令和元年度
島根大学医学部研究交流会

日時：2019 年 10 月 18 日（金）18:00 – 19:30

場所：ラパン

日時：2019 年 10 月 23 日（水）場所: 国際交流ラウンジ

1

18:00 – 19:30

日時：2019 年 10 月 18 日（金）18:00 – 19:30

場所：ラパン

ポスター番号：発表・討議時間（８分）
座長：飯笹久18-1

先生（微生物学）

18:00 – 18:08
大腸がんに対する複合的抗がん化学免疫療法(Combined anti-cancer

chemoimmunotherapy against colon cancer) ：谷浦隆仁：消化器・総合外科

18-2

18:08 – 18:16
Application of a Bioactive/Bioresorbable Three-Dimensional Porous Uncalcined andUnsintered Hydroxyapatite/Poly-D/L-lactide Composite with Human Mesenchymal StemCells for Bone Regeneration in Maxillofacial Surgery: A Pilot Animal Study：SHA JING
JING：Department of Oral and Maxillofacial Surgery

18-3

18:16 – 18:24
Bone Regeneration Potential of Uncalcined and Unsintered Hydroxyapatite/Poly L-lactide
Bioactive/Osteoconductive Sheet Used for Maxillofacial Reconstructive Surgery: An In Vivo
Study：Dong Ngoc Quang：artment of Oral and Maxillofacial Surgery

18-4

18:24 – 18:32
Feasibility of a Three-Dimensional Porous Uncalcined and Unsintered Hydroxyapatite/polyD/L-lactide Composite as a Regenerative Biomaterial in Maxillofacial Surgery： BAIYUNPENG：Department of Oral and Maxillofacial Surgery

座長：岡本貴行
18-5

先生（薬理学）

18:32 – 18:40
EBV 陽性頭頸部腫瘍細胞において miR-BART-X は VHL を標的とし HIF-1 を介して解糖経路を活性化する：飯笹久：微生物学講座

18-6

18:40 – 18:48
非アルコール性脂肪性肝疾患の病態形成に関与する miRNA の同定：
岡本貴行：薬理学講座

2

18-7

18:48 – 18:56
血管内皮細胞の硬さとその役割：岡本貴行：薬理学講座

18-12

18:56 – 19:04
The role of Helicobacter pylori infection in the development of Epstein-Barr virus-associatedgastric cancer：Sintayehu Fekadu Kebede：Department of Microbiology 微生物学講座＜10 月研究紹介ポスター＞
18-8

19:04 – 19:12
Ubiquitin-like protein MNSFβ is disaggregated and regulates cell proliferation：.

野津香織：地域医学共同研究部門＜Shimane Journal of Medical Science 2017 優秀学術論文＞
18-9（最優秀学術論文) Effects of Kampo Formulas on Differentiation and Proinflammatory
Cytokines Expression of 3T3-L1 Cells（発生生物学）Qing YAN (顔⻘), Noriko OGAWA,
Akihiro MATSUMOTO, Yuqi DANG, Hiroki OTANI

18-10（優秀学術論文）Protection of Rat Retina against Light-induced Damage by Intraperitoneal and
Oral Administration of a Polyphenol Fraction from Seed Shells of Japanese Horse Chestnuts(Aesculus turbinata BLUME)（眼科学）Tomoe ISHIHARA (石原朋恵), Sachiko KAIDZU,
Hideto KIMURA, Yasuro KOYAMA, Yotaro MATSUOKA, Akihiro OHIRA

18-11（優秀学術論文）Neuro-otological examinations in Patients with Spinocerebellar Degeneration（耳鼻咽喉科学）Michiko SHIBATA (柴田美智子), Ryoji HAMAMURA, Noriaki AOI,
Mitsuhiro KIMURA, Shuhei YAMAGUCHI, Hideyuki KAWAUCHI3

日時：2019 年 10 月 23 日

18:00 – 19:30（グループ１）座長：桑子賢一郎

場所: 国際交流ラウンジ

先生（神経・筋肉生理学）

ポスター番号：発表・討議時間（８分）
23-1

18:00 – 18:08

Evaluation of the functional effects of genetic variants‒missense and nonsense SNPs, indelsand copy number variations‒in the gene encoding human deoxyribonuclease I potentially
implicated in autoimmunity：Akari Kusaka：Department of Legal Medicine

23-2

18:08 – 18:16

Establishment of wheat peroxidase I-specific IgE test to identify wheat-dependent exerciseinduced anaphylaxis developed by sensitization to grass pollen：Ryohei Ogino：Departmentof Dermatology

23-3

18:16 – 18:24

Prevalence of sensitization to galactose-a-1,3-galactose in Tokyo is comparable to that in
Shimane：Yusei Nakagawa：Department of Dermatology

23-4

18:24 – 18:32

A case of macropapular exanthema with pancytopenia showing undetectable serum TARC level：Yasuyuki Ochi：Department of Dermatology
23-5

18:32 – 18:40
Electrical Impedance Tomography を用いて体位による換気分布の変化を観察した心臓血管外科術後の一例：佐藤23-6

慎也：島根大学医学部附属病院リハビリテーション部

18:40 – 18:48
The Assesments of the Effects of NinjinYoeito (Herbal Medice) on Gunn rats: a possible
hyperbilirubinemia-induced animal model of schizophrenia：Muhammad Alim Jaya：
Department of Psychiatry

23-7

18:48 – 19:04
L-アルギニン補充は抗がん剤と免疫チェックポイント阻害による複合免疫療法の抗がん効果を増強する(Supplementation of L-arginine augments antitumor effects induced bychemotherapy and immune checkpoint blockade therapy)：佐藤悠介

免疫学

Department of Immunology

4

Yusuke Sato ：（グループ２）座長：宮城聡

先生（生命科学生物学）

ポスター番号：発表時間（８分）
23-8

18:00 – 18:08
抗がん剤により老化に陥った乳がん細胞の免疫細胞による細胞傷害に対する異なる感 受 性 (Different sensitivities of chemotherapy-induced senescent breast cancer cells toimmune cell-mediated cytotoxicity)：小谷仁司：免疫学

23-9

18:08 – 18:16
CCL19 発現間葉系細胞の局所投与による新規抗がん免疫療法の確立(A novelimmunotherapy by local injection of CCL19-expressing mesenchymal stem cells using
mouse model)：飯田

23-10

雄一：免疫学

18:16 – 18:24
Primary Study on the Role of Nna1 Mutation in the Cerebellar Development of Mouse with
Ataxia and Male Sterility：Pang Bo：Pathology

23-11

18:24 – 18:32

Interkinetic nuclear migration in the trachea and esophageal epithelia of the mouse embryo.

