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G K Bergey

Publications and source records attributed to G K Bergey.

At least 37 records · Page 2Linked to original sources
PubMed1994

Analysis of mesial temporal seizure onset and propagation using the directed transfer function method.

The directed transfer function (DTF) method, a multichannel parametric method of analysis based on an autoregressive model, is a newly developed tool that permits determination of patterns of flow of activity. The DTF method of analysis was applied to seizures originating from mesial temporal lobe structures in 3 patients recorded by combined subdural grid and depth electrode arrays. These first applications to human intracranial recordings demonstrated that the DTF method can accurately determine patterns of seizure onset and propagation. In addition the DTF method can provide evidence regarding patterns of flow of seizure activity that are not readily apparent from visual inspection of the EEG recordings. Important considerations for appropriate application of the DTF method for the analysis of intracranial ictal recordings are discussed.

Brain↗
PubMed1994

Cytokine-gene expression in measles-infected adult human glial cells.

The expression of interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF) alpha transcripts in cultured human glial cells was examined using reverse transcription followed by polymerase chain reaction (PCR) amplification and Southern blot quantitation. Microglial cultures derived from brain biopsy specimens from three different individuals expressed transcripts for the three cytokines under basal culture conditions. This expression was enhanced in response to measles virus (MV) infection (IL-1 beta, 2.2-8.8-fold; IL-6, 2.5-8.4-fold; TNF alpha, 2.2-3.2-fold). Neither IL-1 beta nor TNF alpha transcripts were detectable in undissociated brain tissue from two individuals, suggesting that the basal expression of these cytokines in culture may have been induced by tissue dissociation or by the culture conditions. Oligodendrocytes did not express cytokine transcripts under basal culture conditions, and IL-1 beta and IL-6 but not TNF alpha transcripts could be induced by MV. Similarly, meningeal fibroblasts expressed IL-1 beta and IL-6 but not TNF alpha in response to MV-infection, suggesting that the production of TNF alpha is more cell type-restricted than either IL-1 beta or IL-6. The results indicate that adult human microglia can participate in the inflammatory response to MV infection in the CNS by producing cytokines that contribute to inflammation and demyelination. In addition, besides their role in myelination, oligodendrocytes can potentially influence immunoreactivity in the CNS by producing IL-1 beta and IL-6.

Adolescent↗
PubMed1992

Human T-cell leukemia virus type I infection of monocytes and microglial cells in primary human cultures.

The pathogenesis of progressive spastic paraparesis [HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)], a serious consequence of human T-cell leukemia virus type I (HTLV-I) infection, is unclear. T and B lymphocytes can be naturally infected by HTLV-I, but the susceptibility to HTLV-I infection of other cell types that could contribute to the pathogenesis of HAM/TSP has not been determined. We found that a human monocyte cell line (THP-1), primary human peripheral blood monocytes, and isolated microglial cells but not astrocytes or oligodendroglial cells derived from adult human brain were infected by HTLV-I in vitro. Infection with HTLV-I enhanced the secretion of interleukin 6 in human microglial cell-enriched cultures but did not stimulate the release of interleukin 1 from monocytes or microglial cells. Tumor necrosis factor alpha production was stimulated by HTLV-I infection of monocytes and microglial cells and could be enhanced by suboptimal amounts of lipopolysaccharide. Since both tumor necrosis factor alpha and interleukin 6 have been implicated in inflammatory demyelination and gliosis, our findings suggest that human microglial cells and monocytes infected with and activated by HTLV-I could play a role in the pathogenesis of HAM/TSP.

Brain↗
PubMed1989

Proteolytic cleavage of tetanus toxin increases activity.

