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)

High field magnetic resonance spectroscopy has been utilized to deduce the primary structure of the glycopeptides from a human myeloma gamma 1-immunoglobulin G (Tem). The major structures found belong to the biantennary complex class of glycopeptides, with a minor (5%) fraction belonging to the bisected biantennary complex class. In the biantennary class, three structures were present with different residues at the termini of the alpha Man(1-6) and alpha Man(1-3) arms: (i) with beta Gal(1-4) and alpha NeuNAc(2-6), respectively (33%); (ii) with beta Gal(1-4) and beta Gal(1-4), respectively (45%); and (iii) beta Gal(1-4) and beta GlcNAc(1-2), respectively (17%). In the bisected biantennary class only the latter termini were found for the two arms. These results suggest that the galactosyl transferase in these cells has a preference for the beta GlcNAc(1-2) of the alpha Man(1-6) arm and that the sialyltransferase has a preference for the beta Gal(1-4) of the alpha Man(1-3) arm.
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PMID:Structure of the glycopeptides of a human gamma 1-immunoglobulin G (Tem) myeloma protein as determined by 360-megahertz nuclear magnetic resonance spectroscopy. 716 34

Pure secretory immunoglobulin A was isolated from human milk by fractionation in gradients of pH and (NH4)2SO4 concentration followed by gel filtration. The hinge region containing all the O-glycosidically linked oligosaccharides was isolated en bloc after trypsin and pepsin hydrolysis and separated by gel filtration. The mixture of O-glycosidically linked oligosaccharides contained N-acetylneuraminic acid (NeuAc), fucose (Fuc), galactose (Gal), N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc) in the molar ratio of 0.2:0.5:2.5:2:1 respectively. After beta-elimination several oligosaccharides were separated by a combination of ion-exchange chromatography and gel-filtration chromatography. The complete structure of four of these oligosaccharides was determined by methanolysis, methylation and mass spectrometry. The structure of the four oligosaccharides which are linked to serine or threonine residues of the hinge region are as follows: beta-Gal-(1 leads to 3)-GalNAc-ol; alpha-HeuAc-(2 leads to 3)-beta-Gal-(1 leads to 3)-GalNAc-ol; beta-Gal-(1 leads to 3)-[beta-GlcNAc-(1 leads to 6)]-GalNAc-ol; beta-Gal-(1 leads to 3)-[beta-Gal-(1 leads to 4)-beta-GlcNac-(1 leads to 6)]-Gal-NAc-ol. These oligosaccharides are more complex and heterogenous than the oligosaccharides linked to serine residues of the hinge region from myeloma serum immunoglobulin A1.
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PMID:Heterogeneity of the glycans O-glycosidically linked to the hinge region of secretory immunoglobulins from human milk. 721 51

The specificity of guinea-pig- and carp-anti-idiotypic antisera were compared by using the radioimmunoassay and the passive hemagglutination inhibition test. Guinea-pigs and carps were immunized with the IgA/k mouse myeloma protein S117 which has binding activity to the hapten N-acetylglucosamine. the resulting antisera were idiotypically specified by absorption and the activity was determined by the binding of the radiolabeled idiotype S117. The binding curves of guinea pig and carp anti-idiotypic antisera are very similar. The idiotype-anti-idiotype reaction could be partially inhibited by the specific hapten N-acetylglucosamine but not by N-acetylgalactosamine. Both antisera, guinea pig and carp, respectively, are different in respect to the immunoglobulin class of anti-idiotypic antibodies which react with the idiotype S117. In the case of the guinea pig antisera the anti-idiotypic antibodies are mainly of the IgG-type whereas the anti-idiotypic antibodies of carp are exclusively of IgM-type. This important difference is discussed.
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PMID:[Comparative studies of the specificity of idiotypic guinea pig and carp antisera]. 742 49

Changes in the activity and transcription of UDP-N-acetylglucosamine: beta-D-mannoside beta-1,4-N-acetylglucosaminyl-transferase III (GnT-III: EC 2.4.1.144) were investigated in haematological malignancies. GnT-III activity was elevated in patients with chronic myelogeneous leukaemia in blast crisis (CML-BC) and patients with multiple myeloma (MM); whereas most of the normal healthy subjects and patients with other haematological malignancies, including CML in its chronic phase, showed negligible activity. The GnT-III transcript of leukaemic cells from various haematological diseases showed a single band with a similar size. The ratio of GnT-III activity per normalized transcript in CML-BC was considerably higher than in the other conditions, which provided the possibility that in CML-BC the transcript or the enzyme protein might be more stable, or that a post-translational modification of the enzyme might enhance its activity. Furthermore, a lectin blot analysis of patient specimens and a lectin fluorescence study of CML cell lines revealed that E4-PHA binding to surface glycoproteins correlated with GnT-III activity, indicating that more bisecting GlcNAc was added to these glycoproteins, catalysed by elevated GnT-III in CML-BC.
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PMID:Changes of beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) in patients with leukaemia. 749 37

