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International Law on the Flight over the High Seas (공해의 상공비행에 관한 국제법)

  • Kim, Han-Taek
    • The Korean Journal of Air & Space Law and Policy
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    • v.26 no.1
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    • pp.3-30
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    • 2011
  • According to the Article 86 of the United Nations on the Law of the Sea(UNCLOS) the provisions of high seas apply to all parts of the sea that are not included in the exclusive economic zone, in the territorial sea or in the internal waters of a State, or in the archipelagic waters of an archipelagic State. Article 87 also stipulates the freedom of the high seas. International laws on the flight over the high seas are found as follows; Firstly, as far as the nationality of the aircraft is concerned, its legal status is quite different from the ship where the flags of convenience can be applied practically. There is no flags of convenience of the aircraft. Secondly, according to the Article 95 of UNCLOS warships on the high seas have complete immunity from the jurisdiction of any State other than the flag State. We can suppose that the military(or state) aircraft over the high seas have also complete immunity from the jurisdiction of any State other than the flag State. Thirdly, according to the Article 101 of UNCLOS piracy consists of any act of voluntary participation in the operation of a ship or of an aircraft with knowledge of facts making it a pirate ship or aircraft. We can conclude that piracy can de done by a pirate aircraft as well as a pirate ship. Fourthly, according to the Article 111 (5) of UNCLOS the right of hot pursuit may be exercised only by warships or military aircraft, or other ships or aircraft clearly marked and identifiable as being on government service and authorized to that effect. We can conclude that the right of hot pursuit may be exercised only military aircraft, or aircraft clearly marked and identifiable as being on government service and authorized to that effect. Fifthly, according to the Article 110 of UNCLOS a warship which encounters on the high seas a foreign ship, is not justified in boarding it unless there is reasonable ground for suspecting that: (a) the ship is engaged in piracy, (b) the ship is engaged in the slave trade, (c) the ship is engaged in an authorized broadcasting and the flag State of the warship has jurisdiction under article 109, (d) the ship is without nationality, or (e) though flying a foreign flag or refusing to show its flag, the ship is, in reality, of the same nationality as the warship. These provisions apply mutatis mutandis to military aircraft. Sixthly, according to the Article 1 (5)(dumping), 212(pollution from or through the atmosphere), 222(enforcement with respect to pollution from or through the atmosphere) of UNCLOS aircraft as well as ship is very much related to marine pollution. Seventhly, as far as the crime on board aircraft over the high seas is concerned 1963 Convention on the Offences and Certain Other Acts Committed on Board Aircraft(Tokyo Convention) will be applied, and as for the hijacking over the high seas 1970 Convention for the Suppression of Unlawful Seizure of Aircraft(Hague Convention) and as for the sabotage over the high seas 1971 Convention for the Suppression of Unlawful Acts Against the Safety of Civil Aviation(Montreal Convention) will be applied respectively. These three conventions recognize the flag state jurisdiction over the crimes on board aircraft over the high seas. Eightly, as far as reconnaissance by foreign aircraft in the high seas toward the coastal States is concerned it is not illegal in terms of international law because its act is done in the high seas. Ninthly as for Air Defence Identification Zone(ADIZ) there are no articles dealing with it in the 1944 Chicago Convention. The legal status of the foreign aircraft over this sea zone might be restricted to the regulations of the coastal states whether this zone is legitimate or illegal. Lastly, the Arctic Sea is the frozen ocean. So the flight over that ocean is the same over the high seas. Because of the climate change the Arctic Sea is getting melted. If the coastal states of the Arctic Sea will proclaim the Exclusive Economic Zone(EEZ) as the ocean is getting melted, the freedom of flight over that ocean will also be restricted to the regulations of the coastal states.

