• Journal of Chest Surgery
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• v.35 no.1
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• pp.1-10
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• 2002

Background: Despite the relatively high mortality rates in the chronic heart failure model induced by coronary artery ligation are relatively high, this model has been a subject of continuos research because of its clinical correlation. Chronic heart failure model of large-sized animals is very useful to analyse mechanical or biological effects on circulatory system which is difficult in small-sized animals. The purpose of this study is to establish the heart failure model by coronary artery ligation in sheep. Material and Method: Among 9 Corridale sheep, the homonymous artery and the diagonal branch were ligated simultaneously in 2 sheep and remaining 7 sheep were assigned to successive ligation of both arteries at an interval of 1 hour. Both coronary arteries were ligated from the point 40% proximal to the apex of the heart. Hemodynamic and echocardiographic parameters were analyzed before the ligation of the coronary artery, after the ligation of the homonymous artery, and after additional ligation of the diagonal branch. The experimental animals were sacrificed after 2 or 3 months of growth and histopathologic studies were performed Result: Immediate postoperative death occurred in the 2 sheep that had received simultaneous ligation of the homonymous artery and diagonal branch. On the other hand, all the 7 sheep that were lifated in succession were survived up to 3 months. Arterial pressure was sifnificantly decreased immediately after ligation of the homonymous artery(p<0.05), and the cardiac output was decreased and pulmonary capillary wedge pressure was increased after further ligation of the diagonal branch(p<0.05). Central venous pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, left ventricular end-diastolic dimension and end-systolic dimension were markedly increased 3 months after ligation of coronary arteries. Anteroseptal akinesia or dyskinesia was developed after the ligation of coronary arteries. Histopathologic study revealed we]1-demarcated ischemic area of fibrosis. Conclusion: Using methods of successive ligation of the homonymous artery and diagonal branch, chronic heart failure model could be reliably established in sheep.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1972.03a
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• pp.6-7
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• 1972

The air pollutants can be classified into the irritant gas and the asphixation gas, and the irritant gas is closely related to the otorhinolaryngological diseases. The common irritant gases are nitrogen oxides, sulfur oxides, hydrogen carbon compounds, and the potent and irritating PAN (peroxy acyl nitrate) which is secondarily liberated from photosynthesis. Those gases adhers to the mucous membrane to result in ulceration and secondary infection due to their potent oxidizing power. 1. Sulfur dioxide gas Sulfur dioxide gas has the typical characteristics of the air pollutants. Because of its high solubility it gets easily absorbed in the respiratory tract, when the symptoms and signs by irritation become manifested initially and later the resistance in the respiratory tract brings central about pulmonary edema and respiratory paralysis of origin. Chronic exposure to the gas leads to rhinitis, pharyngitis, laryngitis, and olfactory or gustatory disturbances. 2. Carbon monoxide Toxicity of carbon monoxide is due to its deprivation of the oxygen carrying capacity of the hemoglobin. The degree of the carbon monoxide intoxication varies according to its concentration and the duration of inhalation. It starts with headache, vertigo, nausea, vomiting and tinnitus, which can progress to respiratory difficulty, muscular laxity, syncope, and coma leading to death. 3. Nitrogen dioxide Nitrogen dioxide causes respiratory disturbances by formation of methemoglobin. In acute poisoning, it can cause pulmonary congestion, pulmonary edema, bronchitis, and pneumonia due to its strong irritation on the eyes and the nose. In chronic poisoning, it causes chronic pulmonary fibrosis and pulmonary edema. 4. Ozone It has offending irritating odor, and causes dryness of na sopharyngolaryngeal mucosa, headache and depressed pulmonary function which may eventually lead to pulmonary congestion or edema. 5. Smog The most outstanding incident of the smog occurred in London from December 5 through 8, 1952, because of which the mortality of the respiratory diseases increased fourfold. The smog was thought to be due to the smoke produced by incomplete combustion and its byproduct the sulfur oxides, and the dust was thought to play the secondary role. In new sense, hazardous is the photochemical smog which is produced by combination of light energy and the hydrocarbons and oxidant in the air. The Yonsei University Institute for Environmental :pollution Research launched a project to determine the relationship between the pollution and the medical, ophthalmological and rhinopharyngological disorders. The students (469) of the "S" Technical School in the most heavily polluted area in Pusan (Uham Dong district) were compared with those (345) of "K" High School in the less polluted area. The investigated group had those with subjective symptoms twice as much as the control group, 22.6% (106) in investigated group and 11.3% (39) in the control group. Among those symptomatic students of the investigated group. There were 29 with respiratory symptoms (29%), 22 with eye symptoms (21%), 50 with stuffy nose and rhinorrhea (47%), and 5 with sore thorat (5%), which revealed that more than half the students (52%) had subjective symptoms of the rhinopharyngological aspects. Physical examination revealed that the investigated group had more number of students with signs than those of the control group by 10%, 180 (38.4%) versus 99 (28.8%). Among the preceding 180 students of the investigated group, there were 8 with eye diseases (44%), 1 with respiratory disease (0.6%), 97 with rhinitis (54%), and 74 with pharyngotonsillitis (41%) which means that 95% of them had rharygoical diseases. The preceding data revealed that the otolaryngological diseases are conspicuously outnumbered in the heavily polluted area, and that there must be very close relationship between the air pollution and the otolaryngological diseases, and the anti-pollution measure is urgently needed.

