The presence of histamine and eosinophil cationic protein in nasopharyngeal secretions of infants with respiratory syncytial virus (RSV)-induced bronchiolitis implies the activation of basophil and eosinophil leukocytes, but the specific mechanism of their recruitment has not been elucidated. Chemokines are potent and selective leukocyte chemotactic molecules that are also expressed by airway epithelial cells. Therefore, the pattern of chemokines produced in response to RSV infection was investigated in primary cultures of human nose- and adenoid-derived epithelial cells. Interleukin-8, growth-related peptide-alpha, and monocyte chemotactic protein-1 were constitutively released by uninfected epithelial cells and were not further enhanced by infection with RSV. RANTES (regulated upon activation, normal T cell-expressed and -secreted), which was present in negligible concentrations in uninfected cultures, was strongly induced by RSV infection, in a dose- and time-dependent manner. Through the release of RANTES, epithelial cells may control the selective concentration and activation of basophils and eosinophils in RSV-infected airway mucosa.

Respiratory syncytial virus (RSV) is the major cause of acute bronchiolitis in infancy, a syndrome characterized by wheezing, respiratory distress, and the pathologic findings of peribronchial mononuclear cell infiltration and release of inflammatory mediators by basophil and eosinophil leukocytes. Composition and activation of this cellular response are thought to rely on the discrete target cell selectivity of C-C chemokines. We demonstrate that infection in vitro of human epithelial cells of the lower respiratory tract by RSV induced dose- and time-dependent increases in mRNA and protein secretion for RANTES (regulated upon activation, normal T-cell expressed and presumably secreted), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α). Production of MCP-1 and MIP-1α was selectively localized only in epithelial cells of the small airways and lung. Exposure of epithelial cells to gamma interferon (IFN-γ), in combination with RSV infection, induced a significant increase in RANTES production that was synergistic with respect to that obtained by RSV infection or IFN-γ treatment alone. Epithelial cell-derived chemokines exhibited a strong chemotactic activity for normal human blood eosinophils. Furthermore, eosinophils were susceptible to RSV and released RANTES and MIP-1α as a result of infection. Therefore, the inflammatory process in RSV-induced bronchiolitis appears to be triggered by the infection of epithelial cells and further amplified via mechanisms driven by IFN-γ and by the secretion of eosinophil chemokines.

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Summary:Accidental exposure to acute high-dose total body neutron radiation is rare. We report a 35-year-old man exposed to a total body dose of 5.4 Gy neutron-and 8.5-13 Gy ␥-radiation in a radiation criticality accident. He received a blood stem cell transplant from his HLAidentical sister. There was bone marrow recovery with complete donor chimerism. Random chromatid breaks were observed in donor cells suggesting a bystander effect of neutron exposure. The subject died 82 days after the accident (75 days post transplant) from multiorgan failure. Bone Marrow Transplantation (2002) 29, 935-939.

Extracranial carotid aneurysm caused by Takayasu's arteritis is extremely rare. We have experienced six cases of extracranial carotid aneurysm among 106 cases of Takayasu's arteritis that were treated surgically in the past 50 years. We herein review these cases and discuss the surgical indications and postoperative course of this rare disease. We report original observations about extracranial carotid aneurysm in Takayasu's arteritis.

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How the pluripotency of stem cells is maintained and the role of transcription factors in this maintenance remain major questions. In the present study, in order to clarify the mechanism underlying the pluripotency of stem cells for the advancement of regenerative medicine, we examined the effect of forced Nanog expression in mesenchymal cells, with a particular focus on osteogenic differentiation. The human mesenchymal stromal cells (hMSCs) or mouse mesenchymal cell line C3H10T1/2 cells were transduced with the Nanog gene or control green fluorescent protein (GFP) gene by using retrovirus vectors. Short-term, forced Nanog gene expression had few effects on the terminal osteogenic differentiation of either hMSCs or C3H10T1/2 cells. To determine its long-term effects, we established C3H10T1/2 cells expressing Nanog constitutively. Constitutive Nanog expression strongly induced osteogenic differentiation of C3H10T1/2 cells. In regard to cell proliferation, constitutive Nanog expression only repressed the proliferation of the cells treated with rhBMP-2. Moreover, Nanog also had the potential to promote the proliferation of C3H10T1/2 cells in the absence of rhBMP-2. Constitutive Nanog expression enhanced phosphorylation of Smad1/5/8 and suppressed Cdk4 and cyclinD1. The promoter activities of both the osteocalcin and Id-1 genes were activated in cells expressing Nanog constitutively. To identify downstream molecules of Nanog involved in the promotion of osteogenic differentiation, we performed a DNA microarray analysis and discovered that NFATc1 was one of the downstream effectors of Nanog. These results indicate that Nanog functions as a modulator of BMP signaling in C3H10T1/2 cells probably through a genome reprogramming process.

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