Ceruloplasmin regulates iron levels in the CNS and prevents free radical injury.

Ceruloplasmin is a ferroxidase that oxidizes toxic ferrous iron to its nontoxic ferric form. We have previously reported that a glycosylphosphatidylinositol-anchored form of ceruloplasmin is expressed in the mammalian CNS. To better understand the role of ceruloplasmin in iron homeostasis in the CNS, we generated a ceruloplasmin gene-deficient (Cp(-/-)) mouse.

Modulation of JNK and p38 stress activated protein kinases in isolated islets of Langerhans: insulin as an autocrine survival signal.

Objective: The objective of this study was to determine the effects of islet isolation and cytokine exposure on e-JUN NH2 terminal kinase (JNK) and p38 activation and whether insulin or the p38 inhibitor PD169316 could modify the response.

Summary Background Data: Islet transplantation exposes the cells of the graft to a variety of stressful stimuli that could promote beta-cell death and lead to graft failure.

Methods: Islets from canine (n = 12) and cadaveric human (n = 6) pancreata were isolated and purified.

Predictors of physical outcomes in pediatric bone marrow transplantation.

The purpose of the present study was to investigate the hypothesis that family factors, in conjunction with clinical factors, are associated with physical outcomes in pediatric BMT. A prospective study of 68 pediatric patients (mean age = 7.5 years; ranging from 4 months to 18 years) undergoing BMT was carried out over a 6.

Alternative RNA splicing generates a glycosylphosphatidylinositol-anchored form of ceruloplasmin in mammalian brain.

Ceruloplasmin is a copper-containing ferroxidase that is essential for normal iron homeostasis. Whereas ceruloplasmin in plasma is produced and secreted by hepatocytes, in the brain a glycosylphosphatidylinositol (GPI)-anchored form of ceruloplasmin is expressed on the surface of astrocytes. By using a cDNA cloning approach, we have now determined that the GPI-anchored form of ceruloplasmin is generated by alternative RNA splicing.

A therapeutic vaccine approach to stimulate axon regeneration in the adult mammalian spinal cord.

Axon growth inhibitors associated with myelin play an important role in the failure of axon regeneration in the adult mammalian central nervous system (CNS). Several inhibitors are present in the mature CNS. We now present a novel therapeutic vaccine approach in which the animals' own immune system is stimulated to produce polyclonal antibodies that block myelin-associated inhibitors without producing any detrimental cellular inflammatory responses.

Prolonged delivery of brain-derived neurotrophic factor by adenovirus-infected Müller cells temporarily rescues injured retinal ganglion cells.

In this study, we demonstrate that: (i) injection of an adenovirus (Ad) vector containing the brain-derived neurotrophic factor (BDNF) gene (Ad.BDNF) into the vitreous chamber of adult rats results in selective transgene expression by Müller cells; (ii) in vitro, Müller cells infected with Ad.BDNF secrete BDNF that enhances neuronal survival; (iii) in vivo, Ad-mediated expression of functional BDNF by Müller cells, temporarily extends the survival of axotomized retinal ganglion cells (RGCs); 16 days after axotomy, injured retinas treated with Ad.

Axonal and nonneuronal cell responses to spinal cord injury in mice lacking glial fibrillary acidic protein.

We have examined the regeneration of corticospinal tract fibers and expression of various extracellular matrix (ECM) molecules and intermediate filaments [vimentin and glial fibrillary acidic protein (GFAP)] after dorsal hemisection of the spinal cord of adult GFAP-null and wild-type littermate control mice. The expression of these molecules was also examined in the uninjured spinal cord. There was no increase in axon sprouting or long distance regeneration in GFAP-/- mice compared to the wild type.

A novel glycosylphosphatidylinositol-anchored form of ceruloplasmin is expressed by mammalian astrocytes.

Ceruloplasmin is a copper-binding protein, which is the major ferroxidase in plasma of hepatic origin. We now provide evidence for a novel membrane-bound form of ceruloplasmin expressed by astrocytes in the mammalian central nervous system. Using a monoclonal antibody (1A1), we show that the cell surface antigen recognized by this antibody is ceruloplasmin and that it is directly anchored to the cell surface via a glycosylphosphatidylinositol (GPI) anchor.