Effective inhibition of p53 activity with PFT in rat lungs.

<p>Effect of chronic PFT treatment on p53, p21 and Bax protein levels in rat lungs (5 animals per group). A: Representative western immunoblots of p53 (53 kDa), p21 (21 kDa), Bax (23 kDa) and βactin (42 kDa) protein levels in rat lungs. B-D: Quantification of p53, p21 and Bax western blots. Values represent mean ± SEM of the protein level / actin level quantification (n = 5). ** p<0.01 vs. Control group (Mann-Whitney tests).</p

Pro-proliferative and anti-apoptotic effects of PFT in human control PA-SMCs.

<p>A: Growth of PA-SMCs in response to increasing doses of PFT (1, 10, 50 μM), evaluated by MTT assays. Values are means ± SEM of 4 experiments. *** p<0.001 vs. corresponding Base (Dunnett post-tests). B: Illustrations of the morphological protective effect of increasing doses of PFT (1 μM: image C, 10 μM: image D, 50 μM: image E) against cellular death induced by etoposide (image B). Image A = non treated condition. Scale bar: 37,5 μm. C: Effect of PFT treatment (50 μM) on PA-SMCs apoptosis induced by H2O2 (150 μM) evaluated by TUNEL assays. The ratio of TUNEL positives cells / total cells was calculated on each picture (24 pictures (from 6 different patients) in basal condition and 16 pictures (from 4 different patients) in H₂O₂ condition) and values are means ± SEM (expressed in percentages).** p<0.01; *** p<0.001; ****p<0.0001 (unpaired t-tests). D: Representative images of apoptosis assays with red TUNEL staining and blue DAPI staining. Images A and C illustrate the solvent conditions, respectively without and with 150 μM H202 treatment. Images B and D illustrate the 50 μM PFT conditions, respectively without and with 150 μM H202 treatment. Scale bars: 50 μm.</p

Expression of p53 and its targets in rat lungs during the development of MCT-PH.

<p>Lungs were removed at day 1, day 3, day 7, day 14 and day 21 after the monocrotaline injection (day 0) (5 animals per group). A: Representative western immunoblots of p53 (55 kDa), p21 (21 kDa), Bax (21 kDa), MDM2 (90 kDa) and βactin (42 kDa) protein levels in rat lungs. B-E: Quantification of p53, p21, Bax and MDM2 protein levels from western blots analysis. Values represent mean ± SEM of the protein level / actin level quantification (n = 5). * p<0.05; ** p<0.01 vs. Control group (Mann-Whitney tests).</p

Clinical and Molecular Genetic Features of Pulmonary Hypertension in Patients with Hereditary Hemorrhagic Telangiectasia

Background Most patients with familial primary pulmonary hypertension have defects in the gene for bone morphogenetic protein receptor II (BMPR2), a member of the transforming growth factor b (TGF-b) superfamily of receptors. Because patients with hereditary hemorrhagic telangiectasia may have lung disease that is indistinguishable from primary pulmonary hypertension, we investigated the genetic basis of lung disease in these patients. Methods We evaluated members of five kindreds plus one individual patient with hereditary hemorrhagic telangiectasia and identified 10 cases of pulmonary hypertension. In the two largest families, we used microsatellite markers to test for linkage to genes encoding TGF-b–receptor proteins, including endoglin and activin-receptor–like kinase 1 (ALK1), and BMPR2. In subjects with hereditary hemorrhagic telangiectasia and pulmonary hypertension, we also scanned ALK1 and BMPR2 for mutations. Results We identified suggestive linkage of pulmonary hypertension with hereditary hemorrhagic telangiectasia on chromosome 12q13, a region that includes ALK1. We identified amino acid changes in activinreceptor–like kinase 1 that were inherited in subjects who had a disorder with clinical and histologic features indistinguishable from those of primary pulmonary hypertension. Immunohistochemical analysis in four subjects and one control showed pulmonary vascular endothelial expression of activin-receptor–like kinase 1 in normal and diseased pulmonary arteries. Conclusions Pulmonary hypertension in association with hereditary hemorrhagic telangiectasia can involve mutations in ALK1. These mutations are associated with diverse effects, including the vascular dilatation characteristic of hereditary hemorrhagic telangiectasia and the occlusion of small pulmonary arteries that is typical of primary pulmonary hypertension. (N Engl J Med 2001;345:325-34.

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle.

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease