• Tuberculosis and Respiratory Diseases
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• v.55 no.2
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• pp.140-153
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• 2003

Background : The cell-mediated immune reaction to tuberculosis infection involves a complex network of cytokines. The extent of inflammation, tissue damage and severity of the disease suggested to be determined by the balance between extent and duration of the proinflammatory cytokine response versus those of the suppressive cytokines. The systemic cytokine response in pathogenesis of tuberculosis can be assessed by measuring serum cytokine levels. Method : Serum interleukin-1 beta(IL-$1{\beta}$), IL-2, IL-4, IL-6, IL-10, IL-12(p40), tumor necrosis factor-alpha(TNF-${\alpha}$), interferon-gamma(IFN-${\gamma}$) and transforming growth factor-beta(TGF-${\beta}$) levels were measured in 83 patients with pulmonary tuberculosis, 10 patients with endobronchial tuberculosis before treatment and 20 healthy subjects by using a sandwich ELISA. In patients with pulmonary tuberculosis, they were divided into mild, moderate and far advanced group according to the severity by ATS guidelines. To compare with those of pretreatment levels, we measured serum IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-10, IL-12(p40), TNF-${\alpha}$, IFN-${\gamma}$ and TGF-${\beta}$ levels in 45 of 83 patients with pulmonary tuberculosis after 2 and 6 months of treatment. Results : 1) In sera of patients with active pulmonary tuberculosis(n=83), IL-$1{\beta}$, IL-6(p<0.05), TNF-${\alpha}$, and IFN-${\gamma}$ were elevated and TGF-${\beta}$ was decreased comparing to control. IL-2, Il-12(p40), IL-4 and IL-10 were similar between the patients with tuberculosis and control. 2) In endobronchial tuberculosis, IL-6 and TNF-${\alpha}$ were elevated and TGF-${\beta}$ was decreased comparing to control. IL-12(p40) seemed to be elevated comparing to pulmonary tuberculosis. 3) Far advanced tuberculosis showed markedly elevated IL-6 and IFN-${\gamma}$ level(p<0.05). 4) The significant correlations were noted between IL-1, IL-6 AND TNF-${\alpha}$ and between IL-12, Il-2 and IL-4(p<0.01). 5) After 2 and 6 months of standard treatment, the level of IL-6 and IFN-${\gamma}$ was significantly decreased(p<0.05). Conclusion : These results showed that an altered balance between cytokines is likely to be involved in the extent of inflammation, tissue damage and severity of the disease tuberculosis. But, it should be considered diversities of cytokine response according to type of tuberculosis and immunity in clinical application and interpreting future studies.

• Biomedical Science Letters
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• v.2 no.2
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• pp.133-151
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• 1996

After cardiac surgery, it has been recognized that various complications were associated with injured humoral and cellular immunity by cardiopulmonary bypass(CPB). Especially, in postoperative pulmonary dysfunction, transpulmonary leukostasis followed complement activation and inflammatory responses are major pathogen. Some studies have showed that pretreated-corticosteroids before CPB protected postoperative pulmonary dysfunction. Corticosteroids may inhibit complement and leukocyte activation. On based previous studies, present investigator determined changes of leukocyte counts and transpulmonary leukostasis during cardiac surgery and postoperative periods. For the evaluation of postoperative pulmonary function and edema, $PaO_2$ and chest X-ray were compared between pre-CPB and post-CPB. Fever and other parameters were also observed postoperatively. The aim of this study was to define for the prophylactic effects of corticosteroid(Solu-Medrol: 30mg/kg) on all the researched parameters. This study was prospectively designed with randomized-blind fashion for 50 patients undergoing cardiac surgery. According to the purpose of study, all patients were divided into placebo and steroid group. : Placebo group was 25 patients received normal saline(not corticosteroid), and steroid group was 25patients received corticosteroid(Solu-Medrol: 30mg/kg) before initiation of CPB. The results of study were summarized as follows. 1. Total peripheral leukocyte counts decreased significantly at 5 minutes of CPB in all patients(P<0.01), and began to increase progressively at later periods of CPB with neutrophilia. The significant rise remained at postoperative 7th day(P<0.05). 2. During partial CPB, transpulmonary leukostasis occurred in placebo group(P<0.001), whereas it was prevented in steroid group. 3. In both groups, peripheral lymphocyte counts were stable during CPB, but began to reduce at time of intensive care unit(ICU) and the lymphocytopenia remained until postoperative 3rd day. The lymphocyte counts recovered on postoperative 7th day. 4. In both groups, peripheral counts of monocyte were relatively stable in the early peroid of CPB, and increased gradually in the later periods of CPB. This significant monocytosis remained throughout postoperlative periods(P<0.05). 5. The mean value of postoperative $paO)_2$ was lower than that of pre-CPB in placebo group(P=0.01) but didn't significant in steroid group(P=0.90). In the incidence of pulmonary edema signs and fever, placebo group was higher than steroid group(P=0.001, p=0.01, respectively). However mechanical respiratory supporting and care periods at intensive care unit were not significant difference between two groups(P>.0.05).With the above results, the investigator concluded that leukocyte activation and pulmonary sequestration were caused by cardiac surgery with CPB and demonstrated that high dose corticosteroid will provide prophylactic effect for pulmonary leukostasis and higher neutrophilia. These effects may ameliorate postoperative pulmonary dysfunction and contribute to postoperative less morbidity. However, further study should be performed because postoperative lymphocytopenia continued for 3 days in both groups, which may suspected damage or suppression of cell-mediated immunity with used corticosteroid.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.449-458
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• 2003

