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 human myeloma cell line, PCM6, was newly established from peripheral blood of a patient with advanced IgG myeloma by addition of recombinant interleukin-6 (IL-6) in culture. PCM6 cells had a morphology typical of mature plasma cells. Cytogenetic and surface marker studies confirmed that PCM6 cells were identical to fresh myeloma cells. Coculture of PCM6 cells with normal bone marrow mononuclear cells resulted in increased colony size of bone marrow-derived fibroblastoid colony-forming cells (CFU-F). Conditioned medium of PCM6 (PCM6-CM) cells increased the CFU-F colony size in a dose-dependent manner. The activity was labile to trypsin treatment but was heat stable (60 degrees C, 30 minutes). Molecular weight of the activity was approximately 165 kd by Sephacryl S-300 gel filtration. Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), and IL-1 beta were not detectable in the conditioned medium. These findings suggest that in some myeloma cases, bone marrow stroma may be affected by CFU-F growth-promoting activity.
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PMID:Establishment of a human myeloma cell line with growth-promoting activity for bone marrow-derived fibroblastoid colony-forming cells. 811 25

Three MAb M2, B6, P1 (IgG1 type) against human urinary trypsin inhibitor (UTI), a glycoprotein with antiinflammatory properties, have been produced by hybridization of mouse myeloma cells P3O1 with spleen cells of immunized mice BALB/c. Competitive ELISA-examination of the peroxidase conjugates of M2, B6, and P1 MAb in the presence of the trypsin binding domain shows the M2 antibody to possess the highest affinity for this domain. On the basis of the MAb M2, a competitive ELISA of UTI concentration in urine is proposed. ELISA-detectable changes in the UTI content of urine from patients with nephritis without renal failure can be considered as an early index of renal parenchyma damage.
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PMID:[Monoclonal antibodies to the trypsin-binding domain of trypsin inhibitor from human urine]. 816 56

Three MAb M2, B6, P1 (IgG1 type) against human urinary trypsin inhibitor (UTI), a glycoprotein with antiinflammatory properties, have been produced by hybridization of mouse myeloma cells P3o1 with spleen cells of immunized mice BALB/c. Competitive ELISA-examination of peroxidase conjugates of M2, B6, and P1 MAb in the presence of the trypsin binding domain shows the highest affinity of M2 antibody for this domain. On the basis of MAb M2 competitive ELISA of UTI concentration in urine is proposed. ELISA detectable changes in the UTI content of urine from patients with nephritis without renal failure can be considered as an early index of renal parenchyma damage.
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PMID:Monoclonal antibodies that recognize trypsin binding domain of human urinary trypsin inhibitor. 828 73

The putative matrix metalloproteinase mouse stromelysin-3 was expressed from Escherichia coli and from a mouse myeloma cell line. In the former case a single major protein of 58-kDa was detectable by immunoblotting, but no proteolytic activity could be elicited by zymography or trypsin or organomercurial treatment as would be expected for a typical matrix metalloproteinase. In the latter case immunodetectable proteins of 55-58 and 27-28-kDa were produced. The effect of trypsin or organomercurial treatment of the 55-58-kDa forms was to generate a 51-kDa form and lower molecular mass fragments. Upon zymographic analysis only the 27-28-kDa forms showed caseinolytic activity. N-terminal sequencing and immunoblotting analysis with antibodies specific to distinct domains of stromelysin-3 indicated that the 27-28-Da stromelysin-3 forms had lost the predicted propeptide and the majority of the C-terminal domain. The purified 28-kDa form of stromelysin-3 could weakly degrade a number of extracellular matrix proteins and was inhibited by TIMP. However, the evidence that mature full-length stromelysin-3 is a metalloproteinase could not be substantiated and the precise role of this protein in vivo remains to be elucidated. By partial analogy with interstitial collagenase, one hypothesis is that stromelysin-3 with an intact C-terminal domain has specific properties for an as yet undefined substrate.
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PMID:The 28-kDa N-terminal domain of mouse stromelysin-3 has the general properties of a weak metalloproteinase. 834 Mar 72

