• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1114-1124
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• 1997

Background : Endothelin(ET) is a very potent vasoconstrictive peptide produced by endothelial cells of pulmonary artery. The endothelin level was increased in plasma of primary pulmonary hypertension and acute pulmonary thromboembolism and it was suggested that the endothelin might do a critical role in the cardiopulmonary dysfunction in these two conditions. But the exact mechanism of increase of ET has not been known. In these two conditions, platelet activation and thrombosis are the main pathophysiologic findings. So there is a possibility that the platelet might stimulate endothelin secretion from endothelial cells. Therefore, we performed this study to evaluate the role of platelet and its mediators on endothelin production in bovine pulmonary artery endothelial(BPAE) cells. Method : Bovine pulmonary artery endothelial cells, ATCC certified cell line 209, were cultured and treated with human platelets($10^6{\sim}10^8/ml$), thrombin (0.1~10u/ml), TGF-${\beta}1$(1~100uM), serotonin(1~100uM), and endotoxin(1ug/ml) in a final volume of 500ul for 18 hours. Levels of ir(immunoreactive)-ET in each conditioned medium were measured by a radioimmunoassay specific for ET. Result : The increase of ir-ET levels was platelet number and time dependent over 18 hours. When washed human platelets were added($10^8/ml$), the ir-ET levels were significantly higher than that of control(p<0.05) at 8 and 18 hours after culture. Subthreshold concentration of platelets($10^7/ml$) coincubated with endotoxin(1ug/ml) or subthreshold dose of thrombin(0.1u/ml) stimulated ir-ET secretion from BPAE cells significantly(p<0.05) compared with control. Thrombin(1ug/ml, 10ug/ml) and TGF-${\beta}1$(100pM, 1000pM) significantly increased ir-ET secretion from BP AE cells(p<0.05) compared with control, but serotoin(1~100uM) and endotoxin(1ug/ml) did not stimulate the ir-ET secretion. Conclusions : Platelets stimulate endothelin secretion from bovine pulmonary artery endothelial cells. The mechanism of increase of endothelin secretion seems to be a stimulation by platelet itself or by mediators, such as TGF-${\beta}1$, secreted from activated platelets. And, in this study, the priming effect of platelets on endothelin secretion from BPAE cells could be another possibility.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.369-377
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• 1997

Purpose : This study was Performed to identify the histopathologic feature by the reevaluation of the Pathologic specimen of the cervical tumors and to evaluate the clinical findings and the treatment results of the patients with small cell carcinoma of the cervix treated by radiotherapy. Materials and Methods : 2890 patients with cervical carcinoma received radiotherapy at the Department of Radiation Oncology. Yonsei Cancer Center, Yonsei University College of Medicine between October 1981 and April 1995. Of the 2890 patients in this data base, sixty were found to have small cell carcinomas $(2.08\%)$. Among them thirty six patients were transferred from other hospitals. the biopsy specimens of those Patients were not available. So we could review the slides of the other twenty four patients who were diagnosed at our hospital. Twenty four patients with small cell carcinoma of the cervix were analyzed retrospectively based on the assessment of H & E staining and other four immunohistochemical stains for neuroendocrine differentiation (neuron specific enolase, chromogranin. synaptophysin and Grimelius stain). And we also evaluate the Patients and tumor characteristics. response to radiation. patterns of failures, 5 year overall and disease free survival rates. Results : Thirteen tumors were neuroendocrine carcinomas(13/24 = $54.2\%$) and eleven tumors were squamous carcinomas, small cell type (11/24 = $47.8\%$) based on the assessment of H & E staining and other four neuroendocrine marker studies. So we classified the Patients two groups as neuroendocrine carcinoma and small cell type of squamous carcinoma, Among the 13 neuroendocrine carcinomas, five were well to moderately differentiated tumors and the other eight were Poorly differentiated or undifferentiated ones. The median age was 54 years old (range 23-79 years). Eight Patients had FIGO stage IB disease, 12 had stage 11, 3 had stage III and one had stage IV disease, Pelvic lymph node metastases were found in five Patients $(20.8\%)$. three of them were diagnosed by surgical histologic examination and the other two were diagnosed by CT scan. There was no difference between two histopathologic groups in terms of patients and tumor characteristics. response to radiation. 5 year overall and disease free survival rates. However the distant metastases rate was higher in neuroendocrine carcinoma Patients (6/13:$46.2\%$) than in small cell type of squamous carcinoma Patients (2/11:$18.2\%$), but there was no statistically significant difference because of the small number of patients (P>0.05). Conclusion : More than half of the small cell carcinoma of the cervix patients were neuroendocrine carcinoma (13/24 : $54.1\%$) by reevaluation of the biopsy specimen of the cervical tumors. The tendency of distant metastases of the neurolndocrine carcinoma was greater than those of the small cell type of squamous carcinoma $(46.2\%\;vs.\;18.2\%)$. But there were no differences in the patients and tumor characteristics and other clinical treatment results in both groups. These data suggest that radical local treatment such as radiotherapy or radical surgery combined with combination systemic cytotoxic chemotherapy might provide these patients with the best chance for cure.

