부연의 연결어미 '-지'의 의미와 용법

최상진,임채훈 한국어학회 2009 한국어학 Vol.42 No.-

In this paper, we inspected meanings and uses of gi the connective ending of Korean Most previous studies asserted that the meaning of gi is contrast But we pointed out the problems of these studies and demonstrated that the meaning of this ending is expatiation The connective ending gi represents that the following clause expatiates and emphasizes the proceeding clause with double negation Because of double negation the forms of the following clauses is fixed and restricted At first, we divided the forms into two kinds the basic and idiomatic forms The basic forms are expressed to the meaning of double negation through various methods double negation rhetorical question, reinterpretation etc. The idiomatic forms is that the proceeding clauses have the idiomatical fixed forms.

6-Exomethylene penamsulfone 유도체의 β-lactamase 저해작용

김해종,여성현,임채욱,임철부,김미영 중앙대학교 약학연구소 1996 약학 논총 Vol.10 No.-

6-Exomethylene penam derivatives were tested as possible β-lactamase inhibitors. The in vitro β-lactamase inhibitory activities were determined by a spectrophotometric assay using Type Ⅰ, Ⅱ, Ⅲ, Ⅳ and TEM β-lactamase. Their activities were compared with sulbactam, tazobactam and clavulanic acid. The 6-exomethylene sulfone derivatives were more potent than clavulanic acid and sulbactam against Type Ⅳ β-lactamase. The Z-isomers showed stronger activities than the E-isomers against TEM and Type Ⅳ β-lactamase.

한국인 제2형 당뇨병 환자의 골격근에서 인슐린 신호전달체계의 결함

최준혁,이관우,김효정,이동훈,이종우,김정은,엄현채,김경미,최성이,정윤석,김현만 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.5

