말라리아박멸을 위한 조사연구 : 1. 말라리아 유행지역 주민의 항체보유율 변화 1. The study for the malaria eradication 1. The seasonal changes of antibodies of inhabitants lived in malaria epidemic areas

김동수,이형우,조신형,인태숙,이혜정,이욱교,김남렬,신민철,문승욱,임현정,고승연,이종수 국립보건연구원 2000 국립보건원보 Vol.37 No.-

Loss of NDRG2 promotes epithelial-mesenchymal transition of gallbladder carcinoma cells through MMP-19-mediated Slug expression

Lee, D.G.,Lee, S.H.,Kim, J.S.,Park, J.,Cho, Y.L.,Kim, K.S.,Jo, D.Y.,Song, I.C.,Kim, N.,Yun, H.J.,Park, Y.J.,Lee, S.J.,Lee, H.G.,Bae, K.H.,Lee, S.C.,Shim, S.,Kim, Y.M.,Kwon, Y.G.,Kim, J.M.,Lee, H.J.,Mi Elsevier Science Publishers 2015 Journal of hepatology Vol.63 No.6

Background & Aims: Gallbladder carcinoma (GBC) is the most common malignancy of the biliary tract and one of the most lethal forms of human cancer. However, there is limited information about the molecular pathogenesis of GBC. Here, we examined the functional role of the tumor suppressor N-myc downstream-regulated gene 2 (NDRG2) and the underlying molecular mechanisms of disease progression in GBC. Methods: Clinical correlations between NDRG2 expression and clinicopathological factors were determined by immunohistochemical analysis of tumor tissues from 86 GBC patients. Biological functions of NDRG2 and NDRG2-mediated signaling pathways were determined in GBC cell lines with NDRG2 knockdown or overexpression. Results: Loss of NDRG2 expression was an independent predictor of decreased survival and was significantly associated with a more advanced T stage, higher cellular grade, and lymphatic invasion in patients with GBC. GBC cells with loss of NDRG2 expression showed significantly enhanced proliferation, migration, and invasiveness in vitro, and tumor growth and metastasis in vivo. Loss of NDRG2 induced the expression of matrix metalloproteinase-19 (MMP-19), which regulated the expression of Slug at the transcriptional level. In addition, MMP-19-induced Slug, increased the expression of a receptor tyrosine kinase, Axl, which maintained Slug expression through a positive feedback loop, and stabilized epithelial-mesenchymal transition of GBC cells. Conclusions: The results of our study help to explain why the loss of NDRG2 expression is closely correlated with malignancy of GBC. These results strongly suggest that NDRG2 could be a favorable prognostic indicator and promising target for therapeutic agents against GBC.

Reduced-Intensity Conditioning with Busulfan, Fludarabine, and Antithymocyte Globulin for Hematopoietic Cell Transplantation from Unrelated or Haploidentical Family Donors in Patients with Acute Myeloid Leukemia in Remission

Lee, K.H.,Lee, J.H.,Lee, J.H.,Kim, D.Y.,Park, H.S.,Choi, E.J.,Ko, S.H.,Seol, M.,Lee, Y.S.,Kang, Y.A.,Jeon, M.,Baek, S.,Kang, Y.L.,Kim, S.H.,Yun, S.C.,Kim, H.,Jo, J.C.,Choi, Y.,Joo, Y.D.,Lim, S.N. Kluge Carden Jennings Pub. Co 2017 BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Vol.23 No.9

To investigate the role of antithymocyte globulin (ATG)-containing reduced-intensity conditioning (RIC) in hematopoietic cell transplantation (HCT) from unrelated (UD) or haploidentical family donors (HFD), we conducted a phase 2 trial of 237 patients (age range, 16 to 69 years) with acute myeloid leukemia (AML) in remission. Patients undergoing UD-HCT (n@?=@?93) or HFD-HCT (n@?=@?59) received RIC comprising busulfan, fludarabine, and ATG, 9@?mg/kg, whereas those undergoing HCT from matched sibling donors (MSD, n@?=@?85) received myeloablative busulfan and cyclophosphamide conditioning or aforementioned RIC with ATG, 4.5@?mg/kg. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine and methotrexate were administered. The median follow-up period was 44.7 months after HCT for 161 survivors. For UD-HCT versus HFD-HCT, there were no significant differences in leukemia recurrence, nonrelapse mortality, relapse-free survival, grades 2 to 4 acute GVHD, and moderate-to-severe chronic GVHD. Furthermore, when the outcomes of UD-HCT and HFD-HCT were combined and compared with those of MSD-HCT, there were no significant differences in leukemia recurrence (3-year cumulative incidence, 30% versus 29%), nonrelapse mortality (3-year cumulative incidence, 7% versus 8%), relapse-free survival (3-year estimate, 63% versus 63%), and grades 2 to 4 acute GVHD (120-day cumulative incidence, 16% versus 13%). Moderate-to-severe chronic GVHD, however, occurred less frequently in UD/HFD-HCT (2-year cumulative incidence, 22% versus 40%; P@?=@?.006). The addition of ATG to conditioning regimen was a significant predictor for less chronic GVHD (subdistribution hazard ratio, .59). In AML in remission, UD/HFD-HCT after ATG-containing RIC achieved leukemia control equivalent to that of MSD-HCT. Despite HLA disparity in UD/HFD-HCT, chronic GVHD occurred less frequently after ATG-containing RIC, suggesting a strong GVHD-modulating effect of ATG.

