• Radiation Oncology Journal
• /
• v.19 no.2
• /
• pp.181-189
• /
• 2001

Purpose : Changes in the balance between MMP and TIMP can have a profound effect on the composition in the extracellular matrix (ECM) and affect various cellular functions including adhesion, migration, differentiation of cells, and fibrosis and invasion and metastasis of cancer cells. Radiation therapy is a popular treatment modality for benign and malignant tumor, but the study for radiation effect on MMP and TIMP is scarce. In the current study, we have examined the expression of TIMP in fibrosis-prone (C57BL/6) mice after radiation. Methods and Materials : Adult female mice of $10\~12$ weeks were used. The whole body were irradiated using a Varian CL-4/100 with 2 and 10 Gy. Immunohistochemical staining was peformed according to Avidin Biotin complex method and evaluated by observing high power field. For TIMP-1, TIMP-2 antibodies, reactivity was assessed in the parenchymal cell and in the stromal cell. The scale of staining was assessed by combining the quantitative and qualiative intensity of staining. Results : TIMP-1 immunoreactivity did not change in lung. But, in liver, TIMP-1 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell. in kidney, TIMP-1 immunoreactivity was localized in cytoplasm of some tubular cell. Temporal variations were not seen. Dose-response relationship was not seen except kidney. TIMP-2 immunoreactivity in lung was a score (++) at 0 Gy and elevated to a score (+++) at 2 Gy. TIMP-2 immunoreactivity was a score (++) in liver at 0 Gy. TIMP-2 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell as same as patterns of TIMP-1 immunoreactivity. The TIMP-2 immunoreactivity in liver was elevated to (+++) at 2 Gy. Immunoreactivity to TIMP-2 in kidney was a score (+++) at 0 Gy and was not changed at 10 Gy. The score of TIMP-2 immunoreactivity was reduced to (++) at 2 Gy. TIMP-2 immunoreactivity was confined to tubules in kidney. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIMP-2 immunoreactivity was not seen. Conclusions : Differences between intensity of expression of TIMP-1 and TIMP-2 in each organ was present. Expression of TIMP was localized to specific cell in each organ. Irradiation increased TIMP-1 immunoreactivity in the liver and the kidney. Irradiation increased TIMP-2 immunoreactivity in the lung. But, in the liver and the kidney, TIMP-2 expression to radiation was irregular. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIHP-2 immunoreactivity was not seen. In the future, we expect that the study of immunohistochemical staining of longer period of postirradiation and quantitative analysis using western blotting and northern blotting could define the role of TIMP in the radiation induced tissue fibrosis.

• Tuberculosis and Respiratory Diseases
• /
• v.67 no.1
• /
• pp.14-20
• /
• 2009

Background: The pathophysiologic mechanisms of radiation-induced lung injury should be elucidated to enhance the therapeutic efficacy of radiotherapy and to manage patients exposed to serious radiation by accident. It has been suggested that pro-inflammatory cytokines play an important role in radiation-induced effect on the lung. This study was aimed to investigate changes in pro-inflammatory cytokines such as TNF-$\alpha$, MIP-2, IL-1$\beta$ and HMGB1, a newly recognized inflammatory mediator. Methods: The chests of BALB/c mice were selectively irradiated with single fraction of 20 Gy and then sacrificed at indicated times. Pathologic changes in the lung were examined after H&E staining. The expression level of pro-inflammatory cytokines was evaluated by ELISA kits in lung homogenate and in serum. Results: Radiation induced inflammatory changes and mild fibrosis in lung. Biphasic increase of TNF-$\alpha$ and IL-1$\beta$ was found in lung homogenate at 4 hours and at 3 weeks after radiation. The elevation in the second phase tended to be more intense. However, there was no similar change in serum. MIP-2 level was slightly increased in lung homogenate at 4 hours, but not at 3 weeks. HMGB1 was increased at 3 weeks in serum while there was no significant change in lung homogenate. Conclusion: Radiation induced a biphasic increase in TNF-$\alpha$ and IL-1$\beta$. The effective control of second phase cytokine elevation should contribute to preventing severe lung fibrosis caused by radiation.

