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>

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

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.

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.

혈관모세포종의 임상 분석

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

혈관모세포종의 임상 분석

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

상부위장관 출혈 원인의 변화 양상

김태년,도병수,김현정,이삼범,정문관 大韓應急醫學會 1999 대한응급의학회지 Vol.10 No.2

Upper gastrointestinal(UGI) bleeding was critical disease that was commonly found in emergency department and needed more early diagnosis and rapid treatment for decreasing mortality and morbidity. It's causes and frequencies were affected by many factors, but the majorities were caused by peptic ulcers and esophageal-gastric varices. With development of economy and medical services, new drugs and endoscopic interventions, the treatment of patients with UGI bleeding was more improved. So I would like to evaluate the change of causes and frequencies of UGI bleeding and the associated clinical findings. A total of 1,546 patients presented with UGI bleeding in emergency department of Yeungnam university hospital during the five years from Jan. 1991 to Dec. 1995 were clinically reviewed by chart and compared with previous seven years report from Jan. 1984 to Dec. 1990 in the same hospital. The ratio of male to female was 6.1:1 and slightly increased in comparison with previous seven years. The incidences in 6th and 5th decades were highest(54.4%)as like as previous seven years. Age distribution of duodenal ulcer bleeding, Mallory-Weiss tear and acute gastric mucosal lesion were developed in lower decades than the others. The causes of UGI bleeding were caused by esophageal varix(45.4%), peptic ulcer(38.8%), Mallory-Weiss tear(4.3%), gastric cancer(3.8%), other(3.1%), acute gastric mucosal lesion(2.7%), undetermined causes(1.8%) in descending order of frequencies. The proportion of esophageal varices was increased from 36.6% to 45.4%, but that of peptic ulcer was relatively decreased from 47.6% to 38.8%. And the annual distribution of varices was increased, however the annual distribution of peptic ulcers was increased. Although the ranking of annual distribution of gastric ulcers and duodenal ulcers were not changed compared to previous study and the frequency of gastric ulcers was increased since 1992, but additional follow-up was needed. Seasonal variations were found that upper gastrointestinal bleeding was increased in fall and peptic ulcer bleeding was increased significantly in summer and fall, however, varix bleeding was less frequent in summer time as like as previous seven years. Emergency endoscopic examination was performed within 6 hours for 54.5%, 24 hours for 90.8% and this results were to be like previous results, 57.5% and 90.7 respectively. Findings of emergency endoscopic examination were active bleeding focus(21.2%), blood clot(7.9%), exposed vessels(13.3%), flat blood spot(6.4%) and lesion without evidence of bleeding(51.3%). Endoscopic findings of active bleeding were easily seen when examination was perfomed within 24 hours. Blood transfusion was performed in 67.3% with average 2.1 units. When the causes of bleeding were due to varix and marginal ulcer, more amounts of blood were transfused than the others. In previous seven years, blood transfusions were performed in 71.2% with average 5 units and more amounts of blood were transfused in gastric cancer and varix bleeding.

在韓國 日本系 投資企業의 人事管理ㆍ勞使關係 : 事例調査 : 韓日比較의 視角에서

金三洙 韓日經商學會 1996 韓日經商論集 Vol.12 No.-

本稿は. 在韓日本系投資企業における人事管理および勞使關係の實態を解明するはめに製造業4社(電子部品2社,機械部品2社), サ-ビス業2社,計6社の企業を對象として事例調査をした. 調査企業の主要特徵は,つぎのように要約される. 第1に,大卒の事務·技術系と高卒以下の技能系=が徹底した位階秩序をもつ華直的な職種區分=職級體系となっている. 第2に,事務·技術系=月給制,技能系=日給制のように責任計算方式が差別的であり. とくに技能系の場合人事考課(調定)は適用されていない. 第3に. 職種區分が細分化されているが. 積極的な職務循環は行われていない. そして現場監督者の能力な低い水準にとどまっている. 第4に, 企業組織別組合であるが, 製造業の場合,事務技術系の一般職の加入は排除されている. 現場監督層の組合に對する影響力は大きく制限されている. いのような再韓日本系投資企業の人事管理および勞使關係の實態は, 職務區分の不定形性という本質的共通點にもかかれらず, 日本企業の定型化された諸特徵とはなお大もく異なる. 他方で, それは韓國大企業の勞使關係一般的とはそれほど差がない. 現段階の韓國の人事管理·勞使關係制度の核心に位置するのが,學力別に華直的な位階秩序をもつ職種=職級區分である. いの區分の??のいかがこれから韓國の勞使關係を形作る決定的な變數になると展望される.

이 심전도의 진단은?

김삼수 한국의학사 2004 診斷과治療 Vol.24 No.2

이 심전도의 진단은?

김삼수 한국의학사 2004 診斷과治療 Vol.24 No.4