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排序方式: 共有522条查询结果,搜索用时 46 毫秒
1.
Bong Jik Kim Dong‐Kyu Kim Jin Hee Han Jayoung Oh Ah Reum Kim Chung Lee Nayoung KD Kim Hye‐Rim Park Min Young Kim Sejoon Lee Seungmin Lee Doo Yi Oh Woong‐Yang Park Sungjin Park Byung Yoon Choi 《Human mutation》2019,40(5):525-531
Otoancorin (OTOA), encoded by OTOA, is required for the development of the tectorial membrane in the inner ear. Mutations in this gene cause nonsyndromic hearing loss (DFNB22). The molecular mechanisms underlying most DFNB22 remain poorly understood. Disruption of glycosylphosphatidylinositol (GPI) anchorage has been assumed to be the pathophysiology mandating experimental validation. From a Korean deaf family, we identified two trans OTOA variants (c.1320 + 5 G>C and p.Gln589ArgfsX55 [NM_144672.3]) . The pathogenic potential of c.1320 + 5 G>C was confirmed by a minigene splicing assay. To experimentally determine the GPI anchorage, wild‐type (WT) and mutant OTOA harboring p.Gln589ArgfsX55 were expressed in HEK293T cells. The mutant OTOA with p.Gln589ArgfsX55 resulted in an uncontrolled release of OTOA into the medium in contrast with phosphatidylinositol‐specific phospholipase C‐induced controlled release of WT OTOA from the cell surface. Together, the results of this reverse translational study confirmed GPI‐anchorage of OTOA and showed that downstream sequences from the 589th amino acid are critical for GPI‐anchorage. 相似文献
2.
O'Halloran P 《Nursing in critical care》2008,13(5):276-277
Objective: There is growing evidence that low nurse staffing jeopardizes quality of patient care. The objective of the study was to determine whether low staffing level increases the infection risk in critical care. Design: Observational, single‐centre, prospective cohort study. Setting: Medical intensive care unit of the University of Geneva Hospitals, Switzerland. Patients: All patients admitted over a 4‐year period. Interventions: None. Measurements and main results: Study variables included all infections acquired in critical care, daily nurse‐to‐patient ratio, demographic characteristics, admission diagnosis and severity score, comorbidities, daily individual exposure to invasive devices and selected drugs. Of a cohort of 1883 patients totalling 10 637 patient‐days, 415 (22%) developed at least one health care‐associated infection (HCAI) while in critical care. Overall infection rate was 64·5 episodes per 1000 patient‐days. Infected patients experienced higher mortality with a longer duration of stay both in critical care and in the hospital than non‐infected patients (all p < 0·001). Median 24‐h nurse‐to‐patient ratio was 1·9. Controlling for exposure to central venous catheter, mechanical ventilation, urinary catheter and antibiotics, we found that higher staffing level was associated with a >30% infection risk reduction (incidence rate ratio, 0·69; 95% CI: 0·50–0·95). We estimated that 26·7% of all infections could be avoided if the nurse‐to‐patient ratio was maintained >2·2. Conclusions: Staffing is a key determinant of HCAI in critically ill patients. Assuming causality, a substantial proportion of all infections could be avoided if nurse staffing were to be maintained at a higher level. Abstract reprinted from Critical Care Medicine, volume 35, Hugonnet S et al., ‘The effect of workload on infection risk in critically ill patients.’, pages 76–81. © 2007, reproduced with permission from Lippincott Williams & Wilkins. 相似文献
3.
Anniek KD Visser Nisha K Ramakrishnan Antoon TM Willemsen Valentina Di Gialleonardo Erik FJ de Vries Ido P Kema Rudi AJO Dierckx Aren van Waarde 《Journal of cerebral blood flow and metabolism》2014,34(1):118-125
The PET tracer [11C]5-hydroxytryptophan ([11C]5-HTP), which is converted to [11C]5-hydroxytryptamine ([11C]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [11C]5-HTP in rat? Male rats were scanned with [11C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [11C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [11C]5-HTP uptake, and the k3. This was unexpected as NSD 1015 directly inhibits the enzyme converting [11C]5-HTP to [11C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [11C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents. 相似文献
4.
In diffusion-weighted imaging, multishot acquisitions are problematic due to intershot inconsistencies of the phase caused by motion during the diffusion-encoding gradients. A model for the motion-induced phase errors in diffusion-weighted-MRI of the brain is presented, in which rigid-body and nonrigid-body motion are separated. In the model, it is assumed that nonrigid-body motion is due to cardiac pulsation, and that the motion patterns are repeatable from beat-to-beat. To test the validity of this assumption, the repeatability of nonrigid-body motion-induced phase errors is quantified in three healthy volunteers. Nonrigid-body motion-induced phase was found to significantly correlate (P < 0.05) with pulse-oximeter waveforms in ~83% of the pixels tested across all slices and subjects. 相似文献
5.
