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        Proteomic Analysis Reveals PGAM1 Altering cis-9, trans-11 Conjugated Linoleic Acid Synthesis in Bovine Mammary Gland.

        Wang, T,Lee, S B,Hwang, J H,Lim, J N,Jung, U S,Kim, M J,Kang, H S,Choi, S H,Lee, J S,Roh, S G,Lee, H G American Oil Chemists' Society 2015 Lipids Vol.50 No.5

        <P>cis-9, trans-11 Conjugated linoleic acid (CLA) is one of the most extensively studied CLA isomers due to its multiple isomer-specific effects. However, the molecular mechanisms of cis-9,trans-11 CLA synthesis in ruminant mammary gland are still not clearly understood. This process may be mediated, to a certain extent, by trans-11 C18:1 regulated by stearoyl-CoA desaturase-1 (SCD1) and/or its syntrophic proteins. This study aimed to investigate the effects of TVA on SCD1-mediated cis-9,trans-11 CLA synthesis in MAC-T cells and its potential molecular mechanism. Results showed that trans-11 C18:1 was continually taken up and converted into cis-9,trans-11 CLA in MAC-T cells during the 4-h incubation of 50?μM trans-11 C18:1. SCD1 protein expression increased more than twofold at 2?h (P?<?0.01) and 2.5?h (P?<?0.05) before decreasing to less than half of the normal level at 4?h (P?<?0.05). One up-regulated (RAS guanyl releasing protein 4 isoform 1 [RASGRP4]) and six down-regulated proteins (glucosamine-6-phosphate deaminase 1 [GNPDA1], triosephosphate isomerase [TPI1], phosphoglycerate mutase 1 [PGAM1], heat shock protein beta-1 [HSPB1], annexin A3 [ANXA3], thiopurine S-methyltransferase [TPMT]) were found in MAC-T cells treated with trans-11 C18:1. Of these seven identified proteins, the presence of GNPDA1 and PGAM1 was verified in several models. More trans-11 C18:1 was taken up after PGAM1 knockdown by small interfering RNA (siRNA). In conclusion, our data suggested that PGAM1 may have a negative relationship with SCD1 and seemed to be involved in cis-9, trans-11 CLA synthesis by facilitating the absorption of trans-11 C18:1 in the bovine mammary gland.</P>

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        Phase II study of S-1 combined with oxaliplatin as therapy for patients with metastatic biliary tract cancer: influence of the <i>CYP2A6</i> polymorphism on pharmacokinetics and clinical activity

        Kim, K-p,Jang, G,Hong, Y S,Lim, H-S,Bae, K-s,Kim, H-S,Lee, S S,Shin, J-G,Lee, J-L,Ryu, M-H,Chang, H-M,Kang, Y-K,Kim, T W Nature Publishing Group 2011 The British journal of cancer Vol.104 No.4

