Showing papers by "University College London published in 1985"
TL;DR: Differences in the structure of the P2-purinoceptor in various tissues may be useful in the development of drugs for the treatment of vascular, gastrointestinal and urinoglenital disorders.
Abstract: 1. 1.|It is suggested that the P2-purinoceptor may be separated into two subtypes largely on the basis of the rank order of agonist potency of structural analogues of ATP and also on the activity of antagonists at the P2-purinoceptor: Subtype 1 (designated P2X) 2. (i)|potency order: α,β-methyleneATP, β,γ-methyleneATP > ATP = 2 methylthioATP; 3. (ii)|antagonism by ANAPP3 and selectively desensitisation following administration of α,β-methyleneATP; 4. (iii)|present in the vas deferens and urinary bladder of guinea-pig and rat, frog and rat ventricle, and also in the smooth muscle of the rat femoral artery and rabbit central ear artery, where they mediate excitation. Subtype 2 (designated P2Y) 5. (i)|potency order: 2-methylthioATP ⪢ ATP > α,β-methyleneATP, β,γ-methyleneATP; 6. (ii)|weak antagonism by ANAPP3 and desensitisation following administration of α,β-methyleneATP; 7. (iii)|present in the guinea-pig taenia coli and the longitudinal muscle layer of the rabbit portal vein, where they mediate relaxation, and also on the vascular endothelial cells of the rat femoral artery and pig aorta (where occupation leads to the production of endothelium-derived relaxing factor). 8. 2.|Differences in the structure of the P2-purinoceptor in various tissues may be useful in the development of drugs for the treatment of vascular, gastrointestinal and urinoglenital disorders.
1,324 citations
TL;DR: In this article, the authors present a systematic approach to the derivation of empirical potential parameters for binary oxides; they also consider their modification for use in mixed oxide systems, and discuss successful applications of the potentials to the calculation of perfect lattice properties.
Abstract: The authors present a systematic approach to the derivation of empirical potential parameters for binary oxides; they also consider their modification for use in mixed oxide systems. Shell-model potentials are used but, unlike the case of the alkali halides within which polarisability and short-range interaction parameters can be transferred, modifications must be introduced when transferring potential parameters between different oxides. The anion polarisability varies with structure and with the nature of the host cation, and changes in cation coordination are reflected in the short-range repulsive cation-anion interaction. Parameters are derived for a range of oxides, and trends in these parameters are discussed. They discuss successful applications of the potentials to the calculation of perfect lattice properties. Equal success is enjoyed when defect and surface properties are considered; in particular the models correctly predict the activation energies for dopant diffusion in NiO, and to a large extent model the surface rumpling of MgO.
1,035 citations
TL;DR: Evidence that mast cell secretion is inhibited by internalized neomycin, a compound known to interact with PPI, and the PPI phosphodiesterase of human neutrophil plasma membranes can be activated simply by adding GTP analogues in the presence of concentrations of Ca2+ that pertain in unstimulated cells are provided.
Abstract: Interaction of ligands with ‘Ca2+-mobilizing’ receptors is thought to result in the generation of two second messengers, inositol trisphosphate and diacylglycerol, from a common substrate, phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (refs 1, 2), a component of plasma membranes3,4. It is not known how the occupation of such receptors is translated into the activation of the catalytic unit polyphosphoinositide (PPI) phosphodiesterase, and then to cellular activation, but our recent experiments suggest that GTP regulatory proteins may be involved. In mast cells, non-hydrolysable analogues of GTP introduced and then trapped in the cytosol are able to substitute for external ligands in inducing exocytosis, a well-defined Ca2+-dependent process5, suggesting that guanine nucleotide regulatory proteins may act by stimulating the catalytic activity of the PPI phosphodiesterase. We now provide evidence that mast cell secretion is inhibited by internalized neomycin, a compound known to interact with PPI6. We also show that the PPI phosphodiesterase of human neutrophil plasma membranes can be activated simply by adding GTP analogues in the presence of concentrations of Ca2+ that pertain in unstimulated cells. These findings strongly support the idea that the coupling factor linking receptor and PPI phosphodiesterase is a guanine nucleotide binding protein analogous to those involved in the activation and inhibition of adenylate cyclase7.
