Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two hybrid cell lines were prepared by the fusion of mouse myeloma cells with the spleen cells of BALB/c mice that had been immunized with the glycolipid ganglio-N-triosylceramide (asialo GM2). The specificity of the monoclonal antibodies produced by these hybridomas, one an IgM and the other an IgG3, has been defined by hemagglutination inhibition, complement fixation, and lysis of glycolipid liposomes by antibody and complement. A major determinant recognized by the IgM antibody is the nonreducing terminal N-acetylgalactosamine including the C6 primary hydroxyl group, but excluding the C2-acetamide group of N-acetylgalactosamine, because oxidation with galactose oxidase produced a structure showing only minimal cross-reaction with the IgM but replacement of the N-acetyl group with an N-n-butyryl group produced a glycolipid that reacts with IgM antibody to the same extent as with the unmodified glycoplipd. A major determinant recognized by the IgG3 antibody is the terminal N-acetylgalactosamine including the C2-acetamido group, but excluding the C6 primary hydroxyl group of N-acetylgalactosamine, because replacement of the N-acetyl group with an N-n-butyryl group produced a glycolipid that did not react with the IgG3 antibody; in striking contrast the IgG3 antibody reacted with the C6-oxidized glycolipid as well as with the native glycolipid. Neither antibody reacted significantly with any other natural glycolipids tested including several that are structurally related to asialo GM2 such as ganglioside GM2, ganglio-N-tetraosylceramide (asialo GM1), or ceramide dihexoside. These results indicated that in addition to the fine structure specificity described above both antibodies recognize the nonreducing terminal GalNAc beta 1 leads to 4Gal structure. The strict antigenic specificity of these monoclonal anti-glycolipid antibodies indicates their great potential as specific probes for cell surface studies.
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PMID:Production of monoclonal antibodies specific for two distinct steric portions of the glycolipid ganglio-N-triosylceramide (asialo GM2). 51 81

Immunization of mice with a synthetic GM3-lactam-BSA (bovine serum albumin) conjugate (designed to emulate the corresponding natural GM3-lactone conjugate), followed by fusion of splenocytes with myeloma cells, gave rise to more than 300 monoclonal hybridomas producing antibodies to GM3-lactam-BSA, which did not react with Glc-BSA and BSA. Eight antibody clones were randomly chosen from the positive 300 hybridomas. The eight clones, all belonging to the IgG class, were unreactive against GM3-ganglioside, whereas two antibodies (P5-1 and P5-3, both IgG1, kappa) reacted with GM3-ganglioside lactone. Binding of these two antibodies to the GM3-lactam-BSA conjugate was inhibited by soluble glycosides of GM2-, GM3-, and GM4-lactam and by GM3- and GM4-lactam, respectively, but not by Gb3 or asialo-GM1 and GM2-saccharides. A third antibody (P3; IgG2b, kappa) was inhibited by GM2-, GM3-, and GM4-lactam, but did not recognize GM3-ganglioside lactone.
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PMID:Anti-GM3-lactam monoclonal antibodies of the IgG type recognize natural GM3-ganglioside lactone but not GM3-ganglioside. 130 22

