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)

The amino acid sequence of the heavy-chain variable region of the crystallizable human myeloma protein Dob has been determined. This protein has previously been shown to have a deletion in the hinge region [Lopes, A. D., & Steiner, L. A. (1973) Fed. Proc., Fed. Am. Soc. Exp. Biol. 32, 1003; Steiner, L. A., & Lopes, A. D. (1979) Biochemistry (preceding paper in this issue)]. The complete sequence was established by analysis, in the automated sequenator, of the intact Fd' piece and of three large overlapping fragments prepared from Fd' by digestion with cyanogen bromide, by tryptic digestion of the citraconylated Fd', and by cleavage with hydroxylamine. Portions of the sequence were confirmed by examination of the amino acid composition and the partial sequence of a variety of small peptides obtained by enzymatic degradation. The Dob heavy-chain variable region appears to belong to the VHIII subgroup, but there are several unusual substitutions. Residue 45 in the Dob sequence is proline, although all other known heavy-chain sequences in man, mouse, rabbit, and guinea pig have leucine at this position. Positions 10 (aspartic acid), 68 (alanine), and 82 (leucine) in the Dob sequence are also atypical. There is no deleted segment in the variable region of the Dob heavy chain nor any abnormality in the variable-constant joining region. The hinge-region deletion appears to be the only gross structural anomaly in the Dob heavy chain.
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PMID:Amino acid sequence of the heavy-chain variable region of the crystallizable human myeloma protein Dob. 11 9

The effect of several derivatives of ureidosuccinic acid on the growth of Escherichia coli 387, Staphylococcus aureus strain 209 and its mutant UV-2, Sarcina lutea, Candida tropicalis and Neurospora crossa 9863 as pre-screening systems for antitumor activity was studied. It was found that dihydrazide of D,L-ureidosuccinic acid (DHUA) had a marked antibacterial activity. The inhibitory effect of DHUA on N. crassa could not be removed by aspartic acid, ureidosuccinic acid, dihydroorotic acid, orotic acid, uracil or cytosine. DHUA suppressed the growth of Myeloma P-8 by 38%, that of Sarcoma 180 by 12% and that of Yoshida sarcoma by 19%. No effect was found on the growth of Lymphosarcoma Pliss.
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PMID:Antibacterial and antitumor activity of some derivatives of ureidosuccinic acid. 13 12

The mRNA coding for the kappa-type constant region (C(kappa)) was purified from two clones derived from the MPC-11 mouse myeloma. This mRNA directs the cell-free synthesis of a C(kappa) precursor (molecular weight, about 15,000) in which an extra piece, 17 residues long, precedes the NH(2)-terminal residue (Ala(109)) of the C(kappa) region. The partial sequence of the extra piece is: Met-X-Thr-Asp-Thr-Leu-Leu-Leu-Trp-Val-Leu-Leu-Leu-Trp-Val-Pro-X- (X is unknown). Met(1) was shown to be the initiator methionine. The sequence of the C(kappa) extra piece is completely different from any known sequence preceding residue Ala(109) in whole light (L) chains, thus establishing that the C(kappa)-region mRNA could not have originated from mRNA coding for the whole L chain. The structural features of the C(kappa) extra piece (marked hydrophobicity, size, and a methionine at the NH(2)-terminus) are identical to those characteristic of the NH(2)-terminal extra piece linked to the variable (V) region of whole L-chain precursors. In addition, the C(kappa) extra piece and the extra piece linked to the V region of MOPC-321 L chain have 70% sequence homology. These findings can be explained by the two genes-one Ig chain hypothesis, if we assume that the DNA coding for the extra piece (xp-DNA) is a constitutive part of the V gene. According to this model, the C(kappa)-region mRNA could have originated from: (i) translocation of this V gene to the C gene, deletion of the entire mature V gene, and "end-to-end" repair of the remaining xp-DNA to the C gene; (ii) translocation to the C gene only of the xp-DNA portion of the V gene. Alternatively, we may assume that the xp-DNA is not covalently linked to the mature V gene at all times, as might be the case for the DNA of hypervariable regions presumed to be in episomes. This raises the intriguing speculation that the xp-DNA represents a third distinct gene, designated xp-gene. The presumed xp-gene may be involved in the regulation of gene transcription: when linked to the mature V gene it initiates a chain of events leading to whole L-chain mRNA formation; when attached to the C gene it leads to its transcription to provide the C-region mRNA.
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PMID:Independent expression of the gene coding for the constant domain of immunoglobulin light chain: evidence from sequence analyses of the precursor of the constant region polypeptide. 41 16

