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α-Synuclein (α-Syn) is a protein related to synucleinopathies with high expression in the central nervous system and erythrocytes which are a major source of peripheral α-Syn. Recent reports have suggested the presence of α-Syn within extracellular vesicles (EVs) derived from erythrocytes, potentially contributing to the pathogenesis of synucleinopathies. While Lewy bodies, intracellular inclusions containing aggregated α-Syn, are prominently observed within the brain, their occurrence in peripheral neurons implies the dissemination of synucleinopathy pathology throughout the body via the propagation of α-Syn. In this study, we found erythrocytes and circulating EVs obtained from plasma contained α-Syn, which was separated into four major forms using high-resolution clear native-PAGE and isoelectric focusing. Notably, erythrocyte α-Syn was classified into full-length and C-terminal truncated forms, with truncation observed between Y133 and Q134 as determined by LC–MS/MS analysis. Our finding revealed that C-terminally truncated α-Syn, which was previously reported to exist solely within the brain, was also present in erythrocytes and circulating EVs obtained from plasma. [ABSTRACT FROM AUTHOR]

α-Synuclein is a protein linked to various synuclein-associated diseases ('synucleinopathies'), including Parkinson's disease, dementia with Lewy Bodies and multiple system atrophy, and is highly expressed in the central nervous system and in erythrocytes. Moreover, α-synuclein-containing erythrocyte-derived extracellular vesicles may be involved in the pathogenesis of synucleinopathies and their progression across the blood–brain barrier. Several post-translational modifications of α-synuclein have been reported in brain inclusions, including S129 phosphorylation, but fewer have been found in erythrocytes. In this study, we analysed the post-translational modifications of erythrocyte α-synuclein using liquid chromatography–mass spectrometry. We found that all lysine residues in the α-synuclein protein could be modified by acetylation, glycation, ubiquitination or SUMOylation but that phosphorylation, nitration and acylation were uncommon minor post-translational modifications in erythrocytes. Since the post-translational modification of lysine residues has been implicated in both membrane association and protein clearance, our findings provide new insight into how synucleinopathies may progress and suggest possible therapeutic strategies designed to target α-synuclein. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether the result of the 1‐mg dexamethasone suppression test can predict the improvement of comorbidities after adrenalectomy in patients with subclinical Cushing syndrome. Methods: This retrospective study included 117 subclinical Cushing syndrome patients who underwent adrenalectomy. The numbers of prescribed drugs for metabolic comorbidities and the clinical variables at diagnosis were compared with those at the follow up. Patients were classified into subgroups according to the result of the 1‐mg dexamethasone suppression test. Results: Significant improvements in blood pressure, serum cholesterol and body mass index were observed. Furthermore, a significant improvement in glycated hemoglobin was observed in patients with diabetes mellitus. These improvements led to a discontinuation or reduction of prescribed drugs after surgery. In addition, the greatest reduction of prescribed drugs was observed in patients whose serum cortisol levels were between 1.8 and 3.0 µg/dL after the 1‐mg dexamethasone suppression test. Conclusions: The result of the 1‐mg dexamethasone suppression test can be a useful factor predicting the improvement of comorbidities after adrenalectomy. Current data might give us a new insight into the decision‐making for the treatment of subclinical Cushing syndrome. [ABSTRACT FROM AUTHOR]

