노화가 인체 중간엽 줄기세포로부터 조골세포로의 증식 및 분화에 미치는 영향

백기현,태현정,오기원,이원영,조정기,권순용,강무일,차봉연,이광우,손호영,강성구,김춘추 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.3

연구배경: 일반적으로 골다공증과 연관된 위험인자로는 연령, 폐경, 약물, 불충분한 칼슘섭취, 만성질환 및 운동부족 등이 있는데, 특히 노화가 진행할수록 골밀도가 감소하는 것은 잘 알려져 있다. 노화와 관련하여 진행되는 골소실은 조골세포 및 전구조골세포의 기능적 결핍에 의한 골형성의 감소가 주요한 요인으로 여겨지고 있다. 그 동안 연령이 조골모 세포의 양과 조골모 세포로부터 성숙조골세포로의 분화 및 증식에 미치는 영향에 대한 일부 보고들이 있었으나 아직 일치된 견해는 없는 형편이다. 방법: 다양한 연령의 사람으로부터 골수를 채취, 중간엽 줄기세포가 포함된 단핵세포를 분리한 후 조골세포로 분화하기 좋은 조건하에서 배양하였다. 대상군은다시 젊은군과 노령군으로 구분하여 다양한 변수를 비교 분석하였다. 일차배양에서는 CFU-F를 계수하여 골수내 중간엽 줄기세포의 수를 추산하였고, 칼슘측정을 통하여 기질의 무기화 정도를 비교하였다. 계대배양후 이차배양에서는 시기별로 알카리성 포스파타제 활성도를 측정하고 오스테오칼신 mRNA의 발현을 관찰하여 젊은군과 노령군 사이의 증식능 차이를 비교하였다. 또한 이차배양 시기별로 MTT 측정을 하여 양군간에 증식능 차이가 있는지 알아보았다. 결과: 1. 일차배양 15일째에 평균 CFU-F의 수는 젊은군에서 유의하게 많았다(젊은군 148.3±28.9, 노령군 54.3±9.1, p=0.02). CFU-F의 평균면적은 젊은군에서 넓은 경향을 보였으나 통계적으로 유의하지는 않았다. 2. 일차배양 17일 경과 후 양군간에 기질 칼슘 침착정도는 유의한 차이를 보이지 않았다(젊은군 103.6±50.6, 노령군: 114.0±56.5, p=NS). 3. 이차배양 10일째에 젊은군에서 알카리성 포스파타제 활성도가 고령군에 비해 유의하게 높았다(젊은군: 935.5±115.0 U/mg, 노령군: 578.4±115.7U/mg,p.0.05). 고령군에서는 시간 경과에 따른 변화가 미약했으며 전반적으로 알카리성 포스파타제의 활성도가 젊은군에 비해 낮았다. 4. 이차배양도중 오스테오칼신 mRNA의 발현은 배양시기별로 젊은군에 비해 고령군에서 더 낮은 경향을 관찰할 수 있었다. 5. 이차배양 10일과 15일에 젊은군에서 노령군보다세포증식이 유의하게 증가된 양상을 보였다(10앓 젊은군 0.73±0.05, 노령군 0.58±0.04, p=0.05, 15일; 젊은군 0.80±0.05, 노령군 0.70±0.03, p=0.05).결론: 이상의 연구에서 저자들은 노령군에서 젊은군보다 골수 내 중간엽줄기세포의 수가 적고, 노령군에서 유래한 전구조골세포의 성숙조골세포로의 증식 및 분화가 젊은군 보다 감소해 있는 것을 관찰할 수 있었다. Background: Osteoblasts originate from osteoprogenitor cells in bone marrow stroma, termed mesenchymal stem cells (MSCs) or bone marrow stromal cells. Each MSC forms colonies (colony forming units-fibroblasts [CFL-Fs]) when cultured ex vivo. There are some reports about the age-related changes of the number and osteogenic potential of osteoprogenitor cells, but any relationship has not been clearly established in humans. In this study, we counted MSCs using CFU-Fs count and examined the proliferative capacity and differentiation potential of osteoprogenitor cells. Finally, we analyzed how these parameters varied with donor age. Methods: Bone marrow was obtained from the iliac crest of young (n=6, 27.2±8.6 years old) and old (n= 10, 57.4k6.7 years old) healthy donors. Mononuclear cells, including MSCs, were isolated and cultured in osteogenic medium. In primary culture, we compared the colony-forming efficiency of MSCs between the two groups and determined the matrix calcification. When primary culture showed near confluence, the cells were subcultured. Alkaline phosphatase activity, osteocalcin expression by RT-PCR and proliferative potential by MTT assay were examined by the time course of secondary culture. Results: At the 15th day of primary culture, the mean number of CFU-Fs was significantly higher in the younger donors (young: 148.3±28.9, old: 54.3±9.1, p=0.02) and the mean size of CFL-Fs was also larger in the younger donors than the older donors. However, matrix calcification was not different between the two groups (young: 103.6±50.6, old: 114.0±56.5, p=NS). In secondary culture, alkaline phosphatase activities were significantly lower in the older donors. The younger donors showed peak alkaline phosphatase activity at day 10, while the older donors didn't showed a remarkable peak (young: 935.5±115.OU/mg, old: 578.4±115.7U/mg, p<0.05). Total cell number as a proliferative index increased progressively during the secondary culture and a significantly greater cell number was noted in the younger donors. Osteocalcin expression was generally upregulated in the younger donors, but this was not statistically significant. Conclusion: Our study shows that the number of osteoprogenitor cells is decreased during aging and that the proliferative capacity and differentiation potential of osteoprogenitor cells seem to be reduced during aging (J Kor SOC Endocrinol 18:296-305, 2003).

