노령 백서 뇌에서 Calcium binding protein 신경세포의 분포에 관한 면역조직 화학적 연구

The purpose of this study is to observe changes of distribution, number, morphology of calbindin D 28K- and parvalbumin immunoreactive neuron in brain of aging rat and comparing this finding to adult rat to approach to etiology of aging process. All of the brains（10 for control, 10 for aging）studied were perfused with 4% paraformaldehyde through the ventricle. Subjects were cutted by 4-6㎜ thickness and immersed in fixative. The post fixed blocks were cryocut into 40㎛ thick sections and immunohistochemical staining was done by free floating method. The dilution proportions of antibody were 1:10,000 for calbindin D 28K and parvalbumin. The immunoperoxidase staining was performed using the avidin-biotin-peroxidase technique. Major findings of this study were as follows: 1. Comparing to control subjects, there were reductions of number and immunolabeling of calbindin D 28K immunoreactive neurons of aging rats in hippocampus, corpus striatum, amygdala, substantia nigra, superior colliculus and cerebellum. 2. Parvalbumin immunoreactive neurous of aging rats were decreased in motor cortex, cingulate cortex, hippocampus, thalamus and amygdala. The decrease of calbindin D 28K- and parvalbumin immunoreactivity in aging rat neurous might be the result of modifications in intracellular calcium homeostasis and suggest the changes of acetylcholine and GABA which colocalized with this proteins in hippocampus. And the result supports the use of calcium channel blockers as therapeutic agent for cognition improvement in dementia. ; 本 硏究는 老化의 原因에 接近하고자 試圖된 硏究로써, 細胞內 칼슘과 結合하여 칼슘의 濃度를 낮추고 神經保護 作用을 하는 칼슘 結合 蛋白質 중 緩衝劑 蛋白質인 calbindin D 28k와 parvalbumin 含有 神經 細胞의 分布, 數 및 形態가 老化에 따라 어떠한 變化를 일으키는지 알아보기 위하여 免疫組織 化學的 硏究方法을 통하여 老齡 白鼠와 正常 對照群을 比較分析하였다. 硏究 方法은 生後 2年 以上된 老齡 白鼠에 固定液으로 4% -을 心臟을 通하여 貫流하고 腦를 摘出한 後 40㎛두께로 凍結切斷（cryocutting）하여 免疫組織化學染色（immunohistochemical staining）을 하였다. 抗體의 稀釋比率은 calbindin D 28k와 parvalbumin 모두 1:10,000 으로 하였다. Avidin-biotion complex를 使用한 ABC 方法을 이용하였다. 硏究에서 나타난 主要 結果는 다음과 같다. 1. Calbindin 含有 神經細胞의 數는 對照群에 비해 老齡白鼠에서 海馬（hippocampus）, 線條體（corpus striatum）, 扁挑（amygdala）, 黑質（substantia migra）, 위둔덕（superior colliculus）및 小腦에서 減少하였고, 大腦皮質에는 두 群間의 差異가 없었다. 2. Parvalbumin含有 神經細胞의 數와 染色性은 對照群에 比해 老齡白鼠에서 運動皮質（motor cortex）과 帶狀皮質（cingulate cortex）, 海馬, 視床（thalamus）, 扁挑에서 減少하였고, 小腦에서는 老齡群과 對照群의 差異는 없었다. 위의 사실들을 綜合하여 볼 때 老齡白鼠에서 CaBPs免疫反應性의 減少는 蛋白質이 細胞內 Ca^2+ 增加의 結果로 損傷을 받은 것으로 생각되며, 특히 海馬에서 calbindin-D 28k과 parvalbumin 反應 神經細胞의 減少는 共存하는 acetylcholine이나 GABA 神經傳達 體系의 異常을 反影하는 것으로서, 이러한 사실은 臨床的으로 認知障碍의 治療製로서 Ca^2+ 通路 遮斷劑（calcium channel blocker）의 使用 可能性을 暗示하는 것으로 判斷한다.論文槪要 Ⅰ. 序論 ------------------------------------------------------------- 1 Ⅱ. 硏究 材料 및 方法 ------------------------------------------------ 7 A. 實驗 動物 -------------------------------------------------------- 7 B. 硏究 方法 -------------------------------------------------------- 7 Ⅲ. 硏究 結果 -------------------------------------------------------- 10 A. Calbindin -------------------------------------------------------- 10 B. Parvalbumin ------------------------------------------------------ 23 Ⅳ. 考察 ------------------------------------------------------------- 36 Ⅴ. 結論 ------------------------------------------------------------- 43 參考文獻 ------------------------------------------------------------- 44 ABSTRACT ------------------------------------------------------------- 5

