青年期双極II型障害におけるBDNFとセロトニン誘発による血小板カルシウムの測定

金沢大学附属病院研究目的:児童青年期に抑うつ症状で発症した場合、単極性のうつ病か、双極性II型障害であるのか鑑別が容易でない。そのため鑑別において生物学的マーカーの有用性を検討した。研究方法:当初はBDNF(Brain derived neurotrophic factor)と血小板におけるセロトニン誘発によるカルシウムの濃度の変化を観察する予定であったが、後者は実験結果にばらつきが多く有意な結果が得られなかったので、計画を変更し、前頭葉機能検査、近赤外線スペクトロスコピー(NIRS)による前頭葉の血流変化、そして従来計画していたBDNFのほか、ノルアドレナリン代謝産物の測定を行った。また検査のタイミングについても当初は大うつ病エピソード、軽躁病エピソード、混合性エピソードについて行う予定であったが、後の2つの時期については、短い期間で妥当する時期を認めず、来院時の抑うつ状態での検討のみとした。研究成果:前頭葉機能検査については言語記憶、視覚記憶の領域で正常群に対して低下しているものと、ほぼ変わりないものに分けられ、特に前者では近赤外線スペクトロスコピーでも血流の上昇が正常群に比べ低かった。またBDNFについても前者のほうが、より低下していた。しかしノルアドレナリン代謝産物については差を認めなかった。従って前頭葉機能検査、NIRS,BDNFは生物学的マーカーとして有用であると考えられた。すなわち成人で得られた結果とほぼ同様の結論が10台の患者でも認められた。なお臨床的にはMDQ(Mood disorder questionnaire)を用いて両者の鑑別に用いているが、MDQによる項目数と比較した場合、MDQで7以上を指標にすると、ほぼ同様に2群に分けることができた。研究課題/領域番号:19925030, 研究期間(年度):2007出典：「青年期双極II型障害におけるBDNFとセロトニン誘発による血小板カルシウムの測定」研究成果報告書　課題番号19925030（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-19925030/)を加工して作

Oxytocin signal and social behaviour: comparison among adult and infant oxytocin, oxytocin receptor and CD38 gene knockout mice.

金沢大学医薬保健研究域医学系Oxytocin in the hypothalamus is the biological basis of social recognition, trust, love and bonding. Previously, we showed that CD38, a proliferation marker in leukaemia cells, plays an important role in the hypothalamus in the process of oxytocin release in adult mice. Disruption of Cd38 (Cd38 (-/-)) elicited impairment of maternal behaviour and male social recognition in adult mice, similar to the behaviour observed in Oxt and oxytocin receptor (Oxtr) gene knockout (Oxt (-/-) and Oxtr (-/-), respectively) mice. Locomotor activity induced by separation from the dam was higher and the number of ultrasonic vocalisation calls was lower in Cd38 (-/-) than Cd38( +/+) pups. However, these behavioural changes were much milder than those observed in Oxt (-/-) and Oxtr (-/-) mice, indicating less impairment of social behaviour in Cd38 (-/-) pups. These phenotypes appeared to be caused by the high plasma oxytocin levels during development from the neonatal period to 3-week-old juvenile mice. ADP-ribosyl cyclase activity was markedly lower in the knockout mice from birth, suggesting that weaning for mice is a critical time window of plasma oxytocin differentiation. Breastfeeding was an important exogenous source of plasma oxytocin regulation before weaning as a result of the presence of oxytocin in milk and the dam\u27s mammary glands. The dissimilarity between Cd38 (-/-) infant behaviour and those of Oxt (-/-) or Oxtr (-/-) mice can be explained partly by this exogenous source of oxytocin. These results suggest that secretion of oxytocin into the brain in a CD38-dependent manner may play an important role in the development of social behaviour

A custom magnetoencephalography device reveals brain connectivity and high reading/decoding ability in children with autism

