DuBell, W. H., S. T. Gaa, W. J. Lederer, and T. B. Rogers. Independent inhibition of calcineurin and K1 currents by the immunosuppressant FK-506 in rat ventricle. Am. J. Physiol. 275 (Heart Circ. Physiol. 44): H2041–H2052, 1998.—FK-506 increases the cytosolic Ca21 concentration transient in rat ventricular myocytes by prolonging the action potential through inhibition of the K1 currents Ito and...

The interaction of FK-506 with K(V)1.3, stably expressed in Chinese hamster ovary cells, was investigated with the whole cell patch-clamp technique. FK-506 inhibited K(V)1.3 in a reversible, concentration-dependent manner with an IC(50) of 5.6 microM. Rapamycin, another immunosuppressant, produced effects that were similar to those of FK-506 (IC(50) = 6.7 microM). Other calcineurin inhibitors (...

Between January 1, 1989, and December 31, 1994, we have treated 122 primary heart recipients with FK 506 (group I) and 121 with cyclosporine (group II). Fifty patients in the cyclosporine (CyA) group received no lympholytic induction (CyA alone) and 71 others received lympholytic induction with either rabbit antithymocyte globulin or OKT3 (CyA+LI). The mean follow-up was longer in the FK 506 gr...

Evidence could not be found of immune modulation of liver regeneration. The powerful immunosuppressive drug FK 506, which augments the response after partial hepatectomy in normal rats, had the same effect in T cell-deficient nude rats. The cytotoxicity of natural killer cells in treated nude rats was not significantly changed by FK 506 therapy. However, the serum of FK 506-treated nude rats in...

Protocol: To detect the 506 polymorphism, a 567 bp SMPD1 genomic fragment is amplified using sense (5'-AGTAGTCGACATGGGCAGGATGTGTGG-3') and antisense (5'-AGTAGTGTCGACTTGCCTGGTTGAACC AC AGC-3') primers. Dot-blot hybridization is performed using allele-specific oligonucleotides for 506-Arg (5'-ACTACTCCAGGAGCTCT-3') and for 506-Gly (5'-ACTACTCCGGGAGCTCT-3'), which are hybridized at 42°C and washed ...

Purpose: Osteoarthritis (OA) is a common clinical chronic degenerative and progressive joint disease. Biological factors mechanical abnormalities are main pathogenic factors. Disorders of structure tissue morphology caused by instability, etc. will eventually lead to degeneration or even loss articular cartilage function. Relevant studies have shown that the incidence OA gradually increasing, d...

FK 506, a powerful. new immunosuppressive agent, is currently undergoing clinical trials in transplant patients. Like cyclosporine (CyA). FK 506 suppresses interleukin-2 production and receptor expression on T cells. 1.2 Additionally, both FK 506 and CyA are highly lipophilic. 3 CyA is mainly transported by lipoproteins in plasma.4 The objective of the present study is to characterize the distr...

L IVER transplantation has been increasingly used to treat end-stage liver diseases since the introduction of Cy A in combination with other immunosuppressive agents. 1 Although Cy A has a powerful immunosuppressive effect on allograft rejection, many transplant recipients still experience rejection episodes that are often irreversible. The nephrotoxicity of Cy A in some recipients has necessit...

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the liver that is characterized by progressive cholestasis and the development of secondary biliary cirrhosis. There is no widely recognized therapy for this disease, although anti-inflammatory agents (steroids), immunosuppressive agents (methotrexate), anti-fibrotics (colchicine), and choleretic agents (ursodeoxycholic a...

FK-506 increases the cytosolic Ca2+ concentration transient in rat ventricular myocytes by prolonging the action potential through inhibition of the K+ currents I to and I K[ J. Physiol. (Lond.) 501: 509-516, 1997]. Physiological and biochemical techniques were used in parallel to examine the electrophysiological mechanisms and the role of calcineurin inhibition in these effects. FK-506 prolong...