Gelsolin expression is necessary for the development of modelled pulmonary inflammation and fibrosis.

BACKGROUND: Despite intense research efforts, the aetiology and pathogenesis of idiopathic pulmonary fibrosis remain poorly understood. Gelsolin, an actin-binding protein that modulates cytoskeletal dynamics, was recently highlighted as a likely disease modifier through comparative expression profiling and target prioritisation. METHODS: To decipher the possible role of gelsolin in pulmonary inflammation and fibrosis, immunocytochemistry on tissue microarrays of human patient samples was performed followed by computerised image analysis. The results were validated in the bleomycin-induced animal model of pulmonary inflammation and fibrosis using genetically-modified mice lacking gelsolin expression. Moreover, to gain mechanistic insights into the mode of gelsolin activity, a series of biochemical analyses was performed ex vivo in mouse embryonic fibroblasts. RESULTS: Increased gelsolin expression was detected in lung samples of patients with idiopathic interstitial pneumonia as well as in modelled pulmonary inflammation and fibrosis. Genetic ablation of gelsolin protected mice from the development of modelled pulmonary inflammation and fibrosis attributed to attenuated epithelial apoptosis. CONCLUSIONS: Gelsolin expression is necessary for the development of modelled pulmonary inflammation and fibrosis, while the caspase-3-mediated gelsolin fragmentation was shown to be an apoptotic effector mechanism in disease pathogenesis and a marker of lung injury.

Acquisition of high-risk behavior by African-American, Latino, and Caucasian middle-school students.

The purpose of this study was to measure the stages of acquisition of selected high-risk health behaviors in 768 randomly selected 7th- and 8th-graders in a Florida school district. Specific high-risk health behaviors included use of alcohol, tobacco, and drugs, fighting and weapon carrying, and suicide ideation. Analysis indicated few behaviors that were significantly different when African-American and Latino students were compared with Caucasian students. The most weapon carrying was reported by Latinos. Fewer Caucasian students than their minority peers used inhalants. Knowledge of stages of acquisition among small diverse samples may assist school personnel to intervene during the inculcation process with appropriate responsive programs.