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Biomedical subjects

J Mark Madison

Publications and source records attributed to J Mark Madison.

12 recordsLinked to original sources
PubMed2006

Adenosine A1 receptors mediate mobilization of calcium in human bronchial smooth muscle cells.

Adenosine stimulates contraction of airway smooth muscle, but the mechanism is widely considered indirect, depending on release of contractile agonists from mast cells and nerves. The goal was to determine whether adenosine, by itself, directly regulates calcium signaling in human bronchial smooth muscle cells (HBSMC). Primary cultures of HBSMC from normal subjects were loaded with fura 2-AM, and cytosolic calcium concentrations ([Ca(2+)](i)) were determined ratiometrically by imaging single cells. The nonselective adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA), and the adenosine A(1) receptor agonist, N(6)-cyclopentyladenosine (CPA), both stimulated rapid, transient increases in [Ca(2+)](i). In contrast, there were no calcium responses to 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido-adenosine (100 nM) or N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (100 nM), selective agonists at adenosine A(2A) receptors and adenosine A(3) receptors, respectively. Calcium responses to NECA and CPA were inhibited by 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A(1) receptor antagonist, and by pertussis toxin (PTX). In other experiments, NECA stimulated calcium transients in the absence of extracellular calcium, but not when cells were preincubated in cyclopiazonic acid or thapsigargin to empty intracellular calcium stores. Calcium responses were attenuated by xestospongin C and 2-aminoethoxydiphenylborane, inhibitors of inositol trisphosphate (IP(3)) receptors, and by U73122, an inhibitor of phospholipase C. It was concluded that stimulation of adenosine A(1) receptors on HBSMC rapidly mobilizes intracellular calcium stores by a mechanism dependent on PTX-sensitive G proteins, and IP(3) signaling. These findings suggest that, in addition to its well-established indirect effects on HBSMC, adenosine also has direct effects on contractile signaling pathways.

Adenosine A1 Receptor Antagonists↗
PubMed2005

IL-4 inhibits calcium transients in bovine trachealis cells by a ryanodine receptor-dependent mechanism.

IL-4 and IL-13 have important roles in the pathogenesis of asthma. A novel finding was that brief exposure of airway smooth muscle cells to IL-4 inhibited carbachol-stimulated calcium transients. We hypothesized that IL-4 inhibits transients by decreasing calcium store content and tested this by measuring the effects of IL-4 on transients induced by a nonspecific ionophore. Bovine trachealis cells were loaded with fura 2-AM, and cytosolic calcium concentrations ([Ca2+]i) were measured in single cells by digital microscopy. Stimulation (S1) with carbachol (10 microM) caused rapid, transient increases in [Ca2+]i to 1299 +/- 355 nM (n=5). After recovery of calcium stores, stimulation (S2) of the same cells with ionomycin (10 microM), in the absence of extracellular calcium, also increased [Ca2+]i to give S2/S1 ratio of 1.03 +/- 0.29. However, after 20 min of IL-4 (50 ng/ml), but not IL-13, ionomycin transients were decreased to 0.50 +/- 0.16 (S2/S1, P=0.02, n=6). IL-4 did not inhibit transients with ryanodine receptor calcium release channels (RyR) blocked by ryanodine (200 microM) (S2/S1=1.01+/-0.11) but still did in the presence of 8-bromo cyclic ADP-ribose, an antagonist of cyclic ADP-ribose (cADPR) signaling at RyR (S2/S1=0.48+/-0.13). Together, findings suggest that IL-4 decreases intracellular calcium stores by mechanisms dependent on RyR, but not on cADPR signaling.

Animals↗
PubMed2005

Mechanisms of interleukin-4 effects on calcium signaling in airway smooth muscle cells.

In airway smooth muscle cells, interleukin (IL)-4 inhibited both carbachol- and caffeine-induced calcium mobilization from the sarcoplasmic reticulum (SR). Because of the known signaling pathways for IL-4 and importance of calcium uptake in maintaining SR calcium stores shared by agonists and caffeine, it was hypothesized that this rapid inhibitory effect might depend on phosphatidylinositol 3-kinase (PI3K) and on inhibition of calcium uptake by the SR. Enzyme-dispersed bovine trachealis cells were loaded with Fura-2/acetoxymethyl ester, and changes in cytosolic calcium were imaged in single cells. Cells were pretreated with inhibitors of PI3K, either wortmannin (100 nM), LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] (50 microM), or deguelin (100 nM). Calcium transients in response to carbachol (10 microM) were significantly decreased to 0.34 +/- 0.10 of control after 20-min treatment with IL-4 but were 1.10 +/- 0.26 and 1.08 +/- 0.23 when wortmannin or deguelin, respectively, was added along with IL-4. LY294002 alone had nonspecific effects on transients. In other experiments, cyclopiazonic acid (CPA) (5 microM), an inhibitor of SR calcium uptake, decreased carbachol-stimulated transients within 4 min to 0.83 +/- 0.08 of control (n = 6). However, for cells treated with IL-4 (50 ng/ml) plus CPA, transients decreased significantly more, to only 0.51 +/- 0.05 (n = 6; p < 0.05). Longer exposures to IL-4 and a higher concentration of CPA (30 microM) gave similar results. It was concluded that IL-4 did not inhibit transients in the presence of PI3K antagonists but that it did in the presence of CPA. This suggested that IL-4 inhibited calcium transients by mechanisms dependent upon a wortmannin-sensitive PI3K but not by inhibition of calcium uptake into the SR.

