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Nishijima, Yoshinori ; 西嶋, 義憲
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金沢大学人間社会研究域経済学経営学系<br />Persons or objects on signs seem to have a culturally preferred direction of facing (Kumakura, 1
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990). Is such a difference in direction also true of pictures on traffic signs between Japan and Germany? People in Japan and Germany drive on the left and the right side of the road, respectively. In this respect, a question arises: Does the difference between left-hand and right-hand traffic in these two countries influence the way the pictures on traffic signs face? The aim of this study is threefold: 1) to collect functionally equivalent traffic signs in Japan and Germany; 2) to compare the pictures on the signs between these countries with respect to their facing directions; and 3) to try to clarify whether and to what extent differences in facing directions are found on the traffic signs. The results are expected to contribute to the study of the relationship between writing directions and facing directions of pictures.
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Nishijima, Yoshinori ; 西嶋, 義憲
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金沢大学人間社会研究域経済学経営学系<br />This study focuses on functionally equivalent, but semantically different sign expressions in Ja
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panese and German, such as o-nori-no-sai-wa tesuri-ni o-tsukamarikudasai [Literally, “when steping on, please grip handrail”], kiiroi-sen-no uchigawani o-tachi-kudasai [please stand inside yellow line], oriru sai-wa o-oashimoto-ni gochūi-kudasai [“when getting off, please pay attention to under foot”], and o-ko-sama tsure-no kata-wa o-ko-sama-no te-o totte o-nori-kudasai [“person with child is asked to ride on taking child’s hand”] in Japanese versus its German counterpart Benutzung auf eigene Gefahr [“using at your own risk”], which are posted near escalators. This example tells us that the Japanese sign consists of four concrete sentences whereas the German one presents a simple and abstract sentence. Such correspondents cannot be adequately explained from only construal and politeness perspectives. In this study, such corresponding expressions in Japanese and German will be contrasted to find out what information is relevant to each society. The results will reveal what communicative behaviors are expected in corresponding situations between Japan and Germany, which can contribute to efficient intercultural communication.
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Nishijima, Yoshinori ; 西嶋, 義憲
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金沢大学人間社会研究域経済学経営学系<br />By comparing some functionally equivalent routine formulas in Japaneseand German in correspondin
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g situations, it is hypothesized that different strategies arereflected in formulation patterns of routine formulas in both languages. For example,different expressions are used by parents in Japanese and German if their childbumps into a post. The two expressions are often used in corresponding situations inboth Japan and Germany and can therefore be regarded as functionally equivalent,although the used strategies differ, i.e., the Japanese expression is based on sharing thedangerous situation between the parent and the child, whereas the German one focuseson providing an appropriate direction to the child. Comparing such functionallyequivalent routine formulas suggests that they reflect different strategies, includingpoliteness, in corresponding situations. This study tested this hypothesis by comparingfunctionally equivalent routine formulas uttered in corresponding apologetic situationsin the socialization process of controlling children’s social behavior in Japan andGermany. The results confirm the hypothesis and suggest that the difference in strategy influences the communicative behaviors of Japanese and German speakers. Concerning politeness, the results reveal the aspects considered polite in corresponding routineformulas of the two languages. Furthermore, the communicative normality of each language is also reflected in its respective routine formulas and focus of attention in interactions. This information may be applied toward more efficient foreign language teaching.
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Nishijima, Yoshinori ; 西嶋, 義憲
概要:
金沢大学人間社会研究域経済学経営学系<br />The aim of this paper is twofold: (1) to compare functionally equivalent English, German, and Ja
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panese sign expressions in public spaces with respect to politeness and (2) to reveal whether and how politeness is formulated in sign expressions in each language in relation to explicitness. A total of 208 Japanese and 198 German sign expressions were collected through fieldwork. Among them, 35 functionally equivalent correspondence pairs between the two languages were confirmed, and they were compared, along with their English equivalents, with respect to politeness. The results showed that English signs tend to use explicit expressions, whereas Japanese signs frequently contain honorific items, and German signs use infinitive phrases to avoid mentioning personal relationships. Based on these findings, it is pointed out that each language has its preferred styles of politeness, even for sign expressions, which are expected to give relevant information or instructions to passengers in a clear, direct manner.
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Nishijima, Yoshinori ; 西嶋, 義憲
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金沢大学人間社会研究域経済学経営学系<br />Interest in the linguistic study of perspectives from which linguistic expressions are formulate
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d has been revived in the past 20 years, due to the recent development of cognitive linguistics. Among the many contributions to the study of such perspectives, Ikegami (2000) clearly showed that Japanese differs from English, through a comparison of a Japanese literary text with its English translation. However, there has been little discussion on the methods employed for comparison in the studies on this topic. The purpose of the present paper is threefold: (1) to describe what methodological problems are recognized in previous contrastive studies on the perspectives, especially in the field of cognitive linguistics; (2) in order to avoid methodological problems, to propose an alternative method for a more objective comparison of the perspectives between two languages; and (3) to demonstrate the validity of the proposed method for contrasting formulation patterns in terms of their perspective by some of the data obtained.
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Nishijima, Yoshinori ; 西嶋, 義憲
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金沢大学人間社会研究域経済学経営学系<br />The present paper discusses the different perspectives from which Japanese and German speakers f
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ormulate utterances. It was hypothesized that these different perspectives are reflected not only in evaluating concepts of communicative behavior, but also in routine formulas for controlling communicative behavior in Japanese and German. This hypothesis was examined by comparing two pairs of functionally equivalent routine formulas in Japanese and German. Furthermore, a questionnaire was administered to compare other Japanese and German routine formulas possibly used in corresponding situations. The results confirmed that in Japanese, linguistic formulation patterns relate to the empathy felt by the speaker toward an interlocutor, arising from the perspective of their situation, whereas in German, these tend to depend on an opposition between the participants involved, characterized by a perspective external to their situation. Because the data employed in the present study are limited, the hypothesis should be verified using extensive data. The results of this study helps clarify the possible misunderstandings between Japanese and German speakers, owing to the different linguistic formulation patterns employed, and could promote more efficient foreign language teaching.
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Nishijima, Yoshinori ; 西嶋, 義憲
概要:
金沢大学人間社会研究域経済学経営学系<br />Research on the perspectives from which linguistic expressions are formulated has increased in t
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he past 20 years due to the development of cognitive linguistics. For example, Ikegami (2000) showed that Japanese and English speakers employ different perspectives by comparing the opening sentence of a Japanese literary text with its English translation. Similarly, Narita (2009) compared sentences from literary texts with their translations in Japanese and German. However, these studies analyzing literary text translations contain little discussion on the validity of the translation-based comparison method, particularly in terms of comparability and objectivity. This paper has three purposes: (1) to claim that the original and translation-based methods are not always appropriate for perspective studies; (2) to propose, as an alternative method, comparing functionally equivalent formulas used on public signs, i.e., Watch your step, Keep out, and Out of Service; and (3) to show how Japanese differs from German in the perspectives from which corresponding expressions in the two languages are formulated. Expressions were collected from signs on buses, trains, and railway stations in Japan and Germany. Examples include Haire-masen/Kein Eingang (‘No entrance’), Senro-ni orite-wa ike-masen/Ausstieg verboten (‘Do not go down to the railway track’), and ishitsubutsu-gakari/Fundbüro (‘Lost and found’). Functionally equivalent expressions were selected for the analysis. For example, a formula telling bus passengers that the bus will stop at the next station is Tsugi tomari-masu (next.TOP stop.HON) in Japanese and Wagen hält (vehicle.NOM stop.PRES) in German. These corresponding expressions can be compared syntactically and semantically. The former has no surface-level subject; it conveys that “I” and “we” or the bus will stop at the next station. The scene is described from the perspective inside the situation, i.e., from within the bus. The latter has a third-person subject, Wagen, signifying that the bus is observed from the perspective outside the situation. These different perspectives and their occurrence distributions are shown through the comparison of corresponding sign expressions. The analysis reveals that Japanese tends to formulate expressions from a perspective inside the scene where the event occurs, whereas German expresses sentences from the perspective outside the scene.<br />19th International Congress of Linguists(19 ICL), 21-27 July 2013 Geneva
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西嶋, 義憲 ; Nishijima, Yoshinori
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金沢大学人間社会研究域経済学経営学系<br />異なる言語間の対応する言語表現を比較する場合，どのようにすればより客観的で妥当な比較が可能になるのかを考察する．従来，言語間の比較の際，とくに認知言語学分野では翻訳を利用する研究が多く見られた
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．しかしながら，翻訳を用いた比較は比較可能性という観点から問題がないわけではない．その問題点を確認し，それとは異なる新たな比較方法を提案し，それによる成果を紹介する．<br />The aim of this study is to consider the possibility of a more objective comparison of equivalent expressions of two languages. In comparing linguistic expressions of two languages, especially in cognitive linguistics, translations have been often used. However, comparisons using translations can be problematic. In this study, problems of translation-based comparison are discussed and a new method for a more objective linguistic comparison of two languages is proposed. Some results of the studies based on this method are also described as case studies.
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Mukaida, Naofumi ; Nakamoto, Yasunari ; 向田, 直史 ; 中本, 安成
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金沢大学がん進展制御研究所<br />Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen
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presenting cells (APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppressive molecules and cells to dampen tumor immunity. Moreover, the liver microenvironment exhibits immune tolerance to reduce aberrant immune responses to massively-exposed antigens via the portal vein, and immune dysfunction is frequently associated with liver cirrhosis, which is widespread in hepatocellular carcinoma (HCC) patients. Immune therapy aims to reduce tumor burden, but it is also expected to prevent non-cancerous liver lesions from progressing to HCC, because HCC develops or recurs from noncancerous liver lesions with chronic inflammatory states and/or cirrhosis and these lesions cannot be cured and/or eradicated by local and/or systemic therapies. Nevertheless, cancer immune therapy should augment specific tumor immunity by using two distinct measures: enhancing the effector cell functions such as antigen presentation capacity of APCs and tumor cell killing capacity of cytotoxic cells, and reactivating the immune system in immune-suppressive tumor microenvironments. Here, we will summarize the current status and discuss the future perspective on immune therapy for HCC. © The Author(s) 2018.<br />Supported by (in part) Research Programs on the Innovative Development and Application for New Drugs for Hepatitis B (No. 17fk0310116h0001) from the Japan Agency for Medical Research and Development (AMED) and Extramural Collaborative Research Grant of Cancer Research Institute, Kanazawa University.
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佐無田, 光
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渡會, 兼也 ; 酒井, 佑士 ; Watari, Kenya ; Sakai, Yuji
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金沢大学附属高等学校<br />タブレット端末の音センサーでピンポン玉の反発係数を測定した結果を紹介する。この方法は従来の距離を測定する方法よりも簡易であること，距離の測定が最初の1回で済むこと，などの利点がある。体育館などでのボールの反発
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係数を見積もるのに役立つ可能性がある。
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藤澤, 美恵子 ; 竹村, 和久 ; 船木, 由喜彦 ; 高橋, 遼 ; Fujisawa, Mieko ; Takemura, Kazuhisa ; Funaki, Yukihiko ; Takahashi, Ryo
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金沢大学人間社会研究域経済学経営学系<br />CO2削減に向けて政府は，エネルギーラベルによる建物のエネルギー使用量の表示制度を整備予定である．本研究ではこのラベルが，消費者にどう認識され，CO2削減に至る省エネ誘導ができるのかに焦点を当
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て，ラベルへの評価等の調査をおこなった．クロス集計の結果，2型あるエネルギーラベルのうちタコメータ型の方がABC型に比較して混同する比率が高くわかりにくい反面，省エネ誘導は優れていることが明らかになった．省エネ誘導は，ラベルに表示される基準レベルを増やすより，判断の参考となる参照点を上昇させる場合に効果が大きいことがわかった．ロジスティック回帰分析から，環境への関心度が高い消費者や寒冷地居住者は省エネ誘導されやすい傾向にあるが，無職やABC型を先に回答した者は逆の反応を示すことが確認できた．ABC型を先に回答したことが省エネ誘導に負の影響があることから，タコメータ型の方が省エネ誘導しやすいことが分析結果からも示唆された．
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藤澤, 美恵子 ; Fujisawa, Mieko
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金沢大学人間社会研究域経済学経営学系
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Mukai, Kanae ; Komatsu, Emi ; Nakajima, Yukari ; Urai, Tamae ; Nasruddin ; Sugama, Junko ; Nakatani, Toshio ; 向井, 加奈恵 ; 中島, 由加里 ; 須釜, 淳子 ; 中谷, 壽男
概要:
金沢大学医薬保健研究域保健学系<br />Cutaneous wound healing is delayed by protein malnutrition (PM). On the other hand, estrogen promot
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es cutaneous wound healing by its anti-inflammatory and cell proliferation effects. Therefore, we hypothesized that estrogen administration in protein-malnourished ovariectomized (OVX) female mice might improve the inflammatory response and promote cutaneous wound healing as well as normal nutrition. To test this hypothesis, we used full-thickness excisional wounds in Control SHAM, PM SHAM, PM OVX and PM OVX+17β-estradiol mice. The Control diet included 200 g/kg protein and the PM diet included 30 g/kg protein. The ratio of wound area in the Control SHAM group was significantly smaller than those in the three PM groups. In addition, microscopic findings also showed that the ratio of collagen fibers, the ratio of myofibroblasts and the number of new blood vessels in the Control SHAM group were significantly greater than those in the three PM groups. However, the number of Ym1-positive cells as an anti-inflammatory M2-like macrophage marker in the PM OVX+17β-estradiol group was significantly higher than those in the other three groups. These results indicate that the appearance of anti-inflammatory M2-like macrophages was promoted by estrogen administration; however, it could not promote cutaneous wound healing upon a low-protein diet. Therefore, it may be confirmed that nutrition is more important for promoting cutaneous wound healing than estrogen administration.
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木森, 佳子 ; 須釜, 淳子 ; 中谷, 壽男 ; 福田, 汐里 ; 宮地, 利明 ; 紺家, 千津子 ; 大桑, 麻由美 ; 真田, 弘美 ; Kimori, Keiko ; Sugama, Junko ; Nakatani, Toshio ; Fukuda, Shiori ; Miyati, Toshiaki ; Konya, Chizuko ; Okuwa, Mayumi ; Sanada, Hiromi
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金沢大学医薬保健研究域保健学系<br />末梢静脈内カテーテル留置法では，対象静脈が目視困難な場合，確実な穿刺，合併症の発生に影響を及ぼす．本研究の目的は目視困難静脈の穿刺技術向上に向け，目視の可否による血管径 ・ 深さ，動脈との位置関係を
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超音波診断装置で，皮膚色を色差計で計測し違いを明らかにすることである．研究デザインは実態調査型研究である．対象者は健常若年女性 20名，計測静脈は 58本，計測動脈は 18本であった．その結果，目視の可否に有意差があったのは深さのみで，血管径，動脈との位置関係，皮膚色は同等であることが明らかになった．静脈の深さの平均 (SD) は，目視可能静脈が2.7 (0.7) mm，目視困難静脈が4.6 (1.8) mmであった (p=.0001)．目視の可否の分離値は 3.0mm (AUC=0.919，95％CI 0.84－0.99)で，深さ3mm以上の留置カテーテル用末梢静脈は目視困難になることが明らかとなった．したがって，目視困難な静脈は深さ3mm以上の穿刺技術が，動脈穿刺の防止は，目視の可否に関わらない穿刺技術の必要性が示唆された．<br />During catheter placement, peripheral intravenous access is affected by the visibility of the vein, such that the risk of peripheral nerve injuries and arterial punctures, increases as the visibility decreases. This study examined the relation between vein visibility and (a) vein width, (b) vein depth, (c) position of the artery relative to the vein, and (d) skin color. This was an observational study with prospective data collection. A total of 20 healthy young women (58 veins and 18 arteries) were examined. As a result, vein visibility demonstrated significant differences in relation to vein depth, but not in relation to the other three factors. The mean depth (SD) was 2.7 (0.7) mm for visible veins and 4.6 (1.8) mm for invisible veins (p=0.0001). The cut off point was 3.0 mm (AUC=0.919 95％ CI-0.84 to 0.99), indicating that peripheral veins for catheter placement are more likely to be invisible when the depth is 3.0 mm or more. These findings highlight the need for two kinds of venipuncture skills : those for invisible veins with a depth of 3.0 mm or more, and those that will prevent arterial puncture regardless of vein visibility.
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小松 , 俊文 ; 前川, 匠 ; 重田, 康成 ; 高橋, 修 ; 田中, 源吾 ; Dang T., Huyen ; Komatsu, Toshifumi ; Maekawa, Takumi ; Shigeta, Yasunari ; Tanaka, Gengo
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金沢大学国際基幹教育院GS教育系
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田中, 源吾 ; Tanaka, Gengo
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金沢大学国際基幹教育院GS教育系
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田中, 源吾 ; Tanaka, Gengo
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金沢大学国際基幹教育院GS教育系<br />The Light-Switch Hypothesis' proposed by Parker (2003) is reviewed on the basis of recent relevant
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literature in order to test the hypothesis. This review revealed the following: 1) Diversification of bilaterian animals occurred during the Late Ediacaran Period, based on paleontological and molecular clock evidences. 2) Developmental genetic studies of eyes suggest that the eyes of bilaterian animals were formed from those of the Urbilateria, which hypothetically had both rhabdom and cilium photoreceptors during the Ediacaran period. During evolution, vertebrates utilized cilium photoreceptors, while invertebrates selected rhabdom photoreceptors for the development of eyes. On the basis of the detailed research of the ommatidium surface of the low-light adapted compound eye of the fruit fly, the phenotype of corneal nipple protuberances has changed in a extremely short time period from the view point of the geologic time scale. 3) The oldest fossilized eyes discovered are those of trilobite and bradoriid arthropods from 521 Ma. Increases in body size, and the corresponding increase of energy required, during 630Ma-521Ma may have been triggered by the evolution of the eye.
