Search

Background Rapid reduction of heart rate (HR) is the most evident physiological response of vagal nerve stimulation (VNS). Since HR reduction is the most potent factor to decrease myocardial oxygen consumption rate (MVO2), the appropriate VNS can exert cardio-protective effects. It is also known that VNS reduces inflammation, oxidative stress, and sympathetic overload. In addition, the VNS during ischemia-reperfusion is known to attenuate myocardial damage by studies in various animal species. Despite the presence of preclinical evidence of VNS benefits, the lack of the device has limited the translation of this technology to clinical practice. We have recently developed an intravenous VNS catheter (JOHAKU, Neuroceuticals Inc.) that can stimulate the right vagal nerve via superior vena cava (SVC) (Figure 1) on temporary basis. Purpose We aimed to confirm the feasibility of JOHAKU as a device to modulate heart rate and MVO2 rapidly by a canine experiment. Methods In eight beagle dogs, JOHAKU was inserted from the right femoral vein and placed at the SVC level. The stimulation intensity was adjusted to 10–20 V (20 Hz). We simultaneously recorded electrocardiogram and intraarterial blood pressure (BP). In three of eight dogs, we measured the left anterior descending coronary artery flow and oxygen saturations of arterial and coronary sinus blood to calculate MVO2. We compared HR, BP, and MVO2 during JOHAKU stimulation to ones at baseline. Results As shown in Figure 2, JOHAKU attenuated HR immediately after stimulation. Compared with baseline, JOHAKU significantly reduced HR (baseline: 135±13 vs. 5 min on stimulation: 107±13 bpm, p Conclusion JOHAKU rapidly attenuated cardiac metabolism burden via the rapid HR reduction. The controllability of HR by JOHAKU without affecting BP enables us to apply the VNS even for patients with hemodynamic instability, such as heart failure and acute myocardial infarction. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Agency for Medical and Research Development

Pendulum thrust stands are used to measure the thrust of electric propulsion systems for spacecraft. A thruster is mounted on a pendulum and operated, and the pendulum displacement due to thrust is measured. In this type of measurement, the pendulum is also affected by nonlinear tensions due to wiring and piping that deteriorate the accuracy of the measurement. This influence cannot be ignored in high power electric propulsion systems because complicated piping and thick wirings are required. Therefore, to reduce the influence of tension due to wires and tubes, we developed an inverted pendulum-type thrust stand with pipes and wirings as springs. In this paper, we first derive the design guidelines for spring-shaped wires; the necessary conditions for sensitivity, responsivity, spring shape, and electric wire were formulated. Next, a thrust stand was designed and fabricated based on these guidelines, and the performance of the stand was evaluated through calibration and thrust measurements using a 1 kW-class magneto-plasma-dynamics thruster. The sensitivity of the thrust stand was 17 mN/V, the normalized standard deviation of the variation of the measured values owing to the structure of the thrust stand was 1.8 × 10−3, and the thermal drift during the long-time operation was ∼4.5 × 10−3 mN/s.

The data of simultaneous observation of the energetic electron flux by ARASE satellite and aurora by ground-based all-sky imager in Murmansk region (Russia) have been analyzed for the time interval 00:00-01:00 UT on March 31, 2017. The energy spectra of middle-energy (7-90 keV) electrons observed by MEPe detectors in and near the loss cone have been used for simulation of the auroral emissions in the atmosphere. The temporal evolution of the simulated emission intensity has been compared with the observed emission in the magnetic field-aligned footprint point for the satellite. It was found that the projection along magnetic field has been distorted by the developing disturbance.

