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)

Infection of mouse myeloma cells (MPC-11) with vesicular stomatitis (VS) virus resulted in rapid and marked reduction in cellular RNA synthesis considerably before cell viability was compromised. Mouse myeloma cells responded maximally to viral infection at a multiplicity of 1 and were considerably more se;sitive to shut-off of RNA synthesis than were mouse L cells or BHK-21 cells. This inhibition of cellular RNA synthesis was shown not to be caused by differential membrane permeability of infected and uninfected MPC-11 cells to [3H]uridine, nor was it due to greater degradation of previously synthesized RNA. VS viral infection appeared not to impede transport of newly synthesized nuclear RNA to the cytoplasm; moreover, infected cells accumulated polyadenylated mRNA at the same rate as did uninfected cells. Polyacrylamide gel electrophoresis of newly synthesized nuclear RNA demonstrated that the polydisperse nature and size distribution were not affected by VS viral infection. Isolated nuclei of infected MPC-11 cells also inhibited greatly impaired capacity to synthesize RNA despite the absence of cytoplasmic factors. Infected-cell cytosol did not inhibit transcription by uninfected-cell nuclei, nor did uninfected-cell cytosol reverse viral inhibition of nuclear transcription. Studies with alpha-amanitin revealed that VS viral infection inhibited the activity of polymerases I, II, and III, but only polymerase II was affected progressively throughout infection and to a much greater extent. These data suggest that, even at low multiplicities of infection, VS virus rapidly shuts off cellular RNA synthesis at the level of nuclear transcription.
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PMID:Inhibition of RNA synthesis in mouse myeloma cells infected with vesicular stomatitis virus. 20 71

Infection of mouse myeloma (MPC-11) cells with vesicular stomatitis virus resulted in rapid loss in activity of cellular RNA polymerases associated with nuclear chromatin. No RNA polymerase inhibitor could be detected in extracts of infected cell nuclei. Reconstitution experiments with solubilized RNA polymerases dissociated from chromatin of infected and uninfected cells demonstrated that vesicular stomatitis viral infection did not affect the ability of the polymerases to function on endogenous or exogenous templates; nor did infection alter the template capability of the chromatin. Measurement of the number of actively growing RNA chains revealed that infected cell nuclei contained fewer active polymerase units; however, the rates of RNA chain elongation were the same in nuclei from infected and uninfected cells. Quantitation of the number of polymerase units active in nuclear chromatin revealed that the alpha-amantin-sensitive polymerase II was more severely reduced by viral infection than were polymerases I and III.
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PMID:Vesicular stomatitis virus infection reduces the number of active DNA-dependent RNA polymerases in myeloma cells. 22 70

Aleutian disease of mink is a viral illness characterized by systemic plasmocytosis and hypergammaglobulinemia. Some affected mink develop a monoclonal gammaglobulin spike and Bence-Jones proteinuria. A case of multiple myeloma in a mink handler with a 15-year history of exposure to Aleutian mink is presented. Previously reported cases of possible Aleutian disease (AD) in man are discussed and the pathogenesis of AD reviewed. Aleutian disease virus (ADV) may produce asymptomatic infection in exposed individuals. Available data suggest symptomatic disease in humans is extremely rare.
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PMID:Multiple myeloma in a mink handler following exposure to Aleutian disease. 22 31

Somatic cell hybrids (hybridomas) between mouse myeloma cells and spleen cells derived from BALB/c mice immunized with inactivated rabies vaccine were found to produce antibodies to rabies virus. Monoclonal antibodies with different specificities were obtained either from the mass culture directly after fusion or from clones derived from a single-cell cloning procedure. Several strains of fixed or street rabies virus were analyzed by virus neutralization procedures which demonstrated differences in their antigenic composition. Hybridoma antibodies were able to protect experimental animals from lethal rabies virus infection.
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PMID:Monoclonal antibodies against rabies virus produced by somatic cell hybridization: detection of antigenic variants. 27 9

