고포도당이 백서 사구체 메산지움 배양세포에서 p38 MAPK 활성화 및 Fibronectin 생성에 미치는 영향

유태현 ( Yu Tae Hyeon ),허종호 ( Heo Jong Ho ),류동열 ( Lyu Dong Yeol ),김현욱 ( Kim Hyeon Ug ),이수현 ( Lee Su Hyeon ),김진주 ( Kim Jin Ju ),정동섭 ( Jeong Dong Seob ),최규헌 ( Choe Gyu Heon ),이호영 ( Lee Ho Yeong ),한대석 ( Han 대한신장학회 2003 Kidney Research and Clinical Practice Vol.22 No.5

목 적 : 고포도당으로 자극한 백서 메산지움 배양세포에서 p38 mitogen activated protein kinase (MAPK)의 활성화와 p38 MAPK의 상부와 하부인자로 알려져 있는 MAPK kinase 3/6 (MKK3/6)와 c-AMP responsive element binding protein (CREB)의 활성화, 그리고 fibronectin 합성을 자극 시간에 따라 관찰하고, p38 MAPK 경로와 fibronectin 합성 사이의 연관성을 규명함으로서 당뇨병성 신증의 병태생리를 규명하고자 하였다. 방 법 : 백서 메산지움 배양세포를 정상 포도당 (5.6 mM), 고포도당 (30 mM), 또는 정상 포도당+만니톨 (24.4 mM)로 자극한 후 첫째 p38 MAPK; 둘째 p38 MAPK의 상부 인자인 MKK3/6; 셋째 p38 MAPK의 하부인자인 CREB; 넷째 MAPK phosphatase-1 (MKP-1)의 변화를 자극 시간 (3분-48시간)에 따라 Western blot을 이용하여 관찰하였으며, 다섯째 fibronectin의 변화는 RT-PCR과 ELISA를 이용하여 확인하였다. 결 과 : 고포도당으로 자극한 백서 사구체 메산지움 배양세포에서 p38 MAPK 경로가 활성화 되었다. Total p38 MAPK 단백은 변화가 없었으나, 활성화된 phospho-p38 MAPK 단백은 고포도당군에서 자극 10분 후부터 정상 포도당군에 비해 의의있게 증가되었으며 (평균 1.9배), phospho-CREB 단백 역시 고포도당군에서 자극 10분 후부터 의미있게 증가되었다 (평균 2.5배). 이에 비해 p38 MAPK의 상부인자인 phospho-MKK3/6는 고포도당군에서 자극 3분 후부터 의의있게 증가되었다 (평균 2.4배). 또한, MKP-1 단백 발현은 고포도당군에서 p38 MAPK의 활성이 증가하기 시작한 시기와 동일한 시기 (자극 10분 후)부터 증가하기 시작하였다 (평균 1.9배). Fibronectin mRNA와 세포 배양액내 fibronectin은 고포도당군에서 자극 48시간 후에 각각 1.7배와 1.5배 증가되었으며, 이러한 증가는 p38 MAPK 억제제인 SB203580 (1 μM)에 의해 각각 73%와 69% 억제되었다. 결 론 : 고포도당으로 자극한 백서 사구체 메산지움 배양세포에서 p38 MAPK 경로의 활성화를 확인하였으며, p38 MAPK 억제제가 고포도당에 의한 fibronectin의 합성 증가를 억제시키는 것으로 보아 당뇨병성 신증에서 관찰되어지는 fibronectin의 축적에 p38 MAPK 경로가 관여할 것으로 생각된다. Background : The p38 mitogen-activated protein kinase (MAPK) pathway is activated by several stress factors, potentially leading to cellular apoptosis and growth. Little is known about the pattern of p38 MAPK pathway activation in mesangial cells under high glucose conditions. We examined the activity and expression of p38 MAPK members, 1x78 MAPK, MAPK kinase 3/6 (MKK3/6), c-AMP responsive element binding protein (CREE), and MAPK phosphatase-l (MKP-1) in cultured rnesangial cells exposed to high glucose. Methods : Mesangial cells were subcultured from rat glomeruli isolated by sieving technique. After serum restriction for 48 hours rnesangial cells were exposed to 5.6 mM glucose (low glucose, LG), 5.6 mM glucose+24.4 mM mannitol (LG+M), or 30 mM glucose (high glucose, HG) for 3 minutes to 48 hours with or without SU203580. Western blot was performed to determine the activity and protein expression of p38 MAPK members. R`I-I`CR and ELISA were performed for fibronectin mRNA expression and fibronectin synthesis, respectively. Results : p38 MAPK and CREB activities were significantly increased in rnesangial cells exposed to FIG compared with LG or LG+M after 10 minutes and was sustained at higher levels to 48 hours (p<0.05), but total p38 MAPK and CREB protein expressions did not differ. MKP--1 showed a similar pattern as p 3 MAPK and CREE (p<O.O.i). MKK3/6 acitvity was significantly higher in HG cells after 3 minutes and remained at higher levels throught the study period (p<0.05). Fibronectin mRNA expression and fibronectin synthesis were significantly increased in mesangial cells exposed to HG after 48 hours (p<0.05). SB203580 (1 pM) pretreatment for 1 hour significantly reduced HG-induced fibronectin mRNA expression and fibronectin synthesis by 73% and 69%, respectively (p<0.05). Conclusion : p38 MAPK activity was increased in mesangial cells exposed to HG in parallel with increased MKK3/6 activity, resulting in CREB activation and increased fibronectin synthesis. This activated p38 MAPK may play a role in the pathogenesis of diabetic nephropathy.

