Biomedical subjects

S Thorpe

Publications and source records attributed to S Thorpe.

34 records · Page 2Linked to original sources

PubMed1988

A cellular analogue of visual cortical plasticity.

Neuronal activity plays an important role in the development of the visual pathway. The modulation of synaptic transmission by temporal correlation between pre- and postsynaptic activity is one mechanism which could underly visual cortical plasticity. We report here that functional changes in single neurons of area 17, analogous to those known to take place during epigenesis of visual cortex, can be induced experimentally during the time of recording. This was done by a differential pairing procedure, during which iontophoresis was used to artificially increase the visual response for a given stimulus, and to decrease (or block) the response for a second stimulus which differed in ocularity or orientation. Long-term modifications in ocular dominance and orientation selectivity were produced in 33% and 43% of recorded cells respectively. Neuronal selectivity was nearly always displaced towards the stimulus paired with the reinforced visual response. The largest changes were obtained at the peak of the critical period in normally reared and visually deprived kittens, but changes were also observed in adults. Our findings support the role of temporal correlation between pre- and postsynaptic activity in the induction of long-lasting modifications of synaptic transmission during development, and in associative learning.

Afferent Pathways↗

PubMed1988

Adjuvant treatment of postmenopausal patients with high risk primary breast cancer. Results from the Danish adjuvant trials DBCG 77 C and DBCG 82 C.

The efficacy of adjuvant treatment with tamoxifen was evaluated in protocol DBCG 77 C. Postmenopausal high risk patients (tumor greater than 5 cm, positive axillary nodes, or invasion to skin/fascia) were randomized after total mastectomy and axillary sampling to postoperative radiotherapy (control) or to radiotherapy plus treatment with tamoxifen (TAM), 30 mg daily for 1 year. A total of 1,716 patients entered the study. At 8 years of follow-up, (7 years median time of observation), we observed a significant increase of recurrence-free survival for the TAM treated group and a reduction in mortality, which is significant for patients less than 70 years of age. Retrospectively, an increased recurrence-free survival in TAM treated patients was significant in the following subgroups: tumor less than 5 cm, positive lymph nodes, anaplasia grade II and estrogen receptor level greater than 100 fmol/mg cytosol protein. In the subsequent trial (DBCG 82 C), 1,347 postmenopausal patients less than 70 years were randomized to one of the following 3 regimens: radiotherapy + tamoxifen, 30 mg daily for 1 year (TAM), TAM alone, or TAM + CMF (CMF i.v. day 1 every 4 weeks x 9). The survival is similar in the 3 groups at 4 years (2 years median time of observation).

Aged↗

PubMed1988

DNA ploidy and S-phase fraction in primary breast carcinomas in relation to prognostic factors and survival for premenopausal patients at high risk for recurrent disease.

Fine needle aspiration on small tumour pieces from 153 premenopausal women with primary breast cancer at high risk for developing recurrent disease has been used for flow cytometric DNA analysis; 133 of the tumours had either one or more cell populations different from diploid or a single, diploid cell population with an aspiration cytology showing presence of typical tumour cells. The distribution of tumour cell populations in this material was rather unusual with a high number of tetraploid populations. There were significant differences between various DNA ploidy classes with respect to prognostic factors such as lymph node involvement and oestrogen and progesterone receptor status. The S-phase fraction was significantly lower for diploid tumour cell populations compared to aneuploid populations. Diploid tumours with high S-phase fraction were not correlated to prognostic factors usually indicating a poor prognosis. Patients with an aneuploid tumour cell population classified as medium aneuploid had a significantly shorter recurrence-free survival than the rest of the patients. No conclusion on the effect of adjuvant treatment for patients with different tumour cell populations can be made at present.

Breast Neoplasms↗

PubMed1987

Altered progesterone/estrogen receptor ratios in endometriosis. A comparative study of steroid receptors and morphology in endometriosis and endometrium.

In a comparative study of endometriosis and endometrium, specimens were taken from both endometriotic and endometrial tissue in 14 patients. Receptor assays and histological examinations were performed on both specimens. Cytosolic estrogen receptors (ERc) as well as cytosolic progesterone receptors (PRc) were detected in 9/14 and 12/12 cases of endometriosis respectively. Nuclear estrogen receptors (ERn) were detected in 4/4 cases of endometriosis. Expressed as fmol/mg cytosol protein, significantly higher values of both ERc and PRc were found in endometrium than endometriosis (p less than 0.01). However, when the ratio between PRc and ERc was considered, significantly higher PRc/ERc ratios were found in the cytosol of endometriotic tissue (p less than 0.01). Thus the lower receptor concentrations found in endometriosis cannot be explained solely as ectopic endometrium being diluted by nonreceptor-containing tissue. In spite of high PRc/ERc ratios in endometriosis, secretory changes similar to those found in endometrium were observed in only one of 7 cases (p less than 0.05).

