7 results on '"Simcock, David E."'
Search Results
2. Induction of Angiogenesis by Airway Smooth Muscle From Patients with Asthma
- Author
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Simcock, David E., Kanabar, Varsha, Clarke, Graham W., Mahn, Katharina, Karner, Charlotta, OʼConnor, Brian J., Lee, Tak H., and Hirst, Stuart J.
- Published
- 2008
- Full Text
- View/download PDF
3. Proangiogenic Activity in Bronchoalveolar Lavage Fluid from Patients with Asthma
- Author
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Simcock, David E., Kanabar, Varsha, Clarke, Graham W., OʼConnor, Brian J., Lee, Tak H., and Hirst, Stuart J.
- Published
- 2007
- Full Text
- View/download PDF
4. Diminished sarco/endoplasmic reticulum Ca 2+ ATPase (SERCA) expression contributes to airway remodelling in bronchial asthma
- Author
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Mahn, Katharina, primary, Hirst, Stuart J., additional, Ying, Sun, additional, Holt, Mark R., additional, Lavender, Paul, additional, Ojo, Oluwaseun O., additional, Siew, Leonard, additional, Simcock, David E., additional, McVicker, Clare G., additional, Kanabar, Varsha, additional, Snetkov, Vladimir A., additional, O'Connor, Brian J., additional, Karner, Charlotta, additional, Cousins, David J., additional, Macedo, Patricia, additional, Chung, K. Fan, additional, Corrigan, Christopher J., additional, Ward, Jeremy P. T., additional, and Lee, Tak H., additional
- Published
- 2009
- Full Text
- View/download PDF
5. Diminished sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) expression contributes to airway remodelling in bronchial asthma.
- Author
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Mahn, Katharina, Hirst, Stuart J., Sun Ying, Holt, Mark R., Lavender, Paul, Ojo, Oluwaseun O., Siew, Leonard, Simcock, David E., McVicker, Clare G., Kanabar, Varsha, Snetkov, Vladimir A., O'Connor, Brian J., Karner, Charlotta, Cousins, David J., Macedo, Patricia, Fan Chung, K., Corrigan, Christopher J., Ward, Jeremy P. T., and Lee, Tak H.
- Subjects
ASTHMA ,ENDOPLASMIC reticulum ,ADENOSINE triphosphate ,IMMUNOHISTOCHEMISTRY ,INFLAMMATORY mediators - Abstract
Phenotypic modulation of airway smooth muscle (ASM) is an important feature of airway remodeling in asthma that is characterized by enhanced proliferation and secretion of pro-inflammatory chemokines. These activities are regulated by the concentration of free Ca
2+ in the cytosol ([Ca2+ ]i ). A rise in [Ca2+ ]i is normalized by rapid reuptake of Ca2+ into sarcoplasmic reticulum (SR) stores by the sarco/endoplasmic reticulum Ca2+ (SERCA) pump. We examined whether increased proliferative and secretory responses of ASM from asthmatics result from reduced SERCA expression. ASM cells were cultured from subjects with and without asthma. SERCA expression was evaluated by western blot, immunohistochemistry and real-time PCR. Changes in [Ca2+ ]i , cell spreading, cellular proliferation, and eotaxin-1 release were measured. Compared with control cells from healthy subjects, SERCA2 mRNA and protein expression was reduced in ASM cells from subjects with moderately severe asthma. SERCA2 expression was similarly reduced in ASM in vivo in subjects with moderate/severe asthma. Rises in [Ca2+ ]i following cell surface receptor-induced SR activation, or inhibition of SERCA-mediated Ca2+ re-uptake, were attenuated in ASM cells from asthmatics. Likewise, the return to baseline of [Ca]i after stimulation by bradykinin was delayed by approximately 50% in ASM cells from asthmatics. siRNA-mediated knockdown of SERCA2 in ASM from healthy subjects increased cell spreading, eotaxin-1 release and proliferation. Our findings implicate a deficiency in SERCA2 in ASM in asthma that contributes to its secretory and hyperproliferative phenotype in asthma, and which may play a key role in mechanisms of airway remodeling. [ABSTRACT FROM AUTHOR]- Published
- 2009
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- View/download PDF
6. Prevalence, determinants and clinical correlates of vitamin D deficiency in patients with Chronic Obstructive Pulmonary Disease in London, UK
