Search PubMed⌕ Search

Biomedical subjects

Keith Langley

Publications and source records attributed to Keith Langley.

18 recordsLinked to original sources
PubMed2007

Pyruvate modifies glycolytic and oxidative metabolism of rat embryonic spinal cord astrocyte cell lines and prevents their spontaneous transformation.

This study aimed to provide detailed data on mitochondrial respiration of normal astrocyte cell lines derived from rat embryonic spinal cord. Astrocytes in early passages (EP), cultured without pyruvate for more than 35 passages, defined here as late passages (LP), undergo spontaneous transformation. To study initial steps in cell transformation, EP data were compared with those of LP cells. LP cells had reduced glycolysis, fewer mitochondria and extremely low oxidative rates, resulting from a dysfunction of complexes I and II + III of the respiratory chain. Treatment of EP cells with pyruvate until they were, by definition, LP cultures prevented transformation of these cells. Pyruvate-treated EP cells had more mitochondria than normal cells but slightly lower respiratory rates. The increase of mitochondrial content thus appears to act as a compensatory effect to maintain oxidative phosphorylation in these LP 'non-transformed' cells, in which mitochondrial function is reduced. However, pyruvate treatment of transformed LP cells during additional passages did not significantly restore their oxidative metabolism. These data highlight changes accompanying spontaneous astrocyte transformation and suggest potential targets for the control of astrocyte proliferation and reaction to various insults to the central nervous system.

Aging↗
PubMed2006

Surface orientation, modulation frequency and the detection and perception of depth defined by binocular disparity and motion parallax.

Binocular disparity and motion parallax provide information about the spatial structure and layout of the world. Descriptive similarities between the two cues have often been noted which have been taken as evidence of a close relationship between them. Here, we report two experiments which investigate the effect of surface orientation and modulation frequency on (i) a threshold detection task and (ii) a supra-threshold depth-matching task using sinusoidally corrugated surfaces defined by binocular disparity or motion parallax. For low frequency corrugations, an orientation anisotropy was observed in both domains, with sensitivity decreasing as surface orientation was varied from horizontal to vertical. In the depth-matching task, for surfaces defined by binocular disparity the greatest depth was seen for oblique orientations. For surfaces defined by motion parallax, perceived depth was found to increase as surface orientation was varied from horizontal to vertical. In neither case was perceived depth for supra-threshold surfaces related to threshold performance in any simple manner. These results reveal clear differences between the perception of depth from binocular disparity or motion parallax, and between perception at threshold and supra-threshold levels of performance.

Cues↗
PubMed2006

Fine structural dependence of ultraviolet reflections in the King Penguin beak horn.

The visual perception of many birds extends into the near-ultraviolet (UV) spectrum and ultraviolet is used by some to communicate. The beak horn of the King Penguin (Aptenodytes patagonicus) intensely reflects in the ultraviolet and this appears to be implicated in partner choice. In a preliminary study, we recently demonstrated that this ultraviolet reflectance has a structural basis, resulting from crystal-like photonic structures, capable of reflecting in the near-UV. The present study attempted to define the origin of the photonic elements that produce the UV reflectance and to better understand how the UV signal is optimized by their fine structure. Using light and electron microscopic analysis combined with new spectrophotometric data, we describe here in detail the fine structure of the entire King Penguin beak horn in addition to that of its photonic crystals. The data obtained reveal a one-dimensional structural periodicity within this tissue and demonstrate a direct relationship between its fine structure and its function. In addition, they suggest how the photonic structures are produced and how they are stabilized. The measured lattice dimensions of the photonic crystals, together with morphological data on its composition, permit predictions of the wavelength of reflected light. These correlate well with experimentally observed values. The way the UV signal is optimized by the fine structure of the beak tissue is discussed with regard to its putative biological role.

Animal Communication↗
PubMed2005

Ultraviolet reflecting photonic microstructures in the King Penguin beak.