We generated two murine monoclonal antibodies (MAbs) specific for mono- and disialylgangliosides having N-glycolylneuraminic acid (NeuGc) as their sialic acid moiety, respectively, by immunizing C3H/HeN mice with these purified gangliosides adsorbed to Salmonella minnesota followed by fusion with mouse myeloma cells. By use of a wide variety of glycolipids, including NeuGc-containing gangliosides, the precise structures recognized by these two antibodies were elucidated through enzyme-linked immunosorbent assay and immunostaining on thin-layer chromatography. One MAb, GMR8, which was generated by immunizing the mice with purified GM3(NeuGc), reacted specifically with gangliosides having NeuGc alpha 2----3Gal- terminal structures, such as GM3(NeuGc), IV3NeuGc alpha-Gg4Cer, IV3NeuGc alpha-nLc4Cer, V3NeuGc alpha-Gb5Cer, and GD1a(NeuGc, NeuGc). None of the other gangliosides having internal NeuGc alpha2----3Gal- sequences, such as GM2(NeuGc) and GM1(NeuGc), nor corresponding gangliosides having NeuAc alpha 2----3Gal- sequences, nor neutral glycolipids were recognized. Thus, the epitope structures recognized by the MAb were found to be strictly NeuGc alpha 2----3Gal- terminal structures. In contrast, the other MAb, GMR3, which was generated by immunizing the mice with purified GD3(NeuGc-NeuGc-) adsorbed to the bacteria, reacted specifically with gangliosides having NeuGc alpha 2----8NeuGc alpha 2----3Gal- terminal sequences, such as GD3(NeuGc-NeuGc-), IV3NeuGc alpha 2-Gg4Cer, IV3NeuGc alpha 2-nLc4Cer, and V3NeuGc alpha 2-Gb5Cer, but did not react with corresponding gangliosides having NeuAc as their sialic acid moiety or with the neutral glycolipids tested. The epitope structures recognized by the MAb were suggested to be NeuGc alpha 2----8NeuGc alpha 2----3Gal- terminal structures. Using these MAbs, we determined the distribution of such gangliosides in the spleen, kidney, and liver of several mice strains. Novel gangliosides reactive with these MAbs were detected in these tissues.
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PMID:Generation of murine monoclonal antibodies specific for N-glycolylneuraminic acid-containing gangliosides. 156 98

We established five murine monoclonal antibodies (MAbs) specific for a-pathway ganglio-series gangliosides by immunizing C3H/HeN mice with these purified gangliosides adsorbed to Salmonella minnesota, followed by fusion with mouse myeloma cells. The binding specificities of these MAbs were determined by enzyme-linked immunosorbent assay and immunostaining on thin-layer chromatogram. These five MAbs, designated GMR6, GMB28, GMB16, GMR17, and GMR11 reacted strongly with the gangliosides GM3, GM2, GM1, GD1a, and GT1a, respectively, that were used as immunogens. Three MAbs, GMB28 (anti-GM2), GMB16 (anti-GM1), and GMR11 (anti-GT1a) showed highly restricted binding specificities, reacting only with the immunizing ganglioside. None of the other various authentic gangliosides or neutral glycolipids was recognized. On the other hand, the other two MAbs, GMR6 (anti-GM3) and GMR17 (anti-GD1a) exhibited broader specificities. MAb GMR6 cross-reacted with GM4, GM1b, GD1a, GT1b, and IV3NeuAc alpha-nLc4Cer. MAb GMR17 also reacted with GM1b and GT1b. Neither GMR6 nor GMR17 reacted with other gangliosides or neutral glycolipids tested. Using these MAbs, we determined the expression of these gangliosides, especially GM1, GD1a, and GT1a on mouse, rat and human leukemia cells. GM1 and GD1a were expressed on some leukemia cells, whereas GT1a was not detected in these cells.
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PMID:Generation of one set of monoclonal antibodies specific for a-pathway ganglio-series gangliosides. 162 99

Cell surface glycolipid expression as well as total glycolipid content of various B cell lines, representative of different B cell stages, and normal B lymphocytes were examined. Glycolipids, made up of a carbohydrate chain attached to a lipid called ceramide, are classified in four main 'series'. These series are defined according to the identity and chemical bonding of the sugars closest to the ceramide moiety. The pre-B cell lines contained lacto-series type II chain-based glycolipids and II3-alpha-N-acetyl-neuraminosyllactosylceramide (GM3) ganglioside. Upon differentiation, the lacto-series synthesis was shut down whereas compounds of the globo-series appeared: resting lymphocytes and lymphoblastoid cell lines (LCL) expressed GM3, globotriaosylceramide (Gb3), and globoside (Gb4). At a later stage of B cell differentiation, biosynthesis of the ganglio-series was extended and myeloma cells expressed II3-alpha-N-acetyl-neuraminosylgangliotriosylceramide (GM2). At the cell surface, in addition to Gb3, that we previously described as specifically expressed on Burkitt's lymphoma cells and on a subset of germinal centre tonsillar B cells, two glycolipids seemed specific of certain B cell lines: Gb4 was strongly positive on six out of eight LCLs and on the low buoyant density fraction of tonsillar B lymphocytes, whereas GM2 ganglioside was only detected on the two myeloma cell lines. These results, demonstrating the stage-dependent expression of certain glycolipids, suggest that these carbohydrate molecules could play functional roles during B cell differentiation.
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PMID:Sequential shifts in the three major glycosphingolipid series are associated with B cell differentiation. 177 23

