Factors Influencing the Use of English Demonstratives

Yu, Hyewon 고려대학교 언어정보연구소 2018 언어정보 Vol.27 No.-

The purpose of this study is to investigate which factors influence the choice of English demonstratives and to examine Koreans’ use of English demonstratives. Two experiments were conducted in the research – one was to examine which factors decide the degree of focus, the concept used in the theory suggested by Strauss (1992) as one of the criteria of demonstrative choices, and the other was to explore whether Korean students know that the focus of entities as well as distance affects the use of English demonstratives. For both experiments, task-type questionnaires were used and the results were analyzed using chi-square statistics. In Experiment 1, native English speakers and Korean adults who are advanced learners of English participated. The study indicated that both of the groups were influenced most by ownership among the three factors, ownership, meaningfulness, and price. Experiment 2 was carried out subsequently to investigate if the concept of ownership in fact influence Korean high school students’ use of English demonstratives. The results indicated that ownership, the factor which was used as a substitute of focus in this experiment, did not affect high school students’ choices much. These results suggest that they might not be yet aware of the fact that not only distance but also other aspects such as ownership can have an impact on the choice of English demonstratives.

The Effect of Tanespimycin (17-AAG) on Radioiodine Accumulation in Sodium-Iodide Symporter Expressing Cells

Yu, Kyoung Hyun,Youn, Hyewon,Song, Myung Geun,Lee, Dong Soo,Chung, June-Key The Korea Society of Nuclear Medicine 2012 핵의학 분자영상 Vol.46 No.4

Purpose The heat shock protein 90 inhibitor, tanespimycin, is an anticancer agent known to increase iodine accumulation in normal and cancerous thyroid cells. Iodine accumulation is regulated by membrane proteins such as sodium iodide symporter (NIS) and pendrin (PDS), and thus we attempted to characterize the effects of tanespimycin on those genes. Methods Cells were incubated with tanespimycin in order to evaluate $^{125}I$ accumulation and efflux ability. Radioiodine uptake and efflux were measured by a gamma counter and normalized by protein amount. RT-PCR were performed to measure the level of gene expression. Results After tanespimycin treatment, $^{125}I$ uptake was increased by ~2.5-fold in FRTL-5, hNIS-ARO, and hNIS-MDA-MB-231 cells, but no changes were detected in the hNIS-HeLa cells. Tanespimycin significantly reduced the radioiodine efflux rate only in the FRTL-5 cells. In the FRTL-5 and hNIS-ARO cells, PDS mRNA levels were markedly reduced; the only other observed alteration in the levels of NIS mRNA after tanespimycin treatment was an observed increase in the hNIS-ARO cells. Conclusions These results indicate that cellular responses against tanespimycin treatment differed between the normal rat thyroid cells and human cancer cells, and the reduction in the $^{125}I$ efflux rate by tanespimycin in the normal rat thyroid cells might be attributable to reduced PDS gene expression.

Soluble Vascular Endothelial Growth Factor Decoy Receptor FP3 Exerts Potent Antiangiogenic Effects

Yu, De-Chao,Lee, Jung-Sun,Yoo, Ji Young,Shin, Hyewon,Deng, Hongxin,Wei, Yuquan,Yun, Chae-Ok Elsevier 2012 Molecular therapy Vol.20 No.5

DA-6034 Induces [Ca²⁺]i Increase in Epithelial Cells

Yu-Mi Yang,Soonhong Park,HyeWon Ji,Tae-im Kim,Eung Kweon Kim,Kyung Koo Kang,Dong Min Shin 대한생리학회-대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.2

DA-6034, a eupatilin derivative of flavonoid, has shown potent effects on the protection of gastric mucosa and induced the increases in fluid and glycoprotein secretion in human and rat corneal and conjunctival cells, suggesting that it might be considered as a drug for the treatment of dry eye. However, whether DA-6034 induces Ca²⁺ signaling and its underlying mechanism in epithelial cells are not known. In the present study, we investigated the mechanism for actions of DA-6034 in Ca²⁺ signaling pathways of the epithelial cells (conjunctival and corneal cells) from human donor eyes and mouse salivary gland epithelial cells. DA-6034 activated Ca²⁺-activated Cl- channels (CaCCs) and increased intracellular calcium concentrations ([Ca²⁺]i) in primary cultured human conjunctival cells. DA-6034 also increased [Ca²⁺]i in mouse salivary gland cells and human corneal epithelial cells. [Ca²⁺]i increase of DA-6034 was dependent on the Ca²⁺ entry from extracellular and Ca²⁺ release from internal Ca²⁺ stores. Interestingly, these effects of DA-6034 were related to ryanodine receptors (RyRs) but not phospholipase C/inositol 1,4,5-triphosphate (IP₃) pathway and lysosomal Ca²⁺ stores. These results suggest that DA-6034 induces Ca²⁺ signaling via extracellular Ca²⁺ entry and RyRs-sensitive Ca²⁺ release from internal Ca²⁺ stores in epithelial cells.

