departmental bulletin paper

Application of cell therapy using stem cell into intractable diseases has been noted as the medicine in the next generation taking the place of organ transplantation. Bone marrow cells have been focused as a candidate of the source of this therapy. Liver failure is a terminal state of all advanced liver diseases and thousands of patients are dying of decompensated liver cirrhosis in every year in Japan. Liver transplantation must be the strongest weapon to relieve those patients. However, particularly in Japan, liver transplantation has not been popularized. In this sense, we thought of autologous bone marrow cells transplantation for decompensated liver cirrhosis. Basic studies using animal model revealed that transplanted bone marrow cells into syngenic mouse suffering from liver cirrhosis migrated into the damaged liver and transdifferentiated to the hepatocytes. Based upon the animal studies, clinical trial of this new cell therapy supported by the Ministry of Health, Labor and Welfare is ongoing. It is early to estimate this therapy. However, free from liver failure has been observed in some cases.

In this study, as one solution to the problem for condition assessment of existing short- and medium-span reinforced/prestressed concrete bridges, a new monitoring method using a public bus as part of a public transit system (bus monitoring system) is proposed, along with safety indices, namely, characteristic deflection, which is relatively free from the influence of dynamic disturbances due to such factors as the roughness of the road surface, and a structural anomaly parameter. A basic study was conducted by using the results of technical verification experiments and numerical analysis simulation. This paper describes the details of not only how to assess the bridge condition by public bus vibration measured in operating on Ube City bus network as a specific example for verify the system but also what kind of consideration we need to apply the system to existing bridges in overseas country. And, the degrees of abnormality of the monitored bridges were expressed with the "inspection necessity level" to enable local governments to prioritize their bridge maintenance needs quantitatively.

In this study, a novel VR-based system for inspection of deteriorating concrete bridges is proposed to support of the crack and spalling detection which is a key role in existing bridge maintenance. The proposed system, called a VR-based support system for bridge inspection, was applied to an aged bridge for confirming the representing ability of both cracking and spalling damages as a specific example. Experimental results showed that the VR images data with hammering sounds (audio) data have a sufficient ability of representing both crack width over 0.2 mm and a certain spalling area near concrete surface. In this system, the three-dimensional image(photo) data was used to recognize the cracking damage for professional visual inspector. On the other hand, as spalling damage inside the concrete surface couldn’t be identified accurately from only image(photo) data, then the hammering sounds (audio) data was incorporated into the system as an additional function for recoginittion of the spalling damage.

This paper describes the methods of performance evaluation and remaining life prediction for an aged reinforced concrete (RC) T-girder bridge via visual inspection data. The Bridge Management System (J-BMS) that was previously developed by the authors, and which is capable of forecasting the deterioration process of existing bridge members, was applied to evaluate the safety indices (soundness score) and re-maining life of the target bridge based on these test results. Using these methods, the remaining life of an aged RC-T girder bridge(SK-bridge) can be quantitatively estimated by applying the bridge rating expert (BREX) system, which is a subsystem of the J-BMS RC version that incorporates with the field inspection data. In this study, visual inspection was carried out on the aged bridge(SKbridge) by professional visual inspectors, during which all variations of the inspection results were evaluated using a five-step question-naire. As a result, it was found that the soundness score (safety index) and remaining life predictions were influenced by the learning (supervised) data selection. Additionally, the predicted remaining lives were verified through concrete core tests extracted from main girders and deck slabs, and cross-section cutting-off girder tests.

Largest portion of the bridge stock in almost any country and bridge owning organisation consists on ordinary bridges that has short or medium spans and are now deteriorating due to aging, etc. Therefore, it is becoming an important social concern to develop and put to practical use simple and efficient health monitoring systems for existing short and medium span (10-30m) bridges. In this paper, one practical solution to the problem for condition assessment of short and medium span bridges was discussed. A vehicle-based measurements with a public bus as part of a public transit system (called "Bus monitoring system") has been developed to capable of detecting damage that may affect the structural safety of a bridge from long term vibration measurement data collected while the vehicle (bus) crossed the target bridges. This paper systematically describes how the system has been developed. The bus monitoring system aims to detect the transition from the damage acceleration period, in which the structural safety of an aged bridge declines sharply, to the deterioration period by continually monitoring the bridge of interest. To evaluate the practicality of the newly developed bus monitoring system, it has been fieldtested over a period of about four years by using an in-service fixed-route bus operating on a bus route in the city of Ube, Yamaguchi Prefecture, Japan. The verification results thus obtained are also descrived in this paper. This study also evaluates the sensitivity of “characteristic deflection”, which is a bridge (health) condition indicator used by the bus monitoring system, in damage detection. Sensitivity of “characteristic deflection” is verified by introducing artificial damage into a bridge that has ended its service life and is awaiting removal.

