Tohru Fushiki

Kyoto University, Kioto, Kyōto, Japan

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Publications (256)643.14 Total impact

  • Hanae YAMAZAKI · Tohru FUSHIKI ·
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    ABSTRACT: Kyoto cuisine has a long history and its traditions have been practiced for hundreds of years. In Kyoto, a group of scientists and renowned chefs strives to better understand traditional Kyoto cuisine in order to foster culinary innovation within traditional Kyoto cuisine. We launched a research project in April 2009 using a specially equipped "laboratory-kitchen" located in Kyoto University. Chefs chose a variety of topics related to basic concepts and techniques for cooking. We conducted culinary experimentation, thorough analysis, and diligent discussion on each topic for approximately 6 mo. In the symposium, chefs will present the results of their experiments, discussing their techniques and bringing samples of final products.
    Journal of Nutritional Science and Vitaminology 11/2015; 61(Supplement):S162-S163. DOI:10.3177/jnsv.61.S162 · 0.83 Impact Factor
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    ABSTRACT: β-Klotho (β-Kl), a transmembrane protein expressed in the liver, pancreas, adipose tissues, and brain, is essential for feedback suppression of hepatic bile acid synthesis. Because bile acid is a key regulator of lipid and energy metabolism, we hypothesized potential and tissue-specific roles of β-Kl in regulating plasma lipid levels and body weight. By crossing β-kl(-/-) mice with newly developed hepatocyte-specific β-kl transgenic (Tg) mice, we generated mice expressing β-kl solely in hepatocytes (β-kl(-/-)/Tg). Gene expression, metabolomic, and in vivo flux analyses consistently revealed that plasma level of cholesterol, which is over-excreted into feces as bile acids in β-kl(-/-), is maintained in β-kl(-/-) mice by enhanced de novo cholesterogenesis. No compensatory increase in lipogenesis was observed, despite markedly decreased plasma triglyceride. Along with enhanced bile acid synthesis, these lipid dysregulations in β-kl(-/-) were completely reversed in β-kl(-/-)/Tg mice. In contrast, reduced body weight and resistance to diet-induced obesity in β-kl(-/-) mice were not reversed by hepatocyte-specific restoration of β-Kl expression. We conclude that β-Kl in hepatocytes is necessary and sufficient for lipid homeostasis, whereas nonhepatic β-Kl regulates energy metabolism. We further demonstrate that in a condition with excessive cholesterol disposal, a robust compensatory mechanism maintains cholesterol levels but not triglyceride levels in mice.-Kobayashi, K., Tanaka, T., Okada, S. Morimoto, Y., Matsumura, S., Manio, M. C. C., Inoue, K., Kimura, K., Yagi, T., Saito, Y., Fushiki, T., Inoue, H., Matsumoto, M., Nabeshima, Y.-i. Hepatocyte β-Klotho regulates lipid homeostasis but not body weight in mice.
    The FASEB Journal 10/2015; DOI:10.1096/fj.15-274449 · 5.04 Impact Factor
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    ABSTRACT: High-fat foods tend to be palatable and can cause addiction in mice via a reinforcing effect. However, mice showed preference for low fat concentrations that do not elicit a reinforcing effect in a two-bottle choice test with water as the alternative. This behavior indicates the possibility that the mechanism underlying fat palatability may differ depending on the dietary fat content. To address this issue, we examined the influences of the opioid system and olfactory and gustatory transductions on the intake and reinforcing effects of various concentrations of a dietary fat emulsion (Intralipid). We found that the intake and reinforcing effects of fat emulsion were reduced by the administration of an opioid receptor antagonist (naltrexone). Furthermore, the action of naltrexone was only observed at higher concentrations of fat emulsion. The intake and the reinforcing effects of fat emulsion were also reduced by olfactory and glossopharyngeal nerve transections (designated ONX and GLX, respectively). In contrast to naltrexone, the effects of ONX and GLX were mainly observed at lower concentrations of fat emulsion. These results imply that the opioid system seems to have a greater role in determining the palatability of high-fat foods unlike the contribution of olfactory and glossopharyngeal nerves.