        <P><B>Background:</B></P><P>Advanced biliary cancer is often treated with fluoropyrimidine-based chemotherapy. In this study, we evaluated the efficacy and tolerability of a combination of S-1, an oral fluoropyrimidine prodrug, and oxaliplatin in patients with metastatic biliary cancer.</P><P><B>Methods:</B></P><P>Patients with histologically confirmed metastatic biliary cancer and no history of radiotherapy or chemotherapy were enrolled. Oxaliplatin was administered intravenously (130 mg m<SUP>−2</SUP>), followed by 14-day administration of oral S-1 (40 mg m<SUP>−2</SUP> twice daily) with a subsequent 7-day rest period every 21 days. Pharmacokinetic analysis of S-1 was performed at cycle 1. Patients were genotyped for <I>CYP2A6</I> polymorphisms (<SUP>*</SUP>1, <SUP>*</SUP>4, <SUP>*</SUP>7, <SUP>*</SUP>9 or <SUP>*</SUP>10), and pharmacokinetic and clinical parameters compared according to the <I>CYP2A6</I> genotype.</P><P><B>Results:</B></P><P>In total, 49 patients were evaluated, who received a median of four cycles. The overall response rate was 24.5%. Median progression-free and overall survival was 3.7 and 8.7 months, respectively. The most common haematological grade 3 out of 4 toxicity was neutropenia (14%), while non-hematological grade 3 out of 4 toxicities included anorexia (14%), nausea (12%), asthenia (10%), vomiting (10%), and diarrhoea (4%). Biotransformation of S-1 (AUC<SUB>0−24 h</SUB> of 5-fluorouracil/AUC<SUB>0−24 h</SUB> of tegafur) was 1.85-fold higher for the <I>*1/*1</I> group than for the other groups (90% confidence interval 1.37–2.49). Diarrhoea (<I>P</I>=0.0740), neutropenia (<I>P</I>=0.396), and clinical efficacy (response rate, <I>P</I>=0.583; PFS, <I>P</I>=0.916) were not significantly associated with <I>CYP2A6</I> genotype, despite differences in 5-FU exposure.</P><P><B>Conclusion:</B></P><P>The combination of S-1 and oxaliplatin appears to be active and well tolerated in patients with metastatic biliary cancer, and thus is feasible as a therapeutic modality. <I>CYP2A6</I> genotypes are associated with differences in the biotransformation of S-1. However, the impact of the <I>CYP2A6</I> polymorphism on variations in clinical efficacy or toxicity requires further evaluation.</P>

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        Preparation and characterization of sulfonated amine-poly(ether sulfone)s for proton exchange membrane fuel cell

        Seo, D.W.,Lim, Y.D.,Lee, S.H.,Jeong, Y.G.,Hong, T.W.,Kim, W.G. Pergamon Press ; Elsevier Science Ltd 2010 International journal of hydrogen energy Vol.35 No.23

        Sulfonated amine-poly(ether sulfone)s (S-APES)s were prepared by nitration, reduction and sulfonation of poly(ether sulfone) (ultrason<SUP>(</SUP>R)-S6010). Poly(ether sulfone) was reacted with ammonium nitrate and trifluoroacetic anhydride to produce the nitrated poly(ether sulfone), and was followed by reduction using tin(II)chloride and sodium iodide as reducing agents to give the amino-poly(ether sulfone). The S-APES was obtained by reaction of 1,3-propanesultone and the amino-poly(ether sulfone) (NH<SUB>2</SUB>-PES) with sodium methoxide. The different degrees of nitration and reduction of poly(ether sulfone) were successfully synthesized by an optimized process. The reduction of nitro group to amino was done quantitatively, and this controlled the contents of the sulfonic acid group. The films were converted from salt to acid forms with dilute hydrochloric acid. Different contents of sulfonated unit of the S-APES were studied by FT-IR, <SUP>1</SUP>H NMR spectroscopy, differential scanning calorimetry (DSC), and thermo gravimetric analysis (TGA). Sorption experiments were conducted to observe the interaction of sulfonated polymers with water and methanol. The ion exchange capacity (IEC), a measure of proton conductivity, was evaluated. The S-APES membranes exhibit conductivities (25 <SUP>o</SUP>C) from 1.05 x 10<SUP>-3</SUP> to 4.83 x 10<SUP>-3</SUP> S/cm, water swell from 30.25 to 66.50%, IEC from 0.38 to 0.82 meq/g, and methanol diffusion coefficients from 3.10 x 10<SUP>-7</SUP> to 4.82 x 10<SUP>-7</SUP> cm<SUP>2</SUP>/S at 25 <SUP>o</SUP>C.

