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Microtubule-damaging Chemotherapeutic Agent-mediated Mitotic Arrest and Apoptosis Induction in Tumor Cells (미세소관-손상 항암제 처리에 의한 세포주기의 정지 및 에폽토시스 유도)

  • Jun, Do Youn;Kim, Young Ho
    • Journal of Life Science
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    • v.26 no.3
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    • pp.376-386
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    • 2016
  • Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.

Biological Functions of N- and O-linked Oligosaccharides of Equine Chorionic Gonadotropin and Lutropin/Chorionicgonadotropin Receptor

  • Min, K. S.
    • Proceedings of the KSAR Conference
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    • 2000.10a
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    • pp.10-12
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    • 2000
  • Members of the glycoprotein family, which includes CG, LH, FSH and TSH, comprise two noncovalently linked $\alpha$- and $\beta$-subunits. Equine chorionic gonadotropin (eCG), known as PMSG, has a number of interesting and unique characteristics since it appears to be a single molecule that possesses both LH- and FSH-like activities in other species than the horse. This dual activity of eCG in heterologous species is of fundamental interest to the study of the structure-function relationships of gonadotropins and their receptors. CG and LH $\beta$ genes are different in primates. In horse, however, a single gene encodes both eCG and eLH $\beta$-subunits. The subunit mRNA levels seem to be independently regulated and their imbalance may account for differences in the quantities of $\alpha$ - and $\beta$ -subunits in the placenta and pituitary. The dual activities of eCG could be separated by removal of the N-linked oligosaccharide on the $\alpha$-subunit Asn 56 or CTP-associated O-linked oligosaccharides. The tethered-eCG was. efficiently secreted and showed similar LH-like activity to the dimeric eCG. Interestingly, the FSH-like activity of the tethered-eCG was increased markedly in comparison with the native and wild type eCG. These results also suggest that this molecular can implay particular models of FSH-like activity not LH-like activity in the eCG/indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion. A single-chain analog can also be constructed to include additional hormone-specific bioactive generating potentially efficacious compounds that have only FSH-like activity. The LH/CG receptor (LH/CGR), a membrane glycoprotein that is present on testicular Leydig cells and ovarian theca, granulosa, luteal, and interstitial cells, plays a pivotal role in the regulation of gonadal development and function in males as well as in nonpregnant and pregnant females. The LH/CGR is a member of the family of G protein-coupled receptors and its structure is predicted to consist of a large extracellular domain connected to a bundle of seven membrane-spanning a-helices. The LH/CGR phosphorylation can be induced with a phorbol ester, but not with a calcium ionophore. The truncated form of LHR also was down-regulated normally in response to hCG stimulation. In contrast, the cell lines expressing LHR-t63I or LHR-628, the two phosphorylation-negative receptor mutant, showed a delay in the early phase of hCG-induced desensitization, a complete loss of PMA-induced desensitization, and an increase in the rate of hCG-induced receptor down-regulation. These results clearly show that residues 632-653 in the C-terminal tail of the LHR are involved in PMA-induced desensitization, hCG-induced desensitization, and hCG-induced down-regulation. Recently, constitutively activating mutations of the receptor have been identified that are associated with familial male-precocious puberty. Cells expressing LHR-D556Y bind hCG with normal affinity, exhibit a 25-fold increase in basal cAMP and respond to hCG with a normal increase in cAMP accumulation. This mutation enhances the internalization of the free and agonist-occupied receptors ~2- and ~17-fold, respectively. We conclude that the state of activation of the LHR can modulate its basal and/or agonist-stimulated internalization. Since the internalization of hCG is involved in the termination of hCG actions, we suggest that the lack of responsiveness detected in cells expressing LHR-L435R is due to the fast rate of internalization of the bound hCG. This statement is supported by the finding that hCG responsiveness is restored when the cells are lysed and signal transduction is measured in a subcellular fraction (membranes) that cannot internalize the bound hormone.

