• Title/Summary/Keyword: Mechanisms

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Ethanol Extract from Cnidium monnieri (L.) Cusson Induces G1 Cell Cycle Arrest by Regulating Akt/GSK-3β/p53 Signaling Pathways in AGS Gastric Cancer Cells (AGS 위암세포에서 Akt/GSK-3β/p53 신호경로 조절을 통한 벌사상자 에탄올 추출물의 G1 Cell Cycle Arrest 유도 효과)

  • Lim, Eun Gyeong;Kim, Eun Ji;Kim, Bo Min;Kim, Sang-Yong;Ha, Sung Ho;Kim, Young Min
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.4
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    • pp.417-425
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    • 2017
  • Cnidium monnieri (L.) Cusson is distributed in China and Korea, and the fruit of C. monnieri is used as traditional Chinese medicine to treat carbuncle and pain in female genitalia. In this study, we examined the anti-proliferation and cell cycle arrest effects of ethanol extracts from C. monnieri (CME) in AGS gastric cancer cells. Our results show that CME suppressed cell proliferation and induced release of lactate dehydrogenase (LDH) in AGS cells by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and LDH assay. Cell morphology was altered by CME in a dose-dependent manner. In order to identify the cell cycle arrest effects of CME, we investigated cell cycle analysis after CME treatment. In our results, CME induced cell cycle arrest at G1 phase. Protein kinase B (Akt) plays a major role in cell survival mechanisms such as growth, division, and metastasis. Akt protein regulates various downstream proteins such as glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) and tumor protein p53 (p53). Expression levels of p-Akt, p-GSK-$3{\beta}$, p53, p21, cyclin E, and cyclin-dependent kinase 2 (CDK2) were determined by Western blot analysis. Protein levels of p-Akt, p-GSK-$3{\beta}$, and cyclin E were reduced while those of p53, p21, and p-CDK2 (T14/Y15) were elevated by CME. Moreover, treatment with CME, LY294002 (phosphoinositide 3-kinase/Akt inhibitor), BIO (GSK-$3{\beta}$ inhibitor), and Pifithrin-${\alpha}$ (p53 inhibitor) showed that cell cycle arrest effects were mediated through regulation of the Akt/GSK-$3{\beta}$/p53 signaling pathway. These results suggest that CME induces cell cycle arrest at G1 phase via the Akt/GSK-$3{\beta}$/p53 signaling pathway in AGS gastric cancer cells.

Suppression of Helicobacter pylori-induced Angiogenesis by a Gastric Proton Pump Inhibitor (Proton Pump Inhibitor에 의한 Helicobacter pylori의 혈관형성 억제효과)

  • Jin, Sung-Ho;Lee, Hwa-Young;Kim, Dong-Kyu;Cho, Yong-Kwan;Hahm, Ki-Baik;Han, Sang-Uk
    • Journal of Gastric Cancer
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    • v.5 no.3 s.19
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    • pp.191-199
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    • 2005
  • Background: Though infections of Helicobacter pylori (H. pylori) are closely associated with activation of host angiogenesis, the underlying mechanisms, as well as the strategy for its prevention, have not been identified. Here, we investigated a causal role of H. pylori infection in angiogenesis of gastric mucosa and a potent inhibitory effect of a gastric proton pump inhibitor (PPI) on the gastropathy. Materials and Methods: A comparative analysis of CD 34 expression in tissues obtained from 20 H. pylori-associated gastritis and 18 H. pylori-negative gastritis patients was performed. Expression of $HIF-1{\alpha}$ and VEGF were tested by using RT-PCR. To evaluate the direct effect of H. pylori infection on differentiation of endothelial HUVEC cells, we carried out an in vitro angiogenesis assay. Results: H. pyfori-associated gastritis tissues showed significantly higher density of $CD34^+$ blood vessels than did H. pylori-negative gastritis tissues, and the levels were well correlated with expressions of $HIF-1{\alpha}$. Conditioned media from H. pylori-infected gastric mucosal cells stimulated a tubular formation of HUVEC cells. We also found a significant inhibitory effect of PPI, an agent frequently used for H. pylori eradication, on H. pylori-induced angiogenesis. This drug effectively inhibited the phosphorylation of MAP kinase ERK1/2, which is a principal signal for H. pylori-induced angiogenesis. Conclusion: The fact that PPls can down-regulate H. pylori-induced angiogenesis suggest that anti-angiogenic treatment using PPI may be a preventive approach for H. pylori-associated carcinogenesis.

