T Mori

Gifu University, Gihu, Gifu, Japan

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Publications (501)1031.08 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNA (miR)-203 is downregulated and acts as an anti-oncomir in melanoma cells. Here, using human and canine melanoma cells, we elucidated the effects of miR-203 on cyclic adenosine monophosphate response element binding protein (CREB)/microphthalmia-associated transcription factor (MITF)/RAB27a pathway, which is known to be important for the development and progression of human melanoma. In this study, we showed that miR-203 directly targeted CREB1 and regulated its downstream targets, MITF and RAB27a. miR-203 significantly suppressed the growth of human and canine melanoma cells and inhibited melanosome transport through the suppression of the signalling pathway. In conclusion, miR-203 was shown to be a common tumour-suppressive miRNA in human and canine melanoma and thus to play a crucial role in the biological mechanisms of melanoma development.
    Veterinary and Comparative Oncology 09/2014; · 1.56 Impact Factor
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    ABSTRACT: Malignant melanoma (MM) is one of the most aggressive cancers in dogs and in humans. However, the molecular mechanisms of its development and progression remain unclear. Presently, we examined the expression profile of microRNAs (miRs) in canine oral MM tissues and paired normal oral mucosa tissues by using the microRNA-microarray assay and quantitative RT-PCR. Importantly, a decreased expression of miR-203 was significantly associated with a shorter survival time. Also, miR-203 and -205 were markedly down-regulated in canine and human MM cell lines tested. Furthermore, the ectopic expression of miR-205 had a significant inhibitory effect on the cell growth of canine and human melanoma cells tested by targeting erbb3. Our data suggest that miR-203 is a new prognostic factor in canine oral MMs and that miR-205 functions as a tumour suppressor by targeting erbb3 in both canine and human MM cells.
    Veterinary and Comparative Oncology 06/2013; 11(2):113-23. · 1.56 Impact Factor
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    ABSTRACT: We examined whether mutation of the platelet-derived growth factor receptor protein tyrosine kinase (PDGFR)-α and PDGFR-β genes contributes to their overexpression in canine vascular tumours. Genomic sequences of trans- or juxtamembrane regions of PDGFR-α and PDGFR-β were analysed with immunohistochemical staining and polymerase chain reaction-direct sequencing using DNA from paraffin-embedded neoplastic tissues of 27 hemangiosarcomas (HSAs) and 20 hemangiomas (HAs). Immunohistochemically, 75% of the HA cases were positive for PDGFR-α and almost most of the HA cases were negative for PDGFR-β. Of the HSA cases, 55.6% were negative for PDGFR-α and 63% were strongly positive for PDGFR-β. Among the HA cases, 1 missense mutation was detected in PDGFR-α exon 18 and 1 in PDGFR-β exon 17. Two HSA cases had missense mutations in exon 14 and 1 in exon 17 of PDGFR-β. Thus, genomic mutation of trans- or juxtamembrane regions of PDGFRs was not the main mechanism driving the activation of receptors in HSA and HA.
    Veterinary and Comparative Oncology 04/2013; · 1.56 Impact Factor
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    ABSTRACT: An 11-year-old male Bearded Collie was brought to the Gifu University Animal Medical Centre with a skin mass on the lateral right thigh. Physical examination revealed a 30 × 65-mm oval mass with an alopecic and ulcerated surface. Histopathology of the surgically excised sample confirmed malignant trichoepithelioma. Five months after the surgery, the dog experienced lumbar pain resulting from metastasis to the lumbar vertebrae. Radiation therapy (RT) was performed and it alleviated the lumbar pain. Nine months after the surgery, multiple skin metastases were identified. RT was performed at each occurrence, which reduced the size of each tumour and resulted in a partial response; however, systemic metastasis occurred and the dog died 17 months after the initial surgery. Canine malignant trichoepithelioma is a rare tumour, so an effective treatment has not been determined. Data from our case study indicate that RT has potential for pain control of primary and metastatic malignant trichoepithelioma.
