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)

We have studied the rearrangement status of the T cell receptor genes in 64 B lymphoid cell lines, and we found that, unlike the immunoglobulin heavy chain genes in T lymphocytes, T cell receptor beta and related gamma chain genes are almost always in germ-line configuration in B lymphoid cells. The only exception was a myeloma MOPC511 (IgA, chi) which contained all T cell receptor genes, beta 1, beta 2, gamma 1, gamma 2, gamma 3 and alpha, in rearranged configuration in both homologous chromosomes. This exception supports the concept that all immunoglobulin and T cell receptor genes exploit the same recombinase to build their complete variable regions. Obviously, in MOPC511 cells the regulation, which confers the tissue specificity i.e. T vs. B lymphocytes, has failed.
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PMID:Rearrangements of T cell receptor loci can be found only rarely in B lymphoid cells. 300 4

Monoclonal antibody (A9-84) against a hepatocellular carcinoma cell line (PLC/PRF-5) was produced by somatic cell fusion. The hybridoma clones were screened by a rapid solid-phase enzyme-linked binding assay. The target cells were cultured in 96-well Linbro plate and fixed by methanol for screening. The specificity of the antibody was studied by enzyme-linked binding assay and immunofluorescence methods. It shows that A9-84 do not respond to 8 different human cancer cell lines (4 liver cancer, 1 esophageal cancer, 1 stomach cancer, 1 multiple myeloma and 1 lymphoblast cell line) and the peripheral mononuclear cells of 91 normal subjects. A9-84 is the subtype of IgG3. It is capable of inhibiting the growth of cultured PLC/PRF/5 cells with or without complement.
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PMID:[Action of monoclonal antibody against a hepatocellular carcinoma cell line (PLC/PRF/5)]. 301 21

The spontaneous mutation rate of immunoglobulin genes expressed in myeloma cells is well above that of other genes expressed in these or in other cell types. The nature of such mutations in one myeloma cell line, MPC11, was explored at the molecular level. Included in this study were MPC11 variants representing 24 independent and spontaneous mutations affecting immunoglobulin secretion. Of the mutants studied, 19 had ceased immunoglobulin heavy chain (IgH) production (nonproducers), and 5 produced from as little as 1/1,000 to as much as 1/10 the amount of immunoglobulin produced by MPC11 (low producers). Only one of the MPC11 mutants (a nonproducer) showed no evidence of DNA rearrangement in or near the expressed IgH gene. The formerly expressed gamma 2b gene had been deleted in 18 of the 19 nonproducers. All of the low producers had undergone DNA rearrangement in or near the expressed IgH gene, and three of them produced immunoglobulin of a new heavy chain class. The cause for reduced heavy-chain synthesis in the low producers is not yet known. However, in several of these mutants, the defect appeared to be posttranscriptional. In these cell lines, steady-state IgH mRNA levels were much lower than in the parent cell line, while the heavy-chain gene transcription rate remained unchanged.
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PMID:DNA rearrangement causes a high rate of spontaneous mutation at the immunoglobulin heavy-chain locus of a mouse myeloma cell line. 302 46

A complete human gamma 1 heavy chain gene (HIG1) was transferred into mouse cells by protoplast fusion. The HIG1 gene was strongly expressed in mouse myeloma cells but not in mouse fibroblasts (L cells). Nuclear extracts from myeloma cells were injected into L cell transformants containing one copy of the HIG1 gene; this triggered accurate transcription of the HIG1 gene in the transformants. The induction of HIG1 gene expression by a myeloma nuclear factor (or factors) appeared to depend on the enhancers in the heavy chain gene. Nuclear proteins prepared from cells of the B lineage could induce the transcription of HIG1 gene in the L cell transformants, while those from the cells of non-B-lineage could not. The present study shows that positive regulatory trans-acting factors are involved in the activation of the immunoglobulin heavy chain gene through its enhancers and are contained only in cells of the B lineage.
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PMID:Trans-acting nuclear protein responsible for induction of rearranged human immunoglobulin heavy chain gene. 308 20

We present a patient with multiple myeloma and double (IgA kappa + IgG kappa) paraproteinaemia in the serum. Immunofluorescence analysis of bone marrow plasma cell with fluorochrome-conjugated goat antibodies specific for mu, delta, gamma or alpha immunoglobulin heavy chain and kappa or lambda light chains revealed the presence of a plasma cell clone synthesizing simultaneously gamma, alpha and kappa chains. A minority of plasma cells synthesized gamma or alpha chains separately. Moreover, in the patient's peripheral blood, a few cells with the morphology of lymphoplasmoblasts and simultaneously positive for gamma, alpha and kappa chains were also detected. These results indicate that in this patient, the neoplastic plasma cell clone was 'frozen' at the differentiative step of the switch from IgG to IgA synthesis.
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PMID:Double (IgA kappa + IgG kappa) paraproteinaemia in a single patient: immunofluorescence evidence for a common plasma cell clone 'frozen' at the switch phase. 309 55

