Showing papers by "University College London published in 1971"
TL;DR: Preliminary observations on the behaviour of hippocampusal units in the freely moving rat provide support for this theory of hippocampal function.
5,549 citations
TL;DR: Recordings of the change in tension in striated muscle after a sudden alteration of the length have made it possible to suggest how the force between the thick and thin muscle filaments may be generated.
Abstract: Recordings of the change in tension in striated muscle after a sudden alteration of the length have made it possible to suggest how the force between the thick and thin muscle filaments may be generated.
2,050 citations
TL;DR: This chapter provides an overview of the principal features of perikaryal responses to axon injury and changes in axotomized neurons are generally assessed by comparison with the corresponding contralateral neurons of the experimental animal.
Abstract: Publisher Summary This chapter provides an overview of the principal features of perikaryal responses to axon injury. The neuron is an unusual cell. Its axon terminals may be situated at what in cellular terms is an enormous distance from the cell body (perikaryon); the volume of the latter may be but a small fraction of the total cellular volume. Yet the neuronal processes are maintained and their substance is constantly renewed from the perikaryon. The separation of an axon from its cell body results (in vertebrates) in the degeneration of the separated portion and is followed by a series of morphological changes in the perikarya. The most conspicuous of these is the disintegration, redistribution, and apparent disappearance from the cell body of cytoplasmic basophil material. Changes in axotomized neurons are generally assessed by comparison with the corresponding contralateral neurons of the experimental animal.
1,017 citations
TL;DR: In this article, the effects of different surface roughness conditions on the turbulence structure in the boundary region were investigated and it was shown that ejection phases corresponded with ejection of low momentum fluid outwards from the boundary whilst inrush phases were associated with the transport of high momentum fluid inwards towards the boundary.
Abstract: An experimental study of boundary-layer turbulence in a free surface channel flow is described. Attention is concentrated on the effects of different surface roughness conditions on the turbulence structure in the boundary region. Hydrogen bubble flow tracers and medium high-speed motion photography were used to obtain an instantaneous visual and quantitative description of the flow field. In particular it proved possible to record instantaneous longitudinal and vertical velocity profiles from which distributions of the instantaneous Reynolds stress contribution were computed.Two well-defined intermittent features of the flow structure were visually identified close to the boundary. These consisted of fluid ejection phases, previously reported by Kline et al. (1967) for smooth boundary flow, and fluid inrush phases. Conditional averaging of the instantaneous velocity data yielded quantitative confirmation that ejection phases corresponded with ejection of low momentum fluid outwards from the boundary whilst inrush phases were associated with the transport of high momentum fluid inwards towards the boundary. Inrush and ejection events were present irrespective of the surface roughness condition.Conditional averaging also indicated that both inrush and ejection sequences correlate with an extremely high contribution to Reynolds stress and hence turbulence production close to the boundary. Indeed the present results, taken with those from previous studies, suggest that turbulence production is dominated by the joint contribution from the inrush and ejection events. It is emphasized that these structural features are intermittent, forming important linked elements of a randomly repeating cycle of wall-region turbulence production which is apparently driven by some violent three-dimensional instability mechanism.Whilst the most coherent effects of the observed inrush phases appear to be mainly confined to a region close to the boundary, the influence of the ejection phases is far more extensive. The ejected low momentum fluid elements, drawn from the viscous sublayer and from between the interstices of the roughness elements, travel outwards from the boundary into the body of the flow and give rise to very large positive contributions to Reynolds stress at points remote from the boundary. This effect is sufficiently strong to prompt the suggestion that the ejection process could represent a universal and dominant mode of momentum transport outside the immediate wall region and possibly extending across the entire thickness of the boundary layer.A structural model based on the present observations is seen to exhibit consistency with many commonly visualized features and recorded average properties of turbulent boundary-layer flows in general.
879 citations
TL;DR: Electron microscopy of vertical longitudinal sections of chick heart fibroblasts moving on an Araldite substratum shows that the cell approaches close to the substratum in localised regions which tend to form electron-dense plaques containing longitudinal filaments, suggesting that the plaques are linked up to the fibrillar system of the cell.
