• Title/Summary/Keyword: active agents

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Induction of Apoptosis and Antitumor Activity by Stichoposide D through the Generation of Ceramide in Human Leukemia Cells (Stichoposide D의 백혈병 세포주에서 세라마이드 생성을 통한 세포 사멸 유도 및 항암 작용)

  • Park, Eun-Seon;Yun, Seung-Hoon;Shin, Sung-Won;Kwak, Jong-Young;Park, Joo-In
    • Journal of Life Science
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    • v.22 no.6
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    • pp.760-771
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    • 2012
  • Marine triterpene glycosides are physiologically active natural compounds isolated from sea cucumbers(holothurians). It was demonstrated that they have a wide range of biological activities, including antifungal, cytotoxic, and antitumor effects. A previous study showed that stichoposide C (STC) isolated from Thelenota anax induces apoptosis through generation of ceramide by activation of acid sphingomyelinase (SMase) and neutral SMase in human leukemia cells. In this study, we investigated whether STD, a structural analog of STC, can induce apoptosis and examined the molecular mechanisms for its activity. It was found that STC and STD induce apoptosis in a dose- and time-dependent manner and lead to the activation of caspase-8, mitochondrial damage, activation of caspase-9, and activation of caspase-3 in K562 and HL-60 cells. STC activates acid SMase and neutral SMase, which results in the generation of ceramide. Specific inhibition of acid SMase or neutral SMase partially blocked STC-induced apoptosis, but not STD-induced apoptosis. In contrast, STD generates ceramide through the activation of ceramide synthase. Specific inhibition of ceramide synthase partially blocked STD-induced apoptosis, but not STC-induced apoptosis. Moreover, STC and STD markedly reduced tumor growth of HL-60 xenograft tumors and increased ceramide generation in vivo. These results indicate that STC and STD can induce apoptosis and have antitumor activity through the different molecular mechanisms, because they have a different sugar residue attached to aglycones. Thus, these results suggest that their actions are affected by a sugar residue attached to aglycones and they can be used as anticancer agents in the treatment of leukemia.

Inhibition of Vascular Endothelial Growth Factor-induced Endothelial Cell Differentiation by Intravenous Immunoglobulin and Methylprednisolone (혈관내막 성장인자에 의해 유도된 내막세포 분화에 대한 정맥용 면역글로불린과 메틸프레드니솔론의 효과)

  • Choi, Hyoun Ah;Ha, Kyung Hwa;Yoon, Jong Seo;Lee, Yoon;Lee, Joon Sung;Han, Ji Wwan
    • Clinical and Experimental Pediatrics
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    • v.48 no.8
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    • pp.886-893
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    • 2005
  • Purpose : Kawasaki disease is the most common cause of systemic vasculitis in children less than 5 years of age. Recent immunohistochemistry findings suggest that many vascular growth factors play a role in the formation of the coronary artery lesions. Active remodeling of the coronary artery lesions in Kawasaki disease continues in the form of intimal proliferation and neoangiogenesis for several years after the onset of the disease. Intravenous immunoglobulin(IVIG) and corticosteroid have been used in the treatment of Kawasaki disease but the exact mechanism is not clear. We have investigated that IVIG and corticosteroid inhibited vascular endothelial growth factor(VEGF)-induced tube formation of endothelial cells in vitro on Matrigel assay. Methods : Human umbilical vein endothelial cells(HUVECs) were cultured and seeded on Matrigel coated 24 well plates in medium with or without the following agents : VEGF, VEGF plus IVIG, VEGF plus VEGF antibody, VEGF plus methylprednisolone, VEGF, IVIG plus methylprednisolone for 18 hours. The total length of tube structures in each photograph was quantified. Results : IVIG significantly inhibited the proliferation of HUVECs. The inhibitory effect of IVIG was also reversible. In the meantime, VEGF induced the differentiation of HUVECs into capillary like structures on Matrigel, which was inhibited by VEGF antibody in a dose-dependent manner. Interestingly, IVIG and methylprednisolone inhibited VEGF-induced tube formation of HUVECs. IVIG was more effective in inhibition than methylprednisolone alone. Conclusion : We revealed that VEGF induced the differentiation of HUVECs and this effect was inhibited by IVIG and methylprednisolone.