Background It has been reported that discordance between fractional flow reserve (FFR) and Instantaneous Wave-Free Ratio (iFR) could occur in up to 20% of cases. However, there are no reports regarding discordance between FFR and iFR in patients with severe aortic valve stenosis (AS). Purpose We aimed to investigate the discordance between FFR and iFR in patients with severe AS. Methods Severe AS was defined as an aortic-valve area of ≤1.0 cm2, a mean aortic-valve gradient of 40mmHg or more, or a peak aortic-jet velocity of 4.0 m/s or more. Intermediate coronary artery stenosis was defined as 30% to 70% stenosis (visual estimation). FFR and iFR were calculated in 4 quadrants based on values of FFR ≤0.8 and iFR ≤0.89 (positive discordance; low FFR and high iFR, negative discordance; high FFR and low iFR). Results We examined consecutive 140 patients (164 intermediate coronary artery stenosis vessels). Mean FFR and iFR ± standard deviation was 0.82±0.09 and 0.82±0.14, respectively. The discordance was observed in 48 vessels (29.3%). In the discordant group, most of cases were negative discordance (45 cases, 93.6%). Binary logistic regression analysis showed that left anterior descending artery (Hazard Ratio 3.80; 1.55 to 9.31, p=0.0036) was independently associated with negative discordance. Conclusions In patients with severe AS, the discordance between FFR and iFR could be observed in 29.3% of the vessels, mostly negative discordance. The left anterior descending artery is an independent predictor for negative discordance. Funding Acknowledgement Type of funding source: None

Background In recent years it has been attempted to use a distal radial artery (DRA) as a puncture site for cardiac catheterization and intervention. A patency of radial artery is important in hemodialysis patients because the radial artery is source as an arteriovenous shunt. However, the incidence of radial artery occlusion (RAO) is not known after DRA puncture. Purpose To compare RAO rates after DRA puncture between dialysis and non-dialysis patients. Method This was retrospective, observational and single center study. All consecutive 1,533 patients undergoing DRA puncture were analyzed. The primary endpoint is RAO rates. The secondary endpoint is composite bleeding adverse event rates. These endpoints were evaluated by a vascular echocardiography several hours or the next day after the procedure. Result Among 1,533 patients, 26 were dialysis patients and 1,504 were non-dialysis patients. 1,386 people (90.5%) succeeded in puncture. Radial artery occlusion occurred in 7 patients (0.4%), all of whom were non-dialysis patients. There was no significant difference of RAO rate in dialysis patients and non-dialysis patients. Conclusion When performing DRA puncture, the probability of radial artery occlusion is not higher in dialysis patients than non-dialysis patients. The DRA puncture may be one of the option as puncture site even in dialysis patients.

In this paper, the mechanical performance of asphalt mixtures was examined in cyclic torsional shear test, in which the relationship between the averaged shear strain, γav, and the number of cyclic loading, N, was obtained by using a short, about 25mm height, specimen. In these tests, the effects of some influencing factors such as the type of asphalt mixture, the thickness of specimen and the temperature were examined. In each test, four indices; i.e., the slope of plastic flow line, the slope of stripping line, the number of load applications at the inflection point for stripping and the averaged shear strain at the inflection point for stripping, were defined for the relationship between γav and N. As a result of this study, we clarified that various performances such as rutting resistance, fatigue failure resistance and the stripping resistance of asphalt mixture can be appropriately evaluated by using the cyclic torsional shear test.

Background Systemic juvenile idiopathic arthritis (SJIA) is a distinct form of juvenile idiopathic arthritis (JIA), accounting for approximately 4% to 17% of JIA1. In Japan, a higher frequency of SJIA, 41.7% of JIA2 has been reported compared to Europe and United States. Tocilizumab (TCZ) is the only approved biologic for SJIA treatment in Japan. However, some patients (pts) demonstrate persistently high disease activity and/or drug intolerabiliy. Therefore, new treatment options are required. Here, we evaluated the efficacy and safety of canakinumab (CAN), a human anti-interleukin-1s monoclonal antibody, in Japanese SJIA pts. Objectives To report the results of a 28 week (Wk) interim whole analysis of Phase III data (NCT02396212) of CAN, and the subgroup analysis of pts with or without prior use of TCZ. Methods Patients (age ≥2- Results The trial enrolled 19 pts who had insufficient response to prior treatment; the majority (15/19, 78.9%) had received TCZ (table 1). Of the 19 pts, 3 discontinued CAN due to lack of efficacy or adverse events (AE) by Wk28 and 16 completed the assessment of Wk28. All pts (19/19) achieved aACR 30/50/70 at Wk8 (figure 1). Overall, 73.7% (14/19) pts achieved corticosteroid tapering at Wk28 and 2 pts (10.5%) achieved ”steroid free”. Of 15 pts with prior use of TCZ, 12 pts (80.0%) achieved aACR 100 at Wk8 and 11 pts (73.7%) achieved corticosteroid tapering (26.3%, 5/19). Serious AE (SAE) was seen in 41.1% (8/19) pts, and the most frequent SAE was JIA (flare or worsening of SJIA, 21.1%, 4/19). One macrophage activation syndrome (MAS) but no death was reported. Conclusions CAN 4 mg/kg q4w s.c. provided improvement in disease activity and a redution of oral steroid dose in Japanese SJIA pts, including those who were not well-controlled with TCZ. No new safety concerns were reported. References [1] Ravelli A, Martini. Lancet2007; 369(9563):767–78. [2] Takei S, et al. Annual Report on children with chronic refractory diseases from the Japanese Ministry of Health, Labor and Welfare2008;102–13. Disclosure of Interest None declared