Background : Cyclosporin A(CsA) and tacrolimus(FK506) have been widely used as immunosuppressants. The effects of CsA, or FK506, on the $I{\kappa}B/NF-{\kappa}B$ pathway have been shown to vary according to the cell type. However, their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway have not been reported in bronchial epithelial cells. In this study, the effects of CsA and FK506 on the $I{\kappa}B/NF-{\kappa}B$ pathway in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages were evaluated. The relationship between their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway and $I{\kappa}B$ kinase(IKK) activity was also investigated. Methods : BEAS-2B and A549 cells, pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes were used. The cells were pre-treated with CsA, or FK506, for various time periods, followed by stimulation with TNF-${\alpha}$, LPS or IL-$1{\beta}$. The $I{\kappa}B{\alpha}$ expressions were assayed by Western blot analyses. The IKK activity was evaluated by an in vitro immune complex kinase assay, using GST-$I{\kappa}B{\alpha}$ as the substrate. Results : Neither CsA nor FK506 affected the level of $I{\kappa}B{\alpha}$ expression in any of the cell types used in this study. CsA pre-treatment inhibited the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells. In contrast, the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation was not affected by FK506 pre-treatment. However, FK506 suppressed the cytokine-induced $I{\kappa}B{\alpha}$ degradation in the pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes. The inhibitory effect of CsA, or FK506, on $I{\kappa}B{\alpha}$ degradation was not related to IKK. Conclusions : CsA and FK506 suppressed the $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages, so this may not be mediated through IKK.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.1012-1021
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• 1998

Background : It is known that airway inflammation is present in most patients with asthma, but the relationship between symptoms and the severity and nature of airway inflammation has not been established. Cough variant asthma is defined as an asthma in which the dominant symptom is cough, and the condition can be successfully treated with inhaled steroids. This study was performed to evaluate the time course of bronchial responsiveness according to an inhaled anti-inflammatory therapy and the factors which affect the resolution of bronchial responsiveness, and an efficacy of nedocromil to cough asthma. Method: A prospective study for the investigation of bronchial responsiveness according to an inhaled anti-inflammatory treatment in sixty-one cough asthmatics was performed. Twenty-three entered budesonide ($400{\mu}g{\times}2/day$), twenty-two entered nedocromil ($4mg{\times}2/day$) and sixteen patients entered combined group. The bronchial hyperresponsiveness (BHR) was estimated by methacholine challenge test using counted breath method. The symptom was estimated by 'symptom score'. Reevaluation of BHR and symptom was performed at 2 month after treatment, and if BHR was not resoluted at this time, regarded as a non-responder, and then follow-up of BHR and symptom was performed at 4- and/or 6 month after treatment. Results: The improvement of BHR and symptom was significant in 2 month (p<0.05), but there was no change of them during follow-up period of 4- and/or 6 month in non-responders. In comparison of allergic markers such as serum total IgE, peripheral eosinophil count and skin test reactivity between responders and non-responders, there was no difference in each other. However, in comparison of other factors such as cumulative pack-years, symptom duration, age, gender, and the initial degree of PC20, there was a significant difference in each other(p<0.05). The percent of patients with the resolution of BHR in 2 month was not different in each group(p=0.95). There was no significant difference in the degree of improvement of BHR and symptom in each group. Conclusion: Bronchial responsiveness and symptom was not significantly improved in non-responders during follow-up period of 4- and/or 6 month. The effect of inhaled nedocromil was equivalent to that of inhaled steroid in cough asthmatics, and the response to combined treatment is not superior to that achieved by either of these agents used alone.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.118-126
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• 2001

Purpose : In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. Materials and Methods : From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was $48.2{\pm}7.9\;Gy$ in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at $4\~8$ weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. Results : An objective response was observed in 106 of 158 patients, giving a response rate of $67.1\%$. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only $29.2\%$ showed objective response in patients treated with dose less than 40 Gy, while $68.6\%\;and\;77.1\%$ showed major response in patients with $40\~50\;Gy$ and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Conclusion : Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non-irradiated liver volume.

