Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Time Course of the Development and Loss of Delta-9-tetrahydrocannabinol Tolerance: Effects on Hypothermia and Spontaneous Locomotor Activity in Mice 47 54 EN Yukiomi Eguchi Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Soichiro Ushio Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Keiichi Irie Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Yuta Yamashita Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Miyu Eguchi Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Takafumi Nakano Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Kenichi Mishima Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Original Article 10.18926/AMO/70072 Deregulation of cannabis use is gradually expanding in Europe and the United States. However, the biological processes driving tolerance to delta-9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component of cannabis, remain unclear. Thus, this study aimed to investigate the mechanisms and time course of tolerance development and loss to Δ9-THC in mice. Male ICR mice (7 weeks old) were administered Δ9-THC once daily for 3 days and then divided into three groups according to the washout period (3-, 10-, and 17-day washout groups). After each washout, changes in body temperature and locomotor activity were measured following re-exposure to Δ9-THC. Furthermore, the mRNA expression levels of CB1 and CB2 receptors in the brain were evaluated using real-time PCR. On day 1, significant hypothermia and reduced spontaneous locomotor activity were observed in the Δ9-THC-treated mice compared with the vehicle-treated mice. Tolerance to the hypothermic and locomotor-suppressing effects of Δ9-THC developed on days 2 and 3, respectively, and dissipated after 3 and 11 days of washout, respectively. These differences in the rates of tolerance development and recovery may reflect distinct underlying mechanisms. No significant changes in receptor mRNA expression were observed. These findings highlight the complexity of Δ9-THC tolerance and its potential implications for long-term cannabis use. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Effects of Thoron Inhalation and Cyclosporin A Treatment on Dextran Sulfate Sodium-Induced Oxidative Damage in Mice 421 429 EN Ayumi Tanaka Graduate School of Health Sciences, Okayama University Shota Naoe Graduate School of Health Sciences, Okayama University Reiju Takenaka Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/69844 Radon (222Rn; Rn) and thoron (220Rn; Tn) inhalation have been reported to enhance antioxidant activity in various organs. However, the effects of Tn on the colon have not been investigated. This study aimed to clarify the effects of Tn inhalation, alone and in combination with cyclosporin A (CsA), on dextran sulfate sodium (DSS)-induced colitis, and the accompanying oxidative stress, in mice. Male BALB/c mice were subjected to continuous 8-day Tn inhalation (c-Tn, 533±128 Bq/m3) or alternate-day Tn inhalation over the same period (f-Tn, 577±63Bq/m3), followed by treatment with 3% DSS and either CsA or vehicle for 7 days. Although the disease activity index (DAI) decreased significantly by day 2 in the c-Tn group, scores remained significantly higher than those in the f-Tn group. In the c-Tn group, superoxide dismutase and catalase activity in the colon were significantly elevated compared with those in sham controls. Thus, DSS-induced damage was effectively inhibited in the earlier stages by the c-Tn mode of inhalation than by the f-Tn mode. These findings suggest that continuous Tn inhalation more effectively attenuated early colitis symptoms than alternate-day inhalation, potentially through upregulation of antioxidant defenses. Tn and CsA showed no combined effects. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0021-9606 163 22 2025 Fourier-transform infrared spectroscopy of hydrogen fluoride dimers in solid parahydrogen 224312 EN Yuki Miyamoto Research Institute for Interdisciplinary Science, Okayama University Hiroki Ooe Graduate School of Natural Science and Technology, Okayama University Susumu Kuma Department of Physics, Rikkyo University We investigate the Fourier-transform infrared spectra of hydrogen fluoride dimers in solid parahydrogen, the detailed analysis of which has remained unexplored. We propose a plausible analysis based on concentration dependence, light polarization, annealing, and time evolution. The absorption lines exhibited multiple peaks, with intensity ratios significantly altered by annealing and by time evolution at a constant temperature. The spectral patterns and isotopic effects suggest that the dimers do not rotate freely in solid parahydrogen, while multiple peaks arise from different stable structures, including single and double substitution sites. Unlike in the gas phase and helium droplets, no tunneling splitting was observed. The broad ν1 band suggests that some dimer structures may exhibit axial rotation. Spectral changes due to annealing likely result from site conversion, while observed IR-induced changes indicate preferential dissociation of dimers in double substitution sites. These findings still remain tentative, necessitating further experimental and theoretical studies. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1433-7851 64 13 2025 Conduction Band and Defect Engineering for the Prominent Visible‐Light Responsive Photocatalysts e202419624 EN Akira Yamakata Graduate School of Natural Science and Technology, Okayama University Kosaku Kato Graduate School of Natural Science and Technology, Okayama University Takafumi Ogawa Nanostructures Research Laboratory, Japan Fine Ceramics Center Kanta Ogawa Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Makoto Ogawa Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Daichi Kato Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Chengchao Zhong Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Akihide Kuwabara Nanostructures Research Laboratory, Japan Fine Ceramics Center Ryu Abe Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Hiroshi Kageyama Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Controlling trap depth is crucial to improve photocatalytic activity, but designing such crystal structures has been challenging. In this study, we discovered that in 2D materials like BiOCl and Bi4NbO8Cl, composed of interleaved [Bi2O2]2+ and Cl- slabs, the trap depth can be controlled by manipulating the slab stacking structure. In BiOCl, oxygen vacancies (VO) create deep electron traps, while chlorine vacancies (VCl) produce shallow traps. The depth is determined by the coordination around anion vacancies: VO forms strong σ bonds with Bi-6p dangling bonds below the conduction band minimum (CBM), while those around Cl are parallel, forming weak π-bonding. The strong re-hybridization makes the trap depth deeper. In Bi4NbO8Cl, VCl also creates shallow traps, but VO does not produce deep traps although Bi-6p orbitals are also forming strong σ bonding. This difference is attributed to the difference of the energy level of CBM. In both cases, the CBM consists of Bi-6p orbitals extending into the Cl layers. However, these orbitals are isolated in BiOCl, but those in Bi4NbO8Cl are bonded with each other between neighboring [Bi2O2]2+ layers. This unique bonding-based CBM prevents the formation of deep electron traps, and significantly enhances H2 evolution activity by prolonging the lifetime of highly reactive free electrons. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0021-9606 163 19 2025 Interplay of coil–globule transitions and aggregation in homopolymer aqueous solutions: Simulation and topological insights 191101 EN Junichi Komatsu Department of Chemistry, Faculty of Science, Okayama University Kenichiro Koga Department of Chemistry, Faculty of Science, Okayama University Jonas Berx Niels Bohr International Academy, Niels Bohr Institute, University of Copenhagen We investigate the structural and topological properties of hydrophobic homopolymer chains in aqueous solutions using molecular dynamics simulations and circuit topology (CT) analysis. By combining geometric observables, such as the radius of gyration and the degree of aggregation, with CT data, we capture the relationship between coil–globule and aggregation transitions, resolving the system’s structural changes with temperature. Our results reveal a temperature-driven collective transition from isolated coiled chains to globular aggregates. At a characteristic transition temperature Tc, each chain in multichain systems undergoes a rapid coil–globule collapse, coinciding with aggregation, in contrast to the gradual collapse observed in single-chain systems at infinite dilution. This collective transition is reflected in geometric descriptors and a reorganization of CT motifs, shifting from intrachain-dominated motifs at low temperatures to a diverse ensemble of multichain motifs at higher temperatures. CT motif enumeration provides contact statistics while offering a topologically detailed view of polymer organization. These findings highlight CT’s utility as a structural descriptor for polymer systems and suggest applications for biopolymer aggregation and folding. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2399-3669 8 1 2025 Synthesis of thienoacenes by electrochemical double C–S cyclization using a halogen mediator 366 EN Koichi Mitsudo Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takuya Nagahara Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nozomi Kataura Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuka Okamura Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Toki Yonezawa Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuri Tachibana Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nolan Soulié Faculty of Science and Engineering, Sorbonne Université Keisuke Shigemori Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Eisuke Sato Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroki Mandai Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science Seiji Suga Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Thienoacenes are significant compounds as organic materials. One of the most efficient ways to synthesize thienoacenes is to form multiple C–S bonds in a single step. Because unprotected S–H bonds are easily oxidized to S–S bonds, S-Me protected substrates are commonly used for the purpose. However, their reactivity is insufficient, and one-step construction of multiple C–S bonds is still challenging. We herein report the electrochemical synthesis of thienoacenes from S-methoxymethyl (MOM)-protected diarylacetylenes. In the presence of Bu4NBr as a halogen mediator, electrochemical double C–S cyclization of diarylacetylenes bearing two MOM groups proceeded to afford [1]benzothieno[3,2-b][1]benzothiophene (BTBT) derivatives. While S-Me or S-p-methoxybenzyl (PMB)-protected diarylacetylenes did not afford BTBT, BTBT was selectively obtained when a substrate protected with S-MOM groups was used. The S-MOM protection strategy is also effective for the electrochemical synthesis of a more π-expanded thienoacene such as dibenzo[d,d′]thieno[3,2-b,4,5-b′]dithiophene (DBTDT). No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2694-2437 4 5 2024 New Catalytic Residues and Catalytic Mechanism of the RNase T1 Family 257 267 EN Katsuki Takebe Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mamoru Suzuki Institute for Protein Research, Osaka University Yumiko Hara Institute for Protein Research, Osaka University Takuya Katsutani Institute for Protein Research, Osaka University Naomi Motoyoshi School of Pharmacy, Nihon University Tadashi Itagaki School of Pharmacy, Nihon University Shuhei Miyakawa Graduate School of Pharmaceutical Sciences, Osaka University Kuniaki Okamoto Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaori Fukuzawa Graduate School of Pharmaceutical Sciences, Osaka University Hiroko Kobayashi School of Pharmacy, Nihon University The ribonuclease T1 family, including RNase Po1 secreted by Pleurotus ostreatus, exhibits antitumor activity. Here, we resolved the Po1/guanosine-3′-monophosphate complex (3′GMP) structure at 1.75 Å. Structure comparison and fragment molecular orbital (FMO) calculation between the apo form and the Po1/3′GMP complex identified Phe38, Phe40, and Glu42 as the key binding residues. Two types of the RNase/3′GMP complex in RNasePo1 and RNase T1 were homologous to Po1, and FMO calculations elucidated that the biprotonated histidine on the β3 sheet (His36) on the β3 sheet and deprotonated Glu54 on the β4 sheet were advantageous to RNase activity. Moreover, tyrosine (Tyr34) on the β3 sheet was elucidated as a crucial catalytic residues. Mutation of Tyr34 with phenylalanine decreased RNase activity and diminished antitumor efficacy compared to that in the wild type. This suggests the importance of RNase activity in antitumor mechanisms. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2399-3669 7 1 2024 Post-spinel-type AB2O4 high-pressure phases in geochemistry and materials science 189 EN Masaki Akaogi Department of Chemistry, Gakushuin University Takayuki Ishii Institute for Planetary Materials, Okayama University Kazunari Yamaura Research Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science Post-spinel-type AB2O4 compounds are stable at higher pressures than spinel phases. These compounds have garnered much interest in geo- and materials science for their geochemical importance as well as potential application as high ionic conductors and materials with strongly correlated electrons. Here, large-volume high-pressure syntheses, structural features and properties of post-spinels are reviewed. Prospects are discussed for future searches for post-spinel-type phases by applying advanced large-volume high-pressure technology. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0947-8396 131 9 2025 Optical and chemical properties of silver tree-like structure treated with gold galvanic substitution 744 EN Kazushi Honda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuyuki Takeyasu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Galvanic gold substitution was executed in the presence of trisodium citrate on silver tree-like structures. No discernible difference in geometry was observed between the pre- and post-gold substitution phases, which benefited from the presence of citrate ions. The extent of gold substitution was regulated by the amount of gold ion solution added. After the gold substitution, an increase in extinction was observed in the ultraviolet region, indicating that gold was deposited at the surface. Raman scattering of para-toluenethiol was measured on the gold/silver tree-like structures at 488 nm excitations, where a decrease in the Raman peak intensity was observed as the quantity of gold ion solution increased. The results indicated that the optical property of silver was lost due to the increase of the amount of gold deposition. Concurrently, an investigation was conducted into the chemical resistance of the gold/silver tree-like structures, which was evaluated by measuring the resistivity inverse-proportional to the amount of silver ions dissolved by the diluted nitric acid. As the amount of gold ion solution added increased, the resistivity increased and became constant. The result implied that the surface chemical property had undergone a complete transformation into gold. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0009-4536 2025 Elucidation of the relationship between solid‐state photoluminescence and crystal structures in 2,6‐substituted naphthalene derivatives EN Minoru Yamaji Department of Applied Chemistry, Division of Materials and Environment, Graduate School of Science and Engineering, Gunma University Isao Yoshikawa Department of Materials and Environmental Science, Institute of Industrial Science, The University of Tokyo Toshiki Mutai Technology Transfer Service Corporation Hirohiko Houjou Department of Materials and Environmental Science, Institute of Industrial Science, The University of Tokyo Kenta Goto Institute for Materials Chemistry and Engineering, Kyushu University Fumito Tani Institute for Materials Chemistry and Engineering, Kyushu University Kengo Suzuki Hamamatsu Photonics K.K Hideki Okamoto Department of Chemistry, Faculty of Environment, Life, Natural Sciences and Technology, Okayama University Polycyclic aromatic hydrocarbons (PAHs) are known to exhibit fluorescence in solution, but generally do not emit in the solid state, with the notable exception of anthracene. We previously reported that PAHs containing multiple chromophores show solid-state emission, and we have investigated the relationship between their crystal structures and photoluminescence properties. In particular, PAHs with herringbone-type crystal packing, such as 2,6-diphenylnaphthalene (DPhNp), which has a slender and elongated molecular structure, exhibits red-shifted solid-state fluorescence spectra relative to their solution-phase counterparts. In this study, we synthesized 2,6-naphthalene derivatives bearing phenyl and/or pyridyl substituents (PhPyNp and DPyNp) and observed distinct, red-shifted emission in the solid state compared with that in solution. Crystallographic analysis revealed that both PhPyNp and DPyNp adopt herringbone packing motifs. These findings support our hypothesis that the spectral characteristics of PAH emission are closely linked to crystal packing arrangements, providing a useful strategy for screening PAH candidates for applications in organic semiconducting materials. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1433-7851 2025 Development of a Vinylated Cyclic Allene: A Fleeting Strained Diene for the Diels–Alder Reaction e202510319 EN Haruki Mizoguchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takumi Obata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taiki Hirai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Manaka Komatsu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akira Sakakura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Fleeting molecules possessing strained multiple bonds are important components in organic synthesis due to their ability to undergo various chemical reactions driven by the release of strain energy. Although the use of strained π-bonds as 2π components, represented by dienophiles in Diels–Alder reactions, has been well studied, “the strained diene (4π component) approach” for molecular construction remains underexplored. Herein, we report the design of a vinyl cyclic allene (1-vinyl-1,2-cyclohexadiene) as a highly reactive strained diene and the development of its Diels–Alder reactions. Experimental and computational studies of vinyl cyclic allenes revealed that this diene system undergoes cycloaddition with dienophiles regio- and stereoselectively under mild reaction conditions. These studies also provide insight into the reactivity and selectivity of the system. The strained diene approach enables the convergent construction of polycyclic molecules through bond disconnections distinct from conventional retrosynthetic analysis, thus offering an efficient strategy for the assembly of functional molecules. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 Continuous Stimulation with Glycolaldehyde-derived Advanced Glycation End Product Reduces Aggrecan and COL2A1 Production via RAGE in Human OUMS-27 Chondrosarcoma Cells 157 166 EN Omer Faruk Hatipoglu Department of Pharmacology, Faculty of Medicine, Kindai University Takashi Nishinaka Department of Pharmacology, Faculty of Medicine, Kindai University Kursat Oguz Yaykasli Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen Shuji Mori Department of Pharmacology, School of Pharmacy, Shujitsu University Masahiro Watanabe Department of Pharmacology, School of Pharmacy, Shujitsu University Takao Toyomura Department of Pharmacology, School of Pharmacy, Shujitsu University Masahiro Nishibori Department of Translational Research & Dug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Hideo Takahashi Department of Pharmacology, Faculty of Medicine, Kindai University Hidenori Wake Department of Pharmacology, Faculty of Medicine, Kindai University Original Article 10.18926/AMO/68723 Chondrocytes are responsible for the production of extracellular matrix (ECM) components such as collagen type II alpha-1 (COL2A1) and aggrecan, which are loosely distributed in articular cartilage. Chondrocyte dysfunction has been implicated in the pathogenesis of rheumatic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). With age, advanced glycation end products (AGEs) accumulate in all tissues and body fluids, including cartilage and synovial fluid, causing and accelerating pathological changes associated with chronic diseases such as OA. Glycolaldehyde-derived AGE (AGE3), which is toxic to a variety of cell types, have a stronger effect on cartilage compared with other AGEs. To understand the long-term effects of AGE3 on cartilage, we stimulated a human chondrosarcoma cell line (OUMS-27), which exhibits a chondrocytic phenotype, with 10 μg/ml AGE3 for 4 weeks. As a result, the expressions of COL2A1 and aggrecan were significantly downregulated in the OUMS-27 cells without inducing cell death, but the expressions of proteases that play an important role in cartilage destruction were not affected. Inhibition of the receptor for advanced glycation end products (RAGE) suppressed the AGE3-induced reduction in cartilage component production, suggesting the involvement of RAGE in the action of AGE3. No potential conflict of interest relevant to this article was reported.

Beilstein-Institut Acta Medica Okayama 1860-5397 21 2025 Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra 670 679 EN Yuuki Ishii Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Minoru Yamaji Division of Molecular Science, Graduate School of Science and Engineering, Gunma University Fumito Tani Institute for Materials Chemistry and Engineering, Kyushu University Kenta Goto Institute for Materials Chemistry and Engineering, Kyushu University Yoshihiro Kubozono Research Institute for Interdisciplinary Science, Okayama University Hideki Okamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University [n]Phenacenes ([n] = 5-7), octafluorinated at the terminal benzene rings (F8-phenacenes: F8PIC, F8FUL, and F87PHEN), were photochemically synthesized, and their electronic spectra were investigated to reveal the effects of the fluorination on the electronic features of phenacene molecules. F8-Phenacenes were conveniently synthesized by the Mallory photoreaction of the corresponding fluorinated diarylethenes as the key step. Upon fluorination on the phenacene cores, the absorption and fluorescence bands of the F8-phenacenes in CHCl3 systematically red-shifted by ca. 3-5 nm compared to those of the corresponding parent phenacenes. The vibrational progressions of the absorption and fluorescence bands were little affected by the fluorination in the solution phase. In the solid state, the absorption band of F8-phenacenes appeared in the similar wavelength region for the corresponding parent phenacenes whereas their fluorescence bands markedly red-shifted and broadened. These observations suggest that the intermolecular interactions of excited-state F8-phenacene molecules are significantly different from those of the corresponding parent molecules, most likely due to different crystalline packing motifs. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1612-1872 2025 Antifouling Activity of Xylemin, Its Structural Analogs, and Related Polyamines e202403213 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takefumi Yorisue Institute of Natural and Environmental Sciences, University of Hyogo Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Biofouling, which is the accumulation of organisms on undersea structures, poses significant global, social, and economic issues. Although organotin compounds were effective antifoulants since the 1960s, they were banned in 2008 due to their toxicity to marine life. Although tin-free alternatives have been developed, they also raise environmental concerns. This underscores the need for effective, nontoxic antifouling agents. We previously synthesized N-(4-aminobutyl)propylamine (xylemin) and its structural analogs. In this study, we assayed the antifouling activity and toxicity of xylemin, its structural analogs, and related polyamines toward cypris larvae of the barnacle Amphibalanus amphitrite. Xylemin and its Boc-protected analog exhibited antifouling activities with 50% effective concentrations (EC50) of 4.25 and 6.11 µg/mL, respectively. Four xylemin analogs did not show a settlement-inhibitory effect at a concentration of 50 µg/mL. Putrescine, spermidine, spermine, and thermospermine, which are xylemin-related polyamines, did not display antifoulant effects (EC50 > 50 µg/mL). All evaluated compounds were nontoxic at a concentration of 50 µg/mL. These findings indicate that the size and structure of the N-alkyl group are essential for the antifouling activity of xylemin. Therefore, xylemin and its analogs hold promise as nontoxic, eco-friendly antifouling agents, offering a sustainable solution to biofouling in marine environments. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1433-7851 64 8 2025 B,N‐Embedded Helical Nanographenes Showing an Ion‐Triggered Chiroptical Switching Function e202418546 EN Chihiro Maeda Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Sayaka Michishita Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Issa Yasutomo Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tadashi Ema Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Intramolecular oxidative aromatic coupling of 3,6-bis(m-terphenyl-2’-yl)carbazole provided a bis(m-terphenyl)-fused carbazole, while that of 3,6-bis(m-terphenyl-2’-yl)-1,8-diphenylcarbazole afforded a bis(quaterphenyl)-fused carbazole. Borylation of the latter furnished a B,N-embedded helical nanographene binding a fluoride anion via a structural change from the three-coordinate boron to the four-coordinate boron. The anionic charge derived from the fluoride anion is stabilized over the expanded π-framework, which leads to the high binding constant (Ka) of 1×105 M−1. The four-coordinate boron species was converted back to the parent three-coordinate boron species with Ag+, and the chiroptical switch between the three-coordinate boron and four-coordinate boron species has been achieved via the ion recognition with the change in the color and glum values. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 1 2025 Photoinitiators Induce Histamine Production in Human Mast Cells 51 58 EN Taro Miura Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Kawasaki Laboratory of Clinical Pharmacology and Therapeutics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University Hirofumi Hamano Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshito Zamami Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Sendo Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/68362 Photoinitiators are used in the manufacture of many daily products, and may produce harmful effects due to their cytotoxicity. They have also been detected in human serum. Here, we investigated the histamine-producing effects in HMC-1 cells and the inflammatory cytokine release effects in RAW264 cells for four photoinitiators: 1-hydroxycyclohexyl phenyl ketone; 2-isopropylthioxanthone; methyl 2-benzoylbenzoate; and 2-methyl-4´-(methylthio)-2-morpholinopropiophenone. All four promoted histamine production in HMC-1 cells; however, they did not significantly affect the release of inflammatory cytokines in RAW264 cells. These findings suggest that these four photoinitiators induce inflammatory cytokine-independent histamine production, potentially contributing to histamine-mediated chronic inflammation in vitro. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0947-6539 31 14 2025 Graphene Oxide as a Self‐Carbocatalyst to Facilitate the Ring‐Opening Polymerization of Glycidol for Efficient Polyglycerol Grafting e202404400 EN Yajuan Zou Research Institute for Interdisciplinary Science, Okayama University Kentaro Ohkura Graduate School of Natural Science and Technology, Okayama University Israel Ortiz‐Anaya Research Institute for Interdisciplinary Science, Okayama University Ryota Kimura Graduate School of Natural Science and Technology, Okayama University Alberto Bianco Research Institute for Interdisciplinary Science, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Grafting carbon-based nanomaterials (CNMs) with polyglycerol (PG) improves their application potentials in biomedicine and electronics. Although “grafting from” method offers advantages over “grafting to” one in terms of operability and versatility, little is known about the reaction process of glycidol with the surface groups onto CNMs. By using graphene oxide (GO) as a multi-functional model material, we examined the reactivity of the surface groups on GO toward glycidol molecules via a set of model reactions. We reveal that carboxyl groups spontaneously react with the epoxide ring with no need of catalyst, while GO catalyzes the reactions of hydroxyl groups with the epoxide of glycidol. In addition, the hydroxyl group of glycidol can open the epoxide in the basal plane of GO. The subsequent polymerization of PG is supposed to propagate at the primary and/or the secondary hydroxyl groups, generating a ramified PG macromolecule with random branch-on-branch topology. In addition, ketones, benzyl esters and aromatic ethers are found not to react with glycidol even in the presence of GO, while the aldehydes are easily oxidized into carboxyl groups under ambient condition, behaving then as the carboxyl groups. Our findings pose the foundation for understanding the polymerization mechanism of PG on CNMs. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0021-9606 159 19 2023 Efficiency and energy balance for substitution of CH4 in clathrate hydrates with CO2 under multiple-phase coexisting conditions 194504 EN Hideki Tanaka Research Institute for Interdisciplinary Science, Okayama University Masakazu Matsumoto Research Institute for Interdisciplinary Science, Okayama University Takuma Yagasaki Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University Many experimental and theoretical studies on CH4–CO2 hydrates have been performed aiming at the extraction of CH4 as a relatively clean energy resource and concurrent sequestration of CO2. However, vague or insufficient characterization of the environmental conditions prevents us from a comprehensive understanding of even equilibrium properties of CH4–CO2 hydrates for this substitution. We propose possible reaction schemes for the substitution, paying special attention to the coexisting phases, the aqueous and/or the fluid, where CO2 is supplied from and CH4 is transferred to. We address the two schemes for the substitution operating in three-phase and two-phase coexistence. Advantages and efficiencies of extracting CH4 in the individual scheme are estimated from the chemical potentials of all the components in all the phases involved in the substitution on the basis of a statistical mechanical theory developed recently. It is found that although substitution is feasible in the three-phase coexistence, its working window in temperature–pressure space is much narrower compared to the two-phase coexistence condition. Despite that the substitution normally generates only a small amount of heat, a large endothermic substitution is suggested in the medium pressure range, caused by the vaporization of liquid CO2 due to mixing with a small amount of the released CH4. This study provides the first theoretical framework toward the practical use of hydrates replacing CH4 with CO2 and serves as a basis for quantitative planning. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0021-9606 161 21 2024 The nature of the hydrophobic interaction varies as the solute size increases from methane’s to C60’s 214501 EN Hidefumi Naito Department of Chemistry, Faculty of Science, Okayama University Tomonari Sumi Department of Chemistry, Faculty of Science, Okayama University Kenichiro Koga Department of Chemistry, Faculty of Science, Okayama University The hydrophobic interaction, often combined with the hydrophilic or ionic interactions, makes the behavior of aqueous solutions very rich and plays an important role in biological systems. Theoretical and computer simulation studies have shown that the water-mediated force depends strongly on the size and other chemical properties of the solute, but how it changes with these factors remains unclear. We report here a computer simulation study that illustrates how the hydrophobic pair interaction and the entropic and enthalpic terms change with the solute size when the solute–solvent weak attractive interaction is unchanged with the solute size. The nature of the hydrophobic interaction changes qualitatively as the solute size increases from that of methane to that of fullerene. The potential of mean force between small solutes has several well-defined extrema, including the third minimum, whereas the potential of mean force between large solutes has the deep contact minimum and the large free-energy barrier between the contact and the water-bilayer separated configurations. The difference in the potential of mean force is related to the differences in the water density, energy, and hydrogen bond number distributions in the vicinity of the pairs of hydrophobic solutes. 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 Evidence for the relocalization of the ribosome-translocon complex as a key event for the emergence of endoplasmic reticulum during eukaryogenesis EN Isaac CARILO Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0947-6539 30 70 2024 MoSe2-Sensitized Water Splitting Assisted by C60-Dendrons on the Basal Surface e202402690 EN Tomoyuki Tajima Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tomoki Matsuura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Arif Efendi Department of Materials Design and Engineering, University of Toyama Mariko Yukimoto Department of Materials Design and Engineering, University of Toyama Yutaka Takaguchi Department of Materials Design and Engineering, University of Toyama To facilitate water splitting using MoSe2 as a light absorber, we fabricated water-dispersible MoSe2/C60-dendron nanohybrids via physical modification of the basal plane of MoSe2. Upon photoirradiation, the mixed-dimension MoSe2/C60 (2D/0D) heterojunction generates a charge-separated state (MoSe2⋅+/C60⋅−) through electron extraction from the exciton in MoSe2 to C60. This process is followed by the hydrogen evolution reaction (HER) from water in the presence of a sacrificial donor (1-benzyl-1,4-dihydronicotinamide) and co-catalyst (Pt-PVP). The apparent quantum yields of the HER were estimated to be 0.06 % and 0.27 % upon photoexcitation at the A- and B-exciton absorption peaks (λmax=800 and 700 nm), respectively. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Effect of Radon Inhalation on Murine Brain Proteins: Investigation Using Proteomic and Multivariate Analyses 387 399 EN Shota Naoe Graduate School of Health Sciences, Okayama University Ayumi Tanaka Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Reiju Takenaka Graduate School of Health Sciences, Okayama University Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Takaaki Miyaji Advanced Science Research Center, Okayama University Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/67663 Radon is a known risk factor for lung cancer; however, it can be used beneficially, such as in radon therapy. We have previously reported the enhancement of antioxidant effects associated with trace amounts of oxidative stress as one of the positive biological effects of radon inhalation. However, the biological effects of radon inhalation are incompletely understood, and more detailed and comprehensive studies are required. Although several studies have used proteomics to investigate the effects of radon inhalation on body proteins, none has focused on brain proteins. In this study, we evaluated the expression status of proteins in murine brains using proteomic and multivariate analyses to identify those whose expressions changed following two days of radon inhalation at a concentration of 1,500 Bq/m3. We found associations of radon inhalation with the expressions of seven proteins related to neurotransmission and heat shock. These proteins may be proposed as biomarkers indicative of radon inhalation. Although further studies are required to obtain the detailed biological significance of these protein alterations, this study contributes to the elucidation of the biological effects of radon inhalation as a low-dose radiation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1618-2642 416 28 2024 Comparison of protein immobilization methods with covalent bonding on paper for paper-based enzyme-linked immunosorbent assay 6679 6686 EN Yang Chen Department of Chemistry, Okayama University Kaewta Danchana Department of Chemistry, Okayama University Takashi Kaneta Department of Chemistry, Okayama University In this study, two methods were examined to optimize the immobilization of antibodies on paper when conducting a paper-based enzyme-linked immunosorbent assay (P-ELISA). Human IgG, as a test-capture protein, was immobilized on paper via the formation of Schiff bases. Aldehyde groups were introduced onto the surface of the paper via two methods: NaIO4 and 3-aminopropyltriethoxysilane (APTS) with glutaraldehyde (APTS-glutaraldehyde). In the assay, horseradish peroxidase-conjugated anti-human IgG (HRP-anti-IgG) binds to the immobilized human IgG, and the colorimetric reaction of 3,3′,5,5′-tetramethylbenzyzine (TMB) produces a blue color in the presence of H2O2 and HRP-anti-IgG as a model analyte. The immobilization of human IgG, the enzymatic reaction conditions, and the reduction of the chemical bond between the paper surface and immobilized human IgG all were optimized in order to improve both the analytical performance and the stability. In addition, the thickness of the paper was examined to stabilize the analytical signal. Consequently, the APTS-glutaraldehyde method was superior to the NaIO4 method in terms of sensitivity and reproducibility. Conversely, the reduction of imine to amine with NaBH4 proved to exert only minimal influence on sensitivity and stability, although it tended to degrade reproducibility. We also found that thick paper was preferential when using P-ELISA because a rigid paper substrate prevents distortion of the paper surface that is often caused by repeated washing processes. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1022-1336 46 1 2024 Elastomer Particle Monolayers Formed by the Compression of Poly(methyl acrylate) Microparticles at an Air/Water Interface 2400604 EN Yuma Sasaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuichiro Nishizawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Natsuki Watanabe Department of Physics, Nagoya University Takayuki Uchihashi Department of Physics, Nagoya University Daisuke Suzuki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University In the previous study (Green Chem., 2023, 25, 3418), highly stretchable and mechanically tough poly(methyl acrylate) (pMA) microparticle-based elastomers can be formed by drying a microparticle-containing aqueous dispersion. This discovery has the potential to overcome the mechanical weakness of industrially produced aqueous latex films. However, in 3D-arranged particle films, structural complexity, such as the existence of defects, makes it difficult to clearly understand the relationship between the particle film structure and its mechanical properties. In this study, 2D-ordered pMA particle monolayers at the air/water interface of a Langmuir trough are prepared. Under high compression at the air/water interface, the microparticles contact their neighboring particles, and the resulting monolayers can be successfully transferred onto a solid substrate. The compression of the monolayer films is linked to an increase in the elastic modulus of the monolayer film on the solid substrate as evident from the local Young's modulus mapping using atomic force microscopy. Thus, pMA particle films with different mechanical properties can be created using a Langmuir trough. No potential conflict of interest relevant to this article was reported.

