外来診断を可能にするモバイルテクノロジーを用いた細径子宮鏡の使用実績と診断精度の検討

Office hysteroscopy is a minimally invasive procedure and provides a direct view of the endometrial cavity. This study presents the first report of a novel smartphone‑based ultrathin flexible hysterofiberscopy system (currently known as office diagnostic smart hysterofiberscopy, or Hysmartscopy), for the diagnosis of intrauterine abnormalities. The Hysmartscopy system captures images using a flexible fiberscope (0.8 mm in diameter) coupled with an Apple iPhone 6S™. This study was conducted at the Department of Gynecology of Nara Medical University Hospital from February, 2015 to February, 2019. In total, 22 patients requiring a diagnostic Hysmartscopy for the investigation of intrauterine pathology were included in this study. In the first cohort, Hysmartscopy was performed in the operating room with anesthesia in 17 patients to assess the overall physician's experience during image acquisition, subjective image quality and the ease of use on a 5‑point Likert scale. In the second cohort, 5 subjects further underwent Hysmartscopy without anesthesia to evaluate the feasibility and safety of this system. Images were assessed by two expert gynecological endoscopists blinded to the pathological reports. The Hysmartscopy system revealed good resolutions in the ex vivo image and color resolution. From the beginning of the procedure, the time required to capture a video was <1 min. The ergonomic advantage of this technique enabled the examiners to use direct visualization for image‑guided diagnosis in a hand‑held manner. On average, the quality of the images (4.0/5.0 on a 5‑point Likert scale) may be largely sufficient to detect emergent findings. The diagnostic accuracy of Hysmartscopy was found to be 100% (2/2) for the normal endometrium, 71.4% (5/7) for endometrial polyps, 62.5% (5/8) for submucosal fibroids and 100% (5/5) for endometrial cancer. The diagnostic accuracy of Hysmartscopy was 77.3%. None of the cases had any complications during and after the diagnostic procedures. Thus, the results indicate that Hysmartscopy is a patient‑friendly technique without the need for anesthesia and cervical dilation in an office setting. To the best of our knowledge, this study is first proof of concept pilot study of Hysmartscopy. Hysmartscopy may prove to be a simple, convenient, non‑invasive, accurate and well‑tolerated procedure for the diagnosis of intrauterine abnormalities that can be performed within an outpatient clinic.博士（医学）・乙第1453号・令和2年3月16日Copyright: © Iwai et al. This is an open access article distributed under theterms of CreativeCommons Attribution License (https://creativecommons.org/licenses/by-nc-nd/4.0/)

卵巣明細胞癌と類内膜癌の鑑別に関するMRIについての知見

BACKGROUND: Common cancerous histological types associated with endometriosis are clear cell carcinoma (CCC) and endometrioid carcinoma (EC). CCC is regarded as an aggressive, chemoresistant histological subtype. Magnetic resonance imaging (MRI) offers some potential advantages to diagnose ovarian tumors compared with ultrasonography or computed tomography. This study aimed to identify MRI features that can be used to differentiate between CCC and EC. METHODS: We searched medical records of patients with ovarian cancers who underwent surgical treatment at Nara Medical University Hospital between January 2008 and September 2018; we identified 98 patients with CCC or EC who had undergone preoperative MRI. Contrasted MRI scans were performed less than 2 months before surgery. Patients were excluded from the study if they had no pathology, other pathological subtype of epithelial ovarian cancer, and/or salvage treatment for recurrence and metastatic ovarian cancer at the time of study initiation. Clinically relevant variables that were statistically significant by univariate analysis were selected for subsequent multivariate regression analysis to identify independent factors to distinguish CCC from EC. RESULTS: MRI of CCC and EC showed a large cystic heterogeneous mixed mass with mural nodules protruding into the cystic space. Univariate logistic regression analysis revealed that the growth pattern (broad-based nodular structures [multifocal/concentric sign] or polypoid structures [focal/eccentric sign]), surface irregularity (a smooth/regular surface or a rough/irregular/lobulated surface), "Width" of mural nodule, "Height-to-Width" ratio (HWR), and presence of preoperative ascites were factors that significantly differed between CCC and EC. In the multivariate logistic regression analysis, the growth pattern of the mural nodule (odds ratio [OR] = 0.69, 95% confidence interval [CI]: 0.013-0.273, p = 0.0004) and the HWR (OR = 3.71, 95% CI: 1.128-13.438, p = 0.036) were independent predictors to distinguish CCC from EC. CONCLUSIONS: In conclusion, MRI data showed that the growth pattern of mural nodules and the HWR were independent factors that could allow differentiation between CCC and EC. This finding may be helpful to predict patient prognosis before operation.博士（医学）・乙第1433号・令和元年9月27日© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Exosomes in Cancer Diagnosis and Radiation Therapy