：Regassa Dereje Getachew：Department of Developmental Biology, 発生生物学
23-12

18:32 - 18:40
Histological analysis of the epithelial lumen, mesenchyme and muscle cell layer in the mouse
developing duodenum.：Jahan Nusrat：発生生物学

23-13

18:40 – 18:48
医学研究における「Public Health」の重要性と必要性：研究費の取り方、留学の仕方：そのコツお教えします。
：

廣瀬

昌博：

医学部地域医療政策学講座（附属病院医療安全管理部）

23-14

18:48 – 18:56

Maternal nutritional status during pregnancy in Shimane Prefecture : Fourth report- A comparison by meal skipping - ： 籠橋有紀子：島根県立大学看護栄養学部

23-15

18:56 – 19:04

Maternal nutritional status during pregnancy in Shimane Prefecture : Second report- Comparison among early, middle and late pregnancy – : 中谷陽子：島根県立大学

看護栄養学部5

＜発表者へ＞・ ポスターサイズ：縦 1.3 m X 幅 1.0 m 以内
A poster size must be within 1.3 m high X 1.0 m wide.

・ 17:30-17:55 の間にポスターを貼ってください。この時間帯に貼ることができない者は前もって免疫学講座にポスターを預けておいてください。
Please put up a poster during 17:30 – 17:55. Unless, deposit your poster to the Department
of Immunology in advance.

・ 発表形式：指定された時間（8 分）のポスター前で発表・討議
Each presentation/discussion has 8 min.

・ この研究交流会への出席は大学院講義への出席とみなされます。出席した大学院生は教官にサインをもらってください。
Attending to this meeting can be regarded as that to a lecture for post-graduate students.
Have a sign of teachers.

6

２０１９年１０月１８日（金曜日）

１８－１

発表者：

大学院生 ■

大学院生以外 ☐タイトル (title)：大腸がんに対する複合的抗がん化学免疫療法

Combined anti-cancer

chemoimmunotherapy against colon cancer

発表者 (presenters)：谷浦隆仁

Takahito Taniura

所属 (affiliation)：島根大学医学部

消化器・総合外科

Department of Digestive and General Surgery

メールアドレス（address）: taniura@med.shimane-u.ac.jp

抄録 (abstract)
ある種の抗がん化学療法剤は直接的な殺細胞効果だけでなく、担がん宿主の抗がん免疫を賦活・修飾することが知られている。今回、マウス CT26 大腸がんを皮下接種した同系腫
瘍モデルを用いて、臨床で大腸がんに対する標準的化学療法剤として使用されている 5-FUと L-OHP を併用投与した場合の抗がん免疫応答に及ぼす影響、また、調節性 T (Treg) 細胞を抑制することが知られている抗がん化学療法剤 cyclophosphamide（CP）と 3 剤を併用した場合の治療効果を検証した。担がん 10 日目と 18 日目に抗がん剤を投与した場合、5-FU/LOHP 2 剤併用または CP 単剤の群と比較し、3 剤を併用した群で有意な CT26 の増殖抑制が観察され、半数のマウスで CT26 が完全退縮した。しかし、ヌードマウスではこのような併用効果を認めなかった。複合的抗がん化学免疫療法で CT26 が治癒したマウスでは CT26 の再接種に対して防御免疫が誘導され、また、脾細胞から CT26 特異的細胞傷害性 T 細胞
(CTL) を誘導できた。さらに、3 剤を併用した群ではがん局所において CTL の浸潤促進と単球系骨髄由来抑制性細胞 (MDSC)の減少が観察された。以上の結果から、3 種の抗がん
化学療法剤による複合的抗がん化学免疫療法は、大腸がんに対して有効な免疫療法になる可能性が示された。

7

１８－２
発表者：

大学院生 ■

大学院生以外 ☐タイトル (title)：Application of a Bioactive/Bioresorbable Three-Dimensional
Porous Uncalcined and Unsintered Hydroxyapatite/Poly-D/L-lactide Composite with
Human Mesenchymal Stem Cells for Bone Regeneration in Maxillofacial Surgery: A
Pilot Animal Study
発表者 (presenters)：SHA JING JING
所属 (affiliation)：Department of Oral and Maxillofacial Surgery
メールアドレス（address）: 396318296@qq.com
抄録 (abstract)
A novel three-dimensional porous uncalcined and unsinteredhydroxyapatite/poly-D/L-lactide (3D-HA/PDLLA) composite demonstrated superior
biocompatibility, osteoconductivity, and plasticity, thereby enabling complex
maxillofacial defect reconstruction. Mesenchymal stem cells (MSCs)—a type ofadult stem cell—have a multipotent ability to differentiate into chondrocytes,
adipocytes, and osteocytes. We previously found that CD90 and CD271 doublepositive cell populations from human bone marrow had high proliferative ability
and differentiation capacity in vitro. In the present study, we investigated theutility of bone regeneration therapy using implantation of 3D-HA/PDLLA loadedwith human MSCs (hMSCs) in mandibular critical defect rats. Microcomputed
tomography (Micro-CT) indicated that implantation of a 3D-HA/PDLLA-hMSCs
composite scaffold improved the ability to achieve bone regeneration comparedwith 3D-HA/PDLLA alone. Compared to the sufficient blood supply in themandibular defection superior side, a lack of blood supply in the inferior sidecaused delayed healing. The use of Villanueva Goldner staining (VG staining)
revealed the gradual progression of the nucleated cells and new bone from thescaffold border into the central pores, indicating that 3D-HA/PDLLA loaded with
hMSCs had good osteoconductivity and an adequate blood supply. These results
further demonstrated that the 3D-HA/PDLLA-hMSCs composite scaffold was aneffective bone regenerative method for maxillofacial boney defectreconstruction.

