Biomedical subjects

Takashi Amagai

Publications and source records attributed to Takashi Amagai.

At least 19 recordsLinked to original sources

PubMed2006

Expression of Dll4 and CCL25 in Foxn1-negative epithelial cells in the post-natal thymus.

Foxn1 transcription factor is known to be essential for development of the thymic organ. We analyzed whether Foxn1 expression in thymic epithelial cells is necessary for the expression of functional molecules such as Delta-like 4 (Dll4) and CCL25, and whether maintenance of these molecular expressions depends on the Foxn1 transcription factor. We show that almost all thymic epithelial cells in the early thymus anlagen express Foxn1, and Dll4 and CCL25 are limitedly expressed in Foxn1-positive epithelial cells. The results are consistent with previous reports suggesting the indispensability of Foxn1 for epithelial cell differentiation which enables these cells to induce the expressions of CCL25 (Bleul, C. C. and Boehm, T. 2000. Chemokines define distinct microenvironments in the developing thymus. Eur. J. Immunol. 30:3371), Dll1 and Dll4 (Tsukamoto, N., Itoi, M., Nishikawa, M. and Amagai, T. 2005. Lack of Delta like 1 and 4 expressions in nude thymus anlages. Cell. Immunol. 234:77). On the other hand, the expression of Foxn1 was not detectable in a large number of post-natal thymic epithelial cells. Both Foxn1-positive and -negative epithelial cells seem to express Dll4 and CCL25. Therefore, the expressions of Dll4 and CCL25 are independent of Foxn1 transcription factor in the post-natal thymus. These results indicate that in the post-natal thymus, epithelial cells may maintain the expressions of those functional molecules without the aid of Foxn1 transcription factor.

Animals↗

PubMed2006

Seasonal and spatial trends of suspended-particle associated polycyclic aromatic hydrocarbons in urban Shizuoka, Japan.

We characterized the monthly variations of 21 polycyclic aromatic hydrocarbons (PAHs) associated with suspended particles in the city of Shizuoka, Japan, over 12 months during 2001 and 2002. The fraction of fine particles (less than 2.5 microm diameter (PM2.5)) ranged from 40 to 60% of total suspended particles over the 12 months of the study, and their concentrations ranged from 19.3 to 41.7 microg/m(3). Almost all the PAHs were found in the PM2.5 fraction, in which the summed concentration (sigma PAH) of the 21 PAHs ranged from 1.0 to 8.4 ng/m(3). PAH concentrations were elevated in the colder seasons, but the concentrations of the PM2.5 fraction of suspended particles were not. The composition of PAHs associated with PM2.5 changed little during the year of our study, indicating that seasonal sources such as heating have little effect. Factor analysis showed that three factors explain little of the seasonal variations in the sources of PAHs. Contour maps showed high concentrations of indicator PAHs for gasoline and diesel engine sources distributed along major roads and near factories on the outskirts of the city. We concluded that the contribution of vehicle exhausts to particle-associated PAHs is significant not only in the central city, but also in outer areas associated with major ring roads, and suggest that air pollution in outskirts of urban area also is concerned for health risk associated with the exposure.

Air Pollutants↗

PubMed2006

Simultaneous determination of gaseous and particulate chlorinated polycyclic aromatic hydrocarbons in emissions from the scorching of polyvinylidene chloride film.

An analytical method for the determination of gaseous and particulate chlorinated polycyclic aromatic hydrocarbons (ClPAHs) was investigated. By means of this method, concentrations and isomer profiles of the 27 target ClPAHs could be analyzed. To evaluate the usefulness of the method for analyzing ClPAH emissions, laboratory-scale scorching tests were performed on polyvinylidene chloride (PVDC) plastic wrap over a flame of the gas burner. Only seven of the target ClPAHs were detected, and all compounds detected had 2, 3, or 4 rings. The detected ClPAHs were present in both the particulate phase and the gaseous phase, but they were present at higher concentrations in the gaseous phase than in the particulate phase. Relationships between the number of chlorine substituents on the naphthalene/phenanthrene rings and the overall concentration and the percentage in the particulate phase were also investigated.

