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大学学部の教育カリキュラムにおいて、フィールドワーク科目と講義科目・ゼミ・卒業論文の関係をどのように効果的に構成するか。それは各大学や学部・学科の教育方針によって異なるであろう。本稿では、筆者のインド・フィールドワーク科目の実践を手掛かりに、所属する学科の3・4年次ゼミと卒業論文との関係を検討した。過去10年間でインド・フィールドワークとゼミとの関係は、現代インドについて理解するという方向性から、インドと他国を比較して考えるという方向性にシフトしてきた。その結果、インド・フィールドワーク経験者は3・4年次ゼミ選択において国際関係論以外のゼミ（社会福祉学等）を選ぶ機会が増大した。卒論テーマの選択も、インド以外の内容が増加した。こうした変化はインド・フィールドワークの教育効果の低下を意味するのではなく、学生の国際比較の理解力（インドと他国を比較考察しようとする感性）の高まりとして解釈しうる。大学における海外フィールドワーク科目の役割や方向性は、特定地域の理解を重視するものだけでなく、国際比較の視座を重視するものを含めて多元的であると考えられる。, How should the relationship between fieldwork courses and other courses such as lecture, seminar, and graduation thesis courses be coordinated in the curricula of undergraduate programs ? It depends on the academic policies of universities and departments. This paper reviews the author’s education practices in fieldwork in India and the relationship between fieldwork and junior/senior seminar. In the last 10 years, this relationship has changed from the understanding of modern India to comparative perspectives of India and other countries, which provide the students with greater opportunities to choose seminars of various disciplines (social welfare, etc.) as well as international relations seminars. The students who participated in fieldwork in India preferred writing their graduation theses on the case study of countries other than India. This tendency should be analyzed not as a decrease of the educational effect of fieldwork but as an increase of the comparative understanding of India and other countries. It can be said that the educational roles and orientations of international fieldwork in university curricula are plural. The educational emphasis of fieldwork courses can be on understanding specific areas as well as creating a comparative perspective of certain topics.

Nanoparticle albumin-bound (nab)-paclitaxel is a 130-nm formulation containing human serum albumin (HSA). The clinical efficacy of this formulation is considered to depend on its affinity for HSA. The high pressure employed during the manufacture of nab-paclitaxel HSA (nab HSA) may influence its conformation and/or oligomerization, and ultimately its affinity for HSA. Therefore, studies are required to evaluate whether the affinity of paclitaxel for nab HSA is similar to that of generic HSA (control HSA). In the present study, nab HSA was isolated from nab-paclitaxel by gel filtration, and the binding affinities (K(D)s) were determined by surface plasmon resonance. Furthermore, the affinity of docetaxel for nab HSA and control HSA was measured, as their binding sites are similar. Paclitaxel showed K(D)s of 8.93±8.60 and 7.39±5.81 µM for nab HSA and control HSA, respectively, whereas the corresponding K(D)s for docetaxel were 44.3±9.50 and 55.9±2.28 µM, respectively. This suggests that the paclitaxel binding site was not modified during the nab-paclitaxel manufacturing process. Additionally, nab HSA likely does not affect paclitaxel and blood HSA binding, as evidenced by the similar affinities of paclitaxel and docetaxel for nab HSA and control HSA. In conclusion, the binding affinities of paclitaxel and docetaxel for nab HSA and control HSA were found to be comparable. Additionally, the manufacturing process did not influence the paclitaxel binding affinity for nab HSA. These results also suggest that nab HSA may not affect the clinical effectiveness of nab-paclitaxel.

2016年3月、チベット亡命政府 (CTA) の長である主席大臣 (Sikyong) が、有権者による直接投票で選出された。現在、チベット亡命政府は民主主義体制の構築に力を入れているが、はたして民主化はどの程度進んでいるのか。本稿では、近年実施された選挙の各種データを用いて、世界各地に離散して暮らしているチベット人の投票行動を考察し、チベット亡命政府の民主化の進展をポリアーキーの概念（異議申し立てと参加の包括性）に準拠しながら検討する。本論では次の作業仮説を立てる。亡命チベット人は離散しているがゆえに、有権者が得られる選挙情報（選挙公約、経歴、人柄、政党、支援団体など）は居住地によって分断されており、投票行動は居住地によって差異が生じるだろう。特に、候補者の情報が乏しい場合、有権者は地縁等に基づいた投票行動をとりやすくなるのではないか。第2節では、チベット亡命政府のこれまでの民主化改革の動向を整理する。第3節では、2015-2016年の亡命チベット代表者議会選挙および主席大臣選挙が、どのような結果であったのかを、選挙結果データを用いて分析する。当選した議員の属性、世界各地の投票所単位の集計結果などの関連性を探る。そして、亡命チベット人有権者の投票行動の特徴を明らかにしようと試みる。選挙期間中の候補者陣営の動向や投票結果のデータから読み取れるのは、地縁、学歴、その他の様々な要因が複雑に絡み合って、亡命チベット人の投票行動を左右しているという点であった。有権者の地縁のつながりに着目して、ウ・ツァン地区出身者の地域組合を利用しようとする動きがみられた。また、候補者の学歴を投票の評価基準にしている傾向が北米の事例で考察された。亡命チベット人有権者は、様々な思惑で投票しており、亡命チベット政府は異議申し立ての自由の保障に一定程度まで成功してきていると考えられる。, Tibetans in Exile have exercised their votes on the election of President (Sikyong) of the Central Tibetan Administration (CTA) in March, 2016. Tibetan Governments in Exile have made progress in building their democratic institutions. This paper analyzes the CTA's democratization process by using the recent elections data, especially on the aspects of Tibet diaspora's voting behaviors around the world from viewpoints of voters' contestation and inclusiveness, which are theorized in the notion of "polyarchy"Tentative hypothesis of this paper is as follows; in case of Tibetan diaspora who lives in remote areas, the opportunities to get election news such as manifesto, candidates' careers, and party politics are limited so that their vote behaviors depend on the characteristics of their residential areas. Regional sentiments will have a big impact on their voting preferences. Section Ⅱ shows the past democratization process which CTA had been engaged in. Section Ⅲ analyzes the election results of President and members of Parliament in Exile 2015-16 by using statistic data, focusing on the correlation between the elected candidates and the poll stations. These observations will lead to figure out the uniqueness of Tibetan in Exile's voting behavior. It is argued that regional sentiments of the voters, the educational careers of the candidates, and the other factors have strong relation with the voting preferences. The voters who have roots in U-Tsang province had been major political targets of mobilization based on their regional sentiments. The voters who live in North America tend to prefer candidates with higher educational backgrounds. It is reasonable to say that CTA has succeeded in protecting the voters' freedom of contestation to a certain extent.