Neuropsychological effects of 2-week continuous positive airway pressure treatment and supplemental oxygen in patients with obstructive sleep apnea: A randomized placebo-controlled study

Study Objectives: To determine predictors of neuropsychological functioning in patients with obstructive sleep apnea (OSA) and whether treatment with 2-week continuous positive airway pressure (CPAP) or supplemental oxygen would improve cognitive functioning. Design: Randomized placebo-controlled design. Setting: University-based clinical research center. Patients: Forty-six patients with untreated OSA. Interventions: Two-week CPAP, supplemental oxygen, or placebo-CPAP. Measurements and Results: Participants underwent polysomnography and completed a neuropsychological test battery before and after treatment. Prior to treatment, patients with OSA showed diffuse impairments, particularly in terms of speed of information processing, attention and working memory, executive functioning, learning and memory, as well as alertness and sustained attention. A global deficit score at baseline was positively correlated with percentage of stage 1 sleep (p = .049) only and was not correlated with obesity, daytime sleepiness, depression, fatigue, OSA severity, and the other polysomnography variables. The 3 treatment groups (therapeutic-CPAP, supplemental oxygen, and placebo-CPAP) were compared using repeated-measures analysis of variance (ANOVA). There was no significant Time x Treatment interaction for the global deficit score. When examining individual neuropsychological test scores, two thirds of them improved with time regardless of treatment, although only Digit Vigilance - Time (p = .020) showed significant improvement specific to CPAP treatment. Conclusion: The present results suggest that Digit Vigilance - Time might be the most sensitive neuropsychological test for measuring the effects of the treatments. In general, 2 weeks of CPAP or oxygen-supplementation treatment was insufficient to show overall beneficial cognitive effects, as compared with placebo-CPAP. However, 2 weeks of CPAP treatment might be helpful in terms of speed of information processing, vigilance, or sustained attention and alertness

The association of physical activity and sleep duration with incident anxiety symptoms: A cohort study of 134,957 Korean adults

Background: Maintaining adequate levels of sleep and physical activity (PA) as self-help for the prevention of new-onset anxiety symptoms is becoming more important. Methods: A cohort study was performed with 134,957 adults, free of anxiety symptoms at baseline who underwent at least two comprehensive health screening examinations between 2012 and 2017. At baseline, the amount of PA was measured using the International Physical Activity Questionnaire-Short Form and sleep duration per day was assessed using a self-report questionnaire. The study's end point was new-onset anxiety symptoms, defined as a Beck Anxiety Inventory score of >= 19. Results: During 361,969 person-years of follow-up, 5086 participants developed case-level anxiety. Compared with a reference (0-600 METs-min/wk), a U-shaped relationship was observed between PA and case-level anxiety. The most beneficial levels of PA for reducing incident anxiety symptoms were higher in men than women (men: 1800-3000 METs-min/wk HR, 0.88 [95% CI, 0.78-0.81], 3000-6000 METs-min/wk HR, 0.81 [95% CI, 0.70-0.93]; women: 600-1,200 METs-min/wk HR, 0.86 [95% CI, 0.76-0.98]). In comparison with a reference ( < 6 h), the relationship between sleep duration and case-level anxiety also had a U-shaped pattern. The optimal sleep duration for decreasing the onset of case-level anxiety was 7-8 h, regardless of sex (men: HR, 0.75 [95% CI, 0.63-0.90]; women; HR, 0.61 [95% CI, 0.54-0.70]). Limitations: PA, sleep duration, and anxiety symptoms were measured using self-report questionnaires. Conclusions: The results of this study revealed the appropriate levels of PA and total sleep time for reducing incident anxiety symptoms

