Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to determine the time in the intracellular life of immunoglobulin when the carbohydrate moieties are added. Plasma cells from a mouse myeloma tumor were exposed to glucosamine-(3)H (a "bridge" sugar), galactose-(3)H, or leucine-(3)H. With each of the above isotopes, the percentage of total radioactive immunoglobulin that has been secreted after different periods of labeling and the extent to which puromycin prevented incorporation into immunoglobulin were determined. The results indicate that both galactose and glucosamine (in its N-acetyl form) become covalently incorporated into immunoglobulin G late in its intracellular life and suggest that glucosamine is also added onto nascent polypeptide chains (i.e., on polyribosomes).
 ...
PMID:Immunoglobulin synthesis and secretion. I. Biosynthetic studies of the addition of the carbohydrate moieties. 545 11

The subcellular sites of synthesis and route of intracellular transfer of immunoglobulin G (IgG) have been investigated by electron microscope radioautography with precursors used for the polypeptide chain (leucine-(3)H) and for the carbohydrate moieties (galactose-(3)H and glucosamine-(3)H). For this purpose, plasma cells from a mouse myeloma tumor were labeled with appropriate precursors and the distribution of radioautographic grains was determined at the end of the labeling period and after varying times of incubation in unlabeled medium. The results indicated that the polypeptide backbone is synthesized in a region of the cell occupied by the rough endoplasmic reticulum (RER) and is transported from there to the region of the Golgi complex. Galactose is incorporated in IgG primarily at the level of the Golgi complex, whereas the incorporation of glucosamine appears to take place both in the RER and in the Golgi complex. From the Golgi complex, the completed IgG molecules reach the plasma membrane and are discharged extracellularly. The latter route of transport and the mechanism of discharge are not understood but may be mediated via smooth-surfaced vesicles.
 ...
PMID:Immunoglobulin synthesis and secretion. II. Radioautographic studies of sites of addition of carbohydrate moieties and intracellular transport. 546 Apr 63

Cells from an established line of Burkitt's lymphoma (Daudi) and a mouse myeloma (P(3)K) were pulse-labeled in vitro with (3)H-leucine, and immunoglobulin was immunologically precipitated from cell lysates and secretions. In contrast to P(3)K cells, Daudi cells synthesize a small amount of Ig which is not secreted. Subcellular fractionation experiments indicated that Ig of Daudi cells is synthesized on membrane-bound polyribosomes and enters the cisternae of the microsomes. Ig in the microsomes could be labeled with either (3)H-galactose or (3)H-fucose suggesting that transport proceeds to the Golgi complex. Additional evidence indicates that Ig molecules are transported to the plasma membrane but are not cleaved from the cell surface. These results together with other studies of Burkitt lymphoma cells suggest that the Daudi line may represent a clone of neoplastic cells derived from normal lymphocytes which synthesize but do not secrete Ig. Similarities between lymphoma cells and antigen-binding cells are discussed.
 ...
PMID:Immunoglobulin synthesis and secretion. VI. Synthesis and intracellular transport of immunoglobulin in nonsecretory lymphoma cells. 554 61

For a monomeric molecular weight of 180000 three type K macroglobulins (IgM) contained 6-deoxygalactose, mannose, galactose, 2-acetamido-2-deoxyglucose and N-acetylneuraminic acid in the molar proportions 5:38:11:27:7 for Row IgM, 5:31:9:21:7 for Sha IgM, and 5:29:11:26:8 for Tya IgM. The first two proteins were euglobulins whereas Tya IgM was a pseudoglobulin, and therefore the total content of carbohydrate does not appear to be related to the physicochemical properties of the proteins. The three proteins appeared to contain different numbers of oligosaccharide units, Row IgM having about ten units/monomer, and Sha IgM and Tya IgM about eight each. All three proteins had two types of oligosaccharide unit, which by analogy with an immunoglobulin A myeloma globulin were called Type 2 and Type 3 respectively. The Type 2 units had molecular weights equal to or greater than 2000 and contained 1 residue of 6-deoxygalactose, 3-4 of mannose, 1-2 of galactose, 3-4 of 2-acetamido-2-deoxyglucose and 0-2 of N-acetylneuraminic acid. The Type 3 units had molecular weights of less than 2000 and contained 0-1 residue of 6-deoxygalactose, 3-6 of mannose, 0-1 of galactose, 1-3 of 2-acetamido-2-deoxyglucose and no N-acetylneuraminic acid. Glycopeptides corresponding to the two types of unit varied in their aspartic acid content in that most of the Type 3 glycopeptides possessed only 1 residue of aspartic acid whereas most of the Type 2 glycopeptides had an average content greater than 1 residue.
 ...
PMID:A study of the carbohydrate present in three type K macroglobulins. 581 65

