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Biomedical subjects

B M Hall

Publications and source records attributed to B M Hall.

At least 73 records · Page 4Linked to original sources
PubMed1988

Comparison of three immunosuppressive regimens in cadaver renal transplantation: long-term cyclosporine, short-term cyclosporine followed by azathioprine and prednisolone, and azathioprine and prednisolone without cyclosporine.

We conducted a randomized trial in seven Australian hospitals of the efficacy and safety of three immunosuppressive regimens after first transplantation of a cadaver kidney: long-term cyclosporine, short-term (three months) cyclosporine followed by azathioprine and prednisolone, and azathioprine and prednisolone without cyclosporine. Patients assigned to long-term cyclosporine (n = 138) or short-term cyclosporine followed by azathioprine and prednisolone (n = 141) had similar actuarial 12-month survival (98.4 vs. 96.4 percent) and graft survival (83.9 vs. 82.1 percent). Patients assigned to receive only azathioprine and prednisolone (n = 138), with optional use of antithymocyte globulin, had a significantly poorer survival rate (91.3 percent, P = 0.015) because of deaths from cardiac causes and infection, but their graft survival of 76.0 percent (P = 0.31) did not differ significantly from that of either group receiving cyclosporine. After the switch from cyclosporine to azathioprine and prednisolone, 15 percent of patients had reversible rejection episodes, but the frequency of rejection and graft loss did not differ from that in the long-term cyclosporine group. After the change to azathioprine and prednisolone, serum creatinine levels declined in nearly all patients, so that after three months they were comparable to those in the group receiving azathioprine and prednisolone only, and significantly lower than those in the group receiving long-term cyclosporine therapy (P less than 0.003). We conclude that the two cyclosporine regimens result in comparable patient and graft survival, but that changing to azathioprine and prednisolone at three months improves graft function.

Adult↗
PubMed1988

Effects of immunosuppressive drugs on functions of activated T lymphocytes. Cyclosporine inhibition of gamma interferon production in the presence of interleukin.

Expression of HLA DR by tubular cells of renal allografts of patients treated with cyclosporine (CsA) is less than that from patients treated with a combination of methylprednisolone (MPRED) and azathioprine (AZA). To examine the reason for this difference, the effects of immunosuppressive drugs on functions of alloactivated mononuclear cells, which had been primed in culture without added immunosuppressive drugs, was compared. CsA, 0.1 microgram/ml, inhibited gamma interferon production by 79 +/- 7% and in the presence of interleukin 2 (IL-2) by 82 +/- 10%. CsA, 0.1 microgram/ml, inhibited cytotoxic effector function by 11 +/- 12% and proliferation of cells that had been washed to remove lymphokines by 61 +/- 17% but only 17 +/- 8% in the presence of IL-2. MPRED, 20 micrograms/ml, inhibited gamma interferon production by washed alloactivated cells by 79 +/- 12% and 59 +/- 7% with IL-2. MPRED, 20 micrograms/ml, inhibited proliferation of washed cells by 36 +/- 4 and 86 +/- 3% with or without IL-2, respectively, and it inhibited cytotoxic effector function by 71 +/- 16%. AZA and its metabolites 6-mercaptopurine and 6-thioinosinic acid had little inhibitory effect on any tested function of activated lymphocytes at a concentration of 0.2 microgram/ml. These results indicate that CsA has a greater inhibitory effect on gamma interferon production by activated lymphocytes in the presence of IL-2 than MPRED or AZA in vitro, which may explain their differential effects on renal tubular cell HLA DR expression in vivo. Gamma interferon production was the only activated lymphocyte function tested that was inhibited by CsA in the presence of IL-2. MPRED was able to inhibit all functions, albeit to a lesser degree, in the presence of IL-2 or of IL-2-containing culture supernatants.