863 citations
TL;DR: In this paper, the authors summarized the present knowledge about the mechanisms involved in the control of the phenotypic expression of mammalian muscle fibers and discussed how the activity imposed on the muscle fibers by the motoneuron finally induces in the muscle cells the expression of those genes that define its particular phenotype.
Abstract: In this review, the present knowledge about the mechanisms involved in the control of the phenotypic expression of mammalian muscle fibers is summarized. There is a discussion as to how the activity imposed on the muscle fibers by the motoneuron finally induces in the muscle cells the expression of those genes that define its particular phenotype. The functional and molecular heterogeneity of skeletal muscle is thus defined by the existence of motor units with varied function, while the homogeneity of muscle fibers belonging to the same motor unit is yet another indication of the importance of activity in the control of gene expression of the mammalian muscle fiber.
728 citations
TL;DR: There is good evidence that changes in the calcium supply to the myofibrils can account for the slow changes in tension that follow an alteration in length; there may also be rapid changes in calcium supply but this is less clearly established at present.
584 citations
TL;DR: Lesions of the anterior interpositus nucleus (IA) abolished NMR conditioning to light and white noise stimuli on the side of the lesion without affecting unconditional responses in 20 rabbits as mentioned in this paper.
Abstract: The classically conditioned nictitating membrane response (NMR) of the rabbit, a simple form of associative motor learning, is crucially dependent upon the cerebellum. Discrete unilateral lesions of the cerebellar nuclei were made in 20 rabbits. Lesions of the anterior interpositus nucleus (IA) abolished NMR conditioning to light and white noise stimuli on the side of the lesion without affecting unconditional responses. Lesions of the posterior interpositus nucleus, fastigial and dentate nuclei were without effect upon NMR conditioning.
528 citations
TL;DR: The results are discussed in relation to the possible functions of the corticopontine system, especially the role of the extrastriate visual areas in visually guided movement.
Abstract: The distribution of cortical cells projecting to the pontine nuclei in rats was studied by making large injections of horseradish peroxidase that filled the basilar pons and measuring the density of labelled cells in each cortical area. All retrogradely labelled cells were layer V pyramidal cells. The highest densities of labelled cells were observed in the motor areas. The lowest densities were in temporal association cortex and perirhinal cortex. Visual cortical areas, including the primary visual cortex, provided a major source of pontine projections. The distribution of corticopontine cells within the primary visual cortex was studied in more detail. In all cases the highest density of labelled cells was observed in the region of cortex that represents the nasal visual field. Control injections into brainstem regions adjacent to the pontine nuclei produced a much lower absolute density of retrogradely labelled cortical cells and the distribution of those cells was different from that observed following pontine injections. We conclude that every area of the rat's cerebral cortex projects to the pontine nuclei and that there are consistent variations in the density of the projections both between and within areas.
500 citations
TL;DR: The structure of the interface between VL and VH domains in three immunoglobulin fragments is analyzed and the 12 residues that form the central part of the three observed VL-VH packings are absolutely or very strongly conserved in all immunoglobia sequences.
494 citations
TL;DR: Transganglionic transport of wheatgerm agglutinin conjugated horseradish peroxidase was used to reveal the central distribution of terminals of primary afferent fibers from peripheral nerves innervating the hind leg of the rat.
