UMLS:C0026764 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0026764 (multiple myeloma)
36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hybridization of a non-secreting mouse myeloma cell line NSO with splenocytes from a BALB/c mouse hyperimmunized with the anti-CD4 monoclonal antibody (mAb) HP2/6 generated the anti-idiotypic (anti-id) mAb F11-2113, F11-2302 and F11-2444, which recognize idiotope(s) (id) that are the same or spatially close to each other and are located outside the antigen-combining site of the immunizing mAb. Binding and inhibition assay showed that id are not expressed either on other mouse anti-CD4 mAb or polyclonal immunoglobulins (Ig). Western blotting analysis showed that the id defined by anti-id mAb F11-2113, F11-2302 and F11-2444 are similarly expressed on separated heavy and light chains of mAb HP2/6 and suggested they are likely to be 'sequence-dependent' since their expression is conserved following SDS and reducing reagents treatment. This finding is unique inasmuch as 'sequence-dependent' id similarly expressed on heavy and light chains have been described only on a mouse monoclonal auto-antibody with immunoregulatory properties.
...
PMID:Anti-idiotypic monoclonal antibodies reacting with idiotope on isolated-denatured chains of an anti-CD4 monoclonal antibody. 178 32

That structural abnormalities may be responsible for nonamyloid immunoglobulin (Ig) light chain deposition disease (LCDD) is suggested by previous results of Ig biosynthesis studies, but this hypothesis was not documented at the molecular level. We report on the first complete primary sequence deduced from cDNA analysis of a kappa light chain responsible for LCDD associated with an apparently nonsecretory myeloma. Bone marrow myeloma cells contained intracellular kappa chains and no heavy chains by immunofluorescence. Kidney biopsy showed typical nonamyloid PAS-positive kappa chain deposits. SDS-PAGE analysis of material extracted from a kidney biopsy specimen and of Ig produced by the myeloma cells revealed kappa chains of abnormally high apparent molecular mass (30,000). Comparison of the NH2-terminal aminoacid sequence of the kappa chain deposited in the kidney and of the complete sequence of several identical kappa cDNA clones from bone marrow cells showed the identity of the tissue deposited and plasma cell kappa chain. The kappa mRNA had an overall normal structure and corresponded to the V kappa IV gene rearranged to J kappa 1 and followed by a normal constant exon of the Km(3) allotype. The variable sequence differed from the V kappa IV germline gene by nine point mutations, including an Asp----Asn substitution at position +70 resulting in a potential N-glycosylation site. In vitro biosynthesis experiments and treatment with N-glycosidase provided evidence for the intracellular glycosylation of the monoclonal kappa chain. The peculiar sequence and the glycosylation of a kappa chain of the rare V kappa IV subgroup might be responsible for structural abnormalities leading to tissue deposition.
...
PMID:Structure of a monoclonal kappa chain of the V kappa IV subgroup in the kidney and plasma cells in light chain deposition disease. 190 72

Glucocorticoids are widely used for the treatment of multiple myeloma. To investigate the direct actions of glucocorticoids on myeloma cells, we have used three cell lines of human multiple myeloma, OPM-1, OPM-2, and RPMI 8226. When growth curves of these cells were examined, OPM-1 cells were resistant, while OPM-2 were sensitive to dexamethasone (DEX). In cultures of OPM-2 cells, addition of DEX led to virtual cessation of growth, with only 16% of the residual cells viable after 4 days. RPMI 8226 appeared to be slightly sensitive, showing some slowing of growth for several days in DEX, with later recovery. Viabilities of OPM-1 and RPMI 8226 cells were not affected. Secretion of immunoglobulin (Ig-lambda) was also partially suppressed, by 30% in OPM-2 and 14% in OPM-1. No significant suppression was observed in RPMI 8226. To explore the mechanism of these differential responses to the steroid, glucocorticoid receptor (GR) was examined. Binding assays showed high affinity binding sites in all three cell lines: 64 +/- 11 fmol/10(6) cells in OPM-1, 78 +/- 14 in OPM-2, and 62 +/- 16 in RPMI 8226. Nuclear transfer of GR and DNA-cellulose binding after heat activation appeared similar in all three cell lines. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cytosol proteins labeled with [3H]dexamethasone mesylate showed a GR of Mr 95,000 in all three. When GR mRNA was studied in these cells, all of them had GR mRNA of approximately 7 kilobases, but OPM-2 and RPMI 8226 had 3 times more GR mRNA than OPM-1. OPM-2 GR mRNA was induced 2-fold by DEX treatment at 5 x 10(-9) M or greater. OPM-1 GR mRNA was much less sensitive, with no response at less than 10(-6) M DEX and only 1.5-fold induction at that concentration. These results demonstrate that some myeloma cells can be killed by a direct action of glucocorticoids. The quantity and affinity of GR in the cells were not predictive of this response. Therefore, we propose that the resistance of OPM-1 and the relative resistance of RPMI 8226 to glucocorticoid inhibition of cell growth is by post-receptor mechanisms. The high sensitivity of induction of GR mRNA in OPM-2 may correlate with glucocorticoid-evoked cell kill.
...
PMID:Glucocorticoid effects on myeloma cells in culture: correlation of growth inhibition with induction of glucocorticoid receptor messenger RNA. 210 90