mRNAs for proteins required in elongated spermatids are considered to be transcribed at an early stage and stored in cytoplasm, presumably in chromatoid body (CB), one type of nuage component (a unique structure that appears and disappears during spermatogenesis), because transcription of genes does not occur at late stages. In elongated spermatids, a large amount of tubulin molecules is required to form microtubules of manchette and flagellum. To investigate the possible role of CB in translation of tubulin mRNA, we performed immunofluorescence and immunoelectron microscopic localization studies of α- and β-tubulin in rat spermatogenic cells. β-tubulin was detected in CB, but α-tubulin was not. Other nuage components present in pachytene spermatocytes (ISPG, IMC, SB) were negative for both α- and β-tubulin. Our findings suggest that: (i) β-tubulin in round spermatids is translated within the CB, whereas α-tubulin is not; (ii) αβ-heterodimers are formed outside CB and incorporated into microtubules of manchette and flagellum.

OBJECTIVE Prospective trials specifically designed for elderly patients with advanced non-small-cell lung cancer demonstrating the benefit of platinum-based therapies are still lacking. This trial was designed to clarify whether the addition of cisplatin to monotherapy could improve survival for elderly patients. METHODS Elderly patients (age ≥70 years, ECOG performance Status 0-1) with advanced non-small-cell lung cancer were randomized to receive docetaxel 20 mg/m(2) plus cisplatin 25 mg/m(2) on Day 1, 8 and 15 (docetaxel plus cisplatin) or docetaxel 25 mg/m(2) on the same schedule (docetaxel). Both regimens were repeated every 4 weeks until disease progression. RESULTS One hundred and twenty-six patients were enrolled. Sixty-three were randomly assigned docetaxel plus cisplatin and 63 docetaxel monotherapy. Median age was 76 years (range 70-88). The second planned interim analysis was performed on 112 assessable patients (docetaxel/docetaxel plus cisplatin: 56/56). Although the formal criterion for stopping the trial was not met, the Data and Safety Monitoring Committee recommended study termination on ethical grounds based on the interaction (two-sided P = 0.077, hazard ratios for ≤74/≥75: 0.23/0.72) between age and subgroup and treatment arm, which suggested that docetaxel may not represent an adequate control arm regimen for the age subgroup of 70-74 years. CONCLUSIONS The interpretation of study results is limited due to early stopping. Further study is needed to confirm survival benefit of platinum-based chemotherapy for elderly non-small-cell lung cancer [UMIN-CTR (www.umin.ac.jp/ctr/) ID: C000000146].

Systemic juvenile idiopathic arthritis (s-JIA) is a rare inflammatory disease classified as a subtype of chronic childhood arthritis, manifested by spiking fever, erythematous skin rash, pericarditis and hepatosplenomegaly. The genetic background underlying s-JIA remains poorly defined. To detect copy number variations, we performed single nucleotide polymorphism (SNP) array analysis in 50 patients with s-JIA. We found a 13-kb intragenic deletion of CASP10 in one patient. RT-PCR of the mRNA extracted from the patient's lymphoblastoid cells revealed that CASP10 mRNA was truncated. Sequencing the mRNA revealed that this deletion resulted in a frame shift with an early stop codon. CASP10 is known as a causative gene for autoimmune lymphoproliferative syndrome (ALPS) type IIa, another childhood syndrome of lymphadenopathy and splenomegaly associated with autoimmune haemolytic anaemia and thrombocytopenia. TCR αβ(+) CD4/CD8 double-negative T cells in the peripheral blood as a diagnostic marker of ALPS were not high in this patient and lymphocyte apoptosis induced by anti-Fas antibody was normal, denying ALPS in the patient. The father and a sister of the patient showing no symptoms of ALPS or s-JIA, also had the same deletion. Furthermore, we found no other mutations of CASP10 in the other 49 s-JIA patients. These data suggest that the pathogenic significance of CASP10 mutations should be carefully evaluated in s-JIA or even ALPS type IIa in further studies.

