#02-오창완ok

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "#02-오창완ok"

Transcription

1 KOR J CEREBROVASCULAR SURGERY March 2OO9 Vol. 11 No 1, page 12-8 경희대학교동서신의학병원신경외과 1 서울대학교의과대학신경외과학교실분당서울대학교병원신경외과 2 방재승 1 권오기 2 오창완 2 Radiation Induced Senescence-like Changes of Endothelial Cells and Blood-brain Barrier Disruption Jae Seung Bang, MD 1, O-Ki Kwon, MD 2, Chang Wan Oh, MD 2 Department of Neurosurgery, East-West Neo Medical Center of Kyung Hee University 1 Department of Neurosurgery, Bun-dang Seoul National University Hospital, Department of Neurosurgery, Seoul National University College of Medicine 2 ABSTRACT Objectives : This study was performed to evaluate the relationship between radiation induced senescence-like changes of endothelial cells and blood-brain barrier disruption. Materials and Methods : Radiation of 15 Gy was applied to a monolayer culture of bovine aortic endothelial cells (BAEC). The morphological changes were observed over 19 weeks. An artificial blood-brain barrier (BBB) model was constructed using the Transwell and co-culture of the BAEC with C6 glioma cells. After treatment with the same dose of radiation, changes in the BBB were observed by measurement of the trans-endothelial electrical resistance (TEER). Results : Senescence-like changes of the endothelial cells appeared 1 week after irradiation; it was most prominent during the third week and replacement by normal endothelial cells was noted from the seventh week. The recovered normal endothelial monolayer was maintained until the 19th week. Senescence-like endothelial cells showed positive staining with senescence-associated β-galactosidase (SA-β-gal). In the Transwell, the TEER began to decrease 1 week after irradiation, and the decreased resistance reached its peak 18 days after irradiation, and then began to recover to some degree. Conclusion : After application of radiation (15 Gy), senescence-like changes of the endothelial cells were observed in the monolayer culture. These findings demonstrated good correlation with the disruption of blood-brain barrier in an in-vitro model of the BBB. (Kor J Cerebrovascular Surgery 11(1):12-8, 2009) KEY WORDS : Senescence Endothelial cells Radiation Blood-brain barrier. 서 론 논문접수일 : 2009 년 02 월 16 일심사완료일 : 2009 년 03 월 09 일교신저자 : 오창완, 경기도성남시분당구구미동 300 분당서울대학교병원신경외과전화 : (031) 전송 : (031) 연구비수혜사항 : 본연구논문은서울대학교병원신진연구비 ( 과제번호 ) 의일부지원으로작성되었음. 이온화방사선조사 (ionizing radiation) 는양성및악성뇌종양, 뇌혈관기형등중추신경계질환의치료에자주사용된다. 방사선조사의치료효과는조사후수미리초 (several milli-seconds) 이내에발생하는자유기 (free radical) 가염색체를파괴하여세포를사망하게함으로써이루어지는것으로여겨지고있으며, 4) 이러한기전이정상조직에도작용하여부작용을유발할수있다. 12

2 방재승 권오기 오창완 뇌및척수에대한방사선손상중일부는정상혈관손상의결과이다. 21) 이온화방사선조사는장기적으로뇌혈관협착및폐색, 뇌동맥류, 뇌괴사, 모야모야증후군, 동맥경화, 뇌출혈, 혈뇌장벽장애등을야기시킬수있으며, 22) 이러한혈관에대한영향이중추신경계방사선치료의제한요인중하나이다. 본연구에서는방사선조사후발생하는내피세포의유사-노화현상과혈뇌장벽장애의관련성에대하여실험을시행하였다. 재료및방법 1. 내피세포배양내피세포는소대동맥내피세포 (BAEC; bovine aortic endothelial cells; Cell Applications, Inc.) 를사용하였다. 동결된소대동맥내피세포를일반배양플라스크에서배양을시작하여양을늘린후, 9~21계대배양된세포를실험에사용하였다. 배양액은 DMEM/F12 배지에 10% fetal bovine serum, penicillin, streptomycin 및 fungizone을혼합하여사용하였다. 내피세포에대한방사선조사후형태학적변화를관찰하기위하여, 60 mm 페트리디쉬 (petri-dish) 에내피세포 (BAEC) 를배양하여, 세포가전체표면을모두덮은후 2일경과하여방사선을조사하였으며, 배양액은격일로교환하였다. 실험군과대조군각각 4개씩을유지하며대표적인변화소견을관찰하였다. 2. 교세포배양실험에사용할교세포는, 장기적실험을위하여배양시장기적세포생존이가능한 C6 교종세포를사용하였다. 배양에앞서배양면에대한 fibronectin 도포를시행하였고, 배양은 glutamine, penicillin, streptomycin, fungizone 등을함유한 DMEM (1.7g/L glucose) 배지를사용하였다. 3. 노화관련 senescence-associated β- galactosidase (SA-β-gal) 염색세포노화 (senescence) 감별을위하여, 거대세포로변형된내피세포에대하여 SA-β-gal 염색을시행하였다. 6) 세포를 PBS로세척후상온에서 2% formaldehyde/0.2% glutaraldehyde 용액으로 3 5분간고정한후다시 PBS로세척하였다. 이후 SA-β-gal 염색액으로핵주변세포질이확실하여질시기까지 4 5시간염색하였다. SA-β-gal 염색액은신선한것을사용하여야되며, 그성분은다음과같다 : 5- bromo-4-chloro-3-indolyl-β-d-galactoside (X-Gal) 1 mg/ml, citric acid 100 mm, sodium phosphate dibasic 200 mm, potassium ferrocyanide 5 mm, potassium ferricyanide 5 mm, NaCl 150 mm and MgCl2 2 mm; ph Transwell 혈뇌장벽모델 Costar Transwell membrane insert (polyester, 12 mm, 0.4 μm pore size) 를사용하여그상부에내피세포를 Fig. 1. Sequential changes of endothelial monolayer culture after irradiation of 15 Gy. A : Before irradiation. B : 1 week after irradiation, showing appearance of senescence-like changes. C : 3 weeks after irradiation, demonstrating prominent senescence-like cells. D : 5 weeks after irradiation, with many dead cells. E : 7 weeks after irradiation, dead cells being replaced by normal cells. F : 19 weeks after irradiation, showing typical cobble stone appearance of normal endothelial cells. Kor J Cerebrovascular Surgery 11(1):12-8,

3 배양하고하부에교세포를배양하였다. Fibronectin 도포후먼저 insert를뒤집어놓아바닥면을위로향하게하여그위에교세포를 4일간배양하여부착시켰다. 이때 insert를 100 mm 세포배양플라스크에놓고배양액이배양막까지차도록유지하였다. 교세포부착후 insert를 Transwell 에다시넣고배양막상부에내피세포를배양하여부착시켰다. 내피세포는 9계대배양된것을사용하였으며, 배양액은내피세포배양시와같은것을사용하였다. 내피세포가전체표면을모두덮은후 2일경과하여방사선을조사하였으며, 배양액은격일로교환하였다. 실험군과대조군각각 8개씩의 Transwell 을유지하였다. 5. 내피세포및 Transwell 방사선조사형태학적변화의관찰을위한페트리디쉬에배양한내피세포단막 (endothelial monolayer) 에대하여, 실험군의경우 15 Gy를조사하였고, 동일조건에서대조군을유지하였다. Transwell 의경우에서도, 실험군에는 15 Gy를조사하였고동일조건에서대조군을유지하였다. 모든경우방사선조사 24시간전에배양액을교환하였다. 6. 혈뇌장벽의검사방사선조사후혈뇌장벽의변화는경내피세포저항 (transendothelial electrical resistance; TEER) 을측정하여추정하였다. EVOM epithelial voltohmmeter (World Precision Instruments, Sarasota, Florida) 를사용하여 Transwell 상부와하부사이의저항치를측정하였으며, 상대적인변화를관찰하는것이므로표면적에따른보정은하지않았다. 정확도를높이기위하여 ENDOHM 전극 (12 mm, World Precision Instruments) 을이용하여저항을측정하였다. 7. 방사선조사후검사내피세포배양에대한방사선조사후형태학적변화는위상대조현미경 (phase contrast microscope) 을이용하여매 1 2주간격으로시행하였다. 세포의형태학적변화가뚜렷한시점에서, 실험군과대조군각 1개씩의페트리디쉬를 SA-β-gal 염색처리하여세포노화현상을확인하였다. TEER 측정은대조군과 15 Gy 방사선조사군각각 8개씩의 Transwell 에서측정하여그평균치를구하였다. 측정은방사선조사직후및이후 2 3일간격으로, 세포폐사로 TEER이급격히감소하는시점까지지속하였다. 결과 1. 방사선조사후내피세포의시간경과에따른형태변화배양 9계대내피세포를 15 Gy 방사선조사하고, 형태학적변화를위상대조현미경 (phase contrast microscope) 을이용하여관찰하였다. 방사선조사 1주후, 3주후및이후 2 주간격으로 19주까지관찰하였다. 대조군은 19주까지형태학적변화가없었다. 대조군 (Fig. 1-A) 에비하여, 실험군의경우 1주후일부세포의크기가커지는양태를보였으며 (Fig. 1-B), 3주후에는뚜렷한거대세포들이나타났다 (Fig. 1-C). 거대세포는세포핵과세포질모두그표면적의증가를보였으며, 특히세포질의양이크게증가하였다. 방사선조사 5주후에는전체적으로많은세포들이죽어가는양태를보였으나 (Fig. 1-D), 7주후부터다시건강한세포들이증식하는소견이나타나서 (Fig. 1-E) 이후 19주까지대부분의영역에서건강한세포들로대체되어있는양상을유지하였다 (Fig. 1-F). 2. 배양계대수에따른방사선조사후반응배양 9계대 (Fig. 2-A), 12계대 (Fig. 2-B) 및 21계대 (Fig. 2-C) 내피세포에 15 Gy의방사선조사후 3주경과하여형태의변화를위상대조현미경으로관찰하였다. 계대수가증가될수록방사선조사후유사-노화현상을보이는거대세포의출현이현저하게증가되는경향을보였다 (Fig. 2). Fig. 2. Effect of the number of passage on the senescence-like changes, 3 weeks after irradiation of 15 Gy. A : Passage number 9 cells. B : Passage number 12 cells. C : Passage number 21 cells. 14 Kor J Cerebrovascular Surgery 11(1): , 2009