Tetanus toxin is initially synthesized in the form of a single polypeptide chain and then proteolytically "nicked" by the bacteria to produce a two-chain structure joined by a disulfide bond. This two-chain form of the toxin is the form known to be biologically active. Whether such nicking is necessary for activity, as it is for certain other bacterial toxins, has not been demonstrated previously. Single-chain toxin preparations produced by salt extraction from the bacteria are characterized and compared with pure two-chain toxin obtained from extracellular filtrates. The ability of these various toxin preparations to produce paroxysmal activity in mouse spinal cord neurons grown in dissociated cell culture is described. The pure two-chain toxin is demonstrated to have greater activity than the single-chain toxin preparations. Indeed the activity of the single-chain toxin preparations can be explained by the small amounts of residual two-chain toxin present in these extracts. Using a protease from a toxin-minus strain of Clostridium tetani to convert a single-chain toxin preparation to two-chain toxin increases toxin activity. In vivo the single-chain toxin preparation is also less toxic. These findings indicate that proteolytic nicking of tetanus toxin increases activity. The unnicked, single-chain form of tetanus toxin may be a relatively nontoxic protoxin form of the toxin; this is a structure-function relationship similar to that of other bacterial protein toxins.

Animals↗
PubMed1987

Differential effects of tetanus toxin on inhibitory and excitatory synaptic transmission in mammalian spinal cord neurons in culture: a presynaptic locus of action for tetanus toxin.

Tetanus toxin reduces monosynaptic inhibitory and excitatory synaptic transmission in mouse spinal cord neurons in culture. Inhibitory transmission is preferentially reduced by the toxin; however, excitatory transmission is also ultimately reduced and blocked by the concentrations of toxin used in these studies. Recordings from monosynaptically connected cell pairs revealed a marked diminution in amplitude of evoked monosynaptic inhibitory postsynaptic potentials coincident with the onset of convulsant action at a time when evoked monosynaptic EPSPs were relatively unaffected. Increased polysynaptic excitation occurred as a result of diminished inhibition. This supports the reduction of inhibition as an important mechanism in the convulsant action of tetanus toxin. Quantal analysis of the late effects of tetanus toxin on the monosynaptic excitatory postsynaptic potential revealed a reduction in quantal number with no reduction in quantal size, thus demonstrating a presynaptic locus of action for the toxin on spinal neurons.

Animals↗
PubMed1986

Tetanus toxin in dissociated spinal cord cultures: long-term characterization of form and action.

The clinical course of tetanus is notable, in addition to its often dramatic clinical presentation, by the long duration of the neuromuscular symptoms. Survivors may have tetanic manifestations for several weeks after the onset of the disease. In this article we correlate the duration of specific electrophysiologic effects produced by tetanus toxin with the degradation of cell-associated toxin in primary cultures of mouse spinal cord neurons. From these studies we can conclude that the toxin has a half-life of 5-6 days. Both the heavy and the light chains of tetanus toxin degrade at similar rates. Labeled toxin, visualized by radioautography, is associated with neuronal cell bodies and neurites, and its distribution is not altered during a 1-week period following toxin exposure. Blockade of synaptic activity persists for weeks at the concentration of radiolabeled toxin used in these studies. This blockade of transmission is reversed as the toxin is degraded, suggesting that degradation of toxin may be a sufficient mechanism for recovery from tetanus.

Action Potentials↗
PubMed1983

Tetanus toxin: convulsant action on mouse spinal cord neurons in culture.

The effects of direct application of tetanus toxin on fetal mouse spinal cord neurons in culture are described. Tetanus toxin produces increased excitation characterized by paroxysmal depolarizing events (PDE). In contrast to the abrupt onset of convulsant action produced by postsynaptic glycine antagonist strychnine, the convulsant action of tetanus occurs after a dose-dependent latent period. The onset of the convulsant action of tetanus toxin is paralleled by a reduction in observed spontaneous inhibitory synaptic potentials. Excitatory synaptic events can be identified as components of some tetanus-PDE. The toxin does not alter postsynaptic responses to the inhibitory amino acids glycine and gamma-aminobutyric acid. The latency and convulsant action of tetanus toxin are consistent with an irreversible presynaptic membrane interaction that reduces inhibitory transmission, a mechanism of action distinct from those of convulsants that antagonize inhibitory transmitters at the postsynaptic membrane.

Action Potentials↗
PubMed1981

Calcium-dependent action potentials in mouse spinal cord neurons in cell culture.

Following blockade of membrane potassium conductance with tetraethylammonium ions or 3-aminopyridine, long-duration action potentials were recorded from mouse spinal cord neurons in primary dissociated cell culture. The action potentials were calcium-dependent since they: (1) were not blocked by the sodium-channel blocker tetrodotoxin, (2) could be recorded in sodium-free, calcium-containing medium (3) could not be evoked in sodium-containing, calcium-free medium, (4) were blocked by calcium channel blockers manganese and cobalt and (5) had overshoot amplitudes that varied linearly with the log of the extracellular calcium concentration (slope of 27.5 mV/decade change in calcium concentration).

