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)

Multidrug resistance (MDR) is a phenomenon by which tumor cells exposed to a single anti-proliferative agent acquire resistance to other structurally and functionally unrelated drugs. The classical form of MDR is caused by a plasma-membrane protein currently named P-glycoprotein or P-170 encoded by the human mdr-1 gene in its functional isoform. In vitro cell lines expressing P-170 usually also present phenotypic and functional alterations. In the present study we report that the cytotoxicity mediated by tumor necrosis factor alpha (TNF alpha) in MDR variants of the human T-lymphoblastoid CEM cell line is associated with apoptosis (programmed cell death). Susceptibility of MDR cells to apoptosis was increased upon cycloheximide + TNF alpha sequential treatment, whereby the impairment of protein synthesis due to the former agent was followed by the effect of cytokine exposure. Massive apoptosis of P-170-positive cells, but not of controls, was also obtained by depletion of nutrients (i.e., serum starvation). In contrast, TNF-alpha exerted a similar apoptotic effect in epithelial (MCF-7) or myeloma (S8226) drug-sensitive/ -resistant cell pairs. However, the MDR variant of myeloma S8226 was more sensitive to the cytostatic effect of TNF alpha than the parental drug-sensitive cell line. These results suggest that the presence of the MDR phenotype may be associated with increased histotype-dependent cell susceptibility to specific, protein-synthesis-independent, apoptotic pathways.
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PMID:Tumor necrosis factor alpha is a powerful apoptotic inducer in lymphoid leukemic cells expressing the P-170 glycoprotein. 876 May 94

A membrane protein (33 kDa) that binds to the globular "heads" of C1q (gC1q-R) has been recently described. The full length cDNA encoding gC1q-R has been cloned, expressed in E. coli and using the purified recombinant protein (rgC1q-R) as an immunogen, a panel of IgG monoclonal antibodies (MAb) has been produced by fusion of spleen cells from hyperimmunized BALB/c mice with NSO mouse myeloma partners. From this fusion, 60 anti-gC1q-R hybridomas were selected and evaluated for their ability to (1) discriminate between the mature form (MF) of gC1q-R (residues 74-282) and a truncated form (TF) lacking residues 74-95, which contains a major C1q binding site, (2) recognize two functionally defined synthetic peptides derived from the NH2-(XN18) and COOH-(XC15) terminus of gC1q-R, and (3) bind to microtiter well fixed intact Raji cells. Several clones were identified: MAbs 46.23 and 60.11 (IgG1 kappa), reacted strongly with ELISA plate-fixed intact Raji and K562 cells, MF, and the XN18 peptide, but had poor or no reactivity with TF; MAbs 74.5.2 > 25.15 (IgG1 kappa) recognized both MF and TF and are directed against epitopes in the XC15 peptide that contains a binding site for high-molecular-weight kininogen and Factor XII.
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PMID:Identification of functional domains on gC1Q-R, a cell surface protein that binds to the globular "heads" of C1Q, using monoclonal antibodies and synthetic peptides. 891 82

The molecular weight 30 kDa membrane protein of Toxoplasma gondii (Toxoplasma 30 kDa) apparently conserved in most strains of T. gondii and sera of infected hosts. The present study aimed to elucidate Toxoplasma 30 kDa as a useful diagnostic antigen for serodiagnosis of toxoplasmosis by ELISA and for induction of protective immunity. Murine spleen cells immunized with the membrane antigen of T. gondii were fused with mouse Sp2/O-Ag14 myeloma cells. Out of 8 clones selected, five were IgG2b, the others belonged to IgG1 and IgG2a. The 30 kDa antigen was distributed mainly on the surface membrane of tachyzoites by indirect fluorescence method. Murine peritoneal macrophages which were activated by 30 kDa antigen produced more amounts of NO2 compared with crude antigen-treated group, however there were no significant differences in toxoplamacidal activity between the two groups. Higher specificity of Toxoplasma 30 kDa antigen was recognized for serodiagnosis of toxoplasmosis than the crude antigen. From these results, Toxoplasma 30 kDa antigen enhances the cytotoxic effect of macrophages as well as a more reliable means for the serodiagnosis of toxoplasmosis by ELISA.
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PMID:[Immunological properties of the 30 kDa antigen of toxoplasma gondii]. 910 Apr 40

