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)

C-type particles secreted in vivo by MOPC-315 myeloma cells were characterized. These particles localize at a density of 1-16 g/ml in sucrose and possess a 60 to 70S RNA and an RNA-instructed DNA polymerase. Endogenous enzyme activity requires manganese and is inhibited by ribonuclease or by the omission of any of the deoxynucleoside triphosphates. The enzyme utilizes the virus 60 to 70S RNA as a template to synthesize DNA molecules which specifically hybridize to the homologous RNA.
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PMID:RNA-instructed DNA polymerase associated with C-type particles produced in vivo by murine myeloma cells. 6 43

Messenger RNAs for antibody heavy (gamma) and light (kappa) chains were isolated from the polysomes of an IgG-producing mouse myeloma cell line. Polysomes engaged in heavy or light chain synthesis were separated by immunoprecipitation using rabbit antibodies specific for the mouse IgG formed. The mRNAs obtained, more than 85% specifying IgG [Legler, M. & Cohen, E. P. (1976) Biochemistry 15, 4390-4399], were used as "probes" in hybridization experiments with sheared mouse liver DNA. To determine whether mRNAs for Ig heavy and light chains contained covalently bound transcripts of unique and reiterated DNA, hybrids were isolated with or without treatment with ribonuclease (RNase) prior to fractionation and the apparent rates of hybridization were compared. A monophasic C(o)t (DNA concentration x incubation time) curve with a C(0)t(1/2) of 4000 moles of nucleotide per liter x sec, corresponding to less than five hybridization sites per haploid genome, was obtained whether or not RNase was used in the isolation protocol. With a similar experimental design, the apparent hybridization rates of heterogeneous nuclear RNA from the same cell source were clearly different. The "stringency" of the reaction was reduced by incubating the hybridization mixtures at lower temperatures in a further attempt to detect a large class of repetitive sequences that would form hybrids with the IgG mRNA used, if such sequences were present. The results, however, were the same; i.e., the apparent rates of hybridization of mRNAs for mouse antibody gamma and kappa chains with sheared mouse liver DNA were essentially the same whether or not RNase was used in the isolation procedure. Reiteration of genes in mouse liver DNA for mouse IgG could not be detected.
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PMID:Hybridization properties of immunoglobulin mRNA: failure to detect covalently associated IgG mRNA transcripts of reiterated and unique mouse DNA. 26 11

Two commonly used brands of reagent strip (dipsticks) were evlauated for their sensitivity to Bence-Jones and seven other urinary proteins. Both brands showed significant differences in sensitivity to albumin, glycoprotein, ribonuclease and lysozyme; both were most sensitive to albumin and least sensitive to globulin. Furthermore, their comparative sensitivities to these proteins also differed markedly. These differences in sensitivity could lead to underestimation of protein content in urine specimens. Tests on urines from patients with multiple myeloma showed that a negative urinary dipstick test result did not rule out the presence of the disease.
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PMID:Sensitivity of in vitro diagnostic dipstick tests to urinary protein. 64 3

32P-labeled light chain messenger RNA was prepared from mouse MOPC 21 myeloma cells. The messenger RNA was hybridized to purified repetitive nuclear DNA and both the hybridized (repetitive 32P-RNA) and nonhybridized (nonrepetitive 32P-RNA) fractions were isolated. Only the nonhybridized RNA gave a T1 ribonuclease fingerprint showing oligonucleotides derived from the variable and constant regions of the light chain messenger RNA. In addition, this fingerprint showed oligonucleotides derived from the untranslated regions of the light chain messenger RNA. The nonrepetitive 32P-RNA was shown to rehybridize only with the unique fraction of total nuclear DNA. The rapidly hybridizing part of the unfractionated 32P-RNA preparation, therefore, is not a component of the light chain messenger RNA itself. Complementary DNA was prepared with reverse transcriptase using unlabeled light chain messenger RNA as template, and the transcripts were fractionated into various size classes. Complementary DNA molecules greater than 900 bases in length hybridized with both the initial messenger RNA and with the nonrepetitive 32P-RNA but failed to hybridize with excess purified repetitive 32P-RNA. The rapidly hybridizing component of the messenger RNA fraction, therefore, does not appear to be transcribed by reverse transcriptase. It is concluded that, under the experimental conditions used, the light chain messenger RNA hybridizes exclusively with unique DNA.
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PMID:Demonstration that a mouse immunoglobulin light chain messenger RNA hybridizes exclusively with unique DNA. 80 42

A mutant cell line (IF2) derived from the mouse myeloma MOPC 21 has been used for the isolation and sequence analysis of H-chain mRNA. The IF2 cells synthesise an H-chain of reduced size in which the CH1 homology region is missing. Sizing of the IF2 H-chain mRNA and wild-type H-chain mRNA revealed that the deletion is expressed at the mRNA level. The mutant H-chain mRNA sedimented at 16-S, enabling effective resolution from 18-S ribosomal RNA. In experiments using IF2 cells labelled with [32P]phosphate, the 16-S mRNA was purified by oligo(T)-cellulose chromatography. Polyacrylamide gel analysis of the poly(A)-containing fraction showed the presence of a single radioactive band. Comparison of the mobility of this band relative to markers of known molecular weight revealed that the molecule contained about 1600 nucleotides. Digestion of the 32-P-labelled mRNA with T1 ribonuclease and two-dimensional fractionation of the resulting oligonucleotides yielded a 'finger-print' suitable for a preliminary sequence analysis. By using the established amino acid sequence of the IF2 H-chain and a knowledge of the genetic code, 14 oligonucleotides were assigned within the constant region and four within the variable region of the IF2 H-chain. This sequence data accounts for 19.5% of the coding region. Several other oligonucleotides, which could not be assigned within the coding region but which occurred in approximately molar yield, have also been partially characterised. These oligonucleotides are presumably derived from the untranslated regions of mRNA.
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PMID:Purification and sequence analysis of the mRNA coding for an immunoglobulin heavy chain. 81 96

