Kazuya Sobue

Nagoya City University, Nagoya, Aichi, Japan

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Publications (75)167.85 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Leptin is a centrally acting hormone that controls metabolic pathways. Recent epidemiological studies suggest that plasma leptin is protective against Alzheimer's disease. However, the mechanism that underlies this effect remains uncertain. To investigate whether leptin inhibits the assembly of amyloid β-protein (Aβ) on the cell surface of neurons, we treated primary neurons with leptin. Leptin treatment decreased the GM1 ganglioside levels in the detergent-resistant membrane microdomains (DRMs) of neurons. The increase of GM1 ganglioside expression induced by leptin was inhibited after pretreatment with inhibitors of phosphatidylinositol 3-kinase (LY294002), Akt (triciribine) and the mammalian target of rapamycin (i.e. rapamycin), but not by an inhibitor of extracellular signal-regulated kinase (PD98059). In addition, pretreatment with these reagents blocked the induction of GM1 ganglioside in DRMs by leptin. Furthermore, Aβ assembly on the cell surface of neurons was inhibited greatly after treatment with leptin. This reduction was markedly inhibited after pretreatment with LY294002, triciribine and rapamycin. These results suggest that leptin significantly inhibits Aβ assembly by decreasing GM1 ganglioside expression in DRMs of the neuronal surface through the PI3K/Akt/mTOR pathway.This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 07/2014; · 3.97 Impact Factor
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    ABSTRACT: Throughout life, new neurons generated in the ventricular-subventricular zone take the long journey to the olfactory bulb. The intracellular mechanisms that precisely control the neurons' migration speed, enabling their well-organized movement, remain unclear. Rho signalling is known to affect the morphology and movement of various cell types, including neurons. Here we identify Gem-interacting protein (Gmip), a RhoA-specific GTPase-activating protein, as a key factor in saltatory neuronal migration. RhoA is activated at the proximal leading process of migrating neurons, where Gmip is also localized and negatively regulates RhoA. Gmip controls the saltatory movement of neurons that regulate their migration speed and 'stop' positions in the olfactory bulb, thereby altering the neural circuitry. This study demonstrates that Gmip serves as a brake for the RhoA-mediated movement of neuronal somata, and highlights the significance of speed control in the well-organized neuronal migration and the maintenance of neuronal circuits in the postnatal brain.
    Nature Communications 01/2014; 5:4532. · 10.02 Impact Factor
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    ABSTRACT: Pathogenesis of Alzheimer’s disease (AD) is characterized by accumulation of extracellular deposits of amyloid β-protein (Aβ) in the brain. The steady state level of Aβ in the brain is determined by the balance between its production and removal; the latter occurring through egress across blood and CSF barriers as well as Aβ degradation. The major Aβ-degrading enzymes in the brain are neprilysin (NEP) and insulin-degrading enzyme (IDE), which may promote Aβ deposition in patients with sporadic late-onset AD. Epidemiological studies have suggested an inverse relationship between the adipocytokine leptin levels and the onset of AD. However, the mechanisms underlying the relationship remain uncertain. We investigated whether leptin is associated with Aβ degradation by inducing NEP and IDE expression within primary cultured astrocytes. Leptin significantly decreased the expression of NEP but not IDE in a concentration- and time-dependent manner through the activation of extracellular signal-regulated kinase (ERK) in cultured rat astrocytes. Furthermore, leptin inhibited the degradation of exogenous Aβ in primary cultured astrocytes. These results suggest that leptin suppresses Aβ degradation by NEP through activation of ERK.
