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)

Changes in rat mast cell cyclic adenosine 3',5' monophosphate (cAMP) concentrations during stimulation of histamine release by concanavalin A (con A) and anti-IgE were studied. Con A caused an increase in cAMP with a mean peak level at 20 sec of 232% of control (range 164% to 365%). Con A-stimulated cells demonstrated falls toward control levels after 20 sec, but generally remained above control for at least 5 min. By 10 min cAMP had returned to control values. The con A effect on cAMP occurred in the absence of phosphatidyl serine but was markedly inhibited by 5 mM alpha-methyl-D-mannose. Anti-IgE induced a less marked increase in cAMP (157% of control, range 110% to 540% of control) which reached a peak at 20 sec. Two monospecific goat anti-rat myeloma IgE antisera induced similar changes in cAMP whereas normal goat IgG had no effect. These peak values were followed by a rapid decrease in cAMP. Within 2 min the cAMP content of anti-IgE stimulated cells had fallen to levels well below control and remained below control levels from 45 sec to over 15 min. Histamine release in both systems began after the peak cAMP levels, during the period of rapid destruction of cAMP.
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PMID:Modulation of cyclic AMP in purified rat mast cells. III. Studies on the effects of concanavalin A and anti-IgE on cyclic AMP concentrations during histamine release. 6 Apr 47

Culture filtrate extracts from a number of dermatophyte and Aspergillus species precipitate with human C-reactive protein (CRP) and the lectin Con A. Using immobilized Con A, a peptidopolysaccharide (PPS) has been isolated from Epidermophyton floccosum culture filtrate by affinity chromatography and shown to precipitate with Con A, human CRP sera and a mouse myeloma serum with specificity for phosphorylcholine (PC). The PPS contains carbohydrate (60%), protein (35%), choline and phosphate. The carbohydrate portion consists almost entirely of D-mannose with only 2% hexosamine. Amino acid analysis revealed that serine, threonine, proline and glycine accounted for over 50% of the total amino acids present. Precipitation of E. floccosum PPS and pneumococcal C substance with human CRP sera and mouse anti-PC serum were compared in quantitative precipitin studies. Inhibition studies demonstrated that PC is a potent inhibitor of the serum CRP-PPS and myeloma protein-PPS precipitation reactions. The involvement of 'C substances' in a variety of biological processes is discussed.
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PMID:Isolation of a peptido-polysaccharide from the dermatophyte Epidermophyton floccosum and a study of its reaction with human C-reactive protein and a mouse anti-phosphorylcholine myeloma serum. 88 87

We describe a method, called affinity partitioning, for the purification of proteins containing specific ligand binding receptor sites. This method adds specificity to the procedures for protein purification with aqueous polymer two-phase systems by introduction of a polymer derivative, coupled to an appropriate ligand. The addition of a polymer-ligand that partitions predominantly into one phase shifts the protein that binds this substance to the same phase. By performing countercurrent distribution in the presence of a polymer-ligand, the protein that binds the polymer-ligand can be separated from a heterogenous mixture. One example of affinity paritioning used dextran as the polymer-ligand. Dextran was chosen since it is a constituent of the most commonly used system for partitioning proteins. In a dextran-poly(ethylene oxide) system, concanavalin A bound dextran and partitioned predominantly into the dextran-rich phase. The addition of the specific competitor, D-mannose, displaced the partition coefficient toward unity, while the application of L-fucose, a noncompetitor, had little effect. Application of affinity partitioning to the purification of another protein required the synthesis of a specific polymer-ligand. To study this we synthesized dinitrophenyl-poly-(ethylene oxide), which binds specifically to S-23 myeloma protein. Addition of dinitrophenyl-poly(ethylene oxide) to the dextran-poly(ethylene oxide) phase system shifted the S-23 myeloma protein into the poly(ethylene oxide)-rich phase. epsilon-N-dinitrophenyl-L-lysine, by competing with binding of dinitrophenyl-poly(ethylene oxide), antagonized the latter's effect on the partition coefficient of S-23 myeloma protein. By adding various amounts of dinitrophenyl-poly-(ethylene oxide), we correlated the partition coefficient with concentration of polymer-ligand. A model of the action of polymer-ligand derivatives on the partition coefficient, derived from thermodynamic considerations, was found to be consistent with the experimental data relating the concentration of polymer-ligand and partition coefficient. Affinity partitioning should prove to be a useful complement to affinity chromatography in the purification of mixtures of proteins. Since cells and subcellular particles may be purified with aqueous polymer two-phase systems, affinity partitioning might be applied to their fractionation by using polymer-ligands specific for unique surface receptors.
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PMID:Affinity partitioning. A method for purification of proteins using specific polymer-ligands in aqueous polymer two-phase systems. 111 12

