YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
123 巻 , 5 号
選択された号の論文の12件中1~12を表示しています
総説
  • 板谷 泰助
    原稿種別: その他
    専門分野: その他
    2003 年 123 巻 5 号 p. 267-283
    発行日: 2003年
    公開日: 2003/05/07
    ジャーナル フリー
    This review highlights the first total synthesis of (αS, βS)-β-hydroxywybutosine, the identity of which was established with fluorescent nucleoside isolated from rat liver tRNAPhe. Three general prerequisites for the synthesis of the target are emphasized: construction of new 9-β-D-ribofuranosyl-3-methylpurines; the first syntheses of optically active γ-aryl-α,β-unsaturated amino acids; and a new method for hydrogenolysis of glycols through their cyclic carbonates to give the γ-aryl-β-hydroxy amino acid derivatives. The mechanism for the formation of cyclic carbonates from reactions of glycols with (COCl)2 and highly selective preparation of the cyclic oxalates are also described.
  • 宮部 豪人
    原稿種別: その他
    専門分野: その他
    2003 年 123 巻 5 号 p. 285-294
    発行日: 2003年
    公開日: 2003/05/07
    ジャーナル フリー
    This review summarizes the new carbon-carbon bond construction methods based on the radical reaction of imine derivatives. The intermolecular carbon radical addition to oxime ethers proceeded smoothly in the presence of BF3·OEt2. A high degree of stereocontrol in the reaction of oxime ethers was achieved to give amino acid derivatives with excellent diastereoselectivities. The radical reaction of imine derivatives in water has also been investigated. The radical cyclization of oxime ethers proceeded effectively to provide the functionalized heterocycles via a carbon-carbon bond-forming process. These reactions were extended to the solid-phase radical reactions using triethylborane or diethylzinc as a radical initiator.
  • Ajoy Kumar GHOSH
    原稿種別: Review
    2003 年 123 巻 5 号 p. 295-303
    発行日: 2003/05/01
    公開日: 2003/05/07
    ジャーナル フリー
    In an air pouch-type carrageenin-induced inflammation model in rats, the selective cyclooxygenase (COX)-2 inhibitor NS-398 dose dependently inhibited the granulation tissue formation, angiogenesis and the level of vascular endothelial growth factor (VEGF) in the granulation tissue. In culture of the minced granulation tissue, PGE2 induced VEGF production in a concentration-dependent manner. Histamine also induced VEGF production in the granulation tissue in vitro. The H2 receptor antagonist cimetidine, the cAMP antagonist Rp-cAMP and the protein kinase A inhibitor H-89 suppressed the histamine-induced VEGF production in the granulation tissue. However, the H1 receptor antagonist pyrilamine maleate, the H3 receptor antagonist thioperamide, the protein kinase C inhibitors Ro 31-8425 and calphostin C or the tyrosine kinase inhibitor genistein showed no effect. Subcutaneous implantation of a cotton thread in the dorsum of histidine decarboxylase-deficient (HDC−/−) mice, but not in mast cell-deficient (WBB6F1-W/WV) mice, induced less angiogenesis with lower levels of VEGF in the granulation tissue than in their corresponding wild-type (HDC+/+ and WBB6F1-+/+) mice. In HDC−/− mice, the topical injection of histamine or the H2 receptor agonist dimaprit rescued the defective angiogenesis and granulation tissue formation. In addition, cimetidine but not pyrilamine maleate and thioperamide inhibited the histamine-induced angiogenesis in the granulation tissue in HDC−/− mice. These findings suggest that PGE2 and histamine augment angiogenesis in the inflammatory granulation tissue by inducing VEGF production, and histamine induces VEGF production possibly through the H2 receptor—cAMP—protein kinase A pathway.
  • 田中 好幸
    原稿種別: その他
    専門分野: その他
    2003 年 123 巻 5 号 p. 305-313
    発行日: 2003年
    公開日: 2003/05/07
    ジャーナル フリー
    Biologically active RNA molecules utilize metal ions to fold into specific conformations or to form a catalytic center. Hammerhead ribozymes also contain a metal ion-binding motif in their conserved core region. This motif and bound metal ions have recently been focused on from the viewpoint of whether the metal ions are a catalytic metal or a structural metal. We studied the interaction between metal ions and an RNA oligomer, r(GGACGAGUCC), which mimics the metal ion-binding motif of hammerhead ribozymes, using NMR spectroscopy in solution. Using 15N-labeled RNA oligomers, the chemical shift of N7 of the G7 residue [N7(G7)] in the metal ion-binding motif was specifically perturbed upon the addition of Cd(II). It was also found that the 31P resonance of the phosphate of the A9 residue showed the largest perturbation of all the 31P resonances during titration. These data indicate that divalent cations can bind to the metal ion-binding motif in solution, and that the binding sites for cations are N7(G7) and the phosphate of A9. More importantly, the metal ion-binding motif is an independent functional module that can capture divalent cations without the assistance of other conserved residues in hammerhead ribozymes.
