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)

Haptoglobin and transferrin types were determined for 27 multiple myeloma patients and a series of case controls. No association was found between haptoglobin and the disease, which confirms the findings of an earlier investigation. However, we found a significantly increased relative risk of 2.6 for TFC1C1 individuals. It is suggested that the role of transferrin in erythropoiesis and cell proliferation of both malignant and normal cells, may, at least in part, explain the association. Of additional relevance may be the suggestion that TFC1C1 individuals have higher blood iron levels than other subtypes.
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PMID:Haptoglobin groups and transferrin subtypes in multiple myeloma. 337 97

Ribonucleotide reductase from Escherichia coli consists of two nonidentical subunits, named protein B1 (170 000) and protein B2 (87 000). We purified and characterized five monoclonal antibodies against B1 and three against B2 from hybridomas obtained by fusion of spleen cells from immunized mice and the myeloma cell line P3-X63Ag8. All are of the IgG1 class with a high affinity for the antigen with dissociation constants in the nanomolar range. Four of the anti-B1 monoclonals and all three anti-B2 monoclonals neutralize reductase activity while one anti-B1 monoclonal binds tightly to B1 without affecting its activity. Fab fragments prepared from three anti-B1 monoclonals had similar dissociation constants. The anti-B1 monoclonals interacted with separate epitopes while two of the anti-B2 monoclonals appeared to react with the same epitope. In the case of B1, various allosteric states of the protein induced by binding of effectors had no apparent effect on the interaction with monoclonals, nor did their binding prevent subsequent binding of effectors. With B2, binding of monoclonals did not affect the typical electron paramagnetic resonance spectrum of the protein and thus did not involve either the tyrosyl free radical or the iron center of B2. All neutralizing antibodies interfered with the interaction between the two subunits, explaining their effect on enzyme activity, since active ribonucleotide reductase consists of a B1-B2 complex.
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PMID:Production and characterization of monoclonal antibodies against the two subunits proteins B1 and B2 of Escherichia coli ribonucleotide reductase. 351 10

The serum ferritin concentration is increased in both acute myeloblastic leukaemia and Hodgkin's disease. In acute leukaemia the mean concentration is about ten times the normal level and is associated with a high concentration of transferrin-bound iron. In Hodgkin's disease abnormal ferritinaemia is associated with a low concentration of transferrin-bound iron and appears to result from a block of reticuloendothelial iron release. Increased concentrations of circulating ferritin have also been observed in a few cases of chronic leukaemia and myelomatosis.
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PMID:Ferritinaemia in leukaemia and Hodgkin's disease. 451 89

Monolayer cultures of ARH-77 cells, a human myeloma cell line propagated in vitro, display a variety of morphologic entities ranging from small lymphocytes to classic plasma cells. The cells show intense pyronin and periodic acid-Schiff affinity but are negative for colloidal iron, sudan black, and naphtol AS-D chloroacetate esterase. The cells exhibit phenotypic markers pertaining to each stage of the B-cell lineage. They fail to display sheep erythrocyte and bovine erythrocyte-IgG antibody complex rosettes, common acute lymphocytic leukemia (ALL) antigens and T-cell antigens, but most cells display surface complement receptors, Ia-like antigens, and surface and intracytoplasmic Ig. Monoclonal antibodies were negative for T-antigens, myelomonocytic cell antigens, leukemia-associated antigens, and BA-1 and OKT-10 antigens. However, 100% of the cells were positive with OKT-9 and B3/25 antibodies that are specific for transferrin receptors. About 50% to 80% of the cells were positive for surface membrane immunoglobulin (kappa IgG) and about 10% to 50% for cytoplasmic immunoglobulin (kappa IgG). Virtually all cells were positive when tested for nuclear Epstein-Barr virus antigens.
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PMID:ARH-77, an established human IgG-producing myeloma cell line. I. Morphology, B-cell phenotypic marker profile, and expression of Epstein-Barr virus. 609 3

The receptor for transferrin is one of the major surface proteins of proliferating lymphocytes and other cells. It binds ferrotransferrin from serum and endocytoses it into an acidic nonlysosomal intracellular compartment where iron is released, but in which apotransferrin remains tightly bound to its receptor. Recycling of the apotransferrin-receptor complex to the cell surface is associated with a return to neutral pH and concomitant loss of affinity of apotransferrin for its receptor. Apotransferrin is then free to leave the cell and initiate a new cycle. We have exploited this cycle in a novel method for the purification of the receptor for transferrin. Murine myeloma cells were lysed in nonionic detergent, and the lysate passed over a column of ferrotransferrin-agarose at pH 7.4. After washing with sodium acetate at pH 5.0, iron was removed with sodium citrate pH 5.0 and desferrioxamine. Upon returning the pH to neutrality, the receptor was eluted and found to be homogeneous by SDS-polyacrylamide gel electrophoresis under both reducing and nonreducing conditions. The degree of purification was estimated to be at least 3,000-fold, and the calculated yield was 10 to 20%. The purified receptor was capable of binding to transferrin. The receptor was digested with trypsin, and the resulting peptides were separated by reversed-phase high performance liquid chromatography in NH4HCO3. Selected peptides were rechromatographed in 0.1% trifluoroacetic acid, and their amino acid sequences were determined.
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PMID:The receptor for transferrin on murine myeloma cells: one-step purification based on its physiology, and partial amino acid sequence. 609 68

