• Pediatric Infection and Vaccine
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• v.7 no.1
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• pp.83-93
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• 2000

Purpose : Urabe AM-9 strain was known to be associated with increased aseptic meningitis. The reason for high incidence of vaccine-associated meningitis was known that nucleotide(nt) substituted form G to A at position 1081 of the hemagglutinin-neuraminidase(HN) gene and therefore, glutamic acid changed to lysine at amino acid 335. We assessed by comparing nt sequence of the HN gene form Urabe AM-9 strain with wild strain and documented the correlation between nt substitution and vaccine-associated meningitis. Methods : Two lots of Urabe AM-9 vaccine distributed in Korea and mumps wild strains isolated from 1998 through 1999 were analysed. Analysis was made by nt sequencing following amplification of HN gene by RT-PCR. Results : Nucleotide substitution at position 343, 1476, 1570 was not found in both Urabe AM-9 vaccines and wild strains. But analysis of vaccine strains and wild strains isolated from patients revealed substitution from G to A at nt 1081 of the HN gene. Therefore, it encodes lysine instead of glutamic acid at amino acid 335. There was no mixture from of G and A at nt 1081. Nt at 1470 of one lot of Urabe AM-9 vaccines changed from C to A after Vero cell passage. Nt at 1727 of vaccines and wild strains was substituted A to G, so it encodes glycine instead of aspartic acid. Conclusion : Nucleotide analysis of HN gene revealed that nt 1081 of Urabe AM-9 vaccines and wild strains had wild type AAA($Lys^{335}$) instead of variant type GAA($Glu^{335}$). The results of this study suggest that there was a probability of vaccine-associated meningitis due to Urabe AM-9 in Korea before. But incidence of actual side effect was not evaluated because there was no reporting system in Korea.

• Journal of Chest Surgery
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• v.40 no.5 s.274
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• pp.369-375
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• 2007

Background: Patients suffering with pectus carinatum complain of cosmetic problems when they stand and this in spite of wearing cloths. The standard surgical treatment of pectus carinatum is resection of the deformed cartilages, but the wide operative scar, post-operative pain and complications related with such an operation can occur. Therefore, we have peformed compressive brace therapy as a non-operative treatment for pectus carinatum and we observed the effects and the efficiency of this treatment. Material and Method: From January, 2001 to December, 2006, 109 patients wore the compressive brace for all day. The degree of satisfaction was evaluated after $6\sim9$ months of wearing the compressive brace. The degree of satisfaction was evaluated by a score of from $1\sim4$. A score of 1 was assigned when the status was worse, 2 when it was the same, 3 when there was partial improvement and 4 when remarkable improvement was observed. The degree of satisfaction was assessed subjectively by the parent if the patient was a child younger than middle school age, and the patients older than middle school age assessed the score themselves. Result: The mean score of the overall degree of satisfaction was $3.93{\pm}0.33$. Recurrence of pectus carinatum after removal of compressive brace occurred in 6 patients (5.5%) of the total 109 patients. But 4 patients of the total 6 recurred patients stopped wearing of compressive brace against our advice. The 6 recurred patients were re-corrected by re-wearing the compressive brace within 3 months after they originally removed the compressive brace. The complications were discomfort with initially wearing the compressive brace, which occurred in all patients, skin rash due to the compressive brace for 76 patients (69.7%) and skin discolorization with excessive compression for f6 patients (5.5%). The skin rash and discolorization returned to normal within a few months after removal of the compressive brace. Conclusion: This study demonstrated that non-surgical treatment with using the compressive brace for patients with pectus carinatum was effective, and especially for children and teenagers. Non-surgical treatment with using a compressive brace would be helpful for the patients suffering with pectus carinatum and who dislike surgical operations because of their fear about general anesthesia and operation-related complications. Yet long-term follow up is necessary to accurately evaluate the effectiveness of this compressive brace and the recurrences after removal of the compressive brace.

