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 58-kDa Golgi protein (gp58) was previously identified and found to be concentrated in cis Golgi cisternae in several cell types (Saraste, J., Palade, G.E., and Farquhar, M.G. (1987) J. Cell Biol. 105, 2021-2029). In this study the protein was partially purified from rat pancreas and mouse myeloma cells in order to characterize its oligosaccharides. It migrated on sodium dodecyl sulfate-polyacrylamide gels as a 57-58-kDa doublet under reducing conditions or as a single approximately 116-kDa band under nonreducing conditions. Pancreatic gp58 was susceptible to alpha-N-acetylgalactosaminidase digestion and it bound concanavalin A, Helix pomatia, Dolichos biflorus, soybean agglutinin, and Bauhinia purpurea lectins, but not Ricinus communis agglutinin or lectins from Griffonia simplicifolia-1, Arachis hypogaea, and Limulus polyphemus. It bound Ricinus communis agglutinin after galactosylation with GlcNAc galactosyltransferase. These data demonstrate that pancreatic p58 contains immature N-linked moieties with nonreducing terminal GlcNAc residues as well as the initiating GalNAc of O-linked glycoproteins. Myeloma gp58 was sensitive to endo-beta-N-acetylglucosaminidase H, and oligosaccharide analysis of its [3H]glucosamine-labeled glycopeptides indicated that it also contained immature N-linked glycans. Some of the latter consist of high mannose chains (high affinity for concanavalin A, endo-beta-N-acetylglucosaminidase H-sensitive), but the predominant (95%) species are neutral tri- or tetraantennary N-linked chains containing GlcNAc (no binding to concanavalin A). Glycopeptides from biosynthetically labeled myeloma cells did not contain detectable base labile oligosaccharides, indicating that unlike pancreatic p58, myeloma gp58 may not be an O-linked glycoprotein. Neither pancreatic nor myeloma gp58 contained terminally processed oligosaccharides, indicating that gp58 has not been modified by trans-Golgi glycosyltransferases. Thus, the oligosaccharide content of gp58 is consistent with the assumption that this protein is retained in the cis Golgi cisternae during biosynthesis instead of being transported across the Golgi stacks and targeted back to the cis Golgi from the trans side.
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PMID:A 58-kDa resident protein of the cis Golgi cisterna is not terminally glycosylated. 189 39

Two murine monoclonal antibodies (MAbs) against Aspergillus fumigatus were produced and characterized. Splenocytes from cell wall-immunized BALB/c mice were fused with SP2/0 myeloma cells. The hybridomas were screened with a cold alkali (CA) extract of mycelium containing protein, mannose, and galactose, and two MAbs of the immunoglobulin M class were purified from ascites fluid. MAbs 1 and 40 were characterized by double immunodiffusion against CA antigen, indirect enzyme immunoassay with mannans of Candida albicans serotypes A or B or Candida tropicalis, indirect immunofluorescence with C. albicans- or A. fumigatus-infected tissues, indirect immunofluorescence with smears of other pathogenic fungi, Western blotting (immunoblotting) with the lectin concanavalin A or BS-1 from the seeds of Bandeirea simplicifolia, and immunoelectron microscopy. MAb 1 did not cross-react with Candida mannan and recognized a periodate-sensitive, pronase- and heat-resistant epitope in CA antigen and three mannose- and galactose-containing components (80, 62, and 49 kilodaltons) of a mycelial homogenate. Immunoelectron microscopy demonstrated binding of MAb 1 to the inner cell wall and intracellular membranes of hyphae and conidia of A. fumigatus. Circulating antigen was detected in experimental invasive aspergillosis by inhibition enzyme immunoassay with MAb 1 and CA antigen. MAb 40 was a nonprecipitating antibody cross-reactive with Candida species, and competition for an epitope located diffusely in the cell wall of A. fumigatus hyphae was demonstrated by incubating MAb 40 with mannan of C. albicans serotype A. These results suggest that MAb 1 recognizes immunodominant oligogalactoside side chains of A. fumigatus galactomannan, while MAb 40 binds to mannopyranosyl side chains common to A. fumigatus galactomannan and C. albicans mannan.
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PMID:Production and characterization of monoclonal antibodies to cell wall antigens of Aspergillus fumigatus. 219 59

A monoclonal antibody against rat neutrophils, RP-1, was produced by hybridizing a mouse myeloma (P3-X63-Ag8.653) with BALB/c mouse spleen cells sensitized with peritoneal neutrophils from Wistar-King-Aptakeman/Hok rats. RP-1 specifically reacted to neutrophils and bone marrow cells from rats of various strains. The expression of an antigen reactive to RP-1 on rat peritoneal neutrophils was enhanced by stimulation with phorbol myristate acetate and concanavalin A. The experimental result that the expression of an antigen reactive with another anti-neutrophil monoclonal antibody was not enhanced by stimulation with phorbol myristate acetate indicates that the antibody-binding capacity of stimulated neutrophils was not nonspecifically enhanced. The enhancement of antigen expression was temperature dependent. A glycolytic inhibitor, 2-deoxy-D-glucose, and an inhibitor of intracellular calcium mobilization, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl ester hydrochloride, which inhibited hydrogen peroxide release from stimulated neutrophils, did not inhibit enhancement of the expression of an antigen reactive with RP-1.
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PMID:Enhancement of the expression of a rat neutrophil-specific cell surface antigen by activation with phorbol myristate acetate and concanavalin A. 242 75

