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Sample records for general epithelial innervation

  1. The human periodontal membrane: focusing on the spatial interrelation between the epithelial layer of Malassez, fibers, and innervation

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    Kjaer, Inger; Nolting, Dorrit

    2009-01-01

    OBJECTIVE: The purpose of the present study was to map the spatial interrelation of fibers, peripheral nerves, and epithelial layer of Malassez in human periodontal membrane in areas close to the root surfaces. MATERIAL AND METHODS: Four healthy permanent teeth extracted from four patients during...

  2. SOLITARY CHEMORECEPTOR CELL SURVIVAL IS INDEPENDENT OF INTACT TRIGEMINAL INNERVATION

    Science.gov (United States)

    Gulbransen, Brian; Silver, Wayne; Finger, Tom

    2008-01-01

    Nasal solitary chemoreceptor cells (SCCs) are a population of specialized chemosensory epithelial cells presumed to broaden trigeminal chemoreceptivity in mammals (Finger et al., 2003). SCCs are innervated by peptidergic trigeminal nerve fibers (Finger et al., 2003) but it is currently unknown if intact innervation is necessary for SCC development or survival. We tested the dependence of SCCs on innervation by eliminating trigeminal nerve fibers during development with neurogenin-1 knockout mice, during early postnatal development with capsaicin desensitization, and during adulthood with trigeminal lesioning. Our results demonstrate that elimination of innervation at any of these times does not result in decreased SCC numbers. In conclusion, neither SCC development nor mature cell maintenance is dependent on intact trigeminal innervation. PMID:18300260

  3. Epithelial transport in The Journal of General Physiology.

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    Palmer, Lawrence G

    2017-10-02

    Epithelia define the boundaries of the body and often transfer solutes and water from outside to inside (absorption) or from inside to outside (secretion). Those processes involve dual plasma membranes with different transport components that interact with each other. Understanding those functions has entailed breaking down the problem to analyze properties of individual membranes (apical vs. basolateral) and individual transport proteins. It also requires understanding of how those components interact and how they are regulated. This article outlines the modern history of this research as reflected by publications in The Journal of General Physiology . © 2017 Palmer.

  4. Peripheral innervation patterns of vestibular nerve afferents in the bullfrog utriculus

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    Baird, Richard A.; Schuff, N. R.

    1994-01-01

    Vestibular nerve afferents innervating the bullfrog utriculus differ in their response dynamics and sensitivity to natural stimulation. They also supply hair cells that differ markedly in hair bundle morphology. To examine the peripheral innervation patterns of individual utricular afferents more closely, afferent fibers were labeled by the extracellular injection of horseradish peroxidase (HRP) into the vestibular nerve after sectioning the vestibular nerve medial to Scarpa's ganglion to allow the degeneration of sympathetic and efferent fibers. The peripheral arborizations of individual afferents were then correlated with the diameters of their parent axons, the regions of the macula they innervate, and the number and type of hair cells they supply. The utriculus is divided by the striola, a narrow zone of distinctive morphology, into media and lateral parts. Utiricular afferents were classified as striolar or extrastriolar according to the epithelial entrance of their parent axons and the location of their terminal fields. In general, striolar afferents had thicker parent axons, fewer subepithelial bifurcations, larger terminal fields, and more synaptic endings than afferents in extrstriolar regions. Afferents in a juxtastriolar zone, immediately adjacent to the medial striola, had innervation patterns transitional between those in the striola and more peripheral parts of the medial extrastriola. moast afferents innervated only a single macular zone. The terminal fields of striolar afferents, with the notable exception of a few afferents with thin parent axons, were generally confined to one side of the striola. Hair cells in the bullfrog utriculus have perviously been classified into four types based on hair bundle morphology. Afferents in the extrastriolar and juxtastriolar zones largely or exclusively innervated Type B hair cells, the predominant hair cell type in the utricular macula. Striolar afferents supplied a mixture of four hair cell types, but largely

  5. Autonomic cardiac innervation

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    Hasan, Wohaib

    2013-01-01

    Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these “non-classical” cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development.   Cardiac autonomic nerves are closely spatially associated in cardiac plexuses, ganglia and pacemaker regions and so are sensitive to release of neurotransmitter, neuropeptides and trophic factors from adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within the two arms of the autonomic system that is critical for disease progression. Although this crosstalk between sympathetic and parasympathetic nerves has been well established for adult nerves, it is unclear whether a degree of paracrine regulation occurs across the autonomic limbs during development. Aberrant nerve remodeling is a common occurrence in many adult cardiovascular pathologies, and the mechanisms regulating outgrowth or denervation are disparate. However, autonomic neurons display considerable plasticity in this regard with neurotrophins and inflammatory cytokines having a central regulatory

  6. Immunomodulation stimulates the innervation of engineered tooth organ.

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    Tunay Kökten

    Full Text Available The sensory innervation of the dental mesenchyme is essential for tooth function and protection. Sensory innervation of the dental pulp is mediated by axons originating from the trigeminal ganglia and is strictly regulated in time. Teeth can develop from cultured re-associations between dissociated dental epithelial and mesenchymal cells from Embryonic Day 14 mouse molars, after implantation under the skin of adult ICR mice. In these conditions however, the innervation of the dental mesenchyme did not occur spontaneously. In order to go further with this question, complementary experimental approaches were designed. Cultured cell re-associations were implanted together with trigeminal ganglia for one or two weeks. Although axonal growth was regularly observed extending from the trigeminal ganglia to all around the forming teeth, the presence of axons in the dental mesenchyme was detected in less than 2.5% of samples after two weeks, demonstrating a specific impairment of their entering the dental mesenchyme. In clinical context, immunosuppressive therapy using cyclosporin A was found to accelerate the innervation of transplanted tissues. Indeed, when cultured cell re-associations and trigeminal ganglia were co-implanted in cyclosporin A-treated ICR mice, nerve fibers were detected in the dental pulp, even reaching odontoblasts after one week. However, cyclosporin A shows multiple effects, including direct ones on nerve growth. To test whether there may be a direct functional relationship between immunomodulation and innervation, cell re-associations and trigeminal ganglia were co-implanted in immunocompromised Nude mice. In these conditions as well, the innervation of the dental mesenchyme was observed already after one week of implantation, but axons reached the odontoblast layer after two weeks only. This study demonstrated that immunodepression per se does stimulate the innervation of the dental mesenchyme.

  7. Peribronchial innervation of the rat lung.

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    Artico, Marco; Bosco, Sandro; Bronzetti, Elena; Felici, Laura M; Pelusi, Giuseppe; Lo Vasco, Vincenza Rita; Vitale, Marco

    2004-10-01

    Mammalian peribronchial tissue is supplied by several peptide-containing nerve fibers. Although it is well established that different neuropeptides exert significant effects on bronchial and vascular tone in the lungs, the role played by some neuromediators on the general regulation, differentiation and release of locally active substances is still controversial. We studied the innervation of rat peribronchial tissue by immunohistochemical techniques. The immunoperoxidase method with nickel amplification was applied to detect the distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was studied by immunohistochemistry. A slight immunoreactivity for NT receptors is observed in lung bronchial epithelium. There is increasing evidence that NTs may act with a paracrine mechanism regulating functional activity of neuronal and non-neuronal structures. A specific immunoreactivity for NTs and NT receptors was also demonstrated within different layers of large, medium and small sized intrapulmonary arteries and veins, according to a recent study of our group. Moreover our data describe the expression of NTs and NT receptors in lymphoid aggregates of the lung (BALT) in which both lymphocytes and macrophages express TrkA receptor and synthesize NTs. Our results show the presence of an extensive network of innervation in the rat peribronchial tissue, confirming a morphological basis for a possible neural modulation of the respiratory mucosa and the physiological/pathophysiological mechanisms of the lung.

  8. Netrin-1 controls sympathetic arterial innervation.

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    Brunet, Isabelle; Gordon, Emma; Han, Jinah; Cristofaro, Brunella; Broqueres-You, Dong; Liu, Chun; Bouvrée, Karine; Zhang, Jiasheng; del Toro, Raquel; Mathivet, Thomas; Larrivée, Bruno; Jagu, Julia; Pibouin-Fragner, Laurence; Pardanaud, Luc; Machado, Maria J C; Kennedy, Timothy E; Zhuang, Zhen; Simons, Michael; Levy, Bernard I; Tessier-Lavigne, Marc; Grenz, Almut; Eltzschig, Holger; Eichmann, Anne

    2014-07-01

    Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type-specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs.

  9. Noradrenergic and cholinergic innervation of the bone marrow.

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    Artico, Marco; Bosco, Sandro; Cavallotti, Carlo; Agostinelli, Enzo; Giuliani-Piccari, Gabriella; Sciorio, Salvatore; Cocco, Lucio; Vitale, Marco

    2002-07-01

    Bone marrow is supplied by sensory and autonomic innervation. Although it is well established that hematopoiesis is regulated by cytokines and cell-to-cell contacts, the role played by neuromediators on the proliferation, differentiation and release of hematopoietic cells is still controversial. We studied the innervation of rat femur bone marrow by means of fluorescence histochemistry and immunohistochemistry. Glyoxylic acid-induced fluorescence was used to demonstrate catecholaminergic nerve fibers. The immunoperoxidase method with nickel amplification was applied to detect the distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was studied by immunohistochemistry. Our results show the presence of an extensive network of innervation in the rat bone marrow, providing a morphological basis for the neural modulation of hemopoiesis.

  10. Innervation of the mammalian esophagus.

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    Neuhuber, Winfried L; Raab, Marion; Berthoud, Hans-Rudolf; Wörl, Jürgen

    2006-01-01

    Understanding the innervation of the esophagus is a prerequisite for successful treatment of a variety of disorders, e.g., dysphagia, achalasia, gastroesophageal reflux disease (GERD) and non-cardiac chest pain. Although, at first glance, functions of the esophagus are relatively simple, their neuronal control is considerably complex. Vagal motor neurons of the nucleus ambiguus and preganglionic neurons of the dorsal motor nucleus innervate striated and smooth muscle, respectively. Myenteric neurons represent the interface between the dorsal motor nucleus and smooth muscle but they are also involved in striated muscle innervation. Intraganglionic laminar endings (IGLEs) represent mechanosensory vagal afferent terminals. They also establish intricate connections with enteric neurons. Afferent information is implemented by the swallowing central pattern generator in the brainstem, which generates and coordinates deglutitive activity in both striated and smooth esophageal muscle and orchestrates esophageal sphincters as well as gastric adaptive relaxation. Disturbed excitation/inhibition balance in the lower esophageal sphincter results in motility disorders, e.g., achalasia and GERD. Loss of mechanosensory afferents disrupts adaptation of deglutitive motor programs to bolus variables, eventually leading to megaesophagus. Both spinal and vagal afferents appear to contribute to painful sensations, e.g., non-cardiac chest pain. Extrinsic and intrinsic neurons may be involved in intramural reflexes using acetylcholine, nitric oxide, substance P, CGRP and glutamate as main transmitters. In addition, other molecules, e.g., ATP, GABA and probably also inflammatory cytokines, may modulate these neuronal functions.

  11. Arterial innervation in development and disease.

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    Eichmann, Anne; Brunet, Isabelle

    2014-09-03

    Innervation of arteries by sympathetic nerves is well known to control blood supply to organs. Recent studies have elucidated the mechanisms that regulate the development of arterial innervation and show that in addition to vascular tone, sympathetic nerves may also influence arterial maturation and growth. Understanding sympathetic arterial innervation may lead to new approaches to treat peripheral arterial disease and hypertension. Copyright © 2014, American Association for the Advancement of Science.

  12. Is it time for cardiac innervation imaging?

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    Knuuti, J. [Turku Univ., Turku (Finland) Turku PET Center; Sipola, P. [Kuopio Univ., Kuopio (Finland)

    2005-03-01

    The autonomic nervous system plays an important role in the regulation of cardiac function and the regional distribution of cardiac nerve terminals can be visualized using scintigraphic techniques. The most commonly used tracer is iodine-123-metaiodobenzylguanidine (MIBG) but C-11-hydroxyephedrine has also been used with PET. When imaging with MIBG, the ratio of heart-to-mediastinal counts is used as an index of tracer uptake, and regional distribution is also assessed from tomographic images. The rate of clearance of the tracer can also be measured and indicates the function of the adrenergic system. Innervation imaging has been applied in patients with susceptibility to arrythmias, coronary artery disease, hypertrophic and dilated cardiomyopathy and anthracycline induced cardiotoxicity. Abnormal adrenergic innervation or function appear to exist in many pathophysiological conditions indicating that sympathetic neurons are very susceptible to damage. Abnormal findings in innervation imaging also appear to have significant prognostic value especially in patients with cardiomyopathy. Recently, it has also been shown that innervation imaging can monitor drug-induced changes in cardiac adrenergic activity. Although innervation imaging holds great promise for clinical use, the method has not received wider clinical acceptance. Larger randomized studies are required to confirm the value of innervation imaging in various specific indications.

  13. Adrenergic innervation of the rat hypothalamus

    NARCIS (Netherlands)

    Palkovits, M.; Mezey, E.; Záborszky, L.; Feminger, A.; Versteeg, D.H.G.; Wijnen, H.J.L.M.; Jong, Wybren de; Fekete, M.I.K.; Herman, J.P.; Kanyicska, B.

    The adrenergic innervation of the hypothalamus was studied by measuring hypothalamic adrenaline levels following surgical transection of the lower brain stem or electrolytic lesion of the medullary adrenaline-containing cell groups. The adrenaline levels in some hypothalamic nuclei and in the median

  14. Preganglionic innervation of the pancreas islet cells in the rat

    NARCIS (Netherlands)

    LUITEN, PGM; TERHORST, GJ; KOOPMANS, SJ; RIETBERG, M; STEFFENS, AB

    1984-01-01

    The position and number of preganglionic somata innervating the insulin-secreting β-cells of the endocrine pancreas were investigated in Wistar rats. This question was approached by comparing the innervation of the pancreas of normal rats with the innervation of the pancreas in alloxan-induced

  15. Anatomy of psoas muscle innervation: Cadaveric study.

    Science.gov (United States)

    Mahan, Mark A; Sanders, Luke E; Guan, Jian; Dailey, Andrew T; Taylor, William; Morton, David A

    2017-05-01

    Hip flexion weakness is relatively common after lateral transpsoas surgery. Persistent weakness may result from injury to the innervation of the psoas major muscles (PMMs); however, anatomical texts have conflicting descriptions of this innervation, and the branching pattern of the nerves within the psoas major, particularly relative to vertebral anatomy, has not been described. The authors dissected human cadavers to describe the branching pattern of nerves supplying the PMMs. Sixteen embalmed cadavers were dissected, and the fine branching pattern of the innervation to the PMM was studied in 24 specimens. The number of branches and width and length of each branch of nerves to the PMMs were quantified. Nerve branches innervating the PMMs arose from spinal nerve levels L1-L4, with an average of 6.3 ± 1.1 branches per muscle. The L1 nerve branch was the least consistently present, whereas L2 and L3 branches were the most robust, the most numerous, and always present. The nerve branches to the psoas major commonly crossed the intervertebral (IV) disc obliquely prior to ramification within the muscle; 76%, 80%, and 40% of specimens had a branch to the PMM cross the midportion of the L2-3, L3-4, and L4-5 IV discs, respectively. The PMMs are segmentally innervated from the L2-L4 ventral rami branches, where these branches course obliquely across the L2-3, L3-4, and L4-5 IV discs. Knowledge of the mapping of nerve branches to the PMMs may reduce injury and the incidence of persistent weak hip flexion during lateral transpsoas surgery. Clin. Anat. 30:479-486, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Catecholaminergic and serotoninergic fibres innervate the ventricular system of the hedgehog CNS.

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    Michaloudi, H C; Papadopoulos, G C

    1996-01-01

    Immunocytochemistry with antisera against serotonin (5-HT), dopamine (DA) and noradrenaline (NA) was used to detect monoaminergic (MA) fibres in the ventricular system of the hedgehog Erinaceus europaeus. Light microscopic examination of immunocytochemically stained sections revealed that the ventricular system of the hedgehog is unique among mammals in that the choroid plexuses receive CA axons and that the supraependyma and subependyma of the cerebral ventricles and the spinal central canal are innervated both by serotoninergic and catecholaminergic (CA) fibres. Supraependymal 5-HT axons were generally more abundant and created at places a large number of interconnected basket-like structures, whereas CA fibres were usually directed towards the ventricular lumen. In the lateral ventricles, CA fibres were more numerous in the ependyma lining grey matter, whereas a higher 5-HT innervation density was observed in the area between the corpus callosum and the caudate nucleus or the septum. In the 3rd ventricle, the ependyma of its dorsal part exhibited a higher 5-HT and NA innervation density, whereas DA fibres were preferentially distributed in the ventral half of the basal region. The ependyma lining the cerebral aqueduct displayed a higher MA innervation density in its ventral part. The ependymal wall of the 4th ventricle exhibited an extremely dense 5-HT innervation, mainly in the floor of the ventricle, relatively fewer NA fibres and only sparse DA ones. Few NA and relatively more 5-HT fibres were detected in the ependyma of the central canal. Finally, the circumventricular organs were unevenly innervated by the 3 types of MA fibres. The extensive monoaminergic innervation of the hedgehog ventricular system described here probably reflects a transitory evolutionary stage in the phylogeny of the MA systems with presently unknown functional implications. Images Fig. 1 Fig. 2 Figs 3-8 Figs 9-14 Figs 15-20 PMID:8886949

  17. [Microscopic innervation of the spermatic ducts and testis. I. Vas deferens].

    Science.gov (United States)

    Suárez-Garnacho, S; Vega, J A; Alvarez Arenal, A; Pérez Casas, A; Alvarez Menéndez, J C; Hernández, L C

    1989-01-01

    The microscopic innervation of the vas deferens in the rat was studied both in light and electron microscope. The nerve fibres form perivascular, intramuscular and subepithelial plexuses. Inside the connective tissue surrounding the vas deferens both isolated nerve fibres and sensory corpuscles (glomerular and Ruffine-like types) were observed. The varicosities and endings of nerve fibres contain synaptic vesicles of different sizes and electron characteristics. These varicosities were closely related to the smooth muscle cells and some of them lacked of Schwannian sheath. The nervous fibres were not in direct contact with the epithelial cells.

  18. Innervation and immunohistochemical characteristics of epididymis in Alpaca camelid (Vicugna pacos

    Directory of Open Access Journals (Sweden)

    Giovanna Liguori

    2013-03-01

    Full Text Available Alpacas (Vicugna pacos are domesticated camelids indigenous to south America and recently also bred in Europe and Italy for their high quality wool. There is little data available regarding the innervation of the male reproductive tract of this species. In the present study, the distribution of protein gene product 9.5 (PGP 9.5, neuropeptide Y (NPY, tyrosine hydroxilase (TH, calcitonin gene related peptide (CGRP and substance P (SP was analyzed in the epididymis by using immunohistochemical methods. Specimens of the caput, corpus and cauda epididymis were fixed in Bouin’s fluid and processed for immunohistochemistry analysis with primary antibodies against PGP 9.5, NPY, TH, CGRP and SP. Immunopositivity to PGP 9.5 and TH and NPY was observed in nerve fibre bundles and in single nerve fibres contained into the peritubular connective tissue. Many TH and NPY immunopositive cells were found to innervate blood vessels. Rare CGRP and SP immunopositive nerves were observed. Several PGP 9,5 and NPY immunopositive epithelial cells were observed in the caput epididymis. The results of the present study suggest a role for the innervations in modulate reproductive functions in the alpaca epididymis.

  19. L-acetylcarnitine enhances functional muscle re-innervation.

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    Pettorossi, V E; Brunetti, O; Carobi, C; Della Torre, G; Grassi, S

    1991-01-01

    The efficacy of L-acetylcarnitine and L-carnitine treatment on motor re-innervation was analyzed by evaluating different muscular parameters describing functional muscle recovery after denervation and re-innervation. The results show that L-acetylcarnitine markedly enhances functional muscle re-innervation, which on the contrary is unaffected by L-carnitine. The medial gastrocnemius muscle was denervated by cutting the nerve at the muscle entry point. After 20 days the sectioned nerve was resutured into the medial gastrocnemius muscle, and the extent of re-innervation was monitored 45 days later. L-acetylcarnitine-treated animals show significantly higher twitch and tetanic tensions of re-innervated muscle. Furthermore the results, obtained by analysing the twitch time to peak and tetanic contraction-relaxation times, suggest that L-acetylcarnitine mostly affects the functional re-innervation of slow motor units. The possible mechanisms by which L-acetylcarnitine facilitates such motor and nerve recovery are discussed.

  20. Innervation of the Anterior Sacroiliac Joint.

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    Cox, Marcus; Ng, Garrett; Mashriqi, Faizullah; Iwanaga, Joe; Alonso, Fernando; Tubbs, Kevin; Loukas, Marios; Oskouian, Rod J; Tubbs, R Shane

    2017-11-01

    Sacroiliac joint pain can be disabling and recalcitrant to medical therapy. The innervation of this joint is poorly understood, especially its anterior aspect. Therefore, the present cadaveric study was performed to better elucidate this anatomy. Twenty-four cadaveric sides underwent dissection of the anterior sacroiliac joint, with special attention given to any branches from regional nerves to this joint. No femoral, obturator, or lumbosacral trunk branches destined to the anterior sacroiliac joint were identified in the 24 sides. In 20 sides, one or two small branches (less than 0.5 mm in diameter) were found to arise from the L4 ventral ramus (10%), the L5 ventral ramus (80%), or simultaneously from both the L4 and L5 ventral rami (10%). The length of the branches ranged from 5 to 31 mm (mean, 14 mm). All these branches arose from the posterior part of the nerves and traveled to the anterior surface of the sacroiliac joint. No statistical significance was found between sides or sexes. An improved knowledge of the innervation of the anterior sacroiliac joint might decrease suffering in patients with chronic sacroiliac joint pain. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Cholinergic innervation of human mesenteric lymphatic vessels.

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    D'Andrea, V; Bianchi, E; Taurone, S; Mignini, F; Cavallotti, C; Artico, M

    2013-11-01

    The cholinergic neurotransmission within the human mesenteric lymphatic vessels has been poorly studied. Therefore, our aim is to analyse the cholinergic nerve fibres of lymphatic vessels using the traditional enzymatic techniques of staining, plus the biochemical modifications of acetylcholinesterase (AChE) activity. Specimens obtained from human mesenteric lymphatic vessels were subjected to the following experimental procedures: 1) drawing, cutting and staining of tissues; 2) staining of total nerve fibres; 3) enzymatic staining of cholinergic nerve fibres; 4) homogenisation of tissues; 5) biochemical amount of proteins; 6) biochemical amount of AChE activity; 6) quantitative analysis of images; 7) statistical analysis of data. The mesenteric lymphatic vessels show many AChE positive nerve fibres around their wall with an almost plexiform distribution. The incubation time was performed at 1 h (partial activity) and 6 h (total activity). Moreover, biochemical dosage of the same enzymatic activity confirms the results obtained with morphological methods. The homogenates of the studied tissues contain strong AChE activity. In our study, the lymphatic vessels appeared to contain few cholinergic nerve fibres. Therefore, it is expected that perivascular nerve stimulation stimulates cholinergic nerves innervating the mesenteric arteries to release the neurotransmitter AChE, which activates muscarinic or nicotinic receptors to modulate adrenergic neurotransmission. These results strongly suggest, that perivascular cholinergic nerves have little or no effect on the adrenergic nerve function in mesenteric arteries. The cholinergic nerves innervating mesenteric arteries do not mediate direct vascular responses.

  2. Innervation of the renal proximal convoluted tubule of the rat

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    Barajas, L.; Powers, K.

    1989-01-01

    Experimental data suggest the proximal tubule as a major site of neurogenic influence on tubular function. The functional and anatomical axial heterogeneity of the proximal tubule prompted this study of the distribution of innervation sites along the early, mid, and late proximal convoluted tubule (PCT) of the rat. Serial section autoradiograms, with tritiated norepinephrine serving as a marker for monoaminergic nerves, were used in this study. Freehand clay models and graphic reconstructions of proximal tubules permitted a rough estimation of the location of the innervation sites along the PCT. In the subcapsular nephrons, the early PCT (first third) was devoid of innervation sites with most of the innervation occurring in the mid (middle third) and in the late (last third) PCT. Innervation sites were found in the early PCT in nephrons located deeper in the cortex. In juxtamedullary nephrons, innervation sites could be observed on the PCT as it left the glomerulus. This gradient of PCT innervation can be explained by the different tubulovascular relationships of nephrons at different levels of the cortex. The absence of innervation sites in the early PCT of subcapsular nephrons suggests that any influence of the renal nerves on the early PCT might be due to an effect of neurotransmitter released from renal nerves reaching the early PCT via the interstitium and/or capillaries

  3. Dual Innervation of Neonatal Merkel Cells in Mouse Touch Domes

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    Luo, Wenqin

    2014-01-01

    Merkel cell-neurite complexes are specialized mechanosensory end organs that mediate discriminative touch sensation. It is well established that type I slowly adapting (SAI) mechanoreceptors, which express neural filament heavy chain (NFH), innervate Merkel cells. It was previously shown that neurotrophic factor NT3 and its receptor TrkC play crucial roles in controlling touch dome Merkel cell innervation of NFH+ fibers. In addition, nerve fibers expressing another neurotrophic tyrosine receptor kinase (NTRK), Ret, innervate touch dome Merkel cells as well. However, the relationship between afferents responsive to NT3/TrkC signaling and those expressing Ret is unclear. It is also controversial if these Ret+ fibers belong to the early or late Ret+ DRG neurons, which are defined based on the co-expression and developmental dependence of TrkA. To address these questions, we genetically traced Ret+ and TrkC+ fibers and analyzed their developmental dependence on TrkA. We found that Merkel cells in neonatal mouse touch domes receive innervation of two types of fibers: one group is Ret+, while the other subset expresses TrkC and NFH. In addition, Ret+ fibers depend on TrkA for their survival and normal innervation whereas NFH+ Merkel cell innervating fibers are almost unaltered in TrkA mutant mice, supporting that Ret+ and NFH+/TrkC+ afferents are two distinct groups. Ret signaling, on the other hand, plays a minor role for the innervation of neonatal touch domes. In contrast, Merkel cells in the glabrous skin are mainly contacted by NFH+/TrkC+ afferents. Taken together, our results suggest that neonatal Merkel cells around hair follicles receive dual innervation while Merkel cells in the glabrous skin are mainly innervated by only SAI mechanoreceptors. In addition, our results suggest that neonatal Ret+ Merkel cell innervating fibers most likely belong to the late but not early Ret+ DRG neurons. PMID:24637732

  4. Innervation of the sheep pineal gland by nonsympathetic nerve fibers containing NADPH-diaphorase activity

    DEFF Research Database (Denmark)

    López-Figueroa, Manuel O.; Ravault, Jean-Paul; Cozzi, Bruno

    1997-01-01

    Neuroanatomy, NADPH-diaphorase, nitric oxide, innervation, superior cervical ganglionectomy, neuropeptide Y.......Neuroanatomy, NADPH-diaphorase, nitric oxide, innervation, superior cervical ganglionectomy, neuropeptide Y....

  5. Innervated boomerang flap for finger pulp reconstruction.

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    Chen, Shao-Liang; Chiou, Tai-Fung

    2007-11-01

    The boomerang flap originates from the dorsolateral aspect of the proximal phalanx of an adjacent digit and is supplied by the retrograde blood flow through the vascular arcades between the dorsal and palmar digital arteries. To provide sensation of the boomerang flap for finger pulp reconstruction, the dorsal sensory branch of the proper digital nerve and the superficial sensory branch of the corresponding radial or ulnar nerve are included within the skin flap. After transfer of the flap to the injured site, epineural neurorrhaphies are done between the digital nerves of the pulp and the sensory branches of the flap. We used this sensory flap in five patients, with more than 1 year follow-up, and all patients achieved measurable two-points discrimination. The boomerang flap not only preserves the proper palmar digital artery but also provides an extended and innervated skin paddle. It seems to be an alternative choice for one-stage reconstruction of major pulp defect.

  6. Afferent innervation of the utricular macula in pigeons

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    Si, Xiaohong; Zakir, Mridha Md; Dickman, J. David

    2003-01-01

    Biotinylated dextran amine (BDA) was used to retrogradely label afferents innervating the utricular macula in adult pigeons. The pigeon utriclar macula consists of a large rectangular-shaped neuroepithelium with a dorsally curved anterior edge and an extended medioposterior tail. The macula could be demarcated into several regions based on cytoarchitectural differences. The striola occupied 30% of the macula and contained a large density of type I hair cells with fewer type II hair cells. Medial and lateral extrastriola zones were located outside the striola and contained only type II hair cells. A six- to eight-cell-wide band of type II hair cells existed near the center of the striola. The reversal line marked by the morphological polarization of hair cells coursed throughout the epithelium, near the peripheral margin, and through the center of the type II band. Calyx afferents innervated type I hair cells with calyceal terminals that contained between 2 and 15 receptor cells. Calyx afferents were located only in the striola region, exclusive of the type II band, had small total fiber innervation areas and low innervation densities. Dimorph afferents innervated both type I and type II hair cells with calyceal and bouton terminals and were primarily located in the striola region. Dimorph afferents had smaller calyceal terminals with few type I hair cells, extended fiber branches with bouton terminals and larger innervation areas. Bouton afferents innervated only type II hair cells in the extrastriola and type II band regions. Bouton afferents innervating the type II band had smaller terminal fields with fewer bouton terminals and smaller innervation areas than fibers located in the extrastriolar zones. Bouton afferents had the most bouton terminals on the longest fibers, the largest innervation areas with the highest innervation densities of all afferents. Among all afferents, smaller terminal innervation fields were observed in the striola and large fields were

  7. Innervation of the thick ascending limb of Henle

    International Nuclear Information System (INIS)

    Barajas, L.; Powers, K.V.

    1988-01-01

    The overlap of accumulations of autoradiographic grains (AAGs) on profiles of the thick ascending limb of Henle (TALH) was measured in autoradiograms of sections from rat kidneys with monoaminergic nerves labeled by means of tritiated norepinephrine. The amount of AAG overlap was used as an indirect means of quantifying innervation along the TALHs of superficial, mid-cortical, and juxtamedullary nephrons. The density of innervation along the TALH showed nephron heterogeneity; the juxtamedullary nephrons with a high pre- and postjuxtaglomerular apparatus (JGA) TALH density of innervation and the upper and midcortical nephrons with high TALH innervation densities at the level of the JGA. The pre-JGA TALH of the juxtamedullary nephrons had a significantly higher (P less than 0.001) density of innervation than the midcortical or superficial nephrons. The TALHs of juxtamedullary nephrons were found to have substantially more innervation than the TALHs of the other nephrons. For all three populations of nephrons, the pre-JGA TALH had the greatest amount of innervation. Neural regulation of TALH function would occur mainly along the pre-JGA and level of the JGA TALH. This regulation would increase TALH NaCl reabsorption (decrease luminal NaCl concentration) and therefore influence 1) the urinary concentrating mechanism, and 2) renin secretion via the macula densa mechanism. The innervation of the TALH was predominantly associated with the vasculature of the TALH's own nephron. However, innervation associated with medullary ray capillary beds from deeper nephrons was observed on pre-JGA TALHs from superficial and midcortical nephrons

  8. Innervation of the thick ascending limb of Henle

    Energy Technology Data Exchange (ETDEWEB)

    Barajas, L.; Powers, K.V.

    1988-08-01

    The overlap of accumulations of autoradiographic grains (AAGs) on profiles of the thick ascending limb of Henle (TALH) was measured in autoradiograms of sections from rat kidneys with monoaminergic nerves labeled by means of tritiated norepinephrine. The amount of AAG overlap was used as an indirect means of quantifying innervation along the TALHs of superficial, mid-cortical, and juxtamedullary nephrons. The density of innervation along the TALH showed nephron heterogeneity; the juxtamedullary nephrons with a high pre- and postjuxtaglomerular apparatus (JGA) TALH density of innervation and the upper and midcortical nephrons with high TALH innervation densities at the level of the JGA. The pre-JGA TALH of the juxtamedullary nephrons had a significantly higher (P less than 0.001) density of innervation than the midcortical or superficial nephrons. The TALHs of juxtamedullary nephrons were found to have substantially more innervation than the TALHs of the other nephrons. For all three populations of nephrons, the pre-JGA TALH had the greatest amount of innervation. Neural regulation of TALH function would occur mainly along the pre-JGA and level of the JGA TALH. This regulation would increase TALH NaCl reabsorption (decrease luminal NaCl concentration) and therefore influence 1) the urinary concentrating mechanism, and 2) renin secretion via the macula densa mechanism. The innervation of the TALH was predominantly associated with the vasculature of the TALH's own nephron. However, innervation associated with medullary ray capillary beds from deeper nephrons was observed on pre-JGA TALHs from superficial and midcortical nephrons.

  9. Catecholamine innervation of the caudal spinal cord in the rat

    DEFF Research Database (Denmark)

    Schrøder, H D; Skagerberg, G

    1985-01-01

    matter were found to contain catecholamines. In the dorsal horn the most intense fluorescence was seen in the superficial layers. The motoneuron neuropil exhibited the most prominent catecholamine-fluorescence of the ventral horn layers. In the sixth lumbar segment, which contains the motor nuclei....... In the intermediate gray the intermediolateral nucleus in thoracic and upper lumbar segments was the most heavily innervated area, followed by the medial lumbar sympathetic group, which contains the majority of the sympathetic preganglionic neurons innervating the pelvic organs. The parasympathetic intermediolateral...... nucleus in the upper sacral segments received a catecholamine innervation of moderate density. The catecholamine innervation pattern is discussed in relation to the patterns of other putative transmitters. The distribution of catecholamine fluorescence in relation to nuclei that control the pelvic organs...

  10. Cholinergic innervation of the zebrafish olfactory bulb.

    Science.gov (United States)

    Edwards, Jeffrey G; Greig, Ann; Sakata, Yoko; Elkin, Dimitry; Michel, William C

    2007-10-20

    A number of fish species receive forebrain cholinergic input but two recent reports failed to find evidence of cholinergic cell bodies or fibers in the olfactory bulbs (OBs) of zebrafish. In the current study we sought to confirm these findings by examining the OBs of adult zebrafish for choline acetyltransferase (ChAT) immunoreactivity. We observed a diffuse network of varicose ChAT-positive fibers associated with the nervus terminalis ganglion innervating the mitral cell/glomerular layer (MC/GL). The highest density of these fibers occurred in the anterior region of the bulb. The cellular targets of this cholinergic input were identified by exposing isolated OBs to acetylcholine receptor (AChR) agonists in the presence of agmatine (AGB), a cationic probe that permeates some active ion channels. Nicotine (50 microM) significantly increased the activity-dependent labeling of mitral cells and juxtaglomerular cells but not of tyrosine hydroxlase-positive dopaminergic neurons (TH(+) cells) compared to control preparations. The nAChR antagonist mecamylamine, an alpha7-nAChR subunit-specific antagonist, calcium-free artificial cerebrospinal fluid, or a cocktail of ionotropic glutamate receptor (iGluR) antagonists each blocked nicotine-stimulated labeling, suggesting that AGB does not enter the labeled neurons through activated nAChRs but rather through activated iGluRs following ACh-stimulated glutamate release. Deafferentation of OBs did not eliminate nicotine-stimulated labeling, suggesting that cholinergic input is primarily acting on bulbar neurons. These findings confirm the presence of a functioning cholinergic system in the zebrafish OB.

  11. Role of the epithelial cell rests of Malassez in the development, maintenance and regeneration of periodontal ligament tissues.

    Science.gov (United States)

    Xiong, Jimin; Gronthos, Stan; Bartold, P Mark

    2013-10-01

    Periodontitis is a highly prevalent inflammatory disease that results in damage to the tooth-supporting tissues, potentially leading to tooth loss. Periodontal tissue regeneration is a complex process that involves the collaboration of two hard tissues (cementum and alveolar bone) and two soft tissues (gingiva and periodontal ligament). To date, no periodontal-regenerative procedures provide predictable clinical outcomes. To understand the rational basis of regenerative procedures, a better understanding of the events associated with the formation of periodontal components will help to establish reliable strategies for clinical practice. An important aspect of this is the role of the Hertwig's epithelial root sheath in periodontal development and that of its descendants, the epithelial cell rests of Malassez, in the maintenance of the periodontium. An important structure during tooth root development, the Hertwig's epithelial root sheath is not only a barrier between the dental follicle and dental papilla cells but is also involved in determining the shape, size and number of roots and in the development of dentin and cementum, and may act as a source of mesenchymal progenitor cells for cementoblasts. In adulthood, the epithelial cell rests of Malassez are the only odontogenic epithelial population in the periodontal ligament. Although there is no general agreement on the functions of the epithelial cell rests of Malassez, accumulating evidence suggests that the putative roles of the epithelial cell rests of Malassez in adult periodontal ligament include maintaining periodontal ligament homeostasis to prevent ankylosis and maintain periodontal ligament space, to prevent root resorption, to serve as a target during periodontal ligament innervation and to contribute to cementum repair. Recently, ovine epithelial cell rests of Malassez cells have been shown to harbor clonogenic epithelial stem-cell populations that demonstrate similar properties to mesenchymal stromal

  12. Successful Implantation of Bioengineered, Intrinsically Innervated, Human Internal Anal Sphincter

    Science.gov (United States)

    Raghavan, Shreya; Gilmont, Robert R.; Miyasaka, Eiichi A.; Somara, Sita; Srinivasan, Shanthi; Teitelbaum, Daniel H; Bitar, Khalil N.

    2011-01-01

    Background & Aims To restore fecal continence, the weakened pressure of the internal anal sphincter (IAS) must be increased. We bioengineered intrinsically innervated human IAS, to emulate sphincteric physiology, in vitro. Methods We co-cultured human IAS circular smooth muscle with immortomouse fetal enteric neurons. We investigated the ability of bioengineered innervated human IAS, implanted in RAG1−/− mice, to undergo neovascularization and preserve the physiology of the constituent myogenic and neuronal components. Results The implanted IAS was neovascularized in vivo; numerous blood vessels were observed with no signs of inflammation or infection. Real-time force acquisition from implanted and pre-implant IAS showed distinct characteristics of IAS physiology. Features included the development of spontaneous myogenic basal tone; relaxation of 100% of basal tone in response to inhibitory neurotransmitter vasoactive intestinal peptide (VIP) and direct electrical field stimulation of the intrinsic innervation; inhibition of nitrergic and VIPergic EFS-induced relaxation (by antagonizing nitric oxide synthesis or receptor interaction); contraction in response to cholinergic stimulation with acetylcholine; and intact electromechanical coupling (evidenced by direct response to potassium chloride). Implanted, intrinsically innervated bioengineered human IAS tissue preserved the integrity and physiology of myogenic and neuronal components. Conclusion Intrinsically innervated human IAS bioengineered tissue can be successfully implanted in mice. This approach might be used to treat patients with fecal incontinence. PMID:21463628

  13. Potential Role of Semaphorin 3A and Its Receptors in Regulating Aberrant Sympathetic Innervation in Peritoneal and Deep Infiltrating Endometriosis.

    Science.gov (United States)

    Liang, Yanchun; Wang, Wei; Huang, Jiaming; Tan, Hao; Liu, Tianyu; Shang, Chunliang; Liu, Duo; Guo, Luyan; Yao, Shuzhong

    2015-01-01

    Previous studies have demonstrated the involvement of nerve repellent factors in regulation of the imbalanced innervation of endometriosis. This prospective study aims to explore the role of Sema 3A in regulating aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis. Ectopic endometriotic lesion were collected from patients with peritoneal endometriosis (n = 24) and deep infiltrating endometriosis of uterosacral ligament (n = 20) undergoing surgery for endometriosis. Eutopic endometrial samples were collected from patients with endometriosis (n = 22) or without endometriosis (n = 26). Healthy peritoneum (n = 13) from the lateral pelvic wall and healthy uterosacral ligament (n = 13) were obtained from patients who had no surgical and histological proof of endometriosis during hysterectomy for uterine fibroids. Firstly, we studied the immunostaining of Sema 3A, Plexin A1 and NRP-1 in all the tissues described above. Then we studied the nerve fiber density (NFD) of endometriosis-associated (sympathetic) nerve and para-endometriotic (sympathetic) nerve by double immunofluorescence staining. Finally we analyzed the relationship between expression of Sema 3A in stromal cells of endometriotic lesion and the aberrant innervation of endometriosis. Semi-quantitative immunostaining demonstrated that (1) Higher immunostaining of Sema 3A were found in the eutopic endometrial glandular epithelial cells from patients with endometriosis (p = 0.041) than those without endometriosis; (2) Sema 3A immunostaining was higher in glandular epithelial cells of peritoneal endometriosis (Pendometriosis, while its expression in ectopic stormal cells in both groups were significantly lower than that from eutopic endometrium of women without endometirosis (Pendometriosis-associated sympathetic nerve of peritoneal endometriosis (pendometriosis of uterosacral ligament (pperitoneal and deep infiltrating endometriosis.

  14. Potential Role of Semaphorin 3A and Its Receptors in Regulating Aberrant Sympathetic Innervation in Peritoneal and Deep Infiltrating Endometriosis

    Science.gov (United States)

    Liang, Yanchun; Wang, Wei; Huang, Jiaming; Tan, Hao; Liu, Tianyu; Shang, Chunliang; Liu, Duo; Guo, Luyan; Yao, Shuzhong

    2015-01-01

    Previous studies have demonstrated the involvement of nerve repellent factors in regulation of the imbalanced innervation of endometriosis. This prospective study aims to explore the role of Sema 3A in regulating aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis. Ectopic endometriotic lesion were collected from patients with peritoneal endometriosis (n = 24) and deep infiltrating endometriosis of uterosacral ligament (n = 20) undergoing surgery for endometriosis. Eutopic endometrial samples were collected from patients with endometriosis (n = 22) or without endometriosis (n = 26). Healthy peritoneum (n = 13) from the lateral pelvic wall and healthy uterosacral ligament (n = 13) were obtained from patients who had no surgical and histological proof of endometriosis during hysterectomy for uterine fibroids. Firstly, we studied the immunostaining of Sema 3A, Plexin A1 and NRP-1 in all the tissues described above. Then we studied the nerve fiber density (NFD) of endometriosis-associated (sympathetic) nerve and para-endometriotic (sympathetic) nerve by double immunofluorescence staining. Finally we analyzed the relationship between expression of Sema 3A in stromal cells of endometriotic lesion and the aberrant innervation of endometriosis. Semi-quantitative immunostaining demonstrated that (1) Higher immunostaining of Sema 3A were found in the eutopic endometrial glandular epithelial cells from patients with endometriosis (p = 0.041) than those without endometriosis; (2) Sema 3A immunostaining was higher in glandular epithelial cells of peritoneal endometriosis (Pendometriosis, while its expression in ectopic stormal cells in both groups were significantly lower than that from eutopic endometrium of women without endometirosis (Pendometriosis-associated sympathetic nerve of peritoneal endometriosis (pendometriosis of uterosacral ligament (pendometriosis. PMID:26720585

  15. Cortical cholinergic innervation: Distribution and source in monkeys

    International Nuclear Information System (INIS)

    Struble, R.G.; Cork, L.C.; Coyle, J.T.; Lehmann, J.; Mitchell, S.J.; Price, D.L.

    1986-01-01

    In Alzheimer's disease (AD) and its late-life variant, senile dementia of the Alzheimer's type (SDAT), the predominant neurochemical abnormalities are marked decrements in the activities of ChAT and AChE, the high affinity uptake of tritium-choline, and synthesis of acetylcholine. Two studies are undertaken to delineate more clearly the variability of cortical cholinergic innervation and the contribution of the Ch system, particularly the Ch4, to this cholinergic innervation. In the first study, ChAT activity was assessed in multiple samples of neocortex from seven normal cynomolgus monkeys. In the second study, the nbM was lesioned in order to determine the contribution of the Ch system to cortical cholinergic innervation

  16. Discrete innervation of murine taste buds by peripheral taste neurons.

    Science.gov (United States)

    Zaidi, Faisal N; Whitehead, Mark C

    2006-08-09

    The peripheral taste system likely maintains a specific relationship between ganglion cells that signal a particular taste quality and taste bud cells responsive to that quality. We have explored a measure of the receptoneural relationship in the mouse. By injecting single fungiform taste buds with lipophilic retrograde neuroanatomical markers, the number of labeled geniculate ganglion cells innervating single buds on the tongue were identified. We found that three to five ganglion cells innervate a single bud. Injecting neighboring buds with different color markers showed that the buds are primarily innervated by separate populations of geniculate cells (i.e., multiply labeled ganglion cells are rare). In other words, each taste bud is innervated by a population of neurons that only connects with that bud. Palate bud injections revealed a similar, relatively exclusive receptoneural relationship. Injecting buds in different regions of the tongue did not reveal a topographic representation of buds in the geniculate ganglion, despite a stereotyped patterned arrangement of fungiform buds as rows and columns on the tongue. However, ganglion cells innervating the tongue and palate were differentially concentrated in lateral and rostral regions of the ganglion, respectively. The principal finding that small groups of ganglion cells send sensory fibers that converge selectively on a single bud is a new-found measure of specific matching between the two principal cellular elements of the mouse peripheral taste system. Repetition of the experiments in the hamster showed a more divergent innervation of buds in this species. The results indicate that whatever taste quality is signaled by a murine geniculate ganglion neuron, that signal reflects the activity of cells in a single taste bud.

  17. The human thoracic duct is functionally innervated by adrenergic nerves

    DEFF Research Database (Denmark)

    Telinius, Niklas; Baandrup, Ulrik; Rumessen, Jüri Johs.

