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111.
A Homozygous PDE6D Mutation in Joubert Syndrome Impairs Targeting of Farnesylated INPP5E Protein to the Primary Cilium 下载免费PDF全文
Sophie Thomas Kevin J. Wright Stéphanie Le Corre Alessia Micalizzi Marta Romani Avinash Abhyankar Julien Saada Isabelle Perrault Jeanne Amiel Julie Litzler Emilie Filhol Nadia Elkhartoufi Mandy Kwong Jean‐Laurent Casanova Nathalie Boddaert Wolfgang Baehr Stanislas Lyonnet Arnold Munnich Lydie Burglen Nicolas Chassaing Ferechté Encha‐Ravazi Michel Vekemans Joseph G. Gleeson Enza Maria Valente Peter K. Jackson Iain A. Drummond Sophie Saunier Tania Attié‐Bitach 《Human mutation》2014,35(1):137-146
Joubert syndrome (JS) is characterized by a distinctive cerebellar structural defect, namely the « molar tooth sign ». JS is genetically heterogeneous, involving 20 genes identified to date, which are all required for cilia biogenesis and/or function. In a consanguineous family with JS associated with optic nerve coloboma, kidney hypoplasia, and polydactyly, combined exome sequencing and mapping identified a homozygous splice‐site mutation in PDE6D, encoding a prenyl‐binding protein. We found that pde6d depletion in zebrafish leads to renal and retinal developmental anomalies and wild‐type but not mutant PDE6D is able to rescue this phenotype. Proteomic analysis identified INPP5E, whose mutations also lead to JS or mental retardation, obesity, congenital retinal dystrophy, and micropenis syndromes, as novel prenyl‐dependent cargo of PDE6D. Mutant PDE6D shows reduced binding to INPP5E, which fails to localize to primary cilia in patient fibroblasts and tissues. Furthermore, mutant PDE6D is unable to bind to GTP‐bound ARL3, which acts as a cargo‐release factor for PDE6D‐bound INPP5E. Altogether, these results indicate that PDE6D is required for INPP5E ciliary targeting and suggest a broader role for PDE6D in targeting other prenylated proteins to the cilia. This study identifies PDE6D as a novel JS disease gene and provides the first evidence of prenyl‐binding‐dependent trafficking in ciliopathies. 相似文献
112.
113.
含抗生素骨水泥假体在人工关节术后感染中的应用 总被引:3,自引:0,他引:3
目的 回顾分析含抗生素骨水泥假体(PROSTALAC)治疗人工关节置换术后感染的疗效。方法 对16例髋和膝关节置换术后感染的病例采用PROSTALAC方法,进行二期翻修治疗并进行随访。结果 16例髋和膝关节置换术后感染中,有14例于治疗后接受二期全髋或全膝关节翻修术,经平均46月的随访,感染无复发,成功率达87.5%。术后Harris髋关节评分平均达82.9分,膝关节评分平均达90.5分。结论 在PROSTALAC基础上进行的二期全髋和全膝关节翻修手术能成功地治疗人工关节术后感染,并且保持术后关节的功能。 相似文献
114.
Yung Chan Narendra N. Datta Kwong‐Yau Chan Safi Ur Rehman Christopher Yee‐Fat Poon John Ching‐Kwong Kwok 《Surgical Practice》2003,7(3):83-87
The present study retrospectively reviews our experience in 40 cases of vestibular schwannoma, operated between the years 1995 and 2002. All the patients underwent tumour resection either in sitting or in the Park bench position via the suboccipital retromastoid route. The position of the patient was selected arbitrarily. Precordial Doppler echocardiography was used to monitor air embolism. Operative results, including the size of the tumour, completeness of resection, anatomical and functional preservation of the facial nerve, operative complications and mortality were analysed and compared in these two operative positions. There was no statistically significant difference in terms of surgical results between these two groups. 相似文献
115.
0 引言 胃镜检查是上消化道疾病诊断的重要方法之一 .了解重复胃镜检查的原因及结果 ,有利于探讨疾病发生发展的基本规律 ,有利于发现诊断和治疗中存在的问题 ,从而提高对消化疾病的诊治水平 .1 材料和方法1.1 材料 随机抽检 1996 / 1998胃镜检查资料为调查对象7812例 ,其中行 2次以上胃镜检查者 937例 .调查内容包括性别、年龄、职业、主要症状和体征、病程、初步诊断、内镜检查时间、次数、内镜诊断、病理诊断、确诊时间 .1.2 方法 回顾性调查上述材料的临床特征 .列表统计研究对象一般情况的分布状况 ,计算各年龄段比例构成 ,各病… 相似文献
116.
