Biomedical subjects

E Gordon

Publications and source records attributed to E Gordon.

At least 37 records · Page 2Linked to original sources

PubMed2001

Single-event-related potential analysis by means of fragmentary decomposition.

A recently developed fragmentary decomposition method is employed to analyse single-trial event-related potentials (ERPs), thereby extending the traditional method of averaging. Using a conventional auditory oddball paradigm with 40 target stimuli, single-trial ERPs in 40 normal subjects were analysed for midline scalp (Fz, Cz and Pz) recording sites. The normalization effect, reported in our previous study of eye blink EMGs and proposed to be a characteristic property of a wide class of non-stationary physiological processes, was found to apply to these single-trial ERPs. Fragmentary decomposition of single-trial ERPs may be regarded as re-statement of the normalization effect. This allows both pre-stimulus EEGs and post-stimulus ERPs to be regarded as overlapping generic mass potentials (GMPs), with a characteristic Gaussian amplitude spectrum. On theoretical and empirical grounds we uniquely deduce a model GMP using an introduced d" function, and physically support it by the resting and transient conditions. The model takes into account the shape of the component, which suggests a simple relationship between the peak latency and the time of the component onset. Given that GMPs may be manipulated and sorted out, we present principles of the fragmentary synthesis, i.e. probabilistic ERP reconstructions on the basis of individual and ensemble properties of its identified components. Summarizing the component quantification in the form of the dynamic model provides for the first time the opportunity to quantify all significant components in single-trial ERPs. This method of single-trial analysis opens up new possibilities of exploring the dynamical ERP changes within a recording trial, particularly in late component "cognitive" paradigms.

Adult↗

PubMed2001

Application of the comet and micronucleus assays to butterfish (Pholis gunnellus) erythrocytes from the Firth of Forth, Scotland.

This report describes an investigation of genotoxic effects in an inter-tidal fish species sampled along a pollution gradient in the Firth of Forth, Scotland, UK. The comet assay is an electrophoretic technique for measuring DNA breakage in nuclei from individual cells and has only recently been applied to field investigations of genotoxicity. The measurement of nuclear anomalies (NA), such as the presence of micronuclei (MN) and 'lobes', has been successfully utilised in many field studies of genotoxic effects of contaminated sediments. These two techniques were applied to nucleated red blood cells (RBC) from the butterfish, Pholis gunnellus. The comet assay was adapted and validated for use in this species. Fish were sampled from the inner Firth of Forth, which has a legacy of industrial contamination and the outer Firth of Forth which is comparatively clean. The analysis of DNA strand breakage using this technique did not reveal any significant differences between animals sampled from inner and outer zones of the Firth. In contrast, MN and NA frequencies were elevated in the inner polluted zone of the Firth compared to the outer zone. This study suggests: (1) there are genotoxic effects associated with contaminants in the inner Firth of Forth, and (2) the comet assay may not be a suitable genotoxicity biomarker in fish.

Animals↗

PubMed2001

Integrative psychophysiology.

This paper attempts to provide an overview of the current status and some possible future directions of 'Integrative Psychophysiology'. Exemplar integrations are offered for: (i) the theory of some of the more cited models of the brain as a system; (ii) a numerical simulation of brain dynamics (highlighting the plausibility of exploring mechanisms at the whole brain scale); and (iii) an empirical profile of disturbances in patients with schizophrenia (reflecting a prototypical disorder of overall brain instability and suboptimal integrative information processing). These 'integrative' dimensions provide a frame of reference for considering interrelationships among brain dynamics and behaviour, in health and disease.

Brain↗

PubMed2001

An integration of 40 Hz Gamma and phasic arousal: novelty and routinization processing in schizophrenia.

OBJECTIVES: Frontal and lateralized schizophrenia disturbances were examined in terms of arousal-modulated changes in 40 Hz Gamma activity. METHODS: Forty patients with schizophrenia and 40 age- and gender-matched controls were studied in a conventional auditory ERP oddball paradigm. We investigated sub-averaged Gamma activity based upon a simultaneous measure of electrodemal skin conductance response (phasic arousal) to differentiate novelty (large responses) from routinization (small or no responses). Both early Gamma (Gamma 1) and later induced Gamma (Gamma 2) activities were examined. RESULTS: Patients with schizophrenia (compared with controls) had significantly reduced Gamma 1 amplitude in the right hemisphere for novelty processing and delayed Gamma 2 latency in the left hemisphere for both novelty and routinization. Overall, reduced Gamma 1 amplitude in patients with schizophrenia was also evident. CONCLUSIONS: These findings indicate that the normal laterality of Gamma activity is specifically disturbed in schizophrenia in response to novel, but not routine (familiar) stimuli. The distinct pattern of findings suggests a dysregulation of activation across left and right hemispheres during initial attention and preparatory phases of information processing, in particular, in patients with schizophrenia.

