Publications by authors named "Flynn R"

The use of antithrombotic medicines in patients who have a history of intracerebral haemorrhage is widely perceived as being contraindicated. However, many patients with intracerebral haemorrhage may suffer from conditions for which antithrombotic medicines are indicated. Such scenarios represent a therapeutic dilemma whereby treating infers an increased risk of recurrent intracerebral haemorrhage, but not treating infers an increase of thrombotic complications.

View Article and Find Full Text PDF

Transmigration of neuropathogens across the blood-brain barrier is a key step in the development of central nervous system infections, making it a prime target for drug development. The ability of neuropathogens to traverse the blood-brain barrier continues to inspire researchers to understand the specific strategies and molecular mechanisms that allow them to enter the brain. The availability of models of the blood-brain barrier that closely mimic the situation in vivo offers unprecedented opportunities for the development of novel therapeutics.

View Article and Find Full Text PDF

Background: The most appropriate management of incidental prostate cancers diagnosed at transurethral resection of prostate has been debated. It is important to determine the long-term outcomes to establish an appropriate management in patients with incidental prostate cancer.

Aims: We aim to determine 10-year survival and to identify the factors of worse prognosis of incidental prostate cancers diagnosed at transurethral resection of prostate.

View Article and Find Full Text PDF

Objective: To investigate the changing pattern of antimicrobial resistance in Escherichia coli urinary tract infection over an eleven year period, and to determine whether E. coli antibiotic resistance rates vary depending on whether the UTI represents a nosocomial, community acquired or urology patient specific infection.

Patient And Methods: A retrospective analysis of the 42,033 E.

View Article and Find Full Text PDF

Background: Epstein-Barr virus (EBV) causes a range of life-threatening B-lymphocyte malignancies but, despite the use of various strategies, treatment remains problematic.

Methods: In the present study, we developed a non-integrating lentiviral vector (NILV) that mediates specific killing of EBV nuclear antigen 1 (EBNA1)-expressing cells with minimal toxicity to EBNA1-negative cells. The EBV family of repeats (FR) was cloned intok the NILV genome upstream of various transgenes.

View Article and Find Full Text PDF

Expression of atheroprotective genes in the blood vessel wall is potentially an effective means of preventing or reversing atherosclerosis. Development of this approach has been hampered by lack of a suitable gene-transfer vector. We used a helper-dependent adenoviral (HDAd) vector to test whether expression of apolipoprotein A-I (apoA-I) in the artery wall could retard the development of atherosclerosis in hyperlipidemic rabbits.

View Article and Find Full Text PDF

Background: Interleukin (IL)-25 (IL-17E) is a potent inducer of the type-2 immune effector response. Previously we have demonstrated that a neutralizing anti-IL-25 antibody, given during the establishment of ovalbumin-specific lung allergy, abrogates airways hyperreactivity.

Objective: Blocking IL-25 results in the suppression of IL-13, a cytokine known to exacerbate pulmonary inflammation, and an unexpected reciprocal increase in IL-17A.

View Article and Find Full Text PDF

Alternatively activated macrophages (AAM) are a key feature Th2 immunity and have been associated with a variety of roles during helminth infection. The role this cell subset plays in protozoan infection remain relatively unexplored, herein we describe the effects of a redox enzyme (rTgPrx) derived from Toxoplasma gondii on murine macrophage phenotype in vitro. RTgPrx has been previously associated with the maintainance of parasite oxidative balance.

View Article and Find Full Text PDF

Divergent transcription occurs at the majority of RNA polymerase II (RNAPII) promoters in mouse embryonic stem cells (mESCs), and this activity correlates with CpG islands. Here we report the characterization of upstream antisense transcription in regions encoding transcription start site associated RNAs (TSSa-RNAs) at four divergent CpG island promoters: Isg20l1, Tcea1, Txn1, and Sf3b1. We find that upstream antisense RNAs (uaRNAs) have distinct capped 5' termini and heterogeneous nonpolyadenylated 3' ends.

View Article and Find Full Text PDF

Room temperature spasing of surface plasmon polaritons at 1.46 μm wavelength has been demonstrated by sandwiching a gold-film plasmonic waveguide between optically pumped InGaAs quantum-well gain media. The spaser exhibits gain narrowing, the expected transverse-magnetic polarization, and mirror feedback provided by cleaved facets in a 1-mm long cavity fabricated with a flip-chip approach.

View Article and Find Full Text PDF

This study, for the first time, investigates and quantifies the influence of slight changes in solution pH and ionic strength (IS) on colloidal microsphere deposition site coverage by Suwannee River Humic Acid (SRHA) in a column matrix packed with saturated iron-oxide coated sand. Triple pulse experimental (TPE) results show adsorbed SRHA enhances microsphere mobility more at higher pH and lower IS and covers more sites than at higher IS and lower pH. Random sequential adsorption (RSA) modelling of experimental data suggests 1 μg of adsorbed SRHA occupied 9.

