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991.
992.
Transgenic cattle produced by reverse-transcribed gene transfer in oocytes 总被引:7,自引:0,他引:7
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Anthony W. S. Chan E. Jane Homan Linda U. Ballou Jane C. Burns Robert D. Bremel 《Proceedings of the National Academy of Sciences of the United States of America》1998,95(24):14028-14033
A critical requirement for integration of retroviruses, other than HIV and possibly related lentiviruses, is the breakdown of the nuclear envelope during mitosis. Nuclear envelope breakdown occurs during mitotic M-phase, the envelope reforming immediately after cell division, thereby permitting the translocation of the retroviral preintegration complex into the nucleus and enabling integration to proceed. In the oocyte, during metaphase II (MII) of the second meiosis, the nuclear envelope is also absent and the oocyte remains in MII arrest for a much longer period of time compared with M-phase in a somatic cell. Pseudotyped replication-defective retroviral vector was injected into the perivitelline space of bovine oocytes during MII. We show that reverse-transcribed gene transfer can take place in an oocyte in MII arrest of meiosis, leading to production of offspring, the majority of which are transgenic. We discuss the implications of this mechanism both as a means of production of transgenic livestock and as a model for naturally occurring recursive transgenesis. 相似文献
993.
994.
Factors predicting progression of gastric intestinal metaplasia: results of a randomised trial on Helicobacter pylori eradication 总被引:13,自引:0,他引:13
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BACKGROUND AND AIMS: Gastric intestinal metaplasia (IM) is generally considered to be a precancerous lesion in the gastric carcinogenesis cascade. This study identified the risk factors associated with progression of IM in a randomised control study. SUBJECTS AND METHODS: A total of 587 Helicobacter pylori infected subjects were randomised to receive a one week course of anti-Helicobacter therapy (omeprazole, amoxicillin, and clarithromycin (OAC)) or placebo. Subjects underwent endoscopy with biopsy at baseline and at five years. Severity of IM was graded according to the updated Sydney classification and progression was defined as worsening of IM scores at five years in either the antrum or corpus, or development of neoplasia. Backward stepwise multiple logistic regression was used to identify independent risk factors associated with IM progression. RESULTS: Of 435 subjects (220 in the OAC and 215 in the placebo group) available for analysis, 10 developed gastric cancer and three had dysplasia. Overall progression of IM was noted in 52.9% of subjects. Univariate analysis showed that persistent H pylori infection, age >45 years, male subjects, alcohol use, and drinking water from a well were significantly associated with IM progression. Duodenal ulcer and OAC treatment were associated with a reduced risk of histological progression. Progression of IM was more frequent in those with more extensive and more severe IM at baseline. With multiple logistic regression, duodenal ulcer (odds ratio (OR) 0.23 (95% confidence interval (CI) 0.09-0.58)) was found to be an independent protective factor against IM progression. Conversely, persistent H pylori infection (OR 2.13 (95% CI 1.41-3.24)), age >45 years (OR 1.92 (95% CI 1.18-3.11)), alcohol use (OR 1.67 (95% CI 1.07-2.62)), and drinking water from a well (OR 1.74 (95% CI 1.13-2.67)) were independent risk factors associated with IM progression. CONCLUSION: Eradication of H pylori is protective against progression of premalignant gastric lesions. 相似文献
995.
996.
A 3-year-old boy presented with brainstem astrocytoma and central alveolar hypoventilation syndrome. Contrast MRI of the brain showed that the tumor involved the cerebellum, with compression of brainstem, and resolved after surgical resection. Polysomnography performed before and after total tumor resection showed significant improvement in nocturnal respiratory rate, respiratory disturbance index, and oxygen desaturation. It is apparent that central alveolar hypoventilation syndrome secondary to brainstem tumor may improve after surgical resection for those with favorable anatomic location and histology. Serial polysomnography and MRI scans are useful for diagnosis and in the management plan, and to monitor progress. 相似文献
997.
