American Chemical Society (ACS) Acta Medica Okayama 0163-3864 2025 First Total Synthesis of the Kikai Island Polybrominated C3′–N1 Bisindole Alkaloid by a Directed Metalation Strategy EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The first total synthesis of one out of four Kikai Island polybrominated C3′–N1 bisindole alkaloids from red alga Laurencia brongniartii is described. The key steps involve both dehydration of trans-hemiaminal and a C2′-methylthiolation of bisindole using dimethyl disulfide through directed metalation, followed by C3-methylthiolation using a N-SMe succinimide reagent. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1359-7345 61 68 2025 Revisiting 3-azidoindoles: overcoming the trade-off challenges between stability and reactivity of in situ-generated azidoindoles 12801 12804 EN Shota Asai School of Pharmacy, Shujitsu University Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University A concise protocol based on the E2 reaction of indoline hemiaminals for accessing 3-azidoindoles is reported. In contrast to previous methods that require in situ generation by hypervalent iodine reagents, our protocol allows for the isolation of a variety of 3-azidoindoles upon a mild reaction for a short reaction time at room temperature. The obtained 3-azidoindoles are reasonably reactive, bench-stable and easy to handle. These findings could be used as a starting point for various reactions, including Huisgen reaction, [3+2] cycloaddition, phosphoramidation, and cine-substitution with the release of N2. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 12 5 2024 The Japan MSA registry: A multicenter cohort study of multiple system atrophy 271 277 EN Ayaka Chikada Department of Neurology, Graduate School of Medicine, The University of Tokyo Kenta Orimo Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Mitsui Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine and Dentistry Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Hidehiro Mizusawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Yuji Takahashi Department of Neurology, Graduate School of Medicine, The University of Tokyo Masahisa Katsuno Department of Neurology, Nagoya University Graduate School of Medicine Kazuhiro Hara Department of Neurology, Nagoya University Graduate School of Medicine Osamu Onodera Department of Neurology, Brain Research Institute, Niigata University Tomohiko Ishihara Department of Neurology, Brain Research Institute, Niigata University Masayoshi Tada Department of Neurology, Brain Research Institute, Niigata University Satoshi Kuwabara Department of Neurology, Graduate School of Medicine, Chiba University Atsuhiko Sugiyama Department of Neurology, Graduate School of Medicine, Chiba University Yoshitaka Yamanaka Department of Neurology, Graduate School of Medicine, Chiba University Ryosuke Takahashi Department of Neurology, Kyoto University Graduate School of Medicine Nobukatsu Sawamoto Department of Human Health Sciences, Kyoto University Graduate School of Medicine Yusuke Sakato Department of Neurology, Kyoto University Graduate School of Medicine Tomoyuki Ishimoto Department of Neurology, Kyoto University Graduate School of Medicine Ritsuko Hanajima Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University Yasuhiro Watanabe Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University Hiroshi Takigawa Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University Tadashi Adachi Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University Koji Abe Department of Neurology, Okayama University Graduate School of Medicine and Dentistry Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine and Dentistry Hiroshi Takashima Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University Keiko Higashi Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University Junichi Kira Department of Neurology, Graduate School of Medical Sciences, Kyushu University Ichiro Yabe Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Masaaki Matsushima Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Katsuhisa Ogata Department of Neurology, Higashi-Saitama National Hospital Kinya Ishikawa Department of Neurology and Neurological Science, Tokyo Medical and Dental University Yoichiro Nishida Department of Neurology and Neurological Science, Tokyo Medical and Dental University Taro Ishiguro Department of Neurology and Neurological Science, Tokyo Medical and Dental University Kokoro Ozaki Department of Neurology and Neurological Science, Tokyo Medical and Dental University Tetsuya Nagata Department of Neurology and Neurological Science, Tokyo Medical and Dental University Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Background: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and various motor symptoms. While MSA-C (cerebellar type) predominates in East Asia, MSA-P (parkinsonian type) predominates in Europe and North America. This nationwide patient registry aimed to (1) conduct a prospective natural history study of MSA in Japan, (2) facilitate patient recruitment for clinical trials, and (3) deposit bioresources and clinical information in a biobank.<br> Methods: Thirteen institutions participated in this study. Clinical information was obtained by neurologists from the patients visiting the hospital every 12 months to assess the UMSARS Part 2 scores and by telephone interviews by nurses every 6 months to assess UMSARS Part 1 scores and to determine whether clinical events had occurred.<br> Results: Demographic data from 329 MSA patients (216 MSA-C and 113 MSA-P) were analyzed. The mean age at symptom onset was 58.2 years (standard deviation, 8.9); the mean duration of symptoms at enrollment was 3.5 years (standard deviation, 2.2). The mean 12-month changes in the UMSARS Part 1 and Part 2 scores were 7.9 (standard deviation, 5.6) and 6.4 (standard deviation, 5.9), respectively. The patient registry proved useful in recruiting participants for clinical trials, including those with gene variants. Clinical information and biospecimens were deposited in a biobank.<br> Discussion: The study highlighted the importance of telephone interviews in minimizing drop-out rates in natural history studies and demonstrated similar MSA progression rates across populations. The deposited bioresources are available to researchers upon request, aiming to contribute to future MSA researches. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1359-7345 2025 Revisiting 3-azidoindoles: overcoming the trade-off challenges between stability and reactivity of in situ-generated azidoindoles EN Shota Asai School of Pharmacy, Shujitsu University Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University A concise protocol based on the E2 reaction of indoline hemiaminals for accessing 3-azidoindoles is reported. In contrast to previous methods that require in situ generation by hypervalent iodine reagents, our protocol allows for the isolation of a variety of 3-azidoindoles upon a mild reaction for a short reaction time at room temperature. The obtained 3-azidoindoles are reasonably reactive, bench-stable and easy to handle. These findings could be used as a starting point for various reactions, including Huisgen reaction, [3+2] cycloaddition, phosphoramidation, and cine-substitution with the release of N2. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 2025 One-pot synthesis of trans-2,3-diaminoindolines through 2,3-diamination of electrophilic indolines EN Yuito Kobori Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Despite recent advances in the synthesis of 2,3-diaminoindole derivatives, construction of 2,3-diaminoindolines, whose two amine moieties on each molecule differ from one another has yet to be achieved. In this work, we developed a concise one-pot protocol for differentiated diamination involving reacting a C2,C3-electrophilic indole reagent with amines to access a variety of previously inaccessible 2,3-diaminoindolines. Furthermore, the synthetic utility of this protocol was demonstrated by a successful gram-scale reaction and further transformation of the 2,3-diaminoindolines. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2193-5807 2025 2-Hydroxy-3-(Pyrrolidin-1-yl)-Indolines: A Platform for Accessing Decorated Deaminokynurenines Enabled by a Double Tautomeric Control e202500439 EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University In this study we introduce indoline hemiaminals as phenacyl bromide surrogates for the synthesis of deaminokynurenine derivatives through cyclic-linear tautomeric intermediates. The reaction proceeds through a tandem process involving the ring opening of indoline hemiaminals, generating transient acyclic aldehydes which are then trapped with in situ generated enolate species. Our protocol overcomes traditional dilemma in production of polar-mismatch 1,4-dicarbonyl compounds by utilizing a transient highly electrophilic linear aldehyde and late-stage transposition of carbonyl moiety. The synthetic utility of our transformation was demonstrated by follow-up transformations, including the first total synthesis of quinoline-2,4-dione alkaloid. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2624-8549 7 2 2025 Molecular Iodine-Catalyzed Synthesis of 3,3-Disubstituted Isatins: Total Synthesis of Indole Alkaloid, 3,3-Dimethoxy-2-oxindole 43 EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shota Asai School of Pharmacy, Shujitsu University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 3,3-Dialkoxy-2-oxindoles are prevalent in natural products and exhibit unique biological activities. Among them, acyclic alkoxy analogues show instability in acidic conditions, making access to acyclic isatin ketals highly challenging. Conventional methods for the synthesis of 3,3-dialkoxy-2-oxindoles usually require strongly acidic and harsh reaction conditions, resulting in a low overall efficiency. Herein, we report on an acid- and metal-free protocol for the synthesis of 3,3-dialkoxy-2-oxindoles from isatins through an iodine-catalyzed ketalization. This photochemical protocol does not require the use of any specific reagents such as metal catalysts. Furthermore, the total synthesis of an unprecedented 2-oxindole alkaloid bearing 3,3-dimethoxy moiety is achieved. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2193-5807 14 2 2024 Potassium tert-Butoxide-Mediated Ring-Opening of Indolines: Concise Synthesis of 2-Vinylanilines e202400552 EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shota Asai School of Pharmacy, Shujitsu University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University A concise and metal-free procedure has been developed for the synthesis of 2-vinylanilines. Reactions of indolines with tert-BuOK in DMSO afford the decorated 2-vinylanilines in yields up to 92 %. In addition, the 2, or 3-substituted indolines could be converted to trisubstituted alkenes. Also, the protocol can be scaled to afford gram quantities of the decorated 2-vinylanilines. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Antitumor activity of α-pinene in T-cell tumors EN Masaya ABE Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 22 36 2024 Indoline hemiaminals: a platform for accessing anthranilic acid derivatives through oxidative deformylation 7343 7348 EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuito Kobori Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shota Asai School of Pharmacy, Shujitsu University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 2-Aminobenzoyl chlorides possess both a nucleophilic nitrogen atom and an electrophilic carbonyl group, and thus selective acylation of nucleophiles is challenging; self-dimerization and sluggish reactions occur. Herein, we introduce a new synthetic protocol using 2-aminobenzoyl surrogates, allowing concise entry to decorated 2-aminobenzoyl derivatives in the absence of transition metals, acid chlorides, and specific reagents. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 14 1 2024 Suppression of PTBP1 in hippocampal astrocytes promotes neurogenesis and ameliorates recognition memory in mice with cerebral ischemia 20521 EN Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xinran Hu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The therapeutic potential of suppressing polypyrimidine tract-binding protein 1 (Ptbp1) messenger RNA by viral transduction in a post-stroke dementia mouse model has not yet been examined. In this study, 3 days after cerebral ischemia, we injected a viral vector cocktail containing adeno-associated virus (AAV)-pGFAP-mCherry and AAV-pGFAP-CasRx (control vector) or a cocktail of AAV-pGFAP-mCherry and AAV-pGFAP-CasRx-SgRNA-(Ptbp1) (1:5, 1.0 x 1011 viral genomes) into post-stroke mice via the tail vein. We observed new mCherry/NeuN double-positive neuron-like cells in the hippocampus 56 days after cerebral ischemia. A portion of mCherry/GFAP double-positive astrocyte-like glia could have been converted into new mCherry/NeuN double-positive neuron-like cells with morphological changes. The new neuronal cells integrated into the dentate gyrus and recognition memory was significantly ameliorated. These results demonstrated that the in vivo conversion of hippocampal astrocyte-like glia into functional new neurons by the suppression of Ptbp1 might be a therapeutic strategy for post-stroke dementia. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2624-8549 6 4 2024 Azidoindolines—From Synthesis to Application: A Review 556 580 EN Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Azide-containing compounds, organic azides, showcases a variety of reactivities, making them highly convenient and chameleonic intermediates. An indoline derivative has been proven to be of great significance in drug discovery due to its sp3-rich property. In this context, it is interesting to perform such vigorous azidation on medicinal-relevant indoles/indolines, resulting in the production of sp3-rich azidoindolines. The potential biological activity, in combination with the sp3-rich indoline bearing the azido moiety, makes azidoindolines an attractive synthetic target for medicinal and synthetic chemists. This review describes recent advances in the synthesis and application of azidoindolines: (1) iodine-mediated azidations, (2) metal-catalyzed azidations, (3) electrochemical azidations, (4) photochemical azidations, (5) azidation using a combination of an oxidant and an azide source, and (6) nucleophilic azidation. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0022-3263 89 14 2024 Formal One Carbon Deletion of Indoline Hemiaminals under Tautomeric Control to Access 2-Aminobenzyl Compounds 10349 10354 EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Unprecedented tert-BuOK-mediated one carbon deletion of indoline hemiaminals has been achieved. This novel protocol provides an efficient synthetic tool for the construction of 2-aminobenzyl compounds with high chemoselectivity. In addition, functionalized 2-aminobenzyl compounds are difficult to make, for which few limited means of access currently exist. The key to success is the use of in situ generated Heyns rearrangement products (α-amino carbonyl compounds) as precursors for formal one carbon deletion. No potential conflict of interest relevant to this article was reported.

IOS Press Acta Medica Okayama 1387-2877 100 1 2024 A Novel Peptidome Technology for the Diagnosis of Mild Cognitive Impairment and Alzheimer’s Disease by Selected Reaction Monitoring 219 228 EN Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koh Tadokoro Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Minaki Hamada Protosera, Inc. Kyoichi Asada Protosera, Inc. Lyang-Ja Lee Protosera, Inc. Hidehisa Tachiki Protosera, Inc. Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, National Center of Neurology and Psychiatry Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background:With the aging of populations worldwide, Alzheimer’s disease (AD) has become a concern due to its high prevalence and the continued lack of established treatments. Early diagnosis is required as a preventive intervention to modify the disease’s progression. In our previous study, we performed peptidomic analysis of serum samples obtained from AD patients and age-matched healthy subjects to seek peptide biomarker candidates for AD by using BLOTCHIP-MS analysis, and identified four peptides as AD biomarker candidates. <br> Objective:The objective was to validate the serum biomarker peptides to distinguish mild cognitive impairment (MCI) and AD in comparison to cognitively healthy controls using a new peptidome technology, the Dementia Risk Test. <br> Methods:We enrolled 195 subjects with normal cognitive function (NC; n = 70), MCI (n = 55), and AD (n = 70), The concentrations of cognitive impairment marker peptides (Fibrinogen α chain (FAC), Fibrinogen β chain (FBC), Plasma protease C1 inhibitor (PPC1I), α2-HS-glycoprotein (AHSG)) were quantified by using a selected reaction monitoring assay based on liquid chromatography-MS/MS. <br> Results:The present study confirmed that three peptides, FAC, FBC, and PPC1I, were significantly upregulated during the onset of AD. This three-peptide set was both highly sensitive in determining AD (sensitivity: 85.7%, specificity: 95.7%, AUC: 0.900) and useful in distinguishing MCI (sensitivity: 61.8%, specificity: 98.6%, AUC: 0.824) from NC. <br> Conclusions:In this validation study, we confirmed the high diagnostic potential of the three peptides identified in our previous study as candidate serum biomarkers for AD. The Dementia Risk Test may be a powerful tool for detecting AD-related pathological changes. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1359-7345 60 52 2024 Switchable synthesis of 3-aminoindolines and 2′-aminoarylacetic acids using Grignard reagents and 3-azido-2-hydroxyindolines 6615 6618 EN Toshiki Yamashiro Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The switchable synthesis of 3-aminoindolines and 2′-aminoaryl acetic acids from the same substrates, 3-azido-2-hydroxyindolines, was developed through denitrogenative electrophilic amination of Grignard reagents. The key to success is the serendipitous discovery that the reaction conditions, including solvents and reaction temperature, can affect the chemoselectivity. It is noteworthy that isotope-labeling experiments revealed the occurrence of the aziridine intermediate in the production of 2′-aminoaryl acetic acids. No potential conflict of interest relevant to this article was reported.

岡山大学文学部学芸員課程 Acta Medica Okayama 14 2020 学芸員課程 Newsletter 第14号 EN 10.18926/66818 No potential conflict of interest relevant to this article was reported.

岡山大学教師教育開発センター Acta Medica Okayama 2186-1323 14 2024 幼稚園における食物アレルギー教育に関する教員研修の実施とその評価　食物アレルギーの有無に関わらず，心身共に健康な生活を送る子供の育成をめざして 47 55 EN Yumiko SHINTAKU Kindergarten Attached to the School Education, Okayama University Fusako IYAMA Kindergarten Attached to the School Education, Okayama University Chiyo KUROSUMI Kindergarten Attached to the School Education, Okayama University Kouhei ABE Kindergarten Attached to the School Education, Okayama University Kayo KOTANI Kindergarten Attached to the School Education, Okayama University Mayumi TAKATORI Kindergarten Attached to the School Education, Okayama University Keita OKADA Kindergarten Attached to the School Education, Okayama University Maho TANAKA Kindergarten Attached to the School Education, Okayama University Saori MIKI Kindergarten Attached to the School Education, Okayama University 10.18926/CTED/66771 　本研究の目的は，幼稚園において食物アレルギーと共に生活する子供を育む方策を検討することである。本研究では，食物アレルギー教育に関する教員研修を行い，研修中の教員の反応と研修前後のアンケート調査の結果を基に，その効果を評価した。<br> 　研修後には,食物アレルギーやその対応によって生じる子供達の心境へも目を向ける必要性の理解が深まった。また事例検討を通して，幼稚園においても幼児なりに食物アレルギーを理解して対応できるように伝える必要性があると明らかになり，実際に指導できそうな具体的な場面も挙げられた。さらに研修中，脈々と受け継がれてきた“教育観”と，現在の多様化した時代背景や子供達の実態，社会的なつながりを踏まえて更新される“教育観”の中で揺れ動く教員の姿が見られ，その揺らぎや葛藤自体が，個別のニーズを適切に受け入れ，多様性を尊重する教師の観念を磨くことにつながっていると考えられた。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 185 2024 愛媛県と東京都における法令と手工科加設校の変遷との関連性（後編）― 愛媛県手工教育史（第五報） ― 53 71 EN Toshiyuki TAKAHASHI Faculty of Education, Okayama University 10.18926/bgeou/66707 　本論では，阿部七五三吉（1936）による「手工教育基礎建設の曙光時代」［1907（明治40）年頃～ 1926（大正15）年頃まで］の20 年間を調査対象期間として，小学校手工科関係の法令条文等を分析し，法令改正に則して『日本帝国文部省年報』を基に愛媛県の手工科加設校の数量的な変遷を東京都と比較検討することによって，愛媛県の尋常小学校と高等小学校における手工科の展開過程を探った。その結果，（1）法令条文等における尋常小学校と高等小学校の加設科目の取り扱い及び設置の条件と手工科加設校の増減には，強い関連性が見られ，特に「土地ノ情況」に影響を受けることが判明した。（2）高等小学校の加設科目に関する法令改正は，改正のない尋常小学校にも波及することが示唆された。（3）改善を期待して法令改正し文部大臣が訓令を発しても，必ずしも法令が目的とするようには，教育現場や教育界が反応しない場合もあることが明らかになった。 No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 22 9 2024 Synthetic strategies for the construction of C3–N1′ bisindoles 1756 1764 EN Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University C3–N1′ bisindoles are unique structures, and the construction of these structures has drawn much attention. However, their synthesis still presents significant challenges that limit the functional group compatibility. This minireview summarizes the recent progress in the methodology for constructing C3–N1′ bisindoles. There are two approaches for access to C3–N1′ bisindoles: (1) direct approaches including reverse polarity techniques. (2) Stepwise approaches using designed and prefunctionalized substrates enable further functionalization by additional reactions to facilitate access to the target products. I believe that this review will allow its readers to develop novel approaches for the synthesis of C3–N1′ bisindoles. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0947-6539 30 11 2024 On Demand Synthesis of C3−N1’ Bisindoles by a Formal Umpolung Strategy: First Total Synthesis of (±)‐Rivularin A e202302963 EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University In this work, a straightforward synthesis of C3−N1’ bisindolines is achieved by a formal umpolung strategy. The protocols were tolerant of a wide variety of substituents on the indole and indoline ring. In addition, the C3−N1’ bisindolines could be converted to C3−N1’ indole-indolines and C3−N1’-bisindoles. Also, we have successfully synthesized (±)-rivularin A through a biomimetic late-stage tribromination as a key step. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2624-8549 5 4 2023 Total Synthesis of the Proposed Structure of Indolyl 1,2-Propanediol Alkaloid, 1-(1H-Indol-3-yloxy)propan-2-ol 2772 2784 EN Momoko Kimata Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The first total synthesis of the proposed structure of unprecedented indolyl derivative bearing 1,2-propanediol moiety is described. Isomerization of 3-alkoxyindolines through indolenium intermediates was the key step in the total synthesis. H-1, C-13-NMR, IR, and HRMS spectra of the synthetic compound drastically differed to those of the originally reported structure, which suggests the natural product requires revision. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1434-193X 27 4 2023 Concise Synthesis of Thiazolo[4,5-b]indoles via Ring Switch/Cyclization Sequences e202301130 EN Koji Yamada Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Tetsu Tsubogo Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Hikaru Kanazawa Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Sayaka Ishizuka Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Koutaro Ohyama Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Masaki Kaida Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The unexpected reactions of indoline hemiaminals affords 2,5-diaryl-4-hydroxythiazolines through a thioamidation/ring switch sequence. The key to success of this transformation is to use a thioamide as a thiazoline precursor under transient tautomeric control. This transformation features mild reaction conditions and good yields with broad functional group tolerance (17 examples, up to 99 % yield). Further transformations of the thiazolines provide a direct entry to dihydrothiazolo[4,5-b]indoles and thiazolo[4,5-b]indoles. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 0963-6897 32 2023 Safety and Clinical Effects of a Muse Cell-Based Product in Patients With Amyotrophic Lateral Sclerosis: Results of a Phase 2 Clinical Trial EN Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yumiko Nakano Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Sasaki Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koh Tadokoro Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshio Omote Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taijun Yunoki Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Kawahara Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Namiko Matsumoto Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Taira Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chika Matsuoka Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuta Morihara Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Abe Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of motor neurons. Multilineage-differentiating stress-enduring (Muse) cells are unique endogenous stem cells that show therapeutic effects on motor function in ALS mouse models. We conducted a single-center open phase II clinical trial to evaluate the safety and clinical effects of repeated intravenous injections of an allogenic Muse cell-based product, CL2020, in patients with ALS. Five patients with ALS received CL2020 intravenously once a month for a total of six doses. The primary endpoints were safety and tolerability, and the secondary endpoint was the rate of change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score. In addition, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), sphingosine-1-phosphate (S1P), cerebrospinal fluid chitotriosidase-1 (CHIT-1), and neurofilament light chain (NfL) levels were evaluated. The CL2020 treatment was highly tolerated without serious side effects. The ALSFRS-R score change trended upward at 12 months post-CL2020 treatment compared with that at 3 months pre-administration, but the difference was not statistically significant. Among five patients diagnosed with ALS, three exhibited a decrease in the rate of ALSFRS-R score change, one demonstrated an increase, and another showed no change. In addition, the patients’ serum IL-6 and TNF-α levels and cerebrospinal fluid CHIT-1 and NfL levels increased for up to 6 months post-treatment; however, their serum S1P levels continuously decreased over 12 months. These findings indicate a favorable safety profile of CL2020 therapy. In the near future, a double-blind study of a larger number of ALS patients should be conducted to confirm the efficacy of ALS treatment with CL2020. No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 183 2023 手工教育基礎建設の曙光時代における愛媛教育協会機関誌に 見られる手工教育の実態（後編） ― 愛媛県手工教育史（第四報） ― 15 27 EN Toshiyuki TAKAHASHI Faculty of Education, Okayama University 10.18926/bgeou/65922 　本論は，阿部七五三吉（1936）による「手工教育基礎建設の曙光時代」［1907（明治40 年）頃～ 1926（大正15）年頃まで］における，1911（明治44）年の「改正小学校令」から1926（大正15）年の「改正小学校令」までの14 年９か月間を調査対象期間として，愛媛教育協会機関誌に見られる手工教育関係史料を調査し，愛媛県の尋常小学校及び高等小学校における手工科の成立及び展開過程を探った。その結果，1911（明治44）年の「改正小学校令」によって手工科は，高等小学校実業科目の選択必修科目の一つとなったが，実業科目としての性格が強くなると同時に，授業時数の増加が小学校にとって負担になり，手工科加設校は結果的に減少し，愛媛県の小学校における手工教育は混迷した。 No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0022-3263 88 14 2023 Oxytrofalcatin Puzzle: Total Synthesis and Structural Revision of Oxytrofalcatins B and C 9920 9926 EN Kazuma Sugitate Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiki Yamashiro Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ibuki Takahashi Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-tobetsu, Hokkaido 0610293, Japan Koji Yamada Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The previously reported structures of oxytrofalcatins B and C possess a benzoyl indole core. However, following synthesis and NMR comparison of both the proposed structure and the synthesized oxazole, we have revised the structure of oxytrofalcatins B and C as oxazoles. The synthetic route developed herein can further our understanding of the biosynthetic pathways that govern the production of natural 2,5-diaryloxazoles. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0022-510X 447 2023 Neuroprotective effects of carnosine in a mice stroke model concerning oxidative stress and inflammatory response 120608 EN Xinran Hu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tian Feng Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Zhihong Bian Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haibo Yu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xiao Hu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuting Bian Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hongming Sun Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Carnosine (β-alanyl-L-histidine) is a natural dipeptide with multiple neuroprotective properties. Previous studies have advertised that carnosine scavenges free radicals and displays anti-inflammatory activity. However, the underlying mechanism and the efficacies of its pleiotropic effect on prevention remained obscure. In this study, we aimed to investigate the anti-oxidative, anti-inflammative, and anti-pyroptotic effects of carnosine in the transient middle cerebral artery occlusion (tMCAO) mouse model. After a daily pre-treatment of saline or carnosine (1000 mg / kg / day) for 14 days, mice (n = 24) were subjected to tMCAO for 60 min and continuously treated with saline or carnosine for additional 1 and 5 days after reperfusion. The administration of carnosine significantly decreased infarct volume 5 days after the tMCAO (*p < 0.05) and effectively suppressed the expression of 4-HNE, 8-OHdG, Nitrotyrosine 5 days, and RAGE 5 days after tMCAO. Moreover, the expression of IL-1β was also significantly suppressed 5 days after tMCAO. Our present findings demonstrated that carnosine effectively relieves oxidative stress caused by ischemic stroke and significantly attenuates neuroinflammatory responses related to IL-1β, suggesting that carnosine can be a promising therapeutic strategy for ischemic stroke. No potential conflict of interest relevant to this article was reported.

