Laura R Sadofsky

Laura R Sadofsky
University of Hull · Academic Cardiology

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44
Publications
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1,403
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Publications

Publications (44)
Article
Full-text available
Background Upper respiratory tract infections (URTIs) impact all age groups and have a significant economic and social burden on society, worldwide. Most URTIs are mild and self-limiting, but due to the wide range of possible causative agents, including Rhinovirus (hRV), Adenovirus, Respiratory Syncytial Virus (RSV), Coronavirus and Influenza, ther...
Article
Full-text available
Accurate and consistent assessments of cough are essential to advance the understanding of the mechanisms of cough and individualised the management of patients. Considerable progress has been made in this work. Here we reviewed the currently available tools for subjectively and objectively measuring both cough sensitivity and severity. We also pro...
Article
Full-text available
Chronic cough is the most common complaint in respiratory clinics. Most of them have identifiable causes and some may respond to common disease-modifying therapies. However, there are many patients whose cough lacks effective aetiologi-cally targeted treatments or remains unexplained after thorough assessments, which have been described as refracto...
Article
Full-text available
Human rhinovirus (RV) is the most common cause of upper respiratory tract infection (URTI) and chronic airway disease exacerbation. Cough is present in 50–80% of URTI cases, accompanied by heightened airway hypersensitivity, yet no effective treatment currently exists for this infectious cough. The mechanism by which RV causes cough and airway hype...
Article
Full-text available
Purpose There is currently no true macrophage cell line and in vitro experiments requiring these cells currently require mitogenic stimulation of a macrophage precursor cell line (THP-1) or ex vivo maturation of circulating primary monocytes. In this study, we characterise a human macrophage cell line, derived from THP-1 cells, and compare its phen...
Conference Paper
Rational and hypothesis: Human rhinovirus (HRV) infections are a major causative agent of upper respiratory tract infection (URTI) and are associated with acute exacerbations of asthma and COPD. URTI is associated with excessive production of mucus within the airway, particularly in sufferers of chronic respiratory conditions. This mucus may lead t...
Conference Paper
Introduction and objectives Oxygen is often used inappropriately in hospital for patients without significant systemic hypoxia. In lung disease correcting hypoxia has become a key treatment target. Here for the first time we explore the effect of oxygen on airway tone in human lung models. Methods Human lung specimens were obtained at resection fo...
Conference Paper
Introduction and objective URTI and chronic cough is estimated to cost the UK economy in excess of £1 billion annual however, the mechanism of cough hypersensitivity remains elusive. Neuromodulation provides a promising hypothesis whereby the purinoreceptor P2 × 3 on vagal afferent nerve fibres is activated through the release of extracellular ATP....
Article
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Chronic inflammatory diseases of the airways are associated with gastro-oesophageal reflux (GOR) and aspiration events. The observation of lipid-laden macrophages (LLMs) within the airway may indicate aspiration secondary to GOR. The proposed mechanism, that lipid droplets from undigested or partially digested food are aspirated leading to accumula...
Article
Previous studies showed the effects of resveratrol (RES) on several cancer cells, including prostate cancer (PCa) cell apoptosis without taking into consideration the impact of the tumor microenvironment (TME). The TME is composed of cancer cells, endothelial cells, blood cells and cancer-associated fibroblasts (CAF), the main source of growth fact...
Article
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Capsaicin, the hot component of chilli peppers, is a well-known tussive agent, which is regularly used as a tool to study cough and antitussives (1). Capsaicin is known to activate the transient receptor potential vanilloid 1 (TRPV1) cation channel which is thought to be involved in pain perception, inflammation, itch and cough (2-4). These functio...
Article
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In sarcoidosis, the proinflammatory cytokines interferon gamma, tumour necrosis factor and interleukin-6 are released by monocyte-derived macrophages and lymphocytes in the lungs and other affected tissues. Regulatory receptors expressed on monocytes and macrophages act to suppress cytokine production, and reduced expression of regulatory receptors...
Article
Background Sarcoidosis is characterised by release of pro-inflammatory cytokines in affected tissues. Lung macrophages, derived from blood monocytes, are potent producers of tumour necrosis factor (TNF) and interleukin-6 (IL-6) which contribute to the formation of sarcoid granulomata. Abnormalities of regulatory pathways that normally act to dampen...
Article
Aim of the study: Bleomycin-induced lung disease is a serious complication of therapy characterized by alveolar injury, cytokine release, inflammatory cell recruitment, and eventually pulmonary fibrosis. The mechanisms underlying bleomycin-induced pulmonary fibrosis may be relevant to other progressive scarring diseases of the lungs. Pulmonary vas...
Article
Aromatase inhibitors (AI) induce painful musculoskeletal symptoms (AIMSS), which are dependent upon the pain transducing receptor TRPA1. However, since the AI concentrations required to engage TRPA1 in mice are higher than those found in the plasma of patients, we hypothesized that additional factors may cooperate to induce AIMSS. Here we report th...
Article
Full-text available
Cough is a protective reflex to prevent aspiration and can be triggered by a multitude of stimuli. The commonest form of cough is caused by upper respiratory tract infection and has no benefit to the host. The virus hijacks this natural defence mechanism in order to propagate itself through the population. Despite the resolution of the majority of...
Article
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Multiple missense variants of TRPA1 and TRPM8 are recorded in the human genome single nucleotide polymorphism (SNP) database but their potential impact on channel signalling in patho-physiology is not fully explored. Variants, mostly quite rare in the general human population, alter sites in different structural domains of these homo-tetrameric ion...