King and emperor penguins (Aptenodytes patagonicus and Aptenodytes forsteri) are the only species of marine birds so far known to reflect ultraviolet (UV) light from their beaks. Unlike humans, most birds perceive UV light and several species communicate using the near UV spectrum. Indeed, UV reflectance in addition to the colour of songbird feathers has been recognized as an important signal when choosing a mate. The king penguin is endowed with several highly coloured ornaments, notably its beak horn and breast and auricular plumage, but only its beak reflects UV, a property considered to influence its sexual attraction. Because no avian UV-reflecting pigments have yet been identified, the origin of such reflections is probably structural. In an attempt to identify the structures that give rise to UV reflectance, we combined reflectance spectrophotometry and morphological analysis by both light and electron microscopy, after experimental removal of surface layers of the beak horn. Here, we characterize for the first time a multilayer reflector photonic microstructure that produces the UV reflections in the king penguin beak.

Animal Communication↗
PubMed2005

Temporal adaptability and the inverse relationship to sensitivity: a parameter identification model.

Following a prolonged period of visual adaptation to a temporally modulated sinusoidal luminance pattern, the threshold contrast of a similar visual pattern is elevated. The adaptive elevation in threshold contrast is selective for spatial frequency, may saturate at low adaptor contrast, and increases as a function of the spatio-temporal frequency of the adapting signal. A model for signal extraction that is capable of explaining these threshold contrast effects of adaptation is proposed. Contrast adaptation in the model is explained by the identification of the parameters of an environmental model: the autocorrelation function of the visualized signal. The proposed model predicts that the adaptability of threshold contrast is governed by unpredicted signal variations present in the visual signal, and thus represents an internal adjustment by the visual system that takes into account these unpredicted signal variations given the additional possibility for signal corruption by additive noise.

Adaptation, Ocular↗
PubMed2004

Activation of the cGMP pathway in dopaminergic structures reduces cocaine-induced EGR-1 expression and locomotor activity.

Nitric oxide (NO) and the C-type natriuretic peptide (CNP) exert their action on brain via the cGMP signaling pathway. NO, by activating soluble guanylyl cyclase, and CNP, by stimulating membrane-bound guanylyl cyclase, cause intracellular increases of cGMP, activating cGMP-dependent protein kinases (PKGs). We show here that injection of CNP into the rat ventral tegmental area strongly reduced cocaine-induced egr-1 expression in the nucleus accumbens in a dose-dependent manner. The effect of CNP was reversed by the previous injection of a selective PKG inhibitor, KT5823. Activation of PKG by 8-bromo-cGMP reduced, like CNP, cocaine-induced gene transcription in dopaminergic structures. To confirm the involvement of PKG, this was overexpressed in either the mesencephalon or the caudate-putamen. Using the polyethyleneimine delivery system, an active protein was expressed by injecting a plasmid vector containing the human PKG-Ialpha cDNA. PKG was overexpressed in dopaminergic and GABAergic neurons when the plasmid was injected in the ventral tegmental area, whereas overexpression was observed in medium spiny GABAergic neurons and in both cholinergic and GABAergic interneurons when the PKG vector was injected into the caudate-putamen. Activation of the overexpressed PKG reduced cocaine-induced egr-1 expression in dopaminergic structures and affected behavior (i.e., locomotor activity). These effects were again reversed by previous injection of the selective PKG inhibitor. The current data suggest that NO and the neuropeptide CNP are potential regulators of cocaine-related effects on behavior.

Animals↗
PubMed2004

The hippocampal cholinergic neurostimulating peptide, the N-terminal fragment of the secreted phosphatidylethanolamine-binding protein, possesses a new biological activity on cardiac physiology.