Azathioprine↗
PubMed1988

Expression of HLA antigens on renal tubular cells in culture. II. Effect of increased HLA antigen expression on tubular cell stimulation of lymphocyte activation and on their vulnerability to cell-mediated lysis.

Episodes of renal allograft rejection are characterized by an infiltrate of mononuclear leukocytes into the graft and increased HLA antigen expression by graft tubular cells. As HLA antigens are important immune-recognition molecules, we examined whether their increased expression during rejection might contribute to the rejection process. Interferon gamma (IFN-gamma)-treatment of cultured human kidney (HK) cells induced them to increase HLA antigen expression and caused a slight, but nonsignificant increase in their capacity to stimulate proliferation of allogeneic lymphocytes in primary mixed lymphocyte kidney culture (MLKC) (maximum of 8110 +/- 5015 vs. 3966 +/- 4050 counts/min on day 8), which was further increased by addition of IL-1. This proliferation never approached that induced by peripheral blood mononuclear stimulator cells (maximum of 40,325 +/- 10,694 counts/min on day 5), and addition of HK cells to mixed lymphocyte culture inhibited proliferation. There was no difference in lysis of IFN-gamma-treated or untreated HK-cell targets by "specific" cytotoxic effector cells produced in mixed lymphocyte culture using stimulator lymphocytes from the kidney cell donor (49.4 +/- 20% vs. 50.4 +/- 26% specific release in CML). Lysis by 3rd-party cytotoxic effectors produced in MLC using stimulator lymphocytes unrelated to the kidney-cell donor was greater for untreated HK cells (27.4 +/- 20%) than for IFN-gamma-treated HK targets (7.6 +/- 6%, P less than 0.001). IFN-gamma-activated naive mononuclear leukocytes lysed untreated HK targets but not IFN-gamma-pretreated targets, and this nonspecific cytotoxicity was mediated by lymphocyte- but not monocyte-enriched cell populations. HK cells are therefore poor stimulators of alloproliferation even when they express increased HLA antigen. They are lysed by both specific and nonspecific effector cells, and exposure to IFN-gamma makes them less vulnerable to nonspecific cytotoxicity and by inference, more vulnerable to specific cytotoxicity.

Antigens, Differentiation↗
PubMed1988

The regulation of autoantibody production in Heymann's nephritis by T lymphocyte subsets.

The role of T lymphocyte subsets in the regulation of the autoantibody response to renal tubular antigen and the development of Heymann's nephritis (HN) in different rat strains was investigated in the present study. WF rats were highly susceptible to HN induction, PVG rats were moderately susceptible, whereas DA and BN were resistant. The induction of an autoantibody response to renal tubular antigen and HN in PVG rats was T cell-dependent as they were abrogated by neonatal thymectomy and T cell depletion after adult thymectomy, whole body irradiation and bone marrow reconstitution. Reconstitution of neonatal thymectomized and adult thymectomized whole body irradiated and bone marrow reconstitution of PVG rats with different T lymphocyte subsets revealed that the induction of an autoantibody response to renal tubular antigen in these animals required help from a long lived, W3/25+ T cell subset and was down regulated by a MRC OX8+ T cell subset. Adoptive transfer experiments demonstrated that the suppressor T cells involved were short lived and were probably generated by the interaction between a W3/25+ inducer and a MRC OX8+ precursor subpopulation. The suppressor precursor T cells were recently derived from the thymus as the suppressor T cell response was abrogated by adult thymectomy, an effect which could only be fully restored by thymic grafting or injection of adult thymocytes but not by the injection of normal spleen or lymph node cells. As adult thymectomy had less effect on the autoantibody response and HN development in the highly susceptible WF rats, the difference in disease susceptibility between the WF and PVG rats may be the result of different suppressor T cell recruitment from the adult thymus. Since adult thymectomy did not affect disease development in the DA and BN rats, the recently thymus-derived suppressor T cells did not contribute to innate disease resistance in these rat strains.

Animals↗
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↗