• Title/Summary/Keyword: Lead compound

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Metabolic Engineering of the Brassinosteroid Biosynthetic Pathways (Brassinosteroid의 대사공학)

  • LEE Mi-Ock;SONG Ki-Hong;LEE Hyun-Kyung;JUNG Ji-Yoon;CHOE Vit-Nary;CHOE Sunghw
    • Proceedings of the Korean Society of Plant Biotechnology Conference
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    • 2002.04a
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    • pp.69-75
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    • 2002
  • Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd/dwf3 were shown to be blocked in $D^4$ reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bri1/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus It is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRI1 could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

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Pharmacokinetic analysis for the development of new potent anti-HIV-1 agents, the KR-V series (새로운 항HIV-1제, KR-V series의 개발을 위한 약물동태연구)

  • Lee, Young-mi;Kim, Jin-suk;Han, Sang-seop;Shin, Ho-chul
    • Korean Journal of Veterinary Research
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    • v.40 no.3
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    • pp.471-478
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    • 2000
  • The pharmacokinetic properties of KR-V compounds, recently developed as new anti-HIV agents, were studied after i.v. and p.o. administration in rats. The concentrations of the KR-V series were determined in rat plasma using an high-performance liquid chromatography (HPLC)-UV detection system. Of the 19 KR-V compounds investigated in the present study, only KR-V 3, 10, 14, 16 and 18-1 showed oral bioavailability. The plasma concentration-time data could be adequately described by an one-compartment open model. In the i.v. kinetic study (10mg/kg), the CLt of KR-V 3, 10, 14 and 16 (>4L/hr/kg) were significantly higher than that of KR-V 18-1 (1.1 L/hr/kg). The AUC of KR-V 18-1 was greater ($8.97{\mu}g{\cdot}hr/ml$) than that of the other compounds, but the Vd (0.58 L/kg) was lower. In the p.o. kinetic study (50mg/kg), although the t-1/2 of KR-V 18-1 was shorter than that of the other compounds, the AUC ($3.659{\mu}g{\cdot}hr/ml)$ and $C_{max}(1.891{\mu}g/ml$) were markedly higher. In a seperated in vitro experiment, only KR-V 18-1, of the 5 compounds with bioavailibility, exhibits potent activity against HIV-1 mutant strains. Therefore, KR-V 18-1 is expected to become a new potent anti-AIDS drug candidate/lead compound.

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In vitro anti-cancer activity of hydrophobic fractions of Sparassis latifolia extract using AGS, A529, and HepG2 cell lines (꽃송이버섯(Sparassis latifolia) 추출물 소수성 분획의 항암 활성)

  • Choi, Moon-Hee;Han, Hyo-Kyung;Lee, Yong-Jo;Jo, Han-Gyo;Shin, Hyun-Jae
    • Journal of Mushroom
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    • v.12 no.4
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    • pp.304-310
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    • 2014
  • The use of mushrooms has immense potential in many diverse applications. Until now, more than 3,000 species are consumed around the world, and more than 100 have shown promising clinical activity against cancer and other chronic diseases. Sparassis latifolia (formerly S. crispa) is an edible mushroom that harbors ${\beta}$-glucan reported to possess immunostimulatory and anticancer properties. However there have been no reports on the anticancer activity of hydrophobic fractions of S. latifolia. In this study, the anticancer activities of S. latifolia extract and hydrophobic fractions were investigated using AGS (stomach cancer), A529 (lung cancer), and HepG2 (liver cancer) cell lines. In cytotoxicity results of A529 cells, fractions of A2, A3, A4, A6, A7, A8, A9, and A10 in all 12 fractions show low $IC_{50}$ values. For HepG2 cells, A7 fraction results in the lowest $IC_{50}$ value while A7, A8, and A11 fractions show low $IC_{50}$ values in AGS cells. S. latifolia extract lead to low cell viability in cancer cells, compared to positive control of paclitaxel. A compound with molecular weight of 181 were detected using HPLC-MS but not identified yet. As a result, the hydrophobic fractions of S. latifolia EtOH extract would be a possible candidate as natural anticancer agents in the future.

