| 1. |
Motoharu Gondo, Keisuke Kawai, Yoshiya Moriguchi, Akio Hiwatashi, Shu Takakura, Kazufumi Yoshihara, Chihiro Morita, Makoto Yamashita, Sanami Eto, Nobuyuki Sudo, Effects of integrated hospital treatment on the default mode, salience, and frontal-parietal networks in anorexia nervosa: A longitudinal resting-state functional magnetic resonance imaging study., PloS one, 10.1371/journal.pone.0283318, 18, 5, e0283318, 2023.05, The psychopathology of patients with anorexia nervosa has been hypothesized to involve inappropriate self-referential processing, disturbed interoceptive awareness, and excessive cognitive control, including distorted self-concern, disregard of their own starvation state, and extreme weight-control behavior. We hypothesized that the resting-state brain networks, including the default mode, salience and frontal-parietal networks, might be altered in such patients, and that treatment might normalize neural functional connectivity, with improvement of inappropriate self-cognition. We measured resting-state functional magnetic resonance images from 18 patients with anorexia nervosa and 18 healthy subjects before and after integrated hospital treatment (nourishment and psychological therapy). The default mode, salience, and frontal-parietal networks were examined using independent component analysis. Body mass index and psychometric measurements significantly improved after treatment. Before treatment, default mode network functional connectivity in the retrosplenial cortex and salience network functional connectivity in the ventral anterior insula and rostral anterior cingulate cortex were decreased in anorexia nervosa patients compared with those in controls. Interpersonal distrust was negatively correlated with salience network functional connectivity in the rostral anterior cingulate cortex. Default mode network functional connectivity in the posterior insula and frontal-parietal network functional connectivity in the angular gyrus were increased in anorexia nervosa patients compared with those in controls. Comparison between pre- and post-treatment images from patients with anorexia nervosa exhibited significant increases in default mode network functional connectivity in the hippocampus and retrosplenial cortex, and salience network functional connectivity in the dorsal anterior insula following treatment. Frontal-parietal network functional connectivity in the angular cortex showed no significant changes. The findings revealed that treatment altered the functional connectivity in several parts of default mode and salience networks in patients with anorexia nervosa. These alterations of neural function might be associated with improvement of self-referential processing and coping with sensations of discomfort following treatment for anorexia nervosa.. |
| 2. |
Tomoe Nishihara, Kazufumi Yoshihara, Ayako Ohashi, Mika Kuroiwa, Nobuyuki Sudo, Differences in the presentation of COVID-19-related psychosocial stress and general psychological distress and the relation between the number of care days and these symptoms among Japanese ward staff working exclusively with COVID-19 and support staff., BioPsychoSocial medicine, 10.1186/s13030-023-00272-7, 17, 1, 17-17, 2023.04, BACKGROUND: Psychological distress has been frequently observed in frontline healthcare workers under stress during the coronavirus disease 2019 (COVID-19) epidemic; however, it is unclear if there are differences in the stress and symptoms experienced by staff members who work exclusively in a COVID-19 ward and support staff temporarily deployed to a COVID-19 ward. The present study investigated psychosocial stress specific to the care for patients with COVID-19 and psychological distress among ward staff working exclusively with COVID-19 and temporary support staff. METHODS: The participants were full-time nurses and doctors working in COVID-19 wards or the ICU who provided face-to-face care to patients with COVID-19 during the COVID-19 outbreak in February of 2021. The data of 67 staff members (21 exclusively working with Covid-19 patients (group A) and 46 in the temporary support group (group B)) was available for study. Psychosocial stress specific to healthcare professionals during this COVID-19 outbreak (Tokyo Metropolitan Distress Scale for Pandemic [TMDP]) and general psychological distress (K6) were assessed. RESULTS: The K6 score was significantly lower in group B than in group A (p = .006), but no significant difference was found in the total score of TMDP or its subscales. Positive correlations were found between TMDP and K6 for group B (p = .011), as was the number of days of care on TMDP-social (rs = .456, p = .001). CONCLUSION: Even though support staff members experienced lower psychological distress than staff working exclusively with COVID-19, COVID-19-related psychosocial stress specific to HCWs was comparable. The support staff also presented psychological distress associated with psychosocial stress specific to healthcare professionals during this COVID-19 outbreak, and the COVID-19-related social stress was enhanced as the number of working days increased. Our results show that all staff, not only those working exclusively with COVID-19 patients but also other support staff should be provided with care focusing on COVID-19-related psychosocial occupational stress.. |
| 3. |
Tomoe Nishihara, Kazufumi Yoshihara, Ayako Ohashi, Mika Kuroiwa, Nobuyuki Sudo, Occupational stress, psychological distress, physical symptoms, and their interrelationships among frontline nurses caring for COVID-19 patients in Japan., Medicine, 10.1097/MD.0000000000031687, 101, 48, e31687, 2022.12, This study aimed to identify occupational stress, psychosomatic symptoms, psychological distress, and their correlations among frontline nurses during and after the first peak of the coronavirus disease 2019 (COVID-19) outbreak in Japan. Sixteen frontline nurses, aged 25 to 52 years, working in a ward with COVID-19 patients participated in this study. Two months after the peak of the first wave of the COVID-19 outbreak in Japan, the COVID-19-related occupational stress scale (COS; questionnaire items: fear of infection and increased workload) and physical symptom scale (PS; questionnaire items: gastrointestinal symptoms, pain, appetite loss, and insomnia) were assessed. The degree of general psychological distress was evaluated using the 6-item Kessler Scale (K6). Simultaneously, participants were asked to recall their condition during the peak period of the first wave and rate it using the same scale. K6 was positively correlated with COS and PS during the peak period (rs = 0.574, P = .020 and rs = 0.587, P = .017, respectively). Increased workload was positively correlated with the K6 score both during and after the peak period (rs = 0.869, P |
| 4. |
Naoki Hirabayashi, Jun Hata, Yoshihiko Furuta, Tomoyuki Ohara, Mao Shibata, Yoichiro Hirakawa, Fumio Yamashita, Kazufumi Yoshihara, Takanari Kitazono, Nobuyuki Sudo, Toshiharu Ninomiya, Association Between Diabetes and Gray Matter Atrophy Patterns in a General Older Japanese Population: The Hisayama Study., Diabetes care, 10.2337/dc21-1911, 45, 6, 1364-1371, 2022.06, OBJECTIVE: To examine the association between diabetes and gray matter atrophy patterns in a general older Japanese population. RESEARCH DESIGN AND METHODS: In 2012, a total of 1,189 community-dwelling Japanese aged ≥65 years underwent brain MRI scans. Regional gray matter volumes (GMV) and intracranial volume (ICV) were measured by applying voxel-based morphometry (VBM) methods. The associations of diabetes and related parameters with the regional GMV/ICV were examined using an ANCOVA. The regional gray matter atrophy patterns in the subjects with diabetes or elevated fasting plasma glucose (FPG) or 2 h postload glucose (2hPG) levels were investigated using VBM. RESULTS: Subjects with diabetes had significantly lower mean values of GMV/ICV in the frontal lobe, temporal lobe, insula, deep gray matter structures, and cerebellum than subjects without diabetes after adjusting for potential confounders. A longer duration of diabetes was also significantly associated with lower mean values of GMV/ICV in these brain regions. The multivariable-adjusted mean values of the temporal, insular, and deep GMV/ICV decreased significantly with elevating 2hPG levels, whereas higher FPG levels were not significantly associated with GMV/ICV of any brain regions. In the VBM analysis, diabetes was associated with gray matter atrophy in the bilateral superior temporal gyri, right middle temporal gyrus, left inferior temporal gyrus, right middle frontal gyrus, bilateral thalami, right caudate, and right cerebellum. CONCLUSIONS: The current study suggests that a longer duration of diabetes and elevated 2hPG levels are significant risk factors for gray matter atrophy in various brain regions.. |
