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      • 악성 흉막삼출액에서 Bleomycin을 이용한 흉막유착설의 시술효과

        박정현,김학렬,양세훈,정은택 圓光大學校 醫科學硏究所 2002 圓光醫科學 Vol.17 No.1

        목적: 악성 흉막삼출액이 반복적이고 지속적으로 발생하는 경우, 호흡곤란, 흉통등의 증상을 유발시키므로 흉막경화제에 의한 흉막유착술을 시행할 수 있다. 흔히 사용되던 talc의 심각한 부작용이 보고되고 있고, doxycycline 주사제도 국내에서 발매되지 않고 있다. 이에 연자들은 항암제로 소개된 bleomycin을 이용한 흉막유착술의 단기와 중기효과, 부작용 및 생존율 등을 전향적으로 확인하였다. 방법: 2000년 1월부터 2001년 12열까지 원광대학교 부속병원에 내원하여 반복적이고 지속적인 악성 흉막삼출액으로 흉막유착술이 필요한 26명의 환자를 대상으로 특별한 전 처치 없이 bleomycin 60 unit를 식염수와 함께 흉강 내 주입 후, 1일 후의 흉관에 의한 배액량을 확인하고 부작용을 관찰하였으며, 1개월 후에 흉부 방사선상으로 재 저류 유무를 확인하였다. 또한 시술 반응군과 비반응군으로 나누어 중앙생존기간을 비교분석 하였다. 결과: 시술 1일 후 26예중 10예(38%)에서 배액이 없었고, 8예(31%)에서 배액량이 100ml이하였으며, 8예(31%)는 100ml이상이었으나 시술 전보다 감소하였으며 증가된 경우는 없었다. 유의할만한 부작용은 4예(고열 3예, 흉통 1예)에서 발생하였으나, 대증요업으로 조절되었다. 시술 1개월 후 흉부 방사선과 26예중 9예(35%)는 재 저류액이 없었고, 10예(38%)는 저류액이 있으나 시술 전보다 감소하였으며, 1예(4%)는 이전과 변화가 없었고, 6예(23%)는 시술 전보다 저류액이 증가하였다. 시술 후 단기 및 중기효과를 반응군과 비반응군으로 나누어 중앙생존기간으로 양군간을 비교하였을 때, 반응군에서 연장이 되었으나 통계적으로 유의한 차이는 없었다. 결론: 이상의 결과로서 bleomycin에 의한 흉막유착술은 다른 경화제보다 특별한 전 처치가 필요 없는 간편하고, 비교적 부작용이 적은 안전한 방법이며, 효과적인 치료성적을 보이는 시술로 사료된다. Background : Malignant pleural effusions are common and significant problems in patients with advanced malignancy. Repeated thoracentesis provides temporary symptomatic improvement, but most patients progressively cause dyspnea or pleuritic pain. So pleurodesis with sclerosing agent is effective as a palliative treatment. There are many drugs used as pleural sclerosing agents. But doxycycline hasn't been used in Korea since 1999. And recently talc has been reported serious side effects. In this study, pleurodesis with bleomycin was prospectively investigated for its short term and middle period effects and its side effects. Methods : Twenty-six patients with malignant pleural effusion were prospectively analyzed to estimate the effects of bleomycin pleurodesis. Without special management before the procedure, 60 units of bleomycin in 50-100ml of normal saline were instilled into the pleural space via a small bore catheter(8-10 F). Andthen repeated positional changes and rotations were done for 2 hours. We measured the drainage amount and evaluated the side effects after 24 hours and checked the existence of the effusion by chest radiography after 1 month. Results : After 24 hours, the drainage amount showed that the responder group(none or ≤ 100ml) was 69%, and that the nonresponder group(> 100ml) was 31%. Side effects (high fever in 3 cases and severe pleuritic pain in 1 case) were 15%(4/26), but patients recovered easily by symptomatic management. After 1 month, chest radiography showed that the response rate(complete or partial response) was 73%. Differences of survival times between responder and nonresponder group was not statistically significant. Conclusions : We are suggest that bleomycin as a pleural sclerosing agent is a relatively simple, safe and effective agent. But a prospective study with a larger number of patients must be warranted.

      • 한국산 가시톡토기과의 분류학적 검토

        이병훈,이원구,김학렬 全北大學校 生物學硏究所 1984 生物學硏究年報 Vol.5 No.-

        A preliminary test concerning variabilities of some Tomoceridae species of collembola has been made using scanning electron microscopy and enzyme analysis. No definite taxono mical characters were detected in the integument of 6 species belonging 2 subgenera of Tomocerus genus. The zymograms obtained by electrophoresis, however, revealed that th subgeneric characters at times should be questioned for its monophyletic meaning as suggested by those of Tomocerus (Tomocerus) kinoshitai showing a particular pattern and Tomocerus (Tomocerina) liliputanus for its apprectable variability. The distinctive zymograms of T.laxalamella might also justify the creation of a new subgenus when considered in combination with the morphological characteristics of mucron. Neither population nor interspecific difference were observed, however, in and between T. cuspidatus and T. ocreatus, which would remain problematic and necessitate further works to confirm. Tomocerus laxalamella and T. liliputanus showed more of less variabilites whereas Homidia koreana of Entomobryidae, used as out-group for comparison, displayed a prominent individual variations in a few loci.

