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 추계학술대회 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.

人 諸臟器 Alkaline Phosphatase Isoenzyme의 電氣泳動 및 定量

金在植,金京善,金重明,金榮泰,蔣卓仙,李鉉基 慶北大學校 醫科大學 1980 慶北醫大誌 Vol.21 No.2

著者들은 家兎와 人體로부터 採取한 血淸과 諸臟器組織을 使用하여 ALPI 電氣泳動像을 觀察하고 生化學的 定量法을 利用하여 ALP의 活性度를 測定試圖하였으며 臟器特異性 沮害因子에 對한 影響을 觀察하였다. 家兎 血淸 및 諸臟器組織 ALPI電氣泳動에서 血淸은 ±의 活性度를 가진 α2와 α2/β分劃을 나타내었으며 肝組纖은 血淸보다 빠른 移動度를 가진 ??의 α_1과 α_2分劃을 나타내었다. 그리고 肝, 骨, 腎 淋巴腺, 脾臟 및 腸組織에서는 顯著하게 높은 活性度를 나타내는 各各 서로 相異한 分劃을 볼 수 있었으며 人體諸 臟器와大體로 類似하였으나 家兎 血淸의 ALP는 사람에서 와는 다르게 肝組織의 分劃과 一致하지 않고 오히려 骨組織과 더 잘 一致되는 것 같았다. ALPI 活性度에 있어서 家兎의 諸臟器는 生化學的 定量法으로 腎 ALP의 活性度가 49.5B.L. units로 다른 臟器組織에 비하여 顯著하게 높았으며, 그 다음은 脾臟, 脊椎骨, 肝, 肺淋巴腺 및 脾 順으로 높은 活性度를 나타내었으며 人體에 있어서는 胎盤, 骨, 小賜, 脾臟, 肝 및 腎臟의 順으로 높았다. 臟器 特異性 沮害因子에 對한 影響에 있어서 胎盤分劃은 特有하게 耐熱性을 나타내었고 보다 urea低抗性이며 肝分劃은 neuraminidase에 對하여 移動度의 遲延을 招來하였다. The studies upon cellulose acetate microzone electrophoretic patterns, quantitative estimation and effects of organspecific inhibitor on ALP isoenzyme of rabbit and human sera and various organ tissues were performed. On electrophoretic pattern the tissue ALP from the liver bone kidney lymph node spleen and intestine showed the characteristic fraction of high activities. The electrophoretic mobility of rabbit serum ALP was not correspond to the liver ALP as observed in human serum and it appeared to be rather corresponded to the bone ALP, which seemed to be the origin of ALP in serum of rabbit. In the quantitative measurement of tissue ALP activity the kidney ALP showed the highest level and the activity of the skeletal muscle ALP was the lowest(1.5 B. L. units), while higher activities were observable in placenta, bone, intestine, spleen, liver and kidney in order. On the effect of organ specific physico chemical agents the placental ALPI was highly stable to the heat and relatively resistant to urea while other organ ALPI were on the contrary. The neuraminidase seemed to effect to the motility of liver fraction.

담낭 방선균증 1예

김형수,정진원,김양수,우준희,송현순,류지소,김명환,김남중 대한감염학회 2003 감염과 화학요법 Vol.35 No.5

저자들은 우상복부 통증과 소화불량을 주소로 내원한 83세 여자 환자에서 국내 최초로 담낭 방선균증을 진단하고 치료 관찰 중으로 이에 문헌고찰과 함께 보고하는 바이다. Actinomycosis is a chronic suppurative and granulomatous disease, characterized by abscess formation, tissue fibrosis, and draining sinuses. Actinomycosis of the gallbladder is very rare and has not yet been reported in Korea. We report a case of actinomycosis of the gallbladder in an 80-year-old women with history of cholelithiasis for 3 years, preoperatively misidentified as gallbladder cancer. Histologic section of the gallbladder showed Gram-positive branching bacilli compatible with actinomyces. After cholecystectomy, the patient received intravenous ampicillin for 4 days, followed by amoxicillin for 4 months thereafter.

