Kazumasa Miki

Toho University, Edo, Tōkyō, Japan

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Publications (303)730.29 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Gastric cancer is the most common cancer in Japan. Genome-wide gene expression in the jejunal pouch mucosa was examined using a DNA microarray and quantitative real-time PCR (qPCR) to evaluate the safety, especially with regard to carcinogenic changes, of the jejunal pouch in patients who showed long-term survival. Biopsy samples of jejunal pouch and jejunal conduit were collected from four patients who had undergone gastrectomy 9 to 13 years previously. Total RNA was extracted, amplified to give complementary RNA, labeled with Cyanine 3-CTP and hybridized with a whole human genome oligo microarray (44k). Gene expression was confirmed partly by qPCR. Although some changes in the expression of 417 reported cancer genes were observed with the DNA microarray, crucial changes related to small intestinal adenocarcinoma were not observed. Changes in the expression of eight genes related to small intestinal adenocarcinoma were also not detected by qPCR. Crucial changes in the expression of genes related to small intestinal adenocarcinoma were not observed in the jejunal pouch of these four patients with gastric cancer by either DNA microarray or qPCR. The present results support the safety of the use of a jejunal pouch with a food pooling function in patients who show long-term survival after gastrectomy.
    Hepato-gastroenterology 01/2012; 59(116):1302-7. · 0.91 Impact Factor
  • Nippon rinsho. Japanese journal of clinical medicine 07/2010; 68 Suppl 7:762-4.
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    ABSTRACT: Intraductal papillary-mucinous neoplasm (IPMN) is an intraductal tumor in which the mucin-producing epithelium shows proliferated papillary and a wide variety of pathological changes ranging from hyperplasia to adenocarcinoma. Therefore, it is important to determine whether an IPMN is benign or malignant. In the present study of patients with IPMN, the protrusion was observed by a peroral pancreatoscopy (PPS) using a small-diameter videoscope and narrow-band imaging (NBI). We carried out the differential diagnosis of benign lesion to malignant lesion. Between April 2003 and May 2009, PPS using a small-diameter videoscope by means of NBI was carried out on 21 hospitalized patients with IPMN (10 cases of adenocarcinoma, 11 cases of adenoma or hyperplasia; 14 males and seven females, with a mean age of 69.4 years). Fifteen focal lesions of the 16 cases in the head of the pancreas (93.7%) and four focal lesions of the five cases in the pancreatic body (80%) were observable, whereas two lesions (adenocarcinoma in the pancreatic body, and adenoma in the uncus of pancreas) were not observable. Endoscopically, seven cases were classified as villous type and two cases as vegetative type, and nine cases were diagnosed as adenocarcinoma. Ten cases with sessile type or semipedunculated type were diagnosed as adenoma or hyperplasia. Vascular patterns and protrusions were detected more clearly in the NBI images than under white light observation. When combined with a videoscope and NBI, pancreatoscopy provided a clear image and was useful for evaluating whether the IPMN was benign or malignant.
    Digestive Endoscopy 04/2010; 22(2):119-23. · 1.61 Impact Factor
  • Kazumasa Miki, Mitsuhiro Fujishiro
    Digestive Endoscopy 05/2009; 21(2):134-5. · 1.61 Impact Factor
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    ABSTRACT: A 62-year-old man was admitted to our hospital complaining of sore throat and epigastralgia. Laboratory tests revealed leukocytosis and an elevated CRP level. CT showed a low density area in the right hypopharynx, wall thickening of the esophageal and gastric wall with an intramural low density area. Phlegmonous esophagogastritis associated with hypopharyngeal abscess was diagnosed. The infection was extension and his condition was serious because of his accompanying poorly controlled diabetes. He was successfully treated by antibiotics and drainage of the hypopharyngeal abscess. CT was useful for early diagnosis, confirmation of the extent of inflammation and follow-up.
    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 04/2009; 106(3):370-6.