Air Pollutants↗

PubMed2006

Temporal trends and relationships of particulate chlorinated polycyclic aromatic hydrocarbons and their parent compounds in urban air.

Concentrations of 12 chlorinated polycyclic aromatic hydrocarbons (CIPAHs) and the corresponding 5 parent PAHs associated with particulates in urban air in Shizuoka, Japan, were investigated from 1992 to 2002. Among the seven target CIPAHs that were detected in the air samples, 6-chlorobenzo[a]pyrene (6-ClBaP) had the highest mean concentration (15 pg m(-3)), followed by 1-chloropyrene (5.2 pg m(-3)) and 7-chlorobenz[a]anthracene (3.1 pg m(-3)). The concentrations of all the ClPAHs and PAHs, except 6-ClBaP, were higher in winter than in summer. Over the study period, the concentrations of the CIPAHs, except 6-ClBaP, remained almost constant, whereas the parent PAH concentrations declined moderately. There was significant correlation between the concentrations of the ClPAHs (except 3,9- and 9,10-dichlorophenanthrene) and the concentrations of the corresponding parent PAHs. Compositional analysis showed that the proportions of the detected PAHs generally did not vary over the period, whereas the proportion of 6-ClBaP relative to the total ClPAH concentration decreased over time. Comparison of the concentration profile of certain ClPAHs normalized to the concentration of 3-chlorofluoranthene, which is relatively photostable, with the profile for a traffic air sample reported previously revealed that there was no similarity between the two profiles. Factor analysis indicated that the atmospheric behavior of the ClPAHs, except for 6-ClBaP, may be similar to that of the parent PAHs, and that the atmospheric behavior of 6-ClBaP may differ from that of the other ClPAHs. The factor analysis also suggested that the emission sources for the ClPAHs (except for 6-CIBaP) may be similar to the sources of the parent PAHs.

Air↗

PubMed2006

Evidence for a functional second thymus in mice.

The thymus organ supports the development of T cells and is located in the thorax. Here, we report the existence of a second thymus in the mouse neck, which develops after birth and grows to the size of a small lymph node. The cervical thymus had a typical medulla-cortex structure, was found to support T cell development, and could correct T cell deficiency in athymic nude mice upon transplantation. The identification of a regular second thymus in the mouse may provide evolutionary links to thymus organogenesis in other vertebrates and suggests a need to reconsider the effect of thoracic thymectomy on de novo T cell production.

Animals↗

PubMed2005

Organic air pollutants inside and outside residences in Shimizu, Japan: levels, sources and risks.

Concentrations of 38 organic air pollutants including aromatic hydrocarbons (AHCs), carbonyl compounds (CCs), volatile organic halogenated compounds (VOHCs), and organophosphorus compounds (OPCs) were measured in indoor and outdoor air in an industrial city, Shimizu, Shizuoka Prefecture, Japan. Levels of pollutants tended to be higher indoors than outdoors in both summer and winter except for benzene, carbon tetrachloride, trichloroethylene, tetrachloroethylene, and dichlorvos (DDVP). This trend was especially pronounced for CCs such as formaldehyde and acetaldehyde. For the organic air pollutants, the concentrations of AHCs and VOHCs substantially increased in winter, but not those of CCs and OPCs; the trends were similar for both indoors and outdoors. We investigated possible indoor sources of pollutants statistically. Multiple regression analysis of corresponding indoor and outdoor concentrations and the responses to our questionnaire showed that indoor concentrations of certain AHCs were significantly affected by their outdoor concentrations and cigarette smoking. For formaldehyde, indoor concentrations were significantly affected by house age and the presence of carpet or pets. For p-dichlorobenzene (pDCB), the concentrations in bedroom trended to be higher than those in other indoors and outdoors, suggested that mothballs for clothes present in bedrooms are the principal indoor source of pDCB. We compared indoor and outdoor pollutant concentrations to acceptable risk limits for 11 organic air pollutants. In indoors without smoking samples, the geometric mean concentrations of benzene, formaldehyde, acetaldehyde, carbon tetrachloride, pDCB, and DDVP exceeded the equivalent concentration representing the upper bound of one-in-one-hundred-thousand (1x10(-5)) excess risk over a lifetime of exposure.

