Impact of Diesel Exhaust Particles on Th2 Response in the Lung in Asthmatic Mice

Although it has been accepted that pulmonary exposure to diesel exhaust particles (DEP), representative constituents in particulate matter of mass median aerodynamic diameter < or 2.5 µm (PM2.5), exacerbates murine allergic asthma, the in vivo effects of DEP on their cellular events in the context of allergen-specific Th response have never been examined. The aim of this study is to elucidate whether in vivo repetitive exposure to DEP combined with allergen (ovalbumin) facilitate allergen-specific Th response in the lung using a simple ex vivo assay system. As a result, repetitive pulmonary exposure to DEP in vivo, if combined with allergen, amplifies ex vivo allergen-specific Th2 response in the lung compared to that to allergen alone, characterized by high levels of interleukin (IL)-4 and IL-5. The result suggests that in asthmatic subjects, DEP promote Th2-prone milieu in the lung, which additively/synergistically augment asthma pathophysiology in vivo

Extensive Analysis of Elastase-Induced Pulmonary Emphysema in Rats: ALP in the Lung, a New Biomarker for Disease Progression?

It is accepted that pulmonary exposure of rodents to porcine pancreatic elastase (ELT) induces lesions that morphologically resemble human emphysema. Nonetheless, extensive analysis of this model has rarely been conducted. The present study was designed to extensively examine the effects of ELT on lung inflammation, cell damage, emphysematous change, and cholinergic reactivity in rats. Intratracheal administration of two doses of ELT induced 1) a proinflammatory response in the lung that was characterized by significant infiltration of macrophages and an increased level of interleukin-1β in lung homogenates, 2) lung cell damage as indicated by higher levels of total protein, lactate dehydrogenase, and alkaline phosphatase (ALP) in lung homogenates, 3) emphysema-related morphological changes including airspace enlargement and progressive destruction of alveolar wall structures, and 4) airway responsiveness to methacholine including an augmented Rn value. In addition, ELT at a high dose was more effective than that at a low dose. This is the novel study to extensively analyze ELT-induced lung emphysema, and the analysis might be applied to future investigations that evaluate new therapeutic agents or risk factors for pulmonary emphysema. In particular, ALP in lung homogenates might be a new biomarker for the disease progression/exacerbation

Searching for the most distant blazars with the Fermi Gamma-ray Space Telescope

We investigate the prospects for discovering blazars at very high-redshifts (z>3-6) with the Fermi Gamma-Ray Space Telescope (Fermi), employing a model for the evolving gamma-ray luminosity function (GLF) of the blazar population. Our previous GLF model is used as a basis, which features luminosity-dependent density evolution implied from X-ray data on active galactic nuclei, as well as the blazar sequence paradigm for their spectral energy distribution, and which is consistent with EGRET and current Fermi observations of blazars.Here we augment the high-redshift evolution of this model by utilizing the luminosity function of quasars from the Sloan Digital Sky Survey (SDSS), which is well-constrained up to z~5. We find that Fermi may discover a few blazars up to z~6 in the entire sky during its 5-year survey. We further discuss how such high-redshift blazar candidates may be efficiently selected in future Fermi data.Comment: 6 pages, 2 figures, accepted for publication in MNRA

Multi-physics Extension of OpenFMO Framework

OpenFMO framework, an open-source software (OSS) platform for Fragment Molecular Orbital (FMO) method, is extended to multi-physics simulations (MPS). After reviewing the several FMO implementations on distributed computer environments, the subsequent development planning corresponding to MPS is presented. It is discussed which should be selected as a scientific software, lightweight and reconfigurable form or large and self-contained form.Comment: 4 pages with 11 figure files, to appear in the Proceedings of ICCMSE 200

Phenotyping of P105-Negative B Cell Subsets in Patients with Systemic Lupus Erythematosus

This study aimed to investigate phenotype of RP105(−) B cell subsets in patients with systemic lupus erythematosus (SLE). Flow cytometry was used for phenotyping RP105-negaive B cell subsets. Based on CD19, RP105, and CD138 expression, RP105(−) B cells consist of at least 5 subsets of late B cells, including CD19(+)RP105(int), CD19(+) RP105(−), CD19(low) RP105(−) CD138(−), CD19(low) RP105(−)CD138(int), and CD19(low) RP105(−) CD138(++) B cells. Especially, CD19(+)RP105(int) and CD19(low) RP105(−)CD138(int) B cells are significantly larger than other RP105(−) B cell subsets in SLE. By comparison of RP105(−) B cell subsets between patients with SLE and normal subjects, these subsets were detectable even in normal subjects, but the percentages of RP105(−) B cell subsets were significantly larger in SLE. The phenotypic analysis of RP105(−) B cell subsets suggests dysregulation of later B cell subsets in SLE and may provide new insights into understanding regulation of B cells in human SLE

Perfluorooctane Sulfonate (PFOS) and Related Perfluorinated Compounds in Human Maternal and Cord Blood Samples: Assessment of PFOS Exposure in a Susceptible Population during Pregnancy

Fluorinated organic compounds (FOCs), such as perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorooctane sulfonylamide (PFOSA), are widely used in the manufacture of plastic, electronics, textile, and construction material in the apparel, leather, and upholstery industries. FOCs have been detected in human blood samples. Studies have indicated that FOCs may be detrimental to rodent development possibly by affecting thyroid hormone levels. In the present study, we determined the concentrations of FOCs in maternal and cord blood samples. Pregnant women 17–37 years of age were enrolled as subjects. FOCs in 15 pairs of maternal and cord blood samples were analyzed by liquid chromatography–electrospray mass spectrometry coupled with online extraction. The limits of quantification of PFOS, PFOA, and PFOSA in human plasma or serum were 0.5, 0.5, and 1.0 ng/mL, respectively. The method enables the precise determination of FOCs and can be applied to the detection of FOCs in human blood samples for monitoring human exposure. PFOS concentrations in maternal samples ranged from 4.9 to 17.6 ng/mL, whereas those in fetal samples ranged from 1.6 to 5.3 ng/mL. In contrast, PFOSA was not detected in fetal or maternal samples, whereas PFOA was detected only in maternal samples (range, < 0.5 to 2.3 ng/mL, 4 of 15). Our results revealed a high correlation between PFOS concentrations in maternal and cord blood (r(2) = 0.876). However, we did not find any significant correlations between PFOS concentration in maternal and cord blood samples and age bracket, birth weight, or levels of thyroid-stimulating hormone or free thyroxine. Our study revealed that human fetuses in Japan may be exposed to relatively high levels of FOCs. Further investigation is required to determine the postnatal effects of fetal exposure to FOCs