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前田, 晴良 ; 上田, 直人 ; 西村, 智弘 ; 田中, 源吾 ; 野村, 真一 ; 松岡, 廣繁 ; Maeda, Haruyoshi ; Ueda, Naoto ; Nishimura, Tomohiro ; Tanaka, Gengo ; Nomura, Shin'ichi ; Matsuoka, Hiroshige
概要:
金沢大学国際基幹教育院GS教育系<br />高知県佐川地域に分布する七良谷層の模式層序周辺の泥質砂岩中から，最上部ジュラ系を示す2種類のアンモノイド化石を発見した．そのうちAspidoceras属は，テチス海地域の最上部ジュラ系から多産し，
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Hybonoticeras属は同地域のキンメリッジアン−チトニアン階境界付近を示準するタクサである．これらの化石の産出により，七良谷層は最上部ジュラ系（キンメリッジアン−チトニアン階）に対比される可能性が高い．この結論は放散虫化石層序とおおむね調和的である．これまで七良谷層は，上部ジュラ系−下部白亜系鳥巣層群の層序的下位にあたる地層と考えられてきた．しかし七良谷層から産出したアンモノイドの示す時代は，鳥巣層群産アンモノイドのレンジと明らかに重複し，アンモノイド化石からは両岩相層序ユニットの時代差は識別できない．したがって，今後，七良谷層と鳥巣層群の層序関係を再検討する必要がある．<br />The Naradani Formation is located to the south of the Torinosu Group in the Sakawa district of Kochi, southwest Japan, and consists of a linear, narrowly distributed series of marine clastic deposits that contain allochthonous limestone blocks. This formation was previously correlated to the Bajocian–Bathonian Middle Jurassic using brachiopods extracted from the limestone blocks, with later radiolarian correlations suggesting an Oxfordian–Kimmeridgian Upper Jurassic age. The formation has also been interpreted to underlie the Upper Jurassic–Lower Cretaceous Torinosu Group. However, the discovery of two stage-diagnostic aspidoceratid ammonoids, Aspidoceras sp. and Hybonoticeras sp., from muddy sandstones in the stratotype area of the Naradani Formation casts doubt on these previous interpretations. Aspidoceras was widespread during the latest Jurassic, and the presence of Hybonoticeras limits this short stratigraphic interval to the Kimmeridgian–Tithonian boundary in various Tethyan sections. This clearly suggests a latest Jurassic age for the Naradani Formation and generally supports the radiolarian biostratigraphy age-assignment. However, the ranges of ammonoids from the Naradani Formation overlap those from the Torinosu Group, meaning that it is not possible to determine an age-difference between these two lithostratigraphic units. Further research is needed to test other hypotheses, for example to determine whether heterotopic facies relationships exist between the Naradani Formation and the Torinosu Group.
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田中, 源吾 ; 伊丹, 美穂 ; 黒澤, 幸愛 ; 吉岡, あゆみ ; 横田, 麻莉 ; 新井, 理菜 ; 出原, 祐樹 ; 林, 広樹 ; Tanaka, Gengo ; Itami, Miho ; Kurosawa, Sachie ; Yoshioka, Ayumi ; Yokota, Mari ; Arai, Rna ; Idehara, Yuki ; Hayashi, Hiroki
概要:
金沢大学国際基幹教育院GS教育系<br />群馬県富岡市南西部の大島付近の鏑川沿いに分布する中部中新統富岡層群小幡層において‘古蛇崩い礁’と呼ばれる隣接地域とは岩相が著しく異なった地層が露出している．今回，微化石群集を用いて，当該地層の堆積
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年代と堆積環境の再検討を行った．介形虫化石および岩相解析の結果，‘古蛇崩い礁’は，漸深海の石英斑岩の海底面上に浅海からの堆積物重力流による流れ込みで形成された堆積物であることが明らかとなった．また有孔虫と介形虫化石から，当該地層は前期中新世後期〜中期中新世前期のいわゆる「中新世熱帯海中気候事件」期に堆積したものであることが判明した．本邦における「中新世熱帯海中気候事件」期の漸深海性介形虫化石群としては2例目の報告となる．<br />We present a micropaleontological re-examination of the depositional environment of the ‘Kojyakui-sho’ sediments of the Middle Miocene Obata Formation, part of the Tomioka Group, located along the Kabura-gawa River near Tajima, Tomioka City, western Gunma Prefecture, central Japan. These sediments contain sublittoral and bathyal ostracods, and were deposited in the bathyal zone on a quartz-porphyry bedrock seafloor during the late Early to early Middle Miocene. Planktonic foraminifera and ostracods within these samples indicate that the ‘Kojyakui-sho’ sediments formed during the Miocene Climatic Optimum; this is the second reported occurrence of these Miocene Climatic Optimum bathyal ostracod species in Japan.
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| 21.
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金子, 稔 ; 野村, 正弘 ; 田中, 源吾 ; Kaneko, Minoru ; Nomura, Masahiro ; Tanaka, Gengo
概要:
金沢大学国際基幹教育院GS教育系
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| 22.
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田中, 源吾 ; 森脇, 広 ; 永迫, 俊郎 ; 西澤, 文勝 ; 松島, 義章 ; 鈴木 ; Morikawa, Hiroshi ; Nagasako, Toshiro ; Nishizawa, Fumikatsu ; Matsushima, Yoshiaki ; Suzuki, Takehiko ; Tanaka, Gengo
概要:
金沢大学国際基幹教育院GS教育系<br />Shinjima (Moeshima) Island in Kagoshima Bay, southern Kyushu, Japan is noteworthy in volcanology,
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paleontology, and palaeo-environmental studies, because the island emerged from the bay bottom during volcanic activity at Sakurajima in 1780 AD. As a result, Holocene and late-Pleistocene deposits of the bay including muddy deposits, a thick pyroclastic flow deposit, and prominent molluscan shell beds occur on this island. Several tephras included in the bay deposits are critical for deriving their precise chronology. The chronology of those tephras was constructed on the basis of their identification using both refractive indices and major element compositions of constituent glass shards, as well as stratigraphic features in the field. Tephras identified in sediments from younger to older are Sakurajima-Taisho (Sz-Ts)-/P1, Sakurajima-Sueyoshi(Sz-Sy)-/P11, Yonemaru, Sakurajima-Uwaba(Sz-Ub)-/P12, Sakurajima-Takatoge3 (Sz-Tk3)-/P13, Sakurajima-Satsuma (Sz-S)-/P14, and Shinjima pyroclastic flow deposit. The Shinjima pyroclastic flow deposit, which differs stratigraphically between northern and southern areas of Shinjima Island, is the same tephra in the two areas, and is estimated to be c. 13,000 cal BP in age. The pumice clasts of Sz-Sy/P11 provided a suitable environment for the habitat of a prominent shell bed (Moeshima Shell Bed) composed mainly of Neopycnodonte musashiana. Sz-Ub/P12, Sz-Tk3/P13, and associate secondary deposits of Sz-S/P14 indicate that the deposit was formed in the last 13,000 cal BP. The chronology of the deposits of Shinjima Island is based on the findings of stratigraphic positions and ages of those tephras, and 14C ages obtained in this study, and will play an important role when examining the palaeo-environmental history of Kagoshima Bay since the last deglaciation.
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| 23.
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Tanaka, Gengo ; Nakase, Hajime ; Yamashita, Shota ; Arai, Kazuno ; 田中, 源吾
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金沢大学国際基幹教育院GS教育系<br />In Rikuzentakata City, Ostracode assemblages in sediment deposited by the Tohoku‐Oki earthquake an
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d tsunami of 11 March 2011 revealed that the sediment was derived from the seafloor from at least 9 m water depth, and was transported inland more than 1 km. The tsunami wave height at this location was higher than 10 m. Four hundred fifty seven modern ostracode assemblages were used in the modern analogue technique to estimate the depth source of the tsunami deposited assemblages. The application of this method to paleo‐tsunami deposits may provide insight into past tsunami wave height and potentially earthquake slip and magnitude.<br />Embargo Period 6 months
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| 24.
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Tanaka, Gengo ; Parker, Andrew R. ; Hasegawa, Yoshikazu ; Siveter, David J. ; Yamamoto, Ryoichi ; Miyashita, Kiyoshi ; Takahashi, Yuichi ; Ito, Shosuke ; Wakamatsu, Kazumasa ; Mukuda, Takao ; Matsuura, Marie ; Tomikawa, Ko ; Furutani, Masumi ; Suzuki , Kayo ; Maeda, Haruyoshi ; 田中, 源吾
概要:
金沢大学国際基幹教育院GS教育系<br />Vision, which consists of an optical system, receptors and image-processing capacity, has existed
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for at least 520 Myr. Except for the optical system, as in the calcified lenses of trilobite and ostracod arthropods, other parts of the visual system are not usually preserved in the fossil record, because the soft tissue of the eye and the brain decay rapidly after death, such as within 64 days and 11 days, respectively. The Upper Carboniferous Hamilton Formation (300 Myr) in Kansas, USA, yields exceptionally well-preserved animal fossils in an estuarine depositional setting. Here we show that the original colour, shape and putative presence of eumelanin have been preserved in the acanthodii fish Acanthodes bridgei. We also report on the tissues of its eye, which provides the first record of mineralized rods and cones in a fossil and indicates that this 300 Myr-old fish likely possessed colour vision.<br />This work was supported by the Science Research of Education and Science Government of Japan (grant no. 24540501 to G.T. and no. 24340129 to H.M.).
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| 25.
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田崎, 和江 ; 田崎, 史江 ; 奥野, 正幸 ; 竹原, 照明 ; 石垣, 靖人 ; 中川, 秀昭 ; Tazaki, Kazue ; Tazaki, Fumie ; Okuno, Masayuki ; Takehara, Teruki ; Ishigaki, Yasuhito ; Nakagawa, Hideki
概要:
金沢大学理工研究域地球社会基盤学系<br />イタリア・トスカーナ州南部のマレンマという地域には，イオウ臭が強くpH7，水温37°Cの棚田状のサトゥルニア天然温泉がある．本研究では，サトゥルニア天然温泉で産出される，豆石，褐色石灰岩および緑
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色バイオマットについて，化学組成，鉱物組成，微生物的特徴を調べた．全岩試料のXRD分析により，豆石は方解石，自然硫黄，石英から構成されており，褐色石灰岩は雲母，自然硫黄，菱沸石，7 Å粘土鉱物から構成されていることを明らかにした．また，全岩試料のXRF分析により，褐色石灰岩にはO，Si，Al，K，Ca，Fe，Naが多く，豆石にはC，O，Ca，Sr，Sが多いことを明らかにした．更に，豆石の断面をSEM-EDSで観察・分析・元素濃度分布図を行ったところ，全岩試料のXRDおよびXRF分析では検出されなかった微生物とSrを含むフランボイダル黄鉄鉱や燐灰石が発見された．<br />A well-known terrace-forming hot spring is located at Saturnia in the Maremma area of southern Toscana, Italy. The waters are circumneutral (pH around 7), mesophilic (around 37°C), and give off a strong sulfurous odor. Pisoliths, brown limestone, and green microbial mats are found in the area. Hot spring structures and compositions are determined based on mineralogical and chemical data obtained with a powder X-ray diffractometer (XRD) and an X-ray fluorescence analyzer (XRF). Microbial parameters are determined on sub-millimeter scales using a scanning electron microscope, equipped with an energy-dispersive X-ray spectrometer (SEM-EDS).XRD results indicate that the pisoliths are composed of calcite, native sulfur, and quartz, whereas the brown limestone contains mica, native sulfur, chabazite, and 7 Å clay minerals. XRF analysis indicates that the pisoliths contain mainly C, O, Ca, S, Si, and Sr, whereas the brown limestone contains high concentrations of O, S, Al, K, Ca, Fe, and Na. Because the pisoliths are Ca-rich, concentrations of heavy metals (Sr, Sn, and Pb) at the aqueous interface can be explained by combining XRF chemistry, XRD mineralogy, and SEM-EDS observations of green microbial mats. SEM-EDS elemental maps of the pisolith indicate the presence of apatite and framboidal pyrite crystals.
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| 26.
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田崎, 和江 ; 竹原, 照明 ; 橋田, 由美子 ; 橋田, 省三 ; 中村, 圭一 ; 横山, 明彦 ; 青木, 小波 ; 田崎, 史江 ; Tazaki, Kazue ; Takehara, Teruaki ; Hashida, Yumiko ; Hashida, Shozo ; Nakamura, Keiichi ; Yokoyama, Akihiko ; Aoki, Conami ; Tazaki, Fumie
概要:
金沢大学理工研究域地球社会基盤学系<br />黒柿はカキノキ科の一つであり，幹・枝・根の断面に黒色の部分があり，心材や辺材には縞が美しい孔雀の羽根のような模様（孔雀杢 くじゃくもく）がある．孔雀杢は何百年と樹齢を重ね，かつ，様々な条件を満た
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した柿の木だけが黒と白の美しい模様を持つようになった希少な銘木である．材質が竪硬で粘りもあり，細かい細工をする指物に適しており和家具，茶道具などが金沢伝統工芸品となっている．しかし，江戸時代に加賀藩が黒柿の栽培を行っていたとされるものの，その科学的な記録はない．なぜ柿の木の幹に黒い色の美しい模様ができるのかを究明するために，石川県金沢市内に生育している黒柿を採取して，IP，XRD，ICP-MS，XRF，SEM-EDS，放射能測定器を用いて物理化学的，鉱物学的，微生物学的特徴を調べた．本研究試料の「黒柿」のXRD 分析では，セルロースの他に低温型α- クリストバライト，生体アパタイト（燐灰石），ハロイサイトなどの粘土鉱物が含まれていた．黒柿の黒色化した幹に形成する孔雀杢は“珪化木”ということができる．本研究結果から，①黒柿が“珪化木”になるには，まず，根の中心の白色部に認められた微生物がCa >>> P，S >> Mg > Si，Fe，Cl，K，Mn を取り込み，生体アパタイトを形成する．②成長するにしたがって，放射能核種やB，Br を伴って, さらにCa，P，S >> K，Mg，Si，Sr > Cl，Mn，Fe などの元素を取り込みながら黒色化する．③そして，年月を経るにしたがって, 幹の辺材部に黒色の縞模様（孔雀杢）を作りながら低温型α- クリストバライト（珪化木）を形成することが明らかになった．<br />Kurogaki (Black persimmon; Diospyros kaki) grows very slowly and has extremely hard wood known for its striking black coloration, referred to as the “peacock pattern”. It was formerly planted in Kanazawa, Ishikawa, Japan. Kurogaki is currently very rare, found in only one of every 1,000 to 10,000 trees. Therefore, scientific data on Kurogaki are currently very limited but these trees are highly valuable for manufacturing furniture, tea ceremony goods, boxes, and other miscellaneous articles.Here we report the characterization of Kurogaki at Kanazawa, Ishikawa, Japan, based on radioactivity, purple mineral light, and H2 O2 reactions in the field. To date, no report has described the results of electron microscopy observations and chemical analyses, which could elucidate simple identification of species. Here we studied the microstructure, mineralogy, chemical composition, and radioactivity associated with microorganisms in Kurogaki wood using analytical data based on X-ray diffraction (XRD), X-ray fluorescence (XRF), inductively coupled plasma-mass spectrometry (ICP-MS), imaging plate (IP), scanning electron microscopy equipped with energy dispersive spectroscopy (SEM-EDS), and semiconductor detectors. We investigated the distribution, location, identification, structure, and differentiation of the black “peacock pattern” parts and ordinarily colored wooden parts and roots.We evaluated the mineralogy, chemistry, and micromorphology of Kurogaki using a combination of micro techniques. Using XRD, the black “peacock pattern” parts were found to mainly comprise cellulose associated with spherical and beaded microorganisms, mineralized living apatite, α-cristobalite, and halloysite. Particular elements associated with microorganisms were identified using SEM-EDS, which revealed the elemental content maps of the central white spot in cross sections of the “peacock pattern”, indicating high concentrations of Ca, P and S. The chemical compositions of the black and white parts were determined based on mineralogical and chemical data obtained using XRF analyzer and ICP-MS.Furthermore, we used imaging plate methods to obtain radioactive images of the cross sections of the “peacock pattern”. The objective was to illustrate the association of minerals with various microorganisms that are capable of absorbing both radionuclides and stable isotopes from soil and water. A radio dosage analysis of the higher black parts was performed by imaging plate pictures. We investigated the quantitative radiation dosages of the “peacock pattern” using Ge and Si semiconductor detectors, which revealed 137Cs concentrations.The black “peacock pattern” parts were richer in almost all elements such as K, Ca, Mg, S, Al, Fe, P, Na, Mn, B and Ba, than the white cellulose parts, indicating a role of microorganisms in mediating the transfer of metal solutes from the hydrosphere and soils. Using SEM-EDS micromorphology, the chemical composition of the black “peacock pattern” parts was found to be associated with α-cristobalite and living apatite having wooden clapper-like microcrystals. The distribution of elements indicated the influences of soils in their surrounding environment. Our results provide the evidence of the ability of microorganisms to immobilize radionuclides in the soils. The microorganisms grow in the black “peacock pattern” parts of Kurogaki.In conclusion, α-cristobalite and living apatite crystals physically and biologically grow in the sap with cellulose under neutral conditions (pH7) in association with microorganisms using carbon dioxide supplied by bacteria. Therefore, the crystals produced the “peacock pattern” in Kurogaki were formed at late times during the year.
