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)

The study was prompted by the apparent detection of insulin antibodies in a black patient with HCC and recurrent hypoglycemia who had never received insulin. It consisted of two parts. Initially the sera of 30 individuals (six normoglycemic HCC patients, three with HCC and recurrent hypoglycemia, 11 patients with noncancerous liver diseases, and 10 healthy black controls) were analyzed for the presence of insulin (and glucagon) antibodies by precipitating the bound, labeled hormone with ethanol and also by the technique of radioimmunoelectrophoresis. In the nine HCC patients, binding of 125I-insulin averaged 13% by ethanol separation and 0.018 mU/ml with radioimmunoelectrophoresis, levels that were similar to those of patients with noncancerous liver disease and significantly higher than those of the healthy controls. Mean binding of 125I-glucagon was 11% in HCC sera. Serum binding of labeled hormones correlated significantly with IgG concentrations in the patients. The second part of the study attempted to define the nature of insulin binding in HCC and other forms of liver disease. After confirmation of the increased serum binding of labeled insulin by another method of precipitation, PEG, an attempt was made to compete with the labeled insulin for its serum binding sites by adding a large amount of unlabeled insulin. This binding was not displaceable, however, and was therefore considered nonspecific. When the same procedures were repeated using normal serum to which increasing amounts of gamma globulin were added, the nonspecific binding of insulin increased in a linear fashion. Furthermore, a similar degree of high nonspecific insulin binding occurred in six patients with multiple myeloma and raised serum IgG concentrations. We therefore conclude that in the many clinical situations where hypergammaglobulinemia exists, false positive tests for the detection of antibodies against insulin (and probably other peptide hormones) will emerge unless appropriate methods are used to check for nonspecific peptide binding.
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PMID:Nonspecific blinding of insulin to gamma globulin in the serum of black patients with hepatocellular carcinoma and other forms of liver disease. 618 Jan 12

We have produced several monoclonal antibodies which appear to be directed against different antigenic determinants of rat plasma fibronectin. Fibronectin was purified from rat plasma by affinity chromatography on gelatin-Sepharose and arginine-Sepharose columns. Mice were immunized and hybridomas were prepared by fusing spleen cells with Sp2/0-Ag14 myeloma cells using poly(ethylene glycol). Three hybridomas (RFN1, RFN2 and RFN3) were selected for characterization. All are IgG molecules, one is IgG2a, one IgG2b and one IgG1. Titers of ascites fluids produced using these hybridomas range from 102 400 to greater than 409 600. The antibodies cross-reacted to different degrees with human fibronectin. Rat fibronectin was radioactively labeled and cleaved using human polymorphonuclear leukocyte elastase. Four major peptides, Mr approx. 160 000, 140 000, 60 000 and 30 000 were produced. Each of the hybridoma antibodies immunoprecipitated different elastase peptides. RFN1 precipitated the Mr 160 000 peptide, RFN2 precipitated the Mr 160 000 and the Mr 140 000 peptide and RFN3 precipitated the Mr 60 000 peptide as well as low molecular weight material migrating at the buffer front. These antibodies will be useful in studies of structure/function relationships of rat fibronectin.
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PMID:Production and preliminary characterization of monoclonal antibodies to rat plasma fibronectin. 618 52

