Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in Dextran Sulfate Sodium-Induced Murine Model of Ulcerative Colitis.

Oxidative stress is implicated in the pathogenesis of various acute disorders including ischemia/reperfusion injury, ultraviolet/radiation burn, as well as chronic disorders such as dyslipidemia, atherosclerosis, diabetes mellitus, chronic renal disease, and inflammatory bowel disease (IBD). However, the precise mechanism involved remains to be clarified. We formerly identified a novel apoptosis-inducing humoral protein, in a hypoxia/reoxygenation-conditioned medium of cardiac myocytes, which proved to be 69th tyrosine-sulfated eukaryotic translation initiation factor 5A (eIF5A).

Oxidative stress-responsive apoptosis inducing protein (ORAIP) plays a critical role in doxorubicin-induced apoptosis in rat cardiac myocytes.

Background: Oxidative stress is implicated in the pathogenesis of doxorubicin-induced apoptosis in cardiac myocytes. However, the precise mechanism remains uncertain. We identified an apoptosis-inducing humoral factor, in a conditioned medium from cardiac myocytes subjected to hypoxia/reoxygenation, to be 69th tyrosine-sulfated eukaryotic translation initiation factor 5A (eIF5A).

Oxidative stress-responsive apoptosis-inducing protein in patients with heterozygous familial hypercholesterolemia.

Oxidative stress, an inducer of apoptosis, plays a critical role in ischemia/reperfusion injury and atherosclerosis. We previously identified an apoptosis-inducing ligand, the post-translationally modified secreted form of eukaryotic translation initiation factor 5A (eIF5A), 'oxidative stress-responsive apoptosis-inducing protein' (ORAIP). In this study, we investigated the role of ORAIP in patients with heterozygous familial hypercholesterolemia (HeFH), a leading cause of premature cardiovascular disease.

Oxidative stress-responsive apoptosis inducing protein (ORAIP) plays a critical role in cerebral ischemia/reperfusion injury.

Oxidative stress is known to play a critical role in the pathogenesis of various disorders, especially in ischemia/reperfusion (I/R) injury. We identified an apoptosis-inducing humoral factor and named this novel post translationally modified secreted form of eukaryotic translation initiation factor 5A (eIF5A) "oxidative stress-responsive apoptosis inducing protein" (ORAIP). The purpose of this study was to investigate the role of ORAIP in the mechanisms of cerebral I/R injury.

Elevation of the vitreous body concentrations of oxidative stress-responsive apoptosis-inducing protein (ORAIP) in proliferative diabetic retinopathy.

Purpose: Oxidative stress has been implicated in the pathogenesis of various disorders, including diabetic retinopathy (DR). Oxidative stress-responsive apoptosis-inducing protein (ORAIP; a tyrosine-sulfated secreted form of eukaryotic translation initiation factor 5A [eIF5A]) is a recently discovered pro-apoptotic ligand that is secreted from cells in response to oxidative stress and induces apoptosis in an autocrine fashion. This study aimed to determine if ORAIP plays a role in DR.

Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells.

We previously identified a novel apoptosis-inducing humoral factor in the conditioned medium of hypoxic/reoxygenated-cardiac myocytes. We named this novel post-translationally-modified secreted-form of eukaryotic translation initiation factor 5A Oxidative stress-Responsive Apoptosis-Inducing Protein (ORAIP). We confirmed that myocardial ischemia/reperfusion markedly increased plasma ORAIP levels and rat myocardial ischemia/reperfusion injury was clearly suppressed by neutralizing anti-ORAIP monoclonal antibodies (mAbs) in vivo.

Plasma levels of oxidative stress-responsive apoptosis inducing protein (ORAIP) in rats subjected to physicochemical oxidative stresses.

Oxidative stress is known to play a pivotal role in the pathogenesis of various disorders including atherosclerosis, aging and especially ischaemia/reperfusion injury. It causes cell damage that leads to apoptosis. However, the precise mechanism has been uncertain.

