J Numaga

Tokyo Metropolitan Geriatric Medical Center, Edo, Tōkyō, Japan

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Publications (65)173.35 Total impact

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    ABSTRACT: BACKGROUND: We describe a HLA-B27-positive Japanese man with recurrent severe anterior uveitis OU and ankylosing spondylitis (AS) who was successfully treated with infliximab. CASE: A 25-year-old HLA-B27-positive Japanese man presented with recurrent anterior uveitis OU. The symptoms were consistent with typical HLA-B27-associated uveitis, whereas the subsequent course, which consisted of frequent episodes of recurrent severe anterior uveitis, was atypical. Although the patient was treated with intensive topical corticosteroids, cycloplegic treatment, sub-Tenon triamcinolone acetonide injections, systemic corticosteroids and immunosuppressive agents, recurrence of the anterior uveitis persisted. Over 8 years there were 14 documented episodes of recurrent anterior uveitis OD and 10 OSs. At age 33, the patient was diagnosed with AS after a radiographic examination. We began infusions of infliximab (2.5 mg/kg) at 0, 2 and 6 weeks, and then every 8 weeks thereafter. The recurrent uveitis disappeared, and the immunosuppressive agents and oral corticosteroids were tapered and discontinued without relapse. All drugs other than infliximab were successfully stopped in October 2010. During the follow-up period, there were no adverse events. CONCLUSION: A case of severe recurrent anterior uveitis OU in a patient with AS with infliximab was successfully treated. This is the first report describing the efficacy of infliximab in AS-associated uveitis in Japan.
    Japanese Journal of Ophthalmology 10/2012; · 1.27 Impact Factor
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    ABSTRACT: Although intraocular pressure (IOP) is the most definitive cause of glaucoma, a subtype of open angle glaucoma (OAG) termed normal tension glaucoma (NTG), which occurs in spite of normal IOP, accounts for a large part of glaucoma cases, especially in Japan. To find common genetic variants contributing to NTG in Japanese patients, we conducted a genome-wide association study (GWAS). We performed the first screening for 531,009 autosomal SNPs with a discovery cohort of 286 cases and 557 controls, and then a second screening for the top 30 suggestive loci in an independent cohort of 183 cases and 514 controls. Our findings identified a significantly associated SNP; rs523096 [combined p-value = 7.40× 10(-8), odds ratio (OR)= 2.00 with 95% confidence interval (CI) 1.55-2.58] located 10 kbp upstream of CDKN2B on chromosome 9p21. Moreover, analysis of another independent case-control set successfully replicated the results of the screening studies (combined values of all 3 stages p = 4.96 × 10(-11), OR= 2.13 with 95% CI 1.69-2.68). The SNPs near rs523096 were recently reported to be associated with OAG associated with elevated IOP in primary open-angle glaucoma (POAG), the predominant subtype of glaucoma in Caucasian populations. Our results revealed that the 9p21 locus is also associated with NTG in Japanese. In addition, we identified SNPs more strongly associated with NTG.
    PLoS ONE 01/2012; 7(7):e40107. · 3.73 Impact Factor
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    Jiro Numaga
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    ABSTRACT: This study aimed to examine the efficacy and safety of nepafenac ophthalmic suspension compared to placebo in the management of postoperative inflammation and ocular pain in Japanese patients undergoing cataract surgery. This was a multicenter, randomized, double-masked, placebo-controlled clinical study. Patients received nepafenac or placebo TID beginning 1 day before cataract surgery and continuing on the day of surgery for 14 days. One additional drop was administered on the day of surgery. The primary efficacy variables were the percentage of patients cured at postoperative day 14 visit (cure defined as aqueous cells score + aqueous flare score = 0) and the percentage of patients who were pain free at all postoperative visits. The cure rate on day 14 after surgery was 71.4% (75/105) in the nepafenac group and 28.6% (30/105) in the placebo group, showing a significant difference in cure rate between groups. The nepafenac group demonstrated higher cure rates than those in the placebo group, with a significant difference in cure rate on days 7 and 14 postoperatively. The ocular pain-free rate was 96.2% (102/106) in the nepafenac group and 67.6% (71/105) in the placebo group, showing a significant difference between groups. Concerning adverse events (AEs), 26 AEs were reported in 21 subjects (19.6%) in the nepafenac group and 31 AEs were reported in 24 subjects (22.4%) in the placebo group. Nepafenac ophthalmic suspension is a nonsteroidal anti-inflammatory drug effective in the prevention of postoperative inflammation and ocular pain associated with cataract surgery.
