3H-Spiroperidol (Spiperone) Binding Sites in Rat Adrenal Glomerulosa Cells

3H-spiperone, a dopaminergic antagonist, was used to study binding sites in rat adrenal glomerulosa membrane. The equilibrium dissociation constant (Kd) and binding capacity for 3H-spiperone binding were 2.2 nM and 268 fmol/mg protein, respectively. Determination of the Kd by kinetic studies provided a value of 2.6 nM, which corresponded closely to the Kd estimated by equilibrium studies. In a study of the subcellular distribution of dopamine receptors in adrenal glomerulosa cells, 3H-spiperone binding activity at the interface of density 1.14 to 1.16 accounted for 60% of the total activity in all fractions. These dopaminergic binding sites in adrenal glomerulosa cells may modulate aldosterone secretion induced by antidopaminergic agents

Pericardial Fat Thickness Increases with Greater Burden of Adverse Metabolic Factors Among Adults with Normal-Range Body Mass Index: The Framingham Heart Study

Introduction: Greater burden of pericardial fat is associated with increased body mass index (BMI). Obesity is associated with unfavorable metabolic characteristics such as hypertension, dyslipidemia, and glucose intolerance. We sought to determine whether unfavorable metabolic profile alone, in the absence of excess BMI, was itself associated with increased pericardial fat thickness (PFT). Methods:From the 1,794 Framingham Offspring cohort adults who underwent cardiac magnetic resonance (CMR), we identified 446 free of non-skin cancer and prevalent clinical cardiovascular disease (CVD) who had 18.5≤BMI2and complete covariates. We calculated a metabolic score (MS) based on ATPIII criteria where 1 point was assigned for each of: a) fasting glucose≥100 mg/dL or diabetes; b) SBP≥130 or DBP≥85 mmHg or antihypertensive treatment; c) triglycerides≥150 mg/dL; d) HDL cholesterol \u3c40(M)/ Results: PFT increased with worsening metabolic score at the fixed locations of the apical and mid-level RV, as well as at maximal PFT. On pairwise comparisons, only the MS3+ group had PFT that was consistently significantly greater than that of MS0. Conclusions: In a community-dwelling cohort, among participants who were free of cancer and clinical CVD and had normal-range or BMI, worsening metabolic profile was associated with increased pericardial fat thickness

Atherosclerotic Biomarkers and Aortic Atherosclerosis by Cardiovascular Magnetic Resonance Imaging in the Framingham Heart Study

Background: The relations between subclinical atherosclerosis and inflammatory biomarkers have generated intense interest but their significance remains unclear. We sought to determine the association between a panel of biomarkers and subclinical aortic atherosclerosis in a community‐based cohort. Methods and Results: We evaluated 1547 participants of the Framingham Heart Study Offspring cohort who attended the 7th examination cycle and underwent both cardiovascular magnetic resonance imaging (CMR) and assays for 10 biomarkers associated with atherosclerosis: high‐sensitivity C‐reactive protein, fibrinogen, intercellular adhesion molecule‐1, interleukin‐6, interleukin‐18, lipoprotein‐associated phospholipase‐A2 activity and mass, monocyte chemoattractant protein‐1, P‐selectin, and tumor necrosis factor receptor‐2. In logistic regression analysis, we found no significant association between the biomarker panel and the presence of aortic plaque (global P=0.53). Using Tobit regression with aortic plaque as a continuous variable, we noted a modest association between biomarker panel and aortic plaque volume in age‐ and sex‐adjusted analyses (P=0.003). However, this association was attenuated after further adjustment for clinical covariates (P=0.09). Conclusions: In our community‐based cohort, we found no significant association between our multibiomarker panel and aortic plaque. Our results underscore the strengths and limitations of the use of biomarkers for the identification of subclinical atherosclerosis and the importance of traditional risk factors

Sustained delivery of sphingosine-1-phosphate using poly(lactic-co-glycolic acid)-based microparticles stimulates Akt/ERK-eNOS mediated angiogenesis and vascular maturation restoring blood flow in ischemic limbs of mice