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A Legal Study on liability for damages cause of the air carrier : With an emphasis upon liability of passenger (항공운송인의 손해배상책임 원인에 관한 법적 고찰 - 여객 손해배상책임을 중심으로 -)

  • So, Jae-Seon;Lee, Chang-Kyu
    • The Korean Journal of Air & Space Law and Policy
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    • v.28 no.2
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    • pp.3-35
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    • 2013
  • Air transport today is a means of transport that is optimized for exchanges between nations. Around the world, has experienced an increase in operating and the number of airline route expansion that has entered into the international aviation agreements in order to take advantage of the air transport efficient, but the possibility of the occurrence of air transport accidents increased. When compared to the accident of other means of transport, development of air transport accidents, not high, but it leads to catastrophe aviation accident occurs. Air Transport accident many international transportation accident than domestic transportation accident, in the event of an accident, the analysis of the legal responsibility of the shipper or the like is necessary or passenger air carrier. Judgment of the legal order of discipline of air transport accident is a classification of the type of air transport agreement. Depending on the object, air transport agreements are classified into the contract of carriage of aviation of the air passenger transportation contract. For casualties occurs, air passenger transportation accident is a need more discussion of legal discipline for this particular. Korean Commercial Code, it is possible to reflect in accordance with the actual situation of South Korea the contents of the treaty, which is utilized worldwide in international air transport, even on the system, to control land, sea, air transport and welcoming to international standards. However, Korean Commercial Code, the problem of the Montreal Convention has occurred as it is primarily reflecting the Montreal Convention. As a cause of liability for damages, under the Commercial Code of Korea and the contents of the treaty precedent is reflected, the concept of accident is necessary definition of the exact concept for damages of passengers in particular. Cause of personal injury or death of passengers, in the event of an accident to the "working for the elevation" or "aircraft" on, the Montreal Convention is the mother method of Korea Commercial Code, liability for damages of air carrier defines. The Montreal Convention such, continue to be a matter of debate so far in connection with the scope of "working for the lifting of" the concepts defined in the same way from Warsaw Convention "accident". In addition, it is discussed and put to see if you can be included mental damage passenger suffered in air transport in the "personal injury" in the damage of the passenger is in the range of damages. If the operation of aircraft, injury accident, in certain circumstances, compensation for mental damage is possible, in the same way as serious injury, mental damage caused by aviation accidents not be able to live a normal life for the victim it is damage to make. So it is necessary to interpret and what is included in the injury to the body in Korea Commercial Code and related conventions, non-economic damage of passengers, clearly demonstrated from the point of view of prevention of abuse of litigation and reasonable protection of air carrier it must compensate only psychological damage that can be. Since the compensation of delay damages, Warsaw Convention, the Montreal Convention, Korea Commercial Code, there are provisions of the liability of the air carrier due to the delayed arrival of passenger and baggage, but you do not have a reference to delayed arrival, the concept of delay arrangement is necessary. The strict interpretation of the concept of delayed arrival, because it may interfere with safe operation of the air carrier, within the time agreed to the airport of arrival that is described in the aviation contract of carriage of passenger baggage, or, these agreements I think the absence is to be defined as when it is possible to consider this situation, requests the carrier in good faith is not Indian or arrive within a reasonable time is correct. The loss of passenger, according to the international passenger Conditions of Carriage of Korean Air, in addition to the cases prescribed by law and other treaties, loss of airline contracts, resulting in passengers from a service that Korean Air and air transport in question do damage was is, that the fact that Korean Air does not bear the responsibility as a general rule, that was caused by the negligence or intentional negligence of Korean Air is proof, negligence of passengers of the damage has not been interposed bear responsibility only when it is found. It is a clause in the case of damage that is not mandated by law or treaty, and responsible only if the negligence of the airline side has been demonstrated, but of the term negligence "for" intentional or negligent "Korean Air's Terms" I considered judgment of compatibility is required, and that gross negligence is appropriate. The "Korean Air international passenger Conditions of Carriage", airlines about the damage such as electronic equipment that is included in the checked baggage of passengers does not bear the responsibility, but the loss of baggage, international to arrive or depart the U.S. it is not the case of transportation. Therefore, it is intended to discriminate unfairly passengers of international flights arriving or departure to another country passengers of international flights arriving or departure, the United States, airlines will bear the responsibility for the goods in the same way as the contents of the treaty it should be revised in the direction.

