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)

S107, a phosphocholine-binding myeloma protein, has been cloned in soft agar, and an antigen-binding variant has been isolated and characterized. The variant does not bind phosphocholine attached to carrier or as free hapten in solution but does retain antigenic determinants (idiotypes) of the parent. Chain recombination experiments suggest that the defect in binding is entirely in the heavy chain. Amino acid sequence analysis showed a single substitution--glutamic acid to alanine at position 35--in the first hypervariable or complementarity-determining region. In terms of the three-dimensional model of the phosphocholine-binding site, glutamic acid-35 provides a hydrogen bond to tyrosine-94 of the light chain that appears to be critical for stability of this portion of the binding site. The removal of this bond and the presence of the smaller alanine side chain is thus consistent with the loss in binding activity. These results suggest that small numbers of substitutions in antibodies, such as those presumably introduced by somatic mutation, may in some situations be effective in altering antigen-binding specificity.
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PMID:Single amino acid substitution altering antigen-binding specificity. 680 47

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

Monoclonal antibodies to MDP were prepared by hybridization of NSO myeloma cells with spleen cells of BALB/c mice immunized with MDP conjugated to methyl-BSA. Hybridomas secreting anti-MDP antibodies were selected by the binding activity of their supernates to MDP-A--L using a radioimmunoassay. After cloning in soft agar, the specificities of monoclonal anti-MDP antibodies were assayed by an inhibition of ELISA with various derivatives of MDP. Fine structural analysis of specificity for one such clone (2-4) is reported. This antibody recognizes the N-acetyl-muramic acid (N-Ac-Mur) linked to the dipeptide but not N-Ac-Mur or/and dipeptide alone. The N-Ac group on muramic acid is an important antigenic determinant and the glycopeptide linkage seems to be crucial in presenting the sugar moiety. Conservative substitution of L-Ala (i.e. by L-Ser or L-Val) had no effect on the binding ability to the antibody whereas a radical change, i.e. replacement of L-Ala by L-Pro or N-methyl-L-Ala completely abolished the antigenicity of the molecule. There was no clear correlation between biological activities of various derivatives of MDP and their ability to react with this antibody. Some possible hypotheses explaining this lack of correlation are presented.
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PMID:Monoclonal antibodies to the synthetic adjuvant muramyl dipeptide: characterization of the specificity. 688 82

The L-alanine taste receptors of the channel catfish Ictalurus punctatus provide a useful biochemical model for studying taste receptor mechanisms. Mouse hybridomas that synthesize monoclonal antibodies have been produced. The antigen used to activate mouse spleen cells was the plasma membrane fraction obtained from the taste receptor-containing epithelium of the channel catfish. The spleen cells were fused with myeloma cells, Sp2/0-Ag14, to form hybridomas. To demonstrate inhibition of ligand binding by the product of these hybridomas, a catfish membrane fraction (fraction P2) was incubated with the antibody-containing preparation prior to assaying for L-[3H]alanine binding activity. We thereby demonstrated inhibition of binding of the taste ligand L-alanine to fraction P2. This approach should prove useful in further studies of receptor binding and transduction events in taste receptors.
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PMID:Biochemical studies of taste sensation: monoclonal antibody against L-alanine binding activity of catfish taste epithelium. 696 36

Three monoclonal antibodies were produced by fusing mouse myeloma cell line NS-1 with spleen cells from C3H/An mice hyperimmunized with B6-H-2k spleen cells. These antibodies recognized an alloantigen displaying a similar strain distribution pattern to the Ly-6.2 and Ala-1.2 alloantigens. Analysis of CxB and BxH recombinant inbred mice revealed close linkage of genes controlling Ly-m6 and Ly-6. The monoclonal antibodies lysed 70 percent of cells in lymph nodes and 60 percent in spleen in direct cytotoxicity assays, but did not lyse significant numbers of cells of thymus and bone marrow. Separated T and B cells were reactive with the antibodies, but T cells were more sensitive to the antibody and complement than B cells. Virtually all cells in cultures of cells activated in the mixed lymphocyte reaction or by Concanavalin A were reactive with the monoclonal antibodies. Direct plaque-forming cells were completely eliminated by the monoclonal antibody and complement. By absorption tests, cells from all organs tested so far (thymus, lymph node, spleen, bone marrow, brain, kidney and liver) were shown to express the Ly-m6 determinant. Tumor cell lines with T, B or stem cell characteristics were reactive with the monoclonal antibody by direct cytotoxicity and absorption assays.
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PMID:Studies of the mouse Ly-6 alloantigen system. I. Serological characterization of mouse Ly-6 alloantigen by monoclonal antibodies. 696 16

