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.

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results: In 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

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).

사립체 DNA 뉴클레오타이드 3243 A→G 돌연변이 [MTTL1^*MELAS3243G]에 의한 MELAS 증후군

박기형,김승현,이영주,김희태,김주한,김명호,박성섭 대한신경과학회 1998 대한신경과학회지 Vol.16 No.4

Brucella abortus 국내 분리주의 36kDa 외막단백을 암호하는 omp2b 유전자의 염기 분석

허지연,김지영,송근호,김명철,박창식,김태용,김정화,전무형 충남대학교 형질전환복제돼지연구센터 2004 논문집 Vol. No.8

B. abortus 국내 분리주의 분자유전학적 성상을 규명하고 분자역학적 연구에 필요한 기초자료를 얻기 위해 36kDa OMP를 암호하는 omp2b 유전자를 PCR법으로 확인하고,그리고 omp2b 유전자의 핵염기 서열과 아미노산 서열을 결정하고 이 결과를 Brucella 표준균주 및 여러 동물에서 분리된 Brucella 분리주와 상호 비교 분석하였던 바 다음과 같은 결과를 얻었다. 1. B. abortus 분리 주 (7주)에 대해 omp2b primers를 이용하여 PCR을 수행한 바 공시한 참조균주와 분 리균주 모두에서 1,251bp의 특이한 DNA 절편이 각각 증폭되었다. 2. omp2b 유전자의 1,089bp에 대한 염기서열과 이에 대한 362개의 아미노산 서열을 결정하였다. 분리 균주의 omp2b 유전자의 염기서열을 참조균주와 비교 분석한 결과 B. abortus 2308 (biovar 1) 및 B abortus B3196 (biovar 5)과는 99.6%∼100% 및 99.5%∼99.9%의 매우 높은 상동성을 나타내었고,B. abortus 45/20 (biovar 1)과는 97.1%~97.4%의 상동성을 나타내었다. 또한 362개의 아미노산 서열에 대해 분석하였던 바,분리균주들은 B.abortustus 2308 (biovar 1) 및 B. abortus B3196 (biovar 5)과는 99.2%∼100%의 매우 높은 상동성을 보였으며,B. abortus 45/20 (biovar 1)과는 96.4%∼ 97.2%의 상동성을 보였다. 3. 본 시험에 공사된 브루셈라균주의 omp2b 유전자 서열과 여러 동물에서 분리된 브루셀라 분리주의 자료를 바탕으로 phylogenetic tree를 작성 한 바,국내 분리주는 B. abortus 2308 (biovar 1),B. abortus B3196 (biovar 5),B. abortus 45/20 (biovar 1),B. suis 1330 (biovar 1),B. melitensis 16M (biovar 1),B. canis NCTC 01854,B. neotomae 5K33과 97.3% 이상의 높은 근연성을 보이며 동일한 cluster에 소속되었으며,omp2b 유전자는 매우 잘 보존됨을 알 수 있었다. omp2b gene of Brucella abortus isolates encoding 36kDa outer membrane protein (OMP) was amplified by polymerase chain reaction (PCR) and the sequences of nucleotide and amino acid were determined and analyzed to obtain the basic data for molecular epidemiological features of brucellosis in Korea. In PCR using omp2b primers for the gene of 36kDa aMP, the specific signals at 1,251bp were demonstrated, The nucleotide sequences of omp2b gene of 1,089bp were sequenced by dye terminator cycle sequencing method, and 362 amino acid sequences were predicted. As compared the nucleotide sequences with those of B. abortus reference strains, the isolates showed the very high homology to the reference strains ranging 97.1%∼100%. The similar results were also obtained in the analysis of the amino acid sequences. In the phylogenetic tree, the isolates clustered with the reference strains and the majority of strains originated from pig, dog, wood rat and cattle.