    Biochemical and Biophysical Research Communications 01/2014; · 2.41 Impact Factor
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    ABSTRACT: Percutaneous transtracheal ventilation (PTV) can be life-saving in a cannot ventilate, cannot intubate situation. The aim of this study was to investigate the efficacy of PTV by measuring tidal volumes (VTs) and airway pressure (Paw) in high-flow oxygen ventilation and manual ventilation using a model lung. We examined 14G, 16G, 18G, and 20G intravenous catheters and minitracheotomy catheters. In high-flow oxygen ventilation, the flow was set to 10 L/min, while the inspiratory:expiratory phases (I:E) were 1 s:4 s in the complete upper airway obstruction model and 1 s:1 s in the incomplete obstruction model. In manual ventilation, I:E were 2 s:4 s in the complete obstruction model and 2 s:3 s in the incomplete obstruction model. We ventilated through each catheter for 2 min and measured VT and Paw. In high-flow ventilation, the average VTs were approximately 150 ml and <100 ml with 14G catheters in complete and incomplete upper airway obstruction, respectively. The VTs obtained were reduced when the bore size was decreased. In manual ventilation, the average VTs were over 300 ml and approximately 260 ml with 14G catheters in complete and incomplete upper airway obstruction, respectively. In high-flow ventilation, the airway pressure tended to be higher. The minitracheotomy catheters produced over 800 ml of VT and created almost no positive end-expiratory pressure. High-flow ventilation tends to result in higher airway pressure despite a smaller VT, which is probably due to a PEEP effect caused by high flow.
    Journal of Anesthesia 11/2013; · 0.87 Impact Factor
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    ABSTRACT: Neural stem cells continuously generate new neurons in the ventricular-subventricular zone (V-SVZ) of the postnatal and adult mammalian brain. New neurons born in the rodent V-SVZ migrate toward the olfactory bulb (OB), where they differentiate into interneurons. To reveal novel intracellular molecular mechanisms that control postnatal neuronal migration, we performed a global proteomic search for proteins interacting with Girdin, an essential protein for postnatal neuronal migration. Using GST pull-down and LC-MS/MS shotgun analysis, we identified cytoskeletal proteins, cytoskeleton-binding proteins, and signal-transduction proteins as possible participants in neuronal migration. Our results suggest that Girdin and Girdin-interacting proteins control neuronal migration by regulating actin and/or microtubule dynamics.
    Biochemical and Biophysical Research Communications 11/2013; · 2.41 Impact Factor
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    ABSTRACT: The requisite anesthetic concentration of sevoflurane required to obtain adequate sedation when sufficient analgesics are supplied has not been determined. The purpose of this study was to determine the requisite age-associated concentration of sevoflurane to obtain an adequate level of anesthesia during combined epidural-general anesthesia by bispectral index (BIS) monitoring. Twenty-seven elective abdominal surgery patients (American Society of Anesthesiologists physical status I-II) were enrolled. The patients were divided into two groups of more or less than 60 years of age. We investigated the concentration of sevoflurane required to obtain an adequate sedation level during combined epidural-general anesthesia, maintaining the BIS value between 40 and 60. The requisite sevoflurane concentration required to keep the BIS value at 40-60 was not stable during surgery. In the younger group, the maximum concentration of sevoflurane needed during surgery was 1.95 ± 0.14 (95% confidence interval: 1.87-2.10) vol%, while it was 1.54 ± 0.44 (95% confidence interval: 1.27-1.80) vol% in the older group (P < 0.01). The requisite concentration of sevoflurane required with combined epidural-general anesthesia was 2.5 vol% for the younger group and 2.0 vol% for the older group as determined by BIS monitoring. We believe that these percentages are sufficient to avoid awareness during surgery with adequate analgesia.
    Korean journal of anesthesiology 06/2013; 64(6):489-93.
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    ABSTRACT: Pathological accumulation of cortical amyloid β-protein (Aβ) is an early and consistent feature of Alzheimer's disease (AD). Aβ levels in the brain are determined by production and catabolism. Previous studies have suggested that deficits in the brain expression of neprilysin (NEP) and the insulin-degrading enzyme (IDE), which are both proteases involved in amyloid degradation, may promote Aβ deposition in patients with sporadic late-onset AD. Because the incidence of AD increases after surgical intervention, we examined whether ketamine, which is a general anaesthetic with neuroprotective properties for excitotoxic ischemic damage, is associated with Aβ degradation by inducing NEP and IDE expression. The non-competitive N-methyl-D-aspartate receptor antagonist ketamine and MK801 significantly decreased the expression of NEP, but not IDE, in a concentration- and time-dependent manner through the dephosphorylation of p38 mitogen-activated protein kinase (MAPK) in cultured rat astrocytes. Furthermore, NEP-reduced reagents significantly suppressed the degradation of exogenous Aβ in cultured astrocytes. These results suggested that ketamine suppresses the Aβ degradation of NEP by reducing p38 MAPK-mediated pathway activity.
