T Kitamura

Asoka Hospital, Edo, Tōkyō, Japan

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Publications (435)1652.55 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of the present study was to investigate the trends over time in the initial treatment of prostate cancer in Japan.
    Japanese Journal of Clinical Oncology 08/2014; · 1.90 Impact Factor
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    ABSTRACT: Objectives To investigate the association between the TMPRSS2 Met160Val polymorphism and the risk of prostate cancer in Japanese men.Methods Genomic DNA samples from 518 Japanese sporadic prostate cancer patients, 433 controls and 154 Japanese men who were diagnosed as having latent prostate cancer based on autopsy results were genotyped for the TMPRSS2 Met160Val polymorphism using a TaqMan assay. Logistic regression analyses were carried out to estimate the odds ratios and 95% confidence intervals. The relationship between the presence of the polymorphism, and clinicopathology and survival was also examined.ResultsThe T allele frequency of the control group was 0.372, of the sporadic prostate cancer group was 0.435 and of the latent prostate cancer group was 0.370. The CT and TT genotypes were significantly associated with risk for sporadic prostate cancer; age-adjusted odds ratios (95% confidence intervals) were 1.418 (1.027–1.960) for CT, 1.907 (1.224–2.990) for TT and 1.524 (1.123–2.072) for CT/TT genotypes. There was no significant association observed between the TMPRSS2 Met160Val polymorphism and the risk for latent prostate cancer. The TMPRSS2 Met160Val polymorphism was not significantly associated with any clinicopathological features or prognosis.Conclusions The TMPRSS2 Met160Val polymorphism is a genetic risk factor for sporadic prostate cancer in a Japanese population.
    International Journal of Urology 08/2014; · 1.73 Impact Factor
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    ABSTRACT: “LEOPIN ROYAL®” (LER), a non-prescription health-promoting medication in Japan, is a preparation containing six natural medicines, namely, aged garlic extract, ginseng, oriental bezoar, velvet antler, cuscuta seed and epimedium herb. To determine the effect of LER on symptoms of aging in males, we conducted an open-labeled, randomized clinical trial using Kampo (mainly kamishoyosan) as a control. Forty-nine male patients (age, 62.7 (SD 11.8) years) with mild or more pronounced symptoms of aging were enrolled and randomly assigned to the LER (n = 24) or Kampo group (n = 25) for 6 months. The Aging Males’ Symptoms (AMS) scale and the International Index of Erectile Function with 5 questions (IIEF-5) were tested at baseline, and after 3 and 6 months of administration of the medications. In the AMS scale, the somatic and psychological sub-scores and total score decreased depending on the time course in both groups. However, the decrease in the slope of the LER group was greater than that of the Kampo group. There was a significant difference between the groups and the group and month interaction (G × M), as revealed by a linear mixed model analysis (p < 0.05). The IIEF-5 score increased in the LER group (p = 0.02 with regard to G × M). In conclusion, the present results indicate that LER is possibly superior to mainly kamishoyosan on the rate of improvement of symptoms of aging, including erectile dysfunction, in males.
    The Aging Male 05/2014; 17(2). · 1.71 Impact Factor
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    ABSTRACT: Primary androgen deprivation therapy (PADT) had been used extensively in Japan than in the USA and European countries regardless of the disease risk or patient's age. To illustrate the consequence of PADT from daily clinical practice, we evaluated the relationship among age, disease risk, and survival of patients with prostate cancer treated by PADT in largest Asian cohort. The 19,246 men subjected to PADT enrolled in the Japan Study Group of Prostate Cancer were enrolled for the present analysis. Patients were divided into four groups based on age at diagnosis: age <66, 66-70, 71-75, and >75. Risk was stratified according to the Japan Cancer of the Prostate Risk Assessment (J-CAPRA). Multivariate competing risks regression analysis was performed for OS and PFS. There was downward stage migration over age. Among men aged >75 years, 34.1 % had nodal or distant metastatic disease. In contrast, 56.0 % of patients aged <66 years presented with advanced disease. The modality of hormonal therapy varied with age across risk groups; the younger age group showed a higher proportion of maximal androgen blockade, while the proportion of monotherapy use was higher in older men. The likelihood of low-risk disease by J-CAPRA classification increased significantly with increasing age (p < 0.0001 by Pearson's chi-square test). The same as OS, the PFS rate increased with age until after the age of 75. Men aged 71-75 had better survival rates even after adjustments for treatment modality alone, or for treatment modality plus disease risk. Age cohorts do affect orientation toward favorable disease course after PADT with men aged 71-75 being benefiting more from PADT than other age groups.
