• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.871-888
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• 1997

Background : It is now thought that the earliest manifestation of idiopathic pulmonary fibrosis is alveolitis, that is, an accumulation of inflammatory and immune effector cells within alveolar walls and spaces. Inflammatory cells including alveolar macrophages and resident normal pulmonary tissue cells participate through the release of many variable mediators such as inflammatory growth factors and cytokines, which contribute to tissue damage and finally cause chronic pulmonary inflammation and fibrosis. This study was performed to investigate the source and distribution pattern of transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), platelet derived growth factor(PDGF), basic fibroblast growth factor(bFGF), interleukin 1(IL-1), interleukin 6(IL-6), tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and the role of these mediators on bleomycin(BLM)-induced pulmonary injury and fibrosis in rats. Method : Wistar rats were divided into three groups(control group, BLM treated group, BLM and vitamine E treated group). Animals were sacrificed periodically at 1, 2, 3, 4, 5, 7, 14, 21, 28 days after saline or BLM administration. The effects were compared to the results of bronchoalveolar lavage fluid analysis, light microscopic findings, immunohistochemical stains for six different mediators(TGF-${\beta}_1$, PDGF, bFGF, IL-1, IL-6 and TNF-$\alpha$) and mRNA in situ hybridization for TGF-${\beta}_1$. Results : IL-1 and IL-6 are maximally expressed at postbleomycin 1~7th day which are mainly produced by neutrophils and bronchiolar epithelium. It is thought that they induce recruitment of inflammatory cells at the injury site. The expression of IL-1 and IL-6 at the bronchiolar epithelium within 7th day is an indirect evidence of contribution of bronchiolar epithelial cells to promote and maintain the inflammatory and immune responses adjacent to the airways. TNF-$\alpha$ is mainly produced by neutrophils and bronchiolar epithelial cells during 1~5th day, alveolar macrophages during 7~28th day. At the earlier period, TNF-$\alpha$ causes recruitment of inflammatory cells at the injury site and later stimulates pulmonary fibrosis. The main secreting cells of TGF-${\beta}_1$ are alveolar macrophages and bronchiolar epithelium and the target is pulmonary fibroblasts and extracellular matrix. TGF-${\beta}_1$ and PDGF stimulate proliferation of pulmonary fibroblasts and TGF-${\beta}_1$ and bFGF incite the fibroblasts to produce extracellular matrix. The vitamine E and BLM treated group shows few positive cells(p<0.05). Conclusion : After endothelial and epithelial injury, the neutrophils and bronchiolar epithelium secrete IL-1, IL-6, TNF-$\alpha$ which induce infiltration of many neutrophils. It is thought that variable enzymes and $O_2$ radicals released by these neutrophils cause destruction of normal lung architecture and progression of pulmonary fibrosis. At the 7~28th day, TGF-${\beta}_1$, PDGF, bFGF, TNF-$\alpha$ secreted by alveolar macrophages sting pulmonary fibroblasts into proliferating with increased production of extracellular matrix and finally, they make progression of pulmonary fibrosis. TNF-$\alpha$ compares quite important with TGF-${\beta}_1$ to cause pulmonary fibrosis. Vitamine E seems to decrease the extent of BLM induced pulmonary fibrosis.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.600-612
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• 1996