    Australian Veterinary Journal 06/2012; 90(6):210-3. · 0.92 Impact Factor
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    ABSTRACT: Hemangiosarcoma (HSA) is a malignant neoplasia of vascular endothelial cells (ECs). Our previous report on the expression of vascular endothelial growth factor, basic fibroblast growth factor, and their receptors in canine HSA suggested an autocrine/ paracrine mechanism of tumor growth. However, the influence of other angiogenic growth factors in canine HSA was not elucidated; therefore, the expression of platelet-derived growth factor (PDGF) and its receptors was investigated by immunohistochemical analysis. Forty-six canine HSAs and 21 canine cutaneous hemangiomas (HAs) were analyzed. For immunohistochemistry, anti-PDGF-BB, anti-PDGFR-α, and anti-PDGFR-β antibodies were utilized as primary antibodies. Immunoreactivities were scored as strongly positive (>25% positive neoplastic cells), weakly positive (1-25% positive neoplastic cells), and negative if not staining at all. In cutaneous HA, 33.3% and 57.1% of cases were strongly and weakly positive, respectively, and 43.5% and 13.0% of HSAs were strongly and weakly positive for PDGF-BB, respectively. Moreover, 38.1% and 28.6% of cutaneous HAs cases were strongly and weakly positive, respectively, and 23.9% and 4.3% of HSAs cases were strongly and weakly positive, respectively, for PDGFR-α. Thirty-five HSAs cases (76.1%) were strongly positive, and the remaining 11 (23.9%) were weakly positive for PDGFR-β. In contrast, 18 (72.0%) cutaneous HAs were negative, and only 3 cases (12.0%) were weakly positive, for PDGFR-β. The proportion of strongly positive cases of HSAs was significantly higher than that of cutaneous HA for PDGFR-β (P<0.01), while PDGFR-α was highly expressed in cutaneous HA and may be related to pathogenesis of cutaneous HA. Therefore, PDGFR-β may be associated with the malignant nature of canine HSA.
    Histology and histopathology 05/2012; 27(5):601-7. · 2.28 Impact Factor
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    ABSTRACT: Fascin-1 expression was examined in 9 cutaneous melanocytomas and 47 oral melanomas. The cases were scored on the basis of extent and intensity of staining, and combined scores were calculated. Fascin-1 expression was observed in 5/9 (56%) melanocytomas and 46/47 (98%) melanomas. The combined score for fascin-1 was significantly greater in stage III/IV melanomas than in stage I/II melanomas (P < 0.05). In addition, strong fascin-1 staining was associated with a significantly shortened survival time (P < 0.05). The results of this study suggest that fascin-1 overexpression correlates with the malignancy of canine melanoma and has the potential to be a new immunohistochemical marker to predict the clinical course of canine melanoma. In addition, targeted therapy for fascin-1 may represent a new strategy for the treatment of canine melanoma.
    Veterinary and Comparative Oncology 11/2011; · 1.56 Impact Factor
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    ABSTRACT: KIT, a transmembrane receptor tyrosine kinase, is one of the specific targets for anti-cancer therapy. In humans, its expression and mutations have been identified in malignant melanomas and therapies using molecular-targeted agents have been promising in these tumours. As human malignant melanoma, canine malignant melanoma is a fatal disease with metastases and the poor response has been observed with all standard protocols. In our study, KIT expression and exon 11 mutations in dogs with histologically confirmed malignant oral melanomas were evaluated. Although 20 of 39 cases were positive for KIT protein, there was no significant difference between KIT expression and overall survival. Moreover, polymerase chain reaction amplification and sequencing of KIT exon 11 in 17 samples did not detect any mutations and proved disappointing. For several reasons, however, KIT expression and mutations of various exons including exon 11 should be investigated in more cases.
    Veterinary and Comparative Oncology 09/2011; 9(3):219-24. · 1.56 Impact Factor
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2010; 27(52).
