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)

In an individual sensitized to an antigen, Withdrawal of the corresponding antibody and of the accompanying antigen-antibody complexes stimulates antibody production: the end result is thus not unlike the effect of a booster dose of that antigen. Conversely, a sufficient concentration of antigen-antibody complexes will eventually shut off the antibody production to that antigen. The body is able to regulate through this mechanism the amplitude of the immune response, using the feed-back interaction of antigen-antibody complexes with the immune system. Without such a control system any antigenic stimulation would result in an uncontrolled out-pouring of antibodies, as is observed in myeloma. The regulation of cell mediated immunity is also indirectly affected by the concentration of circulating antigen-antibody complexes. Other mechanisms of immunoregulation are also at work, using the mediation of so-called suppressor cells, identified as sub-populations of T and B cells acting both specifically and non-specifically on immune effectors cells. It is likely that a major factor contributing to the pathogenesis of some persistent chronic infections such as syphilis, brucellosis, chronic viral hepatitis, leprosy, vaccinia, congenital cytomegalovirus infection persisting in childhood, and so on, and in conditions such as cancer, is an inadequate initial production of antibodies, further aggravated by the ensuing immunosuppression brought about by the formation of antigen-antibody complexes. Antigen-antibody complexes have indeed been identified as playing a prominent role in some of these diseases. It is also suggested that the magnitude of the initial antigenic dose may influence the ensuing immune response: while a large antigen dose could induce a "classic" and efficient immune response, a low antigen dose, such as an incipient neoplasm, could result in a minimal antibody response, further suppressed by the appearance of antigen-antibody complexes. Through this mechanism, a premature failure to eradicate the disease would follow. I suggest that a significant and sudden lowering of the concentration of relevant entibodies and antigen-antibody complexes through exchange plasmapheresis, would trigger a fully adequate and therapeutic immune response. This possibility is discussed.
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PMID:On the potential usefulness of exchange plasmapheresis in the immunotherapy of cancer and of some chronic persistent infections. 96 65

Hybridomas obtained by the fusion of spleen cells from rat cytochrome b5-immunized mice with mouse myeloma cells produced five groups of monoclonal antibodies (MAbs) with three mouse immunoglobulin subtypes: IgG1, IgG2b and IgM. All of the MAbs bound strongly to rat cytochrome b5 as measured by radioimmunoassay (RIA). Four clones of MAbs were also strongly immunoreactive with cytochrome b5 when tested by Western blotting, but only one of the MAbs (1-39-2) weakly immunoprecipitated cytochrome b5 in an Ouchterlony double-immunodiffusion test. Two of the MAbs partially inhibited cytochrome b5-mediated NADH cytochrome c reduction catalyzed by liver microsomes (24-36%). Expression of immunodetectable cytochrome b5 was highest in the liver, next highest in the kidney, and quite low in the other tissues examined with MAb 1-17-1 by Western blotting. This MAb recognized homologous cytochrome b5 of human liver microsomes and in homogenates of TK- cells infected with recombinant vaccinia virus encoding human cytochrome b5. These MAbs to cytochrome b5 will be useful for the identification, quantification, and purification of cytochrome b5 from animal and human tissues, and for understanding its role in cytochrome P450 catalyzed drug metabolism and carcinogen activation with respect to tissue, organ and individual differences.
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PMID:Monoclonal antibodies to rat liver microsomal cytochrome b5. 159 6

Peripheral blood lymphocytes from a volunteer immunized with a recombinant vaccinia virus VSC-25 expressing the gp160 env protein of HTLV-IIIB strain and from an asymptomatic HIV-infected individual were immortalized by Epstein-Barr (EBV). Clones which secrete human monoclonal antibodies from the two individuals (DZ, IgG1, lambda and C31, IgG1, kappa) were obtained and were stable for more than 2 years. The two monoclonals were directed against the gp160 env protein of HIV, DZ directed against the gp41 and C31 directed against the gp120. C31 was group-specific, whereas DZ was directed against the HTLV-IIIB and HTLV-RF strains. The epitope recognized by DZ was mapped to the carboxy terminus of the gp41, by expression of HIV DNA fragments in a yeast system and peptide analysis. The C31 epitope was not expressed by the yeast library and not present among the peptides which were tested. Monoclonal antibodies had no inhibitory effect in an HIV-induced cell fusion assay, but DZ showed a weak neutralizing activity against the HTLV-IIIB strain. Cloned EBV-transformed cell lines were fused to a murine myeloma, which allowed the heteromyeloma to be cultivated in serum-free medium. The monoclonal antibodies were produced in large quantity in a hollow-fibre reactor at defined culture conditions and purification procedures.
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PMID:Characterization and large production of human monoclonal antibodies against the HIV-1 envelope. 170 39

