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.

조혈모세포이식 환자에서 침습성 진균 감염에 대한 이트라코나졸 액과 플루코나졸 시럽의 예방 효과 : 전향적, 무작위, 비교 임상시험

최수미,이동건,최정현,박선희,엄기성,김유진,김희제,민창기,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2005 감염과 화학요법 Vol.37 No.2

목적 : 조혈모세포이식 환자에서 호중구 감소 기간 동안 이트라코나졸 액(ITZS)과 플루코나졸 시럽(FCZS)의 진균 감염에 대한 예방 효과를 전향적으로 비교해 보고자 하였다. 재료 및 방법 : 2001년 8월부터 2002년 6월까지 가톨릭 조혈모세포이식센터에 입원하여 동종 조혈모세포이식을 받은 만 18세 이상의 환자들을 각각 ITZS와 FCZS군으로 무작위 배정하여 침습성 진균 감염 발생과 약제 관련 부작용을 전향적으로 조사하였다. 결과 : ITZS군에 40명, FCZS군에 38명이 배정되었고, FCZS군 환자의 평균 나이가 더 많았다. 시험 약제 평균투여기간은 ITZS군 16.4일, FCZS군 21.9일로 ITZS군이 더 짧았다. 이는 ITZS군에서 소화기 부작용으로 인한 약제 중단이 더 많았기 때문으로 보인다. 시험 약제 투여 후 총 빌리루빈 수치의 유의한 증가가 관찰되었으나, 약제 관련 부작용은 모든 환자에서 가역적이었다. 호중구감소 기간동안 표재성 진균 감염은 두 군에서 모두 발생하지 않았고, 침습성 진균 감염은 ITZS군 5명(12.5%), FCZS군 8명(21.1%)으로 FCZS군에서 많았으나, 통계학적으로 유의하지 않았고, 사망률에도 유의한 차이는 없었다. 결론 : 침습성 진균 감염에 대한 이트라코나졸 액과플루코라졸 시럽의 예방 효과에 유의한 차이는 없었으나, 앞으로 더 많은 환자를 대상으로 잘 짝지어진 대조군 연구가 필요할 것으로 보인다. 부작용 중 간독성과 관련하여 이식시 투여되는 여러 약제들과의 상호작용에 대한 연구도 필요할 것이다. Background : Though fluconazole is widely used for antifungal prophylaxis, it is ineffective against mould infections including Aspergillus species. Itraconazole has a broader spectrum than fluconazole but the capsule form shows erratic bioavailability in neutropenic patients. In this study, we compared itraconazole oral solution (ITZS) with fluconazole syrup (FCZS) for the prevention of invasive fungal infection (IFI) in allogeneic hematopoietic stem cell transplant recipients. Materials and Methods : Adults receiving allogeneic hematopoietic stem cell transplantation (HSCT) from september 2001 to June 2002, were randomly allocated to either the ITZS group or the FCZS group. We prospectively evaluated the safety and efficacy of each drug. Results : Out of 78 patients (40 patients in the ITZS group and 38 patients in the FCZS group) who were eligible for this study, 37 patients completed the course of prophylaxis without any evidence of IFI. The mean duration of prophylaxis was 16.4 days for the ITZS group and 21.9 days for the FCZS group (P<0.006). Drug-related adverse events occurred in 28 patients (70.0%) and 19 patients (50.0%) in the ITZS group and the FCZS group, respectively. Common adverse events of ITZS were nausea, vomiting, and diarrhea. Drug-related reversible hepatotoxicity occurred in 4 patients in the ITZS group. There was a significant elevation of total bilirubin level in the ITZS group. The incidence of suspected IFI occurred in 5 patients (12.5%) who received ITZS, compared with 8 (21.1%) who received FCZS (P=0.372). There were no proven IFIs or superficial (oral/vaginal) fungal infections in both groups. Overall mortality was not different between the two groups (2.5% in the ITZS group versus 5.3% in the FCZS group, P=0.610). Conclusion : ITZS and FCZS showed similar protection against IFI during pre-engraftment period. Poor tolerability due to gastrointestinal troubles of ITZS might limit its success as prophylactic therapy. Well matched controlled study with large number of patients will be required in the future.