Monoclonal antibodies specific for herpes simplex virus type 1 (HSV-1) glycoproteins were used to demonstrate that HSV undergoes mutagen-induced and spontaneous antigenic variation. Hybridomas were produced by polyethylene glycol-mediated fusion of P3-X63-Ag8.653 myeloma cells with spleen cells from BALB/c mice infected with HSV-1 (strain KOS). Hybrid clones were screened for production of HSV-specific neutralizing antibody. The glycoprotein specificities of the antibodies were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of immunoprecipitates of radiolabeled infected-cell extracts. Seven hybridomas producing antibodies specific for gC, one for gB, and one for gD were characterized. All antibodies neutralized HSV-1 but not HSV-2. Two antibodies, one specific for gB and one specific for gC, were used to select viral variants resistant to neutralization by monoclonal antibody plus complement. Selections were made from untreated and bromodeoxyuridine- and nitrosoguanidine-mutagenized stocks of a plaque-purified isolate of strain KOS. After neutralization with monoclonal antibody plus complement, surviving virus was plaque purified by plating at limiting dilution and tested for resistance to neutralization with the selecting antibody. The frequency of neutralization-resistant antigenic variants selected with monoclonal antibody ranged from 4 X 10(-4) in nonmutagenized stocks to 1 X 10(-2) in mutagenized stocks. Four gC and four gB antigenic variants were isolated. Two variants resistant to neutralization by gC-specific antibodies failed to express gC, accounting for their resistant phenotype. The two other gC antigenic variants and the four gB variants expressed antigenically altered glycoproteins and were designated monoclonal-antibody-resistant, mar, mutants. The two mar C mutants were tested for resistance to neutralization with a panel of seven gC-specific monoclonal antibodies. The resulting patterns of resistance provided evidence for at least two antigenic sites on glycoprotein gC.
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PMID:Antigenic variants of herpes simplex virus selected with glycoprotein-specific monoclonal antibodies. 618 35

Somatic cell hybrids which produced antibodies against HBsAg were established by fusing the splenocytes of BALB/c mice immunized with purified HBsAg and the myeloma cell line P3X63Ag8 using polyethylene glycol 1,000. Mouse ascites were obtained by inoculating 13 hybridoma clones, and 8 of them produced high PHA titer antibodies of 10(2) to 10(6) against HBsAg. These antibodies in ascites were analysed by way of Sephadex G-200 gel filtration, micro-Ouchterlony method and 2ME, DTT treatment. According to these analyses, one of these antibodies has belonged to IgM and the other 7 to IgG. By RPHA titration using tannic acid-treated SRBC coated with these antibodies, it was suggested that 2 clonal antibodies were against the common antigenic components of HBs subtypes and the other 5 against the component r. According to the results of RPHA test and PHA suppression test using these clonal antibodies and 116 samples of HBsAg positive sera in Hokkaido, one subtype of HBsAg was further classified into several groups. These antibodies will be valuable for many virological and serological investigation, for instance, for the detailed antigenic analyses of HBsAg and for searching a source of HBs infection containing feto-maternal infection.
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PMID:[Characterization and analysis of antibodies against HBsAg produced by somatic cell hybrids]. 619 Jul 25

Hybrid cells producing monoclonal antibodies against the O-antigens of Shigella flexneri were obtained by polyethylene glycol-mediated fusion of myeloma cells and lymphocytes from BALB/c mice immunized with whole heat-killed S. flexneri bacteria of serotypes 2a and 2b. Clones were selected for their binding specificity to structurally defined S. flexneri lipopolysaccharides (LPS). The following three groups were identified as recognizing three different epitopes: monoclonal antibodies binding to (i) S. flexneri LPS with the II:3,4 antigens, (ii) S. flexneri LPS with the II:3,4 antigens and the II:7,8 antigens, and (iii) S. flexneri LPS with the 7,8 group antigen only. Of cloned and characterized antibodies, more than 90% had either the mu or gamma 3 heavy chain and 98% had the kappa light chain. The exquisite specificity of each monoclonal antibody preparation was in complete contrast to the polyclonal specificities seen in sera from immunized rabbits. Even absorbed rabbit S. flexneri typing sera contained antibodies reacting with several different LPS, i.e., they were not type antigen specific. Ascites from immunoglobulin G monoclonal antibody preparations representing the three different specificities were used for sensitizing Staphylococcus aureus Cowan 1 bacteria and were used in coagglutination. In testing 211 clinical isolates of all different serotypes of S. flexneri, the reagents were shown to be sensitive and specific in correctly identifying all S. flexneri II and 7,8 antigen-containing strains with no false positives. Two isolated immunoglobulin M antibody clones specific for the II:3,4 and 7,8 antigens were used as successfully for identification by direct slide agglutination. These results suggest that the monoclonal reagents are superior to conventional typing antisera.
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PMID:Monoclonal antibodies specific for O-antigenic polysaccharides of Shigella flexneri: clones binding to II, II:3,4, and 7,8 epitopes. 619 76

