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Feasibility of Mixed-Energy Partial Arc VMAT Plan with Avoidance Sector for Prostate Cancer (전립선암 방사선치료 시 회피 영역을 적용한 혼합 에너지 VMAT 치료 계획의 평가)

  • Hwang, Se Ha;NA, Kyoung Su;Lee, Je Hee
    • The Journal of Korean Society for Radiation Therapy
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    • v.32
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    • pp.17-29
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    • 2020
  • Purpose: The purpose of this work was to investigate the dosimetric impact of mixed energy partial arc technique on prostate cancer VMAT. Materials and Methods: This study involved prostate only patients planned with 70Gy in 30 fractions to the planning target volume (PTV). Femoral heads, Bladder and Rectum were considered as oragan at risk (OARs). For this study, mixed energy partial arcs (MEPA) were generated with gantry angle set to 180°~230°, 310°~50° for 6MV arc and 130°~50°, 310°~230° for 15MV arc. Each arc set the avoidance sector which is gantry angle 230°~310°, 50°~130° at first arc and 50°~310° at second arc. After that, two plans were summed and were analyzed the dosimetry parameter of each structure such as Maximum dose, Mean dose, D2%, Homogeneity index (HI) and Conformity Index (CI) for PTV and Maximum dose, Mean dose, V70Gy, V50Gy, V30Gy, and V20Gy for OARs and Monitor Unit (MU) with 6MV 1 ARC, 6MV, 10MV, 15MV 2 ARC plan. Results: In MEPA, the maximum dose, mean dose and D2% were lower than 6MV 1 ARC plan(p<0.0005). However, the average difference of maximum dose was 0.24%, 0.39%, 0.60% (p<0.450, 0.321, 0.139) higher than 6MV, 10MV, 15MV 2 ARC plan, respectively and D2% was 0.42%, 0.49%, 0.59% (p<0.073, 0.087, 0.033) higher than compared plans. The average difference of mean dose was 0.09% lower than 10MV 2 ARC plan, but it is 0.27%, 0.12% (p<0.184, 0.521) higher than 6MV 2 ARC, 15MV 2 ARC plan, respectively. HI was 0.064±0.006 which is the lowest value (p<0.005, 0.357, 0.273, 0.801) among the all plans. For CI, there was no significant differences which were 1.12±0.038 in MEPA, 1.12±0.036, 1.11±0.024, 1.11±0.030, 1.12±0.027 in 6MV 1 ARC, 6MV, 10MV, 15MV 2 ARC, respectively. MEPA produced significantly lower rectum dose. Especially, V70Gy, V50Gy, V30Gy, V20Gy were 3.40, 16.79, 37.86, 48.09 that were lower than other plans. For bladder dose, V30Gy, V20Gy were lower than other plans. However, the mean dose of both femoral head were 9.69±2.93, 9.88±2.5 which were 2.8Gy~3.28Gy higher than other plans. The mean MU of MEPA were 19.53% lower than 6MV 1 ARC, 5.7% lower than 10MV 2 ARC respectively. Conclusion: This study for prostate radiotherapy demonstrated that a choice of MEPA VMAT has the potential to minimize doses to OARs and improve homogeneity to PTV at the expense of a moderate increase in maximum and mean dose to the femoral heads.

A Study on Traditional Ideology and the 'Tradition' of the Theatre company Minye in 1970s (1970년대 전통 이념과 극단 민예극장의 '전통')