호흡기계 감염에 대한 Broncho-vaxom^�의 임상적 효과

최호경,이건수,서종진,정용헌 충남대학교 의과대학 지역사회의학연구소 1990 충남의대잡지 Vol.17 No.1

Thirty children with respiratory tract infections, 17 with acute and chronic bronchitis, 5 with sinusitis, 4 with rhinitis, 3 with asthma, 1 with tonsillitis, were given Broncho-vaxom^?? one capsule per day on an empty stomach for 1 month to evaluate the efficancy of the drug on acute and chronic respnatory tract infections in children. After the medication, we observed the changes of clinical symptoms, and side effects. The results are as follows; 1. The symptomatic improvements after Broncho-vaxom^?? administration were as follows; expectoration(80%), fever(72%), rhinorrhea(67%), hoarseness(67%), and coughing(65%). 2. Combined treatment with antibiotics was necessary in 19 cases(63%). 3. The degree of response were observed as mild improvement in 3 cases(10%), moderate improvement in 13 cases(84%), and excellent improvement in 1 cases(47%). 4. The side effect of Boncho-vaxom was not observed during this study.

시ㆍ도별 체육시설과 경기성적의 비교분석

최종수,유인형 忠北大學校 平生體育硏究所 1991 平生體育硏究所 論文集 Vol.5 No.-

Ⅰ) Purpose The purpose of this is efficiency study for two basic methods which are criteria of estabishing physical education's system, physical basic condition in order to secure physical activities. One of two methods which are criberia of securing physical education's system worldwidly is to consider the area of facilities per one, according to golden plan method in German, and the other is to consider the number of physical education's facilities which is needed to satisfy the demand of local physical populations by central council of physical recreation in England. Among these, I'll try to examine the method which is effectively more proper in Korea by events. Ⅱ) Method By dividing the whole nation into 14 administrative districts, 25 kinds of events studied, which is based on the data of administrative organ accounts the number of faclities in each district and the occupation rate of nation. After getting the everage of both, through relative comparing, comparative superior group of the number in the view of facilities and comparative superior group of the area in the view of facilites are divided. And by contrasting in game score of National Sports Meet for last 4 years according to districts, superior or inferior of game score among groups are given. Ⅲ) Results (1) As game score in comparative superior group of the area in the view of facilities is better, it occupys 72% of the searched events. On the other hand, comparative superior group of the number in the view of facilities occupys only 24% on the searched events. Therefore it shows that securing sufficient place for physical education by a large scale of facilities is necesary in order to improre national physical education and competition ability. (2) For the criteria of securing the physical education's facilities in district, golden plan method in German is more efficient for improving competition ability, C.C.P.R method in England is only the best alternative plan, when they have difficulty in securing the narrowing ground. (3) To put it concretely, some events including football, table tennis, wrestling, weight lifting, archery, bowling seems to be possible to use C.C.P.R method.

조혈모세포이식 환자에서 발생한 Cytomegalovirus 질환의 특징 : 일개 대학변원에서 최근 10년간의 경험

최수미,이동건,박선희,김시현,김유진,민창기,김희제,이석,최정현,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2009 감염과 화학요법 Vol.41 No.1

Background : Studies on cytomegalovirus (CMV) diseases in Korean hematopoietic stem cell transplant (HSCT) recipients are lacking and do not reflect the recent trends of advances and changes. Therefore, we tried to analyze the clinical features of CMV diseases in HSCT recipients over the past 10 years at a tertiary university hospital in Korea. Methods : Retrospective review of medical records was done for all adult HSCT patients who received transplant at the Catholic HSCT Center from January 1998 to January 2008. Results : Forty-four cases (2.2%) of CMV diseases were identified. CMV pneumonia was diagnosed in 17 patients, retinitis in 16 patients, enterocolitis in 7 patients, esophagitis 1 patient, gastritis in 1 patient, duodenitis in 1 patient, and hepatitis in 1 patient. The median onset of symptom was 90 days after transplantation. Late CMV diseases accounted for 47.7%. CMV related death varied from 0 to 58.8% according to the involved organ. CMV retinitis was diagnosed relatively later in the course of transplantation mostly in patients who had chronic graft versus host disease (GVHD). On the contrary, CMV enterocolitis mainly occurred in patients who suffered from acute GVHD. The overall concurrent CMV reactivation was documented to be 63.6%: the concurrent CMV reactivation was observed only in 37.5% of patients with retinitis. Conclusions : We observed some differences in the pattern of CMV disease manifestation according to the involved organ and reconfirmed the fact that CMV pneumonia is the most common and fatal disease in HSCT recipients. Additionally, CMV retinitis was not uncommon in HSCT recipients. Since specific marker does not exist in predicting retinitis, regular ocular examination should be done thoroughly, especially in patients with chronic GVHD.

