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13 weeks repeated oral dose toxicity studies with LMK02-Jangwonhwan in SD rats (LMK02의 Sprague-Dawley 랫드를 이용한 13 주간 반복 경구투여 독성시험)

  • Kang, Hyung-Won;Jang, Hyun-Ho;Park, Jang-Ho;Kim, Tae-Heon;Lyu, Yeoung-Su
    • Journal of Oriental Neuropsychiatry
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    • v.23 no.2
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    • pp.99-120
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    • 2012
  • Objectives : The oriental medicine Jangwonhwan, a boiled extract of 12 medicinal herbs/mushrooms, has been prescribed to patients with cognitive dysfunction, as originally described in the Korean medical text, DonguiBogam(amnesia chapter). Recently, a modified formula of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushrooms, was shown to reduce the ${\beta}$-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model for Alzheimer's disease. The toxicity of LMK02-Jangwonhwan was investigated in SD rats, by a daily oral administration for 13 weeks and NOAEL(No observed adverse effect dose), a definite toxic dose and target organ, as well. Methods : Quality control of the tablet form of LMK02-Jangwonhwan was established by estimating the indicative components, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelicagigas Nakai. The toxicity of LMK02-Jangwonhwan was investigated in 6 week old, specific pathogen free (SPF), Sprageu-Dawley rats by oral administration. Each test group consisted of 10 male and 10 female rats. The groups received doses of 500, 1,000 or 2,000 mg/kg/day of test substance for 13 weeks. The clinical signs, death rate, body weight, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemistry, organ weight and pathological changes were examined and compared with those of the control group. Results : The 13-week repeated oral treatment doses didn't result in any specific symptoms or death. There were no significant changes in the rat's weight and food consumption. Further, ophthalmic examination, urinalysis, hematological, serum biochemistry test and organ weight revealed no significant differences. Conclusions : The no-observed-adverse-effect level(NOAEL) of LMK02 for male and female Sprague-Dawley rats was determined as 2,000mg/kg/day and the target organ wasn't confirmed. Because no significant adverse effects were observed, the target organ could not be determined.

Biosynthesis of Lactate-containing Polyhydroxyalkanoates in Recombinant Escherichia coli from Sucrose (재조합 대장균에서 수크로즈로부터의 젖산을 모노머로 함유한 폴리하이드록시알칸산 생산 연구)

  • Oh, Young Hoon;Kang, Kyoung-Hee;Shin, Jihoon;Song, Bong Keun;Lee, Seung Hwan;Lee, Sang Yup;Park, Si Jae
    • KSBB Journal
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    • v.29 no.6
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    • pp.443-447
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    • 2014
  • Biosynthesis of lactate-containing polyhydroxyalkanoates (PHAs) was examined in recombinant Escherichia coli W strain from sucrose. The Pseudomonas sp. MBEL 6-19 phaC1437 gene and the Clostridium propionicum pct540 gene, which encode engineered Pseudomonas sp. MBEL 6-19 PHA synthase 1 ($PhaC1_{Ps6-19}$) and engineered C. propionicum propionyl-CoA transferase ($Pct_{Cp}$), respectively, were expressed in E. coli W to construct key metabolic pathway to produce poly(3-hydroxybutyrate-co-lactate) [P(3HB-co-LA)]. The recombinant E. coli W expressing the phaC1437 gene and the pct540 gene could synthesize P(3HB-co-13mol%LA) up to the polymer content of 31.3 wt% when it was cultured in chemically defined MR medium containing 20 g/L of sucrose and 2 g/L of sodium 3-hydroxybutyrate. When Ralstonia eutropha phaAB genes were additionally expressed to provide 3-hydroxybutyrate-CoA (3HB-CoA) from sucrose, P(3HB-co-16mol%LA) could be synthesized from sucrose as a sole carbon source without supplement of sodium 3-hydroxybutyrate in culture medium, but the PHA content was decreased to 12.2 wt%. The molecular weight of P(3HB-co-16 mol%LA) synthesized in E. coli W using sucrose as carbon source were $1.53{\times}10^4$ ($M_n$) and $2.78{\times}10^4$ ($M_w$), respectively, which are not different from those that have previously been reported by other recombinant E. coli strains. Engineered E. coli strains developed in this study should be useful for the production of lactate-containing PHAs from sucrose, one of the most abundant and least expensive carbon sources.

