Configuration of the active Mg-ATP complex in protein kinase C reaction

AbstractTo probe the active site structure of protein kinase C stereochemical studies were carried out by using ATPβs. The enzyme utilizes either one of the diastereomers (Sp and Rp) of ATPβs almost equally well as a substrate. This result contrasts with that for cyclic AMP-dependent protein kinase, suggesting that the topography of the nucleotide-binding site is significantly different between the two kinases

Association of cognitive performance with interleukin-6 receptor Asp358Ala polymorphism in healthy adults

Wechsler adult intelligence scale-revised was performed in 576 healthy adults to examine whether a functional polymorphism (Asp358Ala) of the IL-6 receptor (IL-6R) gene is associated with cognitive performance. Verbal intelligence quotient in Asp homozygotes was significantly higher compared to Ala carriers (P = 0.005). Compared to Ala carriers, Asp homozygotes performed better in the verbal subtests requiring long-term memory stores. Elevated IL-6 and soluble IL-6R levels in Ala carriers may have negative impact on acquiring verbal cognitive ability requiring long-term memory.ArticleJOURNAL OF NEURAL TRANSMISSION. 119(3):313-318 (2012)journal articl

The State of Studies of Japanese Constitution in the U. S. and Europe <Research Note>

本文に記したように本稿は，2013年度～2015年度にかけて取得した，科研費・基盤研究（C）「欧米諸国における日本憲法研究の状況をめぐる憲法学的検証」（研究課題番号：25380038）に基づく研究成果である（なお，本研究の一部において，平成27年度慶磨義塾学事振興資金に基づく調査研究も反映されている）

Association of interleukin-1 beta genetic polymorphisms with cognitive performance in elderly females without dementia

Interleukin-1 beta (IL-1 beta) is considered to have a role in age-related cognitive decline. A recent study has shown that a promoter polymorphism of the IL-1 beta gene (rs16944) is associated with cognitive performance in elderly males without dementia. In this study, we examined whether polymorphisms of the IL-1 beta gene also influence cognitive functions in elderly females. Cognitive functions were assessed by the Wechsler adult intelligence scale-revised (WAIS-R) in 99 elderly (>= 60 years) females without dementia. We selected five tagging polymorphisms from the IL-1 beta gene and examined the associations with the WAIS-R scores. Significant associations were found between verbal intelligence quotient (IQ) and the genotypes of rs1143634 and rs1143633 (P = 0.0037 and P = 0.010, respectively). No significant associations of rs16944 genotype were found with verbal or performance IQ. However, individuals homozygous for the G allele of rs16944 achieved higher scores in digit span compared with their counterpart, which is consistent with the previous findings in males. These results suggest that IL-1 beta gene variation may have a role in cognitive functions in aging females as well as males. Journal of Human Genetics (2011) 56, 613-616; doi:10.1038/jhg.2011.56; published online 26 May 2011ArticleJOURNAL OF HUMAN GENETICS. 56(8):613-616 (2011)journal articl

More severe impairment of manual dexterity in bipolar disorder compared to unipolar major depression

Background: Mood disorders are associated with various neurocognitive deficits. However, few studies have reported the impairment of motor dexterity in unipolar depression and bipolar disorder. In the present study, manual dexterity was compared between unipolar major depression, bipolar disorder, and healthy controls. Methods: Manual dexterity was assessed by the Purdue pegboard test in 98 patients with unipolar major depression, 48 euthymic or depressed patients with bipolar disorder, and 158 healthy controls, matched for age and gender. Results: Compared to healthy controls, sum of the scores of right, left, and both hands subtests (R + L+ B) was significantly lower in both patients with unipolar depression and bipolar disorder (P= 0.0034 and P<0.0001, respectively). Furthermore, R + L + B was significantly lower in bipolar disorder compared to unipolar depression (P=0.0016). Lithium dose and chlorpromazine equivalent dose of antipsychotics were significantly negatively correlated with some of the subtest scores. On the other hand, depression severity did not significantly correlate with any of the subtest scores. Difference in R + L+ B between unipolar depression and bipolar disorder remained statistically significant even after controlling for gender, age, lithium dose, and chlorpromazine equivalent dose (P = 0.0028). Limitations Bipolar patients during manic episode were not included in the study. Conclusions: Gross movement dexterity was impaired in both patients with unipolar depression and bipolar disorder. The severity of impairment was significantly greater in patients with bipolar disorder. The functional difference between unipolar and bipolar patients may suggest different pathological conditions between the two depressive disorders.ArticleJOURNAL OF AFFECTIVE DISORDERS. 136(3):1047-1052 (2012)journal articl