    Journal of Cancer Research and Clinical Oncology 03/2014; · 2.91 Impact Factor
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    ABSTRACT: To determine the influence of maximal androgen blockade (MAB) and non-MAB hormonal therapy with an luteinizing hormone releasing hormone (LHRH) analog on overall survival of prostate cancer patients in the Japan Study Group of Prostate Cancer (J-CaP) registry according to risk, as assessed using the novel J-CAPRA risk instrument. To undertake a multivariate analysis combining J-CAPRA risk score, type of hormonal therapy and comorbidities, in order to assess their impact on overall survival. The J-CaP database includes men in Japan diagnosed with any stage of prostate cancer between 2001 and 2003 and treated with primary androgen deprivation therapy (PADT), as monotherapy or in combination. A total of 26,272 men were enrolled and of these 19,265 were treated with PADT. This analysis was undertaken using the latest data set (30 April, 2010) including a total of 15,727 patients who received PADT and had follow-up data for periods ranging from 0 to 9.2 years. MAB for prostate cancer patients with intermediate- or high-risk disease has a significant benefit in terms of overall survival compared with LHRH analog monotherapy or surgical castration alone. Better results may be achieved in older (≥75 years) patients. Patient comorbidities are an important factor in determining overall survival, notably in older patients, and should be considered when selecting therapy. Based on large-scale registry data, this report is the first to analyze the outcomes of MAB therapy in patients with prostate cancer at a wide range of disease stages. MAB therapy may provide significant survival benefits in intermediate- and high-risk patients.
    Prostate international. 01/2013; 1(2):81-8.
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    ABSTRACT: Ras guanyl nucleotide-releasing proteins (RasGRPs) are activators of Ras. Previous studies have indicated the possible involvement of RasGRP1 and RasGRP4 in leukemogenesis. Here, the predominant role of RasGRP1 in T-cell leukemogenesis is clarified. Notably, increased expression of RasGRP1, but not RasGRP4, was frequently observed in human T-cell malignancies. In a mouse bone marrow transplantation model, RasGRP1 exclusively induced T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) after a shorter latency when compared with RasGRP4. Accordingly, Ba/F3 cells transduced with RasGRP1 survived longer under growth factor withdrawal or phorbol ester stimulation than those transduced with RasGRP4, presumably due to the efficient activation of Ras. Intriguingly, NOTCH1 mutations resulting in a gain of function were found in 77% of the RasGRP1-mediated mouse T-ALL samples. In addition, gain-of-function NOTCH1 mutation was found in human T-cell malignancy with elevated expression of RasGRP1. Importantly, RasGRP1 and NOTCH1 signaling cooperated in the progression of T-ALL in the murine model. The leukemogenic advantage of RasGRP1 over RasGRP4 was attenuated by the disruption of a protein kinase C phosphorylation site (RasGRP1(Thr184)) not present on RasGRP4. In conclusion, cooperation between aberrant expression of RasGRP1, a strong activator of Ras, and secondary gain-of-function mutations of NOTCH1 have an important role in T-cell leukemogenesis.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 11/2011; 26(5):1038-45. · 10.16 Impact Factor
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    ABSTRACT: MicroRNA-125b-1 (miR-125b-1) is a target of a chromosomal translocation t(11;14)(q24;q32) recurrently found in human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This translocation results in overexpression of miR-125b controlled by immunoglobulin heavy chain gene (IGH) regulatory elements. In addition, we found that six out of twenty-one BCP-ALL patients without t(11;14)(q24;q32) showed overexpression of miR-125b. Interestingly, four out of nine patients with BCR/ABL-positive BCP-ALL and one patient with B-cell lymphoid crisis that had progressed from chronic myelogenous leukemia overexpressed miR-125b. To examine the role of the deregulated expression of miR-125b in the development of B-cell tumor in vivo, we generated transgenic mice mimicking the t(11;14)(q24;q32) (Eμ/miR-125b-TG mice). Eμ/miR-125b-TG mice overexpressed miR-125b driven by IGH enhancer and promoter and developed IgM-negative or IgM-positive lethal B-cell malignancies with clonal proliferation. B cells obtained from the Eμ/miR-125b-TG mice were resistant to apoptosis induced by serum starvation. We identified Trp53inp1, a pro-apoptotic gene induced by cell stress, as a novel target gene of miR-125b in hematopoietic cells in vitro and in vivo. Our results provide direct evidence that miR-125b has important roles in the tumorigenesis of precursor B cells.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 07/2011; 25(12):1849-56. · 10.16 Impact Factor
