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)

Fc receptor for human IgA was detected on rabbit, sheep and human ORh- red blood cells. This Fc alpha receptor was able to bind human secretory or myeloma IgA, IgA1 or IgA2 and alpha chains. The ligand binding was detected by complement mediated lysis and agglutination with specific anti-IgA serum. Blocking experiments showed the inability of Fab(IgA) fragment or of secretory component to inhibit the IgA binding.
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PMID:Fc receptor for IgA on erythrocytes. 716 22

Growth characteristics of 17D yellow fever virus (17D-YF) and conditions for infection were studied in U937, a macrophage-like, Fc receptor-bearing continuous human cell line. Antibody to 17D-YF was obtained by immunization of normal subjects with 17D-YF vaccine. Cells were infected in the presence or absence of immune whole sera or immunoglobulin fractions. Infection of U937 was temperature dependent; the yield of virus was variable but at low temperature viral titers were consistently higher when infection was established in the presence of antibody. Results of infectious center assays indicated that the increased yield of virus was largely or entirely due to an increase in the number of cells producing virus early in the course of infection. Enhancement of viral growth was mediated by IgG but not IgM fractions of immune sera. Trypsinization of U937 resulted in a 90 to 95% reduction of infection in the absence of antibody but in the presence of antibody viral titers were higher in trypsinized than in nontrypsinized cells. Antibody to 17D-YF, contained in the whole IgG fraction of sera, bound to U937 to mediate infection without first being complexed to virus. Preincubation of U937 with IgG1 but not IgG2 myeloma proteins abrogated antibody-mediated infection. This result is compatible with the known affinities of U937 Fc receptors for specific subclasses of IgG and provides evidence for the role of the Fc receptor in antibody-mediated enhancement of viral growth. Persistent infection characterized by a lack of detectable cytopathogenic effect was established in long-term cultures of U937. This pattern of infection might be related to the unique effectiveness of the 17D-YF vaccine.
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PMID:Growth of 17D yellow fever virus in a macrophage-like cell line, U937: role of Fc and viral receptors in antibody-mediated infection. 725 55

Membrane proteins which selectively bind to the Fc portion of IgG were identified in the Nonidet P-40 extracts of radiolabeled thioglycollate- elicited mouse peritoneal macrophages. Affinity columns of various IgG preparations coupled to Sepharose 4B were used to absorb the Fc-binding proteins. Analysis of the acetic acid or sodium dodecyl sulfate (SDS) eluates from aggregated human IgG or antigen-complexed rabbit IgG columns revealed two Fc(gamma)/-specific proteins with apparent 67,000 and 52,000 mol wt. These proteins were not detected in acid or SDS eluates from F(ab')(2) columns or in eluates from IgG column, over which were passed lysates of Fc receptor-negative cells. With the use of affinity columns that contained aggregated mouse myeloma proteins of different IgG subclasses, we found that the 67,000-dahon protein selectively binds to IgG2a, whereas the 52,000-dalton protein binds to IgG1 and IgG2b. Neither protein was found in SDS eluates from IgG3 columns. Trypsin treatment of the macrophages before detergent lysis removed the 67,000-dalton protein, although it leaves intact the 52,000-dalton protein. These results provide structural confirmation for the existence of separate Fc receptors on mouse macrophages and indicate that the two Fc-binding proteins identified in this study represent all or part of the trypsin- sensitive Fc receptor which binds IgG2a and the trypsin-resistant Fc receptor which binds IgG2b and IgG1.
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PMID:Structural evidence for distinct IgG subclass-specific Fc receptors on mouse peritoneal macrophages. 743 Sep 49