Exosomes are a subgroup of extracellular vesicles that are released by all types of cells, including tumor cells, and mediate intercellular communication via the transport of various intracellular components, including microRNAs, messenger RNAs, and proteins. Radiation produces reactive oxygen species and induces DNA double-strand break in cancer cells and normal cells. Cancer cells have severe damage and die by irradiation, but normal cells can keep proliferation with their high DNA repair ability. Irradiated cells generate communication signals and cause biological changes in neighboring or distant non-irradiated cells. This review outlines the role of exosomes in radiation therapy. In the tumor microenvironment, exosomes are considered to regulate cell survival, migration, and resistance to therapy by interacting with vascular endothelial cells and various types of immune cells. Nowadays, radiation therapy is typically combined with immunotherapy. Regulation of the activity of exosomes may overcome the problem of resistance to immunotherapy. Furthermore, exosomes can attenuate resistance to chemotherapy by transporting certain types of microRNA. The current evidence suggests that exosomes may be useful in the diagnosis and treatment of cancer in the future

Calpain-specific breakdown fragment in human drusen

Purpose. With aging and age-related macular dystrophy (AMD), proteolytic fragments are deposited in extracellular drusen located between the RPE and Bruch’s membrane. Localized hypoxia may be a risk factor for AMD. Our hypothesis is that following hypoxia, activation of proteolytic enzymes called calpains may cause proteolysis/degeneration of retinal cells and RPE. No direct evidence has yet demonstrated activation of calpains in AMD. The purpose of the present study was to identify calpain-cleaved proteins in drusen. Methods. Seventy-six (76) drusen were analyzed in human eye sections from six normal and twelve AMD human donor eyes. The sections were subjected to immunofluorescence for the calpain-specific 150 kDa breakdown product from α-spectrin, SBDP150-a marker for calpain activation, and for recoverin-a marker for photoreceptor cells. Results. Among 29 nodular drusen, 80% from normal eyes and 90% from AMD eyes stained positive for SBDP150. Among 47 soft drusen, mostly from AMD eyes, 72% stained positive for SBDP150. Thus, the majority of both soft and nodular drusen from AMD donors contained SBDP150. Conclusions. SBDP150 was detected for the first time in soft and nodular drusen from human donors. Our results suggest that calpain-induced proteolysis participates in the degeneration of photoreceptors and/or RPE cells during aging and AMD. Calpain inhibitors may ameliorate AMD progressio

子宮内膜側に発症する (Subtypel) 子宮腺筋症は黄体ホルモン療法による多量性器出血の危険因子である

We aimed to retrospectively analyze the risk factors of a continuous dienogest (DNG) therapy for serious unpredictable bleeding in patients with symptomatic adenomyosis. This is a retrospective study based on data extracted from medical records of 84 women treated with 2 mg of DNG orally each day between 2008 and 2017. 47 subjects were excluded from the original analyses due to an inadequate subcategorization into subtype I and subtype II and a lack of hemoglobin levels. The influence of various independent variables on serious unpredictable bleeding was assessed. Of the 37 eligible patients who received the continuous DNG therapy, 14 patients experienced serious unpredictable bleeding. Univariate analysis revealed that the serious bleeding group had subtype I adenomyosis (P = 0.027). There was no correlation between age, parity, minimum hemoglobin level before treatment, previous endometrial curettage, and duration of DNG administration, or uterine or adenomyosis size and the serious bleeding. A DNG-related serious unpredictable bleeding is associated with the structural type of adenomyosis (subtype I) in patients with symptomatic adenomyosis.博士（医学）・甲第800号・令和3年9月29日© The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

