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Biomedical subjects

M J Taylor

Publications and source records attributed to M J Taylor.

At least 91 records · Page 5Linked to original sources
PubMed1999

Effect of methylphenidate on attention in children with attention deficit hyperactivity disorder (ADHD): ERP evidence.

Methylphenidate is the most common treatment for attention deficit hyperactivity disorder (ADHD) and has been shown to improve attention and behaviour. However, the precise nature of methylphenidate on specific aspects of attention at different dose levels remains unclear. We studied methylphenidate effects in ADHD from a neurophysiological perspective, recording event-related potentials (ERPs) during attention task performance in normal controls and children with ADHD under different dose conditions. Twenty children with ADHD and 20 age matched controls were assessed with a continuous performance task requiring subjects to identify repeating alphabetic characters. ERPs and behavioural measures were recorded and analyzed for trials where a correct response was made. The ADHD group was assessed off drug (baseline) and on placebo, low (0.28 mg/kg) and high (0.56 mg/kg) dose levels of methylphenidate. The results showed that the ADHD group at baseline was more impulsive and inattentive than controls and had shorter P2 and N2 latencies and longer P3 latencies. Low dose methylphenidate was associated with reduced impulsivity (fewer false alarms) and decreased P3 latencies, whereas the higher dose level was associated with reduced impulsivity and less inattention (more hits), as well as increased P2 and N2 latencies and decreased P3 latencies. Amplitudes were unaffected and there were no adverse effects of the higher dose for any of the children. These results suggest differential dosage effects and a dissociation between dose levels and aspects of processing.

Attention↗
PubMed1999

A comparison of flexible and constrained haptens in eliciting antibody catalysts for paraoxon hydrolysis.

A new amine-oxide hapten was employed as an antigen, producing seven monoclonal antibodies (mAbs) from a panel of 20 that catalyzed paraoxon hydrolysis. The current hapten design differs from that previously described in that the molecule is inherently more flexible than its constrained predecessor. One of the seven antibody catalysts, mAb 1H9, showed the highest activity and was selected for detailed study. At pH = 8.77, the catalytic hydrolysis of paraoxon by mAb 1H9 followed Michaelis Menten kinetics affording a k(cat) = 3.73 x 10(-4) min(-1) and a Km = 1.12 mM with a rate acceleration k(cat)/k(uncat) = 56. The hapten was found to be a competitive inhibitor of antibody-catalyzed paraoxon hydrolysis with a Ki = 0.54 mM. A comparison of both the number and proficiency of antibody catalysts obtained when utilizing a flexible versus constrained hapten indicates that, for paraoxon hydrolysis, constrained haptens elicit superior catalysts, suggesting that further development should begin with the use of constrained haptens in producing more proficient antibody catalysts for paraoxon hydrolysis.

Aminocaproates↗
PubMed1999

ERP evidence of developmental changes in processing of faces.

OBJECTIVES: There is disagreement in the behavioural literature, as to whether face processing undergoes qualitative or quantitative change with age. METHODS: We studied event-related potentials (ERPs) associated with facial processing in 48 children (4-14 years) and 12 adults. Five categories of stimuli were presented: faces, cars, scrambled faces, scrambled cars, butterflies. The butterflies were targets (P = 12%); the other stimulus categories were equally represented and all were non-targets. RESULTS: An N170 was recorded only to the faces at posterior temporal sites and in adults it was largest at T6'. This component was seen across age groups, but at steadily increasing latencies in younger children. Age-related increases in N170 amplitude were found at T6'. In children under 12 years of age, the frontal P170 was not reliably seen. CONCLUSION: This study suggests that the underlying neural basis associated with processing faces matures in a gradual, quantitative manner throughout childhood.

Adolescent↗
PubMed1999

Neurophysiological measures of reading difficulty in very-low-birthweight children.