A Case of Takayasu's Arteritis with Total Occlusion of the Abdominal Aorta Treated Only with Oral Medication for More Than 40 Years.

Takayasu's arteritis affects most commonly young women, often causing stenotic and occasionally dilated lesions of the medium-to-large-sized arteries with an acute inflammatory signs and symptoms. Here, we report a rare case of Takayasu's arteritis with total occlusion of the abdominal aorta, which was successfully treated with medication alone and asymptomatic over 40 years. Magnetic resonance imaging revealed total occlusion of the abdominal aorta and stenosis of the right carotid artery.

Basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline.

We have recently demonstrated that basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias that have been induced by electrical stimulation of the cervical vagus. This study investigated whether similar basal cardiomyopathy would develop in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline. Adrenaline was intravenously infused for 10-360 seconds in anesthetized rabbits.

[An elderly woman with macrocytic anemia and acute high-output heart failure following acute bleeding due to a gastric ulcer].

Although macrocytic anemia can develop in patients with acute blood loss, such anemia in very old patients is uncommon. In this report, we describe the course of an 89-year-old woman who had a rapid recovery from macrocytic anemia by medication only after acute blood loss due to a gastric ulcer. She had been treated with antihypertensive drugs for the previous 28 years at our outpatient clinic, and was admitted because of acute anemia 6 days after she had experienced tarry stool.

Ventricular tachyarrhythmia-related basal cardiomyopathy in rabbits with vagal stimulation--a novel experimental model for inverted Takotsubo-like cardiomyopathy.

Background: Electrical stimulation of the intact (unsectioned) cervical vagus in rabbits frequently provokes ventricular tachyarrhythmias that are often accompanied by mitral regurgitation. Unique pathological lesions often arise on the mitral valve, papillary muscles, and mitral annulus (mitral complex), the latter two of which become swollen and stiffened. These lesions are reversible in nature.

A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity.

A conundrum of innate antiviral immunity is how nucleic acid-sensing Toll-like receptors (TLRs) and RIG-I/MDA5 receptors cooperate during virus infection. The conventional wisdom has been that the activation of these receptor pathways evokes type I IFN (IFN) responses. Here, we provide evidence for a critical role of a Toll-like receptor 3 (TLR3)-dependent type II IFN signaling pathway in antiviral innate immune response against Coxsackievirus group B serotype 3 (CVB3), a member of the positive-stranded RNA virus family picornaviridae and most prevalent virus associated with chronic dilated cardiomyopathy.

A case of neonatal lupus erythematosus presenting delayed dilated cardiomyopathy with circulating autoantibody to annexin A6.

Patients with neonatal lupus erythematosus (NLE) often have congenital heart block with or without heart failure and are born to mothers who have anti-SS-A and/or anti-SS-B antibodies. NLE has been considered to result from the placental transmission of maternal autoantibodies into the fetal circulation causing myocardial damage. We report a case of NLE with congenital heart block who had undergone pacemaker implantation at the age of 17, and then developed dilated cardiomyopathy (DCM) at the age of 19, which is much later than in most other cases.

Roles of programmed death-1 (PD-1)/PD-1 ligands pathway in the development of murine acute myocarditis caused by coxsackievirus B3.

Objective: This study was designed to investigate the roles of programmed death-1 (PD-1) and PD-1 ligands (PD-L) in the development of murine acute myocarditis caused by Coxsackievirus B3. PD-1/PD-L belong to the CD28/B7 superfamily, and the PD-1/PD-L pathway is known to transduce a negative immunoregulatory signal that antagonizes the T-cell receptor-CD28 signal and inhibits T-cell activation.

Methods: We first analyzed the expression of PD-L1/PD-L2 on cardiac myocytes in vivo and in vitro.

Gamma-delta T-cell-mediated dilated cardiomyopathy.

