Improvement of Sepsis by Hepatocyte Growth Factor, an Anti-Inflammatory Regulator: Emerging Insights and Therapeutic Potential

Sepsis-induced multiple organ failure (MOF) is the most frequent lethal disease in intensive care units. Thus, it is important to elucidate the self-defensive mechanisms of sepsis-induced MOF. Hepatocyte growth factor (HGF) is now recognized as an organotrophic factor, which is essential for organogenesis during embryonic growth and regeneration in adulthood. HGF production is enhanced in response to infectious challenges, but the increase in endogenous HGF levels is transient and insufficient, with a time lag between tissue injuries and HGF upregulation, during progression of septic MOF. Thus, administration of active-formed HGF might be a new candidate for therapeutic development of MOF. HGF has an ability to target endotoxin-challenged macrophages and inhibits the upregulation of inflammatory cytokines through nuclear factor-κB-inactivated mechanisms. HGF also targets the endothelium and epithelium of various organs to suppress local inflammation, coagulation, and apoptotic death. This paper summarizes the novel mechanisms of HGF for attenuating sepsis-related pathological conditions with a focus on sepsis-induced MOF

A DEVELOPMENT OF A MUA TO MAKE PICTOGRAPH MAIL FOR CHILDREN

In recent years, children have begun using computers actively. With this situation, they are beginning to learn how to operate a mail user agent (Hereafter, called MUA) to adaptation to an information society. However, the user interface of general MUAs is not designed with them in mind. Specifically, many unnecessary menu items exist on the user interface of general MUAs. Moreover, the menu text contains many difficult characters (called Kanji) in Japan. In this situation, it is difficult to say that children could learn how to operate the MUA without being confused by the complex user interface. We consider it to be important that even children who have not learned Kanji can use the user interface. To solve this issue, we have developed a MUA that has a simple user interface only represented in Hiragana. In order to create a simple user interface for child use, it is necessary to reduce the number of menu items. Along with this, the number of available functions on this MUA has decreased. However, we think it is rather important to prevent the confusion and unexpected behavior of children. It is also necessary to devise a function to make an e-mail to attract the interest of them. Therefore, we have implemented a function to generate pictograph mail easily.We are using the XML-based User Interface Language (Hereafter, called XUL) to build a user interface for children. It is a language used to build the user interface of Mozilla applications like Firefox and Thunderbird. By using it, we can customize the user interface of Thunderbird to fit any purpose. By these improvements, we think children will be able to use the MUA actively and with enjoyment without falling into confusion

Suzaku Observations of M82 X-1 : Detection of a Curved Hard X-ray Spectrum

A report is presented on Suzaku observations of the ultra-luminous X-ray source X-1 in the starburst galaxy M82, made three time in 2005 October for an exposure of ~ 30 ks each. The XIS signals from a region of radius 3 around the nucleus defined a 2-10 keV flux of 2.1 x 10^-11 erg s-1 cm-2 attributable to point sources. The 3.2-10 keV spectrum was slightly more convex than a power-law with a photon index of 1.7. In all observations, the HXD also detected signals from M82 up to ~ 20 keV, at a 12-20 keV flux of 4.4 x 10^-12 erg s-1 cm-2 . The HXD spectrum was steeper than that of the XIS. The XIS and HXD spectra can be jointly reproduced by a cutoff power-law model, or similar curved models. Of the detected wide-band signals, 1/3 to 2/3 are attributable to X-1, while the remainder to other discrete sources in M82. Regardless of the modeling of these contaminants, the spectrum attributable to X-1 is more curved than a power-law, with a bolometric luminosity of (1.5 -3) x 10 ^40 erg s-1. These results are interpreted as Comptonized emission from a black hole of 100-200 solar masses, radiating roughly at the Eddington luminosity.Comment: 19 pages, 9 figures, accepted in Publications of the Astronomical Society of Japa

