Toshiyuki Miyata

National Cerebral and Cardiovascular Center, Ōsaka, Ōsaka, Japan

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Publications (241)657.75 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Severe hypertension (HTN) and acute kidney injury frequently associated with atypical hemolytic uremic syndrome (aHUS) were refractory to various therapies in the pre-eculizumab era. Here we report the case of a 4-month-old boy who developed aHUS presenting with undetectable C3 protein, no predisposing mutations in complement factors, and no antibodies against factor H.
    Pediatric nephrology (Berlin, Germany). 10/2014;
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    ABSTRACT: Despite improvements in therapeutic modalities, the treatment of arterial aneurysms complicating Behçet's disease (BD) is still challenging. This study examined the long-term prognosis after surgery for arterial aneurysms in BD.
    International angiology: a journal of the International Union of Angiology 10/2014; 33(5):419-25. · 1.46 Impact Factor
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    ABSTRACT: There are various angiographic and runoff scoring systems for evaluating stenosis and arterial occlusion in patients with peripheral artery disease (PAD). The report from the BASIL trial revealed that the Bollinger scoring system, originally designed to classify intra-arterial digital subtraction angiography (IADSA), was sensitive to differences in PAD. The purpose of the present study was to evaluate the application of the Bollinger scoring system to a 64-low multidetector computed tomography (MDCT) in PAD patients.
    International angiology: a journal of the International Union of Angiology 10/2014; 33(5):426-33. · 1.46 Impact Factor
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    ABSTRACT: Atypical hemolytic uremic syndrome (aHUS) is caused by abnormalities of the complement system and has a significantly poor prognosis. The clinical phenotypes of 12 patients in nine families with aHUS with familial or recurrent onset and ADAMTS13 activity of ≥20 % treated at the Mie University Hospital were examined. In seven of the patients, the first episode of aHUS occurred during childhood and ten patients experienced a relapse. All patients had renal dysfunction and three had been treated with hemodialysis. Seven patients experienced probable triggering events including common cold, influenza, bacterial infection and/or vaccination for influenza. All patients had entered remission, and renal function was improved in 11 patients. DNA sequencing of six candidate genes, identified a C3 p.I1157T missense mutation in all eight patients in six families examined and this mutation was causative for aHUS. A causative mutation THBD p.D486Y was also identified in an aHUS patient. Four missense mutations, CFH p.V837I, p.Y1058H, p.V1060L and THBD p.R403K may predispose to aHUS manifestation; the remaining seven missense mutations were likely neutral. In conclusion, the clinical phenotypes of aHUS are various, and there are often trigger factors. The C3 p.I1157T mutation was identified as the causative mutation for aHUS in all patients examined, and may be geographically concentrated in or around the Mie prefecture in central Japan.
    International journal of hematology. 08/2014;
  • Haematologica 06/2014; · 5.94 Impact Factor
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    ABSTRACT: Objective To evaluate the outcomes of surgical revascularization for critical limb ischemia in patients with end-stage renal disease (ESRD). Patients and methods From 2004 to 2010, 184 patients with 213 critically ischaemic limbs caused by arteriosclerosis were admitted to The University of Tokyo Hospital. The outcomes of primarily surgical revascularization-based treatments were retrospectively compared in patients with ESRD (ESRD group: 79 patients, 101 limbs) and without ESRD (non-ESRD group: 105 patients, 112 limbs) during the same period. Results Arterial reconstruction was performed on 56 limbs in 46 patients in the ESRD group and 78 limbs in 73 patients in the non-ESRD group (55% vs. 70%; p = .03). Major amputation was performed in 6 of 48 limbs with patent grafts in the ESRD group because of uncontrolled infection or progression of necrosis. The limb salvage rate after arterial reconstruction was significantly lower in the ESRD group than in the non-ESRD group (p = .0019). The postoperative survival rate was lower in the ESRD group than in the non-ESRD group, although this difference was not significant (p = .052). Associated cardiovascular disease and systemic infection were the most frequent causes of death in the ESRD group. There was no significant difference in graft patency between the two groups after distal bypass surgery; however, the limb salvage rate was significantly lower in the ESRD group than in the non-ESRD group (p = .03). Conclusions Critical limb ischemia associated with ESRD has a poor prognosis. Infection control is particularly important for achievement of good treatment outcomes.
