Showing papers by "University College London published in 1983"

Evidence for a central component of post-injury pain hypersensitivity

Abstract: Noxious skin stimuli which are sufficiently intense to produce tissue injury, characteristically generate prolonged post-stimulus sensory disturbances that include continuing pain, an increased sensitivity to noxious stimuli and pain following innocuous stimuli. This could result from either a reduction in the thresholds of skin nociceptors (sensitization)1,2 or an increase in the excitability of the central nervous system so that normal inputs now evoke exaggerated responses3,4. Because sensitization of peripheral receptors occurs following injury5–7, a peripheral mechanism is widely held to be responsible for post-injury hypersensitivity. To investigate this I have now developed an animal model where changes occur in the threshold and responsiveness of the flexor reflex following peripheral injury that are analogous to the sensory changes found in man. Electrophysiological analysis of the injury-induced increase in excitability of the flexion reflex shows that it in part arises from changes in the activity of the spinal cord. The long-term consequences of noxious stimuli result, therefore, from central as well as from peripheral changes.

A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium

Abstract: We have identified a cell type in 7-day-old rat optic nerve that differentiates into a fibrous astrocyte if cultured in the presence of fetal calf serum and into an oligodendrocyte if cultured in the absence of serum. In certain culture conditions some of these cells acquire a mixed phenotype, displaying properties of both astrocytes and oligodendrocytes. These observations suggest that fibrous astrocytes and oligodendrocytes develop from a common progenitor cell and provide a striking example of developmental plasticity and environmental influence in the differentiation of CNS glial cells.

Fitting and Statistical Analysis of Single-Channel Records

Abstract: The aims of analysis of single channel records can be considered in two categories. The first is to allow one to observe results at leisure in order to determine their qualitative features. It may, for example, be found that the single-channel currents were not all of the same amplitude or that they showed obvious grouping into bursts or that artifacts appeared on the record that might be misleading. These effects are often not easy to see on the oscilloscope screen as an experiment proceeds (especially since it is common practice for the signal to be rather heavily filtered for observation during the experiment). For this aim to be fulfilled, highly automated methods of analysis are not desirable.

The contributions of position, direction, and velocity to single unit activity in the hippocampus of freely-moving rats.

Abstract: Isolated single units in rat dorsal hippocampus and fascia dentata were classified as 'Theta' or 'Complex-Spike' cells, and their firing characteristics were examined with respect to position, direction and velocity of movement during forced choice, food rewarded search behavior on a radial eight arm maze. Most spikes from CS cells occurred when the animal was located within a particular place on the maze and moving in a particular direction. Theta cells had very low spatial selectivity. Both cell categories had discharge probabilities which increased somewhat as a function of running velocity but tended to asymptote well before half-maximal velocity. The place/direction specificity of CS cells was significantly higher in CA1 than in CA3 and CA3 CS cells exhibited a striking preference for the inward radial direction. The pronounced directional selectivity of CS cells, at least in the present environment, suggests that they fire in response to complex, but specific, stimulus features in the extramaze world rather than to absolute place in a non-egocentric space. An alternative possibility is that the geometrical constraints of the maze surface have a profound influence on the shapes of the response fields of CS cells.

Quantum defect theory

Abstract: Quantum defect theory (QDT) is concerned with the properties of an electron in the field of a positive ion and, in particular, with expressing those properties in terms of analytical functions of the energy. It provides a unified theory of bound states, including series perturbations, autoionisation and electron-ion scattering, both elastic and inelastic. The main emphasis of the review is on the foundations of the theory. Properties of Coulomb functions are discussed in some detail and outline sketches are given of relevant topics in collision theory and radiative theory. One-channel and many-channel QDT are discussed separately. Applications to the following problems are considered: resonances, atomic collision calculations, systems with two energy levels of the ion core, helium, other rare gases, alkaline earths and other atomic systems, molecular hydrogen, dielectronic recombination.

The Principles of the Stochastic Interpretation of Ion-Channel Mechanisms

Abstract: Most mechanisms that are considered for ion channels (as for any other sort of chemical reaction) involve reversible transitions among the various possible discrete chemical states in which the system can exist. Other sorts of mechanisms may, of course, exist; for example, there may be an irreversible reaction step, a problem that is considered in Section 7. Our primary aim is to gain insight about the nature of the reaction mechanism from experimental observations. In this process, we may also obtain estimates of numerical values for the rate constants in the mechanism.

Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve injured rats

Abstract: Single units were recorded in dorsal roots or in the sciatic nerve of anaesthetised rats. It was shown by making sections, by stimulation and by collision that some ongoing nerve impulses were originating from the dorsal root ganglia and not from the central or peripheral ends of the axons. In a sample of 2731 intact or acutely sectioned myelinated sensory fibres, 4.75% +/- 3.7% contained impulses generated within the dorsal root ganglia. In 2555 axons sectioned in the periphery 2-109 days before, this percentage rose to 8.6% +/- 4.8%. There was a considerable variation between animals; 0-14% in intact and acutely sectioned nerves and 1-21% in chronically sectioned nerves. The conduction velocity of the active fibres did not differ significantly from the conduction velocity of unselected fibres. The common pattern of ongoing activity from the ganglion was irregular and with a low frequency (about 4 Hz) in contrast to the pattern of impulses originating in a neuroma which usually have a higher frequency with regular intervals. Slight mechanical pressure on the dorsal root ganglion increased the frequency of impulses. Unmyelinated fibres were also found to contain impulses originating in the dorsal root ganglion. In intact or acutely sectioned unmyelinated axons, the percentage of active fibres 4.4% +/- 3.5% was approximately the same as in myelinated fibres but there were no signs of an increase following chronic section. Fine filament dissection of dorsal roots and of peripheral nerves and collision experiments showed that impulses originating in dorsal root ganglia were propagated both orthodromically into the root and antidromically into the peripheral nerve. It was also shown that the same axon could contain two different alternating sites of origin of nerve impulses: one in the neuroma or sensory ending and one in the ganglion. These observations suggest that the dorsal root ganglion with its ongoing activity and mechanical sensitivity could be a source of pain producing impulses and could particularly contribute to pain in those conditions of peripheral nerve damage where pain persists after peripheral anaesthesia or where vertebral manipulation is painful.

Capsaicin and sensory neurones--a review.

Abstract: In the late fifties and sixties Jancso published a series of papers on ‘the peculiar pharmacological effect of capsaicin Capsaicin or 8-methyl-N-vanillyi-6-nonenamide is the irritant compound in the capsicum plant (red pepper, chilli pepper, etc.). After initial violent irritation, capsaicin application renders animals and man insensitive to further noxious chemical stimuli. This desensitization can last for weeks or months following systemic administration in rats [47]. Despite this powerful effect, at that time, no clear-cut morphological lesion could be found to accompany it. In 1977, however, Jancso’s son and colleagues reported on the effects of capsaicin administered to neonatal rats. This was followed by a life-long insensitivity to chemical irritants accompanied by destruction of the small ‘B-type’ dorsal root ganglion cells [41]. It was this discovery that began a great surge of interest in the effects of capsaicin, in laboratories all over the world, producing the considerable amount of information that we have about its actions today. Its potential as a specific toxin for peripheral C fibres has made it of particular interest to neurobiologists concerned with pain mechanisms. This review was written as a result of a meeting on capsaicin in November 1981 at the Medical Research Council in London. At this meeting, neuroscientists of different disciplines who had used capsaicin in their research or studied its mode of action came together to discuss problems. Questions that arise out of the work so far, include: (1) Is the action of capsaicin on the peripheral nerve restricted to C fibres? (2) Does capsaicin have a direct effect on central nervous tissue? (3) Is capsaicin an axonal transport blocker? (4) What is the effect of capsaicin on nerve membrane? (5) Does capsaicin treatment result in analgesia? The following review shows to what extent we can answer these and other important questions about capsaicin. It is important too, in a general sense, to decide how useful a tool capsaicin is in understanding the nervous system and how much we have learnt from it so far. The review will be restricted almost completely to the somatosensory system. The effects of capsaicin on cardiovascular, respiratory, thermoregulatory and gastroin-

Pain and Fatigue after Concentric and Eccentric Muscle Contractions

Abstract: 1. Normal subjects performed a step test in which the quadriceps of one leg contracted concentrically while the contralateral muscle contracted eccentrically. 2. Maximal voluntary force and the force: frequency relationship were altered bilaterally as a result of the exercise, the changes being greater in the muscle which had contracted eccentrically. Recovery occurred over 24 h. 3. Electromyographic studies using three sites on each muscle showed an increase in electrical activation during the exercise only in the muscle which was contracting eccentrically. Recovery followed a time course similar to that of the contractile properties. 4. Pain and tenderness developed only in the muscle which had contracted eccentrically. Pain was first noted approximately 8 h after exercise and was maximal at approximately 48 h after exercise, at which time force generation and electrical activation had returned to pre-exercise values. 5. Eccentric contractions cause more profound changes in some aspects of muscle function than concentric contractions. These changes cannot be explained in simple metabolic terms, and it is suggested that they are the result of mechanical trauma caused by the high tension generated in relatively few active fibres during eccentric contractions.

