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 antigenic properties of 21 Japanese field isolates and two Australian strains of Akabane (AKA) virus (Simbu serogroup, bunyavirus) isolated from 1959 to 1990 were compared by enzyme-linked immunosorbent assay (ELISA), plaque-reduction neutralization (PRNT) and hemagglutination inhibition (HI) tests using monoclonal antibodies (Mabs) to the OBE-1 strain of AKA virus. Sixteen Mabs were established by fusing P3X63Ag8U1 mouse myeloma cells and spleen cells from BALB/c mice immunized with the OBE-1 strain. Of the 16 clones, 13 produced immunoglobulin (Ig) which precipitated glycoprotein G1 and three produced Ig which precipitated nucleoprotein (N). Twelve out of 13 Mabs had both NT and HI activities to not only the homologous OBE-1 strain but also the other isolates. By the competitive binding assay, at least five antigenic regions for G1, and two for N were defined. Some of the anti-G1 Mabs which reacted to the same antigenic region had unique reactivity while anti-N Mabs recognizing the same epitope reacted with almost the same degree to all of the isolates. Finally, nine epitopes of the G1 protein in five different antigenic regions have been identified. There was no striking correlation between isolation date and place of the isolates and their reactivity to Mabs. A most interesting result is that three isolates collected in the same place over a three week period had different reactivity patterns detected by ELISA, showing great antigenic variation of the virus. AKA virus may be a single gene pool consisting of different genotypes in the field.
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PMID:Antigenic diversity of Akabane virus detected by monoclonal antibodies. 908 50

Monoclonal antibodies (MoAbs) specifically against Japanese encephalitis virus (JEV) were generated by fusion of immunized mouse spleen cells with NS-1 myeloma cells. Nakayama-NIH (Na) and three Taiwan local strains of JEV, i.e., TL isolated from a patient's brain in 1965, NT109 (JE7) isolated from Cx. tritaeniorhynchus in 1985, and RP9, a plaque purified clone of NT109, were used in the immunization. The specificities of moAbs were determined by immunoprecipitation and western blotting, using JEV-infected cell lysates. They were confirmed by the same methods using recombinant JEV proteins as antigens. From Na immunization, 4 anti-E, 3 anti-NS1 and 3 anti-NS3 moAbs were generated. Seventeen anti-E, three anti-NS1 and three anti-NS3 specific moAbs were generated from mice immunized with Taiwan local JEV strains. Overall 21 anti-E, 6 anti-NS1, and 6 anti-NS3 moAbs were produced and characterized. The isotypes of these moAbs were also determined and described. Interestingly, a majority of the moAbs generated for RP9 were IgG1 isotype. In conclusion, 33 moAbs specific to JEV were generated and characterized, and some of these anti-JEV moAbs were made against Taiwan local isolates. These moAbs provide a powerful tool to study JEV, especially the antigenic properties of Taiwan's local strains.
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PMID:Generation and characterization of Japanese encephalitis virus specific monoclonal antibodies. 977 91