Air Pollutants↗

PubMed2005

Prediction of personal exposure to PM2.5 and carcinogenic polycyclic aromatic hydrocarbons by their concentrations in residential microenvironments.

We measured exposure to fine particles (PM2.5) and polycyclic aromatic hydrocarbons (PAHs), including carcinogenic PAHs, in multiple locations for a diverse population of participants who resided in Shizuoka, Japan. In summer and winter 2002 we surveyed personal concentrations, those of four primary indoor microenvironments-living room, bedroom, kitchen (summer only), and workplace--and those outside the subjects' houses. Concentrations of PM2.5 and PAHs tended to be higher during winter. Median PM2.5 concentration was highest in living room samples during winter but in personal samples during summer. The median PAH concentrations normalized to the cancer potency equivalence factor of benzo[a]pyrene (BaP-TEQ) was highest in the bedroom during winter but outdoors in summer. Personal exposure level profiles differed markedly between smokers and nonsmokers. Personal exposures to BaP ([BaP]p) and BaP-TEQ ([BaP-TEQ]P) in nonsmokers were strongly correlated. Personal exposures of nonsmokers, as calculated from the corresponding time-weighted indoor and outdoor concentrations, were consistent with measured levels of BaP but not PM2.5. Personal exposure of nonsmokers to BaP, as calculated from the time-weighted living room, bedroom, and either workplace or outdoor concentrations, accounted for 92-107% of the measured levels of BaP-TEQ.

Air Pollution, Indoor↗

PubMed2005

Polycomb group gene mel-18 regulates early T progenitor expansion by maintaining the expression of Hes-1, a target of the Notch pathway.

Polycomb group (PcG) proteins play a role in the maintenance of cellular identity throughout many rounds of cell division through the regulation of gene expression. In this report we demonstrate that the loss of the PcG gene mel-18 impairs the expansion of the most immature T progenitor cells at a stage before the rearrangement of the TCR beta-chain gene in vivo and in vitro. This impairment of these T progenitors appears to be associated with increased susceptibility to cell death. We also show that the expression of Hes-1, one of the target genes of the Notch signaling pathway, is drastically down-regulated in early T progenitors isolated from mel-18(-/-) mice. In addition, mel-18(-/-) T precursors could not maintain the Hes-1 expression induced by Delta-like-1 in monolayer culture. Collectively, these data indicate that mel-18 contributes to the maintenance of the active state of the Hes-1 gene as a cellular memory system, thereby supporting the expansion of early T progenitors.

Animals↗

PubMed2005

Thymic anlage is colonized by progenitors restricted to T, NK, and dendritic cell lineages.

It remains controversial whether the thymus-colonizing progenitors are committed to the T cell lineage. A major problem that has impeded the characterization of thymic immigrants has been that the earliest intrathymic progenitors thus far identified do not necessarily represent the genuine thymic immigrants, because their developmental potential should have been influenced by contact with the thymic microenvironment. In the present study, we examined the developmental potential of the ontogenically earliest thymic progenitors of day 11 murine fetus. These cells reside in the surrounding mesenchymal region and have not encountered thymic epithelial components. Flow cytometric and immunohistochemical analyses demonstrated that these cells are exclusively Lin(-)c-kit(+)IL-7R(+). Limiting dilution analyses disclosed that the progenitors with T cell potential were abundant, while those with B cell potential were virtually absent in the region of day 11 thymic anlage. Clonal analyses reveled that they are restricted to T, NK, and dendritic cell lineages. Each progenitor was capable of forming a large number of precursors that may clonally accommodate highly diverse TCRbeta chains. These results provide direct evidence that the progenitors restricted to the T/NK/dendritic cell lineage selectively immigrate into the thymus.