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Chris Griffiths, Richard Hooper, Aklak Choudhury, Claire L. Greiller, Christopher Corrigan, David A. Jolliffe, Wai Yee James, Elina Hyppönen, Angshu Bhowmik, David E. Simcock, Kamrul Islam, Peter Timms, Neil Barnes, Raj K Rajakulasingam, Robert Walton, Adrian R. Martineau, Jolliffe, David A, James, Wai Yee, Hooper, Richard L, Barnes, Neil C, Greiller, Claire L, Islam, Kamrul, Bhowmik, Angshu, Timms, Peter M, Rajakulasingam, Raj K, Choudhury, Aklak B, Simcock, David E, Hyppönen, Elina, Walton, Robert T, Corrigan, Christopher J, Griffiths, Christopher J, Martineau, Adrian R, and 5th International Conference on Vitamin D Deficiency, Nutrition and Human Health Abu Dhabi, U Arab Emirates 24-25 March 2016
- Subjects
Male ,Vital capacity ,Neutrophils ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,spirometry ,vitamin D ,Biochemistry ,Gastroenterology ,Calcitriol receptor ,Severity of Illness Index ,Body Mass Index ,FEV1 ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Endocrinology ,Cytochrome P-450 Enzyme System ,single nucleotide polymorphism ,London ,Prevalence ,030212 general & internal medicine ,Vitamin D ,Aged, 80 and over ,COPD ,medicine.diagnostic_test ,Continental Population Groups ,Middle Aged ,Respiratory Function Tests ,DNA-Binding Proteins ,Low Density Lipoprotein Receptor-Related Protein-2 ,Molecular Medicine ,Female ,medicine.symptom ,Spirometry ,Adult ,medicine.medical_specialty ,Oxidoreductases Acting on CH-CH Group Donors ,Receptors, Cell Surface ,vitamin D deficiency ,03 medical and health sciences ,FEV1/FVC ratio ,Endocrinology & Metabolism ,Internal medicine ,medicine ,Vitamin D and neurology ,Humans ,Molecular Biology ,Aged ,business.industry ,Racial Groups ,0601 Biochemistry And Cell Biology ,Cell Biology ,medicine.disease ,Vitamin D Deficiency ,FVC ,respiratory tract diseases ,Single nucleotide polymorphism ,Eosinophils ,Cross-Sectional Studies ,030228 respiratory system ,Gene Expression Regulation ,Immunology ,Sputum ,Receptors, Calcitriol ,business ,Transcription Factors - Abstract
Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease (COPD), yet a comprehensive analysis of environmental and genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration in patients with this condition is lacking. We conducted a multi-centre cross-sectional study in 278 COPD patients aged 41–92 years in London, UK. Details of potential environmental determinants of vitamin D status and COPD symptom control and severity were collected by questionnaire, and blood samples were taken for analysis of serum 25(OH)D concentration and DNA extraction. All participants perform ed spirometry and underwent measurement of weight and height. Quadriceps muscle strength (QS) was measured in 134 participants, and sputum induction with enumeration of lower airway eosinophil and neutrophil counts was performed for 44 participants. Thirty-seven single nucleotide polymorphisms (SNP) in 11 genes in the vitamin D pathway (DBP, DHCR7, CYP2R1, CYP27B1, CYP24A1, CYP27A1, CYP3A4, LRP2, CUBN, RXRA, and VDR) were typed using Taqman allelic discrimination assays. Linear regression was used to identify environmental and genetic factors independently associated with serum 25(OH)D concentration and to determine whether vitamin D status or genetic factors independently associated with % predicted forced expiratory volume in one second (FEV 1 ), % predicted forced vital capacity (FVC), the ratio of FEV 1 to FVC (FEV 1 :FVC), daily inhaled corticosteroid (ICS) dose, respiratory quality of life (QoL), QS, and the percentage of eosinophils and neutrophils in induced sputum. Mean serum 25(OH)D concentration was 45.4 nmol/L (SD 25.3); 171/278 (61.5%) participants were vitamin D deficient (serum 25[OH]D concentration < 50 nmol/L). Lower vitamin D status was independently associated with higher body mass index (P = 0.001), lower socio-economic position (P = 0.037), lack of vitamin D supplement consumption (P < 0.001), sampling in Winter or Spring (P for trend = 0.006) and lack of a recent sunny holiday (P = 0.002). Vitamin D deficiency associated with reduced % predicted FEV 1 (P for trend = 0.060) and % predicted FVC (P for trend = 0.003), but it did not associate with FEV 1 :FVC, ICS dose, QoL, QS, or the percentage of eosinophils or neutrophils in induced sputum. After correction for multiple comparisons testing, genetic variation in the vitamin D pathway was not found to associate with serum 25(OH)D concentration or clinical correlates of COPD severity. Vitamin D deficiency was common in this group of COPD patients in the UK, and it associated independently with reduced % predicted FEV1 and FVC. However, genetic variation in the vitamin D pathway was not associated with vitamin D status or severity of COPD. Refereed/Peer-reviewed
