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Biomedical subjects

B A Wilson

Publications and source records attributed to B A Wilson.

At least 73 records · Page 4Linked to original sources
PubMed1996

The relationship between respiratory exchange ratio, plasma lactate and muscle lactate concentrations in exercising horses using a valved gas collection system.

A valved gas collection system for horses was validated, then used to examine the relationship between the respiratory exchange ratio (RER), and plasma and muscle lactate in exercising horses. Four healthy Standardbred horses were trained to breathe through the apparatus while exercising on a treadmill. Comparisons of arterial blood gas tensions were made at 3 work levels for each horse, without (control), and with the gas collection system present. At the highest work level, the arterial oxygen tension (PaO2) was significantly lower (P < 0.05), and the arterial carbon dioxide tension (PaCO2) was significantly higher (P < 0.05), than control levels when the apparatus was present; however arterial oxygen content remained unchanged. The horses completed a standardized incremental treadmill test on 4 occasions to determine the repeatability of measurements of oxygen consumption (VO2), carbon dioxide production (VCO2), inspired minute ventilation (VI), respiratory exchange ratio (RER), ventilatory equivalent for oxygen (VI/VO2), tidal volume (VT), and ventilatory frequency (VF). All gas exchange and respiratory measurements showed good reproducibility with the mean coefficient of variation of the 4 horses ranging from 3.8 to 12%. We examined the relationship between 3 indices of energy metabolism in horses performing treadmill exercise: respiratory exchange ratio (RER), central venous plasma and muscle lactate concentrations. A relationship between RER and plasma lactate concentration was established. To compare muscle and plasma lactate concentrations, the horses completed a discontinuous exercise test without the gas collection apparatus present. Significant relationships (P < 0.05), between plasma lactate concentration and RER, and between plasma and muscle lactate concentration, were described for each horse. The valved gas collection system produced a measurable but tolerable degree of interference to respiration, and provided reproducible measurements of gas exchange and ventilatory measurements. It was concluded that measurements of both gas exchange and blood lactate may be used to indicate increased glycolytic activity within exercising skeletal muscle.

Animals↗
PubMed1995

Role of glutamic acid 988 of human poly-ADP-ribose polymerase in polymer formation. Evidence for active site similarities to the ADP-ribosylating toxins.

Sequence similarities between the enzymatic region of poly-ADP-ribose polymerase and the corresponding region of mono-ADP-ribosylating bacterial toxins suggest similarities in active site structure and catalytic mechanism. Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. Replacement of any of 3 other nearby Glu residues had little effect. The Glu988 mutations produced similar changes in activity in the carboxyl-terminal 40-kDa catalytic fragment fused to maltose-binding protein: E988Q and E988A reduced polymer elongation > 2000-fold, and E988D approximately 20-fold. Smaller changes were seen in chain initiation. The mutations had little effect on the Km of NAD, indicating a predominantly catalytic function for Glu988. The results support the concept of similar active sites of the polymerase and the ADP-ribosylating toxins. Glu988 may function in polymer elongation similarly to the toxins' active site glutamate, as a general base to activate the attacking nucleophile (in the case of the polymerase, the 2'-OH of the terminal adenosine group of a nascent poly-ADP-ribose chain).

ADP Ribose Transferases↗
PubMed1995

Oxygen cost of ventilation in the resting horse.

The purpose of this study was to develop a technique to measure the oxygen cost of ventilation and the values of ventilatory parameters in seven normal horses rebreathing carbon dioxide (CO2). All the horses responded to increased inspiratory levels of CO2 by increasing their tidal volume (VT) and frequency of breathing (Vf). The mean (SE) oxygen cost litre-1 of ventilation, measured at rates of ventilation greater than 200 litres min-1 was 1.7 (0.04) ml litre-1, similar to that of normal human subjects ventilating submaximally. It was concluded that the CO2 rebreathing test is a practical, non-invasive means of measuring the oxygen cost of breathing and the ventilatory response to CO2 in horses.

Animals↗
PubMed1995

Dense amnesia in a professional musician following herpes simplex virus encephalitis.

We describe the memory functioning of C, a professional musician who became amnesic following herpes simplex encephalitis in 1985. Although transient amnesia in a professional musician has previously been described, this is the first reported case of chronic amnesia in a highly talented professional musician. C is unusual in three respects. First, his amnesia is particularly severe. Second, his amnesia includes semantic as well as episodic memory deficits. Third, he believes he has just woken up and his preoccupation with this state of 'just wakening' has persisted for over 9 years. This appears to be the result of a delusion rather than the consequence of his amnesia.

Amnesia↗
PubMed1995

Performance of adults with Down's syndrome on the children's version of the Rivermead Behavioural Memory Test: a brief report.