• Tuberculosis and Respiratory Diseases
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• v.65 no.5
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• pp.379-384
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• 2008

Background: Sputum decontamination with NALC-NaOH (N-acetyl-L-cysteine-sodium hydroxide) is known to better detect Mycobacterium tuberculosis (M. tb) by culture than that with using NaOH, which is widely used in Korean hospitals. In this report, sputum samples collected from pulmonary tuberculosis (TB) patients were treated with either NaOH or NALC-NaOH, and we compared the results of smear and culture positivity to determine whether the NALC-NaOH treatment method improves culture positivity in the sputum samples, and especially for those sputum samples that are smear negative and scanty. Methods: For each decontamination method, 436 sputum samples from pulmonary TB patients in the National Masan Tuberculosis Hospital were collected for this study. Sputum from a patient was collected two times for the first and second day of sampling time, and these samples were employed for the decontamination process by performing the 4% NaOH and NALC-2% NaOH treatment methods, respectively, for detecting M. tb by an AFB (Acid Fast Bacilli) smear and also by culture in solid Ogawa medium. Results: The NaOH and NALC-NaOH treatment methods did not significantly affect the AFB smear positivity of the sputum samples (33.0% vs 39.0%, respectively, p=0.078). However, the culture positive percents of M. tb in the Ogawa medium treated with NALC-NaOH and NaOH were 39.7% and 28.0%, respectively, which was a significantly different (p=0.0003). This difference in culture was more prominent in the sputum samples that were smear negative (the positive percents with NALC-NaOH and NaOH were 15.8% and 7.2%, respectively, p=0.0017) and scanty (NALC-NaOH and NaOH were 60.8% and 42.9%, respectively, p=0.036), but not for a smear that was 1+ or higher (p>0.05). Conclusion: NALC-NaOH treatment is better than NaOH treatment for the detection of M. tb by culture, but not by smear, and especially when the AFB smear is negative and scanty.

• Clinical and Experimental Pediatrics
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• v.48 no.12
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• pp.1354-1361
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• 2005

Purpose : Rotavirus is an enteric pathogen that affects millions of children globally each year. But no specific therapy is available for the management of rotavirus diarrhea. Due to the clear need to define improved modality for treatment of rotavirus diarrhea, we evaluated the efficacy of antirotavirus IgY in the treatment of infants and children with gastroenteritis. Methods : First, the amount of viral particle in the stools of thirteen patients(seven were given IgY, 6 placebo) infected by rotavirus were evaluated for 3 days with the quantitative RT-PCR method. Second, 36 children with known rotavirus infection identified by ELISA or semi-quantitative RT-PCR were evaluated. We gave 5 g anti-rotavirus egg yolk daily in two equally divided doses for 3 days to two groups(an 18 IgY group and an 18 placebo group), respectively after parenteral consent. Daily vomiting frequency, stool frequency, oral intake and urine output were monitored for 3 days, and electrolyte and blood chemistry were checked at the first and third days. Results : First, in the placebo group, the amount of virus particles increased daily, but in the IgY group it decreased daily. Second, when IgY and placebos were given to children infected with rotavirus, diarrhea on the third day decreased significantly in the IgY group, compared with the placebo group. Conclusion : Treatment with antirotavirus immunoglobulin from immunized chicken's egg resulted in a decrease in the amount of viral particles in stools and diarrhea frequency in children. These results suggest that anti-rotavirus IgY is effective in the treatment of rotavirus gastroenteritis.

• Childhood Kidney Diseases
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• v.14 no.2
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• pp.143-153
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• 2010

Purpose: Recently, massive proteinuria has been observed in some transplant patients after switching cyclosporine A (CsA) to sirolimus. To evaluate the pathogenesis of sirolimus-associated proteinuria, we investigated the early changes in slit diaphragm molecules by various administrative conditions of sirolimus and CsA. Methods: In vitro-Mouse podocytes were incubated with buffer (C), sirolimus ($10\;{\mu}g/mL$) after CsA ($10\;{\mu}g/mL$) (C-S), sirolimus only (S) and CsA and sirolimus simultaneously (C+S) for 12, 24, and 48 hours. In vivo- twenty four SPF female Wistar rats were divided into 4 groups buffer (C), sirolimus after 2 weeks of CsA (C-S), sirolimus only (S) and CsA and sirolimus simultaneously (C+S). All groups were treated by intraperitoneal injection every other day for 4 weeks (CsA: 25 mg/kg, sirolimus: 0.5 mg/kg). The changes in mRNA of slit diaphragm molecules were examined by RT-PCR. Results: The mRNA of nephrin was significantly decreased in group C-S and C+S in vitro. In vivo, the mRNA of nephrin in all groups using sirolimus and the mRNA of podocin in group C-S and C+S were decreased. Microscopically, group C-S and C+S showed small vacuolization and calcification in proximal tubular epithelial cells. Immunohistochemistry using nephrin and podocin antibodies did not show remarkable decrease of staining along the glomerular capillaries. Electron-microscopically, focal fusion of foot processes was seen in group C-S and C+S. Conclusion: This study suggests the decrease of slit diaphragm molecules (nephrin and podocin) in podocyte may be one of the causes of sirolimus associated proteinuria, and podocyte injury by sirolimus may need a primary hit by CsA to develop the proteinuria.

