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Simon Mead, Matthew Burnell, Jessica Lowe, Andrew Thompson, Ana Lukic, Marie-Claire Porter, Christopher Carswell, Diego Kaski, Janna Kenny, Tze How Mok, Nina Bjurstrom, Edit Franko, Michele Gorham, Ronald Druyeh, Jonathan D F Wadsworth, Zane Jaunmuktane, Sebastian Brandner, Harpreet Hyare, Peter Rudge, A Sarah Walker, John Collinge
IMPORTANCE: A major challenge for drug development in neurodegenerative diseases is that adequately powered efficacy studies with meaningful end points typically require several hundred participants and long durations. Prion diseases represent the archetype of brain diseases caused by protein misfolding, the most common subtype being sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia. There is no well-established trial method in prion disease. OBJECTIVE: To establish a more powerful and meaningful clinical trial method in sCJD...
April 2016: JAMA Neurology
Anil Purohit, Adam G Rokita, Xiaoqun Guan, Biyi Chen, Olha M Koval, Niels Voigt, Stefan Neef, Thomas Sowa, Zhan Gao, Elizabeth D Luczak, Hrafnhildur Stefansdottir, Andrew C Behunin, Na Li, Ramzi N El-Accaoui, Baoli Yang, Paari Dominic Swaminathan, Robert M Weiss, Xander H T Wehrens, Long-Sheng Song, Dobromir Dobrev, Lars S Maier, Mark E Anderson
BACKGROUND: Atrial fibrillation (AF) is a growing public health problem without adequate therapies. Angiotensin II and reactive oxygen species are validated risk factors for AF in patients, but the molecular pathways connecting reactive oxygen species and AF are unknown. The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has recently emerged as a reactive oxygen species-activated proarrhythmic signal, so we hypothesized that oxidized CaMKIIδ could contribute to AF. METHODS AND RESULTS: We found that oxidized CaMKII was increased in atria from AF patients compared with patients in sinus rhythm and from mice infused with angiotensin II compared with mice infused with saline...
October 15, 2013: Circulation
Sandra J Shultz, Randy J Schmitz, John R Cone, Timothy J Copple, Melissa M Montgomery, Michele L Pye, Amanda J Tritsch
PURPOSE: This study aimed to examine changes in sagittal (AP LAX), frontal (VV LAX), and transverse (IER LAX) plane knee laxity in men and women during an intermittent exercise protocol (IEP) simulating the intensity and duration of a soccer match. METHODS: Intercollegiate/club athletes (29 females and 30 males) were measured on AP LAX (-90 to 130 N) before and after warm-up and every 15 min during and for 1 h after the IEP. VV LAX (± 10 N · m) and IER LAX (± 5 N · m) were measured before and after warm-up, at the end of each 45-min half, and at 30 min after exercise...
August 2013: Medicine and Science in Sports and Exercise
Min Luo, Xiaoqun Guan, Elizabeth D Luczak, Di Lang, William Kutschke, Zhan Gao, Jinying Yang, Patric Glynn, Samuel Sossalla, Paari D Swaminathan, Robert M Weiss, Baoli Yang, Adam G Rokita, Lars S Maier, Igor R Efimov, Thomas J Hund, Mark E Anderson
Diabetes increases oxidant stress and doubles the risk of dying after myocardial infarction, but the mechanisms underlying increased mortality are unknown. Mice with streptozotocin-induced diabetes developed profound heart rate slowing and doubled mortality compared with controls after myocardial infarction. Oxidized Ca(2+)/calmodulin-dependent protein kinase II (ox-CaMKII) was significantly increased in pacemaker tissues from diabetic patients compared with that in nondiabetic patients after myocardial infarction...
March 2013: Journal of Clinical Investigation
Jie He, Xiaoyan Li, Jiqiao Yang, Jichong Huang, Xiaowei Fu, Yonggang Zhang, Hong Fan
BACKGROUND: The M/V polymorphism in the PRNP gene has been extensively examined for the association to the risk of Alzheimer disease (AD); however, results from different studies have been inconsistent. The aim of this study is to evaluate the association between the M/V polymorphism in the PRNP gene and the risk of AD. METHODS: A meta-analysis was carried out to analyze the association between the M/V polymorphism in the PRNP gene and the risk of AD. RESULTS: A total of 4228 cases and 4324 controls in 16 case-control studies were included in the meta-analysis...
March 15, 2013: Journal of the Neurological Sciences
Hai-rong Qian, Lu-ning Wang, Ming-wei Zhu
OBJECTIVE: To examine the relationship between prion protein gene (PRNP) codon 129 polymorphism and Alzheimer's disease (AD) by means of meta-analysis. METHODS: Odds ratios (OR) of prion protein gene codon 129 genotype distribution in AD patients against healthy control was analysed. All the relevant studies were identified and poor-qualified studies were eliminated. A meta-analysis software, Review Manager 4.2 was applied for investigating heterogeneity among individual studies and summarizing effects across studies...
November 2006: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
M T Bishop, P Hart, L Aitchison, H N Baybutt, C Plinston, V Thomson, N L Tuzi, M W Head, J W Ironside, R G Will, J C Manson
BACKGROUND: Identification of possible transmission of variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion has caused concern over spread of the disease within the human population. We aimed to model iatrogenic spread to enable a comparison of transmission efficiencies of vCJD and bovine spongiform encephalopathy (BSE) and an assessment of the effect of the codon-129 polymorphism on human susceptibility. METHODS: Mice were produced to express human or bovine prion protein (PrP) by direct replacement of the mouse PrP gene...
May 2006: Lancet Neurology
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