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81.
Charcot–Marie–Tooth (CMT) neuropathies are inherited neuromuscular disorders caused by a length‐dependent neurodegeneration of peripheral nerves. More than 900 mutations in 60 different genes are causative of the neuropathy. Despite significant progress in therapeutic strategies, the disease remains incurable. The increasing number of genes linked to the disease, and their considerable clinical and genetic heterogeneity render the development of these strategies particularly challenging. In this context, cellular and animals models provide powerful tools. Efficient motor and sensory tests have been developed to assess the behavioral phenotype in transgenic animal models (rodent and fly). When these models reproduce a phenotype comparable to CMT, they allow therapeutic approaches and the discovery of modifiers and biomarkers. In this review, we describe the most convincing transgenic rodent and fly models of CMT and how they can lead to clinical trial. We also discuss the challenges that the research, the clinic, and the pharmaceutical industry will face in developing efficient and accessible treatment for CMT patients. Ann Neurol 2013;74:391–396 相似文献
82.
Benoit Mesnard Maxime Leroy James Hunter Delphine Kervella Marc-Olivier Timsit Lionel Badet Pascal Glemain Emmanuel Morelon Fanny Buron Moglie Le Quintrec-Donnette Vincent Pernin Marc Ladriere Sophie Girerd Christophe Legendre Antoine Sicard Laeticia Albano Stephane De Vergie Clarisse Kerleau Thomas Prudhomme Jérôme Rigaud Diego Cantarovich Gilles Blancho Georges Karam Magali Giral Simon Ville Julien Branchereau For the Données Informatisées et VAlidées en Transplantation/Computerized VAlidated Data in Transplantation Consortium Affiliations† 《BJU international》2022,129(2):225-233
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85.
Boris Gass Emilie Marrer Simona Bara Karine Ligier Florence Molinié Marc Colonna Laetitia Daubisse-Marliac Brigitte Trétarre Bénédicte Lapôtre-Ledoux Anne-Sophie Woronoff Anne-Valérie Guizard Véronique Bouvier Xavier Troussard Christian Gaiddon Delphine Klein Michel Velten Jérémie Jégu 《Annals of epidemiology》2018,28(5):322-327
Purpose
To analyze trends in second primary cancer (SPC) incidence by using a case-mix approach to standardize on first cancer site distribution.Methods
Cases registered by 13 French cancer registries between 1989 and 2010 and followed-up until June 2013 were included. The person-year approach was used to compute standardized incidence ratios (SIRs) of metachronous SPC. Usual SIRs and cancer site–specific weighted SIRs called “case-mix SIRs” (cmSIRs) were estimated by sex and calendar period of first cancer diagnosis. Calendar trends in SIRs and cmSIRs were compared.Results
More than 2.9 million person-years at risk were included. Among males, SIRs dropped from 1.49 to 1.23 between 1989–1994 and 2005–2010, while cmSIRs decreased from 1.40 to 1.27. This difference seems mainly related to a stronger representation of prostate cancers (at lower risk of SPC) and a weaker contribution of bladder and head and neck cancers (at higher risk of SPC) in recent periods of diagnosis. Among females, both SIRs and cmSIRs have remained stable at around 1.22 and 1.21, respectively.Conclusions
The cmSIR is an indicator that is not influenced by changes in first cancer site distribution. Its use should be encouraged to assess second cancer incidence control. 相似文献86.
Heterologous production of albicidin: a promising approach to overproducing and characterizing this potent inhibitor of DNA gyrase 下载免费PDF全文
Vivien E Pitorre D Cociancich S Pieretti I Gabriel DW Rott PC Royer M 《Antimicrobial agents and chemotherapy》2007,51(4):1549-1552
The phytotoxin and polyketide antibiotic albicidin produced by Xanthomonas albilineans is a highly potent DNA gyrase inhibitor. Low yields of albicidin production have slowed studies of its chemical structure. Heterologous expression of albicidin biosynthetic genes in X. axonopodis pv. vesicatoria resulted in a sixfold increase in albicidin production, offering promising strategies for engineering overproduction. 相似文献
87.
