Slide Session : OS-IFD-07 ; Infectious Disease : In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus

( Myung Jin Lee ),( Kye Hyung Kim ),( Jong Youn Yi ),( Su Jin Choi ),( Chung Jong Kim ),( Nak Hyun Kim ),( Kyoung Ho Song ),( Pyoeng Gyun Choi ),( Ji Hwan Bang ),( Wan Beom Park ),( Eu Suk Kim ),( San 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1

In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus Myung Jin LEE1, Kye-Hyung KIM1, Jongyoun YI2, SuJin CHOI1, Chung-Jong KIM1, Nak- Hyun KIM1, Kyoung-Ho SONG1, Pyoeng Gyun CHOI1, Ji-Hwan BANG1, Wan Beom PARK1, Eu Suk KIM1, Sang-Won PARK1, Hong Bin KIM1, Nam Joong KIM1, Myoung- Don OH1 Seoul National University College of Medicine, Korea1, Pusan National University School of Medicine, Korea2 Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). No effective antiviral therapy is proven yet, but clinical use of ribavirin (RBV) has been tried. We investigated the antiviral effect of RBV against SFTSV in vitro. Methods: To test for cytotoxicity of RBV, Vero cells were treated with different concentrations of RBV (3.90 to 500 μg/mL, two-fold dilution) and analyzed by cell viability MTS assay 48h post-infection. To determine antiviral activity of RBV against SFTSV, Vero cells were infected with SFTSV strain Gangwon/Korea/2012 at 100 TCID50 (50% tissue culture infective dose) per well in a 96-well plate, and RBV was added at the concentrations showing no or minimal cytotoxicity. Viral RNAs were extracted from the culture supernatants and quantifi ed using one-step real-time reverse transcription- PCR to amplify the partial large segment of SFTSV. Statistical analysis was done by one-way ANOVA with Tukey`s post hoc test. Results: Cytotoxicity due to RBV was not observed at RBV concentration =31.3 μg/ mL. Viral RNAs at 24h post-RBV treatment were reduced with increasing RBV concentrations (1-32 μg/mL), compared with those of mock-treated cells (P <0.01, Figure). Half maximal inhibitory concentration (IC50) of RBV was 3.69 μg/mL at 24h post-RBV treatment. Conclusions: Our study shows that RBV has antiviral effect against SFTSV in a dose-dependent manner. Further studies are required to evaluate the effi cacy of RBV in SFTS.

응급실을 내원한 65세 이상 노인 환자의 분석

김진년,김태훈,강양욱,오명,김상철,김성훈,권계형,남홍우,이홍순,유형준 대한노인병학회 2001 대한노인병학회지 Vol.5 No.3

백당으로 가교된 폴리아크릴산 하이드로겔의 In vitro 점막부착력 평가

이재휘,김선영,이은석,이민석,김형수,최영욱 한국약제학회 2006 Journal of Pharmaceutical Investigation Vol.36 No.2

한국인 갑상선 수질암 환자에서 RET 원종양유전자 점돌연변이 양상

김형훈,김현진,정윤재,민용기,이명식,이문규,김광원,기창석,김종원,정재훈 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.4

