• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.13-25
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• 1999

Background: Ineffective cell-mediated immune response in human tuberculosis is associated with a depressed Thl cytokine response and reduced production of IFN-$\gamma$. Most persons infected with Mycobacterium tuberculosis are healthy tuberculin reactors with protective immunity, but a minority with ineffective immunity develop extensive pulmonary tuberculosis. The cell-mediated immune response is an important aspect of host resistance to mycobacterial infection and is believed to be tightly regulated by a balance between Th1 cytokines including IFN-$\gamma$, IL-12, IL-18, regulated on activation, normal T cell expressed and secreted (RANTES) and Th2 counterparts such as IL-4, monocyte chemoattractant protein-l (MCP-l). Methods: Proliferation and mRNA expression of IFN-$\gamma$, RANTES and MCP-l by RT-PCR in peripheral blood mononuclear cells (PBMCs) in response to in vitro stimulation with mycobacterial antigens were compared in pulmonary tuberculosis patients with cured and treatment failure and in tuberculin-positive and tuberculin-negative healthy subjects. Results: Defective proliferative responsiveness to aqueous TSP antigen was involved with treatment failure tuberculosis patients. Aqueous TSP antigen-induced IFN-$\gamma$ and RANTES mRNA expression was decreased in treatment failure tuberculosis patients compared with healthy tuberculin reactors and cured tuberculosis patients (23.1 % versus 90.0% for IFN-$\gamma$ and 46.2% versus 70.0% versus 46.2% for RANTES). The frequency of MCP-l mRNA expression to aqueous TSP antigen in treatment failure tuberculosis patients was greater than in healthy tuberculin reactors and cured tuberculosis patients (76.9% versus 40.0%). Conclusion: The increasing expression of MCP-1 mRNA in response to aqueous TSP antigen might be predicted to favor Th1 responses and restricted Th1 responses in treatment failure of pulmonary tuberculosis.

• Journal of Environmental Health Sciences
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• v.37 no.6
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• pp.429-439
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• 2011

Objectives: Ethylene oxide (EtO) is classified as a human carcinogen, but EtO is still widely used to sterilize heat-sensitive materials in hospitals. Employees working around sterilizers are exposed to EtO after sterilization. The aim of the present study was to assess the exposure of EtO level, coupled with occupationally induced micronuclei from hospital workers. The influence of genetic polymorphisms of detoxifying genes (GSTT1 and GSTM1) and DNA repair genes (XRCC1 and XRCC3) on the frequencies of micronuclei in relation to exposure of EtO was also investigated. Methods: The study population was composed of 35 occupationally exposed workers to EtO, 18 student controls and 44 unexposed hospital controls in Korea. Exposure to EtO is measured by passive personal samplers. We analyzed the frequencies of micronuclei by performing cytokinesis-block micronucleus assay (CBMN assay) and GSTM1, GSTT1, XRCC1, and XRCC3 were also genotyped by performing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequencies of micronuclei in EtO exposure group, student controls and hospital controls were $18.00{\pm}7.73$, $10.47{\pm}7.96$ and $13.86{\pm}6.35$ respectively and their differences were statistically significant, but no significant differences according to the level of EtO were observed. There was a dose-response relationship between the frequencies of micronuclei and cumulative dose of EtO, but no significantly differences were observed. We also investigated the influence of genetic polymorphisms (GSTM1, GSTT1, XRCC1, and XRCC3) on the frequencies of micronuclei, but there were no differences in the frequencies of micronuclei by genetic polymorphisms. Conclusions: The frequencies of micronuclei in EtO exposure group was significantly higher than control groups. A dose-response relationship was found between the level of EtO exposure and the frequencies of micronuclei, but no statistically differences were observed. We also found that the frequencies of micronuclei were increased according to cumulative EtO level. There was no association of the genetic GSTM1, GSTT1, XRCC1, and XRCC3 state with the frequency of micronuclei induced by EtO exposure.

