• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.823-834
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• 1998

Background: Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica; they liberate the pro-inflammatory cytokines such as IL-1$\beta$, IL-6, TNF-$\alpha$ and fibrogenic cytokines, TGF-$\beta$ and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGF-$\beta$, a fibrogenic cytokine, have not been defined, yet. In this study, we investigated silica induced IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ production and the effect of IL-1$\beta$, IL-6, TNF-$\alpha$ on the production of TGF-$\beta$ from lung macrophages of Balb/C mice. Method: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica ($SiO_2$) in the various concentration for 2, 4, 8, 12, and 24 hours. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. Results: The production of IL-6 was not observed till 4 hours, and reached the peak levels at 8 hours after stimulation of silica. The production of TNF-$\alpha$ increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-$\beta$ production reached the peak levels at 24 hours. TNF-$\alpha$ upregulated the silica induced TGF-$\beta$ production. Silica induced TGF-$\beta$ production was blocked by pretreated anti-TNF-$\alpha$ antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours TNF-$\alpha$ and 12 hours in TGF-$\beta$. Conclusion: The results above suggest that silica induced the sequential production of IL-6, 1NF-$\alpha$ and TGF-$\beta$ from macrophages and TNF-$\alpha$ upregultaes the production of TGF-$\beta$ from silica-induced macrophages.

• Journal of Chest Surgery
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• v.36 no.9
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• pp.651-658
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• 2003

Since the first implanted in September 1997, the use of On-X prosthetic heart valve has been increasing around in the world. This study was designed to assess the feasibility, safety, and the postoperative hemodynamics with this new valve in clinical setting. Material and Method: The current study was carried out on 52 patients undergoing aortic valve replacement with this prosthesis between April 1999 to August 2002 at Chonnam National University Hospital to evaluate the surgical results. 52％ of the patients were male and the average age at implant was 50$\pm$13 years. The study followed the guidelines of the AATS/STS. Preoperatively, 32(61.5％) patients were in NYHA functional class III or IV and 2 patients had previous aortic valve surgery. Concomitant cardiac surgery was performed in 71.1％. The implanted valve sizes were 19 mm in 13 patients, 21 mm in 26, 23 mm in 10 and 25 mm in 3, respectively. Mean follow-up was 16.6$\pm$10.5 months (1∼39 months). Echocardiographic assessment was performed pre- and immediate postoperatively, as well as 3, 6, 12 months after surgery, evaluating pressure loss and regression of left ventricular hypertrophy. Result: Mean cardiopulmonary bypass time was 191$\pm$94.7 minutes with an aortic cross-clamp time of 142$\pm$51.7 minutes. There was no early and late mortality, Freedom from adverse events at 1 year in the study were as follows: thromboembolism, 95.6$\pm$6％; bleeding events, 90.2$\pm$4％; paravalvular leakage 92.3$\pm$4％; and overall valve-related morbidity at 1 year was 76.6$\pm$3％. There were no cases of valve thrombosis, prosthetic valve endocarditis and structural or non-structural failure. Left ventricular function at 12 months after surgery (EF=62.7$\pm$9.8％) revealed a statistically significant improvement compared to preoperative investigation (EF=55.8$\pm$15.9％, p=0.006). Left ventricular mass index was 247.3$\pm$122.3 g/$m^2$ on preoperative echocardiographic study, but regressed to 155.5$\pm$58.2 g/$m^2$ at postoperative 1 year (p=0.002). Over the follow-up period a further decrease of peak transvalvular gradients was observed in all patients: 62.5$\pm$38.0 mmHg on preoperative assessment, 18.2$\pm$6.8 mmHg at immediate postoperative period (p < 0.0001), 7.6$\pm$5.09 mmHg (p<0.0001) at 6 month, 18.0$\pm$10.8 mmHg (p<0.0001) at 1 year. Conclusion: The On-X prosthetic heart valve performs satisfactorily in the first 1 year period. Clinical outcome by examining NYHA functional classification revealed especially good results. Effective regression of left ventricular hypertrophy and statistically significant decrease of transvalvular gradient were observed over the first year, but longer-term follow-up of this patient group is needed to establish the expected rates for late valve-related events as well as the long-term clinical efficacy of this valve.

