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Search Results: 1 - 10 of 3996 matches for " Toshiharu Suzuki "
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A Role of Chaotic Phenomenon and the Central Place System in a Firm’s Location Selections  [PDF]
Toshiharu Ishikawa
Theoretical Economics Letters (TEL) , 2012, DOI: 10.4236/tel.2012.21019
Abstract: When a manufacturing firm has a plan to build a factory, the determination of the factory’s location site is one of the most important elements in the plan. Since the manufacturer does not have enough information of economic conditions of all potential location sites, the manufacturer cannot determine immediately its location site. A series of steps are taken to determine the location place. The firm makes range of searching area small step by step toward the site deter-mination; 1) Determination of a prospective region in a large space, 2) Selection of a potential area in that region, 3) Choice of an urban district in that area, 4) Decision of a site in the district. This paper proposes that chaotic phenome-non, which is appeared in the calculation processes to specify the optimal location site, may be used to identify a pro-spective region. And then, it is shown in the paper that the central place systems laid in the region play a role in the se-lection of a potential area for the factory location. This paper elucidates how a firm searches step by step an appropriate factory’s location within a large geographical area.
Suppression of Alzheimer’s Disease-Related Phenotypes by Geranylgeranylacetone in Mice
Tatsuya Hoshino, Koichiro Suzuki, Takahide Matsushima, Naoki Yamakawa, Toshiharu Suzuki, Tohru Mizushima
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076306
Abstract: Amyloid-β peptide (Aβ) plays an important role in the pathogenesis of Alzheimer’s disease (AD). Aβ is generated by the secretase-mediated proteolysis of β-amyloid precursor protein (APP), and cleared by enzyme-mediated degradation and phagocytosis. Transforming growth factor (TGF)-β1 stimulates this phagocytosis. We recently reported that the APP23 mouse model for AD showed fewer AD-related phenotypes when these animals were crossed with transgenic mice expressing heat shock protein (HSP) 70. We here examined the effect of geranylgeranylacetone, an inducer of HSP70 expression, on the AD-related phenotypes. Repeated oral administration of geranylgeranylacetone to APP23 mice for 9 months not only improved cognitive function but also decreased levels of Aβ, Aβ plaque deposition and synaptic loss. The treatment also up-regulated the expression of an Aβ-degrading enzyme and TGF-β1 but did not affect the maturation of APP and secretase activities. These outcomes were similar to those observed in APP23 mice genetically modified to overexpress HSP70. Although the repeated oral administration of geranylgeranylacetone did not increase the level of HSP70 in the brain, a single oral administration of geranylgeranylacetone significantly increased the level of HSP70 when Aβ was concomitantly injected directly into the hippocampus. Since geranylgeranylacetone has already been approved for use as an anti-ulcer drug and its safety in humans has been confirmed, we propose that this drug be considered as a candidate drug for the prevention of AD.
Diagnosis and Treatment of Attention-Deficit Hyperactivity Disorder in Patients with Chronic Pain  [PDF]
Satoshi Kasahara, Yumiko Okamura, Ko Matsudaira, Hiroyuki Oka, Yoshie Suzuki, Yasuko Murakami, Toshiharu Tazawa, Hayato Shimazaki, Shin-ichi Niwa, Yoshitsugu Yamada
Open Journal of Psychiatry (OJPsych) , 2017, DOI: 10.4236/ojpsych.2017.74023
Abstract: Aims: To investigate rates of attention-deficit hyperactivity disorder (ADHD) in patients with chronic pain attending a pain clinic, the effects of a screening measure for ADHD in patients with chronic pain, and the effects of ADHD drugs on both pain and ADHD symptoms. Methods: We retrospectively surveyed 110 patients with chronic pain visiting the Anesthesiology and Pain Relief Center at the University of Tokyo in Japan, who had also consulted a psychiatrist, between April 2012 and July 2015. Results: Of the total of 110 patients with chronic pain, 35 (31.8%) were also diagnosed with ADHD, and the average Wender Utah Rating Scale (WURS) score among the ADHD patients was 39.0 ± 22.1 (n = 25). Only 36.0% of these patients exceeded the cutoff value, suggesting that 64.0% of the patients with ADHD were not identified by screening with the WURS. Twenty-six patients initiated treatment with ADHD medication, with dosage adjustment completed in 21. Of these 21 patients 20 (95.0%) had improved ADHD symptoms. Improved pain symptoms were observed in 14 patients (66.6%), with a reduction in the pain numerical rating scale of 64.7% ± 30.1%. Conclusions: This is the first study investigating the comorbidity of ADHD and chronic pain at pain clinics showing a high level of comorbidity and amelioration of pain and ADHD symptoms with treatment. Careful interpretation is required when the WURS is used to screen patients with chronic pain.
