Tondabayashi, Japan

Osaka Ohtani University

www.osaka-ohtani.ac.jp
Tondabayashi, Japan

Osaka Ohtani University is a private university in Tondabayashi, Osaka, Japan. The school was established in 1966 as a junior women's college. In 2006 it became coeducational, adopting the present name. Wikipedia.

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Replication-incompetent adenovirus (Ad) vectors have gained attention as gene delivery vehicles. Theoretically, no Ad genes should be expressed following transduction; however, Ad genes are expressed from the vector genome, leading to induction of cellular immunity against Ad proteins and Ad protein-induced toxicity. To suppress the leaky expression of Ad genes, a microRNA (miRNA) -regulated gene expression system was utilized. We developed novel Ad vectors by incorporating targeted sequences of miR-122a or miR-142-3p, which exhibit liver- or spleen-specific expression, respectively, in the 3′-untranslated region (UTR) of the E2A, E4, or pIX genes. These Ad vectors easily grew to high titers comparable to those of a conventional Ad vector in conventional human embryonic kidney 293 cells. The leaky expression of these Ad genes in mouse organs was significantly suppressed by 2- to 100-fold in an miRNA-dependent manner, compared with a conventional Ad vector, by the insertion of the miRNA-targeted sequences. Notably, the Ad vector carrying the miR-122a-targeted sequences into the 3′-UTR of the E4 gene (Ad-E4-122aT) expressed 1.5- to 34-fold higher and longer-term transgene expression and more than 20-fold lower levels of all the Ad early and late genes examined in the liver compared with a conventional Ad vector. miR-122a-mediated suppression of E4 gene expression in the liver significantly reduced the hepatotoxicity that an Ad vector causes via both adaptive and non-adaptive immune responses. Ad-E4-122aT would be a promising framework for efficient gene delivery due to its ability to mediate higher and longer-term transgene expression and lower hepatotoxicity than a conventional Ad vector. © 2015 The Pharmaceutical Society of Japan.


Tanaka K.,Osaka Ohtani University | Koyama Y.,Osaka Ohtani University
Journal of Neuroscience Research | Year: 2011

Some of the aquaporins (AQPs), a family of water channel proteins, are expressed in astrocytes. The expression of astrocytic AQPs is altered after brain insults, such as ischemia and head trauma. However, little is known about the regulation of AQP expressions. Endothelins (ETs), which are vasoconstrictor peptides, regulate several pathophysiological responses of astrocytes. In this study, the effects of ETs on AQP expressions and plasma membrane water permeability were examined in cultured rat astrocytes. Determination of AQP mRNA copy numbers revealed that AQP1 and AQP4 were expressed prominently in cultured astrocytes. ET-1 (100 nM) and Ala1,3,11,15-ET-1 (an ETB receptor agonist, 50 nM) decreased the AQP4 and AQP9 mRNA levels in cultured astrocytes, but the AQP1, -3, -5, and -8 mRNA levels remained unchanged. BQ788, an ETB receptor antagonist, reduced the effects of ET-1 on astrocytic AQP mRNAs, whereas FR139317, an ETA antagonist, had no effect. Immunoblot analyses revealed that treatment with ET-1 decreased the protein contents of AQP4 and AQP9 in both total cell lysates and plasma membrane fractions of cultured astrocytes. ET-1 and Ala1,3,11,15-ET-1 decreased hypoosmolarity-induced water influxes into cultured astrocytes. In the presence of 30 μM Hg2+, which inhibits water movement through AQP1 and AQP9, the hypoosmolarity-induced water influxes were reduced. Phloretin, an inhibitor of AQP9, did not greatly affect the water influxes. The ET-induced decreases in water influxes were obtained in the presence of Hg2+ and phloretin. These results suggest that ET is a factor that regulates AQP expressions and water permeability in astrocytes. © 2010 Wiley-Liss, Inc.


Koyama Y.,Osaka Ohtani University | Tanaka K.,Osaka Ohtani University
Neuroscience Letters | Year: 2010

Aquaporins (AQPs) comprise a family of water channel proteins, some of which are expressed in brain. Expressions of brain AQPs are altered after brain insults, such as ischemia and head trauma. However, little is known about the regulation of brain AQP expression. Endothelins (ETs), vasoconstrictor peptides, regulate several pathophysiolgical responses of damaged nerve tissues via ETB receptors. To show possible roles of ETB receptors in the regulation of brain AQP expression, the effects of intracerebroventricular administration of an ETB agonist were examined in rat brain. In the cerebrum, the copy numbers of AQP4 mRNAs were highest among AQP1, 3, 4, 5 and 9. Continuous administration of 500 pmol/day Ala1,3,11,15-ET-1, an ETB selective agonist, into rat brain for 7 days decreased the level of AQP4 mRNA in the cerebrum, but had no effect on AQP1, 3, 5 and 9 mRNA levels. The level of AQP4 protein in the cerebrum decreased by the administration of Ala1,3,11,15-ET-1. Immunohistochemical observations of Ala1,3,11,15-ET-1-infused rats showed that GFAP-positive astrocytes, but not neurons, activated microglia or brain capillary endothelial cells, had immunoreactivity for AQP4. These findings indicate that activation of brain ETB receptors causes a decrease in AQP4 expression, suggesting that ET down-regulates brain AQP4 via ETB receptors. © 2009 Elsevier Ireland Ltd. All rights reserved.


