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)

During differentiation, B lymphocytes undergo a shift from expression of membrane-bound IgM to IgM secretion. The mu chains of membrane and secreted IgM, mum and mus, respectively, differ in the amino acid sequence of their carboxy terminal regions. In this paper, we demonstrate that mum and mus heavy chains are encoded by separate mRNAs of 2.7 and 2.4 kb, respectively. Restriction mapping and sequence analysis of mu cDNA clones from a myeloma tumor that produces both types of mu chain indicate that the mum and mus mRNAs are identical throughout the coding region up to the 3' end of the fourth constant region (Cmu 4) domain, but differ in their C terminal coding and 3' untranslated segments. From the nucleotide sequence of the mum cDNA clone, we predict the amino acid sequence of the 41-residue mum C terminal segment or "M" (membrane) segment. This sequence has characteristics consistent with its being a transmembrane peptide. Thus the mus chain has a 20-residue hydrophilic C terminal segment after the Cmu 4 domain, and the mum chain has a 41-residue C terminal segment containing a hydrophobic sequence. We propose that comparable C terminal segments also will be found in other membrane-bound immunoglobulin heavy chains.
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PMID:Two mRNAs with different 3' ends encode membrane-bound and secreted forms of immunoglobulin mu chain. 677 Oct 19

We have analyzed the sequence complexity, frequency distribution, and template activity of free (F) and membrane-bound (MB) polysomal mRNA populations of MOPC 21 (P3K) mouse myeloma cells. Using the technique of mRNA-cDNA hybridization, we find that F poly(A)+ RNA, which represent 60% of total polysomal mRNA, consists of approximately 8,000 different mRNA sequences distributed in three abundance classes, while MB poly(A)+ RNA (20% of total polysomal mRNA) includes only 230 mRNA species and almost completely lacks very infrequent mRNA species. Cross-hybridization indicates that MB mRNA sequences are also present in F mRNA, but in reduced concentrations. Translation of F and MB RNA fractions in a messenger-dependent reticulocyte lysate indicates that essentially all MB RNA contains poly(A), whereas 25% of F mRNA lacks poly(A). Furthermore, the use of a cDNA highly specific for the immunoglobulin light (Ig L) chain mRNA allows the determination of the subcellular content of this message. Ig L mRNA, representing approximately 5% of total polysomal poly(A)+ RNA, is one of the most abundant MB mRNAs. 90% of Ig L mRNA is found in MB polysomes and 10% in F polysomes.
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PMID:Membrane-bound ribosomes of myeloma cells. IV. mRNA complexity of free and membrane-bound polysomes. 678 9

The subcellular distribution of the most abundant mRNA sequences, particularly those of the immunoglobulin heavy (Ig H) and light (IG L) chain mRNA sequences, of MOPC 21 (P3K) mouse myeloma cells has been examined by translating the mRNA of various subcellular fractions in a messenger-dependent reticulocyte lysate (MDL) and by identifying Ig products with the use of a specific antiserum. Analyses of the distribution of the mRNA template activity and the translation products by SDS polyacrylamide gel electrophoresis reveal that approximately 85% of the mRNA present in the free ribosomal fraction is incorporated into polysomes and that the remainder is present as mRNP particles. On the endoplasmic reticulum (ER) the mRNA is found entirely in polysomes. In general, the size class of free (F) and membrane-bound (MB) polysomes corresponds to the size of their translation products. Thus, mRNAs coding Ig H (5.0 x 10(5) daltons in size) and Ig L (2.5 x 10(5) daltons in size) are incorporated into polysomes formed of 12 and 6 ribosomes, respectively. About 10% of the Ig mRNAs are not bound to membranes. A third of these are associated with mRNPs and the remainder incorporated into F polysomes of the same size as the Ig-synthesizing MB polysomes.
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PMID:Membrane-bound ribosomes of myeloma cells. V. Subcellular distribution of immunoglobulin mRNA molecules. 678 10

Immunoglobulin heavy (Ig H) and light (Ig L) chain mRNA molecules have been released from the endoplasmic reticulum (ER) membranes as free (F) mRNP particles when MOPC 21 (P3K) mouse myeloma cells are exposed to a hypertonic initiation block (HIB). The subsequent fate of these mRNA sequences has been examined when the cells are returned to normal growth medium. Upon return to isotonicity, all previously translated mRNA molecules reassociate with ribosomes and form functional polysomes. Ig H mRNA is found incorporated first into F polysomes and then into membrane-bound (MB) polysomes. Kinetic studies indicate that the time of passage of Ig H mRNA in F polysomes is approximately 30 s, during which a nascent polypeptide chain of approximately 80 amino acids would have been completed. When the rate of polypeptide elongation is depressed with emetine during the recovery from HIB, both Ig H and L mRNA molecules accumulate in small F polysomes. These results indicate that the formation of Ig-synthesizing polysomes proceeds in the sequence: mRNA leads to F polysomes leads to MB polysomes. With the additional observation that during HIB recovery puromycin completely prevents the reassociation of Ig mRNA with the ER, these findings support a model of MB polysome formation in which the specificity of membrane attachment is determined by the nature of the N-terminal amino acid sequence of the nascent polypeptide chain.
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PMID:Membrane-bound ribosomes of myeloma cells. VI. Initiation of immunoglobulin mRNA translation occurs on free ribosomes. 678 11

