All Data

抗がん剤の副作用である口腔粘膜炎の改善にはエレンタール^(R)は有効であることが報告されている。5-フルオロウラシル (5-FU) の副作用には口腔粘膜炎がある。そこでエレンタール^(R)の中で口腔粘膜炎の改善に最も有用な成分の特定を試みた。マウス（対照群を除く）に5-FUを4日間腹腔内注射し、生理食塩水（対照群、5-FU群）、デキストリン（デキストリン群）、アミノ酸（17AA群）、エレンタール^(R)（エレンタール^(R)群）のいずれかを7日間投与した。

本研究の目的は、健常人において、血漿中の尿酸値（UA）と分枝鎖アミノ酸および芳香族アミノ酸（BCAAおよびAAA）の濃度の関連を明らかにすることである。 合計2,804人の健常人について、血漿UAレベルに応じて3つのグループに分類した。その3グループ間における、BCAAとAAAの濃度の関連を、分散分析（ANOVA）と共分散分析（ANCOVA）により解析した。 この研究で対象としたすべてのBCAAとAAAの濃度は、トリプトファンを除き、全てがUA濃度の各レベルに応じて、漸進的に有意に増加した（P<0.001）。また、全体として、個々のBCAAおよびAAAについて、最低のカテゴリーの差にくらべ、高いカテゴリーの差の方が、より大きかった。本研究は、血漿中のBCAAおよびAAAと、UAのレベルについて、潜在的に、密接な関係が存在していることを示唆した。今後、それらの間の因果関係および相互作用を解明する研究が必要である。

Nutrient pollution is one of our most pervasive, expensive, and challenging environmental problems, according to the United States Environmental Protection Agency (EPA). Phosphorus is one of the nutrients that are essential for the growth of living organisms. However, excessive amounts of nutrients released into the environment by human activities can harm ecosystems and impact human health. In surface waters, phosphorus can contribute to an overgrowth of algae called algal "blooms" that can sicken or kill wildlife and endanger aquatic habitats. Algal blooms consume dissolved oxygen in the water, leaving little or no oxygen for fish and other aquatic organisms. Algal blooms can harm aquatic plants by blocking the sunlight they need to grow. Some algae produce toxins and encourage the growth of bacteria that can make people sick who are swimming or drinking water or eating contaminated fish or shellfish. Phosphorus is often a major limiting nutrient freshwater system. Consequently, many of the wastewater treatment plant discharged into freshwater systems such as lakes, ponds, and rivers have phosphorus discharge limits. In an attempt to prevent harmful environmental effects of excess phosphorus, several techniques have been designed to remove phosphorus from wastewater. These techniques range from adsorption and precipitation to enhanced biological phosphorus removal and constructed wetlands. Biological phosphorus removal (BPR) was first used at a few water resource recovery facilities in the late 1960s. A common element in EBPR implementation is the presence of an anaerobic tank (no nitrate and oxygen) before the aeration tank. In the next aerobic phase, these bacteria can accumulate large amounts of polyphosphate in their cells and phosphorus removal is said to be increased. The group of microorganisms that are largely responsible for P removal are known as the phosphorus accumulating organisms (PAOs). One of the options to remove phosphorus is to utilize bacteria from nature, besides being easy to obtain and inexpensive. The application of bacteria from sediment and seawater was able to reduce phosphorus in wastewater. In this study, for screening salt-tolerant phosphorus accumulating organisms (PAOs) and investigating the P release and uptake of the organisms in saline wastewater. The samples used were sediment and seawater from Yamaguchi Bay, Yamaguchi, Japan. Sediment and seawater added 150 mL of artificial saline wastewater with media (anaerobic media). The samples were then cultured and given feed media every three hours day at 25 °C and shaken at 140 rpm. The hydraulic retention time of the cultivation was 16 h and 8 h under anaerobic and aerobic conditions, respectively. 10 sponges made of polyurethane with dimensions of 2 cm were put in Erlenmeyer flasks and was used as a bio-carrier surface for microorganisms to adhere to. Water was passed over the sponge surface to acclimatize the microorganisms growing outside the sponge as well as within its pores, ensuring sufficient growth surface. The cultivation duration was 112 days. Batch experiments were conducted over 98 days in solutions with a salinity of 3.5% and P concentrations of 1, 5, 10, and 20 mg-P/L. The P-uptake ability of microorganisms increased by increasing P concentration from 1 to 20 mg-P/L. A high P removal percentage with an average of 85% was obtained at 10 mg-P/L after day 56. The uptake and release of P were observed in saline wastewater, signifying that salt-tolerant PAOs could grow in the saline solution. Bacterial screening by isolation and sequence analysis using 16S rRNA demonstrated that two cultivated strains, TR1 and MA3, had high similarity with Bacillus sp. and Thioclava sp. EIOx9, respectively. The colony morphology analysis showed that the colonies of TR1 were rod-shaped, milky-colored, round, shiny-viscous, smooth with a defined margin, while colonies of MA3 were cream-colored with smooth surfaces and raised aspect. The TR1 was gram-stain-positive with approximately 6-10 μm long and 1.2 μm wide cells, and MA3 was gram-stain-negative with about 0.9 μm long and 0.5 μm wide cells. The results demonstrated the involvement of Bacillus sp., and Thioclava sp. in the release and uptake of P, owing to their ability to grow in saline wastewater. Furthermore, Bacillus sp. (TR1) and Thioclava sp. (MA3) were assessed for their abiotic adaptability and phosphorus removal efficiency in saline wastewater. The effects of abiotic factors such as carbon source, pH, temperature, and salinity on bacterial growth were examined through a series of batch experiments. Both bacteria used carbon sources such as glucose, sucrose, and CH3COONa for their growth. The pH study indicated that Bacillus sp. (TR1) preferred the pH range of 6 8 and Thioclava sp. (MA3) preferred the pH range of 6-9. Bacillus sp. favorably multiplied in the temperature range of 25- 40 °C, while 25 35 °C was preferred by Thioclava sp. Salinity range of 0% 10% was favorable for TR1, with optimum growth observed at 3.5% 5%, and Thioclava sp. (MA3) preferred the salinity range of 1% 10% with optimal growth at 4%, but was absent in non-saline water. Bacillus sp. and bacterial combination (TR1 and MA3) showed similar values for phosphorus removal efficiency (100%) at 1.0 mg-P/L total P compared to Thioclava sp. (38.2%). The initial phosphorus concentration of 2.5 mg-P / L showed a slightly higher 72.35% P removal efficiency compared to the individual strains. However, phosphorus removal did not increase, but showed a downward trend with increasing at initial phosphorus. The combination possibly built a synergistic activity between the individual strains to remove phosphorus. The results demonstrated that when used individually, Bacillus sp. showed a reasonably high phosphorus removal ability than Thioclava sp., and exhibited good synergy when used in combination to remove phosphorus from saline wastewater.