A panel of lectins was used to study surface carbohydrate expression on myeloma cells with the aim of finding a possible agent for in vitro bone marrow purging. Peanut agglutinin (PNA, galactose beta 1,3 N-acetylgalactosamine-binding) bound to all plasma cells in 33/34 bone marrow samples from myeloma patients and to all plasma cells in 11 bone marrow from patients with monoclonal gammopathy of undetermined significance and 10 normal bone marrow samples. Bone marrow and peripheral blood monocytes reacted weakly with PNA except in one case of acute monoblastic leukaemia and two of chronic myelomonocytic leukaemia in which monocytes were strongly positive. The only case of plasma cell leukaemia studied was PNA negative. All other bone marrow mononuclear cells were negative for PNA but became positive after sialidase treatment. Peanut agglutinin may have potential as an agent to be used in myeloma for in vitro marrow purging prior to autologous transplantation in combination with high dose chemotherapy.
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PMID:Peanut agglutinin shows specificity for bone marrow plasma cells. 246 73

Asparagine-linked sugar chains were quantitatively released as oligosaccharides from human IgG2 and IgG4 myeloma proteins by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. Each oligosaccharide was isolated by serial lectin column chromatography. Study of their structures by sequential exoglycosidase digestion and methylation analysis, revealed that all of them were of the bi-antennary complex-type containing Man alpha 1-6(+/- GlcNAc beta 1-4)(Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(+/- Fuc alpha 1-6)GlcNAc as core structures, and GlcNAc beta 1-, Gal beta 1-4GlcNAc beta 1- and Sia alpha 2-6Gal beta 1- in their outer chain moieties. However, the molar ratio of each oligosaccharide was different in each IgG sample, indicating that clonal variation is included in the sugar chain moieties of IgG molecules. One of the IgG2 contained four asparagine-linked sugar chains in one molecule, two on the Fc fragment and the remainder on the Fab fragment. The sugar chains in the Fc fragment contained much less galactose as compared with the Fab fragment.
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PMID:Structural study of the carbohydrate moieties of two human immunoglobulin subclasses (IgG2 and IgG4). 253 78

The superoxide-forming NADPH oxidase of resting macrophages can be activated in a cell-free system by certain anionic amphiphiles, most notably SDS. Activation requires the cooperation of membrane-associated and cytosolic components. We now report that at least two cytosolic factors are required for SDS-elicited activation of NADPH oxidase of guinea pig macrophages. Treatment of cytosol with ammonium sulfate at 37% saturation led to the partition of the two factors in the supernatant and precipitate fractions (termed components sigma 1 and sigma 2, respectively). Although each fraction by itself was inactive, recombining them resulted in complete recovery of the original ability of native cytosol to support SDS-elicited superoxide production by octyl-glucoside solubilized macrophage membranes. Both components are proteins, as shown by their susceptibility to trypsin and proteinase K, and were inactivated by heating at 60 degrees C. sigma 2, but not sigma 1, was inactivated by treatment with the covalent sulfhydryl reagent N-ethylmaleimide. On high-performance gel filtration, sigma 1 was found to have a molecular mass of 30 to 52 kDa, whereas sigma 2 eluted with molecules of 150 to 440 kDa. Component sigma 1 was partially purified from the ammonium sulfate supernatant fraction of cytosol by hydrophobic interaction chromatography followed by gel filtration. A material behaving like sigma 1 was also found to be present in the cytosol of guinea pig thymus cells, lymph node lymphocytes and brain and of the mouse myeloma cell line MOPC 315. However, sigma 2 appears to be strictly phagocyte specific. The molecular characteristics of sigma 1 components from nonphagocytic cells were similar to those of macrophage sigma 1, as shown by their presence in the supernatant, after treatment of cytosol with ammonium sulfate at 37% saturation, a molecular mass close to 30 to 52 kDa and a similar behavior on hydrophobic interaction chromatography. These findings raise the possibility that cytosolic component sigma 1 might be the bearer of a cellular function, more general than the one suggested by its role in the activation of NADPH oxidase of phagocytes.
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PMID:Activation of the superoxide-forming NADPH oxidase of macrophages requires two cytosolic components--one of them is also present in certain nonphagocytic cells. 255 80