8

１８－３

発表者：

大学院生 ■

大学院生以外 ☐タ イ ト ル (title) ： Bone Regeneration Potential of Uncalcined and Unsintered
Hydroxyapatite/Poly

L-lactide

Bioactive/Osteoconductive

Sheet

Used

for

Maxillofacial Reconstructive Surgery: An In Vivo Study
発表者 (presenters)：Dong Ngoc Quang
所属 (affiliation)：Department of Oral and Maxillofacial Surgery
メールアドレス（address）:quangbeo87@gmail.com

抄録 (abstract)
Uncalcined and unsintered hydroxyapatite/poly L-lactide (u-HA/PLLA) material has
osteoconductive characteristics and is available for use as a maxillofacial
osteosynthetic reconstruction device. However, its bone regeneration ability inthe maxillofacial region has not been fully investigated. This study is the firstto assess the bone regenerative potential of osteoconductive u-HA/PLLA material
when it is used for repairing maxillofacial bone defects. A total of 21 SpragueDawley male rats were divided into three groups: the u-HA/PLLA, PLLA, or shamcontrol groups. A critical size defect of 4 mm was created in the mandible of eachrat. Then, the defect was covered with either a u-HA/PLLA or PLLA sheet on the
buccal side. The rats in each group were sacrificed at 2, 4, or 8 weeks. The rats'
mandibles were sampled for histological analysis with hematoxylin and eosin
staining, histomorphometry, and immunohistochemistry with Runx2 and osteocalcin(OCN) antibody. The amount of bone formed in the u-HA/PLLA group was significantly
higher than that of the PLLA group. The expression of Runx2 and OCN in the uHA/PLLA group was also significantly higher. These results demonstrate that theu-HA/PLLA material has excellent bone regenerative ability and confirm its
applicability as a reconstructive device in maxillofacial surgery.

9

１８－４
発表者：

大学院生 ■

大学院生以外 ☐タイトル (title)：Feasibility of a Three-Dimensional Porous Uncalcined andUnsintered Hydroxyapatite/poly-D/L-lactide Composite as a Regenerative
Biomaterial in Maxillofacial Surgery
発表者 (presenters)：BAI YUNPENG
所属 (affiliation)：Department of Oral and Maxillofacial Surgery
メールアドレス（address）: xyywq@126.com
抄録 (abstract)
This study evaluated the feasibility of a novel three-dimensional (3D)
porous composite of uncalcined and unsintered hydroxyapatite (u-HA) and poly-D/Llactide(PDLLA)(3D-HA/PDLLA)

for

the

bony

regenerative

biomaterialinmaxillofacial surgery, focusing on cellular activities and osteoconductivity
properties in vitro and in vivo. In the in vitro study, we assessed theproliferation and ingrowth of preosteoblastic cells (MC3T3-E1 cells) in 3DHA/PDLLA biomaterials using 3D cell culture, and the results indicated enhanced
bioactive proliferation. After osteogenic differentiation of those cells on 3DHA/PDLLA, the osteogenesis marker genes runt-related transcription factor-2(Runx2), and Sp7 (Osterix) were upregulated. For the in vivo study, we evaluatedthe utility of 3D-HA/PDLLA biomaterials compared to the conventional bone
substitute of beta-tricalcium phosphate (-TCP) in rats with critical mandibular
bony defects. The implantation of 3D-HA/PDLLA biomaterials resulted in enhancedbone regeneration, by inducing high osteoconductivity as well as higher -TCP
levels. Our study thus showed that the novel composite, 3D-HA/PDLLA, is an
excellent bioactive/bioresorbable biomaterial for use as a cellular scaffold, bothin vitro and in vivo, and has utility in bone regenerative therapy, such as forpatients with irregular maxillofacial bone defects.

10

１８－５

発表者：

大学院生 ☐

大学院生以外 ■タイトル (title)：EBV 陽性頭頸部腫瘍細胞において miR-BART-X は VHL を標的とし HIF1α を介して解糖経路を活性化する
発表者 (presenters)：飯笹久

所属 (affiliation)：微生物学講座
メールアドレス（address）: iizasah@med.shimane-u.ac.jp

抄録 (abstract)
Epstein-Barr ウイルス(EBV)は、上咽頭癌ばかりでなく他の頭頸部腫瘍（HNSCC）の発生にも関わるという報告が増加している。我々は、EBV が持続感染した扁平上皮細胞株を作製した。EBV 陽性扁平上皮細胞株では解糖系が亢進し、乳酸の産生が増加していた。また糖代謝関連遺伝子群の発現を解析すると、EBV 陽性細胞では HIF-1α 分解因子である VHL の発現が低下し、HIF-1α の発現が上昇していた。EBV がコードする miRNA（BART miRNA）は、上皮腫瘍で高発現している。VHL 3’UTR をルシフェラーゼ遺伝子の下流に組み込んだベク
ターを用いると、EBV 陽性細胞では陰性細胞よりもルシフェラーゼ活性が低下した。次に、VHL を標的とする miRNA を探索し、miR-BART-X に注目した。miR-BART-X 特異的阻害剤を用いると、ルシフェラーゼ活性は上昇し、VHL の発現も上昇した。さらに、HIF-1α の発現低下と解糖系遺伝子の発現低下も認めた。miR-BART-X は、VHL を標的とすることで HIF-1α
転写因子のユビキチン分解を抑制し、解糖系の亢進や乳酸産生の増加を導くと考えられた。

11

１８－６

発表者：

大学院生 ☐

大学院生以外 ■タイトル (title)：非アルコール性脂肪性肝疾患の病態形成に関与する miRNA の同定
発表者 (presenters)：岡本貴行
所属 (affiliation)：薬理学講座
メールアドレス（address）:okamoto@med.shimane-u.ac.jp

