Publications by authors named "Tatsuyuki Sato"

23 Publications

  • Page 1 of 1

Hyperpolarized C Magnetic Resonance Imaging as a Tool for Imaging Tissue Redox State, Oxidative Stress, Inflammation, and Cellular Metabolism.

Antioxid Redox Signal 2021 Aug 17. Epub 2021 Aug 17.

Division of Bioengineering & Bioinformatics, Graduate School of Information Science & Technology, Hokkaido University, Sapporo, Japan.

Magnetic resonance imaging (MRI) with hyperpolarized (HP) C-labeled redox-sensitive metabolic tracers can provide noninvasive functional imaging biomarkers, reflecting tissue redox state, oxidative stress, and inflammation, among others. The capability to use endogenous metabolites as C-enriched imaging tracers without structural modification makes HP C MRI a promising tool to evaluate redox state in patients with various diseases. Recent studies have demonstrated the feasibility of metabolic imaging of C-labeled tracers polarized by parahydrogen-induced polarization techniques, which offer a cost-effective alternative to the more widely used dissolution dynamic nuclear polarization-based hyperpolarizers. Although the fluxes of many metabolic pathways reflect the change in tissue redox state, they are not functionally specific. In the present review, we summarize recent challenges in the development of specific C metabolic tracers for biomarkers of redox state, including that for detecting reactive oxygen species. Applications of HP C metabolic MRI to evaluate redox state have only just begun to be investigated. The possibility to gain a comprehensive understanding of the correlations between tissue redox potential and metabolism under different pathological conditions by using HP C MRI is promoting its interest in the clinical arena, along with its noninvasive biomarkers to evaluate the extent of disease and treatment response.
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http://dx.doi.org/10.1089/ars.2021.0139DOI Listing
August 2021

Small Dense Low-Density Lipoprotein Cholesterol is a Potential Marker for Predicting Laser Treatment for Retinopathy in Diabetic Patients.

J Atheroscler Thromb 2021 May 14. Epub 2021 May 14.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo.

Aim: We explored the superiority of small dense low-density lipoprotein cholesterol (sdLDL-C) as a marker for predicting not only the occurrence of cardiovascular (CV) events but also the need for laser treatment in patients with hypercholesterolemia and diabetic retinopathy.

Methods: We performed a sub-analysis of the intEnsive statin therapy for hyper-cholesteroleMic Patients with diAbetic retinopaTHY (EMPATHY) study (n=5042), in which patients were assigned randomly to intensive or standard statin therapy targeting low-density lipoprotein cholesterol <70 mg/dl or 100-120 mg/dl. Using the survival analysis, the risks for CV events and the need for laser treatment were evaluated according to the lipids one year after registration.

Results: The patients were 63±11 years old. LDL-C and sdLDL-C levels were 98±25 and 32±14 mg/dl, respectively, one year after registration. The sdLDL-C level had a strong positive correlation with apolipoprotein B level (r=0.83 at registration). SdLDL-C was a sensitive marker for predicting CV events when comparing among the quartiles according to sdLDL-C levels (hazard ratios: HR for quartiles 1-4 were 1.0, 1.4, 1.6, and 2.5, respectively; p for trend <0.01). Also, sdLDL-C was a sensitive marker for predicting the need for laser treatment among lipids (log rank, p=0.009), especially in patients with elderly (≧65 yrs) and obesity (BMI ≧25 kg/m).

Conclusions: SdLDL-C is a sensitive target marker to predict cardiovascular events as well as the need for laser treatment in patients with hypercholesterolemia and diabetic retinopathy.
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http://dx.doi.org/10.5551/jat.62889DOI Listing
May 2021

Mutant KRAS drives metabolic reprogramming and autophagic flux in premalignant pancreatic cells.

Cancer Gene Ther 2021 Apr 8. Epub 2021 Apr 8.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.

