Definite ECRS diagnosis with systemic steroid

According to JESREC criteria, definite eosinophilic chronic rhinosinusitis (ECRS) is postoperatively diagnosed based on over 70 eosinophils in high power magnification fields of the resected nasal polyps in patients with probable ECRS. Preoperative systemic administration with steroid is a standard practice, because it reduced intraoperative bleeding during endoscopic sinus surgery (ESS) in patients with ECRS. However, it was recently reported that systemic administration with steroid decreased the number of eosinophils in the nasal polyps, leading to a false negative diagnosis of definite ECRS. To overcome the risk, we have adopted short-term pre-operative systemic administration with low-dose of steroid and examined if our steroid administration makes a false-negative diagnosis. We performed a retrospective chart review of 42 patients with probable ECRS. Eleven patients were administered with 0.5 mg of bethametasone for 7 days before ESS, and other 31 patients were not administered. The average number of eosinophils in nasal polyps in patients who were administered with steroid was 188 ± 167, which was not different from 199 ± 149 in the patients who were not administered. These findings suggest that short-term preoperative administration with low-dose of steroid has few risk of a false-negative diagnosis of definite ECRS

Heart Failure-Inducible Gene Therapy Targeting Protein Phosphatase 1 Prevents Progressive Left Ventricular Remodeling

BACKGROUND: The targeting of Ca(2+) cycling has emerged as a potential therapy for the treatment of severe heart failure. These approaches include gene therapy directed at overexpressing sarcoplasmic reticulum (SR) Ca(2+) ATPase, or ablation of phospholamban (PLN) and associated protein phosphatase 1 (PP1) protein complexes. We previously reported that PP1β, one of the PP1 catalytic subunits, predominantly suppresses Ca(2+) uptake in the SR among the three PP1 isoforms, thereby contributing to Ca(2+) downregulation in failing hearts. In the present study, we investigated whether heart-failure-inducible PP1β-inhibition by adeno-associated viral-9 (AAV9) vector mediated gene therapy is beneficial for preventing disease progression in genetic cardiomyopathic mice. METHODS: We created an adeno-associated virus 9 (AAV9) vector encoding PP1β short-hairpin RNA (shRNA) or negative control (NC) shRNA. A heart failure inducible gene expression system was employed using the B-type natriuretic protein (BNP) promoter conjugated to emerald-green fluorescence protein (EmGFP) and the shRNA sequence. AAV9 vectors (AAV9-BNP-EmGFP-PP1βshRNA and AAV9-BNP-EmGFP-NCshRNA) were injected into the tail vein (2×10(11) GC/mouse) of muscle LIM protein deficient mice (MLPKO), followed by serial analysis of echocardiography, hemodynamic measurement, biochemical and histological analysis at 3 months. RESULTS: In the MLPKO mice, BNP promoter activity was shown to be increased by detecting both EmGFP expression and the induced reduction of PP1β by 25% in the myocardium. Inducible PP1βshRNA delivery preferentially ameliorated left ventricular diastolic function and mitigated adverse ventricular remodeling. PLN phosphorylation was significantly augmented in the AAV9-BNP-EmGFP-PP1βshRNA injected hearts compared with the AAV9-BNP-EmGFP-NCshRNA group. Furthermore, BNP production was reduced, and cardiac interstitial fibrosis was abrogated at 3 months. CONCLUSION: Heart failure-inducible molecular targeting of PP1β has potential as a novel therapeutic strategy for heart failure

人総研シンポジウム抄録 : 福島原発事故12年の経験から学ぶ -当時小学生だった若者達との対話から(第2回)-

departmental bulletin pape

Speciation, Luminescence, and Alkaline Fluorescence Quenching of 4-(2-methylbutyl)aminodipicolinic acid (H2MEBADPA)

4-(2-Methylbutyl)aminodipicolinic acid (H2MEBADPA) has been synthesized and fully characterized in terms of aqueous phase protonation constants (pKa\u27s) and photophysical measurements. The pKa\u27s were determined by spectrophotometric titrations, utilizing a fully sealed titration system. Photophysical measurements consisted of room temperature fluorescence and frozen solution phosphorescence as well as quantum yield determinations at various pH, which showed that only fully deprotonated MEBADPA2– is appreciably emissive. The fluorescence of MEBADPA2– has been determined to be quenched by hydroxide and methoxide anions, most likely through base-catalyzed excited-state tautomerism or proton transfer. This quenching phenomenon has been quantitatively explored through steady-state and time-resolved fluorescence measurements. Utilizing the determined pKas and quenching constants, the fluorescent intensity of MEBADPA2– has been successfully modeled as a function of pH