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)

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

The growth of myeloma cells in Leibovitz medium supplemented with 20% serum was limited by the depletion of glutamine. A simple modification of the Leibovitz medium by increasing the concentrations of glutamine, lysine, isoleucine, leucine, sodium pyruvate, galactose, and vitamins resulted in over 100% increase in cell growth yield. The total myeloma protein produced by the cells was increased by approximately 90% in modified Leibovitz media. Analysis of spent culture media for 19 amino acids showed that the concentrations of 8 amino acids were reduced; those of 5 amino acids were increased and the other 6 did not change significantly.
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PMID:Amino acid metabolism of myeloma cells in culture. 96 31

A reagent made of zinc sulphate (0-08 M) in a 0-4 M sodium salicylate solution at pH 7-3 precipitated most of the IgG when a small volume of human serum was added. Sera with normal IgG levels or polyclonal hyperglobulinaemia showed a close correlation between total IgG and zinc-precipitated IgG (r = + 0-95). In clinical material, not including IgG myeloma, zinc-soluble IgG varied between 0 and 6 mg/ml and was independent of the IgG serum concentration. In 31 normal subjects the average IgG concentration, as determined by the Technicon immunonephelometric method, was 10-2 +/- 1-7 mg/ml for total IgG and 2-2 +/- 1-0 mg/ml for the soluble fraction. Among 173 sera, including 24 from cord blood, 16 from pregnant women, and 133 from patients with miscellaneous diseases, no pathological conditions except three cases of IgG myeloma were found with a zinc-soluble IgG definitely above the normal values; zinc-soluble IgG levels were often low in patients with hyperglobulinaemia, and the difference was highly significant in liver disease. kappa and gamma light chains as well as the four IgG-Hp chain subclasses were found in both zinc-soluble fractions of normal IgG. A study of myeloma monoclonal IgG showed that globulins of classes 1, 3, and 4 could be either soluble or insoluble in the zinc reagent. One, G2, was mainly insoluble. Hexose and antistreptolysin contents per milligram normal IgG were not significantly different in either fraction. It is suggested that zinc-soluble IgG consists of the recently synthesized molecules, the zinc-solubility of which has not yet been decreased by protein association, lipid interaction, antigen binding, or enzymatic denaturation. Within this hypothesis, a low level of soluble IgG would mean either an increased precatabolic protein or a decreased synthesis.
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PMID:Clinical and immunochemical study of the serum IgG fraction not precipitated in a zinc-sodium salicylate reagent. 100 43

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

Until five years ago, it was believed that the oligosaccharide chains of most, if not all, glycoproteins were assembled by the stepwise transfer of single sugar residues from their nucleotide derivatives to growing oligosaccharide chains attached to a polypeptide core. It is now becoming widely accepted that polyisoprenol-linked mono- and oligosaccharides function as activated glycosyl carriers in the biosynthesis of some glycoproteins in animal tissues. The lipophilic glycosyl carrier of monosaccharides is the phosphomonoester of dolichol, the C(80-100)-polyisoprenol, containing a saturated terminal isoprene unit. In this biosynthetic process, sugars are initially transferred to dolichol monophosphate from their nucleotide derivatives by membrane-associated glycosyltransferases. These dolichol-linked monosaccharides serve as glycosyl donors in the glycosylation of oligosaccharide phospholipids. It appears likely that dolichol is also the lipid moity of the oligosaccharide intermediates. Detailed enzymatic studies with oligosaccharide phospholipids formed by rat liver, a mouse myeloma tumor and hen oviduct have revealed that these intermediates function as oligosaccharide donors in the assembly of at least one class of glycoproteins. The exact nature of the glycoproteins glycosylated by lipid intermediates and the sub-cellular site(s) of this assembly process remain to be established. The possibility, that the mannose and GlcNAc-containing core found in many glycoproteins, is assembled at the lipid-level is now being investigated. At the current rate of progress in this area of research, the identity of the glycoproteins glycosylated via lipid intermediated and the subcellular site of this assmebly process will soon be known.
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PMID:Polyisoprenoid glycolipids involved in glycoprotein biosynthesis. 127 57

