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)

It has been shown that epitopes reactive with one group of rabbit antibodies to human fibrinopeptide A (hFPA, A alpha 1-16) are included in its COOH-terminal region (A alpha 7-16). It was further established that Asp-7, Phe-8, and Arg-16 contribute to immunoreactivity and that intact fibrinogen and hFPA-containing fragments react poorly with such antibodies. The purpose of this investigation was to prepare a synthetic peptide corresponding to A alpha 7-16 and use it for generation of FPA-specific monoclonal antibodies (MoAbs). Such probes would allow for development of assays that could measure hFPA directly in plasma. In our approach, an ovalbumin-conjugate of the hFPA homologue served as immunogen. Mouse spleen cells were fused with the immunoglobulin nonsecretor myeloma (P3X63Ag8.653). A hybridoma (8C2-5) has been isolated that secretes an antibody (MoAb/8C2-5) with the following characteristics: (a) IgG1, kappa isotype; (b) equilibrium dissociation constant of 1.5 +/- 0.2 x 10(7) L/mol with the [125I]-labeled N-tyrosyl derivative of hFPA [( 125I] Tyr-hFPA) as ligand; (c) reacts with hFPA and dog FPA (dFPA) but not with the des Arg (A alpha 1-15) or shorter peptides; (d) does not react with intact fibrinogen or A alpha-chain of human or dog origin; (e) does not react with the elastase-generated hFPA-containing peptide A alpha 1-21. Enzyme-based immunoassays (EIAs) have been developed for measuring plasma hFPA levels in the range 3 x 10(-8) to 5 x 10(-7) mol/L. Since it has already been shown by a number of investigators that hFPA levels in patients with overt defibrination fall into this range, we propose that the MoAb/8C2-5-based assays may serve as useful clinical tools in screening patients at risk of thrombosis. The 8C2-5 antibody may also be helpful in studies dealing with congenital dysfibrinogenemias, particularly in identifying heterozygous propositi with amino acid substitutions at any position within the A alpha 7-16 region. Finally, due to its cross-reactivity with dFPA, assays using this antibody should also be valuable in the canine experimental thrombosis model studies.
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PMID:Use of a synthetic homologue of human fibrinopeptide A for production of a monoclonal antibody specific for the free peptide. 275 51

Immunoglobulin Fc-binding activity was detected by indirect immunofluorescence employing fluorochrome conjugated F(ab')2 antibody fragments on acetone-fixed cell cultures infected with herpes simplex virus type 1 (HSV-1). Using this method the Fc receptor-like activity seemed to be restricted to the IgG class of human immunoglobulins. While IgG1, IgG2, and IgG4 myeloma proteins bind to this putative Fc gamma receptor at a concentration of 0.002 mg/ml, IgG3 myeloma proteins were without activity at 0.1 mg/ml. The binding activity was associated with the Fc fragments of IgG, while the pFc' fragments of IgG appeared to be unable to bind in this assay system. The reactivity and specificity of the HSV-1 Fc receptor was independent of both the type of tissue culture cells used and the strain of HSV-1 inducing the Fc receptor-like activity. The HSV-1-induced Fc receptor has a similar specificity for human immunoglobulin class and subclasses as staphylococcal Protein A. However, these two Fc receptors exhibit at least one striking difference. The IgG3 G3m(st) protein which binds to Protein A does not bind to HSV-1-induced Fc receptor. A possible reaction site for the HSV-1 Fc receptor on IgG could be at or near Asp 276.
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PMID:Binding site and subclass specificity of the herpes simplex virus type 1-induced Fc receptor. 298 35