CUREUS INC Acta Medica Okayama 2168-8184 15 3 2023 A Case of Drug-Resistant Myoclonus Improved by Only Slight Adjustment to the Hemodialysis Setting e36104 EN Ryo Sasaki Department of Neurology, Okayama University Chika Matsuoka Department of Neurology, Hiroshima City Hiroshima Citizens Hospital Toru Yamashita Department of Neurology, Okayama University Masaru Kinomura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Koji Abe Department of Neurology, National Center of Neurology and Psychiatry Myoclonus, a rare complication in patients with end-stage renal disease, is typically ameliorated through hemodialysis. The present case concerns an 84-year-old male with chronic renal failure undergoing hemodialysis, presenting involuntary movements in his limbs, which gradually worsened from the initiation of hemodialysis without constant elevation of serum blood urea nitrogen and electrolytes levels. Surface electromyography revealed characteristic findings consistent with myoclonus. He was diagnosed with subcortical-nonsegmental myoclonus related to hemodialysis, and the myoclonus was significantly alleviated after slightly increasing the post-dialysis target weight even though drug treatment was ineffective. This case suggests that drug-resistant myoclonus in patients with renal failure may be improved by adjusting hemodialysis settings, even in cases of atypical dialysis disequilibrium syndrome. No potential conflict of interest relevant to this article was reported.

The Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 62 3 2023 Actual Telemedicine Needs of Japanese Patients with Neurological Disorders in the COVID-19 Pandemic 365 371 EN Ryo Sasaki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective During the coronavirus disease 2019 (COVID-19) pandemic, many social activities have moved online using applications for digital devices (e.g. computers, smartphones). We investigated the needs of telemedicine and trends in medical status and social care situations of Japanese patients with neurological disorders in order to estimate their affinity for an online telemedicine application. Methods We designed an original questionnaire for the present study that asked participants what problems they had with hospital visits, how the COVID-19 pandemic had affected their lives, and whether or not they would like to receive telemedicine.Patients The present study included volunteer caregivers, participants with Parkinson's disease (PD), epiamyotrophic lateral sclerosis (ALS), headache, myopathy, and other neurological diseases from Okayama University Hospital. Results A total of 29.6% of patients wanted to use telemedicine. Patients with ultheadaches (60.0%) and epilepsy (38.1%) were more likely to want to use telemedicine than patients with PD (17.8%) or stroke (19.0%). Almost 90% of patients had access to a digital device, and there was no association between favoring telemedicine, ownership of a digital device, hospital visiting time, or waiting time at the hospital, although age was associated with motivation to telemedicine use (52.6 vs. 62.2 years old, p < 0.001). Conclusion We can contribute to the management of the COVID-19 pandemic and the medical economy by promoting telemedicine, especially for young patients with headaches or epilepsy. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 24 5 2023 Revisiting Cryptocyanine Dye, NK-4, as an Old and New Drug: Review and Future Perspectives 4411 EN Shihui Liu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University NK-4 plays a key role in the treatment of various diseases, such as in hay fever to expect anti-allergic effects, in bacterial infections and gum abscesses to expect anti-inflammatory effects, in scratches, cuts, and mouth sores from bites inside the mouth for enhanced wound healing, in herpes simplex virus (HSV)-1 infections for antiviral effects, and in peripheral nerve disease that causes tingling pain and numbness in hands and feet, while NK-4 is used also to expect antioxidative and neuroprotective effects. We review all therapeutic directions for the cyanine dye NK-4, as well as the pharmacological mechanism of NK-4 in animal models of related diseases. Currently, NK-4, which is sold as an over-the-counter drug in drugstores, is approved for treating allergic diseases, loss of appetite, sleepiness, anemia, peripheral neuropathy, acute suppurative diseases, wounds, heat injuries, frostbite, and tinea pedis in Japan. The therapeutic effects of NK-4’s antioxidant and neuroprotective properties in animal models are now under development, and we hope to apply these pharmacological effects of NK-4 to the treatment of more diseases. All experimental data suggest that different kinds of utility of NK-4 in the treatment of diseases can be developed based on the various pharmacological properties of NK-4. It is expected that NK-4 could be developed in more therapeutic strategies to treat many types of diseases, such as neurodegenerative and retinal degenerative diseases. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0163-3864 85 8 2022 First Total Synthesis of Reassigned Echinosulfonic Acid D 2122 2125 EN Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ren Nakajima Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiki Yamashiro Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Sawada Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Echinosulfonic acid D, a sponge metabolite whose structure was recently reassigned, was synthesized for the first time. The key step is the double indolization of dimethylbarbituric acid using the umpolung indole reagent, followed by a hydrolysis/decarboxylation/esterification sequence. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 10 5 2022 A Japanese case of successful surgical resection of cerebral cavernous malformations with a CCM2 mutation 255 258 EN Emi Nomura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshio Omote Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuya Sasaki Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Akagawa Tokyo Women's Medical University Institute for Integrated Medical Sciences Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Cerebral cavernous malformations (CCMs) are congenital abnormalities of cerebral vessels. Surgical resection is rarely considered for the control of epilepsy in a first seizure patient with vascular malformation. In contrast, lesions that produce repetitive or progressive symptoms should be considered for surgical resection as treatment. Herein, we report a Japanese patient with a CCM2 mutation, c.609G>A (p.K203K) substitution, who showed drug-resistant epilepsy and dramatic improvement after surgical resection. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Evaluation of Patient Positioning During Digital Tomosynthesis and ReconstructionAlgorithms for Ilizarov Frames: A Phantom Study EN Yuki Abe Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0947-6539 28 37 2022 Indole Editing Enabled by HFIP‐Mediated Ring‐Switch Reactions of 3‐Amino‐2‐Hydroxyindolines e202201113 EN Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiki Yamashiro Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaho Shimizu Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Sawada Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We found the novel reactivity of hemiaminal as a precursor for indole editing at the multi-site. The HFIP-promoted indole editing of indoline hemiaminals affords 2-arylindoles through a ring-switch sequence. The key to success of this transformation is to use a cyclic hemiaminal as an a-amino aldehyde surrogate under transient tautomeric control. This transformation features mild reaction conditions and good yields with broad functional group tolerance. The utility of this transformation is presented through the one-pot protocol and the synthesis of isocryptolepine. No potential conflict of interest relevant to this article was reported.

IOS Press Acta Medica Okayama 1387-2877 86 1 2022 Protective Effect of Rivaroxaban Against Amyloid Pathology and Neuroinflammation Through Inhibiting PAR-1 and PAR-2 in Alzheimer’s Disease Mice 111 123 EN Zhihong Bian Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xia Liu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tian Feng Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haibo Yu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xiao Hu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xinran Hu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuting Bian Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hongming Sun Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koh Tadokoro Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe National Center Hospital, National Center of Neurology and Psychiatry Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Recent studies have revealed that atrial fibrillation (AF) patients have a high risk of developing cognitive impairment, vascular dementia, and Alzheimer’s disease (AD). Some reports suggest that the application of oral anticoagulant with an appropriate dose may have a preventive effect on AD. However, which oral anticoagulant drug is more appropriate for preventing AD and the underlying mechanism(s) is still unknown. Objective: The aim of the present study was to assess the treatment effect of rivaroxaban administration as well as investigate the roles of PAR-1 and PAR-2 in the AD + CAA mice model. Methods: In the present study, we compared a traditional oral anticoagulant, warfarin, and a direct oral anticoagulant (DOAC), rivaroxaban, via long-term administration to an AD with cerebral amyloid angiopathy (CAA) mice model. Results: Rivaroxaban treatment attenuated neuroinflammation, blood-brain barrier dysfunction, memory deficits, and amyloid-β deposition through PAR-1/PAR-2 inhibition in the AD + CAA mice model compared with warfarin and no-treatment groups. Conclusion: The present study demonstrates that rivaroxaban can attenuate AD progress and can be a potential choice to prevent AD. No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科考古学研究室 Acta Medica Okayama 2022 飯盛山東1号墳 －墳丘測量調査・石棺発掘調査報告－ EN Akira Seike The Department of Archaeology, Okayama University 本書は、岡山市北区芳賀3082番1に所在する飯盛山東1号墳において、2019年3月に行われた墳丘測量調査と石棺の発掘調査報告である。本古墳は周知の埋蔵文化財包蔵地として登録されていたが、名称を持たなかったため、調査に当たり岡山市と協議の上、飯盛山東1号墳の名称を与えた。本調査は、岡山大学考古学研究室が主体となり、清家章（岡山大学大学院社会文化科学研究科教授）が担当して調査を実施した。 No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0022-510X 387 15 2018 Familial and sporadic chronic progressive degenerative parietal ataxia 70 74 EN Ryuta Morihara Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Toru Yamashita Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Kentaro Deguchi Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Tomoko Kurata Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Emi Nomura Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Kota Sato Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Yumiko Nakano Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Yasuyuki Ohta Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Nozomi Hishikawa Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Takeshi Ikeuchi Department of Molecular Genetics, Bioresource Science Branch, Center of Bioresource, Brain Research Institute Niigata University Masataka Kitaguchi Department of Neurology, Baba Memorial Hospital Koji Abe Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Background & objective: Parietal ataxia has been mainly reported as a consequence of acute ischemic stroke, while degenerative parietal ataxia has not been reported. Methods: We investigated clinical characteristics, neuroimaging data, and genetic analysis of patients with cerebellar ataxia plus parietal atrophy. Results: We identified seven patients, including five patients from two families, with chronic progressive cerebellar ataxia due to degenerative parietal atrophy but not stroke. Age at onset of ataxia was 57.6 +/- 6.9 years. All patients showed chronic progressive cerebellar ataxia with severity of ataxic gait > limb ataxia > dysarthria. Patients showed no cognitive dysfunction, muscle weakness, or parkinsonism, and only two patients showed mild sensory disturbances. The seven patients showed lateralized limb ataxia with greater contralateral parietal lobe atrophy by magnetic resonance imaging, and hypoperfusion by single photon emission computed tomography, without any abnormal cerebellar pathology (i.e., crossed cerebellar diaschisis). Pathogenic mutations in the microtubule-associated protein tau gene were not found using two single nucleotide polymorphisms. Conclusions: This is the first description showing unique clinical features of familial and sporadic chronic progressive degenerative parietal ataxia. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0360-4012 95 9 2016 Reduction of intracerebral hemorrhage by rivaroxaban after tPA thrombolysis is associated with downregulation of PAR-1 and PAR-2 1818 1828 EN Ryuta Morihara Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Toru Yamashita Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Syoichiro Kono Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Jingwei Shang Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Yumiko Nakano Departments of Neurology Kota Sato Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Nozomi Hishikawa Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Yasuyuki Ohta Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Stefan Heitmeier Bayer Pharma AG, Drug Discovery - Global Therapeutic Research Groups, Cardiovascular Pharmacology Elisabeth Perzborn Bayer Pharma AG, Drug Discovery - Global Therapeutic Research Groups, Cardiovascular Pharmacology Koji Abe Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University This study aimed to assess the risk of intracerebral hemorrhage (ICH) after tissue-type plasminogen activator (tPA) treatment in rivaroxaban compared with warfarin-pretreated male Wistar rat brain after ischemia in relation to activation profiles of protease-activated receptor-1, -2, -3, and -4 (PAR-1, -2, -3, and -4). After pretreatment with warfarin (0.2 mg/kg/day), low-dose rivaroxaban (60 mg/kg/day), high-dose rivaroxaban (120 mg/kg/day), or vehicle for 14 days, transient middle cerebral artery occlusion was induced for 90 min, followed by reperfusion with tPA (10 mg/kg/10 ml). Infarct volume, hemorrhagic volume, immunoglobulin G leakage, and blood parameters were examined. Twenty-four hours after reperfusion, immunohistochemistry for PARs was performed in brain sections. ICH volume was increased in the warfarin-pretreated group compared with the rivaroxaban-treated group. PAR-1, -2, -3, and -4 were widely expressed in the normal brain, and their levels were increased in the ischemic brain, especially in the peri-ischemic lesion. Warfarin pretreatment enhanced the expression of PAR-1 and PAR-2 in the peri-ischemic lesion, whereas rivaroxaban pretreatment did not. The present study shows a lower risk of brain hemorrhage in rivaroxaban-pretreated compared with warfarin-pretreated rats following tPA administration to the ischemic brain. It is suggested that the relative downregulation of PAR-1 and PAR-2 by rivaroxaban compared with warfarin pretreatment might be partly involved in the mechanism of reduced hemorrhagic complications in patients receiving rivaroxaban in clinical trials. © 2016 Wiley Periodicals, Inc. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 0271-678X 2022 Efficacy and safety of spot heating and ultrasound irradiation on in vitro and in vivo thrombolysis models EN Ryuta Morihara Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Osakada Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tian Feng Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Xinran Hu Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Fukui Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan Koh Tadokoro Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Takemoto Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Abe Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences <jats:p> The feasibility of transcranial sonothrombolysis has been demonstrated, although little is known about the relationships between thermal or mechanical mechanisms and thrombolytic outcomes. Therefore, the present study aims to reveal the effect and safety of temperature and ultrasound through in vitro and in vivo thrombolysis models. Artificial clots in microtubes were heated in a water bath or sonicated by ultrasound irradiation, and then clots weight decrease with rising temperature and sonication time was confirmed. In the in vitro thrombotic occlusion model, based on spot heating, clot volume was reduced and clots moved to the distal side, followed by recanalization of the occlusion. In the in vivo study, the common carotid artery of rats was exposed to a spot heater or to sonication. No brain infarct or brain blood barrier disruption was shown, but endothelial junctional dysintegrity and an inflammatory response in the carotid artery were detected. The present spot heating and ultrasound irradiation models seem to be effective for disintegrating clots in vitro, but the safety of the in vivo model was not fully supported by the data. However, the data indicates that a shorter time exposure could be less invasive than a longer exposure. </jats:p> No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 56 17 2017 Successful Delayed Aortic Surgery for a Patient with Ischemic Stroke Secondary to Aortic Dissection 2343 2346 EN Ryuta Morihara Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Toru Yamashita Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Kentaro Deguchi Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan Keiichiro Tsunoda Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan Yasuhiro Manabe Department of Neurology, Okayama National Hospital Medical Center, Japan Yoshiaki Takahashi Department of Neurology, Okayama National Hospital Medical Center, Japan Taijun Yunoki Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan Kota Sato Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan Yumiko Nakano Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan Syoichiro Kono Department of Neurology, Okayama National Hospital Medical Center, Japan Yasuyuki Ohta Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan Nozomi Hishikawa Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan Koji Abe Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan The diagnosis of aortic dissection (AD) is sometimes difficult within the limited time window of recombinant tissue plasminogen activator (tPA) for ischemic stroke (IS). A 60-year-old man developed sudden left hemiparesis due to IS. During tPA infusion, his blood pressure dropped and consciousness declined. After transfer to our hospital, carotid duplex ultrasonography led to a diagnosis of AD. Emergency surgery was postponed because of the risk of hemorrhagic transformation. The patient successfully underwent aortic surgery on day 5 and was discharged with a remarkable improvement in his symptoms. Delayed surgery may avoid hemorrhagic transformation in patients with AD-induced IS who have received tPA. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 2052-4129 9 7 2022 Synthesis of 2-monosubstituted indolin-3-ones by cine-substitution of 3-azido-2-methoxyindolines 1897 1903 EN Toshiki Yamashiro Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Sawada Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We report herein a formal cine-substitution/hydrolysis of 3-azidoindoles generated from 3-azido-2-methoxyindolines (AZINs). This protocol enables the introduction of various carboxylic acids and alcohols into indolin-3-ones at the C2-position, affording 2-monoacyloxy or alkoxy indolin-3-ones. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 10 2022 A case of a heterozygous ABCC6 mutation showing recurrent ischemic strokes and intracranial hemorrhages 98 101 EN Emi Nomura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuko Kawahara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshio Omote Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Takahashi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Namiko Matsumoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Ikegami Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Uemura Department of Neurology, Brain Research Institute, Niigata University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mutations in the ATP-binding cassette subfamily C member 6 (ABCC6) gene are responsible for pseudoxanthoma elasticum (PXE). PXE is a rare genetic metabolic disease with autosomal recessive inheritance that shows ectopic mineralization in skin, eyes and blood vessels, and causes cerebrovascular disease. There are few reports of intracranial hemorrhages in patients with the ABCC6 mutation. We report the first Japanese case with a heterozygous ABCC6 mutation displaying recurrent ischemic strokes and intracranial hemorrhages. We propose that the ABCC6 mutation may be one cause of neurovascular diseases with a family history. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1359-7345 57 2021 cis-3-Azido-2-methoxyindolines as safe and stable precursors to overcome the instability of fleeting 3-azidoindoles 13381 13384 EN Toshiki Yamashiro Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaru Tanioka School of Pharmaceutical Sciences, Aichi Gakuin University Shinichiro Kamino School of Pharmaceutical Sciences, Aichi Gakuin University Daisuke Sawada Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Use of 3-azidoindoles in organic synthesis remains a difficult task owing to their instabilities. Herein, we report a general and concise approach for tackling this problem by using 3-azidoindole surrogates. The surrogates are bench-stable, presumably due to the observed intramolecular O-N-beta bonding. The resultant fleeting intermediates undergo capturing in situ to afford 3-substitued indoles through formal ipso-substitution of the azide group by nucleophiles. In these investigations, we found that the fleeting 3-azidoindoles show a C3-electrophilic character for the first time. No potential conflict of interest relevant to this article was reported.

The Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 60 19 2021 Nodal Peripheral T-cell Lymphoma with T Follicular Helper Phenotype Presenting as Chorea During Treatment: A Case Report and Literature Review 3155 3160 EN Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Ryoya Yukawa Department of Hematology and Oncology, Okayama University Hospital Ryo Sasaki Department of Neurology, Okayama University Hospital Chikamasa Yoshida Department of Hematology, Okayama City Hospital Hiroki Takasuka Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Division of Clinical Laboratory, Okayama University Hospital Nobuharu Fujii Division of Blood Transfusion, Okayama University Hospital Ken-Ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Koji Abe Department of Neurology, Okayama University Hospital Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital A 72-year-old man presented with chorea while undergoing treatment for recurrence of nodal peripheral T-cell lymphoma with T follicular helper (TFH) phenotype. An examination by brain N-isopropyl-p-iodoamphetamine (I-123-IMP)-single photon emission computed tomography (SPECT) revealed no abnormalities other than a decreased cerebral blood flow (CBF) in the left striatum. After four courses of salvage chemotherapy, his clinical symptoms and asymmetric cerebral perfusion improved, suggesting that the decreased CBF had caused chorea. The significance of brain SPECT has not been fully clarified in patients with chorea-associated malignant lymphoma, warranting further investigations. Brain SPECT is an alternative approach to identify abnormalities in such patients. No potential conflict of interest relevant to this article was reported.

The Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 60 13 2021 A Unique Case of Encephalopathy with an Elevated IgG-4 and Extremely High Interleukin-6 Level and Delayed Myelodysplastic Syndrome 2125 2128 EN Namiko Matsumoto Departments of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Departments of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Ikegami Departments of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Departments of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshio Omote Departments of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Departments of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tom Yamashita Departments of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Taniguchi Departments of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Departments of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We herein report a 75-year-old man who developed disturbed consciousness with polynuclear cell dominant pleocytosis and low glucose and extremely high interleukin (IL)-6 levels in his cerebrospinal fluid. The biopsy specimen from his right supraclavicular lymph node showed the infiltration of inflammatory cells positive for IgG, IgG4 and IL-6. Prednisolone and azathioprine administered under suspicion of IgG4-related disease (IgG4-RD) or multicentric Castleman's disease (MCD) successfully remitted the symptoms. However, he developed myelodysplastic syndrome (MDS) and died 18 months later. The extremely high IL-6 may have been related to the rare neurological manifestations and development of MDS in the present case. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 58 21 2019 Spastic Paraplegia Accompanied by Extrapyramidal Sign and Frontal Cognitive Dysfunction 3163 3165 EN Ryo Sasaki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koh Tadokoro Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Takahashi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Ishiura Department of Neurology, The University of Tokyo Hospital Shoji Tsuji Department of Molecular Neurology, The University of Tokyo Hospital, Japan Institute of Medical Genomics, International University of Health and Welfare Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University A complicated form of spastic paraplegia is a neurodegenerative disorder presenting as progressive spasticity in the bilateral lower limbs accompanied by some clinical features. The present case showed spastic paralysis and hyperreflexia in all extremities as well as lead pipe rigidity in the neck and bilateral upper extremities (R < L), decreased scores on frontal cognitive tests, a decreased accumulation of the right dorsal putamen on a DAT scan, and hypoperfusion of the bilateral frontal lobes on 99mTc-ECD single photon emission computed tomography (SPECT). The present case provides a new spectrum of spastic paraplegia based on the evidence of clinical scores and the findings of brain functional imaging. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 58 7 2019 Characteristic Clinical Features of Werner Syndrome with a Novel Compound Heterozygous WRN Mutation c.1720+1G>A Plus c.3139-1G>C 1033 1036 EN Namiko Matsumoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaro Deguchi Department of Neurology, Okayama Citizen's Hospital Masayuki Kishida Department of General Internal Medicine, Okayama Citizen's Hospital Kota Sato Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aki Watanabe Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University Koutaro Yokote Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University Minoru Takemoto Department of Diabetes, Metabolism and Endocrinology, School of Medicine, International University of Health and Welfare Junko Oshima Department of Pathology, University of Washington Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Werner syndrome (WS) is an autosomal recessive progeroid disorder caused by mutations in the WRN gene (WRN). Most Japanese WS patients are born from a consanguineous marriage with homozygous WRN mutations. We herein report a rare WS patient born from non-consanguineous parents with compound heterozygous WRN mutations with a novel heterogeneous c.1720+1G>A substitution plus the most frequent heterogeneous c.3139-1G>C substitution among Japanese. Although the present case showed clinical characteristics common to previous Japanese WS patients, he had not developed any malignant tumors as of 43 years of age, suggesting that WS patients with this particular genetic mutation have a different phenotype than others. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 58 3 2019 A Rare Case of Klinefelter Syndrome Accompanied by Spastic Paraplegia and Peripheral Neuropathy 437 440 EN Ryo Sasaki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Takahashi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Tsunoda Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koh Tadokoro Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Klinefelter syndrome is a chromosomal disorder with a typical karyotype of 47, XXY, accompanied by various neurological symptoms. We herein report the first case of Klinefelter syndrome with a rare mosaic form of 47, XXY and 48, XXXY, combined with both spastic paraplegia and peripheral motor neuropathy. This case showed spasticity and hyperreflexia with pathological reflexes and ankle clonus as well as muscle weakness in all extremities. A motor nerve conduction study and the magnetic motor evoked potential suggested motor axonal neuropathy and corticospinal tract disorders. The present case suggests that Klinefelter syndrome can present with both upper and lower motor neuron degeneration. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 58 8 2019 Improving Anxiety in Subacute Myelo-optico-neuropathy (SMON) after an Automated Telephone Call Service 1081 1085 EN Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinji Doutare Doutare Medical Clinic Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective We evaluated the clinical effects of a telephone call service for psychological symptoms such as anxiety, depression or apathy in subacute myelo-optico-neuropathy (SMON) patients living alone or with a single caregiver. </br> Methods Up to 16 SMON patients (4 men, 12 women) and 32 control subjects were evaluated by the geriatric depression scale (GDS), apathy scale (AS) and state and trait anxiety inventory (STAI) forms X-I, including the P and A values for depression, apathy and state anxiety including disturbed peace of mind and enhanced anxiety, respectively, before (pre) and three months after (post) the telephone call service. </br> Results The SMON patients, especially women, had significantly worse baseline scores in GDS (depression), AS (apathy) and STAI (state anxiety) than control subjects. The automated telephone call service significantly improved the high baseline STAI scores, including the P and A scores (disturbed peace of mind and enhanced anxiety), of SMON patients but not the GDS or AS scores. </br> Conclusion SMON patients, especially women, living alone or with a single caregiver showed higher baseline depression, apathy and anxiety scores than the control subjects. The present automated telephone call service proved to be a useful care tool for improving the anxiety of SMON patients with high STAI P and A scores. No potential conflict of interest relevant to this article was reported.

The Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 60 2 2021 The Oldest Japanese Case of Combined Central and Peripheral Demyelination, which Developed Nine Years After the First Instance of Optic Neuritis 305 308 EN Emi Nomura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuko Kawahara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshio Omote Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koh Tadokoro Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidenori Ogata Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Combined central and peripheral demyelination (CCPD) causes demyelination in both the central and peripheral nervous systems. Anti-neurofascin 155 antibody plays an important pathogenic role in CCPD, but evidence concerning an association between this antibody and CCPD remains inconclusive. Although there have been no reports of precedent optic neuritis developing into CCPD, we herein report a Japanese man in whom optic neuritis recurred four times over nine years and who developed CCPD without positive antineurofascin 155 antibody. This case suggests the possibility of developing CCPD after optic nerve neuritis and the existence of an unknown antibody that induces CCPD. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1477-7827 19 1 2021 Effect of edaravone on pregnant mice and their developing fetuses subjected to placental ischemia 19 EN Marwa Atallah Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Abe Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Growing evidence indicates that reduced uterine perfusion pressure (RUPP) triggers the cascade of events leading to preeclampsia. Edaravone is a powerful free radical scavenger used for the treatment of ischemia/reperfusion diseases due to its anti-oxidative stress and anti-inflammatory properties. Here we investigate the effect of edaravone (3 mg/kg) on different maternal and fetal outcomes of RUPP-induced placental ischemia mice model. RUPP surgery was performed on gestation day (GD) 13 followed by edaravone injection from GD14 to GD18, sacrifice day. The results showed that edaravone injection significantly decreased the maternal blood pressure (113.2 +/- 2.3 mmHg) compared with RUPP group (131.5 +/- 1.9 mmHg). Edaravone increased fetal survival rate (75.4%) compared with RUPP group (54.4%), increased fetal length, weights, and feto-placental ratio (7.2 and 5.7 for RUPP and RUPP-Edaravone groups, respectively) compared with RUPP group. In addition, RUPP resulted in many fetal morphological abnormalities as well as severe delayed ossification, however edaravone decreased the morphological abnormalities and increased the ossification of the fetal endoskeleton. Edaravone improved the histopathological structure of the maternal kidney and heart as well as decreased the elevated blood urea and creatinine levels (31.5 +/- 0.15 mg/dl (RUPP), 25.6 +/- 0.1 mg/dl (RUPP+edaravone) for urea and 5.4 +/- 0.1 mg/dl (RUPP), 3.5 +/- 0.1 mg/dl (RUPP+edaravone) for creatinine) and decreased cleaved caspase-3 expression in the maternal kidney. In conclusion, this study demonstrated that our RUPP mice model recapitulated preeclampsia symptoms and edaravone injection ameliorated most of these abnormalities suggesting its effectiveness and potential application in preeclampsia treatment regimes. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0167-6393 126 2021 Model architectures to extrapolate emotional expressions in DNN-based text-to-speech 35 43 EN Katsuki Inoue Graduate school of Interdisciplinary Science and Engineering in Health Systems, Okayama University Sunao Hara Graduate school of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masanobu Abe Graduate school of Interdisciplinary Science and Engineering in Health Systems, Okayama University Nobukatsu Hojo NTT Corporation Yusuke Ijima NTT Corporation This paper proposes architectures that facilitate the extrapolation of emotional expressions in deep neural network (DNN)-based text-to-speech (TTS). In this study, the meaning of “extrapolate emotional expressions” is to borrow emotional expressions from others, and the collection of emotional speech uttered by target speakers is unnecessary. Although a DNN has potential power to construct DNN-based TTS with emotional expressions and some DNN-based TTS systems have demonstrated satisfactory performances in the expression of the diversity of human speech, it is necessary and troublesome to collect emotional speech uttered by target speakers. To solve this issue, we propose architectures to separately train the speaker feature and the emotional feature and to synthesize speech with any combined quality of speakers and emotions. The architectures are parallel model (PM), serial model (SM), auxiliary input model (AIM), and hybrid models (PM&AIM and SM&AIM). These models are trained through emotional speech uttered by few speakers and neutral speech uttered by many speakers. Objective evaluations demonstrate that the performances in the open-emotion test provide insufficient information. They make a comparison with those in the closed-emotion test, but each speaker has their own manner of expressing emotion. However, subjective evaluation results indicate that the proposed models could convey emotional information to some extent. Notably, the PM can correctly convey sad and joyful emotions at a rate of >60%. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 9 2 2020 A new telestroke network system in northern area of Okayama prefecture 166 170 EN Ryo Sasaki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshio Omote Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Tsuyama Central Hospital Kazuki Kobayashi Department of Neurosurgery, Tsuyama Central Hospital Takashi Sawata Department of Gastrointestinal Surgery, Tsuyama 1st Hospital Yuki Sato Department of Internal Medicine, Sato Memorial Hospital Junichi Kubota Department of Internal Medicine, Tajiri Hospital Masayuki Mizobuchi Department of Neurosurgery, Kaneda Hospital Takashi Hayashi Department of Orthopedics, Sayo Central Hospital Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background</br> Telestroke network can provide rapid access to specialized treatment and improves on‐site management of acute stroke patients through the “hub‐and‐spoke” model. In the northern part of Okayama Prefecture, there has been a regional gap of stroke care due to the shortage of stroke specialists and facilities. In addition, due to the novel coronavirus disease 2019 (COVID‐19), it is required to reduce the unnecessary contact with stroke patients from other hospitals.</br> Aim</br> We organized a novel cost‐free telestroke network with an image and video sharing for neurological diseases in the northern part of Okayama Prefecture to improve the stroke management in the area.</br> Method</br> We prepared the tablet device on which Skype® application was installed for each hospital and recruited the patients who visited or hospitalized in the spoke hospitals and were suspected to have some neurological diseases from April 2019 to May 2020. The patient's clinical data were recorded and analyzed. </br> Results</br> During the study period, 5 patients were recruited including the cases with the initial diagnosis of stroke or brain tumor. Among them, 2 cases were transferred to the hub hospital, 2 cases were transferred to other hospitals, and 1 case was treated on site under specialist's advice.</br> Conclusion</br> The new telestroke network system may be beneficial for acute stroke management and reducing the unnecessary patient's transfer in the rural area, especially under coexistence with COVID‐19. No potential conflict of interest relevant to this article was reported.

IOP Press Acta Medica Okayama 1387-2877 73 1 2020 A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology 217 227 EN Koji Abe Department of Neurology, Okayama University Jingwei Shang Department of Neurology, Okayama University Xiaowen Shi Department of Neurology, Okayama University Toru Yamashita Department of Neurology, Okayama University Nozomi Hishikawa Department of Neurology, Okayama University Mami Takemoto Department of Neurology, Okayama University Ryuta Morihara Department of Neurology, Okayama University Yumiko Nakano Department of Neurology, Okayama University Yasuyuki Ohta Department of Neurology, Okayama University Kentaro Deguchi Department of Neurology, Okayama City Hospital, Okayama Masaki Ikeda Department of Neurology, Gunma University, Graduate School of Medicine Yoshio Ikeda Department of Neurology, Gunma University, Graduate School of Medicine Koichi Okamoto Department of Neurology, Geriatrics Research Institute and Hospital Mikio Shoji Department of Neurology, Geriatrics Research Institute and Hospital Masamitsu Takatama Department of Neurology, Geriatrics Research Institute and Hospital Motohisa Kojo Department of Neurology, Ako Chuo Hospital Takeshi Kuroda Division of Neurology, Department of Medicine, Showa University, School of Medicine Kenjiro Ono Division of Neurology, Department of Medicine, Showa University, School of Medicine Noriyuki Kimura Department of Neurology, Faculty of Medicine, Oita University Etsuro Matsubara Department of Neurology, Faculty of Medicine, Oita University Yosuke Osakada Department of Neurology, Kurashiki Heisei Hospital Yosuke Wakutani Department of Neurology, Kurashiki Heisei Hospital Yoshiki Takao Department of Neurology, Kurashiki Heisei Hospital Yasuto Higashi Department of Neurology, Himeji Central Hospital Kyoichi Asada Membrane Protein and Ligand Analysis Center, Protosera Inc., Takehito Senga Membrane Protein and Ligand Analysis Center, Protosera Inc., Lyang-Ja Lee Membrane Protein and Ligand Analysis Center, Protosera Inc., Kenji Tanaka Membrane Protein and Ligand Analysis Center, Protosera Inc., Background:</br> Because dementia is an emerging problem in the world, biochemical markers of cerebrospinal fluid (CSF) and radio-isotopic analyses are helpful for diagnosing Alzheimer’s disease (AD). Although blood sample is more feasible and plausible than CSF or radiological biomarkers for screening potential AD, measurements of serum amyloid- β (Aβ), plasma tau, and serum antibodies for Aβ1 - 42 are not yet well established.</br> Objective:</br> We aimed to identify a new serum biomarker to detect mild cognitive impairment (MCI) and AD in comparison to cognitively healthy control by a new peptidome technology.</br> Methods:</br> With only 1.5μl of serum, we examined a new target plate “BLOTCHIP®” plus a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) to discriminate control (n = 100), MCI (n = 60), and AD (n = 99). In some subjects, cognitive Mini-Mental State Examination (MMSE) were compared to positron emission tomography (PET) with Pittsburgh compound B (PiB) and the serum probability of dementia (SPD). The mother proteins of candidate serum peptides were examined in autopsied AD brains.</br> Results:</br> Apart from Aβ or tau, the present study discovered a new diagnostic 4-peptides-set biomarker for discriminating control, MCI, and AD with 87% of sensitivity and 65% of specificity between control and AD (***p < 0.001). MMSE score was well correlated to brain Aβ deposition and to SPD of AD. The mother proteins of the four peptides were upregulated for coagulation, complement, and plasticity (three proteins), and was downregulated for anti-inflammation (one protein) in AD brains.</br> Conclusion:</br> The present serum biomarker set provides a new, rapid, non-invasive, highly quantitative and low-cost clinical application for dementia screening, and also suggests an alternative pathomechanism of AD for neuroinflammation and neurovascular unit damage. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2405-6502 21 2020 A case of type 1 facioscapulohumeral muscular dystrophy (FSHD) with restrictive ventilatory defect and congestive heart failure 100284 EN Nobutoshi Morimoto Department of Neurology, Kagawa Central Prefectural Hospital Mizuki Morimoto Department of Neurology, Kagawa Central Prefectural Hospital Yoshiaki Takahashi Department of Neurology, Kagawa Central Prefectural Hospital Motonori Takamiya Department of Neurology, Kagawa Central Prefectural Hospital Ichizo Nishino Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP) Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University [Background] Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disease characterized by asymmetric involvement of muscles in the face, upper extremity, trunk, and lower extremity regions, with variable severity. It was recently reported that restrictive respiratory involvement is more frequent and severe than previously recognized, while cardiac dysfunction other than arrhythmia is still considered extremely rare in FSHD. [Case report] A 59-year-old man presenting with marked muscle atrophy in the trunk and asymmetrical muscle atrophy in the legs was hospitalized because of dyspnea and edema in the face and limbs. Shortness of breath with body movement started from approximately 40 years of age. Muscle biopsy revealed myopathic change with mild to moderate variation in fiber size. The diagnosis of FSHD was made by D4Z4 contraction to three repeats on genetic testing. A pulmonary function test revealed a decline of forced vital capacity (FVC) and a preserved FEV1/FVC indicating restrictive ventilatory defect (RVD). Ultrasonic echocardiogram (UCG) showed diffuse left ventricular hypokinesis, ventricular septum thickening, pericardial effusion, and decreased ejection fraction (LVEF 30%). [Conclusion] Although restrictive ventilatory defect and congestive heart failure are uncommon in FSHD, respiratory and cardiac evaluation may be necessary in patients with FSHD. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 132 2 2020 サイバーフィジカル情報応用研究コア（Cypher）設立について 92 94 EN Masanobu Abe Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 132 2 2020 ホジキンリンパ腫の治療により神経症状の改善を認めた傍腫瘍性神経症候群の1 例 87 90 EN Ryosuke Ikemachi Department of Hematology, Okayama Red Cross Hospital Kaho Kondo Department of Hematology, Okayama Red Cross Hospital Akihumi Matumura Department of Hematology, Okayama Red Cross Hospital Soichiro Fujii Department of Hematology, Okayama Red Cross Hospital Makoto Takeuchi Department of Hematology, Okayama Red Cross Hospital Kouta Sato Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Abe Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 　An 86-year-old man was admitted to another hospital with ataxia and general fatigue. Brain MRI scan revealed a high-intensity area in the bilateral thalamus, and he was referred to Okayama University Hospital for detailed examination. Cerebrospinal fluid (CSF) and blood tests showed no evidence of infection or autoimmune encephalitis. An FDG-PET/CT scan revealed systemic lymphadenopathy, and cervical lymph node biopsy showed classical Hodgkin lymphoma. Neurological symptoms were suspicious of paraneoplastic neurological syndrome (PNS), but onco-neural antibodies were not detected in either serum or CSF. He was referred to our hospital, Okayama Red Cross Hospital, for treatment and administered 6 cycles of an ABVD regimen, and an FDG-PET/CT scan showed a complete remission. The brain lesion disappeared and neurological symptoms were improved, so he was diagnosed with PNS. PNS is rare complication associated with malignant lymphoma and early diagnosis is important because neurological symptoms can be improved with anti-cancer treatment. No potential conflict of interest relevant to this article was reported.

Nature Research Acta Medica Okayama 2045-2322 10 1 2020 Therapeutic benefit of Muse cells in a mouse model of amyotrophic lateral sclerosis 17102 EN Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Kushida Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine Shohei Wakao Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine Koh Tadokoro Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Emi Nomura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshio Omote Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Takemoto Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nozomi Hishikawa Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Ohta Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mari Dezawa Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine Koji Abe Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss. Muse cells are endogenous reparative pluripotent-like stem cells distributed in various tissues. They can selectively home to damaged sites after intravenous injection by sensing sphingosine-1-phosphate produced by damaged cells, then exert pleiotropic effects, including tissue protection and spontaneous differentiation into tissue-constituent cells. In G93A-transgenic ALS mice, intravenous injection of 5.0x10(4) cells revealed successful homing of human-Muse cells to the lumbar spinal cords, mainly at the pia-mater and underneath white matter, and exhibited glia-like morphology and GFAP expression. In contrast, such homing or differentiation were not recognized in human mesenchymal stem cells but were instead distributed mainly in the lung. Relative to the vehicle groups, the Muse group significantly improved scores in the rotarod, hanging-wire and muscle strength of lower limbs, recovered the number of motor neurons, and alleviated denervation and myofiber atrophy in lower limb muscles. These results suggest that Muse cells homed in a lesion site-dependent manner and protected the spinal cord against motor neuron death. Muse cells might also be a promising cell source for the treatment of ALS patients. No potential conflict of interest relevant to this article was reported.

岡山大学法文学部国語国文学研究室 Acta Medica Okayama 0386-3123 7 1979 長編小説の鑑賞試論――事象（心象）と人間像の相関把握へのアプローチ――”阿部知二「冬の宿」を素材に” 41 56 EN 10.18926/okadaironkou/60700 No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-2466 20 1 2020 Recovery from hypoxemia and Hypercapnia following noninvasive pressure support ventilation in a patient with statin-associated necrotizing myopathy: a case report 156 EN Yuriko Yamamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koh Tadokoro Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Ohta Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Sato Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Yamamura Center for Rheumatology, Okayama Saiseikai General Hospital Ken-Ei Sada Department of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Abe Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Statin-associated necrotizing myopathy (SANM) is a rare autoimmune disorder caused by administration of statins. SANM is characterized by weakness due to necrosis and regeneration of myofibers. Here we report the first case of SANM with acute respiratory failure treated with noninvasive pressure support ventilation in addition to immunosuppressants. <br/> Case presentation: A 59-year-old woman who had been treated with 2.5 mg/day of rosuvastatin calcium for 5 years stopped taking the drug 4 months before admission to our hospital due to elevation of creatine kinase (CK). Withdrawal of rosuvastatin for 1 month did not decrease the level of CK, and she was admitted to our hospital due to the development of muscle weakness of her neck and bilateral upper extremities. Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies were positive. Magnetic resonance imaging showed myositis, and muscle biopsy from the right biceps brachii muscle showed muscle fiber necrosis and regeneration without inflammatory cell infiltration, suggesting SANM. After the diagnosis, she received methylprednisolone pulse therapy (mPSL, 1 g/day × 3 days, twice) and subsequent oral prednisolone therapy (PSL, 30 mg/day for 1 month, 25 mg/day for 1 month and 22.5 mg/day for 1 month), leading to improvement of her muscle weakness. One month after the PSL tapering to 20 mg/day, her muscle weakness deteriorated with oxygen desaturation (SpO2: 93% at room air) due to hypoventilation caused by weakness of respiratory muscles. BIPAP was used for the management of acute respiratory failure in combination with IVIG (20 g/day × 5 days) followed by mPSL pulse therapy (1 g/day × 3 days), oral PSL (30 mg/day × 3 weeks, then tapered to 25 mg/day) and tacrolimus (3 mg/day). Twenty-seven days after the start of BIPAP, she was weaned from BIPAP with improvement of muscle weakness, hypoxemia and hypercapnia. After she achieved remission with improvement of muscle weakness and reduction of serum CK level to a normal level, the dose of oral prednisolone was gradually tapered to 12.5 mg/day without relapse for 3 months. <br/> Conclusions: Our report provides new insights into the role of immunosuppressants and biphasic positive airway pressure for induction of remission in patients with SANM. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 21 6 2020 Prevention of Cognitive Decline in Alzheimer's Disease by Novel Antioxidative Supplements 1974 EN Koh Tadokoro Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruhiko Inufusa Division of Anti-Oxidant Research, Life Science Research Center, Gifu University Alan Foo Nyuk Loon Hovid Berhad Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Oxidative stress plays a crucial role in Alzheimer's disease (AD) from its prodromal stage of mild cognitive impairment. There is an interplay between oxidative stress and the amyloid beta (A beta) cascade via various mechanisms including mitochondrial dysfunction, lipid peroxidation, protein oxidation, glycoxidation, deoxyribonucleotide acid damage, altered antioxidant defense, impaired amyloid clearance, inflammation and chronic cerebral hypoperfusion. Based on findings that indicate that oxidative stress plays a major role in AD, oxidative stress has been considered as a therapeutic target of AD. In spite of favorable preclinical study outcomes, previous antioxidative components, including a single antioxidative supplement such as vitamin C, vitamin E or their mixtures, did not clearly show any therapeutic effect on cognitive decline in AD. However, novel antioxidative supplements can be beneficial for AD patients. In this review, we summarize the interplay between oxidative stress and the A beta cascade, and introduce novel antioxidative supplements expected to prevent cognitive decline in AD. No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2640-009X 2019 2019 Speech-like Emotional Sound Generator by WaveNet 143 147 EN Kento Matsumoto Okayama University Sunao Hara Okayama University Masanobu Abe Okayama University In this paper, we propose a new algorithm to generate Speech-like Emotional Sound (SES). Emotional information plays an important role in human communication, and speech is one of the most useful media to express emotions. Although, in general, speech conveys emotional information as well as linguistic information, we have undertaken the challenge to generate sounds that convey emotional information without linguistic information, which results in making conversations in human-machine interactions more natural in some situations by providing non-verbal emotional vocalizations. We call the generated sounds “speech-like”, because the sounds do not contain any linguistic information. For the purpose, we propose to employ WaveNet as a sound generator conditioned by only emotional IDs. The idea is quite different from WaveNet Vocoder that synthesizes speech using spectrum information as auxiliary features. The biggest advantage of the idea is to reduce the amount of emotional speech data for the training. The proposed algorithm consists of two steps. In the first step, WaveNet is trained to obtain phonetic features using a large speech database, and in the second step, WaveNet is re-trained using a small amount of emotional speech. Subjective listening evaluations showed that the SES could convey emotional information and was judged to sound like a human voice. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 7 5 2019 Late presented congenital myasthenic syndrome with novel compound heterozygous CHRNE mutations mimicking seronegative myasthenia gravis 288 290 EN Yumiko Nakano Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Tsunoda Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Mitsui Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Sato Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Takemoto Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nozomi Hishikawa Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Ohta Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsushi Toda Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoji Tsuji Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Abe Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences We found a late presented congenital myasthenic syndrome (CMS) patient with novel CHRNE gene mutations. Although our patient has shown blepharoptosis since youth, fatigable muscle weakness began at age 71. Genetic analysis revealed novel compound heterozygous CHRNE mutations (c.1032+2T>G, c.1306_1307 delGA). His myasthenic symptoms were well managed by oral anti‐cholinesterase drug until he died at 82‐year‐old. The present case showed mild myasthenic symptoms with very late presentation and slow progression. Late presented CMS is often underdiagnosed; therefore, genetic testing is important to distinguish it from other myasthenic disease. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0360-4012 97 5 2018 Enhanced oxidative stress and the treatment by edaravone in mice model of amyotrophic lateral sclerosis 607 609 EN Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Emi Nomura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tian Feng Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yong Huang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xia Liu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xiaowen Shi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Oxidative stress is associated with the degeneration of both motor neurons and skeletal muscles in amyotrophic lateral sclerosis (ALS). A free radical scavenger edaravone has been proven as a therapeutic drug for ALS patients, but the neuroprotective mechanism for the oxidative stress of ALS has not been fully investigated. In this study, we investigated oxidative stress in ALS model mice bearing both oxidative stress sensor nuclear erythroid 2-related factor 2 (Nrf2) and G93A-human Cu/Zn superoxide dismutase (Nrf2/G93A) treated by edaravone. In vivo Nrf2 imaging analysis showed the accelerated oxidative stress both in spinal motor neurons and lower limb muscles of Nrf2/G93A mice according to disease progression in addition to the enhancement of serum oxidative stress marker dROMS. These were significantly alleviated by edaravone treatment accompanied by clinical improvements (rotarod test). The present study suggests that in vivo optical imaging of Nrf2 is useful for detecting oxidative stress in ALS, and edaravone alleviates the degeneration of both motor neurons and muscles related to oxidative stress in ALS patients. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 7 3 2019 Very rare solitary primary peripheral nerve onset cytotoxic molecule-positive peripheral T-cell lymphoma (PTCL) 146 149 EN Namiko Matsumoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Takahashi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuko Kawahara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Maiko Sakamoto Department of Hematology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eisei Kondou Department of Hematology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rei Shibata Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yoshino Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Here we present the first report of solitary primary peripheral nerve onset cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (PTCL) diagnosed after nerve biopsy. An 84-year-old female with rheumatoid arthritis (RA) complained of asymmetric severe tenderness in her upper limbs. The biopsy pathology revealed a direct invasion of CM-positive PTCL. When RA patients complain of numbness, tenderness, or weakness, lymphomatic peripheral nerve invasion should be considered. No potential conflict of interest relevant to this article was reported.

NPG Acta Medica Okayama 2045-2322 9 1 2019 In vivo direct reprogramming of glial linage to mature neurons after cerebral ischemia 10956 EN Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jingwei Shang Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yumiko Nakano Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuta Morihara Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Sato Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Takemoto Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nozomi Hishikawa Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Ohta Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Abe Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The therapeutic effect of in vivo direct reprogramming on ischemic stroke has not been evaluated. In the present study, a retroviral solution (1.5-2.0 × 107 /ul) of mock pMX-GFP (n = 13) or pMX-Ascl1/Sox2/NeuroD1 (ASN) (n = 14) was directly injected into the ipsilateral striatum and cortex 3 days after 30 min of transient cerebral ischemia. The reprogrammed cells first expressed neuronal progenitor marker Dcx 7 and 21 days after viral injection, then expressed mature neuronal marker NeuN. This was accompanied by morphological changes, including long processes and synapse-like structures, 49 days after viral injection. Meanwhile, therapeutic improvement was not detected both in clinical scores or infarct volume. The present study provides a future novel self-repair strategy for ischemic stroke with beneficial modifications of the inducer-suppressor balance. No potential conflict of interest relevant to this article was reported.

