• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.217-224
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• 2000

Background : It is well known that when macrophages are stimulated with endotoxin, they produce a wide variety of cytokine mediators, including TNF-$\alpha$ and IL-1$\beta$. However, there is an alteration in the macrophages' responsiveness when they are challenged with repeated bouts of endotoxin, termed "endotoxin tolerance" which is regarded as a self-protective phenomenon from continuous stimulation. In this study, endotoxin tolerance in the peripheral blood monocytes of sepsis patients was evaluated. Methods : Fourteen patients with organism-documented sepsis were included. The severity of illness was evaluated by APACHE II score. Peripheral blood monocytes were isolated from the patients and diluted to $1{\times}10^5$ well. After stimulation with endotoxin (LPS of E. coli O114 : B4, 100 ng/ml), they were incubated at $37^{\circ}C$ in 5% $CO_2$ incubator for 24 hours. Supernatant was collected for the measurement of TNF-$\alpha$ and IL-1$\beta$ with ELISA method. Peripheral blood monocytes of seven healthy volunteers were used as control. Results : The APACHE II score (mean$\pm$SD) of the patients at the time of blood sampling was 12.2$\pm$5.7. The primary infection foci were urinary tract infection, pneumonia, subacute bacterial endocarditis, and catheter related infection, etc. The causative organisms were gram negative rods (10 cases), gram positive cocci (6 cases) with two cases of mixed infection. Serum TNF-$\alpha$ could be measured in 4 cases with 29.9$\pm$27.7 pg/ml. Serum IL-1$\beta$was measurable in only one patient. The TNF-$\alpha$ level of supernatant of cultured peripheral blood monocytes was 2,703$\pm$2,066 pg/ml in patients and 2,102$\pm$1914 pg/ml in controls. The IL-1$\beta$level of supernatant was 884$\pm$1,050 pg/ml in patients and 575$\pm$558 pg/ml in controls. There was no difference of TNF-$\alpha$ and IL-1$\beta$ level between patients and controls. Conclusion : We cannot prove the phenomenon of endotoxin tolerance in this study. Future study needs to be focused on the more severe sepsis patients who were taken for sampling earlier. Addition of serum to the culture medium could be an another valuable option for the success of this study.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.251-263
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• 1997

Background : The emergence of multidrug-resistant strains of Mycobacterium tuberculosis presents a significant challange to the treatment and control of tuberculosis, and there is an urgent need to understand the mechanisms by which strains acquire multidrug resistance. Recent advances in molecular methods for the detection of M. tuberculosis genetic targets have approached the sensitivity of culture. Furthermore the prospect of determining resistance in mycobacteria at the nucleic acid level particulary to first-line drugs like rifampin, isoniazid has provided a glimps of the next generation of sensitivity test for M. tuberculosis. Previous studies in RMP resistant M. tuberculosis have shown that mutation in $\beta$subunit of RNA polymerase is main mechanism of resistance. Method : In this study, rpoB gene for the $\beta$subunit of RNA polymerase from M. tuberculosis of 42 cultured samples (32 were RMP resistant and 10 were sensitive cases) were isolated and characterised the mutations. Direct sequencing data were compared with the results of INNO-LiPA Line Probe Assay (LiPA, Innogenetics, Belgium), commercial RMP resistance detecting kit using reverse hybridization method. Results : All of the RMP resistant samples were revealed the presence of mutation by LiPA. In 22 samples (68.8%) out of 32 RMP resistant cases, the mutation types were confirmed by the positive signal at one of 4 mutation bands in the strip. The most frequent type was R5 (S531L) which were 17 cases (77.3%). Results of direct sequencing were identified the exact characteristics of 8 mutations which were not confirmed by LiPA. S522W type point mutation and 9 base pair deletion at codon 513~515 were new identified mutations for the first time. Conclusion : Mutations in rpoB gene is the main mechanism of RMP resistance in M. tuberculosis and LiPA is a very useful diagnostic tool for the early diagnosis of RMP resistance in M. tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1167-1177
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• 1998

