Himeji, Japan

Himeji Dokkyo University

Himeji, Japan

Himeji Dokkyo University is a private university in Himeji, Hyōgo, Japan. The predecessor of the school was founded in 1881, and it was chartered as a university in 1986.The first faculties were the Faculty of Foreign Languages, the Faculty of Law. In 1989, the faculty of Econo-informatics was founded, and in 2006 faculties of Medicine, Health and Physical Therapy were started.The Japanese foundation University Accreditation Association, according to a 2010 university evaluation and accreditation, has certified the university as being in conformity with Japanese university standards.On May 26, 2010, the decision was taken to stop accepting new student applications to the graduate law school, which was opened in April 2006. No students passed the entrance exam. Wikipedia.

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Sakita M.,Kyoto Tachibana University | Murakami S.,Himeji Dokkyo University | Fujino H.,Kobe University
BMC Neuroscience | Year: 2016

Background: Regression of myelinated peripheral nerve fibers in the lower extremities contributes to sarcopenia and balance dysfunction in normal aging. This subclinical regression of myelinated fibers (MFs) is heavily influenced by alterations in microvasculature, though the mechanism underlying these age-related degenerative phenomena remains unclear. The aim of the present study was to examine age-related regressions in myelinated distal peripheral nerve fibers as well as capillary architecture in rats using both morphological and histochemical methods. Results: MFs were categorized into tertiles of 'large', 'medium', and 'small' sizes based on the distribution of MF diameters. A two-way ANOVA was used to assess effects of fiber size (large/medium/small) and group (young/elderly) on myelin thickness, axon diameter, myelin perimeter, axon perimeter, and G-ratio (axon diameter/fiber diameter). Significant main effects were observed for both MF size and group with respect to all dimensions except for G-ratio. Values for fiber diameter (P < 0.01), myelin thickness (P < 0.01), axon diameter (P < 0.01), myelin perimeter (P < 0.01), and axon perimeter (P < 0.01) were significantly lower than those in the young group. Additionally, mean capillary diameter and number of microvascular branch points were significantly lower in the elderly group than in the young group. Conclusions: The present study demonstrated that spontaneous age-related regression predominantly occurs for all fiber sizes in the distal peripheral nerves and the capillary architecture. The results of the present study further suggest that both the distal MFs and capillaries in the peripheral nerve may simultaneously regress with aging. © 2016 The Author(s).

Koma H.,Himeji Dokkyo University | Yamamoto Y.,Himeji Dokkyo University | Nishii A.,Himeji Dokkyo University | Yagami T.,Himeji Dokkyo University
Neuropharmacology | Year: 2017

15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) induces neuronal cell death via apoptosis independently of its receptors. 15d-PGJ2 inhibits growth factor-induced cell proliferation of primary astrocytes via down-regulating phosphoinositide 3-kinase (PI3K)-Akt pathway. Although 15d-PGJ2-reduced cell viability is accompanied with attenuation of the PI3K signaling in neuroblastoma, it has not been sufficiently clarified how 15d-PGJ2 induces cell death in primary neurons. Here, we found that 15d-PGJ2 exhibited neurotoxicity via inhibiting the PI3K signaling in the primary culture of rat cortical neurons. A PI3K inhibitor induced neuronal cell death regardless serum throughout maturation, confirming that PI3K is required for neuronal cell survival. The inhibitor disrupted neuronal cell bodies, shortened neurites thinly, damaged plasma membranes and activated caspase-3 similarly to 15d-PGJ2. Little additive or synergistic neurotoxicity was detected between 15d-PGJ2 and the PI3K inhibitor. A PI3K activator prevented neurons from undergoing the 15d-PGJ2-induced cell death in vitro. In vivo, the PI3K signaling is required for contextual memory retrieval, which was impaired by bilateral injection of 15d-PGJ2 into hippocampus. The activator suppressed the 15d-PGJ2-impaired memory retrieval significantly. In neurons as well as primary astrocytes and neuroblastomas, 15d-PGJ2 exhibited cytotoxicity via suppressing the PI3K-Akt pathway in vivo and in vitro. © 2016 Elsevier Ltd

