Hiroko Beck

Glia Induce Dendritic Growth in Cultured Sympathetic Neurons by Modulating the Balance between Bone Morphogenetic Proteins (BMPs) and BMP Antagonists

Dendritic growth in cultured sympathetic neurons requires specific trophic interactions. Previous studies have demonstrated that either coculture with glia or exposure to recombinant bone morphogenetic proteins (BMPs) is both necessary and sufficient to induce dendrite formation. These observations led us to test the hypothesis that BMPs mediate glial-induced dendritic growth. In situhybridization and immunocytochemical studies indicate that the spatiotemporal expression of BMP5, -6, and -7 in rat superior cervical ganglia (SCG) is consistent with their proposed role in dendritogenesis. In vitro, both SCG glia and neurons were found to express BMP mRNA and protein when grown in the presence or absence of the other cell type. However, addition of ganglionic glia to cultured sympathetic neurons causes a marked increase in BMP proteins coincident with a significant decrease in follistatin and noggin. Functional assays indicate that glial-induced dendritic growth is significantly reduced by BMP7 antibodies and completely inhibited by exogenous noggin and follistatin. These data suggest that glia influence the rapid perinatal expansion of the dendritic arbor in sympathetic neurons by increasing BMP activity via modulation of the balance between BMPs and their antagonists.

Bone morphogenetic protein-5 (BMP-5) promotes dendritic growth in cultured sympathetic neurons

BackgroundBMP-5 is expressed in the nervous system throughout development and into adulthood. However its effects on neural tissues are not well defined. BMP-5 is a member of the 60A subgroup of BMPs, other members of which have been shown to stimulate dendritic growth in central and peripheral neurons. We therefore examined the possibility that BMP-5 similarly enhances dendritic growth in cultured sympathetic neurons.ResultsSympathetic neurons cultured in the absence of serum or glial cells do not form dendrites; however, addition of BMP-5 causes these neurons to extend multiple dendritic processes, which is preceded by an increase in phosphorylation of the Smad-1 transcription factor. The dendrite-promoting activity of BMP-5 is significantly inhibited by the BMP antagonists noggin and follistatin and by a BMPR-IA-Fc chimeric protein. RT-PCR and immunocytochemical analyses indicate that BMP-5 mRNA and protein are expressed in the superior cervical ganglia (SCG) during times of initial growth and rapid expansion of the dendritic arbor.ConclusionsThese data suggest a role for BMP-5 in regulating dendritic growth in sympathetic neurons. The signaling pathway that mediates the dendrite-promoting activity of BMP-5 may involve binding to BMPR-IA and activation of Smad-1, and relative levels of BMP antagonists such as noggin and follistatin may modulate BMP-5 signaling. Since BMP-5 is expressed at relatively high levels not only in the developing but also the adult nervous system, these findings suggest the possibility that BMP-5 regulates dendritic morphology not only in the developing, but also the adult nervous system.

Cerebrospinal fluid contains biologically active bone morphogenetic protein-7.

Bone morphogenetic proteins (BMPs) regulate the development and function of many types of neurons. However, little is known of the actual concentrations of BMPs in the various parts of the brain. In this study, we considered the possibility that BMPs might be present in cerebrospinal fluid (CSF). Western blot analysis of normal adult bovine CSF revealed the presence of dimeric and monomeric forms of BMP-7, and the concentration of this molecule was found to be approximately 12 ng/ml in a radioimmunoassay. Since BMP-7 is known to induce dendritic growth in rat sympathetic neurons, this was used as a bioassay to examine the biological activity of the BMP-7 present in CSF. Addition of normal bovine CSF to cultures of sympathetic neurons produced a dose-dependent increase in dendritic growth and the magnitude of this response approximated that obtained with maximally effective concentrations of exogenous BMP-7. Moreover, CSF-induced dendritic growth was inhibited by follistatin, a protein that can sequester BMPs, and by either of two monoclonal antibodies that react with BMP-7. These results show that, unlike most other neurotrophic factors, BMP-7 is a constituent of normal CSF and is present at concentrations sufficient to elicit a near maximal biological response.