4 방재승 권오기 오창완 3. 노화관련 SA-β-gal 염색배양 9계대내피세포를 15Gy 방사선조사하고, 3주경과하여 SA-β-gal 염색을시행하여, 거대세포의노화를검사하였다. 형태학적변화를위상대조현미경을이용하여관찰하였고 (Fig. 3-A), 동일부위의 SA-β-gal 염색소견을일반현미경으로관찰하였다 (Fig. 3-B). 거대세포대부분에서핵주변세포질의 SA-β-gal 염색양성소견이관찰되어, 이러한거대세포가노화현상을보이고있음을확인하였다 (Fig. 3- B). 4. 방사선조사후경내피세포저항의변화 Transwell 에내피세포와교세포를부착하여혈뇌장벽모델을형성한후 15 Gy 방사선을조사하고경내피세포저항 (TEER) 을 2 3일간격으로측정하였다. 대조군은방사선조사후 25일까지비교적일정한 TEER 수치를유지하다가이후급격한감소추세를보였다. 방사선조사후 7일경과하여실험군 Transwell 의 TEER이대조군에비하여감소하기시작하였으며, 이후그격차가점차증가되어 13일에는유의한차이를보였고 (p=0.04), 18일에그격차가최고에도달하였다. 이후 22일, 25일에다소격차가감소하는추세를보이다가 27일경대조군과실험군모두 TEER의감소를보이며 29 일에는급격한감소를보였다 (Fig. 4). TEER의급격한감소를보인시점에서현미경검사상대부분의세포가사망한소견이관찰되었다. 고찰 혈관의구성세포중특히내피세포는방사선에대하여취약하며, 방사선조사후급성기의여러반응에대한연구가있었다. 22) 특히, 소대동맥내피세포 (bovine aortic endothelial cells; BAEC) 를배양하여실행한실험에서이러한변화가자연적세포노화현상과유사함을관찰할수있었다. 즉, 방사선조사후계대배양 (subculture) 을하지않아 도계대배양에의해유도된자연적세포노화현상과동일한변화를관찰할수있었다. 23) 세포체의크기가증가하는형태학적변화를보였으며, 세포의표면적이방사선조사량에비례하여증가하였고, 이러한세포들은 SA-β-gal에양성반응을보여자연적노화세포와유사한생화학적특성을보였다. 이러한유사-노화세포는 p21의지속적상승을보여, 본현상이방사선조사후일시적으로나타나는세포괴사와는달리자연적세포노화 (natural cellular senescence) 와유사함을확인할수있었다. 23) 본연구에서는이러한유사-노화현상의장기적변화를관찰하기위하여, 계대배양수가적은젊은 BAEC의단층배양상태에서 15 Gy의방사선조사후 19주이상형태학적변화를관찰하였다. 계대배양수가적은젊은 BAEC를사용한이유는세포배양이비교적쉽고, 다음단계의혈뇌장벽실험시교세포와동시배양하면혈뇌장벽을잘형성하기때문이다. 12)33) 본실험결과, 내피세포의유사-노화현상은방사선조사후 1주경과하여발현되기시작하여 3 주후절정에도달하였으며, 5주경에는많은세포들이사망하는양태를보였으나 7주경에는건강한세포들이증식하여빈공간을채웠다. 이러한정상내피세포의상태는 19주까지도잘유지되었다 (Fig. 1). 방사선조사후단층배양에서발현된유사-노화현상은계대배양수가높은노화세포에서더강하게나타났으며, 이는방사선에의한유사-노화현상과자연적노화현상의유관성을시사하여주는것으로생각된다 (Fig. 2). 유사-노화현상을보인세포들은 SA-β-gal에양성염색되어, 역시생화학적으로자연적노화세포와유사한특성을보였다 (Fig. 3). 이러한유사-노화현상의발현및회복은방사선치료후혈뇌장벽장애의발생및회복경과와매우유사하다. 즉, 뇌의일반적방사선치료및정위적방사선수술후 3 12개월경과하여발생하는혈뇌장벽장애는수주 수개월지속된후회복을보이는데, 본실험의관찰결과에서도방사선조사후유사-노화현상을보이는세포들의수가 1주후부터점차증가되었다가, 이러한세포들이사라지면서 7주경부터는정상내피세포로교체되어회복되는현상이관찰되었 Fig. 3. Morphology of senescencelike endothelial cells after staining with SA-β-gal. A : Photograph by phase-contrast microscope. B : Photograph by usual microscope. Kor J Cerebrovascular Surgery 11(1):12-8,

5 다. 생체에서의변화는그시간경과가더느리게나타나지만, 이는생체외실험에서세포의변화가통상적으로더빠르게나타나는현상에기인하는것으로생각된다. 내피세포의방사선조사후관찰된유사-노화현상과뇌방사선치료후발생하는혈뇌장벽장애의관련성을확인하기위하여, BAEC와 C6 교종세포를 Transwell 에동시배양하여 인공혈뇌장벽모델 을만들어실험을시행하였다. 혈뇌장벽은혈액과중추신경간의물질교환을선택적으로조절하여주는역동적경계이며, 이러한기능은주로내피세포에서이루어지고교세포및호르몬등의영향을받는다. 1) 뇌의미세혈관내피세포는세포흡수작용 (pinocytosis) 이적고천공 (fenestration) 이없으며세포외물질투과를막는폐쇄소대 (tight junction) 가있다. 1) 생화학적으로는특이한선택적물질이동기전과관련된 gamma-glutamyltranspeptidase, glucose transporter type 1 (GLUT-1), P-glycoprotein, alkaline phosphatase, Na + -K + -ATPase, Ca ++ -ATPase, and 5 -nucleotidase 등의표식자가특징적으로나타난다. 25) 이러한혈뇌장벽표식자는뇌혈관및비-뇌혈관내피세포모두에서발현될수있으며, 25)35) 교세포의세포막구조물혹은용해성분비물이내피세포에작용하여이러한혈뇌장벽특성을유도하는것으로추정된다. 1)30) 따라서실험실에서 인공혈뇌장벽모델 을만들기위해서는내피세포와교세포의동시배양이필요하며, 이러한목적으로가장간단한것은 Transwell 을사용하여, 배양막의상부에는내피세포를하부에는교세포를배양하는것이며, 본실험에서는이러한모델을사용하였다. 방사선조사후혈뇌장벽의변화는배양막상부와하부간의경내피세포저항 (trans-endothelial electrical resistance; TEER) 을측정하여추정하였 Fig. 4. Changes of trans-endothelial electrical resistance (TEER) after irradiation. Endo : Endothelial Cell. Astro : Astrocyte (C6 glioma cell). 다. 9)11)12)16) 실험결과, 방사선조사후 1주경과하여실험군의혈뇌장벽장애가관찰되기시작하였으며, 18일경장애가절정에도달하였고, 이후다소회복을보이는추세를보였다 (Fig. 4). Transwell 의경우배양세포의생존기간이상대적으로짧아, 방사선조사 4주경과하여대부분의세포들이사망하여좀더장기적인변화를관찰할수는없었다. 그러나관찰기간중내피세포의단층배양에서의유사-노화현상발현과유사한경과를보이는혈뇌장벽장애의발생을확인할수있었다. 방사선이교세포에미치는영향이혈뇌장벽장애에기여할가능성도있으나, 방사선조사후동물교세포의조직학적변화는미미하고, 17) 본연구자의예비실험에서도동일량의방사선조사후교세포는내피세포에비해큰변화를보이지않아그기여도는적을것으로추정되며, 이러한혈뇌장벽장애발생의주원인은내피세포의변화일것으로추정된다. 본연구의결과는, 방사선조사후관찰되는배양된내피세포의유사-노화현상이방사선치료후발생하는일과적혈뇌장벽장애와관련성이있음을시사하고있다. 세포노화현상 (cellular senescence) 이란생체노화현상 (aging) 과대비된생체외배양세포의노화현상을지칭한다. 10)15)27) 노화세포 (senescent cell) 는영구적으로세포분열능력이없으며, 특징적인세포기능변화를보인다. 24)29) 생화학적으로는 telomere의단축, 8) telomerase의억제, 29) 산화성 DNA 손상, 5) 각종종양억제유전자 (p53, prb, p16 INK4a and p21 WAF1 ) 의발현 2)28)34)36) 및발암유전자 (proto-oncogenes) 의이상발 현 13)31) 등이나타난다. 노화세포와단순히분열을멈춘세포 (quiescent cell) 를감별할수있는표식자로는 SA-β-gal, 6) 변형된 fibronectin 발현, 14) interleukin-1α 7) 등이있다. 한편, 방사선조사된세포중세포분열능력을상실한세포 (clonologically dead cells) 들은특징적으로노화세포와유사한형태로변화되며, 이러한세포중일부는노화세포에특이하게반응하는항체에대해서도양성반응을보이는것으로알려져있다. 26) Bey-Dih 등 3) 은방사선및항암제로처치한종양세포가노화세포와유사한특징을보이며, 노화세포표식자인 SA-β-gal에반응하고영구적으로분열이불가능한것으로보고하였다. 이러한현상은방사선에의한염색체의영구적손상이, 반복세포분열에의한 telomere 손실이유발하는자연적세포노화 (natural senescence) 현상과유사한작용을하는것으로설명할수있다. 이러한방사선조사세포들은염색체손상으로세포분열능력은잃었으나상당기간생존이가능한것으로알려져있다. 본연구에서도배양중인내포세포에방사선조사후유사-노화세포가생성되며, 이러한세포들이정상내피세포로교체되기까지수주간생존하는것을확인할수있었다. 한편, 노화된동물은혈뇌장벽의변 16 Kor J Cerebrovascular Surgery 11(1):12-8, 2009