Twenty-four 8-10-year-old children (13 very low birthweight, 11 control) performed a lexical decision and a semantic classification task while event-related potentials (ERPs) were recorded. Both groups were within normal range on standardized reading tests, but the very-low-birthweight group had lower scores. There were no differences between groups in reaction times or accuracy for ERP tasks. On analyses of P2a (246 ms anteriorly), P2p (336 ms posteriorly), N2a (356 ms anteriorly), and N2p (396 ms posteriorly) peaks and a late positive component, control children showed greater right than left asymmetry at P2p and greater left than right asymmetry at N2a. Very-low-birthweight children showed less asymmetry. For the late positive component, both groups showed greater left than right asymmetry, which was more marked for the semantic classification task. The results suggest that very-low-birthweight children display differing cortical utilization during reading.

Child↗
PubMed1999

Use of oral reading to estimate premorbid intellectual and neuropsychological functioning.

Judgment of neuropsychological decline is typically made by comparing a patient's current cognitive performance to data from demographically similar normal individuals. Even within narrowly defined demographic categories, however, there is variability in level of performance, approximating the normal curve. The present study explored the degree to which oral reading scores on the American National Adult Reading Test (ANART) could more accurately predict a person's test performance relative to other demographically similar individuals. In a sample of 141 neurologically healthy participants, the ANART added modestly to the precision of WAIS-R Verbal and Full Scale IQ and Learning score predictions, beyond that achieved by demographics alone; however, ANART score did not significantly improve estimation of Performance IQ, Average Impairment Rating, or Memory score. Use of the ANART tended to improve demographic predictions primarily with "outlier" participants whose oral reading skills were relatively poor. For Verbal IQ, ANART helped with participants who had both poor ANART and relatively high education. Oral reading can be useful for estimating premorbid verbal intelligence and learning in combination with demographic variables, but it does not appear to improve estimates of other neurocognitive abilities.

Adult↗
PubMed1999

The impact of HIV-related neuropsychological dysfunction on driving behavior. The HNRC Group.

HIV infection often results in neuropsychological (NP) impairment. In order to assess the impact that HIV-related NP deficits may have on automobile driving, we evaluated 68 HIV-seropositive drivers using an NP battery and two PC-based driving simulations. Thirty-two participants were classified as NP impaired; most (72%) evidenced only mild impairment, and none met criteria for HIV-associated dementia. After controlling for degree of immunosuppression and disease stage, NP-impaired participants failed a previously validated driving simulation at a much higher rate than cognitively intact participants [OR = 5.3, 95% CI (1.7, 17.0), p = .006]. Similarly, on a simulation of city driving, NP impaired participants were more likely to fail based upon the number of accidents [OR = 6.1, 95% CI (1.5, 24.6), p = .01]. Simulator performance was predicted by functioning in a number of NP domains, with NP tests accounting for 13-30% of the variance on the simulations. Although it would be premature to extrapolate these findings to impairment in on-the-road driving, they do argue for greater attention to the impact that even mild HIV-related NP deficits may have on driving skills.

AIDS Dementia Complex↗
PubMed1999

Insulin delivery governed by covalently modified lectin-glycogen gels sensitive to glucose.

A glucose-sensitive gel formulation containing concanavalin A and glycogen has been reported previously. Precipitation resulting from the addition of concanavalin A to glycogen has been documented, but the formation of glucose-sensitive gels based on lectin-glycogen interactions is novel and used here in our studies. An improved in-vitro self-regulating drug-delivery system, using covalently modified glucose-sensitive gels based on concanavalin A and a polysaccharide displacement mechanism, is described. The successful use of the covalently modified gels addresses a problem identified previously where significant leaching of the mitogenic lectin from the gel membranes of non-coupled gels was encountered. Concanavalin A was covalently coupled to glycogen by use of derivatives of Schiff's bases. The resulting gels, like the non-coupled gels, were shown to undergo a gel-sol transformation in response to glucose. Insulin delivery was demonstrated using this covalently modified system in conditions of repeated glucose triggering at 20 degrees C and 37 degrees C. The magnitude of the response was less variable than for the dextran-based gels studied previously. The performance of this system has been improved in terms of concanavalin A leaching. This could, therefore, be used as the basis of the design of a self-regulating drug-delivery device for therapeutic agents used to treat diabetes mellitus.

