Publications by authors named "Rieko Suzuki"

60 Publications

Identification of inhibitors of dengue viral replication using replicon cells expressing secretory luciferase.

Antiviral Res 2019 12 31;172:104643. Epub 2019 Oct 31.

Laboratory of Primate Model, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan; Department of Microbiology, Kanagawa Prefectural Institute of Public Health, Kanagawa, Japan; Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. Electronic address:

Dengue virus (DENV) is the causative agent of dengue fever (DF), dengue haemorrhagic fever (DHF), and dengue shock syndrome (DSS) and continues to be a public health problem in the tropical and subtropical areas. However, there is currently no antiviral treatment for DENV infection. In this study, our aim was to develop a stable reporter replicon cell system that supports constant viral RNA replication in cultured cells. The isolated replicon cells exhibited high levels of luciferase activity in the culture supernatant concomitant with expression of virus-encoded NS1, NS3 and NS5 proteins in the cells. The NS1, NS3 proteins and dsRNA were detected in the replicon cells by immunofluorescence analysis. Furthermore, the anti-DENV inhibitors ribavirin and bromocriptine significantly reduced the luciferase activity in a dose-dependent manner. High-throughput screening with a compound library using the stably-transfected replicon cells showed a Z' factor value of 0.57. Our screening yielded several candidates including one compound that has already shown anti-DENV activity. Taken together, our results demonstrate that this DENV subgenomic replicon cell system expressing a secretory luciferase gene can be useful for the high-throughput screening of anti-DENV compounds and the analysis of the replication mechanism of the DENV RNA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.antiviral.2019.104643DOI Listing
December 2019

Evolutionary Analysis of the and RNA-Dependent RNA Polymerase Regions of Human Norovirus GII.P17-GII.17 in 2013-2017.

Front Microbiol 2019 27;10:2189. Epub 2019 Sep 27.

Graduate School of Health Sciences, Gunma Paz University, Takasaki, Japan.

Human norovirus (HuNoV) GII.P17-GII.17 (Kawasaki2014 variant) reportedly emerged in 2014 and caused gastroenteritis outbreaks worldwide. To clarify the evolution of both and RNA-dependent RNA polymerase () regions of GII.P17-GII.17, we analyzed both global and novel Japanese strains detected during 2013-2017. Time-scaled phylogenetic trees revealed that the ancestral GII.17 region diverged around 1949, while the ancestral GII.P17 region diverged around 2010. The evolutionary rates of the and regions were estimated at ~2.7 × 10 and ~2.3 × 10 substitutions/site/year, respectively. The phylogenetic distances of the region exhibited no overlaps between intra-cluster and inter-cluster peaks in the GII.17 strains, whereas those of the region exhibited a unimodal distribution in the GII.P17 strains. Conformational epitope positions in the VP1 protein of the GII.P17-GII.17 strains were similar, although some substitutions, insertions and deletions had occurred. Strains belonging to the same cluster also harbored substitutions around the binding sites for the histo-blood group antigens of the VP1 protein. Moreover, some amino acid substitutions were estimated to be near the interface between monomers and the active site of the RdRp protein. These results suggest that the GII.P17-GII.17 virus has produced variants with the potential to alter viral antigenicity, host-binding capability, and replication property over the past 10 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2019.02189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777354PMC
September 2019

Stroke during pregnancy and puerperium among Japanese women: a single-center registry.

J Matern Fetal Neonatal Med 2019 Oct 9:1-8. Epub 2019 Oct 9.

Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center , Suita , Japan.

Stroke is one of the major causes of maternal death. This study aimed to analyze the maternal and fetal outcomes of stroke occurred during pregnancy and puerperium. We conducted a retrospective analysis of patients admitted to our perinatology center between 1982 and 2012 with a diagnosis of acute cerebral stroke during pregnancy or within 6 weeks postpartum. Thirty-four patients were registered and all the patients had never been diagnosed as stroke nor detected cerebrovascular abnormalities before the current pregnancies. They were divided into 8 ischemic strokes (ISs) and 26 intracranial hemorrhage group. In the hemorrhage group, there was a spontaneous abortion and two patients chose artificial abortions to avoid rehemorrhage, and there were another three intrauterine fetal deaths (IUFDs) in the acute stage of maternal stroke. More patients in hemorrhage group delivered in preterm than in IS group for the treatment of stroke, 10/23 (43%) 0/8 (0%),  < .05. More patients in hemorrhage group had low Glasgow Coma Scale (GCS) (3-8) than in IS group at the onset of the stroke, 12/26 (46%) 0/8 (0%),  < .05. There were three maternal deaths and 6/23 (26%) were neurologically dependent in hemorrhage group in the chronic stage, whereas 87% were independent in IS group,  < .05. Hemorrhagic stroke was more common etiology of stroke related to pregnancy than IS in this study. Intensive and multidisciplinary care was needed especially in hemorrhagic stroke related to pregnancy as in the hemorrhagic stroke the fetal survival rate was lower, and maternal conscious levels at the onset of the stroke and neurological outcomes in the chronic stage were worse than IS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2019.1675626DOI Listing
October 2019

The detection of house dust mite Dermatophagoides farinae, Der f 2 and Zen-1 allergen-specific immunoglobulin E antibodies in dogs with atopic Dermatitis in Malaysia.