Background : Pulmonary tuberculosis is one of the diseases characterized granuloma formation which was controlled by cellular immune reactions. In the process of granulomatous changes, activated alveolar macrophages and T lymphocytes secrete many cytokines including interleukin-1 (IL-1), tumor necrosis factor-alpha(TNF-$\alpha$), interferon-gamma(IFN-$\gamma$) which mediate inflammatory reactions. Intercelluar adhesion molecule-1(ICAM-1) also known to major role player in inflammatory processes, and increased cellular expressions when endothelial cell was stimulated by IL-1, TNF and IFN. Method : To evaluate relationships among cellular immune reactions and clinical stages, pulmonary tuberculosis patients were classified into three groups according to their clinical stages including minimal, moderate and far advanced tuberculosis. TNF-$\alpha$ IFN-$\gamma$, sICAM-1 (soluble form of ICAM-1) were measured at the time of diagnosis and after 6-months anti-tuberculosis medications by radioimmuno assay or enzyme linked immunosolvent assay. Result : TNF-$\alpha$, IFN-$\gamma$, sICAM-1 were significantly increased in moderate and far advanced pulmonary tuberculosis patients but no meaningful changes in minimal staged patients. 6-months anti-tuberculosis medications reduced serum sICAM-1 levels significantly, related to clinical improvement but no significant changes were found in the serum levels of TNF-$\alpha$ and IFN-$\gamma$. In the point of correlations. positive ones revealed between TNF-$\alpha$ and sICAM-1, also between IFN-$\gamma$ and sICAM-1 but no correlation between TNF-$\alpha$ and IFN-$\gamma$. Conclusion : Measurement of serum sICAM-1 could be useful parameter to evaluate the severity of pulmonary tuberculosis and to monitor disease activities during anti-tuberculosis medications.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.837-852
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• 2000

Backgrounds : Today, tuberculosis cannot only be cured medically, but also controlled by public health. Despite the overall worldwide decline in tuberculosis, the disease continues to be a significant problem among developing countries and in the slums of large cities in some industrialized countries. Particularly, this communicable disease has come into the public health spotlight because of its resurgence in the 1990's. our country has been operating the Korean National Tuberculosis Control Program since 1962, focusing around public health centers. Therefore, this study aims to compare the effectiveness of tuberculosis control activities, one of the major public health activities in Korea, by producing indexes, such as the yearly registration rate per 100,000 population and treatment compliance of tuberculosis on in small areas (communities). Methods : This work was accomplished by constructing a time-series analytic model using data from "1980~2000: the Yearly Statistical Report" with patient registry data of 234 City. County. District public health centers and by identifying the factors influencing the tuberculosis indexes. Results : The trends of pulmonary tuberculosis positive point prevalence and pulmonary tuberculosis negative point prevalence on X-ray screening have declined steadily, beginning in 1981 and continuing to 1998 by region (city, county, district). Although the tuberculosis mortality rate steadily shows a declining trend by year and region, but Korea still ranks first among 29 OECD countries in 1998, with a tuberculosis mortality rate of 7.1 per 100,000 persons, according to the time-series analysis for fatal diseases. Conclusion : The results of the study will form the fundamental basis of future regional health care planning and the Korean Tuberculosis Surveillance System on 2000. Since the implementation of local autonomy through the Local Health Act of 1995, it has now become vita1 for each city, county, district public health centers to determine its own priorities for relevant health care management, including budget allocation and program goals.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.540-548
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• 2001

Backgrounds : Because ventilator-induced lung injury is partly dependent on the intensity of vascular flow, we hypothesized that hypothermia may attenuate the degree of such an injury through a reduced cardiac output. Methods : Twenty-seven male Sprague-Dawley rats were randomly assigned to normothermia ($37{\pm}1^{\circ}C$)-injurious ventilation (NT-V) group (n=10), hypothermia ($27{\pm}1^{\circ}C$)-injurious ventilation (HT-V) group (n=10), or nonventilated control group (n=7). The two thermal groups were subjected to injurious mechanical ventilation for 20 min with peak airway pressure 30 cm $H_2O$ at zero positive end-expiratory pressure, which was translated to tidal volume $54{\pm}6\;ml$ in the NT-V group and $53{\pm}4\;ml$ in the HT-V group (p>0.05). Results : Pressure-volume (P-V) curve after the injurious ventilation was almost identical to the baseline P-V curve in the HT-V group, whereas it was shifted rightward in the NT-V group. On gross inspection, the lungs of the HT-V group appeared smaller in size, and showed less hemorrhage especially at the dependent regions, than the lungs of the NT-V group. [Wet lung weight (g)/body weight (kg)] ($1.6{\pm}0.1$ vs $2.4{\pm}1.2$ ; p=0.014) and [wet lung weight/dry lung weight] ($5.0{\pm}0.1$ vs $6.1{\pm}0.8$ ; p=0.046) of the HT-V group were both lower than those of the NT-V group, while not different from those of the control group($1.4{\pm}0.4$, $4.8{\pm}0.4$, respectively). Protein concentration of the BAL fluid of the HT-V group was lower than that of the NT-V group($1,374{\pm}726\;ug/ml$ vs $3,471{\pm}1,985\;ug/ml$;p=0.003). Lactic dehydrogenase level of the BAL fluid of the HT-V group was lower than that of the NT-V group ($0.18{\pm}0.10\;unit/ml$ vs $0.43{\pm}0.22\;unit/ml$;p=0.046). Conclusions : Hypothermia attenuated pulmonary hemorrhage, permeability pulmonary edema, and alveolar cellular injuries associated with injurious mechanical ventilation, and preserved normal P-V characteristics of the lung in rats.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.797-806
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• 1999

