The Journal of Medical Investigation
Online ISSN : 1349-6867
Print ISSN : 1343-1420
ISSN-L : 1343-1420
Volume 52 , Issue Supplement
Showing 1-22 articles out of 22 articles from the selected issue
Proceedings
  • Eiji Takeda
    2005 Volume 52 Issue Supplement Pages 223-224
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Severe and prolonged stress exposure impairs homeostatic mechanisms, particularly associated with the onset of depressive illness. The establishment of functional foods that correctly regulate stress response must be an important and new field for human nutrition. This exciting science has been vigorously achieving in the 21st century COE program of University of Tokushima Graduate School. J. Med. Invest. 52 Suppl.: 223-224, November, 2005
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  • Mari Tabuchi, Hideya Nagata, Masanori Nomura, Sawako Katsube, Akihiro ...
    2005 Volume 52 Issue Supplement Pages 225-227
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    The handing of the cells or tissues is essential for proteomics research or drug screening, where labor is not avoidable. The steps of cell wash, protein extraction, protein denaturing are complicated procedures in conventional method using centrifugation and pipetting in the laboratory. This is the bottle-neck for proteome research. To solve these problems, we propose to utilize the nanotechnology, which will improve the proteomics methodology. Utilizing the nanotechnology, we developed a novel microseparation system, where centrifugation and pipetting are needless. This system has a nanostructured microdevice, by which the cell handling, protein extraction, and antibody assay can be performed. Since cell transfer is needless, all cells are corrected without any loss during the cell-pretreatment procedures, which allowed high reproducibility and enabled the detection of low amount of protein expression. Utilizing the microdevice, we analyzed the stress induced proteins. We further succeeded the screening of food that was useful for immunity and found that an extraction from seaweed promoted the apoptosis of T-lymphoblastic cells. Here, we present an on-line microdevice for stress proteomics. J. Med. Invest. 52 Suppl.: 225-227, November, 2005
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  • Etsuo Niki, Yasukazu Yoshida
    2005 Volume 52 Issue Supplement Pages 228-230
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Biomarkers are essential for assessment of oxidative stress and evaluation of antioxidant capacity in vivo. Total hydroxyoctadecadienoic acid (HODE) and 7-hydroxycholesterol measured after reduction and saponification of biological fluids may be used as reliable biomarker. J. Med. Invest. 52 Suppl.: 228-230, November, 2005
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  • Christoph W Turck, Giuseppina Maccarrone, Eser Sayan-Ayata, Archana M ...
    2005 Volume 52 Issue Supplement Pages 231-235
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    The identification of disease markers in tissues and body fluids requires an extensive and thorough analysis of its protein constituents. In our efforts to identify biomarkers for affective and neurological disorders we are pursuing several different strategies. On one hand we are using animal models that represent defined phenotypes charactersistic for the respective disorder in humans. In addition, we are analyzing human specimens from carefully phenotyped patient groups. Several fractions representing different protein classes from human cerebrospinal fluid obtained by lumbar puncture are used for this purpose. Our biomarker identification efforts range from classical proteomics approaches such as two dimensional gel electrophoresis and mass spectrometry to phage display screens with cerebrospinal fluid antibodies. J. Med. Invest. 52 Suppl.: 231-235, November, 2005
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  • Atsuo Sekiyama, Haruyasu Ueda, Shin-ichiro Kashiwamura, Kensei Nishida ...
