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.

로자탄 대 포시노프릴의 고혈압 환자들에서 항고혈압 효과, 안전성 및 내약성의 비교

박대균,이명묵,채인호,이무용,이홍자,김효수,김철호,손대원,오병희,박영배,최윤식 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.1

비복근건 부분절단술을 통한 종아리성형술

박원진,이태희,신명수 大韓成形外科學會 1999 Archives of Plastic Surgery Vol.26 No.3

A muscular calf is esthetically unappealing in Asian women. Treatment by liposuction alone has poroven to be difficult due to a small amount of fat. We established a new method of transecting half of the gastrocnemius tendon in order to improve the contour of the calf. Thirty-five patients were operated on during the past 3 years. The medial or lateral half of the gastrocnemius tendon was cut using an endoscopic-guided 3M AGEE blade through a 1cm-sized incision. The portion of the muscle above the site of the transection was elevated from the underlying soleus muscles. We checked the calf circumference and evaluated the clinical results at 6 months postoperatively. An average 10% reduction in calf circumfernce was measured, showing a significant esthetic improvement. There were no significant changes in gait analysis or in the Cybex test. There were no specific complications related to the procedure. Through our clinical experience in 35 cases, we were able to prove that tenotomy is a effective, simple and easy method without severe morbidity.

급성 백혈병 환자에서 발생한 감염 양상의 분석(1986~1992)

박선양,오명돈,김양수,백경란,김병국,최강원,김성민 대한감염학회 1993 감염 Vol.25 No.3

Infection is a major complication and potentially life-threatening in patients with acute leukemia. The patients require prompt broad-spectrum antibiotics therapy when fever develops. One of the keys to successful patient management is the recognition of institutional trends of the spectrum of infections and infecting microorganisms. So we evaluated 138 patients with acute leukemia and blastic crisis of chronic myelogenous leukemia admitted to Seoul National University Hospital from July 1986 to June 1992. The results are following: 1) Total number of febrile episodes was 224 and 60% of them occurred after chemotherapy. 2) Microbiologically-defined infection, clinically-defined infection, and unexplained fever accounted for 28%, 45%, 27% of the febrile episodes respectively. 3) Fifty-eight percent of microbiologically-defined infections were caused by gram-negative bactria, and 36% were gram-positive bacteria. There was a tendency to a greater proportion of gram (+) organisms than that of the last study (p>0.1). Escherichia coli was the most common organism, and coagulase-negative staphylococci, Pseudomonas aeruginosa, Klebsiella pneumoniae were common in decreasing order. 4) Pneumonia was the most common type of infection, followed by skin and soft tissue infection, perianal infection, gingivitis and primary septicemia. 5) Seventy-two percent of total infections improved with therapy and this success rate was higher than that of the last study(p<0.001).

임산부에서 발생한 폐크립토콕쿠스증을 동반한 크립토콕쿠스 수막뇌염 1예

박경화,송진수,최평균,방지환,조재현,박완범,김홍빈,김남중,오명돈,최강원 대한감염학회 2006 감염과 화학요법 Vol.38 No.4

Cryptoccus necoformans는 면역기능이 저하된 환자에서 기회 감염을 일으키는 진균이나 정상인에서도 드물게 질병을 일으킨다. 그러나 임산부에서 폐크립토콕쿠스증을 동반한 크립토콕쿠스 수막염의 보고는 아주 드물다. 저자들은 분만 후에도 악화되는 두통과 의식저하로 내원한 임신 37주의 임산부에서 뇌척수액과 폐조직검사를 통해 폐크립토콕쿠스증을 동반한 크립토콕쿠스 수막뇌염을 진단하고 항진균제를 사용하여 치료하였다. 본 증례처럼 명백한 기저질환이 없는 임산부에서도 크립토콕쿠스 수막염은 발생할 수 있으므로 의심이 되면 뇌척수액검사를 포함한 진단적 검사를 시행하고 적절한 치료를 시작해야한다. 그리고 임산부에서 크립토콕쿠스증이 발생한 경우의 치료에 대하여 문헌 고찰과 함께 보고하는 바이다. Cryptoccocosis occurs more frequently in immunocompromised hosts such as patients with AIDS, lymphoma, leukemia and other debilitating diseases. Pulmonary cryptococcosis can occur in the absence of any recognized immunodeficiency and cryptococcal meningitis can occur rarely during pregnancy. Although it is extremely rare, we encounter the reports of case of cryptococcal pneumonia and combined cryptococcal meningitis during pregnancy. We present here that 36-year-old pregnant woman, who was previously healthy, with cryptococcal meningoencephalitis and cryptococcal pneumonia was treated with amphotericin B and flucytosine. The maternal outcome was favorable, and there is no evidence of congenital infection in the newborn.