Gamma-delta T-cells are usually minor component of peripheral blood and lymphoid tissues, but may play an important role in autoimmune diseases. We here describe the first case of dilated cardiomyopathy (DCM) with heart infiltration by mostly gamma-delta T-cells, who improved significantly by steroid therapy. In general, steroid therapy has only a little effect on DCM, however these findings might have implications with respect to the selection of patients who might respond to immunosuppressive therapy.

Giant cell and Takayasu arteritis.

Purpose Of Review: Giant cell arteritis and Takayasu arteritis are well known large vessel vasculitides with an unknown etiology. As they have similar clinical features, this short article reviews recent advances in clinical and pathophysiological findings, focusing in particular on papers published in the past year.

Recent Findings: Delayed gadolinium-enhanced magnetic resonance imaging showed delayed hyperenhancement in the aortic wall in Takayasu arteritis.

Effect of the angiotensin II receptor blocker olmesartan on the development of murine acute myocarditis caused by coxsackievirus B3.

Ang II (Angiotensin II) has been shown to play a pivotal role in the pathophysiology of various organs, especially the cardiovascular system. The effects of ARBs (Ang II receptor blockers) in the treatment of hypertension, congestive heart failure and myocardial fibrosis have been analysed extensively in human trials, as well as animal models, and the focus of interest is now directed to its pleiotropic effects, especially on inflammatory disorders. To investigate the effects of a new ARB, olmesartan, on immune-mediated myocardial injury, the protective effects of olmesartan on the development of murine acute myocarditis caused by CVB3 (coxsackievirus B3) were analysed.

Takayasu myocarditis mediated by cytotoxic T lymphocytes.

A 15-year-old Japanese man was referred for evaluation of heart failure. Conventional heart failure therapy had little effect, and severe left ventricular dysfunction as well as elevated erythrocyte sedimentation rate persisted. Magnetic resonance angiography showed aortic dilatation with wall thickening characteristic of Takayasu's arteritis.

Hypoxia followed by reoxygenation induces secretion of cyclophilin A from cultured rat cardiac myocytes.

We previously reported that hypoxia followed by reoxygenation (hypoxia/reoxygenation) rapidly activated intracellular signaling such as mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated protein kinase (ERK) 1/2, p38MAPK, and stress-activated protein kinases (SAPKs). To investigate the humoral factors which mediate cardiac response to hypoxia/reoxygenation, we analyzed the conditioned media from cardiac myocytes subjected to hypoxia/reoxygenation by two-dimensional electrophoresis and mass spectrometry. We identified cyclophilin A (CyPA) as one of the proteins secreted from cardiac myocytes in response to hypoxia/reoxygenation.

Serum levels of endostatin, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in patients with acute myocardial infarction undergoing early reperfusion therapy.

Angiogenesis is controlled by anti-angiogenic factors as well as by angiogenic factors, such as VEGF (vascular endothelial growth factor) and HGF (hepatocyte growth factor). Endostatin, a potent endogenous angiogenesis inhibitor, is known to inhibit endothelial proliferation and suppress tumour growth. However, to date, little is known about the pathophysiology of endostatin in ischaemia/reperfusion.

Expression of costimulatory molecules (4-1BBL and Fas) and major histocompatibility class I chain-related A (MICA) in aortic tissue with Takayasu's arteritis.

To further investigate the immunological mechanisms involved, we analyzed the expression of costimulatory molecules in aortic tissue and their counterpart molecules on infiltrating cells of patients with Takayasu's arteritis. We also examined the expression of major histocompatibility complex (MHC) class I chain-related (MIC) A in aortic tissue, which is known to be induced by external stress, and its counterpart NKG2D receptors on infiltrating cells. Among these costimulatory molecules, strong expression of 4-1BBL and Fas was induced in the aortic tissue, and most of the infiltrating cells expressed 4-1BB and FasL, suggesting these pathways play critical roles in T-cell-mediated vascular injury.