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M S Evans

Publications and source records attributed to M S Evans.

At least 37 records · Page 2Linked to original sources
PubMed1996

Midazolam inhibits long-term potentiation through modulation of GABAA receptors.

Benzodiazepine drugs (BZ) are used for anxiety, insomnia, and seizures. They worsen memory, especially in large doses, but the mechanism of this action is uncertain. In micromolar concentrations, benzodiazepines have been shown to reduce long-term potentiation (LTP), which could be a cellular basis for their amnesic action. We have found that the LTP-inhibiting effects of BZ occur in the nanomolar concentrations attained in humans, and that this effect occurs through modulation of GABAA receptor function. We recorded extracellular synaptic input/output (I/O) curves for population spikes (PS) and EPSPs in rat hippocampal slices before and after induction of LTP. LTP increased maximal PS and EPSPs and shifted I/O curves for PS and EPSPs to the left, reflecting increased synaptic responsiveness after LTP. Curves relating EPSPs to PS were also shifted, so that after LTP larger PS were elicited for the same size EPSP (E-S potentiation). Midazolam (0.5 microM) markedly inhibited the left-shift in PS I/O curves due to E-S potentiation but did not significantly affect other parameters. 8-Phenyltheophylline (10 microM), an adenosine receptor antagonist, did not prevent midazolam inhibition of LTP. Bicuculline, a GABAA receptor antagonist, caused a dose-dependent antagonism of midazolam's LTP inhibition. Our results suggest that benzodiazepines reduce LTP primarily through reduction of E-S potentiation, and that this effect occurs through modulation of GABAA receptor function. This could in part account for the ability of benzodiazepines to disturb new memory formation.

Animals↗
PubMed1996

Onset of neurologic deficits after treatment with dihydroergotamine in a patient with sagittal sinus thrombosis.

A woman with a 7-year history of intermittent migraine had 3 months of gradually worsening headaches. Initial neurologic examination including fundus examination was normal, and initial head computerized tomographic (CT) scan and magnetic resonance imaging (MRI) were thought to be normal. The patient was given dihydroergotamine (DHE-45), 1.0 mg, intravenously for relief of headache. Five hours later, she complained of severe diffuse headache and nausea. Neurologic examination showed left arm weakness and sensory loss, blurring of the left optic disc, and bilateral Babinski signs. Cerebral arteriography demonstrated thrombosis of the sagittal sinus, which in retrospect was present on the initial contrast CT scan and MRI scan. The patient's deficits worsened, and she eventually died 20 days later as a result of cerebral infarctions and increased intracranial pressure, despite attempts at selective thrombolysis of the sagittal sinus. DHE has potent venoconstrictive effects. We suspect that DHE helped precipitate neurologic deterioration in this patient with sagittal sinus thrombosis.

Adult↗
PubMed1996

Radiation-induced formation of a crosslink between base moieties of deoxyguanosine and thymidine in deoxygenated solutions of d(CpGpTpA).

A new type of tandem base lesion has been observed in d(CpGpTpA) X-irradiated in aqueous solution. The lesion is attributed to the formation of a covalent bond between the C8 carbon atom of guanine and the methyl carbon atom of thymine. This tandem base lesion is formed in the absence of oxygen. It is the main product produced by ionizing radiation under these conditions.

Acid Phosphatase↗
PubMed1995

Evidence for decreased calcium dependent potassium conductance in hippocampal CA3 neurons of genetically epilepsy-prone rats.

The genetically epilepsy-prone rat (GEPR) has become an important model to study genetic predisposition to epilepsy involving not only the brainstem but also forebrain structures. Previous work in CA1 hippocampal cells showed a reduction in spike frequency adaptation and only subtle changes in slow afterhyperpolarization (AHP). As important differences exist in calcium dependent potentials in the CA1 and CA3 hippocampal cells, we compared the membrane properties of hippocampal CA3 cells in GEPRs and Sprague-Dawley (SD) rats. There was no significant difference in the resting membrane potential, input resistance, charging time constant or rheobase between GEPRs and SD rat neurons. The action potential amplitude and the width at half maximal amplitude did not differ. A marked reduction in spike frequency adaptation accompanied by a very significant reduction in AHP was seen in the GEPR rats. Since calcium dependent potassium conductance produces both spike frequency adaptation and AHP, our results suggest that this conductance is reduced in the GEPR CA3 neurons.

Animals↗
PubMed1995

DNA damage in UVB-irradiated keratinocytes.

