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.

목형의 엔드 밀링시 절삭조건에 따른 가공 특성에 관한 연구

김성일,김종택,김민호,신형곤,김태영 한국공작기계학회 2006 한국공작기계학회 추계학술대회논문집 Vol.2006 No.-

The cutting tests of wood patterns are carried out using CNC milling machine. The cutting forces and surface characteristics of machined surface are investigated at various cutting conditions such as spindle speed, feed speed, cutting direction of wood pattern and wood material. In the CNC end-milling, the surface roughness increases as feed speed increases and decreases as spindle speed increases. However, the cutting force and surface roughness are different along the cutting direction and material of wood pattern.

CD34+ 조혈 모세포 이식 2례

김정아,정현식,김원석,윤성수,이홍기,박찬형,박성규,김동욱,이종욱,한치화,민우성,김춘추,김동집 대한조혈모세포이식학회 1996 대한조혈모세포이식학회지 Vol.1 No.1

Background: In most solid tumors, the CD34 antigen has not been detected, so positive selection of CD34+ cells may reduce tumor cell contamination and the CD34+ cells are capable of reconstituting hematopoiesis. We tried CD34+ cell transplantation in two patients. Method: CD34+ cells from chemotherapy + G-CSF mobilized PBPCs or bone marrow were positively selected with an avidin-biotin immunoadsorption column (CEPRATE SC system). Case 1. One course of chemotherapy using cyclophosphamide(200㎎/㎡) and etoposide (4.2g/㎡), combined with G-CSF(5㎍/㎏) S.C. was used in a relapsed lymphoma patient. This patient responded to the induction chemotherapy. CD34+ cells from harvested bone marrow were selected by the CellPro immunoadsorption column. The total number of mononuclear cells loaded onto the CellPro was 2.4×10^(8)/㎏, with 1.1% CD34+ cells. After column separation, the total number of positively selected cells was 5.16×10^(6)/㎏. The number of CFU-GM was 76.8×10⁴/㎏. This patient was treated with melphalan (140㎎/㎡) and TBI (1200cGy) and the positively selected CD34+ cells were infused. The time to neutrophil recovery greater than 0.5×10^(9)/L was 19 days and the time to platelet recovery greater than 50×10^(9)/L was 21 days. Case 2. Two courses of mobilizing chemotherapy were given 4 weeks apart using taxol(210㎎/m2) and adriamycin(60㎎/m2), combined with G-CSF(5㎍/㎏) S.C. in a breast cancer patients with 7 axillary node metastasis. CD34+ cells from each single leukapheresis product were selected by the CellPro immunoadsorption column. In the first collection, the total number of nucleated cells was 4.4×10^(8)/kg, with 0.42% CD34+ cells. In the second collection, the total number of nucleated cell was 2.8× 10^(8)/㎏ with 0.43% CD34+ cells. After colum separation, the total numbers of collected cells were 4.0×106/kg and 4.8×10^(6)/kg, the total number of CD34+ cells were 1.2×10^(6)/㎏ and 0.82×10^(6)/㎏. Colonogenic assays of positively selected CD34+ cells gave rise to myeloid erythroid, and multilineage colonies, with a median of 190 CFU-GM, 190 BFU-E, and 164 CFU-GEMM per 1×10³ adsorbed cells, respectively. High-dose chemotherapy with cumulative doses of 40mg/㎡ mitoxantrone, 750mg/㎡ thioptepa, and 1000mg/㎡ carboplatin was administered. Positively selected CD34+ cells were rapidly infused 24 hours after the end of high-dose chemotherapy. The time to neutrophil recovery greater than 0.5×10^(9)/L was 16 days and the time to platelet recovery greater than 50×10^(9)/L was 20 days.

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.