Effects of the cis-Dichlorodiammineplatinum on the Fine Structures of the Interalveolar Septum in the Mouse (cis-Dichlorodiammineplatinum (II) 이 생쥐 폐포간중격의 미세구조에 미치는 영향)

  • Baik, Tai-Kyeoung;Kwon, Ik-Seung;Kim, Won-Kyu;Baik, Doo-Jin;Chung, Ho-Sam;Lee, Kyu-Sik
    • Applied Microscopy
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    • v.23 no.1
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    • pp.35-55
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    • 1993
  • cis-Dichlorodiammineplatinum (II) (cis-Platin), a metallic compound, has widely been used as an effective anticancer chemotherapeutic agent. The precise mechanism of action of this agent is still unknown, but it is postulated that cis-Platin may act on the cancer cell like bifunctional alkylating agents. Although this agent is very beneficial to the patients with cervical cancer, germinoma of testis, neuroblastoma and others, it may also damage to the normal cell so that many side effects; severe hemorrhagic enterocolitis, bone marrow depression, renal damage and liver damage will develope. This experiment has been undertaken to pursue the cytotoxic effects of the cis-Platin on the ultrastructures of the interalveolar septum in the mouse lung. A total of 55 healthy male mice of ICR strain were used as experimental animals and divided into 5 mice of normal control group and 50 mice of cis-Platin treated group. The mice of cis-Platin treated group were sacrificed by carotid exsanguination at 6, 12, 24 hours, 3 days and 7 days after intraperitoneal injection of 6.0 mg of cis-Platin ($Abiplatin^R$ Abic Co. Ltd.) per kg of mouse body weight. The specimen obtained from the lower lobe of left lung were sliced into $1mm^3$ and prefixed with 2% glutaraldehyde -2.5% paraformaldehyde solution prepared with Millonig's phosphatae buffer solution (pH 7.4) at $4^{\circ}C$ for 3-4 hours. After postfixation with 1% osmium tetroxide solution all specimens were embedded in Epon 812. Ultrathin sections about $600-800{\AA}$ in thickness were stained with uranyl acetate and lead citrate and observed with Hitachi-600 electron microscope. The results obtained were as follows: 1. Local swellings with increase of electron density and number of pinocytic vesicles in the cytoplasms of the type I pneumocyte and endothelial cell of the blood air barrier in interalveolar septum of cis-platin treated mice were observed. 2. Cisternae of rough endoplasmic reticulum were dilated and sacculated in association with detachment of membrane bound ribosomes of the type II pneumocyte in interalveolar septum of cis-Platin treated mice. 3. Swollon mitochondria with uneven electron density of their matrix were observed in the type II pneumocyte of interalveolar septum in the cis-Platin treated mice. 4. The lamellae of lammelar bodies in type II pneumocyte of interalveolar septum in cis-Platin treated mice were devoided or transformed into homogeneous electron dense material. It is consequently suggested that cis-Platin would induce the cellular edema of type I pneumocyte and endothelial cell, and degenerative changes of cytoplasmic organelles of the type II pneumocyte in the interalveolar septum of the mouse lung.

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LB30057, an Orally Effective Direct Thrombin Inhibitor, Prevents Arterial and Venous Thrombosis in Rats and Dogs

  • Park, Hee-Dong;Kim, Hee-Jin;Oh, Yeong-Soo;Kim, In-Chull;Kim, Yong-Zu;Koh, Hyun-Chul;Shin, In-Chul;Lee, Yong-Hee;Lee, Chang-Ho
    • Archives of Pharmacal Research
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    • v.26 no.3
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    • pp.224-231
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    • 2003
  • The anti-thrombotic effects of LB30057, a direct thrombin inhibitor, were evaluated with in vivo rat and dog thrombosis models. In rats, 1 mg/kg of LB30057 inhibited half of the clot formations in the inferior vena cava at 5 minutes after intravenous application. When measured at 2 hours after oral application, 100 mg/kg prevented approximately half of the clot formations in the inferior vena cava and 50 mg/kg prolonged the mean occlusion time from $15.6{\pm}1.3$ minutes to $47.2{\pm}8.3$ minutes in the carotid artery. In dogs, the formation of thrombus in the jugular vein was reduced to half at a dose range of 20-30 mg/kg at 6 hours after oral application. In addition, the LB30057 dosage required to reduce venous clot formation by approximately 80-90% in dogs was only about 10% of that required for the same reduction in rats. This is probably due to the variation in its time-dependent blood concentration profiles in each species; for example, the plasma half-life of LB71350 in dogs was longer than that in rats ($153.0{\pm}3.0$ vs. $129.7{\pm}12.7$ min at 30 mg/kg, i.v., respectively). AUG, $T_{max},{\;}G_{max}$, and BA in dogs were 59, 8.9, 9.17, and 13.3 times higher than those in rats at oral 30 mg/kg, respectively. Taken together, these results suggest that LB30057 administered orally is effective in the prevention of arterial and venous thrombosis in rats and dogs. It therefore represents a good lead compound for investigations to discover a new, orally available, therapeutic agent for treating thrombotic diseases.