    2013-01-01

    ) that is predominantly adrenergic. TDs harvested from 51 patients undergoing esophageal and cardia cancer surgery were either fixed for structural investigations or maintained in vitro for the functional assessment of innervation by isometric force measurements and electrical field stimulation (EFS). Electron microscopy......, and methacholine was demonstrated by exogenous application to human TD ring segments. Norepinephrine provided the most consistent responses, whereas responses to the other agonists varied. We conclude that the human TD is functionally innervated with both cholinergic and adrenergic components, with the latter...

  18. Regulation of Epithelial Sodium Transport via Epithelial Na+ Channel

    Science.gov (United States)

    Marunaka, Yoshinori; Niisato, Naomi; Taruno, Akiyuki; Ohta, Mariko; Miyazaki, Hiroaki; Hosogi, Shigekuni; Nakajima, Ken-ichi; Kusuzaki, Katsuyuki; Ashihara, Eishi; Nishio, Kyosuke; Iwasaki, Yoshinobu; Nakahari, Takashi; Kubota, Takahiro

    2011-01-01

    Renal epithelial Na+ transport plays an important role in homeostasis of our body fluid content and blood pressure. Further, the Na+ transport in alveolar epithelial cells essentially controls the amount of alveolar fluid that should be kept at an appropriate level for normal gas exchange. The epithelial Na+ transport is generally mediated through two steps: (1) the entry step of Na+ via epithelial Na+ channel (ENaC) at the apical membrane and (2) the extrusion step of Na+ via the Na+, K+-ATPase at the basolateral membrane. In general, the Na+ entry via ENaC is the rate-limiting step. Therefore, the regulation of ENaC plays an essential role in control of blood pressure and normal gas exchange. In this paper, we discuss two major factors in ENaC regulation: (1) activity of individual ENaC and (2) number of ENaC located at the apical membrane. PMID:22028593

  19. Development of the intrinsic and extrinsic innervation of the gut.

    Science.gov (United States)

    Uesaka, Toshihiro; Young, Heather M; Pachnis, Vassilis; Enomoto, Hideki

    2016-09-15

    The gastrointestinal (GI) tract is innervated by intrinsic enteric neurons and by extrinsic efferent and afferent nerves. The enteric (intrinsic) nervous system (ENS) in most regions of the gut consists of two main ganglionated layers; myenteric and submucosal ganglia, containing numerous types of enteric neurons and glial cells. Axons arising from the ENS and from extrinsic neurons innervate most layers of the gut wall and regulate many gut functions. The majority of ENS cells are derived from vagal neural crest cells (NCCs), which proliferate, colonize the entire gut, and first populate the myenteric region. After gut colonization by vagal NCCs, the extrinsic nerve fibers reach the GI tract, and Schwann cell precursors (SCPs) enter the gut along the extrinsic nerves. Furthermore, a subpopulation of cells in myenteric ganglia undergoes a radial (inward) migration to form the submucosal plexus, and the intrinsic and extrinsic innervation to the mucosal region develops. Here, we focus on recent progress in understanding the developmental processes that occur after the gut is colonized by vagal ENS precursors, and provide an up-to-date overview of molecular mechanisms regulating the development of the intrinsic and extrinsic innervation of the GI tract. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Testosterone supplementation restores vasopressin innervation in the senescent rat brain

    NARCIS (Netherlands)

    Goudsmit, E.; Fliers, E.; Swaab, D. F.

    1988-01-01

    The vasopressin (AVP) innervation in the male rat brain is decreased in senescence. This decrease is particularly pronounced in brain regions where AVP fiber density is dependent on plasma levels of sex steroids. Since plasma testosterone levels decrease progressively with age in the rat, the

  1. Autonomic innervation of the heart. Role of molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Slart, Riemer H.J.A; Elsinga, Philip H. [Univ. Medical Center Groningen (Netherlands). Nuclear Medicine and Molecular Imaging; Tio, Rene A. [Univ. Medical Center Groningen (Netherlands). Thorax Center Cardiology; Schwaiger, Markus (ed.) [Technische Univ. Muenchen Klinikum Rechts der Isar (Germany). Nuklearmedizinische Klinik

    2015-03-01

    Reviews in detail the value of SPECT-CT and PET-CT in the imaging of cardiac innervation. Details the role of imaging in a range of conditions and diseases. Includes important background on pathophysiology, tracers, radiopharmaceutical production, and kinetic modeling software. This book explains in detail the potential value of the hybrid modalities, SPECT-CT and PET-CT, in the imaging of cardiac innervation in a wide range of conditions and diseases, including ischemic heart disease, diabetes mellitus, heart failure, amyloidosis, heart transplantation, and ventricular arrhythmias. Imaging of the brain-heart axis in neurodegenerative disease and stress and of cardiotoxicity is also discussed. The roles of the various available tracers are fully considered, and individual chapters address radiopharmaceutical development under GMP, imaging physics, and kinetic modeling software. Highly relevant background information is included on the autonomic nervous system of the heart and its pathophysiology, and in addition future perspectives are discussed. Awareness of the importance of autonomic innervation of the heart for the optimal management of cardiac patients is growing, and there is an evident need for objective measurement techniques or imaging modalities. In this context, Autonomic Innervation of the Heart will be of wide interest to clinicians, researchers, and industry.

  2. Autonomic innervation of the heart. Role of molecular imaging

    International Nuclear Information System (INIS)

    Slart, Riemer H.J.A; Elsinga, Philip H.; Tio, Rene A.; Schwaiger, Markus

    2015-01-01

    Reviews in detail the value of SPECT-CT and PET-CT in the imaging of cardiac innervation. Details the role of imaging in a range of conditions and diseases. Includes important background on pathophysiology, tracers, radiopharmaceutical production, and kinetic modeling software. This book explains in detail the potential value of the hybrid modalities, SPECT-CT and PET-CT, in the imaging of cardiac innervation in a wide range of conditions and diseases, including ischemic heart disease, diabetes mellitus, heart failure, amyloidosis, heart transplantation, and ventricular arrhythmias. Imaging of the brain-heart axis in neurodegenerative disease and stress and of cardiotoxicity is also discussed. The roles of the various available tracers are fully considered, and individual chapters address radiopharmaceutical development under GMP, imaging physics, and kinetic modeling software. Highly relevant background information is included on the autonomic nervous system of the heart and its pathophysiology, and in addition future perspectives are discussed. Awareness of the importance of autonomic innervation of the heart for the optimal management of cardiac patients is growing, and there is an evident need for objective measurement techniques or imaging modalities. In this context, Autonomic Innervation of the Heart will be of wide interest to clinicians, researchers, and industry.

  3. Variations of six transmembrane epithelial antigen of prostate 4 (STEAP4) gene are associated with metabolic syndrome in a female Uygur general population.

    Science.gov (United States)

    Nanfang, Li; Yanying, Guo; Hongmei, Wang; Zhitao, Yan; Juhong, Zhang; Ling, Zhou; Wenli, Luo

    2010-08-01

    Metabolic syndrome (MetS) is linked with visceral obesity and is associated with a clustering of abnormalities (including impaired glucose tolerance, insulin resistance, dyslipidemia and hypertension). Six transmembrane epithelial antigen of prostate 4 (STEAP4) was associated with human obesity. STEAP4 gene represents a strong biological and positional candidate for a susceptibility factor for MetS. Uygur Chinese is a relatively isolated population with a relatively homogeneous environment and a high prevalence of MetS. We undertook this study to investigate the relationship between STEAP4 gene variations and MetS in a Uygur general population. The functional regions of STEAP4 gene were sequenced in Uygur patients with MetS. Four representative variations, rs1981529, rs34741656, rs8122 and 6031T/G (unsuccessfully genotyped), selected with a r² cutoff of 0.8 and minor allele frequency of >5%, were genotyped in 858 MetS and 687 non-MetS controls. Fourteen novel and six known single nucleotide polymorphisms (SNPs) including 2 nonsynonymous SNPs in the STEAP4 gene were identified. SNPs rs8122 and rs1981529 were significantly associated with MetS phenotype in females [additive p = 0.032 and p = 0.011; ORs (95% CI) adjusted for age 0.772 (0.625-0.954) and 0.740 (0.582-0.941), respectively]. Two common haplotypes 1 (rs8122/rs1981529/rs34741656, G-A-G) and 2 (A-G-G) had significantly higher (permutation p = 0.044) and lower (permutation p = 0.009) frequency in MetS than that in controls in females. Multiple linear regression analysis revealed a significant association of the SNPs rs8122 and rs1981529 with HDL-c level in MetS cases (p = 0.001 and 0.024) and in a combined sample (p = 0.004 and 0.009). STEAP4 genetic variations are likely to be associated with metabolic syndrome in a female Uygur general population. Copyright © 2010 IMSS. Published by Elsevier Inc. All rights reserved.

  4. Unilateral variant motor innervations of flexure muscles of arm

    Directory of Open Access Journals (Sweden)

    A S Yogesh

    2010-01-01

    Full Text Available The musculocutaneous nerve usually branches out from the lateral cord of brachial plexus. It innervates the corcobrachialis, biceps brachii and brachialis muscles and continues as the lateral cutaneous nerve of forearm without exhibiting any communication with the median nerve or any other nerve. We report unilateral variation in motor innervations of the left arm in a 58-year-old male cadaver. The musculocutaneous nerve was found to be absent. A muscular branch of the median nerve was supplying the coracobrachialis muscle. In the middle of arm, the median nerve was found to be branching out, bifurcating and supplying the long and short head of biceps. The median nerve was found to be giving a separate branch, which supplied the brachialis muscle and continued as the lateral cutaneous nerve of forearm. The right sided structures were found to be normal. Surgeons should keep such variations in mind while performing arm surgeries.

  5. The spatiotemporal development of innervation in spinal ligaments of chickens.

    OpenAIRE

    Jiang, H; Moreau, M; Greidanus, N; Bilo, J; Russell, G; Raso, J; Bagnall, K

    1996-01-01

    The development of the innervation of both central and lateral (intertransverse) spinal ligaments was investigated in chickens between the time of hatching and 13 wk of age. A total of 36 White Leghorn chickens in 4 groups of 9 at ages 0, 2, 7, and 13 wk were used. The spinal ligaments were dissected, serially sectioned and labelled with a monoclonal antibody against neurofilament protein and observed using either conventional fluorescence or confocal microscopy. Only a few nerve elements wer...

  6. Maintenance of Taste Organs Is Strictly Dependent on Epithelial Hedgehog/GLI Signaling.

    Directory of Open Access Journals (Sweden)

    Alexandre N Ermilov

    2016-11-01

    Full Text Available For homeostasis, lingual taste papilla organs require regulation of epithelial cell survival and renewal, with sustained innervation and stromal interactions. To investigate a role for Hedgehog/GLI signaling in adult taste organs we used a panel of conditional mouse models to manipulate GLI activity within epithelial cells of the fungiform and circumvallate papillae. Hedgehog signaling suppression rapidly led to taste bud loss, papilla disruption, and decreased proliferation in domains of papilla epithelium that contribute to taste cells. Hedgehog responding cells were eliminated from the epithelium but retained in the papilla stromal core. Despite papilla disruption and loss of taste buds that are a major source of Hedgehog ligand, innervation to taste papillae was maintained, and not misdirected, even after prolonged GLI blockade. Further, vimentin-positive fibroblasts remained in the papilla core. However, retained innervation and stromal cells were not sufficient to maintain taste bud cells in the context of compromised epithelial Hedgehog signaling. Importantly taste organ disruption after GLI blockade was reversible in papillae that retained some taste bud cell remnants where reactivation of Hedgehog signaling led to regeneration of papilla epithelium and taste buds. Therefore, taste bud progenitors were either retained during epithelial GLI blockade or readily repopulated during recovery, and were poised to regenerate taste buds once Hedgehog signaling was restored, with innervation and papilla connective tissue elements in place. Our data argue that Hedgehog signaling is essential for adult tongue tissue maintenance and that taste papilla epithelial cells represent the key targets for physiologic Hedgehog-dependent regulation of taste organ homeostasis. Because disruption of GLI transcriptional activity in taste papilla epithelium is sufficient to drive taste organ loss, similar to pharmacologic Hedgehog pathway inhibition, the findings

  7. Maintenance of Taste Organs Is Strictly Dependent on Epithelial Hedgehog/GLI Signaling.

    Science.gov (United States)

    Ermilov, Alexandre N; Kumari, Archana; Li, Libo; Joiner, Ariell M; Grachtchouk, Marina A; Allen, Benjamin L; Dlugosz, Andrzej A; Mistretta, Charlotte M

    2016-11-01

    For homeostasis, lingual taste papilla organs require regulation of epithelial cell survival and renewal, with sustained innervation and stromal interactions. To investigate a role for Hedgehog/GLI signaling in adult taste organs we used a panel of conditional mouse models to manipulate GLI activity within epithelial cells of the fungiform and circumvallate papillae. Hedgehog signaling suppression rapidly led to taste bud loss, papilla disruption, and decreased proliferation in domains of papilla epithelium that contribute to taste cells. Hedgehog responding cells were eliminated from the epithelium but retained in the papilla stromal core. Despite papilla disruption and loss of taste buds that are a major source of Hedgehog ligand, innervation to taste papillae was maintained, and not misdirected, even after prolonged GLI blockade. Further, vimentin-positive fibroblasts remained in the papilla core. However, retained innervation and stromal cells were not sufficient to maintain taste bud cells in the context of compromised epithelial Hedgehog signaling. Importantly taste organ disruption after GLI blockade was reversible in papillae that retained some taste bud cell remnants where reactivation of Hedgehog signaling led to regeneration of papilla epithelium and taste buds. Therefore, taste bud progenitors were either retained during epithelial GLI blockade or readily repopulated during recovery, and were poised to regenerate taste buds once Hedgehog signaling was restored, with innervation and papilla connective tissue elements in place. Our data argue that Hedgehog signaling is essential for adult tongue tissue maintenance and that taste papilla epithelial cells represent the key targets for physiologic Hedgehog-dependent regulation of taste organ homeostasis. Because disruption of GLI transcriptional activity in taste papilla epithelium is sufficient to drive taste organ loss, similar to pharmacologic Hedgehog pathway inhibition, the findings suggest that taste

  8. Postnatal reduction of BDNF regulates the developmental remodeling of taste bud innervation.

    Science.gov (United States)

    Huang, Tao; Ma, Liqun; Krimm, Robin F

    2015-09-15

    The refinement of innervation is a common developmental mechanism that serves to increase the specificity of connections following initial innervation. In the peripheral gustatory system, the extent to which innervation is refined and how refinement might be regulated is unclear. The initial innervation of taste buds is controlled by brain-derived neurotrophic factor (BDNF). Following initial innervation, taste receptor cells are added and become newly innervated. The connections between the taste receptor cells and nerve fibers are likely to be specific in order to retain peripheral coding mechanisms. Here, we explored the possibility that the down-regulation of BDNF regulates the refinement of taste bud innervation during postnatal development. An analysis of BDNF expression in Bdnf(lacZ/+) mice and real-time reverse transcription polymerase chain reaction (RT-PCR) revealed that BDNF was down-regulated between postnatal day (P) 5 and P10. This reduction in BDNF expression was due to a loss of precursor/progenitor cells that express BDNF, while the expression of BDNF in the subpopulations of taste receptor cells did not change. Gustatory innervation, which was identified by P2X3 immunohistochemistry, was lost around the perimeter where most progenitor/precursor cells are located. In addition, the density of innervation in the taste bud was reduced between P5 and P10, because taste buds increase in size without increasing innervation. This reduction of innervation density was blocked by the overexpression of BDNF in the precursor/progenitor population of taste bud cells. Together these findings indicate that the process of BDNF restriction to a subpopulation of taste receptor cells between P5 and P10, results in a refinement of gustatory innervation. We speculate that this refinement results in an increased specificity of connections between neurons and taste receptor cells during development. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Postnatal reduction of BDNF regulates the developmental remodeling of taste bud innervation

    Science.gov (United States)

    Huang, Tao; Ma, Liqun; Krimm, Robin F

    2015-01-01

    The refinement of innervation is a common developmental mechanism that serves to increase the specificity of connections following initial innervation. In the peripheral gustatory system, the extent to which innervation is refined and how refinement might be regulated is unclear. The initial innervation of taste buds is controlled by brain-derived neurotrophic factor (BDNF). Following initial innervation, taste receptor cells are added and become newly innervated. The connections between the taste receptor cells and nerve fibers are likely to be specific in order to retain peripheral coding mechanisms. Here, we explored the possibility that the down-regulation of BDNF regulates the refinement of taste bud innervation during postnatal development. An analysis of BDNF expression in BdnflacZ/+ mice and real-time reverse transcription polymerase chain reaction (RT-PCR) revealed that BDNF was down-regulated between postnatal day (P) 5 and P10. This reduction in BDNF expression was due to a loss of precursor/progenitor cells that express BDNF, while the expression of BDNF in the subpopulations of taste receptor cells did not change. Gustatory innervation, which was identified by P2X3 immunohistochemistry, was lost around the perimeter where most progenitor/precursor cells are located. In addition, the density of innervation in the taste bud was reduced between P5 and P10, because taste buds increase in size without increasing innervation. This reduction of innervation density was blocked by the overexpression of BDNF in the precursor/progenitor population of taste bud cells. Together these findings indicate that the process of BDNF restriction to a subpopulation of taste receptor cells between P5 and P10, results in a refinement of gustatory innervation. We speculate that this refinement results in an increased specificity of connections between neurons and taste receptor cells during development. PMID:26164656

  10. Egr3 dependent sympathetic target tissue innervation in the absence of neuron death.

    Directory of Open Access Journals (Sweden)

    Lin Li

    Full Text Available Nerve Growth Factor (NGF is a target tissue derived neurotrophin required for normal sympathetic neuron survival and target tissue innervation. NGF signaling regulates gene expression in sympathetic neurons, which in turn mediates critical aspects of neuron survival, axon extension and terminal axon branching during sympathetic nervous system (SNS development. Egr3 is a transcription factor regulated by NGF signaling in sympathetic neurons that is essential for normal SNS development. Germline Egr3-deficient mice have physiologic dysautonomia characterized by apoptotic sympathetic neuron death and abnormal innervation to many target tissues. The extent to which sympathetic innervation abnormalities in the absence of Egr3 is caused by altered innervation or by neuron death during development is unknown. Using Bax-deficient mice to abrogate apoptotic sympathetic neuron death in vivo, we show that Egr3 has an essential role in target tissue innervation in the absence of neuron death. Sympathetic target tissue innervation is abnormal in many target tissues in the absence of neuron death, and like NGF, Egr3 also appears to effect target tissue innervation heterogeneously. In some tissues, such as heart, spleen, bowel, kidney, pineal gland and the eye, Egr3 is essential for normal innervation, whereas in other tissues such as lung, stomach, pancreas and liver, Egr3 appears to have little role in innervation. Moreover, in salivary glands and heart, two tissues where Egr3 has an essential role in sympathetic innervation, NGF and NT-3 are expressed normally in the absence of Egr3 indicating that abnormal target tissue innervation is not due to deregulation of these neurotrophins in target tissues. Taken together, these results clearly demonstrate a role for Egr3 in mediating sympathetic target tissue innervation that is independent of neuron survival or neurotrophin deregulation.

  11. Putaminal serotonergic innervation: monitoring dyskinesia risk in Parkinson disease.

    Science.gov (United States)

    Lee, Jee-Young; Seo, Seongho; Lee, Jae Sung; Kim, Han-Joon; Kim, Yu Kyeong; Jeon, Beom S

    2015-09-08

    To explore serotonergic innervation in the basal ganglia in relation to levodopa-induced dyskinesia in patients with Parkinson disease (PD). A total of 30 patients with PD without dementia or depression were divided into 3 matched groups (dyskinetic, nondyskinetic, and drug-naive) for this study. We acquired 2 PET scans and 3T MRI for each patient using [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ((11)C-DASB) and N-(3-[(18)F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane ((18)F-FP-CIT). Then we analyzed binding potentials of the 2 radiotracers at basal ganglia structures and correlations with clinical variables. We observed no difference in (18)F-FP-CIT binding between dyskinetic and nondyskinetic patients, whereas there were differences in (11)C-DASB binding for the caudate and putamen. Binding potential ratios ((11)C-DASB/(18)F-FP-CIT) at the putamen, which indicate serotoninergic fiber innervation relative to dopaminergic fiber availability, were highest in the dyskinetic group, followed by the nondyskinetic and drug-naive PD groups. (11)C-DASB/(18)F-FP-CIT ratios at the putamen and pallidum correlated positively with Unified Parkinson's Disease Rating Scale (UPDRS) total scores and duration of PD, and pallidal binding ratio also correlated with the UPDRS motor scores. Ratios were not dependent on dopaminergic medication dosages for any of the regions studied. Relative serotonergic innervation of the putamen and pallidum increased with clinical PD progression and was highest in patients with established dyskinesia. The serotonin/dopamine transporter ratio might be a potential marker of disease progression and an indicator of risk for levodopa-induced dyskinesia in PD. A prospective evaluation is warranted in the future. © 2015 American Academy of Neurology.

  12. The sympathetic innervation of the heart: Important new insights.

    Science.gov (United States)

    Coote, J H; Chauhan, R A

    2016-08-01

    Autonomic control of the heart has a significant influence over development of life threatening arrhythmias that can lead to sudden cardiac death. Sympathetic activity is known to be upregulated during these conditions and hence the sympathetic nerves present a target for treatment. However, a better understanding of the anatomy and physiology of cardiac sympathetic nerves is required for the progression of clinical interventions. This review explores the organization of the cardiac sympathetic nerves, from the preganglionic origin to the postganglionic innervations, and provides an overview of literature surrounding anti-arrhythmic therapies including thoracic sympathectomy and dorsal spinal cord stimulation. Several features of the innervation are clear. The cardiac nerves differentially supply the nodal and myocardial tissue of the heart and are dependent on activity generated in spinal neurones in the upper thoracic cord which project to synapse with ganglion cells in the stellate complex on each side. Networks of spinal interneurones determine the pattern of activity. Groups of spinal neurones selectively target specific regions of the heart but whether they exhibit a functional selectivity has still to be elucidated. Electrical or ischemic signals can lead to remodeling of nerves in the heart or ganglia. Surgical and electrical methods are proving to be clinically beneficial in reducing atrial and ventricular arrhythmias, heart failure and severe cardiac pain. This is a rapidly developing area and we need more basic understanding of how these methods work to ensure safety and reduction of side effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Differential serotonergic innervation of the amygdala in bonobos and chimpanzees.

    Science.gov (United States)

    Stimpson, Cheryl D; Barger, Nicole; Taglialatela, Jared P; Gendron-Fitzpatrick, Annette; Hof, Patrick R; Hopkins, William D; Sherwood, Chet C

    2016-03-01

    Humans' closest living relatives are bonobos (Pan paniscus) and chimpanzees (Pan troglodytes), yet these great ape species differ considerably from each other in terms of social behavior. Bonobos are more tolerant of conspecifics in competitive contexts and often use sexual behavior to mediate social interactions. Chimpanzees more frequently employ aggression during conflicts and actively patrol territories between communities. Regulation of emotional responses is facilitated by the amygdala, which also modulates social decision-making, memory and attention. Amygdala responsiveness is further regulated by the neurotransmitter serotonin. We hypothesized that the amygdala of bonobos and chimpanzees would differ in its neuroanatomical organization and serotonergic innervation. We measured volumes of regions and the length density of serotonin transporter-containing axons in the whole amygdala and its lateral, basal, accessory basal and central nuclei. Results showed that accessory basal nucleus volume was larger in chimpanzees than in bonobos. Of particular note, the amygdala of bonobos had more than twice the density of serotonergic axons than chimpanzees, with the most pronounced differences in the basal and central nuclei. These findings suggest that variation in serotonergic innervation of the amygdala may contribute to mediating the remarkable differences in social behavior exhibited by bonobos and chimpanzees. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  14. Limited distal organelles and synaptic function in extensive monoaminergic innervation.

    Science.gov (United States)

    Tao, Juan; Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S

    2017-08-01

    Organelles such as neuropeptide-containing dense-core vesicles (DCVs) and mitochondria travel down axons to supply synaptic boutons. DCV distribution among en passant boutons in small axonal arbors is mediated by circulation with bidirectional capture. However, it is not known how organelles are distributed in extensive arbors associated with mammalian dopamine neuron vulnerability, and with volume transmission and neuromodulation by monoamines and neuropeptides. Therefore, we studied presynaptic organelle distribution in Drosophila octopamine neurons that innervate ∼20 muscles with ∼1500 boutons. Unlike in smaller arbors, distal boutons in these arbors contain fewer DCVs and mitochondria, although active zones are present. Absence of vesicle circulation is evident by proximal nascent DCV delivery, limited impact of retrograde transport and older distal DCVs. Traffic studies show that DCV axonal transport and synaptic capture are not scaled for extensive innervation, thus limiting distal delivery. Activity-induced synaptic endocytosis and synaptic neuropeptide release are also reduced distally. We propose that limits in organelle transport and synaptic capture compromise distal synapse maintenance and function in extensive axonal arbors, thereby affecting development, plasticity and vulnerability to neurodegenerative disease. © 2017. Published by The Company of Biologists Ltd.

  15. Soft Ultrathin Electronics Innervated Adaptive Fully Soft Robots.

    Science.gov (United States)

    Wang, Chengjun; Sim, Kyoseung; Chen, Jin; Kim, Hojin; Rao, Zhoulyu; Li, Yuhang; Chen, Weiqiu; Song, Jizhou; Verduzco, Rafael; Yu, Cunjiang

    2018-03-01

    Soft robots outperform the conventional hard robots on significantly enhanced safety, adaptability, and complex motions. The development of fully soft robots, especially fully from smart soft materials to mimic soft animals, is still nascent. In addition, to date, existing soft robots cannot adapt themselves to the surrounding environment, i.e., sensing and adaptive motion or response, like animals. Here, compliant ultrathin sensing and actuating electronics innervated fully soft robots that can sense the environment and perform soft bodied crawling adaptively, mimicking an inchworm, are reported. The soft robots are constructed with actuators of open-mesh shaped ultrathin deformable heaters, sensors of single-crystal Si optoelectronic photodetectors, and thermally responsive artificial muscle of carbon-black-doped liquid-crystal elastomer (LCE-CB) nanocomposite. The results demonstrate that adaptive crawling locomotion can be realized through the conjugation of sensing and actuation, where the sensors sense the environment and actuators respond correspondingly to control the locomotion autonomously through regulating the deformation of LCE-CB bimorphs and the locomotion of the robots. The strategy of innervating soft sensing and actuating electronics with artificial muscles paves the way for the development of smart autonomous soft robots. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

    Science.gov (United States)

    Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

    2016-08-19

    Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

  17. Sensory innervation of the temporomandibular joint in the mouse.

    Science.gov (United States)

    Dreessen, D; Halata, Z; Strasmann, T

    1990-01-01

    The sensory innervation of the temporomandibular joints (TMJs) of 8 STR/IN mice was investigated by means of light and electron microscopy. Through the cutting of complete semithin sections in series it was possible to investigate the joints thoroughly. Additionally, one joint with its nerve supply was reconstructed three-dimensionally with a computerized three-dimensional programme. The reconstruction was based on one complete semithin section series. The joint's nerve supply originates from the nervus auriculotemporalis and additionally from motor branches of the n. mandibularis: n. massetericus, n. pterygoideus lateralis and the nn. temporales posteriores. The greatest number of nerve fibres and endings is located in the dorsolateral part of the joint capsule. They lie only in the stratum fibrosum and subsynovially. Neither the stratum synoviale nor the discus articularis contain any nerve fibres or endings, whereas the peri-articular loose connective tissue is richly innervated. The only type of nerve ending observed within the joint was the free nerve ending, which is assumed to serve not only as a nociceptor but also as a polymodal mechanoreceptor. Merely within the insertion of the musculus pterygoideus lateralis at the collum mandibulae single stretch receptors of the Ruffini type were observed. Ultrastructurally, they correspond to those described in the cat's knee joint. Neither lamellated nor nerve endings of the Golgi or Pacini type were observed in the joint or in the peri-articular connective tissue. The unexpected paucity of nerve fibres and endings in the TMJ itself of the mouse suggests that the afferent information from the joint is less important for position sense and movement than the afferent information from muscles, tendons and periodontal ligaments.

  18. Cortical Reorganization in Dual Innervation by Single Peripheral Nerve.

    Science.gov (United States)

    Zheng, Mou-Xiong; Shen, Yun-Dong; Hua, Xu-Yun; Hou, Ao-Lin; Zhu, Yi; Xu, Wen-Dong

    2017-09-21

    Functional recovery after peripheral nerve injury and repair is related with cortical reorganization. However, the mechanism of innervating dual targets by 1 donor nerve is largely unknown. To investigate the cortical reorganization when the phrenic nerve simultaneously innervates the diaphragm and biceps. Total brachial plexus (C5-T1) injury rats were repaired by phrenic nerve-musculocutaneous nerve transfer with end-to-side (n = 15) or end-to-end (n = 15) neurorrhaphy. Brachial plexus avulsion (n = 5) and sham surgery (n = 5) rats were included for control. Behavioral observation, electromyography, and histologic studies were used for confirming peripheral nerve reinnervation. Cortical representations of the diaphragm and reinnervated biceps were studied by intracortical microstimulation techniques before and at months 0.5, 3, 5, 7, and 10 after surgery. At month 0.5 after complete brachial plexus injury, the motor representation of the injured forelimb disappeared. The diaphragm representation was preserved in the "end-to-side" group but absent in the "end-to-end" group. Rhythmic contraction of biceps appeared in "end-to-end" and "end-to-side" groups, and the biceps representation reappeared in the original biceps and diaphragm areas at months 3 and 5. At month 10, it was completely located in the original biceps area in the "end-to-end" group. Part of the biceps representation remained in the original diaphragm area in the "end-to-side" group. Destroying the contralateral motor cortex did not eliminate respiration-related contraction of biceps. The brain tends to resume biceps representation from the original diaphragm area to the original biceps area following phrenic nerve transfer. The original diaphragm area partly preserves reinnervated biceps representation after end-to-side transfer. Copyright © 2017 by the Congress of Neurological Surgeons

  19. Staphylococcus aureus alpha-toxin mediates general and cell type-specific changes in metabolite concentrations of immortalized human airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Philipp Gierok

    Full Text Available Staphylococcus aureus alpha-toxin (Hla is a potent pore-forming cytotoxin that plays an important role in the pathogenesis of S. aureus infections, including pneumonia. The impact of Hla on the dynamics of the metabolome in eukaryotic host cells has not been investigated comprehensively. Using 1H-NMR, GC-MS and HPLC-MS, we quantified the concentrations of 51 intracellular metabolites and assessed alterations in the amount of 25 extracellular metabolites in the two human bronchial epithelial cell lines S9 and 16HBE14o- under standard culture conditions and after treatment with sub-lethal amounts (2 µg/ml of recombinant Hla (rHla in a time-dependent manner. Treatment of cells with rHla caused substantial decreases in the concentrations of intracellular metabolites from different metabolic pathways in both cell lines, including ATP and amino acids. Concomitant increases in the extracellular concentrations were detected for various intracellular compounds, including nucleotides, glutathione disulfide and NAD+. Our results indicate that rHla has a major impact on the metabolome of eukaryotic cells as a consequence of direct rHla-mediated alterations in plasma membrane permeability or indirect effects mediated by cellular signalling. However, cell-specific changes also were observed. Glucose consumption and lactate production rates suggest that the glycolytic activity of S9 cells, but not of 16HBE14o- cells, is increased in response to rHla. This could contribute to the observed higher level of resistance of S9 cells against rHla-induced membrane damage.

  20. Sympathetic Innervation during Development Is Necessary for Pancreatic Islet Architecture and Functional Maturation

    Directory of Open Access Journals (Sweden)

    Philip Borden

    2013-07-01

    Full Text Available Sympathetic neurons depend on target-derived neurotrophic cues to control their survival and growth. However, whether sympathetic innervation contributes reciprocally to the development of target tissues is less clear. Here, we report that sympathetic innervation is necessary for the formation of the pancreatic islets of Langerhans and for their functional maturation. Genetic or pharmacological ablation of sympathetic innervation during development resulted in altered islet architecture, reduced insulin secretion, and impaired glucose tolerance in mice. Similar defects were observed with pharmacological blockade of β-adrenergic signaling. Conversely, the administration of a β-adrenergic agonist restored islet morphology and glucose tolerance in deinnervated animals. Furthermore, in neuron-islet cocultures, sympathetic neurons promoted islet cell migration in a β-adrenergic-dependent manner. This study reveals that islet architecture requires extrinsic inductive cues from neighboring tissues such as sympathetic nerves and suggests that early perturbations in sympathetic innervation might underlie metabolic disorders.

  1. Positron emission tomographic imaging of cardiac sympathetic innervation and function

    International Nuclear Information System (INIS)

    Goldstein, D.S.; Chang, P.C.; Eisenhofer, G.; Miletich, R.; Finn, R.; Bacher, J.; Kirk, K.L.; Bacharach, S.; Kopin, I.J.

    1990-01-01

    Sites of uptake, storage, and metabolism of [ 18 F]fluorodopamine and excretion of [ 18 F]fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of [ 18 F]-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of [ 18 F]fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function

  2. The vagal innervation of the gut and immune homeostasis.

    Science.gov (United States)

    Matteoli, Gianluca; Boeckxstaens, Guy E

    2013-08-01

    The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. Recently, in animal models of sepsis, the vagus nerve (VN) has been proposed to play a crucial role in the regulation of the immune response, also referred to as the cholinergic anti-inflammatory pathway. The VN, through release of acetylcholine, dampens immune cell activation by interacting with α-7 nicotinic acetylcholine receptors. Recent evidence suggests that the vagal innervation of the gastrointestinal tract also plays a major role controlling intestinal immune activation. Indeed, VN electrical stimulation potently reduces intestinal inflammation restoring intestinal homeostasis, whereas vagotomy has the reverse effect. In this review, we will discuss the current understanding concerning the mechanisms and effects involved in the cholinergic anti-inflammatory pathway in the gastrointestinal tract. Deeper investigation on this counter-regulatory neuroimmune mechanism will provide new insights in the cross-talk between the nervous and immune system leading to the identification of new therapeutic targets to treat intestinal immune disease.

  3. Vasoactive intestinal polypeptide (VIP) innervation of the human eyelid glands.

    Science.gov (United States)

    Seifert, P; Spitznas, M

    1999-06-01

    This study was conducted to obtain morphological proof of innervating nerve fibres in the glands of the human eyelid (accessory lacrimal glands of Wolfring, meibomian glands, goblet cells, glands of Zeis, glands of Moll, sweat glands, glands of lanugo hair follicles) and identification of the secretomotorically active neuropeptide vasoactive intestinal polypeptide (VIP) as a common transmitter. Epoxy-embedded ultrathin sections of tissue samples from human eyelids were studied using electron microscopy. Paraffin sections fixed in Bouin-Hollande solution were immunostained with rabbit antiserum against VIP. With the electron microscope we were able to identify nerves in the glandular stroma of all the glands examined with the exception of goblet cells. Intraepithelial single axons were only seen in the parenchyma of Wolfring glands. The morphological findings corresponded with the immunological finding of VIP-positive, nerve-like structures in the same locations, with the exception of lanugo hair follicle glands, and goblet cells. Our findings indicate that the glands of the eyelids and main lacrimal gland represent a functional unit with VIP as a possible common stimulating factor. Copyright 1999 Academic Press.

  4. Investigation of Innervation Zone Shift with Continuous Dynamic Muscle Contraction

    Directory of Open Access Journals (Sweden)

    Ken Nishihara

    2013-01-01

    Full Text Available Innervation zone (IZ has been identified as the origin of action potential propagation in isometric contraction. However, IZ shifts with changes in muscle length during muscle activity. The IZ shift has been estimated using raw EMG signals. This study aimed to investigate the movement of IZ location during continuous dynamic muscle contraction, using a computer program. Subjects flexed their elbow joint as repetitive dynamic muscle contractions. EMG signals were recorded from the biceps brachii muscle using an eight-channel surface electrode array. Approximately 100 peaks from EMG signals were detected for each channel and summed to estimate the IZ location. For each subject, the estimated IZ locations were subtracted from the IZ location during isometric contractions with the elbow flexed at 90°. The results showed that the IZ moved significantly with elbow joint movement from 45° to 135°. However, IZ movement was biased with only a 3.9 mm IZ shift on average when the elbow angle was acute but a 16 mm IZ shift on average when it was obtuse. The movement of IZ location during continuous dynamic muscle contraction can be investigated using this signal processing procedure without subjective judgment.

  5. Synaptic Plasticity in Cardiac Innervation and Its Potential Role in Atrial Fibrillation

    OpenAIRE

    Jesse L. Ashton; Rebecca A. B. Burton; Gil Bub; Bruce H. Smaill; Bruce H. Smaill; Johanna M. Montgomery

    2018-01-01

    Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particularly in the neurons innervating the heart. The atria receive rich innervation from the autonomic branch of the peripheral nervous system. Sympathetic...

  6. Magnetic resonance imaging patterns of mononeuropathic denervation in muscles with dual innervation

    Energy Technology Data Exchange (ETDEWEB)

    Sneag, Darryl B.; Lee, Susan C.; Melisaratus, Darius P. [Hospital for Special Surgery, Department of Radiology and Imaging, New York, NY (United States); Feinberg, Joseph H. [Physical Medicine and Rehabilitation, Hospital for Special Surgery, New York, NY (United States); Amber, Ian [MedStar Georgetown University Hospital, Department of Radiology, DC, Washington (United States)

    2017-12-15

    Magnetic resonance imaging (MRI) of mononeuropathy in muscles with dual innervation depicts geographic denervation corresponding to the affected nerve. Knowledge of the normal distribution of a muscle's neural supply is clinically relevant as partial muscle denervation represents a potential imaging pitfall that can be confused with other pathology, such as muscle strain. This article reviews the normal innervation pattern of extremity muscles with dual supply, providing illustrative examples of mononeuropathy affecting such muscles. (orig.)

  7. Magnetic resonance imaging patterns of mononeuropathic denervation in muscles with dual innervation

    International Nuclear Information System (INIS)

    Sneag, Darryl B.; Lee, Susan C.; Melisaratus, Darius P.; Feinberg, Joseph H.; Amber, Ian

    2017-01-01

    Magnetic resonance imaging (MRI) of mononeuropathy in muscles with dual innervation depicts geographic denervation corresponding to the affected nerve. Knowledge of the normal distribution of a muscle's neural supply is clinically relevant as partial muscle denervation represents a potential imaging pitfall that can be confused with other pathology, such as muscle strain. This article reviews the normal innervation pattern of extremity muscles with dual supply, providing illustrative examples of mononeuropathy affecting such muscles. (orig.)

  8. Nuclear magnetic resonance studies of epithelial metabolism and function

    International Nuclear Information System (INIS)

    Balaban, R.S.

    1982-01-01

    Nuclear magnetic resonance (NMR) is a noninvasive technique for studying cellular metabolism and function. In this review the general applications and advantages of NMR will be discussed with specific reference to epithelial tissues. Phosphorus NMR investigations have been performed on epithelial tissues in vivo and in vitro; however, other detectable nuclei have not been utilized to date. Several new applications of phosphorus NMR to epithelial tissues are also discussed, including studies on isolated renal tubules and sheet epithelia

  9. Development of neuropeptide Y-mediated heart innervation in rats.

    Science.gov (United States)

    Masliukov, Petr M; Moiseev, Konstantin; Emanuilov, Andrey I; Anikina, Tatyana A; Zverev, Alexey A; Nozdrachev, Alexandr D

    2016-02-01

    Neuropeptide Y (NPY) plays a trophic role in the nervous and vascular systems and in cardiac hypertrophy. However, there is no report concerning the expression of NPY and its receptors in the heart during postnatal development. In the current study, immunohistochemistry and Western blot analysis was used to label NPY, and Y1R, Y2R, and Y5R receptors in the heart tissue and intramural cardiac ganglia from rats of different ages (newborn, 10 days old, 20 days old, 30 days old, 60 days old, 1 year old, and 2 years old).The obtained data suggest age-dependent changes of NPY-mediated heart innervation. The density of NPY-immunoreactive (IR) fibers was the least in newborn animals and increased in the first 20 days of life. In the atria of newborn and 10-day-old rats, NPY-IR fibers were more abundant compared with the ventricles. The vast majority of NPY-IR fibers also contained tyrosine hydroxylase, a key enzyme in catecholamine synthesis.The expression of Y1R increased between 10 and 20 days of life. Faint Y2R immunoreactivity was observed in the atria and ventricles of 20-day-old and older rats. In contrast, the highest level of the expression of Y5R was found in newborn pups comparing with more adult rats. All intramural ganglionic neurons were also Y1R-IR and Y5R-IR and Y2R-negative in all studied animals.Thus, the increasing of density of NPY-containing nerve fibers accompanies changes in relation of different subtypes of NPY receptors in the heart during development.

  10. Imbalance between sympathetic and sensory innervation in peritoneal endometriosis.

    Science.gov (United States)

    Arnold, Julia; Barcena de Arellano, Maria L; Rüster, Carola; Vercellino, Giuseppe F; Chiantera, Vito; Schneider, Achim; Mechsner, Sylvia

    2012-01-01

    To investigate possible mechanisms of pain pathophysiology in patients with peritoneal endometriosis, a clinical study on sensory and sympathetic nerve fibre sprouting in endometriosis was performed. Peritoneal lesions (n=40) and healthy peritoneum (n=12) were immunostained and analysed with anti-protein gene product 9.5 (PGP 9.5), anti-substance P (SP) and anti-tyrosine hydroxylase (TH), specific markers for intact nerve fibres, sensory nerve fibres and sympathetic nerve fibres, respectively, to identify the ratio of sympathetic and sensory nerve fibres. In addition, immune cell infiltrates in peritoneal endometriotic lesions were analysed and the nerve growth factor (NGF) and interleukin (IL)-1β expression was correlate with the nerve fibre density. Peritoneal fluids from patients with endometriosis (n=40) and without endometriosis (n=20) were used for the in vitro neuronal growth assay. Cultured chicken dorsal root ganglia (DRG) and sympathetic ganglia were stained with anti-growth associated protein 43 (anti-GAP 43), anti-SP and anti-TH. We could detect an increased sensory and decreased sympathetic nerve fibres density in peritoneal lesions compared to healthy peritoneum. Peritoneal fluids of patients with endometriosis compared to patients without endometriosis induced an increased sprouting of sensory neurites from DRG and decreased neurite outgrowth from sympathetic ganglia. In conclusion, this study demonstrates an imbalance between sympathetic and sensory nerve fibres in peritoneal endometriosis, as well as an altered modulation of peritoneal fluids from patients with endometriosis on sympathetic and sensory innervation which might directly be involved in the maintenance of inflammation and pain. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Innervation pattern of polycystic ovaries in the women.

    Science.gov (United States)

    Wojtkiewicz, Joanna; Jana, Barbara; Kozłowska, Anna; Crayton, Robert; Majewski, Mariusz; Zalecki, Michał; Baranowski, Włodzimierz; Radziszewski, Piotr

    2014-11-01

    The aim of the present study was to determine the changes in both the distribution pattern and density of nerve fibers containing dopamine β-hydroxylase (DβH), vesicular acetylcholine transporter (VAChT), neuronal nitric oxide synthase (nNOS), substance P (SP), calcitonin gene related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), somatostatin (SOM), galanin (GAL) and pituitary adenylate cyclase-activating polypeptide (PACAP) in the human polycystic ovaries. In the polycystic ovaries, when compared to the immunoreactions pattern observed in the control gonads, following changes were revealed: (1) an increase in the number of DβH-, VAChT-, VIP- or GAL-immunoreactive (IR) nerve fibers within the stroma as well as in the number of DβH-IR fibers near primordial follicles and medullar veins and venules; (2) a reduction in the number of nerve fibers containing nNOS, CGRP, SOM, PACAP within the stroma and in the numbers of CGRP-IR fibers around arteries; (3) an appearance of SP- and GAL-IR fibers around medullar and cortical arteries, arterioles, veins and venules, with except of GAL-IR fibers supplying medullar veins; and (4) the lack of nNOS-IR nerve fibers near primordial follicles and VIP-IR nerves around medullar arteries and arterioles. In conclusion, our results suggest that the changes in the innervation pattern of the polycystic ovaries in human may play an important role in the pathogenesis and/or course of this disorder. Copyright © 2014. Published by Elsevier B.V.

  12. Automatic localisation of innervation zones: a simulation study of the external anal sphincter.

    Science.gov (United States)

    Mesin, Luca; Gazzoni, Marco; Merletti, Roberto

    2009-12-01

    Traumas of the innervation zone (IZ) of the external anal sphincter (EAS), e.g. during delivery, can promote the development of faecal incontinence. Recently developed probes allow high-resolution detection of EMG signals from the EAS. The analysis of pelvic floor muscles by surface EMG (in particular, the estimation of the location of the IZ) has potential applications in the diagnosis and investigation of the mechanisms of incontinence. An automatic method (based on matched filter approach) for the estimation of the IZ distribution of EAS from surface EMG is discussed and tested using an analytical model of generation of EMG signals from sphincter muscles. Simulations are performed varying length of the fibres, thickness of the mucosa, position of the motor units, and force level. Different distributions of IZs are simulated. The performance of the proposed method in the estimation of the IZ distribution is affected by surface MUAP amplitude (as the estimation made by visual inspection), by mucosa thickness (performance decreases when fibre length is higher) and by different MU distributions. However, in general the method is able to identify the position of two IZ locations and can measure asymmetry of the IZ distribution. This strengthens the potential applications of high density surface EMG in the prevention and investigation of incontinence.

  13. Richly innervated soft tissues covering the superficial aspect of the extensor origin in patients with chronic painful tennis elbow – Implication for treatment?

