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      • KCI등재

        Effect of calcineurin inhibitor on post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with liver transplantation: a propensitymatched cohort study

        Hyoung-Chul Oh,Jeffrey J. Easler,Ihab I. El Hajj,James Watkins,Evan L. Fogel,Lee McHenry,Stuart Sherman,Hyun Kang,Glen A. Lehman 대한내과학회 2020 The Korean Journal of Internal Medicine Vol.35 No.6

        Background/Aims: A calcineurin inhibitor may alter pancreatic function and inflammatory reaction. This study aimed to determine the possible pharmacologic effect of the calcineurin inhibitor, tacrolimus, on pancreatic function, and to determine its preventive effect on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in liver transplantation (LT) patients. Methods: The serum amylase and lipase values before and after LT were compared. The frequency of post-ERCP pancreatitis was compared between non-LT and LT patients, using propensity score matching method. Results: Median serum amylase values (normal range, 19 to 86 U/L) were 49.0 U/L (38.0 to 68.0) before LT and 27.0 U/L (19.3 to 36.8) after LT, and median serum lipase values (normal range, 7 to 59 U/L) were 40.0 U/L (26.5 to 54.0) before LT and 10.5 U/L (6.0 to 21.0) after LT. Both serum amylase and lipase values significantly decreased after LT (p < 0.001), and to a level comparable to chronic pancreatitis. There was a marginal significant difference between the non-LT and LT groups before the propensity score matching with respect to frequency of post-ERCP pancreatitis (16 [3.2%] in non-LT group vs. 2 [0.9%] in LT group, p = 0.069). After propensity score matching, a marginal significant difference still existed with respect to frequency of post-ERCP pancreatitis (7 [4.8%] in non-LT group vs. 1 [0.7%] in LT group, p = 0.067). Conclusions: The immunosuppression with calcineurin inhibitor may reduce not only the pancreatic enzyme dynamics but also inciting inflammatory event including post-ERCP pancreatitis.

      • KCI등재

        Low Serum Pancreatic Amylase and Lipase Values Are Simple and Useful Predictors to Diagnose Chronic Pancreatitis

        ( Hyoung-chul Oh ),( Chang-il Kwon ),( Ihab I. El Hajj ),( Jeffrey J. Easler ),( James Watkins ),( Evan L. Fogel ),( Lee Mchenry ),( Stuart Sherman ),( Michelle K. Zimmerman ),( Glen A. Lehman ) 대한간학회 2017 Gut and Liver Vol.11 No.6

        Background/Aims: This study aimed to evaluate the diagnostic role of low serum amylase and lipase values in the detection of chronic pancreatitis. Methods: Patients underwent endoscopic retrograde cholangiopancreatography and were diagnosed with non-calcific chronic pancreatitis (NCCP; n=99) and calcific chronic pancreatitis (CCP; n=112). Patient serum amylase and lipase values were compared with those of healthy controls (H; n=170). Results: The median serum amylase (normal range, 19 to 86 U/L) and lipase values (7 to 59 U/L) (P25-P75) were 47.0 (39.8 to 55.3) and 25.0 (18.0 to 35.0) for H, 34.0 (24.5 to 49.0) and 19.0 (9.0 to 30.0) for NCCP, and 30.0 (20.0 to 40.8) and 10.0 (3.0 to 19.0) for CCP, respectively. The cutoff values with the highest diagnostic accuracy for discriminating NCCP from H were 40 U/L for amylase and 20 U/L for lipase, respectively, and for CCP from H were 38 U/L for amylase and 15 U/L for lipase, respectively. For the diagnosis of NCCP with a criterion of serum amylase <40 and lipase <20 U/L, the sensitivity, specificity, positive predictive value, and negative predictive values were 37.4%, 88.8%, 66.1%, and 70.9%, respectively. Conclusions: Serum amylase and/or lipase levels below the normal serum range are highly specific for chronic pancreatitis patients. Clinicians should not ignore low serum pancreatic enzyme values. (Gut Liver 2017;11:878-883)

      • SCIEKCI등재

        Functional Implication of the tRNA Genes Encoded in the Chlorella Virus PBCV-l Genome

        Lee, Da-Young,Graves, Michael V.,Van Etten, James L.,Choi, Tae-Jin The Korean Society of Plant Pathology 2005 Plant Pathology Journal Vol.21 No.4