672 citations
569 citations
503 citations
TL;DR: In rabbits, anaesthetized with urethane/chloralose, stimulation with tungsten microelectrodes was employed to initiate a volley in the perforant path fibres which made en-passage contacts with the apical dendrites of dentate granule cells, indicating an active synaptic sink restricted to the middle third of the dendritic region.
Abstract: 1.
In rabbits, anaesthetized with urethane/chloralose, stimulation with tungsten microelectrodes was employed to initiate a volley in the perforant path fibres which made en-passage contacts with the apical dendrites of dentate granule cells. The ensuing activation pattern was studied by recording the extracellular field potentials in the dentate area and the extra and intracellular responses of single granule cells.
2.
The afferent perforant path volley appeared as a small triphasic potential followed after 0.8 msec by a monosynaptic wave, which was maximally negative in the middle third of the molecular layer, corresponding to the region of the perforant path synapses on the granule cell dendrites. The wave became abruptly positive in the inner third of the molecular layer. After removal of the CA1, reversal occurred also in the outer third of the molecular layer, indicating an active synaptic sink restricted to the middle third of the dendritic region.
3.
A perforant path volley, propagating at a speed of about 3.3 m/sec, discharged granule cells lying in a horseshoeshaped segment of the dentate area. The dentate area is thus divided into a series of segments or lamellae by the perforant path input. Laterally, the perforant path fibres run through a bottle neck, deep to the angular bundle, before fanning out to enter the various segments of the dentate area of the dorsal hippocampus.
4.
A stimulus applied to the lateral region of the angular bundle activated the perforant path directly as well as indirectly. The indirect activation was presumably mediated by commissural fibres to the entorhinal area from which the perforant path originates.
5.
The negativity recorded extracellularly in the synaptic layer had the same onset as, but was phase advanced with respect to the intracellularly recorded EPSP. The monosynaptic extracellular negative wave was therefore interpreted as reflecting the synaptic current generating the intracellular EPSP and is termed the extracellular EPSP.
6.
When the perforant path volley was sufficiently large, a compound spike became superimposed on the extracellular EPSP. The spike was maximally negative in the granule cell body layer and positive in the outer dendritic region. Occasionally, multiple single cell discharges could be recorded in the granular layer. These unitary discharges always coincided in time with the compound spike and their number parallelled the size of the compound spike. The latter, therefore, reflects the number of nearly synchronously discharged cells and is termed the granule cell population spike.
7.
Typically, the granule cells discharged only once in response to a single perforant path volley. Subsequent discharges were blocked by inhibitory postsynaptic potentials, IPSPs. The postsynaptic excitatory response time varied between 5 msec and 1.4 msec depending on the size of the perforant path volley. A value of about 2 msec was most commonly observed in response to moderate or strong stimuli.
8.
The granule cells were discharged by a perforant path volley of increasing size only after a considerable growth of the extracellular EPSP had taken place. Apparently, the discharge requires summation of a large number of relatively small individual EPSPs. This may be a mode of synaptic activation characteristic of pathways with numerous boutons en-passage making contact with spines of profusely branching dendrites.
484 citations
01 Jan 1971
TL;DR: The concept of a barrier between blood and brain and the brain and spinal cord derives from the classical studies of Ehrlich and of Goldmann on vital staining but in the thirties and forties some doubt was cast on this concept.
Abstract: The concept of a barrier between blood, on the one hand, and the brain on the other derives from the classical studies of Ehrlich and of Goldmann on vital staining; it was noted that a large variety of acid dyes, of which trypan blue was one, would pass out of the blood into the tissues of the body making them voloured; the brain and spinal cord stood out in contrast to the rest of the tissues in that, with the exception of highly localized regions, such as the area postrema, they remained unstained. In the thirties and forties of this century some doubt was cast on this concept of a barrier between blood and brain; thus King in 1938 (1) argued that the essential phenomenon was one of failure to stain, and this could have been due to the absence of suitable connective tissue to take up the stain.
