37 research outputs found
A Case of Rapidly Progressive Diabetic Nephropathy Induced by Osimertinib
The number of patients with diabetic nephropathy is increasing worldwide and it is important to understand the underlying pathological mechanisms of the disease. In early stage diabetic nephropathy, the hyperglycemic environment leads to vascular endothelial cell damage, resulting in overexpression of vascular endothelial growth factor (VEGF) in podocytes and renal pathology of glomerular hypertrophy, glomerular basement membrane thickening, and mesangial hyperplasia. In diabetic nephropathy, renal thrombotic microangiopathy (TMA) develops and the nephropathy progressively worsens in some cases of severe glomerular podocyte damage. Further, receptor tyrosine kinase inhibitors (RTKIs) may suppress VEGF secretion via VEGF receptor-2 tyrosine kinase inhibition in podocytes, which results in renal TMA and rapid deterioration of diabetic nephropathy. Osimertinib, a third-generation irreversible epidermal growth factor receptor (EGFR)-TKI, is approved as a first-line treatment agent for metastatic or locally advanced EGFR mutation-positive non-small cell lung cancer. We encountered a case of a patient with diabetic nephropathy with lung adenocarcinoma treated with osimertinib, whose condition deteriorated from early nephropathy to end-stage renal disease in approximately 4 months. The patient had early diabetic nephropathy, but the use of a RTKI suppressed VEGF expression in podocytes, resulting in the induction of renal TMA and the development of rapidly progressive diabetic nephropathy
Improved long-term performance of pulsatile extracorporeal left ventricular assist device
SummaryBackground and purposeThe majority of heart transplant (HTx) candidates require left ventricular assist device (LVAD) support for more than 2 years before transplantation in Japan. However, the only currently available device is the extracorporeal pulsatile LVAD. The long-term management of extracorporeal LVAD support has improved remarkably over the years. To determine which post-operative management factors are related to the long-term survival of patients on such LVAD, we retrospectively compared the incidence of complications and their management strategies between the initial and recent eras of LVAD use, classified by the year of LVAD surgery.MethodsSixty-nine consecutive patients supported by extracorporeal pulsatile LVAD as a bridge to HTx between 1994 and 2007 were reviewed retrospectively. The patients were assigned according to the time of LVAD surgery to either group A (n=30; between 1994 and 2000) or group B (n=39; between 2001 and 2007).ResultsPatients in group B survived significantly longer on LVAD support than those in group A (674.6 vs. 369.3 days; p<0.001). The 1- and 2-year survival rates were significantly higher in group B than that in group A (82% vs. 48%, p<0.0001; 68% vs. 23%, p<0.0001, respectively). The proportion of deaths due to cerebrovascular accidents was lower (17% vs. 50%, p<0.001) in group B compared with group A. The incidences of systemic infection were similar in both groups, but the proportions of patients alive and achieving transplant surgery after systemic infection were higher in group B than those in group A (55% vs. 14%, p<0.01; 14% vs. 36%, p<0.05, respectively).ConclusionsThe long-term survival of patients even on āfirst-generationā extracorporeal LVAD has improved significantly in the recent era. Careful management of cerebrovascular accidents and systemic infection will play important roles in the long-term LVAD management
Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis
Jun Ueda, Akihito Harada, Takashi Urahama, Shinichi Machida, Kazumitsu Maehara, Masashi Hada, Yoshinori Makino, Jumpei Nogami, Naoki Horikoshi, Akihisa Osakabe, Hiroyuki Taguchi, Hiroki Tanaka, Hiroaki Tachiwana, Tatsuma Yao, Minami Yamada, Takashi Iwamoto, Ayako Isotani, Masahito Ikawa, Taro Tachibana, Yuki Okada, Hiroshi Kimura, Yasuyuki Ohkawa, Hitoshi Kurumizaka, Kazuo Yamagata, Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis, Cell Reports, Volume 18, Issue 3, 2017, Pages 593-600, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2016.12.065
Diagnostic criteria for acute-onset type 1 diabetes mellitus (2012): Report of the Committee of Japan Diabetes Society on the Research of Fulminant and Acute-onset Type 1 Diabetes Mellitus
