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Find video protocols related to scientific articles indexed in Pubmed.
Expanding the Regulatory Network Governed by the ECF-family Sigma factor ?H in Corynebacterium glutamicum.
J. Bacteriol.
PUBLISHED: 11-19-2014
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The extracytoplasmic function sigma factor ?(H) is responsible for heat and oxidative stress response in Corynebacterium glutamicum. Due to the hierarchical nature of the regulatory network, previous transcriptome analyses have not been able to discriminate between direct and indirect targets of ?(H). Here, we determined the direct genome-wide targets of ?(H) by ChIP-chip analysis using a deletion mutant of rshA, encoding an anti-? factor of ?(H). Seventy-five ?(H)-dependent promoters, including 39 new ones, were identified. ?(H)-dependent, heat-inducible transcripts for several of the new targets, including ilvD encoding a labile Fe-S cluster enzyme dihydroxy-acid dehydratase, were detected and their 5' -ends were mapped to the ?(H)-dependent promoters identified. Interestingly, functional internal ?(H)-dependent promoters were found in operon-like gene clusters involved in the pentose phosphate pathway, riboflavin biosynthesis, and Zn uptake. Accordingly, deletion of rshA resulted in hyperproduction of riboflavin and affected expression of Zn-responsive genes possibly through intracellular Zn overload, indicating new physiological roles of ?(H). Furthermore, sigA encoding the primary ? factor was identified as a new target of ?(H). Reporter assays demonstrated that the ?(H)-dependent promoter upstream of sigA was highly heat-inducible but much weaker than the known ?(A)-dependent one. Our ChIP-chip analysis also detected the ?(H)-dependent promoters upstream of rshA within the sigH-rshA operon, and of sigB encoding a group 2 ? factor, supporting the previous findings of their ?(H)-dependent expression. Taken together, these results offered an additional layer of the sigma factor regulatory network in C. glutamicum.
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Spontaneous heparin-induced thrombocytopenia syndrome without any proximate heparin exposure, infection, or inflammatory condition: Atypical clinical features with heparin-dependent platelet activating antibodies.
Platelets
PUBLISHED: 11-11-2014
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Abstract Recent studies suggest that a thromboembolic disorder resembling heparin-induced thrombocytopenia (HIT), so-called spontaneous HIT syndrome, can occur in patients without any history of heparin exposure. It is likely due to anti-platelet factor 4 (PF4)/polyanion antibodies induced by other polyanions, such as bacterial surfaces and nucleic acids. We describe an atypical case of spontaneous HIT syndrome. A 70-year-old man suddenly presented with acute cerebral sinus thrombosis (CST). Soon after the initiation of unfractionated heparin (UFH) for the treatment of CST, his platelet count fell precipitously and he developed deep vein thrombosis, a clinical picture consistent with rapid-onset HIT but without any proximate episodes of heparin exposure, infection, trauma, surgery, or other acute illness. Antigen assays and a washed platelet activation assay indicated that the patient already possessed anti-PF4/heparin IgG antibodies with heparin-dependent platelet activation properties on admission. Cessation of UFH and initiation of argatroban resulted in prompt recovery of his platelet count without further thromboembolic events. We identified two similar cases in the literature. However, these patients do not meet the recently proposed criteria for spontaneous HIT syndrome. Even in atypical cases, however, inappropriate or delayed diagnosis of HIT appears to be associated with worse outcomes. We propose that these atypical cases should be included in the category of spontaneous HIT syndrome.
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Consciousness level and off-hour admission affect discharge outcome of acute stroke patients: a J-ASPECT study.
J Am Heart Assoc
PUBLISHED: 10-23-2014
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Poor outcomes have been reported for stroke patients admitted outside of regular working hours. However, few studies have adjusted for case severity. In this nationwide assessment, we examined relationships between hospital admission time and disabilities at discharge while considering case severity.
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Long-term prognosis of patients with hepatitis B infection: causes of death and utility of nucleos(t)ide analogue therapy.
J. Gastroenterol.
PUBLISHED: 09-17-2014
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Long-term nucleos(t)ide analogue (NA) therapy for chronic hepatitis B (CHB) patients has been reported to reduce the risk of hepatocellular carcinoma (HCC) development. However, survival rates and causes of death in CHB patients either treated or not treated with NA therapy are unclear. Therefore, we investigated the prognosis of CHB in both of these groups.
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Impact of hepatitis B virus integration into liver tissue on the efficacy of peginterferon and ribavirin therapy in hepatitis B virus-negative chronic hepatitis C patients.
J. Clin. Gastroenterol.
PUBLISHED: 09-10-2014
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Integration of hepatitis B virus (HBV) DNA into host hepatic DNA is found in patients without HBV surface antigen (HBsAg). We investigated the prevalence of HBV integration and its association with the outcome of peginterferon (PEG-IFN) and ribavirin combination therapy in HBsAg-negative chronic hepatitis C patients.
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Biochemical staging of the chronic hepatic lesions of Wilson disease.
Nagoya J Med Sci
PUBLISHED: 08-19-2014
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Copper toxicity steadily affects the livers of patients with Wilson disease. However, the toxic effect of copper on serum aspartate and alanine aminotransferase levels remains to be clarified as a prerequisite for diagnostic tests. The clinical records of 33 cases were analyzed to clarify the natural history of Wilson disease. Phenotypes were simplified into hepatic, acute, and neurologic. The bio-low stage of both enzymes was less than 40 IU/L, the bio-moderate stage was intermediate between 40 and 200 IU/L, and the bio-high stage was more than 200 IU/L of either or both enzymes. Rebounded enzyme levels at the recovery period from anemia were presumed to be the chronic baselines when pre-anemic enzyme levels were not available in the acute phenotype. We investigated whether these enzyme levels may provide information useful for screening patients. The natural history of chronic Wilson disease consisted of the first increasing and second decreasing phases. The clinical courses of a 4-year-old boy and 12-year-old girl were representative of the 2 phases, respectively. All but one patient were in the decreasing phase. Negative correlations were obtained between age and enzyme level in the decreasing phase. The hepatic phenotype may be a prototype found throughout the 2 phases, and acute and neurologic phenotypes may be major complications in the bio-moderate and bio-low stages of the decreasing phase, respectively. Biochemical staging may provide a better understanding of Wilson disease when combined with phenotypes. Bio-high stage patients should be referred to a medical center for diagnosis.
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Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials.
Lancet
PUBLISHED: 08-05-2014
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Alteplase is effective for treatment of acute ischaemic stroke but debate continues about its use after longer times since stroke onset, in older patients, and among patients who have had the least or most severe strokes. We assessed the role of these factors in affecting good stroke outcome in patients given alteplase.
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Stroke and cerebrovascular diseases in patients with chronic kidney disease.