IOS Press Acta Medica Okayama 1387-2877 68 4 2019 Acute Anti-Inflammatory Markers ITIH4 and AHSG in Mice Brain of a Novel Alzheimer's Disease Model 1667 1675 EN Xiaowen Shi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xia Liu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tian Feng Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yong Huang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Alzheimer's disease (AD) is the most common dementia and a progressive neurodegenerative disorder aggravated by chronic hypoperfusion (HP). Since numerous evidence suggests that inflammation is related with AD pathology, we investigated the expression change of two anti-inflammatory markers, inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and alpha-2-HS-glycoprotein (AHSG), in a novel AD model (APP23) with HP at 12 month of age. As compared with wild type (WT, n = 10), immunohistochemical analysis showed a higher ITIH4 and a lower AHSG expressions in the cerebral cortex, hippocampus, and thalamus of the APP23 + HP group (n = 12) than the simple APP23 (n = 10) group (*p < 0.05 and **p < 0.01 versus WT; #p < 0.05 and # #p < 0.01 versus APP23). The present study provides an upregulation of anti-inflammatory ITIH4 and a downregulation of pro-inflammatory TNFα-dependent AHSG in a novel AD plus HP mice model. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 7 3 2018 Multi‐modal combination therapy rescued a frequent ischemic stroke patient due to giant cell arteritis 132 135 EN Yoshiaki Takahashi Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kota Sato Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Namiko Matsumoto Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Yuko Kawahara Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Taijun Yunoki Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Jingwei Shang Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Mami Takemoto Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Nozomi Hishikawa Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Yasuyuki Ohta Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Toru Yamashita Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Koji Abe Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Ischemic stroke (IS) due to giant cell arteritis (GCA) is rare, but highly mortal. Here, we report a 72-year-old man who showed frequent IS with GCA. Initial therapy with prednisolone increased the frequency of IS, which disappeared after continuous multi-modal combination therapy with corticosteroids, immunosuppressive agents, antiplatelets, and statin. The present case was discharged with independent walk, suggesting that a multi-modal combination therapy rescued the GCA patient from frequent IS. No potential conflict of interest relevant to this article was reported.

IOS Press Acta Medica Okayama 1387-2877 71 1 2019 Clinical and Pathological Benefits of Edaravone for Alzheimer's Disease with Chronic Cerebral Hypoperfusion in a Novel Mouse Model 327 339 EN Tian Feng Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xiaowen Shi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Tsunoda Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Emi Nomura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Sasaki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koh Tadokoro Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Namiko Matsumoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Alzheimer's disease (AD) and chronic cerebral hypoperfusion (CCH) often coexist in dementia patients in aging societies. The hallmarks of AD including amyloid-β (Aβ)/phosphorylated tau (pTau) and pathology-related events such as neural oxidative stress and neuroinflammation play critical roles in pathogenesis of AD with CCH. A large number of lessons from failures of drugs targeting a single target or pathway on this so complicated disease indicate that disease-modifying therapies targeting multiple key pathways hold potent potential in therapy of the disease. In the present study, we used a novel mouse model of AD with CCH to investigate a potential therapeutic effect of a free radical scavenger, Edaravone (EDA) on AD with CCH via examining motor and cognitive capacity, AD hallmarks, neural oxidative stress, and neuroinflammation. Compared with AD with CCH mice at 12 months of age, EDA significantly improved motor and cognitive deficits, attenuated neuronal loss, reduced Aβ/pTau accumulation, and alleviated neural oxidative stress and neuroinflammation. These findings suggest that EDA possesses clinical and pathological benefits for AD with CCH in the present mouse model and has a potential as a therapeutic agent for AD with CCH via targeting multiple key pathways of the disease pathogenesis. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 10523057 28 10 2019 Twendee X Ameliorates Phosphorylated Tau, α-Synuclein and Neurovascular Dysfunction in Alzheimer's Disease Transgenic Mice With Chronic Cerebral Hypoperfusion 104310 EN Xia Liu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xiaowen Shi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yong Huang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University BACKGROUND:<br/> The pathological impact of chronic cerebral hypoperfusion (CCH) on Alzheimer's disease (AD) is still poorly understood. In the present study, we investigated the role of CCH on an AD mouse model in phosphorylated tau and α-synuclein pathology, neurovascular unit, cerebrovascular remodeling, and neurovascular trophic coupling. Moreover, examined protective effect of a new antioxidant Twendee X (TwX).<br/> METHODS:<br/> APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors to gradually decrease the cerebral blood flow. The effects of the administration of TwX were evaluated by immunohistochemical analysis and Immunofluorescent histochemistry.<br/> RESULTS:<br/> The present study revealed that the expressions of phospho-tau and phospho-α-synuclein were significantly increased in the APP23 + CCH mice group as compared with wild type and APP23 mice groups (*P < .05 and ⁎⁎P < .01 versus WT; #P < .05 and ##P < .01 versus APP23). In addition, CCH significantly exacerbated MMP-9 activation relating to blood-brain barrier destruction (⁎⁎P < .01 versus WT; #P < .05, and ##P < .01 versus APP23), enhanced neurovascular remodeling, and impaired a neurovascular trophic coupling in the vascular endothelial BDNF expression of the APP23 + CCH group. TwX treatment (20 mg/kg/day, from 4.5 to 12 months) significantly reduced tau and α-synuclein pathologies, ameliorated neurovascular dysfunction compared with APP23 + CCH group.<br/> CONCLUSIONS:<br/> Our findings indicate that administration of a new antioxidative mixture TwX substantially reduced the above neuropathologic abnormalities, suggesting a potential therapeutic benefit of TwX for AD with CCH. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 7 6 2019 A unique stroke case with contralateral sulcal hyperintensity on fluid-attenuated inversion recovery image changed to linear serpiginous structures 351 353 EN Yosuke Osakada Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Takahashi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University An 83-year-old man developed acute ischemic stroke. Brain magnetic resonance imaging (MRI) showed ischemic stroke in the left parietal lobe gyri, but fluid-attenuated inversion recovery (FLAIR) showed hyperintensity in the contralateral right temporal-occipital lobe sulci. Follow-up FLAIR image showed the gradual disappearance of the sulcal hyperintensity in the sulci and changed to linear serpiginous structures. This is a unique stroke case showing transitioned FLAIR findings suggesting that the sulcal hyperintensity findings are more severe and an earlier ischemic condition than the linear serpiginous structures. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 7 4 2019 A pneumococcal meningoencephalitis with a small spleen 215 217 EN Keiichiro Tsunoda Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Sato Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Takahashi Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koh Tadokoro Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Sasaki Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Emi Nomura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Takemoto Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nozomi Hishikawa Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Ohta Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Abe Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Streptococcus pneumoniae is a major cause of bacterial meningitis usually in children or elder adults. We report a case of a 38-year-old man having pneumococcal meningoencephalitis with a small spleen (35 cm(3)), compared to seven previous patients with pneumococcal meningitis in our department. Among the eight patients, four cases were due to sinusitis, but the origin could not be identified in the other four cases, including the present case who was the youngest patient with the smallest splenic size. Of interest in the present analysis was the negative or positive correlation between splenic size and age, with or without sinusitis. This is the first report on pneumococcal meningoencephalitis that takes into consideration age, splenic size, and the origin of infection. No potential conflict of interest relevant to this article was reported.

Taylor and Francis Acta Medica Okayama 0161-6412 41 11 2019 Yoga-plus exercise mix promotes cognitive, affective, and physical functions in elderly people 1001 1007 EN Nozomi Hishikawa Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoriko Takahashi Department of Education, Nippon Ayurveda School Yusuke Fukui Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Tokuchi Department of Occupational Therapy, Okayama Institute for Medical and Technical Sciences Junichi Furusawa Department of Occupational Therapy, Mizunaga Rehabilitation Hospital Mami Takemoto Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Sato Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Ohta Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Abe Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives: <br/> Increased attention is being paid to Asian medicine in balanced total health care. We investigated the effects of mixed exercise including yoga ('Yoga-plus') among elderly individuals. <br/> Methods: <br/> A total of 385 subjects (72 males and 313 females, 75.5 ± 8.7 years old) participated in a 12-month (M) exercise program at a health and welfare center, a day service center, and a nursing home. Cognitive, affective, and physical functions, and activities of daily living (ADL), were compared at baseline (0M), 6M and 12M of exercise intervention. <br/> Results: <br/> Mean scores on the frontal assessment battery, clock drawing test, cube copying test, letter fluency, and category fluency significantly improved after the Yoga-plus intervention, while mini-mental state examination, Hasegawa dementia score-revised, and trail-making test performance were relatively stable. Affective scores on the geriatric depression scale (GDS), apathy scale (AS) and Abe's behavioral and psychological symptoms of dementia were not significantly affected by exercise therapy, but subgroups with higher baseline GDS (GDS ≥ 5) and AS (AS ≥ 16) scores showed a significant improvement after intervention. One-leg standing time and 3-m timed up and go test performance significantly improved after 12M intervention. <br/> Discussion: <br/> Yoga-plus improved cognitive, affective, ADL, and physical functions in a local elderly population, particularly among below-baseline individuals, indicating the benefits of dementia prevention among elderly individuals. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 10523057 28 7 2019 Clinical and Pathological Benefit of Twendee X in Alzheimer's Disease Transgenic Mice with Chronic Cerebral Hypoperfusion 1993 2002 EN Xia Liu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xiaowen Shi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yong Huang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University BACKGROUND:<br/> Multiple pathogeneses are involved in Alzheimer's disease (AD), such as amyloid-β accumulation, neuroinflammation, and oxidative stress. The pathological impact of chronic cerebral hypoperfusion on Alzheimer's disease is still poorly understood.<br/> METHODS:<br/> APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive chronic cerebral hypoperfusion (CCH). The effects of the administration of Twendee X (TwX) were evaluated by behavioral analysis, immunohistochemical analysis, and immunofluorescent histochemistry.<br/> RESULTS:<br/> In the present study, chronic cerebral hypoperfusion, which is commonly found in aged Alzheimer's disease, significantly exacerbated motor dysfunction of APP23 mice from 5 months and cognitive deficit from 8 months of age, as well as neuronal loss, extracellular amyloid-β plaque and intracellular oligomer formations, and amyloid angiopathy at 12 months. Severe upregulations of oxidative markers and inflammatory markers were found in the cerebral cortex, hippocampus, and thalamus at 12 months. Twendee X treatment (20 mg/kg/d, from 4.5 to 12 months) substantially rescued the cognitive deficit and reduced the above amyloid-β pathology and neuronal loss, alleviated neuroinflammation and oxidative stress.<br/> CONCLUSIONS:<br/> The present findings suggested a potential therapeutic benefit of Twendee X for Alzheimer's disease with chronic cerebral hypoperfusion. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0022510X 400 2019 A unique Japanese CPEO family with a novel homozygous m.14819 T > G (p. S25A) substitution 145 147 EN Emi Nomura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koh Tadokoro Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Sasaki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Takahashi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yu-ichi Goto Medical Genome Center (MGC), Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience (NIN), National Center of Neurology and Psychiatry Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山大学大学院法務研究科 Acta Medica Okayama 1881-1485 22 2019 不祥事とコンプライアンスを巡る近時の動向について 13 23 EN Masahiro Otsuki 10.18926/OLR/56571 No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 69 2018 中国国内的阿部规秀死亡报导 19 32 EN Keshi Jiang 10.18926/okadai-bun-kiyou/56090 No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 130 1 2018 第7回日本認知症予防学会学術集会報告 43 44 EN Koji Abe Department of Neurology, Okayama University Graduate School of Medicine, Dentlstry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 129 2 2017 家族性大腸腺腫症術後20年後に小腸癌を発症した1例 111 114 EN Yuusaku Sugihara Department of Gastroenterology and Hepatology, Okayama University Hospital Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Hospital Keita Harada Department of Gastroenterological Surgery, Okayama University Hospital Shiho Takashima Department of Gastroenterology and Hepatology, Okayama University Hospital Daisuke Takei Department of Gastroenterological Surgery, Okayama University Hospital Toshihiro Inokuchi Department of Gastroenterology and Hepatology, Okayama University Hospital Masahiro Takahara Department of Gastroenterology and Hepatology, Okayama University Hospital Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Hospital Yoshiko Mori Division of Endoscopy, Okayama University Hospital Hiroyuki Kishimoto Division of Endoscopy, Okayama University Hospital Takeshi Nagasaka Division of Endoscopy, Okayama University Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Hospital A 58-year-old Japanese man visited a local clinic for the evaluation of a stomachache. He was diagnosed with intestinal obstruction. His medical history included a proctocolectomy at the age of 38 years, due to familial adenomatous polyposis (FAP). He was referred to our institution, where he underwent a computed tomography examination and endoscopy of the small intestine. The pathological diagnosis was adenocarcinoma. No invasive or metastatic lesions were observed. Therefore, partial resection of the ileum with lymphadenectomy and reconstruction of the ileostomy were performed. Pathological examination revealed that the tumor was type 2, pT3 (SS) , pN1, pPM0, pDM0, pRM0, INFb, ly1, v1, pEX0, PN0. Twenty-nine days after the surgery, the patient was diagnosed with lung metastasis and he underwent lung radiofrequency ablation. We suggest that long-term follow-up is necessary for patients after surgery for FAP, because of the risk of malignant disease developing in other organs. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1351-5101 20 5 2013 A novel familial prion disease causing pan-autonomic-sensory neuropathy and cognitive impairment e67 e69 EN Kosuke Matsuzono Yoshio Ikeda Department of Neurology, Okayama University Graduate School of Medicine and Dentistry Wentao Liu Tomoko Kurata Department of Neurology, Okayama University Graduate School of Medicine and Dentistry Shoko Deguchi Kentaro Deguchi Department of Neurology, Okayama University Graduate School of Medicine and Dentistry Koji Abe Department of Neurology, Okayama University Graduate School of Medicine and Dentistry No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 3 2016 模擬患者（SP）参加型教育の実践 221 225 EN Toshiko Yoshida Center for the Development of Medical and Health Care Education（ Dental Education）, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2016 Sound collection systems using a crowdsourcing approach to construct sound map based on subjective evaluation EN Sunao Hara Graduate school of Natural Science and Technology, Okayama University Shota Kobayashi Graduate school of Natural Science and Technology, Okayama University Masanobu Abe Graduate school of Natural Science and Technology, Okayama University This paper presents a sound collection system that uses crowdsourcing to gather information for visualizing area characteristics. First, we developed a sound collection system to simultaneously collect physical sounds, their statistics, and subjective evaluations. We then conducted a sound collection experiment using the developed system on 14 participants. We collected 693,582 samples of equivalent Aweighted loudness levels and their locations, and 5,935 samples of sounds and their locations. The data also include subjective evaluations by the participants. In addition, we analyzed the changes in sound properties of some areas before and after the opening of a large-scale shopping mall in a city. Next, we implemented visualizations on the server system to attract users’ interests. Finally, we published the system, which can receive sounds from any Android smartphone user. The sound data were continuously collected and achieved a specified result. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 3 2016 Structure of a New Palatal Plate and the Artificial Tongue for Articulation Disorder in a Patient with Subtotal Glossectomy 205 211 EN Ken-ichi Kozaki Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shigehisa Kawakami Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Konishi Division of Physical Medicine and Rehabilitation, Okayama University Hospital Keiji Ohta Dental Laboratory Division, Okayama University Hospital Jitsuro Yano Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoo Onoda Department of Otolaryngology-Head and Neck Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Matsumoto Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuyoshi Mizukawa Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Hospital Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazunori Nishizaki Department of Otolaryngology-Head and Neck Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Iida Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akio Gofuku Graduate School of Natural Science and Technology, Okayama University Masanobu Abe Department of Computer Science, Okayama University Shogo Minagi Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Dream Speech Project Case Report 10.18926/AMO/54420 A palatal augmentation prosthesis (PAP) is used to facilitate improvement in the speech and swallowing functions of patients with tongue resection or tongue movement disorders. However, a PAPʼs effect is limited in cases where articulation disorder is severe due to wide glossectomy and/or segmental mandibulectomy. In this paper, we describe speech outcomes of a patient with an articulation disorder following glossectomy and segmental mandibulectomy. We used a palatal plate (PP) based on a PAP, along with an artificial tongue (KAT). Speech improvement was evaluated by a standardized speech intelligibility test consisting of 100 syllables. The speech intelligibility score was significantly higher when the patient wore both the PP and KAT than when he wore neither (p＝0.013). The conversational intelligibility score was significantly improved with the PP and KAT than without PP and KAT (p＝0.024). These results suggest that speech function can be improved in patients with hard tissue defects with segmental mandibulectomy using both a PP and a KAT. The nature of the design of the PP and that of the KAT will allow these prostheses to address a wide range of tissue defects. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2015 A Spoken Dialog System with Redundant Response to Prevent User Misunderstanding 223 226 EN Masaki Yamaoka Sunao Hara Masanobu Abe We propose a spoken dialog strategy for car navigation systems to facilitate safe driving. To drive safely, drivers need to concentrate on their driving; however, their concentration may be disrupted due to disagreement with their spoken dialog system. Therefore, we need to solve the problems of user misunderstandings as well as misunderstanding of spoken dialog systems. For this purpose, we introduced a driver workload level in spoken dialog management in order to prevent user misunderstandings. A key strategy of the dialog management is to make speech redundant if the driver’s workload is too high in assuming that the user probably misunderstand the system utterance under such a condition. An experiment was conducted to compare performances of the proposed method and a conventional method using a user simulator. The simulator is developed under the assumption of two types of drivers: an experienced driver model and a novice driver model. Experimental results showed that the proposed strategies achieved better performance than the conventional one for task completion time, task completion rate, and user’s positive speech rate. In particular, these performance differences are greater for novice users than for experienced users. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 2 2015 第26回日本脳循環代謝学会総会報告 161 162 EN Koji Abe No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 69 3 2015 Eosinophil Cationic Protein Shows Survival Effect on H9c2 Cardiac Myoblast Cells with Enhanced Phosphorylation of ERK and Akt/GSK-3β under Oxidative Stress 145 153 EN Hiroko Ishii Shigeshi Kamikawa Satoshi Hirohata Akifumi Mizutani Koji Abe Masaharu Seno Toshitaka Oohashi Yoshifumi Ninomiya Original Article 10.18926/AMO/53521 Eosinophil cationic protein (ECP) is well known as a cationic protein contained in the basic granules of activated eosinophils. Recent studies have reported that ECP exhibits novel activities on various types of cells, including rat neonatal cardiomyocytes. Here we evaluated the effects of ECP on rat cardiac myoblast H9c2 cells. Our results showed that ECP enhanced the survival of the cells, in part by promoting the ERK and Akt/GSK-3β signaling pathways. ECP attenuated the cytotoxic effects of H2O2 on H9c2 cells as well as the production of reactive oxygen species, the number of apoptotic cells and caspase 3/7 activity in the cells. In conclusion, ECP activated the ERK and Akt/GSK-3β pathways, resulting in anti-oxidative effects on H9c2 cells that attenuated apoptosis. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2015 Study on Luteolysis Mechanisms via Lymphatic Vessels in Cow EN Hironori Abe No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2015 Phase Behavior and Solvation Properties in Inhomogeneous Fluids EN Kiharu Abe No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2015 Sound collection and visualization system enabled participatory and opportunistic sensing approaches 390 395 EN Sunao Hara Masanobu Abe Noboru Sonehara This paper presents a sound collection system to visualize environmental sounds that are collected using a crowd-sourcing approach. An analysis of physical features is generally used to analyze sound properties; however, human beings not only analyze but also emotionally connect to sounds. If we want to visualize the sounds according to the characteristics of the listener, we need to collect not only the raw sound, but also the subjective feelings associated with them. For this purpose, we developed a sound collection system using a crowdsourcing approach to collect physical sounds, their statistics, and subjective evaluations simultaneously. We then conducted a sound collection experiment using the developed system on ten participants.We collected 6,257 samples of equivalent loudness levels and their locations, and 516 samples of sounds and their locations. Subjective evaluations by the participants are also included in the data. Next, we tried to visualize the sound on a map. The loudness levels are visualized as a color map and the sounds are visualized as icons which indicate the sound type. Finally, we conducted a discrimination experiment on the sound to implement a function of automatic conversion from sounds to appropriate icons. The classifier is trained on the basis of the GMM-UBM (Gaussian Mixture Model and Universal Background Model) method. Experimental results show that the F-measure is 0.52 and the AUC is 0.79. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 126 3 2014 慢性頭痛の診療ガイドライン 237 239 EN Tohru Matsuura Koji Abe No potential conflict of interest relevant to this article was reported.

Elsevier Science Bv Acta Medica Okayama 0006-8993 1473 2012 Impaired response of hypoxic sensor protein HIF-1 alpha and its downstream proteins in the spinal motor neurons of ALS model mice 55 62 EN Kota Sato Nobutoshi Morimoto Tomoko Kurata Takafumi Mimoto Kazunori Miyazaki Yoshio Ikeda Koji Abe We have recently reported spinal blood flow-metabolism uncoupling in an amyotrophic lateral sclerosis (ALS) animal model using Cu/Zn-superoxide dismutase 1 (SOD1)-transgenic (Tg) mice, suggesting a relative hypoxia in the spinal cord. However, the hypoxic stress sensor pathway has not been well studied in ALS. Here, we examined temporal and spatial changes of the hypoxic stress sensor proteins HIF-1 alpha and its downstream proteins (VEGF, HO-1, and EPO) during the normcodccourse of motor neuron (MN) degeneration in the spinal cord of these ALS model mice. We found that HIP-1 alpha protein expression progressively increased both in the anterior large MNs and the surrounding glial cells in Tg mice from early symptomatic 14 week (W) and end stage 18W. Double immunofluorescence analysis revealed that HIP-1 alpha, plus GFAP and Iba-1 double-positive surrounding glial cells, progressively increased from 14 W to 18 W, although the immunohistochemistiy in large MNs did not change. Expression levels of VEGF and HO-1 also showed a progressive increase but were significant only in the surrounding glial cells at 18W. In contrast, EPO protein expression was decreased in the surrounding glial cells of Tg mice at 18W. Because HIF1-alpha serves as an important mediator of the hypoxic response, these findings indicate that MNs lack the neuroprotective response to hypoxic stress through the HIF-1 alpha system, which could be an important mechanism of neurodegeneration in ALS. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0360-4012 92 1 2014 Reducing Hemorrhagic Complication by Dabigatran Via Neurovascular Protection After Recanalization With Tissue Plasminogen Activator in Ischemic Stroke of Rat 46 53 EN Syoichiro Kono Kentaro Deguchi Yoshio Omote Taijun Yunoki Toru Yamashita Tomoko Kurata Yoshio Ikeda Koji Abe This study assesses the risks and benefits of tissue plasminogen activator (tPA) treatment under oral anticoagulation with dabigatran compared with warfarin or vehicle control in transient middle cerebral artery occlusion (tMCAO). After pretreatment with warfarin (0.2 mg/kg/day), dabigatran (20 mg/kg/day), or vehicle (0.5% carboxymethyl cellulose sodium salt) for 7 days, tMCAO was induced for 120 min, followed by reperfusion and tPA (10 mg/kg/10 ml). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. At 24 hr after reperfusion, markers for the neurovascular unit at the peri-ischemic lesion were immunohistochemically examined in brain sections, and MMP-9 activity was measured by zymography. Paraparesis and intracerebral hemorrhage volume were significantly improved in the dabigatran-pretreated group compared with the warfarin-pretreated group. A marked dissociation between astrocyte foot processes and the basal lamina or pericyte was observed in the warfarin-pretreated group, which was greatly improved in the dabigatran-pretreated group. Furthermore, a remarkable activation of MMP-9 in the ipsilateral warfarin-pretreated rat brain was greatly reduced in dabigatran-pretreated rats. The present study reveals that the mechanism of intracerebral hemorrhage with warfarin-pretreatment plus tPA in ischemic stroke rats is the dissociation of the neurovascular unit, including the pericyte. Neurovascular protection by dabigatran, which was first shown in this study, could partially explain the reduction in hemorrhagic complication by dabigatran reported from clinical study. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0039-2499 43 6 2012 Clinical and Pathological Improvement in Stroke-Prone Spontaneous Hypertensive Rats Related to the Pleiotropic Effect of Cilostazol 1639 1646 EN Yoshio Omote Kentaro Deguchi FengFeng Tian Hiromi Kawai Tomoko Kurata Toru Yamashita Yasuyuki Ohta Koji Abe Background and Purpose-Cerebral infarction is a major cause of death or decreasing activities of daily living. This study aimed to investigate the efficacy of commonly used antiplatelet drugs on stroke and motor and cognitive functions in relation to oxidative stress markers and insulin-like growth factor 1 receptor (IGF-1R). Methods-Stroke-prone spontaneously hypertensive rats were treated with vehicle, aspirin, clopidogrel, and cilostazol from 8 to 10 weeks of age. Physiological parameters, regional cerebral blood flow, and serum lipids were examined. Motor and cognitive functions were evaluated weekly by the Rotorod and water maze task. Spontaneous infarct volume, oxidative stress markers for lipid, protein, and DNA at the ischemic boundary zone of spontaneous infarction, and the IGF-1R-positive cell ratio in the hippocampus were immunohistochemically examined in brain sections. IGF-1R beta expression in the hippocampus was assessed by Western blotting. Results-The antiplatelet drugs, cilostazol and clopidogrel, reduced the spontaneous infarct volume more than aspirin. Only cilostazol improved motor and cognitive functions with a significant increase (P<0.05) in the memory-related IGF-1R-positive ratio and IGF-1R beta expression in the hippocampus. Cilostazol reduced the 4 oxidative stress markers in affected neurons in stroke-prone spontaneously hypertensive rats regardless of blood pressure, regional cerebral blood flow, or serum lipid levels. Conclusions-The present results suggest that a possible pleiotropic effect of cilostazol resulted in the reduction of spontaneous infarct volume and preservation of motor and spatial cognitive functions. The increase of IGF-1R-positive cells in the hippocampal CA1 region could partly explain the preservation of spatial cognitive function in stroke-prone spontaneously hypertensive rats. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 126 2 2014 認知症の治療ガイドライン 155 157 EN Tomoko Kurata Koji Abe No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 126 2 2014 直腸腫瘍を契機に発見された無症状の成人右側Bochdalek孔ヘルニアの１例 137 141 EN Hiroshi Kato Masahiro Oishi Masahito Kodera Masao Yamamura Hideaki Ikeda Kenji Mizuno Yutaka Yamashita Kazunori Suzuki 　We encountered a patient with an adult Bochdalek hernia discovered asymptomatically. A 77-year-old Japanese woman visited a local clinic with chief complaints of melena and difficulty in defecation. Based on the results of the detailed examination in our hospital, she was diagnosed with a rectal gastrointestinal stromal tumor (GIST) with a concurrent asymptomatic adult right-sided Bochdalek hernia. Because the tumor was large, laparoscopic abdominoperineal rectal amputation was performed after systemic imatinib therapy. During the surgery, we found a right diaphragmatic defect more than 13cm in long dia., through which the right hepatic lobe, colon, and greater omentum had prolapsed into the right thoracic cavity. No visceral adhesions were noted. No hernia sac was observed. Adult Bochdalek hernia is a relatively rare condition, and only three (incidentally discovered) cases of asymptomatic Bochdalek hernia, including the present case, have been reported in Japan. Here we provide a case report for the patient, who was followed-up without hernia surgery, plus a review of the literature. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 126 2 2014 性同一性障害に対する包括的治療 109 115 EN Yuzaburo Namba No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 126 1 2014 てんかん治療ガイドラインについて 55 58 EN Nobutoshi Morimoto Koji Abe No potential conflict of interest relevant to this article was reported.

