폐결핵으로 오인된 SIADH를 동반한 편평상피 세포폐암 1예

김순제,류하근,김선두,이길도,박봉안,류주성,유재등,김인숙,신현준,문언수 대한노인병학회 1999 Annals of geriatric medicine and research Vol.3 No.4

Mycophenolic Acid가 PDGF에 의해 증식 유도된 흰쥐 혈관평활근 세포에서 NAD(P)H Oxidase, 세포내 활성산소족 및 Mitogen-activated Protein Kinases에 미치는 영향

박제현,하헌주,김명수,허규하,김유선 이화여자대학교 약학연구소 2004 藥學硏究論文集 Vol.- No.14

Background: Vascular smooth muscle cell (VSMC) proliferation plays an important role in the development and progression of chronic allograft vasculopathy as in atherosclerosis. We already reported that mycophenolic acid (MPA) inhibited VSMC proliferation, cellular reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPK) in human VSMCs. In this study, we examined further molecular mechanisms involved in the anti-proliferative effect of MPA in rat VSMCs. Methods: Primary rat VSMCs were stimulated with PDGF-BB 10 ng/mL in the presence or absence of MPA and various kinds of cell signaling inhibitors. Cell proliferation was assessed by [H³]-thymidine incorporation, NAD(P)H oxidase subunits mRNA expression by RT-PCR, dichlorofluorescein-sensitive cellular ROS by FACS, and the activation of PDGF receptor-β (Tyr 751), racl, and MAPK by Western blot analysis. Results: PDGF increased cell proliferation and cellular ROS, activation of PDGF receptor-β (Tyr 751), racl, expression of p22phox and MOX1 mRNA, ERK 1/2, and p38 MAPK, compared to control. MPA inhibited up-regulation of racl phosphorylation, p22phox and MOX1 mRNA expression, cellular ROS, and phosphorylation of ERK 1/2 and p38 MAPK. However, MPA did not affect PDGF receptor-β (Tyr 751) activation. Wortmannin, diphenyleniodonium (DPI), trolox, and NAC, each inhibited PDGF-induced ERK 1/2 and p38 MAPK activation. PD98059 and p38 MAPK inhibitor also inhibited PDGF-induced cell proliferation. Conclusion: These results suggest that MPA inhibits PDGF-induced VSMC proliferation through inhibiting NAD(P)H oxidase-dependent cellular ROS leading to ERK 1/2 and p38 MAPK activation. 배경 : 혈관평활근 세포의 증식은 장기이식 후 발생하는 혈관경화증이나 동맥경화증의 발생과 진행에 중요한 역할을 한다. Mycophenolic acid (MPA)는 강력한 면역억제제로서 혈관평활근 세포의 증식도 억제한다. 본 연구는 사람의 혈관평활근 세포에서 MPK가 세포증식에 관여하는 신호전달계인 활성산소족과 mitogen-activated protein kinases(MAPK) 활성화를 억제하는 기존의 연구결과를 바탕으로, PDGF에 의해 증식 유도된 흰쥐 혈관평활근 세포에서 MPA가 세포의 증식을 억제하는 기전을 검색하였다. 방법 : 일차 배양한 흰쥐 혈관평활근 세포를 PDGF-BB 10 ng/mL로 자극하였고, MPA를 비롯한 여러 종류의 신호전달 억제제는 PDGF를 투여하기 1시간 전에 투여하였다. 세포증식은 [H³]-thymidine incorporation으로, NAD(P)H oxidase subunit의 mRNA 표현은 RT-PCR로, dichlorofluorescein에 민감한 세포내 활성산소족은 FACS 방법으로, 그리고 PDGF 수용체-β (Tyr 751), racl 및 MARK 활성하는 Western blot으로 각각 분석하였다. 결과 : PDGF는 PDGF 수용체-β (Tyr 751)의 활성화 및 NAD(P)H oxidase subunit 중 racl의 활성화와 p22phox와 MOX1의 mRNA 표현을 대조군에 비하여 유의하게 증가시켰다. MPA는 PDGF 수용체의 활성화에는 영향을 주지 않았으나, racl의 활성화, p22phox와 MOX1의 mRNA 표현의 상향 조절, 세포내 활성산소족, 그리고 ERK 1/2와 p38 MAPK의 활의한 EFK 1/2와 p38 MAPK 활성화와 세포 증식을 억제하였다. PD98059와 p38 MAPK 억제제는 PDGF에 의한 혈관평활근 세포의 증식을 억제하였다. 결론 : 본 연구결과는 MPA가 NAD(P)H oxidase를 억제함으로써 세포내 활성산소족 생산과, MAPK 활성화를 억제함으로써 PDGF에 의하여 유도되는 혈관평활근 세포의 증식을 억제함을 시사하였다.