• Journal of Genetic Medicine
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• v.5 no.2
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• pp.105-110
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• 2008

Purpose: Preecalmpsia is a pregnancy-specific disorder that reflects widespread endothelial dysfunction resulting from increases of adhesion molecule expression. Intercellular adhesion molecule-1 (ICAM-1) is involved in the pathogenetic mechanisms responsible for preeclampsia, and ICAM-1 plasma levels and/or function is genetically influenced. Therefore, we evaluated the distribution of ICAM-1 gene K469E polymorphism in pregnant Korean women with preeclampsia and evaluated the association between this polymorphism and preeclampsia. Methods: The K469E polymorphism was analyzed in peripheral blood samples from 197 preeclamptic pregnancies and 193 normotensive pregnancies by a SNapShot kit and an ABI Prism 3100 Genetic analyzer. Results: Genotypic and allelic frequencies of ICAM-1 gene polymorphism (K469E) did not differ between preeclamptic and normotensive pregnancies. The distributions of the KK, KE, and EE genotypes were 40.6%, 43.7%, and 15.7%, respectively, in preeclamptic pregnancies and 38.9%, 45.1%, and 16.1%, respectively, in normotensive pregnancies. The frequencies of K and E alleles were 0.62 and 0.38, respectively, in preeclamptic pregnancies and 0.61 and 0.39, respectively, in normotensive pregnancies. By multiple logistic regression analysis, there was no increased risk of preeclampsia in subjects with ICAM-1 KE (OR, 1.08; P=0.74) or EE (OR, 1.07; P=0.88) genotypes. Conclusion: This study suggests that the ICAM-1 gene K469E polymorphism does not associate with an increased risk of preeclampsia in pregnant Korean women.

• The Korean Journal of Nuclear Medicine Technology
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• v.16 no.2
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• pp.149-155
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• 2012

Purpose : Serum insulin levels are useful indicator which of reflecting the function of insulin secretion in pancreatic ${\beta}$ cell and diagnosis of diabetes, differentiating the cause of impaired glucose tolerance. Insulin measurement kits have shown some differences in many ways such as test methods as well as quality control. The purpose of this study was to evaluate the diagnostic performance of seven manufacturing companies commercial kits. Materials and Methods : The values of insulin measured by three manufacturing companies (Biosource, Siemens, TFB) with 59 samples in August 2009 were compared with those measured by four manufacturing companies (Immunotech, Izotope, BNIBT, Cisbio) with 68 samples in December 2011. We evaluated precision, recovery rate, dilution test and correlation of serum insulin measurement using seven manufacturing company kits. Statistical program SPSS 12.0 was used for the verification of results. Results : The coefficients variation of the precision on all seven different kits were showed within 5.0%. Recovery rate of Biosource, Siemens, TFB kits on three different levels showed 94.2~103.7%, 99.0~104.6%, 99.7~107.6% respectively. Immunotech, Izotope, BNIBT, Cisbio were 93.5~99.1%, 91.4~99.1%, 99.2~131.0%, 84.8~102.3% respectively. There was strong correlation between the measurement of insulin by Biosource kit and that by two commercial kits, Siemens (R2=0.96), TFB (R2=0.99). There was good correlation between the measurement of insulin by TFB kit and that by three commercial kits, Immunotech (R2=0.97), Izotope (R2=0.96), Cisbio (R2=0.97). In the dilution test performed with more than 200 ${\mu}IU/ml$ high concentration samples, samples with diabetes correctly was measured in all seven manufacturing kits. However, as measured with insulinoma samples TFB, Siemens, Izotope, Cisbio kits were correctly measured, but Biosource and Immunotech kits were measured 47.4 ${\mu}IU/ml$, 72.3 ${\mu}IU/ml$, respectively. Conclusion : Serum Insulin radioimmunoassay kits were showed excellent precision, correlation and good recovery rate. However, some kits were not measured correctly in the high concentration insulin values. when selecting a kit should be considered many factors that cost effectiveness, compatible for automation equipment, high performance kit, the environment for each laboratory such as reaction time and reporting time.

