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)

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

A new monoclonal antibody (NS24) directed to the N-acetylneuraminyl alpha 2-3Gal beta 1-4GlcNAc residue in type II sugar chain of N-acetylneuraminyllactoneotetraosylceramide [sialylparagloboside, IV3(NeuAc)nLc4Cer] was prepared by hybridoma technique. Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol, IV3(NeuAc)nLc4Cer, and lipopolysaccharides from Salmonella minnesota R595 were used for immunization with IV3(NeuAc)nLc4Cer isolated from human erythrocytes. This method allowed the fusion of spleen cells of immunized mouse with myeloma cells only three days after immunization. NS24 reacted specifically to both naturally occurring and chemically synthesized IV3-(NeuAc)nLc4Cer, whereas it has no reactivity to structurally related gangliosides, such as IV6(NeuAc)nLc4Cer, N-glycolylneuraminyl alpha 2-3lactoneotetraosylceramide [IV3(NeuGc)-nLc4Cer], i-active ganglioside [VI3(NeuAc)nLc6Cer], I-active ganglioside [VIII3(NeuAc)-VI3(NeuAc)IV6kladoLc8Cer], GM4(NeuAc), GM3(NeuAc), GM3(NeuGc), GM1b(NeuAc), GD3-(NeuAc), other ganglio-series gangliosides, sulfatide, and paragloboside (nLc4Cer). Synthetic N-acetylneuraminyl alpha 2-3lactotetraosylceramide [IV3(NeuAc)Lc4Cer] and its asialo-derivative (Lc4Cer) carrying type I sugar chain also showed no reaction with NS24. One to 100 pmol of IV3(NeuAc)nLc4Cer was detected dose-dependently by a thin-layer chromatography/enzyme immunostaining procedure. Human gastric carcinomas showed positive reactions with NS24 immunochemically and histochemically. NS24 reacted preferentially with poorly differentiated adenocarcinomas rather than well differentiated ones.
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PMID:A new monoclonal antibody directed to sialyl alpha 2-3lactoneotetraosylceramide and its application for detection of human gastrointestinal neoplasms. 186 48

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

We have established a human-human hybridoma producing a monoclonal antibody against a tumor-associated carbohydrate-specific antigen, Hanganutziu-Deicher (HD) antigen. Human spleen lymphocytes from a patient with esophageal varices complicated with liver cirrhosis were cultured in serum-free medium and co-stimulated with both anti-human mu-chain antibodies and supernatants of concanavalin A-stimulated human spleen cell culture (ConA sup). The activated lymphocytes were subsequently primed in vitro with particulate HD3 antigen and fused with a parent hybrid myeloma cell line, KR-12. A hybridoma, 1F43E31G7 produced anti-HD human monoclonal antibody (IgM lambda). This monoclonal antibody reacted strongly with N-glycolylneuraminyl alpha 2-3 lactosylceramide (HD3) and slightly with N-glycolylneuraminyl alpha 2-3 lactoneotetraosylceramide (HD5), but did not react with N-glycolylneuraminyl alpha 2-3 lactoneohexaosylceramide (HD7), N-acetylneuraminyl alpha 2-3 lactosylceramide (GM3) and other derivatives of HD3 prepared by chemical modification of the sialic acid residue of HD3, which indicates that the monoclonal antibody is directed precisely toward the terminal sialic acid and whole structure of HD3.
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PMID:Establishment of a human monoclonal antibody to Hanganutziu-Deicher antigen as a tumor-associated carbohydrate antigen. 314 5

