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.

Sodium Trans-Bis(methyliminodiacetato)Chromate(Ⅲ)의 두가지 다른 空間群 P1￣와 A2/n間의 相互 變換

李珍昊,宋柱昊,崔成山,郭相姬,吳美蘭,박성진,李揆旺,徐廷善,徐日煥 충남대학교 1996 忠南科學硏究誌 Vol.23 No.1

The structure of sodium trans-bis(methyliminodiacetato) chromate(Ⅲ), C_10H_14O_8N_2CrNa, has been elucidated with two space groups P 1-; a=8.9856(6), b=13.308(1), c=6.261(1)Å, α=76.38(1), β=110.361(9), r=107.394(6)˚, V=662(2)Å^3, Z=2, μ=0.47mn^(-1), d=1.831Mg/㎥, R=0.0295 for 1901 independent reflections with F^2>2σ(F^2), and A2/n; a=13.65(5), b=6.261(1), c=16.85(6)Å, β=113.05(1)˚, V=1324(7)Å^3, Z=4, R=0.0287 for 1013 independent reflections with F^2>2σ(F^2). There are two different asymmetric half molecules in triclinic system and one asymmetric half molecule in monoclinic system. The structures of three different molecules are very similar in conformations. The four carboxyl O atoms and the two imino N atoms in each molecule produce a distorted octahedral coordination geometry around the Cr atom. The average distances of Cr-O(carboxyl) and Cr-N(imino) are 1.956 and 2.061Å respectively. Molecules are held together by ionic forces. In this paper, it has been also shown that the cell constants, Miller indices, atomic coordinates, lattice directions and reciprocal lattices of the two space groups can be mutually transformed.

자궁경부 편평상피병소에서 인체유두종바이러스 감염과 Ki-67표출에 대한 연구

김창진,강상균,이종칠 순천향의학연구소 1997 Journal of Soonchunhyang Medical Science Vol.3 No.2

The squamous cell carcinoma of the uterine cervix is the most common malignant tumor among women in Korea. Since 1976, when a research result that human papillomavirus(HPV) infection played some role in the tumorigenesis of the uterine cervical carcinoma had been published, numerous reports supporting the result has been released. They reported that about 90% of the carcinoma had some relation with HPV infections. About 20 subtypes of HPV has been observed in the anogenital lesions. As subtypes of the virus can be grouped into three according to the potentiality of malignant tumorigenesis, high risk group (HPV16, 18), intermediate risk group(HPV31, 33)and low risk group(HPV6/11), it is very important to identify the subgroups in the precancerous and cancerous lesions of the cervix for either diagnosis or prognosis. When HPV infects the epithelial cells, it promotes cellular proliferation. The cellular proliferation can be evaluated by immunohistochemistry with the antibodies for proliferting cell nuclear antigen(PCNA) and KI-67. Because PCNA has long half-life, and can be detected 48 hours after completion of mitosis, an estimation of proliferating cells by PCNA could be inaccurate. The expression of Ki-67 antigen is more correct than PCNA for the evaluation of proliferating cells due to its short half-life and rapid degradaton after completion of the mitosis. This study was conducted to see the relation between subtypes of HPV and cell proliferation by in situ hybridization(ISH) and immunohistochemistry in 60 cases of squamous intraepithelial lesions(SILs) and invasive carcinoma of the uterine cervix. The results are as follows; 1. HPV was detected in 50 out of 60 cases (83.5%). 2. The subtypes HPV6/11, the low risk group, were detected in 78.2% and 4.5% of low grade SIL and high grade SIL respectively, while not detected in any of invasive carcinomas. 3. The subtypes HPV 16, 18, the high risk groups, were detected in 4.3%, 59.1% and 80% of low grade SIL, high grade SIL and invasive carcinomas respectively. 4. In normal squamous epithelium and squamous metaplasia, the cell fraction expressing Ki-67 were 13.5%±6.7% and 8.7%±3.5%, while in low grade SIL, high grade SIL and invasive carcinomas they were 35.8±7.9%, 66.8±11.8% and 84±13.4% resepectively. 5. There was no relation between HPV subtypes and cell fractions expressing Ki-67. Above results shows that subtypes HPV6/11 are prevalent in low grade SILs, while HPV16, 18 are common in the high grade SIL and invasive carcinoma. It seems that there is no correlation between the cell fractions expressing Ki-67 and subtypes of HPV, which suggests that cellular proliferation can be induced by other than HPV infections. As the cell fraction expressing Ki-67 increases according to the grade of SIL and invasiveness, it would be useful prognostic factor along with the identification of high risk HPV type in the uterine cervical squamous epithelial lesions.