We herein report a case of hemichorea-hemiballism in an 85-year-old man diagnosed with diabetes at 76 years of age. After a one-year interruption in treatment, he was treated with a low-calorie diet, linagliptin, and nateglinide. Over 51 days, his HbA1c level decreased from 15.8% to 7.7%. After a prompt improvement in his hyperglycemia, he began experiencing involuntary movements in the right upper and lower extremities. T1-weighted magnetic resonance imaging showed a high signal intensity in the left lens nucleus. The patient was diagnosed with diabetic hemichorea-hemiballism and received haloperidol (1 mg/day) as treatment.

Herein, we report on an 82-year-old woman who presented with anorexia. The patient had hyponatremia with preserved urinary osmotic pressure. T1-weighted magnetic resonance imaging (MRI) showed a lack of high signal intensity (SI) in the posterior pituitary lobe. Based on the patient's high levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), heart failure was suspected. The heart failure may have caused arginine vasopressin (AVP) secretion. The depletion of AVP secretory granules may therefore cause the posterior pituitary gland to disappear on T1-weighted MRI.

Osteoarthritis (OA) is a degenerative disease characterized by joint destruction and loss of cartilage. There are many unmet needs in the treatment of OA and there are few promising candidates for disease-modifying OA drugs, particularly, anabolic agents. Here, we describe the identification of novel quinazolin-4(3 H)-one derivatives, which stimulate chondrocyte cartilage matrix production via TRPV4 and mitigate damaged articular cartilage. We successfully identified the water-soluble, highly potent quinazolin-4(3 H)-one derivative 36 and studied its intra-articular physicochemical profile to use in in vivo surgical OA model studies. Compound 36·HCl provided relief from OA damage in a rat medial meniscal tear (MT) model. Specifically, 36·HCl dose-dependently suppressed cartilage degradation and enhanced the messenger RNA expression of aggrecan and SOX9 in cartilage isolated from MT-operated rat knees compared with knees treated with vehicle. These results suggest that 36 induces anabolic changes in articular cartilage and consequently reduces OA progression.

Four wethers were used in a 4 × 4 Latin square design experiment to evaluate in vivo digestibility of total mixed ration (TMR) silage with food by-products for dairy cows, and the ruminal condition and nitrogen (N) balance were examined. Five by-products (i.e. potato waste, noodle waste, soybean curd residue, soy sauce cake and green tea waste) were obtained. Four types of TMR silage were used: control (C) containing roughage and commercial concentrate, T1:20% and T1:40% containing the five by-products replacing 20% and 40% of the commercial concentrate on a dry matter (DM) basis, respectively, and T2:40% containing three by-products (potato waste, noodle waste and soybean curd residue) replacing 40% of the commercial concentrate on a DM basis. The ingredients were mixed and preserved in oil drum silos for 4 months. The TMR silages showed 4.02–4.44% and 1.75–2.19% for pH and lactic acid contents, respectively. The digestibility of DM and neutral detergent fiber, and total digestible nutrient content were higher (P

Acidification of the glycoprotein, miraculin (MCL), induces sweet taste in humans, but not in mice. The sweet taste induced by MCL is more intense when acidification occurs with weak acids as opposed to strong acids. MCL interacts with the human sweet receptor subunit hTAS1R2, but the mechanisms by which the acidification of MCL activates the sweet taste receptor remain largely unexplored. The work reported here speaks directly to this activation by utilizing a sweet receptor TAS1R2 + TAS1R3 assay. In accordance with previous data, MCL-applied cells displayed a pH dependence with citric acid (weak acid) being right shifted to that with hydrochloric acid (strong acid). When histidine residues in both the intracellular and extracellular region of hTAS1R2 were exchanged for alanine, taste-modifying effect of MCL was reduced or abolished. Stronger intracellular acidification of HEK293 cells was induced by citric acid than by HCl and taste-modifying effect of MCL was proportional to intracellular pH regardless of types of acids. These results suggest that intracellular acidity is required for full activation of the sweet taste receptor by MCL.

