巻号一覧
132 巻, 8 号
選択された号の論文の15件中1～15を表示しています
- |<
- <
- 1
- >
- >|
誌上シンポジウム
-
常盤 広明2012 年 132 巻 8 号 p. 861-862
発行日: 2012/08/01
公開日: 2012/08/01
ジャーナル フリーPDF形式でダウンロード (212K) -
吉澤 一成2012 年 132 巻 8 号 p. 863-871
発行日: 2012/08/01
公開日: 2012/08/01
ジャーナル フリーDensity functional theory (DFT) is now extensively used as a research tool for the investigation of structure and reactivity of biological systems; however, its high computational demands still restrict the applicability of DFT to systems of a few tens up to one hundred atoms. A combined quantum mechanical/molecular mechanical (QM/MM) approach is applicable as an important method to study whole enzyme systems more than ten thousands atoms. We have investigated methane monooxygenase, dopamenie β-monooxygenase, tyrosinase, B12 dependent diol dehydratase, etc. using DFT and QM/MM calculations. In particular, we have done some computational mutation analyses about the amino acid residues at the active site of diol dehydratase. Our DFT and QM/MM calculations can correctly describe the structures and activation barriers of intermediates and transition states in the protein environment, and therefore, we successfully revealed the catalytic role of amino acid residues at the active site of diol dehydratase. Predicted relative activities of mutants are consistent with experimentally observed reaction rates. These results encourage us to apply QM/MM research to enzymatic reactions, functional analysis of active-site residues, and rational design of enzymes with new catalytic functions.
抄録全体を表示PDF形式でダウンロード (1038K) -
桑田 一夫2012 年 132 巻 8 号 p. 873-879
発行日: 2012年
公開日: 2012/08/01
ジャーナル フリーWe developed a theoretical framework for the regulation of biological macromolecules using the logically designed compounds. According to the cohomology theory, algebraic objects can be translated into geometrical ones. Successfully established quantum theory at 20th century, which essentially deals with the non-commutative nature of the space, also suggests the non-commutative topology of biological space. Arithmetic geometrical representation of the molecules as well as the macroscopic membranous structures would uncover their structural groups in Hilbert space. In order to construct the concrete image of biological space, here we combined quantum chemical (QC) model, all-atom (AA) model and coarse grained (CG) model, into one program designated ‘NAGARA’. These three models can be arranged in an arbitrary manner to yield the desired statistical ensemble. For example, QC model was applied to the optimization of the chemical structure of anti-prion lead compound GN8. Arithmetic geometrical representation of these algebraic models is in progress.
抄録全体を表示PDF形式でダウンロード (414K) -
須原 義智, 元吉 沙也加, 廣田 佳久, 澤田 夏美, 中川 公恵, 常盤 広明, 岡野 登志夫2012 年 132 巻 8 号 p. 881-886
発行日: 2012/08/01
公開日: 2012/08/01
ジャーナル フリーVitamin K2 is a ligand for a nuclear receptor, steroid and xenobiotic receptor (SXR), that induces the gene expressions of CYP3A4. We synthesized new vitamin K analogues with the same isoprene side chains symmetrically introduced at the 2 and 3 positions of 1,4-naphthoquinone and vitamin K2 analogues with hydroxyl or phenyl groups at the ω-terminal of the side chain. The upregulation of SXR-mediated transcription of the target gene by the analogues was dependent on the length of the side chain and the hydrophobicity of the ω-terminal residues. Phenyl analogue menaquinone-3 was as active as the known SXR ligand rifampicin.
抄録全体を表示PDF形式でダウンロード (678K)
総説
-
八百板 康範2012 年 132 巻 8 号 p. 887-893
発行日: 2012年
公開日: 2012/08/01
ジャーナル フリーOver the past twenty years, our research group has been involved in the phytochemical study of terpenoids from Compositae plants. From seven species, namely, Erigeron annuus (L.) PERS., Erigeron philadelphicus L., Erigeron sumatrensis RETZ., Ligularia dentata HARA, Ligularia stenocephala MATSUM. et KOIDZ., Petasites japonicus MAXIM., and Tussilago farfara L., we isolated 83 new compounds. In this review, structural features of 19 eremophilane-type sesquiterpenoids from rhizomes of P. japonicus and 9 bisabolane-type sesquiterpenoids from roots of L. dentata are discussed.