The effect of salinomycin on ovarian cancer stem-like cells

( Hyewon Chung ),( Yu-hwan Kim ),( Myoung Kwon ),( So-jin Shin ),( Sang-hoon Kwon ),( Soon-do Cha ),( Chi-heum Cho ) 대한산부인과학회 2016 Obstetrics & Gynecology Science Vol.59 No.4

Objective The identification of cancer stem-like cells is a recent development in ovarian cancer. Compared to other cancer cells, cancer stem-like cells present more chemo-resistance and more aggressive characteristics. They play an important role in the recurrence and drug resistance of cancer. Therefore, the target therapy of cancer stem-like cell may become a promising and effective approach for ovarian cancer treatment. It may also help to provide novel diagnostic and therapeutic strategies. Methods The OVCAR3 cell line was cultured under serum-free conditions to produce floating spheres. The CD44+CD117+ cell line was isolated from the human ovarian cancer cell line OVCAR3 by using immune magnetic-activated cell sorting system. The expression of stemness genes such as OCT3/4, NANOG and SOX2 mRNA were determined by reverse transcription polymerase chain reaction. OVCAR3 parental and OVCAR3 CD44+CD117+ cells were grown in different doses of paclitaxel and salinomycin to evaluate the effect of salinomycin. And growth inhibition of OVCAR3 CD44+CD117+ cells by paclitaxel combined with salinomycin was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl-2H-tetrazolium bromide (MTT) assay. Results Tumor spheroids generated from the OVCAR3 cell line are shown to have highly enriched CD44 and CD117 expression. Treatment with a combination of paclitaxel and salinomycin demonstrated growth inhibition of OVCAR3 CD44+CD117+ cells. Conclusion The present study is a detailed investigation on the expression of CD44 and CD117 in cancer stem cells and evaluates their specific tumorigenic characteristics in ovarian cancer. This study also demonstrates significant growth inhibition of cancer stem-like cells by paclitaxel combined with salinomycin. Identification of these cancer stem-like cell markers and growth inhibition effect of salinomycin may be the next step to the development of novel target therapy in ovarian cancer.

관상동맥 질환 판독과 자료 체계와 CT 혈관조영술에서의 경계성 관상동맥 병변

Hyewon Park,Yu-Whan Oh,Ki Yeol Lee,Hwan Seok Yong,Cherry Kim,Sung Ho Hwang 대한영상의학회 2024 대한영상의학회지 Vol.85 No.2

관상동맥 질환은 죽상동맥경화(atherosclerosis)로 인해 혈관의 내강이 좁아지면서 심근허혈 또는 경색까지 유발할 수 있는 질병이다. 이런 관상동맥 질환은 조기에 진단해서 치료하면 그만큼 예후가 좋기에 정확한 진단이 환자 관리에서 매우 중요하다. 전산화단층촬영 혈관조영술(CT angiography; 이하 CTA)은 높은 해상도와 대조도를 통해 혈관의 구조 및 협착 정도를 세밀하게 평가할 수 있는 비침습적 영상 진단법이다. 여러 임상시험들이 관상동맥 질환에 대한 조기 진단과 평가에 있어 관상동맥 CTA의 유용성을 보고하였다. 최근에 관상동맥질환이 의심되는 환자들에 대한 보다 효과적인 처치를 위해 CTA에 기반한 관상동맥 질환 진단 분류 체계인 관상동맥 질환 판독과 자료 체계(coronary artery disease-reporting and data system; 이하 CAD-RADS)가 만들어졌다. 이런 CAD-RADS는 관상동맥 CTA를 기반으로 하지만 CAD-RADS는 CTA 결과만으로 관상동맥의 정확한 상태를 해석하는 것이 어려운경계선 범주를 포함하고 있다. 본 종설은 침습적 관상동맥 조영술 진행 여부를 결정하기에앞서 추가검사가 필요한 경계선상 CAD-RADS범주들의 CTA의 소견과 이들에 대한 대처를논하고자 한다. Coronary artery disease (CAD) narrows vessel lumens at the sites of atherosclerosis, increasing the risk of myocardial ischemia or infarction. Early and accurate diagnosis of CAD is crucial to significantly improve prognosis and management. CT angiography (CTA) is a noninvasive imaging technique that enables assessment of vascular structure and stenosis with high resolution and contrast. Coronary CTA is useful in the diagnosis of CAD. Recently, the CAD-reporting and data system (CAD-RADS), a diagnostic classification system based on coronary CTA, has been developed to improve intervention efficacy in patients suspected of CAD. While the CADRAD is based on CTA, it includes borderline categories where interpreting the coronary artery status solely based on CTA findings may be challenging. This review introduces CTA findings that fall within the CAD-RADS categories that necessitate additional tests to decide to perform invasive coronary angiography and discusses appropriate management strategies.