We gave the Rivermead Behavioural Memory Test for Children (RBMT-C) to 37 community dwelling adults with Down's syndrome. Ages ranged from 19 to 44 years (mean 29 years, SD 6 years). We wanted to know (a) if the test could be administered to this group and (b) how people with Down's syndrome compared with children aged 5 to 10 years. All subjects were able to participate in the test and all were 'off the floor'. Story recall was the hardest subtest for people with Down's syndrome, while remembering to deliver a message was the easiest. We discuss the possible use of this test in studies comparing older people with Down's syndrome with Alzheimer patients.

Adult↗
PubMed1994

Active-site mutations of diphtheria toxin. Tryptophan 50 is a major determinant of NAD affinity.

The two active-site tryptophans of diphtheria toxin, Trp-50 and Trp-153, were individually or jointly replaced with phenylalanine or alanine by directed mutagenesis of a synthetic gene for the toxin's catalytic A fragment. Substitution of Trp-50 with alanine (W50A) decreased the ADP-ribosyltransferase activity by nearly 10(5)-fold and reduced NAD-glycohydrolase activity beyond the limits of our detection. Effects of the W153A mutation on these activities were less dramatic, < 40-fold decrease in ADP-ribosylation and < 10-fold decrease in NAD glycohydrolysis. The W50F and W153F substitutions caused only minimal reductions (< 2-fold) in enzyme activities and NAD affinity. Decreases in affinity for NAD in the initial, ground state complex, as measured by intrinsic protein fluorescence, correlated well with the reductions in enzyme activity. None of the mutations caused greater than a 10-fold decrease in NAD affinity for the ternary Michaelis complex in the ADP-ribosylation reaction; and none caused significant increase in susceptibility to proteolytic digestion by trypsin. The results indicate that Trp-50 is a major determinant of NAD affinity. Also, they identify this residue as a candidate for modification in the development of inactive forms of the toxin for use in vaccine development.

Binding Sites↗
PubMed1994

Active-site mutations of the diphtheria toxin catalytic domain: role of histidine-21 in nicotinamide adenine dinucleotide binding and ADP-ribosylation of elongation factor 2.

Diphtheria toxin (DT) has been studied as a model for understanding active-site structure and function in the ADP-ribosyltransferases. Earlier evidence suggested that histidine-21 of DT is important for the ADP-ribosylation of eukaryotic elongation factor 2 (EF-2). We have generated substitutions of this residue by cassette mutagenesis of a synthetic gene encoding the catalytic A fragment (DTA) of DT, and have characterized purified mutant forms of this domain. Changing histidine-21 to alanine, aspartic acid, leucine, glutamine, or arginine diminished ADP-ribosylation activity by 70-fold or greater. In contrast, asparagine proved to be a functionally conservative substitution, which reduced ADP-ribosylation activity by < 3-fold. The asparagine mutant was approximately 50-fold-attenuated in NAD glycohydrolase activity, however. Dissociation constants (Kd) for NAD binding, determined by quenching of the intrinsic protein fluorescence, were 15 microM for wild-type DTA, 160 microM for the asparagine mutant, and greater than 500 microM NAD for the alanine, leucine, glutamine, and arginine mutants. These and previous results support a model of the ADP-ribosylation of EF-2 in which histidine-21 serves primarily a hydrogen-bonding function. We propose that the pi-imidazole nitrogen of His-21 hydrogen-bonds to the nicotinamide carboxamide, orienting the N-glycosidic bond of NAD for attack by the incoming nucleophile in a direct displacement mechanism, and then stabilizing the transition-state intermediate of this reaction.

Adenosine Diphosphate Ribose↗
PubMed1994

Inhibition of membrane translocation of diphtheria toxin A-fragment by internal disulfide bridges.

Fragment A of diphtheria toxin is translocated to the cytosol when the toxin is presented to receptor-positive cells. The toxin binds to cell surface receptors through its B-fragment, and after endocytotic uptake, the low endosomal pH triggers translocation of the A-fragment across the membrane. Translocation can also be induced at the level of the plasma membrane by exposure to low pH medium. Based on the diphtheria toxin crystal structure, we made five double cysteine mutants of the A-fragment, each expected to form an intramolecular disulfide bond. Four of the double cysteine mutants efficiently formed an intramolecular disulfide bridge, and these same mutants showed a strong reduction in their translocating ability. The inhibition of translocation was observed both when the toxin was endocytosed and when translocation was induced by exposing surface-bound toxin to low pH. The data indicate that extensive unfolding of the A-fragment is required for translocation.

Adenosine Diphosphate Ribose↗
PubMed1994

Biochemical characterization of yeast RAS2 mutants reveals a new region of ras protein involved in the interaction with GTPase-activating proteins.