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Effects of epigallocatechin gallate on $CoCl_2-induced$ apoptosis in PC12 cells (PC12 세포에서 $CoCl_2$ 유발 세포자멸사에 대한 epigallocatechin-gallate의 역할)

  • Mo, Hyun-Chul;Choi, Nam-Ki;Kim, Seon-Mi;Kim, Won-Jae;Yang, Kyu-Ho
    • Journal of the korean academy of Pediatric Dentistry
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    • v.33 no.1
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    • pp.13-24
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    • 2006
  • Neuronal apoptotic events, consequently resulting in neuronal cell death, are occurred in hypoxic/ischemic condition. This cell death has been shown to be accompanied with the production of reactive oxygen species (ROS), which can attack cellular components such as nucleic acids, proteins and phospholipid. However, the underlying mechanisms of apoptosis induced in hypoxic/ischemic condition and its treatment methods are unsettled. Cobalt chloride $(CoCl_2)$ has been known to mimic hypoxic condition including the production of ROS. Epigallocatechin gallate (EGCG), a green tea polyphenol, has diverse pharmacologial activities in cell growth and death. This study was aimed to investigate the apoptotic mechanism by $CoCL_2$ and effects of EGCG on $CoCl_2-induced$ apoptosis in PC12 cells. Administration of $CoCl_2$ decreased cell survival in dose- and time-dependent manners and induced genomic DNA fragmentation. Treatment with $100{\mu}M$ EGCG for 30 min before PC12 cells were exposed to $150{\mu}M$ $CoCl_2$, being resulted in the cell viability and DNA fragmentation being rescued. $CoCl_2$ caused morphologic changes such as cell swelling and condensed nuclei whereas EGCG attenuated morphologic changes by $CoCl_2$. EGCG suppressed the apoptotic peak and a loss of ${\Delta}{\psi}_m$ induced by $CoCl_2$. $CoCl_2$ decreased Bcl-2 expression but Bax expression was not changed in $CoCl_2$- treated cells. EGCG attenuated the Bcl-2 underexpression by $CoCl_2$. $CoCl_2$ augumented the cytochrome c release from mitochondria into cytoplasm and increased caspase-8, -9 and caspase-3 activity a marker of the apoptotic executing stage. EGCG ameliorated the incruement in caspase-8, -9 and -3 activity, and cytochrome c release by $CoCl_2$ NAC (N-acetyl-cysteine), a scavenger of ROS, attenuated $CoCl_2-induced$ apoptosis in consistent with those of EGCG. These results suggest that $CoCl_2$ induces apoptotic cell death through both mitochondria- and death receptor-dependent pathway and EGCG has neuroprotective effects against $CoCl_2-induced$ apoptosis in PC12 cells.

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Understanding the Role of Wonderment Questions Related to Activation of Conceptual Resources in Scientific Model Construction: Focusing on Students' Epistemological Framing and Positional Framing (과학적 모형 구성 과정에서 나타난 사고 질문의 개념적 자원 활성화의 이해 -인식론적 프레이밍과 위치 짓기 프레이밍을 중심으로-)

  • Lee, Cha-Eun;Kim, Heui-Baik
    • Journal of The Korean Association For Science Education
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    • v.36 no.3
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    • pp.471-483
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    • 2016
  • The purpose of this study is to explore how students' epistemological framing and positional framing affect the role of wonderment questions related to the activation of conceptual resources and to investigate what contexts affect students' framings during scientific model construction. Four students were selected as focus group and they participated in collaborative scientific model construction of mechanisms relating to urination. According to the results, one student whose framings were "understanding phenomena" and "facilitator" asked wonderment questions, but the others whose framings were "classroom game" and "non-respondent" were not able to activate their conceptual resources. However, they were able to activate their conceptual resources when they shared the epistemological framing of "understanding phenomena" and shifted between the positional framings of "facilitator" and "respondent." Although they were able to activate their conceptual resources, these activated resources were not able to contribute to their model when they shifted to the framings of "classroom game" and "receiver." In contrast, when students constantly shared an "understanding phenomena" framing and dynamically shifted between the framings of "facilitator" and "respondent," they were able to activate various conceptual resources and develop their group model. The students' framings were affected by the contexts. These included: when students were confronted with cognitive difficulties and were not provided proper scaffolding; when the teacher played the role of answer provider and guided the activity with correctness; when there were several possible explanatory models that students could choose from; and when the teacher played the role of thought facilitator. This study contributes to supporting teaching and learning environments for productive scientific model construction.

