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 香川共同リポジトリは、香川県内で生産された学術研究成果を電子的に収集、整 理、保存し、インターネットを通じて無償で提供することを目的として公開して います。

*平成23年度国立情報学研究所最先端学術情報基盤(CSI)構築推進委託事業です。

kuir is 6648
total is 7219
Twin fetal facial expressions at 30-33+6 weeks of gestation 新田 絵美子 Nitta Emiko
Abstract Objective To assess the characteristics of twin fetal facial expressions at 30-33 + 6 weeks of gestation using four-dimensional (4D) ultrasound to clarify twin fetal brain development and maturation. Methods Frequencies of seven fetal facial expressions were studied using 4D ultrasound for 15 minutes in 30 singleton pregnancies and 18 twin pregnancies [four monochorionic diamniotic (MD) and 14 dichorionic diamniotic (DD) twins] at 30-33 + 6 weeks of gestation. Comparison of the frequency in each facial expression was performed between singleton and twin fetuses. Results Mouthing was the most frequent facial expression at 30-33 + 6 weeks of gestation, followed by blinking in twin and singleton fetuses. Both facial expressions were significantly more frequent than other expressions (P < 0.05). The frequencies of mouthing and scowling in twin fetuses were significantly lower than those in singleton fetuses, but there were no significant differences in the frequencies of the five other facial expressions between the fetal groups. Conclusion Our results suggest that restricted twin fetal behavior before 20 weeks of gestation may still affect the frequencies of twin facial expressions early in the third trimester of pregnancy. Moreover, the frequencies of facial expressions in twins are different from those of singleton fetuses. Keywords: 4D ultrasound; facial expression; singleton fetus; third trimester of pregnancy; twin fetus. (医博乙291)

HDlive Flow Silhouette Mode for Assessment of Tumor Vascularity in Advanced Cervical Cancer. 田中 圭紀 Tanaka Tamaki
Abstract Objective: To present our experience in assessing tumor vascularity in advanced cervical cancer using the HDlive flow silhouette mode. Materials and methods: Thirteen advanced cervical cancer patients (11 squamous cell carcinoma (SCC) patients and 2 gastric-type mucinous carcinoma (GAS) patients) were studied using the HDlive flow silhouette mode. Tumor vascularity was assessed using the subjective grading system (grade I, minimal blood flow pattern; grade II, moderate blood flow pattern; and grade III, abundant blood flow pattern). Results: The number of patients with grade I was 0, that of grade II was 4 (36.4%), and that of grade III was 7 (63.6%) in the SCC group, whereas that of grade I was 2 (100%) in the GAS group (p = 0.0128). Conclusion: Tumor vascularity may differ between SCC and GAS advanced cervical cancers. A grading system using the HDlive flow silhouette mode may provide useful, additional information on the assessment of tumor vascularity in the treatment effect on advanced cervical cancers. Further studies involving a larger sample size are needed to confirm the validity of this grading system using the HDlive flow silhouette mode for the assessment of tumor vascularity in advanced cervical cancer patients. Keywords: Advanced cervical cancer, Gastric-type mucinous carcinoma, HDlive flow silhouette mode, Squamous cell carcinoma, Tumor vascularity. Donald School Journal of Ultrasound in Obstetrics and Gynecology (2019): 10.5005/jp-journals-10009-1597 (医博乙290)

Comprehensive analysis of circulating microRNAs as predictive biomarkers for sorafenib therapy outcome in hepatocellular carcinoma 河野 知樹 Kohno Tomoki
Abstract Hepatocellular carcinoma (HCC) is the third leading cause of cancer‑related death worldwide. Clinical management has improved the prognosis of early HCC, but that of advanced HCC remains poor. Sorafenib, an oral multikinase inhibitor, provided a treatment option for advanced‑stage HCC, and prolonged the survival and inhibited tumor progression as first‑line therapy in patients with advanced HCC. In this study, we investigated if specific microRNAs could act as predictive biomarkers of sorafenib effectiveness and indicate the best time to switch to second‑line therapies. Sorafenib inhibited the proliferation of the Li‑7, Hep3B, HepG2 and Huh7 liver cancer cell lines (effective group), but not that of the HLE, HLF and ALEX cancer cell lines (non‑effective group). A microRNA (miRNA/miR) analysis was performed comparing sorafenib‑effective and non‑effective cells lines as well as serum samples from patients with HCC from sorafenib‑effective (complete response/partial response) and ‑non‑effective (progressive disease) groups before sorafenib administration and detected three differentially‑expressed miRNAs that were common among the in vivo and in vitro samples. The increase rate (effective/non‑effective) of hsa‑miR‑30d in the medium was higher than that in the cancer cells. hsa‑miR‑30d was highly expressed in the serum and exosomes of patients with HCC in the effective group when compared to those of the non‑effective group. Additionally, the hsa‑miR‑30d expression in the medium of cancer cell lines was highly upregulated in the effective group compared with the non‑effective group. These results suggested that hsa‑miR‑30d might be secreted by the cancer cells to the serum through the exosomes. We identified a specific circulating miRNA that is related to refractory HCC under sorafenib therapy. Therefore, hsa‑miR‑30d might serve as a predictive biomarker for the efficacy of sorafenib therapy in HCC. (医博甲755)

