• Journal of Radiation Protection and Research
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• v.28 no.3
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• pp.233-237
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• 2003

It has been known that ATM plays a central role in response of cells to ionizing radiation by enhancing DNA repair. We have investigated the feasibility of increasing radiosensitivity of tumor cells with the use of ATM inhibitors such as caffeine, pentoxifylline and wortmannin. Human colorectal cancer RKO.C cells and RKO-ATM cells (RKO cells overexpressing ATM) were used in the present study. The clonogenic cell survival in vitro indicated that RKO-ATM cells were markdely radioresistant than RKO.C cells. Treatment with 3 mM of caffeine significantly increased the radiosensitivity of cells, particulary the RKO-ATM cells, so that the radiosensitivity of RKO.C cells and RKO-ATM cells were almost similar. The radiation induced G2/M arrest in RKO-ATM cells was noticeably longer than that in RKO.C cells and caffeine treatment significantly reduced the length of the radiation induced G2/M arrest in both RKO.C and RKO-ATM cells. Pentoxifylline and wortmannin were also less effective than caffeine to radiosensitize RKO.C or RKO-ATM cells. However, wortmannin was more effective than caffeine against human lung adenocarcinoma A549 cells indicating the efficacy of ATM inhibitor to increase radiosensitivity is cell line dependent. For in vivo study, RKO.C cells were injected s.c. into the hind-leg of BALB/C-nuslc nude mice, and allowed to grow to 130mm3 tumor. The mice were i.p. injected with caffeine solution or saline and the tumors irradiated with 10 Gy of X-rays. The radiation induced growth delay was markedly increased by 1-2 mg/g of caffeine. It was concluded that caffeine increases radiosensitivity of tumor cells by inhibiting ATM kinase function, thereby inhibiting DNA repair, that occurs during the G2/M arrest after radiation.

• Tuberculosis and Respiratory Diseases
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• v.72 no.3
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• pp.302-309
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• 2012

Background: Korean regression models for spirometric reference values are different from those of Americans. Using spirometry results of Korean adults, goodness-of-fits of the Korean and the USA Caucasian regression models for forced vital capacity (FVC) and forced expiratory volume in one second ($FEV_1$) were compared. Methods: The number of study participants was 2,360 (1,124 males and 1,236 females). Spirometry was performed under the guidelines of the American Thoracic Society and the European Respiratory Society. After excluding unsuitable participants, spirometric data for 729 individuals (105 males and 624 females) was included in the statistical analysis. The estimated FVC and $FEV_1$ values were compared with those measured. Goodness-of-fits for Korean and USA Caucasian models were compared using an F-test. Results: In males, the expected values of FVC and $FEV_1$ using the Korean model were 12.5% and 5.7% greater than those measured, respectively. The corresponding values for the USA Caucasian model were 3.5% and 0.6%. In females, the difference in FVC and $FEV_1$ were 13.5% and 7.7% for the Korean model, and 6.3% and 0.4% for the USA model, respectively. Goodness-of-fit for the Korean model regarding FVC was not good to the study population, but the Korean regression model for $FEV_1$, and the USA Caucasian models for FVC and $FEV_1$ showed good fits to the measured data. Conclusion: These results suggest that the USA Caucasian model correlates better to the measured data than the Korean model. Using reference values derived from the Korean model can lead to an overestimation regarding the prevalence of abnormal lung function.

• Tuberculosis and Respiratory Diseases
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• v.76 no.5
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• pp.226-232
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• 2014

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and results from environmental factors and genetic factors. Although cigarette smoking is a major risk factor, other environmental exposures can influence COPD. The purpose of this study is to investigate the clinical characteristics of COPD according to the history of environmental exposure. Methods: The study population comprised of 347 subjects with COPD who were recruited from the pulmonary clinics of 14 hospitals within the Korean Obstructive Lung Disease Study Group. We classified environmental exposures according to history of living near factory, and direct exposure history to firewood or briquette. According to living environmental exposures, we compared the frequency of respiratory symptoms, pulmonary function, quality of life, exercise capacity, and computed tomography phenotypes. Results: Thirty-one subjects (8.9%) had history of living near factory, 271 (78.3%) had exposure history to briquette, and 184 (53.3%) had exposure history to firewood. Patients with history of living near a factory had a significantly longer duration of sputum, while patients with exposure to firewood tended to have lower forced expiratory volume in one second, and patients with exposure to briquette tended to have lower six minute walk distance. Conclusion: COPD subjects with the history of living near factory had more frequent respiratory symptoms such as sputum. Our data suggest that environmental exposure may influence clinical phenotype of COPD.

