• Title/Summary/Keyword: Apc

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CHEMOPREVENTION OF COLON CANCER BY THE KOREAN FOOD STUFFS COMPONENTS

  • Kim, Dae-Joong;Shin, Dong-Hwan;Ahn, Byeong-Woo;Jang, Dong-Deuk;Hiroyuki Tsuda;Shoji Fukushima
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05b
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    • pp.106.2-132
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    • 2002
  • 형질전환 (유전자 결핍; Knockout) Min 마우스를 이용하여 대장암 발생에서 배추, 양배추 주성분인 indole-3-carbinol (I3C)의 대장암 예방효과를 규명하고자 하였다. 실험동물로는 C57BL/6J-Apc$^{min/+}$(Min 마우스)계의 5내지 6주령의 수컷 이형접합체 형질전환 마우스 70마리와 C57BL/6J계의 동일 산자, 동일 주령의 수컷 wildtype 비형질전환 마우스 10kfl를 The Jackson Laboratory 사 (Bar harber, ME, USA)로부터 직접 구입하였다. C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 (Min)마우스 70마리를 각 군 20내지 25마리씩 세군으로 나누었다. Group 1에는 20마리, Group 2에는 25마리, Group 3에는 25마리를 배치하고, I3C 투여 실험군 (Group 1과 2)에는 실험시작시에 AIN-76A 분말사료에 I3C가 각각 100 및 300ppm이 함유되도록 조제하여 공급하였다. 그리고 실험군(Group 3)에는 실험시작부터 종료시까지 AIN-76A 정제고형사료(Teklad사, WI, USA)를 자유로이 급이하였다. 각군간의 체중, 사료 및 음수소비량을 매 2주마다 측정하였고, 10주간 (16주령)의 실험종료시에는 최종체중과 간장, 신장, 비장 등의 장기무게를 측정하여 상대장기 무게비를 산출하였다. 대조군으로서 C57BL/6J계의 동일 산자, 동일 주령의 수컷 wildtype 비형질전환 마우스 10마리는 같은 조건의 사육실에서 AIN-76A 정제고형사료를 33주간 자유로이 급이하였다. 실험동물은 부검전에 하룻밤 동안 절식하고 이산화탄소 흡입 마취하에서 흉대동맥을 절단하여 방혈하고 각 장기(심장, 폐, 위)를 적출하여 생리심염수에 넣어 장기무게를 측정하고 포르말린에 고정하였다. 소장과 대장의 검사를 위하여 위의 식도부위와 직장을 실로 결찰하여 적출하고 생리심염수를 주입하여 팽창시켜, 십이지장, 공장, 및 회장, 그리고 대장으로 나누어 여과지에 펼친 후 포르말린에 고정하였다. 소장과 대장은 육안 및 자동 영상분석길ㄹ 이용한 분석이 끝난 후에 각 부위별로 4-6개의 절편을 작제하여 포르말린에 재고정하고, 통상적인 조직처리과정, 파리핀 포매 및 3-4$\mu$m 두께의 조직절편을 제작하여 H&E 염색을 실시하여 현미경으로 검경하였다. 약 1주일간의 포르말린 고정이 끝난 소장 및 대장을 부위별, 별 종양개수 및 분포를 자동영상분석기(Kontron Co. Ltd., Germany)로 분석하였다. 체의 변화, 장기무게, 사료소비량 및 마리당 종양의 개수에 대한 통계학적 유의성 검증을 위하여 Duncan's t-test로 통계처리 하였고, 종양 발생빈도에 대하여는 Likelihood ration Chi-square test로 유의성을 검증하였다. C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스에 AIN-76A 정제사료만을 투여한 대조군의 대장선종의 발생률은 84%(Group 3; 21/25례)로써 I3C 100ppm 및 300ppm을 투여한 경우에 있어서는 각군 모두 60%(Group 1; 12/20 례, Group 2; 15/25 례)로 감소하는 경향을 나타내었다. 