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)

Recent studies of the micron- and kappa-chains of the first patient (GLI) with micronHCD indicated that the observed defect was the result of the failure of assembly of the intact kappa-chain to the micron-chain, which lacked the VH domain but had the CH1 Cys normally linked to the light chain. To explore the possibility that the VH region is necessary for the formation of the HL disulfide bond, in vitro studies were performed with GLI micron- and kappa-chains and with the CH1 domain and kappa-chain derived from an IgG3 myeloma protein, KUP, which yields separate VH, CH1, and kappa-chains after papain digestion and reduction. The proteins were reduced and allowed to reoxidize, and the combination products were assessed by gel chromatography under dissociating conditions by SDS-PAGE and by immunoprecipitation techniques. The results suggest that, although in vitro covalent and noncovalent combinations are possible between intact light chains and their autologous heavy chains even in the absence of the VH domain, the efficiency is less than that when the intact Fd region is used. Hence, it seems likely that lack of VH alone is not sufficient to explain the failure of assembly observed in muHCD.
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PMID:The interaction of immunoglobulin heavy and light chains in the absence of the VH domain. 40 2

It was previously shown that digestion of human IgG1/kappa myeloma proteins with pepsin in the presence of 8 M-urea produces fragments which differ from other proteolytic fragments of IgG, including those produced by peptic digestion in aqueous buffers. The two large urea/pepsin fragments each consist of three peptides, and together account for all of the constant region of the light chains and most of the constant region of the heavy chains. Myeloma proteins of subclasses IgG2, IgG3 and IgG4 with kappa light chains were digested with pepsin in 8 M-urea, and the resulting fragments compared with those produced from IgG1/kappa proteins. Gel filtration, starch- and polyacrylamide-gel electrophoresis and sequence analysis have shown that the peptides from each subclass are analogous with those from IgG1. A brief investigation of the products of urea/pepsin digestion of myeloma proteins with lambda light chains has shown that in these proteins light-chain cleavage occurs at residue leucine-182, instead of or as well as at residue 117, where cleavage takes place in kappa chains. Comparison of sequences around sites of urea/pepsin cleavage has shown that pepsin has quite restricted specificity under these conditions.
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PMID:Fragments produced by digestion of human immunoglobulin G subclasses with pepsin in urea. 41 84

Two hybrid cell lines were prepared by the fusion of mouse myeloma cells with the spleen cells of BALB/c mice that had been immunized with the glycolipid ganglio-N-triosylceramide (asialo GM2). The specificity of the monoclonal antibodies produced by these hybridomas, one an IgM and the other an IgG3, has been defined by hemagglutination inhibition, complement fixation, and lysis of glycolipid liposomes by antibody and complement. A major determinant recognized by the IgM antibody is the nonreducing terminal N-acetylgalactosamine including the C6 primary hydroxyl group, but excluding the C2-acetamide group of N-acetylgalactosamine, because oxidation with galactose oxidase produced a structure showing only minimal cross-reaction with the IgM but replacement of the N-acetyl group with an N-n-butyryl group produced a glycolipid that reacts with IgM antibody to the same extent as with the unmodified glycoplipd. A major determinant recognized by the IgG3 antibody is the terminal N-acetylgalactosamine including the C2-acetamido group, but excluding the C6 primary hydroxyl group of N-acetylgalactosamine, because replacement of the N-acetyl group with an N-n-butyryl group produced a glycolipid that did not react with the IgG3 antibody; in striking contrast the IgG3 antibody reacted with the C6-oxidized glycolipid as well as with the native glycolipid. Neither antibody reacted significantly with any other natural glycolipids tested including several that are structurally related to asialo GM2 such as ganglioside GM2, ganglio-N-tetraosylceramide (asialo GM1), or ceramide dihexoside. These results indicated that in addition to the fine structure specificity described above both antibodies recognize the nonreducing terminal GalNAc beta 1 leads to 4Gal structure. The strict antigenic specificity of these monoclonal anti-glycolipid antibodies indicates their great potential as specific probes for cell surface studies.
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PMID:Production of monoclonal antibodies specific for two distinct steric portions of the glycolipid ganglio-N-triosylceramide (asialo GM2). 51 81

