Leukocytosis in tobacco smokers has been well recognized; however, the exact cause has not been elucidated. To test the hypothesis that tobacco nicotine stimulates neutrophils in the respiratory tract to produce IL-8, which causes neutrophilia in vivo, we examined whether nicotine induces neutrophil-IL-8 production in vitro; the causative role of NF-kappaB in its production, in association with the possible production of reactive oxygen intermediates that activate NF-kappaB; and the nicotinic acetylcholine receptors (nAChRs) involved in IL-8 production. Nicotine stimulated neutrophils to produce IL-8 in both time- and concentration-dependent manners with a 50% effective concentration of 1.89 mM. A degradation of IkappaB-alpha/beta proteins and an activity of NF-kappaB p65 and p50 were enhanced following nicotine treatment. The synthesis of superoxide and the oxidation of dihydrorhodamine 123 (DHR) were also enhanced. The NOS inhibitor, nomega-Nitro-l-arginine methyl ester, prevented nicotine-induced IL-8 production, with an entire abrogation of DHR oxidation, IkappaB degradation, and NF-kappaB activity. Neutrophils spontaneously produced NO whose production was not increased, but rather decreased by nicotine stimulation, suggesting that superoxide, produced by nicotine, generates peroxynitrite by reacting with preformed NO, which enhances the NF-kappaB activity, thereby producing IL-8. The nAChRs seemed to be involved in IL-8 production. In smokers, blood IL-8 levels were significantly higher than those in nonsmokers. In conclusion, nicotine stimulates neutrophil-IL-8 production via nAChR by generating peroxynitrite and subsequent NF-kappaB activation, and the IL-8 appears to contribute to leukocytosis in tobacco smokers.

This paper presents a study carried out by a group of Japanese researchers to critically review past researches and discussions on the multifunctionality of paddy rice cultivation, with the aim of describing the current status of the subject and providing options and potentials for future research and practices. The review was of over 200 documented articles on the major external functions. The results of this study revealed that the importance of multifunctionality is well perceived in Japan. The methodologies to measure and estimate the magnitude have been established for most functions. However, there is a need for more cases, to integrate all the functions at the local or regional scale to represent site-specific characteristics of multifunctionality. There is also a need to develop management practices to sustain Y. Matsuno ( ) Kinki University, and enhance the positive multifunctionality of paddy rice cultivation while minimizing negative effects to the environment, which may be brought into the agricultural policies. Except for Korea, Taiwan, and Japan, there are slightly different notions on multifunctionality in other monsoon Asia countries, but the gap in this notion is reducing following recent international activities.

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The mutation in TAP2 (Val577) may be involved in SS-A autoantibody production and could be a genetic factor that determines susceptibility to SS.