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)

The myeloma IgA protein produced by plasmacytoma XRPC-25, was isolated by affinity chromatography on dinitrophenyllysine-Sepharose. The affinity constant of the intact protein or its Fab' toward 2,4-dinitrophenyl-L-lysine (Dnp) was found to be 2.6 X 10(5) M-1. In order to prepare an Fv fragment (Hochman, J., Inbar, D., and Givol, D. (1973), Biochemistry 12, 1130) from this protein, the heavy and light chains were separated and the light chain was digested with trypsin at pH 8.2 to yield half a light chain. This digest was reassociated with the heavy chain and the recombinant was digested with papain at pH 5.7. Fractionation of this digest on a Sephadex G-75 column and Dnp-lysine-Sepharose resulted in the isolation of an Fv fragment which possesses one binding site for Dnplysine (Ka = 2.0 X 10(5) M-1). The active Fv fragment has a molecular weight of 23,400 and is composed of two peptide chains, each having a molecular weight of approximately 12,000. The N-terminal residues of these chains are aspartic and glutamic acids, which are also N-terminal in the heavy and light chains, indicating that the Fv is composed of VL and VH.
 ...
PMID:Preparation of Fv fragment from the mouse myeloma XRPC-25 immunoglobulin possessing anti-dinitrophenyl activity. 0 96

E myeloma protein, PS, was reduced in different concentrations of dithiothreitol (DTT) for 1 hr followed by alkylation with 14C-iodoacetamide. The affinity of the reduced-alkylated molecules for target cells was evaluated by their ability 1) to sensitize primate skin in a reversed P-K reaction, 2) to sensitize human basophils in a reversed-type histamine release and 3) to block passive sensitization with reaginic antibody. Antibody-epsilon0 antibody was employed for reversed type reactions to avoid participation of cell-bound normal IgE in the reactions. The sensitizing activity of IgE did not change following reduction in 1 mM DTT, which split inter-heavy-light chain disulfide bond. The activity of IgE significantly diminished after reduction in 2 mM DTT followed by alkylation. This treatment resulted in the cleavage of two intra-epsilon-chain disulfide bonds, which are present between the hinge and the Fd portion of the molecules. The reduced-alkylated protein was capable of sensitizing primate skin and human basophils, however, a much higher concentration of the reduced-alkylated protein than the native protein was required for passive sensitization. The optimal sensitization period for the reversed P-K reaction was 3 hr with the reduced-alkylated protein. The protein had the ability to block passive sensitization with reaginic antibody. The reduced-alkylated protein and the native protein were labeled with 125I, and binding of these proteins with human basophils was examined by autoradiography. The results showed that affinity of the reduced-alkylated protein for basophils was less than that of native protein. Since the disulfide bonds split by 2 mM DTT were not included in the Fc portion of the molecules, the Fc fragment was obtained from the reduced-alkylated protein and was tested for affinity for basophils. It was found that the Fc fragment had higher affinity than the reduced-alkylated protein. Recovery of the affinity by papain digestion strongly suggested that cleavage of disulfide bonds in the Fab portion of the molecules induced conformational changes in the Fc portion which is involved in binding to the target cells. Reduction of IgE with 10 mM DTT followed by alkylation resulted in cleavage of 5 disulfide bonds, which is accompanied by a loss of both sensitizing and blocking activities. The fifth disulfide bond which was cleaved by 10 mM DTT, but not by 2 mM DTT, appears to be an inter-heavy chain disulfide bond in the Fc portion of the epsilon-chains. Neither epsilon1 nor epsilon2 determinants in the Fc portion of epsilon-chains were degraded by this treatment.
 ...
PMID:Biologic significance of disulfide bonds in human IgE molecules. 4 81

Seven mouse myeloma proteins with specificity for phosphorylcholine (PC) were found to share a common antigenic determinant. This group of proteins contained members which differed in genetic origin, heavy chain class, kappa-chain subgroup, individual antigenic determinants and specificity for choline analogues. The cross-idiotypic determinant, VH-PC, was antigenically similar in each of the proteins and was associated with the variable portion of the heavy chain in the region of the antibody combining site. Further studies showed that an indistinguishable determinant was present on IgM anti-PC antibodies isolated from all strains of mice tested regardless of histocompatibility or heavy chain allotype. In view of the finding that this cross-idiotypic determinant was not found on antibodies or myeloma proteins which lacked specificity for PC, the data strongly suggest that a particular heavy chain variable region has been preserved in all mouse antibodies with specificity for PC.
 ...
PMID:Clonal nature of the immune response to phosphorylcholine (PC). V. Cross-idiotypic specificity among heavy chains of murine anti-PC antibodies and PC-binding myeloma proteins. 4 94

