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      • Diagnostic usefulness of a T cell-based assay for latent tuberculosis infection in kidney transplant candidates before transplantation

        Kim, S.-H.,Lee, S.-O.,Park, I.-A.,Park, S.J.,Choi, S.-H.,Kim, Y.S.,Woo, J.H.,Park, S.-K.,Park, J.S.,Kim, S.C.,Han, D.J. Blackwell Publishing Inc 2010 Transplant infectious disease Vol.12 No.2

        <P>S.-H. Kim, S.-O. Lee, I.-A. Park, S.J. Park, S.-H. Choi, Y.S. Kim, J.H. Woo, S.-K. Park, J.S. Park, S.C. Kim, D.J. Han. Diagnostic usefulness of a T cell-based assay for latent tuberculosis infection in kidney transplant candidates before transplantation.Transpl Infect Dis 2010: <B>12:</B> 113–119. All rights reserved</P><P>Background</P><P>The presence of latent tuberculosis (TB) infection (LTBI) should be evaluated before kidney transplantation. Although a new T cell-based assay for diagnosing LTBI gave promising results, this assay has not yet been compared with the tuberculin skin test (TST) for diagnosing LTBI in renal transplant candidates before transplantation.</P><P>Patients and methods</P><P>All adult patients admitted to a single institute for renal transplantation over a 1-year period were prospectively enrolled. A clinically predictive risk of LTBI was defined as: (i) recent close contact with a person with pulmonary TB; (ii) abnormal chest radiography; (iii) a history of untreated or inadequately treated TB; or (iv) a new infection (i.e., a recent conversion of TST).</P><P>Results</P><P>Of 209 renal recipients, 47 (22%) had a positive TST≥5 mm, 21 (10%) had a positive TST≥10 mm, 65 (30%) had a positive T-SPOT.<I>TB</I> test, and 25 (12%) had an indeterminate T-SPOT.<I>TB</I> test. The induration size of TST was significantly associated with a high positivity rate on T-SPOT.<I>TB</I> (<I>P</I><0.001). Agreement between T-SPOT.<I>TB</I> test and TST≥10 mm was fair (<I>k</I>=0.24, 95% confidence interval 0.11–0.36). However, neither univariate nor multivariate analysis showed any association between the clinical risk for LTBI and positivity on T-SPOT.<I>TB</I> or TST.</P><P>Conclusion</P><P>T-SPOT.<I>TB</I> test was more frequently positive than TST in renal transplant candidates. However, further longitudinal studies are awaited to determine whether the ability of T-SPOT.<I>TB</I> assay to detect LTBI in renal transplant recipients can better predict the development of TB than can TST after transplantation.</P>

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        Production of (S)-3-hydroxybutyrate by metabolically engineered Saccharomyces cerevisiae

        Yun, E.J.,Kwak, S.,Kim, S.R.,Park, Y.C.,Jin, Y.S.,Kim, K.H. Elsevier Science Publishers 2015 Journal of biotechnology Vol.209 No.-

        (S)-3-Hydroxybutyrate (S-3HB) can be used as a precursor for the synthesis of biodegradable polymers such as polyhydroxyalkanoate and stereo-specific fine chemicals such as antibiotics, pheromones, and drugs. For the production of S-3HB in yeast, the biosynthetic pathway of S-3HB from acetyl-CoA, consisting of the three enzymes, acetyl-CoA C-acetyltransferase (ACCT), acetoacetyl-CoA reductase (ACR), and 3-hydroxybutyryl-CoA thioesterase (HBT), was introduced into Saccharomyces cerevisiae. An engineered yeast strain overexpressing ERG10, hbd, and tesB genes not only exhibited enzyme activities of AACT, ACR, and HBT, but also produced S-3HB from ethanol. In order to increase the titer of S-3HB, a fed-batch fermentation based on pulse feeding of ethanol as a carbon source was performed, and a final S-3HB titer of 12.0g/L was achieved. This is the first report on the production of 3HB by engineered yeast, utilizing ethanol as the carbon source, suggesting that the industrially preferred S. cerevisiae can be a promising host for producing S-3HB.

