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Biomedical subjects

A G Sheil

Publications and source records attributed to A G Sheil.

At least 145 records · Page 8Linked to original sources
PubMed1987

Initial report of the Australian National Pilot Liver Transplantation Programme.

Our group began a National Pilot Liver Transplantation Programme in January, 1986, for which this report documents the results of the first 15 months' work. Seventy potential recipients (55 adults, 15 children) were referred for consideration for liver transplantation either directly or by state selection committees that had been established in most Australian states. The most common conditions for referral of adults were chronic active hepatitis, primary sclerosing cholangitis and primary biliary cirrhosis; 11 patients had fulminant hepatic failure. In children, the most common condition for referral was biliary atresia. Twenty-nine (41%) patients were considered unsuitable candidates for liver transplantation, 25 patients (21 adults and four children) were accepted for transplantation at a later time, and 16 patients (11 adults and five children) were selected for immediate transplantation. Of these 16 patients, three patients died before a donor could be found. Of the 13 patients to receive transplants (one patient received two transplants), 10 patients (seven of nine adults; three of four children) are alive and well; nine patients have good liver function and one patient has impaired liver function. The additional costs of the Programme to the hospitals were estimated at approximately $2 million a year. It is concluded that for those persons who require liver transplantation in Australia, worthwhile survival after this procedure can be obtained.

Adolescent↗
PubMed1987

Effects of therapy with azathioprine and prednisolone and ultraviolet irradiation on mouse skin immune function and immune cell markers.

The effects of ultraviolet irradiation (UVI) (290-400 nm) and/or systemic immunosuppressive drug therapy (azathioprine and prednisolone) on the immunocompetence of the skin of hairless (HRA/Skh-1) mice were investigated. Mice were studied for the density of ATPase+, Ia+ and Thyl X 2+ cells in the dorsal epidermis and contact hypersensitivity (CH) of skin to dinitrofluorobenzene (DNFB). Prednisolone therapy alone and UVI alone each reduced the densities of the three skin immune cell markers and CH responsiveness; azathioprine therapy alone had no such effects. When a suberythemal dose of UVI that induced a moderately depressive effect on these two skin parameters was used, additional azathioprine therapy produced no further depression; additional prednisolone therapy further depressed the densities of ATPase+ and Ia+ cells and CH responsiveness; additional therapy with combined azathioprine and prednisolone induced profound depression of the incidences of the three immune cell markers and of CH responsiveness. These data point to interaction between azathioprine/prednisolone therapy and UVI in depressing local immune function within skin which may contribute to the increased susceptibility of the sun-exposed skin of immunosuppressed kidney transplant recipients to infective and carcinogenic processes.

Adenosine Triphosphatases↗
PubMed1987

Effects of immunosuppressive therapy on the induction of skin tumors by ultraviolet irradiation in hairless mice.

The effects of therapy with four commonly used immunosuppressants--azathioprine, prednisolone, cyclophosphamide, and cyclosporine, on (UVI)-induced skin carcinogenesis were studied in the albino hairless (HRA/Skh-1) mouse. Following 30 weeks' exposure to UVI (290-400 nm) alone, 87% of mice developed skin tumors; the mean incidence of tumors at that time was 2.4 per mouse; and the tumors were predominantly papillomas (72%), with the remainder being carcinomas (25%) and keratoacanthomas (3%). Mice received immunosuppressive drug therapy beginning shortly after the start of UVI and continuing for up to 28 weeks. All drugs were given at immunosuppressive levels and dosages were comparable on a body weight basis to those used in clinical transplantation. Prednisolone had no effect on UVI-induced tumor development. Cyclosporine caused a moderate reduction in the latent period for tumor induction. Azathioprine and cyclophosphamide had strong promoting effects; the latent period for tumor induction was shortened and the tumor yield per mouse was increased (4.3 and 5.7 tumors per mouse, respectively, at 30 weeks after the start of UVI). Azathioprine, but not cyclophosphamide, also induced a larger proportion of carcinomas (43% and 15%, respectively). The results suggest that for kidney transplant recipients treated with the standard immunosuppressive drug regimen of azathioprine/prednisone, the increased susceptibility of the sun-exposed skin of these patients to squamous cell carcinoma is likely to be contributed to by specific promotion by the azathioprine therapy of the carcinogenic effects of sunlight.

Animals↗
PubMed1987

Scheduled and unscheduled DNA synthesis in epidermal cells of hairless mice treated with immunosuppressive drugs and UVB-UVA irradiation.