Action Potentials↗
PubMed1981

Neuronal maturation in mammalian cell culture is dependent on spontaneous electrical activity.

Fetal mouse spinal cord (SC) and dorsal root ganglion (DRG) neurons undergo a process of maturation in cell culture lasting a month or more. We have investigated the role of electrical activity in this maturational process with the use of tetrodotoxin (TTX), the specific blocker of the voltage-sensitive sodium channel responsible for action potential generation. This agent completely eliminates the spikes and related synaptic activity which occur abundantly in untreated cultures. Such blockade of electrical activity in the cultures, when begun early (day 1 or day 8 in vitro), results in a 85-95% reduction in the number of large SC neurons, without affecting DRG neuron numbers. TTX treatment initiated when cultures are mature (day 70) has no significant effect on either DRG or SC neurons. Intermediate effects are obtained when treatment is initiated at day 35 in vitro. The activity of the nerve-specific enzyme choline acetyltransferase, is significantly decreased by early TTX treatment, while DNA and protein content of the cultures (primarily contributed by glial and fibroblastic cells) is not affected.

Animals↗
PubMed1981

Adverse effects of phenobarbital on morphological and biochemical development of fetal mouse spinal cord neurons in culture.

The effects of chronic phenobarbital treatment on neuronal development were assessed in cell cultures of fetal rodent spinal cord. The activity of the principal enzyme involved in acetylcholine synthesis, choline acetyltransferase (CAT), and counts of large spinal cord neurons were used as indicators of neuronal development Phenobarbital (30 to 120 micrograms/ml) added to cultures for two- or six-week periods produced dose-dependent decreases in both CAT activity and neurons counts. Barbituric acid at doses equimolar to those at which phenobarbital produced these decreases had no effect.

Acetylcholine↗
PubMed1980

Effects of D,L-alpha-aminoadipate on postsynaptic amino acid responses in cultured mouse spinal cord neurons.

The effects of the dicarboxylic amino acid, DL-alpha-aminoadipate (DLAA) on amino acid responses have been investigated using intracellular recordings from mouse spinal cord neurons grown in dissociated cell culture. DL-alpha-Aminoadipate markedly antagonized postsynaptic responses to iontophoretically appllied aspartate; antagonism of glutamate was much less prominent. DL-alpha-Aminoadipate altered the affinity of aspartate for its receptor while having no observed effects on aspartate-receptor cooperativity. No direct effects of DLAA on membrane potentials or passive membrane properties were seen at the currents used for antagonism. Responses to the inhibitory amino acids GABA and glycine were unaffected by DLAA.

2-Aminoadipic Acid↗
PubMed1980

Cell interactions in nerve and muscle cell cultures.

The neurotransmitter synthesized by a given class of neurones is subject to modification and, indeed, a qualitative switchover in transmitter biochemistry recently has been demonstrated (Furshpan, POtter & Landis, 1980; Walicke, Campenot & Patterson, 1977). In conjunction with the specification of transmitter biosynthesis that becomes established in a given neurone, a complementary specification of appropriate receptor production is required in any cell functionally post-synaptic to that neurone. An additional requirement of peculiar force in the nervous system has to do with the spatial organization of the receptors in the surface membrane of the post-synaptic cell once the receptors are synthesized. Inappropriately distributed receptors are useless receptors. The perfect registration of a variety of types of presynaptic release sites with high post-synaptic concentrations of appropriate receptors constitutes one of the outstanding features of nervous-system organization that must be accounted for. We report some experiments directed toward understanding the cell biology of regulation of receptor distribution over the surface membrane of muscle cells. Functional synaptic connexions are formed quite early in development and the stability and maturation of synaptic networks is contingent on a number of factors. One interesting contingency is that related to the functional activity of developing networks. Do only those networks survive and mature which are activated by stimuli impinging from the environment? (Wiesel & Hubel, 1963). Put more simple, are action potentials and synaptic activity essential for neuronal maturation? We address this question in cell culture systems from the mammalian central nervous system.

Animals↗