• Journal of Nutrition and Health
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• v.48 no.1
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• pp.9-18
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• 2015

Purpose: Poncirus trifoliata has been reported to have anti-inflammatory, antioxidant, and immune activities. However, its anti-obesity activity and the mechanism by which the water extract of dried, immature fruit of Poncirus trifoliata (PF-W) acts are not clear. This study suggests a potential mechanism associated with the anti-obesity activity of PF-W. Methods: We measured the effect of PF-W on lipoprotein lipase (LPL) regulation using enzyme-linked immunosorbent assay (ELISA) and an activity assay. The LPL regulation mechanism was examined by reverse transcription polymerase chain reaction (RT-PCR) to measure the mRNA expression of biomarkers related to protein transport and by western blot for analysis of the protein expression of the transcription factor CCAAT-enhancer-binding protein ($C/EBP{\beta}$). Results: The total polyphenol and flavonoid content of PF-W was $52.15{\pm}4.02$ and $6.56{\pm}0.47mg/g$, respectively. PF-W treatment decreased LPL content in media to $58{\pm}5%$ of that in control adipocyte media, and increased LPL content to $117{\pm}3.5%$ of that in control adipocytes, but did not affect the mRNA expression of LPL. PF-W also increased the mRNA expression of sortilin-related receptor (SorLA), a receptor that induces endocytosis and intracellular trafficking of LPL, in a concentration- and time-dependent manner. Finally, cell fractionation revealed that PF-W treatment induced the expression of $C/EBP{\beta}$, a SorLA transcription factor, in the nuclei of 3T3-L1 adipocytes. Conclusion: The LPL secretion and activity assay showed PF-W to be an LPL secretion inhibitor, and these results suggest the potential mechanism of PF-W involving inhibition of LPL secretion through $C/EBP{\beta}$-mediated induction of SorLA expression.

• Journal of Nutrition and Health
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• v.51 no.4
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• pp.275-286
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• 2018

Purpose: Our previous study demonstrated that persimmon (Diospyros kaki Thumb.) at different stages of ripening provided different protective effects against high-fat/cholesterol diet (HFD)-induced dyslipidemia in rats. In this study, we compared the metabolites profile and gene expressions related to triglyceride (TG)/cholesterol metabolism in vitro and in vivo after treating with persimmon water extracts (PWE) or tannin-enriched persimmon concentrate (TEP). Methods: Primary and secondary metabolites in test materials were determined by GC-TOF/MS, UHPLC-LTQ-ESI-IT-MS/MS, and UPLC-Q-TOF-MS. The expression of genes related to TG and cholesterol metabolism were determined by RT-PCR both in HepG2 cells stimulated by oleic acid/palmitic acid and in liver tissues obtained from Wistar rats fed with HFD and PWE at 0, 150, 300, and 600 mg/d (experiment I) or TEP at 0, 7, 14, and 28 mg/d (experiment II) by oral gavage for 9 weeks. Results: PLS-DA analysis and heatmap analysis demonstrated significantly differential profiling of metabolites of PWE and TEP according to processing of persimmon powder. In vitro, TEP showed similar hypolipidemic effects as PWE, but significantly enhanced hypocholesterolemic effects compared to PWE in sterol regulatory element-binding protein 2 (SREBP2), HMG-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesterol $7{\alpha}-hydroxylase$ (CYP7A1), and low density lipoprotein receptor (LDLR) gene expression. Consistently, TEP and PWE showed similar hypolipidemic capacity in vivo, but significantly enhanced hypocholesterolemic capacity in terms of SREBP2, HMGCR, and bile salt export pump (BSEP) gene expression. Conclusion: These results suggest that column extraction after hot water extraction may be a good strategy to enhance tannins and long-chain fatty acid amides, which might cause stimulation of hypocholesterolemic actions through downregulation of cholesterol biosynthesis gene expression and upregulation of LDL receptor gene expression.

• Clinical and Experimental Pediatrics
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• v.52 no.6
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• pp.680-688
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• 2009

Purpose : Cysteinyl leukotrienes are important proinflammatory mediators in asthma. Recently, it was suggested that a promoter polymorphism in the genes encoding for leukotriene C4 synthase (LTC4S), a key enzyme in the leukotriene synthetic pathway, and cysteinyl leukotriene receptor 1 (CysLTR1) might be associated with aspirin-intolerant asthma. We investigated whether polymorphisms in LTC4S and CysLTR1 genes or their interactions were associated with the asthma phenotype, lung function, or bronchial hyperreactivity (BHR) in Korean children. Methods : A total of 856 asthmatic children and 254 non-asthmatic controls were enrolled; a skin prick test, lung function test and bronchial provocation test were performed. Of those enrolled, 395 children underwent exercise challenge tests. The LTC4S A(-444)C and CysLTR1 T(＋927)C were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. Results : Of those enrolled, 699 children were classified as having atopic asthma and 277 children, as having exercise-induced asthma (EIA). LTC4S and CysLTR1 polymorphisms were not associated with atopic asthma, EIA, or asthma per se. Lung function and BHR were not significantly different between the wild type (AA or TT) and the variant (AC＋CC or TC＋CC) genotypes in asthmatics, atopic asthmatics, and EIA (＋) asthmatics, while total eosinophil counts were higher in the variant type of LTC4S than in the wild type in atopic asthmatics. There were no associations between the gene-gene interactions of LTC4S and CysLTR1 genotypes and the asthma phenotypes. Conclusion : LTC4S A(-444)C and CysLTR1 T(＋927)C polymorphisms and their gene-gene interactions are not associated with asthma phenotype, lung function, or BHR in Korean children.