Abstract: Transganglionic transport of wheatgerm agglutinin conjugated horse-radish peroxidase (WGA-HRP) was used to reveal the central distribution of terminals of primary afferent fibers from peripheral nerves innervating the hind leg of the rat. In separate experiments the sizes and locations of cutaneous peripheral receptive fields were determined by electrophysiological recording techniques for each of the nerves that had been labeled with WGA-HRP. By using digital image analysis, the sizes and positions of the peripheral receptive fields were correlated with the areas of superficial dorsal horn occupied by terminals of primary afferents from each of these receptive fields. Data were obtained from the posterior cutaneous nerve of the thigh, lateral sural, sural, saphenous, superficial peroneal, and tibial nerves. The subdivisions of the sciatic nerve, the sural, lateral sural, superficial peroneal, and tibial nerves each projected to a separate and distinct region of the superficial dorsal horn and collectively formed a "U"-shaped zone of terminal labeling extending from lumbar spinal segments L2 to the caudal portions of L5. The gap in the "U" extended from L2 to the L3-4 boundary and was occupied by terminals from the saphenous nerve. Collectively, all primary afferents supplying the hindlimb occupied the medial 3/4 of the superficial dorsal horn with terminals from the tibial nerve lying most medially and occupying the largest of all the terminal fields. Afferents from the superficial peroneal lay in a zone between the medially situated tibial zone and the more laterally placed sural zone. Afferents from the posterior cutaneous nerve were located most caudally and laterally. Terminal fields from the posterior cutaneous and saphenous nerves differed from the others in having split representations caused presumably by their proximity to the mid-axial line of the limb. Comparisons between the peripheral and the central representations of each nerve revealed that 1 mm2 of surface area of the superficial dorsal horn serves approximately 600-900 mm2 of hairy skin and roughly 300 mm2 of glabrous skin. The vast majority of terminal labeling observed in the dorsal horn was found in the marginal layer and substantia gelatinosa, suggesting that small diameter afferents have an orderly somatotopic arrangement in which each portion of the skin surface is innervated by afferent fibers that terminate in preferred localities within the dorsal horn.
455 citations
TL;DR: It is reported that V4 and V5 are connected with separate cytochrome oxidase-defined subregions of V2, suggesting that cortical pathways dealing with motion and colour perception are segregated in their passage through V1, and reinforcing evidence for functional specialization in the visual cortex.
Abstract: V5 and V4 are areas of macaque monkey prestriate visual cortex that are specialized for involvement in different aspects of visual perception, namely motion for V5 (refs 1-4) and colour vision, with other possible functions, for V4 (refs 2, 5-9). Thus, it is unlikely that they should be fed the same information for further processing, yet both receive a strong input from patches of the upper layers of V2 (refs 10, 11), the area immediately adjoining the primary visual cortex, V1. V2, however, seems to comprise functionally distinct subregions, which can be revealed by staining the tissue for the mitochondrial enzyme cytochrome oxidase. Here we report that V4 and V5 are connected with separate cytochrome oxidase-defined subregions of V2, suggesting that cortical pathways dealing with motion and colour perception are segregated in their passage through V2, and reinforcing evidence for functional specialization in the visual cortex.
446 citations
TL;DR: In this article, a comparison between couleurs synthetiques and indices de photometrie is made for des atmospheres stellaires modeles avec les couleur and indices observes for des etoiles B, A, and F.
Abstract: Comparaison des couleurs synthetiques et des indices de photometrie uvbyβ calcules pour des atmospheres stellaires modeles avec les couleurs et indices observes pour des etoiles B, A et F dont on connait T eff et log g
TL;DR: MIRAGE, a theory for the primitive coding of the (1D) spatial distribution of luminance changes by the human visual system is developed from a theoretical examination of the practical problems associated with the characterization of such changes.
TL;DR: Evaluating the usefulness of enamel thickness and microstructure as characteristics for determining the relationships of the later Miocene hominoids is evaluated, based both on a quantitative study ofEnamel thickness in extant hominoid and four species of laterMiocene Sivapithecus (including ‘Ramapitalcus’) and on scanning electron microscope analysis of enameling microst structure.