    Journal of ophthalmic inflammation and infection. 09/2011; 1(4):147-55.
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    ABSTRACT: Recent publications have suggested considerable improvements in the clinical outcomes of ocular Behcet's disease (BD) patients. However, the long-term time course of clinical ocular features of BD in recent cases remains largely unknown. In this study, we investigated annual time-course changes of best-corrected visual acuity (BCVA) during ocular convalescent stages, as well as annual frequency of ocular attacks during the initial 10 years of follow-up in patients with BD. We studied 75 eyes in 39 patients (31 men, eight women) with BD, who were referred to our hospital between 1980 and 1996 within 1 year after the initial ocular attack and followed them up continuously for more than 10 years. The clinical courses of BCVA at the ocular convalescent stage from the onset of ocular disease were retrospectively examined, and the numbers of ocular attacks per eye per year were determined. Mean BCVA was 0.59 at 1 year, 0.31 at 3 years, and 0.12 at 10 years from the onset of ocular disease, while the numbers of ocular attacks per eye were 4.1 +/- 3.1 at 1 year, 2.2 +/- 1.9 at 5 years, and 1.4 +/- 1.8 at 10 years. Ocular attacks were still observed in 33 eyes (45%) of 21 patients (54%) with BD even after 10 years. Final BCVA in 42 eyes (56%) became lower than 0.5. The major reasons for poor visual prognosis were macular atrophy (41%) and chorioretinal atrophy (26%). The decline of BVCA continued, and nearly half the patients still suffered from ocular attacks at 10 years after the onset of ocular BD.
    Albrecht von Graæes Archiv für Ophthalmologie 12/2009; 248(5):709-14. · 1.93 Impact Factor
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    ABSTRACT: To analyse clinical outcomes of trabeculectomy with mitomycin C (MMC) in eyes with uveitic glaucoma (UG) with inactive uveitis and compare them to those in eyes with primary open-angle glaucoma (POAG). Retrospective non-randomized comparative interventional case series. A total of 53 eyes with UG and 80 eyes with POAG that received MMC trabeculectomy as an initial ocular surgery with average follow-up of 5.4 years were reviewed retrospectively. The intraocular pressure (IOP) control and persistence of filtering bleb were analysed using the Kaplan-Meier life-table method based on two definitions of successful IOP control, ie complete success (IOP<or=15 mm Hg without anti-glaucoma medications) and qualified success (IOP<or=15 mm Hg with topical anti-glaucoma medications). The incidences of postoperative complications were also examined. Complete success rate for postoperative IOP control at 5 years after trabeculectomy was 57.1+/-7.5% (mean+/-SE) in UG, being comparable to that in POAG (53.7+/-6.1%), and those of qualified success was 64.7+/-7.0 and 65.9+/-5.5% (P=0.60 and 0.53) respectively. Persistence of filtrating blebs was shorter in UG than in POAG (P=0.031). Postoperative inflammation in UG was associated with worse postoperative IOP control and loss of filtering bleb (P=0.027 and 0.021). Postoperative long-standing ocular hypotony was more frequent in UG (P=0.0063). An MMC trabeculectomy for UG with inactive uveitis as an initial ocular surgery had IOP control comparable to that for POAG, suggesting that pre-existing uveitis itself is not a risk factor for failure of a filtering surgery.
