Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 8 2025 A Higher Liver Fibrosis-4 Index Is Associated With More Severe Hearing Loss in Idiopathic Sudden Sensorineural Hearing Loss e89864 EN Yukihide Maeda Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryotaro Omichi Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Liver fibrosis is an important medical issue increasing over time in developed countries. Aims/objectives This study aimed to investigate whether liver fibrosis, as indicated by routine blood test parameters, influences the risk and severity of idiopathic sudden sensorineural hearing loss (ISSNHL). Material and methods Sixty-six patients with ISSNHL and 198 patients with benign parotid gland tumors (BPTs) (controls) were enrolled. Indices for liver fibrosis (Liver Fibrosis-4 index (FIB-4 index) and aspartate aminotransferase-to-platelet ratio index (APRI)) were calculated from the blood laboratory data. The pure tone average (PTA) was calculated as the mean of hearing levels at the six frequencies at the onset of ISSNHL. Severe hearing loss was defined as PTA≥60 decibels Hearing Level (dB HL). Results In risk evaluation, the FIB-4 index did not differ significantly between ISSNHL patients and controls. Regarding the severity of ISSNHL, the FIB-4 index was significantly higher in ISSNHL patients with severe hearing loss than in those with PTA<60 dB HL (P<0.05) on univariate comparison. After adjusting for age, sex, and indices of inflammation, both the FIB-4 index and APRI showed a significant association with severe hearing loss (odds ratio (OR): 5.9, 95% confidence interval (CI): 1.3-25.7, and OR: 2.2, 95% CI: 1.1-4.7). Conclusions and significance Higher liver fibrosis indices (FIB-4 index and APRI), derived from routine blood laboratory data, are associated with a more severe phenotype of ISSNHL. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0167-6903 105 4 2025 Effect of environmental conditions on seed germination and seedling growth in Cuscuta campestris 1157 1167 EN Koki Nagao Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taku Takahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ryusuke Yokoyama Graduate School of Life Sciences, Tohoku University Dodder (Cuscuta) is an obligate parasitic plant that cannot survive without a host and causes significant damage to crop yields. To understand its growth characteristics before parasitism, we examined the effects of environmental conditions on seed germination and seedling growth in Cuscuta campestris Yunck. Among various factors, we focused on the effects of light, pH, temperature, sugars, salts, hormones, amino acids and polyamines on seeds sown on agar plates. Regarding the effect of light on germination, far-red light was preferable rather than red light and the reversible response of seeds to red and far-red light was confirmed, implicating a phytochrome-mediated signaling pathway opposite to that in many seed plants. Among the amino acids, aspartic acid and alanine had a promotive effect, while histidine had an inhibitory effect on germination. We further found that, in addition to gibberellic acid, methyl jasmonate stimulated both germination and shoot elongation. While 2,4-D extended the viability of trichomes around the root cap, kinetin induced the formation of scale leaves on the shoot and undifferentiated cell clusters at the base of the shoot and root tip. Real-time reverse transcriptase PCR (RT-PCR) experiments confirmed that the expression of a putative RbcS gene for photosynthesis showed no response to light, whereas that of a Phytochrome A homolog increased in the dark. Our results indicate that some of the molecular mechanisms involved in responding to light and hormone signals are uniquely modified in dodder seedlings, providing clues for understanding the survival strategy of parasitic plants. No potential conflict of interest relevant to this article was reported.

Proceedings of the National Academy of Sciences Acta Medica Okayama 0027-8424 122 32 2025 Structural insights into a citrate transporter that mediates aluminum tolerance in barley e2501933122 EN Tran Nguyen Thao Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Namiki Mitani-Ueno Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University Ryo Urano Division of Superconducting and Functional Materials, Research Institute for Interdisciplinary Science, Okayama University Yasunori Saitoh Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Peitong Wang Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University Naoki Yamaji Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University Jian-Ren Shen Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Wataru Shinoda Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Jian Feng Ma Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University Michihiro Suga Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University HvAACT1 is a major aluminum (Al)-tolerance gene in barley, encoding a citrate transporter that belongs to the multidrug and toxic compound extrusion (MATE) family. This transporter facilitates citrate secretion from the roots, thereby detoxifying external Al ions—a major constraint of crop production on acidic soils. In this study, we present the outward-facing crystal structure of HvAACT1, providing insights into a citrate transport mechanism. The putative citrate binding site consists of three basic residues—K126 in transmembrane helix 2 (TM2), R358 in TM7, and R535 in TM12—creating substantial positive charges in the C-lobe cavity. Proton coupling for substrate transport may involve two pairs of aspartate residues in the N-lobe cavity, one of which corresponds to the essential Asp pair found in prokaryotic H+-coupled MATE transporters belonging to the DinF subfamily. Structural coupling between proton uptake in the N-lobe and citrate extrusion in the C-lobe can be enabled by an extensive, unique hydrogen-bonding network at the extracellular half of the N-lobe. Mutation-based functional analysis, structural comparisons, molecular dynamics simulation, and phylogenic analysis suggest an evolutionary link between citrate MATE transporters and the DinF MATE subfamily. Our findings provide a solid structural basis for citrate transport by HvAACT1 in barley and contribute to a broader understanding of citrate transporter structures in other plant species. 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 0910-8327 38 9 2023 Prognostic value of the liver fibrosis marker fibrosis-5 index in patients with severe isolated tricuspid regurgitation: comparison with fibrosis-4 index 1181 1189 EN Mitsutaka Nakashima 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 Machiko Tanakaya Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center Takaaki Saito Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center Yusuke Katayama Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center Satoru Sakuragi Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center Yoichi Takaya 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 The fibrosis-4 index (FIB4), a liver fibrosis maker, has been shown to be associated with the prognosis in patients with severe isolated tricuspid regurgitation (TR). Recent study showed that the fibrosis-5 index (FIB5), which was calculated by albumin, alkaline phosphatase, aspartate transaminase, alanine aminotransferase and platelet count, had better prognostic value than FIB4 in patients with heart failure. The aim of this study was to evaluate the usefulness of FIB5 index for predicting prognosis in patients with severe isolated TR and compare the prognostic value between the FIB4 and the FIB5 in those patients. This was a dual-center, retrospective study. 113 consecutive outpatients with severe isolated TR (mean age, 65.8 years; 47.8% male) were analyzed. Major adverse cardiovascular events (MACEs) were defined as the composite of cardiovascular death, hospitalization for heart failure, myocardial infarction, and stroke. During a median follow-up of 3.0 years, 41 MACEs occurred. Patients with MACEs had a lower the FIB5 than patients without MACEs. The multivariate Cox analysis revealed that the FIB5 < -4.30 was significantly associated with higher incidence of MACEs after adjusted by confounding factors. Receiver-operating characteristic curve analyses showed that prognostic values did not differ between the FIB5 and the FIB4 in whole patients and in patients aged ≥ 70 years; while, in patients aged < 70 years, the FIB5 had better prognostic value than the FIB4. The FIB5 may be a useful predictor of MACEs in patients with severe isolated TR. No potential conflict of interest relevant to this article was reported.

Japanese Society for Pediatric Endocrinology Acta Medica Okayama 0918-5739 32 4 2023 Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods 221 227 EN Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Natsuko Futagawa Department of Pediatrics, Okayama University Hospital Yuko Ago Department of Pediatrics, Okayama University Hospital Hiroyuki Miyahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Harada Department of Pediatrics, JCHO Osaka Hospital Mari Miyazawa Department of Pediatrics, Kochi Health Sciences Center Junko Yoshimoto Department of Pediatrics, Okayama University Hospital Kenji Baba Department of Pediatrics, Okayama University Hospital Tadashi Moriwake Department of Pediatrics, Iwakuni Clinical Center, National Hospital Organization Hiroyuki Tanaka Department of Pediatrics, Okayama Saiseikai General Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by pathogenic variants of cartilage oligomeric matrix protein (COMP). Clinical symptoms of PSACH are characterized by growth disturbances after the first year of life. These disturbances lead to severe short stature with short limbs, brachydactyly, scoliosis, joint laxity, joint pain since childhood, and a normal face. Epimetaphyseal dysplasia, shortened long bones, and short metacarpals and phalanges are common findings on radiological examination. Additionally, anterior tonguing of the vertebral bodies in the lateral view is an important finding in childhood because it is specific to PSACH and normalizes with age. Here, we report five Japanese patients with PSACH, with one recurrent (p.Cys351Tyr) and four novel heterozygous pathogenic COMP variants (p.Asp437Tyr, p.Asp446Gly, p.Asp507Tyr, and p.Asp518Val). These five pathogenic variants were located in the calcium-binding type 3 (T3) repeats. In four of the novel variants, the affected amino acid was aspartic acid, which is abundant in each of the eight T3 repeats. We describe the radiological findings of these five patients. We also retrospectively analyzed the sequential changes in the vertebral body and epimetaphysis of the long bones from the neonatal to infantile periods in a patient with PSACH and congenital heart disease. No potential conflict of interest relevant to this article was reported.

Cell Press Acta Medica Okayama 2589-0042 26 3 2023 Muscarinic acetylcholine receptor-dependent and NMDA receptor-dependent LTP and LTD share the common AMPAR trafficking pathway 106133 EN Tomonari Sumi Research Institute for Interdisciplinary Science, Okayama University Kouji Harada Department of Computer Science and Engineering, Toyohashi University of Technology The forebrain cholinergic system promotes higher brain function in part by signaling through the M1 muscarinic acetylcholine receptor (mAChR). Long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmis-sion in the hippocampus are also induced by mAChR. An AMPA receptor (AMPAR) trafficking model for hippocampal neurons has been proposed to simulate N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity in the early phase. In this study, we demonstrated the validity of the hypothesis that the mAChR-dependent LTP/LTD shares a common AMPAR trafficking pathway associated with NMDAR-dependent LTP/LTD. However, unlike NMDAR, Ca2+ influx into the spine cytosol occurs owing to the Ca2+ stored inside the ER and is induced via the activation of inositol 1,4,5-trisphosphate (IP3) receptors during M1 mAChR activation. Moreover, the AMPAR trafficking model implies that alterations in LTP and LTD observed in Alzheimer's disease could be attributed to age-dependent reductions in AMPAR expression levels. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2306-7381 10 3 2023 Monitoring the Milk Composition, Milk Microbiota, and Blood Metabolites of Jersey Cows throughout a Lactation Period 226 EN Peter Kiiru Gathinji Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Zabiallah Yousofi Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Karin Akada Animal Products Research Group, Institute of Livestock and Grassland Science, National Agriculture and Research Organization Ajmal Wali Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Naoki Nishino Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University This study aimed to determine how milk composition, milk microbiota, and blood metabolites may change during the lactation period in Jersey cows. Milk and jugular blood samples were collected from eight healthy cows every other month from the beginning to the end of their lactation period. Samples of airborne dust were also collected to determine whether the cowshed microbiota could affect milk microbiota. Milk yield peaked in the first two months and gradually decreased as the lactation period progressed. Milk fat, protein, and solids-not-fat contents were low in the first month, and then increased during the middle and late lactation periods. In the first month, plasma non-esterified fatty acids (NEFA), haptoglobin (Hp), and aspartate transaminase (AST) levels were elevated, and high abundances of Burkholderiaceae and Oxalobacteraceae were observed in milk and airborne dust microbiota. The finding that contamination of the environmental microbiota in milk was coupled with elevated plasma NEFA, Hp, and AST levels indicated that impaired metabolic function during the early lactation period may increase the invasion of opportunistic bacteria. This study can affirm the importance of feeding and cowshed management and should provide a helpful addition to improving Jersey cow farming. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2399-3642 5 1 2022 Structural and biochemical evidence for the emergence of a calcium-regulated actin cytoskeleton prior to eukaryogenesis 890 EN Caner Akil Research Institute for Interdisciplinary Science (RIIS), Okayama University Linh T. Tran Research Institute for Interdisciplinary Science (RIIS), Okayama University Magali Orhant-Prioux CytomorphoLab, Biosciences & Biotechnology Institute of Grenoble, Laboratoire de Physiologie Cellulaire & Végétale, Université Grenoble-Alpes/CEA/CNRS/INRA Yohendran Baskaran Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Biopolis Yosuke Senju Research Institute for Interdisciplinary Science (RIIS), Okayama University Shuichi Takeda Research Institute for Interdisciplinary Science (RIIS), Okayama University Phatcharin Chotchuang School of Biomolecular Science and Engineering (BSE), Vidyasirimedhi Institute of Science and Technology (VISTEC) Duangkamon Muengsaen School of Biomolecular Science and Engineering (BSE), Vidyasirimedhi Institute of Science and Technology (VISTEC) Albert Schulte School of Biomolecular Science and Engineering (BSE), Vidyasirimedhi Institute of Science and Technology (VISTEC) Edward Manser Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Biopolis Laurent Blanchoin CytomorphoLab, Biosciences & Biotechnology Institute of Grenoble, Laboratoire de Physiologie Cellulaire & Végétale, Université Grenoble-Alpes/CEA/CNRS/INRA Robert C. Robinson Research Institute for Interdisciplinary Science (RIIS), Okayama University Charting the emergence of eukaryotic traits is important for understanding the characteristics of organisms that contributed to eukaryogenesis. Asgard archaea and eukaryotes are the only organisms known to possess regulated actin cytoskeletons. Here, we determined that gelsolins (2DGels) from Lokiarchaeota (Loki) and Heimdallarchaeota (Heim) are capable of regulating eukaryotic actin dynamics in vitro and when expressed in eukaryotic cells. The actin filament severing and capping, and actin monomer sequestering, functionalities of 2DGels are strictly calcium controlled. We determined the X-ray structures of Heim and Loki 2DGels bound actin monomers. Each structure possesses common and distinct calcium-binding sites. Loki2DGel has an unusual WH2-like motif (LVDV) between its two gelsolin domains, in which the aspartic acid coordinates a calcium ion at the interface with actin. We conclude that the calcium-regulated actin cytoskeleton predates eukaryogenesis and emerged in the predecessors of the last common ancestor of Loki, Heim and Thorarchaeota. Calcium-regulated actin filament assembly predates eukaryogenesis and was present in the last common ancestor of Asgard archaea Loki, Heim, and Thorarchaeota. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Aging-related Characteristics of Subclinical Hypothyroidism Detected in General Practice 7 15 EN Masao Takami 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 Yasuhiro Nakano 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 Mikako Obika 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 Masanori Furukawa 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/63203 Subclinical hypothyroidism (SCH) is diagnosed when serum thyrotropin (TSH) is elevated despite a normal thyroxine level and is known to increase the risk of metabolic disorders. This study was conducted to identify potential laboratory markers suspicious for latent SCH. We retrospectively reviewed 958 outpatients in whom thyroid functions had been examined. Eighty-five (9.1%) of the 939 analyzed subjects had SCH (73% females). In the SCH group, median serum TSH and FT4 levels were 5.04 μU/ml and 1.19 ng/dl, respectively, and auto-thyroid antibodies were detected in 53.8% of patients. SCH group patients were significantly older than patients in the euthyroid group, while there was no intergroup difference in BMI. However, 56.5% of the SCH patients were asymptomatic. In the SCH group, serum aspartate aminotransferase and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher, and the estimated glomerular filtration rate (eGFR) was significantly lower than in the euthyroid group. Among patients less than 65 years of age, SCH patients tended to have lower eGFR and higher LDL-C than euthyroid patients. Age-dependent reductions of red blood cells and serum albumin were more prominent in the SCH than the euthyroid group. Biochemical changes with aging are useful as potential clues for suspecting latent SCH. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 18785352 14 3 2021 New metal complexes derived from diacetylmonoxime-n(4)antipyrinylthiosemicarbazone: Synthesis, characterization and evaluation of antitumor activity against Ehrlich solid tumors induced in mice 102993 EN Bishoy El-Aarag Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University Fathy El-Saied Department of Chemistry, Faculty of Science, Menoufia University Tarek Salem Department of Biochemistry, College of Medicine, Qassim University Nesrin Khedr Department of Chemistry, Faculty of Science, Menoufia University Shaden A.M. Khalifa Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University Hesham R. El-Seedi Department of Chemistry, Faculty of Science, Menoufia University The present study aimed to synthesize new metal complexes of diacetylmonoxime-N(4)antipyrinylthiosemicarbazone ligand and evaluate their antitumor activity. New complexes with ferric, cobalt, nickel and copper ions were prepared. Elemental, 1H Nuclear magnetic resonance, Mass spectroscopy, Electron paramagnetic resonance, Fourier Transform InfraredSpectroscopy, Ultraviolet–visible and thermal gravimetricanalysis were used to characterize the obtained complexes 1–11. An in vivo tumor model was established to investigate the effect of the naked ligand and its metal complexes 2, 5 and 8. Ehrlich ascites carcinoma solid tumor was induced in mice through subcutaneous inoculation of Ehrlich ascites carcinoma cells. The volumes of the formed solid tumors, the alanine transaminase, aspartate transaminase, albumin concentration in the serum, as well as the levels of Ki67 and p53 proteins in tumor and liver tissues were detected. All the tested complexes, especially complex 5, possessed proliferative inhibition manifested as the reduction of the tumor volume, Alanine aminotransferase & Aspartate aminotransferase activity, and the level of the Ki67 protein. Additionally, they restored the albumin concentration to normal levels as well increased the level of pro-apoptotic p53 protein. In conclusion, the antitumor activity of the newly synthesized metal complexes against Ehrlich ascites carcinoma solid tumors was proved to be mediated by the inhibition of Ki67 and induction of p53 proteins. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1759-7706 12 5 2021 Crizotinib for recurring non-small-cell lung cancer with EML4-ALK fusion genes previously treated with alectinib: A phase II trial 643 649 EN Daijiro Harada Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center Hideko Isozaki Department of Clinical Pharmaceutics, Okayama University Hospital Toshiyuki Kozuki Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center Toshihide Yokoyama Department of Respiratory Medicine, Kurashiki Central Hospital Hiroshige Yoshioka Department of Respiratory Medicine, Kurashiki Central Hospital Akihiro Bessho Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Shinobu Hosokawa Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Ichiro Takata Department of Internal Medicine, Fukuyama City Hospital Nagio Takigawa Katsuyuki Hotta Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Okayama Lung Cancer Study Group Background The efficacy of crizotinib treatment for recurring EML4‐ALK‐positive non‐small cell lung cancer (NSCLC) previously treated with alectinib is unclear. Based on our preclinical findings regarding hepatocyte growth factor/mesenchymal epithelial transition (MET) pathway activation as a potential mechanism of acquired resistance to alectinib, we conducted a phase II trial of the anaplastic lymphoma kinase/MET inhibitor, crizotinib, in patients with alectinib‐refractory, EML4‐ALK‐positive NSCLC. Methods Patients with ALK‐rearranged tumors treated with alectinib immediately before enrolling in the trial received crizotinib monotherapy. The objective response rate was the primary outcome of interest. Results Nine (100%) patients achieved a partial response with alectinib therapy with a median treatment duration of 6.7 months. Crizotinib was administered with a median treatment interval of 50 (range, 20–433) days. The overall response rate was 33.3% (90% confidence interval [CI]: 9.8–65.5 and 95% CI: 7.5–70.1), which did not reach the predefined criteria of 50%. Two (22%) patients who achieved a partial response had brain metastases at baseline. Progression‐free survival (median, 2.2 months) was not affected by the duration of treatment with alectinib. The median survival time was 24.1 months. The most common adverse events were an increased aspartate transaminase/alanine transaminase (AST/ALT) ratio (44%) and appetite loss (33%); one patient developed transient grade 4 AST/ALT elevation, resulting in treatment discontinuation. Other adverse events were consistent with those previously reported; no treatment‐related deaths occurred. Conclusions Although the desired response rate was not achieved, crizotinib monotherapy following treatment with alectinib showed efficacy alongside previously described adverse events. No potential conflict of interest relevant to this article was reported.

