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Gemcitabine-induced Cell Death in Lung Cancer Cells : the Role of p53 (폐암 세포에서 Gemcitabine에 의한 세포 사멸과 p53의 역할)

  • Kim, Doh-Hyung;Bae, Gang-U;Yong, Wha-Shim;Choi, Eun-Kyung;Kim, Youn-Seup;Park, Jae-Seuk;Jee, Young-Koo;Lee, Kye-Young
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.3
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    • pp.275-284
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    • 2002
  • Background : Gemcitabine is a new anti-cancer agent for treating non-small cell lung cancer. Functioning as an antimetabolite, it induces anti-cancer effects by suppressing DNA synthesis after being incorporated into the DNA as a cytosine arabinoside analogue. When Gemcitabine is incorporated into the DNA, the p53 gene may be activated by induction of the DNA defect. However, there are a few studies on the molecular mechanisms of Gemcitabine-induced cell death. This study examined the role of p53 in Gemcitabine-induced cell death. Methods : A549 and NCl-H358 lung cancer cells were used in this study. The cell viability test was done using a MTT assay at Gemcitabine concentrations of 10nM, 100nM, 1uM, 10uM and 100uM. A FACScan analysis with propium iodide staining was used for the cell cycle analysis. Western blot analysis was done to investigate the extent of p53 activation. For the functional knock-out of p53, stable A549-E6 cells and H358-E6 cells were transfected pLXSN-16E6SD which is over expresses the human papilloma virus E6 protein that constantly degrades p53 protein. The functional knock out of p53 was confirmed by Western blot analysis after treatment with a DNA damaging agent, doxorubicine. Results : Gemcitabine exhibited cell toxicity in dose-dependent fashion. The cell cycle analysis resulted in an S phase arrest. Western blot analysis significant p53 activation in time-dependent manner. Gemcitabine-induced cytotoxicity was reduced by 20-30% in the A549-E6 cells and the 30-40% in H358-E6 cells when compared with the A549-neo and H358-neo control cells. Conclusion : Gemcitabine induces an S phase arrest, as expected for the anti-metabolite, and activates the p53 gene, Furthermore, p53 might play an important role in Gemcitabine-induced cell death. Further investigation into the molecular mechanisms on how Gemcitabine activates the p53 gene and its signaling pathway are recommended.

Pulmonary Oxalosis Caused by Aspergillus Niger Infection (Aspergillus Niger 감염에 의한 폐옥살산염 1예)

  • Cho, Gye Jung;Ju, Jin Young;Park, Kyung Hwa;Choi, Yoo-Duk;Kim, Kyu Sik;Kim, Yu Il;Kim, Soo-Ok;Lim, Sung-Chul;Kim, Young-Chul;Park, Kyung-Ok;Nam, Jong-Hee;Yoon, Woong
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.5
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    • pp.516-521
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    • 2003
  • The Aspergillus species produces metabolic products that play a significant role in the destructive processes in the lung. We experienced a case of chronic necrotizing pulmonary aspergillosis caused by an Aspergillus niger infection, which contained numerous calcium oxalate crystals in the necrotic lung tissue. A 46-year-old man, who had a history of pulmonary tuberculosis, presented with high fever, intermittent hemoptysis and pulmonary infiltrations with a cavity indicated by the chest radiograph. Despite being treated with several antibiotics and anti-tuberculosis regimens, the high fever continued. The sputum cultures yielded A. niger repeatedly, and intravenous amphotericin B was then introduced. The pathological specimen obtained by a transbronchial lung biopsy revealed numerous calcium oxalate crystals in a background of acute inflammatory exudates with no identification of the organism. Intravenous amphotericin B was continued at a total dose of 1600 mg, and at that time he was afebrile, although the intermittent hemoptysis continued. On the $63^{rd}$ hospital day, a massive hemoptysis (about 800 mL) developed, which could not be controlled despite embolizing the left bronchial artery. He died of respiratory failure the next day. It is believed that the oxalic acid produced by A. niger was the main cause of the patient's pulmonary injury and the ensuing massive hemoptysis.

