고포도당이 백서 사구체 메산지움 배양세포에서 p38 MAPK 활성화 및 Fibronectin 생성에 미치는 영향

유태현 ( Yu Tae Hyeon ),허종호 ( Heo Jong Ho ),류동열 ( Lyu Dong Yeol ),김현욱 ( Kim Hyeon Ug ),이수현 ( Lee Su Hyeon ),김진주 ( Kim Jin Ju ),정동섭 ( Jeong Dong Seob ),최규헌 ( Choe Gyu Heon ),이호영 ( Lee Ho Yeong ),한대석 ( Han 대한신장학회 2003 Kidney Research and Clinical Practice Vol.22 No.5

목 적 : 고포도당으로 자극한 백서 메산지움 배양세포에서 p38 mitogen activated protein kinase (MAPK)의 활성화와 p38 MAPK의 상부와 하부인자로 알려져 있는 MAPK kinase 3/6 (MKK3/6)와 c-AMP responsive element binding protein (CREB)의 활성화, 그리고 fibronectin 합성을 자극 시간에 따라 관찰하고, p38 MAPK 경로와 fibronectin 합성 사이의 연관성을 규명함으로서 당뇨병성 신증의 병태생리를 규명하고자 하였다. 방 법 : 백서 메산지움 배양세포를 정상 포도당 (5.6 mM), 고포도당 (30 mM), 또는 정상 포도당+만니톨 (24.4 mM)로 자극한 후 첫째 p38 MAPK; 둘째 p38 MAPK의 상부 인자인 MKK3/6; 셋째 p38 MAPK의 하부인자인 CREB; 넷째 MAPK phosphatase-1 (MKP-1)의 변화를 자극 시간 (3분-48시간)에 따라 Western blot을 이용하여 관찰하였으며, 다섯째 fibronectin의 변화는 RT-PCR과 ELISA를 이용하여 확인하였다. 결 과 : 고포도당으로 자극한 백서 사구체 메산지움 배양세포에서 p38 MAPK 경로가 활성화 되었다. Total p38 MAPK 단백은 변화가 없었으나, 활성화된 phospho-p38 MAPK 단백은 고포도당군에서 자극 10분 후부터 정상 포도당군에 비해 의의있게 증가되었으며 (평균 1.9배), phospho-CREB 단백 역시 고포도당군에서 자극 10분 후부터 의미있게 증가되었다 (평균 2.5배). 이에 비해 p38 MAPK의 상부인자인 phospho-MKK3/6는 고포도당군에서 자극 3분 후부터 의의있게 증가되었다 (평균 2.4배). 또한, MKP-1 단백 발현은 고포도당군에서 p38 MAPK의 활성이 증가하기 시작한 시기와 동일한 시기 (자극 10분 후)부터 증가하기 시작하였다 (평균 1.9배). Fibronectin mRNA와 세포 배양액내 fibronectin은 고포도당군에서 자극 48시간 후에 각각 1.7배와 1.5배 증가되었으며, 이러한 증가는 p38 MAPK 억제제인 SB203580 (1 μM)에 의해 각각 73%와 69% 억제되었다. 결 론 : 고포도당으로 자극한 백서 사구체 메산지움 배양세포에서 p38 MAPK 경로의 활성화를 확인하였으며, p38 MAPK 억제제가 고포도당에 의한 fibronectin의 합성 증가를 억제시키는 것으로 보아 당뇨병성 신증에서 관찰되어지는 fibronectin의 축적에 p38 MAPK 경로가 관여할 것으로 생각된다. Background : The p38 mitogen-activated protein kinase (MAPK) pathway is activated by several stress factors, potentially leading to cellular apoptosis and growth. Little is known about the pattern of p38 MAPK pathway activation in mesangial cells under high glucose conditions. We examined the activity and expression of p38 MAPK members, 1x78 MAPK, MAPK kinase 3/6 (MKK3/6), c-AMP responsive element binding protein (CREE), and MAPK phosphatase-l (MKP-1) in cultured rnesangial cells exposed to high glucose. Methods : Mesangial cells were subcultured from rat glomeruli isolated by sieving technique. After serum restriction for 48 hours rnesangial cells were exposed to 5.6 mM glucose (low glucose, LG), 5.6 mM glucose+24.4 mM mannitol (LG+M), or 30 mM glucose (high glucose, HG) for 3 minutes to 48 hours with or without SU203580. Western blot was performed to determine the activity and protein expression of p38 MAPK members. R`I-I`CR and ELISA were performed for fibronectin mRNA expression and fibronectin synthesis, respectively. Results : p38 MAPK and CREB activities were significantly increased in rnesangial cells exposed to FIG compared with LG or LG+M after 10 minutes and was sustained at higher levels to 48 hours (p<0.05), but total p38 MAPK and CREB protein expressions did not differ. MKP--1 showed a similar pattern as p 3 MAPK and CREE (p<O.O.i). MKK3/6 acitvity was significantly higher in HG cells after 3 minutes and remained at higher levels throught the study period (p<0.05). Fibronectin mRNA expression and fibronectin synthesis were significantly increased in mesangial cells exposed to HG after 48 hours (p<0.05). SB203580 (1 pM) pretreatment for 1 hour significantly reduced HG-induced fibronectin mRNA expression and fibronectin synthesis by 73% and 69%, respectively (p<0.05). Conclusion : p38 MAPK activity was increased in mesangial cells exposed to HG in parallel with increased MKK3/6 activity, resulting in CREB activation and increased fibronectin synthesis. This activated p38 MAPK may play a role in the pathogenesis of diabetic nephropathy.