The O157 antigenic determinant of Escherichia coli serotype O157:H7, an important bacterial pathogen, resides in the polysaccharide portion of its cellular lipopolysaccharide component which, from structural studies, was identified as a linear polymer of a repeating tetrasaccharide unit composed of D-glucose, L-fucose, 2-acetamido-2-deoxy-D-galactose, and 4-acetamido-4,6-dideoxy-D-mannose residues (1:1:1:1). Hybrid cells producing monoclonal antibodies against the E. coli O157 antigen were obtained by fusion of myeloma cells with lymphocytes from BALB/c mice immunized with killed E. coli O157:117 cells. Clones were selected for binding specificity with purified O polysaccharide. One monoclonal antibody used in direct slide agglutinations or in coagglutination reactions with Staphylococcus aureus Cowan 1 cells sensitized with the affinity column-purified antibody accurately detected all strains of E. coli O157 tested. This selected monoclonal antibody did not agglutinate E. coli strains such as E. coli O7 and E. coli O116 or other bacteria which are known to give positive agglutinations with conventional polyclonal E. coli antisera. These results indicate that the monoclonal antibody is a superior specific-typing reagent.
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PMID:Identification of Escherichia coli serotype O157 strains by using a monoclonal antibody. 306 62

In the present study we have investigated whether bovine erythrocytes (Eb) specifically sensitized with human polyclonal IgA1 (Eb-IgA1) are able to bind to resident adherent rat peritoneal cells (PM phi). Rat PM phi formed rosettes with Eb-IgA1 at room temperature and at 37 degrees. The formation of these rosettes could be blocked completely by excess human serum IgA or myeloma IgA1. In contrast, human IgG or rat IgG did not inhibit the formation of rosettes, whereas human polymeric myeloma IgA2 only partially inhibited rosette formation. Complete inhibition of rosette formation was also induced by rat monomeric and polymeric myeloma IgA, suggesting species interchangeability. Furthermore, rosette formation could be completely blocked in the presence of excess asialofetuin or D-galactose, while excess ovalbumin or D-mannose had no effect. These results suggest that the oligosaccharides in the hinge region of human IgA1 are involved in the binding of Eb-IgA1 to rat PM phi.
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PMID:Binding of human IgA1 to rat peritoneal macrophages. 339 40

The lectin-binding capacity of 96 normal human IgG, assessed by solid-phase radioimmunoassay, strikingly varied according to the lectin considered. Indeed, half of the IgG samples exhibited peanut agglutinin (PNA)- and pokeweed mitogen-specific binding capacities superior or equal to 4%, whereas less than 15% of IgG similarly bound to concanavalin A (Con A) and to phytohemagglutinin. The ability of those IgG to inhibit the Fc receptor (Fc-R) function of human monocytes, measured by a classical rosette assay, was inversely correlated to their binding ratios to PNA and Con A only. By affinity chromatography, three groups of IgG were separated: the IgG purified on agarose-PNA columns slightly reduced the Fc-R function (40-45% inhibition); the IgG purified on Sepharose-Con A columns exhibited the highest inhibitory properties (80-85% inhibition); the IgG that did not bind to PNA and Con A columns possessed intermediate inhibitory properties (65-70% inhibition). The different effect of IgG on Fc receptors was conserved when monocytes were first treated by trypsin and was unrelated to their specific binding to human monocytes, to their subclasses, and to their C1q- or protein A-binding capacities. Incubation of monocytes with D-galactose (10 mM) significantly improved their capacity to form IgG rosettes, whereas their incubation with D-mannose (10 mM) significantly reduced the Fc-R function. Scatchard plots of 125I-IgG1 myeloma protein binding to monocytes were linear under basal conditions, as well as after a prior incubation of the cells with D-galactose or D-mannose. Monocytes bound about 16,000 molecules of IgG1 per cell in each instance. In contrast, the mean association constant (Ka) for IgG1 binding was 2.59 +/- 0.50 X 10(8) M-1 under basal conditions, 4.4 +/- 0.75 X 10(8) M-1 after D-galactose incubation, and 1.35 +/- 0.50 X 10(8) M-1 after D-mannose incubation. These data suggest that the level of human monocyte Fc-R function blockade induced by human IgG depends mainly on the presence of "accessible" galactosyl or mannosyl residues in the Fc domain and that the modulation of the Fc-R function induced by these carbohydrates is due to a change in the affinity rather than in the number of single class of high-affinity binding sites.
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PMID:The spontaneous ability of normal human IgG to inhibit the Fc receptors of normal human monocytes is related to their binding capacity to lectins. 362 80