Inhibition of oxidative stress induced‑cytotoxicity by coptisine in V79‑4 Chinese hamster lung fibroblasts through the induction of Nrf‑2 mediated HO‑1 expression

Hyeon‑Gyun Jo,Cheol Park,이혜숙,Gi‑Young Kim,Young‑Sam Keum,Jin Won Hyun,Taeg Kyu Kwon,Yung Hyun Choi,Su Hyun Hong 한국유전학회 2021 Genes & Genomics Vol.43 No.1

Background Coptisine is a natural alkaloid compound and is known to have multiple benefcial efects including antioxidant activity. However, whether it can protect lung fbroblasts from oxidative damage has not been studied yet. Objectives To investigate the potential inhibitory efect of coptisine against oxidative stress in V79-4 lung fbroblast cells. Methods V79-4 cells were treated with H2O2 (1 mM) in the presence or absence of coptisine (50 µg/ml), N-acetyl cysteine (NAC, 10 mM) or zinc protoporphyrin IX (ZnPP, 10 µM) for the indicated times. The alleviating efects of coptisine on cytotoxicity, cell cycle arrest, apoptosis, reactive oxygen species (ROS) production, DNA damage, mitochondrial dynamics, and inhibition of ATP production against H2O2 were investigated. Western blot analysis was used to analyze the expression levels of specifc proteins. Results Coptisine inhibited H2O2-induced cytotoxicity and DNA damage by blocking abnormal ROS generation. H2O2 treatment caused cell cycle arrest at the G2/M phase accompanied by increased expression of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1 and decreased expression of cyclin B1 and cyclin A. However, these efects were attenuated in the presence of coptisine or NAC. Coptisine also prevented apoptosis by decreasing the rate of Bax/Bcl-2 expression in H2O2-stimulated cells and suppressing the loss of mitochondrial membrane potential and the cytosolic release of cytochrome c. In addition, the activation of nuclear factor-erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was markedly promoted by coptisine in the presence of H2O2. However, zinc protoporphyrin IX, a potent inhibitor of HO-1, attenuated the ROS scavenging and anti-apoptotic efects of coptisine. Conclusions Based on current data, we suggest that coptisine can be used as a potential treatment for oxidative stress-related lung disease.