Phosphatidylethanolamine-binding protein (PEBP), alternatively named Raf-1 kinase inhibitor protein, is the precursor of the hippocampal cholinergic neurostimulating peptide (HCNP) corresponding to its natural N-terminal fragment, previously described to be released by hippocampal neurons. PEBP is a soluble cytoplasmic protein, also associated with plasma and reticulum membranes of numerous cell types. In the present report, using biochemistry and cell biology techniques, we report for the first time the presence of PEBP in bovine chromaffin cell, a well described secretion model. We have examined its presence at the subcellular level and characterized this protein on both secretory granule membranes and intragranular matrix. In addition, its presence in bovine chromaffin cell and platelet exocytotic medium, as well as in serum, was reported showing that it is secreted. Like many other proteins that lack signal sequence, PEBP may be secreted through non-classic signal secretory mechanisms, which could be due to interactions with granule membrane lipids and lipid rafts. By two-dimensional liquid chromatography-tandem mass spectrometry, HCNP was detected among the intragranular matrix components. The observation that PEBP and HCNP were secreted with catecholamines into the circulation prompted us to investigate endocrine effects of this peptide on cardiovascular system. By using as bioassay an isolated and perfused frog (Rana esculenta) heart preparation, we show here that HCNP acts on the cardiac mechanical performance exerting a negative inotropism and counteracting the adrenergic stimulation of isoproterenol. All together, these data suggest that PEBP and HCNP might be considered as new endocrine factors involved in cardiac physiology.

Androgen-Binding Protein↗
PubMed2004

Expression of thyroid hormone receptor isoforms in the oligodendrocyte lineage.

Thyroid hormone (T3) regulates brain development and function and in particular ensures normal myelination. Animal models and in vitro systems have been employed to demonstrate the effects of T3, which acts via nuclear hormone receptors. T3 receptors (TRs) are transcription factors that activate or suppress target gene expression, such as myelin basic protein (MBP), in a hormone-dependent or -independent fashion. Two distinct genes, TR alpha and TR beta, encode several receptor isoforms with specific functions. This overview summarizes current knowledge on the cellular expression and the role of these isoforms and also examines the action of T3 on oligodendrocyte lineage cell types at defined developmental stages. Re-expression of TRs and also that of other transcription factors in oligodendrocytes may constitute some of the metabolic changes required for succesfull remyelination in the adult central nervous system after demyelinating lesions.

Animals↗
PubMed2002

Coexpression of thyroid hormone receptor isoforms in mouse oligodendrocytes.

Double and triple immunocytochemistry with stage-specific markers and specific antireceptor antibodies was used to study expression of nuclear thyroid hormone receptor (TR) isoforms in cultured mouse oligodendrocytes. To evaluate the coexpression of each TR isoform, antibodies were raised in rabbits and mice against specific regions of alpha1-TR and alpha2-TR common to both alpha isoforms and beta1-TR. Their specificities were assessed by Western blotting and by immunocytochemistry on rat hepatocytes. Oligodendrocyte subpopulations were found to coexpress the alpha- and beta1-TR epitopes at defined developmental stages. Both alpha- and beta1-TR isoforms are colocalized in oligodendrocytes during an early stage identified by the marker OL-1, before 2',3'-cyclic nucleotide 3'-phosphohydrolase is expressed. Expression of beta1-TR varies during maturation, and that of alpha-TR decreases during terminal maturation.

Aging↗
PubMed2002

The stereoscopic anisotropy: individual differences and underlying mechanisms.

Observers are more sensitive to variations in the depth of stereoscopic surfaces in a vertical than in a horizontal direction; however, there are large individual differences in this anisotropy. The authors measured discrimination thresholds for surfaces slanted about a vertical axis or inclined about a horizontal axis for 50 observers. Orientation and spatial frequency discrimination thresholds were also measured. For most observers, thresholds were lower for inclination than for slant and lower for orientation than for spatial frequency. There was a positive correlation between the 2 anisotropies, resulting from positive correlations between (a) orientation and inclination thresholds and (b) spatial frequency and slant thresholds. These results support the notion that surface inclination and slant perception is in part limited by the sensitivity of orientation and spatial frequency mechanisms.

Anisotropy↗
PubMed2002

Motion perception and motion estimation by total-least squares.

