パキコロイド血管新生症の特徴

京都大学新制・課程博士博士(医学)甲第23087号医博第4714号新制||医||1050(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 木村 剛, 教授 YOUSSEFIAN Shohab, 教授 大森 孝一学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

非心臓手術において、術前・術中の利尿剤投与が術後急性腎障害と有意に関連するが、レニンーアンギオテンシン系の阻害薬は有意に関連しない。後ろ向きコホート研究

BACKGROUND AND OBJECTIVES: Pre- and/or intra-operative use of diuretics, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) constitutes a potentially modifiable risk factor for postoperative acute kidney injury (AKI). It has been studied whether use of these drugs predicts AKI after cardiac surgery. The objective of this study was to examine whether administration of these agents was independently associated with AKI after non-cardiac surgery.　DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This was a retrospective observational study. Inclusion criteria were adult patients (age ≥ 18) who underwent non-cardiac surgery under general anesthesia from 2007 to 2009 at Kyoto Katsura Hospital. Exclusion criteria were urological surgery, missing creatinine values, and preoperative dialysis. The exposures of interest were pre- and/or intra-operative use of diuretics or ACE-I/ARB. Outcome variables were postoperative AKI as defined by the AKI Network (increase in creatinine ≥ 0.3 mg/dL or 150% within 48 hours, or urine output 6 hours). Multivariable logistic regression analyses were conducted and adjusted for potential confounders. Propensity scores (PS) for receiving diuretics or ACE-I/ARB therapy were estimated and PS adjustment, PS matching, and inverse probability weighting were performed.　RESULTS: There were 137 AKI cases (5.0%) among 2,725 subjects. After statistical adjustment for patient and surgical characteristics, odds (95% CI) of postoperative AKI were 2.07 (1.10-3.89) (p = 0.02) and 0.89 (0.56-1.42) (p = 0.63) in users of diuretics and ACE-I/ARB, respectively, compared with non-users. PS adjustment, PS matching, and inverse probability weighting yielded similar results. The effect size of diuretics was significantly greater in the patients with lower propensity for diuretic use (p for interaction < 0.1).　CONCLUSIONS: Prescription of diuretics, but not ACE-I/ARB, was independently associated with postoperative AKI after non-cardiac surgery, especially in patients with low propensity for diuretic use. It might be reasonable to withhold preoperative diuretics in these patients.博士（医学）・乙第1409号・平成29年11月24日Copyright: © 2015 Tagawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Choriocapillaris flow deficit in a pachychoroid spectrum disease using en face optical coherence tomography angiography averaging

[Purpose] To investigate the choriocapillaris changes associated with pachychoroid pigment epitheliopathy (PPE) in comparison with healthy eyes. [Methods] Nine 3 × 3 mm macular optical coherence tomography angiography images were acquired in patients with PPE and age-matched healthy participants. Multiple en face image averaging of the choriocapillaris was binarized for quantitative image analysis of the flow voids. In PPE eyes, we evaluated the presence of pachyvessels and the association between the location of the choriocapillaris flow deficit and pachyvessels. [Results] Thirty-two eyes with PPE and 30 eyes of healthy participants were included. In PPE eyes, the mean total area (1.16 ± 0.18 vs. 0.91 ± 0.16, p < 0.001) and average size of the flow voids (790 ± 144 vs. 520 ± 138; p < 0.001) were significantly larger than those in control eyes. Composite images of the choriocapillaris and choroid showed choriocapillaris flow deficits just above and outside the pachyvessels. The mean proportion of the flow void area overlying the pachyvessels against the whole flow void area of the choriocapillaris was 21.3% ± 10.2% (9.38%-44.42%) in PPE eyes. [Conclusions] In PPE eyes, the blood flow area of the choriocapillaris decreased diffusely within the macular area compared to control eyes, and the choriocapillaris flow deficit was not necessarily related to pachyvessel location

Bortezomib Reduces the Tumorigenicity of Multiple Myeloma via Downregulation of Upregulated Targets in Clonogenic Side Population Cells

