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        기관지폐 이형성증의 임상 양상: 다기관 연구

        성기혜 ( Ki Hye Sung ),김민희 ( Min Hee Kim ),김은령 ( Eun Ryoung Kim ),심재원 ( Jae Won Shim ),이정주 ( Jung Ju Lee ),임재우 ( Jae Woo Im ),진현승 ( Hyun Seung Jin ) 대한주산의학회 2009 Perinatology Vol.20 No.3

        목적: 최근 극소 저출생 체중아의 생존율의 개선으로 기관지폐 이형성증(bronchopulmonary dysplasia, BPD)이 늘고 있다. 다기관 연구에 의해 전국적인 BPD의 역학, 임상 양상과 각 병원 간의 차이를 조사하여 향후 우리나라의 BPD 감소와 중증도를 줄이는 것을 목적으로 본 연구를 시행하였다. 방법: 2005년 6월부터 2007년 5월까지 건국대학교병원, 영등포 성애병원, 강북삼성병원, 중앙대학교병원, 건양대학교병원, 강릉아산병원의 신생아 집중 치료실에 입원하였던 신생아 4,476명을 대상으로 하였다. BPD의 진단 기준은 비전형적인 BPD를 포함하여 병인적인 분류를 하고 있는 Ogawa 등의 분류법을 이용하여 신생아 호흡 곤란 증후군(respiratory distress syndrome, RDS)과 전형적 또는 미만성 혼탁의 방사선 소견, 산전 감염의 유무에 따라 6가지 type으로 분류하였다. 또한 전체 신생아의 출생체중 분포와 생존율, 각 출생체중 군별 BPD의 발생률, 병태 비율, 사망률 등을 조사하고, 이 후 재택 산소요법 시행 여부와 미숙아 망막증, 괴사성 장염 등의 합병증 여부를 조사하였다. 결과: 생후 28일째 산소 치료가 필요한 신생아는 89명이었고, 이 중 Ogawa 분류법에 의한 BPD 환아는 70명(1.6%)이었으며, 특히 1,500 g 미만의 환아 237명 중 60명(25.3%)이었다. 생후 28일 이상 생존율은 98.7%이고, 사망 예는 없었으며 평균 재원 기간은 97.8±51.2일(43~405일)이었다. BPD는 900~999 g, 1,000~1,249 g의 체중 군에서 발생률이 각각 15명(21.4%)으로 가장 높았으며, 교정 36주 이후에도 산소투여가 필요한 중증 BPD의 경우 900~999 g의 체중 군에서 7명(23.3%)로 가장 높았다. Ogawa 분류법으로 BPD의 각 병태 비율로는 RDS 이후에 나타나는 I, II형이 각각 전체의 17예(24.3%), 44예(62.9%)로 대다수를 차지하였다. 이외에도 III`형은 2예(2.9%), IV형은 2예(2.9%), V형은 5예(7.1%)이었고, III형, VI형은 없었다. 재택 산소요법은 8예에서 시행되어 전체의 11.4%였으며, 이 중 BPD I형이 7예로 87.5%를 차지하였다. 미숙아 망막증은 35명(50.0%)에서 발생하였으며, 700 g 이하 신생아에서 9예(26.5%)로 가장 많았다. 또한 괴사성 장염은 3명(4.3%)이었다. 결론: 본 연구는 국내에서 처음으로 진행된 BPD의 전국적인 다기관 역학 조사로, 대상 신생아의 Ogawa 분류에 의한 BPD 유병률은 1.6% 이었고 1,500 g 미만 신생아의 25.3%이었으며, 전체 신생아의 BPD 70명 중 Ogawa 분류의 I, II형이 각각 24.3%, 62.9%로 대다수를 차지하였다. Purpose: As the neonatal intensive care advanced, the incidence of neonatal bronchopulmonary dysplasia (BPD) has increased. We conducted a multi-center investigation of the prevalence of BPD in six hospitals to investigate the epidemiology of BPD in Korea. Methods: Retrospective reviews ware performed for survival rate, prevalence of BPD of total 4,476 newborn infants who were admitted to neonatal intensive care unit in Konkuk university hospital, Sung-Ae General hospital, Kangbuk Samsung hospital, Chung-Ang university hospital, Konyang university hospital, and Gangneung Asan hospital between June, 2005 and May, 2007. By Ogawa, BPD was defined as oxygen dependency at 28 days after birth, with respiratory distress symptoms and the change of chest x-ray finding, and classified as 6 subtypes. Classic BPD was defined as oxygen dependency at 36 weeks of postmenstrual age. Results: Survival rate at 28 day after birth was 98.7%. BPD infants by Ogawa classification were 70 (1.6% of overall newborn infants), classic BPD infants were 30 (0.7%). Especially, among 237 preterm infants with birth weight less than 1,500 gram who survived to 28 days of life, 60 (25.3%) had BPD by Ogawa classification and 23 (9.7%) had classic BPD. In Ogawa classification, infants with RDS as type I and II, were 17 infants (24.3%) and 44 infants (62.9%). Home oxygen therapy was performed 8 infants (11.4%). Prevalence of retinopathy of prematurity was 35 infants (50.0%), necrotizing enterocolitis was 3 infants (4.3%), and intraventricular hemorrhage was 6 infants (8.6%). Conclusion: Prevalence of BPD infants was 1.6% of overall newborn, 25.3% of preterm infants with birth weight less than 1,500 gram. Among 70 BPD infants, BPD by Ogawa classification with history of RDS as type I and II were 24.3%, 62.9% as the majority of BPD. This study would be the first report of epidemiology of Korean BPD infants by multi-center study.