연구배경: 갑상선 수질암의 25∼30%는 유전성으로 발현되는데, MEN 2A, MEN 2B 또는 가족성 수질암의 형태로 나타난다. RET 원종양유전자의 점돌연변이가 유전성 갑상선 수질암의 발생에 중요한 역할을 하므로, 진단 당시의 연령이나 가족력 유무에 관계없이 모든 갑상선 수질암 환자나 또는 RET 변이가 발견된 수질암 환자의 가족 구성원들에서 RET 변이 검색을 하여야 한다. 또한 일부 문헌에서 RET 변이의 양상에따라 임상상이 다르게 표현됨이 보고된 바 있다. 이에 저자들은 한국인 갑상선 수질암 환자에서 RET 원종양유전자의 점돌연변이의 양성률을 알아보고, 변이 양상에 따른 임상상의 차이가 있는지를 알아보고자 본 연구를 시행하였다. 방법: 치근 7년간 본원에서 갑상선절제술을 통해 갑상선 수질암으로 진단받은 29예에서 RET 원종양유전자의 점돌연변이 검사를 시행하였다. 29예의 평균연령은 39세(20∼60세)이었고, 남자 7예, 여자 22예 이었다. 이들의 말초혈액에서 genomic DNA를 분리하고, 특이 시발차를 이용하여 RET 원종양유전자의 exon10, 11, 13, 14, 16부위를 증폭하였다. 증폭된 부위를 자동염기서열분석기를 이용하여 직접 분석하였다. 양성으로 나온 경우는 모든 가족 구성원을 대상으로 RET 변이 유무를 검색하였다. 결과: 대상 환자 29예 중 9예 (31%)에서 RET 원종양유전자 점돌연변이가 발견되었다 RET 변이가 발견된 9예 (남자 3예, 여자 6예)의 평균 연령은 33세 (20∼51세)로 RET 변이가 발견되지 않은 20예의 평균연령 42세(24∼60세)보다 의미 있게 적었다. RET 변이가 발견된 9예 중 MEN 2A가 5예, 가족성 수질암이 1예, 그리고 산발성 수질암이 3예이었고, MEN 2B는단 1예도 진단되지 않았다. MEN 2A 5예 중 4예는 exon 11의 codon 634번(C634R 2예, C634Y 2예)에서, 그리고 나머지 1예는exon 10의 codon 618번 (C618R)에서 변이가 각각 발견되었다. 가족성 수질암 1아는 codon 634번(C634W)에서, 산발성 수질암 3예도 모두 codon 634번 (C634y 2예, C634s 1예)에서 각각 변이가 발견되었다. RET변이 양상 또는 위치에 따른 임상상의 차이는 발견할 수 없었다. 결론: 갑상선 수질암 환자 31%에서 RET 원종양유전자의 점돌연변이를 발견할 수 있었다. 유전성 수질암 중 가족성 수질암 1예를 제외하고 나머지 5예는MEN 2A이었다. 저자들의 5예와 지금까지 국내에서 보고 된 7예를 합친 국내 MEN 2A 12예 중 75% (9/12)는 exon 11의codon 634번(C634R 4예, C634y 4예, C634w 1예)에서, 그리고 나머지 25% (3/12)는 exon 10의 codon618번(C618R 2예, C618s 1예)에서 변이가 발견되었다. 국내에서는 codon 634과 codon 618 두 곳에만 국한된 양상이었고, codon 634에서의 C634R 변이는 1/3에서만 나타났다. 비록 본 연구에서는 제한된 환자 수 때문에 변이 양상과 임상상의 관계를 규명할 수 없었지만, 향후 많은 수의 환자를 대상으로 전향적인 연구를 시행하여 genotype-phenotype 관계 규명을 하는 것이 필요하다. Background: Medullary thyroid carcinomas (MTC) have been reported as hereditary in about 25 -30% of cases. The identification of germline mutation in RET proto-oncogene is important in the diagnosis of hereditary MTC, and occurs in three forms: MEN 2A, MEN 2B and familial MTC (FMTC). To evaluate the prevalence of the relationship of RET proto-oncogene mutation and genotype-phenotype was studied in Korean patients with MTC. Methods: Genomic DNA was obtained from 29 patients, with MTC, who underwent a total thyroidectomy, between 1997 and 2003, at the Samsung Medical Center. There were 7 male and 22 female patients, with an average age of 39, ranging from 20 to 60 years. Exon 10, 11, 13, 14 and 16 of the RET proto-oncogene were amplified, with specific primers, using PCR. A sequencing analysis was performed on the PCR product using an automatic sequencing analyzer. Results: Nine of the 29 patients (31%) were identified as having RET mutations. The average age of these 9 patients was 33 years, ranging from 20 to 51, with a female to male ratio of 2. Five patients had MEN 2A and one had FMTC, with the other 3 thought to have non-hereditary (sporadic) MTC. The 4 patients with MEN 2A had RET mutations on codon 634 of exon 11 (2 patients, C634R; 2 patients, C634Y) and the other patient on codon 618 of exon 10 (C618R). One patient with FMTC had a mutation on codon 634 (C634W). Three patients with sporadic MTC had RET mutations on codon 634 (2 patients, C634Y; 1 patient, C634S). However, no genotype- phenotype relationship could be found, due to the limited number of patients. Conclusion: Thirty-one percent (9/29) of the patients with MTC had RET proto-oncogene mutations. Three-quarters (9/12) of the Korean patients with MEN 2A, including another 7 patients reported in 3 papers in Korea, had RET mutations on codon 634 of exon 11 (4 patients, C634R; 4 patients, C634Y; 1 patient, C634W), but a quarter (3/12) had mutations on codon 618 of exon 10 (2 patients, C618R; 1 patient, C618S). Although no relations could be found between the genotypes and phenotypes, extensive prospective studies will be required to verify this (J Kor SOC Endocrinol 18:360-370, 2003).

