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Biomedical subjects

J Courtney

Publications and source records attributed to J Courtney.

13 recordsLinked to original sources
PubMed2005

Neutrophil cell death, activation and bacterial infection in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is characterised by chronic endobronchial bacterial infection and neutrophil mediated inflammation. Neutrophil apoptosis is essential for the resolution of inflammation. This study assessed the relationship between levels of neutrophil apoptosis and sputum microbiology in matched clinically stable patients with CF. METHODS: Sputum was induced from 34 patients (nine with no Gram negative infection, 10 colonised with Pseudomonas aeruginosa, 10 with Burkholderia cenocepacia, and five with other infections). Apoptotic neutrophils measured by flow cytometric Annexin V/propidium iodide staining and morphology were similar in all groups. RESULTS: Patients infected with P aeruginosa or B cenocepacia had a significantly lower percentage of viable neutrophils in the sputum than those with no Gram negative infection (Kruskal-Wallis p = 0.01, median (interquartile range (IQR)) 14.2% (9.4-21.6), 15.8% (12.3-19.5), and 48.4% (23.0-66.4); p = 0.003 and p = 0.002, respectively). They also had significantly higher levels of secondary necrotic granulocytes in sputum than patients with no Gram negative infection (Kruskal-Wallis p<0.0001, median (IQR) 55.5% (48.4-64.5), 50.4% (44.6-61.9), and 24.8% (14.4-30.5); p<0.0001 and p<0.0001, respectively). Neutrophils (x 10(6)/g sputum) in P aeruginosa infected patients (Kruskal-Wallis p = 0.05, median (IQR) 6.3 (3.5-12.7)) and B cenocepacia infected patients (5.7 (1.5-14.5)) were significantly higher than in the group with no Gram negative infection (0.5 (0.5-4.3), p = 0.03 and 0.04, respectively). CONCLUSION: These results suggest that cell death and clearance may be altered in patients with CF colonised with P aeruginosa and B cenocepacia compared with those with no Gram negative infection.

Adult↗
PubMed2004

Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis.

BACKGROUND: Lower airway secretions from patients with bronchiectasis show inflammatory cell infiltration and increased proinflammatory mediators. The aim of this study was to investigate the effects of antibiotic treatment for exacerbations on neutrophil apoptosis and necrosis. METHODS: Sputum was induced from 15 subjects with idiopathic bronchiectasis at the beginning of an acute exacerbation and after intravenous antibiotic treatment. Neutrophil apoptosis and necrosis were assessed using flow cytometry and morphology and the supernatant was analysed for concentrations of inflammatory mediators. RESULTS: Neutrophil numbers (x10(6) cells/g sputum) in sputum were significantly greater on day 0 than on day 14 (median difference (95% confidence interval (CI)) 5.14 (1.27 to 8.46), p = 0.02). Controls had a significantly higher percentage of sputum macrophages than patients with bronchiectasis (day 0, 1.35 (95% CI 0.48 to 2.89), p = 0.004; day 14, 1.09 (95% CI 0.26 to 2.86), p = 0.02). The concentrations of tumour necrosis factor alpha (pg/ml), interleukin 8 (ng/ml), and neutrophil elastase (ng/ml) in sputum supernatant were significantly reduced on day 14 compared with day 0 (median difference -94 (95% CI -158 to -27), p = 0.005; -106 (95% CI -189 to -50), p = 0.0006; and -73 451 (95% CI -135 495 to -12 303), p = 0.02 respectively). Patients with bronchiectasis had a significantly lower percentage of cells which were neither apoptotic nor necrotic than healthy controls (both days, -38.8 (95% CI -49.6 to -8.5), p = 0.002; -45.0 (95% CI -58.0 to -34.1), p = 0.0003, respectively), and on day 14 they had a significantly higher percentage of secondary necrotic cells than healthy controls (40 (95% CI 11.6 to 57.5), p = 0.004). CONCLUSIONS: This study shows that antibiotic treatment affects concentrations of proinflammatory mediators and cell death and clearance may be altered in bronchiectasis.

Anti-Infective Agents↗
PubMed2003

Development of a Gram-negative selective agar (GNSA) for the detection of Gram-negative microflora in sputa in patients with cystic fibrosis.

