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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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-,-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 (), -dehydrocholesterol () and cholecalciferol () were tested. The enzyme activities of MCT-1 cells were increased .0-fold by 10 μM 1 and 2.-fold by 10 μM . 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 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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Using the so-called pseudo-static method, a stability analysis was made for the mountain slide that took place at Mitake-iriya village at the time of the Izu-Ohshima-Kinkai earthquake of January 14, 1978. Undisturbed samples of volcanic clay were obtained in blocks from the exposed surface of the deposit identified to have been the sliding surface. The partially saturated clay samples were tested under consolidated undrained conditions using the triaxial test equipment. Dynamic axial stresses with irregular time histories were applied to the specimens in combination with statically sustained axial stresses to determine the soil strength under the conditions simulating in-situ states of stress during the earthquake. The results of the tests were expressed in terms of the Mohr-Coulomb type failure criterion which showed that, while the angle of internal friction remained almost unchanged, the cohesion component in irregular loading increased above values obtained in the static loading. Using the strength parameters thus determined, a pseudo-static analysis was made to check the stability of the soil masses that had actually slid during the 1978 earthquake. The maximum horizontal acceleration required to cause the slide was computed. The computed accelerations were shown to cover a range between 400 and 500 gals which is consistent with the range estimated by other investigators on the basis of overturning of tombstones in the vicinity of the slide area.

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When a mudflow moves down a slope, the gravity induced shear stress, τ, is opposed by the combined effect of the undrained shear strength, c_u, of the mud, and its viscosity, η, which is associated with the velocity gradient in the mudflow, dv/dy. In equation form this can be expressed as : τ= c_u+η(dv/dy). The resistance provided by the mud involves the contribution of both c_u and η. For an understanding of the mobilization mechanics of mudflows, one needs then these two parameters. This study describes two methods that can be used to determine these parameters. The c_u of the muds is measured using a cylinder-strength meter devise. The technique associated with this devise consists in lowering a cylinder of known dimension and weight into a mud sample, measuring the depth of penetration of the cylinder into the mud, and calculating the strength, c_u, of the mud required to support the solid cylinder at that depth. The c_u of the mud is calculated using Sokolovski's theory designed to calculate the indentation pressures developed by a Tresca plastic when a cylinder penetrates it. The determination of the viscosity, η, of the mud is obtained from either the velocity measurements of the free surface of the mudflow, or from the difference between the velocity of the free surface of the mudflow and its velocity at the interface between the mudflow and the surface on which it moves. The viscosity η is obtained from a relationship that relates these velocities with η.

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The saponin fraction from the seeds of the tea plant [Camellia sinensis (L.) O. KUNTZE (Theaceae)] was found to exhibit potent protective effects on ethanol- and indomethacin-induced gastric mucosal lesions in rats. Five new triterpene saponins, theasaponins (1), (2), (), (), and (), were isolated together with 11 known saponins from the saponin fraction. The chemical structures of 1— were elucidated on the basis of chemical and physicochemical evidence. Among the isolated saponins, theasaponins (), (), and () and assamsaponin C (10) showed an inhibitory effect on ethanol-induced gastric mucosal lesions at a dose of .0 mg/kg, p.o. and their activities were stronger than that of omeplazole. With regard to the structure–activity relationships of theasaponins, the following structural requirements for a protective effect on ethanol-induced gastric lesions were suggested; 1) the 21- and/or -acyl groups are essential for the activity, 2) acetylation of the 16-hydroxyl group reduce the activity.

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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 (700–1,500 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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Based on the assumption that an inward- or outward-directed flow perpendicular to a slope exists, this paper describes an experiment and test results. The results are compared with both traditional continuum and single-grain theories presented for the relationship between hydraulic gradient and slope angle. For the case of outward flow, the continuum theory governs the failure mechanism of the Shirasu talus deposit. The single-grain theory controls the failure process for inward flow.

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Activity-directed isolation of the ethyl acetate, methylene chloride and n-hexane fractions of Gloiopeltis furcata resulted in the isolation of 18 compounds. Their structures were elucidated as 2-(-hydroxy--oxotetrahydrofuran--yl)acetic acid (1), glutaric acid (2), succinic acid (), nicotinic acid (), ()--hydroxyhex-2-enoic acid (), cholesterol (), -hydroxycholesterol (), uridine (8), glycerol (), -(hydroxymethyl)-2-methoxybenzene-1,-diol (10), (,)--oxodeca-,-dienoic acid (11), (Z)--ethylidene--methylpyrrolidine-2,-dione (12), dehydrovomifoliol (13), loliolide (14), cholesteryl stearate (15), palmitic acid (16), cis-,8,11,14,17-eicosapentaenoic acid (17) and α-linolenic acid (18) on the basis of spectroscopic and chemical evidences. Their anticholinesterase and antioxidant activities were evaluated via inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) as well as scavenging activities on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and peroxynitrite (ONOO⁻). All isolated compounds (1—18) exhibited moderate AChE inhibitory activities with IC₅₀ values ranging from 1.14—12.50 μg/ml, whereas 1, , , 17, and 18 showed mild BChE inhibitory activities with IC₅₀ values ranging from .57—15.89 μg/ml. Although most of the compounds isolated were lacking the scavenging activity on DPPH radical and ONOO⁻, and 10 showed good DPPH radical scavenging activity, and , 10, and 16 showed potent ONOO⁻ scavenging activity.