Vet Immunol Immunopathol 2019 Jun 22;212:43-49. Epub 2019 May 22.

Animal Life Science Laboratory, Nippon Zenyaku Kogyo Co., Ltd., Fukushima, 963-0196 Japan.

Canine atopic dermatitis (AD) is a chronic, inflammatory and pruritic allergic skin disease in dogs. House dust mites such as Dermatophagoides farinae are one of the known causative agents for the induction of canine AD worldwide. D. farinae protein Der f 2 is known as an important allergen involved in canine AD and recently, Zen-1 has also been identified as an allergenic protein. There is limited information on the prevalence and role of allergen sensitization to crude D. farinae extract (CDF), Der f 2 and Zen-1 among dogs diagnosed with AD in Malaysia. The aim of this study was to determine the proportion of CDF-, Der f 2- and Zen-1-specific reactive sera among dogs diagnosed with AD in Malaysia using an enzyme-linked immunosorbent assay (ELISA). Serum samples were collected from dogs diagnosed with AD from several veterinary clinics in Malaysia. The canine case records were retrieved and information on signalment, dermatological and non-dermatological histories, clinical presentation, food allergies, and exclusion of ectoparasitic, microbial and fungal skin infections were obtained through a survey form. All serum samples were evaluated to quantify the CDF-, Der f 2- and Zen-1-specific immunoglobulin E (IgE) levels. A total of 24.6%, 48.4% and 29.8% of dogs diagnosed with AD were positive for CDF-, Der f 2- and Zen-1-specific IgE, respectively. These results suggest that CDF-, Der f 2- and Zen-1 are important allergens that can contribute to AD in dogs in Malaysia, and serological testing can be performed to provide additional treatment options involving specific immunotherapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vetimm.2019.05.002DOI Listing
June 2019

Baseline Carotid Intima-Media Thickness and Stroke Recurrence During Secondary Prevention With Pravastatin.

Stroke 2019 06 30;50(6):1586-1589. Epub 2019 Apr 30.

Department of Neurology, Sakai City Medical Center, Japan (M.M.).

Background and Purpose- As a prespecified post hoc analysis of the J-STARS (Japan Statin Treatment Against Recurrent Stroke) Echo Study, the 5-year stroke recurrence rate according to the baseline mean carotid intima-media thickness (IMT) with and without pravastatin treatment was investigated. Methods- Patients were randomly assigned to receive pravastatin 10 mg/day (pravastatin group) or control group (nonstatin treatment; 1:1) for 5 years. Baseline mean IMT of the common carotid artery was measured by ultrasonography. Cox proportional hazards models were used to investigate whether the stroke (any ischemic stroke, atherothrombotic brain infarction, or lacunar infarction) recurrence rate was different according to tertiles of baseline mean IMT. Results- A total of 793 patients, including 388 in the pravastatin group and 405 in the control group, were investigated. In the control group, Cox proportional hazards models showed that participants in the highest tertile IMT group (≥0.931 mm) had a higher rate of atherothrombotic brain infarction than those in the lowest tertile IMT group (<0.812 mm; [hazard ratio, 9.08; 95% CI, 1.15-71.43]). Patients in the pravastatin group had a lower risk of atherothrombotic brain infarction than those in the control group only in the highest tertile IMT group by the log-rank test ( P value=0.045). Conclusions- Long-term pravastatin administration may prevent the occurrence of atherothrombotic brain infarction in noncardioembolic infarction patients with the highest tertile IMT. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00361530.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.119.024968DOI Listing
June 2019

Stearoyl-CoA desaturase-1 is required for flavivirus RNA replication.

Antiviral Res 2019 05 7;165:42-46. Epub 2019 Mar 7.

Kanagawa Prefectural Institute of Public Health, Kanagawa, Japan.

Dengue virus (DENV) is the most prevalent human arthropod-borne virus and causes severe problems worldwide, mainly in tropical and sub-tropical regions. However, there is no specific antiviral drug against DENV infection. We and others recently reported that stearoyl-CoA desaturase-1 (SCD1) inhibitor showed potent suppression of hepatitis C virus replication. In this study, we examined the impact of SCD1 on DENV replication. We found that SCD1 inhibitors (MK8245 and #1716) dramatically suppressed DENV replication in a dose-dependent manner without cytotoxicity. This anti-DENV efficacy was observed against all four DENV serotypes and other flaviviruses, including Zika virus and Japanese encephalitis virus. A subgenomic replicon system of DENV was used to confirm that SCD1 inhibitor suppressed viral RNA replication. Interestingly, exogenous supplementation of unsaturated fatty acids resulted in recovery of the DENV titer even in the presence of SCD1 inhibitor, suggesting that fatty acid biosynthesis contributes to DENV genome replication. These findings indicate that SCD1 is a novel host factor required for DENV replication, and SCD1 inhibitor is a potential candidate for treating dengue fever.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.antiviral.2019.03.002DOI Listing
May 2019

Subcutaneous Heparin Therapy for Patients with Cancer-Associated Stroke.

J Stroke Cerebrovasc Dis 2019 Feb 5;28(2):399-404. Epub 2018 Nov 5.

Stroke Center, Kyorin University, Mitaka, Tokyo, Japan; Department of Stroke and Cerebrovascular Medicine, Kyorin University, Mitaka, Tokyo, Japan.

