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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
3.
4.
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
5.
Yosuke Homma Takashi Shiga Hiraku Funakoshi Dai Miyazaki Atsushi Sakurai Yoshio Tahara Ken Nagao Naohiro Yonemoto Arino Yaguchi Naoto Morimura 《The American journal of emergency medicine》2019,37(2):241-248
Objective
This study assessed the association between the timing of first epinephrine administration (EA) and the neurological outcomes following out-of-hospital cardiac arrests (OHCAs) with both initial shockable and non-shockable rhythms.Methods
This was a post-hoc analysis of a multicenter prospective cohort study (SOS-KANTO 2012), which registered OHCA patients in the Kanto region of Japan from January 2012 to March 2013. We included consecutive adult OHCA patients who received epinephrine. The primary result included 1-month favorable neurological outcomes defined as cerebral performance category (CPC) 1 or 2. Secondary results included 1-month survival and return of spontaneous circulation (ROSC) after arrival at the hospital. Multivariable logistic regression analysis determined the association between delay per minute of the time from call to first EA in both pre- or in-hospital settings and outcomes.Results
Of the 16,452 patients, 9344 were eligible for our analyses. In univariable analysis, the delay in EA was associated with decreased favorable neurological outcomes only when the initial rhythm was a non-shockable rhythm. In multivariable analyses, delay in EA was associated with decreased ROSC (adjusted odds ratio [OR] for one minute delay, 0.97; 95% confidence interval [CI], 0.96–0.98) and 1-month survival (adjusted OR, 0.95; 95% CI, 0.92–0.97) when the initial rhythm was a non-shockable rhythm, whereas during a shockable rhythm, delay in EA was not associated with decreased ROSC and 1-month survival.Conclusions
While assessing the effectiveness of epinephrine for OHCA, we should consider the time-limited effects of epinephrine. Additionally, consideration of early EA based on the pathophysiology is needed. 相似文献6.
7.
Yasushi Sawayama Hidehiro Itonaga Takuya Fukushima Nobuaki Nakano Hiroshi Fujiwara Atae Utsunomiya Takahiro Fukuda Toshihiro Miyamoto Tetsuya Eto Kaname Miyashita Hirohisa Nakamae Masao Ogata Atsushi Yamanoha Yasuhiko Miyazaki Junya Kanda Yoshiko Atsuta Koji Kato ATL Working Group of the Japan Society for Hematopoietic Cell Transplantation 《American journal of hematology》2019,94(5):E143-E146
8.
9.
Yosiaki Yajima Nobutaka Takahashi Atsusi Miyazaki Ryosuke Kikuchi Keisuke Kakisaka Keisuke Oikawa Kazuhiko Sugawara Yoshiki Eda Hiroshi Naganuma Masamitsu Unagami 《Nihon Shokakibyo Gakkai zasshi》2006,103(5):515-522
From April 1989 to December 2004, we performed liver biopsy on 475 patients and obtained biopsy proven 35 cases of non-alcoholic fatty liver. Among them, 18 cases were diagnosed as non-alcoholic steatohepatitis (NASH). During the last three years, we have tried to detect NASH using ultrasonography and elevated value of serum ferritin (> 300 ng/ml). All of the eligible 7 cases biopsied during the course were diagnosed as NASH. In these 7 cases, ALT levels improved after the body weight loss accompanied by the parallel decrease of serum ferritin levels. Measurement of serum ferritin is useful in the detection of NASH but the normal value of ferritin cannot rule out the possibility of NASH. 相似文献
10.
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