Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 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.
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PMID:Human myeloma IgG half-molecules. Structural and antigenic analyses,. 5 83

In order to explore structural differences between membrane and secreted immunoglobulins the buoyant densities of mouse immunoglobulin (Ig) heavy (H) chains were compared by isopycnic centrifugation in CsCl containing guanidine hydrochloride. The buoyant densities, under denaturing conditions, of mouse myeloma protein MOPC 21 IgG, MOPC 315 IgA and MOPC 104E IgM H chains were consistent with their carbohydrate contents. Mouse membrane IgM and MOPC 104E-secreted IgM H chains were of equal density. The buoyant densities of MOPC 104E-secreted IgM and spleen-cell-secreted IgM H chains were indistinguishable. The IgD-like membrane H chain was denser than membrane IgM H chain, and its carbohydrate content was calculated to be 15.5%. The resolution of the technique was sufficient to conclude that the apparent 1500 mol.wt. difference, as determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, between membrane and secreted IgM H chains was due to peptide rather than to carbohydrate. The results also imply that intact membrane IgM and IgD bind detergent and are thus integral membrane proteins.
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PMID:Density comparisons of heavy chains of membrane and secreted immunoglobulins of mouse. 11 45

The arrangement of disulfide bonds joining secretory component (SC) to the alpha chains in secretory IgA was studied by determining the molecular size of the principal fragments resulting from CNBr digestion of secretory dimeric Fc fragments from IgA (Fc)2alpha fragments). In vitro complexes formed by incubating 125I-free SC and myeloma 131I-(Fc)2alpha fragments were isolated by gel filtration and subsequently digested with cyanogen bromide. The CNBr digests of SC-(Fc)2alpha fragments were analyzed by gel filtration in 5 M guanidine. Two principal fragments were obtained, one containing a monomeric Fc fragment from IgA (Fcalpha) associated with SC (m.w. congruent to 110,000) and a second containing the second Fcalpha monomer (m.w. congruent to 50,000) from the dimeric SC-(Fc)2alpha. Similar results were obtained when secretory (Fc)2alpha fragments isolated from native secretory IgA dimer were subjected to CNBr digestion. The data indicate that SC is disulfide bonded to a single monomer subunit in secretory IgA dimer.
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PMID:Disulfide bonding of secretory component to a single monomer subunit in human secretory IgA. 40 58

The human myeloma protein Boh (gamma 2, lambda) was isolated and completely reduced and aminoethylated. The light chain was obtained by chromatography on Sephadex G-100 in 4 M guanidine HC1. The amino-terminal sequence on the blocked light chain could be determined by automatic sequence degradation after PCAase treatment. Twenty-one peptides were isolated from a tryptic digest and 12 peptides from a chymotryptic digest. The sequence determination on these peptides was performed by automatic sequencing methods. The light chain of Boh protein belongs to the lambda II subgroup. Unique substitutions have been found at position 8 (Arg) and position 62 (Tyr). Furthermore, the Boh light chain has six cysteine residues, the additional (sixth) cysteine being adjacent to the invariable intrachain-S-S linking cysteine at position 91. Sequence comparison of lambda II proteins reveals a high degree of homology emphasizing the biologic significance of the hypervariable region sequences;
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PMID:The primary structure of a human lambda II chain. 80 2

The conformational equilibria and the kinetics of the approach to equilibrium of an IgG1 myeloma (Wes) Fab fragment (SSFab) and its mildly reduced and S-carboxyamidomethylated derivative (RAFab) were studied as a function of guanidine hydrochloride concentration. The unimolecular denaturation of SSFab, the bimolecular denaturation of RAFab, and the denaturation of Wes L chain reported previously (Rowe, E. S., and Tanford, C., (1973), Biochemistry 12, 4822) are interpreted in terms of the domain structure and evaluated in terms of the thermodynamic stability of the protein and the covalent and noncovalent interactions among its subunits. The Fd-L interactions are found to be extremely strong and are maintained at concentrations of denaturant sufficient to denature the individual domains. It is shown that all of the data are consistent with a two region structure for Fab, one composed of the vL and vH domains, and the other composed of the cL and cH domains, so that there are two sites of noncovalent Fd-L interactions. One region, identified as the C region, is found to be 10(2)-10(4) times more stable than the other; this difference in stability is attributed largely to a stronger and more extensive interaction between the domains of this region. The kinetics of the approach to equilibrium are found to be extremely slow in the center of the transitions, requiring up to a week for equilibration for RAFab, and several months for SSFab. This unusual kinetic behavior is shown to be due to the strong Fd-L interaction under conditions where the monomeric domains are unstable.
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PMID:Dissociation and denaturation equilibria and kinetics of a homogeneous human immunoglobulin Fab fragment. 81 65

A recombinant human immunoglobulin epsilon-chain gene expression product (rFc epsilon) was compared with a human E myeloma protein in the affinity for epsilon-chain Fc fragment receptors (Fc epsilon R) on cultured human basophils. The association-dissociation kinetics of the rFc epsilon-Fc epsilon R interaction are indistinguishable from that of E myeloma protein, indicating that rFc epsilon and IgE have identical affinity for the receptors. The recombinant gene product sensitizes cultured basophils for anti-IgE-induced histamine release. A dose-response curve of histamine release indicates that the gene product is equally efficient in transducing the signal for degranulation as the natural IgE. Both the rFc epsilon and IgE lost the affinity for Fc epsilon R by heating at 56 degrees C. Upon renaturation by passage through a solution of 6 M guanidine hydrochloride, rFc epsilon recovered both the affinity for Fc epsilon R and the original CD spectra. On the other hand, renaturation of heat-denatured IgE largely restored optical activity above 250 nm but restored neither the affinity for Fc epsilon R nor the CD spectrum below 220 nm. The results suggest that either the amino acid sequence or the carbohydrate present in the myeloma protein, but not the rFc epsilon, may interfere with refolding of the receptor-binding structures.
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PMID:Biological properties of a recombinant human immunoglobulin epsilon-chain fragment. 243 Feb 85

