BCR-ABL

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-ABL 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-ABL 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ABL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ABL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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The possibility of attenuation of microseismic waves due to the presence of an upward folding of the ocean bottom into the liquid is discussed in this paper. The upward folding of the ocean bottom has been idealized by means of an irregularity in the form of a rectangle intruding into the liquid and the evaluation of the displacement component at any point of the solid medium has been carried out in two stages. First, the change in the incident mode of the surface wave due to the presence of the rectangular irregularity has been determined, and second, the subsequent change of the resulting displacement components due to the termination of the liquid layer and the step change in elevation of the solid medium at the continental margin has been discovered. Finally, numerical calculation has been made to determine the attenuation of the microseismic waves of different periods due to the presence of the rectangular irregularity at the ocean bottom.

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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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We screened the differentiation-inducing activities of 39 mushroom extracts from Akita prefecture, Japan, on the mouse osteoblastic cell line, MCT-. Sixteen phosphate buffered saline (PBS), 8 boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MCT- 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-,-diene-,,6β-triol (). induced ALP activities of MCT- 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- cells by , ergosterol (2), ergocalciferol (), cholesta-,,6β-triol (4), -dehydrocholesterol () and cholecalciferol (6) were tested. The enzyme activities of MCT- cells were increased .0-fold by 10 μM and 2.4-fold by 10 μM 4. However, 2, , and 6 did not induce MCT- cell ALP activity at 0.—10 μM. These results suggested that the OH groups at C- and/or C-6 of and 4 played an important role in their differentiation-inducing activities on MCT- cells. Furthermore, suppressed induction of MCT- cell apoptosis by serum starvation.

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The nucleus ¹²C was bombarded by .–MeV

3He

particles to study elastic and inelastic scattering and the (

3He

, α) reaction. Angular distributions were measured for the elastic scattering, for the inelastic scattering to levels at 4.4,

7

.6 and 9.6 MeV in ¹²C, and for the (

3He

, α) reaction to levels at 0.0, 2.0, 4.

3

(4.

7

) and 6.4 MeV in ¹¹C. The optical potential parameters were searched for to fit the

3He

elastic scattering angular distribution. The deformation parameters β₂ and

β₃

for ¹²C were determined from DWBA analysis. The angular distributions of α particles were compared with DWBA calculations and calculations including the two-step process via inelastic channel.

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The ability of Climacodon septentrionalis to immobilize and kill a mycophagous nematode (Aphelenchoides sp.) in vitro is described for the first time. Two isolates produced droplets (20–45 μm in diameter) that formed at the apices of tall, stalked, and branching secretory cells (700–

,500 μm tall). On 2% modified malt extract agar, nematodes became enveloped in the droplets, which restricted their ability to move and resulted in complete immobilization and death within several hours of contact. The rate of decomposition of the nematodes varied considerably, with most individuals persisting for weeks whereas others were degraded within several days and appeared to be colonized by dense hyphal growth. This study provides the first documentation of a non-agaricoid fungus producing secretory cells that are able to immobilize nematodes.

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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 (G

;2;;4) was performed. At first, we moved drugs from solution with pH .2 (.2±0.05) to pH .0 (.0±0.05) and measure concentration of omeprazole in solution by high-performance liquid chromatography. According to our self-developed formula, pH exposure time of resistance to PDGR for omeprazole is 4 minutes, i.. the active substance should not be released within 4 minutes at pH . 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 with the subsequent measurement of omeprazole concentration.

Results

Omeprazole concentrations after 4, 10, 15, 20, 30, 45, 60 minutes in pH

solution at the first stage were different for OO and generics. For OO, these values were 4,±0,%; 41,4±,0%; 62,8±4,0%; 79,±2,9%; ,±2,9%; 81,6±2,9%; 80,6±4,4%; for Generic - 0; 49,±9,9%; ,8 ±2,8%; 90,4±,%; , 2±2,2%; 87,±2,0%; 85,9±,%; for Generic2 - 0; 30,6±6,%; 66,±8,2%; 76,4±,4%; ,8±,%; 86,0±,%; 84,6±,%: for Generic - 80,8±,6%; ,±,9%; , 8±,2%; ,±2,%; 81,9±2,%; ,±2,0%; ,0±2,4%; for Generic4 - ,±,%; 84,4±0,8%; 84,2±,2%; , 9±0,9%; ,9±0,9%; ,9±0,9%; ,8±,%, respectively.