  • The Veterinary record 09/2009; 165(12):350-1. · 1.80 Impact Factor
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    ABSTRACT: Angiogenic homeobox genes regulate the behaviour of endothelial cells (ECs) during angiogenesis, so the aim of this study was to determine whether expression of these genes may be a determinant of malignancy in canine haemangiosarcoma (HSA). Homeobox proteins were evaluated immunohistochemically in tissue samples from canine HSAs (n=78), haemangiomas (HAs; n=30) and samples of granulation tissue (n=8). Active ECs in granulation tissue were positively labelled by antisera specific for HoxA9, HoxB3, HoxD3, HoxB7, Pbx1 and Meis1. Quiescent ECs in granulation tissue did not express HoxD3 and Pbx1. There were significantly more neoplastic cells positively labelled for HoxA9, HoxB3, HoxD3 and Pbx1 in HSA compared with HA. Almost all tumours were positive for HoxB7 and Meis1. HoxB3, HoxD3, Pbx1 and Meis1 proteins were detected in 80-90% of the HSAs, but in <20% of the HAs. Overall, homeobox protein expression in HSA appears to have a phenotype similar to that of active ECs in angiogenesis. The expression of homeobox genes associated with angiogenesis might be associated with the malignant growth of HSA.
    Journal of comparative pathology 06/2009; 141(2-3):199-203. · 1.73 Impact Factor
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    ABSTRACT: We performed immunohistochemical investigation of the basement membrane (BM) components, namely, type IV collagen and laminin, in 83 canine hemangiosarcomas (HSAs), 22 hemangiomas, and some granulation tissues (GTs). Additionally, we analyzed the expression and activities of matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1-MMP (MT1-MMP) using the same samples by immunohistochemistry and gelatin zymography to investigate whether MMPs were associated with the BM degradation. In immunohistochemistry for the BM components, many HSAs showed discontinuous linear/negative immunoreactivity in the BM (type IV collagen: 49.4%/14.5%, laminin: 60.3%/10.8%, respectively). In contrast, almost all hemangiomas showed continuous staining in the BM (type IV collagen: 90.9%, laminin: 95.5%, respectively). Interestingly, positive cytoplasmic immunoreactivity for type IV collagen and laminin was observed in 97.6% and 91.6% HSA, respectively. Although MMP-9 immunoreactivity wasn't detected in neoplastic and active angiogenic endothelial cells (ECs), MMP-2 was detected in all ECs of GTs and in neoplastic cells of both vascular tumors. A strong immunoreactivity for MT1-MMP was observed in active angiogenic ECs in GTs and in neoplastic ECs in HSAs. However, almost all hemangiomas showed weak/negative immunoreactivity. In gelatin zymography, significantly strong activity of active MMP-2 was observed in HSAs, similar to that in active angiogenesis in GTs; however, weak/no activity of active MMP-2 was detected in hemangiomas. In canine HSA, neoplastic cells had active MMP-2, possibly activated by MT1-MMP, and discontinuous status of BM might be associated with activity of active MMP-2.
    Histology and histopathology 05/2009; 24(4):437-46. · 2.28 Impact Factor
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    ABSTRACT: To investigate whether anti-apoptotic factors play a role in the malignant growth of canine haemangiosarcomas (HSAs), 83 HSAs and 22 haemangiomas were examined immunohistochemically for bcl-2 and survivin expression. Additionally, bcl-2 and survivin mRNA expression was quantified by semiquantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). Immunolabelling for bcl-2 was observed in 50 of the 83 HSA samples (60.2%) but in none of the haemangiomas. The average survivin positive index was 24.7% in the HSAs and 0.6% in the haemangiomas. In contrast to the high average value for survivin mRNA expression, which was approximately six times that for the haemangiomas, no significant difference was observed between HSAs and haemangiomas for the average bcl-2 mRNA expression level. The discrepancy between bcl-2 mRNA and bcl-2 protein expression requires further investigation, but the results suggest that malignant proliferation in canine HSAs is associated with bcl-2 and survivin expression.
