300 research outputs found

    Cholesterol markedly reduces ion permeability induced by membrane-bound amphotericin B

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    AbstractIt is widely accepted that amphotericin B (AmB) together with sterol makes a mixed molecular assemblage in phospholipid membrane. By adding AmB to lipids prior to preparation of large unilamellar vesicles (LUV), we directly measured the effect of cholesterol on assemblage formation by AmB without a step of drug's binding to phospholipid bilayers. Potassium ion flux assays based on 31P-nuclear magnetic resonance (NMR) clearly demonstrated that cholesterol markedly inhibits ion permeability induced by membrane-bound AmB. This could be accounted for by a membrane-thickening effect of cholesterol since AmB actions are known to be markedly affected by the thickness of membrane. Upon addition of AmB to an LUV suspension, the ion flux gradually increased with increasing molar ratios of cholesterol up to 20 mol%. These biphasic effects of cholesterol could be accounted for, at least in part, by the ordering effect of cholesterol

    Activity concentration of Fukushima-derived radiocesium in the western subarctic area of the North Pacific Ocean in summer 2017

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    Vertical profiles of radiocesium (134Cs and 137Cs) were measured in the western subarctic area of the North Pacific in 2017. The highest concentration of 134Cs, which was derived from the accident of the Fukushima Dai-ichi Nuclear Power Plant in 2011, was 0.14 Bq m−3 (or 1.19 Bq m−3 after the decay correction to the accident date). Although the vertical inventory of 134Cs decreased between 2014 and 2017, the inventory in 2017 was larger than that expected. That was probably arose from the return of some portion of the high-concentration water mass along with the anticlockwise subarctic gyre current

    Global nutrients data synthesis based on Reference Material of Nutrients of Seawater

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    Realistic distributions of nitrate, phosphate and silicate and inventories of them in the world’s ocean are basic issues of geochemical study of nitrogen, phosphorous and silicon cycles as well as tracer use of nutrients for deep ocean circulation. WOA09 and WGHC were global hydrographic datasets created by objective analysis and offset correction/objective analysis, respectively. However synthesis using mathematics methods and experience could get apparent global comparability but does not have a firm foundation, therefore accuracy is unknown for nutrients data inWOA05/09 and WGHC. Recently hydrographic dataset such as CARINA and PACIFICA were also created by synthesis. We did global synthesis work based on Reference Material of Nutrients in Seawater (RMNS) for WOCE/CLIVAR cruises datasets, WGHC datasets and some new hydrographic cruises which cover the Pacific Ocean, the Atlantic Ocean, the Indian Ocean, the Southern Ocean and the Arctic Ocean. Among 69982 profiles in 5174 cruises, we could put correction factors of nutrients concentration for 14491 profiles in 268 cruises for nitrate, 18378 profiles in 412 cruises for phosphate and 15825 profiles in 268 cruises for silicate. Global Nutrients Dataset 2010, GND10, is newly created as 0.5 deg. [U+F0B4] 0.5 deg. and 50 m interval of 138 levels gridded dataset based on corrected nutrients profiles described above. One feature of GND10 is that nitrate vs. phosphate ratio in deep waters in WOA dataset showed a peak at 14.6 while nitrate vs. phosphate ratio in GND10 showed a peak at 14.3 and kurtosis of frequency distribution of nitrate vs. phosphate ratio is larger in GND10 dataset rather than that in WOA dataset. A reason of larger kurtosis of distribution of nitrate vs. phosphate ratio might be that comparability of nitrate and phosphate concentration data was improved. Newly created GND10 can provide more realistic distribution of nutrients in the world ocean because comparability of nutrients concentration in GND10 is improved based on RMNS. The GND10 would be useful to study changes in the distribution of concentrations of nutrients in the world ocean and also useful as new initial conditions for modelers who studies global changes. Carbonate system data and oxygen data will be merged with factor corrected nutrients data to study coupling of carbonate system and nutrients cycles, too.Poster abstract EGU2013-3742-1, European Geosciences Union (EGU) General Assembly 2013 (7?12 April, 2013, Vienna, Austria

    Peritoneal keratin granuloma associated with endometrioid adenocarcinoma of the uterine corpus

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    We present a 69-year-old woman with a chief complaint of postmenopausal bleeding. She was diagnosed as having an endometrioid adenocarcinoma by biopsy, and underwent a total abdominal hysterectomy. At the time of surgery, granulation tissue-like nodules were found on the peritoneal serosa of the uterus. In the intraoperative cytology of peritoneal washing, atypical cells were noted. The intraoperative frozen section of the peritoneal nodule revealed granulation tissue with proliferating mesothelial cells. Microscopic examination of the permanent section showed keratin granulomas without viable adenocarcinoma cells on the serosal surface of the ovaries, fallopian tubes and broad ligaments. Postoperative chemotherapy was administered. She has been alive with no evidence of recurrence for 6 months postoperatively. It should be noted that the prognosis of cases in peritoneal keratin granuloma without viable cancer cells is favorable, and that the histological examination is essential for its diagnosis

    Significant Correlation between Chromosomal Aberration and Nuclear Morphology in Urothelial Carcinoma