간세포암환자에서 간동맥 화학 색전술 후 발생한 리피오돌에 의한 폐렴 1예

김소이,김유리,허현미,배서은,이명원,최윤정,김고흔,김태헌,유 권,문일환 이화여자대학교 의과대학 2009 EMJ (Ewha medical journal) Vol.32 No.2

Hepatocellular carcinoma(HCC)is one of common causes of cancer-related death in Korea where the majority of HCC patients were Hepaitc B virus(HBV)carriers and have cirrhosis. Transarterial chemoembolization(TACE)is commonly applied to the treatment of multinodular HCC in Korea and careful selection of candidate is important for the risk of various side effects. Besides common side effects as fever, nausea, abdominal pain and elevation of liver enzyme, TACE may predispose to hepatic failure, ischemic cholecystitis, pulmonary embolism, cerebral embolism and pneumonitis. In previous studies, some cases of pulmonary and cerebral embolism cases were reported but lipiodol pneumonitis after TACE was rarely reported. A 65-year-old woman with a multinodular HCC associated with HBV infection, was treated with TACE. Seven days after the procedure, nonspecific respiratory symptoms such as dyspnea and dry cough developed. Chest X-ray and chest computed tomography showed diffuse ground glass opacities in whole lung fields, suggestive of lipiodol pneumonitis. After several days of supportive care with steroid administration, radiologic abnormalities and subjective symptoms were much improved, considered that the disease was compatible with lipiodol pneumonitis.

Thiamine결핍 유도후 쥐 전뇌의 성상교세포 Glial Fibrillary Acidic Protein(GFAP) 면역화학 활성도에 대한 변화

김승현,김희태,김주한,김명호,황세진,김명권,백태경 대한신경과학회 1999 대한신경과학회지 Vol.17 No.1

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).

한국인 알코올 의존 환자에서 알코올 대사 효소 유전자형 빈도의 남녀 차이

김성곤,김철민,이덕기,황인복,이현숙,김성연,전은숙,송영상,박제민,최병무,김명정 大韓神經精神醫學會 2005 신경정신의학 Vol.44 No.2

Objectives : There are a number of preceding epidemiological studies reporting gender differences in the genetic etiology of alcohol dependence. The author investigated gender difference in the frequencies of ADH2 and ALDH2 genoypes between the patients with alcohol dependence and normal control. Methods : The subjects were 141 alcohol dependent patients (104 males, 37 females) and 138 normal control (79 males, 59 females). The frequencies of 1/1 and 1/2+2/2 (2+ afterward) genotypes for ADH2 and ALDH2 were investigated in male and female between alcohol dependence and normal control group. DNA was extracted from WBC in peripheral venous blood and PCR-RFLP method was used out for genotyping. Results : First, the frequency of ADH2 1/1 genotype was significantly higher in alcohol dependent patients than normal control in both genders. Second, while there was no gender difference in the frequency of ADH2 1/1 genotype in normal controls, in the patient group however, the frequency was significantly higher in females than males. Third, in male subjects with alcohol dependence, the frequency of ALDH2 1/1 genotype was significantly higher than in male normal control subjects. On the other hand, in female subjects with alcohol dependence, the frequency of ALDH2 2+ genotype was significantly higher than in female normal control subjects. Conclusion : These results suggest that while the risk of alcohol dependence is predominantly affected by ALDH2 1/1 geno-type in male, the female ADH2 1/1 genotype is mainly associated with the risk of alcohol dependence. This means that there are gender differences in the genetic etiology of alcohol dependence.

정상과 갑상선 종양조직에서 사람 IGF-I 유전자의 발현

김성운,장현하,박상미,김덕윤,우정택,양인명,김진우,김영설,김광원,고석환,홍성화,최영길 경희대학교 유전공학연구소 1993 遺傳工學論文集 Vol.5 No.-