The Biological Effects of β-Cyclodextrin on Antithrombotic Activity and Plasma Lipid Metabolism in Rats (흰쥐에서 혈액지질 대사 및 항혈전작용에 관한 베타사이클로덱스트린의 생물학적 효과)

  • Park, B. S.
    • Journal of Animal Science and Technology
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    • v.45 no.2
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    • pp.199-210
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    • 2003
  • The effect of feeding a cyclic oligosaccharide, $\beta$-cyclodextrin($\beta$CD) on plasma cholesterol and triacylglyceride concentrations and on antithrombotic activity were investigated in rats fed a control chow diet, or one either high in cholesterol or in saturated fat. The bleeding time of $\beta$CD-fed groups was significantly prolonged by 293%, 157% and 218% in normal, high cholesterol and high fat diet fed groups, respectively, as compared to the control group(p<0.05). The whole blood clotting time was significantly increased by 202%, 168% and 211% in normal, high cholesterol and high fat diet fed groups as compared to control group, respectively(p<0.05). The $\beta$CD diet caused a marked decrease in plasma total lipid(TL), triacylglyceride(TAG), total cholesterol (TC) and low density lipoprotein- cholesterol (LDL-C) concentrations. The plasma TL concentration was significantly decreased by 70%, 82% and 87% in normal, high cholesterol and high fat diet fed groups as compared to the control group, respectively(p<0.05). The plasma TAG concentration was significantly decreased by 89%, 43% and 59% in normal, high cholesterol and high fat diet fed groups, respectively, as compared to the control group(p<0.05). The plasma TC concentration was significantly decreased by 28%, 62% and 36% in normal, high cholesterol and high fat diet fed groups, respectively, as compared to the control group(p<0.05). The LDL-C concentration was significantly decreased by 39%, 54% and 25% in normal, high cholesterol and high fat diet fed groups as compared to control group, respectively(p<0.05). The plasma total bile acids contents of $\beta$CD group was significantly increased by 66%, 95% and 97% in normal, high cholesterol and high fat diet fed groups as compared to control group, respectively(p<0.05). The hepatic HMG-CoA reductase activity was significantly lowered by 41% in the $\beta$CD-fed group compared to normal diet fed rats(p<0.05). The fecal steroid excretions of the $\beta$CD groups was significantly increased by 167% in normal diet fed rats(p<0.05). These results suggest that the $\beta$CD has a biological active function on antithrombotic activity and is hypolipidemic, hypotriglyceridemic and hypocholesterolimic agents. These are all effects that can help to prevent obesity and coronary heart disease in humans.

Experimental Fetal Cardiopulmonary Bypass in the Fetal Lamb Model (태아양 모델을 이용한 실험적 태아 심폐우회술)

  • 이정렬;임홍국;김원곤;김종성;최정연;김용진
    • Journal of Chest Surgery
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    • v.32 no.6
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    • pp.495-503
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    • 1999
  • Background: We tested the technical feasibility of fetal cardiac bypass and collected baseline data on the fetal hemodynamics and placental functions related to the cardiopulmonary bypass in the fetal lamb model. Material and Method: Eleven fetuses at 120 to 150 days of gestation were subjected to bypass via trans-sternal approach with a 12 G pulmonary arterial cannula and 14 to 18 F venous cannula for 30 minutes. All ewes received general anesthesia with ketamine. In all the fetuses, no anesthetic agents were used except muscle relaxant. Eight served as a group in which placenta was excluded from the extracorporeal circulation by clamping the umbilical cord during the bypass(the oxygenator group) and in the remaining three, the placenta worked as the only source of oxygen supply(the placenta group). Observations were made every 10 minute during a 30-minute bypass and 30-minute post bypass period. No prostaglandin inhibitors were used both in ewes and in fetuses. Result: Weights of the fetuses ranged from 1.9 to 5.2 kg. In the oxygenator group, means of arterial pressure, PaO2, atrial pressure, heart rate, and bypass flow rate ranged 69.8 to 82.6 mmHg, 201.7 to 220.9 mmHg, 4.1 to 4.3 mmHg, 169 to 182/min, and 140.3 to 164.0 ml/kg/min, respectively during bypass, but rapid deterioration of the fetal cardiac functions and the placental gas exchange was observed after the cessation of bypass. In the placenta group, means of arterial pressure decreased from 44.7 to 14.4 mmHg and means of PaCO2 increased from 61.9 to 129.6 mmHg during bypass. Flow rate was suboptimal(74.3 to 97.0 ml/kg/min) during bypass. All hearts fibrillated immediately after the discontinuation of bypass. Conclusion: In this study, the technical feasibility of fetal cardiopulmonary bypass was confirmed in the fetal lamb model. However, further studies with modifications of the bypass including an addition of prostaglandin inhibitor, an application of the total spinal anesthesia on the fetus, a creation of more concise bypass circuit, and a use of active pump are mandatory to improve the outcome.