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The Liability for Space Activity of Launching State of Space Object and Improvement of Korea's Space Policy (우주물체 발사국의 우주활동에 대한 책임과 우리나라 우주정책의 개선방향)

  • Lee, Kang-Bin
    • The Korean Journal of Air & Space Law and Policy
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    • v.28 no.2
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    • pp.295-347
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    • 2013
  • Korea launched the science satellite by the first launch vehicle Naro-ho(KSLV-1) at the Naro Space Center located at Oinarodo, Cohenggun Jellanamdo in August, 2009 and October, 2010. However, the first and second launch failed. At last, on January 30, 2013 the third launch of the launch vehicle Naro-ho has successfully launched and the Naro science satellite penetrated into the space orbit. Owing to the succeed of the launch of Naro-ho, Korea joined the space club by the eleventh turn following the United States, Russia, Japan and China. The United Nations adopted the Outer Space Treaty of 1967, the Rescue Agreement of 1968, the Liability Convention of 1972, the Regislation Convention of 1976, and Moon Agreement of 1979. Korea ratified the above space-related treaties except the Moon Agreement. Such space-related treaties regulate the international liability for the space activity by the launching state of the space object. Especially the Outer Space Treaty regulates the principle concerning the state's liability for the space activity. Each State Party to the Treaty that launches or procures the launching of an object into outer space is internationally liable for damage to another State Party or to its natural or judicial persons by such object or its component parts on the earth, in air space or in outer space. Under the Liability Convention, a launching state shall be absolutely liable to pay compensation for damage caused by its space object on the surface of the earth or to aircraft in flight. The major nations of the world made national legislations to observe the above space-related treaties, and to promote the space development, and to regulate the space activity. In Korea, the United States, Russia and Japan, the national space-related legislation regulates the government's liability of the launching state of the space object. The national space-related legislations of the major nations are as follows : the Outer Space Development Promotion Act and Outer Space Damage Compensation Act of Korea, the National Aeronautic and Space Act and Commercial Space Launch Act of the United States, the Law on Space Activity of Russia, and the Law concerning Japan Aerospace Exploration Agency and Space Basic Act of Japan. In order to implement the government's liability of the launching state of space object under space-related treaties and national legislations, and to establish the standing as a strong space nation, Korea shall improve the space-related policy, laws and system as follows : Firstly, the legal system relating to the space development and the space activity shall be maintained. For this matter, the legal arrangement and maintenance shall be made to implement the government's policy and regulation relating to the space development and space activity. Also the legal system shall be maintained in accordance with the elements for consideration when enacting the national legislation relevant to the peaceful exploration and use of outer space adopted by UN COPUOS. Secondly, the liability system for the space damage shall be improved. For this matter, the articles relating to the liability for the damage and the right of claiming compensation for the expense already paid for the damage in case of the joint launch and consigned launch shall be regulated newly. Thirdly, the preservation policy for the space environment shall be established. For this matter, the consideration and preservation policy of the environment in the space development and use shall be established. Also the rule to mitigate the space debris shall be adopted. Fourthly, the international cooperation relating to the space activity shall be promoted. For this matter, the international cooperation obligation of the nation in the exploration and use of outer space shall be observed. Also through the international space-related cooperation, Korea shall secure the capacity of the space development and enter into the space advanced nation.

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A Study on the Meaning of Outer Space Treaty in International Law (우주조약의 국제법적 의미에 관한 연구)