A computational model of motion perception is proposed. The model, which is gradient-based, adheres to the neural constraint that transmitted signals are positive-valued functions by posing the estimation of image motion as a quadratic programming problem combined with total-least squares: a model that assumes that image signals are contaminated by noise in both the spatial and temporal dimensions. By shrinking motion estimates with a regularizer whose subtractive effect introduces a contrast dependent speed threshold into motion computations, it is shown that the total-least squares model when posed as a quadratic programming problem, is capable of explaining both increases and decreases in perceived speed as these effects were reported by Thompson (1982) to vary as a function of image contrast and temporal frequency. The correlation that exists between the model's contrast speed response and results reported from visual psychophysics is consistent with the view that the visual system assumes that image signals may be contaminated by noise in both the spatial and the temporal domain, and that visual motion is influenced by the consequence of these assumptions.

Humans↗
PubMed2002

Contrast adaptation may enhance contrast discrimination.

Whether contrast adaptation may enhance contrast discrimination is a question that has remained largely unresolved because of conflicting empirical evidence. Greenlee and Heitger (1988), for example, reported that contrast discrimination may be enhanced after contrast adaptation, while Maattanen and Koenderink (1991) did not. This paper aimed to account for the different conclusions reached by these independent researchers by manipulations of key differences that exist between the two studies. It is shown that contrast discrimination may be enhanced after adaptation, but that these effects can vary markedly across subjects and test conditions. Enhancements in contrast discrimination are reported to be significant when adapting and testing at low levels of contrast, but just significant at higher levels of contrast. For high contrast signals; enhancements are shown to be independent of temporal frequency but dependent upon viewing conditions. Under binocular viewing conditions, enhancements in contrast discrimination thresholds are shown to be significantly higher than under monocular viewing conditions. It is suggested that the different conclusions reached by Greenlee and Heitger and by Maattanen and Koenderink may be explained by their respective differences in viewing conditions. The former study used binocular, while the latter study used monocular viewing with an occluding eyepatch.

Adaptation, Ocular↗
PubMed2002

A parametric account of contrast adaptation on contrast perception.

The effect of contrast adaptation on perceived contrast is assessed by contrast matching spatially adjacent sinusoidal gratings of similar spatial frequency, but different contrast and orientation. The main empirical question asked is why a high contrast orthogonal adaptor appears to amplify contrast signals through an increase in the slope of the contrast matching function but does not affect the threshold contrast at which a grating is detected. To explain this effect of adaptation, the Naka- Rushton receptor equation is employed as a description of the visual system's contrast response function. It is reported that the effects of adaptation may be described by three isotropic components, namely, signal amplification, division and addition, and one orientation specific component of subtraction. By collating the predictions made by the Naka-Rushton receptor equation with existing psychophysical data, it is shown that the magnitude of the isotropic components of adaptation increase with the contrast of the adapting signal. The orientation specific effect, however, is shown to saturate at relatively low adapting contrast levels. This saturation appears to be inconsistent with the commonly held view that the orientation specific effect represents a functional strategy used by the visual system to combat the problem of neural saturation in response firing rates.

Adaptation, Ocular↗
PubMed2002

Visual adaptation.

Explore the source record for details and available documents.

Adaptation, Ocular↗
PubMed1992

Noradrenergic, but not Adrenergic Chromaffin Cells in the Adrenal Gland Express Neuromodulin (GAP-43).

Neuroendocrine chromaffin cells of the adrenal gland express certain molecular markers either transiently during development or permanently. In the present study, the expression of neuromodulin (GAP-43), a neuronal protein often associated with neurite outgrowth, was examined in adult adrenals. Neuromodulin was detected by Western blot analysis in extracts of both rat adrenals and cultured bovine chromaffin cells, and was localized in situ in a subpopulation of chromaffin cells, as well as in nerve fibres and Schwann cells. The use of anti-tyrosine hydroxylase or anti-phenylethanolamine N-methyltransferase antibodies in combination with anti-neuromodulin antibodies in double immunofluorescent labelling of cryostat sections of rat glands demonstrated that neuromodulin is expressed by noradrenergic, and not by adrenergic chromaffin cells. The results provide further evidence that neuromodulin is not limited to neurons; it is also expressed in a subpopulation of neuroendocrine chromaffin cells. Neuromodulin may play a role in the development of the adrenal medulla or in the specific regulation of noradrenalin secretion from chromaffin cells.

