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)

A case of multiple myeloma with no monoclonal protein synthesis is reported. The patient had hypogammaglobulinemia, bone marrow invasion, osteolytic lesions, and plasma cell tumors. The absence of protein synthesis has been demonstrated in bone marrow culture with tritiated leucine. No evidence of immunoglobulin production was found. Bone marrow or plasma cell tumor biopsy may be the only method of diagnosis in such cases.
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PMID:Nonsynthetizing multiple myeloma. 61 90

Several human myeloma cell populations were studied using a combination of cytochemical (Unna-Pappenheim and naphthol yellow staining, Feulgen reaction) and autoradiographical (uridine, leucine, thymidine uptake and actinomycin binding) techniques. Progressive differentiation of the myeloma population was associated with: 1. a loss of proliferative activity, 2. decreased transcriptional capacity, 3. decreased RNA and protein synthesis, 4. increased RNA and protein concentrations, 5. greater stability of the protein synthesis template. The existence of a pre-myelomatous compartment is suggested in the light of these results and those of previous kinetic studies in vivo.
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PMID:Biology of the human myeloma cell population. I.Macromolecular characteristics. 70 77

A kinetic study of five human myeloma cell populations before and after chemotherapy using cytochemical and autoradiographical techniques showed: 1. a large number of cells, with a DNA content intermediate between 2c and 4c, that did not incorporate thymidine ('U' cells) and were indicative of ineffective myelomapoiesis; 2. non cell cycle-specific (cyclophosphamide) followed by cell cycle-specific (vincristine) treatment led to an increase in the 3H-thymidine labelling index (LI) and activation of macromolecular synthesis (increased uridine and leucine uptake and actinomycin binding capacity) pointing to early cell recruitment. A high percentage of 'U' cells can be found even after therapy. The LI variations make it clear that recruitment after therapy is overestimated by at least 40% due to ineffective myelomapoiesis. In the light of this and previous personal studies, we propose a kinetic pattern: the myeloma population may be seen as a highly differentiating population whose non-proliferating cells cannot re-enter the cycle. By contrast, the acute leukemia populations are unable to differentiate, and the non-proliferating cells (G0) can be recalled into the cell cycle.
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PMID:Biology of the human myeloma cell population. II. Cytokinetic characteristics. 70 78

The digestion of a human IgG1 K myeloma protein with pepsin in the presence of 8M-urea was observed to produce a fragment, designated Fb'2, which differed from the products of aqueous peptic digestion and from other characteristic immunoglobulin digestion products. 2. Fragment Fb's was also found when two other IgG1/K proteins were treated similarly. 3. Sedimentation-equilibrium studies showed the mol.wt. of fragment Fb'2 to be 56800. 4. On reduction, two equivalents of each of three peptides were released from fragment Fb's; these were characterized by N- and C-terminal determinations and by amino acid sequencing. 5. Fragment Fb'2 was shown to consist of the constant regions of both light chains, from residue Ile-117 to the C-terminus, and the CH1 domains and hinge region of the heavy chains, from residue Val-113 to residue Met-252, with a gap of five residues within the intrachain disulphide loop, between residues Leu-174 and Tyr-180.
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PMID:Fb'2, a new peptic fragment of human immunoglobulin G. 77 69

Bone marrow cells from two patients without detectable monoclonal immunoglobulin (Ig) in serum and urine but with the clinical picture of plasma cell myeloma were cultivated in vitro. Immunofluorescence studies of cultured living and fixed bone marrow cells showed no signs of Ig production in one of the cases, whereas in the other case cytoplasmic kappa chains were detected, which, however, were not expressed at the surface of living cells. Cells from the later patient were also subjected to kinetic, ultrastructural, and functional studies in vitro. The fraction of myeloma cells incorporating tritiated thymidine in vitro decreased gradually during prolonged culture, indicating a continuous cell death. The morphological characterization revealed many similarities between this nonsecretory myeloma and classical myeloma, although the frequency of cells with cisternae of endoplasmic reticulum distended by a granular material was unusually high, as was the frequency of "flaming" myeloma cells. "Flaming" cells were not labeled by tritiated thymidine, suggesting that they are nonproliferative end cells. Studies of the Ig synthesis by gel diffusion analyses of supernatant and cell lysates from [14C]leucine-labeled cultures agreed with the immunofluorescence studies that the myeloma cells were nonsecretory.
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PMID:Short-term tissue culture of two nonsecretory human myelomas. A morphological and functional study. 79 May 40