A Study on the morphologic characteristics of each constitution's trunk (체간부의 사상체질별 형태학적 특징에 관한 연구)

  • Hong, Suck-chull;Lee, Su-kyung;Lee, Eui-joo;Han, Gi-hwan;Chou, Yong-jin;Choi, Chang-seok;Koh, Byung-hee;Song, Il-byung
    • Journal of Sasang Constitutional Medicine
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    • v.10 no.1
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    • pp.101-142
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    • 1998
  • 1. Objects The base of classification of Sasang Constitution was the different congenital formation of organs such as lungs, spleen, liver, kidneys, and it was expanded from the viscera region of lungs, spleen, liver, kidneys to the body shape of trunk. The researched about body shape of Sasang Constitution have had points of issues which derived by measurement with hands. But this study was measured the characteristics of body shape putting in importance of anatomical position with the computerized 3-Dimension scanner, which minimized the errors of measurement, and it was abled the cubic measurement such as volume, area of cross section as well as round length. 2. Materials & Method The examinee was healthy male 40 persons and female 20 persons from 20's to 40's, who was diagnosed by the specialist of Sasang Constitutional Medicine. The body shape was measured round length, area of cross section, and volume of 31 anatomical points and the 25 hypothesis with the Rapid 3D Color Scanner Model 3030 RGB/PS. And the characteristics of each constitution's body shape was derived. 3. Results & Concousion In female, Taeumin had the largest trunk and Soeumin had the smallest trunk compared to other constitution, but Soyangin had only the smallest neck. Soeumin has the smallest round length of nipple and the $CV_{12}$, and Soyangin has the smallest breadth of ASIS. Soyangin had the smallest volume from thyroid bone to the highest points of armpits and from sternum to nipple. Taeumin had the largest volume from sternum to the $CV_{12}$ and from sternum to xiphoid process. In male, Taeumin had the largest trunk and Soeumin had the smallest trunk from the level of thyroid bone to ASIS. Soyangin has the longest distance and Soeumin has the shortest distance from nipple to the lowest of breast. Taeumin had the largest volume of trunk and Soeumin had the smallest volume of trunk. In the ration of four-Cho, Taeumin had the longest distance from the highest points of armpits to nipple and Soyangin had the shortest distance of that. Soyangin had the smallest ratio of the height of upper middle cho. Soeumin had the smallest ratio from the $CV_{12}$ to navel among trunk. In the correlation among the four Cho, Taeumin had the negative correlation between the Upper-Cho and the Lower-Middle-Cho significantly.

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The Properties of Hole Injection and Transport Layers on Polymer Light Emitting Diode (정공 주입층 및 수송층에 따른 고분자 유기발광다이오드의 특성 연구)

  • Shin, Sang-Baie;Chang, Ho-Jung
    • Journal of the Microelectronics and Packaging Society
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    • v.14 no.4
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    • pp.37-42
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    • 2007
  • We fabricated the polymer light emitting diodes (PLEDs) with ITO/PEDOT:PSS/PVK/PFO:MEH-PPV/LiF/Al structures. The effect of the thickness of PEDOT:PSS hole injection layer(HIL) on the electrical and optical properties of PLEDs was investigated. In addition, PVK hole transport layer(HTL) was introduced in the PLED device, and compared the properties of the PLEDS with and without PVX layer. All organic film layers were prepared by the spin coating method on the plasma treated ITO/glass substrates. As the thickness of PEDOT:PSS film layer decreased from about 80 nm to 50 nm, the luminance of PLED device increased from $220cd/m^2$에서 $450cd/m^2$. This may be ascribed to the increased transportation efficiency of the holes into the emission layer of PLED. The maximum current density and luminance were obtained fir the PLED device with PVX hole transport layer, showing that the current density and luminance were $268mA/cm^2\;and\;540cd/m^2$ at 12V, respectively. This values were improved by about 14% and 22% in current density and luminance compared with the PLED device without PVK layer.