Wayne K.W. Chan Kwong‐Yau Chan Ka‐Hung Pang Kong‐Ling Mak John C.K. Kwok 《Surgical Practice》2011,15(1):21-23
We present a case of histologically confirmed lipomatous meningioma, the first to our knowledge reported in Hong Kong. A 75‐year‐old woman presented to us with on and off dizziness for 1 month. Computed tomography (CT) of the brain showed an extra‐axial mass lesion containing fat and solid enhancing foci at her right frontal region. The definitive diagnosis could be made preoperatively. Postoperative histological examination of the tumour revealed the diagnosis of lipomatous meningioma. We have reviewed the literature and discussed the diagnostic clues, clinical presentation and pathology of this rare tumour. 相似文献
117.
CP Halvorsen SL Bilock C Pilo S-E Sonesson M Norman 《Acta paediatrica (Oslo, Norway : 1992)》2009,98(9):1468-1474
Aim: To perform a 10-year follow up of cardiac structure and function after twin-to-twin transfusion syndrome (TTTS) – a severe foetal circulatory complication associated with myocardial hypertrophy in the recipient twin.
Methods: Cardiac dimensions, systolic and diastolic function as assessed by echocardiography including flow and tissue Doppler velocimetry in 22 healthy survivors of TTTS with a mean age of 9.6 (7.2–11.8) years.
Results: The donor and recipient twin did not show any differences in end-diastolic ventricular size, interventricular septum thickness, diameter of right ventricular outflow tract, cardiac valves, coronary arteries or in systolic blood flow velocities. However, compared with the donors, the recipients had significantly lower E/A ratios because of lower E-waves in both mitral (−0.15 ± 0.10, p < 0.01) and tricuspid (−0.09 ± 0.07, p < 0.01) valves, indicating reduced early diastolic ventricular fillings compared with donors.
Conclusion: At school age, twins surviving TTTS had a cardiac structure and function within normal range. There were no differences in heart structure or systolic ventricular function between twins but, compared with the donor twin, we found a reduced early diastolic function in the recipient. 相似文献
Methods: Cardiac dimensions, systolic and diastolic function as assessed by echocardiography including flow and tissue Doppler velocimetry in 22 healthy survivors of TTTS with a mean age of 9.6 (7.2–11.8) years.
Results: The donor and recipient twin did not show any differences in end-diastolic ventricular size, interventricular septum thickness, diameter of right ventricular outflow tract, cardiac valves, coronary arteries or in systolic blood flow velocities. However, compared with the donors, the recipients had significantly lower E/A ratios because of lower E-waves in both mitral (−0.15 ± 0.10, p < 0.01) and tricuspid (−0.09 ± 0.07, p < 0.01) valves, indicating reduced early diastolic ventricular fillings compared with donors.
Conclusion: At school age, twins surviving TTTS had a cardiac structure and function within normal range. There were no differences in heart structure or systolic ventricular function between twins but, compared with the donor twin, we found a reduced early diastolic function in the recipient. 相似文献
118.
Po‐Lin Tseng Jing‐Houng Wang Hung‐Da Tung Chao‐Hung Hung Kwong‐Ming Kee Chien‐Hung Chen Kuo‐Chin Chang Chuan‐Mo Lee Chi‐Sin Changchien Pao‐Fei Chen Lin‐San Tsai Sheng‐Nan Lu 《Journal of gastroenterology and hepatology》2010,25(8):1426-1434
Background and Aim: The early detection of hepatocellular carcinoma (HCC) and opportunity to select appropriate treatment are important benefits of HCC screening. Our aim in the present study was to investigate the survival rate, prognostic factors and treatment effects in HCC patients of community‐based screening. Methods: Community‐based ultrasound (US) screening for HCC in adults with platelet counts (< 150 × 103/mm3) and/or alpha fetoprotein (AFP) > 20 ng/mL was conducted in 2002 and 2004. As per the Barcelona Clinic Liver Cancer (BCLC) stage, 90 cases of intermediate or earlier stage HCC were detected and 88 cases had sufficient information for analysis (49 men and 39 women, aged 65.8 ± 9.6 years). The tumor diameter was mostly less than 5 cm (76.1%). The follow up was continued until June 2008. Results: The 4‐year overall survival rate was 46.8%. Old age (≥ 70 years) (P = 0.046), later stage of HCC (intermediate vs earlier) (P = 0.012), low platelet count (< 100 × 103/mm3) (P = 0.013) and refusal of modern treatment (P = 0.026) were independent poor prognostic factors. Curative treatment increased survival in patients of all ages. Both curative treatment and transcatheter arterial embolization (TAE) increased survival in cases of intermediate HCC. However, treatment benefits were not found for patients with (very) early stage HCC. Conclusions: Early detection and prompt treatment of HCC leads to increased survival. For elderly patients this benefit was seen only for early stage cases receiving curative treatment. Differences between treatment types for patients with (very) early stage HCC might emerge with a longer follow‐up period. 相似文献
119.
