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Biomedical subjects

L Henderson

Publications and source records attributed to L Henderson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Industrial Genotoxicology Group collaborative trial to investigate cell cycle parameters in human lymphocyte cytogenetics studies.

Human lymphocyte cultures have been used for many years for assessing the in vitro clastogenic potential of test substances. In these assays the harvest time should be based on the cell cycle time in order to ensure that cells are sampled at an appropriate time for the detection of clastogenic effects. The sources of variation in the cell cycle time in routine cytogenetic assays have not been well studied. Consequently 13 laboratories, all members of the Industrial Genotoxicology Group, participated in a collaborative study to measure the variation in cell cycle time in cultured human peripheral blood lymphocytes under various conditions. The study was performed in two phases, spaced 6 months apart. The average generation time (AGT) was measured by the incorporation of bromodeoxyuridine. Very similar AGTs were found in the presence and absence of S9 mix. The mean AGT (mean of four donors) in each laboratory varied from 11.2 to 17.1 h, indicating there is significant variability in cell cycle times of human peripheral blood lymphocytes between laboratories. There was greater variation between laboratories than within laboratories. A comparison of AGT values at 72 h performed in experiments at least 6 months apart indicated good reproducibility in most laboratories. The study indicates that a 24 h post-treatment harvest may result in the analysis of very few first division cells unless very significant cell cycle delay is induced by the test substance. It was also found that a post-harvest time equivalent to 1.5 cell cycles will result in an approximately equal mixture of first and second division cells and therefore should by suitable for assessing both the induction of chromosome aberrations and polyploidy.

Animals↗
PubMed1997

Mean MMPI profile of referrals to a shyness clinic.

Shyness occurs in over 48% of the population, becoming disabling in 13% or more. Clinical observation suggests that individuals seeking treatment for shyness are in significantly greater distress than the general population, showing greater depression, generalized anxiety, social avoidance, interpersonal sensitivity, and shame, than is indicated by earlier studies. We gave the MMPI to 25 men and 20 women referred for problems with shyness to assess our observations. Analysis confirmed the hypotheses. Men scored higher than women in a slightly different profile configuration.

Adolescent↗
PubMed1996

Extended harvest times are not necessary for the detection of in vitro clastogens in regulatory cytogenetics studies.

The choice of harvest time in in vitro cytogenetics assays is a critical factor in determining the sensitivity of the assay for detecting clastogenic potential. As yet there is no harmonization of regulatory requirements in this aspect. It has been suggested that the use of extended harvest times can improve the sensitivity of detecting some chemicals which either induce cell cycle delay or produce lesions which induce chromosome aberrations at divisions subsequent to the first post-treatment mitosis. The incidence of such chemicals encountered in the routine testing of chemicals for regulatory submissions is not known. Therefore a large database of 550 chemicals tested in nine laboratories using standard regulatory protocols, including a late harvest time, was assessed for the incidence of chemicals uniquely positive only at a delayed harvest time. The number of such chemicals was very low ( < 0.2%) and the chromosome damage induced by these chemicals may not result from direct genotoxic mechanisms. Based on these data it is recommended that there is no need to include an extended harvest time in in vitro cytogenetics assays except where it might help to resolve an equivocal result.

Animals↗
PubMed1996

Counting and cardinality in English nursery pupils.

This study examines the development of counting and cardinality in a structured sample of 60 English 3 1/2-4 1/2 year-olds attending local education authority nursery classes in socially mixed areas of Portsmouth. Children were given two types of task: counting sets of animals, and giving specified numbers of items from a pile. Three measures of cardinal understanding were used: spontaneous repetition of the last word on completion of a counting trial, repetition of the last word in reply to a question, and use of counting vs. grabbing when asked to give a specific number of items from a heap. In line with research on other populations the results indicate a pronounced developmental discrepancy between procedural and conceptual knowledge of counting, but cardinality appears to develop six months later in this population than in other populations studied. There were marked individual differences, however. Proficiency with object counting was found to be necessary, but not sufficient, for cardinal understanding. Children rarely repeated final count words spontaneously. Last word repetition in response to a verbal prompt depended on the nature of the prompt. Contrary to previous research, the present results indicate that last word repetition elicited by the prompt 'how many?' is not merely a conventional reply but generally implies an understanding of cardinality. The findings also indicate that an understanding of cardinality emerges relatively suddenly, consistent with the discovery or construction of a principle. Whether nursery pupils treat counting simply as a conventional routine without cardinal significance appears to depend on the situation as well as on their understanding of cardinality. The findings are discussed in relation to Karmiloff-Smith's Representational Redescription model.

Analysis of Variance↗
PubMed1996

Inhibition of brain P-450 arachidonic acid epoxygenase decreases baseline cerebral blood flow.