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Quantitative Study of Annular Single-Crystal Brain SPECT (원형단일결정을 이용한 SPECT의 정량화 연구)

  • 김희중;김한명;소수길;봉정균;이종두
    • Progress in Medical Physics
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    • v.9 no.3
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    • pp.163-173
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    • 1998
  • Nuclear medicine emission computed tomography(ECT) can be very useful to diagnose early stage of neuronal diseases and to measure theraputic results objectively, if we can quantitate energy metabolism, blood flow, biochemical processes, or dopamine receptor and transporter using ECT. However, physical factors including attenuation, scatter, partial volume effect, noise, and reconstruction algorithm make it very difficult to quantitate independent of type of SPECT. In this study, we quantitated the effects of attenuation and scatter using brain SPECT and three-dimensional brain phantom with and without applying their correction methods. Dual energy window method was applied for scatter correction. The photopeak energy window and scatter energy window were set to 140ke${\pm}$10% and 119ke${\pm}$6% and 100% of scatter window data were subtracted from the photopeak window prior to reconstruction. The projection data were reconstructed using Butterworth filter with cutoff frequency of 0.95cycles/cm and order of 10. Attenuation correction was done by Chang's method with attenuation coefficients of 0.12/cm and 0.15/cm for the reconstruction data without scatter correction and with scatter correction, respectively. For quantitation, regions of interest (ROIs) were drawn on the three slices selected at the level of the basal ganglia. Without scatter correction, the ratios of ROI average values between basal ganglia and background with attenuation correction and without attenuation correction were 2.2 and 2.1, respectively. However, the ratios between basal ganglia and background were very similar for with and without attenuation correction. With scatter correction, the ratios of ROI average values between basal ganglia and background with attenuation correction and without attenuation correction were 2.69 and 2.64, respectively. These results indicate that the attenuation correction is necessary for the quantitation. When true ratios between basal ganglia and background were 6.58, 4.68, 1.86, the measured ratios with scatter and attenuation correction were 76%, 80%, 82% of their true ratios, respectively. The approximate 20% underestimation could be partially due to the effect of partial volume and reconstruction algorithm which we have not investigated in this study, and partially due to imperfect scatter and attenuation correction methods that we have applied in consideration of clinical applications.

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Delirium after Head Trauma at Psychiatric Consultation (두부 외상 후 섬망의 자문 정신 의학적 고찰)

  • Kim, Hyon-Chul;Lee, Sang-Chul;Kim, Do-Hoon;Lee, Sang-Kyu;Hong, Seung-Gwan;Son, Bong-Ki
    • Korean Journal of Psychosomatic Medicine
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    • v.12 no.1
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    • pp.15-22
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    • 2004
  • Objectives: Delirium after head trauma results in various cognitive and behavioral dysfunction. This study aimed at developing and validating a predicitive model for clinical improvement after delirium based on precipitating factors during hospitalization Method: Data were collected on 45 patients who developed delirium after head trauma using 5 year retrospective design, based on reviews of medical charts including psychiatric consultation reports. The differences of the group who sustained residual symptoms of delirium(The RS group) and the group of full recovery(The FR group) at 4 week follow-up visits were compared by motoric type of delirium, socio-demographic variables, neuroimaging variables and clinical variables of interest. Result: There was significant difference in reason for initial consultation between two groups, in terms of hyperactivity(p<.01). The presence of compensation claim, subcortical gray matter lesion was significantly associated with the RS group(p<.05). Total length of intensive care unit(ICU) admission and of hospital stay were significantly longer in RS group than FR group(p<.01). Conclusion: This study shows that hyperactivity on initial consultation, compensation claims, specific brain lesion were altogether significant factors in explaining prolonged duration of delirium after head trauma. A simple predictive model based on the presence of precipitating factors might be used to identify delirious patients at high risk for prolonged cognitive dysfunction. Early psychiatric intervention would be required for evaluating efficacious management and shortening admission period.

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A Study on The Performance and Fuel Economy of Diesel Vehicles According to Change in Fuel Properties (연료물성에 따른 경유 차량의 성능 및 에너지소비효율 연구)

