Mice deficient in lymphotoxin β receptor (LTβR) or interleukin 7 receptor α (IL-7Rα) lack Peyer's patches (PPs). Deficiency in CXC chemokine receptor 5 (CXCR5) also severely affects the development of PPs. A molecular network involving these three signaling pathways has been implicated in PP organogenesis, but it remains unclear how they are connected during this process. We have shown that PP organogenesis is initiated at sites containing IL-7Rα+ lymphoid cells and vascular cell adhesion molecule (VCAM)-1/intercellular adhesion molecule (ICAM)-1 expressing nonlymphoid elements. Here we characterize these lymphoid and nonlymphoid components in terms of chemokine signals. The lymphoid population expresses CXCR5 and has a strong chemotactic response to B lymphocyte chemoattractant (BLC). Importantly, chemokines produced by VCAM-1+ICAM-1+ nonlymphoid cells mediate the recruitment of lymphoid cells. Furthermore, we show that these VCAM-1+ICAM-1+ cells are mesenchymal cells that are activated by lymphoid cells through the LTβR to express adhesion molecules and chemokines. Thus, promotion of PP development relies on mutual interaction between mesenchymal and lymphoid cells.
The present study analyzed morphological and immunohistochemical changes of thymic epithelial cells in the irradiated and recovering rat thymus. Observations showed the number of thymocytes was initially severely reduced after irradiation but abruptly increased on days 3 to 5 after 6 Gy and on days 7 to 11 after 8 Gy irradiation. To analyse the mechanisms for this abrupt recovery of the thymocytes after irradiation, the expression of p63 in the normal and irradiated thymus was immunohistochemically studied as the expression of this antigen may be related to the proliferation of epithelial cells. In the fetal thymus tissue, thymic epithelial cells were the principal cell type that stained strongly positive for p63. The sporadic expression of p63 was also observed in the normal adult thymus tissue, especially in the subcapsular region. An increased number of p63- positive cells in the thymus after irradiation indicates that repair or renewal of the thymic epithelial cells may be taking place because p63 is more specific to transient amplifying thymic epithelial cells. A RT-PCR analysis of p63 expression in irradiated and regenerating thymus tissue also showed an increased expression of p63 after irradiation compared with that of the normal thymus. These results suggest that changes in the thymic microenvironment-especially in relation to the repair and renewal of thymic epithelial cells- may have an important influence on thymocyte proliferation in the normal thymus as well as in the irradiated and recovering thymus.
Hyperlipidemia is a risk factor for abnormal cerebrovascular events. Rafts are cholesterol-enriched membrane microdomains that influence signal transduction. We previously showed that Rho-kinase-mediated Ca 2+ sensitization of vascular smooth muscle (VSM) induced by sphingosylphosphorylcholine (SPC) has a pivotal role in cerebral vasospasm. The goals of the study were to show SPC-Rho-kinase-mediated VSM contraction in vivo and to link this effect to cholesterol and rafts. The SPC-induced VSM contraction measured using a cranial window model was reversed by Y-27632, a Rho-kinase inhibitor, in rats fed a control diet. The extent of SPC-induced contraction correlated with serum total cholesterol. Total cholesterol levels in the internal carotid artery (ICA) were significantly higher in rats fed a cholesterol diet compared with a control diet or a β-cyclodextrin diet, which depletes VSM cholesterol. Western blotting and real-time PCR revealed increases in flotillin-1, a raft marker, and flotillin-1 mRNA in the ICA in rats fed a cholesterol diet, but not in rats fed the β-cyclodextrin diet. Depletion of cholesterol decreased rafts in VSM cells, and prevention of an increase in cholesterol by β-cyclodextrin inhibited SPC-induced contraction in a cranial window model. These results indicate that cholesterol potentiates SPC-Rho-kinase-mediated contractions of importance in cerebral vasospasm and are compatible with a role for rafts in this process.
Electron spin resonance (ESR) spectra have been measured in X-ray-irradiated CdS doped glass as functions of X-ray dose and effective X-ray energy. The intensity of the ESR signal is proportional to X-ray dose up to 40Gy. CdS-doped glass is more sensitive than a commercial alanine dosimeter. The intensity of the ESR signal decreases with decreasing effective X-ray energy for energies lower than 33 keV. Thermal stability was also studied.The ESR signal is relatively stable at room temperature. *
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