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)

UV irradiation of infectious vesicular stomatitis virus was employed to study the relationship between the expression of certain viral gene functions and viral inhibition of RNA synthesis in mouse myeloma (MPC-11) cells. Viral infectivity, protein synthesis, and viral mRNA synthesis were all highly susceptible to inactivation by UV radiation; however, low levels of viral transcriptase activity were detected in vitro in virus preparations subjected to large doses of UV radiation. In sharp contrast, the capacity of vesicular stomatitis virus to shut off cellular transcription was quite resistant to UV radiation. The data presented here indicate that viral transcription is essential to inhibit host RNA metabolism, even though synthesis of viral polypeptides in the inhibited cells could not be detected. At those levels of UV radiation that inactivated all viral gene functions, except viral inhibition of cellular RNA synthesis, the only viral product detected was non-adenylated, low-molecular-weight RNA species.
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PMID:Use of UV irradiation to identify the genetic information of vesicular stomatitis virus responsible for shutting off cellular RNA synthesis. 9 Jan 65

Using cultured mouse myeloma cells, it has been possible to derive cells which are now synthesizing products similar to human heavy chain disease proteins. An initial mutant was isolated which snythesized a heavy chain with an internal deletion and a normal light chain. In a subsequent step, a variant was identified in which the synthesis of the heavy chain with the deletion persisted in the absence of light chain synthesis. These experiments also demonstrate that in the MPC-11-derived cultured cell line, the continued synthesis of heavy chain does not require the synthesis of light chain.
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PMID:Murine heavy chain disease. 9 58

The nuclear precursors of the immunoglobulin messenger RNAs of MPC-11 cells were characterized with respect to size, amount per cell and extent of polyadenylation. These cells produce three Ig mRNAs: a 1.8 kb component coding for a gamma2b heavy chain (H mRNA), a 1.2 kb mRNA coding for a k light chain (L mRNA) and a 0.8 kb mRNA coding for the constant region portion of the k light chain (Lf mRNA). To identify the pre-mRNAs without ambiguity, we constructed recombinant DNA plasmids containing H and L cDNA sequences, and used the cloned cDNAs as hybridization probes for analysis of steady state nuclear RNA and in DNA excess hybridization experiments with pulse-labeled nuclear RNA. The nuclear molecules containing Ig sequences consist of an 11 kb component (H1), which we believe to be the primary transcript of the H gene, 5.3 kb (L1), and 3.3 kb (L2) components, which seem to be primary transcripts of the L and L1 genes, components corresponding to mature size H, L and Lf mRNAs, and several intermediate-sized components which include the processing derivatives. The precursor role of these nuclear molecules was established by studies of their labeling kinetics and by appropriate pulse-chase experiments. All the pre-mRNA species including H1, L1 and L2 contain poly(A), thus suggesting that polyadenylation is an early event in the processing of these mRNAs. The MPC-11 cell contains about 30,000 and 40,000 cytoplasmic H and L mRNA molecules, respectively, which must be produced within one cell generation (approximately 24 hr). In comparison, the nucleus contains about 100-150 molecules of total pre-mRNA and only about 10-15 molecules of presumptive primary transcripts for each of these Ig species. These values indicate very rapid transcription rates (greater than 20 transcripts per min) and exceptionally fast processing rates (approximately 0.5 min for the primary transcripts and approximately 5 min for overall nuclear processing) for the Ig mRNAs. Thus rapid transcription and processing, together with high cytoplasmic stability, account for the high abundance of Ig mRNAs in the myeloma cell.
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PMID:The synthesis and processing of the messenger RNAs specifying heavy and light chain immunoglobulins in MPC-11 cells. 10 31

The initial step of intermolecular covalent assembly of immunoglobulins molecules involves formation of heavy chain-light chain or heavy chain-heavy chain disulfide bonds. Using QAE-Sephadex chromatography to isolate microsomal nascent polypeptides, we have shown that this initial step of intermolecular covalent assembly occurs, to a substantial extent, on nascent heavy chains, as well as on completed heavy chains as previously demonstrated by others. In MPC 11 mouse myeloma cells, completed light chains are assembled covalently to nascent heavy chains, whereas in MOPC 21 mouse myeloma cells, completed heavy chains are assembled covalently to nascent heavy chains. These results are consisted with the heavy-light half-molecule being the major initial intermediate in the assembly of MPC 11 IgG2b and heavy-heavy dimer being the major initial intermediate formed in assembly of MOPC 21 IgG1. The nascent MPC 11 heavy chain must be at least 38,000 daltons in size before assembly with the light chain occurs, even though the heavy chain cysteine involved in this disulfide bond is 131 residues (approximately 15,000 daltons) from the NH2 terminus. In addition, pulse-chase labeling studies of MPC 11 cells have shown that the assembly of completed light chains with the nascent heavy chain must occur within a few minutes of the synthesis of the light chain even though a large excess of unassembled MPC 11 light chains remain inside the cell for an average time of 2 h before being secreted.
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PMID:Formation of intermolecular disulfide bonds on nascent immunoglobulin polypeptides. 10 40

A spontaneous assembly variant, B 50, has been isolated from the MPC-11 mouse myeloma cell line. This variant synthesizes fewer light chains per cell than the parent resulting the production of a slight molar excess of heavy chains. These changes are associated with a delay and change in the pathway of assembly and a delay in secretion. Spontaneous revertants of B 50 have been obtained, all of which synthesize normal amounts of light chains and assemble and secrete the immunoglobulin molecule through the same pathways and with the same kinetics as the parental cells. A comparison of the tryptic-chymotryptic peptides of the parental, variant and revertant heavy and light chains did not reveal any differences. These studies indicate that variants in mouse myeloma cells can arise with defects in the quantitative expression of the immunoglobulin gene and suggest that the presence of excess light chains facilitates the assembly and secretion of some immunoglobulin molecules.
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PMID:A mouse myeloma variant with a defect in light chain synthesis. 11 96

