The formation of a barrier by tight junctions is important in epithelia of various tissues. Substance P (SP) and insulin-like growth factor (IGF)-1 synergistically promote barrier function in the corneal epithelium. We have now examined the effects of SP and IGF-1 on expression of the tight-junction protein zonula occludens (ZO)-1 in A431 human epidermoid carcinoma cells. Reverse transcription-polymerase chain reaction (RT-PCR) and immunoblot analyses revealed that SP and IGF-1 increased the amounts of ZO-1 mRNA and protein in these cells in a concentration-dependent manner, with neither SP nor IGF-1 alone having such an effect. The SP- and IGF-1-induced up-regulation of ZO-1 was accompanied by phosphorylation of extracellular signal-regulated kinase (ERK), and both of these effects were blocked by PD98059, an inhibitor of ERK activation. SP and IGF-1 also increased the transepithelial electrical resistance (TER) (an indicator of barrier function) of an A431 cell monolayer in a manner sensitive to PD98059. Our results thus suggest that the synergistic induction of ZO-1 expression by SP and IGF-1 may promote barrier function in skin epithelial cells.

A 19-year-old man with severe active ulcerative colitis was admitted to our hospital where he was prescribed 80 mg prednisolone and underwent leukocytapheresis (LCAP). Two weeks after initiating therapy, his symptoms had not recovered. We administered cyclosporin via continuous intravenous infusion for 12 days. Although his clinical symptoms improved, he complained of severe headache. Immediate plain computed tomography (CT) and magnetic resonance imaging angiography (MRA) revealed extensive thrombosis in the superior sagittal sinus and right transverse sinus. We treated this condition with the anticoagulant agent, heparin, which prevents and can treat venous thrombosis. We report an occurrence of cerebral sinus thrombosis accompanying ulcerative colitis, where active anticoagulant therapy was useful.

Citation: Morishige N, Murata S, Nakamura Y, et al. Coordinated regulation of palladin and a-smooth muscle actin by transforming growth factor-b in human corneal fibroblasts. Invest Ophthalmol Vis Sci. 2016;57:3360-3368. DOI:10.1167/iovs.15-18763 PURPOSE. To investigate the role of palladin in the cornea, we examined expression of this actin assembly-related protein in normal, diseased, or injured corneal tissue as well as in cultured corneal fibroblasts. METHODS.Expression of palladin and a-smooth muscle actin (a-SMA) in the rat cornea with an incision wound, in the normal and diseased human cornea, and in cultured human corneal fibroblasts was examined by immunofluorescence or immunoblot analysis.RESULTS. The expression of both palladin and a-SMA was detected at the lesion site during wound healing in the rat cornea. Whereas neither palladin nor a-SMA was detected in the normal human cornea, the colocalization of both proteins was detected in diseased human corneas with underlying conditions characterized by the presence of fibrosis. The expression of both palladin and a-SMA in cultured human corneal fibroblasts was increased by transforming growth factor-b (TGF-b) in a manner sensitive to inhibition by blockers of Smad or mitogen-activated protein kinase (MAPK) signaling. Finally, RNA interference-mediated depletion of palladin attenuated the TGF-b-induced upregulation of a-SMA expression in human corneal fibroblasts as well as TGF-b-induced collagen gel contraction mediated by these cells. CONCLUSIONS.Palladin is expressed in the rat and human cornea in association with scar formation. Expression of palladin in human corneal fibroblasts is increased by TGF-b in a manner dependent on Smad and MAPK signaling and is required for the TGF-b-induced upregulation of a-SMA.

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Reduktion der Lumazine (I) mit aktiviertem Aluminium in wäßrig‐methanolischem Ammoniak liefert unter Ringverengung die Theophylline (II).