Immunoglobulin- or multiple myeloma-associated amyloidosis has been distinguished by the tissue deposition of Congophilic, fibrillar protein consisting of light chains or light-chain fragments (AL amyloidosis). We now report the isolation and characterization of another form of immunoglobulin-associated amyloid obtained from a patient who had extensive systemic amyloidosis and in whom the amyloid deposits consisted not of light chains but rather of an unusual form of heavy chain. This component, isolated from splenic amyloid extracts, represented an internally deleted IgG1 heavy chain as evidenced by immunochemical, electrophoretic, and amino acid sequence analyses. A comparable immunoglobulin-related monoclonal protein, consisting only of IgG heavy chains, was present in the patient's urine. Based on serologic reactivity with a battery of anti-immunoglobulin antisera, these two immunoglobulin-related components were antigenically identical; however, when compared to normal IgG, both were deficient in Fc-associated gamma-chain determinants. The structural abnormality of the amyloid gamma-chain protein was further evidenced by SDS/PAGE and immuno-blotting analyses: An unusually low molecular mass of approximately 22 kDa was found for this material vs. the expected value of approximately 55 kDa for a normal gamma heavy chain. Despite the lack of certain Fc determinants, the amyloid and urinary heavy-chain proteins expressed the IgG1 subclass allotype marker G1m(a) located on the third constant region (CH3) domain of the internally deleted IgG1 heavy chains. That the amyloid protein contained an intact CH3 domain was established through amino acid sequence analyses of cyanogen bromide fragments and peptides generated by a lysine-specific protease. These studies also revealed that the gamma-chain amyloid protein contained the complete heavy-chain variable (VH) domain [including the diversity (DH) and joining (JH) segments] that was contiguous with the CH3 domain. The low molecular mass of the protein resulted from the total absence of the first (CH1), hinge, and second (CH2) heavy-chain constant regions. Such extensive CH deletions and the presence of a complete VH distinguish this amyloid-associated heavy chain from all other heretofore characterized gamma-heavy-chain disease proteins. This heavy-chain-related form of immunoglobulin-associated amyloidosis is tentatively designated AH amyloidosis.
...
PMID:Immunoglobulin heavy-chain-associated amyloidosis. 211 50

Spleen cells of BALB/c mice immunized with human pulmonary adenocarcinoma cell LTEP-a2 were fused with murine myeloma cell SP 2/0, from which 4 hybridomas (2 A7, 2 E9, 4 F2 and 5 F11) were obtained. Indirect immunofluorescence test showed that these 4 monoclonal antibodies reacted with human lung cancer cells, but not with 2 BS or the lymphocytes and red blood cells in 4 different ABO groups of 10 persons. Using ABC immunoperoxidase stain technique, these 4 antibodies showed negative reaction with 9 tissue types from the normal subject and fetus but could react with 52-83% of the 29 human lung carcinomas and 64-92% of the 24 non-small cell lung cancers (non-SCLC). When 5 F11 was combined with 2 A7 or 2 E9, the percentage of positive stain was 100% in 24 non-SCLC. The results of indirect immunofluorescence stain showed that strong membrane stain by 5 F11 and membrane stain by 4 F2 were obtained, indicating that these antibodies could recognize antigens on cancer cell membrane. It is suggested that a mixture of 5 F11 and other antibodies be useful in the diagnosis and treatment of lung cancer. Molecular weight of the antigens recognized by the 4 antibodies was determined by SDS-PAGE and immunoblot technique to be 47 KD (2 A7), 67 KD (2E9), 40 KD (4F2) and 56 KD (5 F11).
...
PMID:[Monoclonal antibody against human lung carcinoma]. 217 66

