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)

Acquisition of carbohydrates in the disulfide-linked heavy (H) and light (L) chain molecules of murine myeloma (ADJPC5), i.e., HH, HHL, and LHHL, was investigated. That some mannose and glucosamine residues are acquired by immunoglobulin precursor molecules was demonstrated by the detection of glucosamine and mannose in HH, HHL, and LHHL. In contrast, galactose was observed solely in LHHL molecules, which have an identical electrophoretic mobility to the secreted product. Furthermore, as judged from cells incubated with [(3)H]leucine, the more juvenile molecules HH and HHL were predominant in the rough microsome fraction, whereas LHHL was the principal molecular species in the smooth microsome fraction. Findings of this type were not observed in rabbit lymph node cells. Thus, galactose, as well as mannose and glucosamine, were found in the more juvenile molecule known for this species (HL). Moreover, the ratio of HL:LHHL, as judged from cells incubated with [(3)H]leucine, was about the same in rough and smooth microsomes.
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PMID:Synthesis and secretion of gammaglobulin by lymph node cells: the acquisition of carbohydrate residues of immunoglobulin in relation to interchain disulfide bond formation (heavy and light chains-murine myeloma-mannose-glucosamine-galactose). 410 96

The carbohydrate content of an A myeloma globulin was investigated. The carbohydrate content was found to be unchanged when the protein was isolated from the patient over a period of 18 months. The various polymeric forms of the protein contained similar proportions of carbohydrate. The A myeloma globulin contained approx. 2 residues of 6-deoxy-l-galactose (l-fucose), 14-15 of d-mannose, 12-13 of d-galactose, 12-13 of 2-acetamido-2-deoxy-d-glucose (N-acetyl-d-glucosamine), 6 of 2-acetamido-2-deoxy-d-galactose (N-acetyl-d-galactosamine) and 5 of N-acetylneuraminic acid (sialic acid), and these were distributed between six oligosaccharide units all of which were present on the heavy polypeptide chains. The oligosaccharide units showed two kinds of heterogeneity, which have been termed central and peripheral. Central heterogeneity was shown by the presence of three completely different core units, which had the following compositions: (1) 3 residues of d-galactose and 3 of 2-acetamido-2-deoxy-d-galactose, joined to protein by an O-glycosidic linkage between acetamidohexose and serine; (2) 3 residues of d-mannose, 2 of d-galactose and 3 of 2-acetamido-2-deoxy-d-glucose, joined to protein by an N-glycosidic linkage between acetamidohexose and aspartic acid; (3) 4 residues of d-mannose and 3 of 2-acetamido-2-deoxy-d-glucose with a linkage similar to that in (2). The core oligosaccharide units showed peripheral heterogeneity in the attachment of 6-deoxy-l-galactose, 2-acetamido-2-deoxy-d-glucose and N-acetylneuraminic acid. Tentative structures are proposed for these various types of oligosaccharide unit. Glycopeptides were isolated in which the sialic acid content exceeded that of d-galactose. Explanations are given for the electrophoretic mobility and staining characteristics of the various glycopeptides.
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PMID:Investigations on the oligosaccharide units of an A myeloma globulin. 417 99

Incorporation of radioactive fucose into the immunoglobulin G1 myeloma protein secreted by mouse plasma-cell tumour MOPC 21 is stereospecific for the l-isomer. Heavy chains of the secreted form of the myeloma protein carry 90% of the label in fucose residues of their carbohydrate moieties. A small but significant amount of the intracellular immunoglobulin G1 of the mouse plasma-cell tumour MOPC 21 appears to be labelled. Serum in the incubation medium supplies low-molecular-weight diffusible substances necessary to maintain continuous secretion of fucose-labelled myeloma protein beyond 2-3h, and of leucine-labelled myeloma protein beyond 6-8h. In medium containing extensively dialysed serum the secretion of leucine- and fucose-labelled myeloma protein can be restored by the addition of 250mum-d-mannose, 250mum-d-galactose and 250mum-glucosamine. Synthesis and secretion appear to be facilitated in the presence of these sugars, although secretion of myeloma protein devoid of terminal fucose residues is possible for a limited time-period.
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PMID:Biosynthesis of the carbohydrate portion of immunoglobulins. Incorporation of radioactive fucose into immunoglobulin G1 synthesized and secreted by mouse plasma-cell tumour MOPC 21. 515 9