抄録全体を表示PDF形式でダウンロード (570K) -
上村 聡志2012 年 132 巻 8 号 p. 895-901
発行日: 2012/08/01
公開日: 2012/08/01
ジャーナル フリーGlycosphingolipids (GSLs) exist in the outer leaflet of the plasma membrane, where they form lipid microdomains that function as platforms for the regulation of trans-membrane signal transduction. In mammals, complex GSLs differing in the number and/or type of sugar species are produced in a cell-type specific manner, and the variety of glycan structures in GSLs are believed to determine specific cell functions. The glycan moieties of GSLs are synthesized at the luminal side of the Golgi apparatus by multiple Golgi-resident glycosyltransferases. Since the expression levels of most endogenous glycosyltransferases are relatively low, their detection is generally difficult. Nevertheless, we have succeeded in detecting endogenous mouse GM3 synthase (GM3S), the primary glycosyltransferase responsible for the biosynthesis of ganglio-series gangliosides. Mouse GM3S (mGM3S) has three isoforms (M1-GM3S, M2-GM3S, and M3-GM3S), each with a distinct length in its NH2-terminal cytoplasmic tail. These isoforms are produced by leaky scanning from two mRNA variants, mGM3Sa and mGM3Sb. M1-GM3S is stably localized in the endoplasmic reticulum (ER), as a result of retrograde transport signals (arginine [R]-based motifs); consequently, its in vivo GM3 synthesis activity is very low compared with that of other isoforms. In contrast, both M2-GM3S and M3-GM3S are localized in the Golgi apparatus, yet each exhibits a distinct intracellular fate. M2-GM3S is rapidly degraded in the lysosomes, whereas M3-GM3S is retained in the Golgi apparatus. A system that produces GM3S isoforms having such distinct characteristics is likely to be of critical importance in the regulation of GM3 biosynthesis under various pathological and physiological conditions.
抄録全体を表示PDF形式でダウンロード (733K) -
土谷 博之2012 年 132 巻 8 号 p. 903-909
発行日: 2012/08/01
公開日: 2012/08/01
ジャーナル フリーNon-alcoholic fatty liver disease (NAFLD) is frequently associated with insulin resistance, suggesting its crucial role in the development and progression of NAFLD. We used a mouse model of high-fat, high-fructose (HFHFr) diet-induced NAFLD to examine the effects of retinoids on insulin resistance. Dietary administration of all-trans-retinoic acid (ATRA) significantly improved insulin sensitivity in C57BL/6J mice fed the HFHFr diet, and in KK-Ay mice but not in the leptin-deficient ob/ob mice. ATRA treatment significantly upregulated hepatic leptin receptor (LEPR) expression. In agreement with these observations, in vitro experiments showed ATRA directly induced LEPR gene expression through RARα. In the livers of C57BL/6J mice administered ATRA, insulin receptor substrate-1 (IRS1) was activated concomitantly with the phosphorylation of Janus kinase-2 and signal transducer and activator of transcription-3 (STAT3). STAT3 phosphorylation was also observed in KK-Ay but not in ob/ob mice. In in vitro experiments, ATRA significantly enhanced insulin-induced IRS1 tyrosine phosphorylation solely in the presence of leptin. A selective RARα/β agonist, tamibarotene, also enhanced hepatic LEPR expression, STAT3 phosphorylation, and ameliorated insulin resistance in KK-Ay mice. We discovered an unrecognized mechanism of retinoid action for the activation of hepatic leptin signaling, which resulted in enhancing insulin sensitivity in two mouse models of insulin resistance. Moreover, we also found that retinoids attenuate hepatic iron overload and iron-induced oxidative stress, which have recently emerged as an important factor for the development and progression of insulin resistance. Our data suggest that retinoids might have potential for treating NAFLD associated with insulin resistance.
抄録全体を表示PDF形式でダウンロード (392K) -
片岡 誠2012 年 132 巻 8 号 p. 911-917
発行日: 2012/08/01
公開日: 2012/08/01
ジャーナル フリーPositron emission tomography (PET) is a powerful and noninvasive technology for molecular imaging in living systems. Its high sensitivity and high spatial-temporal resolution make this technology particularly useful to analyze the disposition of drugs in the body. PET technology could be applied to analyze the process of distribution of orally administered drugs on the basis of time-profiles of radioactivity in vivo. Kinetic analysis of radioactivity derived from 18F-labeled 2-fluoro-2-deoxy-D-glucose administered orally to rats under several conditions indicated that not only gastric emptying and intestinal transit but also the rate constant of intestinal absorption and limited process of oral absorption could be evaluated quantitatively. After oral administration of 11C-labeled telmisartan with or without non-radiolabeled telmisartan, systemic bioavailability and hepatic distribution of radioactivity significantly increased non-linearly with dose. In the intestinal lumen, telmisartan and its glucuronide, converted by UDP-glucuronosyl transferase (UGT), were detected and the ratio of telmisartan decreased at a high dose of telmisartan. In vitro permeation study revealed that telmisartan is a substrate of P-glycoprotein (P-gp). It was reported that hepatic uptake of telmisartan is mediated by organic anion transporting polypeptide 1B3 (OATP1B3) and most of the hepatic radioactivity in the liver is derived from telmisartan. These results indicated that P-gp for intestinal absorption, OATP1B3 for hepatic uptake and UGT for glucuronidation could be considered as limiting steps of orally administered telmisartan. Therefore, PET study is highly anticipated to be a potent tool for better understanding of gastrointestinal absorption and the subsequent tissue distribution of various drugs and candidates.