Background : Recent studies deported that untreated patients with obstructive sleep apnea syndrome had high long-term mortality rates, and cardiovascular complications of these patients clad a major effect on mortality. Several data indicates that obstructive sheep apnea syndrome contributes to the development of diurnal systemic hypertension. But the pathophysiological mechanism of the development of systemic hypertension in these patients is still uncertain. This study was performed to evaluate the possible role of sympathetic nervous system activity for the development of systemic hypertension in patients with obstructive sleep apnea syndrome. Method : 35 patients with obstructive sleep apnea syndrome(OSAS) and 13 Control subjects(control) were included in this study. 21 patients of OSAS were normotensives(OSAS-NBP), and 14 patients of OSAS were hypertensives(OSAS-HBP). Full night polysomnography was undertaken to all subjects. We measured plasma norepinephrine(NE) and epinephrine(EP) concentrations during waking and sleep, using high performance liquid chromatography, in all patients and control subjects. Results : In OSAS, OSAS-NBP and control, plasma NE and EP concentrations during sleep were lowed than during waking(p<0.01). But, in OSAS-HBP, these was no difference between during waking and sleep. Plasma NE concentrations during sleep of OSAS, OSAS-NBP and OSAS-HBP were higher than Control(p<0.05). In OSAS-HBP, daytime systolic blood pressure correlated with plasma NE concentration during sleep(r=0.7415, p<0.01), arid correlated inversely with mean arterial oxygen saturation(r=-0.6465, p<0.05) or arterial oxygen saturation nadir(r=-0.6) 14, p<0.05) during sleep. Conclusion : The sympathetic activity during sleep of obstructive sleep apnea syndrome patients was higher than control subjects. In obstructive sleep apnea syndrome patients with systemic hypertension, there was no diurnal variation of sympathetic activity, and there was correlation between daytime systolic blood pressure and sympathetic activity during sleep. These data suggests that chronic hyperactivity of sympathetic nervous system may contribute to the development of diurnal systemic hypertension in patients with obstructive sleep apnea syndrome.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.2
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• pp.183-195
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• 2011

This study was conducted to investigate dietary behavior patterns of high school students. As for regularity of meal, female students were significantly more regular than those of the male students in a day. They answered 'between 4th and 6th grades in elementary school' as 'the time for formation about number of meal intake'. As for a highly influential meal, males were higher answered 'lunch (41.0%)' while females were higher answered 'breakfast (39.8%)'. About 'number of meals per day by the grade', they ate 3 times per day mostly. As for the time for formation about number of meal intake: 'before 4th to 6th in elementary school'> 'before elementary school'. In the result of regularity of meal and general characteristics, a family of 5 was higher in regularity and those with pocket money showed lower regularity in meal. As for the person who prepares a meal, mothers prepared meals regularly. Also, higher parents age and education level resulted in more regularity in meals. In number of meals per day and general characteristics, they were eating 3 times; moreover, this trend was evident as parents' age and education level and the household income was higher. Students answered generally regularity in meal in family where parents' jobs were administrative assistant (father job (56.9%)) and housewife (mother (56.9%). In the formation time of meal intake number and general characteristics, they answered order 'middle school'> 'before elementary school'. A highly influential meal, they answered as the highest 'lunch' (37.6%). This study may provide information on dietary behavior of high school students, suggesting that nutrition education or counseling can improve food habits and develop positive behavior.

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.519-529
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• 2002

Background : The therapeutic effects of surfactants on acute lung injury derive not only from their recruiting action on collapsed alveoli but also from their anti-inflammatory action in the alveolar sapce. This study evaluated the anti-inflammatory action of a surfactant in an acute lung injury model of rats by neutrophils were recollected from the BAL fluid and the NF-${\kappa}B$ activity of the neutrophilic nuclear protein was evaluated. Methods : Male Sprague-Dawley rats weighing approximately 300 gram were divided into 3 groups, which consisted of 6 rats respectively. In the control group, normal saline(3ml/kg) was instilled into the trachea twice with 30 minute interval. In two other groups, acute lung injury was induced by the intra-tracheal instillation of LPS(5mg/kg). Thirty minutes later, either a surfactant(ST group; 30mg/kg) or normal saline(NT group: 3ml/kg) was instilled via the trachea. Twenty-four hours after the LPS instillation, the BAL fluid was retrieved to measure the WBC count and cytokine(IL-$1{\beta}$ and IL-6) levels. The neutrophils were isolated from the BAL fluid and the nuclear protein was extracted to evaluate the NF-${\kappa}B$ activity using a eletrophoretic mobility shift assay(EMSA). Results : The WBC count of the BAL fluid of the ST group($3,221{\pm}1,914{\times}10^3/{\mu}l$) was higher than that of the control group($356{\pm}275{\times}10^3/{\mu}l$)(p<0.05) and lower than that of the NT group($5,561{\pm}1,757{\times}10^3/{\mu}l$)(p<0.05)). The BAL fluid level of IL-$1{\beta}$ from the NT group($2,064{\pm}1,082pg/ml$) was higher than those of the ST group($360{\pm}234pg/ml$)(p<0.05) and the control group(0pg/ml)p<0.05) and control group($49{\pm}62pg/ml$)(p<0.05). The NF-${\kappa}B$ activity of the neutrophilic nuclear protein in the ST group and NT group was similar. Conclusion : The surfactant, attenuates the alveolar inflammation in the acute lung injury of rats model. However, its anti-inflammatory action does no't appear to be mediated by the inhibition of NF-${\kappa}B$ activity.