The Comparison of the Effect of Cigarette and Stop Smoking-aiding Cigarette on Release of IL-6 from Bronchial Epithelial Cell (일반담배(Cigarette)와 금연 보조 담배(금연초, 허브담배, 쑥 담배)의 기관지 상피세포에서 IL-6유리 효과비교)

  • Kim, Myoung Chan;Jung, Jeil;Jung, Jong Hoon;Kim, Hak Ryul;Yang, Sei Hoon;Jeong, Eun Taik;Kim, Hui Jung
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.5
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    • pp.530-535
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    • 2005
  • Background and Aims : Cigarette smoking induces an inflammatory response in the airways, which may play a key role in the pathogenesis of chronic obstructive pulmonary disease. Interleukin-6 (IL-6) is one of the cytokines that plays an important role in inducing bronchial inflammation. The aim of this study was to determine if the level of the pro-inflammatory cytokine, Interleukin-6, is increased when the bronchial epithelial cells are exposed to a cigarette smoke extract (CSE) and an extract from stop smoking-aiding cigarettes, and examined the safety of these commercially available stop smoking-aiding cigarettes. Method : Bronchial epithelial cells were exposed to CSE from cigarette and stop smoking-aiding cigarettes for 24 hours. ELISA was used to measure the IL-6 levels in the supernatant from each condition. The IL-6 mRNA levels were measured by Taqman Real time RT-PCR. N-acetyl-L-cysteine(NAC) was added to each condition to determine if NAC can inhibit the release of IL-6 from the bronchial epithelial cells when they are exposed to CSE from cigarette and stop smoking-aiding cigarettes. Result : When bronchial epithelial cells were exposed to a CSE from cigarettes and stop smoking-aiding cigarettes, each type of CSE stimulated IL-6 production from the bronchial epithelial cells. The IL-6 mRNA level in the Bronchial epithelial cells was also elevated and NAC was found to inhibit the release of IL-6 from bronchial epithelial cells when they were exposed to the CSE from cigarettes and stop smoking-aiding cigarettes. Conclusion : Commercially available stop smoking-aiding cigarette can induce bronchial inflammation and can be harmful to smokers. Therefore, the safety of these cigarettes for smoking cessation should be evaluated.

Quantitative Evaluation of the Accuracy of 3D Imaging with Multi-Detector Computed Tomography Using Human Skull Phantom (두개골 팬텀을 이용한 다검출기 CT 3차원 영상에서의 거리측정을 통한 정량적 영상특성 평가)

  • 김동욱;정해조;김새롬;유영일;김기덕;김희중
    • Progress in Medical Physics
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    • v.14 no.2
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    • pp.131-140
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    • 2003
  • As the importance of accuracy in measurings of 3-D anatomical structures continues to be stressed, an objective and quantitative of assessing image quality and accuracy of 3-D volume-rendered images is required. The purpose of this study was to evaluate the quantitative accuracy of 3-D rendered images obtained with MDCT, scanned at various scanning parameters (scan modes, slice thicknesses and reconstruction slice thickness). Twelve clinically significant points that play an important role for the craniofacial bone in plastic surgery and dentistry were marked on the surface of a dry human skull. The direct distances between the reference points were defined as gold standards to assess the measuring errors of 3-D images. Then, we scanned the specimen with acquisition parameters of 300 mA, In kVp, and 1.0 sec scan time in axial and helical scan modes (pitch 3:1 and 6:1) at 1,25 mm, 2.50 mm, 3.75 mm and 5.00 mm slice thicknesses. We performed 3-D visualizations and distance measurements with volumetric analysis software and statistically evaluated the quantitative accuracy of distance measurements. The accuracy of distance measurements on the 3-D images acquired with 1.25, 2.50, 3,75 and 5.00 mm slice thickness were 48%, 33%, 23%, 14%, respectively, and those of the reconstructed 1.25 mm were 53%, 41%, 43%, 36% respectively. Meanwhile, there were insignificant statistical differences (P-value<0.05) in the accuracy of the distance measurements of 3-D images reconstructed with 1.25 mm thickness. In conclusion, slice thickness, rather than scan mode, influenced the quantitative accuracy of distance measurements in 3-D rendered images with MDCT. The quantitative analysis of distance measurements may be a useful tool for evaluating the accuracy of 3-D rendered images used in diagnosis, surgical planning, and radiotherapeutic treatment.