Animals↗

PubMed2005

Occurrence, profiles, and photostabilities of chlorinated polycyclic aromatic hydrocarbons associated with particulates in urban air.

The atmospheric levels of 12 chlorinated polycyclic aromatic hydrocarbons (ClPAHs) associated with particulates at an urban site in Japan were investigated. Only 7 of the 12 species studied were detected in air samples collected monthly during 2002. 1-Chloropyrene (1-ClPy) was detected at the highest concentration (7.5 pg m(-3) (annual mean)), followed by 6-chlorobenzo[a]pyrene (6-ClBaP; 5.6 pg m(-3)) and 9,10-dichlorophenanthrene (5.1 pg m(-3)). The concentrations of the ClPAHs tended to be higher in winter than in summer, with the exception of the 6-ClBaP concentration, which was high in both summer and winter. Correlation analysis also indicated that the behavior of 6-CIBaP differed significantly from that of the other ClPAHs. Comparison of the atmospheric ClPAH concentration profile normalized to 1-CIPy concentration with that for a traffic air sample revealed significant differences between the profiles. The behavior of the atmospheric ClPAHs was also influenced by the origin of the associated particulates, which varied according to season. The positions of chlorination in the detected ClPAHs were consistent with those where the frontier electron density was high. This means that the atmospheric ClPAHs were formed by secondary reactions with chlorine atoms. The photostabilities of the ClPAHs were also investigated in laboratory experiments using a chemical model system. The ClPAHs decayed according to first-order reaction rate kinetics, with photostabilities increasing in the order 6-ClBaP < 1-ClPy < 7-ClBaA < ClPhe < ClFluor, consistent with the trend for the parent PAHs. The photolyses of chlorophenanthrenes and 7-chlorobenz[a]anthracene were confirmed to proceed by initial abstraction of chlorine, followed by oxidative degradation.

Air Pollutants↗

PubMed2005

Lack of Delta like 1 and 4 expressions in nude thymus anlages.

Notch signaling is required for the early steps in T cell development. However, distribution of Notch ligands in the thymus anlages is not clear. We investigated the expressions of Delta like (Dll) 1 and Dll4 in the mouse thymus anlages. In the normal thymus anlages on embryonic day 13, Dll4 is strongly expressed throughout the epithelial region, but Dll1 is expressed only in scattered cells. In contrast, epithelial cells of the nude thymus anlages express neither Dll1 nor Dll4. These results indicate that expressions of Dll1 and Dll4 in thymic epithelial cells are regulated by Foxn1 transcriptional factor.

Animals↗

PubMed2004

Polycyclic aromatic hydrocarbons in indoor and outdoor environments and factors affecting their concentrations.

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.

Air Pollutants↗

PubMed2004

Spatial distributions and profiles of atmospheric polycyclic aromatic hydrocarbons in two industrial cities in Japan.

The spatial distribution and concentration profiles of 39 vapor and particulate polycyclic aromatic hydrocarbons (PAHs) have been investigated in two Japanese industrial cities (Fuji and Shimizu; a summer and winter season in each). The concentrations of particulate PAHs in winter tended to be higher than those in the summer, but for vapor PAHs, this was not the case. Significant correlations (p < 0.01) were found between most of the PAH concentrations monitored in winter, suggesting the presence of common emission sources. To identify PAH spatial distributions and emission sources in the area, we created contour maps for PAHs monitored; this indicates that the distinctive local distributions correspond to the emission sources. PAH profiles based on benzo[e]pyrene (BeP) concentration, especially for certain relatively heavy molecular weight PAHs, showed differential behaviors among divided areas related to potential regional emission sources such as paper-making plants, power plants, and traffic. We conclude that the origins of atmospheric PAHs in the surveyed areas were dominated by not only traffic but also by stationary emission sources such as paper-making plants and power plants and that local distributions were dependent on the local wind direction.

