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)

Fourteen patients with severe viral illnesses were given intravenous infusions of a modified interferon inducer, polyriboinosinic-polyribocytidylic acid-poly-L-lysine complexed with carboxymethylcellulose [poly)I:C.LC)], during a phase 1 clinical trial. The first eight patients received 0.15 to 0.30 mg of poly(I:C.LC) per kg of body weight daily for 5 consecutive days, and another received two courses separated by 1 week. A second group of five patients was given single intravenous infusions of 0.10 to 0.15 mg of poly(I:C.LC) per kg. Interferon was detectable in the serum 8 to 16 h after injection. Titers ranged from 15 to 800 U/ml and varied directly with the dose of poly(I:C.LC). Interferonemias persisted for 12 to 48 h. In patients receiving 5-day courses of poly(I:C.LC), lower levels of serum interferon (0 to 160 U/ml) occurred on days 2 through 5, characteristic of a hyporesponsive state. An exception was a 69-year-old patient with disseminated varicella zoster, multiple myeloma, and renal insufficiency whose serum contained 3,150 U of interferon per ml on day 3 of 0.3 mg of poly(I:C.LC) per kg. Fever (39 to 40.5 degrees C, rectally; 13 of the 14 patients) peaked 3 to 8 h after completion of infusions. Other toxic effects included lymphopenia (10 of the 14 patients), hypotensive episodes (7 of the 14 patients), and minor elevations of serum glutamicoxalacetic transaminase and lactic dehydrogenase.
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PMID:Modified polyriboinosinic-polyribocytidylic acid complex: sustained interferonemia and its physiological associates in humans. 50 Jan 89

Twenty-two patients (16 male, six female; median age 34 years, range 16-49) with acute myeloid leukemia (1st complete remission (CR), n = 9), acute lymphocytic leukemia (1st CR, n = 5), chronic myeloid leukemia (chronic phase n = 5, accelerated phase n = 1), malignant lymphoma (n = 1) and myeloma (n = 1) were transplanted with unmanipulated donor bone marrow after standard conditioning including the monoclonal antibody Campath-1G daily from day -4 to day 0. No further graft-versus-host disease (GVHD) prophylaxis was given. All patients engrafted and neither graft failure nor rejection were observed. Acute GVHD grade I (skin) was seen in 12 out of 21 patients at risk. Acute GVHD grade II (skin) occurred in two patients. Severe GVHD (grade III, IV) of the gut, liver and skin developed in two patients. The overall incidence of severe acute GVHD (II-IV) was 19% of the patients at risk. Chronic GVHD (skin only) was seen in eight patients (42%) (six of extensive severity). A total of 14 patients died, the causes being relapse (four), direct cytotoxic drug toxicity (one), a GVHD (two), disseminated varicella zoster (one), systemic tuberculosis (one), interstitial pneumonitis (three) and veno-occlusive disease (two). These results indicate that the intravenous administration of Campath-1G may have reduced the incidence of severe acute GVHD without the occurrence of graft failure. However, the incidence of chronic GVHD does not appear to have decreased.
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PMID:In vivo use of Campath-1G to prevent graft-versus-host disease and graft rejection after bone marrow transplantation. 160 Apr 13

Hybridomas producing human monoclonal antibodies (HMAbs) against varicella-zoster virus (VZV) were generated by fusing murine myeloma cells with human lymphocytes immunized in vitro. An assay system was developed to select anti-glycoprotein (gp)III HMAbs from the pool of anti-VZV HMAbs. A murine anti-gpIII MAb, 4B7, did not react with a VZV-infected cell homogenate, but did react with a VZV-infected cell monolayer, whereas anti-gpI and anti-gpII MAbs reacted with both antigens. Hybridomas were screened to obtain HMAbs having a reaction profile similar to that of 4B7 and one such clone, V3, stably produces human IgG1 (kappa). HMAb V3 immunoprecipitated a VZV antigen of 115K to 120K, which was not immunoabsorbed by an anti-gpII HMAb, implying that V3 recognizes gpIII. V3 neutralized VZV independently of complement, unlike anti-gpI and anti-gpII HMAbs. All five strains of VZV tested were completely neutralized by V3, and the dose of V3 required to reduce the number of virus plaques by 50% ranged from 0.027 to 0.15 micrograms/ml. V3 was also able to inhibit the spread of virus infection from infected to uninfected cells, whereas anti-gpI and anti-gpII HMAbs could not. In addition, V3 mediated antibody-dependent cellular cytotoxicity but not complement-dependent cytotoxicity of VZV-infected cells. The results suggest that an anti-gpIII HMAb may provide a new means of passive immunoprophylaxis and also help to identify an antigenic epitope appropriate for a subunit vaccine.
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PMID:A human monoclonal antibody against varicella-zoster virus glycoprotein III. 165 71