A case of acquired von Willebrand disease (AvWD) associated with an IgA lambda multiple myeloma is reported. No form of inhibitor could be detected. SDS-agarose gel electrophoresis patterns of von Willebrand factor (vWF) both in plasma and platelet lysates were normal but a decrease in all-sized multimers with a type IA pattern was seen. After 1-deamino-8-D arginine vasopressin (DDAVP) infusion, vWF multimers larger than those seen in the resting state appeared in patient plasma, which were progressively cleared. Indirect immunofluorescence studies with a monoclonal antibody to vWF showed that vWF was selectively absorbed into myelomatous cells. This is the first case of AvWD associated with multiple myeloma resulting from the selective absorption of vWF into abnormal plasma cells. This feature established a new pathophysiological mechanism of AvWD in multiple myeloma and probably in other lymphoproliferative diseases.
...
PMID:Acquired von Willebrand disease in multiple myeloma secondary to absorption of von Willebrand factor by plasma cells. 220 95

Rearrangements of immunoglobulin genes are mediated by highly conserved heptamer and nonamer recombinational signal sequence. Using a protein-blotting procedure, a heptamer and nonamer recombinational signal sequence-specific DNA-binding protein(s) was examined in the nuclear extracts from lymphoid and nonlymphoid cell lines. Nuclear extracts were subjected to SDS-polyacrylamide gel electrophoresis, and transferred by electroblotting to nitrocellulose filters. Then the filters were hybridized to 32P-labelled synthetic double-stranded heptamer-23bp-nonamer or nonamer-12bp-heptamer recombinational signal sequence probes. A relatively large amount of a DNA-binding protein(s) of Mr 115,000 for both probes was detected in the nuclear extracts from immature B and immature T cell lines. No DNA-binding proteins were detected in a myeloma cell line. Interestingly, this DNA-binding protein(s) might be able to recognize both heptamer and nonamer. Recombinational signal sequence-specific DNA-binding activity of the protein(s) and the presence of the protein(s) in a stage-specific manner strongly suggest that the protein(s) of Mr 115,000 detected here may play an important role in the recombination of Ig and TCR genes.
...
PMID:Identification of a recombinational signal sequence-specific DNA-binding protein(s) of Mr 115,000 in the nuclear extracts from immature lymphoid cell lines. 221 1

Guinea pig polymorphonuclear leukocytes (PMNs) possess two distinct types of Fc gamma receptor (Fc gamma R): Fc gamma 1/gamma 2R for both IgG1 and IgG2, and Fc gamma 2R for IgG2 alone. The Fc gamma 2R was previously shown to differ antigenically from homologous macrophage (M phi) Fc gamma 2R by the use of a monoclonal antibody to M phi Fc gamma 2R (VIIAI IgG1), though the Fc gamma 1/gamma 2R cross-reacts with a monoclonal antibody to homologous M phi Fc gamma 1/gamma 2R (VIA2 IgG1). Recently, we obtained a monoclonal antibody (MP-2) secreted by a hybridoma prepared by fusion of the splenic cells of mice immunized with guinea pig PMNs with a myeloma cell line. This antibody completely inhibited both the Fc gamma 2R-mediated rosette formation of PMNs with IgG2 antibody-sensitized sheep erythrocytes and the Fc gamma 2R-mediated binding of ovalbumin (OA)-complexed IgG2 antibody to PMNs. When the antigen of MP-2 was isolated by affinity chromatography with the antibody-Sepharose, it gave a single band with a molecular weight of 120,000 on SDS-PAGE. The number of antigen molecules per PMN was estimated to be 9 X 10(4) by measuring the binding of 125I-MP-2 Fab. This value was essentially the same as that obtained by measuring the binding of OA-complexed IgG2 antibody to the PMNs treated with the Fab' of VIA2 IgG1. These results strongly suggest that MP-2 is a monoclonal antibody to PMN Fc gamma 2R.
...
PMID:Characterization of the Fc receptor for IgG2 on guinea pig polymorphonuclear leukocytes by the use of a monoclonal antibody. 222 13