하악골에 발생한 골막 골육종

김태우,김승범,권혁찬,문선재,윤정훈,김형준,차인호,육종인,김진 대한악안면성형재건외과학회 2002 Maxillofacial Plastic Reconstructive Surgery Vol.24 No.1

Periosteal osteosarcoma is a distinct entity of malignant bone tumor with characteristic clinical, morphological, and histological features within the group of juxtacortical osteosarcoma. Periosteal osteosarcoma is predominantly located in the tubular long bones, and extremely rarely involving the jaws. A case of periosteal osteosarcoma of the right mandible is presented. A 27-year-old woman complained of the gingival swelling and bleeding tendency of the right posterior mandible. Clinical examination revealed a reddish brown strawberry-like swelling on the affected mucosa, which measured 1.5㎝×1.5㎝. The tumor was located on the lingual cortex of the mandible and extended into the surrounding soft tissues. Microscopically, the tumor consisted exclusively of atypical chondroblastic cells with a small osteoblastic area. A minimal bone marrow involvement was noted and the adjacent cortex was free of tumor. These findings suggested that the tumor originated from the periosteal cambium layer, which lies between the periosteal fibrous layer and the cortex of mandible.

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).

Curcumin ameliorates cadmium-induced nephrotoxicity in Sprague-Dawley rats

Kim, Kyeong Seok,Lim, Hyun-Jung,Lim, Jong Seung,Son, Ji Yeon,Lee, Jaewon,Lee, Byung Mu,Chang, Seung-Cheol,Kim, Hyung Sik Elsevier 2018 Food and chemical toxicology Vol.114 No.-

<P><B>Abstract</B></P> <P>Chronic exposure to cadmium (Cd) causes remarkable damage to the kidneys, a target organ of accumulated Cd after oral administration. The aim of the present study was to investigate the protective effect of curcumin against Cd-induced nephrotoxicity. Sprague–Dawley male rats were divided into the following four treatment groups: control, curcumin (50 mg/kg, oral), CdCl<SUB>2</SUB>, (25 mg/kg, oral), and pre-treatment with curcumin (50 mg/kg) 1 h prior to the administration of CdCl<SUB>2</SUB> (25 mg/kg, oral) for 7 days. At 24 h after the final treatment, the animals were killed, and the biomarkers associated with nephrotoxicity were measured. Our data indicated that blood urea nitrogen (BUN) and serum creatinine (sCr) levels were significantly reduced by curcumin pre-treatment in CdCl<SUB>2</SUB>-treated animals. Histopathological studies showed hydropic swelling and hypertrophy of the proximal tubular cells in the renal cortex after Cd treatment. Pretreatment with curcumin ameliorated the histological alterations induced by Cd. The urinary excretion of kidney injury molecule-1 (Kim-1), osteopontin (OPN), tissue inhibitor of metalloproteinases 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL), and netrin-1 significantly reduced by curcumin treatment compared to that in the CdCl<SUB>2</SUB>-treated group. The administration of curcumin provided a significant protective effect against Cd-induced nephrotoxicity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Curcumin protects against cadmium-induced renal injury. </LI> <LI> Curcumin reduces urinary excretion of AKI biomarkers. </LI> <LI> Curcumin protects against cadmium-induced apoptosis in the kidney. </LI> </UL> </P>

간 세포암에서 VEGF, TGF-β1, b-FGF 발현의 의의

김성용,남충현,주종우,채만규,백무준,이문수,김형철,안현철,김홍수,김창진,김창호 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1