View Article and Find Full Text PDF

Follicular Th (T(FH)) cells are specialized in provision of help to B cells that is essential for promoting protective Ab responses. CD28/B7 (B7-1 and B7-2) interactions are required for germinal center (GC) formation, but it is not clear if they simply support activation of naive CD4 T cells during initiation of responses by dendritic cells or if they directly control T(FH) cells and/or directly influence follicular B cell differentiation. Using a model of vaccinia virus infection, we show that B7-2 but not B7-1 deficiency profoundly impaired T(FH) cell development but did not affect CD4 T cell priming and Th1 differentiation.

View Article and Find Full Text PDF

The genome is extensively transcribed into long intergenic noncoding RNAs (lincRNAs), many of which are implicated in gene silencing. Potential roles of lincRNAs in gene activation are much less understood. Development and homeostasis require coordinate regulation of neighbouring genes through a process termed locus control.

View Article and Find Full Text PDF

Maintenance of telomeres requires both DNA replication and telomere 'capping' by shelterin. These two processes use two single-stranded DNA (ssDNA)-binding proteins, replication protein A (RPA) and protection of telomeres 1 (POT1). Although RPA and POT1 each have a critical role at telomeres, how they function in concert is not clear.

View Article and Find Full Text PDF

Background: Current UK guidelines for the identification, management and referral of chronic kidney disease advise an early-morning urine sample for the albumin:creatinine ratio or the protein:creatinine ratio (PCR) in order to quantify proteinuria. Estimated protein output (EPO) is an alternative and possibly better method of quantifying proteinuria which takes lean weight into consideration.

Methods: We carried out a single-centre study of 36 adult patients with proteinuric nephropathy over a period of 18 months.

View Article and Find Full Text PDF

Induction of CD8+ T cell immunity is a key characteristic of an effective vaccine. For safety reasons, human vaccination strategies largely use attenuated nonreplicating or weakly replicating poxvirus-based vectors, but these often elicit poor CD8+ T cell immunity and might not result in optimal protection. Recent studies have suggested that virulence is directly linked to immunogenicity, but the molecular mechanisms underlying optimal CD8+ T cell responses remain to be defined.

View Article and Find Full Text PDF

The success of gene therapy hinges on achievement of adequate transgene expression. To ensure high transgene expression, many gene-therapy vectors include highly active virus-derived transcriptional elements. Other vectors include tissue-specific eukaryotic transcriptional elements, intended to limit transgene expression to specific cell types, avoid toxicity and prevent immune responses.

View Article and Find Full Text PDF

Cell-fate transitions involve the integration of genomic information encoded by regulatory elements, such as enhancers, with the cellular environment. However, identification of genomic sequences that control human embryonic development represents a formidable challenge. Here we show that in human embryonic stem cells (hESCs), unique chromatin signatures identify two distinct classes of genomic elements, both of which are marked by the presence of chromatin regulators p300 and BRG1, monomethylation of histone H3 at lysine 4 (H3K4me1), and low nucleosomal density.

View Article and Find Full Text PDF

The RGK family of proteins, small GTPases of the Ras superfamily, are known to regulate calcium currents. It is commonly thought that this is due to an interaction with the Cavβ subunit, however, the mechanism of this inhibition is unclear. There have been conflicting reports of whether RGK proteins can affect channel trafficking or whether they reduce calcium currents by interacting with channels at the membrane.

View Article and Find Full Text PDF

Background And Purpose: Antiplatelet medicines are commonly perceived as contraindicated after intracerebral hemorrhage (ICH). Many ICH patients have or will have indications for antiplatelet therapy. This observational study describes the level of antiplatelet prescribing and rate of subsequent events after ICH in Tayside, Scotland.

View Article and Find Full Text PDF

The integrity of the genome is constantly challenged by intrinsic and extrinsic genotoxic stresses that damage DNA. The cellular responses to DNA damage are orchestrated by DNA damage signaling pathways, also known as DNA damage checkpoints. These signaling pathways play crucial roles in detecting DNA damage, regulating DNA repair and coordinating DNA repair with other cellular processes.

View Article and Find Full Text PDF

Objectives: To examine the success rate of electroejaculatory stimulation in patients with acquired spinal injuries in a single Irish institution. The use of electroejaculatory stimulation is of benefit in patients with spinal cord injury who wish to have children.

Methods: A retrospective review of the Hospital In-Patient Enquiry scheme database and the patients' medical notes was performed.

View Article and Find Full Text PDF