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C U Smith

Publications and source records attributed to C U Smith.

At least 19 recordsLinked to original sources

Renatus renatus: the Cartesian tradition in British neuroscience and the neurophilosophy of John Carew Eccles.

J. C. Eccles (1903-1997) had a highly distinguished career in neurophysiology, being awarded the Nobel Prize for Medicine or Physiology in 1963. This paper sets him within the Cartesian tradition of British neurophysiology initiated by Thomas Henry Huxley in the mid-19th century. It shows how the mind-brain problematique of the Cartesian tradition troubled him throughout his career, leading him finally to a solution in terms of quantum microphysics and microphysiology. This position, which has subsequently become fashionable, is discussed and shown (at least in the form Eccles espoused) to provide no solution to the problem posed by Descartes in the early 17th century.

Brain↗

Crossing boundaries: making connectiions.

This Presidential address to the International Society for the History of the Neurosciences was given at Lausanne in September 1999. It reviews some of the contributions given at that conference and provides a brief overview of the history of the mind-brain problem in Western neuroscientific thought.

Brain↗

Coleridge's "theory of life".

Coleridge has been seen by some not so much as a poet spoiled by philosophy, but as a philosopher who was also a poet. It could be argued that his major endeavor was an attempt to save the life sciences form the mechanistic interpretation which he saw as the outcome of Lockean "mechanico-corpuscularian" philosophy. This contribution describes that endeavour. It shows its connection to the social circumstances of the time. It discusses its relationship to the poetic sensibility of the "Lake poets" and to the German thought which Coleridge absorbed during and after his sojourn in Gottingen in 1798-99. It describes the nature of his "Theory of Life" as seen not only from the posthumous publication itself, but also from the numerous hints and struggles recorded in his voluminous notebooks, letters and lecture notes. It is concluded that, although never adequately assembled, it forms the only serious attempt to construct a profound alternative to the ultimately mechanistic biology of Charles Darwin and the psysiologists of the second half of the century. As such it strongly influenced the young Richard Owen and, as is well known, was eventually overwhelmed by the Darwin-Huxley synthesis of the 1860s. Nevertheless, insofar as Coleridge's concept of life ultimately derived from his ambition to find a way of healing the Cartesian divide, we may wonder whether the recent upsurge in consciousness studies may cause us to look again at his panentheistic ideas and, discarding the obsolete and fanciful metaphysics, recast them into a more acceptable form.

Biology↗

350th anniversary of Les Passions de I'Ame.

1999 marks the three hundred and fifieth anniversary of the publication of Descrates' final work: Les Passions de l'Ame. This short paper commemorates that event and discusses the circumstances contributing to its origin and the questions which it still raises for neuropsychology three hundred and fifty years later.

Behavior↗

Thomas Henry Huxley and neuroscience.

In the latter decades of the nineteenth century Thomas Henry Huxley was at the heart of British Science: President of the British Association for the Advancement of Science (1870), President of the Royal Society (1883-86), Chairman of innumerable committees. His thought in many ways characterises the spirit of the 'high' Victorian age in Britain. He was not only the most eminent academic biologist of his time but also deeply interested in philosophical issues. His re-examination of the evolution of the brain in response to Richard Owen's 'telenomic' views formed the kernel of the notorious debate at the 1860 meeting of the British Association in Oxford. From his early youth until old age he thought long and hard about the mind/body problem. This paper follows the development of his ideas and shows how in debate with many of the leading thinkers of his age, in the X-club and the Metaphysical Society, he struggled to develop a biologically-based account of the relationship between mind and brain. However, at the end, he seems to have recognized that his position was not entirely satisfactory and ultimately famously confessing himself 'agnostic' turned from metaphysics to devote himself to more practical issues. The unresolved problems of mind and brain which perplexed Huxley remain to torment his epigoni.

History, 19th Century↗

Descartes' pineal neuropsychology.

The year 1996 marked the quattrocentenary of Descartes' birth. This paper reviews his pineal neuropsychology. It demonstrates that Descartes understood the true anatomical position of the pineal. His intraventricular pineal (or glande H) was a theoretical construct which allowed him to describe the operations of his man-like "earthen machine." In the Treatise of Man he shows how all the behaviors of such machines could then be accounted for without the presence of self-consciousness. Infrahuman animals are "conscious automata." In Passions of the Soul he adds, but only for humans, self-consciousness to the machine. In a modern formulation, only humans not only know but know that they know.

