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)

A monoclonal IgG1 lambda protein with peculiar cryoprecipitable characteristics was found in the serum of a patient with advanced multiple myeloma. The cryoprecipitate was observed only when the serum was exposed to the air. Further studies defined this phenomenon as being strictly pH-dependent. No antiglobulin activity (rheumatoid factor) was detected in the cryoglobulin. The isoelctric focussing of isolated cryoglobulin showed four distinct fractions around the pH 7.8 zone, which was comparable to the pH at which the cryoprecipitate began to form. Electrostatic bonds probably contribute to the mechanism involved in the formation of cryoprecipitate in this case.
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PMID:Monoclonal IgG1 immunoglobulinaemia with strictly pH dependent cryoprecipitability. 4 Jul 21

Ten IgM polyclonal rheumatoid factor (RF) preparations isolated from sera from various patients with rheumatoid arthritis (RA) were investigated with respect to their variable heavy chain (VH) subgroups. They were tested in a haemagglutination inhibition system using red cells sensitized with myeloma proteins with known chemical VH subgroups and anti-VH subgroup specific antisera. Most of the preparations showed a considerable degree of restriction to one VH subgroup. Seven of the IgM-RF preparations were restricted to the VHIII subgroup, two to the VHI subgroup and one to the VHII subgroup. However, a weak reaction in other VH subgroup systems was seen in several instances. Two normal IgM fractions from healthy persons showed no VH subgroup restriction, and showed a rather similar degree of reaction in all the three subgroup systems.
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PMID:A study of the variable heavy chain (VH) regions in human polyclonal IgM rheumatoid factors. 40 21

The Sia test was performed in strictly standardized conditions in boiled, bidistilled, deionized water (BBD) and in 0.01 M phosphate buffers pH 5.0 and 7.0. Normal human sera and sera from patients with diffuse hypergammaglobulinemia ( greater than 2.0 g/100 ml), immunoglobulin G (IgG) myeloma (M component greater than 5.0 g/100 ml), and Waldenstrom's macroglobulinemia were studied. In BBD all normal sera were Sia-negative, whereas 16 per cent of sera with diffuse hypergammaglobulinemia, 60 per cent of sera with IgG M component, and 44 per cent of macroglobulinemic sera with Sia-positive. Almost all sera from the above mentioned four groups gave positive results in phosphate buffer pH 5.0 and the majority of them, with the exception of normal human sera, gave positive results at pH 7.0. All precipitates isolated from the sera tested showed beta-alpha 2 bands in cellulose acetate electropherograms. Precipitates from the sera with diffuse hypergammaglobulinemia also showed gamma bands, and those from the myelomatous or macroglobulinemic sera showed strong bands corresponding to the M components. Whereas immunoelectrophoresis of the four-fold-concentrated precipitates showed up to 11 precipitation lines, radial immunodiffusion detected up to 18 proteins. The characteristic pattern of IgM/IgG immune complexes was observed in immunoelectrophoresis of Sia precipitates from hypergammaglobulinemic sera with rheumatoid factor. The recovery of immunoglobulins in the Sia precipitates varied greatly but that of IgM was usually greater than that of IgG or IgA. It may be concluded that the Sia test is entirely nonspecific regardless of the buffer or pH at which it is performed. The only advantages of this test seem to be the quick partial purification of IgM components and identification of their light chains, and the possible detection of immune complexes.
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PMID:Immunochemical and physical studies of the Sia test. 81 99

In this survey for rheumatoid factor (RF) seropositivity on patients with neoplasms, an 85% rate of positive screening tests was recorded under certain circumstances. This high rate of RF seropositivity occurred after irradiation and/or chemotherapy of breast and lung cancers. Treated patients with breast cancers who had no evidence of residual tumor had an 89% rate of positive RF tests. Conversely, the incidence of RF seropositivity was low among untreated patients with similar tumors and treated patients with glioblastomas or multiple myeloma. The administration of cytotoxic drugs (e.g., azathiprene) was not itself associated with RF production even in renal allograft recipients. The data indicate that RF production occurs frequently after therapy of certain tumors and suggest that in these circumstances RF may be an expression of tumor-host interaction.
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PMID:Rheumatoid factor and tumor-host interaction. 106 77

