Tagawa A.,Shiga University of Medical Science |
Yasuda M.,Shiga University of Medical Science |
Kume S.,Shiga University of Medical Science |
Yamahara K.,Shiga University of Medical Science |
And 16 more authors.
Diabetes | Year: 2016
Overcoming refractory massive proteinuria remains a clinical and research issue in diabetic nephropathy. This study was designed to investigate the pathogenesis of massive proteinuria in diabetic nephropathy, with a special focus on podocyte autophagy, a system of intracellular degradation that maintains cell and organelle homeostasis, using human tissue samples and animal models. Insufficient podocyte autophagy was observed histologically in patients and rats with diabetes and massive proteinuria accompanied by podocyte loss, but not in those with no or minimal proteinuria. Podocyte-specific autophagy-deficient mice developed podocyte loss and massive proteinuria in a high-fat diet (HFD)-induced diabetic model for inducing minimal proteinuria. Interestingly, huge damaged lysosomes were found in the podocytes of diabetic rats with massive proteinuria and HFD-fed, podocyte-specific autophagy-deficient mice. Furthermore, stimulation of cultured podocytes with sera from patients and rats with diabetes and massive proteinuria impaired autophagy, resulting in lysosome dysfunction and apoptosis. These results suggest that autophagy plays a pivotal role in maintaining lysosome homeostasis in podocytes under diabetic conditions, and that its impairment is involved in the pathogenesis of podocyte loss, leading to massive proteinuria in diabetic nephropathy. These results may contribute to the development of a new therapeutic strategy for advanced diabetic nephropathy. © 2016 by the American Diabetes Association. Source
Hashii Y.,Osaka University |
Kusuki S.,National Hospital Organization Osaka National Hospital |
Takizawa S.,Ikeda City Hospital |
Tokimasa S.,Osaka City University |
And 3 more authors.
Pediatrics International | Year: 2014
Background Micafungin, an antifungal echinocandin, has been indicated for pediatric patients with invasive fungal infection (IFI) in Japan and Europe. Its efficacy in immunocompromised pediatric patients with IFI, however, has not been fully investigated.Methods The safety and efficacy of micafungin as an antifungal therapy were analyzed in nine consecutive severe immunocompromised patients with IFI.Results Three patients with proven or probable Candida infections had complete response to micafungin therapy. Of the other six patients with proven, probable or possible Aspergillus infection, four had complete response and one had partial response to micafungin treatment. No severe adverse events were observed.Conclusions In this small series, micafungin was effective for IFI caused by both Candida and Aspergillus species and no severe adverse events were observed in these immunocompromised patients. © 2014 Japan Pediatric Society. Source
Analysis of late toxicity associated with external beam radiation therapy for prostate cancer with uniform setting of classical 4-field 70 Gy in 35 fractions: A survey study by the Osaka Urological Tumor Radiotherapy Study Group
Yoshioka Y.,Osaka University |
Suzuki O.,Japan National Cardiovascular Center Research Institute |
Nishimura K.,Japan National Cardiovascular Center Research Institute |
Inoue H.,Ikeda City Hospital |
And 6 more authors.
Journal of Radiation Research | Year: 2013
We aimed to analyse late toxicity associated with external beam radiation therapy (EBRT) for prostate cancer using uniform dose-fractionation and beam arrangement, with the focus on the effect of 3D (CT) simulation and portal field size. We collected data concerning patients with localized prostate adenocarcinoma who had been treated with EBRT at five institutions in Osaka, Japan, between 1998 and 2006. All had been treated with 70 Gy in 35 fractions, using the classical 4-field technique with gantry angles of 0°, 90°, 180° and 270°. Late toxicity was evaluated strictly in terms of the Common Terminology Criteria for Adverse Events Version 4.0. In total, 362 patients were analysed, with a median follow-up of 4.5 years (range 1.0-11.6). The 5-year overall and cause-specific survival rates were 93% and 96%, respectively. The mean ± SD portal field size in the right-left, superior-inferior, and anterior-posterior directions was, respectively, 10.8 ± 1.1, 10.2 ± 1.0 and 8.8 ± 0.9 cm for 2D simulation, and 8.4 ± 1.2, 8.2 ± 1.0 and 7.7 ± 1.0 cm for 3D simulation (P < 0.001). No Grade 4 or 5 late toxicity was observed. The actuarial 5-year Grade 2-3 genitourinary and gastrointestinal (GI) late toxicity rates were 6% and 14%, respectively, while the corresponding late rectal bleeding rate was 23% for 2D simulation and 7% for 3D simulation (P < 0.001). With a uniform setting of classical 4-field 70 Gy/35 fractions, the use of CT simulation and the resultant reduction in portal field size were significantly associated with reduced late GI toxicity, especially with less rectal bleeding. © The Author 2012. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Therapeutic Radiology and Oncology. Source
Mizushima T.,Osaka University |
Tamagawa H.,Otemae Hospital |
Matsuda C.,Osaka General Medical Center |
Murata K.,Suita Municipal Hospital |
And 13 more authors.
Oncology (Switzerland) | Year: 2015
Background/Objective: Oral tegafur/uracil and leucovorin (UFT/LV) therapy is effective and safe for elderly patients with advanced or metastatic colorectal cancer (CRC). However, there are few studies on the combination of bevacizumab with UFT/LV. This clinical study evaluated the efficacy and safety of UFT/LV plus bevacizumab as a first-line therapy for elderly patients with advanced or metastatic CRC. Methods: Forty patients with advanced or metastatic CRC aged ≥75 years were enrolled in this multicenter, open-label, single-arm phase II study. All patients received oral UFT (300-600 mg) and LV (50 mg) twice daily on days 1-21 and intravenous bevacizumab (5 mg/kg) on days 1 and 15 of a 4-week cycle (University Hospital Medical Information Network No. UMIN000003447). Results: The median follow-up period was 14.7 months. The response rate was 20.0% [95% confidence interval (CI): 9.1-35.6], median progression-free survival was 8.9 months (95% CI: 5.3-11), and median overall survival was 21.7 months (95% CI: 13.7-23.4). The only grade 3 hematological toxicity was neutropenia (3.0%), and the incidence rates of grade 3 nonhematological toxicity were low at ≤10%. Conclusion: UFT/LV plus bevacizumab is a promising first-line regimen for elderly patients with advanced or metastatic CRC. The combination is well tolerated and efficacious. © 2015 S. Karger AG, Basel. Source
Maeda L.,Nishinomiya Municipal Central Hospital |
Maeda L.,Osaka University |
Ono M.,Ikeda City Hospital |
Koyama T.,Kyoritsu Neurosurgery Hospital |
And 4 more authors.
Journal of Anesthesia | Year: 2011
Purpose: The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). Methods: Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain activation in response to mechanical nociceptive stimulation targeting muscle and bone were measured by fMRI and analyzed. Results: Painful mechanical stimulation targeting muscle and bone activated the common areas including bilateral insula, anterior cingulate cortex, posterior cingulate cortex, secondary somatosensory cortex (S2), inferior parietal lobe, and basal ganglia. The contralateral S2 was more activated by strong stimulation than by weak stimulation. Some areas in the basal ganglia (bilateral putamen and caudate nucleus) were more activated by muscle stimulation than by bone stimulation. Conclusions: The putamen and caudate nucleus may have a more significant role in brain processing of muscle pain compared with bone pain. © 2011 Japanese Society of Anesthesiologists. Source