Tryptophan 2,3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice

Although nutrients, including amino acids and their metabolites such as serotonin (5-HT), are strong modulators of anxiety-related behavior, the metabolic pathway(s) responsible for this physiological modulation is not fully understood. Regarding tryptophan (Trp), the initial rate-limiting enzymes for the kynurenine pathway of tryptophan metabolism are tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO). Here, we generated mice deficient for tdo (Tdo-/-). Compared with wild-type littermates, Tdo-/- mice showed increased plasma levels of Trp and its metabolites 5-hydroxyindoleacetic acid (5-HIAA) and kynurenine, as well as increased levels of Trp, 5-HT and 5-HIAA in the hippocampus and midbrain. These mice also showed anxiolytic modulation in the elevated plus maze and open field tests, and increased adult neurogenesis, as evidenced by double staining of BrdU and neural progenitor/neuronal markers. These findings demonstrate a direct molecular link between Trp metabolism and neurogenesis and anxiety-related behavior under physiological conditions

Wide-band spectroscopy of the Compton thick Seyfert 2 galaxy Mrk 3 with Suzaku

We obtained a wide-band spectrum of the Compton-thick Seyfert 2 galaxy Mrk 3 with Suzaku. The observed spectrum was clearly resolved into weak, soft power-law emission, a heavily absorbed power-law component, cold reflection, and many emission lines. The heavily absorbed component, absorbed by gas with a column density of 1.1x10^24 cm^-2, has an intrinsic 2--10 keV luminosity of ~1.6x10^43 erg s^-1, and is considered to be direct emission from the Mrk 3 nucleus. The reflection component was interpreted as reflection of the direct light off cold, thick material; the reflection fraction $R$ was 1.36+/-0.20. The cold material is inferred to be located > 1 pc from the central black hole of Mrk 3 due to the low ionization parameter of iron (xi < 1 erg cm s^-1) and the narrow iron line width (s < 22 eV). A Compton shoulder to the iron line was detected, but the intensity of the shoulder component was less than that expected from spherically distributed Compton-thick material. The weak, soft power-law emission is considered to be scattered light by ionized gas. The existence of many highly-ionized lines from O, Ne, Mg, Si, S, and Fe in the observed spectrum indicates that the ionized gas has a broad ionized structure, with xi=10--1000. The scattering fraction with respect to the direct light was estimated to be 0.9+/-0.2%, which indicates that the column density of the scattering region is about 3.6x10^22 cm^-2. This high-quality spectrum obtained by Suzaku can be considered a template for studies of Seyfert 2 galaxies.Comment: 24 pages, 8 figures, accepted in PASJ for publicatio

Solar urticaria: clinical characteristics, treatment effectiveness, long-term prognosis, and QOL status in 29 patients

IntroductionSolar urticaria (SU), a relatively rare skin inflammatory and photosensitivity disease, is often resistant to standard urticaria treatment. Quality of life (QOL) among SU patients has not been extensively explored. This study was performed to clarify the clinical features and effectiveness of therapies (e.g., hardening therapy) for SU and to determine QOL among SU patients.MethodsThe authors examined the characteristics, treatments, and QOL statuses of 29 Japanese SU patients using medical records and a questionnaire approach.ResultsAmong 29 patients, H1 antihistamine therapy (H1) was effective in 22 (75.8%) patients. H2 antihistamine therapy (H2) was effective in three of seven (42.9%) patients. Ultraviolet radiation A (UVA) hardening therapy was effective in eight of nine (88.9%) patients. Visible light (VL) hardening therapy was ineffective in three of three patients. In one patient who underwent both UVA and VL hardening therapy, only UVA hardening therapy was effective. In the questionnaire, 18 patients (90%) reported some improvement compared with disease onset (four had complete remission, six had completed treatment although mild symptoms persisted, and eight were receiving treatment with moderate symptoms), whereas two patients reported exacerbation. Patients in complete remission had a mean disease duration of 4 years, whereas patients not in remission had a mean disease duration of 8.8 years. The mean Dermatology Life Quality Index (DLQI) score for the current status was 7.4. There was a correlation between DLQI and symptom/treatment status. However, neither DLQI and action spectra nor DLQI and treatments exhibited significant differences.DiscussionThe questionnaire revealed current QOL status and long-term prognosis in SU patients. Compared with disease onset, most patients showed improvement when assessed for this study. Both H1 and H2 should be attempted for all SU patients. UVA hardening therapy may be an option for SU patients with an action spectrum that includes UVA