Background: About 20% of small cell lung cancer(SCLC) patients have bone marrow(EM) metastasis at the time of diagnosis and the remaining patients are also considered with micrometastasis. In an attempt to detect EM micrometastasis, we used cytokeratin(CK)-20 as a molecular marker, which is specific for epithelial cells. Method: A sensitive RT-PCR assay was used to compare CK-20 expression both in SCLC cell line H209 and normal leukocyte and to evaluate EM aspirates of 28 SCLC patients. Result: H209 cell line showed CK-20 expression but normal leukocyte did not, suggesting CK-20 expression is lung tissue-specific. Of 28 patients(11 limited disease, 17 extensive disease), only 2(1/11, 1/17) samples tested revealed positive signal for CK-20. Two patients with CK-20 expression had EM metastasis or multiple bone involvement during follow-up. Conclusion: Although circulating tumor cells were detected in EM of small portion of patients with bone metastasis, CK-20 doesn't seem to be a reliable marker for the detection of micrometastasis in SCLC. This study emphasizes that identification of more specific marker for micrometastsis is mandatory prior to clinical application.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.207-216
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• 2000

Background : The occurrence of lung complications after allogenic bone marrow transplantation(BMT) has been reported as 40-60 percent. The risk factors for lung complications are whole body irradiation, high dose chemotherapy, graft versus host disease, old age and CMV infection. The prevalence of graft versus host disease is less in Korea than in Western countries, but frequency of CMV infection is higher. Therefore, the pattern of lung complications may be different in Korea from those in Western countries. Methods : A retrospective cohort study was performed on one hundred consecutive adult patients who underwent allogenic bone marrow transplantation from December, 1993 to May, 1999 at Asan Medical Center. Lung complications were divided into two groups by the time of development, within 30days (pre-engraftment) and beyond 30 days (post-engraftment), and then subdivided into infectious and non-infectious complication. Infectious complications were defined as having the organism in blood, BAL fluid, pleural fluid or sputum, or compatible clinical findings in patients, which improved with antibiotics or an anti-fungal therapy. Result: 1) Eighty three episodes of lung complications had occurred in 54 patients. 2) Within thirty days after BMT, non-infectious complications were more common than infections, but this pattern was reversed after 30 days. After one year post-BMT, there was no infectious complication except in cases of recurrence of underlying disease or development of chronic GVHD. 3) Among the non-infectious complications, pleural effusion (27 episodes) was most common, followed by pulmonary edema (8 episodes), bronchiolitis obliterans(2 episodes), diffuse alveolar hemorrhage (1 episode) and bronchiloitis obliterans with organizing pneumonia (1 episode). 4) The infectious complications were pneumonia (bacterial: 9 episodes, viral: 4 episodes, fungal : 5 episodes, pneumocystis carinii : 1 episode), pulmonary tuberculosis(3 episodes) and tuberculous pleurisy (3 episodes). 5) Lung complications were more frequent in CMV positive patients and in patients with delayed recovery of neutrophil count. 6) The mortality was higher in the patients with lung complications. Conclusion : Lung complications developed in 54% after allogenic BMT and were associated with higher mortality.

• Tuberculosis and Respiratory Diseases
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• v.56 no.4
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• pp.364-373
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• 2004

Background : Obstructive sleep apnea is a contributory factor of hypertension, arrhythmia, ischemic heart disease and other cardiovascular diseases. However, the pathophysiology underlying this relationship is unclear. Recent reports have shown that the soluble intercellular adhesion molecule-1(sICAM-1) and vascular endothelial growth factor(VEGF) are involved in the initiation and progression of atherosclerosis, and some reports state that increased levels of these cytokines are found in patients with obstructive sleep apnea. In this study, the levels of sICAM-1 and VEGF were measured in patients with obstructive sleep apnea in order to determine if obstructive sleep apnea is involved in the pathophysiology of cardiovascular diseases. Methods : Thirty-seven patients were chosen amongst a population who visited the Sleep Disorders Clinic of St. Paul's Hospital in Seoul, Korea for a diagnosis of obstructive sleep apnea and who had subsequently undergone an overnight polysomnography at the clinic. The sera from these patients were retrieved after an overnight polysomnography session and the samples were kept at $-70^{\circ}C$. The cytokine levels were determined with ELISA and the relationships between the serum levels of sICAM-1 and VEGF along with polysomnography parameters were analyzed. Results : No statistically significant correlation was observed between the sICAM-1 levels and the apnea-hypopnea index(r=0.27, P>0.05). Positive correlations were found between the apnea-hypopnea index and serum VEGF levels (r=0.50, P<0.01), the apnea index and the serum sICAM-1 levels (r=0.31, P<0.01), and the apnea index and the serum VEGF levels (r=0.45, P<0.01). Conclusions : Obstructive apnea or hypopnea leads to an increase in the sICAM-1 and VEGF levels. Such an increase in the cytokine levels most likely leads to the higher incidence of cardiovascular diseases observed in patients with obstructive sleep apnea.