정신분열병과 Neuregulin 1 유전자의 연합연구

박동연,이유상,조은영,조승희,장용이,전현옥,장수연,윤세창,김종원,홍경수 大韓神經精神醫學會 2005 신경정신의학 Vol.44 No.3

Objectives : The authors recently found a suggestive evidence of linkage of chromosome 8p21-12 to schizophrenia in Korean multiplex families. Neuregutin 1 (NRGI) was identified in this locus as a positional and functional candidate gene for Schizo-phrenia, through several independent studies with European and Chinese populations. The purpose of this study is to determine whether NRGl is associated with schizophrenia in Korean population. Methods : Three SNPs (SNP8NRG221533, SNP8NRG241930, SNP8NRG243177) and two microsatellites markers (478B14-848,420M9-1395) located at the 5' end of NRGI were genotyped for 242 unrelated schizophrenia patients and the same num-ber of normal controls. Genetic association was tested by χ²-test (df=1). Not only for the whole patients group but also for asubgroup of patients with auditory hallucination. This subtype showed stronger linkage with chromosome 8p12 in the prior study of the authors with multiplex families. Results : G allele of SNP8NRG241930 was significantly in excess in the subgroup of patients with auditory hallucination compared to the control group (p=0.03, 0R=1.76). We also found that 3 SNPs haplotype TTC (p=0.04, 0R=0.58) and five markers haplotype TTC53 (p=0.01,0R=0.49) were associated with schziophrenia with a protective effect. Three SNPs haplotype CGT which is a part of the at-risk haplotype of the Icelandic schizophrenia families was found in excess in the patients group but no significant association was observed. Conclusion : NRGI might either play a mle in the predisposition to schizophrenia or be in linkage disequilibrium with a causal locus of this illness.

히스토아크릴을 이용한 십이지장 궤양 출혈의 지혈 후 발생한 급성췌장염

유재훈,문원,노지훈,구동영,조영화,김기수,윤준모 고신대학교 의과대학 2010 고신대학교 의과대학 학술지 Vol.25 No.1

Upper gastrointestinal bleeding is common and potentially life threatening medical emergency. Emergency endoscopy is the first choice of diagnostic and treatment measure for patients with active upper gastrointestinal bleeding. Histoacryl should be considered a second-line treatment modality when conventional treatments were failed. However, it might cause several complications. Herein, we report a case of acute pancreatitis developed after histoacryl injection therapy for active duodenal ulcer bleeding. A 71-year-old man was admitted with melena and hematemesis. On emergency endoscopy, a 2 cm sized active ulcer with bleeding from an exposedvessel was seen at the duodenal bulb. Attempts to arrest the bleeding with hemoclipping and submucosal epinephrine injection were tried, but failed. We changed the method to endoscopic histoacryl injection, and obtained hemostasis immediately. A few hourslater, after successful hemostasis, patient complained diffuse abdominal pain. Ultrasonography revealed hyperechoic heterogenous diffuse pancreatic enlargement and right pararenal space fluid collection, this ultrasonographic findings and elevated serum pancreatic enzymes are compatible with acute pancreatitis.

녹동균 세포외막 단백질 백신 CFC-1-101의 안정성 및 면역원성 검토 : 임상 제 Ⅰ/Ⅱa상 시험

장인진,김익상,유경상,임동석,김형기,신상구,장우현,박완제,이나경,정상보,안동호,조양제,안보영,이윤하,김영지,남성우,김현수 대한감염학회 1998 감염 Vol.30 No.3