The expression of neutral glycosphingolipids (GSL) in 37 B-cell neoplasms [7 acute lymphocytic leukemia (ALL), 5 Burkitt's lymphoma (BL), 7 chronic lymphocytic leukemia (CLL), 5 diffuse, poorly differentiated lymphoma (DPDL), 6 diffuse histiocytic lymphoma (DHL), 3 hairy-cell leukemia (HCL), and 4 multiple myeloma (MM)] was examined. Patterns of expression of simple (GlcCer, LacCer) and globo-series GSL (Gb3, Gb4) were found for each tumor type. In addition, pre-B ALL expressed the neo-lacto series GSL, paragloboside, which was not significantly seen at later stages of maturation. As a group, leukemias expressed about 10 times higher ratios of simple GSL to Globo-series GSL as compared to lymphomas, regardless of stage of differentiation. Significant amounts of GSL of other series were not found except in one CLL which contained asialo-GM2. GSL phenotype in these cells was not grossly affected by cell genotype since pre-B ALL containing Philadelphia chromosome t(9q;22q) translocations were similar to other ALL; and DHL with t(8q;14q) translocations had GSL patterns similar to other DHL samples and dissimilar to GSL patterns found in Burkitt's lymphomas with t(8q;14q). Differences in GSL expression among the different types of B-cell neoplasm suggested that GSL patterns form a phenotypic map that may complement the traditional glycoprotein immunophenotypic map and contribute to our understanding of the biology of these diseases and B-cell differentiation.
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PMID:Neutral glycosphingolipid expression in B-cell neoplasms. 195 88

GM2 ganglioside is a common cell surface constituent of human melanoma and other tumors of neuroectodermal origin, and vaccination with GM2 ganglioside results in high levels of anti-GM2 antibodies in patients with melanoma. Lymphocytes from a GM2-vaccinated patient (VS) were transformed by Epstein-Barr virus and tested for production of antibodies with reactivity for GM2-positive tumor cells. A high percentage of antibody-producing B cells was detected, but antibody reactivity was generally lost during culture expansion. Two cultures, however, remained stable for antibody productivity and one was used to develop a stable hybrid line with mouse myeloma. The monoclonal antibody (designated 3-207) derived from patient VS has dual specificity for GM2 and GD2, despite the fact that only GM2 antibody could be detected in the patient's serum. Monoclonal antibody 3-207 shows high-titered reactivity with a range of melanoma, astrocytoma, neuroblastoma, and leukemia cell lines, cells with prominent cell surface expression of GM2 and GD2. The cell surface reactivity of monoclonal antibody 3-207 was not abolished by treatment of target cells with neuraminidase, as the enzyme converted GD2 to GM2, which was still detected by monoclonal antibody 3-207.
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PMID:Human monoclonal antibody with dual GM2/GD2 specificity derived from an immunized melanoma patient. 215 45