We have investigated the pathogenesis of the polyclonal hypogammaglobulinemia associated with BALB/c plasmacytomas TEPC-183 and SPQC-11 to gain insight into the hypogammaglobulinemia observed in human myeloma. With pokeweed mitogen-driven IgM biosynthesis by mouse splenocytes as the indicator system for suppression, we found that a protein extract of asscites cells obtained from these tumor-bearing animals could suppress immunoglobulin production, whereas like extracts from a non-suppressing plasmacytoma, modified RPC-5, caused no suppression in vitro. Extracts of tumor ascites depleted of mononuclear phagocytes by iron carbonyl treatment showed little suppressor activity. The active extract was not cytotoxic and contained no mycoplasma or common murine viruses. Furthermore, the active suppressor factor appears to be a low m.w. protein that is not affected by treatment with ribonuclease. These results and others are consistent with the idea that the hypogammaglobulinemia of myeloma is due to the formation of immunoregulatory macrophage-like cells which synthesize a suppressor substance.
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PMID:Hypogammaglobulinemia in experimental myeloma: the role of suppressor factors from mononuclear phagocytes. 85 68

The usefulness of plasma ribonuclease assays was studied in (i) patients with possible protein deficiency, (ii) patients with myelomatosis, (iii) patients with carcinoma of the breast. In each group, the major factor associated with elevation of plasma ribonuclease was impairment of renal function. The assay was therefore of little value in the assessment of patients with myelomatosis or carcinoma of the breast. However, in the patients with possible protein deficiency and normal renal function, an elevation of plasma ribonuclease is, in general, associated with a decrease in serum albumin, transferrin and cholinesterase. Plasma ribonuclease may therefore be a useful parameter in the assessment of protein nutritional status.
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PMID:An assessment of the clinical usefulness of plasma ribonuclease assays. 97 78

Infusion of cycloheximide i.v., an antibiotic known to inhibit synthesis of protein, at a rate of 0.2 mg/kg/hr, reliably caused lysis of fever in 15 chronically febrile patients with Hodgkin's disease who did not have detectable bacterial, fungal, or viral infection. Antipyretic effects were also seen in some patients with reticulum cell sarcoma, lymphosarcoma, acute leukemia, histiocytic medullary reticulosis, plasma cell myeloma, carcinoma of the lung, and carcinoma of the cervix. The drug failed to produce defervescence in four patients with normal granulocyte reserves, who were febrile due to bacterial infection. When infused at a rate of 0.2 mg/kg/hr, the drug apparently caused an acute alteration of protein metabolism in man in that plasma amino acid nitrogen rose acutely while plasma levels of muramidase and ribonuclease fell during the period of the infusion. The data suggest that continuing synthesis of protein may be involved in nonbacterial fever of neoplastic disease. Mammalian granulocytes and monocytes are known to elaborate a pyrogenic protein following appropriate stimulation; it is suggested that in some types of neoplastic disease, particularly Hodgkin's disease, tumor cells may produce and release a pyrogenic protein and that drug-induced inhibition of its synthesis is responsible for the observed lysis of fever.
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PMID:Antipyretic effect of cycloheximide, and inhibitor of protein synthesis, in patients with Hodgkin's disease or other malignant neoplasms. 109 49

Nuclei of MPC 11 mouse myeloma cells contain several species of small RNAs related to those found in other mammalian cells. These include U1 RNA, about 190 nucleotides in length and U2 RNA, about 170 nucleotides long. The 5'-termini of 32P-labelled U1 and U2 RNAs have been investigated by a fingerprinting technique involving digestion with T2-ribonuclease. The RNAs were found to have modified 5'-terminal structures of the form m3G(5')ppp (5')AmpUmpAp for U1 RNA and m3G(5')ppp(5')AmpUmpCmpCp for U2 RNA, where m3G is N2, N27-trimethyl guanosine and Am and Um are 2'-O-methyl nucleosides. These 5'-terminal sequences are the same as those proposed for rat hepatoma U1 and U2 RNAs (Ro-Choi et al., Fed. Proc. 33, 1548, 1974) but with triphosphate rather than diphosphate links.
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PMID:Modified 5'-termini in small nuclear RNAs of mouse myeloma cells. 121 81

Recent evidence suggests that tumour necrosis factor alpha (TNF) is an autocrine growth factor for the chronic B-cell malignancies hairy cell leukaemia (HCL) and some cases of B-chronic lymphocytic leukaemia (B-CLL). Incubation with TNF in vitro has been shown to increase viability, DNA synthesis and the expression of the protooncogenes myc, fos and jun in the tumour cells from these patients. TNF in vitro also increases expression of TNF-mRNA, suggesting the existence of an autocrine growth loop for TNF in these cells. Current experiments are compatible with the hypothesis that interferon alpha (IFN) interferes with this autocrine growth loop in HCL and B-CLL by stimulating degradation of messenger RNAs (mRNAs) for a number of cytokines including that of TNF. This RNA degradation may be mediated through induction of the enzyme 2,5 oligo-A synthetase with consequent increased synthesis of 2,5 oligo-A which is known to stimulate the activity of a latent ribonuclease capable of degrading cytokine mRNAs. Circulating tumour-derived TNF may also contribute to the pancytopenia in HCL and B-CLL. Whether cytokine autocrine growth loops are important in other B-cell malignancies, e.g. myeloma and non-Hodgkin's lymphoma, and subject to IFN-stimulated breakdown needs further study.
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PMID:Possible mechanism of action of interferon alpha in chronic B-cell malignancies. 193 2


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