    Journal of Comparative Pathology 08/2008; 139(1):1-7. · 1.38 Impact Factor
  • Medical Mycology - MED MYCOL. 01/2008; 36(2):107-112.
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    ABSTRACT: During a search for causative genes in patients with concurrent multiple primary colon tumours, we found a novel case with a germline mutation of the p53 gene, from GCC (Ala) to GTC (Val) at codon 189. Of the six primary colon tumours that this patient had, one large advanced carcinoma exhibited a somatic p53 mutation and a somatic APC mutation, in addition to the germline p53 mutation. Two early carcinomas and three adenomas had somatic APC mutations but no somatic p53 mutation or loss of the p53 allele. K-ras-2 mutations were detected in an advanced carcinoma and an early carcinoma. The present results suggest that a patient with a certain type of germline p53 mutation is predisposed to concurrent multiple colon tumours. It is also suggested that in such a patient, a somatic APC mutation is involved in tumour formation and that an additional somatic p53 mutation contributes to tumour progression.
    Gut 03/2003; 52(2):304-6. · 10.73 Impact Factor
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    ABSTRACT: We analyzed the effectiveness of anti-cancer chemotherapy administered at home. Continuous hepatic arterial infusion (HAI) of 5-FU (250 mg/day) for unresectable liver metastases of colorectal cancer (129 cases) and systemic administration of 5-FU and CDDP (FP therapy) as a palliative treatment or for recurrent cases of colorectal cancer (145 cases) were evaluated. The response rate for HAI was 59.7%, and 50% survival according to the outcome of HAI was CR: 765 days PR: 607 days NC: 233 days and PD: 146 days. The residual life span of patients who showed CR or PR was significantly prolonged. The occurrence of complications from HAI was 15.1%. On the other hand, the response rate was 19.3%, and 50% survival was 292 days. The one-year survival rate was 38.7%. The mean duration of this chemotherapy and the mean stay at home were 188.2 days and 237.8 days, respectively. The mean rate of home stays was 68.6%. The group of performance status (PS) 0 or improving PS accounted for 74.5% of all cases. Those with a PS grade 3 or 4 accounted for only 1-4% of the patients. Finally, both chemotherapies could be continued at the outpatient clinic or at home.
    Gan to kagaku ryoho. Cancer & chemotherapy 01/2002; 28 Suppl 1:5-8.
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    ABSTRACT: Clinically, unresectable pelvic tumor is difficult to treat because the patients have poor prognosis and often suffer from severe pain and edema of the lower limbs due to the tumor invasion of the pelvic bone and the sciatic nerve. To improve QOL of such patients, we performed thermoradiotherapy (RTHT) or internal iliac arterial infusion of 5-FU (IIAI) for 7 patients who developed unresectable pelvic tumors which relapsed after surgery for 6 colorectal cancers and one leiomyosarcoma of the uterus. The mean tumor diameter was 10.2 cm and an evaluation by computed tomography revealed 2 of 6 tumors had a partial response (PR) and 3 no change (NC). Each of the 4 patients who had been ill in bed recovered to the point of being able to walk with a cane or wheel themselves in a wheelchair after the therapy.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2001; 28(11):1612-5.
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    ABSTRACT: A 53-year-old female presented with abdominal pain, and computed tomography scan revealed a small, calcified lesion in the wall of the transverse colon. The symptoms later disappeared spontaneously, and she remained in good health. However, four years later, she developed lancinating abdominal pain and was admitted to our hospital. A large tumor with calcification was found in the left upper abdominal cavity. Curative resection of the tumor was performed, and the histology was compatible with extraskeletal osteosarcoma. We speculated that the tumor originated from the colonic wall, because a small calcification was observed in the wall of the transverse colon four years before surgery. To the best of our knowledge, this is the first report of primary colonic osteosarcoma.
