• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.399-408
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• 2018

In this study, we examined the molecular and functional characterization of choline uptake in the human esophageal cancer cells. In addition, we examined the influence of various drugs on the transport of [$^3H$]choline, and explored the possible correlation between the inhibition of choline uptake and apoptotic cell death. We found that both choline transporter-like protein 1 (CTL1) and CTL2 mRNAs and proteins were highly expressed in esophageal cancer cell lines (KYSE series). CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. Choline uptake was saturable and mediated by a single transport system, which is both $Na^+$-independent and pH-dependent. Choline uptake and cell viability were inhibited by various cationic drugs. Furthermore, a correlation analysis of the potencies of 47 drugs for the inhibition of choline uptake and cell viability showed a strong correlation. Choline uptake inhibitors and choline deficiency each inhibited cell viability and increased caspase-3/7 activity. We conclude that extracellular choline is mainly transported via a CTL1. The functional inhibition of CTL1 by cationic drugs could promote apoptotic cell death. Furthermore, CTL2 may be involved in choline uptake in mitochondria, which is the rate-limiting step in S-adenosylmethionine (SAM) synthesis and DNA methylation. Identification of this CTL1- and CTL2-mediated choline transport system provides a potential new target for esophageal cancer therapy.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.17 no.1
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• pp.31-36
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• 2014

Purpose: Infliximab (IFX) is considered safe and effective for the treatment of ulcerative colitis (UC) in both adults and children. The aim of this study was to evaluate the short- and long-term clinical course of IFX in Korean children with UC. Methods: Pediatric patients with UC who had received IFX infusions between November 2007 and May 2013 at Samsung Medical Center were retrospectively investigated. The clinical efficacy of IFX treatment was evaluated at 8 weeks (short term) and 54 weeks (long term) after the initiation of IFX treatment using the Pediatric Ulcerative Colitis Activity Index (PUCAI). The degree of response to IFX treatment was defined as complete response (PUCAI score=0), partial response (decrement of PUCAI score${\geq}20$ points), and non-response (decrement of PUCAI score <20 points). Adverse events associated with IFX treatment were also investigated. Results: Eleven pediatric patients with moderate to severe UC had received IFX. The remission rate after IFX treatment was 46% (5/11) and 82% (9/11) at 8 weeks and 54 weeks after IFX treatment, respectively. All patients who were steroid-dependent before treatment with IFX achieved remission at 54 weeks and were able to stop treatment with corticosteroids, while all steroid-refractory patients failed to achieve remission at 54 weeks after treatment with IFX. Conclusion: Response to IFX treatment after 8 weeks may predict a favorable long-term response to IFX treatment in Korean pediatric UC patients.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.24 no.2
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• pp.169-181
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• 2014

Objectives: The purpose of this study was to obtain information regarding classification and health hazards that may result from a 13-week inhalation exposure to 2-methylpentane by Sprague-Dawley rats. Materials: The testing method was conducted in accordance with OECD guidelines for the testing of chemicals No. 413. The rats were divided into four groups(ten male and ten female rats in each group) and exposed to 0 ppm, 290 ppm, 1,160 ppm, 4,640 ppm 2-Methylpentane in each exposure chamber for six hours per day, five days per week, for 13 weeks. Results: No death or particular clinical presentation including weight change and change of feed rate was observed. The relationships between dose, gender and response were also not significantly changed in urinalysis, hematologic examination, or biochemical examination of blood(except for total cholesterol being up, total protein being up, and chloride ion being down in males), and blood coagulation time. For the relative weight measurement of organs, in the male group the weight change of both kidney and liver were increased in proportion to dose. In histopathological examination, nephropathy in the kidney(cystic change of renal tubules, regenerative tubule, inflammatory cell infiltration and necrosis in the interstitial tissue) was increased in a dose-dependent manner in the male group(290 ppm, 1,160 ppm, 4,640 ppm). However, other organs were not affected by the test substance. Conclusions: 2-methylpentane was estimated as a chemical causing nephropathy in the male group. NOAEL(No Observable Adverse Effect Level) in the female group is more than 4,640 ppm, while inthe male group it is less than 290 ppm.

