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Medical Science & Innovation Volume 71 Issue 3-4 pp. 45 - 49
published_at 2024-12
I, Professor Nobuaki Tanaka, gave a Farewell Lecture on February 29, 2024. First, I talked about the episode that led me to start researching aortic stenosis, and reflected on my own lectures on this topic to students aiming to become medical laboratory scientist. Lastly, I spoke to students majoring in medical laboratory scientist about the importance of practical clinical training.
Creators : Tanaka Nobuaki Publishers : Yamaguchi University School of Medicine Updated At : 2024-09-26 09:56:15
Medical Science & Innovation Volume 71 Issue 3-4 pp. 75 - 85
published_at 2024-12
Access to high-quality care at the end-of-life is a fundamental human right; therefore, it is necessary to examine how end-of-life care should be taught in nursing education to prepare for a super-aging society. Japan and Hong Kong are both in the East Asian region and are facing similar super-aging challenges, such as increased mortality and declining birth rates. This paper explores the literature on this topic and discusses how end-of-life care is taught in undergraduate nursing education in both Japan and Hong Kong. A comprehensive literature search was performed using end-of-life care keywords. Subsequently, the authors engaged in a discourse on expert perspectives, insights, and results from the literature. It is necessary to bridge the gap between the desired manner of spending oneʼs final days and the practical reality of considering patientsʼ best interests by referring to the existing policies, laws, guidelines, and frameworks of healthcare systems. This study suggests the importance of understanding patientsʼ views on life, death, values, and cultural backgrounds and educating healthcare personnel to apply these principles flexibly in their practice.
Creators : Tanaka Aiko | Murakami Kyoko | Ito Misae | Tai Chun John Fung | Siu Ling Chan | Claudia Lai Publishers : Yamaguchi University School of Medicine Updated At : 2024-11-20 14:25:42
Medical Science & Innovation Volume 71 Issue 1-2 pp. 21 - 33
published_at 2024-06
Vestibular hair cells are susceptible to damage from various stimuli such as infections, ischemia, and certain therapeutic drugs, including aminoglycoside antibiotics and the antineoplastic agent cisplatin. In mammals, damage to the vestibular hair cells is permanent. This study aimed to evaluate the protective effects of nobiletin (NOB) against aminoglycoside-induced hair cell death using utricles collected from adult mice. The utricles removed from CBA/N mice were assigned to eight groups according to the dose of NOB and the administration or not of neomycin. Hair cells in the utricles were counted by double labeling with calmodulin and calbindin. NOB inhibited hair cell death in utricles exposed to neomycin. The protective effect of NOB on hair cells in the utricles was also suggested to have resulted from the inhibition of the production and accumulation of 4-hydroxy-2-nonenal, the final product of lipid peroxide aldehyde. NOB suppressed neomycin-induced hair cell death. The principle of hair cell protection from aminoglycoside-induced hair cell death suggests that NOB inhibits reactive oxygen species formation in the utricles exposed to neomycin.
Creators : Masaki Tatsuya | Sugahara Kazuma | Hashimoto Makoto | Yamashita Hiroshi Publishers : Yamaguchi University School of Medicine Updated At : 2024-06-21 11:51:30
Medical Science & Innovation Volume 71 Issue 1-2 pp. 9 - 20
published_at 2024-06
Objective: The objective was to explore the potential existence and nature of the relationship between serum of uric acid (SUA) and serum uric acid to serum creatinine ratio (SUA/SCr) with reduced estimated glomerular filtration rate (eGFR) in patients with non-alcoholic fatty liver disease (NAFLD). Methods: A cross-sectional study was conducted among apparently healthy subjects with NAFLD (n=485). The association between tertiles of SUA and SUA/SCr with reduced eGFR (n=56) were investigated after adjustments for potentially relevant confounders. Also, the diagnostic performances of SUA and SUA/SCr were evaluated with the receiver operating characteristic (ROC) curve analysis. Results: In the adjusted models, SUA showed a significant positive association with reduced eGFR in the highest tertile (OR 5.65, 95% CI 2.48-12.86, p<0.001), and SUA/SCr, in the lowest tertile (4.21, 95% CI 1.76-10.07, p=0.001). The ROC curve analysis did not reveal any significant difference between the corresponding values of area under the curve for SUA and SUA/SCr (0.70 and 0.67, respectively; p=0.521). Conclusions: We revealed significant and independent associations of elevated SUA and reduced SUA/SCr with kidney function decline in NAFLD. However, the clinical utility of these two biomarkers seemed to be limited for the mentioned purpose and needs further investigations.