Adult↗

PubMed2001

Alcohol and marijuana: effects on epilepsy and use by patients with epilepsy.

We review the safety of alcohol or marijuana use by patients with epilepsy. Alcohol intake in small amounts (one to two drinks per day) usually does not increase seizure frequency or significantly affect serum levels of antiepileptic drugs (AEDs). Adult patients with epilepsy should therefore be allowed to consume alcohol in limited amounts. However, exceptions may include patients with a history of alcohol or substance abuse, or those with a history of alcohol-related seizures. The most serious risk of seizures in connection with alcohol use is withdrawal. Alcohol withdrawal lowers the seizure threshold, an effect that may be related to alcohol dose, rapidity of withdrawal, and chronicity of exposure. Individuals who chronically abuse alcohol are at significantly increased risk of developing seizures, which can occur during withdrawal or intoxication. Alcohol abuse predisposes to medical and metabolic disorders that can lower the seizure threshold or cause symptoms that mimic seizures. Therefore, in evaluating a seizure in a patient who is inebriated or has abused alcohol, one must carefully investigate to determine the cause. Animal and human research on the effects of marijuana on seizure activity are inconclusive. There are currently insufficient data to determine whether occasional or chronic marijuana use influences seizure frequency. Some evidence suggests that marijuana and its active cannabinoids have antiepileptic effects, but these may be specific to partial or tonic-clonic seizures. In some animal models, marijuana or its constituents can lower the seizure threshold. Preliminary, uncontrolled clinical studies suggest that cannabidiol may have antiepileptic effects in humans. Marijuana use can transiently impair short-term memory, and like alcohol use, may increase noncompliance with AEDs. Marijuana use or withdrawal could potentially trigger seizures in susceptible patients.

Alcohol Drinking↗

PubMed2001

ERPs associated with and without an "orienting reflex" in patients with schizophrenia.

In this study, we measured traditional late components of the Event Related Potential (ERP: N 100, P 200, N 200 and P 300) in a conventional auditory oddball paradigm, but additionally and simultaneously assessed electrodermal "orienting reflexes (ORs)" in 40 patients with schizophrenia and 40 age and gender matched normal controls. The single epoch ERPs that did and did not evoke an OR, were sub-averaged separately. The control subjects (but not the patient group), revealed delayed P 300 latency in the ERP sub-averages without ORs (ERP-OR), compared with ERP sub-averages with ORs (ERP+OR). Between-group analysis showed reduced N 100, N 200 and P 300 amplitudes (as well as delayed P 300 latency) in the ERP+OR sub-average in patients with schizophrenia. In the ERP-OR sub-average, the patient group also had smaller N 100, N 200 and P 300 amplitudes, but larger P 200 amplitude (compared with normal controls). This study shows the potential to tease out physiologically based OR sub-processes, by simultaneous acquisition and analysis of ERPs and autonomic electrodermal activity. Such ERP sub-averages (based on autonomic responses) highlight that multiple processes overlap across the trial, and their delineation may elucidate more specific patterns of disturbance in schizophrenia, than traditional averaged measures.

Adult↗

PubMed2001

Event-related potentials to threat-related faces in schizophrenia.

Specialised network disturbances such as abnormalities in processing faces, may be associated with functional disturbances of interpersonal communication in schizophrenia. This study focused on the temporal dimension, investigating facial processing deficits in patients with schizophrenia (and non-patient controls) in a passive event-related potential (ERP) paradigm. ERPs invoked to an angry and neutral face stimulus were recorded in 27 patients with schizophrenia and 27 age and sex matched normal controls. Patients with schizophrenia showed a significant generalised delay, and diminished P200 amplitude (primarily frontal) for both stimuli-with more widespread regions of disturbance associated with the angry face. Normal controls, on the other hand, showed relatively reduced posterior P200 amplitude for angry compared to neutral faces, and a lateralised pattern of engagement in response to both stimuli. These findings indicate suboptimal processing of neutral faces in patients with schizophrenia, further exacerbated for affect laden angry faces.

Adult↗

PubMed2001

Sex differences, gamma activity and schizophrenia.