A pharmacokinetic comparison of two voriconazole formulations and the effect of CYP2C19 polymorphism on their pharmacokinetic profiles

Chung, Hyewon,Lee, Howard,Han, HyeKyung,An, Hyungmi,Lim, Kyoung Soo,Lee, Yong Jin,Cho, Joo-Youn,Yoon, Seo Hyun,Jang, In-Jin,Yu, Kyung-Sang Dove Medical Press 2015 Drug design, development and therapy Vol.9 No.-

<P><B>Purpose</B></P><P>SYP-1018 is a lyophilized polymeric nanoparticle formulation of voriconazole that is under development for intravenous dosing. This study compared the pharmacokinetic and tolerability profiles of SYP-1018 with those of Vfend<SUP>®</SUP>, the marketed formulation of voriconazole. The effect of CYP2C19 polymorphism on the voriconazole pharmacokinetics was also evaluated.</P><P><B>Methods</B></P><P>An open-label, two-treatment, two-period, two-sequence crossover study was conducted in 52 healthy male volunteers, who randomly received a single intravenous infusion of either of the two voriconazole formulations at 200 mg. Blood samples were collected up to 24 hours after drug administration for pharmacokinetic analysis. The plasma concentrations of voriconazole were determined using liquid chromatography with tandem mass spectrometry, and the pharmacokinetic parameters were estimated using a noncompartmental method. CYP2C19 genotype was identified in 51 subjects.</P><P><B>Results</B></P><P>The geometric mean ratio (90% confidence interval) of SYP-1018 to Vfend<SUP>®</SUP> was 0.99 (0.93–1.04) for the maximum plasma concentrations (C<SUB>max</SUB>) and 0.97 (0.92–1.01) for the area under the concentration–time curve (AUC) from dosing to the last quantifiable concentration (AUC<SUB>last</SUB>). Nineteen homozygous extensive metabolizers (EMs, *1/*1), 19 intermediate metabolizers (IMs, *1/*2 or *1/*3), and ten poor metabolizers (PMs, *2/*2, *2/*3, or *3/*3) were identified, and the pharmacokinetic comparability between SYP-1018 and Vfend<SUP>®</SUP> was also noted when analyzed separately by genotype. The systemic exposure to voriconazole was greatest in the PM group, followed by the IM, and then the EM groups. Furthermore, the intrasubject variability for C<SUB>max</SUB> and AUC<SUB>last</SUB> was greater in IMs and PMs than in EMs. No serious adverse event occurred, and both treatments were well tolerated.</P><P><B>Conclusion</B></P><P>SYP-1018 had comparable pharmacokinetic and tolerability profiles to Vfend<SUP>®</SUP> after a single intravenous infusion. CYP2C19 genotype affected not only the pharmacokinetics of voriconazole, but its intrasubject variability. SYP-1018 can be further developed as a clinically effective alternative to Vfend<SUP>®</SUP>.</P>

Pharmacokinetics and effect on the corrected QT interval of single-dose escitalopram in healthy elderly compared with younger adults

Chung, Hyewon,Kim, Anhye,Lim, Kyoung Soo,Park, Sang-In,Yu, Kyung-Sang,Yoon, Seo Hyun,Cho, Joo-Youn,Chung, Jae-Yong Lippincott, Williams and Wilkins 2017 International clinical psychopharmacology Vol.32 No.1

