[Intestinal mycotic involvement: results of 10-day therapy with nystatin].
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Candida↗
Biomedical subjects
A Blesch
Publications and source records attributed to A Blesch.
Functional characterization of NGF-secreting cell grafts to the acutely injured spinal cord.
Previously we reported that grafts of cells genetically modified to produce human nerve growth factor (hNGF) promoted specific and robust sprouting of spinal sensory, motor, and noradrenergic axons. In the present study we extend these investigations to assess NGF effects on corticospinal motor axons and on functional outcomes after spinal cord injury. Fibroblasts from adult rats were transduced to express human NGF; control cells were not genetically modified. Fibroblasts were then grafted to sites of midthoracic spinal cord dorsal hemisection lesions. Three months later, recipients of NGF-secreting grafts showed deficits on conditioned locomotion over a wire mesh that did not differ in extent from control-lesioned animals. On histological examination, NGF-secreting grafts elicited specific sprouting from spinal primary sensory afferent axons, local motor axons, and putative cerulospinal axons as previously reported, but no specific responses from corticospinal axons. Axons responding to NGF robustly penetrated the grafts but did not exit the grafts to extend to normal innervation territories distal to grafts. Grafted cells continued to express NGF protein through the experimental period of the study. These findings indicate that 1) spinal cord axons show directionally sensitive growth responses to neurotrophic factors, 2) growth of axons responding to a neurotrophic factor beyond an injury site and back to their natural target regions will likely require delivery of concentration gradients of neurotrophic factors toward the target, 3) corticospinal axons do not grow toward a cellular source of NGF, and 4) functional impairments are not improved by strictly local sprouting response of nonmotor systems.
Acute Disease↗
Ex vivo gene therapy for Alzheimer's disease and spinal cord injury.
Gene transfer is a potential means of treating chronic neurologic disorders and injury related neural degeneration. One approach for transferring genes to the CNS is to genetically modify cells in vitro and then transplant the cells to the CNS. For example, fibroblasts can be infected with a replication-defective retrovirus expressing a transgene, and can then be transplanted into the brain or spinal cord, thereby providing neurotrophic factors and substrates for axonal growth and elongation. In this review we discuss the grafting of neurotrophic factor secreting autologous fibroblasts in the rat and primate CNS. NGF secreting grafts have been shown to prevent degeneration of cholinergic neurons in the basal forebrain of primates and to induce sprouting of sensory, motor, and noradrenergic neurites after spinal cord injury. These results suggest the potential usefulness of ex vivo gene transfer for the treatment of Alzheimer's disease and spinal cord injury.
Alzheimer Disease↗