This study explores the possibility that the more favourable clinical prognosis in females with schizophrenia may be associated with their greater network interconnectedness, which is possibly reflected in enhanced "Gamma" (40 Hz) electrical brain activity. An auditory "oddball" task was administered to 35 patients with schizophrenia and 35 age and sex matched controls (25 males and 10 females). Peak Gamma amplitude (from a time series of Gamma activity averaged for 40 target stimuli, as well as the immediately preceding 40 background tones) was examined across 19 sites. Peak Gamma activity occurred 250 to 450 ms in targets and 350 to 550 ms in backgrounds. Multiple within and between group MANOVAs were undertaken analysing both Peak Gamma amplitude (microvolts) and latency (milliseconds). Within-group, the control males showed a pattern of earlier Gamma latency in the right compared with the left hemisphere (F(1, 33)=3.70, p<.06), while control females exhibited delayed latency frontally compared with the posterior region (F(1, 33)=6.25, p<.04). This male lateralization finding and the anterior/posterior gradient in females is consistent with Goldberg's model. The patient group however, failed to show this male lateralized and female frontal-posterior pattern of Gamma activity, suggesting suboptimal network integration in the patient group, in both males and females.

Acoustic Stimulation↗

PubMed2001

The modulation of late component event related potentials by pre-stimulus EEG theta activity in ADHD.

Electroencephalography (EEG) and Event Related Potentials (ERPs) studies in ADHD have generally been studied separately. This study examined these measures simultaneously in 54 adolescent unmedicated ADHD males and age and gender matched normal controls during an auditory oddball paradigm. Compared with controls, ADHD patients showed increased pre-stimulus EEG Theta activity and post-stimulus reduced N200 amplitude, increased P200 amplitude and delayed N200 and P300 latencies evoked to target stimuli. Moreover, Theta activity was negatively correlated with N200 amplitude and positively correlated with P200, N200 and P300 latency in ADHD. There were no correlations in the control group. Pre-stimulus preparatory state increases in Theta activity in ADHD may underlie some of the reported disturbances in information processing reflected in ADHD.

Adolescent↗

PubMed2001

The topography of quantified electroencephalography in three syndromes of schizophrenia.

This study investigated the association between quantified electroencephalography (qEEG) and three psychopathological syndromes, derived by a factor analysis of the symptom profile of a group of 40 subjects diagnosed with schizophrenia. An initial comparison with aged and sex matched normal controls showed an overall increase in slow wave activity in subjects with schizophrenia. The symptomatology of the subjects with schizophrenia was then factor analysed into three psychopathological syndromes that closely resembled Liddle's (1987b) original delineation. Correlations were undertaken between the three syndrome scores and qEEG. The "psychomotor poverty" factor was associated with increased beta activity most marked posteriorly and increased delta activity (accounted for by the effects of medication). The "disorganisation" factor was associated with widespread negative correlations in the alpha and beta bands and the "reality distortion" factor was associated positively with left anterior alpha activity. These distinct patterns of qEEG that clearly differentiate between the three syndromes, may contribute towards elucidating the underlying pathophysiological processes in schizophrenia. The results support the use of symptom based syndromes in reducing the diversity of findings in schizophrenia.

Adolescent↗

PubMed2000

Crystal structure of UDP-N-acetylmuramoyl-L-alanyl-D-glutamate: meso-diaminopimelate ligase from Escherichia coli.

UDP-N-acetylmuramoyl-l-alanyl-d-glutamate:meso-diaminopimelate ligase is a cytoplasmic enzyme that catalyzes the addition of meso-diaminopimelic acid to nucleotide precursor UDP-N-acetylmuramoyl-l-alanyl-d-glutamate in the biosynthesis of bacterial cell-wall peptidoglycan. The crystal structure of the Escherichia coli enzyme in the presence of the final product of the enzymatic reaction, UDP-MurNAc-l-Ala-gamma-d-Glu-meso-A(2)pm, has been solved to 2.0 A resolution. Phase information was obtained by multiwavelength anomalous dispersion using the K shell edge of selenium. The protein consists of three domains, two of which have a topology reminiscent of the equivalent domain found in the already established three-dimensional structure of the UDP-N-acetylmuramoyl-l-alanine: D-glutamate-ligase (MurD) ligase, which catalyzes the immediate previous step of incorporation of d-glutamic acid in the biosynthesis of the peptidoglycan precursor. The refined model reveals the binding site for UDP-MurNAc-l-Ala-gamma-d-Glu-meso-A(2)pm, and comparison with the six known MurD structures allowed the identification of residues involved in the enzymatic mechanism. Interestingly, during refinement, an excess of electron density was observed, leading to the conclusion that, as in MurD, a carbamylated lysine residue is present in the active site. In addition, the structural determinant responsible for the selection of the amino acid to be added to the nucleotide precursor was identified.

