The Value of Interleukin-12 as an Activity Marker of Pulmonary Sarcoidosis (폐유육종증의 활동성 지표로서 IL-12의 효용성에 관한 연구)
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- Tuberculosis and Respiratory Diseases
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- v.46 no.2
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- pp.215-228
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- 1999
Background: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology often involving the lungs and intrathoracic lymph nodes. The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. But, the mechanisms causing the variable clinical outcomes or any single parameter to predict the prognosis was not known. In sarcoidosis, the number and the activity of CD4 + lymphocytes are significantly increased at the loci of disease and their oligoclonality suggests that the CD4 + lymphocytes hyperreactivity may be caused by persistent antigenic stimulus. Recently, it has been known that CD4+ lymphocytes can be subdivided into 2 distinct population(Th1 and Th2) defined by the spectrum of cytokines produced by these cells. Th1 cells promote cellular immunity associated with delayed type hypersensitivity reactions by generating IL-2 and IFN-
The rule of the Warsaw Convention of 1929 are well known and still being all over the world. The Warsaw Convention is undoubtedly the most widely accepted private international air law treaty with some 140 countries. In the international legal system for air transportation, the Warsaw Convention has played a major role for more than half century, and has been revised many times in consideration of the rapid developments of air high technology, changes of social and economic circumstances, need for the protection of passengers. Some amendments became effective, but others are still not effective. As a result, the whole international legal system for air transportation is at past so complicated and tangled. However, the 'Warsaw system' consists of the Warsaw Convention of 1929 the Guadalajara Convention of 1961, a supplementary convention, and the following six protocols: (1) the Hague Protocol of 1955, (2) the Guatemala Protocol of 1971, (3) the Montreal Additional Protocols, No.1, (4) the Montreal Additional Protocol No.2, (5) the Montreal Additional Protocol No.3, and (6) the Montreal Additional Protocol No.4. of 1975. As a fundamental principle of the air carrier's liability in the international convention and protocols, for instance in the Warsaw Convention and the Hague Protocol, the principle of limited liability and a presumed fault system has been adopted. Subsequently, the Montreal Inter-carrier Agreement of 1966, the Guatemala City Protocol, the Montreal Additional Protocol No.3, and the Montreal Additional Protocol No. 4 of 1975 maintained the limited liability, but substituted the presumed liability system by an absolute liability, that is, strict liability system. The Warsaw System, which sets relatively low compensation limits for victims of aircraft accidents and regulates the limited liability for death and injury of air passengers, had become increasingly outdated. Japanese Airlines and Inter-carrier Agreement of International Air Transport Association in 1995 has been adopted the unlimited liability of air carrier in international flight. The IATA Inter-Carrier Agreement, in which airlines in international air transportation agree to waive the limit of damages, was long and hard in coming, but it was remarkable achievement given the political and economic realities of the world. IATA deserves enormous credit for bringing it about. The Warsaw System is controversial and questionable. In order to find rational solution to disputes between nations which adopted differing liability systems in international air transportation, we need to reform the liability of air carriers the 'Warsaw system' and fundamentally, to unify the liability system among the nations. The International Civil Aviation Organization(ICAO) will therefore reinforce its efforts to further promote a legal environment that adequately reflects the public interest and the needs of the parties involved. The ICAO Study Group met in April, 1998, together with the Drafting Committee. The time between the "Special Group on the Modernization and Consolidation of the 'Warsaw system'(SGMW)" and the Diplomatic Conference must be actively utilized to arrange for profound studies of the outstanding issues and for wide international consultations with a view to narrowing the scope of differences and preparing for a global international consensus. From 11 to 28 May 1999 the ICAO Headquarters at Montreal hosted a Diplomatic Conference convened to consider, with a view to adoption, a draft Convention intended to modernize and to integrate replace the instruments of the Warsaw system. The Council of ICAO convened this Conference under the Procedure for the Adoption of International Conventions. Some 525 participants from 121 Contracting States of ICAO attended, one non-contracting State, 11 observer delegations from international organizations, a total of 544 registered participants took part in the historic three-week conference which began on 10 May. The Conference was a success since it adopted a new Convention for the Unification of Certain Rules for International Carriage by Air. The 1999 Montreal Convention, created and signed by representatives of 52 countries at an international conference convened by ICAO at Montreal on May 28, 1999, came into effect on November 4, 2003. Representatives of 30 countries have now formally ratified the Convention under their respective national procedures and ratification of the United States, which was the 30th country to ratify, took place on September 5, 2003. Under Article 53.6 of the Montreal Convention, it enters into force on the 60th day following the deposit of the 30th instrument of ratification or acceptation. The United States' ratification was deposited with ICAO on September 5, 2003. The ICAO have succeeded in modernizing and consolidating a 70-year old system of international instruments of private international law into one legal instrument that will provide, for years to come, an adequate level of compensation for those involved in international aircraft accidents. An international diplomatic conference on air law by ICAO of 1999 succeeded in adopting a new regime for air carrier liability, replacing the Warsaw Convention and five other related legal instruments with a single convention that provided for unlimited liability in relation to passengers. Victims of international air accidents and their families will be better protected and compensated under the new Montreal Convention, which modernizes and consolidates a seventy-five year old system of