遺伝学的、光遺伝学的手法を用いた、ラットにおける脳機能局在性の研究

学位の種別:課程博士University of Tokyo(東京大学

First multicenter survey on infectious keratitis following excimer laser surgery in Japan

AbstractPurposeTo report the first multicenter survey in Japan on infectious keratitis after excimer laser surgery.MethodsThe laser in situ keratomileusis (LASIK) Safety Network (LSN) Committee sent questionnaires to 28 LSN member hospitals to assess the total number of laser corneal surgeries, the number of infection cases (including suspicious cases), and the postoperative follow-up rate during a 3-year period.ResultsResponses were obtained from 27 (96.4%) of 28 institutions. One phototherapeutic keratectomy infection case was reported among 22,415 excimer laser surgery cases, which equates to an incidence rate of 0.004%. The follow-up rate was 94.14% (67.2–100%), 80.11% (41.0–96.1%), 57.95% (11.5–93.0%), and 46.64% (4.7–93.0%) at 1 month, 3 months, 6 months, and 12 months of follow-up, respectively.ConclusionInfectious keratitis is a potentially devastating complication of excimer laser surgery. We did not see any infectious keratitis for refractive cases. This first multicenter survey in Japan on infectious keratitis provides important information on the safety of this therapy

A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details

IgG4-related disease (IgG4RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. IgG4RD may be present in a certain proportion of patients with a wide variety of diseases, including Mikulicz’s disease, autoimmune pancreatitis, hypophysitis, Riedel thyroiditis, interstitial pneumonitis, interstitial nephritis, prostatitis, lymphadenopathy, retroperitoneal fibrosis, inflammatory aortic aneurysm, and inflammatory pseudotumor. Although IgG4RD forms a distinct, clinically independent disease category and is attracting strong attention as a new clinical entity, many questions and problems still remain to be elucidated, including its pathogenesis, the establishment of diagnostic criteria, and the role of IgG4. Here we describe the concept of IgG4RD and up-to-date information on this emerging disease entity

Optogenetic Manipulation of Cerebellar Purkinje Cell Activity In Vivo

Purkinje cells (PCs) are the sole output neurons of the cerebellar cortex. Although their anatomical connections and physiological response properties have been extensively studied, the causal role of their activity in behavioral, cognitive and autonomic functions is still unclear because PC activity cannot be selectively controlled. Here we developed a novel technique using optogenetics for selective and rapidly reversible manipulation of PC activity in vivo. We injected into rat cerebellar cortex lentiviruses expressing either the light-activated cationic channel channelrhodopsin-2 (ChR2) or light-driven chloride pump halorhodopsin (eNpHR) under the control of the PC-specific L7 promoter. Transgene expression was observed in most PCs (ChR2, 92.6%; eNpHR, 95.3%), as determined by immunohistochemical analysis. In vivo electrophysiological recordings showed that all light-responsive PCs in ChR2-transduced rats increased frequency of simple spike in response to blue laser illumination. Similarly, most light-responsive PCs (93.8%) in eNpHR-transduced rats decreased frequency of simple spike in response to orange laser illumination. We then applied these techniques to characterize the roles of rat cerebellar uvula, one of the cardiovascular regulatory regions in the cerebellum, in resting blood pressure (BP) regulation in anesthetized rats. ChR2-mediated photostimulation and eNpHR-mediated photoinhibition of the uvula had opposite effects on resting BP, inducing depressor and pressor responses, respectively. In contrast, manipulation of PC activity within the neighboring lobule VIII had no effect on BP. Blue and orange laser illumination onto PBS-injected lobule IX didn't affect BP, indicating the observed effects on BP were actually due to PC activation and inhibition. These results clearly demonstrate that the optogenetic method we developed here will provide a powerful way to elucidate a causal relationship between local PC activity and functions of the cerebellum

Data from: An automated platform for high-throughput mouse behavior and physiology with voluntary head-fixation

Recording neural activity during animal behavior is a cornerstone of modern brain research. However, integration of cutting-edge technologies for neural-circuit analysis with complex behavioral measurements poses a severe experimental bottleneck for researchers. Critical problems include a lack of standardization for psychometric and neurometric integration, and lack of tools that can generate large, sharable datasets for the research community in a time and cost effective way. Here, we introduce a novel mouse behavioral-learning platform featuring voluntary head fixation and automated high throughput data collection for integrating complex behavioral assays with virtually any physiological device. We provide experimental validation by demonstrating behavioral training of mice in visual discrimination and auditory detection tasks. To examine facile integration with physiology systems, we coupled the platform to a two-photon microscope for imaging of cortical networks at single-cell resolution. Our behavioral learning and recording platform is a prototype for the next generation of mouse cognitive studies

Change in body weight of mothers and neonates and in milk composition during denning period in captive Japanese black bears (Ursus thibetanus japonicus)

Japanese black bears, Ursus thibetanus japonicus, have been classified as a vulnerable species so that data on reproduction are needed to maintain and/or extend their population. They are known to have a peculiar style of reproduction, giving birth to their neonates and raising them during denning, a period of complete fasting. In this study, we investigated the metabolic rate and milk composition of mother bears raising neonates, and the changes in body weight of the neonates under captive conditions. Seven female bears kept in dens were weighed once a month, and the amount of energy they used was calculated. From birth, cubs were also weighed and their growth rate was determined. In addition, the milk composition was analyzed to investigate its characteristics. As a result, it was found that mother bears used 34% more energy than did solitary females. There was no significant difference in the energy used for nursing whether they had single or twin cubs. On the other hand, the body weight gain of single cubs was significantly higher than that of twin cubs, suggesting that the growth of the cubs was highly affected by the suppression of mother's energy consumption during the fasting period. The milk had high fat and low sugar concentrations. This indicates that mother bears used the fat accumulated prior to denning for their main energy source when raising cubs. Considering all results together, Japanese black bears showed remarkable efficiency in the use of energy for reproduction during the fasting period

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Assessment of quality of life in patients with visual impairments using a new visual function questionnaire: The VFQ-J11

Background: The purpose of the present study was to assess the vision-related quality of life (QOL) of visually impaired patients using the Japanese 11-item National Eye Institute Visual Function Questionnaire (VFQ-J11). Comparisons with the 25-item version (VFQ-25) and the EuroQoL Index using a large group of patients with various degrees of impairments and various causative diseases were performed. Methods: A total of 232 visually impaired Japanese patients were recruited from six ophthalmology departments in Japan. Information on ophthalmic findings and patient backgrounds was collected, and information on QOL and utility assessments was collected from the patients by means of survey questionnaires. Results: The average age of patients was 69.6±14.3 years. Both the vision-related QOL scores (VFQ-25 composite and VFQ-J11) were significantly associated with better and worse visual acuity (VA) in visually impaired subjects (all P<0.01). VFQ-J11 was comparable to VFQ-25 regardless of causative diseases. VFQ-25 composite and the VFQ-J11 scores were concurrently associated with a range of systemic medical disorders. EuroQoL Index had a significant association with better eye VA (P<0.01), but not with worse eye VA, or any systemic disorders. Conclusion: VFQ-J11 provides valid data on vision-related QOL and is less of a burden for patients with vision problems