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Plasma Activity of Lysosomal Enzymes in Active Pulmonary Tuberculosis (활동성 폐결핵 환자에서 혈중 리소솜 효소의 활성도)

  • Koh, Youn-Suck;Choi, Jeong-Eun;Kim, Mi-Kyung;Lim, Chae-Man;Kim, Woo-Sung;Chi, Hyun-Sook;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.5
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    • pp.646-653
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    • 1995
  • Background: The confirmative diagnosis of pulmonary tuberculosis(Tb) can be made by the isolation of Mycobacterium Tuberculosis(MTb) in the culture of the sputum, respiratory secretions or tissues of the patients, but positive result could not always be obtained in pulmonary Tb cases. Although there are many indirect ways of the diagnosis of Tb, clinicians still experience the difficulty in the diagnosis of Tb because each method has its own limitation. Therefore development of a new diagnostic tool is clinically urgent. It was reported that silica cause some lysosomal enzymes to be released from macrophages in vitro and one of these enzymes is elevated in workers exposed to silica dust and in silicotic subjects. In pulmonary Tb, alveolar macrophages are known to be activated after ingestion of MTb. Activated macrophages can kill MTb through oxygen free radical species and digestive enzymes of lysosome. But if macrophages allow the bacilli to grow intracellularly, the macrophages will die finally and local lesion will enlarge. Then it is assumed that the lysosomal enzymes would be released from the dead macrophages. The goal of this investigation was to determine if there are differences in the plasma activities of lysosomal enzymes, ($\beta$-glucuronidase(GLU) and $\beta$-N-acetyl glucosaminidase(NAG), among the groups of active and inactive pulmonary Tb and healthy control, and to see if there is any possibility that the plasma activity of GLU and NAG can be used as diagnostic indicies of active pulmonary Tb. Methods: The plasma were obtained from 20 patients with bacteriologically proven active pulmonary Tb, 15 persons with inactive Tb and 20 normal controls. In 10 patients with active pulmonary Tb, serial samples after 2 months of anti-Tb medications were obtained. Plasma GLU and NAG activities were measured by the fluorometric methods using 4-methylumbelliferyl substrates. All data are expressed as the mean $\pm$ the standard error of the mean. Results: The activites of GLU and NAG in plasma of the patients with active Tb were $21.52{\pm}3.01$ and $325.4{\pm}23.37$(nmol product/h/ml of plasma), respectively. Those of inactive pulmonary Tb were $24.87{\pm}3.78$, $362.36{\pm}33.92$ and those of healthy control were $25.45{\pm}4.05$, $324.44{\pm}28.66$(nmol product/h/ml of plasma), respectively. There were no significant differences in the plasma activities of both enzymes among 3 groups. The plasma activities of GLU at 2 months after anti-Tb medications were increased($42.18{\pm}5.94$ nmol product/h/ml of plasma) in the patients with active pulmonary Tb compared with that at the diagnosis of Tb(P-value <0.05). Conclusion: The results of the present investigation suggest that the measurement of the plasma activities of GLU and NAG in the patients with active pulmonary Tb could not be a useful method for the diagnosis of active Tb. Further investigation is necessary to define the reasons why the plasma activities of the GLU was increased in the patients with active pulmonary Tb after Tb therapy.

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A survey on the nutrient intake and food consumption of the students at the dormitories, College of Agriculture, Seoul National University (서울대학교(大學校) 농과대학(農科大學) 남녀(男女) 기숙사생(寄宿舍生)의 영양섭취(營養攝取) 조사(調査))