    European Journal of Vascular and Endovascular Surgery. 01/2014;
  • [Rinshō ketsueki] The Japanese journal of clinical hematology 01/2014; 55(1):93-104.
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    ABSTRACT: Direct sequencing is a popular method to discover mutations in candidate genes responsible for hereditary diseases. A certain type of mutation, however, can be missed by the method. Here, we report a comprehensive genomic quantitative polymerase chain reaction (qPCR) to complement the weakness of direct sequencing. Upshaw-Schulman syndrome (USS) is a recessively inherited disease associated with severe deficiency of plasma ADAMTS13 activity. We previously analyzed ADAMTS13 in 47 USS patients using direct sequencing, and 44 of them had either homozygous or compound heterozygous mutations. Then, we sought to reveal more extensive defects of ADAMTS13 in the remaining three patients. We quantified copy numbers of each ADAMTS13 exon in the patients by using genomic qPCR. Each primer pair was designed to contain at least one of the two primers used in direct sequencing, to avoid missing any exonic deletions. The qPCR demonstrated heterozygous loss of exons 7 and 8 in one patient and exon 27 in the other, and further analysis revealed c.746_987+373del1782 and c.3751_3892+587del729, respectively. Genomic qPCR provides an effective method for identifying extensive defects of the target genes.
    Molecular Genetics & Genomic Medicine. 01/2014;
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    ABSTRACT: Background Hereditary thrombophilias may associate with uteroplacental thrombosis leading to adverse pregnancy outcomes. The present study was conducted to reveal the frequency of the low-frequency thrombophilic protein S K196E mutation, as well as the frequency of very rare nonsynonymous mutations in protein S, protein C, and antithrombin genes, in patients with adverse pregnancy outcomes. Patients and methods We enrolled 330 Japanese patients with adverse pregnancy outcomes and divided them into 233 patients with two or more miscarriages and 114 patients with fetal growth restriction (FGR) and/or intrauterine fetal death (IUFD); 17 patients belonged to both groups. We sequenced the entire coding regions of three anticoagulant genes in all 330 patients. Results We found that protein S K196E mutation was identified in 4 out of 233 patients with recurrent miscarriage and in 2 out of 114 patients with FGR and/or IUFD. The frequencies of this mutation in these patient groups were not different from that in a Japanese general population. Very rare nonsynonymous mutations were identified in 3.3% (11 out of 330) of patients with adverse pregnancy outcomes. Conclusions Although the low-frequency protein S K196E mutation can increase the risk for venous thromboembolism, it did not increase the risk for adverse pregnancy outcomes even in Japanese.
    Thrombosis Research 01/2014; · 3.13 Impact Factor
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    Tong Yin, Toshiyuki Miyata
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    ABSTRACT: Venous thromboembolism (VTE) is a life-threatening medical disorder worldwide. A great deal of evidence suggests that prevalence of VTE varies significantly among ethnic populations, with consistently lower incidence found in Asians. While the distribution of genetic risk factors may vary among races, genetic risk factors can play a major role among individuals with different genetic backgrounds. Two clinically evaluated low-frequency genetic mutations that predispose to VTE-the factor V Leiden mutation and prothrombin G20210A mutation-are found predominantly in Caucasians, and virtually never in Asians. The findings of a recent genetic study of VTE in northeast Asians, which greatly advanced our knowledge in this area, indicate that the most frequent genetic risk factors for VTE in northeast Asians can be attributed to a dysfunction of the protein C anticoagulant system. Several low-frequency genetic mutations, PROS1 p.Lys196Glu in Japanese and PROC p.Arg189Trp and p.Lys193del in Chinese, are significantly associated with increased risk for VTE, with odds ratio more than 2 through the reduced protein C anticoagulant activity. Construction of a multifactorial model based on the genetic risk factors in the protein C anticoagulant system could facilitate genetic counseling for VTE risk in these populations. The influence of prevalent genetic mutations on the risk of VTE should be further investigated in Asian countries.