• Tuberculosis and Respiratory Diseases
• /
• v.40 no.5
• /
• pp.565-574
• /
• 1993

Background: Pulmonary hamartomas are benign tumors that occur in the parenchyma or in the bronchi. They present as a solitary pulmonary nodule(SPN) or as a cause of bronchial obstruction. The incidence, once minimal, is increasing in Korea. To get clinical spectrum about the tumor, we analyzed all the reported cases in Korea since 1964. Methods: We reviewed the clinical, radiological and pathological findings of 13 patients of intrapulmonary or endobronchial hamartomas in Severance Hospital and of 38 reported cases in Korea published in literatures from 1964 to 1992 retrospectively. Results: Including 17 endobronchial hamartomas, 54 cases were studied. There were 25 men and 29 women, with a mean age of 47.2 years; 45.3 years in endobronchial type and 51.3 years in parenchymal type. Pulmonary symptoms were present in 8 patients (22%) of intrapulmonary type and in all patients of endobronchial type: cough (65%), dyspnea (53%), sputum (35%), fever (29%) in order. On chest X-rays, atelectasis was seen in 10 patients (59%) in endobronchial type; but SPN was noted in 36 patients (97%) of intrapulmonary type. Calcification was present in 7 intapulmonary hamartomas (23%); but is in 2 endobronchial hamartomas (12%). The diagnostic yield was 6 out of 14(43%) in endobronchial ones; 4 out of 7(57%) in intrapulmonary ones. Fifty patients underwent operations as follows: lobectomy (28), enucleation (8), resection (8), bilobectomy (4), pneumonectomy (2). The hamartomas were 1.2 times more common in the right lung; mean transverse diameter at the time of operation was 2.3 cm in endobronchial type, 3.8 cm in intrapulmonary ones. Chondroid components were present in 11(65%) of 17 endobronehial ones but in 30(91%) of 33 intrapulmonary hamartomas. No malignant changes were seen perioperative period and up to early 1993. Conclusion: The younger age in endobronchial hamartomas, the preponderance of the female sex and the more incidence in the right lung, and the diagnostic choice of lobectomies were different from the studies of the Western countries.

• Tuberculosis and Respiratory Diseases
• /
• v.52 no.2
• /
• pp.179-185
• /
• 2002

A bronchus-associated lymphoid tissue(BALT) lymphoma of the lung is a rare disorder of patients with Sj$\ddot{o}$gren's syndrome. A 49-year-old woman was admitted for an evaluation of exertional dyspnea and general weakness which had persisted for two years. The patient had suffered from dry mouth and dry eyes for five years. The physical examinations showed a coarse breath sound with inspiratory crackles on the whole lung field, particularly on the both basal lungs. The laboratory data disclosed high titers of anti-nuclear antibodies, and anti-SSA (Ro), and anti-SSB (La) antibodies. Chest radiographs demonstrated the presence of bilateral, diffuse, reticulonodular densities in both lungs. Thin-section CT scans showed diffusely distributed mosaic pattern of an inhomogeneous attenuation extending over the entire lung zone. The histological findings from an open-lung biopsy specimen revealed an accumulation of lymphoid cells around the bronchioles and an extension of malignant lymphoma cells from the bronchiolar epithelium toward the alveolar space. Immunohistochemically, the neoplastic cells reacted positively to the CD 20 antigen and were focally positive for the UCHL 1 antigen. The histological diagnosis was consistent with a low grade marginal zone B-cell lymphoma originating in the BALT. Here, we present a case of a histologically proven BALT lymphoma of the lung in a patient with primary Sj$\ddot{o}$gren's Syndrome.

• Tuberculosis and Respiratory Diseases
• /
• v.50 no.1
• /
• pp.106-116
• /
• 2001

Background : Pulmonary thromboembolism is relatively frequent and potentially fatal. However, it is commonly misdiagnosed. The incidence of pulmonary thromboembolism is not decreasing despite advances in diagnosis and effective prophylatic measures. Its potential for significant sequela necessitates a prompt diagnosis and treatment. Unfortunately, there are many difficulties and problems regarding accurate diagnosis. There is a low prevalence of deep vein thrombosis and pulmonary thromboembolism in Korea and only few reports on this subject are available. Method : The clinical features of 36 patients, who were diagnosed with pulmonary thromboembolism at the Korea University medical center, were reviewed. Results : 1) There was no significant difference in prevalence between men an women, and the mean age was 50.9 years in men 59.2 years in women. 2) The frequent causes of pulmonary thromboembolism were malignancies (22.2%), surgery (22.2%), and heart disease(8.2%). Specific causes were not identified in 33.3%. 3) The most common symptom was dyspnea(72.2%), and the most common sign was tachypnea(61.1%). 4) The EKG findings were normal in 28.6%, an S1Q3T3 pulmonale pattern in 25.7%, ST or QRS changes in others. 5) The chest X-ray findings indicated pulmonary infiltration in 37.5%, cardiomegaly in 15.6%, pleural effusion in 12.5%, and normal in 27.8%. The perfusion lung scan showed a high probability in 66.7%, and intermediate or low probability in 33.3%. 6) The pulmonary arterial pressure(PAP) in the high probability groups was 57.9mmHg with a higher mortality rate(35%). Conclusion : Pulmonary thromboembolism is not uncommon in Korea and its clinical features do not differ greatly from thase reported in the literature. When pulmonary thromboemblism of unknown causes are diagnosed, a search for an occult malignancy is recommended. Rapid diagnosis and treatment are achieved when thromboemblism is suspected.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.1
• /
• pp.107-115
• /
• 1998

Background: Chronic eosinophilic pneumonia(CEP) presents with profound systemic symptoms, including fever, malaise, night sweats, weight loss, and anorexia together with localized pulmonary manifestations such as cough, wheeze, and sputum. It is an illness occurring predominantly in women. The chest radiogragh shows fluffy opacities that often have a characteristic peripheral configuration. The hallmark of CEP is the peripheral blood eosinophilia and a prompt response to oral corticosteroid therapy. We investigated characteristics of eleven patients of chronic eosinophilic pneumonia, reported in Korea. Method: There were eleven reports of CEP from 1980 to 1996, including three cases experienced in our hospital. The journals were analysed in respects of clinical history, laboratory, and radiographic findings. Results: 1) Male vs. female ratio is 3 : 8. The peak incidence occurred in forty and fifty decades. The atopic diseases were present in 6 cases. Asthma was the commonest manifestation 2) The presenting symptoms were as follows: cough, dyspnea, sputum, weight loss, fever, general weakness, night sweats, urticaria with the descending incidence. 3) Peripheral blood eosinophilia was present in all patients(mean ; 38.4%) and serum IgE level was elevated in nine patients(mean ; 880IU/ml). Conclusion: The diagnosis of chronic eosinophilic pneumonia is based on classic symptoms, including fever, night sweats, weight loss with a typical roentgenogram of peripheral pulmonary infiltrates and peripheral blood eosinophilia, and that is confimed by lung biopsy and/or bronchoalveolar lavage. Chronic eosinophilic pneumonia is responsive to corticosteroid promptly and recommended at least 6 months of therapy to prevent relapse.

• Tuberculosis and Respiratory Diseases
• /
• v.43 no.6
• /
• pp.925-935
• /
• 1996

Background : In order to elucidate one of the pathogenic mechanisms of ARDS associated with pulmonary surfactant and oxidant injury, acute lung injury was induced by N-nitroso N-methylurethane (NNNMU). In this model, the role of phospholipase $A_2$ ($PLA_2$), surfactant, gamma glutamyl transferase (GGT) and morphology were investigated to delineate one of the pathogenic mechanisms of ARDS by inhibition of $PLA_2$ with high dose of dexamethasone. Method: Acute lung injury was induced in Sprague-Dawley rats by NNNMU which is known to induce acute lung injury in experimental animals. To know the function of the alveolar type II cells, GGT activity in the lung and bronchoalveolar lavage was measured. Surfactant phospholipid was measured also. $PLA_2$ activity was measured to know the role of $PLA_2$ in ARDS. Morphological study was performed to know the effect of $PLA_2$ inhibition on the ultrastructure of the lung by high dose of dexamethasone. Results : Six days after NNNMU treatment (4 mg/kg), conspicuous pulmonary edema was induced and the secretion of pulmonary surfactant was decreased significantly. In the acutely injured rats' lung massive infiltration of leukocytes was observed. At the same time rats given NNNMU had increased $PLA_2$ and GGT activity tremendously. Morphological study revealed bizarre shaped alveolar type II cells and hypertrophied lamellar bodies in the cytoplasm of the alveolar type II cells. But after dexamethasone treatment (20 mg/kg, for six days) in NNNMU-treated rats, these changes were diminished i.e. there were decrease of pulmonary edema and increase of surfactant secretion from alveolar type D cells. Rats given dexamethasone and NNNMU had decreased $PLA_2$ and GGT activity in comparison to NNNMU induced ARDS rats. Conclusion : Inhibition of $PLA_2$ by high dose of dexamethasone decreased pathological findings caused by infiltration of leukocytes and respiratory burst. Based on these experimental results, it is suggested that an activation of $PLA_2$ is the one of the major factors to evoke the acute lung injury in NNNMU-induced ARDS rats.

