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 (700–1,500 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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We screened the differentiation-inducing activities of 39 mushroom extracts from Akita prefecture, Japan, on the mouse osteoblastic cell line, MC3T3-1. Sixteen phosphate buffered saline (PBS), 8 boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MC3T3-1 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-,-diene-3β,,-triol (1). 1 induced ALP activities of MC3T3-1 cells and promoted cell proliferation. To investigate the relationships between the chemical structure and differentiation-inducing activity of the compound, ALP-inducing activities of MC3T3-1 cells by 1, ergosterol (2), ergocalciferol (3), cholesta-3β,,-triol (4), -dehydrocholesterol () and cholecalciferol () were tested. The enzyme activities of MC3T3-1 cells were increased 3.0-fold by 10 μM 1 and 2.4-fold by 10 μM 4. However, 2, 3, and did not induce MC3T3-1 cell ALP activity at 0.1—10 μM. These results suggested that the OH groups at C- and/or C- of 1 and 4 played an important role in their differentiation-inducing activities on MC3T3-1 cells. Furthermore, 1 suppressed induction of MC3T3-1 cell apoptosis by serum starvation.

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背景と目的：ステロイド性骨粗鬆症は，積極的な治療介入が必要とされる．その第一選択薬はビスホスホネート製剤（以下ビス）であるが，近年，デノスマブ（以下デノス）も注目を浴びている．ステロイド性骨粗鬆症の骨密度に対する両者の効果を比較検討した．

方法：ステロイド性骨粗鬆症の管理と治療ガイドライン：2014年改訂版の薬物療法開始の基準を満たした患者を対象とした．無治療群（N群）と，治療介入群として当初よりビスで治療したBB群，ビス後デノスに変更したBD群，デノスで治療したDD群，デノス後ビスに変更したDB群を抽出し，ステロイド投与を開始した時，ステロイド性骨粗鬆症に対する治療を開始した時または薬剤変更から

カ月後の腰椎，大腿骨頚部と大転子部の骨密度を測定し，それらの変化を統計学的に比較検討した．

結果：149例が抽出され，その内訳は，N群48例，BB群24例，BD群

例，DD群21例，DB群34例であった．治療開始時または薬剤変更からカ月後にBD群を除くすべての治療介入群で腰椎の骨密度が上昇した．大腿骨の骨密度は，BD群において薬剤変更後に上昇に転じた．

考察：デノスにはビスと同様の骨密度上昇効果があると考えられた．

結論：デノスは，ステロイド性骨粗鬆症治療の第一選択薬となり得る．

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[1] The purpose of this reserch is to make clear what type of design can give good effects to win the high readership score. At the begining I had to know what factors decide the readership score, and how to change the quality of the desing into numerical value. I have used the method of multi-dimentional analysis with the help of a computer, and got the estimation formula, with kinds of factors, as follows ; A^^〜=+C+D+K+aE++cG. A^^〜=estimated values of the readership score. 1) , C, D, K : these four factors are given as category values (so we call them); each factor is classified into several categories. =week day, classified into categories. C=pages of a newspaper, which are characterized by the kinds of articles, news, and the other reading matters, classified into categories. D=kinds of goods and trades of the advertizement, classified into 14 catedories. K=constants, given to each 13 surveys. 2) , F, G : these factors are given as numerical values. G=area of advertizement, measured by the unit of column in the whole page length, being classified into kinds of area (2., 3., , , 10, 15) and 15 column means a whole page, about 2,000cm^2. , F are the marks obtained in the design of advertizements. =sum of the marks obtained in each design element on the advertizement. F=the marks obtained on the whole effect of the design. 3) a, , c : coefficients Using the above formula with the category values and the coefficients, we can obtain the naked design effect from the actual value A of readership score: aE+=A-(+C+D+K+cG). In this research, I used 1,829 data of readership score from 1960 to 1968, being obtained by 13 survevs, spring and autumn twice a year. The sample of size each survey was 3,541, 2,251, or 200 in the other 11 surveys. Multiple correlation coefficient between the estimated value A^^〜 and the actual value A is 0.951. The table 2^* shows the contribution indexes of each factor by 3 kinds of expression-(1) Range : the absolute difference between the maximum and the minimum category values, (2) Standard deviations of the category values, (3) Partial correlation coefficient : the relationship between the actual values A and each factors. *see the table 2 in the thesis in Japanese. [2] The important point was in the determination of the values of , F. is the sum of the marks obtained in each design element, classified into four kinds : =_1+_2+_3+_4. design elements [table] _1, _2, _3, _4, these values have the grades, as 0, 1, 2, 3, 4 and 0 is given to the design that has no attractive effect or no applicable element. And obtain the marks of 0 to grades as the sum of them. The values of F have also grades, 0 to 4. The principles to determine the values of , F are as follows : a) The marks obtained of , F must be the relative values among the each survey, and at the same time, they must have constancy within the same survey-the same elements of design must win the same marks obtained. ) They must be determined as to win the highest multiple correlation coefficient, when they are put into the estimation formula. c) They must be reasonable. In order to justify them, we must carry many researches on the actual condition. The frequency of accurence of each grade of , F values, as the table -4, and - in the thesis in Japanese.