The specific binding of radiolabelled IgE to a tissue culture lymphoblastoid cell line (Wil-2WT) was confirmed. The binding of IgE and Hamburger's IgE-derived pentapeptide Asp-Ser-Asp-Pro-Arg (HEPP) to Wil-2WT cells and to human leucocytes was compared. HEPP inhibition of IgE binding to leucocytes averaged 24% but with Wil-2WT cells only 12% inhibition was observed with double the amount of HEPP. Using myeloma IgE to inhibit the binding of tritiated HEPP to leucocytes and Wil-2WT cells confirmed the specificity of the peptide binding as well as the greater affinity of HEPP for leucocytes (basophils) compared to Wil-2WT lymphoblastoid cells. Based upon the extent of binding and the maximum inhibition attainable with HEPP it is suggested that the receptors for IgE on Wil-2WT cells, basophilic leucocytes and mast cells are not identical but that they share specificities in common. A new hypothesis for the mechanism of action of HEPP is proposed.
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PMID:Inhibition of IgE binding to tissue culture cells and leucocytes by pentapeptide. 52 Oct 61

The digestion of human IgG1/K myeloma proteins with pepsin in the presence of 8 M-urea produces fragments that differ from those produced by aqueous peptic digestion, and from other characteristic immunoglobulin fragments. Fb'2, the larger urea/pepsin fragment, was previously shown to consist of the constant regions of the light chains, and the CH1 domains and hinge regions of the heavy chains. The smaller fragment, upFc, has now been characterized. After reduction, three peptides were released from fragment upFc. Amino acid sequencing, N- and C-terminal determinations and amino acid compositions have enabled these peptides to be identified as residues Ile-253 to Leu-306, residues Thr-307 to Asp-376 and residues Thr-411 to Gly-446 of the heavy chain. Fragment upFc therefore contains the entire Fc region, beginning at residue Ile-253, except for a 34-residue section from within the CH3-domain disulphide loop. Peptic digestion of IgG1/K proteins in 8M-urea therefore provides a method for isolating from gamma1 heavy chains five homogeneous peptides in good yield, which account for almost the entire constant region. Characterization of fragments Fb'2 and upFc has shown that the action of pepsin in urea is entirely different from that of aqueous pepsin. Two gamma1 heavy chains have been shown to differ in sequence at three positions from the sequence reported for protein Eu.
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PMID:Characterization of upFc, a fragment of human immunoglobulin G1 produced by pepsin in urea. 79 Dec 67

From collected data on variable region sequences of heavy chains of immunoglobulins, the probability of random associations of any two amino-acid residues in the complementarity-determining segments was computed, and pairs of residues occurring significantly more frequently than expected were selected by computer. Significant associations between Phe 32 and Tyr 33, Phe 32 and Glu 35, and Tyr 33 and Glu 35 were found in six proteins, all of which were mouse myeloma proteins which bound phosphorylcholine (= phosphocholine). From the x-ray structure of McPC603, Tyr 33 and Glu 35 are contacting residues; a seventh phosphorylcholine-binding mouse myeloma protein also contained Phe 32 and Tyr 33 but position 35 had only been determined as Glx and thus this position had not been selected. Met 34 occurred in all seven phosphorylcholine-binding myeoma proteins but was also present at this position in 29 other proteins and thus was not selected; it is seen in the x-ray structure not to be a contacting residue. The role of Phe 32 is not obvious but it could have some conformational influence. A human phosphorylcholine-binding myeloma protien also had Phe, Tyr, and Met at positions 32, 33, and 34, but had Asp instead of Glu at position 35 and showed a lower binding constant. The ability to use sequence data to locate residues in complementarity-determing segments making contact with antigenic determinants and those playing essentially a structural role would contribute substantially to the understanding of antibody specificity.
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PMID:Attempts to locate residues in complementarity-determining regions of antibody combining sites that make contact with antigen. 106 Nov 62

That structural abnormalities may be responsible for nonamyloid immunoglobulin (Ig) light chain deposition disease (LCDD) is suggested by previous results of Ig biosynthesis studies, but this hypothesis was not documented at the molecular level. We report on the first complete primary sequence deduced from cDNA analysis of a kappa light chain responsible for LCDD associated with an apparently nonsecretory myeloma. Bone marrow myeloma cells contained intracellular kappa chains and no heavy chains by immunofluorescence. Kidney biopsy showed typical nonamyloid PAS-positive kappa chain deposits. SDS-PAGE analysis of material extracted from a kidney biopsy specimen and of Ig produced by the myeloma cells revealed kappa chains of abnormally high apparent molecular mass (30,000). Comparison of the NH2-terminal aminoacid sequence of the kappa chain deposited in the kidney and of the complete sequence of several identical kappa cDNA clones from bone marrow cells showed the identity of the tissue deposited and plasma cell kappa chain. The kappa mRNA had an overall normal structure and corresponded to the V kappa IV gene rearranged to J kappa 1 and followed by a normal constant exon of the Km(3) allotype. The variable sequence differed from the V kappa IV germline gene by nine point mutations, including an Asp----Asn substitution at position +70 resulting in a potential N-glycosylation site. In vitro biosynthesis experiments and treatment with N-glycosidase provided evidence for the intracellular glycosylation of the monoclonal kappa chain. The peculiar sequence and the glycosylation of a kappa chain of the rare V kappa IV subgroup might be responsible for structural abnormalities leading to tissue deposition.
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PMID:Structure of a monoclonal kappa chain of the V kappa IV subgroup in the kidney and plasma cells in light chain deposition disease. 190 72