A rat monoclonal antibody against the murine transferrin receptor has been identified. The receptor is a 95,000 molecular weight species that exists in the cell membrane as a disulphide-bonded dimer. Whereas 29 of 29 murine hematopoietic tumor cell lines express detectable numbers of transferrin receptors, less than 1% of adult thymocytes or spleen cells and only 5% of bone marrow cells are positive. However, fetal liver and neonatal spleen contain substantial numbers of transferrin receptor-positive cells. Induction of Friend cells in vitro with dimethyl-sulphoxide leads to an overall increase in the expression of transferrin receptors on the cell surface. The anti-transferrin receptor antibody we have obtained partially blocks iron uptake from 59Fe-transferrin by a variety of murine cell lines and inhibits the growth of a murine myeloma cell line in vitro.
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PMID:Murine cell surface transferrin receptor: studies with an anti-receptor monoclonal antibody. 629 May 5

Multiple myeloma is a malignancy characterized by uncontrolled monoclonal B cell differentiation and immunoglobulin production. In most instances, there is concomitant reduction in polyclonal differentiation and immunoglobulin synthesis both in vivo and in vitro. In in vitro pokeweed mitogen-induced B cell differentiation assays, proliferation and polyclonal immunoglobulin secretion optimally requires T cell help and can be inhibited both by monocytes and suppressor T cells. Helper function and monocyte-mediated suppression are relatively radio-resistant whereas T suppressor function is sensitive to 2,000 rad x-irradiation. We have examined myeloma T cell subset function in this assay using recombinations of isolated patient and normal B cells, T cells, and T cell subsets. Monocytes were removed by a carbonyl iron ingestion technique, normal and myeloma T cells were fractionated on the basis of Fc receptors for immunoglobulin (Ig) G (Tgamma) or IgM (Tmu or T non-gamma), and proliferation and IgG secretion after co-culture determined by [(3)H]thymidine incorporation and radio-immunoassay, respectively. Myeloma B cells demonstrate quantitatively and qualitatively normal blastogenic responses and are appropriately regulated by either autologous or allogeneic T helper and suppressor subsets. Despite normal proliferation, however, myeloma B cells remain deficient in subsequent differentiation and immunoglobulin secretion even when co-cultured in the absence of monocytes or suppressor T cells and the presence of normal helper cells. Myeloma T cell populations, in contrast, are entirely normal in helper capacity over a range of T:B ratios but are markedly deficient in radiosensitive and concanavalin A-induced suppressor activity. T suppressor cell dysfunction in multiple myeloma is apparently due to a deficit in the T non-gamma suppressor subset, whereas Tgamma cells, although proportionately reduced, are functionally normal. This unique T suppressor deficit reflects the heterogeneity of suppressor mechanisms in this disease and may represent a compensatory response to the monoclonal proliferation or the involvement of regulatory T cells in the pathogenesis of the malignancy.
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PMID:Immunoregulatory T cell function in multiple myeloma. 645 35

Twenty-four untreated patients with myelomatosis were studied in order to characterize their anaemia, using standard haematological and ferrokinetic techniques, together with measurements of circulating erythropoietin, erythropoietin sensitivity of marrow cultures and in vitro measurements of haem synthesis. There is a reduction in total erythroid output by the marrow, together with a minor degree of plasma expansion. In patients with normal renal function there is an appropriate increase in erythropoietin in response to anaemia, but in a few cases there may be reduced response of CFU-E to the hormone in vitro. No abnormality of iron status or haem synthesis was found. One case of folate deficiency was discovered.
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PMID:Anaemia in patients with myelomatosis. 709 23

A 56-year-old man with diffuse cutaneous xanthomatosis had neither mucosal lesions nor diabetes insipidus. Cutaneous lesions were characterised by dermal histiocytic infiltration, without X bodies, associated with Touton's cells and abundant iron deposits. Plasma lipid levels were normal. A lambda G monoclonal dysglobulinemia was present without Bence-Jones proteinuria or myeloma, except for a moderate increase in medullary plasmocytic cell elements. The diagnosis of disseminated xanthomatosis was established, the differential diagnosis from other histiocytic proliferations, particularly diffuse plane xanthoma, being sometimes difficult. The relation between normolipaemic xanthomatosis and dysglobulinemia certainly exists, but no satisfactory pathogenic explanation was possible in this case, in the absence of cryoglobulin, paraprotein antilipoprotein activity, and cutaneous deposits of lipoprotein-paraprotein complexes.
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PMID:[Diffuse normolipemic xanthomatosis and IgG monoclonal dysglobulinemia]. 718 Dec 45

Bone marrows of 38 patients have been investigated for iron-containing plasma cells. Two patterns emerged. One consisting of iron-laden plasma cells involving myeloma, iron overload and megaloblastic anaemia patients. The second showing no iron in plasma cells of patients with anaemia of chronic disease (ACD). Electron microscopy was done on 3 patients who had excess iron in their bone marrow particles and plasma cells. Perls' stain and scanning transmission electron microscopy were used to confirm the presence of iron in bone marrow plasma cells. The results show that the uptake of iron by plasma cells is dependent on marrow iron stores and the availability of the iron for uptake.
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PMID:Iron uptake by plasma cells in haematological disorders. 753 93


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