岡山大学国際センター, 岡山大学教育開発センター, 岡山大学言語教育センター, 岡山大学キャリア開発センター Acta Medica Okayama 1881-5952 9 2013 英語新カリキュラムのスキル別科目に関するアンケート調査 111 122 EN Yoshi Kenmotsu Junko Otoshi Masatoshi Abe Masaru Ogino Masako Teranishi Mariko Uzuka 10.18926/52195 　岡山大学では平成25年度入学者から英語新カリキュラムを導入し、新１年生のスキル別科目の「総合英語１－４」（スピーキング、リーディング、ライティング、リスニング）は習熟度別クラス編成を行っている。本稿は、言語教育センター英語系が前期末の７月に実施した授業満足度に関するアンケート調査結果を分析したものである。入学時４月のTOEIC IP スコア395点以下、400点以上595点以下、600点以上の習熟度別グループに分け て学生の授業満足度の平均値をみると、習熟度の低いグループよりも高いグループの満足度が高い傾向がみられた。また、授業満足度に影響を与える要因は、習熟度別グループおよび担当教員グループによって異なることがわかった。 No potential conflict of interest relevant to this article was reported.

Elsevier Science Bv Acta Medica Okayama 0006-8993 1397 2011 In vivo optical imaging for evaluating the efficacy of edaravone after transient cerebral ischemia in mice 66 75 EN Ning Liu Jingwei Shang Fengfeng Tian Hiroyoshi Nishi Koji Abe Detection and protection of apoptosis, autophagy and neurovascular unit (NVU) are essentially important in understanding and treatment for ischemic stroke patients. In this study, we have conducted an in vivo optical imaging for detecting apoptosis and activation of matrix metalloproteinases (MMPs), then evaluated the protective effect of 2 package types of free radical scavenger edaravone (A and B) on apoptosis, autophagy and NVU in mice after transient middle cerebral artery occlusion (tMCAO). As compared to vehicle treatment, edaravones A and B showed a significant improvement of clinical scores and infarct size at 48 h after 90 min of tMCAO with great reductions of in vivo fluorescent signal for MMPs and early apoptotic annexin V activations. Ex vivo imaging of MMPSense 680 or annexin V-Cy5.5 showed a fluorescent signal, while which was remarkably different between vehicle and edaravone groups, and colocalized with antibody for MMP-9 or annexin V. Edaravone A and B ameliorated the apoptotic neuronal cell death in immunohistochemistry, and activations of MMP-9 and aquaporin 4 with reducing autophagic activations of microtubule-associated protein 1 light chain 3 (LC3) in Western blot. In this study, edaravone in both packages showed a similar strong neuroprotection after cerebral ischemia, which was confirmed with in vivo and ex vivo optical imagings for MMPs and annexin V as well as reducing cerebral infarct, inhibiting apoptotic/autophagic mechanisms, and protecting a part of neurovascular unit. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 125 3 2013 細菌性髄膜炎の治療ガイドライン 257 258 EN Yoshio Ikeda Koji Abe No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 125 2 2013 脳梗塞の治療ガイドライン 159 162 EN Kentaro Deguchi Koji Abe No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0306-4522 221 2012 Strong neuroprotection with a novel platinum nanoparticle against ischemic stroke- andtissue plasminogen activator-related brain damages in mice 47 55 EN M. Takamiya Y. Miyamoto T. Yamashita K. Deguchi Y. Ohta K. Abe Reactive oxygen species (ROS) are major exacerbation factor in acute ischemic stroke, and thrombolytic agent tissue plasminogen activator (tPA) may worsen motor function and cerebral infarcts. The platinum nanoparticle (nPt) is a novel ROS scavenger, and thus we examined the clinical and neuroprotective effects of nPt in ischemic mouse brains. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min and divided into the following four groups by intravenous administration upon reperfusion, vehicle, tPA, tPA + nPt, and nPt. At 48 h after tMCAO, motor function, infarct volume, immunohistochemical analyses of neurovascular unit (NVU), in vivo imaging of matrix metalloproteinase (MMP), and zymography for MMP-9 activity were examined. Superoxide anion generation at 2 h after tMCAO was also examined with hydroethidine (HEt). As a result, administration of tPA deteriorated the motor function and infarct volume as compared to vehicle. In vivo optical imaging of MMP showed strong fluorescent signals in affected regions of tMCAO groups. Immunohistochemical analyses revealed that tMCAO resulted in a minimal decrease of NAGO and occludin, but a great decrease of collagen IV and a remarkable increase of MMP-9. HEt stain showed increased ROS generation by tMCAO. All these results became pronounced with tPA administration, and were greatly reduced by nPt. The present study demonstrates that nPt treatment ameliorates neurological function and brain damage in acute cerebral infarction with neuroprotective effect on NVU and inactivation of MMP-9. The strong reduction of ROS production by nPt could account for these remarkable neurological and neuroprotective effects against ischemic stroke. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1554-8627 6 8 2010 In vivo imaging of autophagy in a mouse stroke model 1107 1114 EN FengFeng Tian Kentaro Deguchi Toru Yamashita Yasuyuki Ohta Nobutoshi Morimoto Jingwei Shang Xuemei Zhang Ning Liu Yoshio Ikeda Tohru Matsuura Koji Abe Recent studies have suggested that autophagy is involved in a neural death pathway following cerebral ischemia. In vivo detection of autophagy could be important for evaluating ischemic neural cell damage for human stroke patients. Using novel green fluorescent protein (GFP)-fused microtubule-associated protein 1 light chain 3 (LC3) transgenic (Tg) mice, in vivo imaging of autophagy was performed at 1, 3 and 6 d after 60 min transient middle cerebral artery occlusion (tMCAO). Ex vivo imaging of autophagy, testing of the autophagy inhibitor 3-methyladenine (3-MA), estern blot analysis, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) and fluorescent analyses were performed on brain sections following tMCAO. In vivo fluorescent signals were detected above the ischemic hemisphere through the skull bone at 1, 3 and 6 d after tMCAO, with a peak at 1 d. Similar results were obtained with ex vivo fluorescence imaging. western blot analysis revealed maximum LC3-I and LC3-II expression at 1 d after tMCAO and fluorescence immunohistochemistry demonstrated that GFP-LC3-positive cells were primarily neuronal, not astroglial or microglial, cells. The number of GFP-LC3/TUNEL double-positive cells was greater in the peri-ischemic area than in the core. These results provided evidence of in vivo autophagy detection, with a peak at 1 d, in a live animal model following cerebral ischemia. This novel technique could be valuable for monitoring autophagic processes in vivo in live stroke patients, as well as for clarifying the detailed role of autophagy in the ischemic brain, as well as in other neurological diseases. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 125 1 2013 パーキンソン病の治療ガイドライン 69 71 EN Tomoko Kurata Koji Abe No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 124 1 2012 手足口病の合併症 83 85 EN Nobuko Yamashita No potential conflict of interest relevant to this article was reported.

情報処理学会 Acta Medica Okayama 09196072 2005 94 2005 分類の根拠を明示した動詞語彙概念構造辞書の構築 123 130 EN Koichi Takeuchi Kentaro Inui Atsushi Fujita Nao Takeuchi Shuya Abe 本研究では語彙概念構造を利用した動詞の辞書データベースを構築する．語彙概念構造は構文上での語の振る舞いを基に意味構造を記述するもので，こうした辞書データは言語処理において特に言語生成，例えば翻訳や言い換え，要約といった応用に必須となる言語資源である．提案する辞書データは語彙概念構造のみを記述するのではなく，語彙概念構造の分析で明らかにする語の振る舞い，ならびに分析の基となる統語テストを記述するため，分類根拠がわかりやすく透明性の高い辞書データとなることが期待できる． No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2011 キウイフルーツ果実における抗糖尿病作用と抗酸化能に関する研究 EN Daigo Abe No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 123 3 2011 神経内科領域の難治性疾患診療 227 230 EN Yoshio Ikeda Koji Abe No potential conflict of interest relevant to this article was reported.

Elsevier Sci Ltd. Acta Medica Okayama 0021-9290 42 13 2009 Mechanical stretch stimulates integrin αVβ3-mediated collagen expression in human anterior cruciate ligament cells 2097 2103 EN Tomonori Tetsunaga Takayuki Furumatsu Nobuhiro Abe Keiichiro Nishida Keiji Naruse Toshifumi Ozaki Biomechanical stimuli have fundamental roles in the maintenance and remodeling of ligaments including collagen gene expressions. Mechanical stretching signals are mainly transduced by cell adhesion molecules such as integrins. However, the relationships between stress-induced collagen expressions and integrin-mediated cellular behaviors are still unclear in anterior cruciate ligament cells. Here, we focused on the stretch-related responses of different cells derived from the ligament-to-bone interface and midsubstance regions of human anterior cruciate ligaments. Chondroblastic interface cells easily lost their potential to produce collagen genes in non-stretched conditions, rather than fibroblastic midsubstance cells. Uni-axial mechanical stretches increased the type I collagen gene expression of interface and midsubstance cells up to 14- and 6-fold levels of each non-stretched control, respectively. Mechanical stretches also activated the stress fiber formation by shifting the distribution of integrin αVβ3 to the peripheral edges in both interface and midsubstance cells. In addition, integrin αVβ3 colocalized with phosphorylated focal adhesion kinase in stretched cells. Functional blocking analyses using anti-integrin antibodies revealed that the stretch-activated collagen gene expressions on fibronectin were dependent on integrin αVβ3-mediated cellular adhesions in the interface and midsubstance cells. These findings suggest that the integrin αVβ3-mediated stretch signal transduction might have a key role to stimulate collagen gene expression in human anterior cruciate ligament, especially in the ligament-to-bone interface. No potential conflict of interest relevant to this article was reported.

Academic Press Inc Elsevier Science Acta Medica Okayama 0006-291X 402 2 2010 Combined use of bFGF and GDF-5 enhances the healing of medial collateral ligament injury 329 334 EN Kenta Saiga Takayuki Furumatsu Aki Yoshida Shin Masuda Shota Takihira Nobuhiro Abe Toshifumi Ozaki Basic fibroblast growth factor (bFGF) and growth and differentiation factor (GDF)-5 stimulate the healing of medial collateral ligament (MCL) injury. However, the effect of isolated and combined use of bFGF/GDF-5 remains still unclear. We investigated cellular proliferation and migration responding to bFGF/GDF-5 using rabbit MCL fibroblasts. Rabbit MCL injury was treated by bFGF and/or GDF-5 with peptide hydrogels. Gene expression and deposition of collagens in healing tissues were evaluated. bFGF/GDF-5 treatment additively enhanced cell proliferation and migration. bFGF/GDF-5 hydrogels stimulated Col1a1 expression without increasing Col3a1 expression. Combined use of bFGF/GDF-5 stimulated type I collagen deposition and the reorganization of fiber alignment, and induced better morphology of fibroblasts in healing MCLs. Our study indicates that combined use of bFGF/GDF-5 might enhance MCL healing by increasing proliferation and migration of MCL fibroblasts, and by regulating collagen synthesis and connective fiber alignment. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 65 4 2011 Therapeutic Approaches to Vascular Protection in Ischemic Stroke 219 223 EN Toru Yamashita Koji Abe Review 10.18926/AMO/46846 Reperfusion with recombinant tissue plasminogen activator (tPA) sometimes causes catastrophic hemorrhagic transformation (HT) in the ischemic brain. Consequently, the application of tPA has been strictly limited. Recent studies have indicated that matrix metalloproteinases (MMPs), especially MMP-9, play a critical role in blood brain barrier (BBB) disruption in the ischemic brain, leading to brain edema and HT. In the ischemic brain, free radicals and exogenous tPA itself can trigger MMP-9 activation through several signaling pathways containing LDL receptor-related protein (LRP) and proteinase-activated receptor 1 (PAR1). Therapeutic targeting of free radicals and MMP-9/t-PA related signaling pathways might be promising approaches to minimizing catastrophic HT in acute stroke patients. We provide an overview of the available scientific reports to improve our understanding of the mechanisms leading to HT, and highlight recent progress in the development of new therapeutic strategies for preventing HT in the post-stroke brain. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 123 2 2011 上腕骨外側上顆炎の診療ガイドライン 141 144 EN Yasunori Shimamura Madoka Inoue Masatugu Ozawa Tomoko Kanazawa Taiichi Saitou Ryuichi Nakahara Tomoyuki Noda Keiichiro Nishida Toshifumi Ozaki No potential conflict of interest relevant to this article was reported.

岡山実験動物研究会 Acta Medica Okayama 25 2009 アユモドキの“淡水回遊”と氾濫原環境への適応～吉井川水系における生態学的研究～ 31 34 EN Tsukasa Abe No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 49 11 1937 岡山縣下ニ於ケル腸チフス豫防ニ對スル異種菌經口免疫實施成績ニ就テ 2323 2333 EN M. Shimizu Y. Miki K. Asanuma K. Abe F. Miyagawa S. Murakami, Y. Miki, and F. Miyagawa proved that there is a remarkable output of heteroantibody against typhoid, paratyphoid A and B, and dysentery bacilli in the animal experiment, they proceeded in 1934 to experiment with cocktyphoid-bacilli which had been obtained from cocks that had died of cocktyphoid. They were also highly successful in bringing about a state of immunity from typhoid when applying the same bacilli to rabbits. We therefore resolved to use it upon human beings, and put it into practice, per os, with 9252 peoples in all, in April, 1936. Those treated were ordinary citizens and factory-hands. As to the result, we knew that we might disregard such by-effect of the vaccinationstomach-ache, headache, diarrhoea, etc. -as we found in a mild form. When, at the end of the November of the same year, we investigated the cases of 7486 of those who had been thus vaccinated whit a view to ascertaining if there had been any outbreak of typhoid, paratyphoid A and B, or dysentery (for we cousidered that the vaccine has some influence on the latter disease also), we found among the workmen-class no outbreak of the above-mentioned diseases in the case of those who had taken the cocktyphoid-vaccine, while there were 2 dysentery patients among those who had taken Heterogen. In the case of the ordinary citizens there had occurred one typhoid and one dysentery case among those who had taken bile and the cocktyphoid-vaccine. The number of victims was, moreover, far less than among those who had not been vaccinated. What is more, the patients made very good progress. Thus we believe that the cocktyphoid-vaccine may be successfully applied orally to the human body. As for its effect upon dysentery, we consider that this should be made the subject of further study in the future. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 49 3 1937 昭和10年晩夏岡山市地方ニ流行シタルー熱性黄疸病ニ就テ 635 642 EN S. Murakami Y. Miki T. Abe There occurred an epidemic of a kind of feveric jaundice in some parts of Okayama City and its vicinity from the later part of Summer till early autumn 1935. As we had never learned such an outbreak of such an epidemic in these districts, we wished to make it clear. We have studied it under the guidance of Prof. M. Suzuki and our study as a whole resulted as follows: 1) To our regret, we could not succeed in isolating the causal agent. This may be we think, for when we set about the study, the epidemic had already come to its closing period. 2) The clinical symptoms of this disease, we observed, were quite identical with those of the Sakushu fever. 3) And as the serological tests we examined the Pfeiffers phenomenon test and the agglomeration reaction on 12 cases and obtained: 7 positive reaction with Akiyami repto. type A. 3 positive reaction with Akiyami repto. type B. these 10 negative reaction with repto. ict. haemorrha. and the rest 2 of 12 cases gave negative reaction with any of these reptospiras. 4) We cannot yet dare to describe clearly from the epidemiological point of view why such a prevalence of this disease broke out in 1935, but it might be regarded as remarkable facts to indicate some relationship between the great inundation and the epidemic that the infected locality was visited by a disastrous inundation in the preceding year, that the upper course district of the flooded river Asahi was known as the region influenced by the Sakushu fever, and that the infected parts of Okayama City borders the suburbs where a great number of the rats, regarded as the mediators of the Sakushu fever are living, etc. You will have still more reports after our further study in the future. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 123 1 2011 膝前十字靭帯損傷 53 55 EN Nobuhiro Abe No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 53 6 1941 Rhodeus lanceolataニ寄生スル吸蟲類被嚢幼蟲ノ研究（第2編）Rhodeus lanceolataニ寄生スル吸蟲類被嚢幼蟲ノ種類竝ニ其ノ部位別寄生率ニ就テ 1206 1219 EN Takatomo Abe Von 1934 an hat Verfasser auf Anraten von Prof. M. Suzuki. die Untersuchungen über enzystierten Zerkarien von Trematoden in Rhodeus lanceolata in Provinz Okayama durchgeführt und konnte die oben genannte Untersuchung nachforschen. Die Arten der Metazerkarien wurden folgenderweise eingeteilt, d.h. 1) Sog. Hasegawa'sche neue Art von Stammnosoma, 2) Stammnosoma armatum, 3) Exorchis oviformis, 4) Clonorchis sinensis, 5) Metagonimus takahashii, 6) Echinochasmus japonicus, 7) Cyatocotyle b Hasegawa, 8) Exorchis (Pseudexorchis) major, 9) Echinochasmus perfoliatus, 10) Sog. Hasegawa'sches unklares Distomum c, 11) Sog. Hasegawa'sches unklares Distomum a, 12) Cyatocotyle c Hasegawa, 13) Sog. Hasegawa'sches unklares Distomum b, 14) Cyatocotyle a Hasegawa, 15) Asymphylodora tincae. Von denen fand Verfasser 9 neuartige Metazerkarien in diesen Fischen, die in der obenstehenden Einteilung als 5), 8), 10), 11), 12), 13), 14), 15) geschrieben wurden. In Rhodeus lanceolata gibt es nach der Literatur noch 7 andere Arten der Metazerkarien und so konnte Verfasser darauf finden, das die in Rhodeus lanceolata enzystierten Zerkarien. insgesammt nicht so geringer als die in Pseudorasbora parva sind, denen Arten im Allgemeinen bis her als die zahlreichste gewusst waren. Über die Dichtheit von Metazerkarien hat Verfasser die Ordnung der Infektionskooffizienten von jeder Art und Körpespartien der Fischen, also hat Verfasser gefunden, dass Rhodeus lanceolata der Hauptzwischenwirt von Stammnosoma Arten ist. Die Metazerkarienzahl von Clonorchis sinensis war auch mässig gross. Die Metazerkarienzahl von Clonorchis sinensis war auch mässig gross. Aus diesem Grund der Verfasser überzeugt davon, dass Rhodeus lanceolata die wichtigste Art von Süsswasserfischen nicht nur aus profilaktischem Standpunkt, sondern auch als das Material der Studierung von Trematoden ist. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 53 5 1941 Rhodeus lanceolataニ寄生スル吸蟲類被嚢幼蟲ノ研究（第1編）Rhodeus lanceolataニ寄生スル吸蟲類被嚢幼蟲ノ季節的消長ニ就テ 956 1038 EN Takatomo Abe Auf Antrafen von Dr. M. Suzuki bat Verfasser seit 1934 die Untersuchungen uüber enzystierten Zerkarien von Trematoden in Rhodeus lanceolata in Provinz Okayama durchgeführt und von 5, Januar 1936 bis 20 Dezember 1936 hat Verfasser ein ganzes Jahr hindurch die oben gannante Untersuchung auch unter der Freundlichsten Leitung von Dr. M. Suzuki nachgeforscht. Die Gesammtzahl von Rhodeus lanceolata krumeus und R. 1. moriokae, die Verfasser im Flues für Bewässerung der Reisfelder im Okita-son, Jodo-gun, Okayama-ken, zwei- oder dreimal monatlich und jedesmal je 10 Fische (jeder Fisch etw. 5,75-3,2cm lang) ansammelten, beträgt 250. Jeder Fisch wurde, in 9 Partien verteilt, untersucht -d. h. Kopfeteil, Muskel am Rumpf, Kiemen und Kiemenplatte, Schüppen, Rückenflosse, Brustflossen, Bauchflossen, Gesässflossen und Schwanzflosse. Die drei Ersten wurden mit die vom Verfasser modifizierten Künstlichen Magensaft (Pepsin 0,3. HCl 0,4, Aq. dest. 100,0) verdant und dann untersucht, aber die anderen Partien wurden roh untersucht. Die Ergebnisse dieser Untersuchung wurden folgenderweise zusammengefasst. 1) In 250 Rhodeus lanceolata wurden sammt 54796 Metazerkarien aufgefunden, die in 14 folgenden Arten eingeteilt wurden, d.h. 1. Sog. Hasegawa'sche neue Art von Stammnosma. 2. Stanunuosoma armatum. 3. Exorchis oviformis. 4. Exorchis (Pseudexorchis) major. 5. Clonorchis sinensis. 6. Metagonimus takahashii. 7. Echinochasmus japonicus. 8. Echinochasmus perfoliatus. 9. sog. Hasegawa'sches unklares Distomum a. 10. Sog. Hasegawa'sches unklares Distomum b. 11. Sog. Hasegawa'sches unklares Distomum c. 12. Cyatocotyle b Hasegawa. 13. Cyatocotyle c Hasegawa. 14. Asymphylodora tincae. Die Infektionsköffizienten waren im Allgemeinen kleiner zwischen Januar und Juni, während vom Juli bis Oktober sehr gross, besonders im September am grössten, und dann wieder kleiner in den nachfolgenden 2 Monaten. Über das Sterblichkeitsverhältnis von Metazerkarien fand der Verfasser- am kleinsten in der Mitte des Septembers und am grossten in 2 Monaten vom Ende Oktober bis Dezember. Die neu entwickelten Metazerkarien werden meist zwischen Juli und August gefun-den. 2) Jede art zeigt ihre jahrzeittiche Schwankungen von Infektionskoeffizfent der Metazerkarien, insbesonders die der Stammosoma Arten, so wie die Sterblichkeit, sehr eigentümlich ist, nämlich ihren lebenden Metazerkarien vermehren ganz plötzlich im August und September (am grössten im Ende September) und dann wieder schnell vermindern, während die Zahl der gestorbenen Metazerkarien ausserordentlich gross fast ein ganzes Jahr hindurch, besonders kurz vor und nach der Vermehrung der lebenden Metazerkarien sind. 3) Der Infektionskoeffizient von Clonorchis sinensis ist gross zwischen dem Ende August und Oktober, sondern dagegen klein in den nachfolgenden 2 Monaten und vom Januar bis Juli. 4) Die übrigen Arten zeigen nicht so starken Schwankungen, aber auch vermehren meist im Sommern, und vermindern im Winter. 5) Es ist weiter erschlossen worden, dass für jahrzeitliche Schwankungen von Infektionskoeffizient der Metazerkarien die Sonnenlichtstrahlung und Wassertemperatur die gross Rolle spielt haben. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 122 3 2010 ラット出血性梗塞モデルにおけるエダラボンのneurovascular unit保護効果 195 197 EN Toru Yamashita Tatsushi Kamiya Kentaro Deguchi Toshiki Inaba Hanzhe Zhang Jingwei Shang Kazunori Miyazaki Aiji Ohtsuka Yasuo Katayama Koji Abe No potential conflict of interest relevant to this article was reported.