Comparison of amino acid sequences of the alpha-chain fragment of human C4, C4d, has shown C4A- and C4B-specific sequences at residues 1101-1106 in which the aspartic acid-histidine substitution at position 1106 may be related to the amide and ester bond forming properties of these molecules. Peptides containing twelve amino acid residues of the C4A- or C4B-specific sequences were synthesized and injected into female Balb/c mice. Serum from 2 mice, one immunized with the C4A-specific peptide and the other with the C4B-specific peptide, gave strong isotype-specific responses in an enzyme-linked immunosorbent assay against affinity-purified C4A3 and C4B2B1. Spleen cells from these mice were fused with the mouse myeloma SP2/0-Ag 14, and two cloned cell lines, AII-1 and BII-1, were established from hybrids. Enzyme-linked immunosorbent assay and western blotting of monoclonal antibodies AII-1 and BII-1 show that the former reacts with the C4A but not with the C4B alpha-chain and the latter with C4B but not with the C4A alpha-chain. Furthermore, immunoblotting of C4 allelic variants showed that AII-1 reacted with all C4A allotypes tested, including A6, A4, A3 and A2, whereas BII-1 reacted with all C4B allotypes tested, including B5, B3, B2, and B1.
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PMID:Monoclonal antipeptide antibodies against amino acid residues 1101-1106 of human C4 distinguish C4A from C4B. 204 34

DNA from 161 patients with various forms of hematologic malignancies were investigated for mutations in exons 1 and 2 of the N-RAS, K-RAS and Ha-RAS gene by direct sequencing of DNA amplified in vitro by the polymerase chain reaction. Mutations involving either codons 11, 12, or 13 of the N-RAS gene were identified in 18 of the 161 patients. The relative frequencies of N-RAS gene mutations in these hematologic disorders was as follows: acute myelogenous leukemia (AML), 15%; acute lymphoblastic leukemia (ALL), 14%; myelodysplastic syndromes, 24%; and myeloid and lymphoid blast crisis of chronic myelogenous leukemia (CML), 3%. No correlation was observed between the presence of mutations and cytologic features or immunophenotype of these malignancies. Mutations involving codons 12 or 13 were equally prevalent, with a glycine to aspartic acid substitution being the most frequently encountered change. A single T-ALL case had a codon 11 mutation resulting in substitution of alanine with threonine. We failed to find mutations in exons 1 and 2 of the K-RAS or Ha-RAS genes in any case except a single AML with a mutation in codon 61 of the K-RAS gene. Also, no mutations were identified in chronic phase of CML, chronic lymphocytic leukemia. Ph1 positive ALL, non-Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma. These results indicate that RAS mutations, especially those involving exon 1 of the N-RAS gene, are frequent only in a subset of hematologic malignancies.
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PMID:The pattern of mutational involvement of RAS genes in human hematologic malignancies determined by DNA amplification and direct sequencing. 218 88

The specificities of the combining sites of 19 mouse monoclonal antibodies to dextran B1355S have been characterized immunochemically by quantitative precipitin and precipitin inhibition assays; association constants for B1355S were determined by affinity gel electrophoresis. Cross-reactive and individual idiotypes related to the BALB/c B1355S-binding myeloma proteins MOPC104E [IdI(MOPC104E)] and J558 [IdI(J558)], determined by a radioimmunoassay, and heavy-chain variable-region sequences, are presented. Antibodies to B1355S are "alpha (1----3) alpha (1----6)-specific" as determined by precipitin and precipitin inhibition assays with dextrans and oligosaccharides, respectively, containing alternating alpha (1----3) alpha (1----6) linkages compared with oligosaccharides composed solely of alpha (1----3) or alpha (1----6) linkages; all antibodies have low association constants (less than or equal to 10(5) ml/g). However, there is also considerable diversity among the proteins as seen in the five groups of different patterns of reactivity with numerous dextrans having different structures, and the variability in affinity even among antibodies showing the same fine specificity by precipitin assay. There is little observable correlation of heavy-chain variable-region amino-acid sequence with specificity or affinity; however, all proteins having D-region amino acids Tyr,Asp at positions 96,97 express the MOPC104E individual idiotype and belong to precipitin specificity group 5, the group most cross-reactive with numerous dextrans, whereas those proteins having the J558 individual idiotype, Arg,Tyr or Asn,Tyr at 96,97 are found in all five precipitin groups.
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PMID:Immunochemical studies of mouse monoclonal antibodies to dextran B1355S--II. Combining site specificity, sequence, idiotype and affinity. 242 50


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