抄録 (abstract)
肥満やメタボリックシンドロームを原因として非アルコール性脂肪性肝疾患（NAFLD）は発症する。わが国でも検診等の受診者の 30％に脂肪肝がみられ、将来、NAFLD は国民病になりうると予測される。NAFLD 患者は心血管イベントの発症リスクが高く、さらに非アル
コール性脂肪肝炎（NASH）に至ると肝硬変や肝癌など肝関連死が高率となる。これまで NAFLD
およびその関連疾患において発現異常をきたす miRNA の存在が多数報告され、NAFLD の治
療標的分子、または診断分子としての応用が期待されている。
われわれはこれまで NAFLD 患者の肝組織で発現する miRNA の発現解析を行い、正常肝と比較して著しく発現が変動する miRNA を複数見出した。われわれは、NAFLD 肝組織で特に顕著な発現増加がみられる miR-27b に着目し、miR-27b が NAFLD の基礎病態である脂肪蓄積に及ぼす影響を解析した。その結果、miR-27b はマウス 3T3－L1 細胞における脂肪蓄積を促進した。また、miR-27b はミトコンドリアでの脂肪酸代謝に関わるアシル CoA チオエ
ステラーゼ 2(ACOT2)の発現を誘導した。ACOT2 を siRNA で発現低下させると 3T3－L1 細胞における脂肪蓄積は抑制された。
以上の結果から、NAFLD 患者で増加する miR-27b は ACOT2 の発現誘導を介して脂肪蓄積を促進していることを明らかにした。

12

１８－７

発表者：

大学院生 ☐

大学院生以外 ■タイトル (title)：血管内皮細胞の硬さとその役割
発表者 (presenters)：岡本貴行
所属 (affiliation)：薬理学講座
メールアドレス（address）:okamoto@med.shimane-u.ac.jp

抄録 (abstract)
動脈硬化病変では血管組織の線維化や石灰化によって血管硬化（弾性率の増加）が生じる。血管硬化は心血管イベント発生リスクと相関を示し、これらは血管の硬さが血管機能に及ぼす可能性を示唆する。一方で、細胞そのものも固有の硬さを呈するが、細胞の硬さ変化と血管機能の関連については不明な点が多い。本研究で我々は、血管内皮細胞に着目し、炎症時における血管内皮細胞の硬さ変化とその役割を解析した。
細胞の硬さは原子間力顕微鏡を用いて測定した。ヒト臍帯静脈内皮細胞を腫瘍壊死因子で刺激した。刺激 4 時間後に細胞は著しく硬化し、24 時間後には未刺激時と同程度まで軟化した。細胞の硬さは細胞骨格と細胞間相互作用の影響を受ける。細胞の硬化部位でのア
クチンの重合を観察し、硬化部位でアクチンの重合が亢進することを明らかにした。また、細胞間ギャップ結合を阻害した細胞は著しく硬くなることを明らかにした。さらに硬化した血管内皮細胞上への単球の接着を評価した結果、血管内皮細胞の硬さ依存的な単球接着の亢進がみられた。
以上の結果から、炎症時における血管内皮細胞硬化は白血球の接着を亢進し、血管病変形成を促進する可能性が示唆された。

13

１８－１２

発表者：

大学院生 ■

大学院生以外 ☐タイトル (title)：The role of Helicobacter pylori infection in the development of Epstein-Barrvirus-associated gastric cancer

発表者 (presenters)：Sintayehu Fekadu Kebede所属 (affiliation)：微生物学講座

Department of Microbiology

メールアドレス（address）: serkalem@med.shimane-u.ac.jp

抄録 (abstract)
Most of gastric cancer (GC) cases are associated with infection of Helicobacter

pylori (H. pylori). On the other hand, 10% of GC cases detect Epstein-Barr virus(EBV) infection in cancer cells. However, it is unclear that pathophysiologicalinvolvement of H. pylori infection in the development of EBV associated cancer(EBVaGC). To clarify this, gastric epithelial AGS cells were infected with H.

pylori CPY6271 strain. After 7 hours, H. pylori was removed by washing cells withsaline and adding antibiotics to the culture. AGS cells exposed with H. pylori
were infected with recombinant EBV having eGFP gene in its BXLF1 gene (eGFP-EBV).
Establishment of infection was confirmed by fluorescence microscopy and efficiency
of infection was quantified by FACS analysis. AGS cells exposed with H. pylori
was induced with hummingbird phenotype, but viability of cells was not affected.
AGS cells infected with H. pylori were slightly increased with EBV infectivity by
microscopic observation. I am going to quantify change in EBV gene expression by

H. pylori infection. I have also established a protocol to recover high tittered
EBV during the course of my research, which is worth to be reported.

14

１８－８

Ubiquitin-like protein MNSFβ is disaggregated and regulates cell proliferation.

地域医学共同研究部門

野津香織

Shimane Journal of Medical Science 2017 優秀学術論文
１８－９（最優秀学術論文) Effects of Kampo Formulas on Differentiation and Proinflammatory
Cytokines Expression of 3T3-L1 Cells.

（発生生物学）Qing YAN（顔⻘） ,Noriko

OGAWA, Akihiro MATSUMOTO, Yuqi DANG, Hiroki OTANI

１８－１０(優秀学術論文)

Protection of Rat Retina against Light-induced Damage by Intraperitoneal

and Oral Administration of a Polyphenol Fraction from Seed Shells of Japanese Horse Chestnuts(Aesculus turbinata BLUME)

石原

（眼科学）

朋恵 Tomoe ISHIHARA, Sachiko KAIDZU,Hideto KIMURA, Yasuro KOYAMA,

Yotaro MATSUOKA, Akihiro OHIRA

１８－１１(優秀学術論文)

Neuro-otological examinations in Patients with Spinocerebellar Degeneration（耳鼻咽喉科学）柴田美智子 Michiko SHIBATA,