    Neuroscience Letters 04/2013; · 2.03 Impact Factor
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    ABSTRACT: BACKGROUND:: The incidence of Alzheimer disease may increase after surgical interventions. Amyloid β-protein (Aβ) fibrillogenesis, which is closely related to Alzheimer disease, is reportedly accelerated by exposure to anesthetics. However, the effects of GM1 ganglioside (GM1) on Αβ fibrillogenesis have not yet been reported. The current study was designed to examine whether the anesthetics propofol and thiopental are associated with Αβ assembly and GM1 expression on the neuronal cell surface. METHODS:: PC12N cells and cultured neuronal cells were treated with propofol or thiopental, and GM1 expression in treated and untreated cells was determined by the specific binding of horseradish peroxidase-conjugated cholera toxin subunit B (n = 5). The effects of an inhibitor of the γ-aminobutyric acid A receptor was also examined (n = 5). In addition, the effects of the anesthetics on GM1 liposome-induced Αβ assembly were investigated (n = 5). Finally, the neurotoxicity of the assembled Αβ fibrils was studied by the lactate dehydrogenase release assay (n = 6). RESULTS:: Propofol (31.2 ± 4.7%) and thiopental (34.6 ± 10.5%) decreased GM1 expression on the cell surface through the γ-aminobutyric acid A receptor. The anesthetics inhibited Αβ fibril formation from soluble Αβ in cultured neurons. Moreover, propofol and thiopental suppressed GM1-induced fibril formation in a cell-free system (propofol, 75.8 ± 1.9%; thiopental, 83.6 ± 1.9%) and reduced the neurotoxicity of a mixture containing Aβ and GM1 liposomes (propofol, 35.3 ± 16.4%; thiopental, 21.3 ± 11.6%). CONCLUSIONS:: Propofol and thiopental have direct and indirect inhibitory effects on Αβ fibrillogenesis.
    Anesthesiology 02/2013; · 5.16 Impact Factor
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    ABSTRACT: Dexmedetomidine (Dex) is a selective central α2-agonist with anesthetic properties and has been used in clinical practice for sedation in the intensive care unit (ICU) after operations. In this study, an analytical assay for the determination of Dex in a small amount of plasma was developed for the application to pediatric ICU trials. The quantification of Dex was constructed using the original stable isotope Dex-d(3) for electrospray ionization-tandem mass spectrometry (ESI-MS/MS) in the selected reaction monitoring mode. A rapid ultra-performance liquid chromatography technique was adopted using ESI-MS/MS with a runtime of 3 min. Efficacious concentration levels (50 pg/mL to 5 ng/mL) could be evaluated using a very small amount of plasma (10 μL) from patients. The lower limit of the quantification was 5 pg/mL in the plasma (100 µL). For sample preparation, a solid-phase extraction was used along with the OASIS-HLB cartridge type. Recovery values ranged from 98.8 to 100.3% for the intra- [relative standard deviation (RSD), 0.9-1.3%] and inter- (RSD, 0.9-1.5%) day assays. A stable test had recovery values that ranged from 97.8 to 99.7% with an RSD of 1.0-1.9% for the process/wet extract, bench-top, freeze-thaw and long-term tests. This method was used to measure the Dex levels in plasma from pediatric ICU patients. In the clinical ICU trial, the small amount of blood (approximate plasma volume, 200 μL) remaining from blood gas analysis was reused and targeted for the clinical analysis of Dex in plasma. Copyright © 2013 John Wiley & Sons, Ltd.