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Occluding Effect of the Application of Fluoride Compounds and Desensitizers on Dentinal Tubules (불소도포 및 지각과민처치제 적용 후 상아세관 폐쇄효과와 지속력 평가)

  • Lee, Ye-Jin;Jeong, Moon-Jin;Ahn, Yong-Soon;Cheun, Su-Kyung;Jeong, Soon-Jeong;Lim, Do-Seon
    • Journal of dental hygiene science
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    • v.16 no.4
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    • pp.272-283
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    • 2016
  • This study compared and analyzed the occluding effects of fluoride compounds and desensitizers, which are commonly used in dental clinics, on dentinal tubules. This study also evaluated the persistence of the active ingredients over time by performing toothbrushing with an electric toothbrush. Thirty-five molar teeth, which had been extracted within the past 3 months from healthy people without tooth decays, amalgam fillings, or dental crowns, were divided into 4 pieces each. Of these, 135 teeth pieces were used as study specimens. These specimens were divided into a control group, an untreated group, and 5 experimental groups (acidulated fluoride gel, fluoride varnish, Gluma, Super Seal, and SE-Bond). The specimens were then subjected to toothbrushing equivalent to 1 week (140 times), 2 weeks (280 times), and 4 weeks (560 times), and the occluding effects on dentinal tubules in 3 regions of each specimen were examined under a scanning electron microscope. The fluoride varnish treated group showed the highest degree of dentinal tubule occlusion effects during the first, second, and fourth weeks of toothbrushing, with the SE-Bond treated group showing the second highest degree and the Gluma treated group showing the lowest degree. After 4 weeks of toothbrushing, the Gluma treated group and the Super Seal treated group showed the lowest degrees of dentinal tubule occlusion effects. In summary, the fluoride varnish treated group and the SE-Bond treated group displayed higher occlusion effects even after 4 weeks of treatment than did the other experimental groups. Therefore, it is the authors' belief that fluoride varnish and SE-Bond are effective for treating dentinal hyperesthesia.

The Effect of Mitomycin-c, Vinblastine, and Cisplatin(MVP) Combined Chemotherapy in Non-Small Cell Lung Cancer (진행된 비소세포성 폐암에 대한 MVP 복합화학요법의 효과)

  • Kim, Young-Woo;Park, Neung-Hwa;Ji, Sang-Keun;Choi, Hyun-Muck;Lee, Sin-Hwa;Lee, Keum-Hee;Jang, Tae-Won;Jung, Maan-Hong
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.1
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    • pp.76-83
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    • 1995
  • Background: Despite advances in chemotherapy, the treatment of inoperable non-small cell carcinoma of the lung remains poor. According to the recent reports, the response rates of mitomycin, vinblastine, and cisplatin(MVP) chemotherapy are higher than those of other cisplatin based polychemotherapy and MVP chemotherapy can be used as neoadjuvant chemotherapeutic regimen. But the overall response rates of MVP chemotherapy range from 17 to 53 percent, so we studied the effect of MVP chemotherapy in advanced non-small cell lung cancer. Method: We treated forty patients with stage III or IV non-small cell lung cancer with two courses of MVP chemotherapy($8mg/m^2$ of mitomycin on day 1, $6mg/m^2$ of vinblastine on day 2 & day 14, and $100mg/m^2$ of cisplastin on day 1) at 4 weeks interval. Then all patients were evaluated the response of chemotherapy 4 weeks later, and received further chemotherapy, palliative radiotherapy or supportive therapy according to the patient's condition. We also determined the median survival time and prognostic factors. Results: 1) Nine patients(23%) had a partial reponse, 23 patients(57%) had a stable disease, and disease progressed in 8 patients(20%). There were no patients with complete response. 2) The overall median survival time was 36 weeks(range, 9 to 119+ weeks). The median survival time of responder(partial response) and non-responder(stable and progressed) groups were 60 weeks(range, 36 to 82+ weeks) and 31 weeks(range, 9 to 119+ weeks) respectively(p=0.03). 3) The median survival time of the female group was 71 weeks and significantly prolonged in comparision with 35 weeks of the male group(p=0.01). But, the other prognostic factors didn't affect the survival time and response rate. 4) The median survival times of chemotherapy group and chemotherapy with palliative radiotherapy group were not significantly different. Conclusion: MVP combined chemotherapy is unsatisfactory in improving survival in advanced non-small cell lung cancer. Therefore, further studies are needed to find more active new agents and to estabilish the efficacy of the combined treatment with radiotherapy and/or surgery.