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A full account is given of the chemical behavior observed for , -dialkyladeninium salts (16). On treatment with boiling 1N aqueous NaOH for 60min, 16a, , d, (X=I), 16c (X=Br), and 16f (X=ClO₄) rearranged to isomeric , -dialkyladenines (21a-f) in 50-91% yields. Treatment of the salts with 0.N aqueous Na₂CO₃ at room temperature for 30-90min or with Amberlite CG-400 (OH^-) in H₂O at room temperature gave the ring-opened derivatives a-f (in the trans-formamide form) in 56-% yields, and rate constants for the ring-opening reactions of 16a, , d-g (X=ClO₄) and 16c (X=Br) leading to a-g were determined in H₂O at pH . and ionic strength 0.50 at 25°C. Cyclization of a with NaH in AcNMe₂ at room temperature or with boiling 1N aqueous NaOH produced 21a in % or 72% yield, respectively.In solution, the trans-formamides seemed to transform slowly into the cis-formamides 23, attaining equilibria. The existence of such an equilibrium in D₂O or Me₂SO- at 25°C or in H₂O at pH . and ionic strength 0.50 at 25°C was kinetically confirmed in the case of a, and the mechanism of the rearrangement of 16 to 21 through is discussed on the basis of the above kinetic results and Deslongchamps' theory of stereoelectronic control. On treatment with NaBH₄ in MeOH at room temperature, 16a (X=I) furnished the , 8-dihydro derivative 28 (% yield), which slowly decomposed in H₂O at 60°C to give a in 49% yield.The , -dialkyladeninium salts (16) were found to be obtainable from N'-alkoxy-1-alkyl--formamidoimidazole-4-carboxamidines () through an alternative synthetic route : Alkylations of with alkyl halides in HCONMe₂ in the absence of base, followed by hydrogenolysis of the N'-alkoxy group and cyclizatio (or vice versa) produced 16 in acceptable yields. In order to interpret the proton nuclear magnetic resonance spectrum of a, the 2-deuterated species 26 was also synthesized from 24 via 25 and 27.

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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 % 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- , 18:3 n-3 167, 18:4 n-3 , 20: n-3 167, and : n-3 , 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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The gamma-ray spectrum and the conversion-electron spectrum are measured in the decay of the Tb¹⁵² activity. The L-subshell electron lines of the 586. keV +→2₁⁺ transition are separated by the ion-free beta-ray spectrometer. The M1-2 mixing ratio, δ², and the dimensionless ratio X of 0-2 mixing of the 586. keV transition are obtained to be δ²≤0.16 and 0.034≤X≤0.038, respectively. The 2 branching ratio (2; +→0_g⁺): (2; +→2₁⁺): (2; +→0₁⁺) is determined to be 0.023 : 1.0 : ..

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The gamma-ray spectrum and the conversion-electron spectrum are measured in the decay of the ^116mIn activity. Directional correlations are also measured for 818–1293 and 1097–1293 keV cascades. The M1-2 mixing ratio δ, and the 0-2 mixing ratio μ_k are obtained for 818. keV +→2₁⁺ transition to be δ=1.52−

0.22

+0.26, and μ_k≤

6

.1×10⁻⁴ respectively. The

E

2 branching ratio

B

(

E

2;

2₂

+→0_g⁺):

B

(

E

2;

2₂

+→2₁⁺):

B

(

E

2;

2₂

+→0₁⁺) is determined to be 0.0158:1.0:

5

.86.

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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;3;4) was performed. At first, we moved drugs from solution with pH 1.2 (1.2±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±3,0%; 62,8±4,0%; 79,±2,%; ,±2,%; 81,±2,%; 80,±4,4%; for Generic1 - 0; 49,3±,%; 88,8 ±2,8%; 90,4±3,%; 88, 2±2,2%; 87,3±2,0%; ,±1,1%; for Generic2 - 0; 30,±,3%; 66,±8,2%; 76,4±,4%; 82,8±,3%; 86,0±3,%; ,±3,3%: for Generic3 - 80,8±3,%; ,±1,%; , 8±3,2%; ,3±2,%; 81,±2,1%; 82,1±2,0%; 82,0±2,4%; for Generic4 - 82,±1,%; ,4±0,8%; ,2±1,2%; 82, ±0,%; 82,±0,%; 82,±0,%; 82,8±1,1%, 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,%; 40, ±3,0%; 62,8±2,0%; 80,0±3,1%; ,4±2,%; 82,8±3,4%; 80,±3,%; for Generic1 - 0; 67,0±,8%; 89,±2,3%; 91, ±4,3%; 89,1±1,%; 88,3±1,4%; 87,8±1,2%; for Generic2 - 0; 42,2±,%; 75,1±,3%; 81,0±,0%; 88,4±3,2%; 88, ±1,3%; 87,±1,0%; for Generic4 - ,±0,%; ,±0,%; ,±0,%; 82,±3,0%; ,4±0,3%; ,4±0,3%; ,3±0,4%, respectively. Generic3 release and degradation were completely realized at pH 4.

Conclusion

Decreased gastric stability of Generic3 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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Some existing analytical methods which have been used in geotechnical engineering are modified to handle the shear strength reduction with time due to softening in fissured, over-consolidated clays and mudstones. These are limit equilibrium analysis of slope stability, calculation of earth pressure and calculation of stress and displacement around a tunnel. The softening effect is incorporated in these analyses using the failure criterion and the time-dependent strength parameters proposed previously by the authors. Examples are presented which emphasize the importance of appreciating the softening effect in analyses and further illustrate that the effect of shear strength reduction with time due to softening could easily be captured with existing analytical methods.

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Brassinolide analogues, (R, 23R, 24R)-2α, 3α, , 23-tetrahydroxy--homo--oxa--ergostan--one (24-epibrassinolide) (10) and (S, 23S, 24R)-2α, 3α, , 23-tetrahydroxy--homo--oxa--ergostan--one (), were synthesized from brassicasterol (3a) in five steps and with ca. 20% overall yield. The key steps are the direct formation of (, 24R)-3α, -cyclo--ergost--en--one (4) from brassicasterol mesylate (3), the acid-catalyzed rearrangement of 4 to (, 24R)--ergosta-2, -dien--one (), and the Baeyer-Villiger oxidation of the tetrahydroxy -ergostan--ones and 8.

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