Inclusion of Exercise Prescription in Solid Organ Transplant in Physical Therapy Curricula Across Canadian Universities: A National Survey.

This study evaluated the extent of education about exercise prescription for patients with solid organ transplant (SOT) provided in physical therapy (PT) entry-level programmes across Canadian universities. The nature (content being taught), delivery (modes used to disseminate information), time dedicated to the topic, and opinions of educators were explored. A cross-sectional survey was emailed to 36 educators at Canadian universities.

Perfluorocarbon Labeling of Human Glial-Restricted Progenitors for F Magnetic Resonance Imaging.

One of the fundamental limitations in assessing potential efficacy in Central Nervous System (CNS) transplantation of stem cells is the capacity for monitoring cell survival and migration noninvasively and longitudinally. Human glial-restricted progenitor (hGRP) cells (Q-Cells) have been investigated for their utility in providing neuroprotection following transplantation into models of amyotrophic lateral sclerosis (ALS) and have been granted a Food and Drug Administration (FDA) Investigational New Drug (IND) for intraspinal transplantation in ALS patients. Furthermore, clinical development of these cells for therapeutic use will rely on the ability to track the cells using noninvasive imaging methodologies as well as the verification that the transplanted GRPs have disease-relevant activity.

Transplanted human glial-restricted progenitors can rescue the survival of dysmyelinated mice independent of the production of mature, compact myelin.

The therapeutic effect of glial progenitor transplantation in diseases of dysmyelination is currently attributed to the formation of new myelin. Using magnetic resonance imaging (MRI), we show that the therapeutic outcome in dysmyelinated shiverer mice is dependent on the extent of cell migration but not the presence of mature and compact myelin. Human or mouse glial restricted progenitors (GRPs) were transplanted into rag2 shiverer mouse neonates and followed for over one year.

Human glial progenitor engraftment and gene expression is independent of the ALS environment.

Although Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease, basic research studies have highlighted that astrocytes contribute to the disease process. Therefore, strategies which replace the diseased astrocyte population with healthy astrocytes may protect against motor neuron degeneration. Our studies have sought to evaluate astrocyte replacement using glial-restricted progenitors (GRPs), which are lineage-restricted precursors capable of differentiating into astrocytes after transplantation.

ICV-transplanted human glial precursor cells are short-lived yet exert immunomodulatory effects in mice with EAE.

Human glial precursor cells (hGPs) have potential for remyelinating lesions and are an attractive cell source for cell therapy of multiple sclerosis (MS). To investigate whether transplanted hGPs can affect the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, we evaluated the therapeutic effects of transplanted hGPs together with the in vivo fate of these cells using magnetic resonance imaging (MRI) and bioluminescence imaging (BLI). At 14 days post-EAE induction, mice (n = 19) were intracerebroventricularly (ICV) injected with 5 × 10(5) hGPs that were magnetically labeled with superparamagnetic iron oxide (SPIO) particles as MR contrast agent and transduced with firefly luciferase for BLI of cell survival.

Human glial-restricted progenitor transplantation into cervical spinal cord of the SOD1 mouse model of ALS.

Cellular abnormalities are not limited to motor neurons in amyotrophic lateral sclerosis (ALS). There are numerous observations of astrocyte dysfunction in both humans with ALS and in SOD1(G93A) rodents, a widely studied ALS model. The present study therapeutically targeted astrocyte replacement in this model via transplantation of human Glial-Restricted Progenitors (hGRPs), lineage-restricted progenitors derived from human fetal neural tissue.

Human glial-restricted progenitors survive, proliferate, and preserve electrophysiological function in rats with focal inflammatory spinal cord demyelination.

Transplantation of glial progenitor cells results in transplant-derived myelination and improved function in rodents with genetic dysmyelination or chemical demyelination. However, glial cell transplantation in adult CNS inflammatory demyelinating models has not been well studied. Here we transplanted human glial-restricted progenitor (hGRP) cells into the spinal cord of adult rats with inflammatory demyelination, and monitored cell fate in chemically immunosuppressed animals.