A DNA lesion which results from the breakdown of a pyrimidine base leaving a formamido remnant has been associated with oxidative stress. This lesion is shown to be produced in keratinocytes irradiated in culture with UVB light. The amount of formamido lesion produced is comparable to the amount of the 8-hydroxyguanine lesion. The two lesions were measured by 32P-postlabeling and electrochemical detection methods respectively.

Animals↗
PubMed1994

Inferior colliculus neuronal membrane and synaptic properties in genetically epilepsy-prone rats.

Previous studies using single-unit recording techniques have shown that the inferior colliculus is critical for audiogenic seizure initiation in genetically epilepsy-prone rats (GEPR). In order to investigate cellular abnormalities that may be important in causing audiogenic seizure susceptibility, intracellular recordings were made from neurons of inferior colliculus dorsal cortex (ICd) in a GEPR variety that exhibits severe audiogenic seizures (GEPR-9). GEPR neuronal membrane and synaptic properties were compared to those of normal Sprague-Dawley rats (SD), the strain from which GEPR were derived. We found six electrophysiological differences between GEPR and normal SD ICd neurons, all of which could promote seizures in GEPR. (1) Input resistance was higher in GEPR than in normal ICd neurons. (2) Threshold for repetitive action potential firing was closer to resting membrane potential in GEPR ICd neurons. (3) GEPR neurons showed faster repetitive spike firing than normal SD neurons. (4) Anode break spikes occurred at the offset of a hyperpolarizing pulse more often in GEPR than in normal SD neurons. (5) Stimulation of the commissure of the inferior colliculus caused synaptic paired pulse inhibition in normal ICd neurons, but paired pulse facilitation was always observed in GEPR neurons. (6) In GEPR, a large epileptiform depolarizing event could be elicited by strong electrical stimulation of the commissure of the inferior colliculus. In normal SD rats, similar epileptiform activity was seen only after application of bicuculline or NMDA. Our results suggest that both abnormal neuronal membrane properties and altered synaptic transmission are likely to contribute to seizure predisposition and audiogenic seizure initiation in GEPR.

Acoustic Stimulation↗
PubMed1994

Loss of synaptic inhibition during repetitive stimulation in genetically epilepsy-prone rats (GEPR).

Genetically epilepsy-prone rats (GEPR) are an animal model of generalized motor seizures. The underlying causes of the predisposition to seizures in GEPR have not been fully determined. The brainstem auditory system is critical for audiogenic seizures in GEPR, and neurophysiological abnormalities have been observed in these areas, but recent evidence suggests that non-auditory brain areas may also be abnormal. This may account for the lowered threshold in GEPR for various non-audiogenic seizures. Because the normal responses of the hippocampal Schaffer collateral/CA1 synapse are relatively well understood, we studied single and repetitive synaptic responses in hippocampal slices of GEPR in vitro. Our hypothesis was that altered excitatory or inhibitory synaptic transmission may contribute to GEPR non-audiogenic seizure predisposition. We recorded extracellular EPSPs, population spikes, and afferent volleys in hippocampal area CA1, and compared GEPR responses to those of Sprague-Dawley (SD) rats, the strain from which GEPR were derived. GEPR responses to single synaptic stimuli were not significantly different from SD. The second of a pair of closely spaced EPSPs or population spikes was larger in both GEPR and SD (paired pulse facilitation), but the magnitude of population spike facilitation was significantly increased in GEPR. Short trains of four stimuli caused inhibition of population spike firing in SD, an effect that was much reduced in GEPR. When SD slices were treated with bicuculline, a GABAA receptor antagonist, enhanced paired pulse facilitation and loss of inhibition during trains of stimuli were seen, similar to the patterns seen in GEPR.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1993

Dimethylsulfoxide (DMSO) blocks conduction in peripheral nerve C fibers: a possible mechanism of analgesia.

Dimethylsulfoxide (DMSO) is readily absorbed through skin, and relieves musculoskeletal pain when applied topically to painful areas. We studied the effects of DMSO on C-type nerve fibers, which mediate pain sensation. DMSO was applied directly to exposed cat sural nerves. C fiber conduction velocity was slowed by DMSO, even in low concentrations (5-7% v/v). Higher concentrations completely blocked C fiber conduction, with a minimum blocking concentration of 9%. Onset of nerve block was almost immediate with 15% DMSO or higher concentrations. C fiber blockade may account for analgesia with DMSO.

Action Potentials↗
PubMed1993

The differential lysis of phosphoester bonds by nuclease P1.