• Tuberculosis and Respiratory Diseases
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• v.64 no.3
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• pp.200-205
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• 2008

Background: Tumor angiogenesis plays an important role in tumor growth, maintenance and metastatic potential. Tumor tissue produces many types of angiogenic growth factors. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumor angiogenesis. In this study, the expression of tissue VEGF and bFGF from non-small cell lung cancer (NSCLC) patients were analyzed. Methods: We retrospectively investigated 35 patients with a histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, where the primary curative approach was surgery. An ELISA was employed to determine the expression of VEGF and bFGF in extracts prepared from 35 frozen tissue samples taken from the cancer patients. Results: VEGF and bFGF concentrations were significantly increased in lung cancer tissue as compared with control (non-cancerous) tissue. The VEGF concentration was significantly increased in T2 and T3 cancers as compared with T1 cancer. Expression of VEGF was increased in node-positive lung cancer tissue as compared with node-negative lung cancer tissue (p=0.06). VEGF and bFGF expression were not directly related to the stage of lung cancer and patient survival. Conclusion: Expression of VEGF and bFGF were increased in lung cancer tissue, and the expression of VEGF concentration in lung cancer tissue was more likely related with tumor size and the presence of a lymph node metastasis than the expression of bFGF. However, in this study, expression of both VEGF and bFGF in tissue were not associated with patient prognosis.

• Journal of Korean Society of Forest Science
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• v.95 no.6
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• pp.649-656
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• 2006

The purpose of study is to measure soil erosion quantity for elapsed four years from the fire on forest fired sites of Dong-gu, Daegu. This study was conducted to investigate the characteristics of soil erosion by fire occurrence influencing on the soil erosion were. Also analysis result follows that the relations between soil erosion quantity and rainfall intensity, the slope and elapsed year. The results analysed were as follows: 1. Soil erosion by year of occurrence of forest fire was increased 1.9 to 5.7 times as rainfall intensity was increased by 30 m/hr, and 1.4 to 14.2% as degree of slope was increased by $10^{\circ}$. 2. In the first year of forest fire occurrence, soil erosion was fairly heavy for 10 minutes of initial rainfall of which rainfall intensity was 80 m/hr and degree of slope was $30^{\circ}$. The amount of soil erosion was gradually reduced as elapsed time. From two years after fire, the amount of soil erosion by rainfall intensity and degree of slope was nearly constant. 3. The amount of soil erosion by rainfall intensity and slope in accordance with elapsed time after fire was reduced 28.9 to 94.1% in three years after occurrence of forest fire as compared to the first year of fire. Soil erosion was fairly heavy by rainfall intensity and slope in the first year of fire, but it was gradually reduced from two years after fire. 4. In the analysis on influences of each factors on the amount of soil erosion on forest fired sites, the amount of soil erosion was significant differences in major impacts of each rainfall intensity, degree of slope and elapsed year after fire and interaction of rainfall intensity${\times}$degree of slope and rainfall intensity${\times}$elapsed year after fire, but no differences were observed in interaction of degree of slope${\times}$elapsed year after fire and rainfall intensity${\times}$degree of slope${\times}$elapsed year after fire. Rainfall intensity was the most affecting factor on the amount of soil erosion and followed by degree of slope and elapsed year after fire. 5. For correlation between soil erosion and affecting three factors, soil erosion showed significant positive relation with rainfall intensity and degree of slope at I % level, and significant negative relation with elapsed year after fire at 1 % level. 6. As a result of regression of affecting three factors on soil erosion. rainfall intensity was most significant impact factor in explaining the amount of soil erosion on forest fired sites, followed by degree of slope and elapsed year after forest fire. 7. The formula for estimating soil erosion using rainfall intensity, degree of slope and elapsed year after forest fire occurrence was made. S.E = 0.092R.I + 0.211D.S - 0.942E.Y(S.E : Soil erosion, R.I : Rainfall intensity, D.S : Degree of slope, E.Y : Elapsed year after forest fire occurrence)