The digestion of human IgG1/K myeloma proteins with pepsin in the presence of 8 M-urea produces fragments that differ from those produced by aqueous peptic digestion, and from other characteristic immunoglobulin fragments. Fb'2, the larger urea/pepsin fragment, was previously shown to consist of the constant regions of the light chains, and the CH1 domains and hinge regions of the heavy chains. The smaller fragment, upFc, has now been characterized. After reduction, three peptides were released from fragment upFc. Amino acid sequencing, N- and C-terminal determinations and amino acid compositions have enabled these peptides to be identified as residues Ile-253 to Leu-306, residues Thr-307 to Asp-376 and residues Thr-411 to Gly-446 of the heavy chain. Fragment upFc therefore contains the entire Fc region, beginning at residue Ile-253, except for a 34-residue section from within the CH3-domain disulphide loop. Peptic digestion of IgG1/K proteins in 8M-urea therefore provides a method for isolating from gamma1 heavy chains five homogeneous peptides in good yield, which account for almost the entire constant region. Characterization of fragments Fb'2 and upFc has shown that the action of pepsin in urea is entirely different from that of aqueous pepsin. Two gamma1 heavy chains have been shown to differ in sequence at three positions from the sequence reported for protein Eu.
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PMID:Characterization of upFc, a fragment of human immunoglobulin G1 produced by pepsin in urea. 79 Dec 67

Mouse myeloma tumors and some variants derived from them were labeled in vitro with tritiated leucine and the radioactive J chain was assayed in cell lysates by precipitation with an antiserum specific for mouse J chain. The major findings were: 1) J chain can be found in an IgG2b-secreting cells (MPC-11). These data, together with previous findings suggest that cells secreting all classes of IgG synthesize J chain, even though there is no apparent requirement for J chain in assembly of the IgG molecule. Hence production of J chain does not depend upon secretion of a polymeric immunoglobulin. 2) Intracellular J chain can be found in myeloma variants that do not produce heavy chains showing that production of J chain may not coordinately be linked to the synthesis of heavy chain. 3) J chain was found in cells synthesizing, but not secreting, immunoglobulin. Thus production of J chain is not linked to secretion of immunoglobulin. 4) J chain could not be detected in plasma cells that do not produce immunoglobulins. It was also not found in mouse leukemic cells, suggesting that production of J chain is probably linked in some way to immunoglobulin production.
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PMID:Control of J chain biosynthesis in relation to heavy and light chain synthesis, polymerization and secretion. 80 6

The proteins programmed in the wheat-germ cell-free system by the mRNA coding for the MOPC-321 mouse myeloma L (light) chain were labelled with [35S]methionine, [4,5-3H]leucine or [3-3H]serine, and were subjected to amino acid-sequence analyses. Over 95% of the total cell-free product was sequenced as one homogeneous protein, which corresponds to the precursor of the L-chain protein. In the precursor, 20 amino acid residues precede the N-terminus of the mature protein. This extra piece contains one methionine residue at the N-terminus, one serine residue at position 18, and six leucine residues, which are clustered in two triplets at positions 6, 7, 8 and 11, 12, 13. The identification of methionine at the N-terminus of the precursor is in agreement with the evidence showing that unblocked methionine is the initiator residue for protein synthesis in eukaryotes. The absence of methionine at position 20, which precedes the N-terminal residue of the mature protein, suggests that myeloma cells synthesize the precursor. However, within the cell the precursor should be rapidly processed to the mature L chain, since precursor molecules have not yet been found in the intact animal. The abundance (30%) of leucine residues indicates that the extra-piece moiety is quite hydrophobic. The extra piece of the MOPC-321 L-chain precursor synthesized with the aid of the Krebs II ascites cell-free system is of identical size and it has the same leucine sequence [Schechter et al. (1975) Science 188, 160-162]. This indicates that cell-free systems derived from the plant and animal kingdom initiate mRNA translation from the same point. It is shown that the amino acid sequence of minute amounts of a highly labelled protein (0.1 pmol) can be faithfully determined in the presence of a large excess (over 2000 000-fold) of unrelated non-radioactive proteins.
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PMID:Identification of N-terminal methionine in the precursor of immunoglobulin light chain. Initiation of translation of messenger ribonucleic acid in plants and animals. 82 67