진행성 폐 종양 환자에서 종양 내 OK-432 주입술의 효과

정수현,김성빈,박진희,탁희상,옥철호,장태원,정만홍,천봉권 고신대학교 의과대학 2009 고신대학교 의과대학 학술지 Vol.24 No.2

Background: Intratumoral injection of OK-432 produced significant antitumor effects. There are reports that OK-432 was injected directly into tumor tissue on gastrointestinal tracts and HCC tissue, producing decrease in serum alpha-fetoprotein level. We adopted this technique for treating locally advanced lung cancer. The object of this study is to evaluate the local therapeutic efficacy, side effects of injection for treating symptomatic mass. Methods: Twenty lung cancer patients (13 males and 7 females) underwent sonography guided OK-432 injection. We analyzed relationships between response of OK-432 and response of skin test, histology and age. Pain that patients feel was evaluated by VAS (Visual Analog scale). Results: A significant decrease of tumor size was observed. The mean pre-injection diameter of the lesions was 54.7±11.3mm, PR rate were 15.0% (3/20) and minimal change (50%<tumor size decreased.) patients were 35.0% (7/20). The VAS score before injecting OK-432 into the lesion was 5±3, this was decreased to 2.5±1.5 (p=0.04). Object response was significantly correlated with skin response, adenocarcinoma, and age. Conclusion: A significant decrease of tumor size and pain was observed. So OK-432 is a valuable treatment option for patients with symptomatic lesion from advanced lung cancer who are not amenable to further therapy.

‘스탠리 돈우드 앨범아트웍’전시 공간 디자인 프로세스에 관한 연구 - 라디오헤드 ‘A Moon Shaped Pool’ 앨범아트 작품을 중심으로 -

박수현,이진민,신은별 숙명여자대학교 디자인연구소 2018 숙명디자인학 연구 Vol.25 No.-

본 연구는 공간 디자인 스튜디오 II 수업에서 진행한 전시 공간 디자인 프로세스에 관한 연구로서, 디자인 요소와 원리를 바탕으로 조형(造形)의 평면(2D),입체(3D), 공간(4D)으로 나아가는 차원의 확장을 통한 전시공간 디자인 프로젝트이다. 본 연구는 크게 세가지로 나뉜다. 첫째, 스탠리 돈우드와 그의 작품세계를 분석하고 둘째, 그의 시각적 조형 언어를 재구성하여 평면작업으로서 그의 전시 포스터를 만든 후 이를 바탕으로 입체조형을 한다. 셋째, 스탠리 돈우드의 작품에서 추출한 색채 및 재질을 적용시키고 입체조형에 기-승-전-결의 이야기 구성과 기능을 적용해 전시 공간을 계획한다. 이를 평면, 조닝, 동선 등을 도면과 다이어그램으로 구체적으로 표현하고 이에 따른 결과물을 판넬과 모형으로 정리하였다. 끝으로 본 연구는 평면으로부터 공간까지의 조형적 탐구에 기초한 디자인 프로세스로 기능적 공간디자인에서 벗어나 형태적 조형미를 갖춘 공간 디자인 프로세스 개발에 있어 향후 기초자료로서 활용 가치가 있다.