    Eye (London, England) 06/2009; 23(7):1509-17. · 1.97 Impact Factor
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    ABSTRACT: We report a case of Candida albicans endophthalmitis with subretinal abscess formation in a patient who underwent liver transplantation. Case report. A 51-year-old Japanese woman complained of deep pain and ciliary injection in her right eye. Three months prior, the patient had undergone liver transplantation for cirrhosis caused by hepatitis C. A slit-lamp examination revealed intense anterior chamber inflammation with hypopyon and fundoscopy showed a yellowish-white subretinal mass lesion in the inferior peripheral fundus. Systemic and topical antibiotics did not prevent further progression of the infection. The patient underwent pars plana vitrectomy treatment three times and a histopathological study of a vitreous specimen revealed C. albicans to be the causative organism. A subretinal abscess, previously reported in Nocardia, Pseudomonas, Staphylococcus, and Aspergillus infection cases, can also occur in patients infected with Candida. Therefore, Candida infection should be considered as a potential cause of subretinal abscess in organ transplant recipients.
    International Ophthalmology 05/2009; 30(2):203-6.
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    ABSTRACT: To visualize retinal ganglion cells (RGCs) and their gradual loss in the living mouse. With the use of B6.Cg-Tg(Thy1-CFP)23Jrs/J mice, which express cyan fluorescent protein (CFP) in RGCs, and a commercially available mydriatic retinal camera attached with a 5 million-pixel digital camera to visualize RGCs in vivo, the authors recorded fundus photographs longitudinally in the ischemia reperfusion model group and the untreated group to evaluate longitudinal changes in the number of RGCs in experimental models. Moreover, RGCs expressing CFP were evaluated histologically by a retrograde-labeling method and retinal whole mount or sections. The authors devised an in vivo imaging technique using a conventional retinal camera and visualized RGCs at the single-cell level. In the ischemia reperfusion model, a longitudinal reduction in the number of RGCs was demonstrated in each mouse eye. The number of RGCs and the fluorescence intensity of the nerve fiber decreased considerably during the first week. The percentages of RGCs decreased to 34.2% +/- 7.5%, 24.1% +/- 9.1%, 23.0% +/- 9.3%, and 22.2% +/- 8.4% (mean +/- SD, n = 5) of the percentages before injury at 1, 2, 3, and 4 weeks after injury, respectively (P < 0.001). In this transgenic mouse, 97% of CFP-expressing cells were RGCs and 73% of RGCs expressed CFP. This in vivo technique allows noninvasive, repeated, and longitudinal evaluation of RGCs for investigation of retinal neurodegenerative diseases and new therapeutic modalities for them.
    Investigative ophthalmology & visual science 08/2008; 49(12):5546-52. · 3.43 Impact Factor
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    ABSTRACT: To investigate the influence of retinal photocoagulation with an indirect ophthalmoscopy contact lens on corneal endothelial cells. Seventeen eyes of 17 patients were evaluated, and corneal endothelial cells were measured twice: just before retinal photocoagulation using an indirect ophthalmoscopy contact lens and 33.2 +/- 10.2 days after surgery. A statistically significant reduction was found in corneal endothelial cell numbers before versus after surgery (P = 0.0003). Our results show corneal endothelial cells to be decreased by retinal photocoagulation with an indirect ophthalmoscopy contact lens. When a patient with a low corneal endothelial cell density receives retinal photocoagulation using an indirect contact lens, it is important to be aware of the potential for further loss.
    Acta Ophthalmologica Scandinavica 07/2007; 85(4):407-8. · 1.85 Impact Factor
  • Japanese Journal of Ophthalmology 01/2007; 51(3):239-40. · 1.27 Impact Factor
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    ABSTRACT: Without Abstract
    Japanese Journal of Ophthalmology 01/2006; 50(1):69-71. · 1.27 Impact Factor
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    ABSTRACT: It is still unknown which metabolite of isopropyl unoprostone is responsible for reducing intraocular pressure. This study was carried out to measure intraocular metabolites of isopropyl unoprostone in the aqueous humor of primate and human eyes. Nine monkeys were randomly divided into three groups, all of which received isopropyl unoprostone. In group I, the drug was scheduled to be instilled at 0 hr, in group II at 1 hr, and in group III at 2 hr, prior to aqueous humor aspiration in order to determine metabolite concentration. Furthermore, 27 patients scheduled for cataract surgery and intraocular lens implantation were divided into five groups that received isopropyl unoprostone. In group A, the drug was scheduled to be instilled at 0 hr, in group B at 1 hr, in group C at 2 hr, in group D at 3 hr, and in group E at 4 hr, prior to surgery. At the beginning of the operation, the aqueous humor was aspirated. Metabolites of isopropyl unoprostone in the aqueous humor were determined by high-performance liquid chromatography. M1 (3-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]propionic acid) (unoprostone free acid) and M2 ((Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]hept-5-enoic acid), an intraocular oxidized metabolite of isopropyl unoprostone, were measured. M1:M2 in monkeys was respectively 0:0 ng/ml in group I, 150.2 +/- 45.1:9.5 +/- 1.7 (p < 0.05) in group II, and 74.6 +/- 31.4:19.2 +/- 5.3 (p < 0.01) in group III. M1:M2 in humans was respectively 0:0 ng/ml in group A, 50.6 +/- 22.3:3.2 +/- 1.3 (p < 0.05) in group B, 125.0 +/- 23.1:12.2 +/- 3.4 (p < 0.001) in group C, 144.9 +/- 33.8:24.5 +/- 6.2 (p < 0.01) in group D, and 56.7 +/- 21.5:18.7 +/- 5.3 (p < 0.05) in group E. A free acid of isopropyl unoprostone is the major intraocular metabolite of isopropyl unoprostone that is expected to act on target tissues in the eyes of both monkeys and humans.