岡山大学埋蔵文化財調査研究センター Acta Medica Okayama 10 1996 津島岡大遺跡 7　―第11次調査―　（総合情報処理センター新営予定地） EN No potential conflict of interest relevant to this article was reported.

岡山大学埋蔵文化財調査研究センター Acta Medica Okayama 8 1995 津島岡大遺跡 5　―第8次調査―　（遺伝子実験施設・合併処理槽新営予定地） EN No potential conflict of interest relevant to this article was reported.

岡山大学埋蔵文化財調査研究センター Acta Medica Okayama 7 1994 津島岡大遺跡 4　―第5次調査―　（大学院自然科学研究科棟新営予定地） EN No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 57 1 2003 Enhancement of norepinephrine-induced transient contraction in aortic smooth muscle of diabetic mice. 45 48 EN Asaki Abe Chiaki Kawasoe Yasuhiro Kondo Katsunori Sato Article 10.18926/AMO/32840 <p>Changes in norepinephrine-induced transient contractions in Ca2+-deficient solution were investigated in the aortic smooth muscles of diabetic ALS (alloxan-induced diabetes susceptible) mice. The transient contractions in diabetic mice were significantly larger than those in normal mice. The longer incubation of the muscle preparations in Ca2+-deficient solution made the transient contractions smaller, probably due to the leakage and decrease in norepinephrine-releasable stored Ca2+. The rate of this reduction in contraction was slower in diabetic mice. These results suggest that the leakage of intracellular stored Ca2+ caused by extracellular Ca2+ deficiency is attenuated in diabetic mice, contributing to enhanced norepinephrine-induced transient contractions.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 55 1 2001 Reduction of ischemic damage by application of insulin-like growth factor-1 in rat brain after transient ischemia. 25 30 EN Jiang Ming Wang Takeshi Hayashi Wen Ri Zhang Feng Li Masanori Iwai Koji Abe Article 10.18926/AMO/32033 <p>In order to investigate a possible effect of insulin-like growth factor-1 (IGF-1) on ischemic brain injury, IGF-1 was applied topically on the brain surface of reperfused rat brain after 60 min of transient middle cerebral artery occlusion. In contrast to the cases treated with vehicle, the infarct volume was greatly reduced at 24 h of reperfusion by the treatment with IGF-1. Immunohistochemical analysis in the middle cerebral artery territory showed that Caspase-3 staining was markedly reduced in the cases with IGF-1 treatment, but 72-kDa heat shock protein staining remained almost unchanged. The present results suggest that treatment with IGF-1 exerts a significant effect on ameliorating brain injury after transient focal brain ischemia. Moreover, this effect is greatly associated with the reduction of Caspase-3 staining, but is only minimally associated with a decreasd stress response at the cellular level.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 52 4 1998 Evaluation of Rheumatoid Arthritis Using a Scoring System Devised from Magnetic Resonance Imaging of Rheumatoid Knees 211 224 EN Kazuhiro Takeuchi Hajime Inoue Yoshiki Yokoyama Masuo Senda Yusuke Ota Nobuhiro Abe Keiichiro Nishida Article 10.18926/AMO/31296 <p>We studied the magnetic resonance imaging (MRI) of 120 knees in 86 rheumatoid arthritis (RA) patients and of 14 unaffected knees in 12 control cases. We also developed a scoring system as a quantitative analysis method. We divided the MRI into 10 items, and classified the severity of the symptoms into 4 grades (score 0 to 3). The average total score increased according to the radiographic grade. Soft tissue lesions were clearly detected, even in the early stages of RA. Items such as synovial proliferation showed a high score even in the early stages, suggesting that it was the initial symptom of RA. The score also showed a correlation with the inflammatory signs. These results suggest that this scoring system is very sensitive and yields a good reflection of RA activity. We demonstrated that this system is simple and convenient for routine diagnostic use. We further demonstrated that it is useful for following the advancement of RA and for evaluating the response to treatment.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 62 3 2008 Novel magnetic resonance imaging evaluation for valgus instability of the knee caused by medial collateral ligament injury 185 191 EN Hisanori Ikuma Nobuhiro Abe Youichiro Uchida Takayuki Furumatsu Kazuo Fujiwara Keiichiro Nishida Toshifumi Ozaki Original Article 10.18926/AMO/30974 <p>Instability of the knee after the medial collateral ligament (MCL) injury is usually assessed with the manual valgus stress test, even though, in recent years, it has become possible to apply magnetic resonance imaging (MRI) to the assessment of the damage of the ligament. The valgus instability of 24 patients (12 isolated injuries and 12 multiple ligament injuries) who suffered MCL injury between 1993 and 1998 was evaluated with the Hughston and Eilers classification, which involves radiographic assessment under manual valgus stress to the injured knees. We developed a novel system for classifying the degree of injury to the MCL by calculating the percentage of injured area based on MRI and investigated the relationship between this novel MRI classification and the magnitude of valgus instability by the Hughston and Eilers classification. There was a significant correlation between the 2 classifications (p=0.0006). On the other hand, the results using other MRI based classification systems, such as the Mink and Deutsch classificaiton and the Petermann classification, were not correlated with the findings by the Hughston and Eilers classification in these cases (p0.05). Since MRI is capable of assessing the injured ligament in clinical practice, this novel classification system would be useful for evaluating the stability of the knee and choosing an appropriate treatment following MCL injury.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 60 3 2006 Decreased levels of insulin-like growth factor-1 and vascular endothelial growth factor relevant to the ossification disturbance in femoral heads spontaneous hypertensive rats. 141 148 EN Takamitsu Komiyama Keiichiro Nishida Masanori Yorimitsu Hideyuki Doi Shinichi Miyazawa Ai Kitamura Aki Yoshida Yoshihisa Nasu Nobuhiro Abe Toshifumi Ozaki Article 10.18926/AMO/30749 Ossification disturbance in femoral head reportedly is seen in the Spontaneously Hypertensive rats (SHR) between ages of 10 and 20 weeks. We investigated serum and tissue levels of insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) in SHR relevant to the ossification disturbance and osteonecrosis of the femoral head. Serum levels of IGF-1 and VEGF were significantly lower in SHR than in Wistar Kyoto rats (WKY) at weeks 5, 10, 15 and 20 (p&#60;0.005). The incidence of histological ossification disturbance of the femoral head was higher in SHR (59%) than in WKY (40%) at week 20. Lower serum and local levels of VEGF in SHR appeared to be related to the incomplete ossification of the femoral heads. Immunohistochemical study showed significantly lower numbers of IGF-1 and VEGF positive chondrocytes in the femoral epiphyseal cartilage of SHR than in those of WKY at weeks 10, 15 and 20. Our results suggest that local and/or systemic levels of IGF-1 and VEGF between ages of 5 and 20 weeks might play roles in the pathogenesis of ossifi cation disturbance of the femoral head in SHR. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 50 2 1996 Femoral neck fracture following avascular necrosis of the femoral head. 111 117 EN Masaaki Usui Hajime Inoue Shigehumi Yukihiro Nobuhiro Abe Article 10.18926/AMO/30487 <p>&#60;P&#62;Four cases of femoral neck fracture following avascular necrosis of the femoral head were studied histologically. All four patients were women who had received steroid therapy, three of them for systemic lupus erythematosus and the other for idiopathic thrombocytopenic purpura. Two types of fracture were found according to the site and the mechanism of fracture. One was at the junction between the necrotic bone and the repairing bone, and it can thus be regarded as a stress fracture. The other type of fracture commenced at the superior portion of the junction between the femoral head and neck, which was weak due to the repair reaction. The fracture line extended to the inferior cortex of the femoral neck, as often occurs in the elderly. In one patient, the femoral neck fracture was the first sign of avascular necrosis of the femoral head. &#60;/P&#62;</p> No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 122 1 2010 DNA 損傷センサーATMキナーゼとChk2はＣ型肝炎ウイルスのRNA複製に必要である 9 16 EN Yasuo Ariumi Misao Kuroki Hiromichi Dansako Kenichi Abe Masanori Ikeda Takaji Wakita Nobuyuki Kato No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 33 1 1998 Rigid-Plastic Deformation of Inhomogeneous Material with Elliptic Inclusions Sliding along Boundary 5 17 EN Takeji Abe 10.18926/19606 The influence of the slip between the inclusion and the matrix during the plastic deformation of inhomogeneous material with elliptic inclusions is investigated. The material is assumed to be rigid-plastic. The boundary slip region is modeled by assuming lower yield stress for the thin boundary region than those of the inclusion and the matrix. The rigid-plastic finite element method is used for the numerical calculation under the plane strain condition. The effects of the aspect ratio of the inclusion, the yield stress of the boundary region, and the volume fraction of the inclusion on the deformation mode are studied. The patterns of the strain concentration and the averaged flow stress of the inhomogeneous material are also discussed. The results may be helpful for understanding creep or superplastic deformation of metals with inclusions. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 84 3-4 1972 ネコの視床後腹側核の視床内結合に関する実験解剖学的研究 11 23 EN Kumashige Abe The present study was undertaken to elucidate the intrathalamic fiber connections of the posterior ventral nuclei of the thalamus. Localized stereotaxic lesions were placed in various parts of these nuclei in 13 cats, and the ensuing terminal degeneration in the dorsal thalamic nuclei were studied by the Nauta and Gygax method. Within the posterior ventral nuclei, the posteromedial and posterolateral ventral nuclei are diffferentiated. The posteromedial ventral nucleus is further divided into the medial parvocellular and the lateral main parts. The posterior ventral nuclei have intrathalamic connections to the surrounding thalamic nuclei, in addition to cortical projections. Regarding the intrathalamic connections from different parts of the posterior ventral nuclei some differences in termination are noted. The medial part of the posteromedial ventral nucleus, regarded as a thalamic relay station in the gustatory paths, sends fibers profusely to the intralaminar nuclei in a wide sense, including the centre median and parafascicular nuclei, and are connected across the midline with the paracentral and lateral central nuclei and the medial part of the posteromedial ventral nucleus on the opposite side. It should be mentioned that the rhomboid and medial ventral nuclei are not only pierced by decussating fibers, but also receive terminal fiders from the medial part of the posteromedial ventral nucleus. This part sends a limited number of fibers to the lateral part of the posteromedial ventral nucleus and the other ventral nuclei, including the submedial nucleus, as well as to the dorsal medial, posterior lateral and suprageniculate nuclei, but gives off no fibers to the medial and lateral geniculate bodies or the medial and inferior pulvinar nuclei. The lateral main part of the posteromedial ventral nucleus and the posterolateral ventral nucleus are considered to be thalamic relay centers for somatic sensibility. The former sends fibers to the other ventral nuclei, viz. the posterolateral ventral, lateral ventral, medial ventral and submedial nuclei. It also gives off fibers to the intralaminar nuclei in a wide sense, the lateral part of the dorsal medial nucleus and the posterior lateral, suprageniculate and medial pulvinar nuclei, but send scarcely any fibers to the medial and lateral geniculate bodies. It sends no decussating fibers to the contralateral dorsal thalamus. The dorsolateral part of the posterolateral ventral nucleus sends fibers to the posterior lateral, inferior pulvinar, suprageniculate nuclei and the lateral geniculate body, particularly its ventral nucleus. It also gives off fibers to the lateral part of the posteromedial ventral nucleus and the lateral ventral nucleus, but sends no fibers to the medial part of the posteromedial ventral nucleus or the dorsal medial, medial pulvinar, submedial and medial ventral nuclei. In addition, it gives rise to neither decussating fibers to the contralateral side nor terminal fibers to the midline nuclei. The dorsolateral part sends only few fibers to the intralaminar nuclei in a wide sense. The ventromedial part of the posterolateral ventral nucleus sends more abundant fibers to the intralaminar nuclei in a wide sense and the posteromedial ventral, medial ventral and submedial nuclei than does the dorsolateral part, but gives off a lesser amount of fibers to the lateral geniculate body and the inferior pulvinar and lateral ventral nuclei. It sends fibers to the posterior lateral and suprageniculate nuclei, and only few fibers to the medial geniculate and dorsal medial nuclei which receive no fibers from the dorsolateral part. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 121 3 2009 膵癌診療ガイドライン―内科治療の総論について― 195 198 EN Ken Hirao Hirofumi Kawamoto Kazuhide Yamamoto No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2009 Eco-physiological studies on the migration limited in freshwater areas and spawning of kissing loach: Adaptations of teleost fishes to floodplain environments EN Tsukasa Abe No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2009 プラント制御支援のための人間モデルと知識獲得に関する基礎研究 EN Yoshihiro Abe No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2009 Cell culture-adaptive NS3 mutations required for the robust replication of genome-length hepatitis C virus RNA EN Kenichi Abe No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 25 1 1990 The Structure of Interregional Migration in Japanese Regions : An Application of Multidimensional Scaling 89 98 EN Hirofumi Abe 10.18926/15496 Multidimensional scaling (MDS) has been used in a wide variety of research fields; psychology, political science, anthropology, marketing research, urban and regional planning, and so on. In practical terms, MDS is a statistical method to make a picture of the information in the data. It enables us to examine the "hidden structure" of a set of data. When the set of data is large, MDS is extremely useful, since it is easier and more informative to look at a picture than the data themselves. In this paper, MDS is applied to the interregional migration data of Japanese regions for the years 1960-85. Findings show that the two-dimensional configuration of regions estimated by MDS generally corresponds with the geographical locations of regions, and the structure of interregional migration was very stable over the study years 1960-85. It is also suggested that MDS is a useful tool to identify the relationships between regions using the spatial interaction data. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 24 1 1989 Trends in the Regional Structure of Manufacturing Industries in Japan 115 133 EN Hirofumi Abe 10.18926/15485 The rapid economic growth of Japan in the postwar period has brought about the over-concentration of activities in a few large cities, and local regions have been losing their economic vitality due to the regional differentials and the population loss. Regional development planning in Japan has sought to achieve a balanced growth of the nation through the development of industries in local regions. This paper aims to examine the regional structure of manufacturing industries in the postwar period and to identify its current problems. Three methods, namely the analysis of coefficient of variation, the rateshare analysis and the shift-share analysis are applied using employment data of manufacturing industries for the years 1955 to 1985. Findings show that while the employment of manufacturing industries has been markedly decentralized from metropolitan to local regions, the disparities in growth rates still exist among regions. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 27 1 1992 The Impact of JR Seto Ohashi Line on Residential Land Value 81 92 EN Hirofumi Abe 10.18926/15396 This paper aims to examine the impact of JR (Japan Railways) Seto Ohashi Line on residential land value. First, the study examines the trends in land value in the area along JR Seto Ohashi Line by applying the area comparison method. The method estimates the effect of JR Seto Ohashi Line on residential land value by comparing land values between the study area and the Okayama Metropolitan Area. Second, the property value method is applied to measure the effect of railroad construction. The effect is estimated with a residential land-value regression, which is calibrated using land value data along the Seto Ohashi Line. Finally, the results are compared with the empirical studies in the Greater Tokyo Region, and various features of the impact of railroad construction on land value are identified. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 35 1-2 2001 Ultra-Micro Hardness Testing and Microscopic Deformationof Polycrystalline Aluminum 9 19 EN Takeji Abe Tomoaki Tsuboi 10.18926/15346 The evaluation of microscopic inhomogeneity of polycrystalline aluminum is performed by measuring the hardness in respective grains. The recently developed ultra-micro hardness tester is used and the effects of the test pattern, the indentation load and the indenting velocity are examined. Then, the relationship between the increase in the hardness caused by the work hardening and the deformation of respective grains are statistically investigated. The hardness testing mode in which the initial load is applied before the onset of measurement gives more stable results than the testing mode without the initial load. The test condition with the indentation load of 9.8mN and the indentation velocity of 0.2 μm/sec seems to be optimum and gives the least dispersion of the measured values in grains. It is shown that the hardness values of respective grains in polycrystalline aluminum as well as their dispersion increase with the applied plastic strain. Discussion is made on the microscopic deformation behavior of polycrystalline aluminum. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 35 1-2 2001 Microscopic Observation of Plastic Deformation of Polycrystalline Aluminum by Laser Scanning Microscope 1 8 EN Takeji Abe Ichiro Shimizu 10.18926/15344 Free surface of polycrystalline metal becomes roughened after plastic deformation. The surface roughening is closely related to the inhomogeneity of polycrystalline metals, that is, to the inhomogeneous plastic deformation of respective grains. In the present study, inhomogeneous deformation on the free surface of polycrystalline aluminum specimen during uniaxial tension is studied. The inhomogeneous deformation of grains in the central area of the free surface of specimen is observed by the laser scanning microscope, while the inhomogeneous deformation perpendicular to the surface is studied by the laser scanning microscope as well as the stylus measuring instrument. It is shown that the surface roughness and the strain of respective grains increase with the applied strain. Discussions are made on the change in the surface roughness, the strain in each grain and the slip-line angles with the applied strain. No potential conflict of interest relevant to this article was reported.

岡山大学医療技術短期大学部 Acta Medica Okayama 0917-4494 8 2 1998 Molecular typing of enterohemorrhagic Escherichia coli O157 : H7 isolates derived from an outbreak in Okayama, Japan in 1997 by pulsed-field gel electrophoresis 91 95 EN Kanji Miyamoto Kazunari Sakamoto Masami Niiya Jing Chen Eriko Abe Yuka Okazaki Kiyoko Shirai Noriko Goda 10.18926/15257 Thirteen enterohemorrhagic Escherichia coli O157 : H7 (EHEC) isolates derived from the patients of an outbreak in the R-hospital in Okayama Japan and one isolated from the ingredients of Japanese noodles in June 1997 were analyzed by molecular typing using pulsed-field gel electrophoresis (PFGE). The PFGE patterns of the patients were almost the same as the patterns of the Japanese noodle ingredients. Therefore, the EHEC O157 : H7 derived from the food was considered to have caused the outbreak in the R-hospital. The molecular typing of isolates from the patients and the Japanese noodle ingredients was almost the same as that of isolates from outbreaks in Hiroshima and Fukuoka prefectures classified as type Ia in 1996 by PFGE analysis. These results indicate that EHEC O157 : H7 strains with a similar PFGE type Ia pattern have already spread throughout western Japan since last year. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 121 1 2009 イレウス症状で発症した小腸アニサキス症の１例 25 27 EN Sayaka Fujii Manabu Nishie Ryousuke Hamano Naoyuki Tokunaga Yousuke Tsunemitsu Shinya Ootsuka Kazuya Miyoshi Masahiko Takahashi Masaru Inagaki Toshihide Oosaki Hiromi Iwagaki We report a surgical case of intestinal anisakiasis in which we identified a complete larva. A 48-year-old man complaining of epigastralgia after eating roasted mackerel was admitted to the hospital with a diagnosis of ileus with peritonitis. Abdominal CT showed dilatation and partial thickening of the small intestine. An emergency operation was carried out. On laparotomy, severe stricture of the jejunum was revealed. The affected intestine was resected. A larva whose head was invading the mucosa was found in the resected portion of the jejunum, and we diagnosed the case as intestinal anisakiasis. No potential conflict of interest relevant to this article was reported.

岡山大学保健環境センター環境安全部門 Acta Medica Okayama 0917-1533 28 2006 東アジアの季節サイクルや日々の気象に注目した最終氷期頃の気候環境の理解へ向けて 17 27 EN Kuranoshin Kato Shoichiro Ikeda Kana Abe Regional climate system in East Asia shows the characteristic seasonal cycle affected by the Asian monsoon with various types of its sub-systems. The seasonal cycle there is also related greatly to behaviors of the frontal zones which are the boundaries of these sub-systems. Since the variation of global-scale environment such as the global warming influences on each monsoon sub-system in rather different manner, it is necessary to understand the joint effects of these subsystems, in order to predict the regional climate change in East Asia in the global warming. In such research, it would be also useful to examine the features in the ice age, as an opposite extreme situation against the global warming. Thus the present paper will discuss some viewpoints in investigating the regional climate in the Last Glacial Maximum with attention to the seasonal cycle and daily meteorological systems. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 103 5-6 1991 エンドトキシンが体内亜鉛代謝に及ぼす影響に関する実験的研究 505 515 EN Masaki Matsumi The effect of endotoxin administration on zinc metabolism was studied in rats. In the endotoxin-treated rats, serum zinc concentration was significantly reduced as compared to saline-treated rats (control group). On the other hand, hepatic zinc concentration was significantly increased after endotoxin administration as compared to the control group. However, the zinc concentrations of the liver cell components showed slightly dissimilarity. In the mitochondria and cytsol, the concentration increased significantly after endotoxin administration as compared to the control group, whereas no change was observed in the microsomes. Furthermore, we have examined whether the increase of the zinc level in the cytosol of the liver is associated with zinc-binding protein metallothioneins (MTs) or not. MTs also increased significantly after endotoxin administration. Furthermore hepatic MTs were analyzed for MT isoforms. In the endotoxin-treated MT-II was the major Iso-MT. Judging from these results and some other published reports, the role of zinc metabolism in endotoxemia is proposed to be as follows. In endotoxemia the serum zinc concentration is reduced and as a result the production of superoxide by polymorphonuclear leukocytes is increased as zinc has an inhibitory effect on it. This free radical helps the host against the organism. On the other hand zinc accumulation in the liver following endotoxin administration increases the activity of the zinc binding-enzyme and also stabilizes the plasma membrane. MTs induced by endotoxin protect the host from the harmful effects of the free radical in the host by its scavenging action. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 103 5-6 1991 慢性膵炎の経過と予後に関する研究 第1編 診断時の状態と膵管像，膵外分泌機能，耐糖能の経時的変化について 463 472 EN Hirofumi Miyake To clarify the chief complaints, pancreatograms, pancreatic exocrine function and glucose tolerance at diagnosis and their serial changes in chronic pancreatitis (CP), 112 patients with alcoholic CP, nine with biliary CP and 49 with idiopathic CP were studied. The following conclusions were obrained. Seventy-seven patients with alcoholic CP, nine with biliary CP and 22 with idiopahtic CP had presented with recurrent abdominal pain for more than one year before the time of diagnosis. Chief complaints consisted of abdominal pain , diabetes mellitus and others. Proportion of patients with abdominal pain was significantly higher in alcoholic CP than in idiopathic CP. Elderly patients with CP presented with abdominal pain less frequently than non-elderly patients. These findings indicate that chronic pancreatitis should be considered when diagnosing and treating diabetics and the elderly. Patients with alcoholic CP were significantly younger than those with nonalcoholic CP at diagnosis. Sex distribution showed male predominance in alcoholic CP and female predominance in nonalcoholic CP. Calcification in the pancreas was detected more frequently in alcoholic CP than in nonalcoholic CP. The number of patients with CP increased in more recent years. Alcoholic CP showed more severe damage of the pancreas than nonalcoholic CP at the time of diagnosis. No differences between alcoholic CP and nonalcoholic CP were found in the frequency of the progressive changes in pancreatograms. Deteriorative changes in pancreatic exocrine function were not related with etiological category, but improvement was observed frequently in nonalcoholic CP. The deterioration of glucose tolerance was not related with etiological category, drinking habit and pain relief. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 102 1-2 1990 Pringle 法急性肝流入血行遮断の肺血管外水分量におよぼす影響　第1編　肺血管外水分量の増加とその成因を中心として 63 76 EN Nobuji Yokoyama To elucidate the effect of total hepatic ischemia on pulmonary organs, extravascular lung water (EVLW) was experimentally measured using a modified double indicator dilution method before and after interruption of the hepatic blood flow using Pringle's maneuver. The follow-ing results were obtained : 1) EVLW was significantlly increased more than one hour after temporary total hepatic ischemia. 2) Temporary hypotension resulted in little increase of EVLW by removing and replacing some blood volume through the femoral artery. 3) Pumonary interstitial edema was histologically and maroscopically observed in the Pringle's maneuver group. 4) Marked metabolic acidosis and elevation of serum transaminase were revealed after temporary hepatic ischemia. These findings auggest that pulmonary interstitial edema may result from sfter temporary total hepatic ischemia by Pringle's maneuver and the changes of EVLW are caused by increased permeability due to liver injury, metabolic acidosis and portal congestion. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 102 1-2 1990 核 DNA 量による乳癌の悪性度判定ならびに内分泌療法の作用機序の研究―Flow cytometry による解析― 37 49 EN Hiroyoshi Doihara To evaluate for primary breast cancer, flow cytometric DNA analysis has been performed on 105 paraffin-embedded tissues. The S-phase fraction and proliferation index correlated significantly with clincopathological factors, sunh as n-number, tumor size, histological stage and hormone receptors. However, there was no correlation between the level of ploidy and the clinicopathological factors. DNA analysis using flow cytometry was found to be useful for the estimation of prognosis and evaluation of malignancy of breast cancer. The effect of medroxyprogesterone acetate (MPA) on primary breast cancer cell kinetics was investigated by flow cytometry. Nuclear DNA contents were measured in 67 cases. MPA, 1,200mg/day, was orally administered for two weeks in 12 cases (MPA group) and the remain-ing cases (n-MPA group) served as the controls, until the day before operatopn. The DNA histograms were compared between both groups. The mean percentage of G0 + G1 phase was higher and that of S-phase and G2 + M phase, lower, in the MPA group than in the n-MPA group. Especially in estorogen receptor-positive and premenopausal cases, significant differ-ences were present between both groups. These results suggest that MPA could inhibit DNA synthesis with a delay of the cell cycle progression in human breast cancer. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 103 1-2 1991 脳血管攣縮の発生機序と治療に関する実験的研究 第2編 実験的遅発性脳血管攣縮に対する PGI2 analogue, Thromboxane A2 合成酵素阻害剤, Ca 拮抗剤の効果 183 197 EN Mototsugu Motoki The effects of a PGI2 analogue (OP-41483), a thromboxane A2 synthetase inhibitor (OKY-046) and a Ca blocker (nifedipine) on the diameter of constricted basilar arteries and on the regional cerebral blood flow (r-CBF) in the brain stem were investigated in the cat delayed spasm model. The experiment was performed three days (72 hours) after artificial subarachnoid hemorrhage. The basilar artery was exposed transclivally, and more advanced vasospasm was produced by topical application of a lysed erythrocyte solution for 5 to 6 hours which domonstrated no more vascular dilatation even by topical application of papaverine hydrochloride (0.01mg/ml). In the delayed spasm model, the intravenous administration of neither OP-41483 (8μg/kg), OKY-046 (60mg/kg) nor nifedipine (0.003mg/kg) affected the vascular diameter. OP-41483 increased r-CBF in the brain stem in 3, and nifedipine increased it in 4 out of the 5 studied delayed spasm models, whereas OKY-046 never increased r-CBF (n=5). There was no significant difference in the amount of fatty acids including arachidonic acid between normal and constricted arteries. This study suggested that thromboxane A2 is not the major factor of cerebral vasospasm and OKY-046 might not be effective on vascular diameter or r-CBF at the late spasm stage. However, the PGI2 analogue (OP-41483) and Ca blocker (nifedipine) may be effective in increasing r-CBF even at the late spasm stage. No potential conflict of interest relevant to this article was reported.