      • The Methylene Chloride Fraction of Trichosanthis Fructus Induces Apoptosis in U937 Cells through the Mitochondrial Pathway

        Lee, Eun-Ok,Lee, Ju-Ryoung,Kim, Kwan-Hyun,Baek, Nam-In,Lee, Soo-Jin,Lee, Bog-Hieu,Cho, Kyung-Dong,Ahn, Kyoo-Seok,Kim, Sung-Hoon Pharmaceutical Society of Japan 2006 BIOLOGICAL & PHARMACEUTICAL BULLETIN Vol.29 No.1

        <P><I>Trichosanthis kirilowii</I> M<SMALL>AXIM</SMALL> has been used as a folk remedy to treat diabetes, leukemia, and breast cancer. In the present study, the apoptotic mechanism of the methylene chloride fraction of Trichosanthis Fructus (MCTF) was investigated in human leukemic U937 cells. MCTF exhibited antiproliferative effectsagainst U937 cells (IC<SUB>50</SUB>=<I>ca.</I> 8 μg/ml). Apoptotic bodies were observed in MCTF-treated U937 cells in the TUNEL assay. We also confirmed that MCTF significantly increases annexin V<SUP>+</SUP>/propidium iodide-cells using FACS analysis. MCTF treatment activated caspase-8, -9 and -3, and led to cleaved poly (ADP-ribose) polymerase and release of cytochrome <I>c</I> into cytosol in a concentration-dependent manner, while MCTF did not affect Bax or Bcl-2 protein levels as shown by Western blot analysis. Taken together, these results indicate that MCTF can induce apoptosis in U937 cells chiefly <I>via</I> a mitochondrial-mediated pathway and suggest that Trichosanthis Fructus can be used in cancer treatment as a chemopreventive agent.</P>

      • Predictors of candesartan's effect on vascular reactivity in patients with coronary artery disease

        Lee, So‐,Ryoung,Chae, In‐,Ho,Kim, Hack‐,Lyoung,Kang, Do‐,Yoon,Kim, Sang,Hyun,Kim, Hyo‐,Soo BLACKWELLS 2017 CARDIOVASCULAR THERAPEUTICS Vol.35 No.5

