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Regulatory dendritic cells (DCregs) represent a potential therapeutic tool for assessing a variety of immune overreaction conditions; however, current approaches for generating DCregs for therapeutic purposes are limited. We attempted to generate and characterize DCregs from murine induced pluripotent stem (iPS) cells. The iPS cells co-cultured with OP9 cells displayed mesodermally differentiated flat colonies. GM-CSF drove most of the colonies exhibiting a differentiated morphology. Thereafter, cells became morphologically heterologous under the effects of TGF-β and IL-10. Most of the floating cells developed an irregular shape with areas of protrusion. The generated iPS-DCregs demonstrated high CD11b/c and low CD40, CD80, CD86 and MHC-II expressions with a high antigen uptake ability and poor T-cell stimulatory function. Importantly, iPS-DCregs showed immune responsiveness regulation effects both in vitro and in vivo and the ability to generate regulatory T-cells in vitro. Our result illustrates a feasible approach for generating functional DCregs from murine iPS cells. [ABSTRACT FROM AUTHOR]

Kawasaki disease complicates with myocarditis and vasculitis. Even if myocarditis is asymptomatic, heterogeneity of ventricular repolarization may be increased in the acute phase. We evaluated whether the change in repolarization characteristics can be used as a predictor for myocarditis and coronary lesions. Enrolled 34 children who were treated with intravenous immunoglobulin therapy. There were no sequelae in the recovery phase in any subjects, including those who had transient coronary artery lesion. QT and the interval from the Tpeak to Tend (Tp-e) were determined. The Tp-e/QT ratios were compared between the acute and recovery phases and correlations with CRP level and body temperature were evaluated. A retrospective evaluation of Tp-e/QT as predictors of coronary dilation was also performed. Tp-e/QT in the acute phase correlated positively with body temperature and CRP level. In a comparison of patients with and without transient coronary artery lesion, Tp-e/QT was significantly higher in those with dilation. In conclusion, Tp-e/QT was strongly related to transient coronary dilation, in comparison with inflammatory indicators including fever and CRP level. [ABSTRACT FROM AUTHOR]

Abstract: 5-Aminolevulinic acid (5-ALA) is the naturally occurring metabolic precursor of heme. Heme negatively regulates the Maf recognition element (MARE) binding- and repressing-activity of the Bach1 transcription factor through its direct binding to Bach1. Heme oxygenase (HO)-1 is an inducible enzyme that catalyzes the rate-limiting step in the oxidative degradation of heme to free iron, biliverdin and carbon monoxide. These metabolites of heme protect against apoptosis, inflammation and oxidative stress. Monocytes and macrophages play a critical role in the initiation, maintenance and resolution of inflammation. Therefore, the regulation of inflammation in macrophages is an important target under various pathophysiological conditions. In order to address the question of what is responsible for the anti-inflammatory effects of 5-ALA, the induction of HO-1 expression by 5-ALA and sodium ferrous citrate (SFC) was examined in macrophage cell line (RAW264 cells). HO-1 expression induced by 5-ALA combined with SFC (5-ALA/SFC) was partially inhibited by MEK/ERK and p38 MAPK inhibitor. The NF-E2-related factor 2 (Nrf2) was activated and translocated from the cytosol to the nucleus in response to 5-ALA/SFC. Nrf2-specific siRNA reduced the HO-1 expression. In addition, 5-ALA/SFC increased the intracellular levels of heme in cells. The increased heme indicated that the inactivation of Bach1 by heme supports the upregulation of HO-1 expression. Taken together, our data suggest that the exposure of 5-ALA/SFC to RAW264 cells enhances the HO-1 expression via MAPK activation along with the negative regulation of Bach1. [Copyright &y& Elsevier]

The need for standardized language is increasingly obvious, also within gastrointestinal endoscopy. A systematic approach to the description of endoscopic findings is vital for the development of a universal language, but systematic also means structured, and structure is inherently a challenge when presented as an alternative to the normal spoken word. The efforts leading to the "Minimal Standard Terminology" (MST) of gastrointestinal endoscopy offer a standardized model for description of endoscopic findings. With a combination of lesion descriptors and descriptor attributes, this system gives guidance to appropriate descriptions of lesions and also has a normative effect on endoscopists in training. The endoscopic report includes a number of items not related to findings per se, but to other aspects of the procedure, formal, technical, and medical. While the MST sought to formulate minimal lists for some of these aspects (e.g. indications), they are not all well suited for the inherent structure of the MST, and many are missing. Thus, the present paper offers a recommended standardization also of the administrative, technical, and other "periendoscopic" elements of the endoscopic report; important also are the numerous quality assurance initiatives presently emerging. Finally, the image documentation of endoscopic findings is becoming more obvious--and accessible. Thus, recommendations for normal procedures as well as for focal and diffuse pathology are presented. The recommendations are "minimal," meaning that expansions and subcategories will likely be needed in most centers. Still, with a stronger common grounds, communication within endoscopy will still benefit. [ABSTRACT FROM AUTHOR]