  • Kim, Han-Taek
    • The Korean Journal of Air & Space Law and Policy
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    • v.28 no.2
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    • pp.223-258
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    • 2013
  • 1967 Outer Space Treaty(Treaty on Principles Governing the Activities of States in the Exploration and Use of Outer Space, including the Moon and Other Celestial Bodies; OST) is a treaty that forms the basis of international space law. OST is based on the 1963 Declaration of Legal Principles Governing the Activities of States in the Exploration and Use of Outer Space announced by UNGA resolution. As of May 2013, 102 countries are states parties to OST, while another 27 have signed the treaty but have not completed ratification. OST explicitly claimed that the Moon and Other Celestial Bodies are the province of all mankind. Art. II of OST states that "outer space, including the Moon and other celestial bodies, is not subject to national appropriation by claim of sovereignty, by means of use or occupation, or by any other means", thereby establishing res extra commercium in outer space like high seas. However 1979 Moon Agreement stipulates that "the moon and its natural resources are the Common Heritage of Mankind(CHM)." Because of the number of the parties to the Moon Agreement(13 parties) it does not affect OST. OST also established its specific treaties as a complementary means such as 1968 Rescue Agreement, 1972 Liability Convention, 1975 Registration Convention. OST bars states party to the treaty from placing nuclear weapons or any other weapons of mass destruction in orbit of Earth, installing them on the Moon or any other celestial body, or to otherwise station them in outer space. It exclusively limits the use of the Moon and other celestial bodies to peaceful purposes and expressly prohibits their use for testing weapons of any kind, conducting military maneuvers, or establishing military bases, installations, and fortifications. However OST does not prohibit the placement of conventional weapons in orbit. China and Russia submitted Draft Treaty on the Prevention of the Placement of Weapon in Outer Space and of the Threat or Use of Force against Outer Space Objects(PPWT) on the Conference on Disarmament in 2008. USA disregarded PPWT on the ground that there are no arms race in outer space. OST does not have some articles in relation to current problems such as space debris, mechanisms of the settlement of dispute arising from state activities in outer space in specific way. COPUOS established "UN Space Debris Mitigation Guidelines" based on "IADC Space Debris Mitigation Guidelines" and ILA proposed "International Instrument on the Protection of the Environment from Damage Caused by Space Debris" for space debris problems and Permanent Court of Arbitration(PCA) established "Optional Rules for Arbitration of Disputes Relating to Outer Space Activities" and ILA proposed "1998 Taipei Draft Convention on the Settlement of Space Law Dispute" for the settlement of dispute problems. Although OST has shortcomings in some articles, it is very meaningful in international law in considering the establishment of basic principles governing the activities of States in the exploration and use of outer space, including the Moon and Other Celestial Bodies. OST established the principles governing the activities of states in the exploration and use of outer space as customary law and jus cogens in international law as follows; the exploration and use of outer space shall be carried out for the benefit and in the interests of all countries and shall be the province of all mankind; outer space shall be free for exploration and use by all States; outer space is not subject to national appropriation by claim of sovereignty, by means of use or occupation, or by any other means. The principles of global public interest in outer space imposes international obligations erga omnes applicable to all States. This principles find significant support in legal norms dealing with following points: space activities as the "province of all mankind"; obligation to cooperate; astronauts as envoys of mankind; avoidance of harmful contamination; space activities by States, private entities and intergovernmental organisations; absolute liability for damage cauesd by certain space objects; prohibition of weapons in space and militarization of the celestial bodies; duty of openness and transparency; universal application of the international space regime.

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Internet Addiction in Adolescents and its Relation to Sleep and Depression (청소년의 인터넷 중독 : 수면, 우울과의 관련성)

  • Song, Ho-Kwang;Jeong, Mi-Hyang;Sung, Da-Jung;Jung, Jung-Kyung;Choi, Jin-Sook;Jang, Yong-Lee;Lee, Jin-Seong
    • Sleep Medicine and Psychophysiology
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    • v.17 no.2
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    • pp.100-108
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    • 2010
  • Objectives: "Internet-addiction" came into common use not only in clinical setting but also in everyday life. But, pathophysiology and diagnostic criteria of the internet addiction remain unknown. Because adolescents are in developing period, they might be vulnerable to the internet addiction, depression and sleep-related problem. The objectives of this study were to investigate the characteristics of internet addiction and its association with sleep pattern and depression in Korean adolescence. Methods: Subjects were 799 middle and high school students in Seoul, Korea. We administered a self-reported questionnaire including socio-demographic data, Korean versions of Young's Internet Addiction Scale (YIAS), Pittsburgh Sleep Quality Index (PS-QI), the Center for Epidemiologic Studies for Depression Scale (CES-D) and questions about internet using patterns. Data of 696 subjects were included in analysis. Chi-square tests were used to analyze proportional differences, and ANOVA with post-hoc tests were used to analyze differences among groups. Partial correlation analyses were performed to analyze the correlation of internet addiction with other variables (two-tailed, p<0.05). Results: Of the 696 participants (grade 2 of middle school; M2 135 vs. grade 1 of high school; H1 238 vs. grade 2 of high school; H2 323), 2.0% (n=14) were internet-addicted (IA), 27.7% (n=193) were over-using (OU) and 70.3% (n=489) were not-addicted (NA). The mean scores of YIAS, PSQI and CES-D scores were 35.24${\pm}$12.78, 5.53${\pm}$3.04 and 16.72${\pm}$8.69, respectively. In higher grade students, average total sleep time was shorter (M2 426.20${\pm}$67.68 min. vs. H1 380.47${\pm}$62.57 min. vs. H2 354.67${\pm}$73.37 min., F=51.909, p<0.001), and PSQI (4.69${\pm}$3.14 vs. 5.42${\pm}$3.15 vs. 5.97${\pm}$2.83, F=8.871, p<0.001) CES-D (13.53${\pm}$8.37 vs. 16.96${\pm}$8.24 vs. 17.87${\pm}$8.84, F=12.373, p<0.001) scores were higher than those of lower grade students. Comparing variables among IA, OU and NA groups, computer using time not for study (96.36${\pm}$63.31 min. vs. 134.92${\pm}$86.79 min. vs. 213.57${\pm}$136.87 min., F=34.287, p<0.001) and portable device using time not for study (84.22${\pm}$79.11 min. vs. 96.97${\pm}$91.89 min. vs. 152.31${\pm}$93.64 min., F= 5.400, p=0.005) were different among groups. PSQI (5.26${\pm}$2.97 vs. 6.08${\pm}$2.97 vs. 7.50${\pm}$4.41, F=8.218, p<0.001) and CES-D scores (15.40${\pm}$8.08 vs. 19.05${\pm}$8.42 vs. 30.43${\pm}$13.69, F=32.692, p<0.001) were also different among groups. YIAS score were correlated with computer using time not for study (r=0.356, p<0.001) and portable device using time not for study (r= 0.136, p<0.001). PSQI score (r=0.237, p<0.001) and CES-D score (r=0.332, p<0.001). YIAS score and PSQI score (r=0.131, p= 0.001), YIAS and CES-D score (r=0.265, p<0.001), PSQI score and CES-D score (r=0.357, p<0.001) were correlated each other. Conclusion: These results suggested that adolescents' internet-addiction was correlated with not only computer and portable device using time not for study but also depression and sleep-related problems. We should pay attention to depression and sleep-related problems, when evaluating internet-addiction in adolescents.

