Showing papers by "University College London published in 1993"
TL;DR: The phase was highly correlated with spatial location and less well correlated with temporal aspects of behavior, such as the time after place field entry, and the characteristics of the phase shift constrain the models that define the construction of place fields.
Abstract: Many complex spike cells in the hippocampus of the freely moving rat have as their primary correlate the animal's location in an environment (place cells). In contrast, the hippocampal electroencephalograph theta pattern of rhythmical waves (7-12 Hz) is better correlated with a class of movements that change the rat's location in an environment. During movement through the place field, the complex spike cells often fire in a bursting pattern with an interburst frequency in the same range as the concurrent electroencephalograph theta. The present study examined the phase of the theta wave at which the place cells fired. It was found that firing consistently began at a particular phase as the rat entered the field but then shifted in a systematic way during traversal of the field, moving progressively forward on each theta cycle. This precession of the phase ranged from 100 degrees to 355 degrees in different cells. The effect appeared to be due to the fact that individual cells had a higher interburst rate than the theta frequency. The phase was highly correlated with spatial location and less well correlated with temporal aspects of behavior, such as the time after place field entry. These results have implications for several aspects of hippocampal function. First, by using the phase relationship as well as the firing rate, place cells can improve the accuracy of place coding. Second, the characteristics of the phase shift constrain the models that define the construction of place fields. Third, the results restrict the temporal and spatial circumstances under which synapses in the hippocampus could be modified.
2,434 citations
TL;DR: Comparisons of distribution of cerebral blood flow in these conditions localized the phonological store to the left supramarginal gyrus whereas the subvocal rehearsal system was associated with Broca's area, the first demonstration of the normal anatomy of the components of the 'articulatory loop'.
Abstract: By repeating words 'in our head', verbal material (such as telephone numbers) can be kept in working memory almost indefinitely. This 'articulatory loop' includes a subvocal rehearsal system and a phonological store. Little is known about neural correlates of this model of verbal short-term memory. We therefore measured regional cerebral blood flow, an index of neuronal activity, in volunteers performing a task engaging both components of the articulatory loop (short-term memory for letters) and a task which engages only the subvocal rehearsal system (rhyming judgement for letters). Stimuli were presented visually and the subjects did not speak. We report here that comparisons of distribution of cerebral blood flow in these conditions localized the phonological store to the left supramarginal gyrus whereas the subvocal rehearsal system was associated with Broca's area. This is, to our knowledge, the first demonstration of the normal anatomy of the components of the 'articulatory loop'.
2,212 citations
TL;DR: It is suggested that eradication of H pylori causes regression of low-grade B-cell gastric MALT lymphoma, and that anti-H-pylori treatment should be given for this lymphoma.
2,095 citations
TL;DR: It is suggested that the evolution of large groups in the human lineage depended on developing a more efficient method for time-sharing the processes of social bonding and that language uniquely fulfills this requirement.
Abstract: Group size is a function of relative neocortical volume in nonhuman primates. Extrapolation from this regression equation yields a predicted group size for modern humans very similar to that of certain hunter-gatherer and traditional horticulturalist societies. Groups of similar size are also found in other large-scale forms of contemporary and historical society. Among primates, the cohesion of groups is maintained by social grooming; the time devoted to social grooming is linearly related to group size among the Old World monkeys and apes. To maintain the stability of the large groups characteristic of humans by grooming alone would place intolerable demands on time budgets. It is suggested that (1) the evolution of large groups in the human lineage depended on the development of a more efficient method for time-sharing the processes of social bonding and that (2) language uniquely fulfills this requirement. Data on the size of conversational and other small interacting groups of humans are in line with the predictions for the relative efficiency of conversation compared to grooming as a bonding process. Analysis of a sample of human conversations shows that about 60% of time is spent gossiping about relationships and personal experiences. It is suggested that language evolved to allow individuals to learn about the behavioural characteristics of other group members more rapidly than is possible by direct observation alone.
1,811 citations
TL;DR: This work has identified missense mutations of the RET proto-oncogene in 20 of 23 apparently distinct MEN 2A families, but not in 23 normal controls, and found that 19 of these 20 mutations affect the same conserved cysteine residue at the boundary of theRET extracellular and transmembrane domains.