• Clinical and Experimental Pediatrics
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• v.52 no.8
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• pp.904-909
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• 2009

Purpose : The differential diagnosis for a pulmonary nodule is intriguing in cancer patients. Metastasis might be a preferential diagnosis, and yet possibilities of other medical conditions still exist. Pulmonary tuberculosis should be enlisted in the differential diagnosis for a pulmonary nodule in cancer patients in Korea. This study was aimed at analyzing the incidence and clinical features of pulmonary tuberculosis that were misdiagnosed as pulmonary metastasis during radiologic follow-up in pediatric cancer patients. Methods : We retrospectively studied 422 cancer patients less than 18 years old in the Korea Cancer Center Hospital from January 2001 to June 2007. We collected episodes of lung metastasis of primary tumor and tuberculosis during treatment or follow-up, and analyzed medical records. Results : There were 5 cases of tuberculosis confirmed after surgery which were initially regarded as cancer. Two patients had respiratory symptoms such as cough and sputum but the other 3 patients did not. One patient had a family history of tuberculosis. Acid-fast M. tuberculosis was found in one case upon tissue specimen analysis. Two cases were Mantoux positive and the sputum examination was negative in all cases. The polymerase chain reaction for tuberculosis on a pathologic specimen was used to differentiate M. tuberculosis from non-tuberculosis mycobacterium (NTM). It was positive in one case. Lung lesions in one case showed a concurrence of tuberculosis along with lung metastasis. One of these patients died after cancer recurrence. Conclusion : It is necessary to consider the possibility of tuberculosis when a lung mass is newly detected during treatment or follow-up in patients with childhood cancer.

• Clinical and Experimental Pediatrics
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• v.52 no.12
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• pp.1337-1347
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• 2009

Purpose:Taurine (2-aminoethanesulfonic acid) is a simple sulfur-containing amino acid. It is abundantly present in tissues such as brain, retina, heart, and skeletal muscles. Current studies have demonstrated the neuroprotective effects of taurine, but limited data are available for such effects during neonatal period. The aim of this study was to determine whether taurine could reduce hypoxic-ischemic (HI) cerebral injury via anti-apoptosis mechanism. Methods:Embryonic cortical neurons isolated from Sprague-Dawley (SD) rats at 18 days gestation were cultured in vitro. The cells were divided into hypoxia group, taurine-treated group before hypoxic insult, and taurine-treated group after HI insult. In the in vivo model, left carotid artery ligation was performed in 7-day-old SD rat pups. The pups were exposed to hypoxia, administered an injection of 30 mg/kg of taurine, and killed at 1 day, 3 days, 1 week, 2 weeks, and 4 weeks after the hypoxic insult. We compared the expressions of Bcl-2, Bax, and caspase-3 among the 3 groups by using real- time polymerase chain reaction (PCR) and western blotting. Results:The cells in the taurine-treated group before hypoxic insult, although similar in appearance to those in the normoxia group, were lesser in number. In the taurine-treated group, Bcl-2 expression increased, whereas Bax and caspase-3 expressions reduced. Conclusion:Taurine exerts neuroprotective effects onperinatal HI brain injury due to its anti-apoptotic effect. The neuroprotective effect was maximal at 1-2 weeks after the hypoxic injury.

• Clinical and Experimental Pediatrics
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• v.52 no.6
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• pp.667-673
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• 2009