국내 조혈모세포이식 환자에서 Human Cytomegalovirus gB 유전형의 분포와 질환과의 연관성 : 예비 보고

최수미,김진희,이동건,박선희,최정현,유진홍,박철민,이종욱,민우성,황응수,신완식,김춘추 대한감염학회 2007 감염과 화학요법 Vol.39 No.2

목적 : 사람 거대세포바이러스(Human cytomegalovirus, 이하 HCMV) glycoprotein B (gB)는 UL55 유전자에 의해 부호화되는 당단백으로, UL55 유전자의 염기서열변화에 따라 4가지 유전형으로 나뉜다. 본 연구에서는 국내 조혈모세포이식 환자들에서 HCMV gB 유전형의 분포와 그 특성을 알아보고, gB 유전형에 따라 특정 HCMV 질환 발생과 연관이 있는지 그 임상적 의미를 분석해 보고자 하였다. 재료 및 방법 : 동종 조혈모세포이식 환자 52명의 혈액검체 94개에 대해, Chou 등이 제시한 방법에 따라, 먼저 UL55 유전자 부위를 nested PCR로 증폭한 후, RsaI과HinfI으로 Restriction fragment length polymorphism(RFLP) 분석을 시행하였다. 결과 : gB type 1은 73.1% (38/52), gB type 2는 13.5%(7/52), gB type 3는 1.9% (1/52), gB type 1과 type 2에 의한 혼합감염은 9.6% (5/52)로 나타났다. gB type 4는 관찰되지 않았다. 1명(1.9%)에서 gB 유전형을 결정할 수 없었는데, RFLP 패턴으로 보아 Trincado 등이 제시한 gB type 7에 해당하는 것으로 생각되었고, 이 새로운 아형에 대해서는 현재 염기서열 분석 중이다. 52명 중 5명(9.6%)에서 HCMV 질환이 발생하였고, 3명에서 HCMV 폐렴, 1명에서 망막염과 위장관염, 나머지 1명에서 망막염이 발생하였다. 5명 중 HCMV 질환과 관련하여 사망한 예는 없었고, 감염된 HCMV는 모두 gB type 1이었다. HCMV gB유전형과 HCMV 질환 발생 사이에 유의한 연관성은 없었고, 단일 주에 의한 감염과 혼합감염에 따른 HCMV 질환발생 사이에도 유의한 연관성은 관찰되지 않았다. 자료 분석 중 gB type 2에 감염되어 있던 환자에서 gB type 1에 재감염 되면서 발열, 간효소 수치 상승 및 pp65 HCMV 항원혈증이 나타난 예가 있었다. 결론 : 연구결과 gB type 1이 아주 우세하고, gB type 4는 검출되지 않았으며, 혼합감염의 빈도가 비교적 낮은 분포를 보였다. 이는 외국의 보고와는 다른 국내 조혈모세포이식 환자에서의 독톡한 감염 양상으로 추정된다. 본 연구에서 HCMV gB 유전형과 질환 발생과의 연관성을 밝힐 수는 없었으나, HCMV 유전형에 대한 연구는 바이러스 감염의 발병기전이나 전파 경로 및 양식과 같은 역학적 연구에 중요한 자료가 될 것이다. 현재 더 많은 수의 조혈모세포이식 환자를 대상으로 연구가 진행 중에 있으며, 앞으로 다른 질환군의 환자나 건강한 잠복 감염자에서의 추가 연구가 필요할 것으로 생각된다. Background : Human cytomegalovirus (HCMV) glycoprotein B (gB) is the major envelope glycoprotein, encoded by the UL55 gene. Based on sequence variation in the UL55 gene, HCMV can be classified into four gB genotypes. Previous studies have suggested an association between HCMV gB genotypes and clinical outcome in the immunocompromised hosts. The goal of this study was to determine the distribution of HCMV gB genotypes and the effect of gB genotype in the developement of HCMV diseases in hematopoietic stem cell transplant (HSCT) recipients in Korea. Materials and Methods : DNA was extracted from 94 blood specimen of 52 allogeneic HSCT recipients with HCMV infection. HCMV gB genotype was determined using polymerase chain reaction to amplify a region of UL55, followed by restriction fragment length polymorphism (RFLP) analysis based on RsaI and HinfI digestion. Results : The distribution of gB types were as follows: gB1, 73.1% (38/52) of patients; gB2, 13.5% (7/52); gB3, 1.9% (1/52) and mixed infection (gB1 and gB2), 9.6% (5/52). While gB4 was not detected, a new genotype (described as gB7 by Trincado et al, 2000) was identified on the basis of their RFLP pattern. During average 708 days’ follow up period, HCMV diseases developed in 5 patients. All of them had gB1 genotype. There was no statistically significant association between the incidence of HCMV diseases and the gB genotypes. Re-infection with gB1 strain was detected in one patient who had been previously infected with gB2. This episode was associated with fever, elevated liver enzyme and positive antigenemia. Conclusion : HCMV gB1 was the dominant genotype and no gB4 was detected in allogeneic HSCT recipients in Korea, which is an unique pattern compared with the previous reports. Although we can not find significant association between the HCMV diseases and the gB genotypes, genotyping of HCMV will serve in the study of pathogenesis and transmission of this virus in transplant patients. Further study is underway with large study population.

