Ishikawa-Sasaki K.,Aichi University |
Sasaki J.,Aichi University |
Taniguchi K.,Aichi University
Journal of Virology | Year: 2014
Phosphatidylinositol 4-kinase IIIβ (PI4KB) is a host factor required for the replication of certain picornavirus genomes. We previously showed that nonstructural proteins 2B, 2BC, 2C, 3A, and 3AB of Aichi virus (AiV), a picornavirus, interact with the Golgi protein, acyl-coenzyme A binding domain containing 3 (ACBD3), which interacts with PI4KB. These five viral proteins, ACBD3, PI4KB, and the PI4KB product phosphatidylinositol 4-phosphate (PI4P) colocalize to the AiV RNA replication sites (J. Sasaki et al., EMBO J. 31:754-766, 2012). We here examined the roles of these viral and cellular molecules in the formation of AiV replication complexes. Immunofluorescence microscopy revealed that treatment of AiV polyprotein-expressing cells with a small interfering RNA targeting ACBD3 abolished colocalization of the viral 2B, 2C, and 3A proteins with PI4KB. A PI4KB-specific inhibitor also prevented their colocalization. Virus RNA replication increased the level of cellular PI4P without affecting that of PI4KB, and individual expression of 2B, 2BC, 2C, 3A, or 3AB stimulated PI4P generation. These results suggest that the viral protein/ACBD3/PI4KB complex plays an important role in forming the functional replication complex by enhancing PI4P synthesis. Of the viral proteins, 3A and 3AB were shown to stimulate the in vitro kinase activity of PI4KB through forming a 3A or 3AB/ACBD3/PI4KB complex, whereas the ACBD3-mediated PI4KB activation by 2B and 2C remains to be demonstrated. Copyright. © 2014, American Society for Microbiology.
Sasaki J.,Aichi University |
Ishikawa K.,Aichi University |
Arita M.,Japan National Institute of Infectious Diseases |
Taniguchi K.,Aichi University
EMBO Journal | Year: 2012
Phosphatidylinositol 4-kinase IIIÎ 2 (PI4KB) is a host factor required for genome RNA replication of enteroviruses, small non-enveloped viruses belonging to the family Picornaviridae. Here, we demonstrated that PI4KB is also essential for genome replication of another picornavirus, Aichi virus (AiV), but is recruited to the genome replication sites by a different strategy from that utilized by enteroviruses. AiV non-structural proteins, 2B, 2BC, 2C, 3A, and 3AB, interacted with a Golgi protein, acyl-coenzyme A binding domain containing 3 (ACBD3). Furthermore, we identified previously unknown interaction between ACBD3 and PI4KB, which provides a novel manner of Golgi recruitment of PI4KB. Knockdown of ACBD3 or PI4KB suppressed AiV RNA replication. The viral proteins, ACBD3, PI4KB, and phophatidylinositol-4-phosphate (PI4P) localized to the viral RNA replication sites. AiV replication and recruitment of PI4KB to the RNA replication sites were not affected by brefeldin A, in contrast to those in enterovirus infection. These results indicate that a viral protein/ACBD3/PI4KB complex is formed to synthesize PI4P at the AiV RNA replication sites and plays an essential role in viral RNA replication. © 2012 European Molecular Biology Organization | All Rights Reserved.