Nature Acta Medica Okayama 2045-2322 10 1 2020 Mechanism underlying hippocampal long-term potentiation and depression based on competition between endocytosis and exocytosis of AMPA receptors 14711 EN Tomonari Sumi Research Institute for Interdisciplinary Science, Okayama University Kouji Harada Department of Computer Science and Engineering, Toyohashi University of Technology N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) and long-term depression (LTD) of signal transmission form neural circuits and thus are thought to underlie learning and memory. These mechanisms are mediated by AMPA receptor (AMPAR) trafficking in postsynaptic neurons. However, the regulatory mechanism of bidirectional plasticity at excitatory synapses remains unclear. We present a network model of AMPAR trafficking for adult hippocampal pyramidal neurons, which reproduces both LTP and LTD. We show that the induction of both LTP and LTD is regulated by the competition between exocytosis and endocytosis of AMPARs, which are mediated by the calcium-sensors synaptotagmin 1/7 (Syt1/7) and protein interacting with C-kinase 1 (PICK1), respectively. Our result indicates that recycling endosomes containing AMPAR are always ready for Syt1/7-dependent exocytosis of AMPAR at peri-synaptic/synaptic membranes. This is because molecular motor myosin V-b constitutively transports the recycling endosome toward the membrane in a Ca2+-independent manner. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Immobility-reducing Effects of Ketamine during the Forced Swim Test on 5-HT1A Receptor Activity in the Medial Prefrontal Cortex in an Intractable Depression Model 301 306 EN Kei Takahashi Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Kitamura Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ushio 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/60368 Ketamine has been clinically proven to ameliorate depression, including treatment-resistant depression. The detailed mechanism of action of ketamine in treatment-resistant depression remains unclear. We examined the effects of ketamine on the immobility times of adrenocorticotropic hormone (ACTH)-treated rats during the forced swim test, and we explored the mechanism by which ketamine acts in this model. We investigated the neuroanatomical site of action by microinjecting ketamine into the medial prefrontal cortex of rats. A significant reduction of the rats’ immobility during the forced swim test was observed after the intraperitoneal injection of ketamine in both saline- and ACTH-treated rats. The microinjection of ketamine into the medial prefrontal cortex also decreased immobility during the forced swim test in both saline- and ACTH-treated rats. The immobility-decreasing effect of intraperitoneally injected ketamine was blocked by administering WAY100635, a 5-HT1A receptor antagonist, into the medial prefrontal cortex. These findings contribute to the evidence that ketamine can be useful against treatment-resistant depressive conditions. The immobility-reducing effects of ketamine might be mediated by 5-HT1A receptor activity in the medial prefrontal cortex. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0914-7187 34 2020 Improvement of biodistribution profile of a radiogallium-labeled, αvβ6 integrin-targeting peptide probe by incorporation of negatively charged amino acids 575 582 EN Shunsuke Nakamura Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Aya Matsuno Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masashi Ueda Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Objective Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Since αvβ6 integrin has been reported as a promising target for PDAC diagnosis, we previously developed H-Cys(mal-NOTA-67Ga)-(Gly)6-A20FMDV2-NH2 ([67Ga]CG6) as an αvβ6 integrin-targeting probe. Although [67Ga]CG6 specifically binds to αvβ6 integrin-positive xenografts, the uptake of [67Ga]CG6 in the organs surrounding the pancreas, such as the liver and spleen, was comparable to that in the αvβ6 integrin-positive xenografts. We hypothesized that the undesirable accumulation of [67Ga]CG6 in those organs was caused by the positive charges of [67Ga]CG6 (+ 3). In this study, we aimed to decrease [67Ga]CG6 uptake in the liver and spleen by reducing the electric charges of the probe. Methods We synthesized H-Cys(mal-NOTA-67Ga)-(Asp)6-A20FMDV2-NH2 ([67Ga]CD6) and evaluated its affinity to αvβ6 integrin via in vitro competitive binding assay. Isoelectric points of the probes were determined by electrophoresis. Biodistribution study, autoradiography, and immunostaining for β6 integrin were conducted using αvβ6 integrin-positive and negative tumor-bearing mice. Results In vitro competitive binding assay showed that the alteration of the linker had a negligible impact on the affinity of [67Ga]CG6 to αvβ6 integrin. The results of electrophoresis revealed that [67Ga]CG6 was positively charged whereas [67Ga]CD6 was negatively charged. In the biodistribution study, the uptake of [67Ga]CD6 in the αvβ6 integrin-positive xenografts was significantly higher than that in the αvβ6 integrin-negative ones at 60 and 120 min. The uptake of [67Ga]CD6 in the liver and spleen was more than two-fold lower than that of [67Ga]CG6 at both time points. In the immunohistochemistry study, the radioactivity accumulated areas in the autoradiogram of the αvβ6 integrin-positive xenograft roughly coincided with β6 integrin-expressing areas. Conclusion We have successfully reduced the nonspecific uptake in the liver and spleen by altering the linker amino acid from G6 to D6. [67Ga]CD6 overcame the drawbacks of [67Ga]CG6 in its biodistribution. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1420-3049 24 18 2019 Synthesis, Characterization, and In Vivo Anti-Cancer Activity of New Metal Complexes Derived from Isatin-N(4)antipyrinethiosemicarbazone Ligand Against Ehrlich Ascites Carcinoma Cells EN Fathy El-Saied Department of Chemistry, Faculty of Science, Menoufia University Bishoy El-Aarag Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University Tarek Salem Department of Molecular Biology, Genetic Engineering & Biotechnology Institute, University of Sadat City Ghada Said Department of Chemistry, Faculty of Science, Menoufia University Shaden A. M. Khalifa Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University Hesham R. El-Seedi Department of Chemistry, Faculty of Science, Menoufia University The current study aimed to synthesize new metal coordination complexes with potential biomedical applications. Metal complexes were prepared via the reaction of isatin-N(4)anti- pyrinethiosemicarbazone ligand 1 with Cu(II), Ni(II), Co(II), Zn(II), and Fe(III) ions. The obtained metal complexes 2–12 were characterized using elemental, spectral (1H-NMR, EPR, Mass, IR, UV-Vis) and thermal (TGA) techniques, as well as magnetic moment and molar conductance measurements. In addition, their geometries were studied using EPR and UV–Vis spectroscopy. To evaluate the in vivo anti-cancer activities of these complexes, the ligand 1 and its metal complexes 2, 7 and 9 were tested against solid tumors. The solid tumors were induced by subcutaneous (SC) injection of Ehrlich ascites carcinoma (EAC) cells in mice. The impact of the selected complexes on the reduction of tumor volume was determined. Also, the expression levels of vascular endothelial growth factor (VEGF) and cysteine aspartyl-specific protease-7 (caspase-7) in tumor and liver tissues of mice bearing EAC tumor were determined. Moreover, their effects on alanine transaminase (ALT), aspartate transaminase (AST), albumin, and glucose levels were measured. The results revealed that the tested compounds, especially complex 9, reduced tumor volume, inhibited the expression of VEGF, and induced the expression of caspase-7. Additionally, they restored the levels of ALT, AST, albumin, and glucose close to their normal levels. Taken together, our newly synthesized metal complexes are promising anti-cancer agents against solid tumors induced by EAC cells as supported by the inhibition of VEGF and induction of caspase-7. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 20 20 2019 Protective Effects of Flavone from Tamarix aphylla against CCl4-Induced Liver Injury in Mice Mediated by Suppression of Oxidative Stress, Apoptosis and Angiogenesis EN Bishoy El-Aarag Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University Asmaa Khairy Chemistry Department, Faculty of Science, Menoufia University Shaden A. M. Khalifa Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University Hesham R. El-Seedi Chemistry Department, Faculty of Science, Menoufia University The current study aimed to investigate, for the first time, the beneficial effects of 3,5-dihydroxy-4′,7-dimethoxyflavone isolated from Tamarix aphylla L. against liver injury in mice. Liver injury was induced by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl4) at a dose of 0.4 mL/kg mixed in olive oil at ratio (1:4) twice a week for 6 consecutive weeks. The administration of CCl4 caused significant histopathological changes in liver tissues while the pre-treatment with the flavone at dose of 10 and 25 mg/kg ameliorated the observed liver damages. Also, it markedly reduced hepatic malondialdehyde (MDA) level as well as increased the activities of liver superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) compared with their recorded levels in CCl4 model group. Moreover, the immunohistochemical analysis demonstrated the enhancement in the protein level of B-cell lymphoma-2 (Bcl-2) while the protein levels of cysteine-aspartic acid protease-3 (caspase-3), Bcl-2-associated x protein (Bax), transforming growth factor-β1 (TGF-β1) and CD31 were suppressed following the flavone treatement. These results suggest that the flavone can inhibit liver injury induced in mice owning to its impact on the oxidation, apoptotic and angiogenesis mechanisms. Further pharmacological investigations are essential to determine the effectiveness of the flavone in human. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1536-1632 21 3 2018 Evaluation of the Relationship Between Cognitive Impairment, Glycometabolism, and Nicotinic Acetylcholine Receptor Deficits in a Mouse Model of Alzheimer's Disease 519 528 EN Yuki Matsuura Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masashi Ueda Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yusuke Higaki Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Sano Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University Hideo Saji Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University Shuichi Enomoto Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University PURPOSE: In patients with Alzheimer's disease (AD), the loss of cerebral nicotinic acetylcholine receptors (nAChRs) that are implicated in higher brain functions has been reported. However, it is unclear if nAChR deficits occur in association with cognitive impairments. The purpose of this study was to assess the relationship between nAChR deficits and cognitive impairments in a mouse model of AD (APP/PS2 mice). PROCEDURES: The cognitive abilities of APP/PS2 and wild-type mice (aged 2-16 months) were evaluated using the novel object recognition test. Double-tracer autoradiography analyses with 5-[125I]iodo-A-85380 ([125I]5IA: α4β2 nAChR imaging probe) and 2-deoxy-2-[18F]fluoro-D-glucose were performed in both mice of different ages. [123I]5IA-single-photon emission tomography (SPECT) imaging was also performed in both mice at 12 months of age. Furthermore, each age cohort was investigated for changes in cognitive ability and expression levels of α7 nAChRs and N-methyl-D-aspartate receptors (NMDARs). RESULTS: No significant difference was found between the APP/PS2 and wild-type mice at 2-6 months of age in terms of novel object recognition memory; subsequently, however, APP/PS2 mice showed a clear cognitive deficit at 12 months of age. [125I]5IA accumulation decreased in the brains of 12-month-old APP/PS2 mice, i.e., at the age at which cognitive impairments were first observed; this result was supported by a reduction in the protein levels of α4 nAChRs using Western blotting. nAChR deficits could be noninvasively detected by [123I]5IA-SPECT in vivo. In contrast, no significant changes in glycometabolism, expression levels of α7 nAChRs, or NMDARs were associated with cognitive impairments in APP/PS2 mice. CONCLUSION: A decrease in cerebral α4β2 nAChR density could act as a biomarker reflecting cognitive impairments associated with AD pathology. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 07533322 117 2019 Behavioural effects of inhalation exposure to dizocilpine (MK-801) in mice 109038 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Shunsuke Suemitsu Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Naoya Kitamura Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School The complex pathophysiology of brain disorders and the difficulty of delivering therapeutic agents to the brain remain major obstacles in the research and development of new therapeutic methods for brain disorders. Therefore, delivering existing therapeutic agents to the central nervous system is expected to provide benefits in various diseases. In this study, we investigated whether inhaled central nervous system drugs reached the brain and affected mouse behaviour. Dizocilpine (MK-801), which increases locomotor activity in mice, was mainly used to study this hypothesis. First, we administered MK-801, an N-methyl-d-aspartate receptor antagonist, to mice via inhalation and examined whether it induced excessive activity similar to that observed after intraperitoneal administration. We also examined the time- and dose-dependency of drug induced changes in mouse behaviour after MK-801 inhalation. Next, we investigated whether inhalation of scopolamine, pentobarbital, and imipramine also affected mouse behaviour. Mice that inhaled MK-801 showed MK-801–induced hyperactivity similar to that observed following intraperitoneal administration. Furthermore, the extent of activity changed in a time- and dose-dependent manner after MK-801 inhalation. Inhalation of pentobarbital, scopolamine, and imipramine also changed mouse behaviour. These results demonstrate that inhalation of MK-801 exerts effects similar to those achieved with intraperitoneal and oral administration in mice. Thus, central nervous system agonists can reach the brain efficiently via inhalation. This finding may facilitate the development of improved therapies for brain disorders. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 3 2019 Anti-N-Methyl-D-Aspartate Receptor Encephalitis in Psychiatry 189 195 EN Shinji Sakamoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Okahisa Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ko Tsutsui Department of Neuropsychiatry, Akita University Graduate School of Medicine Takashi Kanbayashi Department of Neuropsychiatry, Akita University Graduate School of Medicine Keiko Tanaka Department of Animal Model Development, Brain Research Institute, Niigata University Yutaka Mizuki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihito Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/56860 Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently-discovered autoimmune disorder in which antibodies target NMDAR in the brain. The number of reported cases of anti-NMDAR encephalitis has increased rapidly. Anti-NMDAR encephalitis can be mistakenly diagnosed as psychiatric disorders because many patients present with prominent psychiatric symptoms and visit psychiatric institutions first. Thus, psychiatrists should cultivate a better understanding of anti-NMDAR encephalitis. In this review, we present the mechanisms, epidemiology, symptoms and clinical course, diagnostic tests, treatment and outcomes of patients with anti-NMDAR encephalitis. Furthermore, we discuss the diversity of clinical spectra of anti-NMDAR encephalitis, and demonstrate a differential diagnosis of psychiatric disease from the perspective of psychiatry. No potential conflict of interest relevant to this article was reported.

Nature Publishing Group Acta Medica Okayama 2045-2322 5 2015 Peptide-modified Substrate for Modulating Gland Tissue Growth and Morphology In Vitro 11468 EN Hiroaki Taketa Ara Sathi Gulsan Farahat Mahmoud Anisur Rahman Kazi Takayoshi Sakai Yoshiaki Hirano Takuo Kuboki Yasuhiro Torii Takuya Matsumoto In vitro fabricated biological tissue would be a valuable tool to screen newly synthesized drugs or understand the tissue development process. Several studies have attempted to fabricate biological tissue in vitro. However, controlling the growth and morphology of the fabricated tissue remains a challenge. Therefore, new techniques are required to modulate tissue growth. RGD (arginine-glycine-aspartic acid), which is an integrin-binding domain of fibronectin, has been found to enhance cell adhesion and survival; it has been used to modify substrates for in vitro cell culture studies or used as tissue engineering scaffolds. In addition, this study shows novel functions of the RGD peptide, which enhances tissue growth and modulates tissue morphology in vitro. When an isolated submandibular gland (SMG) was cultured on an RGD-modified alginate hydrogel sheet, SMG growth including bud expansion and cleft formation was dramatically enhanced. Furthermore, we prepared small RGD-modified alginate beads and placed them on the growing SMG tissue. These RGD-modified beads successfully induced cleft formation at the bead position, guiding the desired SMG morphology. Thus, this RGD-modified material might be a promising tool to modulate tissue growth and morphology in vitro for biological tissue fabrication. 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.

Acta Medica Okayama 0944-1174 48 3 2013 The impact of patatin-like phospholipase domain-containing protein 3 polymorphism on hepatocellular carcinoma prognosis 405 412 EN Yasuto Takeuchi Fusao Ikeda Yuki Moritou Hiroaki Hagihara Tetsuya Yasunaka Kenji Kuwaki Yasuhiro Miyake Hideki Ohnishi Shinichiro Nakamura Hidenori Shiraha Akinobu Takaki Yoshiaki Iwasaki Kazuhiro Nouso Kazuhide Yamamoto The single nucleotide polymorphism (SNP) rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with hepatic fat accumulation and disease progression in patients with non-alcoholic fatty liver disease and alcoholic liver disease (ALD). This study was conducted to determine whether PNPLA3 rs738409 SNPs affect development and prognosis of hepatocellular carcinoma (HCC) in patients with various liver diseases. We enrolled 638 consecutive Japanese patients newly diagnosed with HCC between 2001 and 2010: 72 patients with hepatitis B virus (HBV), 462 with hepatitis C virus (HCV), and 104 with non-B non-C (NBNC). NBNC patients exhibited large tumors of advanced TNM stages at HCC diagnosis, and had significantly poorer prognosis than HBV or HCV patients (P < 0.001 and < 0.001, respectively; log-rank test). The G/G genotype of PNPLA3 rs738409 SNP had significantly higher distribution in NBNC patients (P < 0.001) and was significantly associated with higher body mass index (BMI) and an increased aspartate aminotransferase to platelet ratio index. No significant differences were observed in survival with differences in PNPLA3 SNP genotypes among the patients, although ALD patients with the G/G genotype of PNPLA3 SNP and low BMI had significantly poorer survival than those with high BMI (P = 0.028). The G/G genotype of PNPLA3 rs738409 SNP was more frequently distributed, and associated with BMI and fibrosis among NBNC-HCC patients but not among HBV or HCV patients. These genotypes might affect HCC prognosis in ALD patients, but not in HBV, HCV, or NAFLD patients. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2045-2322 4 2014 Identification of a mammalian vesicular polyamine transporter EN Miki Hiasa Takaaki Miyaji Yuka Haruna Tomoya Takeuchi Yuika Harada Sawako Moriyama Akitsugu Yamamoto Hiroshi Omote Yoshinori Moriyama Spermine and spermidine act as neuromodulators upon binding to the extracellular site(s) of various ionotropic receptors, such as N-methyl-d-aspartate receptors. To gain access to the receptors, polyamines synthesized in neurons and astrocytes are stored in secretory vesicles and released upon depolarization. Although vesicular storage is mediated in an ATP-dependent, reserpine-sensitive fashion, the transporter responsible for this process remains unknown. SLC18B1 is the fourth member of the SLC18 transporter family, which includes vesicular monoamine transporters and vesicular acetylcholine transporter. Proteoliposomes containing purified human SLC18B1 protein actively transport spermine and spermidine by exchange of H+. SLC18B1 protein is predominantly expressed in the hippocampus and is associated with vesicles in astrocytes. SLC18B1 gene knockdown decreased both SLC18B1 protein and spermine/spermidine contents in astrocytes. These results indicated that SLC18B1 encodes a vesicular polyamine transporter (VPAT). No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0944-1174 44 9 2009 Mortality rate of patients with asymptomatic primary biliary cirrhosis diagnosed at age 55 years or older is similar to that of the general population 1000 1006 EN Junichi Kubota Fusao Ikeda Ryo Terada Haruhiko Kobashi Shin-ichi Fujioka Ryoichi Okamoto Shinsuke Baba Youichi Morimoto Masaharu Ando Yasuhiro Makino Hideaki Taniguchi Tetsuya Yasunaka Yasuhiro Miyake Yoshiaki Iwasaki Kazuhide Yamamoto Recent routine testing for liver function and anti-mitochondrial antibodies has increased the number of newly diagnosed patients with primary biliary cirrhosis (PBC). This study investigated the prognosis of asymptomatic PBC patients, focusing on age difference, to clarify its effect on the prognosis of PBC patients. The study was a systematic cohort analysis of 308 consecutive patients diagnosed with asymptomatic PBC. We compared prognosis between the elderly (55 years or older at the time of diagnosis) and the young patients (< 55 years). The mortality rate of the patients was also compared with that of an age- and gender-matched general population. The elderly patients showed a higher aspartate aminotransferase-to-platelet ratio, and lower alanine aminotransferase level than the young patients (P < 0.01 and P = 0.03, respectively). The two groups showed similar values for alkaline phosphatase and immunoglobulin M. Death in the young patients was more likely to be due to liver failure (71%), while the elderly were likely to die from other causes before the occurrence of liver failure (88%; P < 0.01), especially from malignancies (35%). The mortality rate of the elderly patients was not different from that of the age- and gender-matched general population (standardized mortality ratio, 1.1; 95% confidence interval, 0.6-1.7), although this rate was significantly higher than that of the young patients (P = 0.044). PBC often presents as more advanced disease in elderly patients than in the young. However, the mortality rate of the elderly patients is not different from that of an age- and gender-matched general population. No potential conflict of interest relevant to this article was reported.

