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Yoon, Se-Hee,Cho, Jang-Hee,Kwon, Owen,Choi, Ji-Young,Park, Sun-Hee,Kim, Yong-Lim,Yoon, Young-Ran,Won, Dong-Il,Kim, Chan-Duck Lippincott Williams Wilkins, Inc. 2013 Transplantation Vol.95 No.6
BACKGROUND: We prospectively studied renal transplant recipients receiving tacrolimus to determine the relationship between the CYP3A4, CYP3A5, and ABCB1 genetic polymorphisms and the pharmacokinetics (PK) and pharmacodynamics (PD) of tacrolimus and its metabolites. METHODS: Renal transplant recipients receiving tacrolimus were genotyped for CYP3A4*4, CYP3A4*5, CYP3A4*18, CYP3A5*3, ABCB1 c.1236C→T, ABCB1 c.2677G→A/T, and ABCB1 c.3435C→T. Dose-adjusted trough concentration (C0) of tacrolimus and its metabolites (M-I and M-III) and PK and PD (T-cell and monocyte subsets) were determined on transplantation days –2, 5, 30, and 90 and correlated with the corresponding genotypes. RESULTS: The dose-adjusted C0 of tacrolimus and its metabolites and AUC0–12 were significantly higher and the mean fluorescence intensity (MFI) of HLA/DR in monocytes was significantly lower in patients with CYP3A5*3/*3 than in patients with CYP3A5*1/*1 or CYP3A5*1/*3. However, there was no significant difference in the dose-adjusted C0 of tacrolimus and its metabolites, PK and PD among the ABCB1 genotypes. The MFI of HLA/DR in monocytes showed a significant negative correlation with dose-adjusted C0 of tacrolimus and its metabolites and AUC0–12. In a multiple regression analysis, the presence of the CYP3A5*3/*3 genotype was a significant independent variable determining the dose-adjusted C0 of tacrolimus and its metabolites, AUC0–12, and the MFI of HLA/DR in monocytes. CONCLUSIONS: This study demonstrates that the CYP3A5 genetic polymorphisms are associated with the individual differences in PK and PD as well as in C0 of tacrolimus and its metabolites. The MFI of HLA/DR in monocytes might be considered to be a significant tool for monitoring tacrolimus efficacy.
( Hee Yeon Kim ),( Jong Young Choi ),( Chung Hwa Park ),( Do Seon Song ),( Myeong Jun Song ),( Jeong Won Jang ),( Jung Hyun Kwon ),( Chan Ran You ),( Si Hyun Bae ),( Seung Kew Yoon ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1
Background: Several studies demonstrated that preemptive antiviral therapy reduced hepatitis due to hepatitis B virus (HBV) reactivation and hepatic morbidity during transarterial chemo-lipiodolization (TACL) in HBV-related hepatocellular carcinoma (HCC) patients. However, the efficacy of antiviral therapy on survival in patients with HBV-related HCC is still unclear. The aim of this study is to evaluate the long-term outcome of antiviral therapy in HBV-related HCC undergoing TACL. Methods: From January 2003 to May 2007, 177 newly diagnosed HBV-related HCC patients underwent TACL were retrospectively enrolled in the study. Among these, 66 patients received preemptive lamivudine therapy during TACL while others had not taken antiviral therapy until viral reactivation. Results: During the median follow-up of 11.1 months, 57 (50.3%) patients developed HBV reactivation in the control group and 14 (24.3%) patients developed viral breakthrough in the lamivudine group. Hepatitis attributed to HBV reactivation or viral breakthrough was occurred in 35 (30.9%) patients among the control group and in 10 (15.2%) patients among the lamivudine gtroup. Multivariate analysis identified age >50 years (p=0.002), reactivation or viral breakthrough (p=0.036) and UICC stage IV (p<0.001) to be independent predictors of overall survival. In the stratified analysis according to the UICC stage, preemptive lamivudine therapy did not influence on the overall survival. Conclusions: Preemptive lamivudine therapy can reduce the HBV reactivation in HBsAg-positive HCC patients receiving TACL. However, preemptive lamivudine therapy also raised concerns about viral breakthrough due to HBV mutation. Preemptive lamivudine therapy did not showed long term efficacy on the survival.
