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991.
Claire Dossier Nathanael Lapidus Florian Bayer Anne-Laure Sellier-Leclerc Olivia Boyer Loic de Pontual Adrien May Sylvie Nathanson Christine Orzechowski Tabassome Simon Fabrice Carrat Georges Deschênes 《Pediatric nephrology (Berlin, Germany)》2016,31(12):2299-2308
Background
The etiology of idiopathic nephrotic syndrome (INS) remains partially unknown. Viral infections have been reported to be associated with INS onset and relapse. The aim of this study was to describe the epidemiology of a population-based cohort of children with INS and propose a spatiotemporal analysis.Methods
All children aged 6 months to 15 years with INS onset between December 2007 and May 2010 and living in the Paris area were included in a prospective multicenter study. Demographic and clinical features at diagnosis and 2 years were collected.Results
INS was diagnosed in 188 children, 93 % of whom were steroid sensitive. Annual incidence was 3.35/100,000 children. Standardized incidence ratio (SIR) was higher in one of the eight counties: Seine-Saint-Denis, with SIR 1.43 [95 % confidence interval (CI) 1.02–1.95]. A spatial cluster was further identified with higher SIR 1.36 (95 % CI 1.09–1.67). Temporal analysis within this overincidence area showed seasonal variation, with a peak during the winter period (p <0.01). In addition, partition of the Paris area into quintiles of the population showed that the average delay of occurrence, with regard to the first study case, followed a longitudinal progression (p <0.0001).Conclusion
The clustering of cases, the seasonal variation within this particular area, and the progression over the Paris area altogether suggest that INS may occur on an epidemic mode.992.
A nationwide survey was conducted in Switzerland to assess the quality level of osteoporosis management in patients aged 50 years or older presenting with a fragility fracture to the emergency ward of the participating hospitals. Eight centres recruited 4966 consecutive patients who presented with one or more fractures between 2004 and 2006. Of these, 3667 (2797 women, 73.8 years old and 870 men, 73.0 years old in average) were considered as having a fragility fracture and included in the survey. Included patients presented with a fracture of the upper limbs (30.7%), lower limbs (26.4%), axial skeleton (19.5%) or another localisation, including malleolar fractures (23.4%). Thirty-two percent reported one or more previous fractures during adulthood. Of the 2941 (80.2%) hospitalised women and men, only half returned home after discharge. During diagnostic workup, dual x-ray absorptiometry (DXA) measurement was performed in 31.4% of the patients only. Of those 46.0% had a T-score < or =-2.5 SD and 81.1% < or =-1.0 SD. Osteoporosis treatment rate increased from 26.3% before fracture to 46.9% after fracture in women and from 13.0% to 30.3% in men. However, only 24.0% of the women and 13.8% of the men were finally adequately treated with a bone active substance, generally an oral bisphosphonate, with or without calcium / vitamin D supplements. A positive history of previous fracture vs none increased the likelihood of getting treatment with a bone active substance (36.6 vs 17.9%, ? 18.7%, 95% CI 15.1 to 22.3, and 22.6 vs 9.9%, ? 12.7%, CI 7.3 to 18.5, in women and men, respectively). In Switzerland, osteoporosis remains underdiagnosed and undertreated in patients aged 50 years and older presenting with a fragility fracture. 相似文献
993.
Molecularly targeted therapies in adult soft tissue sarcomas: present approach and future directions
BACKGROUND: Sarcomas are rare neoplasms. Given the overwhelming chemotherapy resistance of the disease, patients with progressive and metastatic soft tissue sarcomas are ideal candidates for trials of investigational new drugs. OBJECTIVE: The authors review the molecular mechanisms underlying soft tissue sarcomas and discuss molecularly targeted therapies developed to improve the poor outcome of these uncommon tumors. METHODS: A Medline and American Society of Clinical Oncology abstract search was conducted using the keyword 'soft tissue sarcoma'. Articles and abstracts were reviewed and eligible for inclusion if they used targeted therapies for the treatment of patients with soft tissue sarcomas. Results/conclusion: Phase II clinical trials for patients with soft tissue sarcomas using novel targets and present recognized targets are ongoing and planned. 相似文献
994.
Schreiber O Steinwede K Ding N Srivastava M Maus R Länger F Prokein J Ehlers S Welte T Gunn MD Maus UA 《The Journal of infectious diseases》2008,198(7):1044-1054
995.
Cytoskeleton and apoptosis 总被引:2,自引:0,他引:2
Apoptosis is a genetically programmed and physiological mode of cell death that leads to the removal of unwanted or abnormal cells. Cysteine-proteases called caspases are responsible for the apoptotic execution phase which is characterized by specific biochemical events as well as morphological changes. These changes, which lead to the orderly dismantling of the apoptotic cell, include cell contraction, dynamic membrane blebbing, chromatin condensation, nuclear disintegration, cell fragmentation followed by phagocytosis of the dying cell. They involve major modifications of the cytoskeleton which are largely mediated by cleavage of several of its components by caspases. For example, dynamic membrane blebbing is due to the increased contractility of the acto-myosin system following myosin light chain (MLC) phosphorylation. MLC phosphorylation is a consequence of the cleavage of a Rho GTPase effector, the kinase ROCK I, by caspase-3. This cleavage induces a constitutive kinase activity by removal of an inhibitory domain. Chromatin condensation is facilitated by the processing of lamins by caspases. Collapse of the cytokeratin network is mediated by cleavage of keratin 18. On another hand, the actin cytoskeleton rearrangement needed in the phagocyte for engulfment of the dying cell is due to the activation of the small GTPase Rac, a GTPase of the Rho family that induces actin polymerisation and formation of lamellipodia. In addition to mediating the morphological modifications of the apoptotic cell, several proteins of the cytoskeleton such as actin and keratins are also involved in the regulation of apoptotic signaling. 相似文献
996.
