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Biomedical subjects

D Scott

Publications and source records attributed to D Scott.

At least 199 records · Page 11Linked to original sources
PubMed1995

B7-mediated costimulation can either provoke or prevent clinical manifestations of experimental allergic encephalomyelitis.

T-cell activation requires signalling provided by ligation of the T-cell receptor for antigen (TCR) and a second antigen (Ag) nonspecific signal, known as costimulation. The B7 receptors, CD80 (B7-1) and CD86 (B7-2), on the Ag-presenting cell (APC), interact with T-cell CD28 or CTLA-4 to deliver a costimulatory signal, which is particularly important for Th1 activation. Experimental allergic encephalomyelitis (EAE) is an autoimmune disorder, induced by Th1 cells directed against myelin antigens that provides an in vivo model for studying the role of B7-mediated costimulation in the induction of a pathological immune response. Using a soluble fusion protein ligand for the B7 receptors, as well as specific monoclonal antibodies specific for either CD80 or CD86, it has been demonstrated that B7 costimulation plays a prominent role in determining clinical disease outcome in EAE. Here we review recent data indicating that a paradoxical exacerbation of disease as well as the expected amelioration of disease can occur with costimulatory receptor blockade.

Abatacept↗
PubMed1995

A probability vector and transition matrix analysis of eye movements during visual search.

This report describes a new method for analysing eye movement records during free viewing. The proposed new measures originate from a categorisation of saccade directions. The proportion of each categorised direction and the transition matrix of each two successive categorised directions are then calculated. These new measures are proposed as objective indicators of the strategies employed by an observer engaged in a visual search task. It is concluded that the probability vector and transition matrix analysis are particularly suitable as measures of observer strategies in relation to performance on VDU-based tasks. The relation between these measures and other measures related to search efficiency are also discussed.

Attention↗
PubMed1995

Turnover of the gastric H+,K(+)-adenosine triphosphatase alpha subunit and its effect on inhibition of rat gastric acid secretion.

BACKGROUND & AIMS: The rate of turnover and the effect of inhibition of acid secretion on the turnover of gastric H+,K(+)-adenosine triphosphatase (ATPase) is unknown. The aim of this study was to determine the turnover of the alpha subunit of gastric H+,K(+)-ATPase in rats under control conditions and during inhibition of acid secretion by ranitidine or omeprazole. METHODS: The turnover of the alpha subunit of the ATPase was determined by measuring the loss of incorporated 35S-methionine. This was compared with the rate of recovery of K(+)-stimulated ATPase activity in the omeprazole-treated animals. RESULTS: The half-life of the alpha subunit was 54 hours. A 1-week treatment with omeprazole had no significant effect, but the half-life increased to 125 hours (P < 0.01) after continuous ranitidine infusion. After omeprazole treatment, K(+)-stimulated ATPase activity recovered with a half-time of 15 hours. CONCLUSIONS: The turnover of the gastric ATPase subunit was independent of omeprazole inhibition but was prolonged by ranitidine. The effect of ranitidine suggests that the resting pump in tubulovesicles may turn over more slowly than the stimulated pump in the secretory canaliculus. The rapid recovery of ATPase activity compared with turnover after omeprazole is caused by both H+,K(+)-ATPase synthesis and loss of covalently bound drug.

Animals↗
PubMed1995

The effect of video games on feelings of aggression.

Fueled by the media, the controversy over whether playing popular arcade/computer games increases aggressiveness has only been compounded by inconsistencies within empirical research. This experiment, conducted with university students in Scotland, was designed to explore some of these inconsistencies. Aggressiveness was manipulated as the independent variable. As dependent variables, the Buss-Durkee Hostility Inventory (Buss & Durkee, 1957) and the Eysenck Personality Questionnaire (EPQ; Eysenck & Eysenck, 1975) were used. There was no linear pattern in aggressive affect change across three games that contained varying levels of violence. Results are discussed in terms of the general lack of support for the commonly held view that playing aggressive computer games causes an individual to feel more aggressive.