Comparison of the prebiotic properties of native chicory and synthetic inulins using swine fecal cultures 中山 保典 Nakayama Yasunori
Abstract Inulin-type fructans are known to exert different effects on the fermentation profile depending on the average and range of the degree of polymerization (DP). Here, swine fecal cultures were used to investigate the prebiotic properties of native chicory inulin (NIN), extracted from the chicory root, and synthetic inulin (SIN), which has a narrower DP distribution than NIN. Both NIN and SIN showed prebiotic effects, but NIN exhibited a significant decrease in pH and increase in the production of propionate and butyrate compared to SIN. There were also differences in the production of succinate and lactate, the precursors of propionate and butyrate, and the relative abundance of associated genes. Furthermore, NIN induced the growth of certain species of Bifidobacterium and Lactobacillus more strongly than SIN. These results suggest that NIN and SIN exhibit different prebiotic properties due to differences in DP, and that NIN might be more beneficial to host health. Keywords: Inulin; fermentation; gut microbiota; prebiotics; short-chain fatty acids (医博甲754)

Bone metabolism of the jaw in response to bisphosphonate: A quantitative analysis of bone scintigraphy images 中井 史 Nakai Fumi
Abstract We examined the changes in the bone metabolism of the jaw in response to BP treatment, and we used bone SPECT-CT to analyze the site-specific bone metabolism between the jaw and other sites of bone. We compared the changes in the bone metabolism of each part of bone in response to BP treatment by performing a quantitative analysis of bone scintigraphy images between patients treated with low-dose BP for osteoporosis (LBP group; n = 17), those treated with high-dose BP for metastatic bone tumor (HBP group; n = 11), and patients with other oral disease who required bone scintigraphy, with no history of BP treatment (control group; n = 40). The study endpoint was the mean standardized uptake value (SUV) of the uptake of Tc-99 m methylene diphosphonate (MDP) in each group. The mean SUVs of the HBP group were significantly lower at the axial bone of the cervical vertebra, thoracic vertebra, sternum, and rib compared to those of the LBP and control groups. The LBP group's mean SUV was significantly higher at the temporal bone, the anodontia part of the alveolar bone in maxilla, the vital teeth part of alveolar bone in the mandible, and the temporomandibular joint. There was no significant difference among the three groups at the mandibular angle and mandibular ramus. Our analyses revealed that the bone metabolism of the jaw and temporal bone in the BP-treated patients was enhanced, and no suppression of bone remodeling in the jaw by BP was observed. Keywords: Bisphosphonate; Bone metabolism; Bone scintigraphy; Jaw; SUV (医博甲753)

Inhibition of cell-surface molecular GPR87 with GPR87-suppressing adenoviral vector disturb tumor proliferation in lung cancer cells 喜田 裕介 Kita Yusuke
Abstract Background/aim: GPR87 is a member of the cell surface molecular G protein-coupled receptors (GPCR) family and suggested to contribute to the viability of human tumor cells. Its tumor-specific expression and cell surface location make it a potential molecule for targeted therapy. In the present study, we aimed to examine the effect of silencing GPR87 expression and explore the possibility of establishing gene therapy against GPR87-overexpressing lung cancer. Materials and methods: Twenty malignant cell lines were investigated and GPR87-overexpressing H358 and PC9 lung cancer cells were subjected to inhibiting experiments. A short hairpin siRNA targeting the GPR87 gene was transformed into an adenoviral vector (Ad-shGPR87). Real-time RT-PCR and western blot analyses were performed to evaluate gene and protein expression. Tumors derived from human H358 cells were subcutaneously implanted in nude mice for in vivo experiments. Results and conclusion: About 50% (10/20) malignant cells showed GPR87-overexpression, especially for lung cancer cells (70%, 7/10). Ad-shGPR87 effectively down-regulated the GPR87 expression, and significantly inhibited the cell proliferation in GPR87-overexpressing H358 and PC9 cells. Treatment with Ad-shGPR87 exerted a significant antitumor effect against the GPR87-expressing H358 xenografts. In addition, the gene expression of H3.3, a recently proved activator for GPR87 transcription, was positively correlated with GPR87 gene expression. Furthermore, a significant decrease of KRAS and c-Myc expression was observed in both cell lines after Ad-shGPR87 infection. In conclusion, GPR87 may play a critical role in cancer cell proliferation, and indicate its potential as a novel target for lung cancer treatment. Keywords: GPR87; NSCLC; adenoviral vector; cell surface marker; gene therapy; shRNA (医博甲752)