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    ABSTRACT: Cancer invasion and metastasis are critical events for patient prognosis; however, the most important step in the whole process of lymph node (LN) metastasis in gastric cancer remains obscure. In this study, the significance of cancer cell behaviors, such as cell detachment, stromal invasion and lymphatic invasion on regional LN metastasis in gastric cancer was investigated by comprehensive immunohistochemistry. A total of 210 cases with gastric cancer were selected. These consisted of 105 cases with regional LN metastasis (LN[+] group) and 105 cases without LN metastasis (LN[-] group). Both groups exhibited the same depth of invasion. Cancer tissues were subjected to immunohistochemistry with antibodies against claudin-3, claudin-4, beta-catenin, matrix metalloproteinase (MMP)-1, and MMP-2, as well as endothelial markers of lymphatic vessel endothelial hyaluronan receptor-1 and von Willebrand factor for the objective discrimination between lymphatics and blood vessels. The expression of each protein as well as the histopathological parameters were compared between LN(+) and LN(-) groups. Along with lymphatic invasion by cancer cells and gross tumor size, MMP-1 expression in cancer cells at the invasive front of the primary tumor was a significant, independent predictor of LN metastasis. The expression of claudins and beta-catenin was associated with the histopathological type of cancer, but not with LN status. Among the cancer invasion-related proteins examined, MMP-1 plays a vital role in LN metastasis of gastric cancer. Tumor size, lymphatic invasion and MMP-1 expression level at the invasive front were the predictive factors of LN metastasis of gastric cancer.
    Journal of Gastroenterology and Hepatology 04/2009; 24(9):1527-33. · 3.33 Impact Factor
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    ABSTRACT: In order to reduce gastric cancer death, mass screening for gastric cancer has been established in Japan for several decades. Only photofluorography is considered to be an acceptable screening method so far, but recent evidence may show the usefulness of serum pepsinogen (PG) measurement for gastric cancer screening. The aim of the present study was to elucidate the feasibility of measuring serum PG levels for detection of gastric cancers. Serum PG levels (PGI/PGII) were measured in asymptomatic middle-aged Japanese between 1991 and 2005. Those with a PGI <or= 70 ng/mL and PGI/PGII <or= 3 were defined as having a positive PG test. According to the obtained results of serum PG levels and previous individual records, those with a positive PG test and those with a negative PG test took gastroendoscopy every 2 and 5 years, respectively. The total number of participating individuals was 101,892 (mean age of 48.7 years). In a total of 21,178 planned gastroendoscopies (20.8%), 13,789 (65.1%) underwent gastroendoscopy and 125 gastric cancers were detected, which corresponded to 0.12% of all participants and to 0.91% of those with gastroendoscopy. Early-stage cancers and intestinal-type intramucosal cancers accounted for 80% and 39% of all the detected cancers, respectively. Serum PG measurement for mass screening of gastric cancer enabled us to achieve high recruitment for gastroendoscopy in intended individuals, a favorable detection rate of gastric cancer and, in particular, an extremely high proportion of early-stage gastric cancer in all the detected cancers.
    Digestive Endoscopy 04/2009; 21(2):78-81. · 1.61 Impact Factor
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    ABSTRACT: Regional lymph node metastasis in gastric cancer is a definitive indicator of the patient's prognosis. The goal of this study was to identify the predictors for lymph node metastasis among all the possible histopathological parameters, especially by conducting an objective discrimination of the lymphatic and blood vessels. A total of 210 resected primary gastric cancers with or without lymph node metastasis were evaluated based on the conventional histopathological parameters together with immunohistochemistry using antisera-recognizing lymphatic endothelial hyaluronan receptor-1 (LYVE-1), von Willebrand factor, and lymphangiogenesis promoter vascular endothelial growth factor-C (VEGF-C) antibodies. A multivariate regression analyses of the results indicated that only lymphatic invasion was a significant independent predictor of lymph node metastasis at any stage of cancer invasion. VEGF-C expression was partially related to lymph node metastasis in early gastric cancer. The identification of lymphatic invasion by LYVE-1 antibody is therefore useful to predict regional lymph node metastasis in gastric cancer.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 01/2009; 454(2):143-51. · 2.56 Impact Factor
