Prolongation of canine cardiac allograft survival using donor-specific buffy coat pretransfusions.
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Biomedical subjects
Publications and source records attributed to H Lau.
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Ultraviolet irradiation of rat dendritic cells completely abrogated their allostimulatory capacity in a mixed lymphocyte reaction. Rat islets of Langerhans similarly irradiated remained hormonally functional when transplanted into syngeneic diabetic rats. Allogeneic transplantation across a major histocompatibility barrier of islets initially treated in vitro with ultraviolet irradiation resulted in prolonged allograft survival without the use of any immunosuppressive agents.
The effect of ultraviolet (UV) irradiation on the immunogenicity of rat pancreatic islets was examined in allograft and xenograft models. Direct UV irradiation (900 J/m2) of Lewis islets, isolated and hand-picked, does not alter pancreatic islet endocrine function in isograft experiments and results in indefinite islet allograft survival in streptozocin diabetic ACI rats without chronic immunosuppression. Direct UV irradiation, at an appropriate dose, also leads to indefinite islet xenograft survival of Lewis islets in B10-BR diabetic mice and prolonged survival of rat islets in Balb/C mice. When direct UV irradiation of islet allografts did not result in indefinite islet allograft prolongation [Wistar/Furth (W/F) to diabetic Lewis], the addition of brief peritransplant immunosuppression with cyclosporine (days 0, +1, and +2) resulted in permanent acceptance of islet allografts, a result not achieved by cyclosporine alone. The effectiveness of UV irradiation in abrogating islet allograft rejection in several experimental models is supported by in vitro studies showing that UV irradiation of stimulator cells, peripheral blood lymphocytes, splenocytes, and isolated rat dendritic cells abolishes any significant stimulation by such cells of totally histoincompatible thoracic duct responder lymphocytes. In vitro nonreactivity of mixed lymphocyte culture (MLC) with UV-irradiated stimulator cells and in vivo permanent allograft acceptance are reversed by the addition of a small number of untreated donor-type dendritic cells to either the MLC or the recipient bearing the permanent graft. The authors suggest that the primary effect of UV irradiation on immune alteration of islet allografts and xenografts is due to induction of a major metabolic change in the dendritic cells in the graft. This then leads to defective antigen presentation and results in either permanent or prolonged allograft and xenograft acceptance, depending on the degree of MLC stimulation between the islet donor and the diabetic recipient.
We have previously shown that direct ultraviolet (UV) irradiation of islets can reduce their immunogenicity without alteration of their endocrine function and effect prolonged survival of islet allografts in the Lewis-to-ACI strain combination without the use of immunosuppression. This study extends that work to investigate the survival of UV-irradiated Wistar-Furth islets in streptozotocin-diabetic Lewis rats, in which case the recipient is a relatively "high responder" to W/F alloantigens. Lewis recipients of 24-hr cultured W/F islets uniformly rejected islet allografts within one week of transplantation while the additional immunosuppression with cyclosporine (CsA) at 15 or 30 mg/kg on days 0, +1, and +2 was ineffective in prolonging islet allograft survival. Wistar-Furth islets, which were UV-irradiated at 850-900 J/m2 and cultured for 24 hr prior to transplantation, did not survive any longer than those in control animals receiving untreated islets (MST 5.5 +/- 1 day). When UV irradiation of islets was combined with recipient peritransplant treatment with CsA at 15 mg/kg on days 0, +1, and +2 islet allograft survival was markedly prolonged (MST of 18 +/- 4.1 days). Treatment of diabetic recipients of UV irradiated islets with an increased dose of CsA (30 mg/kg) during the same peri-transplant period (0, +1, +2 days) resulted in 100% islet allograft survival beyond 120 days. This data demonstrate the effectiveness and synergism between the use of the pretransplant UV irradiation of islet allograft and the peritransplant immunosuppression of the recipient with CsA in inducing prolonged islet allograft survival in "high responder" recipients, in which the singular use of either modality may be ineffective.