• 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.

• Journal of The Korean Society of Grassland and Forage Science
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• v.27 no.2
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• pp.93-100
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• 2007

This study was conducted to determine the effects of different levels (10, 12 and 15%) of crude protein (CP) in total mixed ration (TMR) on dry matter intake, digestibility and nitrogen balance of Korean black goats in the stage of early pregnancy and to obtain information on their optimal dietary levels of CP. In the present study, 12 Does of Korean black goats in the early pregnancy were allotted to four unreplicated groups by dietary level of CP and then they were housed in individual metabolism cages with completely randomized design throughout 30 days with 20 days adaptation and 10 days collection periods. Does in Control were fed a conventional diet and does in TMR10, TMR12 and TMR15 were fed a diet adjusted to about 10, 12 and 15% CP, respectively. Dry matter(DM) contents ranged from 89 to 91% in treatments. There were no differences fur fiber contents among three CP levels of TMR, showing that ADF and NDF had 18.57 to 19.85, and 53.41 to 54.80, respectively. Crude protein contents for three TMR treaements had 10.61, 12.15 and 14.97%, respectively. However, non-fibrous carbohydrate (NFC) contents decreased with increasing CP levels in treatments. Meanwhile, Intakes of DM, nutrients and digestible nutrients were significantly (p<0.05) higher in TMR15 and control than in TMR10 and TMR12. Moreover, DM intake per metabolic body weight and theit ratio per body weight was significantly (p<0.05) higher for control and TMR15 than other treatments. DM digestibility was not significantly different among treatments, but ether extract digestibility of treatments was significantly (p<0.05) higher than that of control, but there was no significant difference among treatments. Nitrogen retention significantly (p<0.05) increased with increasing CP levels in TMR, and TMR15 was highest among treatments. Our results showed that the increasing CP levels in TMR increased DM intake and nitrogen retention and suggested that the optimal dietary CP levels under TMR feeding system in early pregnant Korean black goats could be estimated for at least 15%.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.360-378
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• 1997