Beilstein-Institut Acta Medica Okayama 1860-5397 20 2024 Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor 1560 1571 EN Koichi Mitsudo Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Atsushi Osaki Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haruka Inoue Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Eisuke Sato Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Naoki Shida Graduate School of Engineering Science and Advanced Chemical Energy Research Center, Yokohama National University Mahito Atobe Graduate School of Engineering Science and Advanced Chemical Energy Research Center, Yokohama National University Seiji Suga Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University An electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines using a proton-exchange membrane (PEM) reactor was developed. Cyanoarenes were then reduced to the corresponding benzylamines at room temperature in the presence of ethyl phosphate. The reduction of nitroarenes proceeded at room temperature, and a variety of anilines were obtained. The quinoline reduction was efficiently promoted by adding a catalytic amount of p-toluenesulfonic acid (PTSA) or pyridinium p-toluenesulfonate (PPTS). Pyridine was also reduced to piperidine in the presence of PTSA. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 The Role of the Lipid Profile and Oxidative Stress in Fatigue, Sleep Disorders and Cognitive Impairment in Patients with Multiple Sclerosis 259 270 EN Gonul Vural Department of Neurology, Faculty of Medicine, Ankara Yildirim Beyazit University Esra Demir Department of Neurology, Ankara City Hospital Sadiye Gumusyayla Department of Neurology, Faculty of Medicine, Ankara Yildirim Beyazit University Funda Eren Department of Clinical Biochemistry, Ankara City Hospital Serdar Barakli Department of Neurology, Ankara City Hospital Salim Neselioglu Department of Clinical Biochemistry, Ankara City Hospital Ozcan Erel Department of Clinical Biochemistry, Ankara City Hospital Original Article 10.18926/AMO/67201 The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol–disulfide homeostasis with cognitive impairment, fatigue and sleep disorders in patients with multiple sclerosis. The cognitive functions of patients were evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Fatigue was evaluated with the Fatigue Severity Scale and the Fatigue Impact Scale. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were used to assess patients’ sleep disturbance. Peripheral blood samples were collected, and lipid levels and myeloperoxidase and paraoxonase activity were measured. The myeloperoxidase/paraoxonase ratio, which indicates dysfunctional high-density lipoprotein, was calculated. Thiol–disulfide homeostasis and ischaemia-modified albumin were measured.<br> We did not identify any relationship between dysfunctional high-density lipoprotein and the physical disability, cognitive decline, fatigue and sleep problems of multiple sclerosis. Thiol–disulfide homeostasis was associated with cognitive scores. The shift of the balance towards disulfide was accompanied by a decrease in cognitive scores. On the other hand, we did not detect any relationship between fatigue and sleep disorders and thiol–disulfide homeostasis. Our findings revealed a possible correlation between cognitive dysfunction and thiol–disulfide homeostasis in multiple sclerosis patients. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0002-7863 146 22 2024 Skeletal Formation of Carbocycles with CO2: Selective Synthesis of Indolo[3,2-b]carbazoles or Cyclophanes from Indoles, CO2, and Phenylsilane 14935 14941 EN Sha Li Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Shoko Nakahara Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Taishin Adachi Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Takumi Murata Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Kazuto Takaishi Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tadashi Ema Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University The catalytic reactions of indoles with CO2 and phenylsilane afforded indolo[3,2-b]carbazoles, where the fused benzene ring was constructed by forming two C–H bonds and four C–C bonds with two CO2 molecules via deoxygenative conversions. Nine-membered cyclophanes made up of three indoles and three CO2 molecules were also obtained, where the cyclophane framework was constructed by forming six C–H bonds and six C–C bonds. These multicomponent cascade reactions giving completely different carbocycles were switched simply by choosing the solvent, acetonitrile or ethyl acetate. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1932-7447 127 25 2023 Li-Ion Transport and Solution Structure in Sulfolane-Based Localized High-Concentration Electrolytes 12295 12303 EN Taku Sudoh Taku Sudoh Department of Chemistry and Life Science, Yokohama National University Shuhei Ikeda Department of Materials Chemistry, Nagoya University Keisuke Shigenobu Department of Chemistry and Life Science, Yokohama National University Seiji Tsuzuki Advanced Chemical Energy Research Centre (ACERC), Institute of Advanced Sciences, Yokohama National University Kaoru Dokko Department of Chemistry and Life Science, Yokohama National University Masayoshi Watanabe Advanced Chemical Energy Research Centre (ACERC), Institute of Advanced Sciences, Yokohama National University Wataru Shinoda Research Institute for Interdisciplinary Science and Department of Chemistry, Okayama University Kazuhide Ueno Department of Chemistry and Life Science, Yokohama National University Localized high-concentration electrolytes (LHCEs), which are mixtures of highly concentrated electrolytes (HCEs) and non-coordinating diluents, have attracted significant interest as promising liquid electrolytes for next-generation Li secondary batteries, owing to their various beneficial properties both in the bulk and at the electrode/electrolyte interface. We previously reported that the large Li+-ion transference number in sulfolane (SL)-based HCEs, attributed to the unique exchange/hopping-like Li+-ion conduction, decreased upon dilution with the non-coordinating hydrofluoroether (HFE) despite the retention of the local Li+-ion coordination structure. Therefore, in this study, we investigated the effects of HFE dilution on the Li+ transference number and the solution structure of SL-based LHCEs via the analysis of dynamic ion correlations and molecular dynamics simulations. The addition of HFE caused nano-segregation in the SL-based LHCEs to afford polar and nonpolar domains and fragmentation of the polar ion-conducting pathway into smaller clusters with increasing HFE content. Analysis of the dynamic ion correlations revealed that the anti-correlated Li+–Li+ motions were more pronounced upon HFE addition, suggesting that the Li+ exchange/hopping conduction is obstructed by the non-ion-conducting HFE-rich domains. Thus, the HFE addition affects the entire solution structure and ion transport without significantly affecting the local Li+-ion coordination structure. Further studies on ion transport in LHCEs would help obtain a design principle for liquid electrolytes with high ionic conductivity and large Li+-ion transference numbers. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0021-9606 160 14 2024 Analysis on high-resolution spectrum of the S1–S0 transition of free-base phthalocyanine 144304 EN Yuki Miyamoto Research Institute for Interdisciplinary Science, Okayama University Ayami Hiramoto Research Institute for Interdisciplinary Science, Okayama University Kana Iwakuni Institute for Laser Science, University of Electro-Communications Susumu Kuma Atomic, Molecular and Optical Physics Laboratory, RIKEN Katsunari Enomoto Department of Physics, University of Toyama Naofumi Nakayama CONFLEX Corporation Masaaki Baba Molecular Photoscience Research Center, Kobe University A high-resolution absorption spectrum of the S-1-S-0 transition of free-base phthalocyanine was observed and analyzed with improved reliability. The spectrum, with a partially resolved rotational structure, was obtained by using the buffer-gas cooling technique and a single-mode tunable laser. Our new analysis reveals that the S-1 <- S-0 0(0)(0) band belongs to the a-type transition, where the electronic transition moment aligns parallel to the NH-HN direction, allowing the assignment of the S-1 state to B-1(3u). These results agree with a prior study using supersonic expansion and are well supported by theoretical calculations. Interestingly, the rotational constant B in the S-1 state, which is often smaller than that in the ground state for typical molecules, was found to be slightly larger than that in the S-0 (1)A(g) state. This suggests a change in the character of pi bonds with the electronic excitation. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1359-6640 249 2024 How do water-mediated interactions and osmotic second virial coefficients vary with particle size? 440 452 EN Hidefumi Naito Department of Chemistry, Faculty of Science, Okayama University Tomonari Sumi Department of Chemistry, Faculty of Science, Okayama University Kenichiro Koga Department of Chemistry, Faculty of Science, Okayama University We examine quantitatively the solute-size dependences of the effective interactions between nonpolar solutes in water and in a simple liquid. The potential w(r) of mean force and the osmotic second virial coefficients B are calculated with high accuracy from molecular dynamics simulations. As the solute diameter increases from methane's to C60's with the solute–solute and solute–solvent attractive interaction parameters fixed to those for the methane–methane and methane–water interactions, the first minimum of w(r) lowers from −1.1 to −4.7 in units of the thermal energy kT. Correspondingly, the magnitude of B (<0) increases proportional to σα with some power close to 6 or 7, which reinforces the solute-size dependence of B found earlier for a smaller range of σ [H. Naito, R. Okamoto, T. Sumi and K. Koga, J. Chem. Phys., 2022, 156, 221104]. We also demonstrate that the strength of the attractive interactions between solute and solvent molecules can qualitatively change the characteristics of the effective pair interaction between solute particles, both in water and in a simple liquid. If the solute–solvent attractive force is set to be weaker (stronger) than a threshold, the effective interaction becomes increasingly attractive (repulsive) with increasing solute size. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 The Roles of Neuropeptide Y in Respiratory Disease Pathogenesis via the Airway Immune Response 95 106 EN Junko Itano Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital Review 10.18926/AMO/66912 The lungs are very complex organs, and the respiratory system performs the dual roles of repairing tissue while protecting against infection from various environmental stimuli. Persistent external irritation disrupts the immune responses of tissues and cells in the respiratory system, ultimately leading to respiratory disease. Neuropeptide Y (NPY) is a 36-amino-acid polypeptide and a neurotransmitter that regulates homeostasis. The NPY receptor is a seven-transmembrane-domain G-protein-coupled receptor with six subtypes (Y1, Y2, Y3, Y4, Y5, and Y6). Of these receptors, Y1, Y2, Y4, and Y5 are functional in humans, and Y1 plays important roles in the immune responses of many organs, including the respiratory system. NPY and the Y1 receptor have critical roles in the pathogenesis of asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. The effects of NPY on the airway immune response and pathogenesis differ among respiratory diseases. This review focuses on the involvement of NPY in the airway immune response and pathogenesis of various respiratory diseases. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0021-9606 160 9 2024 GenIce-core: Efficient algorithm for generation of hydrogen-disordered ice structures 094101 EN Masakazu Matsumoto Research Institute for Interdisciplinary Science, Okayama University Takuma Yagasaki Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University Hideki Tanaka Toyota Physical and Chemical Research Institute Ice is different from ordinary crystals because it contains randomness, which means that statistical treatment based on ensemble averaging is essential. Ice structures are constrained by topological rules known as the ice rules, which give them unique anomalous properties. These properties become more apparent when the system size is large. For this reason, there is a need to produce a large number of sufficiently large crystals that are homogeneously random and satisfy the ice rules. We have developed an algorithm to quickly generate ice structures containing ions and defects. This algorithm is provided as an independent software module that can be incorporated into crystal structure generation software. By doing so, it becomes possible to simulate ice crystals on a previously impossible scale. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Role of Macrophages in Liver Fibrosis 1 8 EN Cuiming Sun Department of Pathology and Experimental Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Matsukawa Department of Pathology and Experimental Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/66664 Liver fibrosis, which ultimately leads to liver cirrhosis and hepatocellular carcinoma, is a major health burden worldwide. The progression of liver fibrosis is the result of the wound-healing response of liver to repeated injury. Hepatic macrophages are cells with high heterogeneity and plasticity and include tissue-resident macrophages termed Kupffer cells, and recruited macrophages derived from circulating monocytes, spleen and peritoneal cavity. Studies have shown that hepatic macrophages play roles in the initiation and progression of liver fibrosis by releasing inflammatory cytokines/chemokines and pro-fibrogenic factors. Furthermore, the development of liver fibrosis has been shown to be reversible. Hepatic macrophages have been shown to alternately regulate both the regression and turnover of liver fibrosis by changing their phenotypes during the dynamic progression of liver fibrosis. In this review, we summarize the role of hepatic macrophages in the progression and regression of liver fibrosis. 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.

American Chemical Society (ACS) Acta Medica Okayama 1549-9596 64 2 2023 pSPICA Force Field Extended for Proteins and Peptides 532 542 EN Yusuke Miyazaki Research Institute for Interdisciplinary Science, Okayama University Wataru Shinoda Research Institute for Interdisciplinary Science, Okayama University Many coarse-grained (CG) molecular dynamics (MD) studies have been performed to investigate biological processes involving proteins and lipids. CG force fields (FFs) in these MD studies often use implicit or nonpolar water models to reduce computational costs. CG-MD using water models cannot properly describe electrostatic screening effects owing to the hydration of ionic segments and thus cannot appropriately describe molecular events involving water channels and pores through lipid membranes. To overcome this issue, we developed a protein model in the pSPICA FF, in which a polar CG water model showing the proper dielectric response was adopted. The developed CG model greatly improved the transfer free energy profiles of charged side chain analogues across the lipid membrane. Application studies on melittin-induced membrane pores and mechanosensitive channels in lipid membranes demonstrated that CG-MDs using the pSPICA FF correctly reproduced the structure and stability of the pores and channels. Furthermore, the adsorption behavior of the highly charged nona-arginine peptides on lipid membranes changed with salt concentration, indicating the pSPICA FF is also useful for simulating protein adsorption on membrane surfaces. 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.