Lancet Neurol
PUBLISHED: 07-18-2014
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Chronic kidney disease, defined as a reduced glomerular filtration rate or increased urinary albumin excretion, is recognised as a rapidly growing global health burden, and increasing evidence suggests that it contributes to the risk and severity of cerebrovascular diseases. In particular, chronic kidney disease is an established risk factor for stroke and is also strongly associated with subclinical cerebrovascular abnormalities and cognitive impairment, partly because it shares several traditional and non-traditional risk factors, and sometimes uraemia-related and dialysis-related factors, with cerebrovascular diseases. The effect of chronic kidney disease on incident stroke differs among regions and races and is greater in Asian than in non-Asian people. Chronic kidney disease seems to be predictive of severe neurological deficits and poor vital and functional outcomes after both ischaemic and haemorrhagic strokes, which is partly due to the limitations of pharmacotherapies, including limited use and effects of novel oral anticoagulants, other antithrombotic treatments, and reperfusion treatment for hyperacute ischaemic stroke. In view of the strong two-way association between stroke and kidney disease, the pathophysiological interactions between the brain and kidney should be the subject of intensive study.
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Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open-label, phase 3 trial.
J. Viral Hepat.
PUBLISHED: 06-27-2014
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Genotype 2 hepatitis C virus (HCV) accounts for up to 30% of chronic HCV infections in Japan. The standard of care for patients with genotype 2 HCV - peginterferon and ribavirin for 24 weeks - is poorly tolerated, especially among older patients and those with advanced liver disease. We conducted a phase 3, open-label study to assess the efficacy and safety of an all-oral combination of the NS5B polymerase inhibitor sofosbuvir and ribavirin in patients with chronic genotype 2 HCV infection in Japan. We enrolled 90 treatment-naïve and 63 previously treated patients at 20 sites in Japan. All patients received sofosbuvir 400 mg plus ribavirin (weight-based dosing) for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after therapy (SVR12). Of the 153 patients enrolled and treated, 60% had HCV genotype 2a, 11% had cirrhosis, and 22% were over the aged 65 or older. Overall, 148 patients (97%) achieved SVR12. Of the 90 treatment-naïve patients, 88 (98%) achieved SVR12, and of the 63 previously treated patients, 60 (95%) achieved SVR12. The rate of SVR12 was 94% in patients with cirrhosis and in those aged 65 and older. No patients discontinued study treatment due to adverse events. The most common adverse events were nasopharyngitis, anaemia and headache. Twelve weeks of sofosbuvir and ribavirin resulted in high rates of SVR12 in treatment-naïve and previously treated patients with chronic genotype 2 HCV infection. The treatment was safe and well tolerated by patients, including the elderly and those with cirrhosis.
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Blood pressure variability on antihypertensive therapy in acute intracerebral hemorrhage: the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-intracerebral hemorrhage study.
Stroke
PUBLISHED: 06-26-2014
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The associations between early blood pressure (BP) variability and clinical outcomes in patients with intracerebral hemorrhage after antihypertensive therapy, recently clarified by a post hoc analysis of Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2), were confirmed using the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-intracerebral hemorrhage study cohort.
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Effect of Peginterferon alfa-2b and Ribavirin on Hepatocellular Carcinoma Prevention in Older Patients with Chronic Hepatitis C.
J. Gastroenterol. Hepatol.
PUBLISHED: 06-23-2014
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The population of patients chronically infected with hepatitis C virus (HCV) is aging and the number of older patients with HCV-related hepatocellular carcinoma (HCC) is increasing. The purpose of this study was to elucidate the effects of peginterferon and ribavirin combination therapy on prevention of HCC in older patients with chronic hepatitis C (CH-C).
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Intravenous Nicardipine Dosing for Blood Pressure Lowering in Acute Intracerebral Hemorrhage: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-Intracerebral Hemorrhage Study.
J Stroke Cerebrovasc Dis
PUBLISHED: 06-20-2014
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Intravenous nicardipine is commonly used to reduce elevated blood pressure in acute intracerebral hemorrhage (ICH). We determined factors associated with nicardipine dosing and the association of dose with clinical outcomes in hyperacute ICH.
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Association of interleukin 28B polymorphism and mutations in the NS5A region of hepatitis C virus genotype 2 with interferon responsiveness.
J. Gastroenterol. Hepatol.
PUBLISHED: 06-15-2014
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Background & Aims: The single nucleotide polymorphism (SNP) of interleukin 28B (IL28B) and the mutations in the NS5A region of hepatitis C virus (HCV) genotype 1 have been associated with response to interferon (IFN) therapy. However, these relationships in patients with HCV genotype 2 are not well understood. The aim of this study was to investigate whether the SNP of IL28B (rs8099917) and amino acid substitutions in the NS5A region in patients with HCV genotype 2 affect the response to IFN and ribavirin combination therapy. Methods: The study enrolled 286 patients with chronic hepatitis C genotype 2. Patients received pegylated-IFN-alpha 2b once each week plus oral ribavirin daily for 24 weeks. Results: Of the 286 patients, 215 (75.2%) achieved sustained virologic response (SVR). Rate of SVR was similar in patients with IL28B TT allele (76%) and those with TG or GG alleles (72%). Patients with SVR were younger than those without SVR (p<0.001). SVR was achieved in 65.9% of patients with wild-type IFN sensitivity-determining region (ISDR) and 83.5% of patients with mutant-type (p<0.001). There were no significant differences in other factors, including sex, alanine aminotransferase, platelet count, HCV viral load, HCV genotype, and IL28B genotype. The factors related to SVR on multivariate analysis were age (p=0.019) and ISDR (p=0.003). Conclusions: ISDR sequence variations are significantly associated with IFN responsiveness in patients with HCV genotype 2. The SNP of IL28B was not associated with SVR in patients with HCV genotype 2.
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Factors associated with unfavorable outcome in minor ischemic stroke.
Neurology
PUBLISHED: 06-06-2014
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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.
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Cross-sectional survey of workload and burnout among Japanese physicians working in stroke care: the nationwide survey of acute stroke care capacity for proper designation of comprehensive stroke center in Japan (J-ASPECT) study.
Circ Cardiovasc Qual Outcomes
PUBLISHED: 05-13-2014
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Burnout is common among physicians and affects the quality of care. We aimed to determine the prevalence of burnout among Japanese physicians working in stroke care and evaluate personal and professional characteristics associated with burnout.
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[Case of small bowel angioectasia in which the resection site was angiographically detected using intraoperative dye infusion].
Nihon Shokakibyo Gakkai Zasshi
PUBLISHED: 04-29-2014
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A 37-year-old Japanese man undergoing treatment for dilated cardiomyopathy was presented with weakness and melena. He had conjunctival pallor and difficulty in standing;his blood pressure was 81/62 mmHg. Abdominal computed tomography revealed contrast dye leakage into the small intestine. He was diagnosed with hemorrhagic shock secondary to intestinal bleeding;we administered large volumes of intravenous fluid along with performing a blood transfusion. We then performed angiography to determine the site of bleeding angioectasia and placed a catheter into the affected artery. We identified the resection site using an intraoperative dye infusion via the catheter, and successfully performed small bowel resection. He was subsequently discharged without complications.
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Mutation of Spry2 Induces Proliferation and Differentiation of Osteoblasts but Inhibits Proliferation of Gingival Epithelial Cells.