• Neonatal Medicine
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• v.16 no.2
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• pp.197-204
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• 2009

Purpose: The objective of this study was to describe the frequency of hepatobiliary dysfunction (HD) at our hospital and determine the possible risk factors and complications associated with the development of HD in very low birth weight infants (VLBWI) treated with parenteral nutrition (PN). Methods: A retrospective study of VLBWI (n=92) that required PN between 2004 and 2008 in the NICU at the Bucheon St. Marys Hospital of Catholic University was performed. HD was defined by a direct bilirubin (DB) >2 mg and a transaminase of 60 IU/L defined cholestasis and liver injury. Groups I, II, and III were limited to cases of cholestasis, liver injury without cholestasis, and no abnormalities, respectively. The VLBWI were compared to each other. Results: Thirty-six subjects (39.1%) had cholestasis and 51 (55.4%) had liver injury. In addition, 36 (39.1%), 19 (20.7%), and 37 (40.2%) subjects were classified as groups I, II, and III, respectively. The three groups showed significant differences in gestational age, 1- and 5-minute Apgar scores, use of surfactant, duration of parenteral nutrition, frequency of RBC transfusions, bronchopulmonary dysplasia (BPD), and patent ductus arteriosus (PDA) (P<0.05). The multiple regression analysis with cholestasis as the dependent variable, showed a significant correlation with gestational age, use of surfactant, frequency of RBC transfusions, and PDA. Conclusion: Various factors, such as birth weight, gestational age, 1- and 5-minute Apgar scores, use of surfactant for respiratory distress syndrome (RDS), frequency of RBC transfusions, BPD, and PDA may be related to hepatobiliary dysfunction in VLBWI treated with PN.

• Tuberculosis and Respiratory Diseases
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• v.46 no.1
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• pp.44-52
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• 1999

Background : Airway infiltration by inflammatory cells, particularly of eosinophils, is one of the characteristic features of asthma. Several mechanisms for the recruitment of eosinophil is focused on the CD4+ T lymphocyte for the preferential production of Th2-c1erived cytokines. Interleukin-10(IL-10) is identified cytokine with potent antiinflammatory activity. This molecule has been shown to inhibit the release of cytokine from inflammatory cells including Th2 cell, and also to inhibit eosinophil survival. We therefore attempted to determine whether decreased synthesis of IL-10 in the lung of bronchial asthma may contribute to inflammation that is characteristics of this dease. Method: Subjects were patients with bronchial asthma(n=23) and normal controls(n=11). IL-10 produced from peripheral mononuclear cell(PBMC) and in bronchoalveolar lavage(BAL) fluid was measured by ELISA method. Degree of bronchial inflammation was assessed by total cell counts and eosinophil percents in BAL fluid, eosinophil infiltration on bronchial biopsy tissue and $PC_{20}$ for methacholine. Results: The IL-10 level produced by PBMC and in BAL fluid from patient with bronchial asthma were not different with normal controls(respectively, $901.6\pm220.4$ pg/ml, $810.9\pm290.8$ pg/ml for PBMC, $24.5\pm9.5$ pg/mL $30.5\pm13.5$ pg/ml for BAL fluid p>0.05). There were significant negative correlation between IL-10 in BAL fluid and eosinophil percents in BAL fluid or degree of eosinophil infiltration in bronchial biopsy (respectively r=-0.522, r=-0.4486 p<0.05). However there was no difference of IL-10 level according to $PC_{20}$ for methacholine. There were no correlation between IL-10 production by PBMC and peripheral blood eosinophil counts or serum eosinophilic cationic protein levels(respectively r=0.1146, r=0.0769 p>0.05). Conclusion: These observation suggest that IL-10 may participate but not acts the crucial role in regulation of the airway inflammation in bronchial asthma.

• Tuberculosis and Respiratory Diseases
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• v.62 no.1
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• pp.33-42
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• 2007