Objectives: To identify pre‐treatment factors affecting the duration of post‐surgical steroid replacement in patients undergoing adrenalectomy for subclinical Cushing syndrome. Methods: The present retrospective analysis included 64 patients who underwent unilateral laparoscopic adrenalectomy for subclinical Cushing syndrome. Adrenal tumor and contralateral adrenal sizes together with various clinical factors were studied in association with the duration of post‐surgical steroid replacement. Adrenal tumor and contralateral adrenal size were measured at the level of the maximum transverse plane of the adrenal glands using computed tomography scan or magnetic resonance imaging. Cox's proportional hazards model was used for the statistical analysis. Results: All 64 patients were treated with post‐surgical steroid replacement after adrenalectomy. The median duration of the steroid treatment was 6 months. When assessing the duration of post‐surgical steroid replacement, contralateral adrenal volume <0.745 cm3, contralateral adrenal width <6.15 mm and serum cortisol after a 1‐mg dexamethasone suppression test >2.65 μg/dL were significant predictors of prolonged post‐surgical steroid treatment on univariate analysis. On multivariate analysis, contralateral adrenal width <6.15 mm was the only independent predictive factor for the prolonged post‐surgical steroid replacement. Conclusions: Contralateral adrenal width seems to represent a significant predictive factor for the duration of post‐surgical steroid replacement in subclinical Cushing syndrome patients. Pre‐surgical assessment of image findings might help clinicians determine the total duration of steroid therapy after adrenalectomy. [ABSTRACT FROM AUTHOR]

Background: A functional pituitary adenoma can produce multiple anterior-pituitary hormones, such as growth hormone (GH) -producing adenomas (GHoma) with prolactin or thyrotropin stimulating hormone production in the same lineage. However, it is very rare that acromegaly shows subclinical Cushing's disease (SCD) beyond the lineage. Here we describe the involvement of intratumoral coexistence with 2 types of hormone-producing cells associated with different lineage in acromegaly concomitant with SCD. Case presentation: In our study, we performed clinical evaluation of the patient showing acromegaly with SCD. To elucidate the mechanisms of this pathology, we analyzed immunohistochemistry and gene expression of anterior-pituitary hormones and transcriptional factors in the resected pituitary tumor. On immunohistochemical staining, most of the tumor cells were strongly stained for GH antibody, while some cells were strongly positive for adrenocorticotropic hormone (ACTH). Gene expression analysis of a transsphenoidal surgery sample of the pituitary gland revealed that ACTH-related genes, such as POMC, Tpit, and NeuroD1 mRNA, had higher expression in the tumor tissue than the nonfunctional adenoma but lower expression compared to an adenoma of typical Cushing's disease. Further, double-labeling detection methods with a fluorescent stain for ACTH and GH demonstrated the coexistence of ACTH-positive cells (GH-negative) among the GH-positive cells in the tumor. Additionally, Pit-1 expression was reduced in the ACTH-positive cells from tumor tissue primary culture. Conclusion: Here we described a case of a pituitary tumor diagnosed with acromegaly associated with SCD. We performed quantitative-expression analyses of transcriptional factors of the tumor tissue and immunohistochemistry analysis of tumor-derived primary culture cells, which suggested that the multihormonal pituitary adenoma concomitant with Pit-1 and Tpit lineage cells caused acromegaly associated with SCD. [ABSTRACT FROM AUTHOR]

In recent years, Cu/low-k damascene (buried interconnects) processing, which uses Cu interconnects with low-dielectric-constant (low-k) films, has emerged as a way to satisfy the requirements for making devices ultrasmall, high-speed, and usable in ultralarge-scale integration (ultra-LSI). However, the use of Cu in combination with new materials to make the low-k films has led to difficulties in developing a process for cleaning after post-chemical-mechanical planarization (CMP). One of these problems is the presence of hydrophobic residuals on the low-k films, for whose removal many slurries (polishing agents) and cleaning fluids have been developed. In our work, we have combined these slurries and cleaning fluids, and investigated the effectiveness of the combinations in cleaning low-k films, allowing us to develop an optimum process. We determined the defect counts for TEOS, Cu, and two kinds of low-k films, and measured the level of contamination of the low-k film contaminant by spots of Cu, from which we identified cleaning fluid that performed best. We also confirmed that the performance of the cleaning fluids was different depending on the choice of slurry. We then used our optimum process to formulate a fabrication scheme for devices with the Cu/low-k structure, fabricated a set of devices, and investigated their electrical characteristics. Because of the significant reduction we observed in leakage currents between circuit lines to below 10-9 to 10-10A/m, we argue that our process can be used to fabricate ultra-LSI device ensembles under real conditions. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 89(11): 19–30, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20187 [ABSTRACT FROM AUTHOR]