No abstract

Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.

No abstract

The effect of long‐term denervation on neuromuscular recovery was studied in a rat hind limb model. The posterior tibial nerve was transected and repaired immediately or after denervation periods of 2 weeks, or 1, 3, 6, 9, or 12 months. Six months following reconstruction excellent axonal regeneration was seen across all nerve repairs irrespective of periods of denervation. However, there was a precipitous and profound decrease in the recovery of both muscle mass and integrated motor function if the reconstruction was delayed for longer than 1 month. Rather than a progressive change proportional to the length of the denervation period, significant, more discrete changes occurred sometime after 1 month of denervation that precluded a full recovery of muscle mass. Integrated motor function quantified using walking track analysis was impaired even after immediate nerve repair. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 858–866, 1997