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951.
PY Boelle L Viviani PF Busson H Olesen S Ravilly M Stern B Assael C Barreto P Drevinek M Thomas U Krivec M Mei-Zahav JF Vibert A Clement A Mehta H Corvol 《Orphanet journal of rare diseases》2012,7(1):64
ABSTRACT: BACKGROUND: The clinical course of Cystic Fibrosis (CF) is usually measured using the percent predicted FEV1 and BMI Z-score referenced against a healthy population, since achieving normality is the ultimate goal of CF care. Referencing against age and sex matched CF peers may provide valuable information for patients and for comparison between CF centers or populations. Here, we used a large database of European CF patients to compute CF specific reference equations for FEV1 and BMI, derived CF-specific percentile charts and compared these European data to their nearest international equivalents. METHODS: 34859 FEV1 and 40947 BMI observations were used to compute European CF specific percentiles. Quantile regression was applied to raw measurements as a function of sex, age and height. Results were compared with the North American equivalent for FEV1 and with the WHO 2007 normative values for BMI. RESULTS: FEV1 and BMI percentiles illustrated the large variability between CF patients receiving the best current care. The European CF specific percentiles for FEV1 were significantly different from those in the USA from an earlier era, with higher lung function in Europe. The CF specific percentiles for BMI declined relative to the WHO standard in older children. Lung function and BMI were similar in the two largest contributing European Countries (France and Germany). CONCLUSION: The CF specific percentile approach applied to FEV1 and BMI allows referencing patients with respect to their peers. These data allow peer to peer and population comparisons in CF patients. 相似文献
952.
Thoby-Brisson M Bouvier J Glasco DM Stewart ME Dean C Murdoch JN Champagnat J Fortin G Chandrasekhar A 《PloS one》2012,7(2):e31140
The proper development and maturation of neuronal circuits require precise migration of component neurons from their birthplace (germinal zone) to their final positions. Little is known about the effects of aberrant neuronal position on the functioning of organized neuronal groups, especially in mammals. Here, we investigated the formation and properties of brainstem respiratory neurons in looptail (Lp) mutant mice in which facial motor neurons closely apposed to some respiratory neurons fail to migrate due to loss of function of the Wnt/Planar Cell Polarity (PCP) protein Vangl2. Using calcium imaging and immunostaining on embryonic hindbrain preparations, we found that respiratory neurons constituting the embryonic parafacial oscillator (e-pF) settled at the ventral surface of the medulla in Vangl2Lp/+ and Vangl2Lp/Lp embryos despite the failure of tangential migration of its normally adjacent facial motor nucleus. Anatomically, the e-pF neurons were displaced medially in Lp/+ embryos and rostro-medially Lp/Lp embryos. Pharmacological treatments showed that the e-pF oscillator exhibited characteristic network properties in both Lp/+ and Lp/Lp embryos. Furthermore, using hindbrain slices, we found that the other respiratory oscillator, the preBötzinger complex, was also anatomically and functionally established in Lp mutants. Importantly, the displaced e-pF oscillator established functional connections with the preBötC oscillator in Lp/+ mutants. Our data highlight the robustness of the developmental processes that assemble the neuronal networks mediating an essential physiological function. 相似文献
953.
Sandrine Pelofy Justin Teissié Muriel Golzio Sophie Chabot 《The Journal of membrane biology》2012,245(9):565-571
Despite great potential for disease treatment, small interfering RNA (siRNA) development has been hampered due to its poor stability and the lack of efficient delivery method. To overcome the sensitivity, new generations of chemically modified oligonucleotides have been developed such as the locked nucleic acid (LNA). LNA substitution in an siRNA sequence (siLNA) is supposed to increase its stability and its affinity for its complementary sequence. The purpose of this study was to evaluate the potential benefit of an anti-GFP siLNA using the biophysical delivery method electropermeabilization. We used two types of electrical conditions: electrochemotherapy (ECT), a condition for efficient transfer of small molecules in clinics, and electrogenotherapy (EGT), a condition for efficient transfer of macromolecules. We first confirmed that siLNA was indeed more stable in mouse serum than unmodified siRNA. After determining the ECT and EGT optimal electrical parameters for a human colorectal carcinoma cell line (HCT-116) expressing eGFP, we showed that modifications of siRNA do not interfere with electrotransfer efficiency. However, despite its higher stability and its high electrotransfer efficacy, siLNA was less efficient for eGFP silencing compared to the electrotransferred, unmodified siRNA regardless of the electrical conditions used. Our study highlighted the care that is needed when designing chemically modified oligonucleotides. 相似文献
954.
Albalat-Serradeil M Primazot G Wilhelm D Vallejos JC Vanthuyne N Roussel C 《Amino acids》2012,43(2):687-696
The first successful resolution of rac-α-aminoacetals via diastereoisomeric salt formation with optically pure N-protected aminoacids is reported. The absolute configuration assignment of α-aminoacetal enantiomers is performed by an entirely non-racemizing chemical correlation method involving N-protection and a new efficient hydrolysis step followed by a reduction of the resulting N-protected α-aminoaldehyde intermediates. A racemization method of optically enriched α-aminoacetals is exemplified to allow valorisation of both enantiomers. 相似文献
955.
