Endourological Evaluation and Management of Leukoplakia of the Renal Pelvis

Since August 1989, we have seen 4 patients with leukoplakia of the renal pelvis associated with a longstanding renal stone. In 2 of them, excretory or retrograde pyelography revealed multiple filling defects in the left renal pelvis as well as a renal stone, although urine cytological examination was negative. One of the other 2 patients underwent extracorporeal shock wave lithotripsy (ESWL) for the renal stone, but this was not followed by the passage of stone fragments. The renal stone in the remaining patient was associated with staghorn calculi. For stone extraction as well as endoscopic evaluation of the intrapelvic lesion, percutaneous nephroscopy was performed. A small to large amount of tissue-like white debris in sheets characteristic of leukoplakia was found in the renal pelvis with stones embedded in it and was removed directly by forceps or suction and then by irrigating with saline. We propose that 1) the endourological approach should be recommended for patients with renal pelvic lesions associated with longstanding renal stones or for patients who show difficulty in passing stone fragments after ESWL and 2) this entity of leukoplakia should be kept in mind for the differential diagnosis of renal pelvic lesions associated with renal stones

Improvement of acquisition and analysis methods in multi-electrode array experiments with iPS cell-derived cardiomyocytes

AbstractIntroductionMulti-electrode array (MEA) systems and human induced pluripotent stem (iPS) cell-derived cardiomyocytes are frequently used to characterize the electrophysiological effects of drug candidates for the prediction of QT prolongation and proarrhythmic potential. However, the optimal experimental conditions for obtaining reliable experimental data, such as high-pass filter (HPF) frequency and cell plating density, remain to be determined.MethodsExtracellular field potentials (FPs) were recorded from iPS cell-derived cardiomyocyte sheets by using the MED64 and MEA2100 multi-electrode array systems. Effects of HPF frequency (0.1 or 1Hz) on FP duration (FPD) were assessed in the presence and absence of moxifloxacin, terfenadine, and aspirin. The influence of cell density on FP characteristics recorded through a 0.1-Hz HPF was examined. The relationship between FP and action potential (AP) was elucidated by simultaneous recording of FP and AP using a membrane potential dye.ResultsMany of the FP waveforms recorded through a 1-Hz HPF were markedly deformed and appeared differentiated compared with those recorded through a 0.1-Hz HPF. The concentration–response curves for FPD in the presence of terfenadine reached a steady state at concentrations of 0.1 and 0.3μM when a 0.1-Hz HPF was used. In contrast, FPD decreased at a concentration of 0.3μM with a characteristic bell-shaped concentration–response curve when a 1-Hz HPF was used. The amplitude of the first and second peaks in the FP waveform increased with increasing cell plating density. The second peak of the FP waveform roughly coincided with AP signal at 50% repolarization, and the negative deflection at the second peak of the FP waveform in the presence of E-4031 corresponded to early afterdepolarization and triggered activity.DiscussionFP can be used to assess the QT prolongation and proarrhythmic potential of drug candidates; however, experimental conditions such as HPF frequency are important for obtaining reliable data

空間群P1^^ーにおける楕円体の最密充填

空間群P1^^ー(三斜晶系)に属する単位格子内に1個の楕円体をもった場合の最密充填構造を、マイクロソフト社製ExcelとVBAを使って調べた. 最大充填率74.05%を与える16種の楕円体が存在する. これらの楕円体は異なった接触環境にあり、いずれも12個の楕円体と接触している. 接触環境は格子軸の変換によって特定の接触環境に変えることができる. 接触環境を層の積み重ねからみると、積み重ね方に2つのタイプがある. 第1のタイプは層内において6個の楕円体と接触した楕円体が上の層と下の層とでそれぞれ3個の楕円体と接触し、第2のタイプは層内で4個の楕円体と接触した楕円体が上の層と下の層とでそれぞれ4個の楕円体と接触している.The closest packing structure when having 1 ellipsoid in the unit cell which belongs to space group P1^^-(Triclinic system), was checked using Excel made by Microsoft Corporation and VBA. 16 kinds of ellipsoid to which the closest packing rate 74.05% is given exist. These ellipsoids contact with 12 ellipsoids both in the different contact environments. It\u27s possible to change the contact environment to the specific contact environment by a change in an axis of unit cell. When we look at the contact environments from stacking of layers, there are 2 types in stacking of layers. In the 1st type, the ellipsoid contacts with 6 ellipsoids in the layer and with 3 ellipsoids in an upper layer and a lower layer respectively. In the second type, the ellipsoid contacts with 4 ellipsoids in the layer and with 4 ellipsoids in an upper layer and a lower layer respectively