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        <i>S100A9</i> and <i>EGFR</i> gene signatures predict disease progression in muscle invasive bladder cancer patients after chemotherapy

        Kim, W. T.,Kim, J.,Yan, C.,Jeong, P.,Choi, S. Y.,Lee, O. J.,Chae, Y. B.,Yun, S. J.,Lee, S. C.,Kim, W. J. Oxford University Press 2014 Annals of Oncology Vol.25 No.5

        <P>In our previous gene expression profile analysis, IL1B, S100A8, S100A9, and EGFR were shown to be important mediators of muscle invasive bladder cancer (MIBC) progression. The aim of the present study was to investigate the ability of these gene signatures to predict disease progression after chemotherapy in patients with locally recurrent or metastatic MIBC. Patients with locally advanced MIBC who received chemotherapy were enrolled. The expression signatures of four genes were measured and carried out further functional analysis to confirm our findings. Two of the four genes, S100A9 and EGFR, were determined to significantly influence disease progression (P = 0.023, 0.045, respectively). Based on a receiver operating characteristic curve, a cut-off value for disease progression was determined. Patients with the good-prognostic signature group had a significantly longer time to progression and cancer-specific survival time than those with the poor-prognostic signature group (P < 0.001, 0.042, respectively). In the multivariate Cox regression analysis, gene signature was the only factor that significantly influenced disease progression [hazard ratio: 4.726, confidence interval: 1.623-13.763, P = 0.004]. In immunohistochemical analysis, S100A9 and EGFR positivity were associated with disease progression after chemotherapy. Protein expression of S100A9/EGFR showed modest correlation with gene expression of S100A9/EGFR (r = 0.395, P = 0.014 and r = 0.453, P = 0.004). Our functional analysis provided the evidence demonstrating that expression of S100A9 and EGFR closely associated chemoresistance, and that inhibition of S100A9 and EGFR may sensitize bladder tumor cells to the cisplatin-based chemotherapy. The S100A9/EGFR level is a novel prognostic marker to predict the chemoresponsiveness of patients with locally recurrent or metastatic MIBC.</P>

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        20대 여성의 신발종류에 따른 족저압 영역별 비교 연구

        김용재,지진구,김정태,홍준희,이중숙,이훈식,박승범 한국운동역학회 2004 한국운동역학회지 Vol.14 No.3

        Y. J. KIM, J. G. JI, J. T. KIM, J. H. HONG, J. S. LEE, H. S. LEE, S. B. PARK. A comparison study for mask plantar pressure measures to the difference of shoes in 20 female. Korean Journal of Sport Biomechanics, Vol. 14, No. 3, pp. 83-98, 2004. The purpose of this study was to investigate the test-retest of plantar pressures using the F-Scan system over speeds and plantar regions. 6 healthy female subjects in 20's were recruited for the study. Plantar pressure measurements during locomotor activities can provide information concerning foot function, particularly if the timing and magnitude of the loading profile can be related to the location of specific foot structures such as the metatarsal heads. The Tekscan F-Scan system consists of a flexible, 0.18mm thick sole-shape having 1260 pressure sensors, the sensor insole was trimmed to fit the subjects' right. left shoes - sneakers shoes & dress shoes. It was calibrated by the known weight of the test subject standing on one foot. The Tekscan measurements show the insole pressure distribution as a function of the time. This finding has important implications for the development of plantar pressure test protocols where the function of the forefoot is important. According to the result of analysis it is as follows : 1) Center of force trajectory in women's dress shoes display direct movement, compare with center of force trajectory in Sneaker shoes displays a little bit curved slow pronation movement. Sneaker shoes in forefoot part display very quick supination movement, therefore, this shoes effects negative effectiveness for ankle's stability. Considering center of force trajectory analyzing, the more center of force close straight line, the more movement can be quick movement for locomotion. For foot pressure distribution, center of force trajectory in locomotion is better to curved trajectory with pronation movement. So sneaker shoes style is good shoes considering center of pressure distribution trajectory compare with women's dress shoes. 2) Women's dress shoes increased peak pressure in medial, this is effected by high hill's height. The more increased women's dress shoes's height, the more women's peak pressure will increase, pronation can increase compare with before. Supination movement increase, this focused pressure in lateral, also, supination increased more. If the supination movement increased, foot pressure focused in lateral, therefore, it is appeared force distribution in gait direction. This is bad movement in foot's stability. 3) Women's dress shoes in landing phase displayed a long time, this is when women's dress shoes wear, gait movement is unbalance, so, landing phase displayed a long time. For compensation in gait, swing phase quick movement. 4) Women's dress shoes displayed peak pressure distribution in lateral of rearfoot part, Sneakers shoes displayed peak pressure distribution in medial of forefoot part. Its results has good impact absorption compare with women's dress shoes. In forefoot part, sneakers shoes has good propulsive force compare with women's dress shoes.