C3 H/He-mg mice were immunized with C57BL/10 (B10) spleen cells and the immune spleen cells were fused with BALB/c myeloma cells (NS1). One of the monoclonal antibodies (H9/25 antibody) produced by the hybrid cells was studied. It reacts with subpopulations of B10 lymphocytes as well as some lymphoid tumor lines including some of the Abelson virus-induced leukemias. The antigen recognized by H9/25 antibody is expressed on lymphocytes from all the B10 congeneic mice tested as well as some other strains of mice. No linkage between genes coding for the antigen and H-2 loci was found as judged by its presence on cells of the B10 strains regardless of H-2 type and the distribution of the antigen on Bailey recombinant inbred mice. The antigen is expressed on subpopulations of lymph node cells, spleen cells, thymocytes and bone marrow cells. The strain distribution of the H9/25 antigen seems to be identical to that of Ly-6, Ly-8 and Ala-1 antigens. However, the tissue distribution of the antigen recognized by H9/25 antibody, while similar to these alloantigens, is unique and the antigen may be distinct from the other alloantigens.
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PMID:H 9/25 monoclonal antibody recognizes a new allospecificity of mouse lymphocyte subpopulations: strain and tissue distribution. 739 56

To study the mechanism of the effects of alpha-interferon (alpha-IFN) on chronic hepatitis B, we examined its effect on hepatitis B virus (HBV)-specific cytotoxic T cells (CTL). Using two different HBV-DNA transfected human myeloma cell lines, one expressing hepatitis B core antigen (HBcAg; C4) and the other expressing hepatitis B surface antigen (HBsAg; S6) as targets in cytotoxic tests in vitro, peripheral blood mononuclear cells obtained from chronic hepatitis B patients who were treated with alpha-IFN were examined for their cytotoxic activity against these transfectants. During the treatment with alpha-IFN, in association with a decline of serum alanine amino transferase levels, CTL activities were significantly reduced. An inhibition study in vitro revealed that alpha-IFN did not directly inhibit these CTL activities, indicating that alpha-IFN may inhibit the induction of CTL, and thereby may be related to the reduction of hepatocyte injury.
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PMID:Effect of alpha-interferon on hepatitis B virus-specific cytotoxic T cells. 762 Jan 3

The effects of the glucose supply on growth and metabolism of an SP2/0 derived recombinant myeloma cell line were studied in chemostat culture during growth on IMDM medium at a fixed dilution rate of 0.032 h-1. Lowering of the feed medium glucose concentration from 25.0 to 1.4 mmol/L resulted in a decrease of steady-state viable cell concentration from 1.9 x 10(9) to 1.0 x 10(9) L-1, whereas viability remained above 90%. Mass balances indicated that only a minor amount of glucose was utilized via the TCA cycle irrespective of the glucose concentration in the feed medium. The apparent biosynthetic yield of cells from ATP was independent of the ratio between the specific glucose and glutamine consumption rate. It is concluded that the primary role of glucose is the provision of intermediates for anabolic reactions. In addition, glucose may play an indirect catabolic role in the process of glutaminolysis by providing the pyruvate for the transamination of glutamate to alanine and alpha-ketoglutarate. At low glucose concentrations in the feed medium, glutamine is probably the sole energy source for this myeloma in chemostat culture.
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PMID:Effects of glucose supply on myeloma growth and metabolism in chemostat culture. 782 30

Human gelatinase A, a member of the matrix metalloproteinase family, is secreted from cells as the M(r) 72,000 latent precursor, progelatinase A. The autolytic removal of an N-terminal propeptide generates the M(r) 66,000 active form. Mutants of recombinant progelatinase A, altered such that the proposed active site glutamic acid residue (E375) was replaced by either an aspartic acid (proE375-->D), an alanine (proE375-->A) or a glutamine (proE375-->Q), were purified from medium conditioned by transfected NS0 mouse myeloma cells. Like wild-type progelatinase A, the mutant proenzymes were inactive and could bind tissue inhibitor of metalloproteinases (TIMP)-2 but not TIMP-1 to their C-terminal domains. Their rates of autolytic processing induced by the organomercurial (4-aminophenyl) mercuric acetate, however, were markedly slower and, of the three M(r) 66,000 forms so produced, only E375-->D displayed any proteolytic activity against either a synthetic substrate (kcat/Km = 10% that of the wild-type enzyme) or denatured type I collagen (specific activity = 0.9% that of the wild-type enzyme). ProE375-->A and proE375-->Q could be more rapidly processed to their M(r) 66,000 forms by incubation with a deletion mutant of gelatinase A that has full catalytic activity but lacks the C-terminal domain [delta (418-631) gelatinase A]. These two M(r) 66,000 forms displayed low activity on a gelatin zymogram (approximately 0.01% that of the wild-type enzyme) but, like E375-->D were able to bind TIMP-1 with an affinity equal to that of the activated wild-type enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mutation of the active site glutamic acid of human gelatinase A: effects on latency, catalysis, and the binding of tissue inhibitor of metalloproteinases-1. 791 25


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