Wiley Acta Medica Okayama 1434-193X 26 47 2023 Electrochemical Coupling Reactions Using Non‐Transition Metal Mediators: Recent Advances e202300835 EN Koichi Mitsudo Division of Applied Chemistry Graduate School of Environmental Life, Natural Science and Technology, Okayama University Yasuyuki Okumura Division of Applied Chemistry Graduate School of Environmental Life, Natural Science and Technology, Okayama University Eisuke Sato Division of Applied Chemistry Graduate School of Environmental Life, Natural Science and Technology, Okayama University Seiji Suga Division of Applied Chemistry Graduate School of Environmental Life, Natural Science and Technology, Okayama University Indirect electrolysis method using appropriate mediators enables numerous chemical reactions. The general principles of mediators were described herein with a particular focus on non-transition metal mediators. Recent representative examples of bond formation reactions by indirect electrolysis are summarized and discussed here. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0022-2623 65 8 2022 Identification of a Vitamin-D Receptor Antagonist, MeTC7, which Inhibits the Growth of Xenograft and Transgenic Tumors In Vivo 6039 6055 EN Negar Khazan Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Kyu Kwang Kim Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Jeanne N. Hansen Department of Pediatrics, University of Rochester Medical Center Niloy A. Singh Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Taylor Moore Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Cameron W. A. Snyder Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Ravina Pandita Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Myla Strawderman Department of Biostatistics and Computational Biology, University of Rochester Medical Center Michiko Fujihara Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Takamura Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ye Jian Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Nicholas Battaglia Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Naohiro Yano Department of Surgery, Division of Surgical Research, Rhode Island Hospital, Alpert Medical School of Brown University Yuki Teramoto Department of Pathology and Laboratory Medicine, University of Rochester Medical Center Leggy A. Arnold Department of Chemistry and Biochemistry, University of Wisconsin Milwaukee Russell Hopson Department of Chemistry, Brown University Keshav Kishor Department of Chemistry, Birla Institute of Technology Sneha Nayak Department of Chemistry, Birla Institute of Technology Debasmita Ojha Department of Chemistry, Birla Institute of Technology Ashoke Sharon Department of Chemistry, Birla Institute of Technology John M. Ashton Genomics Core Facility, Wilmot Cancer Center, University of Rochester Medical Center Jian Wang Department of Pharmacology and Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Penn State University Michael T. Milano Department of Radiation Oncology, University of Rochester Medical Center Hiroshi Miyamoto Department of Pathology and Laboratory Medicine, University of Rochester Medical Center David C. Linehan Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Scott A. Gerber Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Nada Kawar Center for Breast Health and Gynecologic Oncology, Mercy Medical Center Ajay P. Singh Rutgers, The State University of New Jersey Erdem D. Tabdanov CytoMechanobiology Laboratory, Department of Pharmacology, Penn State College of Medicine, Pennsylvania State University Nikolay V. Dokholyan Department of Pharmacology and Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Penn State University Hiroki Kakuta Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Peter W. Jurutka School of Mathematical and Natural Sciences, Arizona State University, Health Futures Center Nina F. Schor Departments of Pediatrics, Neurology, and Neuroscience, University of Rochester Medical Center Rachael B. Rowswell-Turner Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Rakesh K. Singh Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Richard G. Moore Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Vitamin-D receptor (VDR) mRNA is overexpressed in neuroblastoma and carcinomas of lung, pancreas, and ovaries and predicts poor prognoses. VDR antagonists may be able to inhibit tumors that overexpress VDR. However, the current antagonists are arduous to synthesize and are only partial antagonists, limiting their use. Here, we show that the VDR antagonist MeTC7 (5), which can be synthesized from 7-dehydrocholesterol (6) in two steps, inhibits VDR selectively, suppresses the viability of cancer cell-lines, and reduces the growth of the spontaneous transgenic TH-MYCN neuroblastoma and xenografts in vivo. The VDR selectivity of 5 against RXRα and PPAR-γ was confirmed, and docking studies using VDR-LBD indicated that 5 induces major changes in the binding motifs, which potentially result in VDR antagonistic effects. These data highlight the therapeutic benefits of targeting VDR for the treatment of malignancies and demonstrate the creation of selective VDR antagonists that are easy to synthesize. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Association of Tumor Necrosis Factor-Alpha with Psychopathology in Patients with Schizophrenia 395 405 EN Marko Pavlovic University Hospital Center Mostar, University of Mostar Dragan Babic University Hospital Center Mostar, University of Mostar Pejana Rastovic University Hospital Center Mostar, University of Mostar Jurica Arapovic University Hospital Center Mostar, University of Mostar Marko Martinac Health Care Center Mostar, University of Mostar Sanja Jakovac University Hospital Center Mostar, University of Mostar Romana Barbaric University Hospital Center Mostar, University of Mostar Original Article 10.18926/AMO/65750 We investigated the relationship between serum tumor necrosis factor-alpha (TNF-α) levels and psychopathological symptoms, clinical and socio-demographic characteristics and antipsychotic therapy in individuals with schizophrenia. TNF-α levels were measured in 90 patients with schizophrenia and 90 healthy controls matched by age, gender, smoking status, and body mass index. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychopathology in patients. No significant differences in TNF-α levels were detected between the patients and controls (p=0.736). TNF-α levels were not correlated with total, positive, negative, general, or composite PANSS scores (all p>0.05). A significant negative correlation was observed between TNF-α levels and the PANSS cognitive factor (ρ=−0.222, p=0.035). A hierarchical regression analysis identified the cognitive factor as a significant predictor of the TNF-α level (beta=−0.258, t=−2.257, p=0.027). There were no significant differences in TNF-α levels among patients treated with different types of antipsychotics (p=0.596). TNF-α levels correlated positively with the age of onset (ρ=0.233, p=0.027) and negatively with illness duration (ρ=−0.247, p=0.019) and antipsychotic treatment duration (ρ=−0.256, p=0.015). These results indicate that TNF-α may be involved in cognitive impairment in schizophrenia, and would be a potential clinical-state marker in schizophrenia. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Association between Radon Hot Spring Bathing and Health Conditions: A Cross-Sectional Study in Misasa, Japan 387 394 EN Takahiro Kataoka Department of Radiological Technology, Okayama University Graduate School of Health Sciences Hiroshi Habu Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayumi Tanaka Department of Radiological Technology, Okayama University Graduate School of Health Sciences Shota Naoe Department of Radiological Technology, Okayama University Graduate School of Health Sciences Kaito Murakami Department of Radiological Technology, Okayama University Graduate School of Health Sciences Yuki Fujimoto Department of Radiological Technology, Okayama University Graduate School of Health Sciences Ryohei Yukimine Department of Radiological Technology, Okayama University Graduate School of Health Sciences Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumihiro Mitsunobu Department of Longevity and Social Medicine (Geriatrics), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyonori Yamaoka Department of Radiological Technology, Okayama University Graduate School of Health Sciences Original Article 10.18926/AMO/65749 No epidemiological studies have examined the health effects of daily bathing in radon hot springs. In this cross-sectional study, we investigated the associations between radon hot spring bathing and health conditions. The target population was 5,250 adults ≥ 20 years old in the town of Misasa, Japan. We collected information about the participants’ bathing habits and alleviation of a variety of disease symptoms, and their self-rated health (SRH). Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated. In both the adjusted and unadjusted models of hypertension, significant associations between the > 1×/week hot spring bathing and the alleviation of hypertension symptoms were observed compared to the group whose hot spring bathing was <1×/week: adjusted model, OR 5.40 (95%CI: 1.98-14.74); unadjusted model, 3.67 (1.50-8.99) and for gastroenteritis: adjusted model, 9.18 (1.15-72.96); unadjusted model, 7.62 (1.59-36.49). Compared to the no-bathing group, higher SRH was significantly associated with both bathing < 1×/week: unadjusted model, 2.27 (1.53-3.37) and > 1×/week: adjusted model, 1.91 (1.15-3.19). These findings suggest that bathing in radon hot springs is associated with higher SRH and the alleviation of hypertension and gastroenteritis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Changes in TRPV1 Receptor, CGRP, and BDNF Expression in Rat Dorsal Root Ganglion with Resiniferatoxin-Induced Neuropathic Pain: Modulation by Pulsed Radiofrequency Applied to the Sciatic Nerve 359 364 EN Tomohiro Koshida Department of Anesthesiology and Pain Clinic, Faculty of Medicine, University of Miyazaki Toyoaki Maruta Department of Anesthesiology and Pain Clinic, Faculty of Medicine, University of Miyazaki Nobuhiko Tanaka Tanaka homecare clinic Kotaro Hidaka Department of Anesthesiology and Pain Clinic, Faculty of Medicine, University of Miyazaki Mio Kurogi Department of Anesthesiology and Pain Clinic, Faculty of Medicine, University of Miyazaki Takayuki Nemoto Department of Pharmacology, Faculty of Medicine, Fukuoka University Toshihiko Yanagita Department of Clinical Pharmacology, School of Nursing, Faculty of Medicine, University of Miyazaki Ryu Takeya Department of Pharmacology, Faculty of Medicine, University of Miyazaki Isao Tsuneyoshi Department of Anesthesiology and Pain Clinic, Faculty of Medicine, University of Miyazaki Original Article 10.18926/AMO/65741 Pulsed radiofrequency (PRF) is a safe method of treating neuropathic pain by generating intermittent electric fields at the needle tip. Resiniferatoxin (RTX) is an ultrapotent agonist of transient receptor potential vanilloid subtype-1 (TRPV1) receptors. We investigated the mechanism of PRF using a rat model of RTX-induced neuropathic pain. After administering RTX intraperitoneally, PRF was applied to the right sciatic nerve. We observed the changes in TRPV1, calcitonin gene-related peptide (CGRP), and brain-derived neurotrophic factor (BDNF) in the dorsal root ganglia by western blotting. Expressions of TRPV1 and CGRP were significantly lower in the contralateral (RTX-treated, PRF-untreated) tissue than in control rats (p<0.0001 and p<0.0001, respectively) and the ipsilateral tissues (p<0.0001 and p<0.0001, respectively). BDNF levels were significantly higher in the contralateral tissues than in the control rats (p<0.0001) and the ipsilateral tissues (p<0.0001). These results suggest that, while TRPV1 and CGRP are decreased by RTX-induced neuronal damage, increased BDNF levels result in pain development. PRF may promote recovery from neuronal damage with concomitant restoration of TRPV1 and CGRP, and exert its analgesic effect by reversing BDNF increase. Further research is required to understand the role of TRPV1 and CGRP restoration in improving mechanical allodynia. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0342-1791 50 3 2023 Sound velocity and elastic properties of Fe–Ni–S–Si liquid: the effects of pressure and multiple light elements 19 EN Iori Yamada Department of Earth and Space Science, Osaka University Hidenori Terasaki Department of Earth Sciences, Okayama University Satoru Urakawa Department of Earth Sciences, Okayama University Tadashi Kondo Department of Earth and Space Science, Osaka University Akihiko Machida Synchrotron Radiation Research Center, National Institutes for Quantum Science and Technology (QST) Yoshinori Tange Japan Synchrotron Radiation Research Institute Yuji Higo Japan Synchrotron Radiation Research Institute Fe–Ni–S–Si alloy is considered to be one of the plausible candidates of Mercury core material. Elastic properties of Fe–Ni–S–Si liquid are important to reveal the density profile of the Mercury core. In this study, we measured the P-wave velocity (VP) of Fe–Ni–S–Si (Fe73Ni10S10Si7, Fe72Ni10S5Si13, and Fe67Ni10S10Si13) liquids up to 17 GPa and 2000 K to study the effects of pressure, temperature, and multiple light elements (S and Si) on the VP and elastic properties.<br> The VP of Fe–Ni–S–Si liquids are less sensitive to temperature. The effect of pressure on the VP are close to that of liquid Fe and smaller than those of Fe–Ni–S and Fe–Ni–Si liquids. Obtained elastic properties are KS0 = 99.1(9.4) GPa, KS’ = 3.8(0.1) and ρ0 =6.48 g/cm3 for S-rich Fe73Ni10S10Si7 liquid and KS0 = 112.1(1.5) GPa, KS’ = 4.0(0.1) and ρ0=6.64 g/cm3 for Si-rich Fe72Ni10S5Si13 liquid. The VP of Fe–Ni–S–Si liquids locate in between those of Fe–Ni–S and Fe–Ni–Si liquids. This suggests that the effect of multiple light element (S and Si) on the VP is suppressed and cancel out the effects of single light elements (S and Si) on the VP. The effect of composition on the EOS in the Fe–Ni–S–Si system is indispensable to estimate the core composition combined with the geodesy data of upcoming Mercury mission. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Brown Adipose Tissue PPARγ Is Required for the Insulin-Sensitizing Action of Thiazolidinediones 243 254 EN Yusuke Shibata Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, 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 Original Article 10.18926/AMO/65489 Brown adipose tissue (BAT) plays a critical role in metabolic homeostasis. BAT dysfunction is associated with the development of obesity through an imbalance between energy expenditure and energy intake. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is the master regulator of adipogenesis. However, the roles of PPARγ and thiazolidinediones (TZDs) in the regulation of BAT metabolism remain unclear. TZDs, which are selective PPARγ activators, improve systemic insulin resistance in animals and humans. In the present study, we generated brown adipocyte-specific PPARγ-deficient mice (BATγKO) to examine the in vivo roles of PPARγ and TZDs in BAT metabolism. In electron microscopic examinations, brown adipocyte-specific PPARγ deletion promoted severe whitening of brown fat and morphological alteration of mitochondria. Brown adipocyte-specific PPARγ deletion also reduced mRNA expression of BAT-selective genes. Although there was no difference in energy expenditure between control and BATγKO mice in calorimetry, norepinephrine-induced thermogenesis was impaired in BATγKO mice. Moreover, pioglitazone treatment improved diet-induced insulin resistance in the control mice but not in the BATγKO mice. These findings suggest that BAT PPARγ is necessary for the maintenance of brown adipocyte function and for the insulin-sensitizing action of TZDs. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Immediate soft-tissue adhesion and the mechanical properties of the Ti–6Al–4V alloy after long-term acid treatment EN Yaming Wang Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Important roles of odontoblast membrane phospholipids in early dentin mineralization EN Risa ANADA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1755-4330 15 5 2023 Catalytic enantioselective nucleophilic desymmetrization of phosphonate esters 714 721 EN Michele Formica Chemistry Research Laboratory, Department of Chemistry, University of Oxford Tatiana Rogova Chemistry Research Laboratory, Department of Chemistry, University of Oxford Heyao Shi Chemistry Research Laboratory, Department of Chemistry, University of Oxford Naoto Sahara Chemistry Research Laboratory, Department of Chemistry, University of Oxford Branislav Ferko Chemistry Research Laboratory, Department of Chemistry, University of Oxford Alistair J. M. Farley Chemistry Research Laboratory, Department of Chemistry, University of Oxford Kirsten E. Christensen Chemistry Research Laboratory, Department of Chemistry, University of Oxford Fernanda Duarte Chemistry Research Laboratory, Department of Chemistry, University of Oxford Ken Yamazaki Division of Applied Chemistry, Okayama University Darren J. Dixon Chemistry Research Laboratory, Department of Chemistry, University of Oxford Molecules that contain a stereogenic phosphorus atom are crucial to medicine, agrochemistry and catalysis. While methods are available for the selective construction of various chiral organophosphorus compounds, catalytic enantioselective approaches for their synthesis are far less common. Given the vastness of possible substituent combinations around a phosphorus atom, protocols for their preparation should also be divergent, providing facile access not only to one but to many classes of phosphorus compounds. Here we introduce a catalytic and enantioselective strategy for the preparation of an enantioenriched phosphorus(V) centre that can be diversified enantiospecifically to a wide range of biologically relevant phosphorus(V) compounds. The process, which involves an enantioselective nucleophilic substitution catalysed by a superbasic bifunctional iminophosphorane catalyst, can accommodate a wide range of carbon substituents at phosphorus. The resulting stable, yet versatile, synthetic intermediates can be combined with a multitude of medicinally relevant O-, N- and S-based nucleophiles. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 Graphene Oxide-based Endodontic Sealer: An in Vitro Study 715 721 EN Mohammed Zahedul Islam Nizami Department of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Melahat Gorduysus Department of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Shinoda-Ito Department of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto Department of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuta Nishina Research Core for Interdisciplinary Sciences, Okayama University Shogo Takashiba Research Core for Interdisciplinary Sciences, Okayama University Zulema Arias Department of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Original Article 10.18926/AMO/64122 The failure of endodontic treatment is directly associated with microbial infection in the root canal or periapical areas. An endodontic sealer that is both bactericidal and biocompatible is essential for the success of root canal treatments. This is one of the vital issues yet to be solved in clinical dental practice. This in vitro study assessed the effectiveness of graphene oxide (GO) composites GO-CaF2 and GO-Ag-CaF2 as endodontic sealer materials. Dentin slices were coated with either the GO-based composites or commonly used root canal sealers (non-eugenol zinc oxide sealer). The coated slices were treated in 0.9% NaCl, phosphate-buffered saline (PBS), and simulated body fluid (SBF) at 37˚C for 24 hours to compare their sealing effect on the dentin surface. In addition, the radiopacity of these composites was examined to assess whether they complied with the requirements of a sealer for good radiographic visualization. Scanning electron microscopy showed the significant sealing capability of the composites as coating materials. Radiographic images confirmed their radiopacity. Mineral deposition indicated their bioactivity, especially of GO-Ag-CaF2, and thus it is potential for regenerative application. They were both previously shown to be bactericidal to oral microbes and cytocompatible with host cells. With such a unique assemblage of critical properties, these GO-based composites show promise as endodontic sealers for protection against reinfection in root canal treatment and enhanced success in endodontic treatment overall. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients 661 671 EN Yuko Abe Department of Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruto Taira Department of Breast and Endocrine surgery, Kawasaki Medical School Hospital Kosuke Kashiwabara Clinical Research Promotion Center, University of Tokyo Hospital Junji Tsurutani Advanced Cancer Translational Research Institute, Showa University Masahiro Kitada Breast Disease Center, Asahikawa Medical University Hospital Masato Takahashi Department of Breast Surgery, National Hospital Organization Hokkaido Cancer Center Hiroaki Kato Department of Breast Surgery, Teine Keijinkai Hospital Yuichiro Kikawa Department of Breast Surgery, Kansai Medical University Hospital Eiko Sakata Department of Breast Surgery, Niigata City General Hospital Yoichi Naito Department of Medical Oncology, National Cancer Center Hospital East Yoshie Hasegawa Department of Breast Surgery, Hachinohe City Hospital Tsuyoshi Saito Department of Breast Surgery, Japanese Red Cross Saitama Hospital Tsutomu Iwasa Department of Medical Oncology, Kindai University Faculty of Medicine Tsutomu Takashima Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine Tomohiko Aihara Breast Center, Aihara Hospital Hirofumi Mukai Department of Medical Oncology, National Cancer Center Hospital East Fumikata Hara Breast Oncology Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research Tadahiko Shien Department of Breast and Endocrine surgery, Okayama University Hospital Hiroyoshi Doihara Department of Breast surgery, Kawasaki Medical School General Medical Center Shinichi Toyooka Department of Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/64116 Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients’ quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001−3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01). No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Viral Sequences Are Repurposed for Controlling Antiviral Responses as Non-Retroviral Endogenous Viral Elements 503 510 EN Hirohito Ogawa Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoyuki Honda Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Review 10.18926/AMO/64025 Eukaryotic genomes contain numerous copies of endogenous viral elements (EVEs), most of which are considered endogenous retrovirus (ERV) sequences. Over the past decade, non-retroviral endogenous viral elements (nrEVEs) derived from ancient RNA viruses have been discovered. Several functions have been proposed for these elements, including antiviral defense. This review summarizes the current understanding of nrEVEs derived from RNA viruses, particularly endogenous bornavirus-like elements (EBLs) and endogenous filovirus-like elements (EFLs). EBLs are one of the most extensively studied nrEVEs. The EBL derived from bornavirus nucleoprotein (EBLN) is thought to function as a non-coding RNA or protein that regulates host gene expression or inhibits virus propagation. Ebolavirus and marburgvirus, which are filoviruses, induce severe hemorrhagic fever in humans and nonhuman primates. Although the ecology of filoviruses remains unclear, bats are believed to be potential reservoirs. Based on the knowledge from EBLs, it is postulated that EFLs in the bat genome help to maintain the balance between filovirus infection and the bat’s defense system, which may partially explain why bats act as potential reservoirs. Further research into the functions of nrEVEs could reveal novel antiviral systems and inspire novel antiviral approaches. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0021-9797 629 2023 Acidic layer-enhanced nanoconfinement of anions in cylindrical pore of single-walled carbon nanotube 238 244 EN Takahiro Ohkubo Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Hiroki Nakayasu Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Yuki Takeuchi Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Nobuyuki Takeyasu Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Yasushige Kuroda Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University The adsorption of the nitrate ion by the cylindrical pore of single-walled carbon nanotubes (SWCNT) was found to be aided by an acidic adsorbed layer. Adsorbed water in the vicinity of the pore wall can supply protons through ionization, forming the acidic layer, according to Raman spectra and results of solution pH fluctuations caused by ion species adsorption. Such an acidic adsorbed layer leads to surplus adsorption of anionic species where the adsorbed amount of nitrate ions is much larger than that of cations. Also, we could observe the Raman bands being assignable to the symmetrical stretching mode at an extremely highfrequency region for nano-restricted nitrate ions compared to any other bulk phases. The abnormal band shift of adsorbed nitrate ions indicates that the nitrate ions are confined in the pore under the effects of nanoconfinement by the pore and the strong interaction with the acidic layer in the pore. Our results warn that we have to construct the adsorption model of aqueous electrolytes confined in carbon pores by deliberating the acid layer formed by the adsorbed water. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Elucidation of the Mechanism and Significance of the Erythrocyte Sedimentation Rate from Clinical Laboratory Data 447 455 EN Hiroshi Umemura Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine Yoshiaki Fukuda Department of Clinical Laboratory, Nihon University Itabashi Hospital Tetsuo Miyashita Department of Clinical Laboratory, Nihon University Itabashi Hospital Tomohiro Nakayama Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine Original Article 10.18926/AMO/63904 The erythrocyte sedimentation rate (ESR) is a widely used marker of inflammation, but the detailed mechanisms underlying the ESR remain unclear. We retrospectively collected laboratory data from our hospital’s laboratory information system, and performed multiple linear regression analysis and correlation analysis to determine relationships between the ESR and other laboratory test parameters. The alpha-2, beta-2, and gamma fractions from serum protein electrophoresis, serum immunoglobulin (Ig) G, IgA, IgM, and complement C3 levels, plasma fibrinogen levels, and platelet count showed positive effects on the ESR; however, the serum albumin level showed negative effects. Since erythrocytes are negatively charged, an increase in positively charged proteins and a decrease in negatively charged albumin were suggested to increase the ESR. Notably, C-reactive protein (CRP) showed the third-strongest correlation with the ESR despite having no significant effect on the ESR. We also reviewed cases with discordant ESR and CRP levels to compare the disease profiles of high ESR/low CRP patients and low ESR/high CRP patients. The patients with high ESR/low CRP had a completely different disease profile from those with low ESR/high CRP. Since the ESR and CRP have different roles, they should be used as markers in a context-dependent manner. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Central and Enteric Neuroprotective Effects by Eucommia ulmoides Extracts on Neurodegeneration in Rotenone-induced Parkinsonian Mouse 373 383 EN Fuminori Imafuku Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jin Sun Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sunao Kamimai Department of Medical Neurobiology, Okayama University Medical School Takashi Shimizu Department of Medical Neurobiology, Okayama University Medical School Toshiaki Toyota Department of Medical Neurobiology, Okayama University Medical School Yusei Okamoto Department of Medical Neurobiology, Okayama University Medical School Nami Isooka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Kikuoka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Kitamura Department of Pharmacy, Okayama University Hospital Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63889 Parkinson’s disease (PD) is a progressive neurodegenerative disease of both the central and peripheral / enteric nervous systems. Oxidative stress and neuroinflammation are associated with the pathogenesis of PD, suggesting that anti-oxidative and anti-inflammatory compounds could be neuroprotective agents for PD. Eucommia ulmoides (EU) is a traditional herbal medicine which exerts neuroprotective effects by anti-inflammatory and anti-oxidative properties. Our previous study showed that treatment with chlorogenic acid, a component of EU, protected against neurodegeneration in the central and enteric nervous systems in a PD model. In this study, we examined the effects of EU extract (EUE) administration on dopaminergic neurodegeneration, glial response and α-synuclein expression in the substantia nigra pars compacta (SNpc), and intestinal enteric neurodegeneration in low-dose rotenone-induced PD model mice. Daily oral administration of EUE ameliorated dopaminergic neurodegeneration and α-synuclein accumulation in the SNpc. EUE treatment inhibited rotenone- induced decreases in the number of total astrocytes and in those expressing the antioxidant molecule metallothionein. EUE also prevented rotenone-induced microglial activation. Furthermore, EUE treatment exerted protective effects against intestinal neuronal loss in the PD model. These results suggest that EU exerts neuroprotective effects in the central and enteric nervous systems of rotenone-induced parkinsonism mice, in part by glial modification. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Therapeutic Approaches Targeting miRNA in Systemic Lupus Erythematosus 359 371 EN Sumie Hiramatsu-Asano Department of Nephrology, Rheumatology, Endocrinology and Metabolism, 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 Review 10.18926/AMO/63887 Systemic lupus erythematosus (SLE) is a potentially fatal systemic autoimmune disease, and its etiology involves both genetic and environmental factors such as sex hormone imbalance, genetic predisposition, epigenetic regulation, and immunological factors. Dysregulation of microRNA (miRNA) is suggested to be one of the epigenetic factors in SLE. miRNA is a 22-nucleotide single-stranded noncoding RNA that contributes to post-transcriptional modulation of gene expression. miRNA targeting therapy has been suggested to be useful for the treatment of cancers and other diseases. Gene knockout and miRNA targeting therapy have been demonstrated to improve SLE disease activity in mice. However, these approaches have not yet reached the level of clinical application. miRNA targeting therapy is limited by the fact that each miRNA has multiple targets. In addition, the expression of certain miRNAs may differ among cell tissues within a single SLE patient. This limitation can be overcome by targeted delivery and chemical modifications. In the future, further research into miRNA chemical modifications and delivery systems will help us develop novel therapeutic agents for SLE. No potential conflict of interest relevant to this article was reported.