Transplantation of human glial restricted progenitors and derived astrocytes into a contusion model of spinal cord injury.

Transplantation of neural progenitors remains a promising therapeutic approach to spinal cord injury (SCI), but the anatomical and functional evaluation of their effects is complex, particularly when using human cells. We investigated the outcome of transplanting human glial-restricted progenitors (hGRP) and astrocytes derived from hGRP (hGDA) in spinal cord contusion with respect to cell fate and host response using athymic rats to circumvent xenograft immune issues. Nine days after injury hGRP, hGDA, or medium were injected into the lesion center and rostral and caudal to the lesion, followed by behavioral testing for 8 weeks.

Isolation, characterization and preclinical development of human glial-restricted progenitor cells for treatment of neurological disorders.

Aim: Glial-restricted progenitor cells (GRPs), a neural cell population that gives rise to astrocytes and oligodendrocytes both in vitro and in vivo, hold great promise as a cellular therapeutic for the treatment of demyelinating and neurodegenerative diseases of the CNS. The manufacturing and characterization protocols of human-derived GRPs (hGRPs; trade name Q-Cells) for use in a clinical setting that adhere to rigorous standards for their isolation, propagation, characterization and storage are presented.

Materials & Methods: hGRPs, defined by their immunoreactivity with A2B5 antibodies, were isolated from fetal cadaver forebrain tissue of mice 17-24 weeks gestational age using Miltenyi paramagnetic bead cell separation technology.

Postmyocardial infarction remodeling and coronary reserve: effects of ivabradine and beta blockade therapy.

We compared the effects of heart rate reduction (HRR) by the hyperpolarization-activated pacemaker current (I(f)) channel inhibitor ivabradine (MI+Iva) and the beta(1)-blocker atenolol (MI+Aten) on ventricular remodeling and perfusion after myocardial infarction (MI) in middle-aged (12 mo) Sprague-Dawley rats. Mean HRR was virtually identical in the two treated groups (19%). Four weeks after coronary artery ligation, maximal myocardial perfusion fell in the MI group but was preserved in infarcted rats treated with either Iva or Aten.

Expression profiling of human glial precursors.

Background: We have generated gene expression databases for human glial precursors, neuronal precursors, astrocyte precursors and neural stem cells and focused on comparing the profile of glial precursors with that of other populations.

Results: A total of 14 samples were analyzed. Each population, previously distinguished from each other by immunocytochemical analysis of cell surface markers, expressed genes related to their key differentiation pathways.

A new experimental model of glaucoma in rats through intracameral injections of hyaluronic acid.

An experimental model of pressure-induced optic nerve damage would greatly facilitate the understanding of the cellular events leading to ganglion cell death, and how they are influenced by intraocular pressure and other risk factors associated to glaucoma. The aim of the present report was to study the effect of a long-term increase of intraocular pressure in rats induced by intracameral injections of hyaluronic acid with respect to electroretinographic activity and retinal and optic nerve histology. For this purpose, hyaluronic acid was injected weekly in the rat anterior chamber of one eye, whereas the contralateral eye was injected with saline solution.

A role for the juxtamembrane domain of beta-dystroglycan in agrin-induced acetylcholine receptor clustering.

Synaptic differentiation results from an exchange of informational molecules between synaptic partners during development. At the vertebrate neuromuscular junction, agrin is one molecule presented by the presynaptic motor neuron that plays an instructive role in postsynaptic differentiation of the muscle cell, most notably in aggregation of acetylcholine receptors (AChRs). Although agrin is the best-characterized synaptogenic molecule, its mechanism of action remains uncertain, but clearly, it requires the receptor tyrosine kinase MuSK (muscle-specific kinase), the intracellular protein rapsyn, an Src-like kinase, and cytoskeletal components.

Effect of hyaluronic acid on intraocular pressure in rats.

Purpose: To study the effect of acute or chronic intracameral injection of hyaluronic acid on intraocular pressure (IOP) in rats.