Insight into siderophore-carrying peptide biosynthesis: enterobactin is a precursor for microcin E492 posttranslational modification 下载免费PDF全文
Vassiliadis G Peduzzi J Zirah S Thomas X Rebuffat S Destoumieux-Garzón D 《Antimicrobial agents and chemotherapy》2007,51(10):3546-3553
Microcin E492-producing bacteria secrete both unmodified and posttranslationally modified microcins. The modification consists of a C-glucosylated linear trimer of N-(2,3-dihydroxybenzoyl)-l-serine, a catecholate siderophore related to salmochelins and enterobactin. We show here that repression of enterobactin biosynthesis inhibits the acquisition of microcin E492 posttranslational modification, as monitored by high-performance liquid chromatography and mass spectrometry. Furthermore, exogenous enterobactin restored the production of posttranslationally modified microcin in a bacterial strain deficient in enterobactin synthesis. We thus concluded that enterobactin serves as a precursor for the synthesis of the posttranslationally modified microcin and that the unmodified microcin is an incompletely processed form of mature microcin E492. Gene disruption experiments showed that MceC and MceD, two enzymes encoded by the mceABCDEFGHIJ gene cluster, are involved in the synthesis of the microcin E492 posttranslational modification, as followed by mass spectrometry. Genes homologous to iroB and iroD, required for the conversion (linearization and C-glycosylation) of enterobactin into salmochelins, efficiently complemented mceC and mceD, respectively. Based on our results, a model is proposed for the biosynthesis of the mature siderophore-carrying peptide. 相似文献
88.
Six EM Bonhomme D Monteiro M Beldjord K Jurkowska M Cordier-Garcia C Garrigue A Dal Cortivo L Rocha B Fischer A Cavazzana-Calvo M André-Schmutz I 《The Journal of experimental medicine》2007,204(13):3085-3093
Identification of a thymus-seeding progenitor originating from human bone marrow (BM) constitutes a key milestone in understanding the mechanisms of T cell development and provides new potential for correcting T cell deficiencies. We report the characterization of a novel lymphoid-restricted subset, which is part of the lineage-negative CD34+CD10+ progenitor population and which is distinct from B cell–committed precursors (in view of the absence of CD24 expression). We demonstrate that these Lin−CD34+CD10+CD24− progenitors have a very low myeloid potential but can generate B, T, and natural killer lymphocytes and coexpress recombination activating gene 1, terminal deoxynucleotide transferase, PAX5, interleukin 7 receptor α, and CD3ε. These progenitors are present in the cord blood and in the BM but can also be found in the blood throughout life. Moreover, they belong to the most immature thymocyte population. Collectively, these findings unravel the existence of a postnatal lymphoid-polarized population that is capable of migrating from the BM to the thymus. 相似文献
89.
Bordet T Buisson B Michaud M Drouot C Galéa P Delaage P Akentieva NP Evers AS Covey DF Ostuni MA Lacapère JJ Massaad C Schumacher M Steidl EM Maux D Delaage M Henderson CE Pruss RM 《The Journal of pharmacology and experimental therapeutics》2007,322(2):709-720
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive death of cortical and spinal motor neurons, for which there is no effective treatment. Using a cell-based assay for compounds capable of preventing motor neuron cell death in vitro, a collection of approximately 40,000 low-molecular-weight compounds was screened to identify potential small-molecule therapeutics. We report the identification of cholest-4-en-3-one, oxime (TRO19622) as a potential drug candidate for the treatment of ALS. In vitro, TRO19622 promoted motor neuron survival in the absence of trophic support in a dose-dependent manner. In vivo, TRO19622 rescued motor neurons from axotomy-induced cell death in neonatal rats and promoted nerve regeneration following sciatic nerve crush in mice. In SOD1(G93A) transgenic mice, a model of familial ALS, TRO19622 treatment improved motor performance, delayed the onset of the clinical disease, and extended survival. TRO19622 bound directly to two components of the mitochondrial permeability transition pore: the voltage-dependent anion channel and the translocator protein 18 kDa (or peripheral benzodiazepine receptor), suggesting a potential mechanism for its neuroprotective activity. TRO19622 may have therapeutic potential for ALS and other motor neuron and neurodegenerative diseases. 相似文献
90.
No pain scale is available for stroke patients due to the presence of language or cognitive disorders. However, the Faces Pain Scale (FPS), which was initially developed for children, has been used with success in adults with cognitive impairments. The aim of this study is to test whether the FPS could be used in left or right hemispheric stroke patients (LHSP, RHSP). One hundred twenty-seven stoke patients and 21 controls were recruited in 2 rehabilitation units. Construct validity of FPS was assessed by rating and ranking facial expressions. FPS was correlated to a Visual Analog Scale (VAS) and to a Verbal Rating Scale (VRS) for the assessment of shoulder pain. Reliability was determined by test-retest procedures. Performances of RHSP in the ranking and rating procedures were very poor compared to LHSP and to controls. However, in the assessment of patients' shoulder pain, FPS scores were highly correlated with VAS and VRS in both stroke groups (r=0.65-0.82, p<10(-3)). FPS was more reliable in LHSP than in RHSP. It was preferred to VAS and VRS in LHSP, while in RHSP VAS was the preferred scale. The present study provides preliminary support for the validity and the reliability of FPS in LHSP. However, we do not recommend its sole use in stroke patients. Further studies are needed to determine whether FPS can be used in stroke patients for assessing changes in severity of pain over time. 相似文献