• Title/Summary/Keyword: VP16

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Modification of Animal Genotypes for the Regulation of Transgene Expression (이식유전자 발현조절을 위한 동물유전자의 조작)

  • 진동일
    • Korean Journal of Animal Reproduction
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    • v.19 no.4
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    • pp.283-291
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    • 1996
  • Transgenic animal을 응용할 수 있는 분야에서는 이식유전자의 기능을 정확하게 규명하고 이를 바탕으로 실질적인 유전적인 개량을 이루기 위해서 이식유전자의 발현을 조절할 수 있는 정교한 system이 필요하다. 유전자의 미세주입법에 의해 transgenic animal을 생산할 수 있는데 이용되고 있는 tissue-specific promoter에 의한 이식유전자의 발현조절은 필요로 하는 시기나 양 등을 인위적으로 조절하고자 하는데 한계점을 갖고 있다. 이러한 이식유전자 발현의 문제점을 극복하기 위해 효모의 recombinase나 미생물의 repressor 단백질과 이들의 binding site인 operator sequence를 이용하여 인위적으로 이식유전자의 발현을 조절할 수 있는 system이 개발되고 있다. Cre/loxP system은 site-specific recombination에 의해 DNA sequence를 제거함으로서 이식유전자의 발현을 조절할 수 있다. 이식유전자 발현의 장소와 양을 조절하기 위해서는 미생물이 이용하고 있는 repressor와 이들의 operator sequence를 적용하여 ligand binary system이 개발되었다. Lac repressor system에서는 isopropyl-$\beta$-D-thiogalactoside (IPTG)가 이식유전자 발현을 조절할 수 있는 positive regulator로서 작용하고, tetracycline-VP16 system에서는 tetracycline이나 유사물질들이 negative regulator로서 이용할 수 있다. 이러한 binary system은 transgenic animal에서 이식유전자 발현의 장소와 시기 또한 양을 효과적으로 조절하는데 적용할 수 있는 것으로 나타났다. 따라서 기존의 binary system과 함께 새로운 regulatory system의 장점을 이용하여 보다 완벽한 이식유전자의 인위적인 조절 system을 이룩함으로서 transgenic animal technology의 실용화를 앞당길 것으로 기대된다.

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항암화학요법에 의하여 골수억제가 수반된 진행암 환자에서 Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor(rhGM-CSF)의 용량과 효과에 관한 비교 연구

  • 노재경;라선영;이경희;이혜란;정현철;김주항;김병수
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.306-306
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    • 1994
  • 항암화학요법후 가장 심각한 부작용의 하나는 중성구 감소에 의한 감염이다. 본원에서는 rhGM-CSF을 이용한 제 I상 임상연구에서 150-500$\mu$g/M$^2$/day가 biologically active dose임을 보고한 바 있다. 연자들은 연세암센터에 내원하여 진행성 악성종양으로 병리조직학적 진단을 받고 항암화학요법시행후 골수억제가 예상되는 환자를 대상으로 GM-CSF 용량에 따른 안전성 및 독성을 검토하고 백혈구 감소증 및 감염의 예방, 치료효과를 분석하여 임상사용권장량을 결정하기위한 2상 연구를 대상환자의 동의를 얻은후 시행하였다. 대상환자는 37명 (여 26, 남 11)이었고, 항암제는 Adriamycin, Cisplatin, VP-16이 주로 사용되었다. 최적임상사용권장량을 결정하기 위하여 1500$\mu\textrm{g}$/M$^2$/day을 12명, 250$\mu\textrm{g}$/M$^2$/day을 12명, 350$\mu\textrm{g}$/M$^2$/day을 13명의 환자에게 투여하였다. 첫번째 항암 요법에는 rhGM-CSF을 투여하지않고 (비투여기) 두 번째 항암요법에서는 항암요법후 익일부터 10일간 연속, 매일 1회 피하주사하여 (투여기), rhGM-CSF 투여기와 비투여기의 백혈구 감소증 정도의 차이를 비교하였다.

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Papaya Ringspot Virus Coat Protein Gene for Antigen Presentation in Escherichia coli

  • Chatchen, Supawat;Juricek, Mila;Rueda, Paloma;Kertbundit, Sunee
    • BMB Reports
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    • v.39 no.1
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    • pp.16-21
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    • 2006
  • The coat protein (CP) of Papaya ringspot virus (PRSV) was analyzed for presentation of the antigenic peptide of animal virus, Canine parvovirus (CPV), in Escherichia coli (E. coli). The 45 nucleotides fragment coding for the 15-aa peptide epitope of the CPV-VP2 protein was either inserted into the PRSV-cp gene at the 5', 3' ends, both 5' and 3' ends or substituted into the 3' end of the PRSV cp gene. Each of the chimeric PRSV cp genes was cloned into the pRSET B vector under the control of the T7 promoter and transformed into E. coli. The recombinant coat proteins expressed from different chimeric PRSV-cp genes were purified and intraperitoneally injected into mice. All of the recombinant coat proteins showed strong immunogenicity and stimulate mice immune response. The recombinant coat proteins containing the CPV epitope insertion at the C terminus and at both N and C termini elicited ten times higher specific antisera in immunized mice compared with the other two recombinant coat proteins which contain the CPV epitope insertion at the N terminus and substitution at the C terminus.

