• Tuberculosis and Respiratory Diseases
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• v.64 no.5
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• pp.347-355
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• 2008

Background: IPF is characterized by chronic, fibrosing inflammatory lung disease of unknown etiology. Typical symptoms of IPF are exertional dyspnea with nonproductive cough. Why patients with typical IPF have dry cough rather than productive cough, is unknown. IP-10 plays an important regulatory role in leukocyte trafficking into the lung. The present study investigated the effect of IP-10 in the pathogenesis of dry cough rather than productive cough in IPF patients. Methods: IP-10 concentration was measured by ELISA from BALF of IPF patients. To evaluate the role of IP-10 in mucin expression, the expression of the MUC5AC mucin gene was measured in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation by TNF-${\alpha}$ with or without IP-10 pretreatment. EGFR-MAPK expression was also examined as a possible mechanism. Results: IP-10 levels were significantly higher in the BALF of IPF patients compared to healthy controls. IP-10 pretreatment reduced TNF-${\alpha}$ induced MUC5AC mucin expression by inhibiting the EGFR-MAPK signal transduction pathway in NCI-H292 cells. Conclusion: These findings suggest that little mucus production in IPF patients might be attributable to IP-10 overproduction, which inhibits the EGFR-MAPK signal transduction pathway required for MUC5AC mucin gene expression.

• Korean Journal of Agricultural Science
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• v.7 no.1
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• pp.52-58
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• 1980

This study was conducted to detect copper which is considered in the soils of orchards, since copper fungicide has been applied to fruit trees. Soil samples taken from the fields of the chief producing districts of apple (Chungju, Yesan, Daegu), pear (Yangju, Bucheon, Seonghwan) and citrus (Seogypo in Jeju island) were analysed by an atomic absorption spectrophotometer. The results obtained were summarized as follows ; 1. In orchards of apple, the amount of copper of soils from Yesan, Chungju and Daegu were ranged 2.6-171.3ppm, 2.2-136.1ppm and 14.3-134.6ppm, respectively. Very little copper was detected from the soils in the field which has been cultivated for less than 20 years. About 100ppm and 130-170ppm of copper were detected in the field which has been cultivated for 30 years and for 50-60 years, respectively. Most of the copper was detected in the surface layer of soils (0-10cm), while very low content of copper was detected in the deeper layer of soils (10-20cm). 2. In orchards of pear, 20-30ppm of copper was detected from the surface of soils in the field which has been cultivated for more than 30 years and the highest level of copper, 36.8ppm, was detected from Yangju area. The amount of copper of soils from Yangju, Seonghwan and Bucheon were ranged 3.6-36.8ppm, 9.7-19.4ppm and 3.6-24.7ppm, respectively. 3. In orchards of citrus of Jeju island, only trace amount and 23-38ppm of copper were detected in the fields cultivated for 15 years and 20-30 years, respectively. The highest level of copper, 57ppm, was detected from the surface layer of soils in the field which has been cultivated for 35 years, but in most of the soil samples tested, only the natural background level of copper, about 20ppm, was detected. 4. The levels of copper residue in all the soil samples tested were lower than the tolerance level (125ppm of copper which is extracted in 0.1N-HCl solution), except those of copperr residue, 130-170ppm, that were detected from the orchards of apple which have been under cultivation for 50-60 years. Hence no problem for the farming could be speculated with the present concentration of copper analysed.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.156-165
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• 2002

Background: A tracheal stenosis is caused by mucosal ischemic injury related to a high cuff pressure ($P_{cuff}$) of the endotracheal tube. In contrast, aspiration of the upper airway secretion and impaired gas exchange due to cuff leakage is related to a low $P_{cuff}$. To prevent these complications, the $P_{cuff}$ should be kept appropriately because the appropriate $P_{cuff}$ appears to change according to the patient's daily respiratory mechanics. However, the constant cuff volume($V_{cuff}$) has frequently been instilled to the cuff balloon on a daily basis to maintain the optimal $P_{cuff}$ instead of monitoring the $P_{cuff}$ directly at the patients' bedside. To address the necessity of continuous $P_{cuff}$ monitoring, the change in the $P_{cuff}$ was evaluated at various $V_{cuff}$ levels on a daily basis in patients with long-term mechanical ventilation. The utility of mercury column sphygmomanometer for the continuous monitoring $P_{cuff}$ was also investigated. Method: The change in $P_{cuff}$ according to the increase in $V_{cuff}$ was observed in 17 patients with prolonged endotracheal intubation for mechanical ventilation for 2 week or more. This maneuver measured the change in $P_{cuff}$ daily during the mechanical ventilation days. In addition, the $P_{cuff}$ measured by mercury column sphygmomanometer was compared with the $P_{cuff}$ measured by an automatic cuff pressure manager. Results : There were no statistically significant changes of $P_{cuff}$ during more than 14 days of intubation for mechanical ventilation. However the $V_{cuff}$ required to maintain the appropriate $P_{cuff}$ varied from 1.9 cc to 9.6 cc. In addition, the intra-individual variation of the $P_{cuff}$ was observed from 10 $cmH_2O$ to 46 $cmH_2O$ at constant 3 cc $V_{cuff}$. The $P_{cuff}$ measured by the bedside mercury column sphygmomanometer is well coincident with that measured by the automatic cuff pressure manager. Conclusion: Continuous monitoring and management of the $P_{cuff}$ to maintain the appropriate $P_{cuff}$ level in order to prevent cuff related problems during long-term mechanical ventilation is recommended. For this purpose, mercury column sphygmomanometer may replace the specific cuff pressure monitoring equipment.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.107-116
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• 2002