• Tuberculosis and Respiratory Diseases
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• v.40 no.3
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• pp.213-222
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• 1993

Background : Bronchial asthma has been known as an inflmmatory disease. There have been many evidences that polymorphonuclear leukocytes (PMN) might play an important role in the pathogrnesis of asthma. Although many investigators suggested that pneumocyte injury by PMN-derived oxygen radicals may contribute to the pathogenesis of asthma, there has been few report for a direct evidence of oxygen radicals-mediated pneumocyte injury in bronchial asthma. Furthermore the exact mechanism of oxygen radicals-mediated pneumocyte injury is still controversy. This study was designed to establish a direct in vitro evidence and its clinical significance of pneumocyte injury by PMN-derived superoxide anion in bronchial asthma and to elucidate the main mechanism of superoxide anion-mediated pneumocyte injury. Methods : 12 stable asthmatics and 5 healthy volunteers were participated in this study. PMN was separated from peripheral venous blood samples by using dextran sedimentation and Ficoll-Hypaque density gradient separation method. Superoxide anion productions by PMN and plasma SOD activities were measured by spectrophotometric assay using the principle of SOD inhibitable cytochrome c reduction. PMN-mediated pneumocyte injuries were measured by $^{51}Cr$-release assay using A549 pneumocytes and were expressed as percent lysis and percent detachment. Results: 1) PMN from asthmatics produced more amount of superoxide anion compared to PMN from normal subjects ($6.65{\pm}0.58$ vs $2.81{\pm}0.95\;nmol/1{\times}10^6$ cells, p<0.05), and showed an inverse correlation with $FEV_1$(R=-0.63, p<0.05), but no correlation with $PC_{20}$ histamine in asthmatics. 2) Plasma SOD activities were decreased in asthmatics compared to normal subjects but not significant, and showed a positive correlation with $FEV_1$(R=0.63, p<0.05) but no correlation with $PC_{20}$ histamine in asthmatics. 3) There were a positive correlation between plasma SOD activity and superoxide anion production by PMN in normal subjects (R=0.88, p<0.05) but not in asthmatics. 4) PMN-mediated pneumocyte injury was predominantly expressed as cell detachment rather than cell lysis in both groups, and PMN from asthmatics showed more potent cytotoxic effect on A549 pneumocytes compated to PMN from normal subjects. PMN-mediated detachment rather than lysis of A549 pneumocytes was significantly inhibited by in vitro SOD but not by diluted serum. 5) PMN-mediated detachment rather than lysis of A549 pneumocytes showed a good correlation with superoxide anion production by PMN (R=0.90 in normal subjects, R=0.82 in asthmatics, p<0.05) but no correlation with plasma SOD activity. PMN-mediated pneumocyte injuries were not correlated with $FEV_1$ or $PC_{20}$ histamine in asthmatics. 6) There were no significant differences in PMN-mediated pneumocyte injuries between allergic and nonallergic asthmatics. Conclusion : Our results suggest that pneumocyte injury by PMN-derived superoxide anion may partially contribute to the pathogenesis of asthma and that cell detachment rather than cell lysis may be the mechanism of superoxide anion-mediated pneumocyte injury.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.862-870
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• 1995