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.530-541
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• 2002

Background : Pleural fluid adenosine deaminase (ADA) activity can be helpful in a differntial diagnosis of an exudative pleural effusion because it is increased in a tuberculous pleural effusion. The ADA activity is determined mainly by the lymphocyte function. Age-associated immune decline is characterized by a decrease in T-lymphocyte function. For that reason, the pleural fluid ADA level would be lower in older patients with exudative pleural effusion. This study focused on the influence of age on the pleural fluid ADA activity in patients with exudative pleural effusion. Methods : A total of 81 patients with exudative pleural effusion were enrolled in this study. In all patients, the pleural fluid ADA activity was measured using an automated kinetic method. Results : The mean age of the patients was $52.7{\pm}21.2$ years. In all patients with exudative pleural effusion, the pleural fluid ADA activity revealed a significant difference between young patients (under 65 years of age) and old patients (p<0.05), and showed a negative correlation with age (r=-0.325, p<0.05). In the 60 patients with a tuberculous pleural effusion, the pleural fluid ADA activity revealed a significant difference between the young and older patients : $103.5{\pm}36.9$ IU/L in young patients Vs. $72.2{\pm}31.6$ IU/L in old patients (p<0.05), and showed a negative correlation with age (r=-0.384, p<0.05). In the 21 patients with non-tuberculous exudative pleural effusion, the pleural fluid ADA activity of the young patients and old patients was similar : $23.7{\pm}15.3$ IU/L in young patients Vs. $16.1{\pm}10.2$ IU/L in old patients (p>0.05), and did not show any correlation with age (r=-0.263, p>0.05). The diagnostic cutoff value of pleural fluid ADA activity for tuberculous pleural effusion was lower in the older patients (25.9 IU/L) than in the younger patients (49.1 IU/L) or all patients (38.4 IU/L) with exudative pleural effusion. Conclusion : Tuberculous pleural effusion is an important possibility to consider in older patients with a clinical suspicion of a tuberculous pleural effusion, although no marked increase in the pleural fluid ADA activity is usually detected. For a diagnosis of a tuberculous pleural effusion in old patients, the cutoff for the pleural fluid ADA activity should be set lower.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.1
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• pp.9-15
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• 2007