• 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 Environmental Health Sciences
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• v.43 no.1
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• pp.1-22
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• 2017

'The worstest environment disaster', 'World's first biocide massacre', 'Home-based Sewol ferry disaster' are all phrases attached to the recent humidifier disinfectant disaster. In the spring of 2011, four of 8 pregnant women including 1 adult man passed away at a university hospital in Seoul due to breathing failure. Epidemiologic investigation conducted by the Korean CDC soon revealed the inhalation of humidifier disinfectant, which had been widely used in Korea during the winter, to be responsible for the disease. As well as lung fibrosis hardening of the lungs, other diseases including asthma, rhinitis, skin disease, liver disease, fetal disease or cancers have been researched for their relation with exposure to the products. By February 9, 2017, 5,342 cases had registered for health problems and 1,131 of them were already dead (20.8% mortality rate). Based on studies by government agencies and a telephone survey of the general population by Seoul National University and civic groups, around 20% of the general public of Korea has used these products. Since the market release of the first product by SK Chemical in 1994, over 7.1 million items from around 20 brands were sold up to 2011. Most of the products were manufactured by well-known large conglomerates such as SK, Lotte, Samsung, Shinsegye, LG, and GS, as well as some European companies including UK-based Reckitt Benckiser and TESCO, the German firm Henkel, the Danish firm KeTox, and an Irish company. Even though this disaster was unveiled in 2011 by the Korean government, the issue of the victims was neglected for over five years. In 2016, an unexpected but intensive investigation by prosecutors found that Reckitt Benckiser manipulated and concealed animal tests for its own brand and brought several university experts and company employees to court. The matter was an intense social issue in Korea from May to June with a surge in media coverage. The prosecutor's investigation and a nationwide boycott campaign organized by victims and environmental groups against Reckitt Benckiser, whose product had been used by more than 70% of victims, led to the producer's official apology and a compensation scheme. A legislative investigation organized after the April 2016 national election revealed the producers' faults and the government's responsibility, but failed to meet expectations. A special law for the victims passed the National Assembly in January 2017 and a punitive system together with a massive environmental epidemiology investigation are expected to be the only solutions for this tragedy. Sciences of medicine, toxicology and environmental health have provided decisive evidence so far, but for the remaining problems the perspectives of social sciences such as sociology and jurisprudence are highly necessary, similar to with the Minamata disease and Wonjin Rayon events. It may not be easy to follow this issue using unfamiliar terminology from medical and chemical science and the long, complicated history of the event. For these reasons the author has attempted to write this article in a question and answer format to render it easier to follow. The 17 questions are: Q1 What is humidifier disinfectant? Q2 What kind of health problems are caused by humidifier disinfectant? Q3 How many victims are there? Q4 What is the analysis of the 1,112 cases of death? Q5 What is the problem with the government's diagnostic criteria and the solution? Q6 Who made what brands? Q7 Has there been a recall? What is still on sale? Q8 Was safety not checked by any producers? Q9 What are the government's responsibilities? Q10 Is it true that these products were sold only in Korea? Q11 Why and how was it unveiled only in 2011 after 17 years of sales? Q12 What delayed the resolution of the victim issue? Q13 What is the background of the prosecutor's investigation in early 2016? Q14 Is it possible to report new victim cases without evidence of product purchase? Q15 What is happening with the victim issue? Q16 How does it compare with the cases of Minamata disease and Wonjin Rayon? Q17 Are there prevention measures and lessons?