Reading for meaning and reading for sound in autistic and dyslexic children

Abstract: Autistic, dyslexic and normal readers matched for reading age (RA) were compared on a large range of oral reading tasks. In terms of single word reading autistic children demonstrated intact processing strategies, entirely in keeping with their RA level, while dyslexic children failed on phonological, but not on lexical or semantic processing. With connected prose, the autistic children showed failure in reading for meaning. This failure was traced to a difficulty in using semantic context in the absence of syntactic cues. Dyslexic children showed superior ability in using semantic context relative to their RA level. The reading problems in the two groups can thus be seen as complementary.

Involvement of guanine nucleotide-binding protein in the gating of Ca2+ by receptors

Abstract: The introduction of impermeant aqueous solutes into individual cells by microinjection has long been established1,2 but the difficulties of manipulating the cytosol composition of large populations of microscopic cells have only recently been overcome. Successful techniques include a dielectric breakdown procedure3–6, treatment with micromolar concentrations of ATP4− (ref. 7) and also with very small (that is non-agglutinating, non-fusogenic) amounts of Sendai virus8. So far, attention has been concentrated on the behaviour of the cells (generally their response to applied Ca2+ buffers) at the time when the membrane permeability lesions are open, and thus cytosol and external medium are in contact. I now report a novel technique for monitoring the state of molecular solute permeability in cell membranes and show that the lesions generated by ATP4− in the membrane of mast cells can be closed within seconds of adding Mg2+ so that a cycle of permeabilization and resealing can be used to explore the effect of foreign compounds trapped in the cytosol of effectively intact cells. I show that non-hydrolysable GTP analogues, introduced into the cytosol of mast cells, cause them to undergo exocytotic secretion in response to addition of extracellular Ca2+. This finding is discussed in the light of previous experience relating guanine nucleotide regulatory proteins as intermediaries between receptors and the transducers which they control.

A sufficient condition for the instability of columnar vortices

Abstract: The inviscid instability of columnar vortex flows in unbounded domains to three-dimensional perturbations is considered. The undisturbed flows may have axial and swirl velocity components with a general dependence on distance from the swirl axis. The equation governing the disturbance is found to simplify when the azimuthal wavenumber n is large. This permits us to develop the solution in an asymptotic expansion and reveals a class of unstable modes. The asymptotic results are confirmed by comparisons with numerical solutions of the full problem for a specific flow modelling the trailing vortex. It is found that the asymptotic theory predicts the most-unstable wave with reasonable accuracy for values of n as low as 3, and improves rapidly in accuracy as n increases. This study enables us to formulate a sufficient condition for the instability of columnar vortices as follows. Let the vortex have axial velocity W(r), azimuthal velocity V(r), where r is distance from the axis, let Ω be the angular velocity V/r, and let Γ be the circulation rV. Then the flow is unstable if $ V\frac{d\Omega}{dr}\left[ \frac{d\Omega}{dr}\frac{d\Gamma}{dr} + \left(\frac{dW}{dr}\right)^2\right] < 0.$

Cross-cultural differences in the perception of female body shapes

Abstract: Whereas in Western societies there is an inverse relationship between high social class and low body weight, the inverse is true of less developed, non-Western societies. It has also been shown that the longer immigrants have been in Western societies, the less obese they tend to be. This study examined how Kenyan Asian, British and Kenyan British females from similar backgrounds perceived female body shapes. As predicted, the Kenyans rated larger figures more favourably and smaller figures less favourably than the British. Also, as predicted, it was found that the Kenyan Asian British were more similar to the British group in their perceptions. The results support the view that social and cultural factors play dominant role in the perception of one's own and others' body shapes. In addition, the results reveal that in Britain preferences for small body shapes to the point of being anorexic are not uncommon.