Fiber-reinforced polymer (FRP) rods fabricated from unidirectional fibers and a polymer matrix strengthen effectively reinforced concrete (RC) members. The pultrusion is a production method of FRP rod. The FRP rods show various advantages, such as light and no-corrosion. Most FRP rods have higher tensile strength than standard steel bars. Therefore, the FRP rods can be used as an alternative reinforcement of steel bars in RC structures. In addition, FRP rods can be applied in near-surface mounted (NSM) systems for strengthening existing concrete structures. The tensile properties of FRP rods in adhesively bonded anchorages are expected to be studied in detail. Numerous experimental studies were conducted on FRP rods made of glass, carbon, aramid, or basalt fibers. The previous studies have reported that the tensile properties of FRP rods are affected by the shear-lag effect. However, these studies referred to the tensile failure, the shear-lag effect of FRP rods as a phenomenon without a mechanical explanation. Moreover, the effects of mechanical properties of fibers, matrix, fiber-matrix interface on FRP rod properties have not been investigated in detail. To quantify factors affecting the tensile properties of FRP rods, this study performed a numerical investigation on aramid FRP rods to assess the shear-lag effect, tensile load-capacity, and tensile strength. In addition, the effects of fiber, matrix, and fiber-matrix interface on the behavior of FRP material in three dimensions were demonstrated by micro-models. Firstly, two representative volume element (RVE) models of fibers and matrix were proposed to predict engineering constants and strengths of the FRP material in three dimensions. Based on the predicted strength, the criteria were designed. Then, the main simulation, including the FRP rod, the filling material, and the steel tube, was carried out to analyze FRP rods under the variation of interfacial conditions between materials, including full-bonding strength and partiallybonding strength models. In the partially-bonding strength model, the interfaces between materials were simulated as cohesive zone models with the variation of bond strengths and fracture energy release rate. A technique called submodeling was applied to enhance the simulation results. The submodel was cut from the main simulation model and only applied to simulate FRP rods with finer meshes. The study proposed a procedure for calculating the stress distribution in any cross-section of an FRP rod. The simulation results agreed well with the previous experimental study. The findings clearly indicated the position of the failure section in which the tensile stress distribution is unequal. The load-capacity, failure modes, shear-lag effect were predicted based on the maximum stress criterion. The results revealed that the FRP material strengths enforce the failure in two modes associated with the transverse and longitudinal directions of FRP rods. In addition, diameter is a significant factor that increases the shear-lag effect and reduces the tensile strength of the FRP rods. The numerical simulation provided a new method to predict the load-capacity of FRP rods. The study consists of 6 chapters. Outline of the chapter was presented as follows: Chapter 1 introduces about kinds of FRP rods and their application in civil engineering. The chapter shows the research objects, the gaps in composite studies, and the scopes of the present research. Chapter 2 summrizes the review of previous studies related to the theoretical studies of the composite materials. The chapter reveales the gap of theory. In addition, the study compares the advantages and disadvantages of previous studies and proposes methods and models for the present study. Chapter 3 presents the simulations of the representative volume element (RVE) models to determine the mechanical properties and strengths of composite materials. The study investigates the effects of the fiber properties and fiber-matrix interface on composite mechanical properties in detail. The RVE-1 model was employed to predict engineering constants of the FRP material. The RVE-2 was applied to predict the tensile and shear strengths in three dimensions. Chapter 4 shows the numerical simulations of the FRP rod tensile tests with various cases of the materials in Chapter 3. The models are built in two cases of the interface between the FRP rod and filling material: full-bonding and partially-bonding strengths. In the case of the full-bonding strength, three models are built with three hypotheses of FRP rod material. Three models, A, B, and C, were proposed to demonstrate the effect of fiber properties on FRP properties. Model A was built based on the hypothesis that the FRP rod is made of transversely isotropic fibers. Model B was made to simulate with an FRP rod of isotropic fibers. Model C assumes the FRP rod as an isotropic material. In the case of the partially-bonding strength, the study models various interface cases between the FRP rod and the filling materials to investigate the bonding effects. The proposed models were applied to simulate FRP rods from D3 to D8 to analyze the diameter effect. In Chapter 5, the difference between the proposed models was discussed to show the advantages and disadvantages of each model. Firstly, the study compared models (A, B, and C) to highlight the effect of fiber properties on FRP rods. Secondly, the study compared the partially-bonding strength and full-bonding strength models to investigate the bonding effects on the tensile properties of FRP rods. Moreover, the chapter illustrates the existence of the shear-lag effect and demonstrates the diameter effect on tensile strength in FRP rods. Chapter 6 summarizes the novel findings and research significance of the study. In addition, recommendations for future works were also presented.

