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Paris Descartes University

GovernmentParis, France
About: Paris Descartes University is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Transplantation. The organization has 20987 authors who have published 37456 publications receiving 1206222 citations. The organization is also known as: Université Paris V-Descartes & Université de Paris V.


Papers
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Journal ArticleDOI
TL;DR: The tonic current mediated by ambient glutamate in rat hippocampal slices was unaffected when inhibiting vesicular release of transmitters from neurons but was increased upon inhibition of the enzyme converting glutamate in glutamine in glial cells, indicating that ambient glutamate is mainly of glial origin.
Abstract: In several neuronal types of the CNS, glutamate and GABA receptors mediate a persistent current which reflects the presence of a low concentration of transmitters in the extracellular space. Here, we further characterize the tonic current mediated by ambient glutamate in rat hippocampal slices. A tonic current of small amplitude (53.99 +/- 6.48 pA at +40 mV) with the voltage dependency and the pharmacology of NMDA receptors (NMDARs) was detected in virtually all pyramidal cells of the CA1 and subiculum areas. Manipulations aiming at increasing D-serine or glycine extracellular concentrations failed to modify this current indicating that the glycine binding sites of the NMDARs mediating the tonic current were saturated. In contrast, non-transportable inhibitors of glutamate transporters increased the amplitude of this tonic current, indicating that the extracellular concentration of glutamate primarily regulates its magnitude. Neither AMPA/kainate receptors nor metabotropic glutamate receptors contributed significantly to this tonic excitation of pyramidal neurons. In the presence of glutamate transporter inhibitors, however, a significant proportion of the tonic conductance was mediated by AMPA receptors. The tonic current was unaffected when inhibiting vesicular release of transmitters from neurons but was increased upon inhibition of the enzyme converting glutamate in glutamine in glial cells. These observations indicate that ambient glutamate is mainly of glial origin. Finally, experiments with the use-dependent antagonist MK801 indicated that NMDARs mediating the tonic conductance are probably extra-synaptic NMDARs.

214 citations

Journal ArticleDOI
TL;DR: It is crucial to organise national and international registries and collect information prospectively about the natural history of the disease, as AATD is a rare disease and inequalities in access to therapies across Europe should be addressed.
Abstract: α 1 -antitrypsin deficiency (AATD) is the most common hereditary disorder in adults. It is associated with an increased risk of developing pulmonary emphysema and liver disease. The pulmonary emphysema in AATD is strongly linked to smoking, but even a proportion of never-smokers develop progressive lung disease. A large proportion of individuals affected remain undiagnosed and therefore without access to appropriate care and treatment. The most recent international statement on AATD was published by the American Thoracic Society and the European Respiratory Society in 2003. Since then there has been a continuous development of novel, more accurate and less expensive genetic diagnostic methods. Furthermore, new outcome parameters have been developed and validated for use in clinical trials and a new series of observational and randomised clinical trials have provided more evidence concerning the efficacy and safety of augmentation therapy, the only specific treatment available for the pulmonary disease associated with AATD. As AATD is a rare disease, it is crucial to organise national and international registries and collect information prospectively about the natural history of the disease. Management of AATD patients must be supervised by national or regional expert centres and inequalities in access to therapies across Europe should be addressed.

213 citations

Journal ArticleDOI
TL;DR: This position paper provides the first largely shared, interdisciplinary approach for a rational PFO management based on the best available evidence.
Abstract: The presence of a patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions; however, the subject remains controversial and no official statements have been published This interdisciplinary paper, prepared with involvement of eight European scientific societies, aims to review the available trial evidence and to define the principles needed to guide decision making in patients with PFO In order to guarantee a strict process, position statements were developed with the use of a modified grading of recommendations assessment, development, and evaluation (GRADE) methodology A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio The level of evidence and the strength of the position statements of particular management options were weighed and graded according to predefined scales Despite being based often on limited and non-randomised data, while waiting for more conclusive evidence, it was possible to conclude on a number of position statements regarding a rational general approach to PFO management and to specific considerations regarding left circulation thromboembolism For some therapeutic aspects, it was possible to express stricter position statements based on randomised trials This position paper provides the first largely shared, interdisciplinary approach for a rational PFO management based on the best available evidence

213 citations

Journal ArticleDOI
TL;DR: The chemical challenges in generating suitable two-photon probes are discussed, which raises problems in the design of "smart" probes compatible with cell physiology.
Abstract: Molecular systems that can be remotely controlled by light are gaining increasing importance in cell biology, physiology, and neurosciences because of the spatial and temporal precision that is achievable with laser microscopy. Two-photon excitation has significant advantages deep in biological tissues, but raises problems in the design of "smart" probes compatible with cell physiology. This Review discusses the chemical challenges in generating suitable two-photon probes.

213 citations

Journal ArticleDOI
TL;DR: For example, the authors found that three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk, including Cathepsin H (CTSH), Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4), and OX40L.
Abstract: Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip). Three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4, also called OX40L), attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease.

213 citations


Authors

Showing all 21023 results

NameH-indexPapersCitations
Guido Kroemer2361404246571
Cyrus Cooper2041869206782
Jean-Laurent Casanova14484276173
Alain Fischer14377081680
Maxime Dougados134105469979
Carlos López-Otín12649483933
Giuseppe Viale12374072799
Thierry Poynard11966864548
Lorenzo Galluzzi11847771436
Shahrokh F. Shariat118163758900
Richard E. Tremblay11668545844
Olivier Hermine111102643779
Yehezkel Ben-Ari11045944293
Loïc Guillevin10880051085
Gérard Socié10792044186
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20238
202279
20211,082
20201,994
20193,298
20183,323