• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2003년도 제2차 연례학술대회 발표논문집
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• pp.66-72
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• 2003

Toxicogenomics is now emerging as one of the most important genomics application because the toxicity test based on gene expression profiles is expected more precise and efficient than current histopathological approach in pre-clinical phase. One of the challenging points in Toxicogenomics is the construction of intelligent database management system which can deal with very heterogeneous and complex data from many different experimental and information sources. Here we present a new Toxicogenomics database developed as a part of 'Toxicogenomics for Efficient Safety Test (TEST) project'. The TEST database is especially focused on the connectivity of heterogeneous data and intelligent query system which enables users to get inspiration from the complex data sets. The database deals with four kinds of information; compound information, histopathological information, gene expression information, and annotation information. Currently, TEST database has Toxicogenomics information fer 12 molecules with 4 efficacy classes; anti cancer, antibiotic, hypotension, and gastric ulcer. Users can easily access all kinds of detailed information about there compounds and simultaneously, users can also check the confidence of retrieved information by browsing the quality of experimental data and toxicity grade of gene generated from our toxicology annotation system. Intelligent query system is designed for multiple comparisons of experimental data because the comparison of experimental data according to histopathological toxicity, compounds, efficacy, and individual variation is crucial to find common genetic characteristics .Our presented system can be a good information source for the study of toxicology mechanism in the genome-wide level and also can be utilized fur the design of toxicity test chip.

• 한국발생생물학회지:발생과생식
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• 제9권2호
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• pp.105-114
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• 2005

배아 줄기세포는 세포 치료 목적을 위한 재료로써 매우 큰 잠재력을 가지고 있으며, 이러한 잠재력의 실현을 위해서 세포의 운명에 결정적인 역할을 하는 요소들을 확인하고 특정 세포의 대량 생산을 위한 방법을 개발하여야 한다. 조혈과정은 폭넓게 연구되어 왔으며, 배아 줄기세포로부터 조혈세포의 분화는 lineage commitment에 관한 연구에 좋은 모델이 된다. 본 연구에서는, 두 종류의 마우스 배아 줄기세포주 TC-1과 B6-1를 이용하여 그 특성과 조혈세포 분화능을 비교하여 보았다. 두 세포주는 작은 차이는 있으나 줄기세포로서의 특성을 공통적으로 가지고 있었다. 그러나 methylcellulose 배양 system을 사용하여 embryonic body 형성능을 확인한 결과 TC-1이 B6-1에 비해 월등함을 확인하였다. 조혈세포 분화의 추적을 위해 blast colony의 형성, progenitor assay, RT-PCR을 통한 조혈세포 분화 관련 marker의 발현 분석을 수행한 결과, TC-1은 정상적으로 조혈세포를 생성해 내지만, B6-1은 제대로 분화되지 못함을 확인할 수 있었다. 이러한 결과들은 in vitro에서 배아 줄기세포로부터 조혈세포로 분화를 유도할 때, 보다 적합한 세포주의 탐색이 요구됨을 제시하며 이는 향후 인간 배아 줄기세포주에서도 마찬가지로 적용될 수 있음을 암시한다고 사료된다.

• Journal of Microbiology and Biotechnology
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• 제21권12호
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• pp.1345-1351
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• 2011

Vancomycin therapy failure due to the emergence of tolerance in pneumococci is increasing. The molecular mechanism of tolerance is not clear, but lytA and $pep^{27}$ are known to be involved. Our aim was to evaluate the expression of both genes in vancomycin-tolerant Streptococcus pneumoniae (VTSP) strains. Eleven VTSP strains from a total of 309 clinical isolates of S. pneumoniae from 1997 to 2006 were classified according to the criteria of Liu and Tomasz. All VTSP strains were evaluated for susceptibility according to CLSI criteria, serotype by the Quellung test, and clonality by PFGE. The expressions of lytA and $pep^{27}$ were analyzed in different growth phases by RT-PCR with and without vancomycin. Eighty-two percent of VTSP strains showed resistance to penicillin, and 100% were sensitive to vancomycin and cefotaxime. The most frequent serotypes of VTSP strains were 23F (4/11) and 6B (3/11). Clonal relationship was observed in only two strains. No significant changes were observed in $pep^{27}$ expression in the three phases of growth in VTSP strains with and without vancomycin. Interestingly, $pep^{27}$ expression in the stationary phase in the non-tolerant reference strain R6 was significantly higher. However, no significant differences in lytA expression were observed between VTSP and R6 strains during the phases of growth analyzed. The absence of changes in $pep^{27}$ expression in VTSP strains in the stationary phase may be related to their ability to tolerate high antibiotic concentrations, and thus, they survive and remain in the host under the antibiotic selective pressure reflected in therapeutic failure.