A monoclonal antibody (MAb) was prepared by the fusion of murine SP2-O myeloma cells with BALB/cByJ spleen cells that were immunized with the glycolipid asialo GM1 adsorbed to naked Salmonella. The specificity of the IgM antibody obtained was defined using various glycolipids, cell extracts and saccharides in ELISA assays and thin-layer chromatography (TLC) immunoblots. The non-reducing terminal galactose is the immunodominant residue for this antibody; however, there is undetectable reactivity to free galactose, galactosylceramide or compounds with an alpha-linked galactose. The SH-34 antibody specifically lyses asialo GM1-expressing macrophages in the presence of complement and removes NK cells in vitro from spleen cell populations. When the specificity of the MAb was compared to that of a commercially available rabbit antiserum to asialo GM1, it was found that both cross-reacted with GM1 and asialo GM3 at high antibody concns; however, the MAb did not bind asialo GM2 while the rabbit antiserum showed substantial reactivity to this glycolipid. It is anticipated that this MAb will be useful for the study of murine and rat natural killer cells.
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PMID:A monoclonal antibody with reactivity to asialo GM1 and murine natural killer cells. 361 6

In this study gangliosides from various myelomas and hybridomas of mouse, rat, and human origin were characterized by thin-layer and high-performance liquid chromatography, immunological methods (overlay technique) and fast atom bombardment mass spectrometry. Exclusively GM3 substituted with C24:1- and C16:0-fatty acid, was found in all B cell-derived cell lines. C18 sphingosine was the single long chain base in each GM3 ceramide portion. The mouse myeloma (NS-1) and all hybridomas, obtained by fusion of mouse, rat, or human B lymphocytes with murine myelomas, showed high GM3 (NeuGc) content (> 75%) and low GM3 (NeuAc) expression. Absolute amounts of GM3 ranged from 0.2 up to 0.8 mg x 10(-9) cells. Normally, human cells do not express NeuGc, and an Epstein-Barr virus-transformed human B lymphocyte line analyzed in this study retained this sialylation status, expressing exclusively GM3 (NeuAc) (100%). The fusion of human B lymphocytes with mouse myelomas led to high GM3 (NeuGc) expression (average about 85%) in all mouse/human heterohybridomas examined. Our results indicate the chromosomal gene "transfer" and/or the activation of enzymes involved in NeuGc-biosynthesis due to the somatic cell fusion process, which might explain the mouse dominance in the manifestation of the NeuGc-phenotype in hybridomas of human origin.
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PMID:Expression of gangliosides GM3 (NeuAc) and GM3 (NeuGc) in myelomas and hybridomas of mouse, rat, and human origin. 752 4

Purified GM1 and GM2 gangliosides incorporated into liposomes were injected subcutaneously in BALB/c mice every 3-4 days after pretreatment of the animals with low-dose cyclophosphamide. Serum samples were collected at different intervals and tests by ELISA for the presence of anti-ganglioside antibodies. Four doses (50 micrograms each) were sufficient to raise a measurable primary type of response to GM1, while nine doses were required to obtain measurable IgM antibody titers to GM2. Three monoclonal antibodies (MAbs) wer generated by fusing splenocytes with mouse myeloma cells. The specificity of MAbs was determined by ELISA and HPTLC-immunostaining using a panel of purified glycolipids. The MAb designated E1 showed a high degree of specificity because it reacted only with N-acetyl GM2. Monoclonal antibody A3 reacted predominantly with GM2 and GM1, but also reacted moderately with the GM3 ganglioside. The epitope recognized by this MAb is suggested to be the trisaccharide sequence GalNAc beta 1-4(NeuAc alpha 2-3)Gal. The third MAb (F6) reacted strongly with GM1 but a weak reactivity was also observed with GD1b as well as with asialo-GM1, indicating that the terminal tetrasaccharide Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal- structure is probably involved in antigenic recognition. Formalin-fixed and paraffin-embedded tissue sections were stained with the E1 and A3 MAbs, using the avidin-biotin complex (ABC) technique. Strong immunoreactivity for E1 appeared in the tumor cells of five primary lung carcinomas and in five malignant melanomas. No immunoreactivity was demonstrated in the parenchyma of a lung without malignancy, or in a metastasis from a colon carcinoma.
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PMID:T cell-independent B cell response to self-monosialogangliosides: primary response monoclonal antibodies. 759 Jul 82


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