  • Noh, Kyeong-Ha;Lee, Min-Ho;Kim, Ki-Ho;Lee, Jung-Min
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.3
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    • pp.667-675
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    • 2018
  • Increasing emissions regulations and demand of high-efficiency cars that travels a lot of distance with less fuel, there is growing interest in Energy Consumption Efficiency. Korean energy consumption efficiency compute combined Fuel Economy by driven city & highway driving mode and present final Energy Consumption Efficiency as using 5-cycle correction formula. Energy consumption efficiency is computed Carbon-balance-method, when used burning fuel play a key role in vehicle performance & Energy Consumption Efficiency. In Korea, vehicle fuel is circulate by Petroleum and Petroleum Alternative Business Act, there is property difference in quality standard because petroleum sector's refine method or type of crude oil. It does not appear a big difference according to fuel, because it sets steady quality standard, it may affect the performance of automobile. Thus, in research We purchase a few diesel fuel which circulated in the market in summer season though directly-managed-gas station by petroleum sector, resolve property each of fuel, we compute Fuel Economy each of them. We analyze into change depend on applying for property as nowadays utilizing Energy Consumption Efficiency calculating formula of gasoline and diesel fuel. As result, Density each of sample fuel has a maximum difference roughly 0.9%, net heat value each of sample fuel has difference 1.6%, result of current Energy Consumption Efficiency each of sample fuel has a difference roughly 1% at city drive mode, 1.4% at highway drive mode. Result of use gasoline calculator formula shows less 6% result than nowadays utilizing Energy Consumption Efficiency calculating formula, each of sample's Energy Consumption Efficiency shows maximum roughly 1.4% result in city & highway drive mode.

Evaluation of Chloride and Chemical Resistance of High Performance Mortar Mixed with Mineral Admixture (광물성 혼화재료를 혼입한 고성능 모르타르의 염해 및 화학저항성 평가)

  • Lee, Kyeo-Re;Han, Seung-Yeon;Choi, Sung-Yong;Yun, Kyong-Ku
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.19 no.5
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    • pp.618-625
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    • 2018
  • With the passing of time, exposed concrete structures are affected by a range of environmental, chemical, and physical factors. These factors seep into the concrete and have a deleterious influence compared to the initial performance. The importance of identifying and preventing further performance degradation due to the occurrence of deterioration has been greatly emphasized. In recent years, evaluations of the target life have attracted increasing interest. During the freezing-melting effect, a part of the concrete undergoes swelling and shrinking repeatedly. At these times, chloride ions present in seawater penetrate into the concrete, and accelerate the deterioration due to the corrosion of reinforced bars in the concrete structures. For that reason, concrete structures located onshore with a freezing-melting effect are more prone to this type of deterioration than inland structures. The aim of this study was to develop a high performance mortar mixed with a mineral admixture for the durability properties of concrete structures near sea water. In addition, experimental studies were carried out on the strength and durability of mortar. The mixing ratio of the silica fume and meta kaolin was 3, 7 and 10 %, respectively. Furthermore, the ultra-fine fly ash was mixed at 5, 10, 15, and 20%. The mortar specimens prepared by mixing the admixtures were subjected to a static strength test on the 1st and 28th days of age and degradation acceleration tests, such as the chloride ion penetration resistance test, sulfuric acid resistance test, and salt resistant test, were carried out at 28 days of age. The chloride diffusion coefficient was calculated from a series of rapid chloride penetration tests, and used to estimate the life time against corrosion due to chloride ion penetration according to the KCI, ACI, and FIB codes. The life time of mortar with 10% meta kaolin was the longest with a service life of approximately 470 years according to the KCI code.