新規ヒトin vitroおよびex vivo BBBモデル，in vivo モデルを用いて，NMOSDの病態生理とサトラリズマブの作用機序を，BBB破綻の点から検討した．血管内皮細胞に対するペリサイトおよびアストロサイトの足突起の接触を再現した3層共培養系を構築し，これを用いて静的in vitroモデルおよび流速負荷型ex vivoモデルを作製した．これらのBBBモデルを使用し，バリア機能の持続測定，白血球のmigration，NMO-IgGとサトラリズマブのBBB透過性を評価した．In vivo研究では，脊髄中でIL-6が著増するEAEマウスのin vivoでのBBB破綻に対して，マウスIL-6受容体抗体MR16-1が与える効果を評価した．In vitroおよびex vivoでの実験では，NMO-IgGがサトラリズマブおよびNMO-IgGの脳内透過性を亢進させること，サトラリズマブがNMO-IgGが誘導するT細胞のmigrationとBBB破綻を抑制することが示された．In vivo研究では，IL-6シグナル伝達の阻害によって，T細胞の脊髄への浸潤が抑制され，脊髄炎の発症が抑えられた．これらの結果から以下のことが示された．（1）我々が作製した，3層共培養によるin vitroおよびex vivo BBBモデルは，バリア機能，白血球のmigration，脳内移行性を評価するために理想的なBBBモデルである．（2）NMO-IgGは，バリア機能の減弱によってNMO-IgG自身の透過性を亢進し，アストロサイトからのIL-6分泌を誘導し，さらなるバリア機能の障害と細胞浸潤の制御破綻を引き起こす．（3）サトラリズマブは，NMO-IgGの共存下でBBB通過が容易となり，BBB機能障害と炎症細胞浸潤を抑制する結果，NMOSDの発症を予防する．