• Journal of Genetic Medicine
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• 제5권1호
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• pp.55-60
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• 2008

목 적 : 염색체 검사는 의학의 많은 영역과 혈액종양학 분야에서 중요한 역할을 하고 있다. 세포의 기능을 잘 유지하면서 장기간 보관할 수 있는 가장 효과적인 방법은 냉동보존(cryopreservation)으로 알려져 있으며, 이는 미래에 신기술을 적용할 수 있고 회귀연구를 가능하게 한다. 이에 본 연구에서는 제대혈에서 분리된 단핵세포의 냉동전과 해동후의 염색체 검사 결과를 비교하고자 한다. 방 법 : 실험에 대한 동의서를 획득한 제대혈 1례가 검사되었다. Ficoll-Hypaue로 단핵세포를 분리하였고, DMSO 등 냉동보존을 위한 전처리 후 프로그램 냉동기(Cryomed 1010, 미국)로 냉동하여 질소탱크($-196^{\circ}C$)에 3일간 보관하였고, 급속냉동 후 염색체 검사를 시행하였다. 냉동전과 해동후의 염색체 핵형을 분석하였다. 결 과 : 1례의 제대혈은 3군으로 나누어, 냉동 전 배양과정 없던 CB-1군은 염색체 핵형 검사가 판독 불가능하였으며, 냉동 전 3일간 배양 후 냉동보관을 하였던 CB-2와 CB-3군은 냉동전과 해동후의 염색체 핵형이 판독 가능하였고, 서로 일치하였다. 결 론 : 검체의 분포 불균형과 검체 수가 적다는 제한점이 있으나, 제대혈에서 냉동전과 해동후의 염색체 핵형이 일치하는 결과에서 제대혈 단핵세포의 유전적 안정성과 장기간 보관의 가능성을 예측할 수 있을 것으로 사료된다.

• Journal of Genetic Medicine
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• 제6권1호
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• pp.81-86
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• 2009

다발성 골단이형성증은 임상적 및 유전학적으로 이질적인 연골이형성증으로, 골화 중심의 발달 지연, 골단만을 침범하는 사지의 변형 및 경한 저신장을 보이는 질환이다. 원인으로는 COMP 유전자의 돌연변이가 가장 흔히 발견되고 있으며, 돌연변이의 대부분은 칼모듈린 유사 반복(calmodulin-like repeats)부분과 C-말단에 위치한다. 저자들은 4대에 걸쳐 12명의 가족구성원에서 다발성 골단이형성증을 보인 한 가계에서 COMP 유전자 분석으로 새로운 돌연변이를 발견하여 보고하는 바이다. 이 가계는 젊은 나이에 퇴행성 관절염이 발생하고, 추후 관절치환술이 요구되는 상염색체 우성 유전 방식을 보이는 질환을 가지고 있었다. 방사선학적 검사상 양측 무릎 관절의 내측 대퇴돌기에 골연골 결손을 보였으며, 양측 무릎과 엉덩이 관절은 다양한 정도의 퇴행성 변화가 관찰되었다. 계보발단자 및 5명의 다른 이환된 가족들에서 시행한 COMP 유전자 분석에서, 12번째 엑손에서 현재까지 보고되지 않은 새로운 돌연변이인 c.1280G>C (p.Gly427Ala)을 확인하였다. 이 돌연변이는 다른 3명의 이환되지 않은 가족들에서는 발견되지 않았다. 상염색체 우성 방식을 보이는 다발성 골단이형성증 환자들에서 COMP 유전자의 직접 염기서열 분석법은 질병의 원인이 되는 돌연변이를 찾는데 도움이 되며, 고위험 가족들에서 보인자를 찾아낼 수 있고, 질병의 합병증이 발생하기 이전에 조기 진단 및 중재를 가능케 하는 유전 상담의 기회를 제공해 줄 수 있다.