Four murine hybridoma clones secreting monoclonal antibodies (mAb) directed against lipopolysaccharide (LPS) antigen of S. newington, serogroup E1, were obtained after a fusion of spleen cells of mice immunized with formaldehyde-killed bacteria and mouse myeloma cells of the X63-Ag8.653 line. Antigen binding properties and specificity of the mAb were studied in bacterial agglutination tests, passive hemolysis and its inhibition, passive hemagglutination tests, passive hemolysis and its inhibition, passive hemagglutination and immunoenzyme tests (ELISA and immunoblotting). Three of the mAb (24E6, 29E1 and 45F6) were agglutinating and were active in all tests used, while mAb 31H12 did not agglutinate bacteria but revealed a high reactivity in the immunoenzyme reactions. It was found that the mAb reacted with LPS and Salmonella strains from serogroup E (E1, E2, E3 and E4) as well as from serogroups C (C1 and C4), F and S thus showing that the O3 antigen possesses more than one epitope, one of which is represented on the LPS antigens of the serovars from the cross-reacting groups mentioned. According to the known chemical the most probable recognized epitope consists of mannose with beta-linkage to the next monosaccharide residue in the LPS chain.
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PMID:Monoclonal antibodies directed to the O antigen of Salmonella serogroup E cross-react with lipopolysaccharides of Salmonella serogroups C, F and S. 128 92

The lectin peanut agglutinin (PNA) was used to study the surface carbohydrate expression of galactose beta 1, 3, N-acetylgalactosamine by normal and malignant hemopoietic cells. Immunostaining was performed using biotinylated PNA and a streptavidin-alkaline phosphatase staining technique on 78 patients. The study was undertaken to enlarge on previous reports of lectin binding to cells of hemopoietic origin and to establish the potential role of biotinylated PNA as a component of an immunotoxin for in vitro purging of bone marrow in patients with multiple myeloma. In normals only monocytes, macrophages, centroblasts and plasma cells showed reactivity. Of the hematological malignancies, all cases of multiple myeloma were positive and non-Hodgkin's lymphoma cases with a large cell component had positive centroblasts. Two of 5 cases of acute myelomonocytic leukemia, one case of chronic myelomonocytic leukemia and one case of pleomorphic T cell non-Hodgkin's lymphoma showed PNA positive neoplastic cells. The reactivity of biotinylated PNA with centroblasts and plasma cells suggests that it may be of potential value when linked to a streptavidin-ricin conjugate in the in vitro purging of bone marrow of patients with multiple myeloma prior to autologous bone marrow transplantation.
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PMID:Peanut agglutinin (lectin from Arachis hypogaea) binding to hemopoietic cells: an immunophenotypic study using a biotin streptavidin technique. 143 89

A gene encoding mouse-human chimeric secreted IgD was constructed using the rearranged murine variable region specific for the hapten dansyl and the genomic gene sequences for the constant region of the heavy (H) chain of human IgD. When expressed with the dansyl-specific chimeric light (L) chain, chimeric IgD specific for the hapten dansyl was synthesized and secreted as an H2L2 molecule. The pathway of assembly was H + L----HL----H2L2. The chimeric IgD heavy chain contains three N-linked carbohydrate moieties; one of these appears to be added co-translationally, and the other two appear to be added post-translationally. In secreted chimeric IgD some of the N-linked carbohydrate remains in the high mannose form. The chimeric IgD heavy chain also contains O-linked carbohydrate, which is added at the time of secretion. Inhibition of N-linked glycosylation with tunicamycin halts assembly at the HL half-molecule stage and prevents secretion. Like natural human IgD, the chimeric IgD binds to and upregulates the IgD receptor (IgD-R) on human peripheral blood T cells, and it is equivalent to human myeloma IgD in the competitive inhibition of rosette formation between IgD-R-bearing cells and IgD-coated Ox-RBC, Cross-linking by dansyl-BSA is needed for the chimeric IgD in soluble form to cause IgD-R upregulation.
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PMID:Structural and functional properties of mouse-human chimeric IgD. 163 67