고등학교 국어교육에서의 시문학교육의 개선 방안

박진태,김현수 大邱大學校 師範大學 附設 敎育硏究所 2010 學校敎育硏究 Vol.5 No.2

The integration between the classical literature education and the contemporary literature education, between the Korean language education and the literature education, and between the understanding education and the expressing education is necessary and compulsory for the histories of both the Korean language education and the literature education. Understanding this issue, this paper aimed to materialize the speaking and writing methods of the Korean poems including <Chengsanbaylgok>, <Ubusasisa>, <The Azaleas>, <A Glass Window>, <Wilderness>, to suggest ways to apply these methods to the expressing education. Also the paper designed plans to strengthen the ability to express the beauty of poetry through a critical writing and presentations. <Chengsanbaylgok> is a “travel writing” in that the speaker directly moves his or her space, and <Ubusasisa> is a “cinematic writing” in that the speaker's view is shifted by the poet. <The Azaleas> is a “performance writing” in that it includes ceremonial behaviors, and <A Glass Window> is a “healing writing” in that the speaker is self-healing as establishing his or her view on life and death. Finally, <Wilderness> is a “historical writing” in that it describes the pastpresent- future of a wilderness. 표현교육의 통합은 국어교육사적으로, 또 문학교육사적으로 필요성과 당위성을 지닌다. 이러한 문제의 식을 가지고 <청산별곡>, <어부사시사>, <진달래꽃>, <유리창>, <광야>의 말하기/글쓰기 방식을 유형화 하고, 이를 표현교육에 활용하는 방안을 제시하고, 아울러 비평문 쓰기와 발표활동을 통하여 시의 아름 다움을 표현하는 능력을 신장시키는 방안을 구안하였다. <청산별곡>은 시적 화자가 공간을 이동하는 점 에서 기행적 글쓰기이고, <어부사시사>는 화자의 시점을 이동시키는 점에서 영화적 글쓰기이고, <진달 래꽃>은 의례적 행동을 하는 점에서 공연적 글쓰기이고, <유리창>은 화자가 생사관을 정립하면서 자기 치유를 하는 점에서 치유적 글쓰기이고, <광야>는 광야의 과거-현재-미래를 서술하는 점에서 역사적 글쓰기이다.

수도권 지역 대학병원과 재활병원의 인턴물리치료사간 인턴 만족도 비교

강순희,전수진,정민현,정은송,이범승,최용진 韓國交通大學校 2013 한국교통대학교 논문집 Vol.48 No.-

The purpose of this study was to compare internship satisfaction of intern physical therapists working in the university hospitals with that of them working in the rehabilitation hospitals in Seoul metropolitan area. The questionnaire for internship satisfaction survey that amended from vocational interest test [Strong Interest Inventory(SII)] was used to examine satisfaction of intern physical therapists and the questionnaire was used to ask general characteristics, educational and work environment. Thirty nine intern physical therapists working in university hospital and fifty nine intern physical therapists rehabilitation hospital in Seoul metropolitan area responded. Frequency analysis, χ² test and independent t-test were conducted to evaluate differences between groups about variables of internship satisfaction survey, general characteristics, work and educational environments with using the PASW 18.0 statistical program. The results of the study were as follows. There were significant differences of intern physical therapists between university hospitals and rehabilitation hospitals in overall scores of internship satisfaction and scores of all sub-items such as duty, supervision, working condition, work mates and wages. Intern physical therapists working in the university hospitals showed higher satisfaction than that of Intern physical therapists working in the rehabilitation hospitals.

축산 폐수의 효율적 처리를 위한 광합성 미세조류인 Spirulina platensis 배양 공정의 최적화

안주희,김성수,김태호,이준엽,오상집,이진하,이현용 한국미생물생명공학회 ( 구 한국산업미생물학회 ) 1996 한국미생물·생명공학회지 Vol.24 No.4