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| 27.
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田崎, 和江 ; 高橋, 正則 ; 鈴木, 祐恵 ; 井本, 香如 ; Tazaki, Kazue ; Takahashi, Masanori ; Suzuki, Sachie ; Imoto, Konyo
概要:
金沢大学理工研究域地球社会基盤学系
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| 28.
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田崎, 和江 ; 中野, 幹夫 ; 竹原, 照明 ; 石垣, 靖人 ; 中川, 秀明 ; Tazaki, Kazue ; Nakano, Mikio ; Takehara, Teruaki ; Ishigaki, Yasuhito ; Nakagawa, Hideaki
概要:
金沢大学理工研究域地球社会基盤学系<br />2011年3月11日に発生した福島第一原発事故により放射能汚染した福島県南相馬市原町区馬場の農業用水にプラスチック製品を7ヶ月間浸して置いたところ,全9試料のうち3試料において放射線量の上昇が認
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められた.そのカーペット,PE防鳥網,荷造り用ひもの3種類について詳細な分析・観察を行った.特に,カーペットの繊維の放射線量が高く,ゲルマニウム半導体検出器による分析では,セシウム134とセシウム137が検出された.また,蛍光X線分析により,Rb,Sr,Nb,Pbも認められた.分析電子顕微鏡観察によれば,この繊維の表面には粘土の微粒子といっしょにケイソウが繁茂しており,Rb,Sr,Pbが濃集していた.放射能汚染した農業用水に浸したプラスチック繊維の表面にはケイソウが多数生息し,粘土の微粒子とともに放射性物質を吸着することが明らかになった.<br />After the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident on 11 March, 2011, the high radioactive dosage was found in polluted water for agriculture use at Baba, Haramachi, Minami-Soma, Fukushima Prefecture, Japan. Field experiment for decontamination of water had been studied by using commercial plastic materials. The agricultural water comes from Tetsuzan dam is full of radioactive-contaminated water. Experimental analysis showed that the plastic materials can take up radioactive elements for several months soaked in the polluted agricultural water. The quantitative analyses using X-ray fluorescence analysis, Ge semiconductor and scanning electron microscopy equipped with energy dispersive X-ray spectrometer (SEM-EDS), revealed the detection of the radionuclides on the plastic materials with diatom and clays. The results suggest the adsorption of radionuclides on the surface of plastic materials due to FDNPP accident. The plastic materials associated with clays and diatoms could be stronger carriers of radionuclides in the polluted water. Adherence of diatoms to the plastic fiber in the water for 7 months suggested that some plastic materials were taking up heavy metals (Zn, Ba, Pb, Sb) with radioactive elements (Cs etc.). Mechanisms by which radioactive pollutants and microorganisms are adsorbed onto and desorbed from clays at aqueous interface can be understood by combining chemical analysis with electron microscopy observation.
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| 29.
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佐藤, 和也 ; 田崎, 和江 ; 奥野, 正幸 ; 久保, 博 ; Satoh, Kazuya ; Tazaki, Kazue ; Okuno, Masayuki ; Kubota, Hiroshi
概要:
金沢大学理工研究域地球社会基盤学系<br />長野県の松代温泉は,大量のほう素(B)を含む温泉としてよく知られている.その排水溝には茶褐色および黒色のバイオマットが形成されている.特に河川水と温泉排水が交わる部分には黒色のバイオマットが形成
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されている.いずれのバイオマット中にも多量のBが濃集しており,これによって,排水中のB濃度は,排出直後よりも4割程度減少する.これは,バイオマット中に生息するシアノバクテリアがカルサイトを作る時に,二酸化炭素のかわりに炭酸塩イオンを取り込むからである.その際に細胞周辺に局所的に高アルカリ環境を作り出し,温泉中のHBO2を電離させ,よりBを他の物質に結合しやすい状態にするためである.シアノバクテリアはカルサイトを作り出すことによって,Bを濃集させ,温泉水中のBを軽減する働きがある.<br />Matsushiro Hot springs in Nagano Prefecture, Japan is known as one of the hot springs in which the concentration of boron (B) is quite high. The hot spring water drainage ditch was covered with dark brown microbial mats. Before the drainage meets the river, the microbial mats deposit is more than 2m in depth. The microbial mats deposit has two layers. In the upper parts, dark brown microbial mats covered the surface. Underneath are black microbial mats which make up a portion of the two layer structure. At the junction of the drainage and river water, only black microbial mats occurred. The aim of this study was to reduce the boron concentration of the drainage water with microbial mats at Matsushiro Hot Springs. ASS analysis showed that microbial mats collected from five different points contain 854mg B/kg, 8628mg Fe/kg, 120mg As/kg, and 912mg Mg/kg on average. ED-XRF analysis showed that all microbial mats contained more than 50wt% of Ca. XRD analysis and FT-IR spectra of the microbial mats indicated the presence of calcite. Observations by optical and electron microscopy showed that cyanobacteria inhabited dark brown microbial mats, whereas cyanobacteria and diatoms inhabited in black mierobial mats. Cyanobacteria use an enzyme named carbonate anhydrase (CA). HCO3- dissolved in the hot spring water was broken down into CO2 and OH- by CA. That OH- made temporary alkaline conditions around the cyanobacteria. Such alkaline conditions facilitate the break down of HBO2 into H+ and BO2-. BO2- can form many chemical compounds. The concentration of boron described in this study might have profound implications for bioremediation of boron contaminated sites.
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| 30.
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Kobayashi, Mio ; Kakuda, Yuko ; Harada, Kenichi ; Sato, Yasunori ; Sasaki, Motoko ; Ikeda, Hiroko ; Terada, Mitsuhiro ; Mukai, Munenori ; Kaneko, Shuichi ; Nakanuma, Yasuni ; 小林, 水緒 ; 原田, 憲一 ; 佐藤, 保則 ; 佐々木, 素子 ; 池田, 博子 ; 金子, 周一 ; 中沼, 安二
概要:
金沢大学医薬保健研究域医学系<br />AIM: To investigate histological and immunohistochemical differences in hepatitis between autoimmune
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hepatitis (AIH) and primary biliary cirrhosis (PBC) with AIH features. METHODS: Liver needle biopsies of 41 PBC with AIH features and 43 AIH patients were examined. The activity of periportal and lobular inflammation was scored 0 (none or minimal activity) to 4 (severe), and the degree of hepatitic rosette formation and emperipolesis was semiquantatively scored 0-3. The infiltration of mononuclear cells positive for CD20, CD38, CD3, CD4, and CD8 and positive for immunoglobulins (IgG, IgM, and IgA) at the periportal areas (interface hepatitis) and in the hepatic lobules (lobular hepatitis) were semiquantitatively scored in immunostained liver sections (score 0-6). Serum aspartate aminotransferase (AST), immunoglobulins, and autoantibodies at the time of liver biopsy were correlated with the histological and immunohistochemical scores of individual lesions. RESULTS: Lobular hepatitis, hepatitic rosette formation, and emperipolesis were more extensive and frequent in AIH than in PBC. CD3+, CD4+, and CD8+ cell infiltration scores were higher in the hepatic lobules and at the interface in AIH but were also found in PBC. The degree of mononuclear cell infiltration correlated well with the degree of interface and lobular hepatitis in PBC, but to a lesser degree in AIH. CD20+ cells were mainly found in the portal tracts and, occasionally, at the interface in both diseases. Elevated AST correlated well with the hepatocyte necroinflammation and mononuclear cell infiltration, specifically CD38+ cells in PBC. No correlation existed between autoantibodies and inflammatory cell infiltration in PBC or AIH. While most AIH cases were IgG-predominant at the interface, PBC cases were divided into IgM-predominant, IgM/IgGequal, and IgG-predominant types, with the latter sharing several features with AIH. CONCLUSION: These results suggest that the hepatocellular injuries associated with interface and lobular hepatitis in AIH and PBC with interface hepatitis may not be identical. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
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Okazaki, Mitsuyoshi ; Makino, Isamu ; Kitagawa, Hirohisa ; Nakanuma, Shinichi ; Hayashi, Hironori ; Nakagawara, Hisatoshi ; Miyashita, Tomoharu ; Tajima, Hidehiro ; Takamura, Hiroyuki ; Ohta, Tetsuo ; 岡崎, 充善 ; 牧野, 勇 ; 北川, 裕久 ; 中沼, 伸一 ; 林, 泰寛 ; 中川原, 寿俊 ; 宮下, 知治 ; 田島, 秀浩 ; 高村, 博之 ; 太田, 哲生
概要:
金沢大学医薬保健研究域医学系<br />We herein report a case of anaplastic carcinoma of the pancreas with remarkable intraductal tumor gr
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owth into the main pancreatic duct. A 76-year-old male was referred to our hospital for treatment of a pancreatic tumor. Preoperative examinations revealed a poorly defined tumor in the main pancreatic duct in the body of the pancreas, accompanied with severe dilatation of the main pancreatic duct, which was diagnosed as an intraductal papillary-mucinous neoplasm. We performed distal pancreatectomy and splenectomy. The pathological examination revealed that the tumor consisted of a mixture of anaplastic carcinoma (giant cell type) and adenocarcinoma in the pancreas. There was a papillary projecting tumor composed of anaplastic carcinoma in the dilated main pancreatic duct. The patient is now receiving chemotherapy because liver metastasis was detected 12 mo after surgery. In this case, we could observe a remarkable intraductal tumor growth into the main pancreatic duct. We also discuss the pathogenesis and characteristics of this rare tumor with specific tumor growth. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
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| 32.
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Sato, Hirohide ; Sato, Yasunori ; Harada, Kenichi ; Sasaki, Motoko ; Hirano, Katsuyasu ; Nakanuma, Yasuni ; 佐藤, 保則 ; 原田, 憲一 ; 佐々木, 素子 ; 中沼, 安二
概要:
金沢大学医薬保健研究域医学系<br />A 77-year-old woman complained of epigastralgia, and a tumor (5 cm in diameter) of the gallbladder n
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eck was detected by image analysis. Following cholecystectomy, the tumor was pathologically diagnosed as intraductal papillary neoplasm (IPN), gastric type, with associated invasive carcinoma. About 10 mo later, intraluminal multiple masses (3 foci, up to 1.8 cm) were noted in the extrahepatic bile duct, and the resected specimen showed that all tumors had similar gross and microscopic features as seen in gallbladder IPN without invasion, and they were synchronous multiple lesions. This case showed a papillary tumor of the gallbladder of gastric phenotype, and confirmed that the gallbladder is a target of IPN in addition to the bile ducts. © 2013 Baishideng. All rights reserved.
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Onishi, Ichiro ; Kitagawa, Hirohisa ; Harada, Kenichi ; Maruzen, Syogo ; Sakai, Seisyo ; Makino, Isamu ; Hayashi, Hironori ; Nakagawara, Hisatoshi ; Tajima, Hidehiro ; Takamura, Hiroyuki ; Fujimura, Takashi ; Kayahara, Masato ; Ikeda, Hiroko ; Ohta, Tetsuo ; Nakanuma, Yasuni ; 北川, 裕久 ; 原田, 憲一 ; 牧野, 勇 ; 林, 泰寛 ; 中川原, 寿俊 ; 田島, 秀浩 ; 高村, 博之 ; 藤村, 隆 ; 萱原, 正都 ; 池田, 博子 ; 太田, 哲生 ; 中沼, 安二
概要:
金沢大学医薬保健研究域医学系<br />We present the first case of an intraductal papillary neoplasm of the bile duct (IPNB) accompanying
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a mixed adenoneuroendocrine carcinoma (MANEC). A 74-yearold woman presented with fever of unknown cause. Laboratory data revealed jaundice and liver injury. Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bile duct, which exhibited early enhancement and papillary growth. Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater, characterized by its protruding and dilated orifice. Endoscopic ultrasonography visualized the polypoid tumor in the distal bile duct, but no invasive region was suggested by diagnostic imaging. Therefore, the initial diagnosis was IPNB. After endoscopic nasobiliary drainage, a pylorus-preserving pancreaticoduodenectomy was performed. Pathological examination of the resected bile duct revealed papillary proliferation of biliary-type cells with nuclear atypia, indicating pancreaticobiliary-type IPNB. In addition, solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident. Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component, diagnosing it as a neuroendocrine tumor (NET). Furthermore, the MIB-1 proliferation index of NET was higher than that of IPNB, and microinvasion of the NET component was found, indicating neuroendocrine carcinoma (NET G3). This unique case of MANEC, comprising IPNB and NET, provides insight into the pathogenesis of biliary NET. © 2013 Baishideng. All rights reserved.
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捶井, 達也 ; 小田, 誠 ; 田村, 昌也 ; 早稲田, 龍一 ; 松本, 勲 ; 渡邊, 剛 ; Tarui, Tatsuya ; Oda, Makoto ; Tamura, Masaya ; Waseda, Ryuichi ; Matsumoto, Isao ; Watanabe, Go
概要:
金沢大学医薬保健研究域医学系<br />症例は32歳，女性．乳房痛を自覚し，精査のため胸部造影CTを施行したところ後縦隔に均一な造影効果を伴う径3.1cmの腫瘤を認めた．右上肢からの静脈造影では造影剤が上大静脈から奇静脈弓へ逆行性に流入し，
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腫瘤が濃染した．これにより腫瘤を静脈瘤と診断した．血栓による肺血栓塞栓症や瘤の破裂の可能性を考え外科的切除の方針とした．手術は胸腔鏡下にて施行した．まず血栓の流出を防止するため奇静脈弓の上大静脈合流部を自動縫合器にて切離した．次に瘤に流入する肋間静脈と奇静脈本幹を結紮，切離し，血行を遮断したのち瘤を切除した．術後合併症はなく10日目に退院した．<br />The patient was a 32-year-old female with a chief complaint of mastodynia. A computed tomography (CT) scan incidentally presented a homogeneously enhanced tumor, 3.1 cm in diameter, in the posterior mediastinum. Venography by the right brachial vein showed retrograde flow from the superior vena cava to azygos vein in the early phase. In the delayed phase, pooling of contrast medium in the tumor was observed. Based on the above findings, the tumor was diagnosed as an azygos vein aneurysm. She underwent aneurysm resection under video-assisted thoracic surgery (VATS) due to the risk of pulmonary thrombosis and rupture of the aneurysm. Initially, the proximal end of the azygos vein was resected due to the risk of pulmonary embolism, and, then, three intercostal veins and the distal end of the azygos vein were resected. Finally, after complete blockage of the azygos vein, the aneurysm was resected. The patient followed an uneventful postoperative course, and was discharged on the 10th postoperative day without complication.
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古山, 和憲 ; 松本, 勲 ; 吉田, 周平 ; 懸川, 誠一 ; 竹村, 博文 ; Koyama, Kazunori ; Matsumoto, Isao ; Yoshida, Shunhei ; Kakegawa, Seichi ; Takemura, Hirofumi
概要:
金沢大学医薬保健研究域医学系<br />症例は49歳，男性．髄膜炎様症状のため当院神経内科へ紹介となった．胸部CTで左肺上葉肺門部に大きさ2.1 cmの不整形結節を認め，気管支鏡検査を行ったが確定診断に至らなかった．肺癌も否定できない画像所
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見のため外科的肺生検目的に当科紹介となった．手術は左肺上葉切除術を施行し，病理学的診断で肺クリプトコッカス症と診断された．術前の髄液検査ではクリプトコッカス抗原，培養検査ともに陰性であったが，術前の保存血液検体からクリプトコッカス抗原が検出されたため，髄膜炎様症状もクリプトコッカス症に伴うものと考え，抗真菌薬による治療を行った．症状は速やかに改善し，術後2年の現在，再発なく経過している．肺クリプトコッカス症は画像所見だけでは鑑別が難しく，診断に難渋する場合が多いが，切除生検が診断に有用であると考えられた．<br />A 49-year-old man was admitted to the Department of Neurological and Internal Medicine of our hospital with mild fever and headache, suggestive of meningitis. Computed tomography (CT) showed an approximately 2.1-cm- diameter nodule in the hilum of the left lung. He underwent bronchoscopy, but no diagnosis was made. Because the CT image led to a suspicion of lung cancer, he was referred to our department for diagnosis by therapeutic resection. Left upper lobectomy was performed. Histopathological examination of the resected specimen resulted in a diagnosis of pulmonary cryptococcosis. His cerebrospinal fluid (CSF) was negative for cryptococcal antigen and Cryptococcus neoformans was not grown on mycological culture of the CSF. However, a preserved preoperative blood sample was positive for cryptococcal antigen. Thus, cryptococcal meningitis was diagnosed and he was treated with antifungal therapy, which resulted in marked improvement of his fever and headache. There was no recurrence during the following 2 years. It is difficult to diagnose pulmonary cryptococcosis because the imaging findings vary markedly. We present a patient with pulmonary cryptococcosis diagnosed by resection of the affected lobe of the lung.