DNA from newborn mice was digested with restriction endonuclease EcoRI, and a 6.6-kilobase fragment encoding immunoglobulin gamma 2b chain mRNA derived from MPC 11 myeloma was enriched about 100-fold by RPC-5 column chromatography and agarose gell electrophoresis. The 6.6-kilobase fragment was cloned with lambda gt WES.lambda B as EK2 vector. The cloned phage (lambda WES.IgH22) contained the constant region gene of the gamma 2b chain but not the variable region gene of MPC 11 mRNA. The constant region genes of the other gamma chains (i.e., gamma 1, gamma 2a, and gamma 3) were not present in lambda gt WES.IgH22 DNA. R-loop mapping indicates that the gamma 2b chain structural gene is divided into two parts (330 +/- 60 SD base pairs and 930 +/- 110 SD base pairs) by an intervening sequence (360 +/- 100 SD base pairs). The nucleotide sequence around the junction of the hinge region and CH2 domain was determined and shown to match the amino acid sequence of the initial part of the CH2 domain of the gamma 2b chain. The base sequence upstream from the junction, however, is unrelated to the amino acid sequence of the CH1 domain and the hinge region of all the gamma chains whose sequences have been determined. These results indicate that the gamma 2b chain gene is interrupted at the junction of the hinge region and CH2 domain by an intervening sequence. The existence of two more intervening sequences, one between the CH1 domain and the hinge region and the other between the CH2 and CH3 domains, is discussed.
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PMID:Cloning immunoglobulin gamma 2b chain gene of mouse: characterization and partial sequence determination. 11 31

Infection of mouse myeloma cells (MPC-11) with vesicular stomatitis (VS) virus resulted in rapid and marked reduction in cellular RNA synthesis considerably before cell viability was compromised. Mouse myeloma cells responded maximally to viral infection at a multiplicity of 1 and were considerably more se;sitive to shut-off of RNA synthesis than were mouse L cells or BHK-21 cells. This inhibition of cellular RNA synthesis was shown not to be caused by differential membrane permeability of infected and uninfected MPC-11 cells to [3H]uridine, nor was it due to greater degradation of previously synthesized RNA. VS viral infection appeared not to impede transport of newly synthesized nuclear RNA to the cytoplasm; moreover, infected cells accumulated polyadenylated mRNA at the same rate as did uninfected cells. Polyacrylamide gel electrophoresis of newly synthesized nuclear RNA demonstrated that the polydisperse nature and size distribution were not affected by VS viral infection. Isolated nuclei of infected MPC-11 cells also inhibited greatly impaired capacity to synthesize RNA despite the absence of cytoplasmic factors. Infected-cell cytosol did not inhibit transcription by uninfected-cell nuclei, nor did uninfected-cell cytosol reverse viral inhibition of nuclear transcription. Studies with alpha-amanitin revealed that VS viral infection inhibited the activity of polymerases I, II, and III, but only polymerase II was affected progressively throughout infection and to a much greater extent. These data suggest that, even at low multiplicities of infection, VS virus rapidly shuts off cellular RNA synthesis at the level of nuclear transcription.
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PMID:Inhibition of RNA synthesis in mouse myeloma cells infected with vesicular stomatitis virus. 20 71

Infection of mouse myeloma (MPC-11) cells with vesicular stomatitis virus resulted in rapid loss in activity of cellular RNA polymerases associated with nuclear chromatin. No RNA polymerase inhibitor could be detected in extracts of infected cell nuclei. Reconstitution experiments with solubilized RNA polymerases dissociated from chromatin of infected and uninfected cells demonstrated that vesicular stomatitis viral infection did not affect the ability of the polymerases to function on endogenous or exogenous templates; nor did infection alter the template capability of the chromatin. Measurement of the number of actively growing RNA chains revealed that infected cell nuclei contained fewer active polymerase units; however, the rates of RNA chain elongation were the same in nuclei from infected and uninfected cells. Quantitation of the number of polymerase units active in nuclear chromatin revealed that the alpha-amantin-sensitive polymerase II was more severely reduced by viral infection than were polymerases I and III.
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PMID:Vesicular stomatitis virus infection reduces the number of active DNA-dependent RNA polymerases in myeloma cells. 22 70

RNA synthesis by mouse myeloma (MPC-11) cells was rapidly and progressively shut off by infection with vesicular stomatitis virus temperature-sensitive (ts) mutants permissive for transcription. In sharp contrast, mutants or defective vesicular stomatitis virions restricted in transcription were incapable of causing progressive inhibition of cellular RNA synthesis even at massive multiplicities of infection. A viral product synthesized 30 to 60 min after permissive infection with tsG114(I) appeared to be essential for prolonged inhibition of RNA synthesis in cells switched up to restrictive temperature.
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PMID:Transcription of vesicular stomatitis virus is required to shut off cellular RNA synthesis. 22 26

We describe a procedure for the isolation of somatic cell variants in which gene products are expressed on the cell surface that are not expressed in the wild type. Cloned cells of the myeloma line MPC 11, which expresses an IgG2b protein, were incubated with an antiserum specific for IgGI and IgG2a. Cells reacting with this antiserum were stained with a fluorescent anti-antiserum and enriched in three cycles of sorting in the fluorescence-activated cell sorter and subsequent growth in vitro. From the enriched population two variants were isolated by cloning in soft agar. One of them expressed a variant immunoglobulin that types serologically as an IgG2a but whose variable portion was idiotypically related to that of the MPC 11 wild-type protein.
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PMID:Isolation of myeloma variants with predefined variant surface immunoglobulin by cell sorting. 30 57


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