Effects of 2-week nocturnal oxygen supplementation and continuous positive airway pressure treatment on psychological symptoms in patients with obstructive sleep apnea: A randomized placebo-controlled study

Psychological symptom improvement has been observed after continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea (OSA). Because CPAP normalizes both sleep disruption and oxyhemoglobin desaturation, the mechanism of psychological symptom improvement is unclear. Using a 3-arm placebo-controlled design, we parsed out the separate effects of treatment on psychological symptoms. OSA patients (N = 38) were monitored 2 nights with polysomnography and then randomized to 2-weeks therapeutic CPAP, placebo CPAP, or O2 supplementation. Preand post-treatment, patients completed the Brief Symptom Inventory (BSI): Higher scores indicate greater severity. Repeated measures analysis of covariance reveals a Time × Treatment interaction for BSI Global Severity Index (GSI): significant pre- to post-treatment reductions in GSI with O2 supplementation and therapeutic CPAP, but not placebo CPAP. A Time × Treatment interaction was also found for depression: Depression decreased with O2 supplementation but not with therapeutic CPAP or placebo CPAP. Both therapeutic CPAP and O2 supplementation resulted in decreased psychological symptoms. Results suggest hypoxemia may play a stronger role than sleep disruption vis-à-vis OSA related psychological distress. © 2007, Lawrence Erlbaum Associates, Inc

Expression of hepatocyte growth factor/c-met by RT-PCR in meningiomas

Background: Hepatocyte growth factor (HGF) is a potent mitogenic cytokine. C-met protein, which is known to be the HGF receptor has transmembrane tyrosine kinase activity and is encoded by the c-met oncogene. The HGF/c-met signaling pathway may play various roles in the carcinogenesis of various organs. Methods: We examined HGF and c-met mRNA expression by utilizing reverse transcription polymerase chain reaction on 40 surgically resected intracranial meningiomas (25 benign, 10 atypical, and 5 anaplastic cases). Results: An HGF overexpression was detected in 28%, 50%, and 80% of the benign, atypical and anaplastic meningiomas, respectively; a high expression of HGF or the coexpression of HGF/c-met was detected in the high grade meningiomas (the atypical and anaplastic cases, p=0.046, p=0.014). An HGF expression was statistically significant in the recurrent meningiomas (p=0.003), and HGF expression was significantly lower than c-met mRNA expression in benign meningiomas (p=0.034). Conclusions: There was no correlation between histologic subtypes and HGF/c-met expression. Determination of HGF expression can be used as a molecular predictor for recurrence of meningioimas. These results suggest that HGF and c-met expression in meningiomas may be associated with anaplastic progression

The Association between Physical Activity and Anxiety Symptoms for General Adult Populations: An Analysis of the Dose-Response Relationship

