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)

Binding constants of the dextran-reactive BALB/c mouse IgA myeloma proteins W3129 and QUPC 52 have been determined for each member of the isomaltose series of oligosaccharides and for methyl alphaDglucoside. Protein W3129 has maximum complementarity for isomaltopentaose (IM5) deltaf degrees = 7,180 cal/mol) with 55-60% of the total binding energy directed against methylalphaDglucoside. Protein QUPC 52 gives maximum binding with isomaltohexaose (IM6) (deltaF degrees = -5,340 cal/mol) and has about 70% of its total binding energy for isomaltotriose (IM3), but at most only 5% for isomaltose (IM2) or methyl alphaDglucoside. Protein W3129 precipitates with branched dextrans high in alpha (1 yields 6) linkages and reacts with but does not precipitate a synthetic alpha (1 yields 6)-linked linear dextran. Protein QUPC 52 precipitates both branched and linear dextrans. Thus, the immunodominant group for protein W3129 is mimicked by methyl alphaDglucoside and this protein reacts exclusively at the terminal nonreducing ends of alpha (1 yields 6)-linked dextran chains. Protein QUPC 52 has an immunodominant group which is expressed by IM3 but not smaller oligosaccharides and this protein can react at nonterminal locations along alpha (1 yields 6)-linked dextran chains. Precipitation of linear dextran seems to be a valid although not quantitative assay for antidextrans with nonterminal specificity. Quantitative precipitin reactions with branched and linear dextrans suggest that alpha (1 yields 6)-specific human antidextrans are mixtures of molecules having terminal and nonterminal specificities and that the fraction of each type can vary among individuals. Rabbit antisera against IM3 or IM6 coupled to bovine serum albumin also appear to contain antibodies with nonterminal specificity for dextran chains although a large fraction has terminal specificity. Low molecular weight clinical dextran N-150N (congruent to 60,000) reacted more like linear dextran than like its parent native-branched dextran B512. This is thought to result from an abundance of nonterminal determinants in clinical dextran N-150N but a very small number of functional terminal determinants per molecule. An appreciation of terminal and nonterminal specificities and of the different immunodominant structures in isomaltosyl chains has proven to be of a great value in understanding the immunochemical reactions of dextrans. Moreover, certain previous findings with fructosan-reactive mouse myeloma proteins and human antilevans (55, 84) also suggest terminal and nonterminal specificities for levan chains.
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PMID:Binding properties of immunoglobulin combining sites specific for terminal or nonterminal antigenic determinants in dextran. 4 89

Foreign-body and delayed hypersensitivity granulomas were induced in mice; and the dynamics of macrophages isolated from dispersed, 1--4-week-old lesions was delineated. The size and histologic complexity of the lesions increased as shown: adjuvant greater than schistosome egg greater than methylated bovine serum albumin greater than bead. Esterase staining, spreading on glass, and the percentage of Fc-receptor--bearing macrophages present in the various granulomas reflected the same gradient. The Fc receptors were examined by rosetting with rabbit-antibody--SRBC complex (EA). Whereas more than 90% of the population of macrophages of the dermal adjuvant granuloma contained undiminished numbers of receptor-bearing macrophages throughout the 4 weeks, the percentage of macrophages that displayed receptors in pulmonary foreign-body (40%) and delayed hypersensitivity granulomas (70%) peaked at 1 week and subsequently declined. The EA rosetting of the foreign-body and delayed hypersensitivity granuloma macrophages was strongly inhibited by monomeric IgG2a-specific and weakly by aggregated IgG2b-specific mouse myeloma proteins. Also, macrophages of the delayed hypersensitivity granulomas rosetted in higher percentages with SRBCs coupled with monomeric IgC2a than with those coupled with aggregated IgG2b myeloma proteins. Macrophages of the foreign-body lesion did not react with aggregated IgG2b--SRBC. Rosetting with monomeric IgG2a--SRBC or aggregated IgG2b--SRBC could not be cross-inhibited by the myeloma proteins. Both the monomeric IgG2a--SRBC and aggregated IgG2b--SRBC complexes were readily phagocytized. Trypsin treatment of the macrophages inhibited rosetting with EA or myeloma-protein--coupled SRBCs. The display of Fc receptors on the granuloma macrophages seems to be related to the etiology of the lesion and the intensity and duration of the inflammatory reaction.
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PMID:Fc-receptor-bearing macrophages isolated from hypersensitivity and foreign-body granulomas. Delineation of macrophage dynamics, fc receptor density/avidity and specificity. 38 65

