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1.
Daisuke Ishibashi Takeshi Ishikawa Satoshi Mizuta Hiroya Tange Takehiro Nakagaki Tsuyoshi Hamada Noriyuki Nishida 《Neurotherapeutics》2020,17(4):1836
The accumulation of abnormal prion protein (PrPSc) produced by the structure conversion of PrP (PrPC) in the brain induces prion disease. Although the conversion process of the protein is still not fully elucidated, it has been known that the intramolecular chemical bridging in the most fragile pocket of PrP, known as the “hot spot,” stabilizes the structure of PrPC and inhibits the conversion process. Using our original structure-based drug discovery algorithm, we identified the low molecular weight compounds that predicted binding to the hot spot. NPR-130 and NPR-162 strongly bound to recombinant PrP in vitro, and fragment molecular orbital (FMO) analysis indicated that the high affinity of those candidates to the PrP is largely dependent on nonpolar interactions, such as van der Waals interactions. Those NPRs showed not only significant reduction of the PrPSc levels but also remarkable decrease of the number of aggresomes in persistently prion-infected cells. Intriguingly, treatment with those candidate compounds significantly prolonged the survival period of prion-infected mice and suppressed prion disease-specific pathological damage, such as vacuole degeneration, PrPSc accumulation, microgliosis, and astrogliosis in the brain, suggesting their possible clinical use. Our results indicate that in silico drug discovery using NUDE/DEGIMA may be widely useful to identify candidate compounds that effectively stabilize the protein.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00903-9) contains supplementary material, which is available to authorized users. 相似文献
2.
Masaru Sasaki Tsuyoshi Takahashi Soichiro Funaki Koji Tanaka Yasuhiro Miyazaki Naoko Ose Tomoki Makino Yukinori Kurokawa Makoto Yamasaki Kiyokazu Nakajima Yasushi Shintani Masaki Mori Yuichiro Doki 《Asian journal of endoscopic surgery》2021,14(1):116-119
We report a case of a diaphragmatic hernia after a heart transplant operation. A 43-year-old woman, who underwent orthotropic heart transplantation for hypertrophic cadiomyopathy two year earlier, presented with vomiting and epigastric pain. A computed tomography scan showed that the stomach and transverse colon were dislocated in the left thoracic cavity. We diagnosed left diaphragmatic hernia incarceration and performed laparoscopic repair of the diaphragmatic hernia. A 12 × 8 cm diaphragmatic defect was found intraoperatively on the ventrolateral aspect of the left diaphragm, and the stomach with volvulus had herniated into the thorax through the defect. The hernia was considered to be iatrogenic. The diaphragmatic defect was large, and the diaphragm was thinning. We closed the defect by mesh repair. Laparoscopic mesh repair of the diaphragmatic hernia could be performed safely and with minimal invasiveness. 相似文献
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Yohei Tomaru Hiroshi Kamada Yuta Tsukagoshi Shogo Nakagawa Kenta Tanaka Ryoko Takeuchi Yuki Mataki Shumpei Miyakawa Masashi Yamazaki 《Journal of orthopaedic science》2019,24(1):159-165
Background
On April 1, 2016, the Ministerial ordinance was enforced, and musculoskeletal examination of the extremities was made mandatory. From 2008, the University of us started musculoskeletal direct examination. To expand the examination, from 2016, we started to use the marksheet-type questionnaire. This study aimed to report the results of a musculoskeletal examination and investigate the association between musculoskeletal examination and age/gender and reports the reliability of the collected questionnaire data.Methods
Direct musculoskeletal examination was performed in K school by 7 orthopedic surgeons. A marksheet-type screening questionnaire was distributed to all the elementary and junior high school students in Tsukuba and Hitachiomiya cities. The rates of abnormal findings for scoliosis, standing flexion, full squatting with the heels on the floor, general joint laxity, and standing on one leg, torticollis, and flat feet were calculated. We compared the results of the questionnaire and direct examination and calculated sensitivity, specificity, and odds ratio.Results
A total of 1844 students in K school had direct examination, and 22,494 questionnaires were able to correct in Tsukuba and Hitachiomiya cities. The rates of abnormal findings in direct examination/questionnaire in scoliosis, standing flexion, full squat, general joint laxity, standing on one leg, torticollis and flat foot were 18.7% (344/1842)/5.1% (1094/21441), 20.2% (372/1841)/26.6% (5817/22078), 6.2% (114/1832)/6.9% (1516/22101), 7.5% (1648/22252), 4.9% (1100/22077), 2.2% (31/1844)/1.2% (272/21687), and 12.5% (231/1842)/8.7% (1785/20871), respectively. Sensitivities of the questionnaire for scoliosis, stand flexion, full squatting, torticollis, and flat feet were 16.8% (53/316), 67.9% (250/368), 48.2% (55/114), 18.9% (7/37), and 32.2% (65/202), respectively.Conclusion
We reported the result of musculoskeletal examination. Accuracy and reliability of this questionnaire were not satisfactory. To perform high quality musculoskeletal examinations, we will aim to increase the quality of screening methods. 相似文献5.
