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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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-6 , 18: n- 167, 18:4 n- , 20:5 n- 167, and :6 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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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. C'est 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 d'activite 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. C'est 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 d'expliquer 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 d'Iran, '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 d'un 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 d'examiner 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 d'une 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. C'est 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 d'etre. Ainsi, le HDK se substitua au J-K en tant que≪parti democratique≫visant a rallier d'abord les elites sociales sous sa banniere, en s'appuyant sur l'autorite personnelle de Qazi Mihemed.

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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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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 c) 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.
5. 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.
6. 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
c) 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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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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We screened the differentiation-inducing activities of 39 mushroom extracts from Akita prefecture, Japan, on the mouse osteoblastic cell line, MCT-1. Sixteen phosphate buffered saline (PBS), 8 boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MCT-1 cell differentiation. The enzyme activities were markedly induced by extracts of Tricholoma auratum, and we isolated the active compound from methanol extracts of this mushroom. Physical data for the isolated active compound were identical to those for (,24R)-ergosta-7,-diene-,5α,6β-triol (1). 1 induced ALP activities of MCT-1 cells and promoted cell proliferation. To investigate the relationships between the chemical structure and differentiation-inducing activity of the compound, ALP-inducing activities of MCT-1 cells by 1, ergosterol (2), ergocalciferol (), cholesta-,5α,6β-triol (4), 7-dehydrocholesterol (5) and cholecalciferol (6) were tested. The enzyme activities of MCT-1 cells were increased .0-fold by 10 μM 1 and 2.4-fold by 10 μM 4. However, 2, , 5 and 6 did not induce MCT-1 cell ALP activity at 0.1—10 μM. These results suggested that the OH groups at C-5 and/or C-6 of 1 and 4 played an important role in their differentiation-inducing activities on MCT-1 cells. Furthermore, 1 suppressed induction of MCT-1 cell apoptosis by serum starvation.

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The association between apolipoprotein (Apo-) polymorphism and the response of plasma cholesterol to dietary therapy (cholesterol intake of less than 300mg/day) was investigated for about 8 weeks in 208 nonfamilial hypercholesterolemia patients (/ 161, 4/ 47). The baseline lipoprotein concentration and the intake of energy and lipids were not significantly different between subjects with / and those with 4/ phenotypes. After the dietary therapy plasma total cholesterol and low density lipoprotein cholesterol were significantly decreased in both phenotype groups (p<0.05). The patients with 4/ had significantly smaller reductions of LDL-C than the patients with /. The changes of LDL-C showed a significant difference between the patients with / and 4/ by the Kruskal Wallis test (p=0.041). The presence of 4/ predicted the degree of cholesterol reduction following dietary therapy.

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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48.6%, 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 & DN) ・ParC (S80I), type (8株) GyrA (SL & DN) ・ParC (S80I & 84G) または (S80R & 84V), type4 (4株) GyrA (SL & DN) ・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8μg/mL, type2では8～32μg/mL, 8～32μg/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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Chemical synthesis of (, 24R)- and (, 24S)-1, 24-dihydroxy--vitamin has been achieved starting with the commercially available dinorcholenic acid acetate. Synthesis involved introduction of the 1-hydroxy group by a reduction of the 1, 2-epoxide generated by epoxidation of the 1, 4, 6-trien--one. The side chain on the steroid was then constructed by means of a Wittig reaction followed by introduction of the Δ⁷ bond by standard methods and its protection with 1-phenyl-1, 2, 4-triazoline-, 5-dione. Subsequent reduction of the hydroxy groups in the steroid side chain followed by reduction of the Diels-Alder addition products yielded the both 24-isomers. The 5, 7-dienes were irradiated and the corresponding vitamin D compounds isolated. Nuclear magnetic resonance was used to identify individual isomers. The (, 24S)-1, 24-hydroxyvitamin compound bound equally well to the chick intestinal cytosol receptor as 1, 25-dihydroxyvitamin , while the 24R-isomer was approximately ten times less active. In vivo, both isomers were less active than 1, 25-dihydroxyvitamin ; however, the 24S-isomer was considerably more active than the 24R-isomer approaching the activity of 1, 25-dihydroxyvitamin .

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(6,)-2,-エポキシ-,7,11,11-テトラメチルシクロウンデカ-6,-ジエン(2)をフムレン1((2,6,)-,7,11,11-テトラメチルシクロウンデカ-2,6,-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(8)は二価のチタンにより還元されて,1(273%)と8(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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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%; 62,8±4,0%; 79,5±2,%; ,5±2,%; 81,6±2,%; 80,6±4,4%; for Generic1 - 0; 49,±,%; 88,8 ±2,8%; 90,4±,7%; 88, 2±2,2%; ,±2,0%; 85,±1,1%; for Generic2 - 0; 30,6±6,%; 66,7±8,2%; 76,4±7,4%; ,8±5,%; 86,0±,7%; 84,6±,%: for Generic - 80,8±,6%; ,5±1,%; , 8±,2%; ,±2,7%; 81,±2,1%; ,1±2,0%; ,0±2,4%; for Generic4 - ,5±1,7%; 84,4±0,8%; 84,2±1,2%; , ±0,%; ,±0,%; ,±0,%; ,8±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±0,6%; 40, 5±

,0%; 62,8±2,0%; 80,0±,1%; 85,4±2,%; ,8±,4%; 80,±,5%; for Generic1 - 0; 67,0±7,8%; 89,7±2,%; 91, ±4,%; 89,1±1,6%; 88,±1,4%; ,8±1,2%; for Generic2 - 0; 42,2±5,6%; 75,1±7,%; 81,0±6,0%; 88,4±,2%; 88, 6±1,%; ,±1,0%; for Generic4 - 85,5±0,5%; 85,6±0,5%; 84,7±0,%; ,7±,0%; 84,4±0,%; 84,4±0,%; 84,±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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本検討は, 経皮的冠動脈形成術 (PCI) 後の翌日血液透析 (HD) 時における透析中低血圧 (IDH) の発生因子について検討した. 対象は待機的PCI後, 翌日HDを施行した慢性HD患者連続

名 (年齢70±7歳, 男性64名). IDHの定義は, 収縮期血圧20mmHg以上の低下で, 症状を伴いかつHD中断を要したものとした. また, HD記録よりIDHを後方視的に調査し, Logistic回帰分析にてIDHの予測因子を検討した. IDH群 (12名) は非IDH群 (71名) に比して, 有意に低体重 (52.0±.8 vs. 62.±1.5kg; p=0.007), 造影剤量/体重が多く (2.5±0. vs. 1.8±0.1mL/kg; p=0.018), 低左室駆出率で (45.8±4.2 vs. 56.0±1.8% ; p=0.030), /’ が高値 (.±.8 vs. 17.2±0.cm/sec; p=0.038) であった. また, 冠動脈病変や侵襲的な治療について有意差は認めなかった. Logistic回帰分析では, 造影剤量/体重 (OR, 6.; 95%CI, 1.-25.8; p=0.004) がIDHの有意な予測因子であった. 造影剤使用量が多い症例は, IDHを生じる危険性が高いことが示唆された.

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