만성 요통환자의 복부 심부근과 표재근을 중심으로 한 운동 효과 비교

김진산,이창현,조미주,임연욱,정취산,김선엽 대한정형도수치료학회 2005 대한정형도수물리치료학회지 Vol.11 No.1

Objectives: To compare the efficacy of two types specific exercise intervention (deep and superficial abdominal muscle exercises) in the treatment of patients with chronic low back pain (CLBP). Design: A randomized, comparative, repeated-measures. Subjects: Twenty-four patients with CLBP (at least for 3 months), mean age±SD=51.58±16.21 (yrs). Methods: Twenty-four patients with this condition were assigned randomly to two treatment groups. Both first and second group underwent 3 weeks specific exercise treatment program. The first group specific trained for the deep abdominal muscles. The second group specific trained for the superficial abdominal muscles. Results: After intervention, the first group showed a statistically significant reduction in pain intensity and functional disability levels (p<.05). The second group showed no significant change in these parameters after intervention (p>.05). Conclusions: According to results, a "deep abdominal muscle exercises" treatment approach appears more effective than a "superficial abdominal muscle exercises" treatment in patients with CLBP.

회전자 구조에 따른 SRM의 토오크 특성해석

정도영,이상호,서진우,오홍석,최경호 三陟大學校 1997 論文集 Vol.30 No.1

The switched reluctance motor(SRM) has a simple rotor construction with no windings. It also has simple concentrated windings on the stator. Thus, it is expected to be a lower cost machine to manufacture than the squirrel cage induction motor. This paper presents an advanced rotor structure type, well-round rotor type in SRM. To design the improved SRM we have used FEM and studied and compared with each other. The static torque, instantaneous torque and average torque are more improved than that of typical rotor type which has been a lot of used for SRM.

原點選擇에 따른 構造因子의 位相變化 : Triclinic, Monoclinic, Orthorhombic System에서 Primitive이면서 Centrosymmetric인 Space Groups에만 適用 Only for Primitive and Centrosymmetric Space Groups of Triclinic, Monoclinic and Orthorhombic Systems

徐日煥,李珍昊,郭相姬,崔成山 충남대학교 기초과학연구소 1995 忠南科學硏究誌 Vol.22 No.2

Triclinic, monoclinic, orthorhombic systems에서 primitive이면서 centrosymmetric space group이면 8가지 對稱中心點中 任意의 한 點을 原點으로 指定하기 爲하여 3個의 structure factor에게 任意의 phase를 割當할 수 있음을 보였다. 이들 phase들은 direct method에서 structure factor의 phase를 決定해가는 basic set이 될 수 있다. In any primitive and centrosymmetric space group in the triclinic, monoclinic, or orthorhombic systems, arbitrary signs can be allocated to three reflections in order to specify the origin at one of the eight centers of symmetry. These signs form a basic set, from which more and more signed reflections emerge in the process of direct method.

한국 재래산양에서 Bovine Viral Diarrhea, Bovine Herpesvirus-1, Parainfluenza Type-3 바이러스에 대한 혈청학적 연구

한동운,권용국,문진산,윤소라,위성환,장환,탁동섭,이태욱,강문일 한국수의공중보건학회 2003 예방수의학회지 Vol.27 No.3

The 948 goat sera were serologically tested for ten pathogens including bovine viral diarrhea (BVD), bovine herpes virus type-1 (BHV-1) and parainfluenza virus type-3 (PI-3). By viral neutralizaion test, three pathogens including BVD virus, BHV-1, PI-3 were applied for screening each neutralizing antibody and its titration. Among 948 sera, there were 215 seropositives (22.7%) against BVD virus, 25 (2.6%) against BHV-1 virus, and 161 (17.0%) against PI-3 virus, respectively. In the seropositive cases to BVD virus, provincial prevalence of them were recorded as Gyeongnam(30.8%) for the highest one, while as Jeonbuk (15.8%) and Gyeongbuk(l6.7%) relatively for the lower ones. Among them, higher than 1:8 in antibody titration was classified as 74 cases (34.4%) which were suspected the cycle of its infection in their herds. Among the seropositives to BHV-1, it was relatively lower prevalence rate ranging from 1.7% to 6.7% that those of BVD virus and PI-3, but more importantly they were prevailing across the country. Most of the seropositive cases (42.9%) to PI-3 were classified as 1:4-1:16 in titration, but also distributed all around the country. The prevalence in goats varied according to areas (15.8 to 30.8%). Related to the provincial prevalence of three viral agents in Korean goats, it seemed that three viral pathogens would be directly or indirectly involving in various disorders as primary or secondary causative agents resulting in decreased productivity.

