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)

Administration of high-dose chemotherapy to patients with myeloma, followed by rescue with autologous bone marrow transplantation (ABMT), sometimes induces complete disease remission but relapse is usual. We have attempted to reduce the risk of relapse by selective in vitro removal of myeloma cells from the autologous graft. A combination of the (gal-galNac)-binding lectin peanut agglutinin (PNA), which binds all plasma cells, and the pan-B monoclonal antibody CD19 was assessed for purging marrow of myeloma cells and their putative precursors using a magnetic bead method. Preliminary experiments performed on peripheral blood mononuclear cells spiked with fluorescent-labeled PNA+ Kirk tumor cells showed that a magnetic bead: target cell ratio of 40:1 resulted in a greater than 3-log reduction in PNA+ cells. This technique was then applied to 17 samples of myeloma bone marrow and to 18 samples of normal bone marrow spiked with PNA+ Kirk cells and CD19+ hairy cell leukemia cells. In each case all detectable plasma cells and CD19+ lymphocytes were effectively removed, and normal hemopoietic progenitor cell recovery was greater than 55%. This purging system deserves further study as a means of reducing relapse rates in myeloma patients treated by a combination of high-dose chemotherapy and ABMT.
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PMID:Peanut agglutinin in combination with CD19 monoclonal antibody has potential as a purging agent in myeloma. 171 5

A monoclonal antibody (Mab 2C6) with strong sperm immobilizing and agglutinating activities was generated by cell fusion between spleen cells from a mouse immunized with human seminal plasma (HSP) and mouse myeloma cells. It also showed a strong inhibitory effect on human sperm-egg interaction. The corresponding antigen was present on the whole surface of ejaculated spermatozoa. In male genital organs, immunostaining with Mab 2C6 was observed in epididymis and seminal vesicle but not in testis. By Western blotting, immunostaining with Mab 2C6 was detected around the 15-25 kDa region under both reducing and non-reducing conditions. The antigen corresponding to Mab 2C6 was susceptible to treatment with periodate or trifluoromethanesulfonic acid. The antigenic activities were slightly increased by treatment with neuraminidase but reduced by further treatment with glycosidases. Enzymatic digestions with pronase and papain also reduced the antigenic activities. The antigen molecules exhibited a strong binding affinity to RCA lectin. These results indicated that Mab 2C6 recognized one of the components which might be secreted from epididymis or seminal vesicle and bind to ejaculated spermatozoa as a sperm coating antigen. The corresponding antigen seems to be a glycoprotein and its carbohydrate moiety has an important role in the conformation of the antigen epitope.
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PMID:Sperm immobilizing and fertilization-blocking monoclonal antibody 2C6 to human seminal plasma antigen and characterization of the antigen epitope corresponding to the monoclonal antibody. 171 55

IgE is highly glycosylated, but the function of the oligosaccharide side chains is largely unknown. The previous discovery of an animal lectin, IgE-binding protein (epsilon BP), affords an opportunity to study potential carbohydrate-dependent effector functions of IgE. epsilon BP is a beta-galactoside-specific lectin with binding affinity for IgE and is now known to be equivalent to carbohydrate-binding protein 35 and the Mac-2 Ag; thus, it may have multiple functions in addition to IgE binding. We have previously shown that rat r epsilon BP recognizes sialidase-treated human myeloma IgE to a much greater extent than the untreated IgE. In contrast, human epsilon BP binds essentially equivalently to a monoclonal murine IgE with or without sialidase pretreatment. To validate a possible role for epsilon BP in the IgE system, we investigated the pattern of recognition of epsilon BP for various polyclonal human IgE samples. We show that polyclonal IgE derived from four individuals with hyper-IgE syndrome or atopic dermatitis recognizes epsilon BP and that there is individual variation in the proportion of IgE recognized by epsilon BP, ranging from greater than 60% for one sample to almost undetectable levels in another. We conclude that epsilon BP does indeed recognize polyclonal IgE and that this recognition is modulated by sialylation of IgE oligosaccharides. Furthermore, there exist different IgE glycoforms, varying in the degree of sialylation, and these are distributed in a distinct manner in different individuals.
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PMID:Heterogeneous IgE glycoforms characterized by differential recognition of an endogenous lectin (IgE-binding protein). 191 4