Failure to confirm a sodium-glucose cotransporter 2 inhibitor-induced hematopoietic effect in non-diabetic rats with renal anemia 山﨑 大輔 yamazaki Daisuke
Abstract Aims/introduction: Clinical studies have shown that treatment with inhibitors of sodium-glucose cotransporter 2 (SGLT2) significantly increases the hematocrit in patients with type 2 diabetes. To investigate whether SGLT2 inhibitors directly promote erythropoietin production independently on blood glucose reduction, the hematopoietic effect of the specific SGLT2 inhibitor, luseogliflozin, was examined in non-diabetic rats with renal anemia. Materials and methods: Renal anemia was induced by treatment with adenine (200 or 600 mg/kg/day, orally for 10 days) in non-diabetic Wistar-Kyoto or Wistar rats, respectively. Luseogliflozin (10 mg/kg bodyweight) or vehicle (0.5% carboxymethyl cellulose) was then administered for 6 weeks. The hematocrit and the hemoglobin (Hb), blood urea nitrogen, plasma creatinine, and plasma erythropoietin levels were monitored. Results: Treatment with adenine decreased the hematocrit and the Hb level, which were associated with increases in the blood urea nitrogen and plasma creatinine levels. In Wistar-Kyoto rats treated with 200 mg/kg/day adenine, administration of luseogliflozin induced glycosuria, but did not change the blood urea nitrogen, plasma creatinine levels, hematocrit, Hb or plasma erythropoietin levels. Similarly, luseogliflozin treatment failed to change the hematocrit or the Hb levels in Wistar rats with renal anemia induced by 600 mg/kg/day of adenine. Plasma erythropoietin concentrations were also not different between luseogliflozin- and vehicle-treated rats. Similarly, in human erythropoietin-producing cells derived from pluripotent stem cells, luseogliflozin treatment did not change the erythropoietin level in the medium. Conclusions: These data suggest that SGLT2 inhibitor fails to exert hematopoietic effects in non-diabetic conditions. Keywords: Erythropoietin; Renal anemia; Sodium-glucose cotransporter 2 inhibitor (医博甲751)

The mechanism of action of Spi-B in the transcriptional activation of the interferon-α4 gene 宮嵜 亮 Miyazaki Ryo
Abstract Plasmacytoid dendritic cells (pDCs) are characterized by an exclusive expression of nucleic acid sensing Toll-like receptor 7 (TLR7) and TLR9, and production of high amounts of type I interferon (IFN) in response to TLR7/9 signaling. This function is crucial for both antiviral immunity and the pathogenesis of autoimmune diseases. An Ets family transcription factor, i.e., Spi-B (which is highly expressed in pDCs) is required for TLR7/9 signal-induced type I IFN production and can transactivate IFN-α promoter in synergy with IFN regulatory factor-7 (IRF-7). Herein, we analyzed how Spi-B contributes to the transactivation of the Ifna4 promoter. We performed deletion and/or mutational analyses of the Ifna4 promoter and an electrophoretic mobility shift assay (EMSA) and observed an Spi-B binding site in close proximity to the IRF-7 binding site. The EMSA results also showed that the binding of Spi-B to the double-stranded DNA probe potentiated the recruitment of IRF-7 to its binding site. We also observed that the association of Spi-B with transcriptional coactivator p300 was required for the Spi-B-induced synergistic enhancement of the Ifna4 promoter activity by Spi-B. These results clarify the molecular mechanism of action of Spi-B in the transcriptional activation of the Ifna4 promoter. Keywords: IRF-7; Interferon-α; Plasmacytoid dendritic cell; Spi-B; p300 (医博甲750)