Mouse monoclonal antibodies to various human epidermal and basement membrane components were formed by immunizing Balb/c mice with ME-180, a line of human cervical carcinoma cells. The spleen cells from hyperimmunized mice were fused with a nonsecreting mouse myeloma cell line using polyethylene glycol. The resulting hybrids were selected by growth in media containing 20% fetal calf serum, hypoxanthine, thymidine, and methotrexate in RPMI-1640 in 24-well Linbro plates. Wells producing antibodies of interest were grown and eventually cloned over an HGPRT- rat fibroblast feeder layer. These cultures were expanded and recloned. Two cloned antibodies of interest are DUX 5.2 and DUX 1.1.3. DUX 5.2 is the mouse IgG1 subclass and reacts with the membranes of ME-180 cells and the human skin epidermal basement membrane zone as shown by direct immunofluorescent microscopy. Ultrastructural localization using electron microscopic immunoperoxidase techniques showed localization of the DUX 5.2 antigen to be beneath the lamina densa; the reaction product may include the anchoring fibrils. Although DUX 5.2 reacts with the normal human basement membrane zone and the basement membrane zone in several diseases, there is no reactivity in the normal, never-blistered skin of patients with dystrophic epidermolysis bullosa (DEB). This suggests that the increased collagenase in the disease may be destroying antigenicity of the antigen recognized by DUX 5.2 or that the antigen may not be present in DEB. This antibody will thus allow early neonatal and prenatal diagnosis in DEB and allow isolation of the structural moiety which is deficient in DEB. DUX 1.1 is an IgM mouse immunoglobulin specific for the cytoplasm of human basal cells. Its reactivity with upper epidermis is significantly less than that seen in the basal layer. All cells of the basal layer stain uniformly. The slight amount of staining in upper cells probably represents dilution of antigen which is not synthesized beyond the basal layer. Basal cells of hair follicles and sweat glands are stained to some degree.
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PMID:Monoclonal antibodies to normal and abnormal epithelial antigens. 619 49

Hybridomas producing antibodies to determinants associated with the lipopolysaccharide (LPS) of Brucella abortus and B melitensis were obtained by polyethylene glycol fusion of the SP2/0 myeloma cell line with B lymphocytes harvested from a Sprague-Dawley-derived rat previously immunized with whole B abortus strain 1119 organisms. Two clones, BRU38 and BRU28 , were selected for their ability to react with whole B abortus organisms and purified smooth-LPS ( f5p ). The BRU38 monoclonal antibodies were absorbed with live, rough strain 45/20 and smooth strains of B abortus and B melitensis organisms, whereas only smooth strains absorbed the antibody activity from BRU28 . Complete inhibition of the monoclonal's activity could be achieved with crude smooth-LPS, a purified f5p fraction, and a water-soluble acid degraded polysaccharide. Absorption of BRU38 and BRU28 with rough Brucella LPS, polysaccharide-B antigen, keto- deoxyoctanoic acid, or with several sugars and fatty acids known to be components of the Brucella LPS complex had no effect on the monoclonals. The data indicate that antigenic determinants are associated with the smooth LPS complex, probably with the O-side chain, and are expressed patchwise and in different quantities on several strains of B abortus and B melitensis. The B abortus rough strain 45/20 contains surface determinants which lead to the agglutination of smooth strain 1119 organisms. The potential use of monoclonals in competitive enzyme-linked immunosorbent assays for diagnostic purposes is discussed.
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PMID:Monoclonal antibodies to Brucella surface antigens associated with the smooth lipopolysaccharide complex. 620 43