| 5. |
Xueting Zhang, Kazufumi Yoshihara, Noriyuki Miyata, Tomokazu Hata, Altanzul Altaisaikhan, Shu Takakura, Yasunari Asano, Satoshi Izuno, Nobuyuki Sudo, Dietary tryptophan, tyrosine, and phenylalanine depletion induce reduced food intake and behavioral alterations in mice., Physiology & behavior, 10.1016/j.physbeh.2021.113653, 244, 113653-113653, 2022.02, Important precursors of monoaminergic neurotransmitters, dietary tryptophan (TRP), tyrosine, and phenylalanine (all referred to as TTP), play crucial roles in a wide range of behavioral and emotional functions. In the current study, we investigated whether diets devoid of TTP or diets deficient in TRP alone can affect body weight, behavioral characteristics, and gut microbiota, by comparing mice fed on these amino acids-depleted diets to mice fed on diets containing regular levels of amino acids. Both dietary TTP- and TRP-deprived animals showed a reduction in food intake and body weight. In behavioral analyses, the mice fed TTP-deprived diets were more active than mice fed diets containing regular levels of amino acids. The TRP-deprived group exhibited a reduction in serum TRP levels, concomitant with a decrease in serotonin and 5-hydroxyindoleacetic acid levels in some regions of the brain. The TTP-deprived group showed a reduction in TTP levels in the serum, concomitant with decreases in both phenylalanine and tyrosine levels in the hippocampus, as well as serotonin, norepinephrine, and dopamine concentrations in some regions of the brain. Regarding the effects of TRP or TTP deprivation on gut microbial ecology, the relative abundance of genus Roseburia was significantly reduced in the TTP-deprived group than in the dietary restriction control group. Interestingly, TTP was found even in the feces of mice fed TTP- and TRP-deficient diets, suggesting that TTP is produced by microbial or enzymatic digestion of the host-derived proteins. However, microbe generated TTP did not compensate for the systemic TTP deficiency induced by the lack of dietary TTP intake. Collectively, these results indicate that chronic dietary TTP deprivation induces decreased monoamines and their metabolites in a brain region-specific manner. The altered activities of the monoaminergic systems may contribute to increased locomotor activity.. |
| 6. |
Satoshi Izuno, Kazufumi Yoshihara, Nobuyuki Sudo, Role of Gut Microbiota in the Pathophysiology of Stress-Related Disorders: Evidence from Neuroimaging Studies., Annals of nutrition & metabolism, 10.1159/000517420, 77 Suppl 2, 4-10, 2021.07, BACKGROUND: The brain and gut communicate bidirectionally via immune, neurological, and endocrine pathways, which is termed the "brain-gut interaction." Recent studies of gut microbiota as a mediator of this interaction have provided a growing body of scientific evidence that suggests that the gut microbiota influences stress and emotional responses and stress-related disorders. SUMMARY: Major advances in analytical methods have led to an increased number of studies that combine gut microbiota and neuroimaging, mainly magnetic resonance imaging, to elucidate the mechanisms. Observational studies have been done to examine brain characteristics related to gut microbiota profiles, and intervention studies have examined brain changes related to probiotic intake. Studies of healthy subjects using negative emotional stimuli have shown that the pattern of emotional response differs depending on the gut microbiota profile and that probiotic intervention can modulate emotional response and be a buffer against the negative effects of stress. In studies on irritable bowel syndrome (IBS), a typical psychosomatic disorder, IBS-specific gut microbiota were reported to contribute to visceral irritability and pain by affecting the subcortical regions. Studies on psychiatric disorders revealed that a relative abundance of Bacteroides that produce γ-aminobutyric acid in feces was associated with a change in brain function specific to depression and that gut microbiota have an influence on abnormalities in the reward system of attention-deficit/hyperactivity disorder.. |
| 7. |
Sayo Hamatani, Yoshiyuki Hirano, Ayako Sugawara, Masanori Isobe, Naoki Kodama, Kazufumi Yoshihara, Yoshiya Moriguchi, Tetsuya Ando, Yuka Endo, Jumpei Takahashi, Nobuhiro Nohara, Tsunehiko Takamura, Hiroaki Hori, Tomomi Noda, Keima Tose, Keita Watanabe, Hiroaki Adachi, Motoharu Gondo, Shu Takakura, Shin Fukudo, Eiji Shimizu, Kazuhiro Yoshiuchi, Yasuhiro Sato, Atsushi Sekiguchi, Eating Disorder Neuroimaging Initiative (EDNI): a multicentre prospective cohort study protocol for elucidating the neural effects of cognitive-behavioural therapy for eating disorders., BMJ open, 10.1136/bmjopen-2020-042685, 11, 1, e042685, 2021.01, INTRODUCTION: Anorexia nervosa is a refractory psychiatric disorder with a mortality rate of 5.9% and standardised mortality ratio of 5.35, which is much higher than other psychiatric disorders. The standardised mortality ratio of bulimia nervosa is 1.49; however, it is characterised by suicidality resulting in a shorter time to death. While there is no current validated drug treatment for eating disorders in Japan, cognitive-behavioural therapy (CBT) is a well-established and commonly used treatment. CBT is also recommended in the Japanese Guidelines for the Treatment of Eating Disorders (2012) and has been covered by insurance since 2018. However, the neural mechanisms responsible for the effect of CBT have not been elucidated, and the use of biomarkers such as neuroimaging data would be beneficial. METHODS AND ANALYSIS: The Eating Disorder Neuroimaging Initiative is a multisite prospective cohort study. We will longitudinally collect data from 72 patients with eating disorders (anorexia nervosa and bulimia nervosa) and 70 controls. Data will be collected at baseline, after 21-41 sessions of CBT and 12 months later. We will assess longitudinal changes in neural circuit function, clinical data, gene expression and psychological measures by therapeutic intervention and analyse the relationship among them using machine learning methods. ETHICS AND DISSEMINATION: The study was approved by The Ethical Committee of the National Center of Neurology and Psychiatry (A2019-072). We will obtain written informed consent from all patients who participate in the study after they had been fully informed about the study protocol. All imaging, demographic and clinical data are shared between the participating sites and will be made publicly available in 2024. TRIAL REGISTRATION NUMBER: UMIN000039841.. |
| 8. |
Noriyuki Miyata, Tomokazu Hata, Shu Takakura, Kazufumi Yoshihara, Chihiro Morita, Katsunaka Mikami, Koji Nomoto, Kouji Miyazaki, Hirokazu Tsuji, Nobuyuki Sudo, Metabolomics profile of Japanese female patients with restricting-type anorexia nervosa., Physiology & behavior, 10.1016/j.physbeh.2020.113204, 228, 113204-113204, 2020.10, In this study, the serum metabolic profiles of 10 female patients with restricting type anorexia nervosa (ANR) were compared to those of 10 age-matched healthy female controls. While the levels of amino acids were lower among the patients than among the controls, the levels of uremic toxins, including p-cresyl sulfate (PCS), indole-3-acetic acid, and phenyl sulfate, were higher in ANR patients. The serum PCS levels correlated positively with the abundance of the Clostridium coccoides group or the C. leptum subgroup in the feces of patients, but not in those of controls. Collectively, these results indicate that the serum metabolic profiles of patients with ANR differ from those of healthy women in terms of both decreased amino acid levels and increased uremic toxins. Gut microbes including C. coccoides or C. leptum may be involved in such an increase in uremic toxins.. |
| 9. |
Relations among Personality, Coping, and Subjective Stress Using Covariance Structure Analysis : Analyses of Gender Differences