Large delayed plasma creatine kinase changes after stepping exercise.

Abstract: Muscle changes have been examined in 16 normal subjects (eight female) after both a 20-minute and a prolonged step test. Stepping differs from most exercise tests in that it involves eccentric contractions (negative work) in which the active muscle is lengthened. Plasma creatine kinase (CK), muscle force, contractile properties, and tenderness in the quadriceps were measured for up to 9 days after the exercise. Muscle tenderness was experienced only in the muscles that had performed eccentric contractions (i.e., stepped down). All subjects showed some early rise in CK (less than 400 IU/liter) but eight (both male and female) showed a much greater response (up to 34,500 IU/liter) which took a long time to reach peak levels (4-5 days after stepping). It is suggested that eccentric contractions involved in this form of exercise result in some particular form of muscle damage which, in susceptible subjects, may initiate changes giving rise to a large delayed release of muscle enzymes.

Oscillations of intracellular Ca2+ in mammalian cardiac muscle.

Abstract: Contraction of cardiac muscle depends on a transient rise of intracellular calcium concentration ([Ca2+]i) which is initiated by the action potential1. It has, however, also been suggested that [Ca2+]i can fluctuate in the absence of changes in membrane potential. The evidence for this is indirect and comes from observations of (1) fluctuations of contractile force in intact cells2–5, (2) spontaneous cellular movements6, and (3) spontaneous contractions in cells which have been skinned to remove the surface membrane7. The fluctuations in force are particularly prominent when the cell is Ca2+-loaded, and have been attributed to a Ca2+-induced Ca2+ release from the sarcoplasmic reticulum7. In these conditions of Ca2+-loading the normal cardiac contraction is followed by an aftercontraction8 which has been attributed to the synchronization of the fluctuations5. The rise of [Ca2+]i which is thought to underlie the aftercontraction also produces a transient inward current3. This current, which probably results from a Ca2+-activated nonspecific cation conductance9, has been implicated in the genesis of various cardiac arrhythmias. However, despite the potential importance of such fluctuations of [Ca2+]i their existence has, so far, only been inferred from tension measurement. Here we present direct measurements of such oscillations of [Ca2+]i.

Parthenogenetic activation of mouse oocytes in vitro with ethanol and benzyl alcohol.

Abstract: Treatment in vitro of ovulated mouse oocytes for 5–10 min with 4.5–8.6% ethanol or 0.24–0.4% benzyl alcohol was found to induce parthenogenetic activation. Suppression of the second polar body with cytochalasin D and subsequent culture in vitro gave a high yield of parthenogenetic morulae and blastocysts (up to 85% overall). Fifty percent of transferred diploid parthenogenones implanted, 14% developed into egg cylinders, and 8% formed somites and developed as far as the forelimb-bud stage.

The interaction of waves and a turbulent current: waves propagating against the current

Abstract: The results of an experimental study of the interaction between waves and a current propagating in the same direction, have been reported by Kemp & Simons (1982). This paper describes the second part of the study, and considers the case of waves propagating against the current. Tests were performed in a laboratory flume with smooth and rough beds, and velocity measurements were made with a directionally sensitive laser anemometer as described in the previous paper. Analysis, including ensemble averaging of velocities and surface elevation, was performed by an on-line computer. Results indicate that the rate of wave attenuation is greatly increased by the addition of an opposing current, and reduced by a following current. Wave profiles remain closely described by Stokes second-order theory; orbital velocities are also found to be in agreement with a second-order wave theory modified to take account of the presence of the current. Certain results described occur regardless of the relative directions of current and wave. Mean velocities in the upper flow increase in the direction of the wave generator for increasing wave height. This suggests that the current is enhancing the wave-induced mass transport. Near the bed the velocity profiles so change that above the rough bed the current is retarded by the wave motion. In the logarithmic layer over the smooth bed velocities are increased with increasing wave height. However, all changes to velocity profiles have to be carefully interpreted, as the sidewall boundary layer decreases in thickness with even the smallest wave superimposed on the current. Turbulence intensities and Reynolds stresses near the rough bed are increased by the presence of the waves, most strongly in a layer two roughness heights above bed level, where fluctuations are periodic and effected by vortices ejected from the roughness troughs. Above this level, and over the smooth bed, turbulence levels are similar to those for the currents alone.