The immunosuppressants cyclosporin A and FK506 (tacrolimus) can block the phosphatase calcineurin, thereby inhibiting gene transcription directed by the cyclic AMP (cAMP)- and calcium-responsive transcription factor, cAMP response element (CRE)-binding protein, and its binding site, CRE, in various cell lines. This action is a novel molecular mechanism of cyclosporin A and FK506 action. Because...

This report describes a patient who developed cyclosporin-induced thrombotic microangiopathy in a renal allograft. Cyclosporin-induced thrombotic microangiopathy is considered by many as a contraindication to subsequent therapy with cyclosporin. This case is notable for successful treatment with cyclosporin following resolution of thrombotic microangiopathy in a renal allograft.

1. The nephrotoxic effects of cyclosporin A may diminish the ability of the transplanted kidney to increase the glomerular filtration rate and effective renal plasma flow during infusion of dopamine or amino acids. 2. The present study included 16 renal transplant recipients transplanted for more than 6 months. Eight of the patients were on immunosuppressive treatment including cyclosporin A [c...

The ascomycete fungus Tolypocladium inflatum, a pathogen of beetle larvae, is best known as the producer of the immunosuppressant drug cyclosporin. The draft genome of T. inflatum strain NRRL 8044 (ATCC 34921), the isolate from which cyclosporin was first isolated, is presented along with comparative analyses of the biosynthesis of cyclosporin and other secondary metabolites in T. inflatum and ...

The modes of action of topical cyclosporin A were studied in rabbits. Immunorejection of corneal allografts was provoked by placing the grafts eccentrically, in contact with the limbus. Topical application of cyclosporin A five times daily for 28 days prevented the rejection of corneal allografts. All grafts were rejected in the control animals. The seven rabbits of the cyclosporin A group were...

We describe a simplified isocratic "high-performance" liquid-chromatographic method for measuring a new immunosuppressive drug, cyclosporin A, in biological fluids with use of its analogs cyclosporin C and cyclosporin D as internal standards. The method is reproducible and accurate and appears to be specific for cyclosporin A; the detection limit is 31 micrograms/L. The chromatographic measurem...

Daily treatment with cyclosporin at a dose of 25 mg/kg for 14 d gave complete suppression of the development of collagen arthritis and adjuvant arthritis in Sprague-Dawley rats during an observation period of 45 d. To study whether the immunologic unresponsiveness produced by cyclosporin is antigen specific, we rechallenged the cyclosporin-protected rats with either type II collagen or complete...

1. The effects of cyclosporin A on the increase in matrix PPi and consequent swelling of energized liver mitochondria incubated with 1 mM-butyrate, 30,uM-bongkrekic acid or 0.1-35,M-Ca2+ [Halestrap (1989) Biochim. Biophys. Acta 973, 355-382] were studied. 2. Cyclosporin (1 ZM) had no significant effect on the swelling induced by butyrate, bongkrekic acid or Ca2+ at concentrations of less than 0...

The characteristics of cyclosporin A transport have been studied in cultured kidney epithelial cell line LLC-PK1. The uptake of cyclosporin A by LLC-PK1 cells was time-dependent and reached a steady state at about 30 min. The initial uptake was saturable and was inhibited by cyclosporin A analogs, cyclosporin C and D and by verapamil, but not by metabolic inhibitors such as 2,4-dinitrophenol an...

This study tests the hypothesis that the clinical response to cyclosporin therapy of patients with chronic severe asthma is related to the sensitivity of their T-lymphocytes to the antiproliferative effects of cyclosporin in vitro. In a previous study, we observed such a relationship with glucocorticoids and the same lectin-driven proliferation assay was used in the present study. Peripheral bl...