Amino Acid Sequence↗

PubMed2000

The effects of beta(1)-blockade on oxidative metabolism and the metabolic cost of ventricular work in patients with left ventricular dysfunction: A double-blind, placebo-controlled, positron-emission tomography study.

BACKGROUND: The mechanism for the beneficial effect of beta-blocker therapy in patients with left ventricular (LV) dysfunction is unclear, but it may relate to an energy-sparing effect that results in improved cardiac efficiency. C-11 acetate kinetics, measured using positron-emission tomography (PET), are a proven noninvasive marker of oxidative metabolism and myocardial oxygen consumption (MVO(2)). This approach can be used to measure the work-metabolic index, which is a noninvasive estimate of cardiac efficiency. METHODS AND RESULTS: The aim of this study was to determine the effect of metoprolol on oxidative metabolism and the work-metabolic index in patients with LV dysfunction. Forty patients (29 with ischemic and 11 with nonischemic heart disease; LV ejection fraction <40%) were randomized to receive metoprolol or placebo in a treatment protocol of titration plus 3 months of stable therapy. Seven patients were not included in analysis because of withdrawal from the study, incomplete follow-up, or nonanalyzable PET data. The rate of oxidative metabolism (k) was measured using C-11-acetate PET, and stoke volume index (SVI) was measured using echocardiography. The work-metabolic index was calculated as follows: (systolic blood pressure x SVI x heart rate)/k. No significant change in oxidative metabolism occurred with placebo (k=0.061+/-0.022 to 0.054+/-0.012 per minute). Metoprolol reduced oxidative metabolism (k=0.062+/-0. 024 to 0.045+/-0.015 per minute; P:=0.002). The work-metabolic index did not change with placebo (from 5.29+/-2.46 x 10(6) to 5.14+/-2. 06 x 10(6) mm Hg. mL/m(2)), but it increased with metoprolol (from 5. 31+/-2.15 x 10(6) to 7.08+/-2.36 x 10(6) mm Hg. mL/m(2); P:<0.001). CONCLUSIONS: Selective beta-blocker therapy with metoprolol leads to a reduction in oxidative metabolism and an improvement in cardiac efficiency in patients with LV dysfunction. It is likely that this energy-sparing effect contributes to the clinical benefits observed with beta-blocker therapy in this patient population.

Acetates↗

PubMed2000

Heme ligation and conformational plasticity in the isolated c domain of cytochrome cd1 nitrite reductase.

The heme ligation in the isolated c domain of Paracoccus pantotrophus cytochrome cd(1) nitrite reductase has been characterized in both oxidation states in solution by NMR spectroscopy. In the reduced form, the heme ligands are His69-Met106, and the tertiary structure around the c heme is similar to that found in reduced crystals of intact cytochrome cd1 nitrite reductase. In the oxidized state, however, the structure of the isolated c domain is different from the structure seen in oxidized crystals of intact cytochrome cd1, where the c heme ligands are His69-His17. An equilibrium mixture of heme ligands is present in isolated oxidized c domain. Two-dimensional exchange NMR spectroscopy shows that the dominant species has His69-Met106 ligation, similar to reduced c domains. This form is in equilibrium with a high-spin form in which Met106 has left the heme iron. Melting studies show that the midpoint of unfolding of the isolated c domain is 320.9 +/- 1.2 K in the oxidized and 357.7 +/- 0.6 K in the reduced form. The thermally denatured forms are high-spin in both oxidation states. The results reveal how redox changes modulate conformational plasticity around the c heme and show the first key steps in the mechanism that lead to ligand switching in the holoenzyme. This process is not solely a function of the properties of the c domain. The role of the d1 heme in guiding His17 to the c heme in the oxidized holoenzyme is discussed.

Cytochromes↗

PubMed2000

The neural correlates of orienting: an integration of fMRI and skin conductance orienting.

In fMRI studies, the averaging of neural activity across multiple trials might obscure important psychophysiological subprocesses. The orienting response (OR) is a distinctive subprocess signalling the active orientation of attention towards potentially significant events. We sought to elucidate fMRI activity associated with visual stimuli that did or did not evoke simultaneously recorded electrodermal ORs (using customised skin conductance recording). 'With-OR' stimuli were associated with significant activity in the hippocampus, anterior cingulate and ventromedial prefrontal cortex. Averaged analysis revealed activity only in the expected visual circuits. Our results suggest that potentially significant stimuli (with-OR) activate different functional networks to familiar (without-OR) stimuli, and that orienting may therefore be an informative subprocess to consider in cognitive fMRI studies.