      • SCIESCOPUS

        Programmed death ligand-1 expression and its prognostic role in esophageal squamous cell carcinoma

        Kim, Ryul,Keam, Bhumsuk,Kwon, Dohee,Ock, Chan-Young,Kim, Miso,Kim, Tae Min,Kim, Hak Jae,Jeon, Yoon Kyung,Park, In Kyu,Kang, Chang Hyun,Kim, Dong-Wan,Kim, Young Tae,Heo, Dae Seog Baishideng Publishing Group Inc 2016 WORLD JOURNAL OF GASTROENTEROLOGY Vol.22 No.37

        <P><B>AIM</B></P><P>To investigate the expression and prognostic role of programmed death ligand-1 (PD-L1) in locally advanced esophageal squamous cell carcinoma (ESCC).</P><P><B>METHODS</B></P><P>A total of 200 patients with ESCC who underwent radical esophagectomy with standard lymphadenectomy as the initial definitive treatment in Seoul National University Hospital from December 2000 to April 2013 were eligible for this analysis. Tissue microarrays were constructed by collecting tissue cores from surgical specimens, and immunostained with antibodies directed against PD-L1, p16, and c-Met. Medical records were reviewed retrospectively to assess clinical outcomes. Patients were divided into two groups by PD-L1 status, and significant differences in clinicopathologic characteristics between the two groups were assessed.</P><P><B>RESULTS</B></P><P>Tumor tissues from 67 ESCC patients (33.5%) were PD-L1-positive. Positive p16 expression was observed in 21 specimens (10.5%). The H-score for c-Met expression was ≥ 50 in 42 specimens (21.0%). Although PD-L1-positivity was not significantly correlated with any clinical characteristics including age, sex, smoking/alcoholic history, stage, or differentiation, H-scores for c-Met expression were significantly associated with PD-L1-positivity (OR = 2.34, 95%CI: 1.16-4.72, <I>P</I> = 0.017). PD-L1 expression was not significantly associated with a change in overall survival (<I>P</I> = 0.656). In contrast, the locoregional relapse rate tended to increase (<I>P</I> = 0.134), and the distant metastasis rate was significantly increased (HR = 1.72, 95%CI: 1.01-2.79, <I>P</I> = 0.028) in patients with PD-L1-positive ESCC compared to those with PD-L1-negative ESCC.</P><P><B>CONCLUSION</B></P><P>PD-L1 expression is positively correlated with c-Met expression in ESCC. PD-L1 may play a critical role in distant failure and progression of ESCC.</P>

      • SCIESCOPUSKCI등재

        Insect Cell Culture for Recombinant β-galactosidase Production Using a Spin-filter Bioreactor

        Kim, Hak Ryul,Lee, Ki Woong,Kim, Tae Yong,Oh, Jai Hyun,Yang, Jai Myung,Kang, Seok Kwon,Chung, In Sik 한국미생물 · 생명공학회 1994 Journal of microbiology and biotechnology Vol.4 No.3

        Spodoptera frugiperda IPLB-SF-21-AE cells were cultivated in a spin-filter bioreactor with continuous perfusion for the recombinant β-galactosidase production. At the perfusion rate of 0.06 hr^-1, the maximum cell density of insect cells in this bioreactor system reached 3.5×10 exp (6) viable cells/㎖ using the Grace media containing 5% FBS and 0.3% Pluronic F-68. The recombinant β-galactosidase production of 8,100 units per reactor volume was also achieved at this perfusion rate.

      • SCIESCOPUSKCI등재

        Regulation of NAD+-Specific Isocitrate Dehydrogenase from Pythium ultimum

        Kim, Hak Ryul,Weete, John D. 생화학분자생물학회 2000 BMB Reports Vol.32 No.4

        The NAD^+-specific activity of a dual coenzyme-specific isocitrate dehydrogenase (IDH; EC 1.1.1.41) from the primitive fungus Pythium ultimum was investigated to elucidate the regulatory factors that may influence the intracellular distribution of carbon and the availability of intermediates, e.g. citrate, for fatty acid synthesis. Inhibition of NAD^+-IDH activity by diphospho- and triphosphonucleotides (ATP, ADP, and GTP) reflected the sensitivity of this enzyme to cellular energy charge even though monophosphonucleotides (AMP and GMP) had little effect on activity. NADPH, but not NADH, substantially inhibited NAD^+-IDH activity, showing noncompetitive inhibition with isocitrate. Oxalacetate and α-ketoglutarate showed competitive inhibition with isocitrate, while citrate and cis-aconitate showed mixed-noncompetitive inhibition with isocitrate. Inhibition by these substances ranged from 29 to 46% at 10 mM. The inhibitory effect of oxalacetate was increased synergistically by glyoxylate, which alone caused 31% uncompetitive inhibition at 10 mM, and a mixture of the two substances at 1 mM each showed 98% inhibition of NAD^+-IDH activity. The regulation of NAD^+-IDH in Pythium ultimum seems to be a complex process involving mitochondrial metabolites. The addition of glyoxylate (3 mM) and oxalacetate (3 mM) to the culture medium resulted in the production of 49% more lipid by P. ultimum.