A subset of individuals with autism spectrum disorder (ASD) performs more proficiently on certain visual tasks than may be predicted by their general cognitive performances. However, in younger children with ASD (aged 5 to 7), preserved ability in these tasks and the neurophysiological correlates of their ability are not well documented. In the present study, we used a custom child-sized magnetoencephalography system and demonstrated that preserved ability in the visual reasoning task was associated with rightward lateralisation of the neurophysiological connectivity between the parietal and temporal regions in children with ASD. In addition, we demonstrated that higher reading/decoding ability was also associated with the same lateralisation in children with ASD. These neurophysiological correlates of visual tasks are considerably different from those that are observed in typically developing children. These findings indicate that children with ASD have inherently different neural pathways that contribute to their relatively preserved ability in visual tasks

Quantitative assessment of harmonic power doppler myocardial perfusion imaging with intravenous levovist™ in patients with myocardial infarction: comparison with myocardial viability evaluated by coronary flow reserve and coronary flow pattern of infarct-related artery

BACKGROUND: Myocardial contrast echocardiography and coronary flow velocity pattern with a rapid diastolic deceleration time after percutaneous coronary intervention has been reported to be useful in assessing microvascular damage in patients with acute myocardial infarction. AIM: To evaluate myocardial contrast echocardiography with harmonic power Doppler imaging, coronary flow velocity reserve and coronary artery flow pattern in predicting functional recovery by using transthoracic echocardiography. METHODS: Thirty patients with anterior acute myocardial infarction underwent myocardial contrast echocardiography at rest and during hyperemia and were quantitatively analyzed by the peak color pixel intensity ratio of the risk area to the control area (PIR). Coronary flow pattern was measured using transthoracic echocardiography in the distal portion of left anterior descending artery within 24 hours after recanalization and we assessed deceleration time of diastolic flow velocity. Coronary flow velocity reserve was calculated two weeks after acute myocardial infarction. Left ventricular end-diastolic volumes and ejection fraction by angiography were computed. RESULTS: Pts were divided into 2 groups according to the deceleration time of coronary artery flow pattern (Group A; 20 pts with deceleration time ≧ 600 msec, Group B; 10 pts with deceleration time < 600 msec). In acute phase, there were no significant differences in left ventricular end-diastolic volume and ejection fraction (Left ventricular end-diastolic volume 112 ± 33 vs. 146 ± 38 ml, ejection fraction 50 ± 7 vs. 45 ± 9 %; group A vs. B). However, left ventricular end-diastolic volume in Group B was significantly larger than that in Group A (192 ± 39 vs. 114 ± 30 ml, p < 0.01), and ejection fraction in Group B was significantly lower than that in Group A (39 ± 9 vs. 52 ± 7%, p < 0.01) at 6 months. PIR and coronary flow velocity reserve of Group A were higher than Group B (PIR, at rest: 0.668 ± 0.178 vs. 0.248 ± 0.015, p < 0.0001: during hyperemia 0.725 ± 0.194 vs. 0.295 ± 0.107, p < 0.0001; coronary flow velocity reserve, 2.60 ± 0.80 vs. 1.31 ± 0.29, p = 0.0002, respectively). CONCLUSION: The preserved microvasculature detecting by myocardial contrast echocardiography and coronary flow velocity reserve is related to functional recovery after acute myocardial infarction

Consciousness Level and Off‐Hour Admission Affect Discharge Outcome of Acute Stroke Patients: A J‐ASPECT Study