Background: Matrix metalloproteinases(MMP) are essential enzymes for tumor invasion and metastasis. Among the MMP family, elevated MMP-9 and stromelysin-3(STR-3) expression have been reported to be poor prognostic factors in lung cancer patients. To evaluate the possibility of a molecular diagnosis of lung cancer using peripheral blood, the mRNA expression level of MMP-9 and STR-3 was measured using a reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with lung cancer. Methods : Ninety six patients(44 patients with lung cancer, 19 pulmonary infection, and 33 control) were included. To detect MMP-9 and STR-3 mRNA expression, RT-PCR was performed in peripheral blood mononuclear cells. ELISA was also used to measure the serum level of MMP-9. Results : MMP-9 was expressed more frequently in patients with a pulmonary infection(18/19, 94.7%) compared to lung cancer patients(26/44, 59.1%) or the controls (23/33, 69.7%) (p=0.018). On the other hand, STR-3 expression was observed more frequently in patients with lung cancer(37/44, 84.1%) compared to the lung infection patients(8/19, 42.1%) or control(20/33, 60.6%) (p=0.003). Among the lung cancer patients, MMP-9 was expressed more frequently when a tumor invaded the lymph nodes(17/24, 70.8%) compared to when a tumor did not(3/13, 23.1%) (p=0.005). The MMP-9 and STR-3 expression levels had no relationship with age, sex, tumor size, distant metastasis, or tumor histology. The serum MMP-9 concentration was not higher in lung cancer patients compared to patients with a pulmonary infection or the control subjects. Conclusion : STR-3 may be used as a diagnostic marker in the peripheral blood of lung cancer patients using RT-PCR. Further studies to evaluate the clinical significance of elevated STR-3 expression in lung cancer patients is recommended.

• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.12-28
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• 2001

Background and Object : Immunostimulatory CpG-oligodeoxynucleotides (ISS CpG-ODN) up-regulate the $T_{H1}$-type immune response and down-regulate the $T_{H2}$-type response. This study was performed to investigate the immune response changes resulting from ISS CpG-ODN on bronchial hyperresponsiveness, eosinophilic inflammation and mucus hypersecretion in rat asthma. Materials and Methods : 10 normal controls(NC) and 26 asthmatic rats, which were generated by ovalbumin(OVA) sensitization and challenge, were studied. The asthmatic rats were randomized into 11 asthma controls(AC) and 15 in the asthma-CpG treatment group(CpG). The CpG group was administered ISS CpG-ODN intramuscularly and the AC group was administered a placebo(0.9% NaCl) on day 15 and 20. After CpG-ODN or placebo administration, we measured the IFN-${\gamma}$($T_{H1}$-type cytokine) and IL-4($T_{H2}$-type cytokine) levels in the bronchoalveolar lavage fluid(BALF), the specific airway resistance(sRaw), eosinophilic fraction in BALF, eosinophilic infiltration, goblet cell dysplasia and MUC5AC gene expression in the lung tissue. Results : In the BALF of the CpG group, the IFN-${\gamma}$ concentration was significantly high and the IL-4 concentration was significantly low when compared with the AC group. Both the sRaw and eosinophilic fraction, and infiltration into the BALF and lung tissue significantly lower in the CpG group when compared with the AC group. However, little difference in goblet cell dysplasia and MUC5AC gene expression was observed between the CpG group and the AC group. Conclusion : ISS CpG-ODN decreases bronchial hyperresponsiveness and eosinophilic inflammation in the rat asthma model through the up-regulation of the $T_{H1}$-type immune response with the down-regulation of the $T_{H2}$-type response. However, the effect of these immune response changes on mucus hypersecretion was is not remarkable in this study.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.280-289
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• 1998