남성화 암쥐의 모리스 수중 미로 수행력 : 성에 따른 공간기억력과 테스토르테론 효과의 차이

신성현,박제민,정우영,박문일,서유나,김성곤,강철중 大韓神經精神醫學會 2007 신경정신의학 Vol.46 No.5

Objectives : It is widely accepted that gonadal steroids are involved in organization and activation of sexual dimorphism in the brain areas related with spatial leaming. This study aimed to test the following hypothesis : 1) spatial memory is affected by sex, 2) this difference is related with brain differentiation by exposure to testosterone in the neonatal period, and/or 3) the sexual difference of spatial memory is the result of the interaction between organization of sexual dimorphism in the brain and the circulating testosterone after growing up. Methods : Testosterone enanthate 100 ㎍, ('androgenized') orvehicle ('control') was randomly administered to 28 female and 25 male rat pups within 24 hour of birth. The escape latencies (EL) in Morris water maze were measured in 15 and 16 week of age with vehicle ('baseline') and with 10 μmol/kg of testosterone ('with testosterone'), respectively. Each session Consis-ted of 10 trials, and means of the last 5 trials were analyzed. Results : The baseline EL of the males were significantly shorter than females regardless ofneonatal exposure to testosterone. With testosterone, EL of the androgenized females were significantly shorter than control females and comparable to those of males. Conclusion : Neonatal exposure to testosterone in female rats may develop a tesosterone-dependent male-like spatial leaming system.

Mycophenolic Acid와 Rapamycin이 흰쥐 사구체 혈관간세포증식과 세포외기질 생성에 미치는 영향

김명수,박제현,하헌주,허규하,서지연,김유선,김혜진,박기일 이화여자대학교 약학연구소 2004 藥學硏究論文集 Vol.- No.14

Background: Excess proliferation and extracellular matrix (ECM) accumulation of mesenchymal cells such as vascular smooth muscle cells (VSMC) and glomerular mesangial cells cause chronic allograft nephropathy showing transplant vascular sclerosis and glomerulosclerosis. Mycophenolic acid (MPA) and rapamycin (RPM) are well known as strong inhibitors of VSMC proliferation, but their effects on the glomerular mesangial cells are not yet clearly understood. This study examined the effects of MPA or RPM on PDGF-induced proliferation and ECM accumulation in rat glomerular mesangial cells. Methods: Mesangial cells isolated from the glomeruli of Sprague-Dawley rats were cultured with DMEM containing 20% fetal bovine serum. Growth arrested and synchronized cells were administered with test drugs (MPA10 nM-10μM, RPM 0.1 nM-1μM) before the addition of PDGF 10 ng/mL. Cell proliferation was assessed by [³H]thymidine incorporation, collagen by [³H]proline incorporation, and fibronectin, ERK, and p38 MAPK by Western blot analysis. Results: PDGF increased mesangial cell proliferation by 4.64-fold. Compared to stimulated control, MPA above 500 nM and RPM above 10nM showed a significant inhibitory effect in a dose-dependent manner. The IC_(50) of MPA and RPM against PDGF-induced mesangial cell proliferation were around 500 nM and 100 nM, respectively. The collagen synthesis was also inhibited by MPA and RPM, but the fibronectin secretion was inhibited by MPA alone. The proliferation of mesangial cell correlated with activation of ERK and. p38 MAPK. MPA, but not RPM, inhibited ERK and p38 MAPK activation. Conclusion: This study demonstrated that MPA and RPM significantly inhibited PDGF-induced proliferation and ECM production in rat glomerular mesangial cells. The inhibitory effects of MPA, but not RPM, are correlated with ERK and p38 MAPK.