    Journal of Nutritional Science and Vitaminology 08/2015; 61(3):247-54. DOI:10.3177/jnsv.61.247 · 0.83 Impact Factor
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    ABSTRACT: CD36 is a transmembrane protein that is involved in the recognition of certain amphiphilic molecules such as polar lipids in various tissues and body fluids. So far, CD36 homologues in insects have been demonstrated to be present on the surface of olfactory dendrites and to participate in the perception of exogenous compounds. However, little is known about the relationship between CD36 and mammalian olfaction. Indeed, the detection of only CD36 mRNA in the mouse olfactory epithelium has been reported to date. In the present study, to provide potential pieces of evidence for the involvement of CD36 in mammalian olfactory perception, we extensively investigated the localisation of this protein in the mouse olfactory mucosa. In situ hybridisation analysis using antisense oligonucleotides to CD36 mRNA detected aggregated signals within the deeper epithelial layer of olfactory mucosa. The mRNA signals were also detected consistently in the superficial layer of the olfactory epithelium, which is occupied by supporting cells. Immunostaining with an anti-CD36 polyclonal antibody revealed that CD36 localises in the somata and dendrites of distinct olfactory receptor cells and that it occurs abundantly on the olfactory epithelial surface. However, immunoreactive CD36 was rarely detectable in the nerve bundles running in the lamina propria of olfactory mucosa, the axons forming the olfactory nerve layer in the outermost layer of the bulb and axon terminals in the glomeruli. We also obtained electron microscopic evidence for the association of CD36 protein with olfactory cilia. Altogether, we suggest that CD36 plays a role in the mammalian olfaction. In addition, signals for CD36 protein were also detected on or around the microvilli of olfactory supporting cells and the cilia of nasal respiratory epithelium, suggesting a role for this protein other than olfaction in the nasal cavity.
    PLoS ONE 07/2015; 10(7):e0133412. DOI:10.1371/journal.pone.0133412 · 3.23 Impact Factor
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    ABSTRACT: Some neurotrophic factors, which are potent regulators of neuronal development and function, have recently been implicated in the control of energy balance by increasing energy expenditure. We previously identified neudesin as a novel neurotrophic factor with potential roles in the central nervous system. Although neudesin is also expressed in various peripheral tissues including adipose tissue, its physiological roles have not yet been elucidated. We found that neudesin knockout (KO) mice were resistant to high-fat diet-induced obesity and obesity-related metabolic dysfunctions. neudesin KO mice exhibited increased energy expenditure due to increased sympathetic activity, which resulted in increased heat production and fatty acid oxidation in brown adipose tissue and enhanced lipolysis in white adipose tissue. Thus, neudesin, which may be a negative regulator of sympathetic activity, could represent a novel regulator of the development of obesity and obesity-related metabolic dysfunctions.
    Scientific Reports 05/2015; 5:10049. DOI:10.1038/srep10049 · 5.58 Impact Factor

  • Biomedical Research 01/2015; 36(5):303-311. DOI:10.2220/biomedres.36.303 · 1.14 Impact Factor
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    ABSTRACT: We recently reported that G-protein-coupled receptor 120 (GPR120) is expressed on taste buds, and that rodents showed preference for long-chain fatty acids (LCFA) at a low concentration. We also showed that the LCFA (1% linoleic acid) increased the extracellular dopamine (DA) level in the nucleus accumbens (NAc), which participates in reward behavior. However, the mechanism underlying the involvement of the GPR120-agonistic activity of LCFA in the palatability of dietary fat remains elusive. Therefore, we examined the association between the GPR120-agonistic activity and palatability of LCFA. First, we measured Ca(2+) signaling in HEK293 cells stably expressing GPR120 under stimulation by various LCFAs. We then assessed the palatability of the various LCFAs by testing the licking behavior in mice and measured the changes in the NAc-DA level by in vivo microdialysis. Consequently, 14- to 22-carbon unsaturated LCFAs showed strong GPR120-agonistic activity. Additionally, mice displayed high licking response to unsaturated 16- and 18-carbon LCFAs, and unsaturated 18-carbon LCFA significantly increased the DA level. The licking rate and the LCFA-dependent increase in DA level also correlated well with the GPR120- agonistic activity. These findings demonstrate that chemoreception of LCFA by GPR120 is involved in the recognition and palatability of dietary fat.