岡山大学農学部 Acta Medica Okayama 0474-0254　 98 1 2009 低アレルギー発症性が言及されている鶏卵の機能特性に関する動物実験 31 37 EN Kumiko Nagato Asaki Abe Kiyoaki Narabara Yasuhiro Kondo Functional features concerned with low proallergic natures were examined using an allergy-inducible rat strain (Brown Norway rat; BN rat) on hen's eggs which have been empirically mentioned as hypoallergenic for patients suffering from food allergies (experimental eggs). BN rats were fed on feed containing whole experimental eggs (feed E) and whole normal eggs (control feed, feed C). The densities of immunoglobulin E (IgE)-positive cells, have reported to be IgE-bearing mast cells, in the jejunum and ileum of BN rats fed on experimental-egg-containing feed were lower than those of BN rats fed on normal-egg-containing feed. The number of blood eosinophils was also lower in BN rats fed on feed E. Serum IgE levels were no different between BN rats fed on feed E and feed C. These results indicate that the low proallergic nature of hen's eggs studied in the present study is due to the dereased ability of experimental eggs to facilitate the proliferation and induction of mast cells in the intestinal tissue. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 103 1-2 1991 虚血性腎傷害による亜鉛代謝と腎内メタロチオネインの変動に関する実験的研究 161 171 EN Shun-ichi Mizukawa The renal and hepatic metallothionein (MT) and serum zinc levels were studied in rats following renal ischemia, to clarify the effects of renal damage on the zinc metabolism. The serum zinc concentration began to decrease on the 4th day in the bilateral renal ischemic rat. The accumulation of hepatic MT was stimulated by sham operation and was augmented furthermore by renal ischemic damage. The renal MT level increased gradually and reached the maximum on the 3rd day in the bilateral renal ischemic rat. The MT level in the injured kidney was higher than that in the intact kidney in the unilateral renal ischemic rat. These results suggested that the mechanism of MT synthesis in the kidney was different from that in the liver, and that some local factor might induce MT in the injured kidney. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 5-6 1992 LHRH 負荷試験による小児期のゴナドトロピン分泌予備能に関する検討ー高精度 LH, FSH 測定法 (IRMA 法) による分泌動態の解析ー 581 590 EN Joji Higuchi To investigate the age-related changes in the pituitary responsiveness to luteinizing hormone-releasing hormone (LH-RH), the consentrations of serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured before and after LH-RH administra-tion using the highly sensitive immunoradiometric assay (IRMA) in 283 normal children (161 males and 77 females) between 4 and 14 years old and in 22 patients (18 males and 4 females) with pituitary dwarfism. Then, the area of response above the basal level [integrated response(Σ)] of LH and FSH during 60 minutes after LH-RH injection was calculated to evaluate the pituitary response to LH-RH. The integrated LH responses progressively increased in the boys from 8 years of age and in the girls from 6 years of age, and they continued to increase up to 14 years of age. The integrated FSH response showed a significant decrease in all grups in the girls, but did not show any change in the boys. In patients with pituitary dwarfism who were subsequently found to be gonadotropin deficient, the level of Σ LH60 was low (below-2SD) It is concluded that integrated responses of gonadotropins, especially LH, to LH-RH are useful to evaluate the maturation of the hypothalamic-pituitary-gonadal axis, and that incre-ment of LH responsiveness to LH-RH already begins before the onset of puberty. The peak appearance time of gonadotropins after LH-RH is also important in the assessment of the maturation of the hypothalamic-pituitary-gonadal axis because FSH reached its peak carlier in the pubertal group than in the prepubertal group. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 5-6 1992 僧帽弁膜症患者の心機能と栄養障害に関する検討 549 559 EN Itsuhiro Miyazaki To examine the influence of cardiac function on the nutriture, operated cases of mitral valve disease were evaluated for preoperative cardiac function by morbid type and were examined for the influence of cardiac function on the pre- and post-operative nutriture. The findings revealed that the hypofunctional group showed no difference in visceral protein index from the normal group preoperatively, and showed significant decreases in % IBW, % TSF, and CHI, indexes of fat stores and skeletal muscle mass. The hypofunctional group also showed low value of PPD intracutaneous reaction, an index of the immunological status. The early postoperative nutriture of the hypofunctional group showed changes similar to those in the normal group and was less influenced by the preoperative cardiac function. These findings suggest that the cardiac function influences the body composition and immunological status and that somatometry and PPD intracutaneous reaction are useful for the nutritional assessment of heart diseases. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 5-6 1992 超音波連続波照射の安全性に関する研究 539 548 EN Junichirou Kawai Rat fetuses were extra-abdominaly exposed to 2 MHz continuous wave ultrasound, with 1.5 or 2.5W/c㎡ of spatial average (SATA) intensity, for 15 min at 7.5 to 11.5 days of pregnancy. Fetal anomalies were observed only in the groups exposed to 2.5 and 1.5W/c㎡ at 9.5 days of pregnancy but its occurrence was not statistically significant. Intrauterine fetal deaths were most prevalent in the group exposed to 2.5W/c㎡ at 9.5 days of pregnancy, followed by the group exposed to 2.5W/cm2 at 10.5 and 7.5 days of pregnancy. At three months after birth, the behavior (open field test), the learning ability (avoiding study and single straight pathway test) and the fertility of these exposed rats were compared with those in non-exposed rats. In the avoiding study, there was statistically less avoidability in the group exposed to 2.5W/c㎡ at 9.5 days of pregnancy than the non-exposed group. In the other tests, no significant differences could be found between the exposed group and non-exposed group. These findings indicated that rat fetuses at 9.5 days of pregnancy are most senstive to continuous wave ultrasound exposure followed by fetuses at 10.5 or 7.5 days of pregnancy. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 103 1-2 1991 賦活凝固時間におよぼす急性呼吸性 pH 変化の影響に関する実験的研究 95 103 EN Kozo Seto The effects of acute respiratory acidosis and alkalosis on the activated coagulation time (ACT) of both pre-heparinized and post-heparinized blood samples were studied in adult mongrel dogs. The ACT of pre-heparinized samples, compared with the ACT at a normal pH, was significantly shortened with the progression of acidosis. The correlation coefficient between the ACT of pre-heparinized samples and the pH values during acidosis was 0.55 (p<0.01). During alkalosis, however, the ACT of pre-heparinized samples showed no significant changes. On the other hand, the ACT of post-heparinized samples, compared with the ACT at a normal pH, showed significant prolongation with the progression of both acidosis and aklalosis. The correlation coefficient between the ACT of post-heparinized samples and the pH values was -0.74 (p<0.001) during acidosis, and was 0.55 (p<0.01) during alkalosis. These results indicate that, although the mechanism of the alteration of ATC due to the acute respiratory pH changes seemed to be multifactorial, the ACT in the presence of pH abnormality does not reflect the actual blood concentration of heparin correctly. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 5-6 1992 子宮体癌に対する経腟走査超音波断層法とMRIの有用性について―筋層浸潤と頚部浸潤の評価― 489 499 EN Eisuke Yoshihara Between October, 1988 and March, 1991, twenty-mine patients with endometrial carcinoma bad both transvaginal ultrasonography (TVUS) and magnetic resonance imaging (MRI) performed following hysterectomy at the Departmetn of Gynecology and Obstetrics, Okayama University Medical School. The findings were compared with the pathological findings to determine the usefulness of each method. The sensitivity of dectecthing myometrial invasion was 100% by TVUS and 96% by MRI. The accuracy was 86% by each method. The depth of myometrial invasion was classified into 3 degrees [no myometrial invasion, superficial invasion (≤1/2), deep invasion (>1/2)]. The correct diagnostic rate was 86% by TVUS and MRI. The minimum width and the minimum/maximum width ratio of the intact myometrium obtained by each method in the pathological deep invasion group were significantly lower than those obtained in the other two groups (p<0.01). The sensitivity, the accuracy and the specificity of detecting cervical invasion were 89%, 93% and 95% by both methods. There was no difference between TVUS and MRI for diagnosing myometrial and cerical invasion of endometrial carcinoma. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 5-6 1992 腎動脈性高血圧に推骨動脈―後下小脳動脈分岐部巨大動脈瘤を合併した線維筋性異形成の一例 483 487 EN Hiroshi Nakagawa Shozo Kusachi Takefumi Oka Norio Urabe Kunio Nogami Masao Takemoto Naoya Morishita Kimihito Inoue Takao Tsuji Susumu Tomita A 27-year-old man was admitted with symptoms of hypertension and headache. His soft palate and uvula were deviated to the right. The left side of his tongue was atrophic with fasciculation. Plasma renin activity, plasma angiotensin-I and aldosteron levels were elevated. Renal arteriography revealed membranous-stenosis with poststenotic dilation at the mid and peripheral portion of the renal artery, which was consistent with the findings of fibromus-cular dysplasia (FMD). Large aneurysm at the bifucation of the vertebral artery to postero-inferior cerebellar artery was observed by cerebral arteriography. The patient was treated with medication for renal hypertension. Percutaneous embolization of the aneurysm was performed. In conclusion, the present case had a giant cerebral aneurysm, located at a rare portion and was diagnosed before its rupture. Examination of the cerebral artery was essential in renal FMD. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 5-6 1992 エンドトキシンおよび亜鉛投与ラットにおける腎メタロチオネインの誘導に関する実験的研究 457 469 EN Yoshizumi Kanai Metallothionein (MT) induction in the rat kidneys by endotoxin and zinc was investigated at the MT-protein level and the MT-mRNA level. The MT-mRNA level increased 3-6 hr after endotoxin administration, which suggested that MT was not transported from an other organ, but was de novo synthesized. Two MT-protein isoforms, MT-Ⅰ and MT-Ⅱ, were induced by administration of both endotoxin and zinc. The maximum levels of the proteins were seen 9 hr after administration of endotoxin and zinc. The span life of the renal MT induced by zinc was shorter than that of the liver MT induced by zinc. The MT-Ⅱ isoform was predominantly induced by both inducers, endotoxin and zinc, and the ratios of MT-Ⅱ to MT-Ⅰ were relatively constant. The finding that MT-Ⅰ and MT-Ⅱ were almost equally induced by zinc in the liver indicate that MT induction is controlled by an organ-specific system. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 103 7-8 1991 NIH 3T3 細胞の温熱耐性に対するケルセチンの作用　第1編　細胞の生存率からみたケルセチンの作用 973 981 EN Masahiro Kuroda Yoshio Hiraki Shouji Kawasaki The inhibition of thermotolerance development by quercetin was examined in NIH 3T3 cells. The cytotoxicity of quercetin increased with the increase in the concentration (10,100μg/ml) and duration (12,48,72 hours) of treatment. The cell killing effect of heat was not enhanced by quercetin (10μg/ml) itself. Quercetin (10μg/ml) inhibited the proliferation of cells for about 72 hours. Quercetin (10μg/ml) delayed the development of thermotolerance, but did not decrease the degree of maximum thermotolerance. Quercetin (10μg/ml) exibited no effect on the decay of thermotolerance. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 3-4 1992 インターフェロン並びにインターフェロン誘発剤に関する基礎的・臨床的研究　第2編　急性非リンパ性白血病寛解期における β-Carboxyethylgermanium sesquioxide (Ge-132) の臨床効果 259 266 EN Mitsuhiro Fukumoto The clinieal of Ge-132 in the management of acute nonlymphocytic leukemia (ANLL) patients at remission phase were studied. Twenty-two ANLL patients with complete remission were randomized into Groups A and B. Patients in Group A were treated with the combianation with Ge-132 (2,250mg/day ; p. o daily) and intermittent-alternating chemotherapy 〔daunorubicin, vincristine, cytosine arabinoside and prednisolone (DVCP)/aclarubicin vincristine cytosine arabinoside and prednisolone (AVCP)〕and patients in Groyp B were treated with intermittent-alter nating chemotherapy (DVCP/AVCP) alone. Evaluable patients were 7 in Group A and 10 in Group B. Remission duration and survival time were not significantly different between Groups A and B. (median remission duration ; 5.7 month in Group A vs 8.1 month in Group B/median surival time ; 23.9month in Group A vs 18.3month in Group B) The rates of second remission in relapsed cases were not significantly different between Groups A and B.〔2 of 7,(28.6%) in Group A vs 3 of 10,(30.0%) in B〕Ge-132 did not accelerate the recovery from myelosuppression after intensification with the DVCP regimen. The incidence of liver damage and levels of serum GOT and GPT tended to be lower in Group A than in Group B. In this clinical study the incidence of liver damage tended to be lowere in patients treated with Ge-132. The liver damage which often develops during intensificantion chemotherapy, not only limits the chemotherapy but also causes adverse effects on the quality of life of the patient. In part 1 of this series, Ge-132 was reported to activate the neutrophil chemiluminescence. Ge-132 seems to be useful in the management of ANLL patients not only by the enhancement of the host defense system but also by the prevenation of liver damage. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 3-4 1992 インターフェロン並びにインターフェロン誘発剤に関する基礎的・臨床的研究　第1編　インターフェロン並びにインターフェロン誘発剤の好中球 Chemiluminescence に及ぼす影響 247 258 EN Mitsuhiro Fukumoto To evaluate one the effects of interferon (IFN) and its inducers on neutrophil functions neutrophil chemiluminescence (ChL) was assayed on 31 healthy individuals, nine patients treated with IFN-α (human lymphoblastoid interferon, 3×10(6)units/day i. m. daily) and 11 patients treated with Ge-132 (2,250mg/day p. o. daily). The base lines (BLs), peak levels (PLs) and times to PLs (PLs) of neutrophil ChL were examined before, one week and one month after the treatment. The direct effects of IFN-α, Ge-132 and OK-432 on neutrophil ChL were also evaluated by using an in vitro experimental system. PLs were significantly increased one week after the treatment with IFN-α or Ge-132. However, they were decreased to the pretreatment level one month after the treatment. In vitro experimental system IFN-α enhanced PLs of neutrophil ChL showing dose and time dependencies. On the other hand Ge-132 and OK-432 showed no direct effect on neutrophil ChL in vitro. These findings suggest that IFN-α and Ge-132 enhance the host defense mechanism by the activation of neutrophil functions, and also suggest that they have some benefits not only in the clinical management of cancer but also of chronic infection. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 11-12 1992 ANP 分泌―血行動態と特殊顆粒に関する検討 1135 1144 EN Hirotaka Asano To clarify factors affecting atrial natriuretic peptide (ANP) secretion, the relationship between blood ANP level and intracardiac pressure, and that between the number of atrial specific granules (ASG) in the right atrial auricle and ANP level were investigated in 21 patients undergoing extracorporeal circulation. In the atrial loaded group, the Group TR (Tricuspid regurgitation) served as right atrial load and Group M (Mitral valve disease) as left atrial load, ANP and the number of ASG were compared with those in the control group. Accordingly, the effect of atrial load on ANP secretion and the number of ASG were investigated. Moreover, ANP and the number of ASG in the atrial myolysis group {Group A f(atrial fibrillation)} were compared with those of the sinus rhythm group to determine effect of atrio-myolysis. The ANP level showed a positive correlation with left atrial pressure (r=0.820 p<0.01) and with left ventricular end-diastolic pressure (r=0.726 p<0.01), but no correlation with right atrial pressure nor ventricular pressure. The ANP level in Group M was significantly higher than other groups, but there was no significant difference compared with Group TR. Consequently, the left atrium and rihgt atrium were considered to have different effects on ANP secretion. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 1-2 1992 心臓弁膜症のMR画像診断支援システムの開発とその臨床応用に関する研究 187 194 EN Tomio Nakagawa MRI is a valuable tool for diagnosing heart disease today. The cardiac blood flow is determined by an MRI image analysis and expert system. Image data are taken by a TV camera and digitalized. After gray level thresholding and region segmentation, the boundary of the regurgitant flow region is precisely extracted. Using this expert system, a doctor can easily make an accurate diagnosis of the valvular heart disease. This method should prove useful for the diagnosis of various heart diseases. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 9-10 1992 乳癌サーモグラフｨ所見と予後の検討;サーモグラフｨにおける温度上昇と血管構築の変化 931 941 EN Masakazu Murakami The thermographic findings of 191 patients with Satges I-III breast cancer were retrospectively evaluated to determine the prognostic indicators of disease-free survival in both the whole study population and in each histological stage. The angioarchitecture of 75 breast cancer specimens was subsequently examined morphometrically using an immunohistochemical method, and was then compared with the extent of increase in the temperature at the tumor site. The extent of increase in the temperature was more closely related to the prognosis than was the thermal pattern. In stage II cancer (n=57), patients with lesions that showed a temperature increase > 1.5℃ had a poorer prognosis than the patients with hypothermic regions. (p<0.05). The range of skin temperature elevation at the tumor site correlated with the vascular changes in the skin above the tumor rather than with changes within or around the tumor in all of the patients. The increase in temperature above a tumor was concluded to be useful for assessing the prognosis and the grade of malignancy of breast cancer. The skin blood flow was also suggested to have the closest relationship with thermographic findings and the extent of the increase in blood flow to be a prognostic indicator for breast cancer. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 9-10 1992 肺癌における簡易式一時バイパス法を用いた大動脈合併切除の一例 923 929 EN Fumiyuki Inoue Yasuaki Kamikawa Yoshio Naomoto Akira Gouchi Kunzo Orita Takato Hata Masahiko Kuinose Hirofumi Nanba Gyou Taniguchi Left pneumonectomy and concomitant resection of the invaded aorta were performed by the simple temporary bypass method. The patient was a 59-year-old male with the chief complaint of left thoracic pain. The 57×43×35 mm tumor was in a region centering on segment 6 of the left lung and had infiltrated the descending aorta. It was diagnosed as T4NOMO, Stage IIIb. A bypass for blood flow was established between the aortic arch avobe the invasion and the left femoral artery, after ligation of the pulmonary artery and vein and closure of the left bronchial stump. Vascular blocking forceps were applied to the descending aorta above and below the tumor infiltration, and two thirds of the circumference of the invaded aortic wall, 4.0×3.0 cm, along with the tumor, was resected. Reconstruction was performed with an 18mm Cooly double velour graft. Blood pressure was monitored with a pressure probe inserted into the right femoral artery. It did not fall below 60 mmHg during the operation. Local recurrence was observed 10 montns post-operatively, and the patient is now receiving radiation therapy. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 9-10 1992 肺小細胞癌化学療法実施例における重複癌の発生に関する研究 915 922 EN Kenichi Miyake Development of double cancer was evaluated in 337 small cell lung cancer patients who had received intensive chemotherapy with or without radiotherapy. Of them, 14 patients (4.2%) developed a second malignancy: non-small cell lung cancer in six, stomach cancer in four, acute myelogenous leukemia in two, liver cancer in one, and esophagus cancer in one. The relative risk for the development of double cancer calculated by person-year method utilizing age and sex adjusted cancer incidence in Japan was 2.75-fold (P<0.01). The risk of non-small cell lung cancer (8.75-fold) and acute myelogenous leukemia (37.82-fold) was particularly high. The cumulative risk for the development of double cancer was 2.0% at 1 year, 4.1% at 2 years, 14.3% at 3 years, and 100% at 8.1 years. Of 27 patients who survived disease-free for more than 2 years, 10 patients died; five patients (50%) died of double cancer, two died of infectious disease, and only three patients died from recurrent small cell lung cancer. These findings indicate that a cautious follow-up program for the detection of double cancer is indicated in patients with small cell lung cancer. No potential conflict of interest relevant to this article was reported.

