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)

Mice infected with reovirus type 1 develop an autoimmune polyendocrine disease. Spleen cells from these mice were fused with myeloma cells and the culture fluids were screened by indirect immunofluorescence for autoantibodies reactive with normal mouse tissues. A large panel of cloned, stable antibody-producing hybridomas has been obtained. Fourteen of the hybridomas make autoantibodies that react with cells in the islets of Langerhans, 24 with cells in the anterior pituitary, 11 with cells in gastric mucosa, and 5 with nuclei. Except for the antibodies to nuclei, the monoclonal autoantibodies are organ-specific. Some, however, show broad cross-species reactivity, recognizing similar antigenic determinants in mouse, rat, pig, and human organs, whereas other recognize determinants only in rodent tissues. Several of the antigens recognized by these monoclonal autoantibodies have been identified as hormones (for example, glucagon, growth hormone, and insulin).
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PMID:Virus-induced autoimmunity: monoclonal antibodies that react with endocrine tissues. 630 Oct 2

Three monoclonal antibodies, designated alpha IR-1, alpha IR-2, and alpha IR-3, were prepared by fusing FO myeloma cells with spleen cells from a mouse immunized with a partially purified preparation of insulin receptors from human placenta. These antibodies were characterized by their ability to immunoprecipitate solubilized receptors labeled with 125I-insulin or 125I-somatomedin-C in the presence or absence of various concentrations of unlabeled insulin or somatomedin-C. alpha IR-1 preferentially immunoprecipitates insulin receptors and also less effectively immunoprecipitates somatomedin-C receptors, while alpha IR-2 and alph IR-3 preferentially immunoprecipitate somatomedin-C receptors, but may also weakly immunoprecipitate insulin receptors. These three monoclonal antibodies, as well as A410, a rabbit polyclonal antibody, were used to immunoprecipitate insulin and somatomedin-C receptors from solubilized human lymphoid (IM-9) cells and human placenta membranes that had been 125I-labeled with lactoperoxidase. Analysis of the immunoprecipitates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicates that both receptors are composed of alpha and beta subunits. The beta subunit of the insulin receptor (immunoprecipitated by alpha IR-1 and A410) has a slightly more rapid mobility than the corresponding subunit of the somatomedin-C receptor (immunoprecipitated by alpha IR-2 and alpha IR-3). Interestingly, the alpha subunit of the placenta somatomedin-C receptor has a slightly faster mobility than its counterpart from IM-9 cells. Immunoprecipitation of receptor that had been reduced and denatured to generate isolated subunits indicates that alpha IR-2 and alpha IR-3 interact with the alpha subunit of the somatomedin-C receptor while A410 interacts with both subunits of the insulin receptor. alpha IR-1 failed to react with reduced and denatured receptors.
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PMID:Monoclonal antibodies to receptors for insulin and somatomedin-C. 630 46

We have recently shown that human immunoglobulin G (IgG) exerts an insulin-like stimulatory effect on lipogenesis by rat and human adipocytes in vitro. Highly purified polyclonal IgGs prepared from normal subjects have stimulatory potencies similar to those of monoclonal IgGs obtained from patients with hIgG myeloma. These observations suggest that this effect is probably exerted by a nonspecific nonvariable portion of the IgG molecule. We now present data to show that the Fc moiety of the IgG molecule is responsible for the stimulatory effect of this IgG molecule. These data also provide evidence for the first time that adipocytes may have Fc receptors.
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PMID:Insulin-like stimulatory effect of Fc fragments of human immunoglobulin G on rat adipocyte lipogenesis: indirect evidence for Fc receptor on adipocytes. 633 78

