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      • 高速液體크로마토그라프法에 의한 錠劑 중 Strychnine Nitrate 및 Yohimbine Hydrochloride 의 同時定量

        李允中,曺正吉,李東宣,丁海秀 成均館大學校 科學技術硏究所 1987 論文集 Vol.38 No.1

        A simple, rapid extraction and simultaneous determination for yohimbine hydrochloride and strychnine nitrate in tablets, using high performance liquid chromatography with a reverse-phase solvent system, is described. Samples were extracted with 50% methanol by sonication. The extracts were filtrated and applied to HPLC. HPLCs of yohimbine hydrochloride and strychnine nitrate were carried out on μ-Bondapak C_18 Radial-pak cartridge(8mm i.d. x 10 cm) and CH_3CN/H_2O/CH_3COOH=20/78/2 for the solvent system. Recoveries from model preparations were more than 98%. This method was considered to be useful for the determination of yohimbine hydrochloride and strychnine nitrate in tablets at the same time.

      • SCOPUSKCI등재

        Cytotoxic Effects on HL-60 Cells of Myosin Light Chain Kinase Inhibitor ML-7 Alone and in Combination with Flavonoids

        Lee, Joong-Won,Kim, Yang-Jee,Choi, Young-Joo,Woo, Hae-Dong,Kim, Gye-Eun,Ha, Tae-Kyung,Lee, Young-Hyun,Chung, Hai-Won Korean Society of ToxicologyKorea Environmental Mu 2009 Toxicological Research Vol.26 No.4

        Uncontrolled cell growth and increased cell proliferation are major features of cancer that are dependent on the stable structure and dynamics of the cytoskeleton. Since stable cytoskeleton structure and dynamics are partly regulated by myosin light chain kinase (MLCK), many current studies focused on MLCK inhibition as a chemotherapeutic target. As a potent and selective MLCK inhibitor, ML-7 [1-(5-iodonaphthalene-1-sulfonyl)-1 H-hexahydro-1,4-diazapine hydrochloride] is a promising candidate for an anticancer agent, which would induce apoptosis as well as prevents invasion and metastasis in certain types of cancer cells. This study assessed cytotoxic effects of ML-7 against HL-60 cells and therapeutic efficacy of ML-7 as a potential antileukemia agent. Trypan-blue exclusion assays showed dose- and time- dependent decreases in ML-7 treated HL-60 cells (p<0.05). Comet assays revealed a significant increase in DNA damage in HL-60 cells after treatment with $40{\mu}M$ ML-7 for 2h. Sub-G1 fractions, analyzed by flow cytometry increased in a dose-dependent manner, suggesting that ML-7 can induce apoptotic cell death in HL-60 cells. ML-7 was selectively cytotoxic towards HL-60 cells; not affecting normal human lymphocytes. That selective effect makes it a promising potential anti-leukemia agent. In addition, anticancer efficacy of ML-7 in combination with flavonoids (genistein or quercetin) or anticancer drugs (cisplatin or Ara-C) against HL-60 cells was assessed. Combination of ML-7 with flavonoids increased the anti-cancer effect of ML-7 to a greater extent than combination with the anticancer drugs. This implies that ML-7 in combination with flavonoids could increase the efficacy of anticancer treatment, while avoiding side effects cansed by conventional anticancer drug-containing combination chemotherapy.

      • SCISCIESCOPUS

        Association of urinary phthalate metabolites and phenolics with adipokines and insulin resistance related markers among women of reproductive age

        Lee, Inae,Kim, Sunmi,Park, Suhyeon,Mok, Sori,Jeong, Yunsun,Moon, Hyo-Bang,Lee, Jangwoo,Kim, Sungkyoon,Kim, Hai-Joong,Choi, Gyuyeon,Choi, Sooran,Kim, Su Young,Lee, Aram,Park, Jeongim,Choi, Kyungho Elsevier BV 2019 Science of the Total Environment Vol.688 No.-