Culture supernatants of lipopolysaccharide-stimulated P388D1 macrophage-like tumor cells showed a growth inhibitory effect on plasmacytoma MOPC-315, MPC-11 and myeloma FO cells, but had no effect on J558 plasmacytoma cells. Based on the results of trypan blue staining and a 51Cr release assay, the supernatant had both cytotoxic and cytostatic activity for MOPC-315 plasmacytoma cells. The inhibitory activity was trypsin-sensitive, heat-stable at 100 degrees C for 20 min., but sensitive to 2-mercaptoethanol and cystein HCl. At least 6 hrs of exposure period were required for the P388D1 culture supernatant to show an inhibitory effect on plasmacytoma cells. Since the inhibitory activity could not be blocked by protease inhibitor or neutralized by antibodies to mouse IL-1 beta, IL-6 and TNF-alpha, the inhibitory factor(s) was distinct from the defined cytotoxic factors. After partial purification with DEAE-Sephacel and Sephacryl S-300 chromatography, four major active peaks with the molecular mass of 874-KDa (near the void volume), 112-KDa, 45-KDa and 18-KDa were obtained.
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PMID:Inhibitory effect of lipopolysaccharide-stimulated P388D1 macrophage-like cells on plasmacytoma cells. 835 65

Murine ascites has been shown to contain a variety of growth promoting activities. In this study, we examined the effects of ascites fluid on the efficiency of hybridoma production and cell growth. SP2/0 mouse myeloma cells were injected into peritoneal cavities of mice and ascitic fluid was collected. Lymphocytes from mice immunized with porcine growth hormone (pGH) were fused with myeloma cells in a standard hybridization procedure. These cells were then dispensed in 96-well plates in medium containing either 2.5% ascites or 20% fetal calf serum (FCS) and cultured for few days. Supernatants from these cultures were collected and analyzed for anti-pGH antibodies. It was demonstrated that ascites-supplemented medium increased the efficiency in generating specific antibody-secreting hybridomas by 4-fold over FCS-supplemented medium. Furthermore, hybridoma cells were cultured in microtiter plate and found to proliferate in response to ascites in a dose dependent manner. This effect was abolished by prior digestion of ascites with trypsin, indicating its protein nature. B-lymphocyte related cytokines seemed less likely involved because antibodies to IL-4 and IL-6 failed to alter the stimulatory effect of ascites. Ascites was fractionated by FPLC using Superose 12 column and the active moiety was found to be a small m.w. peptide (< 1,000 dalton). Therefore, murine ascites is capable of substituting for conventional FCS in culture medium in the area of hybridoma technology.
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PMID:Effect of murine ascites on the ability of hybridoma cells to produce antibody and proliferate in vitro. 845 99

Monoclonal free L chains secreted in immunoproliferative disorders are frequently involved in renal complications, including a specific proximal tubule impairment, the Fanconi's syndrome, which is generally featured by intracellular crystallization of L chain-related material. In a patient with myeloma-associated Fanconi's syndrome, hexagonal crystals (most surrounded by smooth membranes) were found in kidney proximal tubular cells and bone marrow plasma cells and phagocytes. The sequence of the patient's monoclonal kappa-chain was deduced from that of identical kappa-cDNA clones from the tumoral plasma cells. Small protein-enriched gel filtration fractions from urine yielded crystals morphologically similar and with the same 60 A periodicity on electron micrographs as those found in the cells. N-terminal sequencing and mass spectrometry studies showed that the crystals contained a 107-amino acid fragment (with a C-terminal lysine) corresponding to the V domain together with a low proportion of the entire kappa-chain. In vitro trypsin and pepsin treatment of the native entire kappa-chain yielded a homogeneous V domain fragment which, contrary to other monoclonal kappa-chains, was completely resistant to further proteolytic attack. The patient's kappa-chain also displayed an unusual self-reactivity, as demonstrated by a Western blot technique. The peculiar proneness of the V domain to resist proteolysis and to form crystals might prevent the normal cell catabolism of the L chain and lead to crystallization and renal impairment.
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PMID:Monoclonal Ig L chain and L chain V domain fragment crystallization in myeloma-associated Fanconi's syndrome. 846 90