Background : As well as lifestyle habits such as smoking, diet, sleep and physical activity, coping strategies against psychological stress can be important factors which explain the relationship between personality and diseases. The aim of this study was to investigate the relations among personality, coping strategies, lifestyle habits, and subjective stress. Method : Based on self-administered questionnaire obtained from 11,552 participants in the Kyushu University Fukuoka Cohort Study, we executed covariance structure analysis. Results : Higher neuroticism was associated with more frequent passive coping strategies and less frequent positive coping strategies in both men and women. On the other hand, when treating extraversion as an exogenous variable, difference was seen between men and women as to more effective coping. Conclusion : It was suggested that personality traits affect psychological stress via not only lifestyle habits, but also coping strategies. . |
| 10. |
Tae Kimura-Todani, Tomokazu Hata, Noriyuki Miyata, Shu Takakura, Kazufumi Yoshihara, Xue-Ting Zhang, Yasunari Asano, Altanzul Altaisaikhan, Takamitsu Tsukahara, Nobuyuki Sudo, Dietary delivery of acetate to the colon using acylated starches as a carrier exerts anxiolytic effects in mice, PHYSIOLOGY & BEHAVIOR, 10.1016/j.physbeh.2020.113004, 223, 113004-113004, 2020.09, Recently, short-chain fatty acids (SCFA) have been shown to play an important role in mediating the gut-brain interaction and thereby participate in the patho-physiological process of stress-related disorders. In the current study, we examined whether SCFA generated in the lower gut affects host metabolic and behavioral characteristics. To determine this, we used special diets containing acylated starches that can reach the colon without being absorbed in the upper gastrointestinal tract of male mice. The delivery of SCFA to the colon using this method induced a substantial increase in acetate, butyrate, and propionate in the cecum. Moreover, the diets containing acylated starches also decreased microbial diversity in the cecum, concomitant with a significant impact on microbial composition. In marble-burying (MB) tests, the mice that consumed diets containing acetylated starches showed a decrease in anxiety-like behavior compared with the mice that consumed diets containing either butyrylated or propionylated starches. Cecal acetate contents were significantly associated with anxiety-like behaviors when evaluated by elevated plus-maze and MB tests. Collectively, these results indicate that gut acetate elevation of a dietary origin may exert anxiolytic effects on behavioral phenotypes of the host.. |
| 11. |
Tomokazu Hata, Noriyuki Miyata, Shu Takakura, Kazufumi Yoshihara, Yasunari Asano, Tae Kimura-Todani, Makoto Yamashita, Xue-Ting Zhang, Natsuru Watanabe, Katsunaka Mikami, Yasuhiro Koga, Nobuyuki Sudo, The Gut Microbiome Derived From Anorexia Nervosa Patients Impairs Weight Gain and Behavioral Performance in Female Mice, ENDOCRINOLOGY, 10.1210/en.2019-00408, 160, 10, 2441-2452, 2019.10, Anorexia nervosa (AN) results in gut dysbiosis, but whether the dysbiosis contributes to AN-specific pathologies such as poor weight gain and neuropsychiatric abnormalities remains unclear. To address this, germ-free mice were reconstituted with the microbiota of four patients with restricting-type AN (gAN mice) and four healthy control individuals (gHC mice). The effects of gut microbes on weight gain and behavioral characteristics were examined. Fecal microbial profiles in recipient gnotobiotic mice were clustered with those of the human donors. Compared with gHC mice, gAN mice showed a decrease in body weight gain, concomitant with reduced food intake. Food efficiency ratio (body weight gain/food intake) was also significantly lower in gAN mice than in gHC mice, suggesting that decreased appetite as well as the capacity to convert ingested food to unit of body substance may contribute to poor weight gain. Both anxiety-related behavior measured by open-field tests and compulsive behavior measured by a marble-burying test were increased only in gAN mice but not in gHC mice. Serotonin levels in the brain stem of gAN mice were lower than those in the brain stem of gHC mice. Moreover, the genus Bacteroides showed the highest correlation with the number of buried marbles among all genera identified. Administration of Bacteroides vulgatus reversed compulsive behavior but failed to exert any substantial effect on body weight. Collectively, these results indicate that AN-specific dysbiosis may contribute to both poor weight gain and mental disorders in patients with AN.. |
| 12. |
Takahiko Koike, Hiroki C. Tanabe, Saori Adachi-Abe, Shuntaro Okazaki, Eri Nakagawa, Akihiro T. Sasaki, Koji Shimada, Sho K. Sugawara, Haruka K. Takahashi, Kazufumi Yoshihara, Norihiro Sadato, Role of the right anterior insular cortex in joint attention-related identification with a partner, SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE, 10.1093/scan/nsz087, 14, 10, 1131-1145, 2019.10, Understanding others as intentional agents is critical in social interactions. We perceive others' intentions through identification, a categorical judgment that others should work like oneself. The most primitive form of understanding others' intentions is joint attention (JA). During JA, an initiator selects a shared object through gaze (initiative joint attention, IJA), and the responder follows the direction of the initiator's gaze (reactive joint attention, RJA). Therefore, both participants share the intention of object selection. However, the neural underpinning of shared intention through JA remains unknown. In this study, we hypothesized that JA is represented by inter-individual neural synchronization of the intention-related activity. Additionally, JA requires eye contact that activates the limbic mirror system; therefore, we hypothesized that this system is involved in shared attention through JA. To test these hypotheses, participants underwent hyperscanning fMRI while performing JA tasks. We found that IJA-related activation of the right anterior insular cortex of participants was positively correlated with RJA-related activation of homologous regions in their partners. This area was activated by volitional selection of the target during IJA. Therefore, identification with others by JA is likely accomplished by the shared intentionality of target selection represented by inter-individual synchronization of the right anterior insular cortex.. |
| 13. |
Tomokazu Furukawa, Hiroshi Nakano, Kazufumi Yoshihara, Nobuyuki Sudo, Predictors of objectively measured snoring in a working population, SLEEP AND BIOLOGICAL RHYTHMS, 10.1007/s41105-019-00220-5, 17, 3, 349-354, 2019.07, Although there have been many epidemiological studies of snoring, most did not assess snoring objectively. The aim of this study was to identify predictive factors for snoring measured objectively in a working population in Japan. We used IC recorders for the overnight tracheal sound monitoring of 191 employees of two facilities for two nights. Snoring was characterized by two variables: snoring time (%ST) as a percentage of recording time, and the mean tracheal sound energy during recording time (Leq, the equivalent sound pressure level). After excluding those with insufficient data, 172 subjects were included in the final analysis [124 men; age, 44.3 +/- 9.9 years; body mass index (BMI), 22.9 +/- 3.7kg/m(2)]. Relationships between the two snoring variables and age, sex, BMI, drinking, smoking, and night nasal congestion were evaluated, and the predictors of snoring were identified using multiple regression analysis with %ST and Leq as the dependent variables. The mean values of %ST and Leq were 7.4 +/- 7.4% and 102.1 +/- 5.2 dB, respectively. Multiple regression analysis revealed that BMI (p |
| 14. |
The effect of escitalopram on the somatic symptoms of patients with stress-related disorders. |
| 15. |
Tomokazu Hata, Yasunari Asano, Kazufumi Yoshihara, Tae Kimura-Todani, Noriyuki Miyata, Xue-Ting Zhang, Shu Takakura, Yuji Aiba, Yasuhiro Koga, Nobuyuki Sudo, Regulation of gut luminal serotonin by commensal microbiota in mice, PLOS ONE, 10.1371/journal.pone.0180745, 12, 7, e0180745, 2017.07, Gut lumen serotonin (5-hydroxytryptamine: 5-HT) contributes to several gastrointestinal functions such as peristaltic reflexes. 5-HT is released from enterochromaffin (EC) cells in response to a number of stimuli, including signals from the gut microbiota. However, the specific mechanism by which the gut microbiota regulates 5-HT levels in the gut lumen has not yet been clarified. Our previous work with gnotobiotic mice showed that free catecholamines can be produced by the deconjugation of conjugated catecholamines; hence, we speculated that deconjugation by bacterial enzymes may be one of the mechanisms whereby gut microbes can produce free 5-HT in the gut lumen. In this study, we tested this hypothesis using germ-free (GF) mice and gnotobiotic mice recolonized with specific pathogen-free (SPF) fecal flora (EX-GF). The 5-HT levels in the lumens of the cecum and colon were significantly lower in the GF mice than in the EX-GF mice. Moreover, these levels were rapidly increased, within only 3 days after exposure to SPF microbiota. The majority of 5-HT was in an unconjugated, free form in the EX-GF mice, whereas approximately 50% of the 5-HT was found in the conjugated form in the GF mice. These results further support the current view that the gut microbiota plays a crucial role in promoting the production of biologically active, free 5-HT. The deconjugation of glucuronide-conjugated 5-HT by bacterial enzymes is likely one of the mechanisms contributing to free 5-HT production in the gut lumen.. |
