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Objectives: Anti‐acetylcholine receptor antibodies (AChR Ab) are one of the pathogenic autoantibodies in myasthenia gravis (MG), and they are specifically mentioned in the Japanese clinical guidelines for MG. In the serological diagnosis and measurement of autoantibodies as an adjunct marker for MG, the radioimmunoassay (RIA) method has been conventionally used as the gold standard. However, there have been several worldwide concerns regarding the use of radioisotopes. In this study, we evaluated the performance of the EUROIMMUN AChR Ab enzyme‐linked immunosorbent assay (ELISA) in comparison with RIA. Methods: ELISA reproducibility and dilution linearity were analyzed using AChR Ab‐positive samples. Sera from 50 patients with suspected MG and 50 healthy donors were used to assess the correlation and qualitative agreement between the two methods. Results: The ELISA showed good interassay precision and dilution linearity. The correlation coefficient, sensitivity, specificity and overall agreement of the ELISA in comparison with the conventional RIA amounted to 0.87, 98%, 92% and 95% (kappa = 0.895), respectively. Analysis of the discordant results suggested that the ELISA might be more capable of detecting low AChR Ab reactivity in patients with suspected MG. Conclusions: The AchR Ab ELISA provides a reliable tool for the quantification of AchR Ab, supporting the diagnosis of MG. As a non‐isotopic assay with good precision, shorter handling time and high correlation with the conventional RIA, the AChR ELISA could be a useful alternative in the laboratory routine. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the impacts of earlier traumatic events on the mental health of older adults, in terms of mental disorders and mental well-being, according to sociodemographic variables, trauma-related characteristics, and personality traits in a nationally representative sample of older Koreans.Methods: A total of 1,621 subjects aged 60 to 74 years from a Korean national epidemiological survey of mental disorders responded face-to-face interviews. The Korean Composite International Diagnostic Interview was used to investigate lifetime trauma exposure (LTE) and psychiatric diagnoses. The EuroQol health classification system and life satisfaction scale were used to assess quality of life (QoL), and the Big Five Inventory-10 (BFI-10) to measure personality traits.Results: Five-hundred and seventy-seven subjects (35.6%) reported a history of LTE (mean age at trauma, 30.8 years old). Current mental disorders were more prevalent in elderly people with LTE, while better current QoL was more frequent in those without LTE. Among older people with LTE, lower extraversion and higher neuroticism increased the risk of current mood or anxiety disorders, whereas higher extraversion increased the probability of experiencing mental well-being after adjusting for sociodemographic and trauma-related variables.Conclusion: Personality traits, especially extraversion, and neuroticism, may be useful for predicting the mental health outcomes of LTE in older adults. Further longitudinal studies investigating the relationship between traumatic events and mental health outcomes are needed. [ABSTRACT FROM AUTHOR]

The (Ba[sub 0.5]Sr[sub 0.5])TiO[sub 3] (BST) thin films were deposited on the LaNiO[sub 3]/Pt(111)/Ti/SiO[sub 2]/Si [LNO/ Pt(lll)] and LaNiO[sub 3]/Pt(200)/SiO[sub 2]/Si [LNO/Pt(200)] substrates by metalorganic deposition process. The BST films directly grown on the Pt(200) and Pt(lll) substrates exhibited random orientation. In case of the LNO/Pt(111) substrates, the BST film was also randomly oriented, but the insertion of LNO interlayer on the Pt(200) substrates caused the growth of (100) textured BST films. The dielectric constant of the 350-nm-thick BST films on LNO/Pt(200) was around 400, which was higher than that of the films on LNO/Pt(111) (around 340). This result was attributed to the fact that the polar axis of the (100) oriented film was more tilted away from the normal to the film surface than that of randomly oriented film. Also, the tunabilities of BST films deposited on the LNO/ Pt(200) and LNO/Pt(111) substrates were nearly 60% and 51% at the applied electric field of 400 kV/cm, respectively. Improved tunability has been attributed to the (100) texture of the film leading to an enhancement of the in-plane oriented polar axis. [ABSTRACT FROM AUTHOR]

Beta amyloid peptide is generated from amyloid precursor protein (APP) by proteolytic cleavage of beta- and gamma-secretases, and plays a critical role in the pathogenesis of Alzheimer's disease. Since gamma-secretase cleaves several proteins including APP and Notch in a number of cell types, it is important to understand the conditions determining gamma-secretase substrate specificity. In the present study, inhibition of Rac1 attenuated gamma-secretase activity for APP, resulting in decreased production of the APP intracellular domain but accumulated C-terminal fragments (APP-CTF). In contrast, Rac1 inhibitor, NSC23766 increased production of the Notch1 intracellular domain but slightly decreased the ectodomain-shed form of Notch1 (NotchDeltaE). To elucidate the mechanism underlying these observations, we performed co-immunoprecipitation experiments to analyze the interaction between Rac1 and presenilin1 (PS1), a component of the gamma-secretase complex. Inhibition of Rac1 enhanced its interaction with PS1. Under the same condition, PS1 interacted more strongly with NotchDeltaE than with APP-CTF. Our results suggested that PS1 determines the preferred substrate for gamma-secretase between APP and Notch1, depending on the activation status of Rac1.

Both active and passive immunization to eliminate amyloid plaques from the brain of patients with Alzheimer's disease (AD) have confirmed that amyloid beta (Abeta) vaccination does not only result in clearance of Abeta plaques but improves behavioral-cognitive deficits in animal models of AD. In the present study, the levels of naturally occurring serum antibodies against Abeta were measured in Tg2576 mice at various ages using ELISA to determine the relationship between aging and the level of anti-Abeta autoantibody. The level of anti-Abeta antibody fell significantly at the age of 9 months, at the age when amyloid plaques started to appear in the brain of Tg2576 mice, and was persistently low thereafter. However, serum immunoglobulin (Ig) level was elevated in older transgenic mice compared with younger transgenic mice suggesting that the reduced level of anti-Abeta autoantibody was not merely due to deterioration of the immune response in aged Tg2576 mice.

Constitutive and PKC-regulated alpha-secretase pathways have been reported to produce the secreted form of alpha-secretase-derived APP (sAPPalpha). Here, we examined putative role of furin in the regulation of alpha-secretase activity in vitro and in vivo. Overexpression of the prodomain of furin and infection with a furin-specific inhibitor significantly reduced the levels of sAPPalpha regardless of PKC activity, whereas total APP levels remained unchanged. Furin mRNA levels in the brains of AD patients and Tg2576 mice were significantly lower than those in controls, whereas ADAM10 and TACE mRNA levels were much alike between Tg2576 and littermate mice. Moreover, the injection of furin-adenovirus into Tg2576 mouse brains markedly increased alpha-secretase activity and reduced beta-amyloid protein (Abeta) production in infected brain regions. Our results suggest that furin enhances alpha-secretase activity via the cleavage of ADAM10 and TACE, and that attenuated furin activity is connected to the production of Abeta.