Discovery of urinary metabolomic biomarkers for early detection of acute kidney injury

Won, A Jin,Kim, Siwon,Kim, Yoon Gyoon,Kim, Kyu-Bong,Choi, Wahn Soo,Kacew, Sam,Kim, Kyeong Seok,Jung, Jee H.,Lee, Byung Mu,Kim, Suhkmann,Kim, Hyung Sik The Royal Society of Chemistry 2016 Molecular bioSystems Vol.12 No.1

<P>The discovery of new biomarkers for early detection of drug-induced acute kidney injury (AKI) is clinically important. In this study, sensitive metabolomic biomarkers identified in the urine of rats were used to detect cisplatin-induced AKI. Cisplatin (10 mg kg(-1), i.p.) was administered to Sprague-Dawley rats, which were subsequently euthanized after 1, 3 or 5 days. In cisplatin-treated rats, mild histopathological alterations were noted at day 1, and these changes were severe at days 3 and 5. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at days 3 and 5. The levels of new urinary protein-based biomarkers, including kidney injury molecule-1 (KIM-1), glutathione S-transferase-alpha (GST-alpha), tissue inhibitor of metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, neutrophil, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin, were significantly elevated at days 3 and 5. Among urinary metabolites, trigonelline and 3-indoxylsulfate (3-IS) levels were significantly decreased in urine collected from cisplatin-treated rats prior to histological kidney damage. However, carbon tetrachloride (CCl4), a hepatotoxicant, did not affect these urinary biomarkers. Trigonelline is closely associated with GSH depletion and results in insufficient antioxidant capacity against cisplatin-induced AKI. The predominant cisplatin-induced AKI marker appeared to be reduced in urinary 3-IS levels. Because 3-IS is predominantly excreted via active secretion in proximal tubules, a decrease is indicative of tubular damage. Further, urinary excretion of 3-IS levels was markedly reduced in patients with AKI compared to normal subjects. The area under the curve receiver operating characteristics (AUC-ROC) for 3-IS was higher than for SCr, BUN, lactate dehydrogenase (LDH), total protein, and glucose. Therefore, low urinary or high serum 3-IS levels may be more useful for early detection of AKI than conventional biomarkers.</P>

항암제 처리한 백혈병 세포주에서의 Apoptosis 발현

김삼용,윤소현,김현수,김종숙,윤환중,김진경,조덕연 충남대학교 암연구소 1998 癌共同硏究所 硏究誌 Vol.2 No.1

The bcl-2 proto-oncogene encodes a 26 kD protein that promotes cell survival by blocking apoptosis. The bax protein is a member of the bcl-2 familly, now known to form heterodimers with the bcl-2 protein. The ratio of bax to bcl-2 is be critical in determining the fate of the cell in response to stimuli that can induce apoptosis. Extract of Pulsatilla Koreana (SB-31) showed promising antitumor activity in vitro with Topo I inhibitory action. In the present study, the relationship between apoptosis and the apoptosis related proteins, bcl-2 and bax were investigated in human leukemic cell lines HL-60, U-937 and CEM-CM3. All anticancer drugs(adriamycin, etoposide, camptothecin, SB-31) induced extensive apoptosis in HL-60, U-937 cells and CEM-CM3 cells. The expression of bcl-2 and bax protein were determined in cell lines by western blotting before and after incubation with anticancer drugs at different time points. 1) In HL-60 or U-937 cell lines, down regulation of bcl-2 and up-regulation of bax were found after incubation with ADR, VP-16 or camptothecin. 2) In HL-60 or U-937 cell lines, no significant change in bcl-2 or bax protein expression resulted after incubation with SB-31. 3) In CEM-CM3 cells, virtually no change was noted in bcl-2/bax expression after incubation with ADR, VP-16, camptothecin or SB-31. It is suggested that different leukemic cell lines use different pathways of apoptosis activation and a given cell may utilize different pathways of apoptosis activation in response to different cytotoxic agents.

구강외과 수술용 스텐트 기반 영상유도 수술 시스템의 개발

이우진,김대승,이원진,이삼선,최순철,허민석,허경회,김명진,이지호 대한구강악안면방사선학회 2009 Imaging Science in Dentistry Vol.39 No.3

Purpose : The purpose of this study was to develop a stent-based image guided surgery system and to apply it to oral and maxillofacial surgeries for anatomically complex sites. Materials and Methods : We devised a patient-specific stent for patient-to-image registration and navigation. Threedimensional positions of the reference probe and the tool probe were tracked by an optical camera system and the relative position of the handpiece drill tip to the reference probe was monitored continuously on the monitor of a PC. Using 8 landmarks for measuring accuracy, the spatial discrepancy between CT image coordinate and physical coordinate was calculated for testing the normality. Results : The accuracy over 8 anatomical landmarks showed an overall mean of 0.56±0.16 mm. The developed system was applied to a surgery for a vertical alveolar bone augmentation in right mandibular posterior area and possible interior alveolar nerve injury case of an impacted third molar. The developed system provided continuous monitoring of invisible anatomical structures during operation and 3D information for operation sites. The clinical challenge showed sufficient accuracy and availability of anatomically complex operation sites. Conclusion : The developed system showed sufficient accuracy and availability in oral and maxillofacial surgeries for anatomically complex sites. (Korean J Oral Maxillofac Radiol 2009; 39 : 149-56)

생산성 향상을 위한 생산 관리 시스템

김영진,오삼권,임기욱 호서대학교 반도체제조장비국산화연구센터 2001 반도체장비학술심포지움 Vol.2001 No.-

기업 내 관련 업무 및 조직의 유기적 연결을 통한 원활한 정보의 흐름은 생산성의 중대에 많은 영향을 주며 기업의 경쟁력과도 밀접한 관계가 있다.이러한 이유로 연구개발에서부터 설계, 제조, 판매에 이르기까지 컴퓨터와 통신기술을 활용하여 기업의 업무 흐름을 통합적으로 관리할 수 있는 컴퓨팅 시스템이 필요하다.그러나 기업 내 업무의 성격 및 규모, 어플리케이션 튜닝 등의 충분한 검토가 수행되지 않은 컴퓨팅 시스템은 개발비용의 부담과 더불어 시스템의 성능을 오히려 저하시킬 수 있다.본 논문은 생산 제조 업체의 업무의 성격과 환경에 적합하고 업무의 흐름을 유기적으로 통합 관리할 수 있는 클라이언트/서버 기반 생산 관리 시스템을 설계 및 구현하였다.