The distribution of subclasses IgG1-4 was determined in 84 sera with IgG paraprotein. The results were as follows: IgG1--58.3%, IgG2--25%, IgG3--11.9%, IgG4--4.8%. After division into the group of IgG myelomas (n = 47) and the group of non-myeloma IgG paraproteinemias (n = 37), the following distribution was found: IgG1--55.3%, IgG2--25.5%, IgG3--12.7%, IgG4--6.5% and IgG1--62.1%, IgG2--24.3%, IgG3--10.8%, IgG4--2.7%, respectively. The distribution of light chains in the individual subclasses of IgG paraproteins was also studied. In three double IgG and IgA myeloma paraproteinemias, subclass 1 IgG paraprotein was always demonstrated.
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PMID:Subclasses IgG1--IgG4 in 84 sera with IgG paraprotein. 63 2

Eleven patients are described in whom myelomatosis was complicated by the laboratory and clinical features of the hyperviscosity syndrome (HVS). The myeloma type was IgA in nine and IgG3 in two. In those patients with IgA myeloma the HVS was related to the presence of high molecular weight complexes in the serum. Remission of clinical features was obtained in all patients by plasma exchange. Clinical improvement coincided with reduction of whole blood viscosity and in those patients with IgA myeloma, with a parallel reduction of the high molecular weight complexes. The relationship between the IgA complexes and blood viscosity has been examined by physicochemical analysis of purified IgA monomer and polymers and evidence is presented to show that the IgA polymer has a higher intrinsic viscosity and axial ratio than the larger IgM molecule. The significance of these observations is discussed.
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PMID:Myelomatosis and the hyperviscosity syndrome. 64 50

Examination of 19 S and 7 S anti-alpha(1 leads to 3) dextran (Dex) antibodies by serological assays and isoelectric focusing (IEF) has revealed substantial variation of idiotypic and spectrotypic expression between individuals of the same genotype. 7 S antibodies appeared to be more heterogeneous than 19 S by both methods. A strong, but complex, association was found between the IEF patterns of 19 S and 7 S anti-Dex antibodies and their expression of the idiotypic determinant(s) common to both the M104 and J558 dextran-binding myeloma proteins. However, no such relationship was found between the IEF pattern and the expression of idiotypic determinant(s) unique to the M104 myeloma protein. Rather, indistinguishable spectrotypes from different individuals have widely differing levels of expression of the determinant. In addition, this determinant(s) may be present on different spectrotypes of the same isotype. Both the M104 and J558-specific idiotypes were found on antibodies of the IgG3 subclass as well as in pools containing predominantly the IgG2a subclass. These data confirm and extend the picture of substantial structural variation among the antibodies comprising a response of restricted heterogeneity.
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PMID:Analysis of the diversity of murine antibodies to dextran B1355. III. Idiotypic and spectrotypic correlations. 68 75

The molecular heterogeneity of IgG antibodies to phosphocholine (PC) having a defined idiotype was examined in BALB/c mice immunized with PC-keyhole limpet hemocyanin (KLH). Specific antibodies were separated by isoelectric focusing in polyacrylamide gels and characterized for PC-binding, idiotype, and isotype by direct in situ labeling with 125I-labeled reagents followed by autoradiography. After immunization with PC-KLH, BALB/c produce 20 to 100 microgram/ml of IgM and 80 to 300 microgram/ml of IgG anti-PC antibody. The dominant fraction of anti-PC antibodies in BALB/c (and a lesser fraction in other strains) possesses idiotypic determinants found on a PC-binding myeloma, TEPC-15. Among 65 BALB/c examined, all produced an identical spectrotypic pattern of antibodies possessing T15 idiotypic determinants. Three major sets of T15-idiotype bearing bands were observed, but they belonged to three different IgG subclasses: IgG1, IgG2, and IgG3. These data support the germ line origin for this dominant set of antibodies in the anti-PC repertoire of BALB/c and indicate that they arise from a single rather than multiple VH-VL pairs.
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PMID:Clonal nature of the immune response to phosphocholine. VI. Molecular uniformity of a single idiotype among BALB/c mice. 70 2