Fixed Point Theorem and Fractional Differential Equations with Multiple Delays Related with Chaos Neuron Models  [PDF]
Toshiharu Kawasaki, Masashi Toyoda
Applied Mathematics (AM) , 2015, DOI: 10.4236/am.2015.613192
Abstract: In this paper, we show a fixed point theorem which deduces to both of Lou’s fixed point theorem and de Pascale and de Pascale’s fixed point theorem. Moreover, our result can be applied to show the existence and uniqueness of solutions for fractional differential equations with multiple delays. Using the theorem, we discuss the fractional chaos neuron model.
Association between Proximity to a Health Center and Early Childhood Mortality in Madagascar
Saori Kashima, Etsuji Suzuki, Toshiharu Okayasu, Razafimahatratra Jean Louis, Akira Eboshida, S. V. Subramanian
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0038370
Abstract: Objective To evaluate the association between proximity to a health center and early childhood mortality in Madagascar, and to assess the influence of household wealth, maternal educational attainment, and maternal health on the effects of distance. Methods From birth records of subjects in the Demographic and Health Survey, we identified 12565 singleton births from January 2004 to August 2009. After excluding 220 births that lacked global positioning system information for exposure assessment, odds ratios (ORs) and their 95% confidence intervals (CIs) for neonatal mortality and infant mortality were estimated using multilevel logistic regression models, with 12345 subjects (level 1), nested within 584 village locations (level 2), and in turn nested within 22 regions (level 3). We additionally stratified the subjects by the birth order. We estimated predicted probabilities of each outcome by a three-level model including cross-level interactions between proximity to a health center and household wealth, maternal educational attainment, and maternal anemia. Results Compared with those who lived >1.5–3.0 km from a health center, the risks for neonatal mortality and infant mortality tended to increase among those who lived further than 5.0 km from a health center; the adjusted ORs for neonatal mortality and infant mortality for those who lived >5.0–10.0 km away from a health center were 1.36 (95% CI: 0.92–2.01) and 1.42 (95% CI: 1.06–1.90), respectively. The positive associations were more pronounced among the second or later child. The distance effects were not modified by household wealth status, maternal educational attainment, or maternal health status. Conclusions Our study suggests that distance from a health center is a risk factor for early childhood mortality (primarily, infant mortality) in Madagascar by using a large-scale nationally representative dataset. The accessibility to health care in remote areas would be a key factor to achieve better infant health.
