Participation of Survivin in mitotic and apoptotic activities of normal and tumor-derived cells.

Survivin is a member of the inhibitor of apoptosis (IAP) gene family, containing a single baculovirus IAP repeat (BIR) and no RING finger, that is expressed in many human cancers. Although it has been proposed to be involved in mitotic and cytokinetic processes, its functional subcellular distribution in the cytoplasm and nucleus, and its binding to centrosomes, spindle fibers, and centromeres in relation to these processes, is not fully resolved. We have analyzed the localization of Survivin in normal (Detroit 551, IMR-90) and tumor-derived (HeLa, Saos-2) cell lines, and found that it does colocalize with centrosomes in the cytoplasm during interphase, then moves to centromeres during mitosis, and finally localizes to the midbody spindle fibers during telophase. However, Taxol, a popular microtubule stabilizing agent that is frequently used in the study of these processes, severely disrupted the localization of Survivin. Taxol treatment of cells promoted extensive relocalization of Survivin with alpha-tubulin on microtubules during either interphase or mitosis. Survivin antisense oligonucleotide markedly sensitized HeLa cells to cell death induced by agents acting at the level of cell surface receptor (Fas pathway) or at the level of mitochondria (etoposide). HeLa cell death induced by Survivin antisense oligonucleotide could be partially complemented by Deterin, the Drosophila homolog of Survivin (Jones et al. [2000] J. Biol. Chem. 275:22157-22166). Reciprocally, a chimera of the Deterin BIR domain and Survivin C-terminus could rescue Drosophila Kc cells from death induced by transfection of a human caspase-7-expressing plasmid. These results indicate common components of Survivin and Deterin antiapoptotic action in the vertebrate and invertebrate phyla.

Psychotropic drug use by women: demographic, lifestyle, and personality correlates.

From initial telephone interviews with a random population of 1187 francophone women, 179 women participated in a further three-hour person-to-person interview focusing on the use of psychotropic medications. Psychotrope users typically were older, in poorer health, and had a lower level of education than abstainers. They showed an increased prevalence of nervousness, anxiety, depression, and restlessness. Initial contact with psychotrope use was through their general practitioners after presentation of vague and ill-defined symptoms. Psychotropic drug use was found among housewives, especially those with children, and among those unemployed but desiring work. Personality profiles of psychotrope users showed that they think of themselves as failures and are more distressed, with significantly greater life changes. Users scored higher on "femininity" subscales, apparently reflecting dependent and nondefensive personality types. In addition, personality measures defined psychotrope users as precise, methodical, cautious, serious, unassertive, and modest. The incompleteness of present unidirectional models of psychotropic drug use are discussed. Suggestions for future research include encompassing the cognitive organization of the psychotrope user within the context of social, affective, and physician influences on this form of coping style.

Psychotropic drug usage in Quebec urban women: pharmacological aspects.

Data on patterns of psychotropic drug use from a two-part study of Québec urban women are reported. Part I involved telephone interviews with 1187 women on their use of pain, sleep, and psychotropic medications. In Part II, 179 women participated in a further person-to-person interview. Areas covered included frequency and duration of use, efficacy of the product, dosage, presence of undesirable side effects, source of drug information, and the concomitant use of other medications. Diazepam and flurazepam (Valium and Dalmane) were the most frequently consumed psychotropes, with diazepam second only to aspirin as the most commonly used of all the medications. The majority of psychotropic users obtained the drug initially through a general practitioner for nonspecific health reasons, were satisfied with the efficacy of the drug, took the medication as directed, felt informed of the effects, and found no undesirable side effects. Multiple psychotrope use was not prevalent, and users of mood-modifiers were generally alcohol abstainers. The differences between the high and moderate users, including satisfaction with the psychotropes as well as initial dosages, are discussed along with comparative data from other similar drug studies. Findings lend credence to the hypothesis that the vague and ill-defined health problems precipitating a psychotropic prescription may in fact be economic, social, or psychological in origin.