A5057915557- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Asthma and respiratory diseases
- Allergic Rhinitis and Sensitization
- Ion Channels and Receptors
- Calcium signaling and nucleotide metabolism
- Neuroscience and Neural Engineering
- Dermatology and Skin Diseases
- Receptor Mechanisms and Signaling
- Neuroscience of respiration and sleep
- Electrostatic Discharge in Electronics
- Heart Rate Variability and Autonomic Control
- Mast cells and histamine
- PARP inhibition in cancer therapy
- Neuroendocrine regulation and behavior
- Nicotinic Acetylcholine Receptors Study
- Cell Image Analysis Techniques
- Advanced biosensing and bioanalysis techniques
- Thermoregulation and physiological responses
- Model Reduction and Neural Networks
- Congenital heart defects research
- Muscle Physiology and Disorders
- Advanced Biosensing Techniques and Applications
- Error Correcting Code Techniques
- Blind Source Separation Techniques
University of Liverpool
2018-2023
University of Oxford
2014-2019
University of Bristol
2013
Imperial College London
1997-2001
National Institutes of Health
1998-2001
Lung Institute
1999-2000
King's College London
1999
Royal Brompton Hospital
1998
Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis, although it questionable whether there long-term benefit after the discontinuation of treatment.
Bronchiectasis is a chronic suppurative lung disease characterised by irreversible dilation of the bronchi and persistent purulent sputum. The immunopathology was studied using quantitative immunostaining technique with particular reference to T lymphocytes, macrophages, granulocytes.Bronchial mucosal biopsy specimens were obtained fibreoptic bronchoscopy from 12 patients bronchiectasis (six receiving inhaled steroids) 11 normal healthy controls. Immunostaining (APAAP method) performed on...
Allergic rhinitis is associated with specific histopathologic changes in the nasal mucosa including squamous metaplasia and local eosinophilia. Previous studies have shown that mometasone furoate aqueous spray effective well tolerated reducing perennial seasonal allergic symptoms. We undertook a multicenter, open‐label study to evaluate, by biopsy, tissue use (200 μg/day) during 12‐month treatment period patients rhinitis. Of 69 enrolled study, 52 completed all 12 months of treatment. Nasal...
Nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic ADP-ribose (cADPR) are Ca2+-mobilizing messengers important for modulating cardiac excitation–contraction coupling pathophysiology. CD38, which belongs to the ADP-ribosyl cyclase family, catalyzes synthesis of both NAADP cADPR in vitro. However, it remains unclear whether this is main enzyme their production under physiological conditions. Here we show that membrane fractions from WT but not CD38−/− mouse hearts supported...
Abstract Single-molecule research techniques such as patch-clamp electrophysiology deliver unique biological insight by capturing the movement of individual proteins in real time, unobscured whole-cell ensemble averaging. The critical first step analysis is event detection, so called “idealisation”, where noisy raw data are turned into discrete records protein movement. To date there have been practical limitations idealisation; high quality idealisation typically laborious and becomes...
The production of TH 2 ‐type cytokines [interleukin‐4 (IL‐4) and IL‐5] tissue eosinophilia are characteristic features allergic diseases. It was previously reported that at 24 h after allergen provocation, CD3 + T‐lymphocytes were the principal cell source IL‐4 IL‐5 mRNA transcripts in both atopic asthma rhinitis. To investigate whether expressed earlier during late nasal responses if so, which cell(s) responsible. Nasal biopsies obtained 6 challenge following a control with diluent....
Background: Allergen challenge in allergic rhinitis patients leads to local eosinophilia and Th2‐type cytokine expression. Natural exposure grass pollen is additionally characterized by epithelial mast‐cell infiltration. We hypothesized that perennial also associated with T‐cell eosinophil infiltration of the nasal mucosa, expression, increased numbers mast cells. Methods: Nasal biopsies from controls were analysed immunocytochemistry for different cell populations situ hybridization...
Grass pollen immunotherapy for the treatment of seasonal allergic rhinitis ('summer hayfever') results in improvement symptoms, a reduction early and late phase responses to allergen provocation decreased tissue eosinophilia. Immunotherapy may act by altering pattern cytokine production allergen-specific T cells from 'Th2-type' (IL-4 IL-5) profile 'Th1-type' (interferon-gamma (IFN-gamma)) profile. We set out determine whether clinical following specific is accompanied reduced...
