scispace - formally typeset
Search or ask a question
Institution

University of Paris

EducationParis, France
About: University of Paris is a education organization based out in Paris, France. It is known for research contribution in the topics: Population & Transplantation. The organization has 102426 authors who have published 174180 publications receiving 5041753 citations. The organization is also known as: Sorbonne.


Papers
More filters
Journal ArticleDOI
TL;DR: The assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation, and the concept of de‐escalation of therapy is introduced in the treatment assessment scheme.
Abstract: This Executive Summary of the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 Report focuses primarily on the revised and novel parts of the document. The most significant changes include: (i) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; (ii) for each of the groups A to D, escalation strategies for pharmacological treatments are proposed; (iii) the concept of de-escalation of therapy is introduced in the treatment assessment scheme; (iv)non-pharmacological therapies are comprehensively presented and (v) the importance of co-morbid conditions in managing COPD is reviewed.

683 citations

Journal ArticleDOI
TL;DR: PML is identified as the first protein degraded by SUMO-dependent polyubiquitination, as it recruits not only RNF4, ubiquitin and proteasomes, but also many SUMOylated proteins onto PML nuclear bodies, which could physically integrate thesumOylation, ubiquItination and degradation pathways.
Abstract: In acute promyelocytic leukaemia (APL), arsenic trioxide induces degradation of the fusion protein encoded by the PML-RARA oncogene, differentiation of leukaemic cells and produces clinical remissions. SUMOylation of its PML moiety was previously implicated, but the nature of the degradation pathway involved and the role of PML-RARalpha catabolism in the response to therapy have both remained elusive. Here, we demonstrate that arsenic-induced PML SUMOylation triggers its Lys 48-linked polyubiquitination and proteasome-dependent degradation. When exposed to arsenic, SUMOylated PML recruits RNF4, the human orthologue of the yeast SUMO-dependent E3 ubiquitin-ligase, as well as ubiquitin and proteasomes onto PML nuclear bodies. Arsenic-induced differentiation is impaired in cells transformed by a non-degradable PML-RARalpha SUMOylation mutant or in APL cells transduced with a dominant-negative RNF4, directly implicating PML-RARalpha catabolism in the therapeutic response. We thus identify PML as the first protein degraded by SUMO-dependent polyubiquitination. As PML SUMOylation recruits not only RNF4, ubiquitin and proteasomes, but also many SUMOylated proteins onto PML nuclear bodies, these domains could physically integrate the SUMOylation, ubiquitination and degradation pathways.

680 citations

Journal ArticleDOI
TL;DR: Early blockade of the renin-angiotensin system in patients with type 1 diabetes did not slow nephropathy progression but slowed the progression of retinopathy.
Abstract: Background Nephropathy and retinopathy remain important complications of type 1 diabetes. It is unclear whether their progression is slowed by early administration of drugs that block the renin–angiotensin system. Methods We conducted a multicenter, controlled trial involving 285 normotensive patients with type 1 diabetes and normoalbuminuria and who were randomly assigned to receive losartan (100 mg daily), enalapril (20 mg daily), or placebo and followed for 5 years. The primary end point was a change in the fraction of glomerular volume occupied by mesangium in kidney-biopsy specimens. The retinopathy end point was a progression on a retinopathy severity scale of two steps or more. Intention-to-treat analysis was performed with the use of linear regression and logistic-regression models. Results A total of 90% and 82% of patients had complete renal-biopsy and retinopathy data, respectively. Change in mesangial fractional volume per glomerulus over the 5-year period did not differ significantly between the placebo group (0.016 units) and the enalapril group (0.005, P = 0.38) or the losartan group (0.026, P = 0.26), nor were there significant treatment benefits for other biopsy-assessed renal structural variables. The 5-year cumulative incidence of microalbuminuria was 6% in the placebo group; the incidence was higher with losartan (17%, P = 0.01 by the log-rank test) but not with enalapril (4%, P = 0.96 by the log-rank test). As compared with placebo, the odds of retinopathy progression by two steps or more was reduced by 65% with enalapril (odds ratio, 0.35; 95% confidence interval [CI], 0.14 to 0.85) and by 70% with losartan (odds ratio, 0.30; 95% CI, 0.12 to 0.73), independently of changes in blood pressure. There were three biopsy-related serious adverse events that completely resolved. Chronic cough occurred in 12 patients receiving enalapril, 6 receiving losartan, and 4 receiving placebo. Conclusions Early blockade of the renin–angiotensin system in patients with type 1 diabetes did not slow nephropathy progression but slowed the progression of retinopathy. (ClinicalTrials.gov number, NCT00143949.)

680 citations

Journal ArticleDOI
TL;DR: In HIV-infected patients with limited treatment options, raltegravir plus optimization background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks.
Abstract: Results In the combined studies, 699 of 703 randomized patients (462 and 237 in the raltegravir and placebo groups, respectively) received the study drug. Seventeen of the 699 patients (2.4%) discontinued the study before week 16. Discontinuation was related to the study treatment in 13 of these 17 patients: 7 of the 462 raltegravir recipients (1.5%) and 6 of the 237 placebo recipients (2.5%). The results of the two studies were consistent. At week 16, counting noncompletion as treatment failure, 355 of 458 raltegravir recipients (77.5%) had HIV-1 RNA levels below 400 copies per milliliter, as compared with 99 of 236 placebo recipients (41.9%, P<0.001). Suppression of HIV-1 RNA to a level below 50 copies per milliliter was achieved at week 16 in 61.8% of the raltegravir recipients, as compared with 34.7% of placebo recipients, and at week 48 in 62.1% as compared with 32.9% (P<0.001 for both comparisons). Without adjustment for the length of follow-up, cancers were detect ed in 3.5% of raltegravir recipients and in 1.7% of placebo recipients. The overall frequencies of drug-related adverse events were similar in the raltegravir and placebo groups. Conclusions In HIV-infected patients with limited treatment options, raltegravir plus optimized background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks. (ClinicalTrials.gov numbers, NCT00293267 and NCT00293254.)

680 citations

Journal ArticleDOI
TL;DR: In this article, uniform estimates and blow-up behavior for solutions of −δ(u) = v(x)eu in two dimensions are presented, with a focus on partial differential equations.
Abstract: (1991). Uniform estimates and blow–up behavior for solutions of −δ(u)=v(x)eu in two dimensions. Communications in Partial Differential Equations: Vol. 16, No. 8-9, pp. 1223-1253.

679 citations


Authors

Showing all 102613 results

NameH-indexPapersCitations
Guido Kroemer2361404246571
David H. Weinberg183700171424
Paul M. Thompson1832271146736
Chris Sander178713233287
Sophie Henrot-Versille171957157040
Richard H. Friend1691182140032
George P. Chrousos1691612120752
Mika Kivimäki1661515141468
Martin Karplus163831138492
William J. Sandborn1621317108564
Darien Wood1602174136596
Monique M.B. Breteler15954693762
Paul Emery1581314121293
Wolfgang Wagner1562342123391
Joao Seixas1531538115070
Network Information
Related Institutions (5)
Centre national de la recherche scientifique
382.4K papers, 13.6M citations

95% related

École Normale Supérieure
99.4K papers, 3M citations

94% related

Imperial College London
209.1K papers, 9.3M citations

93% related

Sapienza University of Rome
155.4K papers, 4.3M citations

93% related

University of Groningen
69.1K papers, 2.9M citations

93% related

Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202376
2022602
202116,433
202015,008
201911,047
20189,090