G₁ to S phase transition protein 1 induces apoptosis signal-regulating kinase 1 activation by dissociating 14-3-3 from ASK1

Lee, J A,Park, J E,Lee, D H,Park, S G,Myung, P K,Park, B C,Cho, S Nature Publishing Group 2008 Oncogene Vol.27 No.9

Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase kinase kinase family, plays a critical role in mediating apoptosis signals initiated by a variety of death stimuli such as hydrogen peroxide and tumor necrosis factor-α. Owing to its critical role in inducing apoptosis, the activity of ASK1 is tightly regulated by various mechanisms such as post-translational modifications and protein–protein interactions. Here we describe the identification of G<SUB>1</SUB> to S phase transition protein 1 (GSPT1), which is associated with protein translation, as a regulator of ASK1. GSPT1 interacts with ASK1 and enhances ASK1-induced apoptotic activity through the activation of caspase-3. In vitro kinase assay data show that GSPT1 enhances ASK1 autophosphorylation and its kinase activity. Cell cycle-dependent GSPT1 induction and small interfering RNA analyses show that ASK1 autophosphorylation is dependent on the expression level of endogenous GSPT1 in cells. GSPT1 inhibits the binding of ASK1 to the 14-3-3 protein, an ASK1 inhibitor, while GSPT1 has no effect on the interaction between ASK1 and TRAF2, a C-terminal-binding activator of ASK1. Thus, our results reveal a novel role of GSPT1 in the regulation of ASK1-mediated apoptosis.Oncogene (2008) 27, 1297–1305; doi:10.1038/sj.onc.1210740; published online 20 August 2007

Radiolysis of Paraffin Encapsulation Wax

Chang Lak Kim,Myung Chan Lee,Won Jae Park,Tae Won Suk,William G. Burns 대한방사선방어학회 1995 방사선방어학회지 Vol.20 No.4

Dose-dependent pharmacokinetics and first-pass effects of mirodenafil, a new erectogenic, in rats

Choi, Young H.,Lee, Young S.,Bae, Soo H.,Kim, Tae K.,Lee, Bong-Y.,Lee, Myung G. John Wiley Sons, Ltd. 2009 Biopharmaceutics & drug disposition Vol.30 No.6

<P>The pharmacokinetics of mirodenafil and its two metabolites, SK3541 and SK3544, after intravenous (5, 10, 20 and 50 mg/kg) and oral (10, 20 and 50 mg/kg) administration of mirodenafil, and the first-pass effect of mirodenafil after intravenous, oral, intraportal, intragastric and intraduodenal (20 mg/kg) administration of mirodenafil were evaluated in rats. The pharmacokinetics of mirodenafil and SK3541 were dose-dependent after both intravenous and oral administration of mirodenafil due to the saturable hepatic metabolism of mirodenafil. After oral administration of mirodenafil, approximately 2.59% of the oral dose was not absorbed, the F value was approximately 29.4%, and the hepatic and gastrointestinal first-pass effects of mirodenafil were approximately 21.4% and 54.3% of the oral dose, respectively. The low F value of mirodenafil in rats was mainly due to considerable hepatic and gastrointestinal first-pass effects in rats. The equilibrium plasma-to-blood cell partition ratios of mirodenafil were independent of the initial blood mirodenafil concentrations of 1–10 µg/ml; the mean values were 1.08–1.21. The plasma binding values of mirodenafil to rat plasma was 87.8%. Copyright © 2009 John Wiley & Sons, Ltd.</P>

신경내분비분화를 보인 소아 부신피질종양-1예 보고-

송상용,이승숙,명나혜,지제근,송상용,이승숙,명나혜,지제근 대한병리학회 1993 Journal of Pathology and Translational Medicine Vol.27 No.2

Meckel氏 憩室에 發生한 纖維腫 : 一例報告 A case report

李尙國,咸毅根,池堤根,金聖九,梁文浩,趙明河,朱興在 中央醫學社 1965 中央醫學 Vol.8 No.4

This is a case report of a fibroma of Meckel's diverticulum in a 56 year old. Korean female. The diverticulum was located in ileum 50 cm from the ileocecal valve, roughly along the antimesenteric border and measuring 2 cm in length. The tumor was. located at the tip of Meckel's diverticulum forming a large pedunculated mass with the diverticular stalk. And microscopically the tumor appeared to be arised from submucous connective tissue and the tumor was well encapsulated and measured 11 x 8 x 7, 5cm, in maximum dimensions, with hard consistency. Microscopically, the tumor was entirely comprised of loose and dense fibrous connective tissue with more or less vascular structures. No evidence of malignancy was present. The diverticulum revealed ileal type mucosa and replacing tumor masses. No heterotopic tissues were identified in the sections. Authors assume that this is the first published case of the fibroma of Meckel's diverticulum in this country.