ATHEROSCLEROSIS, CHOLESTEROL AND EGG - REVIEW -

  • Paik, I.K.;Blair, R.
    • Asian-Australasian Journal of Animal Sciences
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    • v.9 no.1
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    • pp.1-25
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    • 1996
  • The pathogenesis of atherosclerosis can not be summarized as a single process. Lipid infiltration hypothesis and endothelial injury hypothesis have been proposed and investigated. Recent developments show that there are many points of potential interactions between them and that they can actually be regarded as two phases of a single, unifying hypothesis. Among the many risk factors of atherosclerosis, plasma homocysteine and lipoprotein(a) draw a considerable interest because they are independent indicators of atherogenicity. Triglyceride (TG)-rich lipoproteins (chylomicron and VLDL) are not considered to be atherogenic but they are related to the metabolism of HDL cholesterol and indirectly related to coronary heart disease (CHD). LDL can of itself be atherogenic but the oxidative products of this lipoprotein are more detrimental. HDL cholesterol has been considered to be a favorable cholesterol. The so-called 'causalist view' claims that HDL traps excess cholesterol from cellular membranes and transfers it to TG-rich lipoproteins that are subsequently removed by hepatic receptors. In the so-called 'noncausalist view', HDL does not interfere directly with cholesterol deposition in the arterial wall but instead reflects he metabolism of TG-rich lipoproteins and their conversion to atherogenic remnants. Approximately 70-80% of the human population shows an effective feedback control mechanism in cholesterol homeostasis. Type of dietary fat has a significant effect on the lipoprotein cholesterol metabolism and atherosclerosis. Generally, saturated fatty acids elevate and PUFA lower serum cholesterol, whereas MUFA have no specific effect. EPA and DHA inhibit the synthesis of TG, VLDL and LDL, and may have favourable effects on some of the risk factors. Phospholipids, particularly lecithin, have an antiatherosclerotic effect. Essential phospholipids (EPL) may enhance the formation of polyunsaturated cholesteryl ester (CE) which is less sclerotic and more easily dispersed via enhanced hydrolysis of CE in the arterial wall. Also, neutral fecal steroid elimination may be enhanced and cholesterol absorption reduced following EPL treatment. Antioxidants protect lipoproteins from oxidation, and cells from the injury of toxic, oxidized LDL. The rationale for lowering of serum cholesterol is the strong association between elevation of plasma or serum cholesterol and CHD. Cholesterol-lowing, especially LDL cholesterol, to the target level could be achieved using diet and combination of drug therapy. Information on the link between cholesterol and CHD has decreased egg consumption by 16-25%. Some clinical studies have indicated that dietary cholesterol and egg have a significant hypercholesterolemic effect, while others have indicated no effect. These studies differed in the use of purified cholesterol or cholesterol in eggs, in the range of baseline and challenge cholesterol levels, in the quality and quantity of concomitant dietary fat, in the study population demographics and initial serum cholesterol levels, and clinical settings. Cholesterol content of eggs varies to a certain extent depending on the age, breed and diet of hens. However, egg yolk cholesterol level is very resistant to change because of the particular mechanism involved in yolk formation. Egg yolk contains a factor of factors responsible for accelerated cholesterol metabolism and excretion compared with crystalline cholesterol. One of these factors could be egg lecithin. Egg lecithin may not be as effective as soybean lecithin in lowering serum cholesterol level due probably to the differences of fatty acid composition. However, egg lecithin may have positive effects in hypercholesterolemia by increasing serum HDL level and excretion of fecal cholesterol. The association of serum cholesterol with egg consumption has been widely studied. When the basal or control diet contained little or no cholesterol, consumption of 1 or 2 eggs daily increased the concentration of plasma cholesterol, whereas that of the normolipemic persons on a normal diet was not significantly influenced by consuming 2 to 3 eggs daily. At higher levels of egg consumption, the concentration of HDL tends to increase as well as LDL. There exist hyper-and hypo-responders to dietary (egg) cholesterol. Identifying individuals in both categories would be useful from the point of view of nutrition guidelines. Dietary modification of fatty acid composition has been pursued as a viable method of modifying fat composition of eggs and adding value to eggs. In many cases beneficial effects of PUFA enriched eggs have been demonstrated. Generally, consumption of n-3 fatty acids enriched eggs lowered the concentration of plasma TG and total cholesterol compared to the consumption of regular eggs. Due to the highly oxidative nature of PUFA, stability of this fat is essential. The implication of hepatic lipid accumulation which was observed in hens fed on fish oils should be explored. Nutritional manipulations, such as supplementation with iodine, inhibitors of cholesterol biosynthesis, garlic products, amino acids and high fibre ingredients, have met a limited success in lowering egg cholesterol.

A Study on the K-REITs of Characteristic Analysis by Investment Type (K-REITs(부동산투자회사)의 투자 유형별 특성 분석)

  • Kim, Sang-Jin;Lee, Myenog-Hun
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.17 no.11
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    • pp.66-79
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    • 2016
  • A discussion has recently emerged over the increase of approvals of K-REITs, which is concluded on the basis of how to raise funds for business activity, fulfill the expected rate of return and maximize the management of managing investment funds. In addition, corporations need to acknowledge the necessity of the capital structure reflected in the current economic environment and decision-making processes. This research analyzed the characteristics by investment types and influence factors about the debt ratio of K-REITs. The data were collected from general management about business state, investment, and finance from 2002 to 2015 in K-REITs (except for the GFC period of 2007~2009). The results of the research demonstrated the high ratios of the largest shareholder characteristics, which are corporation, pension funds, mutual funds, banks, securities, insurance, and, recently, the increasing ratio of the largest shareholder and major stockholder. The investment of K-REITs is increasing the role of institutional investors that take a leading development of K-REITs. The behaviors of simultaneous investment of institutional investors were analyzed to show that they received higher interest rates than other financial institutions and ran in parallel with attraction and compensation. The results of the multiple regressions analysis, utilizing variables about debt ratio were as follows. The debt ratio showed a negative (-) relation that profitability is increasing, which matches the pecking order theory and trade off theory. On the other hand, investment opportunities (growth potential) showed a negative (-) relation and assets scale that indicated a positive (+) relation. The research results are reflected as follows. K-REITs focused on private equity REITs more than public offering REITs, and in the case of financing the capital of others, loan capital is operated under the guarantee of tangible assets (most of real estate) more than financing of the stock market. Further, after the GFC, the capital of others was actively utilized in K-REITs business, and the debt ratio showed that the determinant factors by the ratio and characteristics of the largest shareholder and investment products.

