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.

냉동 제대혈 세포의 체외 증폭

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

Background : Cord blood(CB), which has no HLA restriction, is an alternative to bone marrow for hematopoietic stem cell transplantation. The use of cord blood, however, is limited by the number of progenitor/stem cells necessary to reconstitute the older child or adult. Therefore, ex vivo expansion of CB could have tremendous impact on diverse clinical settings. We studied the ex vivo expansion of isolated population of CD34_(+) cells from cryopreserved CB cells. Methods : CD34 cells were isolated from cryopreserved CB mononuclear cells. Purified cells were cultured with various combinations of hematopoietic growth factors including erythropoietin(EPO), stem cell factor(SCF), granulocyte-colony-stimulating factor(G-CSF), gra-nulocyte, macrophage-colony-stimulating factor(GM-CSF), interleukin-1β(IL-1β), 1L-3, and IL-6. After 7, 10 or 14 days of culture, the fold increases of colony-forming unit- granu-locyte, macrophage(CFU-GM), burst-forming unit-erythroid(BFU-E), colony-forming unit-mix (CFU-Mix), and high proliferative potential colony-forming cell(HPP-CFC) were evaluated. Results : Ten-day culture with the combination of EPO, SCF, G-CSF, IL-1β, and IL-3 resulted in a median of 60-fold increase of CFU-GM, which was greater than those with the combinations of less than 5 growth factors. The addition of IL-6 or GM-CSF to this combination did not enhance CFU-GM expansion. Ten-day culture was significantly superior to 7-day culture for CFU-GM expansion. Prolongation of culture to 14 days, however, revealed decreased expansion of CFU-GM compared to 10 days. BFU-E and CFU-Mix were expanded to 2~5 folds in 7-day culture with the combination of EPO, SCF, and G-CSF. Further expansion was not achieved in 10-day culture and colonies disappeared in 14-day culture. HPP-CFC was expanded to a median of 7.5 folds in 7-day culture with the combination of EPO, SCF, G-CSF, IL-1β, IL-3, and IL-6. Neither 10-day or 14 day-culture enhanced expansion of HPP-CFU. Conclusion : Cryopreserved cord blood cells maintain ex vivo expansion potential. In our system, 10-day culture with the combination consisting of EPO, SCF, G-CSF, IL-1β, and IL-3 seems to be adequate for hematopoietic progenitor/stem cell expansion from cryopreserved cord blood cells.

치상 돌기 골절의 전방 경유 나사못 고정술 치료 성적

김인영,김수한,이정길,김태선,김재휴,이제혁,강삼석 대한신경외과학회 1997 Journal of Korean neurosurgical society Vol.26 No.9

혈관모세포종의 임상 분석

김은성,강삼석,이정길,김태선,정신,김재휴,김수한,이제혁 대한신경외과학회 1998 Journal of Korean neurosurgical society Vol.27 No.1

혈관모세포종의 임상 분석

김은성,강삼석,이정길,김태선,정신,김재휴,김수한,이제혁 대한신경외과학회 1998 Journal of Korean neurosurgical society Vol.27 No.5

이 심전도의 진단은?

김삼수 한국의학사 2004 診斷과治療 Vol.24 No.5

大黃水渡液이 물김치의 酸度變化에 미치는 影響

金英嬉,李正秀,蘇三燮,陳甲德 嶺南大學校 環境問題硏究所 1989 環境硏究 Vol.8 No.2

Effect of water and ethanol extract of Rheum coreanum N. on changes of pH in different NaC1 concentration and temperature in Juicy Kimchi was investigated and then, compared with it to sodium benzoate. The following results were obtained. 1. Addition of 0.03% water and ethanol extract of Rheum coreanum N. to juicy Kimchi preserved above pH 4.0 in whole experimental period at 30℃. 2. Addition of 0.1% water extract of Rheum coreanum N. induced less pH changes than control and preserved above pH 4.5 after 7 day at 18℃. 3. It was observed that water estract of Rheum coreanum N. was greater than ethanol extract in preservative potency. 4. Preservative potency of 0.03% water extract of Rheum coreanum N. was superior to 0.1% sodium benzoate. 5. Addition of 0.03% water extract of Rheum coreanum N. prolonged the tasty period of juicy Kimchi, which was more effective than sodium benzoate.

연약지반 성토시 사면의 안정에 미치는 Geotextile의 효과

김수일,조삼덕,우제윤 연세대학교 산업기술연구소 1982 논문집 Vol.14 No.2

Geotextiles have been extensively used in road constructions as effective and economical materials performing several functions such as separation, filtration, drainage, protection against frost break, and as reinforcement to improve the load bearing capacity and stability of road. In this study, a method for the analysis of embankment reinforced with geotextile is studied. Computer program based on the simplified Bishop method is modified in order to investigate quantitively the effect of gotextile on the slope stability of embankment on weak soils. Evaluation of the tensile strength required for the design safety factor is also possible utilizing the computer program in this study.

日本에서의 安定的 勞使關係의 成立

金三洙 서울産業大學校 1995 논문집 Vol.41 No.1

In this paper, I have analyzed the formation process and mechanism of “co-operative industrial relations” in Japan. It is pointed out that the co-operative labor-management relations in Japan is an historical outcome of the enterprise unionism, the change of the initiative of labor movements, the Japanese style foreman system and the wage bargaining System(“Spring Offensive”) which were executed during 1950's and 1960's. Especially the unique style and functions of shopfloor groups and foremen are analyzed as a core basis of the co-operative industrial relations.