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)

The detection of Bence Jones protein, an important part of the investigation of suspected myeloma, is most commonly done by agarose or cellulose nitrate electrophoresis followed by immunofixation. Bence Jones protein is recognized as single or multiple bands of one type of light chain. Unfortunately, improvements in sensitivity of these techniques (use of high-affinity antisera and higher resolution electrophoresis) frequently allow detection of multiple light chain bands in the urine of patients who do not have a B-cell dyscrasia. The bands are usually kappa, although they may be accompanied by lambda bands. This pattern may lead to the misdiagnosis of Bence Jones protein and oligoclonal light chain production in patients. Here we show that this pattern is produced by polyclonal light chains; it is present in the urine of all patients with a tubular proteinuria of any etiology and may be induced in healthy individuals by blocking their renal tubular protein reabsorption. Polyclonal light chains separate into monomers and dimers on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and into four major bands with many minor bands by isoelectric focusing. This difference in charge and possibly size results in the banding pattern seen on good-quality electrophoresis and immunofixation.
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PMID:Restricted electrophoretic heterogeneity of immunoglobulin light chains in urine: a cause for confusion with Bence Jones protein. 190 42

Murine hybridoma-derived monoclonal antibody (MCA) to Dunning rat prostate adenocarcinoma R-3327HIS (androgen independent type) has been produced by fusing P3x63 Ag8-653 myeloma cells with splenocytes of BALB/c mice which were immunized with R-3327HIS tumor cell membranes. One monoclonal antibody designated MCA-R1 (IgG2a subtype) produced an intense immunostaining of various androgen independent Dunning rat prostate tumor sublines (HIS, HIM, HIF, AT-1, AT-2, AT-3, MAT-Lu and MAY-Ly-Lu), but did not stain other tumors of rat origin or normal rat tissues. Marginal immunostaining was detected in the androgen responsive R-3327H and R-3327G tumor subline. Although MCA-R1 antibody did not react with the regressed prostate tumor of R-3327H or R-3327G, it strongly reacted with the relapsed prostate tumor from either R-3327H or R-3327G tumor derived from rats were treated with diethyl stilbestrol (DES) or castration. MCA-R1 antibody also produced a strong cross-reaction with human prostate adenocarcinoma. Like the Dunning rat tumor, human adenocarcinoma exhibited distinct immunostaining patterns with respect to intracellular localization among well differentiated, moderately differentiated and poorly differentiated tumor. Benign prostatic hyperplasia or other normal tissues did not stain. Immunofluorescence, immunoprecipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and radioautographic analysis revealed that the Dunning rat prostate tumor antigen recognized (m.wt. 50 and 120 Kd) by MCA-R1 antibody are localized on both cell surface and in the cytoplasm. This MCA may represent a potential reagent for the study of tumor biology and immunotherapy of prostate tumor.
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PMID:Murine monoclonal antibodies reactive with a variety of androgen independent Dunning rat prostate adenocarcinoma sublines also reactive with human prostate adenocarcinoma. 205 91

Human prothymosin alpha, virtually alone among proteins, is recovered from the aqueous phase of phenol-extracted cell lysates prepared from human myeloma cells or COS cells that were transfected with the human prothymosin alpha gene. This observation forms the basis for purification of the protein to homogeneity in two steps--phenol extraction followed by electrophoresis in sodium dodecyl sulfate polyacrylamide gels to remove residual contaminants consisting chiefly of carbohydrate and RNA.
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PMID:Human prothymosin alpha: purification of a highly acidic nuclear protein by means of a phenol extraction. 213 39

Monoclonal antibodies to performic acid-oxidized cellular retinoic acid-binding protein (CRABP) from bovine retina were prepared by fusion of spleen cells from immunized mice with mouse myeloma cells. Five antibodies were studied in detail. It was established by ELISA that the antibodies react with CRABP and oxidized CRABP, but not with other oxidized or unmodified retinoid-binding proteins. Competitive ELISA demonstrated that the antibodies react with heat-denatured antigen but not with native protein. Western blotting and immunostaining, following sodium dodecyl sulfate gel electrophoresis, provided evidence for recognition of a single component in retinal supernatants whose staining is prevented by preabsorption of the antibody with heat-denatured CRABP. The insoluble fraction from a retinal homogenate contains residual CRABP and two weakly-reacting components, whose staining is not affected by preabsorption of the antibody with antigen. Each antibody produces the same staining pattern on cryostat sections of rat retina by indirect immunofluorescence. Amacrine somata on both sides of the inner plexiform layer are labeled, as well as processes forming laminae within this layer. These results suggest that retinoic acid may play a functional role in the inner retina.
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PMID:Localization of cellular retinoic acid-binding protein to amacrine cells of rat retina. 216 45