The hydrolysis by nuclease P1 of the 16 common deoxydinucleoside monophosphates was examined. The rates of hydrolysis of phosphodiester bond differ by more than two orders of magnitude; dinucleotide monophosphates of the type d(TpN) being most resistant and d(GpN) being next most resistant. The profiles of a mixture of the 16 common dinucleoside monophosphates and of DNA after partial hydrolysis by nuclease P1 and simultaneous treatment with acid phosphatase were compared. The resultant profiles are very similar, except for the appearance of 5-methyldeoxycytidine in the latter. Similar profiles are also obtained from a mixture of dinucleoside monophosphates and from DNA exposed to ionizing radiation beforehand. The 8-hydroxyguanine lesion and a formamido remnant of thymine appear in both profiles as a modified nucleoside and as modified dinucleoside monophosphate respectively. These results suggest that certain radiation induced DNA lesions can be selectively postlabelled based on their resistance to hydrolysis by nuclease P1. The nature of the nuclease P1-substrate interaction is discussed.

Animals↗
PubMed1993

32P-postlabeling assay for free radical-induced DNA damage: the formamido remnant of thymine.

A prominent lesion in DNA exposed to oxidative free radicals results from the degradation of thymine leaving a formamido remnant. A 32P-postlabeling assay has been developed for the detection of the formamido lesion. The assay is based on the circumstance that the lesion prevents hydrolysis by nuclease P1 of the phosphoester bond 3' to the damaged nucleoside. Thus, a nuclease P1 plus acid phosphatase digest of DNA generates mostly nucleosides whereas the formamido lesion is rendered as a modified dinucleoside monophosphate. Dinucleoside monophosphates, but not nucleosides, are apt substrates for 32P-postlabeling by polynucleotide kinase. The assay was applied to calf thymus DNA X-irradiated in oxygenated solution. The formamido lesion could be detected down to a dose of a few Gy.

Animals↗
PubMed1992

Characterization of two radiation-induced lesions from DNA: studies using nuclease P1.

Exposure of DNA oligomers to ionizing radiation in oxygenated solution reveals that the two lesions formed in highest yield are the 8-hydroxy modification of guanine and the formamido remnant of thymine. The effect of these lesions on the hydrolysis of the phosphodiester bond by nuclease P1 was studied. Whereas the 8-hydroxyguanine lesion does not affect hydrolysis of the adjacent 3' phosphoester bond by nuclease P1, the formamido lesion markedly retards hydrolysis. Consistent with the oligomer results, digestion of irradiated DNA polymer by nuclease P1 plus acid phosphatase yielded the 8-hydroxyguanine lesion, obtained as the modified nucleoside, and the formamido lesion, obtained as a modified dinucleotide.

DNA↗
PubMed1992

Analysis of DNA damage at the dinucleoside monophosphate level: application to the formamido lesion.

The dinucleoside monophosphates d(TpG), d(TpC), and d(TpT) were X-irradiated in oxygenated solution. In each case the modification of the dinucleoside in which the thymine base is degraded to a formamido remnant was observed as a principal product. The hydrolysis of the phosphoester bond of formamido-modified dinucleosides is much slower than that of the corresponding unmodified dinucleosides. This effect is also observable in the hydrolysis of irradiated DNA, where hydrolysis by nuclease P1 (plus acid phosphatase) generates the modified dinucleosides d(TFpN), TF being the modified thymidine. The total yield of the formamido lesion in all its forms, d(TFpN), exceeds the yield of any other base modification.

Chromatography, High Pressure Liquid↗
PubMed1991

The biomagnification of polychlorinated biphenyls, toxaphene, and DDT compounds in a Lake Michigan offshore food web.

The biomagnification of polychlorinated biphenyls (PCB), toxaphene, and the DDT family of metabolites was investigated in the epibenthic Mysis relicta (mysid), the benthic Pontoporeia hoyi (amphipod), plankton, particulate flux, surficial sediments, and Myoxocephalus thompsoni (deepwater sculpin) in southeastern Lake Michigan. DDE was the most strongly biomagnified compound, increasing 28.7 times in average concentration from plankton to fish. PCB increased 12.9 times in average concentration from plankton to fish while toxaphene increased by an average factor of 4.7. Particle flux was comprised of lower chlorinated PCB homologues (average chlorine number = 3.8) than the biota (4.5-5.0) and sediments (4.6), possibly reflecting strong influences from atmospheric deposition and/or zooplankton egestion. The percent of higher chlorinated PCB homologues (5 and 6 chlorine atoms per PCB molecule) increased from 54-56% of the total PCB in plankton and M. relicta, to 61% in P. hoyi, to 74% in sculpins. Amphipods contained greater concentrations than mysids of PCB, DDT residues, and toxaphene, possibly reflecting differences in habitat (benthic vs epibenthic) and diet (detritus vs plankton). Based on estimates of average areal biomass and contaminant concentration, offshore Lake Michigan P. hoyi populations contain approximately 15.0 times as much toxaphene, 9.5 times as much total DDT, and 12.0 times as much PCB as the offshore M. relicta populations. Thus, amphipods may represent a greater reservoir than mysids for contaminant storage and subsequent recycling in offshore Lake Michigan.