An IgGl(lambda) Mot myeloma protein showed a unique susceptibility toward papain digestion. The Fab fragment of Mot was more digestible with papain than the Fc fragment. This phenomenon was found to occur by unusual cleavage of the Fd fragment with papain. Determination of the complete primary structure of the V region of the H chain of Mot identified two papain cleavage sites in the second complementarity-determining region (CDR). Amino acid sequence of the cleavage sites was Ser(55)-Asp-Asp-Argdecrease-Thr-Thr-Tyr-Gly-Pro-Argdecrease- Ser-Gln- (decrease = cleavage site). In the vicinity of these cleavage sites, many hydrophilic and polar residues are present and the predicted secondary structure near these cleavage sites suggested that this region was exposed on the surface of the molecule, and that the unusual papain cleavage of the IgG Mot might be caused by a unique conformation of the molecule, making it highly susceptible to enzyme digestion.
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PMID:Amino acid sequence of the variable region of heavy chain in immunoglobulin (Mot) having unusual papain cleavage sites. 308 50

1. Peptide maps of Fc fragments or heavy chains of 36 G myeloma proteins and two "heavy chain disease" proteins belonging to the four gamma-chain subgroups revealed very striking similarities between them. However differences in a few peptides were noted. This was most pronounced for the Ge(gamma(2)d) subgroup which lacked three peptides characteristic of the other three subgroups. While Fc fragments from different proteins belonging to the same subgroup appeared very similar, minor differences in addition to those based on currently recognized Gm factors were occasionally noted. 2. Fc fragments from Gm(a+) We(gamma(2)b) proteins had a peptide previously shown to be characteristic of normal Gm(a+) gammaG-globulins. Fc fragments from Gm(a-) molecules belonging to the We(gamma(2)b), Vi(gamma(2)c), or Ne(gamma(2)a) subgroups, whether Gm(b+), Gm(f+), or Gm(-), had the peptide previously identified in Gm(b+f+) normal gammaG-globulin. This "non-a" peptide was absent in peptide maps from Gm(-) molecules of the Ge(gamma(2)d) subgroup which contained instead another peptide with the same electrophoretic mobility but migrating slightly further on chromatography. 3. Both the "a" and "non-a" peptides were pentapeptides having three amino acids in common, and differing in the other two. The "a" peptide contained one residue of lysine, aspartic acid, threonine, leucine, and glutamic acid. The "non-a" peptides prepared from Gm(b+), Gm(f+), and Gm(-) proteins were identical and contained one residue of lysine, threonine, and methionine sulfone, and two residues of glutamic acid. 4. Several possible mechanisms for the origin of these differences, and their possible role in serologic specificity are discussed.
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PMID:Structural studies of human gamma-G-myeloma proteins of different antigenic subgroups and genetic specificities. 416 48

The carbohydrate content of an A myeloma globulin was investigated. The carbohydrate content was found to be unchanged when the protein was isolated from the patient over a period of 18 months. The various polymeric forms of the protein contained similar proportions of carbohydrate. The A myeloma globulin contained approx. 2 residues of 6-deoxy-l-galactose (l-fucose), 14-15 of d-mannose, 12-13 of d-galactose, 12-13 of 2-acetamido-2-deoxy-d-glucose (N-acetyl-d-glucosamine), 6 of 2-acetamido-2-deoxy-d-galactose (N-acetyl-d-galactosamine) and 5 of N-acetylneuraminic acid (sialic acid), and these were distributed between six oligosaccharide units all of which were present on the heavy polypeptide chains. The oligosaccharide units showed two kinds of heterogeneity, which have been termed central and peripheral. Central heterogeneity was shown by the presence of three completely different core units, which had the following compositions: (1) 3 residues of d-galactose and 3 of 2-acetamido-2-deoxy-d-galactose, joined to protein by an O-glycosidic linkage between acetamidohexose and serine; (2) 3 residues of d-mannose, 2 of d-galactose and 3 of 2-acetamido-2-deoxy-d-glucose, joined to protein by an N-glycosidic linkage between acetamidohexose and aspartic acid; (3) 4 residues of d-mannose and 3 of 2-acetamido-2-deoxy-d-glucose with a linkage similar to that in (2). The core oligosaccharide units showed peripheral heterogeneity in the attachment of 6-deoxy-l-galactose, 2-acetamido-2-deoxy-d-glucose and N-acetylneuraminic acid. Tentative structures are proposed for these various types of oligosaccharide unit. Glycopeptides were isolated in which the sialic acid content exceeded that of d-galactose. Explanations are given for the electrophoretic mobility and staining characteristics of the various glycopeptides.
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PMID:Investigations on the oligosaccharide units of an A myeloma globulin. 417 99