Hamdan L Bost M Chazot G Bui-Xuan B Vaillant F Dehina L Descotes J Tabib A Mamou Z Timour Q 《Journal of trace elements in medicine and biology》2012,26(2-3):170-173
The involvement of psychotropic drugs in sudden deaths has been highlighted. The objective of this work was to establish a link between selenium levels in heart tissue, psychotropic treatment and sudden death. Selenium levels were measured by electrothermal atomic absorption spectroscopy post-mortem in heart, brain and liver. Histological examination evidenced dilated cardiomyopathy in 45% of cases, left ventricular hypertrophy in 36%, and ischemic coronaropathy in 18%. A significant reduction of myocardial selenium levels compared to controls was seen in patients treated with neuroleptic drugs or meprobamate. No changes in brain or liver selenium levels were seen. These results suggest that selenium deficiency can facilitate sudden death in patients on psychotropic drugs. The reduced activity of glutathione peroxidase due to selenium deficiency can result in augmented oxidative stress in myocardial cells and myocardiopathy leading to sudden death. 相似文献
956.
The wiring of neuronal circuits requires complex mechanisms to guide axon subsets to their specific target with high precision. To overcome the limited number of guidance cues, modulation of axon responsiveness is crucial for specifying accurate trajectories. We report here a novel mechanism by which ligand/receptor co-expression in neurons modulates the integration of other guidance cues by the growth cone. Class 3 semaphorins (Sema3 semaphorins) are chemotropic guidance cues for various neuronal projections, among which are spinal motor axons navigating towards their peripheral target muscles. Intriguingly, Sema3 proteins are dynamically expressed, forming a code in motoneuron subpopulations, whereas their receptors, the neuropilins, are expressed in most of them. Targeted gain- and loss-of-function approaches in the chick neural tube were performed to enable selective manipulation of Sema3C expression in motoneurons. We show that motoneuronal Sema3C regulates the shared Sema3 neuropilin receptors Nrp1 and Nrp2 levels in opposite ways at the growth cone surface. This sets the respective responsiveness to exogenous Nrp1- and Nrp2-dependent Sema3A, Sema3F and Sema3C repellents. Moreover, in vivo analysis revealed a context where this modulation is essential. Motor axons innervating the forelimb muscles are exposed to combined expressions of semaphorins. We show first that the positioning of spinal nerves is highly stereotyped and second that it is compromised by alteration of motoneuronal Sema3C. Thus, the role of the motoneuronal Sema3 code could be to set population-specific axon sensitivity to limb-derived chemotropic Sema3 proteins, therefore specifying stereotyped motor nerve trajectories in their target field. 相似文献
957.
Breathing is a rhythmic motor behavior generated and controlled by hindbrain neuronal networks. Respiratory motor output arises from two distinct, but functionally interacting, rhythmogenic networks: the pre-B?tzinger complex (preB?tC) and the retrotrapezo?d nucleus/parafacial respiratory group (RTN/pFRG). This review outlines recent advances in delineating the genetic specification of the neuronal constituents of these two rhythmogenic networks, their respective roles in respiratory function and how they interact to constitute a functional respiratory circuit ensemble. The often lethal consequences of disruption to these networks found in naturally occurring developmental disorders, transgenic animals, and highly specific lesion studies are described. In addition, we discuss how recent computational models enhance our understanding of how respiratory networks generate and regulate respiratory behavior. 相似文献
958.
959.
There is ample evidence that the presence of tumor-infiltrating T lymphocytes is associated with a favorable prognostic in patients. These observations suggest that a limiting step to immune resistance and immunotherapy could be the capacity of tumor-specific T cells to reach tumor bed. In this article, we review some factors that may influence this infiltration, and in particular the nature of the vasculature, the expression of chemokines or tumor antigens and the presence of dendritic cells and CD4+ T lymphocytes. 相似文献
960.
Miravète M Dissard R Klein J Gonzalez J Caubet C Pecher C Pipy B Bascands JL Mercier-Bonin M Schanstra JP Buffin-Meyer B 《American journal of physiology. Renal physiology》2012,302(11):F1409-F1417
Modified urinary fluid shear stress (FSS) induced by variations of urinary fluid flow and composition is observed in early phases of most kidney diseases. Recently, we reported that renal tubular FSS promotes endothelial cell activation and subsequent adhesion of human monocytes, thereby suggesting that changes in urinary FSS can induce the development of inflammation (Miravète M, Klein J, Besse-Patin A, Gonzalez J, Pecher C, Bascands JL, Mercier-Bonin M, Schanstra JP, Buffin-Meyer B, BBRC 407: 813-817, 2011). Here, we evaluated the influence of tubular FSS on monocytes as they play an important role in the progression of inflammation in nephropathies. Human renal tubular cells (HK-2) were exposed to FSS 0.01 Pa for 30 min or 5 h. Treatment of human THP-1 monocytes with the resulting conditioned medium (FSS-CM) modified the expression of macrophage differentiation markers, suggesting differentiation toward the inflammatory M1-type macrophage. The effect was confirmed in freshly isolated human monocytes. In contrast to endothelial cells, the activation of monocytes by FSS-CM did not require TNF-α. Cytokine array analysis of FSS-CM showed that FSS modified secretion of cytokines by HK-2 cells, particularly by increasing secretion of TGF-β and by decreasing secretion of C-C chemokine ligand 2 (CCL2). Neutralization of TGF-β or CCL2 supplementation attenuated the effect of FSS-CM on macrophage differentiation. Finally, FSS-injured HK-2 cells expressed and secreted early biomarkers of tubular damage such as kidney injury molecule 1 and neutrophil gelatinase-associated lipocalin. In conclusion, changes in urinary FSS should now also be considered as potential insults for tubular cells that initiate/perpetuate interstitial inflammation. 相似文献