Brent McParland - Academia.edu (original) (raw)

Papers by Brent McParland

Key:ASMC = airway smooth muscle cells; HB... more Key:ASMC = airway smooth muscle cells; HBEC = human bronchial epithelial cells; SCCA = Small cell carcinoma; NSCCA = Non small cell carcinoma; COPD = Chronic obstructive pulmonary disease; Ca = Cancer.</p

ASMCs (n = 5) were pretreated for 1 hr with appropriate vehicles or indomethacin (10<... more ASMCs (n = 5) were pretreated for 1 hr with appropriate vehicles or indomethacin (10−5 M) (A,B), celecoxib (10−5 M) (C,D) or a combination of prostaglandin receptor antagonists (combination composition: AH6809 (10−5 M); CAY10441 (10−6 M); AL8810 (10−5 M); BWA868C (10−5 M); L-161,982 (10−6 M)) (E) and maintained for a further 3 days in the presence of conditioned medium from HBEC (n = 1) that were uninfected (Control) or exposed to: UV inactivated RV (UVi-RV) or replication competent RV (RV) at an MOI = 2 for 24 hours. PGE2 (A, C) was measured using ELISA and isoprenaline induced cAMP (B, D, E) was measured using a cAMP functional assay. Data represent mean ± SEM. Statistical differences were detected using 1-way ANOVA with Bonferroni post test comparisons to control conditioned medium pretreatment in each group *p<0.05.</p

Demographic data of study patients in RV infection of airway structural cells and prosta... more Demographic data of study patients in RV infection of airway structural cells and prostaglandin production.</p

Journal of applied physiology (Bethesda, Md. : 1985), 2003

Smooth muscle exhibits biophysical characteristics and physiological behaviors that are not readi... more Smooth muscle exhibits biophysical characteristics and physiological behaviors that are not readily explained by present paradigms of cytoskeletal and cross-bridge mechanics. There is increasing evidence that contractile activation of the smooth muscle cell involves an array of cytoskeletal processes that extend beyond cross-bridge cycling and the sliding of thick and thin filaments. We review here the evidence suggesting that the biophysical and mechanical properties of the smooth muscle cell reflect the integrated interactions of an array of highly dynamic cytoskeletal processes that both react to and transform the dynamics of cross-bridge interactions over the course of the contraction cycle. The activation of the smooth muscle cell is proposed to trigger dynamic remodeling of the actin filament lattice within cellular microdomains in response to local mechanical and pharmacological events, enabling the cell to adapt to its external environment. As the contraction progresses, the...

Drug Development and Industrial Pharmacy

European Respiratory Journal, 1998

European Journal of Pharmacology, 2000

We have previously reported, using a novel preparation of canine airway segments, that the sensit... more We have previously reported, using a novel preparation of canine airway segments, that the sensitivity of acetylcholine was greater Ž. Ž. when applied to the adventitial outside surface than the epithelial inside surface. The present study investigated if this Abarrier-effectB was partly the result of pharmacological modulation by the epithelium. As previously demonstrated, canine airway segments were less Ž. sensitive to inside than outside application of acetylcholine pD 3.0 " 0.4 and 4.5 " 0.4, respectively, P-0.001, n s 5. The addition 2 Ž of donor bronchi significantly decreased the sensitivity of the airway segment to outside application of acetylcholine pD 4.3 " 0.2 and 2. Ž. 3.6 " 0.2, respectively, P-0.002, n s 4. Indomethacin 2.5 mM treatment of both the donor bronchi and the airway segment and removal of donor epithelium abolished the rightward shift in the acetylcholine-response curves. In addition, inhibition of cyclooxygenase within the airway segments themselves, but not the donor bronchi, also inhibited the rightward shift in the curves. These results indicate that the donor epithelium is capable of pharmacologically modulating responses of the airway segment to outside applied acetylcholine by producing an epithelial-derived factor, which in turn causes the release of a downstream cyclooxygenase product from within the airway segment.

American Journal of Respiratory Cell and Molecular Biology, 2010

Rhinovirus (RV) infections are the major cause of asthma exacerbations in children and adults. Un... more Rhinovirus (RV) infections are the major cause of asthma exacerbations in children and adults. Under normal circumstances, asthmatic airway obstruction improves spontaneously or characteristically briskly in response to inhaled beta(2)-adrenergic receptor (beta(2)AR) agonists. During virus-associated exacerbations, an impaired response to beta(2)AR agonists is observed; the reason for this is not known. The objective of this study was to determine the effect of RV infection on airway smooth muscle beta(2)AR function. The human cell line Beas-2B and primary human bronchial epithelial cells (HBECs) were infected with RV (multiplicity of infection = 1). After 1 or 5 days for primary and Beas-2B cells, respectively, cell culture supernatants were harvested, UV-irradiated to inactivate RV, and applied to human airway smooth muscle cells for 3 days to assess modifications of beta(2)AR function. RV conditioned medium from Beas-2B and HBECs decreased beta(2)AR agonist-induced cAMP by 50 and 65%, respectively (n = 5; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). When cAMP was induced independently of the beta(2)AR using forskolin, no impairment was found. Using flow cytometry, we demonstrated that this decrease was likely the result of beta(2)AR desensitization because membrane but not total cell receptor beta(2)AR was decreased. Pretreatment of HBECs and Beas-2B cells but not human airway smooth muscle cells with the corticosteroids dexamethasone or fluticasone abolished virus-mediated beta(2)AR loss of function. This study shows that epithelial infection with RV induces a decrease of beta(2)AR function on airway smooth muscle cells, potentially explaining the clinical observation of loss of beta(2)AR agonist function during RV-induced asthma exacerbations.