6 방재승 권오기 오창완 화를보여선택적투과성이상실되며특히 choline, 18) glucose, 20) triiodothyronine 19) 등에대하여그러하다. 인간태정맥내피세포 (human umbilical vein endothelial cell; HUVEC) 를이용한실험에서내피세포노화는여러유전자발현의변화를보였으며, 이들중일부는혈관기능과중요한관련이있을것으로추정된다. 32) 본연구의결과는, 방사선조사로유발된내피세포의유사-노화현상역시혈뇌장벽의장애발생과관련이있음을시사하고있으며, 이는자연적노화에서관찰되는혈뇌장벽장애현상과유사성이있다. 결 배양된내피세포에방사선조사후장기간관찰한결과일시적으로유사-노화세포들이발생하며, 이러한세포들은수주간생존하였다가점차정상세포로대체되어회복되는것을관찰할수있었다. 이러한내피세포의변화는방사선조사후발생하는일과성혈뇌장벽장애와관련성이있을것으로사료된다. 론 중심단어 : 세포노화 내피세포 방사선조사 혈뇌장벽. REFERENCES 11) Abbott NJ, Revest PA. Control of brain endothelial permeability. Cerebrovasc Brain Metab Rev 3:39-72, ) Atadja P, Wong H, Garkavtsev I, Veillette C, Riabowol K. Increased activity of p53 in senescing fibroblasts. Proc Natl Acad Sci USA 92: , ) Chang BD, Broude EV, Dokmanovic M, Zhu H, Ruth A, Xusan Y, et al. A senescence-like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents. Cancer Res 59:3761-7, ) Bump EA, Malaker K. Radioprotectors:Chemical, Biological and Clinical Perspectives. BocaRaton, CRCPress, 1998, pp ) Chen Q, Fischer A, Reagan JD, Yan LJ, Ames BN. Oxidative DNA damage and senescence of human diploid fibroblast cells. Proc Natl Acad Sci USA 92: , ) Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad USA 92:9363-7, ) Garfinkel S, Brown S, Wessendorf JHM, Maciag T. Posttranscriptional regulation of interleukin 1 alpha in various strains of young and senescent human umbilical vein endothelial cells. Proc Natl Acad Sci USA 91: , ) Harley CB, Futcher AB, Greider CW. Telomeres shorten during aging of human fibroblasts. Nature 345:458-60, ) Hayashi Y, Nomura M, Yamagishi S, Harada S, Yamashita J, Yamamoto H. Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes. Glia 19:13-26, ) Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res 25: , ) Hurst RD, Clark JB. Alterations in transendothelial electrical resistance by vasoactive agonists and cyclic AMP in a blood-brain barrier model system. Neurochem Res 23:149-54, ) Isobe I, Watanabe T, Yotsuyanagi T, Hazemoto N, Yamagata K, Ueki T, et al. Astrocytic contributions to blood-brain barrier (BBB) formation by endothelial cells:a possible use of aortic endothelial cells for in vitro BBB model. Neurochem Int 28:523-33, ) Lee AC, Fenster BE, Ito H, Takeda K, Bae NS, Hirai T, et al. Ras proteins induce senescence by altering the intracellular levels of reactive oxygen species. J Biol Chem 274: , ) Magnuson VL, Young M, Schattenberg DG, Mancini MA, Chen DL, Steffensen B, et al. The alternative splicing of fibronectin premrna is altered during aging and in response to growth factors. J Biol Chem 266: , ) Martin GM, Sprague CA, Epstein CJ. Replicative life-span of cultivated human cells. Lab Invest 23:86-92, ) McCarthy KD, de Vellis J. Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissues. J Cell Biol 85: , ) Mildenberger M, Beach TG, McGeer EG, Ludgate CM. An animal model of prophylactic cranial irradiation:histological effects at acute, early and delayed stages. Int J Radiat Oncol Biol Phys 18: , ) Mooradian AD. Blood-brain barrier transport of choline is reduced in aged rats. Brain Res 440:328-32, ) Mooradian AD. Blood-brain transport of triiodothyronine is reduced in aged rats. Mech Aging Dev 52:141-7, ) Mooradian AD, Morin AM, Cipp LJ, Haspel HC. Glucose transport is reduced in the blood-brain barrier of aged rats. Brain Res 551:145-9, ) Munter MW, Karger CP, Reith W, Schneider HM, Peschke P, Debus J. Delayed vascular injury after single high-dose irradiation in the rat brain:histologic, immunohistochemical, and angiographic studies. Radiology 212:475-82, ) O Connor MM, Mayberg MR. Effects of radiation on cerebral vasculature:a review. Neurosurgery 46:138-49, ) Oh CW, Bump EA, Kim JS, Janigro D, Mayberg MR. Induction of a senescence-like phenotype in bovine aortic endothelial cells by ionizing radiation. Radiat Res 156:232-40, ) Oshimura M, Barrett JC. Multiple pathways to cellular senescence:role of telomerase repressors. Eur J Cancer 33:710-5, ) Partridge WM, Boado RJ. Blood-Brain Barrier:Cellular and Molecular Biology. NewYork, Raven Press, 1993, pp ) Porter MB, Pereira-Smith OM, Smith JR. Common senescent cellspecific antibody epitopes on fibronectin in species and cells of varied origin. J Cell Physiol 150:545-51, ) Rohme D. Evidence for a relationship between longevity of mammalian species and life spans of normal fibroblasts in vitro and erythrocytes in vivo. Proc Natl Acad USA 78: , ) Sandhu C, Peehl DM. Slingerland J. p16ink4a mediates cyclin dependent kinase 4 and 6 inhibition in senescent prostatic epithelial cells. Cancer Res 60: , ) Sasaki M, Honda T, Yamada H, Wake N, Barrett JC, Oshimura M. Evidence for multiple pathways to cellular senescence. Cancer Res 54:6090-3, ) Saunders NR, Dziegielewska KM. Barriers in the developing brain. News Physiol Sci 12:22-31, ) Seshadri T, Campisi J. Repression of c-fos transcription and an altered genetic program in senescent human fibroblasts. Science 247:205-9, ) Shelton DN, Chang E, Whittier PS, Choi D, Funk WD. Microarray Kor J Cerebrovascular Surgery 11(1):12-8,

