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)

Human chromosome 3 has been identified as responsible for expression of the transferrin receptor in mouse-human lymphocyte hybrids. The receptor was detected by immunoprecipitation with anti-human receptor antibody of 125I-labeled cells. This method also detected a similar 94,000-dalton protein in mouse cells. A radioimmunoassay developed for the human transferrin receptor measured 10% crossreactivity with the mouse protein. The two proteins were distinguished by NaDodSO4/polyacrylamide gel patterns of partial proteolytic digests of the immunoprecipitated proteins. Mouse-human hybrids were generated by fusing a mouse thymoma (BW5147) cell line to either concanavalin A- or pokeweed mitogen-activated human peripheral blood lymphocytes or a mouse myeloma (NS-1) to uncultured human peripheral blood lymphocytes. Each hybrid was karyotyped with respect to both mouse and human chromosomes. In every case, expression of the human transferrin receptor correlated only with human chromosome 3.
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PMID:Human transferrin receptor: expression of the receptor is assigned to chromosome 3. 628 43

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

The plasma cell alloantigen PC-1 was isolated from C1.18 myeloma cells by immunoprecipitation and was analyzed by polyacrylamide gel electrophoresis. It was found to consist of two similar or identical disulfide-bonded polypeptide chains, each of Mr 115,000. The mobility of PC-1 in nonequilibrium pH gradient electrophoresis was similar to that of bovine serum albumin (pI 4.9). The PC-1 antigen is therefore similar to the transferrin receptor in Mr, charge, subunit composition, disulfide bonding, and developmental regulation. Similarities can also be detected by peptide mapping with subtilisin, but not with staphylococcal V8 protease. It is suggested that the PC-1 protein and the transferrin receptor may have had a common evolutionary origin, and may have similar functions.
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PMID:Structure of the murine plasma cell alloantigen PC-1: comparison with the receptor for transferrin. 629 94

Detergent-solubilized plasma membranes of Con A-activated mouse spleen cells were absorbed with Sepharose-coupled rat antibodies against resting mouse lymphocytes. The unbound fraction was used to immunize a rat, and the immune spleen cells were fused with the rat myeloma Y3 . All seven rat monoclonal antibodies produced in this way strongly reacted with mitogen-activated spleen cells but only weakly or insignificantly with unstimulated spleen cells. One of the antibodies, YE3 /19.1, was studied in detail. The antibody strongly reacted with Con A- or LPS-stimulated spleen cells, but not significantly with normal adult thymocytes, spleen cells, or bone marrow cells. Unlike the transferrin receptor, which is expressed on virtually all dividing cells, the antigen defined by YE3 /19.1 was not detected on erythroblast-enriched populations or some non-T, non-B cell lines. Therefore, the antigen, termed MALA-1, seems to be specific for activated murine lymphocytes of the T and B cell lineages. Over 25% of normal adult lymph node cells were also found to express the antigen, although the antigen densities on lymph node cells were lower than those on mitogen-stimulated spleen cells. Kinetic studies of the expression of MALA-1 and the transferrin receptor on Con A-activated spleen T cells showed that both antigens are detectable within 24 hr of Con A stimulation. Although the density of the transferrin receptor on Con A blasts declined as the cell proliferation ceased, MALA-1 expression persisted. Immunoprecipitation of MALA-1 from surface-iodinated Con A blasts revealed its m.w. to be approximately 14,000 to 18,000.
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PMID:MALA-1: a surface antigen expressed on activated murine T and B lymphocytes. 660 86

The most common cause of limited response to recombinant human erythropoietin (r-HuEPO) is unrecognized, mild-to-moderate iron deficiency, either at the start of treatment or secondary to enhanced iron utilization by newly formed erythrocytes. Iron stores in patients with chronic renal failure (CRF) are often depleted through gastrointestinal bleeding, blood loss during haemodialysis, and blood sampling. Mobilization of iron stores may be inadequate, especially during rapid haemoglobin regeneration. Aluminium overload may also interfere with gastrointestinal and cellular iron uptake. Overt or unrecognized infection or inflammation is another common cause of hyporesponsiveness, and is a consequence of increased blood concentrations of cytokines such as tumour necrosis factor (TNF), interleukin-1 (IL-1), and interferon-gamma (IFN-gamma), which suppress erythrocyte stem-cell proliferation. Less common causes include severe secondary hyperparathyroidism and myeloma (during chemotherapy). Response to r-HuEPO can be best predicted by baseline fibrinogen (a marker of subclinical inflammation); baseline transferrin receptor (sTfR) concentrations (a marker of functional iron deficiency); and sTfR increment after 2 weeks (a marker of early change in erythropoietic activity).
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PMID:R-HuEPO hyporesponsiveness--who and why? 764 9