돈분 폐수의 효율적인 처리를 위해 6 W/㎡, 12 W/㎡와 24 W/㎡의 조도 하에서 온도를 15℃에서 40℃까지 각각 변화시켜, 광합성 미세 조류인 Spirulina platensis의 생육에 관한 최적 생육 조건 결정에 관한 실험을 하였다. 균체의 비생육속도는 30℃까지는 온도 증가에 따라 증가하였다. 균체의 생육에 있어서 온도의 영향을 설명하기 위해서 Arrhenius 식을 이용하여서 얻은 활성화 에너지 값은 13.5kal/mol이었다. 순수 배지에서 배양된 균체의 비생육속도가 0.31(1/day)인 반면 30% 돈분 첨가 배양시 얻은 균체의 비생육속도는 0.24(1/day)였다. 폐수내의 총 질소량과 이의 제거속도로 균체의 폐수 처리 능력을 평가할 수 있었다. 돈분 농도를 달리 첨가한 회분배양에 있어서 70~93%(PO_4^3- -P), 67~93%(inorganic nitrogen), 80~90% (COD) 그리고 37~56%(organic nitrogen)의 감소율을 보였다. 총-질소와 총-인의 1차반응 감소 속도 상수는 각각 0.17(1/day)와 0.14(1/day)로 계산되었다. 20% 돈분을 첨가하는 연속배양에 있어서 회석률이 0.20(1/day)일 때 최대 균체농도가 1.52(g/L)를 유지했다. 돈분처리 후 얻은 균체의 성분은 단백질이 58.7%, 지방 11.0% 그리고 회분이 15.6%였다. The kinetics of growing microalga, Spirulina platensis was investigated to treat swine wastes with optimum growth conditions. Temperature was varied from 15 to 40℃ at three different light intensities, 6 W/㎡, 12 W/㎡ and 24 W/㎡. The specific growth rate was increased as temperature increased up to 30℃. The activation energy was estimated as 13.5 kcal/mol by an Arrhenius relationship. 0.24(1/day) of specific growth rate was obtained from batch cultivation with 30% swine wastes, compared to 0.31 (1/day) from clean culture. It was found that Spirulina platensis was able to reduce 70~93% of PO_4^3- -P, 67~93% of inorganic nitrogen, 80~90% of COD and 37~56% organic nitrogen by adding various concentrations of swine wastes for 12 days of batch cultivation. Rate constants for removing nitrates and phosphates in treating swine wastes were estimated as 0.17 (1/day) and 0.14 (1/day) in the first order reaction, respectively. 1.52(g/L) of maximum cell density was maintained at 0.20(1/day) of dilution rate in continuous culture, adding 20% swine wastes for 30 days. The chemical composition of the biomass obtained from the process showed 58.7% of protein, 11.0% of lipid and 15.6% of ash.

강원도산 참당귀와 일본산 일당귀의 생리 활성 성분 탐색

함문선,김성수,홍종수,이진하,정을권,박영식,이현용 한국미생물생명공학회 ( 구 한국산업미생물학회 ) 1996 한국미생물·생명공학회지 Vol.24 No.5

참당귀와 일당귀를 에탄올로 추출하였고 이들 추출물들을 디에틸 에테르층과 물층으로 분획하였다. 두 개의 분획물들은 Ames mutagenicity test에서 MNNG(0.5 ㎍/plate)에 대한 강한 항돌연변이 효과를 나타내었다. 디에틸 에테르 분획물들은 MNNG의 돌연변이원성을 78%에서 80%까지 억제시켜 가장 강한 돌연변이 유발 억제효과를 보여주었다. 각각의 에탄올 추출물(1㎍/㎕)들은 사람의 다양한 암세포들의 성장을 억제시켰다. 특히, 디에틸 에테르 분획물들은 간암 세포의 생육을 90%에서 95%까지 억제시켜 가장 강한 항암효과를 보여주었다. 그러나 수층 분획물들은 암세포의 생육에 대하여 거의 억제활성을 나타내지 않았다. 에탄올 추출물들은 인체의 정상 간세포에 대하여 거의 세포독성을 나타내지 않았다. 참당귀의 디에틸 에테르 분획물들은 일당귀와 비교하여 20% 미만의 세포독성을 보여주었다. 참당귀와 일당귀 디에틸 에테르 분획물들의 0.5㎍/㎕ 첨가는 T세포와 B세포의 생육의 3~4배 정도 증가에 의한 면역활성을 보여주었다. 또한 참당귀의 디에틸 에테르 분획물(0.7㎍/㎕)이 ACE 활성을 98%까지 억제시켜 혈압을 조절할 수 있음도 증명되었다. TLC로부터, 두 개의 디에틸 에테르 분획물들은 참당귀와 일당귀의 활성 성분중의 하나로 알려진 umbelliferon을 함유함을 알 수 있었다. The ethanol extracts from Anglica gigas Nakai and Angelica acutiloba Kitagawa were fractionated to diethyl ether and aqueous partitions. Both partitions had strong antimutagenic effect on the MNNG (N-methyl-N-nitro-N-nitrosoguanidine) by Ames mutagenicity of MNNG with inhibition of 78~80%. The ethanol extracts from both species showed the inhibitory effect on the growth of several human cancer cell lines. Especially, the diethyl ether fraction from ethanol extracts was most effective on human hepatocellular carcinoma cells, inhibiting 90~95% of cell growth. However, the aqueous fractions had least inhibition activity on many cancer cells. There was little cytotoxicity on human normal liver cell by ethanol extracts. Diethyl ether fraction from Angelica gigas Nakai ethanol extract had cytotoxicity les than 20% on human normal liver cells, compared with that from Angelica acutiloba Kitagawa ethanol exract. The adding of 0.5 (g/ℓ) of diethyl ether fractions of Angelica gigas Nakai or Angelica acutiloba Kitagawa increased immune activity by enhacing human B and T cells up to three to four times. It was proven that diethyl ether fraction (0.7 g/ℓ) from Angelica gigas Nakai could control blood pressure by suppressing angiotensin converting enzyme activity up to 98%. From TLC, it was appeared that both of diethyl ether partitions had umbelliferon, known to one of active substances from Angelica gigas Nakai and Angelica acutiloba Kitagawa.