Biological Transport↗
PubMed1999

Developmental changes in early cognitive processes.

The three paradigms presented in this paper demonstrate the value of ERPs in examining the development of early cognitive processes. Although we have presented only three examples, early cognitive processing could be investigated in a wide range of paradigms using ERPs, in normal as well as clinical populations. Clearly, a next step in understanding the age-related changes in these cognitive processes is to employ dipole source localization to examine the involvement of different generators and their maturation. The final conclusion is that developmental studies are important as they can contribute to our understanding of models of processing and of the generators of ERPs, in terms of cognition as well as neuroanatomy. Hence, the models of cognitive processes in adults should include the development of those processes through childhood.

Adult↗
PubMed1998

Tropomyosin implicated in host protective responses to microfilariae in onchocerciasis.

A cDNA from adult female Onchocerca volvulus encoding the C-terminal portion of a tropomyosin isoform (termed MOv-14) has been shown previously to confer protective immunity in rodent models of onchocerciasis. The full-length sequence (designated Ov-tmy-1) obtained by PCR amplification, codes for a protein of 33 kDa and shares 91% identity with tropomyosins from other nematodes, falling to 57% identity with human alpha-tropomyosin. Ov-TMY-1 migrates with an apparent molecular mass of 42 kDa on SDS/PAGE and is present in all life-cycle stages, as determined by immunoblotting. Immunogold electron microscopy identified antigenic sites within muscle blocks and the cuticle of microfilariae and infective larvae. Anti-MOv14 antibodies were abundant in mice exhibiting serum-transferable protection against microfilariae conferred by vaccination with a PBS-soluble parasite extract. In contrast, little or no MOv14-specific antibody was present in mice inoculated with live microfilariae, in which resistance is mediated by antibody-independent mechanisms. In human infections, there was an inverse correlation between anti-tropomyosin IgG levels and densities of microfilariae in the skin. Seropositivity varied with the relative endemicity of infection. An immunodominant B cell epitope within Ov-TMY-1 (AQLLAEEADRKYD) was mapped to the N terminus of the MOv14 protein by using sera from protectively vaccinated mice. Intriguingly, the sequence coincides with an IgE-binding epitope within shrimp tropomyosin, believed to be responsible for hypersensitivity in individuals exhibiting allergy to shellfish. IgG and IgE antibodies reacting with the O. volvulus epitope were detected in human infections. It is concluded that antibody responses to tropomyosin may be important in limiting microfilarial densities in a proportion of individuals with onchocerciasis and have the potential to mediate hypersensitivity reactions to dead microfilariae, raising the possibility of a link with the immunopathology of infection.

Adult↗
PubMed1998

IL-5-dependent immunity to microfilariae is independent of IL-4 in a mouse model of onchocerciasis.

Th2 lymphocyte responses under the control of IL-4 and IL-5 are frequently associated with protective responses to parasitic helminths. Studies on the role of these cytokines in acquired resistance to parasitic nematodes indicate that, in the case of gastrointestinal nematodes, immunity is mediated by IL-4, while immunity to tissue-dwelling nematodes is dependent on IL-5. Here we investigate the role of IL-5 and eosinophils in protective immunity to Onchocerca microfilariae in IL-4-deficient mice. In the absence of IL-4, and despite the up-regulation of Th1-type responses, immunity remains dependent on IL-5 and eosinophils. Protection was unaffected by the absence of Ab in B cell-deficient mice, confirming that IL-5 is not acting via either B cell differentiation, Ag presentation, or isotype switching mechanisms. These data demonstrate the dissociation of IL-4 and IL-5 in a functional model of protective immunity to a tissue dwelling nematode and cast doubt on the role of IL-4 in the generation of CD4+ T cell-mediated, IL-5-dependent immunity to Onchocerca microfilariae. Importantly, they also segregate T cell-mediated mechanisms of protective immunity from those characterized in ocular pathologic responses in onchocerciasis, which are dependent on IL-4.