    Science.gov (United States)

    Spang, C.; Alfredson, H.

    2017-01-01

    Background: Tennis elbow is difficult to treat. The results of surgical treatments are not convincing. Treatment studies on Achilles and patellar tendinopathy targeting the richly innervated and vascularized soft tissues outside the tendon have shown promising outcomes. The innervation patterns in the fibrous/fatty tissues superficially to the elbow extensor origin have not been clarified. Methods: Nine tissue specimens from the fibrous/fatty tissue covering the extensor origin was taken from seven patients (mean age: 45 years) undergoing surgical treatment for chronic painful tennis elbow. The specimens were stained for morphology (haematoxylin & eosin, H&E) and immunohistochemically for general nerve marker protein gene product 9.5 (PGP 9.5) and markers for sympathetic (tyrosine hydroxylase, TH) and sensory nerve fibres (calcitonin gene-related peptide, CGRP). Results: All specimens contained multiple blood vessels and nerve structures indicated by morphology and immunoreactions. There was a frequent occurrence of TH reactions, especially peri-vascularly, but also in nerve fascicles. Immunoreactions for CGRP were seen in nerve fascicles and isolated nerve fibres. Conclusion: The results provide new information on the innervation patterns of the superficial tissues of the extensor origin and their potential as source of tennis elbow pain. Level of Evidence: IV. PMID:28574416

  14. Richly innervated soft tissues covering the superficial aspect of the extensor origin in patients with chronic painful tennis elbow - Implication for treatment?

    Science.gov (United States)

    Spang, C; Alfredson, H

    2017-06-01

    Tennis elbow is difficult to treat. The results of surgical treatments are not convincing. Treatment studies on Achilles and patellar tendinopathy targeting the richly innervated and vascularized soft tissues outside the tendon have shown promising outcomes. The innervation patterns in the fibrous/fatty tissues superficially to the elbow extensor origin have not been clarified. Nine tissue specimens from the fibrous/fatty tissue covering the extensor origin was taken from seven patients (mean age: 45 years) undergoing surgical treatment for chronic painful tennis elbow. The specimens were stained for morphology (haematoxylin and eosin, H and E) and immunohistochemically for general nerve marker protein gene product 9.5 (PGP 9.5) and markers for sympathetic (tyrosine hydroxylase, TH) and sensory nerve fibres (calcitonin gene-related peptide, CGRP). All specimens contained multiple blood vessels and nerve structures indicated by morphology and immunoreactions. There was a frequent occurrence of TH reactions, especially peri-vascularly, but also in nerve fascicles. Immunoreactions for CGRP were seen in nerve fascicles and isolated nerve fibres. The results provide new information on the innervation patterns of the superficial tissues of the extensor origin and their potential as source of tennis elbow pain. IV.

  15. Taste Bud-Derived BDNF Is Required to Maintain Normal Amounts of Innervation to Adult Taste Buds123

    Science.gov (United States)

    Meng, Lingbin; Ohman-Gault, Lisa; Ma, Liqun

    2015-01-01

    Abstract Gustatory neurons transmit chemical information from taste receptor cells, which reside in taste buds in the oral cavity, to the brain. As adult taste receptor cells are renewed at a constant rate, nerve fibers must reconnect with new taste receptor cells as they arise. Therefore, the maintenance of gustatory innervation to the taste bud is an active process. Understanding how this process is regulated is a fundamental concern of gustatory system biology. We speculated that because brain-derived neurotrophic factor (BDNF) is required for taste bud innervation during development, it might function to maintain innervation during adulthood. If so, taste buds should lose innervation when Bdnf is deleted in adult mice. To test this idea, we first removed Bdnf from all cells in adulthood using transgenic mice with inducible CreERT2 under the control of the Ubiquitin promoter. When Bdnf was removed, approximately one-half of the innervation to taste buds was lost, and taste buds became smaller because of the loss of taste bud cells. Individual taste buds varied in the amount of innervation each lost, and those that lost the most innervation also lost the most taste bud cells. We then tested the idea that that the taste bud was the source of this BDNF by reducing Bdnf levels specifically in the lingual epithelium and taste buds. Taste buds were confirmed as the source of BDNF regulating innervation. We conclude that BDNF expressed in taste receptor cells is required to maintain normal levels of innervation in adulthood. PMID:26730405

  16. Taste Bud-Derived BDNF Is Required to Maintain Normal Amounts of Innervation to Adult Taste Buds.

    Science.gov (United States)

    Meng, Lingbin; Ohman-Gault, Lisa; Ma, Liqun; Krimm, Robin F

    2015-01-01

    Gustatory neurons transmit chemical information from taste receptor cells, which reside in taste buds in the oral cavity, to the brain. As adult taste receptor cells are renewed at a constant rate, nerve fibers must reconnect with new taste receptor cells as they arise. Therefore, the maintenance of gustatory innervation to the taste bud is an active process. Understanding how this process is regulated is a fundamental concern of gustatory system biology. We speculated that because brain-derived neurotrophic factor (BDNF) is required for taste bud innervation during development, it might function to maintain innervation during adulthood. If so, taste buds should lose innervation when Bdnf is deleted in adult mice. To test this idea, we first removed Bdnf from all cells in adulthood using transgenic mice with inducible CreERT2 under the control of the Ubiquitin promoter. When Bdnf was removed, approximately one-half of the innervation to taste buds was lost, and taste buds became smaller because of the loss of taste bud cells. Individual taste buds varied in the amount of innervation each lost, and those that lost the most innervation also lost the most taste bud cells. We then tested the idea that that the taste bud was the source of this BDNF by reducing Bdnf levels specifically in the lingual epithelium and taste buds. Taste buds were confirmed as the source of BDNF regulating innervation. We conclude that BDNF expressed in taste receptor cells is required to maintain normal levels of innervation in adulthood.

  17. Anatomic Patterns of Renal Arterial Sympathetic Innervation: New Aspects for Renal Denervation.

    Science.gov (United States)

    Imnadze, Guram; Balzer, Stefan; Meyer, Baerbel; Neumann, Joerg; Krech, Rainer Horst; Thale, Joachim; Franz, Norbert; Warnecke, Henning; Awad, Khaled; Hayek, Salim S; Devireddy, Chandan

    2016-12-01

    Initial studies of catheter-based renal arterial sympathetic denervation to lower blood pressure in resistant hypertensive patients renewed interest in the sympathetic nervous system's role in the pathogenesis of hypertension. However, the SYMPLICITY HTN-3 study failed to meet its prespecified blood pressure lowering efficacy endpoint. To date, only a limited number of studies have described the microanatomy of renal nerves, of which, only two involve humans. Renal arteries were harvested from 15 cadavers from the Klinikum Osnabruck and Schuchtermann Klinik, Bad Rothenfelde. Each artery was divided longitudinally in equal thirds (proximal, middle, and distal), with each section then divided into equal superior, inferior, anterior, and posterior quadrants, which were then stained. Segments containing no renal nerves were given a score value = 0, 1-2 nerves with diameter 4 nerves or nerve diameter ≥600 µm a score = 3. A total of 22 renal arteries (9 right-sided, 13 left-sided) were suitable for examination. Overall, 691 sections of 5 mm thickness were prepared. Right renal arteries had significantly higher mean innervation grade (1.56 ± 0.85) compared to left renal arteries (1.09 ± 0.87) (P renal artery has significantly higher innervation scores than the left. The anterior and superior quadrants of the renal arteries scored higher in innervation than the posterior and inferior quadrants did. The distal third of the renal arteries are more innervated than the more proximal segments. These findings warrant further evaluation of the spatial innervation patterns of the renal artery in order to understand how it may enhance catheter-based renal arterial denervation procedural strategy and outcomes. The SYMPLICITY HTN-3 study dealt a blow to the idea of the catheter-based renal arterial sympathetic denervation. We investigated the location and patterns of periarterial renal nerves in cadaveric human renal arteries. To quantify the density of the

  18. Neurons of self-defence: neuronal innervation of the exocrine defence glands in stick insects.

    Science.gov (United States)

    Stolz, Konrad; von Bredow, Christoph-Rüdiger; von Bredow, Yvette M; Lakes-Harlan, Reinhard; Trenczek, Tina E; Strauß, Johannes

    2015-01-01

    Stick insects (Phasmatodea) use repellent chemical substances (allomones) for defence which are released from so-called defence glands in the prothorax. These glands differ in size between species, and are under neuronal control from the CNS. The detailed neural innervation and possible differences between species are not studied so far. Using axonal tracing, the neuronal innervation is investigated comparing four species. The aim is to document the complexity of defence gland innervation in peripheral nerves and central motoneurons in stick insects. In the species studied here, the defence gland is innervated by the intersegmental nerve complex (ISN) which is formed by three nerves from the prothoracic (T1) and suboesophageal ganglion (SOG), as well as a distinct suboesophageal nerve (Nervus anterior of the suboesophageal ganglion). In Carausius morosus and Sipyloidea sipylus, axonal tracing confirmed an innervation of the defence glands by this N. anterior SOG as well as N. anterior T1 and N. posterior SOG from the intersegmental nerve complex. In Peruphasma schultei, which has rather large defence glands, only the innervation by the N. anterior SOG was documented by axonal tracing. In the central nervous system of all species, 3-4 neuron types are identified by axonal tracing which send axons in the N. anterior SOG likely innervating the defence gland as well as adjacent muscles. These neurons are mainly suboesophageal neurons with one intersegmental neuron located in the prothoracic ganglion. The neuron types are conserved in the species studied, but the combination of neuron types is not identical. In addition, the central nervous system in S. sipylus contains one suboesophageal and one prothoracic neuron type with axons in the intersegmental nerve complex contacting the defence gland. Axonal tracing shows a very complex innervation pattern of the defence glands of Phasmatodea which contains different neurons in different nerves from two adjacent body segments

  19. Reduced Sympathetic Innervation in Endometriosis is Associated to Semaphorin 3C and 3F Expression.

    Science.gov (United States)

    Scheerer, Claudia; Frangini, Sergio; Chiantera, Vito; Mechsner, Sylvia

    2017-09-01

    Endometriosis is a chronic inflammatory disease and one of the most common causes of pelvic pain. The mechanisms underlying pain emergence or chronic inflammation during endometriosis remain unknown. Several chronic inflammatory diseases including endometriosis show reduced amounts of noradrenergic nerve fibers. The source of the affected innervation is still unclear. Semaphorins represent potential elicitors, due to their known role as axonal guidance cues, and are suggested as nerve repellent factors in different chronic inflammatory diseases. Therefore, semaphorins might influence the progress of neuroinflammatory mechanisms during endometriosis. Here, we analyzed the noradrenergic innervation and the expression of the specific semaphorins and receptors possibly involved in the neuroimmunomodulation in endometriosis. Our studies revealed an affected innervation and a significant increase of semaphorins and their receptors in peritoneal endometriotic tissue. Thereby, the expression of the receptors was identified on the membrane of noradrenergic nerve fibers and vessels. Macrophages and activated fibroblasts were found in higher density levels and additionally express semaphorins in peritoneal endometriotic tissue. Inflammation leads to an increased release of immune cells, which secrete a variety of inflammatory factors capable of affecting innervation. Therefore, our data suggests that the chronic inflammatory condition in endometriosis might contribute to the increase of semaphorins, which could possibly affect the innervation in peritoneal endometriosis.

  20. General Information about Ovarian Epithelial Cancer

    Science.gov (United States)

    ... diagnosed, tests are done to find out if cancer cells have spread within the ovaries or to other parts of the body. The ... single ovary or fallopian tube. In stage IB, cancer is found inside both ovaries or fallopian tubes. In stage IC, cancer is ...

  1. Intrinsic and extrinsic innervation of the heart in zebrafish (Danio rerio).

    Science.gov (United States)

    Stoyek, Matthew R; Croll, Roger P; Smith, Frank M

    2015-08-01

    In the vertebrate heart the intracardiac nervous system is the final common pathway for autonomic control of cardiac output, but the neuroanatomy of this system is not well understood. In this study we investigated the innervation of the heart in a model vertebrate, the zebrafish. We used antibodies against acetylated tubulin, human neuronal protein C/D, choline acetyltransferase, tyrosine hydroxylase, neuronal nitric oxide synthase, and vasoactive intestinal polypeptide to visualize neural elements and their neurotransmitter content. Most neurons were located at the venous pole in a plexus around the sinoatrial valve; mean total number of cells was 197 ± 23, and 92% were choline acetyltransferase positive, implying a cholinergic role. The plexus contained cholinergic, adrenergic, and nitrergic axons and vasoactive intestinal polypeptide-positive terminals, some innervating somata. Putative pacemaker cells near the plexus showed immunoreactivity for hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and the transcription factor Islet-1 (Isl1). The neurotracer neurobiotin showed that extrinsic axons from the left and right vagosympathetic trunks innervated the sinoatrial plexus proximal to their entry into the heart; some extrinsic axons from each trunk also projected into the medial dorsal plexus region. Extrinsic axons also innervated the atrial and ventricular walls. An extracardiac nerve trunk innervated the bulbus arteriosus and entered the arterial pole of the heart to innervate the proximal ventricle. We have shown that the intracardiac nervous system in the zebrafish is anatomically and neurochemically complex, providing a substrate for autonomic control of cardiac effectors in all chambers. © 2015 Wiley Periodicals, Inc.

  2. Quantified distribution of the noradrenaline innervation in the hippocampus of adult rat

    International Nuclear Information System (INIS)

    Oleskevich, S.; Descarries, L.; Lacaille, J.C.

    1989-01-01

    A recently developed radioautographic technique, based on the uptake labeling of monoamine terminals in vitro, was used to quantify the noradrenaline (NA) innervation in adult rat hippocampus. After incubation of brain slices with 1 microM 3H-NA, the NA varicosities were visualized as small aggregates of silver grains, in light microscope radioautographs prepared at 3 equidistant horizontal levels across the ventral 2/3 of the hippocampus. Using a computer-assisted image analyzer, counts were obtained from the subiculum (SUB), 3 sectors of Ammon's horn (CA1, CA3-a, CA3-b) and 3 sectors of the dentate gyrus (DG-medial blade, crest, and lateral blade), every lamina being sampled in each region. After a double correction for duration of radioautographic exposure and section thickness, and following measurement of varicosity diameter in electron microscope radioautographs, it was possible to express these results in number of terminals per volumetric unit of tissue. It was thus found that the overall density of hippocampal NA innervation averages 2.1 million varicosities/mm3 of tissue, a value almost twice as high as that in cerebral cortex. This innervation is 20% denser ventrally than dorsally and is heterogeneous both in terms of regional and laminar distribution. SUB and DG are more strongly innervated than Ammon's horn, wherein CA1 has the lowest overall density. In SUB and CA1, there is a clear predilection of NA varicosities for the stratum moleculare. In CA3, there is a narrow band of even stronger innervation in the stratum radiatum, near the apical border of the stratum pyramidale, contrasting with a 3 times lower density in this cell layer and the stratum oriens. In DG, the NA innervation is again the weakest in the cell body layer and exhibits an almost 3-fold greater density in the polymorph layer, the highest of all hippocampus

  3. Innervation pattern of the suprascapular nerve within supraspinatus: a three-dimensional computer modeling study.

    Science.gov (United States)

    Hermenegildo, J A; Roberts, S L; Kim, S Y

    2014-05-01

    The relationship between the innervation pattern of the suprascapular nerve (SSN) and the muscle architecture of supraspinatus has not been thoroughly investigated. The supraspinatus is composed of two architecturally distinct regions: anterior and posterior. Each of these regions is further subdivided into three parts: superficial, middle and deep. The purpose of this study was to investigate the course of the SSN throughout the volume of supraspinatus and to relate the intramuscular branches to the distinct regions and parts of the supraspinatus. The SSN was dissected in thirty formalin embalmed cadaveric specimens and digitized throughout the muscle volume in six of those specimens. The digitized data were modeled using Autodesk(®) Maya(®) 2011. The three-dimensional (3D) models were used to relate the intramuscular innervation pattern to the muscle and tendon architecture defined by Kim et al. (2007, Clin Anat 20:648-655). The SSN bifurcated into two main trunks: medial and lateral. All parts of the anterior region were predominantly innervated by the medial trunk and its proximal and medial branches, whereas all parts of the posterior region predominantly by the lateral trunk and its posterolateral and/or posteromedial branches. The posterior region also received innervation from the proximal branch of the medial trunk in half of the specimens. These findings provide evidence that the anterior and posterior regions are distinct with respect to their innervation. The 3D map of the innervation pattern will aid in planning future clinical studies investigating muscle activation patterns and provide insight into possible injury of the nerve with supraspinatus pathology and surgical techniques. Copyright © 2013 Wiley Periodicals, Inc.

  4. Cultured embryonic non-innervated mouse muzzle is capable of generating a whisker pattern.

    Science.gov (United States)

    Andrés, F L; Van Der Loos, H

    1983-01-01

    The whisker pattern on the muzzle of the mouse is mapped in the contralateral parietal neocortex, each whisker follicle projecting to its own multineuronal unit ('barrel'). To determine the role, if any, of the peripheral innervation in the establishment of the vibrissal array, we cultured non-innervated prospective whiskerpads from 9- and 10-day-old embryos, mostly on chorioallantoic membrane. The results show that skin, alone, is capable of generating the whisker pattern, thus adducing a strong argument for the hypothesis that the central brain maps have their origin in the periphery. Copyright © 1983. Published by Elsevier Ltd.

  5. Associations between xerostomia, histopathological alterations, and autonomic innervation of labial salivary glands in men in late midlife

    DEFF Research Database (Denmark)

    Sørensen, Christiane Elisabeth; Larsen, Jytte Overgaard; Reibel, Jesper

    2014-01-01

    connective tissue. Acinar atrophy and fibrosis were negatively correlated with the parenchymal innervation and positively related to diffuse inflammation. CONCLUSIONS: The results from the present study indicate that aspects of the autonomic innervation of labial salivary glands may play a role...

  6. Relationships between cardiac innervation/perfusion imbalance and ventricular arrhythmias: impact on invasive electrophysiological parameters and ablation procedures

    International Nuclear Information System (INIS)

    Gimelli, Alessia; Menichetti, Francesca; Soldati, Ezio; Liga, Riccardo; Vannozzi, Andrea; Bongiorni, Maria Grazia; Marzullo, Paolo

    2016-01-01

    To assess the relationship between regional myocardial perfusion and sympathetic innervation parameters at myocardial scintigraphy and intra-cavitary electrophysiological data in patients with ventricular arrhythmias (VA) submitted to invasive electrophysiological study and ablation procedure. Sixteen subjects underwent invasive electrophysiological study with electroanatomical mapping (EAM) followed by trans-catheter ablations of VA. Before ablation all patients were studied with a combined evaluation of regional myocardial perfusion and sympathetic innervation by means of tomographic "9"9"mTc-tetrofosmin and "1"2"3I- metaiodobenzylguanidine cadmium-zinc-telluride (CZT) scintigraphies, respectively. Off-line spatial co-registration of CZT perfusion and innervation data with the three-dimensional EAM reconstruction was performed in every patient. CZT revealed the presence of myocardial scar in 55 (20 %) segments. Of the viable myocardial segments, 131 (60 %) presented a preserved adrenergic innervation, while 86 (40 %) showed a significantly depressed innervation (i.e. innervation/perfusion mismatch). On EAM, the invasively measured intra-cavitary voltage was significantly lower in scarred segments than in viable ones (1.7 ± 1.5 mV vs. 4.0 ± 2.2 mV, P < 0.001). Interestingly, among the viable segments, those showing an innervation/perfusion mismatch presented a significantly lower intra-cavitary voltage than those with preserved innervation (1.9 ± 2.5 mV vs. 4.7 ± 2.3 mV, P < 0.001). Intra-cardiac ablation was performed in 63 (23 %) segments. On multivariate analysis, after correction for scar burden, the segments showing an innervation/perfusion mismatch remained the most frequent ablation targets (OR 5.6, 95 % CI 1.5-20.8; P = 0.009). In patients with VA, intra-cavitary electrical abnormalities frequently originate at the level of viable myocardial segments with depressed sympathetic innervation that frequently represents the ultimate ablation target. (orig.)

  7. Relationships between cardiac innervation/perfusion imbalance and ventricular arrhythmias: impact on invasive electrophysiological parameters and ablation procedures

    Energy Technology Data Exchange (ETDEWEB)

    Gimelli, Alessia [Fondazione Toscana Gabriele Monasterio, Pisa (Italy); Menichetti, Francesca; Soldati, Ezio; Liga, Riccardo; Vannozzi, Andrea; Bongiorni, Maria Grazia [University Hospital of Pisa, Cardio-Thoracic and Vascular Department, Pisa (Italy); Marzullo, Paolo [Fondazione Toscana Gabriele Monasterio, Pisa (Italy); CNR, Institute of Clinical Physiology, Pisa (Italy)

    2016-12-15

    To assess the relationship between regional myocardial perfusion and sympathetic innervation parameters at myocardial scintigraphy and intra-cavitary electrophysiological data in patients with ventricular arrhythmias (VA) submitted to invasive electrophysiological study and ablation procedure. Sixteen subjects underwent invasive electrophysiological study with electroanatomical mapping (EAM) followed by trans-catheter ablations of VA. Before ablation all patients were studied with a combined evaluation of regional myocardial perfusion and sympathetic innervation by means of tomographic {sup 99m}Tc-tetrofosmin and {sup 123}I- metaiodobenzylguanidine cadmium-zinc-telluride (CZT) scintigraphies, respectively. Off-line spatial co-registration of CZT perfusion and innervation data with the three-dimensional EAM reconstruction was performed in every patient. CZT revealed the presence of myocardial scar in 55 (20 %) segments. Of the viable myocardial segments, 131 (60 %) presented a preserved adrenergic innervation, while 86 (40 %) showed a significantly depressed innervation (i.e. innervation/perfusion mismatch). On EAM, the invasively measured intra-cavitary voltage was significantly lower in scarred segments than in viable ones (1.7 ± 1.5 mV vs. 4.0 ± 2.2 mV, P < 0.001). Interestingly, among the viable segments, those showing an innervation/perfusion mismatch presented a significantly lower intra-cavitary voltage than those with preserved innervation (1.9 ± 2.5 mV vs. 4.7 ± 2.3 mV, P < 0.001). Intra-cardiac ablation was performed in 63 (23 %) segments. On multivariate analysis, after correction for scar burden, the segments showing an innervation/perfusion mismatch remained the most frequent ablation targets (OR 5.6, 95 % CI 1.5-20.8; P = 0.009). In patients with VA, intra-cavitary electrical abnormalities frequently originate at the level of viable myocardial segments with depressed sympathetic innervation that frequently represents the ultimate ablation target

  8. A New Wavelet-Based ECG Delineator for the Evaluation of the Ventricular Innervation

    DEFF Research Database (Denmark)

    Cesari, Matteo; Mehlsen, Jesper; Mehlsen, Anne-Birgitte

    2017-01-01

    T-wave amplitude (TWA) has been proposed as a marker of the innervation of the myocardium. Until now, TWA has been calculated manually or with poor algorithms, thus making its use not efficient in a clinical environment. We introduce a new wavelet-based algorithm for the delineation QRS complexes...

  9. Innervation Patterns of Sea Otter (Enhydra lutris Mystacial Follicle-Sinus Complexes

    Directory of Open Access Journals (Sweden)

    Christopher Douglas Marshall

    2014-10-01

    Full Text Available Sea otters (Enhydra lutris are the most recent group of mammals to return to the sea, and may exemplify divergent somatosensory tactile systems among mammals. Therefore, we quantified the mystacial vibrissal array of sea otters and histologically processed follicle-sinus complexes (F-SCs to test the hypotheses that the number of myelinated axons per F-SC is greater than that found for terrestrial mammalian vibrissae and that their organization and microstructure converge with those of pinniped vibrissae. A mean of 120.5 vibrissae were arranged rostrally on a broad, blunt muzzle in 7-8 rows and 9-13 columns. The F-SCs of sea otters are tripartite in their organization and similar in microstructure to pinnipeds rather than terrestrial species. Each F-SC was innervated by a mean 1339±408.3 axons. Innervation to the entire mystacial vibrissal array was estimated at 161,313 axons. Our data support the hypothesis that the disproportionate expansion of the coronal gyrus in somatosensory cortex of sea otters is related to the high innervation investment of the mystacial vibrissal array, and that quantifying innervation investment is a good proxy for tactile sensitivity. We predict that the tactile performance of sea otter mystacial vibrissae is comparable to that of harbor seals, sea lions and walruses¬.

  10. Synaptic Plasticity in Cardiac Innervation and Its Potential Role in Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Jesse L. Ashton

    2018-03-01

    Full Text Available Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particularly in the neurons innervating the heart. The atria receive rich innervation from the autonomic branch of the peripheral nervous system. Sympathetic neurons are clustered in stellate and cervical ganglia alongside the spinal cord and extend fibers to the heart directly innervating the myocardium. These neurons are major drivers of hyperactive sympathetic activity observed in heart disease, ventricular arrhythmias, and sudden cardiac death. Both pre- and postsynaptic changes have been observed to occur at synapses formed by sympathetic ganglion neurons, suggesting that plasticity at sympathetic neuro-cardiac synapses is a major contributor to arrhythmias. Less is known about the plasticity in parasympathetic neurons located in clusters on the heart surface. These neuronal clusters, termed ganglionated plexi, or “little brains,” can independently modulate neural control of the heart and stimulation that enhances their excitability can induce arrhythmia such as atrial fibrillation. The ability of these neurons to alter parasympathetic activity suggests that plasticity may indeed occur at the synapses formed on and by ganglionated plexi neurons. Such changes may not only fine-tune autonomic innervation of the heart, but could also be a source of maladaptive plasticity during atrial fibrillation.

  11. Bilateral familial vertical Duane Syndrome with synergistic convergence, aberrant trigeminal innervation, and facial hypoplasia

    Directory of Open Access Journals (Sweden)

    Malvika Gupta

    2014-01-01

    Full Text Available A 5-year-old girl presented with bilateral familial vertical  Duane retraction syndrome with alternating esotropia, elevation deficit, Marcus gunn phenomenon, and facial hypoplasia. Abnormal adducting downshoots on attempting abduction suggestive of a synergistic convergence were noted. Hypothesis suggests aberrant innervations or peripheral anatomic connections between inferior and medial recti.

  12. The role of Sema3–Npn-1 signaling during diaphragm innervation and muscle development

    Science.gov (United States)

    Huettl, Rosa-Eva; Hanuschick, Philipp; Amend, Anna-Lena; Alberton, Paolo; Aszodi, Attila; Huber, Andrea B.

    2016-01-01

    ABSTRACT Correct innervation of the main respiratory muscle in mammals, namely the thoracic diaphragm, is a crucial pre-requisite for the functionality of this muscle and the viability of the entire organism. Systemic impairment of Sema3A–Npn-1 (Npn-1 is also known as NRP1) signaling causes excessive branching of phrenic nerves in the diaphragm and into the central tendon region, where the majority of misguided axons innervate ectopic musculature. To elucidate whether these ectopic muscles are a result of misguidance of myoblast precursors due to the loss of Sema3A–Npn-1 signaling, we conditionally ablated Npn-1 in somatic motor neurons, which led to a similar phenotype of phrenic nerve defasciculation and, intriguingly, also formation of innervated ectopic muscles. We therefore hypothesize that ectopic myocyte fusion is caused by additional factors released by misprojecting growth cones. Slit2 and its Robo receptors are expressed by phrenic motor axons and migrating myoblasts, respectively, during innervation of the diaphragm. In vitro analyses revealed a chemoattractant effect of Slit2 on primary diaphragm myoblasts. Thus, we postulate that factors released by motor neuron growth cones have an influence on the migration properties of myoblasts during establishment of the diaphragm. PMID:27466379

  13. The role of the autonomic nervous liver innervation in the control of energy metabolism

    NARCIS (Netherlands)

    Yi, Chun-Xia; la Fleur, Susanne E.; Fliers, Eric; Kalsbeek, Andries

    2010-01-01

    Despite a longstanding research interest ever since the early work by Claude Bernard, the functional significance of autonomic liver innervation, either sympathetic or parasympathetic, is still ill defined. This scarcity of information not only holds for the brain control of hepatic metabolism, but

  14. Innervating sympathetic neurons regulate heart size and the timing of cardiomyocyte cell cycle withdrawal.

    Science.gov (United States)

    Kreipke, R E; Birren, S J

    2015-12-01

    Sympathetic drive to the heart is a key modulator of cardiac function and interactions between heart tissue and innervating sympathetic fibres are established early in development. Significant innervation takes place during postnatal heart development, a period when cardiomyocytes undergo a rapid transition from proliferative to hypertrophic growth. The question of whether these innervating sympathetic fibres play a role in regulating the modes of cardiomyocyte growth was investigated using 6-hydroxydopamine (6-OHDA) to abolish early sympathetic innervation of the heart. Postnatal chemical sympathectomy resulted in rats with smaller hearts, indicating that heart growth is regulated by innervating sympathetic fibres during the postnatal period. In vitro experiments showed that sympathetic interactions resulted in delays in markers of cardiomyocyte maturation, suggesting that changes in the timing of the transition from hyperplastic to hypertrophic growth of cardiomyocytes could underlie changes in heart size in the sympathectomized animals. There was also an increase in the expression of Meis1, which has been linked to cardiomyocyte cell cycle withdrawal, suggesting that sympathetic signalling suppresses cell cycle withdrawal. This signalling involves β-adrenergic activation, which was necessary for sympathetic regulation of cardiomyocyte proliferation and hypertrophy. The effect of β-adrenergic signalling on cardiomyocyte hypertrophy underwent a developmental transition. While young postnatal cardiomyocytes responded to isoproterenol (isoprenaline) with a decrease in cell size, mature cardiomyocytes showed an increase in cell size in response to the drug. Together, these results suggest that early sympathetic effects on proliferation modulate a key transition between proliferative and hypertrophic growth of the heart and contribute to the sympathetic regulation of adult heart size. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  15. Early Corneal Innervation and Trigeminal Alterations in Parkinson Disease: A Pilot Study.

    Science.gov (United States)

    Arrigo, Alessandro; Rania, Laura; Calamuneri, Alessandro; Postorino, Elisa Imelde; Mormina, Enricomaria; Gaeta, Michele; Marino, Silvia; Di Lorenzo, Giuseppe; Quartarone, Angelo; Anastasi, Giuseppe; Puzzolo, Domenico; Aragona, Pasquale

    2018-04-01

    To describe corneal innervation and trigeminal alterations in drug-naive patients with Parkinson disease (PD). A case series study was conducted by recruiting 3 early drug-naive patients with PD, 2 men and 1 woman (age: 72, 68, and 66, respectively). Ophthalmologic assessment included Ocular Surface Disease Index questionnaire, visual acuity by the logarithm of the minimum angle of resolution score, pupillary light reflexes, extrinsic ocular movements, corneal sensitivity, and slit-lamp examination. Corneal innervation parameter changes were evaluated in vivo using the Confoscan 4 confocal microscope, and they were compared with a control data set. The Heidelberg Retina Tomograph 3 (HRT3) has been used to assess retinal alterations in our patients, if compared with normal range values provided by the HRT3. Moreover, 3T magnetic resonance imaging (MRI) analysis of water diffusion property changes of trigeminal nerves was performed. All data were analyzed and compared with 2 control data sets made by 14 age-matched controls. Patients with PD showed profound alterations of corneal innervation and of trigeminal diffusion MRI parameters, compared with controls. Strong differences (PD vs. controls) were found for deep nerve tortuosity (Kallinikos mean 19.94 vs. 2.13) and the number of beadings (mean 34.2 vs. 15.5). HRT3 retinal evaluation revealed less structural changes compared with the normal range. Diffusion MRI showed profound changes of white matter diffusion properties (PD vs. controls), with fractional anisotropy decrement (mean 0.3029 vs. 0.3329) and mean diffusivity increment (mean 0.00127 vs. 0.00106). Corneal innervation changes might occur earlier in patients with PD than in retinal ones. Confocal corneal innervation analysis might provide possible early biomarkers for a better PD evaluation and for its earlier diagnosis.

  16. Double muscle innervation using end-to-side neurorrhaphy in rats

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    Elisangela Jeronymo Stipp-Brambilla

    Full Text Available CONTEXT AND OBJECTIVE: One of the techniques used for treating facial paralysis is double muscle innervation using end-to-end neurorrhaphy with sectioning of healthy nerves. The aim of this study was to evaluate whether double muscle innervation by means of end-to-side neurorrhaphy could occur, with maintenance of muscle innervation. DESIGN AND SETTING: Experimental study developed at the Experimental Research Center, Faculdade de Medicina de Botucatu, Unesp. METHODS: One hundred rats were allocated to five groups as follows: G1, control group; G2, the peroneal nerve was sectioned; G3, the tibial nerve was transected and the proximal stump was end-to-side sutured to the intact peroneal nerve; G4, 120 days after the G3 surgery, the peroneal nerve was sectioned proximally to the neurorrhaphy; G5, 120 days after the G3 surgery, the peroneal and tibial nerves were sectioned proximally to the neurorrhaphy. RESULTS: One hundred and fifty days after the surgery, G3 did not show any change in tibial muscle weight or muscle fiber diameter, but the axonal fiber diameter in the peroneal nerve distal to the neurorrhaphy had decreased. Although G4 showed atrophy of the cranial tibial muscle 30 days after sectioning the peroneal nerve, the electrophysiological test results and axonal diameter measurement confirmed that muscle reinnervation had occurred. CONCLUSION: These findings suggest that double muscle innervation did not occur through end-to-side neurorrhaphy; the tibial nerve was not able to maintain muscle innervation after the peroneal nerve had been sectioned, although muscle reinnervation was found to have occurred, 30 days after the peroneal nerve had been sectioned.

  17. Normal morphogenesis of epithelial tissues and progression of epithelial tumors

    Science.gov (United States)

    Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A.

    2011-01-01

    Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted. PMID:21898857

  18. Morphology and innervation of the diaphragma of Myrmecophaga tridactyla.

    Science.gov (United States)

    Miglino, M A; de Santis-Prada, I L; Di Dio, L J

    1991-01-01

    The diaphragma of 4 "Myrmecophaga tridactyla" was described. The diaphragma follows the general pattern of EDENTATA, but it has special features which make it possible to differentiate it from that of "Bradypus tridactylus.

  19. Afferent Innervation, Muscle Spindles, and Contractures Following Neonatal Brachial Plexus Injury in a Mouse Model.

    Science.gov (United States)

    Nikolaou, Sia; Hu, Liangjun; Cornwall, Roger

    2015-10-01

    We used an established mouse model of elbow flexion contracture after neonatal brachial plexus injury (NBPI) to test the hypothesis that preservation of afferent innervation protects against contractures and is associated with preservation of muscle spindles and ErbB signaling. A model of preganglionic C5 through C7 NBPI was first tested in mice with fluorescent axons using confocal imaging to confirm preserved afferent innervation of spindles despite motor end plate denervation. Preganglionic and postganglionic injuries were then created in wild-type mice. Four weeks later, we assessed total and afferent denervation of the elbow flexors by musculocutaneous nerve immunohistochemistry. Biceps muscle volume and cross-sectional area were measured by micro computed tomography. An observer who was blinded to the study protocol measured elbow flexion contractures. Biceps spindle and muscle fiber morphology and ErbB signaling pathway activity were assessed histologically and immunohistochemically. Preganglionic and postganglionic injuries caused similar total denervation and biceps muscle atrophy. However, after preganglionic injuries, afferent innervation was partially preserved and elbow flexion contractures were significantly less severe. Spindles degenerated after postganglionic injury but were preserved after preganglionic injury. ErbB signaling was inactivated in denervated spindles after postganglionic injury but ErbB signaling activity was preserved in spindles after preganglionic injury with retained afferent innervation. Preganglionic and postganglionic injuries were associated with upregulation of ErbB signaling in extrafusal muscle fibers. Contractures after NBPI are associated with muscle spindle degeneration and loss of spindle ErbB signaling activity. Preservation of afferent innervation maintained spindle development and ErbB signaling activity, and protected against contractures. Pharmacologic modulation of ErbB signaling, which is being investigated as a

  20. Multifocal Epithelial Hyperplasia.

    Science.gov (United States)

    Agnew, Caitlin; Alexander, Sherene; Prabhu, Neeta

    2017-01-15

    Multifocal epithelial hyperplasia is a rare disease associated with human papilloma virus types 13 and 32. Diagnosis is based on clinical and histopathological findings, and most lesions are asymptomatic and regress spontaneously with time. The purpose of this paper is to describe a five-year-old girl who presented with multiple intraoral lesions on the buccal mucosa and tongue, which regressed spontaneously in 15 months.

  1. Anomalous Innervation of the Median Nerve in the Arm in the Absence of the Musculocutaneous Nerve

    Directory of Open Access Journals (Sweden)

    Khursheed Raza

    2017-03-01

    Full Text Available The brachial plexus innervates the upper extremities. While variations in the formation of the brachial plexus and its terminal branches are quite common, it is uncommon for the median nerve to innervate the muscles of the arm. During the dissection of an elderly male cadaver at the Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India, in 2016, the coracobrachialis muscle was found to be supplied by a direct branch from the lateral root of the median nerve and the musculocutaneous nerve was absent. The branches of the median nerve supplied the biceps brachii and brachialis muscles and the last branch continued as the lateral cutaneous nerve of the forearm. These variations may present atypically in cases of arm flexor paralysis or sensory loss on the lateral forearm. Knowledge of these variations is important in surgeries and during the administration of regional anaesthesia near the shoulder joint and upper arm.

  2. Innervation of taste buds revealed with Brainbow-labeling in mouse.

    Science.gov (United States)

    Zaidi, Faisal N; Cicchini, Vanessa; Kaufman, Daniel; Ko, Elizabeth; Ko, Abraham; Van Tassel, Heather; Whitehead, Mark C

    2016-12-01

    Nerve fibers that surround and innervate the taste bud were visualized with inherent fluorescence using Brainbow transgenic mice that were generated by mating the founder line L with nestin-cre mice. Multicolor fluorescence revealed perigemmal fibers as branched within the non-taste epithelium and ending in clusters of multiple rounded swellings surrounding the taste pore. Brainbow-labeling also revealed the morphology and branching pattern of single intragemmal fibers. These taste bud fibers frequently innervated both the peripheral bud, where immature gemmal cells are located, and the central bud, where mature, differentiated cells are located. The fibers typically bore preterminal and terminal swellings, growth cones with filopodia, swellings, and rounded retraction bulbs. These results establish an anatomical substrate for taste nerve fibers to contact and remodel among receptor cells at all stages of their differentiation, an interpretation that was supported by staining with GAP-43, a marker for growing fibers and growth cones. © 2016 Anatomical Society.

  3. Expression of Sex Steroid Hormone Receptors in Vagal Motor Neurons Innervating the Trachea and Esophagus in Mouse

    International Nuclear Information System (INIS)

    Mukudai, Shigeyuki; Ichi Matsuda, Ken; Bando, Hideki; Takanami, Keiko; Nishio, Takeshi; Sugiyama, Yoichiro; Hisa, Yasuo; Kawata, Mitsuhiro

    2016-01-01

    The medullary vagal motor nuclei, the nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMV), innervate the respiratory and gastrointestinal tracts. We conducted immunohistochemical analysis of expression of the androgen receptor (AR) and estrogen receptor α (ERα), in relation to innervation of the trachea and esophagus via vagal motor nuclei in mice. AR and ERα were expressed in the rostral NA and in part of the DMV. Tracing experiments using cholera toxin B subunit demonstrated that neurons of vagal motor nuclei that innervate the trachea and esophagus express AR and ERα. There was no difference in expression of sex steroid hormone receptors between trachea- and esophagus-innervating neurons. These results suggest that sex steroid hormones may act on vagal motor nuclei via their receptors, thereby regulating functions of the trachea and esophagus

  4. Innervation of the cow's inner ear derived from micro-computed tomography

    Science.gov (United States)

    Costeur, Loic; Mennecart, Bastien; Khimchenko, Anna; Müller, Bert; Schulz, Georg

    2017-09-01

    The innervation of the inner ear has been thoroughly investigated in humans and in some animal models such as the guinea pig, the rabbit, the cat, the dog, the rat, the pig and some monkeys. Ruminant inner ears are still poorly known and their innervation was never investigated despite its potential interest in phylogenetic reconstructions. Following earlier works on the ontogeny of the cow's ear, we expand our understanding of this structure by reconstructing the fine innervation pattern of the inner ear of the cow in two ontogenetic stages, at 7 months gestation and at an adult age. Since we work on dry skeletal specimens, only the endocast of the innervation inside the petrosal bone was reconstructed up to the internal acoustic meatus. The paths of the facial and vestibulocochlear nerves could be reconstructed together with that of the spiral ganglion canal. The nerves have a very fibrous pattern. The bony cavities of the ampular and utricular branches of the vestibulocochlear nerve could also be reconstructed. Our observations confirm that not all bony structures are present in foetal stages since the branch of cranial nerve VII is not visible on the foetus but very broad on the adult stage. The fibrous pattern within the modiolus connecting the spiral canal to the cochlear nerve is also less dense than in the adult stage. The shape of the branch of cranial nerve VII is very broad in the cow ending in a large hiatus Fallopii; this, together with the above-mentioned particularities, could constitute relevant observations for phylogenetical purposes when more data will be made available.

  5. The sympathetic and sensory innervation of rat airways: origin and neurochemical characterisation

    OpenAIRE

    Radtke, Anne

    2010-01-01

    Sensory and sympathetic innervation of Brown Norway rat airways were investigated using retrograde neuronal tracing with fluorescent dyes and double labelling immunofluorescence. Sensory neurons projecting to the lung are located in nodose and jugular vagal ganglia. Sympathetic neuronal supply of the lung originates in the stellate ganglia and superior cervical ganglia. Concerning immuno-reactivity for the SP and NOS in sensory and NPY and TH in sympathetic neurons were investigated. IR for S...

  6. Insulin resistance is associated with impaired cardiac sympathetic innervation in patients with heart failure.

    Science.gov (United States)

    Paolillo, S; Rengo, G; Pellegrino, T; Formisano, R; Pagano, G; Gargiulo, P; Savarese, G; Carotenuto, R; Petraglia, L; Rapacciuolo, A; Perrino, C; Piscitelli, S; Attena, E; Del Guercio, L; Leosco, D; Trimarco, B; Cuocolo, A; Perrone-Filardi, P

    2015-10-01

    Insulin resistance (IR) represents, at the same time, cause and consequence of heart failure (HF) and affects prognosis in HF patients, but pathophysiological mechanisms remain unclear. Hyperinsulinemia, which characterizes IR, enhances sympathetic drive, and it can be hypothesized that IR is associated with impaired cardiac sympathetic innervation in HF. Yet, this hypothesis has never been investigated. Aim of the present observational study was to assess the relationship between IR and cardiac sympathetic innervation in non-diabetic HF patients. One hundred and fifteen patients (87% males; 65 ± 11.3 years) with severe-to-moderate HF (ejection fraction 32.5 ± 9.1%) underwent iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy to assess sympathetic innervation and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) evaluation to determine the presence of IR. From (123)I-MIBG imaging, early and late heart to mediastinum (H/M) ratios and washout rate were calculated. Seventy-two (63%) patients showed IR and 43 (37%) were non-IR. Early [1.68 (IQR 1.53-1.85) vs. 1.79 (IQR 1.66-1.95); P = 0.05] and late H/M ratio [1.50 (IQR 1.35-1.69) vs. 1.65 (IQR 1.40-1.85); P = 0.020] were significantly reduced in IR compared with non-IR patients. Early and late H/M ratio showed significant inverse correlation with fasting insulinemia and HOMA-IR. Cardiac sympathetic innervation is more impaired in patients with IR and HF compared with matched non-IR patients. These findings shed light on the relationship among IR, HF, and cardiac sympathetic nervous system. Additional studies are needed to clarify the pathogenetic relationship between IR and HF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  7. Function and Innervation of the Locus Ceruleus in a Macaque Model of Functional Hypothalamic Amenorrhea

    OpenAIRE

    Bethea, Cynthia L; Kim, Aaron; Cameron, Judy L

    2012-01-01

    A body of knowledge implicates an increase in output from the locus ceruleus (LC) during stress. We questioned the innervation and function of the LC in our macaque model of Functional Hypothalamic Amenorrhea, also known as Stress-Induced Amenorrhea. Cohorts of macaques were initially characterized as highly stress resilient (HSR) or stress-sensitive (SS) based upon the presence or absence of ovulation during a protocol involving 2 menstrual cycles with psychosocial and metabolic stress. Afte...

  8. Distribution, Innervation, and Cellular Organization of Taste Buds in the Sea Catfish, Plotosus japonicus.

    Science.gov (United States)

    Nakamura, Tatsufumi; Matsuyama, Naoki; Kirino, Masato; Kasai, Masanori; Kiyohara, Sadao; Ikenaga, Takanori

    2017-01-01

    The gustatory system of the sea catfish Plotosus japonicus, like that of other catfishes, is highly developed. To clarify the details of the morphology of the peripheral gustatory system of Plotosus, we used whole-mount immunohistochemistry to investigate the distribution and innervation of the taste buds within multiple organs including the barbels, oropharyngeal cavity, fins (pectoral, dorsal, and caudal), and trunk. Labeled taste buds could be observed in all the organs examined. The density of the taste buds was higher along the leading edges of the barbels and fins; this likely increases the chance of detecting food. In all the fins, the taste buds were distributed in linear arrays parallel to the fin rays. Labeling of nerve fibers by anti-acetylated tubulin antibody showed that the taste buds within each sensory field are innervated in different ways. In the barbels, large nerve bundles run along the length of the organ, with fascicles branching off to innervate polygonally organized groups of taste buds. In the fins, nerve bundles run along the axis of fin rays to innervate taste buds lying in a line. In each case, small fascicles of fibers branch from large bundles and terminate within the basal portions of the taste buds. Serotonin immunohistochemistry demonstrated that most of the taste buds in all the organs examined contained disk-shaped serotonin-immunopositive cells in their basal region. This indicates a similar organization of the taste buds, in terms of the existence of serotonin-immunopositive basal cells, across the different sensory fields in this species. © 2017 S. Karger AG, Basel.

