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)

The availability of safe and effective preparations of human immune globulin that can be administered intravenously has revolutionized replacement therapy for patients suffering from hypogammaglobulinaemia. Of equal importance and greater interest, however, has been the recognition that super physiological doses of IgG can manipulate an abnormal immune system. Future prospects for the use of immunoglobulin preparations to supply specific antibodies includes the standardization of procedures, whereby patients with acute sepsis may receive antibiotics and immunoglobulin simultaneously. Already there is in vitro evidence that suggests that opsonized bacteria are more readily affected by aminoglycosides. It seems certain that gamma globulin will be used routinely in the management of patients with a number of immunomalignancies, such as chronic lymphatic leukaemia and multiple myeloma that feature hypogammaglobulinaemia, especially when chemotherapy is being administered. Control trials are underway to determine whether gamma globulin given intravenously to premature babies will satisfactorily correct their immuno-deficient state and improve their chances of survival. The immunomanipulative capacity of immunoglobulin is yet to be fully realized. Success in ideopathic thrombocytopenic purpura had led to a trial of gamma globulin in a number of autoimmune conditions. Success has been reported in myasthenia gravis, rheumatoid arthritis, diabetes, patients with circulating antibodies to factor VIII and Kawasaki's disease. The mechanism of action is unknown but almost certainly multifactorial. Two proven mechanisms that will be added to in the future, include blockade of the Fc receptors on cells of the reticulo-endothelial system and manipulation of immunoregulatory T cells by the presence of anti-idiotypic antibodies in the preparation.
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PMID:The clinical use of intravenous gammaglobulin. 244 Jul 43

The response to a single intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP, desmopressin) was studied in two patients with acquired von Willebrand syndrome associated with IgG-kappa myeloma. Following infusion of DDAVP (0.3-0.4 micrograms/kg), prolonged bleeding time was normalized; plasma ristocetin cofactor activity, von Willebrand factor antigen, and factor VIII activity were remarkably increased; and high-molecular-weight forms of von Willebrand factor were demonstrated by crossed immunoelectrophoresis in both patients. Excellent hemostasis was achieved following administration of DDAVP in one patient when it was used for the treatment of gum bleeding and for the prophylaxis of bleeding during and after dental extractions. These observations suggest that DDAVP is an effective alternative to blood products for at least some patients with acquired von Willebrand syndrome in addition to patients with inherited von Willebrand disease, hemophilia A, and uremia.
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PMID:DDAVP in acquired von Willebrand syndrome associated with multiple myeloma. 308 86

A patient with acquired von Willebrand disease associated with multiple myeloma (IgG-lambda) is described. Mixture of his plasma or IgG fraction with washed control platelets resulted in the inhibition of aggregation with ristocetin, but mixture of control plasma or IgG fraction with washed patient platelets showed no inhibition of ristocetin-induced aggregation. Although his vWF: Ag, RCo, and factor VIII coagulant activity were all normal, inactivation of RCo was induced in normal plasma by incubation with patient plasma. Crossed immunoelectrophoretic analysis showed that vWF:Ag was composed of much more anodic component. A marked increase of Factor VIII and a rapid return of RCo to the baseline after 1-deamino-8-arginine vasopressin (DDAVP) infusion were observed. A transient increase in vWF:Ag after the infusion of DDAVP showed with less anodic forms and in the relative proportion as in normal. Treatment of the underlying disease also led to a correction of the bleeding time, improvement of platelet adhesion and ristocetin-induced aggregation, and normalization of crossed immunoelectrophoresis of vWF:Ag. The present study showed that myeloma-associated IgG interacted specifically with the antigenic sites on the von Willebrand portion of the Factor VIII complex.
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PMID:Acquired von Willebrand disease due to inhibitor of human myeloma protein specific for von Willebrand factor. 310 70