  • 左  一八
    原稿種別: その他
    専門分野: その他
    2003 年 123 巻 5 号 p. 315-322
    発行日: 2003年
    公開日: 2003/05/07
    ジャーナル フリー
    We first examined the involvement of the complex sphingolipids in cell-substratum adhesion using GM-95, a mutant cell line deficient in glycosphingolipids (GSLs) due to the lack of ceramide glucosyltransferase activity. We determined the adhesion of the mutant cells and stable transfectants expressing GSLs, which were established by transfection of GlcT-1 cDNA into GM-95 cells under neutral sphingomyelinase (sm) treatment. We confirmed that complex sphingolipids play critical roles in cell-substratum adhesion, and the presence of either GSLs or SM is sufficient for the adhesion. We also investigated intracellular signaling (glycosignaling) mediated by endogenous GM1a involved in the neuronal differentiation of PC12 cells using the cholera toxin B subunit (CTB) that specifically binds to ganglioside GM1a. Treatment with CTB induced neuron-like differentiation of PC12 cells. Biochemical analyses demonstrated that the tyrosine phosphorylation induced by CTB was responsible for neuron-like differentiation of PC12 cells and that the MEK-ERK cascade is a part of the biological signals mediated by endogenous ganglioside GM1a on PC12 cells. We further demonstrated that glycosignaling is mediated through a high-affinity ligand, PSGL-1, for P-selectin on neutrophils. In this case, engagement of PSGL-1 on the cell surface strongly induced tyrosine phosphorylation of several cellular proteins including ERKs and activated a canonical MAP kinase pathway. Tyrosine phosphorylation induced by engagement of PSGL-1 is responsible for the secretion of interleukin-8 from neutrophils, suggesting that PSGL-1-mediated glycosignals are involved in the progression of the inflammatory response. In this review, we mainly discuss the biological and pathological significance of glycoconjugates in relation to the above issues.
  • 稲垣 雅尚
    原稿種別: その他
    専門分野: その他
    2003 年 123 巻 5 号 p. 323-330
    発行日: 2003年
    公開日: 2003/05/07
    ジャーナル フリー
    Various 1,2-isothiazolidine-1,1-dioxide (γ-sultam) derivatives containing an antioxidant moiety, 2,6-di-tert-butylphenol substituent, were prepared. Some compounds that have a lower alkyl group at the 2-position of the γ-sultam skeleton showed potent inhibitory effects on both cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO), as well as production of interleukin-1 (IL-1) in in vitro assays. They also proved to be effective in several animal arthritic models without any ulcerogenic activities. Among these compounds, (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide (S-2474) was selected as an antiarthritic drug candidate. The structure-activity relationships examined and some pharmacological evaluations are described. Furthermore, we have developed an efficient and E-selective synthesis of S-2474, in which α-methoxy-p-quinone methide is used as a key intermediate. α-Methoxy-p-quinone methide was revealed to be equivalent to a p-hydroxy-protected benzaldehyde. It reacts smoothly with α-sulfonyl carbanion to give 1,6-addition intermediates, which can be further processed to provide S-2474 directly in the presence of a base. This procedure gives S-2474 as an almost single isomer on the benzylidene double bond in excellent yield and thus is a very practical method adaptable to large-scale synthesis. The detailed mechanistic aspects are studied and discussed.
一般論文
  • 石本 敬三, 石原 美和子, 岡田 典子, 足立 タツ子, 神谷  晃
    2003 年 123 巻 5 号 p. 331-336
    発行日: 2003/05/01
    公開日: 2003/05/07
    ジャーナル フリー
    Even if drugs are accurately dispensed, it is difficult to ensure their safety in the absence of an error-free medication system when or after drugs are given to patients. In particular, most powders are white and are impossible to distinguish based on appearance after thay are placed in powder packages. In this study, we newly developed a system in which prescription order information is bar-coded on drug envelopes, and read when powder is folded, facilitating efficient and accurate printing of the patient's name and drug name on powder packages. Seventy-one (86%) of 83 nurses surveyed indicated that the system was useful for resolving high-risk problems they had experienced: “when powder was taken from the envelope, the contents were unknown”, and “the powder was administered to another patient.”
  • 小橋 精一, 久保  元, 山内 貴靖, 東山 公男
    2003 年 123 巻 5 号 p. 337-347
    発行日: 2003/05/01
    公開日: 2003/05/07
    ジャーナル フリー
    6-Acyldecahydro[1,6]naphthyridines were synthesized as derivatives of matrine-type and allomatrine-type alkaloids, and the structure-activity relations were examined by the acetic acid-induced abdominal contraction test. All synthesized derivatives produced the antinociception in mice. The antinociceptive potencies of 15ac and 16ac were lower than those of 17ac, 18ac, 19ac and 20ac. Furthermore, those of the matrine-type derivatives 17b and 17c are greater than other derivatives. These findings suggest that less hindered tertiary amine and highly lipophilic acyl group are better functional groups for the greater antinociceptive potencies. Furthermore, these findings suggest that A or B ring of 1 and 2 are not essential for the antinociceptive effect.
