Search

Background Clinical hypertension is associated with renal inflammation and elevated circulating levels of proinflammatory cytokines. IL-1 receptor antagonist (IL-1Ra) is one of the most important anti-inflammatory cytokines and plays a crucial role in inflammation. Inhibition of IL-1 may contribute to modulation of the Angiotensin II (AngII)-induced hypertension response. This study aimed to elucidate the effects of IL-1Ra and anti-IL-1beta antibody (01BSUR) on AngII-induced hypertension and renal inflammation. Methods and results To determine the contribution of IL-1Ra to AngII-induced renal inflammation, male wild-type (WT) and IL-1Ra-deficient (IL-1Ra−/−) mice were infused with AngII (1000ng/kg/min) using subcutaneous osmotic pumps for 14 days. We checked blood pressure, histological change, and several mRNA expressions 14 days after infusion. Fourteen days after infusion, systolic blood pressure (197±5 vs 169±9 mmHg, p Conclusions Inhibition of interleukin-1 by both endogenous IL-1Ra and exogenous 01BSUR decreased AngII-induced hypertension and renal damage in mice, suggesting suppression of IL-1 may provide an additional strategy to protect against renal damage in hypertensive patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI

Background: Atherosclerosis is a chronic inflammatory disease responsible for most cases of heart disease and stroke in Western countries. The cytotoxic drug cyclophosphamide (CPA) can modulate immune functions, and it has therefore been used to treat patients with autoimmune diseases. Extension of survival of patients with severe atherosclerosis has been reported after CPA treatment, but the underlying mechanism is still poorly understood. Methods and results: We have investigated the effects of CPA in a murine model of atherosclerosis. Continuous oral administration of low-dose CPA (20 mg/kg/day) prevented atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice fed with a high fat diet. After 12 weeks, CPA treatment delayed progression of atherosclerosis in the mice (9.92% vs 3.32%, P

Background Left ventricular (LV) remodeling, through excessive inflammation, leads to heart failure. Exercise (Ex) training is associated with a risk reduction in heart failure through direct and indirect mechanisms by which Ex contributes an anti-inflammatory effect. During Ex, contracting muscle fibers release myokines, including interleukins (ILs), tumor necrosis factor α (TNF-α), follistatin-like protein 1 (FSTL-1), and fibroblast growth factor 21 (FGF-21), into the bloodstream. These myokines may have beneficial effects on other damaged organs, such as an infarcted myocardium, through anti-inflammatory effects. However, the exact mechanisms of the anti-inflammatory effects of voluntary Ex in myocardial infarction (MI) are poorly understood. Therefore, we investigated the effect of voluntary Ex on cardiac remodeling and inflammation, the relationship between cardiac remodeling and skeletal muscle (SKM) response, and circulating myokine levels in a mouse model of MI. Methods Twelve-week-old male C57BL/6J mice were used and divided into the following 4 groups: sham operation (Sham), MI, Sham+Ex, and MI+Ex. MI was induced by ligation of the left anterior descending coronary artery. Ex groups began voluntary wheel running for 4 weeks after the operation. An echocardiography was performed at baseline and 4 weeks after the operation. The mRNA levels in the LV infarcted area and SKM were measured with RT-PCR and western blot analysis. Plasma levels of myokines were also measured with immunoassays. Results Four weeks after MI induction, echocardiographic evaluation showed that the MI mice had a larger LV end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD) than the Sham mice. The MI mice also showed higher mRNA levels of TNF-α, IL-1β, IL-6, and IL-10 in the LV tissue when compared to the Sham mice. These changes were significantly ameliorated in the MI+Ex mice. Interestingly, in the MI+Ex mice, mRNA levels of IL-6, IL-1β, FSTL-1, and FGF-21 in the SKM were significantly higher than in the MI mice, while there were no significant differences in TNF-α and IL-10 levels in all groups. Similarly, protein expression levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, sirtuin-1, and mitochondrial transcriptional factor A of mitochondrial function markers in SKM were also significantly higher in the MI+Ex mice than in the MI mice. Furthermore, there were significant correlations between plasma levels of IL-1β, but not other myokines, and LVEDD, and LVESD. In addition, there was also a significant correlation between the SKM IL-1β level and LVESD in the Sham+Ex mice (all, P Conclusions Amelioration of cardiac remodeling and inflammation by voluntary Ex is associated with increased myokines, especially IL-1β, in a MI mouse model. These results suggest that increased myokine levels, through voluntary exercise, may play an important role in the prevention of cardiac remodeling after MI.