| 16. |
Tetsuya Hiramoto, Kazufumi Yoshihara, Yasunari Asano, Nobuyuki Sudo, Protective Role of the Hepatic Vagus Nerve against Liver Metastasis in Mice, NEUROIMMUNOMODULATION, 10.1159/000487483, 24, 6, 341-347, 2017.04, Objective(s): Although accumulating evidence has shown that the autonomic nervous system is involved in liver pathology, its role in regulating cancer development remains unclear. The purpose of this study was to elucidate its detailed mechanisms. Methods: A mouse model of liver metastasis of colorectal cancer was used. To elucidate the potential mechanisms involved, we examined the effect of selective hepatic vagotomy on the survival rate and liver-to-body weight. We further evaluated the possible involvement of the hepatic sympathetic nerve fibers in this model. Results: The mortality rate and the liver-to-body weight ratio after cancer inoculation were significantly higher in the vagotomized mice than in the sham-operated mice. The vagotomized mice exhibited a transient decrease in hepatic norepinephrine levels following cancer inoculation. Interestingly, the vagotomy-induced exacerbation of liver metastasis was attenuated by supplementary norepinephrine or phenylephrine, a selective alpha(1)-adrenoceptor agonist, but not by clonidine, a selective alpha(2)-adrenoceptor agonist. Conclusion: Collectively, these results suggest that the hepatic vagus nerve may play a protective role against liver metastasis. Hepatic sympathetic nerves may also be involved as a protective efferent loop, possibly acting through the alpha(1-)adrenoceptor. (C) 2018 S. Karger AG, Basel. |
| 17. |
Michelle G. Rooks, Patrick Veiga, Analise Z. Reeves, Sydney Lavoie, Koji Yasuda, Yasunari Asano, Kazufumi Yoshihara, Monia Michaud, Leslie Wardwell-Scott, Carey Ann Gallini, Jonathan N. Glickman, Nobuyuki Sudo, Curtis Huttenhower, Cammie F. Lesser, Wendy S. Garrett, QseC inhibition as an antivirulence approach for colitis-associated bacteria, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 10.1073/pnas.1612836114, 114, 1, 142-147, 2017.01, Hosts and their microbes have established a sophisticated communication system over many millennia. Within mammalian hosts, this dynamic cross-talk is essential for maintaining intestinal homeostasis. In a genetically susceptible host, dysbiosis of the gut microbiome and dysregulated immune responses are central to the development of inflammatory bowel disease (IBD). Previous surveys of stool from the T-bet(-/-)Rag2(-/-) IBD mouse model revealed microbial features that discriminate between health and disease states. Enterobacteriaceae expansion and increased gene abundances for benzoate degradation, two-component systems, and bacterial motility proteins pointed to the potential involvement of a catecholamine-mediated bacterial signaling axis in colitis pathogenesis. Enterobacteriaceae sense and respond tomicrobiota-generated signals and host-derived catecholamines through the two-component quorum-sensing Escherichia coli regulators B and C (QseBC) system. On signal detection, QseC activates a cascade to induce virulence gene expression. Although a single pathogen has not been identified as a causative agent in IBD, adherent-invasive Escherichia coli (AIEC) have been implicated. Flagellar expression is necessary for the IBD-associated AIEC strain LF82 to establish colonization. Thus, we hypothesized that qseC inactivation could reduce LF82's virulence, and found that an absence of qseC leads to down-regulated flagellar expression and motility in vitro and reduced colonization in vivo. We extend these findings on the potential of QseC-based IBD therapeutics to three preclinical IBD models, wherein we observe that QseC blockade can effectively modulate colitogenic microbiotas to reduce intestinal inflammation. Collectively, our data support a role for QseC-mediated bacterial signaling in IBD pathogenesis and indicate that QseC inhibition may be a useful microbiota-targeted approach for disease management.. |
| 18. |
Tomokazu Furukawa, Hiroshi Nakano, Kazufumi Yoshihara, Nobuyuki Sudo, The Relationship between Snoring Sound Intensity and Morning Blood Pressure in Workers, JOURNAL OF CLINICAL SLEEP MEDICINE, 10.5664/jcsm.6340, 12, 12, 1601-1606, 2016.12, Study Objectives: This study aimed to determine the consequences of snoring independent of obstructive sleep apnea (OSA) and hypothesized that snoring sound intensity, as assessed by mean tracheal sound (TS) energy (Leq), is related to morning blood pressure (BP).Methods: A home-based TS monitoring study was performed for two nights on 191 workers in Japan using an IC recorder. Leq and the respiratory disturbance index (RDI) were calculated from the TS data. RDI was used as a marker of OSA severity. Systolic and diastolic BP measurements in the evening and morning (eSBP/eDBP and mSBP/mDBP, respectively) were done before and after TS recording. The data of the second night were analyzed.Results: Leq was significantly related to both mSBP and mDBP (r = 0.32, p |
| 19. |
Naoki Hirabayashi, Jun Hata, Tomoyuki Ohara, Naoko Mukai, Masaharu Nagata, Mao Shibata, Seiji Gotoh, Yoshihiko Furuta, Fumio Yamashita, Kazufumi Yoshihara, Takanari Kitazono, Nobuyuki Sudo, Yutaka Kiyohara, Toshiharu Ninomiya, Association Between Diabetes and Hippocampal Atrophy in Elderly Japanese: The Hisayama Study, DIABETES CARE, 10.2337/dc15-2800, 39, 9, 1543-1549, 2016.09, OBJECTIVETo investigate the association between diabetes and brain or hippocampal atrophy in an elderly population.RESEARCH DESIGN AND METHODSA total of 1,238 community-dwelling Japanese subjects aged >= 65 years underwent brain MRI scans and a comprehensive health examination in 2012. Total brain volume (TBV), intracranial volume (ICV), and hippocampal volume (HV) were measured using MRI scans for each subject. We examined the associations between diabetes-related parameters and the ratios of TBV to ICV (an indicator of global brain atrophy), HV to ICV (an indicator of hippocampal atrophy), and HV to TBV (an indicator of hippocampal atrophy beyond global brain atrophy) after adjustment for other potential confounders.RESULTSThe multivariable-adjusted mean values of the TBV-to-ICV, HV-to-ICV, and HV-to-TBV ratios were significantly lower in the subjects with diabetes compared with those without diabetes (77.6% vs. 78.2% for the TBV-to-ICV ratio, 0.513% vs. 0.529% for the HV-to-ICV ratio, and 0.660% vs. 0.676% for the HV-to-TBV ratio; all P |
| 20. |
Masahiro Matsunaga, Hiroaki Kawamichi, Takahiko Koike, Kazufumi Yoshihara, Yumiko Yoshida, Haruka K. Takahashi, Eri Nakagawa, Norihiro Sadato, Structural and functional associations of the rostral anterior cingulate cortex with subjective happiness, NEUROIMAGE, 10.1016/j.neuroimage.2016.04.020, 134, 132-141, 2016.07, Happiness is one of the most fundamental human goals, which has led researchers to examine the source of individual happiness. Happiness has usually been discussed regarding two aspects (a temporary positive emotion and a trait-like long-term sense of being happy) that are interrelated; for example, individuals with a high level of trait-like subjective happiness tend to rate events as more pleasant. In this study, we hypothesized that the interaction between the two aspects of happiness could be explained by the interaction between structure and function in certain brain regions. Thus, we first assessed the association between gray matter density (GMD) of healthy participants and trait-like subjective happiness using voxel-based morphometry (VBM). Further, to assess the association between the GMD and brain function, we conducted functional magnetic resonance imaging (MRI) using the task of positive emotion induction (imagination of several emotional life events). VBM indicated that the subjective happiness was positively correlated with the GMD of the rostral anterior cingulate cortex (rACC). Functional MRI demonstrated that experimentally induced temporal happy feelings were positively correlated with subjective happiness level and rACC activity. The rACC response to positive events was also positively correlated with its GMD. These results provide convergent structural and functional evidence that the rACC is related to happiness and suggest that the interaction between structure and function in the rACC may explain the trait-state interaction in happiness. (C) 2016 Elsevier Inc. All rights reserved.. |
