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)

Affinity chromatography of IgG on protein A-Sepharose was used to isolate the human subclass IgG3 from normal serum and from a patient with multiple myeloma. The isolated material was purified by chromatography on Sephadex G-150 and characterized immunochemically. Ultracentrifugation studies gave so20,w values of about 6.80 for both normal and myeloma IgG3. Approximately 54 half-cystine residues per molecule of IgG3 were obtained as judged from amino acid analysis after performic acid oxidation of the proteins. Polyacrylamide gel electrophoresis in 0.1% sodium dodecyl sulfate of the isolated and reduced material resulted in two bands corresponding to molecular weights of approximately 23,000 and 56,000, respectively. The yield of normal human IgG3 represented 1%-2% of the total IgG.
 ...
PMID:Isolation of IgG3 from normal human sera and from a patient with multiple myeloma by using protein A-sepharose 4B. 81 76

Subclasses of the G-paraproteins were examined by the method of tryptic splitting of the sera. The fragments were identified in the immunoelectrophoresis with the antisera detecting the IgG, Fab-, Fc- and Fc1-fragments. It was revealed that for the IgGI most typical was formation of the Fc1-fragment continuously detected along with the Fab- and Fc-fragments; for the IgG1--retention of a considerable amount of unsplit protein; for the IgG3--formation of the Fab- and Fc-fragments, for the IgG4-- of the Fab-fragment alone. Analysis of 96 sera of the patients suffering from G-myeloma showed that 69 were referred to the IgGl, 19 - to the IgG2, 5 - to the IgG3, and 3 - to the IgG4. The method tested permitted successful identification of subclasses of the G-paraproteins, this serving as the necessary prerequisite for the choice of antigens and sorbents in the preparation of the subclass-specific antisera.
 ...
PMID:[Subclasses of immunoglobulin G. I. Determination of subclasses of G-paraproteins by the method of tryptic splitting]. 84 11

The specificity of the Fcgamma receptors in normal spleen and liver and in malignant tissues was studied using hemadsorption to cryostat sections. Indicator cells (EA) were sheep erythrocytes (E) sensitized with rabbit IgG antibody (A). The binding of EA to sections of normal and malignant tissues was inhibited by pooled IgG of human, rabbit, and guinea pig origin and by human IgG1, and IgG3, and IgG4 myeloma proteins. Heat-aggregated IgG inhibited the binding to sections of liver and some malignant tissues more effectively than monomeric IgG. The Fc fragments of IgG were also inhibitory, but not the F(ab')2, Fab', and Facb fragments. The inhibition obtained increased with decreasing amounts of A used for sensitization of E. The inhibitory activity of IgG was abolished after partial reduction and alkylation. No inhibition was obtained with IgG2, IgM, IgA, or albumin. E sensitized with Facb or F(ab')2 fragments of A did not bind to normal or malignant tissues. The specificity of the Fc receptors in normal spleen and liver and in malignant tissues is apparently very similar.
 ...
PMID:Specificity of Fcgamma receptors in human malignant tissue and normal lymphoreticular tissue. 99 50

Human myeloma proteins of the four IgG subclasses and their Fc, F(ab)2, and Fab fragments were tested for their ability to inhibit antibody-dependent human K lymphocyte-mediated cytotoxicity to chicken erythrocytes (CRBC) sensitized with specific rabbit antibodies. In addition, the adsorption of K cells onto glass bead columns coated with myeloma proteins was investigated. Myeloma proteins and their Fc fragments of all four subclasses inhibited K cell activity. However, there were wide variations within a given subclass and IgG2 and IgG4 proteins usually inhibited less than IgG1 and IgG3 proteins. Aggregation of the weakly inhibitory proteins with bis-diazotized benzidine increased their inhibitory effect. An IgG1 half-molecule with a deletion in the Cgamma3 domain was weakly inhibitory. Passage of lymphocytes through glass bead columns coated with IgG1 and IgG3 proteins removed K cell activity. In contrast, columns coated with IgG2 and IgG4 proteins, even when aggregated with BDB, failed to absorb K cells but removed significant numbers of SIg positive B lymphocytes. An enhancement of the antibody-dependent cytotoxicity was observed in 34% of the inhibition experiments in the presence of low concentrations of the weakly inhibitory proteins, usually IgG2 and IgG4. This enhancement occurred more frequently (53% of the experiments) with Fc fragments independent of the subclass. Moreover, addition of IgG2 and IgG4 but not IgG1 and IgC3 fragments induced a dose-dependent cytotoxicity to CRBC in the absence of anti-CRBC antibodies. These data indicate that IgG2 and IgG4 proteins have a lower affinity to K cells than IgG1 and IgG3 proteins and are compatible with an earlier hypothesis that proposes that more than one site on the Fc fragment can react with Fc receptors. The present results suggest in addition that there may be functionally different sites, one having a triggering function in K lymphocyte lysis that may be localized on the second constant domain and one being responsible for high affinity binding of IgG to cell receptors that is probably localized on the third constant domain.
 ...
PMID:Interaction of K lymphocytes with myeloma proteins of different IgG subclasses. 100 86

A peptide consisting of 10 amino acids derived from the CH3 region of human IgG was shown to bind to monocytes and to inhibit rosette formation of antibody-coated erythrocytes with human monocytes. Two myeloma proteins of the IgG1 and IgG3 subclass, both with known deletions in the CH2 region of the gamma chain, showed unimpaired ability to bind to monocytes. These experiments suggest that the isolated peptide represents the primary site of attachment of IgG to monocytes.
 ...
PMID:Localization of the IgG effector site for monocyte receptors. 105 14