Informa Healthcare Acta Medica Okayama 1071-5762 47 3 2013 Evaluation of urinary hydrogen peroxide as an oxidative stress biomarker in a healthy Japanese population 181 191 EN Y. Sato K. Ogino N. Sakano D. H. Wang J. Yoshida Y. Akazawa S. Kanbara K. Inoue M. Kubo H. Takahashi The usefulness of urinary hydrogen peroxide (H2O2) as an oxidative stress biomarker was evaluated in 766 healthy Japanese. The mean level of urinary concentrations of H2O2 was 5.66 +/- 8.27 mu mol/g creatinine, and was significantly higher in females than in males. Significant correlations of H2O2 were observed with age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), insulin, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and exercise habit in females. In both sexes, H2O2 showed a significant correlation with 8-OHdG. By a multiple logistic regression analysis, urinary H2O2 was positively associated with urinary 8-OHdG and TC and was inversely associated with insulin. By stratification of sex and age, the association of urinary H2O2 with TC was positive in both sexes under 50 years old and was inverse in males over 50 years old, and that with insulin was inverse in males over 50 years old and in females under 50 years old. Moreover, by stratification of sex and age, a positive association of H2O2 with exercise and an inverse association of H2O2 with alcohol consumption became clear in males under 50 years old, although there were no significant odds for H2O2 after adjustment for covariates. In conclusion, the present results suggest that urinary H2O2 is a useful biomarker for oxidative stress, showing an association with 8-OHdG, TC, and insulin independently. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 67 7-12 1955 実験的衝撃の生化学的研究第4篇正常猫脳髓の遊離アミノ酸に就いて 1389 1393 EN Takashi Nishimon The present work was carried on by means of 2 dimensional paper chromatography. ‘where phenol and lutidine-collidine were used. The following results were obtained. 1) Aspartic acid, glutamic acid, glutamine, γ-aminobntpric acid and taurine were remarkably demonstrated, glycine and alanine moderately, while serine, β-alanine, valine as well as leucine, slightly. 2) The free amino acids found in the brain are almost non-essential amino acids. 3) Certain fixed relation in quantitative ratio has been recognizable among glutamic acid, γ-aminobutyric acid and glutamine. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 68 11 1956 Rickettsiaの代謝に関する研究 2083 2092 EN Tadao Nakayama The auther tried the partial purification of rickettsiae proliferated in the embryonated egg yolk sacks, and measured the respiration of these partially purified rickettsiae by the usual manometric technique. The results are as follows: 1. By partial purification, it was possible to obtain more purified and not inactivated rickettsiae. 2. As a result of oxygen consumption measurement with Warburg manometer, glutamate, succinate and aspartate were strongly oxidized, and, at the same time, α-ketoglutarate, fumarate, malate, oxaloacetate, pyruvate and β-glycerophosphate were also oxidized pretty well. 3. All enzymic inhibitors showed some inhibition, of which most remarkable was that by monoiodoacetate. 4. The inhibitive action of various antibiotics is varied according to their concentration. However, aureomycin proved to show always very remarkable inhibition. 5. Though incomplete, Rickettsia tsutsugamushi has its proper metabolic system, and is inferred to keep its proliferation by completing its metabolic system in support or connection with living cells No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 69 12 1957 無カタラーゼ血液症患者の赤血球代謝に関する実験的研究第2編無カタラーゼ血液症患者及び健康人の赤血球酸素消費に及ぼす数種物質の影響 3037 3052 EN Kiyoaki Yoshida By examining the influences of protoporphyrin and of four kinds of metal ions, namely, those of iron, zinc, magnesium, and manganese, and the influences of glucose, lactate, glycerophosphate, acetate, pyruvate, glutamate, succinate, fumarate, malate, and aspartate, methylene blue and DPN, on the oxygen consumption of erythrocytes both in acatalasemia patients and the normal, and by further spectroscopic studies on the changes of the hemoglobin accompanying the respiration of erythrocytes when malate and aspartate of these had been used as substrates, the author reached the following conclusions: namely, in the respiration of erythrocytes of these patients as compared with the normal, no marked difference other than a comparatively weaker enzymatic action of malic dehydrogenase and the enzymes concerning aspartic acid oxidation can be recognized; and as for the disposal of small amounts of H(2)O(2) supposedly to be liberated during respiration of erythrocytes, the compensation by peroxidase, hemoglobin, or other hemin proteins may be thought to be sufficient. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 69 12 1957 無カタラーゼ血液症患者の赤血球代謝に関する実験的研究第1編無カタラーゼ血液症患者及び健康人の赤血球呼吸に伴う焦性ブドウ酸量の消長 3031 3036 EN Kiyoaki Yoshida By adding various substrates such as glucose, lactate, pyruvate, aspartate, malate, and alanine to both acatalasemia patients and the normal, the fluctuation of the pyruvic acid contents accompanying the respiration of erythrocytes had been investigated, but no difference of the contents could be observed between the two groups. Thus it has now become clear that even in these patients the pyruvic acid in erythrocytes, in so far as the respiration of erythrocytes, takes hardly any acitve part in the disposal of H(2)O(2)supposedly to be liberated during respiration. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 69 10 1957 発育電位時間曲線によるチフス菌代謝の研究第3編電位における二基質の相互作用 2631 2635 EN Kazuo Akita In the present part, the author studied the interaction of two substrates to oxidation-reduction potential. Salmonella typhi 57 S was used as the test organism. The results were as follows: 1) The combination of glucose and glutamate, markedly accelerated the fall of potential, while those of glucose and alanine, and glucose and lactate accelerated it moderately. 2) The combinations of aspartate and lactate, glutamate and lactate, malate and glutamate, alanine and malate, and aspartate and alanine did not noticeably accelerate the fall of potential. 3) In the combinations of aspartate and glucose, and lactate and alanine, contrary to the above-mentioned ones, the fall of potential was less than that in each of the substrates. 4) As the cause for the effect of the combinative administration of two substrates, transamination will play a very important role, and the opinion that the hydrogen production by hydrogenlyase is the only cause for the rapid fall of potential, can not be approved as a whole. The essential cause will be, however, disclosed by the studies in future. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 69 10 1957 発育電位時間曲線によるチフス菌代謝の研究第2編各基質における酵素促進剤及び阻害剤の電位に及ぼす影響 2615 2630 EN Kazuo Akita In the present part, the influence of various enzyme-activators and -inhibitors on oxidation-reduction potential was studied. The salt solution (pH 7.2) was used as the fundamental culture medium; Salmonella typhi 57 S as the test organism. The results were as follows: 1) In the medium of glucose or pyruvate Mg(++) of the concentration over 10(-4)M accelerated the fall of potential. 2) 10(-2)M KCN inhibited the fall of potential in the media of all the substrates tested, whereas 10(-3)M inhibited it in those of the substrates other than pyruvate, succinate, aspartate and alanine, and 10(-4) M inhibited only in that of lactate. 3) NaF of the concentrations over 10(-3) M inhibited the fall of potential in the media of the substrates other than lactate, acetate and succinate. 10(-1) M NaF, however, showed some inhibition even in that of succinate. 4) NaN(3) of all concentrations inhibited the fall of potential in the media of all the substrates other than lactate, acetate and succinate. However, 10(-1)M in the medium of lactate, 10(-3) M in that of acetate, 10(-2) M in that of succinate inhibited the fall of potential. 5) Monoiodoacetic acid of the concentrations over 10(-3) M inhibited the fall of potential in the medium of lactate, that over 10(-4) M inhibited it in that of succinate. 6) 2, 4-Dinitrophenol of all the concentrations tested inhibited the fall of potential in the media of all the substrates tested. 7) The inhibitive action of these five sorts of inhibitors to the fall of potential resembled their action to the oxygen consumption of Salmonella typhi. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 69 10 1957 発育電位時間曲線によるチフス菌代謝の研究第1編各基質における電位時間曲線の研究 2605 2613 EN Kazuo Akita In order to study some metabolic aspects of Salmonella typhi, the author measured the innert electrode potential of the culture media at 37.5 C with the lapse of time. M/50 phosphate buffer and salt solution were used as the fundamental culture media; glucose, pyruvate, lactate, succinate, malate, glutamate, aspartate and alanine as the substrates; Salmonella typhi 57 S as the test organism. The results were as follows: 1) The most remarkable fall of potential was observed in the media of 10(-3) M glucose, pyruvate and malate, and in 10(-2) M acetate and succinate 2) In the media of lactate or aspartate of the concentration from 10(-1) to 10(-4) M, the potential falled with the decrease of concentration of substrate, while, in that of glutamate, the reverse interrelation was observed. In the media of alanine, no definite interrelation was observed. 3) The lowest potential was below 0 V in the media of glutamate, aspartate and glucose; 0 +100 mV in those of pyruvate, lactate and succinate; +100 +200 mV in those of acetate; +200 +300 mV in that of alanine. 4) When glucose, acetate and glutamate were used as the substrates, the fall of potential was less in phosphate buffer than in salt solution, while, when pyruvate, lactate, succinate, malate, aspartate and alanine were used, the fall of potential was less in salt solution than in phosphate buffer. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 69 10 1957 口腔内病巣より分離したブドー球菌の性状について第1編溶血毒産生について 2485 2495 EN Ritsuya Yasui Using 4 strains considered to belong to Staphylococcus aureus and albus, selected from various bacteria isolated from the human mouth as test bacteria and one strain each of the standard-strain bacteria kept in our laboratory as the control, the author made comparative studies of the productivity of hemolysins of both growing bacteria and resting cells as well as investigated effects of various conditions on the production of hemolysins. The results are presented in the following. 1. By passage through the animal the productivity of hemolysin increases markedly in the case of standard strain of aureus while with albus the increase is only slight. 2. On the whole the productivity of hemolysin of the bacteria belonging to aureus strain is greater than those belonging to the albus, and No.2 and standard strain of aureus presents the hemolyzat the highest degree. 3. Nitrogen source is required in the production of hemolysins by resting cells, and the most effective one is pepton; while among amino acids, glutamate, aspartate, alanine and glycine are effective, but there is no amino acid known to be indispensable to the hemolysin production. Though hemolysin production does not occur when carbon source alone is added, when C-source is added in combination with N-source, the hemolysin production is enhanced. However, in the case of sugars, pH is lowered during the oxidation so there is a tendency to inhibit the hemolysin production. 4. Hemolysin production is inhibited by such metal ions as Fe(++), Mg(++), Co(++) and Cu(++), and it is likewise inhibited by monoiodoacetate, aureomycine, and chloromycetine. 5. Hemolysin produced by the resting cells are all unstable against heat with exception of standar strain of albus. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 69 5 1957 急性膵臓壊死に関する実験的研究第3編濾紙クロマトグラフイによる壊死膵内遊離アミノ酸に就いて 1299 1309 EN Mitsugu Yakushiji The method of experiment of acute pancreatic necrosis in dogs was same as the described in Chapter I. The measurement was performed by the following method. Free amino acid in the pancreatic tissue was extracted by Dent's method. Chromatography was performed by a two-dimensional method using phenol and lutidincollidine solution, and phenol and butanol-acetic acid solution. The following results were obtained. In the normal pancreatic tissue the follwing 8 free amino acids were found: cystine, aspartic acid, glutamic acid, serine, glycine, lysine, arginine and threonine. In the diseased pancreatic tissues, leucine, valine and tyrosine were found besides the above eight. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 69 3 1957 Sh. flexneriに属する菌のamino酸代謝第1篇菌の発育とamino酸代謝能の関係 611 618 EN Seishi Ushida This experiment was conducted to examine the effect of aspartate and glutamate as N source and cysteine and methionine as S source for the growth of some strains belonging to Sh. flexneri, and the ability of amino acids syntheses by the resting cells of each strain. Thus the following results were obtained. 1. These organisms generally need aspartate or glutamate as N source and cysteine or methionine as S source, and many of them require nicotinamide. It is interesting that in each strain belonging to Sh. flexneri la, 3a, when growth medium is glutamate-cysteine system the organisms require nicotinamide, but when glutamate-methionine system, they do not require it. 2. If each of amino acids, such as aspartate, glutamate, alanine, is added to resting cells suspension independently, the formation of the other kinds of amino acids is little, but if each of them is added with glucose, the formation is great. At this time formed amino acids are mostly aspartate, glutamate and alanine, but to form valine from glutamate. and glucose with a strain in Sh. flex. 2b is peculiar. The above mentioned synthetic reaction of amino acids is remarkably accelerated by the addition of cysteine and methionine. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 69 2 1957 細菌のグルタミン酸代謝に関する研究第二篇白色ブドウ球菌のグルタミン酸代謝 549 560 EN Yoshimi Akita As to the physiological or metabolic features of pathogenic staphylococci, there are only a few reports, compared with those of Escherichia coli which was treated in report I. In this report, the author reports about the physiological aspects, particularly about the terminal respiratory system of Staphylococcus albus, entering from the studies of glutamic acid metabolism: 1) Staph. albus has the so-called citric acid cycle as its terminal respiratory ststem. 2) As a result of oxidative deamination, glutamic acid enters into the citric acid cycle and is further oxidized through this cycle. Glutamic acid is, however, best oxidized of all the intermediates of citric acid cycle and the related compounds. 3) Glutamic-aspartic and glutamic-alanic transaminations are carried out by this organism, in which glutamic acid plays the central role. 4) Divalent metal ions (Mg(++), Mn(++) and Fe(++)) show no remarkable effect on the glutamate-respiration of Staph. albus. 5) Of the various inhibitors tested, sodium azide, 2: 4-dinitrophenol, sodium arsenite and 8-hydroxyquinoline inhibit the glutamate-respiration strongly, and the most remarkable is the inhibitive action of 8-hydroxyquinoline. 6) Of the various antibiotics used, the inhibitive action of aureomycin is the most remarkable. Penicillin also shows some inhibitive action at pH 5.4. 7) The inhibition of the glutamate-respiration of this organism by these various inhibitors and antibiotics shows usually the tendency to rise up in the region of lower pH. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 69 2 1957 細菌のグルタミン酸代謝に関する研究第一編大腸菌のグルタミン酸代謝とその定量分析への応用 541 547 EN Yoshimi Akita It is well known that glutamic acid, as well as aspartic acid, plays an important role in the metabolism of microorganisms. The author performed many experiments in order to study the physiological aspects of E. coli communis from the stand point of glutamic acid metabolism, and to apply it to the analysis of glutamic acid. The results were as follows: 1) E. coli can grow at any pH within the range from 5.4 to 8.0, but the growth is the best at pH 6.8 to 7.0. 2) The more remote from the optimum the cultural pH is, the nearer it comes to the optimum after the growth. This phenomenon is particularly remarkable on the acid side. 3) Using glutamic acid as substrate, the decarboxylation is chiefly carried out on the acid side, the deamination on the neutral or slightly alkaline side, and these two reactions are carried out simultaneously at pH 5.5 to 6.5. As for the optimum pH, pH 5.0 for decarboxylation and 7.0 for deamination. 4) The lower the cultural pH is, the higher the glutamic decarboxylase activity of the cultured organism becomes. The optimum reaction pH is, however, never shifted. 5) The E. coli, which was cultured in the pyridoxin-containing semi-synthetic medium, shows a very high activity to glutamic acid, but not to α-ketoglutaric acid, aspartic acid, alanine and pyruvic acid. 6) The aceton powder of the E. coli, which was cultured in the pyridoxin-containing semi-synthetic medium, still has the high glutamic decaboxylase activity. The optimum pH is from 4.4 to 5.1, where carbon dioxide is evolved quantitatively. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 12-1 1959 コレラ菌のアミノ酸代謝について第1篇発育に於けるN源, C源の影響第2篇静止菌のアミノ酸代謝 8003 8016 EN Yasuo Nakao Part I Effet of N and C-sources on Growth, of Vibrio Cholera Using the 3 strains of Vibrio cholera as test organisms, the original strain (INABA's strain), the intermediate variant strain (HIKOZIMA's strain) and the variant strain (OGAWA's strain), the author studied the effect of N- and C-sources on growth of these microorganisms, and obtained the following results. 1) The intermediate variant strain could be cultured by serial transfers on the madia containing glutamate as N-source and did not need other C-source or vitamins for its growth. While the other 2 strains, the original and the variant strains, could not be cultred successfully without the addition of yest extract into the media. Also these 2 strains could be cultured by serial transfers on the media containing peptone or casein hydrolysate instead of yeast extract, but failed to grow on the madia containing some dozen species of amino acids. 2) An acceleration effect on growth of the microorganisms was not so remarkable as in the case of other bacteria by the addition of C-sources except lactate. Although the addition of lactate showed the acceleration effect fairly well, contrarily that of glucose acted rather inhibitory on the growth. This evidence was possibly arisen from a decrease of pH of the media being caused by the oxidation of glucose. Part 2 Amino Acids Metabolism of Resting Cells Using the 3 strains of Vibrio chlera as in the preceding paper, Part I, the author studied on the oxidation and the convertion of amino acids by these microorganisms and obtained the following results. 1) All the microorganisms tested showed an accelerated O2-uptake at the expense of aspartic acid, glutamic acid, alanine and cysteine as substrate; but showed rather small O(2)-uptake at the other amino acids. 2) The optimum pH was found to be at about 7.0 on the oxidation of aspartic acid, glutamic acid and alanine. And the amino acids mentioned here were oxidized through deamination at the pH ranging 5.0 to 8.0. 3) The convertion of the amino acids from these mentioned above to the others was carried out more successfully by these microorganisms compared with the other. 4) Concerns about the fate of oysteine, it was supposed this amino acid would be undergone in the first place a deamination and a desulfhydration resulting in pyruvate. 5) Though tryptophanase activity was observed to some extent on the bacterial cells harvested from media just before test, the activity was raised adaptatively by the shaking of the resting cell suspension in the presence of tryptophane. However, this adaptation of microorganisms was inhibited with the addition of glucose. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 11-2 1959 脳のアミノ酸代謝(IX) 成熟ニワトリ脳におけるトランスアミネーション 7551 7554 EN Tatsuo Yamada As a link in the studies on the transamination in the brain the author made a series of systematic studies on the transamination reactions in the brain of growing chick embryos, chicks at various stage of their growth, using 15 α-amino acids, 4 diamino acids, cysteic acid and α-ketoglutaric acid, and reported the result of such studies in previous papers. In the present experiment the transamination in the adult chicken brain was estimated in the similar way with the use of the same amino acids as in the previous experiment. 1. Of all the amino acids that showed the transaminase activity in the chick embryo and the chick brains at every developemental stage, lysine did not shows the activity in the adult chicken brains. 2. The grade of the transaminase activity of aspartic acid, isoleucine, β-alanine and cysteic acid is lower than the peak of the same observed in the eavly stage of the chick brains. As for the other amino acids with an exception of alanine which showed the greatest activity in the adult chicken brain, none showed the activity surpassing the maximum shown in the chick brains at every developemental stage. 3. Spcaking relatively and biochemically at least in the chicken brain the transamination reactions in the chicken brains, especially to that of the mouse brain. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 11-2 1959 脳のアミノ酸代謝(VIII) 発育中のニワトリヒナ脳におけるトランスアミネーション 7547 7550 EN Tatsuo Yamada With the growing chick brains take out at 9 different times during the period immediately after hatching to 40 days later the author studied the transaminase activity in these brains. The results are follows. 1. In α-amino acids group aspartic acid, alanine, isoleucine, lencine, valine, norvaline. and tyrosine show the transaminase activity as the continuatoin from embryo and phenylalanine commences its transaminase activity. 2. In ω-amino acid group γ-aminobutylic acid, β-alanine, β-oxy-γ-aminobutylic acid, in the diamino acid group ornithine show the transaminase activity, while cysteic acid also as the continuation from the embryo shows the activity in every period examined. 3. Those amino acids showing the transaminase activity have individual peaks during the period from 4 to 10 days after hatching, and thereafter these amino acids take two different courses; namely, on that slightly falls folowing the respective Peak; and one that stays unchanged. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 11-2 1959 脳のアミノ酸代謝(VII) 発育中のニワトリ胚胎脳におけるトランスアミネーションについて 7541 7545 EN Tatsuo Yamada Using the chick-embryo brains in its various developmental stage and by means of paperchromatography. the author studied transamination of 15 different α-amino acids, 4 ω-amino acids, and α-ketoglutaric acid from embryo-chemical standpoint, and investigated the relationship between the germination, functional activity and amino acid metabolism in the growing chick embryo brains. The following are the resnlts. 1. In the early stage of chick embryo brain which begins to germinate and develope, only a minimal transaminase activity can be recognized, but on about 11th embryonic day the activity grown gradually and consistently. On the day of hatching the transaminase activity is almost the same as in a chick. 2, Aspartic acid, alanine, isolecine, leucine, valine, norvalin, tyrosine, ornithine and β-oxy-γ-amino acid, alanine, isoleuciue, leucine, valine, norvaline and cysteic acid immediately before hatching reaches about the same as found in other maturede animals such as mous (8) and dog (10). No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 10-1 1959 脳髄組織における(14)C-glucoseのアミノ酸への転化に関する研究第2編真正癲癇患者ならびに潜在性脳局所アナフィラキシー家兎の脳髄おにける(14)C-glucoseより脳遊離アミノ酸への転化について 6455 6461 EN Takaaki Kuroda The conversion of (14)C-labelled glucose to free amino acids by homogenates of brain tissues from idiopathic epleptics, non-epileptics as well as normal and LCLA rabbits was studied. 1) The turnover of (14)C-labelled glucose to free amino acids in idiopathic epileptic brain was more disturbed than that in non-epileptic brain: to asparagine and glutamine no significant differences wee seen, but especially to gluamic acid it was slightly disturbed and to aspartic acid and γ-aminobutyric acid they were intensively disturbed. In idiopathic epileptic brain no γ-aminobutyric acid was proved. 