international instruments of private international law into one legal instrument. A major feature of the new legal instrument is the concept of unlimited liability. Whereas the Warsaw Convention set a limit of 125,000 Gold Francs (approximately US$ 8,300) in case of death or injury to passengers, the Montreal Convention introduces a two-tier system. The first tier includes strict liability up to l00,000 Special Drawing Rights (SDR: approximately US$ 135,000), irrespective of a carrier's fault. The second tier is based on presumption of fault of a carrier and has no limit of liability. The 1999 Montreal Convention also includes the following main elements; 1. In cases of aircraft accidents, air carriers are called upon to provide advance payments, without delay, to assist entitled persons in meeting immediate economic needs; the amount of this initial payment will be subject to national law and will be deductable from the final settlement; 2. Air carriers must submit proof of insurance, thereby ensuring the availability of financial resources in cases of automatic payments or litigation; 3. The legal action for damages resulting from the death or injury of a passenger may be filed in the country where, at the time of the accident, the passenger had his or her principal and permanent residence, subject to certain conditions. The new Montreal Convention of 1999 included the 5th jurisdiction - the place of residence of the claimant. The acceptance of the 5th jurisdiction is a diplomatic victory for the US and it can be realistically expected that claimants' lawyers will use every opportunity to file the claim in the US jurisdiction - it brings advantages in the liberal system of discovery, much wider scope of compensable non-economic damages than anywhere else in the world and the jury system prone to very generous awards. 4. The facilitation in the recovery of damages without the need for lengthy litigation, and simplification and modernization of documentation related to passengers. In developing this new Montreal Convention, we were able to reach a delicate balance between the needs and interests of all partners in international civil aviation, States, the travelling public, air carriers and the transport industry. Unlike the Warsaw Convention, the threshold of l00,000 SDR specified by the Montreal Convention, as well as remaining liability limits in relation to air passengers and delay, are subject to periodic review and may be revised once every five years. The primary aim of unification of private law as well as the new Montreal Convention is not only to remove or to minimize the conflict of laws but also to avoid conflict of jurisdictions. In order to find a rational solution to disputes between nations which have adopted differing liability systems in international air transport, we need fundamentally to reform their countries's domestic air law based on the new Montreal Convention. It is a desirable and necessary for us to ratify rapidly the new Montreal Convention by the contracting states of lCAO including the Republic of Korea. According to the Korean and Japanese ideas, airlines should not only pay compensation to passengers immediately after the accident, but also the so-called 'condolence' money to the next of kin. Condolence money is a gift to help a dead person's spirit in the hereafter : it is given on account of the grief and sorrow suffered by the next of kin, and it has risen considerably over the years. The total amount of the Korean and Japanese claims in the case of death is calculated on the basis of the loss of earned income, funeral expenses and material demage (baggage etc.), plus condolence money. The economic and social change will be occurred continuously after conclusion of the new Montreal Convention. In addition, the real value of life and human right will be enhanced substantially. The amount of compensation for damage caused by aircraft accident has increased in dollar amount as well as in volume. All air carrier's liability should extend to loss of expectation of leisure activities, as well as to damage to property, and mental and physical injuries. When victims are not satisfied with the amount of the compensation for damage caused by aircraft accident for which an airline corporation is liable under the current liability system. I also would like to propose my opinion that it is reasonable and necessary for us to interpret broadly the meaning of the bodily injury on Article 17 of the new Montreal Convention so as to be included the mental injury and condolence. Furthermore, Korea and Japan has not existed the Air Transport Act regulated the civil liability of air carrier such as Air Transport Act (Luftverkehrsgestz) in Germany. It is necessary for us to enact "the Korean Air Transport Contract Act (provisional title)" in order to regulate the civil liability of air carrier including the protection of the victims and injured persons caused by aircraft accident.
Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.
The sprig of Jinryungtang Gagambang has been used for curing as a traditional medicine without any experimental evidence to support the rational basis for their clinical use. This experiment was carried out to evaluate the possible therapeutic or antitumoral effects of Jinryungtang Gagambang extract against cancer, and to study some mechanisms responsible for its effect. The cytotoxic and antitumor effects were evaluated on human cell liens (A549, hep3B, Caki-1, Sarcoma 180) after exposure to Jinryungtang Gagambang extract using in ILS, colony forming efficency and SRB assay which were regarded as a valuable method for cytotoxic and antitumor effects of unknown compound on tumor cell lines. The results obtained in this studies were as follows. 1. As a result of exposure to Jinryungtang Gagambang extract, the proliferation of A549, hep3B, Caki-1, good correlations were shown from the results of SRB assay and those of clogenetic assay. 2. The oral administration of Jinryungtang Gagambang extract showed significant effects of increase of MST(mean survival time) and ILS(increased life span) depending on the increasing concentration. 3. Against squamous cell carcinoma induced by MCA, Jinryungtang Gagambang decreased not only the frequency of tumor production but also the number and weight of tumors per tumor bearing mice(TBM). Jinryungtang Gagambang also significantly suppressed the development of 3LL cell-implanted tumors by frequency and their size, and some developed tumors were regressed by the continuous treatment of Jinryungtang Gagambang extract into TBM. 4. Jinryungtang Gagambang extract also increased NK cell activities. According to the above results, it could be suggested that Jinryungtang Gagambang extract has prominent antiutmor effect.