Background: Heme oxygenase-1 (HO-1) is known to modulates the cellular functions, including cell proliferation and apoptosis. It is known that a high level of HO-1 expression is found in many tumors, and HO-1 plays an important role in rapid tumor growth on account of its antioxidant and antiapoptotic effects. Cisplatin is a widely used anti-cancer agent for the treatment of lung cancer. However, the development of resistance to cisplatin is a major obstacle to its use in clinical treatment. We previously demonstrated that inhibiting HO-1 expression through the transcriptional activation of Nrf2 induces apoptosis in A549 cells. The aim of this study was to determine of the inhibiting HO-1 enhance the chemosensitivity of A549 cells to cisplatin. Materials and Methods: The human lung cancer cell line, A549, was treated cisplatin, and the cell viability was measured by a MTT assay. The change in HO-1, Nrf2, and MAPK expression after the cisplatin treatment was examined by Western blotting. HO-1 inhibition was suppressed by ZnPP, which is a specific pharmacologic inhibitor of HO activity, and small interfering RNA (siRNA). Flow cytometry analysis and Western blot were performed in to determine the level of apoptosis. The level of hydrogen peroxide ($H_2O_2$) generation was monitored fluoimetrically using 2',7'-dichlorofluorescein diacetate. Results: The A549 cells showed more resistance to the cisplatin treatment than the other cell lines examined, whereas cisplatin increased the expression of HO-1 and Nrf2, as well as the phosphorylation of MAPK in a time-dependent fashion. Inhibitors of the MAPK pathway blocked the induction of HO-1 and Nrf2 by the cisplatin treatment in A549 cells. In addition, the cisplatin-treated A549 cells transfected with dither the HO-1 small interfering RNA (siRNA) or ZnPP, specific HO-1 inhibitor, showed in a more significantly decrease in viability than the cisplatin-only-treated group. The combination treatment of ZnPP and cisplatin caused in a marked increase in the ROS generation and a decrease in the HO-1 expression. Conclusion: Cisplatin increases the expression of HO-1, probably through the MAPK-Nrf2 pathway, and the inhibition of HO-1 enhances the chemosensitivity of A549 cells to cisplatin.

• Tuberculosis and Respiratory Diseases
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• v.63 no.6
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• pp.497-506
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• 2007

Background: The present investigation was performed in rats and isolated human neutrophils in order to confirm the presumptive role of the positive feedback loop of cytosolic phospholipase $A_2$ ($cPLA_2$) activation by plateletactivating factor (PAF). Methods: The possible formation of the positive feedback loop of the $cPLA_2$ activation and neutrophilic respiratory burst was investigated in vivo and in vitro by measurement of the parameters denoting acute lung injury. In addition, morphological examinations and electron microscopic cytochemistry were performed for the detection of free radicals in the lung. Results: Five hours after intratracheal instillation of PAF ($5{\mu}g/rat$), the lung leak index, lung myeloperoxidase (MPO) activity, the number of neutrophils and the concentration of cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid were increased by PAF as compared with those of control rats. The NBT assay and cytochrome-c reduction assay revealed an increased neutrophilic respiratory burst in isolated human neutrophils following exposure to PAF. Lung and neutrophilic $cPLA_2$ activity were increased following PAF exposure and exposure to hydrogen peroxide increased $cPLA_2$ activity in the lung. Histologically, inflammatory findings of the lung were observed after PAF treatment. Remarkably, as determined by $CeCl_3$ cytochemical electron microscopy, increased production of hydrogen peroxide was identified in the lung after PAF treatment. Conclusion: PAF mediates acute oxidative lung injury by the activation of $cPLA_2$, which may provoke the generation of free radicals in neutrophils.

• Tuberculosis and Respiratory Diseases
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• v.62 no.1
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• pp.5-10
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• 2007

Background: Korean national guidelines for examining contacts with active pulmonary tuberculosis (TB) are a tuberculin skin test (TST) and chest radiographs. The treatment of a latent TB infection as performed only in those younger than six years of age who test positive for TST. Although there is a high incidence of active TB in young Korean soldiers, the current national guidelines for controlling contacts with active TB in soldiers are insufficient. This study highlights the problems with the Korean guidelines for controlling a TB outbreak in a small military unit. Material and Methods: In December of 2005, there was a tuberculosis outbreak in a military unit with a total of 464 soldiers in Kyung Gi province. The chest radiographs were taken of all the soldiers, and TST were carried out on 408 candidates. Results: In the first screening of the chest radiographs, two active TB patients were detected. By August of 2006, four additional cases were detected, making a total of six cases after the outbreak. All the patients showed active pulmonary TB or TB pleuritis. When the results of TST in the close contacts and non-close contacts were compared, there was a significant difference in the absolute size of the induration($9.70{\pm}7.50mm$ vs. $6.26{\pm}7.02mm$, p<0.001) as well as the ratio of patients showing an induration > 10mm (50.0% vs. 32.0%, p<0.001) and 15mm (33.2% vs. 20.9%, p= 0.005). Conclusion: Although the national guidelines for managing a TB outbreak in a military unit were followed, there were continuous instances of new active TB cases. This highlights the need for new guidelines to prevent the spread of TB.