Human IgGl, IgG2, IgG3 and IgG4 in WHO pool 67/97, a normal serum pool, Cohn Fraction II and individual sera were examined by crossed immunoelectrophoresis and electroimmunoassay in agarose with IgG subclass specific rabbit antisera. In these methods the fact that IgG subclasses differ in the electrophoretic field is utilized: IgG4 is located anodically, IgG3 cathodically, and IgG2 and IgG1 both anodically and cathodically. The mean, S.D. and range of serum IgG1, IgG2, IgG3 and IgG4 in 20 normal adults found by the electroimmunoassay were given and related to the amount in the WHO pool 67/97. The IgG subclasses values obtained by electroimmunoassay agreed with the values obtained by single radial diffusion. The reproducibility of double determinations (interplate variations) was 1.5--5.5 per cent. Repeated freezing, thawing and storage of the serum at room temperature did not influence quantitation of IgG subclasses. Cohn Fraction II was found to contain smaller amounts of IgG1, IgG2, and IgG4 than those found in the normal serum pools. Crossed immunoelectrophoresis and electroimmunoassay also easily reveal failing quality of IgG subclass antisera. To obtain good antisera in rabbits against IgG subclasses immunization should be done with several myeloma proteins with different electrophoretic mobility within the same subclass.
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PMID:Crossed immunoelectrophoresis and electroimmunoassay of human IgG subclasses. 71 25

Groups of BALB/c mice were treated with various conjugates of 2,4 dinitrophenyl (DNP) and BALB/c myeloma proteins belonging to the four subclasses of IgG (IgG1, IgG2, IgG2b, IgG3). Immediately therafter, they were challenged with DNP-keyhole limpet hemocyanin in complete Freund's adjuvant and antibody to the hapten was measured by direct and indirect hemolytic plaque assay. The results show that all subclasses of IgG are effective as tolerance-inducing carriers. However, the ability of induce tolerance is dependent upon the concentration of hapten bound to each myeloma protein. Tolerogenic conjugates suppress both direct and indirect plaque-forming cells in all types of antibodies measured (IgG1, IgG2a, IgG2b, IgGa), whereas, non-tolerogenic conjugate failed to suppress them. The intact molecule of IgG but not its fragments (Fab, F(ab)2', Fc) appear necessary as tolerance-inducing carriers. It is suggested that the ability to induce tolerance is related to the capacity of the tolerogenic conjugates to cause receptor blockade.
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PMID:Carrier determined tolerance with various subclasses of murine myeloma IgG. 76 77

Fluorescein-conjugated heat-aggregated human IgG binds to endothelial cells of foetal stem vessels in cryostat sections of normal, full-term human placentae. No binding was observed using native human IgG of heat-aggregated human albumin, IgM or IgA2. No inhibition of binding of heat-aggregated human IgG was observed by pre-treatment of placental tissue sections with native IgG or non-aggregated Fc fragments. The binding was blocked using heat-aggregated Fc fragments prepared from IgG1, IgG2, IgG3 and IgG4 myeloma proteins, but not with heat-aggregated human light chains, Fab and F(ab)2 fragments of human IgG, or with heat-aggregated human IgM and IgA2. It is suggested that the placental endothelial cell receptor for aggregated IgG may function to keep immune complexes from entering the foetal circulation.
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PMID:Immunological studies of human placentae: subclass and fragment specificity of binding of aggregated IgG by placental endothelial cells. 78 32


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