    Journal of Thrombosis and Thrombolysis 11/2013; · 1.99 Impact Factor
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    ABSTRACT: Background: Patients with mild-to-moderate essential hypertension in the HOMED-BP trial were randomly allocated to first-line treatment with a calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). Methods: We recruited 265 (93 for CCB, 71 for ACEI and 101 for ARB) patients who completed the genomic study. Home blood pressure was measured for 5 days off-treatment before randomization and for 5 days after 2-4 weeks of randomized drug treatment. Genotyping was performed by 500K DNA microarray chips. The blood pressure responses to the three drugs were analyzed separately as a quantitative trait. For replication of SNPs with p < 10(-4), we used the multicenter GEANE study, in which patients were randomized to valsartan or amlodipine. Results: SNPs in PICALM, TANC2, NUMA1 and APCDD1 were found to be associated with CCB responses and those in ABCC9 and YIPF1 were found to be associated with ARB response with replication. Conclusion: Our approach, the first based on high-fidelity phenotyping by home blood pressure measurement, might be a step in moving towards the personalized treatment of hypertension. Original submitted 29 April 2013; Revision submitted 14 August 2013.
    Pharmacogenomics 11/2013; 14(14):1709-21. · 3.86 Impact Factor
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    ABSTRACT: Aim: In Trans-Atlantic Inter-Society Concensus (TASC) II, patients at risk for critical limb ischemia (CLI) without symptoms are termed "chronic subclinical ische mia," but research are still lacking. The objective was to find out whether clinically asymptomatic contralateral limbs at the time of treatment for ipsilateral CLI could be regarded as "chronic subclinical ischemia". Methods: Ninety-six patients with CLI who had no symptoms in the contralateral limb were retrospectively reviewed. The symptoms of the contralateral limb after initial intervention for the ipsilateral limb were surveyed. Risk factors for developing CLI and tissue loss were then analyzed. Results: Five patients (5.2%) became claudicants, 37 patients (38.5%) had symptoms of CLI, and 14 (14.6%) experienced tissue loss during the follow-up period. The overall CLI-free rates at 12, 36, and 60 months were 79.2%, 55.2%, and 45.8%, respectively, while the tissue loss-free rates at 12, 36, and 60 months were 91.3%, 78.8%, and 78.8%, respectively. Risk factor for developing CLI on the contralateral limb was having skin perfusion pressure (SPP) <40 mmHg at the surgery for ipsilateral limb. The presence of SPP <40 mmHg and end stage renal failure with hemodialysis resulted in a significantly high probability of tissue loss. Conclusion: Patients with CLI with an asymptomatic contralateral limb with an SPP value <40 mmHg are at a high risk of developing CLI and tissue loss during the follow-up period. Information on the contralateral limb at initial surgery may help to speculate the fate of the asymptomatic contralateral limb.
    International angiology: a journal of the International Union of Angiology 10/2013; 32(5):526-31. · 1.46 Impact Factor
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    ABSTRACT: Thrombotic thrombocytopenic purpura (TTP) is frequently associated with renal abnormalities, but there have been few reports about renal abnormalities in patients with hereditary TTP. In particular, little is known about the long-term prognosis of patients with childhood-onset congenital TTP. We report a Japanese patient with congenital TTP (Upshaw--Schulman syndrome) who was followed for 19 years after initiation of hemodialysis when he was 22 years old. At the age of 6 years, the first episode of purpura, thrombocytopenia, and proteinuria occurred without any precipitating cause. He underwent living-related donor kidney transplantation from his mother, but the graft failed after 5 months due to recurrence of TTP. Even after resection of the transplanted kidney and resumption of regular hemodialysis, TTP became refractory to infusion of fresh frozen plasma (FFP). Therefore, splenectomy was performed and his disease remained in remission for 10 years. However, TTP recurred at the age of 39 years. Plasma activity of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I domain 13) was less than 3%, while ADAMTS13 inhibitor was not detected (< 0.5 Bethesda units/mL). The patient died suddenly after hemodialysis at the age of 41 years. Subsequent genetic analysis of this patient and his parents revealed two different heterozygous mutations of ADAMTS13, including a missense mutation in exon 26 (c.T3650C causing p.I1217T) inherited from his father and a missense mutation in exon 21 (c.G2723A causing p.C908Y) inherited from his mother. The former mutation has not been detected before in Japan, while the latter mutation is common in Japan. A retrospective review showed that serum C3 levels were consistently low while C4 levels were normal during follow-up, and C3 decreased much further during each episode of TTP. Congenital TTP was diagnosed from the clinical, biochemical, and genetic findings. Infusion of FFP controlled each thrombotic episode, but the effect was limited and of short duration. Review of the complement profile in this patient suggested that a persistently low serum C3 level might be associated with refractory TTP and a worse renal prognosis.