Background : Severe acute lung injury(ALI), also known as the adult respiratory distress syndrome(ARDS), is a heterogenous nature of dynamic and explosive clinical synrome that exacts a mortality of approximately 50%. Endotoxin(ETX) is an abundant component of the outer membrane of gram-negative bacteria capable of inducing severe lung injury in gram-negative sepsis and gram-negative bacterial pneumonia, which are among the most common predisposing causes of ARDS. The influx of PMNs into airway tissue is a pathological hallmark of LPS-induced lung injury. And there is a substantial evidence suggesting that cytokines are important mediators of lung injury in gram-negative sepsis. However, the kinetics of phagocytes and cytokines by an exact time sequence and their respective pathogenic importance remain to be elucidated. This study was performed to investigate the role of phagocytes and proinflammatory cytokines in ETX-induced ALI through a time course of changes in the concentration of protein, $TNF{\alpha}$ and IL-6, and counts of total and its differential cells in BALF. The consecutive histologic findings were also evaluated. Method : The experimental animals, healthy male Sprague-Dawley, weighted $200{\pm}50g$, were divided into control- and ALI- group. ALI was induced by an intravenous administration of ETX, 5mg/kg. Above mentioned all parameters were examined at 0(control), 3, 6, 24, 72 h after administration of ETX. $TNF{\alpha}$ and IL-6 cone. in BALF were measured by a bioassay. Results : The protein concentration and total leukocyte count(TC) in BALF was significantly increased at 3h compared to controls(p < 0.05). The protein conc. was significantly elavated during observation period, but TC was significantly decreased at 72h(p < 0.05 vs. 24h). There was a close relationship between TC and protein cone. in BALF(r = 0.65, p < 0.001). The PMN and monocyte count was well correlated with TC in BALF, and the correlation of PMN(r = 0.97, p < 0.001) appeared to be more meaningful than that of monocyte(r = 0.61, p < 0.001). There was also a significant correlation between protein cone. and PMN or monocyte count in BALF(PMN vs. monocyte : r = 0.55, p < 0.005 vs. r = 0.64, p < 0.001). The count of monocyte was significantly elavated during observation period though a meaningful reduction of PMN count in BALF at 72h, this observation suggested that monocyte may, at least, partipate in the process of lung injury steadly. In this study, there was no relationship between IL-6 and $TNF{\alpha}$ cone., and $TNF{\alpha}$ but not IL-6 was correlated with TC(r = 0.61, p < 0.05) and monocyte(r = 0.67, p < 0.05) in BALF only at 3, 6h after ETX introduced. In particular, the IL-6 cone. increased earlier and rapidly peaked than $TNF{\alpha}$ cone. in BALF. In histologic findings, the cell counts of lung slices were increased from 3 to 72h(p < 0.001 vs. NC). Alveolar wall-thickness was increased from 6 to 24h(p < 0.001 vs. NC). There was a significant correlation between the cell counts of lung slices and alveolar wall-thickness(r= 0.61, p < 0.001). This result suggested that the cellular infiltrations might be followed by the alterations of interstitium, and the edematous change of alveolar wall might be most rapidly recovered to its normal condition in the process of repair. Conclusion : We concluded that although the role of PMN is partly certain in ETX-induced ALI, it is somewhat inadequate to its known major impact on ALL Alveolar macrophage and/or non-immune cells such as pulmonary endothelial or epithelial cells, may be more importantly contributed to the initiation and perpetual progression of ETX-induced ALI. The IL-6 in ETX-induced ALI was independent to $TNF{\alpha}$, measured by a bioassay in BALF. The early rise in IL-6 in BALF implies multiple origins of the IL-6.

• Journal of Chest Surgery
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• v.36 no.8
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• pp.545-558
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• 2003

Adult respiratory distress syndrome (ARDS) is of particular interest because of its severity of the associated lung injury and its high mortality. However, the pathophysiologies of ARDS in infant and childhood groups are still not well clarified inspite of many previous investigations. To investigate the time course of pathophysiology of ARDS in infant and childhood groups, this study was designed with experimental endotoxin-induced ARDS model using young rabbits (8 week-old). Material and Method: Rabbits were divided into the control group (n=8) and the endotoxin-treated group (n=32). The endotoxin group was subdivided into 4 groups by the sampling times as 3, 6, 12 and 24 hr-groups (G- $E_{3,6,12,24,}$ each n=8). The experimental ARDS was made by a bolus injection of endotoxin (Escherichia coli serotype 055 : B5, 0.50 mg/kg) via rabbit ear vein. For evaluation of the hematologic and inflammatory markers, and superoxide dismutase (SOD) concentrations, the blood samples were taken from the heart. The bronchoalveolar lavage fluid (BALF) were obtained for analysis of the leukocytes and protein concentration. With biopsy of the lung, histopathologic changes of the lung were also evaluated. Result: In the endotoxin groups, significant leukopenia (owing to pancytopenia) occurred in 3 and 6-hr groups, which was followed by significant leukocytosis (owing to neutrophilia) in the 12 and 24-hr groups (p<0.05). Serum levels of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1 $\beta$ (IL-1 $\beta$) in the endotoxin groups were higher than those of control group (p<0.05). Serum levels of superoxide dismutase (SOD) of G- $E_{3}$ and G- $E_{6}$ were higher than those of control group, whereas those of G- $E_{12}$ were lower than those of control groups (p<0.05). Total leukocyte counts and protein con-centrations in BALF were significantly elevated in the endotoxin groups compared to the control group (p < 0.05). The hemorrhagic pattern of BALF showed occurred in the endotoxin groups. The endotoxin groups (in G- $E_{6}$) had severe infiltration of inflammatory cells (lymphocyte and monocyte) in the pulmonary interstitium and parenchyma, migrations of neutrophil and eosinophil into alveolar spaces and interstitial widening, which are the evidences of acute lung injury. In the endotoxin groups, there were significant positive correlations between the BALF findings and the immunologic markers (TNF-$\alpha$, IL-1$\beta$, SOD) (p<0.05). Conclusion: Severe acute lung injury occurred in all the endotoxin-treated rabbits. The pathophysiologic findings were so progressive until 6-hr by time dependant pattern, and then recovered slowly, Variable hematologic, immuno-logic, and pathologic factors were well correlated in the development and progression of endoxin-induced lung injury. The pathophysiologic responses were sensitive and rapid in young rabbit Young rabbit seemed to be a useful experimental animal model for infant and childhood groups.roups.