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西田, 沙貴 ; 小田, 誠 ; 松本, 勲 ; 田村, 昌也 ; 早稲田, 龍一 ; 渡邊, 剛 ; Nishida, Saki ; Oda, Makoto ; Matsumoto, Isao ; Tamura, Masaya ; Waseda, Ryuichi ; Watanabe, Go
概要:
金沢大学医薬保健研究域医学系<br />症例は59歳，女性．3年前に子宮体癌を疑われ準広汎子宮全摘術，S状結腸切除術を施行された．病理診断および精査の結果，原発性肺腺癌の腹腔内転移と診断された．その後の経過で，計6レジメンの化学療法と計10
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0Gyの放射線治療が施行された．転移巣の制御は良好であったが，原発巣の増大傾向を認めたため，手術目的に当科紹介となった．手術は，肺門部において，肺動脈および上葉気管支と周囲組織との強固な癒着を認めたため，これらを一括して鉗子にてクランプした後に切離し，断端を3-0vicryl糸にて縫合して閉鎖した．断端は有茎傍心膜脂肪織にて被覆した．術後の病理診断で，低分化肺腺癌と診断された．術後さらに補助化学療法を追加し，術後9ヵ月間再発転移は認めていない．高容量化学放射線療法による炎症にて肺門部の処理が困難な症例に対しては，肺門部一括処理および有茎傍心膜脂肪織による気管支・肺動脈切離断端の被覆が有用であると考える．<br />A 59-year-old female was referred to our hospital for stage IV (cT3N2M1b) adenocarcinoma of the right lung. At the age of 56, at another hospital, she had undergone extended hysterectomy and resection of the sigmoid colon for suspected endometrial carcinoma and had received a diagnosis of lung adenocarcinoma based on pathological findings, a CT scan, and other examinations. A total of six regimens of chemotherapy and radiotherapy with a total dose of 100 Gy had been performed over 3 years, but it was resistant. Therefore, she was referred to our hospital to consider surgical treatment. We performed a right upper lobectomy because the tumor was localized and no other metastatic lesion was found. We ablated the tumor from the chest wall because it grew to the apical chest wall. In the hilum of the lung, individual ligation and closure of the pulmonary vessels and bronchus was found to be impossible because they tightly adhered to the peripheral tissue. Therefore, the hilar vessels and bronchus were clamped and cut in one mass. Their stumps were oversewn with 3-0 vicryl and covered with a pedicled pericardial flap. The post operative course was favorable, and the patient underwent adjuvant chemotherapy at the hospital that had originally referred her to us. She was free of clinically evident recurrence 9 months after treatment. We suggest that the mass closure of the hilar vessels and bronchus and covering the stumps with a pedicled pericardial flap are useful for cases in which it is difficult to individually close the vessels and bronchus due to ligneous scarring caused by radiation.
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中沼, 伸一 ; 萱原, 正都 ; 中川原, 寿俊 ; 伊藤, 博 ; 田島, 秀浩 ; 藤田, 秀人 ; 北川, 裕久 ; 藤村, 隆 ; 太田, 哲生 ; Nakanuma, Shinichi ; Kayahara, Masato ; Nakagawara, Hisatoshi ; Ito, Hiroshi ; Tajima, Hidehiro ; Fujita, Hideto ; Kitagawa, Hirohisa ; Fujimura, Takashi ; Ohta, Tetsuo
概要:
金沢大学附属病院肝胆膵・移植外科<br />症例は30歳の男性で，体重120 kg，BMI 41の高度肥満であった．重症急性膵炎と診断され当院に紹介された．CTでは両側胸水，膵実質の不明瞭化，後腎傍腔に及ぶ滲出液が認められた（Grade I
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V）．また，SIRS，急性循環不全の状態であった．入院後4病日，炎症反応の持続とCTにて膵頭部の血流障害が認められ，感染性膵壊死と判断し，necrosectomyを行った．腸管・組織浮腫のため，閉腹によるabdominal compartment syndromeが危ぐされたため，術後zipper techniqueとして衣類圧縮用袋を腹壁に固定し，腹腔内洗浄を伴うplanned necrosectomyを継続し，残存膵壊死組織の除去を行った．退院1年目の現在，患者は職場復帰している．衣類圧縮用袋を用いたzipper techniqueは高度肥満を有する感染性膵壊死の術後に有用な処置と考えられ若干の文献を加え報告する．<br />A severely obese 30-year-old male (BMI 41) weighing 120 kg and referred based on a diagnosis of severe acute pancreatitis was found in computed tomography (CT) to have bilateral hydrothorax, unclear pancreatic parenchyma, and exudate spreading to the posterior pararenal spacer (Grade IV). He also had SIRS and acute circulatory failure. On hospital day 4, persistent inflammatory reactions and a CT finding of pancreatic-head necrosis were noted. Based on a diagnosis of infectious pancreatic necrosis, he underwent necrosectomy. It was difficult to close the abdominal wall because of intestinal and tissue edema. Postoperatively, we attached a vacuum storage bag to the abdominal wall by a zipper. The planned necrosectomy, accompanied by intraperitoneal lavage, was continued to remove residual pancreatic necrotic tissue. No sign of abdominal compartment syndrome was noted. The patient has been discharged and resumed his previous work. The zipper technique and vacuum storage bag thus proved useful in providing postoperative care to a patient with infectious pancreatic necrosis accompanied by severe obesity.
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Nakanuma, Shinichi ; Miyashita, Tomoharu ; Hayashi, Hironori ; Tajima, Hidehiro ; Takamura, Hiroyuki ; Makino, Isamu ; Oyama, Katsunobu ; Nakagawara, Hisatoshi ; Fushida, Sachio ; Ohta, Tetsuo ; 中沼, 伸一 ; 宮下, 知治 ; 高村, 博之 ; 林, 泰寛 ; 田島, 秀浩 ; 牧野, 勇 ; 尾山, 勝信 ; 中川原, 寿俊 ; 伏田, 幸夫 ; 太田, 哲生
概要:
金沢大学附属病院肝胆膵・移植外科<br />Objectives: Continuous thrombocytopenia after liver transplant is associated with a less favorable
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prognosis, but this pathogenesis remains unclear. We focused on the consumption of platelets in the allograft. We assessed platelet consumption in allografts, and evaluated the pathology of platelet aggregation in an allograft tissue and its involve-ment in clinical outcomes.Materials and Methods: We took biopsy specimens from 20 patients. To examine the localization of platelet aggregation, CD42b was assayed immuno-histochemically, and its level of expression correlated with clinical data and outcomes.Results: Platelet aggregation in zone 3 was 70%, compared with 30% in zone 1 and 50% in zone 2. Platelets were found mainly as extravasated platelet aggregates in local microenvironments. Patients were stratified according to the extent of extravasated platelet aggregates in zone 3 into extravasated platelet aggregate-negative and -positive groups. Graft weight/recipient body weight ratio with the extravasated platelet aggregate-positive group was significantly lower than that of the extravasated platelet aggregate-negative group. Platelet count after surgery was lower, while total bilirubin and prothrombin time/international normalized ratio were higher in the extravasated platelet aggregate-positive than they were in the extravasated platelet aggregate-negative group.Conclusions: Extravasated platelet aggregates in the zone 3 of allograft tissue cause the consumption of platelets and continuous thrombocytopenia after transplant, and may be the clinical marker for deterioration of graft function. Platelet activation and degranulation following the release by platelets of some negative regulators may be involved partially in liver damage.
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Nakanuma, Shinichi ; Takamura, Hiroyuki ; Shoji, Masatoshi ; Hayashi, Hironori ; Tajima, Hidehiro ; Nakagawara, Hisatoshi ; Miyashita, Tomoharu ; Kitagawa, Hirohisa ; Tani, Takashi ; Ohta, Tetsuo ; 中沼, 伸一 ; 高村, 博之 ; 林, 泰寛 ; 田島, 秀浩 ; 中川原, 寿俊 ; 宮下, 知治 ; 北川, 裕久 ; 太田, 哲生
概要:
金沢大学附属病院肝胆膵・移植外科<br />Liver transplant is a treatment for familial amyloid polyneuropathy. Few cases of ABO-incompatible
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living-donor liver transplant for familial amyloid polyneuropathy exist. The outcome of an ABO-incompatible living-donor liver transplant has improved recently, using local infusion therapy and rituximab prophylaxis. Here, we describe a successful ABO-incompatible living-donor liver transplant in a patient with familial amyloid polyneuropathy in whom disease progression ceased at 2 years’ follow-up. Additionally, no evidence of acute or chronic rejection, or adverse events of the immuno-suppressive therapy, was seen. As a postoperative complication, fatty changes in the grafted liver because of malnutrition or adverse events of corticosteroids were confirmed by a liver biopsy taken early after transplant. The main cause of malnutrition was considered to be gastrointestinal dysfunction caused by familial amyloid poly-neuropathy. Therefore, before deterioration of digestive function, liver transplants should be considered for familial amyloid polyneuropathy. This case suggests that an ABO-incompatible living-donor liver transplant may provide greater opportunities for familial amyloid polyneuropathy patients.
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中沼, 伸一 ; 森, 和弘 ; 岩田, 啓子 ; 経田, 淳 ; 佐藤, 就厚 ; 安居, 利晃 ; Nakanuma, Shinichi ; Mori, Kazuhiro ; Iwata, Keiko ; Tsuneda, Atsushi ; Sato, Nariatsu ; Yasui, Toshiaki
概要:
金沢大学附属病院肝胆膵・移植外科<br />患者は70 歳，男性．腹部食道癌に対して胸腔鏡下食道亜全摘，胸骨後胃管再建，頸部吻合を施行した．第2 病日に右胸腔ドレーンより腸液色の排液を認め，CT，上部消化管透視にて胃管穿孔と診断し，再手術を
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行った．頸部吻合より肛門側約10 cm に胃管穿孔を認めた．胃管切除は手術侵襲が大きいと判断し，消化管内視鏡の先端を穿孔部へ通し，把持鉗子を腹腔内に進め，大網を把持して胃管内まで吊上げ，クリップにて胃壁に固定した．再手術後，ドレーン排液量は漸減し，穿孔部は再生組織に覆われた．食道癌術後胃管穿孔に対して胃管切除が選択できない場合，穿孔部の大網被覆と穿孔部周囲のドレナージは有効な場合もあると考えられたため，若干の考察を加えて報告する．<br />A 70 -year-old man underwent retrosternal gastric tube reconstruction following subtotal esophagectomyfor advanced abdominal esophageal cancer. On the second post-operative day, drained fluid changed to intestinaljuice. Computed tomography and gastrointestinal fluoroscopy showed perforation of the gastric tube. Wethen performed emergency surgery, and laparotomy was redone. During surgery, gastrointestinal endoscopydemonstrated gastric tube perforation at 10 cm from the anastomosis of stomach to cervical esophagus. Itwas too invasive to perform the resection of gastric tube, so we pulled the greater omentum into the stomachthrough the perforation site and fastened with clips（ omental patch method）. The drainage then graduallydecreased, and the perforation healed with regenerating epithelium. The omental patch method and drainageproved useful to treat gastric tube perforation following esophagectomy, and should be considered if resectionof the gastric tube is difficult.
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Saito, Motonobu ; Goto, Akiteru ; Abe, Noriko ; Saito, Katsuharu ; Maeda, Daichi ; Ohtake, Tohru ; Murakami, Yoshinori ; Takenoshita, Seiichi ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Cell adhesion molecule (CADM) genes encode immunoglobulin superfamily molecules, which are involved
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in cell-cell adhesion in a number of human epithelia. Through the maintenance of epithelia, CADM genes protect against malignant conversion and metastasis. Whilst numerous in vitro studies have investigated the molecular characteristics of CADM1 and CADM4 and in vivo studies have investigated CADM1 and CADM4 expression in a number of tumor types, the roles of CADM1 and CADM4 have yet to be elucidated. Therefore, in the present study, CADM1 and CADM4 expression levels were evaluated using immunohistochemistry staining in 208 patients with breast cancer and compared with clinicopathological factors. CADM1 and CADM4 expression levels were negative in 160 (76.9%) and 166 (79.8%) of the 208 cases, respectively. The lack of expression in these cases was associated with advanced tumor stage, suggesting that inactivation of CADM1 and CADM4 promotes breast cancer development. The prognostic role of CADM1 and CADM4 in breast cancer was also evaluated and the expression of CADM1 and CADM4 were not associated with cancer-specific survival or overall survival rate in the cohort of patients in the present study. Whilst these results suggested that CADM1 and CADM4 possess tumor suppressive roles, further functional experiments are required to address the important mechanisms involving CADM1 and CADM4. © 2018, Spandidos Publications. All rights reserved.
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Ikeda, Yuji ; Oda, Katsutoshi ; Hiraike-Wada, Osamu ; Koso, Takahiro ; Miyasaka, Aki ; Kashiyama, Tomoko ; Tanikawa, Michihiro ; Sone, Kenbun ; Nagasaka, Kazunori ; Maeda, Daichi ; Kawana, Kei ; Nakagawa, Shunsuke ; Fukayama, Masashi ; Tetsu, Osamu ; Fujii, Tomoyuki ; Yano, Tetsu ; Kozuma, Shiro ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Cyclin D1 is an important regulator of cell cycle progression. Phosphorylation of cyclin D1 at Thr28
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6 by GSK3β triggers its nuclear export and cytoplasmic proteolysis via the 26S proteasome. Cyclin D1 overexpression is a common event in various types of human cancers; however, reports of mutations are extremely rare. We analyzed mutations of the cyclin D1 gene, CCND1, in 88 endometrial cancer tissue specimens and detected mutations in 2 cases (2.3%). Both were unreported mutations with substitution of threonine to isoleucine at codon 286 (T286I). These two tumors harbored coexisting mutations in K-ras, PIK3CA and/or PTEN and showed accumulation of cyclin D1 in the nucleus by immunohistochemistry. Furthermore, we analyzed the functions of mutant cyclin D1 (T286I) by luciferase assays, immunofluorescence, western blotting and clonogenic cell survival assays in HEK-293T cells. We found that exogenous mutant cyclin D1 (T286I) accumulated in the nuclei in HEK-293T cells, and that it inhibited the expression of pRb. Additionally, the number of colonies was increased by introduction of mutant cyclin D1 (T286I) compared to that of wild-type cyclin D1. In conclusion, we identified an unreported CCND1 mutation (T286I) in two endometrial cancers and revealed that the mutation was functional for inducing cell proliferation in human cells.
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Ohmatsu, Hanako ; Sugaya, Makoto ; Fujita, Hideki ; Miyagaki, Tomomitsu ; Kadono, Takafumi ; Maeda, Daichi ; Takazawa, Yutaka ; Fukayama, Masashi ; Tamaki, Kunihiko ; Sato, Shinichi ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系
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Suzuki, Kensuke ; Nagasaka, Kazunori ; Oda, Katsutoshi ; abe, Hiroyuki ; Maeda, Daichi ; Matsumoto, Yoko ; Arimoto, Takahide ; Kawana, Kei ; Fukayama, Masashi ; Osuga, Yutaka ; Fujii, Tomoyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Background: Lymphangioleiomyomatosis (LAM) is a rare idiopathic disorder that occurs in women of chi
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ldbearing age, and consists of a diffuse proliferation of abnormal smooth muscle cells along the thoracic and abdominal lymphogenous route. Case presentation: We experienced a case of a 47-yo woman with recent history of systemic lupus erythematosus (SLE) diagnosed with endometrial cancer, initially suspected to have metastasized to pelvic and para-aortic lymph nodes based on preoperative diagnostic imaging. Subsequent pathological diagnosis revealed stage IB endometrial cancer without evidence of lymph node involvement. Instead, enlarged pelvic and para-aortic lymph nodes were found to be due to extrapulmonary LAM, from a primary lesion found inside the uterine myometrium. SLE improved after surgery. Conclusion: This is the first reported case of comorbid endometrial cancer, SLE, and aggressive LAM metastasizing to regional lymph nodes, and strengthens the clinical evidence for a common role of mTOR pathway hyperactivity and estrogen responsiveness in the pathophysiology of metastasizing lesions of the genital tract. © 2016 The Author(s).
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Seiki, Takayuki ; Nagasaka, Kazunori ; Kranjec, Christian ; Kawana, Kei ; Maeda, Daichi ; Nakamura, Hiroe ; Taguchi, Ayumi ; Matsumoto, Yoko ; Arimoto, Takahide ; Wada-Hiraike, Osamu ; Oda, Katsutoshi ; Nakagawa, Shunsuke ; Yano, Tetsu ; Fukayama, Masashi ; Banks, Lawrence ; Osuga, Yutaka ; Fujii, Tomoyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Background: The high risk Human Papillomavirus (HPV) E6 oncoproteins play an essential role in the d
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evelopment of cervical malignancy. Important cellular targets of E6 include p53 and the PDZ domain containing substrates such as hScrib and Dlg. We recently showed that hScrib activity was mediated in part through recruitment of protein phosphatase 1γ (PP1γ). Methods: Expression patterns of hScrib and PP1γ were assessed by immunohistochemistry of HPV-16 positive cervical intraepithelial neoplasm (CIN), classified as CIN1 (n=4), CIN2 (n=8), CIN3 (n=8), cervical carcinoma tissues (n=11), and HPV-negative cervical tissues (n=8), as well as by subfractionation assay of the HPV-16 positive cervical cancer cell lines, CaSki and SiHa. To explore the effects of the HPV-16 oncoproteins, we have performed siRNA knockdown of E6/E7 expression, and monitored the effects on the expression patterns of hScrib and PP1γ. Results: We show that PP1γ levels in HPV-16 positive tumour cells are reduced in an E6/E7 dependent manner. Residual PP1γ in these cells is found mostly in the cytoplasm as opposed to the nucleus where it is predominantly found in normal cells. We have found a striking concordance with redistribution in the pattern of expression (9/11; 81.8%) and loss of PP1γ expression in HPV-16 positive cervical tumours (2/11; 18.2%). Furthermore, this loss of PP1γ expression and redistribution in the pattern of expression occurs progressively as the lesions develop (8/8; 100%). Conclusion: Together, these results suggest that PP1γ may be a novel target of the HPV-16 oncoproteins and indicate that it might be a potential novel biomarker for HPV-16 induced malignancy. © Seiki et al.