Creators : Shimokawa Junki | Mahbub MH | Yamaguchi Natsu | Hase Ryosuke | Wada Sunao | Saito Hiroyuki | Watanabe Rie | Matsumoto Shoko | Nakagami Yuki | Kurokawa Fumie | Tanabe Tsuyoshi Publishers : Yamaguchi University School of Medicine Updated At : 2024-06-21 11:36:34
Medical Science & Innovation Volume 71 Issue 1-2 pp. 1 - 8
published_at 2024-06
Benign paroxysmal positional vertigo (BPPV) is the most common vertigo disease and is more likely to occur in perimenopausal women, suggesting an association with osteoporosis. Since otoconia are primarily composed of calcium carbonate, abnormal calcium metabolism may lead to otoconia dislocation. However, the detailed mechanism is currently unknown. In this study, we investigated the effects of drugs (cadmium and dexamethasone) that cause abnormal calcium metabolism on otolith formation in zebrafish larvae. Here, otolith size was clearly reduced in the cadmium group, and the calcium content of the larvae was also markedly reduced. In contrast, in the dexamethasone group, which also had a lower calcium content than the control group, otolith size increased. Our results suggest that, as in bone, calcium metabolism influences the repeated dissolution and recrystallization of otoliths and maintains homeostasis in response to calcium concentrations in the endolymphatic fluid.
Creators : Iwamoto Aya | Sugahara Kazuma | Hashimoto Makoto | Yamashita Hiroshi Publishers : Yamaguchi University School of Medicine Updated At : 2024-06-21 11:27:58
Medical Science & Innovation Volume 70 Issue 3-4 pp. 19 - 26
published_at 2023-12
Right ventricular (RV) dysfunction and its linked arrhythmias play a crucial role in determining the prognosis of pulmonary arterial hypertension (PAH). Our paper aimed to explore the potential protective effects of direct pharmacological intervention in the RV muscle using dantrolene (DAN), a stabilizer of the cardiac ryanodine receptor (RyR2), against RV dysfunction and arrhythmia in a rat model of monocrotaline (MCT)-induced PAH. To induce PAH, male 8-week-old Sprague-Dawley rats received MCT injections. The study also assessed the induction of ventricular tachycardia (VT) by catecholamines, examining RyR2-mediated Ca^{2+} release properties in isolated cardiomyocytes. Additionally, a pulmonary artery-banding model was established to evaluate the independent effects of chronic pressure overload on RV morphology and function. In the MCT-induced PAH rat model, findings revealed RV hypertrophy, dilation, and functional decline, resulting in 0% survival rate two months post-MCT induction. Conversely, chronic DAN treatment demonstrated improvements in these RV parameters and an 80% increase in survival. Furthermore, chronic DAN treatment prevented the dissociation of calmodulin from RyR2, inhibiting Ca^{2+} sparks and spontaneous Ca^{2+} transients in MCT-induced hypertrophied RV cardiomyocytes. Epinephrine induced VT in over 50% of rats with MCT-induced PAH, while chronic DAN treatment achieved complete suppression of VT. The paper concludes that stabilizing RyR2 with DAN holds promise as a novel therapeutic approach against the development of RV dysfunction and fatal arrhythmias associated with PAH.
Creators : Tanaka Shinji | Yamamoto Takeshi | Kobayashi Shigeki | Yano Masafumi Publishers : Yamaguchi University School of Medicine Updated At : 2024-02-06 15:11:02
Medical Science & Innovation Volume 70 Issue 1-2 pp. 7 - 17
published_at 2023-06
To investigate whether dantrolene (DAN), cardiac ryanodine receptor (RyR2) stabilizer, improves impaired diastolic function in an early pressure-overloaded hypertrophied heart, pressure-overload hypertrophy was induced by transverse aortic constriction (TAC) in mice. Wild-type (WT) mice were divided into four groups: sham-operated mice (Sham), sham-operated mice treated with DAN (DAN+Sham), TAC mice (TAC), and TAC mice treated with DAN (DAN+TAC). The mice were then followed up for 2 weeks. Left ventricular (LV) hypertrophy was induced in TAC, but not DAN+TAC mice, 2 weeks after TAC. There were no differences in LV fractional shortening among the four groups. Catheter tip micromanometer showed that the time constant of LV pressure decay, an index of diastolic function, was significantly prolonged in TAC but not in DAN+TAC mice. Diastolic function was significantly impaired in TAC, but not in DAN+TAC mice as determined by cell shortening and Ca^{2+} transients. An increase in diastolic Ca^{2+} leakage and a decrease in calmodulin (CaM) binding affinity to RyR2 were observed in TAC mice, while diastolic Ca^{2+} leakage improved in DAN+TAC mice. Thus, DAN prevented the progression of hypertrophy and improved the impairment of LV relaxation by inhibiting diastolic Ca^{2+} leakage through RyR2 and the dissociation of CaM from RyR2.