    Biomedical Chromatography 02/2013; · 1.95 Impact Factor
  • Hiroki Yamauchi, Shoji Ito, Kazuya Sobue
    Masui. The Japanese journal of anesthesiology 11/2012; 61 Suppl:S159-64.
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    ABSTRACT: A woman with complex regional pain syndrome (CRPS) in the right lower extremity who wished to discontinue medications to get pregnant underwent implantation of a spinal cord stimulation system (SCS). An electrode lead was placed at Th(10-11) in the epidural space, accessed via the L(2-3) interspace with a paramedian approach, and a pulse generator was implanted in the left buttock. She kept the SCS on 24 h a day. After she had experienced several chemical abortions, finally she got pregnant via artificial insemination. She had an uneventful delivery of a healthy baby by cesarean resection under spinal anesthesia. In a patient with CRPS who has an implanted SCS system and wishes to get pregnant, the electrode lead into the low thoracic epidural space should be accessed via the high lumbar intervertebral space in consideration of a future requirement for spinal or epidural anesthesia for cesarean section. The generator should be placed in the buttock to prevent impairment of the SCS system being caused by the enlarged abdomen during pregnancy. Although we were apprehensive of adverse effects owing to the electromagnetic field force and change of blood flow in the pelvic viscera, our patient had a successful delivery. SCS is a favorable option for patients with CRPS who wish to get pregnant.
    Journal of Anesthesia 08/2012; · 0.87 Impact Factor
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    ABSTRACT: Perinatal hypoxia-ischemia (HI) frequently causes white-matter injury, leading to severe neurological deficits and mortality, and only limited therapeutic options exist. The white matter of animal models and human patients with HI-induced brain injury contains increased numbers of oligodendrocyte progenitor cells (OPCs). However, the origin and fates of these OPCs and their potential to repair injured white matter remain unclear. Here, using cell-type- and region-specific genetic labeling methods in a mouse HI model, we characterized the Olig2-expressing OPCs. We found that after HI, Olig2+ cells increased in the posterior part of the subventricular zone (pSVZ) and migrated into the injured white matter. However, their oligodendrocytic differentiation efficiency was severely compromised compared with the OPCs in normal tissue, indicating the need for an intervention to promote their differentiation. Erythropoietin (EPO) treatment is a promising candidate, but it has detrimental effects that preclude its clinical use for brain injury. We found that long-term postinjury treatment with a nonerythropoietic derivative of EPO, asialo-erythropoietin, promoted the maturation of pSVZ-derived OPCs and the recovery of neurological function, without affecting hematopoiesis. These results demonstrate the limitation and potential of endogenous OPCs in the pSVZ as a therapeutic target for treating neonatal white-matter injury. STEM Cells2012;30:2234-2247.
    Stem Cells 08/2012; 30(10):2234-47. · 7.70 Impact Factor
  • Journal of Anesthesia 06/2012; · 0.87 Impact Factor
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    ABSTRACT: The American Society of Anesthesiologists (ASA) published a clinical practice guideline of preoperative fasting in 1999. A nationwide survey conducted in Japan in 2003 reveals that many hospitals have a much longer fasting period. We conducted a similar survey in three limited areas in Japan to assess the changes in fasting practice. A written questionnaire for preoperative fasting was sent to 50 hospital in 3 prefectures. The duration of fasting for liquids tends to be shorter than those in the 2003 survey. The rates of application of the ASA guideline, however, are still low specifically in adults (4.2%), which is significantly lower than those in children (17.7%), or in infants (39.0%). The reasons for noncompliance are mainly due to organizational problems associated with scheduling of operation. Most hospitals aspire to have Japanese guideline about preoperative fasting periods. Longer preoperative fasting periods are still common practice in Japanese hospitals.
    Masui. The Japanese journal of anesthesiology 06/2012; 61(6):643-8.