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    ABSTRACT: Recently, genome-wide association studies have independently identified multiple prostate cancer risk variants on 8q24 and 17q in European and American populations. In this study, we examined the association between three key single-nucleotide polymorphisms (SNPs) in these two regions and the risk of prostate cancer in a Japanese population. The associations between the rs6983561, rs4430796, and rs1859962 SNPs and prostate cancer susceptibility and tumor aggressiveness were examined in a total of 950 Japanese subjects (518 with sporadic prostate cancer (SPCa), 109 with latent prostate cancer (LPCa), and 323 controls). After adjustments for age, the C allele of rs6983561 and the A allele of rs4430796 were significantly more frequent among the SPCa patients than among the controls. Men who carry these risk alleles have an estimated odds ratio (OR) of 1.55 and 1.35, respectively. Furthermore, the SNPs rs6983561 and rs4430796 were associated with a susceptibility to aggressive prostate cancer, whereas rs1859962 was associated with non-aggressive prostate cancer. However, no significant difference was observed between these three polymorphisms and the risk of LPCa. We also examined the cumulative association of these three SNPs and prostate cancer susceptibility. Compared with men who do not have any risk alleles, the ORs increased according to the number of risk alleles that were present (P-value for trend: 8.1 × 10(-4) ). Our results further confirmed that variants at 8q24 and 17q are associated with the risk of prostate cancer and play an important role in tumor aggressiveness.
    The Prostate 07/2011; 71(10):1023-32. · 3.84 Impact Factor
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    ABSTRACT: We conducted present study to address whether the rs6983561 polymorphism, an established genetic marker for prostate cancer susceptibility, was a prognostic indicator. We genotyped 518 Japanese patients with prostate cancer and analysed their survival retrospectively. As a result, patients with the CA/CC genotype of rs6983561 survived significantly longer than those with the AA genotype (P = .033). Genome-wide association studies have revealed several genetic variants at 8q24 that are associated with prostate cancer susceptibility. Rs6983561 (A/C) is a single-nucleotide polymorphism located at 8q24 that has been established as a genetic risk marker for prostate cancer susceptibility. The present study investigated the association between the rs6983561 polymorphism and prostate cancer mortality in a Japanese population. The study examined 518 native Japanese male patients with sporadic prostate cancer. Germline DNA samples were obtained from all participants and genotyping of rs6983561 was performed using a TaqMan assay. Observation periods were from the date of diagnosis of prostate cancer to May 21, 2010. The Cox proportional hazards model was used to estimate the cause-specific survival (CSS) and the overall survival (OS). Patients with the CA/CC genotype of rs6983561 survived significantly longer than those with the AA genotype. In a multivariate model, the hazard ratios (HRs) and 95% confidence intervals (CIs) of the CSS and the OS for the rs6983561 polymorphism were 2.438 (1.262 - 5.046, P = .007) and 1.957 (1.142 - 3.485, P = .014), respectively. When the analysis was restricted to subjects with metastatic disease, the HRs of the CSS and the OS were 3.353 (95% CI, 1.689 - 7.446; P = 3.76 x 10(-4)) and 3.361 (95% CI, 1.741 - 7.136; P = 1.70 x 10(-4)), respectively. In the Japanese population examined in this study, the rs6983561 polymorphism at 8q24 was significantly associated with prostate cancer mortality, especially among patients with metastatic disease.