The Settlement of Conflict in International Space Activities (우주활동에 있어서 분쟁의 해결과 예방)

  • Lee, Young-Jin
    • The Korean Journal of Air & Space Law and Policy
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    • v.25 no.1
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    • pp.159-203
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    • 2010
  • Together with the development of space science outer space law has become one of the most rapidly developing branches of international law. This reflects a general realization that these new activities must be subject to reasonable legal regulation if they are to serve the peaceful purposes of mankind without undue confusion and disorder. The exploration and use of outer space introduces many novel opportunities and dilemmas, and inspired insights are needed in the development of this new resource. In particular, the settlement of space law disputes is a relatively new discussion in international law. However, the significance of the settlement of space law disputes was acknowledged in various colloquia organized by legal academicians and practitioners around the world. Analysis of the dispute settlement provisions in space agreements plainly reveals the degree to which States persist to be mistrustful of any impingement to their sovereignty. They are reluctant to submit disputes to adjudication and binding arbitration, particularly when these provisions are negotiated between States which have dissimilar political, economic and social interests and demography. However, there is a slow but clear shift in this attitude as States realize the contemporary political, economic and technical pressures necessitating the lifting of the veil of State sovereignty. The development of an effective mechanism for the settlement of disputes arising in relation to the development of the exploration and exploitation of outer space has been the subject of global study by highly qualified publicists and international institutions. The 1972 Liability Convention is the space treaty with the most elaborate provisions for dispute settlement. However, it fails to ensure binding decisions. In this point, the 1998 Taipei Final Draft Convention may be a useful instrument for further consideration on whether an independent sectorialized dispute settlement mechanism should be established. Considering these circumstances it seemed essential to take legislative action to implement a system as comprehensive as the relevant legal framework are in the Law of the Sea and International Criminal Law mechanisms for dispute settlement and conflict avoidance from outer space activities.

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A Clinical Study of Pulmonary Tuberculosis in Diabetics (당뇨병에 동반된 폐결핵의 임상적 연구)

  • Jeong, In-Kyung;Yoo, Jee-Hong;Lee, Seon-Mee;Koh, Kwan-Pyo;Han, Min-Soo;Kang, Hong-Mo
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.705-713
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    • 1998
  • Background: An association between diabetes and tuberculosis has long been implied. The severity of diabetes appears to correlate with the degree of tuberculous activity. Methods: A retrospective chart review of 82 patients with active pulmonary tuberculosis in diabetics (DMTB) and 83 patients with active pulmonary tuberculosis in nondiabetics (Non-DMTB) admitted to the Kyung Hee Medical Center between January 1995 and December 1996 was underiaken. Results: The sex ratio of DMTB was 58 : 24, and that of Non-DMTB was 62 : 21. Male patients predominated in both groups. The highest incidence of DMTB was 6th and 7th decades and that of Non-DMTB was 3rd and 4th decades. In case which the tuberculosis developed after diagnosis of diabetes, the prevalence of pulmonary tuberculosis was the highest in diabetes for 5-10 years. On chest X-ray findings, the moderate advanced tuberculosis cases were the most common (60.9% in DMTTB and 50.6% in Non-DMTB). There was no relation between the degree of tuberculosis activity on chest x-ray(minimal, moderate, and far advanced tuberculosis) and presence of diabetes. The incidence of lower lung field tuberculosis in DMTB was significantly higher than Non-DMTB(p<0.05). The multiple lobe involvement was the predominant chest roentgenographic finding in both groups. There was no significant difference of treatment response between DMTB and Non-DMTB. There was no relationship between initial HbA1c and the severity of pulmonary tuberculosis on chest X-ray. During treatment of pulmonary tuberculosis in excellently and well controlled diabetes, the cure rate of pulmonary tuberculosis was significantly higher than the poorly controlled diabetes and the rate of treatment failure was significantly lower than poorly controlled diabetes. (p<0.05). Conclusion: Poor control of blood glucose is related with increased rate of treatment failure in pulmonary tuberculosis with diabetes mellitus. Further investigation will be needed to study the mechanisms of treatment failure in poorly controlled diabetics with pulmonary tuberculosis.