抄録全体を表示PDF形式でダウンロード (618K) -
今村 大輔2012 年 132 巻 8 号 p. 919-924
発行日: 2012/08/01
公開日: 2012/08/01
ジャーナル フリーThe Gram-positive bacterium Bacillus subtilis forms spores when conditions are unsuitable for growth. The spores are encased in a multilayered shell that includes a cortex and a spore coat, and remain viable for long periods in the harsh environment. In the present article, recent progress in our understanding of the outer structure of B. subtilis spores is reviewed in the Japanese language. Although spore coat assembly involves the deposition of at least 70 distinct protein species, the positions of most of such proteins have not been experimentally determined. To this end, the diameters of the protein layers and spores were measured using fluorescence microscopy and then the positions of proteins in the spore coat of B. subtilis spores were estimated. The locations of 16 proteins were determined using this method. One protein was assigned to the cortex, nine to the inner coat, and four to the outer coat. Further, two proteins, CgeA and CotZ, were assigned to a previously unidentified outermost layer. McKenney et al. have also identified the outermost layer using a similar method; the layer was termed the “crust”. Immunofluorescence microscopy revealed that the crust is indeed the most external layer of B. subtilis spores. Mutational analysis indicated that all genes in the cotVWXYZ cluster were involved in spore crust synthesis and that CotY and CotZ played critical roles in crust formation.
抄録全体を表示PDF形式でダウンロード (597K) -
堤 広之2012 年 132 巻 8 号 p. 925-931
発行日: 2012/08/01
公開日: 2012/08/01
ジャーナル フリーTwo crystals of a complex of (−)-gallocatechin-3-O-gallate (GCg) with caffeine and crystals of the complexes of (+)-catechin (CA) and (−)-catechin-3-O-gallate (Cg) with caffeine were prepared, and their stereochemical structures and intermolecular interactions were determined in X-ray crystallographic analysis. GCg formed 1:2 and 2:2 complexes with caffeine, and π-π interactions formed between the aromatic rings of GCg and caffeine in both complexes. In addition, CA of nongalloylated catechins formed a 1:1 complex with caffeine through intermolecular hydrogen bonds, whereas Cg of galloylated catechins formed a 1:2 complex with caffeine, which was formed by face-to-face and offset π-π interactions and intermolecular hydrogen bonds.
抄録全体を表示PDF形式でダウンロード (770K)
一般論文
-
阪元 明日香, 中村 雅胤2012 年 132 巻 8 号 p. 933-937
発行日: 2012/08/01
公開日: 2012/08/01
ジャーナル フリーThis study evaluated the effects of flavin adenine dinucleotide (FAD) on ultraviolet B (UV-B)-induced damage in cultured human corneal epithelial (HCE-T) cells. The cultured HCE-T cells were treated with 0.003125-0.05% FAD before exposure to 80 mJ/cm2 UV-B. Cell viability was measured 24 h after UV-B irradiation using the MTS assay. Reactive oxygen species (ROS) were detected 30 min after UV-B irradiation using 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester. Apoptosis was evaluated 4 h after UV-B irradiation in the caspase-3/7 activity assay. UV-B irradiation reduced cell viability and stimulated ROS production and caspase-3/7 activity in HCE-T cells. Pretreatment of UV-B irradiated HCE-T cells with FAD significantly attenuated cell viability reduction and inhibited the stimulation of both ROS production and caspase-3/7 activity due to UV-B exposure compared with those with vehicle (0% FAD). These results clarified that FAD inhibits ROS-mediated apoptosis by UV-B irradiation in HCE-T cells and suggest that FAD may be effective as a radical scavenger in UV-B-induced corneal damage.