    Biomedical research (Tokyo, Japan) 12/2014; 35(6):357-67. DOI:10.2220/biomedres.35.357 · 1.10 Impact Factor
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    ABSTRACT: Rodents show a stronger preference for fat than sucrose, even if their diet is isocaloric. This implies that the preference mechanisms for fat and sucrose differ. To compare the contribution of the opioid system to the preference of fat and sucrose, we examined the effects of mu-, delta-, kappa-, and non-selective opioid receptor antagonists on the preference of sucrose and fat, assessed by a two-bottle choice test and a licking test, in mice naïve to sucrose and fat ingestion. Administration of non-selective and mu-selective opioid receptor antagonists more strongly inhibited the preference of fat than sucrose. While the preference of fat was reduced to the same level as water by the antagonist administration that of sucrose was still greater than water. Our results suggest that the preference of fat relies strongly on the opioid system, while that of sucrose is regulated by other mechanisms in addition to the opioid system.
    Bioscience Biotechnology and Biochemistry 12/2014; 79(4):1-6. DOI:10.1080/09168451.2014.991688 · 1.06 Impact Factor
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    ABSTRACT: The opioid system plays an important role in ingestive behavior, especially with regard to palatable high-fat or sweetened foods. In the present study, we investigated the role of the opioid system in the regulation of ingestive behavior in mice with regard to dietary fat intake, reinforcement, and particularly the processes involved in development of these behavior types. Subcutaneous administration of the non-selective opioid receptor antagonist naltrexone (0.5 or 2.0 mg/kg body weight [BW]) reduced the spontaneous intake of fat emulsion (Intralipid). We investigated the effect of naltrexone on reinforcement by using an operant behavioral paradigm under a progressive ratio schedule in which the number of lever presses required to obtain a test sample increased progressively. Mice showed stronger reinforcement by Intralipid as a function of concentration. However, naltrexone (0.5 or 2.0 mg/kg BW) did not affect reinforcement at any concentration of Intralipid in mice that had repeatedly ingested Intralipid before testing was carried out. Intralipid ingestion also induced conditioned place preference (CPP), which is another evaluation index of reinforcement. High-dose naltrexone (2.0 mg/kg BW) administration during CPP conditioning suppressed the reinforcement induced by Intralipid ingestion, although the drug administration (0.5 or 2.0 mg/kg BW) during CPP testing did not affect reinforced behavior. These results suggest that the amount of fat ingestion and reinforcement for fat ingestion are separately regulated by the opioid system. Furthermore, our results indicate that the opioid system plays an important role in acquiring reinforcement for fat but is not required for maintenance of learned reinforcement.
    Physiology & Behavior 11/2014; 138. DOI:10.1016/j.physbeh.2014.11.001 · 2.98 Impact Factor
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    ABSTRACT: Fatty acids (FA) are an important energy source during exercise. In addition to its role as an energy supply for skeletal muscle, FA may activate signaling pathways that regulate gene expression. FA translocase/cluster of differentiation 36 (CD36) and G protein-coupled receptor GPR120 are long-chain FA receptors. In this study, we investigated the impact of CD36 or GPR120 deletion on energy metabolism during exercise. CD36 has been reported to facilitate cellular transport and oxidation of FA during endurance exercise. We show that CD36 deletion decreased exogenous FA oxidation during exercise, using a combination of (13)C-labeled FA oxidation measurement and indirect calorimetry. In contrast, GPR120 deletion had no observable effect on energy metabolism during exercise. Our results further substantiate that CD36-mediated FA transport plays an essential role in efficient FA oxidation during exercise.