    Current Eye Research 11/2005; 30(10):909-13. · 1.71 Impact Factor
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    Eye 07/2005; 19(6):692-3. · 1.82 Impact Factor
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    ABSTRACT: To prospectively assess the relationship between contraction of the anterior capsule opening and posterior capsule opacification (PCO) after cataract surgery in patients with diabetes mellitus. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Kaiya Eye Clinic, Hamamatsu, and Department of Ophthalmology, Institute of Clinical Medicine, University of Tsukuba, Ibaragi, Japan. This study comprised 45 patients (45 eyes) with diabetes mellitus who had cataract surgery. In all eyes, the anterior capsule opening area and degree of PCO were determined by diaphanoscopy using an anterior eye segment analysis system (EAS-100, Nidek, Inc.) 1 day and 1 year postoperatively. There was no correlation between the size of the anterior capsule opening area 1 day after surgery and the degree of PCO 1 year after surgery (Pearson correlation coefficient [r] = 0.041; P =.79). The percentage reduction in the anterior capsule opening area from 1 day to 1 year after surgery did not correlate with the degree of PCO 1 year after surgery (r = -0.08; P =.60). Contraction of the anterior capsule opening and PCO after cataract surgery cannot be explained by a common mechanism.
    Journal of Cataract and Refractive Surgery 08/2004; 30(7):1517-20. · 2.53 Impact Factor
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    ABSTRACT: To determine the nucleotide sequences of adenovirus (Ad) types 1 and 6 fibre genes; to clarify the molecular basis of the distinct haemagglutination properties of subgenus C Ads and their phylogenetic relations. Human Ad1 and Ad6 fibre genes were sequenced from genomic DNA by direct sequencing. Primer selection was based on alignment of the fibre gene of human Ad serotypes Ad2 and Ad5. Fibre based subgenus C specific polymerase chain reaction (PCR) was performed to check for deletions in field isolates of Ad6, as revealed by sequence analysis of the Ad6 prototype. A phylogenetic tree was constructed from the predicted amino acid (AA) sequences of the fibre gene of important Ads. Ad1 and Ad6 comprise 1746 and 1584 nucleotides, encoding 582 and 528 AA, respectively. Ad6 showed deletions in motifs 15-17 (51 AA) of the shaft when compared with Ad1, Ad2, and Ad5. Subgenus C specific PCR with both prototype and field isolates also showed deletions in Ad6. In the shaft and knob, AA homology was 58.82-72.91% and 68.89-74.59%, respectively. The tail was 100% conserved. Phylogenetically, Ad1 and Ad6, including Ad2 and Ad5, formed a subgenus specific cluster, like other serotypes. The fibre gene (including the knob region) of subgenus C Ads is heterogeneous, providing the molecular basis for lack of crossreactivity in the haemagglutination inhibition test. This heterogeneity could be helpful in fibre based genotyping of subgenus C field isolates. Phylogeny might be useful for subgenus specific identification of important field strains.