Mutational activation of the KRAS gene occurs in almost all pancreatic ductal adenocarcinoma (PDAC) and is the earliest molecular event in their carcinogenesis. Evidence has accumulated of the metabolic reprogramming in PDAC, such as amino acid homeostasis and autophagic flux. However, the biological effects of KRAS mutation on metabolic reprogramming at the earlier stages of PDAC carcinogenesis are unclear. Here we report dynamic metabolic reprogramming in immortalized human non-cancerous pancreatic ductal epithelial cells, in which a KRAS mutation was induced by gene-editing, which may mimic early pancreatic carcinogenesis. Similar to the cases of PDAC, KRAS gene mutation increased the dependency on glucose and glutamine for maintaining the intracellular redox balance. In addition, the intracellular levels of amino acids were significantly decreased because of active protein synthesis, and the cells required greater autophagic flux to maintain their viability. The lysosomal inhibitor chloroquine significantly inhibited cell proliferation. Therefore, metabolic reprogramming is an early event in carcinogenesis initiated by KRAS gene mutation, suggesting a rationale for the development of nutritional interventions that suppress or delay the development of PDAC.
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http://dx.doi.org/10.1038/s41417-021-00326-4DOI Listing
April 2021

Fibroblast-Cardiomyocyte Interaction in Pediatric Restrictive Cardiomyopathy.

Circ J 2021 04 6;85(5):687-689. Epub 2021 Mar 6.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo.

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http://dx.doi.org/10.1253/circj.CJ-21-0100DOI Listing
April 2021

CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor.

Sci Rep 2021 Feb 9;11(1):3426. Epub 2021 Feb 9.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Most seven transmembrane receptors (7TMRs) are G protein-coupled receptors; however, some 7TMRs evoke intracellular signals through β-arrestin as a biased receptor. As several β-arrestin-biased agonists have been reported to be cardioprotective, we examined the role of the chemokine receptor CXCR7 as a β-arrestin-biased receptor in the heart. Among 510 7TMR genes examined, Cxcr7 was the most abundantly expressed in the murine heart. Single-cell RNA-sequencing analysis revealed that Cxcr7 was abundantly expressed in cardiomyocytes and fibroblasts. Cardiomyocyte-specific Cxcr7 null mice showed more prominent cardiac dilatation and dysfunction than control mice 4 weeks after myocardial infarction. In contrast, there was no difference in cardiac phenotypes between fibroblast-specific Cxcr7-knockout mice and control mice even after myocardial infarction. TC14012, a specific agonist of CXCR7, significantly recruited β-arrestin to CXCR7 in CXCR7-expressing cells and activated extracellular signal-regulated kinase (ERK) in neonatal rat cardiomyocytes. Cxcr7 expression was significantly increased and ERK was activated in the border zone of the heart in control, but not Cxcr7 null mice. These results indicate that the abundantly expressed CXCR7 in cardiomyocytes may play a protective role in the heart as a β-arrestin-biased receptor and that CXCR7 may be a novel therapeutic target for myocardial infarction.
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http://dx.doi.org/10.1038/s41598-021-83022-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873251PMC
February 2021

Clinical importance of respiratory muscle fatigue in patients with cardiovascular disease.

Medicine (Baltimore) 2020 Aug;99(34):e21794

Department of Cardiovascular Medicine, Graduate School of Medicine, the University of Tokyo.

Patients with cardiovascular diseases frequently experience exertional dyspnea. However, the relationship between respiratory muscle strength including its fatigue and cardiovascular dysfunctions remains to be clarified.The maximal inspiratory pressure/maximal expiratory pressure (MIP/MEP) before and after cardiopulmonary exercise testing (CPX) in 44 patients with heart failure and ischemic heart disease were measured. Respiratory muscle fatigue was evaluated by calculating MIP (MIPpost/MIPpre) and MEP (MEPpost/MEPpre) changes.The mean MIPpre and MEPpre values were 67.5 ± 29.0 and 61.6 ± 23.8 cm H2O, respectively. After CPX, MIP decreased in 25 patients, and MEP decreased in 22 patients. We evaluated the correlation relationship between respiratory muscle function including respiratory muscle fatigue and exercise capacity evaluated by CPX such as peak VO2 and VE/VCO2 slope. Among MIP, MEP, change in MIP, and change in MEP, only the value of change in MIP had an association with the value of VE/VCO2 slope (R = -0.36, P = .017). In addition, multivariate analysis for determining factor of change in MIP revealed that the association between the change in MIP and eGFR was independent from other confounding parameters (beta, 0.40, P = .017). The patients were divided into 2 groups, with (MIP change < 0.9) and without respiratory muscle fatigue (MIP change > 0.9), and a significant difference in peak VO2 (14.2 ± 3.4 [with fatigue] vs 17.4 ± 4.7 [without fatigue] mL/kg/min; P = .020) was observed between the groups.Respiratory muscle fatigue demonstrated by the change of MIP before and after CPX significantly correlated with exercise capacity and renal function in patients with cardiovascular disease.
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http://dx.doi.org/10.1097/MD.0000000000021794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447364PMC
August 2020

