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Proteinuria is a central component of chronic kidney disease and an independent risk factor for cardiovascular disease. Kidney podocytes have an essential role as a filtration barrier against proteinuria. Kruppel-like Factor 4 (KLF4) is expressed in podocytes and decreased in glomerular diseases leading to methylation of the nephrin promoter, decreased nephrin expression and proteinuria. Treatment with an angiotensin receptor blocker (ARB) reduced methylation of the nephrin promoter in murine glomeruli of an adriamycin nephropathy model with recovery of KLF4 expression and a decrease in albuminuria. In podocyte-specific KLF4 knockout mice, the effect of ARB on albuminuria and the nephrin promoter methylation was attenuated. In cultured human podocytes, angiotensin II reduced KLF4 expression and caused methylation of the nephrin promoter with decreased nephrin expression. In patients, nephrin promoter methylation was increased in proteinuric kidney diseases with decreased KLF4 and nephrin expression. KLF4 expression in ARB-treated patients was higher in patients with than without ARB treatment. Thus, angiotensin II can modulate epigenetic regulation in podocytes and ARB inhibits these actions in part via KLF4 in proteinuric kidney diseases. This study provides a new concept that renin-angiotensin system blockade can exert therapeutic effects through epigenetic modulation of the kidney gene expression.

Summary: Altered DNA methylation plays an important role in the onset and progression of kidney disease. However, little is known about how the changes arise in disease states. Here, we report that KAT5-mediated DNA damage repair is essential for the maintenance of kidney podocytes and is associated with DNA methylation status. Podocyte-specific KAT5-knockout mice develop severe albuminuria with increased DNA double-strand breaks (DSBs), increased DNA methylation of the nephrin promoter region, and decreased nephrin expression. Podocyte KAT5 expression is decreased, whereas DNA DSBs and DNA methylation are increased in diabetic nephropathy; moreover, KAT5 restoration by gene transfer attenuates albuminuria. Furthermore, KAT5 decreases DNA DSBs and DNA methylation at the same nephrin promoter region, which indicates that KAT5-mediated DNA repair may be related to DNA methylation status. These results suggest a concept in which an environment of DNA damage repair, which occurs with decreased KAT5, may affect DNA methylation status. : Hishikawa et al. reveal that KAT5-mediated DNA repair is essential for podocyte maintenance and is related to changes in DNA methylation status. Decreased podocyte KAT5 expression may contribute to the pathophysiology of diabetic nephropathy, suggesting a therapeutic target. Keywords: podocyte, DNA damage repair, DNA methylation, diabetic nephropathy

Background Acute aortic dissection (AAD) is often missed on initial assessment. Purpose The aim of our study was to identify features associated with misdiagnosis of AAD. Methods and results We examined a total of 109 emergency room (ER) patients who were ultimately diagnosed with AAD. Misdiagnosis of AAD was defined as failure to diagnose AAD at the end of the initial assessment in the ER, and occurred in 17 patients (16%). The alternate diagnosis consisted of acute coronary syndrome (n = 10), other cardiovascular disease (n = 3), abdominal disease (n = 3), and cerebral infarction (n = 1). In the misdiagnosed patients, walk-in mode of admission to the ER (29% vs. 10%, p = 0.042) and anterior chest pain (71% vs. 41%, p = 0.025) were more frequent, and widened mediastinum (25% vs. 55%, p = 0.023) was less frequent than in diagnosed patients. The number of imaging studies performed per patient was also fewer in misdiagnosed patients than in diagnosed patients (0.82 ± 0.81 vs. 1.53 ± 0.52, p

The catalytic methanol steam reforming reaction was investigated by numerical simulation and experiments. Methanol conversion ratio as well as carbon monoxide (CO), which poisons a typical polymer electrolyte fuel cell, increases in a tablet catalyst when temperature is elevated. There is a trade-off relationship between methanol conversion ratio and CO concentration. It was found that the reforming reaction is controlled by heat transfer at large methanol flow rate, where the trade-off relationship shifts to lower methanol conversion ratio and higher CO concentration. To improve the trade-off relationship, internal corrugated metal heater and external catalytic combustion heater were applied to enhance the heat transfer. Optimal cell density for the internal corrugated metal heater, which was about 9×10 5 cell/m 2 , was closely related with reaction parameters such as velocity, cell density, geometric surface area and hydraulic diameter. The catalytic combustion heater is larger than the internal corrugated metal heater in size. Both high methanol conversion ratio and low CO concentration were accomplished by heat transfer enhancement with the two techniques at large methanol flow rate.

This paper reports on the development of key components, specifications, configuration and operating characteristics of a hydrogen-fueled portable power source with polymer electrolyte fuel cell (PEFC). A 1 kW class fuel cell module operating on an exclusive method of internal humidification was developed for the power source. A dc–ac inverter, in which a general-purpose integrated power module (IPM) was used as a switching device for microprocessor-based power conversion control, was developed to save the cost of generating dc power output from the cell module. The power source supplies full power within 2 min from start-up, and is capable of generating rated 1 kW power for about 3 h and even longer if the cylinders are replaced. This power source has been confirmed to offer a high power generation efficiency of 30% or higher in overall output range, yielding good-quality power with little noise.