2) In one case of focal epileptic brain, the conversion of aspartic acid was more restrained in the focus than in the contrast part. 3) In LCLA rabbit brain, the turnover of free amino acids were generally more disturbed than that by normal one. To glutamine and asparagine no significant difference was found but to glutamic acid it was slightly and to γ-aminobutyric acid it was markedly disturbed. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 10-1 1959 脳髄組織における(14)C-glucoseのアミノ酸への転化に関する研究第1編人脳および家兎脳homogenateによる(14)C-glucoseよりアミノ酸への転化について 6449 6454 EN Takaaki Kuroda The conversion of (14)C-labelled glucose to free amino acids by homogenate of human and rabbit brain was studied by paper chromatgraphy and radioautography with X-ray film. Results were: 1) In both human and rabbit brain glutamine, asparagine, glutamic acid, aspartic acid and γ-aminobutyric acid with radioactivity were derived from (14)C-labelled glucose. Moreover in rabbit brain alanine was also derived. 2) In normal rabbit brain the derived amino acids were investigated. During short incubate time the precoursors such as aspartic acid and glutamic acid appeared quickly and intensively. Next asparagine and glutamine showed up and then alanine and γ-aminobutyric acid were proved. 3) It needed 24 hours for all free amino acids to appear sharply. 4) The optimal pH of this reaction was 8.5-9.0 No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 9-1 1959 脳のアミノ酸代謝に関する研究第II編脳トランスアミナーゼに関する研究 5651 5657 EN Tadao Kokudo The activities of aspartic-glutamic transaminase and γ-aminobutyric-glutamic transaminate in rabbit brain and human cerbral cortex were determined. Results were: 1) In rabbit brain with repeated convulsions caused by electro-shocks for 10 days (5 times a day), the activity of aspartic-glutamic transaminase was less than that in the normal rabbit, but the activity of γ-aminobatyric-glutamic transaminase increased. However, there were no significant differences. 2) The activities of aspartic-glutamic transaminase and γ-aminobutyric-glutamic transaminase in the cerebral cortex of epilepsia decreased as compared with non-epileptic Iatients (patients with bran tumor), however no significant differencae were found. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 9-1 1959 脳の遊離アミノ酸について(X) ニワトリ脳，活動期クサガメ脳の遊離アミノ酸およびその関連物質 5513 5517 EN Tatsuya Aoyama From the comparative biochmical standpoint the author isolated and estimated free amino acids and related substances in the brains of Hen (Gallus domesticus) and Common turtle (Geoclemys reevesii) in active stage, and obtaind the following results: 1. The free amino acid pattern of the hen brain is on the whole similar to that of the albino rat brain, containing X(3) and X(6) but no urea. 2. The free amino acid pattern of the common turtle brain reveals characteristics as the cold blooded animal and contains markedly greater volumes of aspartic acid, glutamic acid, glycine, alanine, glycerophosphoethanolamine, phosphoethanolamine and taurine as compared with those in the hibernating turtle. As for the volum of γ-amino butyric acid there can be recognized no difference between the brain of active turtle and that of hibernating one. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 8-2 1959 腦下垂体とトランスアミナーゼ活性 III 成長ホルモン及びアトニン+ACTHの正常及び脳下垂体剔出ラットの脳肝トランスアミナーゼ活性に及ぼす影響 5241 5245 EN Susumu Higashi The author estimated the effects of GH or Atonin-ACTH administration on the transaminase activity in the rat brain and liver. The activities determined were aspartate-glutamate (AsGT), alanine-glutamate (AlGT), and γ-aminobutyrate-glutamate (γAGT) transaminases. The GH administration was found noneffective on the transaminase activities of the brain and liver of the normal rat. When GH was administered to the hypophysectomized rat, the previously increased activites of the AsGH and γAGT in the brain and liver decreased to the normal values. By the administration of Atonin-ACTH, the AsGT activities of the brain and liver increased in the case of the normal rat, and decreased in the case of the hypophysectomized rat. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 8-2 1959 腦下垂体とトランスアミナーゼ活性 II ACTHの正常及び脳下垂体剔出ラツト脳肝トランスアミナーゼ活性に及ぼす影響 5237 5240 EN Susumu Higashi The author estimated the effect of ACTH administration on the transaminase activity in the rat brain and liver. The activities determined were aspartate-glutamate (AsGT), alanine-glutamate (AlGT) and γ-aminobutyrate-glutamate (γAGT) transaminases. The AsGT activities in the brain and liver of the normal rat increased by the administration of ACTH. When ACTH was administered to the hypophysectomized rat, the previously increased activities of the AsGT in the brain and liver decreased to the normal values. The ACTH administration was found noneffective on the AlGT and γAGT activities in the brain and liver of the normal and hypophysectomized rat. The author described some discussion about the difference of the effect of ACTH on the activities of the various transaminases. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 8-2 1959 腦下垂体とトランスアミナーゼ活性 I. 脳下垂体剔出のラット脳肝トランスアミナーゼ活性に及ぼす影響 5231 5235 EN Susumu Higashi The author estimated the effect of hypophysectomy on the transaminase activity in the brain and liver of the Wister albino rat. The activities determined were aspartate-glutamate (AsGT), alanine-glutamate (AlGT), and γ-aminobutyrate-glutamate (γAGT) transaminases. The activities of AsGT and γAGT increased remarkably in the brain and liver of the hypophysectomized rat. The AlGT activity of these organs did not change under the same condition. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 8-2 1959 各種可欠アミノ酸の骨髄造血機能に及ぼす影響第2編家兎骨髄組織培養に於ける偽好酸球遊走能に及ぼす各種可欠アミノ酸の影響 5079 5085 EN Bin Zen Lee By adding polytamine, by-product of cow's milk hydrolysis and 10 different non-essential amino acids as already mentioned in Part 1 directly to rabbit bone-marrow tissue culture, the author studied influences of these amino acids on the wandering velocity of mature pseudoeosinophils in the bone marrow. 1. Polytamine and by-product of cow's milk caseous hydrolysis do not at all affect the wandering velocity of pseudoeosinophils. 2. Hydroxyproline, proline and cysteine, when added in a high concentration, all accelerate the wandering velocity but they do not at all affect the wandering velocity when added in a low concentration. Moreover, cysteine has been found to accelerate the wandering velocity even 12 hours after the start of culture just as much as at the third hour. The other two accelerate the wandering velocity markedly up to the sixth hour of culture. 3. Glutamic acid accelerates the wandering velocity slightly. 4. Arginine, serine, glycine, tyrodine, aspartic acid, and ornithine have neither accelerating action nor inhibitory action on the wandering velocity of pseudoeosinophils. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 8-2 1959 各種可欠アミノ酸の骨髄造血機能に及ぼす影響第1編家兎骨髄組織培養に於ける白血球増生に及ぼす各種可欠アミノ酸の影響 5067 5078 EN Bin Zen Lee By adding such substances as polytamine, a derivative of amino acids (a by-product of caseous fermentation of cow's milk), by-product of cow's milk caseous hydrolysis with acid, and ten different non-essential amino acids contained in polytamine directly to rabbit bonemarrow tissue culture, the author estimated the tissue growth area and cell density and studied influences of these substances on the production of the leucocyte series in the bone marrow. The results are as follows. 1. Both polytamine and by-product of cow's milk caseous hydrolysis with acid can increase the growth area slightly more than the control only in a high concentration. 2. With addition of L-hydroxyproline in the concentration from 0.1 to 0.0001 per cent, this substance in any concentration within this range increases the growth area and cell density 2-3 times that of the control, showing the greatest values among amino acids used in the present experiment. 3. Both L-proline and L-arginine in high concentration increase the growth area twice the control, and slightly at low concentration. 4. L-Cysteine, L-tyrodine, and DL-serine each in a proximal concentration can only increase the growth area slightly more than the control. 5. L-Aspartic acid and L-glutamic acid, glycine, and L-ornithine show hardly any significant difference as compared with the control. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 8-1 1959 脳コリンエステラーゼにおよぼすアミノ酸の影響に関する研究第2編潜在性脳局所アナフイラキシー家兎大脳皮質のコリンエステラーゼ活性におよぼすアミノ酸の影響について 4679 4685 EN Michiya Yamaguchi Various influecnes of amino acids upon ChE activity in the brain of latent cerebral local anaphylactic rabbits (LCLA rabbits) and normal ones were studied. 1) The ChE activity in the brain of LCLA rabbits accelerated stronger than that of normal rabbits, but after adding amino acid it fell to normal value or less. 2) By addition of amino acid the ChE activity redueces both in normal rabbits and LCLA rabblts, but it was more marked in the latter. 3) The intensity of the straint of amino acids for the ChE activity is the largest by glutamine to normal rabbits. Aspartic acid, γ-aminobutyric acid, asparagine, glutamic acid follows. To LCLA rabbits glutamine effects excellent and then asparagine, γ-aminobutyric acid, aspartic acid, glutamic acid. 4) If the density of adding amino acid solution is changed in glutamine and glutamic acid, they show a maximum straint at M/10. In glutamine it shows respectable straint even at M/200. 5) The influence of glutamine upon the ChE activity in the brain of LCLA rabbits showed straint even at M/100 and at M/200 it became equal with the level of normal rabbit brain. This is found to be almost the same value as the deficient value of amino nitrogen in LCLA rabbit brain. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 8-1 1959 脳コリンエステラーゼにおよぼすアミノ酸の影響に関する研究第1編真性癲癇大脳皮質のコリンエステラーゼ活性におよぼすアミノ酸の影響について 4671 4677 EN Michiya Yamaguchi The ChE activity of cerebral cortex resected from idiopathic epileptics and non-epilcptics and the influences of glutamic acid, glutamine, aspartic acid, asparagine, γ-aminobutyric acid and γ-amino-β-hydrooxybutyric acid were studied. 1) In the brain of idiopathic epileptics, ChE activity is more markedly accelerated than that in the brain of non-epileptics. 2) By adding the amino-acids mentioned above, restraint occurs in each case. The intensity of these restraint for the non-epilcptic brain has the order of asparagine, glutamine, γ-amino-β-hydroxybutyric acid, glutamic acid, aspartic acid, glutamine. γ-aminobutyric acid, while that for idiopathic epileptic brain it is asparagine, aspartic acid, glutamine, γ-amino-β-hydroxybutyric acid, glutamic acid γ-aminobutyric acid. 3) The reduction of ChE activity by adding amino acids is found in each case of epileptic and non-epileptic brain. But it is not so definite in epileptic brain as in none-epileptic brain. 4) The ascending of ChE activity in idiopathic epileptic brain is regarded to be caused by the reduction of free amino acids in idiopathic brain. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 6-2 1959 脳の遊離アミノ酸について(X) 成熟ヒト脳およびヒト胎児脳各部位における遊離アミノ酸およびその関連物質について 3187 3191 EN Nobuhiro Fukai イオン交換クロマトグラフイーをもちいて,妊娠5ケ月および8ケ月胎児脳の各部位ならびに18才結節性硬化症患者脳の前頭葉,腫瘍周辺の非結節性組織について遊離アミノ酸およびその関連物質を各々分離定量した. 1) 妊娠5ケ月なうびに8ケ月胎児脳と成熟ヒト脳を比較すると,胎児脳と生後ヒト脳との間にはその遊離アミノ酸量にかなり著明な差異を認める. 2) 胎児脳では,脳各部位ともに多少の例外はあるが,生育の段階につれてタウリン,ホスホエタノラミン,グリシン,アラニン等は減少し,グルタミン酸,アスパラギン酸, γ-アミノ酪酸等は増加する傾向を示している. 3) γ-アミノ酪酸は胎児脳のいずれでも,視床下部で最高値を示した. 4) 生後のヒト脳で多量に測定され得るシスタチオニンは胎児脳にはほとんど存在しない. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 6-1 1959 細菌のトリプトファン代謝に関する研究第2編腸チフス菌のトリプトファン代謝 2997 3007 EN Minoru Inada It is well known that tryptophan is necessary for the growth of B. typhosus. The anthor analyzed this requirement of tryptophan from the point of view of the nutritive requirement of B. typhosus. The results were as follows: 1) Of ten strains, seven strains require tryptophan for growth, three strains do not. 2) S-58 which requires tryptophan utilizes no amino acid singlely as N source and S-60 which does not require tryptophan utilizes singlely glutamic acid, cystine and aspartic acid. Glutamic acid is especially utilized by S-60. 3) S-58 does not grow in the absence of tryptophan and grows scarcely in the absence of cystine and grows a little in the absence of aspartic acid. On the contrary S-60 grows in the presence or absence of tryptophan and grows scarcely in the absence of cystine and grows a little in fhe absence of aspartic acid. 4) Tryptophan has the effect on growth at 10(-8) Mol. From this and the fact that above mensioned the strain which requires tryptophan could not grow in the absence of tryptophan tryptophan is fouud to be “growth factor” fot the strain. 5) Indole is found to be approximately equally effective as tryptophan. 6) Indole acetic acid and skatole is more weak effective compared with indole. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 4-1 1959 脳のアミノ酸代謝(IV) ナマズ脳におけるトランスアミネーションについて 1641 1645 EN Akimasa Imai Using the brains of catfish (Parasilurus asotus) and mouse as the test materials and with the aid of paper chromatography the author compared the transamination of 16 kinds of α-amino acids, 4 different ω-amino acids, 4 di-amino acids, cysteic acid and α-ketoglutaric acid and studied the possibility of the amino acid metabolism in the brain of catfish. The results are as follows: 1. The brains of catfish demonstrate generally a high transaminase activity as compared with the brains of mice, especially the activity of aspartic acid, alanine, leucine and threonine is marked. 2. Glycine and methionine that are not transaminated in the mouse brain demonstrate their activity in the brain of catfish. 3. Phenylalanine is not transaminated in the brain of catfish. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 4-1 1959 脳の遊離アミノ酸について(IX) 下垂体剔除の脳遊離アミノ酸およびその関連物質におよぼす影響 1635 1639 EN Hirosuke Nishioka With the aid of the chromatography on the 150 x 0.9 cm column of Dowex 50-x4 the author estimated 20 kinds of free amino acids and their related compounds isolated from the brain of the hypophysectomized Rattus; and obtained the following results: 1. A marked decrease has been observed in the metabolically active amino acid groups such as aspartic acid, glutamic acid, γ-aminobutyric acid, alanine and serine. 2. Likewise a decrease can clearly be noticed in the content of N-acetylaspartic acid that exists specifically in the brain and in the content of phosphor containing amine, glycerophosphoethanolamine as well as in the glutathione content, the only peptide which has been successfully estimated. 3. In the sutdy of 6 indispensable amino acids such as threonine, isoleucine, leucine, lysine, histidine, and arginine no noteworthy changes can be recognized. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 4-1 1959 脳の遊離アミノ酸について(VIII) イヌ脳各部位の遊離アミノ酸およびその関連物質 1629 1634 EN Nobuhiro Fukai By means of the chromatography on the 150×0.9cm column of Dowex 50-x 4 author estimated various free amino-acids and related compounds isolated from such sites of the brains of dog as the cerebral cortex, white matter, cerebellar hemisphere, caudal nucleus, thalamus, hypothalamus, medulla oblongata, and cerebellar worm; and obtained the following results: 1. It has been found that the content of glutamic acid is low in the white matter, hypothalamus and medulla oblongata, while the aspartic acid content is likewise somewhat low in the white matter but quite high in the medulla oblongata. The content of γ-aminobutyric acid is markedly high in the hypothalamus, followed by that in the cerebellar worm, but in is low in the white matter. 2. The contents of cystathionin and glutathion are markedly high in the thalamus and hypothalamus. 3. The content of N-acetylaspartic acid is high in the cerebral cortex while it is low in the white matter and medulla oblongata. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 102 11-12 1990 N-メチル-D-アスパラギン酸脳室内投与のマウス脳内アミノ酸への影響 1373 1384 EN Yuji Okamura The naturally-occurring dicarboxylic amino acids, L-glutamate (Glu) and L-aspartate, are the principal neurotransmitter candidates for excitatory synaptic transmission in vertebrate central nervous systems. The receptors activated by these amino acids are classified by their most selective and potent agonists, i.e., N-methyl-D-aspartic acid (NMDA), kainic acid, and quisqualic acid. In this study, I examined the effects of NMDA on behavior, electroencephalogram (EEG), and brain amino acids levels after intraventricular injection in mice. When NMDA was intraventricularly injected into mice, running fits were observed 10-30 seconds after injection, followed by a sedative phase and returned to a normal behavior within 15-20 minutes after injection. In the EEG, middle voltage fast waves were observed 10-20 seconds after injection, followed by EEG suppression for a few minutes and the appearance of high voltage slow waves 4-5 minutes after injection. About 20 minutes after the injection the EEG was normal. No spike discharge was observed during this observation. Glu levels increased in the hippocampus during running fits, while GABA levels decreased in the cerebellum and hippocampus before running fits, and increased in the cerebellum 10 minutes after NMDA injection. The taurine level decreased in the striatum before running fits. All amino acids observed recovered to control levels 60 minutes after NMDA injection. These results indicate that the NMDA-induced running fits are not accompanied by spike discharges in the EEG, and are related to Glu and GABA neurons. No potential conflict of interest relevant to this article was reported.

Blackwell Publishing Acta Medica Okayama 1462-5814 8 6 2006 Identification of glycosylation genes and glycosylated amino acids of flagellin in Pseudomonas syringae pv. tabaci 923 938 EN Fumiko Taguchi Kasumi Takeuchi Etsuko Katoh Katsuyoshi Murata Tomoko Suzuki Mizuri Marutani Takayuki Kawasaki Minako Eguchi Shizue Katoh Hanae kaku Chihiro Yasuda Yoshishige Inagaki Kazuhiro Toyoda Tomonori Shiraishi Yuki Ichinose A glycosylation island is a genetic region required for glycosylation. The glycosylation island of flagellin in Pseudomonas syringae pv. tabaci 6605 consists of three orfs: orf1, orf2 and orf3. Orf1 and orf2 encode putative glycosyltransferases, and their deletion mutants, Delta orf1 and Delta orf2, exhibit deficient flagellin glycosylation or produce partially glycosylated flagellin respectively. Digestion of glycosylated flagellin from wild-type bacteria and non-glycosylated flagellin from Delta orf1 mutant using aspartic N-peptidase and subsequent HPLC analysis revealed candidate glycosylated amino acids. By generation of site-directed Ser/Ala-substituted mutants, all glycosylated amino acid residues were identified at positions 143, 164, 176, 183, 193 and 201. Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry (MS) analysis revealed that each glycan was about 540 Da. While all glycosylation-defective mutants retained swimming ability, swarming ability was reduced in the Delta orf1, Delta orf2 and Ser/Ala-substituted mutants. All glycosylation mutants were also found to be impaired in the ability to adhere to a polystyrene surface and in the ability to cause disease in tobacco. Based on the predicted tertiary structure of flagellin, S176 and S183 are expected to be located on most external surface of the flagellum. Thus the effect of Ala-substitution of these serines is stronger than that of other serines. These results suggest that glycosylation of flagellin in P. syringae pv. tabaci 6605 is required for bacterial virulence. It is also possible that glycosylation of flagellin may mask elicitor function of flagellin molecule. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 61 1 2007 Comparison of hepatic enzymes between japanese men with and without metabolic syndrome 31 34 EN Nobuyuki Miyatake Sumiko Matsumoto Hirofumi Makino Takeyuki Numata Short Communication 10.18926/AMO/32912 We compared the levels of hepatic enzymes in 220 Japanese men with metabolic syndrome with those in age and sex-matched subjects without the syndrome. Metabolic syndrome was defi ned by the new criteria published in Japan, and hepatic enzymes, i.e., aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (γGTP), were measured. AST, ALT and γGTP in subjects with metabolic syndrome were signifi cantly higher than those in subjects without the syndrome, and metabolic syndrome was closely associated with hepatic enzymes in this cohort of Japanese men. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 46 2 1992 Mechanisms in the development of limbic status epilepticus and hippocampal neuron loss: an experimental study in a model of status epilepticus induced by kindling-like electrical stimulation of the deep prepyriform cortex in rats. 129 139 EN Koutaro Inoue Kiyoshi Morimoto Keiko Sato Norihito Yamada Saburo Otsuki Article 10.18926/AMO/32652 A new model of status epilepticus (SE), which was induced by intermittent electrical stimulation (20 Hz for 20 sec every min for 180 min) of the deep prepyriform cortex, has been developed in the conscious rat. SE was induced in 9 of 16 rats in the drug-free group. The number of stimulation trains required to induce SE in this status subgroup was 125.6 +/- 12.7 (mean +/- SEM) and the mean duration of self-sustained seizure activity (SSSA) occurring after cessation of the stimulation session was 295.4 +/- 111.4 min. Some animals showed secondary generalized seizures. Significant cell loss was observed in the hippocampal CA3 pyramidal cell layer ipsilateral to the stimulation site and bilateral CA1 areas in the status subgroup compared with the group subjected to sham operation. In addition, there was a significant negative correlation between the duration of SSSA subsequent to the stimulation session and the total number of intact pyramidal neurons observed in the bilateral CA1 and ipsilateral CA3 subfields of the status subgroup. There were significant differences between the status and non-status subgroups with respect to the number of afterdischarges (ADs) and the total AD duration during the stimulation session. Pretreatment with phenobarbital (30 mg/kg) prevented the development of SE and hippocampal cell loss completely. Pretreatment with MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist (0.25 or 1 mg/kg), also prevented hippocampal cell loss, although it did not block SE generation completely, which suggests dissociation of the mechanisms underlying the development of SE and hippocampal damage. These results indicate that prolonged SSSA actually causes hippocampal damage and it is critically dependent upon NMDA receptor participation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 23 6 1969 Experimental isovalthinuria. VII. Experiments with radioactive acetate, valine, and leucine 497 503 EN Yoshio Fjii Article 10.18926/AMO/32528 1. For the settlement of carbon origin of urinary isovalthine, acetic acid-2-C14, valine-U-C14 or leucine-U-C14 was administered to rats together with isovaleric acid as an isovalthinuria inducer, and urinary isovalthine excreted was tested by autoradiography. As the results of which, it was found that these isotopic compounds were not the precursor of urinary isovalthine. Although the isovalthinuria inducing effect of isovaleric acid was fairly diminished by these isotopic compounds, urinary isovalthine was detected by paper electrophoresis. 2. Some metabolic products of these isotopic compounds were also inquired in urine and some tissues. The results were as follows: a) Acetic acid incorporated into urea, aspartate, serine, glutamate, proline, glycine, alanine, ornithine, ethanolamine, r-amino-buthyric acid (brain only), cholesterol and fatty acids. b) Valine incorporated into urinary glutamate and glycine, and tissue cholesterol and fatty acids. Valine was rapidly excreted in urine and found in a very small amount in liver digest. c) Leucine incorporated into urinary aspartate, serine, glutamate and glycine, and tissue cholesterol and fatty acids. 