Hou J, Cai S, Kitajima Y, Fujino M, Ito H, Takahashi K, Abe F, Tanaka T, Ding Q, Li XK. 5-Aminolevulinic acid combined with ferrous iron induces carbon monoxide generation in mouse kidneys and protects from renal ischemia-reperfusion injury. Am J Physiol Renal Physiol 305: F1149-F1157, 2013. First published July 31, 2013; doi:10.1152/ajprenal.00275.2013.--Renal ischemia reperfusion injury (IRI) is a major factor responsible for acute renal failure. An intermediate in heme synthesis, 5-aminolevulinic acid (5-ALA) is fundamental in aerobic energy metabolism. Heme oxygenase (HO)-1 cleaves heme to form biliverdin, carbon monoxide (CO), and iron (Fe2+), which is used with 5-ALA. In the present study, we investigated the role of 5-ALA in the attenuation of acute renal IRI using a mouse model. Male Balb/c mice received 30 mg/kg 5-ALA with Fe2+ 48, 24, and 2 h before IRI and were subsequently subjected to bilateral renal pedicle occlusion for 45 min. The endogenous CO concentration of the kidneys from the mice administered 5-ALA/Fe2+ increased significantly, and the peak concentrations of serum creatinine and blood urea nitrogen decreased. 5-ALA/Fe2+ treatments significantly decreased the tubular damage and number of apoptotic cells. IRIinduced renal thiobarbituric acid-reactive substance levels were also significantly decreased in the 5-ALA/Fe2+ group. Furthermore, mRNA expression of HO-1, TNF-β, and interferon-γ was significantly increased after IRI. Levels of HO-1 were increased and levels of TNF-β and interferon-γ were decreased in the 5-ALA/Fe2+ pretreated renal parenchyma after IRI. F4/80 staining showed reduced macrophage infiltration, and TUNEL staining revealed that there were fewer interstitial apoptotic cells. These findings suggest that 5-ALA/ Fe2+ can protect the kidneys against IRI by reducing macrophage infiltration and decreasing renal cell apoptosis via the generation of CO. [ABSTRACT FROM AUTHOR]

Abstract: Background: QT interval variability provides information on ventricular vulnerability. However, QT interval variability in children has not been adequately evaluated. Methods: One hundred seventy-three consecutive nursing infants and children (male-female, 106:67) up to school age with no intrinsic cardiac disease were included in this study, and they were categorized into 6 age-related groups. The QT variability index (QTVI) was calculated based on an electrocardiogram; and age-specific standard values, sex-specific classification, and a standard growth curve covering 0 to 7 years were constructed. Results: The QTVI decreased in an age-dependent manner, reached constant values after school age, and exhibited no sex-specific differences in 6 age-related groups. Conclusions: Based on the age-dependent standardized QTVI values, it is possible to estimate the instability of ventricular repolarization in pediatric patients with better accuracy. [Copyright &y& Elsevier]

Kawasaki disease (KD) is an acute febrile disease of unknown etiology that develops in children and is sometimes accompanied by myocardial dysfunction and systemic vasculitis. However, myocardial repolarization lability has not yet been fully investigated. Thus, the objective of this study was to evaluate myocardial repolarization lability (QT variability index-QTVI) based on the body surface electrocardiograms in the acute and recovery phases. The subjects were 25 children with acute KD who were hospitalized for treatment. An equal number of age-matched healthy children were selected as controls. The RR-intervals and QT-intervals were measured based on a body surface electrocardiogram of 120 consecutive heartbeats to calculate the QTVI. The QTVI values were then compared with the acute and recovery phases. The relationships between blood biochemistry data and QTVI values were also examined. QTVI was significantly decreased from the acute phase to the recovery phase ( P < 0.05) and then recovered to the same level as that of the control. QTVI in the acute phase showed a significant positive relationship with body temperature and C-reactive protein ( P <0.05). QTVI was high in the acute phase and was correlated with an inflammatory reaction and became normalized during the recovery phase. [ABSTRACT FROM AUTHOR]