대장선종의 마리당 발생개수에 있어서는 C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스에 AIN-76A 정제사료만을 투여한 대조군은 1.40$\pm$0.24(100%)에 비하여 I3C 저농도 투여 실험군(Group 1; 0.85$\pm$0.23; 61%, P<0.01), 그리고 I3C 고농도 투여 실험군(Group 2 ; 1.32$\pm$0.29 ; 94%)의 순으로 감소하였다. 선종의 크기별 종양의 발생개수의 분포에 있어서 I3C 저농도 투여 실험군에 있어서는 선종의 크기가 3mm이하의 수가 현저하게 감소하였다. C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스에 AIN-76A 정제사료만을 투여한 대조군의 부위별 소장선종의 발생수는 십이지장부위를 제외하고 각 군에서 유의한 변화는 관찰되지 않았다. 십이지장 종양의 발생개수에서만 I3C 저농도 투여 실험군(Group 1 ; 3.11$\pm$0.85)이 대조군 (Group 3: 1.48$\pm$0.35) 및 I3C 고농도 투여 실험군(Group 2: 1.56$\pm$0.47)에 비하여 유의성 있게 증가하였다. (P<0.05). 따라서 I3C은 소장에서는 암예방 효과가 뚜렷하지 않으나, 대장에 대한 암에방 효과가 있을 것으로 생각된다. 소장 및 대장을 제외한 간장, 신장, 비장, 심장, 폐 그리고 위 등의 기타 장기에서의 조직병리학적 변화는 관찰되지 않았다. 소장 및 대장의 종양은 선종(polyps)으로 관찰되었다. 지난 10여년간 형질전환 및 유전자 결핍 실험동물의 종류가 기하 급수적으로 증가하여 이용되고 있다. 가족성 대장 선종성 용종증(FAP)의 대표적인 모델로 이용되고 있는 C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스를 사용하여 배추나 양배추의 주요성분인 Indole-3-carbinol(I3C)의 대장암 예방효과가 있는지를 검색하여 본 결과 AIN-76A정제사료만을 투여한 대조군의 대장선종의 발생률 84%에 비하여 I3C 100 및 300ppm을 투여한 실험군에 있어서 각군 모두 60%로서 감소하는 경향을 나타내었으며, 대장선종의 마리당 발생개수에 있어서는 대조군의 1.40$\pm$1.041를 100%로 환산하였을 경우 I3C 저농도 및 고농도 투여 실험군에서는 각각 약 61%와 94%를 나타내여 감소하였다. 특히 대장선종의 크기별 분포에 있어서 선종의 크기가 3mm이하의 수가 현저하게 감소하였다. 따라서 저농도 I3C의 투여는 실험적 유전성 가족성 대장 선종성 용종증 모델에 있어서 어느정도 암 예방효과가 있는 것으로 생각된다. 그러나 소장 선종의 발생에는 별 영향이 없는 것으로 생각된다. 그러나 본 실험에 사용된 C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스는 실험개시 시점이 7내지 8주령이 경과하여 이미 태생기부터 소장 및 대장의 선종 발생이 진행되어 온 것을 감안하고 특히 비스테로이드계 항염증 소염제(NSAIDS)와 같은 강력한 COX-2억제제가 아님을 고려하면, 상당한 선종의 발생을 억제할 수 있는 가능성이 매우 높다고 생각한다. 또한 이제까지 배추나 양배추 성분의 복합성분들에 대한 실험적 대장암 모델에서의 촉진효과 등에 대한 보고들이 있어 온 점을 고려할 때 위암(Kim 등, 1994) 간암(Kim 등, 1994), 유방암(Grubbs, 등, 1995; Bradlow 등, 1995)에 대한 예방효과가 있을 것으로 생각된다. 앞으로 이러한 종양조직내에서의 COX-2 및 iNOS mRNA와 단백질의 발현정도를 분자병리학적으로 연구중에 있으며, 향후 십자화과식물 성분인 indole-3-carbinol이 마우스뿐 만 아니라 랫드의 화학발암물질에 의한 대장종양에 대한 억제효과 있는지 연구 필요가 있다. Min 마우스와 같은 형질 전환(유전자결핍;knockout) 실험동물을 이용한 새로운 중기 발암성 시험범의 확립을 통한 각종 환경 유해물질의 발암성 유무 및 COX-2 억제작용이 있는 식품인자의 암예방 후보물질을 체계적으로 검색하는데 유용하게 활용될 수 있을 것으로 생각한다.