  • 大高 怜子, 前田 昌子, 岩上 猛, 植田 泰輔, 木村 良夫, 今井 一洋, 四方田 千佳子, 松田 りえ子, 林 譲
    2003 年 123 巻 5 号 p. 349-355
    発行日: 2003/05/01
    公開日: 2003/05/07
    ジャーナル フリー
    The internal standard methods are known to compensate for the errors from sample preparation and injection into an analytical instrument. However, recent HPLC apparatuses have injectors of excellent repeatability and it is dubious whether the cancellation of injection error can lead to substantial improvement in the precision of analysis. This paper answers the above question experimentally and theoretically. The HPLC analysis of butylscopolamine bromide is taken as an example. The relative standard deviations (RSD) of measurements in the internal standard method and absolute calibration curve method are compared and the advantages of these methods are discussed. The measurement RSD is shown to be well estimated by the (function of mutual information) (FUMI) theory without repeating measurements. This report also demonstrates simple equations for calculating the measurement RSD at an arbitrary concentration of analyte and for selecting the better method between the internal standard method and absolute calibration curve method under specific experimental conditions.
ノート
  • 有田 悦子, 細谷 未佳, 谷古宇  秀, 加賀谷  肇, 河合 典子, 近藤 芳子
    原稿種別: その他
    専門分野: その他
    2003 年 123 巻 5 号 p. 357-364
    発行日: 2003年
    公開日: 2003/05/07
    ジャーナル フリー
    We evaluated error prevention education by clarifying the association between dispensing error factors and behavioral characteristics of pharmacists. The subjects were 98 pharmacists (27 men and 71 women) with a mean age of 29.7 years who gave informed consent for participation in our survey. Between November 2001 and January 2002, a questionnaire survey on dispensing errors was performed using the “Tokyo University Egogram, New Version” for the assessment of behavioral characteristics and the “Safety Behavior Questionnaire” for the assessment of error factors. An association was observed between the incidence of dispensing errors and behavioral characteristics. There was also an association between error contents and behavioral characteristics as well as error factors. With more experience, errors associated with becoming accustomed increased, suggesting that error prevention education is necessary not only for newly qualified pharmacists but also for managers.
  • 加藤 隆児, 大井 一弥, 上野 和行
    2003 年 123 巻 5 号 p. 365-368
    発行日: 2003/05/01
    公開日: 2003/05/07
    ジャーナル フリー
    Paroxysmal supraventricular tachycardia (PSVT) is a reentrant tachycardia, and the autonomic nervous system influences the paroxysms of PSVT. Tofisopam (Grandaxin®) is a derivative of benzodiazepines. It is reported that heart rate variability (HRV) reveals the function of the autonomic nervous system and is used as an index of the effects of the autonomic nervous system on the heart rhythm. In previous studies, it was reported that tofisopam improved HRV. In this case report, the frequency of PSVT was significantly decreased and subjective symptoms of arrhythmia were eliminated after the administration of tofisopam. R-R interval variability and high-frequency power (HF; 0.15—0.40Hz) were increased, and {low-frequency power (LF; 0.04—0.15Hz)}/HF was decreased after administration of tofisopam. These results suggest that tofisopam overcame the existing imbalance of the sympathetic and vagus nervous system. In this case report, it is suggested that tofisopam is effective for the treatment of PSVT.
資料
  • 西村 益浩, 矢口 寛, 吉次 博紀, 内藤 真策, 佐藤 哲男
    原稿種別: Others
    専門分野: Others
    2003 年 123 巻 5 号 p. 369-375
    発行日: 2003年
    公開日: 2003/05/07
    ジャーナル フリー
    Pairs of forward and reverse primers and TaqMan probes specific to each human cytochrome P450 isoform were prepared. Analysis of the mRNA level of each CYP isoform in total RNA from pooled specimens of various human organs was performed by real-time reverse transcription PCR using an ABI PRISM 7700 sequence detector system. The expression of CYP3A4 mRNA was similar to that of CYP3A7 mRNA in the fetal liver, and CYP3A4 mRNA levels in the fetal liver were about 0.1 times lower than in the adult liver. CYP2E1 showed the highest level of mRNA expression in the liver. The mRNA expression of 30 CYP isoforms (CYP1A1, 1A2, 1B1, 2A6, 2A7, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2J2, 3A4, 3A5, 3A7, 4A11, 4F2, 4F3, 5A1, 7B1, 8A1, 8B1, 17, 26A1, 27, 27B1, 39A1, 46, and 51) in the liver was successfully detected by this method. CYP2F1, 4B1, 4F8, 11s (11A, 11B1, and 11B2), 19, and 24 mRNA levels were the highest in the lung, lung, prostate, adrenal gland, placenta, and kidney, respectively; however, the mRNA expression of these eight CYP isoforms in the liver was not detected by this method. The mRNA levels of the CYP isoforms determined in various human tissues were in good agreement with previously reported data. The method described here has the advantages of high specificity and excellent quantification over a wide range of mRNA concentrations, making it suitable for the evaluation of a large number of samples in the assessment of the expression profile of drug-metabolizing enzymes.
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