Hirota T.,Vanderbilt University |
Kishi T.,Aichi University
Journal of Clinical Psychiatry | Year: 2013
Objective: Although antipsychotics have been used empirically to prevent the development of postoperative delirium, there has been no confirming evidence to support their use. Thus, we conducted a systematic review and a meta-analysis to elucidate their efficacy and tolerability in surgical patients. Data Sources: MEDLINE, EMBASE, the Cochrane Library databases, CINAHL, and PsycINFO were searched up to February 2013 without language restrictions, using the following keywords: (antipsychotics OR [nonproprietary name of each antipsychotic medication, separated by OR]) AND delirium AND (randomized OR random OR randomly). Study Selection: Randomized controlled trials comparing prophylactic use of antipsychotics with placebo in surgical patients were included. Data Extraction: Two authors extracted and scrutinized the data. The risk ratio (RR), 95% confidence interval (CI), number needed to treat (NNT), and standardized mean difference were used. Results: Six studies (3 haloperidol, 1 olanzapine, and 2 risperidone) including 1,689 surgical patients were identified. The results showed significant efficacy in reducing the occurrence of delirium (RR = 0.50, 95% CI = 0.34 to 0.73, P = .0003; NNT = 7, P = .001, 6 studies). Sensitivity analysis showed that second-generation antipsychotics were superior to placebo (RR = 0.36, P < .00001; NNT = 4, P < .00001), whereas haloperidol failed to show superiority to placebo. There were no statistically significant differences between groups in severity of delirium, discontinuation rate, or rates of several adverse events. Conclusions: Our results suggest that secondgeneration antipsychotics are more beneficial than placebo for preventing the incidence of delirium.Among patients who do develop delirium, the severity of delirium is not reduced in those who received prophylactic antipsychotics. © Copyright 2013 Physicians Postgraduate Press, Inc.
Hirota T.,Vanderbilt University |
Kishi T.,Aichi University
Schizophrenia Research | Year: 2013
Objective: Adenosine has been reported to interact with dopamine and glutamate of which are currently central pathophysiology of schizophrenia. Further, there have been emerging reports that patients with bipolar disorder (BD) have pathophysiological changes of the purinergic system. Thus, we performed a systematic review and meta-analysis of adenosine modulators in these disorders. Method: We searched PubMed, EMBASE, the Cochrane Library databases, CINAHL, and PsycINFO up to April 25, 2013. Randomized controlled trials comparing adenosine modulator adjuvant therapy with placebo in patients with schizophrenia and BD were included. Primary outcome measures were Positive and Negative Syndrome Scale (PANSS) and Young Mania Rating Scales (YMRS). The risk ratio, 95% confidence interval, and standardized mean differences (SMD) were used. Results: Nine studies, including six studies in schizophrenia (total n. = 457) and three studies in BD (total n. = 289) were included. Overall, adenosine modulators were superior to placebo in PANSS total scores (SMD. = -. 1.07, p. = 0.01) and positive and general but not negative symptom subscale scores in schizophrenia. Individually, allopurinol failed to show its superiority to placebo in all primary outcome measures in schizophrenia. In BD, data from pooled adenosine modulators indicated significant reduction of YMRS scores in comparison to placebo (SMD. = -. 0.39, p. = 0.004). Conclusions: Our results suggest that adenosine modulator adjuvant therapy is more beneficial in overall psychopathology (especially positive symptoms) in schizophrenia and in treating mania episodes of BD in comparison to placebo. The limited sample size of available studies suggests that more research should be done to evaluate both efficacy and tolerability of these medications. © 2013 Elsevier B.V.
Miyoshi M.,Aichi University
Ocean Development and International Law | Year: 2012
China's recent claims to a large "U-shaped" area in the South China Sea, involving the disputed Spratly and Paracel Islands, has given rise to a number of serious criticisms not only from neighboring states, but also some states beyond the region. The claim also raises a number of theoretical questions, including whether historic title claims without hard evidence have validity under international law. This article explores this and other issues raised by China's U-shaped claim. © Taylor & Francis Group, LLC.
Higashiguchi T.,Aichi University
Nutrition | Year: 2013
Objective: " iEat®" (EN Otsuka Pharmaceutical Co. Ltd.; study diet), a food product that resembles an ordinary meal in appearance but is cooked to soften, was compared with foods provided to patients with impaired mastication (modified traditional diet) to investigate the influence of the appearance of foods on the consumption rate, dietary nutrition intake, and satisfaction level. Methods: After serving the study participants the modified traditional diet on days 1 and 2, the study diet on days 3, 4, and 5, and the modified traditional diet on days 6 and 7, the consumption rates were measured by weight difference. The amounts of dietary nutrition intake were calculated from the consumption rates. Satisfaction levels were evaluated by a questionnaire completed by the participants and their health care professionals after each meal. Results: No significant difference in consumption rates was observed between the study diet and the modified traditional diet. The amounts of dietary nutrition intake of energy and protein were significantly higher for the study diet than for the modified traditional diet. The study diet showed higher satisfaction levels in terms of " appearance" when evaluated by the participants, and " joy of eating" and " overall satisfaction level" when evaluated by the health care professionals. Conclusion: The study diet has potential to become a new dietary option for patients with impaired mastication. © 2013 Elsevier Inc.