ラット坐骨神経結紮モデル（SNL）は最も一般的に神経障害性疼痛の実験に用いられるモデルラットであり、運動麻痺を生じないことでも知られている。神経障害性疼痛モデルの疼痛評価にはこれまでフォンフレイテスト（機械的アロディニア評価）と熱刺激回避テストが用いられてきた。しかしこれらのテストは臨床で用いられる神経学的検査とは全く異なる手法での評価である。神経障害性疼痛を有する患者では、両下肢の協調運動が乱れ，歩行時の下肢の動きに左右差を生じていることが多い。本研究において、私達はヒトと同様な疼痛行動や疼痛に伴う歩行障害などが実際には生じているのではないかと考え、三次元歩行解析を行いて本モデルの関節の動きや歩行時の動態解析を行った。今回の解析にはキネマトレーサーシステムを用いた。 機械的アロディニアに関するSNLの効果として術後１週間から８週間にわたり、回避行動閾値の47±6.1％の低下を認めた。ＳNLラットにおける股関節・膝関節・足関節のマーカーの矢状面の軌跡は歩行中に大きな変動を認めた。歩行中の不安定性を示す患側左股関節・膝関節の上下端の高低差は、SNLラットでほうが有意に大きかった。歩行パターンを示す、両足同時接地時間はSNLラットのほうが有意に長い結果であった。左右下肢の協調運動を評価するため、両下肢の歩行周期時間も計測した。歩行周期の左右差を示す左右比は、コントロール群のラットでは1.0±0.08と左右差がほぼないのに比較し、SNLラットでは0.62±0.15と有意に左右下肢の歩行周期が異なることが示唆された。 フォンフレイテストや熱刺激回避テストは臨床現場で使用されることのない疼痛機能評価であるが、こうした新しい三次元歩行動態解析技術を用いることができれば、神経障害性疼痛患者における疼痛行動も、定量的かつ数値化して示すことが可能になる可能性について示すことができた。従来の神経障害性疼痛モデルにおける、疼痛機能評価に関する臨床と実験モデルの大きなかけ離れについての問題点を解決し、将来的にはヒトでの機能評価にも応用できる新しい三次元歩行動態解析技術について報告し、実際のラット坐骨神経結紮モデルでのデータを示した。

オメガ3長鎖多価不飽和脂肪酸(ω-3)は海産魚や魚油に含まれる必須脂肪酸で、抗炎症効果を有することから非感染性ぶどう膜炎の有効な治療になる可能性がある。多くのぶどう膜炎でみられる獲得免疫による炎症反応は、樹状細胞（DC）、マクロファージ、およびBリンパ球を含む抗原提示細胞(APC)による抗原提示から開始され、炎症のトリガーとして重要である。これまでに我々はω-3長鎖多価不飽和脂肪酸（LCPUFA）が、実験的自己免疫性ぶどう膜炎モデル（EAU）の眼炎症を抑制することを示した。今回、ω-3によるEAUの抗炎症効果に対する APCの関与を検討し、その作用機構について解析した。 C57BL/6マウスに等カロリーに調整したω-3もしくはω-6を含有した餌で給餌し、安楽死後に回収した脾臓細胞をマイトマイシンC処理してAPCを調整した。これらをEAU誘導したマウスから単離したCD4陽性T細胞と共培養し、種々の炎症性サイトカインの発現量および3H-チミジン取り込み量を指標とした増殖能を評価した。次にω-3群のAPCをDC、マクロファージ、B細胞を含む残りの細胞群（B細胞他）に分離し、ω-3の炎症作用を担当する細胞を探索した。続いて、ω-3で賦活化したDCによる抗炎症効果を検討するため、ω-3群のDCを単離し、EAUを誘導したマウスにAdoptive transfer(養子細胞移植)し、臨床および組織学的スコアを評価した。最後にω-3がDCに直接作用して抗炎症効果を発揮するか否かを検討した。 C57BL/6由来DCとBALB/c由来CD4陽性T細胞を混合培養して混合リンパ球反応MLR(mixed lymphocyte reaction)を誘導した培養系に、代表的なω-3脂肪酸であるDHAおよびEPAを投与し、T細胞増殖能を評価した。 ω-3群のAPCは、ω-6群に比較してIFN-γ、IL-17の発現量およびT細胞増殖能を有意に低下した。その抗炎症効果はAPCから単離したマクロファージやB細胞他ではみられず、DCのみで保存された。さらに、ω-3群のDCをAdoptive transferしたEAUマウスでは、炎症スコアが有意に低下した。DHA・EPAで賦活化したDCはMLRによるT細胞増殖能を有意に抑制した。 以上より、ω-3の経口摂取によるEAUの眼炎症抑制効果は、APC、特にDCを介在して発揮されることが示された。