        <P><B>Abstract</B></P> <P>Chemicals such as phthalates and phenolics have been associated with metabolic markers in humans. However, most studies have only looked at a limited number of chemicals, and little is known about their potential effects on adipokines in humans. In the present study, the associations between dozens of urinary chemicals, including phthalate metabolites and phenolics, and markers related to insulin resistance as well as major adipokines, were assessed among the women of reproductive age (<I>n</I> = 459, between 20 and 48 years of age) recruited from major cities in Korea between 2015 and 2016. Adipokines such as adiponectin and leptin, and insulin resistance related markers such as glucose and insulin, were analyzed in serum. Associations between urinary chemicals and the adipokines or insulin resistance related markers were assessed in two steps. First, ordinary least squares (OLS) regression was used to assess the association of each urinary chemical with the adipokines or insulin resistance related markers (single-pollutant model). Second, several chemicals were selected using elastic net regression and were subsequently analyzed with OLS regression model (multi-pollutant model), considering simultaneous exposure to multiple chemicals. In both single- and multi-pollutant models, several urinary chemicals consistently showed significant associations with adipokines or the insulin resistance related markers. The sum of di-(2-ethylhexyl) phthalate metabolites (ΣDEHPm) and ethyl paraben (EtP) were associated with increased serum adiponectin levels. Urinary ΣDEHPm levels also showed positive associations with fasting glucose. Moreover, urinary mono-methyl phthalate (MMP), mono-isobutyl phthalate (MiBP), and bisphenol S (BPS) levels showed positive associations with the homeostasis model assessment for insulin resistance (HOMA-IR). Interestingly, urinary propyl paraben (PrP) levels showed a negative association with HOMA-IR, in both models. Our observations show that among many consumer chemicals, phthalates may affect serum adipokines, and thus glucose, and insulin resistance in adult females. Further confirmation is warranted in other populations.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Urinary chemicals and metabolism related markers were measured in women of reproductive age. </LI> <LI> Multiple chemicals were considered in statistical models for adipokines and insulin resistance. </LI> <LI> Sum of DEHP metabolites and EtP were positively associated with serum adiponectin levels. </LI> <LI> Sum of DEHP metabolites was significantly associated with increased fasting glucose. </LI> <LI> MiBP was significantly associated with for increased HOMA-IR. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • SCISCIESCOPUS

        Genotoxic effects of 3 T magnetic resonance imaging in cultured human lymphocytes

        Lee, Joong Won,Kim, Myeong Seong,Kim, Yang Jee,Choi, Young Joo,Lee, Younghyun,Chung, Hai Won Wiley Subscription Services, Inc., A Wiley Company 2011 Bioelectromagnetics Vol.32 No.7

        <P><B>Abstract</B></P><P>The clinical and preclinical use of high‐field intensity (HF, 3 T and above) magnetic resonance imaging (MRI) scanners have significantly increased in the past few years. However, potential health risks are implied in the MRI and especially HF MRI environment due to high‐static magnetic fields, fast gradient magnetic fields, and strong radiofrequency electromagnetic fields. In this study, the genotoxic potential of 3 T clinical MRI scans in cultured human lymphocytes in vitro was investigated by analyzing chromosome aberrations (CA), micronuclei (MN), and single‐cell gel electrophoresis. Human lymphocytes were exposed to electromagnetic fields generated during MRI scanning (clinical routine brain examination protocols: three‐channel head coil) for 22, 45, 67, and 89 min. We observed a significant increase in the frequency of single‐strand DNA breaks following exposure to a 3 T MRI. In addition, the frequency of both CAs and MN in exposed cells increased in a time‐dependent manner. The frequencies of MN in lymphocytes exposed to complex electromagnetic fields for 0, 22, 45, 67, and 89 min were 9.67, 11.67, 14.67, 18.00, and 20.33 per 1000 cells, respectively. Similarly, the frequencies of CAs in lymphocytes exposed for 0, 45, 67, and 89 min were 1.33, 2.33, 3.67, and 4.67 per 200 cells, respectively. These results suggest that exposure to 3 T MRI induces genotoxic effects in human lymphocytes. Bioelectromagnetics 32:535–542, 2011. © 2011 Wiley‐Liss, Inc.</P>

      • Radiation-induced changes in DNA methylation and their relationship to chromosome aberrations in nuclear power plant workers

        Lee, Younghyun,Kim, Yang Jee,Choi, Young Joo,Lee, Joong Won,Lee, Sunyeong,Cho, Yoon Hee,Chung, Hai Won Informa Healthcare 2015 International Journal of Radiation Biology Vol.91 No.2