The proteins programmed in the wheat-germ cell-free system by the mRNA coding for the MOPC-63 mouse myeloma L (light) chain were labelled with six radioactive amino acids: [35S]methionine, [4,5-3H]leucine, [3,4-3H]proline, [3-3H]serine, [4,5-3H]isoleucine or [2,3-3H]alanine. Amino acid-sequence analyses showed that over 90% of the total cell-free product was one homogeneous protein, which corresponds to the MOPC-63 L-chain precursor. In this precursor an extra piece, 20 amino acid residues in length, precedes the N-terminus of the mature L chain. The extra piece contains one methionine residue at the N-terminus, six leucine residues, which are clustered in two triplets at positions 6, 7, 8 and 11, 12, 13, one proline residue at position 16, and one serine residue at position 18. The closely gathered leucine residues, as well as their abundance (30%), suggest that the extra-piece moiety is hydrophobic. In the precursors, the extra piece is coupled to the variable region of the L chain. Partial sequences of precursors of L chains of the same and different subgroups that were labelled with the above six radioactive amino acids indicate that the extra piece is part of the variable region. Thus the precursors of MOPC-63 and MOPC-321 L chains, which are of the same subgroup, have extra pieces of identical size (20 residues), and so far their partial sequences are also identical (see above). On the other hand, in the precursor of MOPC-41 L chain, which is of a different subgroup, the extra piece is 22 residues in length. Further, the sequence of the MOPC-41 extra piece differs in at least ten positions from sequences of the extra pieces of the precursors of MOPC-63 and MOPC-321 L chains.
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PMID:Amino acid-sequence variability at the N-terminal extra piece of mouse immunoglobulin light-chain precursors of the same and different subgroups. 82 40

Conditions influencing Ig secretion by plasma cells have been studied with suspensions of murine plasma cells and myeloma cells by determining the release of (3)H-Ig after a pulse of biosynthetic labeling with L- [4,5-(3)H]-leucine. Ig secretion is insensitive to a variety of hormones, mediators, cyclic nucleotide derivatives, extracellular calcium depletion, and agents acting on mierotubules or microfilaments; i.e., to a number of factors which are involved in the regulation of secretion by cells with a storage compartment. On the other hand, Ig secretion is markedly inhibited by conditions which (a) lower intracellular calcium levels (ionophore A 23187 in Ca(++)-free medium), (b) induce partial sodium/potassium equilibration (the ionophores monensin and nigericin and, in the case of myeloma cells, ouabain and incubation in K(+)-free medium) or (c) uncouple oxidative phosphorylation. The first two situations are accompanied by striking alterations of the ultrastructural appearance of the Golgi complex, different in each case. These ultrastructural observations, together with autoradiographic experiments after a short pulse with L-[4,5-(3)H]-leucine, have led to the following hypothesis: (a) under Ca(++) depletion (3)H-Ig passes to Golgi vesicles but these vesicles are incapable of fusion or migration and therefore accumulate in exaggerated numbers in the Golgi area; (b) under partial Na(+)/K(+) equilibration, (3)H-Ig passes to Golgi vesicles which have an exaggerated tendency to fuse with other Golgi elements, thereby generating large vacuoles which store increasing amounts of Ig; (c) under energy block, multiple membrane fission and fusion events are inhibited and there is therefore, little intracellular transport of (3)H-Ig or alteration of cell ultrastructure.
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PMID:Plasma cell immunoglobulin secretion: arrest is accompanied by alterations of the golgi complex. 92 6


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