    Diseases of the Colon & Rectum 10/2001; 44(9):1367-70. · 3.34 Impact Factor
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    ABSTRACT: One of the characteristics of tumors from patients with germline mutations of DNA mismatch repair genes is instability at microsatellite regions (MSI). We analysed alterations at repeated sequences of coding regions, as well as those of 5' upstream regions, in 29 MSI-High colorectal tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC) and Turcot syndrome. We found that repeated sequences in 5' upstream regions were altered in these tumors, at considerable frequencies. The (A)10 repeat in the promoter region (position -178 to approximately -169) of the GAPDH gene was altered in 17% of the tumors. The (A)10(TA)9 in the 5' upstream region (position -318 to approximately -291) of the mitochondrial isoleucyl tRNA synthetase gene (IleRS-A), coded in nuclear DNA, was altered in 59% of the tumors, whereas (A)9 in the 5' upstream region (position -859 to approximately -851) of cytoplasmic isoleucyl tRNA synthetase gene (IleRS-B) was not altered. Alteration at repeated sequences in the coding regions were 72% at TGFbetaRII(A)10, 24% at IGFIIR(G)8, 45% at BAX(G)8, 55% at E2F4(CAG)13, 66% at caspase-5 (A)10, 31% at MBD4(A)10, 55% at hMSH3(A)8 and 34% at hMSH6(C)8. The number of altered genes increased with the advancement of carcinoma according to Dukes categories: mean numbers of altered genes within these 10 genes were 2.6 for Dukes A, 4.7 for Dukes B and 7.8 for Dukes C. The mean number for adenomas was 2.0. These results suggest that the MSI phenotype also causes alteration of 5' upstream regions which may affect apoptosis and some mitochondrial functions in HNPCC and Turcot tumors, and that accumulation of altered genes with repeated sequences is associated with the progression of HNPCC and Turcot colorectal tumors.
    Oncogene 09/2001; 20(37):5215-8. · 8.56 Impact Factor
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    ABSTRACT: It may be widely interpreted that minimally invasive treatment of colorectal cancer includes endoscopic mucosal resection, transanal endoscopic microsurgery (TEM), laparoscopic surgery and open reduction-surgery as well as adjuvant treatments such as chemotherapy, radiotherapy and thermotherapy. With the development of medical technology and instruments, we have now a wide and new range of choices for each cancer stage of patients. However, it is not yet clear that minimally invasive treatment necessarily leads to better results in survival and recurrent rates of the patients, as compared with conventional surgery. We should therefore take into full consideration the lingering problems in selecting the new therapies. In this paper, we show the strong and weak points of laparoscopic surgery, TEM, right hemi-colectomy preserving Bauhin's valve and adjuvant radiotherapy for lower rectal cancer, and discuss ongoing problems.
    Gan to kagaku ryoho. Cancer & chemotherapy 09/2001; 28(8):1077-82.
