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991.
Bodo B. Beck Jennifer B. Phillips Malte P. Bartram Jeremy Wegner Michaela Thoenes Andrea Pannes Josephina Sampson Raoul Heller Heike Göbel Friederike Koerber Antje Neugebauer Andrea Hedergott Gudrun Nürnberg Peter Nürnberg Holger Thiele Janine Altmüller Mohammad R. Toliat Simon Staubach Kym M. Boycott Enza Maria Valente Andreas R. Janecke Tobias Eisenberger Carsten Bergmann Lars Tebbe Yang Wang Yundong Wu Andrew M. Fry Monte Westerfield Uwe Wolfrum Hanno J. Bolz 《Human mutation》2014,35(10):1153-1162
We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA), Joubert syndrome (JBTS), and polycystic kidney disease (PKD). Targeted next‐generation sequencing for excluding mutations in known LCA and JBTS genes, homozygosity mapping, and whole‐exome sequencing identified a homozygous missense variant, c.317G>C (p.Arg106Pro), in POC1B, a gene essential for ciliogenesis, basal body, and centrosome integrity. In silico modeling suggested a requirement of p.Arg106 for the formation of the third WD40 repeat and a protein interaction interface. In human and mouse retina, POC1B localized to the basal body and centriole adjacent to the connecting cilium of photoreceptors and in synapses of the outer plexiform layer. Knockdown of Poc1b in zebrafish caused cystic kidneys and retinal degeneration with shortened and reduced photoreceptor connecting cilia, compatible with the human syndromic ciliopathy. A recent study describes homozygosity for p.Arg106ProPOC1B in a family with nonsyndromic cone‐rod dystrophy. The phenotype associated with homozygous p.Arg106ProPOC1B may thus be highly variable, analogous to homozygous p.Leu710Ser in WDR19 causing either isolated retinitis pigmentosa or Jeune syndrome. Our study indicates that POC1B is required for retinal integrity, and we propose POC1B mutations as a probable cause for JBTS with severe PKD. 相似文献
992.
Eleanor L. Menzies John R.H. Archer Paul I. Dargan Mark C. Parkin Takahiro Yamamoto David M. Wood Robin A. Braithwaite Simon P. Elliott Andrew T. Kicman 《Drug testing and analysis》2019,11(9):1419-1430
The disposition of drugs and their metabolites have been extensively described in the literature, based primarily on the analysis of plasma and urine. However, there are more limited data on their disposition in whole blood, which is often the only specimen available in forensic investigations and cases of driving under the influence of drugs. In this study, we have, for the first time, established pharmacokinetic properties of cocaine (COC) and its metabolites from concurrently collected whole blood and plasma samples, following a single 100 mg dose of cocaine hydrochloride administered via nasal insufflation to seven healthy volunteers. The median Cmax of COC and its major metabolites, benzoylecgonine (BZE) and ecgonine methyl ester (EME), were closely related in whole blood and plasma. The median Cmax for COC in plasma was 379.7 ng/mL (347.5–517.7) and 344.24 ng/mL (271.6–583.2) in whole blood. The median Cmax for BZE in plasma was 441.2 ng/mL (393.6–475. and 371.18 ng/mL (371.1–477.3) in whole blood, EME was 105.5 ng/mL (93.6–151.8) in plasma and 135.5 ng/mL (87.8–183) in whole blood. Calculated medians of the whole blood to plasma ratio of COC (0.76), BZE (0.98) and EME (1.02) of approximately 1, strongly suggesting that the erythrocyte cell wall presents no barrier to COC and its metabolites. Furthermore, whole blood and plasma concentrations of COC were strongly correlated (R2 = 0.0914 R = 0.956, p < 0.0001), as was BZE (R2 = 0.0932 R = 0.965, p < 0.0001) and EME (R2 = 0.0964R = 0.928, p < 0.0001). The minor oxidative metabolite norcocaine (NCOC) was detected in both whole blood and plasma at concentrations between 1 and 5 ng/mL within 60–180 minutes, suggesting that NCOC could be indicator of recent COC administration. Data from this study have shown for the first time that COC and its metabolites BZE and EME are evenly distributed between plasma and whole blood following controlled single‐dose intranasal COC administration. 相似文献
993.
Roza Badr Eslam Florian Posch Irene M. Lang Thomas Gremmel Beate Eichelberger Cihan Ay Simon Panzer 《Journal of cardiovascular translational research》2014,7(1):126-132
We studied the association of thrombin generation potential with platelet protease activated receptor (PAR)-1 regulation and platelet activation in 52 stable coronary artery disease patients on continuous therapy with aspirin and clopidogrel (n?=?42) or prasugrel (n?=?10). Compared to controls, peak thrombin generation potential was elevated in only 11 patients (p?>?0.05), while F1.2 was elevated in 26 patients (p?<?0.0001). PAR-1 and thrombin inducible P-selectin expression were significantly elevated in patients compared to controls (p?<?0.001). There were no significant correlations between levels of thrombin generation potential or F1.2 and PAR-1 regulation. However, there was a significant inverse correlation between levels of peak thrombin generation potential and in vitro thrombin-inducible expression of P-selectin (p?=?0.002), suggesting in vivo depletion of platelet alpha granules due to ongoing platelet activation. 相似文献
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997.
Lijoy K. Mathew Nicolas Skuli Vera Mucaj Samuel S. Lee Pascal O. Zinn Pratheesh Sathyan Hongxia Z. Imtiyaz Zhongfa Zhang Ramana V. Davuluri Shilpa Rao Sriram Venneti Priti Lal Justin D. Lathia Jeremy N. Rich Brian Keith Andy J. Minn M. Celeste Simon 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(1):291-296
998.
Patients with neuromuscular conditions are frequently seen in final professional clinical examinations as they have good clinical signs, which often point towards the underlying diagnosis. This paper outlines some of the most common neuromuscular disorders that you are likely to come across in orthopaedic practise. 相似文献
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