Production of porcine monoclonal antibodies for use in research and immunotherapy has been hampered by the lack of suitable fusion partners which promote high efficiencies of hybridoma out-growth and immunoglobulin synthesis. To overcome these obstacles, five heteromyeloma fusion partners (HM-1,2,3,4 and 5) were constructed by successively fusing porcine lymphocytes with murine myeloma cells or murine x bovine heteromyeloma cells. Following section of hypoxanthine/aminopterin/thymidine (HAT)-sensitive mutants, karyotypes, growth rates and surface phenotypes of the heteromyelomas were determined. Karyotyping revealed an increase in the mean number of chromosomes present in HM-1,4 and 5 cells. Peak doubling times of the parental and HM cells ranged between 12.2 and 17.4 h. Uisng flow microfluorimetry and monoclonal antibodies specific for class I/II major histocompatability antigens, it was determined that the surface phenotype of HM-1,2,3,4 and 5 resembled that of the parental murine X63 myeloma cells. HM 1,2,3,4 and 5 were evaluated for their abilities to serve as fusion partners. Highest percentages of hybrid outgrowth (37%) and immunoglobulin synthesis (52%) were observed when HM-1 was fused with procine lymphocytes. When cloned, percentage of outgrowth and immunoglobulin synthesis increased if HM-1 and HM-2 were used as fusion partners. Cryopreservation of HM-1 and HM-2 did not adversely affect their abilities to promote hybrid outgrowth or immunoglobulin synthesis. During the first week following fusion of porcine lymphocytes with heteromyelomas, murine thymocytes were found to be essential for survival of the nascent hybrids. To confirm that immunoglobulin secreted by hybridomas was of porcine and not murine or bovine origin, culture supernates were subjected to SDS gel electrophoresis, electroblotted and identified. using species-specific isotyping reagents. Two of four cell lines tested secreted porcine light chains and one of four cell lines secreted whole IgM molecules. This paper is the first to describe porcine heteromyelomas for use as fusion partners. Similar to findings of human and bovine studies, our data suggest that heteromyeloma fusion partners perform better than rodent myelomas for creating hybridomas synthesizing porcine immunoglobulin.
...
PMID:Characterization of heteromyeloma fusion partners which promote the outgrowth of porcine hybridomas. 226 87

Growth cartilage (GC) cells of young rabbits were cultured in vitro and their homogenates were injected into mice. Hybridomas were prepared by the cell fusion technique between the myeloma cells and the spleen cells of the immunized mice. Monoclonal antibodies (MoAbs) were produced by the hybridomas in the peritoneal cavities of the mice, and some of these, temporarily named MoAbs A, B, D, N, P, and S, were studied. The localization of the antigens of each of the MoAbs in the GC or adjacent resting cartilage (RC) was examined by indirect fluorescent antibody staining. The molecular weight of the antigens was examined by immunoblot staining after SDS-polyacrylamide gel electrophoresis. MoAb A and MoAb N stained RC cells and GC cells, except calcified GC. MoAb B stained the hypertrophic and calcified GC, and matrices in the RC and proliferating GC. MoAb D stained the calcified GC. MoAb P and MoAb S stained the RC cells and the matrices in the GC, intensively in the hypertrophic GC and perichondrium. The molecular weights of the antigens of MoAbs A, P, and S were 40-70 KD, 35-40 KD and 30 KD, respectively.
...
PMID:Production and characterization of monoclonal antibodies against rabbit growth cartilage. 227 43

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>