| 21. |
Kazufumi Yoshihara, Hiroki C. Tanabe, Hiroaki Kawamichi, Takahiko Koike, Mika Yamazaki, Nobuyuki Sudo, Norihiro Sadato, 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, Activation of the sympathetic nervous systemis essential for coping with environmental stressors such as fearful stimuli. Recent human imaging studies demonstrated that activity in some cortical regions, such as the anterior cingulate cortex (ACC) and anterior insula cortex (aIC), is related to sympathetic activity. However, little is known about the functional brain connectivity related to sympathetic response to fearful stimuli. The participants were 32 healthy, right-handed volunteers. Functional magnetic resonance imaging (fMRI) was used to examine brain activity when watching horror and control movies. Fingertip temperature was taken during the scanning as a measure of sympathetic response. The movies were watched a second time, and the degree of fear (9-point Likert-type scale) was evaluated every three seconds. The brain activity of the ACC, bilateral aIC, and bilateral anterior prefrontal cortex (aPFC) was correlated with the change rate of fingertip temperature, with or without fearful stimuli. Functional connectivity analysis revealed significantly greater positive functional connectivity between the amygdala and the ACC and between the amygdala and the aIC when watching the horror movie than when watching the control movie. Whole-brain psycho-physiological interaction (PPI) analysis revealed that the functional connectivity between the left amygdala and the ACC was modulated according to the fear rating. Our results indicate that the increased functional connectivity between the left amygdala and the ACC represents a sympathetic response to fearful stimuli. (C) 2016 The Authors. Published by Elsevier Inc.. |
| 22. |
Hiroaki Kawamichi, Kazufumi Yoshihara, Sho K. Sugawara, Masahiro Matsunaga, Kai Makita, Yuki H. Hamano, Hiroki C. Tanabe, Norihiro Sadato, 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, Helping behavior is motivated by empathic concern for others in distress. Although empathic concern is pervasive in daily life, its neural mechanisms remain unclear. Empathic concern involves the suppression of the emotional response to others' distress, which occurs when individuals distance themselves emotionally from the distressed individual. We hypothesized that helping behavior induced by empathic concern, accompanied by perspective-taking, would attenuate the neural activation representing aversive feelings. We also predicted reward system activation due to the positive feeling resulting from helping behavior. Participant underwent functional magnetic resonance imaging while playing a virtual ball-toss game. In some blocks ("concern condition"), one player ("isolated player") did not receive ball-tosses from other players. In this condition, participants increased ball-tosses to the isolated player (helping behavior). Participants then evaluated the improved enjoyment of the isolated player resulting from their helping behavior. Anterior cingulate activation during the concern condition was attenuated by the evaluation of the effect of helping behavior. The right temporoparietal junction, which is involved in perspective-taking and the dorsal striatum, part of the reward system, were also activated during the concern condition. These results suggest that humans can attenuate affective arousal by anticipating the positive outcome of empathic concern through perspective-taking.. |
| 23. |
Takahiko Koike, Hiroki C. Tanabe, Shuntaro Okazaki, Eri Nakagawa, Akihiro T. Sasaki, Koji Shimada, Sho K. Sugawara, Haruka K. Takahashi, Kazufumi Yoshihara, Jorge Bosch-Bayard, Norihiro Sadatoa, Neural substrates of shared attention as social memory: A hyperscanning functional magnetic resonance imaging study, NEUROIMAGE, 10.1016/j.neuroimage.2015.09.076, 125, 401-412, 2016.01, During a dyadic social interaction, two individuals can share visual attention through gaze, directed to each other (mutual gaze) or to a third person or an object (joint attention). Shared attention is fundamental to dyadic face-to-face interaction, but how attention is shared, retained, and neutrally represented in a pair-specific manner has not been well studied. Here, we conducted a two-day hyperscanning functional magnetic resonance imaging study in which pairs of participants performed a real-time mutual gaze task followed by a joint attention task on the first day, and mutual gaze tasks several days later. The joint attention task enhanced eye-blink synchronization, which is believed to be a behavioral index of shared attention. When the same participant pairs underwent mutual gaze without joint attention on the second day, enhanced eye-blink synchronization persisted, and this was positively correlated with inter-individual neural synchronization within the right inferior frontal gyrus. Neural synchronization was also positively correlated with enhanced eye-blink synchronization during the previous joint attention task session. Consistent with the Hebbian association hypothesis, the right inferior frontal gyrus had been activated both by initiating and responding to joint attention. These results indicate that shared attention is represented and retained by pair-specific neural synchronization that cannot be reduced to the individual level. (C) 2015 The Authors. Published by Elsevier Inc.. |
| 24. |
Chihiro Morita, Hirokazu Tsuji, Tomokazu Hata, Motoharu Gondo, Shu Takakura, Keisuke Kawai, Kazufumi Yoshihara, Kiyohito Ogata, Koji Nomoto, Kouji Miyazaki, Nobuyuki Sudo, Gut Dysbiosis in Patients with Anorexia Nervosa, PLOS ONE, 10.1371/journal.pone.0145274, 10, 12, e0145274, 2015.12, Anorexia nervosa (AN) is a psychological illness with devastating physical consequences; however, its pathophysiological mechanism remains unclear. Because numerous reports have indicated the importance of gut microbiota in the regulation of weight gain, it is reasonable to speculate that AN patients might have a microbial imbalance, i.e. dysbiosis, in their gut. In this study, we compared the fecal microbiota of female patients with AN (n = 25), including restrictive (ANR, n = 14) and binge-eating (ANBP, n = 11) subtypes, with those of age-matched healthy female controls (n = 21) using the Yakult Intestinal Flora-SCAN based on 16S or 23S rRNA-targeted RT-quantitative PCR technology. AN patients had significantly lower amounts of total bacteria and obligate anaerobes including those from the Clostridium coccoides group, Clostridium leptum subgroup, and Bacteroides fragilis group than the age-matched healthy women. Lower numbers of Streptococcus were also found in the AN group than in the control group. In the analysis based on AN subtypes, the counts of the Bacteroides fragilis group in the ANR and ANBP groups and the counts of the Clostridium coccoides group in the ANR group were significantly lower than those in the control group. The detection rate of the Lactobacillus plantarum subgroup was significantly lower in the AN group than in the control group. The AN group had significantly lower acetic and propionic acid concentrations in the feces than the control group. Moreover, the subtype analysis showed that the fecal concentrations of acetic acid were lower in the ANR group than in the control group. Principal component analysis confirmed a clear difference in the bacterial components between the AN patients and healthy women. Collectively, these results clearly indicate the existence of dysbiosis in the gut of AN patients.. |
| 25. |