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Strain Improvement through Protoplast Formation and Mutation of Inonotus obliquus Mycelia for Enhanced Production of Innerpolysaccharides (IPS) in Suspended Mycelial Cultures (Inonotus obliquus 의 균사체 액상배양에서 원형질체 형성과 돌연변이를 통한 단백다당체 고생산성 균주 개발)

  • Hong, Hyeong-Pyo;Jeong, Yong-Seob;Chun, Gie-Taek
    • KSBB Journal
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    • v.25 no.2
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    • pp.155-166
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    • 2010
  • Studies on the production of cell-wall bound innerpolysaccharides (IPS) (soluble ${\beta}$-D-glucan) have been performed by use of suspended myelial cultures of Inonotus obliquus. This product has promising potentials as an effective antidiabetic as well as an immunostimulating agents. As a first step to enhanced production of IPS, Intensive strain improvement programs were carried out by obtaining a large amounts of protoplasts for the isolation of single cell colonies. Rapid and large screening of high-yielding producers was possible because about fivefold higher amount of protoplasts ($2.3{\times}10^6$ protoplasts/mL) could be recovered with relatively high regeneration rates of $10^{-2}{\sim}10^{-3}$ by applying a modified filtration method, as compared to the previously used trapping method. A basic protocol necessary for UV-mutation of the protoplasts was also developed, resulting in several overproducing variants with good fermentation properties. Since the amount of IPS extracted from the mycelial cell walls of I. obliquus turned out to be almost constant per g DCW, increase in cell mass was considered the most important factor for the enhancement in IPS production. Therefore, attempts were made to screen mutant cells showing rapid mycelial growth rate in the final suspended cultures. Notably, the mutant strains showing an active cellgrowth in the preceding solid growth cultures were observed to produce higher amount of IPS in the suspended fermentations as well. A striking mutant, OBLQ756-15-5 strain, obtained from the survivors of a harsh UV-treated condition (97% death rate) was found to stably produce as high cell mass as 22 g DCW/L in the final fermentations. Currently, this strain is being tested for development of a scaled-up fermentation process for mass production of IPS.

Prevalence and Clinical Outcome of Penicillin-resistant Pneumococcal Pneumonia (폐렴구균에 의한 지역사회 획득 폐렴에서 페니실린 내성률과 내성에 따른 임상경과에 관한 연구)