Lipid-lowering statin therapy is beneficial in elderly female patients with hypercholesterolaemia and diabetic retinopathy.

Eur J Prev Cardiol 2020 Apr 27:2047487320920761. Epub 2020 Apr 27.

Department of Cardiovascular Medicine, The University of Tokyo, Japan.

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http://dx.doi.org/10.1177/2047487320920761DOI Listing
April 2020

Noonan syndrome-associated biallelic LZTR1 mutations cause cardiac hypertrophy and vascular malformations in zebrafish.

Mol Genet Genomic Med 2020 03 28;8(3):e1107. Epub 2019 Dec 28.

Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Variants in the LZTR1 (leucine-zipper-like transcription regulator 1) gene (OMIM #600574) have been reported in recessive Noonan syndrome patients. In vivo evidence from animal models to support its causative role is lacking.

Methods: By CRISPR-Cas9 genome editing, we generated lztr1-mutated zebrafish (Danio rerio). Analyses of histopathology and downstream signaling were performed to investigate the pathogenesis of cardiac and extracardiac abnormalities in Noonan syndrome.

Results: A frameshift deletion allele was created in the zebrafish lztr1. Crosses of heterozygotes obtained homozygous lztr1 null mutants that modeled LZTR1 loss-of-function. Histological analyses of the model revealed ventricular hypertrophy, the deleterious signature of Noonan syndrome-associated cardiomyopathy. Further, assessment for extracardiac abnormalities documented multiple vascular malformations, resembling human vascular pathology caused by RAS/MAPK activation. Due to spatiotemporal regulation of LZTR1, its downstream function was not fully elucidated from western blots of adult tissue.

Conclusion: Our novel zebrafish model phenocopied human recessive Noonan syndrome and supported the loss-of-function mechanism of disease-causing LZTR1 variants. The discovery of vascular malformations in mutants calls for the clinical follow-up of patients to monitor for its emergence. The model will serve as a novel platform for investigating the pathophysiology linking RAS/MAPK signaling to cardiac and vascular pathology.
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http://dx.doi.org/10.1002/mgg3.1107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057116PMC
March 2020

Therapeutic targeting of mitochondrial ROS ameliorates murine model of volume overload cardiomyopathy.

J Pharmacol Sci 2019 Sep 28;141(1):56-63. Epub 2019 Sep 28.

Department of Cardiac Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Concomitant heart failure is associated with poor clinical outcome in dialysis patients. The arteriovenous shunt, created as vascular access for hemodialysis, increases ventricular volume-overload, predisposing patients to developing cardiac dysfunction. The integral function of mitochondrial respiration is critically important for the heart to cope with hemodynamic overload. The involvement, however, of mitochondrial activity or reactive oxygen species (ROS) in the pathogenesis of ventricular-overload-induced heart failure has not been fully elucidated. We herein report that disorganization of mitochondrial respiration increases mitochondrial ROS production in the volume-overloaded heart, leading to ventricular dysfunction. We adopted the murine arteriovenous fistula (AVF) model, which replicates the cardinal features of volume-overload-induced ventricular dysfunction. Enzymatic assays of cardiac mitochondria revealed that the activities of citrate synthase and NADH-quinone reductase (complex Ⅰ) were preserved in the AVF heart. In contrast, the activity of NADH oxidase supercomplex was significantly compromised, resulting in elevated ROS production. Importantly, the antioxidant N-acetylcysteine prevented the development of ventricular dilatation and cardiac dysfunction, suggesting a pathogenic role for ROS in dialysis-related cardiomyopathy. A cardioprotective effect was also observed in metformin-treated mice, illuminating its potential use in the management of heart failure complicating diabetic patients on dialysis.
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http://dx.doi.org/10.1016/j.jphs.2019.09.005DOI Listing
September 2019

Cell Cycle Perturbation Induces Collagen Production in Fibroblasts.

