Durability of thermal pulmonary vein isolation in persistent atrial fibrillation assessed by mandated repeat invasive study.

Background: No study has assessed the durability of pulmonary vein isolation (PVI) with radiofrequency (RF) and cryoballoon (CB) in patients with persistent atrial fibrillation. These data are especially lacking for those with significantly diseased left atria (LA).

Objectives: The goals of this study were to assess PVI durability in patients with significant LA disease and to compare reconnection rates between RF and CB.

Cryoballoon pulmonary vein isolation as first-line treatment of typical atrial flutter: long-term outcomes of the CRAFT trial.

Background: CRAFT was an international, multicentre, randomised controlled trial across 11 sites in the United UK and Switzerland. Given the evidence that pulmonary vein triggers may be responsible for atrial flutter (AFL) as well as atrial fibrillation (AF), we hypothesised that cryoballoon pulmonary vein isolation (PVI) would provide greater symptomatic arrhythmia reduction than cavotricuspid isthmus (CTI) ablation, whilst also reducing the subsequent burden of AF. Twelve-month outcomes were previously reported.

Cryoballoon Pulmonary Vein Isolation as First-Line Treatment for Typical Atrial Flutter.

Objective: We aimed to compare cryoballoon pulmonary vein isolation (PVI) with standard radiofrequency cavotricuspid isthmus (CTI) ablation as first-line treatment for typical atrial flutter (AFL).

Methods: Cryoballoon Pulmonary Vein Isolation as First-Line Treatment for Typical Atrial Flutter was an international, multicentre, open with blinded assessment trial. Patients with CTI-dependent AFL and no documented atrial fibrillation (AF) were randomised to either cryoballoon PVI alone or radiofrequency CTI ablation.

The anti-inflammatory effects of cannabidiol and cannabigerol alone, and in combination.

Introduction/background And Purpose: Studies with Cannabis Sativa plant extracts and endogenous agonists of cannabinoid receptors have demonstrated anti-inflammatory, bronchodilator, and antitussive properties in the airways of allergic and non-allergic animals. However, the potential therapeutic use of cannabis and cannabinoids for the treatment of respiratory diseases has not been widely investigated, in part because of local irritation of airways by needing to smoke the cannabis, poor bioavailability when administered orally due to the lipophilic nature of cannabinoids, and the psychoactive effects of Δ9-Tetrahydrocannabinol (Δ9-THC) found in cannabis. The primary purpose of this study was to investigate the anti-inflammatory effects of two of the non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG) alone and in combination, in a model of pulmonary inflammation induced by bacterial lipopolysaccharide (LPS).

An Analysis of Over-the-Counter Cannabidiol Products in the United Kingdom.

Over-the-counter cannabidiol (CBD) products have seen unprecedented recent growth in the United Kingdom. However, analysis of these predominantly unregulated products from other countries tells us that they are often mislabeled or contain unlabeled and potentially dangerous chemicals. Thus, the aim of the present study was to analyze CBD oils available in the United Kingdom.

Cryoballoon pulmonary vein isolation as first line treatment for typical atrial flutter (CRAFT): study protocol for a randomised controlled trial.

Purpose: Treatment of typical atrial flutter (AFL) with cavo-tricuspid isthmus (CTI) ablation is associated with a high occurrence rate of new onset atrial fibrillation (AF) during follow-up. There are data to support the addition of pulmonary vein isolation (PVI) to CTI ablation in patients with both AF and AFL, but the role of cryoballoon PVI only, with no CTI ablation, in AFL patients with no prior documentation of AF has not been studied.

Methods: CRAFT is an international, prospective, randomised, open with blinded assessment, multicentre superiority study comparing radiofrequency CTI ablation and cryoballoon PVI in patients with typical AFL.

Enhancing titres of therapeutic viral vectors using the transgene repression in vector production (TRiP) system.

A key challenge in the field of therapeutic viral vector/vaccine manufacturing is maximizing production. For most vector platforms, the 'benchmark' vector titres are achieved with inert reporter genes. However, expression of therapeutic transgenes can often adversely affect vector titres due to biological effects on cell metabolism and/or on the vector virion itself.

Nanoparticulate paclitaxel demonstrates antitumor activity in PC3 and Ace-1 aggressive prostate cancer cell lines.

Background: Paclitaxel is an effective antimitotic agent in cancer treatment; however, one of its most common toxicities is hypersensitivity due to excipients used for water solubility. Nanoparticulate paclitaxel (Crititax®, CTI52010) is paclitaxel that consists only of nanoparticulate drug in saline. Our objective was to examine the effect of nanoparticulate paclitaxel on prostate cancer cells derived from castration-resistant prostate cancer in men and dogs, as companion dogs represent a unique naturally occurring model of castration-resistant prostate cancer.

High-throughput screening of a diversity collection using biodefense category A and B priority pathogens.

