98 research outputs found

    Gender Studies and Modern Japanese Literature

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    This paper first considers Women\u27s Studies and Gender Studies in Japan. Then I try to explain my research as a case of Gender Studies on Modern Japanese Literature. I am using the name in the Japanese way, the order of the name having the family name first

    Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome

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    Autophagy is a cellular mechanism involved in the bulk degradation of proteins and turnover of organelle. Several studies have shown the significance of autophagy of the renal tubular epithelium in rodent models of tubulointerstitial disorder. However, the role of autophagy in the regulation of human glomerular diseases is largely unknown. The current study aimed to demonstrate morphological evidence of autophagy and its association with the ultrastructural changes of podocytes and clinical data in patients with idiopathic nephrotic syndrome, a disease in which patients exhibit podocyte injury. The study population included 95 patients, including patients with glomerular disease (minimal change nephrotic syndrome [MCNS], n = 41; idiopathic membranous nephropathy [IMN], n = 37) and 17 control subjects who underwent percutaneous renal biopsy. The number of autophagic vacuoles and the grade of foot process effacement (FPE) in podocytes were examined by electron microscopy (EM). The relationships among the expression of autophagic vacuoles, the grade of FPE, and the clinical data were determined. Autophagic vacuoles were mainly detected in podocytes by EM. The microtubule-associated protein 1 light chain 3 (LC3)-positive area was co-localized with the Wilms tumor 1 (WT1)-positive area on immunofluorescence microscopy, which suggested that autophagy occurred in the podocytes of patients with MCNS. The number of autophagic vacuoles in the podocytes was significantly correlated with the podocyte FPE score (r = -0.443, p = 0.004), the amount of proteinuria (r = 0.334, p = 0.033), and the level of serum albumin (r = -0.317, p = 0.043) in patients with MCNS. The FPE score was a significant determinant for autophagy after adjusting for the age in a multiple regression analysis in MCNS patients (p = 0.0456). However, such correlations were not observed in patients with IMN or in control subjects. In conclusion, the results indicated that the autophagy of podocytes is associated with FPE and severe proteinuria in patients with MCNS. The mechanisms underlying the activation of autophagy in association with FPE in podocytes should be further investigated in order to elucidate the pathophysiology of MCNS

    Therapeutic benefits of factors derived from stem cells from human exfoliated deciduous teeth for radiation-induced mouse xerostomia

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    Radiation therapy for head and neck cancers is frequently associated with adverse effects on the surrounding normal tissue. Irreversible damage to radiation-sensitive acinar cells in the salivary gland (SG) causes severe radiation-induced xerostomia (RIX). Currently, there are no effective drugs for treating RIX. We investigated the efficacy of treatment with conditioned medium derived from stem cells from human exfoliated deciduous teeth (SHED-CM) in a mouse RIX model. Intravenous administration of SHED-CM, but not fibroblast-CM (Fibro-CM), prevented radiation-induced cutaneous ulcer formation (p < 0.0001) and maintained SG function (p < 0.0001). SHED-CM treatment enhanced the expression of multiple antioxidant genes in mouse RIX and human acinar cells and strongly suppressed radiation-induced oxidative stress. The therapeutic effects of SHED-CM were abolished by the superoxide dismutase inhibitor diethyldithiocarbamate (p < 0.0001). Notably, quantitative liquid chromatography-tandem mass spectrometry shotgun proteomics of SHED-CM and Fibro-CM identified eight proteins activating the endogenous antioxidant system, which were more abundant in SHED-CM than in Fibro-CM (p < 0.0001). Neutralizing antibodies against those activators reduced antioxidant activity of SHED-CM (anti-PDGF-D; p = 0.0001, anti-HGF; p = 0.003). Our results suggest that SHED-CM may provide substantial therapeutic benefits for RIX primarily through the activation of multiple antioxidant enzyme genes in the target tissue

    Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis

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    Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α, Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes

