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Background: Mast cells play a central role in allergic and inflammatory diseases. Several reports indicated role of peroxisome proliferator-activated receptor gamma (PPARγ) on mast cell function. However, there is no report about the role of PPARγ on differentiation of mast cells from the progenitors. In this study, we investigated the role of PPARγ in regulating bone marrow-derived mast cell maturation and the therapeutic implications for mast cell-related diseases such as atopic or contact dermatitis. Methods: We used in vitro cell culture system for mast cell differentiation from bone marrow-progenitors using specific ligands and lentiviral-mediated short hairpin RNA of PPARγ, and in vivo murine dermatitis models. Results: Activation of PPARγ inhibited the maturation of bone marrow progenitors into connective tissue-type mast cells (CTMCs) through up-regulation of GATA-4 and GATA-6 resulting in a decrease in expression of histidine decarboxylase and mast cell histamine content. In comparison, the differentiation of bone marrow progenitors into CTMCs was significantly accelerated by the knockdown of PPARγ expression by lentiviral-mediated short hairpin RNA. Peroxisome proliferator-activated receptor gamma ligand administration to mice inhibited the maturation of mast cells resulting in attenuation of atopic and contact dermatitis via diminishment of the number of mature mast cells. Conclusion: Our results indicate that PPARγ is one of master regulators on mast cell maturation and potentially useful for the therapy in various disorders involving mast cell activation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Crescent formation in the renal glomerulus is a typical manifestation of progressive glomerulopathy associated with fatal renal failure; therefore, its prevention is of clinical importance. Little is known about the pathogenic mechanism for crescent formation. This study was undertaken in an attempt to identify the events that are critical for crescent formation in immune complex crescentic glomerulonephritis (CGN) by analyzing a novel mutant strain of mice. METHODS: A spontaneous mutant strain of mice was isolated from the autoimmune-prone strain EOD, which stably develops fatal CGN. The mutant phenotypes were assessed histopathologically, hematologically, and immunologically. The mutation was searched for with positional cloning using microsatellite markers. RESULTS: Compared with wild-type EOD (WT-EOD) mice, mutant EOD (mut-EOD) mice showed marked improvement in CGN in conjunction with an improvement in spontaneous mortality. In WT-EOD mice, an inverse correlation between blood urea nitrogen concentration and blood platelet count and massive accumulation of platelets in the glomerulus were evident, suggesting that an accumulation of platelets in the glomerulus contributes to the progression of CGN. The mutant platelets showed an abnormal aggregation in response to collagen and thrombin, associated with a bleeding tendency in mut-EOD mice. Genetic analysis revealed a deleterious mutation in the cappuccino gene (cno), which encodes a protein that belongs to a complex called the biogenesis of lysosome-related organelle complex 1 and is profoundly involved in platelet function. Morphologic examination revealed a partial defect in dense body formation in the delta-granule of platelets. CONCLUSION: The present findings suggest that platelet functions have a critical role in crescent formation in autoimmune GN. [ABSTRACT FROM AUTHOR]

Bacillus cereus (B. cereus) meningitis sometimes occurs in patients with risk factors, which are associated with central nervous system (CNS) anomalies, surgical or anaesthetic access to CNS. We observed two cases of B. cereus meningitis in neonates without such risk factors. The clinical courses of both neonates were fulminant, and routine antibiotic therapy failed. Intracranial haemorrhage was evident at autopsy. According to the previous neonatal case reports and our experience, we found that six of seven neonates were premature babies admitted to the neonatal intensive care unit, five died within a week of onset of the disease, and six had intracranial haemorrhage. We speculate that B. cereus meningitis may occur in neonates, even without any of the risk factors previously described in adult case reports, and that the clinical manifestations of the meningitis might be characterized by the high incidence of intracranial haemorrhage and poor mortality. [ABSTRACT FROM AUTHOR]