Kaempferol Inhibits Enterovirus Proliferation through MAPK Signal Regulation (Kaempferol의 MAPK 신호 조절을 통한 심근염 유발 엔테로바이러스 증식 억제)

  • Jang, Jin-Hwa;Jeong, Hae-In;Lim, Byung-Kwan;Nam, Sang-Jip
    • Korean Journal of Pharmacognosy
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    • v.48 no.3
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    • pp.173-178
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    • 2017
  • We investigated the efficacy of single compound of plant extract in coxsackievirus B3 (CVB3) infection. CVB3 is a main cause of Hand-foot-mouth diseases (HFMD) and viral myocarditis in children and adult. Several single compounds of plant extract were purified by HPLC and tested as antiviral drug candidate. Among them, kaempferol was selected to effective anti-enterovirus compound by HeLa cells survival assay. CVB3 infected HeLa cells were treated with kaempferol ($100{\mu}g/ml-100ng/ml$) and their antiviral effect was confirmed. After 16 hours of treatment, HeLa cells were lysed and proteins were extracted for western blot analysis. CVB3 viral capsid protein VP1 production and transcription factor eIF4G-1 cleavage was significantly decreased in $100{\mu}g/ml$ kaempferol treatment. Virus replication was observed by virus RNA amplification. Kaempferol strongly reduced virus positive and negative strand RNA amplification. Moreover, MAPK signal induced by CVB3 infection, pERK and pmTOR, kaempferol treatment significantly inhibited the activity. Plant extract single compound, kaempferol, is a strong candidate to be developed non-toxic anti-enterovirus treatment agent.

Loss of estrogen responsiveness under hypoxia occurs through hypoxia inducible factor-l induced proteasome-dependent down regulation of estrogen receptor

  • Cho, Jung-Yoon;Kim, Duk-Kyung;Lee, Young-Joo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.70-70
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    • 2003
  • Estrogen receptor is a ligand-activated transcription factor. Its action depends on the receptor, its ligand, and its coactivator proteins. As a consequence, the concentration of the receptor is a major component that governs the magnitude of the estrogen response. Despite the extensive knowledge on mechanism of estrogen receptor action, regulation of estrogen receptor itself is not very well understood. Estrogen receptor is known to be downregulated under hypoxia leading to inhibition of estrogen receptor mediated transcription activation. We have studied mechanism of loss of estrogen responsiveness under hypoxia. We found that Hif-l${\alpha}$, a major transcription factor regulating hypoxic response, inhibited transcription of estrogen response element driven luciferase gene by expression of HIF-l${\alpha}$/vp16 construct designed to contain transcription activity under normoxia. This loss of estrogen responsiveness appears to be the result of ER${\alpha}$ downregulation. ER${\alpha}$was downregulated at the levels of ligand-biding and protein within l2-24h, and the response was blocked by the proteasome inhibitor MG132, protein synthesis inhibitor cyclohexamide, and tyrosine kinase inhibitor Genistein. These results demonstrate that Hif-l${\alpha}$ downregulates ER${\alpha}$ by proteasome dependent pathway.

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Hunt-Hess and Fisher Grades as Predicting Factors for Chronic Hydrocephalus in Surgically Treated Ruptured Aneurysm (수술적 치료를 받은 파열성 뇌동맥류환자에서의 예후와 뇌실-복강 단락술의 예측인자로써의 Hunt-Hess Grade와 Fisher Grade)