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The study for the roles of intratracheally administered histamine in the neutrophil-mediated acute lung injury in rats: (호중구를 매개하는 백서의 급성 폐손상의 병리가전에 있어 기도내로 투여한 히스타민의 역활에 관하여)

  • Koh, Youn-Suck;Hybertson, Brooks M.;Jepson, Eric K.;Kim, Mi-Jung;Lee, In-Chul;Lim, Chae-Man;Lee, Sang-Do;Kim, Dong-Soon;Kim, Won-Dong;Repine, John E.
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.3
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    • pp.308-322
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    • 1996
  • Background : Neutrophils are considered to play critical roles in the development of acute respiratory distress syndrome. Histamine, which is distributed abundantly in lung tissue, increases the rolling of neutrophills via increase of P-selectin expression on the surface of endothelial cells and is known to have some interrelationships with IL-1, IL-8 and TNF-$\alpha$. We studied to investigate the effect of the histamine on the acute lung injury of the rats induced by intratracheal insufflation of TNF-$\alpha$ which has less potency to cause lung injury compared to IL-1 in rats. Methods : We intratracheally instilled saline or TNF(R&D, 500ng), IL-1(R&D, 50ng)or histamine of varius dose(1.1, 11 and $55\;{\mu}g/kg$) with and without TNF separately in Sprague-Dawley rats weighing 270-370 grams. We also intratracheally treated IL-1(50ng) along with histamine($55\;{\mu}g/kg$). In cases, there were synergistic effects induced by histamine on the parameters of TNF-induced acute lung injury, antihistamines(Sigma, mepyramine as a $H_1$ receptor blockade and ranitidine as a $H_2$ receptor blockade, 10 mg/kg in each)were co-administered intravenously to the rats treated TNF along with histamine($1.1\;{\mu}g/kg$) intratraeheally. Then after 5 h we measured lung lavage neutrophil numbers, lavage cytokine-induced neutrophil chemoattractants(CINC), lung myeloperoxidase activity(MPO) and lung leak. We also intratracheally insufflated TNF with/without histamine($11\;{\mu}g/kg$), then after 24 h measured lung leak in rats. Statistical analyses were done by Kruskal-Wallis nonparametric ANOVA test with Dunn's multiple comparison test or by Mann-Whitney U test. Results : We found that rats given TNF, histamine alone(11 and $55\;{\mu}g/kg$), and TNF with histamine(l.1, 11, and $55\;{\mu}g/kg$) intratracheally had increased (p<0.05) lung MPO activity compared with saline-treated control rats. TNF with histamine $11\;{\mu}g/kg$ had increased MPO activity (P=0.0251) compared with TNF-treated rats. TNF and TNF with histamine(1.1, 11, and $55\;{\mu}g/kg$) intratracheally had all increased (p<0.05) lung leak, lavage neutophil numbers and lavage CINC activities compared with saline. TNF with histamine $1.1\;{\mu}g/kg$ had increased (p=0.0367) lavage neutrophil numbers compared with TNF treated rats. But there were no additive effect of histamine with TNF compared with TNF alone in acute lung leak on 5 h and 24 h in rats. Treatment of rats with the $H_1$ and $H_2$ antagonists resulted in inhibitions of lavage neutrophil accumulations and lavage CINC activity elevations elicited by co-treated histamine in TNF-induced acute lung injury intratracheally in rats. We also found that rats given IL-1 along with histamine intratracheally did not have increase in lung leak compared with IL-1 treated rats. Conclusion : Histamine administered intratracheally did not have synergistic effects on TNF-induced acute lung leak inspite of additive effects on increase in MPO activity and lavage neutrophil numbers in rats. These observations suggest that instilling histamine intratracheally would not play synergistic roles in neutrophil-mediated acute lung injury in rats.