A family of cytokines [IL-6, IL-11, oncostatin M (OM), leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF) and cardiotrophin-1] involved in various inflammatory or tumoral diseases share the same gp130 signal transducer chain. The complex formed with their specific receptors associates with a common transducing gp130 membrane protein (gp130) resulting in the formation of high avidity receptor and activation of tyrosine kinases. With the view of identifying gp130 domains specifically involved in IL-6 signalling, the authors prepared 37 new anti-gp130 mAb and analysed the structure-function relationship of the molecule. By cross-competition ELISA, the mAb were classified in 10 subgroups called A to J. By ELISA and BIAcore analysis, the mAb were found to recognize at least 18 antigenic specificities of the gp130 chain. The mAb reacted against the soluble and the membrane forms of gp130 as well. Their ability to inhibit the proliferation of the human myeloma cell line XG-4 of which the growth is strictly dependent on the presence of either exogenous IL-6, or LIF, or OM, or CNTF was studied. Besides mAb with no evident neutralizing effect (G and H) and mAb which neutralized equally well the activity of all tested cytokines (all mAb of groups A, I and J), some showed a selective effect. Those of group F inhibited also the proliferation induced by the 4 cytokines, but more specifically that dependent on the CNTF. mAb of groups B and E specifically inhibited the growth induced by IL-6, whereas those of group C inhibited that induced by LIF and OM. These results show the presence of different gp130 epitopes specifically involved in the signaling induced by the cytokines of the gp130 family. In ELISA, only mAb of group B and E were found to inhibit the binding of the IL-6-IL-6R complex to gp130, showing that they identified one or two domains of gp130 involved in its interaction with the IL-6-IL-6R complex. Precise identification of this(ese) epitope(s) would be useful to better understand the mechanisms of the IL-6 signalling.
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PMID:Specific inhibition of IL-6 signalling with monoclonal antibodies against the gp130 receptor. 911 31

The possibility has been raised that either a human herpesvirus-8 (HHV-8) variant or a novel, unidentified, gamma-herpesvirus related to HHV-8 is frequently associated with multiple myeloma (MM), which could explain the lack of antibodies to HHV-8 antigens and the discordant results from polymerase chain reaction (PCR) studies of HHV-8-specific sequences in MM patients. Thus, we used a sensitive PCR assay with degenerate primers targeting the highly conserved DNA polymerase gene of the herpesvirus family to examine the long-term cultures of bone marrow stromal cells (BMSCs) from 19 MM, 3 monoclonal gammopathies of undetermined significance and 6 control patients. Both the culture supernatant and the adherent stromal layer were examined from the 2nd until the 8th week of culture to assess the immunophenotype of the various cell types harvested for the molecular analysis. BMSCs consisted of a mixed population of fibroblast, macrophage, dendritic and endothelial cells. An amplified product of the expected size was obtained only in 3 MM cases, both in the adherent and nonadherent fractions. Direct sequencing and alignment of the nucleotide and amino acid sequences showed that the DNA sequences were 100% identical to Epstein-Barr virus (EBV) DNA. The PCR positivity was due to the presence of EBV-infected lymphoblastoid cells with plasmacytoid features, expressing the EBV-encoded latent membrane protein-1 and detectable either in the stromal cells or in the culture supernatant. Our data do not support a causal role of either HHV-8 or a novel herpesviral variant related to HHV-8 in MM.
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PMID:PCR with degenerate primers for highly conserved DNA polymerase gene of the herpesvirus family shows neither human herpesvirus 8 nor a related variant in bone marrow stromal cells from multiple myeloma patients. 1072 98

Since several forms of autoimmunity have been associated with urticaria, we performed a detailed survey of autoantibodies in patients with idiopathic subacute and chronic urticaria. Sera from 25 consecutive patients referred for evaluation of urticaria were tested for the presence of autoantibodies and compared to sera from seventy-five control samples examined from individuals being treated for other allergic diseases. Study patients ranged in age from 15 to 73 years, with a mean of 48. One patient had a diagnosis of inflammatory bowel disease and one had multiple myeloma, but otherwise there were no other diagnoses of disease specifically involving immunity other than atopy. No study patients had a concurrent diagnosis of autoimmune thyroid disease. The test sera were examined for autoantibodies and for antibodies to H. pylori. Antibodies to thyroid peroxidase (TPO) were found significantly (p < 0.01) more common in urticaria (20%] than in controls (0%). Rheumatoid factor(RF) was also found in significantly (p < 0.05) increased in urticaria (16%) compared to controls [0%). Neither H. pylori antibody nor other autoantibodies were present in significant numbers of urticaria patients when compared to controls. Tested autoantibodies included those to thyroglobulin, sDNA, SSA/SSB, ENA, cardiolipin, beta2-glycoprotein I, myeloperoxidase, proteinase-3, smooth muscle, ANA, human lysosomal-associated membrane protein, and bactericidal permeability increasing protein. Thus, patients with urticaria were somewhat more likely to have a thyroid autoantibody to TPO or to have RF. This survey demonstrates that while some markers of autoimmunity may be increased in urticaria patients, broad nonspecific autoimmunity is not found.
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PMID:Are autoantibodies present in patients with subacute and chronic urticaria? 1143 65