This paper introduces an approach to the realization of an ICT-based bridge remote monitoring system which enables real-time monitoring and control for unexpected heavy loads such as big earthquake and strong typhoon. In this paper, the integrated bridge remote monitoring system called the “Intelligent Bridge” consists of a stand-alone monitoring system (SMS) and a web-based internet monitoring system (IMS) for bridge maintenance but also its application to para-stressing bridge system as an intelligent structure. For the purpose of verifying its validity to actual bridge structure, an attempt is made to study the possibility of controlling the actual structural performance by adjusting the cable forces on a 2-span continuous cable-stayed bridge model. The experimental results demonstrate that the implemented monitoring system supplies detailed and accurate information about bridge behavior for further evaluation and diagnosis, and it also opens up prospects for future application of web-based remote system to actual in-service bridges under field conditions.

Aim: To evaluate the efficacy of quantitative analysis for differentiating pancreatic ductal adenocarcinoma (PDAC) and inflammatory pancreatic masses (IPM) using time intensity curve (TIC) analysis based on contrast-enhanced endoscopic ultrasonography (CE-EUS). Methods: We reviewed 89 patients who had undergone CE-EUS for pancreatic solid lesions at our department between August 2012 and January 2016. CE-EUS images were recorded for 2 minutes after injection of the contrast agent. The diagnostic abilities of the enhanced patterns and TIC analysis were assessed. Results: The enhanced patterns of PDAC were mainly hypovascular and heterogeneous (66/77), while IPM were mainly isovascular and homogeneous (6/12). In PDAC, sensitivity was 77.9%, specificity 83.3%, and accuracy was 78.7%. In TIC analysis, the intensity reduction rate was significantly different at 10 and 30 seconds after peak intensity. After creating a cutoff value (49%) based on the receiver operating characteristic curve for the intensity reduction rate after 30 seconds, diagnosing PDAC with TIC analysis had a sensitivity of 67.5%, specificity of 100%, and accuracy of 71.9%. Combining enhanced pattern analysis with TIC analysis had a sensitivity of 90.9%, pecificity of 83.3%, and accuracy of 89.9%. Conclusion: Combining TIC analysis with CE-EUS improved diagnostic accuracy when differentiating between PDAC and IPM.

Aberrant increases in protein phosphatase 1(PP1) activity have been shown to be associated with inefficient sarcoplasmic reticulum Ca^{2+} cycling, leading to cardiac dysfunction in the failing heart. In the present study, we investigated whether BNP promoter-inducible suppression of PP1β would ameliorate progression of pressure overload-induced heart failure in mice, a clinically relevant animal model. An Adeno-associated virus 9 (AAV9) vector encoding PP1βshRNA and a negative control (NC) shRNA driven by a brain natriuretic peptide (BNP) promoter with an emerald green fluorescent protein expression (EmGFP) cassette were used to test the hypothesis. AAV9 vectors (AAV9-BNP-EmGFP-PP1βshRNA and AAV9-BNP-EmGFP-NCshRNA) were introduced into the in vivo heart via the tail vein injection (4x10^{11} GC/mice) in 8-week-old C57BL6J mice, followed by transverse aortic constriction (TAC) 2 weeks after the AAV9 vector injection. Post TAC cardiac function was sequentially assessed every 2 week by echocardiography, followed by hemodynamic assessment at 1 month. AAV9-BNP-EmGFP-PP1βshRNA treatment suppressed myocardial PP1β expression by 15% compared with the NCshRNA group (p<0.001). The fractional shortening (%FS) of the left ventricle in the PP1βshRNA-treated group was significantly larger than the NCshRNA-treated group (21%±1.0% vs. 15%±0.01, p<0.01). The ratios of heart weight (HW) / body weight (BW) and lung weight (LW) / BW in the PP1βshRNA group were significantly smaller than those of the NCshRNA group (HW/BW: 9.20±0.49 vs. 10.6±0.45 mg/g

Background: Angiotensin II (AngII) increases reactive oxygen species (ROS) and induces glomerular sclerosis. Toll-like receptor 4 (TLR4)-mediated inflammation enhances the renal impairment in renal inflammatory diseases. The relationship between TLR4 and AngII-induced glomerular sclerosis is unknown.Methods: Mice lacking TLR4 function (Tlr4^{lps-d}) and wild-type (WT) mice were randomized into groups treated with AngII, norepinephrine (NE) or a sub-depressor dose of the AngII receptor blocker irbesartan along with AngII for 2 weeks. We then assessed the expressions of NADPH oxidase and monocyte chemoattractant protein-1 (MCP-1) and the inflammatory cell recruitment in the glomeruli. We also evaluated the mesangial matrix proliferation and ROS.Results: AngII and NE equally increased the systolic blood pressure compared to the control mice (p<0.05). In the WT mice treated with AngII, we observed glomerular sclerosis, an increase in NADPH oxidase, MCP-1 and the infiltration of macrophages as well as ROS content in the glomeruli compared to the control mice (p<0.05), whereas the Tlr4^{lps-d} mice showed little effects of AngII on these indices. In addition, the sub-depressor-dose irbesartan treatment reversed these changes. NE had little effects on these indices. Conclusions: TLR4 plays an important role in AngII-induced oxidative stress, inflammation and glomerular sclerosis through the AT1 receptor.

