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      • Serum Concentrations of Leptin and Adiponectin in Dogs with Myxomatous Mitral Valve Disease

        Kim, H.&#x2010,S.,Kang, J.&#x2010,H.,Jeung, E.&#x2010,B.,Yang, M.&#x2010,P. John Wiley and Sons Inc. 2016 Journal of veterinary internal medicine Vol.30 No.5

        <P><B>Background</B></P><P>The concentrations of circulating adipokines in dogs with myxomatous mitral valve disease (MMVD) have not been investigated in detail.</P><P><B>Objectives</B></P><P>To determine whether serum concentrations of adipokines differ between healthy dogs and dogs with MMVD and whether circulating concentrations depend on the severity of heart failure resulting from MMVD.</P><P><B>Animals</B></P><P>In the preliminary study, 30 healthy dogs and 17 client‐owned dogs with MMVD, and in the subsequent study, 30 healthy dogs and 46 client‐owned dogs with MMVD.</P><P><B>Methods</B></P><P>Prospective case‐controlled observational study. In the preliminary study, serum concentrations of leptin, adiponectin, resistin, visfatin, interleukin (IL)‐1β, IL‐6, IL‐10, IL‐18, and tumor necrosis factor‐α were measured. In the subsequent study, MMVD dogs were divided into three groups according to the International Small Animal Cardiac Health Council (ISACHC) classification, and serum concentrations of leptin and adiponectin were measured.</P><P><B>Results</B></P><P>In the preliminary study, serum leptin and adiponectin concentrations differed significantly between dogs with MMVD and healthy dogs. Serum leptin (<I>P</I> = .0013) concentrations were significantly higher in dogs with MMVD than in healthy dogs, whereas adiponectin (<I>P</I> = .0009) concentrations were significantly lower in dogs with MMVD. However, we observed no significant differences in the other variables. In the subsequent study, dogs classified as ISACHC class 3 had higher serum concentrations of leptin (<I>P</I> = .0022) than healthy dogs but ISACHC class 1 or 2 dogs did not. Serum adiponectin concentrations were significantly lower in ISACHC class 1 (<I>P</I> < .0001) dogs than in healthy dogs, whereas adiponectin concentrations in ISACHC class 3 dogs were significantly higher than in ISACHC class 1 dogs (<I>P</I> = .0081).</P><P><B>Conclusions and Clinical Importance</B></P><P>Circulating concentrations of leptin and adiponectin might be altered in dogs with MMVD.</P>

      • Association of Obesity with Serum Leptin, Adiponectin, and Serotonin and Gut Microflora in Beagle Dogs

        Park, H.&#x2010,J.,Lee, S.&#x2010,E.,Kim, H.&#x2010,B.,Isaacson, R.E.,Seo, K.&#x2010,W.,Song, K.&#x2010,H. John Wiley and Sons Inc. 2015 Journal of veterinary internal medicine Vol.29 No.1

        <P><B>Background</B></P><P>Serotonin (5‐hydroxytryptamine, 5HT) is involved in hypothalamic regulation of energy consumption. Also, the gut microbiome can influence neuronal signaling to the brain through vagal afferent neurons. Therefore, serotonin concentrations in the central nervous system and the composition of the microbiota can be related to obesity.</P><P><B>Objective</B></P><P>To examine adipokine, and, serotonin concentrations, and the gut microbiota in lean dogs and dogs with experimentally induced obesity.</P><P><B>Animals</B></P><P>Fourteen healthy Beagle dogs were used in this study.</P><P><B>Methods</B></P><P>Seven Beagle dogs in the obese group were fed commercial food ad libitum, over a period of 6 months to increase their weight and seven Beagle dogs in lean group were fed a restricted amount of the same diet to maintain optimal body condition over a period of 6 months. Peripheral leptin, adiponectin, 5HT, and cerebrospinal fluid (CSF‐5HT) levels were measured by ELISA. Fecal samples were collected in lean and obese groups 6 months after obesity was induced. Targeted pyrosequencing of the 16S rRNA gene was performed using a Genome Sequencer FLX plus system.</P><P><B>Results</B></P><P>Leptin concentrations were higher in the obese group (1.98 ± 1.00) compared to those of the lean group (1.12 ± 0.07, <I>P</I> = .025). Adiponectin and 5‐hydroytryptamine of cerebrospinal fluid (CSF‐5HT) concentrations were higher in the lean group (27.1 ± 7.28) than in the obese group (14.4 ± 5.40, <I>P</I> = .018). Analysis of the microbiome revealed that the diversity of the microbial community was lower in the obese group. Microbes from the phylum Firmicutes (85%) were predominant group in the gut microbiota of lean dogs. However, bacteria from the phylum Proteobacteria (76%) were the predominant group in the gut microbiota of dogs in the obese group.</P><P><B>Conclusions and Clinical Importance</B></P><P>Decreased 5HT levels in obese group might increase the risk of obesity because of increased appetite. Microflora enriched with gram‐negative might be related with chronic inflammation status in obese dogs.</P>

      • Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis

        Yu, K&#x2010,H.,Hong, K&#x2010,S.,Lee, B&#x2010,C.,Oh, M&#x2010,S.,Cho, Y&#x2010,J.,Koo, J&#x2010,S.,Park, J&#x2010,M.,Bae, H&#x2010,J.,Han, M&#x2010,K.,Ju, Y&#x2010,S.,Kang, D&#x2010,W.,Appelros, P. Blackwell Publishing Ltd 2011 Acta neurologica Scandinavica Vol.123 No.5

        <P>Yu K‐H, Hong K‐S, Lee B‐C, Oh M‐S, Cho Y‐J, Koo J‐S, Park J‐M, Bae H‐J, Han M‐K, Ju Y‐S, Kang D‐W, Appelros P, Norrving B, Terent A. Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis. 
Acta Neurol Scand: 2011: 123: 325–331. 
© 2010 John Wiley & Sons A/S.</P><P><B>Background – </B> It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case‐fatality between two PSM cohorts of Sweden and Korea.</P><P><B>Methods – </B> Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one‐to‐one matching based on propensity scores of each patient.</P><P><B>Results – </B> After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90‐day case‐fatality was identical 6.2% (HR 0.997, 95%CI 0.905–1.099) in Sweden and Korea.</P><P><B>Conclusions – </B> No difference is found in the 90‐day case‐fatality in propensity score‐matched Swedish and Korean patients with ischemic stroke.</P>

      • MicroRNA signatures associated with immortalization of EBV‐transformed lymphoblastoid cell lines and their clinical traits

        Lee, J.&#x2010,E.,Hong, E.&#x2010,J.,Nam, H.&#x2010,Y.,Kim, J.&#x2010,W.,Han, B.&#x2010,G.,Jeon, J.&#x2010,P. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.1

        <P><B>Abstract</B></P><P><B>Objective: </B> MicroRNAs (miRNAs) are negative regulators of gene expression that play important roles in cell processes such as proliferation, development and differentiation. Recently, it has been reported that miRNAs are related to development of carcinogenesis. The aim of this study was to identify miRNAs associated with terminal immortalization of Epstein–Barr virus (EBV)‐transformed lymphoblastoid cell line (LCL) and associated clinical traits.</P><P><B>Material and Methods: </B> Hence, we performed miRNA microarray approach with early‐ (p6) and late‐passage (p161) LCLs.</P><P><B>Results and Conclusion: </B> Microarray data showed that nine miRNAs (miR‐20b*, miR‐28‐5p, miR‐99a, miR‐125b, miR‐151‐3p, miR‐151:9.1, miR‐216a, miR‐223* and miR‐1296) were differentially expressed in most LCLs during long‐term culture. In particular, miR‐125b was up‐regulated in all the tested late‐passage LCLs. miR‐99a, miR‐125b, miR‐216a and miR‐1296 were putative negative regulators of <I>RASGRP3</I>, <I>GPR160</I>, <I>PRKCH</I> and <I>XAF1</I>, respectively, which were found to be differentially expressed in LCLs during long‐term culture in a previous study. Linear regression analysis showed that miR‐200a and miR‐296‐3p correlated with triglyceride and HbA1C levels, respectively, suggesting that miRNA signatures of LCLs could provide information on the donor’s health. In conclusion, our study suggests that expression changes of specific miRNAs may be required for terminal immortalization of LCLs. Thus, differentially expressed miRNAs would be a potential marker for completion of cell immortalization during EBV‐mediated tumorigenesis.</P>