Many of the growth-promoting properties of growth hormone(GH) are mediated by insulin-like growth factor-I(IGF-I), a highly conserved circulating 70-amino acid peptide. Recent studies have shown that multiple mechanisms influence IGF-I gene expression, including transcription from two promoters, alternative RNA splicing, and variable polyadenylation. In thyroid tissue, thyroid stimulating hormone(TSH) and IGF-I are the most possible candidates for follicular cell proliferation and hypertrophy. Actually IGF-I had autocrine and paracrine effect for tissue growing. We prepared thyroid tumor tissue mRNAs using single step method for detecting IGF-I levels according to different tissues, i.e., thyroid adenoma or papillary thyroid carcinoma. We used Northern blot analysis for IGF-I mRNA and RNase protection assay (RPA) for IGF-I transcription start sites. For Northern blot, we used whole human IGF-I cDNA as a DNA probe and for RPA, we used IGF-I exon 1 containing noncoding promoter 1 as a riboprobe. We got good RNA bands from Northern blot analysis around 1 kb (IGF-IA) and 7.5 kb (IGF-IB) region. To clarify the amount of both IGF-IA and IB mRNAs, we measured autoradiographied signal of IGF-I mRNAs bands using densitometer. In IGF-IA signals, there's no change among liver and thyroid tissues, but in case of IGF-IB mRNA bands, the signal was markedly increased in thyroid carcinoma tissues than that of normal thyroid tissue (85% vs 14%). In the study of RPA, all thyroid tissues used the same transcription start sites as those of liver's. We concluded that that this different regulation of IGF-I mRNA was originated from tissue specificity. That meant some tissue specific transcription factor/s were related to tissue IGF-I expression.

사회적 음주자에서 날트렉손 투여가 급성 음주 반응에 미치는 영향

김종현,김성곤,신성현,박제민,김명정 大韓神經精神醫學會 2004 신경정신의학 Vol.43 No.6

Objectives : We investigated the effects of naltrexone on acute alcohol response, stimulant and sedative, in healthy social drinkers using two doses of alcohol intake. Methods : Twenty four healthy male medical students were voluntarily participated. The experimental method was Cross-over design, Subjects received 25 mg/day or 50 mg/day of naltrexone on the experimental days. Biphasic Alcohol Effects Scale (BAES), alcohol craving, and blood alcohol concentration (BAC) were measured before drinking and at 15, 30, 45, 60, 90,and 120 min after drinking. Results : 1) Group of 0.6 mg/kg of alcohol intake. When the scores of stimulative subscale of BAES were compared bet-ween the naltrexone and control group, the scores were significantly lower in the naltrexone group at 15 and 90 min after drinking. Alcohol induced sedative effect was significantly higher in the naltrexone group at 90 min after drinking. The alcohol induced alcohol craving at 45 and 60 min after drinking was significantly lower in the naltrexone group as compared to the control. 2) Group of 0.3 ing/kg of alcohol intake. The alcohol induced stimulative effect evident in the control group seen in the time span of 15 to 45 min after drinking was not seen in the naltrexone group. The increase of alcohol induced alcohol craving noticed at 30 min after drinking in the control group was not seen in the naltrexone group. BAC at 15 min after drinking was lower in the naltrexone group compared to the control. Conclusion : Naltrexone is suggested to attenuate stimulative effect, to intensify sedative effect, and to block alcohol induced alcohol craving. These triple actions might be utilized for treatment and prevention of relapse of alcohol dependence.

통계적 에너지 해석법에 의한 선박소음 예측프로그램 개발에 관한 연구

김사수,현명환,김명현,이도경 부산대학교 1994 生産技術硏究所論文集 Vol.47 No.

선박에 있어서 소음은 공기중 소음(Airborne Noise), 구조전달 소음(Structureborne Noise), 수중방사 소음(Waterborne Noise)으로 나눌 수 있다. 선박소음을 예측하는 과정에서 고체소음전달해석은 직접적으로 예측결과의 정도에 영향을 미치므로 이에 대한 적절한 해석 기법의 개발이 요구된다. 본 연구에서는 고체음 전달해석을 수행하기 위하여 통계적 에너지 해석법(Statistical Energy Analysis-SEA)의 방법에 의해 고체소음 전달 손실을 이론적으로 예측하고 실험모델을 이용하여 각종 파라메터 추정 및 그에서 얻은 실험치와 비교분석을 함으로서 그 타당성을 확인하고 이의 결과를 보다 복잡한 선박구조물에 적용하여 고체소음 수준을 예측하는 방법으로서의 가능성을 확인하고자 한다. In order to build a quiet and comfortable ship, the noise levels on board ship must be predicted at early design stage. Statistical Energy Analysis(SEA) developed by R.H.Lyon has been well known to be the most useful frame work to study the energy flow of noise and vibration in structure. This paper applied this theory to predict the transmission loss of structureborne noise of model structure and have developed computer program. Components constructing model structure have been all considered as SEA elements. To examine the accuracy of the program, experiments were carried out on model structure with a white noise as a noise source. And we also estimated the SEA parameters from the model structure. The results of comparison between the calculated and measured data have shown good agreement.