    Bioscience Biotechnology and Biochemistry 07/2014; 78(11):1-8. DOI:10.1080/09168451.2014.940835 · 1.06 Impact Factor
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    ABSTRACT: We recently obtained evidence that unsaturated long-chain fatty acids (LCFAs) (e.g. oleic acid) inhibit binding of oxidized low-density lipoproteins (oxLDLs) to CD36. In the present study, we validated this prediction by examining inhibition by unsaturated LCFAs of Alexa-fluor-labeled oxLDL binding to multiwell plates onto which a synthetic CD36 peptide is covalently immobilized via thiol-maleimide coupling.
    Bioscience Biotechnology and Biochemistry 05/2014; 78(5):839-42. DOI:10.1080/09168451.2014.891934 · 1.06 Impact Factor
  • Tohru Fushiki ·
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    ABSTRACT: Potential mechanisms underlying the high palatability of fat can be assessed by reviewing animal studies on fat detection and brain patterns during reward behavior. Fatty acids are likely recognized by receptors on taste buds, with the signals transmitted to the brain through taste nerves. Ingested oil is broken down and absorbed in the gastrointestinal tract, which also sends signals to the brain through unknown mechanisms. Information from both sensory receptors and peripheral tissue is integrated by the brain, resulting in a strong appetite for fatty foods via a reward system. Understanding mechanisms of fat recognition will prove valuable in the development of strategies to manage the high palatability of foods.
    Bioscience Biotechnology and Biochemistry 03/2014; 78(3):363-9. DOI:10.1080/09168451.2014.905186 · 1.06 Impact Factor
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    ABSTRACT: Body temperature homoeostasis in mammals is governed centrally through the regulation of shivering and non-shivering thermogenesis and cutaneous vasomotion. Non-shivering thermogenesis in brown adipose tissue (BAT) is mediated by sympathetic activation, followed by PGC-1α induction, which drives UCP1. Here we identify nardilysin (Nrd1 and NRDc) as a critical regulator of body temperature homoeostasis. Nrd1(-/-) mice show increased energy expenditure owing to enhanced BAT thermogenesis and hyperactivity. Despite these findings, Nrd1(-/-) mice show hypothermia and cold intolerance that are attributed to the lowered set point of body temperature, poor insulation and impaired cold-induced thermogenesis. Induction of β3-adrenergic receptor, PGC-1α and UCP1 in response to cold is severely impaired in the absence of NRDc. At the molecular level, NRDc and PGC-1α interact and co-localize at the UCP1 enhancer, where NRDc represses PGC-1α activity. These findings reveal a novel nuclear function of NRDc and provide important insights into the mechanism of thermoregulation.
    Nature Communications 02/2014; 5:3224. DOI:10.1038/ncomms4224 · 11.47 Impact Factor
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    ABSTRACT: Transmembrane protein CD36 binds multiple ligands, including oxidized low-density lipoproteins (oxLDLs) and long-chain fatty acids (LCFAs). Our aim was to determine whether LCFAs compete with oxLDLs for binding to CD36. We addressed this issue by examining the inhibitory effect of LCFAs against the binding of Alexa-fluor-labeled oxLDLs (AFL-oxLDL) to a synthetic peptide representing the oxLDL-binding site on CD36 (3S-CD36150-168). All of the unsaturated LCFAs tested, inhibited the binding of AFL-oxLDL to 3S-CD36150-168, albeit to varying degrees. For instance, the concentrations required for 50% inhibition of binding for oleic, linoleic, and α-linolenic acids were 0.25, 0.97, and 1.2 mM, respectively. None of the saturated LCFAs tested (e.g. stearic acid) exhibited inhibitory effects. These results suggest that at least unsaturated LCFAs can compete with oxLDLs for binding to CD36. The study also provides information on the structural requirements of LCFAs for inhibition of oxLDLs-CD36 binding.
