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91.
JR Henkel G Apodaca Y Altschuler S Hardy OA Weisz 《Canadian Metallurgical Quarterly》1998,9(9):2477-2490
The function of acidification along the endocytic pathway is not well understood, in part because the perturbants used to modify compartmental pH have global effects and in some cases alter cytoplasmic pH. We have used a new approach to study the effect of pH perturbation on postendocytic traffic in polarized Madin-Darby canine kidney (MDCK) cells. Influenza M2 is a small membrane protein that functions as an acid-activated ion channel and can elevate the pH of the trans-Golgi network and endosomes. We used recombinant adenoviruses to express the M2 protein of influenza virus in polarized MDCK cells stably transfected with the polymeric immunoglobulin (Ig) receptor. Using indirect immunofluorescence and immunoelectron microscopy, M2 was found to be concentrated at the apical plasma membrane and in subapical vesicles; intracellular M2 colocalized partly with internalized IgA in apical recycling endosomes as well as with the trans-Golgi network marker TGN-38. Expression of M2 slowed the rate of IgA transcytosis across polarized MDCK monolayers. The delay in transport occurred after IgA reached the apical recycling endosome, consistent with the localization of intracellular M2. Apical recycling of IgA was also slowed in the presence of M2, whereas basolateral recycling of transferrin and degradation of IgA were unaffected. By contrast, ammonium chloride affected both apical IgA and basolateral transferrin release. Together, our data suggest that M2 expression selectively perturbs acidification in compartments involved in apical delivery without disrupting other postendocytic transport steps. 相似文献
92.
J Whittle CJ Lin JR Lave MJ Fine KM Delaney DZ Joyce WW Young WN Kapoor 《Canadian Metallurgical Quarterly》1998,36(7):977-987
OBJECTIVES: The authors describe the relation of provider characteristics to processes, costs, and outcomes of medical care for elderly patients hospitalized for community-acquired pneumonia. METHODS: Using Medicare claims data, Medicare beneficiaries discharged from Pennsylvania hospitals during 1990 with community-acquired pneumonia were identified. Claims data were used to ascertain mortality, readmissions, use of procedures and physician consultations, and the costs of care. The relationship of these measures to provider characteristics was analyzed using regression techniques to adjust for patient characteristics, including comorbidity and microbial etiology. RESULTS: Among 22,294 pneumonia episodes studied, 30-day mortality was 17.0%. After adjusting for patient characteristics, 30-day mortality and readmission rates were unrelated to hospital teaching status or urban location or to physician specialty. Use of procedures and physician consultations was more common and costs were 11% higher among patients discharged from teaching hospitals compared with nonteaching hospitals. Similarly, costs were 15% higher at urban hospitals compared with rural hospitals. General internists and medical subspecialists used more procedures and had higher costs than family practitioners. CONCLUSIONS: Processes and costs of care for community-acquired pneumonia varied by provider characteristics, but neither mortality nor readmission rates did. These differences cannot be explained by clinical variables in the database. Further studies should determine whether less costly patterns of care for pneumonia, and perhaps other conditions, could replace more costly ones without compromising patient outcomes. 相似文献
93.
BACKGROUND AND PURPOSE: Norway has the highest reported incidence of hip fractures in western Europe. Little is known about the epidemiology of falls in Norway where the winter season is long and dark. The objective of this work was to study reported falls and their consequences among elderly Norwegians living at home. METHODS: A cross-sectional design was used for the study. Interviews were performed in the homes of 431 subjects, aged 67-97 years, living at home. Information on falling was gathered through six questions: whether the subject had fallen during the last six months, and if so, how many falls they had, where the last fall occurred, its perceived reason, the activity the subject had been engaged in when the fall occurred, and the resulting injury. RESULTS: In all, 24.1% of subjects reported falling during the last six months, and 9.5% had suffered more than one fall. Falls were most frequently linked to external events (63.1%). Outdoor falls were more frequent (59.0%; 95% CI = 51.2-82.0) than indoor falls. Older subjects were associated with more frequent indoor falls (p < 0.05), but gender was not significant. Fifty-one per cent of subjects had fallen while walking and 53% had suffered an injury from the last fall. In 13.4% of the women and 16.2% of the men, the last fall had resulted in a fracture. CONCLUSIONS: Compared to the results of other studies from industrialized Western countries, a similar crude fall rate, similar frequency and similar type of injury were found. However, in contrast to other studies, no gender difference was observed with regard to falling, place of falling and fracture rate. 相似文献
94.