Int Heart J 2019 Jul 12;60(4):958-963. Epub 2019 Jul 12.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo.

Myocardial infarction (MI) occurs when the heart muscle is severely damaged due to a decrease in blood flow from the coronary arteries. During recovery from an MI, cardiac fibroblasts become activated and produce extracellular matrices, contributing to the wound healing process in the damaged heart. Inappropriate activation of the fibroblasts leads to excessive fibrosis in the heart. However, the molecular pathways by which cardiac fibroblasts are activated have not yet been fully elucidated.Here we show that serum deprivation, which recapitulates the cellular microenvironment of the MI area, strikingly induces collagen production in C3H/10T1/2 cells. Based on transcriptomic and pharmacological studies, we found that cell cycle perturbation is directly linked to collagen production in fibroblasts. Importantly, collagen synthesis is increased independently of the transcriptional levels of type I collagen genes. These results reveal a novel mode of fibroblast activation in the ischemic area, which will allow us to gain insights into the molecular mechanisms underlying cardiac fibrosis and establish a basis for anti-fibrotic therapy.
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http://dx.doi.org/10.1536/ihj.18-710DOI Listing
July 2019

Macrophage hypoxia signaling regulates cardiac fibrosis via Oncostatin M.

Nat Commun 2019 06 27;10(1):2824. Epub 2019 Jun 27.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

The fibrogenic response in tissue-resident fibroblasts is determined by the balance between activation and repression signals from the tissue microenvironment. While the molecular pathways by which transforming growth factor-1 (TGF-β1) activates pro-fibrogenic mechanisms have been extensively studied and are recognized critical during fibrosis development, the factors regulating TGF-β1 signaling are poorly understood. Here we show that macrophage hypoxia signaling suppresses excessive fibrosis in a heart via oncostatin-m (OSM) secretion. During cardiac remodeling, Ly6C monocytes/macrophages accumulate in hypoxic areas through a hypoxia-inducible factor (HIF)-1α dependent manner and suppresses cardiac fibroblast activation. As an underlying molecular mechanism, we identify OSM, part of the interleukin 6 cytokine family, as a HIF-1α target gene, which directly inhibits the TGF-β1 mediated activation of cardiac fibroblasts through extracellular signal-regulated kinase 1/2-dependent phosphorylation of the SMAD linker region. These results demonstrate that macrophage hypoxia signaling regulates fibroblast activation through OSM secretion in vivo.
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http://dx.doi.org/10.1038/s41467-019-10859-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597788PMC
June 2019

Successful Transvenous Pacemaker Implantation via Re-Directed Left Superior Vena Cava.

Circ J 2019 09 29;83(10):2082. Epub 2019 Mar 29.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo.

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http://dx.doi.org/10.1253/circj.CJ-19-0010DOI Listing
September 2019

Neuregulin-4, an Adipokine, as a Residual Risk Factor of Atherosclerotic Coronary Artery Disease.

Int Heart J 2019 ;60(1):1-3

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo.

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http://dx.doi.org/10.1536/ihj.18-654DOI Listing
July 2019

Prevalence of primary Sjögren's syndrome in patients undergoing evaluation for pulmonary arterial hypertension.

PLoS One 2018 15;13(5):e0197297. Epub 2018 May 15.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: The prevalence of pulmonary arterial hypertension (PAH) in primary Sjögren's syndrome (SS) had been reported to be rare. However, recent studies using echocardiography as a screening method showed conflicting results, and the true prevalence is still unclear. Since diagnosing primary SS is difficult because of its heterogeneous nature, a number of patients with primary-SS-associated PAH may be misdiagnosed with idiopathic PAH, losing their chance to undergo immunosuppressive therapy. Therefore, we sought to elucidate the prevalence of primary SS among patients who initially present with PAH.