      • Acute necrotic stomatitis (noma) associated with methicillin‐resistant <i>Staphylococcus aureus</i> infection in a newly acquired rhesus macaque (<i>Macaca mulatta</i>)

        Lee, J.&#x2010,I.,Kim, K.&#x2010,S.,Oh, B.&#x2010,C.,Kim, N.&#x2010,A.,Kim, I.&#x2010,H.,Park, C.&#x2010,G.,Kim, S.&#x2010,J. Blackwell Publishing Ltd 2011 Journal of medical primatology Vol.40 No.3

        <P><B>Abstract</B></P><P><B>Backgroud </B> A newly acquired rhesus macaque was suffering from rapid destruction of the left cheek caused by necrotizing stomatitis.</P><P><B>Methods </B> To restore reconstructive surgery and intensive care with antibiotics, wound protection, wound healing agents, and debridement were applied.</P><P><B>Results </B> <I>Staphylococcus aureus</I> and <I>Enterococcus faecalis</I> were isolated from the culture of the lesion, and the antibiotic susceptibility test revealed methicillin‐resistant <I>Staphylococcus aureus</I> infection. Vancomycin and ampicillin‐sulbactam effectively treated the bacterial infections, and reconstructive surgery was performed once the infection was cleared. Topical application of recombinant human epidermal growth factor (rhEGF) was useful to treat exposed wound of the noma lesion.</P><P><B>Conclusions </B> Simian noma associated with methicillin‐resistant <I>Staphylococcus aureus</I> (MRSA) had not previously been reported in non‐human primates. Although noma associated with MRSA is hard to cure because of its rapid and destructive progress, the aggressive therapy used in this study led to the successful resolution of an acute necrotic stomatitis lesion in a rhesus macaque.</P>

      • <i>In vitro</i> inhibitory effects of Wen‐pi‐tang‐Hab‐Wu‐ling‐san on human cytochrome P450 isoforms

        Lee, H. W.,Kim, D. W.,Phapale, P. B.,Lim, M. &#x2010,S.,Park, J.,Seo, J. J.,Park, K. M.,Park, Y. &#x2010,K.,Yoon, Y. &#x2010,R. Blackwell Publishing Ltd 2011 Journal of clinical pharmacy and therapeutics Vol.36 No.4

        <P><B>Summary</B></P><P><B>What is known and Objective: </B> Although Wen‐pi‐tang‐Hab‐Wu‐ling‐san (WHW), an oriental herbal medicine, has been prescribed for the treatment of chronic renal failure (CRF) in Korean clinics, no studies regarding WHW–drug interactions had been reported. The purpose of this study was to evaluate the possibility that WHW inhibits the catalytic activities of major cytochrome P450 (CYP) isoforms.</P><P><B>Methods: </B> The abilities of various WHW extracts to inhibit phenacetin O‐de‐ethylation (CYP1A2), tolbutamide 4‐methylhydroxylation (CYP2C9), omeprazole 4′‐hydroxylation (CYP2C19), dextromethorphan O‐demethylation (CYP2D6), chlorzoxazone 6‐hydroxylation (CYP2E1) and midazolam 1‐hydroxylation (CYP3A4) were assessed using human liver microsomes.</P><P><B>Results and Discussion: </B> WHW extract at concentrations up to 100 μ<SMALL>m</SMALL> showed negligible inhibition of the six CYP isoforms tested (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4), with apparent IC<SUB>50</SUB> values (concentration of the inhibitor causing 50% inhibition of the original enzyme activity) of 817.5, 601.6, 521.7, 310.2, 342.8 and 487.0 μg/mL, respectively.</P><P><B>What is new and Conclusion: </B> Our <I>in vitro</I> findings suggest that WHW extract at concentrations corresponding to a clinically recommended dosage range has no notable inhibitory effects on CYP isoforms. Therefore, we believe that WHW extract may be free of drug–herb interactions when co‐administered with other medicines. However, <I>in vivo</I> human studies are needed to confirm these results.</P>

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        Estimation of the 6‐digit level allele and haplotype frequencies of HLA‐A, ‐B, and ‐C in Koreans using ambiguity‐solving DNA typing