We have prepared murine hybridomas secreting monoclonal antibodies against the exopopolysaccharide xanthan from Xanthomonas campestris pv. campestris 646 after fusing NSO myeloma cells and spleen cells from BALB/c mice immunized with xanthan. Four hybridomas, secreting antibodies designated A6 (IgM kappa), B3 (IgM kappa), D1 (IgM kappa), and D3 (IgG2A kappa), were selected for further studies. All antibodies reacted with a range of different xanthans. Competition studies using variants of the exopopolysaccharide as competitors suggested that specificity was mainly against the side-chain. One of the antibodies (B3) appeared to require the fully acylated side-chain with the pyruvylated terminal mannose as the immunodominant part. The three others were assumed to be directed against the nonsubstituted trisaccharide with the inner mannose-glucuronic acid being immunodominant. None of the antibodies reacted with cellulose (the xanthan backbone). Using immunoblotting techniques on nitrocellulose paper both a mixture of monoclonal antibodies, and also polyclonal ascitic fluid, could detect xanthan quantities of approximately 0.1 microgram.
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PMID:Monoclonal antibodies reacting with the exopolysaccharide xanthan from Xanthomonas campestris. 262 43

A comparative analysis of carbohydrate chains from human normal IgG and myeloma IgG (subclass 4) was carried out using HPLC. It is shown that both IgGs contain the same carbohydrate chains (biantennary and bisected) but the relative amount of bisected and incomplete chains (with fewer terminal galactose residues) is higher in myeloma IgG4. Two earlier unknown minor oligosaccharides were isolated from normal IgG and structurally studied by means of the partial hydrolysis and the Smith degradation.
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PMID:[Structural analysis of carbohydrate chains of normal and myeloma immunoglobulins G using HPLC]. 274 10

The rat myeloma cells chosen for study (IR202) are highly specialized toward the synthesis and secretion of immunoglobulin M (IgM). In [35S]methionine pulse-chase protocols the half-time for secretion of newly synthesized [35S]Ig at 37 degrees C is approximately 2 1/2 h. No degradation of [35S]Ig was detected in such experiments. Pulse-chase experiments with [3H]galactose show that addition of this terminal sugar occurs only approximately 2 min before discharge. The intracellular pool of Ig bearing mature oligosaccharides is therefore very small. Incubation at 20 degrees C stops secretion of the [35S]- and [3H]Ig. We describe a subcellular fractionation protocol for these cells which results in the recovery of a total microsomal fraction by gel filtration. This fraction includes approximately 1/4 of the galactosyltransferase and uridine diphosphatase (UDPase) of the homogenate. By employing two cytological Golgi markers (an "overosmicatable material" and UDPase), galactosyltransferase activity and [35S]methionine and [3H]galactose pulse-chase protocols with the chase at 15 degrees C we document the partial resolution of Golgi subcompartments in isopycnic sucrose gradients used to subfractionate the total microsomal fraction. Electron microscopic and enzymologic examination of the fractions resolved by these gradients confirm that rough microsomes are well separated from Golgi membranes and that the fractions most highly enriched in galactosyltransferase activity have a protein-based specific activity approximately 10 times that of the total microsomal fraction. These studies, therefore, form the basis for an analysis of the composition of the membranes of the Golgi Complex and document the location of proximal Golgi elements, as defined by cytological criteria, in isopycnic gradients.
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PMID:Biochemical, kinetic and cytochemical approaches resolve Golgi subcompartments of IgM-secreting rat myeloma cells. 274 93

Anionic amphiphiles such as long chain unsaturated fatty acids and SDS were shown to activate the superoxide (O2-) producing NADPH oxidase in a cell-free system derived from sonically disrupted phagocytes (macrophages and granulocytes). O2- production required the cooperation of a membrane associated component sedimenting at 48,000 X g (pi) and a cytosolic factor (sigma). The purpose of the present investigation was to find out whether components pi and sigma were also present in non-phagocytic cells that do not produce O2- when stimulated. It was found that the 48,000 X g pellets of guinea pig lymph node and thymus cell sonicates contained significant amounts of component pi, as shown by their ability to support SDS-elicited NADPH-dependent O2- production when supplemented with macrophage cytosol. Lymph node and thymus pi could be extracted from the membrane by 30 mM octyl glucoside, just as its macrophage-derived equivalent. Combining lymph node and thymus 48,000 X g pellet with autologous cytosol did not yield an active enzyme preparation. Also, cytosol from lymph node and thymus cells could not cooperate with macrophage 48,000 X g pellet, indicating that component sigma was lacking in lymphoid cells. Neither pi nor sigma could be detected in guinea pig kidney, the mouse myeloma cell line MOPC 315 and the canine cell line Cf2Th. The 48,000 X g pellet of all nonphagocytic cells examined contained a b-cytochrome that resembled, by its spectral characteristics, the cytochrome b559 thought to be characteristic of phagocytes. In macrophages, cytochrome b559 represented 80% of b-cytochrome content of the 48,000 X g pellet, whereas in non-phagocytic cells, the equivalent material represented only 50 to 60%. There was no correlation between the presence and quantity of the cytochrome b559-like chromophore in the 48,000 X g pellet of a particular cell type and its ability to cooperate with macrophage cytosol in SDS-elicited O2- production.
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PMID:Certain lymphoid cells contain the membrane-associated component of the phagocyte-specific NADPH oxidase. 283 Dec 70


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