      • Free Paper Presentation : OS-66 ; Down-Regulated SIRT1 by Non-Steroidal Anti-Inflammatory Drugs Is to Inhibit TGF-β1-Induced Epithelial-Mesenchymal Transition and to Suppress Migration and Invasion in Lung Cancer

        ( Hak Ryul Kim ),( Ki Eun Hwang ),( Eun Taik Jeong ) 대한결핵 및 호흡기학회 2014 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.118 No.-

        Background: Non-steroidal anti-inflammatory drugs (NSAIDs) has been reported to suppress lung cancer invasion and metastasis. However, the mechanism in lung cancer epithelial-mesenchymal transition (EMT) by NSAIDs is not clearly known. The class III deacetylase sirtuin 1 (SIRT1) possesses both pro- and anticarcinogenic properties. In this study, we investigated the role of NSAIDs as an inhibitor of TGF-β1-induced EMT, and the underlying mechanisms of suppressing lung cancer migration and invasion by celexib and sulindac. Methods: We evaluated the efficacy of celecoxib and sulindac in TGF-β1-induced EMT. EMT-related molecular alterations were detected by western blotting. Electric cell-substrate impedance sensing (ECIS) was used to evaluate the migration and invasion of A549 cells. The matrix metalloproteinase (MMP) gelatinolytic activity was determined by gelatin zymography, and protein expression was measured by western blotting. In addition, SIRT1 was knocked down or overexpressed to determine its role in preventing TGF-β1-induced EMT by celecoxib or sulindac. Results: Celecoxib was more effective in preventing TGF-β1-induced EMT, as compared with sulindac treatment, indicating upregulation of the epithelial marker, E-cadherin, and downregulation of N-cadherin, mesenchymal and transcription factors. Moreover, ECIS assay showed that celecoxib and sulindac could inhibit TGF-β1-enhanced migration and invasion of A549 cells. Increment in MMP-9 expression compared to that of MMP-2 following activation of TGF-β1 was also observed. However, treatment with celecoxib or sulindac inhibited MMP-9 expression. SIRT1 downregulation enhanced reverse of TGF- β1-induced EMT by celecoxib or sulindac. In contrast, SIRT1 upregulation had a relevant role in TGF-β1-induced EMT. Conclusions: Celecoxib and sulindac can inhibit TGF-β1-induced EMT and suppress lung cancer migration and invasion via down-regulation of SIRT-1. SIRT1 is positive regulator of TGF-β1-induced EMT and potential therapeutic target to reverse EMT and to prevent lung cancer progression.

      • The Changes of Ecdysteroid titre during Moulting and Ovary Maturation of Bombyx mori L.

        Kim, Hak-Ryul,Yu, Jeong-Heui 한국곤충학회 1984 Korean journal of entomology Vol.14 No.2

        누에의 탈피 및 란성숙 조절에 관여하는 호르몬인 ecdysteroid 농도와 terminal oocyte의 성숙과정을 H.P.L.C.와 광학현미경을 이용하여 비교 관찰하였다. 1. 암컷 whole body의 ecdysteroid 농도는 4령 유충에서는 3일 그리고 종령유충은 4일과 8일에 각각 peak를 보여 주었다. 2. 용시기 및 우화직후에 걸쳐서 암컷은 용화후 5일과 9일에 두개의 peak를 나타내 반면 수컷은 1일에 하나의 peak를 보여주었다. 3. 란집내의 ecdysteroid 농도는 용화후 9일에 peak를 나타내었다. 4. Terminal of oocyte의 크기는 용화후 5일에 증가하여 7일에 최내에 달하며 그 이후는 동일한 크기를 보여 주고 있는데, 5일에 란황형성이 이루어지고 있고 7일에는 영양세포가 퇴화되었다. The changes of ecdysteroid titre during moulting and ovary maturation, and the maturation of the terminal oocyte were investigated by H.P.L.C. and Light microsopy 1. During the 4th, 5th instar larval and prepupal stage ecdysteroid peaks of female whole body show the 3rd day at the 4th instar stage and 4-th and 8th day respectively at 5th instar stage. 2. During the pupal stage female represents two peaks on 5th and 9th day respectively whereas male shows the peak on 1st day. 3. Ecdysteroid concentration of ovary reaches the peak on 9th day. 4. On 5th day after pupation, nurse cells are pre-sent and yolks are formed but on 7th day vitelline membrane was already formed and on 9th day maturing oocyte appears.

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