목적 : 제일제당에서는 녹농균의 세포외막 단밸질을 유효성분으로 하는 백신인 CFC-101을 개발하였으며, 동물시험에서 이 백신의 안전성과 유효성을 입증하였다. 본 연구에서는 이 녹농균 백신의 인체에 대한 안전성과 면역원성을 평가하는 동시에 인체 접종시의 최적 투여 용량을 결정하기 위하여 제 I/Ⅱa상 임상시험을 수행하였다. 방법 : 건강한 성인 남자를 피험자로 선별하여 각 용량군에 백신투여자 6명, 위약투여자 2명을 배정하였다. 백신 투여군은 0.25mg, 0.5mg 또는 1.0mg 용량의 녹농균 백신을 7일 간격으로 3회에 걸쳐 근육주사 하였으며, 위약 투여군에게는 세포외막 단백질을 제외한 동일한 성분을 투여하였다. 백신접종 후 국소적 또는 전신적인 반응의 발생여부를 관찰하고, 혈액시료를 체취하여 백신의 역가와 유효성을 검정하였다. 결과 : 녹농균 백신 CFC-101은 모든 접종자에서 양호한 내약성을 보였다. 또한 0.5mg 과 1.0mg 백신 투여군에서는 100%의 항체양전율을 나타내었다. 생성된 항체는 녹농균 세포외막단백질에 특이성을 보였고, 녹농균 감염에 대해 방어효능이 있었다. 결론 : 이와같은 결과로부터 이 녹농균 백신은 인체에 안전하게 투여할 수 있으며, 높은 항체 생성능으로 감염방어 효능을 보이고 0.5mg과 1.0mg이 최적용량인 것으로 판단되었다. Background : We developed a Pseudomonas aeruginosa outer membrane protein(OMP) vaccine CFC-101, and the prophylactic efficacy of which has been demonstrated in animal models. In order to evaluate the safety and immunogenicity of the P. aeruginosa vaccine, we carried out a phase I/Ⅱa clinical trial in healthy male volunteers. Methods : Groups of eight volunteers, including two placebo subjects, were vaccinated intramuscularly with three doses of 0.25, 0.5 or 1.0 mg of the vaccine at one week intervals. Sings of systemic and local reactions observed after vaccination were recorded for each vaccinee for 5 days. Physical examinations were performed on days 0, 1, 7, 8, 14, 15, 21, and 42, and clinical laboratory tests were done on days 0, 3, and 21. Blood samples for assay of serum antibody levels were obtained up to 42 days after the first vaccination. Results : The vaccine was generally well tolerated by all vaccinees, showing no significant side effects. In the three dosage groups, all vaccinees, except one receiving the 0.25 mg dose, showed significant elevation in serum IgG antibody titers against the vaccine proteins, indicating 100% seroconversion in 0.5 and 1.0 mg groups. The human antibodies induced by the vaccine were specific for P. aeruginosa OMPs, as confirmed by western blot analysis and immunoprecipitation assays. The capacity of the human antisera to enhance opsonophagocytic killing activity by polymorphonuclear leukocytes and to confer protection against P. aeruginosa infections indicates that the antibodies elicited by the vaccine have protective efficacy. Conclusion : We conclude that the P. aeruginosa OMP vaccine is safe and effective for human use and its optimal dose to be 0.5 or 1.0 mg.

동종 조혈모세포이식 후 발생한 크립토콕쿠스 척추염 1예

고윤호,임동준,이성수,조유경,이동건,최정현,김유진,민창기,김동욱,박정미,김춘추,신완식 대한감염학회 2001 감염 Vol.33 No.4

Skeletal cryptococcosis is an uncommon infection. Cryptococcus is a common cause of meningitis and infects 7∼10% of patients with AIDS. As well as AIDS, the infection may be seen in association with leukemia, lymphoma, Hodgkin's disease, sarcoidosis, tuberculosis and diabetes, also in patients on steroid medication. But there is no case report of skeletal cryptococcosis following allogeneic hematopoietic stem cell transplantation. A 40-year-old woman was admitted to the hospital because of low back pain. She had chronic myelogenous leukemia for 2 years and underwent allogeneic hematopoietic stem cell transplantation 8 months ago. She have been treated with steroid and cyclosporine orally because of chronic graft versus host disease. On examination she was afebrile and had posterior lower lumbar tenderness. But, she had no reduced strength of low extremities. Open biopsy was underwent. Histology demonstrated budding, round-to-oval, refractile yeast-like organisms within debris. The results of a lumbar puncture were unremarkable and cerebrospinal fluid culture failed to grow bacteria and yeast. The patient was treated with amphotericin B (1 gram) and AmBisome□ (2.8 gram) over 6 weeks. Three months after cessation of therapy, the patient was doing well.(Korean J Infect Dis 33:298∼301, 2001)

