ヒトORCタンパク質によるグアニン四重鎖DNAの認識に関する研究

京都大学新制・課程博士博士(エネルギー科学)甲第24326号エネ博第454号新制||エネ||85(附属図書館)京都大学大学院エネルギー科学研究科エネルギー基礎科学専攻(主査)教授 片平 正人, 教授 森井 孝, 教授 杤尾 豪人学位規則第4条第1項該当Doctor of Energy ScienceKyoto UniversityDGA

Diuresis and inversion therapy to improve clearance of lower caliceal stones after shock wave lithotripsy: A prospective, randomized, controlled, clinical study

Objective: To improve the clearance of lower caliceal stones (LCSs) after shock wave lithotripsy (SWL) using a combination of intra-operative forced diuresis and inversion therapy. Materials and Methods: One hundred and fifty-seven consecutive patients with symptomatic, single LCSs of 5-20 mm size were prospectively randomized into two groups. The first (study group, SG) underwent SWL at the time of the maximum diuresis with the patient in the Trendelenburg position with an angle of 30 degree, while the second group (control group, CG) underwent standard SWL. After the last SWL session, patients were followed-up regularly using plain abdominal X-ray and renal ultrasound. The primary endpoint of the study was the stone-free rate (SFR) at 12 weeks. Results: A total of 141 patients completed the study treatment protocol and follow-up: 69 patients in SG and 72 patients in CG. Both groups were comparable in baseline data. SG showed significantly higher SFR at all follow-up time points. At week 12, 78.3% of SG were rendered stone free, whereas only 61.1% were stone free in CG (P = 0.030). Also, there was a significantly higher SFR for larger stones (>10 mm) and stones with higher attenuation value (>500 Hounsfield units) in SG than CG. Mild non-significant complications were reported in both groups. Conclusion: SWL with intraoperative forced diuresis and inversion seems to be an effective measure with minimal extra cost to improve LCS clearance post-SWL

IL-13 Augments Histone Demethylase JMJD2B/KDM4B Expression Levels, Activity, and Nuclear Translocation in Airway Fibroblasts in Asthma

Purpose. Asthma is one of the most common obstructive pulmonary diseases worldwide. Epigenetic alterations, including DNA methylation and histone modifications, have been reported to contribute to asthma pathogenesis. Since the inflammation mediator and remodeling trigger, IL-13, is known to play a central role in the pathophysiology of asthma, this study was aimed to identify novel IL-13-regulated epigenetic modifiers in asthma that may contribute to subepithelial fibrosis. Methods. Publicly available transcriptomic datasets from Gene Expression Omnibus (GEO) were used to identify differentially expressed genes on an epigenetic level upon IL-13 exposure in lung fibroblasts. Bronchial fibroblasts isolated from healthy and asthmatic individuals were assessed for the gene and protein expression levels of the identified gene at baseline and upon IL-13 treatment using qRT-PCR and western blotting, respectively. Its subcellular localization and tissue distribution were examined in bronchial fibroblasts as well as bronchial biopsies by immunofluorescence and immunohistochemical analysis, respectively. Results. Bioinformatic analysis revealed the differential expression of the histone demethylase JMJD2B/KDM4B, a well-known epigenetic modulator that leads to the demethylation of different lysine residues on histones, in IL-13-treated lung fibroblasts. The baseline expression levels of JMJD2B were higher in asthmatic fibroblasts and in bronchial biopsies in comparison to healthy ones. There was also an increase in JMJD2B activity as evidenced by the demethylation of its downstream target, H3K36me3. Furthermore, IL-13 stimulation induced JMJD2B expression and further demethylation of H3K36me3 in asthmatic fibroblasts. This was accompanied by increased translocation of JMJD2B into the nucleus. Conclusion. This study highlights the novel pathological involvement of the histone demethylase JMJD2B/KDM4B in asthmatic airway fibroblasts that are regulated by IL-13. Clinical implications. Given that there is no single therapeutic medicine to effectively treat the various subtypes of asthma, this study provides promising insights into JMJD2B as a new therapeutic target that could potentially improve the treatment and management of asthma

Preoperative predictive parameters for accurate detection of stage IV endometriosis

