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Early response in macrophages by exposure to a low concentration of anthrax lethal toxin
정경화,JeongAh Nam,Ji Cheon Kim,Seoung Joo Kim,Kwang Gun Oh,Sanghoon Kim,채영규 대한독성 유전단백체 학회 2011 Molecular & cellular toxicology Vol.7 No.1
The central role in the pathogenesis of anthrax is played by the two classical anthrax toxins. Three factors that are secreted by the bacterium combine to form two bipartite toxins. Edema toxin, consisting of the protective antigen (PA) and the edema factor (EF), causes the edema associated with anthrax infection. Lethal toxin (LeTx), composed of PA and the lethal factor (LF), is believed to be responsible for causing death in systemic anthrax infections. LF is a zinc-dependent endoproteinase that cleaves the N-terminus of mitogen-activated protein kinase kinases (MAPKKs) and functionally impairs cells of both the innate and adaptive immune systems. To analyze the cellular mechanisms underlying the host-pathogen interaction in anthrax infection, we examined the murine macrophage cell line RAW 264.7 following treatment with a relatively low concentration of LeTx (0.1μg/mL of PA, 0.1 μg/mL of LF). Analysis of the gene expression pattern of macrophages treated with low concentrations of LeTx indicated changes in the expression levels of many genes 90 min after toxin treatment. These genes represent the early response in intoxicated macrophages and may contribute to the identification of survival or death factors. Additionally,we demonstrate that the activation of the putative phosphatase and tensin homology on chromosome 10(PTEN) signal transduction pathway regulates cell death by decreasing the levels of phosphorylated glycogen synthase kinase 3β (GSK-3β) through activation of protein phosphatase 1 catalytic subunit alpha (PP1c)in lethal toxin-intoxicated murine macrophages. Furthermore,genes regulating growth and proliferation,transcription factor genes, and immune responsive genes were differentially expressed as a consequence of lethal toxin-mediated macrophage cytotoxicity.
Lee, Si-Beum,Nam, Kyung-Wan,Kim, Min-Soo,Jun, Seoung-Wook,Park, Jeong-Sook,Woo, Jong-Soo,Hwang, Sung-Joo The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.7
The objective of this study was to elucidate the feasibility to improve the solubility and bioavailability of poorly water-soluble itraconazole via solid dispersions by using supercritical fluid (SCF). Solid dispersions of itraconazole with hydrophilic polymer, HPMC 2910, were prepared by the aerosol solvent extraction system (ASES) under different process conditions of temperature/pressure. The particle size of solid dispersions ranged from 100 to 500 nm. The equilibrium solubility increased with decrease (15 to 10 MPa) in pressure and increase (40 to $60^{\circ}C$) in temperature. The solid dispersions prepared at $60^{\circ}C$/15 MPa showed a slight increase in equilibrium solubility (approximately 27-fold increase) when compared to pure itraconazole, while those prepared at $60^{\circ}C$/10MPa showed approximately 610-fold increase and no endothermic peaks corresponding to pure itraconazole were observed, indicating that itraconazole might be molecularly dispersed in HPMC 2910 in the amorphous form. The amorphous state of itraconazole was confirmed by DSC/XRD data. The pharmacokinetic parameters of the ASES-processed solid dispersions, such as $T_{max},\;C_{max},\;and\;AUC_{0-24h}$ were almost similar to $Sporanox_{\circledR}$ capsule which shows high bioavailability. Hence, it was concluded that the ASES process could be a promising technique to reduce particle size and/or prepare amorphous solid dispersion of drugs in order to improve the solubility and bioavailability of poorly water-soluble drugs.
Sibeum Lee,Kyungwan Nam,김민수,Seoung Wook Jun,박정숙,우종수,Sung-Joo Hwang 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.7
The objective of this study was to elucidate the feasibility to improve the solubility and bioavailability of poorly water-soluble itraconazole via solid dispersions by using supercritical fluid (SCF). Solid dispersions of itraconazole with hydrophilic polymer, HPMC 2910, were prepared by the aerosol solvent extraction system (ASES) under different process conditions of temperature/ pressure. The particle size of solid dispersions ranged from 100 to 500 nm. The equilibrium solubility increased with decrease (15 to 10 MPa) in pressure and increase (40 to 60oC) in temperature. The solid dispersions prepared at 45oC/15 MPa showed a slight increase in equilibrium solubility (approximately 27-fold increase) when compared to pure itraconazole, while those prepared at 60oC/10 MPa showed approximately 610-fold increase and no endothermic peaks corresponding to pure itraconazole were observed, indicating that itraconazole might be molecularly dispersed in HPMC 2910 in the amorphous form. The amorphous state of itraconazole was confirmed by DSC/XRD data. The pharmacokinetic parameters of the ASES-processed solid dispersions, such as Tmax, Cmax, and AUC0-24h were almost similar to Sporanox capsule which shows high bioavailability. Hence, it was concluded that the ASES process could be a promising technique to reduce particle size and/or prepare amorphous solid dispersion of drugs in order to improve the solubility and bioavailability of poorly water-soluble drugs.
