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排序方式: 共有3303条查询结果,搜索用时 15 毫秒
41.
Lyra Razanadrakoto Fran?oise Cormier Vanessa Laurienté Elisabetta Dondi Laura Gardano Shulamit Katzav Lionel Guittat Nadine Varin-Blank 《Oncotarget》2015,6(4):2524-2538
Vav family members function as remarkable scaffold proteins that exhibit both GDP/GTP exchange activity for Rho/Rac GTPases and numerous protein-protein interactions via three adaptor Src-homology domains. The exchange activity is under the unique regulation by phosphorylation of tyrosine residues hidden by intra-molecular interactions. Deletion of the autoinhibitory N-terminal region results in an oncogenic protein, onco-Vav, leading to a potent activation of Rac GTPases whereas the proto-oncogene barely leads to transformation. Substitution of conserved residues of the SH2-SH3 adaptor region in onco-Vav reverses oncogenicity. While a unique substitution D797N did not affect transformation induced by onco-Vav, we demonstrate that this single substitution leads to transformation in the Vav1 proto-oncogene highlighting the pivotal role of the adaptor region. Moreover, we identified the cell junction protein β-catenin as a new Vav1 interacting partner. We show that the oncogenicity of activated Vav1 proto-oncogene is associated with a non-degradative phosphorylation of β-catenin at residues important for its functions and its redistribution along the cell membrane in fibroblasts. In addition, a similar interaction is evidenced in epithelial lung cancer cells expressing ectopically Vav1. In these cells, Vav1 is also involved in the modulation of β-catenin phosphorylation. Altogether, our data highlight that only a single mutation in the proto-oncogene Vav1 enhances tumorigenicity. 相似文献
42.
Left superior pulmonary vein connected to superior vena cava vein in a patient with situs inversus totalis: A challenging diagnosis 下载免费PDF全文
Lionel Rozen MD Nadia Debbas MD PhD Nash Damry MD Aurelia David‐Cojocariu MD Didier de Cannière MD PhD Philippe Unger MD PhD 《Echocardiography (Mount Kisco, N.Y.)》2017,34(11):1733-1735
We herein describe the previously unreported combination of partial anomalous venous connection to the superior vena cava combined with situs inversus totalis. Following peripheral contrast injection, bubbles appeared initially in the left atrium allowing the diagnosis of a supra‐atrial connection to be made using transthoracic echocardiography, but this timing was not anymore reproduced during transesophageal echocardiography performed minutes later. Cardiac computed tomography allowed the final diagnosis to be made. This case emphasizes the importance of performing bubble studies both during transesophageal and transthoracic echocardiography. 相似文献
43.
Lucy Mackillop Lise Loerup Katy Bartlett Andrew Farmer Oliver J. Gibson Jane E. Hirst Yvonne Kenworthy Dev A. Kevat Jonathan C. Levy Lionel Tarassenko 《Journal of diabetes science and technology》2014,8(6):1105-1114
Gestational diabetes mellitus (GDM) is defined as new onset or recognition of glucose intolerance in pregnancy. Evidence supports tight blood glucose regulation to prevent adverse maternal and fetal outcomes. Finger-prick blood glucose (BG) testing with frequent clinic review remains the most common method of managing diabetes in pregnancy. The prevalence of GDM is rising globally, pressuring resource-limited services. We have developed an intuitive, interactive, reliable, and accurate management system to record BG measurements and deliver management of GDM remotely. Following an initial scoping phase, a prototype software application was developed using an Android smartphone with BG meter linkage via Bluetooth. A custom website was built for clinician review of the data transmitted by the smartphone. After system refinement, further evaluation was undertaken for usability and reliability in a 48-patient service development project. Women used the system for an average of 13.1 weeks. In all, 19 686 BG measures were transmitted, 98.6% of which had a meal tag. A total of 466 text messages were transmitted. A mean of 30 BG readings per woman per week were transmitted, and 85% of women submitted the minimum requirement of 18 readings per week. We have developed a novel, real-time, smartphone-based BG monitoring management system that allows clinician review of real-time patient-annotated BG results. Results indicate high usage and excellent compliance by women. Robust clinical, economic, and satisfaction evaluations are required. To address these requirements, we are currently conducting a randomized controlled pilot trial. 相似文献
44.
Laetitia Travier Olaya Rendueles Lionel Ferrières Jean-Marie Herry Jean-Marc Ghigo 《Antimicrobial agents and chemotherapy》2013,57(8):3960-3968
Antivirulence strategies targeting bacterial behavior, such as adhesion and biofilm formation, are expected to exert low selective pressure and have been proposed as alternatives to biocidal antibiotic treatments to avoid the rapid occurrence of bacterial resistance. Here, we tested this hypothesis using group 2 capsule polysaccharide (G2cps), a polysaccharidic molecule previously shown to impair bacterium-surface interactions, and we investigated the nature of bacterial resistance to a nonbiocidal antibiofilm strategy. We screened an Escherichia coli mutant library for an increased ability to form biofilm in the presence of G2cps, and we identified several mutants displaying partial but not total resistance to this antibiofilm polysaccharide. Our genetic analysis showed that partial resistance to G2cps results from multiple unrelated mutations leading to modifications in surface physicochemical properties that counteract the changes in ionic charge and Lewis base properties induced by G2cps. Moreover, some of the identified mutants harboring improved biofilm formation in the presence of G2cps were also partially resistant to other antibiofilm molecules. This study therefore shows that alterations of bacterial surface properties mediate only partial resistance to G2cps. It also experimentally validates the potential value of nonbiocidal antibiofilm strategies, since full resistance to antibiofilm compounds is rare and potentially unlikely to arise in clinical settings. 相似文献
45.