Failure of host defense systems associated with malignancies may be attributable to the tumor, to cytoreductive therapy or to combined endogenous and iatrogenic influences. Management of the resulting increased susceptibility to infections may require supplementation of antibiotic therapy with additional forms of treatment, including passive immunization with antibodies. This review discusses the use of immunoglobulin preparations for intravenous administration (IVIG) in patients with secondary immunodeficiencies associated with neoplasia. A suitable model for evaluating the prophylactic effect of IVIG is chronic lymphocytic leukemia. Many observations suggest that IVIG reduces the frequency of acute respiratory infections. Another malignant condition with decreased serum levels of polyclonal immunoglobulins and high frequency of infections is multiple myeloma. A crossover study recently demonstrated that IVIG significantly (P less than 0.01) reduced the frequency of respiratory tract infections in these patients. Furthermore the prophylactic effect of IVIG was evaluated in patients with small cell carcinoma of the lung. In a randomized prospective trial it was noticed that IVIG applied during intensive chemotherapy and irradiation courses significantly (P = 0.04) reduced the frequency of infections. Evidence for a therapeutic effect of IVIG was obtained in adult tumor patients and in children with leukemia or non-Hodgkin's lymphoma who developed severe varicella-zoster virus infections. The treatment effectively controlled fever, skin lesions and neuralgia and prevented progression of the infection. Therapeutic usefulness of IVIG in bacterial infections is still based on anecdotal evidence. Experimental data suggest that in addition to effects mediated by specific antibodies, nonspecific interactions of IgG molecules with Fc-receptors on macrophages may be clinically important.
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PMID:Prophylactic and therapeutic use of immunoglobulin for intravenous administration in patients with secondary immunodeficiencies associated with malignancies. 284 Jun 30

Hybridomas producing human monoclonal antibodies (mAb) against varicella-zoster virus (VZV) were generated by fusing human splenic lymphocytes with mouse myeloma cells. Before cell fusion, lymphocytes were stimulated in vitro with viral antigens and pokeweed mitogen. This combination synergistically increased the generation of VZV-specific hybridomas. Five established hybridomas have been stably producing mAb for at least 9 months. These mAb, designated V1, V2, V6, V8 and V9, were of the IgG1, lambda isotype. They bound to all 6 tested VZV strains but not to other herpes viruses, with the exception that V1 bound to herpes simplex virus (HSV) as well as VZV. Immunoprecipitation analysis showed that V1, V6 and V9 recognized glycoprotein gpII, whereas V2 and V8 recognized gpI. In addition, V1 reacted with the gB glycoprotein of HSV. All these mAb neutralized viral infectivity. The neutralizations by V2 and V8 were more effective and more complement dependent than those by V1, V6 and V9. Immunofluorescence tests revealed that all these mAb bound to the surface membrane of VZV-infected cells. These results suggest that cell fusion between in vitro stimulated lymphocytes and mouse myeloma cells is a reliable method for the generation of hybridomas capable of stable production of human mAb. The human mAb thus developed may provide a new means of passive immunization of humans against VZV infection.
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PMID:Hybridomas producing human monoclonal antibodies against varicella-zoster virus. 303 47

Nine hybrid cell lines producing antibodies specific for cytomegalovirus (CMV) antigen were obtained after fusion of P3/X63-Ag8 myeloma cells with spleen cells from BALB/c mice immunized with CMV complement-fixing antigen. By the immunoblot technique, five of nine antibodies (4D11, 7B4, 7D2, 8E3, and 8E10) were identified as being reactive to a CMV glycosylated polypeptide with molecular weight of 66,000 (GP66). Four other antibodies (1B8, 8E9, 4D2, and 7E2) appeared to be reactive with CMV antigen(s) only if the antigen was not denatured by sodium dodecyl sulfate. These remain unassigned until further studies are done. With the enzyme-linked immunosorbent assay (ELISA), competitive bindings were performed with a constant amount of horseradish peroxidase-conjugated antibody and various concentrations of unconjugated homologous and heterologous antibodies on CMV antigen-coated ELISA wells, and the antigenic determinant specific for each antibody was determined. The nine antibodies could be classified into six different groups, each group reacting with a different epitope or a different region with two or more antigenic determinants which are so close to each other that they cause binding inhibition. They are groups A (4D11), B (7B4, 8E10), C (7D2), D (4D2, 7E2, 8E9), E (8E3), and F (1B8). The extent of competition among antibodies within each group was the same. By using the two antibodies that reacted with different epitopes on GP66, a double-antibody sandwich ELISA method was developed. The method was sensitive enough to detect as little as 50% of the antigen present in one infected cell or 0.000245 U of CMV complement-fixing antigen per test well. Other strains of CMV (David, Kerr, Espilat, C-87, and five clinical isolates) gave positive results, whereas herpes simplex virus types 1 and 2, varicella-zoster virus and Epstein-Barr virus nuclear antigen preparations did not. By the indirect immunofluorescence assay, antibodies 4D11 and 8E3 were able to detect GP66 in the nucleus of CMV-infected F-5000 human embryonic fibroblasts as early as 2 h postinfection and were superior in this respect to the remaining seven antibodies tested. By the double-antibody sandwich ELISA, the presence of GP66 in CMV-infected cells was detected as early as 2 h postinfection.
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PMID:Production and characterization of monoclonal antibodies specific for a glycosylated polypeptide of human cytomegalovirus. 619 74