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Superoxide Dismutase Gene Expression in the Endotoxin-Treated Rat Lung (내독소에 의한 백서 폐장의 Superoxide Dismutase 유전자 발현에 관한 연구)

  • Yoo, Chul-Gyu;Suh, Gee-Young;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Kim, Keun-Youl;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.3
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    • pp.215-221
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    • 1994
  • Background: It is well known that oxygen free radicals(OFR) play a vital role in the various type of acute lung injury. Among various antioxidant defense mechanisms, the superoxide dismutases(SOD) are thought to be the first line of antioxidant defense by catalyzing the dismutation of two superoxide radicals to yield hydrogen peroxide and oxygen. Eukaryotic cells contain two types of intracellular SOD : cytosolic, dimeric copper/zinc- containing enzyme(CuZnSOD) and mitochondrial, tetrameric manganese-containing enzyme(MnSOD). The purpose of this study is to evaluate the time-dependent gene expression of MnSOD and CuZnSOD in the endotoxin-treated rats, and to compare with the manifestations of LPS-induced acute lung injury in rats. Methods: Total RNA from rat lung was isolated using single step phenol extraction 0, 1, 2, 4, 6, 12, 18, 24 hours after E. coli endotoxin injection(n=3, respectively). RNA was separated by formaldehyde-containing 1.2% agarose gels elctrophoresis, transblotted, baked, prehybridized, and hybridized with $^{32}P$-labeled cDNA probes for rat MnSOD and CuZnSOD, which were kindly donated by Dr. Ho(Duke University, Durham, NC, USA). The probes were labeled by nick translation. Blots were washed and autoradiography were quantitated using laser densitometry. Equivalent amounts of total RNA/gel were assessed by monitoring 28S and 18S rRNA. Results: Endotoxin caused a rise in steady-state MnSOD mRNA levels by 4h with peak mRNA accumulation by 6h. Continued MnSOD mRNA expression was observed at 12h. CuZnSOD mRNA expression was observed from 1h to 24h with peak levels by 18h. Conclusion: These results suggest that SOD palys an important defensive role in the endotoxin-induced acute lung injury in rats.

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Effects of Aminotriazole on Lung Toxicity of Paraquat Intoxicated Mice (Paraquat중독에 의한 폐독성에 미치는 Aminotriazole의 영향)

  • Lee, Seung-Il;An, Gi-Wan;Chung, Choon-Hae
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.3
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    • pp.222-230
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    • 1994
  • Background: Paraquat, a widely used herbicide, is extremely toxic, causing multiple organ failure in humans. Paraquat especially leads to irreversible progressive pulmonary fibrosis, which is related to oxygen free radicals. However, its biochemical mechanism is not clear. Natural mechanisms that prevent damage from oxygen free radicals include changes in glutathione level, G6PDH, superoxide dismutase(SOD), catalase, and glutathione peroxidase. The authors think catalase is closely related to paraquat toxicity in the lungs Method: The effects of 3-amino-1,2,4-triazole(aminotriazole), a catalase inhibitor, on mice administered with paraquat were investigated. We studied the effects of aminotriazole on the survival of mice administered with paraquat, by comparing life spans between the group to which paraquat had been administered and the group to which a combination of paraquat and aminotriazole had been administered. We measured glutathion level, glucose 6-phosphate dehydrogenase(G6PDH), superoxide dismutase(SOD), catalase, and glutathione peroxidase(GPx) in the lung tissue of 4 groups of mice: the control group, group A(aminotriazole injected), group B(paraquat administered), group C(paraquat and aminotriazole administered). Results: The mortality of mice administered with paraquat which were treated with aminotriazole was significantly increased compared with those of mice not treated with aminotriazole. Glutathione level in group B was decreased by 20%, a significant decrease compared with the control group. However, this level was not changed by the administration of aminotriazole(group C). The activity of G6PDH in all groups was not significantly changed compared with the control group. The activities of SOD, catalase, and glutathione peroxidase(GPx) in the lung tissue were significantly decreased by paraquat administration(group B); catalase showed the largest decrease. Catalase and GPX were significantly decreased by aminotriazole treatment in mice administered with paraquat but change in SOD activity was not significant(group C). Conclusion: Decrease in catalase activity by paraquat suggests that paraquat toxicity in the lungs is closely related to catalase activity. Paraquat toxicity in mice is enhanced by aminotriazole administration, and its result is related to the decrease of catalase activity rather than glutathione level in the lungs. Production of hydroxyl radicals, the most reactive oxygen metabolite, is accelerated due to increased hydrogen peroxide by catalase inhibition and the lung damage probably results from nonspecific tissue injury of hydroxyl radicals.