Lydia Lacerda Joy McCarthy Shazia F. K. Mungly Edward G. Lynn Michael N. Sack Lionel H. Opie Sandrine Lecour 《Basic research in cardiology》2010,105(6):751-762
Our novel proposal is that TNFα exerts a direct effect on mitochondrial respiratory function in the heart, independently of
its cell surface receptors. TNFα-induced cardioprotection is known to involve reactive oxygen species (ROS) and sphingolipids.
We therefore further propose that this direct mitochondrial effect is mediated via ROS and sphingolipids. The protective concentration
of TNFα (0.5 ng/ml) was added to isolated heart mitochondria from black 6 × 129 mice (WT) and double TNF receptor knockout
mice (TNFR1&2−/−). Respiratory parameters and inner mitochondrial membrane potential were analyzed in the presence/absence of two antioxidants,
N-acetyl-l-cysteine or N-tert-butyl-α-(2-sulfophenyl)nitrone or two antagonists of the sphingolipid pathway, N-oleoylethanolamine (NOE) or imipramine. In WT, TNFα reduced State 3 respiration from 279.3 ± 3 to 119.3 ± 2 (nmol O2/mg protein/min), increased proton leak from 15.7 ± 0.6% (control) to 36.6 ± 4.4%, and decreased membrane potential by 20.5 ± 3.1%
compared to control groups. In TNFR1&2−/− mice, TNFα reduced State 3 respiration from 205.2 ± 4 to 75.7 ± 1 (p < 0.05 vs. respective control). In WT mice, both antioxidants added with TNFα restored State 3 respiration to 269.2 ± 2 and
257.6 ± 2, respectively. Imipramine and NOE also restored State 3 respiration to 248.4 ± 2 and 249.0 ± 2, respectively (p < 0.01 vs. TNFα alone). Similarly, both antioxidant and inhibitors of the sphingolipid pathway restored the proton leak to
pre-TNF values. TNFα-treated mitochondria or isolated cardiac muscle fibers showed an increase in respiration after anoxia–reoxygenation,
but this effect was lost in the presence of an antioxidant or NOE. Similar data were obtained in TNFR1&2−/− mice. TNFα exerts a protective effect on respiratory function in isolated mitochondria subjected to an anoxia–reoxygenation
insult. This effect appears to be independent of its cell surface receptors, but is likely to be mediated by ROS and sphingolipids. 相似文献
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48.
Tracey KAIN Jane ZOCHLING Andrew TAYLOR Nicholas MANOLIOS Malcolm D. SMITH Mark D. REED Matthew A. BROWN Lionel SCHACHNA 《International journal of rheumatic diseases》2008,11(1):45-49
Aim: To develop a set of Australian recommendations for the monitoring and treatment of ankylosing spondylitis (AS) through systematic literature review combined with the opinion of practicing rheumatologists. Methods: A set of eight questions, four in each domain of monitoring and treatment, were formulated by voting and the Delphi method. The results of a systematic literature review addressing each question were presented to the 23 participants of the Australian 3E meeting. All participants were clinical rheumatologists experienced in the daily management of AS. Results: After three rounds of breakout sessions to discuss the findings of the literature review, a set of recommendations was finalized after discussion and voting. The category of evidence and strength of recommendation were determined for each proposal. The level of agreement among participants was excellent (mean 84%, range 64–100%). Conclusions: The 12 recommendations developed from evidence and expert opinion provide guidance for the daily management of AS patients. For most recommendations, we found a paucity of supportive evidence in the literature highlighting the need for additional clinical studies. 相似文献
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50.
Nihar R. Desai Rolin L. Wade Pin Xiang Lionel Pinto Sasikiran Nunna Xin Wang Jason Exter Katherine E. Mues Mohdhar Habib ChiChang Chen 《Clinical cardiology》2021,44(5):715
BackgroundLow‐density lipoprotein cholesterol (LDL‐C) is a risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited real‐world data on LDL‐C lowering with evolocumab in United States clinical practice.HypothesisWe assessed LDL‐C lowering during 1 year of evolocumab therapy.MethodsThis retrospective cohort study used linked laboratory (Prognos) and medical claims (IQVIA Dx/LRx and PharMetrics Plus®) data. Patients with a first fill for evolocumab between 7/1/2015 and 10/31/2019 (index event) and LDL‐C ≥ 70 mg/dL were included (overall cohort; N = 5897). Additionally, a patient subgroup with a recent myocardial infarction (MI) within 12 months (median 130 days) before the first evolocumab fill was identified (N = 152). Reduction from baseline LDL‐C was calculated based on the lowest LDL‐C value recorded during a 12‐month follow‐up period.ResultsThe mean (SD) age was 65 (10) years; 61.9% of patients had ASCVD diagnoses and 70.7% of patients were in receipt of lipid‐lowering therapy. Following evolocumab treatment, changes in LDL‐C from baseline were −60% in the overall cohort (median [interquartile range (IQR)] 146 [115–180] mg/dL to 58 [36–84] mg/dL) and −65% in the recent MI subgroup (median [IQR] 137 [109–165] mg/dL to 48 [30–78] mg/dL). In the overall cohort and recent MI subgroup, 62.1% and 69.7% of patients achieved LDL‐C < 70 mg/dL, respectively.ConclusionsIn this real‐world analysis, evolocumab was associated with significant reductions in LDL‐C comparable to that seen in the FOURIER clinical trial, which were durable over 1 year of treatment. 相似文献