Role of integrin-linked kinase in nerve growth factor-stimulated neurite outgrowth.

The role of integrin-linked kinase (ILK), a kinase that is involved in various cellular processes, including adhesion and migration, has not been studied in primary neurons. Using mRNA dot blot and Western blot analysis of ILK in rat and human brain tissue, we found that ILK is expressed in various regions of the CNS. Immunohistochemical and immunocytochemical techniques revealed granular ILK staining that is enriched in neurons and colocalizes with the beta1 integrin subunit. The role of ILK in neurite growth promotion by NGF was studied in rat pheochromocytoma cells and dorsal root ganglion neurons using a pharmacological inhibitor of ILK (KP-392) or after overexpression of dominant-negative ILK (ILK-DN). Both molecular and pharmacological inhibition of ILK activity significantly reduced NGF-induced neurite outgrowth. Survival assays indicate that KP-392-induced suppression of neurite outgrowth occurred in the absence of cell death. ILK kinase activity was stimulated by NGF. NGF-mediated stimulation of phosphorylation of both AKT and the Tau kinase glycogen synthase kinase-3 (GSK-3) was inhibited in the presence of KP-392 and after overexpression of ILK-DN. Consequently, ILK inhibition resulted in an increase in the hyperphosphorylation of Tau, a substrate of GSK-3. Together these findings indicate that ILK is an important effector in NGF-mediated neurite outgrowth.

Gradients and growth cone guidance of grasshopper neurons.

The generation of a functional nervous system is dependent on precise pathfinding of axons during development. This pathfinding is directed by the distribution of local and long-range guidance cues, the latter of which are believed to be distributed in gradients. Gradients of guidance cues have been associated with growth cone function for over a hundred years. However, little is known about the mechanisms used by growth cones to respond to these gradients, in part owing to the lack of identifiable gradients in vivo. In the developing grasshopper limb, two gradients of the semaphorin Sema-2a are necessary for correct neuronal pathfinding in vivo. The gradients are found in regions where growth cones make critical steering decisions. Observations of different growth cone behaviors associated with these gradients have provided some insights into how growth cones respond to them. Growth cones appear to respond more faithfully to changes in concentration, rather than absolute levels, of Sema-2a expression, whereas the absolute levels may regulate growth cone size.

Causes of readmission after operation for congenital heart disease.

BACKGROUND: Readmission after operations for congenital heart conditions has significant implications for patient care. Readmission rates vary between 8.7% and 15%. The aim of this study was to determine the incidence, causes, and risk factors associated with readmission. METHODS: 811 consecutive patients undergoing operations for congenital heart conditions were analyzed. Readmission was defined as admission to any hospital within 30 days of discharge for any cause. Demographic, preoperative, operative, and postoperative variables were evaluated. Univariate comparisons were made between the nonreadmission and readmission groups, and multivariate logistic regression analysis was made to determine independent risk factors for readmission. RESULTS: There were a total of 92 readmissions in 79 patients (9.7%). The reasons included cardiac (36, 39%), pulmonary (20, 22%), gastrointestinal (13, 14%), infectious (20, 22%), and other adverse events (2, 2%). Patients with either single-ventricle palliation or nasogastric feeding accounted for 40 (50%) readmissions. On univariate analysis, there were significant differences between readmitted and nonreadmitted patients in relation to patient age, chromosomal abnormality, mortality risk score, duration of mechanical ventilation, postoperative length of stay, single-ventricle physiology, and nasogastric feeding at discharge (p < 0.05). On multivariate analysis, significant risk factors for readmission were single-ventricle physiology (odds ratio [OR] 2.39; 95% confidence interval [CI] 1.28 to 4.47; p=0.005), preoperative arrhythmia (OR 2.59; 95% CI 1.02 to 6.59; p=0.04), longer postoperative length of stay (OR 2.2; 95% CI 1.22 to 3.99; p=0.008), and nasogastric tube feeding at discharge (OR 2.2; 95% CI 1.15 to 4.19; p=0.01). CONCLUSIONS: The incidence of readmission after operations for congenital cardiac conditions remains high. Efforts focusing on patients with single-ventricle palliation and those with preoperative arrhythmia, prolonged postoperative length of stay and nasogastric tube feeding at discharge may be particularly beneficial.