• Journal of Genetic Medicine
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• 제10권1호
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• pp.38-42
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• 2013

Purpose: The purpose of this study was to assess the characteristics of achondroplasia (ACH) diagnosed in fetuses or neonates and to evaluate the usefulness of a molecular genetic testing to confirm ACH. Materials and Methods: The medical and ultrasonographic records of 16 pregnant women, who had molecular genetic testing for ACH performed on their fetus or neonate at the Cheil General Hospital between February 1999 and April 2013, were retrospectively analyzed. Detection of G1138A and G1138C mutations of the fibroblast growth factor receptor 3 (FGFR3) gene was accomplished by polymerase chain reaction - restriction fragment length polymorphism analysis. Results: Of the eight fetuses and two neonates who were suspected of having ACH during pregnancy, four fetuses and one neonate was confirmed to have ACH and they all carried the heterozygous G1138A mutation. Out of 6 cases which had a history of ACH in prior pregnancies, three had genetic information for the previous fetuses while the other three did not. All six fetuses had no mutations at G380R. However, the one fetus of pregnant woman with non-confirmed ACH showed shortened long bone on ultrasound thereafter and the fetus was identified as having oto-spondylo-megaepiphyseal dysplasia after birth. Conclusion: Korean patients with achondroplasia have the heterozygous G1138A mutation that is most commonly defined in other countries. Molecular genetic evaluations of ACH are helpful not only for establishing diagnosis but for appropriate counseling with subsequent pregnancies.

• Genomics & Informatics
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• 제15권1호
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• pp.2-10
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• 2017

Early detection and proper management of kidney rejection are crucial for the long-term health of a transplant recipient. Recipients are normally monitored by serum creatinine measurement and sometimes with graft biopsies. Donor-derived cell-free deoxyribonucleic acid (cfDNA) in the recipient's plasma and/or urine may be a better indicator of acute rejection. We evaluated digital PCR (dPCR) as a system for monitoring graft status using single nucleotide polymorphism (SNP)-based detection of donor DNA in plasma or urine. We compared the detection abilities of the QX200, RainDrop, and QuantStudio 3D dPCR systems. The QX200 was the most accurate and sensitive. Plasma and/or urine samples were isolated from 34 kidney recipients at multiple time points after transplantation, and analyzed by dPCR using the QX200. We found that donor DNA was almost undetectable in plasma DNA samples, whereas a high percentage of donor DNA was measured in urine DNA samples, indicating that urine is a good source of cfDNA for patient monitoring. We found that at least 24% of the highly polymorphic SNPs used to identify individuals could also identify donor cfDNA in transplant patient samples. Our results further showed that autosomal, sex-specific, and mitochondrial SNPs were suitable markers for identifying donor cfDNA. Finally, we found that donor-derived cfDNA measurement by dPCR was not sufficient to predict a patient's clinical condition. Our results indicate that donor-derived cfDNA is not an accurate predictor of kidney status in kidney transplant patients.

• 대한한방내과학회지
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• 제28권2호
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• pp.284-293
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• 2007

Objectives : Hypertension(HTN), diabetes mellitus(DM) and hyperlipidemia(HL) are the most common risk factors of cerebro-vascular attack(CVA). To prevent CVA, early diagnosis (awareness before CVA) of HTN, DM and HL is essential, and for the effective early diagnosis we need to analyze the data of CVA patients concerned with HTN, DM and HL. In this study, we studied characteristics of patients early diagnosed before CVA. Methods : We analyzed the data of 363 patients with acute ischemic stroke from Hanbang Stroke Registry supported by the Ministry of Science and Technology of Korea. Subjects' enrollment was done in the oriental medical hospitals of 3 universities located in the metropolitan region from October 2005 to October 2006. We analyzed all registered data about HTN. DM and HL, for example, how many patients were aware of their HTN, DM or HL before CVA, differences in characteristics of early diagnosed patients, effects of early diagnosis on CAV, etc. Results : Patients aware of their HTN. DM and HL before CVA have more past history and family history about HTN, DM or HL. Early diagnosis rate of HL is lower than HTN and DM, and early diagnosed HL patients were younger and deucated longer than patients who weren't aware of their HL before CVA. These results mean that publicity is the key to promoting early diagnosis rates of HTN, DM and HL. In DM and HL, early diagnosed patients had more SVO type cerebral infarction than patients who weren't aware of risk factors. We can thus see that early diagnosis even affects CVA types. Conclusion : This work helps us to understand the realities and importance of early diagnosis of HTN, DM and HL before CVA. There should be further research, which can contribute to much more improved early diagnosis rates of HTN, DM and HL.