• Korean Journal of Soil Science and Fertilizer
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• v.45 no.4
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• pp.565-571
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• 2012

This study was conducted to investigate the tolerance of some resistant fungal strains from soils contaminated with heavy metals. Various fungal strains were isolated from soil samples collected from studied sites which heavy metals and other pollutants have been emitted in effluents for several years. Fungi isolated belong to different genera; however, Penicillium spp. showed the most frequent species. The microbial number was remarkably higher in the control soil than contaminated soil samples collected from mining areas. $Pb^{2+}$ and $Zn^{2+}$ had the highest concentration in the polluted soils ranging from 89 - 3,521 ppm and 98 - 4,383 ppm, respectively. The minimum inhibition concentrations (MICs) of $Pb^{+2}$ and $Zn^{+2}$ showed the highest values against the fungal strains. $Ni^{+2}$ and $Co^{+2}$ were the lowest contaminants in the polluted soils with the concentration of 5 to 12.1 ppm and 1.8 to 4.8 ppm, respectively. The tested resistant strains showed the strongest inhibition for $Ni^{+2}$ and $Co^{+2}$ up to 200-400 ppm. Cadmium was the most highly toxic heavy metal for most of strains, however, 1 mM of $Cr^{3+}$, $Cu^{2+}$ and $Pb^{2+}$ accelerated the growth of Penicillium verrucosum KNU3. $Cu^{+2}$ and $Zn^{+2}$ at concentration of 1 mM did not affect the growth rate P. funiculosum KNU4. Tolerance of fungal species to heavy metals appears to be strain and origin dependent.

• The Journal of Korean Society of Virology
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• v.28 no.4
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• pp.369-375
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• 1998

In our preliminary study to find antiviral or antitumor agents from Korean natural products, we found that the Shope fibroma virus (SFV) induced fibromas reaching maximum size at $5{\sim}6$ days with spontaneous disappearance at $15{\sim}20$ days after SFV intracutaneous inoculation into Korean domestic rabbits. However, the sizes of fibromas of rabbits at day 5 after virus inoculation were significantly different individually. Assuming that the variation of tumor size was due to either susceptibility or the preexisting antibodies against SFV in the Korean domestic rabbits, the rabbits were checked for the antibodies against SFV by IFAT using SFV infected RK13 cells. The antibody positive rate of normal Korean domestic rabbits was 32.8% and the sizes of the fibromas of the positive rabbits were significantly smaller than those of negative rabbits (p<0.0001). The fibroma sizes were dependent on the antibody titers of rabbits to SFV. The sizes of fibromas after inoculation of SFV into immunized rabbits were about one tenth of those by the first inoculation into normal rabbits. This is the first report on the antibody prevalence against SFV among normal Korean domestic rabbits and it suggest the existence of a wild fibroma virus or related virus in Korea.

• Journal of Microbiology and Biotechnology
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• v.14 no.6
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• pp.1286-1294
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• 2004

In a previous study by the current authors, hepatocellular carcinoma (HCC) was determined to be epidemiologically sex-dependent, and the incidence and multiplicity of HCC found to decrease in estradiol-3 benzoate (EB)-treated F344 rats. Therefore, to ascertain the anticancer mechanism of EB, a commercially available cDNA microarray, with a total of 14,815 cDNA rat gene clones, was used to determine the differentially expressed genes in nontreated livers, EB-treated livers, and diethynitrosolamine (DEN)-induced HCC. In the sequenced experiment, a total of 85 genes were differentially expressed at either two or more times the rate of the normal expression, where 33 genes were downregulated by EB, and 52 genes upregulated. Candidate genes were selected according to significant changes observed in the mRNA expression in the EB-treated livers compared with the nontreated livers, then these genes were filtered according to their different expression patterns in the DEN-induced tumors compared to the estrogen-treated livers. To confirm the microarray data, a real-time PCR analysis was performed for ten selected genes: the H-ras revertant protein 107 (H­rev107), insulin-like growth factor binding protein (lOFBP), parathyroid hormone receptor (PI'HR), SH3 domain binding protein (SH3BP), metallothionein, src-suppressed C-kinase substrate (SSeCK) gene, phosphodiesterase I, CD44, epithelial membrane protein 3 (EMP3), and estrogen receptor a (ERa). The SSeCK and phosphodiesterase I genes were both upregulated in the DEN-induced hepatocarcinomas, yet their possible carcinogenic functions remain unknown. Meanwhile, the other genes were downregulated, including the genes related to growth regulation (IOFBP, H-revI07, ER$\alpha$), adipogenesis inhibition (PTHR), and tumor suppression (metallothionein).