Purpose : Toll-like receptor 2 (TLR2) is critical in the immune response to mycobacterial infections. The purpose of this study was to analyze TLR2 surface expressions and TLR2-mediated tumor necrosis factor-alpha ($TNF-{\alpha}$) and interleukin-6 (IL-6) production in patients with BCG vaccine-associated suppurative lymphadenitis. Methods : Peripheral monocytes were separated from 16 patients with BCG vaccine-associated suppurative lymphadenitis and 10 healthy controls using a magnet cell isolation kit. Monocytes ($1{\times}10^6$ cells/well) were incubated with a constant amount of $Pam_3CSK_4$ ($100{\mu}g/mL$) for 24 hours. TLR2 surface expression on monocytes was analyzed by FACS analysis and TLR-2 mRNA expression was determined by RT-PCR. TLR2-mediated $TNF-{\alpha}$ and IL-6 production were measured by ELISA. Results : In patients with BCG vaccine-associated suppurative lymphadenitis, low TLR2 expression on monocytes ($3.39{\pm}$1.2% versus $4.64{\pm}2.6%$) together with significantly lower TLR2 mRNA expression than in the healthy controls was seen after $Pam_3CSK_4$ stimulation. TLR2-mediated $TNF-{\alpha}$ and IL-6 production in patients with BCG vaccine-associated suppurative lymphadenitis ($TNF-{\alpha}$, $775.5{\pm}60.8pg/mL$; IL-6, $4,645.8{\pm}583.9pg/mL$) were also lesser than that in healthy controls ($TNF-{\alpha}$, $1,098.5{\pm}94.3pg/mL$; IL-6, $6,696.3{\pm}544.3pg/mL$). Conclusion : These findings suggest that low TLR2 expression on monocytes might be associated with increased susceptibility to BCG vaccine-associated suppurative lymphadenitis.

• Clinical and Experimental Pediatrics
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• v.51 no.10
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• pp.1102-1111
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• 2008

Purpose : Resveratrol, extracted from red wine and grapes, has an anti-cancer effect, an antiinflammatory effect, and an antioxidative effect mainly in heart disease and also has neuroprotective effects in the adult animal model. No studies for neuroprotective effects during the neonatal periods have been reported. Therefore, we studied the neuroprotective effect of resveratrol on hypoxic-ischemic brain damage in neonatal rats via anti-apoptosis. Methods : Embryonic cortical neuronal cell culture of rat brain was performed using pregnant Sprague-Dawley (SD) rats at 18 days of gestation (E18) for the in vitro approach. We injured the cells with hypoxia and administered resveratrol (1, 10, and $30{\mu}g/mL$) to the cells at 30 minutes before hypoxic insults. In addition, unilateral carotid artery ligation with hypoxia was induced in 7-day-old neonatal rats for the in vivo approach. We injected resveratrol (30 mg/kg) intraperitoneally into animal models. Real-time PCR and Western blotting were performed to identify the neuroprotective effects of resveratrol through anti-apoptosis. Results : In the in vitro approach of hypoxia, the expression of Bax, caspase-3, and the ratio of Bax/Bcl-2, indicators of the level of apoptosis, were significantly increased in the hypoxia group compared to the normoxia group. In the case of the resveratrol-treated group, expression was significantly decreased compared to the hypoxia group. And the results in the in vivo approach were the same as in the in vitro approach. Conclusion : The present study demonstrates that resveratrol plays neuroprotective role in hypoxic-ischemic brain damage during neonatal periods through the mechanism of anti-apoptosis.

• Korean Journal of Poultry Science
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• v.36 no.3
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• pp.207-213
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• 2009

Adenylosuccinate lyase (ADSL) deficiency is a disease of purine metabolism which affects patients both biochemicall and behaviorally. An obstacle of this purine nucleotide cycle(PNC) can be caused brain functional disorder and growth disorder. So ADSL deficiency, which is associated with sever mental retardation, autistic features and energy metabolism. This study was performed to identify SNP on ADSL gene in chicken. The nucleotides were observed as T to C ($7724^{th}$ nucleotide), C to T ($7732^{nd}$ nucleotide), G to T ($10108^{th}$ nucleotide), A to T ($10356^{th}$ nucleotide), G to A($10375^{th}$ nucleotide), A to C ($10402^{nd}$ nucleotide), A to T ($12716^{th}$ nucleotide), T to A ($12717^{th}$ nucleotide), C to T ($15491^{st}$ nucleotide), C to T ($15542^{nd}$ nucleotide) and C to T ($15550^{th}$ nucleotide). The nucleotide substitutions at $15542^{nd}$ and $15550^{th}$ (GeneBank accession no. AY665559) were found as missense mutation (alanine$\rightarrow$valine, proline$\rightarrow$serine, respectively). This study will be useful for farther researches for identifying association between these SNPs and energy metabolism in chicken. The C15550T SNP showed three genotypes, CC, CT, TT by digestion with the genotype TT had significantly faster the first lay day (150.0) than CT (162.0, P<0.05) and genotype TT (150.0, P<0.05) had significantly higher the egg production rate than CT (172.4, P<0.05). According to result of this study, a C15550T was found to have a significantly effect first lay day and mean egg production. It will be possible to use SNP marker on selecting chicken to improve important economic traits, which is the first lay day and mean egg production.