        <P><I>Purpose</I>: We investigated the association between occupational radiation exposure and DNA methylation changes in nuclear power plant workers. We also evaluated whether radiation- induced DNA methylation alterations are associated with chromosome aberrations.</P><P><I>Materials and methods</I>: The study population included 170 radiation-exposed workers and 30 controls. We measured global, long interspersed nuclear element-1 (LINE-1), and satellite 2 methylation levels in blood leukocyte DNA. The analysis of chromosome aberrations was performed on peripheral lymphocytes.</P><P><I>Results</I>: Global DNA methylation levels were lower in radiation-exposed workers than in controls. The methylation levels were negatively associated with the recent 1.5-year radiation dose in a multiple linear regression model (β = − 0.0088, <I>p</I> ≤ 0.001); the levels increased proportionally with the total cumulative dose in radiation-exposed workers. LINE-1 methylation levels were higher in radiation-exposed workers than in controls and were significantly associated with the total cumulative radiation dose in a multiple linear regression model (β = − 0.031, <I>p</I> = 0.035). Global DNA methylation levels were also correlated with chromosome aberrations among workers. Workers with low global methylation levels had a higher frequency of chromosome aberrations than did subjects with high global methylation levels.</P><P><I>Conclusion</I>: Occupational exposure to low-dose radiation could affect DNA methylation levels, and the radiation-induced DNA methylation alterations may be associated with chromosome aberrations.</P>

      • SCOPUSKCI등재

        Kinetic Isotope Effects in the Nucleophilic Substitution Reactions of Benzyl- and 1-Phenylethyl -benzenesulfonates with Deuterated Aniline Nucleophiles

        Lee, Ik-Choon,Koh, Han-Joong,Lee, Bon-Su,Lee, Hai-Whang,Choi, Jae-Ho Korean Chemical Society 1990 Bulletin of the Korean Chemical Society Vol.11 No.5

        Primary and secondary ${\alpha}$-deuterium kinetic isotope effects are determined with deuterated aniline nucleophiles in the nucleophilic substitution reactions of benzyl benzenesulfonates and 1-phenylethyl benzenesulfonates in acetonitrile at 30.0^{\circ}C. The $k_H/k_D$ values support our previous conclusions regarding the transition state structures proposed for the two reactions based on the cross-interaction constants ${\rho}_{ij}$; the former is a typical $S_N2$ reaction whereas in the latter the four-center transition state may be involved.

      • Effects of Recombinant Adenovirus-Mediated Uncoupling Protein 2 Overexpression on Endothelial Function and Apoptosis

        Lee, Ki-Up,Lee, In Kyu,Han, Jin,Song, Dae-Kyu,Kim, Yun Mi,Song, Hai Sun,Kim, Hyoun Sik,Lee, Woo Je,Koh, Eun Hee,Song, Kee-Ho,Han, Sung Min,Kim, Min Seon,Park, In-Sun,Park, Joong-Yeol Ovid Technologies Wolters Kluwer -American Heart A 2005 Circulation research Vol.96 No.11

        <P>Increased oxidative stress in vascular cells plays a key role in the development of endothelial dysfunction and atherosclerosis. Uncoupling protein 2 (UCP2) is an important regulator of intracellular reactive oxygen species (ROS) production. This study was undertaken to test the hypothesis that, UCP2 functions as an inhibitor of the atherosclerotic process in endothelial cells. Adenovirus-mediated UCP2 (Ad-UCP2) overexpression led to a significant increase in endothelial nitric oxide synthase (eNOS) and decrease in endothelin-1 mRNA expression in human aortic endothelial cells (HAECs). Moreover, UCP2 inhibited the increase in ROS production and NF-kappaB activation, and apoptosis of HAECs induced by lysophophatidylcholine (LPC) and linoleic acid. LPC and linoleic acid caused mitochondrial calcium accumulation and transient mitochondrial membrane hyperpolarization, which was followed by depolarization. UCP2 overexpression prevented these processes. In isolated rat aorta, Ad-UCP2 infection markedly improved impaired vascular relaxation induced by LPC. The data collectively suggest that UCP2, functions as a physiologic regulator of ROS generation in endothelial cells. Thus, measures to increase UCP2 expression in vascular endothelial cells may aid in preventing the development and progression of atherosclerosis in patients with metabolic syndrome.</P>

      • KCI등재

        Cytotoxic Effects on HL-60 Cells of Myosin Light Chain Kinase Inhibitor ML-7 Alone and in Combination with Flavonoids