Adult↗

PubMed1986

Abbott monoclonal enzyme immunoassay measurement of estrogen receptors in human breast cancer: a European multicenter study.

A new enzyme immunoassay (Abbott ER-EIA Monoclonal) for the determination of estrogen receptor in cytosols from breast tumor specimens has been developed by Abbott Laboratories. To establish the correlation of the results from this new technique with currently existing steroid binding methods, a multicenter study was conducted in eight European laboratories. All participants followed the same protocol consisting of a familiarization phase, a proficiency evaluation, and a comparison of existing steroid binding methods with the new immunoassay using panel samples and clinical specimens. ER-EIA was compared with the multipoint dextran coated charcoal assay in six laboratories, four of which followed the EORTC protocol; of the remaining two laboratories, one used a single saturating dose assay, the other an isoelectric focusing assay. The results show no significant difference between reducing agents when used in the ER-EIA. Reproducibility for the immunoassay (interassay coefficient of variation, 6%, interlaboratory coefficient of variation, 11-19%) was somewhat better than that for the steroid binding methods (interlaboratory coefficient of variation, 12-32%). The correlation between the methods was dependent on the origin of the lyophilized specimens. In breast tumor samples, an excellent correlation, (not statistically different from 1) was found between the ER-EIA and the steroid binding method in six laboratories. One laboratory showed a slope of 1.1 for the correlation line; the laboratory using isoelectric focusing showed a slope of 1.9. The mean value determined by the enzyme immunoassay in premenopausal women was 74 fmol/mg cytosol protein, and in postmenopausal women it was 187 fmol/mg cytosol protein with no significant difference in the slope of the correlation line. Results suggest the usefulness of the new standardized enzyme immunoassay for routine use in the clinical laboratory.

Antibodies, Monoclonal↗

PubMed1981

Studies in vivo of the tissue uptake, cellular distribution and catabolic turnover of exogenous glucocerebrosidase in rat.

The kinetics of plasma clearance of highly purified human placental glucocerebrosidase in rats were biphasic with 75% of the infused dose showing a rapid clearance (t1/2 = 11 min) and the remaining 25% a considerably lower rate (t1/2 = 60 min). The majority of the enzyme (60%) was taken up by the liver. Although saturation kinetics for the clearance or uptake were not observed, the very high hepatic endocytic index (217 microliter/min) of glucocerebrosidase uptake indicated that liver uptake was mediated by an adsorptive endocytic process. Analysis of the cellular distribution of recovered glucocerebrosidase revealed predominantly parenchymal cell uptake with 38% of the exogenous enzyme in hepatocytes and only 2% in sinusoidal cells. High-mannose glycoproteins blocked hepatocyte and sinusoidal cell uptake of glucocerebrosidase equally. Kinetic experiments failed to demonstrate a transfer or shuttle of exogenous glucocerebrosidase from sinusoidal cells to hepatocytes. The possibility was raised that uptake of enzyme by the liver may be mediated by a common receptor that functions in both hepatocytes and sinusoidal cells. The catabolic turnover of exogenous glucocerebrosidase in rat liver was biphasic and the rate of decline was similar in hepatocytes and sinusoidal cells.

Animals↗

PubMed1981

Non-enzymatic glucosylation of fibrinogen.

Glucose, when incubated with fibrinogen, binds covalently to that protein. The reaction is non-enzymatic in type and is directly dependant on the time of incubation, temperature and pH. Glucosylation of fibrinogen is not altered by preincubation with aspirin. No preferential glucosylation of fibrinogen, fibrinogen chains or plasmin digestion products XYDE could be demonstrated, suggesting that glucose binding occur at several different sites. No abnormality of thrombin clotting or stability of glucosylated fibrinogen could be detected. These findings are discussed in relation to the previously described abnormalities of fibrinogen metabolism in diabetes mellitus.

Albumins↗

PubMedDate not supplied

Recanalization of tube overgrowth: a useful new indication for laser in palliation of malignant dysphagia.

