Cbl-b differentially regulates activation-induced apoptosis in T helper 1 and T helper 2 cells

We previously reported that ligation of CD3 induces antiapoptotic signals in T helper 2 (Th2) cells, and in contrast causes Th1 cells to undergo apoptosis. Here we show that Cbl-b is accountable for the unequal response, revealing a previously unknown cell-specific regulatory function for the molecule. Absence of Cbl-b resulted in resistance to activation-induced apoptosis in murine Th1 cells following CD3 ligation, akin to what is observed in Th2 cells containing Cbl-b. Concurrent with the apoptosis profile, CD3 ligation in the absence of Cbl-b induced raft mobilization and cytoskeletal rearrangement in Th1 cells. Despite their ability to signal from CD3, Th2 cells did not aggregate their rafts, providing an explanation for cell-specific activity of Cbl-b.     

Human rabies postexposure prophylaxis during a raccoon rabies epizootic in New York, 1993 and 1994.

We describe the epidemiology of human rabies postexposure prophylaxis (PEP) in four upstate New York counties during the 1st and 2nd year of a raccoon rabies epizootic. We obtained data from records of 1,173 persons whose rabies PEP was reported to local health departments in 1993 and 1994. Mean annual PEP incidence rates were highest in rural counties, in summer, and in patients 10 to 14 and 35 to 44 years of age. PEP given after bites was primarily associated with unvaccinated dogs and cats, but most (70%) was not attributable to bites. Although pet vaccination and stray animal control, which target direct exposure, remain the cornerstones of human rabies prevention, the risk for rabies by the nonbite route (e. g., raccoon saliva on pet dogs' and cats' fur) should also be considered.     

GAD65 and insulin B chain peptide (9-23) are not primary autoantigens in the type 1 diabetes syndrome of the BB rat

To investigate whether GAD65 whole molecule, GAD65 p35 or insulin B chain peptide (amino acids 9-23) play an essential role in the pathogenesis of type 1 diabetes in the BioBreeding (BB) rat, we gave serial injections of GAD65, p35 or insulin B chain (9-23) to six groups of BB/Worcester rats. The individual antigens were administered either intrathymically on day 2 and intraperitoneally in MF 59-0 adjuvant 5 times during the first 5 weeks, or by intranasal instillation once neonatally and 5 days/week for the following 6 weeks. Control groups were injected with vehicle only. Age of onset of diabetes and degree of insulitis were not different between controls and antigen-treated rats. Rats that received GAD65 intrathymically and intraperitoneally developed high GAD65-antibody titers without altering diabetes development. In GAD65-treated animals, serum antibodies recognized epitopes at 3 sites on GAD65 in diabetic animals but only at 1 site in non-diabetic animals. GAD65-injected animals also showed a significant reduction of IFN-gamma mRNA expression in the thymus. This study provides evidence against the hypothesis that GAD65 and insulin B chain peptide (9-23) are primary diabetogenic autoantigens in BB rats because immunizations with these antigens and GAD65-induced immune deviation did not alter the development of diabetes.     

Improved postoperative analgesia with preoperative piroxicam

Purpose

Piroxicam like other Non-Steroidal Anti-Inflammatory drugs can be used to provide postoperative analgesia. With a half-life of 50 hr given preoperatively its’ analgesic effect should continue postoperatively. This study compared the effects of 20 mg piroxicam given at different times in the perioperative period on postoperative analgesic requirement.

Method

Following ethical committee approval and written informed consent, 60 ASA I and II patients presenting for inpatient gynaecological laparoscopic surgery were given either 20 mg piroxicam or a placebo po two hours preoperatively, immediately before induction of anaesthesia or one hour postoperatively in a randomised double bind manner.

Results

Postoperative Visual Analogue Pain Scores were lower on admission to the recovery ward in patients given piroxicam preoperatively (Group 1), than in the other two treatment groups (groups 2 and 3). Pain scores were 2.72 vs 4.25 vs 6.67 respectively (P < 0.001). Pain scores did not differ at any other times. Time to first analgesic request was greater in the group 1 than in the other two treatment groups; 141 (61) min vs 115 (147) in Group 2 and 30 (36) min in Group 3. Nine patients in Group 1 requested further analgesia compared with 15 in Group 2 and 16 in Group 3. There were no piroxicam-induced side-effects.

Conclusion

Piroxicam given two hours preoperatively reduced pain scores, time to first analgesia and postoperative analgesic requirements compared with administration prior to induction or one hour postoperatively.