A pilot study was conducted to evaluate the suitability of stable isotope analysis for inferring the feeding histories of cattle fed known feeds. Stable isotope ratios of carbon and nitrogen (δ 13 C and δ 15 N) were measured in meat and hair from cattle and in their feeds at five farms in different regions of Japan, and the correlations of the isotope ratios between meat and hair were analysed. The results showed that δ 13 C values in feed depend on the photosynthesis type: C 3 or C 4 . The values of δ 15 N in feeds varied widely, indicating divergent feeds made from plant materials that have different nitrogen origins, such as soil, chemical fertilizer, manure and air. In both cattle meat and hair, the farms differed significantly in the values of δ 13 C and δ 15 N. Both δ 13 C and δ 15 N were significantly higher in hair than in meat, and high correlations between meat and hair in both δ 13 C and δ 15 N were found. The results suggested that stable carbon and nitrogen isotope analysis for cattle meat and hair could be used to trace the feeding histories of cattle in Japan, and that hair samples would be used as an alternative to meat.

Four wethers were used in a 4 × 4 Latin square design experiment to evaluate the applicability of two types of total mixed ration (TMR) silage with food by-products. Four food by-products (i.e., potato waste, soy sauce cake, soybean curd residue and noodle waste) were obtained and mixed with commercial concentrate (CC) as TMR silage. The two types of TMR silage, T1 and T2, each contained CC, in addition to all by-products for T1 (TRE1), and soy sauce cake and noodle waste for T2 (TRE2) on a dry matter (DM) basis. The silage was well-fermented with low pH values and high lactic acid concentration. As the experimental treatments, T1, T2 and CC (CTL) were fed with a basal diet. The result showed that the digestibility of DM and organic matter (OM) were higher for T1 than for CC (P < 0.05), while crude protein digestibility was not significantly different among T1, T2 and CC. The retained nitrogen was not affected by inclusion of food by-products. Ruminal pH in TRE1 and TRE2 immediately decreased compared to that in CTL. The study suggested that the two types of TMR silage, including food by-products, might be used as a substitute for commercial concentrate.

Data of 20 balance measurements from Holstein dairy cows and urine samples from 24 Japanese Black beef cows were collected to evaluate the relationships between urine pH and electrolyte status in cows fed forages. The ratio of forages in the diet was 70-100% in dairy cows and beef cows were fed Italian ryegrass silage and wheat bran. Mean urine pH in dairy cows was 8.10, ranging from 7.27 to 8.71, and that in beef cows was 7.73, ranging from 7.42 to 8.12. There were positive correlations between urine pH and urinary K contents (P = 0.0012) or K intake (P = 0.019) in dairy cows, although plasma Na, Cl and K had no effect on urine pH. There was a weak negative correlation (P = 0.039) between urine pH and urinary Na content in dairy cows. However, there were no significant correlations between urine pH and urinary Na, Cl and K contents in beef cows. These results indicate that the concentrated urinary K due to the increased K intake may directly enhance urine pH in dairy cows fed mainly forages.

Culturing bamboo with the white-rot fungus Ceriporiopsis subvermispora improved its nutritive value for ruminants. The bamboo substrate was prepared by grinding madake bamboo ( Phyllostachys bambusoides ) culm into a fibrous powder, mixing it with rice bran at an air-dry weight ratio of 19:1, then sterilizing the mixture at 118 °C for 40 min. After inoculating wheat grain spawn of C. subvermispora , the bamboo substrate was cultured at 28 °C for 10 and 15 weeks. For in vivo digestion, mixed bamboo substrate (MBS) cultured for 10 or 15 weeks was used. Three sheep were each assigned to a diet group in a 3 × 3 Latin square experiment and fed either a basal diet composed of alfalfa hay cubes, wheat bran and soybean meal (699:201:100, on dry basis), 303 g/kg of a basal diet replaced with bamboo or MBS. Organic matter (OM), neutral detergent fiber excluding residual ash (NDFom), acid detergent fiber excluded residual ash (ADFom), and lignin(sa) content of the bamboo substrate before inoculation decreased ( P C. subvermispora . The OM, NDFom and lignin(sa) content of the bamboo substrate cultured with C. subvermispora for 10 weeks were higher ( P in vitro OM digestibility (IVOMD), in vitro NDFom digestibility (IVNDFomD), and in vitro gas production during 48 h of incubation (IVGP) increased ( P C. subvermispora . NDFom and lignin(sa) content of bamboo used in in vivo digestion were 905 g/kg DM and 198 g/kg DM, respectively. NDFom and lignin(sa) content of MBS were 703 g/kg DM and 106 g/kg DM, respectively. The IVGP and IVOMD of bamboo were 19 ml/g OM and 0.133, respectively, while those of MBS increased to 150 ml/g OM and 0.671. The coefficients of apparent OM, NDFom and ADFom digestibility of bamboo were 0.129, 0.127 and 0.149, respectively, while those of MBS increased ( P C. subvermispora is capable of improving the nutritive value of bamboo that can then be used as a ruminant feed.

