Paradoxical embolism of a shotgun pellet.

Paradoxical embolism of a projectile from the venous to arterial system is a rare occurrence, which can cause diagnostic confusion. We present a case of venous embolism of a shotgun pellet from the left upper extremity to the noncoronary sinus of the aortic valve across a secundum-type atrial septal defect. Prevention of distal embolism of the pellet was presumably a result of its containment by flow vortices created within the sinuses of Valsalva.

In vivo studies of the maintenance of peripheral transplant tolerance after cyclosporine. Radiosensitive antigen-specific suppressor cells mediate lasting graft protection against primed effector cells.

Cellular mechanisms responsible for maintenance of peripheral transplant tolerance in a rodent model were evaluated. Donor-specific tolerance was established in ACI rats given a vascularized heterotopic cardiac allograft followed by a 10-day course of cyclosporine. Tolerance was associated with a reduction in donor-specific cytotoxic T lymphocyte precursors and the presence within the spleen of cells capable of transferring suppression in adoptive transfer assays. Experiments using thymectomized animals revealed that the establishment and maintenance of tolerance occurred peripherally, independently of the thymus. Adoptive transfer experiments demonstrated that ongoing graft tolerance was mediated by suppressor cells that were antigen-restricted, radiosensitive, and capable of preventing allograft rejection by naive as well as sensitized cells in vivo. Studies designed to disrupt tolerance demonstrated a remarkable durability of graft protection once established, and give insight into the identity and mechanism of action of suppressor cells generated in this model.

Tissue-specific differences in the establishment of tolerance. Tolerogenic effects of lung allografts in rats.

With the increasing frequency of transplantation of two or more organs into a single recipient, it has become evident that different organs are rejected with different kinetics. In this study the kinetics of skin, lung, and heart allograft rejection were compared in a rodent model. To study the influence of different allografts on the recipient's immune system, simultaneous or sequential skin, lung, or heart transplants were performed in various combinations, using DA rats as recipients for PVG allografts. Recipients receiving primary allografts were treated postoperatively with ten doses of cyclosporine (CsA) or preoperatively with 4 doses of rabbit antirat thymocyte globulin (ATG). Subsequent transplants were performed a minimum of 40 days later without additional immunosuppression. All primary skin allografts and 60% of primary lung allografts were rejected, while 100% of the heart allografts were accepted indefinitely. Recipients of primary skin allografts rejected subsequent skin, lung, or heart allografts with accelerated kinetics. Recipients of primary heart allografts accepted subsequent skin, lung, and heart allografts indefinitely without further immunosuppression. Surprisingly, animals that had rejected a primary lung allograft accepted subsequent skin or heart allografts indefinitely. Simultaneously transplanted skin and lung allografts were concordantly rejected. However, these animals accepted a subsequent heart allograft indefinitely, suggesting a strong tolerizing effect of lung allografts. Our results indicate that tissue-specific differences are critical, not only in determining acceptance or rejection of a primary allograft but also in determining the fate of subsequent allografts.

Developments in cardiac transplantation.

Cardiac transplantation has matured as a therapeutic intervention, allowing definitive treatment of critically ill children and adults with end-stage heart disease. The ongoing critical shortage of donor organs continues to deny hundreds of individuals access to this intervention. Accordingly, many of the most meaningful recent advances made in the field of cardiac transplantation involve means of expanding our donor pool. While current immunosuppressive regimens have been considerably successful in the management of acute cellular rejection, management of the problems of acute and chronic vascular rejection remains disappointing. Advances in this arena remain particularly urgent for physicians and surgeons involved in the care of heart transplant recipients.

Immunologic and surgical developments in cardiac transplantation.

Clinical work in cardiac transplantation has focused on combating the major complications of this procedure, namely graft rejection and infection. Retrospective analyses suggest that prospective HLA typing, as is done in renal transplantation, may improve patient survival. Trials using FK 506 in cardiac transplantation have demonstrated some benefit using this agent over cyclosporine. Innovative immunologic interventions using novel monoclonal antibodies, methotrexate, total lymphoid irradiation, or photochemotherapy have shown promise in treating allograft rejection. Finally, prophylactic ganciclovir appears to prevent cytomegalovirus disease in seropositive transplant recipients; however, prevention of primary infection in seronegative patients may prove more difficult.

Expression of the alpha subunit of 7S nerve growth factor in the mouse submandibular gland.

alpha-NGF is an inactive serine protease that is associated in the mouse submandibular gland with a closely related serine protease, gamma-NGF, and the neurotrophic factor, beta-NGF. The heterogeneity of purified alpha-NGF has been examined by DEAE-cellulose chromatography and SDS polyacrylamide gel electrophoresis. A possible explanation for the observed heterogeneity is presented. Antibodies have been prepared against alpha-NGF and purified by affinity chromatography so that they do not cross-react with gamma-NGF. This antibody preparation recognizes two very similar proteins in male mouse submandibular gland RNA-directed cell-free translation mixtures. The expression of only one of these forms is regulated by testosterone. Oligonucleotide probes specific for each of the three NGF subunits have been prepared and used for Northern blot analysis of RNA from the mouse submandibular gland. The three subunits were found to be coordinately expressed and each were 30-fold more abundant in male than in female glands.