<P>Escitalopram is the (S)-enantiomer of citalopram that has a potential QT prolonging effect. In this study, 12 healthy elderly individuals received a single oral dose of escitalopram (20 mg), and their pharmacokinetics and QT effect data were compared with data from 33 younger adults obtained in a previous study. Serial blood samples for pharmacokinetic analysis were collected and ECG was performed up to 48 h postdose. The elderly and younger adults showed similar pharmacokinetic profiles. The geometric mean ratios (90% confidence interval) of the elderly compared with the younger adults were 1.02 (0.89-1.17) and 1.01 (0.86-1.17) for the maximum plasma concentration and area under the concentration-time curve, respectively. The mean baseline-adjusted QT (dQT) time profiles were similar and the mean values of maximum dQT were not significantly different between the elderly and the younger adults. The linear mixed-effect model indicated a weak but positive relationship between the escitalopram concentration and dQT, with an estimated coefficient of concentration of 0.43-0.54. In conclusion, the pharmacokinetics and QT effect of a single dose of escitalopram observed in the elderly without comorbidities and younger adults were generally similar. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.</P>

The <i>Drosophila</i> homolog of methionine sulfoxide reductase A extends lifespan and increases nuclear localization of FOXO

Chung, Hyewon,Kim, Ae-kyeong,Jung, Sun-Ah,Kim, Si Wouk,Yu, Kweon,Lee, Joon H. Elsevier 2010 FEBS letters Vol.584 No.16

<P><B>Abstract</B></P><P>Methionine sulfoxide reductase A (msrA) was previously found to increase resistance to oxidative stress and longevity in animals. We identified <I>Drosophila</I> msrA (<I>dmsrA</I>), a <I>Drosophila</I> homolog of human <I>msrA</I>, as a downstream effector of forkhead box O (FOXO) signaling in <I>Drosophila</I>, which enhances resistance to oxidative stress and increases survival under stressed conditions. Additionally, overexpression of <I>dmsrA</I> in neurons extended the lifespan of flies. Moreover, overexpression of <I>dmsrA</I> in fat body cells caused FOXO to translocate to the nucleus, implying that this possible positive feedback loop between <I>dmsrA</I> and FOXO could potentiate the antioxidant activity of <I>dmsrA</I> and increase the lifespan in <I>Drosophila</I>.</P>

DA-6034 Induces $[Ca^{2+}]_i$ Increase in Epithelial Cells

Yang, Yu-Mi,Park, Soonhong,Ji, HyeWon,Kim, Tae-Im,Kim, Eung Kweon,Kang, Kyung Koo,Shin, Dong Min The Korean Society of Pharmacology 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.2

DA-6034, a eupatilin derivative of flavonoid, has shown potent effects on the protection of gastric mucosa and induced the increases in fluid and glycoprotein secretion in human and rat corneal and conjunctival cells, suggesting that it might be considered as a drug for the treatment of dry eye. However, whether DA-6034 induces $Ca^{2+}$ signaling and its underlying mechanism in epithelial cells are not known. In the present study, we investigated the mechanism for actions of DA-6034 in $Ca^{2+}$ signaling pathways of the epithelial cells (conjunctival and corneal cells) from human donor eyes and mouse salivary gland epithelial cells. DA-6034 activated $Ca^{2+}$-activated $Cl^-$ channels (CaCCs) and increased intracellular calcium concentrations ($[Ca^{2+}]_i$) in primary cultured human conjunctival cells. DA-6034 also increased $[Ca^{2+}]_i$ in mouse salivary gland cells and human corneal epithelial cells. $[Ca^{2+}]_i$ increase of DA-6034 was dependent on the $Ca^{2+}$ entry from extracellular and $Ca^{2+}$ release from internal $Ca^{2+}$ stores. Interestingly, these effects of DA-6034 were related to ryanodine receptors (RyRs) but not phospholipase C/inositol 1,4,5-triphosphate ($IP_3$) pathway and lysosomal $Ca^{2+}$ stores. These results suggest that DA-6034 induces $Ca^{2+}$ signaling via extracellular $Ca^{2+}$ entry and RyRs-sensitive $Ca^{2+}$ release from internal $Ca^{2+}$ stores in epithelial cells.