  • Mo, Su-Mi;Han, In-Kyu;Kim, Ze-Uook;Lee, Chun-Yung;Kim, Ho-Sik
    • Applied Biological Chemistry
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    • v.7
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    • pp.92-104
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    • 1966
  • For the purpose of the better dietary management and to empahsize of importance in nutrition education for 552 students at the dormitories, College of Agriculture, Seoul National University, the dietary survey was conducted for each consecutive seven days, from March 7th to 13th at the boy's dormitory, from March 14th to 20th at the girl's dormitory, respectively. In comparison the average caloric and nutrient intake per caput per day at the both, girl's and boy's dormitory with the recommended dietary allowances for age of 25, the intake of calories and all nutrients except riboflavin were over the allowances for the boy, while the caloric intake by the girl was considerablly below the allowance. But it is meant that only 150 calories was actually deficient in comparison with the figure of the average energy consumption determined for the girls at the dormitory of the Sook-myung Woman's University, whose pattern of living was quite similar to those of the girls at this college. Except iron and ascorbic acid, all other nutrients were deficient for the girls. The calories in the form of protein of a diet taken by the boy was 12.9% and that by the girl was 12.8%. Protein quality of the diet taken by boy scored 70 while that by the girl scored 79. NDp Cal% of the diet taken by the boy was 7 and that by the girl was figured out to be 8. Therefore, calculated reference protein taken by the boy was 55.8 grams and that by the girl was 36.9%. Though it is generally recommended that at least 1/3 of the protein should come from animal sources, it was apparent by this survey that providing 1/5 of the protein from animal sources with remaining part of high quality vegetable protein foods in the adequate mixed diet would give satisfactory results for both girl and boy students. This was clearly demonstrated by the recommended reference protein and NDp Cal% met. Significant difference between boys and girls in the average consumption of seasonings was found. In consumption per day of seasonings, boy used 1.5 grams of red pepper powder which means they used 15 times more of red pepper than girls did. Kochujang was used 13 grams by boy-students which was as high as 21 times of that of the girl. Total salt intake by the boy was 34 grams while the girl consummed 23 grams. It is obviously recognized that boys prefer more peppery and salty flavor than girls do. To reduce the amount of protein consummed and to improve the quality of protein food, increase of riboflavin rich food and increase of fat intake in place of grain intake are recommendable to the boy. For the girl's diet, consumption of grains, particularly more intake of barley mal· be recommendable to meet the B group of vitamins allowances as well as the caloric allowance. The use of more servings of yellow green vegetables is needed to the girl.

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Development of the Accident Prediction Model for Enlisted Men through an Integrated Approach to Datamining and Textmining (데이터 마이닝과 텍스트 마이닝의 통합적 접근을 통한 병사 사고예측 모델 개발)

  • Yoon, Seungjin;Kim, Suhwan;Shin, Kyungshik
    • Journal of Intelligence and Information Systems
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    • v.21 no.3
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    • pp.1-17
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    • 2015
  • In this paper, we report what we have observed with regards to a prediction model for the military based on enlisted men's internal(cumulative records) and external data(SNS data). This work is significant in the military's efforts to supervise them. In spite of their effort, many commanders have failed to prevent accidents by their subordinates. One of the important duties of officers' work is to take care of their subordinates in prevention unexpected accidents. However, it is hard to prevent accidents so we must attempt to determine a proper method. Our motivation for presenting this paper is to mate it possible to predict accidents using enlisted men's internal and external data. The biggest issue facing the military is the occurrence of accidents by enlisted men related to maladjustment and the relaxation of military discipline. The core method of preventing accidents by soldiers is to identify problems and manage them quickly. Commanders predict accidents by interviewing their soldiers and observing their surroundings. It requires considerable time and effort and results in a significant difference depending on the capabilities of the commanders. In this paper, we seek to predict accidents with objective data which can easily be obtained. Recently, records of enlisted men as well as SNS communication between commanders and soldiers, make it possible to predict and prevent accidents. This paper concerns the application of data mining to identify their interests, predict accidents and make use of internal and external data (SNS). We propose both a topic analysis and decision tree method. The study is conducted in two steps. First, topic analysis is conducted through the SNS of enlisted men. Second, the decision tree method is used to analyze the internal data with the results of the first analysis. The dependent variable for these analysis is the presence of any accidents. In order to analyze their SNS, we require tools such as text mining and topic analysis. We used SAS Enterprise Miner 12.1, which provides a text miner module. Our approach for finding their interests is composed of three main phases; collecting, topic analysis, and converting topic analysis results into points for using independent variables. In the first phase, we collect enlisted men's SNS data by commender's ID. After gathering unstructured SNS data, the topic analysis phase extracts issues from them. For simplicity, 5 topics(vacation, friends, stress, training, and sports) are extracted from 20,000 articles. In the third phase, using these 5 topics, we quantify them as personal points. After quantifying their topic, we include these results in independent variables which are composed of 15 internal data sets. Then, we make two decision trees. The first tree is composed of their internal data only. The second tree is composed of their external data(SNS) as well as their internal data. After that, we compare the results of misclassification from SAS E-miner. The first model's misclassification is 12.1%. On the other hand, second model's misclassification is 7.8%. This method predicts accidents with an accuracy of approximately 92%. The gap of the two models is 4.3%. Finally, we test if the difference between them is meaningful or not, using the McNemar test. The result of test is considered relevant.(p-value : 0.0003) This study has two limitations. First, the results of the experiments cannot be generalized, mainly because the experiment is limited to a small number of enlisted men's data. Additionally, various independent variables used in the decision tree model are used as categorical variables instead of continuous variables. So it suffers a loss of information. In spite of extensive efforts to provide prediction models for the military, commanders' predictions are accurate only when they have sufficient data about their subordinates. Our proposed methodology can provide support to decision-making in the military. This study is expected to contribute to the prevention of accidents in the military based on scientific analysis of enlisted men and proper management of them.

