French Institute of Health and Medical Research

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.

State of the art: using natriuretic peptide levels in clinical practice.

Abstract: Natriuretic peptide (NP) levels (B-type natriuretic peptide (BNP) and N-terminal proBNP) are now widely used in clinical practice and cardiovascular research throughout the world and have been incorporated into most national and international cardiovascular guidelines for heart failure. The role of NP levels in state-of-the-art clinical practice is evolving rapidly. This paper reviews and highlights ten key messages to clinicians: 1) NP levels are quantitative plasma biomarkers of heart failure (HF). 2) NP levels are accurate in the diagnosis of HF. 3) NP levels may help risk stratify emergency department (ED) patients with regard to the need for hospital admission or direct ED discharge. 4) NP levels help improve patient management and reduce total treatment costs in patients with acute dyspnoea. 5) NP levels at the time of admission are powerful predictors of outcome in predicting death and re-hospitalisation in HF patients. 6) NP levels at discharge aid in risk stratification of the HF patient. 7) NP-guided therapy may improve morbidity and/or mortality in chronic HF. 8) The combination of NP levels together with symptoms, signs and weight gain assists in the assessment of clinical decompensation in HF. 9) NP levels can accelerate accurate diagnosis of heart failure presenting in primary care. 10) NP levels may be helpful to screen for asymptomatic left ventricular dysfunction in high-risk patients.

The Biology of Peroxisome Proliferator-Activated Receptors: Relationship With Lipid Metabolism and Insulin Sensitivity

Abstract: Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the superfamily of nuclear receptors. Three isoforms (α, δ, and γ) have been described. They act on DNA response elements as heterodimers with the nuclear retinoic acid receptor. Their natural activating ligands are fatty acids and lipid-derived substrates. PPAR-α is present in liver, heart, and, to a lesser extent, skeletal muscle. When activated, it promotes fatty acid oxidation, ketone body synthesis, and glucose sparing. Fibrates, which are used as hypolipidemic drugs, are ligands of PPAR-α. PPAR-δ is ubiquitous and could also favor fatty acid oxidation in tissues in which PPAR-α is absent or less expressed. PPAR-γ is expressed in adipose tissue, lower intestine, and cells involved in immunity. Activation of PPAR-γ induces the differentiation of preadipocytes into adipocytes and stimulates triglyceride storage. Thiazolidinediones are compounds used as hypoglycemic, muscle insulin-sensitizing agents in type 2 diabetes. Unexpectedly, they are activators of PPAR-γ. Their action on muscle insulin sensitivity may be secondary to the lowering of circulating lipids on PPAR-γ activation and to the secretion by adipocytes of insulin-sensitizing hormones such as adiponectin, all promoting glucose utilization. The PPARs are thus major regulators of lipid and glucose metabolism, allowing adaptation to the prevailing nutritional environment.

Preliminary NINDS neuropathologic criteria for Steele‐Richardson‐Olszewski syndrome (progressive supranuclear palsy)

Abstract: We present the preliminary neuropathologic criteria for progressive supranuclear palsy (PSP) as proposed at a workshop held at the National Institutes of Health, Bethesda, MD, April 24 and 25, 1993. The criteria distinguish typical, atypical, and combined PSP. A semiquantitative distribution of neurofibrillary tangles is the basis for the diagnosis of PSP. A high density of neurofibrillary tangles and neuropil threads in the basal ganglia and brain-stem is crucial for the diagnosis of typical PSP. Tau-positive astrocytes or their processes in areas of involvement help to confirm the diagnosis. Atypical cases of PSP are variants in which the severity or distribution of abnormalities deviates from the typical pattern. Criteria excluding the diagnosis of typical and atypical PSP are large or numerous infarcts, marked diffuse or focal atrophy, Lewy bodies, changes diagnostic of Alzheimer's disease, oligodendroglial argyrophilic inclusions, Pick bodies, diffuse spongiosis, and prion protein-positive amyloid plaques. The diagnosis of combined PSP is proposed when other neurologic disorders exist concomitantly with PSP.

ER–phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells

Abstract: Induction of cytotoxic T-cell immunity requires the phagocytosis of pathogens, virus-infected or dead tumour cells by dendritic cells. Peptides derived from phagocytosed antigens are then presented to CD8+ T lymphocytes on major histocompatibility complex (MHC) class I molecules, a process called "cross-presentation". After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex "loading machinery" (which includes tapasin, calreticulin and Erp57). Here we show that soon after or during formation, phagosomes fuse with the ER. After antigen export to the cytosol and degradation by the proteasome, peptides are translocated by TAP into the lumen of the same phagosomes, before loading on phagosomal MHC class I molecules. Therefore, cross-presentation in dendritic cells occurs in a specialized, self-sufficient, ER-phagosome mix compartment.