Two chimeric human/murine monoclonal antibodies were constructed by substitution of the murine constant regions with human gamma 1 and kappa constant regions for heavy and light chains, respectively. The chimeric human/murine molecules are anti-idiotypic antibodies, meaning that they were directed against the antigen binding site in the variable region of another antibody. Antibody batches were produced under identical production conditions, using two selected SP2/0 myeloma cell subclones, which produce chimeric antibodies with different variable regions, but identical constant regions. Several samples were collected during the production of the antibodies in hollow-fibre reactors. The heavy chain, but not the light chain, of the two different chimeric IgG1 antibodies is glycosylated. Structural analysis of the enzymically released N-linked carbohydrate chains by 1H-NMR spectroscopy, as well as by chromatographic profiling, demonstrated that the collection of N-glycans comprises a small amount of monoantennary, and for the greater part diantennary structures. The N-glycans are completely (alpha 1-->6)-fucosylated at the innermost GlcNAc residue. The antennae of the neutral diantennary N-glycans are built up from GlcNAc beta 1-->2, Gal beta 1-->4GlcNAc beta 1-->2 or Gal alpha 1-->3G alpha 1 beta 1-->4GlcNAc beta 1-->2 elements, whereas the antennae of the neutral monoantennary carbohydrate chains have only (beta 1-->2)-linked GlcNAc residues. Galactosylation of the GlcNAc beta 1-->2Man alpha 1-->6 branch occurs four times more frequently than that of the GlcNAc beta 1-->2Man alpha 1-->3 branch, independently of the production batch. A small amount of the diantennary N-glycans are mono- or disialylated, carrying N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), exclusively (alpha 2-->6)-linked to beta Gal. Analysis of the different production batches demonstrates that the structures of the N-linked carbohydrate chains are identical in the two chimeric antibodies, but that the relative amounts of the major oligosaccharide components, the degree of sialylation and the molar ratio of Neu5Ac to Neu5Gc varies with the SP2/0 cell subclone, and only slightly with cell age.
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PMID:Variation in N-linked carbohydrate chains in different batches of two chimeric monoclonal IgG1 antibodies produced by different murine SP2/0 transfectoma cell subclones. 749 47

The activity and mRNA expression of UDP-N-acetylglucosamine: beta-D mannoside beta-1,4-N-acetylglucosaminyl transferase III (GnT-III: EC 2.4.1.144) were investigated in hematological malignancies. GnT-III activity was elevated in patients with chronic myelogenous leukemia (CML) in blast crisis and patients with multiple myeloma (MM), as compared to normal healthy subjects and patients with other hematological malignancies including CML in chronic phase. The GnT-III transcript was the same size in leukemic cells from various hematological diseases and cell lines, while expression of the transcript was not found to correlate significantly with enzyme activity, implying that post-translational modification might regulate the activity of GnT-III. Southern-blot analysis showed no significant variation in the structure and position of the GnT-III genome, indicating that the gene is present as a single copy without isoforms. Furthermore, analyses by immunoprecipitation and Western blot revealed that high GnT-III activity in KU812 cell, a CML cell line, resulted in an increase in E4-PHA binding to CD45, a major surface glycoprotein of the leukocyte, indicating that more bisecting GlcNAc was added to CD45 catalyzed by elevated GnT-III.
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PMID:High expression of UDP-N-acetylglucosamine: beta-D mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) in chronic myelogenous leukemia in blast crisis. 782 56

This study characterized the N-glycans of a humanized immunoglobulin G4 (IgG4) expressed in NS/O mouse myeloma cells and directed against the CD18 family of adhesion-promoting receptors on leukocytes. The N-glycans were released from the purified recombinant IgG by N-glycanase treatment, purified by Sephadex G50 chromatography, and fractionated by Bio-Gel P-4 chromatography into three oligosaccharide pools. Each pool was analyzed individually by glycosyl composition analysis, high-pH anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD), 600-MHz 1H-NMR spectroscopy, and electrospray-ionization mass spectrometry. In addition, each of the three pools was subfractionated by HPAEC and the isolated subfractions that contained sufficient material were hydrolyzed and analyzed for glycosyl composition by HPAEC-PAD. The overall results indicate the presence of five oligomannoside-type structures (containing 5 to 8 Man residues) which are not usually found in IgG, and the presence of eight diantennary (mostly truncated) N-acetyllactosamine-type structures which are typical of mouse and human IgGs. The N-acetyllactosamine-type structures were heterogeneous with regard to alpha(1-->6) fucosylation of the linkage GlcNAc, and the presence or absence of GlcNAc and/or Gal beta(1-->4)GlcNAc extending the core pentasaccharide (Man3GlcNAc2). No evidence was found for the presence of sialic acid or bisecting GlcNAc residues on the N-acetyllactosamine-type chains. The latter finding suggests that the N-glycans of this humanized IgG are of the mouse type.
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PMID:Structural characterization of the N-glycans of a humanized anti-CD18 murine immunoglobulin G. 790 4