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Adverse Reproductive Effects on Plasma Vitellogenin and Sex Steroid Levels, and Gonadosomatic Index in Juvenile Common Carps (Cyprinus carpio) Exposed to 17$\beta$-Estradiol and D-2-Ethylhexyl Phthalate

  • Seo, Jinwon;Park, Kyung-Seo;Moon, Woon-Gi;Lee, Sung-Kyu
    • Proceedings of the Korea Society of Environmental Biology Conference
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    • 2002.11a
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    • pp.141-144
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    • 2002
  • Environmental estrogens are natural or synthetic substances present in the aquatic environment, especially in effluent from sewage treatment. However, the adverse effects of these estrogenic substances on fish reproduction are unknown. Di-2-ethylhexyl phthalate (DEHP) is the most common phthalate, which Ps used as a plasticizer in polyvinylchloride (PVC), and it is widespread in the environment and has been found in aquatic organisms and sediments. Therefore, juvenile common carps (Cyprinus carpio) were exposed to nominal concentrations of 17$\beta$-estradiol (E2) (0.5, 5, 50 $\mu\textrm{g}$/L) and DEHP (10, 100, 500 $\mu\textrm{g}$/L) for 21 days, to determine the adverse reproductive effects of these compounds on plasma vitellogenin (VTG) induction, sex steroid level, and gonad weight. Electrophoresis (SDS-PAGE) revealed that much of VTG was induced in fish exposed to 5 and 50 E$_2$ $\mu\textrm{g}$/L, but none of DEHP exposure showed induction. Enzyme-linked immunosorbent assay (ELISA) revealed that VTG was significantly induced in fish exposed to 5 and 50 E$_2$ $\mu\textrm{g}$/L, and combination of 50 E$_2$ $\mu\textrm{g}$/L with 10 and 500 DEHP $\mu\textrm{g}$/L, but none of DEHP exposure showed induction. Analysis of sex steroid levels in some fish revealed that testosterone (T) was detected in both male and female fish of the control and DEHP exposures, but none of fish exposed to 22 concentrations had detectable testosterone level. On the other hand, E$_2$ exposure induced 17$\beta$-estradiol in plasma of male fish, but there was no induction of 17$\beta$-estradiol in plasma of male fish exposed to DEHP. Comparison of gonadosomatic index (GSI) revealed that maximal E$_2$ exposure inhibited ovarian growth, but maximal DEHP exposure stimulated testicular growth. The results indicated that those comparisons can be a useful bio-indicator for determining adverse reproductive effect of endocrine disrupting chemicals (EDCs).

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Enzymatic synthesis of structured lipids containing conjugated linolenic acids extracted from pomegranate seed oil and their physicochemical characteristics (석류 종자유로부터 얻어진 Conjugated Linolenic Acid를 함유한 기능성 고체지의 효소적 합성 및 이화학적 특성 연구)

  • Lee, Koo;Shin, Jung-Ah;Lee, Ki-Teak
    • Korean Journal of Agricultural Science
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    • v.39 no.3
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    • pp.395-405
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    • 2012
  • Lipozyme TL IM-catalyzed esterification was carried out to produce functional hard fat (structured lipid, SL) using palm stearin (PS) and hydrolysate of pomegranate seed oil (HPSO) of 1:6 molar ratio. HPSO contained conjugated linolenic acid (CLnA, about 80%). The reaction was performed at non-solvent system and solvent (n-hexane) system using Lipozyme TL IM (10% of total substrates, w/w) for 12, 24, and 72 hr in a shaking water bath ($55^{\circ}C$ and 185 rpm), respectively. SL synthesized in non-solvent system (NH-SL) and SL synthesized in n-hexane system (H-SL) were refined after deacidification, respectively. Their physicochemical properties were compared to obtain desirable functional hard fat. The content of CLnA in NH-SL increased from 34.38% to 40.63% with increasing reaction time. Similar results also observed in H-SL resulting in 36.81~45.83% of CLnA. In triacylglycerol (TAG) composition, the main molecules of LnLnLn (Ln=linolenic acid, PN=36) and the LnLnP (P=palmitic acid, PN=40) were newly synthesized in NH-SL and H-SL with increasing reaction time. After 72 hr reaction, iodine values of NH-SL (136.49) and H-SL (140.37) showed high values because of the high content of CLnA. Solid fat index (SFI) in NH-SL was higher than that in H-SL at each measured temperature. The predominant polymorphic forms of NH-SL and H-SL obtained after esterification for 72 hr were the desirable crystalline structure of the ${\beta}$' form.