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    ABSTRACT: To generate a novel understanding of Intestinal metaplasia (IM) on the basis of cellular differentiation status, a total of 132 gastric surgical specimens were studied using gastric and small intestinal cell markers by much histochemical and Immunohistochemical techniques. The cases were divided into two types: (i) gastric and intestinal (GI) mixed type; and (ii) solely intestinal (I) type, with the reference to the presence of gastric and/or intestinal cell markers. The GI mixed type was subdivided into six subtypes: (i) a subtype consisting of surface mucous (Su), pyloric gland (Py), Intestinal absorptive (Ab), and goblet (Go) cells, but lacking Paneth (Pa) cells, GI(Pa-); (ii) a GI(Pa-) subtype without Py cells, GI(Py-, Pa-); (iii) a GI(Pa-) subtype without Su cells, GI(Su-, Pa-); (iv) a GI(Su-, Pa-) subtype with Pa cells, GI(Su-, Pa+); (v) a Gi(Pa-) subtype with Pa cells, GI(Pa+); and (vi) a GI(Pa+) subtype without Py cells, GI(–, Pa+).The I type was subdivided Into: (I) a subtype consisting of cells with Ab and Go cells, I(Pa-); and (ii) a I(Pa-) subtype with Paneth cells, I(Pa+). The GI mixed subtypes, except for the GI(Py-, Pa-) and GI(Py-, Pa+), were characterized by Intestinalized gastric plts connected with underlying pyloric glands. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) revealed a common prolifemtive cell zone between the two. The GI mixed type, especially the GI(Pa-) subtype, predominated in the pyloric mucose, while the I type was most frequent In the fundle region, suggesting that the pathogenesis of IM differs between these two locations. The results of the study confirm that IM is an abnormal and unstable differentiation status between the stomach and small Intestine.
    Pathology International 12/2008; 47(12):831 - 841. · 1.59 Impact Factor
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    ABSTRACT: Localization of pepsinogens I and II mRNA in the human gastric mucosa was investigated by an in situ hybridization method using digoxigenin labeled cDNA probes. Gastric fundic mucosa from healthy volunteers, which was stained with digoxigenin labeled pepsinogens I and II cDNA probes, showed positive staining in the cytoplasm of both chief cells and mucous neck cells. In contrast, gastric antral mucosa stained with the pepsinogen I cDNA probe showed no positive reaction in the surface mucous cells or pyloric glands. On the other hand, the pyloric glands were stained positively with the pepsinogen II cDNA probe and the staining appeared to be identical to that obtained with the anti pepsinogens I and II monoclonal antibodies using the avidin biotin peroxidase complex technique. These results are consistent with those of previous studies that have employed immunochemical and immunohistochemical techniques. Acta Pathol Jpn 39: 765 771, 1989.
    Pathology International 12/2008; 39(12):765 - 771. · 1.59 Impact Factor
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    ABSTRACT: Volvulus of the large bowel is the third most common cause of colonic obstruction. A patient with colonic obstruction or delayed small intestinal transit may frequently have bacterial overgrowth and increased breath hydrogen (H2) and/or methane (CH4) excretion because the bacterium can contact with food residues for a longer time. A 39 year old woman attended our hospital with complaints of abdominal pain and distension. This patient's abdominal radiograph showed an inverted U-shaped shadow. The fasting breath CH4 level was 26 ppm. An endoscopic procedure was immediately carried out with suspected sigmoid colon volvulus, and detorsion was achieved. There was resolution of the sigmoid volvulus after colonoscopy, and breath CH4 concentration in the next morning decreased to 10 ppm. A liquid meal was supplied at noon on the second hospital day. The breath CH4 concentration increased markedly to 38 ppm at 18:00 although she had no abdominal symptoms. This value peaked at 42 ppm at 18:00 on the third hospital day and was gradually reduced to 20 ppm the next day. The breath H2 concentration value kept a low level during fasting and increased markedly to 51 ppm the next day after a liquid meal was supplied. The next morning, fasting breath H2 concentration rapidly decreased to 6 ppm. This suggests that changes in breath H2 levels may reflect transient malabsorption after a liquid test meal is supplied. In conclusion, breath H2 and CH4 analysis may be another tool for evaluating the intestinal circumstances.