Takeharu Chijiwa, Takakazu Oka, Battuvshin Lkhagvasuren, Kazufumi Yoshihara, Nobuyuki Sudo, Prior chronic stress induces persistent polyI:C-induced allodynia and depressive-like behavior in rats: Possible involvement of glucocorticoids and microglia, PHYSIOLOGY & BEHAVIOR, 10.1016/j.physbeh.2015.04.050, 147, 264-273, 2015.08, When animals suffer from viral infections, they develop a set of symptoms known as the "sickness response." Recent studies suggest that psychological stress can modulate the sickness response. However, it remains uncertain whether acute and chronic psychosocial stresses have the same effect on viral infection-induced sickness responses. To address this question, we compared changes in polyI:C-induced sickness responses, such as fever, change of body weight and food intake, mechanical allodynia, and depressive-like behavior, in rats that had been pre-exposed to single and repeated social defeat stresses. Intraperitoneal injection of polyI:C induced a maximal fever of 38.0 degrees C 3 h after injection. Rats exposed to prior social defeat stress exhibited blunted febrile responses, which were more pronounced in the repeated stress group. Furthermore, only the repeated stress group showed late-onset and prolonged mechanical allodynia lasting until 8 days after injection in the von Frey test and prolonged immobility time in the forced swim test 9 days post-injection. To assess the role of glucocorticoids and microglia in the delayed and persistent development of these sickness responses in rats exposed to repeated stress, we investigated the effect of pretreatment with RU486, a glucocorticoid receptor antagonist, and minocycline, an inhibitor of microglial activation, on polyI:C-induced allodynia and depressive-like behavior. Pretreatment with either drug inhibited both the delayed allodynia and depressive-like behavior. The present study demonstrates that repeated, but not single, social defeat stress followed by systemic polyI:C administration induced prolonged allodynia and depressive-like behavior in rats. Our results show that even though a single-event psychosocial stress does not have any effect by itself, animals may develop persistent allodynia and depressive-like behavior when they suffer from an infectious disease if they are pre-exposed to repeated or chronic psychosocial stress. Furthermore, this study suggests that stress-induced corticosterone and microglial activation play a pivotal role in this phenomenon. (C) 2015 Elsevier Inc. All rights reserved.. |
| 26. |
Hiroaki Kawamichi, Ryo Kitada, Kazufumi Yoshihara, Haruka K. Takahashi, Norihiro Sadato, Interpersonal touch suppresses visual processing of aversive stimuli, FRONTIERS IN HUMAN NEUROSCIENCE, 10.3389/fnhum.2015.00164, 9, 164-164, 2015.04, Social contact is essential for survival in human society. A previous study demonstrated that interpersonal contact alleviates pain-related distress by suppressing the activity of its underlying neural network. One explanation for this is that attention is shifted from the cause of distress to interpersonal contact. To test this hypothesis, we conducted a functional MRI (fMRI) study wherein eight pairs of close female friends rated the aversiveness of aversive and non-aversive visual stimuli under two conditions: joining hands either with a rubber model (rubber-hand condition) or with a close friend (humanhand condition). Subsequently, participants rated the overall comfortableness of each condition. The rating result after fMRI indicated that participants experienced greater comfortableness during the human-hand compared to the rubber-hand condition, whereas aversiveness ratings during fMRI were comparable across conditions. The fMRI results showed that the two conditions commonly produced aversive related activation in both sides of the visual cortex (including V1, V2, and V5). An interaction between aversiveness and hand type showed rubber-hand-specific activation for (aversive > non-aversive) in other visual areas (including Vi, V2, V3, and V4v). The effect of interpersonal contact on the processing of aversive stimuli was negatively correlated with the increment of attentional focus to aversiveness measured by a pain-catastrophizing scale. These results suggest that interpersonal touch suppresses the processing of aversive visual stimuli in the occipital cortex. This effect covaried with aversiveness-insensitivity, such that aversive-insensitive individuals might require a lesser degree of attentional capture to aversive-stimulus processing. As joining hands did not influence the subjective ratings of aversiveness, interpersonal touch may operate by redirecting excessive attention away from aversive characteristics of the stimuli.. |
| 27. |
Kazufumi Yoshihara, Psychosomatic treatment for allergic diseases, BIOPSYCHOSOCIAL MEDICINE, 10.1186/s13030-015-0036-2, 9, 8-8, 2015.03, Many reports have been published concerning how psychosocial stress influences the occurrence and progression of allergic diseases such as bronchial asthma and atopic dermatitis. As for asthma, a typical allergic disease often accompanied by psychosomatic related problems, the Global Initiative for Asthma (GINA), international medical guidelines for asthma, describes psychosocial problems as causative factors of poor asthma control and as risk factors for asthma exacerbation, even if symptoms are well controlled. However, because there is little high quality evidence for effective treatments for asthma patients with psychosocial problems, concrete assessments and treatments for such problems is scarcely described in GINA. Therefore, psychosomatic intervention for asthma patients is not effectively conducted on a worldwide scale. In contrast, the "Japanese Guidelines for the Diagnosis and Treatment of Psychosomatic Diseases" describe the assessment and treatment of psychosomatic disorders in detail. In the guidelines, psychosocial factors are classified into five categories; 1) Relation between stress and asthma occurrence or progression, 2) Relation between emotion and asthma symptoms, 3) Problems related to a patient's character and behaviors, 4) Problems of daily life and Quality of Life (QOL), and 5) Problems related to family relationships and life history. The employment of a self-administered questionnaire, the "Psychosomatic Questionnaire related to Asthmatic Occurrence and Progression", is useful for clarifying psychosocial factors and for setting up treatment strategies according to the problems identified. The Japanese guidelines have been proven to be useful, but empirical evidence for their effectiveness is still relatively limited. It will be necessary in the future to accumulate high-quality evidence and to revise the psychosomatic approaches in the guidelines that are universally valid.. |
| 28. |
Hiroaki Kawamichi, Kazufumi Yoshihara, Akihiro T. Sasaki, Sho K. Sugawara, Hiroki C. Tanabe, Ryoji Shinohara, Yuka Sugisawa, Kentaro Tokutake, Yukiko Mochizuki, Tokie Anme, Norihiro Sadato, 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, Although active listening is an influential behavior, which can affect the social responses of others, the neural correlates underlying its perception have remained unclear. Sensing active listening in social interactions is accompanied by an improvement in the recollected impressions of relevant experiences and is thought to arouse positive feelings. We therefore hypothesized that the recognition of active listening activates the reward system, and that the emotional appraisal of experiences that had been subject to active listening would be improved. To test these hypotheses, we conducted functional magnetic resonance imaging (fMRI) on participants viewing assessments of their own personal experiences made by evaluators with or without active listening attitude. Subjects rated evaluators who showed active listening more positively. Furthermore, they rated episodes more positively when they were evaluated by individuals showing active listening. Neural activation in the ventral striatum was enhanced by perceiving active listening, suggesting that this was processed as rewarding. It also activated the right anterior insula, representing positive emotional reappraisal processes. Furthermore, the mentalizing network was activated when participants were being evaluated, irrespective of active listening behavior. Therefore, perceiving active listening appeared to result in positive emotional appraisal and to invoke mental state attribution to the active listener.. |
| 29. |