A survey of existing data suggests that trophoblast cells produce factors involved in extracellular matrix degradation. In this study, we correlated the expression of cathepsins D and B in the murine ectoplacental cone with the ultrastructural progress of decidual invasion by trophoblast cells. Both proteases were immunolocalized at implantation sites in lysosome-endosome-like compartments of trophoblast giant cells. Cathepsin D, but not cathepsin B, was also detected ultrastructurally in extracellular compartments surrounded by processes of the invading trophoblast containing extracellular matrix components and endometrial cell debris. The expression of cathepsins D and B by trophoblast cells was confirmed by RT-PCR in ectoplacental cones isolated from implantation chambers at gestation day 7.5. Our data addressed a positive relationship between the expression and presence of cathepsin D at the extracellular compartment of the maternal-fetal interface and the invasiveness of the trophoblast during the postimplantation period, suggesting a participation of invading trophoblast cells in the cathepsin D release. Such findings indicate that mouse trophoblast cells might exhibit a proteolytic ability to partake in the decidual invasion process at the maternal-fetal interface.

著者人数: 42名, Accepted: 2007-08-24, 資料番号: SA1000710000

We report on a Suzaku observation of the nearby Seyfert 2 galaxy NGC 4388. The overall spectrum is well described by the combination of strongly absorbed power-law plus thin thermal plasma emission, as well as previous observations. Thanks to well-calibrated instruments and a low background level, Suzaku measured the broad-band X-ray spectra more precisely than ever, and enabled us to probe the physical structure of the nuclear region. In addition, a time variability having a factor of 1.5 with a half-day time scale was found up to above 10 keV. The center energy and the Kˇ/K ratio of the narrow Fe-K line, together with less time variability, indicate that the fluorescent material is far from the black hole. A spectral hump around the 30–40 keV band, together with a Compton shoulder of the Fe-K line, requires a significant contribution of the reflection component. This is also consistent with a smaller amplitude of time variability in a higher energy band. A large contribution of the reflection component was not observed by the CGRO/OSSE and BeppoSAX, suggesting that NGC 4388 had been in a higher flux state, and that Suzaku observed its light echo. A He-like Fe-K absorption line was also detected, indicating the existence of highly ionized plasma.

Electro-conjugate fluid (hereafter abbreviated as ECF) is a kind of dielectric fluid that produces a powerful jet flow (ECF jet) between rod-type electrodes in an applied non-uniform static electric field. By using the ECF jet, a new type of micromotor with a simple structure and light weight can be realized. Until now, some types of ECF micromotors have been developed with a 3 mm inner diameter. In this study, a micromotor is fabricated with a 2 mm inner diameter in order to improve the output power density, using the ECF jet. The micromotor was first designed and fabricated; then, the performance of the motor was measured. The experimental results confirm that the micromotor developed here has a higher power density than the micromotors previously developed with 3 mm inner diameter.

Background The prognosis of ventricular tachycardia (VT) in children with overt heart disease is generally good, so the aim of this study was to review the prognosis and necessity of treatment of VT that detected by school-based heart disease screening. Methods and Results Of the 48 cases of pediatric VT that have been followed for 2-30 years, 17% were diagnosed at the first school-based screening test (12-lead ECG at rest) and the remainder who had premature ventricular contractions (PVC) on the resting 12-lead ECG required Holter ECG test and exercise stress ECG test to detect VT. In 90% of cases, VT in healthy children is idiopathic non-sustained VT and more than half of the present cases showed natural disappearance of the VT during follow up. In particular, cases of monomorphic PVC or maximum PVC runs less than 5 had a good prognosis. The cases of polymorphic VT and VT with heart disease continued for the long term. Conclusion Treatment is unnecessary for monomorphic VT with the maximum number of salvos less than 5. The necessity for treatment depends on the symptoms and profile of the VT. The prognosis for polymorphic VT and underlying heart disease is not good and may require implantable cardioverter defibrillator. (Circ J 2005; 69: 273 - 276)