        <P><B>Summary</B></P><P><B>Introduction and Aims</B></P><P>Endothelial dysfunction and arterial stiffness have a prognostic value on adverse long‐term outcomes in coronary artery disease (CAD) patients. We evaluated the efficacy on vascular reactivity of candesartan and analyzed predictors to control the candesartan's effect on vascular reactivity in CAD patients.</P><P><B>Method</B></P><P>Patients were prospectively enrolled and prescribed candesartan for 6 months. The effect on vascular reactivity was evaluated by the change in flow‐mediated dilation (FMD) and pulse wave velocity (PWV).</P><P><B>Results</B></P><P>A total of 124 patients completed the study. The better responder in FMD change (≥1.3%) showed significantly lower baseline FMD than the poor responder (<I>P</I> < .001). In receiver operating characteristic analysis, baseline FMD 7.5% showed optimal predictive value (sensitivity 79%, specificity 79%) for predicting better responder. The baseline endothelial dysfunction (FMD <7.5%) was the only significant predictor of the better responder to candesartan. The better responder in PWV change (≤−100 cm/s) showed greater blood pressure lowering and significantly higher baseline PWV than the poor responder (both <I>P</I> < .05). The poor responder in both FMD and PWV showed a higher prevalence of previous myocardial infarction (38.7% vs 17.2%, <I>P</I> = .013).</P><P><B>Conclusion</B></P><P>The candesartan's effect on vascular reactivity is more pronounced in patients with more severe endothelial dysfunction and arterial stiffness. Poor responders on both FMD and PWV showed higher prevalence of previous myocardial infarction.</P>

      • SCISCIESCOPUS

        Fungal Quorum Quenching: A Paradigm Shift for Energy Savings in Membrane Bioreactor (MBR) for Wastewater Treatment

        Lee, Kibaek,Lee, Seonki,Lee, Sang Hyun,Kim, Sang-Ryoung,Oh, Hyun-Suk,Park, Pyung-Kyu,Choo, Kwang-Ho,Kim, Yea-Won,Lee, Jung-Kee,Lee, Chung-Hak American Chemical Society 2016 Environmental science & technology Vol.50 No.20

        <P>In the last 30 years, the use of membrane bioreactors (MBRs) for advanced wastewater treatment and reuse have been expanded continuously, but they still suffer from excessive energy consumption resulting from the intrinsic problem of membrane biofouling. One of the major causes of biofouling in MBRs is bacterial quorum sensing (QS) via N-acylhomoserine lactones (AHLs) and/or autoinducer-2 (AI-2), enabling intra- and interspecies communications, respectively. In this study, we demonstrate that farnesol can substantially mitigate membrane biofouling in a MBR due to its quorum quenching (QQ) activity. When Candida albicans (a farnesol producing fungus) entrapping polymer beads (AEBs) were placed in the MBR, the rate of transmembrane pressure (TMP) rise-up was substantially decreased, even for lower aeration intensities. This finding corresponds to a specific aeration energy savings of approximately 40% (25% through the physical washing effect and a further 15% through the biological QQ effect of AEBs) compared to conventional MBRs without AEBs. A real-time RT-qPCR analysis revealed that farnesol secreted from C. albicans mitigated the biofilm formation in MBRs via the suppression of AI-2 QS. Successful control of biofouling and energy savings through fungal-to-bacterial QQ could be expanded to the plant scale for MBRs in wastewater treatment with economic feasibility.</P>

      • SCISCIESCOPUS

        Effective Antifouling Using Quorum-Quenching Acylase Stabilized in Magnetically-Separable Mesoporous Silica

        Lee, Byoungsoo,Yeon, Kyung-Min,Shim, Jongmin,Kim, Sang-Ryoung,Lee, Chung-Hak,Lee, Jinwoo,Kim, Jungbae American Chemical Society 2014 Biomacromolecules Vol.15 No.4

        <P>Highly effective antifouling was achieved by immobilizing and stabilizing an acylase, disrupting bacterial cell-to-cell communication, in the form of cross-linked enzymes in magnetically separable mesoporous silica. This so-called “quorum-quenching” acylase (AC) was adsorbed into spherical mesoporous silica (S-MPS) with magnetic nanoparticles (Mag-S-MPS), and further cross-linked for the preparation of nanoscale enzyme reactors of AC in Mag-S-MPS (NER-AC/Mag-S-MPS). NER-AC effectively stabilized the AC activity under rigorous shaking at 200 rpm for 1 month, while free and adsorbed AC lost more than 90% of their initial activities in the same condition within 1 and 10 days, respectively. When applied to the membrane filtration for advanced water treatment, NER-AC efficiently alleviated the biofilm maturation of <I>Pseudomonas aeruginosa</I> PAO1 on the membrane surface, thereby enhancing the filtration performance by preventing membrane fouling. Highly stable and magnetically separable NER-AC, as an effective and sustainable antifouling material, has a great potential to be used in the membrane filtration for water reclamation.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bomaf6/2014/bomaf6.2014.15.issue-4/bm401595q/production/images/medium/bm-2013-01595q_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bm401595q'>ACS Electronic Supporting Info</A></P>