Non-obese diabetic mice display a syndrome with dramatic clinical and pathological features similar to those of Type 1 (insulin-dependent) diabetes in man. Circulating autoantibodies to the surface of islet cells were demonstrated in some of these mice by a protein A radioligand assay. To produce monoclonal antibodies to islet cell surface antigens, therefore, we took the spleens of non-obese diabetic mice, transferred the spleen cells into non-immunized recipient mice, which were made immunologically incompetent by a large dose of X-irradiation, and then fused their lymphocytes with FO mouse myeloma cells. After screening the resultant hybrids, one stable hybridoma (3A4) that produced a monoclonal antibody (IgG1) specifically bound to the surface of islet cells was obtained. The purified monoclonal antibody was bound to the surface of transplantable Syrian golden hamster insulinoma cells sevenfold more than control antibody. Adsorption of the antibody on mouse spleen lymphocytes or thymocytes resulted in only a slight decrease in 125I-protein A binding to insulinoma cells. This antibody also reacted with the surface of mouse and rat islet cells, but not with that of rat spleen cells or hepatocytes. A spectrophotometric assay for peroxidase activity demonstrated that six times more peroxidase bound to insulinoma cells incubated with the antibody than to cells treated with control antibody. Furthermore, this antibody could be visually detected in the immunoenzymatic labelling of the surface of insulinoma cells. In summary, we have developed a novel method of producing monoclonal antibodies to the surface of islet cells for probing into the pathogenesis of Type 1 diabetes.
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PMID:Production of monoclonal antibodies to islet cell surface antigens using hybridization of spleen lymphocytes from non-obese diabetic mice. 637 47

Mouse monoclonal antibodies were raised against human insulin by somatic cell hybridization using the mouse myeloma line P3-X63-Ag8. Five cell lines were grown as ascites producing tumors. Insulin binding data were determined from six monoclonal antibodies by Scatchard analysis. Each anti-insulin hybridoma antibody gave a straight-line Scatchard plot confirming the homogeneity of their binding sites and their monoclonality. The equilibrium dissociation constants ranged from 2.20 X 10(-8) to 4.48 X 10(-10) mol/l. We could demonstrate positive as well as negative cooperativity of monoclonal insulin antibodies by performing insulin binding studies with defined mixtures of two different anti-insulin hybridoma antibodies.
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PMID:Monoclonal antibodies to human insulin and their antigen binding behaviour. 638 72

By fusing peripheral leukocytes from a patient with insulin-dependent diabetes with mouse myeloma cells, a heterohybridoma was isolated that, for over one year, has secreted a human monoclonal autoantibody, designated MOR-h1 (multiple organ-reactive human 1). This antibody reacts with antigens in several endocrine organs including the pituitary, thyroid, stomach, and pancreas. By double immunofluorescence, MOR-h1 was found to react specifically with growth hormone (GH)-containing cells in the anterior pituitary and, by enzyme-linked immunosorbent assay, MOR-h1 was shown to react with both natural and biosynthetic GH. Absorption experiments revealed that GH could remove the capacity of MOR-h1 to react not only with cells in the anterior pituitary, but also with cells in the thyroid, stomach, and pancreas. The demonstration with hyperimmune serum that these organs do not contain GH indicated that MOR-h1 was reacting with a different molecule(s) in these organs. By passing extracts of pituitary, thyroid, and stomach through an MOR-h1 affinity column and analyzing the eluted antigens by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a 35,000-mol wt polypeptide was isolated from each of these organs. In addition, a 21,500-mol wt polypeptide with an electrophoretic mobility identical to purified human GH was isolated from the pituitary, but not the other organs. It is concluded that MOR-h1 reacts with a 35,000-mol wt polypeptide present in the pituitary, thyroid, and stomach and that this antibody also recognizes a determinant on GH.
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PMID:Human multiple organ-reactive monoclonal autoantibody recognizes growth hormone and a 35,000-molecular weight protein. 638 71