• Radiation Oncology Journal
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• v.27 no.4
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• pp.218-227
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• 2009

Purpose: To investigate the radiobiologic effects of neutron and X-ray irradiation on DU-145 prostate carcinoma cells by identifying the differences of HIF-$1\alpha$ expression and apoptosis. Materials and Methods: Nude mice were injected with the human prostate cancer cell line, DU-145, and then irradiated with 2 Gy and 10 Gy X-rays, or 0.6 Gy and 3.3 Gy neutrons, respectively. The mice were sacrificed at 24 hours and 120 hours after irradiation. The expression levels of HIF-$1\alpha$, Bcl-2 and Bax were compared with immunohistochemical staining and western blotting. The apoptotic indexes were compared with the Terminal deoxynucleotidyl biotin-dUTP nick and labeling (TUNEL) assay. Results: At day 1, HIF-$1\alpha$ and Bcl-2 expression decreased, while Bax expression and the number of TUNEL positive cells increased in neutron irradiated groups for the control and X-ray irradiated groups. The Bcl-2/Bax ratio was significantly lower in the neutron irradiated groups regardless of dose (p=0.001). The same pattern of the differences in the expressions of the HIF-$1\alpha$, Bcl-2, Bax, Bcl-2/Bax ratio, and apoptotic indexes were indentified at day 5. HIF-$1\alpha$ expression was related with Bcl-2 (p=0.031), Bax (p=0.037) expressions and the apoptotic indexes (p=0.016) at day 5. Conclusion: Neutron irradiation showed a decrease in HIF-$1\alpha$, Bcl-2 expression, and Bcl-2/Bax ratio, but increased Bax expression regardless of dose. This study suggests that the differences radiobiological responses between photon and neutron irradiation may be related to different HIF-$1\alpha$ expression and subsequent apoptotic protein expressions.

• Clinical and Experimental Pediatrics
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• v.52 no.11
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• pp.1241-1248
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• 2009

Purpose:The etiology of Kawasaki disease (KD) is still unknown. Recently, an association between human coronavirus NL63 (HCoV-NL63) and KD was implicated. Hence, we attempted to determine the association between KD and acute respiratory viral infections. Methods:Nasopharyngeal aspirate samples were obtained from 54 patients diagnosed with KD at the Seoul National University (SNU) Children's Hospital and SNU-Bundang Hospital between October 2003 and September 2006. Viral diagnoses of 11 respiratory viruses were made using multiplex reverse transcriptase-polymerase chain reaction (RT-PCR): respiratory syncytial virus (RSV), adenovirus, rhinovirus (RV), parainfluenza viruses (PIVs) 1 and 3, influenza viruses (IFVs) A and B, human metapneumovirus (HMPV), human bocavirus (HBoV), HCoV OC43/229E, and HCoV-NL63. Clinical data were reviewed retrospectively. Results:The median age was 32 months (6 months-10.4 years). Respiratory symptoms were observed in 37 patients (69%). The following respiratory viruses were identified in 12 patients (22%): RV (n=4), PIV-3 (n=2), HBoV (n=2), and adenovirus, RSV, PIV-1, IFV-A, and HCoV-NL63 (n=1). Co-infection with PIV-3 and RV was observed in one patient. Respiratory symptoms were observed in 7 (58.3%) and 30 (71.4%) patients of the virus-positive and virus-negative groups (P>0.05). Response rate to intravenous immunoglobulin administration was 67% (n=8) and 86% (n=36) in the virus- positive and virus-negative groups (P>0.05). Conclusion:Respiratory symptoms were commonly observed in KD patients but the association between respiratory viruses and KD were not found. Large multicenter-based investigations are required to confirm the association between acute respiratory viral infections and KD.