Human anti-cytomegalovirus (CMV) monoclonal antibody designated C23 was purified from the culture fluid of hybridoma cells which were generated by cell fusion of human lymphocytes and mouse myeloma cells. The purified C23 was found to be identical to human gammaglobulin (HGG) in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under both reducing and non-reducing conditions and in gel filtration chromatography. C23 was not contaminated with either aggregated IgG molecules or mouse immunoglobulin chains. In addition, the formulated C23 preparation showed an anti-complement activity low enough to permit its use as a biologic. A virus neutralization titer of C23 was about 1,000 times higher than the titers of HGG preparations. All the tested CMV strains were susceptible to neutralization by C23 and this neutralization was not affected by addition of either beta 2 microglobulin or fresh human serum. These results suggest that human monoclonal antibody C23 is as safe as conventional HGG preparations which have been used in humans, and much more effective in providing host protection against CMV infection.
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PMID:Characterization of human anti-cytomegalovirus monoclonal antibody as biologics. 216 40

The whole-cell configuration of the patch-clamp technique was used to study the outward Na+ current through Ca channels in hybridoma cell lines (202B and 206), constructed by fusion of S194 myeloma cells with murine splenic B lymphocytes. The concentration of Na+ in the electrode solution, [Na+]p, was changed by isosmotic replacement of Na+ with N-methyl-D-glucamine+ ions. When 2.5 mM calcium was present in the bath, neither the current nor the reversal potential was significantly altered by changes in the level of external Na+ [( Na+]o. By contrast, both of those properties were strongly affected by [Na+]p. At fixed depolarizing potentials, the outward current increased approximately as the square power of [Na+]p, a feature that cannot be easily explained by one-ion models for a channel or by "continuum" theories based on electrodiffusion. Instead, all the data could be well described by a "single-file" model for a two-site pore that admits up to two ions. Although double occupancy of the Ca channel by divalent cations has been proposed previously (Hess and Tsien. 1984. Nature. 309: 453-456; Almers et al., 1984. J. Physiol. 353: 585-608), this study indicates that, in our system, states of the channel with two Na+ ions must also be considered in order to explain the dependence of the outward current on [Na+]p. A good fit to the data could be obtained by assuming that both sites in the channel are "electrically" close to its cytoplasmic end and that most of the voltage dependence pertains to the rates for ion exit to the external medium. The values of the parameters suggest that: (a) Ca2+ is bound most strongly by the site nearest to the cytoplasm (in both singly and doubly occupied channels); (b) in channels with two Ca2+ ions, the dissociation constant of the site close to the external mouth must be greater than 2.5 mM; and (c) in pores occupied by two Na+ ions, the rate constant for Na+ exit to the external solution is larger than the rate constant for Na+ exit to the cytoplasm.
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PMID:Effects of internal Na+ on the Ca channel outward current in mouse neoplastic B lymphocytes. 217 42

We have synthesized three peptides with amino acid sequences corresponding to amino acids 533-547, 597-611, and 765-779 of the human progesterone receptor (hPR). These peptides were conjugated to keyhole limpet hemocyanin and injected into mice and rabbits to develop antibodies to hPR. Antibodies to the undenatured form of PR were elicited only by the peptide with amino acid sequence 533-547. Fusion of SP2/0 myeloma cells with spleen cells from mice immunized with this peptide produced several active clones. Rabbit sera from immunized animals produced one antiserum that reacted with the undenatured form of PR. One monoclonal antibody (PR-AT 4.14) and one antiserum (PR-AT533) raised against peptide-(533-547) were characterized. Binding of these antibodies to the undenatured form of PR was demonstrated by analysis of the antibody-receptor complexes on sucrose density gradients and by immunoprecipitation techniques. Binding of PR to the antibodies was inhibited by excess peptide. The antibodies did not react with estrogen, glucocorticoid, or androgen receptors, but recognized PR from human breast cancer as well as calf, rabbit, mouse, and rat uteri, indicating that this epitope was conserved among these species. Based on sucrose density gradient analysis of PR prepared and labeled in the presence of proteolysis inhibitors and sodium molybdate, the antibodies bound to a site on the intact undenatured PR, but failed to bind to partially degraded steroid-binding form of the receptor, suggesting that the antibody-binding domain is at or near a site sensitive to proteolysis.
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PMID:Monoclonal and polyclonal antibodies to human progesterone receptor peptide-(533-547) recognize a specific site in unactivated (8S) and activated (4S) progesterone receptor and distinguish between intact and proteolyzed receptors. 220 32