7 analysis of replicative senescence. Curr Biol 9:939-45, ) Stanness KA, Westrum LE, Fornaciari E, Mascagni P, Nelson JA, Stenglein SG, et al. Morphological and functional characterization of an in vitro blood-brain barrier model. Brain Res 771:329-42, ) Stein GH, Drullinger LF, Soulard A, Dulic V. Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. Mol Cell Biol 19: , ) Tao-Cheng J, Nagy Z, Brightman MW. Tight junctions of brain endothelium in vitro are enhanced by astroglia. J Neurosci 7:3293-9, ) Vogt M, Haggblom C, Yeargin J, Christiansen-Weber T, Haas M. Independent induction of senescence by p16ink4a and p21cip1 in spontaneously immortalized human fibroblasts. Cell Growth Differ 9:139-46, Kor J Cerebrovascular Surgery 11(1):12-8, 2009

노인의학200303.PDF

노인의학200303.PDF 2 1. 2. 1) 2) 3) 3. 4. 1) 2) 3) Microcell 4) 5) 5. 6. 1.. (organism).,...?,??.,. 1935 McCay 27 . 1960 Hayflick. 10 (cytogerontology)... 2. 1),,,,.,,,.. (lipofuscin) (fluidity),., (microvilli)..,, (heat

More information

γ

γ 경락경혈학회지 Vol.27, No.1, pp.87 106, 2010 Journal of Meridian & Acupoint Dept. of 1 Meridian & Acupoint, 3 Acupuncture & Moxibustion, College of Oriental Medicine, Daejeon University 2 Division of Clinical

More information

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee University College of Medicine & Hospital E mail : ycell2@yahoo.co.kr Abstract

More information

( )Kju269.hwp

( )Kju269.hwp 만성세균성전립선염모델흰쥐에서 의항염효과 Anti-inflammatory Effect of Lycopene on Chronic Bacterial Prostatitis Rat Model Cho Hwan Yang, Dong Wan Sohn, Yong-Hyun Cho From the Department of Urology, The Catholic University

More information

(01) hwp

(01) hwp Journal of Life Science 2013 Vol. 23. No. 2. 157~166 ISSN (Print) 1225-9918 ISSN (Online) 2287-3406 DOI : http://dx.doi.org/10.5352/jls.2013.23.2.157 α μ δ κ 158 생명과학회지 2013, Vol. 23. No. 2 Journal of

More information

Jksvs019(8-15).hwp

Jksvs019(8-15).hwp Grade I Grade II Grade III 12 대한혈관외과학회지 : 제 20 권 제 1 호 2004 Control Group A Group B Fig. 4. Microscopic findings of vein wall in control, group A and group B on the day of 7 after venous occlusion. The

More information

A 617

A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R

More information

달생산이 초산모 분만시간에 미치는 영향 Ⅰ. 서 론 Ⅱ. 연구대상 및 방법 達 은 23) 의 丹 溪 에 최초로 기 재된 처방으로, 에 복용하면 한 다하여 난산의 예방과 및, 등에 널리 활용되어 왔다. 達 은 이 毒 하고 는 甘 苦 하여 氣, 氣 寬,, 結 의 효능이 있

달생산이 초산모 분만시간에 미치는 영향 Ⅰ. 서 론 Ⅱ. 연구대상 및 방법 達 은 23) 의 丹 溪 에 최초로 기 재된 처방으로, 에 복용하면 한 다하여 난산의 예방과 및, 등에 널리 활용되어 왔다. 達 은 이 毒 하고 는 甘 苦 하여 氣, 氣 寬,, 結 의 효능이 있 대한한방부인과학회지 THE JOURNAL OF ORIENTAL OBSTETRICS & GYNECOLOGY VOL.17, NO.2 : 115-122 (2004) 달생산이 초산모 분만시간에 미치는 영향 * 북경한의원, ** 윤산부인과의원, *** 최은림산부인과의원, 상지대학교 한의과대학 부인과학교실 ****, 경희대학교 동서의학대학원 김성준 *****, 윤왕준

More information

Can032.hwp

Can032.hwp Chromosomal Alterations in Hepatocellular Carcinoma Cell Lines Detected by Comparative Genomic Hybridization Sang Jin Park 1, Mahn Joon Ha, Ph.D. 1, Hugh Chul Kim, M.D. 2 and Hyon Ju Kim, M.D. 1 1 Laboratory

More information

( )Jkstro011.hwp

( )Jkstro011.hwp 비인강암의방사선치료결과및생존율에관한예후인자분석 2005 2 1 2005 3 28. :, Tel: 053)250-7665, Fax: 053)250-7984 E-mail: jhkim@dsmc.or.kr 정영연외 2 인 : 비인강암의예후인자분석 정영연외 2 인 : 비인강암의예후인자분석 Carcinoma of the nasopharynx treated by radiotherapy

More information

(

( 317 318 319 320 1 3 5 5 5 5 2 321 : 1.,,,,, 06 2. X-ray beam penetration (density) (contrast) 03 3. patch coating, precipitation, flaking 03 4. centering 03 5. Esophagus, cardia, fundus, body, angle, antrum,

More information

A Study on the Relationships between Self-Differentiation and Adaptability Factors for Senior Dementia Patients Care Givers Department of Social Welfare, Seoul Welfare Graduate University Full-time Lecturer

More information

Lumbar spine

Lumbar spine Lumbar spine CT 32 111 DOI : 10.3831/KPI.2010.13.2.111 Lumbar Spine CT 32 Received : 10. 05. 23 Revised : 10. 06. 04 Accepted : 10. 06. 11 Key Words: Disc herniation, CT scan, Clinical analysis The Clinical

More information

02-³í´Ü1

02-³í´Ü1 Molecular and Cellular Biology News 1 Molecular and Cellular Biology News 4 2010 2 Molecular and Cellular Biology News 3 Molecular and Cellular Biology News 4 2010 4 Molecular and Cellular Biology News

More information

Jkbcs016(92-97).hwp

Jkbcs016(92-97).hwp Expression of bcl-2 and Apoptosis and Its Relationship to Clinicopathological Prognostic Factors in Breast Cancer - A Study with Long Term Follow-up correlated with the survival rate.(journal of Korean

More information

1..

1.. Volume 12, Number 1, 6~16, Factors influencing consultation time and waiting time of ambulatory patients in a tertiary teaching hospital Jee-In Hwang College of Nursing Science, Kyung Hee University :

More information

- i - - ii - - iii - - iv - - v - - 1 - - 2 - - 3 - - 4 - - 5 - - 6 - - 7 - - 8 - - 9 - - 10 - - 11 - - 12 - - 13 - - 14 - - 15 - - 16 - - 17 - - 18 - - 19 - α α - 20 - α α α α α α - 21 - - 22 - - 23 -

More information

Journal of Educational Innovation Research 2017, Vol. 27, No. 1, pp DOI: * The

Journal of Educational Innovation Research 2017, Vol. 27, No. 1, pp DOI:   * The Journal of Educational Innovation Research 2017, Vol. 27, No. 1, pp.243-268 DOI: http://dx.doi.org/10.21024/pnuedi.27.1.201703.243 * - 2001 2015 - The Research Trends on Peer Counseling in Elementary and

More information

Crt114( ).hwp

Crt114( ).hwp cdna Microarray Experiment: Design Issues in Early Stage and the Need of Normalization Byung Soo Kim, Ph.D. 1, Sunho Lee, Ph.D. 2, Sun Young Rha, M.D., Ph.D. 3,4 and Hyun Cheol Chung, M.D., Ph.D. 3,4 1

More information

DBPIA-NURIMEDIA

DBPIA-NURIMEDIA The e-business Studies Volume 17, Number 6, December, 30, 2016:237~251 Received: 2016/11/20, Accepted: 2016/12/24 Revised: 2016/12/21, Published: 2016/12/30 [ABSTRACT] Recently, there is an increasing

More information

Jkbcs032.hwp

Jkbcs032.hwp Clinical Correlation of HER-2/neu Overexpression in Patients with Breast Cancer Sung Yong Kim, Tae Yoon Kim, Jae Jun Kim, Chang Ho Kim, Ok Pyung Song, Min Hyuk Lee, Eui Han Kim 1, and Moo Sik Cho Departments

More information

- i - - ii - - iii - - iv - - v - - vi - - 1 - - 2 - - 3 - 1) 통계청고시제 2010-150 호 (2010.7.6 개정, 2011.1.1 시행 ) - 4 - 요양급여의적용기준및방법에관한세부사항에따른골밀도검사기준 (2007 년 11 월 1 일시행 ) - 5 - - 6 - - 7 - - 8 - - 9 - - 10 -

More information

09-감마선(dh)

09-감마선(dh) Journal of Radiation Industry 4 (3) : 253~257 (2010) Review Paper 감마선 조사가 포인세티아의 발근, 생육 및 색상변이에 미치는 영향 이은경* 김원희 김성태 강시용 1 국립원예특작과학원, 1 한국원자력연구원 Rooting, Growth, and Color Mutation of Poinsettias Affected

