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S Chasserot-Golaz P Hubert D Thiersé S Dirrig CJ Vlahos D Aunis MF Bader 《Canadian Metallurgical Quarterly》1998,70(6):2347-2356
Several lines of evidence suggest that phosphorylated products of phosphatidylinositol play critical functions in the regulation of membrane trafficking along the secretory pathway. To probe the possible involvement of phosphatidylinositol 3-kinase (PI 3-kinase) in regulated exocytosis, we have examined its subcellular distribution in cultured chromaffin cells by immunoreplica analysis and confocal immunofluorescence. We found that the PI 3-kinase heterodimer consisting of the regulatory and catalytic subunits was associated essentially with the subplasmalemmal cytoskeleton in both resting and nicotine-stimulated chromaffin cells. Attempts to immunoprecipitate PI 3-kinase with anti-phosphotyrosine antibodies failed, suggesting that the activity of PI 3-kinase was not modulated by tyrosine phosphorylation and/or physical interaction with SH2-containing proteins in stimulated chromaffin cells. LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one], a potent inhibitor of PI 3-kinase, produced a dose-dependent inhibition of catecholamine secretion evoked by various secretagogues. Furthermore, cytochemical experiments with rhodamine-labeled phalloidin revealed that LY294002 blocked the disassembly of cortical actin in chromaffin cells stimulated by a depolarizing concentration of potassium. Our results suggest that PI 3-kinase may be one of the important regulatory exocytotic components involved in the signaling cascade controlling actin rearrangements required for catecholamine secretion. 相似文献
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Selenium (Se)-dependent and -independent glutathione (GSH) peroxidases detoxify H2O2 and lipid hydroperoxides, which may mediate the teratogenicity of phenytoin and related xenobiotics. To test this hypothesis, CD-1 mice were placed on Se-deficient diets for 15, 25 or 40 days and bred so that the day of analysis corresponded to gestational day 11. In Se-replete control animals, embryonic peroxidase activities were only 5% of activities in maternal liver (P < .05). After 15 days of Se deprivation, maternal activities for H2O2 (reflecting Se-dependent peroxidase) and cumene hydroperoxide (CmOOH) (reflecting both Se-dependent and -independent peroxidases) were reduced to 20% (P < .05) and 35% of controls, respectively. At this time, the incidence of fetal cleft palates initiated by phenytoin (55 mg/kg intraperitoneally on gestational days 11, 12 and 13) was doubled, from 12% to 25% (P < .05). Selenite rescue (Na2SeO3, 350 micrograms/kg intraperitoneally on day 9) restored maternal and embryonic peroxidase activities and completely inhibited phenytoin-initiated postpartum lethality and fetal resorptions in animals that had been Se depleted for 15 days. After 40 days of Se deprivation, maternal and embryonic peroxidase/H2O2 activities were reduced to < 1% and 27% of Se-replete controls, respectively. In contrast, maternal peroxidase/CmOOH activity was increased to 70% of controls, reflecting induction of Se-independent peroxidase, compared with that with 15 days' depletion. Phenytoin-initiated cleft palates with 40 days' depletion appeared to be reduced (16%) compared with Se-replete controls (24%) (P < .07). In 40-day Se-depleted animals given selenite rescue, the 10% incidence of cleft palates was significantly lower than that in the 40-day Se-replete group (24%) but not the Se-depleted group (16%). This is the first demonstration of reduced Se-dependent GSH peroxidase activities in embryonic tissues with dietary Se-deprivation. The results implicate reactive oxygen species and lipid hydroperoxides in the mechanism of phenytoin teratogenicity and suggest that GSH peroxidases are important embryoprotective enzymes. 相似文献
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DL Zealear CL Rainey GD Herzon JL Netterville RH Ossoff 《Canadian Metallurgical Quarterly》1996,105(9):689-693
This study represents the first attempt to electrically pace the paralyzed human larynx. The goal was to determine if electrical stimulation of the posterior cricoarytenoid muscle could produce functional abduction of the vocal fold in pace with inspiration. An external apparatus was used to sense inspiration and reanimate the unilaterally paralyzed larynx of a thyroplasty patient. Stimuli were delivered through a needle electrode to locate and pace the abductor muscle. The magnitude of electrically induced abduction was comparable to spontaneous movement on the normal side. The abduction was appropriately timed with inspiration: this finding demonstrated that this simple pacing system could effectively modulate stimulation with patient respiration. 相似文献