Overexpression of an anti-apoptotic protein cIAP1 caused by its genetic amplification was reported in certain cancers, such as hepatocellular carcinoma, esophageal squamous cell carcinoma, cervical cancer, and lung cancer, which confers resistance to chemotherapy and radiotherapy. Here we report cIAP1 to be selectively down-regulated by a class of small molecules ((-)-N-[(2S,3R)-3-amino-2-hydroxy-4-phenyl-butyryl]-l-leucine methyl ester (ME-BS)), resulting in a sensitization of cancer cells to apoptosis. ME-BS directly interacts with the BIR3 domain of cIAP1, promotes auto-ubiquitylation dependent on its RING domain, and facilitates proteasomal degradation of cIAP1. Other IAPs such as XIAP and cIAP2 were not affected by ME-BS. These results suggest targeted destabilization of cIAP1 by small molecules as a novel method to treat cancers expressing cIAP1, which interferes with treatment. Manipulation of the intrinsic ubiquitin-ligase activity could be a novel strategy to develop small molecules for therapeutic purposes.

It is necessary to consider variations of circuit element values for power electronic converter design to satisfy a given specification for a frequency characteristic or a dynamic transient response because the variations of element values generate those of the designed characteristic. Therefore element values and their variation ranges should be designed to give a satisfactory characteristic within an allowable specification range or a tolerance. This analysis is so-called tolerance or worst-case analysis. The analysis is a sort of nonlinear minimum and maximum (min/max) problem with respect to circuit or system parameters. However it is not possible to solve a transient type problem generally. Hence, the problem is converted to a simpler and easier one with various techniques. This paper proposes a new Genetic Algorithm (GA) method, or a sort of a modified relay-search-GA, which is suitable for practical and efficient tolerance analysis by considering diversity of solutions. Output voltage analysis examples of three types of converters for element parameter variations are investigated for effectiveness of the proposed method.

We investigated the plasma concentration and urinary excretion of vitamin C in cows supplemented with vitamin C. Five cows (mean BW = 597 kg) were allocated to a 5 x 5 Latin square design and supplemented with a vitamin C preparation coated with hydrogenated soybean oil at 0, 10, 20, 40, or 60 mg of vitamin C per kg of BW per day for 9 d. Plasma and urine samples were collected for measuring vitamin C concentration. Urinary excretion of vitamin C was expressed as the ratio of vitamin C to creatinine. Plasma vitamin C concentration and urinary vitamin C excretion increased quadratically as dietary vitamin C increased (P < 0.001); that is, the lowest dose affected neither plasma vitamin C concentration nor urinary vitamin C excretion but the plasma vitamin C concentration and urinary vitamin C excretion increased (P < 0.05) with increasing supplementation of vitamin C at greater doses. This suggests that plasma vitamin C concentration affects urinary excretion of vitamin C in cattle and that plasma vitamin C concentration exceeded the renal threshold for vitamin C in the cows receiving vitamin C at 20 mg/kg of BW per day. Furthermore, increased urinary excretion of vitamin C appears to limit plasma vitamin C concentration in response to vitamin C intake. The daily excretion of vitamin C was estimated by the reported value of daily creatinine excretion, indicating that the daily amount of vitamin C excreted into urine was more than half of supplied vitamin C. Therefore, a large part of supplied vitamin C probably escapes ruminal degradation and is absorbed but excreted into urine.

This study was conducted to determine the effects of dietary soybean curd residue (SCR) and soy sauce cake (SSC) on the growth performance, carcass traits and physiochemical and intramuscular fatty acid (FA) characteristics in Japanese Black steers. Ten steers (29.7 ± 0.3 months old, 856.6 ± 24.4 kg body weight) were assigned to either treatment C, fed a conventional concentrate or T, fed the test diet including dried SCR and SSC for 3 months. In growth performance, dry matter (DM) intake and average daily gain, and carcass traits did not differ significantly between the treatments. Color of beef was affected by the dietary treatments and meat samples from T showed higher a(*) value and chroma than those in C. On FA composition, there was no significant difference between the treatments in neutral lipids, whereas in polar lipids, meat samples from T had higher C16:1 (P < 0.05) and tended to have higher C16:0 (P = 0.05) and C18:1 (P = 0.08), but lower C17:0 (P = 0.098), C18:2 (P = 0.06) and C20:4 (P = 0.07) than those from C. The study suggested that SCR and SSC could be used as a substitute for conventional concentrate and would influence meat color and intramuscular FA composition of polar lipids.

