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Background/Aims. Endoscopic sphincterotomy (EST) is often performed before fully covered self-expandable metal stent (FCSEMS) placement in order to prevent pancreatitis. However, it is not clear whether EST prevents pancreatitis or affects other adverse events (AEs). This study is conducted to evaluate the necessity of EST before FCSEMS placement for distal malignant biliary strictures due to a pancreatic head tumor. Methods. This study included 68 patients who underwent FCSEMS placement for distal malignant biliary stricture due to a pancreatic head tumor. Treatment outcomes and AEs were retrospectively compared between 32 patients with EST before FCSEMS placement (EST group) and 36 patients without EST (non-EST group). Results. The success rates of drainage for the EST and non-EST groups were 100% and 97.2%, respectively (P=0.95). The incidence of pancreatitis in the EST and non-EST groups was 3.1% and 0%, respectively (P=0.95). The incidence of hyperamylasemia in the EST and non-EST groups was 12.5% and 13.9%, respectively (P=0.85). The incidence of all AEs in the EST and non-EST groups was 15.6% (pancreatitis: 1, cholecystitis: 2, and stent migration: 2) and 13.9% (cholecystitis: 3, stent migration: 2), respectively (P=0.89). Conclusions. EST before FCSEMS placement for distal malignant biliary stricture due to a pancreatic head tumor does not affect the successful drainage and incidence of adverse events. The necessity of EST to prevent pancreatitis before FCSEMS placement was deemed low.

In situ cortisol excess was previously reported to promote cellular senescence, a cell response to stress, in cortisol-producing adenomas (CPA). The aim of this study was to explore senescence pathways in aldosterone-producing cells and related disorders, and the influence of aldosterone overproduction on in situ senescence. We analyzed 30 surgical cases of aldosterone-producing adenoma (APA), 10 idiopathic hyperaldosteronism (IHA) and 19 normal adrenals (NA). CYP11B2 and senescence markers p16 and p21 were immunolocalized in all those cases above and results were correlated with histological/endocrinological findings. In the three cohorts examined, the zona glomerulosa (ZG) was significantly more senescent than other corticosteroid-producing cells. In addition, the ZG of adjacent non-pathological adrenal glands of APA and IHA had significantly higher p16 expression than adjacent non-pathological zona fasciculata (ZF), reticularis (ZR) and ZG of NA. In addition, laboratory findings of primary aldosteronism (PA) were significantly correlated with p21 status in KCNJ5-mutated tumors. Results of our present study firstly demonstrated that non-aldosterone-producing cells in the ZG were the most senescent compared to other cortical zones and aldosterone-producing cells in PA. Therefore, aldosterone production, whether physiological or pathological, could be maintained by suppression of cell senescence in human adrenal cortex.

During screening of protein-protein interactions, using human protein arrays carrying 19,676 recombinant glutathione s-transferase (GST)-fused human proteins, we identified the high-mobility protein group 20A (HMG20A) as a novel S100A6 binding partner. We confirmed the Ca2+-dependent interaction of HMG20A with S100A6 by the protein array method, biotinylated S100A6 overlay, and GST-pulldown assay in vitro and in transfected COS-7 cells. Co-immunoprecipitation of S100A6 with HMG20A from HeLa cells in a Ca2+-dependent manner revealed the physiological relevance of the S100A6/HMG20A interaction. In addition, HMG20A has the ability to interact with S100A1, S100A2, and S100B in a Ca2+-dependent manner, but not with S100A4, A11, A12, and calmodulin. S100A6 binding experiments using various HMG20A mutants revealed that Ca2+/S100A6 interacts with the C-terminal region (residues 311–342) of HMG20A with stoichiometric binding (HMG20A:S100A6 dimer = 1:1). This was confirmed by the fact that a GST-HMG20A mutant lacking the S100A6 binding region (residues 311–347, HMG20A-ΔC) failed to interact with endogenous S100A6 in transfected COS-7 cells, unlike wild-type HMG20A. Taken together, these results identify, for the first time, HMG20A as a target of Ca2+/S100 proteins, and may suggest a novel linkage between Ca2+/S100 protein signaling and HMG20A function, including in the regulation of neural differentiation.