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| 46.
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Oda, Katsutoshi ; Ikeda, Yuji ; Maeda, Daichi ; Arimoto, Takahide ; Kawana, Kei ; Fukayama, Masashi ; Osuga, Yutaka ; Fujii, Tomoyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Background: Surgical site infections are potential complications following open myomectomy. These in
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fections usually develop immediately after the surgery, and are most often located in the myometrium. Pyogenic cervical cysts are rare and have not been previously reported to occur at the site of myomectomy.Case presentation: A 41-year-old nulligravida Japanese woman was referred to our hospital with a large cervical cyst (>15 cm in diameter). She had undergone a myomectomy 13 years previously, and the surgical site had extended to the endocervical gland. Standard blood tests did not show any evidence of inflammation. The patient underwent a total abdominal hysterectomy, which revealed that the cyst contained multiple components, including Escherichia coli, old blood, and evidence of endometriosis. A pathological review did not show malignant cells within the cyst. The pyogenic cyst originated from the upper anterior cervix, which was one of the sites involved in the previous myomectomy.Conclusion: We reported a huge pyogenic cervical cyst exhibiting signs of endometriosis, in the vicinity of the uterine scar from the open myomectomy. The previous surgery and endometriosis might have contributed to the formation of this rare pyogenic cyst. © 2014 Oda et al.; licensee BioMed Central Ltd.
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| 47.
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Inoue, Tomoko ; Oda, Katsutoshi ; Arimoto, Takahide ; Samejima, Taiki ; Takazawa, Yutaka ; Maeda, Daichi ; Fukayama, Masashi ; Kawana, Kei ; Osuga, Yutaka ; Fujii, Tomoyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Background: Xanthogranulomatous inflammation is an uncommon form of chronic inflammation that is des
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tructive to the normal tissue of affected organs. Although xanthogranulomatous endometritis and xanthogranulomatous salpingitis of the female genital tract has been described previously, to the best of our knowledge, this is the first report of xanthogranulomatous inflammation with infiltration into the uterine myometrium from the perimetrium without endometritis.Case presentation: A 68-year-old Japanese woman with intermittent lower abdominal pain and low-grade fever who was initially treated with antibiotics underwent hysterectomy due to abscess formation in the posterior wall of the myometrium and perimetrium (the outer serosal layer of the uterus). Histopathological findings revealed that the abscess was caused by xanthogranulomatous inflammation with the granulation tissue and chronic inflammatory cells that consisted of focal and sheets of foam cells. The inflammation destroyed the perimetrial elastic lamina, and the myometrium was deeply infiltrated by the xanthoma cells. Neither endometritis nor salpingitis was coexistent with the xanthogranulomatous inflammation.Conclusion: The patient was diagnosed as xanthogranulomatous inflammation, most likely arising from the perimetrium. Our findings suggest that the perimetrium, as well as the endometrium and adnexae, is one of the origins of xanthogranulomatous inflammation in female genital tract. © 2014 Inoue et al.; licensee BioMed Central Ltd.
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| 48.
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Matsumoto, Yoko ; Miyamoto, Yuichiro ; Cabral, Horacio ; Matsumoto, Yu ; Nagasaka, Kazunori ; Nakagawa, Shunsuke ; Yano, Tetsu ; Maeda, Daichi ; Oda, Katsutoshi ; Kawana, Kei ; Nishiyama, Nobuhiro ; Kataoka, Kazunori ; Fujii, Tomoyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Treatment of recurrent or advanced cervical cancer is still limited, and new therapeutic choices are
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needed for improving prognosis and quality of life of patients. Because human papilloma virus (HPV) infection is critical in cervical carcinogenesis, with the E6 and E7 oncogenes of HPV degrading tumor suppressor proteins through the ubiquitin proteasome system, the inhibition of the ubiquitin proteasome system appears to be an ideal target to suppress the growth of cervical tumors. Herein, we focused on the ubiquitin proteasome inhibitor MG132 (carbobenzoxy-Leu-Leu-leucinal) as an anticancer agent against cervical cancer cells, and physically incorporated it into micellar nanomedicines for achieving selective delivery to solid tumors and improving its in vivo efficacy. These MG132-loaded polymeric micelles (MG132/m) showed strong tumor inhibitory in vivo effect against HPV-positive tumors from HeLa and CaSki cells, and even in HPV-negative tumors from C33A cells. Repeated injection of MG132/m showed no significant toxicity to mice under analysis by weight change or histopathology. Moreover, the tumors treated with MG132/m showed higher levels of tumor suppressing proteins, hScrib and p53, as well as apoptotic degree, than tumors treated with free MG132. This enhanced efficacy of MG132/m was attributed to their prolonged circulation in the bloodstream, which allowed their gradual extravasation and penetration within the tumor tissue, as determined by intravital microscopy. These results support the use of MG132 incorporated into polymeric micelles as a safe and effective therapeutic strategy against cervical tumors. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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| 49.
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Nishimura, Riki ; Takita, Junko ; Sato-Otsubo, Aiko ; Kato, Motohiro ; Koh, Katsuyoshi ; Hanada, Ryoji ; Tanaka, Yukichi ; Kato, Keisuke ; Maeda, Daichi ; Fukayama, Masashi ; Sanada, Masashi ; Hayashi, Yasuhide ; Ogawa, Seishi ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Rhabdomyosarcoma (RMS) is a common solid tumor in childhood divided into two histological subtypes,
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embryonal (ERMS) and alveolar (ARMS). The ARMS subtype shows aggressive clinical behavior with poor prognosis, while the ERMS subtype has a more favorable outcome. Because of the rarity, diagnostic diversity and heterogeneity of this tumor, its etiology remains to be completely elucidated. Thus, to identify genetic alterations associated with RMS development, we performed single nucleotide polymorphism array analyses of 55 RMS samples including eight RMS-derived cell lines. The ERMS subtype was characterized by hyperploidy, significantly associated with gains of chromosomes 2, 8 and 12, whereas the majority of ARMS cases exhibited near-diploid copy number profiles. Loss of heterozygosity of 15q was detected in 45.5% of ARMS that had been unrecognized in RMS to date. Novel amplifications were also detected, including IRS2 locus in two fusion-positive tumors, and KRAS or NRAS loci in three ERMS cases. Of note, gain of 13q was significantly associated with good patient outcome in ERMS. We also identified possible application of an ALK inhibitor to RMS, as ALK amplification and frequent expression of ALK were detected in our RMS cohort. These findings enhance our understanding of the genetic mechanisms underlying RMS pathogenesis and support further studies for therapeutic development of RMS. © 2013 Japanese Cancer Association.
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Hiraike, Haruko ; Wada-Hiraike, Osamu ; Nakagawa, Shunsuke ; Saji, Shigehira ; Maeda, Daichi ; Miyamoto, Yuichiro ; Sone, Kenbun ; Tanikawa, Michihiro ; Oda, Katsutoshi ; Nakagawa, Keiichi ; Yano, Tetsu ; Fukayama, Masashi ; Taketani, Yuji ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />DBC1/KIAA1967 (deleted in breast cancer 1) is a putative tumor-suppressor gene cloned from breast ca
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ncer specimens and is reported to regulate p53-dependent apoptosis through its specific inhibition of SIRT1 deacetylase. Although SIRT1 plays a pivotal role in carcinogenesis by regulating cellular proliferation, survival and death, its role in breast cancer remains controversial. Therefore, we aimed to investigate the expression status and clinicopathological significance of DBC1 and SIRT1 in breast cancer tissues. We evaluated the expression of DBC1 and SIRT1 in breast core-needle biopsy specimens from 48 primary breast cancer patients between 2005 and 2008. These patients were treated with primary systemic chemotherapy and subsequent surgical resection of the lesions. Immunohistochemical expression scores of DBC1 and SIRT1 were evaluated, and the relationship between their expression levels and clinicopathological features of breast cancer was analyzed. The expression was observed exclusively in the nuclei of normal and neoplastic ductal cells. In breast biopsy specimens, positive expression of DBC1 and SIRT1 was noted in 85 and 98% of patients, respectively. Expression of DBC1 was significantly associated with the tumor nuclear grade (P=0.019). DBC1 and SIRT1 expression was inversely correlated with HER2 expression (P=0.026 and 0.003, respectively). Lower expression of DBC1 and SIRT1 indicated a tendency for a favorable pathological response to chemotherapy, although this was not statistically significant. Our results reveal that the expression of DBC1 and SIRT1 in breast tissues is associated with tumor characteristics. © 2011 Spandidos Publications Ltd.
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Uni, Masahiro ; Yoshimi, Akihide ; Maki, Hiroaki ; Maeda, Daichi ; Nakazaki, Kumi ; Nakamura, Fumihiko ; Fukayama, Masashi ; Kurokawa, Mineo ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />We report here a 47-year-old male with the diagnosis of high-grade B-cell lymphoma and hemophagocyto
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sis accompanying disseminated intravascular coagulation (DIC). Lymphoma-associated hemophagocytic syndrome (LAHS) is a life-threatening disorder, and LAHS secondary to B-cell lymphoma is relatively rare compared to that secondary to T- or NK/T-cell lymphoma in Western countries. T- or NK/T-cell LAHS is sometimes combined with DIC, which makes patients' outcomes even worse, but few reports of B-cell LAHS accompanying DIC has been published so far. We successfully treated a patient with this condition with recombinant thrombomodulin (rTM), a novel agent for DIC. We believe that rTM is a therapeutic option in cases with B-cell LAHS accompanying DIC.
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| 52.
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Maeda, Daichi ; Tsui-Lien, Mao ; Fukayama, Masashi ; Nakagawa, Shunsuke ; Yano, Tetsu ; Taketani, Yuji ; Shih, Ie-Ming ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Recent genome-wide analysis has demonstrated that somatic mutations in ARID1A (BAF250) are the most
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common molecular genetic changes in ovarian clear cell carcinoma (OCCC). ARID1A mutations, which occur in approximately half of OCCC cases, lead to deletion of the encoded protein and inactivation of the putative tumor suppressor. In this study, we determined the significance of loss of ARID1A immunoreactivity with respect to several clinicopathological features in a total of 149 OCCCs. First, we demonstrated that ARID1A immunohistochemistry showed concordance with the mutational status in 91% of cases with 100% sensitivity and 66% specificity. Specifically, among 12 OCCC cases for which ARIDA mutational status was known, ARIDIA immunoreactivity was undetectable in all 9 cases harboring ARID1A mutations and was undetectable in one of 3 cases with wild-type ARID1A. With respect to the entire cohort, ARID1A immunoreactivity was undetectable in 88 (59%) of 149 OCCCs. There was no significant difference between ARID1A negative and positive cases in terms of histopathologic features, age, clinical stage, or overall survival. In conclusion, this study provides further evidence that mutations in ARID1A resulted in loss of ARID1A protein expression in OCCC, although no significant differences between ARID1A positive and negative cases were observed with respect to any clinicopathological features examined. © 2010 by the authors.
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| 53.
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Shiraishi, Kouya ; Okada, Yukinori ; Takahashi, Atsushi ; Kamatani, Yoichiro ; Momozawa, Yukihide ; Ashikawa, Kyota ; Kunitoh, Hideo ; Matsumoto, Shingo ; Takano, Atsushi ; Shimizu, Kimihiro ; Goto, Akiteru ; Tsuta, Koji ; Watanabe, Shun-ichi ; Ohe, Yuichiro ; Watanabe, Yukio ; Goto, Yasushi ; Nokihara, Hiroshi ; Furuta, Koh ; Yoshida, Akihiko ; Goto, Koichi ; Hishida, Tomoyuki ; Tsuboi, Masahiro ; Tsuchihara, Katsuya ; Miyagi, Yohei ; Tanaka, Kazumi ; Nakayama, Haruhiko ; Yokose, Tomoyuki ; Nagashima, Toshiteru ; Ohtaki, Yoichi ; Maeda, Daichi ; Imai, Kazuhiro ; Minamiya, Yoshihiro ; Sakamoto, Hiromi ; Saito, Akira ; Shimada, Yoko ; Sunami, Kuniko ; Saito, Motonobu ; Inazawa, Johji ; Nakamura, Yusuke ; Yoshida, Teruhiko ; Yokota, Jun ; Matsuda, Fumihiko ; Matsuo, Keitaro ; Daigo, Yataro ; Kubo, Michiaki ; Kohno, Takashi ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than
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in European/Americans (10-20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10 '17, per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10 '9, per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations.
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| 54.
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Oki, Shinya ; Sone, Kenbun ; Oda, Katsutoshi ; Hamamoto, Ryuji ; Ikemura, Masako ; Maeda, Daichi ; Takeuchi, Makoto ; Tanikawa, Michihiro ; Mori-Uchino, Mayuyo ; Nagasaka, Kazunori ; Miyasaka, Aki ; Kashiyama, Tomoko ; Ikeda, Yuji ; Arimoto, Takahide ; Kuramoto, Hiroyuki ; Wada-Hiraike, Osamu ; Kawana, Kei ; Fukayama, Masashi ; Osuga, Yutaka ; Fujii, Tomoyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />The histone methyltransferase EZH2, a key epigenetic modifier, is known to be associated with human
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tumorigenesis. However, the physiological importance of EZH2 and its clinical relevance in endometrial cancer remain unclear. Hence, in the present study, we investigated the expression and function of EZH2 in endometrial cancer. In a quantitative real-time PCR analysis of 11 endometrial cancer cell lines and 52 clinical endometrial cancer specimens, EZH2 was significantly overexpressed in cancer cells and tissues compared to that in corresponding normal control cells and tissues. Kaplan-Meier survival analysis using data of the TCGA RNA-seq database and tissue microarrays (TMAs) indicated that EZH2 overexpression is associated with endometrial cancer prognosis. In addition, knockdown of EZH2 using specific siRNAs resulted in growth suppression and apoptosis induction of endometrial cancer cells, accompanied by attenuation of H3K27 trimethylation. Consistent with these results, treatment with GSK126, a specific EZH2 inhibitor, suppressed endometrial cancer cell growth and decreased the number of cancer cell colonies. Furthermore, GSK126 showed additive effects with doxorubicin or cisplatin, which are conventional drugs for treatment of endometrial cancer. Further studies should explore the therapeutic potential of inhibiting EZH2 in patients with endometrial cancer. © Oki et al.
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| 55.