7-Ethyl-10-hydroxy-camptothecin (SN-38), a biological active metabolite of irinotecan hydrochloride (CPT-11), has potent antitumor activity but has not been used clinically because it is a water-insoluble drug. For delivery by i.v. injection, we have successfully developed NK012, a SN-38-releasing nanodevice. The purpose of this study is to investigate the pharmacologic character of NK012 as an anticancer agent, especially in a vascular endothelial growth factor (VEGF)–secreting tumor model. The particle size of NK012 was ∼20 nm with a narrow size distribution. NK012 exhibited a much higher cytotoxic effect against lung and colon cancer cell lines as compared with CPT-11. NK012 showed significantly potent antitumor activity against a human colorectal cancer HT-29 xenograft as compared with CPT-11. Enhanced and prolonged distribution of free SN-38 in the tumor was observed after the injection of NK012. NK012 also had significant antitumor activity against bulky SBC-3/Neo (1,533.1 ± 1,204.7 mm3) and SBC-3/VEGF tumors (1,620.7 ± 834.0 mm3) compared with CPT-11. Furthermore, NK012 eradicated bulky SBC-3/VEGF tumors in all mice but did not eradicate SBC-3/Neo tumors. In the drug distribution analysis, an increased accumulation of SN-38 in SBC-3/VEGF tumors was observed as compared with that in SBC-3/Neo tumors. NK012 markedly enhanced the antitumor activity of SN-38, especially in highly VEGF-secreting tumors, and could be a promising SN-38-based formulation. (Cancer Res 2006; 66(20): 10048-56)

The potential of five white-rot fungi to convert Japanese red cedar ( Cryptomeria japonica ) into feed for ruminants was determined. Pleurotus ostreatus (ATCC 66376), Pholiota nameko (IFO 30373), Dichomitus squalens (CBS 432.34), Lentinula edodes (IFO 6654) and Ceriporiopsis subvermispora (ATCC 90467) were inoculated into chips of cedar sapwood. L. edodes was cultured at 25 °C, and the other fungi at 28 °C, for 4, 8, 12, or 20 weeks. The in vitro organic matter (OM) digestibility (IVOMD) in cedar wood cultured without fungus were between 0.047 and 0.068, while it was elevated to 0.446 by culturing with C. subvermispora and to 0.281 by culturing with L. edodes for 20 weeks. In contrast, the IVOMD were 0.200, or lower, in cedar wood cultured with P. ostreatus , P. nameko , or D. squalens . The in vitro gas production (IVGP) in cedar wood cultured with P. ostreatus , P. nameko , or D. squalens was 37 ml/g OM, or lower, while that in cedar not inoculated with fungus was between 4 and 17 ml/g OM. In contrast, the IVGP in cedar wood cultured with C. subvermispora for 20 weeks increased to 107 ml/g OM, and that in cedar wood cultured with L. edodes increased to 58 ml/g OM. Lignin degradability in cedar wood cultured with C. subvermispora and L. edodes for 20 weeks were 0.578 and 0.288, respectively. These changes in IVOMD and IVGP demonstrate that a selective white-rot fungus, C. subvermispora has the ability to convert cedar wood into feed for ruminants, although further increase is required before the cultured cedar wood would have widespread feed potential.

石英繊維フィルターに捕集された大気粉じんのPIXE法による元素分析の確立を目的に, 小型チャンバー等を用いてPd-carbon粉末を混入させたNIST標準物質 (Urban Particulate Matter; SRM 1648) を石英繊維フィルター (Pallflex Fiber Filter, Model 2500 QAST, 47mmφ) 上に捕集し, 硝酸による簡便な化学的前処理を行い, フィルター上からのNIST標準物質の脱離状況と分析精度を検討した。フィルター試料からのNIST標準物質は, 簡便な小型容器を用いた硝酸―マイクロウェーブ法によりほぼ完全に脱離していることが確認できた。PIXE分析による元素定量値は, NIST標準物質の認証値及び参考値に対して70～110%で, 概ね一致する結果が得られた。

Vitamin A is one of the micronutrients which have been implicated in cattle reproduction. In cattle, ingested vitamin A, mainly as beta-carotene (BC) from forages and retinol ester from formula feed, is metabolized and transported to the oocytes and cumulus-granulosa cells in ovarian follicles through binding to various interacting molecules. The active form of vitamin A, retinoic acid (RA), functions as a regulator of gene expression in these targets. Early research showed the positive effects of vitamin A supplementation on bovine fertility in artificial insemination, and several studies on effects of vitamin A metabolites used in other artificial reproductive techniques (ART), including superovulation, ovum pick up, and in vitro maturation culture have provided evidence for the specific roles of vitamin A in oocyte cytoplasmic maturation (acquisition of developmental competence of oocytes during their meiotic maturation period for the embryonic development after fertilization). BC may enhance cytoplasmic maturation by its antioxidant properties which cannot be replaced by RA. Furthermore, RA may promote cytoplasmic maturation of bovine oocytes via its modulatory effects on the gene expression of gonadotrophin receptors, midkine, cyclooxygenase-2, and nitric oxide synthase in cumulus-granulosa cells.