• Journal of Pharmacopuncture
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• v.13 no.3
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• pp.5-13
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• 2010

Reactive Oxygen Species(ROS) are continuously produced at a high rate as a by-product of aerobic metabolism. Since tissue damage by free radical increases with age, the reactive oxygen species(ROS) such as hydrogen peroxide($H_2O_2$), nitric oxide(NO). Several lines of evidence provided that ROS appears to cause to develop aging-related various diseases such as cancer, arthritis, cardiovascular disease. Our reserch objective was to examine the in vitro biological activity of Scolopendrid Pharmacopuncture, including the total poly-phenol content, DPPH radical scavenging, ABTS radical scavenging, Superoxide dismutase(SOD)-like activity, Nitrite scavenging ability. The total poly-phenol contents of Scolopendrid Pharmacopuncture was 35.859mg/L. Elctron donation ability on DPPH was 36.82%. The 2,2'-azinobis-3-ehtlbezothiazoline-6-sulfonic acid radical decolorization (ABTS) was 84.7%. The superoxide dismutase (SOD)-like activities of Scolopendrid Pharmacopuncture was 44.33%. The nitrite scavenging effects were pH dependent, and were highest at pH 1.5(45.2%) and lowest at pH 6.0(11.3%). We conclude that Scolopendrid Pharmacopuncture may be useful as potential sources of antioxidant.

• Journal of Pharmaceutical Investigation
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• v.27 no.4
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• pp.313-321
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• 1997

Ion exchange resin complexes of famotidine have been prepared by the reaction of famotidine solution with activated ion exchange resins. Complex formation efficiency between famotidine and ion exchange resin was about $80{\sim}90%$ in average, calculated by HPLC determination. Drug release characteristics from the resin complexes were evaluated by the modified percolation method. Famotidine release was dependent on the type of ion exchange resins. In the case of weakly acidic resin complexes, the cumulative released amount of famotidine was more than 90% for 1hr in pH 1.2 buffer solution. However, in the case of strongly acidic resin complexes, it was less than 5% for 3hr in the same medium. Strongly acidic resins revealed some advantages over weakly, acidic resins for overcoming instability of famotidine in gastric juice. In addition, strongly acidic resin complexes showed controlled release of famotidine in pH 6.8 buffer solution, showing the result of about 60 to 70% of drug release for 5hr. After oral administrations of famotidine-resin complexes to rats as dose of 40 mg equivalent/kg, the pharmacokinetic parameters of famotidine were obtained by model independent analysis and compared with those of famotidine solution or suspension. $C_{max}$ of famotidine-resin complex was lower than that of famotidine solution or suspension. MRT, MAT, and MDT of the complexes were greater than those of famotidine solution or suspension. From these results, it was expected that famotidine was released slowly from the complexes and absorbed continuously into systemic circulation. It was recognized that drug release from the complexes was the rate-limiting step in drug absorption, since there were close correlations between in vitro drug release and in vivo pharmacokinetic parameters.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.61-61
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• 2003

We have investigated the novel function of tissue transglutaminase (tTG) in the germinal vesicle breakdown (GVBD) of mouse oocyte. tTG was identified in ooplasm and germinal vesicle by immunostaining assay. Spontaneous maturation of the oocytes elevated in situ activity of tTG by over 2.5 fold at 3 hr, which was determined by a confocal microscopic assay. However, incubation with monodansylcadaverine (MDC), a tTG inhibitor, blocked the activation of tTG. The possible role of tTG in GVBD was investigated by the use of two tTG inhibitors, MDC and cystamine. MDC largely inhibited the GVBD by a concentration dependent manner. GV-stage oocytes were matured to the GVBD stage by 78% at 3 hr in BWW culture medium. However, in the oocytes incubated with MDC for 3 hr, the GVBD rates were 43 and 11% by 50 and 100 mM, respectively. MDC also blocked the entry of 70 kDa TRITC-dextran from the ooplasm to the compartment of germinal vesicle, indicating a possible inhibition of nuclear pore disassembly by MDC. The role of tTG in GVBD was further investigated by microinjection with cystamine. The control oocytes, injected with DPBS, showed about 80 % of GVBD at 3 hr. But the oocytes injected with cystamine showed 15% of GVBD at 3 hr and a little higher rate at 6 hr. In addition, the inhibition of GVBD maturation by MDC was reversible by washing. These results suggested that tTG was involved in the early event of mouse oocyte maturation

• Journal of Energy Engineering
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• v.7 no.2
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• pp.202-208
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• 1998

As in the other industrial processes, a nuclear power plant involves a steam relieving process through which condensable steam is discharged and condensed in a subcooled pool. An analysis of steam discharge transients was carried out using the method of characteristics to determine the flow characteristics and dynamic loads of piping that are used for structural design of the piping and its supports. The analysis included not only the steam flow rate but also the flow rates of the air and water which originally exist in the pipe. The analytical model was developed for a uniform pipe with friction through which the flow was discharged into a suppression pool. Including the combinations of system elements such as reservoir, valve and branching pipe lines. The piping flow characteristics and dynamic loads were calculated by varying system pressure, pipe length, and submergence depth. It was found that the dynamic load, water clearing time and water clearing velocity at the water/air interface were dependent not only on the system pressure and temperature but also on the pipe length and submergence depth.