Two human IgM myeloma proteins, IgMWEA and IgMMAY, were found to react with agar and Klebsiella polysaccharides that contain pyruvylated D-galactose (DGal). Quantitative precipitin data and precipitin inhibition studies with methyl alpha- and beta-glycosides of 4,6-pyruvylated-D-galactose showed their combining sites to be different, although each was directed against the pyruvylated-D-Gal, one reacting most specifically with Klebsiella polysaccharides with terminal nonreducing beta-linked 2,4 pyruvylated-D-Gal, whereas the other reacted equally well with Klebsiella polysaccharides that contain 3,4 beta-linked and 4,6 alpha-linked terminal nonreducing pyruvylated-DGal. Inhibition studies showed that both sites are directed toward one of the two space isomers of 3,4- or 4,6-pyruvylated DGal, the form in which the methyl group of the pyruvate is equatorial, or endo, and its carboxyl group axial, or exo, to the plane of the acetal ring. Coprecipitation studies showed the combining site of IgMWEA to be located on an (Fab')2 fragment and not on the (Fc)5mu fragment. The monoclonal peak in the serum of IgMMAY was specifically precipitated by Klebsiella polysaccharide. Myeloma proteins with specificities of this type may occur with reasonable frequency in humans and may be a consequence of clonal expansion from inapparent infection, carrier states, or disease produced by various Klebsiella organisms.
 ...
PMID:Human monoclonal macroglobulins with specificity for Klebsiella K polysaccharides that contain 3,4-pyruvylated-D-galactose and 4,6-pyruvylated-D-galactose. 615 53

The immunochemical specificity of the combining sites of murine myeloma protein CAL20 TEPC1035 was studied by quantitative precipitin and precipitin inhibition assays. Myeloma protein CAL20 TEPC1035 precipitated with only three dextrans, B1355S4, B1498S, and B1501S, with high proportions of alpha(1 leads to 3) linkages, but not with any other dextrans, glycogen, and pullulan. Inhibition tests with various sugars show that the combining site of myeloma protein CAL20 TEPC1035 is most complementary to panose, a trisaccharide DGlc alpha(1 leads to 6)DGlc alpha(1 leads to 4)DGlc. Panose was 3.3 times more potent than a tetrasaccharide DGlc alpha(1 leads to 6)DGlc alpha(1 leads to 4)DGlc alpha(1 leads to 4)DGlc and 8, 23, 42, > 42 times more active than maltose, nigerose, isomaltose, and kojibiose, respectively. These findings were paralleled by their binding properties as determined by affinity electrophoresis. The association constants (Ka) of these three dextrans to myeloma protein CAL20 TEPC1035 ranged from 3.8 X 10(3) ml/g to 5.02 X 10(3) ml/g. The association constant of inhibitor (Kia) of panose was 8.19 X 10(3) M-1. Myeloma protein CAL20 TEPC1035 is an antidextran with specificity different from those of other murine myeloma antidextrans and from human antidextrans reported previously and its combining site size is at least as large as a trisaccharide. The binding constant of methyl alpha-D-glucoside (7.2 X 10(2)) was 73% of that of panose and comparable to that of myeloma protein W3129 (9.4 X 10(2)) with a cavity-type site and 600 times lower (1.6 X 10(0)) for QUPC52 with a groove type site, indicating that the terminal nonreducing residue is held in a cavity. Inhibition data with various alpha(1 leads to 4)-linked oligosaccharides also indicate that the internal portions of these inhibitors may react directly with a portion of the combining site. These findings suggest that myeloma antidextran CAL20 TEPC1035 has a partial cavity-type combining site in which the terminal nonreducing dGlc alpha(1 leads to 6) moiety is held in a cavity with the other two sugars forming a groove. However, oligosaccharides with one or more alternating [leads to 3DGlc alpha(1 leads to 6)DGlc alpha(1 leads to 3)DGlcl leads to] units with and without terminal nonreducing DGlc alpha(1 leads to 6) or DGLc alpha(1 leads to 3) side chains remain to be tested to determine whether structures known to be present in the three dextrans which precipitate CAL20 TEPC1035 may not prove to be more active than panose.
 ...
PMID:Immunochemical specificity of the combining site of murine myeloma protein CAL20 TEPC1035 reactive with dextrans. 616 Dec 5

A myeloma protein in ascitic fluid from BALB/c mice bearing W3129 plasma cell tumors was isolated by affinity chromatography. This protein exhibits anti-dextran activity and has been obtained in highly purified form by selective adsorption on isomaltosyl-Sepharose and elution with isomaltose solution. The isomaltosyl-Sepharose was synthesized from maltose, p-aminophenyl glucoside and cyanogen bromide-activated Sepharose by a new procedure utilizing glucosyltransferase and chemical coupling reactions. Results of gel electrophoresis, isoelectrofocusing and agar diffusion experiments showed that the purified myeloma protein consisted of 6 isomeric proteins with each isomer possessing anti-dextran activity. Data from hapten inhibition studies were interpreted to show that the W3129 myeloma protein combines with terminal isomaltosyl units of branched dextrans and oligosaccharides.
 ...
PMID:The isolation and characterization of a mouse myeloma protein with anti-dextran activity. 618 73