Assessment of Inorganic Nutrients Contents of Seasonal Foods in Seoul (계절별 다소비식품 중 무기영양원소 함량 평가)

  • Lee, Kyeong-Ah;Jang, Mi-Ra;Kim, Ouk-Hee;Park, Young-Ae;Choi, Bu-Chuhl;Han, Sung-Hee;Kim, Li-La;Kim, Jin-Kyeong;Lee, Jib-Ho;Hwang, In-Sook;Oh, Young-Hee;Jung, Kweon
    • Journal of Food Hygiene and Safety
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    • v.32 no.2
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    • pp.123-128
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    • 2017
  • The purpose of this study was to determine the sodium (Na) and potassium (K) content of seasonal foods Four hundred food samples classified into 8 different kinds of seasonal foods were collected from 150 restaurants located in Seoul. The Na and K content in seasonal foods were the analyzed by ICP-OES. The Average content of Na and K in spicy seafood noodle soup were highest as $391.4{\pm}72.7mg$/100 g and $88.6{\pm}21.4mg$/100 g, respectly, while average content of Na was lowest in spicy buckwheat noodles as $255.3{\pm}67.0mg$/ 100 g and the average content of K was lowest in Udon as $36.3{\pm}17.8mg$/ 100 g, respectively. The Na/K ratio of spicy buckwheat noodles was $3.2{\pm}1.0$, while those of cold buckwheat noodles, fish cake, Udon were very high as measured more than 8. Among the seasonal foods, the average content of Na was highest in Winter group as $366.9{\pm}81.8mg$/ 100 g and the average content of K was highest in Autumn group as $84.8{\pm}24.1mg$/ 100 g. The ratio of Na/K was lowest in Summer group as $5.9{\pm}3.3$.

The Benefit of KT-2000 Knee Ligament Arthrometer in Diagnosis of Anterior Cruciate Ligament Injury (슬관절 전방 십자 인대 파열의 진단에 있어서 KT-2000 기기의 유용성)

  • Park, Jai-Hyung;Kim, Hyoung-Soo;Jung, Kwang-Gyu;Yoo, Jeong-Hyun
    • Journal of the Korean Arthroscopy Society
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    • v.8 no.2
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    • pp.82-88
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    • 2004
  • Purpose: In this study, we intended to ascertain the benefit of KT-2000 Knee arthrometer(KT-2000) in the diagnosis of ACL(Anterior cruciate ligament) injury by comparing the anterior displacement of normal knee with that of ACL deficient knee. Materials and Methods: We designated two examiners to measure the anterior displacement of the knee joint of 30 healthy individuals, using KT-2000, at 30$^{\circ}$ flexion setting of muscle full relaxation, contraction, 25$^{\circ}$ internal rotation and 25$^{\circ}$ external rotation and analyzed these results according to the variables and measured the preoperative anterior displacement of the ACL injured knee in the 30 patients who have gone through an arthroscopic ACL reconstruction later. Results: The results of examiner 1 are 6.5${\pm}$1.5 mm, 2.5${\pm}$0.9 mm, 4.8${\pm}$1.2 mm, 6.4${\pm}$1.3 mm in right knee and 5.6${\pm}$1.3 mm, 2.1${\pm}$0.8 mm, 4.5${\pm}$1.2 mm, 5.2${\pm}$1.3 mm in left knee, in order of muscle full relaxation, contraction, 25$^{\circ}$ internal rotation and 25$^{\circ}$ external rotation. The results of examiner 2 are 6.9${\pm}$1.2mm, 2.9${\pm}$1.1mm, 5.6${\pm}$1.6mm, 6.9${\pm}$1.5mm in right, 5.5${\pm}$1.7 mm,1.9${\pm}$0.9 mm, 5.1${\pm}$1.9 mm, 5.7${\pm}$1.6 mm in left knee, The side to side difference of examiner 1 in the setting of muscle relaxation is 0.9${\pm}$1.0 mm. The anterior displaement of ACL injured knee is average 11${\pm}$2.93 mm and difference of average 6.5${\pm}$2.31 mm form that of normal. In comparison between the right and left knees of healthy individuals, the both results of two examiners showed the statistical difference in the setting of muscle full relaxation but, the results showed the side to side difference below 2 mm in 25case(83%), 21case(70%) respectively and above 3 mm in just 1 case. In the comparison between the normal and ACL injured knees, the results show the statistical difference of the side to side difference in the setting of muscle relaxation(p<0.05). Conclusion: The KT-2000 result is affected by relaxation of muscles around knee, flexion angle of knee joint, rotation of tibia, the strength of displacing force, time of the test and physical factors as height and weight. However, the Accuracy of diagnosis of ACL injury by KT-2000 will increase if the examiner is skillful and the tests are made on the exact position of knee joint.