Abstract: Multiple endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer syndrome that affects tissues derived from neural ectoderm. It is characterized by medullary thyroid carcinoma (MTC) and phaeochromocytoma. The MEN2A gene has recently been localized by a combination of genetic and physical mapping techniques to a 480-kilobase region in chromosome 10q11.2 (refs 2,3). The DNA segment encompasses the RET proto-oncogene, a receptor tyrosine kinase gene expressed in MTC and phaeochromocytoma and at lower levels in normal human thyroid. This suggested RET as a candidate for the MEN2A gene. We have identified missense mutations of the RET proto-oncogene in 20 of 23 apparently distinct MEN 2A families, but not in 23 normal controls. Further, 19 of these 20 mutations affect the same conserved cysteine residue at the boundary of the RET extracellular and transmembrane domains.
1,810 citations
1,583 citations
TL;DR: This neurotrophic strategy for the regulation of neuronal numbers may be only one example of a general mechanism that helps to regulate the numbers of many other vertebrate cell types, which also require signals from other cells to survive.
Abstract: During the development of the vertebrate nervous system, up to 50 percent or more of many types of neurons normally die soon after they form synaptic connections with their target cells. This massive cell death is thought to reflect the failure of these neurons to obtain adequate amounts of specific neurotrophic factors that are produced by the target cells and that are required for the neurons to survive. This neurotrophic strategy for the regulation of neuronal numbers may be only one example of a general mechanism that helps to regulate the numbers of many other vertebrate cell types, which also require signals from other cells to survive. These survival signals seem to act by suppressing an intrinsic cell suicide program, the protein components of which are apparently expressed constitutively in most cell types.
1,481 citations
1,460 citations
Journal Article•
1,390 citations
TL;DR: Evidence is contained in support of a new ‘configurational’ paradigm in which a primary property of the form of the urban grid is to privilege certain spaces over others for through movement.
Abstract: Existing theories relating patterns of pedestrian and vehicular movement to urban form characterise the problem in terms of flows to and from 'attractor' land uses. This paper contains evidence in support of a new 'configurational' paradigm in which a primary property of the form of the urban grid is to privilege certain spaces over others for through movement In this way it is suggested that the configuration of the urban grid itself is the main generator of patterns of movement. Retail land uses are then located to take advantage of the opportunities offered by the passing trade and may well act as multipliers on the basic pattern of 'natural movement' generated by the grid configuration. The configurational correlates of movement patterns are found to be measures of global properties of the grid with the 'space syntax' measure of 'integration' consistently found to be the most important. This has clear implications for urban design suggesting that if we wish to design for well used urban space, then it is not the local properties of a space that are important in the main but its configurational relations to the larger urban system.
1,326 citations
TL;DR: The actions of muscarinic receptors on the heart, smooth muscle, glands and on neurons (both presynaptic and postsynaptic) in the autonomic nervous system and the central nervous system are analyzed in terms of subtypes, biochemical mechanisms and effects on ion channels, including K+ channels and Ca2+ channels.
TL;DR: P positron emission tomography was used to determine the foci of relative cerebral blood flow increases produced when subjects viewed a moving checkerboard pattern, compared to viewing the same pattern when it was stationary.
Abstract: In pursuing our work on the organization of human visual cortex, we wanted to specify more accurately the position of the visual motion area (area V5) in relation to the sulcal and gyral pattern of the cerebral cortex. We also wanted to determine the intersubject variation of area V5 in terms of position and extent of blood flow change in it, in response to the same task. We therefore used positron emission tomography (PET) to determine the foci of relative cerebral blood flow increases produced when subjects viewed a moving checkerboard pattern, compared to viewing the same pattern when it was stationary. We coregistered the PET images from each subject with images of the same brain obtained by magnetic resonance imaging, thus relating the position of V5 in all 24 hemispheres examined to the individual gyral configuration of the same brains. This approach also enabled us to examine the extent to which results obtained by pooling the PET data from a small group of individuals (e.g., six), chosen at random, would be representative of a much larger sample in determining the mean location of V5 after transformation into Talairach coordinates. After stereotaxic transformation of each individual brain, we found that the position of area V5 can vary by as much as 27 mm in the left hemisphere and 18 mm in the right for the pixel with the highest significance for blood flow change. There is also an intersubject variability in blood flow change within it in response to the same visual task. V5 nevertheless bears a consistent relationship, within each brain, to the sulcal pattern of the occipital lobe. It is situated ventrolaterally, just posterior to the meeting point of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus. In position it corresponds almost precisely with Flechsig's Feld 16, one of the areas that he found to be myelinated at birth. © 1993 Oxford University Press.