A Shock-Induced Pair of Superbubbles in the High-Redshift Powerful Radio Galaxy MRC 0406-244

We present new optical spectroscopy of the high-redshift powerful radio galaxy MRC 0406$-$244 at redshift of 2.429. We find that the two extensions toward NW and SE probed in the rest-frame ultraviolet image are heated mainly by the nonthermal continuum of the active galactic nucleus. However, each extension shows a shell-like morphology, suggesting that they are a pair of superbubbles induced by the superwind activity rather than by the interaction between the radio jet and the ambient gas clouds. If this is the case, the intense starburst responsible for the formation of superbubbles could occur $\sim 1 \times 10^9$ yr ago. On the other hand, the age of the radio jets may be of the order of $\sim 10^6$ yr, being much shorter than the starburst age. Therefore, the two events, i.e., the starburst and the radio-jet activities, are independent phenomena. However, their directions of the expanding motions could be governed by the rotational motion of the gaseous component in the host galaxy. This idea appears to explain the alignment effect of MRC 0406$-$244.Comment: 4 pages (emulateapj.sty), Fig. 1 (jpeg) + Fig.2 (eps). Accepted for publications in ApJ (Letters

Decomposition of the Superwind in M82

We present new optical images ($B$, $V$, and H$\alpha$) of the archetypical starburst/superwind galaxy M82 obtained with the 8.2 m Subaru Telescope to reveal new detailed structures of the superwind-driven nebula and the high-latitude dark lanes. The emission-line nebula is decomposed into (1) a ridge-dominated component comprising numerous filament/loop sub-structures whose overall morphology appears as a pair of narrow cylinders, and (2) a diffuse component extended over much wider opening angle from the nucleus. We suggest that these two components have different origins. The ridge-dominated component appears as a pair of cylinders rather than a pair of cones. Since this morphological property is similar to that of hot plasma probed by soft X-ray, this component seems to surround the hot plasma. On the other hand, the diffuse component may arise from dust grains which scatter stellar light from the galaxy. Since inner region of this component is seen over the prominent ^^ ^^ X"-shaped dark lanes streaming out from the nuclear region and they can be reproduced as a conical distribution of dust grains, there seems to be a dusty cold outflow as well as the hot one probed by soft X-ray and shock-excited optical emission lines. If this is the case, the presence of such high-latitude dust grains implies that neutral gaseous matter is also blown out during the course of the superwind activity.Comment: 12 pages, 6 figures. Accepted for publication in PAS

Palmitoylated ras proteins traffic through recycling endosomes to the plasma membrane during exocytosis

Ras proteins regulate cell growth, death, and differentiation, and it is well established that this functional versatility is accomplished through their different subcellular localizations. Palmitoylated H- and N-Ras are believed to localize at the perinuclear Golgi and plasma membrane (PM). Notably, however, recycling endosomes (REs) also localize to a perinuclear region, which is often indistinguishable from the Golgi. In this study, we show that active palmitoylated Ras proteins mainly localize intracellularly at REs and that REs act as a way station along the post-Golgi exocytic pathway to the PM. H-Ras requires two palmitoyl groups for RE targeting. The lack of either or both palmitoyl groups leads to the mislocalization of the mutant proteins to the endoplasmic reticulum, Golgi apparatus, or the PM. Therefore, we demonstrate that palmitoylation directs Ras proteins to the correct intracellular organelles for trafficking and activity. © 2010 Misaki et al

