Browsing by Author "Kyoto University Faculty of Medicine"

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    Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome
    (2018-02-15) Marisa Oliveira; Worachart Lert-itthiporn; Bruno Cavadas; Verónica Fernandes; Ampaiwan Chuansumrit; Orlando Anunciação; Isabelle Casademont; Fanny Koeth; Marina Penova; Kanchana Tangnararatchakit; Chiea Chuen Khor; Richard Paul; Prida Malasit; Fumihiko Matsuda; Etienne Simon-Lorière; Prapat Suriyaphol; Luisa Pereira; Anavaj Sakuntabhai; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; A-Star, Genome Institute of Singapore; Kyoto University Faculty of Medicine; National University of Singapore; Faculty of Medicine, Ramathibodi Hospital, Mahidol University; Thailand National Center for Genetic Engineering and Biotechnology; Faculty of Medicine, Siriraj Hospital, Mahidol University; CNRS Centre National de la Recherche Scientifique; Universidade do Porto; Institut Pasteur, Paris; Pasteur Kyoto International Joint Research Unit for Integrative Vaccinomics
    © 2018 Oliveira et al. Ethnic diversity has been long considered as one of the factors explaining why the severe forms of dengue are more prevalent in Southeast Asia than anywhere else. Here we take advantage of the admixed profile of Southeast Asians to perform coupled association-admixture analyses in Thai cohorts. For dengue shock syndrome (DSS), the significant haplotypes are located in genes coding for phospholipase C members (PLCB4 added to previously reported PLCE1), related to inflammation of blood vessels. For dengue fever (DF), we found evidence of significant association with CHST10, AHRR, PPP2R5E and GRIP1 genes, which participate in the xenobiotic metabolism signaling pathway. We conducted functional analyses for PPP2R5E, revealing by immunofluorescence imaging that the coded protein co-localizes with both DENV1 and DENV2 NS5 proteins. Interestingly, only DENV2-NS5 migrated to the nucleus, and a deletion of the predicted top-linking motif in NS5 abolished the nuclear transfer. These observations support the existence of differences between serotypes in their cellular dynamics, which may contribute to differential infection outcome risk. The contribution of the identified genes to the genetic risk render Southeast and Northeast Asian populations more susceptible to both phenotypes, while African populations are best protected against DSS and intermediately protected against DF, and Europeans the best protected against DF but the most susceptible against DSS.
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    Prostaglandin E2-prostoglandin E receptor subtype 4 (EP4) signaling mediates UV irradiation-induced systemic immunosuppression
    (2011-04-19) Kitipong Soontrapa; Tetsuya Honda; Daiji Sakata; Chengcan Yao; Takako Hirata; Shohei Hori; Toshiyuki Matsuoka; Yoshihiro Kita; Takao Shimizu; Kenji Kabashima; Shuh Narumiya; Kyoto University Faculty of Medicine; Mahidol University; Riken Research Center for Allergy and Immunology; Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
    UV radiation induces systemic immunosuppression. Because nonsteroidal anti-inflammatory drugs suppress UV-induced immunosuppression, prostanoids have been suspected as a crucial mediator of this UV effect. However, the identity of the prostanoid involved and its mechanism of action remain unclear. Here, we addressed this issue by subjecting mice deficient in each prostanoid receptor individually or mice treated with a subtype-specific antagonist to UV irradiation. Mice treated with an antagonist for prostaglandin E receptor subtype 4 (EP4), but not those deficient in other prostanoid receptors, show impaired UV-induced immunosuppression, whereas administration of an EP4 agonist rescues the impairment of the UV-induced immunosuppression in indomethacin-treated mice. The EP4 antagonist treatment suppresses an increase in the number of CD4 + /forkhead box P3-positive (Foxp3 + ) regulatory T cells (Treg cells) in the peripheral lymph nodes (LNs) and dendritic cells expressing DEC205 in the LNs and the skin after UV irradiation. Furthermore, the EP4 antagonist treatment down-regulates UV-induced expression of receptor activator of NF-κB ligand (RANKL) in skin keratinocytes. Finally, administration of anti-RANKL antibody abolishes the restoration of UV-induced immunosuppression by EP4 agonism in indomethacin-treated mice. Thus, prostaglandin E 2 (PGE 2 )-EP4 signaling mediates UV-induced immunosuppression by elevating the number of Treg cells through regulation of RANKL expression in the epidermis.