We have cloned and characterized a novel cellular gene that is promoted by an intracisternal A-particle (IAP) LTR and expressed in the mouse placenta (mouse IAP promoted placental gene, MIPP). A 1067bp cDNA clone containing an IAP LTR U5 region duplicated in its 5' terminus and an ORF coding for a potential 202 amino acids protein was isolated from an 8.5 day old mouse embryo cDNA library. Sequence analysis of the 5' region of a genomic clone revealed the presence of a solo IAP LTR with the same U5 duplication, and primer extension analysis confirmed that transcription of the MIPP gene is under the control of the IAP LTR. Expression of the MIPP gene parallels that of IAP genes in normal mouse tissues with abundant transcripts present in the placenta and also in the myeloma MOPC-315. The MIPP-encoded protein is composed of four 48-amino acid repeat units and shares homology with a vaccinia virus gene product. MIPP-related sequences were also detected in higher eukaryotic genomes including human.
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PMID:Identification of a novel murine IAP-promoted placenta-expressed gene. 190 5

A tumor-specific immunotherapy model was established utilizing vaccinia virus (VV) in the consideration of clinical application, in which we assessed the significance of priming of hosts with VV to induce in vivo anti-tumor immunity. C3H/HeN mice were pretreated with cyclophosphamide (Cy) to eliminate non-specific suppressor T cell activity and subsequently inoculated (primed) subcutaneously (s.c.) with 10(7)PFU of VV, leading to augmented induction of VV-reactive helper T (VV-Th) cell activities. Four weeks later, the mice were inoculated intradermally (i.d.) with syngeneic X5563 myeloma cells. Six days after the tumor cell inoculation, 5 X 10(7)PFU of VV was injected into the tumor mass 3 times at 2-day intervals. Seven of 10 mice which had received VV-priming and subsequent VV-injection into the tumor mass exhibited complete tumor regression. On the contrary, mice which had received mere intratumoral VV-injection in the absence of VV-priming failed to exhibit appreciable tumor regression. Mice (regressor mice) whose tumor had completely regressed by the above VV-immunotherapy were shown to have acquired systemic anti-tumor immunity which was confirmed by a challenge with syngeneic tumor cells after the tumor regression. In vitro analysis of these immune mice revealed that potent tumor-specific cytotoxic T lymphocyte (CTL) responses were preferentially induced, but with no detectable anti-tumor antibody responses. Such a potent tumor specific immunity was not observed in mice which had received intratumoral VV-injection in the absence of VV-priming.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Significance of priming of hosts with virus in the tumor-specific immunotherapy model utilizing virus-reactive helper T cell activity]. 252 99

It was previously demonstrated that preimmunization of mice with live vaccinia virus (VV) and subsequent immunization with VV-infected (modified), syngeneic tumor cells resulted in enhanced induction of tumor-specific immunity through a cellular collaboration between VV-reactive helper T (VV-Th) cells and tumor-specific effector cell precursors. On the basis of this augmenting system, a tumor-specific immunotherapy model was established in which a growing tumor regressed. C3H/HeN mice were pretreated with cyclophosphamide to eliminate nonspecific suppressor T cell activity and subsequently inoculated (primed) s.c. with live VV, leading to augmented induction of VV-Th cell activities. Four weeks later, the mice were inoculated i.d. with syngeneic X5563 myeloma cells. Six days after the tumor cell inoculation, live VV was injected into the tumor mass three times at 2-day intervals. Seven of ten mice which had received VV priming and subsequent VV injection into the tumor mass exhibited complete tumor regression. On the contrary, mice which had received mere intratumoral VV injection in the absence of VV priming failed to exhibit appreciable tumor regression. Mice whose tumor had completely regressed (regressor mice) by the above VV immunotherapy were shown to have acquired systemic anti-tumor immunity, which was confirmed by a challenge with syngeneic tumor cells after the tumor regression. In vitro analysis of these immune mice revealed that potent tumor-specific cytotoxic T lymphocyte responses were preferentially induced, but with no detectable anti-tumor antibody responses. Such a potent tumor-specific immunity was not observed in mice which had received an intratumoral VV injection in the absence of VV priming. Thus the results clearly indicate that the tumor regression was accompanied by concurrent generation of a potent tumor-specific immunity, suggesting that the cellular collaboration between VV-Th cells and tumor-specific effector cell precursors is also functioning in this VV-immunotherapy protocol, likewise the immunoprophylactic model. Therefore, the present model provides an effective maneuver for tumor-specific immunotherapy and this system will be theoretically applicable to human cancer treatment.
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PMID:Establishment of tumor-specific immunotherapy model utilizing vaccinia virus-reactive helper T cell activity. 297 24