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Goto, Akiteru ; Masamitsu, Tanaka ; Yoshida, Makoto ; Umakoshi, Michinobu ; Nanjo, Hiroshi ; Shiraishi, Kouya ; Saito, Motonobu ; Kohno, Takashi ; Kuriyama, Sei ; Konno, Hayato ; Imai, Kazuhiro ; Hajime, Saito ; Minamiya, Yoshihiro ; Maeda, Daichi ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Purpose miR-451 is a tumor suppressive microRNA with several target genes, including Macrophage migr
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ation inhibitory factor (MIF). As little is known about the expression and clinicopathological significance of mir-451 in NSCLC, we performed a clinicopathological study of 370 NSCLC cases to clarify them. Cell biological experiments were also performed on NSCLC cell lines to confirm the tumor-suppressive role of miR-451 and whether or not MIF is targeted by miR-451. Methods We analyzed 370 NSCLC cases for the miR-451 expression by quantitative real-time polymerase chain reaction and the MIF expression by immunohistochemistry. Eighty-four background lung tissue samples were also evaluated for the miR-451 expression. The clinicopathological and genetic factors surveyed were the disease-free survival, smoking status, histological type, disease stage, EGFR gene mutations and ALK rearrangements. In 286 adenocarcinoma cases, the invasive status (adenocarcinoma in situ, minimally invasive adenocarcinoma and invasive adenocarcinoma) was also evaluated. Five NSCLC cell lines (H23, H441, H522, H1703, and H1975) were cultured and evaluated for their miR-451 and MIF expression. The cell lines with lower miR-451 and higher MIF expressions were then selected and transfected with miR-451-mimic to observe its effects on MIF expression, Akt and Erk status, cell proliferation, and cell migration. Results The miR-451 expression was down-regulated in cancer tissues compared with background lung tissues (P<0.0001). Factors such as advanced disease stage, positive pleural invasion and nodal status and being a smoker were significantly correlated with a lower expression of miR-451 (P<0.05 each), while EGFR gene mutations and ALK rearrangements were not. In adenocarcinoma, invasive and minimally invasive adenocarcinoma showed lower expression of miR-451 than adenocarcinoma in situ (P<0.0005, respectively). A survival analysis showed that a lower expression of miR-451 was an independent predictor of a poor prognosis for NSCLC (P<0.05). The MIF expression was inversely correlated with the miR-451 expression. Out of 5 NSCLC cell lines examined, H441 and H1975 showed higher MIF and lower miR-451 expressions. After the transfection of miR-451-mimic, the MIF expression and phosphorylated Akt expression of these cell lines was suppressed, as were cell proliferation and cell migration. Conclusion This clinicopathological study of 370 NSCLC cases and the cell biological studies of NSCLC cell lines clarified the tumor-suppressive role of miR-451 and its prognostic value. We also validated MIF as a target of miR-451 in NSCLC. © 2017 Goto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Kito, Masahiko ; Maeda, Daichi ; Kudo-Asabe, Yukitsugu ; Sato, Naoki ; Ie-Ming, Shih ; Wang, Tian-Li ; Tanaka, Masamitsu ; Terada, Yukihiro ; Goto, Akiteru ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />In Table 1, the values in the Case column should be listed from 1 to 18. Please see the corrected Ta
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ble 1 here. © 2016 Kito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br />Correction to: PLoS ONE https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156069
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Kito, Masahiko ; Maeda, Daichi ; Kudo-Asabe, Yukitsugu ; Sato, Naoki ; Ie-Ming, Shih ; Wang, Tian-Li ; Tanaka, Masamitsu ; Terada, Yukihiro ; Goto, Akiteru ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />There is a growing body of evidence regarding cell competition between normal and mutant mammalian c
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ells, which suggest that it may play a defensive role in the early phase of carcinogenesis. In vitro study in the past has shown that overexpression of vimentin in normal epithelial cells at the contact surface with transformed cells is essential for the cell competition involved in epithelial defense against cancer. In this study, we attempted to examine cell competition in human tissue in vivo by investigating surgically resected human fallopian tubes that contain p53 signatures and serous tubal intraepithelial lesions (STILs), a linear expansion of p53-immunopositive/TP53 mutant tubal epithelial cells that are considered as precursors of pelvic high grade serous carcinoma. Immunofluorescence double staining for p53 and the cell competition marker vimentin was performed in 21 sections of human fallopian tube tissue containing 17 p53 signatures and 4 STILs. The intensities of vimentin expression at the interface between p53-positive cells at the end of the p53 signature/STIL and adjacent p53-negative normal tubal epithelial cells were compared with the background tubal epithelium. As a result, the average vimentin intensity at the interfaces relative to the background intensity was 1.076 (95% CI, 0.9412-1.211 for p53 signature and 0.9790 (95% CI, 0.7206-1.237) for STIL. Thus, it can be concluded that overexpression of the cell competition marker vimentin are not observed in human tissue with TP53 alterations. © 2016 Kito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Maeda, Daichi ; Yoshiyuki, Akiyama ; Morikawa, Teppei ; Kunita, Akiko ; Ota, Yasunori ; Katoh, Hiroto ; Niimi, Aya ; Nomiya, Akira ; Ishikawa, Shumpei ; Goto, Akiteru ; Igawa, Yasuhiko ; Fukayama, Masashi ; Homma, Yukio ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Interstitial cystitis (IC) is a chronic bladder disease with urinary frequency, bladder discomfort o
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r bladder pain of unknown etiology. Based on cystoscopic findings, patients with IC are classified as either Hunner-type/classic IC (HIC), presenting with a specific Hunner lesion, or non-Hunner-type IC (NHIC), presenting with no Hunner lesion, but post-hydrodistension mucosal bleeding. Inflammatory cell infiltration, composed predominantly of lymphocytes, plasma cells and epithelial denudation, has in the past been documented as a major pathological IC finding. However, the significance of the pathological evaluation of IC, especially with regard to the difference between HIC and NHIC, has been downplayed in recent years. In this study, we performed immunohistochemical quantification of infiltrating T-lymphocytes, B-lymphocytes and plasma cells, and measured the amount of residual epithelium in urinary bladder biopsy specimens taken from patients with HIC and NHIC, and those with no IC, using image analysis software. In addition, in situ hybridization of the light chains was performed to examine clonal B-cell expansion. Lymphoplasmacytic infiltration was significantly more severe in HIC specimens than in NHIC specimens (P <0.0001). Substantial lymphoplasmacytic inflammation (≥200 cells/mm2) was observed in 93% of HIC specimens, whereas only 8% of NHIC specimens were inflamed. Plasmacytic infiltration was more prominent in HIC specimens compared with NHIC and non-IC cystitis specimens (P <0.005). Furthermore, expansion of light-chain-restricted B-cells was observed in 31% of cases of HIC. The amount of residual epithelium was decreased in HIC specimens compared with NHIC specimens and non-IC cystitis specimens (P <0.0001). These results suggest that NHIC and HIC are distinct pathological entities, with the latter characterized by pancystitis, frequent clonal B-cell expansion and epithelial denudation. An abnormality in the B-cell population may be involved in the pathogenesis of HIC. © 2015 Maeda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Uehara, Yuriko ; Oda, Katsutoshi ; Ikeda, Yuji ; Koso, Takahiro ; Tsuji, Shingo ; Yamamoto, Shogo ; Asada, Kayo ; Sone, Kenbun ; Kurikawa, Reiko ; Makii, Chinami ; Hagiwara, Otoe ; Tanikawa, Michihiro ; Maeda, Daichi ; Hasegawa, Kosei ; Nakagawa, Shunsuke ; Wada-Hiraike, Osamu ; Kawana, Kei ; Fukayama, Masashi ; Fujiwara, Keiichi ; Yano, Tetsu ; Osuga, Yutaka ; Fujii, Tomoyuki ; Aburatani, Hiroyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Correction to: PLoS ONE https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128066
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Uehara, Yuriko ; Oda, Katsutoshi ; Ikeda, Yuji ; Koso, Takahiro ; Tsuji, Shingo ; Yamamoto, Shogo ; Asada, Kayo ; Sone, Kenbun ; Kurikawa, Reiko ; Makii, Chinami ; Hagiwara, Otoe ; Tanikawa, Michihiro ; Maeda, Daichi ; Hasegawa, Kosei ; Nakagawa, Shunsuke ; Wada-Hiraike, Osamu ; Kawana, Kei ; Fukayama, Masashi ; Fujiwara, Keiichi ; Yano, Tetsu ; Osuga, Yutaka ; Fujii, Tomoyuki ; Aburatani, Hiroyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Ovarian clear cell carcinoma (CCC) is generally associated with chemoresistance and poor clinical ou
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tcome, even with early diagnosis; whereas high-grade serous carcinomas (SCs) and endometrioid carcinomas (ECs) are commonly chemosensitive at advanced stages. Although an integrated genomic analysis of SC has been performed, conclusive views on copy number and expression profiles for CCC are still limited. In this study, we performed single nucleotide polymorphism analysis with 57 epithelial ovarian cancers (31 CCCs, 14 SCs, and 12 ECs) and microarray expression analysis with 55 cancers (25 CCCs, 16 SCs, and 14 ECs). We then evaluated PIK3CA mutations and ARID1A expression in CCCs. SNP array analysis classified 13% of CCCs into a cluster with high frequency and focal range of copy number alterations (CNAs), significantly lower than for SCs (93%, P < 0.01) and ECs (50%, P = 0.017). The ratio of whole-arm to all CNAs was higher in CCCs (46.9%) than SCs (21.7%; P < 0.0001). SCs with loss of heterozygosity (LOH) of BRCA1 (85%) also had LOH of NF1 and TP53, and LOH of BRCA2 (62%) coexisted with LOH of RB1 and TP53. Microarray analysis classified CCCs into three clusters. One cluster (CCC-2, n = 10) showed more favorable prognosis than the CCC-1 and CCC-3 clusters (P = 0.041). Coexistent alterations of PIK3CA and ARID1A were more common in CCC-1 and CCC-3 (7/11, 64%) than in CCC-2 (0/10, 0%; P < 0.01). Being in cluster CCC-2 was an independent favorable prognostic factor in CCC. In conclusion, CCC was characterized by a high ratio of whole-arm CNAs; whereas CNAs in SC were mainly focal, but preferentially caused LOH of well-known tumor suppressor genes. As such, expression profiles might be useful for sub-classification of CCC, and might provide useful information on prognosis. © 2015 Uehara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Ito, Yukinobu ; Yoshida, Makoto ; Maeda, Daichi ; Takahashi, Masato ; Nanjo, Hiroshi ; Masuda, Hirotake ; Gopto, Akiteru ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Arteriovenous malformations consist of tangles of arteries and veins that are often connected by a f
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istula. The causes and mechanisms of these clinical entities are not fully understood. We discovered that suturing an arterial patch into the common jugular vein of rabbits led to spontaneous neovascularization, the formation of an arteriovenous fistula and the development of an arteriovenous shunt. An arterial patch excised from the common carotid artery was sutured into the common jugular vein. Within a month, a dense nidus-like neovasculature formed around the patch. Angiography and pulse-oximeter analyses showed that the blood flowing into the neovasculature was arterial blood. This indicated that an arteriovenous shunt had formed. Fluorescence in situ hybridization with a Y chromosome probe in female rabbits that received an arterial patch from male rabbits showed that the vessels close to the graft bore the Y chromosome, whereas the vessels further away did not. Enzyme-linked immunosorbent assays and cDNA microarray analysis showed that multiple angiogenic factors were upregulated after patch transplantation. This is the first in vivo model of spontaneous arteriovenous fistula formation. Further research on these differences may help to improve understanding of human vascular anomaly diseases and the basic principles underlying vasculogenesis and/or angiogenesis. © 2018 The Author(s).
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| 62.
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Takahashi, Kenichi ; Mashima, Hirosato ; Miura, Kouichi ; Maeda, Daichi ; Goto, Akiteru ; Gotio, Takashi ; Sun-Wada, Ge-Hong ; Wada, Yoh ; Ohnishi, Hirohide ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Although aberrations of intracellular vesicle transport systems towards lysosomes including autophag
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y and endocytosis are involved in the onset and progression of acute pancreatitis, the molecular mechanisms underlying such aberrations remain unclear. The pathways of autophagy and endocytosis are closely related, and Rab7 plays crucial roles in both. In this study, we analyzed the function of Rab7 in acute pancreatitis using pancreas-specific Rab7 knockout (Rab7Δpan) mice. In Rab7Δpan pancreatic acinar cells, the maturation steps of both endosomes and autophagosomes were deteriorated, and the lysosomal functions were affected. In experimental models of acute pancreatitis, the histopathological severity, serum amylase concentration and intra-pancreatic trypsin activity were significantly higher in Rab7Δpan mice than in wild-type mice. Furthermore, the autophagy process was blocked in Rab7Δpan pancreas compared with wild-type mice. In addition, larger autophagic vacuoles that colocalize with early endosome antigen 1 (EEA1) but not with lysosomal-associated membrane protein (LAMP)-1 were much more frequently formed in Rab7Δpan pancreatic acinar cells. Accordingly, Rab7 deficiency exacerbates the severity of acute pancreatitis by impairing the autophagic and endocytic pathways toward lysosomes.
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| 63.
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Akiyama, Yoshiyuki ; Morikawa, Teppei ; Maeda, Daichi ; Shintani, Yukako ; Niimi, Aya ; Nomiya, Akira ; Nakayama, Atsuhito ; Igawa, Yasuhiko ; Fukayama, Masashi ; Homma, Yukio ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />An up-regulated CXCR3 pathway and affluent plasma cell infiltration are characteristic features of H
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unner type interstitial cystitis (HIC). We further examined these two features using bladder biopsy samples taken from 27 patients with HIC and 15 patients with non-IC cystitis as a control. The number of CD3-positive T lymphocytes, CD20-positive B lymphocytes, CD138-positive plasma cells, and CXCR3-positive cells was quantified by digital image analysis. Double-immunofluorescence for CXCR3 and CD138 was used to detect CXCR3 expression in plasma cells. Correlations between CXCR3 positivity and lymphocytic and plasma cell numbers and clinical parameters were explored. The density of CXCR3-positive cells showed no significant differences between HIC and non-IC cystitis specimens. However, distribution of CXCR3-positivity in plasma cells indicated co-localization of CXCR3 with CD138 in HIC specimens, but not in non-IC cystitis specimens. The number of CXCR3-positive cells correlated with plasma cells in HIC specimens alone. Infiltration of CXCR3-positive cells was unrelated to clinical parameters of patients with HIC. These results suggest that infiltration of CXCR3-positive plasma cells is a characteristic feature of HIC. The CXCR3 pathway and specific immune responses may be involved in accumulation/retention of plasma cells and pathophysiology of the HIC bladder.
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| 64.
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津田, 武明 ; Tsuda, Takeaki
概要:
金沢大学先端科学・社会共創推進機構<br />The characteristics of four roll coating system were numerically investigated compared with exper
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imental data to validate theoretical models used in this research. In the theoretical models, a film splitting model using a power-law type equation, a roll gap model based on elasto-hydrodynamics and a flow model from a rotating cylinder system were applied. The parametric computations to each operation condition revealed the steady and dynamic behaviors of a coating film and liquid films on coating rolls. From the results of the frequency response to the speed disturbances of the coating rolls, it was found that the sensitivity of the lowest coating roll to the disturbance was a half of others, which implies that the requirement for the accuracy of a driving system for the coating roll is not so severe compared with others. The experimental data and the numerical results at steady state agreed in large part. The actual properties of materials used in the coating process will be required to predict the coating thickness precisely. © 2011 The Japan Society of Mechanical Engineers.
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| 65.
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衣川, 洋史 ; 津田, 武明 ; 中野, 公一 ; 京藤, 敏達 ; Kinugawa, Hiroshi ; Tsuda, Takeaki ; Nakano, Koichi ; Kyoto, Harumichi
概要:
金沢大学先端科学・社会共創推進機構<br />The Hybrid 1D/2D flow model for non-Newtonian fluids in a single cavity die with a slit is presen
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ted. The equations of mass and momentum in a cavity are treated one-dimensionally by assuming an appropriate mean flow over the cross section of the flow. The governing equations inside the slot are treated two-dimensionally by the lubrication theory and assuming an appropriate mean flow. The equations of flow for the cavity and the slot are derived and then coupled. We use a finite element method to solve these governing equations. It is concluded that slot's geometry, fluid properties and machining accuracy affect the uniformity of the flow from the slot. © 2012 The Japan Society of Mechanical Engineers.
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| 66.
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津田, 武明 ; 須藤, 通孝 ; 水野, 春奈 ; 伊藤, 真樹 ; Tsuda, Takeaki ; Suto, Michitaka ; Mizuno, Haruna ; Itoh, Maki
概要:
金沢大学先端科学・社会共創推進機構<br />Original experimental and computational models for PSAs for flexible displays have been studied t
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o clarify the property target for the PSA development. Possible defects in the devices, crack formation, delamination, and residual strain were addressed by a new theory, "Multiple-Neutral-Plane Phenomena", with an originally developed software using Vector Finite Element Method. Peel adhesion values were found to be correlated with tan δ from DMA multiplied by tensile modulus from stress-strain curves, which offered a prediction equation for peel strength. The study has enabled a PSA material producer to develop PSAs for the application. © 2019 Society of Rheology.
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| 67.
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穴澤, 朝彦 ; 津田, 武明 ; 吉羽, 洋 ; 鳴海, 敬倫 ; 藤澤, 延行 ; 山縣, 貴幸 ; 長谷川, 富市 ; Anazawa, Tomohiko ; Tsuda, Takeaki ; Yoshiba, Hiroshi ; Narumi, Takatune ; Fujisawa, Nobuyuki ; Yamagata, Takayuki ; Hasegawa, Tomiichi
概要:
金沢大学先端科学・社会共創推進機構<br />In this work, entrance flows of viscoelastic fluids from a cavity to a slot in a slot die coating
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were investigated experimentally and numerically. Aqueous solutions of polyethylene glycol (PEG) and polyethylene oxide (PEO) mixtures, having viscoelasticity and Newtonian viscosity, were tested in order to clarify the effects of viscoelastic characteristics to the excess pressure drops at the entrance. The measured excess pressure drop changes corresponded to the flow pattern changes from a Newtonian-like flow pattern to vortex generation and growth patterns in an asymmetric entrance flow with a submillimeter slot. Numerical predictions of the transitions in the flow patterns and the pressure drops were also made utilizing exponential Phan-Thien-Tanner (EPTT) model with a finite element method. The predictions qualitatively indicated the increase in excess pressure drop and the vortex generation and growth. © 2012 The Society of Rheology, Japan.
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| 68.
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津田, 武明 ; 長島, 正幸 ; 穴澤, 朝彦 ; 長谷川, 富市 ; Tsuda, Takeaki ; Nagashima, Masayuki ; Anazawa, Tomohiko ; Hasegawa, Tomiichi
概要:
金沢大学先端科学・社会共創推進機構<br />In this study, the fast numerical computation method by using simplified momentum equations, whic
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h exactly clarified the flow state inside a slot die, was developed, in order to obtain higher coating quality. The computation results elucidated the dependence of the uniformity of coating thickness on non-Newtonian characteristics. In addition, it was found that the computational procedure enables us to seek the optimum internal figures of a slot die immediately. The method was extended to a variety of rheological models, such as Power-Law, Ellis and Hershel-Bulkley model. As a result, the computation technique industrially contributed to the development of precise coating productions, such as optical elements, semiconductor and LCD display components. © 2011 The Society of Rheology, Japan.
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| 69.