Famous Persons↗

Descartes' visit to the town library, or how Augustinian is Descartes' neurophysiology?

Rene Descartes was early accused of taking his central philosophical proposition from St Augustine. Did he also take his central neurophysiological concept from the same source? This is the question which this paper sets out to answer. It is concluded that the foundational neurophysiology propounded in L'Homme does indeed show strong and interesting resemblences to Augustine's largely Erasistratean version. Descartes, however, working within the new paradigm of seventeenth-century physical science, introduced a new principle: whereas Augustine's neurophysiology is pervaded throughout by a vital factor, the pneuma, Descartes' theory involved only inanimate material forces. It is concluded, further, that in spite of the interesting similarities between Augustinian and Cartesian neurophysiology there is no evidence for any direct plagiarism. It seems more likely that Augustine's influence was filtered through the Galenical physiologists of Descartes' own time and of the preceding century.

Europe↗

Factors determining the size frequency distribution of beta-amyloid (A beta) deposits in Alzheimer's disease.

The size frequency distributions of discrete beta-amyloid (A beta) deposits were studied in single sections of the temporal lobe from patients with Alzheimer's disease. The size distributions were unimodal and positively skewed. In 18/25 (72%) tissues examined, a log normal distribution was a good fit to the data. This suggests that the abundances of deposit sizes are distributed randomly on a log scale about a mean value. Three hypotheses were proposed to account for the data: (1) sectioning in a single plane, (2) growth and disappearance of A beta deposits, and (3) the origin of A beta deposits from clusters of neuronal cell bodies. Size distributions obtained by serial reconstruction through the tissue were similar to those observed in single sections, which would not support the first hypothesis. The log normal distribution of A beta deposit size suggests a model in which the rate of growth of a deposit is proportional to its volume. However, mean deposit size and the ratio of large to small deposits were not positively correlated with patient age or disease duration. The frequency distribution of A beta deposits which were closely associated with 0, 1, 2, 3, or more neuronal cell bodies deviated significantly from a log normal distribution, which would not support the neuronal origin hypothesis. On the basis of the present data, growth and resolution of A beta deposits would appear to be the most likely explanation for the log normal size distributions.

Aged↗

A comparison of beta-amyloid deposition in the medial temporal lobe in sporadic Alzheimer's disease, Down's syndrome and normal elderly brains.

The density of beta-amyloid (A beta) deposits was studied in the medial temporal lobe in non-demented individuals and in sporadic Alzheimer's disease (SAD) and Down's syndrome (DS). No A beta deposits were recorded in six of the non-demented cases, while in a further eight cases, these were confined to either the lateral occipitotemporal or parahippocampal gyrus. The mean density of A beta deposits in the cortex was greater in SAD and DS than in non-demented cases but with overlap between patient groups. The mean density of A beta deposits was greater in DS than SAD consistent with a gene dosage effect. The ratio of primitive to diffuse A beta deposits was greater in DS and in non-demented cases than in SAD and the ratio of classic to diffuse deposits was lowest in DS. In all groups, A beta deposits occurred in clusters which were often regularly distributed. In the cortex, the dimension of the A beta clusters was greater in SAD than in the non-demented cases and DS. The data suggest that the development of A beta pathology in the hippocampus could be a factor in the development of DS and SAD. Furthermore, the high density of A beta deposits, and in particular the high proportion of primitive type deposits, may be important in DS while the development of large clusters of A beta deposits may be a factor in SAD.

Adult↗

Sherrington's legacy: evolution of the synapse concept, 1890s-1990s.

The history of the synapse concept is traced from its inception in the 1890s to the present day. Three major periods are highlighted: the 1890s, the mid-twentieth century and modern times. The dependence of progress on the development of techniques is emphasised. The significance of the external context, the metaphors and general theory within which work proceeds, is also stressed. The development of the synapse concept can be seen to depend on a complex interplay between these internal and external factors. The reticularist/neuronist controversy provides a continuing leitmotiv.

History, 19th Century↗

What determines the size frequency distribution of beta-amyloid (A beta) deposits in Alzheimer's disease patients?

