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-,,-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-,,-triol (4), 7-dehydrocholesterol () and cholecalciferol () 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, , and did not induce MCT-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 MCT-1 cells. Furthermore, 1 suppressed induction of MCT-1 cell apoptosis by serum starvation.

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This paper outlines a mathematical description of the stress dilatancy behaviour of granular materials which accounts for stress level and void ratio dependencies. The consideration of these aspects has important implications in the modelling of granular material behaviour. In fact, granular material mechanical response is largely dominated by the evolution of dilatancy, fabric and void ratio histories. The starting point in this study is the well established Rowe's theory which is revisited and ultimately modified by introducing a factor linked to governing state parameters in order to describe the complete behaviour of granular materials during deformation. Numerical simulations of triaxial tests on granular materials at different void ratios and stress levels are herein presented to illustrate the model.

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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, -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-, -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 , 7-dienes were irradiated and the corresponding vitamin 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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乳牛の分娩性起立不能症予防のための基礎的資料を得る目的で、分娩後2日以内に起立不能に陥ったホルスタイン種乳牛例の血漿25(OH)濃度を調査した。初診日の血漿25(OH)濃度は、15.0～174.(58.±40.,M±SD)ng/mlと個体間の差が大きく、また、分娩前におけるV-剤の経口投与の有無により差異が認められた。すなわちV-剤投与牛(n=10)では88.7±40.ng/mlであり、非投与牛(n=12)の30.±7.0ng/mlに比べ、有意(P＜0.01)な高値を示した。初診後の経過にともない25(OH)濃度は、ほとんど変化がみられなかった。

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Two new vitamin analogues, 1α-hydroxy-24, 24-dimethyl--dehydrovitamin (13) and 1α, 25-dihydroxy-24, 24-dimethyl--dehydrovitamin (17), which are blocked for 24-hydroxylation by the methyl groups, were synthesized from 1α, -bismethoxymethoxypregn--ene-20Scarbaldehyde () by using the orthoester Claisen rearrangement for construction of the carbon skeleton of their side chains. These compounds (13 and 17) elicited a rise in serum calcium, but not in serum inorganic phosphorus in rats. In a bioassay for alkaline phosphatase, they were found to show much weaker activity than 1α-hydroxy vitamin ().

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Three objects are A, B and C. The ship's positon is P. This is the instrument by which the ship's course will be recorded on the chart, if one on board is moving index mirror so that image A may be on B through telescope on sextant and the other is moving another sextant so that image C may be on A. Figure 1 shows the principle of this instrument except sextant, where is the point which AB^2=AC・. Take Q and such that AB^2=AP・AQ, AB=. then follows ∠ABQ=∠APB, ∠ADQ=∠APC. Fig.2 shows the outline of this instrument put on paper except sextant. Fig., 4, , are in detail of fig.2. Fig.7 shows the sextant with synchromotor, (12) shows the cover of syncromotor. Fig.8, shows the part of instrument which must be reformed next time.

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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 7 kinds of factors, as follows ; A^^〜=B+C++K++bF+cG. A^^〜=estimated values of the readership score. 1) B, C, , K : these four factors are given as category values (so we call them); each factor is classified into several categories. B=week day, classified into 7 categories. C=pages of a newspaper, which are characterized by the kinds of articles, news, and the other reading matters, classified into categories. =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., ., , 7, 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. ) a, b, 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: +bF=A-(B+C++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 ,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 kinds of expression-(1) Range : the absolute difference between the maximum and the minimum category values, (2) Standard deviations of the category values, () 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+_+_4. design elements [table] _1, _2, _, _4, these values have the grades, as 0, 1, 2, , 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. b) 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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Callipeltin A (1) is a cyclodepsipeptide from water sponge collected at New Caledonia. This compound shows anti-HIV and cytotoxic activities against KB and P388 cells and contains three new amino acid residues. β-methoxytyrosine (β-MeOTyr) (4), (2R,R,4S)-4-amino-7-guanidino-2,--dihydroxyheptanoic acid (AGDHE) (), (S,4R)-,4-dimethyl-L-glutamine (diMeGln) (). In addition, two new truncated open-chain derivatives of Callipeltin A (1), named Callipeltin (2) and () were isolated. The unique structure and intriguing biological activities of this compound led us to explore total synthesis of Callipeltin A (1) and to elucidate stereochemistry of β-MeOTyr (4). We started to synthesize Callipeltin () which contains β-MeOTyr (4). In order to synthesize four stereoisomer of β-MeOTyr (4), we attempted Evans anti or syn-Aldol reaction as a key step. Evans direct anti-aldol reaction with chiral benzyloxazolidinones (8) and p-hydroxy benzaldehyde () promoted by catalytic amounts of MgCl_2 in the presence of triethylamine and chlorotrimethylsilane. This proceder provide :1 diastereoselelctivity and 70% yield of isolated anti-aldol product (10). And Enolizalion of isocyanate oxazolidinone (13) with di-n-butylboryl trifrate and diisopropylethylamine followed by treatment with aldehyde 8 afford syn-aldol product 14 affording 88% yield and 1: anti: sin diastereomeric ratio. On the other hand, we tried Sharpless Asymmetric dihydroxylation () and Aminohydroxylation (AA) to give all four stereoisomers of β-MeOTyr. Treatment of olefin (18) with -mix α provided diol (19) and the α position alcohol of 19 was converted to sulfone regioselectively followed by azidation and treatment of 20 with PPh_ to afford aziridine (21). Addition of aziridine (21) and BF_・Et_2O in methanol produced α-amino β-methoxy adduct (). AA reaction protocol with t-butylcarbamate was successfully applied to afford desired in single step. Now we construct Callipeltin to determine absolute stereochemistry of β-MeOTyr (4). In addition, we report the synthesis of diMeGln () and (2R,R,4S)--hydroxy-2-4--trimethyl hepanoic acid (7).