Adverse experiences in early life profoundly influence the developing nervous, endocrine, and immune systems, and also affect human behaviour during adult life and are considered in the pathogenesis of psychiatric disorders. Numerous studies have provided evidence that maternal deprivation in the middle of a stress hyporesponsive period (SHRP) causes multiple behavioural and physiological abnormalities that mimic positive symptoms of schizophrenia in humans. To investigate the neurochemical characteristics of maternal deprivation in the middle of the SHRP in the context of a possible animal model of the symptoms of schizophrenia, we examined calcineurin expression in the hippocampus of maternally deprived rats. To investigate other behavioural characteristics, we behaviourally phenotyped the rats by applying a comprehensive behavioural test battery. The results indicate that maternal deprivation in the middle of the SHRP has no effects on general health, neurological reflexes, sensory function, or motor function, but does have sex-specific effects on a type of anxiety-related behaviour in the open field test and male-specific effects on hippocampal calcineurin expression, social behaviour, and objective memory function. An interpretation of our results and previous studies in the context of the neurodevelopmental hypothesis of schizophrenia suggests that maternal deprivation in the middle of the SHRP in rats models some positive and negative aspects of schizophrenia. The findings regarding the sex-specific effects of maternal deprivation in the middle of the SHRP may become a strong tool for investigating sex differences in the pathogenesis and pathology of schizophrenia in humans. © 2012 Elsevier B.V.

Yagami T.,Himeji Dokkyo University | Koma H.,Himeji Dokkyo University | Yamamoto Y.,Himeji Dokkyo University
Molecular Neurobiology | Year: 2016

Cyclooxygenases (COXs) oxidize arachidonic acid to prostaglandin (PG) G2 and H2 followed by PG synthases that generates PGs and thromboxane (TX) A2. COXs are divided into COX-1 and COX-2. In the central nervous system, COX-1 is constitutively expressed in neurons, astrocytes, and microglial cells. COX-2 is upregulated in these cells under pathophysiological conditions. In hippocampal long-term potentiation, COX-2, PGE synthase, and PGE2 are induced in post-synaptic neurons. PGE2 acts pre-synaptic EP2 receptor, generates cAMP, stimulates protein kinase A, modulates voltage-dependent calcium channel, facilitates glutamatergic synaptic transmission, and potentiates long-term plasticity. PGD2, PGE2, and PGI2 exhibit neuroprotective effects via Gs-coupled DP1, EP2/EP4, and IP receptors, respectively. COX-2, PGD2, PGE2, PGF2α, and TXA2 are elevated in stroke. COX-2 inhibitors exhibit neuroprotective effects in vivo and in vitro models of stroke, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, and schizophrenia, suggesting neurotoxicities of COX products. PGE2, PGF2α, and TXA2 can contribute to the neurodegeneration via EP1, FP, and TP receptors, respectively, which are coupled with Gq, stimulate phospholipase C and cleave phosphatidylinositol diphosphate to produce inositol triphosphate and diacylglycerol. Inositol triphosphate binds to inositol triphosphate receptor in endoplasmic reticulum, releases calcium, and results in increasing intracellular calcium concentrations. Diacylglycerol activates calcium-dependent protein kinases. PGE2 disrupts Ca2+ homeostasis by impairing Na+-Ca2+ exchange via EP1, resulting in the excess Ca2+ accumulation. Neither PGE2, PGF2α, nor TXA2 causes neuronal cell death by itself, suggesting that they might enhance the ischemia-induced neurodegeneration. Alternatively, PGE2 is non-enzymatically dehydrated to a cyclopentenone PGA2, which induces neuronal cell death. Although PGD2 induces neuronal apoptosis after a lag time, neither DP1 nor DP2 is involved in the neurotoxicity. As well as PGE2, PGD2 is non-enzymatically dehydrated to a cyclopentenone 15-deoxy-Δ12,14-PGJ2, which induces neuronal apoptosis without a lag time. However, neurotoxicities of these cyclopentenones are independent of their receptors. The COX-2 inhibitor inhibits both the anchorage-dependent and anchorage-independent growth of glioma cell lines regardless of COX-2 expression, suggesting that some COX-2-independent mechanisms underlie the antineoplastic effect of the inhibitor. PGE2 attenuates this antineoplastic effect, suggesting that the predominant mechanism is COX-dependent. COX-2 or EP1 inhibitors show anti-neoplastic effects. Thus, our review presents evidences for pathophysiological roles of cyclooxygenases and prostaglandins in the central nervous system. © 2015, Springer Science+Business Media New York.