The cytophilic activity of human myeloma proteins of different classes and subclasses for lymphocytes, monocytes, and neutrophils was investigated. Binding of both unaggregated immunoglobulins (Ig) and Ig aggregated with rabbit F(ab)2 anti-Fab fragment sera was determined. Lymphocytes bound unaggregated IgG1 and IgG3 proteins, but none of the proteins of the other classes. In contrast, after aggregation, IgG of all subclasses and IgE proteins bound to lymphocytes; aggregated proteins of the other classes did not bind. Monocytes bound unaggregated IgG1 and Ig3 better than Ig4 whereas the binding of proteins of other classes was insignificant. Neutrophils bound unaggregated IgG1 and IgG3 proteins and, in addition, IgA1, IgA2, secretory IgA, and IgG4 proteins. After aggregation, the neutrophils bound more Ig of all classes; however, the differences between the amounts bound remained similar to the amounts of unaggregated proteins. The native structure of the Ig molecule is necessary for the maintenance of complete activity, because Fc fragments bound less than intact Ig, and reduction and alkylation abolished cytophilia. The Fc receptors on all cell types tested showed no specificity for any of the respective cytophilic IgG subclasses; however, neutrophils appear to have separate receptors for IgG and IgA proteins.
 ...
PMID:Immunoglobulins cytophilic for human lymphocytes, monocytes, and neutrophils. 112 5

A study of the circular dichroic (CD) spectra of various fragments of human IgG3, including the isolated hinge region, Fh, has shown that the hinge region has a high degree of an unusual secondary structure, unique within immunoglobulin material recorded to date. This structure appears to be rigid and aperiodic throughout the hinge region and is compatible with a repeated amino acid sequence. The conformation of the isolated Fh fragment is the same as that of the bound hinge region; also, there is no substantial conformational interaction between the hinge region and the Fab or Fc fragments of human Igtg3. a comparison of the CD spectra of Fc and pFc fragments isolated from an IgG1 and an IgG3 myeloma protein has shown that subclass differences of amino acid sequence do not substantially alter the conformation of these fragments.
 ...
PMID:Conformation of the hinge region and various fragments of human IgG3. 114 26

A human anti-dextran serum, EAK, with IgG antibodies restricted to subclass IgG2, was tested for its capacity to induce lysis of dextran-coated chicken erythrocytes by normal human lymphocytes or monocytes. Another human anti-dextran serum, RGM, with most antibodies belonging to sublass IgG1, and a hyperimmune rabbit anti-dextran serum were used for reference. In lymphocyte-mediated erythrolysis, serum EAK gave rise to 51-Cr release varying from 20% to 80% in different experiments. The hyperimmune rabbit serum was 100 to 1000 times more active, whereas serum RGM was consistently negative. These results correlated well with the concentration of anti-dextran antibodies in these sera. In monocyte-mediated erythrolysis serum EAK had a somewhat higher titer than in lymphocyte-mediated lysis, and serum RGM had a weak but significant activity at low dilutions. Serum EAK also induced erythrophagocytosis by monocytes. Ultracentrifugation did not significantly decrease the inductive capacity of this serum. The results show that antibodies of human sublass IgG2 are efficient inducers of effector functions in both lymphocytic and monocytic cells. Myeloma proteins of the four IgG subclasses were tested for inhibitory capacity in lymphocyte- or monocyte-mediated erythrolysis. Either serum EAK or the rabbit reference serum was used for induction of erythrolysis. Individual myeloma proteins within and between the subclasses varied considerably in inhibitory power. However, whereas IgG1, IgG2, and IgG3 proteins inhibited lymphocyte-mediated erythrolysis induced by either type of antiserum, the two IgG4 proteins tested were essentially negative. These results suggest a lack of specificity of the Fc receptor for subclasses IgG1, IgG2, and IgG3 in both heterologous and homologous inhibition. In monocyte-mediated erythrolysis, IgG1 and IgG3 were strong inhibitors, whereas inhibition by IgG2 and IgG4 was weak and inconsistent. This pattern was seen regardless of whether and inducing antiserum was of rabbit or human origin. Similar results were obtained in monocyte-induced erythrophagocytosis induced by serum EAK. These and previous results suggest that effector cells of the lymphocytic (K cell) variety have Fc receptors different from those of monocytic cells. However, the basis for the differences observed in the inhibition tests remains to be elucidated.
 ...
PMID:Destruction of dextran-coated target cells by normal human lymphocytes and monocytes. Induction by a human anti-dextran serum with IgG antibodies restricted to the IgG2 subclass. 117 21

Digestion of human IgG by a new lysine-specific protease, isolated from the basidiomycete Armillaria mellea, produced Fc and Fab fragments similar to those produced by papain digestion of the same molecule. Digestion appeared to be restricted to a single cleavage point within the hinge region of the IgG molecule. Myeloma proteins of IgG1, IgG3 and IgG4 subclasses were found to be digested at an extremely rapid rate whereas IgG2 myeloma proteins appeared to be resistant to digestion by this enzyme.
 ...
PMID:Fragmentation of human IgG by a new protease isolated from the basidiomycete Armillaria mellea. 120 61

Isolated myeloma proteins of the four human IgG subclasses, aggregated by heat of bis-diazotized benzidine (BDB), induced aggregation of human platelets (Pl.A.) demonstrable by the sedimentation pattern test. With this sensitive technique, approximately 0-1 mug/ml of BDB-aggregated IgG1 and IgG3 could be detected whereas 200 to 1000 times higher concentrations of IgG2 and IgG4 were required for the Pl.A. reaction. The reaction pattern showed similarities with complement fixation tests.
 ...
PMID:Platelet aggregation by isolated and aggregated human IgG. 121 12


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