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.

Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea

Abstract: Acne rosacea is an inflammatory skin disease that affects 3% of the US population over 30 years of age and is characterized by erythema, papulopustules and telangiectasia. The etiology of this disorder is unknown, although symptoms are exacerbated by factors that trigger innate immune responses, such as the release of cathelicidin antimicrobial peptides. Here we show that individuals with rosacea express abnormally high levels of cathelicidin in their facial skin and that the proteolytically processed forms of cathelicidin peptides found in rosacea are different from those present in normal individuals. These cathelicidin peptides are a result of a post-translational processing abnormality associated with an increase in stratum corneum tryptic enzyme (SCTE) in the epidermis. In mice, injection of the cathelicidin peptides found in rosacea, addition of SCTE, and increasing protease activity by targeted deletion of the serine protease inhibitor gene Spink5 each increases inflammation in mouse skin. The role of cathelicidin in enabling SCTE-mediated inflammation is verified in mice with a targeted deletion of Camp, the gene encoding cathelicidin. These findings confirm the role of cathelicidin in skin inflammatory responses and suggest an explanation for the pathogenesis of rosacea by demonstrating that an exacerbated innate immune response can reproduce elements of this disease.

Chronic Infantile Neurological Cutaneous and Articular Syndrome Is Caused by Mutations in CIAS1, a Gene Highly Expressed in Polymorphonuclear Cells and Chondrocytes

Abstract: Chronic infantile neurological cutaneous and articular (CINCA) syndrome is a severe chronic inflammatory disease of early onset, characterized by cutaneous symptoms, central-nervous-system involvement, and arthropathy. In the present study, we report, in seven unrelated patients with CINCA syndrome, distinct missense mutations within the nucleotide-binding site of CIAS1, a gene encoding cryopyrin and previously shown to cause Muckle-Wells syndrome and familial cold urticaria. Because of the severe cartilage overgrowth observed in some patients with CINCA syndrome and the implications of polymorphonuclear cell infiltration in the cutaneous and neurological manifestations of this syndrome, the tissue-specific expression of CIAS1 was evaluated. A high level of expression of CIAS1 was found to be restricted to polymorphonuclear cells and chondrocytes. These findings demonstrate that CIAS1 missense mutations can result in distinct phenotypes with only a few overlapping symptoms and suggest that this gene may function as a potential inducer of apoptosis.

Primary Hepatocytes: Current Understanding of the Regulation of Metabolic Enzymes and Transporter Proteins, and Pharmaceutical Practice for the Use of Hepatocytes in Metabolism, Enzyme Induction, Transporter, Clearance, and Hepatotoxicity Studies

Abstract: This review brings you up-to-date with the hepatocyte research on: 1) in vitro-in vivo correlations of metabolism and clearance; 2) CYP enzyme induction, regulation, and cross-talk using human hepatocytes and hepatocyte-like cell lines; 3) the function and regulation of hepatic transporters and models used to elucidate their role in drug clearance; 4) mechanisms and examples of idiosyncratic and intrinsic hepatotoxicity; and 5) alternative cell systems to primary human hepatocytes. We also report pharmaceutical perspectives of these topics and compare methods and interpretations for the drug development process.

Quantitative assessment of breast lesion viscoelasticity: initial clinical results using supersonic shear imaging.

Abstract: This paper presents an initial clinical evaluation of in vivo elastography for breast lesion imaging using the concept of supersonic shear imaging. This technique is based on the combination of a radiation force induced in tissue by an ultrasonic beam and an ultrafast imaging sequence capable of catching in real time the propagation of the resulting shear waves. The local shear wave velocity is recovered using a time-offlight technique and enables the 2-D mapping of shear elasticity. This imaging modality is implemented on a conventional linear probe driven by a dedicated ultrafast echographic device. Consequently, it can be performed during a standard echographic examination. The clinical investigation was performed on 15 patients, which corresponded to 15 lesions (4 cases BI-RADS 3, 7 cases BI-RADS 4 and 4 cases BI-RADS 5). The ability of the supersonic shear imaging technique to provide a quantitative and local estimation of the shear modulus of abnormalities with a millimetric resolution is illustrated on several malignant (invasive ductal and lobular carcinoma) and benign cases (fibrocystic changes and viscous cysts). In the investigated cases, malignant lesions were found to be significantly different from benign solid lesions with respect to their elasticity values. Cystic lesions have shown no shear wave propagate at all in the lesion (because shear waves do not propage in liquid). These preliminary clinical results directly demonstrate the clinical feasibility of this new elastography technique in providing quantitative assessment of relative stiffness of breast tissues. This technique of evaluating tissue elasticity gives valuable information that is complementary to the B-mode morphologic information. More extensive studies are necessary to validate the assumption that this new mode potentially helps the physician in both false-positive and false-negative rejection.

Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells

Abstract: The growth and repair of skeletal muscle after birth depends on satellite cells that are characterized by the expression of Pax7. We show that Pax3, the paralogue of Pax7, is also present in both quiescent and activated satellite cells in many skeletal muscles. Dominant-negative forms of both Pax3 and -7 repress MyoD, but do not interfere with the expression of the other myogenic determination factor, Myf5, which, together with Pax3/7, regulates the myogenic differentiation of these cells. In Pax7 mutants, satellite cells are progressively lost in both Pax3-expressing and -nonexpressing muscles. We show that this is caused by satellite cell death, with effects on the cell cycle. Manipulation of the dominant-negative forms of these factors in satellite cell cultures demonstrates that Pax3 cannot replace the antiapoptotic function of Pax7. These findings underline the importance of cell survival in controlling the stem cell populations of adult tissues and demonstrate a role for upstream factors in this context.