The antiprotozoal drug pentamidine can be toxic to islet cells in vivo and in vitro. Rat islets were exposed to pentamidine (mesylate and isethionate salts) and six other structurally related diamidines. The beta-cell response to arginine + theophylline was suppressed by pentamidine (10(-2) mmol/l) while the glucagon and somatostatin secretions persisted. All diamidines tested suppressed the beta-cell function, with a log-dose-response proportionality, the mesylate compound being more potent than pentamidine isethionate, and the lipophilic analogs more than the hydrosoluble diamidines. Electron microscopy revealed distinct morphological alterations in islets exposed to pentamidine, the intensity of these changes being dose-and time-dependent, and the beta cells more severely damaged than the non-beta cells. 51Cr-labelled islet cells and RIN 5 F cells consistently appeared more sensitive to pentamidine cytotoxicity than rat fibroblasts, myeloma cells and hepatocytes. The pentamidine-induced suppression of beta-cell function was not, in conditions tested, affected by the presence of nicotinamide and the hexose concentration in the medium. The kinetics of islet damage were slower than those of streptozotocin and alloxan-induced islet damage. The present study confirms that pentamidine is selectively toxic to islet beta cells, with some features distinct from the alloxan and streptozotocin toxicities to these cells. The mechanism of this process and its precipitating factors in vivo need clarification.
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PMID:Functional and morphological modifications induced in rat islets by pentamidine and other diamidines in vitro. 389 20

Cell suspensions of mouse plasma-cell tumour MOPC 315 secreting predominantly IgA (immunoglobulin A) monomer and dimer were incubated with radioactive leucine, mannose, galactose and fucose for various periods of time. The amounts of secreted and intracellular immunoglobulins were measured by co-precipitation with specific antibody, and the molecular species present were assessed by electrophoresis in polyacrylamide gels. Analysis of the secreted myeloma protein demonstrated that monomer and dimer IgA molecules are identical with respect to carbohydrate composition and rate of secretion. Within the cell, the myeloma protein is almost entirely accounted for by monomer units which either leave the cell as such or are polymerized with the addition of J chain close to the time of secretion. The results support the concept of a stepwise addition of carbohydrate residues to IgA immunoglobulin during the process of secretion. Similar patterns of carbohydrate assembly were found for the monomer or dimer molecules. Mannose residues are added at an early stage, whereas fucose is added close to the time of secretion. Galactose is also added early, but some may also be incorporated at a later stage. Control of IgA polymerization is considered unlikely to reflect regulation at the level of carbohydrate addition, and it is suggested that the critical controlling factor is the J chain.
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PMID:Biosynthesis of immunoglobulin A (IgA). Secretion and addition of carbohydrate to monomer and polymer forms of a mouse myeloma protein. 420 51

Incubation of mouse myeloma microsomes with GDP-[(14)C]mannose results in the biosynthesis of [(14)C]mannose phosphoryl dolichol [Baynes, J. W., Hsu, A.-F. & Heath, E. C. (1973) J. Biol. Chem. 248, 5693-5704] and a [(14)C]mannose- and N-acetylglucosamine (GlcNAc)-containing oligosaccharide derivative of dolichol. Thus, [(14)C]mannose phosphoryl dolichol and [(14)C]mannose-labeled oligosaccharide pyrophosphoryl dolichol were isolated from incubation mixtures by solubilization in 2% (w/v) Triton X-100 and the lipids were separated from small molecules by gel filtration fractionation. After removal of radioactive protein from the preparation, the two lipid derivatives were separated quantitatively by fractionation on a concanavalin A-Sepharose column; [(14)C]mannose phosphoryl dolichol was not retained by the affinity resin but [(14)C]mannose-oligosaccharide pyrophosphoryl dolichol adsorbed to the gel and was eluted with alpha-methylmannoside.[(14)C]Mannose-oligosaccharide pyrophosphoryl dolichol appeared to be homogeneous when fractionated on DEAE-cellulose and in several thin-layer chromatographic systems. Treatment of [(14)C]mannose oligosaccharide pyrophosphoryl dolichol with 10% (w/v) NH(4)OH at 100 degrees for 1 hr resulted in the formation of a water-soluble radioactive oligosaccharide phosphate which was isolated and characterized as [Man](5) --> [GlcNAc --> GlcNAc --> P. Incubation of [(14)C]mannose-oligosaccharide pyrophosphoryl dolichol with myeloma microsomal preparations results in the transfer, presumably, of the entire oligosaccharide to endogenous protein. Kinetic studies indicate that the dolichol derivatives serve as intermediates in the glycosylation of protein as follows: [Formula: see text]
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PMID:The role of a dolichol-oligosaccharide as an intermediate in glycoprotein biosynthesis. 452 13

Plasma cells obtained from the peripheral blood of a patient with multiple myeloma was incubated in serum and Krebs-Ringer bicarbonate buffer with (14)C-labeled glucose, acetate, and propionate. Glucose utilization by these cells amounted to 0.5 mumole per hr per 10(8) cells and was mainly via the Embden-Meyerhof pathway, and only 6% or less traversed the hexose monophosphate shunt. The presence of Krebs cycle activity was demonstrated by direct isolation of several labeled intermediates after incubation with either (14)C-acetate or (14)C-propionate. The distribution of (14)C in lactate, succinate, fumarate, malate, aspartate, and glutamate indicate a complete Krebs cycle. Acetate was metabolized via the Krebs cycle to the extent of 0.15 mumoles per hr per 10(8) cells, and the rate of propionate utilization was 0.17 mumoles per hr per 10(8) cells.
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PMID:Carbohydrate metabolism in leukocytes. VII. Metabolism of glucose, acetate, and propionate by human plasma cells. 602 50


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