    Bioscience Biotechnology and Biochemistry 02/2014; 78(2):238-44. DOI:10.1080/09168451.2014.882750 · 1.06 Impact Factor
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    ABSTRACT: Dried bonito (Katsuobushi) is widely used in Japanese cuisine as a traditional Japanese seasoning. The aroma plays an important role in the flavor of the cuisine. The role of dried bonito aroma was demonstrated in experiments with mice : the aroma of a supercritical carbon dioxide extract of dried bonito stimulated the reward system, consistent with the presentation of highly palatable food. The current research revealed the potent odor-active volatiles of supercritical carbon dioxide dried bonito extract (Bonito CO2 Ex). Aroma extract dilution analysis (AEDA) of Bonito CO2 Ex identified ten odorants as potent odor-active volatiles with the highest flavor dilution (FD) factor of 15 625 and 3 125 : 2-methoxyphenol showed a FD factor of 15 625 , followed by 2-methoxy-5-methylphenol, 2,6-dimethoxyphenol, 4-ethyl-2,6-dimethoxyphenol, 2,6-dimethylphenol, 2-methoxy-4-propylphenol, 4-hydroxy-3-methoxybenzaldehyde, 4-hydroxy-2,5-dimethyl-3(2H)-furanone, (2E,7Z)-trans-4,5-epoxydeca-2,7-dienal and (4Z,7Z)-trideca-4,7-dienal (TDD) with a FD factor of 3 125 . This was the first time TDD was identified in a food. Sensory evaluation of the aroma reconstitutions of Bonito CO2 Ex revealed that TDD contributed significantly to the Bonito CO2 Ex aroma. Furthermore, the efficacy of additional TDD to enhance the pleasant flavor of dried bonito broth was confirmed by sensory evaluation conducted by an experienced chef of traditional Japanese cuisine.
    Nippon Shokuhin Kagaku Kogaku Kaishi 01/2014; 61(11):519-527. DOI:10.3136/nskkk.61.519 · 0.11 Impact Factor
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    ABSTRACT: Japanese cuisine has provided satisfying meals by fully utilizing the characteristic aroma and taste of katsuodashi (dried bonito broth), though it is not rich in sugars or fats. Katsuodashi is a very basic and indispensable element in Japanese cuisine, and is a hot water extract of katsuobushi (dried bonito). It has been reported that a dextrin solution containing natural dried bonito broth has a significant reinforcement effect, and has been suggested that the olfactory stimulation is important for the reinforcement effect. We examined various source materials for broth and identified an optimal method of aroma extraction by two-bottle choice and conditioned place preference tests in mice. By two-bottle choice tests, a solution containing arabushi (a type of katsuobushi) aroma extract obtained by a supercritical CO2 extraction method showed a significantly high preference. The conditioned place preference test showed the dashi-taste solution with arabushi supercritical CO2 extract had a reinforcement effect. Our results suggest that the arabushi extract obtained by supercritical CO2 extraction contains components responsible for preference and reinforcement effects in mice; it could become conducive to making Japanese cuisine more satisfying and palatable.
    Journal of Nutritional Science and Vitaminology 01/2014; 60(5):328-33. DOI:10.3177/jnsv.60.328 · 0.83 Impact Factor
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    ABSTRACT: Changes in the extracellular concentration of dopamine (DA) in the nucleus accumbens (NAc) shell and the basolateral amygdala (BLA) resulting from the voluntary ingestion of either corn oil, mineral oil, or 1% linoleic acid diluted with mineral oil as a vehicle were measured in rats by using in vivo microdialysis after they had been trained to establish a preference for corn oil. Ingesting the mineral oil caused no significant change in DA level in the NAc shell, whereas corn oil ingestion significantly increased the DA level during 0-15 min of the test session, reaching the maximum level of 129.8 ± 6.2% compared with the baseline after 10 min. Ingesting linoleic acid also resulted in a significant increase in DA level during 0-20 min, reaching 125.9 ± 9.0% after 10 min. Similar results were obtained in the BLA. Despite its very low calorie content, a low concentration of non-esterified fatty acid increased the DA levels equivalent to those resulting from corn oil in the brain's reward system.