• Radiation Oncology Journal
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• v.17 no.1
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• pp.9-15
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• 1999

Purpose : This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer, Materials and Methods : Firty-six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deli- ver 44 Gy using 1 OMV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylaetic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. Results : The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved En 30 (65$\%$) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50$\%$), anemia in 17 (37$\%$), thrombo- cytopenia in nine (20$\%$), alopecia in nine (20$\%$), nausea/vomiting in five (11$\%$), and peripheral neuropathy in one (2$\%$). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24$\%$) out of the total 246 cycles. No radiation esophagitis over grade 111 was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The overall and progression-free survival rates were 79$\%$ and 55$\%$ in 1 year, and 45'/) and 32% in 2 years, respectively, and the median survival was 23 months. Conclusion : Relatively satisfactory local control and suwival rates were achieved after the combined chemotherapy and radiation therapy with mild to moderate acute morbidities in limited disease small cell lung cancer.

• The Journal of the Korean Society for Microbiology
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• v.14 no.1
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• pp.79-87
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• 1979

The immunosuppressive activity of newcastle disease virus(NDV) and some possible role of interferon(C-IF) in viral suppression of immune response were evaluated by SRBC-induced delayed-type hypersensitivity(DTH), rosette formation in spleen cells, number of lymphocytes in peripheral blood, hemagglutinin and hemolysin response to SRBC in ICR mice sensitized with SRBC. When NDV was inoculated before or after sensitization of mouse with SRBC, virus caused a marked inhibition of DTH, and its depressive effect was dependent on the time of virus inoculation in relation to SRBC sensitization or challenge. Rosette formation of spleen cells was significantly reduced by NDV infection. The degree of the depression of rosette formation was more prominent in mice inoculated before sensitization than after sensitization and could be related to the amount of serum interferon induced by the virus. Humoral response to SRBC of virus infected mouse was significantly depressed when NDV was inoculated 24 or 48 hours before sensitization. However, there was no difference in the response when the virus was inoculated 9 hour before and at the same time of sensitization or even after that. Lymphocytes in peripheral blood of mice were markedly diminished in numbers when NDV was inoculated 48 and 24 hour before sensitization with SRBC, but they were slightly augmented when the virus was inoculated 9 hour before and at the same time of sensitization. When UV-inactivated or heat-inactivated NDV was injected to the mouse at the same time of sensitization with SRBC, DTH and rosette formation of spleen cells were slightly depressed. DTH and rosette formation in mice treated with crude-IF were generally depressed as com pared with those of control mice. These studies suggest that the NDV causes a significant depression of cell-mediated immunity, whereas the humoral immune response is not inhibited markedly, and that the depression of immune response by NDV infection may be caused by interferon produced by NDV and direct viral activity.

• The Korean Journal of Nuclear Medicine
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• v.37 no.4
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• pp.219-228
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• 2003

Purpose: The amount of salvaged myocardium is an important prognostic factor in patients with acute myocardial infarction (MI). We investigated if early Tl-201 SPECT imaging could be used to predict the salvaged myocardium and functional recovery in acute MI after primary PTCA. Materials and Methods: In 36 patients with first acute MI treated with primary PTCA, serial echocardiography and Tl-201 SPECT imaging ($5.8{\pm}2.1$ days after PTDA) were performed. Regional wall motion and perfusion were quantified with on 16-segment myocardial model with 5-point and 4-point scaling system, respectively. Results: Wall motion was improved in 78 of the 212 dyssynergic segments on 1 month follow-up echocardiography and 97 on 7 months follow-up echocardiography, which were proved to be salvaged myocardium. The areas under receiver operating characteristic curves of Tl-201 perfusion score for detecting salvaged myocardial segments were 0.79 for 1 month follow-up and 0.83 for 7 months follow-up. The sensitivity and specificity of Tl-201 redistribution images with optimum cutoff of 40% of peak thallium activity for detecting salvaged myocardium were 84.6% and 55.2% for 1 month follow-up, and 87.6% and 64.3% for 7 months follow-up, respectively. There was a linear relationship between the percentage of peak thallium activity on early redistribution imaging and the likelihood of segmental functional improvement 7 months after reperfusion. Conclusion: Tl-201 myocardial perfusion SPECT imaging performed early within 10 days after reperfusion can be used to predict the salvaged myocardium and functional recovery with high sensitivity during the 7 months following primary PTCA in patients with acute MI.