혈액 투석 환자에서 중심정맥 협착에 대한 스텐트 삽입술 : Wallstent Placement

임대승,노상필,이유선,정승현,김보영,이정우,강정아,김정희,이민수,정준용,최시완,정진옥,성인환,이강욱,신영태 충남대학교 의과대학 의학연구소 2002 충남의대잡지 Vol.29 No.1

Stenosis of central vein is a common complication arising after percutaneous subclavian vein catheter insertion performed for temporary vascular access in chronic renal failure patients undergoing hemodialysis. There are several treatment methods for the condition like percutaneous angioplasty(PTA), stent insertion, and surgery, but recent trend is toward PTA and stents. Among the patients diagnosed with chronic renal failure from March 1993 to May 2002 and undergoing hemodialysis through AV fistula, the 14 Patients in whom central vein stenosis arose were selected for the study. A total of 28 percutaneous interventions(5 PTA and 23 stent placement) were performed, and restenosis rate and the time taken till the restenosis in de novo lesions and instant lesions were compared. All 28 cases were operated successfully. The 14 cases that received both anigioplasty and stent placement initially. (de novo lesion : 14 cases), Among the 10 cases with de novo lesion that followed up more than 1 year, 3 cases are currently undergoing hemodialysis without restenosis, and the remaining 7 cases have recurred stenosis with the mean time to restenosis of 10.9 months. In the 7 cases in whom stenosis recurred, 11 interventions were done(instent lesion: 11 cases). 4 of these were using only ballon angioplasty with 100% restenosis rate and the mean time of 3 months until restenosis. The remaining 7 cases were using both balloon angioplasty and stent placement, also with 100% restenosis rate but with the mean time of 12 months until restenosis, which was later than the group receiving only balloon angioplasty. In treating the patients with central vein stenosis, stent placement seems to be more advantageous over PTA in terms of restenosis rate and the mean duration of patency. In the case of instent lesion, inserting the stent for the second time after stenosis recurred lengthened the duration of patency compared to performing balloon angioplasty alone.

균질화처리한 AZ31-xCa(x=0~2.0 wt.%) 중력 주조재의 열간압연 특성

임창동,유봉선,김수현,이진수,김완철 대한금속재료학회 2004 대한금속·재료학회지 Vol.42 No.6

The effects of homogenization on hot rolling properties of gravity cast AZ31-xCa (x=0-2.0 wt.%) alloys were evaluated by examination of surfaces and microstructures of sheets. The side cracking during hot rolling was decreased by homogenization through the elimination of local inhomogeneity and solution of brittle precipitate into matrix. The coarse grains in raw materials were changed to fine grains with the average particle size of 5-10 μm by repeated hot rolling through the dynamic recrystallization. A deformation twinning was more favorably formed in the hot-rolled sheets after homogenization. It is considered that the grains grow and the precipitates are solved into the matrix during homogenization heat treatment, which results in the increased possibility of formation of deformation twinning during hot rolling. (Received March 29, 2004)