Human monocytes in culture release small amounts of prostaglandin E (PGE) into the medium. Addition of Fc fragments of IgG to human monocyte monolayer cultures results in a marked increase in PGE release; Fab fragments, monomeric IgG, and human serum albumin have no effect. An IgG1 myeloma has no effect on PGE levels but addition of the heat aggreagted protein results in a marked increase of PGE secretion. Exposure of the cells to Con A, which binds to a specific monocyte plasma membrane receptor, also results in a large increase in PGE release. The magnitude of the increase in PGE secretion produced by exposure of the monocytes to these ligands greatly exceeds the stimulation observed after the addition of antigen-activated mononuclear cell supernatants, zymosan, Sephadex beads, or endotoxin, to monocyte cultures. Prostaglandin E2 (PGE2) accounts for approximately 70% of the total prostaglandins released by stimulated cells. After addition of Indomethacin to monocyte cultures, the stimulatory effects of the ligands on PGE release are inhibited. Addition of Con A to monocyte cultures results in an increased incorporation of [3H]-arachidonic acid into PGE2. These results suggest that this ligand stimulates synthesis as well as release of this prostaglandin.
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PMID:Increased prostaglandin production by human monocytes after membrane receptor activation. 44 42

Two hundred forty-one patients with a monoclonal protein in the serum but initially no evidence of multiple myeloma, macroglobulinemia, amyloidosis or lymphoma were followed up for more than five years. At the conclusion of the studies the patients were classified as follows: Group 1, patients without significant increase in monoclonal protein, 57 per cent; group 2, patients with more than 50 per cent increase in monoclonal serum protein or development of monoclonal urine protein, 9 per cent; group 3, patients who died without five-year serum studies, 23 per cent; and group 4, patients in whom myeloma, macroglobulinemia or amyloidosis developed, 11 per cent. Initially, the hemoglobin level, size of serum monoclonal protein peak, number of plasma cells in the bone marrow and levels of normal immunoglobulins were not significantly different among the four groups. The median interval from recognition of the monoclonal protein to diagnosis of multiple myeloma was 64 months, of macroglobulinemia 103 months and of amyloidosis 92 months. A significant increase of the monoclonal protein or development of myeloma, macroglobulinemia or amyloidosis occurred in 18 per cent of the patients with monoclonal immunoglobulin G(IgG), in 28 per cent with immunoglobulin A (IgA) and in 25 per cent with immunoglobulin M (IgM). Retrospective analysis of age, sex, presence of organomegaly, hemoglobin level, size and type of serum monoclonal protein peak, presence of small amounts monoclonal light chain in the urine, serum albumin level, levels of uninvolved immunoglobulins, IgG subclass and level of plasma cells in the bone marrow did not show how to distinguish initially between stable benign disease and progressive disease. Therefore, periodic reexamination of patients with monoclonal gammopathy is essential.
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PMID:Monoclonal gammopathy of undetermined significance. Natural history in 241 cases. 64 46

Erythropoietin activity in serum was measured using 59Fe incorporation into erythrocytes in protein-starved, hypoxic mice. The activity in serum from 20 patients with untreated myelomatosis was not significantly different from that in 31 saline controls. Only three patients had detectable erythropoietin levels in serum: 0.24 IU/ml, 0.27 IU/ml and 0.50 IU/ml (standard B), respectively. The venous haematocrit was correlated positively with the glomerular filtration rate as measured by 51Cr EDTA-clearance. No correlation could be established between venous haematocrit and serum albumin or serum transferrin. The results are in agreement with the assumption of a defective erythropoietin activity due to renal failure in myelomatosis.
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PMID:Serum erythropoietin in myelomatosis. 88 35

Syngeneic mice of the C3H/He strain have been inoculated with cells of the plasmocellular tumours X5563 and X5647, producing myeloma proteins of the IgG and IgA class respectively, and were immunized with (1) sheep red blood cells, (2) bovine serum albumin and (3) horseradish peroxydase. The immune responses of the various groups of mice were followed. The antibody activities towards all three antigens were decreased in mice carrying the IgG producing tumour X5563. This effect was correlated with an enhanced catabolism of IgG as well as with a decrease in number of IgG antibody producing cells. A reduced immune response was also observed in mice to which the IgA producing tumour X5647 had been transferred, but the effect was significantly less pronounced. There was no effect at all observed on the IgM response. The avidity which was measured for the various IgG antibodies was not modified by the presence of IgG nor IgA secreting myeloma tumours.
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PMID:[The influence of plasmocellular tumours on the humoral immune response in mice (author's transl)]. 95 95