Background: Anticoagulation therapy, particularly subcutaneous heparin therapy, is recommended for cancer-associated thrombosis. However, not starting or discontinuing anticoagulation was not rare. The aim of the present study was to examine the practical issues related to anticoagulation therapy and effects of subcutaneous heparin therapy for cancer-associated stroke.

Methods: Patients with cancer-associated stroke in our stroke center between October 2014 and August 2017 who were diagnosed as having acute ischemic stroke based on diffusion-weighted imaging were retrospectively enrolled. Baseline clinical characteristics, heparin injection, reasons for no subcutaneous heparin therapy, and clinical outcomes were collected.

Results: A total of 59 patients with cancer-associated stroke (75 ± 10 years old, male 42%) were enrolled. Lung cancer was the most frequently observed cancer (n = 17, 29%), followed by gastric cancer (n = 8, 14%) and pancreatic cancer (n = 8, 14%). Of the 19 patients (32%) who underwent subcutaneous heparin therapy, it was discontinued in 9 (47%), mainly because of patients' medical conditions (deterioration of cancer or hemorrhagic complication). Ten patients with long-term subcutaneous heparin therapy did not have stroke recurrence. In contrast, among nine patients who discontinued subcutaneous heparin therapy, three (33%) had recurrence of ischemic stroke. Of the 40 patients without subcutaneous heparin therapy, the main reasons for no subcutaneous heparin therapy were the patients' medical conditions (n = 22, 55%).

Conclusions: Although subcutaneous heparin therapy was given to only one third of cancer-associated stroke patients, long-term subcutaneous heparin therapy might prevent recurrence of cancer-associated stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.10.012DOI Listing
February 2019

Frontal activity measured by near-infrared spectroscopy in patients taking different atypical antipsychotic drugs: A cross-sectional study.

Psychiatry Res Neuroimaging 2018 03 27;273:42-45. Epub 2017 Dec 27.

Department of Neuropsychiatry, Fukushima Medical University, Fukushima, Japan.

Using near-infrared spectroscopy, we examined changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the frontal lobe during a verbal fluency task in 20 patients with schizophrenia (10 patients each receiving olanzapine [OLZ] and risperidone [RIS]) and 10 healthy controls. We found that [oxy-Hb] levels in the prefrontal region were higher in the patients receiving OLZ than in those receiving RIS. These results suggest that antipsychotic drugs have different effects on cerebral hemodynamic patterns, which may reflect frontal lobe function. Further studies with a larger sample size are needed to verify our preliminary findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pscychresns.2017.12.003DOI Listing
March 2018

Evaluation of Brain Activity Using Near-infrared Spectroscopy in Inflammatory Bowel Disease Patients.

Sci Rep 2018 01 10;8(1):402. Epub 2018 Jan 10.

Departments of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Depression is implicated as a risk factor for the recurrence of inflammatory bowel disease (IBD). Near-infrared spectroscopy (NIRS) and brain-derived neurotrophic factor (BDNF) are useful tools for evaluation of brain activity and a depressive state, respectively. The aim of this study was to clarify the association between brain activity or depressive symptoms and IBD using NIRS and BDNF. This study included 36 ulcerative colitis (UC) patients, 32 Crohn's disease (CD) patients, and 17 healthy controls (HC). Center for Epidemiologic Studies Depression Scale (CES-D) scores were determined, NIRS was performed, and serum BDNF levels were measured in all subjects. NIRS showed that the mean oxygenated hemoglobin concentration was significantly lower in the frontal lobe in the UC group than in the HC group (HC 167 ± 106 vs. UC 83.1 ± 85.3, p < 0.05). No significant difference was seen between the HC and CD groups. There were also no significant differences in CED-D scores and BDNF levels among the groups. Changes in the NIRS values of the UC group may indicate decreased brain activity and a fundamental difference between UC and CD, which are often lumped together as two types of IBD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-18897-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762642PMC
January 2018

Long-Term Effect of Pravastatin on Carotid Intima-Media Complex Thickness: The J-STARS Echo Study (Japan Statin Treatment Against Recurrent Stroke).

Stroke 2018 01 30;49(1):107-113. Epub 2017 Nov 30.

From the Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (M.K., K.T., K.M., R.S.); Department of Cerebrovascular Medicine and Neurology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan (M.Y.); Clinical & Translational Research Center, Kobe University Hospital, Japan (Y.N.); Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Japan (S.A., T.N., N.H., T.O., H.M., M.M.); Foundation for Biomedical Research and Innovation, Translational Research Informatics Center, Kobe, Japan (T.K.); Division of Biostatistics and Clinical Epidemiology, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Japan (H.O.); Department of Neurosurgery and Stroke Center, Nakamura Memorial Hospital, Sapporo, Japan (K.K.); Stroke Center, Kinki University, Osakasayama, Japan (T.O.); Department of Neurology, Tokyo Women's Medical University, Japan (K.K.); International University of Health and Welfare, Center for Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center, Tokyo, Japan (S.U.); and Japan Community Healthcare Organization Hoshigaoka Medical Center, Hirakata (M.M.).

Background And Purpose: The effect of statins on progression of carotid intima-media complex thickness (IMT) has been shown exclusively in nonstroke Western patients. This study aimed to determine the effect of low-dose pravastatin on carotid IMT in Japanese patients with noncardioembolic ischemic stroke.