  • Kim, Ki-Ran
    • Journal of Popular Narrative
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    • v.26 no.3
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    • pp.45-86
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    • 2020
  • In this article, the "modernization of the tradition" constructed on the cultural politics and the way in which it appropriated in the korean theatre in the 1970s were analyzed. It is trying to reveal its implications. It is also a work to critically review the aspects of self-censorship in the korean theatre in the 70s. To that end, we looked at the theatre company Minye Theatre, which preoccupied the traditional discussions in the 1970s by creating national dramas. Until now, the evaluation of the theatre company Minye Theatre in the 1970s has focused on the achievement on the directing of Heo Gyu, who promoted the succession and transformation of tradition. However, the traditional ideology constructed in the state-led cultural politics in the 70s and the way in which it was operated cannot be evaluated only in terms of artistic achievement. The ideology of tradition is selected according to the selective criteria of the subject to appropriate tradition. What's important is that certain objects are excluded, discarded, re-elected, re-interpreted and re-recognized in the selection process of selected traditional ideology. This is the situation in the '70s, when tradition was constantly re-recognized amid differences between the decadent and the disorder that were then designated as non-cultural, and led to a new way of appropriate. The nation-led traditional discussion of the '70s legalized the tradition with stable values, one of the its way was the national literary and artistic support. Under the banner of modernization of tradition, theatre company Minye preoccupied the discussions on the tradition and presented folk drama as a new theatre. As an alternative to the crisis of korean theatre at the time, the Minye chose the method of inheriting and transforming tradition. It is noteworthy that Heo Gyu, the representative director of the theatre company Minye, recognized the succession and transformation of traditional performance as both a calling and an experiment. For Heo Gyu, tradition was accepted as an irresistible stable value and an unquestionable calling, and as a result, his performance, filled with excessive traditional practices, became overambitious, especially when it failed to reflect the present-here reality, the repeated use of traditional expression tools resulted in skilled craftsmanship, not artistic creation. The traditional ideology of the 70s unfolds in a new aspect of appropriation in the 80s. In 1986, Son Jin-Cheok, Kim Seong-nyeo, and Yoon Mun-sik, who were key members of the theatre company Minye Theatre, left the theatre to create the theatre company Michu, and secured popularity through Madangnori(popular folk yard theatre). Son Jin-Cheok's Madangnori is overbearing through satire and humor. It gained popularity by criticizing and mocking state power. On the other hand, not only the form of traditional performance, but also the university-centered Madanggeuk movement, which appropriated on the spirit of resistance from the people to its traditional values, has rapidly grown. In the field of traditional discussions of the 70s, Madanggeuk was self-born through appropriation in which the spirit of resistance of the people is used as a traditional value. Madanggeuk as well as Michu that achieved the popularization of Madangnori cannot be discussed solely by the artistic achievement of the modernization of tradition. Critics of korean theatre in response to state-led traditional discussions in the 70s was focused only on the qualitative achievement of performing arts based on artistry. I am very sorry for that. As a result, the popular resistance of the Madanggeuk and the Madangnori were established in the 'difference' with the traditions of the theatre company Minye Theatre. Theatre company Minye Theatre was an opportunity for the modernization of tradition, but the fact that it did not continuously produce significant differences. This is the meaning and limitation of the "tradition" of the theatre company Minye Theatre in the history of korean theatre in the 1970s.

Mobility Change around Neighborhood Parks and Green Spaces before and after the Outbreak of the COVID-19 Pandemic (COVID-19 발생 전·후 생활권 공원녹지 모빌리티 변화 분석)

  • Choi, Ga yoon;Kim, Yong gook;Kwon, Oh kyu;Yoo, Ye seul
    • Journal of the Korean Institute of Landscape Architecture
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    • v.51 no.4
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    • pp.101-118
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    • 2023
  • During the COVID-19 pandemic, the utilization rate of neighborhood parks and green spaces increased significantly, and the outbreak served as an opportunity to highlight the values and functions of neighborhood parks and green spaces for urban residents. This study aims to empirically analyze how citizens' movement and the use of neighborhood parks and green spaces changed before and after COVID-19 and examine the social and spatial characteristics that affected these changes. As a research method, first, people's mobility around neighborhood parks and green spaces before and after the COVID-19 pandemic were compared using signal data from telecommunication carriers. Through the analysis of changes in residence time and movement volume, the movement characteristics of citizens after COVID-19 and changes in walking-based park visits were examined. Second, the factors affecting the mobility change in neighborhood parks and green spaces were analyzed. The social and spatial characteristics that affect citizens' visits to neighborhood parks and green spaces before and after COVID-19 were examined through correlation and multiple regression analysis. Subsequently, through cluster analysis, the types of living areas for the post-COVID era were classified from the perspective of the supply and management of neighborhood parks and green spaces services, and directions for improving neighborhood parks and green spaces by type were presented. Major research findings are as follows: First, since the outbreak of COVID-19, activities within 500m of the residence have increased. The amount of stay and walking movement increased in both 2020 and 2021, which means that the need to review the quantitative standards and attractions of neighborhood parks and green spaces has increased considering the changed scope of the walking and living area. Second, the overall number of visits to neighborhood parks and green spaces by walking has increased since the outbreak of COVID-19. The number of visits to neighborhood parks and green spaces centered on the house and the workplace increased significantly. The park green policy in the post-COVID era should be promoted by discovering underprivileged areas, focusing on areas where residential, commercial, and business facilities are concentrated, and improving neighborhood parks and green services in quantitative and qualitative terms. Third, it was found that the higher the level of park green service, the higher the amount of walking movement. It is necessary to use indicators that contribute to improving citizens' actual park green services, such as walking accessibility, rather than looking at the criteria for securing green areas. Fourth, as a result of cluster analysis, five types of neighborhood parks and green spaces were derived in response to the post-COVID era. This suggests that it is necessary to consider the socioeconomic status and characteristics of living areas and the level of park green services required in future park green policies. This study has academic and policy significance in that it has laid the basis for establishing neighborhood parks and green spaces policy in response to the post-COVID era by using various analysis methodologies such as carrier signal data analysis, GIS analysis, and statistical analysis.