肉牛肥育－水稲複合生産農家における窒素の利用状況を窒素循環も含めて評価することを目的として事例研究を行った．肉牛肥育－水稲複合生産システムを肉牛肥育，堆肥，水稲生産，作物/農業副産物の4部門に分割し，各部門の窒素収支を定量化した．窒素の利用状況の評価は，窒素効率，窒素循環そして窒素ロスについて行った．農家全体の窒素効率は0.39であり，農家に投入した窒素のうち39％が生産物として産出された．窒素循環は，各部門に投入された窒素のうち産出後，他部門へ移動した窒素の割合で表し，その割合は0.30～0.97であった．窒素ロスは肉牛肥育部門でもっとも大きく，肉牛肥育生産から窒素が環境に放出される可能性が示された．以上より，複合生産システムにおける窒素の利用状況と窒素循環が量的に明らかにされ，本研究で用いた手法が農家レベルでの窒素の利用状況を窒素循環も含めて評価するのに有効と考えられた．

牛肉の経済価値を決定する上で重要な形質となっている脂肪交雑を，肥育開始前あるいは肥育開始後の初期に早期判定する技術の確立が望まれている．そこで，脂肪交雑早期判定の手掛りを得る目的のもとに，脂肪細胞への分化の促進に関わる核内転写因子，CCAAT/enhancer-binding protein (C/EBP)α, C/EBPβ, C/EBPδ, およびPeroxisome proliferator-activated receptor (PPAR) γの最長筋での月齢にともなった発現パターンを，脂肪交雑の能力に遺伝的な差をもつ黒毛和種牛とホルスタイン種牛との間で比較した．各品種3頭について，最長筋サンプルを2ヵ月齢から2ヵ月ごとに16ヵ月齢まで，バイオプシーにより採取した．各遺伝子の発現レベルはcompetitive PCRにより測定した．その結果，ホルスタイン種に比べて，黒毛和種では，最初にC/EBPδの発現が有意に上昇し（6ヵ月齢でP＜0.01），6ヵ月齢をピークに減少する，6ヵ月齢からC/EBPβの発現が有意に上昇する（8ヵ月齢でP＜0.01），さらに肥育開始後においてPPARγの発現が有意に上昇する（16ヵ月齢でP＜0.01）という特有な変化パターンが認められた．このように，若齢期に品種間に差があり，しかもその差とBMSナンバーとの間に関連が認められる遺伝子を同定することで，肥育開始前にウシ脂肪交雑を早期判定することが可能になると考えられる．C/EBPβおよびC/EBPδはその候補となるかもしれない．

Plasma vitamin C (ascorbic acid + dehydroascorbic acid) concentration is a good index of the nutritional status of vitamin C. However, the methodologies for storage and analyses have not been investigated in bovine plasma. The validity of an analytical method for bovine plasma using high performance liquid chromatography (HPLC) with a spectrophotometric detector was examined. Exogenous dehydroascorbic acid was almost completely converted to ascorbic acid during the preparation for analysis with a reducing reagent, dithioerythritol. The analytical recoveries of ascorbic acid were high. Ascorbic acid was not detected after treatment with ascorbic acid oxidase. Thus, the specificity of this method is considered to be high. Although vitamin C was stable in plasma treated by dithioerythritol at −20°C for 6 days, vitamin C in untreated plasma significantly decreased during 3-day storage at −20°C. These results indicate that the HPLC method is suitable for the determination of plasma vitamin C in cattle and that the storage conditions are important for determination of plasma vitamin C. Plasma vitamin C concentration ranged between 1.49 mg/L and 3.33 mg/L in fattening cattle. This result suggests that fattening cattle show large individual variation in plasma vitamin C concentration.

This study evaluated the efficacy of adding pioglitazone 30 mg to the therapy of patients with type 2 diabetes mellitus whose glycaemic control was poor on an alpha-glucosidase inhibitor (alpha-GI) alone or in combination with a sulphonylurea (SU). The patients (n = 20) had a HbA(1c) level between 7.0 and 12.0% and the fasting plasma glucose was 7.8 mmol/l or higher. They were treated with 30 mg pioglitazone once daily for 16 weeks. The decrease in HbA(1c) at week 16 of treatment was 0.8% (7.8% at baseline dropping to 7.1% at week 16; p < or = 0.01). An increase in leptin was observed 4 weeks after starting the post-study period (p < or = 0.05). Tumour necrosis factor-alpha (TNF-alpha) and body fat percentage did not show any significant alterations. Correlations between the decrease in HbA1c at week 16 and characteristic variables of patients were examined. A correlation with leptin (p = -0.5632, p < or = 0.05) levels was found. Five patients experienced adverse drug reactions, such as oedema, hypoglycaemia and increased creatine phosphokinase (CK), all of which were mild in severity. The addition of pioglitazone in diabetics whose glycaemic control was poor on a alpha-GI alone or with a alpha-GI and SU combination resulted in a significant decrease in HbA1c, and the treatment was well-tolerated. Our findings also suggest that leptin levels could be useful for assessing responders to pioglitazone.

