scispace - formally typeset
Search or ask a question
Institution

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
More filters
Journal ArticleDOI
TL;DR: In this article, the role of KIF7 in human primary cilia, especially in the Hedgehog pathway through the regulation of GLI targets, and expand the clinical spectrum of ciliopathies.
Abstract: KIF7, the human ortholog of Drosophila Costal2, is a key component of the Hedgehog signaling pathway. Here we report mutations in KIF7 in individuals with hydrolethalus and acrocallosal syndromes, two multiple malformation disorders with overlapping features that include polydactyly, brain abnormalities and cleft palate. Consistent with a role of KIF7 in Hedgehog signaling, we show deregulation of most GLI transcription factor targets and impaired GLI3 processing in tissues from individuals with KIF7 mutations. KIF7 is also a likely contributor of alleles across the ciliopathy spectrum, as sequencing of a diverse cohort identified several missense mutations detrimental to protein function. In addition, in vivo genetic interaction studies indicated that knockdown of KIF7 could exacerbate the phenotype induced by knockdown of other ciliopathy transcripts. Our data show the role of KIF7 in human primary cilia, especially in the Hedgehog pathway through the regulation of GLI targets, and expand the clinical spectrum of ciliopathies.

215 citations

Journal ArticleDOI
TL;DR: The purpose of this review is to describe the most notable advancements in preclinical and clinical research on AAV-based CNS gene therapy and to discuss prospects for future development based on a new generation of vectors and delivery.
Abstract: Gene therapy is at the cusp of a revolution for treating a large spectrum of CNS disorders by providing a durable therapeutic protein via a single administration. Adeno-associated virus (AAV)-mediated gene transfer is of particular interest as a therapeutic tool because of its safety profile and efficiency in transducing a wide range of cell types. The purpose of this review is to describe the most notable advancements in preclinical and clinical research on AAV-based CNS gene therapy and to discuss prospects for future development based on a new generation of vectors and delivery.

215 citations

Journal ArticleDOI
TL;DR: Left lateral section harvesting by laparoscopy is a safe and reproducible procedure, allowing to obtain similar grafts as compared with laparotomy and can therefore be recommended to transplant centers that have previous experience in laparoscopic liver resection.
Abstract: Living donor liver transplantation has become a widely accepted alternative to cadaveric transplantation in children. The use of liver grafts from living donors provides similar or even better short-term graft function and long-term survival rates, especially in children, as compared with whole and split cadaver liver grafts.1,2 The number of children receiving liver grafts from living donors is increasing annually in our institution. This procedure is, however, limited by surgical risks brought upon donors. Left lateral sectionectomy performed through open approach is a well-standardized procedure, associated with a lower rate of complications and mortality than right hepatectomy in living donors for adult transplantation. In living donations for liver transplantation in children, optimizing the postoperative course and limiting abdominal wall injury, especially in those young donors, remain of special concern. Minimally invasive donor nephrectomy using laparoscopic techniques has been widely reported and appeared beneficial for the donor as compared with standard open surgery, decreasing the overall morbidity, and improving donors' quality of life at low cost3–5 without deleterious effects on recipient's long-term kidney function.6 Considering our acquired expertise in laparoscopic liver resection7,8 and our training of standard open surgery as well as liver graft harvesting in living donors, we decided to propose laparoscopic left lateral sectionectomy in donors for liver transplantation in children. Since describing its technical feasibility with the first 2 cases,9 we have developed this procedure and we are now able to assess its safety and reproducibility in our center. Furthermore, during the first period of our experience in graft harvesting for children, a standard open surgical approach was used. This initial experience allowed us to compare both techniques of left lateral section harvesting. The primary goals of the present study were to validate the safety and reproducibility of the laparoscopic technique within our department of surgery.

215 citations

Journal ArticleDOI
TL;DR: New insight is provided into the mechanisms behind BCG’s success in the bladder and it is suggested that parenteral BCG exposure may boost the success rate for bladder cancer treatment, and monitoring patients’ response to purified protein derivative may provide a simple strategy that could improve therapeutic response.
Abstract: Therapeutic intravesical instillation of bacillus Calmette-Guerin (BCG) is effective at triggering inflammation and eliciting successful tumor immunity in patients with non–muscle invasive bladder cancer, with 50 to 70% clinical response. Therapeutic success relies on repeated instillations of live BCG administered as adjuvant therapy shortly after tumor resection; however, the precise mechanisms remain unclear. Using an experimental model, we demonstrate that after a single instillation, BCG coul dd isseminate to bladder draining lymph nodes and prime interferon-g–producing T cells. Nonetheless, repeated instillations with live BCG were necessary for a robust T cell infiltration into the bladder. Parenteral exposure to BCG before instillation overcame this requirement; after the first intravesical instillation, BCG triggered a more robust acute inflammatory process and accelerated T cell entry into the bladder, as compared to the standard protocol. Moreover, parenteral exposure to BCG before intravesical treatment of an orthotopic tumor markedly improved response to therapy. Indeed, patients with sustained preexisting immunity to BCG showed a significant improvement in recurrence-free survival. Together, these data suggest that monitoring patients’ response to purified protein derivative, and, in their absence, boosting BCG responses by parenteral exposure before intravesical treatment initiation, may be a safe and effective means of improving intravesical BCG-induced clinical responses.

214 citations

Journal ArticleDOI
TL;DR: The results suggest that isolated nephronophthisis, Jeune, and Sensenbrenner syndromes are clinically overlapping disorders that can result from a similar molecular cause.
Abstract: A subset of ciliopathies, including Sensenbrenner, Jeune, and short-rib polydactyly syndromes are characterized by skeletal anomalies accompanied by multiorgan defects such as chronic renal failure and retinitis pigmentosa. Through exome sequencing we identified compound heterozygous mutations in WDR19 in a Norwegian family with Sensenbrenner syndrome. In a Dutch family with the clinically overlapping Jeune syndrome, a homozygous missense mutation in the same gene was found. Both families displayed a nephronophthisis-like nephropathy. Independently, we also identified compound heterozygous WDR19 mutations by exome sequencing in a Moroccan family with isolated nephronophthisis. WDR19 encodes IFT144, a member of the intraflagellar transport (IFT) complex A that drives retrograde ciliary transport. We show that IFT144 is absent from the cilia of fibroblasts from one of the Sensenbrenner patients and that ciliary abundance and morphology is perturbed, demonstrating the ciliary pathogenesis. Our results suggest that isolated nephronophthisis, Jeune, and Sensenbrenner syndromes are clinically overlapping disorders that can result from a similar molecular cause.

214 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
Network Information
Related Institutions (5)
French Institute of Health and Medical Research
174.2K papers, 8.3M citations

96% related

University of Paris
174.1K papers, 5M citations

92% related

Erasmus University Rotterdam
91.2K papers, 4.5M citations

91% related

Emory University
122.4K papers, 6M citations

90% related

Université de Montréal
100.4K papers, 4M citations

90% related

Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20238
202279
20211,082
20201,994
20193,298
20183,323