• Title/Summary/Keyword: 방현재

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Activation of NF-${\kappa}B$ in Lung Cancer Cell Lines in Basal and TNF-${\alpha}$ Stimulated States (폐암 세포에서 기저 상태와 TNF-${\alpha}$ 자극 시 NF-${\kappa}B$의 활성화)

  • HwangBo, Bin;Lee, Seung-Hee;Lee, Choon-Taek;Yoo, Chul-Gyu;Han, Sung-Koo;Shim, Young-Soo;Kim, Young-Whan
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.5
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    • pp.485-496
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    • 2002
  • Background : The NF-${\kappa}B$ transcription factors control various biological processes including the immune response, acute phase reaction and cell cycle regulation. NF-${\kappa}B$ complexes are retained in the cytoplasm in the basal state and various stimuli cause a translocation of the NF-${\kappa}B$ complexes into the nucleus where they bind to the ${\kappa}B$ elements and regulate the transcription of the target genes. Recent reports also suggest that NF-${\kappa}B$ proteins are involved in oncogenesis, tumor growth and metastasis. High expression of NF-${\kappa}B$ expression was reported in many cancer cell lines and tissues. The constitutive activation of NF-${\kappa}B$ was also reported in several cancer cell lines supporting its role in cancer development and survival. The anti-apoptotic action of NF-${\kappa}B$ is important for cancer survival. NF-${\kappa}B$ also controls the expression of several proteins that are important for cellular adhesion (ICAM-1, VCAM-1) suggesting a role in cancer metastasis. In lung cancer, high expression levels of the NF-${\kappa}B$ subunit p50 and c-Rel were reported. In fact, high expression does not mean a high activity, and the activation pattern of NF-${\kappa}B$ in lung cancer has not been reported. Materials and Methods : In this study, the NF-${\kappa}B$ nuclear binding activity in the basal and TNF-${\alpha}$ stimulated states were exmined in various lung cancer cell lines and compared with the normal bronchial epithelial cell line. Twelve lung cancer cell lines including the non-small cell and small cell lung cancer cell lines (A549, NCI-H358, NCI-H441, NCI-H552, NCI-H2009, NCI-H460, NCI-H1229, NCI-H1703, NCI-H157, NCI-H187, NCI-H417, NCI-H526) and BEAS-2B bronchial epithelial cell line were used. To evaluate the NF-${\kappa}B$ expression and DNA binding activity, western blot analysis and an electrophoretic mobility shift assay with the nuclear protein extracts. Results : The basal expressions of the p65 and p50 subunits were observed in the BEAS-2B cell line and all lung cancer cell lines except for NCI-H358 and NCI-H460. The expression levels of p65 and p50 were increased 30 minutes after stimulation with TNF-${\alpha}$ in BEAS-2B and in 10 lung cancer cell lines. In the NCI-H358 and NCI-H460 cell lines, p65 expression was not observed in the basal and stimulated states and the two p50 related protein levels were higher after stimulation with TNF-${\alpha}$ These new proteins were smaller than p50 and are thought to be variants of p50. In the basal state, NF-${\kappa}B$ was nearly activated in the BEAS-2B and all lung cancer cell lines. The DNA binding activity of the NF-${\kappa}B$ complexes was markedly higher after stimulation with TNF-${\alpha}$ In the BEAS-2B and all lung cancer cell line except for NCI-H358 and NCI-H460, the activated NF-${\kappa}B$ complex was a p65/p50 heterodimer. In the NCI-H358 and NCI-H460 lung cancer cell lines, the NF-${\kappa}B$ complex was variant of a p50/p50 homodimer. Conclusion : The NF-${\kappa}B$ activation pattern in the lung cancer cell lines and the normal bronchial epithelial cell lines was similar except for the activation of a variant of the p50/p50 homodimer in some lung cancer cell linse.