Adult↗
PubMed1995

Abnormal radiosensitivity of lymphocytes from breast cancer patients with excessive normal tissue damage after radiotherapy: chromosome aberrations after low dose-rate irradiation.

There is a need for a simple, rapid assay for predicting normal tissue reactions in radiotherapy patients to reduce morbidity in sensitive patients and to allow dose escalation in resistant cases. Towards this goal we have investigated the gamma-ray sensitivity of lymphocytes from 16 breast cancer patients who had shown an exaggerated acute or late radiation reaction ('overreaction') of normal tissues after radiotherapy, using chromosome damage (dicentrics) as the endpoint because of its close relationship with cell killing. The use of a low dose-rate (LDR; 0.31 cGy min-1) was found to be better than a high dose-rate (170 cGy min-1) in discriminating between over-reactors and controls, as predicted (and here confirmed) from previous studies on ataxia-telangiectasia (A-T) homozygotes and heterozygotes. Five of seven patients with excessive early skin reactions (e.g. erythema, moist desquamation) showed abnormal radiosensitivity, manifested either as aberration yields above the control range after LDR exposure or as less sparing than controls. The average LDR yield for early over-reactions was significantly higher than for controls (p = 0.009) and average sparing was less (p = 0.0002). Two of 10 patients with late complications (fibrosis, telangiectasia) had LDR yields above the control range, but the average yield for late over-reactors was not significantly above that of controls. Unexpectedly, two patients (one early, one late reaction) had LDR aberration yields below the control range. Quantitatively our results are consistent with the notion that over-reacting breast cancer patients are carriers of the A-T gene. Pilot studies on controls showed that the sparing effect of LDR irradiation was increased by lowering the dose-rate to 0.13 cGy min-1 and by using micronuclei rather than metaphase damage as the endpoint. These modifications to the protocol will be used in a large-scale prospective study.

Adult↗
PubMed1995

A comparison of the radiosensitivity of lymphocytes from normal donors, cancer patients, individuals with ataxia-telangiectasia (A-T) and A-T heterozygotes.

The aim was to determine whether peripheral blood lymphocytes can be used retrospectively to detect hypersensitivity to radiation in breast cancer patients who had exhibited severe reactions to radiotherapy. Blood samples were obtained from patients who developed both acute and late complications. For comparison, samples were also taken from a group of normal individuals, ataxia-telangiectasia (A-T) patients, A-T gene carriers and breast cancer patients previously treated with radiotherapy who failed to develop treatment-related complications. Radiosensitivity was assessed using a limiting dilution clonogenic assay following both high (HDR) and low (LDR) dose-rate irradiation. Following HDR irradiation, only lymphocytes from individuals with A-T were significantly more radiosensitive than those from normal donors. In contrast, at LDR, lymphocytes from A-T heterozygotes and breast cancer over reactors were also, on average, more sensitive than those from normal donors. Lymphocytes from breast cancer patients treated with radiotherapy without developing complications showed no significant differences in radiosensitivity compared with normals. This work has shown that peripheral blood lymphocytes from cancer patients who suffered severe reaction to radiotherapy are, on average, more radiosensitive than those from normal donors, and suggests that lymphocytes may be useful in the future for the development of rapid predictive assays for normal tissue tolerance to radiotherapy.

Ataxia Telangiectasia↗
PubMed1995

Fracture blister formation: a laboratory study.

A biomechanical study was performed to examine a proposed mechanism of fracture blister formation. Sixty cadaver ankle skin specimens were subjected to several levels of uniaxial strain and examined histologically. Dermal-epidermal separation patterns similar to those found histologically in previous studies of biopsied fracture blisters were seen in specimens strained 152% and greater. These findings support the hypothesis that fracture blisters can result from strain developed in the skin during initial fracture deformation.

Biomechanical Phenomena↗
PubMed1995

Retinoblastoma in association with the chromosome breakage syndromes Fanconi's anaemia and Bloom's syndrome: clinical and cytogenetic findings.