  • Hong, Chang Ki;Park, Chong Oon;Hyun, Dong Keun;Ha, Young Soo
    • Journal of Korean Neurosurgical Society
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    • v.30 no.1
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    • pp.60-65
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    • 2001
  • Objective : The popular grading systems in use, such as Hunt-Hess grade and Fisher scale score, are based primarily on the patient's clinical conditions or computerized tomography score after aneurysmal subarachnoid hemorrhage(SAH). The author investigated whether the need for ventriculoperitoneal(VP) shunt for chronic hydrocephalus and outcome can be predicted by Hunt-Hess grade and Fisher scale. Methods : A series of 146 patients admitted to our hospital from August 1991 to July 1999, who presented with SAH and underwent craniotomy for aneurysm clipping were studied retrospectively. Chronic hydrocephalus was defined as clinically and radiographically demonstrated hydrocephalus that lasted 2 weeks or longer after initial hemorrhage which required shunting. Patients were evaluated based on following factors : Hunt-Hess grade, Fisher scale, age, sex, hypertension, aneurysm location, and intervals from aneurysm rupture to operation. Results : The overall mortality rate of the study group was 8.2%. Hunt-Hess grade(p=0.001) or Fisher scale (p=0.001) at all pretreatment times was significantly correlated with outcome. In addition, there was an increased risk of poor outcome in older age(65<). However, there were statistically no significant relationship between outcome and sex, location of aneurysm, hypertension, and interval from aneurysmal rupture to operation(p>0.05). Of 134 surviving patients, 16 patients(12%) underwent VP shunt placement secondary to chronic hydrocephalus. Hunt-Hess grade(p=0.001) is more predictive of chronic hydrocephalus than Fisher scale(p=0.146). Aneurysm location was significantly correlated with development of chronic hydrocephalus (p<0.05), without significant correlations in sex, age, hypertension. IVH, and ICH. Conclusion : This study suggests that there is a high clinical correlation between outcome and Hunt-Hess grades and Fisher scales on admission, but Hunt-Hess grade is more predictive for chronic hydrocephalus than Fisher scale. In addition, age(<65 yrs) is the significant factor for prediction of outcome. There was a trend of increasing risk for chronic hydrocephalus according to aneurymal location.

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Evaluation of the Radiopacity of Contemporary Luting Cements by Digital Radiography (디지털방사선촬영술을 이용한 합착용 시멘트의 방사선불투과성 평가)

  • An, Seo-Young;Lee, Du-Hyeong;Lee, Kyu-Bok
    • Journal of Dental Rehabilitation and Applied Science
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    • v.29 no.4
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    • pp.377-383
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    • 2013
  • This study examined the radiopacity of eight contemporary luting cements by direct digital radiography. Five disc-shaped specimens ($5mm{\times}1mm$) were prepared for each material tested (BisCem, Clearfil SA Luting, Duolink, Maxcem Elite, Multilink Speed, Panavia F 2.0, RelyX Unicem Clicker, V-link). The specimens were radiographed using a Kodak CS 7600 image plate (Carestream Health, Inc., Rochester, NY, USA) and an aluminum step wedge with a range of thicknesses (1.5 to 16.5 mm in 1.5 mm increments) and a 1 mm tooth used as a reference. A dental X-ray machine Kodak 2200 Intraoral X-ray System (Carestream Health, Inc., Rochester, NY, USA), operating at 70 kVp, 4 mA, 0.156 s and a source-to-sample distance of 30 cm, was used. According to international standards, the radiopacity of the specimens was compared with that of an aluminum step wedge using NIH ImageJ software (available at http://rsb.info.nih.gov/ij/).The data was analyzed by ANOVA and a Tukey's post hoc test. Maxcem Elite (5.66) showed the highest radiopacity of all materials, followed in order by Multilink Speed (3.87) and V-link (2.83). The radiopacity of Clearfil SA Luting (1.35), BisCem (1.33), Panavia F 2.0 (1.29) and Duolink (1.10) were between enamel (1.79) and dentin (0.19). RelyX Unicem Clicker (0.71) showed the lowest radiopacity, which was higher than that of dentin. All materials showed a radiopacity above the minimum recommended by the International Organization for Standardization and the American National Standards/American Dental Association with the exception of RelyX Unicem Clicker.

A Study on Radiographical Conditions and Exposure Doses During Chest Radiography at Medical Facilities in Pusan (부산지역 의료기관의 흉부촬영 조건과 피폭선량에 관한 조사연구)

