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Biomedical subjects

M Mannik

Publications and source records attributed to M Mannik.

At least 109 records · Page 6Linked to original sources
PubMed1978

Nonimmunospecific protein-protein interactions of IgG: studies of the binding of IgG to IgG immunoadsorbents.

Nonimmunospecific interactions of IgG and IgG-agarose columns were systematically studied under varying conditions. Nonimmunospecific binding to the columns was primarily due to protein-protein interactions. These nonimmunospecific protein-protein interactions of IgG were enhanced with heat-induced or chemical aggregation of IgG, low pH, low ionic strength (at pH above 4), or low temperature. Conversely, this binding was decreased with proteolytic fragmentation of IgG, high ionic strength (at pH above 4), or temperatures above 4 degrees C. Chemical modification of IgG by acetylation, formalinization, carbamylation, or reaction with 1,2-cyclohexanedione significantly decreased these interactions. These observations suggest that above pH 4, ionic interactions caused the protein-protein binding. Below pH 4, hydrophobic interactions presumably play a major role. These results permit the development of rational methodology for avoiding nonimmunospecific protein-protein interactions in immunologic procedures for detection, isolation, or quantification of rheumatoid factors and other antibodies to IgG.

Antigen-Antibody Complex↗
PubMed1977

Bone marrow transplantation in patients with gold-induced marrow aplasia.

Aplastic anemia is a rare but usually fatal complication of gold salt therapy for rheumatoid arthritis. This report describes 3 patients who developed aplastic anemia while receiving gold salts, and a fourth patient who developed aplastic anemia after receiving gold and then cytotoxic agents. These patients failed to respond to conventional therapy for aplastic anemia and subsequently received bone marrow transplants from HLA-matched siblings. Engraftment occurred in all 4 patients. One patient is alive 2 years after transplantation, and 3 patients died of complications following transplantation.

Adult↗
PubMed1976

The disappearance kinetics of soluble immune complexes prepared with reduced and alkylated antibodies and with intact antibodies in mice.

Soluble immune complexes prepared with reduced and alkylated antibodies persisted longer in the circulation than complexes prepared with intact antibodies, when these were administered intravenously to mice. The disappearance of complexes with reduced and alkylated antibodies was delayed in part because the initial phase of vascular permeability was considerably less than that seen following the administration of complexes with intact antibodies. In addition, large complexes with lattice structure of more than two antigen and two antibody molecules persisted longer in the circulation after administration of complexes with reduced and alkylated antibodies than after administration of complexes with intact antibodies. Thus, the concentration of large latticed complexes with reduced and alkylated antibodies was significantly greater than the concentrations of large latticed complexes with intact antobodies at all observed times through 96 hours. The persistence of large latticed complexes with reduced and alkylated antibodies was associated with significantly decreased hepatic localization of complexes with reduced and alkylated antibodies compared to the hepatic localization of complexes with intact antibodies at 1, 4, 12, and 24 hours. The observations indicated that the removal of large latticed complexes from the circulation by the hepatic mononuclear phagocyte system was decreased when reduced and alkylated antibodies were used for the preparation of immune complexes. The persistence of large latticed complexes with reduced and alkylated antibodies in the circulation was associated with enhanced and prolonged presence of glomerular deposits of immune complexes, as reported in the accompanying article (Haakenstad AO, Striker GE, Mannik M: Lab Invest 35:293, 1976.

Alkylation↗
PubMed1976

The glomerular deposition of soluble immune complexes prepared with reduced and alkylated antibodies and with intact antibodies in mice.

