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>

인천지역 TDI 노출 작업자에서 직업성천식 유병율

김형렬,김철우,홍윤철,전형준,김치년,김현수,이지나,신주연,고동희,노재훈 大韓産業醫學會 2004 대한직업환경의학회지 Vol.16 No.2

목적 : TDI는 직업성천식을 일으키는 대표적인 물질로 알려져 있다. 과거 TDI에 노출된 작업자들의 천식 발생률을 5~6%가량 보고하였고, 국내에서도 2-20%에 이르는 유병율을 보고한바 있다. 작업환경이 많이 개선되고, 노출량이 감소된 최근에도 TDI에 의한 직업성천식에 대한 보고가 많이 이루어지고 있어, 이에 대한 적극적인 조사와 진단과정을 통해 유병율을 구하고 질병발생의 변화양상을 파악해 보고자 하였다. 방법 : 인천지역에서 특수건강진단을 수행하는 2개 기관의 TDI 노출 근로자 400여명 중, 사업장의 규모가 50인 이상이며 사업주가 연구진행을 허락한 사업장에서 근무하는 근로자 중 직접적으로 TDI에 노출되는 작업에 종사하는 근로자 170명을 연구대상으로 하였다. 이들에 대해 설문지와 산업의학의사의 면담을 통한 작업관련성 평가를 근거로 정밀대상자를 선정하고 이들에 대해 메타콜린 유발시험, TDI 유발시험 등을 수행하여 직업성천식을 확인하였다. 결과 : 설문조사 결과 11명이 직업과 관련하여 천식증상을 보이는 것으로 나타났고(6.9%), 이중 7명에서 메타콜린 유발검사 양성소견을 보였다. TDI에 의한 특이유발시험 결과 1명에서 양성반응이 나타나, 이 집단에서 TDI에 의한 직업성천식의 유병율은 0.58%였다. 결론 : 과거 국내연구에서 TDI에 의한 직업성천식의 유병율이 2~20%에 이르렀던 데 비해, 본 연구에서는 0.58%로 나타났다. 이는 국외 논문에서도 나타나는 경향으로 작업장 노출량 감소로 점차 발생률이 감소하는 양상을 보이고 있다. 그러나 이미 증상이 나타난 근로자들이 부서를 옮기거나, 직장을 그만둠으로 인해 그 유병율이 과소평가되었을 가능성도 있다고 판단된다. Objecdives: This study was carried out to estimate the prevalence of isocyanate-induced occupational asthma in toluene diisocyanate (TDI) exposed workers. Methods: We examined 170 workers who had been directly exposed to TDI through a medical questionnaire, physical examination, and pulmonary function test. Based on screening examination, workers with suspected occupational asthma were selected for further evaluation such as methacholine and TDI challenge tests. Results: Eleven (6.9%) among 170 workers complained of symptoms of occupational asthma. and 7 among these 11 symptomatic workers showed positive responses to the methacholine challenge test (4.1 %). One spray painter was confirmed as having the TDI induced occupational asthma following a positive response to TDI challenge test. Conclusions: The prevalence of TDI-induced asthma was at 0.58% was lower than that for former studies (2-20%). Improved workplace environment, lower level of TDI exposure compared to the past, and the healthy workers effect may have contributed to this low rate of asthma prevalence in workers with TDI exposure.

당뇨병 환자에서 혈장 Thrombin-Antithrombin Ⅲ 및 Plasmin-α_2-Plasmin Inhibitor 복합체의 임상적 의의

김경욱,김은숙,정상수,윤수지,박우일,이준희,남수연,안철우,문병수,김경래,차봉수,송영득,임승길,이현철,허갑범 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.5

