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Biomedical subjects

G J Snipes

Publications and source records attributed to G J Snipes.

44 records · Page 3Linked to original sources
PubMed1991

Sensorimotor neuropathy in hemophagocytosis syndrome.

Hemophagocytosis syndromes are uncommon disorders marked by generalized proliferation of benign histiocytes and multiple organ failure. A 24-year-old woman presented with a fulminant illness consisting of fever, hepatic insufficiency and anemia, followed by respiratory compromise, cardiomyopathy, and uremia. She developed a sensorimotor polyneuropathy, with normal cerebrospinal fluid findings. Sural nerve biopsy demonstrated mild to moderate axonopathy, with regeneration and occasional segmental demyelination/remyelination. The recent and old hemorrhages present in the perineurium, and the marked infiltration by foamy histiocytes (macrophages) distributed mostly in the subperineural space, were presumably responsible for the Wallerian degeneration. Documentation of histiocytes in peripheral nerves in hemophagocytosis syndrome has not previously been shown.

Adult↗
PubMed1991

Gliofibroma. Case report.

The case history of an infant with a large gliofibroma is presented. Gliofibromas are rare mixed glialmesenchymal tumors that have been poorly characterized. The computerized tomography appearance and a detailed light and electron microscopic description are presented, along with immunoperoxidase studies of this tumor. This case is compared with gliofibromas described elsewhere in the literature.

Brain Neoplasms↗
PubMed1988

Light-microscopic immunolocalization of the growth- and plasticity-associated protein GAP-43 in the developing rat brain.

Growth-associated protein-43 (GAP-43) is a developmentally regulated, fast-axonally transported phosphoprotein whose synthesis and transport are enhanced during periods of growth and synaptic terminal formation. GAP-43 is a substrate of protein kinase C and is identical to protein F1, a phosphoprotein which is regulated during long-term potentiation in the hippocampus. In order to characterize the cellular localization of GAP-43, we have raised a specific antiserum against it, and used this as a probe to show that GAP-43 is neuron-specific, and is localized to growing neuronal processes in developing rat brain, and to presynaptic terminals in both the peripheral and central nervous system. In the mature CNS, GAP-43 immunoreactivity is present in most neuropil areas, but is especially dense in the molecular layers of the cerebellum, neocortex, and the hippocampus, structures known to exhibit synaptic plasticity. Its localization, together with biochemical data concerning the dynamics of its synthesis and its identity as protein F1, suggest that GAP-43 may be involved in axon growth in the developing nervous system, and in some aspect of synaptic plasticity in the mature CNS. These data also suggest that axon growth and synaptic plasticity in the brain may be regulated by a common mechanism, both involving the protein kinase C-mediated phosphorylation of GAP-43.

Aging↗
PubMed1987

Evidence for the coidentification of GAP-43, a growth-associated protein, and F1, a plasticity-associated protein.

GAP-43 is a fast-axonally transported protein whose expression correlates with periods of axon growth both during development and during regeneration. Similarities in molecular weight (43-47 kDa), pI (4.3-4.5), and aberrant behavior in acrylamide gels suggested that GAP-43 might be related or identical to protein F1, a protein kinase C substrate that has been shown to undergo a change in phosphorylation state during long-term potentiation in the hippocampus. Here we show that GAP-43 and protein F1 comigrate by two-dimensional PAGE and that antiserum raised against GAP-43 specifically immunoprecipitates protein F1. More direct evidence that GAP-43 and protein F1 are identical proteins was obtained by performing S. aureus V8 protease digests of a mixture of purified 32P-labeled protein F1 and purified GAP-43. Under these conditions, 2 phosphorylated peptide fragments of protein F1 corresponded exactly to 2 Coomassie-stainable bands from purified GAP-43. We conclude on the basis of these data that GAP-43 and protein F1 are identical proteins. Using light-microscopic immunocytochemistry, we also show that GAP-43/protein F1 immunoreactivity is localized to neuropil areas of the hippocampus consistent with its roles as a protein kinase C substrate in vivo and in long-term potentiation. These findings suggest that nerve growth during development and regeneration, and synaptic plasticity in the adult mammalian brain, may be mediated by a common mechanism involving the phosphorylation of GAP-43/protein F1.

Animals↗
PubMed1986

A protein induced during nerve growth (GAP-43) is a major component of growth-cone membranes.