연구배경: 제2형 당뇨병에서 나타나는 인슐린 저항성은 간, 지방, 근육 같은 말초조직에서 인슐린의 작용이 떨어지는 것을 말한다. 제2형 당뇨병의 발생기전에 인슐린 저항성과 인슐린 분비능 저하가 같이 관여함은 잘 알려진 사실이다. 인슐린의 세포내에서의 저항성을 규명하기 위한 인슐린의 세포내 신호전달체계에 대한 연구가 활발히 진행되고 있으며 몇몇 연구에서 인슐린 저항성을 가진 골격근육에서 IRS와 관련된 PI3-kinase의 활성감소와 Akt kinase의 활성감소를 보고하고 있으나 아직까지 명확하게 그 기작이 설명되어지지 않고 있다. 본 연구에서는 정상성인, 제2형 당뇨병 환자를 대상으로 경구당부하검사 및 인슐린 클램프검사를 시행하고 인슐린 클램프 검사시 대상인의 근육을 채취하여 인슐린 신호전달 체계(IR-β, IRS, Akt(PKB, Rac) kinase, GSK-3)를 연구하였다. 방법: 연구대상자는 한국인으로서 경구당부하검사상 정상인 및 당뇨병 환자 각각 11명, 9명을 대상으로 하였으며, 정상인은 건강인으로 과거력상 당대사에 영향을 줄 질환이 없고, 현재 당대사에 영향을 줄 약물 복용 및 다른 소견이 없는 경구당부하검사상 정성 내당능을 보이는 대상자로 하였다. 당뇨병환자는 모두 제2형 당뇨병 환자로 이환기간이 만 5년 이내인 경우로 하고, 인슐린으로 치료하는 대상자는 제외하도록 하였다. 대상자의 연령, 체질량지수, 체지방량, 공복시 총콜레스테롤, 중성지방, 고밀도지단백 콜레스테롤 및 HbA1c, 인슐린, C-peptide를 측정하였고, "HOMA model"을 이용하여 베타세포의 기능와 인슐린저항성 정도를 평가하였다. 정상혈당클램프 검사(euhlycemic hyperinsulinemic clamp test)를 시행하고 인슐린 투입 전과 인슐린 투입 30분후, 두차례에 걸쳐 대퇴부 근육생검을 실시한후 western 법으로 IR-β, IRS, Akt kinase, GSK-3의 인산화량을 측정하였다. 결과: 정상인 11명과 당뇨병 환자 9명을 대상으로 하였으며 대상자의 평균 연령, 평균 체질량지수, 체지방량, 허리/엉덩이 둘레의 비(waist hip ratio; WHR)는 두 군간에 차이가 없었다. 평균 공복혈당은 정상군 98.0±0.3㎎/dL, 당뇨병군 208.1±16.5㎎/dL(p<0.05), HbA1c는 정상군 5.4±0.5%, 당뇨병군 9.2±0.6%(p<0.05)였다. "HOMA model"을 이용한 베타세포의 기능과 인슐린저항성은 정상군 56.4±8.5%, 1.4±0.2, 당뇨병군 72.2±52.3%(p<0.01), 10.2±6.3(p<0.01)였으며 정상혈당클램프 검사상 포도당 이용률은 정상군 8.2±0.6㎎/㎏/min, 당뇨병군 3.7±1.1㎎/㎏/min(p<0.01)로 정상군과 당뇨병군간에 유의한 차이를 나타내었다. Western blot법으로 IR-β, IRS, Akt kinase, GSK-3의 인산화량을 인슐린 투입전과 인슐린 투입 30분후 측정하였을 때 IR-β에서는 정상군이 103.9±2.3에서 241.3±18.6, 당뇨군이 108.9±2.2에서 198.7±6.3으로 증가하였다(p=NS). 이는 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 통계적인 차이가 없었다. IRS에서는 정상군이 111.6±7.3에서 295.6±17.2, 당뇨군이 114.5±6.1에서 222.0±23.2로 증가하였으며(p<0.05), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 24% 감소하였다. Akt kinase에서는 103.4±6.0에서 416.8±29.5로 증가하였으며(p<0.01), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 43% 감소하였다. GSK-3에서는 정상군이 107.7±6.7에서 595.7±28.1, 당뇨군이 104.3±4.8에서 443.3±12.9로 증가하였으며(p<0.01), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 25% 감소하였다. 결론: 제2형 당뇨병 환자에서 정상인과 비교하여 인슐린 자극후 IR-β는 인산화량의 증가정도가 큰 차이가 없었으나, IRS, Akt kinase, GSK-3에서는 인산화량의 증가 정도가 감소되는 것으로 보아 상위 인슐린 신호전단체계부터 결함이 있는 것으로 생각된다. Background: The glucose uptake rate is the limiting step in glucose utilization and storage. The failure of insulin to stimulate glucose uptake in muscle appears to be a primary defect of insulin resistance. This study was undertaken to examine the effect of physiological hyperinsulinemia on the phosphorylation of the insulin receptor (IR-β), insulin receptor substrate (IRS), Akt kinase and GSK-3 in isolated skeletal muscle, in people with type 2 diabetes(n=9) and control subjects(n=11). Methods: 75g OGTT and euglycemic hyperinsulinemic clamp test were done. And vastus lateralis muscle was obtained before and 30 min into the euglycemic clamp. Western blots were performed for tyrosine phosphroylation of insulin receptor substrate (IRS) and phosphorylation of the insulin receptor(IR-β), Akt and GSK-3. Result: There were no statistical differences in the mean age, BMI and body fat between the control subjects and diabetic patients. The fasting blood sugar and HbA_1c in controls and diabetic patients were 98.0±0.3 and 208.1±16.5ng/dl, and 5.4±0.5 and 9.2±0.6%, and 1.4±0.2 in the control subjects, and 72.2±52.3%(p<0.01) and 10.2±6.3(p<0.01) in the diabetic patients, respectively. The insulin resistance from the euglycemic hyperinsulinemic clamp test were 8.2±0.6㎎/㎏/min and 3.7±1.1ng/㎏/min in the control subjects and in the diabetic patients, respectively(p<0.01). Compared with the normal controls, insulin-stimulated IR phosphorylation was no different to that in the diabetic patients. However, insulin-stimulated IRS phosphorylation, insulin-stimulated Akt phosphorylation and insulin-stimulated GSK-3 phosphorylation were reduced in the diabetic patients compared with the normal controls by 24, 43 and 25%, respectively(p<0.05). Conclusion: In Korean type 2 diabetic patients, the insulin resistance may be due to the impairment of the upstream insulin signal molecular network. Further studies will focus on determining whether these signaling defects are the cause of the development of insulin resistance, or secondary to the altered metabolic state, associated with type 2 diabetes mellitus (J Kor Soc Endocrinol 17:685∼697, 2002).

