Possible mechanisms of the crosstalk between Langerhans cells and regulatory T cells in extramammary Paget disease by receptor activator of nuclear factor kappa B (RANK) ligand/RANK pathways.

BACKGROUND: Extramammary Paget disease (EMPD) is a skin adenocarcinoma of apocrine gland origin, in which Paget cells express receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) and matrix metalloproteinase (MMP)-7, and release soluble (s)RANKL into the tumour microenvironment. We previously reported that about 60% of the RANK+ cells among the stromal cells are M2 macrophages, but the identity of the remaining population of RANK+ cells is still unknown. OBJECTIVES: To investigate the unknown subpopulation of RANK-expressing cells in EMPD. METHODS: The main population of RANK-expressing cells in the epidermis was composed of epidermal Langerhans cells (LCs). To explore the effects of RANKL on LCs, we stimulated LCs generated from human CD34+ hematopoietic progenitor cells with graded concentrations of sRANKL. To further examine the correlation between LCs and regulatory T cells (Tregs) in EMPD, we employed immunohistochemical staining. RESULTS: sRANKL stimulation was shown to augment the production of C-C motif chemokine ligand 17 (CCL17) from LCs. We additionally demonstrated CCL17 expression by CD1a+ LCs in EMPD in an immunofluorescence study. Spearman's rank correlation test confirmed a correlation between the number of LCs and the number of Foxp3+ Tregs in the lesional skin of invasive EMPD. In addition, the numbers of Foxp3+ Tregs in the sentinel lymph nodes of metastatic EMPD were significantly higher than those of metastatic melanoma, which did not express RANKL. CONCLUSIONS: The findings suggest that the RANKL/RANK pathway in EMPD might contribute to the recruitment of Tregs and to maintenance of the tumour microenvironment.

Enhanced silicon oxidation on titanium-covered Si(001).

We report on a core level photoemission study of the formation of an ultrathin SiO(x) layer grown at the interface of a titanium-covered Si(001) surface. Oxygen exposure at room temperature induces a large chemical shift of the Si 2p state, predominantly assigned to Si(4+). The results indicate that a SiO(2 - δ) layer, close to the stoichiometry of SiO(2), is formed below the TiO(x) film. The thickness of the SiO(2 - δ) layer is estimated to be ∼ 0.9 nm, corresponding to three to four oxide layers. Further chemical shift caused by annealing is attributed to the formation of titanium silicate (TiSi(x)O(y)).

Final state interaction observed in M(2,3)VV Auger profile of Cu(110).

We have measured the M(2,3)VV Auger spectra of Cu(110) and studied the final state interaction following the Cu 3p core electron excitation. We have observed that the kinetic energy of the M(2,3)VV Auger electron shifts to an energy higher than that of the normal Auger electrons near the Cu 3p threshold, and it converges to the constant kinetic energy of the normal Auger electrons as the excitation energy increases above the Cu 3p threshold. In the excitation energy dependence of the kinetic energies of the M(2,3)VV Auger electrons, we observed step features at the excitation energies corresponding to the 3p core electron excitations to the L(1) and X(1) van Hove singularities in the valence states. The kinetic energy shifts of the M(2,3)VV Auger electrons are reasonably understood by considering the localization of the two-hole Auger final state and the hybridization between Cu 3d states and other valence states.

Effects of ginseng saponins on responses induced by various receptor stimuli.

We investigated the effects of four ginseng saponins, ginsenoside-Rb1, -Rg2, -Rg3 and -Ro, on the responses induced by receptor stimulation of various stimuli. Ginsenoside-Rg2 (1-100 microM) reduced the secretions of catecholamines from bovine adrenal chromaffin cells stimulated by acetylcholine and gamma-aminobutyric acid but not by angiotensin II, bradykinin, histamine and neurotensin. In guinea-pig, the ginsenoside also diminished the nicotine-induced secretion of catecholamines from the adrenal chromaffin cells, but it did not affect the muscarine- and the histamine-induced ileum contractions. On the other hand, ginsenoside-Rg3 (1-100 microM) reduced not only the acetylcholine-, the gamma-aminobutyric acid- and the neurotensin-induced secretions but also, at a higher concentration (100 microM), the angiotensin II-, the bradykinin- and the histamine-induced secretions from the bovine chromaffin cells. Furthermore, the saponin (3-100 microM) significantly inhibited the muscarine- and the histamine-induced ileum contractions of the guinea-pig. Ginsenoside-Rb1 and -Ro had no marked effect on their responses. These results strongly suggest that ginsenoside-Rg2 is a potent selective blocker of nicotinic acetylcholine and gamma-aminobutyric acid receptors (ionotropic receptors) and ginsenoside-Rg3 is not only a blocker of ionotropic receptors but also an antagonist of muscarinic or histamine receptors.

A new compact spin- and angle-resolving photoelectron spectrometer with a high efficiency.

A portable spin- and angle-resolving photoelectron spectrometer has been constructed, equipped with a newly developed compact retarding-potential Mott-scattering electron spin polarimeter with an efficiency of 1.9 x 10(-4) for a gold target. Based on Monte Carlo calculations for the spin-dependent electron-scattering process and electron ray-tracing calculations, a novel design of the retarding-field electron optics with 0.59 sr collection solid angle for scattered electrons has been accomplished. Utilizing this spectrometer, the spin- and angle-resolved photoelectron spectra have been measured and the spin-dependent electronic structure of Ni(110), Ni(110)-p(2 x 1)O and Ni(110)-c(2 x 2)S along the ${\overline {\Gamma S}}$ line of the Ni(110) surface Brillouin zone have been studied.