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Philip Morris Records; bibliography; budget; budget review; form; research proposal, scientific; extr, extra; marg, marginalia

Philip Morris Records; bibliography; budget; budget review; form; research proposal, scientific; extr, extra; marg, marginalia

Philip Morris Records; bibliography; budget; budget review; form; research proposal, scientific; extr, extra; marg, marginalia

Philip Morris Records; report, scientific; extr, extra

This article is from PLoS ONE , volume 9 . Abstract Background: Hyperresponsiveness to inhaled non-infectious microbial particles (NIMPs) has been associated with illnesses in the airways. Hypersensitivity pneumonitis (HP) is considered to be the prototype for these NIMPs-related diseases; however, there is no consensus on the definitions or diagnostic criteria for HP and the spectrum of related illnesses. Methods and Findings: In order to identify the possible diagnostic markers for illnesses associated with NIMPs in alveolar lining fluid, we performed a proteomic analysis using a two-dimensional difference gel electrophoresis on bronchoalveolar lavage (BAL) fluid from patients with exposure to NIMPs in the context of damp building-related illness (DBRI) or conditions on the borderline to acute HP, designated here as agricultural type of microbial exposure (AME). Samples from patients with HP and sarcoidosis (SARC) were included for reference. Results were compared to results of healthy subjects (CTR). Western blot was used for validation of potential marker proteins from BAL fluid and plasma. Protein expression patterns suggest a close similarity between AME and HP, while DBRI was similar to CTR. However, in DBRI the levels of the inflammation associated molecules galectin-3 and alpha-1-antitrypsin were increased. A novel finding emerging from this study was the increases of semenogelin levels in BAL fluid from patients with AME, HP and SARC. Histone 4 levels were increased in AME, HP and SARC. Elevated plasma levels of histone 2B were detected in HP and SARC, suggesting it to be a potential blood indicator for inflammatory diseases of the lungs. Conclusions: In this study, the proteomic changes in bronchoalveolar lavage of DBRI patients were distinct from other NIMP exposure associated lung diseases, while changes in AME overlapped those observed for HP patient samples. Some of the proteins identified in this study, semenogelin and histone 4, could function as diagnostic markers for differential diagnosis between DBRI and HP-like conditions.

This article is from PLoS ONE , volume 9 . Abstract Background: Hyperresponsiveness to inhaled non-infectious microbial particles (NIMPs) has been associated with illnesses in the airways. Hypersensitivity pneumonitis (HP) is considered to be the prototype for these NIMPs-related diseases; however, there is no consensus on the definitions or diagnostic criteria for HP and the spectrum of related illnesses. Methods and Findings: In order to identify the possible diagnostic markers for illnesses associated with NIMPs in alveolar lining fluid, we performed a proteomic analysis using a two-dimensional difference gel electrophoresis on bronchoalveolar lavage (BAL) fluid from patients with exposure to NIMPs in the context of damp building-related illness (DBRI) or conditions on the borderline to acute HP, designated here as agricultural type of microbial exposure (AME). Samples from patients with HP and sarcoidosis (SARC) were included for reference. Results were compared to results of healthy subjects (CTR). Western blot was used for validation of potential marker proteins from BAL fluid and plasma. Protein expression patterns suggest a close similarity between AME and HP, while DBRI was similar to CTR. However, in DBRI the levels of the inflammation associated molecules galectin-3 and alpha-1-antitrypsin were increased. A novel finding emerging from this study was the increases of semenogelin levels in BAL fluid from patients with AME, HP and SARC. Histone 4 levels were increased in AME, HP and SARC. Elevated plasma levels of histone 2B were detected in HP and SARC, suggesting it to be a potential blood indicator for inflammatory diseases of the lungs. Conclusions: In this study, the proteomic changes in bronchoalveolar lavage of DBRI patients were distinct from other NIMP exposure associated lung diseases, while changes in AME overlapped those observed for HP patient samples. Some of the proteins identified in this study, semenogelin and histone 4, could function as diagnostic markers for differential diagnosis between DBRI and HP-like conditions.

This article is from Particle and Fibre Toxicology , volume 9 . Abstract Particle toxicology arose in order to understand the mechanisms of adverse effects of 3 major particle types that had historically exerted the greatest toll of ill-health—quartz, coal and asbestos. By the middle of the last century rat inhalation studies had been carried out and the pathology documented, but true mechanistic particle toxicology did not really take off until the 1970s when cell culture techniques became available. By the 1980s glass fibres were a major focus of interest and attempts to develop a structure-toxicity paradigm centred on biopersistence. In the 1990s environmental particles dominated the particle toxicology agenda and the cardiovascular system emerged as a target for inhaled particles, raising new challenges for particle toxicologists. We are currently in the era of nanotoxicology where a large and diverse range of new nanoparticles types are under scrutiny.

Philip Morris Records; memo; extr, extra

Philip Morris Records; memo; extr, extra

Philip Morris Records; memo; extr, extra; marg, marginalia

Philip Morris Records; bibliography; budget; budget review; form; research proposal, scientific; resume; extr, extra; marg, marginalia

A mathematical description of particle clearance from the ciliated conducting airways (tracheobronchial region) of the lungs in rats was developed assuming that particles on the mucus blanket behave as a fluid and adhere to principles of fluid flow described by continuity equation. Effective particle transport velocities for given generations of airways were estimated from reported tracheal transport velocities. Using typical rat airway geometry and estimated particle transport velocities solutions of sets of rate equations for transport from each generation of airways were summed to estimate total particle clearance from the tracheobronchial region of the lung as a function of time. We used a wide range of aerosol particle size distribution data (MMAD ranging from 0.1 to 4.2 mm, and sg from 1 to 2.7) and concentration data from several investigators to predict short term, tracheobronchial clearance (retention) in rats and compared our predictions with their retention measurements. Based on an average of 17 simulations of tracheobronchial clearance the average difference between predicted and observed fractional retention of initial particle burden was 4.9%, with a tendency toward under prediction of clearance of particles 3.0 mm.