Thermal-Annealing Eect on the Diode Characteristics of n-ZnO/p-Si (111)

J. H. Lee,J. Y. Lee,J. J. Kim,N. W. Jang,H. K. Cho,조채룡,H. S. Kim 한국물리학회 2009 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.54 No.2

Zinc-oxide films were deposited, by a RF (radio-frequency) sputtering system, on p-type Si (111) substrates at room temperature. The films were annealed at various temperatures in order to study the annealing temperature dependence of the diode characteristics of n-ZnO/p-Si (111). An n-ZnO/p-Si heterojunction diode was fabricated by using a photolithographic method. The diode characteristics were investigated by using current - voltage measurements (HP4145B). The effect of annealing temperature on the structural and the morphological property was investigated by using X-ray diffraction (XRD) and atomic force microscopy (AFM). The turn-on voltage of the diodes was about 1.4~1.7 V and the current-voltage curve revealed an excellent rectification behavior. The diode characteristics changed with annealing temperature and n-ZnO/p-Si (111) heterojunction diodes exhibited yellow light at 13 ~ 15 V. Zinc-oxide films were deposited, by a RF (radio-frequency) sputtering system, on p-type Si (111) substrates at room temperature. The films were annealed at various temperatures in order to study the annealing temperature dependence of the diode characteristics of n-ZnO/p-Si (111). An n-ZnO/p-Si heterojunction diode was fabricated by using a photolithographic method. The diode characteristics were investigated by using current - voltage measurements (HP4145B). The effect of annealing temperature on the structural and the morphological property was investigated by using X-ray diffraction (XRD) and atomic force microscopy (AFM). The turn-on voltage of the diodes was about 1.4~1.7 V and the current-voltage curve revealed an excellent rectification behavior. The diode characteristics changed with annealing temperature and n-ZnO/p-Si (111) heterojunction diodes exhibited yellow light at 13 ~ 15 V.

Allogeneic hematopoietic cell transplantation for myelodysplastic syndrome: prognostic significance of pre-transplant IPSS score and comorbidity

Lee, J-H,Lee, J-H,Lim, S-N,Kim, D-Y,Kim, S H,Lee, Y-S,Kang, Y-A,Kang, S-I,Jeon, M J,Seol, M,Seo, E-J,Chi, H S,Park, C J,Jang, S,Yun, S-C,Lee, K-H Macmillan Publishers Limited 2010 BONE MARROW TRANSPLANTATION -BASINGSTOKE- Vol.45 No.3

We analyzed the clinical significance of pre-transplant International Prognostic Scoring System (IPSS) score and comorbidity in 68 patients who underwent allogeneic hematopoietic cell transplantation (HCT) for myelodysplastic syndrome (MDS) (n=48) or acute myeloid leukemia evolved from MDS (n=20) between December 1995 and January 2008 in a single institute. During a median follow-up period of 41.0 months (range, 3.2–132.0 months), 27 patients died, and 7 relapsed. The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 60.0 and 57.4%, respectively, and the 5-year cumulative incidences of non-relapse mortality (CINRM) and relapse were 32.7 and 9.9%, respectively. OS, EFS, and CINRM were significantly different according to pre-transplant IPSS score and presence of pre-transplant comorbidity, which were independent risk factors along with Karnofsky performance score in multivariate analyses. In conclusion, pre-transplant IPSS score and comorbidity may stratify the risk of post transplant outcomes in MDS.