Spleen cells from inbred Biozzi mice, immunized against the human breast cancer cell line T47D, were fused with murine myeloma SP2O cells to generate monoclonal antibodies. One of these, 1BE12, of IgM isotype, reacted with five of six human breast tumor cell lines, while no binding was detectable with normal lymphocytes, RBC, or fibroblasts. The antigen recognized by monoclonal antibody 1BE12 was localized on the surface of T47D and MCF7 cells and was detected in cell-free supernatants of cultures. The antigen was found also on the surface of milk secretory cells. Immunohistochemical staining of frozen and paraffin-embedded sections of human tissues showed apical polarized reactivity in normal breast glands, while in all breast cancers staining was either cytoplasmic or membranous and heterogeneously distributed. Immunostaining was also observed in some other normal epithelia, including salivary gland, gastroduodenal mucosa, exocrine pancreas, and cervix. The antigen was not detectable in secretory endometrium, whereas proliferative endometrium was strongly stained. Colon carcinoma, and cancers of the bladder and endometrium were strongly reactive. No staining was detected in melanoma, lymphoma, mesothelioma, non-small cell lung carcinoma, and thyroid, renal, and ovarian carcinomas. Lectin absorption of MCF7 membrane extracts reduced 1BE12 binding. A large reduction in 1BE12 reactivity was observed after digestion of T47D and MCF7 membrane extracts with proteases. Treatment with sodium periodate resulted in complete loss of antigenicity, while neuraminidase treatment did not affect 1BE12 binding. These findings suggest that the 1BE12 epitope is expressed on the carbohydrate moiety of a glycoprotein and does not contain sialic acid. Immunoblotting of the perchloric acid-soluble fraction of MCF7 membrane extracts after electrophoresis in 1% agarose detected the antigen as a high molecular weight species (Mr greater than 900,000). The antigen was purified by perchloric acid extraction of MCF7 membrane preparations followed by affinity chromatography on 1BE12 antibody coupled to Sepharose-4B and gel exclusion fast protein liquid chromatography. No reactivity of the purified material was found with monoclonal antibodies directed against human milk fat globule membrane-associated mucins HMFG1 and DF3.
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PMID:Characterization and distribution in human tissues of a glycoproteic antigen defined by monoclonal antibody 1BE12 raised against the human breast cancer cell line T47D. 222 61

Autologous (Heymann) nephritis was induced by immunizing Sprague-Dawley rats with a crude membrane extract (Fx1A) prepared from renal cortical tubules. Urine protein excretion was monitored to determine the onset of nephritis and then the spleens of nephritic rats were fused with a non-secretor rat myeloma cell line. Supernatants from hybridoma cultures were first screened for production of anti-brush border membrane (BBM) antibody by immunodot blotting of highly purified rat BBM on nitrocellulose. Positive hybrids were then tested by indirect immunofluorescence for the presence of IgG, which binds to the brush border of rat renal proximal tubules. Those hybrids which were positive by both screening assays were subcloned twice. Two monoclonal antibodies (C5, D11) were studied in some detail. Both C5 and D11 immunoprecipitated a single polypeptide from BBM, labelled with 125I by the lactoperoxidase method. Radioautography of gradient 4-11% slab sodium dodecyl sulphate polyacrylamide gels revealed that the polypeptide against which C5 and D11 were directed co-migrated with the polypeptide immunoprecipitated by (i) IgG eluted from the renal cortex of nephritic rats, and by (ii) a mouse anti-rat monoclonal against gp 330 [a BBM constituent with proven pathogenicity [9]]. Supernatants which tested positive by immunodot blotting but negative by indirect immunofluorescence showed no detectable immunoprecipitate after reaction with BBM. Immunocytochemical staining by immunoperoxidase and immunogold methods localized C5 and D11 to the BBM of the renal proximal tubule and to the urine face of the glomerular epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A rat hybridoma model of Heymann nephritis: production of a monoclonal anti GP330 from a nephritic rat. 227 21

Tubulointerstitial nephritis (TIN) was induced by monoclonal anti-tubular basement membrane (TBM) antibodies. Hybridomas producing anti-TBM antibodies were produced by the fusion of a mouse parental cell line with BALB/c mice which had been immunized with Wistar rat renal cortices. Three hybridoma cell lines were selected for production of antibodies against proximal TBM by indirect immunofluorescence. The isotypes of these monoclonal antibodies (MoAbs) were determined to be of the IgM class by double immunodiffusion. Subsequently, 6-week-old female BALB/c mice were injected intraperitoneally with cells (1 x 10(7)) of anti-TBM antibody-producing hybridomas, 39-1, 39-4, or 339-3. As a control, a monoclonal IgM-producing myeloma cell line was used. Proteinuria developed from Day 8, reaching 200 to 300 mg% in mice from the experimental groups, while in the control mice, urinary protein did not exceed 50 mg%. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, the excreted urinary proteins proved to be of low molecular weight. An immunofluorescent study revealed a linear localization of IgM along the proximal TBM from Day 4, and light microscopy showed focal degenerative alteration in proximal tubules and focal round cell infiltration in the interstitium. Electron microscopy revealed dense deposits on some proximal TBM. These results indicate that monoclonal anti-TBM IgM antibodies can induce TIN as a result of persistent production of antibodies from intraperitoneally injected hybridomas.
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PMID:Tubulointerstitial nephritis induced by monoclonal anti-proximal tubular basement membrane antibodies in mice. 229 6


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