Methods: From our prospective institutional PAH database, 40 consecutive patients without any obvious cause of PAH at the time of PAH diagnosis were identified. We retrospectively evaluated the prevalence of primary SS diagnosed during or after the initial assessment of PAH.

Results: During the initial assessment, one patient was diagnosed with primary-SS-associated PAH. Among the 25 patients who were initially diagnosed with idiopathic PAH, five were diagnosed with primary SS during their course of the disease. Of the five patients, three had key signs suggesting primary SS and were probably underdiagnosed at the time of initial evaluation. The remaining two patients, who were finally diagnosed with primary SS, did not have any specific signs suggesting primary SS at the time of initial evaluation but showed positive conversion of their autoantibodies during the course of PAH.

Conclusion: The prevalence of primary-SS-associated PAH may be relatively high among patients who undergo initial evaluation for PAH. Furthermore, primary-SS-associated PAH may be underdiagnosed with routine evaluation for the primary cause of PAH. Clinicians should pay specific attention and carefully evaluate the possibility of primary SS in patients with PAH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197297PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953489PMC
November 2018

Pulmonary Tumor Thrombotic Microangiopathy due to Advanced Gastric Cancer with Virchow's Node Metastasis.

Int Heart J 2018 Mar 5;59(2):443-447. Epub 2018 Mar 5.

Division of Cardiology, Mitsui Memorial Hospital.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal cancer-related complication characterized by severe progressive pulmonary hypertension. Antemortem diagnosis is difficult owing to the rapid progression of the condition, especially when the patient has no known malignancies and initially presents with pulmonary hypertension. Here we report a case of PTTM due to occult gastric cancer with metastasis in the left supraclavicular lymph node, also known as Virchow's node. Enlarged Virchow's node is an important indicator of advanced gastric cancer. In patients with progressive pulmonary hypertension of unknown origin, enlarged Virchow's node can be an important indicator for the diagnosis of PTTM.
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http://dx.doi.org/10.1536/ihj.17-249DOI Listing
March 2018

Impact of Serum Phosphorus Levels on Outcomes After Implantation of Drug-Eluting Stents in Patients on Hemodialysis.

Circ J 2018 01 20;82(2):388-395. Epub 2017 Oct 20.

Division of Cardiology, Tokai University School of Medicine.

Background: Elevated serum phosphorus level is an important risk factor for cardiovascular death in general patients on hemodialysis (HD). However, the effect of serum phosphorus levels on outcomes after drug-eluting stent (DES) implantation in HD patients is unknown.Methods and Results:This was a post-hoc study of the OUCH study series, a series of prospective multicenter registries of HD patients who underwent DES implantation comprising 359 patients from 31 centers in Japan. Patients were categorized into 3 groups according to their preprocedural serum phosphorus levels. The 1-year clinical outcomes of the 336 patients treated for de novo lesions were evaluated. Compared with patients with high (>5.5 mg/dL; n=65) or normal (3.5-5.5 mg/dL; n=219) serum phosphorus levels, those with low serum phosphorus levels (<3.5 mg/dL; n=52) had significantly fewer target lesion revascularization events (13.9% vs. 16.9% vs. 1.9%; P=0.0090) and major adverse cardiac and cerebrovascular events (29.2% vs. 31.1% vs. 13.5%; P=0.032). Multivariate logistic regression analysis revealed that low serum phosphorus level was an independent negative predictor for major adverse cardiac and cerebrovascular events (adjusted odds ratio, 0.31; 95% confidence interval, 0.12-0.70; P=0.0036).

Conclusions: Lowering of serum phosphorus levels beyond the current recommended range may be considered in HD patients who undergo DES implantation.
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http://dx.doi.org/10.1253/circj.CJ-17-0649DOI Listing
January 2018

Rapid Improvement of thyroid storm-related hemodynamic collapse by aggressive anti-thyroid therapy including steroid pulse: A case report.

