Analyses of the differentiation potential of satellite cells from <Emphasis Type="Italic">myoD</Emphasis><Superscript>-/-</Superscript>, <Emphasis Type="Italic">mdx</Emphasis>, and <Emphasis Type="Italic">PMP22</Emphasis> C22 mice

Background  

Sporadic and sometimes contradictory studies have indicated changes in satellite cell behaviour associated with the progressive nature of human Duchenne muscular dystrophy (DMD). Satellite cell proliferation and number are reportedly altered in DMD and the mdx mouse model. We recently found that satellite cells in MSVski transgenic mice, a muscle hypertrophy model showing progressive muscle degeneration, display a severe ageing-related differentiation defect in vitro. We tested the hypothesis that similar changes contribute to the gradual loss of muscle function with age in mdx and PMP22 mice, a model of human motor and sensory neuropathy type 1A (HMSN1A).     

Urokinase-mediated thrombolysis: a dose-response relationship in cats. Work in progress.

A cat model was developed to study thrombolytic agents. The infrarenal aorta was surgically exposed, all side branches were ligated, and both ends of the segment were occluded. After preformed clot was injected into the segment, proximal flow was restored and a distal stenosis was created. Urokinase was infused at rates varying from 4,000 to 250,000 U/h. Amount of remaining clot was quantified every 15 minutes with cine angiography. Pre- and postinfusion measurements of prothrombin time, partial thromboplastin time, thrombin time, and levels of fibrinogen and fibrin degradation products were obtained. A graph of thrombolysis rate versus infusion rate was obtained yielding maximal thrombolytic activity at 126,000 U/h and 90% of maximal activity at an infusion rate of 70,000 U/h. Levels of fibrin degradation products did not change. Prothrombin, partial thromboplastin, and thrombin times increased with increasing infusion rates, leveling off at 100,000 U/h, while fibrinogen levels decreased, with a plateau at 50,000 U/h.     

The biocompatibility of compressed collagen foam plugs

The tissue reaction to reexpanded, purified bovine collagen sponge placed percutaneously into the lung, pleural space, liver, kidney, and muscle was studied in dogs and rabbits. In addition, the biocompatibility and radiopacity of tantalumtreated collagen foam plugs was examined. No adverse effects were found. We believe that collagen plugs may be of use in occluding needle tracts from biopsy sites to prevent complications such as bleeding or pneumothoraces.     

Mechanical clot dissolution: new concept

The authors present preliminary data on in vitro mechanical clot dissolution by means of a catheter with a tiny high-speed propeller enclosed in a special housing. Preweighed human blood clots were subjected to the catheter in a test tube with saline at various propeller speeds and durations of application. After filtration of the resultant slurry, the clot residue was weighed and examined histologically. Clot dissolution was found to be related to both the duration and speed of propeller rotation. No fibrin residue was seen after dissolution, although potential embolic material, composed of clumps of cellular debris as large as 208 microns in longest dimension, was found. Mechanical clot dissolution could possibly be used in any natural or synthetic blood vessel in which there is acute or subacute thrombosis, with fewer complications and lower cost than obtained with traditional methods.     

The inferior vena cava clip. The percutaneous approach

Pulmonary embolism in high-risk patients may be minimized by surgical inferior vena cava (IVC) clipping or by the insertion of caval filters. A percutaneous clipping technique was developed that narrows the cava while allowing caval patency. The caval clip is inserted through a percutaneous translumbar approach under fluoroscopic control. Nine dogs underwent percutaneous translumbar caval clip placement without complications. Three of four dogs, followed-up for 5 to 19 weeks by angiography and caval pressure measurements, showed caval patency. This technique eliminates the risks of surgical IVC clip placement and risks from the insertion of intravascular foreign bodies such as filters.     

Wnt signaling promotes AChR aggregation at the neuromuscular synapse in collaboration with agrin

Wnt proteins regulate the formation of central synapses by stimulating synaptic assembly, but their role at the vertebrate neuromuscular junction (NMJ) is unclear. Wnt3 is expressed by lateral motoneurons of the spinal cord during the period of motoneuron-muscle innervation. Using gain- and loss-of-function studies in the chick wing, we demonstrate that Wnt signaling is necessary for the formation of acetylcholine receptor (AChR) clusters without affecting muscle growth. Similarly, diaphragms from Dishevelled-1 mutant mice with deficiency in Wnt signaling exhibit defects in cluster distribution. In cultured myotubes, Wnt3 increases the number and size of AChR clusters induced by agrin, a nerve-derived signal critical for NMJ development. Wnt3 does not signal through the canonical Wnt pathway to induce cluster formation. Instead, Wnt3 induces the rapid formation of unstable AChR micro-clusters through activation of Rac1, which aggregate into large clusters only in the presence of agrin. Our data reveal a role for Wnts in post-synaptic assembly at the vertebrate NMJ by enhancing agrin function through Rac1 activation.