The structure and antigenic characteristics of a human k, IgG myeloma protein that formed half-molecules were analyzed. Most of the myeloma protein found in the patient's serum and urine consisted to two chain 4.3S half-molecules. A small amount of four chain 7S myeloma protein was, however, found in the serum and was apparently formed by the same clone of tumor cells. Polyacrylamide gel electrophoresis in 8 M urea and 1% sodium dodecyl sulfate and analytical ultracentrifugation in 6 M guanidine of the fully reduced and alkylated half-molecule indicated that this myeloma protein had a heavy chain of a smaller molecular weight (approximately 45,000) than that of normal gamma chains, Except for this apparent deletion, the heavy chain resembled gamma1 chains. The amino acid composition of the peptides containing the half-cysteine residues forming the interchain disulfide bonds, the glycopeptide of the Fc fragment and the COOH-terminal structure were similar if not identical with the analogous structures of gamma1 chains. No Fc fragment could be prepared because the Fc portion of the heavy chain of the myeloma protein was extremely susceptible to degradation with papain. After mild reduction and alkylation, the 7S myeloma protein dissociated into half-molecules, indicating a lack of noncovalent interactions in the Fc fragment that are present in all classes of human immunoglogulins and are responsible for the formation ofFc dimers. The half-molecule was antigenically deficient in the Fc fragment. It failed to precipitate with anti-Fc fragment antisera in double gel diffusion tests and inhibited a Fc-anti-Fc fragment binding reaction weakly and incompletely. The half-molecule and the 7S protein had the same genetic markers on the first and second homology region of the gamma chain. The half-molecule lacked, however, the corresponding markers on the third homology region, These findings suggest that this myeloma protein had a deletion in the gamma chain which was probably located in third homology region and was likely the structural abnormality responsible for the lack of noncovalent interaction in the Fc fragment and absence of most of the antigenic determinants characteristic of gamma chains.
 ...
PMID:Human myeloma IgG half-molecules. Structural and antigenic analyses,. 5 83

In this paper we report the structural basis for the nonexpression of G1m(3) and Km (1,2) allotypes in an IgG1 (kappa) human myeloma protein (protein LEC). Heavy and light chains spontaneously dissociate in sodium dodecyl sulfate polyacrylamide gels. Light chains appear to be covalently S-S bonded. Analysis of cysteine-containing peptides shows that the heavy chain of the IgG protein LEC has a deletion of residues 216-230, thus encompassing the entire hinge region. An arginine residue, characteristic of the G1m(3) marker is present at position 214. An alanine at position 153 and a leucine at position 191 of the light chain, characteristic of the Km (1, 2) allotypes, are present. It is likely that the double Km and Gm lack of expression is the result of the deletion. The genetic implications of the sequence of this protein are discussed.
 ...
PMID:Deletion of hinge region of human myeloma IgG1 molecule (protein LEC) associated with nonexpression of G1m (3) and Km (1, 2) allotypes. A possible genetic explanation at the DNA level. 6 77

Analysis of A/J antibody to phosphorylcholine (PC) revealed a striking degree of similarity to PC-binding myeloma proteins of BALB/c origin. By quantitative idiotypic analysis A/J anti-PC antibody was composed to antibodies bearing binding site idiotypic determinants indistinguishable from two different BALB/c myeloma proteins, T15 and M511. Idiotypic determinants of three other PC-binding proteins, W3207, M167, and M603 were not detected. Isoelectric focusing of the light chains verified the presence of antibodies similar to T15 and M511 and indicated the presence of a third antibody whose light chains had a pI identical to that of M603. When the sequence of A/J heavy chains were compared to the heavy chains of T15, M511, and M603, both the framework and first complementarity regions were identical in all cases. Sequences analysis of the light chains through part of the first complementarity region revealed three chains, one similar to each of the myeloma proteins T15, M603, and M167-M511. The latter two sequences differ by only a single amino acid (a single base substitution) in the first 23 residues, suggesting that the two light chains may be very similar if not identical. Thus, BALB/c and A/J mice which differ genetically at multiple loci including the heavy chain allotype complex locus show a remarkable preservation of their anti-PC antibodies. These results indicate that the genes encoding these antibodies are contained in the germ line.
 ...
PMID:Expression of equivalent clonotypes in BALB/c and A/J mice after immunization with phosphorylcholine. 6 19