We prepared ultra-thin sections of human myeloma cells, in which the rER was cut tangentially, and studied the make-up and distribution of membrane-bound polysomes electromicroscopically. In IgG myeloma large and small polysomes were detected. The polysome distribution curve showed a high peak at 7 ribosomes and a lower peak at 17-18 ribosomes. IgA-, IgD- and IgE myeloma, as well as macroglobulinemia, showed peaks at 7 and 13 ribosomes. BJP myeloma manifested a sharp peak only at 7 ribosomes. Our results suggest that BJP myeloma has only small polysomes participating in L-chain synthesis, while the other myelomas exhibited large and small polysomes participating in H- and L-chain synthesis, respectively. The quantitative ratio of small and large polysomes was determined on the basis of an analytically corrected direct count.
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PMID:Ultrastructural analysis of membrane-bound polysomes in human myeloma cells. 680 Apr 25

We have determined the amino acid sequence of the variable (V) region of the delta heavy (H) chain of human IgD isolated from the plasma of myeloma patient WAH. This V region is unusual in its amino end group (arginine) and in its length (129 residues). The length is due to 10 insertions in the third complementarity-determining region (CDR3). A computer search showed that no reported CDR3-joining region (-JH) sequences are identical and that they appear to be unrelated to the constant (C) region sequences of immunoglobulins. The V region sequence together with our previous results for the C region give the complete sequence of the human delta chain WAH, which has 512 amino acid residues and a Mr congruent to 65,000. The human delta chain has four domains (V, C delta 1, C delta 2, and C delta 3) and a long hinge region; by comparison, the mouse delta chain lacks a continuous segment of 135 residues, including half the hinge region and the entire C delta 2 domain. The human and mouse delta chains also differ in the number, kind, and location of GlcN and GalN glycans and probably in conformation and quaternary structure. These and other considerations suggest that there may be multiple forms of both secreted and membrane-bound IgD that differ in size, structure, and function.
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PMID:Complete amino acid sequence of the delta heavy chain of human immunoglobulin D. 680 18

Using our electron microscopic method of polysome analysis we ascertained the numbers of membrane-bound polysomes and their constituent ribosomes in myeloma cells of J 606 (IgG3) and MOPC315 (IgA) parent cell lines and in their variants that did not produce and, accordingly, secrete either H- or L-chains. Both variants had far fewer membrane-bound polysomes than the respective parent lines. The polysome distribution curve drawn for each of these variants showed one peak at 5-6 ribosomes. In contrast to this finding, the distribution curves for the J 606 and MOPC315 parent lines gave two peaks. These observations on mouse myelomas strongly resembled those on human myelomas.
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PMID:Ultrastructural analysis of membrane-bound polysomes in mouse "nonsecretory" myeloma (nonproducing type). 688 30

The murine myeloma MOPC-315 secretes a paraprotein which binds dinitrophenylated compounds. Maturational subsets which mimic normal B-cell differentiation were shown to exist within this monoclonal neoplasm. The maturational subsets were defined by an in vivo stem cell activity (plasmacytoma colony-forming unit-spleen), DNA synthesis ([3H]thymidine incorporation), membrane-bound paraprotein, and cells secreting the MOPC-315 paraprotein. Velocity sedimentation at unit gravity separated cells enriched for secreting the MOPC0-315 protein (14.6 mm/hr) from the plasmacytoma colony-forming unit-spleen enriched population (9.3 mm/hr). An in vivo sequential analysis of the appearance of tumor (i.v. challenge) in the spleen of BALB/c hosts did not reveal any discordant appearance of these same maturational subsets with respect to time. The MOPC-315 myeloma contains maturational subsets that mimic normal B-cell differentiation and apparently differentiates during a very early stage of its evolution within the host.
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PMID:Intratumor maturational heterogeneity within the murine myeloma MOPC-315. 696 29

Using our electron microscopic method for polysome analysis and an immunofluorescent technique we studied Ig production and secretion by tumor cells in seven BJP myeloma patients and seven "nonsecretory" myeloma patients. In BJP myeloma Ig production and secretion is of three types: Type 1, only L-chains are synthesized and secreted; Type 2, the myeloma cells show fluorescence for H-chains, but upon polysome analysis there is no peak at polysomes corresponding H-chain production; Type 3, the myeloma cells show fluorescence for H-chains, and polysome analysis shows two peaks corresponding to L- and H-chain production. Polysome analysis of "nonsecretory myelomas show the presence of only very few membrane-bound polysomes and their distribution curves are entirely different from those of "ordinary" myeloma. Furthermore, the distribution patterns vary among seven cases. Results obtained by polysome analysis and immunofluorescent technique suggest that the "nonsecretory" myeloma could be divided into several subtypes.
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PMID:Immunoglobulin production and secretion in Bence Jones protein myeloma and "nonsecretory" myeloma. Ultrastructural and immunofluorescence study. 704 67

In vitro cultured mouse myeloma (Sp-2/0-Ag14) cells and phosphatidylcholine liposomes were used to study the membrane effects of photosensitization with an He-Ne laser activated haematoporphyrin (HP). Lipophilic HP molecules, intercalated between the membrane lipid molecules, caused morphological changes of cell membranes on light activation. Steady state and time-resolved fluorescence spectroscopic studies of membrane-bound HP molecules provide information about the change in membrane lipid dynamics (fluidity). Increased HP fluorescence anisotropy was found after laser irradiation in the case of cell membrane. This finding can be related either to the increased rotation correlation time of the rotating fluorophore (HP) (decreased membrane fluidity) or to the decrease in the angular range of molecular rotation, which corresponds to an increased lipid order after photosensitization. Changes in the ratio of saturated:unsaturated fatty acid content of membrane lipids or other chemical events such as cross-linking of membrane components during the photosensitization process can also account for the observed effects.
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PMID:Effect of haematoporphyrin-induced photosensitization on lipid membranes. 747 12


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