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.547-557
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• 1996

Background : An excessive accumulation of neutrophils in lung tissue has been known to play an important role in mediating the tissue injury among the adult respiratory distress syndrome, idiopathic pulmonary fibrosis and cystic fibrosis by releasing toxic oxygen radicals and proteolytic enzymes. Therefore, it is important to understand a possible mechanism of neutrophil accumulation in lung tissue. In many species, exposure to hyperoxic stimuli can cause changes of lung tissues very similar to human adult respiratory distress syndrome and neutrophils are also functioning as the main effector cells in hyperoxic lung injury. The purpose of the present study was to examine whether neutrophils function as a key effector cell and to study the nature of possible neutrophil chemotactic factors found in bronchoalveolar lavage fluid from the hyperoxia exposed rats. Methods : We exposed the rats to the more than 95% oxygen for 24, 48, 60 arid 72 hours and bronchoalveolar lavage(BAL) was performed. Neutrophil chemotactic activity was measured from the BAT- fluid of each experimental groups. We also evaluated the molecular weight of neutrophil chemotactic tractors using fast performance liquid chromatography and characterized the substances by dialyzer membrane and heat treatment. Results : 1) The neutrophil proportions in bronchoalveolar lavage fluid began to rise from 48 hours after oxygen exposure, and continued to be significantly increased with exposure times. 2) chemotactic index for neutrophils in lung lavages from rats exposed to hyperoxia was significantly higher in 48 hours group than in control group, and was significantly increased with exposure time. 3) No deaths occured until after 48 hours of exposure. However, mortality rates were increased to 33.3 % in 60 hours group and 81.3 % in 72 fours group. 4) Gel filtration using fast performance liquid chromatography disclosed two peaks of neutrophil chemotactic activity in molecular weight of 104,000 and 12,000 daltons. 5) Chemotactic indices of bronchoalveolar lavage fluid were significantly deceased when bronchoalveolar lavage fluid was treated with heat ($56^{\circ}C$ for 30 min or $100^{\circ}C$ for 10 min) or dialyzed (dialyzer membrane molecular weight cut off : 12,000 daltons). Conclusion : These results suggested that the generation of neutrophil chemotactic factor and subsequent neutrophil influx into the lungs are playing an important roles in hyperoxia-induced acute lung injury. Neutrophil chemotactic factor in the lung lavage fluids consisted of several distinct components having different molecular weight and different physical characteristics.