대황황련해독탕의 사염화탄소 유발 간장해 보호효과 미치 급성독성

김영석,정은아,장종철,양형길,김남재,조기호,배형섭,이경섭,김동현 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2002 東西醫學硏究所 論文集 Vol.2002 No.-

ABSTRACT - This study was performed to evaluate hepatoprotective effect of daewhang-whangryunhaedok-Tang(DWT) on liver injured rats induced by CCI_4 and the acute oral toxicity of it in mice. The activities of serum transaminase(ALT/AST), alkaline phosphatase(ALP) and lactic dehydrogenase(LDH), the levels of serum total cholesterol(TC) and triglyceride(TG), change of liver enlargement, and inhibitory activities of lipid perotidation, catalase and glutathione-S-transfrease(GST) in liver microsome were determined in hepatotoxic rats induced by CCI_4. DWT was significantly reduced the serum ALT, AST, ALP, LDH. TC and TG lecels. And, the increase of lipid peroxidation, decrease of catalase and GST activities in the liver microsome of CCI_4-intoxicated rat were significantly improved by the treatment of DWT. Male and female mice were administered maximum dosages of 5.000 mg/kg b.w. of DWT. After single oral administration of DWT to mice, we observed them daily for 2 weeks.DWT did not induce any toxic signs in the mortalitie, clinical signs, body weight changes, and gross necropsy finfings of mice. Based in these results. It is concluded that DWT may have the hepatoprotective effect on CCI_4 induced hepatotoxicity in rats. Also. DWT may have no side effect and its LD_50 value may be over 5.000mg/kg b.w. in mice.

봉독약침이 류마티스 관절염 환자의 관절 통증, 종창 및 급성 염증 반응에 미치는 영향

이상훈,이현종,백용현,김수영,박재경,홍승재,양형인,김건식,이재동,최도영,이두익,이윤호 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2003 東西醫學硏究所 論文集 Vol.2003 No.-

Objective In order to study the effects of bee venom(BV) on the pain, edema, and acute inflammatory reactant of rheumatoid arthritis(RA) patients. Methods Patients with RA who met the ACR(American College of Rheumatology) 1987 revised criteria for the diagnosis of RA were treated with the BV therapy twice a week for 3 months. Tender Joint counts, swollen joint counts, Visual analog scale(VAS), morning stiffness, ESR. C-reactive protein(CRP) were analyzed before and after BV therapy. Results The results as follows. 1. Tender joint counts in patients after BV therapy were significantly lower than those before BV therapy(9.0±7.9 vs 15± 11.4, p=0.002). 2. Swollen joint counts of the patients after BV therapy were significantly lower than those before BV therapy(50±61 vs 15±23, p=0.001). 3. VAS in patients after BV therapy was significantly lower than those before BV therapy(608± 17.6 vs 380± 159, p=0.000). 4. Duration of morning stiffness in patients after BV therapy was significantly reduced compared with that before BV therapy(119.1± 112.6 min vs 59.0±89.7 min, p=0.009). 5. ESR and CRP were not significantly changed before and after BV therapy, suggesting BV itself could make inflammatory reaction as well as therapeutic effect. Conclusions BV therapy improved tender joint counts, swollen joint counts and duration of morning stiffness in this study, and further study is needed on long-term effect of BV therapy.