ウリジン二リン酸グルクロン酸転移酵素1A1の立体構造予測

In this study,we construct the three dimensional structure of Uridine Diphosphate Glucuronosyltransferate (UGT) 1A1 by using for template homology/analyogy recognition engine (phyre) server.Ten PDB entries including UGT2B7 were used for template of the model,and both UDP-glucuronic acid binding domain and substrate binding domain were obtained. By using the modeled structure,structural refinement was carried out by molecular dynamics (MD) simulations.In order to investigate the role of cysteine,MD simulations of both UGT1A1 models with and without the Cys127-Cys156 disulfide bond were performed.As the results of the simulations,structural features of UGT1A1 can be investigated, and refined structure of it was obtained

明示的に水を取り扱った分子動力学シュミレーションの変異体の計算に対する有用性の検討.Bovine Pancreatic Trypsin Inhibitorを用いた試験

Computational simulations can reproduce or predict structural changes of proteins upon various mutations in a short time.In this study,molecular dynamics simulations of the wild type and mutants of bovine pancreatic trypsin inhibitor with explicit solvent were carried out to evaluate reliability of molecular dynamics simulation.We used two force fields,ff03 and ff99SB,and compared the results.Effects of the amino acid mutations on structural stability were largely reproduced by the simulations

CO Multi-line Imaging of Nearby Galaxies (COMING). IX. 12^{12}CO(JJ=2-1)/12^{12}CO(JJ=1-0) line ratio on kiloparsec scales

While molecular gas mass is usually derived from $^{12}$CO($J$=1-0) - the most fundamental line to explore molecular gas - it is often derived from $^{12}$CO($J$=2-1) assuming a constant $^{12}$CO($J$=2-1)/$^{12}$CO($J$=1-0) line ratio ($R_{2/1}$). We present variations of $R_{2/1}$ and effects of the assumption that $R_{2/1}$ is a constant in 24 nearby galaxies using $^{12}$CO data obtained with the Nobeyama 45-m radio telescope and IRAM 30-m telescope. The median of $R_{2/1}$ for all galaxies is 0.61, and the weighted mean of $R_{2/1}$ by $^{12}$CO($J$=1-0) integrated-intensity is 0.66 with a standard deviation of 0.19. The radial variation of $R_{2/1}$ shows that it is high (~0.8) in the inner ~1 kpc while its median in disks is nearly constant at 0.60 when all galaxies are compiled. In the case that the constant $R_{2/1}$ of 0.7 is adopted, we found that the total molecular gas mass derived from $^{12}$CO($J$=2-1) is underestimated/overestimated by ~20%, and at most by 35%. The scatter of a molecular gas surface density within each galaxy becomes larger by ~30%, and at most by 120%. Indices of the spatially resolved Kennicutt-Schmidt relation by $^{12}$CO($J$=2-1) are underestimated by 10-20%, at most 39% in 17 out of 24 galaxies. $R_{2/1}$ has good positive correlations with star-formation rate and infrared color, and a negative correlation with molecular gas depletion time. There is a clear tendency of increasing $R_{2/1}$ with increasing kinetic temperature ($T_{\rm kin}$). Further, we found that not only $T_{\rm kin}$ but also pressure of molecular gas is important to understand variations of $R_{2/1}$. Special considerations should be made when discussing molecular gas mass and molecular gas properties inferred from $^{12}$CO($J$=2-1) instead of $^{12}$CO($J$=1-0).Comment: 29 pages, 18 figures, 5 tables. Accepted for publication in PASJ. The original resolution version is available here (https://astro3.sci.hokudai.ac.jp/~radio/coming/publications/COMING_IX_org_res.pdf