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Operating Status and Improvement Plans of Ten Wetlands Constructed in Dam Reservoirs in Korea (국내 10개 댐저수지 인공습지의 운영현황 및 개선방안)

  • Choi, Kwangsoon;Kim, Sea Won;Kim, Dong Sup;Lee, Yosang
    • Journal of Wetlands Research
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    • v.16 no.3
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    • pp.431-440
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    • 2014
  • To propose the improvement and management plans to strengthen the pollutant removal efficiency of dam reservoir's constructed wetlands(CWs), the operation status and configuration of CWs (including water depth, operational flow, water flow distribution, residence time, and pollutant removal efficiency, aspect ratio, open water/vegetation ratio etc.) were analyzed in 10 major wetlands constructed in dam reservoirs. The pollutant concentrations in the inflows of the studied CWs were lower than those of American and European constructed wetlands. Especially, organic matter concentrations in all of inflows were below 3 mg/L(as BOD) due to advanced treatment of sewage disposal plant and an intake of low concentration water during dry and normal seasons. The average removal efficiency of total nitrogen(TN) and total phosphorus(TP) for 10 CWs ranged from 7.6~67.6%(mean 24.9%) and -4.9~74.5%(mean 23.7%), respectively, showing high in wetlands treating municipal wastewater. On the other hand, the removal efficiency of BOD was generally low or negative with ranging from -133.3 to 41.7%. From the analysis of the operation status and configuration of CWs, it is suggested that the low removal efficiency of dam reservoir's CWs were caused by both structural (inappropriate aspect ratio, excessive open water area) and operational (neglecting water-level management, lack of facilities and operation for first flush treatment, lake of monitoring during rainy events) problems. Therefore, to enable to play a role as a reduction facility of non-point source(NPS) pollutants, an appropriate design and operation manuals for dam reservoir's CW is urgently needed. In addition, the monitoring during rainy events, when NPS runoff occur, must be included in operation manual of CW, and then the data obtained from the monitoring is considered in estimation of the pollutant removal efficiency by dam reservoir's CW.

Beginning of the Meteorological Satellite: The First Meteorological Satellite TIROS (기상위성의 태동: 최초의 기상위성 TIROS)

  • Ahn, Myoung-Hwan
    • Atmosphere
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    • v.22 no.4
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    • pp.489-497
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    • 2012
  • Recently released a top secret document explicitly shows that the early development plan for an earth observation satellite in the USA has a hidden and more important purpose for a concept of 'free space' than the scientific purpose. At that time, the hidden and secret concept imbedded within the early space development plan prevail other national policies of the USA government for purpose of the national security. Under these circumstances, it is quite reasonable to accept a possibility that the meteorological satellites which play a key role in the every area of meteorology and climatology was also born for the hidden purposes. Even it is so, it is quite amazing that the first meteorological satellite is launched in the USA despite of the facts that the major users of the meteorological satellites were not very enthusiastic with the meteorological satellite and the program was not started as a formal meteorological satellite project. This was only possible because of the external socio-political impact caused by the successful launch of the Russian Sputnik satellite and a few key policy developers who favored the meteorological satellite program. It is also interesting to note that the beginning of the first Korean meteorological satellite program was initiated by a similar socio-political influence occurred by the launch of a North Korean satellite.

Analyzing animation techniques used in webtoons and their potential issues (웹툰 연출의 애니메이션 기법활용과 문제점 분석)

