Institution
French Institute of Health and Medical Research
Government•Paris, France•
About: French Institute of Health and Medical Research is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Receptor. The organization has 109367 authors who have published 174236 publications receiving 8365503 citations.
Topics: Population, Receptor, Immune system, Transplantation, T cell
Papers published on a yearly basis
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TL;DR: In this paper, the authors discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.
Abstract: A dopaminergic deficiency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and akinesia) are associated with a deficiency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine deficiency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic deficit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.
755 citations
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TL;DR: In the largest series of Brugada syndrome patients thus far, event rates in asymptomatic patients were low and gender, familial history of SCD, inducibility of ventricular tachyarrhythmias during electrophysiological study, and the presence of an SCN5A mutation were not predictive of arrhythmic events.
Abstract: BACKGROUND: Brugada syndrome is characterized by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD). Fundamental questions remain on the best strategy for assessing the real disease-associated arrhythmic risk, especially in asymptomatic patients. The aim of the present study was to evaluate the prognosis and risk factors of SCD in Brugada syndrome patients in the FINGER (France, Italy, Netherlands, Germany) Brugada syndrome registry. METHODS AND RESULTS: Patients were recruited in 11 tertiary centers in 4 European countries. Inclusion criteria consisted of a type 1 ECG present either at baseline or after drug challenge, after exclusion of diseases that mimic Brugada syndrome. The registry included 1029 consecutive individuals (745 men; 72%) with a median age of 45 (35 to 55) years. Diagnosis was based on (1) aborted SCD (6%); (2) syncope, otherwise unexplained (30%); and (3) asymptomatic patients (64%). During a median follow-up of 31.9 (14 to 54.4) months, 51 cardiac events (5%) occurred (44 patients experienced appropriate implantable cardioverter-defibrillator shocks, and 7 died suddenly). The cardiac event rate per year was 7.7% in patients with aborted SCD, 1.9% in patients with syncope, and 0.5% in asymptomatic patients. Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events, whereas gender, familial history of SCD, inducibility of ventricular tachyarrhythmias during electrophysiological study, and the presence of an SCN5A mutation were not predictive of arrhythmic events. CONCLUSIONS: In the largest series of Brugada syndrome patients thus far, event rates in asymptomatic patients were low. Inducibility of ventricular tachyarrhythmia and family history of SCD were not predictors of cardiac events.
754 citations
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TL;DR: Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations and further functional analysis of these newly discovered loci will further improve the understanding of glycemic control.
Abstract: Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
753 citations
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TL;DR: Recent discoveries suggest that p21 and p27 might have new activities that are unrelated to their function as CDK inhibitors, which are unexpected functions for these proteins in the control of CDK activation, in the regulation of apoptosis and in transcriptional activation.
753 citations
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Imperial College London1, The Royal Marsden NHS Foundation Trust2, University of Western Australia3, Queensland University of Technology4, St. Vincent's Health System5, University of New South Wales6, Charles University in Prague7, University of Paris8, French Institute of Health and Medical Research9, Max Planck Society10, Ludwig Maximilian University of Munich11, National and Kapodistrian University of Athens12, University of Massachusetts Boston13, University of Hong Kong14, Royal College of Surgeons in Ireland15, University of Palermo16, Kanazawa University17, University of Fukui18, Tokyo Medical and Dental University19, Dokkyo Medical University20, Maastricht University21, Rikshospitalet–Radiumhospitalet22, Tan Tock Seng Hospital23, Autonomous University of Barcelona24, Linköping University25, University of Lausanne26, National Cheng Kung University27, University of Leeds28, University of Edinburgh29, University of Birmingham30, AstraZeneca31, University of Glasgow32, University of Manchester33, Cancer Research UK34, Yale University35, Brown University36, University of Pittsburgh37, Vanderbilt University38, Yeshiva University39, Military Medical Academy40
TL;DR: In this paper, the effect of the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer was investigated using a multivariate analysis.
Abstract: Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras incolorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P=0.004, HR 1.3) and overall survival (P=0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P=0.008, HR 1.5, overall survival P=0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P=0.46, HR 1.12, overall survival P=0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer. ⌐ 2001 Cancer Research Campaign.
753 citations
Authors
Showing all 109539 results
Name | H-index | Papers | Citations |
---|---|---|---|
Guido Kroemer | 236 | 1404 | 246571 |
Pierre Chambon | 211 | 884 | 161565 |
Peer Bork | 206 | 697 | 245427 |
Ronald M. Evans | 199 | 708 | 166722 |
Raymond J. Dolan | 196 | 919 | 138540 |
Matthew Meyerson | 194 | 553 | 243726 |
Charles A. Dinarello | 190 | 1058 | 139668 |
Julie E. Buring | 186 | 950 | 132967 |
Tadamitsu Kishimoto | 181 | 1067 | 130860 |
Didier Raoult | 173 | 3267 | 153016 |
Giuseppe Remuzzi | 172 | 1226 | 160440 |
Zena Werb | 168 | 473 | 122629 |
Nahum Sonenberg | 167 | 647 | 104053 |
Philippe Froguel | 166 | 820 | 118816 |
Gordon J. Freeman | 164 | 579 | 105193 |