Animals↗
PubMed1998

Cloning and sequencing of cDNA encoding bovine tumor necrosis factor (TNF)-receptor I.

Tumor necrosis factor (TNF) is a multipotent cytokine produced by activated macrophages and lymphocytes and its activity is mediated by specific cell surface receptors, TNF-RI and TNF-RII. We have isolated and analyzed a cDNA encoding bovine TNF-RI gene and compared it with known TNF-RI sequences from other species. The cDNA sequence for the coding region of bovine TNF-RI shows 80% homology with porcine TNF-RI and 77% with human TNF-RI. The cDNA sequence of bovine TNF-RI codes for 471 amino acids and shows 75% and 67% identity with the amino acid sequences of porcine TNF-RI and human TNF-RI, respectively. The predicted bovine TNF-RI amino acid sequence consists of a signal peptide, an extracellular domain, a transmembrane region and a cytoplasmic tail. The extracellular region contains four repeated cysteine rich domains, which are conserved in all species. Northern blot results show that bovine TNF-RI gene is expressed in neutrophils and mononuclear leukocytes.

Amino Acid Sequence↗
PubMed1998

Mismatch negativity to speech stimuli in 8-month-old infants and adults.

The mismatch negativity (MMN) was measured in 15 normal awake 8-month-old infants and 10 adults to the speech consonants /da/ and /ta/. ERPs were analyzed at 11 electrodes (Fz, Cz, Pz, C3, C4, T3, T4, T5, T6, P3, P4). Four-hundred trials were presented: the /da/ standards with 80% probability and the /ta/ deviants with 20% probability. The ISI was 600 ms. An MMN was observed for both adults and infants but with different scalp distributions. A clear infant MMN was observed only at C3 and T3 electrodes, whereas the adult MMN was present at Fz, Cz, C3, C4 and Pz. A repeated-measures ANOVA on the normalized summed area between 200 and 250 ms revealed an age (adult vs. infant) x electrode interaction. Paired t-tests indicated that adults and infants showed significant differences at the C3, Cz, T3, Pz and T6 electrodes. The adult MMN was largest at Cz and C3 whereas the infant MMN was largest at T3. These data are discussed in terms of possible maturational changes in the MMN.

Adult↗
PubMed1998

Subcortical somatosensory evoked potentials after median nerve stimulation in children.

We report our normative data of subcortical somatosensory evoked potentials (SEPs) after median nerve stimulation from a group of 55 children 4-15 years of age and 18 young adults 18-29 years of age. We recorded near-field potentials from the brachial plexus, the cervical cord and the somatosensory cortex. The far-field potentials P13, P14 and N18 from the brainstem were recorded from the scalp electrodes, when a non-cephalic reference at the contralateral Erb's point or an ear reference was used. The N9 (brachial plexus), N13a (dorsal horn), P13 (caudal medulla oblongata), N18 (medulla oblongata) and N20 (somatosensory cortex) were present in all subjects. The N13b (dorsal column near the foramen magnum or cuneate nucleus) was observed in all children and in 16 adults, P14 (medial lemniscus) in 52 children and 17 adults. The median nerve SEPs provide reliable information about the function of the somatosensory pathway from the upper limb. The subcortical median nerve SEPs should be particularly useful to detect lesions of the upper cervical cord and the cervicomedullary junction. The subcortical SEPs remain unchanged during sleep and facilitate reliable SEP recordings, when sedation is necessary in infants and children.

Adolescent↗
PubMed1998

Somatosensory evoked potentials after posterior tibial nerve stimulation--normative data in children.