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Amyloid β (Aβ) plays a key role in the pathology of Alzheimer’s disease (

) and is toxic owing to its ability to aggregate into oligomers and fibrils. Aβ has high aggregative ability and potent toxicity due to the “toxic turn” at positions and 23. Furthermore, APP knock-in mice producing P-Aβ with the toxic turn exhibited -related phenotypes such as cognitive impairment, Aβ plaque accumulation, and tau hyperphosphorylation. In these mice, it is suggested that the activation of neuroinflammation and dysregulation of hypoxia-inducible factor (HIF) expression in the hippocampus contribute to the pathogenesis of -related phenotype. However, it remains unclear which cells are responsible for the dysregulation of HIF expression and the neuroinflammation which was induced by P-Aβ with the toxic turn. Here, we investigated the effects of chronic treatment with P-Aβ42 and lipopolysaccharides (LPS) on the inflammatory response in BV-2 microglia. Chronic treatment with P-Aβ42 and LPS increased nitric oxide production and the expression of interleukin- (IL-), whereas it reduced the expression of HIF-1α and HIF-α in BV-2 microglia. The reduction of HIF-1α caused by P-Aβ42 and LPS was milder than that caused by LPS. Furthermore, chronic treatment with P-Aβ42 and LPS increased the nuclear translocation of nuclear factor-kappaB (NF-κB). P-Aβ42 could enhance the inflammatory response of microglia with abnormal HIF signaling and contribute to the progression of pathology.

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Agaricus blazei is an important fungus for producing bioactive compounds. There are some reports of polysaccharides and steroid derivatives from the fruiting bodies of A. blazei. However, the chemical examination of the secondary metabolites of the cultured mycelia of this species has not been reported. Eight compounds, an unprecedented skeleton have been isolated from the cultured mycelia of A. blazei. The structures of the novel compounds each named blazeispirols A (1), B (2), C (), (4), () X(), Y (7) and Z (8) were confirmed by extensive 1 and 2 NMR spectral data and X-ray analysis. Blazeispirols A (1), B (2), C (), (4) and () were des-A-ergostane type compounds having spiroacetal structure as a side chain. Blazeispirols X () and Y (7) were determined to be (20S, S, 23R, 24S)-1 (10→) abeo-14β, :, 25-diepoxyergosta-,7,,11-tetraene-α,23-diol and (20S, S, 23R, 24S)-14β,:,25-diepoxy-,23-dihydroxyergosta-4,7,11-triene-,-dione by comparison of extensive 1 and 2 NMR spectral data with that of blazeispirol A. The biosynthesis of blazeispirol A was investigated by feeding ^<13>C-labeled acetates and methionine to the growing cultures of A. blazei. The labeling patterns of 1 derived from singly and doubly ^<13>C-labeled acetates were consistent with that of ergosterol reported previously except for the A-ring and then ^<14>C-labeled ergosterol was incorporated into blazeispirol A. Taking the structures of blazeispirols Z and into consideration, it can be assumed that blazeispirol A is biosynthesized from ergosterol by the cleavage of C-4, C- and C-1, C-10 bonds on retro aldol condensation and Michael reaction via such as intermediate A as shown in Fig. 4. A large number of ergostane-type steroids have been isolated from many fungi. However, blazeispirol A is the first example of a naturally occurring des-A-ergostane-type steroid including a spiroacetal structure moiety as a side chain.