• Clinical and Experimental Reproductive Medicine
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• 제29권4호
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• pp.323-335
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• 2002

Object: The present study was accomplished to obtain a gene expression profile of the luminal epithelium during embryo apposition in comparison of implantation (1M) and interimplantation (INTER) sites. Material and Method: The mouse uterine luminal epithelium from IM and INTER sites were sampled on day 4.5 (Day of vaginal plug = day 0.5) by Laser Captured Microdissection (LCM). RNA was extracted from LCM captured epithelium, amplified, labeled and hybridized to microarrays. Results from microarray hybridization were analyzed by Significance Analysis of Microarrays (SAM) method. Differential expression of some genes was confirmed by LCM followed by RT-PCR. Results: Comparison of IM and INTER sites by SAM identified 73 genes most highly ranked at IM, while 13 genes at the INTER sites, within the estimated false discovery rate (FDR) of 0.163. Among 73 genes at IM, 20 were EST/unknown function, and the remain 53 were categorized to the structural, cell cycle, gene/protein expression, immune reaction, invasion, metabolism, oxidative stress, and signal transduction. Of the 24 structural genes, 14 were related especially to extracellular matrix and tissue remodeling. Meanwhile, among 13 genes up-regulated at INTER, 8 genes were EST/unknown function, and the rest 5 were related to metabolism, signal transduction, and gene/protein expression. Among these 58 (53+5) genes with known functions, 13 genes (22.4%) were related with $Ca^{2+}$ for their function. Conclusions: Results of the present study suggest that 1) active tissue remodeling is occurring at the IM sites during embryo apposition, 2) the INTER sites are relatively quiescent than IM sites, and 3) the $Ca^{2+}$ may be a crucial for apposition. Search for human homologue of those genes expressed in the mouse luminal epithelium during apposition will help to understand the implantation process and/or implantation failure in humans.

• Journal of Genetic Medicine
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• 제8권1호
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• pp.35-43
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• 2011

목적: 본원에서 최근 10년간 시행한 융모막 융모생검의 적응증에 따른 결과 및 합병증을 조사하고 현재 사용하고 있는 융모막 융모생검의 효용성을 분석해보고자 한다. 대상 및 방법: 2000년 4월부터 2010년 4월까지 최근 10년간 분당차병원 및 강남차병원에서 융모막 융모생검을 시행한 511례의 진료기록 및 검사 결과를 검토하였다. 각각의 환자에 해당되는 모든 적응증을 조사하고 중복을 허용하여 분석하였다. 태아 염색체 검사는 직접법과 배양법을 통하여 시행하였다. 결과: 각각의 적응증을 살펴보면 태아의 비후된 목덜미 두께를 포함한 비정상 초음파 소견이 294례(294/635, 46.3%)로 가장 높았다. 각각의 적응증에 따른 태아 염색체 이상의 양성예측도는 부모 중에 염색체 이상이 있는 경우가 66.7%(14/21)로 가장 높았다. 융모막 융모생검 상 모자이시즘은 3.1% (16/509)였고, 그 중에서 양수검사로 확인된 진모자이시즘은 2례, 태반에 국한된 모자이시즘은 11례였다. 융모막 융모생검 이후 4주 이내에 임신 종결된 경우는 6례로 태아손실률은 1.2% (6/511)였다. 결론: 융모막 융모생검은 산전 유전진단을 하는데 있어서 적합하고 신뢰할 수 있는 시술이다. 융모막 융모생검 결과 모자이시즘을 보이는 경우 반드시 양수검사를 통하여 진모자이시즘인지 태반에 국한된 모자이시즘인지 확인이 필요하다.