        The prototype Chlorella virus PBCV-l encodes 11 tRNA genes and over 350 protein-encoding genes in its 330 kbp genome. Initial attempts to overexpress the recombinant A189/192R protein, a putative virus attachment protein, in E. coli strain BL21(DE3) SI were unsuccessful, and multiple protein bands were detected on Western blots. However, the full-length A189/192R recombinant protein or fragments derived from it were detected when they were expressed in E. coli BL21 CodonPlus (DE3) RIL, which contains extra tRNAs. Codon usage analysis of the a189/192r gene showed highly biased usage of the AGA and AVA codons compared to genes encoded by E. coli and Chlorella. In addition, there were biases of XXA/U($56\%$) and XXG/ C($44\%$) in the codons recognized by the viral tRNAs, which correspond to the codon usage bias in the PBCV-1 genome of XXA/U ($63\%$) over those ending in XXC/G ($37\%$). Analysis of the codon usage in the major capsid protein and DNA polymerase showed preferential usage of codons that can be recognized by the viral tRNAs. The Asn (AAC) and Lys (AAG) codons whose corresponding tRNA genes are duplicated in the tRNA gene cluster were the most abundant (i.e., preferred) codons in these two proteins. The tRNA genes encoded in the PBCV-l genome seem to play a very important role during the synthesis of viral proteins through supplementing the tRNAs that are frequently used in viral proteins, but are rare in the host cells. In addition, these tRNAs would help the virus to adapt to a wide range of hosts by providing tRNAs that are rare in the host cells.

      • SCISCIESCOPUS

        Regulator of Fatty Acid Metabolism, Acetyl Coenzyme A Carboxylase 1, Controls T Cell Immunity

        Lee, JangEun,Walsh, Matthew C.,Hoehn, Kyle L.,James, David E.,Wherry, E. John,Choi, Yongwon American Association of Immunologists 2014 Journal of Immunology Vol. No.

        <P>Fatty acids (FAs) are essential constituents of cell membranes, signaling molecules, and bioenergetic substrates. Because CD8<SUP>+</SUP> T cells undergo both functional and metabolic changes during activation and differentiation, dynamic changes in FA metabolism also occur. However, the contributions of de novo lipogenesis to acquisition and maintenance of CD8<SUP>+</SUP> T cell function are unclear. In this article, we demonstrate the role of FA synthesis in CD8<SUP>+</SUP> T cell immunity. T cell–specific deletion of acetyl coenzyme A carboxylase 1 (ACC1), an enzyme that catalyzes conversion of acetyl coenzyme A to malonyl coenzyme A, a carbon donor for long-chain FA synthesis, resulted in impaired peripheral persistence and homeostatic proliferation of CD8<SUP>+</SUP> T cells in naive mice. Loss of ACC1 did not compromise effector CD8<SUP>+</SUP> T cell differentiation upon listeria infection but did result in a severe defect in Ag-specific CD8<SUP>+</SUP> T cell accumulation because of increased death of proliferating cells. Furthermore, in vitro mitogenic stimulation demonstrated that defective blasting and survival of ACC1-deficient CD8<SUP>+</SUP> T cells could be rescued by provision of exogenous FA. These results suggest an essential role for ACC1-mediated de novo lipogenesis as a regulator of CD8<SUP>+</SUP> T cell expansion, and may provide insights for therapeutic targets for interventions in autoimmune diseases, cancer, and chronic infections.</P>

      • Hautmann and Studer orthotopic neobladders : the Michigan experience 미시간 대학병원 경험

        Lee, Kyung Seop,Montie, James E.,Dunn, Rodney L.,Lee, Cheryl T. 東國大學校醫學硏究所 2002 東國醫學 Vol.9 No.2