Side population (SP) cells in cancers, including multiple myeloma, exhibit tumor-initiating characteristics. In the present study, we isolated SP cells from human myeloma cell lines and primary tumors to detect potential therapeutic targets specifically expressed in SP cells. We found that SP cells from myeloma cell lines (RPMI 8226, AMO1, KMS-12-BM, KMS-11) express CD138 and that non-SP cells include a CD138-negative population. Serial transplantation of SP and non-SP cells into NOD/Shi-scid IL-2 gamma nul mice revealed that clonogenic myeloma SP cells are highly tumorigenic and possess a capacity for self-renewal. Gene expression analysis showed that SP cells from five MM cell lines (RPMI 8226, AMO1, KMS-12-BM, KMS-11, JJN3) express genes involved in the cell cycle and mitosis (e. g., CCNB1, CDC25C, CDC2, BIRC5, CENPE, SKA1, AURKB, KIFs, TOP2A, ASPM), polycomb (e. g., EZH2, EPC1) and ubiquitin-proteasome (e. g., UBE2D3, UBE3C, PSMA5) more strongly than do non-SP cells. Moreover, CCNB1, AURKB, EZH2 and PSMA5 were also upregulated in the SPs from eight primary myeloma samples. On that basis, we used an aurora kinase inhibitor (VX-680) and a proteasome inhibitor (bortezomib) with RPMI 8226 and AMO1 cells to determine whether these agents could be used to selectively target the myeloma SP. We found that both these drugs reduced the SP fraction, though bortezomib did so more effectively than VX-680 due to its ability to reduce levels of both phospho-histone H3 (p-hist. H3) and EZH2; VX-680 reduced only p-hist. H3. This is the first report to show that certain oncogenes are specifically expressed in the myeloma SP, and that bortezomib effectively downregulates expression of their products. Our approach may be useful for screening new agents with which to target a cell population possessing strong tumor initiating potential in multiple myeloma

Heat-resistant DNA tile arrays constructed by template-directed photoligation through 5-carboxyvinyl-2′-deoxyuridine

Template-directed DNA photoligation has been applied to a method to construct heat-resistant two-dimensional (2D) DNA arrays that can work as scaffolds in bottom-up assembly of functional biomolecules and nano-electronic components. DNA double-crossover AB-staggered (DXAB) tiles were covalently connected by enzyme-free template-directed photoligation, which enables a specific ligation reaction in an extremely tight space and under buffer conditions where no enzymes work efficiently. DNA nanostructures created by self-assembly of the DXAB tiles before and after photoligation have been visualized by high-resolution, tapping mode atomic force microscopy in buffer. The improvement of the heat tolerance of 2D DNA arrays was confirmed by heating and visualizing the DNA nanostructures. The heat-resistant DNA arrays may expand the potential of DNA as functional materials in biotechnology and nanotechnology

Mutant huntingtin impairs Ku70-mediated DNA repair

Mutant huntingtin prevents interaction of the DNA damage repair complex component Ku70 with damaged DNA, blocking repair of double-strand breaks

チイキ ノ ツヨミ ヲ タカメル コウシュウ エイセイ カンゴ ギジュツ ヲ シュウトク スル シミュレーション プログラム WEB フキュウバン ノ ジツヨウセイ ニ カンスル イケン シュウシュウ チョウサ

【目的】地域の強みを高める公衆衛生看護技術（以下技術）を習得するシナリオベースのシミュレーションプログラムのWEB 普及版（以下WEB 普及版）の実践現場での実用性について、意見を収集することである。【方法】研究参加者は、全国の子育て世代包括支援センターと地域包括支援センター20施設に勤務する常勤保健師24名であり、2020年度、プログラム体験前後に、質問紙にて意見収集調査を行った。【結果】研究参加者は年齢・経験ともに幅広い層であり、WEB 普及版が有効かを尋ねたところ、9割以上が、とてもそう思う、そう思うと回答していた。また、技術習得のためにシミュレーションを用いることが有効かについては、プログラムを体験した全員が、とてもそう思う、そう思うと回答しており、自由記載でもプログラムについて、効果を感じているという意見があった。プログラム体験後の各技術の実施度得点と自信度得点は、ともに合計点と1項目を除く下位項目で、体験前より高値を示し、22項目中8項目で有意差が見られた（P<0.05）。【結論】本プログラムのWEB 普及版には一定の汎用性と実用性があことが示唆された。研究報告Report