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Survival of allografts of islets of Langerhans in nonimmunosuppressed adult rats was prolonged by transfusions of donor blood irradiated with ultraviolet light before transplantation across a major histocompatibility barrier. This treatment is donor blood-specific and has produced greater than 160-day survival of transplanted islets without the administration of immunosuppressive agents.
Over a 2-year period the authors inserted 22 systemic to pulmonary artery shunts using a polytetrafluoroethylene (PTFE) graft in 19 children. A modified Blalock-Taussig shunt was established in 18 instances and an aorta to pulmonary artery shunt in 3: one patient had an aorta to right ventricle infundibulum shunt. Three children had obstructed grafts and in two others the grafts became stenosed; on of the latter group had successful removal of thrombus. The remaining grafts functioned well. Three other patients are presented. In two an interrupted aortic arch was repaired using a PTFE graft; one of these patients died at later closure of an aortopulmonary window, the other did well following repair of a ventricular septal defect and aortic valvotomy. The third child had a right ventricle to pulmonary artery shunt established for tetralogy of Fallot with pulmonary atresia; this resulted in some growth of the pulmonary arteries. The modified Blalock-Taussig shunt, using a PTFE graft, can be inserted without opening the pericardium, normal flow through the subclavian artery is not interrupted, the PTFE is easy to handle and the shunt can be inserted and taken down more easily than traditional shunts. For these reasons, the authors believe that this procedure, using PTFE, has an important role to play in the surgical management of children with congenital heart disease.
Torsion of the testicle in the neonate is uncommon. Only nine cases were seen in a 10-year period at the Izaak Walton Killam Hospital for Sick Children in Halifax, Nova Scotia. The authors describe briefly five of their cases to exemplify the features of and problems associated with this condition. They emphasize that (a) a reddish blue, nontender, scrotal or hemiscrotal swelling in the neonate should be considered as torsion of the testicle until proven otherwise and (b) torsion of the testicle in the neonate is a surgical emergency. If testicular tissue is to be saved urgent scrotal exploration is mandatory. The torsion may occur in utero (as is the usual case), at time of birth or post partum, but the time of occurrence cannot be judged. Finally, the authors discuss some of the controversies in the surgical management of this entity, including the surgical approach and management of the contralateral hemiscrotum.
Administration of high doses of triiodothyronine (T3) for 4 days to lactating rats evokes an increase in T3 levels in their sera and milk, as well as in the sera of pups suckled by them. Thyroid-stimulating hormone levels in sera of mothers and sucklings are decreased. Suckling rats of T3-treated mothers exhibit a precocious increase in the activity of jejunal sucrase and maltase as well as in activity of several liver acid beta-glycosidases.
Acid lipase activity in the livers of thyroidectomized rats is increased by administration of L-thyroxine. The response is dose-dependent and can be demonstrated within 12 h after treatment. L-Triiodothyronine also evokes a rapid increase in acid lipase activity, and this increase can be inhibited by coadministration of actinomycin D.
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Daily application of cortisone acetate (10mg/100g body wt.) or L-tri-iodothyronine (20 microng/100g body wt.) to female rats in the last (third) week of pregnancy elicits a precocious appearance of jejunal sucrase in their foetuses.
Activities of maltase, sucrase, lactase and acid-beta-galactosidase were studied in jejunum and ileum of term rat fetuses obtained by cesarian section. Female rats were either untreated or injected daily in the last (3rd) week of pregnancy with cortisone acetate (10 or 50 mg/100 g body weight) or L-triiodothyronine (20 or 50 microgram/100 g body weight). Two other control groups were injected with appropriate solvents. Cortisone or T3 treatment to mothers increased sucrase and maltase activity in jejunum and ileum of the offspring. Generally, higher doses of hormone were more effective. Lactase activity was increased by 25% in the jejunum by the higher dose of cortisone. Both doses of cortisone increased ileal lactase. Jejunal acid-beta-galactosidase activity was decreased in fetuses of T3-treated mothers.