좌심방 석회화와 관련된 반복된 좌심방 혈전 1예

김성훈,우성용,오유경,정우백,임철현,신재원,박철수,윤호중,정욱성,홍순조 대한순환기학회 2004 Korean Circulation Journal Vol.34 No.3

간 세포암에서 VEGF, TGF-β1, b-FGF 발현의 의의

김성용,남충현,주종우,채만규,백무준,이문수,김형철,안현철,김홍수,김창진,김창호 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1

Purpose: Angiogenesis is important for the proliferation and the metastasis of solid tumors. The growth of a solid tumor is widely recognized to depend on the process of neovascularrozation. Without angiogenesis, tumors cease to grow beyond even a few milimeters in diameter. It has been shown that tumor vascular density is an independent prognostic marker in several types of human tumors and is known to correlate with poor prognosis. To date, many angiogenic factors have been identified, such as transforming growth factor-α(TGF-α), transforming growth factor-β(TGF-β), fibroblast growth factor family(FGF), vascular endothelial growth factor(VEGF), platelet derived endothelial cell growth factor(PD-ECGF), tumor necrosis factor-α(TNF-α), and angiogenin. Hepatocellular carcinoma(HCC) is the second most common tumor in Korean males and is known as a typical hypervascular tumor with frequent portal vein invastion. The authors identified the expreesion of VEGF, TGF-β1, and b-FGF in HCC specimens and evaluated the relationship between these growth factors and the clinicopathologic characteristics of HCC. Method: We reviewed the medical records of 30 patients who were diagnosed as hepatocellular carinoma treated with hepatic resection between January 1994 and December 1998 in Soonchunhyang University Chunan Hospital. The selection of the cases was decided according to the condition of paraffin block fixation. The prognostic factors such as age, sex, tumor size, concentration of serum α-fetoprotein, presence of liver cirrhosis, presence of tumor emboli in portal vein, TMN stage, amount of transfusion during the operation, hepatitis B virus(HBV) infection, and Edmonson-Steiner(E-S) grade were investigated. Relationship between the prognostic factors and the immunopathologic expression of the TGF-β1, b-FGF, and VEGF was examined. Result: Thirty patients (24 males, 6 females) were included in the current study. The patient's mean age was 50.6 years and the age ranged from 36 to 65 years. The mean size of the tumor was found to be 5.2cm. All the patients were follewed up for 7 to 63 months. Child's classification A patients were 23(76.7%)cases, B patients were 7(23.3%)cases, and C was none. Immunohistochemical staining of HCC tumor mass in VEGF expression patients were 17(56.7%), b-FGF expression patients were 10(33.3%), and TGF-β1 expression patients were 10(33.3%). VEGF expression or more than one positive expression among the three factors correlated with tumor size and the stage of HCC but did not correlated with other clinicopathological characteristics. TGF-β1 and b-FGF did not correlate with any clinicopathological characteristics. Conclusion: The results suggest that the expression of VEGF or more than one positive expression among the three factors in HCC cells may be a significant prognostic factor of HCC.