Estimation of GARCH Models and Performance Analysis of Volatility Trading System using Support Vector Regression (Support Vector Regression을 이용한 GARCH 모형의 추정과 투자전략의 성과분석)

  • Kim, Sun Woong;Choi, Heung Sik
    • Journal of Intelligence and Information Systems
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    • v.23 no.2
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    • pp.107-122
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    • 2017
  • Volatility in the stock market returns is a measure of investment risk. It plays a central role in portfolio optimization, asset pricing and risk management as well as most theoretical financial models. Engle(1982) presented a pioneering paper on the stock market volatility that explains the time-variant characteristics embedded in the stock market return volatility. His model, Autoregressive Conditional Heteroscedasticity (ARCH), was generalized by Bollerslev(1986) as GARCH models. Empirical studies have shown that GARCH models describes well the fat-tailed return distributions and volatility clustering phenomenon appearing in stock prices. The parameters of the GARCH models are generally estimated by the maximum likelihood estimation (MLE) based on the standard normal density. But, since 1987 Black Monday, the stock market prices have become very complex and shown a lot of noisy terms. Recent studies start to apply artificial intelligent approach in estimating the GARCH parameters as a substitute for the MLE. The paper presents SVR-based GARCH process and compares with MLE-based GARCH process to estimate the parameters of GARCH models which are known to well forecast stock market volatility. Kernel functions used in SVR estimation process are linear, polynomial and radial. We analyzed the suggested models with KOSPI 200 Index. This index is constituted by 200 blue chip stocks listed in the Korea Exchange. We sampled KOSPI 200 daily closing values from 2010 to 2015. Sample observations are 1487 days. We used 1187 days to train the suggested GARCH models and the remaining 300 days were used as testing data. First, symmetric and asymmetric GARCH models are estimated by MLE. We forecasted KOSPI 200 Index return volatility and the statistical metric MSE shows better results for the asymmetric GARCH models such as E-GARCH or GJR-GARCH. This is consistent with the documented non-normal return distribution characteristics with fat-tail and leptokurtosis. Compared with MLE estimation process, SVR-based GARCH models outperform the MLE methodology in KOSPI 200 Index return volatility forecasting. Polynomial kernel function shows exceptionally lower forecasting accuracy. We suggested Intelligent Volatility Trading System (IVTS) that utilizes the forecasted volatility results. IVTS entry rules are as follows. If forecasted tomorrow volatility will increase then buy volatility today. If forecasted tomorrow volatility will decrease then sell volatility today. If forecasted volatility direction does not change we hold the existing buy or sell positions. IVTS is assumed to buy and sell historical volatility values. This is somewhat unreal because we cannot trade historical volatility values themselves. But our simulation results are meaningful since the Korea Exchange introduced volatility futures contract that traders can trade since November 2014. The trading systems with SVR-based GARCH models show higher returns than MLE-based GARCH in the testing period. And trading profitable percentages of MLE-based GARCH IVTS models range from 47.5% to 50.0%, trading profitable percentages of SVR-based GARCH IVTS models range from 51.8% to 59.7%. MLE-based symmetric S-GARCH shows +150.2% return and SVR-based symmetric S-GARCH shows +526.4% return. MLE-based asymmetric E-GARCH shows -72% return and SVR-based asymmetric E-GARCH shows +245.6% return. MLE-based asymmetric GJR-GARCH shows -98.7% return and SVR-based asymmetric GJR-GARCH shows +126.3% return. Linear kernel function shows higher trading returns than radial kernel function. Best performance of SVR-based IVTS is +526.4% and that of MLE-based IVTS is +150.2%. SVR-based GARCH IVTS shows higher trading frequency. This study has some limitations. Our models are solely based on SVR. Other artificial intelligence models are needed to search for better performance. We do not consider costs incurred in the trading process including brokerage commissions and slippage costs. IVTS trading performance is unreal since we use historical volatility values as trading objects. The exact forecasting of stock market volatility is essential in the real trading as well as asset pricing models. Further studies on other machine learning-based GARCH models can give better information for the stock market investors.