• Toxicological Research
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• v.25 no.3
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• pp.140-146
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• 2009

This study was performed to evaluate the toxicity of cadmium selenide for a period of 28 days in Sprague-Dawley rats. Each of 10 healthy male and females rats per group received daily oral administration for 28-day period at dosage levels 30, 300 and 1,000 mg/kg of body weight. Mortality and clinical signs were checked, and body weight, water intake and food consumption were also recorded weekly. There were no dose-related changes in food consumption or urine volume. All animals survived to the end of study with no clinical signs or differences in body weight gain observed when compared with the control group. At the end of study, all animals including control group, were subjected to necropsy. Blood samples were collected for hematology tests including coagulation time and biochemistry analysis. Blood coagulation time and relative organ weight were unaffected by all received doses. White Blood Cell (WBC) counts significantly increased in the 300 mg/kg administered male animal group when compared to the control. Monocyte (MO) value were also increased significantly in both 300 and 1,000 mg/kg male animal group. However, Mean Corpuscular Volume (MCV) were significantly decreased compared with the control in the 1,000 mg/kg dose groups for male and female animals. Mean Corpuscular Hemoglobin (MCH) decreased significantly for female in the 300 and 1,000 mg/kg group compared to the control. Blood biochemical values of Inorganic phosphorus (IP) were significantly increased in both the 300 and 1,000 mg/kg dose groups in male animals when compared to the control. Creatinine (CRE) levels indicated significant increase in kidney function for the female, 30 mg/kg dose group when compared with control. There was a significant decrease in thymus absolute organ weight in the female, 1,000 mg/kg dose group when compared with control. Histopathological findings revealed no evidence of injury related to cadmium selenide except for one case of focal hepatic inflammation in the high dose (1,000 mg/kg) group. One case of lung inflammation was also seen in the control group. Basis on these result, the No Observable Adverse Effect Level (NOAEL) of cadmium selenide was determined to be more than 1,000 mg/kg/day for male and female rats under conditions in this study.

• The Journal of the Society of Korean Medicine Diagnostics
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• v.15 no.2
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• pp.175-190
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• 2011

Objectives: Even though there has been no consensus on the concept of viscera organ between the oriental and western medicine, we tried to investigate the correlation between clinical biomarkers of five Jang and chronological age and develop the models for predicting five Jang biological ages by statistical analysis. Methods: We obtained data from about 120,000 subjects who visited health promotion centers for health promotion and disease prevention from January 2004 to June 2009. Participants were included if they were over 20 years old, and excluded if reported to have cardiovascular disease or other serious medical illness such as cancer, malignant hypertension, uncontrolled diabetes, cardiopulmonary insufficiency, liver disease, pancreatic disease or renal disease. Among the clinical biomarkers obtained, we selected the biomarkers which were associated with the function of 5 Jang in previous studies, or showed statistically significant correlation with age. Multiple regression models were used for building prediction models of biological age after adjusting for potential confounders for men and women, respectively. Pearson correlation coefficient was calculated to examine the linear relationship between age and various biomarkers, and multiple regression analysis was used for building the prediction models of five Jang biological ages for men and women, respectively. All statistical data analysis was performed by using SPSS Version 12.0 software and statistical significance was obtained if p<0.05. Results: For males, the best models were developed using 12, 2, 8, 3, and 4 biomarkers for predicting biological ages of heart, lung, liver, pancreas, and kidney, respectively (R2 = 0.57, 0.43, 0.11, 0.24, and 0.93, respectively). Similar to males, for the females, 10, 2, 8, 3, and 4 biomarkers were selected as the models respectively (R2 = 0.76, 0.44, 0.14, 0.38, and 0.89, respectively). Conclusions: As we have developed for the first time the models for predicting five Jang biological ages with common clinical biomarkers, it is expected that these models may be used as clinical supplementary tools in the evaluation of aging status and functional decline of five Jang according to age in health promotion centers and private clinics. At the same time, it is considered that the use as objective tools to evaluate aging status and functional decline of each Jang.