ROYAL SOC CHEMISTRY Acta Medica Okayama 2041-6520 13 2022 Annulative coupling of vinylboronic esters: aryne-triggered 1,2-metallate rearrangement 9580 9585 EN Haruki Mizoguchi Graduate School of Natural Science and Technology, Okayama University Hidetoshi Kamada Graduate School of Natural Science and Technology, Okayama University Kazuki Morimoto Graduate School of Natural Science and Technology, Okayama University Ryuji Yoshida Graduate School of Natural Science and Technology, Okayama University Akira Sakakura Graduate School of Natural Science and Technology, Okayama University A stereoselective annulative coupling of a vinylboronic ester ate-complex with arynes producing cyclic borinic esters has been developed. An annulation reaction that proceeded through the formation of two C-C bonds and a C-B bond was realized by exploiting a 1,2-metallate rearrangement of boronate triggered by the addition of a vinyl group to the strained triple bond of an aryne. The generated aryl anion would then cyclize to a boron atom to complete the annulation cascade. The annulated borinic ester could be converted to boronic acids and their derivatives by oxidation, halogenation, and cross-coupling. Particularly, halogenation and Suzuki-Miyaura coupling proceeded in a site-selective fashion and produced highly substituted alkylboronic acid derivatives. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0021-9606 156 22 2022 Osmotic second virial coefficients for hydrophobic interactions as a function of solute size 221104 EN Hidefumi Naito Department of Chemistry, Faculty of Science, Okayama University Ryuichi Okamoto Department of Chemistry, Faculty of Science, Okayama University Tomonari Sumi Department of Chemistry, Faculty of Science, Okayama University Kenichiro Koga Department of Chemistry, Faculty of Science, Okayama University To gain quantitative insight into how the overall strength of the hydrophobic interaction varies with the molecular size, we calculate osmotic second virial coefficients B for hydrophobic spherical molecules of different diameters σ in water based on molecular simulation with corrections to the finite-size and finite-concentration effects. It is shown that B (&lt;0) changes by two orders of magnitude greater as σ increases twofold and its solute-size dependence is best fit by a power law B ∝ σ<jats:sup> α</jats:sup> with the exponent α ≃ 6, which contrasts with the cubic power law that the second virial coefficients of gases obey. It is also found that values of B for the solutes in a nonpolar solvent are positive but they obey the same power law as in water. A thermodynamic identity for B derived earlier [K. Koga, V. Holten, and B. Widom, J. Phys. Chem. B 119, 13391 (2015)] indicates that if B is asymptotically proportional to a power of σ, the exponent α must be equal to or greater than 6. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 1932-7447 126 22 2022 Role of Oxygen Vacancy in the Photocarrier Dynamics of WO3 Photocatalysts: The Case of Recombination Centers 9257 9263 EN Kosaku Kato Graduate School of Natural Science and Technology, Okayama University Yohei Uemura Institute for Molecular Science Kiyotaka Asakura Institute for Catalysis, Hokkaido University Akira Yamakata Graduate School of Natural Science and Technology, Okayama University Defects in powder photocatalysts determine the photocatalytic activity. The addition of defects sometimes enhances the activity, but sometimes decreases it. However, the factors determining the difference between these cases have not been fully elucidated yet. Herein, we investigated the effects of oxygen vacancies on photocarrier dynamics in WO3 powder using broadband transient absorption spectroscopy. It was found that the decay of deeply trapped electrons was accelerated when the number of oxygen vacancies was increased by H-2 reduction. This result suggests that oxygen vacancies in WO3 mainly act as recombination centers. This is in contrast to many other photocatalysts such as TiO2 and SrTiO3, where the carrier lifetime increases with increasing oxygen vacancy concentration. These differences can be attributed to the difference in the distance between oxygen vacancies. When defects are dispersed, trapped electrons need to travel over long distances by repeatedly hopping and tunneling between defects to combine with holes, resulting in decelerated recombination. In contrast, when the defects are connected or located close together, the trapped electrons can readily migrate among defects, leading to enhanced recombination. Control of the distance between defects is thus important for enhancing photocatalytic activity. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0947-6539 28 37 2022 Design and Synthesis of Glycosylated Cholera Toxin B Subunit as a Tracer of Glycoprotein Trafficking in Organelles of Living Cells e202201253 EN Yuta Maki Department of Chemistry, Graduate School of Science, Osaka University Kazuki Kawata Department of Chemistry, Graduate School of Science, Osaka University Yanbo Liu Department of Chemistry, Graduate School of Science, Osaka University Kang‐Ying Goo Department of Chemistry, Graduate School of Science, Osaka University Ryo Okamoto Department of Chemistry, Graduate School of Science, Osaka University Yasuhiro Kajihara Department of Chemistry, Graduate School of Science, Osaka University Ayano Satoh Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Glycosylation of proteins is known to be essential for changing biological activity and stability of glycoproteins on the cell surfaces and in body fluids. Delivering of homogeneous glycoproteins into the endoplasmic reticulum (ER) and the Golgi apparatus would enable us to investigate the function of asparagine-linked (N-) glycans in the organelles. In this work, we designed and synthesized an intentionally glycosylated cholera toxin B-subunit (CTB) to be transported to the organelles of mammalian cells. The heptasaccharide, the intermediate structure of various complex-type N-glycans, was introduced to the CTB. The synthesized monomeric glycosyl-CTB successfully entered mammalian cells and was transported to the Golgi and the ER, suggesting the potential use of synthetic CTB to deliver and investigate the functions of homogeneous N-glycans in specific organelles of living cells. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 Histone Demethylase Jmjd3 Regulates the Osteogenic Differentiation and Cytokine Expressions of Periodontal Ligament Cells 281 290 EN Bo Yu Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease Rui Wang Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease Huikun Luo Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease Di Yang Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease Simo Wang Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease Yaqiong Yu Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease Hirohiko Okamura Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Lihong Qiu Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease Original Article 10.18926/AMO/63722 Periodontal ligament (PDL) cells are critical for the bone remodeling process in periapical lesions since they can differentiate into osteoblasts and secrete osteoclastogenesis-promoting cytokines. Post-translational histone modifications including alterations of the methylation status of H3K27 are involved in cell differentiation and inflammatory reaction. The histone demethylase Jumonji domain-containing 3 (Jmjd3) specifically removes methylation of H3K27. We investigated whether Jmjd3 is involved in the osteogenic differentiation and secretion of PDL cells’ inflammatory factors. Jmjd3 expression in periapical lesions was examined by immunostaining. Using siRNA specific for Jmjd3 or the specific Jmjd3 inhibitor GSK-J4, we determined Jmjd3’s roles in osteogenic differentiation and cytokine production by real-time RT-PCR. The locations of Jmjd3 and NF-κB were analyzed by immunocytochemistry. Compared to healthy PDLs, the periapical lesion samples showed higher Jmjd3 expression. Treatment with GSK-J4 or Jmjd3 siRNA suppressed PDL cells’ osteogenic differentiation by suppressing the expressions of bone-related genes (Runx2, Osterix, and osteocalcin) and mineralization. Jmjd3 knockdown decreased the expressions of cytokines (TNF-α, IL-1β, and IL-6) induced by lipopolysaccharide extracted from Porphyromonas endodontalis (Pe-LPS). Pe-LPS induced the nuclear translocations of Jmjd3 and NF-κB; the latter was inhibited by GSK-J4 treatment. Jmjd3 appears to regulate PDL cells’ osteogenic differentiation and proinflammatory cytokine expressions. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 Intrathecal Administration of the α1 Adrenergic Antagonist Phentolamine Upregulates Spinal GLT-1 and Improves Mirror Image Pain in SNI Model Rats 255 263 EN Kosuke Nakatsuka Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshikazu Matsuoka Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masako Kurita Kinoshita Pain Clinic Ruilin Wang Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chika Tsuboi Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobutaka Sue Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuji Kaku Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63719 Mirror image pain (MIP) is a type of extraterritorial pain that results in contralateral pain or allodynia. Glutamate transporter-1 (GLT-1) is expressed in astrocytes and plays a role in maintaining low glutamate levels in the synaptic cleft. Previous studies have shown that GLT-1 dysfunction induces neuropathic pain. Our previous study revealed bilateral GLT-1 downregulation in the spinal cord of a spared nerve injury (SNI) rat. We hypothesized that spinal GLT-1 is involved in the mechanism of MIP. We also previously demonstrated noradrenergic GLT-1 regulation. Therefore, this study aimed to investigate the effect of an α1 adrenergic antagonist on the development of MIP. Rats were subjected to SNI. Changes in pain behavior and GLT-1 protein levels in the SNI rat spinal cords were then examined by intrathecal administration of the α1 adrenergic antagonist phentolamine, followed by von Frey test and western blotting. SNI resulted in the development of MIP and bilateral downregulation of GLT-1 protein in the rat spinal cord. Intrathecal phentolamine increased contralateral GLT-1 protein levels and partially ameliorated the 50% paw withdrawal threshold in the contralateral hind paw. Spinal GLT-1 upregulation by intrathecal phentolamine ameliorates MIP. GLT-1 plays a role in the development of MIPs. 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.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 2 2022 The Combination of D-dimer and Glasgow Prognostic Score Can Be Useful in Predicting VTE in Patients with Stage IIIC and IVA Ovarian Cancer 129 135 EN Kotaro Kubo Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Okamoto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirofumi Matsuoka Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoyuki Ida Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Haruma Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chikako Ogawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63406 Cancer patients have increased risk of venous thromboembolism (VTE) that must be assessed before treatment. This study aimed to determine effective VTE biomarkers in gynecologic cancer (GC). We investigated the correlation between D-dimer levels, Khorana risk score (KRS), Glasgow prognostic score (GPS), and VTE in 1499 GC patients (583 cervical cancer (CC), 621 endometrial cancer (EC), and 295 ovarian cancer (OC) patients) treated at our institution between January 2008 and December 2019. χ2 and Mann–Whitney U-tests were used to determine statistical significance. We used receiver operating characteristic-curve analysis to evaluate the discriminatory ability of each parameter. D-dimer levels were significantly correlated with KRS and GPS in patients with GC. VTE was diagnosed in 11 CC (1.9%), 27 EC (4.3%), and 39 OC patients (13.2%). Optimal D-dimer cut-off values for VTE were 3.1, 3.2, and 3.9 μg/ml in CC, EC and OC patients, respectively. D-dimer could significantly predict VTE in all GC patients. Furthermore, D-dimer combined with GPS was more accurate in predicting VTE than other VTE biomarkers in stage IIIC and IVA OC (AUC: 0.846; p<0.001). This study demonstrates that combined D-dimer and GPS are useful in predicting VTE in patients with OC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Mouse Model for Optogenetic Genome Engineering 1 5 EN Tomoka Takao Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Yamada Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Takarada Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/63202 Optogenetics, a technology to manipulate biological phenomena thorough light, has attracted much attention in neuroscience. Recently, the Magnet System, a photo-inducible protein dimerization system which can control the intracellular behavior of various biomolecules with high accuracy using light was developed. Furthermore, photoactivation systems for controlling biological phenomena are being developed by combining this technique with genome-editing technology (CRISPR/Cas9 System) or DNA recombination technology (Cre-loxP system). Herein, we review the history of optogenetics and the latest Magnet System technology and introduce our recently developed photoactivatable Cre knock-in mice with temporal-, spatial-, and cell-specific accuracy. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2399-3669 4 1 2021 Kinetics of the ancestral carbon metabolism pathways in deep-branching bacteria and archaea 149 EN Tomonari Sumi Research Institute for Interdisciplinary Science, Okayama University Kouji Harada Department of Computer Science and Engineering, Toyohashi University of Technology The origin of life is believed to be chemoautotrophic, deriving all biomass components from carbon dioxide, and all energy from inorganic redox couples in the environment. The reductive tricarboxylic acid cycle (rTCA) and the Wood-Ljungdahl pathway (WL) have been recognized as the most ancient carbon fixation pathways. The rTCA of the chemolithotrophic Thermosulfidibacter takaii, which was recently demonstrated to take place via an unexpected reverse reaction of citrate synthase, was reproduced using a kinetic network model, and a competition between reductive and oxidative fluxes on rTCA due to an acetyl coenzyme A (ACOA) influx upon acetate uptake was revealed. Avoiding ACOA direct influx into rTCA from WL is, therefore, raised as a kinetically necessary condition to maintain a complete rTCA. This hypothesis was confirmed for deep-branching bacteria and archaea, and explains the kinetic factors governing elementary processes in carbon metabolism evolution from the last universal common ancestor. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 6 2021 EG-VEGF Induces Invasion of a Human Trophoblast Cell Line via PROKR2 677 684 EN Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Mitsui Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakurako Mishima Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Ohira Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jota Maki Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eriko Eto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Hayata Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62806 Extravillous trophoblast (EVT) invasion is important for embryo implantation, placental development, and successful remodeling of the uterine spiral artery. Endocrine gland derived-vascular endothelial growth factor (EG-VEGF) and matrix metalloproteinases (MMPs) are implicated in EVT invasion; however, the high con-centrations found in pregnancy pathologies have not been investigated in non-tumor trophoblasts. The roles of EG-VEGF, prokineticin receptors (PROKR1/2), MMP-2, and MMP-9 in EVT invasion during spiral artery remodeling were evaluated using human EVT from HTR-8/SVneo cell lines. The expression of MMP-2, MMP-9, and mitogen-activated protein kinase (MAPK), and Akt pathways in HTR-8/SVneo cells treated with recom-binant EG-VEGF alongside anti-PROKR1 and/or anti-PROKR2 antibodies was evaluated using quantitative reverse transcription-PCR and western blotting. Wound-healing and cell invasion assays were performed to assess the migration and invasion of these treated cells. Interestingly, 20 nM EG-VEGF activated ERK1/2 sig-naling and upregulated MMP-2 and MMP-9. This effect was suppressed by anti-PROKR2 antibody via ERK1/2 downregulation. Anti-PROKR2 antibody inhibited the migration and invasion of EG-VEGF-stimulated HTR-8/SVneo cells. Elevated concentrations of EG-VEGF enhance EVT invasion in a human trophoblast cell line by upregulating MMP-2 and MMP-9 via PROKR2. These new insights into the regulation of epithelial cell invasion may help in developing therapeutic interventions for placental-related diseases during pregnancy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 6 2021 Multiple Roles of Histidine-Rich Glycoprotein in Vascular Homeostasis and Angiogenesis 671 675 EN Shangze Gao Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Nishibori Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/62805 Histidine-rich glycoprotein (HRG) is a 75 kDa plasma protein that is synthesized in the liver of many verte-brates and present in their plasma at relatively high concentrations of 100-150 μg/mL. HRG is an abundant and well-characterized protein having a multidomain structure that enable it to interact with many ligands, func-tion as an adaptor molecule, and participate in numerous physiological and pathological processes. As a plasma protein, HRG has been reported to regulate vascular biology, including coagulation, fibrinolysis and angiogenesis, through its binding with several ligands (heparin, FXII, fibrinogen, thrombospondin, and plas-minogen) and interaction with many types of cells (endothelial cells, erythrocytes, neutrophils and platelets). This review aims to summarize the roles of HRG in maintaining vascular homeostasis and regulating angiogen-esis in various pathological conditions. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 5 2021 Glial Cells as Possible Targets of Neuroprotection through Neurotrophic and Antioxidative Molecules in the Central and Enteric Nervous Systems in Parkinson’s Disease 549 556 EN Nami Isooka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/62767 Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. The loss of nigrostriatal dopaminergic neurons produces its characteristic motor symptoms, but PD patients also have non-motor symptoms such as constipation and orthostatic hypotension. The pathological hallmark of PD is the presence of α-synuclein-containing Lewy bodies and neurites in the brain. However, the PD pathology is observed in not only the central nervous system (CNS) but also in parts of the peripheral nervous system such as the enteric nervous system (ENS). Since constipation is a typical prodromal non-motor symptom in PD, often preceding motor symptoms by 10-20 years, it has been hypothesized that PD pathology propagates from the ENS to the CNS via the vagal nerve. Discovery of pharmacological and other methods to halt this progression of neurodegeneration in PD has the potential to improve millions of lives. Astrocytes protect neurons in the CNS by secretion of neurotrophic and antioxidative factors. Similarly, astrocyte-like enteric glial cells (EGCs) are known to secrete neuroprotective factors in the ENS. In this article, we summarize the neuroprotective function of astrocytes and EGCs and discuss therapeutic strategies for the prevention of neurodegeneration in PD targeting neurotrophic and antioxidative molecules in glial cells. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 Bendamustine Plus Rituximab as Salvage Treatment for Patients with Relapsed or Refractory Low-grade B-cell Lymphoma and Mantle Cell Lymphoma: A Single-Center Retrospective Study 461 469 EN Hiroyuki Murakami Department of Hematology, National Hospital Organization Okayama Medical Center Takanori Yoshioka Department of Hematology, National Hospital Organization Okayama Medical Center Takashi Moriyama Department of Hematology, National Hospital Organization Okayama Medical Center Tatsunori Ishikawa Department of Hematology, National Hospital Organization Okayama Medical Center Masanori Makita Department of Hematology, National Hospital Organization Okayama Medical Center Kazutaka Sunami Department of Hematology, National Hospital Organization Okayama Medical Center Original Article 10.18926/AMO/62398 Bendamustine plus rituximab (B-R) is an effective therapy for relapsed or refractory (r/r) low-grade B-cell lymphoma (LGBCL) and mantle cell lymphoma (MCL); however, clinical data from Japanese patients treated with B-R therapy are limited. We retrospectively evaluated the efficacy and safety of B-R therapy in 42 patients who received B-R therapy at our hospital for r/r LGBCL and MCL. All patients received intravenous (IV) ritux-imab 375 mg/m2 on day 1 and IV bendamustine 90 mg/m2 on days 2 and 3 every 28 days for up to 6 cycles. The common histologic subtypes were follicular lymphoma (n = 29, 70%), marginal zone lymphoma (n = 6, 14%), and MCL (n = 5, 12%). The overall response rate was 93%, with 62% complete response and complete response unconfirmed. The median progression-free survival (PFS) was 38 months (95% confidence interval [CI], 24.6 to not reached [NR]), and the median overall survival (OS) was 80 months (95% CI, 60.7 to NR). Patients receiving a cumulative dose of bendamustine ≥ 720 mg/m2 showed a significantly longer PFS and OS. Grade 3/4 adverse events (≥ 10%) included neutropenia (55%), lymphopenia (69%), and nausea (24%). B-R therapy was effective and well tolerated, and the cumulative dose of bendamustine was associated with a favorable outcome. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Role of the Transcription Factor BTB and CNC Homology 1 in a Rat Model of Acute Liver Injury Induced by Experimental Endotoxemia 363 372 EN Nohito Tanioka Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroko Shimizu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Emiko Omori Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Takahashi Faculty of Health and Welfare Science, Okayama Prefectural University Masakazu Yamaoka Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62232 Hepatic oxidative stress plays an important role in the pathogenesis of several acute liver diseases, and free heme is thought to contribute to endotoxemia-induced acute liver injury. The heme oxygenase 1 (HO-1) gene is upregulated and the δ-aminolevulinate synthase (ALAS1) gene is downregulated in the rat liver following lipopolysaccharide (LPS) treatment. BTB and CNC homology 1 (Bach1) is a heme-responsive transcription factor that normally represses HO-1 expression. In this study, we evaluated the changes in HO-1, ALAS1, and Bach1 expression and nuclear Bach1 expression in rat livers following intravenous LPS administration (10 mg/kg body weight). LPS significantly upregulated HO-1 mRNA and downregulated ALAS1 mRNA in the rat livers, suggesting that hepatic free heme concentrations are increased after LPS treatment. Bach1 mRNA was strongly induced after LPS injection. In contrast, nuclear Bach1 was significantly but transiently decreased after LPS treatment. Rats were also administered hemin (50 mg/kg body weight) intravenously to elevate heme concentrations, which decreased nuclear Bach1 levels. Our results suggest that elevated hepatic free heme may be associated with a decline of nuclear Bach1, and induction of Bach1 mRNA may compensate for the decreased nuclear Bach1 after LPS treatment in the rat liver. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Interrelationships Between Serum Levels of Procalcitonin and Inflammatory Markers in Patients Who Visited a General Medicine Department 299 306 EN Jo Araki Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosuke Oka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Hanayama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroko Ogawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichi Itoshima Department of Laboratory Medicine, Okayama University Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62221 Various laboratory markers of inflammation are utilized in general practice, but their clinical diagnostic significance is often ambiguous. In the present study, we determined the clinical significance of the examination of serum levels of procalcitonin (PCT) by comparing the PCT levels with the levels of other inflammatory markers, based on a retrospective review of 332 PCT-positive patients, including cases of bacterial infection (20.5%), non-specific inflammation (20.8%), neoplasm (9.9%), connective tissue diseases (8.4%), and non-bacterial infection (7.2%), were analyzed. The serum PCT level was highest in the bacterial infection group (1.94 ng/ml) followed by the non-specific inflammatory group (0.58 ng/ml) and neoplastic diseases group (0.34 ng/ml). The serum PCT level was positively correlated with serum levels of C-reactive protein (rho=0.62), soluble interleukin-2 receptor (sIL-2R; rho=0.69), and ferritin, the plasma level of D-dimer, and white blood cell count, and negatively correlated with the serum albumin level (rho=−0.52), hemoglobin concentration, and platelet count. The serum PCT level showed a stronger positive correlation with the serum sIL-2R level than the other biomarkers. The results suggest that an increased PCT level may indicate not only an infectious state but also a non-bacterial inflammatory condition in the diagnostic process in general practice. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Efficacy and Safety of Early Intravenous Landiolol on Myocardial Salvage in Patients with ST-segment Elevation Myocardial Infarction before Primary Percutaneous Coronary Intervention: A Randomized Study 289 297 EN Masakazu Miyamoto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Osawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Mori Department of Cardiology, Tsuyama Central Hospital Masaki Yoshikawa Department of Cardiology, Fukuyama City Hospital Takefumi Oka Department of Cardiology, Tsuyama Central Hospital Keishi Ichikawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62220 Early treatment with an oral β-blocker is recommended in patients with a ST-segment–elevation myocardial infarction (STEMI). In this multicenter study, we evaluated the effects of a continuous administration of landiolol, an ultrashort-acting β-blocker, before primary percutaneous coronary intervention (PCI) on myocardial salvage and its safety in STEMI patients. A total of 47 Japanese patients with anterior or lateral STEMI undergoing a primary PCI within 12 h of symptom onset were randomized to receive intravenous landiolol (started at 3 μg/min/kg dose and continued to a total of 50 mg; n=23) or not (control; n=24). Patients with Killip class III or more were excluded. The primary outcome was the myocardial salvage index on cardiac magnetic resonance imaging (MRI) performed 5-7 days after the PCI. Cardiac MRI was performed in 35 patients (74%). The myocardial salvage index in the landiolol group was significantly greater than that in the control group (44.4±14.6% vs. 31.7±18.9%, respectively; p=0.04). There were no significant differences in adverse events at 24 h between the landiolol and control groups. A continuous administration of landiolol before a primary PCI may increase the degree of myocardial salvage without additional hemodynamic adverse effects within the first 24 h after STEMI. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1347-6947 85 1 2021 Synthesis of (12R,13S)-pyriculariol and (12R,13S)-dihydropyriculariol revealed that the rice blast fungus, Pyricularia oryzae, produces these phytotoxins as racemates 134 142 EN Yuta Nagashima Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University Ayaka Sasaki Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University Ryoya Hiraoka Graduate School of Environmental and Life Science, Okayama University Yuko Onoda Graduate School of Environmental and Life Science, Okayama University Koji Tanaka Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University Zi-Yi Wang Graduate School of Environmental and Life Science, Okayama University Atsuki Kuwana Graduate School of Environmental and Life Science, Okayama University Yuki Sato Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University Yuji Suzuki Laboratory of Plant Nutrition and Function, Graduate School of Agricultural Science, Tohoku University Minoru Izumi Graduate School of Environmental and Life Science, Okayama University Shigefumi Kuwahara Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University Manabu Nukina Professor Emeritus, Yamagata University Hiromasa Kiyota Graduate School of Environmental and Life Science, Okayama University Synthesis of assumed natural (12R,13S)-enantiomers of pyriculariol (1) and dihydropyriculariol (2), phytotoxins isolated from rice blast disease fungus, Pyricularia oryzae, was achieved using Wittig reaction or microwave-assisted Stille coupling reaction as the key step. The synthesis revealed that the natural 1 and 2 are racemates. Foliar application test on a rice leaf indicated that both the salicylaldehyde core and side chain were necessary for phytotoxic activity. The fungus is found to produce optically active phytotoxins when incubated with rotary shaker, but racemic ones when cultured using an aerated jar fermenter. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 2 2021 Lactoferrin-like Immunoreactivity in Distinct Neuronal Populations in the Mouse Central Nervous System 153 167 EN Shigeyoshi Shimaoka Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical and Pharmaceutical University Hitomi Hamaoka Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical and Pharmaceutical University Junji Inoue Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical and Pharmaceutical University Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikuo Tooyama Molecular Neuroscience Research Center, Shiga University of Medical Science Yoichi Kondo Molecular Neuroscience Research Center, Shiga University of Medical Science Original Article 10.18926/AMO/61894 Lactoferrin (Lf) is an iron-binding glycoprotein mainly found in exocrine secretions and the secondary granules of neutrophils. In the central nervous system (CNS), expression of the Lf protein has been reported in the lesions of some neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, as well as in the aged brain. Lf is primarily considered an iron chelator, protecting cells from potentially toxic iron or iron-requiring microorganisms. Other biological functions of Lf include immunomodulation and transcriptional regulation. However, the roles of Lf in the CNS have yet to be fully clarified. In this study, we raised an antiserum against mouse Lf and investigated the immunohistochemical localization of Lf-like immunoreactivity (Lf-LI) throughout the CNS of adult mice. Lf-LI was found in some neuronal populations throughout the CNS. Intense labeling was found in neurons in the olfactory systems, hypothalamic nuclei, entorhinal cortex, and a variety of brainstem nuclei. This study provides detailed information on the Lf-LI distribution in the CNS, and the findings should promote further understanding of both the physiological and pathological significance of Lf in the CNS. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1618-2642 413 2021 Speciation of chromium in water samples using microfluidic paper-based analytical devices with online oxidation of trivalent chromium 3339 3347 EN Abdellah Muhammed Center for Environmental Science, College of Natural and Computational Sciences, Addis Ababa University Ahmed Hussen Center for Environmental Science, College of Natural and Computational Sciences, Addis Ababa University Takashi Kaneta Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Speciation of chromium (Cr) was demonstrated using microfluidic paper-based analytical devices (μ-PADs) that permit the colorimetric determination of hexavalent chromium (Cr(VI)) and trivalent chromium (Cr(III)) via online oxidation. The μ-PADs consist of left and right channels that allow the simultaneous measurements of Cr(VI) and total Cr based on the colorimetric reaction of Cr(VI) with 1,5-diphenylcarbazide (DPC). For the determination of Cr(VI), a sample solution was directly reacted with DPC in the left channels whereas total Cr was determined in the right channels, which permitted online oxidation in the pretreatment zone containing cerium (IV) (Ce(IV)) followed by a colorimetric reaction with DPC. We found that the online oxidation of Cr(III) proceeded 100% whereas Ce(IV) inhibited the reaction of Cr(VI) with DPC. Therefore, speciation can be achieved by measuring the Cr(VI) and total Cr in the left and right channels followed by the subtraction of Cr(VI) from total Cr. The limits of detection and quantification were 0.008 and 0.02 mg L−1 for Cr(VI) and 0.07 and 0.1 mg L−1 for Cr(III) or total Cr, respectively. The linear dynamic ranges were 0.02–100 mg L−1 and 0.1–60 mg L−1 for Cr(VI) and Cr(III), respectively. The RSDs were less than 7.5%. The results obtained using μ-PADs were in good agreement with those obtained via ICP-OES with recoveries of 92–108% for Cr(III) and 108–110% for Cr (VI) using μ-PADs, and 106–110% for total Cr using ICP-OES. Thus, the μ-PADs could potentially be utilized for the speciation of chromium in developing countries where environmental pollution and the availability of sophisticated instruments are significant problems. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 00219258 296 2021 Covalent N-arylation by the pollutant 1,2-naphthoquinone activates the EGF receptor 100524 EN Kengo Nakahara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kyohei Hamada Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoki Tsuchida Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nobumasa Takasugi Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumi Abiko Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba Kazuhiko Shien Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshito Kumagai Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The epidermal growth factor receptor (EGFR) is the most intensively investigated receptor tyrosine kinase. Several EGFR mutations and modifications have been shown to lead to abnormal self-activation, which plays a critical role in carcinogenesis. Environmental air pollutants, which are associated with cancer and respiratory diseases, can also activate EGFR. Specifically, the environmental electrophile 1,2-naphthoquinone (1,2-NQ), a component of diesel exhaust particles and particulate matter more generally, has previously been shown to impact EGFR signaling. However, the detailed mechanism of 1,2-NQ function is unknown. Here, we demonstrate that 1,2-NQ is a novel chemical activator of EGFR but not other EGFR family proteins. We found that 1,2-NQ forms a covalent bond, in a reaction referred to as N-arylation, with Lys80, which is in the ligand-binding domain. This modification activates the EGFR–Akt signaling pathway, which inhibits serum deprivation–induced cell death in a human lung adenocarcinoma cell line. Our study reveals a novel mode of EGFR pathway activation and suggests a link between abnormal EGFR activation and environmental pollutant–associated diseases such as cancer. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0021-9606 154 9 2021 Formation of hot ice caused by carbon nanobrushes. II. Dependency on the radius of nanotubes 094502 EN Masakazu Matsumoto Research Institute for Interdisciplinary Science, Okayama University Takuma Yagasaki Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University Hideki Tanaka Research Institute for Interdisciplinary Science, Okayama University Stable crystalline structures of confined water can be different from bulk ice. In Paper I [T. Yagasaki et al., J. Chem. Phys. 151, 064702 (2019)] of this study, it was shown, using molecular dynamics (MD) simulations, that a zeolite-like ice structure forms in nanobrushes consisting of (6,6) carbon nanotubes (CNTs) when the CNTs are located in a triangle arrangement. The melting temperature of the zeolite-like ice structure is much higher than the melting temperature of ice Ih when the distance between the surfaces of CNTs is ∼0.94 nm, which is the best spacing for the bilayer structure of water. In this paper, we perform MD simulations of nanobrushes of CNTs that are different from (6,6) CNTs in radius. Several new porous ice structures form spontaneously in the MD simulations. A stable porous ice forms when the radius of its cavities matches the radius of the CNTs well. All cylindrical porous ice structures found in this study can be decomposed into a small number of structural blocks. We provide a new protocol to classify cylindrical porous ice crystals on the basis of this decomposition. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 A Japanese Patient with Gastric Cancer and Dihydropyrimidine Dehydrogenase Deficiency Presenting with DPYD Variants 557 562 EN Mikako Ishiguro Department of Internal Medicine, Tsuyama Chuo Hospital Ryuta Takenaka Department of Internal Medicine, Tsuyama Chuo Hospital Kenichiro Ogura Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences Akira Hiratsuka Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences Hiromasa Takeda Department of Internal Medicine, Tsuyama Chuo Hospital Daisuke Kawai Department of Internal Medicine, Tsuyama Chuo Hospital Hirofumi Tsugeno Department of Internal Medicine, Tsuyama Chuo Hospital Shigeatsu Fujiki Department of Internal Medicine, Tsuyama Chuo Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/61217 A 63-year-old Japanese male with stomach adenocarcinoma received oral 5-fluorouracil derivative, cisplatin and trastuzumab chemotherapy. On day 8, severe diarrhea and mucositis developed; chemotherapy was stopped. On day 14, the patient developed renal dysfunction and febrile neutropenia. He also suffered from pneumonia due to Candida albicans. Systemic symptoms improved after intensive conservative treatment. Best supportive care was continued until the patient died from gastric cancer. The dihydropyrimidine dehydroge-nase protein level was low at 3.18 U/mg protein. The result of DPYD genotyping revealed three variants at posi-tions 1615 (G > A), 1627 (A > G), and 1896 (T > C) in exons 13, 13, and 14, respectively. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 Clinical Application of the Ratio of Serum Bone Isoform to Total Alkaline Phosphatase in General Practice 467 474 EN Yuya Yokota Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akemi Ando Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Hanayama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kou Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroko Ogawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikako Obika Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Ueda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/61205 Alkaline phosphatase (ALP) is an enzyme that is expressed in a variety of tissues. Among the isoforms of ALP, bone-specific alkaline phosphatase (BAP) is used as a marker for evaluating bone metabolism. We investigated the clinical usefulness of the ratio of serum BAP to total ALP for the diagnosis of various disorders in general practice. We retrospectively analyzed the cases of 107 Japanese patients whose serum BAP levels were exam-ined, focusing on clinical characteristics. We observed that the BAP/ALP ratios of the patients with fever and those with inflammatory diseases were significantly lower than the ratios of other patient groups. The BAP/ALP ratios of the patients with osteoporosis and those with metabolic bone diseases were higher than those of the patients with other conditions. The BAP/ALP ratio was found to be negatively correlated with age, a cor-relation that has not been found in other ethnicities. The serum BAP/ALP ratio was inversely correlated with serum CRP levels but was positively correlated with serum albumin levels and hemoglobin concentrations. Collectively, our results suggest that the BAP/ALP ratio could be a useful predictor for important geriatric con-ditions seen in general practice. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 Clinical Relevance of Serum Prolactin Levels to Inflammatory Reaction in Male Patients 381 389 EN Koichiro Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Hanayama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kou Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Miyoshi Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroko Ogawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikako Obika Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichi Itoshima Department of Laboratory Medicine, Okayama University Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/60797 To clarify the relevance of prolactin (PRL) to clinical parameters in patients who visited our general medicine department, medical records of 353 patients in whom serum PRL levels were measured during the period from 2016 to 2018 were retrospectively reviewed. Data for 140 patients (M/F: 42/98) were analyzed after excluding patients lacking detailed records and patients taking dopaminergic agents. Median serum PRL levels were significantly lower in males than females: 6.5 ng/ml (IQR: 4.2-10.3) versus 8.1 ng/ml (5.9-12.9), respectively. Pain and general fatigue were the major symptoms at the first visit, and past histories of hypertension and dyslipidemia were frequent. Male patients with relatively high PRL levels (≥ 10 ng/ml) had significantly lower levels of serum albumin and significantly higher levels of serum LDH than those with low PRL (< 10 ng/ml). There were significant correlations of male PRL level with the erythrocyte sedimentation rate (R=0.62), serum LDH level (R=0.39) and serum albumin level (R=−0.52), while the level of serum CRP (R=0.33) showed an insignificant but weak positive correlation with PRL level. Collectively, these results show that PRL levels had gender-specific relevance to various clinical factors, with PRL levels in males being significantly related to inflammatory status. No potential conflict of interest relevant to this article was reported.