Background: Oxygen free radicals have generally been considered as cytotoxic agents. On the other hand, recent results suggest that small nontoxic amounts of these radicals may act a role in intracellular signal transduction pathway and many efforts to reveal the role of these radicals as secondary messengers have been made. It is evident that the oxygen radicals are released by various cell types in response to extracellular stimuli including LPS, TNF, IL-1 and phorbol esters, all of which translocate the transcription factor $NF{\kappa}B$ from cytoplasm to nucleus by releasing an inhibitory protein subunit, $I{\kappa}B$. Activation of $NF{\kappa}B$ is mimicked by exposure to mild oxidant stress, and inhibited by agents that remove oxygen radicals. It means the cytoplasmic form of the inducible tanscription factor $NF{\kappa}B$ might provide a physiologically important target for oxygen radicals. At the same time, it is well known that LPS induces the release of oxygen radicals in neutrophil with the activation of $NF{\kappa}B$. From above facts, we can assume the expression of IL-8 and IL-$1{\beta}$ gene by LPS stimulation may occur through the activation of $NF{\kappa}B$, which is mediated through the release of $I{\kappa}B$ by increasing amounts of oxygen radicals. But definitive evidence is lacking about the role of oxygen free radicals in the expression of IL-8 and IL-$1{\beta}$ gene in mononuclear phagocytic cells. We conducted a study to determine whether oxygen radicals act a role in the expression of IL-8 and IL-$1{\beta}$ gene in mononuclear phagocytic cells. Method: Human peripheral blood monocytes were isolated from healthy volunteers. Time and dose relationship of $H_2O_2$-induced IL-8 and IL-$1{\beta}$ mRNA expression was observed by Northern blot analysis. To evaluate the role of oxygen radicals in the expression of IL-8 and IL-$1{\beta}$ mRNA by LPS stimulation, pretreatment of various antioxiants including PDTC, TMTU, NAC, ME, Desferrioxamine were done and Northern blot analysis for IL-8 and IL-$1{\beta}$ mRNA was performed. Results: In PBMC, dose and time dependent expression of IL-8 and IL-$1{\beta}$ mRNA by exogenous $H_2O_2$ was not observed. But various antioxidants suppressed the expression of LPS-induced IL-8 and IL-$1{\beta}$ mRNA expression of PBMC and the suppressive activity was most prominant when the pretreatment was done with TMTU. Conclusion: Oxygen free radical may have some role in the expression of IL-8 and IL-$1{\beta}$ mRNA of PBMC but that radical might not be $H_2O_2$.

• Journal of the Korean association of regional geographers
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• v.3 no.2
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• pp.37-87
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• 1997