Production of human monoclonal antibodies reactive to stomach cancer was attempted by the hybridoma technique using splenic lymphocytes from stomach cancer patients. The parental cells used were NS-1 mouse myeloma line and three human lines including RPMI-1788 6TGR, which was established in our laboratories. Ten mouse-human and two human-human (from the fusion with RPMI-1788 6TGR) hybridomas have been producing IgM antibody for over 18 months, and all the heterohybridomas yielded ascites when transplanted into nude mice. Four antibodies produced by the heterohybridomas were selected and analyzed. These 4 antibodies, 3F6, 4A10, 3H5 and 1F9, reacted predominantly to cytoplasmic antigens of stomach and other epithelial cancer lines. The reactivity against human tumors transplantable in nude mice showed that all antibodies but 3F6 were reactive with stomach and lung cancers. Smears prepared from normal and cancer tissues were also tested, and these 4 antibodies showed positive reactions not only to stomach cancer, but also to normal stomach and colon. The reactivity against fetal tissues demonstrated that 3H5 antibody was reactive with epithelium of the stomach, and 1F9 antibody was positive with epithelium of the respiratory tract and bile duct, but the other two were negative. Thus, the serological analysis showed that the antigens detected are not tumor-specific, but are differentiation antigens. Chromosome analysis of these 4 mouse-human hybridomas and another one, which seems to produce an antibody against keratin, showed that three retained human chromosome 14 on which immunoglobulin heavy chain (Ig H) gene is located, but two did not. Southern blot analysis, however, revealed that all 5 hybridomas had a human Ig H gene.
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PMID:Human monoclonal antibody reactive to stomach cancer produced by mouse-human hybridoma technique. 309 22

Complete immunoglobulin heavy chain (IgH) genes (gamma and mu) containing the intronic IgH enhancer and mutations in the upstream promoter region were constructed in vitro and introduced into murine J558L myeloma cells by protoplast fusion. S1-nuclease mapping experiments demonstrated that IgH gene expression was extremely sensitive to mutation in an upstream region containing the octanucleotide sequence ATGCAAAT. Significant IgH mRNA levels were detected in RNA from cells transfected with IgH gene constructs in which all upstream sequences on the 5' proximal side of this element were deleted. Similar results were obtained using the precise inverse of the IgH octamer, which is found in the upstream promoter region of immunoglobulin light chain genes. Deletion of the IgH octamer, or point mutation of adenine to guanine at position 6, resulted in the loss of correctly initiated IgH mRNA. A DNA binding factor from J558L nuclear extracts was identified that appeared to recognize the octamer on the basis of differential binding to homologous restriction fragments containing the various mutations and that bound preferentially with octamer DNA fragments derived from functional relative to nonfunctional IgH constructs. Collectively, these data suggest that the octamer element contains residues that are critical to accurate immunoglobulin gene transcription and that may serve as part of a recognition locus for nuclear factors important to B-cell-specific immunoglobulin expression.
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PMID:Mutational analysis of the immunoglobulin heavy chain promoter region. 309 86

A monoclonal antibody to human IgG was tested with myeloma proteins of the four IgG subclasses. When tested by immunofluorometric assay, enzyme-linked immunosorbent assay, hemagglutination and hemagglutination inhibition assays, the antibody reacted with IgG3 but not with the other three IgG subclasses. When tested by Ouchterlony assays in the presence of polyethylene glycol, the antibody formed lines with all four IgG proteins. The line with IgG3 was sharp and stable, but the lines with the other three IgG subclasses tended to blur with time and with the lower PEG concentrations. These findings show that Ouchterlony assays can reveal cross-reactions of a monoclonal antibody that can be missed by more sensitive assays.
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PMID:A monoclonal antibody may show cross-reactivities in Ouchterlony assays but not in other assays. 310 Jun 50

A conserved decanucleotide (ATGCAAATNA) is present 45-60 nucleotides upstream from the transcription startpoint in all immunoglobulin heavy chain promoters (VH promoters). We have introduced this decanucleotide (cd sequence) at a similar position into the upstream flanking sequence of the mouse Renin-1 gene. This gene is only transcribed in highly specialized tissues, and the fragment used here (-449 to +30 with respect to the main transcription startpoint) has little promoter activity in fibroblastic or myeloma cell lines, even if coupled to a functional enhancer. In contrast, after insertion of the decanucleotide, this fragment, while still inactive in non-lymphoid cells, becomes a potent promoter in B-cells when associated with SV40 or immunoglobulin heavy chain enhancer. In all respects, the engineered fragment behaves like an authentic VH promoter isolated in this laboratory, except that it is even more active in B-cells. Deletion experiments show that all renin sequences are dispensable for the activity of the chimaeric promoter, except probably for the renin TATA box which defines the precise transcription startpoint. We conclude that the decanucleotide is sufficient to activate a promoter in B-cells but not in non-B-cells, and therefore that no other element is needed to account for the B-cell specificity of the VH promoter. In addition, our results suggest that the lack of activity of the renin promoter in non cognate cells is not due to the binding of a repressor.
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PMID:The conserved decanucleotide from the immunoglobulin heavy chain promoter induces a very high transcriptional activity in B-cells when introduced into an heterologous promoter. 311 45

Subclasses of 176 IgG and 62 IgA myeloma proteins were determined by indirect ELISA with monoclonal antibodies, as well as by an immunoblotting technique (for monoclonal IgG) and by immunoelectrophoresis against the lectin jacalin (for IgA). The subclass distribution of monoclonal IgG did not reflect mean normal serum levels of the correspondent isotypes, with an over-representation of IgG1 and IgG4 and an under-representation of IgG2 and IgG3 in myeloma. Similarly, IgA2 myeloma were clearly under-represented.
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PMID:Subclass distribution of human myeloma proteins as determined with monoclonal antibodies. 312 77


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