Ryo Kitada, Kazufumi Yoshihara, Akihiro T. Sasaki, Maho Hashiguchi, Takanori Kochiyama, Norihiro Sadato, 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, The visual perception of others' body parts is critical for understanding and imitating their behavior. The visual cortex in humans includes the extrastriate body area (EBA), which is a large portion of the occipitotemporal cortex that is selectively responsive to visually perceived body parts. Previous neuroimaging studies showed that the EBA not only receives sensory inputs regarding others' body information but also receives kinesthetic feedback regarding one's own actions. This finding raised the possibility that the EBA could be formed via nonvisual sensory modalities. However, the effect of visual deprivation on the formation of the EBA has remained largely unknown. Here, we used fMRI to investigate the effect of vision loss on the development of the EBA. Blind and sighted human subjects performed equally well in a haptic-identification task involving three categories of objects (hand shapes, toy cars, and teapots). The superior part (i.e., the middle temporal gyrus and angular gyrus) of the EBA and the supramarginal gyrus showed greater sensitivity to recognized hand shapes than to inanimate objects, regardless of the sensory modality and visual experience. Unlike the superior part of the EBA, the sensitivity of the inferior part (i.e., the inferior temporal sulcus and middle occipital gyrus) depended on visual experience. However, this vision-dependent sensitivity explained minor individual differences in hand-recognition performance. These results indicate that nonvisual modalities drive the development of the cortical network underlying the recognition of hand gestures with a node in the visual cortex.. |
| 30. |
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, 1-1, 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.. |
| 31. |
Hiroaki Kawamichi, Akihiro T. Sasaki, Masahiro Matsunaga, Kazufumi Yoshihara, Haruka K. Takahashi, Hiroki C. Tanabe, Norihiro Sadato, Medial Prefrontal Cortex Activation Is Commonly Invoked by Reputation of Self and Romantic Partners, PLOS ONE, 10.1371/journal.pone.0074958, 8, 9, e74958, 2013.09, The reputation of others influences partner selection in human cooperative behaviors through verbal reputation representation. Although the way in which humans represent the verbal reputations of others is a pivotal issue for social neuroscience, the neural correlates underlying the representation of verbal reputations of others are unclear. Humans primarily depend on self-evaluation when assessing reputation of self. Likewise, humans might primarily depend on self-evaluation of others when representing their reputation. As interaction promotes the formation of more nuanced, individualized impressions of an interaction partner, humans tend to form self-evaluations of persons with whom they are intimate in their daily life. Thus, we hypothesized that the representation of reputation of others is modulated by intimacy due to one's own evaluation formation of that person. To test this hypothesis, we conducted a functional magnetic resonance imaging experiment with 11 pairs of romantic partners while they viewed an evaluation of a target person (self, partner [intimate other], or stranger [non-intimate other]), made by other evaluators. When compared with strangers, viewing evaluations of self and partner activated overlapping regions in the medial prefrontal cortex. Verbal reputation of self-specific activation was found in the precuneus, which represents self-related processing. The data suggest that midline structures represent reputation of self. In addition, intimacy-modulated activation in the medial prefrontal cortex suggests that the verbal reputation of intimate others is represented similarly to reputation of self. These results suggest that the reputation representation in the medial prefrontal cortex is engaged by verbal reputation of self and intimate others stemming from both own and other evaluators' judgments.. |
| 32. |
Yasunari Asano, Tetsuya Hiramoto, Ryo Nishino, Yuji Aiba, Tae Kimura, Kazufumi Yoshihara, Yasuhiro Koga, Nobuyuki Sudo, Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice, AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 10.1152/ajpgi.00341.2012, 303, 11, G1288-G1295, 2012.12, Asano Y, Hiramoto T, Nishino R, Aiba Y, Kimura T, Yoshihara K, Koga Y, Sudo N. Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am J Physiol Gastrointest Liver Physiol 303: G1288-G1295, 2012. First published October 11, 2012; doi: 10.1152/ajpgi.00341.2012.-There is increasing interest in the bidirectional communication between the mammalian host and prokaryotic cells. Catecholamines (CA), candidate molecules for such communication, are presumed to play an important role in the gut lumen; however, available evidence is limited because of the lack of actual data about luminal CA. This study evaluated luminal CA levels in the gastrointestinal tract and elucidated the involvement of gut microbiota in the generation of luminal CA by comparing the findings among specific pathogen-free mice (SPF-M), germ-free mice (GF-M), and gnotobiotic mice. Substantial levels of free dopamine and norepinephrine were identified in the gut lumen of SPF-M. The free CA levels in the gut lumen were lower in GF-M than in SPF-M. The majority of CA was a biologically active, free form in SPF-M, whereas it was a biologically inactive, conjugated form in GF-M. The association of GF-M with either Clostridium species or SPF fecal flora, both of which have abundant beta-glucuronidase activity, resulted in the drastic elevation of free CA. The inoculation of E. coli strain into GF-M induced a substantial amount of free CA, but the inoculation of its mutant strain deficient in the beta-glucuronidase gene did not. The intraluminal administration of DA increased colonic water absorption in an in vivo ligated loop model of SPF-M, thus suggesting that luminal DA plays a role as a proabsorptive modulator of water transport in the colon. These results indicate that gut microbiota play a critical role in the generation of free CA in the gut lumen.. |
| 33. |
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, 1, 6-6, 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.. |
| 34. |
Tomokazu Furukawa, Hiroshi Nakano, Kenji Hirayama, Tokusei Tanahashi, Kazufumi Yoshihara, Nobuyuki Sudo, Chiharu Kubo, Sankei Nishima, Relationship between snoring sound intensity and daytime blood pressure, SLEEP AND BIOLOGICAL RHYTHMS, 10.1111/j.1479-8425.2010.00455.x, 8, 4, 245-253, 2010.10, We hypothesized that snoring sound intensity may be associated with daytime blood pressure independent of sleep apnea. We aimed to test this hypothesis in a cross-sectional study. The study subjects comprised 515 patients who underwent polysomnography (PSG) for suspected obstructive sleep apnea (OSA) syndrome. Blood pressure was measured in the seated position at rest during the first hospital visit. Snoring sound intensity was assessed by the highest one percentile ambient sound pressure level (L1) while the patient slept during PSG. Of these, 378 patients who had no antihypertensive medication with sufficient data were included in our analysis. We classified the subjects into a non-to-mild OSA group (n = 200; apnea-hypopnea index: AHI = 15). L1 was correlated with both systolic and diastolic blood pressure (r = 0.30 [P |
| 35. |
Tetsuya Hiramoto, Takakazu Oka, Kazufumi Yoshihara, Chiharu Kubo, Pyrogenic Cytokines Did Not Mediate a Stress Interview-Induced Hyperthermic Response in a Patient With Psychogenic Fever: A Case Report, PSYCHOSOMATIC MEDICINE, 10.1097/PSY.0b013e3181bfb02b, 71, 9, 932-936, 2009.11, Objective: To investigate if pyrogenic cytokines mediated psychological stress-induced hyperthermic response in a patient with psychogenic fever. Despite many case reports on psychogenic fever, the mechanism responsible for how psychological stress increases core body temperature (Tc) in humans is not yet known. Case Presentation: A 13-year-old girl with fever (>38 degrees C) of unknown causes was referred to our department because psychogenic fever was suspected. To determine if the fever was actually induced by psychological stress, we conducted a 60-minute stress interview. Her baseline oral temperature was 36.60 degrees C and it began to increase immediately after commencement of the interview, reaching a maximum of 37.42 degrees C 20 minutes after the end of the interview. The plasma level of prostaglandin E-2 and the serum interleukin-6 level were increased 90 minutes after the interview. Serum levels of interleukin-1 alpha, interleukin-1 beta, and macrophage inflammatory protein-1 alpha were all less than their minimum detectable level throughout the observation period. We also measured the patient's thermal preference by immersing her hands in warm (40 degrees C) and cold (20 degrees C) water. Her preference changed from cold to warm only during the increasing phase of oral temperature. Conclusions: This case report shows that a stress interview actually increased Tc in a patient with psychogenic fever. This study suggests that, although pyrogenic cytokines are not involved, the stress interview-induced increase in Tc was an active hyperthermia under the control of the brain, as is infection-induced fever.. |