Abstract Background Surgery is the main line of treatment of endometriosis. Patients with stage IV endometriosis have more extensive adhesions, which make the surgery difficult. There are no accurate non-invasive predictive preoperative parameters of stage IV endometriosis and no consensus has been reached. Therefore, the aim of the present study was to evaluate and detect preoperative non-invasive parameters for the detection of stage IV endometriosis. Patients and methods In the present study, we included 150 females admitted for surgical removal of endometriosis. We scored and classified endometriosis into four stages according to the revised ASRM classification. We compared between baseline characteristics of patients with different stages of endometriosis, and then we selected the best combination of diagnostic and predictive parameters of stage IV endometriosis. Results Predictors of stage IV endometriosis and indicators for safety surgery were as follows: VAS ≥ 4 (p < 0.001), fixed uterus (p = 0.005), fixed ovarian cysts (p < 0.001), tender uterosacral ligament nodule (p < 0.001), tender rectovaginal septum nodule (p = 0.003), bilateral endometriosis (p < 0.001), and sum of sizes of endometriotic nodules (p < 0.001). Conclusion Fixed uterus, fixed ovarian cysts, tender uterosacral ligament nodule, tender rectovaginal septum nodule, bilateral endometriosis, and indications for surgery were significantly considered adequate predictive markers for stage IV endometriosis

Effectiveness of the team-based learning (TBL) strategy on medical students' performance

Objectives: Team-based learning (TBL) represents a new and interesting educational strategy. It helps to enhance students' professional competencies and ideally works to prepare them in their pursuit of lifelong learning. The aim of this study is to evaluate the effectiveness of TBL as an educational strategy on medical students' performance in a problem-based learning (PBL) curriculum. Methods: A cross-sectional study was conducted through a self-designed questionnaire. It was constructed to examine several aspects of TBL, including cognition, social skills, high school educational system, and personal development. A total of 112 students were invited to participate in the study and 100 completed the survey. Individual-readiness assurance test (IRAT) and group-readiness assurance test (GRAT) scores were collected and the data were analysed and compared to the results of the final assessment using Statistical Package for the Social Sciences (SPSS). Results: A total of 52 students (52%) described TBL as fostering a cooperative learning environment and 64 students (64%) found the materials to be easier to understand when discussed among themselves as a group. Compared to final examination results, there was a significant correlation (p = 0.0001) between IRAT performance and final exam score. In addition, there was a significant correlation between high school education system and IRAT score, where the best performance was observed among students coming from schools using the British curriculum. Conclusions: The overall perception and attitude of students toward the TBL system was positive and promising. Nevertheless, there are some notes and areas of concern that must be re-examined and remedied to improve TBL as an educational tool

HLA Class II-DRB1 Alleles with Hepatitis C Virus Infection Outcome in Egypt: A Multicentre Family-based Study

Introduction and aim. Hepatitis C virus (HCV) infection is a global medical problem. HLA -DRB1 alleles have an important role in immune response against HCV. The aim of this study is to clarify the contribution of HLA -DRB1 alleles in HCV susceptibility in a multicentre family-based study.Material and methods. A total of 162 Egyptian families were recruited in this study with a total of 951 individuals (255 with chronic hepatitis C (CHC), 588 persons in the control group(-ve household contact to HCV) and 108 persons who spontaneously cleared the virus (SVC). All subjects were genotyped for HLA -DRB1 alleles by SSP-PCR and sequence based typing (SBT) methods.Results. The carriage of alleles 3:01:01 and 13:01:01 were highly significant in CHC when compared to that of control and SVC groups [OR of 3 family = 5.1289, PC (Bonferroni correction ) = 0.0002 and 5.9847, PC = 0.0001 and OR of 13 family = 4.6860, PC = 0.0002 and OR = 6.5987, PC = 0.0001 respectively]. While DRB1*040501, DRB1*040101, DRB1*7:01:01 and DRB1*110101 alleles were more frequent in SVC group than CHC patients (OR = 0.4052, PC = 0.03, OR: OR = 0.0916,PC = 0.0006, OR = 0.1833,PC = 0.0006 and OR = 0.4061, PC = 0.0001 respectively).Conclusions. It was concluded that among the Egyptian families, HLA-DRB1*030101, and DRB1*130101 alleles associated with the risk of progression to CHC infection, while DRB1*040101, DRB1*040501, DRB1*7:01:01and DRB1*110101 act as protective alleles against HCV infection

Mixed Contaminants: Occurrence, Interactions, Toxicity, Detection, and Remediation

The ever-increasing rate of pollution has attracted considerable interest in research. Several anthropogenic activities have diminished soil, air, and water quality and have led to complex chemical pollutants. This review aims to provide a clear idea about the latest and most prevalent pollutants such as heavy metals, PAHs, pesticides, hydrocarbons, and pharmaceuticals&mdash;their occurrence in various complex mixtures and how several environmental factors influence their interaction. The mechanism adopted by these contaminants to form the complex mixtures leading to the rise of a new class of contaminants, and thus resulting in severe threats to human health and the environment, has also been exhibited. Additionally, this review provides an in-depth idea of various in vivo, in vitro, and trending biomarkers used for risk assessment and identifies the occurrence of mixed contaminants even at very minute concentrations. Much importance has been given to remediation technologies to understand our current position in handling these contaminants and how the technologies can be improved. This paper aims to create awareness among readers about the most ubiquitous contaminants and how simple ways can be adopted to tackle the same