454 citations
TL;DR: In this paper, the initial value problem for linearized perturbations is discussed, and the asymptotic solution for large time is given for values of the Reynolds number slightly greater than the critical value, above which perturbation may grow.
Abstract: The initial-value problem for linearized perturbations is discussed, and the asymptotic solution for large time is given. For values of the Reynolds number slightly greater than the critical value, above which perturbations may grow, the asymptotic solution is used as a guide in the choice of appropriate length and time scales for slow variations in the amplitude A of a non-linear two-dimensional perturbation wave. It is found that suitable time and space variables are et and e½(x+a1rt), where t is the time, x the distance in the direction of flow, e the growth rate of linearized theory and (−a1r) the group velocity. By the method of multiple scales, A is found to satisfy a non-linear parabolic differential equation, a generalization of the time-dependent equation of earlier work. Initial conditions are given by the asymptotic solution of linearized theory.
440 citations
TL;DR: In this paper, the effects of prior experience on a deceptive reasoning problem was investigated and the results showed that prior experience was ineffective in allowing subsequent insight to be gained into the problem.
Abstract: This study is concerned with the effects of prior experience on a deceptive reasoning problem. In the first experiment the subjects (students) were presented with the problem after they had experienced its logical structure. This experience was, on the whole, ineffective in allowing subsequent insight to be gained into the problem. In the second experiment the problem was presented in “thematic” form to one group, and in abstract form to the other group. Ten out of 16 subjects solved it in the thematic group, as opposed to 2 out of 16 in the abstract group. Three hypotheses are proposed to account for this result.
TL;DR: There are calculated to be approximately 109 acetylcholine receptors in a frog muscle fibre, which has important implications for theories concerning the nerve to muscle transmission mechanism.
Abstract: There are calculated to be approximately 109 acetylcholine receptors in a frog muscle fibre. This has important implications for theories concerning the nerve to muscle transmission mechanism.
TL;DR: Nitrazepam had significantly less oculomotor effect but significantly more subjective effects than phenobarbitone, related to theevidence that smooth tracking suppression arises from drug action on brain stem systems, and the evidence that benzodiazepines affect brain stem Systems less than the limbic system.
TL;DR: It is reported that α-bungarotoxin similarly blocks the cholinergically innervated electric tissue of Torpedo marmorata, and described isolation of the single membrane protein to which the toxin is bound.
Abstract: LEE and his co-workers have reported1–3, and we have confirmed, that α-bungarotoxin (α-BuTX), a component of the venom of a Formosan snake (Bungarus multicinctus), blocks specifically and irreversibly the depolarizing action of acetylcholine at vertebrate neuromuscular junctions. We wish to report that this toxin similarly blocks the cholinergically innervated electric tissue of Torpedo marmorata, and to describe isolation of the single membrane protein to which the toxin is bound.
TL;DR: Mapping of the receptive fields of cells in the thalamus and cortex after section of the dorsal columns in the rat reveals evidence of functional reorganization in the central nervous system.
Abstract: Mapping of the receptive fields of cells in the thalamus and cortex after section of the dorsal columns in the rat reveals evidence of functional reorganization in the central nervous system.
TL;DR: Human alcohol dehydrogenase has been investigated by spectrophotometry assay and by starch‐gel electrophoresis and it is shown that the former is superior to the latter in terms of specificity and purity.
