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Biomedical subjects

W A Wilson

Publications and source records attributed to W A Wilson.

At least 109 records · Page 6Linked to original sources
PubMed1989

Cyclophosphamide use in a young woman with antiphospholipid antibodies and recurrent cerebrovascular accident.

We have described a 25-year-old woman with recurrent cerebral thrombosis associated with very high levels of antibodies against phospholipids. Antinuclear antibodies and clinical features of a defined connective tissue disease were absent. Treatment with plasmapheresis, prednisone, intravenous cyclophosphamide, and warfarin was accompanied by disappearance from the serum of the lupus anticoagulant and the biologic false-positive test for syphilis; IgG anticardiolipin antibodies persisted, however, and the patient had a second cerebral thrombosis. Clinical improvement ultimately occurred after the dosage of cyclophosphamide was optimized and the level of IgG anticardiolipin antibody decreased to a level lower than any that has been previously associated with thrombotic complications.

Adult↗
PubMed1989

C4 concentrations and C4 deficiency alleles in systemic lupus erythematosus.

In a study of 66 patients with systemic lupus erythematosus (SLE) and 80 controls it was found that the presence of two deficiency (null) alleles of C4 had a significant effect on mean C4 concentrations in serum. In six controls who each had two C4 null alleles the mean C4 concentration in serum was 56% lower than in 43 controls without C4 null alleles; the nadir of the C4 concentration in four patients with SLE with two null alleles was also lower by a mean of 55% than in 32 patients who did not have null alleles. Reduced production of C4 allotypes in subjects with two null alleles may be an important determinant of total C4 concentration in patients with SLE. For optimal interpretation of C4 concentrations in SLE, C4 allotyping appears to be indicated, particularly to identify patients who have two null alleles of C4.

Adult↗
PubMed1989

Baclofen has a proepileptic effect in the rat dentate gyrus.

Effects of the gamma-aminobutyric acidB (GABAB) agonist baclofen on evoked responses and recurrent inhibition in the dentate gyrus were examined in rat hippocampal slices. Granule cell firing was induced by perforant path stimulation; recurrent inhibition was induced by pairing the perforant path stimulus with a preceding mossy fiber stimulus and was mediated through GABAA receptors. Whereas (+/-)-baclofen (10 microM) suppressed the perforant path-evoked population spike only about 20%, it suppressed recurrent inhibition about 84% and converted the perforant path-evoked response to an epileptiform response with multiple population spikes. These effects were concentration-dependent (estimated EC50 values for (+/-)-baclofen were 0.6 microM for suppression of recurrent inhibition and 1.0 microM for induction of multiple population spikes) and stereoselective for (-)-baclofen. Baclofen had no effect on GABAA-mediated inhibiton induced by focal application of GABA to the granule cells. These results suggest that baclofen suppressed recurrent inhibition through an action mediated by GABAB receptors on inhibitory interneurons. They also suggest the net effect of baclofen was proepileptic because its disinhibitory effect was substantially greater than its suppressive effect on synaptic excitation.

Animals↗
PubMed1988

Abnormal hyperexcitability of hippocampal slices from kindled rats is transient.

The anatomic substrates and mechanisms responsible for the development and permanence of kindling remain to be determined. One region believed to play an important role in kindling development is the hippocampus. Epileptiform activity (K+-induced spontaneous bursting) was recently shown to be enhanced in hippocampal slices from kindled rats studied 1 day after kindling from the lateral entorhinal cortex (LEC). Identical results one month after kindling raised the possibility that hippocampal excitability might be permanently increased in kindled animals. One goal of the present study was to confirm this finding, and also to extend it in terms of both the anatomic extent and the duration of this excitability increase. Stimulus train-induced bursting (STIB) is an in vitro model of hippocampal epileptogenesis. Parallels between STIB and kindling suggested STIB might prove useful for studying mechanisms underlying kindling. To strengthen the relation of STIB to kindling, we examined whether slices from kindled animals would behave as if they had undergone STIB during kindling. K+-induced bursting and STIB were studied in hippocampal slices from control and kindled rats one day and about 3 months after completion of kindling from the right LEC. Both K+-induced bursting and STIB development were enhanced one day after kindling. The enhancement of K+-induced bursting was present in both temporal and septal slices from both the ipsilateral and the contralateral hippocampus. Neither of these proepileptic changes was detected 3 months after kindling.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1988

Partial C4A deficiency is associated with susceptibility to systemic lupus erythematosus in black Americans.