A 75-year-old female was diagnosed as having multiple myeloma (IgG.lambda type. Stage IIA) with plasmacytoma of the head and back in October, 1989. She obtained partial remission by MCNU and MP therapy, but relapsed with massive ascites in January, 1991. VAD therapy was not effective and she died of multiple organ failure on February 23. Her ascites contained a large number of myeloma cells, and the phenotypic analysis and the response to interleukin-6 (IL-6) of these myeloma cells were examined. The myeloma cells were positive for CD33, CD45, CD45RA, CD63, CD71, plasma cell associated antigens such as CD38, PCA-1, BL3, and various kinds of adhesion molecules: CD11a/CD18 (LFA-1), CD29 (VLA-beta 1), CD44 (H-CAM), CD49d (VLA-4), CD54 (ICAM-1), CD56 (N-CAM), CD58 (LFA-3). IL-6 level in the ascites was increased at 91.0pg/ml. The myeloma cells showed an IL-6 dependent growth, which was inhibited by anti-IL-6 antibody (Ab) and anti-IL-6 receptor Ab in vitro. Myeloma cells appearing in ascites have rarely been reported. Our case suggested that IL-6 was a potent growth factor of myeloma cells through an autocrine mechanism in the ascites, and resulted in an aggressive myeloma.
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PMID:[Multiple myeloma with massive ascites fluid--immunophenotypic analysis of myeloma cell and its IL-6-dependent growth]. 786 16

We measured the soluble (s) receptors CD23, CD8, CD4, interleukin-2 receptor (IL-2R, CD25), and transferrin receptor (TfR, CD71), in normal serum and in patients with chronic lymphocytic leukemia (CLL) and evaluated them in relation to clinical and biological parameters of the disease, as well as serum immunoglobulin E (IgE). Compared to 31 normal individuals, 42 CLL patients had increased levels of sCD23 (98.4 +/- 127.7 versus 0.9 +/- 0.3 U/ml, p < 0.001), sIL-2R (6080 +/- 7030 versus 1420 +/- 640 pg/ml, p < 0.001), sTfR (12,100 +/- 11,250 versus 5000 +/- 1050 ng/ml, p < 0.001), and sCD8 (510 +/- 191 versus 234 +/- 89 U/ml, p < 0.001), but normal sCD4 levels. Mean sCD23 levels remained normal in patients with non-Hodgkin's lymphoma (other than small lymphocytic), Hodgkin's disease, hairy cell leukemia, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), multiple myeloma, or solid tumors. Advancing Rai clinical stage was associated with a progressive elevation of sCD23 (p < 0.001), while sCD8 (p < 0.05), sIL-2R (p < 0.001), and sTfR (p < 0.005) were highest in stage 2 patients. Discriminant analysis confirmed the value of soluble receptor determinations in the clinical evaluation of CLL patients. sCD23 correlated with sIL-2R (p < 0.001) and sTfR (p < 0.05) but not with sCD4 or sCD8, and displayed an inverse relationship with serum IgE (NS) and total gamma-globulin (p < 0.05). sIL-2R correlated with sCD23 (p < 0.001), sTfR (p < 0.001), sCD4 (p < 0.01), and sCD8 (p < 0.01). The lymphocyte count correlated with serum lactate dehydrogenase (LDH) (p < 0.05), sCD23 (p < 0.001) and sIL-2R (p < 0.01) but not sTfR, sCD8, or sCD4. Chemotherapy produced consistent reductions of sCD23 levels in two responding patients. We conclude that: (i) sCD23 is considerably elevated in CLL, correlates with the tumor mass and clinical stage, and could be helpful in monitoring these patients; and (ii) sIL-2R, sCD8, and sTfR levels are less specifically increased and could be influenced by other factors such as immune activation and erythropoiesis.
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PMID:Soluble CD23 and other receptors (CD4, CD8, CD25, CD71) in serum of patients with chronic lymphocytic leukemia. 825 2

A review is given of the prognostic significance of immunophenotyping of blood lymphoplasmocytic cells. From a group of 250 patients followed from 1981 through 1991 a subgroup of 70 patients (followed 1986 through 1991) were phenotyped at 6-month intervals by immunofluorescence tests with monoclonal antibodies for cytoplasmic immunoglobulin, kappa-lambda index, CD71, CD10, CD20, CD38, and HLA-DR receptors. In course of a longitudinal study it was found that prognostic significance for shortened survival can be derived from the presence of circulating CD10, CD71, and CD20 positive undifferentiated cells in peripheral blood. There was a correlation between increase of CALLA positive and CD71 positive cells. Further, an increase of undifferentiated clone occurred during transition of the disease to an aggressive phase. The median survival of the total group of 250 patients treated by the VMCP/MOCCA protocol, according to statistical analysis, was 90 months, the median survival of the aggressive stage with plasmoblastic and lymphoplasmocytic cell type, respectively, was only 12 months. The significance of phenotypization in the prognostic evaluation of variant heterogenous myeloma types is stressed.
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PMID:Prognostic value of plasma-cell immunophenotype in patients with multiple myeloma. 828 66