Methods: This is a substudy of the J-STARS trial (Japan Statin Treatment Against Recurrent Stroke), a multicenter, randomized, open-label, parallel-group trial to examine whether pravastatin reduces stroke recurrence. Patients were randomized to receive pravastatin (10 mg daily, usual dose in Japan; pravastatin group) or not to receive any statins (control group). The primary outcome was IMT change of the common carotid artery for a 5-year observation period. IMT change was compared using mixed-effects models for repeated measures.

Results: Of 864 patients registered in this substudy, 71 without baseline ultrasonography were excluded, and 388 were randomly assigned to the pravastatin group and 405 to the control group. Baseline characteristics were not significantly different, except National Institutes of Health Stroke Scale scores (median, 0 [interquartile range, 0-2] versus 1 [interquartile range, 0-2]; =0.019) between the 2 groups. Baseline IMT (mean±SD) was 0.887±0.155 mm in the pravastatin group and 0.887±0.152 mm in the control group (=0.99). The annual change in the IMT at 5-year visit was significantly reduced in the pravastatin group as compared with that in the control group (0.021±0.116 versus 0.040±0.118 mm; =0.010).

Conclusions: The usual Japanese dose of pravastatin significantly reduced the progression of carotid IMT at 5 years in patients with noncardioembolic stroke.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00361530.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.117.018387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753816PMC
January 2018

Factors Associated with Intima-Media Complex Thickness of the Common Carotid Artery in Japanese Noncardioembolic Stroke Patients with Hyperlipidemia: The J-STARS Echo Study.

J Atheroscler Thromb 2018 Apr 8;25(4):359-373. Epub 2017 Nov 8.

Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences.

Aims: There may be ethnic differences in carotid atherosclerosis and its contributing factors between Asian and other populations. The purpose of this study was to examine intima-media complex thickness (IMT) of the carotid artery and associated clinical factors in Japanese stroke patients with hyperlipidemia from a cohort of the Japan Statin Treatment Against Recurrent Stroke Echo Study.

Methods: Patients with hyperlipidemia, not on statins, who developed noncardioembolic ischemic stroke were included in this study. Mean IMT and maximum IMT of the distal wall of the common carotid artery were centrally measured using carotid ultrasonography. Significant factors related to mean IMT and maximum IMT were examined using multivariable analysis.

Results: In 793 studied patients, mean IMT was 0.89±0.15 mm and maximum IMT was 1.19±0.32 mm.Age (per 10 years, parameter estimate=0.044, p<0.001), smoking (0.022, p=0.004), category of blood pressure (0.022, p=0.006), HDL cholesterol (per 10 mg/dl, -0.009, p=0.008), and diabetes mellitus (0.033, p=0.010) were independently associated with mean IMT. Age (per 10 years, 0.076, p<0.001), smoking (0.053, p=0.001), HDL cholesterol (-0.016, p=0.036), and diabetes mellitus (0.084, p=0.002) were independently associated with maximum IMT.

Conclusion: Baseline mean and maximum values of carotid IMT in Japanese noncardioembolic stroke patients with hyperlipidemia were 0.89±0.15 mm and 1.19±0.32 mm, respectively, which were similar to those previously reported from Western countries. Age, smoking, hypertension, HDL cholesterol, and diabetes mellitus were associated with mean IMT, and those, except for hypertension, were associated with maximum IMT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5551/jat.41533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906189PMC
April 2018

Dynamic changes in near-infrared spectroscopy (NIRS) findings in first-episode schizophrenia: a case report.

Fukushima J Med Sci 2017 Apr 15;63(1):28-31. Epub 2017 Apr 15.

Department of Neuropsychiatry, Fukushima Medical University School of Medicine.

The clinical course of schizophrenia is characterized by recurrence and chronicity and has a large burden on society. Nevertheless, diagnosis of schizophrenia is based only on distinctive symptoms and the disease course. Near-infrared spectroscopy (NIRS) is a useful method for measuring changes in the hemoglobin concentration in the cortical surface area and reflects brain function. We measured NIRS four times during the clinical course in a patient with first-episode schizophrenia.A 17-year-old woman admitted to our hospital because of hallucinations, delusions and appetite loss. After treatment with low-dose antipsychotics, NIRS findings showed a prompt increase in the cerebral blood volume in the frontal region. On the basis of the clinical course of this patient, we introduce a new point of view, namely, that NIRS findings may be useful as a state marker that indicates the severity of schizophrenia in some cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5387/fms.2016-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476820PMC
April 2017

Analysis of Factors Associated with Progression and Long-Term Outcomes of Penetrating Artery Territory Infarction: A Retrospective Study.

J Stroke Cerebrovasc Dis 2016 Aug 16;25(8):1952-9. Epub 2016 May 16.

Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.

Background: Patients with penetrating artery territory infarction occasionally show progressive motor deficits during the acute stage with poor prognosis. Predictive indices or medical therapies for suppressing the symptomatic progression (SP) of penetrating artery infarction have not been established. In this study, we investigated SP-related clinical factors and functional outcomes, specifically improvement 3 months post ictus in patients with penetrating artery infarction.