Background-Poor outcomes have been reported for stroke patients admitted outside of regular working hours. However, few studies have adjusted for case severity. In this nationwide assessment, we examined relationships between hospital admission time and disabilities at discharge while considering case severity. Methods and Results-We analyzed 35 685 acute stroke patients admitted to 262 hospitals between April 2010 and May 2011 for ischemic stroke (IS), intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). The proportion of disabilities/death at discharge as measured by the modified Rankin Scale (mRS) was quantified. We constructed 2 hierarchical logistic regression models to estimate the effect of admission time, one adjusted for age, sex, comorbidities, and number of beds; and the second adjusted for the effect of consciousness levels and the above variables at admission. The percentage of severe disabilities/death at discharge increased for patients admitted outside of regular hours (22.8%, 27.2%, and 28.2% for working-hour, off-hour, and nighttime; P<0.001). These tendencies were significant in the bivariate and multivariable models without adjusting for consciousness level. However, the effects of off-hour or nighttime admissions were negated when adjusted for consciousness levels at admission (adjusted OR, 1.00 and 0.99; 95% CI, 1.00 to 1.13 and 0.89 to 1.10; P=0.067 and 0.851 for off-hour and nighttime, respectively, versus working-hour). The same trend was observed when each stroke subtype was stratified. Conclusions-The well-known off-hour effect might be attributed to the severely ill patient population. Thus, sustained stroke care that is sufficient to treat severely ill patients during off-hours is important

Two genetic variants of CD38 in subjects with autism spectrum disorder and controls

金沢大学医薬保健研究域医学系The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p 70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD. © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society

ウエアラブルセンサーを用いた思春期うつ状態の早期発見

弘前大学 / 金沢大学附属病院神経科精神科中学生29名について、ウエアラブルセンサーを用いて、心電図から心拍変動の変化、加速度計から運動量と睡眠指標を計測した。平均年齢13.7歳、うつ状態DSRS 8.9　ヤングのネット依存度は40.5、自閉症指数14.9、ADHD-RS 不注意5.6　多動衝動性2.2、不安を評価したSTAI 特性不安41.8、状態不安37.7、スマートフォン依存度22となった。男子が女子に比べADHD傾向が高いほかは、他の指標で性差を認めなかった。ネット依存度と夜間のHFの回復度には相関を認め、ネット依存度が高いほど、夜間の自律神経の変化が大きかった。起立試験の心拍数の変化は夜間のHFの回復度と相関を認めた。For 29 junior high school students, wearable sensors were used to measure changes in heart rate variability from electrocardiograms, and physical activity and sleep indices from accelerometers.Mean age 13.7 years, Depression DSRS 8.9 Young\u27s internet dependence was 40.5,.Autism Index 14.9, ADHD-RS Inattention 5.6 Hyperactivity Impulsivity 2.2, STAI assessed anxiety 41.8 for trait anxiety, 37.7 for state anxiety, and 22 for smartphone dependence. Other than boys being more prone to ADHD than girls, no gender differences were found in other indicators. There was a correlation between the degree of internet dependence and the degree of HF recovery at night, and the higher the degree of internet dependence, the greater the change in autonomic nervous system at night. The higher the level of internet dependence, the greater the nocturnal autonomic changes. The change in heart rate in the orthostatic test was correlated with the nocturnal HF recovery.研究課題/領域番号:18K07591, 研究期間(年度):2018-04-01 - 2021-03-31出典：「ウエアラブルセンサーを用いた思春期うつ状態の早期発見」研究成果報告書　課題番号18K07591（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-18K07591/18K07591seika/）を加工して作

An Inquiry on the Theory of Organization about School-Business Partnerships : Focusing on \u22Collaborative Culture\u22 between Organizations

はじめに I.パートナーシップ組織化論における組織文化的アプローチの生成 II.パートナーシップにおける組織文化的アプローチの特質 1.組織文化の概念構造 2.組織文化レベルにおける学校・企業の相違 3.組織構造レベルにおける学校・企業の相違 4.学校文化と企業文化による「協働文化」形成の枠組みに関する試論 III.パートナーシップ活動事例を通じた組織文化的アプローチの若干の検

Abstract of Doctoral dissertation

アメリカにおける学校と企業の連携に関する組織論的研究[大野]学校における組織文化と教育相談機能との連関性に関する研究[増田