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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine Monoclonal antibodies (MAbs) to the rat brain somatostatin (SRIF) receptor were produced. Sp 2/0 myeloma cells were fused with splenocytes of Balb/c mice immunized with the soluble rat brain SRIF receptor which was partially purified by gel-filtration chromatography. Screening by radioligand ([125I-Tyr11]SRIF-14) binding inhibition assay yielded three stable cell lines producing IgG1, IgM, or IgA antibody. Autoradiographic study of the polyacrylamide gel electrophoresed under nondenaturing conditions revealed that these MAbs inhibited the ligand binding to the receptor, regardless of their incubation with the receptor prior to the ligand binding. The results suggest that the MAbs produced are the antibodies to the ligand binding site of the receptor, and bind to the receptor in competition with the ligand.
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PMID:Monoclonal antibodies to somatostatin receptor of rat brain. 129 56

Novel islet cell, duct cell, and acinar cell markers have been identified by monoclonal autoantibodies (Maab) derived from prediabetic BB rats. Spleen cells from two rats that both developed diabetes after splenectomy were fused with mouse myeloma cells. A cellular immunoradiometric assay for differential reactivity toward the surface of two closely related, insulin- and non-insulin-producing rat islet tumor cell lines was used to select and clone several IgM-producing hybridomas. The supernatants were finally characterized by two-color immunofluorescence with islet hormone antisera on frozen sections of human, monkey, and rat pancreas. Maab EB52 stained PP cells, but also few A cells on rat pancreas. Maab CA812 identified a subpopulation of islet D cells on rat, human and monkey pancreas. Although the CA812-reactive antigen and somatostatin were coexpressed in most D cells in adult rat pancreas, only a few islet D cells were stained in the newborn pancreas. The CA812-reactive antigen was not detected in somatostatin-producing cells in the duct epithelium. Maab H37 and IF5 selectively stained acinar cells in rat, human, and monkey pancreas, whereas Maab DA39 identified the rat ductal epithelium including the scattered endocrine cells of the ducts. In summary, B lymphocytes producing autoantibodies to pancreatic endocrine, exocrine, and ductal markers are present in prediabetic BB rats and can be detected by use of transformed pluripotent islet cells as target. Such B lymphocytes can be immortalized to produce monoclonal antibodies to study their role in insulin-dependent diabetes mellitus pathogenesis and to clarify the development of the pancreas.
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PMID:Novel islet, duct, and acinar cell markers defined by monoclonal autoantibodies from prediabetic BB rats. 212 46

An unlimited supply of suitable antisera is wanted for immunoassays, analysis of antigenic determinants and precise localization of antigens in biological systems. Therefore, we produced a monoclonal antiporcine insulin antibody by the hybridoma technology and assessed it in comparison with polyclonal antibody. The spleen cells of BALB/c mice immunized against porcine insulin were hybridized with mouse myeloma cells (P3-X63-Ag8-U1). The monoclonal antibody thus generated was shown to have high binding capacity and specificity to porcine insulin in radioimmunoassay. It reacted with human insulin as well, but did not crossreact with other polypeptide hormones produced in the pancreatic islets such as glucagon, somatostatin and pancreatic polypeptide. In immunohistochemistry human and dog islets were stained by this monoclonal antibody. Rat islets were not stained, although they reacted with polyclonal anti-insulin antibody. The insulin of human serum samples measured using the monoclonal antibody was tightly correlated with that using the polyclonal antibody. These observations indicate that our hybridoma-derived monoclonal antibody is useful for immunoassay as well as localization of insulin.
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PMID:Production of anti-insulin monoclonal antibody and its application to immunoassay of insulin and immunohistochemistry. 246 89