Purpose: Repetitive transcranial magnetic stimulation (rTMS) has recently been clinically applied in the treatment of drug resistant depressed patients. There are mixed findings about the efficacy of rTMS on depression. Furthermore, the influence of rTMS on the physiology of the brain is not clear. We prospectively evaluated changes of regional cerebral blood flow (rCBF) between pre- and post-rTMS treatment in patients with drug resistant depression. Materials and Methods: Twelve patients with drug-resistant depression (7 male, 5 female; age range: $19{\sim}52$ years; mean age: $29.3{\pm}9.3$ years) were given rTMS on right prefrontal lobe with low frequency (1 Hz) and on left prefrontal lobe with high frequency (20 Hz), with 20-minute-duration each day for 3 weeks. Tc-99m ECD brain perfusion SPECT was obtained before and after rTMS treatment. The changes of cerebral perfusion were analyzed using statistical parametric mapping (SPM; t=3.14, uncorrected p<0.01, voxel=100). Results: Following areas showed significant increase in rCBF after 3 weeks rTMS treatment: the cingulate gyrus, fusiform gyrus of right temporal lobe, precuneus, and left lateral globus pallidus. Significant decrement was noted in: the precental and middle frontal gyrus of right frontal lobe, and fusiform gyrus of left occipital lobe. Conclusion: Low-frequency rTMS on the right prefrontal cortex and high-frequency rTMS on the left prefrontal cortex for 3 weeks as an add-on regimen have increased and decreased rCBF in the specific brain regions in drug-resistant depressed patients. Further analyses correlating clinical characteristics and treatment paradigm with functional imaging data may be helpful in clarifying the pathophysiology of drug-resistant depressed patients.

• Pediatric Infection and Vaccine
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• v.10 no.1
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• pp.71-80
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• 2003

Purpose : Four kinds of Haemophilus influenzae type b protein conjugate vaccines, PRPD, PRP-T, PRP-OMP and PRP-CRM197, have been developed, and PRP-T vaccines are currently produced by two manufacturer, $ActHib^{(R)}$ by Aventis and $Hiberix^{TM}$ by GlaxoSmith-Kline Biologicals. The purpose of this study is to evaluate the immunogenicity and safety of $Hiberix^{TM}$ in Korean infants. Methods : Seventy-three healthy infants(43 male infants) were recruited for this study after parental informed consent was obtained. Each infant was vaccinated at 2, 4 and 6 months of age with the study vaccine. At each visit, infants were also immunized with DTaP, trivalent oral polio vaccine and hepatitis B vaccine when indicated. The serum anti-PRP antibody was measured at prevaccination, 2 month later after the 2nd dose, and 1 month later after the 3rd dose by the ELISA method. The local and systemic adverse reactions of vaccination were monitored for 3 consecutive days after each immunization. Immunogenicity of vaccine was evaluated in infants who received all the scheduled immunization and the adverse reactions were evaluated for infants who received at least one dose of the study vaccine. Results : Among seventy three infants, enrolled in this study; sixty three(37 male infants) completed all the scheduled immunizations. The geometric mean titer(GMT) of anti-PRP antibodies at prevaccination was 0.17 ${\mu}g/mL$(95% confidence interval[CI]; 0.13~0.22). The GMT of anti-PRP antibodies increased to 4.14 ${\mu}g/mL$(95% CI; 2.65~6.48) at 2 month later after the 2nd dose of PRP-T and 14.65 ${\mu}g/mL$(95% CI; 10.83~19.81) at 1 month later after the 3rd dose. Anti-PRP antibody ${\geq}0.15$ ${\mu}g/mL$, was observed in 98.4%(95% CI; 91.8~100) after 2 doses and 100%(95% CI; 100~100) after 3 doses. Anti-PRP antibody ${\geq}1.0$ ${\mu}g/mL$, was obtained in 77.8%(95% CI; 67.5~88.0) after 2 doses, and 98.4%(95% CI; 95.3~100) after 3 doses. Most of the adverse reaction after vaccination were mild. Irritability, the most common systemic reaction, was observed in 45.5%, followed by drowsiness(30.5%), poor feeding(26.7%) and fever(5.6%). Among the local reactions tenderness was observed in 7.9%, redness(${\geq}5$ mm) in 2.8% and swelling(${\geq}5$ mm) in 1.8%. Conclusion : The PRP-T vaccine used in this study was highly immunogenic and safe in Korean young infants. The finding that high GMT and high frequency of infants with a protective titer achieved after 2 doses is consistent with the previous studies which were done with a PRP-T vaccine of other manufacturer. This study suggests that the immunization schedule of PRP-T vaccine for Korean infants may need re-evaluation.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.407-416
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• 1996