A new HPLC gradient system was developed for (32)P-postlabeling analysis to identify and quantify hepatic tamoxifen-DNA adducts of rats and mice treated with tamoxifen. Four stereoisomers of alpha-(N(2)-deoxyguanosinyl)tamoxifen (dG(3')(P)-N(2)-TAM), alpha-(N(2)-deoxyguanosinyl)-N-desmethyltamoxifen (dG(3')(P)-N(2)-N-desmethyl-TAM), and alpha-(N(2)-deoxyguanosinyl)tamoxifen N-oxide (dG(3')(P)-N(2)-TAM N-oxide) were prepared by reacting either alpha-acetoxytamoxifen, alpha-acetoxy-N-desmethyltamoxifen or alpha-acetoxytamoxifen N-oxide with 2'-deoxyguanosine 3'-monophosphate, and used as standard markers for (32)P-postlabeling/HPLC analysis. Our HPLC gradient system can separate the above 12 nucleotide isomers as nine peaks; six peaks representing two each trans epimers (fr-1 and fr-2) of dG(3')(P)-N(2)-TAM, dG(3')(P)-N(2)-N-desmethyl-TAM and dG(3')(P)-N(2)-TAM N-oxide, and three peaks representing a mixture of two cis epimers (fr-3 and fr-4) of nucleotides. Tamoxifen was given to female F344 rats and DBA/2 mice by gavage at doses of 45 mg/kg/day and 120 mg/kg/day, respectively, for 7 days. Totally 15 and 17 tamoxifen-DNA adducts were detected in rats and mice, respectively; among them 13 adducts were observed in both rats and mice. trans-dG-N(2)-TAM (fr-2) and trans-dG(3')(P)-N(2)-N-desmethyl-TAM (fr-2) were two major adducts in both animals. Except for these two adducts, trans-dG-N(2)-TAM N-oxide (fr-2) was the third abundant adduct that accounted for 6.4% of the total adducts in mice, while this accounted for only 0.3% in rats. A trans-isomer (fr-1) and cis-isomers (fr-3 and -4) of dG(3')(P)-N(2)-TAM, dG(3')(P)-N(2)-N-desmethyl-TAM and dG(3')(P)-N(2)-TAM N-oxide were also detected as minor adducts in both animals except for cis-form of dG-N(2)-TAM N-oxide in rats. Although the administered dose for rats was 2.7-fold less than that for mice, the total adduct level of rats (216 adducts/10(8) nucleotides) were 3.8-fold higher than mice (56.2 adducts/10(8) nucleotides). Thus, these three types of tamoxifen adducts accounted for 95.0 and 92.5% of the total DNA adducts of the rats and mice, respectively. The formation of tamoxifen adducts primarily resulted from alpha-hydroxylation of tamoxifen.

(-)-(3S, 4R, 1'R, 6'S)-4-(4-Benzyl-5-oxo-3, 4-diazabicyclo[4.1.0]hept-2-en-2-yloxy)-3, 4-dihydro-3-hydroxy-2, 2-dimethyl-2H-1-benzopyran-6-carbonitrile and its derivatives with a modified benzyl group were synthesized with the objective of discovering novel ATP-sensitive potassium channel openers (PCOs) with a slow onset of action and a reduced tendency to induce tachycardia. Among the compounds synthesized, 4-(2-chlorobenzyl) derivative 5bB had potent hypotensive activity in spontaneously hypertensive rats (SHRs). In addition, compound 5bB showed the desired pharmacological profile with a slow onset and long duration of action and induction of only mild tachycardia. Compound 5bB was found to be quantitatively metabolized in rats to give active des-2-chlorobenzyl derivative 6B. These results suggest that the incorporation of an N-benzyl group is a useful method for the preparation of prodruge, the function of which is to delay the onset and prolong the duration of action of the active substance.

Synthesis and hypotensive activity of trans -3,4-dihydro-3-hydroxy-4-[(5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2-yl)oxy]-2 H -1-benzopyrans and their congeners are described. Compounds (−)- 9eB and (−)- 20B were highly potent ATP-sensitive potassium channel openers.

The octahydronaphthopyranone moiety is synthesized from methyl α- d -mannopyranoside through the intramolecular Diels-Alder reaction, and the tetraenedicarboxylic acid moiety is from the enzymatically prepared anti-compound. Both moieties were coupled to accomplish the total synthesis of calbistrin A and to disclose its absolute structure.

Nerve growth factor (NGF) is known to have key roles in neural protection and repair of central and peripheral neurons.1 NGF was reported to ameliorate several neuronal dysfunction and injury in animal models,2, 3 and has been applied to clinical trial.4 Because of its protein property, NGF is thought unsuitable for oral administration and insufficient for blood–brain barrier penetration. So far low-molecular-weight compounds having NGF mimetic activity have been screened and neurite-inducing compounds such as lactacystin5 and K-252a6 were isolated from microbial resources. A chemically synthesized compound of AIT-012 was reported to enhance NGF-induced neurite outgrowth and has been applied to clinical trail.7 In this report we describe isolation of a novel NGF mimetic compound and show its physico-chemical properties and biological activities of the compound named as cystacyclin.

Stevastelin B, obtained from a culture of a Penicillium sp. NK374186, is a novel depsipeptide containing three amino acids and 3,5-dihydroxy-2,4-dimethylstearic acid. The stereochemistry of the three amino acids was determined by HPLC analysis, and the relative configuration of the 3,5-dihydroxy-2,4-dimethylstearic acid was elucidated by chemical conversion and NMR analysis. The absolute stereochemistry of stevastelin B was determined by synthetic methods.