3. Several important problems of isovalthine studies to be elucidated were discussed. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 37 2 1983 Metabolism of 3-mercaptopyruvate in rat tissues. 85 91 EN Shozo Kiguchi Article 10.18926/AMO/32415 Metabolism of 3-mercaptopyruvate was investigated using homogenates of rat heart, liver and kidney. When 3-mercaptopyruvate was incubated with heart homogenate, L-cysteine, L-alanine, S-(2-hydroxy-2-carboxyethylthio)-L-cysteine and 3-mercaptolactate were produced. At the same time, a decrease in the amounts of L-glutamate and L-aspartate was demonstrated. These results indicate that 3-mercaptopyruvate was converted to L-cysteine by cysteine aminotransferase (EC 2.6.1.3), to 3-mercaptolactate by lactate dehydrogenase (EC 1.1.1.27), and to pyruvate by 3-mercaptopyruvate sulfurtransferase (EC 2.8.1.2), and that HCETC and L-alanine were formed from these products. In the presence of liver homogenate, 3-mercaptopyruvate was mainly metabolized by 3-mercaptopyruvate sulfurtransferase; production of L-cysteine was small and HCETC was not formed. The metabolism of 3-mercaptopyruvate in the presence of kidney homogenate was intermediate between heart and liver: a fair amount of L-cysteine was formed, but HCETC was not produced. A peak which corresponds to L-cysteine-glutathione disulfide on the chromatogram of amino acid analysis was present when 3-mercaptopyruvate was incubated with heart or liver homogenate, but not with kidney homogenate. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 63 5 2009 Effect of Brewer's Yeast-Induced Pyrexia on Aminophylline-Elicited Convulsions in Mice 273 280 EN Rika Ochi Katsuya Suemaru Hiromu Kawasaki Hiroaki Araki Original Article 10.18926/AMO/31837 Theophylline-associated convulsions have been observed most frequently in children with fever, but the mechanism is not fully understood. In this study, we investigated the basic mechanism of aminophylline [theophylline-2-ethylenediamine]-induced convulsions and the effects of Brewer's yeast-induced pyrexia in mice. Diazepam (5-10mg/kg, i.p.), a benzodiazepine receptor agonist, significantly prolonged the onset and significantly decreased the incidence of convulsions induced by aminophylline (350mg/kg, i.p.). However, the gamma aminobutyric acid (GABA)A receptor agonist muscimol (1-4mg/kg, i.p.), the GABAB receptor agonist baclofen (2-4mg/kg, i.p.) and the N-methyl-D-aspartic acid receptor antagonist dizocilpine (0.1-0.3mg/kg, i.p.) failed to protect against the convulsions. 20% Brewer's yeast (0.02ml/g, s.c.) increased body temperature by 1.03, and also significantly shortened the onset and significantly increased the incidence of convulsions induced by aminophylline. The anticonvulsant action of diazepam (2.5-10mg/kg, i.p.) on the convulsions induced by aminophylline was reduced by Brewer's yeast-induced pyrexia. The proconvulsant actions of the GABAA receptor antagonists picrotoxin (3-4mg/kg, i.p.) and pentylenetetrazol (40-60mg/kg, i.p.) were enhanced by Brewer's yeast. These results suggest that the anticonvulsant action of diazepam against aminophylline is reduced by Brewer's yeast-induced pyrexia, and that GABAA receptors are involved in the aggravation of the convulsions by Brewer's yeast in mice. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 41 6 1987 Transamination of L-cysteine sulfinate in the growing rat. 279 283 EN Shuichiro Akahori Kohei Ejiri Hirofumi Kanemori Takafumi Kudo Kaoru Sekiba Toshihiko Ubuka Reiko Akagi Article 10.18926/AMO/31737 The enzyme activities involved in the transamination of L-cysteine sulfinate (L-alanine 3-sulfinic acid), L-aspartate and L-cysteine were examined in fetal, neonatal and maternal rat liver and placenta. In fetal and neonatal rat liver, aminotransferase activity was most active with L-cysteine sulfinate as a substrate and was also active with L-aspartate, while activity with L-cysteine was very low. The activity of transamination of L-cysteine sulfinate in rat liver developed in parallel with that of L-aspartate and L-cysteine. The aminotransferase activity markedly increased after the 19th day of gestation, reaching the same value as adult liver on the 3rd day after birth. The ratios of transamination of L-cysteine sulfinate to that of L-aspartate and to that of L-cysteine were constant during development. These observations suggest that L-cysteine sulfinate, L-aspartate and L-cysteine are transaminated by the same enzyme in the rat liver during development. Since placental aminotransferase activity was extremely low compared with that of the liver, it was suggested that the placenta did not play an important role in the transamination of these amino acids during pregnancy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 13 1 1959 Amino acid concentration in different parts of the dog brain 27 30 EN Nikichi Okumura Saburo Otsuki Nobuhiro Fukai Article 10.18926/AMO/31242 The present paper describes each pattern of the free amino acids in different parts of the dog brain determined by ion-exchange chromatography. The parts examined have been the cerebral cortex, cerebral white matter, cerebellar hemisphere, cerebellar vermis, caudate nucleus, thalamus, hypothalamus, and medulla oblongata. Gamma-aminobutyric acid concentration was the highest in the hypothalamus. Glutamic acid showed lower values in the white matter, hypothalamus, and medulla oblongata. Aspartic acid showed lower values in the white matter and caudate nucleus and higher values in the medulla oblongata. Glutathione and cystathionine showed higher values in the thalamus. N-Acetylaspartic acid showed lower values in the white matter and medulla oblongata. Glycine and alanine showed higher values in the medulla oblongata. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 62 1 2008 Critical Differences in Magnitude and Duration of N-methyl-D-aspartate (NMDA) Receptor Activation between Long-term Potentiation (LTP) and Long-term Depression (LTD) Induction 21 28 EN Naoki Taniike Yun-Fei Lu Kazuhito Tomizawa Hideki Matsui Original Article 10.18926/AMO/30989 The induction of both long-term potentiation (LTP) and long-term depression (LTD) in the hippocampal CA1 region is triggered by the activation of N-methyl-D-aspartate (NMDA) receptors and the subsequent postsynaptic intracellular Ca2+ increase. However, how NMDA receptor activation differs between LTP and LTD induction is unclear. In the present study, we examined the eff ects of the magnitude and duration of NMDA receptor activation on the induction of LTP and LTD. Partial blockage of NMDA receptors by a low concentration of aminophosphonovaleric acid (APV)(2 μM) prevented the induction of LTP, but not LTD. In contrast, a high concentration of APV(25 μM) blocked both LTP and LTD. Tetanus stimulation-induced LTP was impaired when hippocampal slices were given the tetanus stimulation for more than 5 min. Under partial blockage of NMDA receptors, the prolonged-tetanus stimulation induced LTD but not LTP. This phenomenon was mimicked by the application of glutamate to the slices. Finally, LTD induced by prolonged activation of NMDA receptors was not aff ected by inhibition of the desensitization of α-amino-3-hydroxy-5 methylisoxazole-4-propionic acid (AMPA) receptors. These results suggest that critical diff erences exist between the induction of LTP and that of LTD in terms of both the magnitude and the duration of NMDA receptor activation. The duration of the increase in intracellular Ca2+ concentration may be critical for determining whether LTP or LTD induction occurs. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 29 4 1975 Studies on the metabolism of beta-hydroxy- aspartic acid 241 247 EN Takuma Ikegami Article 10.18926/AMO/30905 The content of beta-hydroxyaspartic acid was measured in the urine of man and several species of animals. The configuration of urinary beta-hydroxyaspartic acid was deduced to be L-erythro in form by chromatographic comparisons with authentic samples. An increased excretion of urinary beta-hydroxyaspartic acid was observed in cats when serine or thiamine was administered with glycine. Glycine-1-14C administered to rats was incorporated into the urinary beta-hydroxyaspartic acid. The formation of beta-hydroxyaspartic acid in pig-liver homogenate increased in the presence of glutamate and thiamine pyrophosphate. These results were discussed in relation to the author's working hypothesis on the biosynthesis of beta-hydroxyaspartic acid. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 36 3 1982 Purification and characterization of cysteine aminotransferase from rat liver cytosol. 187 197 EN Reiko Akagi Article 10.18926/AMO/30697 Cysteine aminotransferase (L-cysteine: 2-oxoglutarate aminotransferase, EC 2.6.1.3) was purified over 400-fold from the high-speed supernatant fraction of rat liver. The purified enzyme was homogeneous as judged by gel filtration, isoelectric focusing and disc electrophoresis. The molecular weight of the enzyme was about 74,000 by gel filtration and the isoelectric point was 6.2 (4 degrees C). The enzyme catalyzed transamination between L-cysteine and 2-oxoglutarate and the reverse reaction. The optimum pH was 9.7. The Km value for L-cysteine was 22.2 mM, and that for 2-oxoglutaric acid was 0.06 mM. L-Aspartate was a potent inhibitor of the cysteine aminotransferase reaction. The enzyme was very active toward L-alanine 3-sulfinic acid at pH 8.0, and was also very active toward L-aspartic acid (Km = 1.6 mM). Ratios of activities for L-aspartic acid and L-cysteine were essentially constant during the purification of the enzyme. Evidence based on substrate specificity, enzyme inhibition, and physicochemical properties indicates that cytosolic cysteine aminotransferase is identical with cytosolic aspartate aminotransferase (L-aspartate: 2-oxoglutarate aminotransferase, EC 2.6.1.1). No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 49 2 1995 Changes in dopamine D2 and GluR-1 glutamate receptor mRNAs in the rat brain after treatment with phencyclidine. 61 68 EN Hiroaki Tomita Mitsuru Hikiji Yutaka Fujiwara Kazufumi Akiyama Saburo Otsuki Article 10.18926/AMO/30393 In situ hybridization of slide-mounted brain sections from rats subjected to acute and chronic phencyclidine treatment was carried out using synthetic oligonucleotides complementary to dopamine D2-receptor and non-N-methyl-D-aspartate (NMDA) glutamate-receptor-subunit (GluR-1) mRNAs. There was no significant difference in either the D2-receptor or the GluR-1 mRNA levels in any brain region of the acute phencyclidine (10 mg/kg)-treated and control groups. However, chronic administration of phencyclidine (10 mg/kg/day, 14 days) significantly decreased the dopamine D2-receptor mRNA level in the caudate-putamen (by 27%, P < 0.01) and significantly increased the GluR-1 mRNA level in the prefrontal cortex (by 29%, P < 0.001). These results suggest that the chronic pharmaco-behavioral effects of phencyclidine may involve expression of both dopamine- and non-NMDA glutamate-receptor mRNAs. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 49 2 1995 Effect of Picibanil (OK 432) on the Scavenging Effect of Free Radicals Produced during Liver Regeneration in the Rat 75 79 EN Ko Okamoto Keisuke Hamazaki Hiromi Iwagaki Kunzo Orita Akitane Mori Article 10.18926/AMO/30392 We administered a biological response modifier Picibanil (OK-432), attenuated Streptococcus pyogenes, via the dorsal vein of the penis after 70% hepatectomy in rats, and clarified the scavenging effect of Picibanil on free radicals generated in the regenerating liver. A group of 5 rats was intravenously administered with 25 KE/kg of OK-432 after hepatectomy, while the control group was given saline after hepatectomy. Serum levels of aspartate aminotransferase and alanine aminotransferase and the value of thiobarbituric acid-reactive substances in serum and hepatic tissue after hepatectomy were serially measured, and these values were significantly lower in Picibanil treated animals than in control animals. Free radical production in the regenerating liver was also measured by electron spin resonance spectrometry, and OK-432 injection significantly reduced free radical production. These results suggested that OK-432 reduced hepatocellular damage in regenerating liver by inhibiting lipid peroxidation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 38 4 1984 Transaminative metabolism of L-cysteine in guinea pig liver and kidney. 375 380 EN Miyabi Taniguchi Yasuhiro Hosaki Toshihiko Ubuka Article 10.18926/AMO/30307 Transaminative metabolism of L-cysteine was investigated using homogenates of guinea pig liver and kidney. L-Cysteine was transaminated in the presence of 2-oxoglutarate and the homogenate of either liver or kidney. S-(2-Hydroxy-2-carboxyethylthio)cysteine (HCETC) (3-mercaptolactate-cysteine disulfide) was formed by liver homogenate, but the amount was very small. On the other hand, a relatively large amount of HCETC was formed in the presence of kidney homogenate. Transamination between 3-mercaptopyruvate and certain amino acids was catalyzed actively by both liver and kidney homogenates in the presence of L-glutamate. However, more half-cysteine was formed by liver than kidney, and more HCETC was produced by kidney than liver. L-Glutamate was the most potent amino donor, and L-aspartate strongly inhibited the reaction. Results indicate that L-cysteine can be transaminated both in liver and kidney of the guinea pig, and that kidney is more active than liver. 2-Oxoglutarate is the most active 2-oxo acid for cysteine transamination. Oxaloacetate (and aspartate in the reverse reaction) is inhibitory to the reaction. These results are in agreement with the previous conclusion that cysteine aminotransferase is identical with aspartate aminotransferase. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 68 1-4 1956 赤痢菌の代謝に関する研究第2篇細菌代謝に於ける二基質の相互作用 163 172 EN Yoshiyuki Matsuura This study is carried out to determine the mechanism of mutual action between two substrates which act to accelerate bacterial respiration by their mutual action. From the results of some experiments with some strains of B. dysenteriae, such as Sh. dysenteri 3, Sh. flexneri 1. Sh. flexneri 3, two types of mechanism of the action was discovered, they are as follows. (1) In the case of succinate and aspartate, or succinate and glutamate, these combinations of substrates can accelerate the respiration as compared in the case of each substrate alone. The mechanism of this mutual action included aspartate ⇋ glutamate reaction. (2) In the case of couples in which one substrate is glucose, pyruvate, or succinate and another is tartarate, citrate, histidine, tryptophane, tyrosine, or lysine, these couples of substrates can acceletate the respiration too, in spite of the fact that the latter substrates cannot be oxidized when they are added alone to organisms. The mechanism of this mutual action includes the phosphorous metabolism coupling with oxidation, and addition of the substrates such as tartrate, citrate, etc. to glucose, pyruvate, etc. seemed to activate ATP ⇋ ADP reaction. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 5-1 1959 脳の窒素代謝第14篇モノ弗化醋酸ナトリウム投与大黒鼠脳髄アンモニア，グルタミン並びにアミノ酸量 2127 2132 EN Tsuneko Ota Administering the Sodium Monofluoracetate, SMFA, to the rat, the quantitative determination of ammonia and glutamine in the rat brain was made by the Conway's microdiffusion analysis and on the other hand amino acids by the paperchromatography. The results as follow, To wit: 1) In the convulsion stage caused by SMFA administration, ammonia content in its brain was 2.18 mg%, glutamine 63.9 m%, glutamic acid 120.7 mg%, γ-aminobutylic acid 25.2 mg% and aspartic acid 42.8 mg%. 2) About the hourly observation after the SMFA adiministration to the rat. a) Ammonia content in its brain showed gradual increase in 4 hours up to 4 times of control value. b) Glutamic acid content showed always low level in 4 hours but the lowest one in the first one hour. c) Glutamine content also decreased in all 4 hours, remarkably at the first and thlast. d) γ-amino butylic acid content decreased. e) Aspartic acid content increased remarkably in the first 10 minutes, and then decreased. But it showed remarkably increased at the 4th hour again. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 70 12 1958 脳のアミノ窒素第二編死後変化としてのダイコクネズミ脳遊離アミノ酸量の消長 4677 4682 EN Shigeru Yunoue Quantative changes in the contents of amino-nitrogen, ammonia and individual amino acids during the incubation of fresh rat brain tissue were investigated. Suspensions or slices of the fresh brains were incubated at 37℃ , pH 7.4. Amino-nitrogen was estimated by the modified ninhydrin colorimetric method, and ammonia by the Conway's micro-diffusion analysis. Contents of the individual amino acids and the related compounds of the brain suspensions before and after incubation were also determined. Ion exchange chromatography was employed for this purpose. 1) In the suspensions anaerobically incubated, a rapid increase of amino-nitrogen was found; this increase ceased within about one hour after start of the incubation, showing no further increase during the second hour. The liberation of amino-nitrogen was found to be more rapid in the white matter than in the grey matter of the rabbit brain. 2) In the cases of the brain slices, the increase in amino-nitrogen was a little slower and more protracted, being remarkably disturbed by the addition of glucose. The ammonia contents during incubation showed a relatively slow increase without paralleling with the increase of amino-nitrogen. During the period when the tissue samples were prepared at O℃ ., rapid ammonia formation was recognized while amino-nitrogen remained almost constant. 3) Several amino acids such as serine, glycine, alanine. aspartic acid and γ-aminobutylic acid increased after incubation of one hour, glutathione and N-acetylaspartic acid rather decreased. 4) It appears that this remarkable increase in amino-nitrogen observed during a few hours after death might be due to the effect of "neutral proteinase" as reported by Ansell & Richter. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 70 12 1958 脳の窒素代謝第13編 DMAE, LSD, Frenquel投与, 及び.各種薬剤・電撃併用時大黒鼠脳髄アンモニア並びにアミノ酸について 4669 4675 EN Kano Ihara After treating Rattus with various drugs the author measured the amounts of free ammonia and glutamine in the brain of the test animals by Conway's micro-diffusion analysis and the amino acid content by paper chromatography. The results are as follows: 1. In the brain of the Rattus receiving acute administration of DMAE it has been found that the contents of ammonia, glutamic acid, γ-amino butylic acid, and aspartic acid are increased, but the content of glutamine alone is decreased. 2. In the cases receiving acute admins tration of LSD, a slight decrease in ammonia and glutamine has been recognized, but no marked changes in the amounts of glutamic acid and aspartic acid. Only γ-amino butylic acid has been found to have dec reased. 3. In the cases receiving acute administration of Frenquel, ammonia, glutamine, giutamic acid and γ-amino butyli acid are all decreased, whereas only aspartic acid shows no marked changes. 4. In the cases receiving acute administration of Isomytal, the ammonia content in the brain is markedly decreased, but when electric shock is given under this condition, the ammonia content in the brain increases to that above normal. 5. In the cases receiving acute administration of Reserpine, ammonia decseases markedly, but even when electric shock is given under this condition, there is no increase in the amount of ammonia. 6. When electric shock is given to the Rattus whose ammonia content in the brain has previously been increased by administration of Philopon, no further increase in the ammonia content can be elicited. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 70 11 1958 脳の窒素代謝第12編ヒロポン,リタリン,メラトラン投与大黒鼠脳髄のアンモニア並びにアミノ酸について 4219 4224 EN Kano Ihara The author estimated the quantity of ammonia in the brain of the Rattus administered with such drugs as philopon, ritalin or meratran by Conway's diffusion analysis, and also the quantity of amino acids by the paperchromatography. The following are the results: 1. In the case of acute administration of philopon, the amount of ammonia in the Rattus brain increases markedly, while on the contrarily in the case of chronic administration it tends to decrease. Moreover, in the case of chronic administration all amino acids in the brain show a decreasing tendency. 2. In the case of acute administration of ritalin both ammonia and glutamic acid increase in the Rattus brain, whereas in the case of chronic adminstration the brain ammonia rather tends to decrease. 3. In the case of acute adminiattration of meratran, ammonia, glutamic acids, and aspartic acid all increase in the Rattus brain. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 3-2 1959 細菌の五炭糖代謝第1篇発育菌の五炭糖の分解第2篇静止菌の五炭糖の酸化 1335 1358 EN Takashi Akagi Using the growing cells of Sal. typhi Sh. flexneri, Sh. sonnei, E. coli, A. aerogenes, Staph. aureus, Staph. albus and Staph. citreus, all of those were obtained from the departmental stock, the author investigated the effects of ribose, arabinose or xylose on growth as C-source and the decomposition of these pentoses during their growth. Following results were obtained. 1) Any pentoses added on the media containing the minimal essential dose of N-source and vitamins could not support the growth of Sh. sonnei and E. coli. Ribose could be served as C-source for the growth of Sal. typhi, Sh. flexneri, Staph. aureus, and Staph. citreus, while arabinose and xylose could not be so. Any pentose tested served well as C-source on the growth of E. coli when aspartic acid was added at the same time as N-source besides ammonium salt. In the case of A. aerogenes the pentoses showed the same effect even though additional aspartic acid was not present. 2) When peptone was added to media as N-source, any bacteria tested could consume these pentoses in the media. Also it was noticed that Sal. typhi Sh. sonnei, E. coli and A. aerogenes adapted to the pentoses because of their increased consumption of the sugars with the passage of culture generations. However, the adaptation was not found in the case of Staph. aureus, Staph. albus and Staph citreus. Using the resting cells of Sal. typhi, Sh. flexneri, Sh. sonnei, E. coli, A. aerogenes, Staph. aureus, Staph. albus and Staph. citreus, the auther studied oxydation of ribose, arabinose and xylose, and obtained the following results. 1) From the comparative study of pentoses oxidation abilities of the bacteria, grown on nutrient agar media, it was found E. coli and A. aerogenes had relatively great ability to ribose, however, the others showed low abilities to these pentoses. 2) In the case of Staph. aureus, Staph. albus and Staph. citreus, the oxidative abilities to the pentoses greatly depended upon the age of culture, while in the other bacteria, the ability was not so much dependable. 3) Sal. typhi, Sh. flexneri and Sh. sonnei showed slight uptake of oxygen with addition of one of the pentoses, but the uptake of oxygen markedly increased when the pentose was added with glucose at the same time. 4) When culture passed through generations on the media containing any one of the pentoses, any bacteria except Staphylococcus adapted to the corresponding sugar. 5) It seemed that the pentoses were oxidized to pyruvate by any bacteria except Staphylococcns, and pyruvate formed was in turn decomposed thoroughly, but partly it turned to and accumlated as lactate or acetate. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 2-2 1959 脳hexokinaseに関する研究第3編真正癲癇患者大脳皮質のhexokinaseについて 791 798 EN Takahiko Yamada The hexokinase activity in the human cerebral cortex of the epileptics as well as the non-epileptics was measured, and the influences of glutamic acid, glutamine, aspartic acid, asparagine, γ-aminobutyric acid and α-ketoglutaric acid upon the activity were evaluated and compared. The results were as follows. 1) The hexokinase activity in the cerebral cortex of the genuine epileptics is generally decreased, compared with that of the non-epileptics. 