Background/Aims. In early endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis due to choledocholithiasis, it is unclear that single-session stone removal can be safely performed. We examined the efficacy and safety of early single-session stone removal for mild-to-moderate acute cholangitis associated with choledocholithiasis. Methods. Among patients with mild-to-moderate acute cholangitis associated with choledocholithiasis who underwent early ERCP (n = 167), we retrospectively compared the removal group (patients who underwent single-session stone removal; n = 78) with the drainage group (patients who underwent biliary drainage alone; n = 89) and examined the effectiveness and safety of single-session stone removal by early ERCP. Results. The patients in the removal group had significantly fewer and smaller stones compared with those in the drainage group. The single-session complete stone removal rate was 85.9% in the removal group. The complication rate in early ERCP was 11.5% in the removal group and 10.1% in the drainage group, with no significant difference (P = 0.963). On comparing patients who underwent early endoscopic sphincterotomy (EST) with those who underwent elective EST after cholangitis had improved, the post-EST bleeding rates were 6.8% and 2.7%, respectively, with no significant difference (P = 0.600). The mean duration of hospitalization was 11.9 days for the removal group and 19.9 days for the drainage group, indicating a shorter stay for the removal group (P < 0.001). In multiple linear regression analysis, stone removal in early ERCP, number of stones, and C-reactive protein level were significant predictors of hospitalization period. Conclusions. Single-session stone removal for mild-to-moderate acute cholangitis can be safely performed. It is useful from the perspective of shorter hospital stay.

A series of study is presented to develop a prediction method for pipe wall thinning in power plants in order to improve the maintenance management for piping system. In the first report, experiments for flow-accelerated corrosion (FAC) of carbon steel specimens were conducted and basic data of FAC rate were obtained by setting temperature from 50 to 150 ℃ and pH from 7.0 to 9.8 as main parameters. As this second report, the experimental data of FAC rate were compared with the prediction method. Effective mass transfer coefficient correlation was proposed and implemented into the prediction method considering combining effect of local average and turbulent velocity in the near-wall region calculated by computational fluid dynamics (CFD) simulation code. Fairly good agreement was confirmed between experimental and predicted FAC rate profile, quantitatively. Continuously, prediction method was applied to actual power plant piping systems, and some elbow components were chosen for evaluation in detail. Comparison of measured and predicted FAC rate also showed good agreement with data mostly evaluated conservatively in sense of maintenance management. As a whole, presented FAC prediction method including effective mass transfer coefficient was confirmed to predict measured FAC rate data of power plant pipe component with fairly good accuracy and reasonable conservatism, at least for the subjected temperature and pH conditions.

In industrial fields, as the steam is commonly utilized for heat supply, drying process and so on, it is important to be aware of the steam flow rate in the view point of energy management. However, the steam utilized in the factory is usually wet steam condition. Though it is well known that the wetness affects the flowmeter reading, it is difficult to clarify the effects of the wetness in the steam flow quantitatively in actual plants and factories, and thus far, there has been no established method for estimating the error caused by the wetness of steam flow. In this paper, the difference of ultrasonic flowmeter reading due to wetness of the wet steam flow was clarified experimentally. Ultrasonic flowmeter reading in the wet steam flow was compared with Coriolis flow meter installed after heat exchanger in the steam apparatus. As a result, we clarified the flow rate difference of those two flowmeters was increased with increasing wetness, and the ultrasonic flowmeter reading was almost the same as the value of steam phase flow rate in the wet steam flow. We also proposed the correction method of the ultrasonic flowmeter reading by using density correction in the flow rate formula of the ultrasonic flowmeter. And finally, we clarified the uncertainty of the measured flowrates and their differences were less than 1.0%.

Platelet-activating factor (PAF) is a potent pro-inflammatory phospholipid mediator. In response to extracellular stimuli, PAF is rapidly biosynthesized by lyso-PAF acetyltransferase (lyso-PAFAT). Previously, we identified two types of lyso-PAFATs: lysophosphatidylcholine acyltransferase (LPCAT)1, mostly expressed in the lungs where it produces PAF and dipalmitoyl-phosphatidylcholine essential for respiration, and LPCAT2, which biosynthesizes PAF and phosphatidylcholine (PC) in the inflammatory cells. Under inflammatory conditions, LPCAT2, but not LPCAT1, is activated and upregulated to produce PAF. Thus, it is important to develop inhibitors specific for LPCAT2 in order to ameliorate PAF-related inflammatory diseases. Here, we report the first identification of LPCAT2-specific inhibitors, N-phenylmaleimide derivatives, selected from a 174,000-compound library using fluorescence-based high-throughput screening followed by the evaluation of the effects on LPCAT1 and LPCAT2 activities, cell viability, and cellular PAF production. Selected compounds competed with acetyl-CoA for the inhibition of LPCAT2 lyso-PAFAT activity and suppressed PAF biosynthesis in mouse peritoneal macrophages stimulated with a calcium ionophore. These compounds had low inhibitory effects on LPCAT1 activity, indicating that adverse effects on respiratory functions may be avoided. The identified compounds and their derivatives will contribute to the development of novel drugs for PAF-related diseases and facilitate the analysis of LPCAT2 functions in phospholipid metabolism in vivo.