Article
Sarcoidosis is a multi-system granulomatous disease characterised by increased tissue levels of Th1-like cytokines such as IFN-γ and TNF-α. Diminished immune responses have been reported in peripheral blood, yet the reasons for the difference between local and peripheral immunity are not understood. The aim of this study was to investigate whole bl...
Article
ABSTRACT Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown etiology, for which there is no curative pharmacological therapy. Bleomycin, an anti-neoplastic agent that causes lung fibrosis in human patients has been used extensively in rodent models to mimic IPF. In this review, we compare the pathogenesis and histological featu...
Conference Paper
Full-text available
Background Extensive research has realised the clinical benefits of endothelin antagonists in the treatment of pulmonary arterial hypertension of various aetiologies. A number of in vitro animal studies (1-3) have shown that ET-1 is a more potent and more efficacious constrictor in the pulmonary veins than the pulmonary arteries which suggest that...
Article
Aims Demonstration of lipid-laden macrophages in respiratory secretions has been suggested to be a marker of reflux and aspiration. However studies looking at the diagnostic value of quantifying macrophage ingested lipids have been inconclusive. We wanted to look evaluate the utility of this technique in diagnosing airway reflux. Methods In this pr...
Article
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The authors wish to make the following corrections to this paper [1]: In Table 2 on page 623, the Quercinitol activation value for TRPA1V1 should be 2.3 instead of 57.6. Quercinitol does not activate TRPA1V1. We thank Michael J.M. Fisher (University of Erlangen, Germany) for his feedback which helped us to review our result. The authors would like...
Article
Full-text available
TRPM8 and TRPA1 are cold-temperature-sensitive nociceptors expressed in sensory neurons but their behaviour in neuronal cells is poorly understood. Therefore, DNA expression constructs containing human TRPM8 or TRPA1 cDNAs were transfected into HEK293 or SH-SY5Y neuroblastoma cells and G418 resistant clones analysed for effects of agonists and anta...
Article
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Transient receptor potential (TRP) ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are implicated in modulation of cough and nociception. In vivo, TRPA1 and TRPV1 are often co-expressed in neurons and TRPA1V1 hetero-tetramer formation is noted in cells co-transfected with the respective expression plasmids. In order to understand the impact of...
Article
Lung fibroblasts are involved in interstitial lung disease, chronic asthma, and chronic obstructive pulmonary disease (COPD). The expanded fibroblast population in airway disease leads to airway remodeling and contributes to the inflammatory process seen in these diseases. The cation channel transient receptor potential vanilloid-1 (TRPV1) is activ...
Article
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The California bay laurel or Umbellularia californica (Hook. & Arn.) Nutt., is known as the 'headache tree' because the inhalation of its vapours can cause severe headache crises. However, the underlying mechanism of the headache precipitating properties of Umbellularia californica is unknown. The monoterpene ketone umbellulone, the major volatile...
Article
hPAR(2) (human proteinase-activated receptor-2) is a member of the novel family of proteolytically activated GPCRs (G-protein-coupled receptors) termed PARs (proteinase-activated receptors). Previous pharmacological studies have found that activation of hPAR(2) by mast cell tryptase can be regulated by receptor N-terminal glycosylation. In order to...
Article
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Proteinase-activated receptor 1 (PAR1) induces activation of platelet and vascular cells after proteolytic cleavage of its extracellular N terminus by thrombin. In pathological situations, other proteinases may be generated in the circulation and might modify the responses of PAR1 by cleaving extracellular domains. In this study, epitope-tagged wil...
Article
The nociceptor TRPA1 is thought to be activated through covalent modification of specific cysteine residues on the N terminal of the channel. The precise mechanism of covalent modification with unsaturated carbonyl-containing compounds is unclear, therefore by examining a range of compounds which can undergo both conjugate and/or direct addition re...
Article
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Acetaminophen [N-acetyl-p-aminophenol (APAP)] is the most common antipyretic/analgesic medicine worldwide. If APAP is overdosed, its metabolite, N-acetyl-p-benzo-quinoneimine (NAPQI), causes liver damage. However, epidemiological evidence has associated previous use of therapeutic APAP doses with the risk of chronic obstructive pulmonary disease (C...
Article
Cough is the most frequent reason for consultation with a family doctor, or with a general or respiratory physician. Treatment options are limited and one meta-analysis concluded that over-the-counter remedies are ineffective. There is also increasing concern about their use in children. Environmental irritants such as air pollution and cigarette s...
Article
Full-text available
American guidelines, unlike European guidelines, support the use of antihistamines as a first line of treatment for some causes of chronic cough. Transient receptor potential vanilloid-1 (TRPV1) is an ion channel activated by the tussive agents capsaicin, resiniferatoxin, and protons. It is predominantly expressed by C-fiber and some Adelta -fiber...
Article
Human lung fibroblasts express proteinase-activated receptor-1 (PAR1), PAR2 and PAR3, but not PAR4. Because PAR2 has inflammatory effects on human primary bronchial fibroblasts (HPBF), we asked 1) whether the inflammatory mediators TNF-alpha and LPS could modify HPBF PAR expression and 2) whether modified PAR expression altered HPBF responsiveness...
Article
TRPV1 is a modulator of noxious stimuli known to be important in the cough reflex. We have compared the expression of TRPV1 in normal human airways and those from patients with chronic cough and found that there is up regulation in airways smooth muscle in disease. This increased expression appears to be intracellular and we have therefore examined...

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