Cell-surface sugar receptors may participate in interactions of lymphoid cells that influence their adhesive properties and proliferation. Their expression on cells of the pre-B line BLIN-I, the B-lymphoblastoid line Croco II, the myeloma line RPMI 8226 and the T-lymphoblastoid line CCRF-CEM was monitored with a panel of 14 types of chemically glycosylated E. coli beta-galactosidase at a non-saturating ligand concentration. Quantitative differences were determined for the capacity of the different cell types to bind constituents of the carbohydrate part of glycoconjugates. They were corroborated by analyses of binding for lactose-, beta-N-acetylgalactosamine-, beta-N-acetylglucosamine- and fucose-exposing neoglycoenzymes up to saturation levels. Values of dissociation constants of the tetrameric enzyme were in the range of 3-300 nM. Several types of sugar receptor led to carbohydrate-inhibitable adhesion of cells to 6 types of nitrocellulose-immobilized neoglycoprotein, their effectiveness being most obvious for the myeloma cells. Analyses of the carbohydrate-ligand-mediated adhesion of the other cell types revealed a comparatively decreased response. Only a few carbohydrates among the 7 types tested were effective in reducing cell adhesion to a far more complex ligand-bearing matrix than immobilized neoglycoproteins, namely bone-marrow stromal cell layers: sialic acid and N-acetylgalactosamine for B-lymphoblastoid cells and rhamnose for pre-B cells. These cellular interactions may encompass sugar receptors on the stromal cells and other types of molecular recognition in addition to the detected activities on the lymphoid cells.
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PMID:Adhesion of human lymphoid cell lines to immobilized carbohydrates and to bone-marrow stromal cell layers by surface sugar receptors. 839 77

Sialylated oligosaccharide structures were determined by the technique of electrospray ionization mass spectroscopy at seven of eight N-linked glycosylation sites of recombinant human ICAM-1des454-532 [tICAM(453)] purified from the tissue culture fluid of Chinese hamster ovary, human embryonic kidney, and mouse myeloma cell lines. The number of structures at each site depended on the cell line and ranged from 8 to 34. N-Glycolyneuraminic acid, a human oncofetal antigen, was found at all sites of all three cell line derived forms of tICAM(453). Tetraantennary complex structures containing one and/or two galactose-beta 1,4 N-acetylglucosamine repeats, characteristic of membrane bound proteins, were found on soluble tICAM(453) primarily at Asn-379. Asn-379, located between the D4 and D5 domains, is believed to be located close to the membrane surface in membrane bound ICAM-1. It has been proposed that the extent of N-linked glycosylation at Asn-240 and Asn-269 in the third domain of ICAM-1 may regulate the binding avidity of ICAM-1 to Mac-1 [Diamond, M. S., Staunton, D. E., Marlin, S. D., & Springer, T. A. (1991) Cell 65, 961-971]. In the present study the tICAM(453) Asn-269 site was found to contain predominantly one oligosaccharide structure that is conserved in all three cell lines. On the other hand, the Asn-240 site was found to contain cell line dependent oligosaccharide structural heterogeneity particularly in the degree of sialylation.
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PMID:Cell line and site specific comparative analysis of the N-linked oligosaccharides on human ICAM-1des454-532 by electrospray ionization mass spectrometry. 863 67

A complete immunochemical and molecular profile was generated for a group of hybridoma and myeloma antibodies bearing the A48 regulatory idiotype (RI). These A48 RI+ antibodies were derived from normal or idiotypically manipulated mice and were selected either for utilization of a VHX24 VH gene or expression of the A48 RI. Among the hybridomas selected for VHX24 VH utilization a variety of antibody specificities were seen with the fructosan specificity occurring least frequently and the N-acetylglucosamine specificity occurring most frequently. A variety of Vk families were used with a bias for the Vk1 family by the antibodies deriving from untreated mice. The A48RI was expressed by only 3 of these antibodies, none of which were fructan specific. Two used the canonical VHX24-Vk10 combination utilized by the A48 and UPC 10 prototypes, and one used the VHX24-Vkl combination. This demonstration of A48 RI expression ny non-fructan specific, non-VHX24+Vk10+ antibodies was extended by showing expression of this Id by two monoclonal antibodies specific for the Sm self-antigen, one rheumatoid factor and two monoclonal antibodies specific for influenza virus hemagglutinin molecule. They used different VH-VL combinations. Among the monoclonal antibodies selected for A48 RI expression all exhibited fructan binding activity and the vast majority used the VHX24-Vk10 association. A collective analysis of the VH and VL sequences of all these A48RI+ antibodies showed idiotype expression was not associated with any particular germline VH or VL gene. D, Jk or JH sequence. Three positions on the light chain and one on the heavy chain were identified which could represent the structural correlates for the A48 regulatory idiotype.
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PMID:The molecular origin of regulatory idiotypes. 869 Oct 44


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