Mechanical Characteristic Evaluation of Sn-Ag-Cu Lead Free Solder Ball Joint on The Pad Geometry (패드 구조에 따른 Sn-Ag-Cu계 무연 솔더볼 접합부의 기계적 특성평가)

  • Jang, Im-Nam;Park, Jai-Hyun;Ahn, Yong-Sik
    • Journal of the Microelectronics and Packaging Society
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    • v.17 no.2
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    • pp.41-47
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    • 2010
  • The effect of PCB and BGA pad designs was investigated on the mechanical property of Pb-free solder joints. The mechanical property of solder joint was tested by three different test methods of drop impact tests, bending impact test, and high speed shear test. Two kinds of pad design such as NSMD (Non-Solder Mask Defined) and SMD (Solder Mask Defined) were applied with the OSP finished Pb-free solder (Sn-3.0Ag-0.5Cu, Sn-1.2Ag-0.5Cu). in the drop impact test and bending impact test, the characterized lifetime showed the same tendency, and SMD design showed better mechanical property of solder joint than NSMD regardless of test method, which was due to the different crack path. The fracture crack on SMD pad was propagated along the intermetallic compound (IMC) layer of solder joint, while the fracture crack on NSMD pad propagated through upper edge of land which shields pattern. In the high speed shear test, pad lift occurred on the solder joint of NSMD. SMD/SMD combination of pad design consequently illustrated the best mechanical property of BGA/PCB solder joint, followed by SMD/NSMD, NSMD/SMD, and NSMD/NSMD.

High-efficiency and Rapid Agrobacterium-mediated genetic transformation method using germinating rice seeds (벼 발아초기 종자를 이용한 고효율 단기형질전환 방법)

  • Lee, Hye-Jung;Abdula, Sailila E.;Jee, Moo-Geun;Jang, Dae-Won;Cho, Yong-Gu
    • Journal of Plant Biotechnology
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    • v.38 no.4
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    • pp.251-257
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    • 2011
  • Rice is the most important crop as a model plant for functional genomics of monocotyledons. Rice is usually transformed using Agrobacterium tumefaciens. However, the transformation efficiency using previous method is still low. In this study, we established a new method by modifying the general Agrobacterium protocol especially in the inoculation and co-cultivation step. We directly inoculated Agrobacterium containing a CIPK15 gene under the control of CaMV 35S promoter and NOS terminator in the pCAM1300 vector into the pre-soaked seeds in N6D media for 24 hours. After 7 days of culture at $25^{\circ}C$, calli were formed on seeds cultured on the co-cultivation medium containing an antioxidant compound (1 mM dithiothreitol) and of Agrobacterium growth-inhibiting agent (3 mg/L silver nitrate). We obtained 35 and 22 transgenic plants in rice cultivars, Gopumbyeo and Ilpumbyeo, with increase of transformation efficiency by 30.4% and 22.6%, respectively compared to the general transformation method. The new method in this study would lead to reduction of substantial labor and time to generate transgenic plants.

Exposure and Risk Assessment of Melamine in Representative Korean Foods for Infants and Children (WHO 내용일일섭취량을 고려한 우리나라 영유아 어린이의 식품을 통한 멜라민 노출 및 위해 평가)

  • Oh, Chang-Hwan
    • Journal of Dairy Science and Biotechnology
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    • v.27 no.1
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    • pp.1-12
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    • 2009
  • In 2008, baby formula containing melamine was found to be responsible for a large outbreak of renal failure in infants in China. A total of 294,000 infants were hospitalized, and at least 6 babies died due to ingestion of the tainted formula. Melamine contains high levels of nitrogen (>60%), which is used as an indicator of protein content. Therefore, high levels of melamine in infant formula were thought to be the result of deliberate contamination m an attempt to increase its apparent protein content. Following inspections by China's national inspection agency, assorted products from at least 22 dairy manufacturers across China were found to have varied levels of melamine (range: 0.096196.61 mg/kg). Melamine co-exposure with cyanuric acid can induce acute melamine-cyanurate crystal nephropathy, which can lead to renal failure at much lower doses than if either compound were ingested alone. However, currently, there are very few data on melamine analogues other than cyanuric acid. At an expert meeting of the WHO and FAO held to review toxicological aspects of melamine and cyanuric acid on December 14, 2008, a new tolerable daily intake (TDI) of melamine was established that could be applied to the entire population, including infants. Therefore, a risk assessment of the various theoretical melamine contamination levels in infant formula and selected representative foods (other than infant formula and sole-source nutrition products) is urgently needed for Korean babies and children up to 7 years of age. Although the undetectable level regulation for infant formula may be low enough to guarantee the safety of babies under the age of 1 year (including premature babies), the melamine standard of 2.5 ppm for foods other than baby formula could be insufficient to protect the 95th percentile population aged 1~2 years because of this demographic's high consumption of milk, yogurt, and soy milk (hazard index = 1.79). Because TDIs are chronic values intended to protect an individual over his/her lifetime, occasional modest ingestion in excess of the TDI is not likely to be a health concern. However, children aged 1~2 years may have renal systems that are comparatively more sensitive to the crystallization of melamine and its analogues. Therefore, governmental jurisdictions may need to practice more prudent management of food items that could raise the melamine exposure for this population.