抄録全体を表示PDF形式でダウンロード (361K) -
中内 崇夫, 竹内 恵那, 岡本 拓也, 寺元 勝弥, 野崎 葵, 世古 風子, 弓樹 佳曜, 片川 純一, 橋本 直文2012 年 132 巻 8 号 p. 939-944
発行日: 2012/08/01
公開日: 2012/08/01
ジャーナル フリーThere are various opinions regarding the different functions of original and generic drugs. We used the paddle method to perform dissolution tests on pravastatin sodium tablets (10 mg) to investigate the causes for these differences. We used water and buffer solutions adjusted to pH 1.2 (JP1) and pH 6.8 (JP2), which are described in the Japanese Pharmacopoeia. The pravastatin concentration was measured by UV spectroscopy and HPLC. There were significant differences in the percentages dissolved of original and generic drugs after 5 and 10 min. On the other hand, the dissolution behaviors using water and JP2 measured by HPLC were similar to the results obtained by UV spectroscopy. However, the percentage dissolved of pravastatin using JP1 decreased with time because pravastatin degraded in JP1. There were also significant differences in the pravastatin concentrations of the original and generic drugs at 5, 15, 30, and 45 min. Based on the above results, since the original drug has a slower dissolution rate than the generic drugs, it is necessary to be cautious about the degradation of pravastatin in the stomach and the bioavailability of pravastatin due to the different dissolution rates and the different residual amount of pravastatin in the stomach.
抄録全体を表示PDF形式でダウンロード (573K) -
上村 直樹, 木下 教之, 翁長 みどり, 渡辺 ゆりか, 伊集院 一成, 鹿村 恵明, 根岸 健一, 海保 房夫, 太田 隆文2012 年 132 巻 8 号 p. 945-951
発行日: 2012/08/01
公開日: 2012/08/01
ジャーナル フリーPackage insert of pharmaceutical drug is one of the most prioritized information for pharmacists to secure safety of patients. However, the color of character, size, font and so on are various company by company product to product from a viewpoint of visibility. It may be cause a serious accident in case visibility is unclear, although it is the most important information. Moreover, package insert with high visibility is required for color vision defectives from a viewpoint of a universal design. Then, the authors selected the package insert which has the boxed warning in the ethical pharmaceutical currently stored mostly in the present health insurance pharmacy and quantified the red color using the color meter. We advocate the state of a suitable package insert from a viewpoint of a universal design, whether the red color is high visible or not for color vision defectives using simulator.
抄録全体を表示PDF形式でダウンロード (793K)
ノート
-
御舩 正樹, 岩藤 章正, 神野 伸一郎, 榎本 秀一2012 年 132 巻 8 号 p. 953-958
発行日: 2012/08/01
公開日: 2012/08/01
ジャーナル フリーOctabromo-tetrakis(4-methylpyridyl)porphine (OBTMPyP), an octabromonated compound with 4 pyrole rings of tetrakis(4-methylpyridyl)porphine, selectively forms a complex with Cu2+ ions at pH 2.0. When 3.6×10−5 mol/L OBTMPyP was added to the reaction mixture, the calibration curve showed good linearity for Cu2+ ions ranging from 0.01-2.2 µg (addition of 1.0 mL). A good coefficient of variation (Cu2+ions=1.5 µg (addition of 1.0 mL), n=10, 0.8%) was obtained. The molar absorption coefficient (ε) based on Cu2+ ions was 8.5×104 L/mol•cm. This value was 6-fold greater than that determined with a clinical chemical analysis kit using the bathocuproine sulfonic acid method, which is a well-known method for spectrophotometric determination of the Cu2+ ion concentration. A deproteination method was successfully applied in the clinical analysis kit for determination of Cu2+ ion concentrations in control serum I, and the values determined using this method and the bathocuproine sulfonic acid method were almost the same.
抄録全体を表示PDF形式でダウンロード (512K) -
伊佐間 和郎, 河上 強志, 西村 哲治2012 年 132 巻 8 号 p. 959-968
発行日: 2012/08/01
公開日: 2012/08/01
ジャーナル フリーThe International Standard ISO 8124-3:2010 “Safety of toys—Part 3: Migration of certain elements” controls the levels of migrated eight harmful elements (antimony, arsenic, barium, cadmium, chromium, lead, mercury and selenium) from infants toys. Moreover, the Japanese Food Sanitation Law controls the levels of migrated lead from metal accessory toys. However, the levels of migrated harmful elements from metal accessories that are not infants toys are not controlled, since they are not covered by the ISO Standard or the Food Sanitation Law. Therefore, we investigated the level of eight harmful elements migrated from metal accessories that infants may swallow by mistake. The extraction test of ISO 8124-3:2010 was executed in 117 products (total 184 specimens), and the concentration of these eight elements was measured by inductively coupled plasma mass spectroscopy (ICP-MS). As a result, 28 and one products released lead and cadmium beyond the maximum acceptable levels of the ISO standard, respectively. Metal accessories that infants may swallow by mistake should ideally not release harmful elements such as lead and cadmium.
抄録全体を表示PDF形式でダウンロード (958K)
- |<
- <
- 1
- >
- >|