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Tsuda, Takeaki ; 津田, 武明
概要:
金沢大学先端科学・社会共創推進機構<br />One-dimensional flow equations were derived for non-Newtonian fluids in slot coating and a simple
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numerical method was proposed to solve the equations. We investigated non-Newtonian effects on coating performance and coating quality in slot coating. In some cases, computational results and experimental data were compared and both agreed well. A series of numerical computations showed that the one-dimensional approach can describe non-Newtonian flow under lips in a few minutes and that a pressure field equation proposed by Higgins can determine the location of an upstream meniscus. Moreover, it was found that the non-Newtonian characteristics of coating liquids affect both coating performance and coating quality. Because each non-Newtonian effect is quite different, we should optimize the conditions of slot coating and die geometries according to the target problem. © 2010 The Society of Rheology, Japan.
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| 70.
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穴澤, 朝彦 ; 津田, 武明 ; 吉羽, 洋 ; 鳴海, 敬倫 ; 長谷川, 富市 ; Anazawa, Tomohiko ; Tsuda, Takeaki ; Yoshiba, Hiroshi ; Narumi, Takatsune ; Hasegawa, Tomiichi
概要:
金沢大学先端科学・社会共創推進機構<br />Flows of a viscoelastic fluid in slot die coating were experimentally and theoretically investiga
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ted. A viscoelastic fluid having a constant viscosity and a relaxation time (Boger fluid) as well as Newtonian fluid were used as test liquids in a wide range of Weissenberg numbers (0 < Wi < 42). We observed experimentally that the Boger fluid reduced the widthwise non-uniformity of the flow inside a slot die as flow rates were increased. However, this advantage disappeared in the higher flow rate region. This was not observed in the case of Newtonian fluids. In order to depict this behavior, a one-dimensional flow model was presented, where cavity flow and slot flow were combined by means of a planar entrance flow. The pressure drop induced by the planar entrance flow was assumed to characterize the flow from a cavity to a slot. Moreover, an excess pressure drop due to the viscoelasticity was empirically estimated, where the high deformation rates attained in the entrance flow from the cavity to the slot caused the increase of the excess pressure drop. The prediction by this model qualitatively agreed with the experimental results and showed utility of the proposed simple model. © 2009 The Society of Rheology, Japan.
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| 71.
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中野, 公一 ; 山本, 和秀 ; 津田, 武明 ; 京藤, 敏達 ; Nakano, Koichi ; Yamamoto, Kazuhide ; Tsuda, Takeaki ; Kyotoh, Harumichi
概要:
金沢大学先端科学・社会共創推進機構<br />Prediction of particle concentration distribution from a slot die is presented. The uniformity of
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particle concentration distribution is predicted by the particle trajectory in a slot die. In order to depict the movement of particles in the slot die, we coupled the one-dimensional flow equations in a slot die and Stokesian sedimentation equation. It is concluded that Reynolds number and particle diameters affect the uniformity of the particle concentration from the slit, and the predictions using the presented model agree with the experimental results.
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| 72.
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中野, 公一 ; 津田, 武明 ; 京藤, 敏達 ; Nakano, Koichi ; Tsuda, Takeaki ; Kyotoh, Harumichi
概要:
金沢大学先端科学・社会共創推進機構<br />In this study, the uniformity of particle concentration in a cavity die containing the unstable d
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ispersed particles is predicted by using one-dimensional flow model for non-Newtonian fluid in a cavity and the Stokesian sedimentation model. In order to depict the movement of particles, the equation combining the one-dimensional flow equation in a cavity with the particle concentration equation predicting the sedimentation is derived. We investigated the resolution to avoid the sedimentation from the operational and material point of views. As a result, we found the appropriate conditions to prevent from the problems.
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| 73.
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神保, 洋貴 ; 京藤, 敏達 ; 中野, 公一 ; 津田, 武明 ; 株式会社IHI ; 筑波大学大学院システム情報系 ; Jinbo, Hiroki ; Kyotoh, Harumichi ; Nakano, Koichi ; Tsuda, Takeaki ; Graduate, School of Systems and Information University of Tsukuba ; Dai Nippon Printing Co. Ltd.
概要:
金沢大学先端科学・社会共創推進機構
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| 74.
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相澤, 栄次 ; 津田, 武明 ; 阪野, 伸大 ; 今駒, 博信 ; 大村, 直人 ; Aizawa, Eiji ; Tsuda, Takeaki ; Sakano, Nobuhiro ; Imakoma, Hironobu ; Ohmura, Naoto
概要:
金沢大学先端科学・社会共創推進機構<br />Particle dispersion in a stirred vessel with dual paddle impellers was numerically investigated b
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y a commercial CFD code. The working fluid was assumed a weak shear-thinning non-Newtonian fluid or Newtonian fluid having low viscosity (ca. 4.0 Pa · s). Particles were initially set in the lower half region in the vessel. Numerical simulations were conducted by varying rheological property, location of the impellers and discharge flow rate of impellers. Numerical results showed that the viscosity was lower near the impeller in the non-Newtonian fluid than in the Newtonian fluid due to strong shear near the forefront of impeller. Consequently, the velocity of discharge flow from impeller was larger in the non-Newtonian. Larger velocity of the discharge flow took more particles to the tank wall as compared with Newtonian fluid. The present work adopted the mean value and the standard deviation of particle concentration as particle dispersion indexes. It has been found that the standard deviation depends on particle dispersion process.
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| 75.
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篠田, 隆行 ; Shinoda, Takayuki
概要:
金沢大学先端科学・社会共創推進機構
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| 76.
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篠田, 隆行 ; Shinoda, Takayuki
概要:
金沢大学先端科学・社会共創推進機構
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| 77.
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表, 真美 ; 小倉, 育代 ; 大本, 久美子 ; 岸本, 幸臣 ; 長石, 啓子 ; 花輪, 由樹 ; 宮崎, 陽子 ; 吉井, 美奈子 ; Omote, Mami ; Ogura, Ikuyo ; Ohmoto, Kumiko ; Kishimoto, Yukiomi ; Nagaishi, Keiko ; Hanawa, Yuki ; Miyazaki, Yoko ; Yoshii, Minako
概要:
金沢大学人間社会研究域学校教育系
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| 78.
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花輪, 由樹 ; 小倉, 育代 ; 大本, 久美子 ; 表, 真美 ; 岸本, 幸臣 ; 長石, 啓子 ; 宮崎, 陽子 ; 吉井, 美奈子 ; Hanawa, Yuki ; Ogura, Ikuyo ; Ohmoto, Kumiko ; Omote , Mami ; Kishimoto, Yukiomi ; Nagaishi, Keiko ; Miyazaki, Yoko ; Yoshii, Minako
概要:
金沢大学人間社会研究域学校教育系
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| 79.
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表, 真美 ; 土井, ギーゼラ ; 花輪, 由樹 ; 小倉, 育代 ; Omote , Mami ; Doi, Gisela ; Hanawa, Yuki ; Ogura, Ikuyo
概要:
金沢大学人間社会研究域学校教育系<br />The purpose of this study is to clarify the Home Economics education situation in primary and seco
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ndary schools in Hessen, Germany. The study is based on research of the standard curriculum and textbooks in use, as well as interviews with teachers, pupils and graduates while visiting a school in Hessen, Germany in September 2014. The results were as follows: 1. In the curriculum of the Hessen primary and lower secondary school that we visited, Home Economics and sewing education have not been positioned as compulsory subjects. 2. One of the content items in “art” at primary school is “sewing education”. Textbooks are not used in art classes. The art classes vary, depending on schools and teachers. 3. Food education is included in “body”, which is one of the learning content items of the comprehensive subject “Sachunterricht”. The “Sachunterricht” textbooks contain the contents of food education. Nutritional, food, and cooking education are practiced in the primary school we visited.
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| 80.
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花輪, 由樹 ; Hanawa, Yuki
概要:
金沢大学人間社会研究域学校教育系<br />This paper attempts to elucidate the coexistence of “the remaining ‘Heimat’ for children” and “‘He
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imat’ defined by their ancestors and others” in the field of dwelling education by focusing on ideas on the term in E. Spranger's works. Spranger says that ‘Heimat’is characterized and linked to the soil where people live and experience on a daily basis. In short, it became clear that through the teacher's advice “third-person-defined ‘Heimat’” can exist next to the definition of ‘Heimat’children themselves have in their minds.
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| 81.
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花輪, 由樹 ; 西垣, 安比古 ; Hanawa, Yuki ; Nishigaki, Yasuhiko
概要:
金沢大学人間社会研究域学校教育系<br />This paper attempts to elucidate about a transition on volume changes of “home province” and “regi
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on” in course of study and a meaning of remaining “home province” in the showa 40s that was times changed from “home province” to “region”. First, in elementary school and junior high school, it was only in “social studies” that changed from “home province” to “region”. Secondly, for education about sense of dwelling, “home province” in the showa 40s was not sufficient.
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| 82.
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花輪, 由樹 ; 大本, 久美子 ; Hanawa, Yuki ; Ohmoto, Kumiko
概要:
金沢大学人間社会研究域学校教育系<br />本稿は,大学生の食行動に関する質問紙調査と高等学校の家庭科教科書の分析により,消費者市民育成のあり方を探ったものである。質問紙調査では,大学生は食を選ぶ際に,安くて量のあるものを重視し,産地や添加
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物などの安全面はあまり気にしていないことが明らかになった。そして教科書分析によれば,食領域では「自分のための食」「地球のための食」についての記載は多いものの,「地域の食」についての内容が稀薄であった。今後家庭科で消費者市民意識を育むためには,「自分・家族・地域・国・地球」という幅広い視点から,生活行為の選択ができるような教科書の充実が望まれることを考察した。<br />This paper aims to clarify how to encourage consumer citizenship of dietary field in home economics education by means of by two surveys. The first survey is a questionnaire about university students' dietary behavior. It was carried out in a teacher's college. It became clear that university students focus on cheapness and quantity of food. On the other hand they do not pay much attention to security aspects such as the food additives and production source when they select their meal. The second survey analyzes home economics textbooks of home economics in high school. The analysis demonstrates that there are more articles about `food for themselves' and `food for earth' rather than `food for region' in the text books on the dietary field. Therefore it seems necessary to change contents of the text books from a wider perspective view such as `food for themselves, family, region, Japan and earth' in order to foster consumer citizenship in home economics.<br />出版者の許可を得て登録_20210726
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| 83.
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Asano, Tetsuo ; Mulzer, Wolfgang ; Wang, Yajun ; 浅野, 哲夫
概要:
金沢大学<br />Constant-work-space algorithms model computation when space is at a premium: the input is given as a read-only
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array that allows random ac- cess to its entries, and the algorithm may use constantly many additional registers of O(logn) bits each, where n denotes the input size. We present such algorithms for two restricted variants of the shortest path problem. First, we describe how to report a simple path between two arbitrary nodes in a given tree. Using a technique called "computing instead of storing", we obtain a naive algorithm that needs quadratic time and a constant number of additional registers. We then show how to improve the running time to linear by applying a technique named "simulated parallelization". Second, we show how to compute a shortest geodesic path between two points in a simple polygon in quadratic time and with constant work-space.
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| 84.
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Asano, Tetsuo ; Demaine, Erik D. ; Demaine, Martin L. ; Uehara, Ryuhei ; 浅野, 哲夫
概要:
金沢大学<br />Kaboozle is a puzzle consisting of several square cards, each annotated with colored paths and dots drawn on b
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oth sides and holes drilled. The goal is to join two colored dots with paths of the same color (and fill all holes) by stacking the cards suitably. The freedoms here are to reflect, rotate, and order the cards arbitrarily, so it is not surprising that the problem is NP-complete (as we show). More surprising is that any one of these freedoms-reflection, rotation, and order-is alone enough to make the puzzle NP-complete. Furthermore, we show NP-completenessof a particularly constrained form of Kaboozle related to 1D paper folding. Specifically, we suppose that the cards are glued together into a strip, where each glued edge has a specified folding direction (mountain or valley). This variation removes the ability to rotate and reflect cards, and restricts the order to be a valid folded state of a given 1D mountain-valley pattern. © 2012 Information Processing Society of Japan.
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| 85.
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論文
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Higuchi, Akihiro ; 樋口, 明弘
概要:
金沢大学先端科学・社会共創推進機構<br />Dry eye syndrome is a multifactorial condition on the tear and ocular surface. Autologous serum e
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ye drop is an effective method for treating dry eye. Autologous serum eye drops are now widely used by specialists since a first report in 1975. The results of a systematic study showed that the efficacy of autologous serum eye drops remains ambiguous because its preparation methods and clinical application have not been standardized. To elucidate the efficacy of autologous serum eye drops, well-designed, large-scale, high-quality randomized controlled trials need to be conducted with standardized treatment and use. Since serum components are partially similar to tear components, autologous serum eye drops improve dry eye by supplying tear components such as growth factors, proteins, and vitamins. Adding to the evidence based on the treatment of dry eye, we have found a new treatment candidate from serum: selenoprotein P (SeP). The efficacy of SeP as a treatment for dry eye was revealed by applying SeP eye drops to a dry eye rat model. Compared with phosphate-buffered saline treatment, SeP eye drops significantly reduced the fluorescein score of the cornea and suppressed the oxidative stress in the cornea, which is related to onset of dry eye, leading to improved corneal disorder. We have developed a new dry eye model caused by oxidative stress that will be used to screen candidate molecules for antioxidative activity. © 2018 The Authors.
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| 86.
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Higuchi, Akihiro ; Erina Oonishi ; Kawakita, Tetsuya ; Tsubota, Kazuo ; 樋口, 明弘
概要:
金沢大学先端科学・社会共創推進機構<br />Purpose: 2-hydroxy estradiol (2-OHE2) is a catechol derivative of 17β -Estradiol (E2) and it is s
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ynthesized from E2 catalyzed by cytochrome P4501A1. Previous studies reported that 2-OHE2 is a physiologic antioxidant in lipoproteins, liver microsomes, and the brain. Catechol derivatives show an anti-inflammatory effect through the inhibition of prostaglandin endoperoxide synthase (PGS) activity. Corneal erosion caused by dry eye is related to an increase in oxidative stress and inflammation in ocular surface cells. We investigated the therapeutic effects of 2-OHE2 on corneal damage caused by dry eye. Methods: Steroidal radical scavenging activity was confirmed through the electron spin resonance (ESR) method. PGS activity was measured using the COX Fluorescent Activity Assay Kit. To evaluate the effect of 2-OHE2 on the treatment for dry eye, 2-OHE2 was applied as an eye drop experiment using dry eye model rats. Results: 2-OHE2 scavenged tyrosyl radical and possibly suppressed oxidative stress in corneal epithelial cells. In addition, 2-OHE2 inhibited PGS activity, and 2-OHE2 is probably a competitive inhibitor of PGS. Corneal PGS activity was upregulated in the dry eye group. Therefore, 2-OHE2 eye drops improved corneal erosion in dry eye model rats. Conclusions: 2-OHE2 is a candidate for the treatment of dry eye through the suppression of inflammation and oxidative stress in the cornea. © 2016 Molecular Vision.
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| 87.
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Higuchi, Akihiro ; Kawakita, Tetsuya ; Tsubota, Kazuo ; 樋口, 明弘
概要:
金沢大学先端科学・社会共創推進機構<br />Purpose: To investigate the effect of desiccation on secretion of inflammatory cytokines in corne
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al epithelial cells and in the rat desiccation model. Methods: A human corneal epithelial cell line (CEPI) was grown in keratinocyte growth medium 2 (KGM2) to approximately 80% confluence. The medium was aspirated and dishes were left for 0 to 30 min with the cover left open to dry the cells (short-term desiccation). After desiccation, KGM2 was added to the dishes and collected from the dishes 15 min later to measure the concentrations of cytokines in the medium by sandwich enzyme immunoassay (ELISA). Viability of the cells was estimated with alamer blue. To study the effect of long-term desiccation, cultivated cells on transwells were used. After dessiccation for up to 8 h, the viability of the cells and levels of cytokines in the culture medium were examined. The expression of cytokines in the cornea of the dry eye model rat was measured by real-time PCR. Results: Short-term dessication of CEPI cells significantly increased the interleukin (IL)-6 level and slightly increased the tumor necrosis factor (TNF)-α level. Anti-IL-6 antibody partially suppressed cell death caused by desiccation. Upon long-term desiccation, IL-6 and IL-8 levels were increased. In the dry eye model rats, the IL-6 mRNA level in the cornea significantly increased, whereas TNF-α mRNA level slightly increased. Conclusions: Desiccation induced IL-6 expression in corneal epithelial cells, suggesting that IL-6 participates in desiccation-induced cell death. © 2011 Molecular Vision.
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| 88.
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Higuchi, Akihiro ; Inoue, Hiroyoshi ; Kawakita, Tetsuya ; Ogishima, Tadashi ; Tsubota, Kazuo ; 樋口, 明弘
概要:
金沢大学先端科学・社会共創推進機構<br />The ocular surface is strongly affected by oxidative stress, and anti-oxidative systems are maint
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ained in corneal epithelial cells and tear fluid. Dry eye is recognized as an oxidative stress-induced disease. Selenium compound eye drops are expected to be a candidate for the treatment of dry eye. We estimated the efficacy of several selenium compounds in the treatment of dry eye using a dry eye rat model. All of the studied selenium compounds were uptaken into corneal epithelial cells in vitro. However, when the selenium compounds were administered as eye drops in the dry eye rat model, most of the selenium compounds did not show effectiveness except for Se-lactoferrin. Se-lactoferrin is a lactoferrin that we prepared that binds selenium instead of iron. Se-lactoferrin eye drops suppressed the up-regulated expression of heme oxygenase-1, cyclooxygenase-2, matrix metallopeptidase-9, and interleukin-6 and also suppressed 8-OHdG production in the cornea induced by surgical removal of the lacrimal glands. Compared with Se-lactoferrin, apolactoferrin eye drops weakly improved dry eye in high dose. The effect of Se-lactoferrin eye drops on dry eye is possibly due to the effect of selenium and also the effect of apolactoferrin. Se-lactoferrin is a candidate for the treatment of dry eye via regulation of oxidative stress in the corneal epithelium. © 2012 Higuchi et al.