To assess the effects of insulin on the formation of hybridomas, sheep red blood cell (SRBC) immunized spleen cells from BALB/c mice were fused with P3U1 mouse myeloma cells. After fusion, cells were grown for 2 weeks in HAT medium containing insulin (HIAT) (doses ranging between 10(-1) to 10(-9) units/ml) or HAT medium alone. The number of hybridoma colonies was found to be significantly increased in the presence of HIAT medium compared to HAT alone. In addition, the average size of the hybridoma clones was at least doubled and the cumulative colony size index per plate increased several folds. A significant rise in the number of wells containing clones secreting anti-SRBC monoclonal antibodies was again shown in the presence of HIAT compared to HAT medium alone. The maximal effect of insulin on the above biological parameters ranged between 10(-1) and 10(-4) units/ml. It is concluded that the addition of insulin to HAT medium (HIAT) enhances hybridoma formation and thus, its more frequent use may considerably expediate ongoing research efforts on the production of monoclonal antibodies.
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PMID:The addition of insulin to HAT medium (HIAT) enhances hybridoma formation. 639 29

An easy-to-perform clonogenic culture system for myeloma stem cells is presented which approaches the patient's in vivo situation more closely and therefore seems particularly well-suited for antiproliferative drug sensitivity assays. Bone marrow cells are propagated in clotted autologous or allogenic plasma that is enriched with 2-mercaptoethanol, insulin, and synthetic nucleotides and co-factors for nuclear synthesis, no feeder layer or conditioned medium is necessary. Clusters and colonies consisting of between 8 and 60 cells readily formed within 6-8 days after cloning yielding a plating efficiency between 0.12 and 2.16%. A linear relationship between the number of cells plated and colony formation was found from 10(5) through 2 X 10(6) cells plated. The successful growth rate for 65 tests from 53 patients amounted to 90.8%. Morphological and histochemical examination of the clusters revealed lymphoid cells at various stages of maturation ranging from lymphocytic and lymphoblastoid to lymphoplasmacytic and plasma cells. Tumor origin of the clones was demonstrated by immunofluorescence studies in which Ig-positive cells stained only for the heavy and light chain isotypes identical to those of the patient's serum paraprotein. Anti-idiotypic antisera confirmed the patient's specific malignant phenotype of the colonies formed. The technique of the assay is described in detail.
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PMID:A plasma clot culture system for growing and antiproliferative drug sensitivity testing of myeloma stem cells. 647 1

A hybridoma cell line secreting monoclonal antibody specific for glutathione-insulin transhydrogenase has been produced by fusing mouse myeloma cells with spleen cells from mice immunized to purified rat liver glutathione-insulin transhydrogenase. The secreted antibody isotypes were found to be: Ig gamma 1 heavy chains and kappa light chains. This monoclonal antibody has been used to screen glutathione-insulin transhydrogenase in various rat tissue extracts (liver, fat, heart, testis, spleen, lung and kidney) following separation on NaDodSO4/urea polyacrylamide disc-gel electrophoresis and electrophoretic transfer to nitrocellulose. Screening with the monoclonal antibody showed the presence of one immunoreactive protein band equal in molecular weight to that of purified rat liver GIT (Mr 53,000) in extracts of all tissues studied and a second immunoreactive protein band of lower molecular weight (Mr 49,000) in spleen and lung tissue extracts. Separation of these two proteins by HPLC using a TSK-DEAE column demonstrated that both proteins exhibit insulin degrading activity. These data indicate that GIT may occur in multiple forms in some tissues.
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PMID:Production of a monoclonal antibody directed against rat liver glutathione-insulin transhydrogenase. 651 17

Serum-free chemically defined medium for hybridoma and parental myeloma cultivation was developed on the basis of testing of individual substances supporting hybridoma growth under serum-free conditions. Optimized concentrations of transferrin, insulin, ethanolamine, linoleic acid, serum albumin, ascorbic acid, hydrocortisone, and trace elements could substitute serum. Developed serum-free hybridoma (SFH) medium differs from analogous previously described media mainly by a more complete combination of growth-supporting supplements and by the presence of ascorbic acid and hydrocortisone. Growth comparable with that in the medium supplemented with 10% bovine serum was achieved with four hybridomas and two myelomas. SFH medium was also suitable for long-term cultivation of hybridomas without cessation of monoclonal antibody production. Growth potency and the specific growth requirements of hybridomas in serum-free medium are, to a large degree, determined by parental myeloma.
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PMID:Serum-free medium for hybridoma and parental myeloma cell cultivation: a novel composition of growth-supporting substances. 672 41


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