녹동균 세포외막 단백질 백신 CFC-1-101의 안정성 및 면역원성 검토 : 임상 제 Ⅰ/Ⅱa상 시험

장인진,김익상,유경상,임동석,김형기,신상구,장우현,박완제,이나경,정상보,안동호,조양제,안보영,이윤하,김영지,남성우,김현수 대한감염학회 1998 감염 Vol.30 No.3

목적 : 제일제당에서는 녹농균의 세포외막 단밸질을 유효성분으로 하는 백신인 CFC-101을 개발하였으며, 동물시험에서 이 백신의 안전성과 유효성을 입증하였다. 본 연구에서는 이 녹농균 백신의 인체에 대한 안전성과 면역원성을 평가하는 동시에 인체 접종시의 최적 투여 용량을 결정하기 위하여 제 I/Ⅱa상 임상시험을 수행하였다. 방법 : 건강한 성인 남자를 피험자로 선별하여 각 용량군에 백신투여자 6명, 위약투여자 2명을 배정하였다. 백신 투여군은 0.25mg, 0.5mg 또는 1.0mg 용량의 녹농균 백신을 7일 간격으로 3회에 걸쳐 근육주사 하였으며, 위약 투여군에게는 세포외막 단백질을 제외한 동일한 성분을 투여하였다. 백신접종 후 국소적 또는 전신적인 반응의 발생여부를 관찰하고, 혈액시료를 체취하여 백신의 역가와 유효성을 검정하였다. 결과 : 녹농균 백신 CFC-101은 모든 접종자에서 양호한 내약성을 보였다. 또한 0.5mg 과 1.0mg 백신 투여군에서는 100%의 항체양전율을 나타내었다. 생성된 항체는 녹농균 세포외막단백질에 특이성을 보였고, 녹농균 감염에 대해 방어효능이 있었다. 결론 : 이와같은 결과로부터 이 녹농균 백신은 인체에 안전하게 투여할 수 있으며, 높은 항체 생성능으로 감염방어 효능을 보이고 0.5mg과 1.0mg이 최적용량인 것으로 판단되었다. Background : We developed a Pseudomonas aeruginosa outer membrane protein(OMP) vaccine CFC-101, and the prophylactic efficacy of which has been demonstrated in animal models. In order to evaluate the safety and immunogenicity of the P. aeruginosa vaccine, we carried out a phase I/Ⅱa clinical trial in healthy male volunteers. Methods : Groups of eight volunteers, including two placebo subjects, were vaccinated intramuscularly with three doses of 0.25, 0.5 or 1.0 mg of the vaccine at one week intervals. Sings of systemic and local reactions observed after vaccination were recorded for each vaccinee for 5 days. Physical examinations were performed on days 0, 1, 7, 8, 14, 15, 21, and 42, and clinical laboratory tests were done on days 0, 3, and 21. Blood samples for assay of serum antibody levels were obtained up to 42 days after the first vaccination. Results : The vaccine was generally well tolerated by all vaccinees, showing no significant side effects. In the three dosage groups, all vaccinees, except one receiving the 0.25 mg dose, showed significant elevation in serum IgG antibody titers against the vaccine proteins, indicating 100% seroconversion in 0.5 and 1.0 mg groups. The human antibodies induced by the vaccine were specific for P. aeruginosa OMPs, as confirmed by western blot analysis and immunoprecipitation assays. The capacity of the human antisera to enhance opsonophagocytic killing activity by polymorphonuclear leukocytes and to confer protection against P. aeruginosa infections indicates that the antibodies elicited by the vaccine have protective efficacy. Conclusion : We conclude that the P. aeruginosa OMP vaccine is safe and effective for human use and its optimal dose to be 0.5 or 1.0 mg.

3-MCPD의 생식˙발생독성에 관한 연구

곽승준(Seung Jun Kwack),김순선(Soon Sun Kim),최요우(Yo Woo Choi),이규식(Gyu Seek Rhee),손경희(Kyung Hee Sohn),이이다(Rhee Da Lee),채수영(Soo Young Chae),정용현(Yong-Hyun Chung1),유일재(Il Je Yu1),박귀례(Kui Lea Park) 한국독성학회 2004 Toxicological Research Vol.20 No.2

3-Monochloro-1,2-propanediol(3-MCPD) is a toxic compound, often present in different foods containing acid hydrolyzed(AH) protein, like seasonings and savory food products. The purpose of the present study was to investigate the effects of 3-MCPD on male fertility, sperm and testosterone secretion. In vivo male fertility test was performed for observing the adverse effects of 3-MCPD on the function of male reproductive system and pregnancy outcome. 0.01, 0.05, 0.25, 1 and 5 mg/kg b.w. of 3-MCPD was given daily by gavage to groups of 15 adult male SD rats for 4 weeks. At the end of pre-treatment period, males were mated overnight with normal females. Following morning, males demonstrating successful induction of pregnancy were sacrificed on that day to assess sperm parameters and histopathology of reproductive organs. The resulting pregnant females were sacrificed on day 20 of gestation to evaluate pregnancy outcome. As a result, four-week paternal administration with 3-MCPD resulted in adverse effects on male fertility and pregnancy outcome without remarkable histopathological changes in testes and epididymides; sperm motility, copulation index and fertility index were markedly decreased in the treated group and numbers of live fetuses showed steep dose-response curves. Also, spermatogenesis was investigated in this experiment. However, no<br/> effect was observed on production of sperm in testes treated with 3-MCPD for 4 weeks. Hormone assay was performed for observing the effects of 3-MCPD on testosterone and luteinizing hormone (LH) in blood and testes of male SD rats and cultured primary Leydig cell. In result, significant changes of related hormones did not observed by treatment of 3-MCPD. These results indicated that paternal treatment with 3-MCPD induced spermatotoxic effect, which caused an antifertility on male.