An analysis of the omeprazole concentration in pH

solution at the second stage revealed the following parameters after the same time: for OO - 4,4±0,6%; 40, ±,0%; 62,8±2,0%; 80,0±,%; 85,4±2,9%; ,8±,4%; 80,9±,%; for Generic - 0; 67,0±,8%; 89,±2,%; 91, 9±4,%; 89,±,6%; ,±,4%; 87,8±,2%; for Generic2 - 0; 42,2±,6%; 75,±,%; 81,0±6,0%; ,4±,2%; , 6±,%; 87,9±,0%; for Generic4 - 85,±0,%; 85,6±0,%; 84,±0,9%; ,±,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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Six full-length cDNAs encoding pig cytochrome P450 (CYP) enzymes, CYPA, CYP2A19, CYP2, CYP2C33v4, CYP2C49, and CYP2, were isolated and sequenced. The cDNA sequences of pig CYPA, CYP2A19, CYP2, CYP2C49, and CYP2 showed high similarity to human (85.4%), CYP2A13 (.6%), (81.%), CYP2C18 (85.%), and (.%), respectively, and pig CYP2C33v4 cDNA showed high similarity to rat CYP2C23 (79.2%). Reverse transcription-polymerase chain reaction (RT-PCR) assays revealed hepatic gene expression of all these pig CYP enzymes: the order of expression was CYP2C33v4 and > CYP2C49 > and CYP2A19 > . In the kidney, the CYP2C33v4 gene was expressed at the same level as in the liver, but the , CYP2A19, and genes were expressed at lower levels than in the liver. Little renal gene expression of CYP2C49 and CYP2 was observed. We revealed for the first time the full-length cDNA sequences encoding pig CYPA and five CYP enzymes belonging to the CYP2 gene family, thus making it possible to examine the gene expression levels of these CYP enzymes in pig tissues by RT-PCR.

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Choke disease fungus Epichloe typhina is associated with resistance to leaf spot disease in timothy plants (Phleum pratense). We have proposed the hypothesis that this resistance is caused by antifungal compounds existing in infected plants. We investigated the fungitoxic constituents of the stromata of . typhina. Seventy-eight compounds were isolated, including twenty novel sesquiterpenoids chokols (,2,-17,19-21,23-26), five novel oxygenated fatty acids(27-31), gamahonolide A(34) and (37), gamahorin(38) and non-fungitoxic chokorin(71) and an anthrasteroid(80). Their structures were determined by spectroscopic methods. The absolute configuration of chokol (2) was elucidated by its CD spectrum with Eu(fod)_ and a chemical correlation with epicyclonerodiol oxide(). Phytol(81), phytyl acetate() and phytyl palmitate() were identified as an inducer of aerial hyphae formation of Cladosporium herbarum. Pinoresinol(60) and diosmetin(73) were metabolized in cultures of . typhina. Pinoresinol(60) was transformed into C6 norlignan(59) and α-ribofuranoside(87). Diosmetin(73) was transformed into -O-α-ribofuranoside(). Antifungal activities of the isolated compounds were investigated.

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. 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.
. 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.
. 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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4-(2-Aminophenylthio)-, 6-dichloropyridazine (I) on treating with dil. Hydrochloric acid or acetic acid gave -chloro-H-benzo[]pyridazino[4, -][, 4]thiazine (, 4-diazapheno-thiazine type) through rearrangement and cyclization. -Chloro-10H-benzo[]pyridazino-[, 4-][, 4]thiazine (, 2-diazaphenothiazine type) was obtained by either heating of I at 150°or treating of I with conc. hydrochloric acid through direct cyclization. The mechanism of the aforesaid reactions was discussed using a molecular orbital method. Several , 2-and , 4-diazaphenothiazine derivatives were synthesized.

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The effect of composition and controlled thermomechanical process parameters on the mechanical properties of HSLA steels is modelled using the Widrow-Hoff's concept of training a neural net with feed-forward topology by applying Rumelhart's back propagation type algorithm for supervised learning, using a Petri like net structure. The data used are from laboratory experiments as well as from the published literature. The results from the neural network are found to be consistent and in good agreement with the experimented results.

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