Two children presenting with sporadic unilateral retinoblastoma and exhibiting a high degree of chromosome breakage were noted to have unusual facies, microcephaly and abnormal skin pigmentation. In the first child the pattern of both spontaneous and mitomycin-C-induced chromosome breakage was characteristic of Fanconi's anaemia although the degree of breakage was extreme. She also exhibited a striking increase in X-ray-induced chromosomal damage in G0 lymphocytes as measured by dicentric formation and increase in chromatid-type aberrations. She had a number of typical clinical features, including cafe-au-lait patches and abnormalities involving the kidney; however, she demonstrated neither the hypoplasia of radius and thumb nor the typical aplastic phase of this disorder. At age 22 months the child became anaemic with trilineage myelodysplasia, which was rapidly followed by the development of acute myeloblastic leukaemia. The early onset (at age 4 months) of retinoblastoma may have been associated with the underlying genomic instability. The second child exhibited a pattern of chromosome breakage characteristic of Bloom's syndrome, in addition to a moderate increase in damage induced by mytomycin-C. She had the typical stunted growth and malar hypoplasia of Bloom's syndrome although she did not demonstrate the frequently described erythematous 'butterfly rash' Although patients with Fanconi's anaemia and Bloom's syndrome are recognised to be at an increased risk of cancer, retinoblastoma has not previously been described in patients with either condition. We suggest that underlying recessive chromosome breakage syndromes may be underdiagnosed in paediatric cancer patients, with important implications for prognosis and genetic counselling.

Bloom Syndrome↗
PubMed1995

Assessment of a specimen mount for biopsy of impalpable breast lesions.

Biopsy of the impalpable breast lesion is an increasing part of the surgical workload as a result of the National Breast Cancer Screening Programme. A specimen mount card has been described to orientate such specimens in three dimensions prior to radiological and pathological examination. Experience with 243 biopsies in this unit has shown it to be a useful aid in determining completeness of excision. It may also be used as a guide to further surgery when excision is incomplete and breast conservation is the treatment option of choice.

Biopsy↗
PubMed1994

Deletion mapping by immunoselection against the H-Y histocompatibility antigen further resolves the Sxra region of the mouse Y chromosome and reveals complexity of the Hya locus.

A genetic map of the mammalian Y chromosome cannot be produced by standard Mendelian methods because the Y does not participate in meiotic exchange over the majority of its length. However, deletion mapping of the mouse Y chromosome is facilitated by the fact that its short arm carries the histocompatibility-Y (Hya) locus. This locus encodes male-specific (H-Y) antigens that can be selected against in tissue culture by the technique of immunoselection. To produce cells carrying deletions, cytotoxic T lymphocytes (CTLs) specific for H-Y antigens were cocultured with a lymphoblastoid cell line derived from a mouse carrying the portion of the short arm defined by the Sxra translocation on the distal end of its X chromosome. H-Y antigen-loss variant cells that contained Y-specific deletions were identified. Molecular, karyotypic, and immunological analysis of the deletion variants allowed us to define up to 16 ordered intervals and suggested an overall organization of Sxra. The analysis also suggests that at least two and up to five distinct loci encode H-Y antigens.

Animals↗
PubMed1994

Ethnic differences in diabetes knowledge and education: the South Auckland Diabetes Survey.

AIM: To compare the knowledge of diabetes, and diabetes education provision/preferences among European, Maori and Pacific Islands diabetic patients in south Auckland. METHOD: The 331 European, 86 Maori and 123 Pacific Islands patients who were interviewed attended local diabetes services and a stratified subsample of general practitioners. Interviews included closed and open questions of diabetes knowledge, age, sex, diabetes treatment, employment status, weekly household income, school/further education received and the actual and preferred format of diabetes education. RESULTS: Pacific Islands patients knew least, and Europeans most, about diabetes from both open and closed diabetes knowledge questions. The majority of Pacific Islands patients could not name the nature, symptoms or complications of diabetes. This was unaffected by duration of diabetes, place of birth or time in New Zealand, although insulin treated Pacific Islands patients knew more than noninsulin treated patients (closed score 71 SD (4)% vs 61 SD (2)% p < 0.05). Pacific Islands patients were least likely to have received diabetes education (European 69%, Maori 70%, Pacific Islands 49%, p < 0.001). Knowledge scores were higher in those who had received education at diagnosis. Europeans were least likely to want further education (Europeans 52%, Maori 69%, Pacific Islands 63%, p < 0.01). The preferred sources for ongoing education were the lay educator/diabetes nurse specialist service (Europeans 28%, Maori 37%, Pacific Islands 76%), and the hospital based clinic among Europeans (27%) and Maori (36%). No Pacific Islands patients preferred a hospital based ongoing education service, while few diabetic patients of any ethnic group preferred to receive education via their general practitioner. In all ethnic groups, patients wanting more education knew more than those who did not. CONCLUSION: The local delivery of diabetes education is uneven. Among Pacific Islands people, it is grossly inadequate. In order for all patients to receive such education, the diabetes services need to be better coordinated and integrated with primary health care.