The first enantiospecific total synthesis of gualamycin has been accomplished by coupling the thioglycoside of the amino-disaccharide portion with the strained di-O-benzylidene derivative of the pyrrolidine-aglycone.

A novel acaricide, gualamycin was isolated from the culture broth of Streptomyces sp. NK11687. The structure of gualamycin was determined to be (2R,3S,4S)-2-O-[4-O-(2-amino-2-deoxy-beta-D-gulopyranosyl)-alpha-D - galactopyranosyl]-2,3,4-trihydroxy-4-[(2S,3S,4S,5S)-3,4-dihydroxy-5-hydr oxy - methylpyrrolidin-2-yl] butanoic acid by FAB-MS, 1H and 13C NMR, COSY, HMQC, HMBC, IR, X-ray crystallographic analyses and synthetic studies.

Four wethers were used in a 4 × 4 Latin square design experiment to evaluate the applicability of two types of total mixed ration (TMR) silage with food by-products. Four food by-products (i.e., potato waste, soy sauce cake, soybean curd residue and noodle waste) were obtained and mixed with commercial concentrate (CC) as TMR silage. The two types of TMR silage, T1 and T2, each contained CC, in addition to all by-products for T1 (TRE1), and soy sauce cake and noodle waste for T2 (TRE2) on a dry matter (DM) basis. The silage was well-fermented with low pH values and high lactic acid concentration. As the experimental treatments, T1, T2 and CC (CTL) were fed with a basal diet. The result showed that the digestibility of DM and organic matter (OM) were higher for T1 than for CC (P0.05), while crude protein digestibility was not significantly different among T1, T2 and CC. The retained nitrogen was not affected by inclusion of food by-products. Ruminal pH in TRE1 and TRE2 immediately decreased compared to that in CTL. The study suggested that the two types of TMR silage, including food by-products, might be used as a substitute for commercial concentrate.

症例は72歳,女性.近医より高血糖を指摘され,受診.初回入院時から尿中CPRが低値であった事と臨床経過より, Slowly progressivel型糖尿病(SP1型糖尿病)を疑い, GAD (Glutamic Acid Decarboxylase)抗体の測定をしたが陰性であった.以後経時的にGAD抗体の測定を行っていたが,発症9年目の平成12年入院時に初めてGAD抗体が陽性となった.本症例はGAD抗体が陰性から陽性化したSP1型糖尿病で,興味深い症例と思われた.

Data of 20 balance measurements from Holstein dairy cows and urine samples from 24 Japanese Black beef cows were collected to evaluate the relationships between urine pH and electrolyte status in cows fed forages. The ratio of forages in the diet was 70-100% in dairy cows and beef cows were fed Italian ryegrass silage and wheat bran. Mean urine pH in dairy cows was 8.10, ranging from 7.27 to 8.71, and that in beef cows was 7.73, ranging from 7.42 to 8.12. There were positive correlations between urine pH and urinary K contents (P = 0.0012) or K intake (P = 0.019) in dairy cows, although plasma Na, Cl and K had no effect on urine pH. There was a weak negative correlation (P = 0.039) between urine pH and urinary Na content in dairy cows. However, there were no significant correlations between urine pH and urinary Na, Cl and K contents in beef cows. These results indicate that the concentrated urinary K due to the increased K intake may directly enhance urine pH in dairy cows fed mainly forages.

1-Deoxynojirimycin (1,5-dideoxy-1,5-imino-D-glucitol) was converted, via epoxide intermediates, into a series of N-acetyl-hexosamine analogs, i. e., 2-acetamido-1,2,5-trideoxy-1,5-imino-D-glucitol, 2-acetamido-1,2,5-trideoxy-1,5-imino-D-mannitol, 2-acetamido-1,2,5-trideoxy-1,5-imino-D-galactitol, and their isomers. The cyclic 5-N,6-O-carbamoyl derivatives of 1-deoxynojirimycin were also prepared.

The octahydronaphthopyranone moiety is synthesized from methyl α- d -mannopyranoside through the intramolecular Diels-Alder reaction, and the tetraenedicarboxylic acid moiety is from the enzymatically prepared anti-compound. Both moieties were coupled to accomplish the total synthesis of calbistrin A and to disclose its absolute structure.

Synthesis and hypotensive activity of trans -3,4-dihydro-3-hydroxy-4-[(5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2-yl)oxy]-2 H -1-benzopyrans and their congeners are described. Compounds (−)- 9eB and (−)- 20B were highly potent ATP-sensitive potassium channel openers.

A series of 3,4-dihydro-3-hydroxy-4-[(5-oxo-3,4-diazabicyclo[4.1.0]hept- 2-en-2-yl)oxy]-2H-1-benzopyrans and their analogues were synthesized and evaluated on potassium channel opening and hypotensive activities. Compound (-)-13B with a (4-methyl-5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2-yl)oxy group for the 4-position of the benzopyran ring was 3 times as potent as EMD 57283 (II), the lead compound, in hypotensive activity. The results would demonstrate that 5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2-yloxy moieties are effective as the substituents at the 4-position of benzopyran-type potassium channel openers.