  9. Target innervation is necessary for neuronal polyploidization in the terrestrial slug Limax.

    Science.gov (United States)

    Matsuo, Ryota; Yamagishi, Miki; Wakiya, Kyoko; Tanaka, Yoko; Ito, Etsuro

    2013-08-01

    The brain of gastropod mollusks contains many giant neurons with polyploid genomic DNAs. Such DNAs are generated through repeated DNA endoreplication during body growth. However, it is not known what triggers DNA endoreplication in neurons. There are two possibilities: (1) DNAs are replicated in response to some unknown molecules in the hemolymph that reflect the nutritive status of the animal; or (2) DNAs are replicated in response to some unknown factors that are retrogradely transported through axons from the innervated target organs. We first tested whether hemolymph with rich nutrition could induce DNA endoreplication. We tested whether the transplanted brain exhibits enhanced DNA endoreplication like an endogenous brain does when transplanted into the homocoel of the body of a slug whose body growth is promoted by an increased food supply. However, no enhancement was observed in the frequency of DNA endoreplication when we compared the transplanted brains in the growth-promoted and growth-suppressed host slugs, suggesting that the humoral environment is irrelevant to triggering the body growth-dependent DNA endoreplication. Next, we tested the requirement of target innervation by surgically dissecting a unilateral posterior pedal nerve of an endogenous brain. Substantially lower number of neurons exhibited DNA endoreplication in the pedal ganglion ipsilateral to the dissected nerve. These results support the view that enhanced DNA endoreplication is mediated by target innervation and is not brought about through the direct effect of humoral factors in the hemolymph during body growth. Copyright © 2013 Wiley Periodicals, Inc.

  10. Sensory Innervation of the Nonspecialized Connective Tissues in the Low Back of the Rat

    Science.gov (United States)

    Corey, Sarah M.; Vizzard, Margaret A.; Badger, Gary J.; Langevin, Helene M.

    2011-01-01

    Chronic musculoskeletal pain, including low back pain, is a worldwide debilitating condition; however, the mechanisms that underlie its development remain poorly understood. Pathological neuroplastic changes in the sensory innervation of connective tissue may contribute to the development of nonspecific chronic low back pain. Progress in understanding such potentially important abnormalities is hampered by limited knowledge of connective tissue's normal sensory innervation. The goal of this study was to evaluate and quantify the sensory nerve fibers terminating within the nonspecialized connective tissues in the low back of the rat. With 3-dimensional reconstructions of thick (30–80 μm) tissue sections we have for the first time conclusively identified sensory nerve fiber terminations within the collagen matrix of connective tissue in the low back. Using dye labeling techniques with Fast Blue, presumptive dorsal root ganglia cells that innervate the low back were identified. Of the Fast Blue-labeled cells, 60–88% also expressed calcitonin gene-related peptide (CGRP) immunoreactivity. Based on the immunolabeling with CGRP and the approximate size of these nerve fibers (≤2 μm) we hypothesize that they are Aδ or C fibers and thus may play a role in the development of chronic pain. PMID:21411968

  11. Ontogeny of neuro-insular complexes and islets innervation in the human pancreas.

    Directory of Open Access Journals (Sweden)

    Alexandra E. Proshchina

    2014-04-01

    Full Text Available The ontogeny of the neuro-insular complexes (NIC and the islets innervation in human pancreas has not been studied in detail. Our aim was to describe the developmental dynamics and distribution of the nervous system structures in the endocrine part of human pancreas. We used doublestaining with antibodies specific to pan-neural markers (neuron-specific enolase (NSE and S100 protein and to hormones of pancreatic endocrine cells. NSE and S100-positive nerves and ganglia were identified in the human fetal pancreas from gestation week (gw 10 onwards. Later the density of S100 and NSE-positive fibers increased. In adults this network was sparse. The islets innervation started to form from gw 14. NSE-containing endocrine cells were identified from gw 12 onwards. Additionally, S100-positive cells were detected both in the periphery and within some of the islets starting at gw 14. The analysis of islets innervation has shown that the fetal pancreas contained neuro-insular complexes and the number of these complexes was reduced in adults. The highest density of neuro-insular complexes is detected during middle and late fetal periods, when the mosaic islets, typical for adults, form. The close integration between the developing pancreatic islets and the nervous system structures may play an important role not only in the hormone secretion, but also in the islets morphogenesis.

  12. Ontogeny of neuro-insular complexes and islets innervation in the human pancreas.

    Science.gov (United States)

    Proshchina, Alexandra E; Krivova, Yulia S; Barabanov, Valeriy M; Saveliev, Sergey V

    2014-01-01

    The ontogeny of the neuro-insular complexes (NIC) and the islets innervation in human pancreas has not been studied in detail. Our aim was to describe the developmental dynamics and distribution of the nervous system structures in the endocrine part of human pancreas. We used double-staining with antibodies specific to pan-neural markers [neuron-specific enolase (NSE) and S100 protein] and to hormones of pancreatic endocrine cells. NSE and S100-positive nerves and ganglia were identified in the human fetal pancreas from gestation week (gw) 10 onward. Later the density of S100 and NSE-positive fibers increased. In adults, this network was sparse. The islets innervation started to form from gw 14. NSE-containing endocrine cells were identified from gw 12 onward. Additionally, S100-positive cells were detected both in the periphery and within some of the islets starting at gw 14. The analysis of islets innervation has shown that the fetal pancreas contained NIC and the number of these complexes was reduced in adults. The highest density of NIC is detected during middle and late fetal periods, when the mosaic islets, typical for adults, form. The close integration between the developing pancreatic islets and the nervous system structures may play an important role not only in the hormone secretion, but also in the islets morphogenesis.

  13. Sensory and motor innervation of the crural diaphragm by the vagus nerves.

    Science.gov (United States)

    Young, Richard L; Page, Amanda J; Cooper, Nicole J; Frisby, Claudine L; Blackshaw, L Ashley

    2010-03-01

    During gastroesophageal reflux, transient lower esophageal sphincter relaxation and crural diaphragm (CD) inhibition occur concomitantly. Modifying vagus nerve control of transient lower esophageal sphincter relaxation is a major focus of development of therapeutics for gastroesophageal reflux disease, but neural mechanisms that coordinate the CD are poorly understood. Nerve tracing and immunolabeling were used to assess innervation of the diaphragm and lower esophageal sphincter in ferrets. Mechanosensory responses of vagal afferents in the CD and electromyography responses of the CD were recorded in novel in vitro preparations and in vivo. Retrograde tracing revealed a unique population of vagal CD sensory neurons in nodose ganglia and CD motor neurons in brainstem vagal nuclei. Anterograde tracing revealed specialized vagal endings in the CD and phrenoesophageal ligament-sites of vagal afferent mechanosensitivity recorded in vitro. Spontaneous electromyography activity persisted in the CD following bilateral phrenicotomy in vivo, while vagus nerve stimulation evoked electromyography responses in the CD in vitro and in vivo. We conclude that vagal sensory and motor neurons functionally innervate the CD and phrenoesophageal ligament. CD vagal afferents show mechanosensitivity to distortion of the gastroesophageal junction, while vagal motor neurons innervate both CD and distal esophagus and may represent a common substrate for motor control of the reflux barrier. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Estrogen Replacement Regulates Vaginal Innervations in Ovariectomized Adult Virgin Rats: A Histological Study

    Directory of Open Access Journals (Sweden)

    Ting Li

    2017-01-01

    Full Text Available Background. Our previous Gräfenberg spot findings confirmed that the distal-third areas of the anterior vaginal wall bore a significantly greater number of nerves and sexual hormone may have certain degree of influence on these significant differences. However, the role of estrogen in vaginal innervations remains controversial. Methods. To investigate whether hormonal-neural interactions occur in the vagina, sixty rats were randomly divided into six groups: Sham-operated, ovariectomy, and 4 treatment groups. After 2 weeks of treatment, vaginal biopsies were prepared with hematoxylin and eosin and PGP9.5 using immunohistochemistry. Results. The density of small nerve fibers was significantly higher in the distal-half areas of intact vaginal walls than the proximal-half areas (P=0.001. In contrast, the overall PGP 9.5-ir fiber innervation density was significantly decreased in the OVX rats subjected to surgical menopause. Sustained estrogen administration for 2 weeks resulted in nerve fiber proliferation, with values reaching normal levels in the low-dose estradiol valerate group. Conclusion. Our findings indicate that systemic hormonal therapy with low-dose estradiol valerate is effective and safe for treating deficient vaginal innervation caused by low level of estrogen activity in menopausal women and may aid studies to identify an optimal estradiol dose to provide relief from vaginal discomfort.

  15. Oropharyngeal and laryngeal sensory innervation in the pathophysiology of swallowing disorders and sensory stimulation treatments.

    Science.gov (United States)

    Alvarez-Berdugo, Daniel; Rofes, Laia; Casamitjana, J Francesc; Padrón, Andreína; Quer, Miquel; Clavé, Pere

    2016-09-01

    Oropharyngeal dysphagia (OD) affects older and neurological patients, causing malnutrition and dehydration and increasing the risk for aspiration pneumonia. There is evidence that sensory deficits in those populations are closely related to swallowing disorders, and several research groups are developing new therapies based on sensory stimulation of this area. More information on the sensory innervation participating in the swallow response is needed to better understand the pathophysiology of OD and to develop new treatments. This review focuses on the sensory innervation of the human oropharynx and larynx in healthy people compared with patients with swallowing disorders in order to unravel the abnormalities that may lead to the loss of sensitivity in patients with OD. We also hypothesize the pathway through which active sensory-enhancement treatments may elicit their therapeutic effect on patients with swallowing dysfunctions. As far as we know, this is the first time a review covers the anatomy, histology, ultrastructure, and molecular biology of the sensory innervation of the swallowing function. © 2016 New York Academy of Sciences.

  16. Heterogeneous sensory innervation and extensive intrabulbar connections of olfactory necklace glomeruli.

    Directory of Open Access Journals (Sweden)

    Renee E Cockerham

    Full Text Available The mammalian nose employs several olfactory subsystems to recognize and transduce diverse chemosensory stimuli. These subsystems differ in their anatomical position within the nasal cavity, their targets in the olfactory forebrain, and the transduction mechanisms they employ. Here we report that they can also differ in the strategies they use for stimulus coding. Necklace glomeruli are the sole main olfactory bulb (MOB targets of an olfactory sensory neuron (OSN subpopulation distinguished by its expression of the receptor guanylyl cyclase GC-D and the phosphodiesterase PDE2, and by its chemosensitivity to the natriuretic peptides uroguanylin and guanylin and the gas CO(2. In stark contrast to the homogeneous sensory innervation of canonical MOB glomeruli from OSNs expressing the same odorant receptor (OR, we find that each necklace glomerulus of the mouse receives heterogeneous innervation from at least two distinct sensory neuron populations: one expressing GC-D and PDE2, the other expressing olfactory marker protein. In the main olfactory system it is thought that odor identity is encoded by a combinatorial strategy and represented in the MOB by a pattern of glomerular activation. This combinatorial coding scheme requires functionally homogeneous sensory inputs to individual glomeruli by OSNs expressing the same OR and displaying uniform stimulus selectivity; thus, activity in each glomerulus reflects the stimulation of a single OSN type. The heterogeneous sensory innervation of individual necklace glomeruli by multiple, functionally distinct, OSN subtypes precludes a similar combinatorial coding strategy in this olfactory subsystem.

  17. Midbrain dopamine neurons associated with reward processing innervate the neurogenic subventricular zone.

    Science.gov (United States)

    Lennington, Jessica B; Pope, Sara; Goodheart, Anna E; Drozdowicz, Linda; Daniels, Stephen B; Salamone, John D; Conover, Joanne C

    2011-09-14

    Coordinated regulation of the adult neurogenic subventricular zone (SVZ) is accomplished by a myriad of intrinsic and extrinsic factors. The neurotransmitter dopamine is one regulatory molecule implicated in SVZ function. Nigrostriatal and ventral tegmental area (VTA) midbrain dopamine neurons innervate regions adjacent to the SVZ, and dopamine synapses are found on SVZ cells. Cell division within the SVZ is decreased in humans with Parkinson's disease and in animal models of Parkinson's disease following exposure to toxins that selectively remove nigrostriatal neurons, suggesting that dopamine is critical for SVZ function and nigrostriatal neurons are the main suppliers of SVZ dopamine. However, when we examined the aphakia mouse, which is deficient in nigrostriatal neurons, we found no detrimental effect to SVZ proliferation or organization. Instead, dopamine innervation of the SVZ tracked to neurons at the ventrolateral boundary of the VTA. This same dopaminergic neuron population also innervated the SVZ of control mice. Characterization of these neurons revealed expression of proteins indicative of VTA neurons. Furthermore, exposure to the neurotoxin MPTP depleted neurons in the ventrolateral VTA and resulted in decreased SVZ proliferation. Together, these results reveal that dopamine signaling in the SVZ originates from a population of midbrain neurons more typically associated with motivational and reward processing.

  18. Vagal innervation is required for pulmonary function phenotype in Htr4-/- mice.

    Science.gov (United States)

    House, John S; Nichols, Cody E; Li, Huiling; Brandenberger, Christina; Virgincar, Rohan S; DeGraff, Laura M; Driehuys, Bastiaan; Zeldin, Darryl C; London, Stephanie J

    2017-04-01

    Human genome-wide association studies have identified over 50 loci associated with pulmonary function and related phenotypes, yet follow-up studies to determine causal genes or variants are rare. Single nucleotide polymorphisms in serotonin receptor 4 ( HTR4 ) are associated with human pulmonary function in genome-wide association studies and follow-up animal work has demonstrated that Htr4 is causally associated with pulmonary function in mice, although the precise mechanisms were not identified. We sought to elucidate the role of neural innervation and pulmonary architecture in the lung phenotype of Htr4 -/- animals. We report here that the Htr4 -/- phenotype in mouse is dependent on vagal innervation to the lung. Both ex vivo tracheal ring reactivity and in vivo flexiVent pulmonary functional analyses demonstrate that vagotomy abrogates the Htr4 -/- airway hyperresponsiveness phenotype. Hyperpolarized 3 He gas magnetic resonance imaging and stereological assessment of wild-type and Htr4 -/- mice reveal no observable differences in lung volume, inflation characteristics, or pulmonary microarchitecture. Finally, control of breathing experiments reveal substantive differences in baseline breathing characteristics between mice with/without functional HTR4 in breathing frequency, relaxation time, flow rate, minute volume, time of inspiration and expiration and breathing pauses. These results suggest that HTR4's role in pulmonary function likely relates to neural innervation and control of breathing. Copyright © 2017 the American Physiological Society.

  19. [Efferent innervation of the arteries of human leptomeninx in arterial hypertension].

    Science.gov (United States)

    Chertok, V M; Kotsiuba, A E; Babich, E V

    2009-01-01

    Structure of the efferent nerve plexuses (adrenergic, acetylcholinestherase- and cholinacetyltranspherase-positive, NO-dependent), was studied in the arteries of human leptomeninx with different diameters. Material was obtained from the corpses of the healthy people and of the patients with initial stages of arterial hypertension (AH). It was shown that the concentrations of cholinergic and adrenergic nerve fibers and varicosities in axon terminal part, innervating the arteries with the diameters ranging from 450 till 100 microm, were not significantly different. In these arteries, NO-ergic plexuses were also detected. In patients with AH, regardless the arterial diameters, the significant increase (up to 15-20%) of adrenergic nerve fiber and varicosity concentrations was found. The changes in cholinergic nerve fiber concentration were found to depend on the vessel diameter: the significant decrease of these parameter was observed only in arteries with the diameter of 100-200 microm. No significant changes in nerve plexus concentration was noticed in the arteries with greater or smaller diameter. In NO-ergic neural conductors, the enzyme activity decreased only in the large arteries, and remained almost unchanged in the small vascular branches. The changes in the vasomotor innervation described in AH, are interpreted as a vasomotor innervation dysfunction of the leptomeninx arteries that may result in the hemodynamic disturbances.

  20. Polarity in Mammalian Epithelial Morphogenesis

    OpenAIRE

    Roignot, Julie; Peng, Xiao; Mostov, Keith

    2013-01-01

    Cell polarity is fundamental for the architecture and function of epithelial tissues. Epithelial polarization requires the intervention of several fundamental cell processes, whose integration in space and time is only starting to be elucidated. To understand what governs the building of epithelial tissues during development, it is essential to consider the polarization process in the context of the whole tissue. To this end, the development of three-dimensional organotypic cell culture model...

  1. Peripheral epithelial odontogenic tumor

    International Nuclear Information System (INIS)

    Carzoglio, J.; Tancredi, N.; Capurro, S.; Ravecca, T.; Scarrone, P.

    2006-01-01

    A new case of peripheral epithelial odontogenic tumor (Pindborg tumor) is reported. It is localized in the superior right gingival region, a less frequent site, and has the histopathological features previously reported. Immunochemical studies were performed, revealing a differential positive stain to cytokeratins in tumor cells deeply seated in the tumor mass, probably related to tumoral cell heterogeneity.Interestingly, in this particular case S-100 protein positive reactivity was also detected in arborescent cells intermingled with tumoral cells, resembling Langerhans cells. Even though referred in the literature in central Pindborg tumors, no references were found about their presence in peripheral tumors, like the one that is presented here

  2. Human corneal epithelial subpopulations

    DEFF Research Database (Denmark)

    Søndergaard, Chris Bath

    2013-01-01

    Corneal epithelium is being regenerated throughout life by limbal epithelial stem cells (LESCs) believed to be located in histologically defined stem cell niches in corneal limbus. Defective or dysfunctional LESCs result in limbal stem cell deficiency (LSCD) causing pain and decreased visual acuity...... subpopulations in human corneal epithelium using a combination of laser capture microdissection and RNA sequencing for global transcriptomic profiling. We compared dissociation cultures, using either expansion on γ-irradiated NIH/3T3 feeder cells in serum-rich medium or expansion directly on plastic in serum...

  3. Epithelial Cell Cultures

    Directory of Open Access Journals (Sweden)

    Imran S. Chaudhry

    2011-01-01

    Full Text Available The biological effects of only a finite number of tobacco toxins have been studied. Here, we describe exposure of cultures of human bronchial epithelial cells to low concentrations of tobacco carcinogens: nickel sulphate, benzo(bfluoranthene, N-nitrosodiethylamine, and 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK. After a 24-hour exposure, EGFR was expressed in cell membrane and cytoplasm, BCL-2 was expressed only in the irregular nuclei of large atypical cells, MKI67 was expressed in nuclei with no staining in larger cells, cytoplasmic BIRC5 with stronger nuclear staining was seen in large atypical cells, and nuclear TP53 was strongly expressed in all cells. After only a 24-hour exposure, cells exhibited atypical nuclear and cytoplasmic features. After a 48-hour exposure, EGFR staining was localized to the nucleus, BCL-2 was slightly decreased in intensity, BIRC5 was localized to the cytoplasm, and TP53 staining was increased in small and large cells. BCL2L1 was expressed in both the cytoplasm and nuclei of cells at 24- and 48-hour exposures. We illustrate that short-termexposure of a bronchial epithelial cell line to smoking-equivalent concentrations of tobacco carcinogens alters the expression of key proliferation regulatory genes, EGFR, BCL-2, BCL2L1, BIRC5, TP53, and MKI67, similar to that reported in biopsy specimens of pulmonary epithelium described to be preneoplastic lesions.

  4. Macroscopic Innervation of the Dura Mater Covering the Middle Cranial Fossa in Humans Correlated to Neurovascular Headache.

    Science.gov (United States)

    Lee, Shin-Hyo; Hwang, Seung-Jun; Koh, Ki-Seok; Song, Wu-Chul; Han, Sang-Don

    2017-01-01

    The trigeminovascular system within the cranial dura mater is a possible cause of headaches. The aim of this study is to investigate macroscopically dural innervation around the middle meningeal artery (MMA) in the middle cranial fossa. Forty-four sides of the cranial dura overlying the skull base obtained from 24 human cadavers were stained using Sihler's method. Overall, the nervus spinosus (NS) from either the maxillary or mandibular trigeminal divisions ran along the lateral wall of the middle meningeal vein rather than that of the MMA. Distinct bundles of the NS running along the course of the frontal branches of the MMA were present in 81.8% of cases ( N = 36). Others did not form dominant nerve bundles, instead giving off free nerve endings along the course of the MMA or dural connective tissue. The distribution of these nerve endings was similar to that of the course of the frontal, parietal and petrosal branches of the MMA (11.4%). The others were not restricted to a perivascular plexus, crossing the dural connective tissues far from the MMA (6.8%). These findings indicate that the NS generally travels alongside the course of the frontal branches of the MMA and terminates in the vicinity of the pterion.

  5. Macroscopic Innervation of the Dura Mater Covering the Middle Cranial Fossa in Humans Correlated to Neurovascular Headache

    Directory of Open Access Journals (Sweden)

    Shin-Hyo Lee

    2017-12-01

    Full Text Available The trigeminovascular system within the cranial dura mater is a possible cause of headaches. The aim of this study is to investigate macroscopically dural innervation around the middle meningeal artery (MMA in the middle cranial fossa. Forty-four sides of the cranial dura overlying the skull base obtained from 24 human cadavers were stained using Sihler’s method. Overall, the nervus spinosus (NS from either the maxillary or mandibular trigeminal divisions ran along the lateral wall of the middle meningeal vein rather than that of the MMA. Distinct bundles of the NS running along the course of the frontal branches of the MMA were present in 81.8% of cases (N = 36. Others did not form dominant nerve bundles, instead giving off free nerve endings along the course of the MMA or dural connective tissue. The distribution of these nerve endings was similar to that of the course of the frontal, parietal and petrosal branches of the MMA (11.4%. The others were not restricted to a perivascular plexus, crossing the dural connective tissues far from the MMA (6.8%. These findings indicate that the NS generally travels alongside the course of the frontal branches of the MMA and terminates in the vicinity of the pterion.

  6. The world of epithelial sheets.

    Science.gov (United States)

    Honda, Hisao

    2017-06-01

    An epithelium is a layer of closely connected cells covering the body or lining a body cavity. In this review, several fundamental questions are addressed regarding the epithelium. (i) While an epithelium functions as barrier against the external environment, how is barrier function maintained during its construction? (ii) What determines the apical and basal sides of epithelial layer? (iii) Is there any relationship between the apical side of the epithelium and the apical membrane of an epithelial cell? (iv) Why are hepatocytes (liver cells) called epithelial, even though they differ completely from column-like shape of typical epithelial cells? Keeping these questions in mind, multiple shapes of epithelia were considered, extracting a few of their elemental processes, and constructing a virtual world of epithelia by combining them. Epithelial cells were also classified into several types based on the number of apical domains of each cell. In addition, an intracellular organelle was introduced within epithelial cells, the vacuolar apical compartment (VAC), which is produced within epithelial cells surrounded by external cell matrix (ECM). The VAC interacts with areas of cell-cell contact of the cell surface membrane and is converted to apical membrane. The properties of VACs enable us to answer the initial questions posed above. Finally, the genetic and molecular mechanisms of epithelial morphogenesis are discussed. © 2017 Japanese Society of Developmental Biologists.

  7. Targeted taste cell-specific overexpression of brain-derived neurotrophic factor in adult taste buds elevates phosphorylated TrkB protein levels in taste cells, increases taste bud size, and promotes gustatory innervation.

    Science.gov (United States)

    Nosrat, Irina V; Margolskee, Robert F; Nosrat, Christopher A

    2012-05-11

    Brain-derived neurotrophic factor (BDNF) is the most potent neurotrophic factor in the peripheral taste system during embryonic development. It is also expressed in adult taste buds. There is a lack of understanding of the role of BDNF in the adult taste system. To address this, we generated novel transgenic mice in which transgene expression was driven by an α-gustducin promoter coupling BDNF expression to the postnatal expression of gustducin in taste cells. Immunohistochemistry revealed significantly stronger BDNF labeling in taste cells of high BDNF-expressing mouse lines compared with controls. We show that taste buds in these mice are significantly larger and have a larger number of taste cells compared with controls. To examine whether innervation was affected in Gust-BDNF mice, we used antibodies to neural cell adhesion molecule (NCAM) and ATP receptor P2X3. The total density of general innervation and specifically the gustatory innervation was markedly increased in high BDNF-expressing mice compared with controls. TrkB and NCAM gene expression in laser capture microdissected taste epithelia were significantly up-regulated in these mice. Up-regulation of TrkB transcripts in taste buds and elevated taste cell-specific TrkB phosphorylation in response to increased BDNF levels indicate that BDNF controls the expression and activation of its high affinity receptor in taste cells. This demonstrates a direct taste cell function for BDNF. BDNF also orchestrates and maintains taste bud innervation. We propose that the Gust-BDNF transgenic mouse models can be employed to further dissect the specific roles of BDNF in the adult taste system.

  8. Targeted Taste Cell-specific Overexpression of Brain-derived Neurotrophic Factor in Adult Taste Buds Elevates Phosphorylated TrkB Protein Levels in Taste Cells, Increases Taste Bud Size, and Promotes Gustatory Innervation*

    Science.gov (United States)

    Nosrat, Irina V.; Margolskee, Robert F.; Nosrat, Christopher A.

    2012-01-01

    Brain-derived neurotrophic factor (BDNF) is the most potent neurotrophic factor in the peripheral taste system during embryonic development. It is also expressed in adult taste buds. There is a lack of understanding of the role of BDNF in the adult taste system. To address this, we generated novel transgenic mice in which transgene expression was driven by an α-gustducin promoter coupling BDNF expression to the postnatal expression of gustducin in taste cells. Immunohistochemistry revealed significantly stronger BDNF labeling in taste cells of high BDNF-expressing mouse lines compared with controls. We show that taste buds in these mice are significantly larger and have a larger number of taste cells compared with controls. To examine whether innervation was affected in Gust-BDNF mice, we used antibodies to neural cell adhesion molecule (NCAM) and ATP receptor P2X3. The total density of general innervation and specifically the gustatory innervation was markedly increased in high BDNF-expressing mice compared with controls. TrkB and NCAM gene expression in laser capture microdissected taste epithelia were significantly up-regulated in these mice. Up-regulation of TrkB transcripts in taste buds and elevated taste cell-specific TrkB phosphorylation in response to increased BDNF levels indicate that BDNF controls the expression and activation of its high affinity receptor in taste cells. This demonstrates a direct taste cell function for BDNF. BDNF also orchestrates and maintains taste bud innervation. We propose that the Gust-BDNF transgenic mouse models can be employed to further dissect the specific roles of BDNF in the adult taste system. PMID:22442142

  9. Taste bud-derived BDNF maintains innervation of a subset of TrkB-expressing gustatory nerve fibers.

    Science.gov (United States)

    Tang, Tao; Rios-Pilier, Jennifer; Krimm, Robin

    2017-07-01

    Taste receptor cells transduce different types of taste stimuli and transmit this information to gustatory neurons that carry it to the brain. Taste receptor cells turn over continuously in adulthood, requiring constant new innervation from nerve fibers. Therefore, the maintenance of innervation to taste buds is an active process mediated by many factors, including brain-derived neurotrophic factor (BDNF). Specifically, 40% of taste bud innervation is lost when Bdnf is removed during adulthood. Here we speculated that not all gustatory nerve fibers express the BDNF receptor, TrkB, resulting in subsets of neurons that vary in their response to BDNF. However, it is also possible that the partial loss of innervation occurred because the Bdnf gene was not effectively removed. To test these possibilities, we first determined that not all gustatory nerve fibers express the TrkB receptor in adult mice. We then verified the efficiency of Bdnf removal specifically in taste buds of K14-CreER:Bdnf mice and found that Bdnf expression was reduced to 1%, indicating efficient Bdnf gene recombination. BDNF removal resulted in a 55% loss of TrkB-expressing nerve fibers, which was greater than the loss of P2X3-positive fibers (39%), likely because taste buds were innervated by P2X3+/TrkB- fibers that were unaffected by BDNF removal. We conclude that gustatory innervation consists of both TrkB-positive and TrkB-negative taste fibers and that BDNF is specifically important for maintaining TrkB-positive innervation to taste buds. In addition, although taste bud size was not affected by inducible Bdnf removal, the expression of the γ subunit of the ENaC channel was reduced. So, BDNF may regulate expression of some molecular components of taste transduction pathways. Copyright © 2017. Published by Elsevier Inc.

  10. Adrenal hormones interact with sympathetic innervation to modulate growth of embryonic heart in oculo.

    Science.gov (United States)

    Tucker, D C; Torres, A

    1992-02-01

    To allow experimental manipulation of adrenal hormone and autonomic influences on developing myocardium without alteration of hemodynamic load, embryonic rat heart was cultured in the anterior eye chamber of an adult rat. Sympathetic innervation of embryonic day 12 heart grafts was manipulated by surgical sympathectomy of one eye chamber in each host rat. Adrenal hormone exposure was manipulated by host adrenal medullectomy (MEDX) in experiment 1 and by host adrenalectomy (ADX) in experiment 2. In experiment 1, whole heart grafts were larger in MEDX than in sham-operated hosts by 8 wk in oculo (6.14 +/- 0.71 vs. 5.09 +/- 0.69 mm2 with innervation intact and 7.97 +/- 2.07 vs. 3.09 +/- 0.63 mm2 with sympathetic innervation prevented). In experiment 2, host ADX increased growth of embryonic day 12 ventricles grafted into sympathectomized eye chambers (0.69 +/- 0.10 vs. 0.44 +/- 0.04 mm2) but did not affect growth of grafts in intact eye chambers (0.85 +/- 0.09 vs. 1.05 +/- 0.15 mm2). Corticosterone replacement (4 mg/day) entirely reversed the effect of host ADX on graft growth (superior cervical ganglionectomy, 0.47 +/- 0.03 mm2; intact eye chambers, 0.90 +/- 0.91 mm2). Beating rate of grafts was not affected by adrenal hormone manipulations. These experiments indicate that the compromised growth of embryonic heart grafts placed in sympathectomized eye chambers requires exposure to adult levels of glucocorticoids during the early days after grafting. These results suggest that interactions between neural and hormonal stimulation influence cardiac growth in the in oculo culture system and during normal development.

  11. Splenic epithelial cyst

    International Nuclear Information System (INIS)

    Yousuf, M.; Jalali, U.

    2011-01-01

    Cysts of spleen are rare entities. Congenital splenic cysts are even more uncommon comprising of only 10% of benign non-parasitic cysts. We report a case of 22 years old female who presented with history of 2 years abdominal pain and gradual distension. Ultrasound and computed tomography (CT) both were suggestive of splenic cyst. Laboratory tests show thrombocytopenia with platelets count of 97000 per cubic millimeter and anemia with hemoglobin 8.7 gram per deciliter. Serological tests were negative for parasitic infection. Splenectomy was done and the weight of the spleen was found to be 1.5 kilogram. Histopathological findings are consistent with splenic epithelial cyst. The aetiology, diagnostic modalities and treatment options are discussed in the case report. (author)

  12. Development of cardiac parasympathetic neurons, glial cells, and regional cholinergic innervation of the mouse heart.

    Science.gov (United States)

    Fregoso, S P; Hoover, D B

    2012-09-27

    Very little is known about the development of cardiac parasympathetic ganglia and cholinergic innervation of the mouse heart. Accordingly, we evaluated the growth of cholinergic neurons and nerve fibers in mouse hearts from embryonic day 18.5 (E18.5) through postnatal day 21(P21). Cholinergic perikarya and varicose nerve fibers were identified in paraffin sections immunostained for the vesicular acetylcholine transporter (VAChT). Satellite cells and Schwann cells in adjacent sections were identified by immunostaining for S100β calcium binding protein (S100) and brain-fatty acid binding protein (B-FABP). We found that cardiac ganglia had formed in close association to the atria and cholinergic innervation of the atrioventricular junction had already begun by E18.5. However, most cholinergic innervation of the heart, including the sinoatrial node, developed postnatally (P0.5-P21) along with a doubling of the cross-sectional area of cholinergic perikarya. Satellite cells were present throughout neonatal cardiac ganglia and expressed primarily B-FABP. As they became more mature at P21, satellite cells stained strongly for both B-FABP and S100. Satellite cells appeared to surround most cardiac parasympathetic neurons, even in neonatal hearts. Mature Schwann cells, identified by morphology and strong staining for S100, were already present at E18.5 in atrial regions that receive cholinergic innervation at later developmental times. The abundance and distribution of S100-positive Schwann cells increased postnatally along with nerve density. While S100 staining of cardiac Schwann cells was maintained in P21 and older mice, Schwann cells did not show B-FABP staining at these times. Parallel development of satellite cells and cholinergic perikarya in the cardiac ganglia and the increase in abundance of Schwann cells and varicose cholinergic nerve fibers in the atria suggest that neuronal-glial interactions could be important for development of the parasympathetic nervous

  13. Management of pain in autosomal dominant polycystic kidney disease and anatomy of renal innervation.

    Science.gov (United States)

    Tellman, Matthew W; Bahler, Clinton D; Shumate, Ashley M; Bacallao, Robert L; Sundaram, Chandru P

    2015-05-01

    Chronic pain is a prominent feature of autosomal dominant polycystic kidney disease that is difficult to treat and manage, often resulting in a decrease in quality of life. Understanding the underlying anatomy of renal innervation and the various etiologies of pain that occur in autosomal dominant polycystic kidney disease can help guide proper treatments to manage pain. Reviewing previously studied treatments for pain in autosomal dominant polycystic kidney disease can help characterize treatment in a stepwise fashion. We performed a literature search of the etiology and management of pain in autosomal dominant polycystic kidney disease and the anatomy of renal innervation using PubMed® and Embase® from January 1985 to April 2014 with limitations to human studies and English language. Pain occurs in the majority of patients with autosomal dominant polycystic kidney disease due to renal, hepatic and mechanical origins. Patients may experience different types of pain which can make it difficult to clinically confirm its etiology. An anatomical and histological evaluation of the complex renal innervation helps in understanding the mechanisms that can lead to renal pain. Understanding the complex nature of renal innervation is essential for surgeons to perform renal denervation. The management of pain in autosomal dominant polycystic kidney disease should be approached in a stepwise fashion. Acute causes of renal pain must first be ruled out due to the high incidence in autosomal dominant polycystic kidney disease. For chronic pain, nonopioid analgesics and conservative interventions can be used first, before opioid analgesics are considered. If pain continues there are surgical interventions such as renal cyst decortication, renal denervation and nephrectomy that can target pain produced by renal or hepatic cysts. Chronic pain in patients with autosomal dominant polycystic kidney disease is often refractory to conservative, medical and other noninvasive treatments

  14. Phalloplasty with an Innervated Island Pedicled Anterolateral Thigh Flap in a Female-to-Male Transsexual

    OpenAIRE

    Hasegawa, Kenjiro; Namba, Yuzaburo; Kimata, Yoshihiro

    2013-01-01

    Since 2001, we have been performing phalloplasty with a radial forearm free flap as the flap of first choice in female-to-male transsexuals (FTMTS). In the present case, a 22-year-old FTMTS with a negative Allen test, we achieved good results by performing phalloplasty with an innervated island pedicled anterolateral thigh flap using the "tube within a tube" technique, in which the penis and urethra are constructed with a single flap. While phalloplasty with an island-pedicled or free anterol...

  15. Innervation of periesophageal region of cat's diaphragm - Implication for studies of control of vomiting

    Science.gov (United States)

    Tan, L. K.; Miller, A. D.

    1986-01-01

    The extent of the region of the diaphragm around the esophagus that displays greatly reduced activity during the expulsive phase of vomiting was determined from electromyographic studies in cats to be about 0.75-1.0 cm from the esophagus. Horseradish peroxidase injected into this region retrogradely labeled motoneurons throughout most of the rostral-caudal extent of the phrenic nucleus, with the exception of caudal C6 and rostral C7. This widespread intermingling of motoneurons that innervate the region of reduced activity with other phrenic motoneurons creates a difficulty for needed follow-up studies of diaphragmatic control during vomiting.

  16. Sensory innervation of the dorsal longitudinal ligament and the meninges in the lumbar spine of the dog.

    Science.gov (United States)

    Waber-Wenger, Barbara; Forterre, Franck; Kuehni-Boghenbor, Kathrin; Danuser, Renzo; Stein, Jens Volker; Stoffel, Michael Hubert

    2014-10-01

    Although intervertebral disc herniation is a well-known disease in dogs, pain management for this condition has remained a challenge. The goal of the present study is to address the lack of information regarding the innervation of anatomical structures within the canine vertebral canal. Immunolabeling was performed with antibodies against protein gene product 9.5, Tuj-1 (neuron-specific class III β-tubulin), calcitonin gene-related peptide, and neuropeptide Y in combination with the lectin from Lycopersicon esculentum as a marker for blood vessels. Staining was indicative of both sensory and sympathetic fibers. Innervation density was the highest in lateral areas, intermediate in dorsal areas, and the lowest in ventral areas. In the dorsal longitudinal ligament (DLL), the highest innervation density was observed in the lateral regions. Innervation was lower at mid-vertebral levels than at intervertebral levels. The presence of sensory and sympathetic fibers in the canine dura and DLL suggests that pain may originate from both these structures. Due to these regional differences in sensory innervation patterns, trauma to intervertebral DLL and lateral dura is expected to be particularly painful. The results ought to provide a better basis for the assessment of medicinal and surgical procedures.

  17. Replication of cultured lung epithelial cells

    International Nuclear Information System (INIS)

    Guzowski, D.; Bienkowski, R.

    1986-01-01

    The authors have investigated the conditions necessary to support replication of lung type 2 epithelial cells in culture. Cells were isolated from mature fetal rabbit lungs (29d gestation) and cultured on feeder layers of mitotically inactivated 3T3 fibroblasts. The epithelial nature of the cells was demonstrated by indirect immunofluorescent staining for keratin and by polyacid dichrome stain. Ultrastructural examination during the first week showed that the cells contained myofilaments, microvilli and lamellar bodies (markers for type 2 cells). The following changes were observed after the first week: increase in cell size; loss of lamellar bodies and appearance of multivesicular bodies; increase in rough endoplasmic reticulum and golgi; increase in tonafilaments and well-defined junctions. General cell morphology was good for up to 10 wk. Cells cultured on plastic surface degenerated after 1 wk. Cell replication was assayed by autoradiography of cultures exposed to ( 3 H)-thymidine and by direct cell counts. The cells did not replicate during the first week; however, between 2-10 wk the cells incorporated the label and went through approximately 6 population doublings. They have demonstrated that lung alveolar epithelial cells can replicate in culture if they are maintained on an appropriate substrate. The coincidence of ability to replicate and loss of markers for differentiation may reflect the dichotomy between growth and differentiation commonly observed in developing systems

  18. Modulation of epithelial sodium channel in human alveolar epithelial ...

    African Journals Online (AJOL)

    Modulation of epithelial sodium channel in human alveolar epithelial cells by lipoxin A4 through AhR-cAMP-dependent pathway. Bi-Huan Cheng1,2, Li-Wei Pan2, Sheng-Rong Zhang3, Bin-Yu Ying2, Ben-Ji. Wang2, Guo-Liang Lin2 and Shi-Fang Ding1*. 1Department of Critical Care Medicine, Qilu Hospital of Shandong ...

  19. EVOLUTION OF NEUROENDOCRINE CELL POPULATION AND PEPTIDERGIC INNERVATION, ASSESSED BY DISCRIMINANT ANALYSIS, DURING POSTNATAL DEVELOPMENT OF THE RAT PROSTATE

    Directory of Open Access Journals (Sweden)

    Rosario Rodríguez

    2011-05-01

    Full Text Available Serotonin immunoreactive neuroendocrine cells and peptidergic nerves (NPY and VIP could have a role in prostate growth and function. In the present study, rats grouped by stages of postnatal development (prepubertal, pubertal, young and aged adults were employed in order to ascertain whether age causes changes in the number of serotoninergic neuroendocrine cells and the length of NPY and VIP fibres. Discriminant analysis was performed in order to ascertain the classificatory power of stereologic variables (absolute and relative measurements of cell number and fibre length on age groups. The following conclusions were drawn: a discriminant analysis confirms the androgen-dependence of both neuroendocrine cells and NPYVIP innervation during the postnatal development of the rat prostate; b periglandular innervation has more relevance than interglandular innervation in classifying the rats in age groups; and c peptidergic nerves from ventral, ampullar and periductal regions were more age-dependent than nerves from the dorso-lateral region.

  20. Influence of psychomotor skills and innervation patterns on results of latissimus dorsi tendon transfer for irreparable rotator cuff tears.

    Science.gov (United States)

    Werner, Clément M L; Ruckstuhl, Thomas; Müller, Roland; Zanetti, Marco; Gerber, Christian

    2008-01-01

    This investigation was performed to analyze the influence of innervation and psychomotor skills on the outcome of latissimus dorsi transfer. Patients with the 10 best and 10 worst results after latissimus dorsi transfer for irreparable rotator cuff tears were selected. All patients meeting the inclusion criteria (n = 12) were subject to a psychomotor test battery (Motorische Leistungsserie) and electromyographic innervation assessment. There was no statistical difference between the 2 groups preoperatively in terms of the commonly tested factors known to influence the results of this procedure adversely. There was a significant difference in both the pattern and selectivity of innervation in the group that had better clinical results. The psychomotor findings were negatively correlated with the range of motion and the strength of the operative shoulder. Function of the operative shoulder could also be predicted by psychomotor function of the uninjured contralateral side. Psychomotor skills testing appears to be a new, potential method by which to predict the outcome of latissimus dorsi transfer.

  1. Heart Development, Diseases, and Regeneration - New Approaches From Innervation, Fibroblasts, and Reprogramming.

    Science.gov (United States)

    Ieda, Masaki

    2016-09-23

    It is well known that cardiac function is tightly controlled by neural activity; however, the molecular mechanism of cardiac innervation during development and the relationship with heart disease remain undetermined. My work has revealed the molecular networks that govern cardiac innervation and its critical roles in heart diseases such as silent myocardial ischemia and arrhythmias. Cardiomyocytes proliferate during embryonic development, but lose their proliferative capacity after birth. Cardiac fibroblasts are a major source of cells during fibrosis and induce cardiac hypertrophy after myocardial injury in the adult heart. Despite the importance of fibroblasts in the adult heart, the role of fibroblasts in embryonic heart development was previously not determined. I demonstrated that cardiac fibroblasts play important roles in myocardial growth and cardiomyocyte proliferation during embryonic development, and I identified key paracrine factors and signaling pathways. In contrast to embryonic cardiomyocytes, adult cardiomyocytes have little regenerative capacity, leading to heart failure and high mortality rates after myocardial infarction. Leveraging the knowledge of developmental biology, I identified cardiac reprogramming factors that can directly convert resident cardiac fibroblasts into cardiomyocytes for heart regeneration. These findings greatly improved our understanding of heart development and diseases, and provide a new strategy for heart regenerative therapy. (Circ J 2016; 80: 2081-2088).

  2. Time course of myosin heavy chain transitions in neonatal rats: importance of innervation and thyroid state

    Science.gov (United States)

    Adams, G. R.; McCue, S. A.; Zeng, M.; Baldwin, K. M.

    1999-01-01

    During the postnatal period, rat limb muscles adapt to weight bearing via the replacement of embryonic (Emb) and neonatal (Neo) myosin heavy chains (MHCs) by the adult isoforms. Our aim was to characterize this transition in terms of the six MHC isoforms expressed in skeletal muscle and to determine the importance of innervation and thyroid hormone status on the attainment of the adult MHC phenotype. Neonatal rats were made hypothyroid via propylthiouracil (PTU) injection. In normal and PTU subgroups, leg muscles were unilaterally denervated at 15 days of age. The MHC profiles of plantaris (PLN) and soleus (Sol) muscles were determined at 7, 14, 23, and 30 days postpartum. At day 7, the Sol MHC profile was 55% type I, 30% Emb, and 10% Neo; in the PLN, the pattern was 60% Neo and 25% Emb. By day 30 the Sol and PLN had essentially attained an adult MHC profile in the controls. PTU augmented slow MHC expression in the Sol, whereas in the PLN it markedly repressed IIb MHC by retaining neonatal MHC expression. Denervation blunted the upregulation of IIb in the PLN and of Type I in the Sol and shifted the pattern to greater expression of IIa and IIx MHCs in both muscles. In contrast to previous observations, these findings collectively suggest that both an intact thyroid and innervation state are obligatory for the attainment of the adult MHC phenotype, particularly in fast-twitch muscles.

  3. Measurement of functional cholinergic innervation in rat heart with a novel vesamicol receptor ligand

    International Nuclear Information System (INIS)

    Coffeen, Paul R.; Efange, S.M.N.; Haidet, George C.; McKnite, Scott; Langason, Rosemary B.; Khare, A.B.; Pennington, Jennifer; Lurie, Keith G.

