ラットに

3H

-CU-

83

(S)を25μg/kgで静脈内あるいは経口投与し，血液中濃度および尿糞中排泄を検討した．
静脈内投与後の血液中濃度推移は投与後

5

分より上昇し，投与後45分に25.74ng eq./mlのC_maxを示し，それ以後t_1/2

3

.05時間とt_1/2 33.09時間の二相で減少した．投与後72時間までのAUCは135.42ng eq.·hr/mlであった．
経口投与では，投与後

3

時間でC_max 4.10ng eq./mlに達し，以後t_1/2α 4.46時間とt_1/2β 26.

83

時間の二相で減少した．投与後72時間までのAUCは48.62ng eq.·hr/mlであった．
静脈内投与と経口投与のいずれの場合も，尿および糞中への放射能の排泄は，投与後48時間でほぼ終了した．静脈内投与では，投与後72時間までに投与量の30.52%が尿中に，60.42%が糞中に排泄された．経口投与では，同じく72時間までに40.34%が尿中に，69.24%が糞中に排泄された．

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Background

The differences in conditions of enteric-coated acid-labile drug release and absorption between healthy subjects in bioequivalence studies and gastrointestinal patients in clinical practice can lead to significant differences in gastric stability of original PPIs and generics. Thus, pathologic duodenogastric reflux (PDGR) and the pH increasing within PPIs administration still remain unaccounted for.

Methods

Two-stage modified comparative dissolution testing of original omeprazole (OO) and four generics (G1;2;

;4) was performed. At first, we moved drugs from solution with pH 1.2 (1.2±0.05) to pH 7.0 (7.0±0.05) and measure concentration of omeprazole in solution by high-performance liquid chromatography. According to our self-developed formula, pH 7 exposure time of resistance to PDGR for omeprazole is 4 minutes, i.. the active substance should not be released within 4 minutes at pH 7. The exposure at the second stage was conducted with pH 4 (4.0±0.05), that imitated gastric pH after PPI administration. And then we also moved drugs to pH 7 with the subsequent measurement of omeprazole concentration.

Results

Omeprazole concentrations after 4, 10, 15, 20, 30, 45, 60 minutes in pH 7 solution at the first stage were different for OO and generics. For OO, these values were 4,7±0,7%; 41,4±

,0%; 62,±4,0%; 79,±2,%; ,±2,%; 81,±2,%; 80,±4,4%; for Generic1 - 0; 49,±,%; 88, ±2,%; 90,4±,7%; 88, 2±2,2%; 87,±2,0%; 85,±1,1%; for Generic2 - 0; 30,±,%; 66,7±,2%; 76,4±7,4%; ,±,%; 86,0±,7%; ,±,%: for Generic - 80,±,%; ,±1,%; , ±,2%; ,±2,7%; 81,±2,1%; ,1±2,0%; ,0±2,4%; for Generic4 - ,±1,7%; ,4±0,%; ,2±1,2%; , ±0,%; ,±0,%; ,±0,%; ,±1,1%, respectively.

An analysis of the omeprazole concentration in pH 7 solution at the second stage revealed the following parameters after the same time: for OO - 4,4±0,

%; 40, ±,0%; 62,±2,0%; 80,0±,1%; 85,4±2,%; ,±,4%; 80,±,%; for Generic1 - 0; 67,0±7,%; ,7±2,%; 91, ±4,%; ,1±1,%; 88,±1,4%; 87,±1,2%; for Generic2 - 0; 42,2±,%; 75,1±7,%; 81,0±,0%; 88,4±,2%; 88, ±1,%; 87,±1,0%; for Generic4 - 85,±0,%; 85,±0,%; ,7±0,%; ,7±,0%; ,4±0,%; ,4±0,%; ,±0,4%, respectively. Generic release and degradation were completely realized at pH 4.

Conclusion

Decreased gastric stability of Generic

and Generic4 makes PDGR and inhibited gastric acid secretion due to PPIs administration the potential causes of decreased enteric-coated acid-labile drugs stability.