    Clinical Genitourinary Cancer 06/2011; 9(1):46-52. · 1.43 Impact Factor
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    ABSTRACT: To clarify the survival benefit of immunotherapy for renal cell carcinoma patients with lung metastasis using low-dose interleukin-2 plus interferon-α, we examined survival outcomes and factors associated with prognosis. This was a multicenter prospective study. Nephrectomized renal cell carcinoma patients with lung metastasis were treated with interleukin-2 (0.7 × 10(6) unit, 5 days a week) and interferon-α (6 × 10(6) IU, 3 days a week) for the first 8 weeks, and then with both interleukin-2 and interferon-α, 2 or 3 days a week for 16 additional weeks. Median follow-up period for 42 patients was 28.3 months (range: 4.2-43.8). Two-year overall survival rate was 82% and the probability of 3 year survival rate was 71%. Median progression-free survival was 10.4 months. While no difference was found in survival among patients assessed as complete response, partial response and no change, survival of patients assessed as NC or better was significantly better than those assessed as progressive disease (P < 0.0001). Furthermore, multivariate analyses identified pre-treatment serum sodium (P = 0.004) as an independent prognostic factor. The sodium level was also statistically associated with tumor response (p = 0.035). Patients with normal sodium level survived significantly longer (P = 0.0005) than those with low sodium level showing median survival of 12.2 months. Combination immunotherapy with low-dose interleukin-2 plus interferon-α showed survival benefit for patients with lung metastasis whose tumor responded as no change or better. This combination immunotherapy could be beneficial for patients selected by metastatic organ and their pre-treatment serum sodium level.
    Japanese Journal of Clinical Oncology 06/2011; 41(8):1023-30. · 1.90 Impact Factor
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    ABSTRACT: Prostate cancer development is associated with hyperactive androgen signaling. However, the molecular link between androgen receptor (AR) function and humoral factors remains elusive. A prostate cancer mouse model was generated by selectively mutating the AR threonine 877 into alanine in prostatic epithelial cells through Cre-ERT2-mediated targeted somatic mutagenesis. Such AR point mutant mice (ARpe-T877A/Y) developed hypertrophic prostates with responses to both an androgen antagonist and estrogen, although no prostatic tumor was seen. In prostate cancer model transgenic mice, the onset of prostatic tumorigenesis as well as tumor growth was significantly potentiated by introduction of the AR T877A mutation into the prostate. Genetic screening of mice identified Wnt-5a as an activator. Enhanced Wnt-5a expression was detected in the malignant prostate tumors of patients, whereas in benign prostatic hyperplasia such aberrant up-regulation was not obvious. These findings suggest that a noncanonical Wnt signal stimulates development of prostatic tumors with AR hyperfunction.
    Proceedings of the National Academy of Sciences 03/2011; 108(12):4938-43. · 9.81 Impact Factor
  • Journal of Urology - J UROL. 01/2011; 185(4).
  • European Urology Supplements - EUR UROL SUPPL. 01/2011; 10(2):146-146.
  • M. Nakamura, H. Kume, Y. Homma, T. Kitamura
    European Urology Supplements - EUR UROL SUPPL. 01/2011; 10(2):165-165.