Overgrowth of an esophageal prosthesis by cancer is a late complication of insertion which presents a difficult management problem. We have treated 14 such patients; 9 had Celestin tubes and 5 Atkinson tubes in situ for a median of 7 months. The median patient age was 75 years; 3 had squamous cell carcinomas and 11 adenocarcinomas; 12 were at the lowest thoracic esophagus or cardia, and 2 were anastomotic. Eleven tubes were overgrown at the top, two at the bottom only, and one at both ends. Dysphagia was graded from 0 to 4 (0 = normal; 4 = dysphagia for liquids). All patients but one improved with treatment. The median pre-treatment grade was 4 (range, 2 to 4) and post-treatment was 2 (0 to 3). This improvement was significant (p less than 0.01) Wilcoxon-signal rank). Most patients required only one or two endoscopies. The median survival was 9 weeks from first laser session (range, 3 to 36 weeks). We feel these results justify laser treatment in most patients in whom cancer overgrowth causes blockage of an esophageal prosthesis.

Adenocarcinoma↗

PubMedDate not supplied

Cuffed esophageal prosthesis: a useful device in desperate situations in esophageal malignancy.

Sixteen patients (three groups) underwent endoscopic intubation with cuffed Wilson-Cook esophageal endoprostheses. Group 1 comprised 10 patients with spontaneous esophago-respiratory fistulas due to malignancy. Six primaries were esophageal, three bronchial and one ovarian. One patient could not tolerate a cuffed tube. All other fistulas closed with intubation but two tubes displaced later. Seven patients managed a soft diet after intubation, but two liquids only. Median survival was 4 weeks (range, 0 to 9 weeks). Group 2 comprised three patients with large endoscopic instrumental tears. Two had definite perforations with extensive surgical emphysema. All had satisfactory contrast swallows the day after intubation and were started on semi-solid diets; median survival was 10 weeks (one still alive). Group 3 included three patients with life-threatening arterial bleeding from cancers of the gastric cardia. No further bleeding occurred in any of the three after intubation and two survived for extended periods (15 and 26 weeks). Cuffed tubes are invaluable in these desperate situations and are worth considering for symptomatic relief even when prognosis is short.

Aged↗

PubMedDate not supplied

Changes in concentration of five PCDD/F congeners after cooking beef from treated cattle.

A large piece of meat taken from a single animal, which had been dosed with five selected PCDD/Fs, was prepared and cooked by a selection of different methods; burgers (fried, grilled, barbecued), roasts (cooked using conventional and microwave ovens) and stews (open pan and pressure cooked). For some of the cooking methods, concentration changes, on a whole product basis, were observed between raw and cooked product. However, in all cases these could be explained simply through changes arising from loss of water and elimination of PCDD/Fs with released fat. The total amounts of PCDD/Fs present in the system (including in released fat) remained unchanged. Dietary intake of PCDD/Fs could therefore be reduced by the removal of visible fat from meat before cooking and by discarding any fat released from foods during the cooking process.

Adipose Tissue↗

PubMedDate not supplied

Concentration changes for 5 PCDD/F congeners after administration in beef cattle.

Ten cattle were treated with daily doses of five PCDD/F congeners, over a 4 week period. Four control animals were not treated. They were subsequently slaughtered as three groups, at 5, 18 and 31 weeks after the first dose. All congeners showed an increase in concentration within animal tissues when sampled at 5 weeks post-dosing. Concentrations had reduced after 18 weeks and there was a further small reduction after 31 weeks. Halflives for each congener were calculated at 13-21 weeks (93-148 days). Concentrations of congeners were different in the various tissues analysed. At 5 weeks after dosing commenced, concentrations in sub-cutaneous fat and in perirenal fat were close to 40 ng/kg (a predicted level based on 50% absorption of the dosed compounds). Concentrations on a fat basis in muscle tissue and liver were, however, about 5 and 10 times higher, respectively. The concentrations found in muscle tissue and liver samples taken at 18 and 31 weeks were approximately twice that found in fat deposits, thus the differences were still apparent, but at a reduced level. It is possible that the distribution phase was incomplete and that PCDD/Fs remained predominantly in association with circulating blood lipids rather than in equilibrium with depot fat. It follows that if livestock were recently exposed to PCDD/Fs (for example, through the consumption of contaminated feed), the analysis of depot fats would not necessarily provide a reliable indicator of the concentrations of PCDD/Fs in edible tissues.

Absorption↗

PubMedDate not supplied

Time trends in human dietary exposure to PCDDs, PCDFs and PCBs in the UK.

Total Diet Study samples collected in 1982 and 1992 were analysed. Estimated dietary intakes of PCDDs, PCDFs and PCBs by UK consumers were found to have fallen substantially during this period and are now considerably below the Tolerable Daily Intake (TDI). Composite samples of human milk were also analysed for PCDDs, PCDFs and PCBs. Estimated combined dietary intakes of PCDDs, PCDFs and PCBs by breast fed infants in 1993-94 via breast milk fell from 170 pg TEQ/kg bodyweight/day at 2 months to 39 pg TEQ/kg bodyweight/day at 10 months.