In a study of 59 black American patients with systemic lupus erythematosus (SLE), we found that partial C4A deficiency occurred twice as frequently as in 59 control subjects (32.3% versus 15.3%; P = 0.02). Complete C4A deficiency, however, occurred in only 1 patient and in no controls. Partial C4A deficiency is a risk factor for SLE in black, as well as in white, SLE populations studied to date. In contrast with white patients, complete C4A deficiency occurs relatively infrequently in black patients with SLE.

Adult↗
PubMed1988

Potential interactions between GABAb and cholinergic systems: baclofen augments scopolamine-induced performance deficits in the eight-arm radial maze.

Sixteen male Fischer-344N rats were trained on a eight-arm radial maze task for food reinforcement. The effects of various doses of baclofen (1.25 or 2.50 mg/kg) and scopolamine (0.188, 0.375, and 0.750 mg/kg) were determined alone and in combination. Relative to vehicle controls, baclofen alone did not affect performance in the radial arm maze (number correct in the first eight responses, total errors) or the time required to complete the maze. Scopolamine alone decreased the number of correct responses in the first eight arm choices, while increasing both the number of errors and the time necessary to complete the maze. When the two drugs were co-administered, baclofen had no effect on the number of errors or time required to complete the maze in the presence of scopolamine; however, in combination with the high dose of scopolamine, it significantly increased the number of errors made during the first eight choices. Baclofen thus can exacerbate some radial arm maze dificits produced by an anticholinergic drug. In a subsequent experiment to test the interaction between scopolamine and baclofen using a nonlearned behavior, baclofen (1.25 and 2.5 mg/kg) did not affect motor activity, whereas all doses of scopolamine (0.188-0.75 mg/kg) increased activity. The higher dose of baclofen attenuated scopolamine-induced hypermotility by 50%, but the lower dose of baclofen was not effective. These data demonstrate pharmacological interactions between baclofen, a drug used clinically for spaticity, and a drug having anticholinergic properties.

Animals↗
PubMed1988

Cardiolipin antibodies and null alleles of C4 in black Americans with systemic lupus erythematosus.

Twelve of 44 black American patients with systemic lupus erythematosus (SLE) (27%) studied during periods of disease activity had increased levels of IgG antibodies against cardiolipin (IgG aCL). IgG aCL occurred almost exclusively in patients who had a partial genetic deficiency of C4A or C4B. Eleven of 29 patients (38%) with a C4A or C4B deficiency allele had IgG aCL, compared with 1/15 patients (7%) who did not have C4A or C4B deficiency allele (p = 0.04). During periods when SLE was less active clinically, IgG aCL levels returned to normal in 10/12 patients. Active SLE, rather than null alleles, appeared to be associated with low C4 levels in patients with IgG aCL.

Adult↗
PubMed1988

Complete C4B deficiency in black Americans with systemic lupus erythematosus.

We report 3 black American patients with systemic lupus erythematosus (SLE) in whom C4B was completely deficient in plasma. They all exhibited antibody against the nucleoprotein antigen SSA (Ro), as well as cutaneous involvement, features that have been previously associated with complement deficiency states. IgG antibody against cardiolipin was also present in 2 patients, in association with a biologic false positive test for syphilis in one patient, and with thrombocytopenia in another. This is the first description of the clinical presentation of complete C4B deficiency in blacks with SLE.

Adult↗
PubMed1987

Seizure-like events in brain slices: suppression by interictal activity.

A major concern in epilepsy research is the relationship between ictal (seizure) electrophysiological activity and interictal (between seizure) activity. Much research is carried out in vitro using brain slice models. Although they allow detailed electrophysiology, the events recorded are generally more similar to interictal than ictal activity. We have described an in vitro model of epileptiform activity in the hippocampal slice (exposure to artificial cerebrospinal fluid containing no added magnesium) in which the events closely resemble those seen in vivo during seizures. However, this model is limited by the brief period during which this ictaform activity occurs before it is replaced by interictal-like activity. We now report that as the frequency of the interictal activity is suppressed by the GABAB agonist baclofen, the ictal activity returns. Moreover, when frequent interictal activity is reinduced, the ictal activity again is suppressed. These results suggest that interictal activity may decrease the probability of a seizure. Furthermore, they suggest that substances which may be shown to inhibit interictal activity in various models of epilepsy may not necessarily inhibit ictal activity.

Action Potentials↗
PubMed1987

Baclofen disrupts passive avoidance retention in rats.

