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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: Phaeochromocytoma-paraganglioma syndrome can be diagnosed reliably by an immunohistochemical procedure and SDHB immunohistsochemistry could improve the diagnosis, according to a large retrospective and prospective tumour series.
Abstract: BACKGROUND: Phaeochromocytomas and paragangliomas are neuro-endocrine tumours that occur sporadically and in several hereditary tumour syndromes, including the phaeochromocytoma-paraganglioma syndrome. This syndrome is caused by germline mutations in succinate dehydrogenase B (SDHB), C (SDHC), or D (SDHD) genes. Clinically, the phaeochromocytoma-paraganglioma syndrome is often unrecognised, although 10-30% of apparently sporadic phaeochromocytomas and paragangliomas harbour germline SDH-gene mutations. Despite these figures, the screening of phaeochromocytomas and paragangliomas for mutations in the SDH genes to detect phaeochromocytoma-paraganglioma syndrome is rarely done because of time and financial constraints. We investigated whether SDHB immunohistochemistry could effectively discriminate between SDH-related and non-SDH-related phaeochromocytomas and paragangliomas in large retrospective and prospective tumour series. METHODS: Immunohistochemistry for SDHB was done on 220 tumours. Two retrospective series of 175 phaeochromocytomas and paragangliomas with known germline mutation status for phaeochromocytoma-susceptibility or paraganglioma-susceptibility genes were investigated. Additionally, a prospective series of 45 phaeochromocytomas and paragangliomas was investigated for SDHB immunostaining followed by SDHB, SDHC, and SDHD mutation testing. FINDINGS: SDHB protein expression was absent in all 102 phaeochromocytomas and paragangliomas with an SDHB, SDHC, or SDHD mutation, but was present in all 65 paraganglionic tumours related to multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis type 1. 47 (89%) of the 53 phaeochromocytomas and paragangliomas with no syndromic germline mutation showed SDHB expression. The sensitivity and specificity of the SDHB immunohistochemistry to detect the presence of an SDH mutation in the prospective series were 100% (95% CI 87-100) and 84% (60-97), respectively. INTERPRETATION: Phaeochromocytoma-paraganglioma syndrome can be diagnosed reliably by an immunohistochemical procedure. SDHB, SDHC, and SDHD germline mutation testing is indicated only in patients with SDHB-negative tumours. SDHB immunohistochemistry on phaeochromocytomas and paragangliomas could improve the diagnosis of phaeochromocytoma-paraganglioma syndrome. FUNDING: The Netherlands Organisation for Scientific Research, Dutch Cancer Society, Vanderes Foundation, Association pour la Recherche contre le Cancer, Institut National de la Sante et de la Recherche Medicale, and a PHRC grant COMETE 3 for the COMETE network.

472 citations

Journal ArticleDOI
TL;DR: The intimate connection between autophagy, mitophagy and cardiovascular disorders is discussed and pharmacological or genetic maneuvers that alter the autophagic or mitophagic flux have been shown to influence disease outcome in rodent models of several cardiovascular conditions.
Abstract: Autophagy contributes to the maintenance of intracellular homeostasis in most cells of cardiovascular origin, including cardiomyocytes, endothelial cells, and arterial smooth muscle cells Mitophagy is an autophagic response that specifically targets damaged, and hence potentially cytotoxic, mitochondria As these organelles occupy a critical position in the bioenergetics of the cardiovascular system, mitophagy is particularly important for cardiovascular homeostasis in health and disease Consistent with this notion, genetic defects in autophagy or mitophagy have been shown to exacerbate the propensity of laboratory animals to spontaneously develop cardiodegenerative disorders Moreover, pharmacological or genetic maneuvers that alter the autophagic or mitophagic flux have been shown to influence disease outcome in rodent models of several cardiovascular conditions, such as myocardial infarction, various types of cardiomyopathy, and atherosclerosis In this review, we discuss the intimate connection between autophagy, mitophagy, and cardiovascular disorders

471 citations

Journal ArticleDOI
TL;DR: It is demonstrated that aberrant sensing of nucleic acids can cause immune upregulation and heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (also called MDA5) cause a spectrum of neuroimmunological features consistently associated with an enhanced interferon state.
Abstract: The type I interferon system is integral to human antiviral immunity. However, inappropriate stimulation or defective negative regulation of this system can lead to inflammatory disease. We sought to determine the molecular basis of genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutieres syndrome and of other undefined neurological and immunological phenotypes also demonstrating an upregulated type I interferon response. We found that heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (also called MDA5) cause a spectrum of neuroimmunological features consistently associated with an enhanced interferon state. Cellular and biochemical assays indicate that these mutations confer gain of function such that mutant IFIH1 binds RNA more avidly, leading to increased baseline and ligand-induced interferon signaling. Our results demonstrate that aberrant sensing of nucleic acids can cause immune upregulation.

470 citations

Journal ArticleDOI
TL;DR: The review concludes by stressing the need to improve the understanding of AMT mechanisms at BBB and the effectiveness of cationized proteins and CPP-vectorized proteins as neurotherapeutics.
Abstract: Adsorptive-mediated transcytosis (AMT) provides a means for brain delivery of medicines across the blood-brain barrier (BBB). The BBB is readily equipped for the AMT process: it provides both the potential for binding and uptake of cationic molecules to the luminal surface of endothelial cells, and then for exocytosis at the abluminal surface. The transcytotic pathways present at the BBB and its morphological and enzymatic properties provide the means for movement of the molecules through the endothelial cytoplasm. AMT-based drug delivery to the brain was performed using cationic proteins and cell-penetrating peptides (CPPs). Protein cationization using either synthetic or natural polyamines is discussed and some examples of diamine/polyamine modified proteins that cross BBB are described. Two main families of CPPs belonging to the Tat-derived peptides and Syn-B vectors have been extensively used in CPP vector-mediated strategies allowing delivery of a large variety of small molecules as well as proteins across cell membranes in vitro and the BBB in vivo. CPP strategy suffers from several limitations such as toxicity and immunogenicity—like the cationization strategy—as well as the instability of peptide vectors in biological media. The review concludes by stressing the need to improve the understanding of AMT mechanisms at BBB and the effectiveness of cationized proteins and CPP-vectorized proteins as neurotherapeutics.

470 citations

Journal ArticleDOI
TL;DR: A protocol and a movie describing a straightforward surgical technique, which takes 15–20 min, to consistently remove two-thirds of the liver in mice are provided and it is hoped that it will be widely used and serve to standardize 2/3 PH in mice.
Abstract: The ability of hepatocytes to enter the cell cycle and regenerate the liver after tissue loss provides an in vivo model to study the regulation of proliferation and organ regeneration. The extent of hepatocyte proliferation is directly proportional to the amount of resected liver tissue, and 2/3 partial hepatectomy (2/3 PH) leads to highly synchronized hepatocyte cell-cycle entry and progression. This surgical technique was first described in rats and requires modification for application in mice. Lack of standardization of 2/3 PH in mice has caused discrepancies in the results obtained in different laboratories. Here, we provide a protocol and a movie describing a straightforward surgical technique, which takes 15-20 min, to consistently remove two-thirds of the liver in mice. As this protocol is not associated with mortality and gives highly reproducible results, we hope that it will be widely used and serve to standardize 2/3 PH in mice.

468 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