American Institute of Physics Acta Medica Okayama 0021-9606 153 11 2020 Structure and phase behavior of high-density ice from molecular-dynamics simulations with the ReaxFF potential 114501 EN Yuji Adachi Graduate School of Natural Sciences, Okayama University Kenichiro Koga 2Department of Chemistry, Okayama University We report a molecular dynamics simulation study of dense ice modeled by the reactive force field (ReaxFF) potential, focusing on the possibility of phase changes between crystalline and plastic phases as observed in earlier simulation studies with rigid water models. It is demonstrated that the present model system exhibits phase transitions, or crossovers, among ice VII and two plastic ices with face-centered cubic (fcc) and body-centered cubic (bcc) lattice structures. The phase diagram derived from the ReaxFF potential is different from those of the rigid water models in that the bcc plastic phase lies on the high-pressure side of ice VII and does the fcc plastic phase on the low-pressure side of ice VII. The phase boundary between the fcc and bcc plastic phases on the pressure, temperature plane extends to the high-temperature region from the triple point of ice VII, fcc plastic, and bcc plastic phases. Proton hopping, i.e., delocalization of a proton, along between two neighboring oxygen atoms in dense ice is observed for the ReaxFF potential but only at pressures and temperatures both much higher than those at which ice VII–plastic ice transitions are observed. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Successful Vancomycin Dose Adjustment in a Sepsis patient with Bacterial Meningitis Using Cystatin C 365 370 EN Masayuki Chuma Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Masateru Kondo Department of Pharmacy, Tokushima University Hospital Yoshito Zamami Department of Pharmacy, Tokushima University Hospital Kenshi Takechi Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Mitsuhiro Goda Department of Pharmacy, Tokushima University Hospital Naoto Okada Department of Pharmacy, Tokushima University Hospital Akitomo Shibata Department of Pharmacy, Saiseikai Kumamoto Hospital Mizuho Asada Department of Pharmacy, Medical Hospital, Tokyo Medical and Dental University Jun Oto Department of Emergency and Critical Care Medicine, Tokushima University Graduate School of Biomedical Sciences Hiroaki Yanagawa Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Keisuke Ishizawa Department of Pharmacy, Tokushima University Hospital Case Report 10.18926/AMO/60376 Cystatin C-guided vancomycin (VCM) dosing is useful in critically ill patients. Its usefulness in septic patients with bacterial meningitis remains unknown, as there are no published reports. In this study, we sought to clarify its benefit. Cystatin C was used to guide VCM dosing in a septic bacterial meningitis patient with normal kidney function, according to therapeutic drug monitoring (TDM). Using cystatin C, the Bayesian method-based TDM made optimal VCM dosing possible, and decreased the predicted error (4.85 mg/L) compared to serum creatinine (16.83 mg/L). We concluded TDM of VCM using cystatin C can be considered in sepsis patients with bacterial meningitis with normal kidney function. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1022-1352 220 9 2019 Rapid Synthesis of Poly(methyl methacrylate) Particles with High Molecular Weight by Soap‐Free Emulsion Polymerization Using Water‐in‐Oil Slug Flow 1900021 EN Takaichi Watanabe Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Kengo Karita Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Koki Tawara Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Takuya Soga Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Tsutomu Ono Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University flow process for the production of poly(methyl methacrylate) (PMMA) particles is proposed by soap‐free emulsion polymerization using a water‐in‐oil (W/O) slug flow in a microreactor. Thin oil films generated around the dispersed aqueous phase of the W/O slug prevent the prepared particles from adhesion to the microchannel wall, enabling the continuous production of PMMA particles without clogging. The effects of the linear flow rate of the slug flow and the addition of ethanol in the dispersed aqueous phase on the polymerization are evaluated. It is found that increasing the linear flow rate of the slug flow or the addition of ethanol in the dispersed aqueous phase results in PMMA particles with high molecular weight (≈1500 kg mol−1) in 20 min reaction time. It is believed that this process would be a promising way to prepare polymer particles with high molecular weight in a short reaction time. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0947-6539 25 66 2019 Mechanistic Insights into Rhenium-Catalyzed Regioselective C-Alkenylation of Phenols with Internal Alkynes 15189 15197 EN Masahito Murai Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Masaki Yamamoto Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Kazuhiko Takai Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University A (μ-aryloxo)rhenium complex was isolated and confirmed as a key precatalyst for rhenium-catalyzed ortho-alkenylation (C-alkenylation) of unprotected phenols with alkynes. The reaction exclusively provided ortho-alkenylphenols; the formation of para or multiply alkenylated phenols and hydrophenoxylation (O-alkenylation) products was not observed. Several mechanistic experiments excluded a classical Friedel-Crafts-type mechanism, leading to the proposed phenolic hydroxyl group assisted electrophilic alkenylation as the most plausible reaction mechanism. For this purpose, the use of rhenium, a metal between the early and late transition metals in the periodic table, was key for the activation of both the soft carbon-carbon triple bond of the alkyne and the hard oxygen atom of the phenol, at the same time. ortho-Selective alkenylation with allenes also provided the corresponding adducts with a substitution pattern different from that obtained by the addition reaction with alkynes. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 0022-3263 85 2 2019 Formal Total Synthesis of Manzacidin B via Sequential Diastereodivergent Henry Reaction 798 805 EN Yuya Araki Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Natsumi Miyoshi Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Kazuki Morimoto Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Takayuki Kudoh Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Haruki Mizoguchi Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Akira Sakakura Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University A formal total synthesis of manzacidin B is described. beta,beta-Disubstituted gamma-hydroxy-beta-aminoalcohol, the key structure of manzacidin B, is stereoselectively constructed via sequential Henry reactions. By taking advantage of noncovalent interactions, such as intramolecular hydrogen bonding and chelation, we could diastereodivergently control the stereoselectivity of the Henry reaction. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 1 2020 A Promising New Anti-Cancer Strategy: Iron Chelators Targeting CSCs 1 6 EN Yuehua Chen Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Boyi Xing Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jiping Qi Department of Pathology, the First Affiliated Hospital of Harbin Medical University Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Matsukawa Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/57946 Iron is a trace but vital element in the human body and is necessary for a multitude of crucial processes in life. However, iron overload is known to induce carcinogenesis via oxidative stress. Cancer cells require large amounts of iron for their rapid division and cell growth. Iron was recently found to play a role in cancer stem cells (CSCs); it maintains stemness during development. Iron also plays an important role in stemness by moderating reactive oxygen species. Thus, iron metabolism in CSCs is a promising therapeutic target. In this review, we summarize the roles of iron in cancer cells and CSCs. We also summarize anti-cancer therapeutic studies with iron chelators and describe our expectation of a new therapeutic strategy for CSCs on the basis of our findings. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 0022-3263 84 23 2019 Copper-Catalyzed Regioselective Aminothiolation of Aromatic and Aliphatic Alkenes with N-Fluorobenzenesulfonimide and Thiols through Three-Component Radical Coupling 15373 15379 EN Masayuki Iwasaki Research Institute for Interdisciplinary Science, Okayama University Kosei Nonaka Graduate School of Natural Science and Technology, Okayama University Song Zou Yuta Sawanaka Graduate School of Natural Science and Technology, Okayama University Takaaki Shinozaki Graduate School of Natural Science and Technology, Okayama University Tomoya Fujii Graduate School of Natural Science and Technology, Okayama University Kiyohiko Nakajima Graduate School of Natural Science and Technology, Okayama University Yasushi Nishihara Research Institute for Interdisciplinary Science, Okayama University Copper-catalyzed regioselective aminothiolation of terminal and internal alkenes with N-fluorobenzenesulfonimide and thiols has been developed. The three-component reaction is promoted by the addition of dimethyl sulfide. In addition to aromatic alkenes, aliphatic alkenes are subjected to the reaction, affording various aminothiolation adducts as single regioisomers. The radical process is proposed by preliminary mechanistic studies, involving radical trap and radical clock experiments. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 00222623 62 19 2019 Competitive Binding Assay with an Umbelliferone-Based Fluorescent Rexinoid for Retinoid X Receptor Ligand Screening 8809 8818 EN Shoya Yamada Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayu Kawasaki Michiko Fujihara Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaki Watanabe Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Takamura Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Maho Takioku Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromi Nishioka Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Takeuchi Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makoto Makishima Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine Tomoharu Motoyama Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka Sohei Ito Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka Hiroaki Tokiwa Department of Chemistry and Research Center of Smart Molecules, Rikkyo University Shogo Nakano Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka Hiroki Kakuta Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ligands for retinoid X receptors (RXRs), "rexinoids", are attracting interest as candidates for therapy of type 2 diabetes and Alzheimer's and Parkinson's diseases. However, current screening methods for rexinoids are slow and require special apparatus or facilities. Here, we created 7-hydroxy-2-oxo-6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2H-chromene-3-carboxylic acid (10, CU-6PMN) as a new fluorescent RXR agonist and developed a screening system of rexinoids using 10. Compound 10 was designed based on the fact that umbelliferone emits strong fluorescence in a hydrophilic environment, but the fluorescence intensity decreases in hydrophobic environments such as the interior of proteins. The developed assay using 10 enabled screening of rexinoids to be performed easily within a few hours by monitoring changes of fluorescence intensity with widely available fluorescence microplate readers, without the need for processes such as filtration. No potential conflict of interest relevant to this article was reported.

American Institute of Physics Acta Medica Okayama 00219606 144 22 2016 A reference-modified density functional theory: An application to solvation free-energy calculations for a Lennard-Jones solution 224104 EN Tomonari Sumi Department of Chemistry, Faculty of Science, Okayama University Yutaka Maruyama Co-Design Team, Exascale Computing Project, RIKEN Advanced Institute for Computational Science Ayori Mitsutake Co-Design Team, Exascale Computing Project, RIKEN Advanced Institute for Computational Science Kenichiro Koga Department of Chemistry, Faculty of Science, Okayama University In the conventional classical density functional theory (DFT) for simple fluids, an ideal gas is usually chosen as the reference system because there is a one-to-one correspondence between the external field and the density distribution function, and the exact intrinsic free-energy functional is available for the ideal gas. In this case, the second-order density functional Taylor series expansion of the excess intrinsic free-energy functional provides the hypernetted-chain (HNC) approximation. Recently, it has been shown that the HNC approximation significantly overestimates the solvation free energy (SFE) for an infinitely dilute Lennard-Jones (LJ) solution, especially when the solute particles are several times larger than the solvent particles [T. Miyata and J. Thapa, Chem. Phys. Lett. 604, 122 (2014)]. In the present study, we propose a reference-modified density functional theory as a systematic approach to improve the SFE functional as well as the pair distribution functions. The second-order density functional Taylor series expansion for the excess part of the intrinsic free-energy functional in which a hard-sphere fluid is introduced as the reference system instead of an ideal gas is applied to the LJ pure and infinitely dilute solution systems and is proved to remarkably improve the drawbacks of the HNC approximation. Furthermore, the third-order density functional expansion approximation in which a factorization approximation is applied to the triplet direct correlation function is examined for the LJ systems. We also show that the third-order contribution can yield further refinements for both the pair distribution function and the excess chemical potential for the pure LJ liquids. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry Acta Medica Okayama 14639076 16 46 2014 Model-potential-free analysis of small angle scattering of proteins in solution: insights into solvent effects on protein-protein interaction 25492 25497 EN Tomonari Sumi Department of Chemistry, Faculty of Science, Okayama University Hiroshi Imamura Graduate School of Advanced Integration Science, Chiba University Takeshi Morita Graduate School of Advanced Integration Science, Chiba University Yasuhiro Isogai Department of Biotechnology, Toyama Prefectural University Keiko Nishikawa Graduate School of Advanced Integration Science, Chiba University To extract protein-protein interaction from experimental small-angle scattering of proteins in solutions using liquid state theory, a model potential consisting of a hard-sphere repulsive potential and the excess interaction potential has been introduced. In the present study, we propose a model-potential-free integral equation method that extracts the excess interaction potential by using the experimental small-angle scattering data without specific model potential such as the Derjaguin-Landau-Verwey-Overbeek (DLVO)-type model. Our analysis of experimental small-angle X-ray scattering data for lysozyme solution shows both the stabilization of contact configurations of protein molecules and a large activation barrier against the formation of the contact configurations in addition to the screened Coulomb repulsion. These characteristic features, which are not well-described by the DLVO-type model, are interpreted as solvent effects. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 01928651 36 26 2015 Erratum: "A solvation-free-energy functional: A reference-modified density functional formulation" [J. Comput. Chem. 2015, 36, 1359-1369]. 2009 2011 EN Tomonari Sumi Department of Chemistry, Faculty of Science, Okayama University Ayori Mitsutake Department of Physics, Keio University Yutaka Maruyama Department of Physics, Keio University No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 5 2019 The Role of High Mobility Group Box-1 in Epileptogenesis 383 386 EN Li Fu Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Nishibori Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/57367 High mobility group box-1 (HMGB1) is a non-histone, DNA-binding nuclear protein belonging to the family of damage-associated molecular patterns (DAMPs). HMGB1 has been reported to play an important role during epileptogenesis although the mechanisms of its actions are still not clear. Many hypotheses have been suggested especially about the relationship between HMGB1 and inflammation responses and blood-brain barrier disruption during epileptogenesis. In this review, we will mainly discuss the role of HMGB1 in epileptogenesis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 5 2019 Histidine-rich Glycoprotein Modulates the Blood-vascular System in Septic Condition 379 382 EN Hidenori Wake Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Review 10.18926/AMO/57366 Histidine-rich glycoprotein (HRG) is a 75 kDa glycoprotein synthesized in the liver whose plasma concentration is 100-150 μg/ml. HRG has been shown to modulate sepsis-related biological reactions by binding to several substances and cells, including heparin, factor XII, fibrinogen, thrombospondin, plasminogen, C1q, IgG, heme, LPS, dead cells, bacteria, and fungi. Therefore, reduction of plasma HRG levels in sepsis leads to dysregulation of coagulation, fibrinolysis, and immune response, resulting in disseminated intravascular coagulation and multiple organ failure. This review summarizes the binding and functional properties of HRG in sepsis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 4 2019 Construction and Characterization of a PGN_0297 Mutant of Porphyromonas gingivalis: Evidence of the Contribution of PGN_0297 to Gingipain Activity 315 323 EN Shintaro Ono Department of Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaaki Nakayama Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Tachibana Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Abu Saleh Muhammad Shahriar Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Wang Heling Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shogo Takashiba Department of Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoya Ohara Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/56933 The periodontal pathogen Porphyromonas gingivalis shows colonial pigmentation on blood agar and produces gingipains (Kgp, RgpA, and RgpB), cysteine proteases involved in an organism’s virulence and pigmentation. We showed previously that deletion of the PGN_0300 gene abolished the pigmentation activity and reduced the proteolytic activity of gingipains. The role of the PGN_0297 gene, which consists of an operon with the PGN_0300 gene, is unclear. Herein we examined the effect of PGN_0297 gene deletion on the pigmentation and proteolytic activities and transcriptional levels of gingipains. A PGN_0297 gene deletion mutant (ΔPGN_0297) did not exhibit the pigmentation. The proteolytic activity of the gingipains was decreased in the culture supernatant and on the cell surface of ΔPGN_0297. The mutant ΔPGN_0297 failed to attenuate Akt phosphorylation at Thr308 and Ser473, but both phosphorylations were attenuated in the wild-type and its complementation strain. The deletion of PGN_0297 gene did not substantially affect the transcriptional levels of the gingipain genes kgp, rgpA, and rgpB. Taken together, these results indicate that PGN_0297 is closely involved in the secretion and maturation of gingipains. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 4 2019 Dynamic Reorganization of Microtubule and Glioma Invasion 285 297 EN Yoshihiro Otani Department of Neurosurgery, The University of Texas Health Science Center at Houston Tomotsugu Ichikawa Department of Neurosurgery, Kagawa Prefectural Central Hospital Kazuhiko Kurozumi Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/56930 Gliomas are characterized as highly diffuse infiltrating tumors, and currently available treatments such as surgery, radiation and chemotherapy are unfeasible or show limited efficacy against these tumors. Recent genetic and epigenetic analyses of glioma have revealed increasing evidence of the role of driver genetic alterations in glioma development and led to the identification of prognostic factors. Despite these findings, the survival rates of glioma patients remain low, and alternative treatments and novel targets are needed. Recent studies identified neural stem cells as the possible origin of gliomas, and some evidence has revealed shared functions and mechanisms between glioma cells and neurons, also supporting their similarity. The cytoskeleton plays important roles in the migration of normal cells as well as cancer cells. Recent reports have described a role for microtubules, a component of the cytoskeleton, in glioma invasion. Notably, several factors that regulate microtubule functions, such as microtubule-associated proteins, plus-end tracking proteins, or motor proteins, are upregulated in glioma tissues compared with normal tissue, and upregulation of these factors is associated with high invasiveness of glioma cells. In this review, we describe the mechanism of microtubules in glioma invasion and discuss the possibility of microtubule-targeted therapy to inhibit glioma invasion. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 3 2019 Improvement of Open Bite and Stomatognathic Function in an Axenfeld- Rieger Syndrome Patient by Orthodontic Sectional Arch Mechanics: Clinical Considerations and the Risk of Orthodontic Tooth Movement 255 262 EN Daisuke Seki Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry Nobuo Takeshita Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry Masahiro Seiryu Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry Toru Deguchi Division of Orthodontics, The Ohio State University College of Dentistry Teruko Takano-Yamamoto Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Case Report 10.18926/AMO/56869 Orthodontists need to understand the orthodontic risks associated with systemic disorders. Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant disorder with genetic and morphological variability. The risks of orthodontic treatment in ARS patients have been unclear. Here we describe the correction of an anterior open bite in a 15-year-old Japanese female ARS patient by molar intrusion using sectional archwires with miniscrew implants. An undesirable development of external apical root resorption (EARR) was observed in all intrusive force-applied posterior teeth during the patient’s orthodontic treatment, suggesting that ARS patients have a higher risk of EARR than the general population. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 3 2019 Spiral Trajectory Modulation of Rheotaxic Motile Human Sperm in Cylindrical Microfluidic Channels of Different Inner Diameters 213 221 EN Saori Nishina Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Matsuura Department of Biomedical Engineering, Faculty of Engineering, Okayama University of Science Keiji Naruse Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/56863 We investigated the relationship between human sperm rheotaxis and motile sperm trajectories by using poly-(dimethylsiloxane) (PDMS)-based cylindrical microfluidic channels with inner diameters of 100 μm, 50 μm, and 70 μm, which corresponded to the inner diameter of the human isthmus, the length of a sperm and a diameter intermediate between the two, respectively. We counted the number of rheotaxic sperm and sperm with spiral motion. We also analyzed motile sperm trajectories. As the cylindrical channel diameter was decreased, the percentage of sperm cells exhibiting rheotaxis, the percentage of sperm cells exhibiting spiral motion, the frequency-to-diameter ratio of the sperm cells’ spiral trajectories, and the surface area of the microfluidic channel increased, while the flagellar motion at the channel wall decreased. The percentage of sperm exhibiting a spiral trajectory and the frequency-to-diameter ratio of the sperm cells’ spiral trajectories were thus affected by the channel diameter. Our findings suggest that the oviduct structure affects the swimming properties of sperm cells, guiding them from the uterus to the ampulla for egg fertilization. These results could contribute to the development of motile sperm-sorting microfluidic devices for assisted reproductive technologies. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 2 2019 Collagen XVIII Deposition in the Basement Membrane Zone beneath the Newly Forming Epidermis during Wound Healing in Mice 135 146 EN Takahiro Maeba Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Tomoko Yonezawa Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Mitsuaki Ono Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Yasuko Tomono Shigei Medical Research Institute Ritva Heljasvaara Center for Cancer Biomarkers CCBIO, Department of Biomedicine, University of Bergen Taina Pihlajaniemi Oulu Center for Cell-Matrix Research, Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu Kiichi Inagawa Department of Plastic and Reconstructive Surgery, Kawasaki Medical School, Kurashiki Toshitaka Oohashi Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Original Article 10.18926/AMO/56649 The basement membrane (BM) is composed of various extracellular molecules and regulates tissue regeneration and maintenance. Here, we demonstrate that collagen XVIII was spatiotemporally expressed in the BM during skin wound healing in a mouse excisional wound-splinting model. Re-epithelialization was detected at days 3 and 6 post-wounding. The ultrastructure of epidermal BM was discontinuous at day 3, whereas on day 6 a continuous BM was observed in the region proximal to the wound edge. Immunohistochemistry demonstrated that collagen XVIII was deposited in the BM zone beneath newly forming epidermis in day 3 and 6 wounds. Laminin-332, known to be the earliest BM component appearing in wounds, was colocalized with collagen XVIII in the epidermal BM zone at days 3 and 6. The deposition of α1(IV) collagen and nidogen-1 in the epidermal BM zone occurred later than that of collagen XVIII. We also observed the short isoform of collagen XVIII in the epidermal BM zone at day 3 post-wounding. Collectively, our results suggested that collagen XVIII plays a role in the formation of the dermal-epidermal junction during re-epithelialization, and that it is the short isoform that is involved in the early phase of re-epithelialization. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 1 2019 The Role of Kallikrein-Related Peptidases in Atopic Dermatitis 1 6 EN Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/56452 Excessive protease activity is a characteristic abnormality that affects the epidermal barrier in patients with atopic dermatitis (AD). Kallikrein-related peptidases (KLKs) are excessively expressed in AD lesions, and it is suggested that the abnormal action of KLKs is involved in the skin barrier dysfunction in AD. In other words, overexpressed KLKs disrupt the normal barrier function, and due to that breakdown, external substances that can become antigens of AD easily invade the epidermis, resulting in dermatitis, coupled with the induction of Th2 cytokines. Further investigations are required to elucidate the role of KLKs in AD; this knowledge could contribute to the design of new therapeutic and prophylactic drugs for AD. No potential conflict of interest relevant to this article was reported.

WILEY‐VCH Acta Medica Okayama 0947-6539 22 6 2016 Stereodivergent Synthesis and Stereochemical Reassignment of the C79-C104 Fragment of Symbiodinolide 1984 1996 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takayuki Fujiwara Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Yohei Kawakubo Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Daisuke Uemura Department of Chemistry, Faculty of Science, Kanagawa University We have synthesized eight possible diastereoisomers 3 a-h of the C79-C97 fragment of symbiodinolide (1) in a stereodivergent manner by utilizing a dithiane addition to the aldehyde as a key step. Comparison of the 13 C NMR chemical shifts of the natural product 1 and the synthetic products 3 a-h indicated that the relative stereostructure of this fragment in symbiodinolide (1) is that represented in 3 a or f. We have stereodivergently synthesized eight possible diastereoisomers of the C94-C104 fragment 4 a-h, and we have compared their 13 C NMR chemical shifts with those of the natural product, which established the relative stereochemistry of this fragment to be that described in diastereoisomers 4 a or e. By combining the stereostructural outcomes of the C79-C97 and C94-C104 fragments, we have proposed four candidate compounds of the C79-C104 fragment 2 a-d. We also synthesized diastereoisomers 2 a and b (2 a in the preceding article; Chem. Eur. J. 2015, DOI: 10.1002/chem.201503880) by a Julia-Kocienski olefination and diastereoisomers 2 c and d by a Wittig reaction. By comparing the 13 C NMR chemical shifts of natural symbiodinolide (1) with those of the synthetic products 2 a-d, we have reassigned the stereostructure of the C79-C104 fragment of natural product 1 to be that depicted in diastereoisomer 2 b. No potential conflict of interest relevant to this article was reported.

Wiley-VCH Acta Medica Okayama 0947-6539 22 6 2016 Stereoselective Synthesis of the Proposed C79-C104 Fragment of Symbiodinolide 1979 1983 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takayuki Fujiwara Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Yohei Kawakubo Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Daisuke Uemura Department of Chemistry, Faculty of Science, Kanagawa University Stereoselective and streamlined synthesis of the proposed C79-C104 fragment 2 of symbiodinolide (1), a polyol marine natural product with a molecular weight of 2860, was achieved. In the synthetic route, the proposed C79-C104 fragment 2 was synthesized by utilizing a Julia-Kocienski olefination and subsequent Sharpless asymmetric dihydroxylation as key transformations in a convergent manner. Detailed comparison of the 13 C NMR chemical shifts between the natural product and the synthetic C79-C104 fragment 2 revealed that the stereostructure at the C91-C99 carbon chain moiety of symbiodinolide (1) should be reinvestigated. No potential conflict of interest relevant to this article was reported.

Wiley‐VCH Acta Medica Okayama 09476539 23 68 2017 Total Synthesis of Two Possible Diastereomers of Natural 6-Chlorotetrahydrofuran Acetogenin and Its Stereostructural Elucidation 17191 17194 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Tomoya Katsube Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Kazuki Okamoto Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University The first total synthesis of two possible diastereomers of natural 6-chlorotetrahydrofuran acetogenin 1 has been achieved. The synthetic route features 5-exo-tet cyclization, Z selective Wittig reaction and Julia olefination for the construction of conjugated diene and enyne moieties, and stereoselective chlorination. Comparison of their 1 H and 13 C NMR data and specific rotation with those of the natural product elucidated the absolute configuration of natural (-)-6-chlorotetrahydrofuran acetogenin 1. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 1523-7060 18 9 2016 Lewis Acid and Fluoroalcohol Mediated Nucleophilic Addition to the C2 Position of Indoles 2020 2023 EN Naoki Morimoto Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Div Pharmaceut Sci Kumika Morioku Okayama Univ, Fac Engn, Dept Appl Chem & Biotechnol Hideyuki Suzuki Okayama Univ, Res Core Interdisciplinary Sci Yasuo Takeuchi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Div Pharmaceut Sci Yuta Nishina Okayama Univ, Res Core Interdisciplinary Sci Indole readily undergoes nucleophilic substitution at the C3 site, and many indole derivatives have been functionalized using this property. Indole also forms indolium, which allows electrophilic addition in acidic conditions, but current examples have been limited to intramolecular reactions. C2 site-selective nucleophilic addition to indole derivatives using fluoroalcohol and a Lewis acid was developed. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 129 2 2017 平成28年度岡山医学会賞　総合研究奨励賞（結城賞） 81 83 EN Masakiyo Sakaguchi Department of Cell Biolgy, Okayama University Graduate School of Medicine, Dentistry 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 平成28年度岡山医学会賞　胸部・循環研究奨励賞（砂田賞） 77 79 EN Yukihiro Saito Department of Cardiovascular Medicine, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 2 2016 アディポカイン「バスピン」の同定とメタボリックシンドロームにおける意義 103 109 EN Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 3 2015 薬剤耐性マラリアに有望な新規抗マラリア薬開発の現況 231 235 EN Hye-Sook Kim Akane Katamoto Akira Sato Yusuke Wataya Hiroyuki Doi No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 3 2015 血管内皮機能を対象にした基礎および臨床医学研究 187 195 EN Hirokazu Tsukahara No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 2 2015 慢性移植片対宿主病に対するタミバロテン（AM80G）の医師主導臨床第Ⅱ相試験 133 137 EN Hisakazu Nishimori Yoshinobu Maeda No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 2 2015 基底膜ツールキットとしてのXV/XVⅢ型コラーゲン遺伝子の機能 103 109 EN Toshitaka Oohashi No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 2 2015 平成26年度岡山医学会賞 総合研究奨励賞（結城賞） 87 90 EN Nanako Ookubo No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 1 2015 REIC/Dkk-3遺伝子発現アデノウイルスベクターを用いた悪性胸膜中皮腫に対する遺伝子治療 47 50 EN Shinichi Toyooka No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 126 3 2014 アストロサイトによる神経機能修飾とパーキンソン病での神経保護 203 208 EN Masato Asanuma No potential conflict of interest relevant to this article was reported.