    BMC Nephrology 07/2013; 14(1):156. · 1.64 Impact Factor
  • Blood transfusion = Trasfusione del sangue 07/2013; · 1.86 Impact Factor
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    ABSTRACT: How hematopoietic stem cells (HSCs) produce particular lineages is insufficiently understood. We searched for key factors that direct HSC to lymphopoiesis. Comparing gene expression profiles for HSCs and early lymphoid progenitors revealed that Satb1, a global chromatin regulator, was markedly induced with lymphoid lineage specification. HSCs from Satb1-deficient mice were defective in lymphopoietic activity in culture and failed to reconstitute T lymphopoiesis in wild-type recipients. Furthermore, Satb1 transduction of HSCs and embryonic stem cells robustly promoted their differentiation toward lymphocytes. Whereas genes that encode Ikaros, E2A, and Notch1 were unaffected, many genes involved in lineage decisions were regulated by Satb1. Satb1 expression was reduced in aged HSCs with compromised lymphopoietic potential, but forced Satb1 expression partly restored that potential. Thus, Satb1 governs the initiating process central to the replenishing of lymphoid lineages. Such activity in lymphoid cell generation may be of clinical importance and useful to overcome immunosenescence.
    Immunity 06/2013; · 19.80 Impact Factor
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    ABSTRACT: Resveratrol, a polyphenolic phytoalexin found in red wine and various plants, has been reported to up-regulate the expression of endothelial NO synthase (eNOS) in human umbilical vein endothelial cells (HUVEC). However, this effect was neither long term in nature nor physiologically relevant at the concentration of resveratrol studied. In the present study, we investigated the effects of repeated treatments with a lower concentration of resveratrol on the expression of genes in HUVEC. The expression levels of eNOS and silent mating type information regulation 2 homologue 1 (SIRT1) were up-regulated in HUVEC by repeated treatments with 1 μm-resveratrol for 6 d, but not with fenofibrate. Moreover, resveratrol treatment increased the expression of autophagy-regulated genes such as γ-aminobutyric acid A receptor-associated protein (GABARAP), microtubule-associated protein 1 light chain 3B (LC3B) and autophagy-related protein 3 (ATG3), the radical scavenger activity-related metallothionein-1X (MT1X) gene and the anti-inflammatory activity-related annexin A2 (ANXA) gene. In addition, resveratrol treatment down-regulated the expression of the cell-cycle checkpoint control RAD9 homologue B (RAD9B) gene. These results indicate the beneficial effects of resveratrol on the cardiovascular system.
    The British journal of nutrition 06/2013; · 3.45 Impact Factor
  • Thrombosis Research 05/2013; · 3.13 Impact Factor
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    ABSTRACT: Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Approximately 10% of cases are classified as atypical due to the absence of Shiga toxin-producing bacteria as a trigger. Uncontrolled activation of the complement system plays a role in the pathogenesis of atypical HUS (aHUS). Although many genetic studies on aHUS have been published in recent years, only limited data has been gathered in Asian countries. We analyzed the genetic variants of 6 candidate genes and the gene deletion in complement factor H (CFH) and CFH-related genes, examined the prevalence of CFH autoantibodies and evaluated the genotype-phenotype relationship in 10 Japanese patients with aHUS. We identified 7 causative or potentially causative mutations in CFH (p.R1215Q), C3 (p.R425C, p.S562L, and p.I1157T), membrane cofactor protein (p.Y189D and p.A359V) and thrombomodulin (p.T500M) in 8 out of 10 patients. All 7 of the mutations were heterozygous and four of them were novel. Two patients carried CFH p.R1215Q and 3 other patients carried C3 p.I1157T. One patient had 2 causative mutations in different genes. One patient was a compound heterozygote of the 2 MCP mutations. The patients carrying mutations in CFH or C3 had a high frequency of relapse and a worse prognosis. One patient had CFH autoantibodies. The present study identified the cause of aHUS in 9 out of 10 Japanese patients. Since the phenotype-genotype correlation of aHUS has clinical significance in predicting renal recovery and transplant outcome, a comprehensively accurate assessment of molecular variation would be necessary for the proper management of aHUS patients in Japan.