Poster Session 1 : Oral Presentation ; Metabolism and Enzymology : Functional expression of human cytochromes P450 2A6 and 2E1 in Escherichia coli

( Sung Kun Yim ),( Tae Ho Ahn ),( Heung Chae Jung ),( Jae Gu Pan ),( Chul Ho Yun ) 한국생화학분자생물학회 (구 한국생화학회) 2005 62회 KSBMB Annual Meeting in 2005 Vol.- No.-

Poster Session 1 : A continuous spectrophotometric assay for NADPH-cytochrome P450 reductase activity using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliu m bromide

( Sung Kun Yim ),( Tae Ho Ahn ),( Heung Chae Jung ),( Jae Gu Pan ),( Chul Ho Yun ) 한국생화학분자생물학회 (구 한국생화학회) 2005 생화학분자생물학회 춘계학술발표논문집 Vol.2005 No.-

A Continuous Spectrophotometric Assay for NADPH-cytochrome P450 Reductase Activity Using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide

Yim, Sung-Kun,Yun, Chul-Ho,Ahn, Tae-Ho,Jung, Heung-Chae,Pan, Jae-Gu Korean Society for Biochemistry and Molecular Biol 2005 Journal of biochemistry and molecular biology Vol.38 No.3

NADPH-cytochrome P450 reductase (CPR) transfers electrons from NADPH to cytochrome P450 and also catalyzes the one-electron reduction of many drugs and foreign compounds. Various spectrophotometric assays have been performed to examine electron-accepting properties of CPR and its ability to reduce cytochrome $b_5$, cytochrome c, and ferricyanide. In this report, reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) by CPR has been assessed as a method for monitoring CPR activity. The principle advantage of this substance is that the reduction of MTT can be assayed directly in the reaction medium by a continuous spectrophotometric method. The electrons released from NADPH by CPR were transferred to MTT. MTT reduction activity was then assessed spectrophotometrically by measuring the increase of $A_{610}$. MTT reduction followed classical Michaelis-Menten kinetics ($K_m\;=\;20\;{\mu}M$, $k_{cat}\;=\;1,910\;min^{-1}$). This method offers the advantages of a commercially available substrate and short analysis time by a simple measurement of enzymatic activity of CPR.

Molecular Targets of Genistein and Its Related Flavonoids to Exert Anticancer Effects

Chae, Hee-Sung,Xu, Rong,Won, Jae-Yeon,Chin, Young-Won,Yim, Hyungshin MDPI 2019 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.20 No.10

<P>Increased health awareness among the public has highlighted the health benefits of dietary supplements including flavonoids. As flavonoids target several critical factors to exert a variety of biological effects, studies to identify their target-specific effects have been conducted. Herein, we discuss the basic structures of flavonoids and their anticancer activities in relation to the specific biological targets acted upon by these flavonoids. Flavonoids target several signaling pathways involved in apoptosis, cell cycle arrest, mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/AKT kinase, and metastasis. Polo-like kinase 1 (PLK1) has been recognized as a valuable target in cancer treatment due to the prognostic implication of PLK1 in cancer patients and its clinical relevance between the overexpression of PLK1 and the reduced survival rates of several carcinoma patients. Recent studies suggest that several flavonoids, including genistein directly inhibit PLK1 inhibitory activity. Later, we focus on the anticancer effects of genistein through inhibition of PLK1.</P>

A Continuous Spectrophotometric Assay for NADPH-cytochrome P450 Reductase Activity Using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide

Sung Kun Yim,Chul Ho Yun,Tae Ho Ahn,Heung Chae Jung,Jae Gu Pan 한국생활환경학회 2005 BMB Reports Vol.38 No.3

Mangosteen Extract Attenuates the Metabolic Disorders of High-Fat-Fed Mice by Activating AMPK

Chae, Hee-Sung,Kim, Young-Mi,Bae, Jin-Kyung,Sorchhann, Sochivak,Yim, Sreymom,Han, Ling,Paik, Jin Hyub,Choi, Young Hee,Chin, Young-Won Mary Ann Liebert, Inc. Publishers 2016 Journal of Medicinal Food Vol. No.