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Randomized trial of breast self-examination in Shanghai: methodology and preliminary results 总被引:3,自引:0,他引:3
DB Thomas DL Gao SG Self CJ Allison Y Tao J Mahloch R Ray Q Qin R Presley P Porter 《Canadian Metallurgical Quarterly》1997,89(5):355-365
BACKGROUND: The efficacy of breast self-examination in helping to reduce mortality from breast cancer has not been rigorously demonstrated. PURPOSE: To assess efficacy, a large, randomized trial was initiated in Shanghai, China. METHODS: From October 1989 to October 1991, 267040 current and retired female employees associated with 520 factories in the Shanghai Textile Industry Bureau were randomly assigned on the basis of factory to either a self-examination instruction group (133375 women) or a control group (133665 women). The women were born within the period from 1925 through 1958. Women in the instruction group were given intensive training in breast self-examination, including the use of silicone breast models and personalized instruction, plus two subsequent reinforcement sessions and multiple reminders to practice the technique. Women in the control group were asked to attend training sessions on the prevention of low back pain. All women have been followed for the development of breast diseases and for death from breast cancer. RESULTS: A high level of participation during the first 4-5 years of the trial was documented among women in the instruction group. Randomly sampled women in this group demonstrated greater proficiency in detecting lumps in breast models than did randomly sampled women in the control group. Approximately equal numbers of breast cancers were detected in the two groups (331 in the instruction group and 322 in the control group) through 1994, which is the last year for which case-finding efforts have been completed. The breast cancers detected in the instruction group were not diagnosed at an appreciably earlier stage or smaller size than those in the control group. More benign breast lesions were detected in the instruction group than in the control group (1457 versus 623, respectively), suggesting a higher index of suspicion for women who received training. Cumulative breast cancer mortality rates through 5 years from entry into the study were nearly equivalent for the two groups. CONCLUSIONS: Breast self-examination has not led to a reduction in mortality from breast cancer in this study cohort in the first several years since the trial began. A shift toward the diagnosis of disease at a less advanced stage in women given instruction has also not been demonstrated. Longer follow-up of participants in this trial is required before final assessment can be made of the efficacy of breast self-examination. IMPLICATIONS: At this time, there is insufficient evidence to recommend for or against the teaching of breast self-examination. 相似文献
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This project reports the publication of a variety of existing curricular resources for emergency medicine on the global Internet in a format that allows hypertext links between related material, timely updates, and end-user feedback. Curricular elements were converted to Hypertext Markup Language with extensive links between related content. The completed document contains instructions for curriculum development, specific curricula for subspecialty areas within a residency, reading lists for subspecialty curricula, banks of images, and board-type questions with answers. Users are provided with a mechanism to provide immediate feedback to section editors with suggestions for changes, including new references. Access to all or part of the document can be controlled via passwords, but is potentially available to anyone with an Internet connection and a World Wide Web browser. The document may by viewed on the World Wide Web at: http:@www.brown.edu@Administration@emergency_Medicine@ curr.html. 相似文献
28.
DL Stokes 《Canadian Metallurgical Quarterly》1997,7(4):550-556
Electron microscopy is gradually revealing more and more about the structure of the calcium pump from the sarcoplasmic reticulum, Ca(2+)-ATPase. The most recent result reveals the ATP-binding site, and two different avenues are being pursued towards achieving a higher resolution structure. Although no such structures are currently available for phospholamban, various spectroscopies and site-directed mutagenesis have been combined to produce a compelling structural model for its regulation of Ca(2+)-ATPase. 相似文献
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