Mouse myeloma cells were pulse-labeled in vitro with (3)H-D-glucosamine and (14)C-L-leucine. Analysis on sucrose gradients revealed incorporation of both isotopes into polyribosomes and release of most of such radioactivity after treatment of labeled cells in vitro with puromycin. A mixing experiment excluded the in vitro binding to unlabeled polyribosomes of (3)H-glucosamine in labeled post-ribosomal material. Polyribosomes labeled with (3)H-glucosamine were precipitated with antiserum specific for mouse immunoglobulin. By chromatography and gel filtration, the precipitable radioactivity was shown to be glucosamine covalently bound to heavy and light chains.
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PMID:Immunoglobulin synthesis and secretion. 3. Incorporation of glucosamine into immunoglobulin on polyribosomes. 526 20

Mouse myeloma cells pulse-labeled in vitro with (3)H-leucine or (3)H-glucosamine were fractionated on sucrose gradients, and membrane-bound and free polyribosomes were separated. Nascent polypeptides released from polyribosomes were precipitated with antiserum specific for mouse immunoglobulin. The results indicate that immunoglobulin is synthesized preferentially by bound polyribosomes.
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PMID:Immunoglobulin synthesis and secretion. V. Incorporation of leucine and glucosamine into immunoglobulin on free and bound polyribosomes. 527 48

This study was designed to determine the time in the intracellular life of immunoglobulin when the carbohydrate moieties are added. Plasma cells from a mouse myeloma tumor were exposed to glucosamine-(3)H (a "bridge" sugar), galactose-(3)H, or leucine-(3)H. With each of the above isotopes, the percentage of total radioactive immunoglobulin that has been secreted after different periods of labeling and the extent to which puromycin prevented incorporation into immunoglobulin were determined. The results indicate that both galactose and glucosamine (in its N-acetyl form) become covalently incorporated into immunoglobulin G late in its intracellular life and suggest that glucosamine is also added onto nascent polypeptide chains (i.e., on polyribosomes).
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PMID:Immunoglobulin synthesis and secretion. I. Biosynthetic studies of the addition of the carbohydrate moieties. 545 11

The subcellular sites of synthesis and route of intracellular transfer of immunoglobulin G (IgG) have been investigated by electron microscope radioautography with precursors used for the polypeptide chain (leucine-(3)H) and for the carbohydrate moieties (galactose-(3)H and glucosamine-(3)H). For this purpose, plasma cells from a mouse myeloma tumor were labeled with appropriate precursors and the distribution of radioautographic grains was determined at the end of the labeling period and after varying times of incubation in unlabeled medium. The results indicated that the polypeptide backbone is synthesized in a region of the cell occupied by the rough endoplasmic reticulum (RER) and is transported from there to the region of the Golgi complex. Galactose is incorporated in IgG primarily at the level of the Golgi complex, whereas the incorporation of glucosamine appears to take place both in the RER and in the Golgi complex. From the Golgi complex, the completed IgG molecules reach the plasma membrane and are discharged extracellularly. The latter route of transport and the mechanism of discharge are not understood but may be mediated via smooth-surfaced vesicles.
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PMID:Immunoglobulin synthesis and secretion. II. Radioautographic studies of sites of addition of carbohydrate moieties and intracellular transport. 546 Apr 63