A monoclonal antibody designated Apt4, which is IgG1, was produced by fusion of mouse myeloma cells to spleen cells from a BALB/c mouse immunized with normal human platelets. Apt4 whole IgG caused the aggregation of both platelet rich plasma (PRP) and washed platelets from normal subjects and a patient with Bernard Soulier syndrome but not those from two patients with the Type 1 Glanzmann's thrombasthenia. No aggregation was observed when Apt4 F(ab')2 fragments were used. Immunofluorescence study showed that both whole IgG and F(ab')2 fragments of Apt4 bound to fresh or formalin fixed platelets from normal subjects and a patient with Bernard Soulier syndrome but not to those from two patients with Glanzmann's thrombasthenia. Aggregation induced by Apt4 IgG was inhibited by EDTA (10 mM), PGE1 (1 mM), 2-deoxy-D-glucose/antimycin (1.4 uM), and apyrase (20 units/ml). Preincubation of normal PRP with monoclonal anti-GPIIb/IIIa or anti-GPIb antibodies completely or partially inhibited the Apt4-induced aggregation, whereas anti-GPIIIa antibodies have no effects on this activation. Monoclonal ant-Fc gamma RII antibody (IV.3) inhibited Apt4 induced aggregation. Immunoprecipitation of 125I-labeled platelet membrane lysate by Apt4 IgG showed two protein bands with a molecular weight of 145,000 and 95,000 daltons respectively under non-reducing condition, which are corresponding to GPIIb and GPIIIa. In conclusion, Apt4 antibody binds to GPIIb/IIIa complex and induces aggregation, requiring energy metabolism, calcium, ADP release and Fc portion of IgG to interact with Fc receptor, but independent of thromboxane A2 formation.
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PMID:Mechanism of platelet aggregation induced by a monoclonal antibody requiring Fc portion. 768 51

Mouse macrophage (Mphi) hybridoma clones were generated by somatic cell hybridization of myeloma X63 cells (H-2d) with C57BL/6 (H-2b) peritoneal exudate cells elicited with a streptococcal preparation, OK432, or thioglycollate medium. Although they hardly adhered to plastic dishes and could not be morphologically distinguished from parental X63 tumor cells, the clones retained Mphi characteristics. These included phagocytosis and production of lysozyme and nonspecific esterase, suggesting that they were hybridomas derived from Mphi. Some of them expressed various levels of Ia antigen and Fc receptor. Because they induced proliferation of T cells from Balb/c mice but not those from C57BL/6 mice, the Ia antigen of Mphi hybridoma was assumed to be derived from peritoneal Mphi. The level of proliferation induction was correlated to the level of Ia antigen expression. Several clones produced a factor that cytostatically inhibited growth of murine mammary carcinoma and was serologically identified with arginine deiminase.
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PMID:Development and characterization of macrophage hybridomas derived from murine peritoneal exudate cells. 776 73

Soluble CD16 (sCD16) are soluble part of Fc receptor for IgG which control in mice, proliferation of hybridoma B cells and IgG production. The levels of sCD16 in 165 myeloma patients and 29 patients with MGUS appear significantly different:25a.u./ml versus 144a.u./ml and values of stage I are significantly higher than those of stages II + III.sCD16 might be a prognosis factor in myeloma.
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PMID:[Correlation between the serum level of soluble CD16 and the staging of myeloma: study of 214 serums]. 800 56

Radiolabeled antibodies have shown promise for the treatment of lymphoma and for solid tumor targeting. Campath-1H is a humanized monoclonal antibody that reacts with the CD52 antigen present on human lymphoid and myeloid cells. Campath-1H is a gamma1 (G1) isotype that induces lymphopenia via an Fc-mediated mechanism(s). Isotype switches were engineered, and the resulting antibodies were expressed in NS0 mouse myeloma cells and biosynthetically radiolabeled with [35S]methionine. The forms included G1, G4, and a G4 variant that contained alanine substitutions at (EU numbering) Leu-235, Gly-237, and Glu-318. All isotypes bound antigen equivalently as assessed by target cell binding in vitro. The G4 variant had a greatly reduced capacity to interact with Fc receptor by virtue of reduced binding to THP-1 human myeloid cells and by a 1000-fold increase in EC50 to intermediate antibody-dependent cellular cytotoxicity. The pharmacokinetics of the isotypes were compared in CD-1 (nu/nu) mice bearing an experimental antigen-expressing tumor. The plasma half-life and tumor uptake were increased for the G4 variant. The G4 variant showed significantly less spleen, liver, and bone uptake but similar uptake in the lung, kidney, and stomach and lower tissue-to-blood ratios. Immunogenicity was assessed after repeated monthly administrations of unlabeled antibody in BALB/c mice. A 50% reduction in the incidence of anti-globulin response was observed for the G4 variant. These properties suggest that antibodies with reduced Fc receptor interaction merit additional study as potential targeting vehicles relative to other isotypes for radioimmunotherapy or situations where diminished normal tissue binding contributes to efficacy.
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PMID:Improved biodistribution, tumor targeting, and reduced immunogenicity in mice with a gamma 4 variant of Campath-1H. 861 27