        Jun, J.&#x2010,H.,Hwang, K.,Kim, S.&#x2010,K.,Oh, H.&#x2010,B.,Cho, M.&#x2010,C.,Lee, K.&#x2010,J. Munksgaard 2014 Tissue antigens Vol.84 No.3

        <P><B>Abstract</B></P><P>Because Korean society is fast becoming multi‐ethnic, the determination of ambiguous human leukocyte antigen (HLA) types using HLA allele frequencies is becoming less applicable. In this study, we focused on the development of new technical methods to directly resolve the ambiguities arising from HLA genotyping. One hundred and fifty unrelated healthy Korean adults were included in this study. All alleles from each HLA locus were first divided into 2–4 groups, with each group amplified in a single PCR tube (multi‐group‐specific amplification, MGSA). To resolve phase ambiguities, some allele groups were also amplified separately in small group‐specific amplification (SGSA) tubes. In order to then resolve incomplete sequence ambiguities, primers for MGSA and SGSA were initially designed to cover additional exons. If needed, a heterozygous ambiguity resolving primer (HARP) or sequence specific primer (SSP) was also used. When MGSA and SGSA methods were applied, the rate of phase ambiguity was greatly reduced to an average of 6% (1.3% in HLA‐A, 15.7% in ‐B, and 2.0% in ‐C). Additional HARP and SSP methods could resolve all the phase ambiguities. Using our proposed method, we also detected three alleles that have not been previously reported in Korea, <I>C*04:82</I>, <I>C*07:18</I>, and <I>C*08:22</I>, and report 6‐digit level HLA allele and haplotype frequencies among Koreans. In conclusion, the use of MGSA/SGSA for the initial amplification step is a cost‐effective method facilitating timely and accurate reporting, given the continuing increase in the ethnic diversity of the Korean population. The MGSA described here can be applicable to various populations and thus could be shared by the majority of HLA typing laboratories. However, efforts to solve HLA ambiguity should continue, because SGSA, HARPs and SSPs would be specific to a particular population.</P>

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        Physciosporin suppresses the proliferation, motility and tumourigenesis of colorectal cancer cells

        Ta&#x15f,, &#x130,sa,Han, Jin,Park, So-Yeon,Yang, Yi,Zhou, Rui,Gamage, Chathurika D.B.,Van Nguyen, Tru,Lee, Ji-Yoon,Choi, Yong Jae,Yu, Young Hyun,Moon, Kyung-Sub,Kim, Kyung Keun,Ha, Hyung-Ho,Kim, Sang Elsevier 2019 Phytomedicine Vol.56 No.-

        <P><B>Abstract</B></P> <P><B>Background</B></P> <P>Lichens, which represent symbiotic associations of fungi and algae, are potential sources of numerous natural products. Physciosporin (PHY) is a potent secondary metabolite found in lichens and was recently reported to inhibit the motility of lung cancer cells via novel mechanisms.</P> <P><B>Purpose</B></P> <P>The present study investigated the anticancer potential of PHY on colorectal cancer (CRC) cells.</P> <P><B>Methods</B></P> <P>PHY was isolated from lichen extract by preparative TLC. The effect of PHY on cell viability, motility and tumourigenicity was elucidated by MTT assay, hoechst staining, flow cytometric analysis, transwell invasion and migration assay, soft agar colony formation assay, Western blotting, qRT-PCR and PCR array <I>in vitro</I> as well as tumorigenicity study <I>in vivo</I>.</P> <P><B>Results</B></P> <P>PHY decreased the viability of various CRC cell lines (Caco2, CT26, DLD1, HCT116 and SW620). Moreover, PHY elicited cytotoxic effects by inducing apoptosis at toxic concentrations. At non-toxic concentrations, PHY dose-dependently suppressed the invasion, migration and colony formation of CRC cells. PHY inhibited the motility of CRC cells by suppressing epithelial-mesenchymal transition and downregulating actin-based motility markers. In addition, PHY downregulated β-catenin and its downstream target genes cyclin-D1 and c-Myc. Moreover, PHY modulated KAI1 C-terminal-interacting tetraspanin and KAI1 expression, and downregulated the downstream transcription factors c-jun and c-fos. Finally, PHY administration showed considerable bioavailability and effectively decreased the growth of CRC xenografts in mice without causing toxicity.</P> <P><B>Conclusion</B></P> <P>PHY suppresses the growth and motility of CRC cells via novel mechanisms.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • Surface‐initiated atom‐transfer radical polymerization of 3‐<i>O</i>‐methacryloyl‐1,2:5,6‐di‐ <i>O</i>‐isopropylidene‐α‐ <small>D</small>‐glucofuranoside onto gold surface