ejd.2013.1953 Auteur(s) : Hiroyuki Fujita1 fuji_fuji_fuji_0101@yahoo.co.jp, Tomoya Watanabe1, Rika Okada1, Yuu Nozaki1, Motoko Ayabe1, Tomoyuki Imagawa2, Shunpei Yokota2, Michiko Aihara1 1 Department of Environmental Immuno-Dermatology, 2 Department of Pediatrics, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa, Yokohama, 236-0004, Japan Fixed drug eruption (FDE) is a cutaneous adverse drug reaction characterized by recurrence at the same skin or mucous membrane sites [...]

A study is reported of the temperature dependence of the nuclear spin-lattice relaxation rate 1/ T 1 of 93 Nb in a superconducting NbN with cubic B1 structure and with T C of about 16 K. Powdered samples of NbN mainly prepared by self-propagating high-temperature synthesis (SHS) have been used. The recovery of the nuclear magnetization from saturation did not show a simple exponential one and is interpreted by a multi-exponential recovery appropriate in this case of spin 9/2. Prominent features of the experimental results are as follows. (1) The relaxation rate 1/ T 1 of 93 Nb follows the Korringa relation above T C . (2) The rate has a bump just below T C , which is considered to be a so-called coherence peak. (3) The data at low temperature can be interpreted by an activation-type temperature dependence, which allows estimating the value of 2 Δ / k B T C to be 3.5. (4) The NMR shift of 93 Nb is decreased below T C . These experimental results seem to indicate that the superconducting mechanism in NbN is due to the conventional BCS mechanism.

The fatty acid synthase (FASN) and stearoyl-CoA desaturase (delta-9-desaturase) (SCD) genes affect fatty acid composition. This study evaluated the contributions of polymorphisms of these genes on fatty acid composition in muscle in two different populations: 1189 and 1058 Japanese Black cattle from the Miyagi and the Yamagata populations respectively. We sampled intramuscular fat from the longissimus thoracis muscle in the Miyagi population and from the trapezius muscle in the Yamagata population. The collective contributions of FASN and SCD polymorphisms to total additive genetic variance for oleic acid were 13.46% in the Miyagi population and 16.29% in the Yamagata population and to phenotypic variance were 5.45% and 6.54% respectively. Although the individual effects of FASN and SCD polymorphisms on fatty acid composition were small, overall gene substitution may effectively improve fatty acid composition. In addition, we found that gene polymorphism contributions of fatty acids varied by population even in the same breed.

To understand the molecular mechanisms underlying the terrestrial adaptation, as well as adaptation to different salinities, of the euryhaline and amphibious mudskipper ( Periophthalmus modestus), we have looked for the skin mRNAs that change during varying environmental conditions. Using differential mRNA display polymerase chain reaction, we compared skin mRNAs in mudskipper transferred from isotonic 30% seawater to fresh water or to seawater for 1 day and 7 days, as well as those kept out of water for 1 day. At the end of these periods, poly(A(+))RNA was prepared from the Cl(-)-secreting pectoral skins and also from the outer opercular skins where ion transport is negligible, and analyzed by differential display. We identified four cDNA products expressed differently under various environments as homologues of known genes. A further 34 cDNAs were expressed differentially, but they have no significant homology to identified sequences in GenBank. Northern blots demonstrate that mRNA levels of the actin-binding protein and the platelet-activating factor acetylhydrolase increased in the pectoral skins during seawater acclimation. The mRNA of the 90 kDa heat shock protein was down-regulated in water-deprived and freshwater fish, whose plasma cortisol levels were high. The aldolase mRNA was induced in both skins after desiccation. These four genes may be involved in the environmental adaptations.

We report a case of mitochondrial cardiomyopathy in a Japanese boy who presented with severe cardiac heart failure and died 6 days after admission. The onset of mitochondrial cardiomyopathy often occurs very early in childhood and has a rapid downward course.