J. Cell. Biochem.
PUBLISHED: 04-08-2014
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Sprouty was identified as an inhibitor of the fibroblast growth factor (FGF) receptor, and Sprouty2 (Spry2) functions as a negative regulator of receptor tyrosine kinase signaling. In this study, we investigated how inhibition of Spry2 affects osteoblasts and gingival epithelial cells in periodontal tissue regeneration in vitro. Transduction of a dominant-negative mutant of Spry2 (Y55A-Spry2) enhanced basic fibroblast growth factor (bFGF)- and epidermal growth factor (EGF)-induced ERK activation in MC3T3-E1 osteoblastic cells. In contrast, it decreased their activation in GE1 cells. Consistent with these observations, Y55A-Spry2 increased osteoblast proliferation with bFGF and EGF stimulation, whereas the proliferation of Y55A-Spry2-introduced GE1 cells was decreased via the ubiquitination and degradation of EGF receptors (EGFRs). In addition, Y55A-Spry2 caused upregulation of Runx2 expression and downregulation of Twist, a negative regulator of Runx2, with treatment of bFGF and EGF, resulting in enhanced osteoblastogenesis accompanied by alkaline phosphatase activation and osteocalcin expression in MC3T3-E1 cells. These data suggest that suppression of Spry2 expression induces proliferation and differentiation of osteoblastic cells after the addition of a bFGF and EGF cocktail but inhibits proliferation in gingival epithelial cells. These in vitro experiments may provide a molecular basis for novel therapeutic approaches in periodontal tissue regeneration. Taken together, our study proposes that combined application of an inhibitor for tyrosine 55 of Spry2, bFGF, and EGF may effectively allow alveolar bone growth and block the ingrowth of gingival epithelial cells toward bony defects, biologically mimicking a barrier effect in guided tissue regeneration, with in vivo investigation in the future. This article is protected by copyright. All rights reserved.
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Characteristics and outcomes of HCV genotype-1-infected patients treated with peginterferon and ribavirin combination therapy with discordant HCV responses 4 and 12 weeks after starting therapy.
Intervirology
PUBLISHED: 04-08-2014
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Some patients with chronic hepatitis C virus (HCV) infection fail to achieve complete early virologic response (EVR) despite a marked decrease in HCV RNA at 4 weeks. We investigated the characteristics and final treatment outcomes of this patient subpopulation.
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Factors contributing to mortality and morbidity in pregnancy-associated intracerebral hemorrhage in Japan.
J. Obstet. Gynaecol. Res.
PUBLISHED: 04-02-2014
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The aim of this study was to analyze the causes and outcomes for intracerebral hemorrhage (ICH) occurring during pregnancy and postnatally.
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Aortic transgraft hemorrhage after intravenous tissue plasminogen activator therapy in patients with acute ischemic stroke.
J Stroke Cerebrovasc Dis
PUBLISHED: 03-18-2014
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The safety of intravenous recombinant tissue plasminogen activator (IV tPA) therapy for patients with an aortic aneurysm or undergoing aortic graft replacement has not been established. We evaluated the incidence, bleeding site, coagulation factors, and clinical outcomes of patients treated with IV tPA for acute stroke.
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Factors associated with sustained virological response in 24-week telaprevir-based triple therapy for chronic hepatitis C genotype 1b patients with the IL28B minor genotype.
Hepatol. Res.
PUBLISHED: 03-11-2014
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Single nucleotide polymorphisms (SNP) near the interleukin-28B (IL28B) gene affect the outcome of 24-week telaprevir-based triple therapy with telaprevir, pegylated interferon-? and ribavirin for chronic hepatitis C virus (HCV) genotype 1b patients. We aimed to identify factors associated with treatment outcomes in patients with the unfavorable minor IL28B SNP genotype, who have poor response to combination therapy.
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Effects of stroke education using an animated cartoon and a manga on elementary school children.
J Stroke Cerebrovasc Dis
PUBLISHED: 02-12-2014
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Stroke education for the youth is expected to reduce prehospital delay by informing the bystander of appropriate action to take and providing knowledge to prevent onset of stroke in future. Previously, we developed effective teaching materials consisting of an animated cartoon and a Manga for junior high school students. The aim of this study was to evaluate the feasibility and effectiveness of our educational materials for stroke education taught by schoolteachers to elementary school children.
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Predictors of response to 24-week telaprevir-based triple therapy for treatment-naïve genotype 1b chronic hepatitis C patients.
Gastroenterol Res Pract
PUBLISHED: 02-07-2014
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We evaluated the genetic variation in rs8099917, substitutions in core amino acid (aa) 70, and the number of aa substitutions in the interferon sensitivity-determining region (ISDR) on the prediction of sustained virological response (SVR) in treatment-naïve hepatitis C virus (HCV) genotype 1b (G1b) patients. This multicenter study involved 150 Asian treatment-naïve patients infected with HCV G1b who received 12 weeks of telaprevir in combination with 24 weeks of peginterferon-?-2b and ribavirin. The baseline and treatment-related factors potentially associated with SVR were determined by multivariate logistic regression analysis. Virological response was analyzed on an intent-to-treat basis. Cessation of the therapy due to adverse effects occurred in only 2 patients, who discontinued the trial at 10 weeks and at 2 weeks due to cerebral infarction and renal impairment, respectively. Among the 150 patients in whom the final virological response was determined, only genotype TT in rs8099917 was identified as a pretreatment predictor (P = 7.38 × 10(-4)). Achievement of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 of treatment, was identified as an after-starting-treatment predictor (P = 2.47 × 10(-5)). However, neither a substitution in core aa 70 nor the number of substitutions in the ISDR affected treatment outcome.
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Diagnostic accuracy for macroscopic classification of nodular hepatocellular carcinoma: comparison of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and angiography-assisted computed tomography.
J. Gastroenterol.
PUBLISHED: 02-07-2014
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The macroscopic type of hepatocellular carcinoma (HCC) is a predictor of prognosis. We clarified the diagnostic value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in the macroscopic classification of nodular hepatocellular carcinoma (HCC) as compared to angiography-assisted computed tomography (CT).
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THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6?mg/kg (THAWS) Trial.
Int J Stroke
PUBLISHED: 02-06-2014
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Because of lack of information regarding timing of stroke, patients who suffer stroke during sleep are generally ineligible for intravenous thrombolysis, although many of these patients could potentially recover with this treatment. Magnetic resonance image findings with positive diffusion-weighted imaging and no marked parenchymal hyperintensity on fluid-attenuated inversion recovery (negative pattern) can identify acute ischemic stroke patients within 4·5?h from symptom onset.
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Utility of contrast-enhanced ultrasound with perflubutane for diagnosing the macroscopic type of small nodular hepatocellular carcinomas.
Eur Radiol
PUBLISHED: 02-04-2014
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To clarify the diagnostic value of contrast-enhanced ultrasound (CEUS) with perflubutane in the macroscopic classification of small nodular hepatocellular carcinomas (HCCs).
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Three-dimensional analysis of the left atrial appendage for detecting paroxysmal atrial fibrillation in acute ischemic stroke.
Int J Stroke
PUBLISHED: 02-02-2014
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Atrial fibrillation impairs left atrial appendage function and the thrombus formation in the left atrial appendage is a major cause of cardioembolic stroke.
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A 48-week telaprevir-based triple combination therapy improves sustained virological response rate in previous non-responders to peginterferon and ribavirin with genotype 1b chronic hepatitis C: A multicenter study.