  • Urology 01/2011; 78(3). · 2.42 Impact Factor
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    ABSTRACT: Ewing's sarcoma (EWS) is a malignant bone tumor that frequently occurs in teenagers. Genetic mutations which cause EWS have been investigated, and the most frequent one proved to be a fusion gene between EWS gene of chromosome 22 and the FLI1 gene of chromosome 11. However, a limited numbers of useful biological markers for diagnosis of EWS are available. In this study, we identified ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs) as a possible tumor marker for EWS using the retrovirus-mediated signal sequence trap method. ADAMTS4 is a secreted protein of 837 amino acids with a predicted molecular mass of 98-100 kDa. It is a member of metalloprotease family, is expressed mainly in cartilage and brain, and regulates the degradation of aggrecans. ADAMTS4 has been suggested to be involved in arthritic diseases and gliomas. Herein, we show that ADAMTS4 mRNA was expressed in all primary EWS samples and all EWS-derived cell lines examined, while its expression was detected only in small subpopulations of other solid tumors. Furthermore, ADAMTS4 expression was found to be regulated by EWS-FLI1 fusion gene-dependent manner. We also demonstrated that ADAMTS4 protein was highly expressed in tumor samples of the patients with EWS by using immunohistochemistry. These results suggest that ADAMTS4 is a novel tumor marker for EWS.
    International Journal of Oncology 09/2010; 37(3):569-81. · 2.66 Impact Factor
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    ABSTRACT: Activation-induced cytidine deaminase (AID) diversifies immunoglobulin through somatic hypermutation (SHM) and class-switch recombination (CSR). AID-transgenic mice develop T-lymphoma, indicating that constitutive expression of AID leads to tumorigenesis. Here, we transplanted mouse bone marrow cells transduced with AID. Twenty-four of the 32 recipient mice developed T-lymphoma 2-4 months after the transplantation. Surprisingly, unlike AID-transgenic mice, seven recipients developed B-leukemia/lymphoma with longer latencies. None of the mice suffered from myeloid leukemia. When we used nude mice as recipients, they developed only B-leukemia/lymphoma, presumably due to lack of thymus. Analysis of AID mutants suggested that an intact form with SHM activity is required for maximum ability of AID to induce lymphoma. Except for a K-ras active mutant in one case, specific mutations could not be identified in T-lymphoma; however, Notch1 was constitutively activated in most cases. Importantly, truncations of Ebf1 or Pax5 were observed in B-leukemia/lymphoma. In conclusion, this is the first report on the potential of AID overexpression to promote B-cell lymphomagenesis in a mouse model. Aberrant expression of AID in bone marrow cells induced leukemia/lymphoma in a cell-lineage-dependent manner, mainly through its function as a mutator.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 04/2010; 24(5):1018-24. · 10.16 Impact Factor
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    International Journal of Urology 04/2010; 17(4):302-13. · 1.73 Impact Factor
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    ABSTRACT: In our previous study, a combination therapy of interleukin-2 and interferon-alpha was found to be more effective than monotherapy, especially for lung metastasis. In order to determine the genetic markers of those who positively responded, a multi-institutional open study was conducted on the patients with lung metastasis. In this paper, the clinical response to our combination therapy is reported. Untreated patients with lung metastasis were enrolled in this study. Patients received interleukin-2 (0.7 x 10(6) U/day) and interferon-alpha (6 x 10(6) IU/day): interleukin-2, 5 days a week and interferon-alpha, 3 days a week for the first 8 weeks, and then both interleukin-2 and interferon-alpha, 2 or 3 days a week for 16 additional weeks. Forty-two patients were able to be evaluated for response. The overall positive response rate was 35.7% (15 of 42) including 2 patients with complete response. Progression-free patients were observed more frequently in patients with lung metastasis only (80.6%) than those with lung plus other organ metastasis (54.5%). Tumor shrinkage was observed in 81.0% (34 of 42) of patients. Progression-free survival rate at 200 days was 63.6%. Toxicities observed were primarily flu-like symptoms due to the cytokines and were typical of those observed with each single agent. Combination therapy of interleukin-2 and interferon-alpha was confirmed to be effective for renal cell carcinoma patients with lung metastasis. Identification of genetic markers is now ongoing with the tissue samples from this trial.