Electron Cyclotron Resonance O_2 Plasma에서 증착한 규소 산화 박막의 특성

안명환,서문석,장재선,서성모,이기방,윤창주,이형재,남기석,최규현,손춘배,김용섭,강석희 全北大學校 基礎科學硏究所 1994 基礎科學 Vol.17 No.-

규소 산화막을 ECR-CVD(electron cyclotron resonance-chemical vapor deposition) 증착방법으로 5인치 기판위에 상온에서 증착하고, 증착공정조건인 증착율, 기판온도, 마이크로파의 세기변화 및 플라즈마 혼합기체의 비에 따른 규소 산화막의 특성을 조사하였다. 또한 산화막의 구조적인 특성을 비교하기 위해 FTIR을 이용하여 ECR-CVD 증착한 산화막, RPE-CVD(remote plasma enhanced-CVD) 증착한 산화막 및 열 산화막의 stretching frequency를 측정하였다. 측정된 결과 ECR-CVD로 증착된 산화막이 구조적인 면에서 열 산화막과 거의 같음을 보였다. ECR-CVD로 증착된 산화막의 전기적인 특성을 전류-전압 및 축전-전압 측정에의하여 분석하였다. 축전된 산화막의 전기적인 특성은 산화막의 전하 밀도는 1×10 exp (11)/㎠이였고, 평균 절연 파괴 전압은 약 6 MV/㎝이다. We have grown thin films of SiO_2 at room temperature by using an ECR-CVD system and have investigated the changes in the properties of the deposited films with changes in the processing conditions such as the deposition rate, the substrate temperature, the microwave power and the plasma gas mixing ratio. We also measured the stretching frequency of three kinds of oxides, and ECR-CVD-grown oxide, a PECVD-grown oxide, and a thermally grown oxide, using FTIR analysis to compare their structural properties. The result shows that the structural properties of the ECR-grown oxide are similar to those of the thermally grown oxide. Additionally, the electrical properties of the ECR-grown oxide were investigated by using current-voltage and capacitance-voltage measurements. These electrical results indicate that the oxide charge density and the average breakdown voltage are 1×10 exp (11) ㎝^-2 and 6 MV/㎝, respectively.

Radiolysis of Paraffin Encapsulation Wax

Kim,Chang Lak,Lee,Myung Chan,Park,Won Jae,Suk,Tae Won,Burns,William G. 대한방사선 방어학회 1995 방사선방어학회지 Vol.20 No.4

파라핀 왁스를 사용하여 건조된 농축폐액을 고화시킬 경우, 방사선적 가수분해에 의해 발생할 가능성이 있는 수소가스의 발생량을 추정하여 보았다. 분석결과에 의하면, 코발트 60의 방사선에너지에 의해 방사선적 가수분해가 주로 발생ㄹ함을 알 수 있다. 200리터 드럼붕 120 리터가 파라핀으로채워졌다고 가정할 때 수소가스 발생은 초기에 4.4 ×10²cm³yr¹이고 100년이 경과한 후는 7.2cm³yr¹로 줄어든다. 수소에 의한 발화점을 25년이 경과한 후 도달할 가능성이 있느나, 폭발한계에는 1000년 이내에 도달할 가능성이 없다. 안전성 관련 주요 한계점이 도달하는 시기는 드럼내 파라핀 왁스의 채움 정도에 매우 민감하게 영향을 받는다. 드럼내 공간의 감소시, 발화점에 도달 시간이 줄어듬을 알수 있다. An estmate is made on the potential generation rate of H₂from radiolysis of the paraffin-wax encapsulant proposed for the solidified liquid concentrate wasteform. The results show tht the radiolytic production of H₂from paraffin-wax-encapsulated waste is dominated by the radiation energy released from ?Co. The radioltic production of H₂will proceed at an initial rate equivalent to aproximately 4.4 ×10²cm³yr¹in 200 litre drums that are partly filled with 120 litres of encapsulated waste. The gas production rate will fall to a value of 7.2cm³yr¹after 100 years. The lower flammable limit for H₂in air will be reached in about 25 years and the lower explosive limit for H₂in air would not be reached in 1000 years. The timescale in which these safety-related limits are reached is strongly dependent on the level of filling of each waste drum. A reduction of the air space inside each drum would reduce the time required to reach the lower flammable limit.

Inhibitory effect of a novel naphthoquinone derivative on proliferation of vascular smooth muscle cells through suppression of platelet-derived growth factor receptor β tyrosine kinase

Kim, Y.,Han, J.H.,Yun, E.,Jung, S.H.,Lee, J.J.,Song, G.Y.,Myung, C.S. North-Holland ; Elsevier Science Ltd 2014 european journal of pharmacology Vol.733 No.-

