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71.
Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases 总被引:5,自引:0,他引:5 下载免费PDF全文
Chamaillard M Philpott D Girardin SE Zouali H Lesage S Chareyre F Bui TH Giovannini M Zaehringer U Penard-Lacronique V Sansonetti PJ Hugot JP Thomas G 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(6):3455-3460
CARD15 is a major susceptibility gene for a frequent multifactorial chronic inflammatory bowel disorder, Crohn disease (CD). By using NF-kappaB activation assays, the cytosolic CARD15 was shown to efficiently detect bacterial peptidoglycan (PGN), reminiscent of the PGN recognition protein surveillance mechanism in Drosophila. The 3 CD-associated variants and 13 additional variants carried by CD patients demonstrated impaired PGN-dependent response revealing null, hypomorphic, or dominant-negative properties. Quantitative parametrization of this response, computed from the patients' CARD15 genotypes, was predictive of several variable CD manifestations. In contrast, CARD15 alleles associated with Blau's syndrome promoted PGN-independent NF-kappaB activation, an observation that accounts for the minimal microbial input in the etiology of this dominant, monogenic inflammatory disorder affecting solely aseptic sites. 相似文献
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Adèle Demain G. W. Max Westby Sara Fernandez-Vidal Carine Karachi Fabrice Bonneville Manh Cuong Do Christine Delmaire Didier Dormont Eric Bardinet Yves Agid Nathalie Chastan Marie-Laure Welter 《Journal of neurology》2014,261(1):196-206
The pathophysiology of gait and balance disorders in elderly people with ‘higher level gait disorders’ (HLGD) is poorly understood. In this study, we aimed to identify the brain networks involved in this disorder. Standardised clinical scores, biomechanical parameters of gait initiation and brain imaging data, including deep white matter lesions (DWML) and brain voxel-based morphometry analyses, were assessed in 20 HLGD patients in comparison to 20 age-matched controls. In comparison to controls, HLGD patients presented a near-normal preparatory phase of gait initiation, but a severe alteration of both locomotor and postural parameters of first-step execution, which was related to ‘axial’ hypokinetic-rigid signs. HLGD patients showed a significant grey matter reduction in the mesencephalic locomotor region (MLR) and the left primary motor cortex. This midbrain atrophy was related to the severity of clinical and neurophysiologically determined balance deficits. HLGD patients also showed a reduction in speed of gait, related to ‘appendicular’ hypokinetic-rigid signs and frontal-lobe-like cognitive deficits. These last two symptoms were correlated with the severity of DWML, found in 12/20 HLGD patients. In conclusion, these data suggest that the gait and balance deficits in HLGD mainly result from the lesion or dysfunction of the network linking the primary motor cortex and the MLR, brain regions known to be involved in the control of gait and balance, whereas cognitive and ‘appendicular’ hypokinetic-rigid signs mainly result from DWML that could be responsible for a dysfunction of the frontal cortico-basal ganglia loops. 相似文献
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Diane Paris MD David Rousset MD Fabrice Bonneville MD PhD Nelly Fabre MD Stanislas Faguer MD PhD Françoise Huguet-Rigal MD Claire Larcher MD Charlotte Martin MD Diane Osinski MD François Gaussiat MD Louis Delamarre MD David Brauge MD Olivier Fourcade MD PhD Thomas Geeraerts MD PhD Ségolène Mrozek MD PhD 《Headache》2020,60(10):2583-2588
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Fabrice Compain Ana Babosan Sylvain Brisse Nathalie Genel Jennifer Audo Florent Ailloud Najiby Kassis-Chikhani Guillaume Arlet Dominique Decré 《Journal of clinical microbiology》2014,52(12):4377-4380
A single multiplex PCR assay targeting seven virulence factors and the wzi gene specific for the K1 and K2 capsular serotypes of Klebsiella pneumoniae was developed and tested on 65 clinical isolates, which included 45 isolates responsible for community-acquired severe human infections. The assay is useful for the surveillance of emerging highly virulent strains. 相似文献