YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
105 巻, 11 号
選択された号の論文の13件中1~13を表示しています
  • 宮澤 辰雄
    1985 年 105 巻 11 号 p. 1009-1018
    発行日: 1985/11/25
    公開日: 2008/05/30
    ジャーナル フリー
    Novel applications of nuclear magnetic resonance (NMR) spectroscopy in biochemistry are reviewed. The biological functions of peptides are correlated with the conformations of membrane-bound molecules rather than the conformations in aqueous solutions. The membrane-bound conformations may be elucidated by the analysis of transferred nuclear Overhauser effects. The conformations of nucleotide inhibitors as bound to ribonucleases may be analysed by nuclear Overhauser effect. Thus, ribonuclease T1 is found to have binding sites for guanine base and 3'-phosphate but not for 5'-phosphate group. From the 13C-NMR spectra of subtilisin inhibitors as labeled with [1-13C] Met and [15N]-Val, the inhibitor is found to form a Michaelis complex with subtilisin. From the proton NMR analyses of immunoglobin (IgG), the hinge region (indispensable for the activation of complement system) is found to be the most mobile. The uridine residue in the first position of anticodon of transfer ribonucleic acids (tRNA) are always modified after transcription. The conformational characteristics of the modified uridines have been elucidated by proton NMR analyses. The modifications of uridine in the first position of anticodon are now found to contribute to correct and efficient translations of codons, through the regulation of rigidity/flexibility of the anticodon moiety of tRNA.
  • 吉川 寛
    1985 年 105 巻 11 号 p. 1019-1028
    発行日: 1985/11/25
    公開日: 2008/05/30
    ジャーナル フリー
    Recent progress in our studies on mechanism and regulation of initiation of chromosomal replication in Bacillus subtilis is reviewed. The origin of the chromosomal replication, OriC, is supposed to be composed of deoxyribonucleic acid (DNA) signals for initiation of autonomous replication and its regulation. A 245 bp sequence essential for autonomous replication has been isolated from OriC of E. coli. In contrast, attempts to isolate a similar sequence from B. subtilis has not been successful, suggesting that B. subtilis OriC is more complicated in structure and function than that of E. coli. To study structure and function of the B. subtilis OriC region, we first cloned some 50 kbp DNA in the origin region and determined the exact site of OriC in vivo within 1000 bp on each strand of the chromosome. The initiation site on each strand is located some 2 kb apart and replication proceeds inward to pass the other site, indicating the one strand be leading the other be lagging strand. Second, we have determined DNA sequence of 12 kbp around the OriC. Computer analysis of the sequence, determination of transcription in vivo by S-1 mapping and identification of gene products by the Maxi-cell method revealed 10 open reading frames (ORF=genes) which constitute 6 transcriptional units. The ORFs are identified by genetic evidence and comparison with known genes in E. coli. They are from left to right "RnpA"-"RpmH"-"DnaA"-"DnaN"-URF (unknown ORF) 71-RecF-URF52-GyrB-GyrA-RrnO. These genes are essential for cell growth involving in synthesis of DNA or ribonucleic acid, or in changes in DNA structure. Not only individual genes but also their organization is highly conserved between B. subtilis and E. coli. Two regulatory regions are found flanking "DnaA" gene. We concluded that they are B. subtilis OriC because 1. they contain 9 and 4 repeating sequences whose consensus sequence TTAT (C/A) CACA is identical to DnaA protein binding site in E. coli oriC, 2. transcription from within these regions parallels initiation of chromosomal replication. In contrast to E. coli OriC these regions do not replicate autonomously, instead inhibit plasmid replication when they are inserted into it. Difference in organization of OriC in relation to the regulatory gene "DnaA" may be responsible for the difference in OriC function between the two bacteria.