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    We aimed to identify whether there is any correlation between chromosomal/genetic changes, nuclear morphology and the histological grade of urothelial carcinomas of the urinary bladder. Morphometry and multicolour fluorescence in situ hybridisation (FISH) techniques were applied to 250 cells in five low-grade cases and 350 cells in seven high-grade cases of urothelial carcinoma. Compared with low-grade carcinomas, most high-grade cases showed larger and more variable nuclear size, more frequent polysomy of centromere enumeration probes (CEPs) 3, 7 and 17, and the loss of the 9p21 locus. The number of CEP signals in cells was increased as the nuclear area of the cells became larger. Cells with gains in two or more types of CEP had significantly larger nuclei than cells with normal FISH signal patterns. In conclusion, the present study indicates that there was a correlation between nuclear morphology and chromosomal/genetic changes which were related to histological grading. Thus, we show that differences in the chromosomal/genetic aberrations present in low- and high-grade tumours can affect not only nuclear morphology but also the histopathological and clinical behaviour of urothelial carcinomas

    Amphotericin B assembles into seven-molecule ion channels: An NMR and molecular dynamics study

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    Amphotericin B, an antifungal drug with a long history of use, forms fungicidal ion-permeable channels across cell membranes. Using solid-state nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we experimentally elucidated the three-dimensional structure of the molecular assemblies formed by this drug in membranes in the presence of the fungal sterol ergosterol. A stable assembly consisting of seven drug molecules was observed to form an ion conductive channel. The structure is somewhat similar to the upper half of the barrel-stave model proposed in the 1970s but substantially different in the number of molecules and in their arrangement. The present structure explains many previous findings, including structure-activity relationships of the drug, which will be useful for improving drug efficacy and reducing adverse effects

    Protocol for a Randomized, Crossover Trial : ISCHIA study

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    Objective: Intermittent-scanning continuous glucose monitoring (isCGM) is widely used in type 1 diabetes (T1D) patients; however, the education required to prevent hypoglycemia by using isCGM is not established. This study examines the combined effect of isCGM device usage and the education to reduce the time in hypoglycemia in comparison to conventional self-monitoring of blood glucose (SMBG). Methods: The Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study), a randomized, crossover trial, enrolls 104 T1D patients (age, 20-74 years) with T1D. Participants are randomized to use isCGM combined with structured education (Intervention period) or SMBG (Control period) for 84 days, followed by the other for a further 84 days. During the Intervention period, participants have access to the sensor glucose levels and trend arrow of the device. During the Control period, participants conduct SMBG at least three times a day, and retrospective CGM is used to record the blinded sensor glucose levels. The primary endpoint is the decrease of time in hypoglycemia ( < 70 mg/dL) per day (hour/day) during the Intervention period compared with the Control period. The secondary endpoints include other indices of glycemic control, glycoalbumin, accuracy of isCGM, diabetes-related quality of life (QOL), adherence, and cost-effectiveness. The study protocol has received Certified Review Board (CRB) approval from National Hospital Organization Osaka National Hospital (N2018002, February 14, 2019). This study is carried out in accordance with the Declaration of Helsinki and the Clinical Trials Act. The findings will be published in peer-reviewed journals. Conclusion: The ISCHIA study will contribute to the standardization of patient education regarding the prevention of hypoglycemia by using isCGM

    Roles of Protease-Activated Receptor-2 in Atherogenesis

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    Background: The coagulation system is closely linked with vascular inflammation, although the underlying mechanisms are still obscure. Recent studies show that protease-activated receptor (PAR)-2, a major receptor of activated factor X (FXa), are expressed in both vascular cells and leukocytes, suggesting that PAR-2 may contribute to the pathogenesis of inflammatory diseases. Here we investigated the role of PAR-2 in vascular inflammation and atherogenesis. Methods: We generated apolipoprotein E-deficient (ApoE-/-) mice lacking systemic PAR-2 expression (PAR-2-/-ApoE-/-). ApoE-/- mice which lack or express PAR-2 only in bone-marrow (BM) cells were also generated by BM transplantation. Atherosclerotic lesions were investigated after 20 weeks on a western-type diet (WTD) by histological analyses, quantitative RT-PCR, and western blotting. In vitro experiments using BM-derived macrophages were performed to confirm pro-inflammatory roles of PAR-2. The association between plasma FXa level and the severity of coronary atherosclerosis was also examined in humans who underwent coronary intervention. Results: PAR-2-/-ApoE-/- mice showed reduced atherosclerotic lesions in the aortic arch (P<0.05) along with features of stabilized atherosclerotic plaques such as less lipid deposition (P<0.05), collagen loss (P<0.01), macrophage accumulation (P<0.05), and inflammatory molecule expression (P<0.05) compared with ApoE-/- mice. Systemic PAR2 deletion in ApoE-/- mice significantly decreased the expression of inflammatory molecules in the aorta. The results of BM transplantation experiments demonstrated that PAR-2 in hematopoietic cells contributed to atherogenesis in ApoE-/- mice. PAR-2 deletion did not alter metabolic parameters. In vitro experiments demonstrated that FXa or a specific peptide agonist of PAR-2 significantly increased expression of inflammatory molecules and lipid uptake in BM-derived macrophages from wild-type mice compared with those from PAR-2-deficient mice. Activation of NF-κB signaling was involved in PAR-2-associated vascular inflammation and macrophage activation. In humans who underwent coronary intervention, plasma FXa level independently correlated with the severity of coronary atherosclerosis as determined by Gensini score (P<0.05) and plaque volume (P<0.01). Conclusions: PAR-2 signaling activates macrophages and promotes vascular inflammation, increasing atherosclerosis in ApoE-/- mice. This signaling pathway may also participate in atherogenesis in humans
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