As a results of researches on the cultivation processes and settlement developments on the Mangyoung river valley as a whole could be have four 'Space-Time Continuity' through a [Origin-Destination] theory model. On a initial phases of cultivation, the cultivation process has been begun at mountain slopes and tributory plains in upper part of river-basin from Koryo Dynasty to early Chosun Dynasty. At first, indigenous peasants burned forests on the mountain slopes for making 'dryfield' for a cereal crops. Following population increase more stable food supply is necessary facets of life inducing a change production method into a 'wetfield' in tributory plains matching the population increase. First sedentary agriculture maybe initiated at this mountain slopes and tributory plains on upper part of river basin through a burning cultivation methods. Mountain slopes and tributory plains are become a Origin area in cultivation processes. It expanded from up to down through the valleys with 'a bits of land' fashion in a steady pace like a terraced fields expanded with bit by bit of land to downward. They expanded their land to the middle part of river basin in mid period of Chosun Dynasty with dike construction techniques on the river bank. Lower part of river cultivated with embankment building techniques in 1920s and then naturally expanded to the tidal marshes on the estuaries and river inlets of coastal areas. 'Pioneer fringes' are consolidated at there in modern times. Changes in landscapes are appeared it's own characters with each periods of time. Followings are results of study through the Mangyoung river valley as a whole. (1) Mountain slopes and tributory plains on the upper part of river are cultivated 'dryfields' by indigenous peasants with Burning cultivation methods at first and developed sedentary settlements at the edges of mountain slopes and on the river terrace near the fields. They formed a kind of 'periphery-located cluster type' of settlement. This type of settlement are become a prominant type in upper part of river basin. 'Dryfields' has been changed into a 'wetfields' at the narrow tributory plains by increasing population pressure in later time. These wetfields are supplied water by Weir and Ponds Irrigation System(제언수리방법). Streams on the tributory plains has been attracted wetfields besides of it and formed a [water+land] complex on it. 'Wetfields' are expanded from up to downward with a terraced land pattern(adder like pattern, 붕전) according to the gradient of valley. These periphery located settlements are formed a intimate ecological linkage with several sets of surroundings. Inner villages are expanded to Outer villages according to the expansion of arable lands into downward. (2) Mountain slopes and tributory plains expanded its territory to the alluvial deposited plains on the middle part of river valley with a urgent need of new land by population increase. This part of alluvial plains are cultivated mainly in mid period of Chosun Dynasty. Irrigation methods are changed into a Dike Construction Irrigation method(천방수리방법) for the control of floods. It has a trend to change the subjectives of cultivation from community-oriented one who constructed Bochang along tributories making rice paddies to local government authorities who could be gather large sums of capitals, techniques and labours for the big dike construction affairs. Settlements are advanced in the midst of plains avoiding friction of distances and formed a 'Centrallocated cluster type' of settlements. There occured a hierarchical structures of settlements in ranks and sizes according merits of water supply and transportation convenience at the broad plains. Big towns are developed at there. It strengthened a more prominant [water+land] complex along the canals. Ecological linkages between settlements and surroundings are shaded out into a tiny one in this area. (3) It is very necessary to get a modern technology of flood control at the rivers that have a large volume of water and broad width. The alluvial plains are remained in a wilderness phase until a technical level reached a large artificial levee construction ability that could protect the arable land from flood. Until that time on most of alluvial land at the lower part of river are remained a wilderness of overgrown with reeds in lacks of techniques to build a large-scale artificial levee along the riverbank. Cultivation processes are progressed in a large scale one by Japanese agricultural companies with [River Rennovation Project] of central government in 1920s. Large scale artificial levees are constructed along the riverbank. Subjectives of cultivation are changed from Korean peasants to Japanese agricultural companies and Korean peasants fell down as a tenant in a colonial situation of that time in Korea. They could not have any voices in planning of spatial structure and decreased their role in planning. Newly cultivated lands are reflected company's intensions, objectives and perspectives for achieving their goals for the sake of colonial power. Newly cultivated lands are planned into a regular Rectangular Block settings of rice paddies and implanted a large scale Bureaucratic-oriented Irrigation System on the cultivated plains. Every settlements are located in the midst of rice paddies with a Central located Cluster type of settlements. [water+land] complex along the canal system are more strengthened. Cultivated space has a characters of [I-IT] landscapes. (4) Artificial levees are connected into a coastal emnankment for a reclamation of broad tidal marshes on the estuaries and inlets of rivers in the colonial times. Subjectives of reclamation are enlarged into a big agricultural companies that could be acted a role as a big cultivator. After that time on most of reclamation project of tidal marshes are controlled by these agricultural companies formed by mostly Japanese capitalists. Reclaimed lands on the estuaries and river inlets are under hands of agricultural companies and all the spatial structures are formed by their intensions, objectives and perspectives. They constructed a Unit Farming Area for the sake of companies. Spatial structures are planned in a regular one with broad arable land for the rice production of rectangular blocks, regular canal systems and tank reservoir for the irrigation water supply into reclaimed lands. There developed a 'Central-located linear type' of settlements in midst of reclaimed land. These settlements are settled in a detail program upon this newly reclaimed land at once with a master plan and they have planned patterns in their distribution, building materials, location, and form. Ecological linkage between Newly settled settlemrnts and its surroundings are lost its colours and became a more artificial one by human-centred environment. [I-IT] landscapes are become more prominant. This region is a destination area of [Origin-Destination] theory model and formed a 'Pioneer Fringe'. It is a kind of pioneer front that could advance or retreat discontinously by physical conditions and socio-cultural conditions of that region.