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Biomedical subjects

J Melamed

Publications and source records attributed to J Melamed.

At least 73 records · Page 4Linked to original sources

Complement (C3b) interaction with the human granulocyte receptor: correlation of binding of fluid-phase radiolabeled ligand with histaminase release.

The interaction of C3b, the major cleavage product of C3, with its receptor on human granulocytes results in important biological functions, including phagocytosis, superoxide generation, and release of a variety of enzymes, including histaminase. We have determined the binding kinetics and isotherm of trypsin-generated fluid-phase dimeric C3b at both 0 degrees C and 37 degrees C using human polymorphonuclear leukocytes (PMN). At 37 degrees C the apparent number of receptors per cell was threefold greater than number at 0 degrees C (66,000 vs 21,000), and the affinity (Ka) was slightly less (3.5 X 10(7) M-1 vs 6 x 10(7) M-1). C3b dimer binding was specifically inhibited by a F(ab,)2 anti-C3b receptor antibody. C3b dimer induced histaminase release in a dose-dependent fashion at a concentration of 1 to 4 X 10(7) molecules/cell, whereas at lower concentrations a dose-dependent inhibition of opsonized zymosan-induced release was noted. These effects were independent of IgG. In contrast, C3b monomer failed to demonstrate measurable direct binding or to induce histaminase release. Histaminase release, however, did occur after incubation of PMN with affinity-linked monomer (anti-C3 F(ab')2-C3b complexes). Monovalent complexes did not affect release. Monomeric C3, C3c, and C3d were without effect; however, affinity-linked C3 and C3c did cause release.

Amine Oxidase (Copper-Containing)↗

Characterization of the human complement (c3b) receptor with a fluid phase C3b dimer.

The interaction of C3b receptor with C3b, the major cleavage product of C3, elicits important biologic functions, such as enhanced phagocytosis and release of cellular enzymes. We determined the binding kinetics and binding isotherm of C3b-receptor interaction by using human cells and fluid phase C3b generated by trypsin cleavage of purified native C3. 125I labeled C3b was separated into 2 molecular species, a dimer and a monomer by column chromatography. We found that dimeric C3b bound to human erythrocyte C3b receptors with an affinity that was more than 25 times that of the monomer. 125I dimeric C3b did not bind to sheep red blood cells, which lack the C3b receptor, nor to trypsinized or 2-mercaptoethanol treated normal human red blood cells, 2 methods for abrogating the immune adherence activity. Binding of 125I fluid phase C3b dimer to the C3b receptor was specific, saturable (about 90 ng of C3b dimer bound maximally per 1 X 10(9) red blood cells), reversible (in the presence of a 100-fold molar excess of unlabeled ligand), and of moderate affinity (Kd about 9.53 nM). The equilibrium binding constants were similar with the various cells tested. Binding was characterized by rapid on and off rates and did not exhibit ligand cooperativity. This specific interaction reached a steady state within 10 to 15 min at 0 degrees C; 50% of specifically bound ligand dissociated from its binding site on human red blood cells in approximately 1 min at 0 degrees C. The density of C3b receptors on human red blood cells, polymorphonuclear leukocytes, monocytes, and B lymphocyte-enriched preparations was 360, 20,000, 30,000, and 21,000 receptors/cell, respectively.

Animals↗

Possible nonspecific immunopotentiation by 2,4-dinitrochlorobenzene sensitization in patients with Hodgkin's disease.

Various immunological parameters were evaluated in untreated Hodgkin's patients before and after sensitization with dinitrochlorobenzene (DNCB). The ratio (r) of these parameters after/before DNCB sensitization for patients and second/first samples in the controls were calculated. There were significantly more patients in the r greater than 1.1 group for PHA and Con A responses and for peripheral blood T cell percentages. These data suggest that DNCB sensitization may have a nonspecific immunopotentiation effect.

Antibody Formation↗

Impairment of cell-mediated immunity in ectodermal dysplasia with aplastic anemia.

A case of ectodermal dysplasia and aplastic anemia is presented in which a cell-mediated immunodeficiency led to a fatal Pneumocystis carinii infection. Elevated levels of IgG, IgA and IgD were present with normal specific antibody titres. A deficient cell-mediated immunity was documented by low T cell numbers, poor in vitro mitogenic responses, negative skin tests and by the histologic finding at autopsy of thymic dysplasia.

Anemia, Aplastic↗

Comparative analysis of systemic immunological parameters in ulcerative colitis and idiopathic proctitis: effects of sulfasalazine in vivo and in vitro.

Comparative analysis of the systemic immunity revealed similarities between ulcerative colitis and idiopathic proctitis. In the active stage of both diseases, circulating complement receptor positive cells were increased whereas T-cell percentages and lymphocyte functions were decreased. In severe forms of ulcerative colitis and idiopathic proctitis circulating EAC-phagocytosing esterase positive cells, indicative of activated monocytes, were demonstrated. Successful treatment with salicylazosulfapyridine (SASP) reversed these immunological changes. Incubation of SASP and its metabolites with leucocytes from patients and control subjects, in concentrations similar to those demonstrated in sera from patients treated with SASP, did not alter the immunological changes.

Adult↗

Choriocarcinoma as a cause of thyrotoxicosis.

Three patients with choriocarcinoma had clinical and biochemical evidence of hyperthyroidism. Diminution in the thyrotoxicosis closely paralleled the fall in human chorionic gonadotrophin (hCG) levels. Three patients originally presented to internal medicine units as a problem of hemoptysis. Thyroid-stimulating hormone bioassay activity was demonstrated in the serum of all three patients prior to therapy. Recently evidence has been presented that hCG has intrinsic thyrotropic activity and that in conditions, such as hydatidiform mole, in which serum hCG levels are grossly elevated this thyrotropic activity can be sufficient to produce hyperthyroidism. Two of our cases supported the concept that hCG was also the substance with thyroid-stimulating activity in patients with choriocarcinoma. The third case left open the possibility that, in addition to the thyroid-stimulating activity of hCG, there may also be the production of a true ectopic thyroid-stimulating hormone (TSH). It is considered that the development of biochemical and clinical thyrotoxicosis in patients with choriocarcinoma depends upon the duration of the choriocarcinoma and the level of hCG.

Adult↗

Possible effect of maternal promethazine therapy on neonatal immunologic functions.

The effect of the administration of promethazine in the treatment of erythroblastosis fetalis was studied in four maternal-fetal pairs. The three infants exposed for a prolonged period of time had decreased neonatal number and function of T cells, and abnormal specific humoral immune responses. The possible role of promethazine in the induction of fetal immunoincompetence is discussed.

Antibodies↗