No abstract

The liverwort Radula perrottetii contains various bibenzyl derivatives which are known to possess various biological activities, such as anti-inflammatory effects. Mast cells (MC) play crucial roles in allergic and inflammatory diseases; thus, inhibition of MC activation is pivotal for the treatment of allergic and inflammatory disorders. We investigated the effects of perrottetin D (perD), isolated from Radula perrottetii, and perD diacetate (Ac-perD) on antigen-induced activation of MCs. Bone marrow–derived MCs (BMMCs) were generated from C57BL/6 mice. The degranulation ratio, histamine release, and the interleukin (IL)-4 and leukotriene B4 productions on antigen-triggered BMMC were investigated. Additionally, the effects of the bibenzyls on binding of IgE to FcεRI were observed by flow cytometry, and signal transduction proteins was examined by Western blot. Furthermore, binding of the bibenzyls to the Fyn kinase domain was calculated. At 10 μM, perD decreased the degranulation ratio (p<0.01), whereas 10 μM Ac-perD down-regulated IL-4 production (p<0.05) in addition to decreasing the degranulation ratio (p<0.01). Both compounds tended to decrease histamine release at a concentration of 10 μM. Although 10 μM perD reduced only Syk phosphorylation, 10 μM Ac-perD diminished phosphorylation of Syk, Gab2, PLC-γ, and p38. PerD appeared to selectively bind Fyn, whereas Ac-perD appeared to act as a weak but broad-spectrum inhibitor of kinases, including Fyn. In conclusion, perD and Ac-perD suppressed the phosphorylation of signal transduction molecules downstream of the FcεRI and consequently inhibited degranulation, and/or IL-4 production. These may be beneficial potential lead compounds for the development of novel anti-allergic and anti-inflammatory drugs.

A new two–dimensional process simulator HITOP is developed which can handle oxidation, diffusion, and ion implementation processes. This simulator can be used for process design of practical scaled MOS basic circuits and has the following characteristics: (i) the region of a size from a few μm to a few tens μm containing multiple MOS devices can be simulated simultaneously; (ii) the variation of the layered film formation during the process can be recognized; (iii) a highly accurate simulation is possible from the viewpoint of physical chemistry modeling and of numerical algorithms; (iv) a bidirectional interface with the shape simulator is contained. It is possible to accept the shape of the etching and deposition processes, continue execution, and return the shape data after the process to the shape simulator. For the benefit of the user, changes of the shape of the junction during the process, situation of the growth of the oxide film and the modification of the top layer are displayed successively so that the basic information for circuit design is provided. The present system can be used with a layout processor and a device simulator.