We have studied on the stress measurement by making use of salivary nitrate, which can be a candidate of stress markers, with ion-selective field-effect transistors (ISFETs). ISFETs are suitable for on-site single-drop analysis of salivary nitrate within 10 seconds. However, when ISFETs are used for salivary nitrate, ISFETs have a problem which is called the initial drift. The initial drift makes it difficult for determination of an accurate nitrate monitoring. Thus, the purpose of this study is to suppress an initial drift and to search for new easy polymer to possess more performance of sensor responses than conventional matrix membrane such as PVC. In this research, we investigated ISFETs using specific matrix membrane for example, KP-13, Pellethane® and P7281-PU. The initial drift was evaluated from the fluctuation of the response values generated by ISFETs which are immersed in saliva or aqueous solution. As a result, P7281-PU showed its suppression effect for the initial drift in the whole saliva and various solutions. Furthermore, the cause of drift may be H+ diffusion, and drift suppression effect of P7281-PU may be affected by urethane bond capturing H+ in ion-selective membrane. This result suggests a continuous nitrate monitoring and development of wearable sensors.

Background: IκBNS, a nuclear IκB protein, regulates a subset of Toll-like receptor (TLR) dependent genes. A cholate-containing high-fat diet (HFD(CA(+))) induces TLR4 mediated early inflammatory response. The present study aims to clarify that the lack of IκBNS promotes atherogenesis in low-density lipoprotein receptor-deficient (LDLr−/−) mice fed HFD(CA(+)) compared with those fed a cholate-free HFD (HFD(CA(−))). Methods and results: Mice that lacked IκBNS (IκBNS−/−) were crossed with LDLr−/− mice and formation of atherosclerotic lesions was analyzed after 6-week consumption of HFD(CA(+)) or HFD(CA(−)). IκBNS−/−/LDLr−/− mice fed HFD(CA(+)) (IκBNS−/−/LDLr−/−(CA(+))) showed a 3.5-fold increase of atherosclerotic lesion size in the aorta compared with LDLr−/−(CA(+)) mice (p

Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.

This study proposes the quantitative evaluation of mental workload for port-coordinator using NO₃ included in saliva, which is one of physiological indices. The NO₃ is secreted into blood and also blood-borne saliva when a human body receives the mental workload. So far the authors have tried a lot of evaluations based on a ship handling simulator; however, the authors still have not do firsthand experiments on a ship and in navigational environments. This study focuses on Hakata Port which is an ideal environment for an experimental scale. The authors were carried out an experiment for port-coordinators of Hakata Port Radio. The authors report the results of experiments.

IκBNS is a nuclear IκB protein which negatively regulates nuclear factor-κB activity. We demonstrated that IκBNS deficiency accelerates atherosclerosis in LDL receptor-deficient (LDLr−/−) mice via increased interleukin (IL)-6 production by macrophages. Previous studies showed that the increase in IL-6 might contribute to the development of atherosclerotic lesions. However, whether an anti-mouse IL-6 receptor antibody (MR16-1) can protect atherosclerotic lesions in atherogenic mice remains to be elucidated. We investigated atherosclerotic lesions in LDLr−/− and IκBNS−/−/LDLr−/− mice after 16 weeks consumption of a high-fat diet. All mice received intraperitoneal injections of MR16-1 or phosphate-buffered saline (PBS) (control) once a week during a high-fat diet consumption. Treatment of MR16-1 yielded no adverse systemic effects, and we detected no significant differences in serum cholesterol levels in either group. The atherosclerotic lesions were significantly increased in IκBNS−/−/LDLr−/− compared with LDLr−/− mice (p