岡山大学教育学部 Acta Medica Okayama 0471-4008 139 2008 陶芸制作を通した高齢者への造形活動支援 83 89 EN Hisatoshi Ueta Tetutaro Abe 10.18926/bgeou/14159 高齢化社会である現在、特別養護老人ホーム等高齢者対象福祉施設のニーズが増加している。そこで必要とされる福祉活動は、日常生活の介助、生活空間の提供だけではなく、高齢者がそれぞれ社会を構成する一人として尊重され、施設内外の人と交流し、共に支えあうノーマライゼーションの実践である。そして、心豊かな生活、自身の存在が肯定される活動等、ノーマライゼーションの実践において有用性のある生涯学習「美術」への関心は近年社会的に高まっている。本稿では、このようなノーマライゼーションの実践を目指した陶芸ワークショップの活動内容について報告し、粘土という触覚体験活動で得られるワークショップ参加者の心の変化を検証する。 No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 39 1 2005 Microscopic Surface Change of Polycrystalline Aluminum duringTensile Plastic Deformation 7 15 EN Xiaoqun Wang Takeji Abe Naoya Tada Ichiro Shimizu 10.18926/14135 Roughening on free surface of polycrystalline metal during plastic deformation is closely related to the inhomogeneous deformation in the respective grain at the surface. Uniaxial tensile tests are carried out on annealed pure aluminum sheet specimens with various averaged grain sizes. The roughening is measured by a 3-dimensional stylus instrument to examine the roughness change in both sides of specimen surfaces at each strain. The irregularities on one side are reversed on the backside, when the averaged grain size is as large as the thickness of the specimen. Discussions are made on the relation between the surface shapes of both sides adopting the cross correlation factor. The strains of respective grains are also measured from the grain boundary shape before and after plastic deformation. There are some deviations in the strains of the grains and their standard deviation increases with the applied strain. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 40 1 2006 RNN Based Auto-tuning of PID Control Gains in Hot StripLooper Controller 16 22 EN Yoshihiro Abe Masami Konishi Tatsushi Nishi Jun Imai 10.18926/14098 In this study, auto tuning of PID control gains in hot strip looper controller is made based on RNN model. Neuro emulator is employed to model the characteristics of looper dynamics. Combining neuro emulator and RNN model, auto tuning system of PID control gains is constructed. As the inputs to RNN, plural evaluation functions which reflect individual preference of human experts. Further, Self learning mechamism is embeded to RNN model which enables adaptation to the change in rolling chracteristics. Through numerical experiments, the effect of the proposed method is ascertained. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 105 5-6 1993 甲状腺腫瘍の核DNA量と生物学的悪性度に関する研究 475 487 EN Yuji Onoda To evaluate the biological malingnacy of differentiated thyroid cancer, we determined the nuclear DNA content in thyroid tumors by flow cytometry using paraffin-enbedded materials. The subjects were 80 patients with thyroid tumors. The thyroid tumors were follicular adenoma in 11 cases and thyroid cancer in 69 cases. Of the 69 cases of thyroid cancer, 42 were histologically classfied as papillary carcinoma, 18 as follicular carcinoma, 3 as medullary carcinoma and 6 as anaplastic carcinoma. DNA ploidy pattern and the percentage of proliferating phase cells were analyzed in relation to the prognosis and the following clinicopathological findings : age, gender, histological type, tumor size (t), extrathyroidal invasion (Ex), lymph node metastases (n) and distant metastases (M). DNA ploidy pattern correlated with histological type (p<0.005), but did not correlate with other clinicopathological findings. The percentage of prolipherating phase cells correlated with age (p<0.01) and the histlogical type (p<0.05), but did not correlate with other clinicopathological findings. The percentage of proliferating phase cells correlated with age (p<0.01) and the histological type (p<0.05), but did not correlate with other clinicopathological findings. The comulative survival rate (Kaplan- Meier) of differentiated carcinomas was worse in the aneuploid group than in the diploid group (p<0.0001). the percentage of proliferaging phase cells increased as the prognosis deteriorated. The results suggest that flow cytometric DNA analysis may be useful to evaluate biological malignancy of thyroid tumors. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 106 3-4 1994 喀血を主訴に来院した気管支結石の1例 299 304 EN Yasunori Ishii Fumiyuki Inoue Ryuhan Shin Shinji Ishizuka Naoto Funaki Tomoyoshi Muramatsu Yasuaki Kamikawa Noriaki Tanaka Kunzo Orita Koji Oda Kenji Seo A 62-year-old male was admitted because of hemoptysis. The chest X-ray showed an infiltrative shadow in the right upper lung field. Tomograms and CT scans also showed an infiltrative shadow and small calcifications in the same field. Examination by bronchoscopy revealed bronchial bleeding from the depth of the right B1b. Although the detailed view was unclear due to bleeding, we did not find any growth or any mucosal abnormality. We examined only the bronchial washing cytology. The result was Papanicolaou class Ⅱ. However, we could not rule out malignancy, so we decided to perform a right upper lobectomy. A bron-cholith was seen in the B1b and a hematoma was also seen on its periphery. The stone components were calcium carbonate (74%) and calcium phosphate (26%), suggesting that the stone was caused by mucus retention. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 105 11-12 1993 Myelodysplastic syndrome (MDS) における好中球スーパーオキサイド産生能に関する研究 919 932 EN Noritoshi Inagaki Myelodysplastic syndrome (MDS) are hematological disorders with the potential of progressing to acute leukemia. MDS patients occasionally die of infection despite the absence of severe pancytopenia prior to overt leukemia. Superoxide anion (O(2)(－)) production leads to intracellular bactericidal activity by neutrophils, particularly in an oxygen-dependent system. In this paper, O(2)(－) production by neutrophils in 15 MDS patients [11 patients with refractory anemia with excess of blasts (RAEB) and 4 patients with RAEB in transformation (RAEB-t)] was examined to evaluate possible causes of enhanced susceptibility to infection and to gain information concerning the pathophysiology and prognosis. The following results were obtained : (1) The O(2)(－) production by neutrophils (O(2)(－) production) in 15 MDS patients was lower than that in healthy controls (3.75±2.93 vs 6.20±1.53 nmol/min/10(6) neutrophils, p<0.05). Three of the 15 MDS patients showed little O(2)(－) production. (2) There was inverse correlation between O(2)(－) production and the percentage of leukemic cells in the marrow in acute leukemia (r=0.55, p<0.01), but not in MDS. (3) The O(2)(－) production in 5 MDS patients showing morphological anomalies in a high percentage of neutrophils significantly lower than that in 10 MDS patients showing morphological anomalies in a low percentage of neutrophils (1.04±1.37 vs 5.15±2.50 nmol/min/10(6) neutrophils, p<0.05). (4) The O(2)(－) production in 5 patients with frequent fever (≧38℃) -episodes was significantly lower than that in 10 MDS patients with infrequent fever-episodes (2.22±2.15 vs 4.49±2.83 nmol/min 10(6) neutrophils, p<0.05). (5) Comparison of the O(2)(－) production between MDS patients with and without progression to overt leukemia showed no significant difference (4.25±3.26 vs 3.28±2.76 nmol/min/10(6) neutrophils). These findings suggest that impaired O(2)(－) production by neutrophils, probably due to the faulty differentiation from abnormal hematopoietic clones, is one possible cause of enhanced susceptibility to infection in MDS, and may provide clues for clinical management of infection, but is not useful for early detection of progression to overt leukemia. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 105 11-12 1993 急性白血病寛解導入療法における骨髄内白血病細胞減少動態に関する研究 903 918 EN Makoto Takeuchi An equation was developed to describe the kinetics of leukemic cell destruction in bone marrow during induction chemotherapy for acute nonlymphocytic leukemia (logZ＝K(1)t(4)＋K(2)t(3)＋K(3)t(2)＋K(4), where Z＝leukemic cell number, t＝time, and K＝a constant). The leukemic cell destruction curve was biphasic ; phase Ⅰ was the period from the initiation of a decrease in cells to the maximum velocity of the decrease, and phase Ⅱ was the subsequent period to the cessation of decrease. The following parameters were established : duration and acceleration of decrease in phases Ⅰ and Ⅱ, maximum velocity of decrease, duration of reduction, and residual volume of leukemic cells. 1. Patients who achieved CR showed a longer duration of phases Ⅰ and Ⅱ, a lower acceleration of the decrease in phase Ⅱ, and smaller residual leukemic cell volume than patients who did not achieve CR. there were no significant differences of parameters related to FAB classification, type of induction therapy, or the age of the patients. 2. This equation could be adapted to explain erythroblast kinetics during induction chemotherapy. There were no significant differences of the parameters with respect to the effect of induction therapy and patient age. 3. Patients with high acceleration of the decrease in phase Ⅱ had a short duration of CR and survival. The leukemic cell destruction curve was thought to be useful not only for evaluation of the effect of induction therapy, but also for establishment of post-remission chemotherapy. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 120 3 2008 XV 放射線治療 313 320 EN Mitsuhiro Takemoto Norihisa Katayama Kuniaki Katsui Susumu Kanazawa No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 105 1-2 1993 Colony assay 法を用いた肺癌化学療法における Anthracycline-anthraquinone 系薬剤の有効性に関する研究 第1編 ヒト肺癌細胞株に対する Anthracycline-anthraquinone 系薬剤の殺細胞効果の比較 73 80 EN Takeyuki Numata In an attempt to evaluate the antitumor activity of new anthracycline-anthraquinone analogues ; aclarubicin (ACR), tetrahydropyranyl adriamycin (THP-ADM), and mitoxantrone(MIT), these analogues were compared with adriamycin(ADM) in terms of 70% lethal dose by colony assay using five human lung cancer cell lines, which had been established and maintained in our laboratory. The human lung cancer cell lines tested were EBC-1, an epidermoid cancer cell line, ABC-1, an adenocarcinoma cell line, and SBC-1, -2, and -3, small cell cancer cell lines. In general, the EBC-1 established from a patient tumor showing resistance to ADM was the least sensitive to the drugs tested, and SBC-3 established from a patient tumor with no prior chemotherapy was the most sensitive to the drugs. In antitumor activity, both ACR and THP-ADM appeared to be superior to ADM and MIT, suggesting the clinical usefulness of these drugs in the treatment of lung cancer. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 105 7-8 1993 温熱感受性の異なる培養細胞の DNA 合成に対する温熱効果―フローサイトメトリーによる研究― 771 778 EN Seiryou Tanaka The effect of heat on DNA synthesis in HeLa S3 cells and L-5 cells was studied using flowcytometry. When D(0) values obtained from survival curves of Ehrlich ascites tumor cells, L-5 cells, HeLa S3 cells and NIH3T3 cells after heating to 43, 44, or 45℃, were compared, HeLa S3 cells were resistant and L-5 cells were sensitive to heating. During heating at 43℃, DNA synthesis (BUdR uptake) of HeLa S3 cells was resistant compared to that of L-5 cells. When the period of DNA synthesis was divided into 3 fractions (early S, mid S and late S), late S phase was the most sensitive fraction to heating at 43℃ for 60 minutes. From these results, relationship between DNA synthesis and thermocytotoxic effects are discussed. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 106 11-12 1994 担癌マウスならびに胃癌患者における Cyclophosphamide と Indomethacin による薬物学的摘脾効果の可能性，および外科的摘脾と免疫化学療法併用に関する研究 1125 1142 EN Jiro Yui Using tumor-bearing C(3)H/He mice, in which syngeneic MH-134 tumor cells were transplanted into the back subcutaneously, the possibility of drug-induced splenectomy using cyclophosphamide (CY) and indomethacin (INDO), the timing of chemo- and immuno-therapy, and the usefulness of the combination of surgical splenectomy with immunotherapy were investigated. In patients with gastric cancer, the significance of splenectomy and its combination with immunochemotherapy was also studied. The administration of CY in mice on day 3 after tumor transplantation in the initial stage of the tumor prolonged the survival time, while INDO under the same condition shortened it only when administered on day 3 after transplantation. The administration of an immunopotentiator, OK-432, prior to CY administration shortened the survival time, compared with that of single administration of CY, whereas the OK-432 administration on day 2 after the administration of CY prolonged the survival time. In the immunochemotherapy in which CY was administered on day 7 after transplantation of tumor and OK-432 was given every two days after additional 2 days, the anti-tumor effect of drug-induced splenectomy was not observed as judged from the tumor proliferating curve, but the splenectomy on day 3 after tumor transplantation, in the initial stage of the tumor, prolonged tne survival time. Similar results were observed, when INDO was used instead of CY. The concomitant splenectomy in the initial stage of gastric cancer resulted in a more effective prolongation of survival time. In the cases with adjuvant immunochemotherapy, preservation of the spleen in advanced cancer and splenectomy in the terminal stage of cancer were found to be preferable for effective prolongation of the survival time. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 106 9-10 1994 自律神経機能検査としての顔面浸水負荷テストの有用性の検討―糖尿病患者と健常人における心拍変動性の比較検討― 1003 1012 EN Nana Honma We examined the heart rate response to face immesion in 17 normal subjects and 9 diabetics. The subjects immersed their face fully in a basin filled with ice water at 4-6℃ in a foward leaning position for 20 sec. Two-lead electrocardiogram (ECG) was continuously recorded from 20 sec before the immersion to 5 min after. The R-R intervals were measured on the recorded ECG. In the control group, heart rate response to face immesion showed 4 pahses : an initial increment after the immersion of the face (phase 1), decrease after the initial increment (phase 2), second increment after phase 2 (phase 3) and second decrease after the second increment (phase 4). Repeated face immersion test with a 10 min interval revealed reproducibility of the test. Parasympathetic blockade with atropine sulphate attenuated the pahse 2 response, suggenting that cardiac parasympathetic nerve tone increases in response to the initial increment in the heart rate due to sympathetic response. In diabetic patients, phase 2 response was reduced in patients with a shorter history of diabetes, while in patients with a longer history, heart rate response was diminishied in all phases. Therefore, heart rate response to face immersion was attenuated relative to the duration of the illness. The present study suggests that the analysis of the heart rate response to face immersion in useful as an autonomic nervous function test. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 106 9-10 1994 DIC胆嚢陰性例および上腹部開腹既往症例に対する腹腔鏡下胆嚢摘出術の検討 939 946 EN Hidenori Kondo Teru Okitsu Masami Kondo Hiromu Tsuge Kunzo Orita Between July 1991 and December 1993, 80 patients with gallstone and/or gallbladder polyp were considered candidates for laparoscopic cholecystectomy. We attempted 7 cases of laparoscopic cholecystectomy for patients with nonvisualizing gallbladder by DIC, and in 6 cases, the laparoscopic cholecystectomy was successfully completed. In the remaining 1 case the operation was converted to open cholecystectomy due to severe acute cholecystitis. During the same period, there were 8 patients who had previous upper abdominal surgery, and in 4 of these patients, laparoscopic cholecystectomy was successfully completed. All patients were free of major complications intra and postoperatively. We can extend the indications for laparoscopic cholecystectomy as skill with this procedure increases. We believe that this procedure will become the standard operation for benign gallbladder diseases in the near future in Japan. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 106 7-8 1994 腹腔鏡下胆嚢摘出術75例の経験 771 778 EN Hidenori Kondo Teru Okitsu Masami Kondo Hiromu Tsuge Kunzo Orita We peformed 75 consecutive laparoscopic cholecystectomy from July 1991 to October 1993 on the patients with gallstones and/or gallbladder polyps. The patients consisted of 30 males and 45 females between 32 and 88 years old with a mean age of 59.4 years. In 72 of these 75 patients (96.0%) laparoscopic cholecystectomy was successfully completed. In the remaining 3 cases (4.0%) the operation was converted to the open cholecystectomy. All patients were free of major complications. Three patients required conversion to a conventional open cholecystectomy due to fallen gallstones in the peritoneal cavity, dense adhesions surrounding the gallbladder and severe acute cholecystitis. This procedure is advantageous in comparison with the conventional open cholecystectomy, because of less postoperative pain, rapid postoperative recovery and high cosmetic value as well. Laparoscopic cholecystectomy seems to be a safe and effective treatment for selected patients with benign gallbladder diseases. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 110 11-12 1999 Teratomatosis Peritonei―卵巣奇形腫由来の腹膜播種性病巣に関する文献学的考察：今世紀報告された156例の臨床病理学的検討による集大成― 171 210 EN Masanao Kobayashi Jun-ichi Kobayashi Hiromi Iwagaki Noriaki Tanaka We performed clinicopathological analyses of peritoneal dissemination caused by ovarian teratoma (PD caused by OV-T), on the English great table of 156 cases in 105 papers published in this century. We classified PD caused by OV-T into 3 categories as follows ; 1. (TP) teratomatosis peritonei (new term) : PD composed by three germ teratomas cells. 2. (GP) gliomatosis peritonei : PD composed by only glia cells. 3. (MIX) mixed type : PD composed by glia and teratoma cells. TP and MIX were newly designated in this present paper. The number of TP, GP and MIX were 22, 95 and 25, respectively. The review of these 156 cases and 105 papers were demonstrated that the clinical features between GP and TP were cleary different. TP had a more tendency of recurrentn character in comparison to GP and MIX, but had a good long survivals resulted by repeated surgical resections. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 110 7-10 1998 胃癌を伴った胃グロームス腫瘍の1例―本邦報告例の文献的考察― 107 114 EN Kazuma Fukuda Hiroaki Asano Yuu Otani Naoyuki Miyaguti Hideyuki Nishi Masayuki Mano Shoukiti Komatubara Takumi Kishimoto The patient was a 67-year-old man who vomitted blood during therapy while hospitalized due to an asthma attack. He underwent a gastric examination, which detected a submucosal tumor on the greater curvature of the gastric antrum and gastric cancer on the lesser curvature. This tumor was diagnosed as a glomus tumor by postoperative pathological examination. In Japan, glomus tumors of stomach have been reported in 50 cases including our case. The mean age of patients was 48 years (23 to 74). Nineteen patients were male and 31 female. The main symptom was upper abdominal pain. The tumors developed in the submucosal layer of the greater curvature in the antrum and the mean size was 2.8 cm. A Angiography revealed hypervascularization and endoscopic ulutasonography showed spheroid tumors localized in the muscle layer. Proeoperative histological diagnoses were often difficult. Two cases including our patient were associated with gastric cancer. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 109 3-6 1997 紫外線の脈絡膜循環に及ぼす影響 41 49 EN Nobuhiko Idei The effects of near-ultraviolet radiation on choroidal blood flow were studied in aphakic rabbit eyes. After lens extraction, eyes were exposed to monochrometic nera-ultraviolet radiation with a wavelength of 365 nm and radiant exposure of 8.0 J/cm2. Choroidal blood flow was measured by the hydrogen clearance method 3, 7 and 14 days after exposure. Eyes were enucleated after the measurement of choroidal blood flow and examined histopathologically. Choroidal blood flow in the eyes wan significantly reduced 7 and 14 days after exposure compared with control eyes. Histopathologically, the photoreceptors showed markde destruction 3, 7 and 14 days after exposure, while the retinal pigment epithelium and choriocapillaris remained intact during this period. These results suggested that choroidal blood flow was reduced by decreased oxygen consumption in the outer retina as a result of the destruction of photoreceptors after exposure to near-ultraviolet radiation. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 112 3-8 2000 要介護高齢者における口臭とその関連要因及び予防対策に関する研究 47 64 EN Masahiko Egusa One hundred ten elderly with disabilities in institutions or receiving home care were selected and informed. This study focused on oral malodor and discusses consent was obtained the relationship between oral malodor and the state of dental health and oral hygiene in the elderly with disabilities. ADL of the elderly with disabilities (rank J, A, B, C, settled by National Health Administration in Japan) were 8.2% at rank J, 28.2% at rank A, 42.7% at rank B and 20.9% at rank C, respectively. The incident rate of swallowing pneumonitis, fever and bedsores were low. Accordingly, physical and mental conditions were comparatively preferable. Tooth and periodontal conditions were comparablye to nationwide results. 1. The elderly in poor ADL had marked oral malodor compared with those in good health. 2. The elderly who required assistance to eat or had special dietary requirements had marked oral malodor. 3. The elderly who had normal oral functions and the ability to take care of their own oral hygiene had markedly less oral malodor. 4. The elderly who had poor oral hygiene exhibitings thick tongue coating and positive results in a Candida albicans culture test, had marked oral malodor. 5. Using, the multivariate statistical analysis of Hayashi methodsⅡ, the coefficient of correlation between the state of oral malodor and 27 variables was obtained. 1) The study obtained trustworthy values that discriminate analysis 92.7% and correlation ratio is 0.53. 2) The variables related to severe oral malodor, extracted by the multivariate statistical analysis in descending order, were: "low level of ADL in gargling and denture brushing", "cigarette smoking", "speech disabilities", "unsatisfactory mastication", "need for special dietary care", "oral druyness", "gingivitis", "soft diet of side dish", "living in a special institution caring for the elderly", "thick tongue coating", and "a positive Candida albicans culture test", respectively. 3) The items related with comparatively comfortable or bearable oral malodor, extracted by the multivariate statistical analysis in descending order were : "satisfactory mastication", "home care", "healthy or poor eyesight", "difficulty in mastication", "being able to independently remove, dentures", "a negative Candida albicans culture test", "no oral dryness", "independents in selecting diet", "comfortable gingival condition", "being dependent on others for tooth-brushing" and "preferable tongue coating", respectively. 4) For the effective preventive countermeasures of oral malodor, ADL of oral health, caring circumstances and hygiene of gingiva/tongue should be focused on rather than dental hygiene itself. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 112 9-12 2000 男性喫煙者の禁煙実行要因に関する研究 183 189 EN Yuichi Kawada This syudy was designed to clarify what factors influenced the ability to stop smoking in male smokers, from the viewpoint of life-style guidance and primary care. Of the people who attended abult health examinations between 1993 and 1998 in Okayama Ctiy, 987 male smokers were selected and categorized according to the number of cigarettes per day into three groups. The relation was analyzed statistically between the three groups and the life-style related factors : age, the degree of obesity, sleep, snacks, salt, exercise and alcohol. The results showed significant differences in age, the degree of obesity, sleep, salt, exercise. Second, the relation between threse three groups and the experience and duration of smoking cessation was analyzed. The results showed a significant differnce in the experience of smoking cessation, but no significant differnce in duration of smoking cessation. The conclusions are as follows : 1. Male smokers, who do not activedy try to improve of their life-style related factors, have fewer experiences of smoking cessation, 2. Male smokers who try to improve their life-style habits have a similar period od smoking cessation to those who do not. 3. Long term support for all male smokers to continue to be non-smoking is important. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 113 3 2001 プリオン病 299 300 EN No potential conflict of interest relevant to this article was reported.

岡山大学環境理工学部 Acta Medica Okayama 1341-9099 8 1 2003 The Impact of Core-cities Growth on the Regional Economic Development in China 27 38 EN Dagang Zou Hirofumi Abe 10.18926/fest/11498 China has achieved a remarkable economic growth in the past two decades. However, the rapid economic development has led to regional disparities between the advanced coastal regions and the other regions. Regional development planning in China has sought to achieve the redress of regional disparities as well as a high economic growth. This paper aims to examine the role of core cities in the development of Chinese regional economy and their impact on regional differentials. Following a brief review of regional development planning in China, the paper examines the role of core cities on the regional development and the trends in regional disparities using data for seven coastal provinces (Guangdong, Fujian, Zhejiang, Jiangsu, Shandong, Hebei and Liaoning) and three municipalities (Beijing, Tianjin and Shanghai) in the period 1989-1997. It shows that while the coastal regions achieved a high economic growth, the extent of regional disparities and the contributions of core cities to the reduction of economic differentials varied among provinces. The paper concludes by proposing future issues on regional development planning in China. No potential conflict of interest relevant to this article was reported.

社団法人日本機械学会 Acta Medica Okayama 0387-5016 64 618 1998 傾斜配置した平板状形状安定化潜熱蓄熱材充填矩形蓄熱槽の蓄熱特性 200 207 EN Hideo Inaba Tu Ping Akihiko Horibe Koichi Ozaki The present study deals with the heat storage characteristics of the inclined rectangular vessel packed with spape-stabilized paraffin plates as a latent heat storage material by numerical analysis. It was found that the heat storage characteristics were remarkedly affected by the inclination angle of the rectangular vessel and the heat transfer medium flow direction, due to the presence of natural convection in the fluid flow channel between the paraffin plates. Numerical results revealed flow patterns, temperature profiles and heat storage characteristics for various inclination angles, inlet velocities and temperatures of the heat transfer medium fluid, and widths of the fluid flow channel. No potential conflict of interest relevant to this article was reported.

岡山大学農学部 Acta Medica Okayama 0474-0254 93 1 2004 コレステロール負荷によって発症したニワトリ胸部大動脈と冠状動脈における動脈硬化症 45 49 EN Yasuhiro Kondo Sachika Honjo Kazumasa Ohtsuki Asaki Abe Hypercholesterolemia and hyperlipidemia have been important in human health as factors that induce atherosclerotic lesions in brain and heart blood vessel. Various experimental studies have been done to prevent and treat atherosclerotic lesions in animals. In the present study, we assessed the suitability of chickens as experimental animal for atherosclerosis. Newly hatched chicks were fed on 1.0%-or 0.1%-cholesterol(CHO) containing feed. After 3 and 6 months, total cholesterol levels in the sera and histological changes in the aorta and coronary artery of chicks fed on 1.0%-CHO-containing feed for 3 and 6 months, intimal thickening and marked accumulation of foam cells were observed. Endothelial cells had disappeared in the aorta of these chicks. A slight accumulation of foam cells was observed in the aortic intima of chicks fed on 0.1%-CHO-containing feed. In the coronary artery, a remarkable thickening of intima with accumulation of foam cells and a marked stenosis of coronary space were observed in chicks fed on 1.0%-CHO-containing feed. The results of present study indicate that the chicken can be a useful experimental animal in the study of hypercholesterolemia, hyperlipidemia and atherosclerosis. No potential conflict of interest relevant to this article was reported.

岡山大学農学部 Acta Medica Okayama 0474-0254　 96 1 2007 Role of the Surface IgM-Inducing Factor in Development of B Lymphocytes in Chicken Embryonic Bursa of Fabricius 55 58 EN Song Han Asaki Abe Kiyoaki Narahara Yasuhiro Kondo 　The bursa of Fabricius plays essential roles in the establishment of immune functions of avian species as a primary site for differentiation and proliferation of B lymphocytes. The bursa of chick embryos is colonized by lymphoid cell precursors only between the days 7th of embryogenesis (E7) and E14. Susceptibility to the sIgM-inducing factor may fluctuate in bursal lymphoid cells during the lymphoid precursor cell-receptive period. In the present study, the dynamic changes in the sIgM-positive ratio and responsiveness to sIgM-inducing factor were examined in lymphoid cells sampled from the bursa during the B precursor cell-receptive period (E10 to E13) and findings suggest that responsiveness to sIgM-inducing factor varies with the development of the chick embryos. E11 is suggested to be a critical stage of B-lymphocytegenesis in the bursa of chick embryos. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2001 超イオン導電体における異常電気伝導度に関する研究 -緩和モード理論による解析- EN No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1997 持続的圧力による義歯床下組織の病理組織学的変化に対する糖尿病の影響に関する実験的研究 EN No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1968 人工栄養自律哺乳に適した粉乳汁の蛋白組成に関する研究 EN Takeshi Abe No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1966 脾の比較組織学的研究 EN No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1993 Production of experimental staphylococcal impetigo in mice EN Yoshiko Abe No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1974 Effect of immunization with fetal cells on adenovirus-12 oncogenesis EN No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1994 The complete primary structure of the long form of mouse α 1 (Ⅸ) collagen chain and its expression during limb development EN Nobuhiro Abe No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1972 ネコの視床後腹側核の視床内結合に関する実験解剖学的研究 EN Kumashige Abe No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1999 High-performance liquid chromatographic determination of β-alanine,β-aminoisobutyric acid and γ-aminobutyric acid in tissue extracts and urine of normal and (aminooxy) acetate-treated rats EN No potential conflict of interest relevant to this article was reported.