International Society of Pteridinology Acta Medica Okayama 0933-4807 24 1 2013 First Synthesis of Asperopterin A, an Isoxanthopterin Glycoside from Aspergillus Oryzae 3 6 EN Tadashi Hanaya Hiroshi Yamamoto The key precursor, N-2-(N,N -dimethylaminomethylene)-6-hydroxymethyl-8-methyl-3-[2-(4-nitrophenyl)ethyl]-7-xanthopterin (16) was efficiently prepared from 2,5-diamino-6-methylamino-3H-pyrimidin-4-one (5) and ethyl 3-(tert-butyldimethylsilyloxy)-2-oxopropionate (12), followed by the protection of the pteridine ring. Glycosylation of 16 with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (18) in the presence of tin(IV) chloride yielded the corresponding beta-D-ribofuranoside. Successive removal of the protecting groups of the resulting D-ribofuranoside provided asperopterin A (4b). No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0018-0661 150 1 2013 Acetyl-L-carnitine suppresses thyroid hormone-induced and spontaneous anuran tadpole tail shortening 1 9 EN Hideki Hanada Hirotsugu Kobuchi Masanao Yamamoto Keiko Kashiwagi Kenjiro Katsu Toshihiko Utsumi Akihiko Kashiwagi Junzo Sasaki Masayasu Inoue Kozo Utsumi Mitochondrial membrane permeability transition (MPT) plays a crucial role in apoptotic tail shortening during anuran metamor phosis. L-carnitine is known to shuttle free fatty acids (FFAs) from the cytosol into mitochondria matrix for -oxidation and energy production, and in a previous study we found that treatment with L-carnitine suppresses 3, 3', 5-triiodothyronine (T3) and FFA-induced MPT by reducing the level of FFAs. In the present study we focus on acetyl-L-carnitine, which is also involved in fatty acid oxidation, to determine its effect on T3-induced tail regression in Rana rugosa tadpoles and spontaneous tail regression in Xenopus laevis tadpoles. The ladder-like DNA profile and increases in caspase-3 and caspase-9 indicative of apoptosis in the tails of T3-treated tadpoles were found to be suppressed by the addition of acetyl-L-carnitine. Likewise, acetyl-L-carnitine was found to inhibit thyroid hormone regulated spontaneous metamorphosis in X. laevis tadpoles, accompanied by decreases in caspase and phospholipase A2 activity, as well as non-ladder-like DNA profiles. These findings support our previous conclusion that elevated levels of FFAs initiate MPT and activate the signaling pathway controlling apoptotic cell death in tadpole tails during anuran metamorphosis. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 126 2 2014 平成25年度岡山医学会賞 胸部・循環研究奨励賞（砂田賞） 95 98 EN Atsuko Nakatsuka No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 126 2 2014 平成25年度岡山医学会賞 がん研究奨励賞（林原賞・山田賞） 89 92 EN Joe Hasei No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 00399140 122 2014 Speciation of arsenic in a thermoacidophilic iron-oxidizing archaeon, Acidianus brierleyi, and its culture medium by inductively coupled plasma–optical emission spectroscopy combined with flow injection pretreatment using an anion-exchange mini-column 240 245 EN Naoki Higashidani Takashi Kaneta Nobuyuki Takeyasu Shoji Motomizu Naoko Okibe Keiko Sasaki The thermoacidophilic iron-oxidizing archaeon Acidianus brierleyi is a microorganism that could be useful in the removal of inorganic As from wastewater, because it simultaneously oxidizes As(III) and Fe(II) to As(V) and Fe(III) in an acidic culture medium, resulting in the immobilization of As(V) as FeAsO4. To investigate the oxidation mechanism, speciation of the As species in both the cells and its culture media is an important issue. Here we describe the successive determination of As(III), As(V), and total As in A. brierleyi and its culture medium via a facile method based on inductively coupled plasma–optical emission spectroscopy (ICP–OES) with a flow injection pretreatment system using a mini-column packed with an anion-exchange resin. The flow-injection pretreatment system consisted of a syringe pump, a selection valve, and a switching valve, which were controlled by a personal computer. Sample solutions with the pH adjusted to 5 were flowed into the mini-column to retain the anionic As(V), whereas As(III) was introduced into ICP–OES with no adsorption on the mini-column due to its electrically neutral form. An acidic solution (1 M HNO3) was then flowed into the mini-column to elute As(V) followed by ICP–OES measurement. The same sample was also subjected to ICP–OES without being passed through the mini-column in order to determine the total amounts of As(III) and As(V). The method was verified by comparing the results of the total As with the sum of As(III) and As(V). The calibration curves showed good linearity with limits of detection of 158, 86, and 211 ppb for As(III), As(V), and total As, respectively. The method was successfully applicable to the determination of the As species contained in the pellets of A. brierleyi and their culture media. The results suggested that the oxidation of As(III) was influenced by the presence of Fe(II) in the culture medium, i.e., Fe(II) enhanced the oxidation of As(III) in A. brierleyi. In addition, we found that no soluble As species was contained in the cell pellets and more than 60% of the As(III) in the culture medium was oxidized by A. brierleyi after a 6-day incubation. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 125 3 2013 組織形成因子Fgf10 229 234 EN Hideyo Ohuchi No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 125 3 2013 Th２サイトカインはアトピー性皮膚炎患者における カリクレイン７の発現と機能を増強する 217 220 EN Shin Morizane Kenshi Yamasaki Ai Kajita Kazuko Ikeda Maosheng Zhan Yumi Aoyama Richard L Gallo Keiji Iwatsuki No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 125 3 2013 腫瘍融解アデノウイルスによるE2F1-マイクロRNA-7-EGFR経路を介したオートファジー細胞死の誘導分子機構 195 199 EN Hiroshi Tazawa Syuya Yano Ryosuke Yoshida Yasumoto Yamasaki Tsuyoshi Sasaki Yuuri Hashimoto Shinji Kuroda Masaaki Ouchi Teppei Onishi Futoshi Uno Syunsuke Kagawa Yasuo Urata Toshiyoshi Fujiwara No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0385-5414 73 1 2007 Improved syntheses of D-ribo- and 2-deoxy-D-ribofuranose phospho sugars from methyl β-D-ribopyranoside 581 591 EN Tadashi Hanaya Yuko Koga Heizan Kawamoto Hiroshi Yamamoto Methyl 4-deoxy-4-dimethoxyphosphinoyl-2,3-O-isopropylidene-beta-D-ribopyranoside (12a) and methyl 2,4-dideoxy-4-dimethoxyphosphinoyl-beta-D-erythro-pentopyranoside (20) were efficiently prepared respectively from methyl 2,3-O-isopropylidene-beta-D-ribopyranoside (7a) and its 3,4-O-isopropylidene isomer (7b) in appreciably improved total yields compared with those via previously reported routes. Compounds (12a, 20) were led to D-ribofuranose and 2-deoxy-D-ribofuranose phospho sugars (4, 5). No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0385-5414 72 1 2007 A New Route for Preparation of 2-Deoxy-D-ribofuranose Phospho Sugar 411 420 EN Tadashi Hanaya Hiroyuki Tsukui Naomi Igi Ayashi Noguchi Heizan Kawamoto Hiroshi Yamamoto The addition reaction of dimethyl phosphonate to (2R,4S)-4-(tertbutyldimethylsilyl)oxymethyl-2-methyl-1,3-dioxan-5-one (11a), followed by dehydroxylation, provided 1-O-(tert-butyldimethylsilyl)-3-deoxy-3-dimethoxyphosphinoyl-2,4-O-ethylidene-D-erythritol (13a). Elongation of carbon skeleton of the D-erythrose (14) derived from 13a and then acidic methanolysis gave a mixture of methyl 2,4-dideoxy-4-dimethoxyphosphinoyl-alpha,beta-D-erythropentopyranosides (7), which was led to 2-deoxy-D-ribofuranose phospho sugar (4) in an appreciably improved total yield compared with the procedures via previously reported route. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0385-5414 86 2 2012 Synthesis of 2-Acetamido-2,5-dideoxy-5-phosphoryl-D-glucopyranose Derivatives: New Phospha-sugar Analogs of N-Acetyl-D-glucosamine 1147 1165 EN Tadashi Hanaya Masahiro Kawaguchi Masakazu Sumi Kazuo Makino Keiko Tsukada Hiroshi Yamamoto Starting with N-acetyl-D-glucosamine, methyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-beta-D-xylo-hexofuranosid-5-ulose (18) was prepared in 7 steps. The addition reaction of dimethyl phosphonate to 18, followed by deoxygenation of its 5-hydroxy group, provided the 5-deoxy-5-dimethoxyphosphoryl-D-glucofuranoside derivative (21a). The hydride reduction of 21a, followed by the action of hydrochloric acid and then hydrogen peroxide, afforded the first D-glucosamine analog (23) having a phosphoryl group in the hemiacetal ring. This was converted into the per-O-acetylated N-acetyl-D-glucosamine phospha-sugar (25), while the same treatment of the 5-deoxy-5-dimethoxyphosphoryl-L-idose dimethyl acetal derivative (13b) afforded the N-acetyl-L-idosamine phospha-sugar (29). No potential conflict of interest relevant to this article was reported.

Public Library Science Acta Medica Okayama 1932-6203 7 11 2012 Mitochondrial Localization of ABC Transporter ABCG2 and Its Function in 5-Aminolevulinic Acid-Mediated Protoporphyrin IX Accumulation EN Hirotsugu Kobuchi Koko Moriya Tetsuya Ogino Hirofumi Fujita Keiji Inoue Taro Shuin Tatsuji Yasuda Kozo Utsumi Toshihiko Utsumi Accumulation of protoporphyrin IX (PpIX) in malignant cells is the basis of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy. We studied the expression of proteins that possibly affect ALA-mediated PpIX accumulation, namely oligopeptide transporter-1 and -2, ferrochelatase and ATP-binding cassette transporter G2 (ABCG2), in several tumor cell lines. Among these proteins, only ABCG2 correlated negatively with ALA-mediated PpIX accumulation. Both a subcellular fractionation study and confocal laser microscopic analysis revealed that ABCG2 was distributed not only in the plasma membrane but also intracellular organelles, including mitochondria. In addition, mitochondrial ABCG2 regulated the content of ALA-mediated PpIX in mitochondria, and Ko143, a specific inhibitor of ABCG2, enhanced mitochondrial PpIX accumulation. To clarify the possible roles of mitochondrial ABCG2, we characterized stably transfected-HEK (ST-HEK) cells overexpressing ABCG2. In these ST-HEK cells, functionally active ABCG2 was detected in mitochondria, and treatment with Ko143 increased ALA-mediated mitochondrial PpIX accumulation. Moreover, the mitochondria isolated from ST-HEK cells exported doxorubicin probably through ABCG2, because the export of doxorubicin was inhibited by Ko143. The susceptibility of ABCG2 distributed in mitochondria to proteinase K, endoglycosidase H and peptide-N-glycosidase F suggested that ABCG2 in mitochondrial fraction is modified by N-glycans and trafficked through the endoplasmic reticulum and Golgi apparatus and finally localizes within the mitochondria. Thus, it was found that ABCG2 distributed in mitochondria is a functional transporter and that the mitochondrial ABCG2 regulates ALA-mediated PpIX level through PpIX export from mitochondria to the cytosol. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1881-0942 84 2 2012 First Synthesis of a Natural Isoxanthopterin Glycoside, Asperopterin-A 801 813 EN Tadashi Hanaya Kazumasa Ejiri Hiroshi Yamamoto The key precursor, N-2-(N,N-dimethylaminomethylene)-6-hydroxymethy1-8-methyl-3[2-(4-nitrophenypethyl]-7-xanthopterin (9) was efficiently prepared from 2,5-diamino-6-methylam1no-3H-pyrimidin-4-one (3) and ethyl 3-(tert-butyldimethylsilyloxy)-2-oxopropionate (11). The first synthesis of asperopterin-A (2b) was achieved by treatment of 9 with 1-O-acetyl-2,3,5-tri-O-benzoy1-beta-D-ribofuranose (15) in the presence of tin(IV) chloride, followed by removal of the protecting groups. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 125 2 2013 マウスインフルエンザ肺炎におけるレドックス制御蛋白チオレドキシン（TRX-1）の治療的効果 109 112 EN Masato Yashiro Hirokazu Tsukahara Akihiro Matsukawa Mutsuko Yamada Yosuke Fujii Yoshiharu Nagaoka Mitsuru Tsuge Nobuko Yamashita Toshihiro Ito Masao Yamada Hiroshi Masutani Junji Yodoi Tsuneo Morishima No potential conflict of interest relevant to this article was reported.

Elsevier Science B.V. Acta Medica Okayama 00219673 1288 2013 Determination of association constants between 5 '-guanosine monophosphate gel and aromatic compounds by capillary electrophoresis 149 154 EN Kaori Yamaguchi Nobuyuki Takeyasu Takashi Kaneta Hydro gel formed by 5'-guanosine monophosphate (GMP) in the presence of a potassium ion is expected to exhibit interesting selectivity in capillary electrophoretic separations. Here, we estimated the conditional association constants between the hydro gel (G-gel) and aromatic compounds by capillary electrophoresis in order to investigate the separation selectivity that is induced by the G-gel. Several aromatic compounds were separated in a solution containing GMP and potassium ion at different concentrations. The association constants were calculated by correlating the electrophoretic mobilities of the analytes obtained experimentally using a concentration of G-gel. During semi-quantitative estimation, naphthalene derivatives had larger association constants (K-ass = 10.3-16.8) compared with those of benzene derivatives (K-ass = 3.91-5.31), which means that the binding sites of G-gel match better to a naphthalene ring than to a benzene ring. A hydrophobic interaction was also found when the association constants for alkyl resorcinol were compared with those of different hydrocarbon chains. The association constants of nucleobases and tryptophan ranged from 6.05 to 12.6, which approximated the intermediate values between benzene and naphthalene derivatives. Consequently, the selective interaction between G-gel and aromatic compounds was classified as one of three types: (1) an intercalation into stacked planar GMP tetramers; (2) a hydrophobic interaction with a long alkyl chain; or, (3) a small contribution of steric hindrance and/or hydrogen bonding with functional groups such as amino and hydroxyl groups. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1535-7163 10 9 2011 Liposomal Delivery of MicroRNA-7-Expressing Plasmid Overcomes Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-Resistance in Lung Cancer Cells 1720 1727 EN Kammei Rai Nagio Takigawa Sachio Ito Hiromi Kashihara Eiki Ichihara Tatsuji Yasuda Kenji Shimizu Mitsune Tanimoto Katsuyuki Kiura Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have been strikingly effective in lung cancers harboring activating EGFR mutations. Unfortunately, the cancer cells eventually acquire resistance to EGFR-TKI. Approximately 50% of the acquired resistance involves a secondary T790M mutation. To overcome the resistance, we focused on EGFR suppression using microRNA-7 (miR-7), targeting multiple sites in the 30-untranslated region of EGFR mRNA. Two EGFR-TKI-sensitive cell lines (PC-9 and H3255) and two EGFR-TKI-resistant cell lines harboring T790M (RPC-9 and H1975) were used. We constructed miR-7-2 containing miR-7-expressing plasmid. After transfection of the miR-7-expressing plasmid, using cationic liposomes, a quantitative PCR and dual luciferase assay were conducted to examine the efficacy. The antiproliferative effect was evaluated using a cell count assay and xenograft model. Protein expression was examined by Western blotting. The miR-7 expression level of the transfectants was approximately 30-fold higher, and the luciferase activity was ablated by 92%. miR-7 significantly inhibited cell growth not only in PC-9 and H3255 but also in RPC-9 and H1975. Expression of insulin receptor substrate-1 (IRS-1), RAF-1, and EGFR was suppressed in the four cell lines. Injection of the miR-7-expressing plasmid revealed marked tumor regression in a mouse xenograft model using RPC-9 and H1975. EGFR, RAF-1, and IRS-1 were suppressed in the residual tumors. These findings indicate promising therapeutic applications of miR-7-expressing plasmids against EGFR oncogene-addicted lung cancers including T790M resistance by liposomal delivery. Mol Cancer Ther; 10(9); 1720-7. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 124 3 2012 高分化型ヒト肝癌由来細胞株“HuH-7” 231 238 EN Hidekazu Nakabayashi Kazuhisa Taketa 高分化型ヒト肝癌由来細胞株“HuH-7”は，1982年にCancer Researchにその樹立を報告した．HuH-7は，当時の岡山大学医学部附属癌源研究施設病理部門（故佐藤二郎教授）の下で樹立し，これまで多くの研究分野で利用され，世界的に有名な肝癌細胞株となっている．本稿では，有用性の高い分化機能を有するヒト肝癌細胞株HuH-7について，肝細胞癌の腫瘍マーカーであるα-fetoprotein（AFP）を中心に，この細胞株を用いた研究分野に関する詳細を紹介する． No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 124 3 2012 EGFRチロシンキナーゼ阻害薬耐性肺癌細胞に対するmicroRNA-7発現プラスミドのリポソームを用いた導入による克服の検討 207 210 EN Kammei Rai Nagio Takigawa Sachio Ito Hiromi Kashihara Eiki Ichihara Tatsuji Yasuda Kenji Shimizu Mitsune Tanimoto Katsuyuki Kiura No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 124 3 2012 合成レチノイドAm80はTh1とTh17を抑制することにより慢性移植片対宿主病を改善する 197 201 EN Hisakazu Nishimori Yoshinobu Maeda Mitsune Tanimoto No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 124 2 2012 RXR阻害によるp53-p21^Cip1経路の活性化およびG0/G1細胞周期停止を介した抗肥満作用 97 100 EN Atsuko Nakatsuka Jun Wada Hirofumi Makino No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 124 2 2012 熱ショックタンパク質と抗腫瘍免疫 175 177 EN Shusaku Mizukami No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 124 2 2012 ボツリヌスＡ型菌変異株が産生するHA複合体の構造に関する研究 137 143 EN Shaobo Ma Clostridium botulinum produces seven neurotoxin (NTX) serotypes, classified from as A to G. In culture, NTX forms protein complexes by association with non-toxic components, such as nontoxic-nonhemagglutinin (NTNH) and hemagglutinins (HA1, HA2, HA3). C. botulinum serotype A produces three types of toxin complexes, M-toxin (NTX and NTNH), L-toxin (M-toxin and HAs) and LL-toxin (dimer of L-toxin). In this study, I found three HA complexes in the culture of a nontoxigenic mutant serotype A lacking ntx and ntnh expression. The HA complexes displayed similar banding patterns on SDS-PAGE, but the staining intensities of the HA1 and HA2 bands were different. In addition, their native-PAGE banding profiles exhibited different behaviors. The large-molecular-size HA complex showed the highest activity, similar to that of an L-toxin. Based on the combined results of the PAGE and gel-filtration profiles, the differences in molecular size among the three HA complexes were thought to be caused by different numbers of HA1 and HA2 molecules. This paper reports for the first time the purification and characterization of a native HA complex of serotype A, and suggests that the HA can form complex structures without NTX and NTNH. This may help in understanding the toxin complex assembly pathway. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 124 2 2012 酸化チタン担持セラミックフィルターの光触媒反応による抗菌効果の検討 129 136 EN Miyuki Nakao Titanium dioxide (TiO₂) photocatalysis generates reactive oxygen species such as ・OH and ・O₂-, which can effectively eliminate organic compounds. In the present study, we evaluated the antibacterial and antifungal effects of TiO₂-coated ceramic air filters in both laboratory and hospital settings. Photocatalysis with the TiO₂-coated ceramic filter effectively inactivated all 4 pathogenic organisms tested. Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. After the photocatalysis reaction for 4 h under UV-A (365nm, 250μW/㎠) irradiation, the percentage reductions of the number of E. coli, P. aeruginosa, S. aureus, C. albicans cells were 99.9%, 98.9%, 97.7% and 99.9%, respectively, indicating that Gram-negative bacteria are more susceptible to such photocatalysis than Gram-positive bacteria. Scanning electron microscopic analysis showed damage to the cytoplasmic membrane and cell wall by photocatalysis : consistent with above observations, the morphological change of Gram-negative E. coli was greater than that of Gram-positive S. aureus. 　Further, an air cleaner equipped with a TiO₂-coated ceramic filter significantly decreased the number of bacteria floating in hospitals. 　These results indicate that air cleaners with TiO₂-coated ceramic filters could be useful in reducing the incidence of nosocomial infections. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 124 2 2012 恒常活性型カルシニューリンによる毛周期制御機構―新しい機構に基づく発毛促進ペプチドの開発― 101 104 EN Atsushi Fujimura Kazuhito Tomizawa Hideki Matsui No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 124 1 2012 ニガウリ抽出物の血糖降下作用に関する文献的考察 15 26 EN Mitsumasa Mankura Yasuko Noda Akitane Mori Diabetes mellitus (DM) represents a global health and economical problem. Many patients with DM in Asia, South America, India and East Africa have traditionally used the water extract of unripe fruits of Momordica charantia (bitter melon) as some form of complementary and alternative medicine. Studies of laboratory animals have shown the beneficial blood-glucose lowering and anti-diabetic effects of this remedy. Some oral components that bring lower blood glucose level have been isolated : charantin (sterol glycosides), charantin (polypeptide) and cucurbine-type triterpenes. Part of their actions are related to AMP-activated kinase and repression of the oxidative stress that is increased in DM. Most clinical reports are not fully convincing due to the lack of randomized control studies. The present article reviews the pharmacological and clinical effects of bitter melon with special emphasis on the anti-diabetic effects, and some effects that would require caution in the context of human trials. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 123 3 2011 P-selectin glycoprotein ligand-1 (PSGL-1) 抑制による肥満におけるインスリン抵抗性の改善効果 177 183 EN Chikage Sato No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 123 2 2011 テロメラーゼ依存的腫瘍融解アデノウイルス製剤による 放射線感受性増強作用 103 109 EN Shinji Kuroda Toshiya Fujiwara Yasuhiro Shirakawa Yasumoto Yamasaki Syuya Yano Futoshi Uno Hiroshi Tazawa Yuuri Hashimoto Yuichi Watanabe Kazuhiro Noma Yasuo Urata Shunsuke Kagawa Toshiyoshi Fujiwara DNA修復機能阻害は放射線感受性を増強させるため，DNA修復に関与する因子の阻害剤は放射線増感剤となり得る．我々の開発したテロメラーゼ依存的腫瘍融解アデノウイルス製剤OBP-301（テロメライシン）は，アデノウイルスE1B55kDaタンパクを介して細胞のDNA修復に重要な役割を果たすMRN複合体（Mre11，Rad50，NBS1）を分解する機能を有する．このMRN複合体の分解によりATM（ataxia-telangiectasia mutated）の活性化が抑制され結果的にDNA修復機構が阻害される．我々はOBP-301と放射線との併用が強力な相乗効果を生み出すことをマウスの皮下腫瘍モデルおよび食道癌同所性モデルにおいて証明した．これらの結果はOBP-301が将来有望な放射線増感剤となり得ることだけでなく，E1B55kDaタンパクを産生する腫瘍融解アデノウイルス製剤と放射線との併用が悪性腫瘍に対する有力な治療戦略となり得ることを示す． No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 123 1 2011 アンフィファイジンとN-WASPのダイナミックな相互作用は，アクチン重合を制御する 1 11 EN Hiroshi Yamada Sergi Padilla-Parra Sun Joo Park Toshiki Itoh Mathilde Chaineau Ilaria Monaldi Ottavio Cremona Fabio Benfenati Pietro De Camilli Maïté Coppey-Moisan Marc Tramier Thierry Galli Kohji Takei No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 122 2 2010 TGF-β-Smad3経路と転写因子Sox9による軟骨細胞分化調節 95 99 EN Takayuki Furumatsu Toshifumi Ozaki Hiroshi Asahara No potential conflict of interest relevant to this article was reported.

Elsevier Science B.V. Acta Medica Okayama 0003-2670 620 1-2 2008 A caffeine-sensitive membrane electrode: Previous misleading report and present approach 50 54 EN Takashi Katsu Yumi Tsunamoto Nobumitsu Hanioka Keiko Komagoe Kazufumi Masuda Shizuo Narimatsu Although a previous study [S.S.M. Hassan, M.A. Ahmed, M.M. Saoudi, Anal. Chem. 57 (1985) 1126] had shown that a caffeine-sensitive electrode made with picrylsulfonate and 1-octanol as a cation-exchanger and a solvent mediator, respectively, had a wide working pH range (5.5-9.5) and exhibited a Nernstian response, we could not find such response in this electrode. The present result was reasonable, because the pK, value of caffeinium ion was reported to be around 0.7 and the neutral form of caffeine was predominant in the pH range examined. Thus, we reinvestigated the response characteristics of a caffeine electrode, taking into consideration the pKa value, and constructed a new electrode with a combination of the lipophilic cation-exchanger, tetrakis[3,5-bis(2-methoxyhexafluoro-2-propyl)phenyl]borate (HFPB), and the solvent mediator with high degree of dielectric constant, 2-fluoro-2'-nitrodiphenyl ether (FNDPE). This electrode showed a pH-dependent response to caffeinium ion and gave a detection limit of 50 mu M with a slope of 55 mV per concentration decade at pH 2. The use of other solvent mediators was less effective than that of FNDPE. The electrode was applied for the determination of caffeine in some central stimulants. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 122 1 2010 細胞培養のノーベル賞への貢献 33 38 EN Masayoshi Namba 約1世紀前に, 生きた組織や細胞を動物の体外に取り出した研究―組織培養あるいは細胞培養―が始まった．その後の研究の流れの中で, 1) 組織・細胞培養の特性を生かして行われた研究でノーベル賞に輝いた研究, 2) 組織・細胞培養の経験をもつノーベル賞受賞者, 3) ノーベル賞にはならなかったけれども特記できると私が考える細胞培養の研究，などについて取り上げてみたい. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 122 1 2010 副腎皮質細胞におけるアルドステロンブレイクスルー現象とBMP-6の関与 27 31 EN Hiroyuki Otani Fumio Otsuka Hirofumi Makino No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 122 1 2010 Focal adhesion kinase (FAK) と Insulin-like growth factor-I receptor (IGF-IR) に対するデュアルチロシンキナーゼ阻害剤の食道腺癌における抗腫瘍効果 17 25 EN Nobuyuki Watanabe Munenori Takaoka Kazufumi Sakurama Yasuko Tomono Shinji Hatakeyama Osamu Ohmori Takayuki Motoki Yasuhiro Shirakawa Tomoki Yamatsuji Minoru Haisa Junji Matsuoka David G. Beer Hitoshi Nagatsuka Noriaki Tanaka Yoshio Naomoto No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 122 1 2010 コレクトリンはSNARE複合体との相互作用を介して管腔側膜蛋白の膜輸送を促進し食塩感受性高血圧の発症に関与している 1 7 EN Akihiro Yasuhara Jun Wada Jun Eguchi Atsuko Nakatsuka Kazutoshi Murakami Motoko Kanzaki Sanae Teshigawara Hirofumi Makino 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.