Somatostatin (SOM) is a neuroendocrine tetradecapeptide that suppresses specific functions of differentiated T-cells and antibody-producing cells. The Jurkat line of human leukemic T-cells and U266 IgE-producing human myeloma cells bound [I-Tyr11]SOM specifically. The maximal level of specific binding was attained by 1-2 h at 22 degrees C for both types of cells and reversed by 70-85% within 2-3 h after the addition of excess nonradioactive SOM. Computer-assisted Scatchard analysis of the competition curves revealed two classes of binding sites for both cells. An average of 144 and 1295 high affinity receptors per Jurkat and U266 cells had a Kd value of 3 pM and 5 pM, respectively, whereas a large number of low affinity sites had Kd values of 66 nM and 100 nM. The affinity of the analogs somatostatin 28, [I-Tyr11]SOM, and [D-Trp8, D-Cys14]SOM for Jurkat and U266 cell lines, relative to SOM, suggested a degree of specificity similar to receptors on neuroendocrine cells.
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PMID:Distinct subsets of somatostatin receptors on cultured human lymphocytes. 256 57

Hybridoma-produced monoclonal antibody (MoAb) against insulin is useful for insulin assays because of its specificity and plentiful supply. The spleen cells of male BALB/c mice immunized against monocomponent porcine insulin were hybridized with mouse myeloma cells (P3-X63-Ag8-U1). The resulting anti-insulin antibody (Ab) was purified and characterized by radioimmunoassay (RIA) using 125I-porcine insulin and sandwich-method enzyme immunoassay (EIA) using Ab-conjugated beads and beta-galactosidase. For reference, we used anti-insulin polyclonal antibody raised in guinea pigs (PoAb). Using the Ouchterlony technique, we identified the antibody as being of subclass IgG 1. We judged this antibody to be MoAb because it did not react at all with porcine insulin during EIA, in concentrations between 0 and 12.5 ng/ml; in contrast, PoAb reacted dose-dependently. During RIA, this Ab did not cross-react with glucagon, somatostatin or pancreatic polypeptide. It did cross-react with human and bovine insulins but not with rat insulin. The proper concentration of this MoAb for RIA proved to be 1:1,500,000 and the smallest detectable level of porcine insulin by RIA using this Ab was 0.5 ng/ml. These levels were similar to those obtained with PoAb. The binding activity of this MoAb to human insulin was quite similar to that of porcine insulin. RIA insulin determinations using our MoAb correlated well with those employing PoAb.
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PMID:Production of anti-insulin monoclonal antibody and its clinical application. 268 Mar 69

The antiprotozoal drug pentamidine can be toxic to islet cells in vivo and in vitro. Rat islets were exposed to pentamidine (mesylate and isethionate salts) and six other structurally related diamidines. The beta-cell response to arginine + theophylline was suppressed by pentamidine (10(-2) mmol/l) while the glucagon and somatostatin secretions persisted. All diamidines tested suppressed the beta-cell function, with a log-dose-response proportionality, the mesylate compound being more potent than pentamidine isethionate, and the lipophilic analogs more than the hydrosoluble diamidines. Electron microscopy revealed distinct morphological alterations in islets exposed to pentamidine, the intensity of these changes being dose-and time-dependent, and the beta cells more severely damaged than the non-beta cells. 51Cr-labelled islet cells and RIN 5 F cells consistently appeared more sensitive to pentamidine cytotoxicity than rat fibroblasts, myeloma cells and hepatocytes. The pentamidine-induced suppression of beta-cell function was not, in conditions tested, affected by the presence of nicotinamide and the hexose concentration in the medium. The kinetics of islet damage were slower than those of streptozotocin and alloxan-induced islet damage. The present study confirms that pentamidine is selectively toxic to islet beta cells, with some features distinct from the alloxan and streptozotocin toxicities to these cells. The mechanism of this process and its precipitating factors in vivo need clarification.
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PMID:Functional and morphological modifications induced in rat islets by pentamidine and other diamidines in vitro. 389 20

Paired staining with the unlabeled antibody peroxidase-antiperoxidase (PAP) method and direct immunofluorescence (DIF) differentiated distinctly between gastrin- and somatostatin-producing cells in the human gastric antrum. Similar paired staining of complexed lambda and alpha chains in immunoglobulin (Ig)A myeloma cells, of kappa and free J chains in IgG myeloma cells, and of secretory IgA and its epithelial transport protein, the free secretory component (SC), in colonic crypt cells, demonstrated that PAP staining inhibits subsequent DIF staining of an antigenic determinant present on the same molecule as the antigen revealed by the brown color of diaminobenzidine (DAB) or present or an unassociated molecule in the same cell. A quenching effect of the DAB reaction product was noted for both fluorescein (green) and rhodamine (red) emissions. In addition, a blocking effect of the DAB deposits has been demonstrated and is assumed to be the principal methodological basis for the paired PAP-DIF staining approach omitting intermediate antibody elution, as well as for the more time-consuming sequential PAP staining with DAB substrate for the first and 4-chloro-1-naphthol (CN) for the second antigen. The quenching and blocking effects limit in practice the paired PAP-DIF method to the localization of antigens present in separate cells.
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PMID:Unlabeled antibody peroxidase-antiperoxidase method combined with direct immunofluorescence. 611 18