        연구목적 : 요로전환술의 치료에 있어서 Hautmann과 Studer 정위방광대치술은 획기적인 방법이다. 이에 저자들은 Hautmann과 Studer 정위방광대치술을 시행했던 환자들을 대상으로 임상적 결과를 후향적으로 분석하였다. 대상 및 방법 : 1995년 3월 1일부터 2000년 9월 30일까지 미시간 대학 병원 비뇨기과에서 방광종양으로 방광절제술 후 Hautmann과 Studer 정위방광대치술을 시행받았던 130명(Hautmann 37명, Studer 93명)을 대상으로 하였다. 이 환자들을 대상으로 두 술식에 대한 환자의 나이, 성, 수술 소요 시간, 입원 기간, 수술 중 출혈 양, 병리학적 병기와 합병증율, 요자제율 및 재수술률을 비교분석해 보았다. 통계적 분석은 Fishers exact test, T-test와 Wilcoxon rank-sum 분석을 이용하였다. 결과 : Hautmann과 Studer 정위방광대치술에 걸린 수술 시간은 각각 5.9, 5.3시간이었다(p=0.003). 입원 기간은 7일과 8.3일로 Hautmann 정위방광대치술이 짧았다(p=0.02). 그 외 나이, 성, 수술 중 출혈 양, 병리학적 병기와 합병증률 및 재수술률은 차이를 보이지 않았다. 요 자제율은 Hautmann과 Studer 정위방광대치술 각각에서 낮 시간은 67%로 같았으며 밤 시간에는 47%와 40%로 비슷하였다. 결론 : Hautmann과 Studer 정위방광대치술 두 술식 모두 안전하고 쉽게 시행할 수 있는 좋은 방법이며 요 자제율 면에서 Hautmann 정위방광대치술이 좀 더 나은 것 같으나 통계적으로 유의하지는 않았다. 또한 Hautmann 정위방광대치술이 수술 시간이 좀 덜 걸리는 것은 요관문합에서의 차이로 생각되며 입원 기간 역시 좀 더 빨리 퇴원을 종용한 결과로 생각된다. Objectives: The development of Studer and Hautmann orthotopic neobladders has revolutionized the management of urinary diversion. Several series have promoted one technique over the other This study examines the clinical outcome of a contemporary cohort of bladder cancer patients who underwent either Hautmann or Studer orthotopic reconstruction. Materials and Methods: Retrospective analysis was performed on 130 patients (93 Studer and 37 Hautmann) who underwent cystectomy and orthotopic diversion between 1st march. 1995 and 30th September 2000. Clinical parameters evaluated were age, gender, procedure time, length of hospital stay, blood loss, pathologic stage, and rate of complication, continence, and reoperation. Diversion type was compared with clinical parameters using the Fishers exact Test, t-test, and Wilcoxon rank-sum analysis. Results: Studer and Hautmann techniques had mean procedure times of 5.9 and 5.3 hours, respectively (p=0.003); Hautmann patients also had a shorter mean length of hospital stay (LOS) (7.0 vs 8.3 days, respectively; p=0.02). When comparing both populations, there was no difference in age, gender, estimated blood loss (EBL), pathologic stage, or rate of complication or reoperation. Total continence was similar in the Hautmann and Studer cohorts, whether during daytime (67% vs 67%) or nighttime (47% vs 40%) hours, respectively. Conclusions: The data suggests that both orthotopic techniques can be performed in men and women in a safe and timely fashion. Continence rates appear better with the Hautmann technique, though the limited cohort size did not offer sufficient power to detect a statistical difference. The shortened procedure time in Hautmann patients likely relates to variations in th ureteral anastomosis. Decreased LOS may reflect recent trends of early patient discharge.

      • SCIESCOPUSKCI등재

        Batch Variation and Pharmacokinetics of Oral Sustained Release Melatonin-loaded Sugar Spheres in Human Subjects

        Lee, Beom-Jin,Ryu, Seung-Goo,Choi, Han-Gon,Kim, Chong-Kook,Parrott, Keith-A.,Ayres, James-W.,Sack, Robert-L. The Pharmaceutical Society of Korea 1997 Archives of Pharmacal Research Vol.20 No.6