We have produced lymphocyte hybridomas between mouse myeloma cells and either spleen cells of C3H/f/C57BL/6 mice bearing the Mm5mt/c1 tumor-producing murine mammary tumor virus (MMTV) or spleen cells from Fisher rats inoculated with the same tumor. Two classes of hybridoma-secreted monoclonal antibodies were obtained. In the first class are IVC11, IIIA1, and VE7, each of which precipitated a 52,000-dalton protein from 125I-labeled purified preparations of MMTV and [3H]glucosamine-labeled Mm5mt/c1 cell extracts. A second class of monoclonal antibodies, represented by IC12 and IIIB5, reacted specifically with C3H MMTV-secreting cells in radioimmunoassays (RIA) with whole cells and did not precipitate proteins with labeled virus or metabolically labeled Mm5mt/c cell extracts. IC12 and IIB5 could be distinguished from each other in a RIA in which antigen discs were prepared from a membrane preparation of Mm5mt/c1 cells. In this assay, IC12 antibody was blocked from reacting with discs precoated with goat anti-MMTV, and IIB5 antibody was not.
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PMID:Monoclonal antibodies against antigens displayed on a progressively growing mammary tumor. 626 47

A variant line (LV-1) of mouse myeloma MOPC 315 (IgA, lambda 2) has lost the ability to synthesize L chain. It synthesizes an altered H chain (H' chain) that is turned over intracellularly and is not secreted. Rescue of H' chain secretion can be accomplished by fusion of LV-1 to a variant of another myeloma line, MPC 11 (IgG2b, kappa), which only synthesizes a light chain. The hybrid (X-2) secretes the H' chain in a four chain structure (kappa 2 alpha' 2). In wild-type MOPC 315 cells, it was reported previously that inhibition of core sugar addition blocks the secretion of the H chain polypeptide. We have studied glycosylation in MPOC 315 wild-type, LV-1 variant, and X-2 hybrid cell lines. The ability of all three lines to add the core sugars mannose and glucosamine to heavy chain was demonstrated. Due to the instability of the H' chain in LV-1, it is difficult to assess H' chain fucosylation directly. To study fucose addition in LV-1, the enveloped virus vesicular stomatitis (VSV), which can infect the three lines, was utilized. The fucosylation and secretion of VSV glycoprotein G was discernible in all three lines; however, only LV-1 cannot activate free fucose, and instead fucosylates through conversion of the mannose intermediate. Normal fucose addition to H chain in a wild-type cell occurred immediately before secretion. The fact that degradation of H' chain in LV-1 begins before fucosylation suggests that the rescue of H' chain secretion by formation of the X-2 hybrid is due to the acquired presence of a suitable L chain rather than complementation of a sugar defect. These observations indicate that proper assembly of the polypeptide components of some secretory proteins, e.g., Ig molecules, is required for the secretion of the individual chains.
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PMID:Glycosylation and secretion of an altered immunoglobulin heavy chain in mouse myeloma MOPC 315. 629 92

The capacity of Plasmodia to synthesize sialic acids was investigated by adding radioactive acetate to short-term in vitro cultures of the intraerythrocytic asexual forms of three malaria parasites (the human malaria Plasmodium falciparum in Aotus trivirgatus erythrocytes; the simian malaria P. knowlesi in rhesus monkey erythrocytes; the rodent malaria P. berghei in mouse erythrocytes) and to cultures of extracellular zygotes of the avian malaria P. gallinaceum. Radioactive acetate was added to normal rhesus monkey erythrocytes and to cells of the murine myeloma NS-1 for comparison. Although [1-14C]-acetate labeled many proteins with each malaria parasite and the NS-1 cells, analysis of purified sialic acids revealed that only with the NS-1 cells was radioactivity incorporated into sialic acids. Furthermore, N-acetyl[6-3H]mannosamine was not incorporated into sialic acids or malarial glycoproteins when added to P. knowlesi cultures. All of the malaria parasites underwent growth or differentiation during these experiments as measured by [35S]methionine uptake into protein and by light microscopy. Extracellular parasites largely free of erythrocyte membranes were prepared to determine whether Plasmodia contain sialic acids that are not labeled by exogenous precursors. Purified merozoites of P. knowlesi and zygotes of P. gallinaceum did not contain detectable amounts of sialic acids on chemical analysis. Thus, although we could show that Plasmodia can incorporate radioactive sugars such as glucosamine, galactose and mannose into proteins, presumably glycoproteins, they do not synthesize sialic acids or sialo-glycoproteins, nor do they contain sialo-glycoconjugates of host origin.
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PMID:Malaria parasites do not contain or synthesize sialic acids. 637 Aug 20


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