Abstract: Ann. H u m . Genet., Lond. (1971), 34, 251 Printed in Great Britain Developmental changes and polymorphism in human alcohol dehydrogenase BY MOYRA SMITH, D. A. HOPKINSON AND HARRY HARRIS M.R.C. Human Biochemical Genetics Unit, Galton Laboratory, University College London I n man, alcohol dehydrogenase (alcohol: NAD oxidoreductase E.C. 1 . 1 . 1 . 1 ) occurs princi- pally in liver, though low levels of activity have aIso been found in lung, kidney and the gastro- intestinal tract (Moser, Papenberg & von Wartburg, 1968). Evidence for at least three distinct isozymes has been obtained by chromatography of liver extracts on CM cellulose (Blair & Vallee, 1966) and also by electrophoresis (Moser et al. 1968; Pikkarainen & Raiha, 1969; Murray & Motulsky, 1970). Von Wartburg, Papenberg & Aebi (1965) reported that certain individuals have an atypical form of alcohol dehydrogenase associated with an increased level of activity. The usual and atypical forms of the enzyme were shown to differ markedly in pH activity curves with ethanol as substrate. The pH optimum for the usual form was found to be pH 10.8 and for the atypical form pH 8.5. The enzymes also differed in the relative rates at which they oxidized various other alcohols, and in the degree of inhibition produced by various metal binding agents. On the other hand no significant differences were observed in Michaelis constants for the substrates ethanol or acetaldehyde or for the corresponding coenzymes NAD or NADH. Also the pH activity curve with acetaldehyde as substrate was essentially the same for both enzymes, having an optimum at pH 6.0-6.5. A simple screening test to distinguish the usual from the atypical enzyme in crude liver homo- genates was designed (von Wartburg et al. 1965). This involves determining the ratio of the activity at pH 11.0 to that at pH 8-8 with ethanol as substrate under standard conditions. The usual enzyme gives a value for this ratio greater than 1.0, and the atypical enzyme less than 1.0. In a survey of 59 liver samples from different individuals in Switzerland, 12 were found to have the atypical alcohol dehydrogenase, and in another series of 50 individuals from London, 2 were found to be atypical (von Wartburg & Schiirch, 1968). The atypical enzyme occurred in indi- viduals varying from 16 to 82 years of age. Pikkarainen & Raiha (1967) reported that alcohol dehydrogenase activity in liver is low during foetal life and reaches adult levels about 5 years after birth. Changes in electrophoretic pattern have also been noted during development (Pikkarainen & Raiha, 1969; Murray & Motulsky, 1970). In the earliest stages only a single isozyme is observed but later further iso- zymes appear. I n adult liver individual variations in the relative contribution of the different isozymes to the total activity have been noted (von Wartburg & Schiirch, 1968), but no clear electrophoretic differences between the usual and atypical alcohol dehydrogenases as determined by the ratio of activity at pH 11.0 and pH 8.8 were detected. The present paper is concerned with a study of human alcohol dehydrogenase in which liver, lung, kidney and intestinal material from foetuses, infants and adults has been examined. The en- zyme has been investigated both by spectrophotometric assay at different pH’s and by starch-gel
TL;DR: In this paper, a method for the calculation of optimum cooling curves based on a simple mathematical description of the individual kinetic processes involved in a crystallization operation is presented, and the results show that the programmed cooling brings about a significant increase in the size and an improvement in the quality of crystals from a batch crystallizer.
TL;DR: The source of reducing equivalents for gluconeogenesis is examined and it is concluded that transfer of carbon occurs both as malate and aspartate, and that the requirement for reducing equivalents is met in part by the transfer of malate to the cytosol and by NADH generated by the fumarate cycle geared to urea production.
TL;DR: Electrophysiological and electron-microscopic studies were made of the effect of lanthanum ions on frog neuromuscular junctions, finding that with continued La-treatment, the frequency of miniature end-plate potentials subsides slowly until they are no longer detectable at most end-plates.
Abstract: 1. Electrophysiological and electron-microscopic studies were made of the effect of lanthanum ions on frog neuromuscular junctions. 2. In the presence of 1 mM La$^{2+}$, nerve impulses continued to invade the nerve terminals but ceased to release transmitter. 3. Lanthanum caused a rapid and large increase in the frequency of miniature end-plate potentials; presumably because La activates the mechanism of transmitter release without the usual prerequisite of presynaptic membrane depolarization. At 4 degrees C, La caused a 10 000-fold, or even larger increase in the rate of leakage of transmitter quanta. Such high rate of transmitter release was not accompanied by obvious changes in electron-microscopic structure of the nerve terminals. 4. With continued La-treatment, the frequency of miniature end-plate potentials subsides slowly until they are no longer detectable at most end-plates. During this period the number of synaptic vesicles is reduced until practically all the endings become completely depleted of synaptic vesicles. In contrast, coated vesicles and membrane-bound tubes and cysternae become more numerous.
