IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs

Survivin is a member of the inhibitor of apoptosis protein (IAP) family. We investigated the antiapoptotic mechanism of Survivin, as well as its expression in 60 human tumor cell lines used for the National Cancer Institute's anticancer drug screening program. In cotransfection experiments, cell death induced by Bax or Fas (CD 95) was partially inhibited (mean +/- SD, 65% +/- 8%) by Survivin, whereas XIAP, another IAP family member, almost completely blocked cell death (93% +/- 4%) under the same conditions. Survivin and XIAP also protected 293 cells from apoptosis induced by overexpression of procaspase-3 and -7 and inhibited the processing of these zymogens into active caspases. In vitro binding experiments indicated that, like other IAP-family proteins, Survivin binds specifically to the terminal effector cell death proteases, caspase-3 and -7, but not to the proximal initiator protease caspase-8. Using a cell-free system in which cytosolic extracts were derived from control- or Survivin-transfected cells and where caspases were activated either by addition of cytochrome c and dATP or by adding recombinant active caspase-8, Survivin was able to substantially reduce caspase activity, as measured by cleavage of a tetrapeptide substrate, AspGluValAsp-aminofluorocoumarin. Similar results were obtained in intact cells when Survivin was overexpressed by gene transfection and caspase activation was induced by the anticancer drug etoposide. Survivin was expressed in all 60 cancer cell lines analyzed, with highest levels in breast and lung cancers and lowest levels in renal cancers. These findings indicate that Survivin, which is commonly expressed in human tumor cell lines, can bind the effector cell death proteases caspase-3 and -7 in vitro and inhibits caspase activity and cell death in cells exposed to diverse apoptotic stimuli. Although quantitative differences may exist, these observations suggest commonality in the mechanisms used by IAP-family proteins to suppress apoptosis.     

Evidence for defective skeletal mineralization in low-birthweight infants: the absorption of calcium and fat

Using serial metabolic balance techniques, the absorption and retention of calcium and the absorption of fat have beem measured over the first 30 to 70 days of life in 11 preterm and 2 full-term light-for-dates infants. They were fed either full-cream cow's milk, half-skimmed cow's milk, the proprietary filled milk S.M.A., or breast milk. The values for calcium intake, absorption and retention were compared with the rate of accumulation of calcium by the fetus in utero, which was calculated from published data on the chemical composition of fetal bodies. Infants fed breast milk had an absolute dietary deficiency of calcium. Those fed other milks ingested sufficient but they did not absorb enough. Though calcium absorption increased with increasing postnatal age, intrauterine rates of calcium retention were never achieved on any of the milks. The average retention of calcium by preterm infants as a percentage of intrauterine accumulation was, for cow's milk 38%, for S.M.A. 27%, and for breast milk 17%. The full-term light-for- dates infants absorbed and retained more calcium than the preterm infants; it was on average 52% of the amount accumulated by the human fetus for an equivalent weight gain. The average absorption of fat by preterm infants was, from the cow's milk preparations 55%, from S.M.A. 61%, and from breast milk 84%. The light-for-dates infants absorbed on average 87% of the breast milk fat. There was no evidence that the amount of calcium absorbed was materially influenced by fat malabsorption. The principal determinants of the amount of calcium absorbed were the length of gestation and postnatal age of the infant.     

A diagnostic formula for alcoholism

Clinical pathologies with unusually high morbidities in alcoholic populations were analyzed to determine their capacity to diagnose alcoholism. On the basis of five systemic variables it was possible to diagnose correctly nearly 75% of alcoholic and matched control subjects.     

Oxidation of (n)-InP by nitric acid

Au-oxide-semiconductor barriers have been studied in n-type InP. A comparison was made, using the ESCA technique and current/voltage characteristics, between different natural oxides obtained with nitric acid as reagent. With regard to the ideality factor, barrier height and oxide resistivity, the best oxide is obtained with acid in a gaseous phase, and the XPS spectra give an interpretation of the oxide composition.     

The place of informed consent in ethical dilemmas

Considers ethical questions raised by the psychotherapeutic treatment of a highly religious person to be specific instances of general issues in the conduct of psychotherapy. It is stressed that the therapist has a responsibility to insure that the consent of the client is obtained under conditions of full information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)