Biomedical subjects
J Koulack
Publications and source records attributed to J Koulack.
Importance of minor histocompatibility antigens in the development of allograft arteriosclerosis.
Although acute rejection has been mostly ameliorated with the use of powerful immunosuppressive drugs, kidney and heart transplants continue to succumb to a more chronic response characterized by intimal lesions in the graft vasculature. This late-stage response is referred to as allograft arteriosclerosis. Allorecognition is clearly involved in the initiation of this response but the relative importance of major histocompatibility (MHC) and minor histocompatibility (mH) antigens remains unclear. By taking advantage of the B10 congenic set of mice and our newly described mouse aortic interposition graft model we have been able to assess the contribution of these antigens to the development of the concentric intimal lesions characteristic of allograft arteriosclerosis. We performed transplants between syngeneic animals, animals which were disparate at both MHC and multiple mH, animals which were disparate at MHC only, and animals which were disparate at multiple mH antigens only. H-Y antigen variation was controlled for by performing all transplants between female mice. In all cases the recipients were C57BL/10 (H-2b) mice. Both cellular infiltration into the intima and resulting intimal thickness were measured at 2, 4, 8, and 13 weeks posttransplant. At all time points, the grafts from MHC disparate only donors showed less severe intimal lesions than the grafts from fully disparate or mH disparate donors. This difference reached statistical significance at 4 and 13 weeks. This suggests that mH antigens are as immunogenic as MHC antigens with respect to the generation of allograft arteriosclerosis. These findings are not unique to vascular grafts and may relate to the importance of indirect antigen presentation in the development of chronic rejection.
Development of a mouse aortic transplant model of chronic rejection.
Chronic rejection is the most common cause of late graft failure after solid organ transplantation. A model of chronic rejection, the rat aortic allograft, has histologic features that parallel those in the vessels of human transplanted organs. However, the molecular tools required to dissect the immunology of chronic rejection are unavailable in the rat. We developed aortic transplantation in the mouse as a new model of chronic rejection. This will allow the use of the diversity of recombinant cytokines and monoclonal antibodies available for the mouse and its well-defined genetics to investigate chronic rejection in greater detail. We describe the perioperative care and surgical technique for the model in which a 1 cm segment of donor thoracic aorta was used to replace a section of recipient abdominal aorta below the renal arteries and above the aortic bifurcation. Mortality rates were initially high (70%) due to thrombosis and shock. Changes in technique and operator facility resulted in a high rate of success (75%). After 192 operations, the current success rate is > 80%. Mice free from complications at 12 hrs postop had indefinite survival, and after 2 months the typical vascular lesion of chronic rejection was present. This new model of chronic rejection will be a valuable tool to study the molecular immunology and genetics of chronic rejection.
Routine inguinal hernia repair in the pediatric population: is office follow-up necessary?
Routine inguinal hernia repair in the pediatric population has a low complication rate. Very few complications are identified at follow-up, which brings into question the necessity of the traditional postoperative visit. A retrospective review of patients who had undergone a routine inguinal hernia repair in 1991 at our institution was done in order to determine our current follow-up practices and complication rate. To determine the perceived necessity for the follow-up visit, parents were given a short telephone questionnaire. Of 175 eligible patients, questionnaires were completed on 145. Of these 145 patients, 77 were seen in follow-up by the pediatric surgeon only, 43 by the family doctor only, 12 were seen by both, and 13 patients had no physician follow-up. The sole complication was a stitch abscess (complication rate 0.7%). Results of the questionnaire showed that 90% of parents felt the follow-up visit was "helpful," 80% felt it was "necessary," and 35% would have been satisfied with telephone follow-up. The main purpose of the postoperative visit appears to be parental reassurance. Careful preoperative and postoperative instruction and reassurance may be sufficient in a significant number of cases.