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Age-period-cohort Analysis of Healthy Lifestyle Behaviors Using the National Health and Nutrition Survey in Japan

  • Okui, Tasuku
    • Journal of Preventive Medicine and Public Health
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    • v.53 no.6
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    • pp.409-418
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    • 2020
  • Objectives: This study conducted an age-period-cohort (APC) analysis of trends in healthy lifestyle behaviors in Japan. Methods: We used National Health and Nutrition Survey data on salt intake and prevalence of smoking, drinking, and physical activity between 1995 and 2018 in Japan. Age groups were defined from 20 years to 69 years old in 10-year increments. Cohorts were defined for each age group of each year with a 1-year shift, and cohorts born in 1926-1935 (first cohort) until 1989-1998 (last cohort) were examined. We conducted a Bayesian APC analysis, calculating estimated values for each behavior by age group, period, and cohort. Results: Estimated salt intake decreased from cohorts born in the 1930s to the 1960s, but increased thereafter in both genders, and the magnitude of increase was larger for men. Estimated smoking prevalence increased in the cohorts starting from the 1930s for men and the 1940s for women, and then decreased starting in the cohorts born in the 1970s for both genders. Although estimated drinking prevalence decreased starting in the cohorts born in approximately 1960 for men, for women it increased until the cohorts born in approximately 1970. Estimated physical activity prevalence decreased starting in the cohorts born in the 1940s in both genders, but the magnitude of decrease was larger for women. Conclusions: Trends in cohort effects differed by gender, which might be related to changes in the social environment for women. Improvements in dietary and exercise habits are required in more recently born cohorts of both genders.

A Study on the Sharing of Research Data in Library and Information Science Field (문헌정보학 분야 연구데이터 공유에 관한 연구)

  • Cho, Jane
    • Journal of the Korean Society for information Management
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    • v.34 no.4
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    • pp.59-79
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    • 2017
  • This study analyzed the type, subject and open level of research data in the field of library and information science field shared by Figshare, and statistically analyzed the characteristics of data with relatively high recyclability. The results of the analysis showed that datasets and papers were most common data types, and open access and research data were the most common keywords of data, and that 70% of the data were published in a form that can not be processed mechanically such as pdf. As a result of analysis of the relationship between characteristics of research data and degree of sharing, open access areas such as APC (Article Processing Charge) were found to be most common in the subject. However in data type, gray literature such as paper found to be highly utilized rather than dataset.

A New Artificial Immune System Based on the Principle of Antibody Diversity And Antigen Presenting Cell (Antibody Diversity 원리와 Antigen Presenting Cell을 구현한 새로운 인공 면역 시스템)

  • 이상형;김은태;박민용
    • Journal of the Institute of Electronics Engineers of Korea CI
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    • v.41 no.4
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    • pp.51-58
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    • 2004
  • This paper proposes a new artificial immune approach to on-line hardware test which is the most indispensable technique for fault tolerant hardware. A novel algorithm of generating tolerance conditions is suggested based on the principle of the antibody diversity. Tolerance conditions in artificial immune system correspond to the antibody in biological immune system. In addition, antigen presenting cell (APC) is realized by Quine-McCluskey method in this algorithm and tolerance conditions are generated through GA (Genetic Algorithm). The suggested method is applied to the on-line monitoring of a typical FSM (a decade counter) and its effectiveness is demonstrated by the computer simulation.