    1996-01-01

    Regional differences in cholinergic activity in the cardiac conduction system have been difficult to study. We tested the utility of (+)-m-[ 125 I]iodobenzyl)trozamicol(+)-[ 125 I]MIBT), a novel radioligand that binds to the vesamicol receptor located on the synaptic vesicle in presynaptic cholinergic neurons, as a functional marker of cholinergic activity in the conduction system. The (+)-[ 125 I]MIBT was injected intravenously into four rats. Three hours later, the rats were killed and their hearts were frozen. Quantitative autoradiography was performed on 20-micron-thick sections that were subsequently stained for acetylcholinesterase to identify specific conduction-system elements. Marked similarities existed between (+)-[ 125 I]MIBT uptake and acetylcholinesterase-positive regions. Optical densitometric analysis of regional (+)-[ 125 I]MIBT uptake revealed significantly greater (+)-[ 125 I]MIBT binding (nCi/mg) in the atrioventricular node (AVN) and His bundle regions compared with other conduction and contractile elements (AVN: 3.43 ± 0.37; His bundle: 2.16 ± 0.30; right bundle branch: 0.95 ± 0.13; right atrium: 0.68 ± 0.05; right ventricle: 0.57 ± 0.03; and left ventricle: 0.57 ± 0.03; p 125 I]MIBT binds avidly to cholinergic nerve tissue innervating specific conduction-system elements. Thus, (+)-[ 125 I]MIBT may be a useful functional marker in studies on cholinergic innervation in the cardiac conduction system

  4. Excessive peptidergic sensory innervation of cutaneous arteriole-venule shunts (AVS) in the palmar glabrous skin of fibromyalgia patients: implications for widespread deep tissue pain and fatigue.

    Science.gov (United States)

    Albrecht, Phillip J; Hou, Quanzhi; Argoff, Charles E; Storey, James R; Wymer, James P; Rice, Frank L

    2013-06-01

    To determine if peripheral neuropathology exists among the innervation of cutaneous arterioles and arteriole-venule shunts (AVS) in fibromyalgia (FM) patients. Cutaneous arterioles and AVS receive a convergence of vasoconstrictive sympathetic innervation, and vasodilatory small-fiber sensory innervation. Given our previous findings of peripheral pathologies in chronic pain conditions, we hypothesized that this vascular location may be a potential site of pathology and/or serotonergic and norepinephrine reuptake inhibitors (SNRI) drug action. Twenty-four female FM patients and nine female healthy control subjects were enrolled for study, with 14 additional female control subjects included from previous studies. AVS were identified in hypothenar skin biopsies from 18/24 FM patient and 14/23 control subjects. Multimolecular immunocytochemistry to assess different types of cutaneous innervation in 3 mm skin biopsies from glabrous hypothenar and trapezius regions. AVS had significantly increased innervation among FM patients. The excessive innervation consisted of a greater proportion of vasodilatory sensory fibers, compared with vasoconstrictive sympathetic fibers. In contrast, sensory and sympathetic innervation to arterioles remained normal. Importantly, the sensory fibers express α2C receptors, indicating that the sympathetic innervation exerts an inhibitory modulation of sensory activity. The excessive sensory innervation to the glabrous skin AVS is a likely source of severe pain and tenderness in the hands of FM patients. Importantly, glabrous AVS regulate blood flow to the skin in humans for thermoregulation and to other tissues such as skeletal muscle during periods of increased metabolic demand. Therefore, blood flow dysregulation as a result of excessive innervation to AVS would likely contribute to the widespread deep pain and fatigue of FM. SNRI compounds may provide partial therapeutic benefit by enhancing the impact of sympathetically mediated inhibitory

  5. Associations between xerostomia, histopathological alterations, and autonomic innervation of labial salivary glands in men in late midlife.

    Science.gov (United States)

    Sørensen, Christiane Elisabeth; Larsen, Jytte Overgaard; Reibel, Jesper; Lauritzen, Martin; Mortensen, Erik Lykke; Osler, Merete; Pedersen, Anne Marie Lynge

    2014-09-01

    One aim of the present study was to investigate whether symptoms of oral dryness (xerostomia) during daytime, assessed in a study group of middle-aged male positive and negative outliers in cognition scores, were associated with age-related degenerative changes in human labial salivary glands and with quantitative measures of the glandular autonomic innervation. Another aim was to study the relation between the autonomic innervation and loss of secretory acinar cells in these glands. Labial salivary gland biopsies were taken from the lower lip from 190 men, born in 1953 and members of the Danish Metropolit birth cohort, who were examined for age-related changes in cognitive function and dental health as part of the Copenhagen University Center for Healthy Aging clinical neuroscience project. The glands were routinely processed and semi-quantitatively analyzed for inflammation, acinar atrophy, fibrosis, and adipocyte infiltration. Sections of labial salivary gland tissue were stained with the panneuronal marker PGP 9.5. In a subsample of 51 participants, the autonomic innervation of the glands was analyzed quantitatively by use of stereology. Labial salivary gland tissue samples from 33% of all participants displayed moderate to severe acinar atrophy and fibrosis (31%). Xerostomia was not significantly associated with structural changes of labial salivary glands, but in the subsample it was inversely related to the total nerve length in the glandular connective tissue. Acinar atrophy and fibrosis were negatively correlated with the parenchymal innervation and positively related to diffuse inflammation. The results from the present study indicate that aspects of the autonomic innervation of labial salivary glands may play a role in the occurrence of xerostomia which in the present study group was not significantly associated with degenerative changes in these glands. The findings further indicate that the integrity of labial salivary gland acini is related to the

  6. Oral epithelial dysplasia classification systems

    DEFF Research Database (Denmark)

    Warnakulasuriya, S; Reibel, J; Bouquot, J

    2008-01-01

    At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the United Kingdom issues related to potentially malignant disorders of the oral cavity were discussed by an expert group. The consensus views of the Working Group are presented in a series of papers....... In this report, we review the oral epithelial dysplasia classification systems. The three classification schemes [oral epithelial dysplasia scoring system, squamous intraepithelial neoplasia and Ljubljana classification] were presented and the Working Group recommended epithelial dysplasia grading for routine...... use. Although most oral pathologists possibly recognize and accept the criteria for grading epithelial dysplasia, firstly based on architectural features and then of cytology, there is great variability in their interpretation of the presence, degree and significance of the individual criteria...

  7. Origins of the sympathetic innervation to the nasal-associated lymphoid tissue (NALT): an anatomical substrate for a neuroimmune connection.

    Science.gov (United States)

    Marafetti, Lucas E; Romeo, Horacio E

    2014-11-15

    The participation of sympathetic nerve fibers in the innervation of the nasal-associated lymphoid tissues (NALT) was investigated in hamsters. Vesicular monoamine transporter 2 (VMAT2), an established sympathetic marker, is expressed in all neurons of superior cervical ganglia (SCG). In addition, VMAT2 -immunoreactive nerve fibers were localized in the NALT as well as in adjacent anatomical structures of the upper respiratory tract. Unilateral surgical ablation of the SCG abolished VMAT2 innervation patterns ipsilaterally while the contra lateral side is unaffected. These results provide the anatomical substrate for a neuroimmune connection in the NALT. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Dynamic Penile Corpora Cavernosa Reconstruction Using Bilateral Innervated Gracilis Muscles: A Preclinical Investigation.

    Science.gov (United States)

    Yin, Zhuming; Liu, Liqiang; Xue, Bingjian; Fan, Jincai; Chen, Wenlin; Liu, Zheng

    2018-03-07

    Prosthesis-assisted penile reconstruction has been performed extensively to restore a cosmetically acceptable phallus. However, a large number of patients will undergo revision surgery for various prosthesis-related complications. To develop a 1-stage prosthesis-free dynamic cavernosa reconstruction method using bilateral innervated gracilis muscles and to investigate the feasibility and reliability of the surgical design. 10 fresh cadavers were dissected to assess the availability of bilateral gracilis muscles for functional cavernosa rebuilding. 11 mongrel female dogs were involved in the penile reconstruction surgery. The neophallus consisted of bilateral gracilis muscles as the neo-cavernosa, a right gracilis skin flap as the neourethra, and a lower abdominal flap with an anterior rectus sheath as the skin envelope and neo-tunica albuginea. The function and structure of the neo-phalli were assessed 7 months postoperatively. The neurovascular pedicle length of the gracilis muscles and the volume of the gracilis venter musculi were measured in the cadaveric investigation. The average dimensions of the canine neo-phalli at rest and during electrostimulated erection were obtained and the muscular fatigue-resistant curve was drawn. Histologic evaluations also were performed. The neurovascular pedicle length and volume of the gracilis muscles were sufficient to yield a nearly normal appearance of the neo-cavernosa in the cadaveric and animal studies. The muscular fatigue-resistant curve demonstrated adequate length, stiffness, and duration of erection of the neo-phalli to accomplish normal coitus. Histologic evaluations showed an intact neourethra and nearly normal muscle structure in the inner layer of the canine neo-cavernosa, except for significantly increased amount of collagen fibers and type I/III collagen ratio in the outer layer of the neo-cavernosa. The percentage of type II (fatigue-prone) muscle fibers did not change significantly. Our preclinical

  9. The vestibular nerve of the chinchilla. III. Peripheral innervation patterns in the utricular macula

    Science.gov (United States)

    Fernandez, C.; Goldberg, J. M.; Baird, R. A.

    1990-01-01

    1. Nerve fibers supplying the utricular macula of the chinchilla were labeled by extracellular injection of horseradish peroxidase into the vestibular nerve. The peripheral terminations of individual fibers were reconstructed and related to the regions of the end organ they innervated and to the sizes of their parent axons. 2. The macula is divided into medial and lateral parts by the striola, a narrow zone that runs for almost the entire length of the sensory epithelium. The striola can be distinguished from the extrastriolar regions to either side of it by the wider spacing of its hair cells. Calyx endings in the striola have especially thick walls, and, unlike similar endings in the extrastriola, many of them innervate more than one hair cell. The striola occupies 10% of the sensory epithelium; the lateral extrastriola, 50%; and the medial extrastriola, 40%. 3. The utricular nerve penetrates the bony labyrinth anterior to the end organ. Axons reaching the anterior part of the sensory epithelium run directly through the connective tissue stroma. Those supplying more posterior regions first enter a fiber layer located at the bottom of the stroma. Approximately one-third of the axons bifurcate below the epithelium, usually within 5-20 microns of the basement membrane. Bifurcations are more common in fibers destined for the extrastriola than for the striola. 4. Both calyx and bouton endings were labeled. Calyces can be simple or complex. Simple calyces innervate individual hair cells, whereas complex calyces supply 2-4 adjacent hair cells. Complex endings are more heavily concentrated in the striola than in the extrastriola. Simple calyces and boutons are found in all parts of the epithelium. Calyces emerge from the parent axon or one of its thick branches. Boutons, whether en passant or terminal, are located on thin collaterals. 5. Fibers can be classified into calyx, bouton, or dimorphic categories. The first type only has calyx endings; the second, only bouton

  10. Function and innervation of the locus ceruleus in a macaque model of Functional Hypothalamic Amenorrhea.

    Science.gov (United States)

    Bethea, Cynthia L; Kim, Aaron; Cameron, Judy L

    2013-02-01

    A body of knowledge implicates an increase in output from the locus ceruleus (LC) during stress. We questioned the innervation and function of the LC in our macaque model of Functional Hypothalamic Amenorrhea, also known as Stress-Induced Amenorrhea. Cohorts of macaques were initially characterized as highly stress resilient (HSR) or stress-sensitive (SS) based upon the presence or absence of ovulation during a protocol involving 2 menstrual cycles with psychosocial and metabolic stress. Afterwards, the animals were rested until normal menstrual cycles resumed and then euthanized on day 5 of a new menstrual cycle [a] in the absence of further stress; or [b] after 5 days of resumed psychosocial and metabolic stress. In this study, parameters of the LC were examined in HSR and SS animals in the presence and absence of stress (2×2 block design) using ICC and image analysis. Tyrosine hydroxylase (TH) is the rate-limiting enzyme for the synthesis of catecholamines; and the TH level was used to assess by inference, NE output. The pixel area of TH-positive dendrites extending outside the medial border of the LC was significantly increased by stress to a similar degree in both HSR and SS animals (p<0.0001). There is a significant CRF innervation of the LC. The positive pixel area of CRF boutons, lateral to the LC, was higher in SS than HSR animals in the absence of stress. Five days of moderate stress significantly increased the CRF-positive bouton pixel area in the HSR group (p<0.02), but not in the SS group. There is also a significant serotonin innervation of the LC. A marked increase in medial serotonin dendrite swelling and beading was observed in the SS+stress group, which may be a consequence of excitotoxicity. The dendrite beading interfered with analysis of axonal boutons. However, at one anatomical level, the serotonin-positive bouton area was obtained between the LC and the superior cerebellar peduncle. Serotonin-positive bouton pixel area was significantly

  11. Central Somatosensory Networks Respond to a De Novo Innervated Penis : A Proof of Concept in Three Spina Bifida Patients

    NARCIS (Netherlands)

    Kortekaas, Rudie; Nanetti, Luca; Overgoor, Max L. E.; de Jong, Bauke M.; Georgiadis, Janniko R.

    Introduction. Spina bifida (SB) causes low spinal lesions, and patients often have absent genital sensation and a highly impaired sex life. TOMAX (TO MAX-imize sensation, sexuality and quality of life) is a surgical procedure whereby the penis is newly innervated using a sensory nerve originally

  12. MRI-based 3D pelvic autonomous innervation: a first step towards image-guided pelvic surgery

    Energy Technology Data Exchange (ETDEWEB)

    Bertrand, M.M. [University Montpellier I, Laboratory of Experimental Anatomy Faculty of Medicine Montpellier-Nimes, Montpellier (France); Macri, F.; Beregi, J.P. [Nimes University Hospital, University Montpellier 1, Radiology Department, Nimes (France); Mazars, R.; Prudhomme, M. [University Montpellier I, Laboratory of Experimental Anatomy Faculty of Medicine Montpellier-Nimes, Montpellier (France); Nimes University Hospital, University Montpellier 1, Digestive Surgery Department, Nimes (France); Droupy, S. [Nimes University Hospital, University Montpellier 1, Urology-Andrology Department, Nimes (France)

    2014-08-15

    To analyse pelvic autonomous innervation with magnetic resonance imaging (MRI) in comparison with anatomical macroscopic dissection on cadavers. Pelvic MRI was performed in eight adult human cadavers (five men and three women) using a total of four sequences each: T1, T1 fat saturation, T2, diffusion weighed. Images were analysed with segmentation software in order to extract nervous tissue. Key height points of the pelvis autonomous innervation were located in every specimen. Standardised pelvis dissections were then performed. Distances between the same key points and the three anatomical references forming a coordinate system were measured on MRIs and dissections. Concordance (Lin's concordance correlation coefficient) between MRI and dissection was calculated. MRI acquisition allowed an adequate visualization of the autonomous innervation. Comparison between 3D MRI images and dissection showed concordant pictures. The statistical analysis showed a mean difference of less than 1 cm between MRI and dissection measures and a correct concordance correlation coefficient on at least two coordinates for each point. Our acquisition and post-processing method demonstrated that MRI is suitable for detection of autonomous pelvic innervations and can offer a preoperative nerve cartography. (orig.)

  13. Central projections of the sensory innervation of the rat middle meningeal artery

    DEFF Research Database (Denmark)

    Liu, Y.; Broman, J.; Edvinsson, L.

    2008-01-01

    Headaches, especially migraine, involve not only pain but also aspects such as vasodilation of cranial vessels and sensitization of nerve endings, processes dependent on and connected to the central nervous system. To understand pathogenic mechanisms of headache, it is important to elucidate...... the central projections of sensory nerves that innervate cranial vessels, of which the middle meningeal artery (MMA) is the largest artery supplying the dura mater. In this study, cholera toxin subunit b (CTb) or wheat germ agglutinin-horseradish peroxidase conjugate (WGA-HRP) was applied on the adventitia....... Labeled nerve terminations were found ipsilaterally in the lateral part of the spinal dorsal horn of segments C1-C3 and in the caudal and interpolar parts of the spinal trigeminal nucleus. WGA-HRP labeled terminations were mainly located in laminae I and II, whereas CTb labeled terminations located...

  14. Reconstructing the population activity of olfactory output neurons that innervate identifiable processing units

    Directory of Open Access Journals (Sweden)

    Shigehiro Namiki

    2008-06-01

    Full Text Available We investigated the functional organization of the moth antennal lobe (AL, the primary olfactory network, using in vivo electrophysiological recordings and anatomical identification. The moth AL contains about 60 processing units called glomeruli that are identifiable from one animal to another. We were able to monitor the output information of the AL by recording the activity of a population of output neurons, each of which innervated a single glomerulus. Using compiled intracellular recordings and staining data from different animals, we mapped the odor-evoked dynamics on a digital atlas of the AL and geometrically reconstructed the population activity. We examined the quantitative relationship between the similarity of olfactory responses and the anatomical distance between glomeruli. Globally, the olfactory response profile was independent of the anatomical distance, although some local features were present.

  15. Innervation zones of fasciculating motor units: observations by a linear electrode array.

    Science.gov (United States)

    Jahanmiri-Nezhad, Faezeh; Barkhaus, Paul E; Rymer, William Z; Zhou, Ping

    2015-01-01

    This study examines the innervation zone (IZ) in the biceps brachii muscle in healthy subjects and those with amyotrophic lateral sclerosis (ALS) using a 20-channel linear electromyogram (EMG) electrode array. Raster plots of individual waveform potentials were studied to estimate the motor unit IZ. While this work mainly focused on fasciculation potentials (FPs), a limited number of motor unit potentials (MUPs) from voluntary activity of 12 healthy and seven ALS subjects were also examined. Abnormal propagation of MUPs and scattered IZs were observed in fasciculating units, compared with voluntarily activated MUPs in healthy and ALS subjects. These findings can be related to muscle fiber reinnervation following motor neuron degeneration in ALS and the different origin sites of FPs compared with voluntary MUPs.

  16. Changes of the vasculature and innervation in the anterior segment of the RCS rat eye.

    Science.gov (United States)

    May, Christian Albrecht

    2011-12-01

    Investigating the anterior eye segment vasculature and innervation of dystrophic RCS rats, two major unique findings were observed: in the iris, young adult animals with retinal dystrophy showed an increase in substance P nerve fibres and a dilation of arterioles and capillaries. This finding continued during ageing. In the pars plana region, the surface covered by venules decreased continuously with age. In older animals, this decrease was parallelled by a local decrease of sympathetic TH-positive nerve fibres supplying these venules. For both conditions, no comparable data exists so far in the literature. They might point to a unique situation in the anterior eye segment of the dystrophic RCS rat. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Dynamic interaction between the heart and its sympathetic innervation following T5 spinal cord transection.

    Science.gov (United States)

    Lujan, Heidi L; Janbaih, Hussein; DiCarlo, Stephen E

    2012-10-15

    Midthoracic spinal cord injury (SCI) is associated with enhanced sympathetic support of heart rate as well as myocardial damage related to calcium overload. The myocardial damage may elicit an enhanced sympathetic support of contractility to maintain ventricular function. In contrast, the level of inotropic drive may be reduced to match the lower afterload that results from the injury-induced reduction in arterial pressure. Accordingly, the inotropic response to midthoracic SCI may be increased or decreased but has not been investigated and therefore remains unknown. Furthermore, the altered ventricular function may be associated with anatomical changes in cardiac sympathetic innervation. To determine the inotropic drive following midthoracic SCI, a telemetry device was used for repeated measurements of left ventricular (LV) function, with and without beta-adrenergic receptor blockade, in rats before and after midthoracic SCI or sham SCI. In addition, NGF content (ELISA) and dendritic arborization (cholera toxin B immunohistochemistry and Sholl analysis) of cardiac-projecting sympathetic postganglionic neurons in the stellate ganglia were determined. Midthoracic SCI was associated with an enhanced sympathetic support of heart rate, dP/dt(+), and dP/dt(-). Importantly, cardiac function was lower following blockade of the sympathetic nervous system in rats with midthoracic SCI compared with sham-operated rats. Finally, these functional neuroplastic changes were associated with an increased NGF content and structural neuroplasticity within the stellate ganglia. Results document impaired LV function with codirectional changes in chronotropic and inotropic responses following midthoracic SCI. These functional changes were associated with a dynamic interaction between the heart and its sympathetic innervation.

  18. Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine

    Science.gov (United States)

    Parnaudeau, Sébastien; Dongelmans, Marie-louise; Turiault, Marc; Ambroggi, Frédéric; Delbes, Anne-Sophie; Cansell, Céline; Luquet, Serge; Piazza, Pier-Vincenzo; Tronche, François; Barik, Jacques

    2014-01-01

    The meso-cortico-limbic system, via dopamine release, encodes the rewarding and reinforcing properties of natural rewards. It is also activated in response to abused substances and is believed to support drug-related behaviors. Dysfunctions of this system lead to several psychiatric conditions including feeding disorders and drug addiction. These disorders are also largely influenced by environmental factors and in particular stress exposure. Stressors activate the corticotrope axis ultimately leading to glucocorticoid hormone (GCs) release. GCs bind the glucocorticoid receptor (GR) a transcription factor ubiquitously expressed including within the meso-cortico-limbic tract. While GR within dopamine-innervated areas drives cocaine's behavioral responses, its implication in responses to other psychostimulants such as amphetamine has never been clearly established. Moreover, while extensive work has been made to uncover the role of this receptor in addicted behaviors, its contribution to the rewarding and reinforcing properties of food has yet to be investigated. Using mouse models carrying GR gene inactivation in either dopamine neurons or in dopamine-innervated areas, we found that GR in dopamine responsive neurons is essential to properly build amphetamine-induced conditioned place preference and locomotor sensitization. c-Fos quantification in the nucleus accumbens further confirmed defective neuronal activation following amphetamine injection. These diminished neuronal and behavioral responses to amphetamine may involve alterations in glutamate transmission as suggested by the decreased MK801-elicited hyperlocomotion and by the hyporeactivity to glutamate of a subpopulation of medium spiny neurons. In contrast, GR inactivation did not affect rewarding and reinforcing properties of food suggesting that responding for natural reward under basal conditions is preserved in these mice. PMID:24574986

  19. Thermoreceptive innervation of human glabrous and hairy skin: a contact heat evoked potential analysis.

    Science.gov (United States)

    Granovsky, Yelena; Matre, Dagfinn; Sokolik, Alexander; Lorenz, Jürgen; Casey, Kenneth L

    2005-06-01

    The human palm has a lower heat detection threshold and a higher heat pain threshold than hairy skin. Neurophysiological studies of monkeys suggest that glabrous skin has fewer low threshold heat nociceptors (AMH type 2) than hairy skin. Accordingly, we used a temperature-controlled contact heat evoked potential (CHEP) stimulator to excite selectively heat receptors with C fibers or Adelta-innervated AMH type 2 receptors in humans. On the dorsal hand, 51 degrees C stimulation produced painful pinprick sensations and 41 degrees C stimuli evoked warmth. On the glabrous thenar, 41 degrees C stimulation produced mild warmth and 51 degrees C evoked strong but painless heat sensations. We used CHEP responses to estimate the conduction velocities (CV) of peripheral fibers mediating these sensations. On hairy skin, 41 degrees C stimuli evoked an ultra-late potential (mean, SD; N wave latency: 455 (118) ms) mediated by C fibers (CV by regression analysis: 1.28 m/s, N=15) whereas 51 degrees C stimuli evoked a late potential (N latency: 267 (33) ms) mediated by Adelta afferents (CV by within-subject analysis: 12.9 m/s, N=6). In contrast, thenar responses to 41 and 51 degrees C were mediated by C fibers (average N wave latencies 485 (100) and 433 (73) ms, respectively; CVs 0.95-1.35 m/s by regression analysis, N=15; average CV=1.7 (0.41) m/s calculated from distal glabrous and proximal hairy skin stimulation, N=6). The exploratory range of the human and monkey palm is enhanced by the abundance of low threshold, C-innervated heat receptors and the paucity of low threshold AMH type 2 heat nociceptors.

  20. Perianal implantation of bioengineered human internal anal sphincter constructs intrinsically innervated with human neural progenitor cells.

    Science.gov (United States)

    Raghavan, Shreya; Miyasaka, Eiichi A; Gilmont, Robert R; Somara, Sita; Teitelbaum, Daniel H; Bitar, Khalil N

    2014-04-01

    The internal anal sphincter (IAS) is a major contributing factor to pressure within the anal canal and is required for maintenance of rectoanal continence. IAS damage or weakening results in fecal incontinence. We have demonstrated that bioengineered, intrinsically innervated, human IAS tissue replacements possess key aspects of IAS physiology, such as the generation of spontaneous basal tone and contraction/relaxation in response to neurotransmitters. The objective of this study is to demonstrate the feasibility of implantation of bioengineered IAS constructs in the perianal region of athymic rats. Human IAS tissue constructs were bioengineered from isolated human IAS circular smooth muscle cells and human enteric neuronal progenitor cells. After maturation of the bioengineered constructs in culture, they were implanted operatively into the perianal region of athymic rats. Platelet-derived growth factor was delivered to the implanted constructs through a microosmotic pump. Implanted constructs were retrieved from the animals 4 weeks postimplantation. Animals tolerated the implantation well, and there were no early postoperative complications. Normal stooling was observed during the implantation period. At harvest, implanted constructs were adherent to the perirectal rat tissue and appeared healthy and pink. Immunohistochemical analysis revealed neovascularization. Implanted smooth muscle cells maintained contractile phenotype. Bioengineered constructs responded in vitro in a tissue chamber to neuronally evoked relaxation in response to electrical field stimulation and vasoactive intestinal peptide, indicating the preservation of neuronal networks. Our results indicate that bioengineered innervated IAS constructs can be used to augment IAS function in an animal model. This is a regenerative medicine based therapy for fecal incontinence that would directly address the dysfunction of the IAS muscle. Copyright © 2014 Mosby, Inc. All rights reserved.

  1. Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine

    Directory of Open Access Journals (Sweden)

    Sebastien eParnaudeau

    2014-02-01

    Full Text Available The meso-cortico-limbic system, via dopamine release, encodes the rewarding and reinforcing properties of natural rewards. It is also activated in response to abused substances and is believed to support drug-related behaviors. Dysfunctions of this system lead to several psychiatric conditions including feeding disorders and drug addiction. These disorders are also largely influenced by environmental factors and in particular stress exposure. Stressors activate the corticotrope axis ultimately leading to glucocorticoid hormone (GCs release. GCs bind the glucocorticoid receptor (GR a transcription factor ubiquitously expressed including within the meso-cortico-limbic tract. While the GR within dopamine-innervated areas drives cocaine’s behavioral responses, its implication in responses to other psychostimulants such as amphetamine has never been clearly established. Moreover, while extensive work has been made to uncover the role of this receptor in addicted behaviors, its contribution to the rewarding and reinforcing properties of food has yet to be investigated. Using mouse models carrying GR gene inactivation in either dopamine neurons or in dopamine-innervated areas, we found that GR in dopamine responsive neurones is essential to properly build amphetamine-induced conditioned place preference and locomotor sensitization. c-Fos quantification in the nucleus accumbens further confirmed defective neuronal activation following amphetamine injection. These diminished neuronal and behavioral responses to amphetamine may involve alterations in glutamate transmission as suggested by the decreased MK801-elicited hyperlocomotion and by the hyporeactivity to glutamate of a subpopulation of medium spiny neurons. In contrast, GR inactivation did not affect rewarding and reinforcing properties of food suggesting that responding for natural reward under basal conditions is preserved in these mice.

  2. Efferent innervation of turtle semicircular canal cristae: comparisons with bird and mouse

    Science.gov (United States)

    Jordan, Paivi M.; Fettis, Margaret; Holt, Joseph C.

    2014-01-01

    In the vestibular periphery of nearly every vertebrate, cholinergic vestibular efferent neurons give rise to numerous presynaptic varicosities that target hair cells and afferent processes in the sensory neuroepithelium. Although pharmacological studies have described the postsynaptic actions of vestibular efferent stimulation in several species, characterization of efferent innervation patterns and the relative distribution of efferent varicosities among hair cells and afferents are also integral to understanding how efferent synapses operate. Vestibular efferent markers, however, have not been well characterized in the turtle, one of the animal models utilized by our laboratory. Here, we sought to identify reliable efferent neuronal markers in the vestibular periphery of turtle, to utilize these markers to understand how efferent synapses are organized, and to compare efferent neuronal labeling patterns in turtle with two other amniotes using some of the same markers. Efferent fibers and varicosities were visualized in the semicircular canal of Red-Eared Turtles (Trachemys scripta elegans), Zebra Finches (Taeniopygia guttata), and mice (Mus musculus) utilizing fluorescent immunohistochemistry with antibodies against choline acetyltransferase (ChAT). Vestibular hair cells and afferents were counterstained using antibodies to myosin VIIa and calretinin. In all species, ChAT labeled a population of small diameter fibers giving rise to numerous spherical varicosities abutting type II hair cells and afferent processes. That these ChAT-positive varicosities represent presynaptic release sites were demonstrated by colabeling with antibodies against the synaptic vesicle proteins synapsin I, SV2, or syntaxin and the neuropeptide calcitonin gene-related peptide (CGRP). Comparisons of efferent innervation patterns among the three species are discussed. PMID:25560461

  3. Innervation status in chronic vocal fold paralysis and implications for laryngeal reinnervation.

    Science.gov (United States)

    Lin, R Jun; Smith, Libby J; Munin, Michael C; Sridharan, Shaum; Rosen, Clark A

    2018-01-22

    Treatment options for symptomatic unilateral vocal fold paralysis (VFP) include vocal fold augmentation, laryngeal framework surgery, and laryngeal reinnervation. Laryngeal reinnervation (LR) has been suggested to provide "tone" to the paralyzed VF. This implies a loss of tone as a result of denervation without reinnervation. We performed laryngeal electromyography (LEMG) in patients with chronic VFP to understand the innervation status associated with a chronically paralyzed vocal fold. Retrospective review of LEMG data in adult patients with chronic VFP from January 2009 to December 2014. LEMG was performed at least 6 months after-onset of VFP. Qualitative LEMG, quantitative LEMG, and adductory synkinesis testing were performed, and the parameters were collected. Twenty-seven vocal folds were studied (23 unilateral VFP and 2 bilateral VFP). Average age was 59 ± 17 years. The median duration from recurrent laryngeal nerve injury to LEMG was 8.5 months (range 6-90 months). The majority of patients, 24 of 27 (89%), had motor unit potentials during phonation tasks on LEMG, and only 3 of 27 (11%) patients were electrically silent. Quantitative LEMG showed 287.8 mean turns per second (normal ≥ 400). Motor unit configuration was normal in 12 of 27 (44%), polyphasic in 12 of 27 (44%), and absent in the electrically silent patients. Adductory synkinesis was found in 6 of 20 (30%) patients. Chronic vocal fold paralysis is infrequently associated with absent motor-unit recruitment, indicating some degree of preserved innervation and/or reinnervation in these patients. LEMG should be part of the routine workup for chronic VFP prior to consideration of LR. 4. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

  4. Ontogeny and innervation of taste buds in mouse palatal gustatory epithelium.

    Science.gov (United States)

    Rashwan, Ahmed; Konishi, Hiroyuki; El-Sharaby, Ashraf; Kiyama, Hiroshi

    2016-01-01

    We investigated the relationship between mouse taste bud development and innervation of the soft palate. We employed scanning electron microscopy and immunohistochemistry using antibodies against protein gene product 9.5 and peripherin to detect sensory nerves, and cytokeratin 8 and α-gustducin to stain palatal taste buds. At E14, nerve fibers were observed along the medial border of the palatal shelves that tracked toward the epithelium. At E15.5, primordial stages of taste buds in the basal lamina of the soft palate first appeared. At E16, the taste buds became large spherical masses of columnar cells scattered in the soft palate basal lamina. At E17, the morphology and also the location of taste buds changed. At E18-19, some taste buds acquired a more elongated shape with a short neck, extending a variable distance from the soft palate basal lamina toward the surface epithelium. At E18, mature taste buds with taste pores and perigemmal nerve fibers were observed on the surface epithelium of the soft palate. The expression of α-gustducin was demonstrated at postnatal day 1 and the number of pored taste buds increased with age and they became pear-shaped at 8 weeks. The percent of pored fungiform-like papillae at birth was 58.3% of the whole palate; this increased to 83.8% at postnatal day 8 and reached a maximum of 95.7% at 12 weeks. The innervation of the soft palate was classified into three types of plexuses in relation to taste buds: basal nerve plexus, intragemmal and perigemmal nerve fibers. This study reveals that the nerve fibers preceded the development of taste buds in the palate of mice, and therefore the nerve fibers have roles in the initial induction of taste buds in the soft palate. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Coordinated Respiratory Motor Activity in Nerves Innervating the Upper Airway Muscles in Rats.

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    Satoshi Tachikawa

    Full Text Available Maintaining the patency of the upper airway during breathing is of vital importance. The activity of various muscles is related to the patency of the upper airway. In the present study, we examined the respiratory motor activity in the efferent nerves innervating the upper airway muscles to determine the movements of the upper airway during respiration under normocapnic conditions (pH = 7.4 and in hypercapnic acidosis (pH = 7.2. Experiments were performed on arterially perfused decerebrate rats aged between postnatal days 21-35. We recorded the efferent nerve activity in a branch of the cervical spinal nerve innervating the infrahyoid muscles (CN, the hypoglossal nerve (HGN, the external branch of the superior laryngeal nerve (SLN, and the recurrent laryngeal nerve (RLN with the phrenic nerve (PN. Inspiratory nerve discharges were observed in all these nerves under normocapnic conditions. The onset of inspiratory discharges in the CN and HGN was slightly prior to those in the SLN and RLN. When the CO2 concentration in the perfusate was increased from 5% to 8% to prepare for hypercapnic acidosis, the peak amplitudes of the inspiratory discharges in all the recorded nerves were increased. Moreover, hypercapnic acidosis induced pre-inspiratory discharges in the CN, HGN, SLN, and RLN. The onset of pre-inspiratory discharges in the CN, HGN, and SLN was prior to that of discharges in the RLN. These results suggest that the securing of the airway that occurs a certain time before dilation of the glottis may facilitate ventilation and improve hypercapnic acidosis.

  6. Proliferation of epithelial rests of Malassez following auto-transplantation of third molars: a case report

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    Schepers Serge

    2010-10-01

    Full Text Available Abstract Introduction Auto-transplantation of third molars is frequently undertaken in order to restore a perfect occlusion and to improve mastication following a substantial loss of molars. However, little is known about the precise role of the periodontal membrane during this procedure. Therefore, we investigated if the epithelial rests of Malassez persist in the periodontal ligament of auto-transplanted teeth and, if so, whether these may show signs of a neuro-epithelial relationship. Case presentation We report a case of a 21-year-old Caucasian woman who underwent an auto-transplantation of two third molars. After two years, renewed progressive caries of the auto-transplanted teeth led to the removal of the auto-transplanted elements. The periodontal ligament was removed and studied with a light and transmission electron microscope. Conclusion In this report we examined the ultrastructure of the periodontal ligament after auto-transplantation in order to see if the periodontal ligament recovers completely from this intervention. We observed fully developed blood vessels and a re-innervation of the epithelial rests of Malassez which were proliferating following auto-transplantation. This proliferation might be critical in the remodelling of the alveolar socket in order to provide a perfect fit for the transplanted tooth. In order to minimalise the damage to the epithelial rests of Malassez, the extraction of the tooth should be as atraumatic as possible in order to provide an optimal conservation of the periodontal ligament which will be beneficial to the healing-process.

  7. Surgical management of epithelial parotid tumours

    International Nuclear Information System (INIS)

    Obaid, M.A.; Yusuf, A.

    2004-01-01

    Objective: To describe the clinicopathological presentation and treatment options in epithelial parotid tumours with emphasis on surgery. Subjects and Methods: Epithelial parotid tumours diagnosed and operated by an ENT surgeon and a general surgeon in 10 years during their posting in different teaching hospitals were included in the study. Clinical presentation, preoperative investigations, operative procedure, histopathology report, postoperative complications and further management were recorded. The data was collected and reviewed from the records of all the patients maintained by the authors. Results: Fifty-two patients presented with parotid tumour. Average age was 38 years. Commonest presentation was painless lump over the parotid region (85%), pain (15%), facial palsy, and enlarged neck nodes. Majority of tumours were benign, only two were recurrent. Parotid pleomorphic Adenoma (PPA) was the commonest benign tumour, others being Warthin's tumour and monomorphic adenoma. Adenoid cystic carcinoma was the commonest malignant tumour 29% followed by mucoepidermoid carcinoma. Others were carcinoma in PPA squamous cell carcinoma, malignant mixed tumour, malignant Iymphoepithelioma and undifferentiated carcinoma. Superficial parotidectomy (SP) was the commonest operation performed in 69%. Other procedures were total conservative parotidectomy in 11%, total radical surgery in 9% and enucleation in only one patient earliest in the series. Neck node dissection was done in 2 patients. Except for one child, rest of the 13 patients received postoperative radiotherapy and one patient of Iymphoepithelioma received chemotherapy in addition. Commonest postoperative complication was temporary facial weakness in 35% (18/52). Permanent facial palsy occurred in 08 patients. Of these 07 had a malignant process and only one patient had excision biopsy. Conclusion: Benign and malignant epithelial parotid tumours can be diagnosed by there clinical presentation . supplemented with

  8. Multiple Identified Neurons and Peripheral Nerves Innervating the Prothoracic Defense Glands in Stick Insects Reveal Evolutionary Conserved and Novel Elements of a Chemical Defense System

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    Johannes Strauß

    2017-11-01

    Full Text Available The defense glands in the dorsal prothorax are an important autapomorphic trait of stick insects (Phasmatodea. Here, we study the functional anatomy and neuronal innervation of the defense glands in Anisomorpha paromalus (Westwood, 1859 (Pseudophasmatinae, a species which sprays its defense secretions when disturbed or attacked. We use a neuroanatomical approach to identify the nerves innervating the gland muscles and the motoneurons with axons in the different nerves. The defense gland is innervated by nerves originating from two segments, the subesophageal ganglion (SOG, and the prothoracic ganglion. Axonal tracing confirms the gland innervation via the anterior subesophageal nerve, and two intersegmental nerves, the posterior subesophageal nerve, and the anterior prothoracic nerve. Axonal tracing of individual nerves reveals eight identified neuron types in the subesophageal or prothoracic ganglion. The strongest innervating nerve of the gland is the anterior subesophageal nerve, which also supplies dorsal longitudinal thorax muscles (neck muscles by separate nerve branches. Tracing of individual nerve branches reveals different sets of motoneurons innervating the defense gland (one ipsilateral and one contralateral subesophageal neuron or the neck muscle (ventral median neurons. The ipsilateral and contralateral subesophageal neurons have no homologs in related taxa like locusts and crickets, and thus evolved within stick insects with the differentiation of the defense glands. The overall innervation pattern suggests that the longitudinal gland muscles derived from dorsal longitudinal neck muscles. In sum, the innervating nerves for dorsal longitudinal muscles are conserved in stick insects, while the neuronal control system was specialized with conserved motoneurons for the persisting neck muscles, and evolutionarily novel subesophageal and prothoracic motoneurons innervating the defense gland.

  9. Postnatal remodeling of the neural components of the epithelial-mesenchymal trophic unit in the proximal airways of infant rhesus monkeys exposed to ozone and allergen.

    Science.gov (United States)

    Larson, Shawnessy D; Schelegle, Edward S; Walby, William F; Gershwin, Laural J; Fanuccihi, Michelle V; Evans, Michael J; Joad, Jesse P; Tarkington, Brian K; Hyde, Dallas M; Plopper, Charles G

    2004-02-01

    Nerves and neuroendocrine cells located within the airway epithelium are ideally situated to sample a changing airway environment, to transmit that information to the central nervous system, and to promote trophic interactions between epithelial and mesenchymal cellular and acellular components. We tested the hypothesis that the environmental stresses of ozone (O(3)) and house dust mite allergen (HDMA) in atopic infant rhesus monkeys alter the distribution of airway nerves. Midlevel bronchi and bronchioles from 6-month-old infant monkeys that inhaled filtered air (FA), house dust mite allergen HDMA, O(3), or HDMA + O(3) for 11 episodes (5 days each, 0.5 ppm O(3), 8 h/day followed by 9 days recovery) were examined using immunohistochemistry for the presence of Protein gene product 9.5 (PGP 9.5), a nonspecific neural indicator, and calcitonin gene-related peptide (CGRP). Along the axial path between the sixth and the seventh intrapulmonary airway generations, there were small significant (P < 0.05) decrements in the density of epithelial nerves in monkeys exposed to HDMA or O(3), while in monkeys exposed to HDMA + O(3) there was a greater significant (P < 0.05) reduction in epithelial innervation. In animals exposed to O(3) or HDMA + O(3) there was a significant increase in the number of PGP 9.5 positive/CGRP negative cells that were anchored to the basal lamina and emitted projections in primarily the lateral plain and often intertwined with projections and cell bodies of other similar cells. We conclude that repeated cycles of acute injury and repair associated with the episodic pattern of ozone and allergen exposure alter the normal development of neural innervation of the epithelial compartment and the appearance of a new population of undefined PGP 9.5 positive cells within the epithelium.

  10. Axo-somatic synapses in the normal and X-irradiated dendate gyrus; factors affecting the density of afferent innervation

    International Nuclear Information System (INIS)

    Lee, K.S.; Gerbrandt, L.; Lynch, G.

    1982-01-01

    The density of synaptic input to the somata of dentate gyrus granule cells was examined utilizing quantitative electron microscopic techniques. In control (non-irradiated) material, greater numbers of axo-somatic synapses were observed in the superficial, earlier-generated cells as compared to the deep, later-generated cells. We further studied the X-irradiated dentate gyrus, in which the majority of granule cells were destroyed during postnatal genesis. The surviving cells displayed a density of innervation on their somata which exceeded that observed in either layer of the control material. These data are discussed in terms of the possible contribution of afferent-target cell interactions to the regulation of the density of synaptic innervation. (Auth.)

  11. Axo-somatic synapses in the normal and X-irradiated dendate gyrus; factors affecting the density of afferent innervation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, K S [Max-Planck-Institut fuer Psychiatrie, Muenchen (Germany, F.R.); Gerbrandt, L [Neuroscience Research Program, Boston, MA (USA); Lynch, G [California Univ., Irvine (USA)

    1982-10-07

    The density of synaptic input to the somata of dentate gyrus granule cells was examined utilizing quantitative electron microscopic techniques. In control (non-irradiated) material, greater numbers of axo-somatic synapses were observed in the superficial, earlier-generated cells as compared to the deep, later-generated cells. We further studied the X-irradiated dentate gyrus, in which the majority of granule cells were destroyed during postnatal genesis. The surviving cells displayed a density of innervation on their somata which exceeded that observed in either layer of the control material. These data are discussed in terms of the possible contribution of afferent-target cell interactions to the regulation of the density of synaptic innervation.

  12. Structural organization and pattern of innervations of human Meissner’s corpuscle: a light microscopic study

    OpenAIRE

    Gh. Mohd. Bhat; Naseer Ahmad Shah; Mohd. Saleem Itoo; Bashir Ahmad Shah; Shaheen Shahdad; Javeed Ahmad Khan

    2013-01-01

    Background: Human glabrous skin has very rich nerve supply in the form of specialized nerve endings like Meissner’s corpuscles, Pacinian corpuscles, Krause end bulbs etc for carrying sensory information to brain. Aim of study: To study the structure, pattern of innervations and nerve terminations of human Meissner’s corpuscle. Methods: Skin samples from sixty human beings (age range 2 to 72 years) were taken, sections prepared and stained with a cytological (Haematoxylin – Eosi...

  13. Effect of altered innervation and thyroid hormones on myosin heavy chain expression and fiber type transitions: a mini-review

    Czech Academy of Sciences Publication Activity Database

    Soukup, Tomáš; Smerdu, V.

    2015-01-01

    Roč. 143, č. 2 (2015), s. 123-130 ISSN 0948-6143 R&D Projects: GA MŠk(CZ) LH12058; GA MŠk(CZ) 7AMB14SK123 Grant - others:EC(XE) LSH-CT-2004-511978 Institutional support: RVO:67985823 Keywords : muscle fiber types * muscle regeneration * muscle transplantation * MyHC isoforms * thyroid hormone status * innervation Subject RIV: EA - Cell Biology Impact factor: 2.780, year: 2015

  14. Effects of catheter-based renal denervation on cardiac sympathetic activity and innervation in patients with resistant hypertension.

    Science.gov (United States)

    Donazzan, Luca; Mahfoud, Felix; Ewen, Sebastian; Ukena, Christian; Cremers, Bodo; Kirsch, Carl-Martin; Hellwig, Dirk; Eweiwi, Tareq; Ezziddin, Samer; Esler, Murray; Böhm, Michael

    2016-04-01

    To investigate, whether renal denervation (RDN) has a direct effect on cardiac sympathetic activity and innervation density. RDN demonstrated its efficacy not only in reducing blood pressure (BP) in certain patients, but also in decreasing cardiac hypertrophy and arrhythmias. These pleiotropic effects occur partly independent from the observed BP reduction. Eleven patients with resistant hypertension (mean office systolic BP 180 ± 18 mmHg, mean antihypertensive medications 6.0 ± 1.5) underwent I-123-mIBG scintigraphy to exclude pheochromocytoma. We measured cardiac sympathetic innervation and activity before and 9 months after RDN. Cardiac sympathetic innervation was assessed by heart to mediastinum ratio (H/M) and sympathetic activity by wash out ratio (WOR). Effects on office BP, 24 h ambulatory BP monitoring, were documented. Office systolic BP and mean ambulatory systolic BP were significantly reduced from 180 to 141 mmHg (p = 0.006) and from 149 to 129 mmHg (p = 0.014), respectively. Cardiac innervation remained unchanged before and after RDN (H/M 2.5 ± 0.5 versus 2.6 ± 0.4, p = 0.285). Cardiac sympathetic activity was significantly reduced by 67 % (WOR decreased from 24.1 ± 12.7 to 7.9 ± 25.3 %, p = 0.047). Both, responders and non-responders experienced a reduction of cardiac sympathetic activity. RDN significantly reduced cardiac sympathetic activity thereby demonstrating a direct effect on the heart. These changes occurred independently from BP effects and provide a pathophysiological basis for studies, investigating the potential effect of RDN on arrhythmias and heart failure.