Adolescent↗

PubMedDate not supplied

Rate coding versus temporal order coding: a theoretical approach.

The belief that neurones transmit information in the form of a firing rate code is almost universal. However, we argue that at least in some situations, the efficiency of a coding strategy based on rate coding is surprisingly poor. A simple mathematical analysis reveals that, due to the stochastic nature of spike generation, even transmitting the simplest signals reliably would require either: (1) excessively long observation periods incompatible with the speed of sensory processing or (2) excessively large numbers of redundant neurones, incompatible with the anatomical constraints imposed by sensory pathways. We argue that such problems may be avoided by using alternative temporal codes which rely on the asynchrony of firing across a population of afferent neurones.

Action Potentials↗

PubMedDate not supplied

Face processing using one spike per neurone.

The speed with which neurones in the monkey temporal lobe can respond selectively to the presence of a face implies that processing may be possible using only one spike per neurone, a finding that is problematic for conventional rate coding models that need at least two spikes to estimate interspike interval. One way of avoiding this problem uses the fact that integrate-and-fire neurones will tend to fire at different times, with the most strongly activated neurones firing first (Thorpe, 1990, Parallel Processing in Neural Systems). Under such conditions, processing can be performed by using the order in which cells in a particular layer fire as a code. To test this idea, we have explored a range of architectures using SpikeNET (Thorpe and Gautrais, 1997, Neural Information Processing Systems, 9), a simulator designed for modelling large populations of integrate-and-fire neurones. One such network used a simple four-layer feed-forward architecture to detect and localise the presence of human faces in natural images. Performance of the model was tested with a large range of grey-scale images of faces and other objects and was found to be remarkably good by comparison with more classic image processing techniques. The most remarkable feature of these results is that they were obtained using a purely feed-forward neural network in which none of the neurones fired more than one spike (thus ruling out conventional rate coding mechanisms). It thus appears that the combination of asynchronous spike propagation and rank order coding may provide an important key to understanding how the nervous system can achieve such a huge amount of processing in so little time.

Action Potentials↗

PubMedDate not supplied

Spike-based strategies for rapid processing.

Most experimental and theoretical studies of brain function assume that neurons transmit information as a rate code, but recent studies on the speed of visual processing impose temporal constraints that appear incompatible with such a coding scheme. Other coding schemes that use the pattern of spikes across a population a neurons may be much more efficient. For example, since strongly activated neurons tend to fire first, one can use the order of firing as a code. We argue that Rank Order Coding is not only very efficient, but also easy to implement in biological hardware: neurons can be made sensitive to the order of activation of their inputs by including a feed-forward shunting inhibition mechanism that progressively desensitizes the neuronal population during a wave of afferent activity. In such a case, maximum activation will only be produced when the afferent inputs are activated in the order of their synaptic weights.

Action Potentials↗

PubMedDate not supplied

Dynamics of orientation coding in area V1 of the awake primate.

To investigate the importance of feedback loops in visual information processing, we have analyzed the dynamic aspects of neuronal responses to oriented gratings in cortical area V1 of the awake primate. If recurrent feedback is important in generating orientation selectivity, the initial part of the neuronal response should be relatively poorly selective, and full orientation selectivity should only appear after a delay. Thus, by examining the dynamics of the neuronal responses it should be possible to assess the importance of feedback processes in the development of orientation selectivity. The results were base on a sample of 259 cells recorded in two monkeys, of which 89% were visually responsive. Of these, approximately two-thirds were orientation selective. Response latency varied considerably between neurons, ranging from a minimum of 41 ms to over 150 ms, although most had latencies of 50-70 ms. Orientation tuning (defined as the bandwidth at half-height) ranged from 16 deg to over 90 deg, with a mean value of around 55 deg. By examining the selectivity of these different neurons by 10-ms time slices, starting at the onset of the neuronal response, we found that the orientation selectivity of virtually every neuron was fully developed at the very start of the neuronal response. Indeed, many neurons showed a marked tendency to respond at somewhat longer latencies to stimuli that were nonoptimally oriented, with the result that orientation selectivity was highest at the very start of the neuronal response. Furthermore, there was no evidence that the neurons with the shortest onset latencies were less selective. Such evidence is inconsistent with the hypothesis that recurrent intracortical feedback plays an important role in the generation of orientation selectivity. Instead, we suggest that orientation selectivity is primarily generated using feedforward mechanisms, including feedforward inhibition. Such a strategy has the advantage of allowing orientation to be computed rapidly, and avoids the initially poorly selective neuronal responses that characterize processing involving recurrent loops.

Animals↗