한국판 해밀턴 우울증평가척도(K-HDRS)의 확인적 요인 분석

박혜원,이은호,김도관,유범희,이동수,김지혜 大韓神經精神醫學會 2009 신경정신의학 Vol.48 No.1

Objectives The present study was conducted to examine the factor structure of a Korean version of the Hamilton Depression Rating Scale (K-HDRS), and we did so by performing a confirmatory factor analysis (CFA). Methods The data from the 17-item K-HDRS data was obtained from 319 South Koreans who met the DSM-IV Criteria of Major Depressive Disorder. We examined the fit of ten competing models. The CFAs were evaluated in their original first-order structures and in their hierarchically related counterparts. Results The alternative models obtained unsatisfactory fit indices, although the five-factor inter-correlated model (model 5a) demonstrated a relatively good fit to the data. The model 5a also performed better than its hierarchically related counterpart (model 5b). The Modification Indices (MIs) were used to provide a more satisfactory account of the data. The Mls suggested correlations between the unique variances of items (item 1 & 3, item 10 & 15), and these parameters were added to the model 5a. After introducing minor modifications, the 'final' model (5m) yielded an improved model fit. Conclusion This study suggests that the symptoms of depression, as assessed by the K-HDRS, cluster into five factors : anhedonia/retardation, guilt/agitation, bodily symptoms, insomnia and appetite. This study provides evidence for the cross-cultural generalizability of the HDRS, although some refinement of the scale is still required.

[PC-0001] A Statistical Study of Phenotypic Diversity Based on Genetic Traits in Barley

Dong Su Yu(Dong Su Yu),Myoung-Jae Shin(Myoung-Jae Shin),Jin-Cheon Park(Jin-Cheon Park),Manjung Kang(Manjung Kang) 한국육종학회 2022 한국육종학회 공동학술발표집 Vol.2022 No.-

VBioindex: A Visual Tool to Estimate Biodiversity

Yu, Dong Su,Yoo, Seung Hwa Korea Genome Organization 2015 Genomics & informatics Vol.13 No.3

Biological diversity, also known as biodiversity, is an important criterion for measuring the value of an ecosystem. As biodiversity is closely related to human welfare and quality of life, many efforts to restore and maintain the biodiversity of species have been made by government agencies and non-governmental organizations, thereby drawing a substantial amount of international attention. In the fields of biological research, biodiversity is widely measured using traditional statistical indices such as the Shannon-Wiener index, species richness, evenness, and relative dominance of species. However, some biologists and ecologists have difficulty using these indices because they require advanced mathematical knowledge and computational techniques. Therefore, we developed VBioindex, a user-friendly program that is capable of measuring the Shannon-Wiener index, species richness, evenness, and relative dominance. VBioindex serves as an easy to use interface and visually represents the results in the form of a simple chart and in addition, VBioindex offers functions for long-term investigations of datasets using time-series analyses.

SFannotation: A Simple and Fast Protein Function Annotation System

Yu, Dong Su,Kim, Byung Kwon Korea Genome Organization 2014 Genomics & informatics Vol.12 No.2

Owing to the generation of vast amounts of sequencing data by using cost-effective, high-throughput sequencing technologies with improved computational approaches, many putative proteins have been discovered after assembly and structural annotation. Putative proteins are typically annotated using a functional annotation system that uses extant databases, but the expansive size of these databases often causes a bottleneck for rapid functional annotation. We developed SFannotation, a simple and fast functional annotation system that rapidly annotates putative proteins against four extant databases, Swiss-Prot, TIGRFAMs, Pfam, and the non-redundant sequence database, by using a best-hit approach with BLASTP and HMMSEARCH.

Algorithm for Predicting Functionally Equivalent Proteins from BLAST and HMMER Searches

( Yu Dong Su ),( Dae Hee Lee ),( Seong Keun Kim ),( Choong Hoon Lee ),( Ju Yeon Song ),( Eun Bae Kong ),( Jihyun F Kim1 ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.8

In order to predict biologically significant attributes such as function from protein sequences, searching against large databases for homologous proteins is a common practice. In particular, BLAST and HMMER are widely used in a variety of biological fields. However, sequencehomologous proteins determined by BLAST and proteins having the same domains predicted by HMMER are not always functionally equivalent, even though their sequences are aligning with high similarity. Thus, accurate assignment of functionally equivalent proteins from aligned sequences remains a challenge in bioinformatics. We have developed the FEP-BH algorithm to predict functionally equivalent proteins from protein-protein pairs identified by BLAST and from protein-domain pairs predicted by HMMER. When examined against domain classes of the Pfam-A seed database, FEP-BH showed 71.53% accuracy, whereas BLAST and HMMER were 57.72% and 36.62%, respectively. We expect that the FEP-BH algorithm will be effective in predicting functionally equivalent proteins from BLAST and HMMER outputs and will also suit biologists who want to search out functionally equivalent proteins from among sequence-homologous proteins.