Brucella abortus 국내 분리주의 36kDa 외막단백을 암호하는 omp2b 유전자의 염기 분석

허지연,김지영,송근호,김명철,박창식,김태용,김정화,전무형 한국수의공중보건학회 2003 예방수의학회지 Vol.27 No.1

B. abortus 국내 분리주의 분자유전학적 성상을 규명하고 분자역학적 연구에 필요한 기초자료를 얻기위해 36kDa OMP를 암호하는 omp2b 유전자를 PCR법으로 확인하고, 그리고 omp2b 유전자의 핵염기 서열과 아미노산 서열을 결정하고 이 결과를 Brucella 표준균주 및 여러 동물에서 분리된 Brucella 분리주와 상호 비교 분석하였던 바 다음과 같은 결과를 얻었다 1. B. abortus 분리주 (7주)에 대해 omp2b primers를 이용하여 PCR을 수행 한 바 공시한 참조균주와 분리균주 모두에서 1,251bp의 특이한 DNA 절편이 각각 증폭되었다 2. omp2b 유전자의 1,089bp에 대한 염기서열과 이에 대한 362개의 아미노산 서열을 결정하였다. 분리균주의 omp2b 유전자의 염기서열을 참조균주와 비교 분석한 결과 B. abortus 2308 (biovar 1) 및 B. abortus B3196 (biovar 5)과는 99.6%~l00% 및99.5%~99.9%의 매우 높은 상품성을 나타내었고, B. abortus 45/20 (biovar 1)과는 97.1%~97.4%의 상품성을 나타내었다. 또한 362개의 아미노산 서열에 대해 분석하였던 바, 분리균주들은 B. abortustus 2308 (biovar 1) 및 B. abortus B3196 (biovar 5)과는 99.2%~l00%의 매우 높은 상품성을 보였으며, B. abortus 45/20 (biovar 1)과는 96.4%~97.2%의 상품성을 보였다. 3. 본 시험에 공시된 브루셀라균주의 omp2b 유전자서열과 여러 동물에서 분리된 브루셀라 분리주의자료를 바탕으로 phylogenetic tree를 작성 한 바, 국내 분리주는 B. abortus 2308 (biovar 1), B. abortus B3196 (blovar 5), B. abortus 45/20 (biovar 1), B. suis 1330 (biovar 1), B. melitensis 16M (biovar 1), B. canis NCTC 01854, B. neotomae 5k33과 97.3%이상의 높은 근연성을 보이며 동일한 cluster에 소속되었으며, omp2b 유전자는 매우 잘 보존됨을 알 수 있었다. omp2b gene of Brucella abortus isolates encoding 36kDa outer membrane protein (OW) was amplified by polymerase chain reaction (PCR) and the sequences of nucleotide and amino acid were determined and analyzed to obtain the basic data for molecular epidemiological features of brucellosis in Korea. In PCR using omp2b primers for the gene of 36kDa OMP, the specific signals at 1,251bp were demonstrated, The nucleotide sequences of omp2b gene of 1,089bp were sequenced by dye terminator cycle sequencing method, and 362 amino acid sequences were predicted. As compared the nucleotide sequences with those of B. abortus reference strains, the isolates showed the very high homology to the reference strains ranging 97.1%-100%. The similar results were also obtained in the analysis of the amino acid sequences. In the phylogenetic tree, the isolates clustered with the reference strains and the majority of strains originated from pig, dog, wood rat and cattle.

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

들깨풀 첨가가 열무 물김치의 발효에 미치는 영향

김형렬,박정은,장명숙 한국조리과학회 2002 한국식품조리과학회지 Vol.18 No.3

An optional ingredient Perilla Seed paste was adopted to improve the quality of Yulmoo Mul-kimchi during fermentation. The final weight percentage of perilla seed paste in Yulmoo Mul-kimchi was adjusted to 0, 10, 20, 30, and 40% per water respectively. Chemical and sensory characteristics were determined during fermentation at 10℃ for 25 days. The effect was varied depending on the amounts of perilla seed paste, but Yulmoo Mul-kimchi fermented with 20% perilla seed paste was most favored for color, smell, sour taste, carbonated taste, texture and overall acceptability in the sensory evaluation. The pH decreased with the increase of total acidity. The total vitamin C content increased initially to the certain level at a certain time of fermentation depending on the level of perilla seed paste, and then decreased later. In case of reducing sugar, the 20% treatment showed the highest content. Turbidity values were generally increased in all samples during fermentation, even though the extents were limited. Total plate count and the number of lactic acid bacteria were gradually increased and then decreased showing the maximum microbial counts during fermentation. The optimum levels of perilla seed paste in Yulmoo Mul-kimchi obtained through experiments were between 20 and 30% of added water content, preferably 20% for color, fermentation-retarding effect, and sensory taste of the product.

임신 중 고혈압성 질환에 대한 임상적 고찰

김경철,정명철,김호성,조민형,고재환,김용봉 白中央醫療院 2005 仁濟醫學 Vol.26 No.1

Objective: The aim of this study was to investigate the clinical charact eristics of pregnancy induced hypertension(PIH). Methods: We retrospectively evaluated the clinical characteristics through the collected data of 176 PIH cases treated at Seoul Paik hospital from March 1995 to December 2002. Results: The proportions of severe PIH, mild PIH, and chronic hypertension were 70%, 24%, and 6% of the cases, respectively. According to maternal age, the highest rate of 45% was noted in the group of 26-30 years of age. The rate of cesarean(80%) was higher than the rate of vaginal delivery(20%). The blood pressure was controlled by hydralazine for 70% of the patients. The rate of single gestation was 90%. The birthweight of 20% of the newborn were 2500gm or more. The anemia, twin pregnancy, postpartum hemorrhage, pulmonary edema, and infection were found in 30%, 10%, 3%, 2%, and 1% of the PIH patients, respectively. In respect of the perinatal complications, the rates of low birth weight, stillbirth, and neonatal death were 80%, 3%, and 1%, respectively. Conclusion: We were able to decrease the mortality and morbidity of PIH patients and neonates with strict antenatal care and proper treatment.

대동물 임상에서의 침술마취의 적용

김명철,김덕환,전무형,홍성혁,박창식,이재일,이수진,김영석 충남대학교 형질전환복제돼지연구센터 2004 논문집 Vol. No.8

Acupuncture is used to treat pathological conditions and to prevent pain from arising. The pathological conditions that can be treated can be painless or painful conditions. Acupuncture analgesia (AA) is a specific form of acupuncture; the stimulation of the acupuncture points must be strong and long (about 15 to 30 minutes) before a local or general analgesia or hypalgesia will develop. Development of modern AA began in the late fifties. Effectiveness of acupuncture in alleviation of pain was quickly noticed and brought to the medical researchers and surgeons. Through their diligent pursuit, AA has been established as a viable alternative for relief of pain and substitution of conventional anesthesia. In veterinary medicine. early successful applications of AA to surgery of domestic animals were reported in the late sixties. Local or regional anesthesia is often preferred to general anesthesia in cattle. Acupuncture was effective in inducing analgesia. Regional electroacupuncture analgesia is potentially useful for standing surgeries in cattle. Some standing surgeries may be easily accomplished using electroacupuncture anesthesia.