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    Sarcopenia in Asia: Consensus report of the Asian working group for sarcopenia
    (2014-01-01) Liang Kung Chen; Li Kuo Liu; Jean Woo; Prasert Assantachai; Tung Wai Auyeung; Kamaruzzaman Shahrul Bahyah; Ming Yueh Chou; Liang Yu Chen; Pi Shan Hsu; Orapitchaya Krairit; Jenny S.W. Lee; Wei Ju Lee; Yunhwan Lee; Chih Kuang Liang; Panita Limpawattana; Chu Sheng Lin; Li Ning Peng; Shosuke Satake; Takao Suzuki; Chang Won Won; Chih Hsing Wu; Si Nan Wu; Teimei Zhang; Ping Zeng; Masahiro Akishita; Hidenori Arai; Veterans General Hospital-Taipei; Chinese University of Hong Kong; Mahidol University; University of Malaya; Veterans General Hospital-Kaohsiung Taiwan; Taichung Hospital; Ajou University, School of Medicine; Khon Kaen University; Veterans General Hospital-Taichung Taiwan; National Center for Geriatrics and Gerontology - National Institute for Longevity Sciences; Kyung Hee University; National Cheng Kung University Hospital; Ministry of Health of People's Republic of China; Kyoto University Faculty of Medicine; University of Tokyo
    Sarcopenia, a newly recognized geriatric syndrome, is characterized by age-related decline of skeletal muscle plus low muscle strength and/or physical performance. Previous studies have confirmed the association of sarcopenia and adverse health outcomes, such as falls, disability, hospital admission, long term care placement, poorer quality of life, and mortality, which denotes the importance of sarcopenia in the health care for older people. Despite the clinical significance of sarcopenia, the operational definition of sarcopenia and standardized intervention programs are still lacking. It is generally agreed by the different working groups for sarcopenia in the world that sarcopenia should be defined through a combined approach of muscle mass and muscle quality, however, selecting appropriate diagnostic cutoff values for all the measurements in Asian populations is challenging. Asia is a rapidly aging region with a huge population, so the impact of sarcopenia to this region is estimated to be huge as well. Asian Working Group for Sarcopenia (AWGS) aimed to promote sarcopenia research in Asia, and we collected the best available evidences of sarcopenia researches from Asian countries to establish the consensus for sarcopenia diagnosis. AWGS has agreed with the previous reports that sarcopenia should be described as low muscle mass plus low muscle strength and/or low physical performance, and we also recommend outcome indicators for further researches, as well as the conditions that sarcopenia should be assessed. In addition to sarcopenia screening for community-dwelling older people, AWGS recommends sarcopenia assessment in certain clinical conditions and healthcare settings to facilitate implementing sarcopenia in clinical practice. Moreover, we also recommend cutoff values for muscle mass measurements (7.0 kg/m2 for men and 5.4 kg/m2 for women by using dual X-ray absorptiometry, and 7.0 kg/m2 for men and 5.7 kg/m2 for women by using bioimpedance analysis), handgrip strength (<26 kg for men and <18 kg for women), and usual gait speed (<0.8 m/s). However, a number of challenges remained to be solved in the future. Asia is made up of a great number of ethnicities. The majority of currently available studies have been published from eastern Asia, therefore, more studies of sarcopenia in south, southeastern, and western Asia should be promoted. On the other hand, most Asian studies have been conducted in a cross-sectional design and few longitudinal studies have not necessarily collected the commonly used outcome indicators as other reports from Western countries. Nevertheless, the AWGS consensus report is believed to promote more Asian sarcopenia research, and most important of all, to focus on sarcopenia intervention studies and the implementation of sarcopenia in clinical practice to improve health care outcomes of older people in the communities and the healthcare settings in Asia. © 2014 American Medical Directors Association, Inc.