변형된 측경부 전진피판술을 이용한 익상경 기형의 교정

신명수,박철규 大韓成形外科學會 1991 Archives of Plastic Surgery Vol.18 No.1

Pterygium colli is a congenital malformation characterized by bilateral webbing of the neck extending from the mastoid to the acromion. The etiology of the webbed neck deformity is variable which include chromosomal abnormality, congenital disease and jugular lymphatic obstruction sequence. Aims of the surgical correction is to create a normal neck contour with a symmetrical posterior hairline while avoiding obvious scarring especially on the anterior and lateral neck. We used modified lateral cervical advancement technique for the correction of 3 cases of webbed neck deformity. All scars lie within or along the hairline and extend onto the posterolateral shoulder area. And this modification also provided natural hairine and neck controur. We can avoid tension suture and vertical suture line for the prevention of scar spreading by this medthod. There was no recurrence of neck deformity during 6 month to 2 year follow up period.

강성사면에 인접한 옹벽의 거동에 관한 연구

이명욱,유남재,박병수 江原大學校 産業技術硏究所 1998 産業技術硏究 Vol.18 No.-

This thesis is an experimental and numerical research on beating capacity acting retaining walls close to rigid slopes with stiff angles. Experiments were performed with changing the roughness of adjacent slope to the wall, its inclination, distance between wall and slope. Vertical stress and applied surcharge loads were measured by miniature earth cells and a load cel respectively. Stress distribution Vertical Settlement of surcharge of rigid model footing were measured by LVDTs. Bearing capacities of surcharge loads were compared with theoretical estimations by using several different methods of limit equilibrium and numerical analysis. For limit equilibrium methods, the modified silo and the wedge theories, proposed by Chung sung gyo and Chung in gyo(1994) were used to analyze test results Based on those modified theories, the particular solution with the boundary condition of surcharge loads on the surface of backfill was obtained to find the stress distributions acting in the backfill and to compare with test results. From results of surcharge test with model wall being very close to the slope, analyzed results by the modified silo theory and to be in the better agrements than other methods.

사회심리적요인에 따른 스포츠소비행동 연구

정명수,박준희,김유수 조선대학교 통계연구소 1999 統計硏究所論文誌 Vol.1 No.1

The purpose of this study was to identify the social and psychological variables associated with sport consumption. A questionnaire consisted of 101 items measuring the social and psychological factors related to sport consumption and basic items asking the subject's demographic characteristics and amount of sport consumption through various means was administered to 414 Collegians(159 male and 255 female). The means of spot consumption investigated were viewing sport events in actual sport situations, viewing sports through T.V.. listening to sport broadcasting through radio. and reading newspapers, magazines and books on sports. Factor analyses were conducted on the 101 items and 17 social and psychological factors were found. The social and psychological factors were then used as independent variables for multiple regression analyses in order to identify the variables associated with various means of sport consumption. The main results indicated the following conclusions : (1) The social and psychological variables related to the general sport consumption were learning of sport skills and strategies, entertainment, socialization, curiousty, aesthetics, avoidance of reality, aggression, locality catharsis, stress-seeking, dependance and identification. (2) Variables such as socialization, learning of sport skills and strategies and entertainment were the common variables for all sport consumption besides the common variables. (3) Different social and psychological variables were identified for different means of sport consumption besides the common variables.

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.

달리기 운동 프로그램이 시각장애인의 건강관련 체력에 미치는 영향

이명수,양점홍,홍순미,최재현,박원익,이창준 釜山大學校 附設 體育科學硏究所 2004 體育科學硏究所 論文集 Vol.20 No.-

The purpose of this study was to find out the effect of jogging(LSD ; Long Slow Distance) and walking training on health-related fitness of the blind.....