• Clinical and Experimental Pediatrics
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• v.50 no.9
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• pp.862-867
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• 2007

Purpose : The impulse oscillometry (IOS) is applicable to young children because it requires minimal cooperation and a non-invasive method to measure the mechanics of respiratory system. This study aimed to develop the reference values in school-aged children in Korea, using IOS which is a modification of forced oscillation technique (FOT). Methods : Measurements were performed in 92 previously untrained healthy children, aged 7 to 12 years old, using IOS. We analyzed the relationships between the data about their age, height, weight, body surface area (BSA), body mass index (BMI) and the result of IOS using the linear regression test. Results : The success rate of IOS was 92.4%. Stepwise multiple regression of resistance of respiratory system (Rrs) and reactance of respiratory system (Xrs) in natural form for age, height, weight, BSA, BMI showed that height was the most significant predictor and altogether of 5 variables explained the Rrs and Xrs most. Our regression equations at multiple frequencys were comparable to published reference values, especially about the Rrs obtained at 5 Hz. Conclusion : IOS is a feasible method to measure the respiratory resistance in untrained children. We got the reference values using IOS and it seems to be useful to diagnose a variety of respiratory diseases.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.2
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• pp.288-298
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• 2016

Resveratrol acts as a free radical scavenger and a potent antioxidant in the inhibition of numerous reactive oxygen species (ROS). The function of resveratrol and resveratrol-loaded nanoparticles in protecting human lung cancer cells (A549) against hydrogen peroxide was investigated in this study. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay was performed to evaluate the antioxidant properties. Resveratrol had substantially high antioxidant capacity (trolox equivalent antioxidant capacity value) compared to trolox and vitamin E since the concentration of resveratrol was more than $50{\mu}M$. Nanoparticles prepared from ${\beta}$-lactoglobulin (${\beta}$-lg) were successfully developed. The ${\beta}$-lg nanoparticle showed 60 to 146 nm diameter in size with negatively charged surface. Non-cytotoxicity was observed in Caco-2 cells treated with ${\beta}$-lg nanoparticles. Fluorescein isothiocynate-conjugated ${\beta}$-lg nanoparticles were identified into the cell membrane of Caco-2 cells, indicating that nanoparticles can be used as a delivery system. Hydrogen peroxide caused accumulation of ROS in a dose- and time-dependent manner. Resveratrol-loaded nanoparticles restored $H_2O_2$-induced ROS levels by induction of cellular uptake of resveratrol in A549 cells. Furthermore, resveratrol activated nuclear factor erythroid 2-related factor 2-Kelch ECH associating protein 1 (Nrf2-Keap1) signaling in A549 cells, thereby accumulation of Nrf2 abundance, as demonstrated by western blotting approach. Overall, these results may have implications for improvement of oxidative stress in treatment with nanoparticles as a biodegradable and non-toxic delivery carrier of bioactive compounds.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.3
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• pp.398-407
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• 2020