        The three different batches of an oral sustained release melatonin (MT) delivery system were prepared by aqueous-based fluid-bed coating of the sugar spheres for the evaluation of in vitro release characteristics and plasma concentration profiles in human subjects. The MT contents in 20% coated sugar spheres of three batches (B1, B2 and B3) were $3.3{\pm}0.08$, $2.4{\pm}0.1$ and $2.5{\pm}0.13$ mg per gram of coated sugar spheres, respectively. The release profiles of three different batches had a very similar fashion. However, the release profiles of three different batches had a very similar fashion. However, the release half-lives $(T_{50%})$ of MT from B1, B2 and B3 was $3.70{\pm}0.2$, $5.2{\pm}0.2$ and $4.9{\pm}0.07h$, respectively. Plasma concentration profiles of sustained release 0.2mg melatonin-loaded sugar spheres containing 10% immediate release melatonin in gelatin capsules (B1 and B2) were then evaluated in human subjects. The in vivo plasma concentration profies of the two batches (B1 and B2) were very similar each other and located between the physiological endogenous ranges. The time to reach the peak concentration $(T_max)$ was more advanced in case of B1 when compared to B2. However, there was no statistically significant difference in the maximum concentration $(C_max)$ and the area under the curve (AUC) between B1 and B2. The AUC of melatonin-loaded sugar spheres containing 10% and 20% immediate release MT in human subjects had a good linearity between dose and AUC, regardless of the fraction of immediate release MT, indicating the first order elimination process of MT within these doses. The current oral sustained release MT delivery system may be utilized to treat circadian rhythm disorders if it is proven to be more clinically useful when compared to immediate release MT.

      • SCOPUSKCI등재

        Development and Evaluation of an Oral Controlled Release Delivery System for Melatonin

        Lee,Beom Jin,Keith A Parrott,Robert L Sack,James W Ayres 한국약제학회 1993 Journal of Pharmaceutical Investigation Vol.23 No.3

        Sugar spheres loaded with melatonin (MT) were coated with Aquacoat^ⓡ to control the release rate of MT over 8 hours. A zero-order release pattern over 8 hours was obtained with 20% coating on 8-10 mesh beads in USP basket dissolution studies. MT in 20% coated beads was quite stable at room temperature with less than 5% MT degraded during 6 months' storage. Dissolution profiles were also unchanged after 6 months. An oral preparation containing MT-loaded uncoated beads for immediate release and 20% coated beads with Aquacoat^ⓡ for controlled release over 8 hours was evaluated in six human subjects. When total 0.5 ㎎ MT as low dose (immediate release portion of MT, 0.1 ㎎) was administered to four subjects, average peak plasma MT concentration was reached at about 600 pg/㎖ and maintained at about 10 pg/㎖ over 8 hours. Plasma MT concentration-time profiles were similar in shape to computer-simulated profiles. However, maximal plasma MT concentrations were three times greater compared to computer simulated curve. These results suggest that MT dose, ratio of immediate and controlled release MT, and pharmacokinetic parameters selected are adjusted to mimic endogenous MT concentration-time curve. In another study, 0.2 ㎎ MT having 10% of immediate release portion and 80% controlled release portion produced plasma MT concentration-time curve which is more similar to endogenous profiles. A low bioavailability (<20%) may result from extensive first pass metabolism and remaining amounts of MT from controlled beads. A good correlation between plasma MT concentration and urinary excretion rate of 6-sulphatoxymelatonin (6-STMT), a major metabolite of MT was observed. As plasma MT concentration increased, urinary excretion rate of 6-STMT increased concomitantly. The linear relation between plasma MT and urinary excretion rate of 6-STMT was statistically significant. This result suggests that urinary 6-STMT may be used as an index of circadian rhythms of MT in humans.

      • Noninvasive Measurement of Electrical Events Associated with a Single Chlorovirus Infection of a Microalgal Cell

        Lee, Seung-Woo,Lee, Eun-Hee,Thiel, Gerhard,Van Etten, James L.,Saraf, Ravi F. American Chemical Society 2016 ACS NANO Vol.10 No.5

        <P>Chlorovirus Paramecium bursaria chlorella virus 1 (PBCV-1) contains a viral-encoded K+ channel imbedded in its internal membrane, which triggers host plasma membrane depolarization during virus infection. This early stage of infection was monitored at high resolution by recording the cell membrane depolarization of a single Chlorella cell during infection by a single PBCV-1 particle. The measurement was achieved by depositing the cells onto a network of one-dimensional necklaces of Au nanoparticles, which spanned two electrodes 70 mu m apart. The nanoparticle necklace array has been shown to behave as a single-electron device at room temperature. The resulting electrochemical field-effect transistor (eFET) was gated by the cell membrane potential, which allowed a quantitative measurement of the electrophysiological changes across the rigid cell wall of the microalgae due to a single viral attack at high sensitivity. The single viral infection signature was quantitatively confirmed by coupling the eFET measurement with a method in which a single viral particle was delivered for infection by a scanning probe microscope cantilever.</P>

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