Growth cones are specialized structures that form the distal tips of growing axons. During both normal development of the nervous system and regeneration of injured nerves, growth cones are essential for elongation and guidance of growing axons. Developmental and regenerative axon growth is frequently accompanied by elevated synthesis of a protein designated GAP-43. GAP-43 has now been found to be a major component of growth-cone membranes in developing rat brains. Relative to total protein, GAP-43 is approximately 12 times as abundant in growth-cone membranes as in synaptic membranes from adult brains. Immunohistochemical localization of GAP-43 in frozen sections of developing brain indicates that the protein is specifically associated with neuropil areas containing growth cones and immature synaptic terminals. The results support the proposal that GAP-43 plays a role in axon growth.

Aging↗
PubMed1986

Nerve injury stimulates the secretion of apolipoprotein E by nonneuronal cells.

Nerve trauma initiates significant changes in the composition of proteins secreted by nonneuronal cells. The most prominent of these proteins is a 37-kDa protein, whose expression correlates with the time course of nerve development, degeneration, and regeneration. We now report that the 37-kDa protein is apolipoprotein E (apoE). We produced a specific antiserum against the 37-kDa protein isolated from previously crushed nerves. This antiserum recognizes a 36-kDa protein in rat serum that we have purified and identified as apoE. The anti-37-kDa antiserum also recognizes apoE on electrophoretic transfer blots of authentic samples of high and very low density lipoproteins. The nerve 37-kDa protein comigrates with apoE by two-dimensional electrophoresis, shares a similar amino acid composition, and reacts with an antiserum against authentic apoE. The purified apoE specifically blocks the immunoprecipitation of [35S]methionine-labeled 37-kDa protein synthesized by nonneuronal cells. Thus, on the basis of its molecular mass, isoelectric point, amino acid composition, and immunological properties, we conclude that the 37-kDa protein is apoE. We also used light microscopic immunohistochemistry to localize apoE following nerve injury. In rats with optic nerve lesions, the 37-kDa antiserum bound specifically to the degenerating optic tracts and to the retino-recipient layers of the lateral geniculate nucleus and the superior colliculus. We propose that apoE is synthesized by phagocytic cells in response to nerve injury for the purpose of mobilizing lipids produced as a consequence of axon degeneration.

Amino Acids↗
PubMed1985

Steady growth cone currents revealed by a novel circularly vibrating probe: a possible mechanism underlying neurite growth.

The rate and direction of neurite growth have been shown in a number of studies to be determined by the distribution of adhesive sites on the growth cone. Recent evidence showing that the application of extrinsic electric fields can redistribute membrane molecules and alter both the rate and direction of neurite growth have raised the question whether endogenous electric fields might be produced by steady currents in growth cones. To investigate this question, we have devised a novel circularly vibrating microprobe capable of measuring current densities in the range of 5 nA/cm2 (near the theorectical limit of sensitivity), with a spatial resolution of 2 micron. The design of this device and the development of a novel algorithm for computing current vectors on-line is described. Using this probe we have found that cultured goldfish retinal ganglion cell growth cones generate steady inward currents at their tips. The measured currents, in the range of 10-100 nA/cm2, appear to flow into the filopodia at their tips and back outward near the junctures of the filopodia and the growth cone. The currents appear to be produced only during active growth. Ion substitution experiments support the conclusion that the majority of this current is carried by Ca2+ ions, which we postulate flow through a population of activated voltage-sensitive Ca2+ channels located on the filopodial tips. Calculation of the transmembrane current density (4 X 10(-6) nA/cm2) leads to an estimate of channel density (10 channels/micron2) in close agreement with the measured density of Ca2+ channels in other systems. The assumption that calcium channel proteins are conveyed to nerve terminals by active transport, whereas sodium channel proteins are conveyed passively by a slower somatofugal diffusion process [Strichartz et al, 1984], would explain why developing neurons tend to display Ca2+-sensitive electrogenesis at their growing tips, and Na+-sensitive action potentials later in development. In order to gain some insight into the possible role of these steady growth currents, we estimated the membrane depolarization and axial voltage gradient they produce. It is likely that the currents produce sufficient membrane depolarization (approximately equal to 4 mV) to cause autogenous activation of ion channel permeabilities. Similarly, the axial voltage gradient (approximately equal to 4 mV/cm) would be expected to move intracytoplasmic vesicles by electrophoresis at a rate (20-40 microns/hr) very close to that at which the filopodia are observed to grow.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