Kwong‐Ming Kee Chi‐Ming Hung Jing‐Houng Wang Chao‐Hung Hung Pao‐Fei Chen Kuo‐Sin Lin Sheng‐Nan Lu 《Journal of gastroenterology and hepatology》2010,25(7):1289-1294
Background and Aim: This study attempted to clarify accuracy of acute hepatitis C (AHC) and its clinical characteristics. Methods: We reviewed 632 reported cases from national surveillance data of the Taiwan Center for Disease Control between 1995 and 2004, and reclassified diagnoses. A definite case was defined as alanine aminotransferase (ALT) > 10 × the upper limit of normal (ULN) with seroconversion of anti‐hepatitis C virus antibody (anti‐HCV). A probable case was defined as (i) seroconversion of anti‐HCV and/or elevated ALT levels; or (ii) anti‐HCV(+) but titers increased (from < 40 S/CO to ≥ 40 S/CO) and ALT > 10 × the ULN. A suspected case was defined as initial anti‐HCV(+) and ALT level > 10 × the ULN and/or jaundice. Excluded cases were defined as ALT levels less than 10 × ULN with initial positive anti‐HCV Ab. Results: A total of 310 (49%) cases were confirmed as AHC; these included 95 (15%) definite and 215 (34%) probable cases. Higher incidence rates and accuracy of AHC were demonstrated in the southern area significantly if compared with northern, eastern and central areas, respectively (all P < 0.05). On comparison between blood centers and hospitals, more AHC cases were found in Southern Taiwan than in other areas (157/73 vs 24/40, P < 0.001), younger mean age (33.3 ± 11.1 vs 49.3 ± 16.4, P < 0.001), lower ALT levels (263.1 ± 200.9 vs 1264.2 ± 706.8, P < 0.001) and male predominance (191/39 vs 46/18, P = 0.046). Conclusions: This study showed our reporting system over‐estimated the AHC diagnosis, which is also a common issue worldwide. Greater efforts are needed to establish appropriate reporting systems, as well as more supplemental methods to distinguish between prevalent and incident cases. 相似文献
120.
Wai Shan Chan Samantha Mei Che Pang Enid Wai Yung Kwong 《Journal of clinical nursing》2009,18(11):1565-1573
Aims and objectives. To assess and compare the predictive validity of the modified Braden and Braden scales and to identify which of the modified Braden subscales are predictive in assessing pressure ulcer risk among orthopaedic patients in an acute care setting. Background. Although the Braden scale has better predictive validity, literature has suggested that it can be used in conjunction with other pressure ulcer risk calculators or that some other subscales be added. To increase the predictive power of the Braden scale, a modified Braden scale by adding body build for height and skin type and excluding nutrition was developed. Design. A prospective cohort study. Method. A total of 197 subjects in a 106‐bed orthopaedic department of an acute care hospital in Hong Kong were assessed for their risk for pressure ulcer development by the modified Braden and Braden scales. Subsequently, daily skin assessment was performed to detect pressure ulcers. Cases were closed when pressure ulcers were detected. Results. Out of 197 subjects, 18 patients (9·1%) developed pressure ulcers. The area under the receiver operating characteristic curve for the modified Braden scale was 0·736 and for the Braden scale was 0·648. The modified Braden cut‐off score of 19 showed the best balance of sensitivity (89%) and specificity (62%). Sensory perception (Beta = ?1·544, OR=0·214, p = 0·016), body build for height (Beta = ?0·755, OR = 0·470, p = 0·030) and skin type (Beta = ?1·527, OR = 0·217, p = 0·002) were significantly predictive of pressure ulcer development. Conclusion. The modified Braden scale is more predictive of pressure ulcer development than the Braden scale. Relevance to clinical practice. The modified Braden scale can be adopted for predicting pressure ulcer development among orthopaedic patients in an acute care setting. Specific nursing interventions should be provided, with special attention paid to orthopaedic patients with impaired sensory perception, poor skin type and abnormal body build for height. 相似文献