Infusion of cycloheximide i.v., an antibiotic known to inhibit synthesis of protein, at a rate of 0.2 mg/kg/hr, reliably caused lysis of fever in 15 chronically febrile patients with Hodgkin's disease who did not have detectable bacterial, fungal, or viral infection. Antipyretic effects were also seen in some patients with reticulum cell sarcoma, lymphosarcoma, acute leukemia, histiocytic medullary reticulosis, plasma cell myeloma, carcinoma of the lung, and carcinoma of the cervix. The drug failed to produce defervescence in four patients with normal granulocyte reserves, who were febrile due to bacterial infection. When infused at a rate of 0.2 mg/kg/hr, the drug apparently caused an acute alteration of protein metabolism in man in that plasma amino acid nitrogen rose acutely while plasma levels of muramidase and ribonuclease fell during the period of the infusion. The data suggest that continuing synthesis of protein may be involved in nonbacterial fever of neoplastic disease. Mammalian granulocytes and monocytes are known to elaborate a pyrogenic protein following appropriate stimulation; it is suggested that in some types of neoplastic disease, particularly Hodgkin's disease, tumor cells may produce and release a pyrogenic protein and that drug-induced inhibition of its synthesis is responsible for the observed lysis of fever.
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PMID:Antipyretic effect of cycloheximide, and inhibitor of protein synthesis, in patients with Hodgkin's disease or other malignant neoplasms. 109 49

A chimeric mouse-human antibody (C beta 1) was constructed that recognized the principal neutralizing domain (PND) of human immunodeficiency virus type 1 (HIV-1) gp120. The constant (C) immunoglobulin regions (C gamma 1 and C kappa) of a mouse monoclonal antibody, 0.5 beta, were substituted for the human C gamma 1 and C kappa by recombining the DNA modules encoding variable or C regions. The DNA constructs were then transfected into X63 Ag8.653 myeloma cells. A clone with a high production of the chimeric antibody (C beta 1) was selected. This antibody was tested for its biological activity against HIV-1. It bound to the surface of HTLV-IIIB-infected cells and reacted with gp120/160 with equal affinity and specificity to that of the parental 0.5 beta murine monoclonal antibody in a Western blot assay. Neutralization and/or enhancement of HIV infection were evaluated with C beta 1 and 0.5 beta. Both C beta 1 and 0.5 beta neutralized cell-to-cell infection and cell-free virus infection by HTLV-IIIB. Antibody-dependence enhancement of HIV infection was not observed with either C beta 1 or 0.5 beta in the presence or absence of human complement. Antibody-dependent cell-mediated cytolysis (ADCC) and antibody-dependent complement-mediated cytolysis (ACC) were observed with C beta 1 but not with the parental 0.5 beta. These findings suggest that the neutralizing antibodies to PND may neutralize but not enhance HIV infection. Furthermore, the high levels of ACC and ADCC shown against HIV-infected cells by C beta 1 indicate that the clinical application of such monoclonal antibodies may be possible.
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PMID:Characterization of a mouse/human chimeric monoclonal antibody (C beta 1) to a principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein. 138 Feb 58

The purpose of this single arm phase II study was to test a modified version of the three drug combination vincristine, adriamycin and dexamethasone (m-VAD), in which intravenous vincristine (0.4 mg/d) and adriamycin (9 mg/m2 per day) infusions are administered for only 2 h on days 1-4 of each 28 d cycle, in patients with refractory multiple myeloma. In addition, only two 4 d courses of dexamethasone 40 mg/d was given during each cycle. The entry criteria for 44 patients included plasma cell myeloma and a measurable monoclonal peak, either refractory to initial treatment with melphalan and prednisone, or resistant to melphalan and prednisone after initially responding (resistant relapsed disease, 27 patients). Patients treated previously with chemotherapy other than melphalan and prednisone were excluded. There were no complete responses. Of the 41 evaluable patients who completed at least one course of therapy 11 had a partial response (27%, 95% C.I. 14-40%). The response rates were 19% for primary refractory disease patients, and 32% for those with resistant relapsed disease. The median duration of response was 4 months. The median survival for all 44 patients was 7.6 months (5.5 months for primary refractory patients, and 10 months for relapsed resistant disease patients). Episodes of documented bacterial infection occurred in 12 patients, and 10 patients had minor viral infection. The dexamethasone dose was reduced in 12 patients. The median neutrophil nadir was 1.2 x 10(9)/l, and median platelet nadir was 147 x 10(9)/l. Five deaths were judged as treatment related and occurred during marrow cytopenia. The results of this modified form of VAD are inferior to that reported previously for 4 d continuous infusions of vincristine and doxorubicin. This could be related to either patient selection factors, or to a reduction of the efficacy of the drug combination produced by either the shortened intravenous infusions and/or omission of one 4 d course of dexamethasone.
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PMID:Modified adriamycin-vincristine-dexamethasone (m-VAD) in primary refractory and relapsed plasma cell myeloma: an NCI (Canada) pilot study. The National Cancer Institute of Canada Clinical Trials Group. 148 35