TL;DR: Although the striate cortex sends a convergent input to the cortex of the posterior bank of the superior temporal sulcus, it also sends a topographically organised input to areas 18 and 191,16, which raises the possibility that there might be two independent pathways between the Striate cortex with its precise topographical organisation and the cortex that has been shown to receive afferents from large parts of the primary visual cortex.
TL;DR: In this article, the authors considered the problem of determining the possible f-vectors of simplicial polytopes and proved a conjecture about the form of the sclution to this problem.
Abstract: In this paper is considered the problem of determining the possiblef-vectors of simplicial polytopes. A conjecture is made about the form of the sclution to this problem; it is proved in the case ofd-polytopes with at mostd+3 vertices.
TL;DR: Potentiation of EPSPs may be an important mechanism behind the frequency potentiation of mass responses characteristic of the hippocampal formation, compared with that observed in other types of synapses.
Abstract: 1.
In rabbits, initially anaesthetized by urethane/chloralose and maintained on urethane alone, the perforant path, contacting the apical dendrites of the dentate granule cells by way of boutons en-passage, was activated by paired stimuli. The effect of the first conditioning stimulus was studied by recording the extracellular field response and the extra- and intracellular responses of single granule cells to a second test stimulus.
2.
The monosynaptic test EPSP recorded extra- as well as intracellularly was potentiated by a preceding volley in the perforant path. The rate of rise and the amplitude of the extracellular test EPSP increased by as much as 100% at an optimal conditioning-test interval of about 25 msec. The total duration of the potentiation was 200–300 msec. Sometimes the potentiation was followed by a slight subnormal phase.
3.
The EPSP potentiation was not due to a larger presynaptic test volley since (1) the size of the presynaptic fibre potential was not effected, and (2) removal of the entorhinal area did not reduce the effect.
4.
The potentiation was not due to the recurrent inhibitory hyperpolarization of the postsynaptic membrane because (1) weak conditioning volleys potentiated the EPSPs without discharging the granule cells or producing any inhibition. (2) Conditioning antidromic volleys produced marked inhibition and IPSPs but had no effect on the test perforant path EPSP.
5.
Different mechanisms that may be responsible for the EPSP potentiation are discussed. The potentiation is compared with that observed in other types of synapses. Potentiation of EPSPs may be an important mechanism behind the frequency potentiation of mass responses characteristic of the hippocampal formation.
TL;DR: Glycyl-D-phenylalanine was immobilised in the same way and used for purification of carboxypeptidase A (peptidyl-L-amino-acid hydrolase, EC 3.4.1.2) by affinity chromatography.
TL;DR: In this paper, a method for the measurement of permittivity at microwave frequencies using an open resonator is proposed, and an experimental procedure is developed, and a thorough experimental study of the method has shown that experimental errors can be made very small indeed.
Abstract: A method for the measurement of permittivity at microwave frequencies using an open resonator is proposed. The theory of the method is developed, and an experimental procedure is evolved and justified. It is shown that the present method has advantages over other open resonator methods which have been proposed, and a thorough experimental study of the method has shown that experimental errors can be made very small indeed. Since the very beginnings of modern microwave techniques in the 1940s, many alternative methods of measuring the complex permittivity of gases, liquids and solids have been devised. Most of these have employed a cavity resonator or a length of waveguide as a means of defining the configuration of the electromagnetic field with the precision needed for accurate quantitative analysis of the experimental results. Although very satisfactory results have been obtained using such methods, they become increasingly difficult to apply as the wavelength decreases. For the solid dielectric materials with which the present paper is exclusively concerned, a major problem is the accurate machining of a specimen of the material to fit closely into the resonator or waveguide. Even very small air gaps between the dielectric material and the metal wall can cause large errors, and this problem is obviously more serious at shorter wavelengths since the fractional error corresponding to a given absolute error in the dimensions of the specimen is inversely proportional to the wavelength. Another difficulty is encountered at very high frequencies in the resonant cavity method of measurement of the loss tangent of a dielectric material when this has a small value. The accuracy of measurement begins to decrease when the loss tangent falls below the reciprocal of the Q factor of the empty resonant cavity. Since this Q factor varies as fo , where f0 is the resonant frequency it is clear that the method is unsatisfactory for low-loss materials at high frequencies. The pioneer work of Culshaw & Anderson (I962) on the measurement of permittivity and dielectric loss with a millimetre wave Fabry-Perot interferometer was the first successful attempt to use an open resonator for this purpose. However, the use of parallel-plane mirrors rather than spherical mirrors gives rise to a field distribution within the resonator which is not readily amenable to mathematical analysis. Moreover, the diffraction losses are much larger than is the case when spherical mirrors are used in a suitable configuration.