We have investigated human-stress monitoring by making use of salivary nitrate, which can be a candidate for stress markers, with ion-selective field-effect transistors (ISFETs). ISFETs are suitable for on-site single-drop analysis of salivary nitrate within 10 s. However, when ISFETs are used for salivary nitrate, ISFETs have a problem that is called the initial drift. The initial drift makes accurate nitrate monitoring difficult. Thus, the purpose of this study is to prevent the initial drift and to search for a new, simple polymer to possess a better performance of sensor responses than conventional matrix membranes, such as PVC. In this research, we investigated ISFETs using specific matrix membranes, for example KP-13, Pellethane®­­, and P7281-PU. The initial drift was evaluated from the fluctuations of the response values generated by the ISFETs when immersed in saliva or aqueous solution. As a result, P7281-PU showed a prevention effect on the initial drift, both in the whole saliva and in various solutions. Furthermore, the cause of drift may be H+ diffusion, and the drift prevention effect of P7281-PU may be affected by urethane bond capturing H+ in the ion-selective membrane. This result suggests that a continuous nitrate monitoring is feasible and may be applied to wearable sensors.

Conductive atomic force microscope (C-AFM) writing is attracting attention as a technique which enables to clarify a switching mechanism of resistive random access memory (ReRAM) by providing a filament with large radius. We observed a C-AFM writing area of a NiO film using scanning electron microscope (SEM), and a correlation between contrast in a secondary electron image and a resistance written by C-AFM was confirmed. In addition, it was suggested that the resistance change effect occurred near the surface of the film. We also studied effects of a baking at low temperature and an electron irradiation with low electron energy on the resistance of the C-AFM writing area. As a result, it was suggested that the resistance change effect was caused by a defect-induced-distortion which is relaxed with low energy.

The Rapid Appearance and Disappearance of Dendriform Pulmonary Ossification after Diffuse Alveolar Hemorrhage Tomoko Yamagishi, Nobukazu Fujimoto, Yosuke Miyamoto, Naofumi Hara, Michiko Asano, Yasuko Fuchimoto, Sae Wada, Kenichi Kitamura, Shinji Ozaki, Hideyuki Nishi, and Takumi Kishimoto Department of Respiratory Medicine, Department of Medical Oncology, Department of Surgery, and Department of Internal Medicine, Okayama Rosai Hospital, Okayama, Japan

High load capacity of carburized gears originates mainly from the hardened layer and induced residual stress. On the other hand, surface decarburization, which causes a nonmartensitic layer, and inclusions such as oxides and segregation act as latent defects which considerably reduce fatigue strength. In this connection, the authors have proposed a formula of strength evaluation by separately quantifying defect influence. However, the principal defect which limits strength of gears with several different defects remains unclarified. This study presents a method of inferential identification of principal defects based on test results of carburized gears made of SCM420 clean steel, gears with both an artificial notch and nonmartensitic layer at the tooth fillet, and so forth. It clarifies practical uses of presented methods, and strength of carburized gears can be evaluated by focusing on principal defect size.

Recently, the idea that the resistance change phenomenon is caused by oxidation/reduction of the filament formed in the transition metal oxide has been widely accepted. However, it is difficult to cause the forming equally for every cell in a high-density memory cell array. Therefore, the existence of the forming is high barrier for resistive random access memory (ReRAM) to be put into practical use. In this paper, the initial resistance dependence of the reset current and the distribution of the forming and set voltages were investigated for the forming-free ReRAM cells, which start with the reset process. As a result, it was clarified that the reset current is proportional to the reciprocal of initial resistance independently of the film thickness and the film formation temperature. In addition, it was suggested that there are two kinds of filaments in the forming-free ReRAM. One is the filament which is completely restored by the first reset process. The other continues to operate even after the first reset.

The FcR common gamma-chain (FcRgamma) is an essential component of the receptors FcepsilonRI, FcgammaRI, and FcgammaRIII, which are expressed on many inflammatory cell types. The role of these receptors in the initiation or maintenance of allergic inflammation has not been well defined. FcRgamma-deficient (FcRgamma(-/-)) and control (wild-type (WT)) mice were sensitized and subsequently challenged with OVA. Following sensitization and challenge to OVA, FcRgamma-deficient (FcRgamma(-/-)) mice developed comparable levels of IgE and IgG1 as WT mice. However, numbers of eosinophils, levels of IL-5, IL-13, and eotaxin in bronchoalveolar lavage fluid, and mononuclear cell (MNC) proliferative responses to OVA were significantly reduced, as was airway hyperresponsiveness (AHR) to inhaled methacholine. Reconstitution of FcRgamma(-/-) mice with whole spleen MNC from WT mice before sensitization restored development of AHR and the numbers of eosinophils in bronchoalveolar lavage fluid; reconstitution after sensitization but before OVA challenge only partially restored these responses. These responses were also restored when FcRgamma(-/-) mice received T cell-depleted MNC, T and B cell-depleted MNC, or bone marrow-derived dendritic cells before sensitization from FcR(+/+) or FcgammaRIII-deficient but not FcRgamma(-/-) mice. The expression levels of FcgammaRIV on bone marrow-derived dendritic cells from FcR(+/+) mice were found to be low. These results demonstrate that expression of FcRgamma, most likely FcgammaRI, on APCs is important during the sensitization phase for the development of allergic airway inflammation and AHR.