Hirose M.,Hyogo College of Medicine | Kuroda Y.,Himeji Dokkyo University | Murata E.,University of Fukui
Pain Practice | Year: 2016

Nerve growth factor (NGF) was first discovered approximately 60 years ago by Rita Levi-Montalcini as a protein that induces the growth of nerves. It is now known that NGF is also associated with Alzheimer's disease and intractable pain, and hence, it, along with its high-affinity receptor, tropomyosin receptor kinase (Trk) A, is considered to be 1 of the new targets for therapies being developed to treat these diseases. Anti-NGF antibody and TrkA inhibitors are known drugs that suppress NGF/TrkA signaling, and many drugs of these classes have been developed thus far. Interestingly, local anesthetics also possess TrkA inhibitory effects. This manuscript describes the development of an analgesic that suppresses NGF/TrkA signaling, which is anticipated to be 1 of the new methods to treat intractable pain. © 2016 World Institute of Pain.

Takano M.,Kobe Gakuin University | Matsuyama S.,Himeji Dokkyo University
European Journal of Pharmacology | Year: 2014

Bradykinin is a vasoactive peptide that participates in numerous inflammatory processes, vasodilation, and cell growth/survival; it mainly acts through two receptor subtypes, bradykinin B1 and bradykinin B 2 receptors, which are G protein-coupled receptor (GPCR) family members. Details on ubiquitin-dependent degradation via the lysosome and/or proteasome, and the recycling process that directs bradykinin B2 receptor to the cell surface after agonist-induced endocytosis remain unclear; nevertheless, intracellular localization and internalization of GPCRs following stimulation by ligands are well known. Evidence concerning the nuclear localization and functions of GPCRs has been accumulating. The bradykinin B 2 receptor has been shown to localize in the nucleus and suggested to function as a transcriptional regulator of specific genes. The transfer of membrane GPCRs (regardless of liganding), including the bradykinin B2 receptor to the nucleus can be attributed to the presence of a peptide sequence referred to as the nuclear localization signal (NLS). More recently, we found that nuclear bradykinin B2 receptors form heterodimers with the nuclear lamina protein, lamin C. The function of heterodimerization of the bradykinin B2 receptor with lamin C is still unclear. However, nuclear proteins lamin A/C are involved in a variety of diseases. Although further studies are required to elucidate the precise functions and mechanisms of intracellular and nuclear bradykinin B2 receptors, here we discuss the role of lamin A/C in laminopathies and examine the clinical significance of the bradykinin B2 receptor heterodimer. © 2014 Elsevier B.V.

Miyamoto K.,Himeji Dokkyo University
Journal of Peptide Science | Year: 2012

Alpha-helical region substitution was applied to the SIAH1 and EL5 RING fingers. The Williams-Beuren syndrome transcription factor (WSTF) PHD_SIAH1 and WSTF PHD_EL5 RING fingers were created as the artificial ubiquitin-ligating enzyme (E3). These fingers possess E3 activities of mono-ubiquitination and poly-ubiquitination, respectively, with ubiquitin-conjugating enzyme (E2)-binding capabilities. Artificial E3s bind two zinc atoms and adopt a zinc-dependent ordered structure and ubiquitinate upon themselves without a substrate and a tag. Ubiquitination experiments using biotinylated ubiquitin showed that the WSTF PHD_EL5 RING finger is poly-ubiquitinated via residue Lys63 of ubiquitin. Substitution of alpha-helical region might be applicable to various RING fingers with mono-ubiquitination or poly-ubiquitination. © 2011 European Peptide Society and John Wiley & Sons, Ltd.