Arachidonic acid (AA) is metabolized by the cytochrome P-450 (P-450) epoxygenase pathway to epoxyeicosatrienoic acids (EETs) in the brain parenchymal tissue and perivascular astrocytes. EETs dilate cerebral microvessels and enhance K+ current in cerebrovascular smooth muscle cells. In the current study, the effect of a subdural administration of miconazole, an inhibitor of P-450 epoxygenase, on microvascular perfusion of rat cerebral cortex was evaluated using laser-Doppler flowmetry (LDF) Baseline cerebral blood flow (CBF) decreased by 29.7 +/- 7.3% (n = 5) after administration of 20 microM miconazole into the subdural space for 30 min. Responses of CBF to sodium nitroprusside and 5-hydroxytryptamine were unaltered by miconazole treatment. Administration of vehicle alone in time-control experiments had no effect on CBF. In other experiments, the effects of miconazole on the metabolism of [14C]AA by cultured rat astrocytes and on nitric oxide synthase activity in homogenates of rat brain were examined. Miconazole inhibited conversion of AA to EETs by cultured astrocytes but had no effect on the conversion of L-arginine to L-citrulline by homogenates of rat brain. These results implicate endogenous P-450 epoxides of AA in the regulation of basal blood flow in cerebral microcirculation.

Animals↗
PubMed1996

Public perceptions of brain tumours in Scotland: the need for access to appropriate information.

The aim of the study was to evaluate knowledge and perceptions of brain tumours in a heterogeneous, highly educated group of adults living in Edinburgh. Two hundred and forty four respondents answered a questionnaire about the causes, effects and treatments of brain tumours. There were misconceptions about several clinical and biological aspects of intracranial tumours although most respondents were aware of the bleak prognosis associated with many neoplasms. These results, from the intellectual elite of Scotland's capital, suggest that access to information about brain tumours should be readily available. Five leaflets, covering various aspects of brain tumours, that are available through the recently established Scottish charity Brain Tumour Action seem well formulated to address areas of concern and misconception.

Adult↗
PubMed1995

The functional anatomy of remembered saccades: a PET study.

Studies of patients with damage to the dorsolateral prefrontal cortex (DLPFC) and the basal ganglia have shown that these areas are involved in the control of remembered saccades. However, although positron emission tomography (PET) studies of remembered saccades have demonstrated extensive cortical and subcortical activation, they have failed to detect any significant increase in regional cerebral blood flow (rCBF) in these areas. This study was designed to see if these areas could be activated. Eight right-handed male volunteers were studied using H2(15)O PET. Comparison of the rCBF in the remembered saccade task to a rest control state revealed significant activation in both the DLPFC and the basal ganglia, and also the frontal eye fields, the supplementary motor area, the posterior parietal lobe, the cingulate cortex, the striate cortex, the extrastriate cortex and the superior temporal lobe. These findings confirm that remembered saccades are controlled by an extensive cortical and subcortical network, which includes the DLPFC and the basal ganglia.

Adult↗
PubMed1995

Oculomotor function in amyotrophic lateral sclerosis: evidence for frontal impairment.

Saccadic eye movements, fixation, and smooth pursuit were recorded in 17 subjects with amyotrophic lateral sclerosis (ALS) and 11 age-matched controls using a magnetic scleral search coil. Reflexive, remembered and antisaccades, and smooth pursuit at four target velocities were studied. Subjects with ALS showed significantly elevated error rates (distractibility) and latency in the antisaccade and remembered saccade paradigms but no abnormality of reflexive saccades. The frequency of small saccades that intruded on steady fixation (square-wave jerks) was also increased in ALS subjects. Peak velocity gain of smooth pursuit and performance on the Wisconsin Card Sort Test did not differ significantly between the two groups. These findings are consistent with prefrontal dysfunction in ALS and provide an independent source of support for the thesis that the pathology of this condition invades frontal cortex.

Adult↗
PubMed1995

The internal control of action and Parkinson's disease: a kinematic analysis of visually-guided and memory-guided prehension movements.

This paper reports two experiments which examined the effects of Parkinson's disease (PD) upon the sensorimotor mechanisms used to control prehension movements. Transport and grasp kinematics for visually-guided and memory-guided prehension movements were examined in healthy control subjects and compared against those of patients with idiopathic PD. Two research questions were addressed: (1) Are patients with PD particularly susceptible to distraction by non-relevant objects? (2) Are patients with PD especially reliant on external feedback when executing goal-directed actions? The results indicated that the patient group were no more susceptible to distraction by non-relevant objects than the control group. In contrast, the patients with PD were shown to be significantly impaired when executing memory-guided reaches. Furthermore, the deficits exhibited by the PD group on memory-guided reaches were confined solely to those markers associated with the transport component of the prehension movement. That is, while both controls and patients with PD widened their grip aperture on memory-guided trials, the magnitude of this adjustment was comparable across the two groups. The implications of these findings for theories of visuomotor processing in sufferers of PD and the control of prehension movements more generally are discussed.