We have studied a relationship between magnetic hysteresis and microstructures on high-tensile AISI 4340 steels after impact loading with a strain rate up to 2100 s−1 We find that coercivity, and minor-loop coefficient which is deduced from a power-law scaling between minor-loop parameters increase with strain rate, show a maximum at around a strain rate of 1400 s−1, followed by a decrease at a higher strain rate, associated with magnetic anisotropy with respect to impact direction. These observations are explained from the viewpoints of heat generation and heterogeneous microstructures characteristic to steels subjected to high strain rate deformation.

A series of study is presented to develop a prediction method for pipe wall thinning in power plants in order to improve the maintenance management for piping system. As the first report, experiments for flow-accelerated corrosion (FAC) of carbon steel specimens were conducted and basic data were obtained, focusing on relatively low temperature condition. FAC rate is seen to decrease by lowering temperature and the trend curve tends to remains to keep considerable level in lower temperature around 50 °C. Obtained data would mean that FAC susceptibility of pipeline in condensate demineralizer downstream and deaerator upstream in PWR plants is comparable. In terms of pH, a large drop in FAC rate is seen around pH 9.0 as in previous studies, and its ratio of pH 9.2 to pH 7.0 is approximately 1/10. This ratio fairly agrees with iron solubility in each pH condition at 150 °C while it is smaller in lower temperature condition, which may require additional effect related to pH and temperature to be considered to evaluate the FAC rate. The effect of iron contents on FAC rate is confirmed by referring to saturation solubility of iron. It is suggested that FAC may occur even when the iron concentration in the bulk water is in saturation level, which should be considered in the modelling process for FAC prediction.

Polyunsaturated fatty acids (PUFAs) in phospholipids affect the physical properties of membranes, but it is unclear which biological processes are influenced by their regulation. For example, the functions of membrane arachidonate that are independent of a precursor role for eicosanoid synthesis remain largely unknown. Here, we show that the lack of lysophosphatidylcholine acyltransferase 3 (LPCAT3) leads to drastic reductions in membrane arachidonate levels, and that LPCAT3-deficient mice are neonatally lethal due to an extensive triacylglycerol (TG) accumulation and dysfunction in enterocytes. We found that high levels of PUFAs in membranes enable TGs to locally cluster in high density, and that this clustering promotes efficient TG transfer. We propose a model of local arachidonate enrichment by LPCAT3 to generate a distinct pool of TG in membranes, which is required for normal directionality of TG transfer and lipoprotein assembly in the liver and enterocytes.

PURPOSE:Recent studies have shown that the risk of cerebro- and cardiovascular events (CVEs) is higher in patients with primary aldosteronism (PA) than in those with essential hypertension (EH), and that silent brain infarction (SBI) is a risk factor and predictor of CVEs. Here, we evaluated the relationship between findings from laser speckle flowgraphy (LSFG), a recently introduced non-invasive means of measuring mean blur rate (MBR), an important biomarker of ocular blood flow, and the occurrence of SBI in patients with PA. METHODS:87 PA patients without symptomatic cerebral events (mean 55.1 ± 11.2 years old, 48 male and 39 female) were enrolled in this study. We measured MBR in the optic nerve head (ONH) with LSFG and checked the occurrence of SBI with magnetic resonance imaging. We examined three MBR waveform variables: skew, blowout score (BOS) and blowout time (BOT). We also recorded clinical findings, including age, blood pressure, and plasma aldosterone concentration. RESULTS:PA patients with SBI (15 of 87 patients; 17%) were significantly older and had significantly lower BOT in the capillary area of the ONH than the patients without SBI (P = 0.02 and P = 0.03, respectively). Multiple logistic regression analysis revealed that age and BOT were independent factors for the presence of SBI in PA patients (OR, 1.15, 95% CI 1.01-1.38; P = .03 and OR, 0.73, 95% CI 0.45-0.99; P = .04, respectively). CONCLUSION:PA patients with SBI were older and had lower MBR BOT than those without SBI. Our analysis showed that age was a risk factor for SBI, and that BOT was a protective factor, in patients with PA. This suggests that BOT, a non-invasive and objective biomarker, may be a useful predictor of SBI and form part of future PA evaluations and clinical decision-making.