    2005 Volume 52 Issue Supplement Pages 236-239
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Psychological/physical stresses have been reported to exacerbate auto-immune and inflammatory diseases. To clarify a mechanism by which non-inflammatory stresses disrupt host defenses, responses to immobilization stress in mice were investigated, focusing on the role of a multifunctional cytokine, interleukin-18 (IL-18). In the adrenal cortex, the stress induced IL-18 precursor proteins (pro-IL-18) via ACTH and a superoxide-mediated caspase-1 activation pathway, resulting in conversion of pro-IL-18 to the mature form which was released into plasma. Inhibitors of caspase-1, reactive oxygen species and P38 MAPK prevented stress-induced accumulation of plasma IL-18. These inhibitors also blocked stress-induced IL-6 expression. This, together with the observation that IL-6 was not induced in stressed-IL-18 deficient mice, showed that IL-6 induction by stress is dependent on IL-18. In stressed organisms, IL-18 may influence pathological and physiological processes. Controlling the caspase-1 activating pathway to suppress IL-18 levels may provide preventative means against stress-related disruption of host defenses. J. Med. Invest. 52 Suppl.: 236-239, November, 2005
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  • Takashi Kinoshita, Zsolt Lepp, Hiroshi Chuman
    2005 Volume 52 Issue Supplement Pages 240-241
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Over the past several decades, thousands of natural organic compounds have been isolated from foods, and the information about their structures and biological activities has been accumulated. Despite the long research history of food products and their potential great promise as a medicine and functional food, the systematic research and development have not been carried out extensively. For understanding of the comprehensive structure-activity relationship, we have developed the database system of flavonoids, which are frequently found in vegetables and fruits. We also plan to execute a virtual screening of flavonoids with antidepressant activity by using the database and an advanced chemoinformatic tool. In this section, we will briefly describe (1) flavonoid database and (2) virtual screening of antidepressant compounds. J. Med. Invest. 52 Suppl.: 240-241, November, 2005
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  • Yutaka Nakaya, Yasuko Hata, Kaori Ishida, Akira Takahashi, Kyoko Morit ...
    2005 Volume 52 Issue Supplement Pages 242-243
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    DNA microarray was used to measure stress response by exercise in peripheral blood leukocytes. Aerobic exercise did not alter mRNA pattern or urinary secretion of 8-hydroxy-2’-deoxyguanosine (8-OHdG). Strenuous exercise increased urinary secretion of 8-OHdG and altered mRNA pattern in microarray. These results suggest that moderate exercise, i. e. aerobic exercise, did not show any change in 8-OHdG, an oxidative stress marker, or mRNA expression in the leukocytes, which might reflect whole body neurohormanal changes. In addition, strenuous exercise produced quite different expression pattern from those of psychological stress. J. Med. Invest. 52 Suppl.: 242-243, November, 2005
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  • Yutaka Nakaya, Masaki Morishima-Yamato, Kaori Ishida, Nagakatsu Harada ...
    2005 Volume 52 Issue Supplement Pages 244
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    A stress-resistant rat model was introduced. SPORTS (Spontaneously-Running-Tokushima-Shikoku) rats showed significantly shorter time of immobility in the forced swim test compared to control Wister rats. Increase norepinephrine concentration secondary to decreased activity of monoamine oxidase A (MAOA) in hippocampus was observed in this model rats. This model rats are considered to be useful for studying the mechanism of psychological stress. J. Med. Invest. 52 Suppl.: 244, November, 2005
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  • Mikiko Ito, Sakiko Haito, Mari Furumoto, Yoshichika Kawai, Junji Terao ...