  15. Acute stimulation of brain mu opioid receptors inhibits glucose-stimulated insulin secretion via sympathetic innervation.

    Science.gov (United States)

    Tudurí, Eva; Beiroa, Daniel; Stegbauer, Johannes; Fernø, Johan; López, Miguel; Diéguez, Carlos; Nogueiras, Rubén

    2016-11-01

    Pancreatic insulin-secreting β-cells express opioid receptors, whose activation by opioid peptides modulates hormone secretion. Opioid receptors are also expressed in multiple brain regions including the hypothalamus, where they play a role in feeding behavior and energy homeostasis, but their potential role in central regulation of glucose metabolism is unknown. Here, we investigate whether central opioid receptors participate in the regulation of insulin secretion and glucose homeostasis in vivo. C57BL/6J mice were acutely treated by intracerebroventricular (i.c.v.) injection with specific agonists for the three main opioid receptors, kappa (KOR), delta (DOR) and mu (MOR) opioid receptors: activation of KOR and DOR did not alter glucose tolerance, whereas activation of brain MOR with the specific agonist DAMGO blunted glucose-stimulated insulin secretion (GSIS), reduced insulin sensitivity, increased the expression of gluconeogenic genes in the liver and, consequently, impaired glucose tolerance. Pharmacological blockade of α2A-adrenergic receptors prevented DAMGO-induced glucose intolerance and gluconeogenesis. Accordingly, DAMGO failed to inhibit GSIS and to impair glucose tolerance in α2A-adrenoceptor knockout mice, indicating that the effects of central MOR activation on β-cells are mediated via sympathetic innervation. Our results show for the first time a new role of the central opioid system, specifically the MOR, in the regulation of insulin secretion and glucose metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Collateral Projections Innervate the Mammillary Bodies and Retrosplenial Cortex: A New Category of Hippocampal Cells

    Science.gov (United States)

    O’Mara, Shane M.

    2018-01-01

    To understand the hippocampus, it is necessary to understand the subiculum. Unlike other hippocampal subfields, the subiculum projects to almost all distal hippocampal targets, highlighting its critical importance for external networks. The present studies, in male rats and mice, reveal a new category of dorsal subiculum neurons that innervate both the mammillary bodies (MBs) and the retrosplenial cortex (RSP). These bifurcating neurons comprise almost half of the hippocampal cells that project to RSP. The termination of these numerous collateral projections was visualized within the medial mammillary nucleus and the granular RSP (area 29). These collateral projections included subiculum efferents that cross to the contralateral MBs. Within the granular RSP, the collateral projections form a particularly dense plexus in deep Layer II and Layer III. This retrosplenial termination site colocalized with markers for VGluT2 and neurotensin. While efferents from the hippocampal CA fields standardly collateralize, subiculum projections often have only one target site. Consequently, the many collateral projections involving the RSP and the MBs present a relatively unusual pattern for the subiculum, which presumably relates to how both targets have complementary roles in spatial processing. Furthermore, along with the anterior thalamic nuclei, the MBs and RSP are key members of a memory circuit, which is usually described as both starting and finishing in the hippocampus. The present findings reveal how the hippocampus simultaneously engages different parts of this circuit, so forcing an important revision of this network. PMID:29527569

  17. Innervation zone of the vastus medialis muscle: position and effect on surface EMG variables

    International Nuclear Information System (INIS)

    Gallina, A; Merletti, R; Gazzoni, M

    2013-01-01

    The aim of this study was to investigate the position of the innervation zone (IZ) of the vastus medialis (VM) and its effect on the electromyographic (EMG) amplitude and mean frequency estimates. Eighteen healthy subjects performed maximal isometric knee extensions at three knee angles. Surface EMG signals were collected by using a 16 × 8 electrode grid placed on the VM muscle. The position of the IZ was estimated through visual analysis, and traditional bipolar signals were obtained from channels over and away from it; amplitude and mean frequency values were extracted and compared using an analysis of variance (ANOVA) with repeated measures. The IZ is shaped as a line running from the proximal–lateral to the distal–medial aspect of the VM muscle. The presence of an IZ under the electrodes lowered the EMG amplitude (P < 0.001, F = 58.11) and increased the EMG mean frequency (P < 0.001, F = 26.47); variations of these parameters due to the knee flexion angle were less frequently observed in EMG signals collected over than away from the IZ. Electrodes placed ‘over the belly of the VM muscle’ are likely to collect EMG signals influenced by the presence of the IZ, thus hindering the detection of changes in muscle activity. (paper)

  18. Function and morphology correlates of rectal nerve mechanoreceptors innervating the guinea pig internal anal sphincter.

    Science.gov (United States)

    Lynn, P A; Brookes, S J H

    2011-01-01

    Mechanoreceptors to the internal anal sphincter (IAS) contribute to continence and normal defecation, yet relatively little is known about their function or morphology. We investigated the function and structure of mechanoreceptors to the guinea pig IAS. Extracellular recordings from rectal nerve branches to the IAS in vitro, combined with anterograde labeling of recorded nerve trunks, were used to characterize extrinsic afferent nerve endings activated by circumferential distension. Slowly adapting, stretch-sensitive afferents were recorded in rectal nerves to the IAS. Ten of 11 were silent under basal conditions and responded to circumferential stretch in a saturating linear manner. Rectal nerve afferents responded to compression with von Frey hairs with low thresholds (0.3-0.5 mN) and 3.4 ± 0.5 discrete, elongated mechanosensitive fields of innervation aligned parallel to circular muscle bundles (length = 62 ± 16 mm, n = 10). Anterogradely labeled rectal nerve axons typically passed through sparse irregular myenteric ganglia adjacent to the IAS, before ending in extensive varicose arrays within the circular muscle and, to a lesser extent, the longitudinal muscle overlying the IAS. Few (8%) IAS myenteric ganglia contained intraganglionic laminar endings. In eight preparations, mechanotransduction sites were mapped in combination with successful anterograde fills. Mechanotransduction sites were strongly associated with extensive fine varicose arrays within the circular muscle (P IAS are likely to correspond to extensive fine varicose arrays within the circular muscle. © 2010 Blackwell Publishing Ltd.

  19. Humans and great apes share increased neocortical neuropeptide Y innervation compared to other haplorhine primates

    Directory of Open Access Journals (Sweden)

    Mary Ann eRaghanti

    2014-02-01

    Full Text Available Neuropeptide Y (NPY plays a role in a variety of basic physiological functions and has also been implicated in regulating cognition, including learning and memory. A decrease in neocortical NPY has been reported for Alzheimer’s disease, schizophrenia, bipolar disorder, and depression, potentially contributing to associated cognitive deficits. The goal of the present analysis was to examine variation in neocortical NPY-immunoreactive axon and varicosity density among haplorhine primates (monkeys, apes, and humans. Stereologic methods were used to measure the ratios of NPY-expressing axon length density to total neuron density (ALv/Nv and NPY-immunoreactive varicosity density to neuron density (Vv/Nv, as well as the mean varicosity spacing in neocortical areas 10, 24, 44, and 22 (Tpt of humans, African great apes, New World monkeys, and Old World monkeys. Humans and great apes showed increased cortical NPY innervation relative to monkey species for ALv/Nv and Vv/Nv. Furthermore, humans and great apes displayed a conserved pattern of varicosity spacing across cortical areas and layers, with no differences between cortical layers or among cortical areas. These phylogenetic differences may be related to shared life history variables and may reflect specific cognitive abilities.

  20. Prolonged passive static stretching-induced innervation zone shift in biceps brachii.

    Science.gov (United States)

    Ye, Xin; Beck, Travis W; Wages, Nathan P

    2015-05-01

    The purpose of this study was to examine the influence of a bout of repeated and prolonged passive static stretching on the innervation zone (IZ) location of the human biceps brachii muscle. Eleven men performed 12 sets of 100-s passive stretches on their biceps brachii. Before (Pre) and immediately after (Post) the stretching intervention, isometric strength was tested during the maximal voluntary contractions (MVCs) of the forearm flexors. The subjects also performed several separate isometric forearm flexion muscle actions at 30%, 50%, and 70% of their predetermined MVCs for examining the locations of the IZ at different contraction intensities. The IZ was identified through multi-channel surface electromyographic (EMG) recordings from a linear electrode array. The stretching intervention induced an average of 10% isometric strength loss for the forearm flexors (mean±SD: Pre-MVC vs. Post-MVC=332.12±59.40 N vs. 299.53±70.51 N; p<0.001). In addition, the average IZ shift was nearly 4.5 mm in average in the proximal direction. However, this shift was not specific to the contraction intensity. We believe that the IZ shift was caused by the elongation of the entire muscle-tendon unit in the proximal direction. Therefore, caution should be taken when using surface EMG technique to examine possible changes in the EMG variables after a stretching protocol, as these variables can be contaminated by the shift of the IZ.

  1. Age-related synaptic loss of the medial olivocochlear efferent innervation

    Directory of Open Access Journals (Sweden)

    Schrader Angela

    2010-11-01

    Full Text Available Abstract Age-related functional decline of the nervous system is consistently observed, though cellular and molecular events responsible for this decline remain largely unknown. One of the most prevalent age-related functional declines is age-related hearing loss (presbycusis, a major cause of which is the loss of outer hair cells (OHCs and spiral ganglion neurons. Previous studies have also identified an age-related functional decline in the medial olivocochlear (MOC efferent system prior to age-related loss of OHCs. The present study evaluated the hypothesis that this functional decline of the MOC efferent system is due to age-related synaptic loss of the efferent innervation of the OHCs. To this end, we used a recently-identified transgenic mouse line in which the expression of yellow fluorescent protein (YFP, under the control of neuron-specific elements from the thy1 gene, permits the visualization of the synaptic connections between MOC efferent fibers and OHCs. In this model, there was a dramatic synaptic loss between the MOC efferent fibers and the OHCs in older mice. However, age-related loss of efferent synapses was independent of OHC status. These data demonstrate for the first time that age-related loss of efferent synapses may contribute to the functional decline of the MOC efferent system and that this synaptic loss is not necessary for age-related loss of OHCs.

  2. Adrenergic innervation of the developing chick heart: neural crest ablations to produce sympathetically aneural hearts

    International Nuclear Information System (INIS)

    Kirby, M.; Stewart, D.

    1984-01-01

    Ablation of various regions of premigratory trunk neural crest which gives rise to the sympathetic trunks was used to remove sympathetic cardiac innervation. Neuronal uptake of [ 3 H]-norepinephrine was used as an index of neuronal development in the chick atrium. Following ablation of neural crest over somites 10-15 or 15-20, uptake was significantly decreased in the atrium at 16 and 17 days of development. Ablation of neural crest over somites 5-10 and 20-25 caused no decrease in [ 3 H]-norepinephrine uptake. Removal of neural crest over somites 5-25 or 10-20 caused approximately equal depletions of [ 3 H]-norepinephrine uptake in the atrium. Cardiac norepinephrine concentration was significantly depressed following ablation of neural crest over somites 5-25 but not over somites 10-20. Light-microscopic and histofluorescent preparations confirmed the absence of sympathetic trunks in the region of the normal origin of the sympathetic cardiac nerves following neural crest ablation over somites 10-20. The neural tube and dorsal root ganglia were damaged in the area of the neural-crest ablation; however, all of these structures were normal cranial and caudal to the lesioned area. Development of most of the embryos as well as the morphology of all of the hearts was normal following the lesion. These results indicate that it is possible to produce sympathetically aneural hearts by neural-crest ablation; however, sympathetic cardiac nerves account for an insignificant amount of cardiac norepinephrine

  3. Selective pelvic autonomic nerve stimulation with simultaneous intraoperative monitoring of internal anal sphincter and bladder innervation.

    Science.gov (United States)

    Kneist, W; Kauff, D W; Koch, K P; Schmidtmann, I; Heimann, A; Hoffmann, K P; Lang, H

    2011-01-01

    Pelvic autonomic nerve preservation avoids postoperative functional disturbances. The aim of this feasibility study was to develop a neuromonitoring system with simultaneous intraoperative verification of internal anal sphincter (IAS) activity and intravesical pressure. 14 pigs underwent low anterior rectal resection. During intermittent bipolar electric stimulation of the inferior hypogastric plexus (IHP) and the pelvic splanchnic nerves (PSN), electromyographic signals of the IAS and manometry of the urinary bladder were observed simultaneously. Stimulation of IHP and PSN as well as simultaneous intraoperative monitoring could be realized with an adapted neuromonitoring device. Neurostimulation resulted in either bladder or IAS activation or concerted activation of both. Intravesical pressure increase as well as amplitude increase of the IAS neuromonitoring signal did not differ significantly between stimulation of IHP and PSN [6.0 cm H(2)O (interquartile range [IQR] 3.5-9.0) vs. 6.0 cm H(2)O (IQR 3.0-10.0) and 12.1 μV (IQR 3.0-36.7) vs. 40.1 μV (IQR 9.0-64.3)] (p > 0.05). Pelvic autonomic nerve stimulation with simultaneous intraoperative monitoring of IAS and bladder innervation is feasible. The method may enable neuromonitoring with increasing selectivity for pelvic autonomic nerve preservation. Copyright © 2011 S. Karger AG, Basel.

  4. Electrophysiology and Innervation of the Photosensitive Epistellar Body in the Lesser Octopus Eledone cirrhosa.

    Science.gov (United States)

    Cobb, C S; Williamson, R

    1998-08-01

    The innervation and responses to light of the cephalopod epistellar body were investigated in preparations isolated from the stellate ganglia of the lesser or northern octopus, Eledone cirrhosa. Extracellular generator potentials in response to flashes of light were recorded from these photosensitive vesicles, with the amplitude of the response being found to be dependent upon the intensity of the flash and the level of ambient illumination. Intracellular recordings from photoreceptor cells of the epistellar body showed that they had resting potentials of about -49 +/- 7 mV (mean +/- SD, n = 43) and were depolarized by flashes of white, but not red (>650 nm) light. The evoked depolarization consisted of a transient component, followed by a steady plateau in which the amplitude of the depolarization was well correlated with the log of the stimulus intensity. The evoked depolarizations induced action potentials in the photoreceptor cells, with the frequency of firing being well correlated with the stimulus intensity. The morphologies of individual photoreceptor cells were visualized by intracellular injections of the fluorescent dye Lucifer yellow, and the path of the epistellar nerve across the stellate ganglion, into the pallial nerve, toward the brain was traced using the lipophilic dye Di-I. This pathway was confirmed physiologically by recording light-evoked responses from the cut end of the pallial nerve.

  5. Conduction velocity is regulated by sodium channel inactivation in unmyelinated axons innervating the rat cranial meninges.

    Science.gov (United States)

    De Col, Roberto; Messlinger, Karl; Carr, Richard W

    2008-02-15

    Axonal conduction velocity varies according to the level of preceding impulse activity. In unmyelinated axons this typically results in a slowing of conduction velocity and a parallel increase in threshold. It is currently held that Na(+)-K(+)-ATPase-dependent axonal hyperpolarization is responsible for this slowing but this has long been equivocal. We therefore examined conduction velocity changes during repetitive activation of single unmyelinated axons innervating the rat cranial meninges. In direct contradiction to the currently accepted postulate, Na(+)-K(+)-ATPase blockade actually enhanced activity-induced conduction velocity slowing, while the degree of velocity slowing was curtailed in the presence of lidocaine (10-300 microm) and carbamazepine (30-500 microm) but not tetrodotoxin (TTX, 10-80 nm). This suggests that a change in the number of available sodium channels is the most prominent factor responsible for activity-induced changes in conduction velocity in unmyelinated axons. At moderate stimulus frequencies, axonal conduction velocity is determined by an interaction between residual sodium channel inactivation following each impulse and the retrieval of channels from inactivation by a concomitant Na(+)-K(+)-ATPase-mediated hyperpolarization. Since the process is primarily dependent upon sodium channel availability, tracking conduction velocity provides a means of accessing relative changes in the excitability of nociceptive neurons.

  6. Morphological study of the sensory innervation of the rat labial mucosa.

    Science.gov (United States)

    Yamamoto, T; Tazaki, M; Sakada, S

    1986-02-01

    The sensory innervation of the rat labial mucosa was investigated by means of methylene blue vital staining and osmic acid staining. Sensory receptors in this region were of three kinds (free nerve endings, encapsulated corpuscles and bush-like nerve endings) which constituted separate sensory units respectively. The encapsulated corpuscles were observed in the deep part of lamina propria, and distributed mainly in the margin of labial mucosa. Almost all (78.8%) of encapsulated corpuscles were of a simple type which had a non-branched axon terminal. No clew-like type corpuscles or glomerular-Meissner corpuscles were observed. The bush-like nerve endings were located in the lamina propria close to the epithelium, and localized in the central part of labial mucosa where the formation of papillae was remarkable. The density of the encapsulated corpuscles in the entire mucosa was 3.5-5.3/mm2, and that of the bush-like nerve endings in the densely distributed area was 38.9-60.6/mm2.

  7. Communication between corneal epithelial cells and trigeminal neurons is facilitated by purinergic (P2) and glutamatergic receptors.

    Science.gov (United States)

    Oswald, Duane J; Lee, Albert; Trinidad, Monique; Chi, Cheryl; Ren, Ruiyi; Rich, Celeste B; Trinkaus-Randall, Vickery

    2012-01-01

    Previously, we demonstrated that nucleotides released upon mechanical injury to corneal epithelium activate purinergic (P2) receptors resulting in mobilization of a Ca(2+) wave. However, the tissue is extensively innervated and communication between epithelium and neurons is critical and not well understood. Therefore, we developed a co-culture of primary trigeminal neurons and human corneal limbal epithelial cells. We demonstrated that trigeminal neurons expressed a repertoire of P2Yand P2X receptor transcripts and responded to P2 agonists in a concentration-dependent manner. Mechanical injuries to epithelia in the co-cultures elicited a Ca(2+) wave that mobilized to neurons and was attenuated by Apyrase, an ectonucleotidase. To elucidate the role of factors released from each cell type, epithelial and neuronal cells were cultured, injured, and the wound media from one cell type was collected and added to the other cell type. Epithelial wound media generated a rapid Ca(2+) mobilization in neuronal cells that was abrogated in the presence of Apyrase, while neuronal wound media elicited a complex response in epithelial cells. The rapid Ca(2+) mobilization was detected, which was abrogated with Apyrase, but it was followed by Ca(2+) waves that occurred in cell clusters. When neuronal wound media was preincubated with a cocktail of N-methyl-D-aspartate (NMDA) receptor inhibitors, the secondary response in epithelia was diminished. Glutamate was detected in the neuronal wound media and epithelial expression of NMDA receptor subunit transcripts was demonstrated. Our results indicate that corneal epithelia and neurons communicate via purinergic and NMDA receptors that mediate the wound response in a highly orchestrated manner.

  8. Communication between corneal epithelial cells and trigeminal neurons is facilitated by purinergic (P2 and glutamatergic receptors.

    Directory of Open Access Journals (Sweden)

    Duane J Oswald

    Full Text Available Previously, we demonstrated that nucleotides released upon mechanical injury to corneal epithelium activate purinergic (P2 receptors resulting in mobilization of a Ca(2+ wave. However, the tissue is extensively innervated and communication between epithelium and neurons is critical and not well understood. Therefore, we developed a co-culture of primary trigeminal neurons and human corneal limbal epithelial cells. We demonstrated that trigeminal neurons expressed a repertoire of P2Yand P2X receptor transcripts and responded to P2 agonists in a concentration-dependent manner. Mechanical injuries to epithelia in the co-cultures elicited a Ca(2+ wave that mobilized to neurons and was attenuated by Apyrase, an ectonucleotidase. To elucidate the role of factors released from each cell type, epithelial and neuronal cells were cultured, injured, and the wound media from one cell type was collected and added to the other cell type. Epithelial wound media generated a rapid Ca(2+ mobilization in neuronal cells that was abrogated in the presence of Apyrase, while neuronal wound media elicited a complex response in epithelial cells. The rapid Ca(2+ mobilization was detected, which was abrogated with Apyrase, but it was followed by Ca(2+ waves that occurred in cell clusters. When neuronal wound media was preincubated with a cocktail of N-methyl-D-aspartate (NMDA receptor inhibitors, the secondary response in epithelia was diminished. Glutamate was detected in the neuronal wound media and epithelial expression of NMDA receptor subunit transcripts was demonstrated. Our results indicate that corneal epithelia and neurons communicate via purinergic and NMDA receptors that mediate the wound response in a highly orchestrated manner.

  9. Aesthetic and Functional Outcomes of the Innervated and Thinned Anterolateral Thigh Flap in Reconstruction of Upper Limb Defects

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    Carlos Alberto Torres-Ortíz Zermeño

    2014-01-01

    Full Text Available Background. The anterolateral thigh (ALT flap has been widely described in reconstruction of the upper extremity. However, some details require refinement to improve both functional and aesthetic results. Methods. After reconstruction of upper extremity defects using thinned and innervated ALT flaps, functional and aesthetic outcomes were evaluated with the QuickDASH scale and a Likert scale for aesthetic assessment of free flaps, respectively. Results. Seven patients with a mean follow-up of 11.57 months and average flap thickness of 5 mm underwent innervation by an end-to-end neurorrhaphy. The average percentage of disability (QuickDASH was 21.88% with tenderness, pain, temperature, and two-point discrimination present in 100% of cases, and the aesthetic result gave an overall result of 15.40 (good with the best scores in color and texture. Conclusions. Simultaneous thinning and innervation of the ALT flap lead to a good cosmetic result and functional outcome with a low percentage of disability, which could result in minor surgical procedures and better recovery of motor and sensory function. Level of Evidence. IV.

  10. Does crossover innervation really affect the clinical outcome? A comparison of outcome between unilateral and bilateral digital nerve repair

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    Melike Oruç

    2016-01-01

    Full Text Available Digital nerve injuries are the mostly detected nerve injury in the upper extremity. However, since the clinical phenomenon of crossover innervation at some degree from uninjured digital nerve to the injured side occurs after digital nerve injuries is sustained, one could argue that this concept might even result in the overestimation of the outcome of the digital nerve repair. With this knowledge in mind, this study aimed to present novel, pure, focused and valuable clinical data by comparing the outcomes of bilateral and unilateral digital nerve repair. A retrospective review of 28 fingers with unilateral or bilateral digital nerve repair using end-to-end technique in 19 patients within 2 years was performed. Weber′s two-point discrimination, sharp/dull discrimination, warm/cold sensation and Visual Analog Scale scoring were measured at final 12-month follow ups in all patients. There was no significant difference in recovery of sensibility after unilateral and bilateral digital nerve repairs. Though there is crossover innervation microscopically, it is not important in the clinical evaluation period. According to clinical findings from this study, crossover innervations appear to be negligible in the estimation of outcomes of digital neurorrhaphy.

  11. Bergmann glia and the recognition molecule CHL1 organize GABAergic axons and direct innervation of Purkinje cell dendrites.

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    Fabrice Ango

    2008-04-01

    Full Text Available The geometric and subcellular organization of axon arbors distributes and regulates electrical signaling in neurons and networks, but the underlying mechanisms have remained elusive. In rodent cerebellar cortex, stellate interneurons elaborate characteristic axon arbors that selectively innervate Purkinje cell dendrites and likely regulate dendritic integration. We used GFP BAC transgenic reporter mice to examine the cellular processes and molecular mechanisms underlying the development of stellate cell axons and their innervation pattern. We show that stellate axons are organized and guided towards Purkinje cell dendrites by an intermediate scaffold of Bergmann glial (BG fibers. The L1 family immunoglobulin protein Close Homologue of L1 (CHL1 is localized to apical BG fibers and stellate cells during the development of stellate axon arbors. In the absence of CHL1, stellate axons deviate from BG fibers and show aberrant branching and orientation. Furthermore, synapse formation between aberrant stellate axons and Purkinje dendrites is reduced and cannot be maintained, leading to progressive atrophy of axon terminals. These results establish BG fibers as a guiding scaffold and CHL1 a molecular signal in the organization of stellate axon arbors and in directing their dendritic innervation.

  12. Biphasic regulation of development of the high-affinity saxitoxin receptor by innervation in rat skeletal muscle

    International Nuclear Information System (INIS)

    Sherman, S.J.; Catterall, W.A.

    1982-01-01

    Specific binding of 3 H-saxitoxin (STX) was used to quantitate the density of voltage-sensitive sodium channels in developing rat skeletal muscle. In adult triceps surae, a single class of sites with a KD . 2.9 nM and a density of 21 fmol/mg wet wt was detected. The density of these high-affinity sites increased from 2.0 fmol/mg wet wt to the adult value in linear fashion during days 2-25 after birth. Denervation of the triceps surae at day 11 or 17 reduced final saxitoxin receptor site density to 10.4 or 9.2 fmol/mg wet wt, respectively, without changing KD. Denervation of the triceps surae at day 5 did not alter the subsequent development of saxitoxin receptor sites during days 5-9 and accelerated the increase of saxitoxin receptor sites during days 9-13. After day 13, saxitoxin receptor development abruptly ceased and the density of saxitoxin receptor sites declined to 11 fmol/wg wet wt. These results show that the regulation of high-affinity saxitoxin receptor site density by innervation is biphasic. During the first phase, which is independent of continuing innervation, the saxitoxin receptor density increases to 47-57% of the adult level. After day 11, the second phase of development, which is dependent on continuing innervation, gives rise to the adult density of saxitoxin receptors

  13. The localization of primary efferent sympathetic neurons innervating the porcine thymus – a retrograde tracing study

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    Paweł Kulik

    2017-01-01

    Full Text Available The autonomic nervous system is a sophisticated and independent structure composed of two antagonistic (opposing divisions (sympathetic and parasympathetic that control many vital functions including: homeostasis maintenance, heart rate, blood circulation, secretion, etc. Thymus is one of the most important primary lymphoid organs playing a role in the developing of a juvenile’s immune system mainly by maturation, development, and migration of T-cells (T lymphocytes. In the last decades, several studies identifying sources of the thymic autonomic supply have been undertaken in humans and several laboratory rodents but not in higher mammals such as the pig. Therefore, in the present work, retrograde tracing technique of Fast Blue and DiI was used to investigate the sources of sympathetic efferent supply to the porcine thymus. After Fast Blue injection into the right lobe of the thymus, the presence of Fast Blue-positive neurons was found in the unilateral cranial cervical ganglion (82.8 ± 3.0% of total Fast Blue-positive neurons as well as in the middle cervical ganglion (17.2 ± 3.0%. Injection of DiI resulted in the presence of retrograde tracer in neurons of the cranial cervical ganglion (80.4 ± 2.3% of total amount of DiI-labelled neurons, the middle cervical ganglion (18.4 ± 1.9%, and the cervicothoracic ganglion (1.2 ± 0.8%. The present report provides the first data describing in details the localization of primary efferent sympathetic neurons innervating the porcine thymus.

  14. Prognostic value of sympathetic innervation and cardiac asynchrony in dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Manrique, Alain; Hitzel, Anne; Vera, Pierre; Bernard, Mathieu; Bauer, Fabrice; Menard, Jean-Francois; Sabatier, Remi; Jacobson, Arnold; Agostini, Denis

    2008-01-01

    The purpose of the study is to examine prognostic values of cardiac I-123 metaiodobenzylguanidine (MIBG) uptake and cardiac dyssynchrony in patients with dilated cardiomyopathy (DCM). Ninety-four patients with non-ischemic DCM underwent I-123 MIBG imaging for assessing cardiac sympathetic innervation and equilibrium radionuclide angiography. Mean phase angles and SD of the phase histogram were computed for both right ventricular (RV) and left ventricular (LV). Phase measures of interventricular (RV-LV) and intraventricular (SD-RV and SD-LV) asynchrony were computed. Most patients were receiving beta-blockers (89%) and angiotensin-converting enzyme inhibitors (88%). One patient (1%) was lost to follow-up, six had cardiac death (6.4%), eight had heart transplantation (8.6%), and seven had unplanned hospitalization for heart failure (7.5%; mean follow-up: 37 ± 16 months). Patients with poor clinical outcome were older, had higher The New York Heart Association functional class, impaired right ventricular ejection fraction and left ventricular ejection fraction, and impaired cardiac I-123 MIBG uptake. On multivariate analysis, I-123 MIBG heart-to-mediastinum (H/M) uptake ratio <1.6 was the only predictor of both primary (cardiac death or heart transplantation, RR = 7.02, p < 0.01) and secondary (cardiac death, heart transplantation, or recurrent heart failure, RR = 8.10, p = 0.0008) end points. In patients receiving modern medical therapy involving beta-blockers, I-123 MIBG uptake, but not intra-LV asynchrony, was predictive of clinical outcome. The impact of beta-blockers on the prognostic value of ventricular asynchrony remains to be clarified. (orig.)

  15. Effects of local cardiac denervation on cardiac innervation and ventricular arrhythmia after chronic myocardial infarction.

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    Xudong Liu

    Full Text Available Modulation of the autonomic nervous system (ANS has already been demonstrated to display antiarrhythmic effects in patients and animals with MI. In this study, we investigated whether local cardiac denervation has any beneficial effects on ventricular electrical stability and cardiac function in the chronic phase of MI.Twenty-one anesthetized dogs were randomly assigned into the sham-operated, MI and MI-ablation groups, respectively. Four weeks after local cardiac denervation, LSG stimulation was used to induce VPCs and VAs. The ventricular fibrillation threshold (VFT and the incidence of inducible VPCs were measured with electrophysiological protocol. Cardiac innervation was determined with immunohistochemical staining of growth associated protein-43 (GAP43 and tyrosine hydroxylase (TH. The global cardiac and regional ventricular function was evaluated with doppler echocardiography in this study.Four weeks after operation, the incidence of inducible VPC and VF in MI-ablation group were significantly reduced compared to the MI dogs (p<0.05. Moreover, local cardiac denervation significantly improved VFT in the infarcted border zone (p<0.05. The densities of GAP43 and TH-positive nerve fibers in the infarcted border zone in the MI-ablation group were lower than those in the MI group (p<0.05. However, the local cardiac denervation did not significantly improve cardiac function in the chronic phase of MI, determined by the left ventricle diameter (LV, left atrial diameter (LA, ejection fraction (EF.Summarily, in the chronic phase of MI, local cardiac denervation reduces the ventricular electrical instability, and attenuates spatial heterogeneity of sympathetic nerve reconstruction. Our study suggests that this methodology might decrease malignant ventricular arrhythmia in chronic MI, and has a great potential for clinical application.

  16. Hypothalamic vasopressinergic projections innervate central amygdala GABAergic neurons: implications for anxiety and stress coping

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    Vito Salvador Hernandez

    2016-11-01

    Full Text Available The arginine-vasopressin (AVP-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs are known for their role in hydro-electrolytic balance control via their projections to neurohypophysis. Recently, projections from these same neurons to hippocampus, habenula, and other brain regions, in which vasopressin infusion modulates contingent social and emotionally-affected behaviors, have been reported. Here, we present evidence that VPMNN collaterals also project to the amygdaloid complex, and establish synaptic connections with neurons in central amygdala (CeA. The density of AVP innervation in amygdala was substantially increased in adult rats that had experienced neonatal maternal separation (MS, consistent with our previous observations that MS enhances VPMNN number in the paraventricular (PVN and supraoptic (SON nuclei of the hypothalamus. In the CeA, V1a AVP receptor mRNA was only observed in GABAergic neurons, demonstrated by complete co-localization of V1a transcripts in neurons expressing Gad1 and Gad2 transcripts in CeA using the RNAscope method. V1b and V2 receptors mRNA were not detected, using the same method. Water-deprivation for 24 hrs, which increased the metabolic activity of VPMNNs, also increased anxiety-like behavior measured using the elevated plus maze test, and this effect was mimicked by bilateral microinfusion of VP into the CeA. Anxious behavior induced by either water deprivation or VP infusion was reversed by CeA infusion of V1a antagonist. VPMNNs are thus a newly discovered source of central amygdala inhibitory circuit modulation, through which both early-life and adult stress coping signals are conveyed from the hypothalamus to the amygdala.

  17. Cinematic innervation: the intuitive form of perception in the distracted perceptual field

    Directory of Open Access Journals (Sweden)

    Sungyong Ahn

    2013-09-01

    Full Text Available In “The Work of Art in the Age of Its Technological Reproducibility,” Walter Benjamin alluded that the human perceptual field in his time would become more distracted by the intervention of technologies, and so masses’ tactility activated by distraction would be more important in the mechanized perception. Regarding this historical situation, Benjamin anticipated that the new mode of mass perception would be organized through people's collective “innervation” to technologies. This article aims to contextualize this physiological term's cultural, technical, and political implications within various discourses about perception from the late 19th century physiologies to early 20th century film theories. Benjamin considers the tactility of people's potential to reconstruct the optical scheme of perception from the “flatness of screen” in which distances between viewers and perceived objects collapse. In a similar vein, the late 19th century's physiology reconceptualized perception in its relation not so much to the transcendental division of subject/object as to the sensual condition of a retina as “a single immanent plane.” From this perspective, perception is phenomena entailed by a body's contact to a sensual environment, so how sense inputs circulate in a neural network is a determinant for explaining perceptual processes. With regard to this paradigm change, the invention of cinema in the late 19th century was significant because it radically changed the composition of the perceptual field in two directions. Cinema introduced the virtualized perceptual fields on which sense circulations were completely controlled by the operation of camera. At the same time, the mediation of projectors in theaters reorganized viewers’ neural paths for perceptual innervation. As Hugo Münsterberg and Sergei Eisenstein's theories reflect, cinematic media's intervention in the perceptual field made it possible for masses’ collective

  18. Dynamic molecular imaging of cardiac innervation using a dual headpinhole SPECT system

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Jicun; Boutchko, Rostyslav; Sitek, Arkadiusz; Reutter, BryanW.; Huesman, Ronald H.; Gullberg, Grant T.

    2008-03-29

    Typically 123I-MIBG is used for the study of innervation andfunction of the sympathetic nervous system in heart failure. The protocolinvolves two studies: first a planar or SPECT scan is performed tomeasure initial uptake of the tracer, followed some 3-4 hours later byanother study measuring the wash-out of the tracer from the heart. A fastwash-out is indicative of a compromised heart. In this work, a dual headpinhole SPECT system was used for imaging the distribution and kineticsof 123I-MIBG in the myocardium of spontaneous hypertensive rats (SHR) andnormotensive Wistar Kyoto (WKY) rats. The system geometry was calibratedbased on a nonlinear point projection fitting method using a three-pointsource phantom. The angle variation effect of the parameters was modeledwith a sinusoidal function. A dynamic acquisition was performed byinjecting 123I-MIBG into rats immediately after starting the dataacquisition. The detectors rotated continuously performing a 360o dataacquisition every 90 seconds. We applied the factor analysis (FA)methodand region of interest (ROI) sampling method to obtain time activitycurves (TACs)in the blood pool and myocardium and then appliedtwo-compartment modeling to estimate the kinetic parameters. Since theinitial injection bolus is too fast for obtaining a consistenttomographic data set in the first few minutes of the study, we appliedthe FA method directly to projections during the first rotation. Then thetime active curves for blood and myocardial tissue were obtained from ROIsampling. The method was applied to determine if there were differencesin the kinetics between SHR and WKY rats and requires less time byreplacing the delayed scan at 3-4 hours after injection with a dynamicacquisition over 90 to 120 minutes. The results of a faster washout and asmaller distribution volume of 123IMIBG near the end of life in the SHRmodel of hypertrophic cardiomyopthy may be indicative of a failing heartin late stages of heart failure.

  19. Change in cell shape is required for matrix metalloproteinase-induced epithelial-mesenchymal transition of mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Celeste M.; Khauv, Davitte; Bissell, Mina J.; Radisky, Derek C.

    2008-06-26

    Cell morphology dictates response to a wide variety of stimuli, controlling cell metabolism, differentiation, proliferation, and death. Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells acquire migratory characteristics, and in the process convert from a 'cuboidal' epithelial structure into an elongated mesenchymal shape. We had shown previously that matrix metalloproteinase-3 (MMP3) can stimulate EMT of cultured mouse mammary epithelial cells through a process that involves increased expression of Rac1b, a protein that stimulates alterations in cytoskeletal structure. We show here that cells treated with MMP-3 or induced to express Rac1b spread to cover a larger surface, and that this induction of cell spreading is a requirement of MMP-3/Rac1b-induced EMT. We find that limiting cell spreading, either by increasing cell density or by culturing cells on precisely defined micropatterned substrata, blocks expression of characteristic markers of EMT in cells treated with MMP-3. These effects are not caused by general disruptions in cell signaling pathways, as TGF-{beta}-induced EMT is not affected by similar limitations on cell spreading. Our data reveal a previously unanticipated cell shape-dependent mechanism that controls this key phenotypic alteration and provide insight into the distinct mechanisms activated by different EMT-inducing agents.

  20. Visual Neurons in the Superior Colliculus Innervated by Islet2+ or Islet2− Retinal Ganglion Cells Display Distinct Tuning Properties

    Directory of Open Access Journals (Sweden)

    Rachel B. Kay

    2017-10-01

    Full Text Available Throughout the visual system, different subtypes of neurons are tuned to distinct aspects of the visual scene, establishing parallel circuits. Defining the mechanisms by which such tuning arises has been a long-standing challenge for neuroscience. To investigate this, we have focused on the retina’s projection to the superior colliculus (SC, where multiple visual neuron subtypes have been described. The SC receives inputs from a variety of retinal ganglion cell (RGC subtypes; however, which RGCs drive the tuning of different SC neurons remains unclear. Here, we pursued a genetic approach that allowed us to determine the tuning properties of neurons innervated by molecularly defined subpopulations of RGCs. In homozygous Islet2-EphA3 knock-in (Isl2EA3/EA3 mice, Isl2+ and Isl2− RGCs project to non-overlapping sub-regions of the SC. Based on molecular and anatomic data, we show that significantly more Isl2− RGCs are direction-selective (DS in comparison with Isl2+ RGCs. Targeted recordings of visual responses from each SC sub-region in Isl2EA3/EA3 mice revealed that Isl2− RGC-innervated neurons were significantly more DS than those innervated by Isl2+ RGCs. Axis-selective (AS neurons were found in both sub-regions, though AS neurons innervated by Isl2+ RGCs were more tightly tuned. Despite this segregation, DS and AS neurons innervated by Isl2+ or Isl2− RGCs did not differ in their spatial summation or spatial frequency (SF tuning. Further, we did not observe alterations in receptive field (RF size or structure of SC neurons innervated by Isl2+ or Isl2− RGCs. Together, these data show that innervation by Isl2+ and Isl2− RGCs results in distinct tuning in the SC and set the stage for future studies investigating the mechanisms by which these circuits are built.

  1. Force transmission in epithelial tissues.

    Science.gov (United States)

    Vasquez, Claudia G; Martin, Adam C

    2016-03-01

    In epithelial tissues, cells constantly generate and transmit forces between each other. Forces generated by the actomyosin cytoskeleton regulate tissue shape and structure and also provide signals that influence cells' decisions to divide, die, or differentiate. Forces are transmitted across epithelia because cells are mechanically linked through junctional complexes, and forces can propagate through the cell cytoplasm. Here, we review some of the molecular mechanisms responsible for force generation, with a specific focus on the actomyosin cortex and adherens junctions. We then discuss evidence for how these mechanisms promote cell shape changes and force transmission in tissues. © 2016 Wiley Periodicals, Inc.

  2. Central Somatosensory Networks Respond to a De Novo Innervated Penis: A Proof of Concept in Three Spina Bifida Patients.

    Science.gov (United States)

    Kortekaas, Rudie; Nanetti, Luca; Overgoor, Max L E; de Jong, Bauke M; Georgiadis, Janniko R

    2015-09-01

    Spina bifida (SB) causes low spinal lesions, and patients often have absent genital sensation and a highly impaired sex life. TOMAX (TO MAX-imize sensation, sexuality and quality of life) is a surgical procedure whereby the penis is newly innervated using a sensory nerve originally targeting the inguinal area. Most TOMAX-treated SB patients initially experience penile stimulation as inguinal sensation, but eventually, the perception shifts to penis sensation with erotic feelings. The brain mechanisms mediating this perceptual shift, which are completely unknown, could hold relevance for understanding the brain's role in sexual development. The aim of this study was to study how a newly perceived penis would be mapped onto the brain after a lifelong disconnection. Three TOMAX-treated SB patients participated in a functional magnetic resonance imagery experiment while glans penis, inguinal area, and index finger were stimulated with a paint brush. Brush stimulation-induced activation of the primary somatosensory cortex (SI) and functional connectivity between SI and remote cerebral regions. Stimulation of the re-innervated side of the glans penis and the intact contralateral inguinal area activated a very similar location on SI. Yet, connectivity analysis identified distinct SI functional networks. In all three subjects, the middle cingulate cortex (MCC) and the parietal operculum-insular cortex (OIC) were functionally connected to SI activity during glans penis stimulation, but not to SI activity induced by inguinal stimulation. Investigating central somatosensory network activity to a de novo innervated penis in SB patients is feasible and informative. The consistent involvement of MCC and OIC above and beyond the brain network expected on the basis of inguinal stimulation suggests that these areas mediate the novel penis sensation in these patients. The potential role of MCC and OIC in this process is discussed, along with recommendations for further research.

  3. Quantitation of cardiac sympathetic innervation in rabbits using 11C-hydroxyephedrine PET: relation to 123I-MIBG uptake

    International Nuclear Information System (INIS)

    Nomura, Yusuke; Kajinami, Kouji; Matsunari, Ichiro; Takamatsu, Hiroyuki; Murakami, Yoshihiro; Matsuya, Takahiro; Chen, Wei-Ping; Taki, Junichi; Nakajima, Kenichi; Nekolla, Stephan G.

    2006-01-01

    Although 11 C-hydroxyephedrine ( 11 C-HED) PET is used to map cardiac sympathetic innervation, no studies have shown the feasibility of quantitation of 11 C-HED PET in small- to medium-sized animals. Furthermore, its relation to 123 I-MIBG uptake, the most widely used sympathetic nervous tracer, is unknown. The aims of this study were to establish in vivo sympathetic nerve imaging in rabbits using 11 C-HED PET, and to compare the retention of 11 C-HED with that of 123 I-MIBG. Twelve rabbits were assigned to three groups; control (n=4), chemical denervation by 6-hydroxydopamine (6-OHDA) (n=4) and reserpine treated to inhibit vesicular uptake (n=4). After simultaneous injection of 11 C-HED and 123 I-MIBG, all animals underwent dynamic 11 C-HED PET for 40 min with arterial blood sampling. The 11 C-HED retention fraction and normalised 11 C-HED activity measured by tissue sampling were compared with those measured by PET. Both the 11 C-HED retention fraction and the normalised 11 C-HED activity measured by PET correlated closely with those measured by tissue sampling (R=0.96027, p 11 C-HED and 123 I-MIBG. Reserpine pretreatment reduced 11 C-HED retention by 50%, but did not reduce 123 I-MIBG retention at 40 min after injection. Non-invasive quantitation of cardiac sympathetic innervation using 11 C-HED PET is feasible and gives reliable estimates of cardiac sympathetic innervation in rabbits. Additionally, although both 11 C-HED and 123 I-MIBG are specific for sympathetic neurons, 11 C-HED may be more specific for intravesicular uptake than 123 I-MIBG in some situations, such as that seen in reserpine pretreatment. (orig.)

  4. Moderate caloric restriction during gestation in rats alters adipose tissue sympathetic innervation and later adiposity in offspring.

    Directory of Open Access Journals (Sweden)

    Ana Paula García

    Full Text Available Maternal prenatal undernutrition predisposes offspring to higher adiposity in adulthood. Mechanisms involved in these programming effects, apart from those described in central nervous system development, have not been established. Here we aimed to evaluate whether moderate caloric restriction during early pregnancy in rats affects white adipose tissue (WAT sympathetic innervation in the offspring, and its relationship with adiposity development. For this purpose, inguinal and retroperitoneal WAT (iWAT and rpWAT, respectively were analyzed in male and female offspring of control and 20% caloric-restricted (from 1-12 d of pregnancy (CR dams. Body weight (BW, the weight, DNA-content, morphological features and the immunoreactive tyrosine hydroxylase and Neuropeptide Y area (TH+ and NPY+ respectively, performed by immunohistochemistry of both fat depots, were studied at 25 d and 6 m of age, the latter after 2 m exposure to high fat diet. At 6 m of life, CR males but not females, exhibited greater BW, and greater weight and total DNA-content in iWAT, without changes in adipocytes size, suggesting the development of hyperplasia in this depot. However, in rpWAT, CR males but not females, showed larger adipocyte diameter, with no changes in DNA-content, suggesting the development of hypertrophy. These parameters were not different between control and CR animals at the age of 25 d. In iWAT, both at 25 d and 6 m, CR males but not females, showed lower TH(+ and NPY(+, suggesting lower sympathetic innervation in CR males compared to control males. In rpWAT, at 6 m but not at 25 d, CR males but not females, showed lower TH(+ and NPY(+. Thus, the effects of caloric restriction during gestation on later adiposity and on the differences in the adult phenotype between internal and subcutaneous fat depots in the male offspring may be associated in part with specific alterations in sympathetic innervation, which may impact on WAT architecture.

  5. "Fast" and "slow" skeleto-fusimotor innervation in cat tenuissimus spindles; a study with the glycogen-depletion method.