Vaccine-based strategies are currently under investigation as a means of inducing tumour-specific immune responses and improving the clinical outcome of multiple myeloma (MM) patients in remission after high-dose chemotherapy and peripheral blood progenitor cell (PBPC) infusion. The immune competence of these patients was investigated by determining the overall diversity of the T-cell receptor (TCR) repertoire in the peripheral blood (PB) and bone marrow (BM). The average time after transplantation was 13 months. The clonality and reciprocal usage of BV gene segments (TCRBV repertoire) was estimated at the cDNA level and membrane protein expression. The TCRBV repertoire of MM was severely disrupted compared with age-matched normal donors. On average, one-third of the total repertoire in both the PB and the BM consisted of T cells expressing oligoclonal TCRbeta transcripts. Flow cytometry showed an increased frequency of abnormally expanded BV subfamilies at both sites. BV expansions were predominantly CD8+ and had the phenotype of antigen-experienced memory T cells as well as T cells with the naive phenotype. Oligoclonality was not restricted to phenotypically expanded BV subfamilies, but also involved normally represented BV subfamilies. The TCR repertoire of MM in remission was then compared with monoclonal gammopathy of undetermined significance (MGUS) and MM patients at diagnosis. The degree of TCR diversity was similar in age-matched normal donors and MGUS, but progressively decreased from MGUS to MM at diagnosis and then to MM in remission. These data indicate that: (1) there is a long-lasting and severe disruption of TCR diversity after high-dose chemotherapy and PBPC infusion, and (2) the extent of TCR disruption may affect the clinical outcome of vaccine-based strategies delivered at the stage of minimal residual disease.
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PMID:Severe and long-lasting disruption of T-cell receptor diversity in human myeloma after high-dose chemotherapy and autologous peripheral blood progenitor cell infusion. 1144 2

Specific modified substrate-analogous amino acids and peptides have been used as affinity ligands in the affinity chromatography of proteases. Alanine methyl ketone-Sepharose (AMK-Sepharose) is introduced as affinity support for the purification of a bacterial alanyl aminopeptidase (AAP) from a membrane protein extract and Arginine-Agarose as support for the preparation of a membrane-bound proteinase of myeloma cells (MP-1). Peptidyl methyl ketones as affinity ligands have been used to separate subtilisin enzymes and the cysteine proteases cathepsin B, L, and S. As a new type of ligands, spacer-bound peptidyl chloromethyl ketones are presented for a specific and oriented immobilization of proteinases. Oriented-immobilized cathepsin B was used to isolate antibodies against this enzyme.
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PMID:Purification of soluble and membrane-bound proteases with substrate-analogous inhibitors by affinity chromatography. 1169 97

Moraxella catarrhalis IgD-binding protein (MID), a 200-kDa outer membrane protein comprising 2,139 amino acids, has recently been isolated and shown to display a unique and specific affinity for human IgD. To identify the IgD-binding region, MID was digested with proteases. In addition, a series of truncated fragments of MID were manufactured and expressed in Escherichia coli followed by analysis for IgD binding in Western and dot blots. The smallest fragment with essentially preserved IgD binding was comprised of 238 amino acid residues (MID(962-1200)). Shorter recombinant proteins gradually lost IgD-binding capacity, and the shortest IgD-binding fragment comprising 157 amino acids (MID(985-1142)) displayed a 1,000-fold reduced IgD binding compared with the full-length molecule. The truncated MID(962-1200) was efficiently attracted to a standard IgD serum and to purified myeloma IgD(kappa) and IgD(lambda) sera but not to IgG, IgM, or IgA myeloma sera. Furthermore, the fragment specifically bound to peripheral blood B lymphocytes, and the binding was inhibited by preincubation with anti-IgD-Fab polyclonal antibodies. Results obtained by introducing five amino acids randomly into MID(962-1200) using transposons suggested that alpha-helix structures were important for IgD binding. Ultracentrifugation experiments and gel electrophoresis revealed that native MID(962-1200) was a tetramer. Interestingly, tetrameric MID(962-1200) attracted IgD more than 20-fold more efficiently than the monomeric form. Thus, a tetrameric structure of MID(962-1200) is crucial for optimal IgD-binding capacity.
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PMID:The immunoglobulin D-binding part of the outer membrane protein MID from Moraxella catarrhalis comprises 238 amino acids and a tetrameric structure. 1211 Jun 69

SZ-51, a murine monoclonal antibody (McAb) specific for alpha-granule membrane protein (GMP-140) on the surface of the activated human platelets, has shown promise for thrombus imaging and thrombolysis. In order to reduce the immunogenicity of the murine McAb SZ-51 in man and to obtain a high level of antibody production, we constructed two chimeras (alpha-Lys17-51BVK/Hu, alpha-Lys30-51VH/Hu) by joining the variable regions gene of mouse antibody to the constant regions gene of human immunoglobulin (Ig)(gamma1,k). Both chimeric genes were cloned into two selectable expression vectors separately, which were co-transfected into a non-Ig secreting murine myeloma cell line SP2/0 with the Lipofectin reagent. One transfectoma, which showed stable antigen (GMP-140) binding ability and a high level expression of 5 mg/L, was obtained. Immunoblotting analysis demonstrated that the chimeric antibody in the supernatant, like the native mouse SZ-51, had the characteristic of binding to GMP-140. In addition, the chimeric antibody can bind competitively to activated platelets with (125)I-labeled mouse SZ-51. Therefore, the SZ-51 chimeric antibody may be a potential agent for the diagnosis and therapy of thrombotic diseases in future.
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PMID:Construction and Expression of Mouse-human Chimeric Antibody SZ-51 Specific for Human Activated Platelets. 1223 6


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