Interferon-gamma-inducing factor/interleukin-18 is a novel cytokine that reportedly augments natural killer (NK) activity in human and mouse peripheral blood mononuclear cell cultures in vitro and has recently been designated IL-18. In this study, IL-18 exhibited significant antitumor effects in BALB/c mice challenged intraperitoneally (i.p.) with syngeneic Meth A sarcoma when administered i.p. on days 1, 2 and 3 after challenge. Intravenous (i.v.) administration also induced antitumor effects in the tumor-bearing mice; however, subcutaneous (s.c.) administration did not. When mice were twice pretreated with 1 microg IL-18 3 days and 6 h before tumor challenge, all mice survived whereas control mice died within 3 weeks of challenge. Inhibitory effects on Meth A cell growth in vitro were not observed with either IL-18 or interferon gamma. The effects of IL-18 pretreatment were abrogated by abolition of NK activity after mice had been injected with anti-asialo GM1 antibody 48 h before and, 24 h and 72 h after tumor challenge. Mice pretreated with IL-18 and surviving tumor challenge resisted rechallenge with Meth A cells but could not reject Ehrlich ascites carcinoma, and spleen cells from the resistant mice, but not control mice, exhibited cytotoxic activity against Meth A cells in vitro after restimulation with mitomycin C-treated Meth A cells for 5 days. The effector cells in the spleen cell preparations from resistant mice appear to be CD4+ cells because cytolytic activity was significantly inhibited after depletion of this subset by monoclonal antibodies and complement. In conclusion, IL-18 exhibits in vivo immunologically (primarily NK) mediated antitumor effects in mice challenged with syngeneic Meth A sarcoma and induces immunological memory and the generation of cytotoxic CD4+ cells.
A lack of sources makes it difficult to discover the personhood of premodern Japanese royal women-how they viewed themselves or wanted to be viewed by others. Hachijō-in (1137Hachijō-in ( -1211, a royal heiress, strove to protect her lineage, which had begun to weaken in the political and military turmoil of the late twelfth century. Through a close analysis of her prayer of dedication (kōmon), this article explores how she reflected upon herself after undergoing a time of great difficulty as an unmarried royal daughter. In contrast to the historical overviews that typically emphasise the roles of medieval male royals and warriors, this study demonstrates that royal daughters also played significant religio-political roles. They developed a strong sense of responsibility for supporting royal authority and commemorating deceased family members. Hachijō-in's prayer reveals her objectives, feelings and values as a woman through a deliberate construction of herself in front of the Great Bodhisattva Hachiman of Iwashimizu Shrine.Although the Heian period (794-1185) is famous as a time when premodern Japanese female courtiers produced many poems, memoirs and tales, few of their female patrons-wives and daughters of the monarch-created
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