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)

Bleomycin이 Mouse신사구체 및 근위요세관 상피세포의 미세구조에 미치는 영향

김진택,황세진,정호삼,이규식 한양대학교 의과대학 1988 한양의대 학술지 Vol.8 No.2

Bleomycin, a glycopeptide antibiotic isolated from Streptomyces Verticillus, has been used as an anticancer drug active against human squamous cell carcinoma of skin and lung. It is well known that bleomycin inhibits DNA synthesis of tumor cell by scissoring DNA molecule and inhibiting DNA polymerase activity. Although bleomycin is very effective on various human cancers, it may damage certain normal cells to cause pulmonary and skin toxicity. In this experiment, the author pursued the effect of bleomycin on the mouse kidney, observing the ultrastructural changes in the proximal convoluted tubular epithelial cells and glomeruli. Healthy male mice(ICR strain) were used as experimental animals which were divided into two groups, the control and bleomycin treated groups. The bleomycin treated groups were subdivided into group of 3 times successive bleomycin treated and group of 7 times successive bleomycin treated. All experimental animals were given food and water ad libitum. The animals of bleomycin treated group were administered bleomycin 3 times and 7 times respectively, in a dose of 20 units per kg of body weight with 3 days interval. The experimental animals were sacrified in 24 hours after final administration of bleomycin. The specimens obtained from cortical region of left kidney were stained with uranyl acetate and lead citrate by the double contrast method and were observed with JEM 100cx-Ⅱ electron microscope. The results obtained were as follows: 1. In the epithelial cells of the proximal tubule the pinocytic vesicles were increased in number and also numerous autophagic vacuoles and the multivesicular bodies were found. 2. The deformed mitochondria and the dilated cisternae of rough endoplasmic reticulum were appeared in the epithelial cells of proximal renal tubule. 3. The basal infoldings were dilated and basement membrane were thickened and irregulary arranged at the basal portion of the epithelial cells of proximal tubule. 4. In the glomeruli the lamine densa of filterating membrane were irregulary arranged and thickened and many of the pedicles of podocytes were fusal together. It is consequently suggested that bleomycin damages both proximal convoluted tubular epithelial cells and glomeruli in mice kidney.

디지털 측방두부규격방사선사진과 MDCT의 3차원 재구성 영상을 이용한 합성측방두부규격방사선사진의 계측치 비교 및 머리 위치가 미치는 효과

김미자,최보람,허경회,이원진,허민석,이삼선,최순철 대한구강악안면방사선학회 2009 Imaging Science in Dentistry Vol.39 No.3

Purpose : To investigate the reproducibilities and compare the measurements in digital and MDCT-synthesized cephalometric radiograph, and to investigate the effect of head position on the measurement during imaging with MDCT. Materials and Methods : Twenty-two dry skulls (combined with mandible) were used in this study. Conventional digital cephalometric radiograph was taken in standard position, and MDCT was taken in standard position and two rotated position (10°left rotation and 10°right tilting). MDCT data were imported in OnDemand?? and lateral cephalometric radiograph were synthesized from 3D virtual models. Two types of rotated MDCT data were synthesized with default mode and with corrected mode using both ear rods. For all six images, sixteen angular and eleven linear measurements were made in V-Ceph?? three times. Reproducibility of measurements was assessed using repeated measures ANOVA and ICC. Linear and angular measurements were compared between digital and five MDCTsynthesized images by Student t-test. Results : All measurements in six types of cephalometric radiograph were not statistically different under ICC examination. Measurements were not different between digital and MDCT-synthesized images (P> .05). Measurements in MDCT-synthesized image in 10°left rotation or 10°right tilting position showed possibility of difference from digital image in some measurements, and possibility of improvement via realignment of head position using both ear rods. Conclusion : MDCT-synthesized cephalometric radiograph can substitute conventional cephalometric radiograph. The error on head position during imaging with MDCT have possibility that can produce measurement errors with MDCT-synthesized image, and these position error can be corrected by realignment of the head position using both ear rods. (Korean J Oral Maxillofac Radiol 2009; 39 : 133-47)

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.

舞踊의 社會化 過程 硏究

김삼진,오율자 漢陽大學校 體育科學硏究所 1994 體育科學 Vol.14 No.14

We should maintain firmly our stance in order to cope with any prejudice or any belief in terms of the process of dance socialization. At a time, in the field of sports sociology, it has majorly been projected in the sphere of learning of social science for a needed methodology for the subject sol- ution and not been established a characteristic knowledge and methodological sys- tem by accepting with almost non-criticism, therefore, the process of dance socialization should be emphasized on this, and making firmness a position of one of the part as a individual sphere of learning among the sports sociology, and then it, in its own way, should be needed to develops with deepest concerns to which we study a various variable factors with proper methodology on what shall we do a objective of study and of interesting relations on the process of dance socializtion of dancer together with a broaden understanding over the pre-existing sports sociology in order to build a creative and systematic knowledge system. The people who are living in mordern society can't overlook the society, there-fore we should enhance many things such as social nature, cooperation, esthetic sense, imaginative power and emotion by means of direct participation(a work of performance and a class) and indirect participation(viewing of artistic work, the affiliation of an aid association) which can be achieved through dance. It is very essential for goverment to devise and develop nationwide dancing program. When· it comes to our proposal for the future researcher, we should come up with well-planned research blueprint.

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.

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

방사선사진에서의 골질과 임상적으로 평가한 골질 분류의 상관관계

김현우,허경회,박관수,김정화,이원진,허민석,이삼선,최순철 대한구강악안면방사선학회 2006 Imaging Science in Dentistry Vol.37 No.1

Purpose : To investigate the validity of digital image processing on panoramic radiographs in estimating bone quality before endosseous dental implant installation by correlating bone quality in radiographic images with clinical bone quality classification. Materials and Methods : An experienced surgeon assessed and classified bone quality for implant sites with tactile sensation at the time of implant placement. Including fractal dimension eighteen morphologic features of trabecular pattern were examined in each anatomical sites on panoramic radiographs. Finally bone quality of 67 implant sites were evaluated in 42 patients. Results : Pearson correlation analysis showed that three morphologic parameters had weak linear negative correlation with clinical bone quality classification showing correlation coefficients of -0.276, -0.280, and -0.289, respectively (p<0.05). And other three morphologic parameters had obvious linear negative correlation with clinical bone quality classification showing correlation coefficients of -0.346, -0.488, and -0.343 respectively (p<0.05). Fractal dimension also had a linear correlation with clinical bone quality classification with correlation coefficients -0.506 significantly (p<0.05). Conclusion : This study suggests that fractal and morphometric analysis using digital panoramic radiographs can be used to evaluate bone quality for implant recipient sites. (Korean J Oral Maxillofac Radiol 2006; 36 : 25-32)