The reactive intermediates formed during the metabolism of therapeutic agents, toxicants and carcinogens by cytochromes P450 are frequently capable of covalently binding to tissue macromolecules and causing tissue damage. It has been shown that YH439, a congener of malotilate, is effective in suppressing hepatic P450 2E1 expression. The present study was designed to further establish the mechanistic basis of YH439 protection against toxicant by assessing its effects against chemical-mediated potentiated hepatotoxicity. Retinoyl palmitate (Vit-A) pretreatment of rats for 7 days substantially enhanced carbon tetrachloride hepatotoxicity, as supported by an ${\sim}5-fold$ increase in serum alanine aminotransferase (ALT) activity, as compared to $CCl_4$ treatment alone. The elevation of ALT activity due to Vit-A was completely blocked by the treatment of $GdCl_3$ a selective inhibitor of Kupffer cell activity. Concomitant pretreatment of rats with both YH439 and Vit-A resulted in a 94% decrease in Vit-A-potentiated $CCl_4$ hepatotoxicity. YH439 was also effective against propyl sulfide-potentiated $CCl_4-induced$ hepatotoxicity. Whereas propyl sulfide (50 mg/kg, 7d) enhanced $CCl_4-induced$ hepatotoxicity by >5-fold, relative to $CCl_4$ treatment alone, concomitant treatment of animals with both propyl sulfide and YH439 at the doses of 100 and 200 mg/kg prevented propyl sulfide-potentiated $CCl_4$ hepatotoxicity by 35% and 90%, respectively. Allyl sulfide, a suppressant of hepatic P450 2E1 expression, completely blocked the propyl sulfide-enhanced hepatotoxicity, indicating that propyl sulfide potentiation of $CCl_4$ hepatotoxicity was highly associated with the expression of P450 2E1 and that YH439 blocked the propyl sulfide-enhanced hepatotoxicity through modulation of P450 2E1 levels. Propyl sulfide- and $CCl_4-induced$ stimulation of lipid peroxidation was also suppressed by YH439 in a dose-related manner, as supported by decreases in malonedialdehyde production. The role of P450 2E1 induction in the potentiation of $CCl_4$ toxicity and the effects of YH439 were further evaluated using pyridine as a P450 2E1 inducer. Pyridine pretreatment substantially enhanced the $CCl_4$ hepatotoicity by 23-fold, relative to $CCl_4$ alone. YH439, however, failed to reduce the pyridine-potentiated toxicity, suggesting that the other form(s) of cytochroms P450 inducible by pyridine, but not suppressible by YH439 treatment, may play a role in potentiating $CCl_4-induced$ hepatotoxicity. YH439 was capable of blocking cadmium chloride-induced liver toxicity in mice. These results demonstrated that YH439 efficiently blocks Vit-A-enhanced hepatotoxiciy through Kupffer cell inactivation and that the suppression of P450 2E1 expression by YH439 is highly associated with blocking of propyl sulfide-mediated hepatotoxicity.

• Journal of Sasang Constitution and Immune Medicine
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• v.9 no.1
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• pp.127-153
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• 1997

