Severe infestations of Alopecurus aequalis (shortawn foxtail), a noxious weed in wheat and barley cropping systems in Japan, can occur even after application of thifensulfuron-methyl, a sulfonylurea (SU) herbicide. In the present study, nine accessions of A. aequalis growing in a single wheat field were tested for sensitivity to thifensulfuron-methyl. Seven of the nine accessions survived application of standard field rates of thifensulfuron-methyl, indicating that severe infestations likely result from herbicide resistance. Acetolactate synthase (ALS) is the target enzyme of SU herbicides. Full-length genes encoding ALS were therefore isolated to determine the mechanism of SU resistance. As a result, differences in ALS gene copy numbers among accessions were revealed. Two copies, ALS1 and ALS2, were conserved in all accessions, while some carried two additional copies, ALS3 and ALS4. A single-base deletion in ALS3 and ALS4 further indicated that they represent pseudogenes. No differences in ploidy level were observed between accessions with two or four copies of the ALS gene, suggesting that copy number varies. Resistant plants were found to carry a mutation in either the ALS1 or ALS2 gene, with all mutations causing an amino acid substitution at the Pro197 residue, which is known to confer SU resistance. Transcription of each ALS gene copy was confirmed by reverse transcription PCR, supporting involvement of these mutations in SU resistance. The information on the copy number and full-length sequences of ALS genes in A. aequalis will aid future analysis of the mechanism of resistance.

Accumulating evidence suggests that activated mast cells are involved in contact hypersensitivity, although the precise mechanisms of their activation are still not completely understood. We investigated the potential of common experimental allergens to induce mast cell activation using murine bone marrow-derived cultured mast cells and rat peritoneal mast cells. Among these allergens, 1-chloro-2,4-dinitrobenzene and 1-fluoro-2,4-dinirobenzene (DNFB) were found to induce degranulation of rat peritoneal mast cells. DNFB-induced degranulation is accompanied by cytosolic Ca 2+ mobilization and is significantly inhibited by pertussis toxin, U73122 (a phospholipase C inhibitor), and BAPTA (a Ca 2+ chelator), raising the possibility that DNFB acts on the G protein-coupled receptors and activates G i , which induces activation of phospholipase C, as well as known mast cell secretagogues, such as compound 48/80. DNFB could induce mast cell degranulation in the absence of serum proteins and IgE. Structure-activity relationship analyses revealed an inverse correlation between the degree of degranulation and the electron density of the C1 carbon of the DNFB derivatives. These findings raise a possibility that DNFB functions as a potent contact allergen through induction of cutaneous mast cell degranulation.Keywords: Contact hypersensitivity r 1-Fluoro-2,4-dinitrobenzene r Histamine r Inflammation r Mast cells Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Prof. Satoshi Tanaka e-mail: tanaka-s@okayama-u.ac.jp IntroductionA series of recent studies have enriched our understanding about the pathology of contact hypersensitivity [1]. Contact hypersensitivity was initially recognized as an allergic responses induced C 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2017. 47: 60-67 Innate immunity 61 mainly by activated T cells but now is regarded as the complex process involving many kinds of immune cells in addition to T cells. Chemical compounds, such as 1-fluoro-2,4-dinitrobenzene (DNFB), oxazolone, and picryl chloride, have been used for induction of contact hypersensitivity [2]. These models have revealed that self-proteins conjugated with these compounds induced Tcell-mediated immune responses, which required dendritic cell migration. Although it has long been controversial whether mast cells are involved in contact hypersensitivity, a series of the transfer experiments has indicated that IgE and mast cells could initiate immune responses in several models [3,4]. Recent studies have expanded the pathological roles of IgE and cutaneous mast cells in murine contact hypersensitivity models [5,6]. Bryce et al. demonstrated that successful contact hypersensitivity with oxazolone should require mast cells equipped with IgE [7]. Cutaneous mast cells were found to promote dendritic cell migration into the draining lymph node, which is regarded as the primary step of contact hypersensitivity, through the release...

The main function of pharmaceutical care is to dispense drugs. The process of drug dispensing is getting simpler as a result of the development of automated dispensing systems, however the traditional dispensing system/process, manually selecting drugs from shelves and transferring the correct number of dose units to labeled paper bags, is complicated and still adopted in a majority of hospital pharmacies in Japan. The complicated dispensing process leads to human error. Thus, pharmacists must address and minimize human error in drug dispensing. To address human error in dispensing, we adopted a dispensing support system (Patient oriented risk management system: PORIMS) with using personal digital assistance (PDA). In this study, to evaluate efficiency PORIMS in dispensing incidents, we categorized dispensing incidents into 2 groups, prevented dispensing incidents (PreDIs) and dispensing incidents (DIs), and then investigated the number of dispensing incidents. Incidents were recorded and categorized when a pharmacist double-checked assembled products/medication. As a result, the total number of PreDIs was significantly reduced by using PORIMS, 52.4 to 39.5 /1,000 prescriptions/month (P < 0.001). Selection errors and forgetful dispensing were completely prevented. Counting errors were significantly reduced by recording the number of agents before assembly (13.85 ± 3.19 to 5.37 ± 1.15/month, P = 0.026). The use of PORIMS was associated with a decrease in the number of reports on drug dispensing errors. In this study, we clearly demonstrated that PORIMS should be useful in the prevention of human error in drug dispensing. PORIMS enhances the performance of pharmacists.Key words -dispensing error, dispensing incident, personal digital assistance, dispensing support system, recording the number of agents, safety management

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