The effects of the immunosuppressive drugs azathioprine, prednisolone and cyclosporin A, and UV irradiation on scheduled DNA synthesis, representing mitotic activity, and unscheduled DNA synthesis, representing DNA repair activity, in the skin of hairless mice were determined autoradiographically following intradermal administration of [3H]-thymidine. Azathioprine and prednisolone, and, to a lesser extent, cyclosporin A, were found to impair normal repair of UVR-induced DNA lesions in epidermal keratinocytes. Prednisolone, but not the other two drugs, further suppressed the normal delayed mitotic response in the skin following UVR. The depressive effects of these drugs, particularly the combined azathioprine/prednisolone regime, on scheduled and unscheduled DNA synthesis are considered likely to predispose skin to mutagenic and carcinogenic processes.

Animals↗
PubMed1986

Diagnosis of renal allograft rejection by analysis of fine-needle aspiration biopsy specimens with immunostains and simple cytology.

Fine-needle aspiration biopsy specimens of renal transplants were analysed by means of commercially available monoclonal antibodies and an immunoperoxidase stain. Three cellular features associated with acute cellular rejection were identified--heavy infiltrates of activated T cells or large mononuclear cells strongly expressing HLA-DR antigens, and HLA-DR expression by renal tubular cells. A combination of semiquantitative scores for these features correctly identified rejection in 32 of 34 cases, with no false positives in cases of cyclosporin nephrotoxicity or stable graft function.

Antibodies, Monoclonal↗
PubMed1986

Immunopathology of renal allograft rejection analyzed with monoclonal antibodies to mononuclear cell markers.

The composition of the mononuclear cell infiltrate in rejecting renal allografts was determined on 96 renal biopsies and 22 nephrectomy specimens by the use of monoclonal antibodies to mononuclear cell surface markers and an indirect immunoperoxidase staining technique. During rejection the composition of the infiltrate was heterogeneous, with T cells (T11), monocytes (OKM1) and HLA-DR expressing mononuclear cells the most frequent sub-populations. B cells (B1) and activated T cells, identified by OKT10, were always in the minority. The T cells infiltrate usually included the helper/inducer (T4) and cytotoxic (T8) subclasses, which suggests that both may contribute to the mediation of rejection. Whether T4 or T8 predominated in the graft did not relate to the ratio of T4:T8 in blood, the HLA A, B or DR incompatibilities of the graft, or the immunosuppressive used. The frequency of T11, T4, T8, HLA-DR positive cells and monocytes, but not B cells, increased with the severity of rejection and was similar in biopsies from patients immunosuppressed with Cyclosporine (CSA) to those given a combination of azathioprine, prednisone and antilymphocyte globulin (AZA). Severe rejection episodes which did not respond to treatment with corticosteroids were more often characterized by a predominance of T8 over T4 cells and T cells infiltrating the glomeruli. In grafts with evidence of cellular rejection, renal tubular cells were shown to have a marked increase in their expression of HLA-DR antigens compared to normal kidneys or grafts with minimal rejection. The expression of HLA-DR antigens on graft tubular cells correlated with the presence of T cells in the interstitium and the severity of rejection, except for moderate rejection in CSA treated biopsies, in which HLA-DR expression was lower than in AZA biopsies. These immunopathological studies have demonstrated that a variety of potential effector cells exist within the graft, and several features have been identified which may assist in assessing the prognosis of the rejection episode.

Antibodies, Monoclonal↗
PubMed1986

Effects of ultraviolet radiation and immunosuppressive therapy on mouse epidermal cell kinetics.

The effects of immunosuppressive drugs on epidermal cell mitotic activity and the proliferative response of epidermis following ultraviolet radiation (UVR) were tested. Hairless (Skh-hr 1) mice were treated with immunosuppressive drugs at equivalent clinical doses with or without concomitant UVR (290-400 nm). Epidermal parameters measured were mitotic index (Im), rate of entry into mitosis (Fm), flash labelling index (FLI), rate of entry into DNA synthesis (Fs) and DNA content (flow cytometric analysis). In non-irradiated skin, prednisolone therapy depressed both mitotic activity and DNA synthesis; azathioprine and cyclosporin A had no effect; cyclophosphamide therapy increased the Fm and FLI values. Following repeated doses of UVR, there were enhanced mitotic activity and DNA synthesis in epidermis. Prednisolone therapy moderately depressed both proliferative responses; cyclophosphamide enhanced mitotic activity; azathioprine and cyclosporin A had no effect on these responses. The significance of these findings in relation to potential for increased susceptibility of skin to UV-induced carcinogenesis is discussed.

Animals↗