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)

Six myeloma cell hybrids producing antibodies to human beta-endorphin were isolated from a single mouse spleen. The monoclonal antibodies displayed different binding patterns with the antigen. We report the characterization of one antibody which recognizes the tetrapeptide Tyr-Gly-Gly-Phe representing the message sequence found at the NH2 terminus of all naturally occurring mammalian opioid peptides. Competition experiments in radioimmunoassay and immunohistochemistry show that the antibody fails to bind the beta-endorphin precursor beta-lipotrophin, does not discriminate among opioid peptides that share the same message sequence but have different COOH-terminal extensions, and does not react with pharmacologically inactive derivatives of beta-endorphin. The antibody recognition of the message sequence of natural opioid peptides is sensitive to those molecular changes that affect their receptor binding competence.
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PMID:Monoclonal antibody to the message sequence Tyr-Gly-Gly-Phe of opioid peptides exhibits the specificity requirements of mammalian opioid receptors. 619 29

Evidence is presented indicating that a novel DNA sequence arrangement generated by in vitro recombination may elicit high frequency transpositions of IS elements. A 109 bp Bam HI fragment of the cDNA for the immunoglobulin kappa light chain from MOPC 321 myeloma was cloned into the Bam HI site of pBR313. The cloned fragment extends from the codon for Gly 57 to the V-J junction. Insertions of IS1 or IS5 were identified in 6 of 50 plasmid DNAs isolated from freshly transformed clones. Additional transposition events were detected after subculturing for several growth cycles. Three independent insertions of IS1 occurred in the promoter region of the TcR operon. All IS5 and the remaining IS1 insertions were located in the TcR region upstream to the cloned DNA sequence. Sequences homologous to the ends of IS1, or corresponding to the consensus sequence at the target site of IS5 are present near the estimated sites of insertion of IS1 or IS5 respectively. Bacteria harboring recombinant plasmids carrying the cloned DNA in either orientation grew at a reduced rate relative to cells harboring pBR313, suggesting that fused gene products made from the two types of plasmid were inhibitory to cell growth. IS insertions, which relieved this inhibitory effect and thereby provided a selective advantage, were found exclusively in plasmids carrying the cloned DNA in only one of the two orientations. The fact that IS elements were not observed in the other type of recombinant plasmid indicates that selective pressure alone is not sufficient to account for the frequent IS insertions observed and that sequences at a distance from the site of IS insertion may be critical in the regulation of transposition frequency.
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PMID:A cloned immunoglobulin cDNA fragment enhances transposition of IS elements into recombinant plasmids. 629 Sep 84

A stable hybridoma secreting homogeneous antibody (immunoglobulin class IgG2a) has been prepared by fusion using cells of immunoglobulin non-secreter myeloma (P3X63Ag8.653) and spleen cells of mice which had previously been immunized with the NH2-terminal CNBr fragment of human fibrinogen, the so-called N-DSK [(A alpha 1-51, B beta 1-118, gamma 1-78)2]. In competitive ELISA or radioimmunoassay this antibody (MAb/1-8C6) cross-reacted with intact fibrinogen, N-DSK, a des fibrinopeptide A (des FPA) variant of N-DSK, the so-called (B)N-DSK, as well as the intact B beta chain (B beta 1-118) obtained from N-DSK. Also, and mot importantly, cross-reactivity was observed with fibrinogen-free ethanol extracts of plasma obtained from patients known to contain high levels of fibrinogen or fibrin degradation products. In vitro thrombin digestion of any of these competitors resulted in complete loss of cross-reactivity. MAb/1-8C6 did not react with the A alpha or gamma-chains of N-DSK, free fibrinopeptide B(FPB), free B beta 15-42, as well as equimolar mixtures of the latter two peptides. These results suggest that MAb/1-8C6 may be to an epitope in or around the thrombin-susceptible B beta 14 Arg-25 Gly bond. Furthermore, due to its reactivity with patient plasma extracts, this antibody may be useful in clinical investigations dealing with fibrino(geno)lysis.
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PMID:A monoclonal antibody with ability to distinguish between NH2-terminal fragments derived from fibrinogen and fibrin. 665 69