American Journal of Respiratory and Critical Care Medicine, Dec 20, 2012

Airway pharmacology and treatment

Ticks and tick-borne diseases, Mar 1, 2018

Babesia and Theileria are intraerythrocytic protozoans of the phylum Apicomplexa. These species a... more Babesia and Theileria are intraerythrocytic protozoans of the phylum Apicomplexa. These species are capable of infecting wild and domestic animals and have historically caused great economic loss in the agricultural industry. In recent years human babesiosis has been deemed an emerging zoonosis in North America, Europe and Asia. The first locally acquired case of babesiosis in Australia, caused by Babesia microti, was reported in March 2012. A number of native Babesia and Theileria species have been identified in Australian marsupials, however their associated tick vectors and threat to human health is unknown. In the present study DNA was extracted from 1154 ticks collected from across Australia. PCR was used to amplify a Babesia and Theileria-specific partial region of the 18S ribosomal RNA gene. Positive samples were sequenced and phylogenetic analysis was performed. Twenty-nine sequences were obtained from ticks belonging to the genera Ixodes, Haemaphysalis and Bothriocroton. Th...

European Respiratory Journal, Sep 1, 2013

American Journal of Respiratory Cell and Molecular Biology, Dec 20, 2012

Excessive narrowing of airways in response to contractile agonists is a characteristic feature of... more Excessive narrowing of airways in response to contractile agonists is a characteristic feature of asthma. We hypothesized that airway smooth muscle (ASM) adaptation to short lengths could contribute to exaggerated airway narrowing during an acute attack of asthma by allowing the muscle to regain its ability to generate maximal force at a shortened length. To test this hypothesis we mimicked, in vitro, the sequence of contractile events that would occur during a spontaneous attack of asthma. Trachealis muscle was challenged with carbachol (300 nM, submaximal dose) and allowed to shorten to approximately half of its original length. After 30 min of adaptation at the shortened length in the presence of carbachol, muscle force, amount and rate of shortening in response to electrical stimulation were compared with corresponding values obtained from control experiments during which the ASM was not adapted to the short length. After adaptation at the shortened length the developed force, amount and rate of shortening increased by 1.93 +/- 0.08-, 1.57 +/- 0.12-, and 1.75 +/- 0.2-fold, respectively. Shortening of ASM in response to contractile agonists can lead to adaptation of the muscle to the shortened length that, in turn, can result in further shortening and the potential for airway closure.

Canadian Journal of Physiology and Pharmacology, Aug 1, 2007

Airway hyperresponsiveness, particularly the ability of airways to narrow excessively in response... more Airway hyperresponsiveness, particularly the ability of airways to narrow excessively in response to stimuli that normally cause little airway narrowing in nonasthmatic subjects, is a characteristic feature of asthma and the basis of its symptoms. Although airway hyperresponsiveness may be partly the result of alterations in the contractile phenotype of the airway smooth muscle, there is evidence that it may also be caused by structural changes in the airway wall, collectively termed airway remodeling. Airway remodeling is defined as changes in composition, quantity, and (or) organization of cellular and molecular constituents of the airway wall. Airway wall remodeling that occurs in asthma can result in functional alterations because of quantitative changes in airway wall compartments, and (or) because of changes in the biochemical composition or material properties of the various constituents of the airway wall. This brief review summarizes the quantitative changes in the dimensions and organization of the airway wall compartments that have been described and explains how structural alterations may lead to the exaggerated airway narrowing.

American Journal of Respiratory and Critical Care Medicine, 2003

Journal of Applied Physiology, 2006

Strips of rabbit detrusor smooth muscle (DSM) exhibit adjustable passive stiffness characterized ... more Strips of rabbit detrusor smooth muscle (DSM) exhibit adjustable passive stiffness characterized by strain softening: a loss of stiffness on stretch to a new length distinct from viscoelastic behavior. At the molecular level, strain softening appears to be caused by cross-link breakage and is essentially irreversible when DSM is maintained under passive conditions (i.e., when cross bridges are not cycling to produce active force). However, on DSM activation, strain softening is reversible and likely due to cross-link reformation. Thus DSM displays adjustable passive stiffness that is dependent on the history of both muscle strain and activation. The present study provides empirical data showing that, in DSM, 1) passive isometric force relaxation includes a very slow component requiring hours to approach steady state, 2) the level of passive force maintained at steady state is less if the tissue has previously been strain softened, and 3) tissues subjected to a quick-release protocol...