Indomethacin preconditioning induces ischemic tolerance by modifying zinc availability in the brain

Lee, J.Y.,Oh, S.B.,Hwang, J.J.,Suh, N.,Jo, D.G.,Kim, J.S.,Koh, J.Y. Blackwell Science ; Academic Press 2015 Neurobiology of disease Vol.81 No.-

Intracellular zinc overload causes neuronal injury during the course of neurological disorders, whereas mild levels of zinc are beneficial to neurons. Previous reports indicated that non-steroidal anti-inflammatory drugs, including indomethacin and aspirin, can reduce the risk of ischemic stroke. This study found that chronic pretreatment of rats with indomethacin, a non-selective cyclooxygenase inhibitor, provided tolerance to ischemic injuries in an animal model of stroke by eliciting moderate zinc elevation in neurons. Consecutive intraperitoneal injection of indomethacin (3mg/kg/day for 28days) led to modest increases in intraneuronal zinc as well as synaptic zinc content, with no significant stimulation of neuronal death. Furthermore, indomethacin induced the expressions of intracellular zinc homeostatic and neuroprotective proteins, rendering the brain resistant against ischemic damages and improving neurological outcomes. However, administration of a zinc-chelator, N,N,N',N'-tetra(2-picolyl)ethylenediamine (TPEN; 15mg/kg/day), immediately after indomethacin administration eliminated the beneficial actions of the drug. Therefore, indomethacin preconditioning can modulate intracellular zinc availability, contributing to ischemic tolerance in the brain after stroke.

Impact of low dose atorvastatin on development of new-onset diabetes mellitus in Asian population: Three-year clinical outcomes

Park, J.Y.,Rha, S.W.,Choi, B.,Choi, J.W.,Ryu, S.K.,Kim, S.,Noh, Y.K.,Choi, S.Y.,Akkala, R.G.,Li, H.,Ali, J.,Xu, S.,Ngow, H.A.,Lee, J.J.,Lee, G.N.,Kim, J.,Lee, S.,Na, J.O.,Choi, C.U.,Lim, H.E.,Kim, J.W Elsevier/North-Holland Biomedical Press 2015 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.184 No.-

Background: High dose atorvastatin is known to be associated with new onset diabetes mellitus (NODM) in patients with high risk for developing diabetes mellitus (DM). However, low dose atorvastatin is more commonly used as compared with high dose atorvastatin. The aim of this study is to investigate the impact of low dose atorvastatin (LDA, 10mg or 20mg) on the development of NODM up to three years in Asian patients. Methods: From January 2004 to September 2009, we investigated a total of 3566 patients who did not have DM. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM (C-statistics: 0.851), a total of 818 patients (LDA group, n=409 patients and control group, n=409 patients) were enrolled for analysis. Results: Before PSM, the cumulative incidence of NODM (5.8% vs. 2.1%, p<0.001), myocardial infarction (0.5% vs. 0.1%, p-value=0.007), and major adverse cardio-cerebral event (MACCE, 1.8% vs. 0.7%, p-value=0.012) at three-years were higher in the LAD group. However, after PSM, there was a trend toward higher incidence of NODM (5.9% vs. 3.2%, p=0.064) in the LDA group, but the incidence of MACCE (1.2% vs. 1.5%, p-value=1.000) was similar between the two groups. In multivariable analysis, the LDA administration was tended to be an independent predictor of NODM (OR: 1.99, 95% CI: 1.00-3.98, p-value 0.050). Conclusions: In this study, the use of LDA tended to be a risk factor for NODM in Asian patients and reduced clinical events similar to the control group. However, large-scale randomized controlled trials will be needed to get the final conclusion.

Control of phonon transport by the formation of the Al2O3 interlayer in Al2O3-ZnO superlattice thin films and their in-plane thermoelectric energy generator performance

Park, N. W.,Ahn, J. Y.,Park, T. H.,Lee, J. H.,Lee, W. Y.,Cho, K.,Yoon, Y. G.,Choi, C. J.,Park, J. S.,Lee, S. K. Royal Society of Chemistry 2017 Nanoscale Vol.9 No.21

<P>Recently, significant progress has been made in increasing the figure-of-merit (ZT) of various nanostructured materials, including thin-film and quantum dot superlattice structures. Studies have focused on the size reduction and control of the surface or interface of nanostructured materials since these approaches enhance the thermopower and phonon scattering in quantum and superlattice structures. Currently, bismuth-tellurium-based semiconductor materials are widely employed for thermoelectric (TE) devices such as TE energy generators and coolers, in addition to other sensors, for use at temperatures under 400 K. However, new and promising TE materials with enhanced TE performance, including doped zinc oxide (ZnO) multilayer or superlattice thin films, are also required for designing solid-state TE power generating devices with the maximum output power density and for investigating the physics of in-plane TE generators. Herein, we report the growth of Al2O3/ZnO (AO/ZnO) superlattice thin films, which were prepared by atomic layer deposition (ALD), and the evaluation of their electrical and TE properties. All the in-plane TE properties, including the Seebeck coefficient (S), electrical conductivity (sigma), and thermal conductivity (kappa), of the AO/ZnO superlattice (with a 0.82 nm-thick AO layer) and AO/ZnO films (with a 0.13 nm-thick AO layer) were evaluated in the temperature range 40-300 K, and the measured S, s, and. were -62.4 and -17.5 mu V K-1, 113 and 847 (Omega cm)(-1), and 0.96 and 1.04 W m(-1) K-1, respectively, at 300 K. Consequently, the in-plane TE ZT factor of AO/ZnO superlattice films was found to be similar to 0.014, which is approximately two times more than that of AO/ZnO films (ZT of similar to 0.007) at 300 K. Furthermore, the electrical power generation efficiency of the TE energy generator consisting of four couples of n-AO/ZnO superlattice films and p-Bi0.5Sb1.5Te3 (p-BST) thin-film legs on the substrate was demonstrated. Surprisingly, the output power of the 100 nm-thick n-AO/ZnO superlattice film/p-BST TE energy generator was determined to be similar to 1.0 nW at a temperature difference of 80 K, corresponding to a significant improvement of similar to 130% and similar to 220% compared to the 100 nm-thick AO/ZnO film/p-BST and n-BT/p-BST film generators, respectively, owing to the enhancement of the TE properties, including the power factor of the superlattice film.</P>