Little is known about the nature of poxvirus proteins involved in the host immune response. Screening a lambda gt11 expression library of genomic rabbit poxvirus DNA with hyperimmune rabbit anti-vaccinia virus serum and selection of monospecific antibodies identified a highly antigenic viral protein of about 39,000 molecular weight (39K protein). The same-size protein of vaccinia virus was also identified with a monoclonal antibody (MAb B6) obtained from hybridomas generated after fusion of hyperimmunized mouse spleen cells with mouse myeloma cells. Structural analysis revealed that the 39K protein is an acidic polypeptide, that it can exist in two molecular forms because of intramolecular disulfide linkages, and that it is part of the virus core. This protein shares antigenic determinants with a cytoplasmic component(s) from uninfected cells. Functional studies revealed that the 39K protein is synthesized at late times postinfection and appears to be required for virus assembly. This protein is highly conserved in members of the Orthopoxvirus group, but in cowpox virus, a 41K virion protein was specifically recognized by antibodies that reacted against the vaccinia virus 39K protein. Significantly, during long-term passages of Friend erythroleukemia cells persistently infected with vaccinia virus, some virus mutants were found to increase or decrease by about 2 kilodaltons the size of the 39K protein. Mapping analysis localized sequences encoding the 39K protein in a rifampin-sensitive gene cluster between the two major core-associated viral polypeptides, 4a and 4b. The fact that the 39K core protein of vaccinia virus elicits strong humoral immune response, induces antibodies that react against a host component(s), and is subjected to genetic variability suggests that this protein has important biological functions.
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PMID:Structural and functional studies of a 39,000-Mr immunodominant protein of vaccinia virus. 331 8

The case of a 67-year-old male with IgA multiple myeloma successfully treated with AS strain of vaccinia virus is reported. The intravenous injection of this virus strain caused a definite decrease in the levels of monoclonal IgA from 1,309 mg/dl in the early stage of the treatment to 432 mg/dl on the 96th day of the regime. NK cell activity rose from 20.0% on the 10th day to 33% on the 106th day of the treatment. No adverse effects were observed throughout the entire course of the treatment. These results strongly suggest that AS strain vaccinia virus is a most promising and safe agent for the treatment of human malignancy. The possible mechanism of the beneficial effects of this virus strain is also briefly discussed.
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PMID:The effect of attenuated vaccinia virus AS strain on multiple myeloma; a case report. 362 96

Cells producing neutralizing monoclonal antibodies (mAbs) to UV-inactivated vaccinia virus strain WR were derived by fusion of hyperimmunized mouse spleen cells with mouse myeloma cells. Three mAbs that reacted strongly with purified virus envelopes as determined by enzyme-linked immunosorbent assay were studied. The three mAbs recognized a 14,000-molecular-weight (14K) envelope protein of vaccinia virus and were shown to be immunoglobulin G2b (mAbC3 and mAbB11) and immunoglobulin M (mAbF11). By using ascites, one of the antibodies, mAbC3, neutralized (50%) virus infectivity with a titer of about 10(-4), whereas the others exhibited lower neutralization titers of 10(-2) to 10(-3). The binding of the mAbs to vaccinia virus did not alter virus attachment to cells. However, virus uncoating was extensively blocked by mAbC3, whereas mAbB11 and mAbF11 had little or no effect. The three mAbs recognized a similar 14K protein in cowpox, rabbitpox, and vaccinia Elstree strains, indicating a high degree of protein conservation among orthopoxviruses. Based on the binding of mAbs to V-8 protease cleavage products of the 14K protein, the extent of protein recognition for other poxviruses, and differences in the degree of virus neutralization and of virus uncoating into cells, we suggest that the three mAbs recognize different domains of vaccinia 14K viral envelope protein. Furthermore, our findings indicate that the 14K protein may play a role in virus penetration.
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PMID:Isolation and characterization of neutralizing monoclonal antibodies to vaccinia virus. 405 58

Twenty-three patients with multiple myeloma, four patients with treated localized plasmacytoma and 14 normal subjects were immunized with keyhole limpet hemocyanin (KLH). When compared to the normal subjects, the myeloma patients showed a prolonged induction time for IgM antibody formation, a more rapid switch from IgM to IgG production and a decline in the titre of total antibody produced. In vitro lymphocyte responses to KLH following immunization were reduced in the myeloma group and tended to decline with time in a manner similar to the serum antibody concentration. Most of the myeloma patients tested developed delayed hypersensitivity skin reactions to KLH, but these reactions were smaller than those of the control subjects. The patients with myeloma had also reduced in vitro lymphocyte responses to streptolysin-O and vaccinia. Immune function of the plasmacytoma patients was similar to that of the control subjects.Both humoral and cellular immunity in response to a newly encountered antigen, KLH, is impaired in patients with multiple myeloma.
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PMID:Immune function in multiple myeloma: impaired responsiveness to keyhole limpet hemocyanin. 555 14


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