A monoclonal antibody (Mab) named EDU-3, was produced by fusing splenocytes from one Balb/c mouse, immunized with a mixture of platelets and non-T cells from heparinized human peripheral blood, with the HAT-sensitive myeloma line P3-NS1/1.Ag4.1. By indirect immunofluorescence (IF) it was seen that this Mab reacted with all normal human platelets and bone marrow megakaryocytes, but did not react with lymphoid cells from normal donors, or platelets from Glanzmann's thrombasthenia (GT) patients. Immunoprecipitation and SDS-PAGE experiments demonstrated that this Mab recognized an epitope on the IIb-IIIa glycoprotein complex (GPC). EDU-3 inhibited platelet aggregation and release of ATP induced by ADP and epinephrine. Aggregation induced by arachidonic acid, ristocetin and bovine factor VIII were not inhibited by EDU-3. The difference between EDU-3 and other Mab directed against the IIb-IIIa GPC is discussed.
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PMID:An antiplatelet monoclonal antibody that inhibits ADP and epinephrine-induced aggregation. 623 32

VIII:C was purified from intermediate-purity concentrate by adsorption on polyelectrolyte E5 and affinity chromatography on Sepharose/anti-VIIIR:Ag. The highly purified VIII:C preparation (sp. act. 1598 U/mg) was used to immunize Balb-C mice. Spleen cells from a mouse with a serum antibody titer of 963 U/ml were fused with P3 NSI mouse myeloma cells. Hybrid clones were screened by a coagulation inhibition assay and by a four-layer antibody adsorption procedure. Nine monoclonal antibodies specific to VIII:C were produced. Five of these antibodies have been cloned and grown in mouse ascitic fluid. Antibody titers from ascitic fluid ranged from 35 to 82,000 BU/ml. The antibodies, when radiolabeled, form a high-molecular-weight complex with antigens present in normal plasma and factor VIII concentrate, but not when incubated with CRM-negative hemophilic plasma. A two-site assay using a combination of monoclonal antibodies is able to detect VIII:CAg in normal plasma and in factor VIII concentrate. Sensitive two-site immunoradiometric assays using monoclonal antibodies as the solid phase have been set up.
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PMID:Monoclonal antibodies to human procoagulant factor VIII. 640 38

We have studied four patients suffering from acquired von Willebrand's disease. All patients had a severe bleeding diathesis with recurrent life-threatening haemorrhages. Three of the patients had a monoclonal gammopathy and one of these developed multiple myeloma. In three patients tested, a plasma inhibitor to ristocetin cofactor activity was detected. In each case this was localized to the IgG fraction of plasma. In addition, VIII:C activity was found to be associated with the IgG fraction of patients' plasma and altered mobility of VIII:C was detected on Laurell immunoelectrophoresis. Furthermore, plasma from all four patients and the IgG fraction therefrom resulted in a dissociation of normal VIII:C into two components separable by gel-filtration on Sepharose 6B. Finally the circulating half-life of the three factor VIII activities was found to be markedly reduced in the patients with acquired von Willebrand's disease. We conclude that in the patients studied the coagulation defect was related to the presence of a circulating inhibitor to the factor VIII complex and that this inhibitor was associated with the IgG fraction of plasma.
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PMID:Acquired von Willebrand's disease: demonstration of a circulating inhibitor to the factor VIII complex in four cases. 640 78

Acquired von Willebrand syndrome is reported in four patients with monoclonal IgG: benign gammapathy in three cases, multiple myeloma in one case; to our knowledge, this last association has not been previously reported. Coagulation abnormalities included a borderline bleeding time, a low platelet retention on glass beads, decreased levels of factor VIII coagulant activity (VIII: C), factor VIII related-antigen (VIII R: Ag) and ristocetin induced agglutination cofactor (VIII R: RC). The late clinical onset, the negative family history and the immunological abnormality suggest an acquired von Willebrand syndrome. After cryoprecipitate infusion the patients did not show the expected rise and there was no secondary increment in factor VIII: C. Time-dependent inhibition of factor VIII R: RC and factor VIII: C was found in one case only and was associated with qualitative abnormality of factor VIII R: Ag demonstrated by crossed-immunoelectrophoresis. It was not possible to interpret this last test in the other cases, due to the very low level of factor VIII R: Ag. The factor VIII abnormalities might be related to the binding and/or destruction of factor VIII by a circulating antibody, or to the adsorption of this factor on the malignant lymphocytes.
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PMID:[4 cases of acquired Willebrand factor deficiency associated with monoclonal dysglobulinemia]. 642 Dec 19