    Journal of Breath Research 09/2008; 2(3):037025. · 2.57 Impact Factor
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    ABSTRACT: The amino acid sequences of three pepsinogens (PG1, PG2 and PG3) of Pacific bluefin tuna (Thunnus orientalis) were deduced by cloning and nucleotide sequencing of the corresponding cDNAs. The amino acid sequences of the pre-forms of PG1, PG2 and PG3 were composed of a signal peptide (16 residues each), a propeptide (41, 37 and 35 residues, respectively) and a pepsin moiety (321, 323 and 332 residues, respectively). Amino acid sequence comparison and phylogenetic analysis indicated that PG1 and PG2 belong to the pepsinogen A family and PG3 to the pepsinogen C family. Homology modeling of the three-dimensional structure suggested that the remarkably high specific activity of PG2 toward hemoglobin, which had been found previously, was partly due to a characteristic deletion of several residues in the S1'-loop region that widens the space of the active site cleft region so as to accommodate protein and larger polypeptide substrates more efficiently. Including the tuna and all other fish pepsinogen sequences available to date, the molecular phylogenetic comparison was made with reference to evolution of fish pepsinogens. It was suggested that functional divergences of pepsinogens (pepsins) occurring in fishes as well as in mammals, correlated with differences in various aspects of fish physiology.
    Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 09/2008; 152(1):9-19. · 1.61 Impact Factor
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    ABSTRACT: The distribution of gas in the digestive tract is easily detected by a plain abdominal radiograph and associated with abdominal symptoms in some dyspeptic patients. Therefore, we investigate whether a gastric bubble detected on the abdominal radiograph is associated with gastroesophageal reflux diseases (GERD) symptoms or not. All of the patients were asked to respond to the F-scale questionnaire regardless of their chief complaints. Plain abdominal films in the erect position were used to classify the form of gastric bubble into four groups: dome-type, irregular-type, stomach-type and undetected-type. The gastric bubble was found in 93.4% of patients on plain films in the erect position. Of them, 55 had a dome-type gastric bubble that indicates the distended fundus and fluid levels. GERD was most frequently detected in the stomach-type group, followed by undetected-type, irregular-type and dome-type. The mean score of the F-scale was significantly higher in stomach-type than in dome-type. It is concluded that a gastric bubble detected on plain abdominal films is an informative marker for evaluating the functional disorder of upper digestive tracts. Physicians have to recognize the importance of plain films of the abdomen in the diagnostic process of GERD.
    Journal of Breath Research 09/2008; 2(3):037024. · 3.59 Impact Factor
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    ABSTRACT: It has been reported that Th2 cytokines down-regulate antitumor immunity, while activation of type 1 T cell responses promotes antitumor immunity. However, detailed information on the immunological background of patients with HCC is still unknown. The objectives of this study were to evaluate the Th1/Th2 balance and to investigate the relation between carcinogenesis and host immunity in patients with chronic hepatitis C, HCV-related liver cirrhosis (LC), or HCC. The study population was 117 patients who had chronic inflammation due to HCV infection diagnosed from pathological examination of liver biopsy specimens, including 32 patients who had HCV-related LC with HCC. Apart from the patients with HCC, they were divided into the four subgroups based on the fibrosis score of Desment (stages 1-4). Blood samples were collected in the early morning before treatment. Flow cytometry was used to assess cytoplasmic IFN-gamma and IL-4 expression by peripheral blood CD4+ T cells, and the percentage of IFN-gamma+ and IL4- T cells (Th1) or IFN-gamma- and IL4+ T cells (Th2) was calculated before the start of each therapy. There were 20 patients in F1, 25 patients in F2, 19 patients in F3, 21 patients in F4, and 32 patients with HCC. In the F4 and HCC groups, Th1 cells tended to increase depending on the extent of fibrosis, although there were no significant differences between these groups and the other groups. In the HCC group, Th2 cells showed a significantly higher percentage than in the F1 or F3 groups. These results suggest that Th1 dominance is lost due to an increase of Th2 cells in HCC patients and that carcinogenesis might occur in patients with chronic HCV infection and increased level of Th2 cells.