Recombinant adenovirus (AdV) vectors are highly efficient at in vitro and in vivo gene delivery. VKCK is a murine myeloma cell line expressing the light chain of the fusion protein RM4/tumor necrosis factor (TNF)-alpha. The in vitro transfection of VKCK cells with the AdV AdV5LacZ, which contains the marker gene beta-galactosidase, can reach a maximal 75% at a multiplicity of infection of 1000. Intratumoral injections of AdV5LacZ (2 x 10(9) plaque-forming units) resulted in substantial gene transfer in nearly 50% of VKCK tumors. The AdV pLpA/M4-TNF-alpha, which contains a fused gene M4-TNF-alpha that codes for the heavy chain of fusion protein RM4/TNF-alpha, was constructed. After the in vitro transfection of pLpA/M4-TNF-alpha at a multiplicity of infection of 1000, transfected VKCK cells showed significant secretion of RM4/TNF-alpha (36 ng/mL/10(6) cells) containing the functional TNF-alpha moiety in tissue culture. The secretion peaks at day 3 and is diminished at day 6 following the viral infection. These transfected VKCK cells also became more immunogenic with enhanced expression of major histocompatibility complex class I antigen. Intratumoral injections of 2 x 10(9) plaque-forming units of pLpA/M4-TNF-alpha virus with a repeated booster resulted in significant VKCK tumor regression in immune-competent mice, but not in athymic nude mice with a mean tumor weight of 0.07 g that were compared with 1.58 g and 1.70 g for tumors injected with AdV5LacZ and phosphate-buffered saline, respectively (P < .01). The tumor regression also results in protective immunity against a second challenge with parental tumor cells, which is mainly mediated by VKCK tumor-specific CD8+ T cells. These results indicate that AdV-mediated cytokine gene therapy may be a useful approach in the clinical management of solid human tumors.
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PMID:Intratumoral vaccination of adenoviruses expressing fusion protein RM4/tumor necrosis factor (TNF)-alpha induces significant tumor regression. 991 92

Human herpesvirus 8 (HHV-8, also called KSHV) is linked to the etiopathogenesis of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). The universal presence of HHV-8 in early KS has not yet been shown. We used a mAb (LN53) against latent nuclear antigen-1 (LNA-1) of HHV-8 encoded by ORF73 to study the distribution of the cell types latently infected by HHV-8 in patch, plaque, and nodular KS, MCD, and PEL. In early KS, HHV-8 is present in <10% of cells forming the walls of ectatic vessels. In nodular KS, HHV-8 is present in cells surrounding slit-like vessels and in >90% of spindle cells, but not in normal vascular endothelium. In addition, HHV-8 colocalizes with vascular endothelial growth factor receptor-3 (VEGFR-3), a marker of lymphatic and precursor endothelium. In early KS lesions, VEGFR-3 is more extensively expressed than LNA-1, indicating that HHV-8 is not inducing the proliferation of VEGFR-3-positive endothelium directly. In MCD, HHV-8 is present in mantle zone large immunoblastic B cells. No staining for LNA-1 is seen in samples from multiple myeloma, prostate cancer, and angiosarcoma, supporting the absence of any etiological link between these diseases and HHV-8.
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PMID:Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. 1020 Feb 99

We examined dengue virus immune complex-phagocyte interaction with respect to a single Fc receptor class using a transient expression system involving the high-affinity human macrophage receptor, FcgammaRI. We found that New Guinea C strain dengue 2 virus formed well-defined plaques in normal and transfected COS cells and we analyzed the structural determinants of FcgammaRI-mediated binding and internalization of dengue 2 virus immune complexes by expressing native or truncated forms of the receptor in COS cells, alone or with its accessory gamma chain signaling unit, which bears an immunoreceptor tyrosine-based activation motif (ITAM). The residual infectivity of dengue 2 virus treated with neutralizing human antiserum was strikingly higher in FcgammaRI-bearing COS cells than in controls. Compatible with the IgG subclass specificity of FcgammaRI, this difference was abrogated quantitatively by treatment of FcgammaRI-transfected cells with human IgG1 but not IgG2 myeloma protein. The magnitude of receptor-mediated plaque formation after cotransfection with gamma chain was also significantly higher than in controls but was less than that observed with FcgammaRI transfection only, a difference probably explained by reduced levels of FcgammaRI expression in gamma chain cotransfectants. Deletion of the FcgammaRI cytoplasmic domain had no effect on receptor-mediated immune complex infectivity. We conclude that the FcgammaRI extracellular domain is sufficient for internalization of infectious dengue virus immune complexes through a mechanism that does not involve classical ITAM-dependent signaling.
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PMID:Influence of the human high-affinity IgG receptor FcgammaRI (CD64) on residual infectivity of neutralized dengue virus. 1040 59