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We purified a sterol with antitumor activity from the edible mushroom Sarcodon aspratus (BERK.) S. ITO and identified it as ,8α-epidioxy--ergosta-,(11),-trien--ol (,11-dehydroergosterol peroxide ((11)-DHEP)). Purified (11)-DHEP was a more effective inhibitor of HL60 leukemia cell growth and stronger apoptosis-inducer than ,8α-epidioxy--ergosta-,-dien--ol (ergosterol peroxide (EP)) that we had previously identified as an apoptosis inducer. Moreover, (11)-DHEP selectively suppressed the growth of HT29 human colon adenocarcinoma cells but not WI38 normal human fibroblasts. After incubation of HT29 with 7 μM (11)-DHEP, the number of S phase cells decreased from 23 to 15% of total diploid cells and 17% became hypodiploid. Expression of the cyclin-dependent kinase inhibitor 1A (p21, WAF1, Cip1) (CDKN1A), which has been shown to cause cell cycle arrest and apoptosis in HT29 cells, was induced by (11)-DHEP. These results suggest that (11)-DHEP inhibits HT29 cell growth by inducing CDKN1A expression, thus causing cell cycle arrest and apoptosis.

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Eight new sterols, , 8α-epidioxy-(, 24R)-23-methylergosta-, -dien--ol (1), , , -trihydroxy-(, 24R)-23-methylergosta-7, -dien--one (2), , , -trihydroxy-(24S)-ergost-7-en--one (), , , , 14α-tetrahydroxy-(, 24R)-ergosta-7, -dien--one (4), (, 24R)-ergosta-7, -diene-, , , -tetrol (), , -epidioxy--hydroxy-(, 24R)-ergosta-7, -dien--one (), , -epidioxy--hydroxy-(24S)-ergost-7-en--one (7) and , -epoxy-(, 24R)-ergosta-8, -diene-, 7β, 14α-triol (8), have been isolated from five edible mushrooms, Lentinus edodes, Flammulina velutipes, Hypsizigus marmoreus, Pleurotus ostreatus and Pholiota nameko together with fifteen known ones (-23), of which two (16 and 17) are reported for the first time from a fungal source. The structures of these new compounds were elucidated on the basis of their spectral data.

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Two new steroid derivatives, (, 24R)--ureido-ergosta-4, , 8(14), -tetraene (1) and (, 24R)-, 8α-epidioxyergosta-, , -triene--ol -O-β--glucopyranoside (2) were isolated from the fruit bodies of Chlorophyllum molybdites (Agaricaceae). The structures were established by spectroscopic and chemical methods. These compounds exhibited cytotoxicity against Kato III cells.

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Six new sterols, , ;8α, -diepoxy-(, 24R)-ergost--ene-, 7α-diol (1), , ;8α, -diepoxy-(, 24R)-ergost--ene-, 7β-diol (2), , -epoxy-(, 24R)-ergosta-8, -diene-, 7β-diol (), (, 24R)-23-methylergosta-7, -diene-, , -triol (4), (, 24R)-23-methulergosta-7, -diene-, , , -tetrol () and (24S)-ergost-7-ene-, , , -tetrol (), have been isolated from seven mushrooms, Amanita pantherina, Amantia virgineoides, Lactarius piperatus, Lyophyllum shimeji, Tricholoma portentosum, Hypsizigus marmoreus and Lentinula edodes together with eighteen known ones (7-24). The structures of these new compounds were elucidated on the basis of their spectral data.

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In the first part of the present work the interaction of glycophorin with dimyristoylphosphatidylcholine (DMPC) is studied by freeze fracture electron microscopy, densitometry, calorimetry, and 90° static light scattering. An exothermic lipid/protein interaction energy of W_P=190 kJ•mol^-1 was found by application of the well known Van Laar relation for the displacement of the freezing point and the Gibbs-Duhem relationship. Secondly, the effects of Ca²⁺ on the lipid/protein interaction were studied. Following Ca²⁺ addition a remarkable decoupling of the interaction of the glycophorin head group with the bilayer surface was revealed by densitometry and gold-labeling electron microscopy. It is estimated that about 80% of lipid once disturbed by the adsorption of glycophorin head groups is decoupled after addition of Ca²⁺. Thirdly, the selective interaction of glycophorin with binary lipid mixtures was studied, including the mixtures of DMPC with dimyristoylphosphatidylserine (DMPS) and dilauroylphosphatidylcholine (DLPC), and the mixture of dipalmitoylphosphatidylcholine (DPPC) with DLPC.

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A new analytical method is proposed for determining the inextensible grid reinforcement pullout resistance and pullout force/pullout displacement curve by using basic backfill soil and grid reinforcement properties. The pullout skin friction resistance/pullout displacement relationship is simulated by linear elastic-perfectly plastic model. A hyperbolic model has been proposed to represent the pullout bearing resistance/pullout displacement relationship in which the maximum bearing resistance of a single bearing member is determined using a new bearing capacity equation proposed in this paper. The influences of the grid bearing member spacing ratio, S/, the bearing member deflection rigidity, and the pullout softening behavior on the mobilization of pullout bearing resistance are explicitly included in the proposed model. Good agreement has been obtained between calculated values and laboratory test results.

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