    Cancer Chemotherapy and Pharmacology 09/2008; 62(3):401-6. · 2.57 Impact Factor
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    ABSTRACT: Tumor necrosis factor (TNF) induces cancer cell-specific apoptosis by binding to a TNF-related apoptosis-inducing ligand. Binding of the Fas ligand on cytotoxic T lymphocytes to the Fas receptor on hepatocytes is also known to induce apoptosis. The aim of this study was to clarify changes of cytokines in patients with liver cirrhosis (LC) and advanced hepatocellular carcinoma (aHCC) receiving intra-arterial combination chemotherapy. Twenty-one adult Japanese LC patients with aHCC received intra-arterial combination chemotherapy. The serum levels of TNF-alpha, soluble TNF receptor-I (sTNFr-I), soluble Fas ligand (sFas L), and soluble Fas (sFas) were evaluated. Thirteen of the 21 patients (group R) showed an objective response, while the other eight patients (group N) showed no response. The serum level of TNF-alpha was lower after chemotherapy than before chemotherapy in group N, but there was no difference of serum sTNFr-I levels between before and after chemotherapy and there were also no differences between the two groups. The serum sFas levels were higher after chemotherapy than before chemotherapy in group N, while there was no difference among groups. These results indicate that a high serum TNF-alpha level and a low serum sFas level might be important for successful combined arterial chemotherapy in LC patients with aHCC.
    Cancer Chemotherapy and Pharmacology 08/2008; 62(2):271-6. · 2.57 Impact Factor
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    ABSTRACT: The changes with development in the expression of cathepsin E in the fetal rat stomach were examined immunochemically and immunohistochemically. The activity of acid proteinase in fetal gastric extracts increased dramatically during late gestational stages, rising from 0.017 units per mg of protein on day 15 of gestation to 0.591 units per mg of protein on day 21 of gestation. Electrophoretic analysis, combined with immunological tests, showed that the increase was due exclusively to increases in the activity of the monomeric and dimeric forms of cathepsin E, while SDS-PAGE-immunoblot analysis revealed that both forms are present as a 43-kDa proenzyme. Immunohistochemically, cathepsin E was localized in the cytoplasm of all proliferating epithelial cells of pars glandularis on day 16 of gestation or later. As revealed by conventional histological methods, surface mucous cells and parietal cells appeared for the first time in specimens on day 19 of gestation, and all of these cells were immunopositive for cathepsin E. The present study further indicated that cathepsin E is the predominant aspartic proteinase in the stomach of young rats, until pepsinogen C appears. Based on these results, possible roles of gastric cathepsin E are discussed.
    Embryologia 07/2008; 35(3):349 - 356. · 2.18 Impact Factor
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    ABSTRACT: It has been reported that Th2 cytokines down-regulate antitumor immunity, while activation of type 1 T cells promotes antitumor immunity. However, the immunological features of liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) treated by intra-arterial chemotherapy are still unclear. The aim of this study was to assess the influence of intra-arterial combination chemotherapy on the Th1/Th2 balance in LC patients with aHCC. Twenty-one adult Japanese LC patients with aHCC were treated by intra-arterial combination chemotherapy. The control group was composed of 20 adult Japanese patients with chronic hepatitis C diagnosed from examination of liver biopsy specimens. All control patients were over 55 years old and were stage 1 according to the fibrosis score of Desment. Thirteen of the 21 aHCC patients (group R) showed an objective response, but the other 8 patients (group N) showed no response. There were no significant differences of Th1 cells between group R and group N either before or after chemotherapy. Although there was no significant difference from group R, group N had a significantly higher percentage of Th2 cells than the control group both before and after chemotherapy (p < 0.05 by Tukey's test). These results indicate that the Th1/Th2 balance might be a useful indicator of the effect of intra-arterial combination chemotherapy in LC patients with aHCC. Inhibition of an increase of Th2 cells might be important for the efficacy of intra-arterial chemotherapy in such patients.