A protected tridecapeptide of the sequence Boc-Lys(2CIZ)-Arg(Tos)-Leu-Glu (OcHex)-Trp(For)-Ile-Ala-Ala-Ser(Bzl)-Arg(Tos)-Asn-Lys(2CIZ)-Gly-OH, representing residues 43-55 of the variable region of the heavy chain of mouse myeloma protein M603, was synthesized. It was assembled by a stepwise solid phase method designed to give a fully protected peptide in high yield and purity with minimal side reactions. Thus, the peptide chain was attached as an alpha-methyl phenacyl ester to a 2-bromopropionyl-resin. After the synthesis the protected peptide fragment was obtained in 89% yield by photolytic cleavage from the resin. The peptide was purified by multiple precipitation and column chromatography. It was shown to be homogeneous by reverse phase high pressure liquid chromatography, and it had the correct amino acid composition and sequence. In the course of this work it was shown that tert.-butyloxycarbonyl-amino acids caused the formation of significant amounts of pyrrolidone carboxylic acid residues during the coupling reaction when a gamma-benzyl glutamyl residue was NH2-terminal. Other weak-acid additives also caused this chain terminating side reaction. The cyclization was markedly suppressed by protection of the glutamyl side chain as a cyclohexyl ester. With this protecting group, no evidence of pyrrolidone carboxylic acid formation could be detected in the tridecapeptide 43-55.
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PMID:Solid phase synthesis of the protected 43-55 tridecapeptide of the heavy chain of myeloma immunoglobin M603, employing cyclohexyl ester protection for glutamic acid. 681 68

Four radioimmunoassays (RIA) are described for the quantitation of serum thymic factor (facteur thymique serique, FTS), a thymic peptide hormone. Each assay employs an antibody specific for FTS, synthetic FTS (Glp-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn) as the hormone standard, and a radioiodinated FTS analogue as the tracer. Since FTS lacks a tyrosine residue, 2 FTS analogues were synthesized by the solid-phase method with tyrosyl-alanyl or 3-(2,6-dichlorobenzyl)tyrosyl-alanyl in place of the amino-terminal pyroglutamyl residue (Glp). They showed full FTS immunoreactivity and their radioiodinated derivatives served as FTS tracers. Two assays used the antiserum from a rabbit immunized with an FTS-protein conjugate. Two other assays used a monoclonal antibody against FTS produced by a hybridoma derived from mouse myeloma cells and splenocytes from a BALB/c mouse immunized with an FTS-mouse IgG conjugate (Ohga et al., 1982). All 4 RIAs were specific for FTS. The more sensitive rabbit antiserum can detect as little as 1 pg of FTS in a 50 microliters sample, which may allow quantitation of the FTS circulating in human peripheral blood.
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PMID:Radioimmunoassays for the thymic hormone serum thymic factor (FTS). 682 1

In order to obtain probes suitable for the determination of the major soybean allergen, Gly m Bd 30 K, in soybean-related processed foods, we have prepared two monoclonal antibodies, F5 of IgG2a and H6 of IgM, by the fusion of P3U1 myeloma cells with the spleen cells of BALB/c mice immunized with the reductively carboxymethylated allergen (RCM-allergen). The two monoclonal antibodies were shown to be specific to the intact allergen as well as the RCM-allergen and to recognize distinct epitopes on the allergen. Of the monoclonal antibodies, F5 was conjugated with peroxidase. H6 and the labeled F5 were applied as the fixing antibody and the labeled first antibody, respectively, for a direct sandwich enzyme-linked immunosorbent assay of the allergen. When the allergen was extracted from the soybean-related foods with Tris-HCl buffer containing sodium dodecylsulfate and mercaptoethanol, the allergen, Gly m Bd 30 K, was shown to be measured in a range of 5-500 ng in this assay.
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PMID:Preparation and application of monoclonal antibodies for a sandwich enzyme-linked immunosorbent assay of the major soybean allergen, Gly m Bd 30K. 750 67

From October 1987 to November 1993 we evaluated the serum levels of ammonia and amino acids in 85 patients with multiple myeloma. Six of the 85 cases of multiple myeloma demonstrated hyperammonemia and none of the known causes of hyperammonemia, such as liver failure, could be identified in these patients. All six patients also showed serum amino acid disturbances and conscious disorders in various degrees. In this study we compared these abnormalities in multiple myeloma with those in chronic liver failure (n = 14), the basic diseases of which were liver cirrhosis in six cases and liver cirrhosis complicated hepatocellular carcinoma in eight cases. There was a marked difference in the levels of individual serum amino acids between these two groups. The level of glycine was significantly higher in the multiple myeloma group (P < 0.001); on the other hand, that of tyrosine was significantly higher in the liver failure group (P < 0.005). The histidine (P < 0.005) and arginine (P < 0.005) levels were lower in the myeloma group. The ratio of glycine to tyrosine (Gly/Tyr) was 16.7 +/- 4.85 in the myeloma group and 1.7 +/- 0.12 in the liver failure group. The ratio of glycine to tyrosine was an important criterion for differential diagnosis.
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PMID:Serum amino acid disturbance in multiple myeloma with hyperammonemia. 759 24