A monoclonal antibody which recognizes the [125I]human GH ([125I]hGH)-binding proteins of rabbit liver has been produced using hybridoma technology. A CB6F1/J mouse was immunized over a period of 82 days with a partially purified GH receptor (GHr) preparation. On the 83rd day, spleen cells from the mouse were fused with P3x20 mouse myeloma cells using polyethylene glycol 1540. Hydridomas were produced by selection in hypoxanthine, aminopterin, and thymidine in RPMI/1640 medium and screened for antibody production using a binding inhibition assay. Four antibody-secreting clones were isolated from the same primary well, and one of these was injected ip into mice to generate ascitic fluid. At a concentration of 1:10,000, the ascitic fluid inhibited 50% of the specific binding of [125I]hGH to rabbit liver GHr, and at higher concentrations, the ascitic fluid was capable of inhibiting 95% of the specific binding. The ascitic fluid does not bind [125I]hGH nor does it inhibit [125I]hGH binding to rat liver membranes, rabbit mammary gland, or IM9 lymphocytes. More than 90% of the antibody activity was abolished by goat antimouse immunoglobulin G antiserum. An immunoglobulin fraction from the ascitic fluid, precipitated by ammonium sulfate and coupled to activated CH Sepharose, specifically adsorbed an [125I]hGH binding moiety from Triton X-100-solubilized rabbit liver membranes. After dissociation by brief exposure to 0.1 M glycine (pH 2.0), the moiety retained hGH-binding activity. Preliminary experiments indicate that the antibody will be helpful in purification of the rabbit liver GH receptor.
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PMID:A monoclonal antibody to the growth hormone receptor of rabbit liver membranes. 630 60

The establishment of functional human cytotoxic T lymphocyte (CTL) hybrids was investigated. Human CTL, generated in a seven-day, one-way mixed lymphocyte-tumor cell interaction (MLTI) against an allogeneic melanoma cell line (DW) in the presence of a third-party helper cell line and crude interleukin 2 (IL2), were fused with a mouse myeloma cell line (P3-X63 Ag8). Following fusion in polyethylene glycol, the hybrids were examined for cytotoxic potential against the sensitizing target cells DW. Hybrids with detectable levels of cytotoxicity were cloned in soft agar. Two clones demonstrating stable activity were selected for analysis of lineage and specificity of cytotoxicity. Both clones expressed cytotoxicity in a reasonable stable manner without dependence on IL2 for growth or function. Interferon had no effect on the cytotoxicity of the hybrids against the natural killer (NK)-sensitive target cells K562 or the DW cells. The cytotoxic activities of the hybrids against the sensitizing target cells DW, however, could be markedly facilitated in the presence of IL2-containing supernatants in the assay medium and less so in the presence of lectin. The range of the cytotoxic activities of the two clones was identical and restricted to the DW cells and another melanoma cell line, suggesting the possibility of a shared target molecule(s) between these two target cells for these cytotoxic hybrids. These observations indicate that the hybrids might require a mediator present in IL2 supernatant for optimum expression of cytotoxicity and suggest that the hybrids express the cytotoxic specificity of the hybridized CTL. These hybrids offer unique opportunities for critical examination of the molecular mechanisms of cellular cytotoxicity and specificities exhibited by activated human CTL.
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PMID:Functional hybrids between human cytotoxic T and mouse myeloma cells. 633 59

Serum beta 2m binding activity (S beta 2m-BA) was determined by a polyethylene glycol exclusion test of radiolabeled human beta 2m in 185 serum samples from 62 patients with multiple myeloma (MM). Elevated S beta 2m-BA was found in more than half of the samples from IgG myeloma taken before treatment or during progression of the disease but not during the plateau-phase. Conversely, elevated S beta 2m-BA was found in only one case of IgA myeloma, one case of monoclonal gammopathy of undetermined significance and none of the Bence Jones myelomas. S beta 2m-BA appears to be related to disease progression in IgG myeloma. The activity is supported by minute amounts of serum autoantibodies which are distinct from the monoclonal component. S beta 2m-BA was independent from serum beta 2m levels.
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PMID:Serum beta-2-microglobulin binding activity in monoclonal gammopathy: correlative study and clinical significance. 635 77


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