연구배경:당뇨병 환자에서 혈액응고 및 섬유소용해 체계의 이상경향이 있어 그 결과로 여러 혈관합병증의 발생위험이 높다는 사실은 널리 알려져 있다. 그 기전은 아직 확실히 밝혀지지 않았으나, 고혈당으로 인한 혈장 단백질들의 비효소성 당화작용이나 산화성 스트레스로 인한 유리 라티칼 작용으로 응고항진이나 섬유소용해 활성의 저하를 유발하는 것으로 생각되고 있다. 최근 응고 및 용해인자와 그 억제자의 복합체들의 증가가 이 상태를 비교적 예민하게 반영한다고 알려져 있다. 방법:본 연구에서는 당뇨병 환자 101명과 정상 대조군 20명에서 혈장내 thrombin­antithrombin complex(TAT)와 plasmin­α₂­plasmin inhibitor complex(PIC)를 측정하여 비교하고, 당뇨병 환자에서 미세혈관 합병증과 대혈관합병증의 유무에 따른 차이와, 이미 혈관 질환의 위험인자로 알려져 있는 인자들간의 상관성을 알아보고자 하였다. 결과:1. 환자의 분포를 살펴보면 혈관합병증이 있는 군은 85명, 혈관합병증이 없는 군은 16명이었고, 평균연령은 각각 57.9±14.1세, 49.9±16.6세로 혈관 합병증이 있는 군에서 더 나이가 많았고, 체질량지수는 23.2±3.4㎏/㎡, 24.1±3.4㎏/㎡로 두 군간 유의한 차이는 없었다. 또 두 군간의 혈압 및 HbA1c, 공복혈당 및 인슐린과 C­peptide, 총 콜레스테롤, 중성지방, HDL­콜레스테롤, Lp⒜는 유의한 차이가 없었고, 미세혈관합병증이 있는 군에서 당뇨병의 유병기간이 길었다. 2. TAT 및 PIC의 농도는 정상 대조군에서는 2.8±1.2 ng/mL, 240.4±69.7 ng/mL이었고, 당뇨병 환자군에서는 9.5±22.6 ng/mL, 472.2±258.7 ng/mL이었다. TAT와 PIC 모두 당뇨병 환자군에서 정상 대조군에 비해 유의하게 증가되어 있었고(p<0.001), TAT/PIC ratio는 두 군간 차이가 없었다. 3. 당뇨병 환자의 혈관합병증에 따른 TAT 및 PIC, fibrinogen 농도는 합병증이 없는 군은 각각 4.1±2.4ng/mL, 362.2±272.0ng/mL, 322.7±102.4mg/mL으로 PIC와 fibrinogen의 증가를 보였으나, 연령을 보정한 후에는 통계학적 유의성은 없었다. 또 대혈관 합병증군에서는 각각 6.0±4.9 ng/mL, 507.4±321.6 ng/mL, 427.1±194.7 mg/dL이었으며 미세·대혈관 합병증군에서는 10.4±6.4 ng/mL, 484.8±269.7 ng/mL, 388.4±132.4 mg/dL으로 TAT의 증가를 보였으나 역시 연령을 보정한 후에는 통계학적 유의성은 없었다. 4. 미세혈관합병증군에서 HbA1c(>8%)가 높은 군의 PIC 농도가 유의하게 높았고(p=0.049), 대혈관합병증군에서 HbA1c(>8%)가 높은 군의 총 콜레스테롤 농도가 유의하게 높았다(p=0.042). 5. 총 당뇨병 환자군에서 PIC는 fibrinogen과 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며(r=0.47, 0.31,-0.25), 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다(r=0.67). 결론:이상의 결과에서 혈장 TAT 및 PIC 농도는 당뇨병 환자에서 정상 대조군에 비해 의미있게 증가되어 있었고, 당뇨병 환자군에서는 연령의 증가와 유병기간이 혈액응고항진 및 용해의 장애에 큰 역할을 함을 알 수 있었으며, 총 당뇨병 환자군에 PIC와 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다. 따라서 당뇨병 환자에서 혈액응고 및 용해의 장애가 동반되어 있다고 볼 수 있으며, 혈장 TAT 및 PIC는 혈관합병증으로의 진행을 예측하는 지표로서 유용하리라 생각된다. 또 혈당조절정도와 상관성이 있으므로 혈당조절후에 추적검사를 시행하여 합병증의 예방이 가능한지 추후 연구가 필요하리라 생각된다. Background : Abnormality of coagulation and fibrinolystic system is known as a predisposing factor of vascular complication in diabetes. Although the pathogenesis is not well known, non-enzymatic glycation reaction and the increase in production of free radicals due to an increased oxidative stress may be linked to the hypercoagulibility and hypofibrinolytic activity. As indices of abnormality in coagulation and firinolysis in peripheral blood, plasma thrombin-antithrombin Ⅲ complex (TAT) and plasmin-α_2-plasmin inhibitor complex (PIC) were measured. The purpose of this study was to clarify whether hypercoagulability exists in diabetic patients with or without vascular complication. Methods : In our study, we measured plasma thrombin-antithrombin Ⅲ compelx (TAT) and plasmin-α_2-plasmin inhibit or complex (PIC) in 101 diabetic subjects and 20 controls. Comparing TAT and PIC levels in diabetic microvascular complication group, diabetic macrovascular complication group and controls, we examined correlation between risk factors associated with diabetic vascular complication. Results : 1. The group with diabetic vascular complication was older than group without complication. There was no significant difference in BMI, blood pressure, HbA_ic, blood sugar level, insulin, C-peptide, serum creatinine, total cholesterol, triglyceride, HDL-cholesterol, Lp (a) between two groups. The group with diabetic microvascular complication had longer duration of diabetes. 2. Concentration of TAT and PIC were 2.8±1.2 ng/ mL, 240.4±69.7 ng/ mL in controls and 9.5±22.6 ng/ mL, 472.2±258.7 ng/ mL in diabetic patients, respectively. TAT and PIC were significantly higher in diabetic patients than in control (p<0.001). But TAT/PIC ratio was no significant difference between two groups. 3. In diabetic patients, concentration of TAT and PIC and fibrinogen were respectively 4.1±2.4 ng/ mL, 362.2±272.0 ng/ mL, 322.7±102.4 mg/ dL in group without vascular complication and 5.3±4.1 ng/ mL, 529.5±258.7 ng/ mL, 374.9±106.2 mg/ dL in group with microvascular complication, which group had increase in PIC and Fibrinogen but no significance after correction of age. Concentration of TAT and PIC and Fibrinogen were 60.±4.9 ng/ mL, 507.4±321.6 ng/ mL, 427.1±194.7 mg/ dL in macrovascular complication, and 10.4±6.7 mg/ mL, 484.8±269.7 ng/ mL, 388.4±132.4 mg/ dL in combined vascular complication which group showed increase of TAT but also had no significant increase after correction of age. 4. In diabetic microvascular complication patients, group of high HbA_1c (>8%) (p=0.049) had significant high PIC concentration. In diabetic macrovascular complication patients, group of high HbA_1c (>8%) (p=0.042) had significant high total cholesterol concentration. 5. In all diabetic patients, PIC was positively correlated with fibrinogen and HbA_1c and negatively correlated BMI (r=0.47, 0.31, -0.25). Only in daibetic patients without angiopathy, TAT was positively correlated with HbA_1c (r=0.67). Conclusion : In this study, plasma TAT and PIC concentration significantly increased in diabetic patients compared with controls, and PIC was increased in group with microvascular complication, TAT were increased in group with combined micro macrovascular complication. However, there was no significance relationship existed when correctinf for age. PIC was correlated with HbA_1c. TAT was correlated with HbA_1c only in the group without angiopathy. Abnormality of coagulation and fibrinolysis were combined in diabetes, plasma TAT and PIC can be used as an index of vascular complication. Also we found the correlation with the degree of the blood glucose control. Therefore we need follow up study for the possibility of prevention of vascular complication after controlling the blood glucose to age-matched patients (J Kor Diaabetes Asso 25:354~363, 2001).