This paper describes the curriculum model developed for an ambitious interprofessional education programme for health and social care professions implemented in two universities in the south of England (the New Generation Project). An outline of how the New Generation Project has interpreted the meaning of interprofessional learning is presented first. This is followed by an outline of the structure of the programme, describing both learning in common and interprofessional learning components. The pedagogies underpinning this curriculum initiative are presented and an integrated pedagogical model, facilitated collaborative interprofessional learning, is proposed. The New Generation Project curriculum is then discussed as an extension of an established typology of interprofessional education. 相似文献
6.
7.
Connie W Tsao Mark E Josephson Thomas H Hauser T David O'Halloran Anupam Agarwal Warren J Manning Susan B Yeon 《Journal of cardiovascular magnetic resonance》2008,10(1):1-7
Purpose
In mitral valve prolapse, determining whether the valve is suitable for surgical repair depends on the location and mechanism of regurgitation. We assessed whether cardiovascular magnetic resonance (CMR) could accurately identify prolapsing or flail mitral valve leaflets and regurgitant jet direction in patients with known moderate or severe mitral regurgitation.Methods
CMR of the mitral valve was compared with trans-thoracic echocardiography (TTE) in 27 patients with chronic moderate to severe mitral regurgitation due to mitral valve prolapse. Contiguous long-axis high temporal resolution CMR cines perpendicular to the valve commissures were obtained across the mitral valve from the medial to lateral annulus. This technique allowed systematic valve inspection and mapping of leaflet prolapse using a 6 segment model. CMR mapping was compared with trans-oesophageal echocardiography (TOE) or surgical inspection in 10 patients.Results
CMR and TTE agreed on the presence/absence of leaflet abnormality in 53 of 54 (98%) leaflets. Prolapse or flail was seen in 36 of 54 mitral valve leaflets examined on TTE. CMR and TTE agreed on the discrimination of prolapse from flail in 33 of 36 (92%) leaflets and on the predominant regurgitant jet direction in 26 of the 27 (96%) patients. In the 10 patients with TOE or surgical operative findings available, CMR correctly classified presence/absence of segmental abnormality in 49 of 60 (82%) leaflet segments.Conclusion
Systematic mitral valve assessment using a simple protocol is feasible and could easily be incorporated into CMR studies in patients with mitral regurgitation due to mitral valve prolapse. 相似文献8.
目的:目前有关骨髓间充质干细胞向内皮细胞诱导分化的研究较少。本实验分离和培养人骨髓间充质干细胞,用带有VEGF165的质粒转染人骨髓间充质干细胞,探讨血管内皮生长因子对其体外诱导分化的作用。
方法:实验于2005—04/2006—04在吉林大学人兽共患病教育部重点实验室完成。取成人的已排除血液系统肿瘤疾病的新鲜骨髓(自愿提供),采用Percoll梯度分离培养骨髓间充质干细胞,于倒置显微镜下观察细胞形态变化和生长情况。原代细胞培养至增殖接近融合状态时,单克隆培养法分离传代培养,扩增骨髓间充质干细胞。采用流式细胞术检测细胞免疫学表型。在原核细胞大肠杆菌DH5α中复制扩增和提取,纯化、克隆pcDNA3.0-VEGF165质粒。用脂质体转染法转染骨髓间充质干细胞:应用流式细胞术检测诱导后骨髓间充质干细胞免疫学表型变化j并采用免疫荧光染色鉴定转染情况,并设质粒空载和未转染的骨髓间充质干细胞为对照。
结果:人骨髓间充质干细胞原代培养1周后,造血细胞消失,贴壁细胞体积增大,呈现梭形外观,有粗大的细胞突起伸出。2周后细胞融合成单层,梭形突起变长,排列有明显的方向性,细胞排列成旋涡状、网状、辐射状。流式细胞术显示,人骨髓间充质干细胞免疫学表型CD44、CD29阳性,CD34、CD31、CD45阴性。VEGF165诱导骨髓间充质千细胞后CD44表达明显降低,CD31明显升高。免疫荧光染色显示,用FITC标记后的VEGF抗体使细胞显现绿色荧光,用cy3标记的CD31抗体使细胞显现了红色荧光。
结论:转染后的骨髓间充质干细胞细胞表型发生明显转变,CD31表达率明显增高,呈现典型的内皮细胞的表型特征,这说明骨髓间充质干细胞具有向内皮细胞分化的潜能。 相似文献
9.
10.
TR Fricke BA Holden DA Wilson G Schlenther KS Naidoo S Resnikoff KD Frick 《Bulletin of the World Health Organization》2012,90(10):728-738