Working ability between air and trimix breathing gas under 8 ATA air condition

Pneumatic caisson work in Japan has come into operation since 1924. Afterward, this technique of compressed air work has been widely utilized in the construction of foundation basements, shafts of the bottom tunnel shields for subway and so forth. While using this technique of compressed air work means that workers have to be exposed to hyperbaric environment, this technique has risks of not only decompression sickness (DCS) but also toxicity of poisonous gas and/or oxygen deficiency. However, this technique is independent of city construction work and the operation of compressed air work higher than 5ATA (4.0 kg/cm2G) is actually been planning recently. Accordingly unmanned caisson work is considered as a better technique for such higher pressurized work, even though workers must enter into hyperbaric working fields for maintenance or repair of unmanned operated machinery and materials. This research is to establish the safe work under hyperbaric air environment at 8ATA.     

Changes in the fluorescence parameters of bound N-(1-pyrene) maleimide by lipid peroxidation of intestinal brush-border membranes

Using a fluorogenic thiol reagent, N-(1-pyrene)maleimide (NPM), we have examined of lipid peroxidation on the microenvironment around SH groups of the membrane proteins in porcine intestinal brush-border membrane vesicles. The lipid peroxidation of the membranes was performed with various concentrations of t-butylhydroperoxide (t-BuOOH) in the presence of 100 microM ascorbic acid and 10 microM Fe2+. Treatment of NPM-labeled membranes with these oxidizing agents resulted in a decrease of the fluorescence lifetime, suggesting modification of the environmental properties around the bound dye. Measurement of the steady-state fluorescence anisotropy of the labeled membranes indicated restriction of the motion of the bound dye by the lipid peroxidation membranes. This interpretation was further supported by an elevation of the transition temperature of the anisotropy, a decrease in the quenching rate constant of the fluorescence with acrylamide and a decrease in the SH reactivity of the membrane proteins for NPM by lipid peroxidation. Based on these results, the possibility of conformation changes in the vicinity of SH groups in the membrane proteins associated with lipid peroxidation has been discussed.     

Progressively Increased M50 Responses to Repeated Sounds in Autism Spectrum Disorder with Auditory Hypersensitivity: A Magnetoencephalographic Study

The aim of this study was to investigate the differential time-course responses of the auditory cortex to repeated auditory stimuli in children with autism spectrum disorder (ASD) showing auditory hypersensitivity. Auditory-evoked field values were obtained from 21 boys with ASD (12 with and 9 without auditory hypersensitivity) and 15 age-matched typically developing controls. M50 dipole moments were significantly increased during the time-course study only in the ASD with auditory hypersensitivity compared with those for the other two groups. The boys having ASD with auditory hypersensitivity also showed more prolonged response duration than those in the other two groups. The response duration was significantly related to the severity of auditory hypersensitivity. We propose that auditory hypersensitivity is associated with decreased inhibitory processing, possibly resulting from an abnormal sensory gating system or dysfunction of inhibitory interneurons.     

Gap Effect Abnormalities during a Visually Guided Pro-Saccade Task in Children with Attention Deficit Hyperactivity Disorder

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that starts in early childhood and has a comprehensive impact on psychosocial activity and education as well as general health across the lifespan. Despite its prevalence, the current diagnostic criteria for ADHD are debated. Saccadic eye movements are easy to quantify and may be a quantitative biomarker for a wide variety of neurological and psychiatric disorders, including ADHD. The goal of this study was to examine whether children with ADHD exhibit abnormalities during a visually guided pro-saccadic eye-movement and to clarify the neurophysiological mechanisms associated with their behavioral impairments. Thirty-seven children with ADHD (aged 5–11 years) and 88 typically developing (TD) children (aged 5–11 years) were asked to perform a simple saccadic eye-movement task in which step and gap conditions were randomly interleaved. We evaluated the gap effect, which is the difference in the reaction time between the two conditions. Children with ADHD had a significantly longer reaction time than TD children (p < 0.01) and the gap effect was markedly attenuated (p < 0.01). These results suggest that the measurement of saccadic eye movements may provide a novel method for evaluating the behavioral symptoms and clinical features of ADHD, and that the gap effect is a potential biomarker for the diagnosis of ADHD in early childhood.     