Hepatol. Res.
PUBLISHED: 02-02-2014
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The sustained virological response (SVR) rate of non-responders to peginterferon and ribavirin therapy (PR) is low for 24-week telaprevir-based triple combination therapy (T12PR24), compared to that of treatment-naïve patients or previous-treatment relapsers. This study investigated which characteristics of non-responders were associated with a better SVR rate to 48-week therapy (T12PR48).
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Heat shock protein 20 (HSPB6) regulates apoptosis in human hepatocellular carcinoma cells: Direct association with Bax.
Oncol. Rep.
PUBLISHED: 01-28-2014
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A small heat shock protein (HSP), HSP20 (HSPB6) is ubiquitously expressed in various tissues and has several functions. We previously reported that the expression of HSP20 protein in human hepatocellular carcinoma (HCC) cells is inversely proportional to the progression of HCC. In addition, we showed that HSP20 is associated with phosphoinositide 3-kinase (PI3K) and inhibits the proliferation of HCC cells via suppression of the AKT signaling pathway. However, the relationship between HSP20 and apoptosis in HCC has not yet been elucidated. To clarify whether HSP20 is implicated in the apoptosis of HCC cells, in the present study, we examined the effect of HSP20 on caspases, the central regulators of apoptosis, using human HCC-derived HuH7 cells that are transfected with wild-type human HSP20 (HSP20-overexpressing cells). The cleavage of caspase-3 and caspase-7 in HSP20-overexpressing cells was enhanced compared with the empty vector-transfected cells (control cells). In addition, the cleavage of nuclear poly (ADP-ribose) polymerase (PARP) in HSP20-overexpressing cells was also strengthened. We further investigated the direct targets of HSP20 focusing on Bcl-2 family proteins in the HSP20-overexpressing cells. HSP20 proteins in the cells were coimmunoprecipitated with Bax. On the contrary, Bad, Bcl-2 and Bcl-xL were not coimmunoprecipitated with HSP20. These findings strongly suggest that HSP20 directly associates with Bax and stimulates caspase cascade in human HCC cells.
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Changes in highly sensitive alpha-fetoprotein for the prediction of the outcome in patients with hepatocellular carcinoma after hepatectomy.
Cancer Med
PUBLISHED: 01-20-2014
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We investigated changes in highly sensitive lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (hsAFP-L3) measured using a novel method and its predictive ability for prognosis in patients with hepatocellular carcinoma (HCC) who underwent curative hepatectomy, comparing to other HCC tumor markers, that is, AFP, des-gamma-carboxy prothrombin (DCP), and AFP-L3 measured with conventional method (cAFP-L3). AFP, DCP, and AFP-L3 including both cAFP-L3 and hsAFP-L3 were measured before and after curative hepatectomy in 187 patients. The percentage of patients with elevated tumor marker levels pre- and postoperatively was compared, and recurrence-free and overall survival rates were analyzed based on changes in tumor markers. The percentages of patients with elevated AFP, DCP, and cAFP-L3 decreased postoperatively. In contrast, the percentage of patients with elevated hsAFP-L3 did not decrease postoperatively. Both recurrence-free and overall survival rates were significantly lower in patients whose tumor marker levels remained elevated postoperatively than patients without tumor marker elevation postoperatively. Recurrence-free and overall survival rates of patients in whom hsAFP-L3 became elevated postoperatively despite normal preoperative hsAFP-L3 levels were significantly lower than those of patients with normal hsAFP-L3 postoperatively, and were similar to those of patients with persistent elevation. Preoperative elevations of AFP, DCP, and cAFP normalized in many patients postoperatively, but not for hsAFP-L3. The elevation of hsAFP-L3 identifies patients with poor prognosis despite the normalization of AFP and DCP.
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Continuous antihypertensive therapy throughout the initial 24 hours of intracerebral hemorrhage: the stroke acute management with urgent risk-factor assessment and improvement-intracerebral hemorrhage study.
Stroke
PUBLISHED: 01-14-2014
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A short duration (<24 hours) of antihypertensive therapy (AHT) after acute intracerebral hemorrhage (ICH) may be sufficient because active bleeding generally ceases within several hours. We aimed to determine the association between sequential systolic blood pressure (SBP) levels during AHT and outcomes in ICH patients.
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Etiological mechanisms of isolated pontine infarcts based on arterial territory involvement.
J. Neurol. Sci.
PUBLISHED: 01-09-2014
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Pontine infarcts can be classified into four regions based on the vascular anatomy: anteromedial, anterolateral, lateral and posterior. The purpose of this study was to determine if different etiological mechanisms are responsible for these four types of pontine infarcts.
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Early-onset dystonia after supplementary motor area infarction.
J Stroke Cerebrovasc Dis
PUBLISHED: 01-07-2014
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A 63-year-old patient with the right supplementary motor area infarct developed early-onset dystonia in the left upper extremity. The mechanisms involved in the genesis of focal dystonia are discussed with emphasis on cortical basal ganglia circuit and efferent projections from the supplementary motor area.
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Stroke education using an animated cartoon and a manga for junior high school students.
J Stroke Cerebrovasc Dis
PUBLISHED: 01-06-2014
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We investigated whether junior high school students could be educated regarding stroke with an animated cartoon and a Manga that we produced for the purpose of dissemination of this knowledge.
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The effectiveness of a stroke educational activity performed by a schoolteacher for junior high school students.
J Stroke Cerebrovasc Dis
PUBLISHED: 01-03-2014
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The purpose of this study was to determine whether our stroke education system can help junior high school students acquire stroke knowledge when performed by a schoolteacher.
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Comparison of hepatocellular carcinoma miRNA expression profiling as evaluated by next generation sequencing and microarray.
PLoS ONE
PUBLISHED: 01-01-2014
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MicroRNA (miRNA) expression profiling has proven useful in diagnosing and understanding the development and progression of several diseases. Microarray is the standard method for analyzing miRNA expression profiles; however, it has several disadvantages, including its limited detection of miRNAs. In recent years, advances in genome sequencing have led to the development of next-generation sequencing (NGS) technologies, which significantly advance genome sequencing speed and discovery. In this study, we compared the expression profiles obtained by next generation sequencing (NGS) with the profiles created using microarray to assess if NGS could produce a more accurate and complete miRNA profile. Total RNA from 14 hepatocellular carcinoma tumors (HCC) and 6 matched non-tumor control tissues were sequenced with Illumina MiSeq 50-bp single-end reads. Micro RNA expression profiles were estimated using miRDeep2 software. As a comparison, miRNA expression profiles for 11 out of 14 HCCs were also established by microarray (Agilent human microRNA microarray). The average total sequencing exceeded 2.2 million reads per sample and of those reads, approximately 57% mapped to the human genome. The average correlation for miRNA expression between microarray and NGS and subtraction were 0.613 and 0.587, respectively, while miRNA expression between technical replicates was 0.976. The diagnostic accuracy of HCC, p-value, and AUC were 90.0%, 7.22×10(-4), and 0.92, respectively. In summary, NGS created an miRNA expression profile that was reproducible and comparable to that produced by microarray. Moreover, NGS discovered novel miRNAs that were otherwise undetectable by microarray. We believe that miRNA expression profiling by NGS can be a useful diagnostic tool applicable to multiple fields of medicine.