사회복지에 있어서 자원봉사활동의 실태와 활성화 방안

최용호,김종환,박근수,노병수 朝鮮大學校 社會科學硏究所 2004 社會科學硏究 Vol.25 No.1

황산이온 포착용 보호컬럼을 가진 이온 크로마토그래피에 의한 선택적인 음이온의 동시검출

최용욱,김종훈,김미경,최윤정,이수영 전주대학교 자연과학종합연구소 1997 전주대학교 자연과학연구소 학술논문집 Vol.10 No.3

Simultaneous detection method for measuring anions in drinking water except sulfate ion was developed by suppressed ion chromatography. Eluent with existing composition between carbonate and bicarbonate made the separation of early eluting anions poor. Therefore, it is necessary to use weaker eluent to increase the resolution of them. However, this caused elution time of sulfate ion to take long, consquantely, total pinning time was more than 60 minutes. In order to resolve this problem by use of column switching with guard column for trapping sulfate ion, the resolution of the rest 8 anions was enhanced, total running time was also shortened within 10 minutes. Usage of eluent with existing composition made possible determination of sulfate ion on guard column within 4 minutes. Calibration curves of 8 anions represented linearity of better than 0.999 and detection limits by this method of all the anions considered were between 0.04 and 0.002 mg/L

T cell epitope 차폐에 의한 b_(4) peptide 면역응답방응에 대한 연구

최정순,이희종,공수강,리투,류용구,김효준 한양대학교 이학기술연구소 2005 이학기술연구지 Vol.8 No.-

Apo B-100 is a constitutive component of low density lipoprotein (LDL) of which functions in packaging, transport and absorption of lipids Extortive binding of anti B_(4)-antibody onto the Apo B-100 should inhibited the functions of Apo B-100 Previously we had showed that the peptide B_(4) induced antibodies recognized Apo B-100 and thus elicited anti-obesity effect In this study we compared the efficacy of antibody inducing immune responses by introducing additional peptides fused to the C-termninal of B_(4) peptide We constructed TB_(4) hybride peptide of B_(4) with preS2 of HBV and B_(4)N another epitope orientation of chimeric TB_(4) Among these three artificial peptides B_(4)N was the most efficient inducer of the antibody against B_(4) These result explains that the B cell epitope and T-helper cell epitope orientation is very important factor to determine the antigenicity to humoral immunity. Apo B-100은 LDL에서 지방을 포장, 흡수, 운반하는 기능을 수행하는 단백질이다. Apolipoprotein B-100(Apo B-100)에 대한 특이 항체의 결합은 LDL의 정상 기능을 방해한다. 선행 실험에서 Apo B-100의 모조 펩타이드인 B_(4)가 Apo-B-100을 교차 인식하는 항체를 유도하고, 비만 억제 효과를 나타내는 것으로 밝혀졌다. 