야쿠트어 폐쇄자음 연구-러시아어 차용어휘 분석-

강덕수 ( Duck Soo Kang ),김지선 ( Jee Sun Kim ),홍준희 ( Jun Hee Hong ) 한국외국어대학교 언어연구소 2007 언어와 언어학 Vol.0 No.39

Duck-soo Kang.Jee-sun Kim.Jun-hee Hong. 2007. A Study of Obstruents in Yakut through Analysis of Borrowed Words from Russian. Language and Linguistics 39, 1-16. One of the most important constraints in Yakut is connected with syllabic structure. Its syllabic structure is based on CV. So the constraint of "NoGeminates" is strictly applied. And the harmony between features is also considered important. Yakut has the strict constraint on the phonotactical relations. In Yakut a feature [constricted glottis] works more vigorously than [voiced]. This feature is combined with a feature [+back] or [+lab], making new constraints on the initial place: *#[+back, -CG], *# [+lab,+CG]. Finally, consonantal assimilation in obstruents of Yakut is dominated by 2 lows of constraints. VowelHarmony >> Ident-CV[pl] >> NCP >> *[+palatal]# >> Ident-IO; *#[+back, -cont][+back,-high] >> *#[+back,-CG], *# [+lab,+CG] >> [+cont] >> NoGem >> Ident-IO >> *[+voiced]#

達川水系의 水質管理를 위한 水理모델링

金知學,張仁洙 忠州大學校 1993 한국교통대학교 논문집 Vol.28 No.-

This study aims at the provision of the necessary information for river water quality management. QUAL2-E model was selected as water quality management madel. HEC-2 model, which utilize the standard step method was applied for the estimation of hydraulic coefficients of the model. It was applied to the stream sections in Dalchun river system.