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Lipopolysaccharide-induced Synthesis of IL-1beta, IL-6, TNF-alpha and TGF-beta by Peripheral Blood Mononuclear Cells (내독소에 의한 말초혈액 단핵구의 IL-1beta, IL-6, TNF-alpha와 TGF-beta 생성에 관한 연구)

  • Jung, Sung-Hwan;Park, Choon-Sik;Kim, Mi-Ho;Kim, Eun-Young;Chang, Hun-Soo;Ki, Shin-Young;Uh, Soo-Taek;Moon, Seung-Hyuk;Kim, Yang-Hoon;Lee, Hi-Bal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.846-860
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    • 1998
  • Background: Endotoxin (LPS : lipopolysaccharide), a potent activator of immune system, can induce acute and chronic inflammation through the production of cytokines by a variety of cells, such as monocytes, endothelial cells, lymphocytes, eosinophils, neutrophils and fibroblasts. LPS stimulate the mononucelar cells by two different pathway, the CD14 dependent and independent way, of which the former has been well documented, but not the latter. LPS binds to the LPS-binding protein (LBP), in serum, to make the LPS-LBP complex which interacts with CD14 molecules on the mononuclear cell surface in peripheral blood or is transported to the tissues. In case of high concentration of LPS, LPS can stimulate directly the macrophages without LBP. We investigated to detect the generation of proinflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-$\alpha$ and fibrogenic cytokine, TGF-$\beta$, by peripheral blood mononuclear cells (PBMC) after LPS stimulation under serum-free conditions, which lacks LBPs. Methods : PBMC were obtained by centrifugation on Ficoll Hypaque solution of peripheral venous bloods from healthy normal subjects, then stimulated in the presence of LPS (0.1 ${\mu}g/mL$ to 100 ${\mu}g/mL$ ). The activities of IL-1, IL-6, TNF, and TGF-$\beta$ were measured by bioassaies using cytokines - dependent proliferating or inhibiting cell lines. The cellular sources producing the cytokines was investigated by immunohistochemical stains and in situ hybridization. Results : PBMC started to produce IL-6, TNF-$\alpha$ and TGF-$\beta$ in 1 hr, 4 hrs and 8hrs, respectively, after LPS stimulation. The production of IL-6, TNF-$\alpha$ and TGF-$\beta$ continuously increased 96 hrs after stimulation of LPS. The amount of production was 19.8 ng/ml of IL-6 by $10^5$ PBMC, 4.1 ng/mL of TNF by $10^6$ PBMC and 34.4 pg/mL of TGF-$\beta$ by $2{\times}10^6$ PBMC. The immunoreactivity to IL-6, TNF-$\alpha$ and TGF-$\beta$ were detected on monocytes in LPS-stimulated PBMC. Some of lymphocytes showed positive immunoreactivity to TGF-$\beta$. Double immunohistochemical stain showed that IL-1$\beta$, IL-6, TNF-$\alpha$ expression was not associated with CD14 postivity on monocytes. IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$mRNA expression were same as observed in immunoreactivity for each cytokines. Conclusion: When monocytes are stimulated with LPS under serum-free conditions, IL-6 and TNF-$\alpha$ are secreted in early stage of inflammation. In contrast, the secretion of TGF-$\beta$ arise in the late stages and that is maintained after 96 hrs. The main cells releasing IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ are monocytes, but also lymphocytes can secret TGF-$\beta$.