TL;DR: It is suggested that stress protein elevation, rather than the nonspecific effects of thermal or ischemic stress, may be responsible for the myocardial protection seen in this model.
Abstract: BACKGROUND To test the hypothesis that the heat shock response is associated with myocardial salvage, the heat stress protein (HSP) content of cardiac tissue was increased by either ischemic or thermal stress. METHODS AND RESULTS Rabbits were divided into four groups. Ischemic pretreatment (n = 15) comprised four 5-minute episodes of coronary ligation separated by 10 minutes of reperfusion. The corresponding control group (n = 21) underwent surgical preparation without coronary ligation. Thermal pretreatment (n = 16) involved whole-body temperature elevation to 42 degrees C for 15 minutes; corresponding controls (n = 15) were treated with anesthetic alone. Twenty-four hours later, hearts were removed for HSP estimation or infarct size assessment after a 30-minute coronary ligation. Myocardial HSP72 content assessed by Western blotting was elevated by both ischemic and thermal pretreatments (2.5 +/- 0.2 units, n = 4, and 2.8 +/- 0.3 units, n = 4, mean +/- SEM; P = NS, respectively) compared with the corresponding control groups (1.0 +/- 0.3, n = 4, P < or = .01 and 0.3 +/- 0.1, n = 4, P < or = .01, respectively). HSP60 was preferentially elevated by ischemic pretreatment. After a 30-minute coronary occlusion and 120 minutes of reperfusion, ischemic and thermal pretreatments limited infarct size as a percentage of the volume at risk by 28.8 +/- 5.2% vs 52.0 +/- 5.2%, P < or = .01 and 32.8 +/- 3.8% vs 56.9 +/- 6.5%, P < or = .01, respectively. CONCLUSIONS Myocardial stress protein induced by either sublethal thermal or ischemic injury is associated with myocardial salvage. Our findings suggest that stress protein elevation, rather than the nonspecific effects of thermal or ischemic stress, may be responsible for the myocardial protection seen in this model. Our observations may have important implications regarding myocardial adaptation to brief periods of ischemia.
TL;DR: A randomised comparison of high-dose chemotherapy plus ABMT with the same drugs at lower doses not requiring bone-marrow rescue in patients with active Hodgkin's disease found that high doses facilitated by ABMT can lead to better disease-free survival.
TL;DR: Weighted averaging regression and calibration form a simple, yet powerful method for reconstructing environmental variables from species assemblages as discussed by the authors, which performs well with noisy, species-rich data that cover a long ecological gradient (>3 SD units).
Abstract: Weighted averaging regression and calibration form a simple, yet powerful method for reconstructing environmental variables from species assemblages. Based on the concepts of niche-space partitioning and ecological optima of species (indicator values), it performs well with noisy, species-rich data that cover a long ecological gradient (>3 SD units). Partial least squares regression is a linear method for multivariate calibration that is popular in chemometrics as a robust alternative to principal component regression. It successively selects linear components so as to maximize predictive power. In this paper the ideas of the two methods are combined. It is shown that the weighted averaging method is a form of partial least squares regression applied to transformed data that uses the first PLS-component only. The new combined method, ast squares, consists of using further components, namely as many as are useful in terms of predictive power. The further components utilize the residual structure in the species data to improve the species parameters (‘optima’) in the final weighted averaging predictor. Simulations show that the new method can give 70% reduction in prediction error in data sets with low noise, but only a small reduction in noisy data sets. In three real data sets of diatom assemblages collected for the reconstruction of acidity and salinity, the reduction in prediction error was zero, 19% and 32%.
TL;DR: In this paper, finite mixtures and two new infinite mixture models were proposed to estimate various features of interest such as the minimum age, the other component ages and the age dispersion.
TL;DR: In this article, the authors evaluate and improve on the most important design decisions made by Hinton and Shallice, relating to the task, the network architecture, the trai...