        Joong Won Lee,Yang Jee Kim,Young Joo Choi,Hae Dong Woo,Gye Eun Kim,Tae Kyung Ha,Young Hyun Lee,Hai Won Chung 한국독성학회 2009 Toxicological Research Vol.25 No.4

        Uncontrolled cell growth and increased cell proliferation are major features of cancer that are dependent on the stable structure and dynamics of the cytoskeleton. Since stable cytoskeleton structure and dynamics are partly regulated by myosin light chain kinase (MLCK), many current studies focused on MLCK inhibition as a chemotherapeutic target. As a potent and selective MLCK inhibitor, ML-7 [1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazapine hydrochloride] is a promising candidate for an anticancer agent, which would induce apoptosis as well as prevents invasion and metastasis in certain types of cancer cells. This study assessed cytotoxic effects of ML-7 against HL-60 cells and therapeutic efficacy of ML-7 as a potential antileukemia agent. Trypan-blue exclusion assays showed dose- and time- dependent decreases in ML-7 treated HL-60 cells (p < 0.05). Comet assays revealed a significant increase in DNA damage in HL-60 cells after treatment with 40 μM ML-7 for 2 h. Sub-G1 fractions, analyzed by flow cytometry increased in a dose-dependent manner, suggesting that ML-7 can induce apoptotic cell death in HL-60 cells. ML-7 was selectively cytotoxic towards HL-60 cells; not affecting normal human lymphocytes. That selective effect makes it a promising potential anti-leukemia agent. In addition, anticancer efficacy of ML-7 in combination with flavonoids (genistein or quercetin) or anticancer drugs (cisplatin or Ara-C) against HL-60 cells was assessed. Combination of ML-7 with flavonoids increased the anti-cancer effect of ML-7 to a greater extent than combination with the anticancer drugs. This implies that ML-7 in combination with flavonoids could increase the efficacy of anticancer treatment, while avoiding side effects cansed by conventional anticancer drug-containing combination chemotherapy.

      • SCISCIESCOPUS

        Perfluoroalkyl substances (PFASs) in breast milk from Korea: Time-course trends, influencing factors, and infant exposure

        Lee, Sunggyu,Kim, Sunmi,Park, Jeongim,Kim, Hai-Joong,Choi, Gyuyeon,Choi, Sooran,Kim, Sungjoo,Kim, Su Young,Kim, Sungkyoon,Choi, Kyungho,Moon, Hyo-Bang Elsevier 2018 Science of the Total Environment Vol.612 No.-

        <P><B>Abstract</B></P> <P>Breastfeeding is an important exposure pathway to perfluoroalkyl substances (PFASs) for newborn infants. Nevertheless, reports are limited on the occurrence and time-course of PFASs in breast milk, and most studies have focused on the analysis of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). In this study, 16 PFASs were analyzed in breast milk samples (<I>n</I> =293) collected from 128 mothers in Korea during various lactation periods to assess maternal exposure levels, contamination profiles, time-course variations, and infant health risks. The total concentrations of PFASs (ΣPFAS) ranged from 31.7 to 1004 (median: 188) ng/L, which was within the ranges recently reported for Asian and European populations. After a month of nursing, the concentrations of PFOS, PFOA, perfluorononanoic acid (PFNA), and ΣPFAS significantly increased. This could be due to changes in the dietary and behavior patterns of the mothers after the first month of lactation. The concentrations of PFOS and PFOA were significantly correlated with maternal age, body mass index, and parity. Certain types of diet (e.g. consuming snacks and milk) and eating-out frequency were significantly associated with increasing levels of PFAS. Significant correlations and similar time-course trends were found between PFASs and PCBs/DDTs, implying similar exposure sources and biokinetics for these contaminants. The estimated daily intakes of PFOS and PFOA via the consumption of breast milk were below the tolerable daily intakes for infants suggested by the European Food Safety Authority (EFSA).</P> <P><B>Highlights</B></P> <P> <UL> <LI> PFOS, PFOA, PFUnDA, and PFNA were the predominant compounds in breast milk. </LI> <LI> Concentrations of PFASs were significantly correlated with maternal age, BMI, and parity. </LI> <LI> Increased levels of PFASs were found in breast milk after the first month of nursing. </LI> <LI> Snack consumption and frequency of eating-out were significantly associated with increased PFAS levels. </LI> <LI> The infant exposure levels of PFOS and PFOA via breast milk were lower than the TDI. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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