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| 89.
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Higuchi, Akihiro ; Takahashi, Kazuhiko ; Hirashima, Masaki ; Kawakita, Tetsuya ; Tsubota, Kazuo ; 樋口, 明弘
概要:
金沢大学先端科学・社会共創推進機構<br />The ocular surface is always attacked by oxidative stress, and cornea epithelial cells are suppos
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ed to have their own recovery system against oxidative stress. Therefore we hypothesized that tears supply key molecules for preventing oxidative stress in cornea. The potential target key molecule we focused is selenoprotein P (SeP). SeP is a carrier of selenium, which is an essential trace element for many animals, for oxidative stress metabolism in the organism, and was extremely expressed in lacrimal gland. An experiment was performed with SeP eye drops in a rat dry eye model, prepared by removing the lacrimal glands. The anticipated improvement in corneal dry eye index and the suppression of oxidative stress markers were observed in SeP eye drop group. Furthermore, the concentration of SeP was significantly higher in dry eye patients compared with normal volunteers. Collectively, we concluded that tear SeP is a key molecule to protect the ocular surface cells against environmental oxidative stress. © 2010 Higuchi et al.
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| 90.
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Higuchi, Akihiro ; Inoue, Hiroyoshi ; Kaneko, Yoshio ; Oonishi, Erina ; Tsubota, Kazuo ; 樋口, 明弘
概要:
金沢大学先端科学・社会共創推進機構<br />The ocular surface is strongly affected by oxidative stress, which causes many ocular diseases in
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cluding dry eye. Previously, we showed that selenium compounds, e.g., selenoprotein P and Se-lactoferrin, were candidates for treatment of dry eye. This paper shows the efficacy of Se-lactoferrin for the treatment of dry eye compared with Diquas as a control drug using two dry eye models and incorporation of lactoferrin into corneal epithelial cells via lactoferrin receptors. We show the efficacy of Se-lactoferrin eye drops in the tobacco smoke exposure rat dry eye model and short-term rabbit dry eye model, although Diquas eye drops were only effective in the short-term rabbit dry eye model. These results indicate that Se-lactoferrin was useful in the oxidative stress-causing dry eye model. Se-lactoferrin was taken into corneal epithelium cells via lactoferrin receptors. We identified LRP1 as the lactoferrin receptor in the corneal epithelium involved in lactoferrin uptake. Se-lactoferrin eye drops did not irritate the ocular surface of rabbits. Se-lactoferrin was an excellent candidate for treatment of dry eye, reducing oxidative stress by a novel mechanism. © 2016 The Author(s).
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| 91.
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Yamaguchi, Naoya ; Ishii, Fumiyuki ; 山口, 直也 ; 石井, 史之
概要:
金沢大学ナノマテリアル研究所<br />We investigate the effect of tensile strain on spin splitting at the n-type interface of LaAlO3/SrTi
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O3 in terms of spin–orbit coupling coefficient α and spin texture in the momentum space using first-principles density-functional calculations. Our results show that α could be controlled by the tensile strain, and can be enhanced by up to 5 times for a tensile strain of 7%, and the effect of the tensile strain leads to a persistent spin helix, which has a long spin lifetime. The strain effect on the LaAlO3/SrTiO3 interface is important for various applications such as spin field-effect transistors and spin-to-charge conversion.
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| 92.
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Naito, Hisamichi ; Takara, Kazuhiro ; Wakabayashi, Taku ; Kawahara, Hiroki ; Kidoya, Hiroyasu ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />It is widely accepted that blood vessels in the tumor microenvironment are immature because mural ce
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ll (MC) adhesion to endothelial cells (ECs) is broadly lacking. Hyperpermeability of the tumor vasculature then results in interstitial hypertension that mitigates against penetration of anticancer drugs into the depths of the tumor. It has been suggested that treatment with angiogenesis inhibitors normalizes blood vessels, resulting in restoration of normal permeability and improved drug delivery. However, recent reports suggest that cancer cell invasion is induced from the edge of the tumor into peripheral areas after treatment with angiogenesis inhibitors. Therefore, it is important to assess the status of blood vessels in the fibrous cap at the tumor rim after antiangiogenesis therapy. In the present study, we found that mature blood vessels in which ECs are covered with MCs are present in the fibrous cap. After treatment with angiogenesis inhibitors, immature blood vessels were destroyed and vascular function was significantly improved, but maturing blood vessels in which ECs were covered with MCs remained visible. These maturing blood vessels showed a less dilated character after treatment with the angiogenesis inhibitors. It is widely accepted that well-matured blood vessels are sheathed in extracellular matrix (ECM) and that cancer cells migrate along tracks made of ECM collagen fibers. Therefore, our data indicate the importance of destroying maturing blood vessels outside the tumor parenchyma to prevent cancer cell invasion. © 2011 Japanese Cancer Association.
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| 93.
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Iba, Tomohiro ; Naito, Hisamichi ; Shimizu, Shota ; Rahmawati, Fitriana Nur ; Wakabayashi, Taku ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
Background: During sprouting angiogenesis, stalk cells, localized behind tip cells, generate endothelial cells (ECs) for
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the elongation of new vessels. We hypothesized that stalk cells may have endothelial progenitor cell properties because of their highly proliferative ability. We conducted Hoechst dye DNA staining in ECs of preexisting blood vessels from hind limb muscle and found that endothelial-side population (E-SP) cells, which efflux Hoechst rapidly with abundant ABC transporters, show highly producing ability of ECs. We previously showed the existence of E-SP cells in hind limb muscle, retina, and liver, but not in other tissues such as adipose tissue, skin, and placenta. Methods: We investigated the existence of E-SP cells and analyzed their proliferative ability among CD31+CD45- ECs from adipose tissue, skin, and placenta of adult mice. We also analyzed the neovascular formation of E-SP cells from adipose tissue in vivo. Results: We detected E-SP cells in all tissues examined. However, by in vitro colony formation analysis on OP9 cells, we found that E-SP cells from adipose tissue and skin, but not from placenta, have highly proliferative ability. Moreover, E-SP cells from adipose tissue could contribute to the neovascular formation in hind limb ischemia model. Conclusion: The adipose tissue and skin are available sources to obtain endothelial stem cells for conducting therapeutic angiogenesis in regenerative medicine. © 2019 The Author(s).
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| 94.
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Wakabayashi, Taku ; Naito, Hisamichi ; Takara, Kazuhiro ; Kidoya, Hiroyasu ; Sakimoto, Susumu ; Oshima, Yusuke ; Nishida , Kohji ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
Purpose. The neovascular form of age-related macular degeneration (AMD) is characterized by the growth of abnormal new b
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lood vessels from the choroid, termed choroidal neovascularization (CNV). The origin of the new vessels in CNV, however, has not been elucidated fully to our knowledge. The purpose of this study is to identify vascular endothelial side population (SP) cells in the preexisting choroidal vessels, and investigate their potential role in AMD. Methods. We made single cell suspensions of freshly isolated mouse choroidal, retinal, and brain tissue by enzymatic digestion. Vascular endothelial SP cells were isolated using flow cytometry based on the ability to efflux the DNA-binding dye, Hoechst 33342, via ATP-binding cassette (ABC) transporters. Results. In the choroid, 2.8% of CD31+CD45- vascular endothelial cells (ECs) showed a typical SP staining pattern. They were not bone marrow-derived and possessed high colony-forming capacity in vitro. They proliferated during laser-induced CNV in vivo. In contrast, stereotypic SP staining pattern was not observed in retinal and brain ECs. Retinal and brain EC-SP cells included increased SP populations with less colony-forming capacity within the SP compartment, because they contained cells with and without proliferative potential. The latter still could efflux the dye due to high levels of ABC transporters, such as ABCB1a, ABCC4, and ABCC6. Conclusions. The EC-SP cells in the choroid may represent vessel-residing endothelial stem/progenitor cells contributing mainly to angiogenesis, and may be useful for augmenting vascular regeneration or for developing new antiangiogenic therapy in AMD. © 2013 The Association for Research in Vision and Ophthalmology, Inc.
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| 95.
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Yamakawa, Daishi ; Kidoya, Hiroyasu ; Sakimoto, Susumu ; Jia, Weizhen ; Naito, Hisamichi ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />Tie2 is a receptor tyrosine kinase expressed on vascular endothelial cells (ECs). It has dual roles
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in promoting angiogenesis and stabilizing blood vessels, and it has been suggested that Tie2 forms dimers and/or oligomers in the absence of angiopoietin-1 (Ang1); however, the mechanism of ligand-independent dimerization of Tie2 and its biological significance have not been clarified. Using a bimolecular fluorescence complementation assay and a kinase-inactive Tie2 mutant, we show here that ligand-independent Tie2 dimerization is induced without Tie2 phosphorylation. Moreover, based on the fact that Tie1 never forms heterodimers with Tie2 in the absence of Ang1 despite having high amino acid sequence homology with Tie2, we searched for ligand-independent dimerization domains of Tie2 by reference to the difference with Tie1. We found that the YIA sequence of the intracellular domain of Tie2 corresponding to the LAS sequence in Tie1 is essential for this dimerization. When the YIA sequence was replaced by LAS in Tie2 (Tie2YIA/LAS), ligand-independent dimer was not formed in the absence of Ang1. When activation of Tie2YIA/LAS was induced by a high dose of Ang1, phosphorylation of Tie2 was limited compared with wild-type Tie2, resulting in retardation of activation of Erk downstream of Tie2. Therefore, these data suggest that ligand-independent dimerization of Tie2 is essential for a strong response upon stimulation with high dose Ang1. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
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| 96.
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Kidoya, Hiroyasu ; Muramatsu, Fumitaka ; Shimamura, Teppei ; Jia, Weizhen ; Satoh, Takashi ; Hayashida, Yumiko ; Naito, Hisamichi ; Kunisaki, Yuya ; Arai, Fumio ; Seki, Masahide ; Suzuki, Yutaka ; Osawa , Tsuyoshi ; Akira , Shizuo ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />The balance between self-renewal and differentiation of hematopoietic stem and progenitor cells (HSP
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Cs) maintains hematopoietic homeostasis, failure of which can lead to hematopoietic disorder. HSPC fate is controlled by signals from the bone marrow niche resulting in alteration of the stem cell transcription network. Regnase-1, a member of the CCCH zinc finger protein family possessing RNAse activity, mediates post-transcriptional regulatory activity through degradation of target mRNAs. The precise function of Regnase-1 has been explored in inflammation-related cytokine expression but its function in hematopoiesis has not been elucidated. Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA. In addition, we found that dysfunction of Regnase-1 leads to the rapid onset of abnormal hematopoiesis. Thus, our data reveal that Regnase-1-mediated post-transcriptional regulation is required for HSPC maintenance and suggest that it represents a leukemia tumor suppressor. © 2019, The Author(s).
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| 97.
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Kawahara, Hiroki ; Naito, Hisamichi ; Takara, Kazuhiro ; Wakabayashi, Taku ; Kidoya, Hiroyasu ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />Background:A drug delivery system specifically targeting endothelial cells (ECs) in tumors is requir
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ed to prevent normal blood vessels from being damaged by angiogenesis inhibitors. The purpose of this study was to investigate whether apelin, a ligand for APJ expressed in ECs when angiogenesis is taking place, can be used for targeting drug delivery to ECs in tumors.Methods and Results:Uptake of apelin via APJ stably expressed in NIH-3T3 cells was investigated using TAMRA (fluorescent probe)-conjugated apelin. Both long and short forms of apelin (apelin 36 and apelin 13) were taken up, the latter more effectively. To improve efficacy of apelin- liposome conjugates, we introduced cysteine, with its sulfhydryl group, to the C terminus of apelin 13, resulting in the generation of apelin 14. In turn, apelin 14 was conjugated to rhodamine-encapsulating liposomes and administered to tumor-bearing mice. In the tumor microenvironment, we confirmed that liposomes were incorporated into the cytoplasm of ECs. In contrast, apelin non-conjugated liposomes were rarely found in the cytoplasm of ECs. Moreover, non-specific uptake of apelin-conjugated liposomes was rarely detected in other normal organs.Conclusions:ECs in normal organs express little APJ; however, upon hypoxic stimulation, such as in tumors, ECs start to express APJ. The present study suggests that apelin could represent a suitable tool to effectively deliver drugs specifically to ECs within tumors. © 2013 Kawahara et al.
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| 98.
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Sakimoto, Susumu ; Kidoya, Hiroyasu ; Kamei, Motohiro ; Naito, Hisamichi ; Yamakawa, Daishi ; Sakaguchi, Hirokazu ; Wakabayashi, Taku ; Nishida, Kohji ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />Purpose: Adrenomedullin (ADM) has been shown to take part in physiological and pathological angiogen
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esis. The purpose of this study was to investigate whether ADM signaling is involved in choroidal neovascularization (CNV) using a mouse model. Methods and Results: CNV was induced by laser photocoagulation in 8-week-old C57BL/6 mice. ADM mRNA expression significantly increased following treatment, peaking 4 days thereafter. The expression of ADM receptor (ADM-R) components (CRLR, RAMP2 and RAMP 3) was higher in CD31+CD45- endothelial cells (ECs) than CD31-CD45- non-ECs. Inflammatory stimulation upregulated the expression of ADM not only in cell lines but also in cells in primary cultures of the choroid/retinal pigment epithelium complex. Supernatants from TNFα-treated macrophage cell lines potentiated the proliferation of ECs and this was partially suppressed by an ADM antagonist, ADM (22-52). Intravitreous injection of ADM (22-52) or ADM neutralizing monoclonal antibody (mAb) after laser treatment significantly reduced the size of CNV compared with vehicle-treated controls (p<0.01). Conclusions: ADM signaling is involved in laser-induced CNV formation, because both an ADM antagonist and ADM mAb significantly inhibited it. Suppression of ADM signaling might be a valuable alternative treatment for CNV associated with age-related macular degeneration. © 2013 Sakimoto et al.
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| 99.
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Ryu Kanzaki, ; Naito, Hisamichi ; Kise, Kazuyoshi ; Takara, Kazuhiro ; Eino, Daisuke ; Minami, Masato ; Shintani, Yasushi ; Funaki, Soichiro ; Kawamura, Tomohiro ; Kimura, Toru ; Okumura, Meinoshin ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />Alterations to the tumor stromal microenvironment induced by chemotherapy could influence the behavi
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or of cancer cells. In the tumor stromal microenvironment, cancer-associated fibroblasts (CAFs) play an important role. Because the receptor tyrosine kinase Axl and its ligand Gas6 could be involved in promoting non-small cell lung cancer (NSCLC), we investigated the role of Gas6 secreted by CAFs during chemotherapy in NSCLC. In a murine model, we found that Gas6 expression by CAFs was upregulated following cisplatin treatment. Gas6 expression might be influenced by intratumoral hypoperfusion during chemotherapy, and it increased after serum starvation in a human lung CAF line, LCAFhTERT. Gas6 is associated with LCAFhTERT cell growth. Recombinant Gas6 promoted H1299 migration, and conditioned medium (CM) from LCAFhTERT cells activated Axl in H1299 cells and promoted migration. Silencing Gas6 in LCAFhTERT reduced the Axl activation and H1299 cell migration induced by CM from LCAFhTERT. In clinical samples, stromal Gas6 expression increased after chemotherapy. Five-year disease-free survival rates for patients with tumor Axl- and stromal Gas6-positive tumors (n = 37) was significantly worse than for the double negative group (n = 12) (21.9% vs 51.3%, p = 0.04). Based on these findings, it is presumed that Gas6 derived from CAFs promotes migration of Axl-expressing lung cancer cells during chemotherapy and is involved in poor clinical outcome. © 2017 The Author(s).
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| 100.
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Yoshida, Mari ; Ishioka, Yukichi ; Ozawa, Takamasa ; Okuyama, Hirohisa ; Iguchi, Motofumi ; Ota, Takeshi ; Ito, Takaomi ; Nagira, Morio ; Morita, Atsushi ; Tanaka, Hidekazu ; Naito, Hisamichi ; Kidoya, Hiroyasu ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />Partner of sld five 1 (PSF1) is an evolutionary conserved DNA replication factor involved in DNA rep
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lication in lower species, which is strongly expressed in normal stem cell populations and progenitor cell populations. Recently, we have investigated PSF1 functions in cancer cells and found that PSF1 plays a significant role in tumour growth. These findings provide initial evidence for the potential of PSF1 as a therapeutic target. Here, we reveal that PSF1 contains an immunogenic epitope suitable for an antitumour vaccine. We analysed PSF1 peptides eluted from affinity-purified human leukocyte antigen (HLA) by mass spectrometry and identified PSF179-87 peptide (YLYDRLLRI) that has the highest prediction score using an in silico algorithm. PSF179-87 peptide induced PSF1-specific cytotoxic T lymphocyte responses such as the production of interferon-γ and cytotoxicity. Because PSF1 is expressed in cancer cell populations and highly expressed in cancer stem cell populations, these data suggest that vaccination with PSF179-87 peptide may be a novel therapeutic strategy for cancer treatment. © 2017 The Author(s).
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