Methods: Acute or chronic injections of hyaluronic acid were performed unilaterally in the rat eye's anterior chamber, whereas the contralateral eye was injected with saline solution. IOP was assessed daily or weekly by a tonometer in conscious rats.

Microcontact printing: a versatile technique for the study of synaptogenic molecules.

During synaptogenesis information exchanged locally between synaptic partners results in precise alignment of morphological and molecular specializations. For example, agrin derived from motoneurons induces localized postsynaptic differentiation at the neuromuscular synapse. Similar information molecules are thought to act at other synapses; however, techniques for directly evaluating synaptogenic activities of such molecules are lacking.

WW and EF hand domains of dystrophin-family proteins mediate dystroglycan binding.

The membrane-spanning dystrophin glycoprotein complex mediates an indirect linkage between the actin-based cytoskeleton and the extracellular matrix. Although expressed by diverse cell types, genetic lesions of members of this complex result in muscular dystrophy phenotypes emphasizing the importance of these interactions in muscle cells. We have characterized interactions between dystrophin family members and dystroglycan: cytoskeletal and transmembrane components of the complex, respectively.

Dynamic Interfacial Tension of Surfactant Mixtures at Liquid-Liquid Interfaces.

Dynamic interfacial tensions for surfactant mixtures at liquid-liquid interfaces were obtained with a drop volume tensiometer. The surfactants tested were Triton X-100, palmitic acid, and Span 80 at both the water-hexadecane and water-mineral oil interfaces. Two-surfactant mixtures were examined with the surfactants initially dissolved in different phases to minimize bulk-phase interactions.

Globular domains of agrin are functional units that collaborate to induce acetylcholine receptor clustering.

Agrin, an extracellular matrix protein involved in neuromuscular junction formation, directs clustering of postsynaptic molecules, including acetylcholine receptors (AChRs). This activity resides entirely in the C-terminal portion of the protein, which consists of three laminin-like globular domains (G-domains: G1, G2 and G3) and four EGF-like repeats. Additionally, alternate mRNA splicing yields G-domain variants G2(0,4) with 0- or 4-amino-acid inserts, and G3(0, 8,11,19) with 0-, 8-, 11- or 19-amino-acid inserts.

A functional role for specific spliced variants of the alpha7beta1 integrin in acetylcholine receptor clustering.

The clustering of acetylcholine receptors (AChR) on skeletal muscle fibers is an early event in the formation of neuromuscular junctions. Recent studies show that laminin as well as agrin can induce AChR clustering. Since the alpha7beta1 integrin is a major laminin receptor in skeletal muscle, we determined if this integrin participates in laminin and/or agrin-induced AChR clustering.

Effect of Neck Formation on the Measurement of Dynamic Interfacial Tension in a Drop Volume Tensiometer.

Dynamic interfacial tension values obtained by drop volume tensiometry will be affected under certain experimental conditions by the formation of a neck between the drop and the capillary tip. This phenomenon must be accounted for to obtain accurate values of interfacial tension. In this work, neck formation for a water-mineral oil system is studied under conditions where hydrodynamic effects can be neglected.

Agrin inhibits neurite outgrowth but promotes attachment of embryonic motor and sensory neurons.

Agrin is a secreted glycoprotein with the ability to cluster cell surface molecules, including the nicotinic acetylcholine receptor (AchR) on muscle cells. Alternate splicing of agrin mRNA results in a family of agrin proteins which differ in their clustering potency. Neuronal-specific isoforms with the highest clustering activity play a role in clustering postsynaptic proteins at the neuromuscular junction.

Alternative RNA splicing that determines agrin activity regulates binding to heparin and alpha-dystroglycan.

Agrin is a component of the extracellular matrix that regulates aspects of neuromuscular junction differentiation. Identification of agrin-binding proteins has lead to the suggestion that alpha-dystroglycan is a muscle cell surface proteoglycan that mediates agrin activity. To further test this hypothesis, we have compared the ability of differentially active agrin isoforms to interact with a model component of proteoglycans, heparin, as well as with the putative proteoglycan alpha-dystroglycan.