    Japanese Journal of Clinical Oncology 04/2010; 40(7):684-9. · 1.90 Impact Factor
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    ABSTRACT: Interleukin (IL)-2 and interferon (IFN)-α combination therapy for metastatic renal cell carcinoma (RCC) improves the prognosis for a subset of patients, while some patients suffer from severe adverse drug reactions with little benefit. To establish a method to predict responses to this combination therapy (approximately 30% response rate), the gene expression profiles of primary RCCs were analyzed using an oligoDNA microarray consisting of 38,500 genes or ESTs, after enrichment of the cancer cell population by laser micro-beam microdissection. The analysis of 10 responders and 18 non-responders identified 24 genes that exhibited significant differential expression between the two groups. In addition, the patients whose tumors did not express HLA-DQA1 or HLA-DQB1 molecules demonstrated poor clinical response. Exclusion of patients with tumors lacking either of these two genes is likely to improve the response rate to IL-2 and IFN-α combination therapy from 30 to 67%, indicating that a simple pretreatment test provides useful information with which to subselect patients with renal cancer in order to improve the efficacy of this treatment and reduce unnecessary medical costs.
    Experimental and therapeutic medicine 01/2010; 1(6):955-961. · 0.34 Impact Factor

Publication Stats

10k Citations
1,652.55 Total Impact Points

Institutions

  • 2009–2014
    • Asoka Hospital
      Edo, Tōkyō, Japan
  • 1987–2014
    • The University of Tokyo
      • • Department of Urology and Andrology
      • • Department of Surgical Sciences
      • • Faculty & Graduate School of Medicine
      Edo, Tōkyō, Japan
  • 2010
    • University of Tsukuba
      • Department of Urology
      Tsukuba, Ibaraki-ken, Japan
  • 2000–2009
    • Tokyo Medical University
      • Division of Urology
      Edo, Tōkyō, Japan
  • 2008
    • Hokkaido Memorial Hospital Of Urology
      Sapporo, Hokkaidō, Japan
  • 2007
    • Osaka City University
      • Graduate School of Medicine
      Ōsaka, Ōsaka, Japan
  • 2006–2007
    • National Institute of Police Science Japan
      Tiba, Chiba, Japan
    • The Institute of Statistical Mathematics
      Edo, Tōkyō, Japan
  • 2005
    • University of Turku
      • Department of Forensic Medicine
      Turku, Western Finland, Finland
  • 2003–2005
    • National Cancer Center
      • Center for Cancer Control and Information Services
      Edo, Tōkyō, Japan
  • 1992–2004
    • Mitsui Memorial Hospital
      Edo, Tōkyō, Japan
  • 2002
    • The Scripps Research Institute
      • Department of Molecular and Experimental Medicine
      La Jolla, CA, United States
    • Aichi Gakuin University
      • Department of Dentistry
      Nagoya-shi, Aichi-ken, Japan
  • 1980–2002
    • Kyushu University
      • • Department of Earth and Planetary Sciences
      • • Department of Physics
      Hukuoka, Fukuoka, Japan
  • 2001
    • Sanno Hospital
      Edo, Tōkyō, Japan
  • 2000–2001
    • University of North Carolina at Chapel Hill
      • Department of Pharmacology
      North Carolina, United States
  • 1988–2001
    • Juntendo University
      • Division of Gastroenterology
      Tokyo, Tokyo-to, Japan
  • 1999
    • Tokyo Metropolitan Police Hospital
      Edo, Tōkyō, Japan
  • 1998
    • Wakayama Medical University
      Wakayama, Wakayama, Japan
  • 1990–1998
    • Kitasato University
      • Division of Microbiology
      Edo, Tōkyō, Japan
  • 1990–1996
    • Palo Alto Institute for Research and Education
      Palo Alto, California, United States
  • 1995
    • Stanford University
      Palo Alto, California, United States
  • 1991
    • Nerima General Hospital
      Edo, Tōkyō, Japan