In this review, the pathophysiology and treatment of the anemia of multiple myeloma will be examined. While the anemia of cancer has multiple causes, an important component is labeled the "anemia of chronic disease" which is characterized by the combination of a shortened erythrocyte survival with failure of the bone marrow to increase red cell production in compensation. Depressed erythropoiesis is itself related to a combination of factors, including impaired availability of storage iron, inadequate erythropoietin response to anemia, and overproduction of cytokines which are capable of inhibiting erythropoiesis. These cytokines are involved in the retention of iron in the reticuloendothelial system, gastrointestinal tract and hepatocytes, may interfere with erythropoietin production by the kidney, and may exert direct inhibitory effects on erythroid precursors. While overproduction of several such cytokines, including IL-6, IL-1 and TNF-alpha, has been definitely demonstrated in multiple myeloma patients, it is still unclear whether they are directly involved in the pathogenesis of the anemia which develops. Although several mechanisms, such as hemodilution, bleeding, and decreased red cell survival operate, the anemia is mostly caused by defective erythropoietic activity. This in turn is partly explained by inadequate erythropoietin (Epo) production even in some patients without renal impairment. Based on measurements of serum erythropoietin and transferrin receptor, the distinction between marrow unresponsiveness to normal Epo stimulation and deficient Epo production is important for the treatment of the anemia of multiple myeloma with recombinant human Epo. Higher doses would probably be necessary if adequate Epo production is present, whereas only replacement therapy with lower doses may be sufficient when Epo production has been shown to be inappropriate.
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PMID:Erythropoiesis and erythropoietin in multiple myeloma. 852 47

The existence of an ecto-sialyltransferase (ecto-ST) on B lymphocytes with increasing activity at late maturation stages is shown using a novel flow cytometric enzyme assay. This ecto-ST is effective in reconstituting different surface glycoconjugates on desialylated B cells in the presence of exogenous CMP-NeuAc. We found that this ecto-ST is distinct in its activity from soluble ST released into the culture supernatant. Surface sialylation was independent of the amount of ST secreted into the culture supernatant and followed different kinetics than sialylation of exogenous substrate by soluble ST. Four human B-cell lines representing different maturation stages were analyzed for secreted and ecto-ST activity. The myeloma cell line U266 and the lymphoblastoid cell line JOK-1 showed higher activity of both ST forms than the acute lymphoblastic leukemia B-cell line Nalm-6. ST activity in culture supernatants of U266, JOK-1, and Nalm-6 cells consisted predominantly of the alpha 2,6 ST type with specificity for N-linked oligosaccharides. As an exception, the myeloma cell line IM-9, deficient of alpha 2,6 ST activity, secreted only small amounts of ST and showed low activity of ecto-ST. Sialylation of surface-expressed glycoconjugates by ecto-ST was measured by incubating B-cell lines in the presence of fluorescent CMP-sialic acid. Surface structures labeled with fluorescent sialic acid under this condition were visualized by confocal laser scanning microscopy and fluorescent label was quantitatively assessed by flow cytometric analysis on live cells. Incubation of cells in acidified culture medium, to release possibly receptor-bound ST, did not alter the intensity of cell surface sialylation. Inhibition of internalization and membrane traffic by various approaches (reduced incubation temperature and chloroquine or brefeldin A treatment) did not block surface sialylation. Together, these observations point to cell surface sialylation in B lymphocytes mediated by a cell surface-expressed ecto-ST distinct from the secreted ST form. On desialylated JOK-1 cells, ecto-ST in the presence of exogenous CMP-NeuAc was able to resialylate the B-cell surface sialoglycans CDw75 and HB-6 and major surface glycoproteins of B cells, such as HLA class I and II antigens, transferrin receptor, and surface IgM. In contrast, cell surface glycans of coincubated desialylated erythrocytes were not sialylated by the B-cell ecto-ST. Ecto-alpha 2,6 ST of B cells may be involved in the sialylation of distinct differentiation glycan antigens.
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PMID:Ecto-sialyltransferase of human B lymphocytes reconstitutes differentiation markers in the presence of exogenous CMP-N-acetyl neuraminic acid. 865 24


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