Increases in cytochrome P-450 in cultured hepatocytes mediated by 3- and 4-carbon alcohols

The amount of cytochrome P-450 was increased to different extents after treatment of cultured chick embryo hepatocytes with n-propanol, isopropanol, n-butanol, or isobutanol, These increases were associated with increases in benzphetamine demethylase activity, a cytochrome P-450-catalyzed oxidation, and glucuronidation of phenol red, catalyzed by UDP-glucuronyl transferase. The responses were similar to those obtained with ethanol or propylisopropylacetamide, which are phenobarbital-like inducers. Pretreatment of cells with cycloheximide prevented the increases in both cytochrome P-450 and glucuronidation of phenol red, indicating that protein synthesis was required for these responses.     

Low-dose steroid therapy in cyclosporine-treated renal transplant recipients with well-functioning grafts. The Canadian Multicentre Transplant Study Group.

OBJECTIVE: Low-dose prednisone given on alternate days as a steroid adjunct to cyclosporine therapy was investigated primarily for its influence on kidney graft and patient survival and, secondarily, on renal function and complications. DESIGN: Multicentre randomized double-blind clinical trial. SETTING: Fourteen Canadian transplant centres. PATIENTS: A total of 523 patients with well-functioning renal transplants (cadaveric grafts or grafts from living related donors) and without active graft rejection reactions who were entered into the trial from 1982 to 1985. INTERVENTION: Patients were randomly assigned 90 days after transplantation to receive either placebo (260 patients) or low-dose prednisone (263 patients). MAIN OUTCOME MEASURES: Graft and patient survival. MAIN RESULTS: After at least 5 years of follow-up 50 patients assigned placebo had lost their graft and 17 had died; the corresponding figures for those assigned prednisone were 38 and 16. After an average interval of 1.4 years 143 patients in the placebo group and 123 patients in the prednisone group had stopped therapy with the test drug or had had their treatment group decoded or both. Patients were withdrawn from the study 2 years after stopping the test therapy. The actuarial 5-year graft survival rates were 73% and 85% in the placebo and prednisone groups respectively (p = 0.03), and the actuarial 5-year patient survival rates were 92% and 94% respectively (p = 0.6). This analysis included 43 and 29 graft losses and 14 and 12 deaths in the placebo and prednisone groups respectively. Weibull parametric modelling of graft survival identified the following variables as risk factors for graft loss: histocompatibility leukocyte antigen B (HLA-B) mismatching (p = 0.007), donor death from cerebrovascular accident (p = 0.01), increased donor age (p = 0.02) and being a male recipient (p = 0.05). When these factors were included in the Cox proportional hazards model, the influence of assigned treatment on graft survival was reduced to p = 0.1. Donor death from cerebrovascular accident (p = 0.002), diabetes mellitus in the recipient (p = 0.02) and increased recipient age (p = 0.05) were risk factors for patient death. Renal function and incidence of complications were similar in the treatment groups. CONCLUSIONS: Continued administration of low-dose prednisone on alternate days is advisable, particularly in patients with cadaveric grafts and those with previously failed transplants.     

REGULATION OF THE IMMUNE RESPONSE : I. REDUCTION IN ABILITY OF SPECIFIC ANTIBODY TO INHIBIT LONG-LASTING IGG IMMUNOLOGICAL PRIMING AFTER REMOVAL OF THE FC FRAGMENT

The ability of 7S and F(ab')₂ antibody fragments to suppress priming with low doses of antigen was compared. The 7S preparation was approximately 100–1000 times more potent than the F(ab')₂ preparation when the agglutinin titers of the two preparations were the same. The presence of any ability to suppress priming in the F(ab')₂ preparation may reflect an inherent capacity of the F(ab')₂ antibody or contamination with small amounts of 7S antibody. The difference between 7S and F(ab')₂ antibody in ability to suppress priming is attributed to the lack of the Fc portion on the F(ab')₂ antibody. The Fc portion may be needed to prevent rapid excretion of antibody from the body, to induce rapid phagocytosis of antigen-antibody complexes with consequent breakdown and elimination of antigen, or to inactivate or suppress the antigen-sensitive cells from reacting to antigenic determinants. More detailed studies will permit a better assessment of the importance of these three possible regulatory roles of the Fc portion of the immunoglobulin in the immune response.