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The Effects of Proinflammatory Cytokines and TGF-beta, on The Fibroblast Proliferation (Proinflammatory Cytokines과 TGF-beta가 섬유모세포의 증식에 미치는 영향)

  • Kim, Chul;Park, Choon-Sik;Kim, Mi-Ho;Chang, Hun-Soo;Chung, Il-Yup;Ki, Shin-Young;Uh, Soo-Taek;Moon, Seung-Hyuk;Kim, Yong-Hoon;Lee, Hi-Bal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.861-869
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    • 1998
  • Backgrounds: The injury of a tissue results in the infalmmation, and the imflammed tissue is replaced by the normal parenchymal cells during the process of repair. But, constitutional or repetitive damage of a tissue causes the deposition of collagen resulting in the loss of its function. These lesions are found in the lung of patients with idiopathic pulmonary fibrosis, complicated fibrosis after diffuse alveolar damage (DAD) and inorganic dust-induced lung fibrosis. The tissue from lungs of patients undergoing episodes of active and/or end-stage pulmonary fibrosis shows the accumulation of inflammatory cells, such as mononuclear cells, neutrophils, mast cells and eosinophils, and fibroblast hyperplasia. In this regard, it appears that the inflammation triggers fibroblast activation and proliferation with enhanced matrix synthesis, stimulated by inflammatory mediators such as interleukin-1 (IL-1) and/or tumor necrosis factor (TNF). It has been well known that TGF-$\beta$ enhance the proliferation of fibroblasts and the production of collagen and fibronectin, and inhibit the degradation of collagen. In this regard, It is likely that TGF-$\beta$ undergoes important roles in the pathogenesis of pulmonary fibrosis. Nevertheless, this single cytokine is not the sole regulator of the pulmonary fibrotic response. It is likely that the balance of many cytokines including TGF-$\beta$, IL-1, IL-6 and TNF-$\alpha$ regulates the pathogenesis of pulmonary fibrosis. In this study, we investigate the interaction of TGF-$\beta$, IL-1$\beta$, IL-6 and TNF-$\alpha$ and their effect on the proliferation of fibroblasts. Methods: We used a human fibroblast cell line, MRC-5 (ATCC). The culture of MRC-5 was confirmed by immunofluorecent staining. First, we determined the concentration of serum in cuture medium, in which the proliferation of MRC-5 is supressed but the survival of MRC-5 is retained. Second, we measured optical density after staining the cytokine-stimulated cells with 0.5% naphthol blue black in order to detect the effect of cytokines on the proliferation of MRC-5. Result: In the medium containing 0.5% fetal calf serum, the proliferation of MRC-5 increased by 50%, and it was maintained for 6 days. IL-1$\beta$, TNF-$\alpha$ and IL-6 induced the proliferation of MRC-5 by 45%, 160% and 120%, respectively. IL-1$\beta$ and TNF-$\alpha$ enhanced TGF-$\beta$-induced proliferation of MRC-5 by 64% and 159%, but IL-6 did not affect the TGF-$\beta$-induced proliferation. And lNF-$\alpha$-induced proliferation of MRC-5 was reduced by IL-1$\beta$ in 50%. TGF-$\beta$, TNF-$\alpha$ and both induced the proliferation of MRC-5 to 89%, 135% and 222%, respectively. Conclusions: TNF-$\alpha$, TGF-$\beta$ and IL-1$\beta$, in the order of the effectiveness, showed the induction of MRC-5 proliferation of MRC-5. TNF-$\alpha$ and IL-1$\beta$ enhance the TGF-$\beta$-induced proliferation of MRC-5, but IL-6 did not have any effect TNF-$\alpha$-induced proliferation of MRC-5 is diminished by IL-1, and TNF-$\alpha$ and TGF-$\beta$ showed a additive effect.