A new case of IgE/K myeloma in a 38-year-old male is described. The clinical course, bone marrow picture and serum electrophoretic pattern were typical of multiple myeloma. Heating of the serum at 56 degrees C induced an irreversible gel formation or pyroglobulin that was isolated and proved to be identical to the IgE paraprotein, by biochemical and immunochemical methods. The thermoprecipitability was abolished by treatment with urea, sodium dodecyl sulphate and neutral salts and not inhibited by sugars, alcohols, 2-beta-mercaptoethanol and guanidine HCl. The association of an IgE myeloma protein with a pyroglobulin is a finding not previously reported in a myeloma of this class.
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PMID:IgE pyroglobulinemia in multiple myeloma. 318 Apr 63

The protein B of group B streptococci can bind in a nonimmune reaction to Ig of the IgG and IgM classes of various mammalian species (i.e., human, mouse, rabbit, and bovine). Protein B binding involves the Fc parts of both IgG and IgM molecules. Monoclonal or polyclonal IgG or IgM and the IgM-FC5 mu fragment of human myeloma protein combined with the protein B thereby inhibiting protein B-induced hemolysis in the CAMP reaction. The protein B/Ig complex can be dissociated with 1% Triton or guanidine-HCl (6 M). Mice infected intraperitoneally with sublethal doses of group B streptococci (GBS) and that received seven repeated intravenous injections of highly purified protein B during the first 9 h of infection developed fatal septicemia within 24 h with colony counts of up to 10(8) CFU/ml in the blood. Animals treated in the same way with either PBS or trypsinized protein B recovered. The protein B itself was not pathogenic when injected into healthy mice. Tissue sections of liver or spleen from mice infected with a lethal dose of GBS revealed the presence of protein B together with large numbers of cocci when stained by the peroxidase method using specific antibodies raised against purified protein B in the rabbit.
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PMID:Unspecific binding of group B streptococcal cocytolysin (CAMP factor) to immunoglobulins and its possible role in pathogenicity. 354 80

A monoclonal antibody to human Hageman factor (HF, factor XII) was derived from BALB/c mouse spleen cells fused with NS-1 mouse myeloma cells. This antibody, purified from ascites fluid, reacted with HF to inhibit the activation of HF, purified or in normal pooled plasma, as measured by a coagulation assay. The antibody did not inhibit the coagulant activity of activated HF. The antibody also inhibited the generation of amidolytic activity in HF-ellagic acid mixtures, but failed to inhibit the amidolytic properties of the carboxy-terminal fragment of HF (HFf). Amidolytic activity, absent in an HF-monoclonal antibody mixture, was generated upon treatment with insoluble trypsin. Monoclonal antibody, bound to CNBr Sepharose 4B gel (Pharmacia Fine Chemicals, Piscataway, NJ), reversibly bound HF in plasma or in buffer, without activating it. HF was then eluted with 4 mol/L guanidine HCI. The passage of 125I-labeled HF enzymatically cleaved by trypsin through a column of monoclonal antibody-CNBr Sepharose 4B gel resulted in flow-through of HFf with a molecular weight (mol wt) of 30,000 and HF fragments of mol wt 12,000. Elution with 4 mol/L guanidine HCI yielded several HF fragments (mol wt 80,000, 52,000, and 40,000) but not HFf. These data suggest that the single determinant recognized by the murine monoclonal antibody is not on HFf, but rather on the amino-terminal fragment thought to be involved in the binding activity of HF. The monoclonal anti-HF bound to CNBr-activated Sepharose 4B gel could be used to artificially deplete plasma samples of HF.
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PMID:A monoclonal antibody that inhibits activation of human Hageman factor (factor XII). 396 48

Protein 460 is a mouse myeloma gamma A(2) protein that competitively binds two small haptens, 2,4-epsilon-dinitrophenyl-L-lysine (Dnp-Lys) and 2-methyl-1:4-naphthaquinone thioglycollate (MenTG), to the antibody-combining region. The intact protein has a relatively inaccessible sulfhydryl group on each heavy chain. When it is substituted with a bulky reagent the binding affinity for MenTG decreases, while the binding of Dnp-Lys remains the same. Guanidine.HCl selectively reduces binding of Dnp-Lys; dimethylsulfoxide selectively reduces binding of MenTG. Papain digestion of protein 460 followed by column chromatography gave two fractions: one contained both binding activities and the other contained the sulfhydryl group. The affinity for Dnp-Lys of the first fraction is the same as that of the whole molecule, while affinity for MenTG is decreased. Since selective alteration of one or the other binding activity can occur in different ways, it seems likely that even though the haptens compete with each other, there is some spatial separation between the groups of contact amino-acid residues involved in the binding of these two haptens. These findings do not support the hypothesis that an immunoglobulin molecule carries combining sites complementary only to a single hapten or to a structurally related series of haptens, but rather suggests that the antibody-combining site may be a polyfunctional region capable of binding several structurally dissimilar haptens. We discuss a mechanism whereby polyfunctional combining sites can give rise to an antibody population (immune serum) that has a high degree of specificity to a single hapten.
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PMID:Contact regions for dinitrophenyl and menadione haptens in an immunoglobulin binding more than one antigen. 411 41


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