Objective: The Yip1 domain family (YIPF) proteins were proposed to function in endoplasmic reticulum (ER) to Golgi transport and maintenance of the morphology of the Golgi, which were homologues of yeast Yip1p and Yif1p. YIPF3, the member 3 of YIPF family was a homolog of Yif1p. The aim of present study was to investigate the expression and regulation mechanism of porcine YIPF3. Methods: Quantitative realtime polymerase chain reaction (qPCR) was used to analyze porcine YIPF3 mRNA expression pattern in different tissues and pig kidney epithelial (PK15) cells stimulated by polyinosine-polycytidylic acid (poly [I:C]). Site-directed mutations combined with dual luciferase reporter assays and electrophoretic mobility shift assay (EMSA) were employed to reveal transcription regulation mechanism of porcine YIPF3. Results: Results showed that the mRNA of porcine YIPF3 (pYIPF3) was widely expressed with the highest levels in lymph and lung followed by spleen and liver, while weak in heart and skeletal muscle. Subcellular localization results indicated that it expressed in Golgi apparatus and plasma membranes. Upon stimulation with poly (I:C), the level of this gene was dramatically up-regulated in a time- and concentration-dependent manner. pYIPF3 core promoter region harbored three cis-acting elements which were bound by ETS proto-oncogene 2 (ETS2), zinc finger and BTB domain containing 4 (ZBTB4), and zinc finger and BTB domain containing 14 (ZBTB14), respectively. In which, ETS2 and ZBTB4 both promoted pYIPF3 transcription activity while ZBTB14 inhibited it, and these three transcription factors all played important regulation roles in tumorigenesis and apoptosis. Conclusion: The pYIPF3 mRNA expression was regulated by ETS2, ZBTB4, and ZBTB14, and its higher expression in immune organs might contribute to enhancing ER to Golgi transport of proteins, thus adapting to the immune response.

• IMMUNE NETWORK
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• v.3 no.3
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• pp.211-218
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• 2003

Background: Vitamin C is an essential nutrient, taken as a daily supplement by many people. Recently, high-dose vitamin C is considered as a therapeutic regimen in some clinical situations. Until now, few studies have been done with the effects of high-dose vitamin C on the immune response. Methods: In this experiment, the effects of high-dose vitamin C on cell-mediated immune response in immunologically competent mice were evaluated. After intraperitoneal injection of 2.5, 5, or 10 mg/day of vitamin C for 10 days, delayed type hypersensitivity (DTH) was provoked against DNFB in the pinnae as a model for cell-mediated immune response. Severity of DTH reaction was evaluated as the thickness of pinnae, and the vitamin C levels were measured in the serum, liver, kidney, lung, pinnae, and splenocytes. Results: After challenge, the thickness increased at its peak on the $2^{nd}$ day in all groups. On the first day, the pinnae were thicker in the injected groups than in the control. On the contrary, the increment of the pinnae thickness was attenuated and the number of cells infiltrated in the site of DTH decreased proportionately to the amount of vitamin C administered from the second day on. With vitamin C exogenously given, the serum level peaked at 30 min after injection, and returned abruptly to its basal level without accumulation. However, it accumulated in the liver, kidney, and especially in the pinnae inflamed and splenopcytes, proportionately to the amount administered. Conclusion: Based on these results, it is suggested that, in one hand, exogenously administered high-dose vitamin C accumulated in the splenocytes and presumably changed the function of them resulting in the augmented cell-mediated immune response, as was revealed in the first day of DTH reaction. On the other hand, it seems likely that the vitamin C also showed anti-inflammatory effects.

• Tuberculosis and Respiratory Diseases
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• v.67 no.2
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• pp.113-120
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• 2009

Background: Reactive oxygen species (ROS) by oxidative stress may play an important role in the pathogenesis of various chronic diseases such as diabetes mellitus, obesity, hyperlipidemia, hypertension and malignancy that are linked to metabolic syndrome. Oxidative stress has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We examined the relationship between IPF and presenting factors associated with metabolic disorders. Methods: One hundred fourteen patients who met the current consensus of IPF definition were enrolled from March 2000 to April 2006 in Gil Hospital and Samsung Medical Center in Korea. One hundred thirty-four control subjects without pulmonary diseases were selected from subjects who visited Gil hospital for routine medical examinations, including low-dose chest computed tomography from January 2002 to July 2006. Retrospectively, we analyzed the clinical characteristics, the results of blood examinations, and lung function tests from medical records of both groups. Results: IPF patients and control subjects differed in the prevalence of diabetes mellitus as assessed by univariate analysis. Multivariate analysis demonstrated that diabetes mellitus and obesity were associated with IPF. The adjusted odds ratios for diabetes mellitus were 2.733 (95% confidence interval [CI], 1.282~5.827) and 2.001 (95% [CI], 1.063~3.766) for obesity. The remaining factors tested showed no differences between the patient group and the control. Conclusion: Diabetes mellitus and obesity may be associated with IPF development.