2) This decrease in the epiliptics is recovered and increased by asparagine, glutamic acid, γ-aminobutyric acid, aspartic acid and glutamine.　3) α-Ketoglutaric acid markedly inhibits the hexokinase activity even in the epileptics. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 2-2 1959 腦hexokinaseに関する研究第2編潜在性脳局所アナフィラキシー家兎大脳皮質のhexokinaseについて 785 790 EN Takahiko Yamada Latent cerebral local anaphylaxis (LCLA) has been experimentally probed to be an epileptic disposition and a state of arrangement of convulsion by many reports. The author measured the hexokinase activity in the cerebral cortex of rabbits with latent cerebral local anaphylaxis which was experimentally influenced by the use of glutamic acid, glutamine, aspartic acid, asparagine, γ-aminobutyric acid and α-ketoglutaric acid and the following results were obtained. 1) The hexokinase activity in the cerebral cortex of rabbits with LCLA is decreased, compared with that of normal rabbits. 2) Asparagine markedly accelerates the activity, while γ-aminobutyric acid does slightly. 3) Glutamic acid, glutamine or aspartic acid has almost no influence on the activity. 4) α-Ketoglutaric acid shows a marked inhibition to the activity as seen in normal rabbits. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 2-2 1959 腦hexokinaseに関する研究第1編家兎大脳皮質のhexokinaseについて 779 784 EN Takahiko Yamada The hexokinase activity in the cerebral cortex of normal rabbits was measured by Longs method and the influences of fluoride, Ca ion, glutamic acid, glutamine, aspartic acid, asparagine, γ-aminobutyric acid and α-ketoglutaric acid upon the hexokinase activity were also evaluated. The results were as follows: 1) The fluoride shows the maximum inhibition to the hexokinase activity at 0.5M of its concentration, and the inhibition rather decreases at higher concentration. 2) Ca ion shows an increasing inhibition as its concentration increases. 3) When asparagine or glutamic acid is added, the activity is markedly accelerated. 4) γ-Aminobutyric acid accelerates slightly the activity of the cerebral hexokinase and markedly that of the heart muscle hexokinase. 5) α-Ketoglutaric acid markedly inhibits the activity. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 70 7 1958 微生物に対するオーレオマイシンとテラマイシンの作用の比較 2547 2552 EN Yoshiro Yabe Goro Nakayama Sei Hayashi Ryohei Hashimoto Shigetada Ono Both of aureomycin and terramycin belong to the tetracycline, and their action has been considered to be nearly the same. The authors made a comparative study on the action of aureomycin and terramycin and obtained the following results: 1) The respiration of Escherichia coli in the presence of glucose, pyruvate, aspartate and glutamate is markedly inhibited by both of aureomycin and terramycin. The respiration inhibitory action of aureomycin is quantitatively about 3 times higher than that of terramycin. 2) The respiration of Micrococcus pyogenes var. aureus (Terashima) in the presence of glutamate, alanine, pyruvate and lactate is inhibited by both of aureomycin and terramycin. As for the respiration inhibitory action, aureomycin is quantitatively about 3 times stronger than terramycin. 3) The respiration of M. pyogenes var. sureus (Terashima) in the presence of glucose is not inhibited by aureomycin or terramycin, but is rather accelerated by these, particularly by terramycin. 4) As for the growth inhibitory action, aureomycin is somewnat stronger than terramycin. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 2-1 1959 チフス菌の酵素的性状(Ⅰ) 第1編基質無添加に於て振盪した菌体の酵素活性第2編各種基質を加えて振盪した菌の酵素活性 415 432 EN Tetsuya Tagawa Shaking cell suspensions without addition of substrate, O(2)-uptakes were compared in the cases where C source was added as the substrate and in those where amino acids were added as the substrate, after 1, 2.5, 5, and 10 hours respectively; and the following results were obtained: 1. The O(2)-uptake in the case using C source as the substrate is generally diminished in proportion to the length of time the cell suspension was shaken, but the degree of such a diminition varies with substrate. In the case using the C source other than succinate the diminition in O(2)-consumption after the first hour's shaking is marked. In comparing the O(2)-uptake-time curves of shaken cells, on the whole the curve is relatively straight, whereas in the control, cells not shaken, the O(2)-consumption generally decreases by 60 minutes and the curve is a downward curvature. 2. Of amino acids in the case where aspartate or glutamate is used as the substrate, O(2)-uptake rather increases after shaking for 2.5～5 hours. In the case where valine or histidine is used as the substrate, although in the control cells no difference can be seen from endogenous O(2)-utake, shaken cells show differences. 3. The facts mentioned in (1) and (2) seem to indicate that substances existing in cells possiblly playing the role of substrate are consumed by shaking. Shaking after the addition of such a higher C source as glucose and observing cells while a portion of the substrate still remains, the O(2) uptake is greater when the substrate used is such a higher C source or substances closely related to the oxidation pathway. In contrast to this, in the case of cells where the added substance is completely consumed by shaking, the O(2)-uptake is greater when the substances added are such terminal substances of the oxida ion pathway as lactate, pyruvate and acetate. This fact seems to reflect the changes in the arrangement of the enzyme system of cells in the course of oxidation of the subtances added at the time of shaking. In the case of cells shaken after the addition of alanine, aspartate, or glutamate, the O(2)uptake in the cases where substrates are such as aspartate and glutamate besides the substance added at the time of shaking is rather great. This seems to be due to the adaptability of cells to any one of amino acids because of the transamination taking place during the shaking. Moreover, the enzymatic activity of cells is gonerally greater when shaken after the addition of some substances than when shaken without addition of substrate. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 2-1 1959 レプトスピラの代謝に関する研究第2編レプトスピラ・ヘブドマーデイスの呼吸に就いて 405 413 EN Yasuji Izumi In order to investigate the enzyme activity of L. hebdomadis stock-cultured in author's department, the oxidation of some sugars, carbonic acids and amino acids by the resting organism cultured on vovine serum supplemented Korthof's media was studied. And the results were as follows. 1) It was found that L. hebdomadis was capable of aerobic metabolism as like as L. icterohaemorrhagiae. 2) In the light of sugar metabolism, the organism had the higher enzyme activity to hexose oxidation: but it had remarkably low to pentose oxidation. The oxidative activities on carbonic acids and amino acids was lower than that of true bacteria, though the activity on some substrates, i. e. aspartic acid, glutamic acid, pyruvic acid, succinic acid, and lactic acid, was fairly high. 3) The organism showed the transamination reactions between glutamic acid and aspartic acid, and also between glutamic acid and alanine. 4) Although the author caried out the experiment of additional effect of KCN, NaF, monoiodacetic acid, sodium arsenite, Mg(++) and Fe(++) in order to investigate the metabolic pathway of glucose, it could not establish the metabolic pathway so far as the results obtained. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 70 7 1958 Sh.sonnei S型,R型菌の酵素的性状第1編発育菌について 2355 2361 EN Mitsuo Hamano Using S type and R type of Sh. sonnei, those standard strains stocked in our aboratory as test bacteria, the author studied influenes of N and C sources and various vitamins on cell growth and made a comparative study of glucese exidation during the cell growth; and obtained the following results. 1. When glucose is used as C source to which nicotinamide is added and then using aspartate, glutamate, alanine, or glycine separately as N source, it has been found that S type and R type of Sh. sonnei grow well in such media, and aspartate proves to be a specially good N source. 2. When aspartate is used as N source without addition of C source, neither of the two types can grow. However, glucose, gluconate, lactate, pyruvate, or succinate can be used as a suitable C source, but ribose does not serve as C source. 3. Nicotinamide proves to be necessary for promoting the growth of these two types of bacteria, but vitamin B(6) is not necessary. 4. In the still standing culture with fluid medium S type grows better than R type, whereas in the roller tube culture R type grows better than S type. 5. When the accumulated amount of pyruvate, lactate or acetate is compared with the amount of glucose consumed in the still standing culture with fluid medium using pepton as the N source and glucose as the C source, it has been found that the accumulation of these substances in the case of S type is greater than in the case of R type, indicating that the complete oxidaton of pyruvate is not carried out smoothly. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 1 1959 脳のglucose代謝におよぼすamino酸の影響に関する研究第2編癲癇患者大脳皮質のglucose代謝およびそれにおよぼす種々のamino酸の影響について 313 318 EN Yasuhisa Yamamoto The influences of the free amino-acids upon the glucose metabolism were investigated in the cerebral cortex removed from the epileptogenics and non-epileptogenics. Glucose metabolism decreased in the epileptogenic cerebral cortex, compared with the nonepileptogenic one. In the non-epileptogenic cerebral cortex, these free aminoacids accelerate the utilization of glucose, in the following order of γ-aminobutyric acid, aspartic acid, asparagine, glutamine, glutamic acid from the most to the least, while in the epileptogenic one in the order of aspartic acid, glutamic acid, asparagine, γ-aminobutyric acid and glutamine. These amino-acids have more pronounced function to accelerate the glucose metabolism in the epileptogenic brain than the nonepileptogenic. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 1 1959 脳のglucose代謝におよぼすamino酸の影響に関する研究第1編潜在性脳局所anaphylaxis家兎大脳皮質のglucose代謝およびそれにおよぼす種々のamino酸の影響について 305 311 EN Yasuhisa Yamamoto There are many kinds of free amino-acids in the brain, most of which are glutamic acid, glutamine, asparatic acid. asparagine, γ-aminobutyric acid etc. The author has investigated the influences of these amino-acids upon the glucose metabolism in the brain of the normal and the cerebral local anaphylactic (C. L. A.) rabbits. Glutamic acid, glutamine and γ-aminobutyric acid accelerate the utilization of glucose in the brain of the normal as well as the C. L. A. rabbits, aspartic acid and asparagine accelerate that of glucose in the C. L. A. rabbits, while they have no influence on that in the normal. It is clarified that all of these amino-acids have the function to restore the decreased utilization of glucose in the C. L. A. rabbits to more than the normal level. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 70 6 1958 脳の窒素代謝第11編塩化アンモン投与大黒鼠脳髄アンモニア並びにアミノ酸量 2285 2289 EN Saburo Kawata In case of the intraperitoneal application of ammonium chloride, ammonia of the rat brain was measured by Conway's microdiffusion method, and amino acid by paperchromatography; the following results were obtained. 1) During the ammonium chloride convulsions (induced by injection of 1ml. of 10% NH(4)Cl), the ammonia and aspartic acid contents of the rat brain increased remarkably, while glutamic acid, glutamine and γ-amino butylic acid contents decreased. 2) Ammonia and amino acids were estimated in 3 hours after NH(4)Cl injeetion (1ml. of 5% NH(4)Cl), and the following data were obtained. a. Ammonia level remarkably rose five minutes after injection, and gradually returned to normal level 3 hours after. b. Glutamic acid decreased. c. The rise of glutamine level found 10 minutes to 1 hour after the application. d. γ-amino butylic acid decreased. e. Aspartic acid level rose on early period. The Conclusion is as follows: 1) In the rat brain, the free ammonia increased after NH(4)Cl injection. 2) Ammonia increased after NH(4)Cl injection was probably reduced, initially by aspartie acid synthetase system and thereafter by glutamine synthetase syestm. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 70 6 1958 脳の遊離アミノ酸について (Ⅴ) 冬眠状態におけるクサガメ脳の遊離アミノ酸およびその関連物質 2135 2138 EN Tatsuya Aoyama From the comparative biochemical standpoint free amino acids and related substances have been isolated and quantatively analyzed from the brain of the common turtle (Geoclemys reevesii) in hibernation, the animal belonging to the reptile family, and the following are the results. 1. In comparison with those in the brain of mammals, aspartic acid, glutamic acid, alanine, serine, and glycine have been found only in extremely small quantities. 2. The quantity of both taurine and threonine has been less than either of them found in the brain of a catfish or a rat. 3. No isoleucine, leucine, lysine, nor histidine can be detected, and unidentified ninhydrin positive substances such as X(4), X(5), and X(6) have been recognized. 4. Despite the small quantity of glutamic acid, the amount of γ-aminobutyric acid has been about the same as found in the brains of mammals. 5. The total quantity of amino-N is less than that in the brain of catfish, frog, or rat. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 70 6 1958 脳の遊離アミノ酸について(Ⅳ)冬眠状態のカエル脳遊離アミノ酸およびその関連物質 2131 2134 EN Tatsuya Aoyama Attempts have been made from comparative biochemical standpoint to isolate and determine free amino acids in the brain of the frog (Rana nigromaculata) in hibernation, the animal belonging to the amphybian family by the ion exchange cbromatography, and the following are the results: 1. Aspartic acid, glutamic acid, alanine, and serine have been found markedly decreased as in the case of the catfish brain as compared with those in the mammalian brains. 2. Taurine has been found more markedly decreased than either in the ease of the catfish brain or of the rat brain. 3. The amounts of unidentified substances X(1), X(2) and acidic amino-group show the values intermediate between those in the catfish brain and those in the rat brain. 4. The amount of γ-aminobutyric acid does not show any marked difference in the brains of all the animals tested. 5. Glycine, isoleucine, leucine, threonine, and lysine yield the values closer to those found in the mammalian brains than those in the catfish brain. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 1 1959 細菌の合成培地に関する研究第二編葡萄球菌.サルモネラ菌属及び赤痢菌属の液体合成培地に於ける発育に就いて 81 88 EN Hirotaka Nakanishi Using the fluid media containing any one member out of eleven amino acids and nicotic acid or certain combination of them, the author studied the effect of these nitrogen sources on the growth of some species of Staphylococcus, Salmonella and Shigella, that were the departmental stock of author's laboratory. And the following results were obtained. 1) It was found that Staph. aureus and Staph. albus required many species of amino nitrogen and growth factors. The author failed to culture them in the media described above, for the lack of some required components for their growth. 2) Sal. enteritidis and Sal. typhi murium could grow sufficiently in the media containing merely ammonium nitrogen, but the extra addition of cystine to the media showed the marked increase of growth. 3) The growth of Sal. typhi 57 S and R were accelerated by the addition of sulfur containing amino acids, cystine and methionine, And also glutamic acid and aspartic acid could serve to these micro-organisms as nitrogen source. Sal. paratyphi A reqired cystine as the essential amino acid, but in the case of Sal. paratyphi B and C it was effective to add glutamic acid and phenylalanine to the basal media. 4) Nicotinic acid seved as the essential factor to the Shigella species, Shigella sonnei and Shgella flexneri 2a; in addition, aspartic acid showed the stimulation for growth. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 73 10-12 1961 γ-アミノ酪酸の代謝に関する研究第2編てんかん脳切片による(14)C-γ-Aminobutyric aicdの代謝について 777 784 EN Kazuaki Uno Studies were carried out to clearfy GABA metabolism in the brains of an epileptic, the latent cerebral local anaphylactic (L. C. L. A.) rabbit and ep-mouse administered with (14)C-GABA. 1) Incubated with a brain slice, radioactivity of (14)C-GABA was slightly detected in glutamic acid, aspartic acid and glutamine in the incubation medium. 2) In this case, most of the radioactive carbon of GABA was converted into (14)CO(2). 3) The epileptic brain appeared to decreased in the (14)CO(2)-activity, compared with the non-epileptic. In case of the epileptic brain, the activity in the focus was lower than the one in the non-focus. 4) The study with L. C. L. A. rabbit and ep-mouse could not manifest any difference in GAGA metabolism in contrast to the normal control groups. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 70 4 1958 脳の窒素代謝第10編トランキライザーの大黒鼠脳髄アンモニア並びにアミノ酸に及ぼす影響について 1341 1345 EN Shoji Fujita In the case of meprobamate application and reserpine injection as tranquilizing treatment, the content of ammonia in the brain was determined by Conwy's micro-diffusion method while that of amino acid by paper chromatography; and the following results were obtained: 1) After meprobamate application per os (1g. per dose), the contents of ammonia. glutamic acid and γ-amino-butylic acid decreased, while those of glutamine and aspartic acid increased. 2) In the group given meprobamate for successive days (350 mg-400 mg/kg), the content of ammonia increased, whereas those of glutamic acid, glutamine, γ-amino-butylic acid and aspartic acid less markedly. 3) In the case of reserpine injection (0.4 mg./kg), ammonia decreased markedly and glutamic acid and γ-amino-butylic acid less markedly. 4) In the group receiving reserpine injections for successive days (0.025 mg/kg/day), the content of ammonia showed a decrease, while that of aspartic acid an increase. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 70 4 1958 脳の窒素代謝第9編興奮剤及び鎮静剤の大黒鼠脳髄アンモニア並びにアミノ酸に及ぼす影響について 1337 1340 EN Shoji Fujita In the determinations of the content of free ammonia in the rat brain by Conway's micro-diffusion method, and that of free amino acid by paper chromatography, the author obtained the following results. 1) During the marked excitement caused by 20% caffeina et sodii benzoas injections (0.5cc per dose), the content of ammonia increased while those of glutamic acid and glutamine decreased. 2) During the deep sleep caused by amobarbital injections (50mg/kg), the content of ammonia decreased, whereas those of glutamine and aspartic acid increased. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 70 4 1958 脳の窒素代謝第8編実験的衝撃の大黒鼠脳髄アミノ酸に及ぼす影響について 1331 1336 EN Shoji Fujita In the determinations of glutamic acid, glutamine, γ-aminobutylic acid, and aspartic acid in the rat brain by paper chromatography, the author obtained the following results: 1) In the normal rat brain, the value determined for glutamic acid was 158.4 mg.%: for glutamine 95.5 mg.%; for γ-aminobutylic acid 35.2 mg.% ; and for aspartic acid 30.8 mg.%, respectively. 2) After the convulsion caused by electro-shock, the contents of glutamic acid and γ-amino-butylic acid in the brain showed a decrease. 3) In the animals treated with electro-shocks for 13 to 18 days (2 times/day), the content of γ-amino-butylic acid in the brain decreased, while that of glutamine an increase, and aspartic acid increased markedly. 4) During the coma caused by insulin shocks, the content of glutamic acid showed a decrease, while that of glutamine an increase, and aspartic acid increased markedly. 5) In the group given repeated insulin shocks, glutamic acid drecreased while glutamine increased; and aspartic acid increased markedly. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 70 3 1958 無カタラーゼ血液症患者血液に対する2, 3細菌の作用について第2編菌の呼吸に対する赤血球の影響 913 921 EN Mikitaro Kawata As previously reported in Part Ⅰ the author found that hemoglobin had tendency to show the production of MetHb and the decolorization remarkably when Streptococcus hemolyticus, Streptococcus viridans, and Diprococcus pneumoniae Ⅰ, Ⅱ and Ⅲ were cultured in the medium using the blood of acatalasemic patients. These changes clearly have indicated that the blood of these patients lacking in the catalase is unable to dispose of hydrogen peroxide (H(2)O(2)) produced by bacteria and subsequently Hb is oxidized to form MetHb and with progress of oxidation the constituents of the blood seem to turn to decolorization substances such as propentodyopent. This time with a view to clarify this point still further, the author studied action of still bacteria en erythrocytes of the normal and the patients, and from the results of this study arrived at the following conclusion. 1) Diprococcus pneumoniae Ⅱ, Ⅲ and Streptococcus viridans markedly accumulate H(2)O(2) during oxidation process of glucose. 2) When glucose is used as substrate loaded with acatalasemic erythrocytes and shaken, in the case of Diprococcus pnemoniae Ⅰ, Ⅱ, or Streptococcus viridans, a marked production of MetHb has bean observed, when normal erythrocytes are loaded, the production of MetHb has been extremely small as compared with each of these bacteria in the case of the acatalasemic erythrocytes. When pyruvate, succinate, or aspartate is used as substrate, the influences of each of these bacteria on erythrocytes are on the whole quite small. 3) Productivity of MetHb and decolorization by bacteria have a parallel relationship with the accumulation of H(2)O(2). 4) Using glucose as substrate, influences of Diprococcus pneumoniae Ⅱ on the respiration of erythrocytes are as follows. a. In the case where erythrocytes are not loaded (the control) O(2)-consumption decreases by 60-90 minutes. b. In the case where acatalasemic erythrocytes are loaded, so long as Hb exists, O(2)-consumption continues to rise. c. In the case where normal erythrocytes are loaded, up to 60 minutes O(2)-consumption is comparatively lower than that of the control but it does not fall even 120 minutes later. d. On examining H(2)O(2) in solution after these reactions, an extremely minutes quantity of it has been traced in the case of loading acatalasemic erythrocytes, while none can be traced in the case of loading normal erythrocytes. e. Thiourea and cysteine have been found to completely recompensate whatever influences exerted upon O(2)-comsumption of bacteria by acatalasemic blood. 5) After studying color changes of the erythrocytes to which H(2)O(2) of various concentrations had been adden, the results thus obtained were quite identical with those which erythrocytes had been influenced by respiring bacteria. 6) From these facts as far mentioned it may be assumed that the influences of respiring bacteria upon the acatalasemic erythrocytes are due to the action of H(2)O(2) produced by bacteria. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 70 3 1958 Micrococcus pyogenes var. aureus （寺島）の終末代謝系の一生理面 691 695 EN Yoshiro Yabe Goro Nakayama Hiroyuki Ohnishi Sei Hayashi In 1957, Yabe reported that the combined administration of glutamate and glucose markedly accelerated the respiration of Micrococcus pyogenes var. aureus (Terashima) over the sum of those in each of the two substrates, and that this phenomenon was due to the important role of glutamate as a sole sparker or entering site of the citric acid cycle of M. pyogenes var. aureus (Terashima). In the present experiments, the authors investigated this phenomenon in regard to pH. In the presence of glutamate and glucose, oxygen consumption or carbon dioxide evolution was nearly the same at all pHs tested, whereas ammonia formation was the best at pH 6.2, which was the optimum for glutamate oxidation by M. pyogenes var. aureus (Terashima); this result seems to sustain the conclusion given by Yabe. For all of glutamate, aspartate and alanine, the oxidation optimum pHs were lower in M. pyogenes var. aureus (Terashima) than in pyogenes var. albus and citreus. From thsee results, it is easily inferred that the cytoplasmic membrane of M. pyogenes var. aureus (Terashima) is a pretty peculiar one compared with those of the other two micrococci, and that these peculiar physiological properties of the cytoplasmic membrane have something to do with the previously reported peculiar aspect of the citric acid cycle of M. pyogenes var. aureus (Terashima). No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 73 4-6 1961 痙攣によるAldolase及びTransaminaseの変動に関する実験的研究第1編正常家兎および脳局所アナフイラキシー家兎大脳皮質のAldolase活性について 219 224 EN Koji Oda The aldolase activities in the cerebral cortex of normal rabbits and rabbits with latent cerebral local anaphylaxis (LC LA) were measured by using Bruns' method, and influences of glutamic acid, glutamine, aspartic acid, asparagine, and γ-aminobutyric acid on the aldolase activities were evaluated. It has been experimentally probed that LCLA is an epileptic disposition and a state of arrangement of convulsion. The results were as follws. 