Severe Aortic Stenosis in Dialysis Patients

Background: Characteristics and prognosis of hemodialysis patients with severe aortic stenosis have not yet been well defined. Methods and Results: The CURRENT AS (contemporary outcomes after surgery and medical treatment in patients with severe aortic stenosis) registry, a Japanese multicenter registry, enrolled 3815 consecutive patients with severe aortic stenosis. There were 405 hemodialysis patients (initial aortic valve replacement [AVR] group: N=135 [33.3%], and conservative group: N=270) and 3410 nonhemodialysis patients (initial AVR group: N=1062 [31.1%], and conservative group: N=2348). The median follow‐up duration after the index echocardiography was 1361 days, with 90% follow‐up rate at 2 years. The cumulative 5‐year incidence of all‐cause death was significantly higher in hemodialysis patients than in nonhemodialysis patients in both the entire cohort (71% versus 40%, P<0.001) and in the initial AVR group (63.2% versus 17.9%, P<0.001). Among hemodialysis patients, the initial AVR group as compared with the conservative group was associated with significantly lower cumulative 5‐year incidences of all‐cause death (60.6% versus 75.5%, P<0.001) and sudden death (10.2% versus 31.7%, P<0.001). Nevertheless, the rate of aortic valve procedure–related death, which predominantly occurred within 6 months of the AVR procedure, was markedly higher in the hemodialysis patients than in the nonhemodialysis patients (21.2% and 2.3%, P<0.001). Conclusions: Among hemodialysis patients with severe aortic stenosis, the initial AVR strategy as compared with the conservative strategy was associated with significantly lower long‐term mortality risk, particularly the risk for sudden death, although the effect size for the survival benefit of the initial AVR strategy was smaller than that in the nonhemodialysis patients

Decline in Left Ventricular Ejection Fraction during Follow-up in Patients with Severe Aortic Stenosis

Objectives: The aim of this study was to investigate the prognostic impact of the decline in left ventricular ejection fraction (LVEF) at 1-year follow-up in patients with severe aortic stenosis (AS) managed conservatively. Background: No previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS. Methods: Among 3, 815 patients with severe AS enrolled in the multicenter CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry in Japan, 839 conservatively managed patients who underwent echocardiography at 1-year follow-up were analyzed. The primary outcome measure was a composite of AS-related deaths and hospitalization for heart failure. Results: There were 91 patients (10.8%) with >10% declines in LVEF and 748 patients (89.2%) without declines. Left ventricular dimensions and the prevalence of valve regurgitation and atrial fibrillation or flutter significantly increased in the group with declines in LVEF. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the group with declines in LVEF than in the group with no decline (39.5% vs. 26.5%; p 10% declines in LVEF at 1 year after diagnosis had worse AS-related clinical outcomes than those without declines in LVEF under conservative management. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140

Initial Surgical Versus Conservative Strategies in Patients With Asymptomatic Severe Aortic Stenosis

AbstractBackgroundCurrent guidelines generally recommend watchful waiting until symptoms emerge for aortic valve replacement (AVR) in asymptomatic patients with severe aortic stenosis (AS).ObjectivesThe study sought to compare the long-term outcomes of initial AVR versus conservative strategies following the diagnosis of asymptomatic severe AS.MethodsWe used data from a large multicenter registry enrolling 3,815 consecutive patients with severe AS (peak aortic jet velocity >4.0 m/s, or mean aortic pressure gradient >40 mm Hg, or aortic valve area <1.0 cm2) between January 2003 and December 2011. Among 1,808 asymptomatic patients, the initial AVR and conservative strategies were chosen in 291 patients, and 1,517 patients, respectively. Median follow-up was 1,361 days with 90% follow-up rate at 2 years. The propensity score–matched cohort of 582 patients (n = 291 in each group) was developed as the main analysis set for the current report.ResultsBaseline characteristics of the propensity score–matched cohort were largely comparable, except for the slightly younger age and the greater AS severity in the initial AVR group. In the conservative group, AVR was performed in 41% of patients during follow-up. The cumulative 5-year incidences of all-cause death and heart failure hospitalization were significantly lower in the initial AVR group than in the conservative group (15.4% vs. 26.4%, p = 0.009; 3.8% vs. 19.9%, p < 0.001, respectively).ConclusionsThe long-term outcome of asymptomatic patients with severe AS was dismal when managed conservatively in this real-world analysis and might be substantially improved by an initial AVR strategy. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140

A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10−8). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10−4). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10−11). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS