American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jun 2017
Gene Expression Correlated to Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease.
Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. ⋯ In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its phenotypes.
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Am. J. Respir. Crit. Care Med. · Jun 2017
Transmissible Mycobacterium tuberculosis Strains Share Genetic Markers and Immune Phenotypes.
Successful transmission of tuberculosis depends on the interplay of human behavior, host immune responses, and Mycobacterium tuberculosis virulence factors. Previous studies have been focused on identifying host risk factors associated with increased transmission, but the contribution of specific genetic variations in mycobacterial strains themselves are still unknown. ⋯ In this study, we identified genetic markers in convergent evolution of M. tuberculosis toward enhanced transmissibility in vivo that are associated with altered immune responses in vitro.
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Am. J. Respir. Crit. Care Med. · Jun 2017
SOX2 Drives Bronchial Dysplasia in a Novel Organotypic Model of Early Human Squamous Lung Cancer.
Improving the early detection and chemoprevention of lung cancer are key to improving outcomes. The pathobiology of early squamous lung cancer is poorly understood. We have shown that amplification of sex-determining region Y-box 2 (SOX2) is an early and consistent event in the pathogenesis of this disease, but its functional oncogenic potential remains uncertain. We tested the impact of deregulated SOX2 expression in a novel organotypic system that recreates the molecular and microenvironmental context in which squamous carcinogenesis occurs. ⋯ In the appropriate genetic and microenvironmental context, acute deregulation of SOX2 drives bronchial dysplasia. This confirms its oncogenic potential in human cells and affords novel insights into the impact of SOX2 deregulation. This model can be used to test therapeutic agents aimed at chemoprevention.
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Am. J. Respir. Crit. Care Med. · Jun 2017
Gray Matter Hypertrophy and Thickening with Obstructive Sleep Apnea in Middle-aged and Older Adults.
Obstructive sleep apnea causes intermittent hypoxemia, hemodynamic fluctuations, and sleep fragmentation, all of which could damage cerebral gray matter that can be indirectly assessed by neuroimaging. ⋯ Gray matter hypertrophy and thickening were associated with hypoxemia, respiratory disturbances, and sleep fragmentation. These structural changes in a group of middle-aged and older individuals may represent adaptive/reactive brain mechanisms attributed to a presymptomatic stage of obstructive sleep apnea.