近年、イヌ・ネコ・フェレットといった様々な動物が愛玩動物として飼育されており、ヒトと同様に多様な感染症に罹ることが知られている。愛玩動物における感染症の治療法や診断法を確立することはOne Healthの観点でも重要で、ヒトの健康の維持に直結するような公衆衛生上重要な課題である。ネコヘルペスウイルス1（FHV-1）は猫ウイルス性鼻気管炎の原因となるヘルペスウイルスとして知られ、上部呼吸器症状や流産などを引き起こす。インフルエンザAウイルス（IAV）は人において呼吸器症状を引き起こす季節性のウイルスとして知られ、イヌ・ネコ・ブタといった様々な動物に感染することが知られている。季節性のIAV以外にも、動物の体内で生まれる遺伝子再集合体のパンデミックも問題となる。本研究では、愛玩動物に感染が認められる上記の2種類のウイルスを解析し、FHV-1の新規治療薬の提案とIAVの診断法の確立を目的とし、全2章で構成された。

Many infrastructures constructed in the period of high economic growth are currently deteriorated and need renewal / repair. Considering the future situation, new-build infrastructures should be more durable, so the use of high-strength materials capable of reducing maintenance and management costs is preferable. A suitable construction material for the future situation is an ultra-high-strength fiber-reinforced concrete (UFC). General UFCs are cured under high temperature (at 90℃ for 48 hours). Most UFC members are often made in precast-concrete factories with dedicated curing facilities. A UFC manufacturable at general ready-mixed concrete plants has been required for various constructions using cast-in-placed concrete. The study focused on the mixture design and the manufacturing method of UFC without heat-curing. The targeted strength of the UFC was 200 N/mm^2 at the concrete age of 28 days. To achieve the required performance for UFC, the experimental study was designed and conducted. The thesis consists of seven chapters, and the content of each chapter is as follows: Chapter 1 "Introduction" shows the social concern in Japan, such as the present conditions of infrastructures. In addition, the chapter summarizes the transition of high strength concrete and fiber-reinforced concrete. The research background and the purpose of this study are described in this chapter. Chapter 2 "Previous studies" shows the review of previous studies dealing with investigations on UFC. In addition, the chapter clarifies the problem of UFC manufacturing by referring to the previous studies. Chapter 3 "Mixture design", the materials and mixture proportions required for the UHPC manufacturable under ambient temperature conditions were investigated. Five types of cement and four types of powder materials were tested, as well as the fine aggregate needed to achieve proper fluidity, fiber dispersibility and strength. To achieve the appropriate flowability and adequate strength, the cement having low C_3A and high C_3S was suitable for the UHPC manufacturable at ambient temperatures. Furthermore, the mortar with W/B of 21% achieved 200 N/mm^2 at 28 days, so it can be designed as the maximum W/B for the UFC. The test result confirmed that allowable fine aggregate volume was lower than 600 kg/m^3 to obtain proper dispersion of steel fibers. Chapter 4 "Material properties and durability of hardened UFC", the hardening material properties and durability of the UFC designed in Chapter 2 were examined. The result confirmed that the UFC achieved 196 N/mm^2 at the age of 28 days. The UFC exhibited an excellent cracking strength and tensile strength which were almost equivalent strength of the conventional UFC. In addition, the UFC indicated excellent resistances to various degradation effects, such as neutralization, freezing and thawing, permeability of chloride ions, and sulfate attack. On the other hand, the UFC had low resistance to sulfuric acid and large autogenous shrinkage strain. The properties should be considered in the application of prestressed concrete owing to the loss of prestress. Chapter 5 "Manufacturing method in RMC plant" reports the manufacturing methods at the ready-mixed concrete (RMC) plant. The result confirmed that UFC can be manufactured at a general RMC plant, the equipment although mixing time varies owing to the mixer capacity. In addition, the mixing methods of steel fibers were compared. Owing to the high viscosity of the UFC, undischarged UFC from the truck was approximately 190 L, which was extremely higher than ordinary concrete (80 L). The compressive strength of UFC using several types of fine aggregate were examined. The result suggested that the evaluation of the properties of fine aggregates in the UFC is necessary for the practical use. Chapter 6 "Practical applications of UFC" verifies the applicability of UFC of at sites. The result confirmed that the mixing-load increased in proportion to the mixing volume, the maximum mixing volume was identified as 80% of the capacity of mixer. The results showed that the UFC made in a RMC plant indicated stable fresh and strength properties for a few months. Furthermore, the production of UFC with onboard mixers was tested. The result confirmed that the method reduced the material-loss during transportation. The surface-finish of UFC was also evaluated by comparing the results obtained from a soil hardness tester. Moreover, the heat curing conditions of UFC were investigated. The result confirmed that the highest temperature and the curing time for the heat curing were lower and shorter than the standard heat curing (at 90℃ for 48 hours), respectively. Chapter 7 "Conclusions" presents the remarkable conclusions in this study and further research for the practical application of the UFC.