Introduction: Accelerated cellular senescence has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Increased endoplasmic reticulum (ER) stress response has been demonstrated in epithelial cells in IPF, during which autophagy removes expanded and disorganized ER. Autophagy plays an important regulatory role in senescence through homeostatic degradation of damaged cellular proteins as a central component of the integrated stress response. Thus, we hypothesized that insufficient autophagy is involved in the acceleration of cellular senescence of epithelial cells in IPF.Methods: Cellular senescence was evaluated by immunohistochemical staining in paraffin embedded IPF lung tissues of p21, a senescence associated cyclin-dependent kinase inhibitor. Immunohistochemical evaluations of ubiquitinated protein and autophagy related proteins, including Beclin1, LC3, and p62, were also performed. Immunostaining was assessed by counting total and positively staining cells in five randomly selected lung fields of type II alveolar epithelial cells (AECII), normal airway, fibroblastic foci, mild to moderate fibrosis, dense fibrosis, and honeycomb change at a magnification of Χ400 in each case (n=5 in control, n=5 in IPF) and average percentage of positive staining were scored in a semi-quantitative fashion; 0 (less than 10%), 1 (11~49%), and 2 (more than 50%). Proteasome inhibitor MG132, autophagy inhibitior bafilomycin A (BFA), and mTOR inhibitor Torin1treatments as well as transfection of LC3 siRNA were performed to explore the regulatory roles of the proteasome and autophagy in accumulations of both ubiquitinated proteins and p62 in in vitro models of human bronchial epithelial cells (HBEC).Results: We demonstrated that proliferating metaplastic cells in IPF highly expressed both ubiquitinated proteins and p62. p21 expression was also observed in metaplastic epithelial cells. AECII in relatively normal areas of IPF were also stressed by means of ubiquitin staining, however concomitant LC3 expression, indicating autophagy activation, may explain why p21 expression was not observed in those cells. An important role for p21 in the progression of cell senescence relating to insufficient autophagy following 3MA treatment was demonstrated in HBEC. MG132 increased accumulations of both ubiquitinated proteins and p62 in HBEC, but these decreased in the presence of Torin1. LC3 knockdown also enhanced accumulations of both ubiquitinated proteins and p62.Conclusions: These findings suggest that insufficient autophagy is a potent underlying pathology of accelerated cellular senescence and a promising clue to understanding the molecular mechanisms for the development of effective therapeutic intervention in the senescence associated lung disease, IPF.

[Purpose] The purpose of this study was to assess the reliability and construct validity of three observational measures of mobility for elderly inpatients with dementia. [Subjects and Methods] The subjects were 51 inpatients, who were aged 60 or over and diagnosed as having dementia (mean age ± SD, 84.4 ± 6.9; range 60-96 years). The Physical Performance and Mobility Examination (PPME), Hierarchical Assessment of Balance and Mobility (HABAM) and the Rivermead Mobility Index (RMI) were chosen as a measure to observe the mobility behaviors of persons with dementia, and the reliability and construct validity were investigated.[Results] Intraclass correlation coefficients (ICC) showed that all scales had a good inter-rater reliability (ICC>0.8) and testretest reliability (ICC>0.9). These scales significantly correlated with symptoms of dementia. Principal component analysis found a uni-factorial nature for the PPME and HABAM.[Conclusion] PPME and HABAM may be suitable measurement tools of mobility for elderly inpatients with dementia. Key words: elderly inpatient with dementia, mobility, measurement propertyPhysical performance and mobility examination PPME hierarchical assessment of balance and mobility HABAM rivermead mobility index RMI 3 0.8 0.9 PPME HABAM 1 3: 11-13 706-0023 TEL 0863-81-71252)3)

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According to the Science Council of Japan, the multifunctional roles of fisheries and fishery communities are classified into 5 categories; 1) to provide foods and other natural resources, 2) to preserve natural environment, 3) to form and maintain local communities, 4) to protect people's lives and their properties and 5) to provide living and communication spaces to the people. The authors have studied how the multifunctionality is recognized and aware of by the people of Hakodate City, where fisheries are prosperous. The study consists of the following three steps: 1. The correlations between the recognitions for the multifunctional roles and the awareness of the environments. 2. The value of the multifunctional roles of fisheries and fishery communities are estimated with the Contingent Valuation Method (CVM). 3. The research on the role to provide communication spaces between the urban and rural areas among the multifunctional roles are deepened.