Methods: We retrospectively examined acute stroke patients with penetrating artery infarction admitted at 7 collaborative hospitals. SP was defined as an increase by 1 point or higher in the National Institutes of Health Stroke Scale score. Functional improvement was assessed based on the modified Rankin Scale at 3 months. The influence of factors, such as patient characteristics, clinical data, medical treatment during the acute stage and on SP, and functional improvement was statistically analyzed.

Results: Four hundred eighty-eight patients (310 men; mean age, 70 years) were examined. Sixty-eight patients (14%) exhibited SP. Multivariate logistic regression analysis revealed that higher hemoglobin A1c (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.10-1.55), body mass index (BMI; OR, .85; 95% CI, .77-.94), and systolic blood pressure on admission (OR, 1.63; 95% CI, 1.19-2.25) were independent predictors of SP in penetrating artery infarction. Dual antiplatelet therapy (DAPT; OR, 3.48; 95% CI, 1.52-8.38) independently influenced functional improvement.

Conclusions: Initial high blood pressure, diabetes, and low BMI on admission were associated with early progression of penetrating artery infarction. DAPT during the acute stage may contribute to functional improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.04.007DOI Listing
August 2016

Development of Interstitial Lung Disease after Initiation of Apixaban Anticoagulation Therapy.

J Stroke Cerebrovasc Dis 2016 Jul 15;25(7):1767-1769. Epub 2016 Apr 15.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.

Background: Nonvitamin K antagonist oral anticoagulants may cause interstitial lung disease (ILD) similar to that seen for other cardiovascular drugs. The aim of this study was to determine trends and medical conditions associated with ILD in patients taking apixaban.

Methods: A single-center observational survey conducted between February 2013 and May 2015 examined patients who developed ILD after initiation of apixaban administration.

Results: Chest computed tomography showed that 4 (~.45%) out of approximately 870 apixaban users developed ILD. All patients were elderly Japanese men with decreased creatinine clearance who had nonvalvular atrial fibrillation. Three of the four were confirmed smokers, whereas three had a history of lung disease. Dyspnea occurred during the initial week after starting apixaban administration in 3 patients and at 90 days in 1 patient. All patients underwent methylprednisolone pulse therapy, with three requiring mechanical ventilation. Although 2 patients recovered, the other two died of respiratory failure.

Conclusions: Development of ILD during anticoagulation with apixaban is not rare. When apixaban is administered in elderly high-risk patients, subjects need to be carefully monitored for respiratory symptoms. As drug-induced ILD is often reported in Japan, further studies that clarify if these types of cases are common in countries other than Japan will also need to be undertaken.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.03.036DOI Listing
July 2016

A preliminary ex vivo study of 3D ultrasonography of aortic atherosclerosis using autopsied aorta.

Int J Stroke 2016 10 30;11(7):NP74. Epub 2016 Mar 30.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1747493016641957DOI Listing
October 2016

Optimal Peak Systolic Velocity Thresholds for Predicting Internal Carotid Artery Stenosis Greater than or Equal to 50%, 60%, 70%, and 80%.

J Stroke Cerebrovasc Dis 2016 04 2;25(4):921-6. Epub 2016 Feb 2.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.

Background: We aimed to determine the optimal peak systolic velocity (PSV) thresholds for predicting ≥50%, ≥60%, ≥70%, and ≥80% internal carotid artery (ICA) stenosis.

Methods: Patients who underwent both carotid ultrasonography and cerebral angiography during hospitalization were consecutively and retrospectively enrolled. The degree of ICA stenosis was calculated using the North American Symptomatic Carotid Endarterectomy Trial method on cerebral angiography. The optimal PSV thresholds for predicting ≥50%, ≥60%, ≥70%, and ≥80% ICA stenosis were determined using receiver operating characteristic curves and the Youden index.

Results: A total of 127 ICAs were analyzed. The optimal PSV thresholds for predicting ≥50%, ≥60%, ≥70%, and ≥80% ICA stenosis were 130 cm/s (sensitivity, 95%; specificity, 85%; positive predictive value [PPV], 75%; negative predictive value [NPV], 97%; overall accuracy, 88%), 160 cm/s (sensitivity, 91%; specificity, 94%; PPV, 83%; NPV, 97%; overall accuracy, 93%), 200 cm/s (sensitivity, 96%; specificity, 95%; PPV, 83%; NPV, 99%; overall accuracy, 95%), and 270 cm/s (sensitivity, 89%; specificity, 94%; PPV, 74%; NPV, 98%; overall accuracy, 94%), respectively.

Conclusions: The optimal PSV thresholds for predicting ≥50%, ≥60%, ≥70%, and ≥80% ICA stenosis were 130 cm/s, 160 cm/s, 200 cm/s, and 270 cm/s, respectively. All of them had high diagnostic accuracies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.12.021DOI Listing
April 2016

Molecular Evolution of the Capsid Gene in Norovirus Genogroup I.

Sci Rep 2015 Sep 4;5:13806. Epub 2015 Sep 4.

Department of Molecular Biodefence Research, Yokohama City University Graduate School of Medicine, Yokohama-shi, Kanagawa 236-0004, Japan.