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Effects of comprehensive stroke care capabilities on in-hospital mortality of patients with ischemic and hemorrhagic stroke: J-ASPECT study.
PLoS ONE
PUBLISHED: 01-01-2014
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The effectiveness of comprehensive stroke center (CSC) capabilities on stroke mortality remains uncertain. We performed a nationwide study to examine whether CSC capabilities influenced in-hospital mortality of patients with ischemic and hemorrhagic stroke.
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Contribution of neurologists to emergent stroke medicine in Japan.
Rinsho Shinkeigaku
PUBLISHED: 12-03-2013
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Although the demand for emergent stroke management has been increasing, stroke specialists are undersupplied in Japan. Neurosurgeons, not neurologists, often perform acute stroke care. Since medical management is the mainstream of stroke care, neurologists should be fully aware of their role as a commander of the stroke care unit. Neurologists have to confront wide-ranging areas of neurological diseases including neurological emergency and intractable chronic diseases, and such diversity should be respected. Nevertheless, neurological departments in the medical schools and hospitals over Japan should constantly train a certain number of stroke specialists to meet the demands of patients, since stroke is the largest neurological disease in Japan.
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Endovascular Treatment of Acute Stroke with Major Vessel Occlusion before Approval of Mechanical Thrombectomy Devices in Japan: Japanese Registry of Neuroendovascular Therapy (JR-NET) and JR-NET 2.
Neurol. Med. Chir. (Tokyo)
PUBLISHED: 11-29-2013
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The aim of this study was to clarify the general status and historical transition of endovascular therapy (EVT) of acute stroke with major vessel occlusion before approval of mechanical thrombectomy devices in Japan from January 2005 to December 2009. We extracted 1,409 acute ischemic stroke patients receiving EVT (513 women, 69.8 ± 11.8 years) from two nationwide registry studies, the Japanese Registry of Neuroendovascular Therapy (JR-NET) and JR-NET 2. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 18, and 81.3% of the patients received EVT within 6 hours after symptom onset. The culprit occluded arteries were the internal carotid artery (ICA) in 21.2%, middle cerebral artery (MCA) in 53.0%, and basilar artery (BA) in 20.6%. Intravenous thrombolysis was administered to 6.7% of the patients, and EVT mainly consisted of intra-arterial thrombolysis and percutaneous balloon angioplasty/balloon clot disruption. The final recanalization rate was 82.5%, and the clinical outcome was favorable in 35.8% and fatal in 11.6% at 30 days after onset or at discharge. There was no significant change in neurological severity at baseline throughout the study period, but the onset-to-treatment time became longer and the proportion of ICA or BA occlusion increased annually. Although the final recanalization rate was similar throughout the study period, the incidence of a favorable outcome tended to decreased annually from 41.0% to 29.0%. These results could be considered as baseline data that can be used to validate the beneficial effects of novel EVT devices in Japan.
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Baseline factors and very early viral response (week 1) for predicting sustained virological response in telaprevir-based triple combination therapy for Japanese genotype 1b chronic hepatitis C patients: a multicenter study.
J. Gastroenterol.
PUBLISHED: 10-12-2013
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Genetic polymorphisms near Interleukin 28B (IL28B) (rs8099917) and a rapid virological response (RVR) have been reported as predictors for a sustained virological response (SVR) to telaprevir (TVR)-based triple combination therapy. However, the association between SVR and viral kinetics earlier than week 4 after initiation of therapy remains unclear. Thus, we evaluated the SVR prediction ability of baseline factors and reduced hepatitis C virus (HCV) RNA levels at week 1 after the initiation of TVR-based therapy in Japanese genotype-1b chronic hepatitis C (CHC) patients.
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Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy without Anterior Temporal Pole Involvement: A Case Report.
J Stroke Cerebrovasc Dis
PUBLISHED: 10-01-2013
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The location of white matter lesions, especially in the anterior temporal poles (ATP), is helpful in the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We report a 49-year-old man with CADASIL who developed migraine with atypical aura, silent lacunar infarcts, and leukoencephalopathy without involvement of the ATP. The prevalence of migraine with aura in subjects with CADASIL is several times greater than that in the general population. Particularly in patients with CADASIL, the aura is often atypical (hemiplegic, basilar, or prolonged). A diagnosis of CADASIL should be considered in patients with lacunar infarcts, leukoencephalopathy, and migraine with atypical aura, even in the absence of white matter lesion in the ATPs.
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Impact of chronic kidney disease on carotid atherosclerosis according to blood pressure category: the suita study.
Stroke
PUBLISHED: 10-01-2013
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We aimed to clarify the association of chronic kidney disease (CKD) with carotid atherosclerosis and the impact of CKD on carotid atherosclerosis according to blood pressure categories in an urban general population.
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Antithrombotic therapy for pregnant women.
Neurol. Med. Chir. (Tokyo)
PUBLISHED: 08-28-2013
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Coagulability increases during pregnancy, and thromboembolism can easily occur. Venous thromboembolism is a cause of death in pregnant women, but arterial thrombosis such as ischemic stroke in pregnancy is also not uncommon. In pharmacotherapy for thromboembolism in pregnant women, fetal toxicity and teratogenicity must be carefully considered. As anticoagulants in pregnant women, unfractionated heparin and low-molecular-weight heparin are recommended, but warfarin is not recommended since it has a low molecular weight and crosses the placenta. Various types of new oral anticoagulant drugs have been available in Japan since 2011. However, the Japanese package inserts for these anticoagulants advise quite cautious administration in pregnant women. The guidelines on pregnant women include less information about antiplatelet drugs than anticoagulant drugs. Aspirin may cause teratogenicity and fetal toxicity, and perinatal mortality is increased. However, when low doses of aspirin are administered as antiplatelet therapy, the US Food and Drug Administration has assigned pregnancy category C, and treatment is relatively safe. Neurosurgeons and neurologists commonly encounter pregnant women with thromboembolism, such as ischemic stroke. Up-to-date information and correct selection of drugs are necessary in consultation with specialists in perinatal care.
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Stroke Education Program of Act FAST for Junior High School Students and Their Parents.
J Stroke Cerebrovasc Dis
PUBLISHED: 08-13-2013
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We produced a stroke education program using the FAST (facial droop, arm weakness, speech disturbance, time to call an ambulance) mnemonic.
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Features of Patients with Transient Monocular Blindness: A Multicenter Retrospective Study in Japan.
J Stroke Cerebrovasc Dis
PUBLISHED: 08-02-2013
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Transient monocular blindness (TMB) is associated with a transient ischemic attack (TIA). The purpose of this study was to investigate the features of TMB in the Japanese population using data from a multicenter retrospective study of TIA.
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Characteristics of elderly hepatitis C virus-associated hepatocellular carcinoma patients.
J. Gastroenterol. Hepatol.
PUBLISHED: 07-28-2013
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The average age of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) patients has been rising in Japan. We evaluate characteristics of HCV-positive patients who develop HCC in older age to determine an optimal surveillance strategy.
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Neurologic Improvement without Angiographic Improvement after Antithyroid Therapy in a Patient with Moyamoya Syndrome.