岡山医学会 Acta Medica Okayama 0030-1558 121 3 2009 特異的プロモータを用いた目的遺伝子発現システムの開発と癌治療への応用 157 162 EN Takuya Fukazawa Junji Matsuoka Tomoki Yamatsuji Noriaki Tanaka Yoshio Naomoto No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 121 3 2009 Dravet 症候群患者に認められたカルシウムチャネル　機能異常を引き起こす CACNB4 遺伝子変異 149 156 EN Iori Ohmori Mamoru Ouchida Nobuyoshi Mimaki Teiichi Nishiki Kazuhito Tomizawa Hideki Matsui No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 121 3 2009 DNAトポイソメラーゼⅡβによる神経関連遺伝子の活性化機構 143 147 EN Kuniaki Sano Mary Miyaji M. Kimiko Tsutsui Ken Tsutsui No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 121 2 2009 抗体医薬 119 122 EN Hidenori Wake No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 121 1 2009 Des-γ-carboxy prothrombinは血管内皮細胞の増殖能と移動能を亢進させる 1 8 EN Tatsuya Fujikawa Hidenori Shiraha Kazuhide Yamamoto No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 103 11-12 1991 高濃度分岐鎖アミノ酸を窒素源とする成分栄養剤の侵襲下における効果―肝切除ラットを用いて― 1287 1299 EN Minoru Mizuta The nutritional influence of branched chain amino acids (BCAA) and lipids in surgical stress was examined after 70% hepatectomy in rats. Two types of elemental diet (ED) were given through the gastrostomy tude for 7 days. Group A : ED containing 33% BCAA and 30% lipid (medium chain triglycerides 8.5g＋soy bean oil 1.5g/300 kcal). Group B : ED containing 17% BCAA and 1.5% lipid (soy bean oil 0.49g/300 kcal). Up to the 7th postoperative day, the excretion of nitrogen into urine decreased in group A, but no change occurred in group B. Up to the 5th postoperative day, molar ratio of 3MH to creatinine in urine in group A decreased more rapidly than in group B. Plasma concentration of albumin in group A was higher than in group B on the 7th postoperative day. Fischer ratio was significantly higher in group A than in group B on the 7th postoperative day. Both plasma and muscle levels of Tyr, Met and Gln were higher in group B than in group A, Glu and Ala were lower in group B than in group A. Essential fatty acid deficiency occurred more severely in group B than in group A. While fatty livers were microscopically observed in some livers in group B, there were few fatty deposits in group A. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 102 3-4 1990 頑痛の発生および抑制に関する基礎的・臨床的研究　第1編　三叉神経脊髄路尾側亜核におけるサブスタンス P およびエンケファリン濃度変動の意義に関する基礎的研究 287 297 EN Noriaki Fujiwara The possible role of substance P (SP) and enkephalin (ENK) was investigated in the mechanism of deafferented pain (DP) and excess pain. The concentration of SP anf ENK was quantitatively estimated with radioimmunoassay using 17 adults cats. The animal were divided into 3 group, DP group (8 cats), EP group (6 cats) and untreated conrol group (3 cats). The DP group was prepared according to the method described by Shimizu and EP model was made by injection 1 ml of Freund's adjuvant subcutaneously into the unilateral face of the cats every day for 3 weeks. The amount of SP in STN markedly decreased in DP group and significantly higher in EP group than with the control group. This is explained by the fact that SP is a neurotransmitter for pain of trigeminal nerve. No significant decrease in ENK in the DP group was observed. This suggests that ENK in STN is not always controlled by the descending inhibitory system, but may be working in the propriospinal system. ENK in the EP group also showed no significant increase. This can be explained not only by the difficulty in estimating the rapid degeneration of ENK, but also by the strong participation of monoamines as well as ENK in pain relief. The role of ENK should not be overstimated and the studies including monoamines will be necessary to detemine the mechanism of pain. 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 内在性小胞体内 A 粒子の構成蛋白に関する研究ーアデノウイルス12型誘発マウス腫瘍に認められた粒子についてー 199 207 EN Eiichiro Hirakawa Analysis and purfication of structural proteins of intracisternal A particles produced in adenovirus-induced tumor were described. SDS-PAGE of purified intracisternal A particles demonstrated its major structural components, K92, K70 and K55, and minor components, K43 and K37. Two dimensional gel electrophoresis indicated a pI of K70 and K55 at 6.5 and 6.3, respectively, in the presence of sodium dodecyl sulfate. Purification of the main band, K70, in SDS-PAGE using reversed phase-HPLC was difficult in the standard acidic condition, but could be achieved in the neuttral condition. Although purificatin of K70 is generally difficult because of its hydrophobicity, the method shown here will be useful for furthey study of structural proteins of intracisternal A particles. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 103 11-12 1991 脂肪（MCT）および高濃度分枝鎖アミノ酸を含有した成分栄養剤の侵襲下における効果 1253 1265 EN Kazunaga Suehiro The effects of a new enteral diet (ED-9) that was mainly composed of BCAA enriched amino acids, MCT and maltose were examined. Rats were subjected to small bowel resection and were administered two different formula for 7 days. The animals were divided into the following four groups : Sham operation and ED-9 (Group A), sham operation and control diet (Elental) (Group B), small bowel resection and ED-9 (Group C), and small bowel resection and control diet (Group D). Body weight loss after operation was similar in both ED-9 and control diet groups. Nitrogen balance and uninary 3 Methy1-histidine excretion demonstrated that ED-9 tended to improve protein preservation. Rats given ED-9 showed elevated ketone bodies and plasma BCAA level but these levels were not extraordinarily high. In conclusion, the formula of enteral nutrition (ED-9) was as effective as Elental on postoperative nutrition in rats. 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 102 1-2 1990 一過性虚血後の慢性期ラット脳における生化学的変化に検する研究 129 141 EN Hiroshi Yoshikawa In recent years, cases of sequelae of cerebrovascular disease such as vascular dementia due to death of many neurons have been increasing. Such neuronal death following brain ischemia had been considerd to be due to an energy deficiency resulting from an impaired respiratory chain. However, the detection of the delayed neuronal death showed that neuronal death is not caused by mere energy deficiency. Most previous studies on delayed neuronal death focused on the changes in morphology and energy metabolism in the acute to subacutte stage. There are few reports concerning biochemical changes in the chronic stage, especially in neurotransmitter receptors. Transient ischemia for 20 minutes in a rat four-vessel occlusion model was induced, and serial histological and biochemical changes were evaluated until the chronic stage. Destruction of pyramidal cells in the CAI area of the hippocampus was completed by 10 days after cerebral ischemia followed by recirculation of cerebral blood flow. Light microscopy showed no progression after this day. The level of acetylcholine (ACh) was significantly decreased in the hippocampus, striatum, and frontal cortex at the termination of ischemia but recovered to normal 21 days after recirculation of cerebral blood flow. The binding sites of muscarinic ACh receptors (mACh-R) per usit of protein were increased in the hippocampus 21 days after recirculation of blood flow. However, no changes were observed in the total number of mACh-R in the entire hippocampus. Thuse finings suggest no changes in the ACh neuronal system in the chronic stage and no direct association between this ayatem and delayed neuronal death. On the other hand, N-methyl-D-aspartate (NMDA) receptors, a subtype of glutamate receptirs, showed no change in the hippocampus until after 10 days, but decreased to half after 21 days despite no evidence of histological progression of neuronal death. Thus, delayed neuronal death after transient forebrain ischemia appears to be deu to release of glutamate, an excitatory amino acid. Our findingd show the specific death of neurons with NMDA receptors for glutamate. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 103 11-12 1991 体外循環下における心筋の虚血再灌流に関する検討-h-SOD の効果と至適投与量- 1225 1235 EN Yukio Yamada The efficacy of recombinant human superoxide dismutase (h-SOD) was examined and its optimal dose when given before reperfusion in an experimental canine cardiopulmonary bypass (CPB) model was determined. Mongrel dogs were placed on total CPB for 130 minutes without aortic cross clamping (Group Ⅰ). Others were placed on CPB for 120 minutes aortic cross clamping with intermittent administration of cardioplegic solution and core cooling (Group Ⅱ). Before reperfusion, saline, and 1 mg, 3 mg, 10 mg and 20 mg h-SOD per kilogram were administered via the aortic root as a bolus injection (Group Ⅲ,Ⅳ,Ⅴ,Ⅵ,Ⅶ). Reperfusion after hypothermic global ischemia with aortic cross clamping deteriorated cardiac function (cardiac index, left ventricular maximum dp/dt), increased myocardial water content and increased cardiac enzyme release (creatinine kinase MB isozyme, α-hydroxybutyric dehydrogenase). Administration of 3 mg/㎏ h-SOD significantly ameliorated this reperfusion injury, protected myocardial function early after CPB and gave a desirable peak serum h-SOD concentration. 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 4 1991 日本人ヒポカタラセミア, マウスヒポカタラセミア, マウスアカタラセミアの血球カタラーゼの比活性度 305 313 EN Yasuhito Fujii Blood catalase was purified by CM-cellulose followed by DEAE-cellulose and Sephadex G-150 from blood of Japanese individuals. Rabbit was injected with purified blood catalase emulsified wiwth Freund complete adjuvant. Blood was taken after 6 injections, serum was separated as anti-Japanese blood catalase rabbit serum, and was used for the immunotitration of blood catalase from hypocatalasemic and normal Japanese. Liver catalase was purified twice from the ammonium sulfate fraction of mice liver supernatant by using the same Sephadex G-200 column. In the same way as for humans, the rabbit was immunized and serum was taken as anti-mice liver catalase tabbit serum, and was used for the immunotitration of blood catalase from acatalasemic, hypocatalasemic and normal mice. Specific activity of catalase in the blood of the hypocatalasemic Japanese was determined by immunotitration. That activity was the same as that of catalase in the blood of normal Japanese individuals. In contrast to this, the specific activity in the blood of hypocatalasemic mice was lower than that of normal mice. Specific activity of residual catalase in the blood of acatalasemic mice showed the lowest value among the activities in the blood of normal, hypocatalasemic and acatalasemic mice. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 103 4 1991 心筋虚血・再灌流障害における過酸化脂質の動態と h-SOD 投与効果 293 303 EN Eiji Ikeda To clarify the role of free radicals and the efficacy of human superoxide dismutase (h-SOD) on cardiac ischemia/reperfusion injury, adult mongrel dogs were placed on a cardiopulmonary bypass (CPB). Aorta was cross clamped for 120 minutes and crystalloid cardioplegic solution was administered into the aortic root every 30 minutes. Sixteen dogs were divided into the control group and non cross clamped group (XCL(-)group). They were placed on total CPB for 130 minutes without an aortic cross clamp. The control group showed higher thiobarbituric acid reactive substance (TBARS) release from heart in early reperfusion phase (P<0.05), and suppressed recovery of cardiac index (CI) and max dp/dt at 60 minutes after reperfusion (P<0.01 and P<0.05, respectively) than XCL (-) group. Eight dogs were administered saline and 32 dogs were administered saline and h-SOD into the aortic root just before reperfusion. Dogs, administered h-SOD, were devided into four groups by the dese of h-SOD, group I : 1mg/kg, group II : 3mg/kg, group III : 10mg/kg, and group IV : 20mg/kg. Between control and saline groups, no significant difference was found. Groups I and II showed suppressed TBARS release from the heart in the early reperfusion phase than the control group (P<0.01 and P<0.05, respectively). Groups II and III showed higher recovery of CI at 60 minutes after reperfusion than the control group (P<0.01 and P<0.05, respectively). In conclusion, significantly higher TBARS was released from the heart and recovery of cardiac function was suppressed in cardiac ischemia/reperfusion injury. The h-SOD administtation was effective to protect the heart from cardiac ischemia/reperfusion injury. 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 エンドトキシン投与ラットにおける肝内メタロチオネイン遺伝子発現に関する研究 625 637 EN Naoyuki Taga To clarify the functions of hepatic metallothioneins (MTs) after the administration of endotoxin (lipopolysaccharide : LPS), we investigated the expression on MT genes in the bacterial endoxin-treated rat liver by Norhern blot hybridization and in situ hybridization methol with riboprobes synthesized from mouse cDNA of MT-Ⅱ chronologically. Northern blot analysis revealed a rapid increase in the amount of MT gene transcripts in the liver 3 hours after the administration of LPS, with a maximum at 6 to 12 hours followed by a gradual decrease. In the in situ hybridization method, MT genes are expressed in the liver lobule for 3 hours after the adiminstration of LPS, and hepatocellular damage was observed at 6 hours after the LPS administration initially and expanded most extensively at 18 hours. During this peripd, MT genes are expressed in intact tissue intensely and specifically. At 24 hours after the administration, transcripts of the MT gene were detected in intact hepatocytes around the shrinking necrotic area. These findings suggest that MTs protect the liver cells by scavenging the free radicals, which probably cause liver cell damage due to LPS administration, and that MTs provide the zinc ions necessary for stabilizing the cell membrane and to heal the liver cell damge. 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 アスコルビル酸による 1,25dihydroxyvitaminD(3) 作用の増強―培養ヒト骨肉腫細胞 MG63 における検討― 617 624 EN Makoto Kurihara We eximined the interaction between 1,25-dihydroxyvitamin D(3) and ascorbic acid in the human osteosarcoma cell MG63 by measuring alkaline phosphatase (ALP) activity. Both vitamins induced ALP activity in this cell line. Simultaneous addition of both ascorbic and 1,25-dihydroxyvitamin D(3) induced much higher ALP activity than each vitamin alone. Pretreatment of MG63 with ascorbic acid or type I collagen, increased the ALP activity induced by 1,25-dihydroxyvitamin D(3). Binding assay anf immunoblotting analysis showed that the number of vitamin D receptors was increased in MG63 pretreated with ascorbic acid. In conclusion,ascorbic acid stimulates collagen production of MG63, and collagen increases the vitamin D receptor content. The increase in vitamin D receptor content potentiates the activity of 1,25-dihydroxyvitamin D(3) in this cell line. 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 103 1-2 1991 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)　を用いたパーキンソニズム・モデルマウスにおける脳内神経ペプチドに関する研究 105 116 EN Makio Kawata 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) has been shown to destroy the nigrostriatal dopaminergic system, inducing biochemical and histopathological changes resembling Parkinson's disease. Biochemical changes, especially changes of neuropeptides were determined 1,2 or 6 weeks after MPTP treatment in various regions of the mice brain. The dopamine (DA) concentration decreased to 22% of the control level in the striatum 1 week after MPTP treatment, but recovered to 50% of the control level 6 weeks after MPTP treatment. The decrease in the noradrenaline concentration was less than that of DA. Amine fluorescence histochemistry revealed, markedly decreased amine fluorescnece in the striatum 6 weeks after MPTP treatment, and this decrease in amine fluorescence was recovered after levodopa treatment. The results of a pole thst revealed the bradykinesia of MPTP-treated mice and it was attenuated b y levodopa and amantadine hydrochloride treatments. Among the neuropeptides tested, somatostatin (SOM) increased 1 week after MPTP treatment in the striatum and the thalamus＋midbrain but decreased 6 weeks after MPTP treatment in the striatum and the hippocampus. In the striatum the decreased SOM recovered with levodopa treatment. Thus, the SOM might be regulated by a dopaminergic system. On the other hand, in the cerebral cortex, while no changes appeared in the SOM concentration after MPTP treatment, the concentration decreased significantly with levodopa treatment. Other neuropeptides such as substance P, cholecystokinin-octapeptide and thyrotropin releasing hormone did not show any significant changes up to 6 weeks after MPTP treatment. 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 肺癌患者における血清酵素 Leucine Aminopeptidase (LAP) Isozyme の研究 517 537 EN Tetuo Okazaki Serum leucine sminopeptidase (LAP) activity and its isozyme fraction were assayed in 73 primary lung cancer patients with the passage of time before the operation to 3 years after the operation. The LAP activity showed a high value in 25% of the patients before the operation, but did not exhibit a significant change after the operation. By contrast, the isozyme Y fraction showed a high value in 71% of the patients before thee operation and normalization was observed in half of them 1 month after the operation. There was no significant difference in the Y fraction with the size of tumor before the operation, but a significant fall wes observed after curative resection. About half of the patients in whom the Y fraction showed a high value before the operation died within 1 year after the operation. Furthemore, the subsequent prognosis was unfavorable evan in patients in whom the value was normalized after the operation, and a high Y fraction value before the operation seemed to serve as a parameter of unfavorable prognosis. 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 セボフルレン麻酔の Minimum Alveolar Concentration (MAC) に及ぼす血漿蛋白と笑気の影響に関する実験的研究 41 51 EN Masato Maeta The effects of plasma protein concentration (TP) on sevoflurane plasma protein/gas partition coefficient and of hematocrit values (Ht) on sevoflurane red cell/gas partition coefficient were examined in dogs. Furthermore, the effects of TP and inhalated nitrous oxide on sevoflurane MAC and sevoflurane concentration in blood at 1 MAC were studied in dogs during sevoflurane anesthesia. Snginificantly posotive correlations were noted in vitro between TP and plasma/gas partition coefficient, and between Ht and red cell/gas partition coefficient. However, the change in blood/gas partition coefficient appeared to be affected by TP. Sevoflurane MAC and seveflurane concentration in blood at 1 MAC rose in positive correlation with the rise of TP with or without nitrous oxide in combination, but there was no correlation with Ht. This seemed to be related to the predominancy of sevoflurane to dissolve into the plasma. The sevoflurane MAC and sevoflurane concentration in blood were significantly lower in the 33% nitrous oxide combined group than those in the oxygen alone group, but there was no significant difference between the 66% nitrous oxide combined group and the 33% nitrous oxide combined group. Furthermore, TP affected the sevoflurane MAC but not the nitrous oxide MAC. 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 トリプトファン代謝産物のラット脳機能に対する影響の研究 471 482 EN Yutaka Nishijima The effects of tryptophan (Trp) metabolites administered into right cerebroventricle (1μmol) on the electrocorticograms (ECoG) of rats were studied to investigate the roles of Trp metabolites in the brain function. Kynurenine, anthranilic acid, and xanthurenic acid has no effect on ECoG until the end of recording 4 hours after the administration. 3-Hydroxykynurenine had a suppressive effect on the ECoG transitory, and kynurenic acid suppressed ECoG slightly. 3-Hydroxyanthranilic acid which is a metabolite of 3-hydroxykynurenine, induced spike discharges with a long latency (60-230 min after the administration). 3-Hydroxyanthranilic acid is thought to be metabolized to o-aminophenol, quinolinic acid and picolinic acid. Among the 3-hydroxyanthranilic acid metabolites, o-aminophenol induced spike discharges a few min after the administration, and the spike discharges a few min after the administrations, and the spike discharges lasted 60 min. On the other hand, quinolinic acid suppressed ECoG, and picolinic acid had no effect. These electrocorticographic findings suggest that 3- hydroxyanthranilc acid might induce spike discharges after metabolization to o-aminophenol. 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 ヒト血小板凝集能におけるセロトニン(2)およびアルファ(2)-アドレナージック受容体の薬理学的相互作用 1005 1012 EN Hidetoshi Okada To investigate the interaction between serotonin (5HT)(2) and α(2)-adrenergic receptors in the human platelet membrane, the inhibitory effects of calcium (Ca) antagonists, 5HT(2) antagonists, α(2) antagonists and adenosine (AE) receptor (A(2)) agonists on 5HT plus ADP ([5HT＋ADP]) and adrenaline (ADR) plus ADP ([ADR＋ADP])-induced washed platelet aggregation were examined. In the [5HT＋ADP] -induced aggregation. The inhibitory activity was in the order of (－)-desmethoxyverapamil (D888), mianserin (MA), ketanserin, AE>diltiazem, nicardipine, yohimbine. On the other hand, in the [ADR＋ADP] -induced aggregation, the inhibitory activity was in the order of MA, YH>D888, AE, and the rest had no significant effect even at 10 μM. Only AE among these drugs inhibited ADP-induced aggregation. The present findings indicate that the Ca antagonist D888, 5HT(2) antagonist MA and α(2) antagonist YH acted simultaneously as 5HT(2) and α(2) receptor inhibitors and imply an apparent interaction between these receptors. Since both of the aggregation responses required extracellular Ca(2+) and were modulated by Ca(2+) concentrations, the mechanism of interaction may be attributed to intracellular Ca(2+)-signaling systems. 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 104 3-4 1992 鉄代謝におけるマクロファージのトランスフェリンレセプターに関する研究　第2編　鉄過剰及び鉄欠乏状態における肺胞マクロファージのトランスフェリンレセプターに関する検討 387 398 EN Toshio Inada Transferrin receptors (TfR) are involved in the first step of iron uptake into cells. To clarify the changes in TfR under various conditions, radiobinding assay of (125)I-labeled iron-saturated transferrin was performed in alveolar macrophages from 2 patients with idiopathic hemo-chromatosis and iron-overloaded or iron-deficient guinea pigs. Patients with idiopathic hemochromatosis showed a reduction in the Fe-TfR count on alveolar macrophages (5.0×10(4)/cell) as compared to that in healthy individuals (19.88±8.19×10(4)/cell). Concerning the Fe-TfR binding constant, no differnce was observed between patients with idiopathic hemochromatosis and healthy controls. The Fe-TfR count on alveolar macrophages was significantly lower in iron-overloaded guined pigs than in normal cntrols. The count was significantly elevated in iron-deficient guinea pigs. Concerning the Fe-TfR binding constant, none of the iron-overloaded and iron-deficient groups showed any significant difference from the normal controls. These findings suggest that experimentally-induced iron overload and iron deficiency may be autoregulated by intracellular iron levels. 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 鉄代謝におけるマクロファージのトランスフェリンレセプターに関する研究　第1編　各種マクロファージにおけるトランスフェリンレセプターの局在に関する検討 375 386 EN Toshio Inada The delivery of iron into cells is mediated by transferrin via its receptors that reside on the cell surface. To clarify the role of reticuloendothelial cells in iron metabolism, the distribution of transferrin receptors on macrophages in various organs and on peripheral blood monocytes was examined by scanning electron microscopy and radiobinding assay. Radiobinding assay of human alveolar macrophages revealed the presence of 19.88±8.19×10(4) diferric trabsferrin receptors per cell (mean±SD) and a binding constant of 4.42±3.41×10(8)M(-1). Human peritoneal macrophages and macrophages in the thoracic cavity had fewer diferric transferrin receptors (2.68×10(4), 8.10×10(4), 4.3×10(3) and 2.1×10(4) receptors/cell). Peripheral blood monocytes had no diferric transferrin receptors. Diferric transferrin receptors were also found on guinea pig alveolar macrophages (2.25±0.78×10(4)) and peritoneal macrophages (1.6±0.2×10(3)), while they were absent on rat alveolar and peritoneal macro-phages. Scanning electron microscopic findings in guinea pig alveolar macrophages revealed a patch-formed distribution of apotransferrin receptors and diferric transferrin receptors on the characteristic ruffle-covered surface of macrophages. The number of transferrin rece-ptors varied among individual cells even within the same species or same organs. These findings suggest that the macrophages with transferrin receptors in various organs of human and guinea pigs are heterogeneous among different species and cells, and have different functions in iron metabolism. 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 慢性関節リウマチにおける Superoxide Dismutase (SOD) 活性の測定と臨床的意義に関する研究 355 364 EN Jinichi Onoue In chronic inflammations of rheumatoid arthritis (RA), polynuclear leukocytes, macro-phages, synovial cells and other inflammatory cells release reactive oxygen species (ROS) and cause tissue impairment, and are regarded as the responsible agents in this pathological condition. In the present study, the electron spin resonance (ESR) method was used to measure superoxide dismutase (SOD) in 76 knee synovial fluid samples from rheumatoid knee joints and to compare the results with those of osteoarthritic knee joints and postraumatic arthritis. There was no significant difference in the SOD activity between PA and OA patients knee joint fluid, which was higher than that in patients with posttraumatic arthritis. The SOD activity in RA knee joint fluid showed no correlation with serum CRP (C-reactive protein) or erythrocyte sedimentation rate, indices of inflammation. According to Larsen's Grading of rtheumatoid knee radiography, patients with moderate RA changes (grade Ⅲ or Ⅳ) show higher SOD activity than patients with early (grade Ⅰ or Ⅱ) and terminal RA (grade　Ⅴ). Our findings suggest that the SOD actvity in RA knee joint fluid is a valid index of articular destruction. 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 尿路感染症患者分離 Proteus mirabilis の病原性発現因子の解析 963 972 EN Katsuhisa Murotani Proteus mirabilis has several pathogenic factors such as adherent ability to urinary tract epitherial cells, urease, motility and resistance to urine. The pathogenic activities of clinically isolated P. mirabilis were analyzed. Higher pathogenic strains (No. 25 and No. 30) which had morphologically different pili but had a higher density of pili showed strong adherent activity to bladder epithelial cells of mouse and rat. These strains also showed a clear chemotaxis to urinary tract tissue extracts. These findings indicate that the combination of adherent, chemotaxis and urease activities is essential for causing of tipical kidney infection by P. mirabilis. 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 1,25-DihydroxyvitaminD(3)によるヒト骨肉腫細胞 MG63 からのinsulin-like growth factor binding protein 3 の産生増加 323 330 EN Tadashi Moriwake Several types specific insulin-like growth factor binding proteins (IGFBPs) are produced by peripheral tissue-derived cells and they modulate the functions of insulin-like growth factors. In this study, both the secretion of IGFBP-3 from a human osteosarcoma cell line MG63 and effects of 1, 25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) on the production of IGFBP-3 were investigated. The β subunit of IGFBP-3 was detected immunocytochemically in the perinuclear cytoplasm of MG63 cells. Immunoblotting and SDS-PAGE analysis revealed that both 140-150KD MW entire molecules and 40-60KD MW β subinit molecules of IGFBP-3 were present in cell-conditionel media. 1,25-(OH)(2)D(3) stimulated the production of the IGFBP-3 molecule by MG63 cells. The concentration of IGFBP-3 conditioned media began to rise at 24 hours after the addtiton of 10(-9)M of 1,25-(OH)(2)D(3) and reached the peak level at 48 hours. Dose-dependent effects of 1,25-(OH)(2)D(3) were demonstrated. These findings show that MG63 produces IGFBP-3 and that 1,25-(OH)(2)D(3) stimulates the production of this protein. These findings suggest that the synergistic effects of 1,25-(OH)(2)D(3) on the action of IGF-I on osteoblastic cells may be modulated by locally produced IGFBP-3. 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 コバルト誘導てんかん性大脳皮質のサイクリック AMP 合成系に関する研究 951 962 EN Hideki Asaki A cobalt chloride solution was injected into the unilateral sensorimotor cortex of rats to induce epileptic activity. The cyclic AMP contents of slices incubated with or without adenosine and 2-chloroadenosine were determined in four cortical areas after electroencephalography and behavioral examination in cobalt-injected rats. Electrographic spike activity appeared immediately after injection of cobalt. In the majority of cobalt-injected rats, the spike activity was dominant in the primary epileptic region of the cortex. The spike frequency reached a maximum level two to three weeks after the injection and declined thereafter. The electrographic activity was followed by abnormal behavior. Adenosine and 2-chloroadenosine elevated the cyclic AMP levels in the cortical slices 6-to 10-fold and 10-to 16-fold, respectively. The elicitation of cyclic AMP accumulation was strongly inhibited by the adenosine antagonist 8-phenyltheophylline. The cyclic AMP accumulation elicited by adenosine or 2-chloroadenosine was increased in the primary cortical area of cobalt-induced epilepsy, but in the other cortical areas there was no deviation in cyclic AMP accumulation. The increase in cyclic AMP accumulation was observed regardless of the presence or absence of the adenosine uptake inhibitor dipyridamole, phosphodiesterase inhibitor Ro 20-1724, and adenosine deaminase. The increased accumulation of cyclic AMP in the primary epileptic cortex was detected as early as 8 days after the injection. The cyclic AMP accumulation slightly increased thereafter. It reached a plateau 17 to 19 days after the injection and then turned to the control levels, in harmony with the electrographic and behavioral profiles. These findings suggest that alterations in adenosine-sensitive generation of cyclic AMP in the primary epileptic region of the cortex are part of the neurochemical process of cobalt-induced epilepsy. 