Programmed cell death occurs spontaneously during spermatogenesis and can be induced in a cell- and stage-specific manner by mild testicular hyperthermia. Studies using transgenic mice suggest the involvement of Bcl-2 proteins in regulating germ cell apoptosis. To delineate further the pathways involved, we examined the temporal changes in proapoptotic Bax and antiapoptotic Bcl-2 in rat testes after transient exposure to heat (43 degrees C for 15 min). Germ cell apoptosis, involving exclusively early (I-IV) and late (XII-XIV) stages, was activated within 6 h. Initiation of apoptosis was preceded by a redistribution of Bax from a cytoplasmic to perinuclear localization within 0.5 h of heating as assessed by immunocytochemical methods. In contrast, Bcl-2 is distributed both in the cytoplasm and nucleus in those cell types susceptible to heat-induced apoptosis. Despite the striking redistribution, Bax levels remained unchanged as determined by Western analysis; Bcl-2 levels increased significantly by 6 h after heat exposure. Reverse transcription-polymerase chain reaction analysis indicated no change in either Bax or Bcl-2 mRNA levels in response to heat, suggesting the involvement of post-transcriptional rather than transcriptional mechanisms mediating their activity. The marked subcellular redistribution of Bax prior to activation of apoptosis and the increase in Bcl-2 suggest an involvement of Bcl-2 family members in heat-induced apoptotic death of germ cells.
Fletcher and Bloom (1988) have argued that as readers read narratives, clause by clause, they repeatedly focus their attention on the last preceding clause that contains antecedents but no consequences in the text. This strategy allows them to discover a causal path linking the text's opening to its final outcome while minimizing the number of times long-term memory must be searched for missing antecedents or consequences. In order to test this hypothesis, we examined the reading times of 25 subjects for each clause of eight simple narrative texts. The results show that: (1) causal links between clauses that co-occur in short-term memory (as predicted by the strategy) increase the time required to read the second clause; (2) potential causal links between clauses that never co-occur in short-term memory (again as predicted by the strategy) have no effect on reading time; and (3) reinstatement searches are initiated at the end of sentences that are causally unrelated to the contents of short-term memory or that contain clauses that satisfy goals no longer in short-term memory. These results support the claim that subjects engage in a form of causal reasoning when they read simple narrative texts.In the research reported here, we have examined the joint implications of two well-known claims about narrative comprehension. The first of these asserts that comprehension is a problem-solving process, in which the reader must discover a series of causal connections that link a text's opening to its final outcome (Black & Bower, 1980;Schank, 1975;Trabasso & Sperry, 1985;Trabasso & van den Broek, 1985). The second holds that a strategic process focuses a reader's attention on a subset of the information inhis or her short-term memory after each sentence is read, and that comprehension is facilitated if an appropriate connection exists between this information and the sentence that follows (Fletcher, 1981(Fletcher, , 1986Kintsch & van Dijk, 1978;Miller & Kintsch, 1980;van Dijk & Kintsch, 1983). Fletcher and Bloom (1988) have argued that both claims can be correct only if the attentionfocusing process identifies the most likely causal antecedent of the sentence that will follow and if the correct antecedent (or sometimes consequence) is reinstated from long-term memory whenever this process fails.To discover how such a process might work, Fletcher and Bloom (1988) examined a sample of narrative texts and found that the most likely causal antecedent of any This research was supported in part by the Center for Research in Learning, Perception, and Cognition at the University of Minnesota, and by Grants MH42468-DI and AFOSR-86-D280 to Charles R. Fletcher.Portions of the research were presented at the 1987 convention of the Psychonornic Society in Seattle, WA. We are grateful to Alice Healy, Ed O'Brien, Tom Trabasso, and an anonymous reviewer for their comments on an earlier version of this paper. Requests for reprints should be addressed to Charles R. Fletcher, Department of Psychology, University of Minnesota, 75 East River R...
Studies of visit-to-visit office blood pressure variability (OBPV) as a predictor of cardiovascular events and death in high-risk patients treated to lower BP targets are lacking. We conducted a post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), a well-characterized cohort of participants randomized to intensive (<120 mm Hg) or standard (<140 mm Hg) systolic BP targets. We defined OBPV as the coefficient of variation of the systolic BP, using measurements taken during the 3-,6-, 9- and 12-month study visits. In our cohort of 7879 participants, older age, female sex, black race, current smoking, chronic kidney disease and coronary disease were independent determinants of higher OBPV. Use of thiazide-type diuretics or dihydropyridine calcium channel blockers was associated with lower OBPV, while angiotensin converting enzyme inhibitors or angiotensin receptor blocker use was associated with higher OBPV. There was no difference in OBPV in participants randomized to standard or intensive treatment groups. We found that OBPV had no significant associations with the composite endpoint of fatal and non-fatal cardiovascular events (N=324 primary endpoints; adjusted hazard ratio [HR] 1.20, 95% confidence interval [CI] 0.85–1.69, highest versus lowest quintile), nor with heart failure or stroke. The highest quintile of OBPV (versus lowest) was associated with all-cause mortality (adjusted HR 1.92, CI 1.22–3.03), although the association of OBPV overall with all-cause mortality was marginal (p=0.07). Our results suggest that clinicians should continue to focus on office BP control rather than on OBPV unless definitive benefits of reducing OBPV are shown in prospective trials.
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