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 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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A Study on Rationalization of National Forest Management in Korea (국유림경영(國有林經營)의 합리화(合理化)에 관(關)한 연구(硏究))

  • Choi, Kyu-Ryun
    • Journal of Korean Society of Forest Science
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    • v.20 no.1
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    • pp.1-44
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    • 1973
  • Needless to say, the management of national forest in all countries is very important in view of the national mission and management purposes. Korean national forest is also in particular significant in promoting national economy for the continuous increasing of the demand for wood, conservation of the land and social welfare. But there's no denying the fact that the leading aim of the Korean forest policy has been based upon the conservation of forest resources and recovery of land conservation function instead of improvement of the forest productive capacity. Therefore, the management of national forest should be aimed as an industry in the chain of the Korean national economy. And the increment of the forest productive capacity based on rationalized forest management is also urgently needed. Not only the increment of the timber production but also the establishment of the good forest in quality and quantity are to bring naturally many functions of conservation and other public benefits. In 1908 Korean national forest was historically established for the first time as a result of the notification for ownership, and was divided into two kinds in 1911-1924, such as indisposable national forest for land conservation, forest management, scientific research and public welfare, and the other national forest to be disposed. Indisposable forest is mostly under the jurisdiction of national forest stations (Chungbu, Tongbu, Nambu), and the tother national forests are under custody of respective cities and provinces, and under custody of the other government authorities. As of the end of 1971, national forest land is 19.5% (1,297,708 ha) of the total forest land area, but growing stock is 50.1% ($35,406,079m^3$) of the total forest growing stock, and timber production of national forest is 23.6% ($205,959m^3$) of the year production of total timber in Korea. Accordingly, it is the important fact that national forest occupies the major part of Korean forestry. The author positively affirms that success or failure of the management of national forest controls rise or fall of forestry in Korea. All functions of forest are very important, but among others the function of timber production is most important especially in Korea, that unavoidably imports a large quantity of foreign wood every year (in 1971 import of foreign wood-$3,756,000m^3$, 160,995,000 dollars). So, Korea urgently needs the improvement of forest productive capacity in national forest. But it is difficult that wood production meets the rapid increase of demand for wood to the development of economy, because production term of forestry is long, so national forest management should be rationalized by the effective investment and development of forestry techniques in the long view. Although Korean national forest business has many difficulties in the budget, techniques and the lack of labour due to outflow of rural village labour by development of national economy, and the increase of labour wages and administrative expenses etc. the development of national forest depends on adoption of the suitable forest techniques and management adapted for social and economical development. In this view point the writer has investigated and analyzed the status of the management of national forest in Korea to examine the irrational problems and suggest an improvement plan. The national forestry statistics cited in this study is based on the basic statistics and the statistics of the forest business as of the end of 1971 published by Office of Forestry, Republic of Korea, and the other depended on the data presented by the national forest stations. The writer wants to propose as follows (seemed to be helpful in improvement of Korean national forest management). 1) In the organization of national forest management, more national forest stations should be established to manage intensively, and the staff of working plan officials should be strengthened because of the importance of working plan. 2) By increasing the staff of protection officials, forest area assigned for each protection official should be decreased to 1,000-2,000 ha. 3) The frequent personnel changes of supervisor of national forest station(the responsible person on-the-spot) obstructs to accomplish the consistent management plan. 4) In the working plan drafting for national forest, basic investigations should be carefully practiced with sufficient expenditure and staff not to draft unreal working plan. 5) The area of working-unit should be decreased to less than 2,000 ha on the average for intensive management and the principle of a working-unit in a forest station should be realized as soon as possible. 6) Reforestation on open land should be completed in a short time with a debt of the special fund(a long term loan), and the land on which growing hardwood stands should be changed with conifers to increase productivity per unit area, and at the same time techical utilization method of hardwood should be developed. 7) Expenses of reforestation should be saved by mechanization and use of chemicals for reforestation and tree nursery operation providing against the lack of labour in future. 8) In forest protection, forest fire damage is enormous in comparison with foreign countries, accordingly prevention system and equipment should be improved, and also the minimum necessary budget should be counted up for establishment and manintenance of fire-lines. 9) Manufacture production should be enlarged to systematize protection, processing and circulation of forest business, and, by doing this, mich benefit is naturally given for rural people. 10) Establishment and arrangement of forest road networks and erosion control work are indispensable for the future development of national forest itself and local development. Therefore, these works should be promoted by the responsibility of general accounting instead of special accounting. 11) Mechanization of forest works should be realized for exploiting hinterlands to meet the demand for timber increased and for solving lack of labour, consequently it should promote import of forest machines, home production, training for operaters and careful adminitration. 12) Situation of labour in future will grow worse. Therefore, the countermeasure to maintain forest labourers and pay attention to public welfare facilities and works should be considered. 13) Although the condition of income and expenditure grows worse because of economical change, the regular expenditure should be fixed. So part of the surplus fund, as of the end of 1971, should be established for the fund, and used for enlarging reforestation and forest road networks(preceding investment in national forest).

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