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1. The chromosome numbers of 64 species have been studied on which 56 are investigated for the first time.
2. Morphological, anatomical and cytological findings on the Musaceae in the broad sense are considered from a phylogenetical standpoint and three distinct groups:
a) Musa-Ensete, ) Ravenala-Strelitzia-Phenakospermum and ) Holiconia are recognised as suggested by some authors. For these groups sub-familial status is proposed.
. Lowiaceae have been studied for the first time cytologically and their chromosome morphology, distinct from that of any other group of Zingiberales, confirms their claim to familial status.
4. Consideration of the conflicting theories proposed to account for the higher chromosome number in genera like Globba, Alpinia, and Phaemeria, etc. leads to rejection of Chakravorti's hypothesis of wholesale fragmentation of chromosomes and the acceptance of the opposed view of Raghavan and Venkatasubban and others.
. Holttum's transference of the genus Zingiber to the tribe Hedychieae has been given cytological support on the following points:
a) the basic number in the genus Zingiber correlates with that of Kaempferia.
) the new tribe Alpinieae (which is infact Zingibereae without Zingiber) have consistently 48 chromosomes in their somatic complements.
. It is suggested that the African representatives of Kaempferia should be given the status of genus; Cienkowskya on the following points:
a) the difference in floral morphology
) geographical separateness and
) the difference in the number and morphology of the chromosomes. By comparing the present and past findings, various lines of evolution of the chromosome complements within each group are discussed.
7. The basic number 11 is considered to be probably the original one for the Zingiberales as a whole, being present in Ravenala which is the most primitive member in the order. From this secondary basic numbers have arisen through evolution.

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The acetone extracts from three samples of the hepatopancreas of the poisonous scallops obtained on the Okhotsk Coast of Hokkaido Island were fractionated into two parts, hexane soluble fraction (fraction H) and 85% aqueous ethanol soluble fraction (fraction ) by partition to two layers. The majortoxic components in the mouse assay of “diarrheic shellfish toxin” by intra-peritoneal injection were found to be free unsaturated fatty acids showed the following toxicity in MU per g, 18:1 n- 35, 18:2 n- , 18: n- 167, 18:4 n- , 20: n- 167, and : n- , respectively. Toxicity of the fraction Hin MUper g was much lower than that of the fraction . However, the toxicity of the fraction H per 1 g of the hepatopancreas was about twice that of the fraction , since the fraction Hwas much more abundant than the fraction in the hepatopancreas. The method for the assay of the diarrhetic shellfish toxin must be reexamined by considering the toxic effect of the free unsaturated fatty acids.

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A structure analysis of has been carried out to determine the deuterium trap sites by neutron powder diffraction with the Rietveld profile analysis. It is revealed that the deuterium atoms are located at octahedral () sites surrounded by six Ti atoms in the crystal structure of , space group P6₃/mcm. Local vibration spectra of hydrogen in measured by neutron inelastic scattering support this result; the energy eigenvalue of the primary vibration mode is found at 7.53 kJ/mol (78 meV). The hole radius and the spring constant of the Ti-H() bond are discussed.

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L'entree en Iran des armees britannique et sovietique s'est produite en aout 1941. Elle ebranla du coup le regime de la dynastie pahlavi qui etait au pouvoir depuis 16 ans, et mena le pays vers l'instabilite politique et le chaos social. La defaite de l'arme gouvernementale, qui etait le pivot du regime de Reza Shah, reduisit considerablement le controle du gouvernement central dans le pays. Cette situation politico-sociale confuse permit le developpement de differents mouvements politiques en Iran. ainsi que le 16 aout 1942 le parti clandestin Komeley Jiyanewey Kurdistan (J-K) est ne a Mehabad, une ville au nord-ouest de l' Iran. Des sa formation, ce parti a su etendre sa sphere et, en une courte periode de temps, a fini par mettre sous son influence la ville et ses alentours. A la fin de la Seconde Guerre mondiale, en ete 1945, le J-K etait devenu une organisation representant le mouvement nationaliste kurde en Iran. a ce moment-la qu'un autre parti politique, le Hizbi Dimokratiki Kurdistan (HDK), fonde par Qazi Mihemed a Mehabad aussi, devait remplacer le J-K. Des le janvier 1946, le HDK proclama l'instauration de la≪Republique de Kurdistan≫. Cependant, les troupes sovietiques qui avaient pris sous leur protection la Republique evacuerent les terres iraniennes, en mai 1946. Six mois plus tard, sous la pression militaire du gouvernement central iranien, la republique s'ecroula. Deux theories tentent le passage du J-K au HDK. William Eagleton Jr., par exemple, affirme dans The Kurdish Republic of 1946 que le HDK a ete cree sur le conseil des autorites sovietiques. L'ex-secretaire general du Parti Democratique du Kurdistan , 'Ebd el-Rehman Qasimlu maintient par contre que Qazi Mihemed a etabli le nouveau parti de sa propre initiative, eu regard a la situation politique de cette epoque-la. Il considere que la passage du J-K au HDK comme etant l'evolution parti nationaliste clandestin en un parti democratique. En analysant ces deux theories et en se basant sur les autobiographies des personages qui se sont engages dans cet evenement, cette etude tentera le principe directeur et les activites du J-K et de mieux comprendre les raisons pour lesquelles le J-K devait etre remplace par le HDK. La conclusion generale portera sur les differents objectifs politiques du J-K et du HDK. Le J-K visait l'elevation du niveau culturel du peuple tout en luttant contre le tribalisme, qui etait, selon lui, le probleme majeur de≪la nation kurde≫, et cela en ecartant toute idee de revolte militaire. Le J-K a aussi exclu de son cadre les elites sociales telles que les leaders des tribus et dirigeants religieux de peur qu'ils n'excercent une influence sur les membres du parti. L'automne de 1944 fut le debut nouvelle ere pour le mouvement kurde. Alors que l'espoir de l'autodetermination augmentait parmi le peuple a mesure que s'approchait la fin de la guerre, la necessite de la force militaire a commence a se faire sentir dans le J-K. pour cela que s'est produite au sein du parti une tendance a compter sur l'aide militaire des sovietiques et a recourir au leadership de Qazi Mihemed, qui avait une certaine influence meme sur les leaders tribaux. Mais cette tendance etait essentiellement incompatible avec la ligne fondamentale du J-K et, graduellement, a prive ce parti de sa raison . Ainsi, le HDK se substitua au J-K en tant que≪parti democratique≫visant a rallier les elites sociales sous sa banniere, en s'appuyant sur l'autorite personnelle de Qazi Mihemed.