반코마이신 내성 장구균 감염에 대한 quinupristin-dalfopristin 치료 경험

추은주,최상호,조영환,정선미,김백남,김남중,김미나,김양수,우준희,류지소 대한화학요법학회 2002 대한화학요법학회지 Vol.20 No.1

VRE 감염이 중환자에서 급속히 증가하고 있으나 이에 대한 확실한 치료제가 없어 새로운 항생제에 대한 활발한 연구가 있는데 그 중 하나가 quinupristin/dalfopristin이고, 저자들은 중증 환자들의 VRE 감염에 대해 quinupristin/dalfopristin를 투여하여 치료한 임상적 경험을 하였기에 문헌고찰과 함께 보고하는 바이다. Vancomycin-resistant enterococci (VRE) was first recognized in 1992 in Korea. VRE infection have been increasingly reported in immunosuppressed patients over the past decade and have become one of major nosocomial pathogens. Clinicians carings for patients with VRE infections face severe constraints in the selection of treatment. Quinupristin/dalfopristin is active in vitro againt vancomycin-resistant E. faecium (VREF), with a MIC_(90) of 1.0㎍/mL. We studied the clinical efficacy and safety of this agent in the treatment of VREF infection. Patients were included if they had signs and symptoms of active infection including bacteremia, intra-abdominal infection, and wound infection. A total of 13 patients with VREF infection were enrolled. A favorable clinical response (cure or improvement) occured in 10 of 11 evaluable patients. The only adverse events related to quinupristin/dalfopristin were arthralgia and myalgia, which occurred in 2 of 13 patients. These results suggest that quinupristin/dalfopristin is effective and safe as treatment for VREF infections in critically ill patients with serious underlying conditions.

심전도에서 조기재분극을 보인 특발성 심실세동

이정은,함효주,이관용,노지웅,유진석,정우백 이화여자대학교 의과학연구소 2014 EMJ (Ewha medical journal) Vol.37 No.2

Early repolarization is a common electrocardiographic (ECG) feature found in young adults, men and athletes, and has been considered to be a benign feature for the last several decades. But recent studies suggest that early repolarization may be related to idiopathic ventricular fibrillation and sudden cardiac death. We report a young man, 35 years old, who had life threatening ventricular fibrillation and sudden cardiac arrest. He was evaluated for cardiac causes of ventricular fibrillation. There was no explanation other than that his ECG showed an early repolarization pattern so we treated him with implantable cardioverter defibrillator. Thus, we suggest that early repolarization may be related with life threatening ventricular arrhythmia.

과립구 감소증을 보이는 급성 백혈병 환자에서 tosufloxacin의 감염 예방 효과 : 무작위배정 양안맹검 위약 대조 시험 A randomized, Double-Blind, Placebo-Controlled Trial

김양수,양성연,조용균,김백남,정두련,김은옥,송재훈,우준희,유지소,배직현 대한화학요법학회 1996 대한화학요법학회지 Vol.14 No.1

Background : Infection is a major cause of morbidity and mortality during periods of granulocytopenia in patients with acute leukemia. Several prophylactic antibiotics including quinolones show preventive effect, with some drawbacks including superinfections by gram-positive bactera. Tosufloxacin is a new flucroquinolone that theoretically has the advantage of preventing break-through infection by gram-positive bacteria. Methods :To evaluate the prophylactic efficacy of tosufloxacin in patients with acute leukemia, we performed double-blind, randomized, placebo- controlled trial. Patients were randomized to two group, one of which received tosufloxacin (150mg bid), and the other received placebo. Infection was classified as microbiologically documented infection (MDI), clinically documented infection (CDI), and unexplained fever (UF). Results : From March 1993 to March 1994, Patients with acute leukemia under remission induction or consolidation chemotherapy were enrolled, and 52 patients were finally analysed. The incidence of infection showed no significant difference between tosufloxacin and placebo group(P=0.08), and the incidence of MDI plus CDI(P=0.54) or MDI alone(P=1.0) also showed no difference. MDI by gram-positive organisms was fewer in tosufloxacin than in placebo group. Surveillance culture revealed emergence of tosufloxacin resistant E. coli in 30% of tosufloxacin patients. Conclusion : In conclustion, tosufloxacin failed to show prophylactic efficacy in patients with acute leukemia, and the emergence of resistant gram-negative organisms will be a problem.

8.3% Carbamide Peroxide 함유 펜 형 자가미백제인 BIancTis Forte의 색조개선 및 안전성에 관한 임상연구

이진경,민선홍,홍성태,오소람,정신혜,황영혜,유성엽,배광식,백승호,이우철,손원준,금기연 대한치과보존학회 2009 Restorative Dentistry & Endodontics Vol.34 No.2