OBJECTIVE: Prednisolone reduced the progression of joint destruction over 2 yr in early, active rheumatoid arthritis. The response to discontinuation of prednisolone under double-blind conditions is now reported. METHODS: A randomized, double-blind, placebo-controlled trial of prednisolone 7.5 mg daily in addition to routine medication over 2 yr in 128 patients with early rheumatoid arthritis, using radiological progression (changes in the Larsen score) and the development of erosions as primary outcome measures. Study medication was blindly discontinued and follow-up maintained for a further year. Other assessments included disability, joint inflammation, pain and the acute-phase response. RESULTS: Similar results were obtained when all available radiographs were included for each year of assessment (maximum 114) and when only patients with radiographs at all time points were included (75 patients). In these 75, the mean progression in the prednisolone group was 0.21 Larsen units in year 1, 0.04 units in year 2 and 1.01 units in year 3 (P = 0.587, 0.913 and 0.039 for change within each year, respectively). The equivalent placebo group means were 2.34, 1.00 and 1.63 Larsen units (P = 0.001, 0.111 and 0.012; difference between groups: 2.13, 0.96 and 0.67 units, P = 0.082, 0.02 and 0.622). The percentage of hands which had erosions at each time point was: prednisolone group: 27.8, 29.2, 34.7 and 39.2; placebo group: 28.2, 48.7, 59.0 and 66.5. There was little evidence for a flare in clinical symptoms after discontinuation of prednisolone. CONCLUSION: Joint destruction resumed after discontinuation of prednisolone. This corroborates the previously reported therapeutic effect and challenges current concepts of disease pathogenesis. 相似文献
95.
JR Council EJ Smith J Kaster-Bundgaard BA Gladue 《Canadian Metallurgical Quarterly》1997,39(4):258-265
We surveyed hypnosis researchers and Institutional Review Boards (IRBs) with regard to the ethical evaluation of research protocols. Researchers and IRB administrators were independently surveyed within the same institutions. Both objective and free response items were used to address substantive issues such as deception and at-risk populations, as well as practical matters such as paperwork. Parallel questions allowed a point-counterpoint between researchers and IRBs. Overall, the results suggest that IRBs do not treat hypnosis research differently than other types of research. We end with recommendations for facilitating interactions between hypnosis researchers and their IRBs. 相似文献
96.
JR Nofer M Walter B Kehrel S Wierwille M Tepel U Seedorf G Assmann 《Canadian Metallurgical Quarterly》1998,18(6):861-869
We demonstrate that physiological concentrations of HDL3 inhibit the thrombin-induced platelet fibrinogen binding and aggregation in a time- and concentration-dependent fashion. The underlying mechanism includes HDL3-mediated inhibition of phosphatidylinositol 4,5-bis-phosphate turnover, 1,2-diacylglycerol and inositol 1,4,5-tris-phosphate formation, and intracellular calcium mobilization. The inhibitory effects of HDL3 on inositol 1,4,5-tris-phosphate formation and intracellular calcium mobilization were abolished after covalent modification of HDL3 with dimethylsuberimidate. Furthermore, they could be blocked by calphostin C and bis-indolylmaleimide, 2 highly selective and structurally unrelated protein kinase C inhibitors. However, the inhibitory effects of HDL3 were not blocked by H89, a protein kinase A inhibitor. In addition, HDL3 failed to induce cAMP formation but stimulated the phosphorylation of the protein kinase C 40- to 47-kD major protein substrate. We observed a close temporal relationship between the HDL3-mediated inhibition of thrombin-induced inositol 1,4,5-tris-phosphate formation, intracellular calcium mobilization, and fibrinogen binding and the phosphorylation of the protein kinase C 40- to 47-kD major protein substrate. Taken together, these findings indicate that the HDL3-mediated inhibition of thrombin-induced fibrinogen binding and aggregation occurs via inhibition of phosphatidylinositol 4,5-bis-phosphate turnover and formation of 1,2-diacylglycerol and inositol 1,4,5-tris-phosphate. Protein kinase C may be involved in this process. 相似文献
97.
Blastomyces dermatitidis, a dimorphic broad-based budding yeast endemic to the Mississippi River Valley region, is responsible for morbidity in humans via inhalation and dissemination. The response of acute lung injury, which produces an illness with serious morbidity and an approximately 50% mortality, uncommonly occurs. Diagnosis can be difficult, and a high index of suspicion should be maintained in endemic regions for patients with acute lung injury of uncertain etiology, especially if their condition deteriorates on broad-spectrum antimicrobial and antitubercular therapy and they have a previous insidious respiratory complaint and constitutional symptoms. Diagnosis should be aggressively pursued and treatment with amphotericin B (0.6 to 0.8 mg/kg/day) initiated as early as possible. 相似文献
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The 9th International Congress on Genes, Gene Families, and Isozymes marked a historic transition in the series formerly known as the International Congress on Isozymes. The name of the congress was changed to reflect the broadened scope of this field and the new directions in which it is moving. To recognize and promote this transition, a number of new features were incorporated into this congress. Accordingly, the broad-based program featured preeminent biologists from 29 different countries. A total of 350 people attended the congress. A special new feature of this congress was the Student/Fellow Program, which was designed to enhance participation by advanced undergraduate and graduate students and postdoctoral fellows. This congress celebrated the progress that has occurred during the past 40 years beginning with studies of isozymes and leading into studies of specific genes and gene families. As we move into the next millennium, it is clear that our field is strongly positioned and will continue to be the focus of exciting and important new research. 相似文献