SUMMARY Grass pollen immunotherapy for the treatment of seasonal allergic rhinitis (‘summer hayfever’) results in improvement symptoms, a reduction early and late phase responses to allergen provocation decreased tissue eosinophilia. Immunotherapy may act by altering pattern cytokine production allergen-specific T cells from ‘Th2-type’ (IL-4 IL-5) profile ‘Th1-type’ (interferon-gamma (IFN-γ)) profile. We set out determine whether clinical following specific is accompanied reduced...
Key points The role of trimeric intracellular cation (TRIC) channels is not known, although evidence suggests they may regulate ryanodine receptors (RyR) via multiple mechanisms. We therefore investigated whether Tric‐a gene knockout (KO) alters the single‐channel function skeletal RyR (RyR1). find that RyR1 from KO mice are more sensitive to inhibition by divalent cations, respond normally cytosolic Ca 2+ , ATP, caffeine and luminal . In presence Mg ATP cannot effectively activate mice....
There are two subtypes of trimeric intracellular cation (TRIC) channels but their distinct single-channel properties and physiological regulation have not been characterized. We examined the differences in function between native skeletal muscle sarcoplasmic reticulum (SR) K
The synovium secretes synovial fluid, but is also richly innervated with nociceptors and acts as a gateway between avascular joint tissues the circulatory system. Resident fibroblast-like synoviocytes' (FLS) calcium-activated potassium channels (KCa) change in activity arthritis models this correlates FLS activation.To investigate activation an vitro model of inflammatory arthritis; 72 h treatment cytokines TNFα IL1β.FLS cells were isolated from rat membranes. We analyzed global changes mRNA...
A fully integrated partial response maximum likelihood (PRML) read/write IC with analog adaptive equalization operates up to 200 MSample/s. The chip implements both matched spectral null (MSN) trellis and standard PR4 Viterbi detectors in the digital domain as well servo. device is a mature 0.7-/spl mu/m BiCMOS technology, has die size of 54 mm/sup 2/, dissipates 2 W MSN code or 1.5 at 4.5-V supply
<h2>Abstract</h2> Sarcoplasmic reticulum (SR) K<sup>+</sup> channels are voltage-regulated that thought to be actively gating when the membrane potential across SR is close zero as expected physiologically. A characteristic of they gate subconductance open states but relevance events and their contribution overall current flowing through at physiological potentials not known. We have investigated relationship between full conductance openings developed kinetic models describe voltage...
In humans, skin is a primary thermoregulatory organ, with vasodilation leading to rapid body cooling, whereas in Rodentia the tail performs an analogous function. Many thermodetection mechanisms are likely be involved including transient receptor potential vanilloid-type 4 (TRPV4), ion channel thermosensitive properties. Previous studies have shown that TRPV4 vasodilator by local action blood vessels, so here, we investigated whether constitutive activity affects Mus muscularis vascular tone...
Development of automated analysis tools for “single ion channel” recording is hampered by the lack available training data. For machine learning based tools, very large sets are necessary with sample-by-sample point labelled data (e.g., 1 sample every 100microsecond). In an experimental context, such human supervision, and whilst this feasible simple analysis, it infeasible to generate enormous datasets that would be a big approach using hand crafting. work we aimed develop methods simulated...
The paraventricular nucleus (PVN) of the hypothalamus is an important autonomic control centre in brain with roles stress, metabolism, cardiovascular function and homeostasis. Identified PVN neurones project directly to spinal cord can modulate via sympathetic control, however, underlying mechanisms are not fully understood. Work from our group has highlighted for TRPV4 osmosensing thermoregulation PVN. To investigate whether channels may play a role modulating function, we have used...
Abstract In humans the skin is a primary thermoregulatory organ, with vasodilation leading to rapid body cooling, whereas in Rodentia tail performs an analogous function. Many thermodetection mechanisms are likely be involved including transient receptor potential vanilloid-type 4 (TRPV4), widely distributed ion channel both mechanical and thermosensitive properties. Previous studies have shown that TRPV4 can act as vasodilator by local action blood vessels, this study, we investigated...