Spleen cells of a BALB/c mouse immunized with factor VIII procoagulant activity (VIII:C) (isolated by affinity chromatography) were fused with mouse myeloma cells (P3 x 63 Ag8). After the fusion 12/32 wells produced an inhibitor to VIII:C. Cells from one well (1B3) were subcloned four times in order to isolate the hybridoma that produces the anti-VIII:C antibody. Injection of hybridoma cells in pristane pretreated BALB/c mice results in anti-VIII:C titers of 5000-10,000 Bethesda U/ml. Analysis of the produced immunoglobulin demonstrated heavy chains of IgG1 (produced by the myeloma cell line) and IgG2b subclass. The 1B3 antibody neutralizes VIII:C in LMW FVIII, crysosupernatant, cryoprecipitate, and normal plasma. It was found that binding of the IgG to FVIII results in a delay in its activation and not in an inhibition of its cofactor activity. The antibody removes VIII:C from pooled normal plasma when coupled to Sepharose; when coupled to plastic tubes, it binds VIIICAG from isolated VIII:C, purified FVIII, and pooled normal plasma; it does not bind VIIIR:AG, fibrogen, or serum VIIICAG. The 1B3 antibody can be used successfully in an IRMA for VIIICAG.
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PMID:A monoclonal antibody to VIII:C produced by a mouse hybridoma. 679 73

Partially purified preparations of porcine factor VIII:C were used to immunize mice and spleen cells from the immunized animals were fused to NS-1 mouse myeloma cells. The ability of hybrid culture fluids to bind factor VIII:C was detected with a radiolabelled, affinity-purified, human antihuman VIII:C inhibitor. Three cloned hybrid lines have been obtained that preferentially bind to VIII:C when compared to von Willebrand factor binding. Two of these monoclonal antibodies partially inhibit VIII:C coagulant activity. The third antibody does not inhibit VIII:C, but it can be used as an affinity reagent to absorb dissociated VIII:C out of solution. Active coagulant can be recovered by elution in 50% ethylene glycol. The VIII:C obtained has a specific activity of 6 units/micrograms based on absorbance measurements. When analyzed on SDS gels, the unactivated VIII:C contains 3 bands of apparent molecular weight 166,000, 130,000 and 76,000. Thrombin treatment results in a 40 fold increase in activity and cleavage to products of 76,000, 67,000 an 50,000 and small amounts of lower molecular weight peptides. EDTA inactivation of the factor VIII:C results in the separation of the 166,000 and 130,000 chains from the 76,000 chain, suggesting a Ca++ dependent noncovalent interaction among the chains.
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PMID:Monoclonal antibodies to porcine factor VIII coagulant and their use in the isolation of active coagulant protein. 680 Apr 19

The behaviour of the factor VIII/von Willebrand factor complex (VIII:C, VIIIR:Ag and VIIIR:RCof) was investigated in 23 patients with secretory myeloma, in 2 patients with non-secretory myeloma and in 5 patients with macroglobulinemia. In most patients (21 of 25 patients with plasma cell myeloma and 2 of 5 patients with macroglobulinemia) VIIIR:Ag was increased usually without corresponding increases in VIII:C and VIIIR:RCof. There was no correlation between the VIIIR:Ag levels and paraprotein Ig type or level nor with the presence or the absence of Bence Jones proteins in serum and urine. Furthermore, increased levels of VIIIR:Ag were found in patients with non-secretory myeloma. In general, VIIIR:Ag was higher in patients with extensive bone lesions and there was a significant correlation between cell mass and the VIIIR:Ag level. The crossed-immunoelectrophoresis of plasmas with discrepant VIIIR:Ag and VIIIR:RCof showed variation from the normal pattern.
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PMID:Factor VIII complex in myelomatosis and related disorders. 681 70


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