Efficacy of Interferon-Gamma Treatment in Bronchial Asthma (기관지천식에서 Interferon-Gamma 치료의 효과)

  • Kim, Kwan-Hyoung;Kim, Seok-Chan;Kim, Young-Kyoon;Kwon, Soon-Seog;Kim, Chi-Hong;Moon, Hwa-Sik;Song, Jung-Sup;Park, Sung-Hak;Lee, Choong-Eon;Byun, Kwang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.4
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    • pp.822-835
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    • 1997
  • Background : There have been many in vitro evidences that interleukin-4(IL-4) might be the most important cytokine inducing IgE synthesis from B-cells, and interferon-gamma(IFN-$\gamma$) might be a main cytokine antagonizing IL-4-mediated IgE synthesis. Recently some reports demonstrated that IFN-$\gamma$ might be used as a new therapeutic modality in some allergic diseases with high serum IgE level, such as atopic dermatitis or bronchial asthma. To evaluate the in vivo effect of IFN-$\gamma$ in bronchial asthma we tried a clinical study. Methods : Fifty bronchial asthmatics(serum IgE level over 200 IU/ml) who did not respond to inhaled or systemic corticosteroid treatment, and 17 healthy nonsmoking volunteers were included in this study. The CD 23 expressions of peripheral B-cells, the IL-4 activities of peripheral T-cells, the serum soluble CD23(sCD23) levels, and the superoxide anion(${O_2}^-$) generations by peripheral PMN were compared between bronchial asthmatics and normal subjects. The IL-4 activities of peripheral T-cells were analyzed by T-cell supernatant (T-sup)-induced CD23 expression from tonsil B-cells. In bronchial asthmatics the serum IgE levels and histamine $PC_{20}$ in addition to the above parameters were also compared before and after IFN-$\gamma$ treatment. IFN-$\gamma$ was administered subcutaneously with a weekly dose of 30,000 IU per kilogram of body weight for 4 weeks. Results : The ${O_2}^-$ generations by peripheral PMNs in bronchial asthmatics were higher than normal subjects($8.23{\pm}0.94$ vs $5.00{\pm}0.68\;nmol/1{\times}10^6$ cells, P<0.05), and significantly decreased after IFN-$\gamma$ treatment compared to initial values($3.69{\pm}0.88$ vs $8.61{\pm}1.53\;nmol/1{\times}10^6$ cells, P<0.05). CD23 expression of peripheral B-cells in bronchial asthmatics was higher than normal subjects($47.47{\pm}2.96%$, vs $31.62{\pm}1.92%$, P<0.05), but showed no significant change after IFN-$\gamma$ treatment. The serum sCD23 levels in bronchial asthmatics were slightly higher than normal subjects($191.04{\pm}23.3\;U/ml$ vs $162.85{\pm}4.85\;U/ml$), and 11(64.7%) of 17 patients showed a decreasing pattern in their serum sCD23 levels after IFN-$\gamma$ treatment. However the means of serum sCD23 levels were not different before and after IFN-$\gamma$ treatment. The IL-4 activities of peripheral T-cells in bronchial asthmatics were slightly higher than normal subjects($22.48{\pm}6.81%$ vs $18.90{\pm}2.43%$), and slightly increased after IFN-$\gamma$ treatment($27.90{\pm}2.56%$). Nine(60%) of 15 patients showed a decreasing pattern in their serum IgE levels after IFN-$\gamma$ treatment. And the levels of serum IgE were significantly decreased after IFN-$\gamma$ treatment compared to initial values ($658.67{\pm}120.84\;IU/ml$ vs $1394.32{\pm}314.42\;IU/ml$, P<0.05). Ten(83.3%) of 12 patients showed an improving pattern in bronchial hyperresponsiveness after IFN-$\gamma$ treatment, and the means of histamine $PC_{20}$ were significantly increased after IFN-$\gamma$ treatment compared to initial values ($1.22{\pm}0.29mg/ml$ vs $0.69{\pm}0.17mg/ml$, P<0.05). Conclusion : Our results suggest that IFN-$\gamma$ may be useful as well as safety in the treatment of bronchial asthmatics with high serum IgE level and that in vivo effects of IFN-$\gamma$ may be different from its in vitro effects on the regulations of IgE synthesis or the respiratory burst of PMN.