J Stroke Cerebrovasc Dis
PUBLISHED: 07-25-2013
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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.
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Effects of intensive and moderate public education on knowledge of early stroke symptoms among a Japanese population: the Acquisition of Stroke Knowledge study.
Stroke
PUBLISHED: 07-25-2013
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To assess the effects of intensive and moderate public education on knowledge of early stroke symptoms among a general Japanese population.
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[Current and future aspects of intravenous thrombolysis for acute stroke].
Brain Nerve
PUBLISHED: 07-09-2013
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Intravenous thrombolysis using alteplase was approved for clinical use for acute ischemic stroke treatment in Japan in 2005, on the basis of the results of a domestic clinical trial, Japan Alteplase Clinical Trial. This therapeutic strategy has become the standard strategy during the following 8 years. However, this therapy still has room for improvement. One of the important drawbacks of intravenous thrombolysis is the limited therapeutic time window. On the basis of the results of the European Cooperative Acute Stroke Study III and the pooled analysis, the current time window is within 4.5 h of stroke onset. The window may be extended to 6 h or longer, probably by appropriate determination of the eligibility of a patient for receiving therapy by using penumbral imaging techniques, such as diffusion-weighted imaging (DWI)/perfusion-weighted imaging mismatch and DWI/magnetic resonance imaging mismatch. Newer-generation recombinant tissue-type plasminogen activators, such as desmoteplase and tenecteplase, will also help extend the time window. Patients with wake-up and unclear-onset strokes are generally ineligible for thrombolysis; therefore, the optimal therapeutic strategy for such patients should be established. Another important drawback is acute stroke therapy paralleling or following intravenous thrombolysis. Mechanical recanalization by endovascular therapy, antithrombotic therapy, neuroprotective therapy (e.g., using intravenous free radical scavenger), and sonothrombolysis are promising candidates for combined use with intravenous thrombolysis.
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Oscillating thrombi in bilateral extracranial internal carotid arteries demonstrated on ultrasonography: two autopsy cases of cardioembolic stroke.
Intern. Med.
PUBLISHED: 06-04-2013
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We herein report two autopsy cases of severe cardioembolic stroke with oscillating thrombi in the bilateral extracranial internal carotid arteries (ICAs) demonstrated on carotid ultrasonography performed on admission. An autopsy study of case 1 conducted on the third hospital day revealed no thrombi, while that of case 2 conducted on the 42nd hospital day revealed red thrombi in the extracranial ICAs. Our postmortem studies confirm that oscillating thrombi may be seen in the region of blood stasis caused by occlusion of the distal portion of the ICA, thus reflecting a pre-state of thrombus formation.
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High-sensitivity Lens culinaris agglutinin-reactive alpha-fetoprotein assay predicts early detection of hepatocellular carcinoma.
J. Gastroenterol.
PUBLISHED: 05-19-2013
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Prognosis of patients with hepatocellular carcinoma (HCC) remains poor because HCC is frequently diagnosed late. Therefore, regular surveillance has been recommended to detect HCC at the early stage when curative treatments can be applied. HCC biomarkers, including Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), are widely used for surveillance in Japan. A newly developed immunoassay system measures AFP-L3 % with high sensitivity. This retrospective study aimed to evaluate clinical utility of high-sensitivity AFP-L3 (hs-AFP-L3) as a predictor of early stage HCC in surveillance at a single site.
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The Impact of Comprehensive Stroke Care Capacity on the Hospital Volume of Stroke Interventions: A Nationwide Study in Japan: J-ASPECT Study.
J Stroke Cerebrovasc Dis
PUBLISHED: 05-16-2013
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The association between comprehensive stroke care capacity and hospital volume of stroke interventions remains uncertain. We performed a nationwide survey in Japan to examine the impact of comprehensive stroke care capacity on the hospital volume of stroke interventions.
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Factors Associated with Proximal Carotid Axis Occlusion in Patients with Acute Stroke and Atrial Fibrillation.
J Stroke Cerebrovasc Dis
PUBLISHED: 05-14-2013
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Patients with atrial fibrillation (AF) are more likely to exhibit proximal carotid axis occlusion than those without AF. However, clinical characteristics associated with proximal arterial occlusion (PAO) in acute stroke patients with AF are not fully known. This study was aimed to elucidate the factors correlated with PAO.
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Low serum calcium levels contribute to larger hematoma volume in acute intracerebral hemorrhage.
Stroke
PUBLISHED: 05-14-2013
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We investigate whether admission serum calcium levels are associated with hematoma volume, stroke severity, and outcomes in patients with acute intracerebral hemorrhage.
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CHADS2 and CHA2DS2-VASc scores as bleeding risk indices for patients with atrial fibrillation: the Bleeding with Antithrombotic Therapy Study.
Hypertens. Res.
PUBLISHED: 05-08-2013
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The CHADS2 and CHA2DS2-VASc scores, that is, ischemic stroke risk indices for patients having atrial fibrillation (AF), may also be useful as bleeding risk indices. Japanese patients with AF, who routinely took oral antithrombotic agents were enrolled from a prospective, multicenter study. The CHADS2 and CHA2DS2-VASc scores were assessed based on information at entry. Scores of 0, 1 and ?2 were defined as the low, intermediate and high ischemic risk categories, respectively, for each index. Of 1221 patients, 873 took warfarin, 114 took antiplatelet agents and 234 took both. The annual incidence of ischemic stroke was 0.76% in the low-risk category, 1.46% in the intermediate-risk category and 2.90% in the high-risk category by CHADS2 scores, and 1.44, 0.42 and 2.50%, respectively, by CHA2DS2-VASc scores. The annual incidence of major bleeding in each category was 1.52, 2.19 and 2.25% by CHADS2, and 1.44, 1.69 and 2.24% by CHA2DS2-VASc. After multivariate adjustment, the CHADS2 was associated with ischemia (odds ratio 1.76, 95% confidence interval 1.03-3.38 per 1-category increase) and the CHA2DS2-VASc tended to be associated with ischemia (2.18, 0.89-8.43). On the other hand, associations of the indices with bleeding were weak. In conclusion, bleeding risk increased gradually as the CHADS2 and CHA2DS2-VASc scores increased in Japanese antithrombotic users, although the statistical impact was rather weak compared with their predictive power for ischemic stroke.Hypertension Research advance online publication, 7 November 2013; doi:10.1038/hr.2013.150.
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Intra- and extracranial atherosclerotic disease in acute spontaneous intracerebral hemorrhage.
J. Neurol. Sci.
PUBLISHED: 05-07-2013
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There is little information about intracranial atherosclerotic disease (ICAD) and extracranial atherosclerotic disease (ECAD) in patients with acute spontaneous intracerebral hemorrhage (ICH). The purpose of the present study was to elucidate the prevalence of and the factors that correlate with ICAD and ECAD in patients with ICH.
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Clinical significance of fluid-attenuated inversion recovery vascular hyperintensities in transient ischemic attack.
Stroke
PUBLISHED: 05-07-2013
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Fluid-attenuated inversion recovery vascular hyperintensity (FVH) is often identified in patients with acute ischemic stroke. The purpose of this study was to determine the clinical significance of FVH in patients with transient ischemic attack (TIA).