Medicine (Baltimore) 2017 Jun;96(22):e7053

Department of Cardiovascular Medicine Department of Therapeutic Strategy for Heart Failure Department of Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Rationale: Heart failure is relatively common in patients with hyperthyroidism, but thyrotoxic cardiomyopathy with poor left ventricular (LV) systolic function is very rare.

Patient Concerns: We experienced a representative case of a patient who presented with severe LV dysfunction related to thyroid storm and needed extracorporeal membrane oxygenation (ECMO) temporally.

Diagnosis: Thyrotoxic cardiomyopathy.

Interventions And Outcomes: Aggressive antithyroid therapy, including steroid pulse to hyperthyroidism, leads to the dramatic improvement of cardiac function and she was successfully weaned from ECMO.

Lessons: The most outstanding feature of the current case was the rapid decrease of cardiac injury and improvement of cardiac function by strengthening antithyroid therapy, including steroid pulse, without thyroid hormone level normalization. In thyroid storm, various systemic inflammatory reactions have different time courses and among them, the cardiac phenotype emerges in most striking and critical ways.
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http://dx.doi.org/10.1097/MD.0000000000007053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459733PMC
June 2017

Effects of Long-Acting Loop Diuretics in Heart Failure With Reduced Ejection Fraction Patients With Cardiac Resynchronization Therapy.

Int Heart J 2017 Apr 17;58(2):211-219. Epub 2017 Mar 17.

Division of Cardiology, Mitsui Memorial Hospital.

There have been no reports evaluating the impact of long-acting loop diuretics (LLD) on the outcome of heart failure (HF) and arrhythmia treatment in HF with reduced ejection fraction (HFrEF) patients implanted with a cardiac resynchronization therapy (CRT) device.This was a prospective, single-blind, randomized crossover study. We allocated 21 consecutive CRT implanted patients into 2 groups. The furosemide group received furosemide as a first treatment and azosemide as a second treatment. The azosemide group received this treatment in the reverse order. The first treatment was given to each group for 6 months and the second treatment continued for an additional 6 months. We combined the data of each medication regimen in each group and analyzed it at baseline, 6 months, and 1 year. The primary endpoints were the variation of fluid index and thoracic impedance measured by CRT at 6 months.The baseline characteristics were similar for both groups. The difference in the primary endpoints was not statistically significant between the 2 medication arms (fluid index: -29.6 ± 64.4 versus 16.2 ± 48.2; P = 0.22, thoracic impedance: -0.49 ± 17.8 versus 2.45 ± 12.5; P = 0.56). Likewise, the clinical outcome of HF and the CRT derived parameters in both arms were comparable.HFrEF patients taking LLD after CRT implantation might be comparable to those taking short-acting loop diuretics in the treatment of HF and HF-associated arrhythmias.
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http://dx.doi.org/10.1536/ihj.16-290DOI Listing
April 2017

Impact of stent type and prolonged dual antiplatelet therapy on long-term clinical outcomes in hemodialysis patients with coronary artery disease.

Cardiovasc Interv Ther 2018 Jan 30;33(1):84-94. Epub 2016 Nov 30.

Division of Cardiology, Mitsui Memorial Hospital, 1 Kanda-Izumi-cho, Chiyoda-ku, Tokyo, 101-8643, Japan.

The aim of this study was to address 7-year clinical outcomes and impact of prolonged dual antiplatelet therapy (DAPT) after coronary stenting in hemodialysis patients. Our study included 123 consecutive hemodialysis patients who had undergone percutaneous coronary intervention with a drug-eluting stent (DES) or bare-metal stent (BMS) (DES: 64, BMS: 59) in our institution. We compared long-term clinical outcomes following DES with BMS implantation as well as clinical outcomes in patients on DAPT for ≥1 year (DAPT on group, 89) with those on DAPT for <1 year (DAPT off group, 34). We evaluated bleeding events and major adverse cardiac events (MACE), including cardiac death, non-fatal myocardial infarction, target vessel revascularization, and stent thrombosis. At 1 year after stenting, the incidence of MACE was significantly lower in the DES group than in the BMS group (DES versus BMS: 33.2 versus 51.8%; p = 0.045). However, this advantage of DES disappeared by the 7th year (DES versus BMS: 66.0 versus 70.0%; p = 0.42). The cumulative incidence of MACE beyond 1 year was significantly higher in the DAPT on group than in the DAPT off group (DAPT on versus DAPT off: 51.3 versus 18.5%; p = 0.047). The bleeding events in the DAPT on group were 5.1 times greater than in the DAPT off group (DAPT on versus DAPT off: 16.4 versus 3.2%; p = 0.06). Use of DES and prolonged DAPT did not improve 7-year clinical outcomes in hemodialysis patients with coronary artery disease.
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http://dx.doi.org/10.1007/s12928-016-0447-4DOI Listing
January 2018