A comparison of the clonal nature of the immune response to phosphorylcholine (PC) was made in nine different inbred mouse strains. Quantitative idiotypic analysis showed that anti-PC antibodies from each strain were composed of antibodies bearing binding-site idiotypic determinants indistinguishable from two different BALB/c myeloma proteins, T15 and M511. Idiotypic determinants of two other PC-binding proteins, M167 and M603, were not detected. Isoelectric focusing of the light (L) chains verified the presence of antibodies similar to T15 and M511 in each strain and indicated the presence of two additional antibodies, one of which has an L chain which cofocuses with M603. Fractionation of anti-PC antibody with anti-idiotypic antibody showed that immunoglobulins bearing T15 and M511 idiotypic determinants are separate and contain L chains that are unifore and resemble those of T15 and M511, respectively. Thus, these mice which differ genetically at multiple loci including the heavy chain allotype complex locus each possess, at least in part, an equivalent set of clonotypes specific for PC. This indicates that the genes encoding these antibodies must be contained in the germ line.
 ...
PMID:Uniformity in the clonal repertoire for the immune response to phosphorylcholine in mice. 6 40

The antigenic properties of the VH region of immunoglobulin heavy chains were studied by means of a fragment corresponding to the variable part of the heavy chain of an IgG3 myeloma protein (KUP) and an antiserum made against this fragment. By hemagglutination, hemagglutination inhibition, and immunofluorescence techniques, it was shown that the anti-VH antiserum detected three sets of antigens in the VH region, namely idiotypic antigens, VH subgroup-specific antigens, and VH domain-(framework) specific antigens. The VH fragment inhibited in a VHII subgroup-specific hemagglutination inhibition test system. The VH fragment was thus antigenically similar to the tvh region found in the intact molecules and the light chains were not needed to express the VH subgroup antigens or the VH framework antigens.
 ...
PMID:Antigenic studies of a VH fragment: demonstration of three sets of antigens, idiotypic, VH subgroup, and VH framework-specific antigens. 6 84

Murine myeloma immunoglobulin (IgA, K) J539, which shows enhanced tryptophanyl fluorescence on ligand binding, and S10, which shows reverse-sign changes in tryptophanyl fluorescence on ligand binding (RLIF, see below), have been reduced, alkylated, and dissociated into their light (L) and heavy (H) chains. Two hybrid recombinants, H10L539 and H539L10, have been prepared and the 7S material has been isolated by chromatography. The binding behavior of these recombinants was studied with a number of ligands. Both recombinants showed activity with beta(1 leads to 6) linked galactose ligands comparable to the native immunoglobulins. The ligand-induced fluorescence changes of the recombinants paralleled those of the heavy chain donor. For the recombinant H10L539, two different galactose-ligands caused fluorescence changes in opposite directions. It was quantitatively shown that binding of these ligands, nevertheless, took place in the same combining region. The idiotype of each recombinant resembled that of the heavy chain donor.
 ...
PMID:The formation of active hybrid immunoglobulins from the heavy and light chains of beta(1, 6) D-galactan binding murine myeloma IgA's S10 and J539. 7 Apr 73

The serum of a patient with multiple myeloma contained an IgG1 kappa monoclonal protein which existed in two molecular species: one with and one without inter-heavy chain covalent bonds, the latter dissociating into half molecules without reduction. The half molecules were present in the urine together with a kappa Bence-Jones protein. This peculiar protein was discovered because the serum and urinary IgG formed double percipitin lines when analysed by immunoelectrophoresis with an antiserum to gamma chains, the inner line being due to residual normal IgG. The isolated half molecule, as well as the major constituent of the 7 S IgG fraction, failed to precipitate with most antisera specific for the Fc fragment of IgG. The half molecule lacked the Gm(non a) marker and other antigenic determinants of the third constant region of gamma1 chains. No isotypic or allotypic antigenic determinant of another immunoglobulin class or subclass was detected. The molecular weights of the 7 S molecule, the half molecule and its covalently linked heavy and light chains were about normal, suggesting that they did not have a large deletion which could have caused the lack of interheavy chain covalent bonds. The hinge peptide appeared normal after high voltage electrophoresis of the peptic-tryptic digest of the reduced and alkylated half molecule. The carboxy-terminus of the heavy chain and the amino acid composition of the molecule were similar to those of IgG1 myeloma proteins. Two cysteinyl peptides of the CH3 domain showed on a diagonal peptidic map an electrophoretic mobility somewhat different from that of the corresponding peptides of an IgG1 myeloma protein. Another peculiar feature of this protein was the presence of galactosamine. Idiotypic determinants of the half molecule were present in the 7 S fraction, suggesting that the 7 S IgG molecules and the half molecules were derived from the same clone of tumour cells. Lack of material precluded further characterization of the structural abnormality--probably located in the third constant domain of the heavy chain--responsible for the absence of most antigenic determinants of the Fc region of IgG1 and for the formation of half molecules. This abnormality could be a small deletion undetectable by molecular weight measurements or an unidentified exchange of genetic material. Family members of the patient could not be studied in order to investigate whether this immunoglobulin abnormality reflected a minor genetic variant or a mutational event.
 ...
PMID:Immunochemical study of a human myeloma IgG1 half molecule. 8 30


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