Investigation of recurrent venous thromboembolic events in a 46-year-old man with progressive IgG kappa (total serum IgG, 74.3 mg/ml) multiple myeloma revealed profound reductions in free protein S (PS) antigen (<0.l U/ml) and PS activity (0.33 U/ml). Total PS antigen, protein C, antithrombin III, and C4b-binding protein levels were within normal limits. The patient had no family history suggestive of a congenital PS deficiency and no history of thrombosis predating the diagnosis of his plasma cell dyscrasia. Patient IgG was isolated from serum using a protein A-sepharose affinity column and characterized. PS-dependent clotting assays (Staclot Protein S, Diagnostica Stago, Asnieres sur-Seine, France) performed on normal pooled plasma mixed with dilutions of patient IgG (0.0-33.0 mg/ml) revealed a dose-dependent neutralization of PS activity by 43%. Total and free PS antigen levels were measured using Laurell rocket electroimmunodiffusion (Assera-Plate Protein S, Diagnostica Stago), which revealed a similar dose-dependent reduction in free PS antigen but preserved normal total PS antigen. Free PS antigen was reduced by 77% to 0.23 U/ml using an IgG concentration (16.5 mg/ml) less than one-fourth of that of the patient at time of serum collection. Specific binding of the patient IgG to commercially available purified human PS was demonstrated by Western immunoblot analysis. Whereas acquired free PS deficiency has been previously reported in association with nephrotic syndrome, inflammatory bowel disease, HIV infection, and varicella infection, this is the first reported case of a hypercoagulable syndrome associated with acquired free PS deficiency and multiple myeloma.
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PMID:Acquired free protein S deficiency associated with multiple myeloma: a case report. 860 34

Intravenous immunoglobulin (IVIg) are therapeutic preparations of intact IgG that are obtained from a pool of more than one thousand healthy blood donors and contain antibodies directed toward a large panel of microbial agents. IVIg contain high amounts of antibodies with opsonising activity and are indicated in substitutive treatment of patients with constitutive hypogammaglobulinemia. IVIg also contain antibodies able to neutralize certain bacterial toxins exerting superantigenic activity, and by this mechanism exert both anti-infectious and immunomodulating activity. During the last fifteen years, indications of IVIg in the prophylactic treatment of infections have been well defined: a) primary antibody deficiency; b) multiple myeloma and chronic lymphocytic leukemia with hypogammaglobulinemia and recurrent bacterial infections; c) bone marrow allograft; d) childhood AIDS; e) chicken pox seroprophylaxis in immunosuppressed patients and pregnant women. Therapeutic indications of IVIg in infectious diseases are limited to chronic parvovirus B19 infection associated or not with HIV infection. Other therapeutic indications are not well defined.
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PMID:[Intravenous immunoglobulins: anti-infection indications]. 1085 66

Disseminated herpes simplex virus (HSV) and varicella zoster virus (VZV) have been reported individually in immunosuppressed adults. We present a case of coinfection with disseminated HSV and VZV infection in a patient taking thalidomide for relapsed multiple myeloma. This is the first report of opportunistic infection associated with thalidomide.
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PMID:Disseminated herpes simplex virus and varicella zoster virus coinfection in a patient taking thalidomide for relapsed multiple myeloma. 1203 17

Varicella-Zoster virus (VZV) immune globulin (VZIG) derived from pooled human serum is currently used in immunotherapy of VZV-associated complications of chickenpox and shingles. We developed a mouse-human chimeric antibody against a VZV glycoprotein E (gE) epitope as a safer replacement for VZIG. Variable (V) heavy- and V kappa light-chain exons, derived from an anti-VZV gE antibody secreting mouse hybridoma cell line, were cloned into expression vectors containing an immunoglobulin promoter and enhancer, and human IgG1 or kappa constant (C) region genes. The expression vectors were cotransfected into mouse myeloma cell line (NSO), generating transformants that secreted chimeric human-mouse IgGs. The chimeric and the parent mouse antibody were indistinguishable in their antigen binding specificity. VZV gE chimeric antibody may prove to be a prophylactic antibody that could provide significant advantages over VZIG in having defined specificity, lessened possibility of contamination with viral pathogens, and consistent availability.
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PMID:A chimeric antibody to varicella-zoster virus glycoprotein e. 1578 9


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