• Tuberculosis and Respiratory Diseases
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• v.61 no.4
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• pp.366-373
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• 2006

Background: Paraquat is extremely toxic chemical material, which generates reactive oxygen species (ROS), causing multiple organ failure. In particular, paraquat leads to irreversible progressive pulmonary fibrosis. Exaggerated cell deaths exceeding the normal repair of type II pneumocytes leads to mesenchymal cells proliferation and fibrosis. This study examined the followings; i) whether or not paraquat induces cell death in lung epithelial cells; ii) whether or not paraquat-induced cell deaths are apoptosis or necrosis; and iii) the effects of N-acetylcysteine, dexamethasone, and bcl-2 on paraquat-induced cell deaths. Methods: A549 and BEAS-2B lung epithelial cell lines were used. The cell viability and apoptosis were evalluated using a MTT assay, Annexin V staining was monitored by fluorescence microscopy, The level of bcl-2 inhibition was examined by establishing stable A549 pcDNA3-bcl-2 cell lines throung the transfection of pcDNA3-bcl-2 with the mock. Results: Paraquat decreased the cell viability in A549 and BEAS-2B cells in a dose and time dependent manner. The Annexin V assay showed that apoptosis was the type of paraquat-induced cell death. Paraquat-induced cell deaths was significantly inhibited by N-acetylcysteine, dexamethasone, and bcl-2 overexpression. The cell viability of A549 cells treated with N-acetylcysteine, and dexamethasone on the paraquat-induced cell deaths were increased significantly by 10 ~ 20%, particularly at high doses. In addition, the cell viability of A549 pcDNA3-bcl-2 cells overexpressing bcl-2 was significantly higher than the untransfected A549 cells. Conclusion: Paraquat induces apoptotic cell deaths in lung epithelial cells in a dose and time dependent manner. The paraquat-induced apoptosis of lung epithelial cells might occur through the mitochondrial pathway.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.241-250
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• 2002

Background : Coal-worker's pneumoconiosis(CWP) is characterized by a chronic inflammatory lung reaction associated with macrophage accumulation in the alveolar spaces. CWP is usually divided into two stage : simple pneumoconiosis(SP) where there are a limited number of fibrotic lesions remain limited, with radiological opacities smaller than 1cm and progressive massive fibrosis(PMF), which is characterized by the development of a perifocal extensive fibrotic response of the lung and severe alterations in pulmonary function. In this study, the lymphocyte compartment and cytokine were evaluated by measuring the serum levels in the control, SP and PMF groups. Materials and Methods : The coal workers selected for this study were employees(patients?) of the Tae-Baek and Dong-Hae hospital. All were men, 45-76 years old and the mean duration of their exposure to coal dust was 23.2 years in the lymphocyte compartment and 24.3 years in the cytokine checked group. According to X-ray examination results, the patients were classified into either one of the SP, PMF categories. The normal controls examined were 26-70 years old men. The serum cytokine levels were estimated by using an end point enzyme immunoassay technique. Results : T lymphocyte, helper and suppressor T cells were highly related to pneumoconiosis in this study. A statistically significant decrease in the number of suppressor T lymphocytes was observed in the simple pneumoconiosis patients and at the same time, there was an increase in the lymphocyte index. Howevere, there was no statistically difference in the serum cytokines levels among the SP, PMF and control groups. Conclusion : T lymphocyte, helper T, and suppressor T cells may be highly related to the development of CWP compared to the control group particularly in the early stage of pneumoconiosis. The changes observed in the immunological system in patients with pneumoconiosis may lie at the bottom of the pathogenesis of fibrosis. Further study is needed to evaluate the lymphocyte compartment as a marker for pneumoconiosis development in the early stage.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.338-345
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• 2002