  • 荒川 良夫, 深谷 力, 山内 紘一, 横山 和正
    1985 年 105 巻 11 号 p. 1029-1033
    発行日: 1985/11/25
    公開日: 2008/05/30
    ジャーナル フリー
    The photochemical reaction of dexamethasone 21-acetate (1) was studied to explore the influence of 11β-hydroxy group on the photochemical process of a cross-conjugated dienone system. Irradiation of 1 in methanol gave the lumi-product (2) and its two isomers, 1β, 11β-epoxy-9α-fluoro-17α-21-dihydroxy-16α-methyl-10α-pregn-4-ene-2, 20-dione 21-acetate (3) and 2, 5-cyclo-1β, 11β-epoxy-9α-fluoro-2β, 17α, 21-trihydroxy-16α-methyl-5β, 10α-pregn-3-en-20-one 21-acetate (4). Compound 2 was proved to be an intermediate for 3 and 4.
  • 呉 立軍, 宮瀬 敏男, 上野 明, 黒柳 正典, 野呂 忠敬, 福島 清吾, 佐々木 [サトシ]
    1985 年 105 巻 11 号 p. 1034-1039
    発行日: 1985/11/25
    公開日: 2008/05/30
    ジャーナル フリー
    Four new flavanonols, kushenol J (I), kushenol K (II), kushenol L (III) and kushenol M (IV), were isolated from the dry roots of Sophora flavescens AIT. (Leguminosae). Their structures were elucidated on the basis of spectral data especially 1H nuclear magnetic resonance and 13C nuclear magnetic resonance. It is the first case that the isolation of a flavonoid glycoside (I) and a cis flavanonol (II) derivatives from Sophora flavescens AIT.
  • 内多 稔, 田房 不二男, 小松 真, 森田 誠治, 神辺 敏実, 中川 量之
    1985 年 105 巻 11 号 p. 1040-1045
    発行日: 1985/11/25
    公開日: 2008/05/30
    ジャーナル フリー
    A series of 3-aromatic ring substituted 2-(4-chlorobenzoylamino) propionic acids was synthesized and tested for antiulcer activity towards the acetic acid-induced gastric ulcer in the rat which is a model of a chronic ulcer. 2-(4-Chlorobenzoylamino) propionic acid derivatives were prepared by the reaction of halomethyl or methanesulfonyloxymethyl substituted aromatic compounds with diethyl 4-chlorobenzoylaminomalonate, or by the 4-chlorobenzoylation of α-amino acids. Among the propionic acid derivatives thus synthesized, α-(4-chlorobenzoylamino)-2, 3-dihydro-2-oxo-1H-indole-3-propionic acid was found to have a potent antiulcer activity. The structure-activity relationships are discussed.
  • 大竹 英俊, 湯浅 英雄, 小村 千世子, 宮内 徹二, 萩原 義秀, 久保田 和彦
    1985 年 105 巻 11 号 p. 1046-1051
    発行日: 1985/11/25
    公開日: 2008/05/30
    ジャーナル フリー
    Antiulcer activity of green juice from young barley leaves and of fractions from the green juice was examined. Fractions containing water soluble proteins and water soluble organic compounds showed significant antiulcer activity in the stress-, acetic acid- and aspirin-induced stomach ulcer at an oral dose of 500 mg/kg. A fraction containing water insoluble substances also showed antiulcer activity in the stress- and acetic acid-induced ulcer. Those fractions affected neither the secretion of acid and pepsin from the stomach nor the absorption of aspirin from the gastrointestinal tract. These findings suggest that the antiulcer action of the fractions may be due to the protection of the stomach mucosa from injury by attacking factors.
