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Kevin Gibson

Publications and source records attributed to Kevin Gibson.

4 recordsLinked to original sources

Up-regulation and profibrotic role of osteopontin in human idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disorder characterized by fibroproliferation and excessive accumulation of extracellular matrix in the lung. METHODS AND FINDINGS: Using oligonucleotide arrays, we identified osteopontin as one of the genes that significantly distinguishes IPF from normal lungs. Osteopontin was localized to alveolar epithelial cells in IPF lungs and was also significantly elevated in bronchoalveolar lavage from IPF patients. To study the fibrosis-relevant effects of osteopontin we stimulated primary human lung fibroblasts and alveolar epithelial cells (A549) with recombinant osteopontin. Osteopontin induced a significant increase of migration and proliferation in both fibroblasts and epithelial cells. Epithelial growth was inhibited by the pentapeptide Gly-Arg-Gly-Asp-Ser (GRGDS) and antibody to CD44, while fibroproliferation was inhibited by GRGDS and antibody to alphavbeta3 integrin. Fibroblast and epithelial cell migration were inhibited by GRGDS, anti-CD44, and anti-alphavbeta3. In fibroblasts, osteopontin up-regulated tissue inhibitor of metalloprotease-1 and type I collagen, and down-regulated matrix metalloprotease-1 (MMP-1) expression, while in A549 cells it caused up-regulation of MMP-7. In human IPF lungs, osteopontin colocalized with MMP-7 in alveolar epithelial cells, and application of weakest link statistical models to microarray data suggested a significant interaction between osteopontin and MMP-7. CONCLUSIONS: Our results provide a potential mechanism by which osteopontin secreted from the alveolar epithelium may exert a profibrotic effect in IPF lungs and highlight osteopontin as a potential target for therapeutic intervention in this incurable disease.

Bronchoalveolar Lavage Fluid↗

Use of CT morphometry to detect changes in lung weight and gas volume.

STUDY OBJECTIVES: CT estimates of lung density have been used to estimate the extent and severity of emphysema. The present study was designed to test the hypothesis that quantitative CT can track the changes that occur in diffuse lung disease. DESIGN: The study was based on five patients with pulmonary alveolar proteinosis (PAP) who underwent lung lavage. Pulmonary function was measured before and after each individual lung lavage, and the CT scans before and after lavage were used to compare total lung volume, airspace volume, lung weight, and regional lung inflation. The dry weight of proteinaceous material lavaged from the lung was measured and compared to the change in CT lung weight. RESULTS: All the patients showed improvements in dyspnea, percentage of predicted diffusion capacity of the lung for carbon monoxide, and FVC. There was no change in CT-measured total lung volume or airspace volume, but there was a reduction in lung weight following lavage (p = 0.001), which correlated with the dry weight of the lavage effluent (R(2) = 0.73). Therefore, there was a shift in the regional lung inflation toward a more inflated lung with a corresponding increase in the mean lung inflation (p = 0.001). CONCLUSION: These data show that quantitative CT can objectively track the changes in lung weight and airspace inflation produced by a standard intervention in PAP, and we postulate that it can provide similar information about the progression of other diffuse lung diseases.

Bronchoalveolar Lavage↗

Contrasting role morality and professional morality: implications for practice.

The notion of role morality suggests individuals may adopt a different morality depending on the roles they undertake. Investigating role morality is important, since the mentality of role morality may allow agents to believe they can abdicate moral responsibility when acting in a role. This is particularly significant in the literature dealing with professional morality where professionals, because of their special status, may find themselves at odds with their best moral judgments. Here I tell four stories and draw out some distinctions. I conclude that role morality is a genuine and useful distinction. However, I suggest that the purported distinction between role morality and professional morality is over-determined. Therefore, alleged conflicts between the demands of role and profession (such as the different pressures on Pinto designers as employees and as engineers) are not conflicts between different kinds of demands, but rather conflicts arising from divergent roles that most workers will encounter regularly. Another analytical perspective is to look at moral choices at work in terms of power and the ability to bring about change. Finally, I draw the implication that we should stress moral awareness at a fairly abstract level for all employees and reinforce the moral primacy of individual choice.

Codes of Ethics↗