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Comparison of One-day and Two-day Protocol of $^{11}C$-Acetate and $^{18}F$-FDG Scan in Hepatoma (간암환자에 있어서 $^{11}C$-Acetate와 $^{18}F$-FDG PET/CT 검사의 당일 검사법과 양일 검사법의 비교)

  • Kang, Sin-Chang;Park, Hoon-Hee;Kim, Jung-Yul;Lim, Han-Sang;Kim, Jae-Sam;Lee, Chang-Ho
    • The Korean Journal of Nuclear Medicine Technology
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    • v.14 no.2
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    • pp.3-8
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    • 2010
  • Purpose: $^{11}C$-Acetate PET/CT is useful in detecting lesions that are related to livers in the human body and leads to a sensitivity of 87.3%. On the other hand, $^{18}F$-FDG PET/CT has a sensitivity of 47.3% and it has been reported that if both $^{18}F$-FDG and $^{11}C$-Acetate PET/CT are carried out together, their cumulative sensitivity is around 100%. However, the normal intake of the pancreas and the spleen in $^{11}C$-Acetate PET/CT can influence the $^{18}F$-FDG PET/CT leading to an inaccurate diagnosis. This research was aimed at the verification of the usefulness of how much influence these two radioactive medical supplies can cause on the medical images through comparative analysis between the one-day and two-day protocol. Materials and Methods: This research was carried out based on 46 patients who were diagnosed with liver cancer and have gone through the PET/CT (35 male, 11 female participants, average age: $54{\pm}10.6$ years, age range: 29-69 years). The equipment used for this test was the Biograph TruePoint40 PET/CT (Siemens Medical Systems, USA) and 21 participants who went through the one-day protocol test were first given the $^{11}C$-Acetate PET/CT and the $^{18}F$-FDG PET/CT, the latter exactly after one hour. The other 25 participants who went through the two-day protocol test were given the $^{11}C$-Acetate PET/CT on the first day and the $^{18}F$-FDG PET/CT on the next day. These two groups were then graded comparatively by assigning identical areas of interest of the pancreas and the spleen in the $^{18}F$-FDG images and by measuring the Standard Uptake Value (SUV). SPSS Ver.17 (SPSS Inc., USA) was used for statistical analysis, where statistical significance was found through the unpaired t-test. Results: After analyzing the participants' medical images from each of the two different protocol types, the average${\pm}$standard deviation of the SUV of the pancreas carried out under the two-day protocol were as follows: head $1.62{\pm}0.32$ g/mL, body $1.57{\pm}0.37$ g/mL, tail $1.49{\pm}0.33$ g/mL and the spleen $1.53{\pm}0.28$ g/mL. Whereas, the results for participants carried out under the one-day protocol were as follows: head $1.65{\pm}0.35$ g/mL, body $1.58{\pm}0.27$ g/mL, tail $1.49{\pm}0.28$ g/mL and the spleen $1.66{\pm}0.29$ g/mL. Conclusion: It was found that no statistical significant difference existed between the one-day and two-day protocol SUV in the pancreas and the spleen (p<0.05), and nothing which could be misconceived as false positive were found from the PET/CT medical image analysis. From this research, it was also found that no overestimation of the SUV occurred from the influence of $^{11}C$-Acetate on the $^{18}F$-FDG medical images where those two tests were carried out for one day. This result was supported by the statistical significance of the SUV of measurement. If $^{11}C$-Acetate becomes commercialized in the future, the diagnostic ability of liver diseases can be improved by $^{18}F$-FDG and one-day protocol. It is from this result where tests can be accomplished in one day without the interference phenomenon of the two radioactive medical supplies and furthermore, could reduce the waiting time improving customer satisfaction.

