FK 506-binding proteins (FKBPs) are a family of cytosolic proteins identified by virtue of their ability to bind the immunosuppressants FK 506 and rapamycin. While their function has been extensively studied in the immune system, little is known about their role during early embryonic development. Here we describe the cloning and expression of a new Xenopus FKBP (xFKBP). xFKBP encodes a 63-kDa ...

Calcineurin is a calcium/calmodulin-dependent phosphatase whose activity is required for the induction of T cell lymphokine production and proliferation. Although its specific role in T cell development is less well defined, studies with the immunosuppressive drugs cyclosporin A and FK-506 suggest that it is involved in both positive and negative selection of immature thymocytes. To more comple...

CYCLOSPORINE (Cy A)-induced pseudo-graft-versus-host disease (GVHD) developing in syngeneic rat bone marrow chimeras has features resembling classical acute and later chronic GVHD in the fully allogeneic bone marrow chimera. 1 These features develop in the early post-CyA period, and usually result in a mild, acute form of GVHD, followed by a more chronic autoimmunelike syndrome in a high percen...

I N AN earlier study, intravenous (IV) FK 506 appeared to be less well tolerated than the oral drug for two reasons. 1 One was the selection of a starting IV dose that was too high. The other may have been the use of pulse infusion therapy (over 2 to 4 hours) with consequent high peak plasma concentrations. In patients with unsatisfactory liver graft function, these peak values were sustained f...

FK 506 was given for immunosuppression in 14 liver recipients. The drug was used in the first 10 cases because the recipients under conventional immunosuppression had rejection, nephrotoxicity, or both. This salvage therapy was successful in 7 of the 10 attempts. 2 of the 10 patients in the original salvage group as well as 4 new patients underwent fresh orthotopic liver transplantation under F...

W E recently reported that intestinal transplantation from Lewis (LEW) to Brown Norway (BN) was intractable to FK 506 therapy because of a high incidence of a graft-versus-host disease (GVHD) syndrome) similar to that in the parent to F) hybrid offspring experiments of Monchik and Russell.2 However, transplantation in the opposite direction (BN to LEW) was highly successful without either GVHD ...

FK 506 (Tacrolimus-Prograf) was first used clinically in February 1989.1 and approved by the United States Food and Drug Administration in April 1994 as a new immunosuppressive agent for use after liver transplantation.2-4 It has also been utilized as the primary immunosuppressive agent after heart.5 lung,6 intestinal7 and islet8 transplantation. In renal transplantation, it has been studied ex...

Direct manipulations of neuronal activity have been shown to induce changes in DNA methylation (DNAm), although little is known about the cellular signaling pathways involved. Using reduced representation bisulfite sequencing, we identify DNAm changes associated with moderate chronic depolarization in dissociated rat hippocampal cultures. Consistent with previous findings, these changes occurre...

1. Cyclosporin A (CsA) is a widely used compound because of its potent immunosupressive properties, derived mainly from the inhibition of calcineurin, and also because of its ability to block the mitochondrial permeability transition pore (PTP). This second effect has been involved in the protection against apoptosis mediated by release of mitochondrial factors. We show here that CsA (1-10 micr...

In vitro interaction between tacrolimus (FK506) and four azoles (fluconazole, ketoconazole, itraconazole and voriconazole) against thirty clinical isolates of both fluconazole susceptible and -resistant Candida glabrata were evaluated by the checkerboard microdilution method. Synergistic, indifferent or antagonism interactions were found for combinations of the antifungal agents and FK506. A la...