Immunohistochemical analysis of tau phosphorylation and astroglial activation with enhanced leptin receptor expression in diet-induced obesity mouse hippocampus

AbstractAccumulating evidence indicates that obesity is an independent risk factor for developing Alzheimer disease (AD). Recent studies have shown that diet-induced obesity (DIO) enhances AD-related pathologies in transgenic mouse models of the disease. DIO increases amyloid β (Aβ) deposition in amyloidogenic transgenic mice and enhances tau phosphorylation in tau transgenic mice. However, it remains unclear whether DIO also enhances AD-related pathological processes in wild-type (WT) mice. In this study, we examined the effects of DIO on Aβ and tau pathology in WT mice using immunohistochemistry. In addition, we evaluated the protective effect of voluntary exercise on the DIO-induced pathological changes. DIO caused tau phosphorylation and astroglial activation in the hippocampus in WT mice. Interestingly, these changes were associated with enhanced astrocytic leptin receptor (LepR) expression and mild microgliosis, but not Aβ accumulation. Although phosphorylated tau staining was only observed in the hippocampus, astrogliosis and microgliosis were present in both the amygdala and hippocampus. However, no apparent neuronal loss was observed. Voluntary exercise prevented these DIO-induced pathological changes. Our results demonstrate for the first time that DIO causes tau phosphorylation and that astrocytic LepR might be involved in the pathological process in WT mouse hippocampus. Our findings also suggest that physical exercise is a promising strategy for the prevention of AD in patients with obesity

Mott insulating state in a quarter-filled two-orbital Hubbard chain with different bandwidths

We investigate the ground-state properties of the one-dimensional two-band Hubbard model with different bandwidths. The density-matrix renormalization group method is applied to calculate the averaged electron occupancies $n$ as a function of the chemical potential $\mu$. Both at quarter and half fillings, "charge plateaux" appear in the $n$-$\mu$ plot, where $d\mu/dn$ diverges and the Mott insulating states are realized. To see how the orbital polarization in the one-quarter charge plateau develops, we apply the second-order perturbation theory from the strong-coupling limit at quarter filling. The resultant Kugel-Khomskii spin-orbital model includes a $magnetic$ field coupled to orbital pseudo-spins. This field originates from the discrepancy between the two bandwidths and leads to a finite orbital pseudo-spin magnetization.Comment: 4 pages, 2 figures, Proceedings of LT2

アタラシイ エイゾウ キョウザイ ノ カイハツ オ メザシテ : ガクシュウシャ ノ センモン ニ ハイリョ シタ ジュギョウ ノ ココロミ

医学・歯学・薬学系の学部および大学院に所属している日本語学習者を対象にしたクラスで，留学生が専門分野の日本語によりアクセスしやすくなる効果を期待して，医・科学系の映像素材を使った教材を作成し，授業実践を試みた。実施後の調査では，映像を使用した授業に対する興味・関心は高かったものの，内容は必ずしも医・科学系の映像でなくてもよいという反応も見られた。教師の振り返りでは，教材の選定と作成とに多くの手間と時間がかかることがわかった。今後はこの結果を踏まえ，より学生のニーズに合った，日本語の運用能力を伸ばす教材の開発が必要であろう

Improved Recovery of Exfoliated Colonocytes from Feces Using Newly Developed Immunomagnetic Beads

We demonstrated the feasibility of a new methodology for isolating colonocytes from feces. To reduce costs and improve the recovery rate of colonocytes from feces, we attempted to develop new immunomagnetic beads. Several sizes of magnetic beads were prepared and tagged with a monoclonal antibody against EpCAM. We made several new monoclonal antibodies against EpCAM, and each monoclonal antibody was tagged to the magnetic beads. In the simulation, the most efficient recovery of HT-29 cells was obtained using the smallest size of beads. Also, beads tagged with a monoclonal antibody with a higher affinity against EpCAM had a higher recovery rate. Similar results were obtained when the smallest size of beads with the highest-affinity monoclonal antibody was applied to clinical samples. The newly developed immunomagnetic beads may be useful for isolating colorectal cancer cells from feces, enabling the cytological or molecular biological diagnosis of CRC

Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone

BACKGROUND: Giant cell tumors (GCTs) of bone are primary benign bone tumors that are characterized by a high number of osteoclast-like multinuclear giant cells (MNCs). Recent studies suggest that the spindle-shaped stromal cells in GCTs are tumor cells, while monocyte-like cells and MNCs are reactive osteoclast precursor cells (OPCs) and osteoclasts (OCs), respectively. In this study, we investigated the pathogenesis of osteoclastic bone destruction in GCTs by focusing on the role of the vascular endothelial growth factor (VEGF)-Flt-1 (type-1 VEGF receptor)-focal adhesion kinase (FAK) pathway. METHODS: The motility of OPCs cells was assessed by a chemotaxis assay and the growth of OPCs was examined using a cell proliferation assay. The expression of VEGF and activation of Flt-1 and FAK in clinical GCT samples and in OPCs were detected by immunohistochemistry and immunoblotting. The correlation between the expression levels of activated Flt-1 and FAK and clinical stages of GCTs was investigated by immunohistochemistry. RESULTS: In GCT samples, CD68, a marker of OPCs and OCs, co-localized with Flt-1. Conditioned media from GCT tissue (GCT-CM) enhanced the chemotaxis and proliferation of OPCs. GCT-CM also stimulated FAK activation in OPCs in vitro. Moreover, there was a correlation between the clinical stage of GCTs and the expression of tyrosine-phosphorylated Flt-1 and FAK. CONCLUSIONS: Our results suggest that the VEGF-Flt-1-FAK pathway is involved in the pathogenesis of bone destruction of GCTs

Pulmonary Hypertension in a Patient with Essential Thrombocythemia

A 67-year-old woman with essential thrombocythemia (ET) developed acute heart failure and marked pulmonary hypertension (PH). No clear cause for the PH could be initially found. We suspected that thrombocytosis might cause PH. Treatments with anticoagulant (heparin and warfarin), platelet- lowering (hydroxyurea), and antiplatelet (ticlopidine) agents resulted in improvement of the clinical, hemodynamic conditions, and the control of platelet counts. We found that the main etiology of PH in the present case might be the pulmonary capillary obstruction from local pulmonary microthrombosis complicated with ET. Although PH associated with ET is uncommon, it should be always considered as a possible cause of dyspnea in patients with ET

The prognosis of patients with coronary artery disease complicated by postload hyperinsulinemia

Background: The long-term prognosis of coronary artery disease (CAD) patients with insulin resistance has not been fully examined. In this study, we investigated the influence of postload hyperinsulinemia (PHI) after a 75-g oral glucose tolerance test (OGTT), on the long-term prognosis of CAD patients. Methods: All study patients were diagnosed as having CAD by coronary angiography. The OGTT was performed for all patients to establish their blood glucose. Measurement of serum insulin was also performed simultaneously. Patients with 2-h insulin level of ?. 64. mU/l after the OGTT were included in the postload hyperinsulinemia (PHI) group, and the others were included in the non-PHI group. The prognosis of 208 patients (96 from the PHI group and 112 from the non-PHI group) was retrospectively investigated. Study end points were the composite of death from any cause, unexpected hospitalization for heart failure, new-onset ACS, angina pectoris requiring PCI or CABG, cerebrovascular disease (CVD), and peripheral artery disease (PAD). Variables were compared using Kaplan-Meier analysis and the log-rank tests. Results: The mean follow-up period was 78.7. months. Cardiovascular events including death were 40.6% in the PHI group and 23.2% in the non-PHI group (log-rank p = 0.0144). CVD, PCI, and CABG occurred continuously from early to late stage of follow-up in the PHI group compared with the non-PHI group. Conclusions: The present study showed that the prognosis of CHD patients with PHI was poor. Thus, it is important to pay attention to these conditions for improving the prognosis of CAD patients