    Science.gov (United States)

    Jami, L; Lan-Couton, D; Malmgren, K; Petit, J

    1978-07-01

    The glycogen-depletion method was used to investigate the motor supply to tenuissimus with respect to the presence of fast beta axons and to assess the total proportion of both fast and slow beta-innervated spindles in this muscle. In a first series of 5 expts., groups of motor axons with conduction velocities higher than 85 m/s were repetitively stimulated so as to produce glycogen depletion in the muscle fibres they innervated. The whole muscle was then quick-frozen, serially cut, stained to demonstrate glycogen and examined for intrafusal glycogen depletion. Zones of glycogen depletion were found in 16 of the 46 examined spindles; they were most frequently located in the longest of the chain intrafusal muscle fibres. Since it is known that there are no purely fusimotor axons to tenuissimus with conduction velocities above 50 m/s, it was concluded that beta axons are present among the fastest axons to this muscle. In a second series of 5 expts. as many motor axons as possible with conduction velocities above 60 m/s were stimulated. Zones of glycogen depletion were found in 19 of the 47 examined spindles. They affected chain fibres in about half of the instances and bag1 fibers in the others. As this latter location is characteristic of slow dynamic beta axons, it was concluded that both slow and fast beta axons occur regularly in the motor supply to tenuissimus. beta-innervation is present in at least 40% of tenuissimus spindles with almost no convergence of fast and slow beta axons onto the same spindle.

  6. Developmental neurotoxicity targeting hepatic and cardiac sympathetic innervation: effects of organophosphates are distinct from those of glucocorticoids.

    Science.gov (United States)

    Seidler, Frederic J; Slotkin, Theodore A

    2011-05-30

    Early-life exposure to organophosphate pesticides leads to subsequent hyperresponsiveness of β-adrenergic receptor-mediated cell signaling that regulates hepatic gluconeogenesis, culminating in metabolic abnormalities resembling prediabetes. In the current study, we evaluated the effects of chlorpyrifos or parathion on presynaptic sympathetic innervation to determine whether the postsynaptic signaling effects are accompanied by defects in neuronal input. We administered either chlorpyrifos or parathion to newborn rats using exposure paradigms known to elicit the later metabolic changes but found no alterations in either hepatic or cardiac norepinephrine levels in adolescence or adulthood. However, shifting chlorpyrifos exposure to the prenatal period did evoke changes: exposure early in gestation produced subsequent elevations in norepinephrine, whereas later gestational exposure produced significant deficits. We also distinguished the organophosphate effects from those of the glucocorticoid, dexamethasone, a known endocrine disruptor that leads to later-life metabolic and cardiovascular disruption. Postnatal exposure to dexamethasone elicited deficits in peripheral norepinephrine levels but prenatal exposure did not. Our results indicate that early-life exposure to organophosphates leads to subsequent abnormalities of peripheral sympathetic innervation through mechanisms entirely distinct from those of glucocorticoids, ruling out the possibility that the organophosphate effects are secondary to stress or disruption of the HPA axis. Further, the effects on innervation were separable from those on postsynaptic signaling, differing in critical period as well as tissue- and sex-selectivity. Organophosphate targeting of both presynaptic and postsynaptic β-adrenergic sites, each with different critical periods of vulnerability, thus sets the stage for compounding of hepatic and cardiac functional abnormalities. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Regional and laminar distribution of the dopamine and serotonin innervation in the macaque cerebral cortex: a radioautographic study

    International Nuclear Information System (INIS)

    Berger, B.; Trottier, S.; Verney, C.; Gaspar, P.; Alvarez, C.

    1988-01-01

    The regional density and laminar distribution of dopamine (DA) and serotonin (5-HT) afferents were investigated in the cerebral cortex of cynomolgus monkeys using a radioautographic technique that is based on the high affinity uptake capacity of these aminergic neurons. Large vibratome sections, 50 micron thick, were incubated with [3H] DA (0.2 microM) and desipramine (5 microM) or with unlabeled norepinephrine (5 microM) and [3H] 5-HT (0.6 microM), which allowed for the specific labeling of the DA and 5-HT innervations, respectively. After fixation, these sections were dried, defatted, and radioautographed by dipping. Semiquantitative data on the DA innervation also were provided by counting [3H] DA-labeled axonal varicosities in radioautographs from 4-micron-thick sections of the slices obtained after epon embedding. The DA innervation was widespread and differed in density and laminar distribution in the agranular and granular cortices. DA afferents were densest in the anterior cingulate (area 24) and the motor areas (areas 4, 6, and supplementary motor area [SMA]). In the latter they displayed a trilaminar pattern of distribution, predominating in layers I, IIIa, and V-VI, with characteristic cluster-like formations in layer IIIa, especially in the medial part of motor areas. In the granular prefrontal (areas 46, 9, 10, 11, 12), parietal (areas 1, 2, 3, 5, 7), temporal (areas 21, 22), and posterior cingulate (area 23) cortices, DA afferents were less dense and showed a bilaminar pattern of distribution, predominating in the depth of layer I and in layers V-VI; density in layers II, III, and IV was only 20% of that in layer I. The lowest density was in the visual cortex, particularly in area 17, where the DA afferents were almost restricted to layer I

  8. Engineering epithelial-stromal interactions in vitro for toxicology assessment

    Science.gov (United States)

    Background: Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue function. Epithelial-mesenchymal interactions (EMIs) have been examined using mammalian models, ex vivo t...

  9. Epithelial Cells in Urine: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... page: https://medlineplus.gov/labtests/epithelialcellsinurine.html Epithelial Cells in Urine To use the sharing features on ... page, please enable JavaScript. What is an Epithelial Cells in Urine Test? Epithelial cells are a type ...

  10. An unbiased stereological method for efficiently quantifying the innervation of the heart and other organs based on total length estimations

    DEFF Research Database (Denmark)

    Mühlfeld, Christian; Papadakis, Tamara; Krasteva, Gabriela

    2010-01-01

    Quantitative information about the innervation is essential to analyze the structure-function relationships of organs. So far, there has been no unbiased stereological tool for this purpose. This study presents a new unbiased and efficient method to quantify the total length of axons in a given...... reference volume, illustrated on the left ventricle of the mouse heart. The method is based on the following steps: 1) estimation of the reference volume; 2) randomization of location and orientation using appropriate sampling techniques; 3) counting of nerve fiber profiles hit by a defined test area within...

  11. Localization of cholecystokininlike immunoreactivity in the rat spinal cord, with particular reference to the autonomic innervation of the pelvic organs

    DEFF Research Database (Denmark)

    Schrøder, H D

    1983-01-01

    tracing and immunocytochemistry revealed that the two cholecystokinin terminal fields characteristic for L1-L2 and that surrounding the intermediolateral nucleus in L6-S1 were situated corresponding to preganglionic neurons innervating pelvic organs through the hypogastric nerve or the pelvic nerves...... from the more cranial part with respect to type of afferent connections. The origin of the spinal cholecystokinin was investigated and it was found that neither complete transection of the spinal cord nor ipsilateral sectioning of three or four dorsal roots induced visible changes...

  12. Cholecystokinin (CCK)-expressing neurons in the suprachiasmatic nucleus: innervation, light responsiveness and entrainment in CCK-deficient mice

    DEFF Research Database (Denmark)

    Hannibal, Jens; Hundahl, Christian; Fahrenkrug, Jan

    2010-01-01

    FOS, and did not express the core clock protein PER1. Accordingly, CCK-deficient mice showed normal entrainment and had similar t, light-induced phase shift and negative masking behaviour as wild-type animals. In conclusion, CCK signalling seems not to be involved directly in light-induced resetting......, CCK-containing processes make synaptic contacts with both groups of neurons and some CCK cell bodies were innervated by VIPergic neurons. The CCK neurons received no direct input from the three major pathways to the SCN, and the CCK neurons were not light-responsive as evaluated by induction of c...

  13. Cholecystokinin (CCK)-expressing neurons in the suprachiasmatic nucleus: innervation, light responsiveness and entrainment in CCK-deficient mice

    DEFF Research Database (Denmark)

    Hannibal, Jens; Hundahl, Christian; Fahrenkrug, Jan

    2010-01-01

    FOS, and did not express the core clock protein PER1. Accordingly, CCK-deficient mice showed normal entrainment and had similar τ, light-induced phase shift and negative masking behaviour as wild-type animals. In conclusion, CCK signalling seems not to be involved directly in light-induced resetting......, CCK-containing processes make synaptic contacts with both groups of neurons and some CCK cell bodies were innervated by VIPergic neurons. The CCK neurons received no direct input from the three major pathways to the SCN, and the CCK neurons were not light-responsive as evaluated by induction of c...

  14. Dynamic molecular imaging of cardiac innervation using a dual head pinhole SPECT system

    International Nuclear Information System (INIS)

    Hu, Jicun; Boutchko, Rostyslav; Sitek, Arkadiusz; Reutter, BryanW.; Huesman, Ronald H.; Gullberg, Grant T.

    2008-01-01

    Typically 123I-MIBG is used for the study of innervation and function of the sympathetic nervous system in heart failure. The protocol involves two studies: first a planar or SPECT scan is performed to measure initial uptake of the tracer, followed some 3-4 hours later by another study measuring the wash-out of the tracer from the heart. A fast wash-out is indicative of a compromised heart. In this work, a dual head pinhole SPECT system was used for imaging the distribution and kinetics of 123I-MIBG in the myocardium of spontaneous hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. The system geometry was calibrated based on a nonlinear point projection fitting method using a three-point source phantom. The angle variation effect of the parameters was modeled with a sinusoidal function. A dynamic acquisition was performed by injecting 123I-MIBG into rats immediately after starting the data acquisition. The detectors rotated continuously performing a 360o data acquisition every 90 seconds. We applied the factor analysis (FA)method and region of interest (ROI) sampling method to obtain time activity curves (TACs)in the blood pool and myocardium and then applied two-compartment modeling to estimate the kinetic parameters. Since the initial injection bolus is too fast for obtaining a consistent tomographic data set in the first few minutes of the study, we applied the FA method directly to projections during the first rotation. Then the time active curves for blood and myocardial tissue were obtained from ROI sampling. The method was applied to determine if there were differences in the kinetics between SHR and WKY rats and requires less time by replacing the delayed scan at 3-4 hours after injection with a dynamic acquisition over 90 to 120 minutes. The results of a faster washout and a smaller distribution volume of 123I-MIBG near the end of life in the SHR model of hypertrophic cardiomyopthy may be indicative of a failing heart in late stages of heart

  15. Lymphocytes accelerate epithelial tight junction assembly: role of AMP-activated protein kinase (AMPK.

    Directory of Open Access Journals (Sweden)

    Xiao Xiao Tang

    2010-08-01

    Full Text Available The tight junctions (TJs, characteristically located at the apicolateral borders of adjacent epithelial cells, are required for the proper formation of epithelial cell polarity as well as for sustaining the mucosal barrier to the external environment. The observation that lymphocytes are recruited by epithelial cells to the sites of infection [1] suggests that they may play a role in the modulation of epithelial barrier function and thus contribute to host defense. To test the ability of lymphocytes to modulate tight junction assembly in epithelial cells, we set up a lymphocyte-epithelial cell co-culture system, in which Madin-Darby canine kidney (MDCK cells, a well-established model cell line for studying epithelial TJ assembly [2], were co-cultured with mouse lymphocytes to mimic an infection state. In a typical calcium switch experiment, the TJ assembly in co-culture was found to be accelerated compared to that in MDCK cells alone. This accelaration was found to be mediated by AMP-activated protein kinase (AMPK. AMPK activation was independent of changes in cellular ATP levels but it was found to be activated by the pro-inflammatory cytokine TNF-alpha. Forced suppression of AMPK, either with a chemical inhibitor or by knockdown, abrogated the accelerating effect of lymphocytes on TJ formation. Similar results were also observed in a co-culture with lymphocytes and Calu-3 human airway epithelial cells, suggesting that the activation of AMPK may be a general mechanism underlying lymphocyte-accelerated TJ assembly in different epithelia. These results suggest that signals from lymphocytes, such as cytokines, facilitate TJ assembly in epithelial cells via the activation of AMPK.

  16. Andrographolide suppresses epithelial mesenchymal transition by ...

    Indian Academy of Sciences (India)

    Epithelial mesenchymal transition (EMT) of lens epithelial cells (LECs) may contribute to the development of posterior capsular opacification (PCO), which leads to visual impairment. Andrographolide has been shown to have therapeutic potential against various cancers. However, its effect on human LECs is still unknown.

  17. Changes in the substance P-containing innervation of the lumbosacral spinal cord in male Wistar rats as a consequence of ageing.

    Science.gov (United States)

    Ranson, Richard N; Priestley, David J; Santer, Robert M; Watson, Alan H D

    2005-03-02

    Quantitative image analysis was used to determine age-related changes in the substance P-containing innervation of autonomic and somatic nuclei in the lumbosacral spinal cord, which are associated with the control of micturition and sexual reflexes. In the upper lumbar segments (L1-L2), significant declines in the distribution density of substance P-containing processes were observed in the dorsal grey commissure, the intermediolateral cell column and the ventral horn. More caudally, at levels corresponding to L5 through S1, significant reductions were seen in the dorsal grey commissure and within the sacral parasympathetic nucleus. In contrast to these observations, the substance P-immunoreactive innervation of the dorsolateral nucleus remained robust in aged animals and was not significantly different from young adults. It is possible that these distinct age-related patterns of change in substance P-containing innervation, are reflected in the urinary/sexual dysfunction's in aged animals.

  18. A region-specific quantitative profile of autonomic innervation of the canine left atrium and pulmonary veins.

    Science.gov (United States)

    Gao, Chong-han; Wang, Fei; Jiang, Rong; Zhang, Jin; Mou, Huamin; Yin, Yue-hui

    2011-07-05

    The aim of the present study was to determine and quantify the cardiac autonomic innervation of the canine atria and pulmonary vein. Tissue specimens were taken from the canine pulmonary veins (PVs), posterior left atrium (PLA), left atrial roof (LAR), anterior left atrium (ALA), interatrial septum (IAS), and left atrial appendage (LAA) respectively for immunohistochemical analysis and nerve density determination. Both sympathetic and parasympathetic nerve densities decreased in the order: PLA>PV>IAS>LAR>ALA>LAA. For sympathetic nerve, multiple comparisons between any two regions showed a significant difference (PIAS vs. LAR, and LAR vs. ALA; for parasympathetic nerve, all the differences between any pair of regions were statistically significant (PIAS vs. LAR, LAR vs. ALA, and ALA vs. LAA. For both nerve types, there was a decreasing gradient of nerve densities from the external to internal layer (P<0.001, for each comparisons). Nerve density at the ostia for either nerve type was significantly higher than at the distal segments of PVs (P<0.001). In summary, the LA and PVs are innervated by sympathetic and parasympathetic nerves in a regionally heterogeneous way, which may be important for the pathophysiological investigation and ablation therapy of atrial fibrillation (AF). Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Morfofisiologia da inervação do diafragma de ovinos Morphophysiology of diaphragm innervation in sheep

    Directory of Open Access Journals (Sweden)

    Ana E.F. de Almeida

    2008-09-01

    Full Text Available Foram estudados em 30 diafragmas de ovinos da raça Santa Inês, a origem, a divisão e a distribuição dos nervos frênicos direito e esquerdo (Fde e a participação de outros nervos na inervação do diafragma. Mediante fixação e dissecação das peças foi observado que os nervos frênicos (F originam-se a partir dos ramos ventrais do 5º (C5 e 6º (C6 nervos espinhais cervicais (Ec tanto à direita (46,67% como à esquerda (43,33%. Os F finalizam em tronco lombocostal e ramo esternal à direita (40,00% e em ramo lombar, costal e esternal à esquerda (36,68%. Os ramos lombares dos F inervam à esquerda (96,67% o pilar homolateral do diafragma e, à direita (50,00% fornecem filetes à veia caudal. Os ramos costais dos F ramificam à esquerda (90,00% e à direita (76,67% as regiões dorsal e ventral da pars costalis. Os ramos esternais dos F inervam à direita (100,00% e à esquerda (83,33% a pars sternalis e a região ventral da pars costalis do mesmo lado. Os nervos intercostais (VIII ao XII pares, 63,33% contribuem na inervação do diafragma de ovinos da raça Santa Inês.Thirty diaphragms of sheep of Santa Inês breed were studied regarding their origin, division and arrangement of the right and left phrenic nerves (Fde, and the participation of other nerves in the innervation of the diaphragm. By fixing and dissecting pieces, it was found that phrenic nerves (F frequently come from the ventral branches of the 5th (C5 and 6th (C6 cervical spinal nerves (Ec, at right (46.67% and at left (43.33%. The F often form a lumbocostal trunk, sternal branches at right (40.00% and lumbar, costal and esternal branches at left (36.68%. The lumbar branches of F innervate frequently at left (96.67% the homolateral pillar of the diaphragma, and at right (50.00% they give fillets to Vena cava caudalis. The costal branches of the F innervate at left (90.00% and at right (76.66% the dorsal and ventral regions of the pars costalis. The sternal branches of

  20. For Vol.67, No.5 pp325-331 Phalloplasty with an Innervated Island Pedicled Anterolateral Thigh Flap in a Female-to-Male Transsexual

    OpenAIRE

    Hasegawa, Kenjiro; Namba, Yuzaburo; Kimata, Yoshihiro

    2014-01-01

    Since 2001, we have been performing phalloplasty with a radial forearm free flap as the flap of firstchoice in female-to-male transsexuals (FTMTS). In the present case, a 22-year-old FTMTS with anegative Allen test, we achieved good results by performing phalloplasty with an innervated islandpedicled anterolateral thigh flap using the “tube within a tube” technique, in which the penis and urethraare constructed with a single flap. As compared to a forearm flap, use of an innervated islandpedi...

  1. Patterning bacterial communities on epithelial cells.

    Directory of Open Access Journals (Sweden)

    Mohammed Dwidar

    Full Text Available Micropatterning of bacteria using aqueous two phase system (ATPS enables the localized culture and formation of physically separated bacterial communities on human epithelial cell sheets. This method was used to compare the effects of Escherichia coli strain MG1655 and an isogenic invasive counterpart that expresses the invasin (inv gene from Yersinia pseudotuberculosis on the underlying epithelial cell layer. Large portions of the cell layer beneath the invasive strain were killed or detached while the non-invasive E. coli had no apparent effect on the epithelial cell layer over a 24 h observation period. In addition, simultaneous testing of the localized effects of three different bacterial species; E. coli MG1655, Shigella boydii KACC 10792 and Pseudomonas sp DSM 50906 on an epithelial cell layer is also demonstrated. The paper further shows the ability to use a bacterial predator, Bdellovibriobacteriovorus HD 100, to selectively remove the E. coli, S. boydii and P. sp communities from this bacteria-patterned epithelial cell layer. Importantly, predation and removal of the P. Sp was critical for maintaining viability of the underlying epithelial cells. Although this paper focuses on a few specific cell types, the technique should be broadly applicable to understand a variety of bacteria-epithelial cell interactions.

  2. Slow-tonic muscle fibers and their potential innervation in the turtle, Pseudemys (Trachemys) scripta elegans.

    Science.gov (United States)

    Callister, Robert J; Pierce, Patricia A; McDonagh, Jennifer C; Stuart, Douglas G

    2005-04-01

    fiber type, with the distribution of slow-tonic fibers paralleling that of the SO fibers. In the five test muscles, fiber cross-sectional area was usually ranked Fg > FOG > SO, and slow-twitch always > slow-tonic. In terms of weighted cross-sectional area, which provides a coarse-grain measure of each fiber type's potential contribution to whole muscle force, all five muscles exhibited a higher Fg and lower SO contribution to cross-sectional area than suggested by their corresponding fiber-type prevalence. This was also the case for the slow-twitch vs. slow-tonic fibers. We conclude that slow-tonic fibers are widespread in turtle muscle. The weighted cross-sectional area evidence suggested, however, that their contribution to force generation is minor except in highly oxidative muscles, with a special functional role, like TeC4. There is discussion of: 1) the relationship between the present results and previous work on homologous neck and hindlimb muscles in other nonmammalian species, and 2) the potential motoneuronal innervation of slow-tonic fibers in turtle hindlimb muscles. Copyright 2005 Wiley-Liss, Inc.

  3. Clinical and pathological aspects of epithelial hyperplasia.

    Science.gov (United States)

    Gîrtan, Mihaela; Stăniceanu, Florica; Zurac, Sabina; Laba, Elisabeta; Forna, Norina

    2008-01-01

    In many cases, the oral health status indicates the general status of the body. 90% of the disorders of the body also manifest at the level of the oral cavity, which means that the dentist can draw the attention of a certain health problem. Diabetes mellitus is associated with a high prevalence of the lesions of the oral mucous, especially lichen planus, recurrent aphthous stomatitis or oral candidiasis. We present here a case of diabetes mellitus with hyperplasic lesion at the level of the inferior vestibule, extended to the right jugal mucosa. The lesion appeared pursuant to the application of removable prosthetics. The biopsy specimen was examined using normal and special staining (HE Hematoxiline - eosine, Van Gieson VG) and immunohistochemistry (IHC). In the HE stain, an epithelial hyperplasia was noticed as a result of the proliferation of the basal cells, associated with hyperkeratosis (parakeratosis or orthokeratosis). A moderated inflammatory limphoplasmocitary infiltrate, composed by lymphocytes and plasma cells, was present within the hyperplasic chorion. The immunohistochemical reactions revealed Ki-67 positive nuclei in the basal and suprabasal strata (indicating an increased proliferating activity); rare p53 positive nuclei in the basal stratum (indicating a suppressive action on the cell proliferation); CD3/CD8 positive cells in the inflammatory infiltrate (indicating an important number of T suppressor lymphocytes in the inflammatory infiltrate). In conclusion, diabetes mellitus is a disease which frequently determines major modifications at the level of the oral cavity. Interdisciplinary collaboration between the pathologist and the dentist is necessary for adequate diagnosis and successful treatment.

  4. MRI appearances of pure epithelial papillary serous borderline ovarian tumours

    International Nuclear Information System (INIS)

    Naqvi, J.; Nagaraju, E.; Ahmad, S.

    2015-01-01

    Borderline epithelial ovarian tumours (BOT) represent 15–20% of all non-benign ovarian epithelial neoplasms. Compared to malignant ovarian tumours, they usually present at a younger age and carry a far superior prognosis. Fertility-conserving surgery is an important treatment option for patients with BOT. Ultrasound and CT are both widely available and play roles in the initial investigation and staging of BOT, respectively. However, lack of soft-tissue contrast limits their ability to characterize BOT. MRI can facilitate recognition of pure epithelial serous BOT (SBOT), including the cystic papillary and surface papillary subtypes. An abundance of hyperintense papillary projections with low signal internal branching and ovarian stroma preservation with a hypointense ovarian capsular margin on T2-weighted imaging are features strongly suggestive of SBOT. In this review we will discuss the general morphological features of SBOT, the benefits and drawbacks of ultrasound and CT in the initial work-up, and the principal MRI features enabling recognition of surface papillary and cystic papillary SBOT

  5. Basolateral BMP signaling in polarized epithelial cells.

    Directory of Open Access Journals (Sweden)

    Masao Saitoh

    Full Text Available Bone morphogenetic proteins (BMPs regulate various biological processes, mostly mediated by cells of mesenchymal origin. However, the roles of BMPs in epithelial cells are poorly understood. Here, we demonstrate that, in polarized epithelial cells, BMP signals are transmitted from BMP receptor complexes exclusively localized at the basolateral surface of the cell membrane. In addition, basolateral stimulation with BMP increased expression of components of tight junctions and enhanced the transepithelial resistance (TER, counteracting reduction of TER by treatment with TGF-β or an anti-tumor drug. We conclude that BMPs maintain epithelial polarity via intracellular signaling from basolaterally localized BMP receptors.

  6. Membrane lipidome of an epithelial cell line

    DEFF Research Database (Denmark)

    Sampaio, Julio L; Gerl, Mathias J; Klose, Christian

    2011-01-01

    Tissue differentiation is an important process that involves major cellular membrane remodeling. We used Madin-Darby canine kidney cells as a model for epithelium formation and investigated the remodeling of the total cell membrane lipidome during the transition from a nonpolarized morphology...... to an epithelial morphology and vice versa. To achieve this, we developed a shotgun-based lipidomics workflow that enabled the absolute quantification of mammalian membrane lipidomes with minimal sample processing from low sample amounts. Epithelial morphogenesis was accompanied by a major shift from sphingomyelin...... to generate an apical membrane domain that serves as a protective barrier for the epithelial sheet....

  7. Epithelial cell polarity, stem cells and cancer

    DEFF Research Database (Denmark)

    Martin-Belmonte, Fernando; Perez-Moreno, Mirna

    2011-01-01

    , deregulation of adhesion and polarity proteins can cause misoriented cell divisions and increased self-renewal of adult epithelial stem cells. In this Review, we highlight some advances in the understanding of how loss of epithelial cell polarity contributes to tumorigenesis.......After years of extensive scientific discovery much has been learned about the networks that regulate epithelial homeostasis. Loss of expression or functional activity of cell adhesion and cell polarity proteins (including the PAR, crumbs (CRB) and scribble (SCRIB) complexes) is intricately related...

  8. Cadherin-13 Deficiency Increases Dorsal Raphe 5-HT Neuron Density and Prefrontal Cortex Innervation in the Mouse Brain

    Directory of Open Access Journals (Sweden)

    Andrea Forero

    2017-09-01

    Full Text Available Background: During early prenatal stages of brain development, serotonin (5-HT-specific neurons migrate through somal translocation to form the raphe nuclei and subsequently begin to project to their target regions. The rostral cluster of cells, comprising the median and dorsal raphe (DR, innervates anterior regions of the brain, including the prefrontal cortex. Differential analysis of the mouse 5-HT system transcriptome identified enrichment of cell adhesion molecules in 5-HT neurons of the DR. One of these molecules, cadherin-13 (Cdh13 has been shown to play a role in cell migration, axon pathfinding, and synaptogenesis. This study aimed to investigate the contribution of Cdh13 to the development of the murine brain 5-HT system.Methods: For detection of Cdh13 and components of the 5-HT system at different embryonic developmental stages of the mouse brain, we employed immunofluorescence protocols and imaging techniques, including epifluorescence, confocal and structured illumination microscopy. The consequence of CDH13 loss-of-function mutations on brain 5-HT system development was explored in a mouse model of Cdh13 deficiency.Results: Our data show that in murine embryonic brain Cdh13 is strongly expressed on 5-HT specific neurons of the DR and in radial glial cells (RGCs, which are critically involved in regulation of neuronal migration. We observed that 5-HT neurons are intertwined with these RGCs, suggesting that these neurons undergo RGC-guided migration. Cdh13 is present at points of intersection between these two cell types. Compared to wildtype controls, Cdh13-deficient mice display increased cell densities in the DR at embryonic stages E13.5, E17.5, and adulthood, and higher serotonergic innervation of the prefrontal cortex at E17.5.Conclusion: Our findings provide evidence for a role of CDH13 in the development of the serotonergic system in early embryonic stages. Specifically, we indicate that Cdh13 deficiency affects the cell

  9. Subacute cardiac sympathetic dys-innervation, evaluated by the tomo-scintigraphy with {sup 123}I-Mibg in the Takotsubo syndrome: about one case; Dysinnervation sympathique cardiaque subaigue, evaluee par la tomoscintigraphie a l'123I-MIBG dans le syndrome de Takotsubo: a propos d'un cas

    Energy Technology Data Exchange (ETDEWEB)

    Costo, S.; Agostini, D. [Service de medecine nucleaire, CHU Cote-de-Nacre, Caen, (France); Sabatier, R. [service de cardiologie, CHU Cote-de-Nacre, Caen, (France)

    2009-05-15

    The association of perfusion imaging and myocardium innervation showed a major mismatch of fixation attesting of a sympathetic default of innervation contemporary of a left ventricle dysfunction without perfusion troubles, for a patient with a Takotsubo cardiomyopathy. (N.C.)

  10. Andrographolide suppresses epithelial mesenchymal transition by ...

    Indian Academy of Sciences (India)

    2015-04-27

    Apr 27, 2015 ... by inhibition of MAPK signalling pathway in lens epithelial cells. FORUM KAYASTHA ... 1Iladevi Cataract and IOL Research Centre, Gurukul road, Memnagar, Ahmedabad 380 052, India ...... sition and the stem cell phenotype.

  11. Thymic epithelial cells. I. Expression of strong suppressive (veto) activity in mouse thymic epithelial cell cultures

    DEFF Research Database (Denmark)

    Claesson, Mogens Helweg; Ropke, C

    1990-01-01

    We show that thymic epithelial cells grown under serum-free conditions in a chemically defined culture medium can act as veto cells in vitro. The veto activity of thymic epithelial cells results in inactivation of specific alloreactive cytotoxic T-cell precursors at the clonal level. It is conclu......We show that thymic epithelial cells grown under serum-free conditions in a chemically defined culture medium can act as veto cells in vitro. The veto activity of thymic epithelial cells results in inactivation of specific alloreactive cytotoxic T-cell precursors at the clonal level...

  12. DNA repair in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Fornace, A.J. Jr.; Lechner, J.F.; Grafstrom, R.C.; Harris, C.C.

    1982-01-01

    The purpose of this investigation was to compare the response of human cell types (bronchial epithelial cells and fibroblasts and skin fibroblasts) to various DNA damaging agents. Repair of DNA single strand breaks (SSB) induced by 5 krads of X-ray was similar for all cell types; approximately 90% of the DNA SSB were rejoined within one hour. During excision repair of DNA damage from u.v.-radiation, the frequencies of DNA SSB as estimated by the alkaline elution technique, were similar in all cell types. Repair replication as measured by BND cellulose chromatography was also similar in epithelial and fibroblastic cells after u.v.-irradiation. Similar levels of SSB were also observed in epithelial and fibroblastic cells after exposure to chemical carcinogens: 7,12-dimethylbenz[a]anthracene; benzo[a]pyrene diol epoxide (BPDE); or N-methyl-N-nitro-N-nitrosoguanidine. Significant repair replication of BPDE-induced DNA damage was detected in both bronchial epithelial and fibroblastic cells, although the level in fibroblasts was approximately 40% of that in epithelial cells. The pulmonary carcinogen asbestos did not damage DNA. DNA-protein crosslinks induced by formaldehyde were rapidly removed in bronchial cells. Further, epithelial and fibroblastic cells, which were incubated with formaldehyde and the polymerase inhibitor combination of cytosine arabinoside and hydroxyurea, accumulated DNA SSB at approximately equal frequencies. These results should provide a useful background for further investigations of the response of human bronchial cells to various DNA damaging agents

  13. Dorsal root ganglion neurons innervating skeletal muscle respond to physiological combinations of protons, ATP, and lactate mediated by ASIC, P2X, and TRPV1.

    Science.gov (United States)

    Light, Alan R; Hughen, Ronald W; Zhang, Jie; Rainier, Jon; Liu, Zhuqing; Lee, Jeewoo

    2008-09-01

    The adequate stimuli and molecular receptors for muscle metaboreceptors and nociceptors are still under investigation. We used calcium imaging of cultured primary sensory dorsal root ganglion (DRG) neurons from C57Bl/6 mice to determine candidates for metabolites that could be the adequate stimuli and receptors that could detect these stimuli. Retrograde DiI labeling determined that some of these neurons innervated skeletal muscle. We found that combinations of protons, ATP, and lactate were much more effective than individually applied compounds for activating rapid calcium increases in muscle-innervating dorsal root ganglion neurons. Antagonists for P2X, ASIC, and TRPV1 receptors suggested that these three receptors act together to detect protons, ATP, and lactate when presented together in physiologically relevant concentrations. Two populations of muscle-innervating DRG neurons were found. One responded to low metabolite levels (likely nonnoxious) and used ASIC3, P2X5, and TRPV1 as molecular receptors to detect these metabolites. The other responded to high levels of metabolites (likely noxious) and used ASIC3, P2X4, and TRPV1 as their molecular receptors. We conclude that a combination of ASIC, P2X5 and/or P2X4, and TRPV1 are the molecular receptors used to detect metabolites by muscle-innervating sensory neurons. We further conclude that the adequate stimuli for muscle metaboreceptors and nociceptors are combinations of protons, ATP, and lactate.

  14. Application of a New Robust ECG T-Wave Delineation Algorithm for the Evaluation of the Autonomic Innervation of the Myocardium

    DEFF Research Database (Denmark)

    Cesari, Matteo; Mehlsen, Jesper; Mehlsen, Anne-Birgitte

    2016-01-01

    T-wave amplitude (TWA) is a well know index of the autonomic innervation of the myocardium. However, until now it has been evaluated only manually or with simple and inefficient algorithms. In this paper, we developed a new robust single-lead electrocardiogram (ECG) T-wave delineation algorithm...

  15. Spatiotemporal dynamics of re-innervation and hyperinnervation patterns by uninjured CGRP fibers in the rat foot sole epidermis after nerve injury

    NARCIS (Netherlands)

    L.S. Duraku (Liron); S.M. Hossaini (Mehdi); S. Hoendervangers (Sieske); H.E. Falke; S. Kambiz (Shoista); V. Mudera (Vivek); J.C. Holstege (Jan); E.T. Walbeehm (Erik); T.J.H. Ruigrok (Tom)

    2012-01-01

    textabstractThe epidermis is innervated by fine nerve endings that are important in mediating nociceptive stimuli. However, their precise role in neuropathic pain is still controversial. Here, we have studied the role of epidermal peptidergic nociceptive fibers that are located adjacent to injured

  16. Pox neuro control of cell lineages that give rise to larval poly-innervated external sensory organs in Drosophila.

    Science.gov (United States)

    Jiang, Yanrui; Boll, Werner; Noll, Markus

    2015-01-15

    The Pox neuro (Poxn) gene of Drosophila plays a crucial role in the development of poly-innervated external sensory (p-es) organs. However, how Poxn exerts this role has remained elusive. In this study, we have analyzed the cell lineages of all larval p-es organs, namely of the kölbchen, papilla 6, and hair 3. Surprisingly, these lineages are distinct from any previously reported cell lineages of sensory organs. Unlike the well-established lineage of mono-innervated external sensory (m-es) organs and a previously proposed model of the p-es lineage, we demonstrate that all wild-type p-es lineages exhibit the following features: the secondary precursor, pIIa, gives rise to all three support cells-socket, shaft, and sheath, whereas the other secondary precursor, pIIb, is neuronal and gives rise to all neurons. We further show that in one of the p-es lineages, that of papilla 6, one cell undergoes apoptosis. By contrast in Poxn null mutants, all p-es lineages have a reduced number of cells and their pattern of cell divisions is changed to that of an m-es organ, with the exception of a lineage in a minority of mutant kölbchen that retains a second bipolar neuron. Indeed, the role of Poxn in p-es lineages is consistent with the specification of the developmental potential of secondary precursors and the regulation of cell division but not apoptosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Distribution and innervation of putative peripheral arterial chemoreceptors in the red-eared slider (Trachemys scripta elegans).

    Science.gov (United States)

    Reyes, Catalina; Fong, Angelina Y; Milsom, William K

    2015-06-15

    Peripheral arterial chemoreceptors have been isolated to the common carotid artery, aorta, and pulmonary artery of turtles. However, the putative neurotransmitters associated with these chemoreceptors have not yet been described. The goal of the present study was to determine the neurochemical content, innervations, and distribution of putative oxygen-sensing cells in the central vasculature of turtles and to derive homologies with peripheral arterial chemoreceptors of other vertebrates. We used tract tracing together with immunohistochemical markers for cholinergic cells (vesicular acetylcholine transporter [VAChT]), tyrosine hydroxylase (TH; the rate-limiting enzyme in catecholamine synthesis), and serotonin (5HT) to identify putative oxygen-sensing cells and to determine their anatomical relation to branches of the vagus nerve (Xth cranial nerve). We found potential oxygen-sensing cells in all three chemosensory areas innervated by branches of the Xth cranial nerve. Cells containing either 5HT or VAChT were found in all three sites. The morphology and size of these cells resemble glomus cells found in amphibians, mammals, tortoises, and lizards. Furthermore, we found populations of cholinergic cells located at the base of the aorta and pulmonary artery that are likely involved in efferent regulation of vessel resistance. Catecholamine-containing cells were not found in any of the putative chemosensitive areas. The presence of 5HT- and VAChT-immunoreactive cells in segments of the common carotid artery, aorta, and pulmonary artery appears to reflect a transition between cells containing the major neurotransmitters seen in fish (5HT) and mammals (ACh and adenosine). © 2015 Wiley Periodicals, Inc.

  18. Anterograde Tracing Method using DiI to Label Vagal Innervation of the Embryonic and Early Postnatal Mouse Gastrointestinal Tract

    Science.gov (United States)

    Murphy, Michelle C.; Fox, Edward A.

    2007-01-01

    The mouse is an extremely valuable model for studying vagal development in relation to strain differences, genetic variation, gene manipulations, or pharmacological manipulations. Therefore, a method using 1, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) was developed for labeling vagal innervation of the gastrointestinal (GI) tract in embryonic and postnatal mice. DiI labeling was adapted and optimized for this purpose by varying several facets of the method. For example, insertion and crushing of DiI crystals into the nerve led to faster DiI diffusion along vagal axons and diffusion over longer distances as compared with piercing the nerve with a micropipette tip coated with dried DiI oil. Moreover, inclusion of EDTA in the fixative reduced leakage of DiI out of nerve fibers that occurred with long incubations. Also, mounting labeled tissue in PBS was superior to glycerol with n-propyl gallate, which resulted in reduced clarity of DiI labeling that may have been due to DiI leaking out of fibers. Optical sectioning of flattened wholemounts permitted examination of individual tissue layers of the GI tract wall. This procedure aided identification of nerve ending types because in most instances each type innervates a different tissue layer. Between embryonic day 12.5 and postnatal day 8, growth of axons into the GI tract, formation and patterning of fiber bundles in the myenteric plexus and early formation of putative afferent and efferent nerve terminals were observed. Thus, the DiI tracing method developed here has opened up a window for investigation during an important phase of vagal development. PMID:17418900

  19. Cutaneous collateral axonal sprouting re-innervates the skin component and restores sensation of denervated Swine osteomyocutaneous alloflaps.

    Directory of Open Access Journals (Sweden)

    Zuhaib Ibrahim

    Full Text Available Reconstructive transplantation such as extremity and face transplantation is a viable treatment option for select patients with devastating tissue loss. Sensorimotor recovery is a critical determinant of overall success of such transplants. Although motor function recovery has been extensively studied, mechanisms of sensory re-innervation are not well established. Recent clinical reports of face transplants confirm progressive sensory improvement even in cases where optimal repair of sensory nerves was not achieved. Two forms of sensory nerve regeneration are known. In regenerative sprouting, axonal outgrowth occurs from the transected nerve stump while in collateral sprouting, reinnervation of denervated tissue occurs through growth of uninjured axons into the denervated tissue. The latter mechanism may be more important in settings where transected sensory nerves cannot be re-apposed. In this study, denervated osteomyocutaneous alloflaps (hind- limb transplants from Major Histocompatibility Complex (MHC-defined MGH miniature swine were performed to specifically evaluate collateral axonal sprouting for cutaneous sensory re-innervation. The skin component of the flap was externalized and serial skin sections extending from native skin to the grafted flap were biopsied. In order to visualize regenerating axonal structures in the dermis and epidermis, 50 um frozen sections were immunostained against axonal and Schwann cell markers. In all alloflaps, collateral axonal sprouts from adjacent recipient skin extended into the denervated skin component along the dermal-epidermal junction from the periphery towards the center. On day 100 post-transplant, regenerating sprouts reached 0.5 cm into the flap centripetally. Eight months following transplant, epidermal fibers were visualized 1.5 cm from the margin (rate of regeneration 0.06 mm per day. All animals had pinprick sensation in the periphery of the transplanted skin within 3 months post

  20. Nuclear expression of Snail1 in borderline and malignant epithelial ovarian tumours is associated with tumour progression

    International Nuclear Information System (INIS)

    Tuhkanen, Hanna; Soini, Ylermi; Kosma, Veli-Matti; Anttila, Maarit; Sironen, Reijo; Hämäläinen, Kirsi; Kukkonen, Laura; Virtanen, Ismo; Mannermaa, Arto

    2009-01-01

    Transcription factor Snail1 has a central role in induction of epithelial-mesenchymal transition (EMT). The aim of the present study was to elucidate the expression of Snail1 protein during epithelial ovarian tumourigenesis and to study the association of Snail1 expression with clinicopathological factors and prognosis. Epithelial and stromal fibroblast-like fusiform cells of 14 normal ovarian samples, 21 benign, 24 borderline and 74 malignant epithelial ovarian tumours were studied for Snail1 protein using immunohistochemistry. Nuclei of surface peritoneal cells of normal ovaries (n = 14) were regarded as negative for Snail1. Nuclear expression of Snail1 protein in epithelial ovarian tumours was increased during tumour progression from precursor lesions into carcinomas both in epithelial (p = 0.006) and stromal cells (p = 0.007). Nuclei of benign tumours (n = 21) were negative for Snail1. In borderline tumours (n = 24) occasional positive epithelial cells were found in 2 (8%) samples and in 3 (13%) samples stromal cells were focally positive for Snail1. In carcinomas (n = 74) focal Snail1 staining in epithelial cells was present in 17 (23%) tumours, and in stromal cells in 18 (24%) tumours. Nuclear expression of Snail1 in epithelial or stromal cells was not associated with clinicopathological factors or prognosis. Nuclear Snail1 expression seems to be related to tumour progression, and expression in borderline tumours indicates a role for Snail1 in early epithelial ovarian tumour development. Snail1 also appears to function more generally in tissue remodelling as positive staining was demonstrated in stromal cells

  1. Epithelial cell adhesion molecule - More than a carcinoma marker and adhesion molecule

    NARCIS (Netherlands)

    Trzpis, Monika; McLaughlin, Pamela M. J.; de Leij, Lou M. F. H.; Harmsen, Martin C.

    The epithetial cell adhesion molecule (EpCAM, CD326) is a glycoprotein of similar to 40 kd that was originally identified as a marker for carcinoma, attributable to its high expression on rapidly proliferating tumors of epithelial origin. Normal epithelia express EpCAM at a variable but generally

  2. Molecular mechanisms involved in casein gene expression and secretion in mouse mammary epithelial cells

    International Nuclear Information System (INIS)

    Lee, E.Y.H.P.; Lee, W.H.; Parry, G.; Bissell, M.J.

    1985-01-01

    Mouse mammary epithelial cells (MMEC) secrete a group of milk-specific proteins including various caseins and whey proteins. Dissociated mammary epithelial cells maintain expression of most of their differentiated functions only if cells are plated on a suitable substratum. Casein production and section, cell morphology, and production of α-lactalbumin have been used as markers to assess the degree of differentiation of mammary cells in culture. The general consensus is that cells express their differentiated properties at high levels and for longer periods of time on such substrata. In this paper, the authors demonstrate that modulation of the expression of caseins by floating collagen gels is manifested at several regulatory points

  3. Site-specific programming of the host epithelial transcriptome by the gut microbiota

    DEFF Research Database (Denmark)

    Sommer, Felix; Nookaew, Intawat; Sommer, Nina

    2015-01-01

    BACKGROUND: The intestinal epithelium separates us from the microbiota but also interacts with it and thus affects host immune status and physiology. Previous studies investigated microbiota-induced responses in the gut using intact tissues or unfractionated epithelial cells, thereby limiting....... The microbial impact on host gene expression was highly site specific, as epithelial responses to the microbiota differed between cell fractions. Specific transcriptional regulators were enriched in each fraction. In general, the gut microbiota induced a more rapid response in the colon than in the ileum...

  4. Human glomerular epithelial cell proteoglycans

    International Nuclear Information System (INIS)

    Thomas, G.J.; Jenner, L.; Mason, R.M.; Davies, M.

    1990-01-01

    Proteoglycans synthesized by cultures of human glomerular epithelial cells have been isolated and characterized. Three types of heparan sulfate were detected. Heparan sulfate proteoglycan I (HSPG-I; Kav 6B 0.04) was found in the cell layer and medium and accounted for 12% of the total proteoglycans synthesized. HSPG-II (Kav 6B 0.25) accounted for 18% of the proteoglycans and was located in the medium and cell layer. A third population (9% of the proteoglycan population), heparan sulfate glycosaminoglycan (HS-GAG; Kav 6B 0.4-0.8), had properties consistent with single glycosaminoglycan chains or their fragments and was found only in the cell layer. HSPG-I and HSPG-II from the cell layer had hydrophobic properties; they were released from the cell layer by mild trypsin treatment. HS-GAG lacked these properties, consisted of low-molecular-mass heparan sulfate oligosaccharides, and were intracellular. HSPG-I and -II released to the medium lacked hydrophobic properties. The cells also produced three distinct types of chondroitin sulfates. The major species, chondroitin sulfate proteoglycan I (CSPG-I) eluted in the excluded volume of a Sepharose CL-6B column, accounted for 30% of the proteoglycans detected, and was found in both the cell layer and medium. Cell layer CSPG-I bound to octyl-Sepharose. It was released from the cell layer by mild trypsin treatment. CSPG-II (Kav 6B 0.1-0.23) accounted for 10% of the total 35S-labeled macromolecules and was found predominantly in the culture medium. A small amount of CS-GAG (Kav 6B 0.25-0.6) is present in the cell extract and like HS-GAG is intracellular. Pulse-chase experiments indicated that HSPG-I and -II and CSPG-I and -II are lost from the cell layer either by direct release into the medium or by internalization where they are metabolized to single glycosaminoglycan chains and subsequently to inorganic sulfate

  5. Studying cytokinesis in Drosophila epithelial tissues.

    Science.gov (United States)

    Pinheiro, D; Bellaïche, Y

    2017-01-01

    Epithelial tissue cohesiveness is ensured through cell-cell junctions that maintain both adhesion and mechanical coupling between neighboring cells. During development, epithelial tissues undergo intensive cell proliferation. Cell division, and particularly cytokinesis, is coupled to the formation of new adhesive contacts, thereby preserving tissue integrity and propagating cell polarity. Remarkably, the geometry of the new interfaces is determined by the combined action of the dividing cell and its neighbors. To further understand the interplay between the dividing cell and its neighbors, as well as the role of cell division for tissue morphogenesis, it is important to analyze cytokinesis in vivo. Here we present methods to perform live imaging of cell division in Drosophila epithelial tissues and discuss some aspects of image processing and analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Peptidergic and non-peptidergic innervation and vasomotor responses of human lenticulostriate and posterior cerebral arteries

    DEFF Research Database (Denmark)

    Jansen-Olesen, Inger; Gulbenkian, Sergio; Engel, Ulla

    2004-01-01

    ) between the two vessels. However, the general pattern indicates stronger vasomotor responses (Emax and Imax) in the PCA branches as compared to the lenticulostriate arteries which may lend support for the clinical observation of a difference in stroke expression between the two vascular areas....

