American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2010
Randomized Controlled TrialAtaluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis.
Nonsense (premature stop codon) mutations in mRNA for the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF) in approximately 10% of patients. Ataluren (PTC124) is an oral drug that permits ribosomes to readthrough premature stop codons in mRNA to produce functional protein. ⋯ In children with nonsense mutation CF, ataluren can induce functional CFTR production and is well tolerated.
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Am. J. Respir. Crit. Care Med. · Nov 2010
Host-derived interleukin-5 promotes adenocarcinoma-induced malignant pleural effusion.
IL-5 is a T helper 2 cytokine important in the trafficking and survival of eosinophils. Because eosinophils can be found in malignant pleural effusions (MPE) from mice and humans, we asked whether IL-5 is involved in the pathogenesis of MPE. ⋯ Host-derived IL-5 promotes experimental MPE and may be involved in the pathogenesis of human MPE.
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Am. J. Respir. Crit. Care Med. · Nov 2010
Chronic intermittent hypoxia alters density of aminergic terminals and receptors in the hypoglossal motor nucleus.
Patients with obstructive sleep apnea (OSA) adapt to the anatomical vulnerability of their upper airway by generating increased activity in upper airway-dilating muscles during wakefulness. Norepinephrine (NE) and serotonin (5-HT) mediate, through α₁-adrenergic and 5-HT₂A receptors, a wake-related excitatory drive to upper airway motoneurons. In patients with OSA, this drive is necessary to maintain their upper airway open. We tested whether chronic intermittent hypoxia (CIH), a major pathogenic factor of OSA, affects aminergic innervation of XII motoneurons that innervate tongue-protruding muscles in a manner that could alter their airway-dilatory action. ⋯ CIH-elicited increase of NE and 5-HT terminal density and increased expression of α₁-adrenoceptors in the XII nucleus may lead to augmentation of endogenous aminergic excitatory drives to XII motoneurons, thereby contributing to the increased upper airway motor tone in patients with OSA.
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Am. J. Respir. Crit. Care Med. · Nov 2010
Apolipoprotein E negatively regulates house dust mite-induced asthma via a low-density lipoprotein receptor-mediated pathway.
Distinct sets of corticosteroid-unresponsive genes modulate disease severity in asthma. ⋯ These findings for the first time identify an apo E-LDLR pathway as an endogenous negative regulator of airway hyperreactivity and goblet cell hyperplasia in asthma. Furthermore, our results demonstrate that strategies that activate the apo E-LDLR pathway, such as apo E mimetic peptides, might be developed into a novel treatment approach for patients with asthma.
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Am. J. Respir. Crit. Care Med. · Nov 2010
Clinical TrialViral load drives disease in humans experimentally infected with respiratory syncytial virus.
Respiratory syncytial virus (RSV) is the leading cause of childhood lower respiratory infection, yet viable therapies are lacking. Two major challenges have stalled antiviral development: ethical difficulties in performing pediatric proof-of-concept studies and the prevailing concept that the disease is immune-mediated rather than being driven by viral load. ⋯ Viral load appears to drive disease manifestations in humans with RSV infection. The observed parallel viral and disease kinetics support a potential clinical benefit of RSV antivirals. This reproducible model facilitates the development of future RSV therapeutics.