        Yoon, Kuk Ro,Ramaraj, B.,Lee, Seungho,Yu, Jong&#x2010,Sung,Choi, Insung S. Wiley Subscription Services, Inc., A Wiley Company 2009 Journal of biomedical materials research. Part A Vol.a88 No.3

        <P><B>Abstract</B></P><P>A sugar‐containing polymer was grown on gold surface by surface‐initiated atom‐transfer radical polymerization (SI‐ATRP) of methacrylate monomer, 3‐<I>O</I>‐methacryloyl‐1,2:5,6‐di‐<I>O</I>‐isopropylidene‐α‐<SMALL>D</SMALL>‐glucofuranoside (MAIpGIc), using 1,4,8,11‐tetraaza‐1,4,8,11‐tetramethylcyclotetradecane (Me<SUB>4</SUB>Cyclam) as ligand, 2‐bromopropionyl moiety attached on the gold surface as initiator, and Copper(I) bromide as catalyst, respectively, in tetrahydrofuran (THF) medium. The resultant sugar film was characterized by polarized infrared external reflectance spectroscopy (PIERS), X‐ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), field emission scanning electron microscopy (FE‐SEM), ellipsometry, and contact angle goniometry. The IR peaks characteristics of poly(3‐<I>O</I>‐methacryloyl‐α,β‐<SMALL>D</SMALL>‐glucopyranoside) (PMAGlc), broad OH stretch at ∼3400 cm<SUP>−1</SUP>, and CO ester stretch at ∼1748 cm<SUP>−1</SUP> observed in PIERS spectra demonstrate the formation of PMAGlc on the gold surface. The AFM and SEM images show the polymer growth away from the gold surface without visible domain boundaries, and it further confirms the formation of sugar coating. The method described in the article would be beneficial in many areas, such as pathogen detection and biosensors, considering the biological importance of carbohydrate polymers. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009</P>

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        High prevalence of unrecognized cerebral infarcts in first‐ever stroke patients with cardioembolic sources

        Cho, A.&#x2010,H.,Kwon, S. U.,Kim, T.&#x2010,W.,Lee, S.&#x2010,J.,Shon, Y.&#x2010,M.,Kim, B. S.,Yang, D. W. Blackwell Publishing Ltd 2009 European Journal of Neurology Vol.16 No.7

        <P><B>Background: </B> With magnetic resonance imaging (MRI) analysis, we investigated the prevalence, clinical significance, and factors related to the presence of unrecognized cerebral infarcts in patients with first‐ever ischaemic stroke.</P><P><B>Methods: </B> We consecutively included patients who were admitted with first‐ever stroke. Unrecognized cerebral infarct was defined as an ischaemic infarction or primary intracerebral hemorrhage on MRI irrelevant to the index stroke, without acute lesions on diffusion‐weighted image.</P><P><B>Results: </B> Of the total 203 patients, 78 (39.4%) patients were observed as having unrecognized cerebral infarct. Patients with high‐risk cardioembolic sources (e.g., atrial fibrillation) more frequently had unrecognized stroke than those without (<I>P</I> = 0.008, 21/36 [58.3%] vs. 57/167 [34.1%]). On univariate analysis, male sex (<I>P</I> = 0.027) and cardioembolic source (<I>P</I> = 0.008) were associated with the presence of unrecognized cerebral infarcts. After adjustment for gender, age and risk factors, the presence of cardioembolic sources independently increased the risk of unrecognized cerebral infarct (<I>P</I> = 0.002, odds ratio 3.56, 95% confidence interval 1.58–8.02). Regarding clinical outcome at 3 months, the presence of unrecognized cerebral infarct was not associated with the poor clinical outcome.</P><P><B>Conclusion: </B> In our study, the presence of cardioembolic sources was an independent risk factor for the unrecognized cerebral infarct in patients with first‐ever stroke.</P>

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