a maximum sensitivity of 0.1ng. The antibody binds equally well to the sulphated leucine enkephalin and to methionine enkephalin. It does not cross-react with dynorphin, methionine enkephalin-arg-phe or oxidised methionine enkephalin. The hybrid clone SL1 appears to be specific for leucine enkephalin. Preliminary immunocytochemical studies have shown that both antibodies bind specifically to leucine enkephalin in defined areas of the central nervous system.
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PMID:Monoclonal antibodies to leucine enkephalin. 687 Aug 87

Splenic lymphocytes from a Lewis rat, immunized with purified estradiol-receptor complex of calf uterine nuclei, were fused with cells of three different mouse myeloma lines (P3-X63-Ag8, P3-NSI/I-Ag4-1, and Sp2/0-Ag14) to yield hybridoma cultures, 9% of which produced antibodies to the receptor protein (estrophilin). When cloned by limiting dilution, approximately 70% of the viable cultures secreted antiestrophilin antibody. When expanded in suspension culture, three clones derived from Sp2/0-Ag14 were found to secrete rat IgG (gamma 2a class), whereas seven other clones (from all three myeloma lines) secreted IgM. Monoclonal IgG shows comparable affinity for nuclear and extranuclear receptors, whereas IgM reacts preferentially with the nuclear form. Both classes of antibody react with unoccupied as well as with occupied receptor and do not interfere with its ability to bind to estradiol. By growing IgG-secreting clones in the presence of [35S]methionine, radiolabeled monoclonal antiestrophilin has been prepared. Unlike antiestrophilin antibody previously generated in the rabbit or the goat, which crossreacts with estrogen receptors from every animal species tested, antibodies produced by the Lewis rat and by hybridomas derived from its spleen cells react specifically with estrophilin from calf tissues. These monoclonal antibodies provide reagents for the application of immunochemical techniques to study estrogen receptors in calf target tissues.
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PMID:Monoclonal antibodies to estrophilin: probes for the study of estrogen receptors. 692 10

The fusion of SP2/0 myeloma cells with spleen cells from mice immunized with Leishmania mexicana amazonensis promastigotes produced hybridoma clones. Indirect immunofluorescent antibody assay with live leishmanias showed that the monoclonal antibody 6H12 recognized only the antigens bound to the surface of L. mexicana amazonensis promastigotes. It also showed that the antibody bound to neither amastigotes of this species nor to other Leishmania species--i.e., L. braziliensis braziliensis, L. tropica, and L. donovani. Monoclonal antibodies from three other clones (4D11, 4H9, and 6A11) were found to compete with 6H12 for binding to L. mexicana promastigotes. With lysates of [35S]methionine-labeled promastigotes, all four monoclonal antibodies precipitated the same triplet set of protein bands at the approximately equal to 68,000-dalton region, whereas another monoclonal antibody (6G5) precipitated a different band at approximately equal to 90,000 daltons. During differentiation of L. mexicana amazonensis from amastigotes to promastigotes, there was a 4- to 8-fold increase above the initial level in the binding of 6H12 monoclonal antibody to leishmanias, as detected by enzyme-linked immunosorbent assay and quantitative fluorometric assay, respectively. Thus, we have demonstrated the use of monoclonal antibodies as probes for antigens that change during leishmanial differentiation.
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PMID:Surface antigenic change during differentiation of a parasitic protozoan, Leishmania mexicana: Identification by monoclonal antibodies. 696 14

MCF-7 human breast cancer cell estrophilin was purified by passing the cytosol fraction of a cell homogenate through an affinity column of estradiol linked to Sepharose by a substituted di-n-propyl sulfide bridge in the 17 alpha-position. When eluted with 50 mcM radiolabeled estradiol in 10% dimethyl formamide-.5 M sodium thiocynate, a 40% recovery of the radiolabeled estradiol-estrophilin occured along with 14% of the specific radio activity expected from the pure complex. Lewis rats immunized with this partially purified estradiol receptor complex had serum that contained antiestrophilin antibodies that reacted with nuclear and extranuclear receptor complexs from MCF-7 cells and with the estrophilin from rat, calf, and monkey uterus, hen oviduct, and other human breast cancers. Hybridoma cultures of 2 different mouse myeloma lines (P3-X63-Ag8 and Sp2/0-Ag14) yielded antibodies to estrophilin 2% of the time. After cloning, 3 hybridoma lines that secreted antiestrophilin were expanded to provide quantities of monoclonal antibodies that recognize mammalian but not avian estrophilin and that show different degrees of reactivity with receptor from nonprimate sources. by growing the clone from Sp2/0 in the presence of radiolabeled methionine, radiolabeled monoclonal immunoglobulin G was prepared and should be useful in the study of estrogen receptors in human reproductive tissues.
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PMID:Monoclonal antibodies to human estrogen receptor. 700 72

Monoclonal antibodies have been produced after fusion of NS-1 murine myeloma cells with spleen cells from mice immunized either by chronic primary infection or with irradiated cercariae: in both cases, animals were challenged with liver cercariae 7 days before fusion. The initial cultures were screened for anti-schistosomular antibodies both by a radioimmunoassay with whole schistosomulum extracts and by immunofluorescence. There was no correlation between the two techniques and subsequent screening was carried out by immunofluorescence. Cloning was carried out in soft agar and 7 cloned cell lines, from 5 initial cultures, were selected for detailed study. Products of 6 of these 7 lines were monoclonal, as judged by isoelectricfocusing of [35S]methionine-labelled supernatant fluids, and their binding to live schistosomula was specific. None of the antibodies showed detectable activity in mediating eosinophil- or complement-dependent damage to schistosomula in vitro. However, 2 antibodies were successfully used to isolate surface proteins with an apparent molecular weight of 24 000 on SDS-polyacrylamide gel electrophoresis.
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PMID:Monoclonal antibodies against surface antigens of schistosomula of Schistosoma mansoni. 706 55

The viability of neutrophils in the condition under which they kill neoplastic cells was studied. In the presence of phorbol myristate acetate (PMA) the 51Cr-release by human neutrophils was markedly stimulated. The PMA-induced 51Cr-release by neutrophils correlated well with the number of nonviable neutrophils as determined by the uptake of trypan blue. Phorbol myristate acetate had no effect on the 51Cr-release by lymphocytes, LPC-1 myeloma cells, ovarian ascites tumor cells, or neutrophils from a patient with chronic granulomatous disease. This suggests that the effect of PMA is not due to its nonspecific toxic effect; instead, it is dependent on the reactive oxygen species produced by the normal neutrophils. Catalase, cytochrome C, histidine, and methionine inhibited the PMA-induced 51Cr-release by human neutrophils, whereas superoxide dismutase, myeloperoxidase inhibitors, and some hydroxyl radical scavengers or singlet oxygen quenchers had no effect. The clumping of neutrophils induced by PMA was also important in the PMA-induced 51Cr-release by human neutrophils.
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PMID:Phorbol myristate acetate induced neutrophil autotoxicity. 719 15


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