Difference in Temperament and Character Inventory scores between depressed patients with bipolar II and unipolar major depressive disorders

Background: Although some core personality variables are known to be characteristic of unipolar or bipolar depression, few studies have compared the personality profile between these two disorders. Methods: Temperament and Character Inventory (TCI) was employed to assess the personality of 36 depressed patients with bipolar II disorder (BPII), 90 patients with unipolar major depressive disorder (UP), and 306 healthy controls. The TCI was administered during the depressive episode in BPII and UP patients so that the results can be applied in a clinical setting. Results: Significantly higher scores in harm avoidance (p<0.0001) and lower scores in self-directedness (p<0.0001) and cooperativeness (p<0.05) were observed in both BPII and UP patients compared to controls. Lower novelty seeking in UP patients compared to BPII patients and controls was observed in females (p<0.0001, p<0.01. respectively). A significant difference in self-transcendence score was observed between BPII and UP patients in females (p<0.0005), with higher scores in BPII (p = 0.009) and lower scores in UP (p = 0.046) patients compared to controls. A logistic regression model predicted BPII in depressed females based on novelty seeking and self-transcendence scores with a sensitivity of 89% and a specificity of 73%, but did not accurately predict BPII in males. Limitations: Patients in our study were limited to those receiving outpatient treatments, and bipolar patients were limited to those with BPII. Conclusions: Novelty seeking and self-transcendence scores of TCI might be useful in the differentiation of UP and BPII in female patients.ArticleJOURNAL OF AFFECTIVE DISORDERS. 132(3):319-324 (2011)journal articl

The renin–angiotensin system promotes arrhythmogenic substrates and lethal arrhythmias in mice with non-ischaemic cardiomyopathy

[Aims]The progression of pathological left ventricular remodelling leads to cardiac dysfunction and contributes to the occurrence of malignant arrhythmias and sudden cardiac death. The underlying molecular mechanisms remain unclear, however. Our aim was to examine the role of the renin–angiotensin system (RAS) in the mechanism underlying arrhythmogenic cardiac remodelling using a transgenic mouse expressing a cardiac-specific dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). This mouse model exhibits progressive cardiac dysfunction leading to lethal arrhythmias. [Methods and results]Subcutaneous administration of aliskiren, a direct renin inhibitor, significantly suppressed the progression of pathological cardiac remodelling and improved survival among dnNRSF-Tg mice while reducing arrhythmogenicity. Genetic deletion of the angiotensin type 1a receptor (AT1aR) similarly suppressed cardiac remodelling and sudden death. In optical mapping analyses, spontaneous ventricular tachycardia (VT) and fibrillation (VF) initiated by breakthrough-type excitations originating from focal activation sites and maintained by functional re-entry were observed in dnNRSF-Tg hearts. Under constant pacing, dnNRSF-Tg hearts exhibited markedly slowed conduction velocity, which likely contributes to the arrhythmogenic substrate. Aliskiren treatment increased conduction velocity and reduced the incidence of sustained VT. These effects were associated with suppression of cardiac fibrosis and restoration of connexin 43 expression in dnNRSF-Tg ventricles. [Conclusion]Renin inhibition or genetic deletion of AT1aR suppresses pathological cardiac remodelling that leads to the generation of substrates maintaining VT/VF and reduces the occurrence of sudden death in dnNRSF-Tg mice. These findings demonstrate the significant contribution of RAS activation to the progression of arrhythmogenic substrates

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