- Published
- 2017
7. Prevalence, determinants and clinical correlates of vitamin D deficiency in adults with inhaled corticosteroid-treated asthma in London, UK
- Author
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Beverley MacLaughlin, Aklak Choudhury, Kate Kilpin, Christopher Corrigan, Adrian R. Martineau, Claire L. Greiller, Peter Timms, Chris Griffiths, Richard Hooper, Neil Barnes, Raj K Rajakulasingam, Robert Walton, Elina Hyppönen, David A. Jolliffe, Angshu Bhowmik, David E. Simcock, Jolliffe, David A, Kilpin, Kate, MacLaughlin, Beverley D, Greiller, Claire L, Hooper, Richard L, Barnes, Neil C, Timms, Peter M, Rajakulasingam, Raj K, Bhowmik, Angshu, Choudhury, Aklak B, Simcock, David E, Hyppönen, Elina, Corrigan, Christopher J, Walton, Robert T, Griffiths, Christopher J, and Martineau, Adrian R
- Subjects
Male ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Biochemistry ,Calcitriol receptor ,Gastroenterology ,Severity of Illness Index ,environmental ,Body Mass Index ,0302 clinical medicine ,Endocrinology ,Cytochrome P-450 Enzyme System ,Adrenal Cortex Hormones ,London ,genetics ,030212 general & internal medicine ,Anti-Asthmatic Agents ,Vitamin D ,education.field_of_study ,medicine.diagnostic_test ,Middle Aged ,Respiratory Function Tests ,DNA-Binding Proteins ,Low Density Lipoprotein Receptor-Related Protein-2 ,Molecular Medicine ,Female ,Spirometry ,Adult ,medicine.medical_specialty ,Oxidoreductases Acting on CH-CH Group Donors ,cross-sectional ,Adolescent ,phenotype ,Population ,Receptors, Cell Surface ,vitamin D deficiency ,03 medical and health sciences ,FEV1/FVC ratio ,Internal medicine ,Administration, Inhalation ,medicine ,Vitamin D and neurology ,Humans ,education ,Molecular Biology ,Asthma ,Aged ,business.industry ,Racial Groups ,Cell Biology ,asthma ,medicine.disease ,Vitamin D Deficiency ,respiratory tract diseases ,Eosinophils ,Cross-Sectional Studies ,030228 respiratory system ,Gene Expression Regulation ,Immunology ,Exhaled nitric oxide ,Receptors, Calcitriol ,business ,Transcription Factors - Abstract
Vitamin D deficiency is common in children with asthma, and it associates with poor asthma control, reduced forced expiratory volume in one second (FEV1) and increased requirement for inhaled corticosteroids (ICS). Cross-sectional studies investigating the prevalence, determinants and clinical correlates of vitamin D deficiency in adults with asthma are lacking. We conducted a multi-centre cross-sectional study in 297 adults with a medical record diagnosis of ICS-treated asthma living in London, UK. Details of potential environmental determinants of vitamin D status, asthma control and medication use were collected by questionnaire; blood samples were taken for analysis of serum 25(OH)D concentration and DNA extraction, and participants underwent measurement of weight, height and fractional exhaled nitric oxide concentration (FeNO), spirometry and sputum induction for determination of lower airway eosinophil counts (n=35 sub-group). Thirty-five single nucleotide polymorphisms (SNP) in 11 vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4 CYP27A1, LRP2, CUBN, VDR) were typed using Taqman allelic discrimination assays. Linear regression was used to identify environmental and genetic factors independently associated with serum 25(OH)D concentration, and to determine whether vitamin D status was independently associated with Asthma Control Test (ACT) score, ICS dose, FeNO, forced vital capacity (FVC), FEV1 or lower airway eosinophilia. Mean serum 25(OH)D concentration was 50.6nmol/L (SD 24.9); 162/297 (54.5%) participants were vitamin D deficient (serum 25(OH)D concentration
- Published
- 2016
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