Yagami T.,Himeji Dokkyo University | Yamamoto Y.,Himeji Dokkyo University | Koma H.,Himeji Dokkyo University
Molecular Neurobiology | Year: 2014

Secretory phospholipase A2 (sPLA2s) are small secreted proteins (14-18 kDa) and require submillimolar levels of Ca 2+ for liberating arachidonic acid from cell membrane lipids. In addition to the enzymatic function, sPLA2 can exert various biological responses by binding to specific receptors. Physiologically, sPLA2s play important roles on the neurotransmission in the central nervous system and the neuritogenesis in the peripheral nervous system. Pathologically, sPLA2s are involved in the neurodegenerative diseases (e.g., Alzheimer's disease) and cerebrovascular diseases (e.g., stoke). The common pathology (e.g., neuronal apoptosis) of Alzheimer's disease and stroke coexists in the mixed dementia, suggesting common pathogenic mechanisms of the two neurological diseases. Among mammalian sPLA2s, sPLA 2-IB and sPLA2-IIA induce neuronal apoptosis in rat cortical neurons. The excess influx of calcium into neurons via l-type voltage-dependent Ca2+ channels mediates the two sPLA 2-induced apoptosis. The elevated concentration of intracellular calcium activates PKC, MAPK and cytosolic PLA2. Moreover, it is linked with the production of reactive oxygen species and apoptosis through activation of the superoxide producing enzyme NADPH oxidase. NADPH oxidase is involved in the neurotoxicity of amyloid β peptide, which impairs synaptic plasticity long before its deposition in the form of amyloid plaques of Alzheimer's disease. In turn, reactive oxygen species from NADPH oxidase can stimulate ERK1/2 phosphorylation and activation of cPLA2 and result in a release of arachidonic acid. sPLA2 is up-regulated in both Alzheimer's disease and cerebrovascular disease, suggesting the involvement of sPLA2 in the common pathogenic mechanisms of the two diseases. Thus, our review presents evidences for pathophysiological roles of sPLA2 in the central nervous system and neurological diseases. © 2013 Springer Science+Business Media.

Yoshii N.,Himeji Dokkyo University | Okamura E.,Himeji Dokkyo University
Journal of Physical Chemistry B | Year: 2011

The kinetics of membrane binding and dissociation of fluorinated bisphenol A (FBPA, (CF3)2C(C6H4OH) 2) is quantified by 1D 19F NMR spectra in situ. Although the bound and free components are in fast exchange, the rate constants and bound fraction is nonetheless determined from an analysis of the spectra. The analysis relies on the expression of 1D NMR signal intensity by a set of Bloch equations with exchange terms. The time span of the binding and dissociation of hydrophobic FBPA to large unilamellar vesicles of egg phosphatidylcholine (EPC) is 10-3 to 10-2 s. The rates of FBPA binding and dissociation are kept constant per EPC molecule even at different concentrations of the vesicle. The free energy of FBPA transfer is -20 ± 2 kJ/mol at 303 K. The process is entropy-driven. The efficiency of FBPA transfer is enhanced by a factor of 7 × 104, as compared with the hydrophilic 5-fluorouracil. © 2011 American Chemical Society.

Miyamoto K.,Himeji Dokkyo University
Scientific Reports | Year: 2014

The artificial WSTF PHD-EL5 RING finger was designed via ''α-helical region substitution'', and its structural model for the attachment of activated ubiquitin has been demonstrated. Chemical modifications of Cys residues, the circular dichroism spectra, and substrate-independent ubiquitination assays illustrated that theWSTFPHD-EL5 RING finger has E3 activity, and it is ubiquitinated via Lys14. Homology modeling calculations revealed that the WSTF PHD-EL5 RING finger possesses a classical RING fold for specific E2- E3 binding. The docking poses of the WSTF PHD-EL5 RING finger with the UbcH5b-ubiquitin conjugate provided insight into its functional E2 interaction and development of ubiquitination at the atomic level. The structural model of the artificial WSTF PHD-EL5 RING finger proposed by the present work is useful and may help to extend the strategy of a-helical region substitution.

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