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Pulmonary fibrosis is a chronic inflammatory disorder characterized by diffuse fibrous remodeling of alveolar spaces. Although much interest is focused on mechanisms of the inflammatory process in pulmonary fibrosis, little is known about the repair and regenerative process. Hepatocyte growth factor (HGF), originally discovered as a mitogen for hepatocyte regeneration, is now recognized as a multifunctional mesenchymal factor for epithelial regeneration, including the regeneration of alveolar type II epithelial cells. Involvement of HGF and its receptor (c-met) is evident in animal models of acute lung injury produced by hydrochloride inhalation. We studied the role of HGF in patients with idiopathic pulmonary fibrosis (IPF) (25 cases), lung fibrosis associated with rheumatoid arthritis (22 cases), and sarcoidosis (39 cases). Immunohistochemical evaluation demonstrated that hyperplastic alveolar type II epithelial cells, as well as alveolar macrophages, were strongly stained with anti-HGF antibody in tissues of patients with IPF. The concentration of HGF in bronchoalveolar lavage fluid (BALF) was significantly higher than in normal controls (0.23 +/- 0.09 pg/microg) in patients with IPF (0.77 +/- 0.88 pg of HGF/microg of albumin, P < 0.001), lung fibrosis associated with rheumatoid arthritis (0.50 +/- 0.64 pg/microg, P < 0.01), and sarcoidosis (0.41 +/- 0.61 pg/microg, P < 0.05). In situ hybridization revealed mRNA for HGF in alveolar macrophages (especially small monocytelike macrophages). These results indicate that the increase in HGF concentration in patients' peripheral air spaces is due to augmented HGF production by alveolar epithelial cells and alveolar macrophages. HGF, through a paracrine mechanism, may play an important role in the repair and healing of the inflammatory lung damage in pulmonary fibrosis.

SUMMARYThe accuracy of drag prediction in unstructured mesh CFD solver of TAS (Tohoku University Aerodynamic Simulation) code is discussed using a drag decomposition method. The drag decomposition method decomposes total drag into wave, profile, induced and spurious drag components, the latter resulting from numerical diffusion and errors. The mesh resolution analysis is conducted by the drag decomposition method. The effect of an advanced unstructured mesh scheme of U-MUSCL reconstruction is also investigated by the drag decomposition method. The computational results show that the drag decomposition method reliably predicts drag and is capable of meaningful drag decomposition. The accuracy of drag prediction is increased by eliminating the spurious drag component from the total drag. It is also confirmed that the physical drag components are almost independent of the mesh resolution and scheme modification.

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