A Study on the Drinking Water Quality for Primary Lunch School in Seoul (서울지역 급식 국민학교의 음용수 수질에 관한 연구)

  • 이원묘;이용옥;방형애
    • Journal of Environmental Health Sciences
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    • v.21 no.1
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    • pp.7-20
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    • 1995
  • The aims of this study are to enhance the students' knowledge of the drinking water and its reliability by investigating drinking water situation on the drinking water. The results are as following 1. Status and drinking behavior about school drinking water (1) 97.82% of the schools are using the tap water as the resource of drinking water. (2) 46 schools are in possession of water tank and 18 schools of them are using the water tank as the resource of drinking water. The clearing and sanitization of the tank are carried out once in a year with hypochloronatrium by the low-level officials. (3) 51.28% of the schools are providing the students with drinking water and 75% of them with boiled water. The drinking water supply managers are low-level officials, nurse teachers, and dietitian. 2. Analysis of the drinking water quality (1) Most of the drinking water provided by the school are tap water 35.8%, barely tea 5.85%, filtered water 6.3%, ground water 1.1% and all turned out to be suitable for drinking. (2) The drinking water carried from home turned out to be unsuitable for drinking except pH criterion, especially the test of APC(Aerobic Plate Count) and Coliform group showed worse degree. These results were caused by the hygiene problem and maltreatment in water container.

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Environmental Toxic Agents on Genetic Material and Cellular Ativity V. The Roles of DNA Polymerases on Mutagen-Induced DNA Repair Synthesis in Relation to Cell Cycle in Chinese Hamster Ovary Cells (환경성 유해요인이 유전물질과 세포활성에 미치는 영향 V. CHO세포에서 세포주기에 따라 돌연변이원에 의해 유발된 DNA회복합성에 미치는 DNA중합효소의 역할)

  • 엄경일;김춘광;신은주;문용석;이천복
    • Environmental Mutagens and Carcinogens
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    • v.9 no.1
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    • pp.23-32
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    • 1989
  • Chinese hamster ovary (CHO)-K1 cells echibited a differential sensitivity in the process of DNA repair synthesis induced by ethyl methanesulfonate (EMS) or bleomycin (BLM) in relation to cell cycle. Two assays were employed in this study: alkaline elution and unscheduled DNA synthesis. The post-treat-ment with aphidicolin (APC), an inhibitor of DNA polymerase alpha, inhibited DNA repair synthesis induced by EMS in G2 phase, while APC did not show any effect on BLM-induced DNA repair synthesis in all phases. On the other hands, the 2', 3'-dideoxythymidine (ddTTP), an inhibitor of DNA polymerase beta, inhibited DNA repair synthesis induced by EMS or BLM in both of G1 and G2 phases. These results suggested that the involvement of DNA polymerase alpha and beta in DNA repair was dependent on cell stage or used chemical agent.

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Thrombin inhibits HMGB1-mediated proinflammatory signaling responses when endothelial protein C receptor is occupied by its natural ligand

  • Bae, Jong-Sup;Rezaie, Alireza R.
    • BMB Reports
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    • v.46 no.11
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    • pp.544-549
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    • 2013
  • High mobility group box 1 (HMGB1) is involved in the pathogenesis of vascular diseases. Unlike activated protein C (APC), the activation of PAR-1 by thrombin is known to elicit proinflammatory responses. To determine whether the occupancy of EPCR by the Gla-domain of APC is responsible for the PAR-1-dependent antiinflammatory activity of the protease, we pretreated HUVECs with the PC zymogen and then activated PAR-1 with thrombin. It was found that thrombin downregulates the HMGB1-mediated induction of both TNF-${\alpha}$ and IL-6 and inhibits the activation of both p38 MAPK and NF-${\kappa}B$ in HUVECs pretreated with PC. Furthermore, thrombin inhibited HMGB1-mediated hyperpermeability and leukocyte adhesion/migration by inhibiting the expression of cell adhesion molecules in HUVECs if EPCR was occupied. Collectively, these results suggest the concept that thrombin can initiate proinflammatory responses in vascular endothelial cells through the activation of PAR-1 may not hold true for normal vessels expressing EPCR under in vivo conditions.