Digital Imaging Fiber-Optic Trans-Illumination과 Confocal Laser Scanning Microscope를 이용한 초기 법랑질 우식증 연구

김종수,김지태,김성오 大韓小兒齒科學會 2006 大韓小兒齒科學會誌 Vol.33 No.1

최근 새로 개발된 DIFOTI(Digital Imaging Fiber-Optic Transillumination) 시스템의 초기 법랑질 우식증 진단 능력을 평가하고 임상 적용의 가능성을 타진해 보고자 본 연구를 시행하였다. 임상 연구는 유치 탈락 시기에 근접한 학령기 아동 23명을 대상으로 DIFOTI 이미지 촬영을 시행하고 자연 탈락된 유치 20개를 수거하여 CLSM 촬영 결과를 바탕으로 민감도(sensitivity)와 특이도(specificity)를 산출하였으며, 실험실 연구에서는 수거된 40개의 유치를 대상으로 Carbopol 인공 우식 용액으로 1,2,4 그리고 8일간 탈회시킨 후 각각 방사선 사진, DI-FOTI 이미지 그리고 CLSM와 비교 분석하여 다음과 같은 결론을 얻었다. 1. 구내에서 촬영한 DIFOTI 이미지의 민감도는 0.61이었고, 특이도는 0.63이었다. 2. 실험실에서 인공 탈회시킨 유치의 협설면 초기 우식증에 대한 DIFOTI 이미지의 민감도는 0.71 였고, 특이도는 0.75였다. The purpose of this study were to evaluate the efficacy of the newly developed Digital Imaging Fiber-Optic Trans-Illumination(DIFOTI) system in detecting carious lesions in in vivo as gold standard with confocal laser scanning microscopy and compared the efficacy of traditional radiography and DIFOTI system in in vitro as gold standard with confocal laser scanning microscopy, too. For the in vivo study, the subject pool consisted of 23 grammar school age patients just prior to entering the mixed dentition phase. Each patient was given a DIFOTI examination of the anterior and posterior teeth. During 6~8 months. the naturally expire primary teeth were collected and the efficacy of DIFOTI system was compared with confocal laser scanning microscopy. For in vitro study, 40 primary teeth were collected and decalcified by Carbopol decalcification solution for 1,2,4 and 8 days. Every experiment period. all teeth were DIFOTI examined and sectioned to take an image of confocal laser scanning microscopy. Sensitivity and specificity were calculated from the result of DIFOTI examine and confocal laser scanning microscopy analysis. The results and as follows: 1. From the in vivo study, the sensitivity of DIFOTI examine was 0.61 and specificity was 0.63. 2. From the in vitro study, the sensitivity of DIFOTI examine was 0.71 and specificity was 0.75.

대장통과시간 측정용 방사선 비투과성 표지자인 KolomarkTM의 국내 개발

김지은,이풍렬,김영호,성인경,심상군,김재준,고광철,최규완,임효근,서수원 대한소화관운동학회 1999 Journal of Neurogastroenterology and Motility (JNM Vol.5 No.2

高層아파트 主立面 디자인에 관한 硏究 : 視知覺的 측면을 중심으로

金正在,李光永,姜智秀 경북대학교 산업기술연구소 1991 産業技術硏究誌 Vol.19 No.-

The aim of this study is to search for correlation of visual experience with the design elements of main facade in high-rise apartment house and their formal characteristics. The main interest is to know how visual experience changes in accordance with the variation of formal characteristics and which formal characteristics have great influence on visual experience in high-rise apartment house.

오이(Cucumis sativus L.) 떡잎의 노쇠화 관련 유전자의 발현 특성과 그 유전자에 미치는 자스몬산의 영향에 관한 연구

한지수, 김대재 충북대학교 과학교육연구소 2011 과학교육연구논총 Vol.27 No.1

본문 참고

용수공급용 저수지의 월유입량 추정

金知學,許彰桓,張仁洙 충주대학교 1997 한국교통대학교 논문집 Vol.32 No.2

This study focused on estimating the monthly inflows for impounding reservior. Data used in the monthly estimated inflows calculation were the monthly rainfalls and the monthly observed inflows of the Sayeon dam with the record length from 1986 to 1995 in Taewha river basin. For the model verification, the values of Model Efficiency(ME), Root Mean Square Error (RMSE),Bias,Volume error (VER) and Correlation Coefficient(R)were calculated to the observed and the estimated inflows. As a result, Tank model was superior to Kajiyama model in accuracy, and the monthly estimated inflows by Tank model could be used to the various water resources planning