An antibody-lectin enzyme immunoassay technique which had been developed for the analysis of sugar chains of alpha-fetoprotein (N. Kinoshita et al., Clin. Chim. Acta, 179: 143-152, 1989) was used for analysis of sugar chains of myeloma immunoglobulin G (IgG). The IgG sugar chains of four of nine patients with myeloma were found to be highly reactive to Lens culinaris agglutinin as compared with those of six normal controls and 177 patients without myeloma. This reflected a high L. culinaris agglutinin/concanavalin A ratio. The IgGs of these patients were found to have highly sialylated, fucosylated, and bisected biantennary sugar chains at Fab portions as judged by the lectin-blotting technique as well as by high-performance liquid chromatography analysis. These results indicate that some of the myeloma IgG proteins undergo unusual glycosylation processes.
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PMID:Glycosylation at the Fab portion of myeloma immunoglobulin G and increased fucosylated biantennary sugar chains: structural analysis by high-performance liquid chromatography and antibody-lectin enzyme immunoassay using Lens culinaris agglutinin. 193 56

We have reported the production of human monoclonal antibodies (mAb), by the fusion of lymph node lymphocytes from a primary carcinoma patient with murine myeloma cells. Seven heterohybridomas showed reactivity with class III antigens, and five hybridomas (1G12, 2D4, 4H5, 5D10 and 3B10) were reactive with class II antigens. One of these human mAbs (1G12) was intensively studied and results are presented here. 1G12 reacted strongly and specifically with five mammary carcinoma cell lines and showed no cross-reactivity with seven normal fibroblast cells. It continuously produced human mAbs (IgM) at a rate of 4.5-12.5 micrograms/ml over a period of 2 years. Human mAb 1G12 (IgM) was purified by either a combination of anion-exchange chromatography (ABx) and gel filtration (Superose 6) or affinity chromatography (agarose). Immunohistological analysis of frozen tissue sections was performed with biotinylated 1G12. All mammary carcinomas analysed (n = 26) were positive, while the connective tissue of 36 different patients was completely negative with 1G12. In normal breast, endometrium and intestine only a weak or moderate staining of the epithelial cells was observed. Normal oesophagus, small bowel, cervix, uterus, lung and skin were completely negative. Partly purified tumour antigen recognized by 1G12 had a molecular mass of 1-2 MDa and showed strong binding with Ulex europaeus lectin I and Bauhina purpurea agglutinin, indicative for the glucoprotein nature of antigens. These results show that human mAb 1G12 may be useful for the analysis of tumour-associated antigen of mammary carcinoma patients. In further studies the therapeutic and diagnostic application of 1G12 should be analysed in more detail.
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PMID:Tumour-associated antigens of mammary carcinomas recognized by human monoclonal antibody 1G12. 206 59

To examine the nature of the factors influencing the galactosylation pattern of the heavy chain of murine immunoglobulin G (IgG), cell fusion was performed between a myeloma (P3x63Ag8) and a hybridoma (Sp2HL/Bu) cell line which secrete different IgGs possessing structurally distinct CH2-linked oligosaccharide moieties. The glycosylation patterns of the IgGs of the parental and fused cells were studied. Pronase digestion of the purified heavy chains and subsequent end labeling with fluorescein isothiocyanate produced fluoresceinated glycopeptides which were detected and purified by polyacrylamide gel electrophoresis. Structural information was obtained by enzymatic digestion, lectin affinity chromatography, and methylation analysis. IgGs from both parental lines possessed oligosaccharide units displaying microheterogeneity based upon a common symmetrical biantennary structure terminating in beta-GlcNAc. The structures of both IgGs, however, differed in the pattern of the mono- and digalactosylated components. Clones, selected following the fusion of the parental cells, were expanded; and the individual IgGs were purified. All clones produced homodimeric IgG1 and IgG2b as well as heterodimeric IgG possessing both the gamma 1 and gamma 2b heavy chains. Analysis of the carbohydrate moieties of the gamma 1 chain from the homodimeric and heterodimeric IgGs and of the gamma 2b chain from the heterodimeric molecule demonstrates that the polypeptide structure of the heavy chain influences the terminal galactosylation of the glycan unit at the conserved site of glycosylation of IgGs.
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PMID:The polypeptide of immunoglobulin G influences its galactosylation in vivo. 210 49