이영,송규상,남재만,전은석,김선영,이복희,성인환,이경주 대한내과학회 1988 대한내과학회지 Vol.35 No.5
A case of a 58-year-old man with malignant fibrous histiocytoma (NFH) of the right ventricle is presented and the 9 previous reports of this rare cardiac tumor are reviewed. The chest PA showed cardiomegaly and small nodular densities in the right lower lung field. There were multiple perfusion defects in the right lung an perfusion lung scan. On echocardiogram, dilated right atrium and ventricle, mass on RVOT, tricuspid regurgitation and moderate pericardial effusion were noted. No lesions were noted in the liver, kidney, spleen, or pancreas on ultrasound. The microscopic view of the tumor showed a storiform pattern of fibroblasts, histiocytes, multinuclear giant cells and inflammatory cells. The patient died during open heart surgery for tumor resection.
Hong, Seong-Bin,Uhm, Wook-Hyun,Joo, Woo-Chul,Nam, Moon-Suk,Lee, Seoung-Woo,Song, Joon-Ho The Korean Society of Toxicogenomics and Toxicopro 2010 Molecular & cellular toxicology Vol.6 No.2
Alpha-lipoic acid (ALA) is a natural antioxidant that scavenges reactive oxygen species (ROS) and regenerates endogenous antioxidants. In the present study, plasma molecular markers of oxidative stress, inflammatory state, and endothelial cell injury was measured to investigate the effect of simultaneous blocking of both angiotensin (AT) II-and oxidative stress-mediated pathophysiologic pathways during the course of type II diabetic nephropathy in the clinical settings. Sixty-three diabetic subjects have carried out either of 12-month treatment course of AT-II receptor blocker (ARB) alone, ALA alone, or combination of both. Plasma malondialdehyde (MDA) level, a marker for oxidative stress, increased in ARB alone group whereas reduced to significantly lower level in ALA+ARB combination group. Plasma hs-CRP level, an inflammatory marker, decreased significantly in ARB+ALA group. Plasma thrombomodulin (TM) level, a marker of endothelial cell injury, increased in both ARB and ALA group. Twenty-four hour urinary protein excretion, as a marker of renal injury, decreased in ARB and ARB+ALA group. Finally, renal function was reserved well in ARB+ALA group in compared to others. The combined administration of ALA and ARB additively attenuated or reduced plasma markers of oxidative stress, inflammation and endothelial cell injury for one year. It suggests that the benefits in attenuating atherogenic process and vascular injury retard the progression of renal dysfunction.
Fast terahertz reflection tomography using block-based compressed sensing.
Cho, Sang-Heum,Lee, Sang-Hun,Nam-Gung, Chan,Oh, Seoung-Jun,Son, Joo-Hiuk,Park, Hochong,Ahn, Chang-Beom Optical Society of America 2011 Optics express Vol.19 No.17
<P>In this paper, a new fast terahertz reflection tomography is proposed using block-based compressed sensing. Since measuring the time-domain signal on two-dimensional grid requires excessive time, reducing measurement time is highly demanding in terahertz tomography. The proposed technique directly reduces the number of sampling points in the spatial domain without modulation or transformation of the signal. Compressed sensing in spatial domain suggests a block-based reconstruction, which substantially reduces computational time without degrading the image quality. An overlap-average method is proposed to remove the block artifact in the block-based compressed sensing. Fast terahertz reflection tomography using the block-based compressed sensing is demonstrated with an integrated circuit and parched anchovy as examples. (C) 2011 Optical Society of America</P>
[ I - 123 ] IPT SPECt를 이용한 정상인과 파킨슨환자의 도파민 운반체의 영상화 및 단순화된 정량분석 방법들의 비교연구
문대혁(Dae Hyuk Moon),양승오(Seoung Oh Yang),이희경(Hee Kyung Lee),김희중(Hee Joung Kim),류진숙(Jin Sook Ryu),천준홍(Jun Hong Cheon),임주혁(Joo Hyuck Im),봉정균(Jung Kyun Bong),남기표(Ki Pyo Nam),권수일(Soo Il Kwon) 대한핵의학회 1996 핵의학 분자영상 Vol.30 No.3
N/A The purpose of this study was to compare the specific binding ratio method with model based methods in estimating the transporter parameter k3/k4 in normal controls and Parkinson's patients with [I-123]IPT SPECT and to evaluate the usefulness of [I-123]IPT SPECT. 6.5±1.1 mCi (239.0±40.3 MBq) of [123]IPT was intravenouly injected as a bolus into six normal controls(age:45±13) and seventeen patients(age:55±8) with Pakinson's disease(PD). The transporter parameter k3/k4 was derived using the Ichise's graphical method(Rv) and Lassen's area ratio method(RA) for the dynamic IPT SPECT data without blood samples. Then, the relationships between the transporter parameter Rv, RA and the ratio of (BG-OCC)/OCC at 115 minutes were evaluated by linear regression analysis. Rvs by Ichise's graphical method for NC and PD were 2.08±0.29 and 0.78±0.31, respectively. RAs by Lassen's area ratio method for NC and PD were 1.48±0.16 and 0.65±0.24, respectively. The correlation coefficients between (BG-OCC)/OCC and Rv, (BG-OCC)/OCC and RA, and RV, and RA were 0.93, 0.90, 0.99 and their corresponding slopes were 0.54, 0.34, and 0.65,respectively. The Rv and RA of NC were significantly higher than the ones of PD. That is, the k3/k4 Of NC was clearly separated from the one of PD. k3/k4 showed a good correlation with the ratio of (BG-OCC)/OCC. The results indicate that the noninvasive simplified quantitative methods may be useful to measure the transporter parameter k3/k4 and the specific binding ratio method can be used for quantitative studies of dopamine transporter with [I-123]IPT SPECT in humans brains.