Sc237 hamster PrPSc and Sc237-derived mouse PrPSc generated by interspecies in vitro amplification exhibit distinct pathological and biochemical properties in tga20 transgenic mice

Prions are the infectious agents responsible for transmissible spongiform encephalopathy, and are primarily composed of the pathogenic form (PrP(Sc)) of the host-encoded prion protein (PrP(C)). Recent studies have revealed that protein misfolding cyclic amplification (PMCA), a highly sensitive method for PrP(Sc) detection, can overcome the species barrier in several xenogeneic combinations of PrP(Sc) seed and PrP(C) substrate. Although these findings provide valuable insight into the origin and diversity of prions, the differences between PrP(Sc) generated by interspecies PMCA and by in vivo cross-species transmission have not been described. This study investigated the histopathological and biochemical properties of PrP(Sc) in the brains of tga20 transgenic mice inoculated with Sc237 hamster scrapie prion and PrP(Sc) from mice inoculated with Sc237-derived mouse PrP(Sc), which had been generated by interspecies PMCA using Sc237 as seed and normal mouse brain homogenate as substrate. Tga20 mice overexpressing mouse PrP(C) were susceptible to Sc237 after primary transmission. PrP(Sc) in the brains of mice inoculated with Sc237-derived mouse PrP(Sc) and in the brains of mice inoculated with Sc237 differed in their lesion profiles and accumulation patterns, Western blot profiles, and denaturant resistance. In addition, these PrP(Sc) exhibited distinctive virulence profiles upon secondary passage. These results suggest that different in vivo and in vitro environments result in propagation of PrP(Sc) with different biological properties.     

Assessment of prion inactivation by combined use of Bacillus-derived protease and SDS

Prions, infectious agents causing transmissible spongiform encephalopathy, retain infectivity even after undergoing routine sterilization processes. We found that MSK103 protease, identified in our previous study, effectively reduces infectivity and the level of misfolded isoform of the prion protein in scrapie-infected brain homogenates in the presence of SDS. The treatment therefore can be applied to the decontamination of thermolabile instruments.     

In Vivo Characterization of Neutrophil Extracellular Traps in Various Organs of a Murine Sepsis Model

Neutrophil extracellular traps (NETs) represent extracellular microbial trapping and killing. Recently, it has been implicated in thrombogenesis, autoimmune disease, and cancer progression. The aim of this study was to characterize NETs in various organs of a murine sepsis model in vivo and to investigate their associations with platelets, leukocytes, or vascular endothelium. NETs were classified as two distinct forms; cell-free NETs that were released away from neutrophils and anchored NETs that were anchored to neutrophils. Circulating cell-free NETs were characterized as fragmented or cotton-like structures, while anchored NETs were characterized as linear, reticular, membranous, or spot-like structures. In septic mice, both anchored and cell-free NETs were significantly increased in postcapillary venules of the cecum and hepatic sinusoids with increased leukocyte-endothelial interactions. NETs were also observed in both alveolar space and pulmonary capillaries of the lung. The interactions of NETs with platelet aggregates, leukocyte-platelet aggregates or vascular endothelium of arterioles and venules were observed in the microcirculation of septic mice. Microvessel occlusions which may be caused by platelet aggregates or leukocyte-platelet aggregates and heterogeneously decreased blood flow were also observed in septic mice. NETs appeared to be associated with the formation of platelet aggregates or leukocyte-platelet aggregates. These observational findings may suggest the adverse effect of intravascular NETs on the host during a sepsis.     

The Inhibition of N-Glycosylation of Glycoprotein 130 Molecule Abolishes STAT3 Activation by IL-6 Family Cytokines in Cultured Cardiac Myocytes

Interleukin-6 (IL-6) family cytokines play important roles in cardioprotection against pathological stresses. IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. In cardiomyocytes, the treatment with Tm completely replaced the glycosylated form of gp130 with its unglycosylated one. Tm treatment inhibited leukemia inhibitory factor (LIF)-mediated activation of STAT3 and ERK1/2. Similarly, IL-11 failed to activate STAT3 and ERK1/2 in the presence of Tm. Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. To exclude the possibility that Tm blocks LIF and IL-11 signals by inhibiting the glycosylation of their specific receptors, we investigated whether the stimulation with IL-6 plus soluble IL-6 receptor (sIL-6R) could transduce their signals in Tm-treated cardiomyocytes and found that this stimulation was unable to activate the downstream signals. Collectively, these findings indicate that glycosylation of gp130 is essential for signal transduction of IL-6 family cytokines in cardiomyocytes.