<P>This study investigated the effects of mangosteen on metabolic syndromes in high-fat (HF) diet-fed mice and the underlying mechanisms related to adipogenesis. Mangosteen-supplemented mice gained significantly less body weight, compared with the HF group. The levels were markedly elevated in HF mice for serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, glucose, triglyceride, total cholesterol, low-density lipoprotein (LDL) cholesterol, and free fatty acid; whereas these levels were significantly lower in the 200mg/kg of the mangosteen extract-treated group. The mangosteen extract did not modify high-density lipoprotein (HDL)-cholesterol, however, LDL-cholesterol was lower and HDL/LDL ratio was higher (9.4 vs. 3.7 in HF group). Furthermore, 200mg/kg of mangosteen treatment activated the hepatic AMP-activated protein kinase and Sirtuin 1 in an in vivo system. Thus, the results of this study suggest that mangosteen extract exerts antiobesity effects by regulating energy metabolism and hepatic lipid homeostasis.</P>

HBV : Application of Roadmap-concept on Chronic Hepatitis B Patient with Entecavir Therapy Previously Exposed to Lamivudine: A Long Term Follow-up Study

( Sang Jun Suh ),( Hyung Joon Yim ),( Yeon Seok Seo ),( Chang Wook Kim ),( Chang Don Lee ),( Sang Hoon Park ),( Myung Seok Lee ),( Choong Kee Park ),( Hee Bok Chae ),( Moon Young Kim ),( Soon Koo Baik 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background/Aim: Many patients with lamivudine-resistant (LAM-R) chronic hepatitis B (CHB) had been treated by switching to entecavir (ETV) 1.0mg. Although rate of resistance to ETV (ETV-R) is reported high, current medical insurance system doesn`t pay-back for change from ETV to other agent in patients whose resistance to ETV was not identified. This study was aimed to stratify ETV therapy in LAM-R patients. Methods: One hundred and ten CHB patients who occurred LMV-R and received ETV 1.0mg up to 5 years were evaluated prospectively. At 12 months of switching to ETV, we divided subjects into non-detection group (HBV DNA<20 IU/mL) and detection group (HBV DNA≥20 IU/mL), which was subdivided into low viral load group (20≤HBV DNA<2,000 IU/mL) and high viral load group (2,000 IU/mL≤ HBV DNA). Virologic response rate (VR; HBV DNA<20 IU/mL) and ETV-R were evaluated as end point. Results: One hundred and ten patents were enrolled. The mean age was 45±11years, the proportion of male and HBeAgpositive patient was 71% (80/110) and 77% (85/110), respectively. The mean serum HBV DNA levels were 6.89±1.03, 3.26±1.81, 3.06±1.82, 2.49±1.53, 2.43±1.35 and 1.73±0.87 log10IU/ ml at baseline, month 12, 24, 36, 48 and 60, respectively. The VR (95% vs. 29%, P<0.001) was higher and ETV-R (10% vs. 54%, P=0.001) was lower in non-detection group than in detection group. The VR (27% vs. 29%, P=0.853) and ETV-R (45% vs. 57%, P=0.367) was not significantly different between low viral load and high viral load group. Resistance to ETV occurred at 26±10.3 months (median 24 months, 12-48 months) in detection group. Conclusion: Resistance rates were high in patients with detectable HBV DNA at 12 months of ETV therapy. Therefore, switching to or adding a potent nucleotide analogue (e.g. tenofovir) is warranted in LAM-R CHB patients whose HBV DNA is detected after 12 months of ETV therapy.