In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche.

Nature 2011 Jun 8;474(7350):216-9. Epub 2011 Jun 8.

Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.

Stem cells reside in a specialized regulatory microenvironment or niche, where they receive appropriate support for maintaining self-renewal and multi-lineage differentiation capacity. The niche may also protect stem cells from environmental insults including cytotoxic chemotherapy and perhaps pathogenic immunity. The testis, hair follicle and placenta are all sites of residence for stem cells and are immune-suppressive environments, called immune-privileged sites, where multiple mechanisms cooperate to prevent immune attack, even enabling prolonged survival of foreign allografts without immunosuppression. We sought to determine if somatic stem-cell niches more broadly are immune-privileged sites by examining the haematopoietic stem/progenitor cell (HSPC) niche in the bone marrow, a site where immune reactivity exists. We observed persistence of HSPCs from allogeneic donor mice (allo-HSPCs) in non-irradiated recipient mice for 30 days without immunosuppression with the same survival frequency compared to syngeneic HSPCs. These HSPCs were lost after the depletion of FoxP3 regulatory T (T(reg)) cells. High-resolution in vivo imaging over time demonstrated marked co-localization of HSPCs with T(reg) cells that accumulated on the endosteal surface in the calvarial and trabecular bone marrow. T(reg) cells seem to participate in creating a localized zone where HSPCs reside and where T(reg) cells are necessary for allo-HSPC persistence. In addition to processes supporting stem-cell function, the niche will provide a relative sanctuary from immune attack.
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http://dx.doi.org/10.1038/nature10160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725645PMC
June 2011

[Measurement and evaluation of home blood pressure monitoring with particular emphasis on evaluating anti-hypertensive effects using a home blood pressure distribution diagram].

Nihon Jinzo Gakkai Shi 2006 ;48(4):354-64

Division of Internal Medicine, Sendai Shakaihoken Hospital, Japan.

Tight blood pressure control over a long period is important to prevent end-organ damage to the brain, heart, and kidneys, and to avoid the complications of hypertension. Control requires an accurate evaluation of treatment through an appropriate monitoring of home blood pressure. In this study, we evaluated a method of home blood pressure monitoring, in which we propose a home blood pressure distribution diagram to evaluate the effectiveness of anti-hypertensive therapy. 1 ) In home blood pressure measurements, the first reading was high, while the second and third readings were essentially similar and thus stable. 2 ) Home blood pressure showed great daily variations, thus necessitating the use of the mean blood pressure over a fixed period, and not the individual blood pressure readings. The mean (morning, mid-day, and evening) over a one-week period was unstable, while the readings were stable over a three-week period. 3 ) The diagrams showing the distribution of home blood pressure measurements obtained in the morning and at night over a long period allowed the degree of early morning hypertension and the effectiveness of long-term blood pressure control to be assessed, and thus were useful for selecting anti-hypertensive agents. 4 ) In elderly patients, a mid-day systolic pressure of 100 mmHg or less (particularly 90 mmHg or less) resulted in the onset of symptoms of excessive hypotensive effects, such as lightheadedness and fainting, which affected ADL and QOL. 5 ) Because of great daily variations, it is difficult to achieve the blood pressure target of 130/80 mmHg or less in patients with hypertension associated with diabetes mellitus or renal insufficiency. 6 ) The home blood pressure distribution diagram facilitated an understanding of the status of anti-hypertensive therapy by patients, and was useful for motivating patients to continue treatment.
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July 2006
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