    2005 Volume 52 Issue Supplement Pages 245-248
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Serotonin transporters (SERTs) are pre-synaptic proteins specialized for the clearance of serotonin following vesicular release at central nervous system (CNS) and enteric nervous system synapses. SERTs are high affinity targets in vivo for antidepressants such as serotonin selective reuptake inhibitors (SSRIs). These include ‘medical’ psychopharmacological agents such as analgesics and antihistamines, a plant extract called St John’s Wort (Hypericum). Osteoclasts are the primary cells responsible for bone resorption. They arise by the differentiation of osteoclast precursors of the monocyte/macrophage lineage. The expression of SERTs was increased in RANKL-induced osteoclast-like cells. Using RANKL stimulation of RAW264.7 cells as a model system for osteoclast differentiation, we studied the direct effects of food factor on serotonin uptake. The SSRIs (fluoxetine and fluvoxamine) inhibited markedly (-95%) in serotonin transport in differentiated osteoclast cells. The major components of St. John’s Wort, hyperforin and hypericine were significantly decreased in serotonin transport activity. Thus, a new in vitro model using RANKL-induced osteoclast-like cells may be useful to analyze the regulation of SERT by food factors and SSRIs. J. Med. Invest. 52 Suppl.: 245-248, November, 2005
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  • Mutsuko Shirai, Yoshichika Kawai, Rintaro Yamanishi, Junji Terao
    2005 Volume 52 Issue Supplement Pages 249-251
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Oxidative stress is frequently mentioned in relation to the neurodegenerative diseases. This study examined the effect of three herb extracts, Hypericum perforatum, Ginkgo biloba L. and Apocynum venetum L., and their components on lipid hydroperoxide-induced oxidative stress in PC-12 cells. Among them, the extract of Apocynum venetum and its components showed the remarkable inhibitory effect, indicating that this herb extract serves as a protective agent against lipid peroxidation-related oxidative stress in CNS. Oxidative stress may be associated with the progress of depression, as this extract has been proposed to be an effective antidepresant herb. J. Med. Invest. 52 Suppl.: 249-251, November, 2005
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  • Katherine L Tucker
    2005 Volume 52 Issue Supplement Pages 252-258
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Although health disparities are well documented among minority populations, they have not been fully explained by socio-economic status. We have demonstrated that Puerto Rican elders in Massachusetts are significantly more likely to have physical disability, depression, cognitive impairment, diabetes and other chronic health conditions than do non-Hispanic white elders living in the same neighborhoods. This suggests that the disparity is not due only to physical or neighborhood location, and that other factors must be influencing these differences. In that study, we also showed that the Puerto Rican elders had diets that were limited in diversity and were relatively low in micronutrient content. In our ongoing cohort study within our Boston Puerto Rican Center for Population Health and Health Disparities, we are investigating the relationships between psychosocial stress, its effect on physiologic burden or “allostatic load” and, in turn, how this is associated with the functional outcomes previously identified as areas of health disparity: depression, cognitive impairment and functional limitation. We further propose that the association between life stress, physiologic response and chronic conditions is modified by nutritional status, with a focus on B vitamins and antioxidant vitamins. J. Med. Invest. 52 Suppl.: 252-258, November, 2005
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  • Eiji Takeda, Hidekazu Arai, Hironori Yamamoto, Hisami Okumura, Yutaka ...
    2005 Volume 52 Issue Supplement Pages 259-265
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Repeated mental stress may lead to chronic alterations in cortisol and catecholamine concentrations and to insulin resistance. Furthermore, chronically elevated cortisol concentrations may favour the development of abdominal obesity and of the metabolic syndrome. Oxidative stress impairs glucose uptake in muscle and fat and correlates with BMI. Obese subjects with type 2 diabetes, especially soon after the onset of diabetes, usually exhibit postprandial hyperglycemia with delayed hyperinsulinemia. It is recognized that insulin resistance causes postprandial hyperglycemia; however, it is also possible that impairment of early insulin secretion in response to an oral glucose load is the reason why postprandial hyperglycemia occurs. Since even modest increases in postprandial glucose values can be a risk factor for cardiovascular disease. Therefore, the effects of palatinose based functional food which reduces postprandial hyperglycemia and hyperinsulinemia were investigated in rats. This novel food definitely reduced visceral fat accumulation and improved insulin sensitivity. Therefore, it is suggested that functional food which suppresses postprandial glucose level is beneficial for both stress and metabolic controls. J. Med. Invest. 52 Suppl.: 259-265, November, 2005
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  • Tetsuro Ohmori, Kyoko Morita, Toshiro Saito, Masayuki Ohta, Shu-ichi U ...