Comparative analysis on mechanical properties of gold and Co-Cr dental alloys due to joining methods (이종금속간의 결합방법에 따른 결합강도에 관한 비교 연구)

  • Park, Seong-Kyu;Choi, Boo-Byung;Kwon, Kung-Rock
    • Journal of Dental Rehabilitation and Applied Science
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    • v.19 no.2
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    • pp.75-86
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    • 2003
  • The purpose of this study was to evaluate their mechanical properties after laser-welding or soldering of precious and non-precious dental alloys. For this study, 30 Co-Cr alloy specimens, 15 gold alloy specimens, 15 palladium alloy specimens were casted and seperated on the middle area. 15 sperated Co-Cr specimens and 15 seperated gold alloy specimens were laser welded (GW Group). 15 sperated Co-Cr specimens and 15 sperated gold alloy specimens were soldered by coventional soldering method (GS Group). 15 sperated Co-Cr specimens and 15 seperated palladium alloy specimens were laser welded (PW Group). 15 sperated Co-Cr specimens and 15 sperated palladium alloy specimens were soldered by coventional soldering method (PS Group). Tensile strength, 0.2% yield strength, % elongation were recorded in nine specimens of each group. Bending strength were record in six specimens of each group. These data for four groups were subjected to a two-way analysis of variance(ANOVA). The fracture locations, fractured surfaces were examined by SEM(scanning electron microscope). The results were as following: 1) In the same alloy combination, the tensile strength and 0.2% yield strength and of the laser welded group with same metal combination were significantly less than soldered groups(p<0.05). 2) In the combination of Co-Cr/Palladium, the bending strength of laser welded group were significantly less than that of soldered groups(p<0.05). In the combination of Co-Cr/Gold, the bending strength of laser welded group were significantly higher than that of soldered groups(p<0.05). 3) In the same method of joint, the tensile strength and 0.2% yield strength and bending strength of the Co-Cr/gold were significantly higher than Co-Cr/palladium(p<0.05). 4) There was no significantly statistical difference between each group in the % elongation(p>0.05). 5) The fracture of the laser welded specimens occured in the welding area and a large void was observed at the center of the fracture surface. 6) The fracture of the soldered specimens occured also inthe soldered area and many porpsities were showed at the fracture sites.

EGFR Mutation Genotype Impact on the Efficacy of Pemetrexed in Patients with Non-squamous Non-small Cell Lung Cancer

  • Igawa, Satoshi;Sato, Yuichi;Ishihara, Mikiko;Kasajima, Masashi;Kusuhara, Seiichiro;Nakahara, Yoshiro;Otani, Sakiko;Fukui, Tomoya;Katagiri, Masato;Sasaki, Jiichiro;Masuda, Noriyuki
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3249-3253
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    • 2016
  • Background: Pemetrexed monotherapy has come to be recognized as one of the standard second-line therapies for advanced non-squamous non-small cell lung cancer (NSCLC). However, there have been no reports of studies that have evaluated the efficacy of pemetrexed according to type of active EGFR mutation, i.e., an exon 19 deletion or an L858R point mutation. Materials and Methods: The records of non-squamous NSCLC patients harboring an EGFR mutation who received pemetrexed monotherapy as a second or later line of chemotherapy at Kitasato University Hospital between March 2010 and October 2015 were retrospectively reviewed, and the treatment outcomes were evaluated. Results: The overall response rate and progression-free survival time (PFS) of the 53 patients with non-squamous NSCLC were 15.1% and 2.3 months, respectively. There were significant differences between the disease control rate (37.5% vs. 76.2%) and PFS time (1.8 months vs. 3.3 months) of the exon 19 deletion group and the L858R point mutation group, and a multivariate analysis identified type of EGFR mutation as well as performance status (PS) as independent predictors of PFS. Conclusions: The clinical data obtained in this study provided a valuable rationale for considering type of EGFR mutation as well as non-squamous histology as predictors of the efficacy of pemetrexed monotherapy.

