Gordon H. Davies

Effects of phenytoin on man's immunity: Evaluation of changes in serum immunoglobulins, complement, and antinuclear antibody

To determine the effects of phenytoin on serum immunoglobulins, complement, and antinuclear antibody conversion, a prospective, five-year longitudinal study was undertaken in 118 patients. Three major diagnostic groups were evaluated: 27 patients with idiopathic epilepsy, 50 with secondary epilepsy, and 41 with neuropathic syndromes without epilepsy. In addition, 83 normal volunteers were studied in a similar manner. Evaluations were performed prior to administration of phenytoin and at six-month intervals thereafter. Prior to treatment, patients with idiopathic epilepsy had a higher than expected incidence (13.5 percent, p less than 0.01) of low serum IgA (less than 61 mg/dl). Patients with secondary epilepsy and neuropathic disorders without epilepsy had a greater than expected incidence (9.2 percent, p less than 0.01; and 12 percent, p less than 0.01, respectively) of high serum IgA (greater than 417 mg/dl). Phenytoin treatment was associated with further decreases in serum IgA in patients with idiopathic epilepsy (p = 0.063) and secondary epilepsy (p = 0.008). Total serum IgE concentrations also decreased significantly in all patient categories during treatment with phenytoin. Minor decreases in serum IgG and IgM were noted, but serum IgD and complement remained unaffected. Antinuclear antibodies were observed with essentially the same frequency (10 percent) before and after phenytoin therapy.

The biosynthesis of mucopolysaccharides and collagen by the sex skin of estrogen-treated monkeys

Swelling of the sex-skin was induced in five immature female rhesus monkeys by the administration of estrogen. The mucopolysaccharide content of this skin was compared with that of unswollen chest skin from the same animals and with untreated controls. The major difference was a 5-fold increase in the hyaluronic acid content of the sex skin. The biosynthetic rates of hyaluronic acid, dermatan sulfate, collagen, and non-collagen protein were studied by measuring the rate of incorporation of radioactively labeled precursors into these substances either in vivo or in vitro. A differential effect of the hormone was seen in that much more [14C]glucose was incorporated into hyaluronic acid and dermatan sulfate by sex skin than by non-sex skin. The incorporation of [3H]proline into collagen was also greater in the sex skin than in the non-sex skin. The rate of transfer of label from extractable toinsoluble collagen was, however, unaffected. Relatively little differential effect was seen in the incorporation of [3H]proline into non-collagen protein.

Inhibition of hemagglutinin formation by thioguanine: dose-time relationships.

Summary Inhibition of hemagglutinin formation in mice was demonstrated with single doses of 2.5, 5, 10, 15 and 20 mg/kg of TG. If the drug was administered 18 or more hours after primary immunization, maximal block of antibody synthesis occurred. The minimal effective dose was 2.5 mg/kg injected 18 hours after antigenic stimulation. The same amount of drug given either before or after was ineffective. The timing was so specific that it permitted the design of a model system in which simultaneous inhibition of anti-human hemagglutinins was obtained without significant interference with the formation of anti-sheep hemagglutinins. The significance of the data are discussed. The technical assistance of Mr. John Niedra is gratefully acknowledged.

Effects of salicylate and phenobarbital on lymphocyte proliferation and function

Abstract Salicylate inhibited the response of human peripheral lymphocytes to phytohemagglutinim (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), and X-irradiated allogeneic lymphocytes. In addition, salicylate suppressed the generation of cytotoxic lymphocytes (CL) in vitro. The effect was dose dependent with over 90% inhibition at 48 mg%. Once CL were generated, however, the drug had little effect on their ability to lyse target cells. Sodium salicylate also suppressed the proliferative response of parental mouse thymocytes adoptively transferred into lethally irradiated F1 hybrid recipients as assessed by splenic uptake of [125I] iododeoxyuridine. High-dose, chronic treatment of both thymocyte donors and recipients was necessary to effect a 20–60% suppression. Similar chronic treatment of mice depressed the number of splenic plaque-forming cells by 48–72% when assayed 4 days after primary challenge with sheep erythrocytes. On the contrary, we could find no effect of phenobarbital on the response to PHA, mixed lymphocyte culture, or on the generation of CL.