Ryoji HAMAMURA, Noriaki AOI,Mitsuhiro KIMURA, Shuhei YAMAGUCHI,
KAWAUCHI

15

Hideyuki２０１９年１０月２３日（水曜日）
２３－１

発表者： 大学院生 ■ 大学院生以外 ☐タイトル (title)：Evaluation of the functional effects of genetic variants‒missense
and nonsense SNPs, indels and copy number
variations‒in the gene encoding human deoxyribonuclease I potentially implicatedin autoimmunity
発表者 (presenters)：Akari Kusaka
所属 (affiliation)：Department of Legal Medicine, Shimane University School of
Medicine, Enya, Izumo, Japan
メールアドレス（address）:htakeshi@med.shimane-u.ac.jp
抄録 (abstract)
Genetic variants, such as single nucleotide polymorphisms (SNPs), in the
deoxyribonuclease I (DNase I) gene which remarkably reduce or abolish the activity
are assumed to be substantially responsible for the genetic backgrounds
determining susceptibility to autoimmune dysfunction. Here, we exhaustively
evaluated many genetic variants, including missense and nonsense SNPs and indel(inframe) variants in the gene, potentially implicated in autoimmune diseases asfunctional variants resulting in altered activity levels. Accordingly, a total of
60 genetic variants in the DNase 1 gene (DNASE1) inducing abolishment or marked
reduction of the DNase I activity could be identified as genetic risk factors for
autoimmunity, irrespective of how sparsely they were distributed in the population.
It was noteworthy that SNP p.Gln244Arg, reportedly associated with autoimmunity
and reducing the activity to about half of that of the wild type, and SNP
p.Arg107Gly, abolishing the activity completely, were distributed worldwide andin African populations at the polymorphic level, respectively. On the other hand,with regard to copy number variations in DNASE1 where loss of copy leads to a
reduction of the in vivo enzyme
activity, only 2 diploid copy numbers were distributed in Japanese and German
populations, demonstrating no loss of copy.

16

２３－２

発表者：

大学院生 ■

大学院生以外 ☐タイトル (title)：Establishment of wheat peroxidase I-specific IgE test to identify wheatdependent exercise-induced anaphylaxis developed by sensitization to grass pollen

発表者 (presenters)：Ryohei Ogino
所属 (affiliation)：Department of Dermatology
メールアドレス（address）: ryogino@med.shimane-u.ac.jp

抄録 (abstract)
We have identified peroxidase I as a causative allergen for wheat-dependent exercise-induced
anaphylaxis developed as pollen food allergy syndrome (PFAS-WDEIA) due to crossreaction between wheat proteins and grass pollen allergens. The purpose of this study is toestablish peroxidase I-specific IgE test and test its sensitivity and specificity to identify PFASWDEIA.
Serum were obtained from 6 patients with PFAS-WDEIA, 18 patients with conventional
WDEIA, 11 patients with hydrolyzed wheat protein allergy, 17 patients with hay fever, and22 patients with red meat/crustacean allergy. Peroxidase I was purified uponchromatography steps, and peroxidase I-specific IgE test was established by CAP-FEIA
system.
Positive of peroxidase I-specific IgE test were 3 of 6 PFAS-WDEIA patients and 2 of 17 hayfever patients, but none of 18 conventional WDEIA, 11 hydrolyzed wheat allergy, nor 22 redmeat/crustacean allergy patients. Sensitivity and specificity of peroxidase I- and existingallergen-specific IgE tests to identify PFAS-WDEIA patients were calculated as follows; 50%
and 97% for peroxidase I, 83% and 79% for wheat, 50% and 79% for gluten, 0% and 79%
for ω-5 gliadin.
Wheat peroxidase I-specific IgE test is useful to identify patients with wheat-dependent
exercise-induced anaphylaxis developed by sensitization to grass pollen.

17

２３－３

発表者：

大学院生 ■

大学院生以外 ☐タイトル (title)：Prevalence of sensitization to galactose-a-1,3-galactose in Tokyo is comparable
to that in Shimane

発表者 (presenters)：Yusei Nakagawa
所属 (affiliation)：Department of Dermatology
メールアドレス（address）:yuusei@med.shimane-u.ac.jp

抄録 (abstract)
Principal cause of cetuximab-induced anaphylaxis is IgE antibodies against galactose-α-1,3-galactose(α-Gal) present on mouse-derived Fab portion of cetuximab heavy chain. Cetuximab allergy patients
often develop allergic reaction to mammalian meat by reacting α-Gal. In this study, we aimed toclarify sensitization rate in Tokyo, the largest city in Japan and to compare with that in Shimane. We
enrolled 50 subjects in Tokyo Medical and Dental University (TMDU) Hospital, and 100 subjects in
Shimane University Hospital, both of whom were consulted with complaining anything except foodallergy. Serum α-Gal-specific and beef-specific IgE were measured using ImmunoCAP. Specific IgE
to cetuximab was detected by immunoblotting. As a result, the α-Gal-specific IgE were detected (≥0.10 kUa/L) in 16 out of 100 (16%) subjects in Shimane University Hospital and 8 of 50 (16%)
subjects in TMDU Hospital. Moreover, among them, 11 of the 16 in Shimane University Hospitaland 5 of the 8 in TMDU Hospital were positive (≥ 0.35 kUa/L) for the beef-specific-IgE test.
Additionally, immunoblotting showed 5 of 100 subjects (5%) in Shimane University Hospital and 2
subjects (4%) in TMDU Hospital have IgE antibody to cetuximab. Thus, there is almost no differenceof α-Gal sensitization rate between Shimane and Tokyo.

18

２３－４

発表者：

大学院生 ☐

大学院生以外 ■タイトル (title)：A case of macropapular exanthema with pancytopenia showing undetectable
serum TARC level

発表者 (presenters)：Yasuyuki Ochi
所属 (affiliation)：Department of Dermatology
メールアドレス（address）:oddnight@med.shimane-u.ac.jp

抄録 (abstract)
We have already reported that serum serum thymus and activation-regulated chemokine (TARC)
level is extremely high in early stages of drug-induced hypersensitivity syndrome and a goodmarker to differentiate other drug eruptions, especially macropapular exanthema (MPE). We
experienced a case of MPE complicated with pancytopenia which shows undetectable serum TARC
level.
A 54-year-old woman with myelofibrosis consulted our hospital complaining high fever and cough.
Levofloxacin was started for high fever, and the patient developed systemic erythema four days
after the levofloxacin treatment. Her physical examination revealed multiple papular erythema withitch on almost her entire body. MPE was diagnosed, levofloxacin was discontinued, and topicalsteroid therapy was initiated. Her blood examination showed pancytopenia, including WBC count
1990, RBC count 236,000, and platelet count 15,000. Her serum TARC was under detection limit of
100 pg/ml on Day 3, 6, and 13 after onset of her eruptions. The skin rashes disappeared two weeks
after the onset.
With the findings that serum TARC levels have no correlation to platelet counts in 14 cases with
MPE previously examined in our department. Taking this into consider, we concluded that theundetectable serum TARC levels in this case are related to the complication of pancytopenia.