Koyama Y.,Osaka Ohtani University
Frontiers in Cellular Neuroscience | Year: 2015

Astrocytes play an essential role in supporting brain functions in physiological and pathological states. Modulation of their pathophysiological responses have beneficial actions on nerve tissue injured by brain insults and neurodegenerative diseases, therefore astrocytes are recognized as promising targets for neuroprotective drugs. Recent investigations have identified several astrocytic mechanisms for modulating synaptic transmission and neural plasticity. These include altered expression of transporters for neurotransmitters, release of gliotransmitters and neurotrophic factors, and intercellular communication through gap junctions. Investigation of patients with mental disorders shows morphological and functional alterations in astrocytes. According to these observations, manipulation of astrocytic function by gene mutation and pharmacological tools reproduce mental disorder-like behavior in experimental animals. Some drugs clinically used for mental disorders affect astrocyte function. As experimental evidence shows their role in the pathogenesis of mental disorders, astrocytes have gained much attention as drug targets for mental disorders. In this paper, I review functional alterations of astrocytes in several mental disorders including schizophrenia, mood disorder, drug dependence, and neurodevelopmental disorders. The pharmacological significance of astrocytes in mental disorders is also discussed. ©2015 Koyama.


Koyama Y.,Osaka Ohtani University | Michinaga S.,Osaka Ohtani University
Journal of Pharmacological Sciences | Year: 2012

The receptors for endothelins (ETs) are classified into the ETA and ETB types. ETB receptors are highly expressed in astrocytes, but pharmacological usages of this receptor are not clarified. In this article, recent studies on the pathophysiological roles of astrocytic ETB receptors in the brain are reviewed. The administration of ETB agonists and antagonists in nerve injury models showed that several astrocytic functions are regulated by ETB receptors. The activation of ETB receptors causes morphological alterations and proliferation of cultured astrocytes. Astrocytes produce various bio-active substances that can affect damage to nerve tissues. ETs stimulate the production of neurotrophic factors by astrocytes. This action improves impaired brain functions. On the other hand, the production of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF), which induce brain edema, also are stimulated by ETs. These findings indicate that astrocytic functions are effectively regulated by modulations of ETB receptors. In brain insults and neurodegenerative diseases, these functions of astrocytes affect the protection and repair of damaged nerve tissues. Thus, astrocytic ETB receptors could be a target for novel types of neuroprotective drugs. © The Japanese Pharmacological Society.


Expressions of vascular endothelial growth factor (VEGF) receptors in astrocytes are increased in damaged brains. To clarify the regulatory mechanisms of VEGF receptors, the effects of endothelin-1 (ET-1) were examined in rat cultured astrocytes. Expressions of VEGF-R1 and -R2 receptor mRNA were at similar levels, whereas the mRNA expressions of VEGF-R3 and Tie-2, a receptor for angiopoietins, were lower. Placenta growth factor, a selective agonist of the VEGF-R1 receptor, induced phosphorylation of focal adhesion kinase (FAK) and extracellular signal regulated kinase 1/2 (ERK1/2). Phosphorylations of FAK and ERK 1/2 were also stimulated by VEGF-E, a selective VEGF-R2 agonist. Increased phosphorylations of FAK and ERK1/2 by VEGF165 were reduced by selective antagonists for VEGF-R1 and -R2. Treatment with ET-1 increased VEGF-R1 mRNA and protein levels. The effects of ET-1 on VEGF-R1 mRNA were mimicked by Ala(1,3,11,15) -ET-1, a selective agonist for ETB receptors, and inhibited by BQ788, an ETB antagonist. ET-1 did not affect the mRNA levels of VEGF-R2, -R3, and Tie-2. Pre-treatment with ET-1 potentiated the effects of placenta growth factor on phosphorylations of FAK and ERK1/2. These findings suggest that ET-1 induces up-regulation of VEGF-R1 receptors in astrocytes, and potentiates VEGF signals in damaged nerve tissues. To clarify the regulatory mechanisms of vascular endothelial growth factor (VEGF) receptors, the effects of endothelin-1 (ET-1) were examined in rat cultured astrocytes. Effects of selective VEGF-R1 and R2 agonist showed that these receptors were linked to focal adhesion kinase (FAK) and extracellular signal regulated kinase 1/2 (ERK1/2). Treatment with ET-1 increased expression of VEGF-R1, which was mediated by ETB receptors. Pre-treatment with ET-1 potentiated the VEGF-R1-mediated activations of FAK and ERK1/2. These findings suggest that ET-1 induces up-regulation of VEGF-R1 receptors in astrocytes. © 2014 International Society for Neurochemistry.