Attention↗

PubMed2000

The crystal structure of the penicillin-binding protein 2x from Streptococcus pneumoniae and its acyl-enzyme form: implication in drug resistance.

Penicillin-binding proteins (PBPs), the primary targets for beta-lactam antibiotics, are periplasmic membrane-attached proteins responsible for the construction and maintenance of the bacterial cell wall. Bacteria have developed several mechanisms of resistance, one of which is the mutation of the target enzymes to reduce their affinity for beta-lactam antibiotics. Here, we describe the structure of PBP2x from Streptococcus pneumoniae determined to 2.4 A. In addition, we also describe the PBP2x structure in complex with cefuroxime, a therapeutically relevant antibiotic, at 2.8 A. Surprisingly, two antibiotic molecules are observed: one as a covalent complex with the active-site serine residue, and a second one between the C-terminal and the transpeptidase domains. The structure of PBP2x reveals an active site similar to those of the class A beta-lactamases, albeit with an absence of unambiguous deacylation machinery. The structure highlights a few amino acid residues, namely Thr338, Thr550 and Gln552, which are directly related to the resistance phenomenon.

Acylation↗

PubMed2000

Synchronous cortical gamma-band activity in task-relevant cognition.

Widespread synchronous oscillatory activity, particularly in the gamma ('40 Hz') band, has been postulated to exist in the brain as a mechanism underlying binding. A new method of examining phase synchronicity across multiple electrode sites in specific EEG frequency bands as a function of time was employed, in a conventional cognitive ERP paradigm in 40 normal subjects. A significant late post-stimulus gamma synchronicity response occurred for task-relevant stimuli, whereas for task-irrelevant stimuli no such response was evident. However, an early response was seen for both task-relevant and irrelevant stimuli. This is the first empirical demonstration that widespread synchronous high frequency oscillations occur in humans in relation to cognition.

Acoustic Stimulation↗

PubMed2000

Gamma activity in schizophrenia: evidence of impaired network binding?

OBJECTIVES: Gamma ('40 Hz') rhythms may play a role in the integration of sensory processing activity. Impaired temporal integration may be a key feature of the associated disturbances in schizophrenia. This is the first study to examine the time course of Gamma activity induced in response to stimuli in this disorder. METHODS: Gamma activity induced in response to task-relevant and irrelevant auditory oddball stimuli was examined in 35 medicated schizophrenics and 35 age- and gender-matched normal controls. We employed a moving Welch window with short time FFT to examine the time course of Gamma amplitude. The amplitude spectrum for each time point was de-trended to eliminate any contribution of broad spectrum activity (EEG or EMG) to Gamma amplitude. RESULTS: For targets, schizophrenics showed a significant decrease in post-stimulus Gamma response amplitude in left hemisphere and frontal sites and an increase in right hemisphere and parieto-occipital sites (P<0.0009). The abnormalities correlated with PANSS general symptom scores. In the non-targets (at a different latency), schizophrenics showed a widespread Gamma decrease (P<0.0005). CONCLUSIONS: The Gamma findings in non-targets may reflect an abnormality in appropriately processing irrelevant stimuli. This could result in defective processing of the context (integration) of relevant target information.

Adult↗

PubMed2000

Misattribution of sensory input reflected in dysfunctional target:non-target ERPs in schizophrenia.

BACKGROUND: While numerous studies have found disturbances in the Event-Related Potentials (ERPs) of patients with schizophrenia linked to task relevant target stimuli (most notably a reduction in P300 amplitude), few have examined ERPs to task irrelevant non-targets. We hypothesize, from current models of dysfunction in information processing in schizophrenia, that there will be less difference between ERPs to targets and non-targets in patients with schizophrenia than in controls. METHODS: EEGs were recorded for 40 subjects with schizophrenia and 40 age and sex matched controls during an auditory oddball reaction time task. ERPs to the targets and non-targets immediately preceding the targets were averaged separately. RESULTS: There was a disturbance in ERPs to targets but also to non-targets (reduced N100 amplitude and earlier P200 latency) and the difference between target and non-target ERP components (N100 and P200 amplitude and P200 latency), was significantly reduced in the schizophrenic group compared with controls. CONCLUSIONS: These findings suggest a disturbance in processing task relevant and irrelevant stimuli, consistent with Gray's (1998) hypothesis of misattributions in the 'match:mismatch' of novel (target) and familiar (non-target) sensory input compared with stored information.

Adult↗