19

２３－５

発表者：

大学院生 ☐

大学院生以外 ■タイトル (title)：Electrical Impedance Tomography を用いて体位による換気分布の変化を観察した心臓血管外科術後の一例
発表者 (presenters)：佐藤慎也

所属 (affiliation)：島根大学医学部附属病院リハビリテーション部
メールアドレス（address）: satoshin@med.shimane-u.ac.jp

抄録 (abstract)【緒言】
Electrical Impedance Tomography（以下、EIT）は非侵襲的に肺の換気分布をリアルタイ
ムにモニタリングすることが可能である。今回、心大血管術後の患者に対し、EIT を用いて体位による換気分布の変化を観察したため報告する。
【症例】
症例は 70 代男性。人工弁機能不全、右冠動脈狭窄に対し大動脈弁置換術及び冠動脈バイパス術を施行した。既往歴に肺気腫があり、％肺活量 86.1%、一秒率 72.7%であった。術後翌日、人工呼吸器を離脱し、呼吸理学療法や段階的な離床を開始した。術後 3 日目に胸部
X 線画像で右優位に胸水の貯留を認めたため、胸水穿刺が施行された。穿刺後、体位の変化（ベッド上臥位、頭高位、端坐位、立位）が換気分布にどのような影響を与えるかを EIT でモニタリングした。その結果、換気分布割合（右肺：左肺）は、ベッド上仰臥位では 11.7％：
88.3％、頭高位では 4.8%：95.2％、端座位では 20.8％：79.2%、立位では 47.0％：53.0％
であった。
【結論】
胸水穿刺後でも換気分布異常は残存し、端座位や立位などの離床は換気分布改善に寄与する可能性がある。

20

２３－６

発表者：

大学院生 ■

大学院生以外 ☐タイトル (title)：The Assesments of the Effects of NinjinYoeito (Herbal medice) on Gunn
rats: a possible hyperbilirubinemia-induced animal model of schizophrenia

発表者 (presenters)：Muhammad Alim Jaya
所属 (affiliation)：Department of Psychiatry
メールアドレス（address）: alimjayam@gmail.com

抄録 (abstract)
Schizophrenia is one of the crucial psychiatric disorders which severely impact on ADL ofpatients. The main treatment of schizophrenia has been antipsychotics since 1960. However, theeffect of antipsychotics is still limited though versatile types of antipsychotics have been launched.
Especially, the effect was limited in the neurocognitive symptoms, rather than positive symptoms,
for example, delusion, hallucination, excitement.
One of the herbal medicine-NinjinYoeito (NYT) has been reported to improve theneurocognitive symptoms of patients of Altheimer’s disease, and also in developmental disorder as
autistic spectrum disorder. In vitro, It has been reported that NYT has the effect enhancing theremyelination accompanied with the suppression of the oxidative stress and neuroinflammation.
Therefore, in the current study, we would like to the test the effect of the NYT on Gunn rats
(congenital hyperbilirubinemic rats) which have the features of schizophrenia, from the viewpointof the both sides of histopathoplogical and behavioral assessments. And we would like to find theclue of the an alternative or adjuvant treatment for schizophrenia.

21

２３－７

発表者：

大学院生 ■

大学院生以外 ☐タイトル (title)：L-アルギニン補充は抗がん剤と免疫チェックポイント阻害による複合免疫療法の抗がん効果を増強する Supplementation of L-arginine augments antitumor effects
induced by chemotherapy and immune checkpoint blockade therapy

発表者 (presenters)：佐藤悠介
所属 (affiliation)：免疫学

Yusuke Sato

Department of Immunology

メールアドレス（address）: styusuke0515@gmail.com

抄録 (abstract)
Myeloid-derived suppressor cells (MDSCs) express arginase I and indoleamine 2,3-dioxygenase andare known to suppress T cell function in tumor-bearing hosts via downregulation of L-arginine andL-tryptophan, respectively. In this study, we examined effects of supplementation of these aminoacids on antitumor effects in CT26 colon carcinoma-bearing mice. Supplementation of L-arginine
showed the tendency to suppress the tumor growth, whereas that of L-tryptophan promoted the tumor
growth. Although combination therapy with cyclophosphamide (CP) and anti-PD-1 antibody
significantly suppressed the tumor growth, no tumor regression was observed. However, additional
supplementation of L-arginine induced complete tumor regression in more than half mice.
Interestingly, LC/MS analysis on the plasma revealed that, although the plasma levels of L-arginine
in CT26-bearing mice were not decreased, CP administration significantly decreased them.
Importantly, supplementation of L-arginine recovered their levels to those of naive mice. These
results suggest that a chemotherapeutic drug CP, but not tumor-bearing state, decreases the level of
L-arginine, and that L-arginine supplementation is effective in anticancer immunotherapy whencombined with chemotherapy.

22

２３－８

発表者：

大学院生 ☐

大学院生以外 ■タイトル (title)：Different sensitivities of chemotherapy-induced senescent breast cancer cells
to immune cell-mediated cytotoxicity 抗がん剤により老化に陥った乳がん細胞の免疫細胞による細胞傷害に対する異なる感受性

発表者 (presenters)：小谷仁司 Hitoshi Kotani
所属 (affiliation)：免疫学 Department of Immunology
メールアドレス（address）: kotani14@med.shimane-u.ac.jp

抄録 (abstract)
Chemotherapeutic drugs induce apoptosis in cancer cells, whereas some cancer cells survive as aresult of DNA damage response with being senescent. Despite growth arrest, senescent cancer cells
promote tumor formation and recurrence by producing cytokines and growth factors, designated as
the senescence-associated secretory phenotype (SASP). In this study, we examined the susceptibilityof senescent human breast cancer cells to immune cell-mediated cytotoxicity. Doxorubicin (DXR)
treatment induced senescence in MDA-MB-231 and BT-549 cells: induced expression of H2AX andSA-gal and enhanced production of proinflammatory cytokines. Importantly, DXR-treatedsenescent MDA-MB-231 cells showed increased sensitivity to two types of immune cell-mediatedcytotoxicity: cytotoxicity of activated CD4+ T cells and ADCC by NK cells. This increased sensitivity
was not observed following treatment with the senescence-inducing CDK4/6 inhibitor, abemaciclib.
These results indicated that DXR and CDK4/6 inhibitor induced senescence in breast cancer cells,
but that they differed in their sensitivity to immune cell-mediated cytotoxicity.

