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)

Monoclonal antibody 3A4 to islet cell surface antigen has been previously established in our laboratory, using hybridization of spleen lymphocytes from non-obese diabetic (NOD) mice transferred into immunologically incompetent recipient mice. In the present study, monoclonal islet cell surface antibody 5C12 could be newly obtained in the 10:1 ratio of NOD mice spleen cells and mouse myeloma cells (SP2/0) without any modifications. Protein A radioligand assay and indirect immunofluorescence on living cells showed that 5C12 antibody reacted to normal rat islet cells and cultured rat insulinoma cells (RIN-r), but not to cultured lymphocytes (Bri-7, IM-9) and Chang-liver cells. Analysis of 125I-labeled antibody binding revealed that unlabeled 5C12 effectively inhibited subsequent 125I-5C12 binding to RIN-r cells, whereas unlabeled 3A4 did not. The scatchard plot from these data showed the curvilinearity, and about 150,000 binding sites to antibody per RIN-r cell were counted. The treatment of RIN-r cells with papain and neuraminidase reduced the binding of 5C12 to RIN-r cells, whereas the effect of trypsin was not observed. Immunoprecipitation of 125I-labeled insulinoma cell lysates followed by SDS-PAGE and autoradiography indicated that 5C12 recognized 105K dalton cell surface protein in RIN-r cells. Immunoblotting also showed that 5C12 antibody recognized 105K dalton cell surface protein in RIN-r cells. These results demonstrated that 5C12 was an important tool for clarifying the immunoresponse against certain antigenic determinants on pancreatic B cells. Furthermore, 5C12 has not only qualitatively and quantitatively improved diagnostic methodology, but it may also provide new reagents useful to the treatment and prevention of type 1 diabetes.
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PMID:[An analysis of islet cell surface antigen defined by monoclonal islet cell surface antibody 5C12]. 354 94

The lectin-binding capacity of 96 normal human IgG, assessed by solid-phase radioimmunoassay, strikingly varied according to the lectin considered. Indeed, half of the IgG samples exhibited peanut agglutinin (PNA)- and pokeweed mitogen-specific binding capacities superior or equal to 4%, whereas less than 15% of IgG similarly bound to concanavalin A (Con A) and to phytohemagglutinin. The ability of those IgG to inhibit the Fc receptor (Fc-R) function of human monocytes, measured by a classical rosette assay, was inversely correlated to their binding ratios to PNA and Con A only. By affinity chromatography, three groups of IgG were separated: the IgG purified on agarose-PNA columns slightly reduced the Fc-R function (40-45% inhibition); the IgG purified on Sepharose-Con A columns exhibited the highest inhibitory properties (80-85% inhibition); the IgG that did not bind to PNA and Con A columns possessed intermediate inhibitory properties (65-70% inhibition). The different effect of IgG on Fc receptors was conserved when monocytes were first treated by trypsin and was unrelated to their specific binding to human monocytes, to their subclasses, and to their C1q- or protein A-binding capacities. Incubation of monocytes with D-galactose (10 mM) significantly improved their capacity to form IgG rosettes, whereas their incubation with D-mannose (10 mM) significantly reduced the Fc-R function. Scatchard plots of 125I-IgG1 myeloma protein binding to monocytes were linear under basal conditions, as well as after a prior incubation of the cells with D-galactose or D-mannose. Monocytes bound about 16,000 molecules of IgG1 per cell in each instance. In contrast, the mean association constant (Ka) for IgG1 binding was 2.59 +/- 0.50 X 10(8) M-1 under basal conditions, 4.4 +/- 0.75 X 10(8) M-1 after D-galactose incubation, and 1.35 +/- 0.50 X 10(8) M-1 after D-mannose incubation. These data suggest that the level of human monocyte Fc-R function blockade induced by human IgG depends mainly on the presence of "accessible" galactosyl or mannosyl residues in the Fc domain and that the modulation of the Fc-R function induced by these carbohydrates is due to a change in the affinity rather than in the number of single class of high-affinity binding sites.
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PMID:The spontaneous ability of normal human IgG to inhibit the Fc receptors of normal human monocytes is related to their binding capacity to lectins. 362 80

Protein A1 (Mr approximately 32,000), a major glycine-rich protein of heterogeneous nuclear ribonucleoproteins (hnRNP), was purified to near homogeneity under nondenaturing conditions from HeLa cells. Limited proteolysis of the native protein yields a trypsin-resistant N-terminal nucleic acid-binding domain about 195 amino acids long which has a primary structure nearly identical to that of the 195-amino acid-long single-stranded DNA (ssDNA)-binding protein UP1 (Mr 22,162) from calf thymus (Williams, K.R., Stone, K. L., LoPresti, M.B., Merrill, B. M., and Planck, S.R. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 5666-5670). 45 of the 61 glycine residues of A1 are present in the trypsin-sensitive C-terminal domain of the protein which contains no sequences homologous to UP1. Protein A2, another major glycine-rich core hnRNP protein from HeLa, has a domain structure analogous to A1 and appears to be related to ssDNA-binding proteins UP1-B from calf liver and HDP-1 from mouse myeloma in a way similar to the A1/UP1 relationship. In contrast to ssDNA-binding proteins, A1 binds preferentially to RNA over ssDNA and exhibits no helix-destabilizing activity.
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PMID:Purification and domain structure of core hnRNP proteins A1 and A2 and their relationship to single-stranded DNA-binding proteins. 373 53