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The Clinical Characteristics of Lung Cancer in Patients with Idiopathic Pulmonary Fibrosis (특발성 폐섬유화증에 동반된 폐암 환자의 임상적 특정)

  • Park, Joo-Hun;Lee, Jin-Seong;Song, Koun-Sik;Shim, Tae-Sun;Lim, Chae-Man;Koh, Youn-Suck;Lee, Sang-Do;Kim, Woo-Sung;Kim, Won-Dong;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.5
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    • pp.674-684
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    • 1999
  • Background : It has been generally known that the incidence of lung cancer is higher in the patients with idopathic pumonary fibrosis (IPF) than those in general population. The reported incidence was variable from 4.8 to 43.2%. There were controversies on the most frequent cell type (squamous cell carcinoma vs. adenocarcinoma) and no study was done about the real concordance of cancer and the fibrotic lesion. And the pulmonary fibrosis may influence not only the development of cancer but also the treatment and prognosis of the cancer, but there was no report on that point. Method : Total 63 patients ($66.8{\pm}7.8$ year, M : F=61 : 2) were diagnosed as IPF combined with lung cancer (IFF-CA) at Asan Medical Center. A retrospective analysis was done about the risk factors of the lung cancer, pulmonary function test, the site of cancer(especially the relationship of the cancer with the fibrotic lesion), the histologic types, and the stage of cancer. The histologic types were compared with those of 2,660 patients with lung cancer who were diagnosed at the same institute for the same period. The effect of IPF on the treatment of the cancer was evaluated with the survival time after the detection of lung cancer. Results : The lung cancer was found in 63(22.9%) out of 281 patients with IPF. But in most of them(45 patients), lung cancer was detected at the same time with IPF and only in 18 patients, the cancer was diagnosed during the follow-up($25.2{\pm}17.7$ months) of IPF. So in our study, 6.7% of patients with IPF developed lung cancer during the course of the disease. The age ($66.8{\pm}7.84$ vs. $63.4{\pm}11.1$ years), percentage of smoker (88.9 vs. 67.2%), and the male gender (96.8 vs. 67.6%) were significantly higher in IPF-CA compared with lone IPF (p<0.05). The odds ratio of smoking was 4.7 compared with non smoking IPF controls. The lung cancer was located more frequently in the upper lobe and 55.5% was in the periphery of lung. The cancer was developed in the fibrotic lesion in 23 patients (35.9%), and in the majority of the patients, the cancer was separated from the fibrosis. The cell type of the lung cancer in IPF-CA was squamous cell carcinoma 34.9%, adenocarcinoma 30.2%, small cell carcinoma 19.0%, large cell undifferenciated carcinoma 6.3%, and others 9.5%. No significant difference in the distribution of histologic type of the lung cancer was found between IPF-CA and lone lung cancer. There was no significant difference in demographic features, cell types, location and the stage of the cancer between the group with concurrent IPF-CA and the group with cancer diagnosed during the follow up of IPF. There was a tendency (but statistically not significant : p=0.081) of higher incidence of adenocarcinoma among the cancers developed in the fibrotic area(43.5%) (F-CA) than in the cancers in non-fibrotic area (22.5%) (NF-CA). The prognosis of the patients with F-CA was poor (median survival : 4 months) compared with the patients with NF-CA (7 months, p=0.013), partly because the prevalence of severe IPF (the extent of fibrosis in HRCT 50%) was higher in F-CA group. Conclusion : These data suggest that the lung cancer in the patients with IPF has similar features to the ordinary lung cancer.

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The Three Types of Clinical Manifestation of Cow's Milk Allergy with Predominantly Intestinal Symptoms (위장관 증세 위주로 발현하는 영유아기 우유 알레르기 질환의 3가지 임상 유형에 관한 고찰)

