Takano T.,Shiga University of Medical Science
Developmental Neuroscience | Year: 2015
The neurobiological basis for autism remains poorly understood. However, the neuroinflammation processes play an important role in the induction of autistic behavioral changes. Microglial cells can exhibit widely differing functions during brain development, including synaptogenesis and stem cell proliferation, in addition to playing a role in the innate immunity. Mounting evidence indicates that microglial activation or dysfunction can profoundly affect neural development, resulting in neurodevelopmental disorders, including autism. These mechanisms in autism have been investigated using neuropathological studies of human autopsy brains, a large number of murine experimental models and in vivo neuroimaging studies of the human brain. The purpose of this review is to discuss microglial activation or dysfunction and to highlight the detrimental role that microglia play in the development of autism. The recent advances presented in this review support that further elucidation of the mechanisms and kinetics of microglial responses will help to establish a window for therapeutic intervention in individuals with autism. © 2015 S. Karger AG, Basel.
Takashima N.,Shiga University of Medical Science
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco | Year: 2010
Few studies have reported the relationship between smoking in middle age and long-term risk of impaired activities of daily living (ADL). We analyzed 2,276 men and women aged 47-59 years at the baseline survey of NIPPON DATA80 in 1980. At the follow-up survey in 1999, ADL was surveyed among 1890 survivors. Multivariate-adjusted odds ratio (AOR) and 95% CI of impaired ADL or of composite outcome of either death or impaired ADL according to baseline smoking status were calculated by multiple logistic regression analyses. In 1999, 386 participants were dead, and 75 participants had impaired ADL. Compared with nonsmokers, AOR (95% CI) of impaired ADL was significantly higher in current smokers at baseline (odds ratio [OR] 2.11 [1.09-4.06]). Compared with nonsmokers, AOR of impaired ADL was higher as the number of cigarettes increased (OR 2.04 [1.02-4.06] for <20 cigarettes/day and OR 2.35 [0.94-5.88] for >20 cigarettes/day; p for trend = .04). AOR of composite outcome for current smoking was 1.83 (1.37-2.41). Smoking in middle age would increase future risks of impaired ADL. Smoking cessation may be important to prevent future impairment of ADL as well as death.
Murakami Y.,Shiga University of Medical Science
Journal of Epidemiology | Year: 2014
Meta-analysis of individual participant data (IPD meta-analysis) has several advantages over meta-analysis using aggregated published data, including the possibility of using statistical methods such as a fine stratification analysis, interaction analysis between 2 risk factors, and absolute risk estimation. The Evidence for Cardiovascular Prevention from Observational Cohorts in Japan Study (EPOCH-JAPAN), which was initiated in 2005, is a collaborative research project for IPD meta-analysis and includes 13 participating cohort studies in Japan. We generated 2 pooled databases with data on all-cause mortality (n = 199 047) and cardiovascular outcomes (n = 90 528) and applied a stratified Cox model to account for the different baseline hazards between cohorts. The results of our analyses show the age- and sex-specific associations between all-cause and cardiovascular disease mortality and established cardiovascular risk factors (blood pressure, smoking, total cholesterol, proteinuria, and kidney function). During the 9 years of its existence, the results generated by EPOCH-JAPAN have had important implications for clinical medicine and public health policy in Japan. The project is expected to draw upon new analytical methods such as interaction analysis and absolute risk evaluation in the near future. We believe that, over the next decade, this project will continue to provide new insights that can be applied to research on other Asian populations. © 2014 Yoshitaka Murakami.
Shimizu W.,Japan National Cardiovascular Center Research Institute |
Horie M.,Shiga University of Medical Science
Circulation Research | Year: 2011
Since 1995, when a potassium channel gene, hERG (human ether-à-go- go-related gene), now referred to as KCNH2, encoding the rapid component of cardiac delayed rectifier potassium channels was identified as being responsible for type 2 congenital long-QT syndrome, a number of potassium channel genes have been shown to cause different types of inherited cardiac arrhythmia syndromes. These include congenital long-QT syndrome, short-QT syndrome, Brugada syndrome, early repolarization syndrome, and familial atrial fibrillation. Genotype-phenotype correlations have been investigated in some inherited arrhythmia syndromes, and as a result, gene-specific risk stratification and gene-specific therapy and management have become available, particularly for patients with congenital long-QT syndrome. In this review article, the molecular structure and function of potassium channels, the clinical phenotype due to potassium channel gene mutations, including genotype-phenotype correlations, and the diverse mechanisms underlying the potassium channel gene-related diseases will be discussed. © 2011 American Heart Association, Inc.
Tsuchiya K.,Shiga University of Medical Science
International journal of nanomedicine | Year: 2011
The biodynamics of ultrasmall and small superparamagnetic iron oxide (USPIO and SPIO, respectively) particles that were injected intraperitoneally into 36 C57BL/6 mice were investigated chronologically. Their distribution was studied histologically at six time points by measuring iron-positive areas (μm 2) in organ sections stained with Prussian blue. The uptake of the differently sized particles was also compared by cultured murine macrophages (J774.1). Iron-positive areas in the liver were significantly larger in the mice injected with USPIO than those injected with SPIO at the first three time points (P < 0.05). The amount of USPIO in the lung parenchyma around the airway was larger than that of SPIO at four time points (P < 0.05); distribution to the lymph nodes was not significantly different. The amount of iron was significantly larger in SPIO- than USPIO-treated cultured cells (P < 0.05). In conclusion, it is suggested that intra peritoneally injected USPIO particles could be used more quickly than SPIO to make Kupffer images of the liver and that both agents could help get lymph node images of similar quality.