S -carboxymethylcysteine ( S -CMC) has been used as a mucoregulator in respiratory diseases. However, the mechanism of action of S -CMC on allergic airway inflammation has not yet been defined. In the present study, BALB/c mice were initially sensitised and challenged to ovalbumin (OVA) and, weeks later, re-challenged with OVA (secondary challenge). S -CMC (5–100 mg·kg −1 ) was administered from 2 days before the secondary challenge through to the day of assay. Mice developed airway hyperresponsiveness (AHR) 6 h after the secondary challenge and increased numbers of neutrophils were present in the bronchoalveolar lavage (BAL) fluid. At 72 h after secondary challenge, mice again developed AHR, but the BAL fluid contained large numbers of eosinophils. S -CMC treatment was found to reduce AHR and neutrophilia at 6 h, as well as eosinophilia and AHR at 72 h. These effects appeared to be dose dependent. Goblet cell hyperplasia, observed at 72 h, was reduced by S -CMC. In BAL fluid, increased levels of interferon-γ, interleukin (IL)-12 and IL-10 and decreased levels of IL-5 and IL-13 were detected. In conclusion, the data indicate that S -carboxymethylcysteine is effective in reducing airway hyperresponsiveness and airway inflammation at two distinct phases of the response to the secondary allergen challenge in sensitised mice.

A physiological index is able to evaluate the mental workload of a ship's bridge teammate; a captain, a duty officer and a helmsman, sometime adding a pilot. The facial (nasal) temperature reads the mental workload well, and it has been confirmed by the past experiments; however, we do not evaluate a port coordinator, who supports to keep safe navigation in a bay and a harbour by supplying an useful information to a navigator, yet. The safe of bay and harbour is kept by teamwork among a ship, a government, and an agency and so on. We aim at the port coordinator in this study because their information is an important for safe navigation, and their mental workload shows the traffic condition of the bay and the harbour. Moreover, to understand their mental workload develops how to supply the useful and efficiency information to the vessels. In this study, we evaluate the nasal temperature while they serve as the port coordinator. The experiment is carried out at Hakata port radio. We show the nasal temperature is fine index to monitor their mental workload.

In order to determine the transcripts of gpI and gpIV of varicella-zoster virus (VZV), RNA was isolated from human embryonic fibroblast cells infected with VZV and Northern blot analysis was carried out using cloned DNA probes of unique short region including gpI and gpIV genes. The analysis of RNA revealed two discrete transcripts of 3.6 and 2.15 kilobases (kb) and three transcripts of 3.6, 2.9, and 1.6 kb which hybridized to DNA probes covering the gpI and gpIV region, respectively. Next, mRNAs were hybrid-selected, translated in vitro and the polypeptide products were immunoprecipitated with antibodies against these glycoproteins. The polypeptides with a molecular weight of 70,000 (70K) and 37K which were in vitro translational products of mRNA hybrid-selected with the DNA clone covering gpI and gpIV were detected using antibodies against gpI and gpIV, respectively. The result showed that the 70K polypeptide is presumably the translational product of 2.15 kb mRNA and the 37K polypeptide is that of 1.6 kb mRNA. DNA fragment encoding gpI or gpIV was inserted into vaccinia virus DNA and the recombinant viruses, mO74 (gpI) and mO39 (gpIV), were used for immunological analysis. In consequence, the gpI derived from cells infected with mO74 showed antigenic characteristics similar to those of gpI from VZV-infected cells as determined from the immunoprecipitation pattern, although the molecular weight of each polypeptide was different, and antibody produced in rabbits infected with recombinant virus had a high neutralizing activity, when the reaction was performed with complement. This suggested that gpI plays an important role for protection and recovery from VZV infection.