The factors determining the size of individual beta-amyloid (A beta) deposits and their size frequency distribution in tissue from Alzheimer's disease (AD) patients have not been established. In 23/25 cortical tissues from 10 AD patients, the frequency of A beta deposits declined exponentially with increasing size. In a random sample of 400 A beta deposits, 88% were closely associated with one or more neuronal cell bodies. The frequency distribution of A beta deposits which were associated with 0,1,2,...,n neuronal cell bodies deviated significantly from a Poisson distribution, suggesting a degree of clustering of the neuronal cell bodies. In addition, the frequency of A beta deposits declined exponentially as the number of associated neuronal cell bodies increased. A beta deposit area was positively correlated with the frequency of associated neuronal cell bodies, the degree of correlation being greater for pyramidal cells than smaller neurons. These data suggested: (1) the number of closely adjacent neuronal cell bodies which simultaneously secrete A beta was an important factor determining the size of an A beta deposit and (2) the exponential decline in larger A beta deposits reflects the low probability that larger numbers of adjacent neurons will secrete A beta simultaneously to form a deposit.

Aged↗

Beta-amyloid (beta/A4) deposition in the medial temporal lobe in Down's syndrome: effects of brain region and patient age.

The density of diffuse, primitive, classic and compact beta-amyloid (beta/A4) deposits was studied in the medial temporal lobe in 12 cases of Down's syndrome (DS) from 38 to 67 years of age. Total beta/A4 deposit density was greater in the adjacent cortex compared with regions of the hippocampus, and these differences were similar within each age group of patients. The ratio of the primitive to diffuse deposits was greater in the hippocampus than in the adjacent cortex. Total beta/A4 density did not vary significantly with patient age. However, the density of the diffuse deposits exhibited a parabolic, and the primitive, classic and compact deposits an inverted parabolic, response with age. Hence, in DS, (1) beta/A4 density remains relatively constant with age, (2) differences in beta/A4 density between the hippocampus and adjacent cortex are established at an early age, and (3) mature beta/A4 subtype formation depends on brain region and patient age.

Adult↗

Visualization of the thyrotropin receptor on the cell surface by potent autoantibodies.

In autoimmune thyroid disease there are various autoantibodies (Ab) to thyroid cell components. Among the best characterized are those to thyroid peroxidase (TPOAb) and to the thyrotropin receptor (TRAb). While TPOAb were successfully used to visualize TPO in human thyroid cells (HTC) and a rat thyroid cell line (FRTL5) by indirect immunofluorescence (IFL), similar attempts with TRAb and thyrotropin receptor (TSHR) failed. This could have been due to either relatively low serum levels of TRAb and/or low number of TSHR on thyroid cells. To test these hypotheses, we estimated the number of TSH binding sites on HTC, FRTL5 and Chinese hamster ovary (CHO) cells, transfected with cloned human TSHR (JP-26 cells), and for IFL staining employed 3 sera with the highest potency TRAb in our possession. A clear granular surface staining was detected on all 3 cell types with two sera; with the third, the least potent, no staining was seen. The density of staining paralleled the estimated number of TSHR per cell, i.e., JP-26 > FRTL5 > HTC. TSHR was also visualized on transiently transfected cells (COS-7-TSHR), facilitating quantitation of transfection. Our results suggest that the limiting factor in direct visualization of the TSHR is the TRAb concentration.

Animals↗

The spatial patterns of beta/A4 deposit subtypes in Alzheimer's disease.

The spatial patterns of diffuse, primitive, classic (cored) and compact (burnt-out) subtypes of beta/A4 deposits were studied in coronal sections of the frontal lobe and hippocampus, including the adjacent gyri, in nine cases of Alzheimer's disease (AD). If the more mature deposits were derived from the diffuse deposits then there should be a close association between their spatial patterns in a brain region. In the majority of tissues examined, all deposit subtypes occurred in clusters which varied in dimension from 200 to 6400 microns. In many tissues, the clusters appeared to be regularly spaced parallel to the pia or alveus. The mean dimension of the primitive deposit clusters was greater than those of the diffuse, classic and compact types. In about 60% of cortical tissues examined, the clusters of primitive and diffuse deposits were not in phase, i.e. they alternated along the cortical strip. Clusters of classic deposits appeared to be distributed independently of the diffuse deposit clusters. Cluster size of the primitive deposits was positively correlated with the density of the primitive deposits in a tissue but no such relationship could be detected for the diffuse deposits. This study suggested that there was a complex relationship between the clusters of the different subtypes of beta/A4 deposits. If the diffuse deposits do give rise to the primitive and classic varieties then factors unrelated to the initial deposition of beta/A4 in the form of diffuse plaques were important in the formation of the mature deposits.

Aged↗