The level of IgA-alpha 1 anti-trypsin (alpha 1 AT) complex in a relatively large number of IgA myeloma sera has been determined, and compared with their content of polymerised forms of IgA. The level of the complex was the same in sera containing only monomeric IgA, some polymer and more than 50% polymer (as determined by SDS-PAGE). There was, however, a highly significant inverse correlation between the amount of IgA-alpha 1 AT complex in the myeloma sera and their content of 10S dimer (as determined by analytical ultracentrifugation). High levels of IgA-alpha 1 AT complex were also found in the small number of myeloma sera examined which contained paraprotein of the minor allotypic form of (Am2+) of the IgA2 sub-class, indicating that the lack of disulphide bonds between the heavy and light chains of this isotype has no influence on its ability to complex with alpha 1 AT.
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PMID:Measurement of IgA-alpha 1 anti-trypsin (alpha 1 AT) complex in the sera of patients with IgA myelomatosis. 387 38

Human T-cell hybridomas were established by hybridization of concanavalin A (Con A)-stimulated human peripheral blood T lymphocytes with cells from a 6-thioguanine-resistant, aminopterin-sensitive mutant line designated CEM-WH4, derived from the continuously growing human T cell line, CEM. High levels of MIF activity were demonstrated in the supernatants of two hybridoma lines, T-CEMA and T-CEMB but not of CEM-WH4 when stimulated with phorbol myristate acetate and phytohemagglutinin. In comparison, MIF derived from Con A-stimulated peripheral blood mononuclear cells showed 100 times less activity. Upon isoelectrofocusing, MIF activity of T-CEMB was found exclusively between pH 4.6 and 5.3 whereas MIF derived from T-CEMA showed heterogeneity with a major peak of MIF recovered at pH 4.6-5.3 and a minor peak at pH 2.4-3.3. These molecules, however, were all found to have an apparent MW of 68,000 and were resistant to trypsin. Most of these characteristics are in accordance with second day pH 3- and pH 5-MIF derived from peripheral blood mononuclear cells. When spleen cells from BALB/c mice immunized with T-CEMB-MIF were used to fuse with NS-1 mouse myeloma cells, nine hybridomas secreting antibodies to human MIF were obtained. Clone D112 which demonstrated the highest MIF-neutralizing activity was found to neutralize MIF derived from T-CEMA, peripheral blood mononuclear cells, and a T cell line, Mo.
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PMID:Generation of human hybridomas producing migration inhibitory factor (MIF) and of murine hybridomas secreting monoclonal antibodies to human MIF. 388 Nov 87

The murine plasma cell alloantigen PC-1 is selectively expressed on B lymphocytes in their terminal phase of differentiation into antibody-secreting cells. Previous work on an analytical scale has shown that PC-1 consists of two apparently identical disulfide-bonded polypeptides, each of Mr 115,000. In this paper, we describe the generation of a monoclonal antibody to PC-1 and its use in the preparative isolation of PC-1 by affinity chromatography. Final purification to apparent homogeneity was achieved by preparative polyacrylamide gel electrophoresis. It was estimated that NS-1 myeloma cells possess 1 to 4 X 10(5) PC-1 monomers per cell on their surface. The yield of PC-1 after purification was approximately 10(5) monomers per cell. Purified PC-1 was digested with trypsin, and the resulting peptides were separated by reversed-phase high-performance liquid chromatography. Purified peptides were sequenced with a gas-phase sequencer.
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PMID:The murine plasma cell antigen PC-1: purification and partial amino acid sequence. 391 81

The immunoglobulin-binding capacity of a Peptococcus magnus strain was studied in a sensitive binding assay using purified human immunoglobulin preparations. The P. magnus strain 312 was capable of binding 48% of polyclonal IgG. Twenty-four of 40 purified myeloma proteins (60%) representing immunoglobulin classes A, G and M showed definite reactivity with an uptake level ranging from 45 to 90%. The remaining 16 monoclonal proteins were non-reactive, binding less than 15%. One myeloma protein with antistaphylolysin and two with antistreptolysin O specificity, i.e. monoclonal proteins with defined antigen specificity, were highly reactive. Binding capacity was observed in all four IgG subclasses and in Ig classes A and M. Twenty-three of 27 myeloma proteins of kappa type were reactive but only one of 13 myeloma proteins of lambda type interacted with the P. magnus strain. Isotope-labelled Fab gamma, F(ab')2 gamma and F(ab')2 alpha fragments were effectively bound by the strain. IgG Fc fragments were completely non-reactive. Isolated light immunoglobulin chains inhibited in a dose-dependent way the uptake of intact IgG to bacteria. Purified heavy chains were non-inhibitory. Isotope-labelled antistaphylolysin IgG F(ab')2 fragments preincubated with staphylolysin were as reactive as free antibody fragments, suggesting that the bacterial binding structure is located outside the antibody-combining site. The immunoglobulin reactivity of P. magnus was not affected by heating the bacteria to 80 degrees C for 5 min nor by treatment with trypsin or sodium metaperiodate. Digestion of 2 X 10(9) organisms with 100 micrograms of pepsin and papain reduced the binding by 58 and 90%, respectively. These data indicate that the binding of immunoglobulin to P. magnus is a non-immune reactivity mediated by a heat-stable surface protein interacting with specific sites on the light chain of the immunoglobulin molecule.
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PMID:A non-immune interaction between the light chain of human immunoglobulin and a surface component of a Peptococcus magnus strain. 393 Sep 51