More information

서강대학교 기초과학연구소대학중점연구소 심포지엄기초과학연구소

서강대학교 기초과학연구소대학중점연구소 심포지엄기초과학연구소 2012 년도기초과학연구소 대학중점연구소심포지엄 마이크로파센서를이용한 혈당측정연구 일시 : 2012 년 3 월 20 일 ( 화 ) 14:00~17:30 장소 : 서강대학교과학관 1010 호 주최 : 서강대학교기초과학연구소 Contents Program of Symposium 2 Non-invasive in vitro sensing of D-glucose in

More information

4 5 6 7 8 9 10 11 12 13 14 15 조 희 영 선 생 님 고 맙 습 니 다 16 17 18 19 가정간호 장선미 간호사님 감사합니다 20 21 22 23 24 25 U l 26 27 p SEOUL MEDICAL CENTER NEWS 28 29 30 31 32 33 34 35 36 37 홍보실장이란 신동규 원고를 기다립니다

More information

2009;21(1): (1777) 49 (1800 ),.,,.,, ( ) ( ) 1782., ( ). ( ) 1,... 2,3,4,5.,,, ( ), ( ),. 6,,, ( ), ( ),....,.. (, ) (, )

2009;21(1): (1777) 49 (1800 ),.,,.,, ( ) ( ) 1782., ( ). ( ) 1,... 2,3,4,5.,,, ( ), ( ),. 6,,, ( ), ( ),....,.. (, ) (, ) Abstract Kim Dal-Rae, Kim Sun-Hyung* Dept. of Sasang Constitutional Medicine, College of Oriental Medicine, Kyung-Hee Univ. *Dept. of Sasang Constitutional Medicine, East-West Neo Medical Center, Kyung-Hee

More information

: C, Y, =0, (Crook et al.(2007) ) ( ) 1 2 3 4 5 966 967 967 967 967 4,834 234 383 462 516 508 2,103 (A) 1 661 1,629 2,623 3,802 7,613 3,806 1,040 1,636 2,175 2,788 4,193 2,629 (B) 2,128 2,676 3,492

More information

α α α α α

α α α α α α α α α α α α α 太陰調胃湯加減方 dbdb 마우스 肝에 대한 아디포사이토카인 및 발현에 미치는 영향 SREBPs 와 섞어서 하고 마커 또한 하여 전기 영동을 하였다 전기영동을 한 후에 에 를 쪼여서 각 를 확인하였다 이 를 프로그램을 이용해 수치화하 여 분석하였다 肝 조직 동결 절편 분리한 조직은 로 시간 동안 고정 시킨 후 에 세척한 후 물기를

More information

<283732372D3733312920B4D9C3CAC1A120BCD2C7C1C6AEC4DCC5C3C6AEB7BBC1EEC0C720B3EBBEC8C0C720BDC3B7C2BAB8C1A4BFA120B4EBC7D120C0AFBFEBBCBA20C6F2B0A1283035292E687770>

<283732372D3733312920B4D9C3CAC1A120BCD2C7C1C6AEC4DCC5C3C6AEB7BBC1EEC0C720B3EBBEC8C0C720BDC3B7C2BAB8C1A4BFA120B4EBC7D120C0AFBFEBBCBA20C6F2B0A1283035292E687770> 대한안과학회지 제 49 권 제 5 호 2008 J Korean Ophthalmol Soc 49(5):727-731, 2008 DOI : 10.3341/jkos.2008.49.5.727 다초점 소프트콘택트렌즈의 노안의 시력보정에 대한 유용성 평가 김현경 1 김효명 2 정성근 1 가톨릭대학교 의과대학 성모병원 안과학교실 1, 고려대학교 의과대학 안암병원 안과학교실

More information

Microsoft PowerPoint - 김미영

Microsoft PowerPoint - 김미영 암세포의위험한여행 한국과학기술원 김미영 강의개요 전이란무엇인가? 전이는어떤과정을통해진행될까? 전이예측방법은어떤것들이있을까? Cancer ( 악성종양 ) US South Korea 질병사망률질병사망률 1. 심장병 26% 1. Cancer 26.7% 2. Cancer 23% 2. 뇌출혈 12.7% 3. 뇌출혈 5.6% 3. 심장병 7.9% >20,000 환자가악성종양에의해매일사망함

More information

44-4대지.07이영희532~

44-4대지.07이영희532~ A Spatial Location Analysis of the First Shops of Foodservice Franchise in Seoul Metropolitan City Younghee Lee* 1 1 (R) 0 16 1 15 64 1 Abstract The foodservice franchise is preferred by the founders who

More information

untitled

untitled 3. 농업환경연구과 과제구분 기본연구 수행시기 전반기 연구과제 및 세부과제 수행 기간 소 속 책임자 농가에 적합한 부식성곤충 대량 사육기술 개발 12~ 13 농업환경연구과 곤충팀 이영혜 1) 부식성 곤충 먹이 제조 기술 개발 12~ 13 농업환경연구과 곤충팀 이영혜 색인용어 부식성곤충, 장수풍뎅이, 계통, 먹이제조 ABSTRACT In first check,

More information

386-390.hwp

386-390.hwp 386 HANYANG MEDICAL REVIEWS Vol. 29 No. 4, 2009 우리나라 미숙아의 통계와 의료비용 Statistics and Medical Cost of Preterm in Korea 윤혜선 을지대학교 노원을지병원 소아청소년과학교실 Hye Sun Yoon, M.D., Ph.D., Department of Pediatrics, Nowon

More information

Sheu HM, et al., British J Dermatol 1997; 136: Kao JS, et al., J Invest Dermatol 2003; 120:

Sheu HM, et al., British J Dermatol 1997; 136: Kao JS, et al., J Invest Dermatol 2003; 120: Sheu HM, et al., British J Dermatol 1997; 136:884-890 Kao JS, et al., J Invest Dermatol 03; 1:446-464 1 10 0 3 Day Normal MLE Lotion Lotion MLE Cream Cream 80 7 70 6 3 Day Normal MLE Lotion Lotion MLE

More information

±èÇ¥³â

±èÇ¥³â 533 Fig. 1. Dead zone. Nine echoes are positioned 2-10 mm below the scan surface with 1 mm distance. All nine echoes are clearly visualized. 534 Fig. 2. Vertical and horizontal measurement. 10 cm distance

More information

:,,.,. 456, 253 ( 89, 164 ), 203 ( 44, 159 ). Cronbach α= ,.,,..,,,.,. :,, ( )

:,,.,. 456, 253 ( 89, 164 ), 203 ( 44, 159 ). Cronbach α= ,.,,..,,,.,. :,, ( ) :,,.,. 456, 253 ( 89, 164 ), 203 ( 44, 159 ). Cronbach α=.83.91.,.,,..,,,.,. :,, (402-751) 253 E-mail : yspark@inha.ac.kr ..,.,.,. Bandura(1997),.,,,,., (,,, 2009), (,,,, 2014).?.,,,.. Bandura (1995) (Resiliency

More information

01 Buffers & Gel Stain Buffers 3 Gel Stain SilverStar Staining Kit 6

01 Buffers & Gel Stain Buffers 3 Gel Stain SilverStar Staining Kit 6 Buffers & Gel Stain Chemicals Buffers & Chemicals Phone: 1588-9788 (ext.4->2) Email: reagents-support@bioneer.co.kr 01 Buffers & Gel Stain Buffers 3 Gel Stain SilverStar Staining Kit 6 Buffers Overview

More information

2016 학년도약학대학면접문제해설 문제 2 아래의질문에 3-4분이내로답하시오. 표피성장인자수용체 (epidermal growth factor receptor, EGFR) 는수용체티로신인산화효소군 (receptor tyrosine kinases, RTKs) 의일종으로서세

2016 학년도약학대학면접문제해설 문제 2 아래의질문에 3-4분이내로답하시오. 표피성장인자수용체 (epidermal growth factor receptor, EGFR) 는수용체티로신인산화효소군 (receptor tyrosine kinases, RTKs) 의일종으로서세 본문제에대한지적소유권은동국대학교에있습니다. 본교의서면허락없이무단으로출판, 게재, 사용할수없습니다. 문제 2 2016 학년도약학대학면접문제 아래의질문에 3-4 분이내로답하시오. 표피성장인자수용체 (epidermal growth factor receptor, EGFR) 는수용체티로신 인산화효소군 (receptor tyrosine kinases, RTKs) 의일종으로서세포의생존과증식

More information

DBPIA-NURIMEDIA

DBPIA-NURIMEDIA The e-business Studies Volume 17, Number 4, August, 30, 2016:319~332 Received: 2016/07/28, Accepted: 2016/08/28 Revised: 2016/08/27, Published: 2016/08/30 [ABSTRACT] This paper examined what determina

More information

°ø±â¾Ð±â±â

°ø±â¾Ð±â±â 20, 30, 40 20, 30, 40 1 2 3 4 5 6 7 8 9 10 3.1 6.3 9.4 12.6 15.7 18.8 22.0 25.1 28.3 31.4 2.4 4.7 7.1 9.4 11.8 14.1 16.5 18.8 21.2 23.6 7.1 14.1 21.2 28.3 35.3 42.4 49.5 56.5 63.6 70.7 5.9 11.9 17.8 23.7