Stimulation of the CD40 antigen on normal B cells by crosslinking of anti-CD40 mAbs via their Fc receptor using a Fc gamma RII(CD32)-transfected mouse fibroblast cell line ('CD40 system') results in activation and proliferation. Not only normal B cells, but also malignant B cells fitting in the low-grade malignancy category such as chronic lymphocytic leukemia (CLL), hairy cell leukemia and follicular lymphoma could be induced to proliferation upon CD40 stimulation. Here, the 'CD40 system' has also been used to culture intermediate and high grade malignancies. Proliferation was measured by 3H-thymidine incorporation and cell counting after culture. Time curves showed that at day 7 most cultures were optimal. By flow cytometry, morphology and assessment of light chain restriction the monoclonal nature of the cultured B cells was proven. We confirmed that B cell malignancies with a more slowly evolving course, such as CLL (n=11), PLL (n=5), and low-grade NHL (immunocytoma and follicular cb/cc n=9), could successfully be cultured in the 'CD40 system'. In contrast, four out of seven cases of mantle cell lymphoma did not proliferate. Cases of precursor B lineage ALL (n=7), high grade NHL (n=3) and multiple myeloma (n=10) showed a heterogenous growth pattern. We conclude that the 'CD40 system', although not always successful, is a useful tool to culture a whole variety of B cell malignancies.
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PMID:Proliferation of B cell malignancies in all stages of differentiation upon stimulation in the 'CD40 system'. 864 67

An increasing amount of literature has been published concerning the interaction of the CD40 antigen and its ligand with regard to normal B cell ontogeny. In this review, an overview of the CD40 antigen and the CD40 ligand is given, focussing on their possible role in B cell malignancies. Data on the expression of the CD40 antigen on various B cell malignancies (acute and chronic leukemias, non-Hodgkin's lymphoma and multiple myeloma) are presented. The recently developed novel culture "CD40 system" is described. This system is a powerful tool used to culture normal B cells, but also most malignant B cells. We demonstrate in addition a more prominent role of the human Fc receptor presenting murine fibroblasts in the "CD40 system", especially in relation to cultured plasma cells. Finally, some important applications of the "CD40 system" are also summarized.
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PMID:The role of the CD40 antigen on malignant B cells. 881 71

Cross-linking of surface immunoglobulin (sIg) has been shown to induce either activation or apoptosis of mature B cells presumably depending on the nature of antigens. However, the nature of antigens for induction of mature B-cell apoptosis is not yet fully understood. We cross-linked sIg of mature B cells with various amounts of either anti-Ig antibodies in the soluble form or anti-Ig coupled to erythrocytes or myeloma cells as surrogate membrane-bound antigens. Anti-Ig antibodies coupled to cell surface membrane induced rapid and extensive apoptosis of normal spleen B cells even in the absence of signalling via the Fc receptor. In contrast, soluble anti-Ig induced proliferation or apoptosis of mature B cells depending on the concentration of anti-Ig. The extent of apoptosis induced by soluble anti-Ig was limited compared to that induced by membrane-bound anti-Ig. These results suggest that mature B cells undergo apoptosis or proliferation depending on whether antigens are soluble or membrane-bound and on antigen doses.
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PMID:Antigen receptor cross-linking by anti-immunoglobulin antibodies coupled to cell surface membrane induces rapid apoptosis of normal spleen B cells. 965 21


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