Fibulin-1 suppression of fibronectin-regulated cell adhesion and motility.

Fibulin-1 is an extracellular matrix protein often associated with fibronectin (FN) in vivo. In this study, the ability of fibulin-1 to modulate adhesion, spreading and motility-promoting activities of FN was investigated. Fibulin-1 was found to have pronounced inhibitory effects on the cell attachment and spreading promoted by FN. Fibulin-1 was also found to inhibit the motility of a variety of cell types on FN substrata. For example, the FN-dependent haptotactic motility of breast carcinoma (MDA MB231) cells, epidermal carcinoma (A431), melanoma (A375 SM), rat pulmonary aortic smooth muscle cells (PAC1) and Chinese hamster ovary (CHO) cells was inhibited by the presence of fibulin-1 bound to FN-coated Boyden chamber membranes. Cells transfected to overproduce fibulin-1 displayed reduced velocity, distance of movement and persistence time on FN substrata. Similarly, the incorporation of fibulin-1 into FN-containing type I collagen gels inhibited the invasion of endocardial cushion mesenchymal cells migrating from cultured embryonic heart explants. By contrast, incorporation of fibulin-1 into collagen gels lacking FN had no effect on the migration of endocardial cushion cells. These results suggest that the motility-suppressive effects of fibulin-1 might be FN specific. Furthermore, such effects are cell-type specific, in that the migration of gingival fibroblasts and endothelial cells on FN substrata is not responsive to fibulin-1. Additional studies found that the mechanism for the motility-suppressive effects of fibulin-1 does not involve perturbations of interactions between alpha5beta1 or alpha4 integrins, or heparan sulfate proteoglycans with FN. However, fibulin-1 was found to inhibit extracellular signal regulated kinase (ERK) activation and to suppress phosphorylation of myosin heavy chain. This ability to influence signal transduction cascades that modulate the actin-myosin motor complex might be the basis for the effects of fibulin-1 on adhesion and motility.

Detection and evaluation of asymptomatic myocarditis in schoolchildren: report of four cases.

STUDY OBJECTIVE: Data on the prevalence of myocarditis in children are limited. Autopsy studies have shown that myocarditis is often undiagnosed. We attempted to investigate the clinical features of asymptomatic myocarditis in four schoolchildren detected during a mass ECG screening in schoolchildren. DESIGN AND SETTING: To evaluate asymptomatic myocarditis, we clinically examined 12 schoolchildren who were referred to Shiga University of Medical Science Hospital, Otsu, Japan, because of abnormal ST or T waves detected during ECG screening. None of the 12 children had experienced any episodes suggesting cardiac disease or Kawasaki disease. Cardiac function and myocardial viability were assessed by two-dimensional echocardiography (2-DE), thallium-201 (201Tl) myocardial scintigraphy, and cardiac catheterization. Endomyocardial biopsy specimens were examined histologically. PATIENTS: Endomyocardial biopsy specimens revealed histologic evidence of myocarditis in 4 of the 12 children with abnormal ST or T waves. RESULTS: Abnormal tracer perfusion was observed on 201Tl myocardial scintigrams in these four children, but the results of coronary arteriography were normal. 2-DE showed left ventricular hypokinesis in one child and left ventricular enlargement in one of the four children with histologic evidence of myocarditis. A second endomyocardial biopsy specimen was obtained in two of four children, showing persistent myocarditis in one child. CONCLUSIONS: This type of screening program and indepth evaluation using 2-DE and 201Tl myocardial scintigraphy appear to be helpful in identifying children with myocarditis. The present histologic investigations suggested that even asymptomatic myocarditis might result in persistent heart damage.

Immunolocalization of vinculin in the heart of the early developing rat embryo.

BACKGROUND: The interaction of cells and extracellular matrix (ECM) components is important in the morphogenesis of the developing heart and is thought be mediated in part by adhesion plaques associated with vinculin, paxillin, talin, integrin, and other proteins. We investigated the patterns of expression of vinculin in the early embryonic rat heart to evaluate the role of vinculin in cardiac morphogenesis. METHODS: Vinculin expression was studied immunohistochemically in developing Sprague-Dawley embryonic rat hearts between days 11.5 and 15.5. RESULTS: Vinculin expression was transient and specific in the aorticopulmonary septum on day 13.5 and in the conal septum on day 14.5, when the respective septations were complete. Less vinculin immunoreactivity was detected in the atrioventricular cushion or ventricular septum, where obvious morphological alteration takes place. CONCLUSIONS: Sites that were immunoreactive for vinculin in the present study are reportedly associated with the distribution of neural cell adhesion molecules (N-CAM) or of soluble tropoelastin. Thus vinculin appears to play a key role in aorticopulmonary septation, where neural crest cells are transformed into ectomesenchyme. Vinculin appears to be involved in elastogenesis and is contributed by ectomesenchyme derived from the neural crest cells.

Case of Williams elfin facies syndrome with pulmonary artery sling.

We report the presence of pulmonary artery sling in a 4-year-old girl with the Williams elfin facies syndrome. A history of heavy and persistent wheezing during the first few months of life, associated with the current presentation of heart murmur and pulmonary stenosis, led us to investigate the presence of pulmonary artery sling. Both pulmonary artery sling and cardiovascular anomalies in Williams elfin facies syndrome have previously been linked to developmental anomalies of the 6th aortic arch. This appears to be the second reported case of this rare combination of anomalies.