More information

석사논문.PDF

석사논문.PDF ABO Rh A study on the importance of ABO and Rh blood groups information in Public Health 2000 2 1 ABO Rh A study on the importance of ABO and Rh blood groups information in Public Health 2000 2 2 ABO Rh

More information

878 Yu Kim, Dongjae Kim 지막 용량수준까지도 멈춤 규칙이 만족되지 않아 시행이 종료되지 않는 경우에는 MTD의 추정이 불가 능하다는 단점이 있다. 최근 이 SM방법의 단점을 보완하기 위해 O Quigley 등 (1990)이 제안한 CRM(Continu

878 Yu Kim, Dongjae Kim 지막 용량수준까지도 멈춤 규칙이 만족되지 않아 시행이 종료되지 않는 경우에는 MTD의 추정이 불가 능하다는 단점이 있다. 최근 이 SM방법의 단점을 보완하기 위해 O Quigley 등 (1990)이 제안한 CRM(Continu 한 국 통 계 학 회 논 문 집 2012, 19권, 6호, 877 884 DOI: http://dx.doi.org/10.5351/ckss.2012.19.6.877 Maximum Tolerated Dose Estimation Applied Biased Coin Design in a Phase Ⅰ Clinical Trial Yu Kim a, Dongjae Kim

More information

<30382EC0C7C7D0B0ADC1C22E687770>

<30382EC0C7C7D0B0ADC1C22E687770> 대한내과학회지: 제 76 권 제 2 호 2009 의학강좌-개원의를 위한 모범처방(Current Clinical Practice) 간기능검사의 이해와 적용 인제대학교 의과대학 일산백병원 내과학교실 김 경 아 Understanding and application of liver function tests Kyung-Ah Kim, M.D. Department of

More information

(......).hwp

(......).hwp 7 6 4 10 20 30 ph 5 4 3 0 10 20 30 40 50 60 Fermentation time(day) Fig.2-1. Changes of ph in DLMK according to various fermentation temperature 2 4 10 20 30 Acidity (%) 1 0 0 10 20 30 40 50 60 Fermentation

More information

-07-......

-07-...... A Depth Interview on Qualification, Role, and Professionalism of Infant/Toddler Teachers Department of Child & Family Studies, Kyung Hee University Associate Professor : Ahn, Sun Hee Department of Early

More information

Journal of Educational Innovation Research 2018, Vol. 28, No. 4, pp DOI: 3 * The Effect of H

Journal of Educational Innovation Research 2018, Vol. 28, No. 4, pp DOI:   3 * The Effect of H Journal of Educational Innovation Research 2018, Vol. 28, No. 4, pp.577-601 DOI: http://dx.doi.org/10.21024/pnuedi.28.4.201812.577 3 * The Effect of Home-based Activities Using Traditional Fairy Tales

More information

A Study on Married Female Immigrants Life Style and Marriage Satisfaction in Terms of Preparing Their Old Age in Chungcheongnam-do Department of Gerontology, Hoseo University Doctoral Student : Hi Ran

More information

03이경미(237~248)ok

03이경미(237~248)ok The recent (2001-2010) changes on temperature and precipitation related to normals (1971-2000) in Korea* Kyoungmi Lee** Hee-Jeong Baek*** ChunHo Cho**** Won-Tae Kwon*****. 61 (1971~2000) 10 (2001~2010).

More information

<352EC7E3C5C2BFB55FB1B3C5EBB5A5C0CCC5CD5FC0DABFACB0FAC7D0B4EBC7D02E687770>

<352EC7E3C5C2BFB55FB1B3C5EBB5A5C0CCC5CD5FC0DABFACB0FAC7D0B4EBC7D02E687770> 자연과학연구 제27권 Bulletin of the Natural Sciences Vol. 27. 2013.12.(33-44) 교통DB를 이용한 교통정책 발굴을 위한 통계분석 시스템 설계 및 활용 Statistical analytic system design and utilization for transport policy excavation by transport

More information

Kbcs002.hwp

Kbcs002.hwp Does Real-time Compound Imaging Improve Evaluation of reast Cancer Compared to Conventional Sonography? o Kyoung Seo, M.D., Yu Whan Oh, M.D., Kyu Ran Cho, M.D., Young Hen Lee, M.D., Hyung Joon Noh, M.D.,

More information

아태연구(송석원)13-2-05.hwp

아태연구(송석원)13-2-05.hwp 아태연구 제 13권 제 2호 2006년 11월 30일 pp.81~103 일본에서의 한국학연구 - 회고와 전망 宋 錫 源 경희대학교 사회과학부 정치외교학과 조교수 Ⅰ. 머리말 Ⅱ. 1945년 이전의 한국연구 Ⅲ. 1945년 이후의 한국연구 < 목 차 > Ⅳ. 맺음말 참고문헌 Abstract Key words(중심용어): 한국학(Korean studies), 식민지지배(colonial

More information

54 한국교육문제연구제 27 권 2 호, I. 1.,,,,,,, (, 1998). 14.2% 16.2% (, ), OECD (, ) % (, )., 2, 3. 3

54 한국교육문제연구제 27 권 2 호, I. 1.,,,,,,, (, 1998). 14.2% 16.2% (, ), OECD (, ) % (, )., 2, 3. 3 27 2, 53-70, 2009. (Nursing Home) * ** (Nursing Home). 5 50 5 2 1,,,,, SPSS t.,,,,,,,. :,, : 2009/08/27 : 2009/09/24 : 2009/09/30 * ** (: hjkim@daelim.ac.kr) 54 한국교육문제연구제 27 권 2 호, 2009. I. 1.,,,,,,, (,

More information

Microsoft Word - KSR2016S168

Microsoft Word - KSR2016S168 2016 년도 한국철도학회 춘계학술대회 논문집 KSR2016S168 GPR 을 이용한 자갈궤도 파울링층 파악을 위한 실내실험적 접근 Evaluation of Applicability of GPR to Detect Fouled Layer in Ballast Using Laboratory Tests 신지훈 *, 최영태 **, 장승엽 *** Ji-hoon. Shin

More information

DBPIA-NURIMEDIA

DBPIA-NURIMEDIA The e-business Studies Volume 17, Number 6, December, 30, 2016:3~20 Received: 2016/12/04, Accepted: 2016/12/27 Revised: 2016/12/27, Published: 2016/12/30 [ABSTRACT] This study aims to comprehensively analyze

More information

Journal of Educational Innovation Research 2018, Vol. 28, No. 4, pp DOI: * A Research Trend

Journal of Educational Innovation Research 2018, Vol. 28, No. 4, pp DOI:   * A Research Trend Journal of Educational Innovation Research 2018, Vol. 28, No. 4, pp.295-318 DOI: http://dx.doi.org/10.21024/pnuedi.28.4.201812.295 * A Research Trend on the Studies related to Parents of Adults with Disabilities

More information

김범수

김범수 Analysis of Outcomes after Resection of Sarcomatous Hepatocellular Carcinoma Purpose: Sarcomatous hepatocellular carcinoma (HCC) is rare. Therefore, the clinicopathologic characteristics and prognosis

More information

DBPIA-NURIMEDIA

DBPIA-NURIMEDIA e- 비즈니스연구 (The e-business Studies) Volume 17, Number 1, February, 28, 2016:pp. 293~316 ISSN 1229-9936 (Print), ISSN 2466-1716 (Online) 원고접수일심사 ( 수정 ) 게재확정일 2015. 12. 04 2015. 12. 24 2016. 02. 25 ABSTRACT

More information

388 The Korean Journal of Hepatology : Vol. 6. No COMMENT 1. (dysplastic nodule) (adenomatous hyperplasia, AH), (macroregenerative nodule, MR

388 The Korean Journal of Hepatology : Vol. 6. No COMMENT 1. (dysplastic nodule) (adenomatous hyperplasia, AH), (macroregenerative nodule, MR 6 3 2000 ; 387-392 (3) Dysplastic Nodule Young Nyun Park, M.D., Chanil Park, M.D. Department of Pathology, Yonsei University College of Medicine BRIEF HISTORY 56. AST/ALT 72/73 IU/L, total bilirubin 0.7

More information

untitled

untitled 대한수혈학회지:제권 제호, 0 한 대학병원의 혈액 폐기 분석 김병철ㆍ서영익ㆍ채금란ㆍ신정원ㆍ최태윤 = Abstract = 순천향대학교 의과대학 서울병원 진단검사의학교실 Analysis of Discarded Blood Components at a University Hospital in Korea Byung Chul Kim, Young Ik Seo, Gum Ran

More information

27 2, 17-31, , * ** ***,. K 1 2 2,.,,,.,.,.,,.,. :,,, : 2009/08/19 : 2009/09/09 : 2009/09/30 * 2007 ** *** ( :