This clinical study evaluated the whitening effect and safety of polymer based-pen type BlancTis Forte(NIBEC) containing 8.3% carbamide peroxide. Twenty volunteers used the BlancTis Forte whitening agent for 2 hours twice a day for 4 weeks As a control. Whitening Effect Pen (LG) containing 3% hydrogen peroxide was used by 20 volunteers using the same protocol. The change in shade (ΔE^(*) color difference) was measured using Shadepilot™ (DeguDent) before, during and after bleaching (2 weeks, 4 weeks and postbleaching 4 weeks). A clinical examination for any side effects (tooth hypersensitivity or soft tissue complications) was also performed at each check-up. The following results were obtained. 1 Both the experimental and control groups displayed a noticeable change in shade (ΔE) of over 2 No significant differences were found between the two group (p>0.05) implying that the two agents have a similar whitening effect. 2 The whitening effect was mainly due to changes in a and b values rather than in L value (brightness). The experimental group showed a significantly higher change in b value thus yellow shade than the control(p < 0.05) 3 None of the participants complained of tooth hypersensitivity or soft tissue complications confirming the safety of both whitening agents 8.3%의 carbamide peroxide를 함유한 펜형 코팅용 미백제인 BlancTis Forte (NIBEC, Seosul & JinCheon)를 실험군으로, 3% hydrogen peroxide를 함유한글 Whitening Effect Pen (LG. Seoul) 제재를 대조군으로 각각 피험자 20명에게 2시간씩 1일 2회 제조사의 지시대로 치아표면에 4주간 적용하도록 지시하고 색조개선 효능과 안전성을 평가하였다. 미백 효과는 미백 전 및 미백 2주, 4주 및 미백 종료 4주 후에 Shadopilot™을 이용하여 색 변화를 측정하였고, 매 내원시기마다 모든 환자는 치수생활력 검사와 치주 및 치태 검사를 통해 부작용 여부 (치아과민증 및 구감 내 연조직의 부작용)를 기록한 후 다음과 같은 결과를 얻었다. 1.실험군 및 대조군의 색 변화량 (ΔE)은 2이상으로 인지할 수 있는 색 변화를 보였으며, 두 제품 간에는 통계적으로 유의한 차이를 보이지 않아 (p > 0.05) 유사한 미백효능을 나타냄을 알 수 있었다. 2,미백효과는 명도의 개선보다는 주로 a. b값의 변화에 의한 것으로 특히 실험군에서 b값의 변화, 즉 황색조의 개선효과가 대조군에 비해 유의성 있게 높은 것으로 나타났다 (p <0.05). 3.치아나 치은의 과민증이나 이상증상을 호소하는 피험자는 없어 두 제품 모두 안전성을 확인할 수 있었다.

Cardiovascular Complications of Novel Anti-Cancer Immunotherapy: Old Problems from New Agents?

Woo-Baek Chung,Jong-Chan Youn,Ho Joong Youn 대한심장학회 2020 Korean Circulation Journal Vol.50 No.9

Many novel anti-cancer therapies have dramatically improved outcomes of various cancer patients. However, it also poses a risk for cardiovascular complications as well. For the novel anti-cancer agent with which physicians does not have enough clinical experiences to determine the characteristics of cardiovascular complications, it is important to assess risk factors for cardiotoxicity before starting anti-cancer therapy. High-risk patient should be consulted to cardiologist before initiating anti-cancer therapy and pre-emptive cardiac function monitoring plan might be prepared in advance. The biomarkers, electrocardiography and echocardiography are useful tools for the detection of subclinical cardiotoxicity during anti-cancer therapy. This review article tried to suggest the cardiac function monitoring strategies for newly encountered potential cardiotoxic anti-cancer agents and to summarize the cardiovascular complications of novel anti-cancer immunotherapies including immune checkpoint inhibitor (ICI) and chimeric antigen receptor (CAR) T-cell therapy. ICIs can cause fatal myocarditis, which usually occurs early after initiation, and prompt treatment with high-dose corticosteroid is necessary. CAR T-cell therapy can cause cytokine release syndrome, which may result in circulatory collapse. Supportive treatment as well as tocilizumab, an anti-interleukin-6 receptor antibody are cornerstones of treatment.

Pathophysiology and preventive strategies of anthracycline-induced cardiotoxicity

( Woo Baek Chung ),( Ho Joong Youn ) 대한내과학회 2016 The Korean Journal of Internal Medicine Vol.31 No.4

Cardiotoxicity is a well-known complication following treatment with anthracyclines. However, they are still widely used in chemotherapy for breast cancer, lymphoma, leukemia, and sarcoma, among others. Patient clinical characteristics, such as age, sex, comorbidities, anthracycline dose and infusion schedule, and the combined anti-cancer agents used, are diverse among cancer types. It is diffi cult to recommend guidelines for the prevention or management of anthracycline-induced cardiotoxicity applicable to all cancer types. Therefore, anthracycline-induced cardiotoxicity remains a major limitation in the proper management of cancer patients treated with an anthracycline-combined regimen. Efforts have been extensive to determine the mechanism and treatment of anthracycline-induced cardiotoxicity. Because cardiotoxicity causes irreversible damage to the myocardium, prevention is a more effective approach than treatment of cardiotoxicity after symptomatic or asymptomatic cardiac dysfunction develops. This article will review the pathophysiological mechanisms of anthracycline-induced cardiotoxicity and strategies for protecting the myocardium from anthracycline.

Do We Really Need to Predict Paravalvular Regurgitation After TAVI With Aortic Valve Calcium Load Before the Procedure?

Woo-Baek Chung 한국심초음파학회 2022 Journal of Cardiovascular Imaging (J Cardiovasc Im Vol.30 No.4

.