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A Study on the Dietary Behaviors, Physical Development and Nutrient Intakes in Preschool Children (학령 전 아동의 식습관, 신체 발달 및 영양 섭취상태에 관한 연구)

  • Yu, Kyeong-Hee
    • Journal of Nutrition and Health
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    • v.42 no.1
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    • pp.23-37
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    • 2009
  • The purpose of this study was to investigate the health status of preschool children using the questionnaires about dietary behaviors and anthropometric indices. And also nutritional status was investigated using questionnaires for 24-hr recall method. The study was conducted in 145 children aged 3 to 6 years and questionnaires for dietary behaviors and dietary intakes were performed by mothers of children in Ulsan. Just nine percent of children were graded as good in terms of having healthy eating habits, this means that the nutrition education for the dietary behaviors should be more focused on preschool children. With regard to the frequency of food intake, children consumed green & yellow vegetables less frequently, meanwhile consumed high protein source food (meat, egg and bean) and milk and its product more frequently. Children almost never consumed fried foods as often as 1-2 times a weak. In assessment of the health status, children have the highest prevalence of colds and allergy, but lower prevalence of clinical symptoms due to the nutritional deficiency. The mean height was $103.6\;{\pm}\;6.4\;cm$ and significantly different among age (p < 0.05), but was not significantly different between sex. The mean weight was $17.8\;{\pm}\;3.0\;kg$ and significantly different in 5, 6years old among age. By the WLI criteria, 11.1% of children were underweight and 17.4% of children were overweight or obese. By the Rohrer index criteria, any children were not underweight and 86.8% of children were overweight or obese. By the Kaup index criteria, 2.8% of children were underweight and 29.2% of children were overweight or obese. And Obesity Index criteria, 2.1% of children were underweight and 20.8% of children were overweight or obese. The results of obesity rate by all criteria except Rohrer index indicated similar level, were significantly high in age 3 with all criteria, and decreased with age increased. The energy intake of children was lower than EER (Estimated Energy Requirements) of Dietary Reference Intakes for Koreans (KDRIs) by as much as 85.7%. Acceptable Macronutrient Distribution Ranges (AMDR) was 62.6:21.5:15.7 as carbohydrate:protein:lipid, so children consumed protein more, but consumed lipid less compared with those of KDRIs. Vitamin A intake was 133% of recommended intakes (RI) and calcium intake which was identified as the nutrient most likely to be lacking in diets was 98.9% of RI. The intakes of all minerals and vitamins except folate were higher than KDRIs. 33.3% of children were distributed in insufficiency of energy intake, 42.7% of children were distributed in insufficiency of lipid intake. These results indicate that the need of developing of nutrition education program and further concern of a public health center, university and children care center about dietary life for preschool children.

The Benefit of Individualized Custom Bolus in the Postmastectomy Radiation Therapy : Numerical Analysis with 3-D Treatment Planning (유방전절제술 후 방사선치료를 위한 조직보상체 개발 및 3차원 치료계획을 통한 유용성 분석)

  • Cho Jae Ho;Cho Kwang Hwan;Keum Kichang;Han Yongyih;Kim Yong Bae;Chu Sung Sil;Suh Chang Ok
    • Radiation Oncology Journal
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    • v.21 no.1
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    • pp.82-93
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    • 2003
  • Purpose : To reduce the Irradiation dose to the lungs and heart in the case of chest wail irradiation using an oppositional electron beam, we used an Individualized custom bolus, which was precisely designed to compensate for the differences In chest wall thickness. The benefits were evaluated by comparing the normal tissue complication probablilties (NTCPS) and dose statistics both with and without boluses. Materials and Methods : Boluses were made, and their effects evaluated in ten patients treated using the reverse hockey-stick technique. The electron beam energy was determined so as to administer 80% of the irradiation prescription dose to the deepest lung-chest wall border, which was usually located at the internal mammary lymph node chain. An individualized custom bolus was prepared to compensate for a chest wall thinner than the prescription depth by meticulously measuring the chest wall thickness at 1 emf intervals on the planning CT Images. A second planning CT was obtained overlying the individuailzed custom bolus for each patient's chest wall. 3-D treatment planning was peformed using ADAC-Pinnacle$^{3}$ for all patients with and without bolus. NTCPS based on 'the Lyman-Kutcher' model were analyzed and the mean, maximum, minimum doses, V$_{50}$ and V$_{95}$ for 4he heari and lungs were computed. Results .The average NTCPS in the ipsliateral lung showed a statistically significant reduction (p<0.01), from 80.2${\pm}$3.43% to 47.7${\pm}$4.61%, with the use of the individualized custom boluses. The mean lung irradiation dose to the ipsilateral iung was also significantly reduced by about 430 cGy, Trom 2757 cGy to 2,327 cGy (p<0.01). The V$_{50}$ and V$_{95}$ in the ipsilateral lung markedly decreased from the averages of 54.5 and 17.4% to 45.3 and 11.0%, respectively. The V$_{50}$ and V$_{95}$ In the heart also decreased from the averages of 16.8 and 6.1% to 9.8% and 2.2%, respectively. The NTCP In the contralateral lung and the heart were 0%, even for the cases with no bolus because of the small effective mean radiation volume values of 4.4 and 7.1%, respectively Conclusion : The use of an Individualized custom bolus in the radiotherapy of postrnastectorny chest wall reduced the NTCP of the ipsilateral lung by about 24.5 to 40.5%, which can improve the complication free cure probability of breast cancer patients.