Tsutsumi Y.,Aichi University
Japanese Journal of Clinical Oncology | Year: 2012
Objective: Apocrine carcinoma, a subtype of invasive ductal carcinoma of the breast, expresses androgen receptor (AR), but often lacks estrogen receptor (ER) and progesterone receptor (PgR). In the present study, the author immunohistochemically defined apocrine-type carcinoma as ER-/PgR-/AR+ invasive ductal carcinoma and analyzed the significance of apocrine-type carcinoma as triple-negative breast cancer. Methods: Four hundred and forty breast cancers from 429 cases were immunostained for estrogen receptor, progesterone receptor, androgen receptor, human epidermal growth factor receptor type 2 (HER2), p53, Ki-67 and epidermal growth factor receptor. The lesions included 58 in situ malignancies (including 13 apocrine-type lesions) and 325 invasive ductal carcinomas (including 44 apocrine type). Results: Of 91 estrogen receptor-negative invasive ductal carcinomas, 44 (48%) belonged to apocrine-type carcinoma, and overexpression of human epidermal growth factor receptor type 2 and p53 was observed in 23 (52%) and 33 (75%), respectively. Histologically, 22 (50%) were categorized as classical apocrine carcinoma. Among 281 non-apocrine invasive ductal carcinomas, 30 (11%) were quadruple-negative (ER-/PgR-/AR-/HER2-) and 17 (6%) were hormone receptor-negative and human epidermal growth factor receptor type 2-overexpressed. Invasive ductal carcinomas in the triple-negative breast cancer category (n = 51) were divided into triple-negative, androgen receptor-positive (apocrine, n = 21) and quadruple-negative (non-apocrine, n = 30). p53 overexpression was more often seen in the apocrine-type triple-negative breast cancer (18/21 = 86%) than in the non-apocrine type (14/30= 46%) (P< 0.05). Ki-67 labeling was significantly higher in the non-apocrine type (58%) than in the apocrine type (37%) (P< 0.01). Epidermal growth factor receptor is consistently expressed in triple-negative breast cancers (16/16= 100% in apocrine and 18/20= 90% in non-apocrine). Conclusions: Androgen receptor should be added to immunohistochemical panels, since apocrine-type invasive ductal carcinoma, resembling basal-like phenotypes, may show clinical behaviors different from the basal-like triple-negative breast cancer. © The Author 2012. Published by Oxford University Press. All rights reserved.
Uezumi A.,Health Science University |
Fukada S.-I.,Osaka University |
Yamamoto N.,Aichi University |
Takeda S.,National Institute of Neuroscience |
Tsuchida K.,Health Science University
Nature Cell Biology | Year: 2010
Ectopic fat deposition in skeletal muscle is closely associated with several disorders, however, the origin of these adipocytes is not clear, nor is the mechanism of their formation. Satellite cells function as adult muscle stem cells but are proposed to possess multipotency. Here, we prospectively identify PDGFRα+ mesenchymal progenitors as being distinct from satellite cells and located in the muscle interstitium. We show that, of the muscle-derived cell populations, only PDGFRα+ cells show efficient adipogenic differentiation both in vitro and in vivo. Reciprocal transplantations between regenerating and degenerating muscles, and co-culture experiments revealed that adipogenesis of PDGFRα+ cells is strongly inhibited by the presence of satellite cell-derived myofibres. These results suggest that PDGFRα+ mesenchymal progenitors are the major contributor to ectopic fat cell formation in skeletal muscle, and emphasize that interaction between muscle cells and PDGFRα+ mesenchymal progenitors, not the fate decision of satellitecells, has a considerable impact on muscle homeostasis. © 2010 Macmillan Publishers Limited. All rights reserved.