Hiroto Kinoshita Hitomi Nishioka Aya Ikeda Kyoko Ikoma Yoichi Sameshima Hidehisa Ohi Mizuki Tatsuno Junka Kouyama Chiaki Kawamoto Tomohiro Mitsui Yuko Tamura Yu Hashimoto Masashi Nishio Tsuyoshi Ogashiwa Yusuke Saigusa Shin Maeda Hideaki Kimura Reiko Kunisaki Kazuhiko Koike 《Journal of gastroenterology and hepatology》2019,34(11):1929-1939
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Ichiro Yasuda Takuji Iwashita Takaya Ohnishi Tsuyoshi Mukai Masamichi Enya Eiichi Tomita Hisataka Moriwaki 《Digestive endoscopy》2006,18(Z1):S92-S95
Endoscopic nasobiliary drainage (ENBD) is a well established mode of biliary decompression. Although ENBD is certainly an uncomfortable procedure with the potential risk of spontaneous dislocation or removal of the drainage catheter by disoriented patients, it has several advantages over endoscopic biliary drainage (EBD) using an indwelling stent. The current indications for ENBD are: (i) temporary drainage to treat obstructive jaundice and cholangitis caused by malignant or benign biliary stricture; (ii) urgent drainage to treat suppurative cholangitis primarily caused by common bile duct stones; (iii) temporary drainage after stone removal in patients with suspected incomplete clearance and/or with cholangitis; and (iv) biliary leaks that occur primarily after surgery, as well as other indications. Different types of nasobiliary catheters are currently available that have been designed with various diameters, shapes, and materials. However, the current catheters are not considered by most endoscopists to be sufficient. Further improvements are needed to achieve better drainage and better maneuverability. 相似文献
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9.
Kentaroh Miyoshi Minoru Naito Tsuyoshi Ueno Shinji Hato Hideo Ino 《General thoracic and cardiovascular surgery》2009,57(11):629-632
A benign esophageal leiomyoma with abnormally increased fluorine-18-fluorodeoxyglucose uptake on positron emission tomography
(PET) was resected thoracoscopically. The tumor, of which the maximum standardized uptake value of the lesion was 4.7, was
well defined and 38 mm in diameter. Neither mitotic activity nor degeneration was found histologically; and immunoreactivity
for CD34, CD117, MIB-1, and glucose transporter-1 was negative immunohistochemically. A diagnosis of gastrointestinal stromal
tumor was ruled out by an oncogenic kinase gene mutation study. This case cautions against PET-dependent evaluation for malignant
potential of esophageal submucosal tumors. 相似文献
10.
For monitoring the changes in intracellular free Ca2+ concentration ([Ca2+]i), we developed a simple system combining a fluorescence microscope, an image intensifier, a video-camera, a cathode ray tube display and a photodiode, employing quin2 as a Ca2+ indicator. We recorded increases of the fluorescence intensity due to [Ca2+]i rises, when high K+ medium, neurotransmitter and Ca2+ ionophore were applied to the single cells of nervous system origin in culture. The present system is capable of simultaneous detection of the [Ca2+]i changes from multiple separate cells. 相似文献