수출기업의 국제운송인 선정에 관한 연구방법론

김진삼,이기수 嶺南大學校附設 社會科學硏究所 1997 社會科學硏究 Vol.17 No.1

의원성 사고로 발생한 타액선염 : 증례보고

김현우,허경회,이원진,허민석,이삼선,최순철 대한구강악안면방사선학회 2004 Imaging Science in Dentistry Vol.34 No.2

A case of sialadenitis is presented in a patient with painful swelling of the right mouth floor. The condition was caused by trauma on the right mouth floor during dental treatment, which had happened 15 days before admission. On aspiration, mucous secretion was found and ultrasonography showed obstruction of duct. Histopathological studies and surgical investigation established a definite diagnosis of obstructive sialadenitis caused by ductal laceration. As surgical treatment sialodochoplasty was selected. The case and relevant considerations are discussed.

타이어축의 상하방향 진동과 자동차 실내소음과의 관계

김병삼,정진오 순천대학교 공업기술연구소 1997 工業技術硏究所論文集 Vol.11 No.-

Noise produced by vehicles affects daily lives, penetrating where man lives or works. Road noise of automobile is related to the axle vibration, and noise characteristics of automobile interior is also affected by the axle vibration. In this paper, a theoretical model is studied to describe the force transmissibility between road and tire axle vibration. The purpose of this paper is to investigate the relation between tire axle vibration and automobile interior noise experimentally. The results show that the frequency band of the interior noise is almost the same as that of the tire axle vibration. This implies that the reduction of tire axle vibration, through the change of vibration characteristics in tire can be useful for reduction of automobile interior noise.

實效保護關稅率 測定 模型의 有意性에 대한 比較分析

金鎭三 嶺南大學校附設 社會科學硏究所 1992 社會科學硏究 Vol.12 No.1

實效保護理論에 있어서 非交易投入財 模型의 擴張

金鎭三 嶺南大學校附設 社會科學硏究所 1990 社會科學硏究 Vol.10 No.2

치수 및 치근단 질환에서의 단백분해효소 및 단백분해효소 억제제의 활성도에 관한 연구

김진우,임성삼 대한치과보존학회 2000 Restorative Dentistry & Endodontics Vol.25 No.4

It is known that injuries to the dentin have a corresponding inflammatory effect on the pulp and these inflammatory effects frequently result in pulpal pathoses due to progressive degradation of pulpal connective tissue. It was supposed that the tissue degradation in different inflammatory process was controlled by proteinase activity and antiproteinase activity. Therefore, the purpose of this study was to examine the pulp and periapical pathoses in terms of the activities of proteinase and proteinase inhibitor. 37 pulpal tissues were divided by clinical diagnostic criteria into normal pulp, acute inflamed pulp, and chronic inflamed pulp, and then those groups were subdivided by histopathological findings into 5 pulpal pathoses groups, i.e. normal pulp (P1, n=8), chronic pulpitis with fibrotic change (P2, n=2), chronic pulpitis with dystrophic calcification (P3, n= 11), chronic pulpitis with pulp abscess (P4, n=7), acute pulpitis with necrotic change (P5, n =4). 26 periapical tissues were also divided by ordinary histopathological findings into 3 periapical pathoses group, i.e., granuloma (A1, n=17), cyst (A2, n=2) and abscess (A3, n=7). The activities of proteinases (cathepsin G, MMP-3) and proteinase inhibitors (α1-AT, TIMP-1 and, SLPI) were evaluated by RT-PCR and immunohistochemical methods. The results were as follows. 1.Generally, the intensity of immunohistochemical staining of proteinases and proteinase inhibitors increased in P2 and P5 groups compared to P1 group. 2.The immunohistochemical stain of proteinases and proteinase inhibitors was intensely detected in P2 group, showing low inflammatory reaction and low tissue degradation, but it was reduced in P3 and P4 groups, showing severe tissue degradation. 3.The distribution of proteinases and proteinase inhibitors in pulpal pathoses was consistently presented by immunohistochemical staining, while the expression of proteinase and/or proteinase inhibitors mRNAs in pulpal pathoses was occasionally detected by RT-PCR methods 4.RT-PCR of proteinase and proteinase inhibitors was usually positive in P2, showing rare tissue degradation, but it was almost negative in P3 and P4, showing severe tissue degradation. 5.We presume that the reason why the level of proteinase and proteinase inhibitors was so sparse in RT-PCR method is due to the abrupt decrease of mRNA synthesis or degradation of synthesized mRNA of proteinase and/or proteinase inhibitors depend on the inflammatory reaction and/or on the degradation of pulp tissues(P3, P4). 6.Pulpal pathoses groups showed significant lower RT-PCR detection of proteinases and proteinase inhibitors than the periapical pathoses group(p<0.05), and there is no significant difference among the periapical pathoses groups(P>0.05).