    Journal of Clinical Pathology 07/2004; 57(6):612-7. · 2.44 Impact Factor
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    ABSTRACT: To characterise a novel strain of adenovirus (Ad) type Ad8 (genome type Ad8I) involved in an epidemic keratoconjunctivitis (EKC) outbreak in Hiroshima city using serological testing and sequence analysis of the fibre and hexon gene. A neutralisation test (NT) was performed in microtitre plates containing a confluent monolayer of A549 cells using 100 tissue culture infectious doses of virus and type specific antisera. The haemagglutination inhibition test was also carried out in microtitre plates with rat erythrocytes using four haemagglutination units of virus and twofold dilutions of serum. The fibre gene was sequenced by generating overlapping polymerase chain reaction products or by direct sequencing of genomic DNA. Primer selection was based on alignment of the fibre genes of human adenovirus serotypes Ad8, Ad19, Ad37, Ad9, and Ad15 available from Gene Bank. The virus strain was specifically neutralised by anti-Ad8 antibodies, although there was a major crossreaction with anti-Ad9 antibodies. Haemagglutination was equally inhibited by anti-Ad8 and anti-Ad9 antibodies. The predicted amino acid sequences of the hypervariable regions (HVRs) of the Ad8I hexon gene showed higher homology with Ad9 (83.3%) than with Ad8 (62.0%). However, the Ad8I fibre knob was more homologous to Ad8 (94.4%) than to Ad9 (91.6%). Ad8I is a unique strain of adenovirus because of its lower genomic homology with Ad8, major crossreactivity with Ad9 in NT, and mixed genetic organisation of HVRs of the hexon gene. These factors may have enabled the virus to circumvent acquired immunity, resulting in the outbreak.
    Journal of Clinical Pathology 05/2004; 57(4):411-6. · 2.44 Impact Factor
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    ABSTRACT: To compare clinical findings in patients with Behçet's disease (BD) seen in 2 different decades (1980s and 1990s) to determine if there has been a shift toward the appearance of less severe disease. Retrospective, comparative case series. Two hundred forty patients with uveitis caused by BD who had their first visit and at least a 4-month follow-up at the uveitis clinic of University of Tokyo Hospital between January 1980 and December 1999 were enrolled. Patients were divided into 2 groups according to the date of the first visit. The clinical profiles were then compared between the 1980s group (133 patients, observed for 33.5+/-26.4 months) and the 1990s group (107 patients, observed for 46.9+/-32.6 months). Number of ocular attacks per year, visual outcomes, and the percentage of patients who had cyclosporine or cyclophosphamide therapy. Age of onset, type of inflammation, incidence of secondary glaucoma, and surgical history of glaucoma and cataract did not differ between the 1980s and the 1990s. Conversely, in patients in the 1990s, the number of ocular attacks per year and the percentage of patients with cyclosporine or cyclophosphamide therapy decreased significantly. Furthermore, the percentage of eyes with good visual acuity (VA) (?20/30) increased, and the percentage of eyes with poor VA (<20/200) decreased significantly at both the first and the last examinations. There was a trend for less bilateral disease and fewer genital ulcers in the 1990s as well. Through a study of Japanese patients, we confirmed that the clinical outcomes of BD, especially judging by the number of ocular attacks per year and VA, indeed improved during the 1990s.
    Ophthalmology 04/2004; 111(4):810-5. · 5.56 Impact Factor
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    ABSTRACT: Subgenus C human adenoviruses, which include serotypes 1, 2, 5, and 6, are often associated with respiratory illness, ocular infections, gastroenteritis, and systemic infection among immunocompromised patients. To address the problems associated with the conventional typing methods, we developed a fiber-based multiplex PCR assay for simple and specific identification of adenovirus type 1, 2, 5, and 6 field isolates. To design type-specific primers, adenovirus type 1 and 6 fiber genes were sequenced. The assay correctly identified prototype strains of adenovirus serotypes 1, 2, 5, 6, as well as 21 previously typed adenovirus field isolates. Mixing two different prototype DNAs produced two amplicons of different lengths, thus clearly distinguishing the prototypes. The results correlated 100% with serological tests and 95% with the previously described PCR-restriction fragment length polymorphism method. The detection of dual infection is an added benefit of the assay. No nonspecific amplification was detected with other adenovirus serotypes or with nonadenoviral DNA. Our fiber-based multiplex PCR assay will provide a convenient tool for type-specific identification of subgenus C adenovirus isolates in various clinical situations and in epidemiological investigations and is a better alternative than the hexon-based assay.