Acute Management of Atrial Fibrillation : From Emergency Department to Cardiac Care Unit

Atrial fibrillation (AF) is the most common tachyarrhythmia encountered in clinical practice. One-third of hospitalizations in the United States are attributed to AF, with increasing rates in the past decade. Significant morbidity and mortality, including ∼15% to 20% of all ischemic strokes, result from AF. AF is associated with many causes and comorbidities. Hallmarks of acute AF management are accurate diagnosis, clinical stabilization, symptom relief through rate or rhythm control, thromboembolic stroke risk modification, and treatment of underlying causes. Meticulous and individualized acute evaluation based on these goals facilitates successful transition to long-term collaborative optimization of outcomes.

Absence of Cardiovascular Implantable Electronic Device Infection in Remote Implantations Demonstrated by Fluorine-18 Positron Emission Tomography

We read with strong interest the paper by Sarrazin et al. ([1][1]), which reported on the utility of Fluorine-18 (18F-FDG) positron emission tomography (PET)/computed tomography (CT) for identification of cardiovascular implantable electronic device (CIED) infections. As noted in the article, the

Right Ventricular Versus Biventricular Pacing for Heart Failure and Atrioventricular Block.

The use of cardiac resynchronization therapy (CRT) is well accepted as an important option for the treatment of patients with systolic heart failure and prolonged QRS duration. CRT for patients with narrow QRS complexes is reserved for patients who are undergoing implantation of new or replacement pacemakers or implantable cardioverter defibrillators with an anticipated significant requirement for ventricular pacing. The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) Trial examined the role of CRT in heart failure patients with atrioventricular block and demonstrated significantly better outcomes with CRT compared to right ventricular pacing. On the other hand, conflicting preliminary data were reported by the Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace) Trial investigators. In this review, we will discuss the adverse consequences of chronic right ventricular pacing, the options of alternate pacing sites in the right ventricle versus biventricular pacing, and the findings from the BLOCK HF Trial as well as the preliminary data from the BioPace Trial. Our goal is to explore the role of biventricular pacing in patients with atrioventricular block.

The use of cardiac-CT alone to exclude left atrial thrombus before atrial fibrillation ablation: Efficiency, safety, and cost analysis

Atrial fibrillation (AF) is a growing financial burden on the healthcare system. Cardiac computed tomographic angiography (CCTA) is needed for pulmonary vein mapping before AF ablation (AFA). CCTA has shown to be an alternative to transesophageal echocardiogram (TEE) to rule out left atrial appendage thrombus (LAAT) pre‐AFA. We aim to examine the safety, cost‐effectiveness, and time‐efficiency of utilizing CCTA alone to rule out LAAT before AFA.

Validation of a smartphone‐based event recorder for arrhythmia detection

Ambulatory cardiac monitoring devices such as external loop recorders (ELRs) are often used in the outpatient clinic to evaluate palpitations. However, ELRs can be bulky and uncomfortable to use, especially in public, at work, or in social situations. An alternative approach is a smartphone‐based electrocardiographic (ECG) recorder/event recorder (Kardia Mobile [KM]), but the comparative diagnostic yield of each approach has not been studied.

Quality of life outcomes in transcatheter aortic valve replacement patients requiring pacemaker implantation

Permanent pacemaker implantation is the most common complication after Transcatheter aortic valve replacement (TAVR) and is associated with worse outcomes and mortality. However, its impact on quality‐of‐life (QoL) outcomes remains unknown.

IMPROVEMENT IN COST AND EFFICIENCY IN ELECTROPHYSIOLOGY LABORATORY BY CARDIAC COMPUTED TOMOGRAPHY TO EXCLUDE LEFT ATRIAL APPENDAGE THROMBUS PRIOR TO ATRIAL FIBRILLATION ABLATION

Background: Atrial fibrillation (AF) is an ever-increasing problem with growing financial burden on the healthcare system.