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    ABSTRACT: Type 2 diabetes mellitus is thought to be a significant risk factor for Alzheimer's disease. Insulin resistance also affects the central nervous system by regulating key processes, such as neuronal survival and longevity, learning and memory. However, the mechanisms underlying these effects remain uncertain. To investigate whether insulin resistance is associated with the assembly of amyloid β-protein (Aβ) at the cell surface of neurons, we inhibited insulin-signalling pathways of primary neurons. The treatments of insulin receptor (IR)-knockdown and a phosphatidylinositol 3-kinase inhibitor (LY294002), but not an extracellular signal-regulated kinase inhibitor, induced an increase in GM1 ganglioside (GM1) levels in detergent-resistant membrane microdomains of the neurons. The aged db/db mouse brain exhibited reduction in IR expression and phosphorylation of Akt, which later induced an increase in the high-density GM1-clusters on synaptosomes. Neurons treated with IR knockdown or LY294002, and synaptosomes of the aged db/db mouse brains markedly accelerated an assembly of Aβs. These results suggest that ageing and peripheral insulin resistance induce brain insulin resistance, which accelerates the assembly of Aβs by increasing and clustering of GM1 in detergent-resistant membrane microdomains of neuronal membranes.
    Journal of Neurochemistry 01/2012; 121(4):619-28. · 3.97 Impact Factor
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    ABSTRACT: Respiratory management for patients with a giant bulla during anesthesia should avoid positive-pressure ventilation to reduce the risk of barotraumas. We report a case of anesthetic management of a 42-year-old man with a giant bulla who had an elective surgery for biopsy of a tumor on his left elbow. Balanced anesthesia consisting of general anesthesia was given under spontaneous breathing combined with interscalene brachial plexus blockade for intra- and postoperative analgesia for the elbow surgery. The patient was monitored by electrocardiography, non-invasive arterial pressure, SpO2, endtidal CO2 tension and bispectral index. Ultrasound-guided interscalene block was performed with the patient awake. After injection of 0.75% ropivacaine 20 ml and 1% lidocaine 16 ml for brachial plexus block, general anesthesia was induced with a bolus of fentanyl 100 microg to reduce cough reflex and propofol using target control infusion with a 2 microg x ml(-1) plasma concentration. The airway was maintained with a size 4 LMA-Proseal, which was inserted with care under spontaneous breathing. There were no serious complications such as pneumothorax in perioperative period. We performed successful anesthetic management, without any complications, combined with interscalene brachial plexus block and spontaneous breathing in a patient with a giant bulla.
    Masui. The Japanese journal of anesthesiology 09/2011; 60(9):1101-3.
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    ABSTRACT: Inflammatory or oxidative stress is related to various diseases, including not only inflammatory diseases, but also diabetes, cancer, and atherosclerosis. The aim of this study was to evaluate the anti-inflammatory effects of a new enteral diet, MHN-02, which contains abundant antioxidants and whey peptide. The study also investigated the ability of MHN-02 to attenuate lethality, liver injury, the production of inflammatory cytokines, and the production of oxidized products using a carbon tetrachloride-induced rat model of severe fulminant hepatitis. Male Sprague-Dawley rats were fed either a control diet or the MHN-02 diet for 14 days and injected with 2 mL/kg of carbon tetrachloride. Survival of rats was monitored from day 0 to day 3. To evaluate liver injury, inflammation, and oxidative stress, blood and liver samples were collected, and aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, interleukin 6, tumor necrosis factor-α, and superoxide dismutase activity as a free radical scavenger were measured. A portion of the liver was evaluated histologically. The survival rates of rats receiving the MHN-02 diet and the control diet were 90% and 55%, respectively. In the MHN-02 diet group, levels of serum liver enzymes and serum cytokines were significantly lower than in the control group. Superoxide dismutase activity in the MHN-02 diet was significantly higher in the MHN-02 group. Pathological lesions were significantly larger in the control group. Supplementation of enteral diets containing whey peptide and antioxidants may protect against severe hepatitis.