One of the objectives of the National Institutes of Allergy and Infectious Diseases (NIAID) Biodefense Program is to identify or develop broad-spectrum antimicrobials for use against bioterrorism pathogens and emerging infectious agents. As a part of that program, our institution has screened the 10 000-compound MyriaScreen Diversity Collection of high-purity druglike compounds against three NIAID category A and one category B priority pathogens in an effort to identify potential compound classes for further drug development. The effective use of a Clinical and Laboratory Standards Institute-based high-throughput screening (HTS) 96-well-based format allowed for the identification of 49 compounds that had in vitro activity against all four pathogens with minimum inhibitory concentration values of ≤16 µg/mL.

Inhibition and activation by CD244 depends on CD2 and phospholipase C-gamma1.

Regulation by the NK and T cell surface receptor CD244 in mice and humans depends both on engagement at the cell surface by CD48 and intracellular interactions with SAP and EAT-2. Relevance to human disease by manipulating CD244 in mouse models is complicated by rodent CD2 also binding CD48. We distinguish between contributions of mouse CD244 and CD2 on engagement of CD48 in a mouse T cell hybridoma.

Direct and indirect interactions of the cytoplasmic region of CD244 (2B4) in mice and humans with FYN kinase.

Engagement of the receptor CD244 (2B4) by its ligand CD48 has inhibitory and activating potential, and this differs depending on experimental systems in mouse and human. We show that, in both mouse and human upon engagement of its ligand CD48, CD244 can give a negative signal to natural killer cells, implying conservation of function between the two species. The signaling mechanisms used by CD244 in both human and mouse are conserved as shown by quantitative analyses of the direct molecular interactions of the SH2 domains of the adaptors SLAM-associated protein (SAP) and EAT-2 and of FYN kinase with CD244 together with the indirect interactions of the FYN SH2 domain with EAT-2.

CD6 regulates T-cell responses through activation-dependent recruitment of the positive regulator SLP-76.

Deciphering the role of lymphocyte membrane proteins depends on dissecting the role of a protein in the steady state and on engagement with its ligand. We show that expression of CD6 in T cells limits their responsiveness but that engagement by the physiological ligand CD166 gives costimulation. This costimulatory effect of CD6 is mediated through phosphorylation-dependent binding of a specific tyrosine residue, 662Y, in its cytoplasmic region to the adaptor SLP-76.

Linking the T cell surface protein CD2 to the actin-capping protein CAPZ via CMS and CIN85.

Recruitment of CD2 to the immunological synapse in response to antigen is dependent on its proline-rich cytoplasmic tail. A peptide from this region (CD2:322-339) isolated CMS (human CD2AP); a related protein, CIN85; and the actin capping protein, CAPZ from a T cell line. In BIAcore analyses, the N-terminal SH3 domains of CMS and CIN85 bound CD2:322-339 with similar dissociation constants (KD = approximately 100 microm).

Diatom motility: the search for independent replication of biological effects of extremely low-frequency electromagnetic fields.

Purpose: To investigate the hypothesis that exposure to a certain combination of static and time-varying electromagnetic fields (EMF) results in an increase in motility of the marine diatom Amphora coffeaeformis.

Materials And Methods: Diatom motility on agar was positively correlated with calcium ion (Ca2+) concentration. In previous experiments extremely low frequency EMF (16 Hz) had the greatest effect on diatoms at suboptimal for movement Ca2+ concentrations.

Diatom motility and low frequency electromagnetic fields--a new technique in the search for independent replication of results.

The hypothesis that exposure to a certain combination of static and alternating electromagnetic fields (EMFs) results in an increase in motility of the marine diatom Amphora coffeaeformis was tested. Diatom motility in three strains of A. coffeaeformis was positively correlated with extracellular calcium ion (Ca2+) concentration.

Characterization of the echovirus 7 receptor: domains of CD55 critical for virus binding.

CD55, or decay-accelerating factor (DAF), is a cell surface glycoprotein which regulates complement activity by accelerating the decay of C3/C5 convertases. Recently, we and others have established that this molecule acts as a cellular receptor for echovirus 7 and related viruses. DAF consists of five domains: four short consensus repeats (SCRs) and a serine/threonine-rich region, attached to the cell surface by a glycosylphosphatidyl inositol anchor.

Decay-accelerating factor CD55 is identified as the receptor for echovirus 7 using CELICS, a rapid immuno-focal cloning method.

Using an anti-receptor mAb that blocks the attachment of echovirus 7 and related viruses (echoviruses 13, 21, 29 and 33), we have isolated a complementary DNA clone that encodes the human decay-accelerating factor (CD55). Mouse cells transfected with the CD55 clone bind echovirus 7, and this binding is blocked by the anti-receptor mAb. The method used (CELICS) allows rapid and direct cloning of genes encoding cell surface receptors.