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 高速液体クロマトグラフィーによる中国野菜中のアスコルビン酸および総アスコルビン酸の定量 899 903 EN Yoshihiro Shimada Sanae Ko Masana Ogata A Simple high-performance liquid chromatographic method is described for the rapid estimation of ascorbic acid and total ascorbic acid. Use of tetra-n-butylammonium bromide as an ion-pairing reagent in the mobile phase yielded reproducible retention for ascorbic acid. Total ascorbic acid is determined by reducing the dehydroascorbic acid to ascorbic acid by treatment with DL-homocysteine. This high-performance liquid chromatographic method has been applied to the analysis of several Chinese vegetables. These Chinese vegetables contained more total ascorbic acid than any other vegetables on the market. 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 モノアミン代謝酵素活性に及ぼすグアニジノ化合物の影響に関する研究 1093 1105 EN Katsuhisa Hukuyama In the central nervous system (CNS)of mammals, monoamine oxidase (EC 1.4.3.4)(MAO), which have been divided into two functional forms (MAO-A and MAO-B), and catechol-O-methyltransferase (EC 2.1.1.6)(COMT) act as catabolic enzymes of catecholamines and serotonin regulating their concentrations. In this study, the effects of guanidino compounds (5mM) on MAO-A, MAO-B and COMT were examined to invastigate the role of guanidino compounds in CNS function. MAO-A activity was decreased by α-guanidinoglutaric acid (GGA) and guanidinoethanesulfonic acid, and increased by arginine (Arg) and N-acetylarginine at a low substrate concentration (4.33μM). MAO-B activity was decreased by creatinine (CRN), δ-guanidinovaleric acid (GVA) and methylguanidine (MGua) at a high substrate concentration (3.125mM), and decreased by CRN, GVA, MGua, Arg, guanidine, 2-guanidinoethanol, β-guanidinopropionic acid, guanidinosuccinic acid and homoarginine at a low substrate concentration (62.5μM). GVA, CRN and MGua acted as competitive inhibitors on MAO-B and their calculated Ki values were 9.47mM, 14.5mM and 29.4mM, respectively. Although the guanidino compounds tested had no effect on COMT activity at a high substrate concentration (600μM), GSA and GVA inhibited COMT activity at a low substrate concentration (75μM). These results suggest that some guanidino compounds influence catabolic enzymes of indoleamine and catecholamines to control CNS function. 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 気管支喘息の血小板機能に関する研究 第2編 喘息患者血小板の12-HETE 産生能とリンパ球機能に及ぼす影響に関する検討 1079 1086 EN Koji Sunami To clarify the role of platelets in the pathogenesis of bronchial asthma, the production of 12-hydroxyeicosatetraenoic acid(12HETE) from platelets of asthmatics was examined by high performance liquid chromatography(HPLC). The effect of platelets on lymphocyte function was also studied by lymphocyte blastogenesis. The results were as follows : 1) The production of 12HETE from platelets of asthmatics were significantly higher than that of normal subjects(p<0.01). 2) Blastogenesis of lymphocytes was significantly suppressed by addition of platelets(p<0.05). 3) Blastogenesis of lymphocytes was significantly suppressed by addition of more than 12.5ng/ml of 12HETE, 10ng/ml of transforming growth factorβ(TGE-β) or 50ng/ml of serotonin. These results suggest that platelets play an important role in the pathogenesis of asthmatic responses mediated by activated lymphocytes. 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 骨髄異形成症候群におけるヒト赤芽球トランスフェリン受容体発現に関する研究　第2編　骨髄異形成症候群におけるトランスフェリン受容体発現の特徴について 879 888 EN Ritsurou Tsuyuno Expression of TfR on the cell surface is known to be regulated by the cellular iron content. We previously reported an inverse correlation between mean number of TfR expressed and stainable iron granules (SIGs) of erythroblasts (EBLs) in normal subjects. In MDS, EBLs contain an increased number of SIGs, though the mechanism of this phenomenon is not well understood. In this report, expression of surface transferrin receptor (TfR) on bone marrow EBLs was examined in comparison with the number of SIGs in 11 patients with myelodysplastic syndrome (MDS) and 11 patients with acute leukemia (AL). The mean numbers of TfR from MDS (5.56±1.35x10(5)) and AL (5.73±2.25x10(5)) were not different from those of normal subjects (5.00±1.80x10(5)). However, in MDS the mean number of TfR from 8 patients (72%) was similar to the normal level in spite of the increased mean number of SIG. Four of the 11 patients with AL showed a similar change such as MDS in TfR, but notably 2 of those 4 patients were AL transformed from MDS. There is a correlation (r＝0.61) between TfR and MCV in MDS different from that in healthy subject. These findings suggest that TfR expression on EBLs, from MDS may escape from the regulation by the cellular iron content as iron-TfR regulation disturbance. 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 気管支喘息の血小板機能に関する研究 第1編 喘息患者血小板の形態変化とセロトニン遊離能の検討 1069 1078 EN Koji Sunami To calrify the role of platelets at the site of allergic reaction, ultrastructural observation, measurement of plasma serotonin levels and serotonin-releasability of platelets after various stimuli were studied in 29 asthmatics and 6 normal controls. The results were as follows : 1) Plasma serotonin levels were higher during the attack stage than non-attack stage in asthmatics. 2) Morphological changes and the aggregation of platelets were observed by scanning electron microscopy after stimulation with platelet activating factor(PAF), CaI, anti-IgE and anti-IgG. 3)The serotonin-releasability of platelets stimulated by CaI was significantly decreased in severe asthmatics, compared with mild asthmatics and normal subjects(p<0.05). However, there were no significant differences between steroid dependent and non-steroid dependent intractable asthmatics in severe asthma. 4) The releasability of serotonin was decreased in most cases during asthmatic attack and was suppressed by aminophyllin. 5) The serotonin-releasability of platelets stimulated by anti-IgG of Candida antigen was remarkably enhanced aftre incubation with serum, although releasability was not increased with heart-treated serum. These results suggest that platelets play an important role in bronchoconstriction induced by various immunological reactions involved with complement activation in the pathogenesis of bronchial asthma. 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 ハロタンのラット肝ミクロソーム中チトクロームP-450に及ぼす影響 1033 1046 EN Yukio Ido Hepatic microsomes were collected from male rats in which hepatic microsomes enzymes were induced by phenobarbital (PB) and untreatend rats. Microsomes were deoxygenated by vacuum-freezing and exposed to 2% or 10% halothane and then incubated in a 37℃ bath for 5 or 20 minutes. Microsomal enzyme contents and enzyme activities were measured. The contents of cytochrome P-450 were decreased in PB-induced microsomes (PB-microsomes) and the decrease wes greater with 10% halothane or 20-minute incubation than with 2% halothane or 5-minute incubation. The contents of cytochrome P-450 in non-PB-microsomes were also decreased by 10% halothane. Heme contents were decreased in PB-microsomes by 10% halothane, and in non-PB-microsomes by 20-minute incubation with 2% halothane. The activities of aminopyrine demothylation were decreased both in PB and non-PB-microsomes and the decrease was greater with 10% halothane. The activities of aniline hydroxylation were decreased in PB and non-PB-microsomes, and after 20-minute incubation. The contents of cytochrome b(5), the tetrabutylic acid reacting substances and the activities of cytochrome P-450 reductase were not changed. The decreases of microsomal cytochrome P-450 and microsomal enzyme activities by halothane exposure in deoxygenated states might be related to hepaitc injury following halothane anesthesia. 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 骨髄異形成症候群におけるヒト赤芽球トランスフェリン受容体発現に関する研究　第1編　赤芽球トランスフェリン受容体発現に及ぼす形態，成熟度，ヘモグロビン濃度，可染性鉄顆粒数の影響について 869 877 EN Ritsurou Tsuyuno Erythroblasts (EBLs) as well as thrombocytes and myelocytes show changes in patients with myelodysplastic syndrome (MDS). The changes include increse in sideroblasts and maturation delay. Expression of the transferrin receptor (TfR) has been known to correlate with stainable iron and cell maturation. To clarify whether the regulation mechanism of TfR on bone marrow EBLs is altered in MDS and acute leukemia (AL), TfR expression on EBL from MDS and AL were measured in individual cells as well as cell morphology, stainable iron granules (SIGs) in EBLs and cellular hemoglobin content using the morphometric method established in our laboratory. Generally, the number of TfR and density of TfR on EBLs decreased along with cell maturation. The density of TfR was negatively correlated with hemoglobin concentration (r＝－0.76), but SIGs showed no significant correlation with TfR density. In a patint with RARS, there was no difference in TfR density between ringed and non-ringed sideroblasts. By contrast, in a patient with AL, the TfR density of EBLs with morphological changes in nucleus was lower than that of normal EBLs. These findings suggest that the regulation mechanism of TfR in MDS was similar to normal subjects in cell maturation, hemogulobin concentration and SIGs, leaving the question why EBLs in MDS contain numerous SIGs in future. 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 クエン酸鉄投与及び純酸素負荷マウスのグアニジノ化合物の変動に関する研究 1023 1032 EN Seigo Watanabe The guanidino compounds in various mouse organs after i.p. administration of ferric citrate(Fe) and after inhalation of pure oxygen(O(2)) were studied. Guanidinoacetic acid and N-acetylarginine levels were markedly higher in the kidney, and they decreased after administration of Fe or inhalation of O(2). Creatinine decreased in the liver after administration of Fe, and it decreased in the liver and muscle after inhalation of O(2). γ-Guanidinobutyric acid level was significantly higher in the normal liver, but decreased after administration of Fe or inhalation of O(2). Arginine(Arg) increased in the kidney and muscle after administration of Fe, while it decreased in the liver. Arg decreased in the kidney and the muscle after inhalation of O(2). Methylguanidine(MG) increased in the brain after administration of Fe or inhalation of O(2). However, MG decreased in the liver after administration of Fe, and also decreased in the liver, kidney and muscle after inhalation of O(2). MG increased only in the brain. This finding suggested that the reactive oxygen species(O(2)(-), H(2)O(2), ・OH) were most effective there, because oxygen consumpution in the brain was much more than in the other organs. 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 ヒト子宮頸部組織における細胞質分画エストロゲン結合能とそれに影響する因子について 137 144 EN Shunzo Kobayashi The estrogen binding activity in the human uterine cervix was measured, and the effect of natural and synthesized steroids on the activities was determined. To assay the estrogen binding activity, the asmple was incubated with 10nM [(3)H] estradiol-17β at 30℃ for 2 hours. Then dextran-coated charcoal (DCC) was added to a final concentration of 0.5% to separate bound/free (B/F) estradiol. Estrogen binding activity was determined by subtracting the activity found in the heated sample from the corresponding activity in the untreated sample. For this purpose it was found appropriate to heat the sample at 40℃ for 60 minutes. The dissociation constant obtained from the Scatchard plot analysis was : kd=2.0×10(-9)M. A variety of steroids at the same molar concentration (1.0 μM) were added to the sample to determine their effects on the estrogen binding activity. For binding with [(3)H] estradiol-17β, the synthetic estrogens were strongly inhibitory, the anti-estrogen agents were strong-ly to moderately inhibitory. Dannazol, which has been used for the treatment of en-dometriosis, was found to be as effective as androgens. All of those inhibitory effects occur-red in a non-competitive manner. 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 セボフルレン麻酔の肝に及ぼす影響に関する実験的研究 841 857 EN Naoki Okada The hepatic effects of sevoflurane administered under different inspiratory oxygen concentrations were examined. Male rats pretreated with phenobarbital for 5 days and fasted for 24 hours were anesthetized with 2.4% sevoflurane administered under different oxygen concentrations (10%, 14%, 21% or 100%). The rats administered sevoflurane under 21% oxygen were used as the control. The amount of microsomal protein, the content and activity of hepatic microsomal enzymes, and the amount of enzymes released from the liver cells (GPT, OCT) of each group of rats were measured for 7 days after these procedures. The content of cytochrome P-450 and the activity of aminopyrine demethylation and aniline dehydration were decreased significantly to about 58%, 43% and 40% that of the control, respectively. Furthermore the plasma level of GPT and OCT was elevated to 1,107±620 IU/L and 422±270 IU/L respectively soon after sevoflurane anesthesia only in the group of rats administered sevoflurane under a 10% oxygen concentration. In this study, severe damage to the liver of the rats was observed after sevoflurane anesthesia under 10% oxygen following enzyme induction and fasting. 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 Biological response modifier としての Tumor necrosis fator の効果に対する Immunosuppressive substance の作用の検討 75 82 EN Yoshimasa Yasui TNF is a cytokine with the activity of a BRM (biological response modifier). TNF-α and TNF-β enhanced NK activity of peripheral blood mononucleocytes of a normal donor, but not in a cancer patient. ISS, a glocoprotein extracted from the ascitic fluid of a colon cancer patient with immunosuppressive properties, ia also detected in large quantities in the serum of cancer patients. NK activity of a normal donor which was in an immunosuppressive state by the administration of ISS was not affected by treatment of TNF-α or TNF-β, but the suppressed NK activity was improved by the combination of TNF with IFN-α or IFN-γ. On the other hand, NK activity of a cancer patient treated with anti-IS antiserum which was obtained from serum of rabbit immunized by ISS was enhanced by both TNFs. These findings suggest that ISS suppresses the effect of TNFs on NK activity. Furthermore, the effect of TNF as a BRM is inhibited in cancer patients due to the high dose of ISS in the serum, and that the combination of TNF with other cytokines, such as IFN, is more effective than the single use of TNF, clinically. 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 鉄欠乏性貧血の発症要因に関する研究　第2編　鉄漏出性貧血の動物モデル作製の試みとその評価 813 821 EN Norihiko Nakanishi Iron deficiency anemia results from various factors, such as blood loss, malabsorption, and increased demand for iron due to pregnancy or growth. However, iron hyper-excretion has not been reported except in the cases of bleeding. Previously, we found increased iron excretion in the urine in patients with iron-losing anemia, such as idiopathic hypochromic anemia. To examine the relationship between iron excretion and anemia, puromycin aminonucleoside (PA) was administered in rats to induce anemia. In such rats, considerable amounts of iron were continuously excreted in the urine and the animals became anemic. However, the anemia in this model was normocytic and normochromic, and the liver iron content was reversely increased. In conclusion, PA administration in rats induces not only iron deficiency as hyper-excretion but also abnormalities of iron metabolism as indicated by the other pathological findings, such as inflammatory change and renal failure. 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 鉄欠乏性貧血の発症要因に関する研究　第1編　尿中鉄排泄の臨床的並びに実験的検討 803 811 EN Norihiko Nakanishi In the "iron excretion test" , urinary iron excretion after injection of saccharated iron oxide has been reported to be accelerated in relapsing idiopathic iron deficiency anemia. To determine the relevance of urinary iron excretion to clinical factors other than iron metabolism, 15 clinical parameters were evaluated. The serum creatinine level was positively and the serum albumin level was negatively correlated with urinary iron excretion, showing coefficients of r＝0.97,－0.86 respectively, and suggesting a relationship between urinary iron excretion and subclinical abnormalities of kidney function. In experimental studies, the relation of urinary iron excretion to the renal function was examined by administration of iron in various forms to rats. Only saccharated iron oxide was excreted; chondroitin sulfate Fe, Tf-Fe and ferric chloride were not excreted in the urine. Then, iron excretion was examined in iron deficient, iron overloaded and puromycin aminonucleoside (PA)-treated animals. Iron deficient rats did not show any change in urinary iron excretion compared to the controls. Urinary iron excretion was increased in iron overloaded rats, and was further increased in the PA-treated group. These findings suggest that the subclinical abnormality in kidney function leads to the increased urinary iron excretion as a possible factor in the pathogenesis of relapsisg iron deficiency. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 7-8 1992 虚血性脳浮腫に及ぼすロイコトリエンの影響 821 832 EN Noriko Takasugi Arachidonic acid metabolites are postulated to play a role in the pathogenesis of cerebral ischemia. To examine the development of lipoxygenase metabolites of arachidonic acid in cerebral ischemia, we measured the concentration of leukotriene C4 in the gerbil forebrain following ischemia, and pretreated several animals with cyclooxygenase and lipoxygenase inhibitors. The leukotriene C4 concentration was significantly increased 1 hour after transient ischemia and cerebral edema. The incerase in the concentration of leukotriene metabolites was significantly suppressed by preteratment with the lipoxygenase inhibitors except for the cyclooxygenase inhibitor and phospholipase A2 inhibitor. Intracerebral cerebral injection of leukotriene C4 produced local intracerebral edema. Cycloxygenase inhibition may result in increased substrate availability for the lipoxygenase system. Studies of such an interaction help elucidate the pharmacological modification of detrimental vascular changes after transient cerebral ischemia. 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 気管支喘息における好酸球動態の調節に関する研究　第2編　喘息患者末梢血好酸球の遊走能に関する検討 791 801 EN Hisaho Takahashi Eosinophil infiltration in lung tissue is one of the characteristic features of bronchial asthma. Such cell infiltration seems to be induced by the eosinophil chemotactic factor (ECF). PAF and IL-5 are potent chemoattractants and activators for eosinophils. To evaluate the reactivity of eosinophils in asthmatics under various conditions, the migratory function of eosinophils to PAF and IL-5 was investigated by the modified Boyden chamber method. Eosinophils of asthmatics were highly purified using a flow cytometric method previously reported. The migratory response of the eosinophils of asthmatics was greater than that of healthy suljects. Eosinophils from atopic asthmatics showed a higher response to PAF than those from non-atopic asthmatics. Eosinophils in the attack stage showed a higher response than those in the non-attack stage. Hypodense eosinophils showed an increased migratory response. The migratory response was correlated to the serum concentration of ECP and blood eosinophil count. These findings suggest that the reactivity of eosinophils is heterogenous and relates to the degree of eosinophilia, and that IL-5 as well as PAF plays an important role in the pathogenesis of bronchial asthma. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 7-8 1992 難治性喘息における好中球の役割に関する研究　第1編　好中球からの Leukotrienes 産生能及び superoxide 産生能に関する検討 763 775 EN Ikki Shimizu The role of neutrophils migrated in the sputum and bronchoalveolar lavage fluid of intractable asthmatics is not difficult to understand. The production of leukotrienes (LTs) and superoxide stimulated by the calcium ionophores (CaI) from neutrophil-rich fraction of 29 intractable, 70 non-intractable asthmatics and 18 healthy subjects was examined by high performance liquid chromatography and a cytochrome C reduction method. Significantly larger amounts of LTC(4) and LTB(4) were produced by CaI in the neutrophil-rich fraction from asthematics, than in that from the healthy subjects (p<0.01). Moreover, a significantly larger amounts of LTC(4) was producted in the fraction obtained from the intractable asthmatics than in that from the non-intractable asthmatics (p<0.05). However, there was no significant difference in LTB(4) production between the two groups of asthmatics. The production of superoxide by concanavalin A was significantly increased in the neutrophil-rich fraction from prednisolone-within-10mg-dependent asthmatics than in those from prednisolone-over-10mg-dependent patients (p<0.01). There were correlations between the LTC(4) and LTB(4) production, and also between LTB(4) and superoxide production. LTs and superoxide released from inflammatory cells, especially neutrophils, may play an important role in the pathgenesis of intractable asthma. 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 気管支喘息における好酸球動態の調節に関する研究　第1編　喘息患者末梢血単核球由来の好酸球遊走因子（ECF）の解析 779 789 EN Hisaho Takahashi Eosinophilic infiltration in bronchial tissue is characteristic in the pathogenesis of bronchial asthma. The eosinophil chemotactic factor (ECF) derived from mononuclear cells has been reported to have some effect on the cell infiltration, and interleukin-5 (IL-5), a lymphokine derived from T lymphocytes, to be a factor related to growth, chemotaxis and activation for eosinophils. Lymphocytes accumulated in the bronchoalveolar lavage fluids of non-atopic and severe asthmatics have been shown to be highly responsive to Candida antigen, and high ECF production was observed in non-atopic and severe asthmatics by measurement of ECF activity in the supernatant of peripheral blood mononuclear cells cultured with Candida antigen. In this report, the molecular weight by gel filtration and inhibition test using anti-murine IL-5 antibody were studied to characterize the lymphocyte-derived ECF. Gel filtration analysis of the ECF indicated a molecular weight of 20,000 to 65,000 Da with a peak of activity around 40,000 to 50,000 Da. The ECF activity was reduced by incubation with anti-murine IL-5 antibody, which suggests that the supernatant contains IL-5. ECF from mononuclear cells, containing IL-5, may play an important role in the pathogenesis of eosinophil infiltration in non-atopic and severe asthmatics. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 7-8 1992 難治性喘息の病態と治療に関する研究　第2編　難治性喘息における細胞反応型アレルギーに対する選択的 Thromboxane A(2) 合成酵素阻害剤の抑制機序について 735 746 EN Arihiko Kanehiro The specific thromboxane A(2) (TXA(2)) synthetase inhibitor (OKY-046) seems to be a useful drug in the treatment of intractable asthmatics. In this study, to clarify the action mechanism of OKY-046 and the relationship between TXA(2) and prostaglandin E(2) (PGE(2)) in cell-mediated allergy, the effect of the TXA(2) receptor antagonist (AA-2414), TXA2 analogue (STA(2)) and PGE(2) for peripheral blood mononuclear cells in adult intractable asthmatics was studied. OKY-046 significantly suppressed TXB(2) production and increased PGE(2) production from the peripheral blood mononuclear cells stimulated by PHA and Candida antigen, but AA-2414 had no effect. AA-2414 suppressed lymphocyte blastgenesis, but did not suppress significantly interleukin-2 (IL-2) or neutrophil chemotactic factor (NCF) production. Furthermore, STA(2) increased lymphocyte blastgenesis stimulated by Candida antigen partially, but not dose-dependently. On the other hand, PGE(2) suppressed significantly lymphocyte blastgenesis and IL-2 and NCF production in a dose-dependent manner. These findings suggest that the action mechanism of OKY-046 is a suppressive effect of cell-mediated allergy, and that TXA(2) and PGE(2) play an important role in the mechanism of intractable asthma. 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 無機フッ素の腎に及ぼす影響に関する実験的研究 629 639 EN Atsuya Yamamoto It was previously reported that the elevation of inorganic fluorine level in plasma after inkalation of methoxyflurane causes acute renal failure. This study investigated whether the peak concentration or the duration of the inorganic fluorine is responsible for the real failure. Continuous infusion (5 millimols/liter and 10 millimols/liter) or a single intravenous bolus injection (720 millimols/liter) of sodium fluoride solution was adminstered to rabbits. The plasma concentration and the duration of the plasma fluorine was measured. There were no signs of pathological or biochemical changes that suggested renal failure when the peak plasma concentration was less than 50 millimols/liter for over 4 hours (5 millimols/liter, 24 hours), or whether peak concentration of plasma inorganic fliorine was over 50 millimols/liter for less than 4 hours (720 millimols/liter, intravenous bolus). However when 10 millimols/liter of sodium fluoride solution was administered at a speed of 10 milliliters/hour for 24 hours, the rabbits showed a peak plasma inorganic fluorine concentration over 50 micromols/liter for more than 4 hours and signs of renal failure developed ata plasma concentration of 65.8 micromols/liter 24 hours after the beginning of infusion. renal failure was mainly inthe form of edema of the tubular cells in both the cortex and medulla and abnormal biochemical changes (blood urea nitrogen 55.8±12.5 milligrams/deciliter, plasma creatinine 1.2±0.1 milligrams/deciliter). Inorganic fluorine can cause renal changes when its paek plasma concentration reaches more than 50 micromols/liter and lasts for more than 4 hours. 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 カイニン酸誘発けいれんにおける細胞外ドパミン量の経時的変化―脳内微小透析法を用いた実験的研究― 769 778 EN Masaru Ohnishi To investigate the role of brain dopaminergic systems in epilepsy, striatal extracellular levels of dopamins (DA) and its metabolites (3,4-dihydroxyphenylacetic acid : DOPAC and homovanillic acid : HVA) were measured during kainate-induced limbic seizures in freely-moving rats, using brain microdialysis. DA and its metabolites were measured by high performance liquid chromatography. Systemic injection of kainate (10mg/㎏, i. p.), which caused stable limbic seizures, significantly decreased the levels of DA and its metabolites. Intrahippocampal injection of kainae (2.5nmol), which also caused limbic seizures, significantly decreased only the DA levels, while DOPAC and HVA levels were unchanged. Similar to the results of the systemic injectjon, intrastriatal perfusion of kainate (10(-2) or 10(-6) M) significantly decreased the levels of DA, DOPAC and HVA in a dose-dependent manner. These findings indicate that, during kainate-induced limbic seizures, DA release was significantly reduced in the striatum. In conclusion, the hypofunction of striatal dopaminergic systems is related to the initiation and progress in epileptic seizures. 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 Lactobacillus plantarum におけるメリビオース代謝の高温感受性機構の解析 759 768 EN Chiyuki Tamura L. plantarum can grow on melibiose when incubated at 30℃ but not when incubated at 37℃. In this study, the temperature sensitivity of melibiose metabolism was analyzed. The melibiose metabolism seemed to consist of the melibiose transport system and hydrolyzing enzyme, α-galactosidase. α-Galactosidase was induced with melibiose at 30℃ but not at 37℃. This enzyme induced at 30℃ hydrolyzed colorimetric substrate, α-ONPG at 30℃ and 37℃. On the other hand, lactose induced α-galactosidase at both temperatures. These findings suggested that the temperature sensitivity of melibiose metabolism was not due to the induction and/or function of α-galactosidase. Thus, the effect of temperature on induction and function of the melibiose transport system was examined. Cells grown on melibiose at 30℃ exhibited the rapid uptake of [(3)H] -melibiose at 30℃ and 37℃, while [(3)H] -melibiose was not taken up by the cells grown at 37℃. The induction of the melibiose transport system seemed to be temperature-sensitive because the transport system was not inactivated by exposure of the cells to 37℃ for 3 hours. In conclusion, the temperature sensitivity of melibiose metabolism was attributed to the temperature sensitivity of the induction of melibiose transport 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 抗精神病薬によるジストニアの発現機序に関する実験的研究―σ (sigma) sites の関与について― 749 757 EN Kazuya Okumura Recent findings have suggested that neuroleptics exhibit a strong affinity for not only dopamine receptors, but also the sigma sites. Therefore, some clinical or adverse effects of neuroleptics may be due to their action on the sigma sites. This study showed that intrarubral microinjection of 1,3-di-o-tolylguanidine (DTG) or (＋) -3- (3-hydroxyphenyl) -N-1-propyl) piperidine, sigma ligands, and several neuroleptics such as haloperidol caused dystonic reactions in rats resembling tha acute dystonic reaction in humans. The intensity and duration of the dystonia induced by these drugs showed a correlation with their affinities for the sigma sites. These findings raise the possibility that the acute dystonic reaction, one of the motor side effects of neuroleptics, might be mediated via the sigma sites. On the other hand, BMY 14802, an atypical neuroleptic, never caused dystonia after intrarubral microinjection. Furthermore, BMY 14802 still inhibited the dystonia induced by intrarubral microinjection of DTG. This reduction in DTG-induced dystonia by BMY 14802 may result its direct inhibitory effects against DTG at the sites, because BMY 14802 possesses potent sigma affinty. These findings imply that sigma ligands may be divided into two categories, dystonia-reinforcing and -reducing groups. Application of this theory should lead to the elucidation of the mechanism of neuroleptics-induced dystonia and other motor side effects. No potential conflict of interest relevant to this article was reported.