Eleven monoclonal antibodies to GM1 ganglioside were prepared from hybridoma clones obtained by fusion of spleen cells from mice immunized with GM1 with mouse myeloma cells. When the reactivities of these 11 monoclonal antibodies were determined by enzyme-linked immunosorbent assay with six glycosphingolipids (GM1, GD1a, GD1b, GT1b, GM2, and asialo-GM1), they showed different degrees of specificity. From their reactivity patterns, they could be divided into three groups: Group 1, those that react only with GM1 (C3 and D3); Group 2, those that react predominantly with GM1 (C6, B6, D1, e1, g1, g9, and e12); and Group 3, those that show poor discrimination (h2 and A4). The clones differed in their biological activities.
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PMID:Preparation and specificity of 11 monoclonal antibodies to GM1 ganglioside. 242 55

Spleen cells from NZB mouse immunized with a membrane fraction of rabbit thymus tissue were fused with BALB/c 6-thioguanine-resistant myeloma cells, P3-X63-Ag8.653. One hybridoma clone (Y-2-HD-1) produced IgM immunoglobulin that bound to an N-glycolylneuraminic acid-containing GM2 ganglioside, GM2(NeuGc), which is known to be a Hanganutziu-Deicher antigen. The specificity of the Y-2-HD-1 monoclonal antibody was examined, using authentic glycosphingolipids structurally related to GM2(NeuGc), by means of an enzyme-linked immunosorbent assay and thin-layer chromatography/enzyme immunostaining, respectively. The monoclonal antibody was found to be highly specific to GM2(NeuGc) and the epitope was a non-reducing terminal GalNAc beta 1-4[NeuGc alpha 2-3]Gal structure. This monoclonal antibody (Y-2-HD-1) bound to native mouse erythrocytes, in which GM2(NeuGc) is a major ganglioside. These results indicate that GM2(NeuGc) is located on the surface of mouse erythrocytes.
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PMID:Monoclonal antibody directed to a Hanganutziu-Deicher active ganglioside, GM2 (NeuGc). 244 47

The fine specificity analysis of two human monoclonal antibodies (AbFCM1 and AbHJM1) reacting with gangliosides is described and their specificities are compared with analogous mouse monoclonal antibodies (mAbs). These two antibodies were generated from lymphocytes of melanoma patients by Epstein-Barr virus transformation followed by fusion with mouse myeloma NS-1. Using a wide variety of gangliosides, including N-glycolylneuraminic acid (NeuGc)-containing compounds, the precise structures recognized by these two antibodies were elucidated by enzyme-linked immunosorbent assay and immunostaining of thin-layer chromatograms. AbFCM1 reacted with N-acetylneuraminic acid (NeuAc)-type GM3, GD1a, sialylparagloboside, and GT1b in decreasing order of intensity. This antibody also reacted with (NeuAc-NeuGc-)-GD3 and -disialylparagloboside, but did not react with NeuGc-type GM3, GM2, sialylparagloboside, (NeuGc)2-GD3 and -disialylparagloboside. The main epitope structures recognized by AbFCM1 are, therefore, NeuAc alpha 2----3Gal beta 1- and NeuAc alpha 2----8NeuGc alpha 2----Gal beta 1-. These results are similar to the specificity of mouse mAb M2590. AbHJM1 reacted with NeuAc-type GD3 and disialylparagloboside, GD2, GD1b, GM3, and GT1b, in decreasing order of intensity. Among NeuGc-type gangliosides, this antibody reacts with (NeuAc-NeuGc-)-GD3 and -disialylparagloboside, but did not react with gangliosides containing only NeuGc. Consequently the epitope structure recognized by AbHJM1 is probably (R)-(NeuAc alpha 2----8Sialic acid alpha 2----3)Gal beta 1-. Mouse anti-GD3 mAbR24, in contrast, showed strong reactivity only with GD3 and -disialylparagloboside among NeuAc-type gangliosides, but showed a similar pattern to AbHJM1 in its reactivity with NeuGc-containing gangliosides. Although these two human monoclonal antibodies are not highly restricted in their specificities, they reacted best with the major gangliosides, GM3 and GD3, present in the majority of human melanomas.
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PMID:Two human monoclonal antibodies reacting with the major gangliosides of human melanomas and comparison with corresponding mouse monoclonal antibodies. 290 45


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