Abstract: Deep dyslexia is an acquired reading disorder marked by the Occurrence of semantic errors (e.g. reading RIVER as “ocean”). In addition, patients exhibit a number of other symptoms, including visual and morphological effects in their errors, a part-of-speech effect, and an advantage for concrete over abstract words. Deep dyslexia poses a distinct challenge for cognitive neuropsychology because there is little understanding of why such a variety of symptoms should co-occur in virtually all known patients. Hinton and Shallice (1991) replicated the co-occurrence of visual and semantic errors by lesioning a recurrent connectionist network trained to map from orthography to semantics. Although the success of their simulations is encouraging. there is little understanding of what underlying principles are responsible for them. In this paper we evaluate and, where possible, improve on the most important design decisions made by Hinton and Shallice, relating to the task, the network architecture, the trai...
TL;DR: Three hypotheses are examined that may account for the presence of multiple ornaments in males of many animals, including the multiple message hypothesis, the redundant signal hypothesis, and the unreliable signal hypothesis.
Abstract: Males of many animals have more than a single exaggerated secondary sexual character, but inter-specific variability in the number of ornaments has never been explained. We examine three hypotheses that may account for the presence of multiple ornaments. First, the multiple message hypothesis proposes that each display reflects a single property of the overall quality of an animal. This is likely to be the case for ornaments that respond to condition on different time scales. Second, the redundant signal hypothesis suggests that each ornament gives a partial indication of condition. Females pay attention to several sex traits because in combination they provide a better estimate of general condition than does any single ornament. The redundant signal hypothesis predicts that (i) multiple ornaments should be particularly common among taxa with relatively uncostly and fine-tuned female choice, and (ii) females pay equal attention to the expression of all the secondary sex traits in order to obtain an estimate of overall male condition. Finally, the unreliable signal hypothesis argues that some ornaments are unreliable indicators of overall condition and are only maintained because they are relatively uncostly to produce and there is a weak female preference for them. This predicts that (i) multiple sexual ornaments should be particularly common in taxa with the most intense sexual selection (i.e. lekking and other polygynous taxa), and (ii) there should be more evidence for condition dependence in ornaments of species with single as opposed to multiple ornaments. Both the latter predictions are supported by data on feather ornaments in birds.
TL;DR: The response of low-grade B-cell gastric MALT lymphomas to stimulating strains of H pylori is dependent on H-pylori-specific T cells and their products, rather than the bacteria themselves.
TL;DR: It is reported that human mutant cell lines that lack mitochondrial DNA, and therefore do not have a functional respiratory chain, can still be induced to die by apoptosis, and that they can be protected from apoptosis by the overexpression of bcl-2, suggesting that neither apoptosis nor the protective effect of bCl-2 depends on mitochondrial respiration.
Abstract: WHEN the mammalian proto-oncogene bcl-2 is overexpressed it can protect various types of cells both from normal and from experimentally induced apoptosis1–6 A but the molecular mechanisms involved are unknown. Although the Bcl-2 protein is membrane-associated7–10, its subcellular location is controversial: two studies have suggested that it is mainly associated with the nuclear envelope and endoplasmic reticulum8,10, whereas another study has suggested that it is mainly located in the inner mitochondrial membrane9. The latter study has suggested that Bcl-2 might protect cells from apoptosis by altering mitochondrial function and that mitochondria may be involved in apoptosis9,11. Here we report that human mutant cell lines that lack mitochondrial DNA (mtDNA), and therefore do not have a functional respiratory chain, can still be induced to die by apoptosis, and that they can be protected from apoptosis by the overexpression of bcl-2, suggesting that neither apoptosis nor the protective effect of bcl-2 depends on mitochondrial respiration. We also show that the Bcl-2 protein in overexpressing cells is associated with the nuclear envelope and endoplasmic reticulum, as well as with mitochondria.
TL;DR: It is shown that three classes of trophic factors promote oligodendrocyte survival in vitro: insulin and insulin-like growth factors, neurotrophins, particularly neurotrophin-3 (NT-3), and ciliary-neurotrophic factor (CNTF), leukemia inhibitory factor (LIF) and interleukin 6 (IL-6).