Purpose: Angiogenesis is important for the proliferation and the metastasis of solid tumors. The growth of a solid tumor is widely recognized to depend on the process of neovascularrozation. Without angiogenesis, tumors cease to grow beyond even a few milimeters in diameter. It has been shown that tumor vascular density is an independent prognostic marker in several types of human tumors and is known to correlate with poor prognosis. To date, many angiogenic factors have been identified, such as transforming growth factor-α(TGF-α), transforming growth factor-β(TGF-β), fibroblast growth factor family(FGF), vascular endothelial growth factor(VEGF), platelet derived endothelial cell growth factor(PD-ECGF), tumor necrosis factor-α(TNF-α), and angiogenin. Hepatocellular carcinoma(HCC) is the second most common tumor in Korean males and is known as a typical hypervascular tumor with frequent portal vein invastion. The authors identified the expreesion of VEGF, TGF-β1, and b-FGF in HCC specimens and evaluated the relationship between these growth factors and the clinicopathologic characteristics of HCC. Method: We reviewed the medical records of 30 patients who were diagnosed as hepatocellular carinoma treated with hepatic resection between January 1994 and December 1998 in Soonchunhyang University Chunan Hospital. The selection of the cases was decided according to the condition of paraffin block fixation. The prognostic factors such as age, sex, tumor size, concentration of serum α-fetoprotein, presence of liver cirrhosis, presence of tumor emboli in portal vein, TMN stage, amount of transfusion during the operation, hepatitis B virus(HBV) infection, and Edmonson-Steiner(E-S) grade were investigated. Relationship between the prognostic factors and the immunopathologic expression of the TGF-β1, b-FGF, and VEGF was examined. Result: Thirty patients (24 males, 6 females) were included in the current study. The patient's mean age was 50.6 years and the age ranged from 36 to 65 years. The mean size of the tumor was found to be 5.2cm. All the patients were follewed up for 7 to 63 months. Child's classification A patients were 23(76.7%)cases, B patients were 7(23.3%)cases, and C was none. Immunohistochemical staining of HCC tumor mass in VEGF expression patients were 17(56.7%), b-FGF expression patients were 10(33.3%), and TGF-β1 expression patients were 10(33.3%). VEGF expression or more than one positive expression among the three factors correlated with tumor size and the stage of HCC but did not correlated with other clinicopathological characteristics. TGF-β1 and b-FGF did not correlate with any clinicopathological characteristics. Conclusion: The results suggest that the expression of VEGF or more than one positive expression among the three factors in HCC cells may be a significant prognostic factor of HCC.

장기간의 에어로빅스 운동이 골형성 및 각종 호르몬과의 상관관계

김종인,김은희,김주혁,김수진,김도형,장성동 한국스포츠리서치 2004 한국 스포츠 리서치 Vol.15 No.3

Selected girl mid㎗e school of 14- and 15- years-old who got 35% body fat rate and are obese, and have them aerobics exercise for 20 weeks, the conclusion on the matter of change between Osteoporosis and Hormones showed. The contents of Calcium has significant difference(p<.05) between 9.38±0.34㎎/㎗ pre-exercise and 9.34±0.29㎎/㎗ post-exercise, and the contents of Glucose has significant difference (p<.05) between 78.0±5.38㎎/㎗ pre-exercise and 81.3±5.91㎎/㎗ post-exercise. parathyroid hormone (PTH) is shown as 11.2±3.06pg/㎖ at pre-exercise arid 13.8± 4.41pg/㎖ at post-exercise, hyperparathyroidism and osteoporosis (Osteocalcin) is shown as 6.04±3.56ng/㎖ at pre-exercise and 5.29±4.92ng/㎖ at post exercise, there is no significant difference. Deoxypyridinoline is shown as like 8.18±2.43nM/mMcre pre-exercise arid 9.97±2.76nM/mMcre post-exercise, Alkaline phosphatase (ALP), which has an effect on the born disease, is shown 229.7±61.66[U/㎖ pre-exercise and 224.3±8.27 [U/㎖ post-exercise, there is significant difference(p<.0l). There is significant difference (p<.05) between Growth Hormone and Parathyroid hormone(PTH) which is bone absorption hormone, the Osteocalcin which is the mark of born-formation, there is no significant difference among the index of born formation mark, lipid, and hormones.

대황황련해독탕의 항고지혈증 작용

김영석,정은아,장종철,양형길,김남재,조기호,배형섭,이경섭,김동현 경희대학교 동서의학연구소 2001 東西醫學硏究所 論文集 Vol.2001 No.-

Whangryunhaedok-Tang (WT) is formulated with Coptidis Rhizoma, Phellodendri Cortex, Scutellariae Radix and Gardeniae Fructus, and Daewhang-whangryunhaedok-Tang (DWT) is made by the combination of Rhei Rhizoma, a wellknown anticostipation drug in WT. Therefore, DWT has been evaluated for antihyperlipidemic effects on experimental hyperlipidemic rats and mice induced by corn oil and high cholesterol-diet. Oral administration of DWT significantly inhibited the increase of serum triglyceride and LDL-cholesterol levels, and the decrease of serum HDL-cholesterol levels in hyperlipidemic rats induced by corn oil. Also, oral administration of DWT significantly prevented the increase of serum total cholesterol, triglyceride and LDL-cholesterol, and liver total cholesterol and triglyceride in 1% cholesterol-diet fed mice. These results suggest that DWT is effective for the treatment of hyperlipidemia.