Study of Jindo Dog Personality Traits:Questionnaire of The 16th Korean Jindo Dog Show (진도개 성격형질연구:제16회 한국진도개품평회 설문조사)

  • Hong, Kyung-Won;Kim, Young-San;Shin, Young-Bin;Oh, Seok-Il;Kim, Jong-Seok;Choi, Hyuk;Lee, Ji-Woong;Sun, Sang-Soo;Lee, Jae-Il;Lee, Sang-Eun;Chung, Dong-Hee;Cho, Yong-Min;Im, Seok-Ki;Choi, Bong-Hwan
    • Journal of Animal Science and Technology
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    • v.50 no.2
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    • pp.273-278
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    • 2008
  • There have been studies about dog’s personality and behavior, which is helpful to breed dogs as guide or companion. In this study, a questionnaire was developed using 54 Jindo dogs, which considered ten items about aggressiveness and sociability. The scores were analyzed by principle component analysis (PCA), after accounting for four variables: age, gender, growing place, and coat-colors. Our results from the PCA indicated three principle components, which classified ‘aggressiveness’, ‘sociability’ and unknown factor. The four variables did not significantly affect aggressiveness(P>0.05). However, there was a relationship between coat-color and sociability, i.e., the Jindo dogs with fawn color were more sociable than the white ones(P<0.1).

Biosynthesis of Lactate-containing Polyhydroxyalkanoates in Recombinant Escherichia coli by Employing New CoA Transferases (재조합 대장균에서 새로운 코엔자임 에이 트랜스퍼레이즈를 이용한 젖산을 모노머로 함유한 폴리하이드록시알칸산 생산 연구)

  • Kim, You Jin;Chae, Cheol Gi;Kang, Kyoung Hee;Oh, Young Hoon;Joo, Jeong Chan;Song, Bong Keun;Lee, Sang Yup;Park, Si Jae
    • KSBB Journal
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    • v.31 no.1
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    • pp.27-32
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    • 2016
  • Several CoA transferases from Clostridium beijerinckii, C. perfringens and Klebsiella pneumoniae were examined for biosynthesis of lactate-containing polyhydroxyalkanoates (PHAs) in recombinant Escherichia coli XL1-Blue strain. The CB3819 gene and the CB4543 gene from C. beijerinckii, the pct gene from C. perfringens and the pct gene from K. pneumoniae, which encodes putative CoA transferase gene, respectively, was co-expressed with the Pseudomonas sp. MBEL 6-19 phaC1437 gene encoding engineered Pseudomonas sp. MBEL 6-19 PHA synthase 1 ($PhaC1_{Ps6-19}$) to examine its activity for the construction of key metabolic pathway to produce poly(3-hydroxybutyrate-co-lactate) [P(3HB-co-LA)]. The recombinant E. coli XL1-Blue expressing the phaC1437 gene and CB3819 gene synthesized poly(3-hydroxybutyrate) [P(3HB)] homopolymer to the P(3HB) content of 60.5 wt% when it was cultured in a chemically defined medium containing 20 g/L of glucose and 2 g/L of sodium 3-hydroxybutyrate. Expression of the phaC1437 gene and CB4543 gene in recombinant E. coli XL1-Blue also produced P(3HB) homopolymer to the P(3HB) content of 51.2 wt% in the same culture condition. Expression of the phaC1437 gene and the K. pneumoniae pct gene in recombinant E. coli XL1-Blue could not result in the production of PHAs in the same culture condition. However, the recombinant E. coli XL1-Blue expressing the phaC1437 gene and the C. perfringens gene could produce poly(3-hydroxybutyrate-co-lactate [P(86.4mol%3HB-co-13.7 mol%LA) up to the PHA content of 10.6 wt% in the same culture condition. Newly examined CoA transfereases in this study may be useful for the construction of engineered E. coli strains to produce PHA containing novel monomer such lactate.