This study was designed to investigate the antiproliferative effect of a novel naphthoquinone derivative, 2@?undecylsulfonyl@?5,8@?dimethoxy@?1,4@?naphthoquinone (2-undecylsulfonyl-DMNQ), on platelet-derived growth factor (PDGF)-stimulated vascular smooth muscle cells (VSMCs) and examine the possible molecular mechanism of its antiproliferative action. 2-Undecylsulfonyl-DMNQ significantly inhibited PDGF-stimulated cell number and DNA synthesis, and arrested the PDGF-stimulated progression through G<SUB>0</SUB>/G<SUB>1</SUB> to S phase of cell cycle supported by the suppression of pRb phosphorylation and cyclin D1/E, CDK2/4 and PCNA expressions. 2-Undecylsulfonyl-DMNQ dose-dependently inhibited the PDGF-stimulated phosphorylation of phospholipase Cγ (PLCγ), protein kinase B (Akt/PKB), signal transducers and activators of transcription 3 (STAT3) and extracellular signal-regulated kinase ½ (ERK ½). In addition, 2-undecylsulfonyl-DMNQ inhibited PDGF-induced PDGF receptor β (PDGF-Rβ) dimerization and the phosphorylation of Tyr<SUP>579/581</SUP>, Tyr<SUP>716</SUP>, Tyr<SUP>751</SUP> and Tyr<SUP>1021</SUP> in PDGF-Rβ. However, 2-undecylsulfonyl-DMNQ has no antiproliferative effect on epidermal growth factor (EGF)- or fetal bovine serum (FBS)-stimulated VSMCs. In conclusion, these findings suggest that the antiproliferative effects of 2-undecylsulfonyl-DMNQ on PDGF-stimulated VSMCs are due to the blockade of receptor dimerization and autophosphorylation on specific tyrosine residues of PDGF-Rβ, which resulted in the subsequent suppression of signaling cascades and a cell cycle arrest. Our observation may explain an important mechanism to block the integration of multiple signals generated by growth factor receptor activation for prevention of VSMC proliferation in cardiovascular diseases.

Cyclosporine 제제간의 생물학적 동등성 비교

김민정,박경호,신완균,이명걸,김성기,최진석 한국병원약사회 1995 병원약사회지 Vol.12 No.3

Cyclosporine(CyA) is a neutral, hydrophobic cyclic endecapeptide that has very potent immunosuppressive activity and used to prevent graft rejection and to treat autoimmune diseases. Cyclosporine is absorbed slowly and incompletely from the upper small bowel and pharmacokinetic parameters has variability depends on pharmaceutical formulation. For these reasons, pharmacokinetic evaluation of newly formulated cyclosporine is necessary to safe and rational application after transplantation. In this study, the bioequivalence in cyclosporine between the Sandimmun^(R)(SandozCo.) and Implanta^(R)(Hanmi pharma. Co.) Soft capsule was done, 14 normal volunteers(age 19 to 24 YO, 12 healthy males and 2 females) was divided into two groups, and a randomized, cross-over study was employed. Cycolosporine pharmacokinetic parameters(Cmax, Tmax, AUC) were evaluated and ANOVA was utilized for the stastical analysis in parameters, after 400㎎ of oral administration of each formulation. Cmax is 1162±350ng/㎖(C.V30%) in Sandimmun^(R)and 893±174ng/㎖(C.V 19.4%) in Implanta^(R), Tmax is 2.46±0.93hr(C.V37.8%) and 2.71±0.61hr(C.V 22.5%), and AUC is 6126±1591ng.hr/㎖(C.V 25.9%) and5594±1085ng.hr/㎖(C.V 19.4%), respectively. As the result of the data, Implanta of Hanmi has a slower absorption rate than Sndimmun of Sandos, but they are equal in the quantity of absorption. Cmax is lower, and Tmax is later in Implanta than in Sandimmun because of the slower absorption of Implanta. And these can be a considerable difference statistically, but these are no actual problem at a clinical standpoint. Conversely, the lower CV in these parameters in every individual can be a merit.

Negligible pharmacokinetic interaction between oral DA-8159, a new erectogenic, and amlodipine in rats

Lee, Joo H.,Kim, Eun J.,Kwon, Jong W.,Yoo, Moohi,Lee, Myung G. John Wiley Sons, Ltd. 2006 Biopharmaceutics & drug disposition Vol.27 No.3

<P>A pharmacokinetic interaction between oral DA-8159 and amlodipine was evaluated in male Sprague–Dawley rats. In rats pretreated with troleandomycin (a main inhibitor of CYP3A1/2 in rats), the AUC<SUB>0−6 h</SUB> of amlodipine was significantly greater than the controls (34.5±6.01 compared with 28.0±4.70 µg min/ml), indicating that amlodipine is metabolized via CYP3A1/2 in rats. It was reported that the metabolism of DA-8159 and the formation of DA-8164 (a metabolite of DA-8159) were mainly mediated via CYP3A1/2 in rats, and amlodipine significantly inhibited the CYP3A2 in rats. Therefore, a pharmacokinetic interaction between the two drugs could be expected. However, after oral administration of DA-8159 at a dose of 30 mg/kg with or without oral amlodipine at a dose of 5 mg/kg to rats, the pharmacokinetic parameters of DA-8159 and DA-8164 were not significantly different between the two groups of rats. Similar results were also obtained from amlodipine between with and without DA-8159. The above data indicated that the pharmacokinetic interaction between oral DA-8159 and amlodipine was almost negligible in rats. Copyright © 2006 John Wiley & Sons, Ltd.</P>