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        Association of tumor necrosis factor- gene polymorphisms with advanced stage endometriosis

        Lee, G. H.,Choi, Y. M.,Kim, S. H.,Hong, M. A.,Oh, S. T.,Lim, Y. T.,Moon, S. Y. Oxford University Press 2008 Human reproduction Vol.23 No.4

        <P>BACKGROUND: This study was performed to investigate whether specific haplotypes and several single nucleotide polymorphisms in the promoter region of the tumor necrosis factor (TNF)-alpha gene are associated with the risk of advanced stage endometriosis in a Korean population. METHODS: This study comprised women with (n = 246) or without (n = 248) endometriosis. The TNF:g.[-1031T > C], TNF:g.[-863C > A] and TNF:g.[-857C > T] polymorphism in the TNF-alpha gene were assessed by PCR-restriction fragment length polymorphism analysis, which utilized digestion by BbsI, HypCH4IV and HypCH4IV restriction enzymes, respectively. In silico haplotypes were deduced by using the Haploview version 3.32. RESULTS: The genotype distribution of TNF:g.[-1031T > C] was significantly different between total endometriosis patients and the controls (T/T of 56.9 versus 60.1%, T/C of 35.4 versus 37.5% and C/C of 7.7 versus 2.4%, respectively, P = 0.027). This difference at the TNF:g.[-1031T > C] tends to increase in Stage IV endometriosis (P = 0.01). However, there was no difference in the TNF:g.[-863C > A] and TNF:g.[-857C > T] site between the two groups. Even when the endometriosis cases were subdivided into American Society for Reproductive Medicine Stages III and IV, genotype differences were not found. The CC homozygote at TNF:g.-863 was more frequently found in the controls than Non-CC group (P = 0.04; odds ratio = 0.67; 95% confidence interval = 0.45-0.98). All haplotypes and diplotypes, deduced by in silico analysis, showed no association with subgroups or controls. CONCLUSIONS: Our results suggest that the genotype frequencies at the TNF:g.[-1031T > C] and the TNF:g.[-863C > A] sites may be associated with advanced stage endometriosis in the Korean population.</P>

      • An emerging recombinant cluster of nephropathogenic strains of avian infectious bronchitis virus in Korea

        Lim, T.H.,Lee, H.J.,Lee, D.H.,Lee, Y.N.,Park, J.K.,Youn, H.N.,Kim, M.S.,Lee, J.B.,Park, S.Y.,Choi, I.S.,Song, C.S. Elsevier Science 2011 Infection, genetics and evolution Vol.11 No.3

        The infectious bronchitis virus (IBV) is continuously evolving through point mutation and recombination of their genome, subsequently the emergence of IBV variants complicates disease control. The objective of this study was to investigate genetic characterization of new IBV variants isolated from commercial chicken flocks in Korea collected between 2005 and 2010. Phylogenetic analysis revealed that all new IBV isolates belonged to Korean group II (K-II), which included the nephropathogenic IBV strains. However, the isolates formed a new gene cluster that was distinguished from the two distinct K-II subgroups (KM91-like and QX-like). Recombination events were identified in the S1 gene, with their putative parental strains being the KM91-like or QX-like subgroup. In addition, two crossover sites were observed in the S1 gene of IBV isolates. These results suggest that natural genetic recombination between heterologous strains classified into different genetic groups has occurred and may have caused the emergence of new IBV strains. This finding provides important information on IBV evolution and is essential for the effective control of IB in Korea.

      • Synthesis of the superconducting MgB<sub>2</sub> film on the W-wire by co-evaporation method

        Lim, Y.J.,Park, S.C.,Chung, J.K.,Lee, T.K.,Song, K.J.,Kim, C.J. North-Holland 2010 Physica. C, Superconductivity Vol.470 No.20