Activating point mutations in codons 12, 13, or 61 of the K-ras and N-ras genes have been reported to occur in up to 40% of patients with multiple myeloma at presentation. In a study of 34 presentation myeloma cases using a sensitive polymerase chain reaction-restriction fragment length polymorphism strategy on enriched tumor cell populations, the present study detected N-ras codon 61 mutation-positive cells in all patients. Quantitative plaque hybridization using allele-specific oligonucleotide probes showed that in the majority of patients, ras mutation-positive cells comprise only a subpopulation of the total malignant plasma cell compartment (range, 12%-100%). Using clonospecific point mutations in the 5' untranslated region of the BCL6 gene to quantitate clonal B cells in FACS-sorted bone marrow populations from 2 patients, the representation of ras mutation-positive cells was independent of immunophenotype. These observations imply that mutational activation of N-ras codon 61 is a mandatory event in the pathogenesis of multiple myeloma; such mutations provide a marker of intraclonal heterogeneity that may originate at an earlier ontologic stage than immunophenotypic diversification of the malignant B cell clone.
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PMID:Detection of N-Ras codon 61 mutations in subpopulations of tumor cells in multiple myeloma at presentation. 1215 Jan 55

Antibodies reactive with phosphorylcholine (PC) are ubiquitous in human sera, but the antigens stimulating their production and their function are not clear. Previous studies have shown that a significant proportion of dental plaque bacteria contain PC as determined by reactivity with PC-specific mouse myeloma proteins and monoclonal antibodies. Additionally, serum antibody concentrations of immunoglobulin (IgG) G anti-PC are higher in sera of individuals who have experienced periodontal attachment loss than those who are periodontally healthy. These data implicate the oral microflora as a source of antigen-stimulating anti-PC responses. Recent data also indicate that antibodies with specificity for PC are elevated in ApoE-deficient mice, a model for studies of athersclerosis, and that such antibodies bound oxidized low-density lipoproteins (LDL) (oxLDL) in atherosclerotic plaques. These data prompted the hypothesis that human anti-PC could bind to both oral bacteria and human oxLDL, and that these antigens are cross-reactive. We therefore examined the ability of human anti-PC to bind to PC-bearing strains of oral bacteria using enzyme-linked immunosorbent inhibition assays and by assessment of direct binding of affinity-purified human anti-PC to PC-bearing Actinobacillus actinomycetemcomitans. Our results indicated that PC-bearing strains of Streptococcus oralis, Streptococcus sanguis, Haemophilus aphrophilus, Actinomyces naeslundii, Fusobacterium nucleatum, and A. actinomycetemcomitans, as well as a strain of Streptococcus pneumoniae, absorbed up to 80% of anti-PC IgG antibody from human sera. Furthermore, purified anti-PC bound to a PC-bearing strain of A. actinomycetemcomitans but only poorly to a PC-negative strain. OxLDL also absorbed anti-PC from human sera, and oxLDL but not LDL reacted with up to 80% of the anti-PC in human sera. Furthermore, purified anti-PC bound directly to oxLDL but not to LDL. The data indicate that PC-containing antigens on a variety of common oral bacteria are cross-reactive with neoantigens expressed in oxLDL. We propose that PC-bearing dental plaque microorganisms may induce an antibody response to PC that could influence the inflammatory response associated with atherosclerosis.
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PMID:Phosphorylcholine-dependent cross-reactivity between dental plaque bacteria and oxidized low-density lipoproteins. 1159 29