Human peripheral blood eosinophils adhered specifically to microtitre plates coated with plasma fibronectin (Fn) in a dose- and time-dependent fashion. Adhesion was optimal at 60 min at a concentration of 100 micrograms/ml. Adherence to Fn was up-regulated by platelet-activating factor (PAF; optimum concentration of 10(-6) M) and was significantly inhibited by a polyclonal anti-Fn antibody (P < 0.05). The following evidence suggested that eosinophil adhesion to Fn was mediated by alpha 4 beta 1: (1) eosinophil adherence to Fn was not inhibited by an Arg-Gly-Asp-Ser (RGDS) synthetic peptide; (2) there was a dose-dependent adherence of eosinophils to microtitre plates coated with the 40,000 MW proteolytic fragment of Fn that contains the CS-1 alpha 4 beta 1 binding region, whereas adherence to the 120,000 MW chymotryptic fragment of Fn, which contains the RGD-dependent binding site, was weak and only observed at high concentrations (> 250 micrograms/ml); (3) significant inhibition of eosinophil adherence to Fn was achieved by monoclonal antibodies (mAb) against the alpha chain of VLA-4 but not by a mAb against CD45 or a mouse myeloma antibody as negative controls. After adhesion to Fn, eosinophils were investigated for their capacity to release leukotriene C4 in response to stimulation with a suboptimal concentration of calcium ionophore (2 x 10(-6) M). Significant enhancement of release was detected with Fn-coated plates but not with the control bovine serum albumin (BSA) (P < 0.01). Furthermore, this enhancement was significantly inhibited by the alpha 4 beta 1 mAb HP2/1 (P < 0.05) but not by an anti-CD45 mAb. From these studies we conclude that (1) alpha 4 beta 1 (VLA-4) integrin is a major receptor for Fn on human eosinophils and (2) adhesion to Fn may prime eosinophils for mediator release during allergic inflammation.
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PMID:Adhesion to fibronectin primes eosinophils via alpha 4 beta 1 (VLA-4). 792 93

We report the production and characterization of a human monoclonal IgM (mu, kappa) antibody recognizing the HLA A1, A23 and A24 antigens. B lymphocytes obtained from a multiparous Japanese woman were transformed in vitro by Epstein-Barr virus, screened with an immune adherence assay, and fused with a murine myeloma cell line, P3-X63-Ag8.653. After subcloning by limiting dilution three times, a stable antibody-secreting hybridoma cell line, 4-35-7, was identified. The culture supernant had a titer of 1:32-64 against each of A1-, A23- and A24-positive lymphocyte panels, and showed complete correlation (r = 1.00) with the A1, A23 and A24 antigens on a lymphocyte panel of 287 unrelated, class I HLA-typed donors by the NIH cytotoxicity assay. Monoclonality of the antibody was ensured by Southern blot analysis of the human immunoglobulin heavy chain gene of 4-35-7. In view of the published data on HLA class I nucleotide sequences, the antibody may recognize an antigeneic determinant including two amino acid residues, Asp-166 and Gly-167, in the alpha 2 helix of the class I molecule that are specific for A1, A23 and A24 so far analyzed.
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PMID:A human monoclonal antibody that detects HLA-A1, A23 and A24 antigens. 836 10

Radiolabeled antibodies have shown promise for the treatment of lymphoma and for solid tumor targeting. Campath-1H is a humanized monoclonal antibody that reacts with the CD52 antigen present on human lymphoid and myeloid cells. Campath-1H is a gamma1 (G1) isotype that induces lymphopenia via an Fc-mediated mechanism(s). Isotype switches were engineered, and the resulting antibodies were expressed in NS0 mouse myeloma cells and biosynthetically radiolabeled with [35S]methionine. The forms included G1, G4, and a G4 variant that contained alanine substitutions at (EU numbering) Leu-235, Gly-237, and Glu-318. All isotypes bound antigen equivalently as assessed by target cell binding in vitro. The G4 variant had a greatly reduced capacity to interact with Fc receptor by virtue of reduced binding to THP-1 human myeloid cells and by a 1000-fold increase in EC50 to intermediate antibody-dependent cellular cytotoxicity. The pharmacokinetics of the isotypes were compared in CD-1 (nu/nu) mice bearing an experimental antigen-expressing tumor. The plasma half-life and tumor uptake were increased for the G4 variant. The G4 variant showed significantly less spleen, liver, and bone uptake but similar uptake in the lung, kidney, and stomach and lower tissue-to-blood ratios. Immunogenicity was assessed after repeated monthly administrations of unlabeled antibody in BALB/c mice. A 50% reduction in the incidence of anti-globulin response was observed for the G4 variant. These properties suggest that antibodies with reduced Fc receptor interaction merit additional study as potential targeting vehicles relative to other isotypes for radioimmunotherapy or situations where diminished normal tissue binding contributes to efficacy.
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PMID:Improved biodistribution, tumor targeting, and reduced immunogenicity in mice with a gamma 4 variant of Campath-1H. 861 27


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