We studied the molecular evolution of the capsid gene in all genotypes (genotypes 1-9) of human norovirus (NoV) genogroup I. The evolutionary time scale and rate were estimated by the Bayesian Markov chain Monte Carlo (MCMC) method. We also performed selective pressure analysis and B-cell linear epitope prediction in the deduced NoV GI capsid protein. Furthermore, we analysed the effective population size of the virus using Bayesian skyline plot (BSP) analysis. A phylogenetic tree by MCMC showed that NoV GI diverged from the common ancestor of NoV GII, GIII, and GIV approximately 2,800 years ago with rapid evolution (about 10(-3) substitutions/site/year). Some positive selection sites and over 400 negative selection sites were estimated in the deduced capsid protein. Many epitopes were estimated in the deduced virus capsid proteins. An epitope of GI.1 may be associated with histo-blood group antigen binding sites (Ser377, Pro378, and Ser380). Moreover, BSP suggested that the adaptation of NoV GI strains to humans was affected by natural selection. The results suggested that NoV GI strains evolved rapidly and date back to many years ago. Additionally, the virus may have undergone locally affected natural selection in the host resulting in its adaptation to humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep13806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559769PMC
September 2015

Transient ischemic attack clinic in an urban area of Japan.

Int J Stroke 2015 Jul;10(5):E43

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijs.12503DOI Listing
July 2015

Early Stroke Risk after Transient Ischemic Attack in Patients without Large-Artery Disease or Atrial Fibrillation.

J Stroke Cerebrovasc Dis 2015 Jul 23;24(7):1656-61. Epub 2015 Apr 23.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.

Background: Patients with transient ischemic attack (TIA) without large-artery disease (LAD) or atrial fibrillation (AF) on admission may be at higher risk of stroke than previously thought. The aim of this study was to investigate early stroke risk and its predictors in such patients.

Methods: We studied 410 TIA patients admitted to our institute within 48 hours of onset. Urgent etiological workup revealed that 210 patients had neither symptomatic LAD nor AF. The outcome measure was the stroke occurrence within 7 days after admission.

Results: Stroke occurred within 7 days in 15 patients, 7.1% of patients without LAD or AF and 6.5% of those with LAD or AF, showing no statistical difference between the 2 groups. Twelve of the 15 patients were diagnosed with small-vessel disease as the stroke etiology. In multivariable regression analysis, motor lacunar symptoms (odds ratio [OR], 5.7; 95% confidence interval [CI], 1.4-41.1), high systolic blood pressure on admission of 183 mm Hg or greater (OR, 15.3; 95% CI, 3.8-80.2), and positive diffusion-weighted imaging findings (OR, 6.1; 95% CI, 1.6-28.1) were independent predictors for the stroke occurrence within 7 days in patients without LAD or AF.

Conclusions: TIA patients should be cautiously managed, even when neither LAD nor AF are identified by urgent workup. Clinical findings as motor lacunar symptom or high admission blood pressure, besides diffusion-weighted imaging findings, may be helpful to predict early stroke in such patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.03.039DOI Listing
July 2015

Factors associated with unfavorable outcome in minor ischemic stroke.

Neurology 2014 Jul 6;83(2):174-81. Epub 2014 Jun 6.

From the Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.

Objectives: The purpose of this study was to elucidate the factors that correlate with unfavorable outcomes and to develop a simple validated model for assessing risk of unfavorable outcomes in patients with minor ischemic stroke.

Methods: The derivation cohort included 1,313 patients hospitalized within 72 hours after onset with an initial NIH Stroke Scale score of 0 to 3 enrolled in a prospective, multicenter, observational study. Unfavorable outcome was defined as dependency (modified Rankin Scale score of 3-5) or death at 90 days. The predictive values of factors related to unfavorable outcome were evaluated. External validation was performed in 879 patients from a single-center stroke registry.

Results: In the derivation cohort, a total of 203 patients (15%) had unfavorable outcomes. On multivariable analysis, women (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.30-2.94), age ≥72 years (OR 2.80, 95% CI 1.83-4.36), intra/extracranial vascular occlusive lesion (OR 2.80, 95% CI 1.82-4.28), leg weakness (OR 1.72, 95% CI 1.06-2.82), and extinction/inattention (OR 5.55, 95% CI 1.30-21.71) were independently associated with unfavorable outcome. Patients having both a vascular lesion and either leg weakness or extinction/inattention showed 4.63 (95% CI 2.23-9.33) times the risk of unfavorable outcome compared with those having neither. In the validation cohort, the risk was similar, at 3.77 (95% CI 1.64-8.37).

Conclusions: Intra- and extracranial vascular imaging, NIH Stroke Scale items such as leg weakness and extinction/inattention, and their combination, as well as female sex and advanced age, may be useful for predicting unfavorable outcomes in patients with minor stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000000572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117175PMC
July 2014

A questionnaire survey of general practitioners in Japan in relation to management of transient ischemic attack.

Int J Stroke 2014 Jun;9(4):E16-7

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijs.12266DOI Listing
June 2014

Three-dimensional analysis of the left atrial appendage for detecting paroxysmal atrial fibrillation in acute ischemic stroke.

Int J Stroke 2014 Dec 13;9(8):1045-51. Epub 2014 Mar 13.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.

Background: Atrial fibrillation impairs left atrial appendage function and the thrombus formation in the left atrial appendage is a major cause of cardioembolic stroke.