A sinterable LaCr0.75Mg0.25O3 powder consisting of submicrometer-size particles ( 3.17×10 3 S m −1 at 1000°C. Their thermal expansion coefficient is 10.1×10 −6 /° C .

Sinterable LaCrO 3 powder consisting of submicron particles (≈0.2 μm) has been obtained at low temperatures (≈850°C) by decomposition of LaCrO 4 , which crystallizes at 495°C, from an amorphous material prepared by the hydrazine method. Powder characterization is examined. Dense LaCrO 3 ceramics (93.9% of theoretical) with small grains (≈2.1 μm) can be fabricated by sintering for 2 h at 1600°C without any control of oxygen pressure. They show a high electrical conductivity of 108 S·m −1 at 1000°C.

The chemical state of oxygen in Ag + /Na + ion-exchanged sodium silicate glass was investigated using X-ray photoelectron spectroscopy and 29 Si nuclear magnetic resonance spectroscopy. Ion-exchange treatment was performed on 34Na 2 O-66SiO 2 glass at temperatures well below T g of the mother glass, giving glass samples with various Ag + /Na + ratios. The glass transition temperature decreased about 150 K with increase in Ag + concentration, accompanied by the simultaneous decrease of the thermal expansion coefficient by about 50%. Large changes in Ols XPS spectra were observed; the bridging and non-bridging oxygen peaks shifted toward larger binding energies, and the ratio of non-bridging oxygen (NBO) to bridging oxygen decreased with increasing Ag + concentration. This trend revealed that the increased covalency of Ag + -O nb bonds decreased T g and the thermal expansion coefficients. 29 Si-NMR results showed that Q 3 units decreased while Q 2 units increased without accompanying Q 4 units. These results suggested that two coordinated Ag + ions with non-bridging and bridging oxygen would be formed in the sample glasses.

We performed radiofrequency catheter ablation in five patients associated with Ebstein's anomaly to cure their refractory tachyarrhythmias. The presenting arrhythmias were four cases of orthodromic circus movement tachycardia using accessory pathways as a requisite limb, including one case of a Mahaim fiber and one of atrial flutter of common variety. All accessory pathways, including the Mahaim fiber, were ablated by RF energy delivered through the catheter placed at the AV annulus rather than the displaced anatomical AV groove. Interestingly, the antegrade or retrograde conduction interval over these accessory pathways was relatively longer than that of usual accessory pathways, and the accessory pathway potential was fractionated in some cases. The location of the atrioventricular node was displaced from the usual position to the postero-inferior area of Koch's triangle in one case. The configuration of the flutter wave was larger than usual in height as well as in width. All tachyarrhythmias were cured by RF catheter ablation. In the case of RF catheter ablation for patients with Ebstein's anomaly, close attention is indispensable in order to accomplish it safely and successfully, because of the anatomical and functional differences peculiar to Ebstein's anomaly.

Six carotenoids, including carotenoid glucoside fatty acid esters, have previously been identified in Rhodococcus rhodochrous RNMS1. From its colour mutant, two carotenoids with apparently very low polarities on reversed phase HPLC were found to be carotenoid glucoside mycolic acid esters. From spectroscopic and chemical evidence, their structures were determined as 1′-[(6- O -mycoloyl-β- d -glucopyranosyl)oxy]-1′,2′-dihydro-β,ψ-caroten-4-one and 1′-[(6- O -mycoloyl-β- d -glucopyranosyl)oxy]-1′,2′-dihydro-β,ψ-carotene. Their mycolic acid residues were similar to those of the cellular mycolic acids. In all strains of R. rhodochrous tested, these carotenoid derivatives were found. Such carotenoid derivatives have never been reported in other organisms.

Objectives. The aim of this study was to examine the effect of ischemic preconditioning on the manner of ventricular repolarization by assessing the change in QT dispersion during coronary angioplasty. Background. QT interval dispersion regional variations in ventricular repolarization and cardiac electrical instability. Previous studies have suggested that increased QT dispersion is associated with an increased incidence of malignant ventricular arrhythmias, whereas brief episodes of myocardial ischemia can render the heart more resistant to subsequent ischemic episodes, a phenomenon called ischemic preconditioning. Methods. To assess the effects of ischemic preconditioning on myocardial repolarization by examining the change in QT dispersion during coronary angioplasty, we studied 47 consecutive patients (39 men and 8 women; mean age 57 ± 16 years). QT dispersion was measured after each balloon inflation during coronary angioplasty. Statistical analysis was performed by using repeated measurement of analysis of variance. Results. There were significant differences in QT dispersion as the number of balloon inflations increased (mean ± SD 52 ± 14, 42 ± 11, 36 ± 9, 31 ± 10 and 29 ± 11 ms, respectively [p < 0.01], for the first, second, third, fourth and fifth balloon inflations). The magnitude of decrease in QT dispersion was significant in the first and second balloon inflations, then became insignificant with later inflations. Conclusions. These data indicate that the gradual decrease in OT dispersion provoked by coronary artery occlusion and reperfusion during coronary angioplasty may be associated with electrophysiologic effects of ischemic preconditioning on myocardium in the human heart.