Abstract: Enamel thickness has assumed unique importance in the debate about the hominid status of Ramapithecus, despite the fact that there is little agreement about the meaning of ‘thick enamel’ or the significance of enamel thickness for hominoid taxonomy1–19. My aim here is to evaluate the usefulness of enamel thickness and microstructure as characteristics for determining the relationships of the later Miocene hominoids, based both on a quantitative study of enamel thickness in extant hominoids and four species of later Miocene Sivapithecus (including ‘Ramapithecus’) and on scanning electron microscope analysis of enamel microstructure20. Four categories of enamel thickness are defined metrically here and have been related to enamel microstructure and developmental rates. Thin fast-formed (pattern 3) enamel represents the ancestral condition in hominoids; it increased developmentally to thick pattern 3 enamel in the great ape and human clade and that condition is primitively retained in Homo and in the fossil hominoid Sivapithecus (including ‘Ramapithecus’). Enamel thickness has been secondarily reduced in the African apes and also, although at a different rate and extent, in the orang-utan. Thick enamel, previously the most important characteristic in arguments about the earliest hominid, does not therefore identify a hominid.
TL;DR: Lymphoma complicating coeliac disease appears to be of T-cell, rather than histiocyte, origin.
TL;DR: It is shown for the first time that Plio-Pleistocene hominids had markedly abbreviated growth periods relative to modern man, similar to those of the modern great apes.
Abstract: We report here revised chronological ages at death of immature fossil hominids demonstrating for the first time that Plio-Pleistocene hominids had markedly abbreviated growth periods relative to modern man, similar to those of the modern great apes. Previous estimates of age at death for fossil hominids have principally been based on dental eruption, maturation and dental wear criteria for modern man and hence reflect their age in 'human' years. We are now able to estimate the absolute duration of permanent incisor crown formation by observing gross incremental growth features in enamel and thereby apply a timescale to dental developmental events for specimens representing four Plio-Pleistocene fossil hominid taxa. Thus we have derived more reliable-species-specific-estimates of age at death that provide a more secure model on which to base studies of the palaeodemography, growth and maturation of early hominids.
TL;DR: In this article, the authors used three antibodies (anti-galactocerebroside (GC), anti-glial fibrillary acidic protein (GFAP), and the A2B5 monoclonal antibody) to examine the timing and sequence of the development of the three types of glial cells in vivo.
TL;DR: In this article, an energy-based method of calculating elastic-plastic strains and stresses near notches and cracks is presented, where the strain energy density in the plastic zone ahead of a notch can be calculated on the basis of the elastic stress-strain solution.
TL;DR: The findings suggest that the timing of oligodendrocyte differentiation depends on an intrinsic clock in the O-2A progenitor cell that counts cell divisions that are driven by a growth factor (or factors) produced by type 1 astrocytes.
TL;DR: In this paper, the authors describe some aspects of reading and writing in a highly literate subject who has unusual difficulty in reading and spelling non-words, and no cerebral trauma is indicated.
Abstract: This paper describes some aspects of reading and writing in a highly literate subject who has unusual difficulty in reading and spelling non-words. No cerebral trauma is indicated, and she performs...
TL;DR: In this paper, an application of the equivalent strain energy density method for calculation of elastic-plastic notch-tip strain under cyclic loading is presented. But the energy density was not applied to the case of the plastic yielding around the notch tip.
TL;DR: In this paper, the pressure drop correlation was proposed on the basis of theoretical considerations and compared with published experimental results obtained from high voidage fixed beds of spheres and is shown to represent a significant improvement over the established Ergun equation, which is used to produce drag coefficient correlations for individual particles in the bed which in turn yield a general and fully predictive expression for the drag force on a particle in a fluidized suspension.
TL;DR: In this paper, a method of multiplexing several optical signals onto a single spatial channel using a short coherence length continuous wave light source is described, and some design considerations are discussed Experimental results for a single sensor and receiver are presented and compared with theoretical predictions.