• Clinical and Experimental Pediatrics
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• v.48 no.3
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• pp.266-275
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• 2005

Purpose : Acute respiratory tract infections are the most common illnesses in children. The great majority of these infections involving lower respiratory tracts infections(LRTIs) are caused by respiratory viruses such as respiratory syncytial virus(RSV), parainfluenza virus(PIV), influenza virus (Flu), and adenovirus(ADV), etc. Our purpose was to determine seasonal epidemiology and clinical characteristic features of each viral infection. Methods : Nasopharyngeal aspirate(NPA)s were collected from 4,554 hospitalized children diagnosed as LRTIs on the first day of admission. The study period was from September 1998(Autumn) through May 2003(Spring). Respiratory viruses were detected in 881(19 percent) cases by isolation of the virus or by antigen detection method using indirect immunofluorescent staining. We reviewed the medical records of 837 cases retrospectively. Results : The identified pathogens were RSV in 485 cases(55 percent), PIV in 152 cases(17 percent), FluA in 114 cases(13 percent), ADV in 79 cases(9 percent) and FluB in 51 cases(6 percent). Outbreaks of RSV occurred every year, mostly in the November through December period and of PIV in the April through June period. LRTIs by FluA reached the highest level in January, 2002. FluB infection showed an outbreak in April, 2002. The clinical diagnoses of viral LRTIs were bronchiolitis in 395 cases(47 percent), pneumonia in 305 cases(36 percent), croup in 73 cases(9 percent) and tracheobronchitis in 64 cases(8 percent). Conclusion : Viruses are one of the major etiologic agents of acute LRTIs in chidren. Therefore, we must continue to study their seasonal occurrence and clinical features to focus on management, and also for reasons of prevention.

• Tuberculosis and Respiratory Diseases
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• v.44 no.1
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• pp.93-103
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• 1997

Background : Malnutrition is a common finding in patients with chronic obstructive pulmonary disease, especially in the emphysema group. Although the mechanism of malnutrition is not confirmed, it is believed to be a relative deficiency caused by hypermetabolism due to increased energy requirements of the respiratory muscles, rather than a dietary deficiency. Malnutrition in chronic obstructive pulmonary disease is not a merely coincidental finding. It is known that the nutritional status correlates with physiologic parameters including pulmonary function, muscular power, and exercise performance, and is one of the important and independent prognostic factors of the disease. Methods : Patients with chronic obstructive pulmonary disease Yongdong Severance Hospital from May, 1995 to March, 1996 and age-matched healthy control group were studied. Survey of nutritional intake, anthropometric measurements and biochemical tests were done to assess nutritional status. Relationship between nutritional status and FEV1 (forced expiratory volume at one second), which was a significant functional parameter, was assessed. Results : 1) The patient group was consisted of 25 males with mean age of 66.1years and FEV1 of $42{\pm}14%$ of predicted values. The control group was consisted of 26 healthy males with normal pulmonary function, whose mean age was 65.0 years. 2) The ratio of calorie intake/calorie requirement per day was $107{\pm}28%$ in the patient group, and $94{\pm}14%$ in the control group, showing a tendency of more nutritional intake in patient group(B=0.06). 3) There were significant differences between the patient group and control group in percent ideal body weight(92.8% vs 101.6%, p=0.024), body mass index($20.0kg/m^2$ VS $21.9kg/m^2$, p=0.015), and handgrip strength(29.0kg vs 34.3kg, p=0.003). However, there were no significant differences in triceps skinfold thickness, mid-arm muscle circumference, albumin, and total lymphocyte count between two groups. Percentage of underweight population was 40%(10/25) in the patient group, and 15%(4/26) in the control group. 4) The percent ideal body weight, triceps skinfold thickness, and mid-arm muscle circumference had significant correlation with FEV1. Conclusion : The patients with chronic obstructive pulmonary disease showed significant depletion in nutritional parameters such as body weight and peripheral muscle strength, while absolute amount of dietary intake was not insufficient. Nutritional parameters were well correlated with FEV1.