||Yoshihara Kazufumi, Tanabe Hiroki C., Kawamichi Hiroaki, Koike Takahiko, Yamazaki Mika, Sudo Nobuyuki, Sadato Norihiro, Neural correlates of fear-induced sympathetic response associated with the peripheral temperature change rate, NEUROIMAGE, 10.1016/j.neuroimage.2016.04.040, 134, 522-531, 2016.07, 恐怖による交感神経活動に関する脳活動および脳内ネットワークを明らかにした.
||Kawamichi Hiroaki, Yoshihara Kazufumi, Sugawara Sho K., Matsunaga Masahiro, Makita Kai, Hamano Yuki H., Tanabe Hiroki C., Sadato Norihiro, Helping behavior induced by empathic concern attenuates anterior cingulate activation in response to others' distress, SOCIAL NEUROSCIENCE, 10.1080/17470919.2015.1049709, 11, 2, 109-122, 2016.03.
||Kawamichi Hiroaki, Kitada Ryo, Yoshihara Kazufumi, Takahashi Haruka, Sadato Norihiro, Interpersonal touch suppresses visual processing of aversive stimuli, FRONTIERS IN HUMAN NEUROSCIENCE, 10.3389/fnhum.2015.00164, 9, 2015.04.
||Kawamichi Hiroaki, Kazufumi Yoshihara, Sasaki Akihiro T., Sugawara Sho K., Tanabe Hiroki C., Shinohara Ryoji, Sugisawa Yuka, Tokutake Kentaro, Mochizuki Yukiko, Anme Tokie, Sadato Norihiro, Perceiving active listening activates the reward system and improves the impression of relevant experiences, SOCIAL NEUROSCIENCE, 10.1080/17470919.2014.954732, 10, 1, 16-26, 2015.01.
||Kitada Ryo, Kazufumi Yoshihara, Sasaki Akihiro T., Hashiguchi Maho, Kochiyama Takanori, Sadato Norihiro, The Brain Network Underlying the Recognition of Hand Gestures in the Blind: The Supramodal Role of the Extrastriate Body Area, JOURNAL OF NEUROSCIENCE, 10.1523/JNEUROSCI.0500-14.2014, 34, 30, 10096-10108, 2014.07.
||Kazufumi Yoshihara, Tetsuya Hiramoto, Takakazu Oka, Chiharu Kubo, Nobuyuki Sudo, Effect of 12 weeks of yoga training on the somatization, psychological symptoms, and stress-related biomarkers of healthy women, BioPsychoSocial Medicine, 10.1186/1751-0759-8-1, 8, 1, 2014.01, Background: Previous studies have shown that the practice of yoga reduces perceived stress and negative feelings and that it improves psychological symptoms. Our previous study also suggested that long-term yoga training improves stress-related psychological symptoms such as anxiety and anger. However, little is known about the beneficial effects of yoga practice on somatization, the most common stress-related physical symptoms, and stress-related biomarkers. We performed a prospective, single arm study to examine the beneficial effects of 12 weeks of yoga training on somatization, psychological symptoms, and stress-related biomarkers.Methods: We recruited healthy women who had no experience with yoga. The data of 24 participants who were followed during 12 weeks of yoga training were analyzed. Somatization and psychological symptoms were assessed before and after 12 weeks of yoga training using the Profile of Mood State (POMS) and the Symptom Checklist-90-Revised (SCL-90-R) questionnaires. Urinary 8-hydroxydeoxyguanosine (8-OHdG), biopyrrin, and cortisol levels were measured as stress-related biomarkers. The Wilcoxon signed-rank test was used to compare the stress-related biomarkers and the scores of questionnaires before and after 12 weeks of yoga training.Results: After 12 weeks of yoga training, all negative subscale scores (tension-anxiety, depression, anger-hostility, fatigue, and confusion) from the POMS and somatization, anxiety, depression, and hostility from the SCL-90-R were significantly decreased compared with those before starting yoga training. Contrary to our expectation, the urinary 8-OHdG concentration after 12 weeks of yoga training showed a significant increase compared with that before starting yoga training. No significant changes were observed in the levels of urinary biopyrrin and cortisol after the 12 weeks of yoga training.Conclusions: Yoga training has the potential to reduce the somatization score and the scores related to mental health indicators, such as anxiety, depression, anger, and fatigue. The present findings suggest that yoga can improve somatization and mental health status and has implications for the prevention of psychosomatic symptoms in healthy women.Trial registration: University Hospital Medical Information Network (UMIN CTR) UMIN000007868..
||Kazufumi Yoshihara, Tetsuya Hiramoto, Nobuyuki Sudo, Chiharu Kubo, Profile of mood states and stress-related biochemical indices in long-term yoga practitioners, BioPsychoSocial Medicine, 10.1186/1751-0759-5-6, 5, 2011.06, Background: Previous studies have shown the short-term or intermediate-term practice of yoga to be useful for ameliorating several mental disorders and psychosomatic disorders. However, little is known about the long-term influences of yoga on the mental state or stress-related biochemical indices. If yoga training has a stress-reduction effect and also improves an individual's mental states for a long time, long-term yoga practitioners may have a better mental state and lower stress-related biochemical indices in comparison to non-experienced participants. This study simultaneously examined the differences in mental states and urinary stress-related biochemical indices between long-term yoga practitioners and non-experienced participants.Methods: The participants were 38 healthy females with more than 2 years of experience with yoga (long-term yoga group) and 37 age-matched healthy females who had not participated in yoga (control group). Their mental states were assessed using the Profile of Mood States (POMS) questionnaire. The level of cortisol, 8-hydroxydeoxyguanosine (8-OHdG) and biopyrrin in urine were used as stress-related biochemical indices.Results: The average self-rated mental disturbance, tension-anxiety, anger-hostility, and fatigue scores of the long-term yoga group were lower than those of the control group. There was a trend toward a higher vigor score in the long-term yoga group than that in the control group. There were no significant differences in the scores for depression and confusion in the POMS between the two groups. The urine 8-OHdG concentration showed a trend toward to being lower in the long-term yoga group in comparison to the control group. There were no significant differences in the levels of urine biopyrrin or cortisol.Conclusions: The present findings suggest that long-term yoga training can reduce the scores related to mental health indicators such as self-rated anxiety, anger, and fatigue..