AIMS: To develop a selective agar medium to help detect and quantify Gram-negative flora in the sputum of patients with cystic fibrosis (CF). METHODS AND RESULTS: A novel Gram-negative Selective Agar (GNSA) medium was developed consisting of tryptone soya broth (30 g), bacteriological agar no.1 (10 g), yeast extract (5 g), crystal violet (2 mg), nisin (48 mg), novobiocin (5 mg), cycloheximide (100 mg), amphotericin (2 mg) and double distilled water (1 l), for the selective culture of all Gram-negative flora from the sputum of patients with CF. GNSA was able to support the proliferation of all 34 Gram-negative organisms examined, including 23 species most commonly associated with CF, but was unable to support the growth of the 12 Gram-positive or seven fungal organisms examined. Sensitivity studies demonstrated that the GNSA medium was able to detect not less than 1.50 x 102 CFU ml-1 sputum Pseudomonas aeruginosa, 2.38 x 102 CFU ml-1 sputum Burkholderia cepacia genomovar IIIb and 6.70 x 103 CFU ml-1 sputum Stenotrophomonas maltophilia. A comparison of the microbial flora detected in the sputa of 12 adult CF patients by employment of routine bacteriological agar media and GNSA, demonstrated that GNSA was able to detect all Gram-negative organisms cultured by routine media, but had the advantage of detecting Alcaligenes xylosoxidans in two CF patients, whom had no previous history of Gram-negative infection. CONCLUSIONS: GNSA was unable to support the proliferation of any Gram-positive organism or yeast/fungi, but was successful in supporting the growth of all Gram-negative organisms challenged. SIGNIFICANCE AND IMPACT OF THE STUDY: Employment of this medium coupled with semi-automated technology may aid in helping to efficiently determine Gram-negative loading of respiratory secretions, particularly in response to antibiotic intervention.

Adult↗
PubMed2000

Phosphorylation of c-Crk II on the negative regulatory Tyr222 mediates nerve growth factor-induced cell spreading and morphogenesis.

The Crk family of adaptor proteins participate in diverse signaling pathways that regulate growth factor-induced proliferation, anchorage-dependent DNA synthesis, and cytoskeletal reorganization, important for cell adhesion and motility. Using kidney epithelial 293T cells for transient co-transfection studies and the nerve growth factor (NGF)-responsive PC12 cell line as a model system for neuronal morphogenesis, we demonstrate that the non-receptor tyrosine kinase c-Abl is an intermediary for NGF-inducible c-Crk II phosphorylation on the negative regulatory Tyr(222). Transient expression of a c-Crk II Tyr(222) point mutant (c-Crk Y222F) in 293T cells induces hyperphosphorylation of paxillin on Tyr(31) and enhances complex formation between c-Crk Y222F and paxillin as well as c-Crk Y222F and c-Abl, suggesting that c-Crk II Tyr(222) phosphorylation induces both the dissociation of the Crk SH2 domain from paxillin and the Crk SH3 domain from c-Abl. Interestingly, examination of the early kinetics of NGF stimulation in PC12 cells showed that c-Crk II Tyr(222) phosphorylation preceded paxillin Tyr(31) phosphorylation, followed by a transient initial dissociation of the c-Crk II paxillin complex. PC12 cells overexpressing c-Crk Y222F manifested a defect in cellular adhesion and neuritogenesis that led to detachment of cells from the extracellular matrix, thus demonstrating the biological significance of c-Crk II tyrosine phosphorylation in NGF-dependent morphogenesis. Whereas previous studies have shown that Crk SH2 binding to paxillin is critical for cell adhesion and migration, our data show that the phosphorylation cycle of c-Crk II determines its dynamic interaction with paxillin, thereby regulating turnover of multiprotein complexes, a critical aspect of cytoskeletal plasticity and actin dynamics.

Animals↗
PubMed2000

Pediatric office emergencies and emergency preparedness in a small rural state.

OBJECTIVE: Although the frequency of pediatric office medical emergencies has been investigated in a retrospective manner, there have been no prospective studies. We examined how often pediatricians in a small rural state encountered medical emergencies in the office setting. This study included an in-office educational program and the donation of resuscitation equipment to study participants. DESIGN AND INTERVENTION: Thirty-eight of the 40 active primary care pediatric practices in the state of Vermont participated in this study. Thirty-seven sites were surveyed retrospectively regarding office preparedness for emergencies and frequency of office emergencies. At each practice site, an educational session was provided and an office resuscitation kit was donated. Thirty-seven sites were followed prospectively for a 12-month period evaluating the incidence of office medical emergencies and the adequacy of the donated resuscitation kit. RESULTS: Three hundred twenty-seven individuals from 38 Vermont pediatric practice sites participated. Forty-nine percent had basic life support training and 26% had pediatric advanced life support training. Sixty-seven percent of practices had a plan for office medical emergencies. Forty-six percent of practices had called local emergency medical services providers to their offices in the past year. Emergency preparedness ranged from a high of 95% of sites with oxygen to a low of 27% of sites with intraosseous needles. The estimate of the frequency of medical emergencies was.9 (standard deviation =.8) per office in the previous 12 months. In the 12-month study, there were 28 medical emergencies reported, averaging.8 (standard deviation = 1.5) emergencies per office per year. Sixty-five percent of participating sites had no emergencies in the study. Of the emergencies reported, 75% were respiratory in origin. The donated resuscitation kits proved sufficient for all of the emergencies reported. CONCLUSIONS: Serious medical emergencies are rare events in the primary care pediatric office, occurring less than once per office per year. The most common emergency situations encountered are respiratory. All of the emergencies in this study were managed effectively using a simple and relatively inexpensive resuscitation kit. We provided an emergency preparedness program for pediatric practices in a small rural state.