The authors confirm the great rarity of joint complications in patients with Kahler's disease. Among the records of 1953 cases the following complications were the only one found: 2 cases of proved articular amylosis, 2 cases of probable articular amylosis, 3 cases of possible articular amylosis, 20 cases of arthropathy that were impossible to classify, 27 cases of compression of the median nerve in the carpan canal, 6 cases of gouty arthritis, and 3 cases of septic arthritis. The data on symptoms obtained in the course of this enquiry are in conformity with the data in the literature. Articular amylosis often takes on the appearance of a polyarthritic syndrome of progressive installation and extension, involving in particular the hands and the wrists, but sometimes involving in a symmetrical bilateral manner the elbows, the shoulders, and the knees. The affected joints are swollen, stiff, and painful. Local signs of inflammation are, however, often absent. The deformations characteristic of rheumatoid arthritis do not develop. The joints do not show radiological signs for most of the time. In addition, it is not possible to detect the rheumatoid factor in the serum. The arthropathies can also assume an oligo-articular topography. Articular discharges are very frequent: they are usually of a mechanical nature. Whatever the clinical appearance, an exact diagnosis can be established only by means of anatomo-pathological examination of the synovial membrane or of certain para-articular amyloid nodules. Myelomas complicated by amyloid articular deposits are often light chain, with only little increase in the erythrocyte sedimentation rate, discrete hyperproteinaemia, moderate medullary plasmocytosis, and rare or limited radiological lesions. The carpal canal syndrome is either isolated or included within the framework of a polyarthropathy. Compression of the median nerve is due to amyloid infiltration into the synovial sheath of the tendons of the finger flexors, proof of which is not always easy. Gout is rare despite the frequency of hyperuricacidaemia caused by renal insufficiency. Septic arthritis is often caused by renal insufficiency. Septic arthritis is often caused by pneumococci to which those with a myeloma appear particularly suceptible.
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PMID:[Articular complications of Kahler's disease. Results of a survey of 1953 cases of plasmocytic myelomas]. 112 74

Immunological data are reported from 19 cases of immune-mediated disease recorded in the old English sheepdog breed in Western Australia between 1978 and 1989. The conditions included autoimmune haemolytic anaemia (seven), idiopathic thrombocytopenia (one), Evans' syndrome (five), multiple myeloma (two), systemic lupus erythematosus (one), discoid lupus erythematosus (one) and hypothyroidism (two). The most consistent serological findings were raised serum IgG (60 per cent), depressed serum IgM (60 per cent) and the presence of multiple autoantibodies (anti-red blood cell 78 per cent, antinuclear antibody 44 per cent, rheumatoid factor 19 per cent). An underlying, breed-related disorder of immune regulation may account for these observations.
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PMID:Immune-mediated disease in the old English sheepdog. 141 Aug 24

We report the clinical data and results of biochemical studies of amyloid in a postpartum patient. The amyloidosis was not associated with myeloma, and immunopathologic examination of the amyloid deposits gave inconclusive results. Biochemical analysis of the deposits proved that the amyloid protein JUN was derived from the variable region of the kappa light chain subgroup III and is homologous to a rarely expressed protein POM, which was previously shown to have rheumatoid factor activity. The significance of this association and the diagnostic problems associated with certain cases of amyloid derived from immunoglobulin light chain (type AL) are discussed.
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PMID:Biochemical characterization of amyloid derived from the variable region of the kappa light chain subgroup III. 211 14