    2005 Volume 52 Issue Supplement Pages 266-271
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Precise assessment of stress is an imminent issue to deal with stress-related social, medical and psychological problems. Psychological stress is known to stimulate the neuroendocrine, sympathetic nervous, and immune systems. By analyzing mRNA expression levels in leukocytes, which express receptors for hormones, neurotransmitters, growth factors, cytokines, and other stress related signals, levels of stress may be adequately measured. In a series of studies, our group has developed a cDNA microarray specifically designed to measure the mRNA levels of stress-related genes in peripheral blood leukocytes. This microarray enabled us to sensitively detect the response to psychological stress. In addition, our preliminary study suggests that the array could differentiate patients with depression from sex- and age-matched control subjects. J. Med. Invest. 52 Suppl.: 266-271, November, 2005
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  • Kotaro Asanuma, Maren Carbon-Correll, David Eidelberg
    2005 Volume 52 Issue Supplement Pages 272-279
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Functional neuroimaging, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), provides a valuable technique for detecting regional changes in brain metabolic activity associated with human disease. These techniques have been applied in different dystonic disorders including primary generalized dystonia and dopa-responsive dystonia (DRD), as well as focal dystonic syndromes such as torticollis, writer’s cramp, and blepharospasm. A common finding is abnormality of the basal ganglia and associated outflow pathways to sensorimotor cortex and other regions involved with motor performance. Other recent imaging research has utilized diffusion-based MRI techniques to localize distinct microstructural abnormalities in dystonia patients and gene carriers. This presentation will focus on an integrated approach to understanding the pathophysiology of this genetic and biochemically diverse disorder. J. Med. Invest. 52 Suppl.: 272-279, November, 2005
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  • Ryuji Kaji, Satoshi Goto, Gen Tamiya, Satoshi Ando, Satoshi Makino, LV ...
    2005 Volume 52 Issue Supplement Pages 280-283
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Pathological findings in dystonia have been unclear. X-linked recessive dystonia-parkinsonism (XDP, DYT3), endemic in the Panay island, the Philippines, is characterized by the clinical onset with dystonia followed by parkinsonism. It provides a unique opportunity to explore the anatomical basis of dystonia, because it has discernible pathological changes even at its early phase of dystonia. After extensive searches for the anatomical basis in XDP, we found selective loss of striosomal neurons in the striatum in dystonic patients’ brain. Because striosomal neurons inhibit nigrostriatal dopaminergic neurons via GABAergic innervation, the striosomal lesion could account for dopamine excess in the striatum, which in turn causes a hyperkinetic state or dystonia. We also identified the causative gene as one of the general transcription factor genes, TAF1. XDP has certain similarities to Huntington disease not only in pathological and clinical findings, but also the molecular mechanism, which disturbs expression of genes essential for striatal neurons, such as DRD2. Therapeutic intervention may become possible through pharmacological measures that affect gene expression. J. Med. Invest. 52 Suppl.: 280-283, November, 2005
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  • Tsuyoshi Hirose, Tetsuro Kikuchi
    2005 Volume 52 Issue Supplement Pages 284-290
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    It is obvious that DA is an important neurotransmitter in vivo. It is involved in a variety of physiological processes such as mental processes, motor function and hormone regulation. In this context, it is quite understandable that a DA D2 receptor antagonist that inhibits the DA D2 receptor regardless of the state of activity of dopaminergic neurotransmission and inhibit the physiological function of DA can have a variety of adverse effects. In contrast to DA D2 antagonists, aripiprazole acts as an antagonist at the DA D2 receptor in the state of excessive dopaminergic neurotransmission, while it acts as an agonist at the DA D2 receptor in the state of low dopaminergic neurotransmission, and thus attempts to bring the state of dopaminergic neurotransmission to normal. This activity of aripiprazole to regulate dopaminergic neurotransmission is physiologically reasonable, and can be regarded as a stabilizing effect, for which aripiprazole is called a dopamine system stabilizer J. Med. Invest. 52 Suppl.: 284-290, November, 2005
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  • Takashi Kinoshita, Zsolt Lepp, Hiroshi Chuman
    2005 Volume 52 Issue Supplement Pages 291-292
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Flavonoids are polyphenolic compounds that exist ubiquitously in foods of plant origin. Flavonoids show various interesting biological activities, such as removal of oxygen radical, anti-cancer action, improvement of high blood pressure, antibacterial, antibiotic and anti-allergy actions. So far, over 4000 structurally unique flavonoids have been isolated from plant sources. Recently, databases of chemicals have been utilized in to help chemical and biological researches, however the comprehensive database of flavonoids with information about structural, biological and physicochemical properties not yet available. We have constructed the integrated database of flavonoids for nutrition research. J. Med. Invest. 52 Suppl.: 291-292, November, 2005
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  • Xiangli Liu, Hiroshi Chuman
    2005 Volume 52 Issue Supplement Pages 293-294
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Lipophilicity was evaluated by the high-throughput RP-HPLC method. A set of 40 solutes with well-defined solvatochromic parameters were selected in this study. The chromatographic results show that, under the conditions of study, the lipophilicity index log kw was highly correlated with the experimental log Poct. J. Med. Invest. 52 Suppl.: 293-294, November, 2005
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  • Kunitaka Nashiki, Yutaka Taketani, Emi Shuto, Rieko Tanaka, Ayako Tani ...