Aims: To evaluate the association between the volume of the left atrial appendage measured by real-time three-dimensional transesophageal echocardiography and presence of paroxysmal atrial fibrillation in patients with cerebral infarction or transient ischemic attack.

Methods: Real-time three-dimensional transesophageal echocardiography was performed to measure left atrial appendage end-diastolic and end-systolic volumes to calculate left atrial appendage ejection fraction. Patients with normal sinus rhythm at the time of real-time three-dimensional transesophageal echocardiography were divided into groups with and without paroxysmal atrial fibrillation. Volumetric data were corrected with the body surface area.

Results: Of 146 patients registered, 102 (29 women, 72·2 ± 10·7 years) were normal sinus rhythm at the examination. In 23 patients with paroxysmal atrial fibrillation, left atrial appendage end-diastolic volume (4·78 ± 3·00 ml/m(2) vs. 3·14 ± 2·04 ml/m(2), P = 0·003) and end-systolic volume (3·10 ± 2·47 ml/m(2) vs. 1·39 ± 1·56 ml/m(2), P < 0·001) were larger and left atrial appendage ejection fraction (37·3 ± 19·1% vs. 57·1 ± 17·5%, P < 0·001) was lower than in the other 79 patients without paroxysmal atrial fibrillation. The optimal cutoff for left atrial appendage peak flow velocity to predict paroxysmal atrial fibrillation was 39·0 cm/s (sensitivity, 54·6%; specificity, 89·7%; c-statistic, 0·762). The cutoffs for left atrial appendage end-diastolic volume, end-systolic volume, and ejection fraction were 4·52 ml/m(2) (sensitivity, 47·8%; specificity, 82·3%; c-statistic, 0·694), 1·26 ml/m(2) (sensitivity, 91·3%; specificity, 60·3%; c-statistic, 0·806), and 47·9% (sensitivity, 78·3%; specificity, 74·7%; c-statistic, 0·774), respectively. In multivariate analysis, all these parameters were independently associated with paroxysmal atrial fibrillation after adjusting for sex, age, diabetes mellitus, and previous stroke.

Conclusions: Left atrial appendage volumetric analysis by real-time three-dimensional transesophageal echocardiography is a promising method for detecting paroxysmal atrial fibrillation in acute cerebral infarction or transient ischemic attack.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijs.12268DOI Listing
December 2014

Complex visual hallucinations as the sole manifestation of symptomatic temporo-occipital lobe epilepsy due to old intracerebral hemorrhage.

Seizure 2014 Mar 9;23(3):244-6. Epub 2013 Nov 9.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2013.11.001DOI Listing
March 2014

Neurologic improvement without angiographic improvement after antithyroid therapy in a patient with Moyamoya syndrome.

J Stroke Cerebrovasc Dis 2014 May-Jun;23(5):1256-8. Epub 2013 Oct 8.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.

Moyamoya disease with special complications, including Graves' disease, is called as moyamoya syndrome. A 22-year-old Japanese woman had left middle cerebral artery (MCA) territory infarction complicated with Graves' disease. She had right-sided hemiparesis that deteriorated on day 8 with the infarct growth and thyrotoxicosis. On angiogram, the left MCA was occluded at the origin without moyamoya vessels. Positron emission tomography (PET) revealed misery-perfusion phenomenon in the left MCA territory. After initiation of the antithyroid therapy, her hemiparesis became milder. Seventeen months later, her thyroid function was normalized and net-like collateral moyamoya vessels proliferated in the left MCA territory. Misery-perfusion phenomenon persisted on PET. This report is unique in the point of neurologic recovery of the moyamoya patient right after initiation of antithyroid medication without radiological improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.08.025DOI Listing
January 2015

Anterior inferior cerebellar artery territorial infarction caused by vertebral artery dissection.

Cerebrovasc Dis 2013 10;35(6):592. Epub 2013 Jul 10.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000350729DOI Listing
March 2014

Decitabine, a DNA methyltransferase inhibitor, reduces P-glycoprotein mRNA and protein expressions and increases drug sensitivity in drug-resistant MOLT4 and Jurkat cell lines.

Anticancer Res 2012 Oct;32(10):4439-44

Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.

Multidrug resistance (MDR) is a major clinical obstacle in the treatment of several cancers including hematological malignancies and solid tumors. The ATP-binding cassette transporter B1 (ABCB1) gene and its product, P-glycoprotein (P-gp), is one molecule that is involved in drug resistance. Here we report on the effect of decitabine (5-aza-2'-deoxycytidine), an inhibitor of DNA methyltransferase, on ABCB1 mRNA and P-gp expressions in drug-resistant MOLT4 and Jurkat cells. We found that decitabine treatment reduced ABCB1 mRNA and P-gp expressions in MOLT4/daunorubicin-resistant and Jurkat/doxorubicin-resistant cells. The decrease in the expression of ABCB1 mRNA and P-gp was accompanied by increased sensitivity to anticancer drugs in both drug-resistant cell lines. Our data suggest that DNA methylation is one of the mechanisms underlying ABCB1/P-gp overexpression in drug-resistant hematopoietic cell lines. The modulation of ABCB1/P-gp by DNA methylation inhibitors may be an effective strategy to overcome P-gp-related drug resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2012

TLS-CHOP represses miR-486 expression, inducing upregulation of a metastasis regulator PAI-1 in human myxoid liposarcoma.