27 2, 17-31, , * ** ***,. K 1 2 2,.,,,.,.,.,,.,. :,,, : 2009/08/19 : 2009/09/09 : 2009/09/30 * 2007 ** *** ( : 27 2, 17-31, 2009. -, * ** ***,. K 1 2 2,.,,,.,.,.,,.,. :,,, : 2009/08/19 : 2009/09/09 : 2009/09/30 * 2007 ** *** (: dminkim@cau.ac.kr) 18 한국교육문제연구제 27 권 2 호, 2009. Ⅰ. (,,, 2004). (,, 2006).,,, (Myrick,

More information

16_이주용_155~163.hwp

16_이주용_155~163.hwp 사상체질의학회지 2008;20(2):155-163 J of Sasang Constitutional Medicine Vol. 20, No. 2, 2008:155-163 http://www.esasang.com 腦 梗 塞 으로 발생한 少 陽 人 半 身 舞 蹈 病 患 者 치험 1례 이주용 이한얼 한경수 안택원 Abstract 대전대학교 한의과대학 사상체질과 A Soyangin

More information

(....).hwp

(....).hwp sugar cane 계분 (%) a ATCC : American type Culture Collection, b IFO : Institute for fermentation, osaka, c MPNU : Mycological lab. Pusan National University d Mycelial

More information

한국전지학회 춘계학술대회 Contents 기조강연 LI GU 06 초강연 김동욱 09 안재평 10 정창훈 11 이규태 12 문준영 13 한병찬 14 최원창 15 박철호 16 안동준 17 최남순 18 김일태 19 포스터 강준섭 23 윤영준 24 도수정 25 강준희 26

한국전지학회 춘계학술대회 Contents 기조강연 LI GU 06 초강연 김동욱 09 안재평 10 정창훈 11 이규태 12 문준영 13 한병찬 14 최원창 15 박철호 16 안동준 17 최남순 18 김일태 19 포스터 강준섭 23 윤영준 24 도수정 25 강준희 26 2015 한국전지학회 춘계학술대회 2일차 한국전지학회 춘계 학술대회(신소재 및 시장동향 관련 주제 발표) 시간 제목 비고 세션 1 차세대 이차전지용 in-situ 분석기술 좌장 : 윤성훈 09:00~09:30 Real-time & Quantitative Analysis of Li-air Battery Materials by In-situ DEMS 김동욱(한국화학연구원)

More information

Journal of Educational Innovation Research 2017, Vol. 27, No. 2, pp DOI: : Researc

Journal of Educational Innovation Research 2017, Vol. 27, No. 2, pp DOI:   : Researc Journal of Educational Innovation Research 2017, Vol. 27, No. 2, pp.251-273 DOI: http://dx.doi.org/10.21024/pnuedi.27.2.201706.251 : 1997 2005 Research Trend Analysis on the Korean Alternative Education

More information

Y 1 Y β α β Independence p qp pq q if X and Y are independent then E(XY)=E(X)*E(Y) so Cov(X,Y) = 0 Covariance can be a measure of departure from independence q Conditional Probability if A and B are

More information

19(1) 02.fm

19(1) 02.fm Korean J. Crystallography Vol. 19, No. 1, pp.7~13, 2008 Ÿ (ICISS) w š t w (2): t w y w œw Surface Structure Analysis of Solids by Impact Collision Ion Scattering Spectroscopy (2): Atomic Structure of Semiconductor

More information

DBPIA-NURIMEDIA

DBPIA-NURIMEDIA e- 비즈니스연구 (The e-business Studies) Volume 17, Number 3, June, 30, 2016:pp. 93~116 ISSN 1229-9936 (Print), ISSN 2466-1716 (Online) 원고접수일심사 ( 수정 ) 게재확정일 2016. 06. 12 2016. 06. 20 2016. 06. 26 ABSTRACT e-

More information

<494352503131335FC1F8B9E6B1B3C0B02E687770>

<494352503131335FC1F8B9E6B1B3C0B02E687770> ICRP 간행물 113 진단 및 중재 절차를 위한 방사선방호 교육훈련 Education and Training in Radiological Protection for Diagnostic and Interventional Procedures 대한방사선방어학회 이 번역본 발간은 2011년도 원자력안전위원회 방사선안전기술 개 발사업 과제 지원(한국동위원소협회로 부터

More information

DBPIA-NURIMEDIA

DBPIA-NURIMEDIA 27(2), 2007, 96-121 S ij k i POP j a i SEXR j i AGER j i BEDDAT j ij i j S ij S ij POP j SEXR j AGER j BEDDAT j k i a i i i L ij = S ij - S ij ---------- S ij S ij = k i POP j a i SEXR j i AGER j i BEDDAT

More information

???? 1

???? 1 The Korean Journal of Applied Statistics (2014) 27(1), 13 20 DOI: http://dx.doi.org/10.5351/kjas.2014.27.1.013 Maximum Tolerated Dose Estimation by Stopping Rule and SM3 Design in a Phase I Clinical Trial

More information

PJTROHMPCJPS.hwp

PJTROHMPCJPS.hwp 제 출 문 농림수산식품부장관 귀하 본 보고서를 트위스트 휠 방식 폐비닐 수거기 개발 과제의 최종보고서로 제출 합니다. 2008년 4월 24일 주관연구기관명: 경 북 대 학 교 총괄연구책임자: 김 태 욱 연 구 원: 조 창 래 연 구 원: 배 석 경 연 구 원: 김 승 현 연 구 원: 신 동 호 연 구 원: 유 기 형 위탁연구기관명: 삼 생 공 업 위탁연구책임자:

More information

Kaes025.hwp

Kaes025.hwp 고위험군유두상갑상선암환자에대한방사성옥소최대허용선량측정법및치료법의검증 Verification of Measurement Methods and Therapeutic Efficacy of Maximum Permissible Dose of I-131 in High Risk Patients with Differentiated Papillary Thyroid Cancer

More information

-, BSF BSF. - BSF BSF ( ),,. BSF -,,,. - BSF, BSF -, rrna, BSF.

-, BSF BSF. - BSF BSF ( ),,. BSF -,,,. - BSF, BSF -, rrna, BSF. 1. 2010 6 1, 2 4 Ⅰ,Ⅱ 2013,, -,. - Human Cell.. -,., Biosand Filter(BSF) - BSF Main Filtering (Biofilm) BSF, BSF ( ),. -, BSF BSF. - BSF BSF ( ),,. BSF -,,,. - BSF,. -. -. -. - 2. BSF -, rrna, BSF. 2. -

More information

Abstract Background : Most hospitalized children will experience physical pain as well as psychological distress. Painful procedure can increase anxie

Abstract Background : Most hospitalized children will experience physical pain as well as psychological distress. Painful procedure can increase anxie Volume 12, Number 1, 92~102, An Intervention Study of Pain Reduction during IV Therapy in Hospitalized Children Myo-Jin Kim 1), Joung-Hae Bak 1), Won-Seok Seo 2) Mi-Young Kim 3), Sun-Kyoung Park 3), Jai-Soung

More information

<31372DB9DABAB4C8A32E687770>

<31372DB9DABAB4C8A32E687770> 김경환 박병호 충북대학교 도시공학과 (2010. 5. 27. 접수 / 2011. 11. 23. 채택) Developing the Traffic Severity by Type Kyung-Hwan Kim Byung Ho Park Department of Urban Engineering, Chungbuk National University (Received May

More information

( )Kjhps043.hwp

( )Kjhps043.hwp Difference of Fistula Maturation Degree and Physical Property by the Types of Tube Material: An Experimental Study Sang Koo Kang, M.D. 1, Hee Chul Yu, M.D. 1,4, Woo Sung Moon, M.D. 2,4, Ju Hyoung Lee,

More information

V V V α Azam, M. Z. M. & Park, Dong-Ho (2012). The relationship between Digit Ratio(2D:4D) and Physical Fitness in Children. Journal of Korean Society of Living Environmental System, 19(1), 101-110.