• Pediatric Infection and Vaccine
• /
• v.31 no.1
• /
• pp.75-82
• /
• 2024

Purpose: As the coronavirus disease 2019 (COVID-19) pandemic ended, the number of patients with respiratory syncytial virus (RSV) pneumonia increased during the spring/summer of 2022. This study aimed to analyze the clinical features and antibiotic usage of children hospitalized for RSV pneumonia in a recently established general hospital in Sejong city. Methods: In this retrospective review, we included inpatients of the Pediatric Department of Chungnam National University Sejong Hospital diagnosed with RSV pneumonia between March 2022 and April 2023. Patients were divided into 2 groups: with and without antibiotic treatment. Demographic data, initial presentations, and clinical courses were reviewed. Results: A total of 116 patients with RSV pneumonia were hospitalized during this period, of which 102 were analyzed, excluding 14 with underlying diseases or who did not fall within the definition of pneumonia. The median age was 17 months. Diagnoses of bacterial infections (acute otitis media and sinusitis) were documented in 9.8% of cases. Intravenous (IV) antibiotics were administered in 46% of cases. The group receiving IV antibiotics showed higher inflammatory levels (C-reactive protein; CRP), more infiltration on initial chest X-rays, and longer fever duration. There was no difference in the length of hospitalization between the groups with and without IV antibiotics. Conclusions: This study showed a tendency for the attending physician to prescribe IV antibiotics to patients with longer fever duration, pulmonary infiltrations on the initial chest X-ray, and higher CRP levels. However, given the high rate of IV antibiotic usage compared to previous studies, care should be taken in antibiotic use.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.4
• /
• pp.500-512
• /
• 2000

Background : To evaluate the efficacy of two methods of obtaining lung recruitment to reduce ventilator-induced lung injury(VILI). Methods : Fifteen New-Zealand white rabbits were ventilated in the pressure-controlled mode while maintaining constant tidal volume(10 ml/kg) and fixed respiration rate. Lung injury was induced by repeated saline lavage (PaO2<100 mmHg), and the pressure-volume curve was drawn to obtain Pflex. The animals were then randomly assigned to three groups and ventilated for 4 hours. In the control group(n=5), positive end-expiratory pressure(PEEP) less than that of Pflex by 3 mmHg was applied throughout the study. In the recruitment maneuver(RM) group(n=5), RM(CPAP of 22.5 mmHg, for 45 seconds) was performed every 15 minutes in addition to PEEP level less than Pflex by 3 mmHg This phrase is unclear. In the Pflex group, PEEP of Pflex was given without RM. Gas exchange, lung mechanics, and hemodynamics parameters as well as pathology were examined. Results : 1) Both the control and RM groups showed decreasing tendency in PaO2 with time. There was significantly decreased PaO2 at 4 hr compared to Ihr(p<0.05). But in the Pflex group, PaO2 did not decrease with time(p<0.05 vs other groups at 3, 4 hr). PaCO2 did not show significant difference among the three groups. 2) There was no significant difference in static compliance and plateau pressure. Mean blood pressure and heart rate also did not show any significant difference among the three groups. 3) The pathologic exam showed significantly less neutrophil infiltration in the Pflex group than in the control group(p<0.05). There was borderline significant difference in hyaline membrane score among the groups (p= 0.0532). Conclusion : Although recruitment maneuver of the injured lung may be important in decreasing VILI, it alone may not be sufficient to minimize VILI.

• Tuberculosis and Respiratory Diseases
• /
• v.53 no.2
• /
• pp.101-112
• /
• 2002

Background : Toluene diisocyanate(TDI) is a leading cause of occupational asthma. However, the pathogenesis of TDI-induced asthma is largely unknown because there is no suitable animal model. Materials and Methods : We developed a murine model of TDI-induced asthma by performing two sensitization with 3% TDI and one challenge with 1% TDI using ultrasonic nebulization. Results : Similar to occupational asthma in humans, murine TDI-induced asthma includes findings 1) increased inflammatory cells, including neutrophils and eosinophils, 2) histologic changes, including infiltration of inflammatory cells around bronchioles, thickened airway epithelium, contraction of bronchioles, and accumulation of mucus and debris in the bronchioles, 3) increased MMP-9 activity in inflammatory cells in the airway lumen, 4) airway hyperrespnosiveness. Administraion of an MMP inhibitor, MMPI-I, remarkably reduced all these pathophysiological findings. Conclusion : Therefore, we conclude that TDI-induced occupational asthma is associated with the induction of MMP-9 in inflammatory cells, and the inhibition of MMP-9 may be a good therapeutic strategy.