Constitutive Cleavage of the Single-Pass Transmembrane Protein Alcadeinα Prevents Aberrant Peripheral Retention of Kinesin-1
Chiaki Maruta, Yuhki Saito, Saori Hata, Naoya Gotoh, Toshiharu Suzuki, Tohru Yamamoto
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043058
Abstract: Various membrane proteins are shed by proteinases, constitutively and/or when stimulated by external signals. While the physiological significance of external signal-induced cleavages has been intensely investigated, relatively little is known about the function of constitutive cleavages. Alcadeinα (Alcα; also called Calsyntenin-1) is an evolutionarily conserved type I single-pass transmembrane protein that binds to kinesin-1 light chain (KLC) to activate kinesin-1's transport of Alcα-containing vesicles. We found that Alcα was constitutively and efficiently cleaved to liberate its ectodomain into the extracellular space, and that full-length Alcα protein was rarely detected on the cell surface. The secretion efficiency of the ectodomain was unaltered by a mutation that both abolished Alcα's KLC-binding activity and attenuated its peripheral transport, suggesting that Alcα's cleavage occurred, at least partly, en route to the cell surface. We further demonstrated that uncleavable mutant Alcα proteins readily accumulated on the cell surface and induced aberrant peripheral recruitment of KLC1 and kinesin heavy chain. Our observations suggest that Alcα is efficiently processed in part to minimize the inappropriate peripheral retention of kinesin-1. This role might exemplify the functional relevance of the constitutive cleavage of single-pass transmembrane proteins.
Mechanism of Intramembrane Cleavage of Alcadeins by γ-Secretase
Yi Piao, Ayano Kimura, Satomi Urano, Yuhki Saito, Hidenori Taru, Tohru Yamamoto, Saori Hata, Toshiharu Suzuki
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0062431
Abstract: Background Alcadein proteins (Alcs; Alcα, Alcβand Alcγ) are predominantly expressed in neurons, as is Alzheimer's β-amyloid (Aβ) precursor protein (APP). Both Alcs and APP are cleaved by primary α- or β-secretase to generate membrane-associated C-terminal fragments (CTFs). Alc CTFs are further cleaved by γ-secretase to secrete p3-Alc peptide along with the release of intracellular domain fragment (Alc ICD) from the membrane. In the case of APP, APP CTFβ is initially cleaved at the ε-site to release the intracellular domain fragment (AICD) and consequently the γ-site is determined, by which Aβ generates. The initial ε-site is thought to define the final γ-site position, which determines whether Aβ40/43 or Aβ42 is generated. However, initial intracellular ε-cleavage sites of Alc CTF to generate Alc ICD and the molecular mechanism that final γ-site position is determined remains unclear in Alcs. Methodology Using HEK293 cells expressing Alcs plus presenilin 1 (PS1, a catalytic unit of γ-secretase) and the membrane fractions of these cells, the generation of p3-Alc possessing C-terminal γ-cleavage site and Alc ICD possessing N-terminal ε-cleavage site were analysed with MALDI-TOF/MS. We determined the initial ε-site position of all Alcα, Alcβ and Alcγ, and analyzed the relationship between the initially determined ε-site position and the final γ-cleavage position. Conclusions The initial ε-site position does not always determine the final γ-cleavage position in Alcs, which differed from APP. No additional γ-cleavage sites are generated from artificial/non-physiological positions of ε-cleavage for Alcs, while the artificial ε-cleavage positions can influence in selection of physiological γ-site positions. Because alteration of γ-secretase activity is thought to be a pathogenesis of sporadic Alzheimer's disease, Alcs are useful and sensitive substrate to detect the altered cleavage of substrates by γ-secretase, which may be induced by malfunction of γ-secretase itself or changes of membrane environment for enzymatic reaction.
Effects of Heparin and Enoxaparin on APP Processing and Aβ Production in Primary Cortical Neurons from Tg2576 Mice
Hao Cui, Amos C. Hung, David W. Klaver, Toshiharu Suzuki, Craig Freeman, Christian Narkowicz, Glenn A. Jacobson, David H. Small
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023007
Abstract: Background Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice. Methodology/Principal Findings We examined whether heparin and enoxaparin influence APP processing and inhibit Aβ production in primary cortical cell cultures. Heparin and enoxaparin were incubated with primary cortical cells derived from Tg2576 mice, and the level of APP and proteolytic products of APP (sAPPα, C99, C83 and Aβ) was measured by western blotting. Treatment of the cells with heparin or enoxaparin had no significant effect on the level of total APP. However, both GAGs decreased the level of C99 and C83, and inhibited sAPPα and Aβ secretion. Heparin also decreased the level of β-secretase (BACE1) and α-secretase (ADAM10). In contrast, heparin had no effect on the level of ADAM17. Conclusions/Significance The data indicate that heparin and enoxaparin decrease APP processing via both α- and β-secretase pathways. The possibility that GAGs may be beneficial for the treatment of AD needs further study.