Analysis on the Policy Network in the Defense Industry Exportation Support Policy: Focusing on the Success of the T-50 Exportation to Indonesia (방산수출 지원정책에 관한 정책네트워크 연구: T-50 인도네시아 수출 성공사례를 중심으로)

  • Jun, Jongho
    • Journal of Technology Innovation
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    • v.24 no.1
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    • pp.113-142
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    • 2016
  • T-50 exportation to Indonesia embodied an objective of governmental policy and became a catalyst accelerating the exportation of domestic defense industries. Defense industry exportation is recognized as a new growth engine creating economic interests and it became an important policy of the government. This study will suggest an effective direction for the support policy of the defense industry exportation through analysis on factors behind the success of the T-50 exportation to indonesia in the view of policy network. Policy network theory has its efficacy and workability in analyzing what kind of results are yielded from each policy actor's attributes and their interaction during the execution and establishment of the support policy for the defense exportation. The type of policy network of the T-50 exportation to Indonesia was a policy community. Many governmental ministries, defense industry which is the group of interest, and experts from the research institutes have established the Korea Defense Trade Support Center(KODITS) for accomplishing common policy goal with mutually shared sentiment, and sought for a strategy for the success of the defense industry exportation having official and unofficial meeting centering around the KODITS. Although there were oppositions and conflicts among major actors, though forming a cooperative relationship among majority of the actors, policy-wise decision making for the exportation of the T-50 to Indonesia was efficiently carried out. The cooperative relationship was the key in the success of the T-50 exportation. Considering that the policy community from cooperative mutual interaction is efficient in reaching the goal of the defense industry exportation support policy, this study suggests operating government-wise temporary Task Force(TF) to succeed in big exportation projects such as the T-X exportation to the U.S. In addition, institutional and procedural supplementation such as regular meetings among the head of related governmental ministries and etc. are required in order to enhance the mutually cooperative relationship withing the TF.

Body Perception, Attitude on Weight-control and Self-Esteem according to the weight group of High School Students in Daegu (대구광역시 고등학생의 체중군에 따른 체형인식, 체중조절 태도와 자아 존중감의 비교)

  • Kim, Hae-Jeong;Jang, Hyun-Sook
    • Journal of Korean Home Economics Education Association
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    • v.21 no.2
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    • pp.1-22
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    • 2009
  • This study was to investigate of body perception, attitude on weight-control and self-esteem according to the weight group of high school students. Using the questionnaires taken by 777 first grade students in six high schools in Daegu, this study was conducted from August 20th to September 10th in 2007. Statistical data analysis were completed using the SPSS 12.0 program. The results of this study were as follows : First, girls are more interested in weight-control than boys, especially about obesity. As a result, they try to control their weight to lose weight in high school days with the right perception of weight. They also have good knowledge about weight-control and cut down the food intake. We need to study more about the reason why the self-esteem of girls' obesity group is high. Second, most of the boys controled weight for their health and they did exercise to lose weight and they are more satisfied with the result of weight-control and self-esteem than girls. About the body type, boys got affected by friends, and girls by TV. In boys' case, as the BMI is low and the difference between their present weight and ideal weight is small, they are more satisfied with the result of weight-control and prefer physical activities. In girls' case, as the BMI is low and their satisfaction with the weight-control result is high, they have good eating habit and high self-esteem. Third, compared with the weight group and their self-esteem, in boys' case, low-weight boys are high when they do physical activities more than 20 minutes, whereas when the normal-weights and over-weights are satisfied with their weight-control result, and the obese have good eating habit, it is high. In girls' case, the self-esteem is high when the normal-weights are satisfied with their weight-control result and over-weights prefer physical activities and the obese are interested in weight-control. Especially, the obese girls group show high self-esteem when they have interest in weight-control.

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