      • CoMAGC: a corpus with multi-faceted annotations of gene-cancer relations

        Lee, Hee-Jin,Shim, Sang-Hyung,Song, Mi-Ryoung,Lee, Hyunju,Park, Jong C BioMed Central 2013 BMC bioinformatics Vol.14 No.-

        <P><B>Background</B></P><P>In order to access the large amount of information in biomedical literature about genes implicated in various cancers both efficiently and accurately, the aid of text mining (TM) systems is invaluable. Current TM systems do target either gene-cancer relations or biological processes involving genes and cancers, but the former type produces information not comprehensive enough to explain how a gene affects a cancer, and the latter does not provide a concise summary of gene-cancer relations.</P><P><B>Results</B></P><P>In this paper, we present a corpus for the development of TM systems that are specifically targeting gene-cancer relations but are still able to capture complex information in biomedical sentences. We describe CoMAGC, a corpus with multi-faceted annotations of gene-cancer relations. In CoMAGC, a piece of annotation is composed of four semantically orthogonal concepts that together express 1) how a gene changes, 2) how a cancer changes and 3) the causality between the gene and the cancer. The multi-faceted annotations are shown to have high inter-annotator agreement. In addition, we show that the annotations in CoMAGC allow us to infer the prospective roles of genes in cancers and to classify the genes into three classes according to the inferred roles. We encode the mapping between multi-faceted annotations and gene classes into 10 inference rules. The inference rules produce results with high accuracy as measured against human annotations. CoMAGC consists of 821 sentences on prostate, breast and ovarian cancers. Currently, we deal with changes in gene expression levels among other types of gene changes. The corpus is available at http://biopathway.org/CoMAGCunder the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0).</P><P><B>Conclusions</B></P><P>The corpus will be an important resource for the development of advanced TM systems on gene-cancer relations.</P>

      • Development and Gene Expression of Porcine Cloned Embryos Derived from Bone Marrow Stem Cells with Overexpressing Oct4 and Sox2

        Lee, Jeong-Hyeon,Lee, Won-Jae,Jeon, Ryoung-Hoon,Lee, Yeon-Mi,Jang, Si-Jung,Lee, Sung-Lim,Jeon, Byung-Geun,Ock, Sun-A,King, W. Allen,Rho, Gyu-Jin Mary Ann Liebert 2014 Cellular reprogramming Vol.16 No.6

        <P>The present study compared the potential of porcine bone marrow mesenchymal stem cells (pBMSCs) at different passages as nuclear transfer (NT) donors and the developmental efficiency of NT embryos from donor cells transfected with/without Oct4 and Sox2. Early-passage pBMSCs showed higher proliferation and expression of Oct4 and Sox2 and differentiation potential into mesenchymal lineages than middle- and late-passage pBMSCs. Cleavage rate did not differ among pBMSCs at different passages, but NT embryos with early-passage pBMSCs and middle-passage pBMSCs transfected with Oct4 (Oct4-pBMSCs) had significantly (p<0.05) higher blastocyst development than those with middle-passage pBMSCs. The incidence of apoptotic bodies in NT blastocysts from late-passage pBMSCs and Sox2-transfected middle-passage pBMSCs (Sox2-pBMSCs) was significantly (p<0.05) higher than others. The transcriptional levels of Oct4, Sox2, Nanog, Cdx2, Dnmt3a, and Igf2r genes were significantly (p<0.05) higher in Oct4- and Sox2-pBMSCs NT embryos. Middle-passage pBMSCs NT embryos revealed lower transcriptional levels of Bcl2 than others, except Sox2-pBMSCs NT embryos. The transcriptional level of Bax increased gradually in NT embryos derived from pBMSCs following extended passages and was significantly (p<0.05) higher in Sox2-pBMSCs NT embryos. Our results demonstrated that early-passage pBMSCs are more potent in expressing transcription factors and displayed higher differentiation ability, and middle-passage pBMSCs transfected with Oct4 improved the developmental efficiency of NT embryos, suggesting that high Oct4 expression cells are more efficient as NT donors.</P>

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