  • 大竹 英俊, 野中 涼代, 澤田 淑子, 萩原 義秀, 萩原 秀昭, 久保田 和彦
    1985 年 105 巻 11 号 p. 1052-1057
    発行日: 1985/11/25
    公開日: 2008/05/30
    ジャーナル フリー
    Hypocholesterolemic effects of green juice from young barley leaves were investigated on hypercholesterolemia in rats fed on a high cholesterol diet (HCD). The n-hexane extract from a water insoluble fraction of green juice showed hypocholesterolemic activity. At least two substances responsible for the hypocholesterolemic effects were isolated from the n-hexane extract and purified by silica gel chromatography. One of them was β-sitosterol, and the other n-hexacosyl alcohol which was a saturated higher alcohol having a molecular weight of 382. In the rats fed on HCD added with n-hexacosyl alcohol at a concentration of 1%, the plasma cholesterol level was hardly lowered on day 3 but markedly on day 9. In a similar experiment, β-sitosterol markedly lowered the plasma cholesterol level of rats on both day 3 and day 9. Through these experiments, we found that barley leaves contained hypocholesterolemic substances, and that two compounds such as β-sitosterol and n-hexacosyl alcohol were responsible for the hypocholesterolemic activity.
  • 増池 健年, 渡辺 幾代, 武本 宜教
    1985 年 105 巻 11 号 p. 1058-1064
    発行日: 1985/11/25
    公開日: 2008/05/30
    ジャーナル フリー
    A high performance liquid chromatographic (HPLC) method has been developed to determine simultaneously 5-fluorouracil (5-FU) and its metabolites, 5-fluorodeoxyuridine (FUdR) and 5-fluorouridine (FUR), in various biological samples. 5-FU and its metabolites in these samples were cleaned up by solvent extraction and/or preparative column chromatography. The pretreated samples were dissolved in a mixture of mobile phase for HPLC (see below) and n-hexane (3 : 2). An aliquot of these solutions was injected onto silica gel column (4.6×50 mm, 3 μm, 60 A), and eluted with a mobile phase of ethylacetate-n-hexane-formic acid (88%)-water (60 : 40 : 0.5 : 0.2), and the eluate was monitored at 264 nm. The quantitation limits of 5-FU, FUdR, and FUR were 0.02, 0.05, and 0.2μg/ml (or g), respectively. The present method was applied to various samples from 5-FU-administered rabbits and a patient. The results were compared with those determined by a bioassay method.
  • 長廻 貞雄, 板倉 忠則, 片桐 義博, 佐伯 孝雄
    1985 年 105 巻 11 号 p. 1065-1070
    発行日: 1985/11/25
    公開日: 2008/05/30
    ジャーナル フリー
    A high performance liquid chromatographic method is described for the determination of pyridoxal-5'-phosphate (PLP) in injections. PLP in injections exists as an adduct of sodium bisulfite, and is not easily separated on the reverse-phase C18 column as a single peak. The present method is based on the conversion of the adduct to PLP by treatment with excess pyridine-4-aldehyde. The recovery of PLP from various infusion fluids added with PLP was 97.6-100.5%. The recovery of PLP in the presence of its photodecomposition products was 98.1-102.8%. The method was not influenced by the constituents of infusion fluids and PLP photodecomposition products. The method provided a simple and rapid procedure for the evaluation of the quality and stability of PLP preparations under clinical conditions.
  • 河野 健治, 仲井 由宣
    1985 年 105 巻 11 号 p. 1071-1077
    発行日: 1985/11/25
    公開日: 2008/05/30
    ジャーナル フリー
    Crystallizing behavior of the ground cyclodextrins and the ground mixtures of cyclodextrins with medicinals were investigated at various relative humidities (RH) by powder X-ray diffraction and thermal method. The ground α-cyclodextrin, being in amorphous state at 68% RH, turned into crystals at 84% RH. The ground mixtures of cinnamic acid with α-cyclodextrin (molar ratio 1 : 2) crystallized at 84% RH. From the X-ray diffraction patterns the crystals were identified as an inclusion compound. On the other hand, the ground mixtures of diazepam with α-cyclodextrin (weight ratio 1 : 9) transformed not into inclusion compound crystals but into diazepam and α-cyclodextrin crystals at 84% RH. For all combinations of cyclodextrins with medicinals used in this experiment, the crystallization of the ground mixtures did not occur at 68% RH while it occurred at 84% RH in two ways along including behaviors in solution, that is the ground mixtures of host-guest combinations which produced the inclusion compound in solution turned into inclusion compound crystals by adsorbing water vapor, and those of producing no inclusion compound crystallized into respective component crystals separately.