We report normative data of somatosensory evoked potentials to posterior tibial nerve stimulation from 47 children 4-15 years of age. We recorded near-field potentials from the peripheral nerve, the cauda equina, the lumbar spinal cord and the somatosensory cortex. Far-field potentials were recorded from the scalp electrodes with a reference at Erb's point and on the earlobe. The near-field potentials N8 (peripheral nerve) and P40 (cortex) were present in all children. N20 (near-field from the cauda equina) was recorded in 38 subjects. N22 (near-field from the lumbar spinal cord), P30 and N37 ( both far-field waveforms probably generated in the brainstem) were recorded in 46 subjects each. The latencies and the peripheral conduction time (N8-N22) increased with age, while the central conduction time (N22-P40) and the intracranial conduction time (P30-P40) both decreased with age (up to about 10 years of age). The spinal conduction time (N22-P30) was relatively independent of age. The interpeak latencies allow the assessment of specific portions of this pathway. The subcortical posterior tibial nerve-somatosensory evoked potentials are of particular interest in children when the cortical peaks are influenced by sedation and sleep, or by anaesthesia.

Adolescent↗
PubMed1998

The efficacy of a pour-on formulation of moxidectin in young red and wapiti-hybrid deer.

AIMS: To measure the efficacy of a pour-on formulation of moxidectin against lungworm and abomasal parasites in weaner wapiti x red deer and to compare this with its efficacy in weaner red deer. METHODS: Six red and six wapiti hybrid deer, naturally infected with lungworm and gastro-intestinal parasites, were treated with pour-on moxidectin at 500 microg/kg body weight and slaughtered 14 or 16 days later, along with six red and six wapiti hybrid untreated control deer. Total worm counts were performed on the lungs, abomasum and abomasal digest of each deer. RESULTS: The efficacy of moxidectin pour-on was 100% against adult and immature lungworms (Dictyocaulus viviparus) in red deer, and 100% and 99.7% effective against adult and immature lungworm in wapiti hybrid deer. The efficacy of moxidectin pour-on was 100, 100, 99.9 and 99.9% respectively against adult, fifth stage, late fourth stage and early fourth stage larvae of Ostertagia-type nematodes (assumed to be Ostertagia, Spiculopteragia, Skrjabinagia and Apteragia spp.) in both red and wapiti hybrid deer. CONCLUSIONS: The pour-on formulation of moxidectin, at 500 microg/kg body weight, is highly effective against mature and immature lungworms and abomasal nematodes in wapiti hybrid deer and equally effective in red deer.

Journal Article↗
PubMed1998

Thermal expansion measurements of frozen biological tissues at cryogenic temperatures.

Thermal expansion data are essential for analyses of cryodestruction associated with thermal stresses during cryopreservation protocols as well as during cryosurgery. The present study tests a commonly used hypothesis that the thermal expansion of frozen tissues is similar to that of pure water ice crystals. This study further provides insight into the potential effect of the presence of cryoprotectants on thermal expansion. A new apparatus for thermal strain measurements of frozen biological tissues within a cryogenic temperature range is presented. Results are presented for fresh tissue samples taken from beef muscle, chicken muscle, rabbit muscle, rabbit bone, and pig liver. Pilot studies of the effect of cryoprotectants on thermal expansion are further presented for rabbit muscle immersed in dimethyl sulphoxide (2 mols/l) and glycerol (2 mols/l), and for pig liver perfused with dimethyl sulphoxide (2 mols/l). Thermal expansion of frozen soft biological tissues was found to be similar to that of water ice crystals in the absence of cryoprotectant. Thermal expansion of the rabbit bone was found to be about one half of that of frozen soft tissues. A significant reduction in the thermal expansion at higher temperatures was observed in the presence of cryoprotectants. A rapid change of thermal strain near -100 degrees C was also observed, which is likely to be associated with the glass transition process of the cryoprotectant solutions.

Animals↗