TL;DR: In this paper, the hydrodynamic force on a small particle of a dilute suspension when in a slow streaming motion past a large spherical or cylindrical obstacle is estimated for the situation when the particle is moving close to the obstacle.
TL;DR: With the appropriate techniques the retinal receptor (first order) synapse is shown to contain plain synaptic vesicle, complex (coated) vesicles and shell fragments, suggesting that in both cases the synaptic vESicles have arisen from the complex ves particles.
TL;DR: Evidence is presented that the rat-liver form B and the Micrococcus lysodeikticus RNA polymerases bind to and transcribe from different sites on the chromatin DNA.
Abstract: The transcription of rat-liver chromatin has been studied using partially purified from AI and highly purified form B DNA-dependent RNA polymerases isolated from rat liver. Chromatin contains endogenous RNA polymerase activity. This activity is evident only when the RNA polymerase assays are carried out at high ionic strength and its appearance as the ionic-strenght increases is thought to be due to the removal of chromatin-associated proteins which block further transcription by the bound enzyme. This activity is insensitive to the rifampicin derivative AF/0-13 which is shown to inhibit initiation of RNA synthesis by mammalian RNA polymerases. From AI polymerase is virtually inactive in the transcription of chromatin whereas the from B RNA polymerase (α-amanitin sensitive) actively transcibes chromatin. This activity has two salt concentration optima: (a) 0.01 M (NH4)2SO4 or 0.03 M KCI; (b) 0.16 M (NH4)2SO4 or 0.25 MKCI. Both these activities are inhibited by rifampicin AF/0-13. A comparison of the activity of the rat-liver from B polymerase and the Micrococcus lysodeikticus RNA polymerase demonstrates that chromatin is a more efficent template for the rat-liver enzyme. Evidence is presented that the rat-liver form B and the Micrococcus lysodeikticus RNA polymerases bind to and transcribe from different sites on the chromatin DNA.
TL;DR: Multiple NP isozymes were found in most human tissues and the best resolution was achieved by electrophoresis in a buffer system containing lithium ions.
Abstract: SUMMARY
1. A method, for the starch gel electrophoresis of human nucleoside phosphorylase (NP) is described. Multiple NP isozymes were found in most human tissues and the best resolution of these isozymes was achieved by electrophoresis in a buffer system containing lithium ions.
2. Tissue to tissue variation in the complexity of the NP isozyme patterns and the examination of NP isozymes in relatively young red cells, suggest that a primary isozymic form of human NP is modified in vivo with generation of several secondary isozymes. The slowest isozyme is probably the primary form in all tissues, the secondary isozymes have greater anodal electro-phoretic mobilities. Storage experiments carried out with fibroblasts indicate that in vitro modification of the NP isozyme patterns may also occur.
3. Three electrophoretically different genetically determined variants of NP were found in a survey of red cell lysates from 2178 unrelated individuals; one of them was found twice. Family studies showed that these variants occur in individuals heterozygous for a common allele (NP1) and a variant allele (either NP2, NP3 or NP*) at an autosomal locus.
4. Examination of the NP isozymes in cultured fibroblasts and hair follicle cell extracts obtained from individuals with variant red cell phenotypes suggests that NP has a trimeric structure. In vitro hybridization experiments using a freeze-thaw-NaCl technique with mouse and human liver and with calf spleen and human liver NP support this view.
5. The molecular size of human NP by gel filtration chromatography is c. 84,000.