  • 佐藤 秀昭, 江戸 清人, 水柿 道直
    1985 年 105 巻 11 号 p. 1078-1086
    発行日: 1985/11/25
    公開日: 2008/05/30
    ジャーナル フリー
    Extra-weak chemiluminescence of 120 kinds of Kampo Extracted Herbal Drugs were measured. These Kampo Extracted Herbal Drugs showed chemiluminescence values of 0 to 100 counts/10 s, 0 to 400 counts/10 s and 50 to 12000 counts/10 s, at 20, 50, and 80°C, respectively. Among the Kampo Extracted Herbal Drugs tested in this Gui-Zhi-Jia-Long-Gu-Mu-Li-Tang, Gui-Pi-Tang, Dang-Gui-Shao-Yao-San, Bu-Zhong-Yi-Qi-Tang and Jia-Wei-Gui-Pi-Tang showed high chemiluminescence values. In addition, it is suggested that the Kampo Extracted Herbal Drugs which generate high emission intensity are composed of crude drugs such as Zingiberis Rhizoma, Atractylodis Lanceae Rhizoma, Zizyphi Fructus, Angelicae Radix and Hoelen.
  • 後藤 茂, 川田 昌和, 中村 正宏, 青山 敏信
    1985 年 105 巻 11 号 p. 1087-1095
    発行日: 1985/11/25
    公開日: 2008/05/30
    ジャーナル フリー
    A microencapsulation of drugs using Eudragit RS which are copolymers synthesized from acrylic and methacrylic acid esters with a low content of quaternary ammonium groups, was investigated. The preparation is based on dispersion of methylene chloride containing drugs, Eudragit RS and magnesium stearate in purified water, followed by evaporation of methylene chloride using a well-regulated water bath. Magnesium stearate was used to reduce the flocculation of microcapsules in the preparation. Although 42 drugs were examined, only three drugs (sulfamethizole, furosemide and piretanide) were successful. The microcapsules just after separation from purified water were swollen due to hydrophilic groups of Eudragit RS. Furthermore, the swelling tendency increased in linearly with increasing addition percentages of magnesium stearate. The most suitable percentages of magnesium stearate for the preparation of microcapsules could be confirmed in this experiment. The microcapsules obtained after drying under reduced pressure were uniform and free-flowing particles. The dissolution rates of drugs from these microcapsules were relatively small compared to that from drug powders.
  • 中川 久, 西山 要, 東谷 敏夫, 石川 維孝, 福井 義雄
    1985 年 105 巻 11 号 p. 1096-1099
    発行日: 1985/11/25
    公開日: 2008/05/30
    ジャーナル フリー
    Pretreatment methods applicable to routine high performance liquid chromatography determination of ampicillin (ABPC) in many samples at plasma level concentration were examined and the deproteinization by phenol was found to be most suitable. The method consists of deproteinization of plasma by phenol, separation of ABPC (separation column ; Lichrosorb RP-8, mobile phase ; tetrahydrofuran : 0.02M phosphate buffer (pH 7.0)=1 : 30, flow rate ; 1 ml/min), post-column labeling with fluorescamine and measurement of fluorescence intensity at excitation wavelength of 385 nm and emission wavelength of 480 nm. ABPC was spiked in the plasma in the range of 0.05 to 10 μg/ml and the calibration curve showed a linear relationship (r=1.000), the limit of detection being 0.01 μg/ml. By use of this method, variation of ABPC concentration in the human plasma after oral administration of talampicillin, a prodrug of ABPC, was measured. As a result of comparative analysis, good correlation was found between this method and bioassay (r=0.990).
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