23

２３－９

発表者：

大学院生 ☐

大学院生以外■タイトル (title)：CCL19 発現間葉系細胞の局所投与による新規抗がん免疫療法の確立

Anovel immunotherapy by local injection of CCL19-expressing mesenchymal stem cells using mousemodel

発表者 (presenters)：飯田雄一 Yuichi Iida所属 (affiliation)：免疫学 Department of Immunology
メールアドレス（address）: yiida@med.shimane-u.ac.jp

抄録 (abstract) Mesenchymal stem/stromal cells (MSC) accumulate and reside in tumor sites. Taking
advantage of this feature in anticancer therapy, immortalized murine MSC (iMSC) were geneticallyaltered to produce chemokine (C-C motif) ligand 19 (iMSC/CCL19), which attracts dendritic cells(DC) and T lymphocytes. Co-injection of iMSC/CCL19 into mice significantly suppressed the tumor
growth. Co-injected iMSC/CCL19 survived longer than CCL19-expressing fibroblast (iFib/CCL19)
in the tumor sites. In a therapeutic model, local injection of iMSC/CCL19 suppressed the tumor
growth, and increased IFN-γ+ CD8+ T cell and CCR7+ DC infiltration in tumor site was observed
when treated with iMSC/CCL19, but not with iMSC. This anti-tumor effect was completely negatedby depletion of CD4+ T cells and partially negated by depletion of CD8+ T cells. Furthermore, theanti-tumor effects induced by local injection of iMSC/CCL19 were augmented by additional therapy
with anti-programmed death (PD)-ligand 1 (PD-L1) antibody, but not with anti-PD-1 antibody. This
combination therapy cured most of the tumors in CT26-bearing mice. These results suggest that local
therapy with iMSC/CCL19 can suppress tumor growth via effective recruitment of CCR7+ DC into
tumor sites and increase IFN-γ+ CD8+ T cells, and that combination with anti-PD-L1 antibody therapy
can be a powerful anti-cancer therapy.

24

２３－１０

発表者：

大学院生 ■

大学院生以外 ☐タイトル (title)：Primary Study on the Role of Nna1 Mutation in the Cerebellar Developmentof Mouse with Ataxia and Male Sterility

発表者 (presenters)：Pang Bo
所属 (affiliation)：Pathology
メールアドレス（address）: pangbo@med.shimane-u.ac.jp

抄録 (abstract)
Nna1 gene is phylogenetically-preserved and codes for carboxyl peptidase (CCP) 1. Its
mutation of different types is known to cause a progressive loss of the Purkinje cells (PC).
The ataxia and male sterility (AMS) mouse harboring a point mutation and is the only Nna1allele model. Thus, we investigate ontogenical Nna1 distribution in the cerebellum of the
AMS mice of every genotype from postnatal day P-7 through P-28, mainly before diseasephenotype appears. Provide experimental basis for gene-targeted therapy of cerebellar
development-related diseases. We applied immunohistochemistry and immunofluorescence
using anti-human Nna1 antibodies to investigate its distribution in the cerebellum of AMS
mice of each genotype from postnatal days (P) 7-28. RESULTS: Both the molecular andgranular layers were positive for Nna1. The semi-quantificationthe of Nna1’s stain-strength
revealed in the following order: wild-type, ams-heterozygous, then ams-homozygous.
CONCLUSION: The distribution of the Nna1 in the cerebellum, except in the PCs, of wildtype mice varies according to the age of the mice, while that in the PCs is stable from P15.
However, the loss of PCs might occur due to a protein shortage because the instability of its
3-dimensional structure, which is caused by the Nna1 point mutation.

25

２３－１１

発表者：

大学院生 ■

大学院生以外 ☐タイトル (title)：Interkinetic nuclear migration in the trachea and esophageal epithelia of themouse embryo.

発表者 (presenters)：Regassa Dereje Getachew
所属 (affiliation)：Department of Developmental Biology, 発生生物学
メールアドレス（address）:getachewdereje68@gmail.com

抄録 (abstract)
Interkinetic nuclear migration (INM) is the migration of nuclei of the epithelial cells in synchrony
with cell cycle, undergoing cell division at apical side and back to basal side during interphase. We
investigated the existence, the inter-organ and regional differences of INM pattern in the epithelia oftrachea and esophagus of mouse embryos at E11.5 and E12.5 and the following 12 hrs. The
chronological changes in 5-ethynyl-2’- deoxyuridine (EdU) labeled nuclei along the apico-basal axis
were analyzed. We ran one-way ANOVA using MorphoJ package to analyze the comparison among
the groups. The trachea total vs. esophagus total at E11.5 showed different INM patterns of EdUlabeled nuclei distribution (P = 0.0001), while at E12.5 no differences between the two organs (P =0.0959). Trachea at E11.5 showed regional difference (dorsal vs. ventral) (P = 0.012), while at E12.5
no regional differences (P = 0.302). Esophagus showed no reginal differences at either E11.5 or E12.5(P = 0.694, P = 0.602, respectively). These findings suggest that the inter-organ INM patterndifference exists at E11.5 between trachea and esophagus, and regional difference exists in trachea at
E11.5 but not in esophagus, which may be involved in the later different development of the organs.

26

２３－１２

発表者：

大学院生 ■

大学院生以外 ☐タイトル (title)：Histological analysis of the epithelial lumen, mesenchyme and muscle cell layer
in the mouse developing duodenum.

発表者 (presenters)：Jahan Nusrat
所属 (affiliation)：発生生物学
メールアドレス（address）:

抄録 (abstract)
The mechanism of the development of epithelium, mesenchyme, as well as smooth muscle (SM) layerof the gut during embryogenesis is important to understand whole gut development. Our purpose is
to clarify the common features in the regional difference in the development of the epithelium,
mesenchyme and SM layers of the duodenum for elucidating their possible relationship with theoverall macroscopic morphogenesis of the duodenum. We used C57BL/6 mouse embryos atembryonic day (E) 13.5, 15.5, 17.5 (each day, n=3). By histomorphometric analysis we found that theepithelial lumen is oval and its axis showed a general clockwise rotation against the mesentery at
E13.5. Number of inner circular SM layers At E13.5, E15.5 and E17.5 showed a regional difference
related to the mesentery, but no clear change along the long axis of the duodenum. We also observedthat the epithelial nuclear shape and the adjacent mesenchyme density change along the long axis of
the duodenum, and these epithelial-mesenchymal interactions might contribute to the winding of theduodenum resulting the “C” shape curve. However, these are our current hypotheses at this moment
but need further research to draw any conclusion.