  • Lee, Jeong-Jin;Lee, Eun-Joo;Kim, Hyun-Hee;Choi, Eun-Jin;Hwang, Jin-Bok;Han, Chang-Ho;Chung, Hai-Lee;Kwon, Young-Dae;Kim, Yong-Jin
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.3 no.1
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    • pp.30-40
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    • 2000
  • Purpose: During the first year of life, cow's milk protein is the major offender causing food allergy. Cow's milk allergy (CMA) affects 2~7% of infants, of which approximately one-half show predominantly gastrointestinal symptoms. We studied the clinical types of cow's milk allergy with predominantly gastrointestinal symptoms (CMA-GI) of childhood. Methods: The retrospective study was performed on 30 (male 22, female 8) patients who had diagnosed as CMA-GI during 2 years and 3 months from March 1995 to June 1997. Results: 1) Children with CMA-GI presented in the three types of clinical manifestation on the basis of time to reaction to milk ingestion: Quick (Q) onset (5 cases), Slow (S) onset (20 cases), Quick & Slow (Q&S) (5 cases). 2) Age on admission of the three groups was significantly different (p<0.05): (Q onset: $81.4{\pm}67.1$ days, S onset: $31.9{\pm}12.7$ days, Q&S: $366.0{\pm}65.0$ days). Although the body weight at birth was 10~95 percentile in all patients, body weight on admission was different: (Q onset: 10~50 percentile, S onset: below 10 percentile, Q&S: 10~25 percentile). S onset group was significantly different compared with other groups (p<0.05) and 90% of this one was failure to thrive below 3 percentile. 3) Peripheral leukocyte counts were as followings: (Q onset: $5,700{\sim}12,300/mm^3$, S onset: $10,000{\sim}33,400/mm^3$, Q&S: $5,200{\sim}14,900/mm^3$). Slow onset group was significantly different compared with other groups (p<0.05). Serum albumin levels on admission were as followings: (Q onset: $4.2{\pm}0.4\;g/dl$, S onset: $3.0{\pm}0.3\;g/dl$, Q&S: $4.0{\pm}0.3\;g/dl$). S onset group was significantly different compared with other groups (p<0.05) and 85% of this one was below 3.5 g/dl. 4) Although morphometrical analysis on small intestinal mucosa did not show enteropathy in Q onset and Q&S groups, all cases of S onset revealed enteropathy: 45% of this one showed subtotal villous atrophy, 55 % showed partial villous atrophy. 5) Allergic reaction test to other foods was not performed in S onset group because of ethical problem and high risk in general condition. In Q onset group, allergic reaction to one or two other foods: soy formula, weaning formula and eggs. Q&S goup revealed allergic reactions to several foods or to most of all foods except protein hydrolysate formula: eggs, potatos, some kinds of sea food, apples, carrots, beef and chicken. 6) Serum IgE level, peripheral eosinophil counts, milk RAST, soy RAST, skin test were not significantly different among groups. Conclusion: CMA-GI may present in three clinical ways on the basis of time to reaction to milk ingestion, typical clinical findings and morphologic changes in the small bowel mucosal biopsy specimens. This clinical subdivision might be helpful in diagnostic and therapeutic approaches in CMA-GI. Early suspicion is mandatory especially in S onset type because of high risks with malnutrition and enteropathy.

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Activation of NF-${\kappa}B$ in Lung Cancer Cell Lines in Basal and TNF-${\alpha}$ Stimulated States (폐암 세포에서 기저 상태와 TNF-${\alpha}$ 자극 시 NF-${\kappa}B$의 활성화)

  • HwangBo, Bin;Lee, Seung-Hee;Lee, Choon-Taek;Yoo, Chul-Gyu;Han, Sung-Koo;Shim, Young-Soo;Kim, Young-Whan
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.5
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    • pp.485-496
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    • 2002
  • Background : The NF-${\kappa}B$ transcription factors control various biological processes including the immune response, acute phase reaction and cell cycle regulation. NF-${\kappa}B$ complexes are retained in the cytoplasm in the basal state and various stimuli cause a translocation of the NF-${\kappa}B$ complexes into the nucleus where they bind to the ${\kappa}B$ elements and regulate the transcription of the target genes. Recent reports also suggest that NF-${\kappa}B$ proteins are involved in oncogenesis, tumor growth and metastasis. High expression of NF-${\kappa}B$ expression was reported in many cancer cell lines and tissues. The constitutive activation of NF-${\kappa}B$ was also reported in several cancer cell lines supporting its role in cancer development and survival. The anti-apoptotic action of NF-${\kappa}B$ is important for cancer survival. NF-${\kappa}B$ also controls the expression of several proteins that are important for cellular adhesion (ICAM-1, VCAM-1) suggesting a role in cancer metastasis. In lung cancer, high expression levels of the NF-${\kappa}B$ subunit p50 and c-Rel were reported. In fact, high expression does not mean a high activity, and the activation pattern of NF-${\kappa}B$ in lung cancer has not been reported. Materials and Methods : In this study, the NF-${\kappa}B$ nuclear binding activity in the basal and TNF-${\alpha}$ stimulated states were exmined in various lung cancer cell lines and compared with the normal bronchial epithelial cell line. Twelve lung cancer cell lines including the non-small cell and small cell lung cancer cell lines (A549, NCI-H358, NCI-H441, NCI-H552, NCI-H2009, NCI-H460, NCI-H1229, NCI-H1703, NCI-H157, NCI-H187, NCI-H417, NCI-H526) and BEAS-2B bronchial epithelial cell line were used. To evaluate the NF-${\kappa}B$ expression and DNA binding activity, western blot analysis and an electrophoretic mobility shift assay with the nuclear protein extracts. Results : The basal expressions of the p65 and p50 subunits were observed in the BEAS-2B cell line and all lung cancer cell lines except for NCI-H358 and NCI-H460. The expression levels of p65 and p50 were increased 30 minutes after stimulation with TNF-${\alpha}$ in BEAS-2B and in 10 lung cancer cell lines. In the NCI-H358 and NCI-H460 cell lines, p65 expression was not observed in the basal and stimulated states and the two p50 related protein levels were higher after stimulation with TNF-${\alpha}$ These new proteins were smaller than p50 and are thought to be variants of p50. In the basal state, NF-${\kappa}B$ was nearly activated in the BEAS-2B and all lung cancer cell lines. The DNA binding activity of the NF-${\kappa}B$ complexes was markedly higher after stimulation with TNF-${\alpha}$ In the BEAS-2B and all lung cancer cell line except for NCI-H358 and NCI-H460, the activated NF-${\kappa}B$ complex was a p65/p50 heterodimer. In the NCI-H358 and NCI-H460 lung cancer cell lines, the NF-${\kappa}B$ complex was variant of a p50/p50 homodimer. Conclusion : The NF-${\kappa}B$ activation pattern in the lung cancer cell lines and the normal bronchial epithelial cell lines was similar except for the activation of a variant of the p50/p50 homodimer in some lung cancer cell linse.

