tailieunhanh - Báo cáo y học: " Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài:" Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect. | Peca et al. Respiratory Research 2011 12 115 http content 12 1 115 RESPIRATORY RESEARCH RESEARCH Open Access Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect 12 3 4 13 Donatella Peca Stefania Petrini Chryssoula Tzialla Renata Boldrini Francesco Morini Mauro Stronati Virgilio P Carnielli5 Paola E Cogo6 and Olivier Danhaive1 Abstract Background Mutations of genes affecting surfactant homeostasis such as SFTPB SFTPC and ABCA3 lead to diffuse lung disease in neonates and children. Haploinsufficiency of the gene encoding the thyroid transcription factor-1 TTF-1 - critical for lung thyroid and central nervous system morphogenesis and function - causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored. We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant. Methods The subject was an infant with severe neonatal respiratory distress syndrome followed by recurrent respiratory failure episodes hypopituitarism and neurological abnormalities. Lung histology and ultrastructure were assessed by surgical biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing and array chromatine genomic hybridization aCGH . Surfactant protein expression in lung tissue was analyzed by confocal immunofluorescence microscopy. For kinetics studies surfactant protein B and disaturated phosphatidylcholine DSPC were isolated from serial tracheal aspirates after intravenous administration of stable isotope-labeled 2H2O and 13C-leucine fractional synthetic rate was derived from gas chromatography mass spectrometry 2H and 13C enrichment curves. Six intubated infants with no primary lung disease were used as controls. Results Lung biopsy showed desquamative interstitial pneumonitis and lamellar body abnormalities suggestive of .