27

２３－１３

発表者：

大学院生 ☐

大学院生以外 ■タイトル (title)： 医学研究における「Public Health」の重要性と必要性：研究費の取り方、留学の仕方：そのコツお教えします。
発表者 (presenters)：

廣瀬

所属 (affiliation)：

医学部地域医療政策学講座（附属病院医療安全管理部）

メールアドレス（address）:

昌博

mhirose@med.shimane-u.ac.jp

抄録 (abstract)
地域医療政策学講座は、疫学・統計学などの社会医学と経済学・経営学などの社会科学を基盤とし、問題提起・解決志向型で、学際的他領域統合的分野であり、医療の有効性、経済性、標準化や質的評価を追求する医療経済学を基盤とし、地域医療、地域包括ケアを研究フィールドとする学問である。このようなことから、地域医療政策学は広義では「Public Health」の一分野である。
しかしながら、わが国では戦後、GHQ によりすべての医学部に「公衆衛生学講座」が設置されたが、「Public Health」の本質が理解されないまま、衛生学講座とともにその姿が医学部から失われつつある。
その一方で、「Public Health」の本質をみなそうとする動きが 2000 年に始まった。京都
大学にわが国初の公衆衛生大学院（School of Public Health）が新設され、2007 年には東京大学、その後帝京大学、聖路加国際大学に設置された。これらは米国 Council on
Education for Public Health に認定されるための基本科目「生物統計学」、「疫学」「医療管理学」「社会・行動科学」および「環境保健科学」を置く必要があり、その数は米国の 30大学に比べわが国ははるかに少ない。このことはわが国が「Public Health」を重視してこなかった証でもある。
発表会では Public Health の必要性とともに研究費の取り方、留学の仕方をお話しします。

28

２３－１４

発表者：

大学院生 ■

タイトル (title)：

大学院生以外 ☐Maternal nutritional status during pregnancy in Shimane Prefecture :Fourth report - A comparison by meal skipping -発表者 (presenters)：籠橋有紀子
所属 (affiliation)：島根県立大学看護栄養学部

抄録 (abstract)【Background】It is reported that the birth rate of low birth weight babies in Shimane prefecture is thethird largest nationwide, and the average of birth weight is reported to be about 30 g less than the national
average, and there is a possibility of various risks in the future of the babies.
【Purpose】We investigate nutritional intake situation, dietary behavior, and food consciousness ofpregnant women in Shimane Prefecture and we are studying the relevance to birth weight of babies.
【Methods】In this study, we examined the frequency of food intake in 26 pregnant women from 10 to 12
weeks (early), around 26 weeks (middle) and 36 weeks (late), and compared the nutrient intake by thedifference in the state of meal skipping (skipped vs non-skipped) during pregnancy and birth weight ofbabies.
【Results & Discussion】In the early pregnancy group, 38.4% of pregnant women skipped meals morethan once a week, and it was suggested that many of the nutrients were less than the amount recommended
by the Ministry of Health, Labour and Welfare, Japan. In the middle and late pregnancy groups, 23.0%
and 30.7% of pregnant women skipped meals more than once a week, respectively. The average of birthweight of babies were 2993.3 ± 384.1 grams in the non-skipped group and 3102.7 ± 273.8 grams in theskipped group at the early pregnancy and there were no significant differences. We are currently increasing
the case number and investigating nutritional situation during pregnancy. This study was approved by theinstitutional Ethics Committee.

29２３－１５
発表者：

大学院生 ■

大学院生以外 ☐タイトル (title)：Maternal nutritional status during pregnancy in Shimane Prefecture :Second report - Comparison among early, middle and late pregnancy –発表者 (presenters)：中谷陽子
所属 (affiliation)：：島根県立大学看護栄養学部
抄録 (abstract)【Background】 In Shimane prefecture, the birth rate of low birth weight infants is higher than thenational average, and the incidence of future non-communicable disease may increase.
【 Purpose 】 To investigate relationship between nutritional intake and birth weight of oﬀspring in
pregnant women in Shimane prefecture.
【Methods】In this study, we examined the food intake, We examined food intake, dietary and healthconsciousness in 26 pregnant women (average age, 29.8 ± 4.6 years) from 10 to 12 weeks (early), around
26 weeks (middle) and 36 weeks (late) of gestation. We then analyzed the relationship between nutrient
intake in each pregnancy period and birth weight.
【Results ＆Discussion】Among 26, 14 were primiparas (53.8%) and 12 were multiparas (46.2%).
Twenty-three (88.5%) had occupation, and three (11.5%) did not. Four (15.4%), 21 (80.8%), and one(3.8%) women had pre-pregnancy BMI in the "low body weight (≦18.5)" , "normal（18.5≦ ＜25.0）",
and"obese (25.0≦ ＜30.0)" range, respectively. The average hemoglobin values were 12.5 ± 0.6 g/dl,

and 11.2 ± 0.7 g/dl in early and late pregnancy, respectively. The average increase in body weight during
pregnancy was 10.4 ± 3.2 kg, and the average birth weight of the offspring was 3035.4±344.2 g. The
average birth weight of boys (15, 57.7%) and girls (11, 42.3%) was 3112.7 ± 346.1 g and 2929.9 ± 327.5
g, respectively. One (3.8%) was less than 2500 g. There was no correlation between the birth weight andpre-pregnancy BMI or weight gain during pregnancy. The amount of nutrient intake in most of thepregnant women in each pregnancy period is less than that recommended by the Ministry of Health, Laborand Welfare. Among 26, twenty-two (84.6%, early), 20 (76.9%, middle), and 16 (61.5%, late),
respectively, reported having stress and fatigue. The average birth weight tended to be heavier in the nonstressed group than in the stressed group. The total scores for dietary behavior and food consciousness
were not different at each pregnancy period. We are currently investigating the nutritional status at the
one-month checkup. This study was approved by the institutional Ethics Committee.

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