Novel transcript profiling of diffuse alveolar damage induced by hyperoxia exposure in mice: Normalization by glyceraldehyde 3-phosphate dehydrogenase

Under mechanical ventilation with high-inspired oxygen concentration, diffuse alveolar damage (DAD) was found to take place in some patients. To clarify the molecular pathophysiology of this condition we investigated the time course of gene expression changes induced by hyperoxia exposure in mouse lung using real-time quantitative polymerase chain reaction (real-time qPCR). Our results normalized by glyceraldehyde 3-phosphate dehydrogenase showed that mRNA levels of cysteine rich protein 61 (CYR61) and connective tissue growth factor (CTGF) were significantly up-regulated, while those of surfactant-associated protein C (SFTPC), cytochrome P450, 2F2 (CYP2F2), Claudin 1, (CLDN1), membrane-associated zonula occludens protein-1 (ZO-1), lysozyme (LYZS), and P lysozyme structural (LZP-S) were significantly down-regulated. Increasing level of mRNAs, each encoding CYR61 and CTGF, suggests a serious risk of fibrosing alveolitis. Decrease in levels of mRNAs for SFTPC, CYP2F2, CLDN1, ZO-1, LYZS, and LZP-S suggests alveolar dysfunction and disruption of the immune system. Moreover we confirmed apoptotic conditions, such as significant up-regulations of mRNA levels in Myc and Galectin-3. Hyperoxic condition probably yielded reactive oxygen species (ROS), which resulted in a malignant cycle of ROS production by Myc overexpression

急性期虚血性脳卒中患者から機械的血栓回収術で得られた血栓の年齢と組成は血栓回収術転帰および臨床転帰と関連していた

Introduction: Understanding the composition of stroke thrombi retrieved by mechanical thrombectomy is essential to clarify the pathogenesis of stroke. However, it is difficult to evaluate thrombus composition precisely and objectively. Immunohistochemical staining was used to evaluate thrombus composition and age. Materials and methods: Consecutive thrombi (n = 108) retrieved from patients who underwent mechanical thrombectomy for acute large-vessel ischemic stroke were retrospectively analyzed. Lytic features of granulocytes and CD163 were estimated as indicators of the age of the cardioembolic (CE) thrombus. Results: The stroke subtypes were as follows: CE, 74 cases; large artery atherosclerosis, 11; undetermined etiology, 12; and other determined etiology, 11. There were no statistical differences in thrombi composition according to stroke subtypes. The fibrin area was positively correlated with the red blood cell (RBC) and platelet areas. The following analysis was performed using CE only. Regarding age, the thrombus was judged as fresh in 30.0 % and older in 70.0 % based on the lytic features. The RBC areas of older thrombi were smaller than those of fresh thrombi. The puncture-to-reperfusion time of older thrombi was longer than that of fresh thrombi. Platelet-rich thrombi were associated with a greater number of maneuvers, a smaller prevalence of TICI 3, and unfavorable functional outcomes compared to platelet-poor thrombi. The number of CD163 positive cells in thrombi with anticoagulants was higher than in those without anticoagulants. Conclusion: Thrombus composition correlated with revascularization and clinical outcomes. The composition of an acute ischemic thrombus may reflect the pathophysiology of stroke and influence treatment efficacy.博士（医学）・甲第855号・令和4年12月22日Copyright © 2022 Elsevier Ltd. All rights reserved

Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice

社会性の発達を調節する新たな機構を発見. 京都大学プレスリリース. 2021-03-26.Neuroligin 3 (NLGN3) and neurexins (NRXNs) constitute a canonical transsynaptic cell-adhesion pair, which has been implicated in autism. In autism spectrum disorder (ASD) development of sociality can be impaired. However, the molecular mechanism underlying NLGN3-mediated social development is unclear. Here, we identify non-canonical interactions between NLGN3 and protein tyrosine phosphatase δ (PTPδ) splice variants, competing with NRXN binding. NLGN3-PTPδ complex structure revealed a splicing-dependent interaction mode and competition mechanism between PTPδ and NRXNs. Mice carrying a NLGN3 mutation that selectively impairs NLGN3-NRXN interaction show increased sociability, whereas mice where the NLGN3-PTPδ interaction is impaired exhibit impaired social behavior and enhanced motor learning, with imbalance in excitatory/inhibitory synaptic protein expressions, as reported in the Nlgn3 R451C autism model. At neuronal level, the autism-related Nlgn3 R451C mutation causes selective impairment in the non-canonical pathway. Our findings suggest that canonical and non-canonical NLGN3 pathways compete and regulate the development of sociality

トクシマシ イシカイ ノ COPD タイサク

In the national project Health Japan 21 （2nd edition） put forward in April 2013, the Ministry of Health, Labour, and Welfare specified chronic obstructive pulmonary disease （COPD） as a targeted lifestyle-related disease, in addition to cancer, heart diseases, and diabetes, and concluded that the establishment of COPD management systems is an important issue to maintain Japanese people’s healthy lives, as the number of deaths from this disease is likely to rapidly increase in the future. In Tokushima Prefecture, the mortality rate associated with COPD has been stably high over the past years ; the nation’ s highest in 2010 and third highest in 2011. In some regions of the western area, particularly mountainous regions, and southern area of the prefecture, the standardized mortality rate among males is double the national mean, highlighting the necessity of rapidly taking countermeasures. Under such circumstances, the Tokushima City Medical Association regarded COPD management as a priority item when developing annual projects this year, and organized the COPD Management and Smoking Cessation Promotion Committee in May. The medical association also presented a tentative plan to conduct association-led individualized COPD assessment at its own expense to the local government of Tokushima, with a view to materializing COPD assessment projects to clarify, evaluate, and analyze the actual situation, including surveys on citizens’ recognition of COPD and those conducted by family doctors to examine the statuses of their patients, involving the local government in the future. During deliberations to examine the feasibility of this plan, the local government proposed a new COPD assessment plan based on the conventional mass pulmonary cancer examination system, in order to deal with those at a high risk of COPD ; following some revisions, the new plan was adopted. The plan consisted of the following steps : > Targeting those meeting the 3 diagnostic criteria specified in the pulmonary cancer interview sheet for COPD assessment : 1） age of 60 or over ; 2） previous smoking habit ; 3） presence of at least one of the subjective COPD symptoms （chronic coughing, sputum, and shortness of breath during activity）. > Providing these patients with a free-consultation coupon to undergo assessment in a registered primary medical examination institution. > Conducting airway obstruction evaluation in primary medical examination institutions using the mass COPD screening interview sheet （COPD-PSTM） and spirometry. > Conducting insurance-covered medical examinations, such as the respiratory function test, chest XP, and CT scans, in secondary medical examination institutions （chest physicians） to establish a definite diagnosis. > Reporting the results of these examinations to family doctors. > If treatment is necessary, developing initial pharmacotherapy plans as part of the standardized treatment of COPD for approximately 3 months, which are implemented by family doctors. In consideration of the rapidly aging Japanese population, the number of potential COPD patients aged 40 and over is expected to reach nearly 7 million soon. In order to deal with such a large number of COPD patients, it is primary care physicians’ duty to provide early diagnosis and treatment, and local medical associations are charged with promoting spirometry through their activities as part of COPD assessment projects, aiming to establish cooperative systems to manage the disease between primary care physicians providing treatment during the stable period and chest physicians providing it during the exacerbation period. As future perspectives, spirometry-promoting seminars to be held in clinical environments are being considered ; participation in these seminars will be a requirement for registered primary COPD examination institutions, and those who have completed such programs will be Tokushima City Medical Association-certified COPD specialists （tentative name）. It is expected that these approaches to carry out the nation’s first COPD assessment projects will improve clinical environments in communities, such as support for smoking cessation, medical professionals’ knowledge of COPD, and the standardization of diagnosis and treatment