Bcl-2 overexpression blocks activation of the death protease CPP32/Yama/apopain

Females who are affected by fragile X syndrome (FXS) can have significant physical, neuropsychological and emotional involvement. This study was designed to explore the relationships between these three domains and to learn how the degree of involvement in each of these phenotypic areas relates to molecular parameters including CGG repeat length and activation ratio (the proportion of normal FMR1 alleles on the active X chromosome). Three groups of females were studied: 35 women who grew up in a fragile X family but do not carry an FMR1 mutation, 92 women with a premutation, and 29 women with a full mutation. Correlations between neurocognitive, physical and emotional traits were calculated for each of the three groups. Within the full mutation group significant correlations were seen between schizotypal traits and full scale IQ. The Lie scale was significantly correlated with the physical findings index. The activation ratio correlated significantly with the measure of executive function (r = .50, P = .01). There was a trend toward correlations of activation ratio with the physical index score, outer ear prominence and IQ. CGG repeat number significantly correlated only with the physical index (r = .44, P = .01). Thus, activation ratio may be the more pertinent molecular parameter in full mutation women in determining the degree of cognitive and physical phenotypic involvement.     

High-density hybridoma perfusion culture. Limitation vs inhibition

Because our earlier work indicated a strong correlation between specific antibody productivity and cell density in perfusion culture, we conducted experiments to determine the optimum means of increasing cell density while maintaining high antibody productivity. The rates of medium supply and waste removal were varied to determine whether cell density was limited or inhibited, and whether a diffusable substance could be responsible for the correlation between antibody productivity and cell density. Nutrient supply was found to be a stronger determinant of cell density than waste removal; however, the rate of waste removal had a greater effect on cell growth at lower cell densities. Even at noninhibitory levels of ammonia and lactate, cellular metabolism was regulated to minimize their concentrations at lowered rates of waste removal. Separate step changes in glucose and glutamine resulted in increased cell density and antibody concentration. Specific antibody productivity increased following the step in glutamine, but not glucose. Both steps caused changes in cellular metabolism that prevented the levels of lactate and ammonia from reaching toxic levels.     

Protection by cyclosporine A against normothermic liver ischemia-reperfusion in pigs

BACKGROUND: Cyclosporine A (CYA) is primarily utilized as an immunosuppressant, but its mechanisms of action (including decreased neutrophilic free radical production and stabilization of mitochondrial and lysosomal membranes) may have beneficial effects in ischemia and reperfusion (IR) injury. This study was undertaken to examine the effect of CYA pretreatment on porcine liver histopathologic changes and enzymatic release caused by ischemia and reperfusion. MATERIALS AND METHODS: CYA was administered orally for 4 days prior to surgery in two doses (10 or 20 mg/kg) while controls received only the control vehicle. Pigs were then exposed to 4 h of hepatic ischemia followed by 2 h of reperfusion. RESULTS: Significant decreases in AST levels compared to controls were seen in high dose CYA pigs at the end of ischemia and at 30-min intervals during the reperfusion period. Controls exhibited necrotic hepatocytes and severe inflammatory cell infiltration, while high dose CYA animals demonstrated mild inflammatory cell infiltrates. Controls had decreased survival--20% did not survive reperfusion. CONCLUSIONS: This study indicates that CYA may be useful in decreasing initial damage resulting from warm hepatic IR injury.