    Molecular Immunology 01/2013; 54(2):238-246. · 2.65 Impact Factor
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    ABSTRACT: Integrin-linked kinase (ILK) is an important signaling regulator that assembles into the heteroternary complex with adaptor proteins PINCH and parvin (termed the IPP complex). We recently reported that ILK is important for integrin activation in a Chinese hamster ovary (CHO) cell system. We previously established parental CHO cells expressing a constitutively active chimeric integrin (αIIbα6Bβ3) and mutant CHO cells expressing inactive αIIbα6Bβ3 due to ILK deficiency. In this study, we further investigated the underlying mechanisms for ILK-dependent integrin activation. ILK-deficient mutant cells had trace levels of PINCH and α-parvin, and transfection of ILK cDNA into the mutant cells increased not only ILK but also PINCH and α-parvin, resulting in the restoration of αIIbα6Bβ3 activation. In the parental cells expressing active αIIbα6Bβ3, ILK, PINCH, and α-parvin were co-immunoprecipitated, indicating the formation of the IPP complex. Moreover, short interfering RNA (siRNA) experiments targeting PINCH-1 or both α- and β-parvin mRNA in the parent cells impaired the αIIbα6Bβ3 activation as well as the expression of the other components of the IPP complex. In addition, ILK mutants possessing defects in either PINCH or parvin binding failed to restore αIIbα6Bβ3 activation in the mutant cells. Kindlin-2 siRNA in the parental cells impaired αIIbα6Bβ3 activation without disturbing the expression of ILK. For CHO cells stably expressing wild-type αIIbβ3 that is an inactive form, overexpression of a talin head domain (THD) induced αIIbβ3 activation and the THD-induced αIIbβ3 activation was impaired by ILK siRNA through a significant reduction in the expression of the IPP complex. In contrast, overexpression of all IPP components in the αIIbβ3-expressing CHO cells further augmented THD-induced αIIbβ3 activation, whereas they did not induce αIIbβ3 activation without THD. These data suggest that the IPP complex rather than ILK plays an important role and supports integrin activation probably through stabilization of the active conformation.
    PLoS ONE 01/2013; 8(12):e85498. · 3.53 Impact Factor

Publication Stats

3k Citations
657.75 Total Impact Points


  • 1998–2014
    • National Cerebral and Cardiovascular Center
      • Department of Cardiovascular Medicine
      Ōsaka, Ōsaka, Japan
  • 2013
    • Aiiku Hospital
      Edo, Tōkyō, Japan
  • 2011–2013
    • 307 Hospital of the Chinese People's Liberation Army
      Peping, Beijing, China
  • 1990–2013
    • The University of Tokyo
      • • Department of Vascular Surgery
      • • Faculty & Graduate School of Medicine
      • • Department of Surgical Sciences
      • • Division of Surgery
      Tokyo, Tokyo-to, Japan
  • 2010
    • Tokyo Medical University
      • Division of Cardiovascular Surgery
      Edo, Tōkyō, Japan
  • 2007
    • Osaka City University
      • Department of Cardiovascular Medicine
      Ōsaka, Ōsaka, Japan
  • 2005–2006
    • Kyushu University
      • • Department of Biology
      • • Faculty of Sciences
      Hukuoka, Fukuoka, Japan
  • 2004
    • Nara Medical University
      Kashihara, Nara, Japan
  • 2003
    • Osaka City General Hospital
      Ōsaka, Ōsaka, Japan
  • 2001
    • Asahi General Hospital
      Asahi, Chiba, Japan
  • 1999
    • Saitama Medical University
      • Department of Surgery
      Saitama, Saitama-ken, Japan