作者
André Kübler, Brian Luna, Christer Larsson, Nicole C Ammerman, Bruno B Andrade, Marlene Orandle, Kevin W Bock, Ziyue Xu, Ulas Bagci, Daniel J Mollura, John Marshall, Jay Burns, Kathryn Winglee, Bintou Ahmadou Ahidjo, Laurene S Cheung, Mariah Klunk, Sanjay K Jain, Nathella Pavan Kumar, Subash Babu, Alan Sher, Jon S Friedland, Paul TG Elkington, William R Bishai
发表日期
2015/2
期刊
The Journal of pathology
卷号
235
期号
3
页码范围
431-444
出版商
John Wiley & Sons, Ltd
简介
Active tuberculosis (TB) often presents with advanced pulmonary disease, including irreversible lung damage and cavities. Cavitary pathology contributes to antibiotic failure, transmission, morbidity and mortality. Matrix metalloproteinases (MMPs), in particular MMP‐1, are implicated in TB pathogenesis. We explored the mechanisms relating MMP/TIMP imbalance to cavity formation in a modified rabbit model of cavitary TB. Our model resulted in consistent progression of consolidation to human‐like cavities (100% by day 28), with resultant bacillary burdens (>107 CFU/g) far greater than those found in matched granulomatous tissue (105 CFU/g). Using a novel, breath‐hold computed tomography (CT) scanning and image analysis protocol, we showed that cavities developed rapidly from areas of densely consolidated tissue. Radiological change correlated with a decrease in functional lung tissue, as estimated by …
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