Sasang-Medicine can classify all sympton with more simple classifying system than past Oriental-Medicine, because Sasang Byeon-Zeung(=classifying system of the sympton) separate by four clearly. The merit of this Sasang Byeon-Zeung can be seen more clearly on the part of the pathology of the expiratory-scattering and inspiratory-gathering of the Tae-Eum and Tae-Yang. On this view point, this thesis discussed the following subjects. 1. Investigate the theory of raising-falling and scattering-gathering developed in the Dongeui-Suse-Bowon. 2. Investigate the changes of the recognition of the Yang-Dog sympton and Jo-Yeol sympton argued as Interior-overheating-sympton of the Tae-Eum-In caused by liver's receiving heat. 3. Investigate the Yi-Je-Ma's view on the Eum-Yang in the argument of interior-overheating-sympton of the Tae-Eum-In caused by liver's receiving heat. As a result, the following conclusions were led to. 1. Dongeui-Suse-Bowon considers Spleen-Kidney has the couple motion of the raising Yang and falling Eum, and Liver-Lung has the couple motion of the expiratory-scattering and inspiratory-gathering. This theory of raising-falling and scattering-gathering is same as in the concept with the gathering. This theory of raising-falling and scattering-gathering is same as in the concept with the theory of raising-falling and floating-sinking of past Oriental-Medicine, but more consistently systematized in the pathology and prescription. 2. Dongeui-Suse-Bowon considers the Yang-Dog sympton and Jo-Yeol sympton as the interior-overheating-sympton of the Tae-Eum-In. As following the book, the fire of desire weeken the expiratory-scattering power of the lung, and deepen the shortage of the expiratory-scattering power comparison to the inspiratory-gathering power. Therfore the sympton can be treated by releasing ourselves from the desire and taking medicine strengthening the expiratory-scattering power. 3. In the early stage of the orintal medicine, they used prescriptions composed of So-Yang medicine and Tae-Eum medicine which can cool heat. Galgeun, Mawhang and Seungma were used in the age of Sanghanron, thereafter Jugoing's Jojung-Tang and Gongsin's Galgeunhaegi-Tang were developed as prescriptions of the interior-overheating-sympton of the Tae-Eum-In, and finally Tea-Uem-In Galgeunhaegi-Tang was settled by Yi-Je-Ma.

• Sleep Medicine and Psychophysiology
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• v.17 no.1
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• pp.41-49
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• 2010

Unlike the case of adult obstructive sleep apnea syndrome (OSAS), there was no consistent finding on the changes of sleep architecture in childhood OSAS. Further understanding of the sleep electroencephalogram (EEG) should be needed. Non-linear analysis of EEG is particularly useful in giving us a new perspective and in understanding the brain system. The objective of the current study is to compare the sleep architecture and the scaling exponent (${\alpha}$) from detrended fluctuation analysis (DFA) on sleep EEG between OSAS and normal children. Fifteen normal children (8 boys/7 girls, 6.0${\pm}4.3$2.2 years old) and twelve OSAS children (10 boys/2 girls, 6.4${\pm}4.3$3.4 years old) were studied with polysomnography (PSG). Sleep-related variables and OSAS severity indices were obtained. Scaling exponent of DFA were calculated from the EEG channels (C3/A2, C4/A1, O1/A2, and O2/A1), and compared between normal and OSAS children. No difference in sleep architecture was found between OSAS and normal controls except stage 1 sleep (%) and REM sleep latency (min). Stage 1 sleep (%) was significantly higher and REM latency was longer in OSAS group (9.3${\pm}4.3$4.3%, 181.5${\pm}4.3$59.9 min) than in controls (5.6${\pm}4.3$2.8%, 133.5${\pm}4.3$42.0 min). Scaling exponent (${\alpha}$) showed that sleep EEG of OSAS children also followed the 'longrange temporal correlation' characteristics. Value of ${\alpha}$ increased as sleep stages increased from stage 1 to stage 4. Value of ${\alpha}$ from C3/A2, C4/A1, O1/A2, O2/A1 were significantly lower in OSAS than in control (1.36${\pm}4.3$0.05 vs. 1.41${\pm}4.3$0.04, 1.37${\pm}4.3$0.04 vs. 1.41${\pm}4.3$0.04, 1.37${\pm}4.3$0.05 vs. 1.41${\pm}4.3$0.05, and 1.36${\pm}4.3$0.07 vs. 1.41${\pm}4.3$0.05, p<0.05). Higher stage 1 sleep (%) in OSAS children was consistent finding with OSAS adults. Lower $'{\alpha}'$ in OSAS children suggests decrease of self-organized criticality or the decreased piling-up energy of brain system during sleep in OSAS children.