  • Hong, Ji Hyun;Lee, Hyung Seok;Jung, Seung Hyun;Kim, Gyu Won;Eom, Kwang-Seok;Lee, Jae Myung;Jang, Seung Hun;Kim, Dong Gyu;Hyoen, In Gyou;Lee, Myoung Koo;Park, Yong Bum;Jung, Ki-Suck;Lee, Young Kyoung
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.3
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    • pp.295-303
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    • 2003
  • Backgroung : The incidence of penicillin-resistant streptococcus pneumoniae(PRSP) accounts for almost 70% of all pneumococcal pneumonia cases in Korea. It is still unclear as to whether the efficacy of penicillin or equally active beta-lactam agents is compromised in PRSP pneumonia. This study investigated the prevalence of PRSP in community-acquired pneumonia and its clinical course. Methods : A total of 42 patients with community-acquired pneumococcal pneumonia were evaluated from July 1999 to May 2001. The cultured strains of Streptococcus pneumoniae were divided into susceptible, intermediately resistant, and resistant strains by an E-test, and the effect of the clinical course was investigated. Results : From a total of 42 patients, 22 (52.4%) patients had an intermediate resistance (MIC $0.1-1{\mu}g/m{\ell}$) and six (14.3%) showed a high resistance ($MIC{\geq}2.0{\mu}g/m{\ell}$) with current penicillin susceptibility categories. However, according to the classification of the DRSPTWG (Drug Resistant Streptococcus pneumoniae Therapeutic Working Group), there were 11 cases (26.2%) of intermediate resistance and no case of high resistance. Under empirical antimicrobial treatment, there was no difference in the clinical outcome between the penicillin susceptible and resistant group. Conclusion : The clinical outcome of PRSP pneumonia with empirical therapy was acceptable. These results suggest that the current MIC breakpoint for penicillin resistance in Streptococcus pneumoniae has been set at a very low level and penicillin resistance according to the NCCLS classification does not significantly influence the outcome of the empirical treatment for pneumococcal pneumonia.

The Preventive Measures On Terrorism Against Overseas Korean Businessmen(A view of recent ethnic minority separation movement) (해외근무(海外覲務) 기업체(企業體)에 대(對)한 테러 방지책(防止策) - 최근(最近) 소수민족분리주의운동지역(小數民族分離主義運動地域)을 중심(中心)으로 -)

  • Choi, Yoon-Soo
    • Korean Security Journal
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    • no.1
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    • pp.351-370
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    • 1997
  • This study concerns possible measures to prevent separatists' terrorist acts against overseas Korean businessmen. Of late, many Korean enterprises are helping a number of foreign countries develop their economy, by building factories and manning regional offices in those countries. But recent development of terrorism especially against Korean businessmen is alarming. This report discusses the need for Korean enterprises heading overseas to prepare themselves with awareness of terrorism and possible protective measures against it, besides their routine pursuance of profits; and for the government and prospective enterprises to refrain from investing in those countries having active separatist movements. If an investment has become inevitable, a careful survey of the region in conflict should be conducted and self-protective measures should be put in place through security information exchange, emergency coordination and training of personnel, etc. This study will first review the past terrorist incidents involving employees of overseas Korean enterprises, and then will focuss on seeking effective measures on the basis of the reported incidents. In carrying out the study, related literature from both home and abroad have been used along with the preliminary materials reported and known on the Internet from recent incidents. 1. The separatist movements of minority groups Lately, minority separatist groups are increasingly resorting to terrorism to draw international attention with the political aim of gaining extended self rule or independence. 2. The state of terrorism against overseas Korean enterprises and Koreans Korean enterprises are now operating businesses, and having their own personnel stationed, in 85 countries including those in South East Asia and Middle East regions. In Sri Lanka, where a Korean enterprise recently became a target of terrorist bombing, there are 75 business firms from Korea and some 700 Korean employees are stationed as of August 1996. A total of 19 different terrorist incidents have taken place against Koreans abroad since 1990. 3. Terrorism preventive measures Terrorism preventive measures are discussed in two ways: measures by the government and by the enterprises. ${\blacktriangleleft}$ Measures by the government - Possible measures at governmental level can include collection and dissemination of terrorist activity information. Emphasis should be given to the information on North Korean activities in particular. ${\blacktriangleleft}$ Measures by individual enterprises - Organizational security plan must be established by individual enterprises and there should also be an increase of security budget. A reason for reluctant effort toward positive security plan is the perception that the security budget is not immediately linked to an increment of profit gain. Ensuring safety for overseas personnel is a fundamental obligation of an enterprise. Consultation and information exchange on security plan, and an emergency support system at a threat to security must be sought after and implemented. 4. Conclusion Today's terrorism varies widely depending on reasons and causes, and its means has become increasingly informationalized and scientific as well while its method is becoming more clandestine and violent. Terrorist organizations are increasingly aiming at enterprises for acquisition of budgets needed for their activities. Korean enterprises have extended their business realm to foreign countries since 1970, exposing themselves to terrorism. Enterprises and their employees, therefore, should establish their own security measures on the one hand while the government must provide general measures, on the other, for the protection of the life and property of Korean residents abroad from terrorist attacks. In this regard, set-up of a counter terrorist organization that coordinates the efforts of government authorities in various levels in planning and executing counter terrorist measures is desired. Since 1965, when the hostile North Korea began to step up its terrorist activities against South Koreans, there have been 7 different occasions of assassination attempt on South Korean presidents and some 500 cases of various kidnappings and attempted kidnappings. North Korea, nervous over the continued economic growth and social stabilization of South Korea, is now concentrating its efforts in the destruction and deterioration of the national power of South Korea for its earlier realization of reunification by force. The possibility of North Korean terrorism can be divided into external terrorist acts and internal terrorist acts depending on the nationality of the terrorists it uses. The external terrorist acts include those committed directly by North Korean agents in South Korea and abroad and those committed by dissident Koreans, hired Korean residents, or international professionals or independent international terrorists bought or instigated by North Korea. To protect the life and property of Korean enterprises and their employees abroad from the threat of terrorism, the government's administrative support and the organizational efforts of enterprises should necessarily be directed toward the planning of proper security measures and training of employees. Also, proper actions should be taken against possible terrorist acts toward Korean business employees abroad as long as there are ongoing hostilities from minority groups against their governments.