    Identification of tuberculosis-associated proteins in whole blood supernatant

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    <p>Abstract</p> <p>Background</p> <p>Biological parameters are useful tools for understanding and monitoring complicated disease processes. In this study, we attempted to identify proteins associated with active pulmonary tuberculosis (TB) using a proteomic approach.</p> <p>Methods</p> <p>To assess TB-associated changes in the composition of human proteins, whole blood supernatants were collected from patients with active TB and healthy control subjects. Two-dimensional difference gel electrophoresis (2D-DIGE) was performed to analyze proteins with high molecular weights (approximately >20 kDa). Baseline protein levels were initially compared between patients with active TB and control subjects. Possible changes of protein patterns in active TB were also compared <it>ex vivo </it>between whole blood samples incubated with <it>Mycobacterium tuberculosis </it>(<it>Mtb</it>)-specific antigens (stimulated condition) and under unstimulated conditions. Immunoblot and enzyme-linked immunosorbent assays (ELISA) were performed to confirm differences in identified proteins.</p> <p>Results</p> <p>Under the baseline condition, we found that the levels of retinol-binding protein 4 (RBP4), fetuin-A (also called α-HS-glycoprotein), and vitamin D-binding protein differed between patients with active TB and control subjects on 2D gels. Immunoblotting results confirmed differential expression of RBP4 and fetuin-A. ELISA results further confirmed significantly lower levels of these two proteins in samples from patients with active TB than in control subjects (<it>P </it>< 0.0001). <it>Mtb</it>-specific antigen stimulation <it>ex vivo </it>altered clusterin expression in whole blood samples collected from patients with active TB.</p> <p>Conclusions</p> <p>We identified TB-associated proteins in whole blood supernatants. The dynamics of protein expression during disease progression may improve our understanding of the pathogenesis of TB.</p

    Resting Heart Rate Variability Is Associated With Subsequent Orthostatic Hypotension: Comparison Between Healthy Older People and Patients With Rapid Eye Movement Sleep Behavior Disorder.

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    Background:Orthostatic hypotension (OH) caused by autonomic dysfunction is a common symptom in older people and patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). The orthostatic challenge test is a standard autonomic function test that measures a decrease of blood pressure during a postural change from supine to standing positions. Although previous studies have reported that changes in heart rate variability (HRV) are associated with autonomic dysfunction, no study has investigated the relationship between HRV before standing and the occurrence of OH in an orthostatic challenge test. This study aims to examine the connection between HRV in the supine position and the occurrence of OH in an orthostatic challenge test.Methods:We measured the electrocardiograms of patients with iRBD and healthy older people during an orthostatic challenge test, in which the supine and standing positions were held for 15 min, respectively. The subjects were divided into three groups: healthy controls (HC), OH-negative iRBD [OH (–) iRBD], and OH-positive iRBD [OH (+) iRBD]. HRV measured in the supine position during the test were calculated by time-domain analysis and Poincaré plots to evaluate the autonomic dysfunction.Results:Forty-two HC, 12 OH (–) iRBD, and nine OH (+) iRBD subjects were included. HRV indices in the OH (–) and the OH (+) iRBD groups were significantly smaller than those in the HC group. The multivariate logistic regression analysis for OH identification for the iRBD groups showed the model whose inputs were the HRV indices, i.e., standard deviation 2 (SD2) and the percentage of adjacent intervals that varied by more than 50 ms (pNN50), had a receiver operating characteristic curve with area under the curve of 0.840, the sensitivity to OH (+) of 1.000, and the specificity to OH (–) of 0.583 (p = 0.023).Conclusions:This study showed the possibility that short-term HRV indices in the supine position would predict subsequent OH in iRBD patients. Our results are of clinical importance in terms of showing the possibility that OH can be predicted using only HRV in the supine position without an orthostatic challenge test, which would improve the efficiency and safety of testing
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