우수방사성의약품 생산시설 개발

신병철,정원명,박상현,이규일,박경배,박진호 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.2

Manufacturing facilities of the pharmaceuticals must meet certain level of the cleanness required so that foreign substances such as dust, moisture, heat, microorganism, or virus do not contaminate the product. In case of radiopharmaceuticals for medical treatment and diagnosis, not only should the operators and environment be protected from radiation but also need to be isolated from the foreign contaminant. Therefore, manufacturing facilities for radiopharmaceuticals must satisfy the design standards of both hot cell and clean room which are specified by GNP. However, standards of maintaining negative pressure for preventing spread of radioactive contaminant in isolated facilities conflict with the standards of maintaining positive pressure for keeping cleanness. To solve this problem, are pressure of hot cell was designed lower than in the adjacent area to meet standards of the radiation safety. To keep higher cleanness in certain part of the hot cell for filling, minimal relative positive pressure allows. In order to effectively maintain the cleanness that is required for production of Tc-99m generator, which takes 70% of whole demand of radiopharmaceuticals, the rooms placed in each side of production room are used as a buffer area and three lead hot cells are installed in production room. In this research, we established the appropriate engineered design concept for Tc-99m generator manufacturing facility, which satisfies both GMP cleanness standard for preventing particles, bacteria, other contaminants and the regulations of radiation safety for supervising and controlling the amount of radiation exposure and exhausted radioactivity. And the concept of multi-buffer zones is introduced to apply negative air pressure for hot cell with first priority and to continue relative positive air pressure for clean room.

한국 재래 산양에서 Leptospira spp.에 대한 혈청역학적 연구

한동운,권용국,문진산,윤소라,위성환,장환,탁동섭,이태욱,강문일 한국수의공중보건학회 2003 예방수의학회지 Vol.27 No.3

Between January 1999 and September 2001, 948 sera (120 from each province except 108 from Chungbuk) from 8 provinces were sampled from Korean goats. All the samples were serologically tested for Leptospira spp. By the microscopic agglutination test against four L. interrogans serovars including canicola, icterohaemorrhagiae, pomona and hardjo, 948 Korean goats were confirmed as 11 seropositives (1.2%) only infected with L. icterohemorrhagiae. All positive sera were collected from Gyeonggi (5), Gangwon (4) and Chungbuk (2). Titration of them were classified as 1:100 of 10 sera except one case with 1:200 from Gyeonggi. It was meaningful that the pathogen in Korean goats was mainly distributed in the northen part of the country. Consequently, the results in the study were confirmed and analyzed the recent status of infection of leptospirosisas zoonotic agentsome in Korean goats.

Phase I trial and pharmacokinetic study of tanibirumab, a fully human monoclonal antibody to vascular endothelial growth factor receptor 2, in patients with refractory solid tumors

Lee, Su Jin,Lee, Seon Young,Lee, Weon Sup,Yoo, Jin San,Sun, Jong-Mu,Lee, Jeeyun,Park, Se Hoon,Park, Joon Oh,Ahn, Myung-Ju,Lim, Ho Yeong,Kang, Won Ki,Park, Young Suk Springer US 2017 Investigational new drugs Vol.35 No.6

<P><B>Summary</B></P><P><I>Background</I> Tanibirumab is a fully human monoclonal antibody to vascular endothelial growth factor receptor 2 (VEGFR-2). We conducted a first-in-human phase I study of tanibirumab in patients with solid tumors refractory to standard chemotherapy. Primary endpoints were evaluating safety, pharmacokinetics (PKs), estimating maximum-tolerated dose (MTD) and recommended phase II dose (RP2D). <I>Methods</I> We designed our study to escalate tanibirumab at 9 different dose levels with a 3 + 3 method and tanibirumab (1–28 mg/kg) was administered intravenously on D1, 8, 15 in 28-day courses. Dose limiting toxicities (DLTs) were only assessed during the first cycle of treatment and response evaluation was performed every 2 cycles. The effects of tanibirumab on several angiogenic factors were analyzed. <I>Results</I> From October 2011 to September 2013, a total of 26 patients with refractory solid tumors were enrolled. The median age was 58 years (range, 27–75) and 20 patients were male. The most common tumor type was colorectal cancer (<I>N</I> = 19) and seven patients had a history of previous bevacizumab treatment. As hemangioma continued to occur, the final dose level, 28 mg/kg, was not performed. DLTs were not found, and the MTD was confirmed to be 24 mg/kg. Hemangioma was observed in 16 patients (61.5%), but all were grade 1–2 and disappeared after discontinuation of the study drug. Among the 18 patients in the efficacy set, no objective response was observed, but 11 patients showed stable disease. PKs were characterized by dose-dependent linear exposure and the mean trough concentrations exceeded biologically relevant target levels at 12 mg/kg and above. Serum VEGF, soluble VEGFR-2, and PlGF increased at the 4 mg/kg dose level and above. <I>Conclusions</I> Treatment with tanibirumab showed a tolerable toxicity profile and modest clinical efficacy in patients with refractory solid tumors. A phase II trial of tanibirumab is ongoing now.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s10637-017-0463-y) contains supplementary material, which is available to authorized users.</P>