||Kazufumi Yoshihara, Hisakata Yamada, Akiko Hori, Toshiki Yajima, Chiharu Kubo, Yasunobu Yoshikai, IL-15 exacerbates collagen-induced arthritis with an enhanced CD4+ T cell response to produce IL-17, European Journal of Immunology, 10.1002/eji.200737229, 37, 10, 2744-2752, 2007.10, IL-15 is thought to be involved in the pathogenesis of rheumatoid arthritis (RA). We found that IL-15 plays an important role in the development of murine collagen-induced arthritis (CIA). The incidence and severity of CIA were slightly decreased in IL-15 KO mice but were increased in IL-15 Tg mice compared with wild-type (WT) mice. The levels of type II collagen (CII)-specific IL-17 production were significantly increased in IL-15 Tg mice compared with WT mice with CIA. Expression of IL-23R was up-regulated in CD4+ T cells in IL-15 Tg mice but down-regulated in IL-15 KO mice compared with WT mice. In correlation with the expression levels of IL-23R, IL-17 production by CD4+ Tcells in response to exogenous IL-23 was increased in IL-15 Tg mice compared with WT mice. Furthermore, exogenous IL-15 synergized with IL-23 to induce CII-specific IL-17 production by CD4+ T cells. in vitro. Taken together, these results indicate that IL-15 plays an important role in the progression of CIA through increasing antigen-specific IL-17 production by CD4+ T cells..
||K. Yoshihara, Toshiki Yajima, C. Kubo, Y. Yoshikai, Role of interleukin 15 in colitis induced by dextran sulphate sodium in mice, Gut, 10.1136/gut.2005.076000, 55, 3, 334-341, 2006.03, Background and aims: Interleukin (IL)-15 is a member of the IL-2 family, stimulating dendritic cells, natural killer (NK) cells, NK T cells and memory CD8+ T cells. IL-15 levels were elevated in the intestinal mucosa of inflammatory bowel diseases. Here we investigated the involvement of IL-15 in the pathogenesis of acute and chronic dextran sulphate sodium (DSS) induced colitis. Methods: IL-15 knockout (KO) mice and control C57BL/6 mice were used to induce colitis with DSS in their drinking water. Survival rate, clinical activity of diseases, extent of tissue damage, leucocyte population, and cytokine production of lamina propria (LP) cells of the large intestines were assessed. Results: IL-15 KO mice exhibited resistance to DSS induced acute colitis, as reflected by lower lethality, weight loss, clinical scores, and histological scores compared with those in control mice (p<0.05). The proportions of CD44high CD8+ T cells and NK cells in LP cells and levels of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, and IL-12p40 in culture supernatants of LP cells were reduced in IL-15 KO mice (p<0.05). In vivo depletion of CD8+ T cells and NK cells decreased levels of IFN-γ, TNF-α, and IL-12p40 in culture supernatants of LP cells in C57BL/6 mice (p<0.01). In chronic colitis, weight loss and clinical scores were improved and levels of IFN-γ, TNF-α, and IL-12p40 in culture supernatants of LP cells were also reduced in IL-15 KO mice (p<0.05). Conclusions: IL-15 plays an important role in the pathogenesis of both acute and chronic colitis induced by DSS in mice..
||Toshiki Yajima, Kazufumi Yoshihara, Kenji Nakazato, Shino Kumabe, Shigeo Koyasu, Subash Sad, Hao Shen, Hiroyuki Kuwano, Yasunobu Yoshikai, IL-15 regulates CD8+ T cell contraction during primary infection, Journal of Immunology, 10.4049/jimmunol.176.1.507, 176, 1, 507-515, 2006.01, During the course of acute infection with an intracellular pathogen, Ag-specific T cells proliferate in the expansion phase, and then most of the T cells die by apoptosis in the following contraction phase, but the few that survive become memory cells and persist for a long period of time. Although IL-15 is known to play an important role in long-term maintenance of memory CD8+ T cells, the potential roles of IL-15 in CD8+ T cell contraction are not known. Using an adoptive transfer system of OT-I cells expressing OVA257-264/Kb-specific TCR into control, IL-15 knockout (KO) and IL-15 transgenic (Tg) mice followed by challenge with recombinant Listeria monocytogenes expressing OVA, we found that the survival of CD44+CD62L-CD127- effector OT-I cells during the contraction phase is critically dependent on IL-15. In correlation with the expression level of Bcl-2 in OT-I cells, the number of OT-I cells was markedly reduced in IL-15 KO mice but remained at a high level in IL-15 Tg mice during the contraction phase, compared with control mice. In vivo administration of rIL-15 during the contraction phase in IL-15 KO mice inhibited the contraction of effector OT-I cells accompanied by up-regulation of Bcl-2 expression. Furthermore, enforced expression of Bcl-2 protected the majority of effector OT-I cells from death in IL-15 KO mice after infection. These results suggest that IL-15 plays a critical role in protecting effector CD8+ T cells from apoptosis during the contraction phase following a microbial infection via inducing antiapoptotic molecules..