Animals↗
PubMed2005

Chronic cough in adults with interstitial lung disease.

PURPOSE OF REVIEW: Although dyspnea is the most common and distressing symptom in patients with chronic interstitial lung disease, chronic cough, a potentially debilitating symptom that impairs health-related quality of life, has been described as another common symptom in these patients. RECENT FINDINGS: Many patients with interstitial lung disease have their chronic cough mistakenly attributed to that condition when, in fact, the cough is due to more common disorders such as asthma, upper airway cough syndrome (previously referred to as postnasal drip syndrome), or gastroesophageal reflux disease. This article presents new data on a select group of patients and shows that more than 50% of patients with interstitial lung disease who are referred to a cough clinic for evaluation can have cough caused by these other more common causes of chronic cough. It is also clear, however, that chronic interstitial lung disease, by itself, can cause chronic cough, perhaps related to an increased cough reflex sensitivity. SUMMARY: Clinicians should be cautious when ascribing chronic cough to interstitial lung disease without first completely evaluating for other possible causes of cough. When cough is attributed to interstitial lung disease, therapy, when available, should be directed at the specific underlying diagnosis. Corticosteroids may be helpful in alleviating chronic cough in some cases of interstitial lung disease, but, because of the potential side effects of corticosteroids and lack of proven efficacy for some types of interstitial lung disease (e.g. idiopathic pulmonary fibrosis), treatment should weigh the risks and benefits for each patient individually. Nonspecific antitussive therapies shown to be clinically effective for chronic cough in general are codeine and dextromethorphan, but these have not been studied specifically in interstitial lung disease.

Chronic Disease↗
PubMed2003

Pharmacotherapy of chronic cough in adults.

Chronic cough is a debilitating symptom for which patients commonly seek medical attention. Among adult non-smokers who are not taking an angiotensin-converting enzyme inhibitor and have a normal or near normal chest radiograph, postnasal drip syndrome caused by a variety of rhinosinus conditions, asthma and non-asthmatic eosinophilic bronchitis and gastro-oesophageal reflux disease singly or in combination, are the most common diagnoses underlying chronic cough. Pharmacotherapy for chronic cough can be either specific or non-specific. Specific therapy is preferable and the most effective as it is directed at the aetiologies and pathophysiological mechanisms responsible for cough. In contrast, non-specific therapy is used only in limited clinical settings, as it is directed at the symptom rather than underlying aetiologies and aims only to control, rather than eliminate cough.

Adult↗
PubMed2002

Diagnosis and treatment of chronic cough due to gastro-esophageal reflux disease and postnasal drip syndrome.

Gastro-esophageal reflux disease (GERD) and postnasal drip syndrome (PNDS) are common causes of chronic cough. In patients with normal chest radiographs, GERD most likely causes cough by an esophageal-bronchial reflex. When GERD causes cough, there may be no gastrointestinal symptoms up to 75% of the time. While 24-h esophageal pH monitoring is the most sensitive and specific test in linking GERD and cough in a cause and effect relationship, it has its limitations. There is no general agreement on how to best interpret the test and it cannot detect non-acid reflux events. While some patients improve with minimal medical therapy, others require intensive regimens. Surgery may be efficacious when intensive medical therapy has failed. Because there are no pathognomonic findings of PNDS, the diagnosis is inferential and is based upon a combination of clinical findings, the results of ancillary testing, and the response to specific therapy. Specific therapy depends upon the rhinosinus disease(s) causing the PND. A common error in managing PNDSs is to assume that all H(1)-antagonists are equally efficacious. The second-generation, relatively non-sedating H(1)-antagonists have been found to be less effective than the first-generation agents in treating cough due to non-histamine-mediated PNDSs.

Antigens, Helminth↗
PubMedDate not supplied

Applicability of prediction rules in patients with community-acquired pneumonia requiring intensive care: a pilot study.

Little attention has been paid to developing prediction rules that could assist in deciding which patients with community-acquired pneumonia (CAP) need intensive care. Four existing prediction rules were examined to determine if any could predict the need for intensive care in these patients. The prediction rules studied were British Thoracic Society (BTS), Conte et al, Leroy et al, and Fine et al. Thirty-two patients admitted to the medical or coronary intensive care unit (ICU) during 1 year with pneumonia Diagnosis Related Group 079 or 089 were evaluated. The sensitivity of each rule for identifying a need for ICU admission in our group was BTS .72 using both rules together, Conte et al .47, Leroy et al .56, and Fine et al .84. It was concluded that these rules poorly identify the need for ICU admission for patients with severe CAP. Of the 4 rules tested, the BTS rule was the simplest, and the Fine et al rule was the most sensitive. None of them performed well enough to be used for decision making in individual patients.

Adult↗