Certification↗
PubMed1984

Prostaglandin formation in the isolated human ductus arteriosus, aorta, pulmonary and umbilical arteries.

The prostaglandins comprise a large family of substances that includes primary prostaglandins, prostacyclin and thromboxane, all of which exhibit some vascular activity. The activity of each prostaglandin may be species - and organ - dependent, and the type of prostaglandin produced in a tissue is often dependent on the presence of terminal enzyme systems in that tissue. The prostaglandin endoperoxide PGH2 serves as a common intermediate for the enzymatic production of prostaglandins, thromboxanes and prostacyclin. We have obtained information on the biosynthesis of these compounds by the human ductus arteriosus, aorta, pulmonary and umbilical arteries in vitro. Vascular tissue samples were obtained from two fetuses of 16 to 18 weeks of gestation, two newborns of 26 and 35 weeks of gestation and in nine term infants. The vascular tissue samples were incubated with [1-14C]-arachidonic acid and/or [1-14C]-prostaglandin endoperoxide (PGH2). The study demonstrates the formation of prostaglandins and prostacyclins from all the vascular tissues and the formation of thromboxanes from the umbilical artery. The study implies that the above vessels contain "prostaglandin synthetase" enzymes as early as 16 weeks of gestation.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Opportunistic pulmonary aspergillosis with chest wall invasion. Plain film and computed tomographic findings.

A 37-year-old man with leukemia had the unusual complication of pulmonary aspergillosis eroding through adjacent bone. We were able to demonstrate this on computed tomography (CT) and even on the plain chest film. Bone invasion by an adjacent pulmonary lesion is most often attributed to other organisms or causes. This case demonstrates that aspergillosis must be added to the differential diagnosis of this finding. Recognizing this can be important for the prompt, appropriate treatment of opportunistic infections in the immunocompromised host.

Adult↗
PubMed1981

Age changes in neuromuscular junction morphology and acetylcholine receptor distribution on rat skeletal muscle fibres.

1. Neuromuscular junctions in the sternomastoid muscles of female Lewis rats were examined in animals up to 917 d old. 2. The average number of myelinated branches of terminal axons entering a junction increased with age of the animal, up to 400 d. This change could be described by a simple kinetic model which assumed that there was no influence of age on the ability of motoneurones to produce or maintain terminal branches, but that axons could produce or maintain only a limited number of branches. 3. There was a change in the over-all junctional length with age, but there was a significant increase in the number of discrete regions of high ACh receptor density in junctions from older animals. 4. There was a gradual decrease in the number of ACh receptors per junction with age after about 500 d, and muscles from some rats older than 500 d had detectable numbers of extrajunctional ACh receptors. 5. The changes in the neuromuscular junction with increased age occurred gradually over adult life.

Acetylcholine↗
PubMed1977

The role of heparin on platelet retention by acrylonitrile co-polymer dialysis membranes.

The role of heparin on platelet--foreign surface interactions was examined by platelet retention studies on acrylonitrile--dimethylaminoethyl methacrylate (AN-DMAEMA) dialysis membranes both with and without the bonding of heparin onto their surfaces. Heparin bonding significantly reduced platelet retention. Heparin in solution (4 units/ml.) increased platelet retention when the surface of the membranes was modified by ethylene oxide but had no significant effect on the platelet-retaining properties of unmodified membranes. Studies using heparin 99mTc demonstrated that unmodified membranes took up heparin from solution whereas ethylene oxide-modified membranes had little such affinity. The heparin bonding process greatly increased the heparin uptake achieved by simple soaking in heparin solution, and the leaching rate was less than 1% at 70 hours. The results indicate that heparin has two antagonistic effects in this platelet-foreign surface interaction: it acts directly on platelets to increase adhesiveness while acting on the foreign surface to reduce platelet retention.

Acrylates↗
PubMed1976

Platelets, foreign surfaces, and heparin.

These studies clearly indicate that heparin has 2 antagonistic effects in this platelet-foreign surface interaction; it acts directly on platelets to increase retention, while acting on the foreign surface to reduce platelet retention, perhaps by competing for cationic sites. This study also suggests that it is unlikely that heparin bonding confers reduced surface thrombogenicity by virtue of the ability to leach off that surface and that further studies in heparin bonding or other surface modification should consider the antiplatelet effect which can easily be studied in vitro.

Blood Platelets↗