Ashish Correa Achint Patel Kinsuk Chauhan Harshil Shah Aparna Saha Mihir Dave Priti Poojary Abhishek Mishra Narender Annapureddy Shaman Dalal Ioannis Konstantinidis Renu Nimma Shiv Kumar Agarwal Lili Chan Girish Nadkarni Sean Pinney 《Journal of cardiac failure》2018,24(7):442-450
Background
Dialysis-requiring acute kidney injury (D-AKI) is a serious complication in hospitalized heart failure (HF) patients. However, data on national trends are lacking after 2002.Methods
We used the Nationwide Inpatient Sample (2002–2013) to identify HF hospitalizations with and without D-AKI. We analyzed trends in incidence, in-hospital mortality, length of stay (LoS), and cost. We calculated adjusted odds ratios (aORs) for predictors of D-AKI and for outcomes including in-hospital mortality and adverse discharge (discharge to skilled nursing facilities, nursing homes, etc).Results
We identified 11,205,743 HF hospitalizations. Across 2002–2013, the incidence of D-AKI doubled from 0.51% to 1.09%. We found male sex, younger age, African-American and Hispanic race, and various comorbidities and procedures, such as sepsis and mechanical ventilation, to be independent predictors of D-AKI in HF hospitalizations. D-AKI was associated with higher odds of in-hospital mortality (aOR 2.49, 95% confidence interval [CI] 2.36–2.63; P?<?.01) and adverse discharge (aOR 2.04, 95% CI 1.95–2.13; P?<?.01). In-hospital mortality and attributable risk of mortality due to D-AKI decreased across 2002–2013. LoS and cost also decreased across this period.Conclusions
The incidence of D-AKI in HF hospitalizations doubled across 2002–2013. Despite declining in-hospital mortality, LoS, and cost, D-AKI was associated with worse outcomes. 相似文献998.
Previous studies have demonstrated that microvolt T-wave alternans (MTWA) screening effectively risk-stratifies patients with ischemic cardiomyopathy. Whether the prognostic utility of MTWA diminishes over 3 years of follow-up remains unknown. In this study, a prospective cohort of 768 patients with ischemic cardiomyopathy (left ventricular ejection fraction <35%) and no previous sustained ventricular arrhythmia was developed, of whom 514 (67%) screened MTWA nonnegative (positive and indeterminate). The mean follow-up period was 18 +/- 11 months. The primary end point was all-cause mortality and appropriate implantable cardioverter-defibrillator shocks. Stratified Cox regression analyses (by implantable cardioverter-defibrillator status) estimated the predictive power of MTWA within each year of follow-up and determined whether this diminished over time. There were 99 deaths (MTWA negative: 21 [8.3%]; MTWA nonnegative: 78 [15.2%]) and 33 appropriate implantable cardioverter-defibrillator shocks (MTWA negative: 3 [4.0%]; MTWA nonnegative: 30 [9.5%]). After multivariate adjustment, a nonnegative MTWA test result was associated with a greater than twofold increased risk for events in each of the 3 years of follow-up (year 1: stratified hazard ratio 2.19, 95% confidence interval 1.10 to 4.34, p = 0.03; year 2: stratified hazard ratio 3.36, 95% confidence interval 1.28 to 8.83, p = 0.01; year 3: stratified hazard ratio 2.06, 95% confidence interval 0.81 to 5.22, p = 0.13). There were no significant interactions between the time periods (year 1 vs year 2: p = 0.47; year 1 vs year 3: p = 0.92). In conclusion, MTWA reliably and consistently predicts mortality and arrhythmic risk throughout the first 2 to 3 years of follow-up. Although these findings need further validation, they suggest that rescreening with MTWA may not need to be performed more frequently than once every 2 years. 相似文献
999.
The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia 总被引:6,自引:0,他引:6
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Junge CE Sugawara T Mannaioni G Alagarsamy S Conn PJ Brat DJ Chan PH Traynelis SF 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(22):13019-13024
The serine proteases tissue plasminogen activator, plasmin, and thrombin and their receptors have previously been suggested to contribute to neuronal damage in certain pathological situations. Here we demonstrate that mice lacking protease-activated receptor 1 (PAR1) have a 3.1-fold reduction in infarct volume after transient focal cerebral ischemia. Intracerebroventricular injection of PAR1 antagonist BMS-200261 reduced infarct volume 2.7-fold. There are no detectable differences between PAR1-/- and WT mice in cerebrovascular anatomy, capillary density, or capillary diameter, demonstrating that the neuroprotective phenotype is not likely related to congenital abnormalities in vascular development. We also show that the exogenously applied serine proteases thrombin, plasmin, and tissue plasminogen activator can activate PAR1 signaling in brain tissue. These data together suggest that if blood-derived serine proteases that enter brain tissue in ischemic situations can activate PAR1, this sequence of events may contribute to the harmful effects observed. Furthermore, PAR1 immunoreactivity is present in human brain, suggesting that inhibition of PAR1 may provide a novel potential therapeutic strategy for decreasing neuronal damage associated with ischemia and blood-brain barrier breakdown. 相似文献
1000.