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

During a 40 month interval, 35 patients were seen with a plasma cell dyscrasia in which the only detectable monoclonal immunoglobulin abnormality consisted of excess production of either type kappa or type lambda light chains (Bence Jones protein). This group constituted 17.3 per cent of the total number of patients with plasma cell dyscrasias and 25.7 per cent of the patients with myeloma identified during the same period. Variable initial clinical presentation, the absence of a typical monoclonal serum spike and the unreliability of commonly used urine protein tests made recognition of the disorder difficult in many patients. Sulfosalicylic acid and p-toluene sulfonic acid proved valuable in screening for ueine protein. Definition of "proteinuria" by quantitative, electrophoretic and immunochemical studies was essential for diagnosis. Bence Jones proteinemia was present in 80 per cent of the patients; panhypogammaglobulinemia and lytic bone lesions were demonstrable in more than 60 per cent. Although no specific morphologic abnormality of marrow plasma cells was evident by light microscopy, the absence of rouleau on peripheral blood smear was a helpful diagnostic clue. Although patients with lambda light chains presented with more Bence Jones proteinuria, this did not correlate with the severity of initial renal functional impairment or with survival when compared to patients with kappa light chains. No other clinical or laboratory observation differentiated the groups with kappa light chains from those with lambda light chains. Amyloid was identified in seven patients. Their course was dominated by the features of primary systemic amyloidosis instead of the usual findings of classic myeloma. Patients with amyloidosis had lower initial serum albumin levels, fewer lytic bone lesions and reduced survival compared to patients without amyloidosis.
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PMID:The clinical spectrum of light chain myeloma. A study of 35 patients with special reference to the occurrence of amyloidosis. 113 Apr 19

A monoclonal antibody against cis-3-hexen-1-ol was prepared and used to separate and/or concentrate delta 17-6-keto-prostaglandin F1 alpha (PGF1 alpha) in the human sera. cis-3-Hexen-1-ol was conjugated with the human serum albumin (HSA) according to the N-succinimidylester method and hyperimmunized to BALB/c mouse. The monoclonal antibodies were obtained from hybridoma clones established by a fusion between SP2/0-Ag14-k13 mouse myeloma cells and splenocytes of a mouse. A monoclonal antibody, named 4G9-12B, recognized the epitope characteristic for omega 3-olefin structure. The 4G9-12B antibody became more specific for delta 17-6-keto-PGF1 alpha than 6-keto-PGF1 alpha by applying inhibition ELISA using amino-residue coating plates. Using the prepared immunoaffinity columns of this antibody, delta 17-6-keto-PGF1 alpha was clearly detected in 6 pg/ml of the human blood sera by GC/MS analysis. These results suggest that the monoclonal antibody to the partial structure of trienoic prostanoid, omega 3-olefin unit, and that its immunoaffinity columns are useful in separating and concentrating delta 17-6-keto-PGF1 alpha in the human blood or urine.
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PMID:Separation and concentration of delta 17-6-keto-PGF1 alpha using monoclonal antibody to omega 3-olefin structure of trienoic prostanoids. 127 46

An improved knowledge of the initial prognostic factors of multiple myeloma and regular monitoring of the disease should result in the choice of the most effective treatment. The conventional prognostic factors have been divided into three stages by Durie and Salmon. These stages are based on the proportion and type of the monoclonal component, on haemoglobin, calcium and creatinine blood levels and on the extent of bone lesions. However, this widely used classification has certain disadvantages: the size of the tumoral mass is evaluated mainly from the proportion of monoclonal gammopathy, the bone lesions are difficult to determine and the kinetics of cell proliferation are not taken into account. Parameters with high prognostic value have recently been demonstrated; they include beta 2-microglobulin, LDH, interleukin-6, C-reactive protein, serum albumin and kinetic of cell proliferation. When associated, these data allow to establish prognostic staying that are at least as relevant as those of the Durie-Salmon's classification. Monitoring of patients with multiple myeloma by means of a time-related curve of either the tumoral mass or the amount of monoclonal gammopathy leads to the best possible treatment.
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PMID:[Prognostic factors and monitoring of myeloma]. 128 67


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