A monoclonal antibody to human Hageman factor (HF, factor XII) was derived from BALB/c mouse spleen cells fused with NS-1 mouse myeloma cells. This antibody, purified from ascites fluid, reacted with HF to inhibit the activation of HF, purified or in normal pooled plasma, as measured by a coagulation assay. The antibody did not inhibit the coagulant activity of activated HF. The antibody also inhibited the generation of amidolytic activity in HF-ellagic acid mixtures, but failed to inhibit the amidolytic properties of the carboxy-terminal fragment of HF (HFf). Amidolytic activity, absent in an HF-monoclonal antibody mixture, was generated upon treatment with insoluble trypsin. Monoclonal antibody, bound to CNBr Sepharose 4B gel (Pharmacia Fine Chemicals, Piscataway, NJ), reversibly bound HF in plasma or in buffer, without activating it. HF was then eluted with 4 mol/L guanidine HCI. The passage of 125I-labeled HF enzymatically cleaved by trypsin through a column of monoclonal antibody-CNBr Sepharose 4B gel resulted in flow-through of HFf with a molecular weight (mol wt) of 30,000 and HF fragments of mol wt 12,000. Elution with 4 mol/L guanidine HCI yielded several HF fragments (mol wt 80,000, 52,000, and 40,000) but not HFf. These data suggest that the single determinant recognized by the murine monoclonal antibody is not on HFf, but rather on the amino-terminal fragment thought to be involved in the binding activity of HF. The monoclonal anti-HF bound to CNBr-activated Sepharose 4B gel could be used to artificially deplete plasma samples of HF.
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PMID:A monoclonal antibody that inhibits activation of human Hageman factor (factor XII). 396 48

Light polypeptide chains from both normal human gammaG immunoglobulin and Bence-Jones proteins can be cleaved into halves by limited proteolysis with trypsin, pepsin, or papain. The fragments were obtained in yields of up to 22 per cent, had molecular weights of 10,000 to 11,000, and were shown by amino acid analysis and antigenic analysis to correspond to variable or constant regions of light chains. Starch gel electrophoresis in urea suggested that each half consisted of a single polypeptide chain. A fragment from the urine of a myeloma patient corresponded almost exactly to the constant half of a gamma-chain and had a compact shape (Stokes radius of 16 A; frictional ratio of 1.1). Similar Stokes radii were estimated both on fragments from normal urine and fragments produced by proteolysis of normal light chains. The results are consistent with the view that most urinary fragments have a catabolic origin and suggest that there is a small stretch of polypeptide chain between the compact V and C regions of light chains which is particularly susceptible to proteolysis. This lends support to the hypothesis that immunoglobulin chains consist of globular domains connected by more extended stretches of polypeptide chain.
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PMID:Properties of halves of immunoglobulin light chains. 419 96

[(35)S]Cystine-labelled immunoglobulin MOPC21 (IgG1) was prepared from myeloma cells in tissue culture. Carrier myeloma protein was added and the protein was digested with pepsin. The digest was fractionated on Sephadex G-50 into two fractions, further digested with trypsin and again fractionated on Sephadex. Disulphide-bridge peptides were purified by electrophoresis and chromatography and identified by radioautography. A peptide of 96 residues was isolated, which contains both the heavy-light interchain disulphide bridge and all the inter-heavy-chain disulphide bridges. Other peptides were isolated, accounting for all the intrachain disulphide bridges (which could be placed by homology with proteins of other species), except for the variable section of the light chain. Sequences describing this missing disulphide bridge were obtained from totally reduced and alkylated light chains. Peptides related to the interchain disulphide-bridge peptide were isolated from partially reduced and alkylated myeloma protein and from totally reduced heavy chain. The interchain disulphide-bridge peptide was placed at the C-terminal position of the F(ab')(2) fragment, prepared by digestion of the protein with pepsin at pH4.0. Sequences from the heavy-chain intrachain disulphide bridges of MOPC 21 immunoglobulin are compared with homologous sequences from mouse myeloma proteins of other subclasses and proteins of other species.
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PMID:The disulphide bridges of a mouse immunoglobulin G1 protein. 507 37


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