| 36. |
Kazufumi Yoshihara, Chiharu Kubo, [Psychosomatic disorder and functional somatic syndrome]., Nippon rinsho. Japanese journal of clinical medicine, 67, 9, 1652-1658, 2009.01, Functional somatic syndrome (FSS) has received a great deal of attention in recent years, and most have been treated as psychosomatic disorders. A psychosomatic disorder is a physical disorder that is closely related to psychosocial factors that affect the onset or clinical course of the disease. For most patients with FSS, the mind-body relationship is related to psychosocial stress. It is important to consider the psychosocial background of the patient as it relates to their pathology. Our psychosocial model that includes four psychosocial factors and our five-step treatment program for patients with functional somatic syndromes are presented.. |
| 37. |
Tetsuya Hiramoto, Yoichi Chida, Junko Sonoda, Kazufumi Yoshihara, Nobuyuki Sudo, Chiharu Kubo, The hepatic vagus nerve attenuates Fas-induced apoptosis in the mouse liver via alpha 7 nicotinic acetylcholine receptor, GASTROENTEROLOGY, 10.1053/j.gastro.2008.03.005, 134, 7, 2122-2131, 2008.06, Background & Aims: Although accumulating evidence has recently shown that the efferent vagus nerve attenuates systemic inflammation, it remains unclear whether or not the vagus nerve can affect Fas-induced liver apoptosis. We investigated the effect of the vagus nerve by using a selective hepatic vagotomy. Methods: We assessed the mortality and apoptosis in Fas-induced fulminant hepatitis in sham-operated and vagotomized male C57BL/6 mice. To determine how the nerve influences hepatocyte apoptosis, hepatitis was preceded by pretreatment with nicotine; PNU-282987, an alpha 7 nicotinic acetylchofine receptor (AChR) agonist; liposome-encapsulated dichloromethylene diphosphonate (lipo-Cl(2)MDP), a macrophage eliminator; and Mn (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP), an oxidative inhibitor. Results: Mortality in the vagotomized mice was significantly higher than that in the sham-operated mice following intravenous administration with the anti-Fas antibody Jo-2. This result was also supported by the data from both terminal deoxynucleotidyl-transferase mediated dUTP nick-end labeling and caspase-3 assay, in which vagotomized livers showed a significant elevation in the number of apoptotic hepatocytes and increased caspase-3 activity following Jo-2 treatment compared with the sham-operated livers. Supplementation with nicotine and PNU-282987 dose dependently inhibited this detrimental effect of the vagotomy. Moreover, the vagotomy-triggered exacerbation of Fas-induced hepatitis was completely blocked by lipo-Cl(2)MDP. Similarly, pretreatment with MnTBAP also completely suppressed the vagotomy-triggered exacerbation. Conclusions: The hepatic vagus nerve appears to play an important role in attenuating Fas-induced hepatocyte apoptosis through alpha 7 nicotinic AChR, perhaps by causing the Kupffer cells to reduce their generation of an excessive amount of reactive oxygen species.. |
| 38. |
The effect of aromatherapy on psychological stress resulting from visual stimulus as assessed by electroencephalogram
アロマテラピーは、心身の不調和を改善する効果があることが知られている。そこで、アロマテラピーの効果について検討するために、香り暴露前後において情動視覚刺激ストレスを負荷したときの健常者の脳波を測定した。その結果、香り暴露前ではニュートラルな視覚刺激と比較し、ネガティブな視覚刺激ストレスによって前頭葉においてδ波の振幅が減少し、後頭葉においてδ波、α波、およびβ波の振幅が減少し、左前頭葉から左側頭葉においてγ波の振幅が減少したが、香り暴露後ではこれらの振幅の有意な変化はほとんど認められなかった。今回の調査により、ネガティブな視覚刺激ストレスに対する覚醒度・緊張度の上昇や視覚活動や思考活動の減少がアロマテラピーによって緩和される可能性が示唆された。(著者抄録). |
| 39. |
Sun X, Somada S, Shibata K, Muta H, Yamada H, Yoshihara K, Honda K, Nakamura K, Takayanagi R, Tani K, Podack ER, Yoshikai Y., A critical role of CD30 ligand/CD30 in controlling inflammatory bowel diseases in mice., Gastroenterology., 10.1053/j.gastro.2007.11.004, 134, 2, 447-58, 134:447-58, 2008.02, BACKGROUND & AIMS: A CD30-ligand (CD30L) is a 40-kilodalton, type II membrane-associated glycoprotein belonging to the tumor necrosis factor family. Serum levels of soluble CD30 increased in inflammatory bowel diseases (IBD), suggesting that CD30L/CD30 signaling is involved in the pathogenesis of IBD. In this study, we investigated the role of CD30L in oxazolone (OXA)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis in CD30L knockout (KO) mice. METHODS: Colitis was induced by OXA or TNBS in CD30LKO mice with BALB/c or C57BL/6 background, respectively, and diverse clinical signs of the disease were evaluated. Cytokine production from lamina propria T cells of the colon was assessed by enzyme-linked immunosorbent assay. Anti-interleukin (IL)-4 monoclonal antibody (mAb) or agonistic anti-CD30 mAb was inoculated in mice with colitis induced by OXA or TNBS. RESULTS: CD30LKO mice were susceptible to OXA-induced colitis but resistant to TNBS-induced acute colitis. The levels of T helper cell 2 type cytokines such as IL-4 and IL-13 in the LP T cells were significantly higher, but the levels of interferon gamma were lower in OXA- or TNBS-treated CD30LKO mice than in wild-type mice. In vivo administration of agonistic anti-CD30 mAb ameliorated OXA-induced colitis but aggravated TNBS-induced colitis in CD30LKO mice. CONCLUSIONS: These results suggest that CD30L/CD30 signaling is involved in development of both OXA- and TNBS-induced colitis. Modulation of CD30L/CD30 signaling by mAb could be a novel biologic therapy for IBD.. |
| 40. |
Kazufumi Yoshihara, Hisakata Yamada, Akiko Hori, Toshiki Yajima, Chiharu Kubo, Yasunobu Yoshikai, IL-15 exacerbates collagen-induced an enhanced CD4(+) T cell response arthritis with 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 11 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+ T cells 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.. |
| 41. |
Xun Sun, Hisakata Yamada, Kazufumi Yoshihara, Akira Awaya, Yasunobu Yoshikai, In vivo treatment with a nonapeptide thymic hormone, facteur thymique serique (FTS), ameliorates chronic colitis induced by dextran sulphate sodium in mice, INTERNATIONAL IMMUNOPHARMACOLOGY, 10.1016/j.intimp.2007.02.014, 7, 7, 928-936, 2007.07, Facteur thymique serique (FTS), a thymic hormone with nonapeptide is involved in T cell differentiation in intestine. Here we investigated the effect of FTS on dextran sulphate sodium (DSS)-induced colitis. BALB/c mice were subcutaneously treated with 1 mu g/mouse/day of FTS daily. FTS did not affect the course of acute colitis induced by DSS as assessed by survival rate, clinical activity of diseases, extent of tissue damage of colons. On the other hand, FTS significantly ameliorated chronic colitis induced by multiple cycles of DSS as reflected by lower lethality, weight loss, clinical scores and histological scores. The levels of interferon (IFN)-gamma, interleukin 1(IL-1)-beta, and IL-12p40 in the culture supernatants of lamina propria (LP) cells of colon without any stimulation and IFN-gamma by T cells in the LP T cells under T cell receptor (TCR) triggering were reduced in FTS-treated mice, whereas the levels of IL-10 by LP cells and LPT cells were higher in FTS-treated mice. Thus, FTS may serve to suppress inflammation in DSS-induced chronic colitis accompanied by increased IL-10 production. (c) 2007 Elsevier B.V. All rights reserved.. |
| 42. |
Kazufumi Yoshihara, Chiharu Kubo, Overview of medical treatment and management of chronic fatigue syndrome, Nippon rinsho. Japanese journal of clinical medicine, 65, 6, 1077-1081, 2007.06, A tailor-made management plan that includes various combinations of non-pharmacologic and pharmacologic therapy for patients with chronic fatigue syndrome (CFS) is important. We present an overview of four aspects of our medical treatment and management for CFS: introduction of our medical management system, summary of our management strategy, non-pharmacologic therapy, and pharmacologic therapy; according to foreign guidelines and the latest studies. The main non-pharmacologic therapies for CFS are rehabilitation and lifestyle guidance. Using a graded exercise therapy, we have constructed a broad management strategy for CFS. Herein we introduce our graded exercise therapy. If the symptoms continue despite careful management of the program by the physician, consultation with a psychiatrist or psychosomatic medicine specialist is necessary.. |
| 43. |
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 (phigh 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+ 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 |
| 44. |
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 (Baltimore, Md. : 1950), 176, 1, 507-15, 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.. |