Gene Expression Profiles in Cervical Cancer with Radiation Therapy Alone and Chemo-radiation Therapy (자궁경부암의 방사선치료 및 방사선항암화학 병용치료에 따른 유전자발현 조절양상)

  • Lee Kyu Chan;Kim Meyoung-kon;Kim Jooyoung;Hwang You Jin;Choi Myung Sun;Kim Chul Yong
    • Radiation Oncology Journal
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    • v.21 no.1
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    • pp.54-65
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    • 2003
  • Purpose : To analyze the gene expression Profiles of uterine ceulcal cancer, and its variation after radiation therapy, with or without concurrent chemotherapy, using a CDNA microarray. Materials and Methods :Sixteen patients, 8 with squamous ceil carcinomas of the uterine cervix, who were treated with radiation alone, and the other 8 treated w14h concurrent chemo-radiation, were Included in the study. Before the starling of the treatment, tumor biopsies were carried out, and the second time biopsies were peformed after a radiation dose of 16.2$\~$27 Gy. Three normal cervix tissues were used as a control group. The microarray experiments were peformed with 5 groups of the total RNAs extracted individually and then admixed as control, pre-radiation therapy alone, during-radiation therapy alone, pre-chemoradiation therapy, and during-chemoradlation therapy. The 33P-iabeled CDNAS were synthesized from the total RNAs of each group, by reverse transcription, and then they were hybridized to the CDNA microarray membrane. The gene expression of each microarrays was captured by the intensity of each spot produced by the radioactive isotopes. The pixels per spot were counted with an Arrayguage, and were exported to Microsoft Excel The data were normalized by the Z transformation, and the comparisons were peformed on the Z-ratio values calculated. Results : The expressions of 15 genes, including integrin linked kinase (ILK), CDC28 protein kinase 2, Spry 2, and ERK 3, were increased with the Z-ratio values of over 2.0 for the cervix cancer tissues compared to those for the normal controls. Those genes were involved In cell growth and proliferation, cell cycle control, or signal transduction. The expressions of the other 6 genes, Including G protein coupled receptor kinase 5, were decreased with the Z-ratio values of below -2.0. After the radiation thorapy, most of the genes, with a previously Increase expressions, represented the decreased expression profiles, and the genes, with the Z-ratio values of over 2.0, were cyclic nucleotlde gated channel and 3 Expressed sequence tags (EST). In the concurrent chemo-radiation group, the genes involved in cell growth and proliferation, cell cycle control, and signal transduction were shown to have increased expressions compared to the radiation therapy alone group. The expressions of genes involved in anglogenesis (angiopoietln-2), immune reactions (formyl peptide receptor-iike 1), and DNA repair (CAMP phosphodiesterase) were increased, however, the expression of gene involved In apoptosls (death associated protein kinase) was decreased. Conclusion : The different kinds of genes involved in the development and progression of cervical cancer were identified with the CDNA microarray, and the proposed theory is that the proliferation signal stalls with ILK, and is amplified with Spry 2 and MAPK signaling, and the cellular mitoses are Increased with the increased expression oi Cdc 2 and cell division kinases. After the radiation therapy, the expression profiles demonstrated 4he evidence of the decreased cancer cell proliferation. There was no sigificant difference in the morphological findings of cell death between the radiation therapy aione and the chemo-radiation groups In the second time biopsy specimen, however, the gene expression profiles were markedly different, and the mechanism at the molecular level needs further study.

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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