金沢大学医薬保健研究域医学系Therapeutic angiogenesis is a promising strategy for treating ischemia. The lysophospholipid mediator sphingosine-1-phosphate (S1P) acts on vascular endothelial cells to stimulate migration and tube formation, and plays the critical role in developmental angiogenesis. We developed poly(lactic-co-glycolic-acid) (PLGA)-based S1P-containing microparticles (PLGA-S1P), which are biodegradable and continuously release S1P, and studied the effects of PLGA-S1P on neovascularization in murine ischemic hindlimbs. Intramuscular injections of PLGA-S1P stimulated blood flow in C57BL/6 mice dose-dependently, with repeated administrations at a 3-day interval, rather than a single bolus or 6-day interval, over 28. days conferring the optimal stimulating effect. In Balb/c mice that exhibit limb necrosis and dysfunction due to retarded blood flow recovery, injections of PLGA-S1P stimulated blood flow with alleviation of limb necrosis and dysfunction. PLGA-S1P alone did not induce edema in ischemic limbs, and rather blocked vascular endothelial growth factor-induced edema. PLGA-S1P not only increased the microvessel densities in ischemic muscle, but promoted coverage of vessels with smooth muscle cells and pericytes, thus stabilizing vessels. PLGA-S1P stimulated Akt and ERK with increased phosphorylation of endothelial nitric oxide synthase in ischemic muscle. The effects of the nitric oxide synthase inhibitor, Nω-nitro-l-arginine methylester, showed that PLGA-S1P-induced blood flow stimulation was partially dependent on nitric oxide. Injections of PLGA-S1P also increased the expression of angiogenic factors and the recruitment of CD45-, CD11b- and Gr-1-positive myeloid cells, which are implicated in post-ischemic angiogenesis, into ischemic muscle. These results indicate that PLGA-based, sustained local delivery of S1P is a potentially useful therapeutic modality for stimulating post-ischemic angiogenesis. © 2010 Elsevier B.V

Phosphoproteomics-Based Modeling Defines the Regulatory Mechanism Underlying Aberrant EGFR Signaling

BACKGROUND: Mutation of the epidermal growth factor receptor (EGFR) results in a discordant cell signaling, leading to the development of various diseases. However, the mechanism underlying the alteration of downstream signaling due to such mutation has not yet been completely understood at the system level. Here, we report a phosphoproteomics-based methodology for characterizing the regulatory mechanism underlying aberrant EGFR signaling using computational network modeling. METHODOLOGY/PRINCIPAL FINDINGS: Our phosphoproteomic analysis of the mutation at tyrosine 992 (Y992), one of the multifunctional docking sites of EGFR, revealed network-wide effects of the mutation on EGF signaling in a time-resolved manner. Computational modeling based on the temporal activation profiles enabled us to not only rediscover already-known protein interactions with Y992 and internalization property of mutated EGFR but also further gain model-driven insights into the effect of cellular content and the regulation of EGFR degradation. Our kinetic model also suggested critical reactions facilitating the reconstruction of the diverse effects of the mutation on phosphoproteome dynamics. CONCLUSIONS/SIGNIFICANCE: Our integrative approach provided a mechanistic description of the disorders of mutated EGFR signaling networks, which could facilitate the development of a systematic strategy toward controlling disease-related cell signaling

[資料] Ａ看護大学における教職（養護教諭１種）課程の教育の成果と課題 ～第１期生（2018年入学生）の養成から卒業までに着目して～

要旨：　本稿の目的は、A県で唯一となる養護教諭の養成を始めたA看護大学において、どのような教育成果と課題があるのかを教職課程第１期生養成の歩みから探り明らかにし、今後の教職課程の取り組みに活かすことである。　方法として、A看護大学教職課程専門委員会の活動の実際について、①委員会新旧構成員が主に教職課程に関する活動内容を中心に記述し、②A看護大学教職課程修了生へのインタビューにて、教育成果と課題を調査した。　教職課程の課題として、教職課程と看護師課程の学士教育の協働を学部レベル、科目レベルで促進するための協働が今後重要になり、看護大学という特性を考慮した運営が重要となる。また、教員採用試験対策は教職課程を選択する学生と教員さらには県レベル、市町村レベルでの教育委員会との継続した連携体制の構築が重要になると考えられた。教職課程を選択する学生にとっては、看護師課程との両立は実習や講義の過密さの上で厳しいカリキュラムではあるが、養護教諭１種免許の取得は達成感が大きいことが明らかとなった。Abstract:This study aims to explore and clarify the educational achievements and issues at College of Nursing A, which is the only school training nursing teachers in prefecture A, by focusing on the first class of students to improve the overall program.The method used by the new and former members of the nursing teacher education program committee was 1） describing the process of creating the curriculum, and 2） interviewing the program graduates regarding educational achievements and challenges.For issues related to the nursing teacher education program, it will be important to promote cooperation between the nursing teacher education committee and the nursing faculty in terms of courses in the curriculum while addressing competencies required of a nursing college. In addition, it is recommended to collaborate between program students and teachers as well as boards of education at the municipal and prefectural levels to deal with Nursing Teacher Employment Examination preparation. For the nursing teacher education program graduates, taking the additional practical training and classes required to obtain the first-class Yogo Teacher Type 1 license gave a great sense of accomplishment