클럽 샤프트(Club Shaft) 특성에 따른 골프 스윙(Golf Swing)동작 분석

김성일,김기형,김형수,이현섭,김진욱,안찬규,김희진 한국운동역학회 2002 한국운동역학회지 Vol.12 No.2

본 연구는 클럽 샤프트의 대표적인 재질인 그라파이트(graphite)의 유연한(flexible) 클럽 샤프트(club shaft)의 특성에 따라 피험자가 운동학적(kinematics) 요인이 되는 관절의 각변위, 각속도, 각가속도, 클럽헤드의 속도와 가속도와 같은 변인들이 어떻게 적응하는지 비교 분석하여 보다 효율적인 드라이버 선택에 도움을 주며 샤프트 특성에 따른 신체관절의 움직임에 대한 자료를 제시하고자 하였다. 고속 카메라 2대의 속도는 500fps로 하였고 각 regylar,stiff, x-stiff, 자신의 클럽을 포함 각 4개의 클럽을 사용하여 각 클럽당 3번씩 촬영하였으며 목표방향에서 20m이상 벗어나는 경우의 촬영은 다시 촬영하였다. 본 연구에서는 디지타이징(digitizing)을 신체 9개 마커는 강체로 가정된 클럽과 신체분절 모델로 정의하였으며 2 대의 카메라(500fps)로부터 얻은 avi화일을 컴퓨터에 저장하고 자료로부터 Butterworth 6th order recursive digital filter를 사용하여 1차 자료를 smoothing 하고 DLT를 이용하여 3차원 좌표를 구성하도록 한다. 좌표값을 얻기 위하여 kwon3d v3.0을 이용하였다. 본 실험은 피험자 스스로 클럽의 특성에 따라 스윙의 속도를 달리 하기 때문에 스윙의 시간이 달라지며 어느 정도 클럽이 강성에 따라 스윙시간이 빨라지는 결과로 나타났다. 이것은 피험자가 샤프트가 강성(stiffness)에 따라 스윙 속도를 빨리 하게 되는 원인이 되는 것으로 생각된다. 어깨의 각변위는 클럽이 regular의 경우 임팩트에서 각속도를 계속 유지하고 있으며 stiff, x-stiff의 경우에는 어깨의 움직임이 임팩트에서 급격하게 감소되는 것을 알 수 있다. 이것은 팔의 동작과 클럽의 힘을 크게 하기 위한 동작으로 생각된다. 어깨 각속도는 클럽이 stiff할수록 각속도가 큰 감속하는 것으로 나타났다. 손목속도는 regular 클럽의 경우 손목의 감속이 늦게 되고 임팩트에서 손목의 감속이 적게 하는 것으로 나타났으며 stiff와 x-stiff의 클럽에서 임팩트 시에 순간적인 감가속으로 인해 클럽의 속도를 증가시키고 있다. 임팩트 시에 손목의 감가속은 클럽헤드의 임팩트 시 속도를 증가시키는 결과를 보였다. 클럽헤드는 regular 클럽이 임팩트전에는 속도 증가가 커지는 결과와 일치된 결과를 보이고 있다. The purpose of this study was to find the rational method to analyze golf swing with specific property of club shaft. Three subjects were filmed by two high speed digital cameras with 500fps. The phase analyzed was downswing of each subject. The three-dimensional coordinates of the anatomical landmarks were obtained with motion analysis system Kwon3d 3.0 version and smoothed by lowpass digital filter with cutoff frequency 6Hz. From these data, kinematic and kinetic variables were calculated using Matlab(ver 5.0) The variables for this study were angular velocity and accelerations, which were calculated and following conclusions have been made : 1) Golf swing time of stiff club is faster than that of regular club. 2) In shoulder joint motion of swing with the stiff club, x-stiff showed mort rapid negative acceleration than that of regular club. 3) In regular club, the velocity of club head would be more effective velocity, which was increasing, than those of other clubs before impact. 4) In wrist joint motion of swing with stiff club, x-stiff club showed faster than regular club in the downswing and impact more rapid negative acceleration.

