Since the publication by Dreyfuss and associates 4 , 5 in which N-acetylprocainamide (NAP A) was found as a metabolite of procainamide (PA), a number of reports have appeared in the literature on the metabolism of procainamide. 6 , 12, 13, 17 These have also indicated the amount of NAPA in the plasma and urine of normal volunteers and patients. Graffner, Johnsson, and Sjogren 13 studied 4 normal volunteers and, after a single oral dose of PA -3H or after the administration of sustainedrelease preparations, recovered from 10% to 15% (12%) as NAPA in 24 hr. In another study, 339

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The transmembrane movement and distribution of cholesterol in the vesicular stomatitis virus membrane were studied by following the depletion of cholesterol from virions to interacting phospholipid vesicles and by exchange of radiolabeled cholesterol between virions and phospholipid-cholesterol vesicles. The kinetics of the cholesterol exchange or depletion reactions revealed the presence of two exponential rates: a rapid rate, dependent on the vesicle to virus ratio, and a slower rate, independent of the vesicle to virus ratio. The kinetics of cholesterol movement could be best interpreted by a model of the virion membrane considered as a two pool system in which approximately 30% of the cholesterol resides in the outer monolayer and approximately 70% in the inner monolayer. The half-time for equilibration of the two pools was calculated to be 4--6 h and was assumed to represent the time required for transmembrane movement of cholesterol across the bilayer. The initial rate of transfer of cholesterol from virus into vesicles increased when vesicle phospholipids contained more unsaturated and shorter chain fatty acids. Furthermore, the transfer of cholesterol appeared to occur by a collisional mechanism requiring membrane-membrane contact. Interaction with lipid vesicles did not significantly affect the integrity of the virion membrane as assessed by the relative inaccessibility of internal proteins to lactoperoxidase-catalyzed iodination and by the small loss of [3H]amino acid labeled protein from the virus.

Single lamellar phosphatidyl[methyl-2H]choline vesicles were incubated with an excess of unlabeled phosphatidylcholine vesicles or phosphatidylcholine-cholesterol vesicles containing 8 mol % glucuronosyldiglyceride. Incubation of the two vesicle populations was performed in the presence or absence of a purified phosphatidylcholine exchange protein. The negatively charged glycolipid donor vesicles could be completely removed by column chromatography on DEAE-Sephacel. Following incubation with exchange protein and subsequent fractionation, the -N(CD3)3 phosphatidylcholine acceptor vesicles exhibited a 61-73% enrichment of the unlabeled phosphatidylcholine in the outer monolayer. Upon incubation in an air atmosphere, no appreciable transbilayer movement of the outer monolayer -N(CH3)3 phosphatidylcholine was observed for at least 5 days. Between days 5 and 7, however, extensive transbilayer movement occurred, leading to an outer monolayer/inner monolayer phosphatidylcholine ratio of 2.1 on day 7. In phosphatidylcholine-6 mol % cholesterol vesicles treated similarly, the outside/inside ratio of the unlabeled phospholipid was 6.7, suggesting a much smaller percentage of transbilayer movement. The loss of transbilayer asymmetry which occurred during a 36-h period after day 5 could be estimated at the upper limit, t 1/2 approximately 7.3 h for phosphatidylcholine vesicles and t 1/2 approximately 53 h for phosphatidylcholine-cholesterol vesicles. The actual rates for transbilayer movement, however, were likely more rapid. Transbilayer movement occurred at a time period when oxidized phospholipid breakdown products had reached critical levels.

Summary The dose response curves of purified normal and chronic lymphocytic leukaemic lymphocytes to highly purified phytohaemagglutinin in 3‐ and 6‐day cultures have been defined. Normal lymphocytes cultured for 3 days were maximally stimulated by low concentrations of phytohaemagglutinin, in the range 0·4 to 1·4 μg phyto‐haemagglutinin/106 cells/ml. Higher concentrations of phytohaemagglutinin caused no further stimulation. Normal lymphocytes cultured for 6 days showed a progressively greater response to increasing concentrations of phytohaemagglutinin up to 15 μg phytohaemagglutinin/106 cells/ml. Chronic lymphocytic leukaemic lymphocytes responded subnormally to all ranges of phytohaemagglutinin concentrations tested, in both 3‐ and 6‐day cultures. The shape of the dose response curve resembled the normal curve in 2 of 5 cases of chronic lymphocytic leukaemic lymphocytes studied in 3‐day cultures, and in all 7 cases studied in 6‐day cultures. No evidence could be adduced of a consistently greater response of chronic lymphocytic leukaemic lymphocytes in 6‐day compared with 3‐day cultures. Five hours’ exposure of normal lymphocytes to an optimum phytohaemagglutinin dose did not result in maximum H3‐thymidine incorporation after 3 days in culture.