The kidney localization and glomerular deposition of soluble immune complexes in mice were greater and more persistent following the intravenous administration of complexes prepared with reduced and alkylated antibodies than following the administration of complexes prepared with intact antibodies. The increased glomerular deposition following the administration of complexes prepared with reduced and alkylated antibodies was associated with the persistence of circulating complexes composed of more than two antigen and two antibody molecules (Haakenstad AO, Mannik M:Lab Invest 35:283, 1976). The deposition of immune complexes in glomeruli, as detected by immunofluorescence, appeared to precede the detection of mouse C3 in glomerular deposits following the administration of both preparations of complexes. The deposition of mouse C3 was more intense and persisted longer in mice receiving complexes containing reduced and alkylated antibodies than in mice receiving complexes containing intact antibodies. The ultrastructural studies indicated that both preparations of complexes initially localized as electron-dense material in endothelial cell fenestrae and in the subendothelial space of the glomerular capillary loops and subsequently accumulated in the mesangial matrix between mesangial cells. The material persisted in the mesangium of mice receiving complexes with reduced and alkylated antibodies, whereas it was removed from the mesangium of mice receiving complexes with intact antibodies. The mechanism for removal of complexes from the mesangial matrix was not defined, but it did not appear to occur through phagocytosis by the mesangial cell.

Alkylation↗
PubMed1975

Effect of cortisone on the disappearance kinetics and tissue localization of soluble immune complexes.

The effect of cortisone treatment on the disappearance kinetics, the hepatic uptake, and the glomerular deposition of i.v. administered, soluble immune complexes (HSAantiHSA) was examined in mice. An initial rapid disappearance of complexes from the circulation occurred after the injection of complexes into control mice, which was caused by increased vascular permeability. This phase was absent in the cortisone-treated group. The half life of complexes composed of more than two antigen and two antibody molecules (greater than Ag2Ab2)was prolonged from 1.93 hr in control mice to 4.71 hr in cortisone-treated mice while the half life of Ag2Ab2 complexes was unchanged (11.40 hr vs 12.04 hr). Although the clearance velocity of greater than Ag2Ab2 complexes was suppressed in cortisone-treated mice, the quantity of complexes specifically located in the liver at 1, 2, and 4 hr was not significantly different in the two groups. Persistence of circulating greater than Ag1Ab2 complexes was associated with enhanced and prolonged glomerular depostion of complexes in the cortisone-treated mice.

Animals↗
PubMed1975

The molecular basis of self-association of IgG-Rheumatoid factors.

The intermediate complexes, sedimenting between 19S and 6.6S components of normal serum on analytical ultracentrifugation, were purified from plasma of three patients with rheumatoid arthritis. Sequential gel filtration and removal of contaminants by agarose-antibody immunoadsorbents were employed for purification of these complexes. The isolated complexes from the three patients consisted of IgG with k and lambda light chains. Sedimentation equilibrium ultracentrifugation experiments showed that the isolated complexes underwent concentration-dependent self-association, whereby the smallest detectable molecular species had a molecular weight of 292,000. These IgG dimers were formed by self-association of IgG-rheumatoid factors, since nearly all F(ab) fragments, prepared from the isolated complexes by pepsin digestion, bound to normal IgG. The association constants for the interaction between normal IgG and one binding site of the F(ab) fragments were about 10-5 liters/mole. Since a cyclic structure with two antigen-antibody bonds was thought to form in the self-association of two IgG-rheumatoid factors, the association constant for dimer formation was calculated to be 10-10 liters/mole. The preferential self-association of IgG-rheumatoid factor was supported by the observation that monomeric normal human IgG did not replace the IgG-rheumatoid factor when the complexes were dissociated and reformed in the presence of excess normal IgG. The self-association of IgG-rheumatoid factors may be a general phenomenon in rheumatoid arthritis, as suggested by the observations of other investigators.

Antibody Specificity↗
PubMed1974

The molecular basis of self-association of antibodies to IgG (rheumatoid factors) in rheumatoid arthritis.

The serum and synovial fluid of many patients with rheumatoid arthritis contain immune complexes composed of immunoglobulin G (IgG). In this study such complexes from one patient are shown to be formed by self-association of IgG-antibodies to IgG (IgG-rheumatoid factors), so that each molecule serves as an antibody as well as an antigen. All F(ab')(2) and Fab' fragments derived from these complexes have antibody binding sites for normal IgG. Due to a high association constant in the formation of a cyclic complex by these antibodies, normal IgG is excluded as an antigen. These studies serve as a model for further elucidation of presence of similar immune complexes in the serum and synovial fluid of patients with rheumatoid arthritis.

Antibodies, Anti-Idiotypic↗