We report biochemical characterization of two recently identified mutants of yeast RAS2, RAS2-E99K and RAS2-E130K. These mutants exhibit dominant activating phenotypes in yeast. Characterization of their intrinsic GTPase and GDP dissociation as well as their ability to stimulate adenylate cyclase showed that these activities of RAS2-E99K mutant protein were similar to those of the wild type protein. RAS2-E130K protein, on the other hand, differed from the wild type protein with a fast GDP dissociation rate and 2-fold higher activation of adenylate cyclase. When the sensitivity to GTPase-activating protein (GAP) was examined, we found that the RAS2-E99K protein was approximately 1200-fold less sensitive to NF1-GAP activity. In addition, the affinity for NF1 as revealed by competition binding experiments was reduced more than 150-fold with RAS2-E99K protein. Thus, the RAS2-E99K mutation affects interaction with GAP proteins. This mutation is particularly interesting because it is the first mutation identified in the alpha 3 region of ras protein that affects GAP interaction. The alpha 3 region appears to be directly involved in interaction with NF1, since peptides containing the sequence encompassing residue 99 of RAS2 inhibit NF1-GAP activity. These results suggest that the interaction between ras and GAP involves a larger region within ras than previously recognized.

Adenylyl Cyclases↗
PubMed1994

When implicit learning fails: amnesia and the problem of error elimination.

We propose that one of the major functions of explicit memory is the elimination of learning errors. The hypothesis is explored by means of a stem completion task in which subjects are presented with stems having many potential completions, and in the initial phase are either encouraged to guess, the "errorful" procedure, or are provided with the correct completion, the "errorless" condition. Learning is then tested over a sequence of nine trials. The performance of amnesic subjects who are assumed to have good implicit but bad explicit learning is compared with that of normal elderly subjects, who are assumed to have an intermediate level of explicit learning skill, and young controls who are expected to be high in both implicit and explicit learning capacity. As predicted, errorless learning is beneficial, with the effect being particularly marked for the amnesic group. A detailed analysis of the intrusion errors supports an interpretation of the results in terms of the relative contribution to the three groups of implicit learning, which is assumed to be particularly vulnerable to interference. Implications for the analysis of normal learning, and for the rehabilitation of brain damaged patients are discussed.

Adult↗
PubMed1994

Right neglect following right hemisphere damage?

From a sample of 90 stroke cases showing visual inattention following right hemisphere brain damage, 17 cases were identified who showed more inattention on the right than the left side on some tests. Eight of these subjects had CT scan-confirmed unilateral right hemisphere damage and one of these eight had MRI scan-confirmed unilateral right brain damage. A number of hypotheses are examined to explain this "paradoxical" right inattention. The most parsimonious proposes that right inattention is produced by an interaction of a compensatory left sided scanning strategy in association with a non-lateralised attentional loss.

Adult↗
PubMed1994

Syndromes of acquired dyslexia and patterns of recovery: a 6- to 10-year follow-up study of seven brain-injured people.

Seven subjects who were neurologically impaired following encephalitis (n = 2), head injury (n = 3), and stroke (n = 2) were referred several years previously because of acquired dyslexia. Two were almost totally alexic, 2 were surface dyslexic, 2 were deep dyslexic and 1 was a letter-by-letter reader. Following a period of rehabilitation, the 2 with alexia became surface dyslexic and letter-by-letter readers; 1 of the deep dyslexics showed some improvements but remained a deep dyslexic; and the letter-by-letter reader learned to read more quickly. At follow-up, 6 to 10 years later, there had been little significant change. The 2 subjects whose alexia resolved into surface dyslexia with letter-by-letter reading had increased their reading ages but remained surface dyslexic and letter-by-letter readers. The subject who had been a letter-by-letter reader was faster at easier and more frequently used words but slower at harder, less frequently used words. Changes in the other 4 subjects were negligible. Implications for rehabilitation are discussed.

Adolescent↗
PubMed1994

The Extended Rivermead Behavioural Memory Test: a measure of everyday memory performance in normal adults.

The Rivermead Behavioural Memory Test provides a well-validated instrument for detecting everyday memory problems in patient groups. It was however designed as a screening test, and thus is insufficiently sensitive to detect mild deficits, whether due to brain damage or to the introduction of a drug or stressor. The Extended Rivermead Behavioural Memory Test (ERBMT) increases the level of difficulty by doubling the amount of material to be remembered, by combining material from Forms A and B, and Forms C and D of the original test to produce two parallel versions of the new extended test. The sensitivity of the ERBMT was assessed by comparing the performance of a middle-aged and an elderly group of normal subjects, who would be expected to show modest differences in memory performance. The subtests varied in their sensitivity to this small age difference, but when performance was assessed in terms of scaled scores that allow an overall combined measure of memory performance to be calculated, the test proved sensitive (t = 4.87, P < 0.0001), and free of ceiling and floor effects. We suggest that the ERBMT provides a promising measure of everyday memory in normal adults.

Adult↗