Yasuda M.,Osaka Ohtani University
Rorschachiana | Year: 2015

Eye movements during the Rorschach Inkblot Method (RIM) were monitored to investigate the existence of location recognition failures that were accompanied by clients' explanations in the inquiry phase. We hypothesized that perceived locations may have differed from actual explained locations if fixations did not occur -and visual attention was diverted to other locations -just before the response in the free association phase. The eye movement data of 29 participants under a Rorschach administration were collected, and 688 responses were obtained. Of these, 195 responses that involved perception of small, specific locations were used to investigate the association between pre-response eye movements and queried locations. Six responses of three participants showed fixations within 3 s before the time of response at locations different from the locations provided in the explanation. Responses made to similar but different locations were indicative of potential failures of location recognition. © 2015 Hogrefe Publishing.


Katsuki H.,Kumamoto University | Michinaga S.,Osaka Ohtani University
Vitamins and Hormones | Year: 2012

Non-ergot-type dopamine receptor agonists such as ropinirole are used for treatment of Parkinson disease, but they frequently produce adverse actions characterized by sleepiness and sleep attacks. Because these symptoms are similar to those observed in patients with narcolepsy, a sleep disorder caused by degeneration of hypothalamic orexin neurons, involvement of orexinergic system in the adverse drug actions is suspected. We found that ropinirole and other non-ergot dopamine D 2 receptor agonists cause selective loss of orexin-immunoreactive neurons in organotypic slice culture of rat hypothalamus. The mechanism of this action is considered to involve D 2 receptor-mediated presynaptic suppression of glutamatergic excitatory inputs to orexin neurons because continuous silencing of excitatory activity of orexin neurons can deplete orexin from cell bodies. In addition, Parkinson disease itself may accompany loss of orexin neurons. Disturbance of orexinergic system may play an important role in sleep/arousal dysfunctions under these and other clinical conditions. © 2012 Elsevier Inc..


Koyama Y.,Osaka Ohtani University
Neurochemistry International | Year: 2014

Phenotypic conversion of astrocytes from resting to reactive (i.e., astrocytic activation) occurs in numerous brain disorders. Astrocytic activation in severely damaged brain regions often leads to glial scar formation. Because astrocytic activation and glial scar largely affect the vulnerability and tissue repair of damaged brain, numerous studies have been made to clarify mechanisms regulating the astrocytic phenotype. The phenotypic conversion is accompanied by the increased expression of intermediate filament proteins and the induction of hypertrophy in reactive astrocytes. Severe brain damage results in proliferation and migration of reactive astrocytes, which lead to glial scar formations at the injured areas. Gliogenesis from neural progenitors in the adult brain is also involved in astrocytic activation and glial scar formation. Recent studies have shown that increased expression of connexin 43, aquaporin 4, matrix metalloproteinase 9, and integrins alter the function of astrocytes. The transcription factors: STAT3, OLIG2, SMAD, NF-κB, and Sp1 have been suggested to play regulatory roles in astrocytic activation and glial scar formation. In this review, I discuss the roles of these key molecules regulating the pathophysiological functions of reactive astrocytes. © 2014 Elsevier Ltd. All rights reserved.


Heat transfer of magnetothermal convection with the presence or absence of the magnetic force acting on the susceptibility gradient (fsc ) was examined by three-dimensional numerical computations. Thermal convection of water enclosed in a shallow cylindrical vessel (diameter over vessel height = 6.0) with the Rayleigh-Benard model was adopted as the model, under the conditions of Prandtl number 6.0 and Ra number 7000, respectively. The momentum equations of convection were nondimensionalized, which involved the term of fsc and the term of magnetic force acting on the magnetic field gradient (fb ). All the computations resulted in axisymmetric steady rolls. The values of the averaged Nu, the averaged velocity components U, V, and W, and the isothermal distributions and flow patterns were almost completely the same, regardless of the presence or absence of the term of fsc .Asa result, we found that the effect of fsc was extremely small, although much previous research emphasized the effect with paramagnetic solutions under an unsteady state. The magnitude of fsc depends not only on magnetic conditions (magnitudes of magnetic susceptibility and magnetic flux density), but also on the thermal properties of the solution (thermal conductivity, thermal diffusivity, and viscosity). Therefore the effect of fb becomes dominant on the magnetothermal convection. Active control over the density gradient with temperature will be required to advance heat transfer with the effect of fsc. © 2016 Syou Maki. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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