    Journal of Clinical Microbiology 03/2004; 42(2):670-3. · 4.07 Impact Factor
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    ABSTRACT: To characterise a novel strain (M86) of adenovirus (Ad) involved in epidemic keratoconjunctivitis (EKC). The virus strain was neutralised by antisera to both Ad35 and Ad11. Restriction endonuclease analysis of genomic DNA showed 98% and 88% homology with Ad11 and Ad35, respectively. The deduced amino acid sequence of the hypervariable regions of (HVRs) of the hexon gene showed a higher homology with Ad35 (94.4%) than with Ad11 (83.7%). However, it was 100% homologous to Ad35 in HVRs 1, 2, 3, and 6 and to Ad11 in HVRs 4 and 6. In the fibre knob, the isolate was more homologous to Ad11 (99.4%) than to Ad35 (29.1%). This novel strain of adenovirus showed similarities with both Ad11 and Ad35. The isolation of a novel strain like Ad35+11 is important because of its association with EKC.
    Journal of Clinical Pathology 02/2004; 57(1):95-7. · 2.44 Impact Factor
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    ABSTRACT: The gastrointestinal stromal tumor (GIST) belongs to the leiomyosarcoma or leiomyoma group, and metastasis of leiomyosarcoma to the orbit is extremely rare. The most common sign of the metastasis of leiomyosarcoma to the orbit is proptosis; the primary lesion is usually found in skin or soft tissue. A 60-year-old man, who had a history of multiple metastases of GIST, suffered sudden unilateral blindness. His history and computed tomographic scans suggested that the lesion was a metastasis of GIST to the cavernous sinus around the root of the optic nerve. To the best of our knowledge, this is the first case of metastasis of GIST to the orbit.
    Japanese Journal of Ophthalmology 01/2004; 48(2):166-8. · 1.27 Impact Factor
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    ABSTRACT: To investigate the effects of a new biodegradable dexamethasone drug delivery system, Surodex, in two experimental intraocular inflammation models; endotoxin-induced uveitis (EIU) and experimental autoimmune uveoretinitis (EAU). Surodex was inserted into the right anterior chambers (ACs) of rats. In the EIU experiment, protein concentration, cell infiltration, and myeloperoxidase (MPO) activity in the aqueous humor were measured 24 h after injection. Eyes were evaluated histopathologically. In the EAU experiment, firstly, Surodex was administered at various days after immunization. Then, Surodex was administered on day 9 and eyes were evaluated histopathologically. Intraocular cytokine levels (IFN-gamma and IL-4) were investigated. In the EIU experiments, eyes with Surodex exhibited significantly reduced inflammation compared with contralateral controls. Protein concentrations, cell infiltrations, as well as MPO activity were reduced. In the EAU experiments, all rats with Surodex given on days 0 or 7 showed no or significantly reduced inflammation in both eyes. Rats treated on day 12 developed reduced inflammation only in the treated eyes. IFN-gamma levels were significantly lower in the eyes with Surodex, whereas IL-4 was not detectable. This new, biodegradable corticosteroid drug-delivery system is highly effective in suppressing intraocular inflammation, and should be a useful tool to manage uveitis in humans.
    Albrecht von Graæes Archiv für Ophthalmologie 12/2003; 241(11):927-33. · 1.93 Impact Factor

Publication Stats

530 Citations
128 Downloads
173.35 Total Impact Points

Institutions

  • 2004–2012
    • Tokyo Metropolitan Geriatric Medical Center
      Edo, Tōkyō, Japan
  • 1999–2009
    • University Hospital Medical Information Network
      Edo, Tōkyō, Japan
  • 1994–2009
    • The University of Tokyo
      • Faculty & Graduate School of Medicine
      Edo, Tōkyō, Japan
  • 2003–2004
    • National Institute of Infectious Diseases, Tokyo
      Edo, Tōkyō, Japan