78 research outputs found
石田梅岩(石門心学)の『都鄙問答』にみる経営理念について
Ⅰ. はじめに Ⅱ. 石田梅岩の略歴と人物 Ⅲ. 石田梅岩の著述と『都鄙問答』について Ⅳ. 石門心学について V. 代表的著述『都鄙問答』にみる経営理念とその現代的意味 Ⅵ. おわり
Epithelial Cell Stretching and Luminal Acidification Lead to a Retarded Development of Stria Vascularis and Deafness in Mice Lacking Pendrin
Loss-of-function mutations of SLC26A4/pendrin are among the most prevalent causes of deafness. Deafness and vestibular dysfunction in the corresponding mouse model, Slc26a4−/−, are associated with an enlargement and acidification of the membranous labyrinth. Here we relate the onset of expression of the HCO3− transporter pendrin to the luminal pH and to enlargement-associated epithelial cell stretching. We determined expression with immunocytochemistry, cell stretching by digital morphometry and pH with double-barreled ion-selective electrodes. Pendrin was first expressed in the endolymphatic sac at embryonic day (E) 11.5, in the cochlear hook-region at E13.5, in the utricle and saccule at E14.5, in ampullae at E16.5, and in the upper turn of the cochlea at E17.5. Epithelial cell stretching in Slc26a4−/− mice began at E14.5. pH changes occurred first in the cochlea at E15.5 and in the endolymphatic sac at E17.5. At postnatal day 2, stria vascularis, outer sulcus and Reissner's membrane epithelial cells, and utricular and saccular transitional cells were stretched, whereas sensory cells in the cochlea, utricle and saccule did not differ between Slc26a4+/− and Slc26a4−/− mice. Structural development of stria vascularis, including vascularization, was retarded in Slc26a4−/− mice. In conclusion, the data demonstrate that the enlargement and stretching of non-sensory epithelial cells precedes luminal acidification in the cochlea and the endolymphatic sac. Stretching and luminal acidification may alter cell-to-cell communication and lead to the observed retarded development of stria vascularis, which may be an important step on the path to deafness in Slc26a4−/− mice, and possibly in humans, lacking functional pendrin expression
Lipid Motif of a Bacterial Antigen Mediates Immune Responses via TLR2 Signaling
The cross-talk between the innate and the adaptive immune system is facilitated
by the initial interaction of antigen with dendritic cells. As DCs express a
large array of TLRs, evidence has accumulated that engagement of these molecules
contributes to the activation of adaptive immunity. We have evaluated the
immunostimulatory role of the highly-conserved outer membrane lipoprotein P6
from non-typeable Haemophilus influenzae (NTHI) to determine
whether the presence of the lipid motif plays a critical role on its
immunogenicity. We undertook a systematic analysis of the role that the lipid
motif plays in the activation of DCs and the subsequent stimulation of
antigen-specific T and B cells. To facilitate our studies, recombinant P6
protein that lacked the lipid motif was generated. Mice immunized with
non-lipidated rP6 were unable to elicit high titers of anti-P6 Ig. Expression of
the lipid motif on P6 was also required for proliferation and cytokine secretion
by antigen-specific T cells. Upregulation of T cell costimulatory molecules was
abrogated in DCs exposed to non-lipidated rP6 and in
TLR2−/− DCs exposed to native P6, thereby resulting
in diminished adaptive immune responses. Absence of either the lipid motif on
the antigen or TLR2 expression resulted in diminished cytokine production from
stimulated DCs. Collectively; our data suggest that the lipid motif of the
lipoprotein antigen is essential for triggering TLR2 signaling and effective
stimulation of APCs. Our studies establish the pivotal role of a bacterial lipid
motif on activating both innate and adaptive immune responses to an otherwise
poorly immunogenic protein antigen
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