Aged↗
PubMed1995

Serial reaction time learning and Parkinson's disease: evidence for a procedural learning deficit.

This paper presents evidence in support of a serial reaction time (SRT) deficit associated with Parkinson's disease, and related to the acquisition or execution of serial-order information. Eleven patients with idiopathic Parkinson's disease, and 10 age-matched but otherwise healthy control subjects, were compared on a variant of the SRT task introduced by Nissen and Bullemer (Cognit. Psychol. 19, 1-32, 1987). The results of this study clearly demonstrate that PD patients produce a quite different pattern of RT performance to that of control subjects. Such a pattern of results may reflect either: (1) a deficit in the patients' ability to learn the temporal order information provided by a repeating sequence of target locations in the SRT task; or (2) a deficit in the patients' ability to express temporal order information provided by the repeating sequence of target locations in the SRT task.

Aged↗
PubMed1995

A Project Alpha program for smaller chapters.

Smaller chapters cannot easily adapt to their groups the projects of larger chapters or programs at the national level. To address this problem, the Coosa Valley chapter of AORN, Rome, Ga, developed a program that offers perioperative experience to nursing students at a local college. Members of the chapter act as preceptors for the students and educate them before the students' preceptorships in the OR. This education seems to relieve some of the intimidation and fear related to the OR, and students in the program are more willing to participate in the program.

Curriculum↗
PubMed1995

Saccadic abnormalities in psychotic patients. I. Neuroleptic-free psychotic patients.

Most of the previous research reporting abnormalities of rapid re-fixation eye movements (saccades) in patients with schizophrenia has used patients receiving neuroleptic medication. In this study non-neuroleptically medicated schizophrenics were compared with other psychiatric patients using a variety of saccadic paradigms to determine the specificity of saccadic dysfunction. The patient groups consisted of schizophrenics (N = 18), bipolar affectives (N = 18), anxiety neurotics (N = 10) and normal controls (N = 31), none of whom had received neuroleptic medication for the preceding 6 months. Four behavioural paradigms, reflexive, predictive, remembered and ANTI were used to elicit saccades. The primary abnormality in the schizophrenic group was a significantly increased rate of distractibility in the ANTI (saccades made towards the target rather than in an opposite direction) and REM (saccades made prior to the imperative cue) paradigms. The major neuropsychological variable predictive of these errors was Wisconsin card sort perseverative errors. These data, in conjunction with findings from previous neurological research, would seem to provide converging evidence towards dysfunction of prefrontal cortex in schizophrenia.

Adult↗
PubMed1995

Saccadic abnormalities in psychotic patients. II. The role of neuroleptic treatment.

The effects of dopamine-antagonistic neuroleptic (NL) medication on saccadic eye movements were compared in matched groups of 40 NL-treated and 18 NL-free schizophrenic patients and in 18 NL-treated and 14 NL-free bipolar affective patients. Manipulation of the saccadic paradigm yielded data on four types of saccade: those reflexively elicited by novel stimuli (REFLEX saccades), those directed towards the remembered location of a target now extinguished (REM) or towards the location where a predictably alternating target is expected to appear (PRED), or ANTI saccades, directed away from the stimulus to the mirror image location. Extensive psychiatric, neurological and neuropsychological assessments were also carried out on all subjects. The saccades of NL-treated patients, regardless of diagnosis, were less spatially accurate than those of NL-free patients, with a greater tendency to fall short of the target when generated towards the locus of a mentally represented target. This effect was greatest with a predictably alternating target, especially during periods when target visibility was withdrawn, only a temporal cue remaining. This pattern of impairment which is also found in early stages of Parkinson's disease is likely to be due to deficiency of striatal dopamine. Its best clinical predictors were disease duration, and Webster-Parkinsonism scores. Failure to suppress reflexive saccades to the stimulus in the REM and ANTI paradigms were more closely associated with schizophrenia than with NL treatment and were best predicted by negative symptoms and Wisconsin perseverative errors, both of which are widely regarded as indicators of frontal lobe dysfunction.

Adult↗
PubMed1995

Adaptation of nicotinic acetylcholine receptor, myogenin, and MRF4 gene expression to long-term muscle denervation.

