Study on the Teaching Strategy of an Junior High School and Improving the Program for Training Students to be teachers of University (1) : In the Case of Japanese Language, Arithmetic, Science and Social Studies

　本研究は，教科内容構成の考え方に基づいて中学校の授業づくりのあり方を検討するとともに，それをふまえることで大学の教員養成プログラムの授業が具体的にどのように改善されるかを明らかにしようとしたものである。教科内容構成とは，教員養成において従来から課題とされてきた教科の内容に関わる知識・技能と教科の指導法に関わる知識・技能の分離という問題を克服するために提案されたものである。教科内容構成は，教科の内容と指導法に関わる知識・技能を統合し，それらを応用して，教師が自ら「どのような内容をどのように教えるべきか」を考え，授業づくりに取り組むことができるようになるための考え方を示すものであり，本研究では教員養成プログラムにおける具体的な授業プランを提示してそれを明らかにしていく。本稿では，特に，中学校の国語科，数学科，理科，社会科を事例として論じていくことにしたい

去勢抵抗性前立腺癌におけるKlothoγのドセタキセル抵抗性との関連と新規治療としての可能性

The Klotho (KL) gene was first identified as a potent aging suppressor. The KL family currently comprises of three proteins: α-Klotho (KLA), β-Klotho (KLB), and γ-Klotho (KLG). Many studies have shown that KLA and KLB participate in tumor progression or suppression, depending on the type of cancer; however, the relationship between KLG and prostate cancer has not yet been studied. Some studies have claimed that KL is correlated to sensitivity to chemotherapy. Here, we investigated the oncogenic potential of KLG in castration-resistant prostate cancer (CRPC). Immunohistochemical analysis using prostate biopsy specimens revealed that patients with high KLG expression in primary prostate cancer tissue had a significantly poor prognosis for overall survival. In addition, the prostate-specific antigen response rate after docetaxel (DTX) therapy in patients with high KLG expression was lower than that in patients with low KLG expression. To evaluate the potential of KLG as a therapeutic target in human prostate cancer, we generated a xenograft model of human CRPC cell line (PC-3) in male athymic mice. The animals were randomly divided into four groups as follows: i) control group (vehicle only); ii) DTX group (intraperitoneal administration); iii) small interfering RNA targeting KLG (KLG siRNA) group (intratumoral administration); and iv) a combination group (DTX plus KLG siRNA). After 3 weeks of treatment, the tumor weight and tumor Ki-67 labeling index were significantly lower in the KLG siRNA group and the combination group than in the control group. Sensitivity to DTX was increased upon treatment with KLG siRNA. These findings suggest that KLG expression in primary prostate cancer lesions is associated with resistance to DTX in CRPC and has potential as a diagnostic and therapeutic target for patients with CRPC.博士（医学）・甲第740号・令和2年3月16日Copyright: © Onishiet al. This is an open access article distributed under theterms of CreativeCommons Attribution License(https://creativecommons.org/licenses/by-nc-nd/4.0/)

The Impact of Reduced Skeletal Muscle Mass on Patients with Knee Osteoarthritis

Although several studies have suggested a possible association between sarcopenia and knee osteoarthritis (OA) in the elderly, there remains no definitive evidence. Recently, however, the serum creatinine/cystatin C ratio (sarcopenia index: SI) was reported to correlate with skeletal muscle mass. The present retrospective study therefore investigated the impact of reduced skeletal muscle mass on advanced knee OA using SI. In 55 individuals scheduled for knee osteotomy or knee arthroplasty, correlations between SI and patient-reported outcomes such as the Knee Society Score (KSS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Oxford Knee Score (OKS) were explored. Significant associations were found between SI and the KSS functional activity score (β=0.37; p=0.022), KOOS subscale for activities of daily living (β=0.42; p=0.0096), and OKS (β=0.42; p=0.0095). This study underscores the role of reduced muscle mass in functional outcomes and introduces SI as a valuable marker for assessing muscle loss in knee OA patients