More information

( )Kju225.hwp

( )Kju225.hwp 비임균성비뇨생식기감염에서 의진단적효용성 Usefulness of the Mycofast Test (MYCOFAST Evolution 2) for the Diagnosis of Nongonococcal Genitourinary Infections Hang Ro Park, Yang Hyun Kim, Ho Jae Lee, Jea Sang Oh, Hyoung Jin

More information

Journal of Educational Innovation Research 2017, Vol. 27, No. 3, pp DOI: (NCS) Method of Con

Journal of Educational Innovation Research 2017, Vol. 27, No. 3, pp DOI:   (NCS) Method of Con Journal of Educational Innovation Research 2017, Vol. 27, No. 3, pp.181-212 DOI: http://dx.doi.org/10.21024/pnuedi.27.3.201709.181 (NCS) Method of Constructing and Using the Differentiated National Competency

More information

l l l l l l l l l Lee, Geon Kook None This project was designed to establish the Tumor Bank of National Cancer Center in 2000. From the first tumor sample in 2000, the total of tumor and tumor-related

More information

THE JOURNAL OF KOREAN INSTITUTE OF ELECTROMAGNETIC ENGINEERING AND SCIENCE. vol. 29, no. 10, Oct ,,. 0.5 %.., cm mm FR4 (ε r =4.4)

THE JOURNAL OF KOREAN INSTITUTE OF ELECTROMAGNETIC ENGINEERING AND SCIENCE. vol. 29, no. 10, Oct ,,. 0.5 %.., cm mm FR4 (ε r =4.4) THE JOURNAL OF KOREAN INSTITUTE OF ELECTROMAGNETIC ENGINEERING AND SCIENCE. 2018 Oct.; 29(10), 799 804. http://dx.doi.org/10.5515/kjkiees.2018.29.10.799 ISSN 1226-3133 (Print) ISSN 2288-226X (Online) Method

More information

박선영무선충전-내지

박선영무선충전-내지 2013 Wireless Charge and NFC Technology Trend and Market Analysis 05 13 19 29 35 45 55 63 67 06 07 08 09 10 11 14 15 16 17 20 21 22 23 24 25 26 27 28 29 30 31 32 33 36 37 38 39 40

More information

<BFACBCBCC0C7BBE7C7D02831302031203139292E687770>

<BFACBCBCC0C7BBE7C7D02831302031203139292E687770> 延 世 醫 史 學 제12권 제2호: 29-40, 2009년 12월 Yonsei J Med Hist 12(2): 29-40, 2009 특집논문 3 한국사회의 낙태에 대한 인식변화 이 현 숙 이화여대 한국문화연구원 1. 들어가며 1998년 내가 나이 마흔에 예기치 않은 임신을 하게 되었을 때, 내 주변 사람들은 모두 들 너무나도 쉽게 나에게 임신중절을 권하였다.

More information

부문별 에너지원 수요의 변동특성 및 공통변동에 미치는 거시적 요인들의 영향력 분석

부문별 에너지원 수요의 변동특성 및 공통변동에 미치는 거시적 요인들의 영향력 분석 에너지경제연구 Korean Energy Economic Review Volume 15, Number 1, March 2016 : pp. 33 ~ 67 부문별에너지원수요의변동특성및공통변동에 미치는거시적요인들의영향력분석 33 ~ < 표 1> 에너지소비량과주요변수들의연평균증가율 ~ ~ ~ ~ ~ 34 35 36 37 38 ~ 39 [ 그림 1] 부문별에너지원소비량의증가율

More information

Jkafm093.hwp

Jkafm093.hwp 가정의학회지 2004;25:721-739 비만은 심혈관 질환, 고혈압 및 당뇨병에 각각 위험요인이고 다양한 내과적, 심리적 장애와 연관이 있는 질병이다. 체중감소는 비만한 사람들에 있어 이런 위험을 감소시키고 이들 병발 질환을 호전시킨다고 알려져 있고 일반적으로 많은 사람들에게 건강을 호전시킬 것이라는 믿음이 있어 왔다. 그러나 이런 믿음을 지지하는 연구들은

More information

Æ÷Àå½Ã¼³94š

Æ÷Àå½Ã¼³94š Cho, Mun Jin (E-mail: mjcho@ex.co.kr) ABSTRACT PURPOSES : The performance of tack coat, commonly used for layer interface bonding, is affected by application rate and curing time. In this study, bonding

More information

(Exposure) Exposure (Exposure Assesment) EMF Unknown to mechanism Health Effect (Effect) Unknown to mechanism Behavior pattern (Micro- Environment) Re

(Exposure) Exposure (Exposure Assesment) EMF Unknown to mechanism Health Effect (Effect) Unknown to mechanism Behavior pattern (Micro- Environment) Re EMF Health Effect 2003 10 20 21-29 2-10 - - ( ) area spot measurement - - 1 (Exposure) Exposure (Exposure Assesment) EMF Unknown to mechanism Health Effect (Effect) Unknown to mechanism Behavior pattern

More information

550호(01-09)

550호(01-09) T H E K O R E A N D O C T O R S W E E K L Y www.docdocdoc.co.kr I N S I D E 38 3 5 6 8 11 13 24 25 27 29 31 38 41 42 2 Advertisement Government & Medicine 3 Government & Medicine 4 Government & Medicine

More information

DBPIA-NURIMEDIA

DBPIA-NURIMEDIA The e-business Studies Volume 17, Number 6, December, 30, 2016:275~289 Received: 2016/12/02, Accepted: 2016/12/22 Revised: 2016/12/20, Published: 2016/12/30 [ABSTRACT] SNS is used in various fields. Although

More information

ÀÇÇа�ÁÂc00Ì»óÀÏ˘

ÀÇÇа�ÁÂc00Ì»óÀÏ˘ Common Allergic Diseases in Children Sang - Il Lee, M.D. Department of pediatrics Sungkyunkwan University School of Medicine, Samsung Medical Center E - mail : silee@smc.samsung.co.kr Abstract Allergy

More information

Abstract Musculoskeletal Symptoms and Related Factors for Nurses and Radiological Technologists Wearing a Lead Apron for Radiation Pro t e c t i o n Jung-Im Yoo, Jung-Wan Koo 1 ) Angio Unit, Team of Radiology,

More information

- iii - - i - - ii - - iii - 국문요약 종합병원남자간호사가지각하는조직공정성 사회정체성과 조직시민행동과의관계 - iv - - v - - 1 - - 2 - - 3 - - 4 - - 5 - - 6 - - 7 - - 8 - - 9 - - 10 - - 11 - - 12 - - 13 - - 14 - α α α α - 15 - α α α α α α

More information

歯1.PDF

歯1.PDF 200176 .,.,.,. 5... 1/2. /. / 2. . 293.33 (54.32%), 65.54(12.13%), / 53.80(9.96%), 25.60(4.74%), 5.22(0.97%). / 3 S (1997)14.59% (1971) 10%, (1977).5%~11.5%, (1986)

More information

대한한의학원전학회지24권6호-전체최종.hwp

대한한의학원전학회지24권6호-전체최종.hwp 小兒藥證直訣 의 五臟辨證에 대한 小考 - 病證과 處方을 중심으로 1 2 慶熙大學校大學校 韓醫學科大學 原典學敎室 ㆍ 韓醫學古典硏究所 白裕相1,2*1)2) A study on The Diagnosis and Treatment Using The Theory of Five Organs in Soayakjeungjikgyeol(小兒藥證直訣) 1 Dept. of Oriental

More information

<303720C7CFC1A4BCF86F6B2E687770>

<303720C7CFC1A4BCF86F6B2E687770> 1) < 論 文 > 라이프스타일 세분화를 통한 실버타운 수요자 분석 133 주택연구 제15권 4호 2007. 12/15(4) : 133~160 Housing Studies Review Vol. 15, No. 4 : 133~160 접수일 : 2007. 7. 9, 심사일 : 2007. 7. 16, 심사완료일 : 2007. 8. 29 라이프스타일 세분화를 통한 실버타운

More information

09권오설_ok.hwp

09권오설_ok.hwp (JBE Vol. 19, No. 5, September 2014) (Regular Paper) 19 5, 2014 9 (JBE Vol. 19, No. 5, September 2014) http://dx.doi.org/10.5909/jbe.2014.19.5.656 ISSN 2287-9137 (Online) ISSN 1226-7953 (Print) a) Reduction

More information

139~144 ¿À°ø¾àħ

139~144 ¿À°ø¾àħ 2 139 DOI : 10.3831/KPI.2010.13.2.139 2 Received : 10. 04. 08 Revised : 10. 04. 26 Two Case Report on Wrist Ganglion Treated with Scolopendrid Pharmacopuncture Accepted : 10. 05. 04 Key Words: Wrist Ganglion,

More information

<B9AEC8ADB0E6C1A6BFACB1B820C1A63137B1C720C1A633C8A3283135303131332033C2F720BCF6C1A4BABB292E687770>

<B9AEC8ADB0E6C1A6BFACB1B820C1A63137B1C720C1A633C8A3283135303131332033C2F720BCF6C1A4BABB292E687770> 한국문화경제학회 문화경제연구 제17권 제3호, 2014년 12월, pp.189~223 드라마 제작 영유 기업들의 변화와 성장: 상장기업을 중심으로 7년간의 사업현황 검토 김 훈 * 김 정 훈 ** 목 차 Ⅰ. 서 론 Ⅱ. 국내 엔터테인먼트 시장규모 및 제작시장 현황 Ⅲ. 상장기업 경영 현황 조사결과 Ⅳ. 결론 및 시사점 한국 드라마산업은 한류를 이끄는 주요산업으로

More information

untitled

untitled ª Œª Œ 27ƒ 2B Á 2007 3œ pp. 193 ~ 199 ª ƒ w d w ƒ sƒ Methodology of Drought Assessment Using National Groundwater Monitoring Network Data «x Á½ Kwon, Hyung JoongÁKim, Seong Joon Abstract The objective

More information