Creators : Chang Yaowei | Kobayashi Shigeki | Yano Yasutake | Uchida Tomoyuki | Nawata Junya | Fujii Shohei | Nakamura Yoshihide | Suetomi Takeshi | Uchinoumi Hitoshi | Oda Tetsuro | Yamamoto Takeshi | Yano Masafumi Publishers : Yamaguchi University School of Medicine Updated At : 2023-05-19 14:46:45
Medical Science & Innovation Volume 70 Issue 1-2 pp. 1 - 6
published_at 2023-06
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by a single point mutation in the cardiac type 2 ryanodine receptor (RyR2). Using knock-in mouse (KI) model (R2474S/+), we previously reported that a single point mutation within the RyR2 sensitized the channel to agonists, primarily mediated by defective inter-domain interaction within the RyR2 and subsequent dissociation of calmodulin (CaM) from the RyR2. Here, we examined whether CPVT can be genetically rescued by enhancing the binding affinity of CaM to the RyR2. We first determined whether there was a possible amino-acid substitution within the CaM-binding domain in the RyR2 (3584-3603) that can enhance its binding affinity to CaM, and found that V3599K substitution showed the highest binding affinity of CaM to CaM-binding domain. Hence, we generated a heterozygous KI mouse model (V3599K/+) with a single amino acid substitution in the CaM-binding domain of the RyR2, and crossbred it with the heterozygous CPVT –associated R2474S/+ KI mouse to obtain a double heterozygous R2474S/V3599K KI mouse model. The CPVT phenotypes, bidirectional or polymorphic ventricular tachycardia, were inhibited in the R2474S/V3599K mice. Thus, enhancement of the CaM binding affinity of the RyR2 is essential to prevent CPVT-associated arrhythmogenesis.
Creators : Nakamura Yoshihide | Yamamoto Takeshi | Kobayashi Shigeki | Yano Masafumi Publishers : Yamaguchi University School of Medicine Updated At : 2023-05-19 14:21:41
Creators : 森永 明日香 Updated At : 2024-06-05 13:15:27
Creators : Han Jihae Updated At : 2021-06-11 20:38:01
Chromatography is considered as a key operation in the downstream process (DSP) of biopharmaceuticals, including proteins. Therapeutic proteins such as monoclonal antibodies (mAbs) with high economic values in the global market require immediate innovation in the purification step to adapt to the increased throughput from upstream. Authorities have also initiated changes toward a more modernized pharmaceutical manufacturing platform which is agile and flexible without extensive oversight. Instead of the conventional batch operation and empirical models, the design and application of in silico modeling and simulation for integrated multi-column processes to improve their performance in capture chromatography steps have been explored in the dissertation. Due to the fact that mechanistic models can reveal adsorption and mass transfer behaviors better in the chromatography compared to statistical models, mechanistic frameworks were applied in the study. Ion-exchange and protein A chromatography, the main categories of therapeutic protein chromatography were examined. With an example of oligonucleotides, the mass transfer phenomenon of biomolecules in different types of ion-exchange resins was explored by mechanistic models. The results demonstrate the effectiveness of modeling approaches to understand the chromatography process of biopharmaceuticals. By focusing on the DSP of mAbs, multi-column continuous chromatography was examined with IgG samples. The study covered the repeating batch to 4-column settings in the continuous periodic counter-current (PCC) chromatography, with development in modeling and simulation tools for process quantification and evaluation. Process performances including productivity, capacity utilization, and buffer consumption were investigated by simulations with the aim to increase productivities and lower buffer consumptions, which are the main bottleneck in the current DSP. The critical operation parameter, breakthrough percent (BT%) for column switching in PCC processes, requires the information from binding capacity, mass transfer, and non-loading operations. To obtain the optimal BT% under synchronized conditions, numerical solvers developed from mechanistic models were employed. It was found that over 20% improvement in buffer consumption and resin utilization can be observed in PCC processes while the same productivity as batch operation is maintained. Furthermore, regressive relations were developed for predictions of process performances and BT% based on the findings from PCC simulations. With high coherence in R2 over 0.95, the linear regression function can act as an accelerated method in the PCC process design. Finally, a new strategy of linear flow-velocity gradient (LFG) in the loading step was explored as a supplement to increase process efficiency. The method controls the total column capacity and the loaded amount as functions of time. Based on the relationship between the dynamic binding capacity and residence time, the gradient time of LFG was obtained. The optimal flow velocities and time gradients were examined by scanning through the range of applicable residence times. A case study of the 4-column PCC process is presented. By integrating a linear decreasing flow gradient in the PCC loading operation, the productivity has 1.4 times enhancement along with a 13% reduction in the cost of resin per amount of processed mAbs compared to constant flows. Undoubtedly, the next generation of DSP platform technology is directed toward continuous and integrated systems. Regarding the advantages in process performances and regulation perspectives, continuous manufacturing can advance development and manufacturing while assuring the product quality. The evolution in modeling and simulation enables faster development of in silico process prediction and evaluation. With the support from models, process design and optimization in chromatography can rise to the challenge.