限局性腎細胞癌における腫瘍浸潤性リンパ球と関連サイトカインの予後因子としての意義

Renal cell carcinoma (RCC) is an immunogenic tumor and pathological specimen generally contain large quantities of tumor-infiltrating lymphocytes (TILs). Numerous cell types and cytokines could affect the immune escape mechanism of tumor cells. The aim of the present study was to investigate the prognostic impact of TILs and the associated circulating cytokines on localized clear cell RCC following radical nephrectomy. A total of 87 patients who had undergone radical nephrectomy and were pathologically diagnosed with localized clear cell RCC were included. The present study evaluated the profile of TILs with immunohistochemical analysis of tumor specimens using a panel of antibodies [cluster of differentiation (CD)-4, CD8, CD80, CD86, CD276, and Forkhead box p3 (Foxp3)]. Counts of each TIL were compared with clinicopathological variables. Based on the results of immunohistochemical analyses, putative cytokines, including interleukin (IL)-6, IL-10, IL-17, interferon-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β, were selected, and their levels in preoperative serum were measured by ELISA. The levels were compared with TIL counts in tumor specimens. High counts of the CD276+ and Foxp3+ TILs were identified as independent factors for poor prognosis for metastasis and local recurrence following radical nephrectomy (P=0.033 and 0.006, respectively). A high CD276+ TIL count was associated with preoperative serum levels of TNF-α and IFN-γ (P=0.027 and P=0.035, respectively), whereas a high count of Foxp3+ TILs was associated with preoperative serum levels of TGF-β (P=0.021). High levels of TNF-α and TGF-β were associated with recurrence-free survival (P=0.035 and P=0.031, respectively). Topical intra-tumoral immunoreaction and systemic immune status may be associated with patients with localized RCC. The topical induction of the CD276+ and Foxp3+ TILs was suggested to be associated with high levels of serum TNF-α and IFN-γ. Preoperative serum levels of TNF-α and TGF-β could be simple and non-invasive biomarkers for risk stratification before radical surgery.博士（医学）・甲第741号・令和2年3月16日Copyright © Spandidos Publications 2019. All rights reserved.Articles from Oncology Letters are provided here courtesy of Spandidos Publications

Study on the Teaching Strategy of an Elementary School and Improving the Program for Training Students to be Teachers of University (2) :In the Case of Social Studies, Music, Physical Education and Information Ethics Education

　本研究は，教科内容構成の考え方に基づいて小学校の授業づくりのあり方を検討するとともに，それをふまえることで大学の教員養成プログラムの授業が具体的にどのように改善されるかを明らかにしようとしたものである。教科内容構成とは，教員養成において従来から課題とされてきた教科の内容に関わる知識・技能と教科の指導法に関わる知識・技能の分離という問題を克服するために提案されたものである。教科内容構成は，教科の内容と指導法に関わる知識・技能を統合し，それらを応用して，教師が自ら「どのような内容をどのように教えるべきか」を考え，授業づくりに取り組むことができるようになるための考え方を示すものであり，本研究では教員養成プログラムにおける具体的な授業プランを提示してそれを明らかにしていく。本稿では，特に，小学校の社会科，音楽科，体育科，情報モラル教育を事例として論じていくことにしたい

Relation of leg phase angle from bioelectrical impedance analysis with voluntary and evoked contractile properties of the plantar flexors

Introduction: Bioelectrical impedance analysis (BIA) can noninvasively and quickly assess electrical properties of the body, such as the phase angle. Phase angle is regarded as the quantity and/or quality of skeletal muscle and is associated with exercise performance, such as jump height and walking speed. Although the phase angle derived from BIA is assumed to be a useful way to assess muscle function, the relationship between the phase angle and neuromuscular properties has not been fully investigated. The purpose of this study was to investigate the association of phase angle with voluntary and evoked contractile properties in 60 adults (age, 21–83 years; 30 females and 30 males).Methods: The phase angle of the right leg at 50 kHz was evaluated using BIA. The twitch contractile properties (peak twitch torque [PTtwitch], rate of twitch torque development [RTDtwitch], and time-to-PTtwitch [TPTtwitch]) of the plantar flexors were measured using tibial nerve electrical stimulation. Maximal voluntary isometric contractions (MVICs) were performed to measure the maximal muscle strength and explosive muscle strength, from which the peak MVIC torque (PTMVIC) and rate of torque development (RTD) over a time interval of 0–200 ms were assessed, respectively. The root mean square (RMS) values of electromyographic (EMG) activity during the PTMVIC and RTD measurements (EMG-RMSMVIC and EMG-RMSRTD, respectively) were calculated. The RTD and EMG-RMSRTD were normalized using PTMVIC and EMG-RMSMVIC, respectively.Results and discussion: Phase angle significantly correlated with twitch contractile properties (|r| ≥ 0.444, p < 0.001), PTMVIC (r = 0.532, p < 0.001), and RTD (r = 0.514, p < 0.001), but not with normalized RTD (r = 0.242, p = 0.065) or normalized EMG-RMSRTD (r = −0.055, p = 0.676). When comparing measurement variables between the low- and high-phase angle groups while controlling for sex and age effects, the high-phase angle group showed greater PTtwitch, RTDtwitch, PTMVIC, and RTD (p < 0.001) and shorter TPTtwitch (p < 0.001) but not normalized RTD (p = 0.184) or normalized EMG-RMSRTD (p = 0.317). These results suggest that the leg phase angle can be an indicator of voluntary and evoked muscle contractile properties but not the neuromuscular activity of the plantar flexors, irrespective of sex and age

AGEs activate mesangial TGF-β–Smad signaling via an angiotensin II type I receptor interaction