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        Development of a system for S locus haplotyping based on the polymorphic SLL2 gene tightly linked to the locus determining self-incompatibility in radish (Raphanus sativus L.)

        Kim, D.,Jung, J.,Choi, Y. O.,Kim, S. Springer Netherlands 2016 Euphytica Vol.209 No.2

        <P>To develop a reliable system for identifying multiple S haplotypes controlling self-incompatibility (SI) in radish (Raphanus sativus L.), the genomic organization of the S locus region was identified from radish draft genome sequences. An initial attempt to find the S receptor kinase (SRK) gene, the female determinant of SI, failed due to presence of 15 homologous genes. Using synteny between the radish and Chinese cabbage genomes, the putative S locus region was identified in the radish R7 linkage group. One scaffold anchored to this R7 region contained the S-locus glycoprotein (SLG) gene, which is one of the S locus genes. Using the high homology between the SLG and S domain of SRK, the full-length radish SRK gene containing the largest 6861-bp intron1 was assembled by connecting two scaffolds harboring the S receptor and kinase domains, respectively. A scaffold containing the full-length S-locus cysteine-rich protein (SCR)/S locus protein 11 (SP11) gene, the male-determinant of SI, was identified using information reported previously. Finally, 53,785, 42,804, and 10,165 bp sequences containing the S locus genes and their flanking sequences were obtained. Unlike the various orientations of the SRK or SCR/SP11 genes, the position of SLL2 located at the border region of the S locus was conserved among haplotypes. Sequencing of the SLL2 gene from 31 inbred lines showing differential SI responses revealed 26 polymorphic alleles. Four additional SLL2 alleles were identified from analysis of diverse breeding lines. Based on the polymorphic SLL2 sequences, a new S haplotyping system was developed for efficient marker-assisted selection of the S haplotypes in radish.</P>

      • ZNF509S1 downregulates PUMA by inhibiting p53K382 acetylation and p53-DNA binding

        Jeon, B.N.,Yoon, J.H.,Han, D.,Kim, M.K.,Kim, Y.,Choi, S.H.,Song, J.,Kim, K.S.,Kim, K.,Hur, M.W. Elsevier Science 2017 Biochimica et biophysica acta. Gene regulatory mec Vol.1860 No.9

        Expression of the POK family protein ZNF509L, and -its S1 isoform, is induced by p53 upon exposure to genotoxic stress. Due to alternative splicing of the ZNF509 primary transcript, ZNF509S1 lacks the 6 zinc-fingers and C-terminus of ZNF509L, resulting in only one zinc-finger. ZNF509L and -S1 inhibit cell proliferation by activating p21/CDKN1A and RB transcription, respectively. When cells are exposed to severe DNA damage, p53 activates PUMA (p53-upregulated modulator of apoptosis) transcription. Interestingly, apoptosis due to transcriptional activation of PUMA by p53 is attenuated by ZNF509S1. Thus we investigated the molecular mechanism(s) underlying the transcriptional attenuation and anti-apoptotic effects of ZNF509S1. We show that ZNF509S1 modulation of p53 activity is important in PUMA gene transcription by modulating post-translational modification of p53 by p300. ZNF509S1 directly interacts with p53 and inhibits p300-mediated acetylation of p53 lysine K382, with deacetylation of p53 K382 leading to decreased DNA binding at the p53 response element 1 of the PUMA promoter. ZNF509S1 may play a role not only in cell cycle arrest, by activating RB expression, but also in rescuing cells from apoptotic death by repressing PUMA expression in cells exposed to severe DNA damage.