Routine preprocedural transesophageal echocardiography might not be necessary for stroke prevention evaluation in AF patients on anticoagulation therapy

Han, J.H.,Shin, D.H.,Lee, H.J.,Kim, Y.J.,Lee, S.H.,Shim, J.,Uhm, J.S.,Kim, J.Y.,Chang, H.J.,Pak, H.N.,Lee, M.H.,Joung, B. Elsevier/North-Holland Biomedical Press 2013 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.168 No.3

Background: Preprocedural transesophageal echocardiography (TEE) is used to reduce the stroke during atrial fibrillation (AF) ablation. This study evaluated whether routine preprocedural TEE in addition to multidetector computed tomography (MDCT) is necessary to prevent periprocedural stroke in AF ablation. Methods: Each patient underwent MDCT and TEE (group 1, n=247) or MDCT alone (group 2, n=103) for the initial evaluation before AF ablation. In group 2, TEE was performed only in patients who had left atrial (LA) thrombus or blood stasis in MDCT. Results: There was no difference in sex, CHADS<SUB>2</SUB> score, or LA dimension between the two groups. In group 1, a thrombus was detected in 12 (5%) and 6 (2%) patients by the MDCT and TEE, respectively. All (100%) patients, who were revealed to have thrombus in TEE, also had a thrombus in MDCT. In group 2, 3 (3%) patients exhibited LA thrombus in MDCT, among whom thrombus was observed in only one patient (1%) in TEE. AF ablation was not performed in patients with thrombus. While one patient had a periprocedural stroke in group 1, no patient had in group 2 (P=0.52). Conclusion: The overall periprocedural stroke rate was low (0.3%) in AF patients on anticoagulation therapy. The preprocedural MDCT detected all patients with the LA thrombus. In AF patients with low CHADS2 score, optimal anticoagulation and relatively preserved left ventricular ejection fraction, routine preprocedural TEE in addition to the MDCT might not be necessary to decrease the periprocedural stroke rate.

Direct analysis of site-specific N-glycopeptides of serological proteins in dried blood spot samples

Choi, N. Y.,Hwang, H.,Ji, E. S.,Park, G. W.,Lee, J. Y.,Lee, H. K.,Kim, J. Y.,Yoo, J. S. Springer Science + Business Media 2017 Analytical and Bioanalytical Chemistry Vol.409 No.21

<P>Dried blood spot (DBS) samples have a number of advantages, especially with respect to ease of collection, transportation, and storage and to reduce biohazard risk. N-glycosylation is a major post-translational modification of proteins in human blood that is related to a variety of biological functions, including metastasis, cell-cell interactions, inflammation, and immunization. Here, we directly analyzed tryptic N-glycopeptides from glycoproteins in DBS samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) without centrifugation of blood samples, depletion of major proteins, desalting of tryptic peptides, and enrichment of N-glycopeptides. Using this simple method, we identified a total of 41 site-specific N-glycopeptides from 16 glycoproteins in the DBS samples, from immunoglobulin gamma 1 (IgG-1, 10 mg/mL) down to complement component C7 (50 mu g/mL). Of these, 32 N-glycopeptides from 14 glycoproteins were consistently quantified over 180 days stored at room temperature. The major abundant glycoproteins in the DBS samples were IgG-1 and IgG-2, which contain nine asialo-fucosylated complex types of 16 different N-glycopeptide isoforms. Sialo-non-fucosylated complex types were primarily detected in the other glycoproteins such as alpha-1-acid glycoprotein 1, 2, alpha-1-antitypsin, alpha-2-macroglobulin, haptoglobin, hemopexin, Ig alpha 1, 2 chain C region, kininogen-1, prothrombin, and serotransferrin. We first report the characterization of site-specific N-glycoproteins in DBS samples by LC-MS/MS with minimal sample preparation.</P>