Aged↗
PubMed1994

Effects of a change in phosphorus requirement on phosphorus kinetics in the sheep.

An experiment was carried out to examine the effects of a change in P requirement, achieved by intravenous calcium loading, on intestinal phosphorus absorption, salivary phosphorus secretion and faecal endogenous phosphorus loss in adult sheep fitted with a rumen and duodenal cannula. Isotope dilution was used to measure faecal endogenous phosphorus loss while 103ruthenium phenanthroline and 51chromium-ethylenediamine tetra-acetic acid were used to measure duodenal phosphorus flow. The infusion of calcium chloride led to an increase in calcium and phosphorus retention, the increase in phosphorus retention being due to a reduction in faecal phosphorus excretion as a result of enhanced intestinal phosphorus absorption and reduced faecal endogenous phosphorus excretion. There was, however, no change in duodenal phosphorus flow or in the amount of phosphorus estimated to have been added to the digesta via the saliva. These results suggest that the increase in phosphorus retention seen in response to an increase in phosphorus requirement is largely achieved through an increase in intestinal absorptive efficiency and not through any reduction in endogenous phosphorus secretion into the gut.

Animals↗
PubMed1994

A re-evaluation of the cytogenetic effects of styrene.

Results from new chromosome studies in laboratory animals, comparative investigations of styrene metabolism and pharmacokinetics in humans and animals, and several recent cytogenetic surveys of styrene-exposed workers have necessitated a comprehensive re-evaluation of the chromosome-damaging effects of this chemical. Both styrene and its genotoxic metabolite, styrene oxide, can induce chromosome aberrations (CA) and sister chromatid exchanges (SCE) in vitro, but the chromosome-damaging ability of styrene is only manifested if test conditions favour its metabolic activation over inactivation. There is no convincing evidence of styrene clastogenicity in experimental animals. Styrene oxide is clastogenic only at lethal concentrations via i.p. injection in Chinese hamsters (but not via inhalation) or after oral treatment of mice, a route considered inappropriate for investigating the chromosome-damaging potential of inhaled styrene in man. Styrene and styrene oxide can induce SCE in animals at very high concentrations. Eighteen of 52 cytogenetic studies (CA, micronuclei, SCE) on peripheral blood lymphocytes of styrene workers have reported increases in chromosome damage. The positive findings are not compatible with the conclusion that styrene is responsible for the cytogenetic effects for the following reasons. (a) The positive or negative outcome of the various investigations bears no relationship to the degree of exposure of the workers. (b) There is no convincing evidence of a positive dose response relationship. (c) The relative induction of CA and SCE in worker studies are the opposite of observations of styrene effects in cultured lymphocytes and in laboratory animals. (d) The reports of chromosome-type exchanges in some studies of styrene workers is inconsistent with observations of styrene clastogenicity in cultured lymphocytes. (e) Reports of SCE induction in workers exposed to low concentrations of styrene are not compatible with results of animal inhalation studies, particularly in view of the differences in styrene metabolism and pharmacokinetics between humans and rodents. The increases in cytogenetic effects reported in some studies on styrene workers are probably attributable to the presence of other chromosome-damaging agents in the workplace and/or to inadequate investigations.

Animals↗