Muscle activity alters the expression of functionally distinct nicotinic acetylcholine receptors (nAChR) via regulation of subunit gene expression. Denervation increases the expression of all subunit genes and promotes the expression of embryonic-type (alpha 2 beta delta gamma) nAChRs, while electrical stimulation of denervated muscle prevents this induction. We have discovered that the denervation-induced increases in alpha, beta, gamma, and delta subunit gene expression do not persist in muscles that have been denervated for periods extending beyond a couple of months. However, expression of RNA encoding the epsilon-subunit remains elevated suggesting a return to expression of predominantly adult-type (alpha 2 beta delta epsilon) nAChR in long-term denervated muscles; a finding confirmed by single channel patch-clamp analysis. Since the nAChR subunit genes are regulated by the MyoD family of muscle regulatory factors, and the genes encoding these factors are also induced following short-term muscle denervation, we determined their level of expression in long-term denervated muscle. Although MyoD and myf-5 RNA levels remained elevated, myogenin and MRF4 RNAs were induced only transiently by muscle denervation. Surprisingly, Id-1, a negative regulator of transcription, was gradually induced in denervated muscle with RNA levels peaking about two months after denervation. It is likely that this maintained level of increased Id expression, in conjunction with the returning levels of myogenin and MRF4 expression, account for the reduced level of embryonic receptors in long-term denervated muscle. These changing patterns of gene expression may have important consequences for the ability of muscle to recover function after denervation.

Adaptation, Physiological↗
PubMed1995

Procedures for the detection of chemically induced aneuploidy: recommendations of a UK Environmental Mutagen Society working group.

The development of assays to detect numerical chromosome aberrations has not kept pace with that for assays used to detect other genotoxicity endpoints such as gene mutations and structural chromosome aberrations, even though the importance of aneuploidy in relation to heritable defects in germ cells and to carcinogenesis in somatic cells is acknowledged. Regulatory bodies at present have no formal requirements concerning aneuploidy detection and decisions are made on a case-by-case basis. The aim of this review is to indicate which assays are available for the detection of chemically induced aneuploidy and what aspects should be taken into account when testing for chemically induced aneuploidy using in vitro, in vivo somatic and in vivo germ cell assays without dictating exact protocols. Our recommendations concentrate on systems that, to date, have been most extensively used and we indicate where future developments may lie. It is important that the currently available and future tests for chemically induced aneuploidy should be adequately validated before being implemented into screening strategies or regulatory guidelines. This requirement has not yet been met and is confounded by the lack of a well defined reference database of animal and human chemical aneugens.

Aneuploidy↗
PubMed1995

Abnormal refractoriness in patients with Parkinson's disease after brief withdrawal of levodopa treatment.

Two pairwise matched groups of patients with mild to moderate Parkinson's disease and a group of normal age matched controls were used to investigate the effects on simple and choice reaction time (RT) of brief withdrawal of levodopa therapy. Comparisons within and across these groups disclosed a selective effect of levodopa withdrawal. After about 12 hours of levodopa deprivation, patients exhibited an exaggeration of normal refractoriness, the well established tendency for RT to increase progressively as the delay between a response and the next imperative signal is reduced below 0.5 s. Increased refractoriness was at least as great for simple as choice RT. Choice RT on trials involving repetition (as opposed to alternation) of the previous response, however, showed no tendency towards greater impairment by brevity of the recovery period or by withdrawal of medication, eliminating an effector based account. With longer recovery periods, RT was unaffected by medication; indeed, unmedicated patients were as fast as normal subjects under these conditions. Even at the briefest delays, fully medicated patients did not differ from normal controls. The paper concludes with a critical review of chronometric studies of medication effects in Parkinson's disease.

Analysis of Variance↗
PubMed1994

Photomutagenicity assays in bacteria: factors affecting assay design and assessment of photomutagenic potential of para-aminobenzoic acid.

Photomutagenicity assays are required for regulatory submissions of some chemicals. As yet there are no well-validated protocols available for these assays. Critical factors which may contribute to the ability of a bacterial assay to detect photomutagens (e.g. dose of UV and test chemical, exposure conditions, light source, bacterial strains) were investigated using two known photomutagens, chlorpromazine and 8-methoxypsoralen. Salmonella typhimurium strains TA98, TA102 and TA1537 and Escherichia coli strains WP2 and WP2(pKM101) were used and differences in the responsiveness of these strains were observed with these substances. Both chemicals were detected using either UV exposure in suspension or on the agar plates. On the basis of these observations and on other results reported in the literature, recommendations are made on protocol aspects for assessing photomutagenic potential in routine screening tests. Using these recommendations the sunscreen para-aminobenzoic acid was tested in S.typhimurium strains TA98, TA100, TA1535, TA1537 and E. coli strains WP2 and WP2 (pKM101), using both plate irradiation and suspension exposure conditions. No evidence of mutagenic potential was detected.

4-Aminobenzoic Acid↗