      • Integrin αvβ3-mediated transcriptional regulation of TIMP-1 in a human ovarian cancer cell line

        Kim, D.S.,Jeon, O.H.,Lee, H.D.,Yoo, K.H.,Kim, D.S. Academic Press 2008 Biochemical and biophysical research communication Vol.377 No.2

        We have previously reported that a disintegrin inhibits solid tumor growth and metastasis in mouse model [I.C. Kang, Y.D. Lee, D.S. Kim, A novel disintegrin salmosin inhibits tumor angiogenesis, Cancer Res. 59 (1999) 3754-3760; S.I. Kim, K.S. Kim, H.S. Kim, D.S. Kim, Y. Jang, K.H. Chung, Y.S. Park, Inhibitory effect of the salmosin gene transferred by cationic liposomes on the progression of B16BL6 tumors, Cancer Res. 63 (2003) 6458-462]. In this study, we have investigated the modulatory effect of a disintegrin, saxatilin, on the balance between MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in human ovarian cancer cell line MDAH 2774. Functional mechanism of the disintegrin-mediated transcriptional regulation of MMP-9 and TIMP-1 was examined in the ovarian cancer cell line. Saxatilin strongly induced TIMP-1 expression in dose- and time-dependent manners, while the disintegrin suppressed MMP-9 expression. Further analyses clearly indicated that interaction of the disintegrin and integrin αvβ3 results in the TIMP-1 promoter activation via c-fos to suppress TNF-α-induced cancer cell invasion. These results demonstrate that integrin αvβ3-mediated transcriptional regulation of MMP-9 and TIMP-1 is critical for suppressing the ovarian cancer cell invasion.

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        Inflammatory lipid sphingosine-1-phosphate upregulates C-reactive protein via C/EBPβ and potentiates breast cancer progression

        Kim, E-S,Cha, Y,Ham, M,Jung, J,Kim, S G,Hwang, S,Kleemann, R,Moon, A Macmillan Publishers Limited 2014 Oncogene Vol.33 No.27

        A crucial role of the inflammatory lipid sphingosine-1-phosphate (S1P) in breast cancer aggressiveness has been reported. Recent clinical studies have suggested that C-reactive protein (CRP) has a role in breast cancer development. However, limited information is available on the molecular basis for the expression of CRP and its functional significance in breast cell invasion. The present study aimed to elucidate the molecular link between S1P and CRP during the invasive process of breast epithelial cells. This is the first report showing that transcription of CRP was markedly activated by S1P in breast cells. Our data suggest that not only S1P treatment but also the endogenously produced S1P may upregulate CRP in breast carcinoma cells. Transcription factors CCAAT/enhancer-binding protein beta and c-fos were required for S1P-induced CRP expression. Coupling of S1P<SUB>3</SUB> to heterotrimeric G<SUB>αq</SUB> triggered the expression of CRP, utilizing signaling pathways involving reactive oxygen species (ROS), Ca<SUP>2+</SUP> and extracellular signal-related kinases (ERKs). S1P-induced CRP expression was crucial for the transcriptional activation of matrix metalloproteinase-9 through ERKs, ROS and c-fos, leading to breast cell invasion. Using a xenograft mice tumor model, we demonstrated that S1P induced CRP expression both in vitro and in vivo. Taken together, our findings have revealed a molecular basis for S1P-induced transcriptional activation of CRP and its functional significance in the acquisition of the invasive phenotype of human breast epithelial cells under inflammatory conditions. Our findings may provide useful information on the identification of useful therapeutic targets for inflammatory breast cancer.

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