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排序方式: 共有365条查询结果,搜索用时 31 毫秒
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El Benna J Hayem G Dang PM Fay M Chollet-Martin S Elbim C Meyer O Gougerot-Pocidalo MA 《Inflammation》2002,26(6):273-278
Superoxide anion (O2°-)production by neutrophil NADPH oxidase participates in arthritic joint lesion formation. Proinflammatory cytokines such as tumor necrosis factor (TNF), interleukin 8 (IL-8) and granulocyte/macrophage-colony stimulating factor (GM-CSF) have a priming effect on neutrophil NADPH oxidase activity. NADPH oxidase activation is dependent on phosphorylation of p47phox, a cytosolic component of the enzyme. We studied O2°-production and p47phox phosphorylation in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and spondylarthropathy (SpA) according to TNF, IL-8 and GM-CSF levels. O2°-production by neutrophils isolated from SF of all the arthritis patients (RA and SpA) was higher than that of circulating resting neutrophils and when stimulated with fMLP or PMA. In addition, p47phox was partially phosphorylated in SF neutrophils compared to circulating neutrophils. High levels of TNF and IL-8 (but not GM-CSF) are detected in patient's SF (compared to circulating blood levels). TNF levels were significantly higher in RA than in SpA SF. These results suggest that increased NADPH oxidase activity could be involved in arthritic joint inflammation through increased p47phox phosphorylation. This could be the result of the presence of high levels of priming agents such as TNF and IL-8 but not GM-CSF. 相似文献
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Frints SG Jun L Fryns JP Devriendt K Teulingkx R Van den Berghe L De Vos B Borghgraef M Chelly J Des Portes V Van Bokhoven H Hamel B Ropers HH Kalscheuer V Raynaud M Moraine C Marynen P Froyen G 《American journal of medical genetics. Part A》2003,(3):367-374
We describe a 59-year-old male (patient A059) with moderate to severe mental retardation (MR) and a pericentric inversion of the X-chromosome: inv(X)(p21.1;q22.1). He had short stature, pectus excavatum, general muscle wasting, and facial dysmorphism. Until now, no other patients with similar clinical features have been described in the literature. Molecular analysis of both breakpoints led to the identification of a novel "Nuclear RNA export factor" (NXF) gene cluster on Xq22.1. Within this cluster, the NXF5 gene was interrupted with subsequent loss of gene expression. Hence, mutation analysis of the NXF5 and its neighboring homologue, the NXF2 gene was performed in 45 men with various forms of syndromic X-linked MR (XLMR) and in 70 patients with nonspecific XLMR. In the NXF5 gene four nucleotide changes: one intronic, two silent, and one missense (K23E), were identified. In the NXF2 gene two changes (one intronic and one silent) were found. Although none of these changes were causative mutations, we propose that NXF5 is a good candidate gene for this syndromic form of XLMR, given the suspected role of NXF proteins is within mRNA export/transport in neurons. Therefore, mutation screening of the NXF gene family in phenotypically identical patients is recommended. 相似文献
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Ravel Jean-Marie Benkirane Mehdi Calmels Nadège Marelli Cecilia Ory-Magne Fabienne Ewenczyk Claire Halleb Yosra Tison François Lecocq Claire Pische Guillaume Casenave Philippe Chaussenot Annabelle Frismand Solène Tyvaert Louise Larrieu Lise Pointaux Morgane Drouot Nathalie Bossenmeyer-Pourié Carine Oussalah Abderrahim Guéant Jean-Louis Leheup Bruno Bonnet Céline Anheim Mathieu Tranchant Christine Lambert Laëtitia Chelly Jamel Koenig Michel Renaud Mathilde 《Journal of neurology》2021,268(5):1927-1937
Journal of Neurology - STUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1... 相似文献
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Arjan PM de Brouwer Sander B Nabuurs Ingrid EC Verhaart Astrid R Oudakker Roel Hordijk Helger G Yntema Jannet M Hordijk-Hos Krysta Voesenek Bert BA de Vries Ton van Essen Wei Chen Hao Hu Jamel Chelly Johan T den Dunnen Vera M Kalscheuer Annemieke M Aartsma-Rus Ben CJ Hamel Hans van Bokhoven Tjitske Kleefstra 《European journal of human genetics : EJHG》2014,22(4):480-485
We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue, Leu3238, in the brain-specific isoform Dp71 of dystrophin. Linkage analysis supported causality as the mutation was present in the 7.6 cM linkage interval on Xp22.11–Xp21.1 with a maximum positive LOD score of 2.41 (MRX85 locus). Molecular modeling predicts that the p.(Leu3238del) deletion results in the destabilization of the C-terminal domain of dystrophin and hence reduces the ability to interact with β-dystroglycan. Correspondingly, Dp71 protein levels in lymphoblastoid cells from the index patient are 6.7-fold lower than those in control cell lines (P=0.08). Subsequent determination of the creatine kinase levels in blood of the index patient showed a mild but significant elevation in serum creatine kinase, which is in line with impaired dystrophin function. In conclusion, we have identified the first DMD mutation in Dp71 that results in ID without muscular dystrophy. 相似文献
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Grenier A Chollet-Martin S Crestani B Delarche C El Benna J Boutten A Andrieu V Durand G Gougerot-Pocidalo MA Aubier M Dehoux M 《Blood》2002,99(8):2997-3004
Hepatocyte growth factor (HGF), a heparin-binding factor, is synthesized as a single-chain inactive precursor (pro-HGF), which is converted by proteolysis to an active heterodimer (mature HGF). HGF has pleiotropic activities and has been implicated in the regulation of mitogenesis, motogenesis, and morphogenesis of epithelial and endothelial cells. As polymorphonuclear neutrophils (PMNs) secrete numerous cytokines involved in the modulation of local inflammation, we investigated their ability to produce HGF. We found that HGF was stored in secretory vesicles and in gelatinase/specific granules. This intracellular stock was rapidly mobilized by degranulation when neutrophils were stimulated with phorbol myristate acetate or N-formylmethionyl-leucyl-phenylalanine. Cycloheximide did not affect the release of HGF. Moreover, HGF messenger RNA and protein expression was found in bone marrow myeloid cells, suggesting that HGF synthesis likely occurs during PMN maturation. In mature circulating PMNs, intracellular HGF was in the pro-HGF form, whereas the HGF secreted by degranulation was the mature form. Furthermore, PMNs pretreated with diisopropyl fluorophosphate only released the pro-HGF form, suggesting that PMN-derived serine protease(s) are involved in the proteolytic process. We also obtained evidence that secreted mature HGF binds PMN-derived glycosaminoglycans (probably heparan sulfate). These findings suggest that PMNs infiltrating damaged tissues may modulate local wound healing and repair through the production of HGF, a major mediator of tissue regeneration. 相似文献