Abstract: We showed previously that oligodendrocytes and their precursors require continuous signalling by protein trophic factors to avoid programmed cell death in culture. Here we show that three classes of such trophic factors promote oligodendrocyte survival in vitro: (1) insulin and insulin-like growth factors (IGFs), (2) neurotrophins, particularly neurotrophin-3 (NT-3), and (3) ciliary-neurotrophic factor (CNTF), leukemia inhibitory factor (LIF) and interleukin 6 (IL-6). A single factor, or combinations of factors within the same class, promote only short-term survival of oligodendrocytes and their precursors, while combinations of factors from different classes promote survival additively. Long-term survival of oligodendrocytes in vitro requires at least one factor from each class, suggesting that multiple signals may be required for long-term oligodendrocyte survival in vivo. We also show that CNTF promotes oligodendrocyte survival in vivo, that platelet-derived growth factor (PDGF) can promote the survival of oligodendrocyte precursors in vitro by acting on a novel, very high affinity PDGF receptor, and that, in addition to its effect on survival, NT-3 is a potent mitogen for oligodendrocyte precursor cells.
TL;DR: The results are the first to show that it may be possible to precondition and protect the human myocardium with short controlled periods of intermittent ischaemia and reperfusion.
TL;DR: Diabetes mellitus is associated with oxidative reactions, particularly those which are catalyzed by decompartmentalized transition metals, but their causative significance in diabetic tissue damage remains to be established.
Abstract: Diabetes mellitus is a syndrome initially characterized by a loss of glucose homeostasis. The disease is progressive and is associated with high risk of atherosclerosis, kidney and nerve damage as well as blindness. Abnormalities in the regulation of peroxide and transition metal metabolism are postulated to result in establishment of the disease as well as its longer term complications. Diabetes mellitus is associated with oxidative reactions, particularly those which are catalyzed by decompartmentalized transition metals, but their causative significance in diabetic tissue damage remains to be established.
TL;DR: A finite element method for deriving photon density inside an object, and photon flux at its boundary, assuming that the photon transport model is the diffusion approximation to the radiative transfer equation, is introduced herein.
Abstract: The use of optical radiation in medical physics is important in several fields for both treatment and diagnosis. In all cases an analytic and computable model of the propagation of radiation in tissue is essential for a meaningful interpretation of the procedures. A finite element method (FEM) for deriving photon density inside an object, and photon flux at its boundary, assuming that the photon transport model is the diffusion approximation to the radiative transfer equation, is introduced herein. Results from the model for a particular case are given: the calculation of the boundary flux as a function of time resulting from a delta-function input to a two-dimensional circle (equivalent to a line source in an infinite cylinder) with homogeneous scattering and absorption properties. This models the temporal point spread function of interest in near infrared spectroscopy and imaging. The convergence of the FEM results are demonstrated, as the resolution of the mesh is increased, to the analytical expression for the Green's function for this system. The diffusion approximation is very commonly adopted as appropriate for cases which are scattering dominated, i.e., where mu(s) much greater than mu(a), and results from other workers have compared it to alternative models. In this article a high degree of agreement with a Monte Carlo method is demonstrated. The principle advantage of the FE method is its speed. It is in all ways as flexible as Monte Carlo methods and in addition can produce photon density everywhere, as well as flux on the boundary. One disadvantage is that there is no means of deriving individual photon histories.
TL;DR: The data suggest a simple mechanism whereby FGF-4 links growth and pattern formation during limb development, and suggests that polarizing activity plays a role in patterning along the proximodistal axis, in addition to its well-established role in anteroposterior patterning.
TL;DR: A neurophysiological approach to tinnitus is presented and it provides a basis for treating patients with hyperacusis, which is considering to be a pre-tinnitus state.
Abstract: This paper presents a neurophysiological approach to tinnitus and discusses its clinical implications. A hypothesis of discordant damage of inner and outer hair cells systems in tinnitus generation...
Journal Article•
TL;DR: An overview of transcription factors, their mechanism of action, their regulation and the manner in which alterations in them can result in disease can be found in a special issue of the International Journal of Biochemistry and Cell Biology as discussed by the authors.
Abstract: This special issue of the International Journal of Biochemistry and Cell Biology contains a series of review articles and original papers dealing with the topic of transcription factors The purpose of this introductory article is to provide an overview of these factors, their mechanism of action, their regulation and the manner in which alterations in them can result in disease
TL;DR: The NADPH oxidase is an electron transport chain found in lymphocytes and in the wall of the endocytic vacuole of 'professional' phagocytic cells and provides a key to the understanding of the way in which these GTP-binding proteins function.