Bronchial asthma is an increasingly common disorder that remains poorly understood and difficult to manage. The disease is characterized by airway hyperresponsiveness, chronic inflammation, and mucus overproduction. Based on the finding that leukotriene B4 receptor 1 (BLT1) is expressed highly in Th2 lymphocytes, we analyzed the roles of BLT1 using an OVA-induced bronchial asthma model. BLT1-null mice did not develop airway hyperresponsiveness, eosinophilic inflammation, and hyperplasia of goblet cells. Attenuated symptoms were accompanied by reduced IgE production, and accumulation of IL-5 and IL-13 in bronchoalveolar lavage fluid, suggesting attenuated Th2-type immune response in BLT1-null mice. Peribronchial lymph node cells of sensitized BLT1-null mice showed much attenuated proliferation and production of Th2 cytokines upon re-stimulation with Ag in vitro. Thus, LTB4-BLT1 axis is required for the development of Th2-type immune response, and blockade of LTB4 functions through BLT1 would be novel and useful in the effort to ameliorate bronchial asthma and related Th2-biased immune disorders.
Plasma free amino acid (PFAA) profile is highlighted in its association with visceral obesity and hyperinsulinemia, and future diabetes. Indeed PFAA profiling potentially can evaluate individuals’ future risks of developing lifestyle-related diseases, in addition to diabetes. However, few studies have been performed especially in Asian populations, about the optimal combination of PFAAs for evaluating health risks. We quantified PFAA levels in 3,701 Japanese subjects, and determined visceral fat area (VFA) and two-hour post-challenge insulin (Ins120 min) values in 865 and 1,160 subjects, respectively. Then, models between PFAA levels and the VFA or Ins120 min values were constructed by multiple linear regression analysis with variable selection. Finally, a cohort study of 2,984 subjects to examine capabilities of the obtained models for predicting four-year risk of developing new-onset lifestyle-related diseases was conducted. The correlation coefficients of the obtained PFAA models against VFA or Ins120 min were higher than single PFAA level. Our models work well for future risk prediction. Even after adjusting for commonly accepted multiple risk factors, these models can predict future development of diabetes, metabolic syndrome, and dyslipidemia. PFAA profiles confer independent and differing contributions to increasing the lifestyle-related disease risks in addition to the currently known factors in a general Japanese population.
SummaryMetabolic complications associated with obesity are becoming more common among Japanese subjects. However, visceral fat accumulation is not always apparent by measuring body mass index (BMI) or waist circumference in Asian populations because of the physiological characteristics particular to those ethnicities. Excess visceral fat accumulation raises the odds ratio for developing cardiovascular disease. Thus, high-throughput determination of the amount of abdominal adipose tissue is necessary. We hypothesized that accumulating visceral fat alters the peripheral amino acid profile and that a multivariate logistic regression model of plasma free amino acids can distinguish visceral obesity. A total of 1449 Japanese subjects (985 males and 464 females) who had undergone a comprehensive health screening were enrolled in this study. The visceral fat area was determined using computed tomography imaging, and a plasma free amino acid index to identify high visceral fat areas (Ն100 cm 2 ) was developed. The sensitivity and specificity values of the generated amino acid index were 80% and 65%, respectively. In particular, the sensitivity of the generated index to identify subjects with non-apparent visceral obesity (BMI < 25 kg m -2 ; visceral fat area Ն 100 cm 2 ) was much greater than that of the waist circumference (73% vs. 46%, respectively). This index's high sensitivity and specificity may be the result of specific alterations in the patients' amino acid profiles, which were specifically correlated with the visceral fat areas and not with subcutaneous fat areas. This profile can be used as a predictor of elevated visceral obesity and a risk assessment tool for metabolic complications in Asian populations.Keywords: CT scan, high-throughput risk screening, non-apparent visceral obesity, plasma amino acid. What is already known about this subject• Asians with metabolic complications associated with obesity, a low body mass index and a low waist circumference have a greater proportion of visceral adipose tissue for a given amount of total body fat compared with Europeans.• Apparent obese humans and obese animal models show an elevation of branched-chain amino acid levels in plasma.• A multivariate logistic regression model of plasma free amino acids has been used to screen for several types of cancers in clinical settings. What this study adds• A specific formula incorporating six amino acid values (Ala, Gly, Glu, Trp, Tyr and branched-chain amino acid) was developed for discrimination of subjects with high visceral fat area by multivariate logistic regression analyses.• The generated amino acid formula was strongly correlated with visceral fat area in both apparent and non-apparent obese subjects.• Measuring plasma free amino acids can be used to distinguish the non-apparent visceral obesity in clinical settings in Asian populations.clinical obesity
A method for forming organic single-crystal arrays from solution is demonstrated using an organic semiconductor, 3,9-bis(4-ethylphenyl)-peri-xanthenoxanthene (C(2) Ph-PXX). Supersaturation of C(2) Ph-PXX/tetralin solution is spatially changed by making a large difference in solvent evaporation to generate nuclei at the designated location. The method is simple to implement since it employs only a micropattern and control of the solvent vapor pressure during growth.
The immune system has evolved numerous mechanisms of peripheral T cell immunoregulation, including a network of regulatory T (Treg) cells, to modulate and down-regulate immune responses at various times and locations and in various inflammatory circumstances. Amongst these, naturally occurring CD4(+)CD25(+) Treg cells (nTreg) represent a major lymphocyte population engaged in the dominant control of self-reactive T responses and maintaining tolerance in several models of autoimmunity. CD4(+)CD25(+) Treg cells differentiate in the normal thymus as a functionally distinct subpopulation of T cells bearing a broad T cell receptor repertoire, endowing these cells with the capacity to recognize a wide range of self and nonself antigen specificities. The generation of CD4(+)CD25(+) Treg cells in the immune system is genetically controlled, influenced by antigen recognition, and various signals, in particular, cytokines such as interleukin-2 and transforming growth factor-beta1, control their activation, expansion, and suppressive effector activity. Functional abrogation of these cells in vivo or genetic defects that affect their development or function unequivocally promote the development of autoimmune and other inflammatory diseases in animals and humans. Recent progress has shed light on our understanding of the cellular and molecular basis of CD4(+)CD25(+) Treg cell-mediated immune regulation. This article discusses the relative contribution of CD4(+)CD25(+) nTreg cells in the induction of immunologic self-tolerance and provides a comprehensive overview of recent finding regarding the functional properties and effector mechanism of these cells, as revealed from various in vitro and in vivo models.
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