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Analysis of rpoB Gene in Rifampin-Resistant M. Tuberculosis by Direct Sequencing and Line Probe Assay (염기서열결정과 Line Probe 분석법에 의한 Rifampin내성 결핵균의 rpoB 유전자 분석)

  • Lee, Min-Ki;Kim, Yun-Seong;Lee, Hyo-Jin;Cheon, Du-Su;Yun, Sang-Myung;Park, Sam-Seok;Kim, Cheol-Min;Park, Soon-Kew
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.2
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    • pp.251-263
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    • 1997
  • Background : The emergence of multidrug-resistant strains of Mycobacterium tuberculosis presents a significant challange to the treatment and control of tuberculosis, and there is an urgent need to understand the mechanisms by which strains acquire multidrug resistance. Recent advances in molecular methods for the detection of M. tuberculosis genetic targets have approached the sensitivity of culture. Furthermore the prospect of determining resistance in mycobacteria at the nucleic acid level particulary to first-line drugs like rifampin, isoniazid has provided a glimps of the next generation of sensitivity test for M. tuberculosis. Previous studies in RMP resistant M. tuberculosis have shown that mutation in $\beta$subunit of RNA polymerase is main mechanism of resistance. Method : In this study, rpoB gene for the $\beta$subunit of RNA polymerase from M. tuberculosis of 42 cultured samples (32 were RMP resistant and 10 were sensitive cases) were isolated and characterised the mutations. Direct sequencing data were compared with the results of INNO-LiPA Line Probe Assay (LiPA, Innogenetics, Belgium), commercial RMP resistance detecting kit using reverse hybridization method. Results : All of the RMP resistant samples were revealed the presence of mutation by LiPA. In 22 samples (68.8%) out of 32 RMP resistant cases, the mutation types were confirmed by the positive signal at one of 4 mutation bands in the strip. The most frequent type was R5 (S531L) which were 17 cases (77.3%). Results of direct sequencing were identified the exact characteristics of 8 mutations which were not confirmed by LiPA. S522W type point mutation and 9 base pair deletion at codon 513~515 were new identified mutations for the first time. Conclusion : Mutations in rpoB gene is the main mechanism of RMP resistance in M. tuberculosis and LiPA is a very useful diagnostic tool for the early diagnosis of RMP resistance in M. tuberculosis.

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Dysfunction of Autonomic Nervous System in Patients with Chronic Obstructive Pulmonary Diseases (만성 폐쇄성 폐질환 환자의 자율신경 장애)

  • Shin, Kyeong-Cheol;Lee, Kwan-Ho;Park, Hye-Jung;Shin, Chang-Jin;Lee, Choong-Ki;Chung, Jin-Hong;Lee, Hyun-Woo
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.3
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    • pp.317-326
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    • 1999
  • Background: Neural control of airway function is through parasympathetic, sympathetic and non-adrenergic, non-cholinergic mechanisms. The autonomic nervous system controls the airway smooth muscle tone, mucociliary system, permeability and blood flow in the bronchial circulation and release of mediators from the mast cells and other inflammatory cells. The cardiovascular and respiratory autonomic efferent fibers have a common central origin, so altered cardiovascular autonomic reflexes could reflect the altered respiratory autonomic status. Therefore, we performed this study to assess the autonomic abnormality and determine the correlating factors of severity of autonomic neuropathy in patients with chronic obstructive pulmonary disease(COPD) using easily reproducible cardiovascular autonomic reflex function test. Method: The study included 20 patients with COPD and 20 healthy persons obtained on Health Promotion Center in Yeungnam university hospital. All the patients had history and clinical features of COPD as defined by the American Thoracic Society. Any patients with myocardial ischemia, cardiac arrythmia, hypertension, central or peripheral nervous system disease, diabetes mellitus, or any other diseases known to produce autonomic neuropathy, has excluded. The autonomic nervous system function tests included three tests evaluating the parasympathetic system and two tests evaluating the sympathetic system. And also all subjects were subjected to pulmonary function test and arterial blood gas analysis. Results: Autonomic dysfunction was more commonly associated with patients with COPD than healthy person The parasympathetic dysfunction was frequent in patient with COPD, but sympathetic dysfunction seemed preserved. The severity of parasympathetic dysfunction in patients with COPD was correlated with the degree of duration of disease, smoking, reductions in the value of $FEV_1$ and FVC, and arterial hypoxemia but no such correlation existed for age, type of COPD, $FEV_1$/FVC, or $PaCO_s$. Conclusion: There is high frequency of parasympathetic dysfunction associated with COPD and the parasympathetic abnormality in COPD is increased in proportion to severity of airway disease. In COPD, parasympathetic dysfunction probably does not the cause of disease, but it may be an effect of disease progression.

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