Creators : Chen Chyi Shin Updated At : 2021-06-11 20:38:01
Creators : 後藤 奈穂 Updated At : 2023-12-12 16:38:51
山口大学教育学部学部・附属教育実践研究紀要 Volume 12 pp. 87 - 99
published_at 2013-03-25
Creators : Kawasaki Tokuko | Shiraishi Toshiyuki | Ohmori Yoko | Takata Kazuyoshi | Shiga Naomi | Tujimura Asuka | Takemiya Michiko | Nakamura Makiko | Ooba Miyuki | Nakashima Hisako Publishers : 山口大学教育学部 Updated At : 2014-12-08 19:37:09
山口大学教育学部学部・附属教育実践研究紀要 Volume 11 pp. 1 - 12
published_at 2012-03-25
Creators : Kawasaki Tokuko | Takata Kazuyoshi | Ohmori Yoko | Shiga Naomi | Takemiya Michiko | Tujimura Asuka | Nakamura Makiko | Ohba Miyuki | Nakashima Hisako | Shiraishi Toshiyuki Publishers : 山口大学教育学部 Updated At : 2014-12-05 23:17:14
山口大学教育学部学部・附属教育実践研究紀要 Volume 13 pp. 135 - 142
published_at 2014-03-25
Creators : Takata Kazuyoshi | Takemiya Michiko | Tujimura Asuka | Nakamura Makiko | Ohmori Yoko | Shiga Naomi | Ooba Miyuki | Nakashima Hisako | Kawasaki Tokuko | Shiraishi Toshiyuki Publishers : 山口大学教育学部 Updated At : 2015-01-22 19:36:40
山口大学教育学部学部・附属教育実践研究紀要 Volume 14 pp. 45 - 56
published_at 2015-03-20
Creators : Nakashima Hisako | Kawasaki Tokuko | Shiraishi Toshiyuki | Murakami Kiyofumi | Nakamura Makiko | Ohmori Yoko | Takata Kazuyoshi | Shiga Naomi | Takemiya Michiko | Tsujimura Asuka | Ooba Miyuki | Nakano Tomoko | Tsurunaga RIe | Nakao Tomomi Publishers : 山口大学教育学部 Updated At : 2015-06-24 22:19:55
Yamaguchi journal of economics, business administrations & laws Volume 73 Issue 1-2 pp. 73 - 88
published_at 2024-07-31
Creators : Yanagisawa Noboru Publishers : The Economic Society of Yamaguchi University Updated At : 2024-12-02 16:34:47
Yamaguchi journal of economics, business administrations & laws Volume 73 Issue 1-2 pp. 55 - 71
published_at 2024-07-31
Creators : Kato Shinya | Kojima Hisashi Publishers : The Economic Society of Yamaguchi University Updated At : 2024-12-02 16:23:28
Yamaguchi journal of economics, business administrations & laws Volume 73 Issue 1-2 pp. 25 - 54
published_at 2024-07-31
Creators : Kato Shinya | Kojima Hisashi Publishers : The Economic Society of Yamaguchi University Updated At : 2024-12-02 15:37:17
Yamaguchi journal of economics, business administrations & laws Volume 73 Issue 1-2 pp. 1 - 23
published_at 2024-07-31
Creators : Kinoshita Makoto | Shiroshita Kengo Publishers : The Economic Society of Yamaguchi University Updated At : 2024-12-02 15:22:51
Asian economic review Volume 82 Issue 1-2 pp. 117 - 129
published_at 2024-01-31
Creators : Yang Qin | Sun Yunyi | Li Haifeng | Li Qinlin | Yu Mengning Publishers : The TOA-KEIZAI Gakkai, Yamaguchi University Updated At : 2024-10-22 14:35:11