1) The aldolase activity in the cerebral cortex of rabbits with LCLA is decreased, compared with that of normal rabbits. 2) Glutamic acid accelerates the activity of the cerebral aldolase of normal rabbits. 3) Asparagine accelerates the activity of the cerebral aldolase of LCLA rabbits. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 72 5-7 1960 電気刺戟（in vitro）の脳物質代謝におよぼす影響第3編電気刺戟（in vitro）の大脳トランスアミネーションにおよぼす影響 1463 1469 EN Hisashi Kumashiro 1) ダイコクネズミ,タイワンザル,ヒト脳の大脳ホモジネートおよび大脳皮質切片を用いて電気刺戟(in vitro)のトランスアミネーションにおよぼす影響をみた. 2) ダイコクネズミ大脳においてはAsGT活性は電気刺戟によつてホモジネートでは14.6%切片では9.6%阻害された.すなわちホモジネートの方が切片より阻害率は著明なようであつた.またAIGT活性は電気刺戟によつてホモジネート,切片とも著変なく,γAGT活性は電気刺戟によつてホモジネート,切片とも阻害傾向を示した.そこでAIGTは酵素系が異なるためではないかと推論した.また反応率はいづれの場合も切片の方がホモジネートより減少していた. 3) タイワンザル大脳皮質ホモジネートにおいてはAsGT活性は電気刺戟によつて平均約11%阻害された.またヒト健常大脳皮質切片においてはAsGT活性は電気刺戟によつて平均約11.3%の促進をみ,ヒト萎縮大脳皮質ホモジネートにおいては殆ど変化をみなかつた.また反応率を比較するとヒト健常大脳皮質切片ではダイコクネズミの切片の場合に比し対照時,刺戟時ともに約20%高く,ヒト萎縮大脳皮質ホモジネートではダイコクネズミのそれに比しやや低い値を示した.すなわち萎縮脳のAsGT活性の低下が考えられる. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 75 10 1963 ep系マウスの脳代謝におよぼすparabiosisの影響に関する実験的研究第3編 ep系マウス大脳のglutamic acid,γ-aminobutyric acidおよびaspartic acid含有量におよぼすparabiosisの影響について 827 833 EN Sadahiko Masukawa Biochemical changes as to amino acid metabolism were investigated in the brain of an ep-mouse, having had convulsive seizures, after parabiosis formation with a CF(1)-mouse, one of the normal other species, and the results of this experimeot were as follows: 1. Glutamic acid content was small in the brain of the ep-mouse compared with the CF(1)-mouse. They were approaching between the two levels 6 days after the procedure. Then, they were decreased below the preparabiosis level, showing insignificant defference between the both contents at the 12 th postparabiosis day. 2. GABA content was large in the brain of the ep-mouse compared with the CF(1)-mouse, but both contents were averaged between the levels 6 days after the procedure. They were recovered to the preparabiosis level of the CF(1)-mouse at the 12 th postparabiosis day. 3. Aspartic acid content was slightly large in the brain of the ep-mouse compared with the CF(1)-mouse. The difference was minimized after the procedure, and recovered to the preparabiosis level of the CF(1)-mouse at the 12 th postparabiosis day as in the case of GABA content. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 72 5-7 1960 脳の遊離アミノ酸について(XIII) ヒト脳各部位の遊離アミノ酸およびその関連物質 1299 1306 EN Hirosuke Nishioka By means of ion exchange column chromatography the author carried out quantitative analyses of 14 kinds of free amino acids including the related compounds using the brain of the person who died of acute loss of blood. The parts of the brain used for the analysis were frontal cortex, corpus callosum, caudate nucleus, globus pallidus, thalamus, hypothalamus and medulla oblongata. The results are as follows. 1. In corpus callosum which contains little cellular components extremely minute quantities of phosphoethanolamine, aspartic acid, glutamic acid and γ-aminobutyric acid could be detected. 2. In globus pallidus a surprisingly large quantity of γ-aminobutyric acid could be found and it was far greater than that contained in hypothalamus. 3. In medulla oblongata only small quantities of phosphoethanolamine, aspartic acid, and glutamic acid could be detected. Likewise γ-aminobutyric acid was found not so abundant. This seems to be due to the fact that the present experiment was conducted with medulla oblongata including white matter. 4. Although only in a small quantity, cystathionine could be assayed in all these parts except globus pallidus and thalamus. 5. Even from the comparative biochemistry the present quantitative analyses gave an interesting contrast to the values obtainable in the brains of lower animals. 6. Although it was difficult to recognize any distinct difference in the pattern of amino acids between the adult brain and the infant brain, there was a clear-cut difference in the amino acid pattern of the adult brain and that of the fetal brain. Namely, in the adult human brain there exist far greater quantities of aspartic acid, glutamic acid, γ-aminobutyrie acid, and N-acetylaspartic acid than those in the fetal brain and conversely far less quantities of phosphoethanolamine and taurine than in the latter. Likewise tyrosine detected in the fetal brain could not be recognized in the adult human brain. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 72 5-7 1960 脳の遊離アミノ酸について(Ⅻ)甲状腺剔除の脳遊離アミノ酸およびその関連物質におよぼす影響 1293 1298 EN Hirosuke Nishioka With the purpose to study the influence of thyroidectomy on the free amino acids and the related compounds the author performed the assay of 11 of these substances by ion exchange column chromatography, using the rat brains as the material. As the result it has been found that aspartic acid, glutamic acid, alanine, serine, N-acetylasparticacid, and glycerophosphoethanolamine, the substances that were decreased in the brains of hypophysectomized animals, have been maintained at the normal level on thyroidectomy. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 72 3 1960 微生物の呼吸に対するオーレオマイシン，クロロマイセチン及びストレプトマイシンの作用 927 931 EN Kiyoshi Kawai Toyozi Matsumoto Kakushi Honmatsu Kengi Akiyama This experiment was performed to investigate the effect of aureomycin, chloromycetin, and streptomycin upon the oxidation of several substrates by Sh. flexneri 2a and E. coli communis. The results are as follows: 1) A level of 200γ/ml aureomycin markedly inhibits the oxygen uptake with substrates such as glucose, pyruvate, glutamate, and aspartate. The inhibitory rate has no relation to the preincubation time of a mixture of aureomycin and a cell suspension. 2) A high concentration (200γ/ml) of chloromycetin slightly inhibits the oxidation of amino acids such as glutamate and aspartate. The inhibitory rate has a relation to the preincubation time of a mixture of chloromycetin and whole cell suspensions. 3) A level of 200γ/ml streptomycin slightly inhibits the oxidation of glutamate and aspartate by E. coli, but it does not affect the oxidation of glucose and pyruvate by this organism. The oxidation of proposed substrates by Sh. flexneri 2a is not also prevented by streptomycin. Even though streptomycin is added to the original cell suspension before the substrates and preincubated for an hour, the results are the same. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 72 3 1960 微生物の代謝に対するストレプトマイシンの作用 921 926 EN Kiyoshi Kawai Toyozi Matsumoto Kakushi Honmatsu This experiment was attempted to investigate the inhibitory action of streptomycin. The organism used is Shigella flexneri 2a. The results are as follows: 1) Even under a level of 200γ/ml streptomycin, it cannot inhibit the oxidation of pyruvate, succinate, fumarate, malate, glutamate, and aspartate by whole cell suspensions. 2) When glutamate is added to a cell suspension that has previously been permitted to oxidize fumarate, an immediate increase in oxygen consumption is observed. This increase is scarcely prevented by streptomycin. 3) The oxidatin of a mixture of glucose, glutamate, and 10(-3)M Mg(++) by a cell suspension is prevented by streptomycin level of 200γ/ml. 4) Streoptomycin prevents especially aerobic growth of this organism in the synthetic medium and results in an increased accumulation of pyruvate as a metabolic product. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 72 3 1960 ストレプトマイシン耐性赤痢菌の生理学的研究第2編ストレプトマイシン耐性赤痢菌駒込ＢⅢのピルビン酸代謝と終末呼吸系 901 913 EN Kiyoshi Kawai Following the previous reports, the author carried out the experiment to elucidate the difference in the pyruvate oxidation and its terminal respiration system between resistant and susceptible Sh. flexneri 2a. 1) The oxidation rate of pyruvate by resistant strain is considerably less at every pH than by susceptible strain. The pH optimum for oxidation of pyruvate of resistant strain is pH 5.6-6.0, whereas that of susceptible strain is pH 7.0-7.5. 2) The consumption rate on pyruvic acid substrate by resistant strain is significantly less than by susceptible strain. 3) Both resistant and susceptible strains oxidizes pyruvic acid via succinate. Pyruvate accumulates during the oxidation of the tricarboxylic acid cycle intermediates such as succinate, malate, fumarate, α-ketoglutarate by resistant and susceptible strains. 4) Aspartic-glutamic transamination has been demonstrated in susceptible strain under aerobic condition with both aspartic acid and glucose added. 5) The oxidation of pyruvate of susceptible strain can be accerelated more rapidly by divalent metal ions such as Mg⁺⁺, Fe⁺⁺, Mn⁺⁺ than that of resistant strain. 6) Panthotenate accerelates more reasonably the respiration of pyruvie acid by susceptible strain than by resistant strain. 7) The significance of these results in relation to the presence of the citric acid cycle in the organism is discussed, and it is considered possible that an significant difference in metabolic activities between resistant and susceptible strains exists in the metabolic pathway from pyruvate to succinate in the citric acid cycle. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 72 2 1960 脳のトランスアミナーゼ第2編各種向精神・神経薬のダイコクネズミ脳組織トランスアミナーゼ活性に及ぼす影響 515 520 EN Masaya Ono ダイコクネズミ脳homogenateを用い，グルタミン酸-アスパラギン酸トランスアミナーゼ（GAT）活性に及ぼす18種の向精神薬，および3種の向神経薬の影響を測定した. 1. フエノチアジン系向精神薬は， Prochlorperazineを除く他の6種はいずれもGAT阻害を示し，阻害作用はChlorpromazineに最も強かつた. Chlorpromazine S-oxideはChlorpromazineに比してGAT阻害作用は著しく弱い. 2種のフエノチアジン系向神経薬はGAT活性に影響をみなかつた. 2. AzacyclonolはGAT阻害を示し， LSD-25は高濃度で阻害を示したが低濃度では影響を与えなかつた. 3. 中枢刺戟剤4種のうち， PipradrolとDMAEは促進， Methylphenidateは影響なく， Tofranilは阻害を示した. 4. バルビツール酸系睡眠剤AmobarbitalとPhenobarbital，非バルビツール酸系睡眠剤MethyprylonとGlutethimideは，すべて阻害を示した.しかるにバルビツール酸拮抗剤BemegrideはGATに無影響であつた.抗てんかん剤Primidoneは阻害を示した. 5. 実験に用いた中枢抑制剤13種のうち12種が阻害を示した. 6. GATに及ぼす作用において， ImipramineとChlorpromazineの類似， DiethazineやPromethazineとChlorpromazineとの差異を，化学構造における2個のN原子間の距離の一致と相異に対応すると考えた. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 72 1 1959 コレラ菌の酵素活性に対する免疫血清の影響第1編 O2消費に対する免疫血清及び補体の影響第2編溶菌にともなう酵素活性の変化 95 108 EN Toyozi Okada Part I Effect of Immune Serum and Complement on O(2) Uptake Using the 3 strains of Vibrio cholera, original strain (INABA's strain), intermediate variant strain (HIKOZIMA's strain) and variant strain (OGAWA's strain), the author studied the effect of immune serum and complement on O(2)uptake of the resting cells of these microorganism. Immune serum was added into the resting cell suspension, in which complement was added in an experiment and was not in another experiment, in a various concentration with substrate. And obtained the following results 1) With absence of complement O(2) uptake was inhibited to a slight degree by the addition of immune serum. The inhibition was increased. carrespondingly with the concentration of the serum This findings was supposedly due to the agglutination of bacteria by the action of the immune serum. 2) In the presence of complement, O(2) uptake was also inhibited by the addition of immune serum; especially, strongly inhibited at a low concentration of that, i.e. in dilutions of 1:300-1:400. The inhibition was supposed to be arisen from the lesion on the cells being to be bacteriolysis shertly after that. Part Ⅱ Enzyme Activities Affectad by Bacteriolysis Using the 3 strains of Vibrio cholera as in the part I, the author observed the changes on the enzyme activities of the bacterial cells by affecting the cells by means of suspension into various media or immune reaction. The following results were obtained. 1) The enzyme activities were not so decreased by the washing of the cells with saline added phosphate buffer. But the activities and the numbers of surviving cells were markedly decreased in the case of the washing with saline unadded phosphate buffer, saline solution or distilled water. 2) The enzyme activities were decrealed proportionally to the affection time of immune serum and complement, and eventually qacteriolysis occured. This finding was most distinctive in dilutions of 1:100-1:300 of serum. 3) The decrease of oxidation capacity by bacteriolysis was differ in the substrate oxydized. That was very prominient in the case of glucose, pyruvate and aspartate, while that was rather slight at the oxidation of lactate, succinate and cysteine, and the presence of the oxidation capacities was also found in the centrifuged supernatant of bacteriolysed cells. 4) The deaminative and the desulfhydrative abilities for cysteine were retained after the lysis of bacteria, but these for formation of indol were not found at that state. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 77 7 1965 緑膿菌産生色素 "Pyocianine" に関する研究―特にPyocianine生合成に影響する因子について― 1017 1023 EN Saizo Sakano Pseudomonas aeruginosa produces the two pigments, namely Pyocianine and Fluorescin. The Pyocianine is bluish green pigment and is derivative of phenazine pigment. In this paper, the physiological factors that give influences on the biosynthesis of Pyocianine by Pseudomouas aeruginosa in culture will be presented. 1. Pseudomonas aeruginosa required glycerine as a nitrogene source for the biosynthesis of Pyocianine. In a case that glucose was used as carbon source, the addition of magnesium ion was essential. 2. Within alanine, glutamate and aspartate on which the author examined, only alanine was of effective as nitrogen source for the Pyocianine synthesis. 3. The following results have been investigated by the studies on the atmospheric condition. Pseudomonas aeruginosa produced the pigment at a aerobic condition in the chemically satisfactory culture media, but could not produce at anaerobic condition in any culture media. 4. In the acidic media below pH 6.0, the growing of bacteria was very slight and the Pyocianine could not be produced. Moreover, the pigment did not be synthesized when the pH was descended rapidly, even if the startiag pH of the medium was neutral or slight basic. 5. The growing of the bacteria is indispensable for the synthesis of Pyocianine, then the resting cells could not synthesize the pigment. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 80 3-4 1968 脳灌流法による脳血流障害の研究第2編〔U-(14)C〕グルコースを用いた血流障害時の脳代謝 435 444 EN Katsusuke Mitsunobu The brain was perfused with artificial blood containing [U-(14)C] glucose, and then induced the disturbances of cerebral blood flow as in the previous report. The changes in the glucose metabolism of the brain were studied by measuring oxigen consumption, carbon dioxide formation, glucose uptake and lactic acid output as well as the contents of glucose metabolites and their radioactivities. The results are presented as follows. 1. In the case where the cerebral blood flow is decreased 20% or less, the cerebral oxygen consumption maintains approximately a constant level; where the decrease is over 40% it decreases; and in the decrease of 20-30% both of the above phenomena can be observed. 2. As for carbon dioxide formation, likewise when the decrease is over 40%, the amount of carbon dioxide formed is decreased. 3. The glucose uptake is 0.44μmole in average before the cerebral blood flow is decreased, it is 0.12μmole 32-39 minutes after the cerebral blood flow is decreased, showing the decrease in proportion to the lapse of time. In addition, when the decrease of cerebral blood flow is over 40%, there is observed a decrease in the glucose uptake. With the lactic acid output there is observed no fixed tendency. 4. In the brain with blood flow disturbances the glycogen content is decreased to 1.65μmole. 5. The lactic acid content of the brain shows a tendency to increase when the cerebral blood flow is low. 6. The relative specific activity of metabolites in the brain under the diminished blocd flow, is found to be glucose 100%; lactic acid 45%; and in comparison to 63-75% of lactic acid in standard brain perfusion, the decrease in the radioactivity of lactic acid is marked in the brain with blood flow disturbances. This means that the contribution of non radioactive endogenous substances to the glycolytic process has been potentiated as compared with that in normal state. 7. The relative specific activity of glutamic acid, aspartic acid, glutamine and respiratory carbon dioxide are 30%, 32%, 17% and 20% respectively. In the standard perfusion these values are high in the high level of EEG, respective values being 80%, 75%, 61% and 55%, and it is known that the lower the EEG level, the lower is such ratios. However, these values in the brain with blood flow disturbances, agree approximately with those values in the brain with low function. 8. The relative specific actiyity of γ-amino butyric acid is 14% , being lower than that in the standard brain perfusion where the brain function is low. 9. The relative specific activity of glycogen, while it shows a big standard deviation, is about 22%, giving a considerably higher value than what has been expected. Even from the decrease of the glycogen content in the brain, it can be surmised that the involvement of glycogen in the energy metabolism in the brain under the blood flow disturbance is hightened. 10. These results seem to indicate that in the glucose metabolism of the brain with blood flow disturbances, there occur general disturbances of glucose uptake, glycolytic pathway and the citric acid cycle. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 79 9-10 1967 U-(14)C-グルコースを用いた脳のアミノ酸タンパク代謝の研究第2編Infusion法及び脳灌流法による正常ネコ脳と亜急性圧迫ネコ脳のネンブタール麻酔下におけるアミノ酸代謝について 763 770 EN Buntaro Omori In the previous paper dealing with the protein metabolism as well as the structural chemical aspects of the brain proteins in normal cat brain and the brain under chronic compression by means of infusion method, it was reported that organic changes of the brain affect the protein metabolism. This communication briefly describes the results of the experiment conducted by the infusion method on the amino acid metabolism studied with the use of [U-(14)C]-glucose while comparing with the same metabolism in normal cat brain. Further the effect of the functional changes mainly induced by Nembutal on the glucose metabolism in the brain was studied by means of brain perfusion. and this effect was compared with the effect of Nembutal anesthesia as studied by infusion method. The study was also focused on the metabolism of glutamic acid and aspartic acid which are the protein components of crude mitochondrial fractions in the brains of those placed under subacute compression and normal cat brain. After the infusion of [U-(14)C]-glucose, the incorporation of (14)C to free glutamic acid and aspartic acid of the brain was higher in the brain under subacute compression than in normal brain, i.e. the relative specific activity (RSA) was higher in the former than in normal brain. This tendency was more marked in aspartic acid. In observing the glucose metabolism by injecting Nembutal into carotid artery during the brain parfusion, the metabolic pattern at this stage showed a pattern intermediate between that during the high functional state and the low functional state of the brain under perfusion. This resembles the metabolic rates of glutamic acid and aspartic acid of the normal cat brain under a slight anesthesia by the infusion method. Only in the case of aspartic acid the relative specific acitivity (RSA) in the brain during the infusion was considerably lower than RSA during brain perfusion under the influence of Nembutal. In the protein component amino acid metabolism of crude mitochondrial fractions. RSA of the protein component glutamic acid was higher under subacute compression state than RSA of normal brain. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 84 9-10 1972 標準潅流および血流障害時のアラニンの脳代謝 353 363 EN Tsuneo Suzuki By means of the brain perfusion slightly modified of the method by Geiger artificial blood with L-[U-(14)C]-alanine was perfused and circulatory disturbances was induced by such artificial decrease of brain blood flow. In this instance, alanine metabolism in the brain was compared with the metabolism observable during the standard brain perfusion. The results are briefly summarized as follows. 1) In the blood flow disturbing experiments where the blood flow was lowered by 43.0-60.0%. oxygen consumption, carbon dioxide formation and glucose uptake were markedly decreased, while the output of lactic acid from the brain was increased as compared with respective values in standard brain perfusion. 2) Despite the fact that there was no significant difference in the alanine concentration between the arterial and venous blood, there could be observed a significant decrease in the radioactivity of the venous blood when compared with that of arterial blood. This indicates clearly that alanine is being exchanged between the blood and brain. In addition, it has been demonstrated that the radioactivity of blood in the blood flow disturbing experiments was 3.8±1.10% as against 5.90±1.80% in the experiments of standard brain perfusion. 3) About 0.42-0.33% alanine in the blood was taken up and it was oxidized completely to carbon dioxide by the brain, showing no significant difference between the standard perfusion and blood flow disturbing experiment. 4) In the case of blood flow disturbing experiments there were observed a marked increase of lactic acid and an increasing tendency of alanine in the brain. 5) In both the standard brain perfusion and blood flow disturbing experiment alanine taken up by the brain within 70 minutes contained 50% of (14)C in the brain. In the latter experiments the rate of (14)C-incorporation into glutamic acid, aspartic acid and glutamine was decreased and its incorporation into lactic acid was increased. 6) In the blood flow disturbing experiment radioactivity in glutamic acid, aspartic acid, glutamine, alanine and lactic acid in the brain tended to decrease. The radioactivity of GABA was greater than that of glutamic acid, there could be observed a glutamic acid-GABA compartmentation phenomenon. just as in the experiments with [U-(14)C] glucose in the perfused blood. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 81 5-6 1969 グルタミン酸系酸性アミノ酸の灌流脳機能に対する作用 411 427 EN Takayuki Hoaki By means of brain perfusion method, for the purpose to study the effects of glutamic acid and its related amino acids on EEG, cerebral blood flow and systemic blood pressures, these amino acids were administered into the carotid system of perfused cat brains under a certain fixed condition and the intensity of each drug action was compared. The amino acids tested in the experiments were L-glutamic acid, L-aspartic acid, N-methyl-D-aspartic acid, N-acetyl-DL-aspartic acid, β-hydroxy-glutamic acid, L-glutamic acid-Na, L-aspartic acid-Na, and N-acetyl-DL-aspartic acid-Ca. For EEG, acidic amino acids induce transient excitatory changes followed by inhibition. These excitatory changes prove to be low-amplitude fast waves or burst of seizures, and postexcitatory inhibition to be slow waves or flat waves. N-methyl-D-aspartic acid, even in a minimal dose, induces marked bursts of seizures followed by L-glutamic acid, L-aspartic acid, L-glutamic acid-Na, and L-aspartic acid-Na, in their potency. Generally, N-acetyl-DL-aspartic acids show only low-amplitude fast waves but some of them do induce burst of seizures. β-Hydroxy-glutamic acid elicits only low-amplitude fast waves but never burst of seizures. N-Acetyl-DL-aspartic acid-Ca, differing from the free form, never induces excitatory changes. For the cerebral blood flow, acidic amino acids decrease the blood flow, but those that show a strong decreasing effect are N-alkyl amino acids such as N-methyl-D-aspartic acid and N-acetyl-DL-aspartic acid. On the Other hand, acidic amino acids increase the systemic blood pressure, and of them such an effect is especially marked with N-alkyl amino acid. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 88 9-10 1976 フェニールケトン尿症に対するインスリンの効果第二編血中遊離アミノ酸に対する影響 709 716 EN Misako Okita 1. 対照正常人6例とPKU患者6例について,インスリン投与前と投与120分後の血中遊離アミノ酸の変化を検討した. 2. 対照正常人では, Aspが2例で増加したほかはすべてのアミノ酸が減少し, Met, Leu, Arg, Ileの順に減少率が大であった. 3. PKU患者では, Pheは4例, Tyrは全例で減少した. 4. PKU患者でGlu, Asp, Arg, His, Tau, Trp, Orn, Proの増加例があった. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 90 11-12 1978 実験的高アルギニン血症ウサギに関する研究第2編アルギニン大量負荷ウサギ尿中のguanidinosuccinic acidについて 1393 1398 EN Sadayoshi Suwaki Authentic guanidinosuccinic acid was converted into dimethylpyrimidyl derivative by reaction with acetylacetone, the carboxyl group was esterified by butylalcohol, and this derivative was analysed by the GC/MS technique. Then guanidinosuccinic acid was identified in urine of arginine loaded rabbit by means of selected ion recording. On the other hand, aspartic acid and isomolar of arginine was loaded simultaneously to rabbit, and a higher level of guanidinosuccinic acid was detected in the urine of 2 or 3 days and one week after. This fact suggest that guanidinosuccinic acid could be produced by transamidination of aspartic acid, receiving amidine group of arginine. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 90 7-8 1978 マウス腹水肉腫細胞核からの高分子量酸可溶性蛋白質の精製とその性質 999 1013 EN Kimiko Tsutsui A high molecular weight acid soluble nuclear protein (HAN-1) was isolated in a electrophoretically homogeneous state from mouse ascites sarcoma cells (SR-C3H cells) by the exclusion chromatography in Sephacryl S-200 and the DEAE-Sephadex chromatography of the nuclear 0.2M H(2)SO(4) extract. The content of HAN-1 in SR-C3H nuclei was about 4.3% per total histone, the highest among the cell types tested. The molecular weight of HAN-1 was estimated to be 125,000 by SDS-polyacrylamide gel electrophoresis. The amino acid composition of HAN-1 was rich in glutamic acid, alanine, lysine and aspartic acid, the acidic/basic amino acid ratio 1.8. The in vitro RNA synthesizing activity of SR-C3H cell RNA polymerases Ⅰ and Ⅱ on a naked DNA template was differentially affected by HAN-1; the reaction with polymerase I was inhibited and that with polymerase Ⅱ stimulated. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 90 1-2 1978 L-asparaginaseによるラツト血液および脳中の遊離アミノ酸とNH(3)の変化 159 165 EN T. Shohmori T. Kaneyuki T. Doi K. Mitani M. Kohsaka The enzyme L-asparaginase, which catalyzes the hydrolysis of the amino acids L-asparagine and L-glutamine to aspartic acid, glutamic acid and ammonia, is useful in the treatment of patients with acute leukemia. However, acute and delayed cerebral dysfunction often occurs in leukemic patients treated by L-asparaginase. Large amounts of L-aspartic acid, L-glutamic acid and ammonia may be liberated by the enzymatic action of L-asparaginase on its substrates L-asparagine and L-glutamine. The ensuing amino acid depletion or its excess may affect brain metabolism and lead to clinical abnormalities. The present paper reports on free amino acid levels and ammonia content in rat serum and cerebral cortex after L-asparaginase administration. Wistar male rats were used throughout this investigation. The acute experimental animals were administered 0.2ml of normal saline containing L-asparaginase (about 500 I.U./Kg B.W.) intraperitoneally and the acute control animals were given 0.2ml of normal saline intraperitoneally. 24h after this single administration, all rats were decapitated, and blood and cortex were collected for the estimation of free amino acids and ammonia. The acute L-asparaginase group showed some significant differences in serum compared to the control group. The most remarkable finding was the absence of asparagine. Aspartic acid and ammonia were elevated significantly; valine and methionine decreased significantly. In the cerebral cortex, aspartic acid and ammonia showed an insignificant change, but some other amino acids serine, glutamine, glycine, GABA and l-methylhistidine were significantly elevated. The chronic experimental group received 0.2ml of saline containing L-asparaginase (about 500 I.U./Kg B.W.) intraperitoneally once a day for 7 consecutive days. The chronic control group received 0.2ml of saline intraperitoneally in the same regime with the experimental group. All rats were fed a ground commercial diet and water ad libitum. The animals were housed in two large cages (the control cage and the experimental cage) in a dark-light room with alernating 12h dark-light cycles. Twenty-four hours after the last administration, all rats were decapitated for collection of blood and cerebral cortex. The chronic L-asparaginase group showed the absence of asparagine and significant increase of aspartic acid in serum similar to the acute L-asparaginase group but an insignificant increase of ammonia in blood. In addition to this finding, threonine, serine, glutamic acid and glycine were elevated significantly. In the cerebral cortex of the chronic L-asparaginase-treated animals, threonine, glycine and l-methylhistidine were significantly elevated compared to the control. It will be difficult to infer from our present data that the cerebral dysfunction induced by L-asparaginase may be correlated mainly with increased levels of aspartic acid, glutamic acid and ammonia in the cerebral cortex. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 99 11-12 1987 E1マウス脳内遊離アミノ酸のけいれん準備性獲得及びけいれんに伴う局所的変動に関する研究 1517 1528 EN Shigeo Suzuki Inbred mutant El mice are highly susceptible to convulsive seizures upon stimulation by "throwing". Amino acid levels were analyzed in the cortex, hippocampus, midrain, hypothalamus, pons-medulla oblongata and cerebellum of non-stimulated El mice [El(-)], of stimulated El mice [El(+)] during the interictal period and ddY mice (ddY) (controls) using an amino acid analyzer. Levels of aspartate, glutamate, glutamine and taurine were generally higher in the brains of E1 mice than those of ddY mice. Levels of aspartate, glutamate and GABA were lower in the brains of El(+) mice than those of El(-) mice. No significant difference was found in the hypothalamus. In addition, changes in amino acid levels were examined during the pre-convulsive stage, during convulsions and after convulsions of El(+) mice. The glutamate level was generally increased during the pre-convulsive stage, but other amino acids such as aspartate, glutamine, GABA and tauirne were decreased at that time compared to the interictal levels. These changes in amino acids were mostly found in the cortex, hippocampus and midbrain. These results suggest that glutamate may play a role in the triggering of seizures in El mice. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 100 5-6 1988 グアニジノコハク酸生合成経路に関する実験的研究 599 608 EN Rikiya Matsuda In order to understand the metabolic abnormalities occurring with renal failure, the biosynthetic pathway of guanidinosuccinic acid (GSA) was investigated in normal rat liver, because GSA is known as a uremic toxin and its synthetic pathway is unclear.After fresh liver was homogenized and centrifuged for 60 min at 100,000×g, the supernatant was fractionated by precipitation with ammonium sulfate. It was found that the activity of GSA biosynthetic enzymes was highest in the fraction between 30% and 40% saturation of ammonium sulfate. The reaction mixture contained potassium phosphate buffer (pH7.4), aspartate, urea, ATP and an ATP-generating system, MnCl(2), and enzyme solution. The optimum pH was 7.4. The activity was strongly accelerated by Mn(++) and Cu(++), while it was completely inhibited by Fe(++). Hydroxyurea, L-canaline, L-canavanine, and L-arginine could not substitute for urea.These results suggest that GSA is not formed by the transamidination of arginine to aspartate as proposed by Cohen, or by way of the guanidine cycles proposed by Natelson. It is possible that GSA is mainly synthesized from urea and aspartate directly in rat liver. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 78 2-3 1966 超低体温法の研究特に大脳皮質遊離γ-アミノ酪酸,グルタミン酸,アスパラギン酸について 235 257 EN Shuji Seki Effects of profound hypothermia on free amino acids in the cerebral cortex, especially on γ-aminobutyric acid, glutamic acid and aspartic acid, which have been believed to have intimate relationship to the cerebral function and metabolism, were studied in this report. Furthermore, effects of cytochrom C, pyridoxal phosphate and adenosine triphosphate on them in profound hypothermia were also investigated. Until 25°C, γ-aminobutyric acid and glutamic acid were decreased, whereas aspartic acid was almost constant. At 20°C γ-aminobutyric acid and aspartic acid were increased, on the other hand glutamic acid was constant. In the control group, in which respiration was not artificially maintained, γ-aminobutyric acid and glutamic acid were increased below 15°C and 10°C, respectively, while aspartic acid was almost constant. In the group, in which respiration was artificially continued after respiratory arrest (respired group), patterns of alterations in the free amino acids were different between normothermia to 25°C, 25°C to 20°C, 20°C to 15°C and 15°C to 10°C. Among them, the alteration between 25 to 20°C and 20 to 15°C seemed to be most prominent. Below 20°C, amounts of the 3 amino acids in the respired group were less than those in the control group. Amounts of the 3 amino acids in the respired group during cooling were more than those in the rewarmed group, except that of γ-aminobutyric acid in the rewarmed group at 25-30°C, which means that recovery of amino acid content from hypothermia was started after that of γ-aminobutyric acid. In the rewarmed group there was no difference in amino acid content between the group in which cardiac action and respiration were not resuscitated and the group in which only cardiac action was resuscitated, while there were prominent differences between the group in which only cardiac action was resuscitated and the group in which both cardiac action and respiration were resuscitated. Namely amounts of glutamic acid and aspartic acid in the former were more than those in the latter, but the difference of aspartic acid in both groups was statistically significant, but actually indefinite. In the rewarmed group resuscitation of respiration prevented further increase of glutamic acid and accelerated decrease of aspartic acid. There was no relationship to resuscitation of the heart. Cytochrom C delayed hypothermic change of γ-aminobutyric acid about 5°C and made hypothermic alterations of the other 2 amino acids less prominent. Pyridoxal phosphate and adenosine triphosphate alleviated hypothermic alterations in the 3 amino acids. On the results mentioned above, it was concluded that amounts of free γ-aminobutyric acid, glutamic acid and aspartic acid changed intimately with alterations of brain temperature, i.e. body temperature. Cytochrom C, pyridoxal phosphate and adenosine triphosphate alleviated hypothermic changes in the 3 amino acids. 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 4 1991 ラット脳内 σ 受容体の薬理学的特異性に関する研究―とくに抗精神病薬との抗虚血剤の作用について― 281 292 EN Yoshifumi Zushi Pharmacological specificity of several classes of drugs such as antipsychotics and antiischemic agents was assessed for σ receptors labeled with [(3)H] haloperidol. Specific binding of [(3)H] haloperidol in the presence of 25 nM spiperone was saturable and high affinity )Kd=1.96±1.31 nM, Bmax=2.37±0.27pmol/mg of protein;n=8). Among the 29 antipsychotics tested in inhibition studies, bromperidol and haloperidol were the most potent inhibitors (Ki=0.9nM, 1.0nM, respectively). The conventional antipsychotics moperone, timiperone etc. and the novel promising drugs YM-09151, Y-516, BMY-14802 and remoxipride potently inhibited [(3)H] haloperidol binding with the Ki in the range of low to moderate nanomolar. On the other hand, among the other 27 drugs tested, the antispasmodics eperisone and tolperisone, the antiischemic agents ifenprodil, the Ca(2+) antagonist flunarizine and cinnarizine, and the antitussives carbetapentane, cloperastine and dextromethorphan, were especially potent inhibitors. These results, taken together with the evidence that the antiischemic agents ifenprodil and dextromethorphan antagozine NMDA responses and NMDA receptor complex is a possible site of action for neuroprotective agents, strongly suggest that σ receptors may be potential sites of action for antiischemic as well as antipsychotic drugs, i.e., σ receptors mediate the neuroprotective effects of certain antiischemic agents by affecting the NMDA receptor complex. 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 完全全脳虚血後の脳障害に対するへパリン・ウロキナーゼ併用療法の効果に関する実験的研究 173 181 EN Naoki Morimoto The effect of heparin-urokinase (H-U) on the prevention of brain damage induced by ischemia was evaluated in 31 dogs subjected to an 18 min of complete global brain ischemia. Complete brain ischemia was produced by clamping the ascending aorta with aorto-atrial and aorto-femoral bypass formation. Post-ischemic cerebral blood flow (CBF) and other hemodynamic parameters were measured for 7 hours after ischemia in 15 dogs (acute study). Neurologic outcome was evaluated for 7 days after ischemia in 16 dogs (chronic study). Fifteen minutes after restoration of circulation to the brain, an intravenous bolus of heparin 100 I.U./kg and urokinase 3000 I.U./kg, was given, followed by continuous intravenous infusion of heparin 0.25 I.U./kg/min and urokinase 8.3 I.U./kg/min for 6 hours. H-U significantly improved both post-ischemic CBF and neurologic outcome. H-U was effective in treating brain damage when given 15 min after ischemia. These results suggest that H-U improved both post ischemic CBF and neurologic outcome owing to amelioration of the deterioration of microcirculation. 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 104 3-4 1992 カイニン酸, キスカル酸およびその拮抗薬投与にともなう脳波および線条体モノアミン代謝産物の変動 221 234 EN Masatsune Yamamoto The CNS action of kanie acid (KA), quisqualic acid (QA) and 1-(4-chlorobenzoyl)-piperazine-2, 3-dicarboxylic acid (pCB-PzDA) was investigated in male Sprague Dawley rats, and their effects on monoamina metabolite levels in rat striatum were studied using brain dialysis. Intracerebroventricularly injected KA and QA (100nmol) induced spike discharges, and pCB-PzDA (100nmol) suppressed electrocorticograms (ECoG) for 1 hour. pCB-PzDA aggravated KA induced spike discharges and inhibited QA-induced spike discharges. Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels increased transitorily by injection of 100nmol and continuously by injection of 100nmol of KA. KA increased the 5-hydroxyindoleachtic acid (5-HIAA) level 2 hours after the administration dose-dependently. Though 10nmol of QA increased the HVA level slightly, 100nmol of QA increased the DOPAC, HVA and 5-HIAA levels. Though 100nmol of pCB-PzDA increased the DOPAC and HVA levels, it inhibited the increases in DOPAC, HVA and 5-HIAA levels induced by KA. On the other hand,pCB-PzDA inhibited the increases in DOPAC, HVA and 5-HIAA levels induced by QA for 1 hour, after which the DOPAC and HVA levels increased additively. These finding suggest that pCB-PzDA acts not only as a non-NMDA antagonist but also on dopaminergic neurons directly. 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 105 1-2 1993 完全全脳虚血後の脳障害に対する炭酸リチウムの効果に関する研究 205 216 EN Yutaka Yaida The efficacy of lithium carbonate (Li) in preventing ischemic brain injury was evaluated in 36 dogs in a vegetative state. The dogs were subjected to 18 minutes of complete global brain ischemia and diveded into the following three groups ; control group (n=12), L-Ⅰ group (n=12), and L-Ⅱ group (n=12). In the L-Ⅰand L-Ⅱgroups, dogs were administered Li (10mg/kg) immediately after the end of ischemia (post-treatment). Only in the L-Ⅱ group, dogs were administered Li (100mg/kg) orally one day before the ischemic insult (pre-treatment). In each group, nuerologic outcome was evaluated for seven days after ischemia, and morphological changes in hippocampal CA1 pyramidal cells, small to medium-sized striatal neurons and cerebellar Purkinje cells were evaluated at day seven. In the L-Ⅱ group, neutrologic outcome was significantly better than that in the control group, and morphological improvement was recognized. Pre-treatment with Li might improve both neurologic and morphologic outcomes due to powerful inhibition of the stimulated phosphoinositide turnover during ishchemia. These fingings suggest that the stimulated phosphoinositide turnover during and immediately after ischemia might play an important role in brain injury induced by 18 minutes of complete global brain ischemia. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 106 1-2 1994 E1マウスの海馬におけるグルタミン酸,γ-アミノ酪酸及び glial fibrillary acidic protein の免疫組織化学的研究 103 115 EN Moon-Suk Suh Glutamic acid, γ-aminobutyric acid and glial fibrillary accidic protenin positive cells in the hippocampus of E1 mice and ddY mice were examined immunohistochemically. The shape of glutamic acid positive cells in CA1, CA2, CA3 and CA4 of hippocampus were expanded compar-ed to that of ddY mice. There was a space between cells and cells containing glutamic acid and the nucleus of such cells was larger in the CA1 of E1 mice than that of ddY mice. The glutamic acid cells were irregular and the nucleus was larger in the gyrus dentantus of E1 mice than that of ddY mice. There was an intermittence in the process of glutamic acid cells in the area of of str. radiatum of E1 mice. γ-Aminobutyric acid-posititve cells seemed to be expanded in CA1 of CA2, CA3, and CA4 and gyrus dentatus and there was space between such cells in the CA1 of E1 mice. Large γ-aminobutyric acid positive cells, which were located close to the gyrus dentatus in ddY mice, were not found in E1 mice. The number of γ-aminobutyric acid-positive cells was lower in E1 mice than in ddY mice. A greater number of glial fibrillary acidic protein postive cells was found in the area of the hippocampus in E1 mice than in ddY mice. These results suggest that E1 mice are genetically epileptic mice. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 107 7-8 1995 アデノシン関連物質による外傷性てんかん発症予防に関する研究 131 141 EN Junji Toma As oxidation of neural membranes by reactive oxygen species (ROS), especially hydroxyl radicals (・OH), is involved in the biochemical pathogenesis of post-traumatic epilepsy, post-traumatic epilepsy is thought to be prevented by treatment with ROS scavengers. In the present study, I first examined the effects of adenosine (Ado), 2-chloroadenosine (CI-Ado) and guanosine on ・OH and superoxide anion (O(-)(2)), generated by the Fenton reagent and the hypoxanthine-xanthine oxidase system, respectively, using electron spin resonance spectrometry. I also examined the effecta of Ado and Cl-Ado on the occurrence of epileptic discharges on the electrocorticogram (ECoG) induced by FeCl(3) injection (500nmol) into the sensorimotor cortex of rats, i.e., a model of an experimental post-traumatic epilepsy. Although O(-)(2) was not scavenged, ・OH were scavenged by Ado and Cl-Ado dose-dependently. The scavenging activity of Ado was 4 times stronger then thst of Cl-Ado. On the ECoG of rats given FeCl(3), sporadic spike discharges, polyspikes and/or ictal patterns started to be observed 15-90 min after the injection. Epileptic discharges did not appear or their occurrence was delayed by the intraperitioneal injection of Ado (5mg/kg) or Cl-Ado (1mg/kg) 30 min prior to the FeCl(3) injection, although Cl-Ado showed a chronotropic action. Thus Ado and Ci-Ado may be useful in the prevention and the attenuation of progression of post-traumatic epilepsy by scavenging ・OH and by their anticonvulsant effect. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 107 7-8 1995 拘束スレレスのラット脳内フリーラジカル, スーパーオキシドジスムターゼ活性およびチオバルビツール酸反応物質への影響に関する研究 91 98 EN Youko Okamura Immobilization stress for 6 hours induced hemorrhagic erosion in the rat stomach. Hydroxyl radicals singnificantly increased in the pons-medulla oblongata in stressed rats. Mitochondrial superoxide dismutase (SOD) activity was enhanced in the midbrain but was lowered in the cortex, hippocampus and cerebellum in stressed rats. Thiobarbituric acid reactive substances increased by stress in the cortex and midbrain. These finding suggested that immobilization stress generated hydroxyl radicals and accelerated lipid peroxidation, and affected mitocho-drial SOD activity which may lead to neuronal damage in stressed rats. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 107 7-8 1995 改良型神経伝達物質放出測定装置によるE1マウス海馬切片よりの神経伝達物質放出と抗てんかん薬ゾニサミドの影響に関する研究 69 78 EN Atsushi Endo Using an experimental apparatus for estimating neurotransmitter release from brain slices, which involved an improved type of perfusion chamber and more well-controlled tube lines than the previous one were aspartic acid and γ-aminobutyric acid (GABA) release from hippocampal slices from epileptic E1 mice estimated more exactly and stably. Zonisamide had no effect on the aspartic acid release from hippocampal slices of E1 mice by zonisamide. However, zonisamide accelerated dose dependently GABA release from hippocampal slices of non-stimulated E1 mice, though no such acceleration was observed in stimulated E1 mice, i. e., repeatedly convulsed E1 mice. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 00301558 119 2 2007 統合失調症の分子病態研究について - 遺伝子研究を中心に - 119 125 EN Yukitaka Morita Hiroshi Ujike Shigetoshi Kuroda No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2007 Effect of amodiaquine, a histamine N-methyltransferase inhibitor, on Propionibacterium acnes and lipopolysaccharide-induced hepatitis in mice EN Akira Yokoyama We examined whether treatment with amodiaquine, a potent inhibitor of histamine N-methyltransferase protects mice from Propionibacterium acnes (P. acnes)-primed and lipopolysaccharide (LPS)-induced hepatitis. The subcutaneous injection of amodiaquine (2 and 5 mg/kg) significantly increased the histamine levels in the liver in comparison to saline treated mice. Pretreatment with amodiaquine also improved the survival rate of the hepatitis mice, and this improvement was partially associated with the decrease in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Amodiaquine partially suppressed increases of tumor necrosis factor (TNF)-alpha in the serum and TNF-alpha mRNA expression in the liver, whereas the expression of interleukin (IL)-18, interferon (IFN)-gamma and IL-12 in the liver was not changed by amodiaquine treatment. In conclusion, the present findings suggested that the elevation of endogenous histamine by amodiaquine may thus play a protective role through the regulation of TNF-alpha production in endotoxin-induced hepatic injury mice. No potential conflict of interest relevant to this article was reported.

岡山大学環境理工学部 Acta Medica Okayama 1341-9099 11 1 2006 ポリアスパラギン酸系温度応答性ゲルの創製 103 106 EN Hiroki Uehara Fumiaki Tanimoto Yoshiro Kitamura Hidekazu Yoshizawa 10.18926/fest/11444 Recently, thermo-responsive polymer gels have been studied in various research fields such as drug delivery system. One of represetative thermo-responsive polymer gels is poly(N-isopropylacrylamide) gel (PNIPAAm) that has a rapid and reversible volume phase transition. However, PNIPAAm is not biodegradable, resulting in limitation of its use in medical fields. Novel thermo-responsive polymer gel was prepared by closslinking of isopropylamine modified poly(succinimide) (IPA-PSI) (Poly[α,β -(DL-aspartate isopropyl amide)-co-(succinimide)]) with hexamethylenediamine. Because of peptide bonds in backbone, therefore, it is expected to possess biodegradability and biocompatibility. These gels changed their volume in response to change of environment such as temperature, pH and concentration of salt in water. Crosslinkage density and substitution degree of IPA-PSI affected volume phase transition bahavior of the gel. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1991 Aspartic acid release from cerebral cortical slices of El mice with high seizure susceptibility EN No potential conflict of interest relevant to this article was reported.