Age-period-cohort Analysis of Cardiovascular Disease Mortality in Japan, 1995-2018

  • Okui, Tasuku
    • Journal of Preventive Medicine and Public Health
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    • v.53 no.3
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    • pp.198-204
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    • 2020
  • Objectives: This study aimed to analyze the mortality of heart disease (HD), ischemic heart disease (IHD), and cerebrovascular disease (CeVD) through an age-period-cohort (APC) analysis. Methods: We used data on mortality due to cardiovascular disease from 1995 to 2018 in Japan, as determined by Vital Statistics. Age groups from 0 years to 99 years were defined by 5-year increments, and cohorts were defined for each age group of each year with a 1-year shift. We used Bayesian APC analysis to decompose the changes in the diseases' mortality rates into age, period, and cohort effects. Results: The period effects for all diseases decreased during the analyzed periods for both men and women. The cohort effects for men increased substantially in cohorts born from around 1940 to the 1970s for all types of cardiovascular diseases. The cohort effects of HD decreased in the cohorts born in the 1970s or later for both men and women. Regarding IHD and CeVD, either a non-increase or decrease of cohort effects was confirmed for cohorts born in the 1970s or later for men, but the effects for women showed a continuously increasing trend in the cohorts born in the 1960s or later. Conclusions: The cohort effects for IHD and CeVD showed increasing trends in younger generations of women. This suggests that preventive approaches against cardiovascular diseases are needed, particularly for women.

A 12.5-Gb/s Optical Transmitter Using an Auto-power and -modulation Control

  • Oh, Won-Seok;Park, Kang-Yeob;Im, Young-Min;Kim, Hwe-Kyung
    • Journal of the Optical Society of Korea
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    • v.13 no.4
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    • pp.434-438
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    • 2009
  • In this paper, a 12.5-Gb/s optical transmitter is implemented using 0.13-${\mu}m$ CMOS technology. The optical transmitter that we constructed compensates temperature effects of VCSEL (Vertical cavity surface emitting laser) using auto-power control (APC) and auto-modulation control (AMC). An external monitoring photodiode (MPD) detects optical power and modulation. The proposed APC and AMC demonstrate 5$\sim$20-mA of bias-current control and 5$\sim$20-mA of modulation-current control, respectively. To enhance the bandwidth of the optical transmitter, an active feedback amplifier with negative capacitance compensation is exploited. The whole chip consumes only 140.4-mW of DC power at a single 1.8-V supply under the maximum modulation and bias currents, and occupies the area of 1280-${\mu}m$ by 330-${\mu}m$ excluding bonding pads.

Phagocytic Uptake of Surface modified PLGA Microspheres Using Dendritic Cell

  • Kim, Ji-Seon;Lee, Young-Sung;Lee, Jung-Gil;Park, Jeong-Sook;Lee, Jong-Kil;Chung, Youn-Bok;Han, Kun
    • Journal of Pharmaceutical Investigation
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    • v.41 no.3
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    • pp.185-190
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    • 2011
  • The purpose of this study was to evaluate the phagocytic uptake of surface modified PLGA microspheres containing ovalbumin (OVA) into dendritic cell. In order to find the most suitable formulation for targeted delivery to antigen presenting cells (APC), OVA was encapsulated by a double emulsion solvent evaporation method with three PLGA microspheres (PLGA 50:50, PLGA 75:25 and PLGA 85:15) and two surface modified microspheres by chitosan and sodium dodecyl sulfate (SDS). Physicochemical properties were evaluated in terms of size, zeta potential, encapsulation efficiency, different scanning calorimeter (DSC), x-ray diffraction, morphology, and OVA release test from microspheres. Phagocytic activity was estimated using dendritic cells and analyzed by fluorescence activated cell sorter (FACS). The result showed that zeta potential of PLGA particles was changed to positive by the chitosan modification. The release profile of chitosan modified PLGA microspheres exhibited sustained release after initial burst. The chitosan modified microspheres had higher phagocytic uptake than the other microspheres. Such physicochemical properties and phagocytic uptake studies lead us to conclude that chitosan modified microspheres is more suitable formulation for the targeted delivery of antigens to APC compared with the other microspheres.