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Production of Mozzarella Cheese Analogue by Ultrafiltration (한외여과를 이용한 Mozzarella Cheese Analogue 제조에 관한 연구)

  • Lee, Sung-Hui;Song, Kwang-Young;Seo, Kun-Ho;Yoon, Yoh-Chang
    • Journal of Dairy Science and Biotechnology
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    • v.31 no.1
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    • pp.21-33
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    • 2013
  • The purpose of this study was to improve the production of Mozzarella cheese analogues manufactured using mixtures of soy milk and concentrated raw milk by performing ultrafiltration (UF) and to assess the quality of these cheeses during a 30-day storage period at $4^{\circ}C$, relative to that of Mozzarella cheese manufactured with the traditional method. The solid consistency of Mozzarella cheese analogue prepared from milk mixtures was lower than that of cheese manufactured from raw milk or soy milk and increased during storage, which is considered to be the result of decreasing water levels, as well as with increasing soy milk concentrations. In the Mozzarella cheese analogue generated using the milk mixtures, the fat content decreased with increase in the soy milk concentration, while it decreased during the storage period. Lactose levels were lowest in cheese composed of soy milk or raw milk and processed by UF, and decreased during storage in cheese produced using milk mixtures. In milk mixtures containing soy milk, the protein concentration increased with increasing amounts of raw milk and did not change during the storage period. The water-soluble nitrogen compound level was similar between cheeses and increased only slightly during storage. The amount of non-protein nitrogen compounds was higher in the cheese analogue than in the control cheese and tended to increase during storage. Analysis of the physicochemical traits of the Mozzarella cheese analogue yielded the following results: During storage, titratable acidity levels increased while pH tended to decrease. After analysis using electropherograms, it was classified as ${\alpha}$-, ${\beta}$-, or ${\kappa}$-casein. The results of rheometry tests showed that in the Mozzarella cheese analogue prepared from milk mixtures, with raw milk concentrated by UF, increases in concentration rate lead to lowered hardness, elasticity, cohesiveness, and brittleness. When cheese was produced from milk mixtures and concentrated by UF, meltability increased as the concentration rate increased, although to an extent that was less than that observed for the control cheese, and tended to increase during storage. Sensory evaluation showed that the analogue cheese was much better than the control cheese in terms of formation, appearance, and flavor.

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A Study on the Application of PbI2 Dosimetry for QA in the Electron Beam Therapy (전자선 치료의 선량 측정 QA를 위한 PbI2 선량계 적용 연구)

  • Yang, Seungwoo;Han, Moojae;Jung, Jaehoon;Choi, Yunseon;Cho, Heunglae;Park, Sungkwang
    • Journal of the Korean Society of Radiology
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    • v.14 no.5
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    • pp.517-522
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    • 2020
  • Electron beam have many factors that affect dose distribution, so even if identical settings are used, they should be identified and used for radiation treatment, and the effects on the structures in the body are sensitive, making it difficult to investigate uniform dose distribution on tumors. In this study, a dosimeter was produced using PbI2 which is a photoelectric material, and electrical characteristics were analyzed for 6, 9, and 12 MeV electronics in linear accelerators. The reproducibility test results showed that RSD were 1.1215%, 1.0160%, and 0.05137% respectively at 6, 9, and 12 MeV energies, indicating that the output signals were stable. The linearity evaluation results showed that the R2 values of the reliability indicator for straight line trend lines were 0.9999, 0.9999, and 0.9994, respectively, at 6, 9, and 12 MeV, to confirm that the output signal was proportional to PbI2 as dose increased. The PbI2 dosimeter in this study is judged to be highly applicable to electromagnet measurement and is thought to be able to be used as a basic study of electron detector through photoelectric material.