Kishi T.,Aichi University |
Iwata N.,Aichi University
Journal of Psychiatric Research | Year: 2013
Background: We examined whether N-methyl d-aspartate (NMDA) receptor antagonists as adjunctive therapy have therapeutic potential for schizophrenia treatment. Method: Systematic review of PubMed, Cochrane Library, PsycINFO and Google Scholar up until October 2012 and meta-analysis of randomized placebo-controlled trials were performed. Risk ratio (RR), 95% confidence intervals (CI), numbers-needed-to-harm (NNH), and standardized mean difference (SMD) were calculated. Results: Results were across 8 studies and 406 patients (85.5% schizophrenia related disorder and 14.5% bipolar disorder) were included (amantadine: 5 trials and 220 patients, memantine: 3 trials and 186 patients). NMDA receptor antagonists (NMDAR-ANTs) as adjunctive therapy were not superior to placebo in overall (SMD=-0.25, CI=-0.72, 0.23, p=0.31, N=6, n=347), positive symptoms (SMD=-0.20, CI=-0.70, 0.31, p=0.44, N=4, n=205), and negative symptoms (SMD=-0.69, CI=-1.65, 0.27, p=0.16, N=4, n=205), and Clinical Global Impression Severity scale (SMD=-0.27, CI=-1.20, 0.65, p=0.56, N=3, n=177). There was also no significant difference in discontinuation rate between NMDAR-ANTs and placebo treatments (all cause: RR=1.23, CI=0.89-1.70, p=0.20, N=8, n=396, side effects: RR=1.86, CI=0.84-4.13, p=0.13, N=6, n=359, inefficacy/worsening psychosis: RR=0.70, CI=0.20-2.38, p=0.56, N=7, n=380). However, memantine was favorable compared with placebo in Mini-Mental State Examination in schizophrenia (SMD=-0.77, CI=-1.27,-0.28, p=0.002, N=3, n=71). While NMDAR-ANTs caused weight loss compared with placebo (SMD=-0.42, CI=-0.73,-0.11, p=0.008, N=3, n=165), amantadine caused more frequent insomnia than placebo (RR=3.83, CI=1.41-10.38, p=0.008, NNH=9, p=0.002, N=2, n=147). Conclusion: Our results indicate that NMDAR-ANTs as adjunctive therapy may improve cognitive function in patients with schizophrenia. Because the included studies were small, a replication study using larger samples is needed. © 2013 Elsevier Ltd.
Yoshida S.,Aichi University
Allergology International | Year: 2011
Pulmonary hypertension (PH) was found to be the primary cause of death in mixed connective tissue disease (MCTD). This led to investigation of the prevalence of PH in other connective tissue diseases (CTD). In 1998, the Ministry of Health and Welfare's MCTD Research Committee revealed complication of PH diagnosed by physicians in 5.02% MCTD patients, 0.90% systemic lupus erythematosus patients, 2.64% systemic sclerosis patients, and 0.56% polymyositis/dermatomyositis patients. These results have been supported by a similar survey performed in North America. As quite a few rheumatologists find right heart catheterization difficult to perform, doppler echocardiography is frequently used for screening and diagnosing PH. The MCTD Research Committee set the revised criteria for MCTD-PH, in which the threshold of estimated pulmonary arterial systolic pressure value for diagnosis of pulmonary arterial hypertension (PAH) is set at 36 mmHg, as proposed by the European Society of Cardiology. Right heart catheterization is strongly recommended for commencing the treatment. Since PH due to thromboembolism can potentially be cured surgically, lung perfusion scintigraphy should be performed for all patients diagnosed with PH. Most CTD-PH are PAH, and since idiopathic PAH (IPAH) patients sometimes have immune disorders, treatment for IPAH may be applicable to CTD-PH. The greatest difference between the treatment strategy for CTDPH and IPAH is the usage of corticosteroids and other immunosuppressants. The MCTD Research Committee updated its therapeutic guidelines for MCTD-PH in 2011. Validation of these guidelines is also needed. © 2011 Japanese Society of Allergology.