Abstract: This paper describes a method of multiplexing several optical signals onto a single spatial channel (eg, a single-mode fiber) using a short coherence length continuous wave light source Several system configurations which utilize this technique are proposed, and some design considerations are discussed Experimental results for a single sensor and receiver are presented and compared with theoretical predictions
TL;DR: It is shown that 0-2A progenitor cells can differentiate into type-2 astrocytes or oligodendroCytes when grown as isolated cells in microculture, indicating that differentiation along either glial pathway in vitro does not require signals from other CNS cells, apart from the signals provided by components of the culture medium.
Abstract: Although it is known that most cells of the vertebrate central nervous system (CNS) are derived from the neuroepithelial cells of the neural tube (reviewed in ref. 1), the factors determining whether an individual neuroepithelial cell develops into a particular type of neurone or glial cell remain unknown. A promising model for studying this problem is the bipotential glial progenitor cell in the developing rat optic nerve; this cell differentiates into a particular type of astrocyte (a type-2 astrocyte2) if cultured in 10% fetal calf serum (FCS) and into an oligodendrocyte if cultured in serum-free medium3. As the oligodendrocyte–type-2 astrocyte (0-2A) progenitor cell can differentiate along either glial pathway in neurone-free cultures2,4, living axons clearly are not required for its differentiation, at least in vitro. However, the studies on 0-2A progenitor cells were carried out in bulk cultures of optic nerve, and so it was possible that other cell–cell interactions were required for differentiation in culture. We show here that 0-2A progenitor cells can differentiate into type-2 astrocytes or oligodendrocytes when grown as isolated cells in microculture, indicating that differentiation along either glial pathway in vitro does not require signals from other CNS cells, apart from the signals provided by components of the culture medium. We also show that single 0-2A progenitor cells can differentiate along either pathway without dividing, supporting our previous studies using 3H-thymidine3 and suggesting that DNA replication is not required for these cells to choose between the two differentiation programmes.
TL;DR: The cellular and synaptic organization of the TRN in adult albino rats on the basis of LM and EM studies of normal animals and experimental animals with injections of horseradish peroxidase (HRP) and/or lesions in various parts of the brain is described.
Abstract: The thalamic reticular nucleus (TRN) is a sheet-like nucleus partially enclosing the dorsolateral and anterior aspects of the thalamus and traversed by the thalamo-cortical and cortico-thalamic fibre systems This paper describes the cellular and synaptic organization of the TRN in adult albino rats on the basis of LM and EM studies of normal animals and experimental animals with injections of horseradish peroxidase (HRP) and/or lesions in various parts of the brain Particular attention was paid to the dorso-caudal part of the TRN, which establishes connections with visual centres
TL;DR: Radioimmunoassay of substance P revealed that chronic NGF treatment of a cut sciatic nerve does partially reverse the central changes that normally follow deafferentation.
TL;DR: A selective lack of the enhanced phosphorylation of a protein of relative molecular mass (Mr) 44,000 (44K) that was observed in normal subjects and in two CGD patients with an X-linked inheritance could be an important functional component of the oxidase.
Abstract: Phagocytosing neutrophils, monocytes, macrophages and eosinophils produce a burst of non-mitochondrial respiration that is important for the killing and digestion of microbes. Much of the information about the oxidase system involved comes from studies on patients with chronic granulomatous disease (CGD), a syndrome in which an undue predisposition to infection results from complete absence of this burst of stimulated respiratory activity. The basis of the oxidase activity is an electron transport chain, the only established component of which is a very unusual b-type cytochrome (b-245) (ref. 2). The molecular defect in the X-linked subgroup of CGD is the absence of this cytochrome b-245, which, however, appears to be normal in those subjects with the autosomal recessive mode of inheritance. In an attempt to identify an abnormality of activation, or an absence or malfunction of a proximal component of the electron transport chain in this latter group, we examined protein phosphorylation in neutrophils after activation of the oxidase with phorbol myristate acetate. All four of the patients studied demonstrated a selective lack of the enhanced phosphorylation of a protein of relative molecular mass (Mr) 44,000 (44K) that was observed in normal subjects and in two CGD patients with an X-linked inheritance. This molecule, therefore, could be an important functional component of the oxidase.