Air Movements↗

PubMed2004

Seasonal variability of 1-chloropyrene on atmospheric particles and photostability in toluene.

The occurrence of a mutagenic compound, 1-chloropyrene (Cl-Py), in extracts of ambient particulate matter at an urban site in Japan has been investigated. Samples were collected with a high-volume air sampler for 24 h periods over the course of 1 week in winter (February), spring (May), summer (August), and autumn (November) 2002. The Cl-Py levels showed seasonal variation, ranging from 2.4 pg/m(3) (summer) to 18.9 pg/m(3) (winter). This variation would indicate that the lower temperatures in winter results in an increased distribution of Cl-Py from vapor phase to the particle phase. In addition, there is also the possibility that ambient Cl-Py is emitted from seasonal sources or is susceptible to photodegradation by sunlight, or both. The photodegradation of Cl-Py in a laboratory experiment was conducted to simulate the compound's fate on airborne particle surfaces. The degradation of Cl-Py proceeded by a first-order reaction with a rate constant of 0.72 h(-1). In the presence of a radical sensitizer, 9,10-anthraquinone (AQ), the photodegradation rate of Cl-Py was elevated in comparison with the rate in the absence of AQ. In addition, the dechlorination of Cl-Py (i.e., the formation of Py) occurred in the presence of AQ.

Air Pollutants↗

PubMed2003

A role of CXC chemokine ligand 12/stromal cell-derived factor-1/pre-B cell growth stimulating factor and its receptor CXCR4 in fetal and adult T cell development in vivo.

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.

Aging↗

PubMed2003

Development of thymic microenvironments in vitro is oxygen-dependent and requires permanent presence of T-cell progenitors.

Development of a mature T-cell repertoire in the thymus depends on lympho-stromal interaction between thymocytes and stromal cells. To facilitate intercellular contact, the epithelium in the thymus has differentiated into a unique three-dimensionally (3D)-oriented network. Here we analyze factors influencing induction and maintenance of the 3D configuration of the epithelial network in fetal thymic lobes in vitro. We show that the 3D configuration of the thymic stroma depends on (a) the oxygen pressure in vitro and (b) permanent physical contact between stromal cells and developing thymocytes. This latter feature is demonstrated by incubation of fetal thymic lobes with deoxyguanosine (d-Guo), inducing a 2D-organized thymic stroma, with thymic cysts appearing. Reconstitution of d-Guo-treated lobes with a limited number of flow-sorted T-cell progenitors restores the 3D configuration of the thymic epithelium, but only at high oxygen pressure. This study underlines the plasticity of thymic epithelium and shows that the unique organization of the thymic epithelium is dependent on both oxygen and crosstalk signals derived from developing thymocytes.

Animals↗

PubMedDate not supplied

The 1997 haze disaster in Indonesia: its air quality and health effects.

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.

Adult↗

PubMedDate not supplied

Simultaneous liquid chromatographic determination of 39 polycyclic aromatic hydrocarbons in indoor and outdoor air and application to a survey on indoor air pollution in Fuji, Japan.

An analytical method was established for the simultaneous determination of 39 polycyclic aromatic hydrocarbons (PAHs) in air. The method was applied to a survey of gaseous and particulate PAHs in household indoor air. The survey was performed in 21 houses in the summer of 1999 and in 20 houses in the winter of 1999-2000 in Fuji, Japan. Thirty-eight PAHs were determined in indoor and outdoor air in the summer, and 39 PAHs were determined in indoor and outdoor air in the winter. The concentrations of gaseous PAHs in indoor air tended to be higher than those in outdoor air in the summer and winter. The concentrations of particulate PAHs in indoor air were the same as or lower than those in outdoor air in the summer and winter. PAH profiles, correlations between PAH concentrations, and multiple regression analysis were used to determine the factors affecting the indoor PAH concentrations. These results showed that gaseous PAHs in indoor air were primarily from indoor emission sources, especially during the summer, and that indoor particulate PAH concentrations were significantly influenced by outdoor air pollution.

Air Pollutants, Occupational↗