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Alfven resonance effects on the evolution of a magnetic island driven by an externally applied perturbation are investigated for rotating plasmas. The simulation results show the importance of Alfven resonance for obtaining a perturbed current profile and estimating a critical value of the external perturbation, beyond which the magnetic island grows rapidly. The nonlinear evolution of the externally driven magnetic island is also investigated at low and high viscosities ν. It is shown that the transition phase accompanying the secondary reconnection at the initial X-point in the driven magnetic island evolution occurs in low resistivity and viscosity plasmas.

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Human papillomaviruses (HPVs) represent a family of diverse DNA viruses consisting of more than 100 types and have been extensively studied as an etiological factor in benign and malignant tumors. In malignant epithelial lesions, the mechanism by which two and proteins of the high risk HPV types, HPV 16 and 18 interact with cellular factors in deregulating the normal growth of the cells, has been well described by many authors. The and proteins are consistently expressed in HPV-associated malignant tumor and binding to the p53 gene mediated by the -associated protein ligase turned out to be important. In contrast important function of was demonstrated by its binding to pRb and Rb-related proteins. The bindings under phosphorylation of these proteins was degradated by ubiquination and transcription factors of the 2F regulated cell proliferation. Overall HPV 16 DNA is able to induced modifications in the host cells and immortalizing epithelial cells by stimulating human telomerase reverse transcriptase (hTERT) protein. High risk proteins directly interacts with c-myc and c-myc/ complex activates hTERT protein expression.
The various methods for detection or cloning of HPV DNA are summarized in this manuscript. PCR method has been become an established technique for detecting a large number of HPV DNAs. In particular PCR-RFLP is a simple and useful method for identifying the specific HPV types. However many modifications of the methods have been developed. Recently clinical trials are being conducted to test the preventive efficacy of HPV vaccines, directed against HPV 16 and 18 in Japan. In the future the therapeutic efficacy of HPV vaccines are required to prevent cervical cancer and other HPV associated cutaneous carcinomas.

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From the fronds of Polystichum tripteron (KUNZE) P_R. a new norcarotenoid glycoside was isolated and shown to be (R, , R)--hydroxy-megastigma-, -dien--one--O-β-D-glucoside. The fronds of Dennstaedtia wilfordii (MOORE) CHRIST. contain the same glucoside.

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Using two direct introduction methods, DNA synthesis or cell proliferation activities of three purified proteins from . coli, namely, human papillomavirus (HPV) proteins of type 16, a mutant type 16 (24 C-G) (transformation defective) and type b, were measured in mouse fibroblast, C127 cells. By a microinjection method, the order of the cell mitotic indexes for the three proteins as determined by -bromo-2'-deoxy-uridine (BrdU) staining was type 16, b and 16 (24 C-G). By the osmotic shock method, the

3H

-TdR incorporation and coloration by (

3

-carboxymethoxy phenyl)-2-(

4

-sulfophenyl)-2H-tetolazorium (MTS) for the three proteins correlated with the pRb binding and focus forming activities previously reported (hunger et al. 1991). These results indicate that the simple osmotic shock method for direct protein introduction may be generally useful for transformation assays of oncoproteins.

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An empirical equation in use for estimating the pseudo-elastic shear modulus, G_f, of subsoil, associated with shear strains less than 0.001% is proposed in this paper. In a series of in-situ seismic cone tests performed nationwide, the profiles of both G_f and the in-situ void ratio, , with depth were successfully characterised at five sites, each comprising a soft clay layer deposited in the Holocene era. The database which comprised the original data from the field and laboratory tests, coupled with similar information on well-documented Holocene clay deposits in Europe, was statistically analyzed in attempts to determine a generalised relationship with which G_f of soft clay may be reasonably estimated only from routinely available borehole data; that is and the current geostatic effective overburden pressure, σ'_v. An empirical relationship, G_f=, 000 -√(σ'_v) (kPa), was derived from the statistical analysis applied to data from seven different clays worldwide, for which extended over a range between 1 and , and the overconsolidation ratio ranged roughly between 1 and 2. The applicability of the proposed relationship was evaluated for two case records, each in which the clay exhibited unusual behavior; i.., the undrained shear strength remained more or less constant with depth due to the existence of artesian pressure at one site, and, at the other, G_f decreased, whereas increased, with depth. It was demonstrated that even in these clay deposits exhibiting exceptional profiles, the proposed relationship was capable of predicting G_f with a reasonable accuracy by determining the profiles of and σ'_v with depth. In addition, the prediction when compared to G_max from carefully performed laboratory cyclic tests, yielded a better estimate of G_f from the in-situ seismic survey. Despite the fact that the empirical relationship was initially designated to estimate G_f of soft clays, it may be equally applicable to sandy deposits. This was verified by comparing it to similar, and well-established, relationships developed for sands. A case record as such is also described for a loose sand deposit at Higashi-Ohgishima in Tokyo Bay which was placed in 1960's by land reclamation.

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