        We have synthesized the MgB<SUB>2</SUB>/W composite fiber by depositing MgB<SUB>2</SUB> film on the W-wire with co-evaporation system. Boron was sputtered with the RF-magnetron sputter and magnesium was thermally evaporated simultaneously during deposition. For the uniformity of the deposited layer and the precise stoichiometric compound formation of the MgB<SUB>2</SUB> film layer, specimen holding unit was rotated at a fixed rate and the sputtered rate of B and evaporated rate of Mg were controlled separately. After post-annealing of the MgB<SUB>2</SUB>/W-wire at 600<SUP>o</SUP>C, we could obtain 100-800nm MgB<SUB>2</SUB> layers with uniform composition. Occasionally un-reacted Mg or second phases such as MgWO<SUB>4</SUB> were observed depending on the experimental conditions. The phase evolution and the microstructure of the deposited MgB<SUB>2</SUB> film were investigated with XRD, SEM, and EDS. The superconducting transition temperatures (T<SUB>c</SUB>) and the average critical current density have been measured around ~33.5K and 3.7x10<SUP>3</SUP>A/cm<SUP>2</SUP>, respectively using the physical property measurement system (PPMS 9T, Quantum Design).

      • 군장병의 헌혈을 통한 말라리아 전파의 위험성에 대한 조사

        임채승,김영기,이갑노,염용태,김순덕,김대성,황유성,오홍범,김두성 대한감염학회 1997 감염 Vol.29 No.2

        목적:국내 헌혈 혈액에서 전염병 감염 방지를 위해 시행하는 감염표지자 중 말라리아를 검출하려는 노력은 최근의 비무장지대 내의 군장병에서의 말라리아 재발생에도 불구하고 활성화 되어 있지 않다. 일반적으로 말라리아가 토착화 된 지역을 거주하거나 여행한 사람 중 말라리아에 걸렸거나 치료한 경력 있는 사람은 치료가 끝난 후라도 3년내에는 헌혈을 금지하도록 규정하고 있다. 저자들은 국내 헌혈의 중요 부분(57.8%)을 차지하는 군인에서 헌혈시 말라리아 전파의 위험성을 파악하고자 본 조사를 실시하였다. 방법:1995년 5월에서 1996년 10월까지 군병원에 입원한 환자중 말라리아로 확진된 174명의 환자에서 면담 및 입원 기록을 추적하여 병력과 헌혈 기록을 확인 한 뒤 헌혈장소, 헌혈일, 헌혈 기록을 확인 한 뒤 헌혈장소, 헌혈일, 헌혈 횟수를 조사하여 환자의 증상 발병일과의 간격 및 연관성 분석하였고 이를 기준으로 공혈 혈액의 수혈시 말라리아의 전파 위험성을 평가하였다. 결과:전체 174명의 환자중에서 1회라도 헌혈을 시행한 사람은 70.7%인 123명에 해당하였고 환자의 증상 시작일과 헌혈일과의 간격은 2일에서 평균 2750일(평균 377알, 표준편차 488일)의 분포를 보였다. 증상시작일과 헌혈일의 간격이 3년 이내인 경우는 전체의 87.8%에 해당하였다. 말라리아 치료후 헌혈을 실시한 경우는 (n=18) 모두 치료 후 3년 이내에 헌혈을 하였다. 헌혈장소는 토착형 말라리아의 호발 지역과 동일하였는데 경기도 파주시(40%)와 연천군(29%) 및 철원(15.5%) 기타(15.5%)순이었다. 결론:한국에서 토착형 말라리아 군인 환자들의 병력조회에서 헌혈에 의한 전염가능성이 존재하는 기간 내에 헌혈이 적지 않게 실시되고 있어서 이들 지역에서의 군헌혈을 실시하는 경우 엄격한 헌혈자 선별기준 적용되어야 할 것으로 생각된다. Background: Screening of donor blood for malaria has not been activated in Korea yet in spite of the recent resurgence of tertian malaria among Korean army soldiers in Delimited Militarized Zone areas. Prospective donors(travellers, immigrants, refugees, citizens or residents) following a visit to or coming from and endemic area who have had malaria or taken antimalarial prophylaxis should be deferred for 3 years after cessation of therapy or after depature from malarial area. We studied the risk of the transmission of malaria, especially through army blood donation which comprised up to 57.8% of whole blood donation in Korea. Methods: The data were collected by personal interview and review of donation records of Korea Red Cross Center and medical records from 174 army soldiers with malaria who admitted to Army Hospital from May 1995 to October 1996. We analysed the time interval between onset of illness and blood donation, and geographic distribution of the patients. Results: About 70.7%(123/174) of the patients donated blood before the onset of illness, and the internal between blood donation and onset of illness ranged from 2 days to 2,750 days (mean 377, standard deviation488). Patients who donated blood within 3 years before onset of illness were 87.8%(n=108) of the total blood donation. All donation (n=18) after treatment were within 3 years from 46 days to 342 days(mean 138, standard deviation 80.7). The frequent of blood donations were from the prevalent areas of malaria such as Pajoo City(40%), Younchon Kun(29%), Cholwon Kun(15.5%) and others(15.5%). Conclusion: We showed that donated army blood a risk of malaria transmission. Therefore the blood bank needs to set strict guidelines for blood donation especially from Korean army soldiers to control malaria transmission.