Baclofen (Lioresal, Ciba-Geigy) is an analog of the inhibitory neurotransmitter GABA and is used clinically to control spasticity. Recent studies have demonstrated that this compound produces a marked inhibition of synaptically evoked responses in area CA3 of the hippocampal slice, suggesting that this drug could influence behavior mediated by the limbic system. In the present study, male rats of the Fischer-344 strain were trained on a one-trial passive avoidance task and tested for retention 1 week later. After the training trial, separate groups of rats received either 5 or 10 mg/kg/4 ml IP of baclofen or the distilled H2O vehicle immediately, 10 min, or 60 min after training. One week later, the rats that received baclofen immediately after training reentered the test chamber with a significantly higher frequency than controls, although no differences in vacillatory responses were observed between groups. Similar effects were observed following posttrial administration of chlordiazepoxide. In a separate experiment rats were tested for locomotor activity after receiving the same doses of baclofen. Although baclofen decreased activity during a 30-min period after dosing, rats exposed to baclofen showed no significant change in activity relative to controls 1 week later. These data are consistent with the interpretation that baclofen may interfere with memory consolidation or retention.

Animals↗
PubMed1987

The NMDA receptor antagonist 2-amino-5-phosphonovalerate blocks stimulus train-induced epileptogenesis but not epileptiform bursting in the rat hippocampal slice.

The role of N-methyl-D-aspartate (NMDA) receptors in producing stimulus train-induced bursting (STIB) was examined in area CA3 of the rat hippocampus. Extracellular recordings were made from the CA3 pyramidal cell layer. Bursting was induced by trains of electrical stimuli delivered to the stratum radiatum of CA3, or by bath application of NMDA. The specific NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV) was then bath applied to test its ability to block STIB and NMDA activated bursting. A dose-response relation for NMDA activation indicated that bath application of 1 and 5 microM NMDA had little or no effect on the response to a paired stimulus pulse (triggered response) and did not induce spontaneous bursting. Ten micromolar NMDA induced strong triggered and spontaneous bursting during the application of NMDA in 72% of the slices. Fifty to one hundred micromolar NMDA caused the abolition of the excitatory postsynaptic potential (EPSP) and orthodromic population spike and the decrease or abolition of the antidromic population spike. In the normal medium wash following 10 microM NMDA, those slices that produced triggered and spontaneous bursting in 10 microM NMDA underwent an early phase of decreased excitability in which spontaneous bursting occurred in only 6% of the slices that were bursting in NMDA. Later in the wash spontaneous bursting began occurring in half of the slices that were bursting in NMDA, and the excitability of the triggered bursts increased slightly. The ability of the NMDA receptor antagonist APV to block NMDA-activated bursting was tested. Bath application of 100 or 200 microM APV alone caused little change in the normal triggered response. When 10 microM NMDA was added to the APV solution, there was little or no change in the triggered response, and no spontaneous bursting occurred. However, when 100 or 500 APV was added to the NMDA solution after NMDA burst activation had occurred, triggered bursting was reduced, but not blocked, although spontaneous bursting was blocked. In those slices that continued bursting after the washout of NMDA, bath application of 100 or 500 microM APV reduced, but did not block, triggered bursting. Spontaneous bursting continued in all slices. The ability of APV to block the induction of bursting by trains of electrical stimuli was then tested.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1986

Magnesium-free medium activates seizure-like events in the rat hippocampal slice.

The effect of magnesium-free medium on the electrical activity in CA3 of the rat hippocampal slice was examined. Magnesium removal resulted in the development of spontaneous and triggered interictal-like bursting, followed by spontaneous ictal-like events and finally periodic clustered bursts. The ictal-like events consisted of a tonic firing phase and a phase of clustered burst discharges resembling the tonic and clonic phases of seizures. The return to normal medium resulted in spontaneous and triggered interictal-like bursts.

Action Potentials↗
PubMed1986

A novel, calcium-induced triphasic current response in silent, non-bursting Aplysia neurons.

The iontophoretic injection of Ca2+ ions into voltage-clamped, silent neurons of Aplysia californica results in a prolonged, triphasic current response. This response consists of: a tetraethylammonium-sensitive outward current during the injection; followed by an inward current 10-30 s after the end of the injection; and finally a long, slowly increasing outward current that lasts for several minutes before returning to baseline.

Animals↗
PubMed1986

Potassium-induced epileptiform activity in area CA3 varies markedly along the septotemporal axis of the rat hippocampus.

Hippocampal slices are generally treated as equivalent regardless of their site of origin along the septotemporal axis. In this study, spontaneous epileptiform bursting was induced in area CA3 of rat hippocampal slices by bathing them in 7 mM potassium. The frequency of spontaneous bursting was measured in all viable slices from 12 hippocampi. Burst frequency was found to vary markedly and in a consistent fashion with site of slice origin along the septotemporal axis. Burst frequency was maximal in slices from near the temporal end and declined progressively toward the septal end. This finding was independent of slicing angle. These results demonstrate that site of slice origin along the septotemporal axis is an important confounding variable in in vitro studies of hippocampal neuronal activity. Furthermore, they support the notion that the temporal portion of the hippocampus may be more prone to seizure activity than the septal hippocampus, possibly because of factors intrinsic to the hippocampus.