Prevalence of Salmonella Isolates and Antimicrobial Resistance in Poultry Meat from South Korea
YOON, RAN-HEE,CHA, SE-YEOUN,WEI, BAI,ROH, JAE-HEE,SEO, HYE-SUK,OH, JAE-YOUNG,JANG, HYUNG-KWAN International Association for Food Protection 2014 Journal of food protection Vol.77 No.9
<P>Contamination of Salmonella was assessed in duck and chicken meat collected from supermarkets, traditional markets, internet shopping malls, and wholesale markets in Jeonlado, South Korea, in 2013. Salmonella contamination was found in 51.3% of duck meat samples and 3.7% of chicken meat samples. Salmonella contamination of duck meat samples differed by meat type, i.e., 69.8% of samples of whole ducks and 33.9% of samples of duck pieces. Six serotypes were identified from 64 Salmonella isolates in duck meat: Salmonella Typhimurium (37.5%), Salmonella Enteritidis (21.8%), Salmonella Stanley (3.1%), Salmonella Regent (1.6%), Salmonella Winterthur (3.1%), and Salmonella Westhampton (1.6%). All isolates were resistant to one or more antibiotics. Resistance to sulfisoxazole was most common (93.8% of isolates), followed by resistance to nalidixic acid (59.4%), ceftazidime (26.6%), and ampicillin (26.6%). To our knowledge, this study is the first to report Salmonella contamination in duck meat from Korea. Duck meat should be considered an important source of foodborne pathogens.</P>
( Hee Geun Park ),( Deog Jo Jung ),( Jun Hyun Jeong ),( Jong Kui Jun ),( A Ram Yoon ),( Young Ran Lee ),( Kyung Eun Min ),( Myung Hwa Kim ),( Kwang Moo Lee ),( Wang Lok Lee ) 한국운동영양학회 2013 Physical Activity and Nutrition (Phys Act Nutr) Vol.17 No.1
This study investigated the effect of aerobic exercise training on immune cell proliferation and inflammatory cytokine production in the spleen of high fat diet-induced obese mice. C57B1J6 male mice (4 weeks aged. n20) were fed a high fat diet (45% fat) for 5 weeks so that obesity was led intentionally. Then, these obese mice were divided into 2 groups: control group (CON. n10) or exercise group (EXE, n=l0). EXE performed treadmill running for 30-60 min/day at 10-22 m/min, 0% grade, five times per week for 8 weeks. After 13 weeks, all the splenocyte was collected and Con A (Concanvalin A 10 ㎍/ml) was used to stimulate the cell proliferation. MTS and BIOPLEX assay were used for cell proliferation and cytokine production. Independent t-test was used and a p-value under 0.05 was considered as statistically significant. In the results, body weight, IL-2 and IL-6 production were significantly reduced and Splenocyte proliferation was significantly increased after 8 weeks of exercise training. These findings suggest that aerobic exercise training has a positive effect for improving the obese-induced immune dysfunction.
패브리병(Fabry) 진단을 위한 혈장 중 Globotriaosylceramide (Gb3)의 탠덤매스 분석법 개발과 임상 응용
Yoon, Hye-Ran,Cho, Kyung-Hee,Yoo, Han-Wook,Choi, Jin-Ho,Lee, Dong-Hwan,Zhang, Kate,Keutzer, Joan 대한의학유전학회 2007 대한의학유전학회지 Vol.4 No.1
목 적 : 패브리병은 X-linked 지질 축적 질환으로 ${\alpha}$-galactosidase A (${\alpha}$-Gal A)의 결손으로 인해 스핑고당지질인 Gb3의 세포내 축적을 일으키는 병이다. 혈장 중 Gb3 측정은 패브리병 환자의 효소대체요법 후의 모니터링이나 진단에 임상적 의의가 크므로 ESI-MS/MS를 이용한 시료 전처리를 위한 노동력이 덜 들면서 간단, 신속, 고감도로 정량할 수 있는 혈장 중 Gb3분석법을 개발하고자 하였다. 방 법 : 혈장을 디옥산으로 50배 희석하여 vortex-mix 및 원심분리를 거쳐 Gb3의 추출 및 분리를 수행한다. 이 때 내부표준액인 C17:0 Gb3를 혈장에 처음부터 첨가한다. 희석과 원심분리된 혈장은 가드컬럼을 통하여 ESI-MS/MS의 다중성분 모니터링 모드에서 분석하여 내부표준액에 대한 8종 Gb3 isoform의 피크면적비를 이용하여 정량한다. 결 과 : 혈장의 바탕성분 하에서 8종의 Gb3 isoform이 완전히 잘 분리됨을 확인할 수 있었다. 혈장 중의 8종의 Gb3 isoform 중 50% 이상 차지하는 종류는 C16:0 Gb3 임이 확인되었다. Gb3 isoform이 직선성을 이루는 농도 범위는 0.001-1.0 ${\mu}g$/mL이었다. 검출한계(S/N=3)는 C16:0 Gb3의 경우 0.001 ${\mu}g$/mL 이었고 정량한계는 0.01 ${\mu}g$/mL 이었으며 회수율의 일내재현성(정확도 87-108%와 정밀도 7% 이하)과 일간재현성(정확도 87-110%와 정밀도 13% 이하)은 매우 양호 하였다. 