부산지역 수돗물과 지하수의 중금속 농도

김준연,손지언,김형수,김두희,원미숙,김인식,이혜령 동아대학교 산업의학연구소 2000 산업의학연구소 논총 Vol.- No.5

This study investigated mean airborne CO concention of 15 workplaces, suspected of CO exposure and conducted self-reported questionnaire completion and indirect COHb concentration measure using Micro II Smokerlyzer to healthy 702 adult subjects from 1999 May to 1999 September in order to find a relation of CO exposure and occupational factors, socioeconomic factors, and health related behaviors and confirm the related conditions in the screening test for CO exposure. The results of this study were summarized as follows : 1. In the CO exposed and non exposed group, COHb concentrations of the smokers were 2.55±0.96% and 2.21±0.97% and that got a statistically significant difference, There were not statistically significant differences in the age and total smoking index. Passed times after the last smoking, Working time/day, and working duration were statistically significant difference (p〈0.05). 2. In the CO exposed and non exposed group, COHb concentrations of non-smoking group were 0.94±0.35% and 0.68±0.47% and that got a statistically significant difference. There were not statistically significant differences in the age and working duration but Working time/day was a statistically significant difference(p〈0.05). 3. In the CO exposed group, r-square of multiple regression of the smokers was 38.5 % and passed time after the last smoking, working time/day, and job category were statistically significant differences (p〈0.05). And r-square in the CO non-exposed group was 38.3 % and age, passed time after the last smoking, and total smoking index were statistically significant difference. 4. In the CO exposed group, r-square of multiple repression of the non-smokers was 66.3% and job category and airborne CO concentration were statistically significant differences(p〈0.05). But r-square of non-smokers in the CO non-exposed group was 1.0% and there was not a statistically significant difference(p〈0.05). 5. In the smokers of CO exposed and non exposed groups, relation of COHb concentration and passed time after the last smoking was expressed as exponential function, Y = 2.9182e-0.0083x and r-square of this function was 37.4%. Therefore it was more than 150 minutes that passed time after the last smoking was when COHb concentrations were measured as less than 1%. In conclusion, variable, that was statistically significant to COHb concentraion in the both CO exposed and non-exposed smokers, was a passed time after the last smoking. We suggest that you have to restrict the smoking of smokers at least 150 minutes in the exposed and non exposed group before COHb concentration measure in order to exclude smoking effects

유제놀에 의한 즉시형 알레르기 반응의 억제

김상현,신태용,김형룡,이영미,이은희,신보경,김윤철,안년형,김형민 우석대학교 의약품개발연구소 1996 藥學硏究誌 Vol.1 No.-

The current study evaluates the capacity of eugenol to regulate immediate allergic reaction by control of histamine release. Administrations of eugenol (1 M/kg. i.p.) at 60 min before and 5.10 min after the compound 48/80 treatment (8 mg/kg.i.p.) were shown the mortality rates as 0.44.4. and 77.8%. respectively. A 60 min before administered group revealed a singificant inhibition of serum his-tamine release compared with those of 5 and 10 min after the compound 48/80 injection. Eugenol (6-48mM) was also showed a dose-dependent activity on the compound 48/80-induced histamine release from the highly purified population of Alcian Blue-positive peritoneal mast cells. These results indicate that in vitro treatment with exogenous eugenol inhibited the active response of mast cell populations and modulated its characteristics.

40세 이하 관상동맥 질환자에서 장기적 임상 관찰

이승욱,정명호,박종철,박형욱,조상희,김원,김계훈,이상현,강경태,조장현,김남호,김건형,안영근,조정관,박종춘,강정채 全南大醫大 2001 전남의대학술지 Vol.37 No.2