    Journal of Parenteral and Enteral Nutrition 07/2011; 35(4):516-22. · 2.49 Impact Factor
  • Anaesthesia and intensive care 07/2011; 39(4):767-8. · 1.40 Impact Factor
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    ABSTRACT: End-tidal P(CO(2)) (Pe'(CO(2))) is routinely used in the clinical assessment of the adequacy of ventilation because it provides an estimate of Pa(CO(2)). How well Pe'(CO(2)) reflects Pa(CO(2)) depends on the gradient between them, expressed as ΔPa-e'(CO(2)). The major determinant of ΔPa-e'(CO(2)) is alveolar dead space (Vd(alv)). The fraction of inspired O(2) (Fi(O(2))) is not thought to substantially affect ΔPa-e'(CO(2)) in anaesthetized patients. We hypothesized that a high Fi(O(2)) may indeed increase ΔPa-e'(CO(2)) by preferentially vasodilating well-perfused alveoli, resulting in the redistribution of blood flow to these alveoli from poorly perfused alveoli and an increase in Vd(alv). We therefore investigated the effects of changes in Fi(O(2)) on ΔPa-e'(CO(2)) and Vd(alv). With Institutional Review Board approval and informed consent, we studied 20 ASA I-II supine patients undergoing elective lower abdominal surgery under combined general and epidural anaesthesia. At constant levels of ventilation, Fi(O(2)) levels of 0.21, 0.33, 0.5, 0.75, and 0.97 were applied in a random order and ΔPa-e'(CO(2)) and Vd(alv) were calculated. The ΔPa-e'(CO(2)) values were, in order of ascending Fi(O(2)), {mean [standard error of the mean (SEM)]} 0.13 (0.04), 0.28 (0.08), 0.29 (0.09), 0.44 (0.11), and 0.53 (0.09) kPa. The corresponding values of Vd(alv) were 25.5, 33.8, 35.8, 48.9, and 47.4 ml. Each successive hyperoxic level showed a significant increase in ΔPa-e'(CO(2)) except between the 0.33-0.5 and 0.75-0.97 Fi(O(2)) levels. These data demonstrate that ΔPa-e'(CO(2)), in anaesthetized patients depends on Fi(O(2)).
    BJA British Journal of Anaesthesia 06/2011; 107(4):631-5. · 4.24 Impact Factor
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    ABSTRACT: Cardiac tamponade is a serious complication of central venous catheter (CVC) insertion. The position of the carina has been shown to be near the pericardial reflection and can easily be identified as a landmark on routine chest x-ray (CXR). The purpose of this study was to show a simple way to predict optimal CVC depth, thereby facilitating safe positioning of the CVC tip. Subjects included 119 inpatients undergoing gastroenterologic surgery. Central venous catheterization was performed through the right internal jugular vein or the right subclavian vein. The insertion depth was measured. Postoperatively, the CVC tip position was confirmed by CXR and the distance between the CVC tip and the carina was measured. We compared the "original measurement" up to the carina from the insertion point with the "calculated measurement" derived by adding half the length of the right clavicle and the vertical length between the sternal head of the right clavicle and the carina on the CXR. There was a significant correlation between the original measurement and the calculated measurement when performed through the internal jugular vein and the subclavian vein. The appropriate length of CVC inserted through the right internal jugular vein or right subclavian vein could be estimated by the calculated measurement of adding half the length of the right clavicle and the vertical length between the sternal head of the right clavicle and the carina.
    Nutrition 10/2010; 27(5):557-60. · 2.86 Impact Factor

Publication Stats

678 Citations
167.85 Total Impact Points

Institutions

  • 1998–2014
    • Nagoya City University
      • • Department of Ansthesiology and Medical Crisis Management
      • • Department of Developmental and Regenerative Biology
      • • Department of Molecular Neurobiology
      • • Department of Neurosurgery (Hospital)
      Nagoya, Aichi, Japan
  • 2013
    • Ritsumeikan University
      • College of Pharmaceutical Sciences
      Kyoto, Kyoto-fu, Japan
  • 2002
    • Nagoya University
      • Division of Anesthesiology
      Nagoya-shi, Aichi-ken, Japan