결 론 : 본 연구에서 개발된 Gb3 분석법은 신속, 정확, 간편하게 패브리병의 1차 스크리닝이나 효소대체요법 전후의 모니터링 및 진단에 유용하게 적용될 수 있을 것이다. Purpose : A simple, rapid, and highly sensitive analytical method for Gb3 in plasma was developed without labor-ex tensive pre-treatment by electrospray ionization MS/ MS (ESI-MS/MS). Measurement of globotriaosy lceramide (Gb3, ceramide trihex oside) in plasma has clinical importance for monitoring after enzyme replacement therapy in Fabry disease patients. The disease is an X-linked lipid storage disorder that results from a deficiency of the enzyme ${\alpha}$-galactosidase A (${\alpha}$-Gal A). The lack of ${\alpha}$-Gal A causes an intracellular accumulation of glycosphingolipids, mainly Gb3. Methods : Only simple 50-fold dilution of plasma is necessary for the extraction and isolation of Gb3 in plasma. Gb3 in diluted plasma was dissolved in dioxane containing C17:0 Gb3 as an internal standard. After centrifugation it was directly injected and analyzed through guard column by in combination with multiple reaction monitoring mode of ESI-MS/MS. Results : Eight isoforms of Gb3 were completely resolved from plasma matrix. C16:0 Gb3 occupied 50% of total Gb3 as a major component in plasma. Linear relationship for Gb3 isoforms w as found in the range of 0.001-1.0 ${\mu}g$/mL. The limit of detection (S/N=3) was 0.001 ${\mu}g$/mL and limit of quantification was 0.01 ${\mu}g$/mL for C16:0 Gb3 with acceptable precision and accuracy. Correlation coefficient of calibration curves for 8 Gb3 isoforms ranged from 0.9678 to 0.9982. Conclusion : This quantitative method developed could be useful for rapid and sensitive 1st line Fabry disease screening, monitoring and/or diagnostic tool for Fabry disease.
Glioblastoma Cellular Origin and the Firework Pattern of Cancer Genesis from the Subventricular Zone
Yoon, Seon-Jin,Park, Junseong,Jang, Dong-Su,Kim, Hyun Jung,Lee, Joo Ho,Jo, Euna,Choi, Ran Joo,Shim, Jin-Kyung,Moon, Ju Hyung,Kim, Eui-Hyun,Chang, Jong Hee,Lee, Jeong Ho,Kang, Seok-Gu The Korean Neurosurgical Society 2020 Journal of Korean neurosurgical society Vol.63 No.1
Glioblastoma (GBM) is a disease without any definite cure. Numerous approaches have been tested in efforts to conquer this brain disease, but patients invariably experience recurrence or develop resistance to treatment. New surgical tools, carefully chosen samples, and experimental methods are enabling discoveries at single-cell resolution. The present article reviews the cell-of-origin of isocitrate dehydrogenase (IDH)-wildtype GBM, beginning with the historical background for focusing on cellular origin and introducing the cancer genesis patterned on firework. The authors also review mutations associated with the senescence process in cells of the subventricular zone (SVZ), and biological validation of somatic mutations in a mouse SVZ model. Understanding GBM would facilitate research on the origin of other cancers and may catalyze the development of new management approaches or treatments against IDH-wildtype GBM.
( Hee Seung Hong ),( Jiwon Baek ),( Jae Chul Park ),( Ho-su Lee ),( Dohoon Park ),( A-ran Yoon ),( Soo Jung Park ),( Sung Noh Hong ),( Seong-joon Koh ),( Chang Kyun Lee ),( Bo-in Lee ),( Sung Wook Hwa 대한소화기기능성질환·운동학회 2022 Gut and Liver Vol.16 No.6
Background/Aims: Chronic enteropathy associated with SLCO2A1 gene (CEAS), an inherited disease characterized by nonspecific intestinal ulcers, has emerged in the Japanese population via loss-of-function mutations in the SLCO2A1 gene. We aimed to investigate the clinical and genetic characteristics of Korean patients diagnosed with CEAS. Methods: From July 2018 to July 2021, we performed Sanger sequencing of the SLCO2A1 gene in 46 patients with chronic intestinal ulcers. CEAS was confirmed based on known SLCO2A1 mutations. We summarized the clinical characteristics of patients with confirmed CEAS. Results: Fourteen out of 46 patients (30.4%) had genetically confirmed CEAS, and two SLCO2A1 variants were detected (splicing site variant c.940+1G>A and nonsense mutation [p.R603X] in SLCO2A1). Twelve patients (85.7%) were females and the median age at diagnosis of CEAS was 44.5 years. All patients presented with abdominal pain, and 13 patients (92.9%) presented with anemia (median hemoglobin, 9.6 g/dL). Ten patients (71.4%) had hypoalbuminemia (median, 2.7 g/dL). The most commonly involved site was the ileum (13/14, 92.9%). Manifestations of primary hypertrophic osteoarthropathy (PHO), such as digital clubbing, pachydermia, and periostosis were observed in five patients (28.6%) and two male patients and one female patient satisfied all major PHO diagnostic criteria. Conclusions: The clinical and genetic characteristics of Korean patients with confirmed CEAS were similar to those reported in the literature. CEAS should be considered in the differential diagnosis for patients with unexplained chronic nonspecific ulcers of the small intestine. (Gut Liver 2022;16:942-951)