Time Course Change of Phagocytes and Proinflammatory Activities in BALF in Endotoxin-induced Acute Lung Injury (시간별 내독소 정맥주입으로 유발된 급성폐손상의 변화양상에 대한 고찰)

  • Moon, Seung-Hyug;Oh, Je-Ho;Park, Sung-Woo;NamGung, Eun-Kyung;Ki, Shin-Young;Im, Gun-Il;Jung, Sung-Whan;Kim, Hyeon-Tae;Uh, Soo-Tack;Kim, Yong-Hoon;Park, Choon-Sik;Jin, Byeng-Weon
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.2
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    • pp.360-378
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    • 1997
  • Background : Severe acute lung injury(ALI), also known as the adult respiratory distress syndrome(ARDS), is a heterogenous nature of dynamic and explosive clinical synrome that exacts a mortality of approximately 50%. Endotoxin(ETX) is an abundant component of the outer membrane of gram-negative bacteria capable of inducing severe lung injury in gram-negative sepsis and gram-negative bacterial pneumonia, which are among the most common predisposing causes of ARDS. The influx of PMNs into airway tissue is a pathological hallmark of LPS-induced lung injury. And there is a substantial evidence suggesting that cytokines are important mediators of lung injury in gram-negative sepsis. However, the kinetics of phagocytes and cytokines by an exact time sequence and their respective pathogenic importance remain to be elucidated. This study was performed to investigate the role of phagocytes and proinflammatory cytokines in ETX-induced ALI through a time course of changes in the concentration of protein, $TNF{\alpha}$ and IL-6, and counts of total and its differential cells in BALF. The consecutive histologic findings were also evaluated. Method : The experimental animals, healthy male Sprague-Dawley, weighted $200{\pm}50g$, were divided into control- and ALI- group. ALI was induced by an intravenous administration of ETX, 5mg/kg. Above mentioned all parameters were examined at 0(control), 3, 6, 24, 72 h after administration of ETX. $TNF{\alpha}$ and IL-6 cone. in BALF were measured by a bioassay. Results : The protein concentration and total leukocyte count(TC) in BALF was significantly increased at 3h compared to controls(p < 0.05). The protein conc. was significantly elavated during observation period, but TC was significantly decreased at 72h(p < 0.05 vs. 24h). There was a close relationship between TC and protein cone. in BALF(r = 0.65, p < 0.001). The PMN and monocyte count was well correlated with TC in BALF, and the correlation of PMN(r = 0.97, p < 0.001) appeared to be more meaningful than that of monocyte(r = 0.61, p < 0.001). There was also a significant correlation between protein cone. and PMN or monocyte count in BALF(PMN vs. monocyte : r = 0.55, p < 0.005 vs. r = 0.64, p < 0.001). The count of monocyte was significantly elavated during observation period though a meaningful reduction of PMN count in BALF at 72h, this observation suggested that monocyte may, at least, partipate in the process of lung injury steadly. In this study, there was no relationship between IL-6 and $TNF{\alpha}$ cone., and $TNF{\alpha}$ but not IL-6 was correlated with TC(r = 0.61, p < 0.05) and monocyte(r = 0.67, p < 0.05) in BALF only at 3, 6h after ETX introduced. In particular, the IL-6 cone. increased earlier and rapidly peaked than $TNF{\alpha}$ cone. in BALF. In histologic findings, the cell counts of lung slices were increased from 3 to 72h(p < 0.001 vs. NC). Alveolar wall-thickness was increased from 6 to 24h(p < 0.001 vs. NC). There was a significant correlation between the cell counts of lung slices and alveolar wall-thickness(r= 0.61, p < 0.001). This result suggested that the cellular infiltrations might be followed by the alterations of interstitium, and the edematous change of alveolar wall might be most rapidly recovered to its normal condition in the process of repair. Conclusion : We concluded that although the role of PMN is partly certain in ETX-induced ALI, it is somewhat inadequate to its known major impact on ALL Alveolar macrophage and/or non-immune cells such as pulmonary endothelial or epithelial cells, may be more importantly contributed to the initiation and perpetual progression of ETX-induced ALI. The IL-6 in ETX-induced ALI was independent to $TNF{\alpha}$, measured by a bioassay in BALF. The early rise in IL-6 in BALF implies multiple origins of the IL-6.