Journal Article↗
PubMed1992

L1 Cell Adhesion Molecule is Expressed by Noradrenergic but not Adrenergic Chromaffin Cells: A Possible Major Role for L1 in Adrenal Medullary Design.

The adrenal medulla of higher animals is constituted of homotypic groups of chromaffin cells secreting either adrenalin or noradrenalin. Since not all chromaffin cells are individually innervated by fibres of the splanchnic nerve, this tissue characteristic is crucial to the physiological function of the gland. In an attempt to analyse differences between these chromaffin cell types which might underlie the establishment of this tissue pattern, we examined the expression of the adhesion molecule L1 in this gland by immunocytochemistry at the optical and ultrastructural levels in rats. L1, an adhesion molecule abundant in the central nervous system, was found to be present in the adrenal medulla of adults; it was strongly expressed on innervating axons and their surrounding Schwann cells and also on a subpopulation of chromaffin cells. The nature of these chromaffin cells was examined by immunocytochemistry using antibodies against the catecholamine-synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT), which are capable of distinguishing between adrenergic and noradrenergic cells. Immunofluorescence labelling of sequential frozen sections demonstrated that chromaffin cells which express L1 do not express PNMT; conversely, L1 was not detected in any chromaffin cells expressing PNMT. Ultrastructural immunocytochemistry confirmed the existence of two non-overlapping populations of chromaffin cells. It is concluded that, in the adrenal medulla, noradrenergic but not adrenergic chromaffin cells express this adhesion molecule. These data, together with our previous observations that all chromaffin cells express the neural cell adhesion molecule, NCAM, suggest that L1, in cooperation with NCAM, could be responsible for the association of noradrenergic cells in the form of homotypic aggregates segregated from groups of adrenergic cells within the adrenal medulla.

Journal Article↗
PubMedDate not supplied

7beta-hydroxycholesterol blocked at C-3-OH inhibits growth of rat glioblastoma in vivo: comparison between 7beta-hydroxycholesteryl-3beta (ester)-oleate and 7beta-hydroxycholesteryl-3-beta-O (ether)-oleyl.

BACKGROUND: It was previously demonstrated that the 7beta-hydroxycholesteryl-3beta(ester)-oleate (7beta-ester) possesses antitumor properties against the experimental rat C6 glioblastoma. The effect of an analog of this molecule, 7beta-hydroxycholesterol-3beta-O(ether)-oleyl (7beta-ether), was investigated. MATERIALS AND METHODS: Liposomes containing no oxysterol (control), 7beta-ether or 7beta-ester were injected into tumors induced by C6 cells in rat brain cortex. At defined times, the animals were sacrificed, the tumors stained with cresyl violet and their volumes measured by densitometry. Oxysterol clearance was assessed by quantification from lipid extraction of treated tumors. RESULTS: The clearance of the new compound was slower than that of the 7beta-ester form. The 7beta-ether and 7beta-ester forms displayed similar antitumor activities against 3-day-old tumors. In contrast, the 7beta-ether form was more active on well-developed glioblastoma: 75 nmol inhibited tumor growth by 70% compared to controls, while the 7beta-ester had no effect under such conditions. The 7beta-ether form had a cytostatic rather than a cytotoxic effect. In addition, the composition of the liposomes did not affect the antitumor activity. CONCLUSION: Only blockade of the C-3-OH group is required for the antitumor effect of this kind of oxysterol. It is suggested that the absence of "etherases" enhances the antitumor activity of this type of compound. Thus, an original therapeutic approach for glioblastoma treatment may be envisaged with such compounds.

Animals↗