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1991年～2005年の福井県など4県における散発下痢症患者由来の大腸菌0153107株について, 市販の薬剤感受性ディスクを用いたKB (Kirby-Bauer) 法で12剤の薬剤感受性を調べた. 薬剤別耐性菌出現率はampicillinが72.%, streptomycinが48.%, tetracyclinおよびsulfisoxazoleが46.7%, nalidixic acid (NA) が29.%およびciprofloxacin (CPFX) が24.%などであった. 7～10剤に耐性を示す18株中16株など計26株が, NAおよびCPFXに耐性を示した. NAおよびCPFXに耐性を示した24株とNAに耐性を示した1株について, gyrAおよびparC遺伝子の解析を行った結果, 次の4typesに分けられた. type1 (1株) GyrA (SL) ・ParC (S80I), type2 (12株) GyrA (SL & 87N) ・ParC (S80I), type (株) GyrA (SL & 87N) ・ParC (S80I & G) または (S80R & V), type4 (4株) GyrA (SL & 87N) ・ParC (S80I & A108T). アミノ酸変異とfluoroquinolone (FQ) 系薬剤の最小発育阻止濃度 (MIC) との関連をみると, CPFX, ofioxacinおよびnorfloxacinのMICはtype1では, それぞれ1μg/mL, 2μg/mLおよびμg/mL, type2では～32μg/mL, ～32μg/mLおよび16～256μg/mL, type, 4では32～256μg/mL, 32～128μg/mLおよび128～>512μg/mLであった. 患者由来のFQ系剤耐性大腸菌O153が多剤耐性傾向を示すとともに, gyrAおよびparCで各々1～2カ所の変異がみられた.

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This paper applies the fuzzy cluster analysis to six international stock markets (i.., France, Germany, the U.S., Canada, Japan, and China). We analyze the similarity values calculated from the monthly stock returns, using both Zadeh's and Ward's clustering methods. These two methods induce different partition trees. Both the Minkowski distance and cophenetic correlation coefficient choose Zadeh's method over Ward's method. The optimal partition tree and the associated optimal number of clusters suggest (1) the similarity of European countries, (2) the institutional regularity of the Chinese stock market, and () the strong influence of the U.S. These implications are consistent with standard economic theory, and are preserved under the addition of three countries (i.., the U.K., Mexico, and South Korea).

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The correction factor (η_ie) for the ultimate bearing capacity of a footing placed adjacent to a slope, taking into account the combined effect of horizontal and vertical seismic loads, represented by horizontal and vertical seismic coefficients, k_h and k_v, respectively, was derived using a modified Janbu's slice method. The influence of slope angles ‘α’ on the values of ‘η_ie’ are studied here. It was found that the values of η_ie can be expressed as an exponential function of ‘k_h/(1-k_v)’ and ‘α’, with a measurable interdependency between ‘α’ and ‘η_ie’. The influence of ‘α’ on the value of ‘η_ie’ increases as the input value of ‘k_h/(1-k_v)’ increases. Equations derived based on the analytical results are proposed to account for this effect. Based on the analyses of 11 near-fault seismographers obtained in the 1999 Chi-Chi earthquake in Taiwan, a ratio between the vertical and the horizontal seismic coefficients, λ, of between ±0.25 is suggested for including the combined effect of vertical and horizontal seismic forces in evaluating the seismic bearing capacity of footings located in near-fault areas.

