PubMed Health⌕ Search

Biomedical subjects

J Courtney

Publications and source records attributed to J Courtney.

10 recordsLinked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