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: It is proposed that SREBP-1c is a major mediator of insulin action on hepatic gene expression and a key regulator of hepatic glucose/lipid metabolism.
Abstract: Hepatic glucokinase plays a key role in glucose metabolism as underlined by the anomalies associated with glucokinase mutations and the consequences of tissue-specific knock-out. In the liver, glucokinase transcription is absolutely dependent on the presence of insulin. The cis-elements and trans-acting factors that mediate the insulin effect are presently unknown; this is also the case for most insulin-responsive genes. We have shown previously that the hepatic expression of the transcription factor sterol regulatory element binding protein-1c (SREBP-1c) is activated by insulin. We show here in primary cultures of hepatocytes that the adenovirus-mediated transduction of a dominant negative form of SREBP-1c inhibits the insulin effect on endogenous glucokinase expression. Conversely, in the absence of insulin, the adenovirus-mediated transduction of a dominant positive form of SREBP-1c overcomes the insulin dependency of glucokinase expression. Hepatic fatty acid synthase and Spot-14 are insulin/glucose-dependent genes. For this latter class of genes, the dominant positive form of SREBP-1c obviates the necessity for the presence of insulin, whereas glucose potentiates the effect of SREBP-1c on their expression. In addition, the insulin dependency of lipid accumulation in cultured hepatocytes is overcome by the dominant positive form of SREBP-1c. We propose that SREBP-1c is a major mediator of insulin action on hepatic gene expression and a key regulator of hepatic glucose/lipid metabolism.
725 citations
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University of Düsseldorf1, VU University Amsterdam2, French Institute of Health and Medical Research3, Mayo Clinic4, University of Amsterdam5, Erasmus University Rotterdam6, University of Newcastle7, Institute of Cancer Research8, Johns Hopkins University9, University of Michigan10, University of New South Wales11
TL;DR: Cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference χ2; 1 df; P = 0.43), and the type or site of STK 11/L KB1 mutation did not significantly influence cancer risk.
Abstract: BACKGROUND: Although an increased cancer risk in Peutz-Jeghers syndrome is established, data on the spectrum of tumors associated with the disease and the influence of germ-line STK11/LKB1 (serine/threonine kinase) mutation status are limited. EXPERIMENTAL DESIGN: We analyzed the incidence of cancer in 419 individuals with Peutz-Jeghers syndrome, and 297 had documented STK11/LKB1 mutations. RESULTS: Ninety-six cancers were found among individuals with Peutz-Jeghers syndrome. The risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 2%, 5%, 17%, 31%, 60%, and 85%, respectively. The most common cancers represented in this analysis were gastrointestinal in origin, gastroesophageal, small bowel, colorectal, and pancreatic, and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 9%, 15%, and 33%, respectively. In women with Peutz-Jeghers syndrome, the risk of breast cancer was substantially increased, being 8% and 31% at ages 40 and 60 years, respectively. Kaplan-Meier analysis showed that cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference chi2 = 0.62; 1 df; P = 0.43). Furthermore, the type or site of STK11/LKB1 mutation did not significantly influence cancer risk. CONCLUSIONS: The results from our study provide quantitative information on the spectrum of cancers and risks of specific cancer types associated with Peutz-Jeghers syndrome.
723 citations
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TL;DR: The sequence of ACE reveals a high degree of internal homology between two large domains, suggesting that the molecule resulted from a gene duplication, and is consistent with the presence of a single gene for ACE in the haploid human genome.
Abstract: The amino-terminal amino acid sequence and several internal peptide sequences of angiotensin I-converting enzyme (ACE; peptidyl-dipeptidase A, kininase II; EC 3.4.15.1) purified from human kidney were used to design oligonucleotide probes. The nucleotide sequence of ACE mRNA was determined by molecular cloning of the DNA complementary to the human vascular endothelial cell ACE mRNA. The complete amino acid sequence deduced from the cDNA contains 1306 residues, beginning with a signal peptide of 29 amino acids. A highly hydrophobic sequence located near the carboxyl-terminal extremity of the molecule most likely constitutes the anchor to the plasma membrane. The sequence of ACE reveals a high degree of internal homology between two large domains, suggesting that the molecule resulted from a gene duplication. Each of these two domains contains short amino acid sequences identical to those located around critical residues of the active site of other metallopeptidases (thermolysin, neutral endopeptidase, and collagenase) and therefore bears a putative active site. Since earlier experiments suggested that a single Zn atom was bound per molecule of ACE, only one of the two domains should be catalytically active. The results of genomic DNA analysis with the cDNA probe are consistent with the presence of a single gene for ACE in the haploid human genome. Whereas the ACE gene is transcribed as a 4.3-kilobase mRNA in vascular endothelial cells, a 3.0-kilobase transcript was detected in the testis, where a shorter form of ACE is synthesized.
723 citations
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TL;DR: It is concluded that learning to read results in the progressive development of an inferotemporal region increasingly responsive to visual words, which is aptly named the visual word form area (VWFA).
723 citations
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TL;DR: Under treatment with alendronate, resorption markers decreased earlier than markers of bone formation, consistent with a direct action of the drug to inhibit osteoclastic bone resor adaptation.
Abstract: To evaluate the clinical utility of recently developed biochemical markers of bone turnover to monitor the response of osteoporotic patients to antiresorptive therapy, we compared the results of three advanced assays for markers of bone resorption and four of bone formation to high pressure liquid chromatography (HPLC)-fluorometric assays for urinary pyridinoline and deoxypyridinoline. These assays were also used to resolve the uncertainties concerning the rate of bone turnover in late postmenopausal (late-PMP) osteoporotic women. The rate of bone turnover in 85 women (mean +/- SD age, 63 +/- 6 yr) with low bone mass and all more than 5 yr postmenopausal (mean +/- SD yr PMP, 16 +/- 7 yr) was compared to that in 46 premenopausal women (mean +/- SD age, 40 +/- 5 yr) randomly selected from a large cohort and all having a normal spine bone mineral density (BMD). The late-PMP osteoporotic patients were a subset of patients enrolled in a double blind, placebo-controlled, randomized study comparing the effects o...
722 citations
Authors
Showing all 109539 results
Name | H-index | Papers | Citations |
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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 |