Intracellular Trafficking of the Amyloid β-Protein Precursor (APP) Regulated by Novel Function of X11-Like
Yuhki Saito, Mayu Akiyama, Yoichi Araki, Akio Sumioka, Maki Shiono, Hidenori Taru, Tadashi Nakaya, Tohru Yamamoto, Toshiharu Suzuki
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0022108
Abstract: Background Amyloid β (Aβ), a causative peptide of Alzheimer's disease, is generated by intracellular metabolism of amyloid β-protein precursor (APP). In general, mature APP (mAPP, N- and O-glycosylated form) is subject to successive cleavages by α- or β-, and γ-secretases in the late protein secretory pathway and/or at plasma membrane, while immature APP (imAPP, N-glycosylated form) locates in the early secretory pathway such as endoplasmic reticulum or cis-Golgi, in which imAPP is not subject to metabolic cleavages. X11-like (X11L) is a neural adaptor protein composed of a phosphotyrosine-binding (PTB) and two C-terminal PDZ domains. X11L suppresses amyloidogenic cleavage of mAPP by direct binding of X11L through its PTB domain, thereby generation of Aβ lowers. X11L expresses another function in the regulation of intracellular APP trafficking. Methodology In order to analyze novel function of X11L in intracellular trafficking of APP, we performed a functional dissection of X11L. Using cells expressing various domain-deleted X11L mutants, intracellular APP trafficking was examined along with analysis of APP metabolism including maturation (O-glycosylation), processing and localization of APP. Conclusions X11L accumulates imAPP into the early secretory pathway by mediation of its C-terminal PDZ domains, without being bound to imAPP directly. With this novel function, X11L suppresses overall APP metabolism and results in further suppression of Aβ generation. Interestingly some of the accumulated imAPP in the early secretory pathway are likely to appear on plasma membrane by unidentified mechanism. Trafficking of imAPP to plasma membrane is observed in other X11 family proteins, X11 and X11L2, but not in other APP-binding partners such as FE65 and JIP1. It is herein clear that respective functional domains of X11L regulate APP metabolism at multiple steps in intracellular protein secretory pathways.
Therapeutic Strategies for SLE Involving Cytokines: Mechanism-Oriented Therapies Especially IFN- Targeting Gene Therapy
Toshiharu Hayashi
Journal of Biomedicine and Biotechnology , 2010, DOI: 10.1155/2010/461641
Abstract: Systemic lupus erythematosus (SLE: lupus) is a chronic complicated autoimmune disease and pathogenesis is still unclear. However, key cytokines have been recognized. Interferon (IFN)- and also IFN/ are of particular importance. Depending on the concept that lupus is a helper T(Th)1 disease and that dendritic cells (DCs) determine the direction of lupus, balance shift of Th1/Th2 and immunogenic/tolerogenic DCs is reviewed for therapy. (IFN)-- and IFN-/-targeted (gene) therapies are introduced. These consist of Th1/Th2 balance shift and elimination of IFN- and IFN--related cytokines such as (interleukin)IL-12 and IL-18. Other approaches include suppression of immunocompetent cells, normalization of abnormal T-cell function, costimulation blockade, B lymphocyte stimulator (Blys) blockade, and suppression of nephritic kidney inflammation. Moreover, balance shift of IFN-/ and tumor necrosis factor (TNF)- together with regulatory T(Treg) cells are briefely introduced. Clinical application will be discussed.
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