We have studied the specificities of two human monoclonal, IgM containing sera, s/IgMMAC and s/IgMFIS, from patients with polyneuropathy. s/IgMMAC precipitates only with chondroitin sulfate C and not with A and B whereas s/IgMFIS is precipitated by chondroitins A, B (dermatan sulfate), and C. Inhibition assays using 2-acetamido-2-deoxy-3-O-(4-deoxy-beta-L-threo-hex-4-enopyranosyluroni c acid)-D-galactose and its 6- and 4-sulfate derivatives showed that the disaccharide 6-sulfate was the best inhibitor of precipitation of s/IgMMAC by chondroitin sulfate C, and the disaccharide 4-sulfate the best inhibitor of precipitation of s/IgMFIS by either chondroitin sulfates C or B. The nonsulfated disaccharide was a good inhibitor in each instance. D-Glucose 6-sulfate, Na2SO4, several sugar phosphates, and phosphate buffer also inhibited but to different extents with the s/IgMMAC and s/IgMFIS. All studies were carried out in 0.15M NaCl. The data indicate that both monoclonal proteins are antibodies comparable to the phosphorylcholine-binding myeloma proteins, and that the reactions show specificities above and beyond charge effects. The relation of various cross-reacting macromolecules to the monoclonal antibody was studied by diffusion in gels.
 ...
PMID:Immunochemical characterization of the specificities of two human monoclonal IgM's reacting with chondroitin sulfates. 620 47

The hyalin material in massive cutaneous hyalinosis, a disease characterized by extensive tumorous periodic acid-Schiff-(PAS) positive extracellular cutaneous deposits, has been elucidated by biochemical and immunologic methods. Three major components were found: kappa light chains, a mannose-rich glycoprotein, and type I collagen. Trace amounts of fibrinogen, fibronectin, laminin, IgG, pregnancy-specific glycoprotein, albumin, and keratan sulfate, but not keratin, were also present. The kappa light chains were monoclonal, cryoprecipiting, and more basic than the kappa chains from two myeloma patients. The glycoprotein, which could not be identified as any known glycoprotein, had an apparent molecular weight of 90,000 D. Amino acid analysis showed that glutamic acid, aspartic acid, leucine, and threonine were abundant, whereas hydroxyproline, hydroxylysine, and sulfhydryl amino acids were absent. The carbohydrate content of the protein was approximately 20%. The major monosaccharides were mannose and N-acetylglucosamine. Galactose, N-acetylneuraminic acid and fucose also were present. The third major component of the hyalin material was identified as type I collagen. A humoral immune response to the storage material was found: the patient's serum contained IgM and IgG class antibodies against the mannosylglycoprotein (90 kD glycoprotein) and against type I collagen.
 ...
PMID:Massive cutaneous hyalinosis. Identification of the hyalin material as monoclonal kappa light chains, adhesive 90 kD glycoprotein, and type I collagen. 620 74

Two monoclonal antibodies (KH-1 and KH-2) against a transplanted fibrosarcoma (KMT-17) in WKA rats were produced by fusing a mouse myeloma (P3-X63-Ag8.653) with spleen cells from syngeneic rats hyperimmunized with KMT-17. Both antibodies showed complement-dependent cytotoxicity against KMT-17. By absorption of cytotoxicity, KH-1 reacted with homologous tumor, other syngeneic fibrosarcomas (KMT-80 and KMT-75), and lung and kidney from normal rats. However, KH-2 reacted with many kinds of tumors and various normal tissues. Antigen specificity was tested by complement fixation and/or solid-phase radioimmunoassay using glycolipids isolated from KMT-17 cells and authentic glycolipids. KH-1 reacted with globotriglycosyl ceramide which was not detected on KMT-17 cells and in cross-reacted weakly with IV3-alpha-galactosyl-lactoneotetraglycosyl ceramide, one of the major glycolipids of KMT-17. The immune reaction was inhibited by alpha-methyl-galactose. KH-2 reacted with lactosyl ceramide and lactoneotetraglycosyl ceramide. The reaction was more potently inhibited by lactose than by beta-methyl-galactose. Antibodies with similar specificity to either KH-1 or KH-2 were elevated in syngeneic rat sera after serial immunization with viable KMT-17 cells.
 ...
PMID:Carbohydrates as antigenic determinants of tumor-associated antigens recognized by monoclonal anti-tumor antibodies produced in a syngeneic system. 620 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>