Type 1 diabetes is a disease characterized by destruction of pancreatic Ī²-cells, which leads to absolute deficiency of insulin secretion. Depending on the manner of onset and progression, it is classified as fulminant, acute-onset or slowly progressive type 1 diabetes. Here, we propose the diagnostic criteria for acute-onset type 1 diabetes mellitus. Among the patients who develop ketosis or diabetic ketoacidosis within 3 months after the onset of hyperglycemic symptoms and require insulin treatment continuously after the diagnosis of diabetes, those with anti-islet autoantibodies are diagnosed with \u27acute-onset type 1 diabetes mellitus (autoimmune)\u27. In contrast, those whose endogenous insulin secretion is exhausted (fasting serum C-peptide immunoreactivity <0.6 ng/mL) without verifiable anti-islet autoantibodies are diagnosed simply with \u27acute-onset type 1 diabetes mellitus\u27. Patients should be reevaluated after certain periods in case their statuses of anti-islet autoantibodies and/or endogenous insulin secretory capacity are unknown
Insulin-producing cells derived from āinduced pluripotent stem cellsā of patients with fulminant type 1 diabetes: vulnerability to cytokine insults and increased expression of apoptosis-related genes
Aims/Introduction: The present study was carried out to generate induced pluripotent stem cells (iPSCs) from patients with fulminant type 1 diabetes, and evaluate the cytokineāinduced apoptotic reactions of Ī²ālike insulināproducing cells differentiated from the iPSCs.Materials and Methods: iPSCs were generated from fibroblasts of patients with fulminant type 1 diabetes by inducing six reprogramming factors. Insulināproducing cells were differentiated from the iPSCs in vitro. The proportion of cleaved caspaseā3āpositive or terminal deoxynucleotidyl transferase 2ā²ādeoxyuridine, 5ā²ātriphosphate nick end labelingāpositive cells among insulin (INS)āpositive cells derived from fulminant type 1 diabetes iPSC and control human iPSC lines was evaluated under treatment with tumor necrosis factorāĪ±, interleukinā1Ī² and interferonāĪ³. Ribonucleic acid sequencing was carried out to compare gene expressions in INSāpositive cells derived from fulminant type 1 diabetes iPSC and control human iPSC lines.Results: Two iPSC clones were established from each of three patients with fulminant type 1 diabetes. The differentiation of insulināproducing cells from fulminant type 1 diabetes iPSC was confirmed by immunofluorescence analysis and KClāinduced Cāpeptide secretion. After treatment with proāinflammatory cytokines, these INSāpositive cells showed higher expression of cleaved caspaseā3 than those derived from control human iPSCs. Altered expression levels of several apoptosisārelated genes were observed in INSāpositive cells derived from the fulminant type 1 diabetes iPSCs by ribonucleic acid sequencing.Conclusions: We generated iPSCs from patients with fulminant type 1 diabetes and differentiated them into insulināproducing cells. This in vitro disease model can be used to elucidate the disease mechanisms of fulminant type 1 diabetes
Aggregated transfer function for smart grid FastADR feedback control of wide area distributed building facilities
Photoinduced Electron Transfer of ZnSāAgInS<sub>2</sub> Solid-Solution Semiconductor Nanoparticles: Emission Quenching and Photocatalytic Reactions Controlled by Electrostatic Forces
The electron transfer between the
fluorescent ZnSāAgInS<sub>2</sub> solid-solution (ZAIS) nanoparticles
(NPs) and redox species
is investigated in an aqueous solution in terms of chemosensors and
photocatalysts. In a case where the ZAIS NPs and quenchers are oppositely
charged, very efficient photoluminescence (PL) quenching (<i>K</i><sub>S</sub> ā 10<sup>6</sup> M<sup>ā1</sup>) is observed because of the specific adsorption of quenchers on
particles. The quenching magnitude increases with the potential gap
between the photoexcited NPs and quenchers. Methyl viologen (MV<sup>2+</sup>) shows the largest quenching behavior; i.e., it is revealed
to quench most of PL by the adsorption of only a single molecule.
In such a case, the linearity of quenching magnitude is lost, and
distribution of the quencher adsorption on NPs should be considered
to clarify the quenching mechanism. In the opposite case where both
the ZAIS NPs and quenchers are negatively charged, although the quenching
efficiency is two to three orders of magnitude lower than that in
the aforementioned adsorption case, electron transfer occurs from
the NPs to redox species. The efficiency of photoreduction is investigated
in association with the charge repulsion between both species