  • Jeon, Sung-Oh;Cho, Young-Ha
    • Journal of radiological science and technology
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    • v.20 no.2
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    • pp.49-55
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    • 1997
  • This study was carried out to investigate radiographical and operating conditions of X-ray units and exposure doses to patients during chest radiography, so that the results could provide basic data used for reducing the exposure dose and for providing the diagnostic information with better quality. The conditions and exposure doses of 100 X-ray units mainly used for chest radiography were examined and also 100 radiological technologists mainly handling those apparatus at 76 medical facilities in Pusan were surveyed using a questionnaire from October 1 to December 31 in 1995. The following results were obtained from the study : 1. It was found that most units were capable of taking a high tube voltage radiography by showing 67% of the units equipped with the maximum tube voltage of 150 kV, 94% with more than 500 mA for the rating capacity and 85% with the full wave type of a signal phase. 2. For actual chest radiographical conditions, however, 80% of the units were operated at $60{\sim}100\;kVp$ and only 14% at 100 kVp and over for the high tube voltage. 3. The average exposure time was less than 0.1 second, and eighty four percent of the units adapted the X-ray tube currents ranging from 200 to 300 mA, 80% the focus-film distances between 180 and 210 cm, and 63% the focus sizes of more than 2.0 mm. 4. Most units(98%) employed additional filters made of aluminum, 75% the thickness of filters less than 2.0 mm, and only 2 units the compound filters. 5. Ortho chromatic system was only adopted in 13% of screen film system for the units, and 73% used the grid ratio at 8 : 1 for the low tube voltage during chest radiography. 6. The average exposure dose of all X-ray units during chest radiography was $371\;{\mu}Sv$ with a difference of about 16 times between the minimum to the maximum, and $386\;{\mu}Sv$ both at hospitals and at health centers, followed by $380\;{\mu}Sv$ at general hospitals and $263\;{\mu}Sv$ at university hospitals without showing any statistically significant differences. In conclusion, since patients during chest radiography at medical facilities in Pusan exposed to high levels of radiation, it is recommended that appropriate added filters and grids necessary for the high tube voltage radiography and high-speed screen systems should be adopted and used as soon as possible in order to reduce exposure dose to the patients.

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Low-Tube-Voltage CT Urography Using Low-Concentration-Iodine Contrast Media and Iterative Reconstruction: A Multi-Institutional Randomized Controlled Trial for Comparison with Conventional CT Urography

  • Kim, Sang Youn;Cho, Jeong Yeon;Lee, Joongyub;Hwang, Sung Il;Moon, Min Hoan;Lee, Eun Ju;Hong, Seong Sook;Kim, Chan Kyo;Kim, Kyeong Ah;Park, Sung Bin;Sung, Deuk Jae;Kim, Yongsoo;Kim, You Me;Jung, Sung Il;Rha, Sung Eun;Kim, Dong Won;Lee, Hyun;Shim, Youngsup;Hwang, Inpyeong;Woo, Sungmin;Choi, Hyuck Jae
    • Korean Journal of Radiology
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    • v.19 no.6
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    • pp.1119-1129
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    • 2018
  • Objective: To compare the image quality of low-tube-voltage and low-iodine-concentration-contrast-medium (LVLC) computed tomography urography (CTU) with iterative reconstruction (IR) with that of conventional CTU. Materials and Methods: This prospective, multi-institutional, randomized controlled trial was performed at 16 hospitals using CT scanners from various vendors. Patients were randomly assigned to the following groups: 1) the LVLC-CTU (80 kVp and 240 mgI/mL) with IR group and 2) the conventional CTU (120 kVp and 350 mgI/mL) with filtered-back projection group. The overall diagnostic acceptability, sharpness, and noise were assessed. Additionally, the mean attenuation, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and figure of merit (FOM) in the urinary tract were evaluated. Results: The study included 299 patients (LVLC-CTU group: 150 patients; conventional CTU group: 149 patients). The LVLC-CTU group had a significantly lower effective radiation dose ($5.73{\pm}4.04$ vs. $8.43{\pm}4.38mSv$) compared to the conventional CTU group. LVLC-CTU showed at least standard diagnostic acceptability (score ${\geq}3$), but it was non-inferior when compared to conventional CTU. The mean attenuation value, mean SNR, CNR, and FOM in all pre-defined segments of the urinary tract were significantly higher in the LVLC-CTU group than in the conventional CTU group. Conclusion: The diagnostic acceptability and quantitative image quality of LVLC-CTU with IR are not inferior to those of conventional CTU. Additionally, LVLC-CTU with IR is beneficial because both radiation exposure and total iodine load are reduced.

Embedded System Integrated Prototyping Mechanism Based on Reusable Component (재사용 가능한 컴포넌트 기반의 임베디드 시스템 통합 프로토타이핑 기법)

  • Sukmana, Husni Teja;Lee, Jeong-Bae;Rim, Kee-Wook;Hwang, Young-Sup;Kim, Young-Jin;Ahn, Sung-Soon
    • The KIPS Transactions:PartA
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    • v.16A no.3
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    • pp.199-208
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    • 2009
  • Recently, there are many embedded system prototyping tools for helping embedded system designers to trial their product before it releases to the market. A prototype is very important for early embedded system design to grasp the desire functions, to get a good performance, to create delightful user interface, and to increase the valuable of the product. Prototyping tools can be classified by three categories: Physical, Virtual and Modeling prototyping. The integration of these prototyping tools becomes valuable for speed up time-to-market and for decrease design cost when design embedded system. The problem comes up because these tools sometime do not provide an instrument for communicating each other. In this paper, we propose a flexible and reusable mechanism for integrate these tools base on JavaBeans and ActiveX technology. We show how this mechanism can be employed in various prototyping tools.