Binding of biotinylated fetuin in a solid-phase assay served as activity assay for purification of calcyclin, the product of a cell growth-related cDNA with homologies to Ca(2+)-binding proteins. Asialofetuin failed to bind to calcyclin, emphasizing the importance of sialic acids. Binding of fetuin was most effectively reduced by N-glycolylneuraminic acid within a panel of mostly negatively charged sugars. Bovine submaxillary mucin and the ganglioside GM1, but not asialo-GM1, proved more effective than neoglycoproteins, carrying negatively charged carbohydrate moieties. Extension of N-acetyl-neuraminic acid to its lactosyl derivative increased its inhibitory potency. Among charge-free carbohydrate residues, only N-acetylglucosamine, lactose, and mannose, but not fucose, melibiose, or N-acetylgalactosamine affected fetuin binding, substantiating the inherent selectivity. Chemical modification with group-specific reagents revealed that lysine and arginine residues appear to be involved in ligand binding that is optimal in the presence of Ca2+, but not Zn2+ and stable up to 1 m NaCl. Biotinylation of calcyclin by modification of carboxyl groups facilitated performance of solid-phase assays with calcyclin in solution, yielding similar results with (neo)glycoproteins in relation to assays with immobilized calcyclin, thereby excluding an impact of binding to nitrocellulose on calcyclin's specificity. Subcellular fractionation disclosed the presence of fetuin-binding activity in all fractions, the specific activity decreasing from the nuclear to the particulate cytoplasmic fraction and the cytoplasmic supernatant. Affinity-purified antibodies were employed to detect high levels of calcyclin expression in acute lymphoblastic, myelogenous, and monocytic leukemia cell lines, but not in myeloma or lymphoblastoid cells. In comparison, most cells were nearly devoid of an O-acetylsialic acid-specific protein that is more abundant in various tissue types than calcyclin.
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PMID:Carbohydrate-binding specificity of calcyclin and its expression in human tissues and leukemic cells. 171 75

Balkan endemic nephropathy (BEN) is a tubulointerstitial disease characterized by increased-low-molecular-weight protein (LMWP), most notably, beta 2-microglobulin (beta 2m) excretion in urine. We previously demonstrated that two species of LMWPs, immunoglobulin light chains (LC) and recombinant alpha interferon (rIF), are toxic at proximal tubule cell membrane level. Myeloma LCs and rIF inhibit Na-dependent uptake of 14C-L-alanine and 14C-D-glucose by rat renal brush border membrane (BBM) vesicles at half-maximal inhibitory concentrations, IC50, ranging from 68 to 140 microM for LCs, and 5.4 to 18 nM for rIF. We further demonstrated that LCs bind to high-capacity, low-affinity sites on BBM with dissociation constants (Kd) ranging from 16 to 118 microM, a range similar to IC50s observed with the same LCs. Binding site occupancy is inversely related to alanine (r = -0.95, P less than 0.01), and glucose uptake (r = -0.96, P less than 0.01), implying that LC nephrotoxicity is determined by its binding to BBM. beta 2m shares behavioral and structural similarities with both LC and rIF. Preliminary studies in our laboratory showed that unlabeled LCs compete for the same binding sites on BBM with beta 2m. These observations confirm that all LMWP, including beta 2m, are potentially nephrotoxic. Thus, the characteristic beta 2-microglobulinuria of BEN may be more than a consequence of tubular dysfunction, and may play a pathogenetic role.
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PMID:Possible pathogenetic role of low-molecular-weight proteins in Balkan nephropathy. 176 43


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