Background: It is sometimes difficult to differentiate tuberculous pleural effusion from malignant pleural effusion by clinical symptoms, signs, by routine tests of pleural fluid, and by pathologic studies. And recently, it was discovered that cytokines such as IL-2, IFN-$\gamma$, TNF-$\alpha$ are elevated in tuberculous pleural fluid, and there have been several attempts to diagnose tuberculous pleural effusion by using these immunological mediators. There are several studies regarding the diagnostic value of IFN-$\gamma$, and there are two studies in Korea. But the diagnostic values of IFN-$\gamma$ in these studies were slightly lower than those in other countries. To compare the diagnostic value of IFN-$\gamma$ with those of CEA and ADA, and to determine the sensitivity and specificity of IFN-$\gamma$ in Korean, we mesured IFN-$\gamma$, CEA level and ADA activity in pleural effusions. Methods: ADA activity, IFN-$\gamma$ level and CEA level as well as cell count, differential count, and biochemical assays such as protein content and lactate dehydrogenase were measured in 40 cases of tuberculous pleuritis and 42 cases of malignant pleural effusion. Results: Tuberculous pleural fluid showed higher levels of IFN-$\gamma$ and ADA ($832.6{\pm}357.2$ pg/ml and $82.5{\pm}25.9$ U/L, respectively) than those of malignant pleural effusion ($2.6{\pm}8.0$ pg/ml and $19.2{\pm}10.9$ U/L, respectively) (p<0.01). Malignant pleural effusions showed higher median value (102.2 ng/ml) than tubercalous pleural effusions (1.8 ng/ml) (p<0.01). The sensitivities of IFN-$\gamma$, ADA, CEA were 0.97, 0.87, 0.67 and the specificities of IFN-$\gamma$, ADA, CEA were 1.0, 0.97, 1.0, respectively. There was no significant correlation between ADA activity and IFN-$\gamma$ level. Conclusion: This study showed that IFN-$\gamma$ test would be a very useful clinical test for differential diagnosis of tuberculous pleuritis and malignant pleural effusion because it is very sensitive and specific, although it is an expensive test.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.1031-1038
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• 1998

Background: Most of malignant pleural effusions are serous but 8-33% of them are bloody. We wanted to evaluate the relationships between gross appearance and pleural CEA level or results of histocytology in malignancy associated pleural effusions. We also tried to reevaluate the meaning of CEA measurement in histocytologically proved or unproved malignancy associated pleural effusions. Methods: We studied 98 cases of malignancy associated pleural effusions, 50 cases of histocytologically proven malignant effusions and 48 cases of histocytologically unproven paramalignant effusions. We had observed gross appearance and conventional laboratory values and CEA levels for pleural effusions. Results: 44.9% of malignancy associated effusions were bloody(63.6% of bloody effusions were histocytologically proven malignant effusion). 65.0% of malignancy associated pleural effusions which have RBCs numbers over $100,000/mm^3$ were cytologically proven malignant effusions. 72.7% of cytologically proven malignant effusions had increased pleural fluid CEA level over 10 ng/ml. 58.2% of cases with pleural CEA over 10 ng/ml had positive results in pleural bistocytology. There was no definable relationships between pleural fluid CEA elevation and RBCs numbers and results of pleural fluid cytology. Conclusion: About half of the cases with malignancy associated pleural effusions were bloody. Histocytologically proven malignant effusions were more common in bloody effusion than non-bloody effusion(63.6% Vs 38.9%). But increased red blood cell numbers was not associated with positivity of pleural histocytology. Pleural fluid CEA elevation(over 10 ng/ml) was not correlated with positive pleural histocytology. But pleural fluid CEA elevation was rare in nonmalignant pleural effusions, and than pleural CEA measurement in uncertain pleural effusions maybe helpful to distinguishes its origin.