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Comparison of the European and Japanese guidelines for the acute management of intracerebral hemorrhage.
Cerebrovasc. Dis.
PUBLISHED: 05-06-2013
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Different aspects of acute stroke management and strategies for stroke prevention derive from two viewpoints: specific traditional and historical backgrounds and evidence-based medicine from modern randomized controlled trials (RCTs), meta-analysis and authorized clinical practice guidelines (GLs). Regarding intracerebral hemorrhage (ICH), Cerebrovascular Diseases published the 2006 European stroke initiative recommendations for the management of ICH. In 2009, the revised Japanese GLs for the management of stroke, including that of ICH, appeared in Japanese. Whereas GLs for the prevention and treatment of ischemic stroke were presented in detail, recommendations with regard to ICH are relatively rare both in Japan and Europe.
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Comparison of the European and Japanese guidelines for the management of ischemic stroke.
Cerebrovasc. Dis.
PUBLISHED: 05-06-2013
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Different aspects of acute stroke management and strategies for stroke prevention derive from two viewpoints: specific traditional and historical backgrounds and evidence-based medicine from modern randomized controlled trials (RCTs), meta-analysis and authorized clinical practice guidelines (GLs). Regarding stroke, GLs have been published by national and international organizations in different languages, most frequently in English. Cerebrovascular Diseases published the European GLs for the management of ischemic stroke and transient ischemic attacks in 2003, with an update in 2008. At about the same time (in 2004), the first Japanese GLs for the management of stroke appeared in Japanese. The first English version of the updated Japanese GLs was published only in 2011 and included differently approved drugs and drug dosages as compared with other American or European countries.
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Cerebrorenal interaction and stroke.
Contrib Nephrol
PUBLISHED: 05-03-2013
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Beyond the original meaning of chronic kidney disease (CKD) as high-risk state for future dialysis, CKD is now known as an established risk factor for cardiovascular diseases. Stroke is a major player of cardiovascular disease and has deep two-way relationships with CKD. CKD is an evident risk factor for stroke. Meta-analyses of cohort studies and trials indicate that proteinuria/albuminuria increases the risk of stroke by 71-92%, and reduced glomerular filtration rate increases the risk by 43%. In addition, CKD has a strong relationship with subclinical brain damage including white matter changes, microbleeds, cognitive impairment, and carotid atherosclerosis. CKD is prevalent in acute stroke patients; patients with estimated glomerular filtration rate <60 ml/min/1.73 m(2) or proteinuria amounted to 46% of total ischemic stroke patients and 39% of total intracerebral hemorrhage patients in our institute. Acute and chronic management of stroke are influenced by CKD. Therapeutic effects of several antithrombotic and thrombolytic agents, including recently-developed novel oral anticoagulants, are affected by renal function. Moreover, reduced glomerular filtration rate is independently associated with increased 1- and 10-year mortalities in the end. Stroke also has deep relationships with end-stage kidney disease. Stroke occurs much more commonly in dialysis patients than general population or CKD patients without need for dialysis. The triggers of ischemic and hemorrhagic stroke in patients with end-stage kidney disease include special characteristics unique to dialysis, such as drastic hemodynamic change, dialysate and anticoagulants, and vascular calcification. As cohorts of dialysis patients become older, more hypertensive, and more diabetic than before, stroke become more prevalent and more serious events in dialysis clinics. Now, clinicians should have much interest in the association between CKD and cerebrovascular diseases, so-called the cerebro-renal interaction.
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Factors Associated with Early Recanalization Failure following Intravenous rt-PA Therapy for Ischemic Stroke.
Cerebrovasc. Dis.
PUBLISHED: 05-02-2013
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Background: Although intravenous recombinant tissue-type plasminogen activator (rt-PA) therapy can be effective for ischemic stroke, a considerable percentage of patients do not receive any benefit as a result of early recanalization failure. We aimed to investigate the factors associated with early recanalization failure following intravenous rt-PA therapy. Methods: Patients with acute ischemic stroke and internal carotid artery (ICA) or middle cerebral artery occlusion on initial magnetic resonance angiography (MRA) who received intravenous rt-PA therapy within 3 h of stroke onset and underwent follow-up MRA within 8 h after treatment were enrolled. Baseline characteristics, stroke features, onset to treatment time, initial National Institutes of Health Stroke Scale (NIHSS) score, initial Alberta Stroke Programme Early CT Score on diffusion-weighted imaging-ASPECTS (Alberta Stroke Program Early Computed Tomography Score), the presence of ICA or M1 origin (the residual length <5 mm) (ICA/M1 origin occlusion), initial vital signs, and laboratory findings were recorded. Early recanalization on the follow-up MRA within 8 h was evaluated by modified Mori grade: grade 0, no reperfusion; grade 1, movement of thrombus; grade 2, partial recanalization, and grade 3, complete recanalization. Results: Seventy subjects (35 women, 77 ± 12 years) were enrolled. The median (interquartile range: IQR) NIHSS score was 18 (12.5-24), and the mean onset to treatment time was 141 ± 54 min. ICA was occluded in 29%, M1 origin in 17%, M1 middle in 13%, M1 distal in 26% and M2 in 15%. The median (IQR) pretreatment diffusion weighted imaging-ASPECTS was 8 (6-9), and follow-up time of MRA was 65 min (59-70) after rt-PA therapy. Thirty-two subjects (46%) showed modified Mori grade 0; 10 (14%), grade 1; 9 (13%), grade 2, and 19 (27%), grade 3. Multivariate analyses revealed ICA/M1 origin occlusion (OR 3.71, 95% CI 1.03-14.87, p = 0.044), and C-reactive protein (per 0.1-mg/dl increment, OR 1.19, 95% CI 1.03-1.44, p = 0.013) were independently associated with subjects with no recanalization (grade 0-1), whereas age (per years old, OR 0.93, 95% CI 0.86-0.99, p = 0.014) and high-density lipoprotein cholesterol (per 1-mg/dl increment, OR 0.94, 95% CI 0.89-0.98, p = 0.004) were inversely associated with those. Conclusion: ICA/M1 origin occlusion and C-reactive protein were positively and high-density lipoprotein cholesterol was negatively associated with early recanalization failure. © 2013 S. Karger AG, Basel.
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Guidelines for the intravenous application of recombinant tissue-type plasminogen activator (alteplase), the second edition, October 2012: a guideline from the Japan Stroke Society.
J Stroke Cerebrovasc Dis
PUBLISHED: 03-26-2013
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In Japan, intravenous alteplase, a recombinant tissue-type plasminogen activator (rt-PA), was approved for an indication of ischemic stroke in 2005 on the basis of the results of a clinical trial with a unique dose of the drug (0.6 mg/kg). The Japan Stroke Society published the guidelines for intravenous application of rt-PA and organized training sessions for proper use all over Japan in an effort to promote the safe, widespread use of intravenous alteplase. Seven years following its approval, clinical experience with intravenous alteplase has accumulated, additional evidence of intravenous alteplase has been found in Japan and overseas, and the medical environment has substantially changed, including approvals for new drugs and medical devices. Notably, the use of alteplase in the extended therapeutic time window (within 4.5 hours of symptom onset) became covered by insurance in Japan in August 2012. To address these changing situations, we have decided to prepare the revised guidelines. In preparing the second edition, we took care to make its contents more practical by emphasizing information needed in clinical practice. While the first edition was developed with emphasis on safety in light of limited clinical experience with intravenous alteplase in Japan in 2005, this second edition is a substantial revision of the first edition mainly in terms of eligibility criteria, on the basis of accumulated evidence and the clinical experience.