    2005 Volume 52 Issue Supplement Pages 295-296
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Oxidative stress has emerged as an important pathogenic factor in the development of long-term complications, such as hypertension, atherosclerosis, nephropathy, and cancer. Taking many antioxidants from natural food may be effective to prevent us from those diseases. We have attempted to evaluate the effect of improvement by dietary antioxidants on the endothelial dysfunction induced by hyperglycemia. Fluorescence indicators for reactive oxygen species and nitric oxide were employed to the evaluation. The combination of those fluorescence indicators could be powerful tool to evaluate the effect of anti-stress nutrients on both oxidative stress and endothelial dysfunction. J. Med. Invest. 52 Suppl.: 295-296, November, 2005
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  • Zsolt Lepp, Takashi Kinoshita, Hiroshi Chuman
    2005 Volume 52 Issue Supplement Pages 297-299
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Virtual screening was carried out against various biological targets related to depression by support vector machine classification using the atom-type descriptors. The models were effective as over 75 and 95% of the molecules in external test datasets could be correctly classified, depending on target. Antidepressant compounds had predicted activity against 2.3 targets, on average. An introduction is given to virtual screening and the results of classification experiments are presented J. Med. Invest. 52 Suppl.: 297-299, November, 2005
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  • Hiroyuki Sakakibara, Kaori Ishida, Yuki Izawa, Yuko Minami, Satomi Sai ...
    2005 Volume 52 Issue Supplement Pages 300-301
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    Chronic stress has been reported to be an essential factor for depression. In this study, the effect of forced swimming stress on neurotransmitters and cellular signaling pathway contributing to brain functions was investigated using the forced swimming test (FST) in order to understanding of mechanisms to regulate stress signals in brain. Antidepressant drug, imipramine, significantly reduced the immobility time of male rats in the FST by 85% at a dose of 15mg/kg for 2 weeks. This result indicated that the swimming stress caused a depressed state in the rats without administration of imipramine. Swimming stress significantly lowered the serotonergic ratio and also markedly enhanced the phosphorylation of ERK1/2 in the hypothalamus region compared to the rats without FST. These phenomena may be included in key mechanisms of the development of depression. J. Med. Invest. 52 Suppl.: 300-301, November, 2005
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  • Satsuki Sumitani, Tsunehiko Tanaka, Shin’Ya Tayoshi, Koshi Ota, ...
    2005 Volume 52 Issue Supplement Pages 302-303
    Published: 2005
    Released: December 13, 2005
    JOURNALS FREE ACCESS
    To investigate the brain activation in the prefrontal cortex (PFC) during mental works, we examined blood oxygenation changes of healthy subjects by using multi channel near infrared spectropcopy (NIRS). It was directly confirmed that the PFC was activated during mental tasks in vivo and it was suggested that distribution of the activation in the PFC is different among healthy individuals. J. Med. Invest. 52 Suppl.: 302-303, November, 2005
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