ORC용 스크롤 팽창기 설계

유제승(Je Seung Yu),김현재(Hyun Jae Kim),김우영(Woo Young Kim),김현진(Hyun Jin Kim) 대한설비공학회 2010 대한설비공학회 학술발표대회논문집 Vol.2010 No.11

Low-grade heat is frequently encountered as a by-product in industrial processes. However, waste heat recovery is generally considered to be a technologically challenge and is rarely economically viable. One possible way of increasing the use of low-grade heat is to utilize Rankine cycle in order to convert low-grade heat to high-grade quality energy such as electricity. This paper addresses a shaft power generation by using a scroll expander in an organic Rankine cycle with R134a as a working fluid, where heat is supplied from an engine coolant. Design practice of a scroll expander has been carried out for 1.5 ㎾ power output, and the expander performance has been analyzed by numerical simulation.

엔진 냉각수 폐열 회수용 스크롤 팽창기 설계

유제승(Je Seung Yu),김현재(Hyun Jae Kim),김현진(Hyun Jin Kim) 대한설비공학회 2011 설비공학 논문집 Vol.23 No.12

A scroll expander was designed for an energy converter from waste heat of IC engine coolant to useful shaft work. The scroll expander is to run in a Rankine cycle which receives heat energy transferred from engine coolant circulation cycle. The working fluid was Ethanol. For axial compliance, a back pressure chamber was provided on the rear side of the orbiting scroll. Lubrication oil was delivered by a positive displacement type oil pump driven by the shaft rotation. Performance analysis on the scroll expander showed that the expander efficiency was 63.4%. It extracts shaft power of 0.6 kW out of engine coolant waste heat of 17.5 kW, resulting in the Rankine cycle efficiency of 3.43%.

AUF1 promotes let-7b loading on Argonaute 2

Yoon, Je-Hyun,Jo, Myung Hyun,White, Elizabeth J.F.,De, Supriyo,Hafner, Markus,Zucconi, Beth E.,Abdelmohsen, Kotb,Martindale, Jennifer L.,Yang, Xiaoling,Wood III, William H.,Shin, Yu Mi,Song, Ji-Joon,T Cold Spring Harbor Laboratory Press 2015 Genes & development Vol.29 No.15

<P>Yoon et al. discovered that RBP AU-rich-binding factor 1 (AUF1) promotes let-7b loading onto Argonaute 2 (AGO2), the catalytic component of the RNA-induced silencing complex (RISC). In turn, AGO2–let-7 triggered target mRNA decay.</P><P>Eukaryotic gene expression is tightly regulated post-transcriptionally by RNA-binding proteins (RBPs) and microRNAs. The RBP AU-rich-binding factor 1 (AUF1) isoform p37 was found to have high affinity for the microRNA let-7b in vitro (<I>K</I><SUB>d</SUB> = ∼6 nM) in cells. Ribonucleoprotein immunoprecipitation, in vitro association, and single-molecule-binding analyses revealed that AUF1 promoted let-7b loading onto Argonaute 2 (AGO2), the catalytic component of the RNA-induced silencing complex (RISC). In turn, AGO2–let-7 triggered target mRNA decay. Our findings uncover a novel mechanism by which AUF1 binding and transfer of microRNA let-7 to AGO2 facilitates let-7-elicited gene silencing.</P>

폴리아마이드 역삼투막의 염소내성에 대한 연구

유지현 ( Ji Hyun Yu ),백영빈 ( Young Bin Baek ),안창훈 ( Chang Hoon Ahn ),김승현 ( Seung Hyun Kim ),윤제용 ( Je Yong Yoon ) 한국물환경학회(구 한국수질보전학회) 2011 한국물환경학회·대한상하수도학회 공동 춘계학술발표회 Vol.2011 No.-