    Cancer Chemotherapy and Pharmacology 02/2008; 62(6):959-63. · 2.80 Impact Factor
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    ABSTRACT: To investigate the role of matrix metalloproteinases (MMPs) during gastrointestinal tract development, the expression of gelatinases (MMP-2 and MMP-9) was investigated during fetal rat colon morphogenesis. Fetal rat colons were separated into epithelial and mesenchymal fractions without cross contamination using a chelating agent and a dissecting microscope. Gelatinase activity measured using fluorescently labeled gelatin was higher in the mesenchymal than in the epithelial fraction; the developmental profile revealed that, in both fractions, gelatinase activity was enhanced during colon morphogenesis. During colonic gland formation, there was prominent MMP-2 activity, elevated MMP-2 mRNA expression, and an increase in the level of the active form of MMP-2 in the mesenchymal fraction. The mRNA expression of the tissue inhibitor of metalloproteinase 2 corresponded with an elevation in the level of the active form of MMP-2; the mRNA expression of the cell surface activator of MMP-2, membrane type matrix metalloproteinase 1, did not increase significantly. MMP-9 activity was low; only the pro-form was observed in the epithelial fraction at the end of fetal life. These results suggest that, during colon morphogenesis, MMP activity is under strict spatio-temporal control, and that the activity of MMP-2, which is regulated at both the transcriptional and proteolytic activation levels, is very much involved in rat colon morphogenesis.
    Embryologia 02/2008; 50(1):41-8. · 2.18 Impact Factor
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    ABSTRACT: Gastric acid plays an important part in the prevention of bacterial colonization of the gastrointestinal tract. If these bacteria have an ability of hydrogen (H2) fermentation, intraluminal H2 gas might be detected. We attempted to measure the intraluminal H2 concentrations to determine the bacterial overgrowth in the gastrointestinal tract. Studies were performed in 647 consecutive patients undergoing upper endoscopy. At the time of endoscopic examination, we intubated the stomach and the descending part of the duodenum without inflation by air, and 20 mL of intraluminal gas samples of both sites was collected through the biopsy channel. Intraluminal H2 concentrations were measured by gas chromatography. Intragastric and intraduodenal H2 gas was detected in 566 (87.5%) and 524 (81.0%) patients, respectively. The mean values of intragastric and intraduodenal H2 gas were 8.5 +/- 15.9 and 13.2 +/- 58.0 ppm, respectively. The intraduodenal H2 level was increased with the progression of atrophic gastritis, whereas the intragastric H2 level was the highest in patients without atrophic gastritis. The intraduodenal hydrogen levels were increased with the progression of atrophic gastritis. It is likely that the influence of hypochlorhydria on bacterial overgrowth in the proximal small intestine is more pronounced, compared to that in the stomach.
    Gastroenterology Research and Practice 02/2008; 2008:584929. · 1.62 Impact Factor
  • Clinical Nutrition Supplements 01/2008; 3:88-88.

Publication Stats

4k Citations
730.29 Total Impact Points


  • 1999–2009
    • Toho University
      • • Department of Gastroenterology and Hepatology
      • • Department of General Medicine and Emergency Care
      • • Department of Internal Medicine
      • • Faculty of Medicine
      Edo, Tōkyō, Japan
    • Kyorin University
      Edo, Tōkyō, Japan
  • 1993–2008
    • Aichi Cancer Center
      Ōsaka, Ōsaka, Japan
  • 1973–2008
    • The University of Tokyo
      • Division of Internal Medicine
      Edo, Tōkyō, Japan
  • 2003
    • National Cancer Center, Japan
      • Endoscopy Division
      Edo, Tōkyō, Japan
  • 1989–2001
    • Kyoto University
      • • Division of Chemistry
      • • Division of Applied Life Sciences
      • • Primate Research Institute
      Kyoto, Kyoto-fu, Japan
    • National University of Malaysia
      • Department of Surgery
      Kuala Lumpur, Kuala Lumpur, Malaysia
  • 1998
    • Tokyo Metropolitan Institute of Gerontology
      Edo, Tōkyō, Japan
  • 1995
    • Hokkaido University Hospital
      • Division of Internal Medicine II
      Sapporo-shi, Hokkaido, Japan
    • Chiba University
      • Faculty of Horticulture
      Chiba-shi, Chiba-ken, Japan
  • 1993–1995
    • Tokyo Institute of Technology
      Edo, Tōkyō, Japan
  • 1994
    • Hokkaido University
      • Faculty of Science
      Sapporo, Hokkaidō, Japan
  • 1986–1993
    • Nagoya City University
      • Medical School
      Nagoya, Aichi, Japan
  • 1990–1991
    • Osaka University
      • Division of Applied Chemistry
      Suika, Ōsaka, Japan
  • 1987
    • Gifu Pharmaceutical University
      Edo, Tōkyō, Japan