• Tuberculosis and Respiratory Diseases
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• v.58 no.4
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• pp.359-366
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• 2005

Background : IGFBP-3 inhibits the mitogenic and anti-apoptotic activity of IGF by blocking the binding of IGF to its receptor. However, under certain circumstances, IGFBP-3 can enhance the activity of IGF by protecting IGF from its degradation. More than half of the interindividual variations in IGFBP-3 levels are known to be genetically determined by the polymorphism at -202 locus of IGFBP-3 gene. Method : We attempted to ascertain whether A-202C polymorphic variation of IGFBP-3 gene constitutes a risk factor for non-small cell lung cancer (NSCLC), using PCR-restriction fragment length polymorphism (RFLP). Our study included 104 NSCLC patients and 104 age-, gender-, and smoking status-matched control subjects. Result : In the 104 NSCLC subjects, the genotypic frequencies at the -202 site were as follows: AA = 67 (64.4%), AC = 35 (33.7%), and CC = 2 (1.9%). We did detect significant differences in the genotypic distribution between the NSCLC and the control subjects (p<0.05), and the NSCLC risk correlated significantly with AA genotype at the -202 locus (AA>AC>CC). Using CC genotype as a reference, the odds ratio (OR) for the subjects with AC genotype was 2.60 (95% CI: 0.89 - 8.60), and the OR associated with AA genotype was 5.89 (95% CI: 1.92 - 21.16). Conclusion : These results indicate that the dysregulation of IGF axis should now be considered as another important risk factor for NSCLC, and a potential target for novel antineoplastic therapies and/or preventative strategies in high-risk groups.

• Tuberculosis and Respiratory Diseases
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• v.61 no.1
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• pp.20-25
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• 2006

Background: Although fever is one of the most common and challenging problem in intensive care medicine(ICU), it is difficult to distinguish between infectious and non-infectious causes. Procalcitonin(PCT) has recently been reported to be an indicator of various infectious diseases. This study examined whether or not measuring the serum PCT level in patients with fever in the ICU can help distinguish fevers with infectious causes from those with non-infectious causes. Methods: ICU patients with fever at $38^{\circ}C$ or over from March to August 2005 were prospectively enrolled. The cause of the fever was identified by the culture results and clinical course. The leukocytes, CRP, PCT, IL-6, and $TNF-{\alpha}$ in the fever patients with infectious and non-infectious causes were compared, and the PCT level in the patients with fever in the ICU were compared with those without fever. Results: 1) 42 patients were enrolled and 46 cases of fever were analyzed. 26 cases were considered to be infectious, while 13 cases were considered to be non-infectious. 7 cases were found to have no clear causes. 2) There were no significant differences in the degree of fever, leukocytes count, CRP, IL-6, and $TNF-{\alpha}$ levels in the patiemts with infectious and non-infectious causes. 3) The serum PCT level was higher in those with infectious causes than in those with non-infectious causes ($15.1{\pm}32.57ng/mL$ vs $2.68{\pm}3.63ng/mL$) but there was no statistical significance (p=0.06). 4) The serum PCT level of the ICU patients with fever was significantly higher than in those without fever ($10.94{\pm}27.15ng/mL$ vs $0.45{\pm}0.49ng/mL$) (p=0.02). Conclusion: The serum PCT cannot be used to distinguish the fever in ICU patients with infectious causes from that with non-infectious causes.

• Tuberculosis and Respiratory Diseases
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• v.60 no.6
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• pp.663-672
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• 2006

Background: $PM_{10}$(Particulate matter with a diameter ($<10{\mu}m$), which is characterized by different environmental conditions, is a complex mixture of organic and inorganic compounds. The Asian dust event caused by meteorological phenomena can also produce unique particulate matter in affected areas. This study investigated the cytokine produced by A549 epithelial cells exposed to particles collected during both the Asian dust pfenomenon and ambient air particles in a non-dusty period. Method: Air samples were collected using a high volume air sampler(Sibata Model HV500F) with an air flow at $500{\ell}/min$ for at least 6 hours. The cytokine messenger RNA(mRNA) was measured using a reverse transcriptase polymerase chain reaction(RT-PCR). The A549 cells were exposed to 10 to $500{\mu}g/m{\ell}$ of a suspension containing $PM_{10}$ for 24 hours. Each was compared with those in the non-exposed control cells. Result: The mRNA levels of interleukin(IL)-$1{\alpha}$, $IL-I{\beta}$, IL-8, and the granulocyte macrophage colony stimulating factor(GM-CSF) increased after veing exposed to $PM_{10}$ in the ambient air particles, compared with those in the non-exposed control cells. The increase in $IL-1{\alpha}$ and IL-8 were dose dependent at a $PM_{10}$ concentration between $100{\mu}g/m{\ell}$ and $500{\mu}g/m{\ell}$. The mRNA level of IL-8 in the A549 epithelial cells was higher during the in the Asian dust period($500{\mu}g/m{\ell}$) than during the non dust period. Conclusion: A549 cells exposed to the $PM_{10}$ collected during the Asian dust period produce more proinflammatory cytokine than during non-dusty period. This cytokine enhances the local inflammatory response in the airways and can also contribute to the systemic component of this inflammatory process.