    Bioscience Biotechnology and Biochemistry 11/2013; 77(11). DOI:10.1271/bbb.130234 · 1.06 Impact Factor
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    ABSTRACT: The present study explored the possibility of generating a novel sensory evaluation instrument for describing comprehensive food palatability via its subdomains (rewarding, cultural, and informational) while keeping physiological factors constant. Seventy-five Japanese participants were asked to taste cheese samples and to respond to a questionnaire that was developed to dissect the distinct subdomains of palatability. The subsequent factor analyses revealed that three major factors may serve as distinct subdomains of palatability: rewarding, cultural, and informational, although the informational factor was not sufficiently robust. Multivariate regression analysis on cheese samples with exactly the same ingredients but sold in different packages led to different comprehensive palatability ratings due to the contribution of the cultural, but not the rewarding, factor. These results suggest that palatability is not merely determined by the physical and chemical properties that are intrinsic to a food product itself, but also depends on psychological properties that can arise through interaction between humans and the food product. The current study presents the first experimental demonstration that palatability could be dissociated to its subdomains.
    Food Science & Nutrition 09/2013; 1(5):369-76. DOI:10.1002/fsn3.48
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    ABSTRACT: The present study explored the possibility that aroma components generated by the oxidation of olive oil may enhance the palatability of olive oil. Using a mouse behavioral model, we found that olive oil oxidized at room temperature for 3 weeks after opening the package, and heated olive oil were both significantly preferred over non-oxidized olive oil. Furthermore, this preference was enhanced with an additive of oxidized refined olive oil flavoring preparation at a certain concentration. These results suggest that the aroma of oxidized fat might be present in most fats, and might act as a signal that makes possible the detection of fats or fatty acid sources.
    Bioscience Biotechnology and Biochemistry 06/2013; 77(6). DOI:10.1271/bbb.120861 · 1.06 Impact Factor
  • Seiya Mochida · Satoshi Tsuzuki · Kuniyo Inouye · Tohru Fushiki ·
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    ABSTRACT: Matriptase is an epithelial-derived type-II transmembrane serine protease. This protease is expressed prominently in the villus tip of small-intestinal epithelia at which senescent cells undergo shedding and/or apoptosis. The basement membrane of epithelial cells, including small-intestinal epithelial cells, contains extracellular matrix (ECM) proteins such as fibronectin and laminin. We found previously that high concentrations of a recombinant matriptase catalytic domain (r-MatCD) (e.g. 1 μM) caused an increased detachment of and increases in the activity of apoptotic effector caspase-3 in a rat small-intestinal epithelial IEC-6 line cultured on laminin-coated plates and proposed that at sites with its high level of expression, matriptase contributes to promoting shedding and/or detachment-induced death of epithelial cells through a mechanism mediating loss of cell-ECM adhesion. In this study, we found that even without increasing cell detachment, a high concentration of r-MatCD causes an increase in caspase-3 activity in IEC-6 cells cultured on fibronectin-coated plates, suggesting that the recombinant matriptase can cause apoptosis by a mechanism unrelated to cell detachment. Also, r-MatCD-treated IEC-6 cells on fibronectin were found to display spindle-like morphological changes. We suggest that r-MatCD causes apoptosis of IEC-6 on fibronectin by a mechanism involving the disruption of cell integrity.
    Cytotechnology 05/2013; 66(3). DOI:10.1007/s10616-013-9582-2 · 1.75 Impact Factor

Publication Stats

6k Citations
643.14 Total Impact Points


  • 1984-2014
    • Kyoto University
      • • Division of Food Science and Biotechnology
      • • Division of Applied Life Sciences
      Kioto, Kyōto, Japan
  • 2010
    • Boca Raton Regional Hospital
      Boca Raton, Florida, United States
  • 2003-2005
    • Hokkaido University
      Sapporo, Hokkaidō, Japan
  • 2001
    • The University of Shiga Prefecture
      • Division of Life Style Studies
      Hikone, Shiga Prefecture, Japan
    • The University of Tokushima
      • School of Medicine
      Tokusima, Tokushima, Japan
  • 1986
    • Nagoya University
      Nagoya, Aichi, Japan