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Pharmacokinetic Study of Isoniazid and Rifampicin in Healthy Korean Volunteers (정상 한국인에서의 Isoniazid와 Rifampicin 약동학 연구)

  • Chung, Man-Pyo;Kim, Ho-Cheol;Suh, Gee-Young;Park, Jeong-Woong;Kim, Ho-Joong;Kwon, O-Jung;Rhee, Chong-H.;Han, Yong-Chol;Park, Hyo-Jung;Kim, Myoung-Min;Choi, Kyung-Eob
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.3
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    • pp.479-492
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    • 1997
  • Background : Isoniazid(INH) and rifampicin(RFP) are potent antituberculous drugs which have made tuberculous disease become decreasing. In Korea, prescribed doses of INH and RFP have been different from those recommended by American Thoracic Society. In fact they were determined by clinical experience rather than by scientific basis. Even there has been. few reports about pharmacokintic parameters of INH and RFP in healthy Koreans. Method : Oral pharmacokinetics of INH were studied in 22 healthy native Koreans after administration of 300 mg and 400mg of INH to each same person successively at least 2 weeks apart. After an overnight fast, subjects received medication and blood samples were drawn at scheduled times over a 24-hour period. Urine collection was also done for 24 hours. Pharmacokinetics of RFP were studied in 20 subjects in a same fashion with 450mg and 600mg of RFP. Plasma and urinary concentrations of INH and RFP were determined by high-performance liquid chromatography(HPLC). Results : Time to reach peak serum concentration (Tmax) of INH was $1.05{\pm}0.34\;hrs$ at 300mg dose and $0.98{\pm}0.59\;hrs$ at 400mg dose. Half-life was $2.49{\pm}0.88\;hrs$ and $2.80{\pm}0.75\;hrs$, respectively. They were not different significantly(p > 0.05). Peak serum concentration(Cmax) after administration of 400mg of INH was $7.14{\pm}1.95mcg/mL$ which was significantly higher than Cmax ($4.37{\pm}1.28mcg/mL$) by 300mg of INH(p < 0.01). Total clearance(CLtot) of INH at 300mg dose was $26.76{\pm}11.80mL/hr$. At 400mg dose it was $21.09{\pm}8.31mL/hr$ which was significantly lower(p < 0.01) than by 300mg dose. While renal clearance(CLr) was not different among two groups, nonrenal clearance(CLnr) at 400mg dose ($18.18{\pm}8.36mL/hr$) was significantly lower than CLnr ($23.71{\pm}11.52mL/hr$) by 300mg dose(p < 0.01). Tmax of RFP was $1.11{\pm}0.41\;hrs$ at 450mg dose and $1.15{\pm}0.43\;hrs$ at 600mg dose. Half-life was $4.20{\pm}0.73\;hrs$ and $4.95{\pm}2.25\;hrs$, respectively. They were not different significantly(p > 0.05). Cmax after administration of 600mg of RFP was $13.61{\pm}3.43mcg/mL$ which was significantly higher than Cmax($10.12{\pm}2.25mcg/mL$) by 450mg of RFP(p < 0.01). CLtot of RFP at 450mg dose was $7.60{\pm}1.34mL/hr$. At 600mg dose it was $7.05{\pm}1.20mL/hr$ which was significantly lower(p < 0.05) than by 450mg dose. While CLr was not different among two groups, CLnr at 600 mg dose($5.36{\pm}1.20mL/hr$) was significantly lower than CLnr($6.19{\pm}1.56mL/hr$) by 450mg dose(p < 0.01). Conclusion : Considering Cmax and CLnr, 300mg, of INH and 450mg RFP might be sufficient doses for the treatment of tuberculosis in Koreans. But it remains to be clarified in the patients with tuberculosis.

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