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    ABSTRACT: From October 1999 to September 2000, we collected the specimen from 430 patients with lower respiratory tract infections in 17 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 515 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 506 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 101, Haemophilus influenzae 104, Pseudomonas aeruginosa (non-mucoid) 58, P. aeruginosa (mucoid) 11, Moraxella subgenus Branhamella catarrhalis 41, Klebsiella pneumoniae 18, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or above of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 57.7%. Vancomycin and arbekacin showed the most potent activities against MRSA without detection of ABK-resistant strain (MIC: 64 micrograms/ml) and decrease of VCM-sensitive strains those were found in 1998. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) decreased to 34.7% from 46.0% in 1998. The frequency of PRSP was 3.0%, being the least number after 1991. Carbapenems showed strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 101 strains with MIC of 0.063 microgram/ml. Generally, all drugs showed strong activities against H. influenzae with MIC80s of 4 micrograms/ml or below. MICs of ofloxacin ranged between 0.063 microgram/ml and 4 micrograms/ml in 1998, however, those were 0.125 microgram/ml or below in all H. influenzae in 1999 showing the strongest activity. Tobramycin and ciprofloxacin showed strong activities against P. aeruginosa (both mucoid and non-mucoid) with MIC80s of 1 microgram/ml. Number of isolated P. aeruginosa (mucoid) was little as 11, however, the susceptibilities to all drugs were better than P. aeruginosa (non-mucoid). K. pneumoniae showed good susceptibilities to all drugs except for ampicillin with decreasing of low-sensitive strains compared to those detected in 1998. Also, all drugs generally showed strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or below. The drug which showed the strongest activity was imipenem inhibiting all 41 strains with MIC of 0.063 microgram/ml. On the patients' characteristics, the number of patients aged 80 years or older who had been increased was decreased in 1999 in the distribution by age. The percentage of the elderly patients aged 70 years or older was 47.0%, which occupied almost a half number of the total patients as in the last year. As for the incidence by disease, bacterial pneumonia and chronic bronchitis were the highest. They were noted in 37.9% and 30.5% of the patients, respectively. In 1999, bronchial asthma was frequently observed as compared in recent years. It was noted in about 10% of the patients which is the same % as in bronchiectasis. We examined the number of strains from these patients with infections before and after administration of antibiotics. In patients with bacterial pneumonia, the number of isolated strains was almost the same between those before and after administration. However, in patients with chronic bronchitis, the number of strains remarkably decreased to less than the half of the total after administration of antibiotics in the last year, but it decreased to 2/3 of the total in 1999. On the administration of antibiotics and isolated bacteria by the day of administration, the bacteria which were isolated more before administration were H. influenzae in 28.4%, S. pneumoniae in 25.7%, M. (B.) catarrhalis in 12.0% and S. aureus in 10.6%. The frequency of S. aureus after administration over 15 days was almost the same as that before administration, but the frequency of P. aeruginosa (both mucoid and non-mucoid) was 36.8% which was higher than that before administration. The frequency of isolated S. pneumoniae was decreased after administration and none of them was isolated after completion of administration. However, that of H. influenzae was decreased to 7.1% after administration within 3 days, and many H. influenzae were isolated after completion of administration as 21.4%.
    The Japanese journal of antibiotics 08/2001; 54(7):331-64.

Publication Stats

6k Citations
1,031.08 Total Impact Points

Institutions

  • 2008–2011
    • Gifu University
      • Department of Veterinary Medicine
      Gihu, Gifu, Japan
  • 1991–2003
    • Tokyo Metropolitan Komagome Hospital
      Edo, Tōkyō, Japan
    • Osaka National Hospital
      Ōsaka, Ōsaka, Japan
  • 1992–2001
    • Juntendo University
      • • Department of Internal Medicine
      • • Department of Medicine
      Edo, Tōkyō, Japan
  • 1999
    • Otsuka Pharmaceutical Group
      Edo, Tōkyō, Japan
  • 1993–1997
    • The University of Tokyo
      • • Faculty and Graduate School of Agriculture and Life Sceince
      • • Department of Precision Engineering
      Tokyo, Tokyo-to, Japan
  • 1986–1997
    • Osaka University
      • • Department of Surgery
      • • Department of Medical Genetics
      • • Division of Cellular and Molecular Biology
      • • Department of Oncogene Research
      • • School of Medicine
      Suita, Osaka-fu, Japan
  • 1995
    • Samsung Medical Center
      • Department of Surgery
      Seoul, Seoul, South Korea
  • 1992–1995
    • National Institute of Radiological Sciences
      Tiba, Chiba, Japan
  • 1994
    • Kyoto University
      Kioto, Kyōto, Japan
  • 1992–1993
    • Tokyo Metropolitan Institute of Medical Science
      Edo, Tōkyō, Japan
  • 1989–1992
    • Hoshi University
      • Faculty of Pharmaceutical Sciences
      Edo, Tōkyō, Japan
  • 1988
    • Osaka Prefecture Senshu Critical Care Medical Center
      Ōsaka, Ōsaka, Japan