Glycopeptides have been isolated from tryptic digests of kappa-type light chains separated from human myeloma proteins obtained from the serum of two patients, Car and Rai. The glycopeptides are derived from the variable region of the chain in both cases, but from different sections. On the basis of homology it is deduced that glycopeptide from Car, kappaI type, is derived from position 25-31 whereas that from Rai, kappaII type, is from position 62-77, their sequences being respectively Ala-Ser-Gln-Asn-Ile-Ser and Phe-Ser-Gly-Ser-Gly-Ser-Gly(Thr,Asp)Phe-Thr-Leu-Asx-Ile-Ser-Arg. The significance of the results is discussed in connexion with the nature of the attachment site of carbohydrate to protein.
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PMID:Glycopeptides from human kappa-chains. 511 28

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.
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PMID:A study of the carbohydrate present in three type K macroglobulins. 581 65

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.
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PMID:Massive cutaneous hyalinosis. Identification of the hyalin material as monoclonal kappa light chains, adhesive 90 kD glycoprotein, and type I collagen. 620 74

Phosphorus-31 nuclear magnetic resonance (NMR) studies on the two phosphorus nuclei of the phosphonium analogue (Me3P+CH2CH2OPO3(2-)) of phosphocholine are used to monitor the charged subsites in the phosphocholine-binding immunoglobulin A mouse myeloma M603. Comparison of the 270-MHz 1H NMR difference spectrum on addition of either this analogue or phosphocholine to M603 and the almost identical changes in the pKa values of the phosphate groups on binding to M603 confirm that the analogue is a good model for phosphocholine. The pKa of the phosphate groups is decreased by 0.5 unit on binding to M603, which is consistent with the phosphate group being hydrogen bonding to Tyr-33H and Arg-95L, as suggested from the X-ray structure, and also implies that the binding energies for the mono- and dianion are similar. The P+Me3 moiety is used to probe the electrostatic interactions in the choline subsite. Titration of the chemical shift of the phosphonium phosphorus reflects a group on the protein that has a pKa value of less than or equal to 5, which from the refined X-ray structure (D.R. Davies, personal communication) of the site is assigned to Asp-97L. The choline subsite is monitored by using 1H NMR difference spectra, which indicates that the subsite is highly aromatic as expected from the crystal structure that places Trp-107H and Tyr-100L in this subsite. The ring current interactions from these rings can account for the 1H NMR chemical shift data on choline.
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PMID:A combined proton and phosphorus-31 nuclear magnetic resonance investigation of the combining site of M603, a phosphocholine-binding myeloma protein. 629 93

The complete amino acid sequence of the variable region of Bence-Jones protein Mev. from a patient suffering from multiple myeloma and generalized amyloidosis is presented. The amino acid sequence of the Bence-Jones protein Mev. is related to other human kappa-immunoglobulin L-chains of subgroup I. With valine established in Position 191 of the constant region, it is of the Inv (3) allotype. Two types of the Bence-Jones protein Mev. were found, one beginning with the typical N-terminal aspartic acid, and another lacking the N-terminal tripeptide and commencing with methionine in Position 4. A unique insertion of glutamic acid after Position 95 was found in the Bence-Jones protein. This is the position where the V- and J-gene segments join. The J-region of Bence-Jones protein Mev. exhibits some marked differences to the five J-regions recently established by nucleic acid sequencing. This suggests, that there must be considerable polymorphism in human kappa-J-genes. The amyloid fibril protein from the same patient (A Mev.) has also been sequenced up to Position 27. It was found to be identical to the sequence of Bence-Jones protein Mev. commencing with aspartic acid. The molecular mass of the amyloid fibril protein was found to be between 11 000 and 12 000 Da as estimated by gelfiltration and dodecyl sulfate-polyacrylamide electrophoresis.
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PMID:Primary structure of the variable part of an amyloidogenic Bence-Jones Protein (Mev.). An unusual insertion in the third hypervariable region of a human kappa-immunoglobulin light chain. 681 13


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