Aims: To clarify the usefulness of preservative-free ophthalmic preparations equipped with a filter. Methods: A total of 1,615 samples of in-use ophthalmic preparations were examined for microbial contamination. Results: Of 1,094 samples of preservative-containing ophthalmic preparations, 31 (2.8%) showed microbial contamination. Of 289 samples of preservative-free ophthalmic preparations without a filter, 6 (2.1%) were contaminated, consisting of 4 (13.8%) of 29 samples of hospital preparations and 2 (0.8%) of 260 samples of commercially available new quinolone antimicrobial agents. On the other hand, the microbial contamination rate in preservative-free ophthalmic preparations equipped with a filter was 0% (0 of 232 samples).The major contaminants detected in these preservative-containing ophthalmic preparations and preservative-free ophthalmic preparations without a filter were glucose-nonfermentative Gram-negative bacilli such as Pseudomonas fluorescens, Acinetobacter spp., and P. aeruginosa, coagulase (-) staphylococci, and Candida spp. The contaminant level was 10-99 colony forming units (CFU)/mL in 37.8% (14 of 37 samples), and 10^2 - 10^6 CFU/mL in 62.2% (23 of 37 samples). Conclusions: Preservative-free ophthalmic preparations equipped with a filter not only have zero risk of the oculotoxic effects of preservatives, but are also safe in terms of their lack of microbial contamination.

We investigated the relationship between myocardial oxidative stress and cardiac sympathetic hyperactivity in patients with takotsubo cardiomyopathy (TC) compared with acute anteroseptal myocardial infarction (AMI). Methods: In 10 TC patients and 10 AMI patients, electrocardiogram, echocardiography, cardiac catheterization were conducted, and plasma catecholamines and urinary (U) 8-hydroxy-2’-deoxyguanosine (8-OHdG) as a marker of oxidative DNA damage were taken for one week from onset. Results: On admission, the coronary sinus (CS) had significantly higher norepinephrine (NE) and 8-OHdG levels than the aortic root (Ao) and peripheral blood vessels. Circulating catecholamines in TC patients tended to be higher than those in AMI patients

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by stress- or exercise- induced ventricular tachycardia, frequently leading to sudden cardiac death. A considerable body of evidence accumulated over recent years suggests that mutation-linked cardiac ryanodine receptor (RyR2) defects cause Ca^2+ leak from sarcoplasmic reticulum, which triggers delayed afterdepolarization and leads to CPVT. However, the underlying mechanism, by which a single mutation in such a large molecule causes drastic effects on the channel function, remains elusive. Here we report that introduction of a human CPVT mutation S2246L into the mouse RyR2 induces aberrant activation of channel gating by forming abnormally tight domain-domain interaction between the S2246L mutable domain and the K201-binding domain. This produces more global conformational change in the RyR2: namely, an aberrant domain unzipping between the N-terminal (a.a. 1–600) domain and the central (a.a. 2000–2500) domain owing to the allosteric conformational coupling mechanism. Pharmacological correction of the defective inter-domain interactions can stop the aberrant Ca^2+ release and lethal arrhythmia. These results provide a new pathogenic mechanism of CPVT and a novel therapeutic strategy against CPVT

中国では，2014年3月に中国教育部により，『全面的に課程改革を推進し，立徳樹人の根本的な任務を達成する意見』が公布され，核心素養（キー・コンピテンシー）という言葉が教育領域で注目されるようになった。これにより，中国の基礎教育（初等中等教育）方針が素質教育（資質教育）から核心素養の育成へと転換することになった。核心素養を基に，各教科の授業目標や計画，評価，カリキュラムの開発と実践において，授業現場の各段階に大きな変化があった。本研究は核心素養を背景にし，中国における美術教員の育成のため，小中学校の授業現場でどのようなカリキュラムの開発が適切か，どのように実践されるかについて陝西師範大学での事例を基に考察する。

Abstract Background: Expanding nursing workload is a worldwide problem. However, any nursing workload assessment (NWA) tool requires complicated analyses of the nursing job profile. To determine the imbalance in time assignments across all nursing operations and to reduce nursing workload, a nursing job survey was conducted. Methods: A total of 25 major job categories, common to all hospital wards, were identified, and an NWA tool was developed for efficient analyses to feature easy/flexible entry of the time spent for each job category and real-time visual profiling of job time allocation. The profile could be divided by job categories, wards, shifts, and years. Results: From the preliminary analyses, undesirable time allocation was revealed in several job categories, especially the time for recording and other nonessential nursing operations. Using the analytical functions of the NWA tool between 2014 and 2016, a series of corrective measures were successfully taken to many job categories, and they were found to be effective. Consequently, excessive overtime workload was reduced from 125 min/day/nurse in 2014 to 100 and 100 min/day/ nurse in 2015 and 2016, respectively. Conclusion: Notable improvements in nursing workload and time allocation for attentive patient care could be achieved employing the novel user-aimed NWA tool.