Biochem Biophys Res Commun 2012 Oct 18;427(2):355-60. Epub 2012 Sep 18.

Department of Molecular Pathology, Tokyo Medical University, Tokyo 160-8402, Japan.

Myxoid liposarcomas (MLSs) are characterized by t(12;16)(q13;p11) translocation and expression of TLS-CHOP chimeric oncoprotein. However, the molecular functions of TLS-CHOP have not been fully understood. On the other hand, microRNAs (miRNAs) comprise an abundant class of endogenous small non-coding RNAs that negatively regulate the expression of their target genes, and are involved in many biological processes. It is now evident that dysregulation of miRNAs is an important step in the development of many cancers. To our knowledge, however, there have been no reports of the miRNAs involved in MLS tumorigenesis and development. In this study, we have found that miR-486 expression was repressed in TLS-CHOP-expressed NIH3T3 fibroblasts and MLS tissues, and exogenous overexpression of miR-486 repressed growth of MLS cells. Thus, downregulation of miR-486 may be an important process for MLS. In addition, we have identified plasminogen activator inhibitor-1 (PAI-1) as a novel target gene of miR-486. PAI-1 is a unique type of serine protease inhibitor and is known to be one of the key regulators of tumor invasion and metastasis. Furthermore, knockdown of PAI-1 by a specific small interfering RNA (siRNA) inhibited growth of MLS cells, suggesting that increased expression of PAI-1 by miR-486 repression is critical for survival of MLS cells. Collectively, these results suggest a novel essential molecular mechanism that TLS-CHOP activates PAI-1 expression by repression of miR-486 expression in MLS tumorigenesis and development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2012.09.063DOI Listing
October 2012

[Detection of parechovirus in infectious gastroenteritis patients from Kanagawa Prefecture Region. Fecal specimens sent from the pediatric sentinel clinics from April 2008 to March 2011].

Kansenshogaku Zasshi 2012 Jul;86(4):393-9

Biology Division, Kanagawa Prefectural Institute of Public Health.

To clarify the causative viruses of infectious gastroenteritis, fecal specimens were sent from the pediatric sentinel clinic in Kanagawa Prefecture except for Kawasaki City, Yokohama City, Yokosuka City, Sagamihara City, and Fujisawa City. About 50% of fecal specimens were not negative for causative viruses. A total of 374 fecal specimens which were known to be negative for rotavirus, adenovirus, norovirus, sapovirus, and astrovirus were tested for human parechovirus (HPeV). HPeVs VP1 genes were detected in 15 samples from 374 fecal specimens which were tested from April 2008 to March 2011. Sequencing analysis of a 800-nt portion of the HPeV VP1 gene of these 8 strains and 7 specimens from April 2008 to March 2011 showed that one specimen in Septenber 2008 was classified as HPeV4 and 14 of the others were classified as HPeV1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11150/kansenshogakuzasshi.86.393DOI Listing
July 2012

Common carotid artery dissection caused by a frontal thrust in Kendo (Japanese swordsmanship).

Circulation 2012 May;125(17):e617-9

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.111.066472DOI Listing
May 2012

Trichoderma matsushimae and T. aeroaquaticum: two aero-aquatic species with Pseudaegerita-like propagules.

Mycologia 2012 Sep-Oct;104(5):1109-20. Epub 2012 Apr 11.

National Institute of Technology and Evaluation, Kisarazu, Chiba, Japan.

Four isolates tentatively identified as Pseudaegerita matsushimae on the basis of the morphology of bulbil-like propagules were collected from substrates submerged in water in Thailand and Japan. In culture studies the two Thai isolates were found to produce phialoconidia on conidiogenous cells and phialoconidiophores whose morphology was similar to that of Trichoderma. Phylogenetic analysis based on D1/D2 regions of LSU rDNA sequences showed that the four isolates were nested in Hypocrea/Trichoderma (Hypocreales) while P. corticalis, the type species of Pseudaegerita, belongs to Hyaloscypha (Helotiales). Preliminary analysis by ISTH Web tools based on 5.8S-ITS rDNA and phylogenetic analysis based on rpb2 and tef1-int4 genes showed that the isolates have specific sequences of Trichoderma (anchors 1-5) and belong to the Hamatum clade but they grouped apart from any known species of Trichoderma. The sequences of the tef1-int4 gene, which were amplified from the authentic specimen of P. matsushimae (IMI 266915), also showed that it belongs to the Hamatum clade closely clustering with T. yunnanense but separate from our four isolates. The morphology of P. matsushimae (IMI 266915), especially the sizes of phialides and phialoconidia, were different from T. yunnanense. Thus, we conclude that IMI 266915 and our isolates are to be assigned to two different species in the Hamatum clade of Trichoderma, although both species have similar morphology of bulbils and phialoconidia. Morphology and molecular data revealed that P. matsushimae should be assigned to the genus Trichoderma as T. matsushimae and the Thai and Japanese isolates are placed in T. aeroaquaticum sp. nov. This finding supports the interpretation that aero-aquatic fungi have evolved from terrestrial fungi. We assume that these fungi probably were derived from typically soil-inhabiting species of Trichoderma; an adaptation to aquatic environments is shown by formation of bulbil-like propagules floating on water.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3852/11-253DOI Listing
November 2012