Background : Coal workers' pneumoconiosis(CWP) is a fibrotic lung disease resulting from the chronic inhalation of coal dust. Various cytokines and growth factors secreted from macrophages and monocytes play a key role in the pathogenesis of pneumoconiosis. The platelet-derived growth factor (PDGF)-BB and the insulin-like growth factor(IGF)-1 secreated from the macrophages and monocytes are believed to stimulate the accumulation of mesenchymal cells and fibrosis of the lower respiratory tract that is observed in fibrotic lung disease. The serum concentraion of PDGF-BB and IGF-1 in 30 CWP patients and 10 healthy controls were measured in order to determine if PDGF-BB and IGF-1 can be used as sensitive biomarkers in CWP. Method : Serum was collected from 30 patients with CWP(13 with simple CWP and 17 with complicated CWP) and 10 healthy controls. The serum concentrations of PDGF-BB and IGF-1 were measured using ELISA (R&D system, Minneapolis, MN). Results : The serum PDGF-BB concentration in patients with complicated CWP($10083.76{\pm}639.07pg/mL$) was significantly higher than in the patients with simple CWP ($8493.88{\pm}848.51pg/mL$) and the healthy controls ($3726.17{\pm}292.20pg/mL$) (p<0.05). Compared to the healthy controls ($413.40{\pm}1.94ng/mL$), there was no significant difference in the serum IGF-1 concentration in patients with simple ($366.77{\pm}183.67ng/mL$) and complicated CWP ($403.18{\pm}15.39ng/mL$) (p>0.05). Conclusion : These results show the important role of the PDGF-BB mediated pathways in the pathogenesis of CWP. These data suggests that the PDGF-BB serum concentration is a useful biomarkers of the fibrotic extent in CWP patients.

• Clinical and Experimental Pediatrics
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• v.48 no.3
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• pp.327-332
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• 2005

Interstitial lung disease refers to a group of pulmonary disorders characterized by inflammation of the interstitium, derangements and loss of alveolar capillary units leading to disruption of alveolar gas exchange, which induces symptoms of restrictive lung disease. Cases of interstitial pneumonia in children are uncommon and mostly have unknown causes. We have experienced an 8-year old boy who had symptoms of cyanosis, dry cough, dyspnea and abrupt weight loss. He had not been exposed to organic dusts, allergens or any other systemic disease infections. Chest radiology showed diffuse ground glass opacity in both lung fields. High resolution computed tomography(HRCT) showed multiple small patchy areas of consolidation with an underlying ground glass appearance in both lungs. The pathologic findings of lung biopsy tissue showed patchy areas of interstitial fibrosis, alveolar obliteration and nodular fibrotic areas, strongly suggesting interstitial pneumonia. No specific finding of viral inclusion or any other evidence of infection was found under electromicroscopy. We used peak flow meters to compare functional improvement. Forced expiratory volume in one second ($FEV_1$) was decreased to 25 percent of predicted value. The boy was given treatment with prednisone and showed improvements in HRCT findings after two months. He was able to tolerate easy exercise in school and showed clinical improvements after one year of follow up.

• Radiation Oncology Journal
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• v.33 no.2
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• pp.89-97
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• 2015

Purpose: To evaluate the treatment results in early stage non-small cell lung cancer patients who have undergone fiducial-less CyberKnife radiosurgery (CKRS). Materials and Methods: From June 2011 to November 2013, 58 patients underwent CKRS at Asan Medical Center for stage I lung cancer. After excluding 14 patients, we retrospectively reviewed the records of the remaining 44 patients. All analyses were performed using SPSS ver. 21. Results: The median age at diagnosis was 75 years. Most patients had inoperable primary lung cancer with a poor pulmonary function test with comorbidity or old age. The clinical stage was IA in 30 patients (68.2%), IB in 14 (31.8%). The mean tumor size was 2.6 cm (range, 1.2 to 4.8 cm), and the tumor was smaller than 2 cm in 12 patients (27.3%). The radiation dose given was 48-60 Gy in 3-4 fractions. In a median follow-up of 23.1 months, local recurrence occurred in three patients (2-year local recurrence-free survival rate, 90.4%) and distant metastasis occurred in 13 patients. All patients tolerated the radiosurgery well, only two patients developing grade 3 dyspnea. The most common complications were radiation-induced fibrosis and pneumonitis. Eight patients died due to cancer progression. Conclusion: The results showed that fiducial-less CKRS shows comparable local tumor control and survival rates to those of LINAC-based SABR or CKRS with a fiducial marker. Thus, fiducial-less CKRS using Xsight lung tracking system can be effectively and safely performed for patients with medically inoperable stage I non-small cell lung cancer without any risk of procedure-related complication.