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

Africa, the "dark continent" and the source of such wonderful tales as King Solomon's Mines and Jock of the Bushveld, has an equally enthralling story to tell about malignant disease in general and the lymphomas in particular as they occur among its varied people. It is uncertain how far back in history contact existed with the rest of the world, primarily in the form of slave trading and colonization by, among others, the Portuguese and the British. Until recent times, however, Africa's secrets have remained largely undisturbed. Fragments of medical information are recorded in the diaries of those early, intrepid explorers, such as Albert Cook, Henry Stanley, David Livingstone, and Albert Schweitzer. However, it is only in recent years that the great natural experiments that have for so long been underestimated, and very much less understood, belatedly started to attract attention. Examples are the systematic studies by Denis Burkitt, who through perseverance unraveled the lymphoma that now bears his name, and the thought-provoking description of the immunoproliferative small intestinal disease carried out by the Cape Town group, with both illustrating the axiom that "the study of man is man." Despite such occasional outstanding achievements, there is still considerable paucity of data pertaining to the various lymphoreticular malignancies, so that only limited conclusions are possible. Certainly, lymphoma in Africa differs from that elsewhere in the world. In part, this may reflect a background of immunologic disturbance attributable to parasitic infestation, viral infection, rampant malnutrition, and the impact of a wide variety of vectors, such as mosquitoes, in disease transmission. Striking differences exist in the distribution of these tumors as the incidence and pattern are followed from the equator to the milder climates in the south. This confirmed phenomenon gives rise to the tantalizing suggestion that, to some significant extent, the changes reflect the influence of geography. Thus, there may be associated alterations in the fauna and flora that determine the presence of intermediary hosts that have an impact on the eventual expression of the malignant clone. Many questions remain unanswered. For example, how can the lower incidence of Hodgkin's disease and the predominance of high-grade malignancies in the tropics and subtropics be explained? To what extent does the lymphocytic and plasmacytic hyperplasia, ascribed to intense antigenic stimulus in Burkitt's lymphoma and myeloma--perhaps even other lymphomas, such as IPSID--predispose the host to a mutational event that leads to the emergence of each distinctive neoplasm?(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The malignant lymphomas in Africa. 193 63

Interferons (IFN) are potent antiviral, cytostatic-cytotoxic and immunomodulatory agents. Although gene technology has made available an unlimited supply of all different kinds and types of IFN, their basic modes of action have not been clarified up to now. The therapeutic effects proven differ gradually between the individual disease entities. They comprise prophylaxis, prevention of recurrences and direct therapeutic effect, either of reducing the actual disease symptoms, or of inducing a complete recovery. For the following viral diseases a positive therapeutic effect has been shown: infections by herpes-viruses (herpes simplex keratitis , herpes zoster, herpes simplex), cytomegalovirus infections, chronic-hepatitis B virus infection, acute respiratory virus infections by rhino-, corona- and influenza viruses. Especially for the group of virus-associated tumors and papillomas, IFN is considered to be therapeutically effective. IFN has been accepted to be the first line treatment for laryngeal papillomatosis. In condylomata acuminata too, IFN is a potent therapeutic agent. Moreover, IFN represents the most effective therapeutic modality for Kaposi's sarcoma in patient with AIDS. Hairy cell leukemia, malignant lymphoma, multiple myeloma, melanoma and hypernephroma are the malignancies, for which a therapeutic effect of IFN could be proven. Furthermore, IFN is considered to be the therapy of first choice for hairy cell leukemias. Although there are some signs, that IFN could be a potent agent for adjuvant therapy, this question can not be answered - not even on principle - because of lacking sufficient data so far. Up to date, the therapeutic efficacy of IFN seems to be established only for hairy cell leukemia, laryngeal papillomatosis, Kaposi's sarcoma in patients with AIDS and partly for condylomata acuminata. For all other indications, first of all, sufficient phase-II-study data will have to be evaluated, before prospectively controlled studies, comparing the IFN treatment results with placebo and standard therapy results, can be initiated for the individual disease entities. Then, it will be possible to assess the therapeutic efficacy of IFN. Already now, IFN represent a valuable enrichment of the therapeutic modalities for malignancies and viral diseases.
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PMID:[Current status of interferon therapy]. 242 97


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