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Biomedical subjects

J Leibowitch

Publications and source records attributed to J Leibowitch.

50 records · Page 3Linked to original sources
PubMed1980

The dense deposits disease of the renal basement membranes.

Dense-deposits disease is characterized by an original morphological aspect of the renal basement membranes which have an electron-dense appearance. The immunofluorescence studies showed C3 alone in kidney. Low serum C3 levels and the presence of C3 NF activity have been detected in this disease, demonstrating an activation of the complement alternative pathway. The observation of recurrence in transplanted kidneys contributed to establish the sequence of the morphological events and showed the dissociation between the serological complement profiles and the lesions. Although the nature of the dense deposits remains still unknown, the altered membranes are recognized by at least some anti-GBM antibodies.

Antigens↗
PubMed1980

Nephritic factor of the classical pathway of complement: immunoglobulin G autoantibody directed against the classical pathway C3 convetase enzyme.

A factor, functionally characterized by its capacity to stabilize the normally labile classical pathway C3-converting complex of the classical pathway of complement, has been isolated from the serum of one patient with a case of acute glomerulonephritis, subsequent to a cutaneous infection. The factor confers long-lived stabilization of classical pathway C3 convertase complexes formed both in the solid (sensitized sheep erythrocytes bearing activated C1 and the classical pathway C3 convertase) and fluid phase. The half-life of such stabilized C3-cleaving enzymes extended beyond several hours at 37 degrees C. The stabilizing activity was associated with a protein fraction immunochemically identified as immunoglobulin (Ig)G, a sizeable population of which exhibited a gamma chain of 60,000 daltons. The IgG-associated stabilizing activity was found to bind to the classical pathway C3 convertase enzyme via a fragment bearing the antigen-binding site of the molecule [F(ab)(2) and F(ab)]. Such binding was demonstrable for classical pathway and not for alternative pathway C3 convertase. Thus, the stabilizing factor behaves like an autoantibody to the C3-converting complex of the classical pathway of complement. The binding of the antibody to the enzyme affords protection of the latter against decay-degradation. By analogy with the nephritic factor of the alternative pathway situation where IgG autoantibodies specifically bind to alternative pathway C3 convertase enzymes and protect them from degradation, the functionally unusual IgG in our patient was designated as the nephritic factor of the classical pathway. Indirect evidence suggests that nephritic factor of the classical pathway-IgG might be of the IgG3 subclass.

Adult↗
PubMed1980

In vitro characteristics on human lymphocyte functions of a new immunomodulatory agent, a cyclic peptide, cyclomunine.

Cyclomunine, a cyclic peptide extracted from Fusarium equisiti, inhibits responses of human lymphocytes to mitogens, soluble antigens and allogeneic cells and the proliferation of lymphoblastoid cell lines. Cyclomunine has little effect on small lymphocytes but acts rather on lymphoblasts. It has no effect on fibroblasts and myeloid cells. Cyclomunine partially inhibits the generation of suppressor cells induced by Con A and the generation of cytotoxic T cells in a mixed lymphocyte culture and totally inhibits the in vitro synthesis of Ig by PBL. Cyclomunine merits consideration as a new in vitro anti-lymphoblastic agent.

Cell Membrane↗
PubMed1979

[Description of an unusual enzymic activity cleaving the third component of complement].

A large enzymatic complex cleaving C3 (C3'ase) in the absence of magnesium (EDTA) has been partially characterized in two patients. On gel filtration EDTA-C3'ase was found in an 800 000 fraction containing antigenic C4, IgA and IgG in addition to alpha-2-macroglobulin and IgM normally present. EDTA-C3'ase was specifically neutralized by antibodies to IgG, IgA and C4. The characteristics of this unusual enzymatic complex are compatible with that of a C4b2a complex stabilized by its specific binding to an auto-antibody of the IgG and/or IgA class.

Chromatography, Gel↗
PubMed1979

Recurrence of dense deposits in transplanted kidneys: I. Sequential survey of the lesions.

Serial specimens from transplanted kidneys were obtained in 11 patients with dense deposit disease (DDD). The recurrence of DDD was obvious in 9 patients and appeared very early after grafting. Three different types of evolution of the lesions were observed. In 4 patients no modification of the lesions occurred with time, and in 2 of them the dense alteration alone persisted without any other glomerular changes. In 3 patients a progression of the lesions was observed, whereas a regression occurred in 1 other patient. From these observations the following sequence of the morphologic changes can be proposed: the dense alteration appears first and constitutes the specific marker of that disease; the C3 deposition in the kidney occurs later following the appearance of the dense lesion.

Basement Membrane↗
PubMed1979

Recurrence of dense deposits in transplanted kidney: II. Serum complement and nephritic factor profiles.

Dense deposit disease of the kidney is a rare form of chronic glomerulonephritis frequently associated with serum complement abnormalities (low C3 levels) and a circulating C3 convertase activator of the alternative pathway, the C3 nephritic factor (NF). Eleven patients with end-stage dense deposit disease underwent kidney transplantation. Of the 11, 7 had pretransplant low C3 and NF. In the posttransplant period, persisting low C3 levels were associated with persisting NF, although not quantitatively so. The original glomerular lesion recurred in the graft within 6 months in 9 of 11. Of these 9, 2 had no complement abnormalities either prior to or after transplantation. Pretransplant complement abnormalities were rapidly corrected in 4 of 7 patients whether or not recurrence of the original lesion occurred. Thus, serum complement profiles before and after transplantation are neither predictive nor indicative of recurrence.

Complement C3↗