We developed a radioimmunoassay (RIA) for the carboxy-terminal telopeptides of type I collagen (ICTP), cross-linked with the helical domain of another type I collagen molecule, after isolation from human femoral bone. The cross-linked peptide was liberated by digesting insoluble, denatured bone collagen either with bacterial collagenase or with trypsin, and purified by two successive reversed-phase separations on HPLC, with monitoring of pyridinoline-specific fluorescence. The purity of the peptide was verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its origin in the type I collagen fibers was determined by amino-terminal amino acid sequencing. Polyclonal antibodies and a separation reagent containing second antibody and polyethylene glycol are used in the RIA. An immunologically identical, somewhat larger antigen is present in human serum; its concentration increases in multiple myeloma and in rheumatoid arthritis. The ICTP antigen seems to be cleared from the circulation by the kidneys, because glomerular filtration rates that are two-thirds of normal or less are associated with increased circulating ICTP concentrations. The CVs of the method are between 3% and 8% for a wide range of concentrations. The analysis of 40 serum samples can be completed in 4 h.
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PMID:Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation. 847 58

An inhibitor of IL-6 binding to the human hepatoma line HepG2 and myeloma cell line U266 was identified in a saline extract of the marine sponge, Callyspongia sp. Functional activity, measured through the increase in haptoglobin production by HepG2 cells stimulated with IL-6, could be strongly inhibited by the extract. Similarly, IL-6-induced production of IgM by the B cell line SKW6.4 was substantially reduced. In neither cell line was there evidence of toxicity produced by the extract. Other sponges of the Callyspongia species were found to contain analogous activity. The activity was destroyed by trypsin treatment or boiling of the extract, suggesting that the inhibition is due to a protein. When the binding of IL-6 to its receptor complex was dissected in vitro, inhibition of binding of IL-6 to soluble receptor by the extract was not detected, but binding of the IL-6-sIL-6R complex to soluble gp130 was inhibited in a dose-dependent fashion. This was borne out in cellular assays since the extract inhibited activation of HepG2 cells stimulated with oncostatin M or leukemia inhibitory factor, cytokines which also use gp130 for signal transduction. These results suggest that the Callyspongia extract contains a protein which blocks the interaction of the IL-6 family of cytokines with their signal transduction moiety, gp130. Elucidation of the structure and mode of action of such a protein would be helpful in designing gp130 antagonists to inhibit the functions of this cytokine family, overproduction of which has been associated with cancer and pathologies of autoimmune disease and AIDS.
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PMID:Characterization of an interleukin 6 cytokine family antagonist protein from a marine sponge, Callyspongia sp. 863 42

Cast nephropathy is a severe complication of multiple myeloma. Binding of filtered monoclonal light chains (LC) with Tamm-Horsfall glycoprotein (THP) triggers heterotypic aggregation of these two proteins to form casts in the distal nephron of the kidney. To localize the LC binding site on THP, human THP was deglycosylated and underwent limited trypsin digestion in the presence or absence of a nephrotoxic LC known to bind THP. A 29.6-kD band was protected from trypsin digestion by the addition of LC. NH2-terminal amino acid sequence and amino acid analyses revealed this band was located between the 6th and 287th amino acid residues of THP. Six peptides located within this 29.6-kD fragment were synthesized and used as potential inhibitors of binding or aggregation of five different nephrotoxic LCs with THP. Peptide AHWSGHCCL (from amino acid 225 to 233) completely inhibited binding and aggregation of these proteins. Optimal inhibition required a cystine residue in this peptide. Truncation experiments demonstrated the entire sequence was necessary for ideal inhibition and the histidine residue explained the effects of pH on binding. These studies provided a basis for further study of LC-THP interaction and a potential approach toward the prevention of cast nephropathy.
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PMID:Localization of a single binding site for immunoglobulin light chains on human Tamm-Horsfall glycoprotein. 904 77


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