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At present, analytical or empirical formula for seismic bearing capacity of footings adjacent to slopes is not available. This study uses a pseudo-static-based approach in conjunction with rigorous Janbu's slice method to derive analytical values of seismic bearing capacity factors (N_γ) and correction factors for the effects of inertia of soil mass and load inclinations for a rigid footing adjacent to cohesionless slopes. It is shown that both the bearing capacity factors (N_γ) and the correction factors for the seismic bearing capacity of footings placed on level ground derived herein are comparable with those reported in the literature. Empirical equations regarding the effects of slope angles and load inclinations, expressed using generalized forms of those proposed in the literature, are also derived. It is also found that the empirical equations derived in the present study provide values of correction factors in good agreements with the analytical ones, indicating the validity of using these empirical equations for assessing the bearing capacity of rigid footings situated on the slope subjected to pseudo-static seismic loading.

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(,)-2,-エポキシ-,7,11,11-テトラメチルシクロウンデカ-,-ジエン(2)をフムレン1((2,,)-,7,11,11-テトラメチルシクロウンデカ-2,,-トリエン)より合成する既知の合成法は実際に牧率が低く合成的に問題がある.さらに,2の合成はその反応性や物性の研究のために簡単に高牧率で行われることが望まれる.今回,2の新たな合成法と簡便な精製法を見いだし,2を高牧率で1から合成することができたので報告する.1のジエポキシ化,続く再結晶により得られたジエポキシド()は二価のチタンにより還元されて,1(273%)と(25%)と少量のを含む2を主生成物(42.7%)として与えた.1とは原料として再利用できる.2の精製は1と同様硝酸銀()錯体の結晶で行い,純粋な2は1から通算牧率32.0%で得られた.2の既知方法による合成は4段階の反応と数回のカラム分離及び10%含浸シリカゲルカラム分離を必要とし牧率が極端に低い.今回,新しい2の合成法は2段階の反応で1回のカラム分離と再結晶により高い通算牧率を示す.

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【目的】ラテックス法試薬（LZテスト‘栄研’H.ピロリ抗体：栄研L，LタイプワコーH.ピロリ抗体・J：和光L）の診断精度を検討する。

【方法】検診受診者899名の血清を用い，標準である

プレート‘栄研’H.ピロリ抗体II（カットオフ U/ml：-plate）を対照に比較解析した。

【結果】内視鏡的Helicobacter pylori感染診断に基づく

-plateの感度・特異度・偽陰性率は.7%・97.0%・15.%であった。栄研Lの感度は68.%と-plateに比べ有意に低く，特異度は98.2%と同等，偽陰性率は31.%と有意に高かった。和光Lの感度は.%と同等，特異度は.%と有意に低く，偽陰性率は16.2%で同等であった。胃がんリスク層別化検査の偽A群率は，-plateの13.%に比べ，栄研Lは27.%と有意に高く，和光Lは14.4%と同等であった。

【結論】

-plateに比べ栄研Lの感度は有意に低く，偽陰性率・偽A群率は有意に高かった。和光Lは感度・偽陰性率・偽A群率のいずれも-plateと同等であった。

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BCR-ABL1 International Scale（IS）測定はチロシンキナーゼ阻害剤で治療されている慢性骨髄性白血病（CML）患者の治療効果をモニターする上で重要な検査法である。稀ではあるが，BCR-ABL1 IS測定ができないCMLが存在することが知られている。本研究において，我々は，そのようなBCR-ABL1 IS測定のできないCML患者を経験し，分子生物学的な方法で，その原因を解明した。本例ではABL1遺伝子における切断点がa2エクソン内にあることが分かり，そのことがABL1のa2エクソンを欠いた

14a（a）キメラ遺伝子のmRNAのみの発現を誘導していた。a2エクソンは本邦における検査部でのIS測定において重要な要素であり，これが欠損することが測定不能の原因であった。このようなIS測定ができない稀なCML症例をさらに集積して，その分子構造を解明することが待たれる。

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Nアルキル,4:,10-ペリレンテトラカルボン酸モノアンヒドリド=モノイミド[4a～]と芳香族アミン(アニリン,p-トルイジン,p-アニシジン,,-キシリジン,4-アミノナゾベンゼン,およびo-フェニレンジアミン)を縮合して非対称型,4:,10-ペリレンビス(ジカルボキシミド)誘導体-N-アルキル-N'-アリール-,4:,10-ペリレンビス(ジカルボキシミド)(〔a～〕,〔a～〕,〔7a～〕,〔a～〕,〔a～〕,および〔10a～〕)を合成した. これらの各誘導体はすべて赤色系の色相を示し, 顔料試験の結果N-ブチル-N'-アリール-,4:,10-ペリレンビス(ジカルボキシミド)(たとえば〔〕や〔〕)がとくにすぐれた耐光性を示した.

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