AGEs activate mesangial TGF-β–Smad signaling via an angiotensin II type I receptor interaction.BackgroundThe renin-angiotensin system (RAS) and the accumulation of advanced glycation end products (AGEs) have been implicated in the pathogenesis of diabetic nephropathy. Whether there is a functional interaction between the RAS and AGEs in diabetic nephropathy is not known. In this study, we investigated whether AGEs could activate autocrine angiotensin II (Ang II) signaling and subsequently induce transforming growth factor-β (TGF-β)–Smad signaling in cultured rat mesangial cells.MethodsThe intracellular formation of reactive oxygen species (ROS) was detected using the fluorescent probe CM-H2DCFDA. Ang II was measured by radioimmunoassay. TGF-β released into media was quantitatively analyzed in an enzyme-linked immunosorbent assay (ELISA). Smad2, p27Kip1 (p27), fibronectin, and receptor for AGEs (RAGE) protein expression were determined by Western blot analysis. TGF-β–inducible promoter activity was analyzed by a luciferase assay. DNA synthesis was evaluated by 5-bomo-2′-deoxyuridine (BrdU) incorporation and de novo protein synthesis was determined by [3H]leucine incorporation.ResultsAGEs increased intracellular ROS generation in mesangial cells, and this effect was significantly inhibited by an antiserum against RAGE. AGEs also were found to stimulate Ang II production in a time- and dose-dependent manner, which was completely prevented by an antioxidant, N-acetylcysteine (NAC). AGE-induced TGF-β overproduction was completely blocked by candesartan, an Ang II type 1 receptor (AT1R) antagonist. Both candesartan and neutralizing antibody against TGF-β completely prevented AGEs-induced Smad2 phosphorylation and TGF-β–inducible promoter activity. Furthermore, AGEs were found to inhibit DNA synthesis and to stimulate de novo protein synthesis and fibronectin production in association with up-regulation of p27. All of these phenomena were completely prevented by candesartan or a polyclonal antibody against TGF-β.ConclusionThe present study suggests that AGE-RAGE–mediated ROS generation activates TGF-β–Smad signaling and subsequently induces mesangial cell hypertrophy and fibronectin synthesis by autocrine production of Ang II. This pathway may provide an important link between metabolic and haemodynamic factors in promoting the development and progression of diabetic nephropathy

近赤外線スペクトロスコピィを用いた覚醒剤精神病と統合失調症の鑑別

Despite some slight differences in symptomatology, differential diagnosis of methamphetamine-induced psychosis (MAP) versus schizophrenia can be challenging because both disorders present a large overlap in their clinical symptoms. However, a recent study has shown that near-infrared spectroscopy (NIRS) performed during a cognitive task can be a powerful tool to differentiate between these two disorders. Here, we evaluated verbal fluency task performance during NIRS in 15 patients diagnosed with MAP and 19 with schizophrenia matched for age and sex. We used prefrontal probes and a 24-channel NIRS machine to measure the relative concentrations of oxyhaemoglobin every 0.1 s during the task. For each patient, the neurocognitive function and clinical psychopathology were evaluated using the Positive and Negative Symptom Scale (PANSS), and the Brief Assessment of Cognition in Schizophrenia (BACS). Oxyhaemoglobin changes in the prefrontal cortex were significantly higher in the MAP group compared to those in the schizophrenia group, particularly in the right dorsolateral prefrontal cortex. In contrast, we found no significant difference in PANSS and BACS scores. Our findings suggest that NIRS measurement could be applied to differentiate patients with MAP from those with schizophrenia, even in cases where clinical symptoms are similar.博士（医学）・甲第645号・平成28年3月15日This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0

尿路上皮癌微小環境内におけるDisabled Homolog 2 (DAB2) は腫瘍細胞上皮間葉転換を介して遊走能・浸潤能を高める

Disabled homolog-2 (DAB2) has been reported to be a tumor suppressor gene. However, a number of contrary studies suggested that DAB2 promotes tumor invasion in urothelial carcinoma of the bladder (UCB). Here, we investigated the clinical role and biological function of DAB2 in human UCB. Immunohistochemical staining analysis for DAB2 was carried out on UCB tissue specimens. DAB2 expression levels were compared with clinicopathological factors. DAB2 was knocked-down by small interfering RNA (siRNA) transfection, and then its effects on cell proliferation, invasion, and migration, and changes to epithelial-mesenchymal transition (EMT)-related proteins were evaluated. In our in vivo assays, tumor-bearing athymic nude mice subcutaneously inoculated with human UCB cells (MGH-U-3 or UM-UC-3) were treated by DAB2-targeting siRNA. Higher expression of DAB2 was associated with higher clinical T category, high tumor grade, and poor oncological outcome. The knock-down of DAB2 decreased both invasion and migration ability and expression of EMT-related proteins. Significant inhibitory effects on tumor growth and invasion were observed in xenograft tumors of UM-UC-3 treated by DAB2-targeting siRNA. Our findings suggested that DAB2 expression was associated with poor prognosis through increased oncogenic properties including tumor proliferation, migration, invasion, and enhancement of EMT in human UCB.博士（医学）・甲第768号・令和3年3月15日© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)