Overexpression of Antiapoptotic MCL-1 Predicts Worse Overall Survival of Patients With Non-small Cell Lung Cancer 中野 貴之 Nakano Takayuki
Abstract Background/aim: Myeloid cell leukemia-1 (MCL-1) is a member of the B-cell lymphoma-2 (Bcl-2) family of proteins, which regulate the intrinsic (mitochondrial) apoptotic cascade. MCL-1 inhibits apoptosis, which may be associated with resistance to cancer therapy. Therefore, in this study, the clinical role of MCL-1 in non-small cell lung cancer (NSCLC) was explored. Patients and methods: This retrospective study included 80 patients with stage 1-3A NSCLC, who underwent surgery without preoperative treatment between 2010 and 2011. MCL-1 expression and Ki-67 index were determined via immunohistochemical staining. Apoptotic index (AI) was determined via terminal deoxynucleotidyl transferase dUTP nick end labeling. Results: The receiver operating characteristic curve analysis (area under curve=0.6785) revealed that MCL-1 expression in 30.0% of the NSCLC tumor cells was a significant cut-off for predicting prognosis. Tumors were considered MCL-1-positive if staining was observed in >30% of the cells. Thirty-six tumors (45.0%) were MCL-1-positive. However, there were no significant differences between MCL-1 expression and clinical variables. AI was lower in MCL-1-positive (2.2±3.6%) than in MCL-1-negative (5.2±7.9%) tumors, although the difference was not significant (p=0.1080). The Ki-67 index was significantly higher in MCL-1-positive than in MCL-1-negative tumors (18.0% vs. 3.0%; p<0.001). Five-year survival rate was significantly worse in patients with MCL-1-positive tumors (68.3%) than in those with MCL-1-negative tumors (93.1%, p=0.0057). Univariate [hazard ratio (HR)=5.041, p=0.0013], and multivariate analyses revealed that MCL-1 expression was a significant prognostic factor (HR=3.983, p=0.0411). Conclusion: MCL-1 expression in NSCLC cells correlated inversely with AI and positively with Ki-67 index. MCL-1 may serve as a potential prognostic biomarker and a novel therapeutic target in NSCLC. Keywords: Apoptosis; myeloid cell leukemia-1; non-small cell lung cancer; prognosis; survival (医博甲749)

Light exercise without lactate elevation induces ischemic tolerance through the modulation of microRNA in the gerbil hippocampus 高田 忠幸 Takata Tadayuki
Abstract Previously we studied the possible neuroprotective effects of ischemia-resistant exercise in a gerbil model of transient whole-brain ischemia and evaluated the histology, expression of specific proteins, and brain function under different conditions. The present study investigated the neuroprotective effects of light exercise, without lactate elevation, in a gerbil model of ischemia/reperfusion injury. Transient whole-brain ischemia was induced by occlusion of the bilateral common carotid arteries for 5 min. A group of animals was subjected to treadmill exercise before ischemia induction. Hippocampal neuronal damage and miRNA expression, as well as behavioral deficits and plasma lactate levels, were evaluated. Light exercise suppressed hippocampal neuron loss and preserved short-term memory. Moreover, 14 miRNAs (mmu-miR-211-3p, -327, -451b, -711, -3070-3p, -3070-2-3p, -3097-5p, -3620-5p, -6240, -6916-5p, -6944-5p, 7083-5p, -7085-5p, and -7674-5p) were upregulated and 6 miRNAs (mmu-miR-148b-3p, -152-3p, -181c-5p, -299b-5p, -455-3p, and -664-3p) were downregulated due to ischemia. However, the expression of these miRNAs remained unchanged when animals performed light exercise before the ischemic event. Differentially expressed miRNAs regulate multiple biological processes such as inflammation, metabolism, and cell death. These findings suggest that light exercise reduces neuronal death and behavioral deficits after transient ischemia by regulating hippocampal miRNAs. Keywords: Hippocampus; Ischemic tolerance exercise; Lactate; MicroRNA; Reperfusion; Short-term memory; (医博甲748)

研究授業「企業論」 岡本 丈彦


「持続可能」の概念と企業 ―「 持続不可能 」を導く短絡思考についての一考察― 岡本 丈彦


建築模型の製作を通して学ぶ保育士の空間構成 岡谷 崇史


香川県郷土教育史研究序説(三) 溝渕 利博


小学校英語指導法についての一考察 ~児童の興味・関心を引く指導~ 竹田 忠弘


保育所や幼稚園等と小学校との連携・接続について-理解を深めていく授業展開についての考察- 佐々木 利子


プロスポーツチーム組織におけるフロントスタッフの役割と仕事:「ホームゲーム」の産出に着目して 宇野 博武


研究授業「教育学原論」の報告 相馬 宗胤


研究授業「文書実務」の実施報告 佐藤 麻衣


研究授業「医療秘書概論」の実施報告 秋鹿 悦子