Action Potentials↗
PubMed1986

Attenuation of epileptiform bursting by baclofen: reduced potency in elevated potassium.

Baclofen is an analog of the inhibitory neurotransmitter, GABA, which is used clinically to control spasticity. Recent evidence has accumulated showing this compound to have profound inhibitory effects upon hippocampal neural activity at both the cellular and circuit levels, and to attenuate epileptiform bursting in the hippocampal slice. However, it does not appear as an anticonvulsant on most traditional drug screens. Baclofen can produce inhibition by increasing potassium conductance, and therefore may fail to appear efficacious in typical anticonvulsant screens due to techniques that cause rapid and massive increases in interstitial potassium. We tested the hypothesis that baclofen is less effective at attenuating epileptiform bursting in the hippocampal slice under conditions of elevated extracellular potassium. Male Sprague-Dawley rats were decapitated and hippocampal slices were prepared. Epileptiform bursting was induced by bathing the slices in an artificial cerebrospinal fluid solution which contained either 7.0 mM K+ or 30 microM bicuculline methiodide, or by stimulus train-induced bursting. In each of these media, baclofen was applied in a random presentation of concentration format. Baclofen attenuated epileptiform bursting in both bicuculline and elevated K+, although considerably higher concentrations were necessary to attenuate bursting in high K+ than in bicuculline or after stimulus train-induced bursting. These results further support the antiepileptic actions of baclofen and provide evidence that this drug may be of value for attenuating epileptiform activity when there is not a tonic elevation of interstitial brain potassium.

Action Potentials↗
PubMed1986

Membrane currents underlying bursting pacemaker activity and spike frequency adaptation in invertebrates.

Invertebrate systems have proved to be quite useful for the development of an understanding of some processes in the central nervous system (CNS). An understanding of the basic mechanisms of epilepsy will result from understanding not only how populations of neurons interact but also how the physiological processes in individual neurons are altered in epileptogenesis. Because invertebrate neurons have been so accessible to experimentation, it has been possible to explore in detail the basic mechanisms controlling neuronal excitability using these cells and to make some useful predictions about electrophysiological mechanisms that may be present in central neurons. This chapter deals with two electrophysiological processes that have been observed in invertebrate neurons and that may have some relevance to understanding the basic mechanisms of epilepsy. We review first the past and current studies of invertebrate burst firing neurons. It appears that the electrophysiological mechanisms producing burst firing may be present in CNS neurons participating in epileptogenesis. With caution, the information gleaned from invertebrate studies may be applicable to higher systems. The second process we consider is the phenomenon of spike frequency adaptation seen in invertebrates. Spike frequency adaptation is the process by which the firing rate of the neuron declines despite the maintenance of a constant stimulus. This process is not so thoroughly studied as burst firing, but it appears to represent a cellular mechanism designed to suppress prolonged periods of repetitive firing. Clearly, the suppression of such a process would produce excessive neuronal excitability, while its enhancement might have some anticonvulsant effects. The extreme sensitivity of spike frequency adaptation to barbiturates suggests such a possibility. These two electrophysiological processes are interesting in themselves and also because they may underlie the genesis or control of seizures. However, the greater significance is that, to understand the basic mechanisms of epilepsy, we may be well advised to examine neuronal processes in systems not considered to have seizure susceptibility.

Action Potentials↗
PubMed1986

Baclofen suppresses hippocampal epileptiform activity at low concentrations without suppressing synaptic transmission.

Baclofen is used clinically to treat spasticity, but has received little attention as a potential antiepileptic agent. To explore the antiepileptic potential of baclofen further, we tested its effect on stimulus train-induced bursting, an in vitro model of hippocampal epileptiform activity. In hippocampal slices prepared from male rats, extracellular field potentials were recorded in stratum pyramidale of CA3, and electrical stimuli were delivered to s. radiatum of CA3. After stable responses to single stimuli were established, stimulus trains were delivered every 5 min until stable triggered and spontaneous population bursting were elicited. (+/-)-Baclofen was bath-applied to the slices at varying concentrations to study its ability to suppress synaptic transmission and epileptiform activity. EC50 values for suppression of orthodromic population spike amplitude, of triggered burst duration and of spontaneous burst frequency were 2300, 355 and 26.9 nM, respectively; all statistically significantly different. These findings suggest that baclofen suppresses epileptiform electrical activity in the hippocampus at concentrations well below those which suppress normal synaptic transmission, and support renewed consideration of baclofen as an antiepileptic agent.

Animals↗