TL;DR: In this paper, a functional model for the development of overseas student friendship patterns was presented, where subjects were asked to specify various aspects (including nationality) of their three best friends, and also their preferred companion for each of a range of everyday situations.
Abstract: The aim of this study was to replicate and extend the study of Bochner et al. (1977) which presented a functional model for the development of overseas student friendship patterns. Whereas Bochner et al. (1977) used only 30 Far Eastern foreign students and 6 host nationals in his Hawaian study, this study used 140 foreign students from each continent. Subjects were asked to specify various aspects (including nationality) of their three best friends, and also their preferred companion for each of a range of everyday situations. The friendship network data revealed a strong preference for co-national friends first, other nationals second and host nationals third, while the preferred companion data showed co-nationals first, then host nationals and finally ‘other’ nationals. The results closely match the results of Bochner et al. (1977) and provide further evidence for the functional model.
TL;DR: Results demonstrate that the systemic administration of drugs which increase the inactivation of sodium channels can produce a selective central block of certain types of afferent evoked activity in the spinal cord.
Abstract: An electrophysiological analysis of the antinociceptive effects of systemic lidocaine and its longer acting primary amine congener, tocainide, has been performed in the decerebrate-spinal unanaesthetised rat. Neither of these local anaesthetic drugs when administered systemically in doses of up to 10 mg/kg (lidocaine) or 100 mg/kg (tocainide), produced any evidence of a block in the conduction of action potentials in A beta, A delta or C primary afferents. The local anaesthetics also failed to reduce mustard oil induced neurogenic extravasation, a test of cutaneous C-fibre terminal function. Lidocaine produced a transient (1-2 min) depression in monosynaptic reflexes at doses of greater than or equal to 1 mg/kg while tocainide had no effect on this reflex at any dose up to a 100 mg/kg. Both drugs, however, significantly suppressed the C-fibre evoked polysynaptic reflex generated by stimulating the sural nerve. The tocainide effect was longer lasting with less action on the short latency A beta-evoked reflex than lidocaine. The reflex activity in hamstring flexor alpha-motoneurones evoked by pinching the toes of the ipsilateral hind paw was reduced by both drugs but not abolished. Thermal and noxious chemical evoked reflexes were, however, completely suppressed by the local anaesthetic drugs, again with a longer action from tocainide. These results demonstrate that the systemic administration of drugs which increase the inactivation of sodium channels can produce a selective central block of certain types of afferent evoked activity in the spinal cord. There are resemblances between the selective C-fibre suppressing actions of systemically administered local anaesthetic and the pharmacological actions of narcotic opiates which may represent a similar mechanism for the analgesic action of these quite different classes of drugs.
TL;DR: In this paper, it was shown that the root mean square (rms) value of the intensity fluctuations is dependent on the scattering coefficient of the particles and the square root of their concentration.
TL;DR: It is concluded that specific and theoretically motivated treatment methods can cause significant improvement in the word retrieval ability of patients with chronic aphasia.
Abstract: The effects of two therapy methods in the treatment of picture naming problems are compared, using a within-patient design with 12 adult patients with chronic acquired aphasia. We contrast techniques that require the patient to process the meaning corresponding to the picture name (semantic treatment) with those that provide the patients with information about the phonological form of the name (phonological treatment). With each method, patients either had 4 sessions of treatment over one week, or 8 sessions over two weeks. Both methods caused day-by-day improvement that was specific to the actual items treated. Both methods resulted in significant improvement in naming when this was measured one week after the end of treatment, with a small, but significant advantage for the semantic treatment; this is mainly due to improvement that generalizes to untreated items. We conclude that specific and theoretically motivated treatment methods can cause significant improvement in the word retrieval ability of patients with chronic aphasia.