  • Kim, Yu-mi
    • Cartoon and Animation Studies
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    • s.46
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    • pp.85-106
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    • 2017
  • With the media's shift into the digital era in the 2000s, comic book publishers attempted a transition into the new medium by establishing a distribution structure using internet networks. But that effort shied from escaping the parallel-page reading structure of traditional comics. On the other hand, webtoons are showing divers changes by redesigning the structure of traditional sequential art media; they tend to separate and allot spaces according to the vertical scroll reading method of the internet browser and include animations, sound effects and background music. This trend is also in accordance with the preferences of modern readers. Modern society has complicated social structures with the development of various media; the public is therefore exposed to different stimuli and shows characteristics of differentiated perceptions. In other words, webtoons display more relevant and entertaining characteristics by inserting sounds and using moving texts and characters in specific frames, while traditional comics require an appreciation of withdrawal and immersion like other published media. Motions in webtoons are partially applied for dramatic tension or to create an effective expression of action. For example, hand-drawn animation is adopted to express motions by dividing motion images into many layers. Sounds are also utilized, such as background music with episode-related lyrics, melodies, ambient sounds and motion-related sound effects. In addition, webtoons provide readers with new amusement by giving tactile stimuli via the vibration of a smart phone. As stated above, the vertical direction, time-based nature of animation motions and tactile stimuli used in webtoons are differentiated from published comics. However, webtoons' utilization of innovative techniques hasn't yet reached its full potential. In addition to the fact that the software used for webtoon effects is operationally complex, this is a transitional phenomenon since there is still a lack of technical understanding of animation and sound application amongst the general public. For example, a sound might be programmed to play when a specific frame scrolls into view on the monitor, but the frame may be scrolled faster or slower than the author intended; in this case, sound can end before or after a reader sees the whole image. The motion of each frame is also programmed to start in a similar fashion. Therefore, a reader's scroll speed is related to the motion's speed. For this reason, motions might miss the intended timing and be unnatural because they are played out of context. Also, finished sound effects can disturb the concentration of readers. These problems come from a shortage of continuity; to solve these, naturally activated consecutive sounds or animations, like the simple rotation of joints when a character moves, is required.

Analysis and Prediction of Sewage Components of Urban Wastewater Treatment Plant Using Neural Network (대도시 하수종말처리장 유입 하수의 성상 평가와 인공신경망을 이용한 구성성분 농도 예측)

  • Jeong, Hyeong-Seok;Lee, Sang-Hyung;Shin, Hang-Sik;Song, Eui-Yeol
    • Journal of Korean Society of Environmental Engineers
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    • v.28 no.3
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    • pp.308-315
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    • 2006
  • Since sewage characteristics are the most important factors that can affect the biological reactions in wastewater treatment plants, a detailed understanding on the characteristics and on-line measurement techniques of the influent sewage would play an important role in determining the appropriate control strategies. In this study, samples were taken at two hour intervals during 51 days from $1^{st}$ October to $21^{st}$ November 2005 from the influent gate of sewage treatment plant. Then the characteristics of sewage were investigated. It was found that the daily values of flow rate and concentrations of sewage components showed a defined profile. The highest and lowest peak values were observed during $11:00{\sim}13:00$ hours and $05:00{\sim}07:00$ hours, respectively. Also, it was shown that the concentrations of sewage components were strongly correlated with the absorbance measured at 300 nm of UV. Therefore, the objective of the paper is to develop on-line estimation technique of the concentration of each component in the sewage using accumulated profiles of sewage, absorbance, and flow rate which can be measured in real time. As a first step, regression analysis was performed using the absorbance and component concentration data. Then a neural network trained with the input of influent flow rate, absorbance, and inflow duration was used. Both methods showed remarkable accuracy in predicting the resulting concentrations of the individual components of the sewage. In case of using the neural network, the predicted value md of the measurement were 19.3 and 14.4 for TSS, 26.7 and 25.1 for TCOD, 5.4 and 4.1 for TN, and for TP, 0.45 to 0.39, respectively.

The effect of resistance exercise on β-amyloid metabolism and cognitive function in a mouse model of Alzheimer's disease (저항성 운동이 알츠하이머 형질전환 생쥐 뇌의 베타 아밀로이드 대사와 인지기능에 미치는 영향)