The activity of N-acetylglucosaminyltransferase (GnT) III, IV and V on a myeloma cell line, OPM-1, was examined after incubation with interleukin 6 (IL-6). While augmenting cell proliferation, IL-6 resulted in a decrease of GnT III activity and an increase of GnT IV and V activities. Consistent with this, OPM-1 cultured with IL-6 showed an increased affinity to Datura stramonium lectin, which recognizes asialo-tri- and asialo-tetraantenary N-linked oligosaccharides. These results indicate that IL-6 modulates glycosyltransferase activity and the oligosaccharide structure of target cells.
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PMID:Modulation of N-acetylglucosaminyltransferase III, IV and V activities and alteration of the surface oligosaccharide structure of a myeloma cell line by interleukin 6. 214 3

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 galactosyltransferase-rich subcellular fraction and wheat germ agglutinin(WGA)-binding microsomal proteins from rat myeloma cells have been used to immunize BALB/c mice. Fusion of the corresponding spleen cells with the Sp2/0 mouse myeloma has lead to the production of hybridomas secreting monoclonal antibodies directed against four proteins of the Golgi complex (GC) and other smooth membranes (SM). Subcellular fractionation of myeloma cells and rat liver, Triton X-114 partitioning, protease treatment and lectin binding studies have permitted us to identify--by immunoblotting--the molecular weight of the proteins involved, their topology and their mode of association with membranes. Morphological analysis has been performed by immunocytochemistry at the light and electron microscopic level. Judging by these criteria, the GCII antigen is a protein of 44 kDa which is loosely associated with the endodomain of Golgi cisternae. GCIII is a detergent-binding glycoprotein of 130 kDa whose epitope is on the endodomain of Golgi cisternae. SMI is a detergent-binding glycoprotein of 58 to 90 kDa found at several stations along the endocytic path: in coated pits, coated vesicles, endocytic vesicles, but not in lysosomes. The epitope recognized by the corresponding antibody faces the ectodomain. When this antibody is added to living cells in culture, it is rapidly internalized. SMII is a detergent-binding glycoprotein of 140 kDa. The epitope recognized is restricted to membranes of Golgi complex cisternae and multivesicular bodies. These reagents should be useful for dissection and perturbation of vesicular traffic.
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PMID:Monoclonal antibodies as markers of the endocytic and secretory pathways. 244 92

Renal disease is a common cause of morbidity and mortality in patients with plasma cell dyscrasia (PCD). We have conducted a systematic study of the formalin-fixed, paraffin-embedded renal tissues from 53 patients with plasma cell dyscrasia, 24 of whom had Bence Jones cast nephropathy (with large casts, often associated with giant cells and polymorphonuclear leukocytes). A battery of 5 immunocytochemical and lectin markers for various segments of the nephron was used [Tetragonolobus lotus, Arachis hypogaea (AH), Tamm-Horsfall protein (THP), epithelial membrane antigen (EMA), and cytokeratin (AE1/AE3)]. In particular, we sought to determine the nature of the intratubular multinucleated giant cells in Bence Jones myeloma cast nephropathy with a variety of epithelial and hematopoietic cell markers. Although tubular epithelial cells stain with their respective markers (whether inflamed, thinned, detached, or adjacent to and lining casts), true intratubular giant cells in PCD were never positive for these tubular markers. In approximately one-third of the cases studied, intratubular and extratubular giant cells stained for several of the seven hematopoietic cell markers employed [i.e., alpha 1-antitrypsin (A1AT), alpha 1-antichymotrypsin (A1ACT), vimentin, and lysozyme], suggesting that giant cells are of hematopoietic origin. The majority of the casts are present in the distal nephron, although some casts were noted in more proximal sites of the nephron. Some larger casts did not stain for THP; smaller casts often showed lamination or stratification of THP staining. Finally, in one-half of the cases, Tamm Horsfall protein (THP) and other distal tubular markers (AH, EMA, AE1/AE3) were found in Bowman's space, almost always in association with interstitial deposits of THP; these markers were virtually never noted in Bowman's spaces of PCD patients without numerous large casts. This suggests that there are communications between distal and proximal nephron, most likely by intraluminal reflux but possibly also through breaks in the tubules and via the interstitium.
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PMID:Myeloma cast nephropathy: immunohistochemical and lectin studies. 246 87


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