PubMed Health⌕ Search

Biomedical subjects

William Macnee

Publications and source records attributed to William Macnee.

9 recordsLinked to original sources
PubMed2005

Do inhaled carbon nanoparticles translocate directly into the circulation in humans?

RATIONALE: Increased exposure to particulate air pollution (PM(10)) is a risk factor for death and hospitalization with cardiovascular disease. It has been suggested that the nanoparticulate component of PM(10) is capable of translocating into the circulation with the potential for direct effects on the vasculature. OBJECTIVE: The study's aim was to determine the extent to which inhaled technetium-99m ((99m)Tc)-labeled carbon nanoparticles (Technegas) were able to access the systemic circulation. METHODS AND MAIN RESULTS: Ten healthy volunteers inhaled Technegas and blood samples were taken sequentially over the following 6 h. Technegas particles were 4-20 nm in diameter and aggregated to a median particle diameter of approximately 100 nm. Radioactivity was immediately detected in blood, with levels increasing over 60 min. Thin-layer chromatography of whole blood identified a species that moved with the solvent front, corresponding to unbound (99m)Tc-pertechnetate, which was excreted in urine. There was no evidence of particle-bound (99m)Tc at the origin. gamma Camera images demonstrated high levels of Technegas retention (95.6 +/- 1.7% at 6 h) in the lungs, with no accumulation of radioactivity detected over the liver or spleen. CONCLUSIONS: The majority of (99m)Tc-labeled carbon nanoparticles remain within the lung up to 6 h after inhalation. In contrast to previous published studies, thin-layer chromatography did not support the hypothesis that inhaled Technegas carbon nanoparticles pass directly from the lungs into the systemic circulation.

Adult↗
PubMed2005

Proposal for a multidimensional staging system for chronic obstructive pulmonary disease.

The severity of chronic obstructive pulmonary disease (COPD) is currently assessed using a single physiological measurement, the forced expiratory volume in 1s (FEV1). COPD, however, has complex effects on other aspects of respiratory function, and in many patients is associated with important systemic changes. We hypothesized that a multidimensional staging system for COPD could provide a more complete assessment of the disease's impact. We considered over 40 potential staging variables, evaluating them according to sensitivity to change, measured reproducibly, independence of the information they provide and prognostic value. We finally selected three: FEV1 (including arterial blood gas measurements when FEV1 falls below 35% predicted), Medical Research Council dyspnea scale and body mass index (BMI). Each measure correlates independently with prognosis in COPD, is supported by a significant body of literature and serves as a surrogate for other potentially important variables. We then used principal components analysis (PCA) to determine the degree of association between 30 of the potential variables measured in 813 stable COPD patients. Using PCA, six groups of measurements defined independent categories of patient information: pulmonary function (including FEV1), symptoms of cough and sputum, dyspnea, health status, bronchodilator reversibility and BMI. These include the three principal variables selected for the staging system. Although the staging boundaries were based on existing literature, they have proven useful in predicting survival. We conclude that a multidimensional grading system is useful to assess the impact of COPD.

Age Factors↗
PubMed2004

Cigarette smoke alters chromatin remodeling and induces proinflammatory genes in rat lungs.

Cigarette smoke-triggered inflammation is considered to play a central role in the development of chronic obstructive pulmonary disease by a mechanism that may involve enhanced proinflammatory gene transcription. Histone acetylation and deacetylation is a key regulator of the specificity and duration of gene transcription. Disruption in the nuclear histone acetylation:deacetylation balance (chromatin remodeling) may result in excessive transcription of specific proinflammatory genes in the lungs. In this study we show that cigarette smoke exposure results in an influx of inflammatory cells and chromatin modifications in rat lungs. This was associated with an increase in the active phosphorylated form of p38 mitogen-activated protein kinase concomitant with increased histone 3 phospho-acetylation, histone 4 acetylation, and increased DNA binding of the redox-sensitive transcription factor nuclear factor-kappaB, independent of inhibitory protein-kappaB degradation, and activator protein 1. We also observed decreased histone deacetylase 2 activity, which is due to protein modification by aldehydes and nitric oxide products present in cigarette smoke. Furthermore, we show that corticosteroid treatment has no effect on smoke-induced proinflammatory mediator release. These findings suggest a possible molecular mechanism by which cigarette smoke drives proinflammatory gene transcription and an inflammatory response in the lungs.

Acetylation↗