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In Search of "Excess Competition" (과당경쟁(過當競爭)과 정부규제(政府規制))

  • Nam, II-chong;Kim, Jong-seok
    • KDI Journal of Economic Policy
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    • v.13 no.4
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    • pp.31-57
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    • 1991
  • Korean firms of all sizes, from virtually every industry, have used and are using the term "excessive competition" to describe the state of their industry and to call for government interventions. Moreover, the Korean government has frequently responded to such calls in various ways favorable to the firms, such as controlling entry, curbing capacity investments, or allowing collusion. Despite such interventions' impact on the overall efficiency on the Korean economy as well as on the wealth distribution among diverse groups of economic agents, the term "excessive competition", the basis for the interventions, has so far escaped rigorous scrutiny. The objective of this paper is to clarify the notion of "excessive competition" and "over-investment" which usually accompanies "excessive competition", and to examine the circumstances under which they might occur. We first survey the cases where the terms are most widely used and proceed to examine those cases to determine if competition is indeed excessive, and if so, what causes "excessive competition". Our main concern deals with the case in which the firms must make investment decisions that involve large sunk costs while facing uncertain demand. In order to analyze this case, we developed a two period model of capacity precommitment and the ensuing competition. In the first period, oligopolistic firms make capacity investments that are irreversible. Demand is uncertain in period 1 and only the distribution is known. Thus, firms must make investment decisions under uncertainty. In the second period, demand is realized, and the firms compete with quantity under realized demand and capacity constraints. In the above setting, we find that there is "no over-investment," en ante, and there is "no excessive competition," ex post. As measured by the information available in period 1, expected return from investment of a firm is non-negative, overall industry capacity does not exceed the socially optimal level, and competition in the second period yields an outcome that gives each operating firm a non-negative second period profit. Thus, neither "excessive competition" nor "over-investment" is possible. This result will generally hold true if there is no externality and if the industry is not a natural monopoly. We also extend this result by examining a model in which the government is an active participant in the game with a well defined preference. Analysis of this model shows that over-investment arises if the government cannot credibly precommit itself to non-intervention when ex post idle capacity occurs, due to socio-political reasons. Firms invest in capacities that exceed socially optimal levels in this case because they correctly expect that the government will find it optimal for itself to intervene once over-investment and ensuing financial problems for the firms occur. Such planned over-investment and ensuing government intervention are the generic problems under the current system. These problems are expected to be repeated in many industries in years to come, causing a significant loss of welfare in the long run. As a remedy to this problem, we recommend a non-intervention policy by the government which creates and utilizes uncertainty. Based upon an argument which is essentially the same as that of Kreps and Wilson in the context of a chain-store game, we show that maintaining a consistent non-intervention policy will deter a planned over-investment by firms in the long run. We believe that the results obtained in this paper has a direct bearing on the public policies relating to many industries including the petrochemical industry that is currently in the center of heated debates.

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