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        Studies of sulfonated polyphenylene membranes containing benzophenone moiety for PEMFC

        Lim, Y.,Lee, S.,Jang, H.,Hossain, Md.A.,Hong, T.,Ju, H.,Hong, T.,Kim, W. Pergamon Press ; Elsevier Science Ltd 2014 International journal of hydrogen energy Vol.39 No.36

        The sulfonated polyphenylenes containing benzophenone structure (sulfonated Parmax 1200, S-Parmax) were prepared by sulfonation reaction of Parmax 1200 with 30% fuming sulfuric acid, and degree of sulfonation was controlled by sulfonation reaction time. These polymers have all carbon structure without ether linkages that have the possibility of attack by nucleophiles (made by PEMFC operating system). The polyphenylene structure of Parmax provides a stiff and resistant backbone, whereas the pendant benzoyl group enables the solubility of the material, and also provides sites for chemical modifications. The structure properties of the synthesized polymers were investigated by <SUP>1</SUP>H NMR spectroscopy. The membranes were studied by ion exchange capacity (IEC), water uptake, and proton conductivity. These membranes deterioration test was performed by Fenton reagent, and compared with normal sulfonated poly(ether sulfone)s and Nafion. The power densities of membranes were performed by single cell.

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      • IAN5 polymorphisms are associated with systemic lupus erythematosus

        Lim, MK,Sheen, DH,Kim, SA,Won, SK,Lee, S-S,Chae, S-C,Chung, H-T,Shim, SC SAGE Publications 2009 Lupus Vol.18 No.12

        <P>Systemic lupus erythematosus (SLE) is a representative autoimmune disease, which is frequently associated with lymphopenia. Biobreeding (BB) rat is a typical animal model which develops autoimmune diseases with lymphopenia which results from a frame-shift mutation in the immune-associated nucleotide (<I>IAN</I>) <I>5</I> gene. <I>IAN5</I> is involved in the regulation of T-cell activation and survival. To examine the association of <I>IAN5</I> gene with SLE, we scrutinised the single nucleotide polymorphisms (SNPs) in the <I>IAN5</I> gene. We conducted a case–control study where 132 SLE patients, 505 rheumatoid arthritis (RA) patients, and 546 controls were genotyped for four SNPs in the <I>IAN5</I> gene. Two SNPs (+2071C?>?T and +2677G?>?A) were associated with susceptibility to SLE (<I>P</I>?=?0.040 and 0.045, respectively), and −4432G?>?A SNP was associated with the development of leukopenia (<I>P</I>?=?0.028) and the requirement of steroid pulse therapy (<I>P</I>?=?0.040) in SLE patients. Haplotype analyses showed that Ht1(CTCG) was associated with susceptibility to SLE (<I>P</I>?=?0.036), and Ht4(ACCG), Ht5(ACTA) and Ht6(GCCG) were associated with the development of nephritis (<I>P</I>?=?0.017, 0.019, 0.022, respectively). In conclusion, the <I>IAN5</I> polymorphisms were associated with susceptibility to SLE and the development of clinical disease manifestations in a strictly Korean population.</P>

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