  • Jang, Yong-Chul;Koo, Jung-Hoon
    • Journal of the Korean Applied Science and Technology
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    • v.37 no.3
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    • pp.418-428
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    • 2020
  • The aim of this study was to investigate the effect of resistance exercise(RE) on beta-amyloid(Aβ) metabolism, neuronal cell death, and cognitive function in the transgenic mice model of Alzheimer's disease(AD). Fourteen transgenic(tg) mice and fourteen non-transgenic(non-tg) mice were divided into four groups: (1)non-tg-control(NTC, n=7) (2)non-tg-RE(NTRE, n=7) (3)tg-control(TC, n=7), and (4)tg-RE(TRE, n=7). The groups with RE were performed to progressive RE on ladder equipment for 8 weeks. The groups with RE were performed to progressive RE on ladder equipment for 8 weeks. After then, the cognitive function was measured by using the water maze test, and Aβ metabolism-related proteins, neuronal cell death, and SIRT1/PGC-1α pathway were also measured. Here, we found escape latency and time were significantly increased in the TC compared to the NTC group, but it was significantly reduced in the TRE group, indicating RE may ameliorate cognitive dysfunction. Next, we found an increased in Aβ protein of TC compared to NTC, but it was significantly reduced in the TRE group following RE. In neuronal cell death, Bcl-2 was also significantly decreased and Bax was significantly increased in the TC compared to the NTC group, but RE can increase Bcl-2 and reduce Bax, which may elevate the ratio of Bcl-2/Bax. We further found a decrease in the level of ADAM10 and RARβ protein was significantly increased whereas increased in ROCK1 and BACE1 expression level was significantly reduced following RE in the TRE compared to the TC group. In addition, the level of SIRT1/PGC-1α proteins was decreased in the TC group compared to NTC group, but, these markers were significantly increased in the TRE group following RE. Therefore, our finding indicated that RE may ameliorate cognitive deficits by reducing Aβ protein and neuronal cell death via regulating SIRT1/PGC-1α, amyloidogenic pathway, and non-amyloidogenic pathway, which may play a role in an effective strategy for AD.

The Effects of Vitamin C on Lipid Contents and Fatty Acid Compositions of Serum and Liver in Rats Treated with Radiation or Aflatoxin B1 (Vitamin C가 방사선과 Aflatoxin B1을 투여한 흰쥐의 혈청과 간장의 지질성분 및 지방산 조성에 미치는 영향)

  • Kang, Jin-Soon;Kim, So-Young;Kim, Hee-Suk;Cho, Heung-Lae;Chai, Gyu-Young;Chung, Duck-Hwa
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.2
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    • pp.163-173
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    • 2007
  • Lipid peroxidation is one of the main manifestations of oxidative damage and has been found to play an important role in the toxicity and carcinogenesis of many carcinogens. This study was carried out to determine the effects of vitamin C on lipid contents and fatty acid compositions of serum and liver in male rats treated with radiation or aflatoxin $B_1\;(AFB_1)$. Six week-old male Sprague-Dawley rats were randomly divided into 7 groups; control group, radiation exposed group, $AFB_1$ treated group, X-ray and $AFB_1$ co-treated group. Three groups, except control group, were each further divided into vitamin C administered group and not administered groups. For this study, vitamin C was injected with 10 mg/kg of body weight by intraperitoneal injection and 1 hr later, 0.4 mg/kg of $AFB_1$ was injected by the same method. These administrations were repeated every 3 days over a period of 15 days. Only one time, X-ray was irradiated on whole liver with 1,500 cGy. Then vitamin C and AFB1 were administered by the same level and same method described above. On the 16th day of treatments, the animals were sacrificed. From the analysis of the serum lipid patterns, significant decrease (p<0.01) in triglyceride (TG) and total cholesterol levels were observed in X-ray and $AFB_1$ co treated group administered with vitamin C (group 7). In liver lipids, the levels of free cholesterol and total cholesterol were also decreased in X-ray and $AFB_1$ co treated group administered with vitamin C (group 7). The levels of serum free cholesterol and hepatic TG were not significantly different among all groups according to vitamin C administrations. The high density lipoprotein (HDL)-cholesterol level of serum was significantly (p<0.01) increased while the low density lipoprotein (LDL)-cholesterol level was decreased in X-ray and $AFB_1$ co treated group administered with vitamin C (group 7). In the phospholipid fatty-acid compositions of serum and liver tissue, group 3, 5 and 7 showed an increase in polyunsaturated fatty-acid (PUFA) but a decrease in saturated fatty acid (SFA) when compared to the control group. The composition ratio of fatty acid varied according to vitamin C administration. These results suggested that vitamin C has partly suppressive effects on lipid contents and fatty acid composition of serum and liver in rats treated by radiation and $AFB_1$.