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Panmedullary Edema with Inferior Olivary Hypertrophy in Bilateral Medial Medullary Infarction.
J Stroke Cerebrovasc Dis
PUBLISHED: 02-28-2013
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Bilateral medial medullary infarction (MMI) is a rare type of stroke with poor outcomes. Inferior olivary nucleus hypertrophy results from a pathologic lesion in the Guillain-Mollaret triangle. The relationship between inferior olivary nucleus hypertrophy and the medullary lesion is obscure. To the best of our knowledge, only 1 autopsy case with unilateral medial medullary infarction that was associated with ipsilateral inferior olivary nucleus hypertrophy has been reported. We describe a rare case with acute infarction in the bilateral medial medulla oblongata accompanied by subacute bilateral inferior olivary nucleus hypertrophy and panmedullary edema. The hypertrophy appeared to have been caused by local ischemic damage to the termination of the central tegmental tract at the bilateral inferior olivary nucleus.
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The expression level of miR-18b in hepatocellular carcinoma is associated with the grade of malignancy and prognosis.
BMC Cancer
PUBLISHED: 02-27-2013
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Many studies support the hypothesis that specific microRNA (miRNA) expression in various human cancers including hepatocarcinogenesis is closely associated with diagnosis and prognosis. In hepatocellular carcinoma (HCC), malignancy level is related to the degree of histological differentiation.
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Involvement of regulatory interactions among global regulators GlxR, SugR, and RamA in expression of ramA in Corynebacterium glutamicum.
J. Bacteriol.
PUBLISHED: 02-08-2013
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The central carbon metabolism genes in Corynebacterium glutamicum are under the control of a transcriptional regulatory network composed of several global regulators. It is known that the promoter region of ramA, encoding one of these regulators, interacts with its gene product, RamA, as well as with the two other regulators, GlxR and SugR, in vitro and/or in vivo. Although RamA has been confirmed to repress its own expression, the roles of GlxR and SugR in ramA expression have remained unclear. In this study, we examined the effects of GlxR binding site inactivation on expression of the ramA promoter-lacZ fusion in the genetic background of single and double deletion mutants of sugR and ramA. In the wild-type background, the ramA promoter activity was reduced to undetectable levels by the introduction of mutations into the GlxR binding site but increased by sugR deletion, indicating that GlxR and SugR function as the transcriptional activator and repressor, respectively. The marked repression of ramA promoter activity by the GlxR binding site mutations was largely compensated for by deletions of sugR and/or ramA. Furthermore, ramA promoter activity in the ramA-sugR double mutant was comparable to that in the ramA mutant but was significantly higher than that in the sugR mutant. Taken together, it is likely that the level of ramA expression is dynamically balanced by GlxR-dependent activation and repression by RamA along with SugR in response to perturbation of extracellular and/or intracellular conditions. These findings add multiple regulatory loops to the transcriptional regulatory network model in C. glutamicum.
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Epidemiology and Registry Studies of Stroke in Japan.
J Stroke
PUBLISHED: 01-31-2013
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Stroke is the most prevalent cardiovascular disease in Japan. This review introduces two epidemiologic studies and four registry studies of stroke in Japan. The Hisayama Study was begun as a population-based prospective cohort study of cerebrovascular and cardiovascular diseases in 1961 in the town of Hisayama. Most of the deceased subjects of the study underwent autopsy examinations from the beginning of the study. Changes in stroke trends in the last 50 years were clarified by comparison of data from different study cohorts registered every 13 to 14 years. The Suita Study was based on a random sampling of Japanese urban residents. Several reports from this study showed the significance of pre-hypertension, as well as hypertension, as a risk factor for stroke by itself and in combination with other underlying characteristics. In addition, the Japan Multicenter Stroke Investigators Collaboration (J-MUSIC), the Japan Standard Stroke Registry Study, the Fukuoka Stroke Registry, and the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rt-PA Registry are explained as registry studies involving Japanese stroke patients.
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Pegylated interferon monotherapy in patients with chronic hepatitis C with low viremia and its relationship to mutations in the NS5A region and the single nucleotide polymorphism of interleukin-28B.
Hepatol. Res.
PUBLISHED: 01-29-2013
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Previous studies have suggested that patients with chronic hepatitis C with a low pretreatment hepatitis C virus (HCV) level have a high sustained virological response (SVR) rate, and that there would be a subpopulation of patients in which HCV can be eradicated with pegylated interferon (PEG IFN) alone without a decrease in SVR. However, the efficacy of PEG IFN monotherapy in patients with low HCV RNA levels is unclear. Several studies have reported that interferon sensitivity-determining region (ISDR) and the single-nucleotide polymorphism (SNP) of interleukin-28B (IL-28B) contribute to IFN response, but these relationships are controversial. The aim of this study was to determine whether the SNP of IL-28B (rs8099917) and amino acid substitutions in the ISDR among patients with low HCV levels affect the response to PEG IFN monotherapy.
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Oral supplementation with branched-chain amino acid granules prevents hepatocarcinogenesis in patients with hepatitis C-related cirrhosis: A propensity score analysis.
Hepatol. Res.
PUBLISHED: 01-27-2013
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AIM: It has been reported that branched-chain amino acids (BCAA) supplementation can improve nutritional status and reduce liver-related complications in patients with decompensated cirrhosis. BCAA supplementation reportedly reduces the incidence of hepatocellular carcinoma (HCC) in obese cirrhotic patients infected with hepatitis C virus (HCV). We investigated the effects of oral supplementation with BCAA granules on hepatocarcinogenesis in patients with HCV-related cirrhosis using propensity score matching. METHODS: A total of 60 patients with HCV-related cirrhosis and without history of HCC who were selected by one-to-one matching of propensity scores: 30 patients receiving 12?g/day of BCAA granules for 3 months or more (BCAA group) and 30 being observed without BCAA supplementation (control group). The impact of BCAA supplementation was analyzed on the incidence of HCC. RESULTS: The 3- and 5-year rates of HCC development were 13.7% and 13.7% in the BCAA group and 35.1% and 44.5% in the control group, respectively. The BCAA group had a significantly lower rate of HCC than the control group (P?=?0.032). Multivariate analysis for factors that were associated with hepatocarcinogenesis indicated that BCAA supplementation was independently associated with a reduced incidence of HCC (hazard ratio 0.131; 95% confidence interval, 0.032-0.530; P?=?0.004) along with sex and serum ?-fetoprotein. Obesity (body mass index, ?25?kg/m(2) ) was not significantly associated with an increased incidence of HCC. CONCLUSION: Oral supplementation with BCAA granules is associated with a reduced incidence of HCC in patients with HCV-related cirrhosis regardless of the presence of obesity based on the propensity score analysis.
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