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

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

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The National Survey of Open Lung Biopsy and Thoracoscopic Lung Biopsy in Korea (개흉 및 흉강경항폐생검의 전국실태조사)

  • 대한결핵 및 호흡기학회 학술위원회
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.1
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    • pp.5-19
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    • 1998
  • Introduction: Direct histologic and bacteriologic examination of a representative specimen of lung tissue is the only certain method of providing an accurate diagnosis in various pulmonary diseases including diffuse pulmonary diseases. The purpose of national survey was to define the indication, incidence, effectiveness, safety and complication of open and thoracoscopic lung biopsy in korea. Methods: A multicenter registry of 37 university or general hospitals equipped more than 400 patient's bed were retrospectively collected and analyzed for 3 years from the January 1994 to December 1996 using the same registry protocol. Results: 1) There were 511 cases from the 37 hospitals during 3 years. The mean age was 50.2 years(${\pm}15.1$ years) and men was more prevalent than women(54.9% vs 45.9%). 2) The open lung biopsy was performed in 313 cases(62%) and thoracoscopic lung biopsy was performed in 192 cases(38%). The incidence of lung biopsy was more higher in diffuse lung disease(305 cases, 59.7%) than in localized lung disease(206 cases, 40.3%) 3) The duration after abnormalities was found in chest X-ray until lung biopsy was 82.4 days(open lung biopsy: 72.8 days, thoracoscopic lung biopsy: 99.4 days). The bronchoscopy was performed in 272 cases(53.2%), bronchoalveolar lavage was performed in 123 cases(24.1%) and percutaneous lung biopsy was performed in 72 cases(14.1%) before open or thoracoscopic lung biopsy. 4) There were 230 cases(45.0%) of interstitial lung disease, 133 cases(26.0%) of thoracic malignancies, 118 cases(23.1%) of infectious lung disease including tuberculosis and 30 cases (5.9 %) of other lung diseases including congenital anomalies. No significant differences were noted in diagnostic rate and disease characteristics between open lung biopsy and thoracoscopic lung biopsy. 5) The final diagnosis through an open or thoracoscopic lung biopsy was as same as the presumptive diagnosis before the biopsy in 302 cases(59.2%). The identical diagnostic rate was 66.5% in interstitial lung diseases, 58.7% in thoracic malignancies, 32.7% in lung infections, 55.1 % in pulmonary tuberculosis, 62.5% in other lung diseases including congenital anomalies. 6) One days after lung biopsy, $PaCO_2$ was increased from the prebiopsy level of $38.9{\pm}5.8mmHg$ to the $40.2{\pm}7.1mmHg$(P<0.05) and $PaO_2/FiO_2$ was decreased from the prebiopsy level of $380.3{\pm}109.3mmHg$ to the $339.2{\pm}138.2mmHg$(P=0.01). 7) There was a 10.1 % of complication after lung biopsy. The complication rate in open lung biopsy was much higher than in thoracoscopic lung biopsy(12.4% vs 5.8%, P<0.05). The incidence of complication was pneumothorax(23 cases, 4.6%), hemothorax(7 cases, 1.4%), death(6 cases, 1.2%) and others(15 cases, 2.9%). 8) The 5 cases of death due to lung biopsy were associated with open lung biopsy and one fatal case did not describe the method of lung biopsy. The underlying disease was 3 cases of thoracic malignancies(2 cases of bronchoalveolar cell cancer and one malignant mesothelioma), 2 cases of metastatic lung cancer, and one interstitial lung disease. The duration between open lung biopsy and death was $15.5{\pm}9.9$ days. 9) Despite the lung biopsy, 19 cases (3.7%) could not diagnosed. These findings were caused by biopsy was taken other than target lesion(5 cases), too small size to interpretate(3 cases), pathologic inability(11 cases). 10) The contribution of open or thoracoscopic lung biopsy to the final diagnosis was defininitely helpful(334 cases, 66.5%), moderately helpful(140 cases, 27.9%), not helpful or impossible to judge(28 cases, 5.6%). Overall, open or thoracoscopic lung biopsy were helpful to diagnose the lung lesion in 94.4 % of total cases. Conclusions: The open or thoracoscopic lung biopsy were relatively safe and reliable diagnostic method of lung lesion which could not diagnosed by other diagnostic approaches such as bronchoscopy. We recommend the thoracoscopic lung biopsy when the patients were in critical condition because the thoracoscopic biopsy was more safe and have equal diagnostic results compared with the open lung biopsy.

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