Animals↗
PubMed1990

Photographic grading in the retinopathy of prematurity cryotherapy trial.

We report a system for photographic grading of the posterior fundus features of retinopathy of prematurity and correlation of such features with potential future visual function. The severity of temporal vessel traction, retinal fold, macular ectopia, retinal detachment, retrolental mass, blood vessel attenuation, retinal pigment epithelial scarring, and cataract was assessed by review of photographs at the Fundus Photograph Reading Center, Portland, Ore, according to a scheme designed to avoid bias or knowledge of treatment status. Reliability for all features was in the fair to excellent range (kappa greater than .40), except for blood vessel attenuation (kappa = .18), which was not a factor in the final outcome determination. The grading scheme provided the basis for the 3-month conclusions of the multicenter trial of cryotherapy for retinopathy of prematurity. This system will have further application in the 12-month Cryotherapy for Retinopathy of Prematurity Study conclusions and in future long-term correlation with visual acuity as the trial patients mature.

Cataract↗
PubMed1990

Lithium enhances neuronal muscarinic excitation by presynaptic facilitation.

The mechanisms underlying the psychotropic actions of lithium are not established, but modulation of endogenous brain neurotransmitter systems is likely to be important. Several interactions of lithium with muscarinic responses have been reported, including a marked potentiation of seizures produced by muscarinic agonists. Because the mechanism by which lithium augments muscarinic seizures may be related to the mechanism by which it produces its psychotropic effects, we have studied the interaction of lithium and muscarinic agonists in vitro. Using rat hippocampal slices, we found that a muscarinic agonist, pilocarpine, increased postsynaptic neuronal excitability, but simultaneously decreased synaptic transmission because of presynaptic inhibition. Lithium did not alter pilocarpine's postsynaptic excitatory actions, but reversed its presynaptic inhibitory action, leading to markedly increased action potential firing. These presynaptic effects are not caused by alterations in presynaptic action potential shape or reliability of conduction, and do not involve pertussis toxin-sensitive G proteins. Activation of protein kinase C with phorbol-12,13-dibutyrate, or inhibition with H-7 and sphingosine, did not affect muscarinic presynaptic inhibition, but abolished lithium's ability to enhance synaptic transmission, suggesting that this effect of lithium involves protein kinase C. We propose that presynaptic facilitation accounts for lithium's potentiation of muscarinic seizures. Since these effects occur with concentrations of lithium used clinically, similar presynaptic effects in endogenous brain neurotransmitter systems may be important for lithium's psychotropic actions.

Animals↗
PubMed1989

Effects of chlorinated benzenes on diatom fatty acid composition and quantitative morphology. IV. Pentachlorobenzene and comparison with trichlorobenzene isomers.

Cells of the diatom Cyclotella meneghiniana were exposed in a closed system to 0.095 ppm pentachlorobenzene over a period of 5 days. Changes in fatty acid and morphological percent composition were monitored to determine the effect of the toxicant. The greatest morphological change observed was an increase in lipid volume. Most morphological changes occurred in the 1 hour and 5 day sampling periods. Few changes in morphological characteristics or fatty acid percent composition were observed at eight hours, when the cells were in the dark. The C18:1 and C20:5 fatty acids were most variable with exposure to pentachlorobenzene. Results suggest that at sublethal doses, lipophilic toxicants exert effects that are biphasic. That is, immediately measurable effects are observed in the cells that include increases in storage products and changes in membranous organelles. Long-term effects are postulated to be the result of mobilization of lipophilic toxicants that have partitioned into lipid stores and are more available when lipids are metabolized. Although pentachlorobenzene has a higher octanol/water partition coefficient, it appears to exert fewer cellular changes than any trichlorobenzene isomer.

Chlorobenzenes↗
PubMed1983

Multivariate statistics and meaning in the study of psychopathology.

A recent article dealing with Schneiderian first-rank symptoms illustrates a frequent occurrence: the use of sophisticated statistical data analysis without clear concepts of either psychopathology or statistics. The purpose of this article is to present some guidelines for the interpretation of multivariate statistics and to increase sensitivity to the importance of integrating underlying clinical concepts with statistical data analysis.

Humans↗