In this study, the authors assessed air quality and health effects of the 1997 haze disaster in Indonesia. The authors measured carbon monoxide, carbon dioxide, sulfur dioxide, nitrogen dioxide, ozone, particulate matter with diameters less than or equal to 10 microm, inorganic ions, and polycyclic aromatic hydrocarbons. The authors also interviewed 543 people and conducted lung-function tests and determined spirometric values for these individuals. Concentrations of carbon monoxide and particulate matter with diameters less than or equal to 10 microm reached "very unhealthy" and "hazardous" levels, as defined by the Pollution Standards Index. Concentrations of the polycyclic aromatic hydrocarbons were 6-14 times higher than levels in the unaffected area. More than 90% of the respondents had respiratory symptoms, and elderly individuals suffered a serious deterioration of overall health. In multivariate analysis, the authors determined that gender, history of asthma, and frequency of wearing a mask were associated with severity of respiratory problems. The results of our study demonstrate the need for special care of the elderly and for care of those with a history of asthma. In addition, the use of a proper mask may afford protection.

The transcription factor FoxN1 is essential for differentiation of thymic epithelial cell (TEC) progenitors during thymic organogenesis. However, limited information is available on the postnatal contribution of FoxN1 to thymic maintenance. To address this question, we generated a loxP-floxed FoxN1 (fx) mouse with three different promoter-driven inducible CreER T transgenes. Postnatal ubiquitous deletion of FoxN1 caused dramatic thymic atrophy in 5 days and more severe deterioration in medullary TECs (mTECs) than in cortical TECs (cTECs). Induction of FoxN1 deletion selectively in K5 promoter-driven somatic epithelial cells (mostly mTECs and possibly some adult epithelial stem cells) was sufficient to cause significant thymic atrophy, whereas FoxN1 deletion in K18 promoter-driven somatic epithelial cells (mostly cTECs) was not. Thymic atrophy resulted from increased apoptosis and was associated with activation of the p53 gene in mature mTECs. Although FoxN1 is required for the development of both mTECs and cTECs in thymic organogenesis, it is most important for the maintenance of mTECs in the postnatal thymus, which are in turn necessary to prevent thymic atrophy.The thymus gland is not only required for ontogenesis but is also indispensable for postnatal cellular immune system function (1) through replenishment of the naive T-cell pool and maintenance of diversity of the T-cell receptor repertoire, establishment of central immune tolerance by depleting selfreactive T-cell clones, and generation of natural regulatory T cells to maintain immune balance (2, 3). Many intrinsic and extrinsic factors can induce atrophy of the mature thymus and disrupt thymic functions (4, 5). Thymic atrophy is generally believed to result from deterioration of the interactions between lymphohematopoietic progenitor cells and nonhematopoietic thymic stromal cells (TSCs), 3 primarily thymic epithelial cells (TECs) in the thymus (6, 7). Therefore, changes in expression of genes and transcription factors, related to lymphohematopoietic progenitor cell and/or TEC functions may regulate thymic involution.FoxN1 is an epithelial cell-autonomous gene that encodes a forkhead-box transcription factor related to the immune system (8) and skin epithelial cells (9). FOXN1 in humans and FoxN1 in rodents are highly conserved in their sequence and function. A mutation in FoxN1 generates alymphoid cystic thymic dysgenesis due to defective TECs (10, 11), causing primary T-cell immunodeficiency (12-15), and leads to a hairless "nude" phenotype (9). TECs have two major subsets, medullary and cortical TECs (mTEC and cTEC), based on anatomic regions, expressed molecules, and function. mTECs mediate negative selection of T cells and control the maturation of T cells prior to leaving the thymus, whereas cTECs foster the development of CD4 Ϫ 8 Ϫ T-cell progenitors and regulate positive selection of T cells. Both mTECs and cTECs are FoxN1-dependent (16) during fetal thymic organogenesis, as demonstrated in mouse models (11,17,18). However, it is unclear whethe...

A highly sensitive analytical method for the simultaneous determination of 39 gaseous and particulate polycyclic aromatic hydrocarbons (PAHs) was used to determine the PAH composition of indoor and outdoor air in Shimizu, Japan. In both indoor and outdoor air, gaseous PAH concentrations were higher in summer than in winter, whereas particulate PAH concentrations were higher in winter than in summer. Correlation analysis indicated that indoor PAH compositions, especially the gaseous PAH composition, differed significantly from outdoor PAH compositions. Gaseous PAH concentrations indoors were significantly affected by insect repellents and heating sources. Particulate PAH concentrations indoors were significantly affected by cigarette smoking, the age and type (wood) of the house, and outdoor PAH concentrations. Inhalation risk associated with carcinogenic PAHs was estimated by using toxic equivalency factors based on the potency of benzo[a]pyrene (BaP). The carcinogenicity of the indoor PAH mixture was dominated by naphthalene followed by BaP and dibenz[a,h]anthracene.

The functions of a chemokine CXC chemokine ligand (CXCL) 12/stromal cell-derived factor-1/pre-B cell growth stimulating factor and its physiologic receptor CXCR4 in T cell development are controversial. In this study, we have genetically further characterized their roles in fetal and adult T cell development using mutant and chimeric mice. In CXCL12−/− or CXCR4−/− embryos on a C57BL/6 background, accumulation of T cell progenitors in the outer mesenchymal layer of the thymus anlage during initial colonization of the fetal thymus was comparable with that seen in wild-type embryos. However, the expansion of CD3−CD4−CD8− triple-negative T cell precursors at the CD44−CD25+ and CD44−CD25− stages, and CD4+CD8+ double-positive thymocytes was affected during embryogenesis in these mutants. In radiation chimeras competitively repopulated with CXCR4−/− fetal liver cells, the reduction in donor-derived thymocytes compared with wild-type chimeras was much more severe than the reduction in donor-derived myeloid lineage cells in bone marrow. Triple negative CD44+CD25+ T cell precursors exhibited survival response to CXCL12 in the presence of stem cell factor as well as migratory response to CXCL12. Thus, it may be that CXCL12 and CXCR4 are involved in the expansion of T cell precursors in both fetal and adult thymus in vivo. Finally, enforced expression of bcl-2 did not rescue impaired T cell development in CXCR4−/− embryos or impaired reconstitution of CXCR4−/− thymocytes in competitively repopulated mice, suggesting that defects in T cell development caused by CXCR4 mutation are not caused by reduced expression of bcl-2.