MRL-lpr/lpr mice spontaneously develop a lupus-like syndrome characterized by immunopathological manifestations such as necrotizing vascular lesions of ear tips and severe glomerulonephritis. Similar skin vascular and glomerular lesions associated with cryoglobulinemia can be induced in normal mice by injection of a monoclonal antibody (mAb)--6-19 (gamma 3 heavy chain and kappa light chain), exhibiting both cryoglobulin and anti-IgG2a rheumatoid factor (RF) activities--derived from the MRL-lpr/lpr autoimmune mouse. To determine the role of RF and/or IgG3 Fc fragment-associated cryoglobulin activities in 6-19 mAb-induced tissue lesions, a 6-19-J558L hybrid mAb (gamma 3 heavy chain and lambda 1 light chain) was produced by fusion between the 6-19 hybridoma and the J558L myeloma. Here we report that the 6-19-J558L hybrid mAb, which loses the RF activity but retains the cryoglobulin activity, fails to induce skin vascular lesions. However, it is still able to provoke glomerular lesions identical to those caused by the 6-19 mAb. Further, we have observed that the depletion of the corresponding autoantigen, IgG2a, in mice by treatment with anti-IgM antisera from birth also prevents the development of skin but not glomerular lesions. Our results indicate that both RF and cryoglobulin activities of the 6-19 mAb are required for the development of skin vasculitis, but its cryoglobulin activity alone is sufficient to cause glomerular lesions. In addition, cDNA cloning and sequencing of the 6-19 mAb has revealed that the 6-19 kappa light chain variable region amino acid sequence is encoded in a germ-line configuration, suggesting that immunoglobulin variable region germ-line genes could contribute to the generation of pathogenic autoantibodies.
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PMID:Cryoglobulinemia induced by a murine IgG3 rheumatoid factor: skin vasculitis and glomerulonephritis arise from distinct pathogenic mechanisms. 226 5

To assess the specificity of anti-nuclear antibodies with cross-reactive rheumatoid factor (RF) activity, monoclonal anti-DNA and anti-Sm antibodies from MRL-lpr/lpr mice were tested for binding to a variety of IgG antigens. These antibodies had all been previously identified as binding heterologous IgG. By ELISA, antibodies in this panel all bound BALB/c myeloma proteins representing the different IgG subclasses, indicating broad reactivity with murine IgG as well as heterologous IgG. The determinant recognized by these antibodies was further investigated using the Fab, F(ab')2 and Fc fragments of both human as well as rabbit origin. All antibodies bound well to fragments as well as intact IgG antigens. These antibodies were further analysed by Western blotting, demonstrating that most bound to both heavy and light chains of human origin. Together, these observations suggest that some anti-nuclear antibodies bind a conserved antigenic determinant present widely on immunoglobulin chains. This determinant may represent a common sequence important in immunoglobulin domain structure.
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PMID:IgG binding of monoclonal anti-nuclear antibodies from MRL-lpr/lpr mice. 227 42

Two monoclonal IgM natural autoantibodies (E7 and D23) obtained from the fusion of normal, nonimmunized, BALB/c mouse spleen cells and nonsecreting myeloma cells were selected on the basis of their polyreactivity with auto- and xenoantigens and chemical haptens. Nucleotide sequence analysis of the variable and constant regions of the heavy and light chains showed the following. (i) The antibodies arise from different genetic elements with very low or no homology--E7 from a heavy-chain variable region (VH) of family 36-60 and kappa light-chain variable region (V kappa) from a group 19--whereas D23 derives from a VH of family Q52 and V kappa derives from group 8. (ii) E7 and D23 are probably of germ-line origin, as suggested by high homology with VH genes from the unrearranged genome. Compared with the germ-line VH 1210.7 gene, E7 has a single nucleotide difference leading to a silent mutation at position 15, whereas D23 seems to be encoded by germ-line VH 101 with one nucleotide difference causing replacement of Ser-84 by Ala. (iii) The genetic V kappa and VH elements for E7 and D23 also give rise to different responses to phenyloxazolone, dinitrophenyl, 5-(dimethylamino)naphthalene-1-sulfonyl, arsonate, phosphocholine, and influenza virus hemagglutinin. Antibodies from normal and autoimmune mice with rheumatoid factor-like activity are also homologous to E7 and D23. These results indicate that polyreactive autoantibodies are encoded by germ-line genes and that, starting with the preimmune poly- and autoreactive repertoire, mutated forms of antibodies recognizing exogenous antigens can be obtained and selected.
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PMID:Two murine natural polyreactive autoantibodies are encoded by nonmutated germ-line genes. 249 87


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