A normal antibody-producing cell only expresses one antibody, resulting in the well-known phenomenon of allelic exclusion. When two myeloma cells are fused, the derived hybrids are capable of co-dominantly expressing the antibody genes of both parents. Although the respective variable (V) and constant (C) region genes remain expressed in the same cis configuration, heavy and light chains of both parents are scrambled, and hybrid molecules are formed. The same is true when a myeloma and an antibody-producing cell are fused to produce a hybrid myeloma (hybridoma). Fusion therefore allows the production of hybrid immunoglobulin molecules containing two different combining sites. Hybrid molecules of this type retain antigen-binding activity and specificity. Bispecific monoclonal antibodies secreted by hybridomas may have a variety of uses in biology and in medicine. Here we have focused on their application in histochemistry. As an example, we have prepared and tested an anti-somatostatin-anti-peroxidase bispecific antibody. This way of producing hybrid molecules is superior to the production of hybrid antibodies by chemical reconstitution methods because the drastic treatment required for chain separation in the latter is likely to lead to some protein denaturation and loss of antibody activity. Intracellularly synthesized and assembled hybrids do not suffer from this disadvantage. In addition, the recombination of heavy and light chains from different antibody molecules is likely to lead to considerable waste.
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PMID:Hybrid hybridomas and their use in immunohistochemistry. 613 72

The release of mediators from unpurified human basophils challenged with anti-human myeloma IgE serum was suppressed significantly by somatostatin at respective concentrations of 3 x 10(-13) M to 10(-9) M for histamine and 10(-13) M to 10(-11) M for leukotriene D4, which had no effect on release elicited by ionophore A23187. A direct effect of picomole-nanomole concentrations of somatostatin on basophils predominated, as shown by the significant inhibition of immunologically stimulated mediator release from monocyte-free human basophils of 15 to 32% purity and from rat basophil leukemia cells. The dependence of basophil inhibition on the conformation of somatostatin was suggested by the lower potency of reduced and alkylated somatostatin and the lack of inhibitory activity of [D-Trp8] somatostatin. Somatostatin thus may mediate suppressive effects of sensory nerves in some basophil-dependent hypersensitivity reactions.
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PMID:Inhibition by somatostatin of the release of mediators from human basophils and rat leukemic basophils. 620 74

Somatostatin and its analogs can inhibit growth in several cell types, in part by interfering with insulin-like growth factor-I (IGF-I) signaling. Our previous studies point to the importance of paracrine and autocrine IGF-I in the support of growth and survival of human multiple myeloma (MM) cell lines. In this report, we have investigated the potential role of a somatostatin analog, octreotide, in regulating growth and/or survival in MM. The results show that all MM cell lines express functional somatostatin receptors (sst). The MM cell lines express the subtypes sst2, sst3, and predominantly sst5 as determined by reverse-transcriptase polymerase chain reaction and fluorescence-activated cell sorter analysis. Octreotide inhibited the growth of both the interleukin-6 (IL-6)-dependent and the IL-6-independent MM cell lines. The effect is mainly cytostatic, resulting in 25% to 45% growth inhibition, and in three of eight of the MM cell lines a weak induction of apoptosis was recorded. Our results also show that octreotide may act as an inducer of apoptosis in primary B-B4(+) plasma cells isolated from bone marrow of MM patients. In conclusion, the results show a novel pathway for growth inhibition of MM cells: the activation of somatostatin receptor signaling.
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PMID:The somatostatin analog octreotide inhibits growth of interleukin-6 (IL-6)-dependent and IL-6-independent human multiple myeloma cell lines. 1002 2


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