The coexistence of multiple myeloma (MM) and mycosis fungoides (MF), and hence of both B- and T-cell neoplastic clones, is a rare event. We describe a case of plaque-stage MF associated with IgG lambda MM. The clinical onset of MF preceded that of MM, supporting the hypothesis that MF predisposed to the development of the B-cell proliferative disorder. The skin tumor cells were found to originate from CD4(+) T-lymphocytes, characterized by a V beta 8 receptor and no proviral human T-lymphotropic virus (HTLV)-I monoclonal integration. They also displayed a polarized Th1-type cytokine profile containing mRNAs for interleukin (IL)-2, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-beta, but not for IL-4, IL-5, or IL-10. The CD8(+)/CD57(+) suppressor-cytotoxic subpopulation was significantly increased in the peripheral blood and was associated with MM progression. Expression of p16INK4A, a gene from the INK family that inhibits cyclin-dependent kinases and regulates the cell cycle, was lacking in MF cells and bone marrow (BM) plasma cells. The p16INK4A gene was silenced by hypermethylation, suggesting that it plays a role in the early phase of the pathogenesis of both diseases. Thus, a lymphoid precursor cell presumably contains aberrations that induce the development of both clonal diseases in a multistep process.
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PMID:Multiple myeloma and mycosis fungoides in the same patient: clinical, immunologic, and molecular studies. 1210 63

Targeting tumor-associated vascular endothelium by replication-competent viral vectors is a promising strategy for cancer gene therapy. Here we describe the development of a viral vector based on the Edmonston vaccine strain of measles virus targeted to integrin alpha(v)beta3, which is expressed abundantly on activated but not quiescent vascular endothelium. We displayed a disintegrin, M28L echistatin that binds with a high affinity to integrin alpha(v)beta3 on the COOH terminus of the viral attachment (H) protein and rescued the replication-competent recombinant virus by reverse genetics. The new targeted virus was named measles virus echistatin vector (MV-ERV). Its native binding to CD46 was purposefully retained to allow virus infection of tumor cells expressing this receptor. MV-ERV correctly displayed echistatin on the outer surface of its envelope and produced interesting ring formation phenomena due to cell detachment upon infection of susceptible Vero cells in vitro. MV-ERV grew to 10(6) plaque-forming units/mL, slightly lower than the parental Edmonston strain of measles virus (MV-Edm), but it selectively infected Chinese hamster ovary cells expressing integrin alpha(v)beta3. It also selectively infected both bovine and human endothelial cells on matrigels and unlike MV-Edm, MV-ERV infected newly formed blood vessels in chorioallantoic membrane assays. In animal models, MV-ERV but not the control MV-Edm caused the regression of s.c. xenografts of resistant multiple myeloma tumors (MM1) in severe combined immunodeficient mice. The tumors were either completely eradicated or their growth was significantly retarded. The specificity, potency, and feasibility of MV-ERV infection clearly show the potential use of MV-ERV in gene therapy for targeting tumor-associated vasculature for the treatment of solid tumors.
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PMID:Targeted measles virus vector displaying echistatin infects endothelial cells via alpha(v)beta3 and leads to tumor regression. 1595 76

Dengue virus (DEN), the pathogen behind dengue hemorrhagic fever, remains a public health problem in Asia and South America. In this study, monoclonal antibodies (MAbs) against DEN serotype 1 (DEN-1) were generated by fusing NSI/1-Ag4-1 mouse myeloma cells with lymphocytes from BALB/c mice immunized with DEN-1. Twelve MAbs were found to react specifically to the DENs by enzyme-linked immunosorbent assay, immunofluorescence analysis, and immunoblotting analysis. Five MAbs, namely, DA4-7, DA6-7, DA9-5, DA10-2, and DA11-13, were found to react with envelope proteins of DEN-1. Two serotype-specific MAbs of DEN-1, DA6-7 and DA11-13, were further shown to neutralize DEN-1 infection by a plaque reduction neutralization test. The neutralizing epitopes of these MAbs were further identified from a random peptide library displayed on phage. Immunopositive phage clones reacted specifically with these MAbs and did not react with normal mouse serum. Epitope-based peptide antigens were proved able to detect antibodies in serum samples collected from DEN-1-infected patients but not in those taken from DEN-2-infected patients or healthy controls. We believe that these MAbs and neutralizing epitopes will provide information that will lead to the development of DEN-1 serotype-specific diagnostic reagents and vaccines.
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PMID:Generation and characterization of monoclonal antibodies against dengue virus type 1 for epitope mapping and serological detection by epitope-based peptide antigens. 1728 14


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