본 연구에서 B_(4)펩타이드의 C-terminal부분에 펩타이드를 융합, 첨가하므로 면역반응에서 항체유도의 면역응답반응에 어떠한 효과를 나타내는지 비교해 보고자 하였다. B_(4)펩타이드의 N-말단에 HBV의preS2 펩티드를 융합시킨 B_(4)T의 N-말단데 또다른 B세포 에피도프 펩티드를 융합시킨 B_(4)N을 작성하였다, 세종류의 하이브리드 펩타이드 중에서 B_(4)N이 B_(4)에 대한 항체유도능이 가장 효율적이다,. 이상의 결과로 B cell epitope과 T-helper cell epitope의 방향성이 체액성 면역 반응에서 항원유도능을 결정하는 중요한 요소임을 확인하였다.

간척지 중염답에서 유수형성기 염처리에 따른 벼 생육 및 수량 변화

최원영,이규성,고종철,김상수,김태수 한국국제농업개발학회 2003 韓國國際農業開發學會誌 Vol.15 No.3

본 연구는 새계화벼를 공시하여 간척지 중염답(0.3~0.4%)에서 관개수 염농도에 따른 생육 및 수량성을 검토하고자 유수형성기에 5일간 염수를 처리하여 시험한 결과를 요약하면 다음과 같다. 1. 관개수 염분농도가 높을수록 벼 출수는 1~2일 지연되었고, 출수기 지상부건물중은 가벼워졌다. 2. 간장과 수장은 관개수 염분농도가 높을수록 짧아졌다. 3. 관개수 염분농도가 높을수록 수당 립수가 적어 ㎡당 립수가 적었으며, 등숙비율이 낮고 현미 천립중이 가벼워, 쌀 수량은 민물 관개(무처리)의 330㎏/10a에 비해 관개수 염분농도 0.1%는 94%, 0.3%는 85%, 0.5%는 76%, 0.7%는 71%의 수량을 얻었다. 4. 관개수 염분농도가 높을수록 완전립 비율은 낮아졌다. 따라서 간척지에서 중염도 토양(0.3~0.4%)에서 벼를 재배하여 유수형성기에 한발이 닥쳐 저류지 등 염분 농도 0.7%의 물로 5일간 담수하여도 쌀 수량은 29% 정도 감수되고 쌀의 품위도 저하되지만 어느 정도 수량은 얻을 수 있을 것으로 생각된다. This experiment was conducted at the Kyehwado Substation of the National Honam Agricultural Experiment Station(NHAES) RDA, Korea. The experimental field contained 0.38% NaCl in soil solution. The experiment was involved five treatments (control, 0.1, 0.3, 0.5, 0.7%) in a randomized complete block design with three replicates, saline solution was applied only one time at panicle formation stage for 5 days. Saegyehwabyeo, a japonica rice variety was used in this experiment. In yield components, Spikelets number per ㎡ decreased with increasing salinity level, particularly in the 0.7% of saline solution water. This factor affected the most yield reduction among the components. The percentage of ripened grain was inclined to decrease with increasing salinity level. 1,000 grain weight decreased with increasing salinity level but it was lest affected by salinity among yield components. The reduction of milled rice yield decreased significantly with increased saline water level, in detail 6% of yield reduction at the 0.1% saline solution, 15% at the 0.3%, 24% at the 0.5%, and 29% at the 0.7% saline solution level compared with control respectively. Results indicate that the gaining of rice yield could be reliable performance in terms of economical benefit for rice production even though high reduction of yield occurred at high salinity levels on a reclaimed saline soil in Korea.