Objective The aim of this study is to determine the dose-response relationship between physical activity and anxiety symptoms. Methods We included data of 124,434 participants who had comprehensive health-screening examinations from January 1st, 2012, to December 31st, 2016, in Kangbuk Samsung Hospital, Seoul and Suwon, South Korea. We measured the level of physical activity using the International Physical Activity Questionnaire-short form (IPAQ-SF) and estimated anxiety symptoms using the Beck Anxiety Inventory (BAD. BAI scores of 19 and above were defined as cases. Logistic regression was used to analyze the association between physical activity and BAI-defined anxiety. Furthermore, we assessed whether sex differences might affect the relationship between physical activity and BAI-defined anxiety by stratifying our data. Results Compared with the sedentary group (0-600 METs-min/week), individuals achieving 600-6,000 METs-min/wk had a significantly lower risk of BAI-defined anxiety with a U-shaped relationship in general adults. After stratifying our data by sex, we found that optimal ranges of physical activity were 600-9,000 METs-min/wk for men, but 1,200-3,000 METs-rnin/wk for women. Conclusion We identified a U- or J-shaped association between physical activity and anxiety symptoms, suggesting an optimal dose and upper limit of physical activity for decreasing anxiety symptoms. Optimal levels and upper limits of physical activity for reducing anxiety symptoms were higher for men than for women

The Relationship between Serum Vitamin D Levels, C-Reactive Protein, and Anxiety Symptoms

Objective The aim of study is to investigate the relationship between serum vitamin D, c-reactive protein (CRP) levels, and anxiety symptoms. Methods Serum vitamin D and CRP levels of 51,003 Korean adult participants were collected retrospectively. Anxiety symptoms were assessed using the Korean version of Beck Anxiety Inventory. Logistic regression was used to estimate the odds ratio (ORs) of anxiety symptoms by serum vitamin D and CRP levels. The regression was adjusted for covariates, and each model was adjusted mutually for vitamin D and CRP levels. Results Compared with sufficient vitamin D levels (>= 20 ng/mL), insufficient (10-19.99 ng/mL) and deficient (<10 ng/mL) vitamin D levels were significantly associated with risk of anxiety symptoms. Also, continuous vitamin D levels were negatively associated with the risk of anxiety symptoms. CRP levels did not affect the relationship between vitamin D levels and risk of anxiety symptoms. Conclusion Insufficient (10-19.99 ng/mL) and deficient (<10 ng/mL) vitamin D levels were significantly associated with risk of anxiety symptoms. After adjusting for CRP levels, the results were not changed, and no evidence of interaction between vitamin D and CRP levels was found. CRP levels did not account for the association between vitamin D levels and risk of anxiety symptoms

The association of obesity, cytokine levels, and depressive symptoms with diverse measures of fatigue in healthy subjects

Background: Fatigue is a common symptom, even among healthy individuals, but little is understood about it. We examined the associations among adiposity, depressive symptoms, cytokine levels, and multidimensional fatigue symptoms in otherwise healthy subjects. Furthermore, we examined whether obesity would account for a significant portion of fatigue and, if so, what kind of fatigue complaints appear to be related to obesity. Methods: Seventy healthy subjects (36 women and 34 men) with an average age of 36.0 years and at less than or equal to 170% of ideal body weight participated in the study. Participants had their height, weight, neck circumference, ratio of the waist to hip circumference, percentage of body fat, and plasma interleukin 6 and soluble intercellular adhesion molecule 1 concentrations measured. Their sleep was monitored with an overnight polysomnogram, and subjects completed the short form of the Multidimensional Fatigue Symptom Inventory, which measures 5 domains of fatigue, and the Center for Epidemiologic Studies-Depression Scale. Results: Obesity, as measured by body mass index (calculated as weight in kilograms divided by the square of height in meters) and percentage of body fat, was associated with general fatigue. Depression scores were significantly related to all subscales of fatigue; the highest correlation was shown with emotional fatigue. The effect of obesity on physical fatigue was significant, even after controlling for depression. In general, interleukin 6 and soluble intercellular adhesion molecule-1 levels were unrelated to measures of fatigue. Conclusions: Obesity, cytokine concentrations, and depressive symptoms explained different dimensions of fatigue as measured by the short form of the Multidimensional Fatigue Symptom Inventory. Obesity accounted for a significant portion of physical fatigue after controlling for depressive symptoms and circulating levels of interleukin 6 and soluble intercellular adhesion molecule-1