Glutathione: a novel treatment target in psychiatry 总被引:1,自引:0,他引:1
There is accumulating evidence for oxidative stress mechanisms as common pathophysiological pathways in diverse psychiatric disorders, which offers novel treatment targets in oxidation biology systems. Of these the glutathione system has the most favourable theoretical foundation, given its dominance as the most generic of cellular antioxidants. Clinically, this hypothesis has been supported by several recently published studies that have reported on the efficacy of N-acetylcysteine, a glutathione precursor, in the treatment of various psychiatric disorders. This article outlines the multidimensional evidence that currently exists for oxidative stress mechanisms in psychiatric disorders and specifically discusses glutathione as a promising novel therapeutic target. 相似文献
997.
Jorge García‐Piqueras Yolanda García‐Mesa Lucia Crcaba Jorge Feito Isidro Torres‐Parejo Benjamín Martín‐Biedma Juan Cobo Olivia García‐Surez Jose A. Vega 《Journal of anatomy》2019,234(6):839-852
Decline of tactile sensation associated with ageing depends on modifications in skin and both central and peripheral nervous systems. At present, age‐related changes in the periphery of the somatosensory system, particularly concerning the effects on mechanoreceptors, remain unknown. Here we used immunohistochemistry to analyse the age‐dependent changes in Meissner's and Pacinian corpuscles as well as in Merkel cell‐neurite complexes. Moreover, variations in the neurotrophic TrkB‐BDNF system and the mechanoprotein Piezo2 (involved in maintenance of cutaneous mechanoreceptors and light touch, respectively) were evaluated. The number of Meissner's corpuscles and Merkel cells decreased progressively with ageing. Meissner's corpuscles were smaller, rounded in morphology and located deeper in the dermis, and signs of corpuscular denervation were found in the oldest subjects. Pacinian corpuscles generally showed no relevant age‐related alterations. Reduced expression of Piezo2 in the axon of Meissner's corpuscles and in Merkel cells was observed in old subjects, as well was a decline in the BDNF‐TrkB neurotrophic system. This study demonstrates that cutaneous Meissner's corpuscles and Merkel cell‐neurite complexes (and less evidently Pacinian corpuscles) undergo morphological and size changes during the ageing process, as well as a reduction in terms of density. Furthermore, the mechanoprotein Piezo2 and the neurotrophic TrkB‐BDNF system are reduced in aged corpuscles. Taken together, these alterations might explain part of the impairment of the somatosensory system associated with ageing. 相似文献
998.
Stephan C. Collins Ana Uzquiano Mohammed Selloum Olivia Wendling Marion Gaborit Maria Osipenko Marie‐Christine Birling Binnaz Yalcin Fiona Francis 《Journal of anatomy》2019,235(3):637-650
The cerebral cortex is a highly organized structure responsible for advanced cognitive functions. Its development relies on a series of steps including neural progenitor cell proliferation, neuronal migration, axonal outgrowth and brain wiring. Disruption of these steps leads to cortical malformations, often associated with intellectual disability and epilepsy. We have generated a new resource to shed further light on subcortical heterotopia, a malformation characterized by abnormal neuronal position. We describe here the generation and characterization of a knockout (KO) mouse model for Eml1, a microtubule‐associated protein showing mutations in human ribbon‐like subcortical heterotopia. As previously reported for a spontaneous mouse mutant showing a mutation in Eml1, we observe severe cortical heterotopia in the KO. We also observe abnormal progenitor cells in early corticogenesis, likely to be the origin of the defects. EML1 KO mice on the C57BL/6N genetic background also appear to present a wider phenotype than the original mouse mutant, showing additional brain anomalies, such as corpus callosum abnormalities. We compare the anatomy of male and female mice and also study heterozygote animals. This new resource will help unravel roles for Eml1 in brain development and tissue architecture, as well as the mechanisms leading to severe subcortical heterotopia. 相似文献
999.
1000.
Clayton R Ohagen A Goethals O Smets A Van Loock M Michiels L Kennedy-Johnston E Cunningham M Jiang H Bola S Gutshall L Gunn G Del Vecchio A Sarisky R Hallenberger S Hertogs K 《Journal of virological methods》2007,139(1):17-23
The use of targeting moieties is a new and exciting field of scientific research for facilitating the specific delivery of therapeutic agents in HIV-infected patients. The interaction of a potential targeting moiety with its ligand is a crucial factor in the evaluation of a targeted approach for chemotherapeutic intervention. Therefore, we have further characterized the interaction between a potential targeting agent, the monoclonal human antibody F105, and its ligand gp120, a glycoprotein expressed on the surface of HIV-1 infected cells. We demonstrate the specificity of binding and entry of F105 to infected cells. F105 was rapidly taken up into the cell and accumulated in the Golgi apparatus. Kinetic analysis of the F105-gp120 interaction revealed an equilibrium dissociation constant (K(D)) of 0.62 nM, compared with the gp120-CD4 interaction where the K(D) was determined at 35 nM. Consequently, F105 displayed a higher gp120 affinity. This was due to a slower dissociation as compared with the natural ligand. These data further underline the potential of monoclonal antibodies as targeting agents, and offer new insights into the possibility of F105 as a targeting moiety for the delivery of antiretroviral drugs to HIV-1 infected cells. 相似文献