  7. Stimulation of Na+ -K+ -pump currents by epithelial nicotinic receptors in rat colon.

    Science.gov (United States)

    Bader, Sandra; Lottig, Lena; Diener, Martin

    2017-05-01

    Acetylcholine-induced epithelial Cl - secretion is generally thought to be mediated by epithelial muscarinic receptors and nicotinic receptors on secretomotor neurons. However, recent data have shown expression of nicotinic receptors by intestinal epithelium and the stimulation of Cl - secretion by nicotine, in the presence of the neurotoxin, tetrodotoxin. Here, we aimed to identify the transporters activated by epithelial nicotinic receptors and to clarify their role in cholinergic regulation of intestinal ion transport. Ussing chamber experiments were performed, using rat distal colon with intact epithelia. Epithelia were basolaterally depolarized to measure currents across the apical membrane. Apically permeabilized tissue was also used to measure currents across the basolateral membrane in the presence of tetrodotoxin. Nicotine had no effect on currents through Cl - channels in the apical membrane or on currents through K + channels in the apical or the basolateral membrane. Instead, nicotine stimulated the Na + -K + -pump as indicated by Na + -dependency and sensitivity of the nicotine-induced current across the basolateral membrane to cardiac steroids. Effects of nicotine were inhibited by nicotinic receptor antagonists such as hexamethonium and mimicked by dimethyl-4-phenylpiperazinium, a chemically different nicotinic agonist. Simultaneous stimulation of epithelial muscarinic and nicotinic receptors led to a strong potentiation of transepithelial Cl - secretion. These results suggest a novel concept for the cholinergic regulation of transepithelial ion transport by costimulation of muscarinic and nicotinic epithelial receptors and a unique role of nicotinic receptors controlling the activity of the Na + -K + -ATPase. © 2017 The British Pharmacological Society.

  8. Surgical management of anterior chamber epithelial cysts.

    Science.gov (United States)

    Haller, Julia A; Stark, Walter J; Azab, Amr; Thomsen, Robert W; Gottsch, John D

    2003-03-01

    To review management strategies for treatment of anterior chamber epithelial cysts. Retrospective review of consecutive interventional case series. Charts of patients treated for epithelial ingrowth over a 10-year period by a single surgeon were reviewed. Cases of anterior chamber epithelial cysts were identified and recorded, including details of ocular history, preoperative and postoperative acuity, intraocular pressure (IOP), and ocular examination, type of surgical intervention, and details of further procedures performed. Seven eyes with epithelial cysts were identified. Patient age ranged from 1.5 to 53 years at presentation. Four patients were children. In four eyes, cysts were secondary to trauma, one case was presumably congenital, one case developed after corneal perforation in an eye with Terrien's marginal degeneration, and one case developed after penetrating keratoplasty (PK). Three eyes were treated with vitrectomy, en bloc resection of the cyst and associated tissue, fluid-air exchange and cryotherapy. The last four eyes were treated with a new conservative strategy of cyst aspiration (three cases) or local excision (one keratin "pearl" cyst), and endolaser photocoagulation of the collapsed cyst wall/base. All epithelial tissue was successfully eradicated by clinical criteria; one case required repeat excision (follow-up, 9 to 78 months, mean 45). Two eyes required later surgery for elevated IOP, two for cataract extraction and one for repeat PK. Final visual acuity ranged from 20/20 to hand motions, depending on associated ocular damage. Best-corrected visual results were obtained in the more conservatively managed eyes. Anterior chamber epithelial cysts can be managed conservatively in selected cases with good results. This strategy may be particularly useful in children's eyes, where preservation of the lens, iris, and other structures may facilitate amblyopia management. Copyright 2003 by Elsevier Science Inc.

  9. Phototherapeutic LASEK for a persistent epithelial defect and a recurrent epithelial erosion.

    Science.gov (United States)

    Hondur, Ahmet; Bilgihan, Kamil; Hasanreisoglu, Berati

    2005-01-01

    To present two patients, one with persistent epithelial defect and one with recurrent epithelial erosion, unresponsive to conventional therapy treated with phototherapeutic keratectomy (PTK) with the laser subepithelial keratomileusis (LASEK) technique (phototherapeutic LASEK). The epithelial flap was created following 18% ethanol application for 20 seconds. A 10-microm deep ablation was performed in the central 7.0-mm zone. A contact lens was placed and the patient examined daily until epithelial closure. Upon epithelial closure, the contact lens was removed. A mild topical steroid and artificial tears were applied for 2 weeks. The epithelium healed in 4 days in both patients. Patients reported only mild pain until epithelial closure. The manifest refraction and uncorrected visual acuity remained unchanged in both eyes. No haze was noted. The first patient has remained asymptomatic without any recurrence for 12 months, and the second for 9 months. Phototherapeutic LASEK provides a therapeutic option for refractory recurrent erosions and persistent epithelial defects, with the additional benefit of being less painful and less risky for haze development than conventional PTK.

  10. Extensive Focal Epithelial Hyperplasia: A Case Report.

    Science.gov (United States)

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck's disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis.

  11. Management of herpes simplex virus epithelial keratitis.

    Science.gov (United States)

    Roozbahani, Mehdi; Hammersmith, Kristin M

    2018-04-24

    To review recent advancements in the management of herpes simplex virus (HSV) epithelial keratitis. Trifluridine eye drop, acyclovir (ACV) ointment, ganciclovir gel, and oral ACV are still the main therapeutic agents. Cryopreserved amniotic membrane has been recently used as an adjuvant treatment. Resistance to ACV has become a concerning issue. The animal models of HSV vaccine are able to reduce HSV keratitis. New antivirals are under development. Current cases of HSV epithelial keratitis are manageable with available medications, but new advancements are required to decrease disease burden in the future. HSV vaccine can be revolutionary.

  12. Segmentation and Quantitative Analysis of Epithelial Tissues.

    Science.gov (United States)

    Aigouy, Benoit; Umetsu, Daiki; Eaton, Suzanne

    2016-01-01

    Epithelia are tissues that regulate exchanges with the environment. They are very dynamic and can acquire virtually any shape; at the cellular level, they are composed of cells tightly connected by junctions. Most often epithelia are amenable to live imaging; however, the large number of cells composing an epithelium and the absence of informatics tools dedicated to epithelial analysis largely prevented tissue scale studies. Here we present Tissue Analyzer, a free tool that can be used to segment and analyze epithelial cells and monitor tissue dynamics.

  13. Generalized Superconductivity. Generalized Levitation

    International Nuclear Information System (INIS)

    Ciobanu, B.; Agop, M.

    2004-01-01

    In the recent papers, the gravitational superconductivity is described. We introduce the concept of generalized superconductivity observing that any nongeodesic motion and, in particular, the motion in an electromagnetic field, can be transformed in a geodesic motion by a suitable choice of the connection. In the present paper, the gravitoelectromagnetic London equations have been obtained from the generalized Helmholtz vortex theorem using the generalized local equivalence principle. In this context, the gravitoelectromagnetic Meissner effect and, implicitly, the gravitoelectromagnetic levitation are given. (authors)

  14. Selective plasticity of primary afferent innervation to the dorsal horn and autonomic nuclei following lumbosacral ventral root avulsion and reimplantation in long term studies.

    Science.gov (United States)

    Wu, Lisa; Wu, Jun; Chang, Huiyi H; Havton, Leif A

    2012-02-01

    Previous studies involving injuries to the nerves of the cauda equina and the conus medullaris have shown that lumbosacral ventral root avulsion in rat models results in denervation and dysfunction of the lower urinary tract, retrograde and progressive cell death of the axotomized motor and parasympathetic neurons, as well as the emergence of neuropathic pain. Root reimplantation has also been shown to ameliorate several of these responses, but experiments thus far have been limited to studying the effects of lesion and reimplantation local to the lumbosacral region. Here, we have expanded the region of investigation after lumbosacral ventral root avulsion and reimplantation to include the thoracolumbar sympathetic region of the spinal cord. Using a retrograde tracer injected into the major pelvic ganglion, we were able to define the levels of the spinal cord that contain sympathetic preganglionic neurons innervating the lower urinary tract. We have conducted studies on the effects of the lumbosacral ventral root avulsion and reimplantation models on the afferent innervation of the dorsal horn and autonomic nuclei at both thoracolumbar and lumbosacral levels through immunohistochemistry for the markers calcitonin gene-related peptide (CGRP) and vesicular glutamate transporter 1 (VGLUT1). Surprisingly, our experiments reveal a selective and significant decrease of CGRP-positive innervation in the dorsal horn at thoracolumbar levels that is partially restored with root reimplantation. However, no similar changes were detected at the lumbosacral levels despite the injury and repair targeting efferent neurons, and being performed at the lumbosacral levels. Despite the changes evident in the thoracolumbar dorsal horn, we find no changes in afferent innervation of the autonomic nuclei at either sympathetic or parasympathetic segmental levels by CGRP or VGLUT1. We conclude that even remote, efferent root injuries and repair procedures can have an effect on remote and non

  15. Spatiotemporal dynamics of re-innervation and hyperinnervation patterns by uninjured CGRP fibers in the rat foot sole epidermis after nerve injury

    Directory of Open Access Journals (Sweden)

    Duraku Liron S

    2012-08-01

    Full Text Available Abstract The epidermis is innervated by fine nerve endings that are important in mediating nociceptive stimuli. However, their precise role in neuropathic pain is still controversial. Here, we have studied the role of epidermal peptidergic nociceptive fibers that are located adjacent to injured fibers in a rat model of neuropathic pain. Using the Spared Nerve Injury (SNI model, which involves complete transections of the tibial and common peroneal nerve while sparing the sural and saphenous branches, mechanical hypersensitivity was induced of the uninjured lateral (sural and medial (saphenous area of the foot sole. At different time points, a complete foot sole biopsy was taken from the injured paw and processed for Calcitonin Gene-Related Peptide (CGRP immunohistochemistry. Subsequently, a novel 2D-reconstruction model depicting the density of CGRP fibers was made to evaluate the course of denervation and re-innervation by uninjured CGRP fibers. The results show an increased density of uninjured CGRP-IR epidermal fibers on the lateral and medial side after a SNI procedure at 5 and 10 weeks. Furthermore, although in control animals the density of epidermal CGRP-IR fibers in the footpads was lower compared to the surrounding skin of the foot, 10 weeks after the SNI procedure, the initially denervated footpads displayed a hyper-innervation. These data support the idea that uninjured fibers may play a considerable role in development and maintenance of neuropathic pain and that it is important to take larger biopsies to test the relationship between innervation of injured and uninjured nerve areas.

  16. Coronavirus infection of polarized epithelial cells

    NARCIS (Netherlands)

    Rossen, J W; Horzinek, M C; Rottier, P J

    1995-01-01

    Epithelial cells are the first host cells to be infected by incoming c oronaviruses. Recent observations in vitro show that coronaviruses are released from a specific side of these polarized cells, and this polarized release might be important for the spread of the infection in vivo. Mechanisms for

  17. THE BUFFER CAPACITY OF AIRWAY EPITHELIAL SECRETIONS

    Directory of Open Access Journals (Sweden)

    Dusik eKim

    2014-06-01

    Full Text Available The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF. The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 µl volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO3- is the major buffer. Peak buffer capacity (β increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO3- secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO3- secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions.

  18. Do topical antibiotics help corneal epithelial trauma?

    OpenAIRE

    King, J. W.; Brison, R. J.

    1993-01-01

    Topical antibiotics are routinely used in emergency rooms to treat corneal trauma, although no published evidence supports this treatment. In a noncomparative clinical trial, 351 patients with corneal epithelial injuries were treated without antibiotics. The infection rate was 0.7%, suggesting that such injuries can be safely and effectively managed without antibiotics. A comparative clinical trial is neither warranted nor feasible.

  19. Cytokine Tuning of Intestinal Epithelial Function

    Directory of Open Access Journals (Sweden)

    Caroline Andrews

    2018-06-01

    Full Text Available The intestine serves as both our largest single barrier to the external environment and the host of more immune cells than any other location in our bodies. Separating these potential combatants is a single layer of dynamic epithelium composed of heterogeneous epithelial subtypes, each uniquely adapted to carry out a subset of the intestine’s diverse functions. In addition to its obvious role in digestion, the intestinal epithelium is responsible for a wide array of critical tasks, including maintaining barrier integrity, preventing invasion by microbial commensals and pathogens, and modulating the intestinal immune system. Communication between these epithelial cells and resident immune cells is crucial for maintaining homeostasis and coordinating appropriate responses to disease and can occur through cell-to-cell contact or by the release or recognition of soluble mediators. The objective of this review is to highlight recent literature illuminating how cytokines and chemokines, both those made by and acting on the intestinal epithelium, orchestrate many of the diverse functions of the intestinal epithelium and its interactions with immune cells in health and disease. Areas of focus include cytokine control of intestinal epithelial proliferation, cell death, and barrier permeability. In addition, the modulation of epithelial-derived cytokines and chemokines by factors such as interactions with stromal and immune cells, pathogen and commensal exposure, and diet will be discussed.

  20. Heterogeneity of limbal basal epithelial progenitor cells.

    Science.gov (United States)

    Hayashida, Yasutaka; Li, Wei; Chen, Ying-Ting; He, Hua; Chen, Szu-yu; Kheirkah, Ahmad; Zhu, Ying-Tien; Matsumoto, Yukihiro; Tseng, Scheffer C G

    2010-11-01

    Although corneal epithelial stem cells (SCs) are located at the limbus between the cornea and the conjunctiva, not all limbal basal epithelial cells are SCs. Using 2 dispase digestions to remove different amounts of limbal basal epithelial cells for cross-sections, flat mounts, and cytospin preparations, double immunostaining to pancytokeratins (PCK) and vimentin (Vim) identified 3 p63+ epithelial progenitors such as PCK-/Vim+, PCK/Vim, and PCK-/Vim+ and 1 p63+ mesenchymal cell, PCK-/Vim+. PCK-/Vim- progenitors had the smallest cell size were 10-20 times more enriched on collagen I-coated dishes in the 5-minute rapid adherent fraction that contained the highest percentage of p63+ cells but the lowest percentage of cytokeratin12+ cells, and gave rise to high Ki67 labeling and vivid clonal growth. In contrast, PCK+/Vim+ and PCK+/Vim- progenitors were found more in the slow-adherent fraction and yielded poor clonal growth. PCK/Vim progenitors and clusters of PCK-/Vim+ mesenchymal cells, which were neither melanocytes nor Langerhans cells, were located in the limbal basal region. Therefore, differential expression of PCK and Vim helps identify small PCK-/Vim- cells as the most likely candidate for SCs among a hierarchy of heterogeneous limbal basal progenitors, and their close association with PCK-/Vim+ presumed "niche" cells.

  1. Interaction with Epithelial Cells Modifies Airway Macrophage Response to Ozone

    Science.gov (United States)

    The initial innate immune response to ozone (03) in the lung is orchestrated by structural cells, such as epithelial cells, and resident immune cells, such as airway macrophages (Macs). We developed an epithelial cell-Mac coculture model to investigate how epithelial cell-derived...

  2. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  3. The influence of electromyographic recording methods and the innervation zone on the mean power frequency-torque relationships.

    Science.gov (United States)

    Herda, Trent J; Zuniga, Jorge M; Ryan, Eric D; Camic, Clayton L; Bergstrom, Haley C; Smith, Doug B; Weir, Joseph P; Cramer, Joel T; Housh, Terry J

    2015-06-01

    This study examined the effects of electromyographic (EMG) recording methods and innervation zone (IZ) on the mean power frequency (MPF)-torque relationships. Nine subjects performed isometric ramp muscle actions of the leg extensors from 5% to 100% of maximal voluntary contraction with an eight channel linear electrode array over the IZ of the vastus lateralis. The slopes were calculated from the log-transformed monopolar and bipolar EMG MPF-torque relationships for each channel and subject and 95% confidence intervals (CI) were constructed around the slopes for each relationship and the composite of the slopes. Twenty-two to 55% of the subjects exhibited 95% CIs that did not include a slope of zero for the monopolar EMG MPF-torque relationships while 25-75% of the subjects exhibited 95% CIs that did not include a slope of zero for the bipolar EMG MPF-torque relationships. The composite of the slopes from the EMG MPF-torque relationships were not significantly different from zero for any method or channel, however, the method and IZ location slightly influenced the number of significant slopes on a subject-by-subject basis. The log-transform model indicated that EMG MPF-torque patterns were nonlinear regardless of recording method or distance from the IZ. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Effects of the innervation zone on the time and frequency domain parameters of the surface electromyographic signal.

    Science.gov (United States)

    Smith, Cory M; Housh, Terry J; Herda, Trent J; Zuniga, Jorge M; Ryan, Eric D; Camic, Clayton L; Bergstrom, Haley C; Smith, Doug B; Weir, Joseph P; Cramer, Joel T; Hill, Ethan C; Cochrane, Kristen C; Jenkins, Nathaniel D M; Schmidt, Richard J; Johnson, Glen O

    2015-08-01

    The purposes of the present study were to examine the effects of electrode placements over, proximal, and distal to the innervation zone (IZ) on electromyographic (EMG) amplitude (RMS) and frequency (MPF) responses during: (1) a maximal voluntary isometric contraction (MVIC), and; (2) a sustained, submaximal isometric muscle action. A linear array was used to record EMG signals from the vastus lateralis over the IZ, 30mm proximal, and 30mm distal to the IZ during an MVIC and a sustained isometric muscle action of the leg extensors at 50% MVIC. During the MVIC, lower EMG RMS (p>0.05) and greater EMG MPF (ptime relationships over, proximal, and distal to the IZ occurred. Thus, the results of the present study indicated that during an MVIC, EMG RMS and MPF values recorded over the IZ are not comparable to those away from the IZ. However, the rates of fatigue-induced changes in EMG RMS and MPF during sustained, submaximal isometric muscle actions of the leg extensors were the same regardless of the electrode placement locations relative to the IZ. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Quantifying the effects of electrode distance from the innervation zone on the electromyographic amplitude versus torque relationships

    International Nuclear Information System (INIS)

    Herda, Trent J; Weir, Joseph P; Zuniga, Jorge M; Ryan, Eric D; Camic, Clayton L.; Bergstrom, Haley C; Cramer, Joel T; Housh, Terry J; Smith, Doug B

    2013-01-01

    The present study applied a log-transformation model to compare the electromyographic (EMG) amplitude versus torque relationships from monopolar EMG signals up to 35 mm proximal and distal from the innervation zone (IZ). Seven men (age = 23 ± 2 year; mass = 82 ± 10 kg) and two women (age = 21 ± 1 year; mass = 62 ± 8 kg) performed isometric ramp contractions of the right leg extensors with an eight-channel linear electrode array positioned over the vastus lateralis with the IZ located between channels 4 and 5. Linear regression models were fit to the log-transformed monopolar EMG RMS –torque relationships with the b terms (slope) and the a terms (Y-intercept) calculated for each channel and subject. The b terms for channels 4, 5, and 6 were higher (P ≤ 0.05) than the more distal channels 7 and 8 (P < 0.05). In contrast, there were no differences (P > 0.05) among the a terms of the eight channels. Thus, the shapes of the monopolar EMG RMS –torque relationships were altered as a function of distance between the IZ and recording area, which may be helpful for clinicians and researchers who infer changes in motor control strategies based on the shapes of the EMG RMS –torque relationships. (paper)

  6. Scintigraphic assessment of cardiac sympathetic innervation with I-123-metaiodobenzylguanidine in cardiomyopathy. Special reference to cardiac arrhythmia

    Energy Technology Data Exchange (ETDEWEB)

    Asano, Takahisa; Otsuka, Nobuaki; Sone, Teruki; Mimura, Hiroaki; Yanagimoto, Shinichi; Tomomitsu, Tatsushi; Fukunaga, Masao [Kawasaki Medical School, Kurashiki, Okayama (Japan); Morita, Koichi

    1999-07-01

    Cardiac sympathetic imagings with I-123-metaiodobenzylguanidine (MIBG) were carried out in 5 cases with dilated cardiomyopathy (DCM), 26 cases with hypertrophic cardiomyopathy (HCM), and 4 cases without cardiac disease as a control to assess cardiac sympathetic innervation qualitatively and quantitatively, and to clarify the relation of MIBG accumulation to arrhythmia. MIBG scintigraphy was performed at 15 min. (early image) and 4 hr. (delayed image) after intravenous injection of MIBG 111 MBq. The MIBG uptake ratio of mediastinum (H/M) and the cardiac washout rate (WR) from early to delayed images were calculated. On both early and delayed SPECTs, MIBG uptake was assessed by defect scores (DSs). Regarding the cases with HCM, the MIBG uptake ratio, WR, and DS were also compared in cases with and without arrhythmia. In DCM, the MIBG uptake on delayed SPECT was markedly low, the H/M ratio was significantly lower, and the DS was significantly higher than in the control (all p<0.05). As for the WR, there was no significant difference between HCM, DCM and the control. In HCM, significantly reduced MIBG uptake was observed in cases with ventricular techycardia (VT) and in cases with atrial fibrillation (Af), as compared with cases without arrhythmia (all p<0.05). There results suggest that MIBG scintigraphy might be a useful tool in the assessment of cardiac sympathetic abnormalities in cardiomyopathy, especially in cases with arrhythmia. (author)

  7. FMRFamide-like immunoreactive neurons of the nervus terminalis of teleosts innervate both retina and pineal organ.

    Science.gov (United States)

    Ekström, P; Honkanen, T; Ebbesson, S O

    1988-09-13

    The tetrapeptide FMRFamide (Phe-Met-Arg-Phe-NH2) was first isolated from molluscan ganglia. Subsequently, it has become clear that vertebrate brains also contain endogenous FMRFamide-like substances. In teleosts, the neurons of the nervus terminalis contain an FMRFamide-like substance, and provide a direct innervation to the retina (Proc. Natl. Acad. Sci. U.S.A., 81 [1984] 940-944). Here we report the presence of FMRFamide-immunoreactive axonal bundles in the pineal organ of Coho salmon and three-spined sticklebacks. The largest numbers of axons were observed proximal to the brain, in the pineal stalk, while the distal part of the pineal organ contained only few axons. No FMRFamide-like-immunoreactive (IR) cell bodies were observed in the pineal organ. In adult fish it was not possible to determine the origin of these axons, due to the large numbers of FMRFamide-like IR axons in the teleost brain. However, by following the development of FMRFamide-like IR neurons in the embryonic and larval stickleback brain, it was possible to conclude that, at least in newly hatched fish, FMRFamide-like IR axons that originate in the nucleus nervus terminalis reach the pineal organ. Thus, it seems there is a direct connection between a specialized part of the chemosensory system and both the retina and the pineal organ in teleost fish.

  8. Tissue engineering the mechanosensory circuit of the stretch reflex arc: sensory neuron innervation of intrafusal muscle fibers.

    Science.gov (United States)

    Rumsey, John W; Das, Mainak; Bhalkikar, Abhijeet; Stancescu, Maria; Hickman, James J

    2010-11-01

    The sensory circuit of the stretch reflex arc, composed of specialized intrafusal muscle fibers and type Ia proprioceptive sensory neurons, converts mechanical information regarding muscle length and stretch to electrical action potentials and relays them to the central nervous system. Utilizing a non-biological substrate, surface patterning photolithography and a serum-free medium formulation a co-culture system was developed that facilitated functional interactions between intrafusal muscle fibers and sensory neurons. The presence of annulospiral wrappings (ASWs) and flower-spray endings (FSEs), both physiologically relevant morphologies in sensory neuron-intrafusal fiber interactions, were demonstrated and quantified using immunocytochemistry. Furthermore, two proposed components of the mammalian mechanosensory transduction system, BNaC1 and PICK1, were both identified at the ASWs and FSEs. To verify functionality of the mechanoreceptor elements the system was integrated with a MEMS cantilever device, and Ca(2+) currents were imaged along the length of an axon innervating an intrafusal fiber when stretched by cantilever deflection. This system provides a platform for examining the role of this mechanosensory complex in the pathology of myotonic and muscular dystrophies, peripheral neuropathy, and spasticity inducing diseases like Parkinson's. These studies will also assist in engineering fine motor control for prosthetic devices by improving our understanding of mechanosensitive feedback. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  9. ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation.

    Science.gov (United States)

    Seijffers, Rhona; Zhang, Jiangwen; Matthews, Jonathan C; Chen, Adam; Tamrazian, Eric; Babaniyi, Olusegun; Selig, Martin; Hynynen, Meri; Woolf, Clifford J; Brown, Robert H

    2014-01-28

    ALS is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons and atrophy of distal axon terminals in muscle, resulting in loss of motor function. Motor end plates denervated by axonal retraction of dying motor neurons are partially reinnervated by remaining viable motor neurons; however, this axonal sprouting is insufficient to compensate for motor neuron loss. Activating transcription factor 3 (ATF3) promotes neuronal survival and axonal growth. Here, we reveal that forced expression of ATF3 in motor neurons of transgenic SOD1(G93A) ALS mice delays neuromuscular junction denervation by inducing axonal sprouting and enhancing motor neuron viability. Maintenance of neuromuscular junction innervation during the course of the disease in ATF3/SOD1(G93A) mice is associated with a substantial delay in muscle atrophy and improved motor performance. Although disease onset and mortality are delayed, disease duration is not affected. This study shows that adaptive axonal growth-promoting mechanisms can substantially improve motor function in ALS and importantly, that augmenting viability of the motor neuron soma and maintaining functional neuromuscular junction connections are both essential elements in therapy for motor neuron disease in the SOD1(G93A) mice. Accordingly, effective protection of optimal motor neuron function requires restitution of multiple dysregulated cellular pathways.

  10. Estrogen replacement avoids the decrease of bladder innervations in ovariectomized adult virgin rats: in vivo stereological study.

    Science.gov (United States)

    de Fraga, Rogerio; Palma, Paulo; Dambros, Miriam; Riccetto, Cassio L Z; Mandarim-de-Lacerda, Carlos; Miyaoka, Ricardo

    2009-05-01

    The authors quantified the nerve fibers in the bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old). Group 1: remained intact; Group 2: underwent bilateral ovariectomy, and after 30 days was started on subcutaneous sesame oil replacement (0.2 ml per day) for 90 days; Group 3: sham-operated, and after 30 days was started on subcutaneous sesame oil replacement (0.2 ml per day) for 90 days; Group 4: bilateral ovariectomy, and after 30 days was started on subcutaneous injection of 17β-estradiol (10 μg/kg body weight) for 90 days. S-100 was used to stain nerves myelinized fibers on paraffin rat bladder sections. The G-50 grid system was used to quantitatively analyze the fibers. Long-term estrogen deprivation caused significant changes in bladder innervations, which can be characterized by a decreased number of nerve fibers by 65% (p < 0.001).

  11. Immmunohistochemical study of the blood and lymphatic vasculature and the innervation of mouse gut and gut-associated lymphoid tissue.

    Science.gov (United States)

    Ma, B; von Wasielewski, R; Lindenmaier, W; Dittmar, K E J

    2007-02-01

    The blood and lymphatic vascular system of the gut plays an important role in tissue fluid homeostasis, nutrient absorption and immune surveillance. To obtain a better understanding of the anatomic basis of these functions, the blood and lymphatic vasculature of the lower segment of mouse gut and several constituents of gut-associated lymphoid tissue (GALT) including Peyer's patch, specialized lymphoid nodules in the caecum, small lymphoid aggregates and lymphoid nodules in the colon were studied by using confocal microscopy. Additionally, the innervation and nerve/immune cell interactions in the gut and Peyer's patch were investigated by using cell surface marker PGP9.5 and Glial fibrillary acidic protein (GFAP). In the gut and Peyer's patch, the nerves have contact with B cell, T cell and B220CD3 double-positive cells. Dendritic cells, the most important antigen-presenting cells, were closely apposed to some nerves. Some dendritic cells formed membrane-membrane contact with nerve terminals and neuron cell body. Many fine nerve fibres, which are indirectly detected by GFAP, have contact with dendritic cells and other immune cells in the Peyer's patch. Furthermore, the expression of Muscarinic Acetylcholine receptor (subtype M2) was characterized on dendritic cells and other cell population. These findings are expected to provide a route to understand the anatomic basis of neuron-immune regulation/cross-talk and probably neuroinvasion of prion pathogens in the gut and GALT.

  12. Prenatal cocaine increases striatal serotonin innervation without altering the patch/matrix organization of intrinsic cell types.

    Science.gov (United States)

    Snyder-Keller, A M; Keller, R W

    1993-08-20

    The effect of prenatal cocaine on the anatomical development of the striatum was examined. The distribution and density of dopaminergic innervation of the striatum of animals exposed to cocaine during the second and third week of gestation was not noticeably different from prenatally saline-injected or untreated controls at any age. The patch/matrix organization of the striatum also appeared unaltered: neurons exhibiting dense substance P staining were localized to patches that overlapped dopamine terminal patches early in development, and enkephalin- and calbindin-immunoreactive neurons were found segregated to the matrix. Histochemical staining for acetylcholinesterase and NADPH diaphorase also revealed no differences between prenatally cocaine-treated and control brains. Whereas prenatal cocaine treatment failed to modify the basic compartmental organization of the striatum, it did lead to a hyperinnervation of serotonin-immunoreactive fibers which developed slowly after birth. Thus prenatal exposure to cocaine is capable of altering the ingrowth of serotonergic projections to the striatum while producing no change in the organization of neurons intrinsic to the striatum.

  13. Unilateral sectioning of the superior ovarian nerve of rats with polycystic ovarian syndrome restores ovulation in the innervated ovary

    Directory of Open Access Journals (Sweden)

    Morales-Ledesma Leticia

    2010-08-01

    Full Text Available Abstract The present study tested the hypothesis that if polycystic ovary syndrome (PCOS results from activating the noradrenergic outflow to the ovary, unilaterally sectioning the superior ovarian nerve (SON will result in ovulation by the denervated ovary, and the restoration of progesterone (P4, testosterone (T and estradiol (E2 normal serum level. A single 2 mg dose of estradiol valerate (EV to adult rats results in the development of a syndrome similar to the human PCOS. Ten-day old rats were injected with EV or vehicle solution (Vh and were submitted to sham surgery, unilateral or bilateral sectioning of the SON at 24-days of age. The animals were sacrificed at 90 to 92 days of age, when they presented vaginal estrus preceded by a pro-estrus smear. In EV-treated animals, unilateral sectioning of the SON restored ovulation by the innervated ovary and unilateral or bilateral sectioning of the SON normalized testosterone and estradiol levels. These results suggest that aside from an increase in ovarian noradrenergic tone in the ovaries, in the pathogenesis of the PCOS participate other neural influences arriving to the ovaries via the SON, regulating spontaneous ovulation. Changes in P4, T and E2 serum levels induced by EV treatment seem to be controlled by neural signals arising from the abdominal wall and other signals arriving to the ovaries through the SON, and presents asymmetry.

  14. Neo-phalloplasty with re-innervated latissimus dorsi free flap: a functional study of a novel technique.

    Science.gov (United States)

    Ranno, R; Veselý, J; Hýza, P; Stupka, I; Justan, I; Dvorák, Z; Monni, N; Novák, P; Ranno, S

    2007-01-01

    Twenty two patients with gender dysphoria underwent neo-phalloplasties using a novel technique. Latissimus dorsi musculocutaneus re-innervated free flap was used to allow voluntary rigidity of the neo-penis. From the first 22 patients, 18 have obtained motoric function of reconstructed penis; the "paradox erection" was obtained. 14 patients came for examination after a follow-up period of mean 26.4 months. We evaluated the motility and shape changes of neo-phallus measuring its different size and dimension during relax and muscle contraction. The range of neo-phallus length in relaxed position was between 7 and 17 cm (mean 12.2 cm), its circumference in the same position had a range between 13 and 20 cm (mean 13.7 cm). All patients were able to contract the muscle with an average length reduction of 3.08 cm and an average circumference enlargement of 4 cm. In this study, the dimensions and motility were quantified demonstrating the neo-phallus function and size changes during sexual intercourse.

  15. Protective effects of trehalose on the corneal epithelial cells.

    Science.gov (United States)

    Aragona, Pasquale; Colosi, Pietro; Rania, Laura; Colosi, Francesca; Pisani, Antonina; Puzzolo, Domenico; Micali, Antonio

    2014-01-01

    Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination. Twelve patients undergoing laser subepithelial keratomileusis (LASEK) were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups. In both trehalose-untreated eyes (TUE) and trehalose-treated eyes (TTE), the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups. Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls.

  16. Protective Effects of Trehalose on the Corneal Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Pasquale Aragona

    2014-01-01

    Full Text Available Purpose. Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination. Methods. Twelve patients undergoing laser subepithelial keratomileusis (LASEK were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups. Results. In both trehalose-untreated eyes (TUE and trehalose-treated eyes (TTE, the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups. Conclusions. Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls.

  17. Epithelial to Mesenchymal Transition in a Clinical Perspective

    Directory of Open Access Journals (Sweden)

    Jennifer Pasquier

    2015-01-01

    Full Text Available Tumor growth and metastatic dissemination rely on cellular plasticity. Among the different phenotypes acquired by cancer cells, epithelial to mesenchymal transition (EMT has been extensively illustrated. Indeed, this transition allows an epithelial polarized cell to acquire a more mesenchymal phenotype with increased mobility and invasiveness. The role of EMT is quite clear during developmental stage. In the neoplastic context in many tumors EMT has been associated with a more aggressive tumor phenotype including local invasion and distant metastasis. EMT allows the cell to invade surrounding tissues and survive in the general circulation and through a stem cell phenotype grown in the host organ. The molecular pathways underlying EMT have also been clearly defined and their description is beyond the scope of this review. Here we will summarize and analyze the attempts made to block EMT in the therapeutic context. Indeed, till today, most of the studies are made in animal models. Few clinical trials are ongoing with no obvious benefits of EMT inhibitors yet. We point out the limitations of EMT targeting such tumor heterogeneity or the dynamics of EMT during disease progression.

  18. Involuntary movement during mastication in patients with long-term facial paralysis reanimated with a partial gracilis free neuromuscular flap innervated by the masseteric nerve.

    Science.gov (United States)

    Rozen, Shai; Harrison, Bridget

    2013-07-01

    Midface reanimation in patients with chronic facial paralysis is not always possible with an ipsilateral or contralateral facial nerve innervating a free neuromuscular tissue transfer. Alternate use of nonfacial nerves is occasionally indicated but may potentially result in inadvertent motions. The goal of this study was to objectively review videos of patients who underwent one-stage reanimation with a gracilis muscle transfer innervated by the masseteric nerve for (1) inadvertent motion during eating, (2) characterization of masticatory patterns, and (3) social hindrance perceived by the patients during meals. Between the years 2009 and 2012, 18 patients underwent midfacial reanimation with partial gracilis muscle transfer coapted to the masseter nerve for treatment of midfacial paralysis. Sixteen patients were videotaped in detail while eating. Involuntary midface movement on the reconstructed side and mastication patterns were assessed. In addition, 16 patients were surveyed as to whether involuntary motion constituted a problem in their daily lives. All 16 patients videotaped during mastication demonstrated involuntary motion on the reconstructed side while eating. Several unique masticatory patterns were noted as well. Only one of the 16 patients reported involuntary motion as a minor disturbance in daily life during meals. All patients with chronic facial paralysis who plan to undergo midface reanimation with a free tissue transfer innervated by the ipsilateral masseter nerve should be told that they would universally have involuntary animation during mastication. Most patients do not consider this a major drawback in their daily lives. Therapeutic, IV.

  19. Fundamental study on nuclear medicine imaging of cholinergic innervation in the brain; Changes of neurotransmitter and receptor in animal model of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, Hiroshi; Kinuya, Keiko; Sumiya, Hisashi; Hisada, Kinichi [Kanazawa Univ. (Japan). School of Medicine; Tsuji, Shiro; Terada, Hitoshi; Shiba, Kazuhiro; Mori, Hirofumi

    1990-10-01

    A fundamental study was performed on the nuclear medicine imaging of cholinergic innervation in the brain. In a cholinergic denervation model prepared by producing an unilateral basal forebrain lesion in the rat, which is reported to be one of animal models of Alzheimer' disease, quantitative determination of acetylcholine in parietal cortices revealed statistically significant 31% decrease on an average in the ipsilateral side relative to the contralateral side to the lesion. In vitro receptor autoradiography showed no significant differences in total, M{sub 1}, and M{sub 2} muscarinic acetylcholine receptors between the ipsilateral and contralateral cortices to the lesion. Simultaneous mapping of presynaptic cholinergic innervation using {sup 3}H-2-(4-phenylpiperidino) cyclohexanol (AH5183) demonstrated significant 14% decrease of AH5183 binding on an average in the ipsilateral relative to the contralateral fronto-parieto-temporal cortices to the lesion. These results suggest that AH5183 is a promising ligand for mapping cholinergic innervation in nuclear medicine imaging. (author).

  20. Abnormal sympathetic innervation of the heart in a patient with Emery-Dreifuss muscular dystrophy.

    Science.gov (United States)

    Fujiita, Takashi; Shimizu, Masami; Kaku, Bunji; Kanaya, Hounin; Horita, Yuki; Uno, Yoshihide; Yamazaki, Tsukasa; Ohka, Takio; Sakata, Kenji; Mabuchi, Hiroshi

    2005-07-01

    A 33-year-old man was admitted for general malaise and vomiting. An electrocardiogram showed a complete atrioventricular block and an echocardiogram showed right atrial dilatation and normal wall motion of left ventricle (LV). Gene analysis showed nonsense mutation in the STA gene, which codes for emerin, and Emery-Dreifuss muscular dystrophy was diagnosed. An endomyocardial biopsy of right ventricle showed mild hypertrophy of myocytes. Myocardial scintigraphic studies with Tc-99m methoxyisobutylisonitrile (MIBI) and I-123-betamethyl-p-iodophenylpentadecanoic acid (BMIPP) scintigrams showed no abnormalities. In contrast, I-123 metaiodobenzylguanidine (MIBG) scintigrams showed a diffuse and severe decrease in accumulation of MIBG in the heart. Six months later, his LV wall motion on echocardiograms developed diffuse hypokinesis. These results suggest that the abnormality on I-123 MIBG myocardial scintigrams may predict LV dysfunction in Emery-Dreifuss muscular dystrophy.

  1. General general game AI

    OpenAIRE

    Togelius, Julian; Yannakakis, Georgios N.; 2016 IEEE Conference on Computational Intelligence and Games (CIG)

    2016-01-01

    Arguably the grand goal of artificial intelligence research is to produce machines with general intelligence: the capacity to solve multiple problems, not just one. Artificial intelligence (AI) has investigated the general intelligence capacity of machines within the domain of games more than any other domain given the ideal properties of games for that purpose: controlled yet interesting and computationally hard problems. This line of research, however, has so far focuse...

  2. Epithelial cell proliferation in human fundic and antral mucosae. Influence of superselective vagotomy and relationship with gastritis

    International Nuclear Information System (INIS)

    Gutierrez, O.; Lehy, T.; Rene, E.; Gres, L.; Bonfils, S.

    1985-01-01

    Epithelial cell proliferation in the fundic and antral mucosae was studied in 19 duodenal ulcer patients, 11 patients having undergone fundic superselective vagotomy for duodenal ulcer, and 10 controls. This was achieved through in vitro incorporation of tritiated thymidine in mucosal biopsies and radioautography. Except for increased fundic mucosal height, duodenal ulcer patients did not differ from controls for all parameters studied. In vagotomized patients, as compared to the other two groups, the labeling index was significantly enhanced in the innervated antral mucosa where atrophic gastritis developed, but there was no change in the labeling index and no worsening of mucosal inflammation in the denervated fundic mucosa. The only abnormality in the latter was a striking expansion, towards the surface, of the proliferative area within the fundic pit. The labeling indices and the degree of gastritis in gastric mucosae are significantly correlated in control and duodenal ulcer patients. If findings in antral mucosa, after superselective vagotomy, seemed related to gastritis lesions, those in fundic mucosa were not and may indicate an alteration due to the vagotomy per se

  3. Reappraisal of VAChT-Cre: Preference in slow motor neurons innervating type I or IIa muscle fibers.

    Science.gov (United States)

    Misawa, Hidemi; Inomata, Daijiro; Kikuchi, Miseri; Maruyama, Sae; Moriwaki, Yasuhiro; Okuda, Takashi; Nukina, Nobuyuki; Yamanaka, Tomoyuki

    2016-11-01

    VAChT-Cre.Fast and VAChT-Cre.Slow mice selectively express Cre recombinase in approximately one half of postnatal somatic motor neurons. The mouse lines have been used in various studies with selective genetic modifications in adult motor neurons. In the present study, we crossed VAChT-Cre lines with a reporter line, CAG-Syp/tdTomato, in which synaptophysin-tdTomato fusion proteins are efficiently sorted to axon terminals, making it possible to label both cell bodies and axon terminals of motor neurons. In the mice, Syp/tdTomato fluorescence preferentially co-localized with osteopontin, a recently discovered motor neuron marker for slow-twitch fatigue-resistant (S) and fast-twitch fatigue-resistant (FR) types. The fluorescence did not preferentially co-localize with matrix metalloproteinase-9, a marker for fast-twitch fatigable (FF) motor neurons. In the neuromuscular junctions, Syp/tdTomato fluorescence was detected mainly in motor nerve terminals that innervate type I or IIa muscle fibers. These results suggest that the VAChT-Cre lines are Cre-drivers that have selectivity in S and FR motor neurons. In order to avoid confusion, we have changed the mouse line names from VAChT-Cre.Fast and VAChT-Cre.Slow to VAChT-Cre.Early and VAChT-Cre.Late, respectively. The mouse lines will be useful tools to study slow-type motor neurons, in relation to physiology and pathology. © 2016 Wiley Periodicals, Inc.

  4. "Pollical palmar interosseous muscle" (musculus adductor pollicis accessorius): attachments, innervation, variations, phylogeny, and implications for human evolution and medicine.

    Science.gov (United States)

    Bello-Hellegouarch, Gaelle; Aziz, M Ashraf; Ferrero, Eva M; Kern, Michael; Francis, Nadia; Diogo, Rui

    2013-03-01

    Most atlases and textbooks dealing with human anatomy do not refer to the "pollical palmar interosseous" (PPI) muscle of Henle. In order to undertake a fresh and detailed study of this muscle and to thus better understand human comparative anatomy and evolution, we: 1) analyze the frequency of the PPI in a large sample of human hands; 2) describe the attachments, innervation and varieties of the PPI in these hands; 3) compare the data obtained with the information available in the literature; and 4) discuss the phylogenetic origin of the PPI and the implications of our observations and comparisons for medicine and for the understanding of human evolutionary history. Within the 72 hands dissected by us, the PPI is present in 67 hands (93%), commonly having a single muscular branch, originating from the medial side of the base of metacarpal I only, inserting onto the medial side of the base of the pollical proximal phalanx and/or surrounding structures (e.g., ulnar sesamoid bone, wing tendon of extensor apparatus), and passing at least partially, and usually mainly, medial to the princeps pollicis artery. A careful study of the human PPI, as well as a detailed comparison with other mammals, strongly suggest that the muscle is evolutionarily derived from the adductor pollicis, and namely from its oblique head. Therefore, we propose that PPI should be designated by the name musculus adductor pollicis accessorius, which indicates that the muscle is most likely a de novo structure derived from the adductor pollicis. Copyright © 2012 Wiley Periodicals, Inc.

  5. Risk of Damage to the Somatic Innervation of the Penis during the AdVanceProcedure: An Anatomical Study.

    Science.gov (United States)

    Hogewoning, Cornelis R C; Elzevier, Henk W; Pelger, Rob C M; Bekker, Milou D; DeRuiter, Marco C

    2015-08-01

    One of the methods to treat post radical prostatectomy stress urinary incontinence is the AdVance (American Medical Systems, Minnetonka, MN, USA) male sling procedure. During this procedure, the somatic innervation of the penis may be at risk for injury. Six AdVance procedures were performed in six donated bodies at the Anatomy and Embryology Department of the Leiden University Medical Centre. The pelves were dissected and the shortest distance between the sling and the dorsal nerve of the penis (DNP) was documented. The aim of this study was to describe the anatomical relation between the AdVance male sling and penile nerves based on the dissection of six adult male pelves. The AdVance male sling procedure was conducted in six donated male bodies. After placement, the pelves were dissected and the shortest distance between sling and the DNP was documented. The main outcome measure was the distance between the AdVance male sling and the DNP. The mean distance of the sling to the DNP was 4.1 mm and was found situated directly next to the nerve (distance 0 mm) in 4 out of 12 (33%) hemipelves. The distance of the sling to the obturator neurovascular bundle was 30 mm or more in all six bodies. Damage to the DNP caused by the AdVance male sling procedure appears to be an extremely rare complication, which has not been described in current literature. The proximity of the AdVance to the DNP could, however, pose a risk that should be taken into consideration by physicians and patients when opting for surgery. © 2015 International Society for Sexual Medicine.

  6. PrP expression, PrPSc accumulation and innervation of splenic compartments in sheep experimentally infected with scrapie.

    Directory of Open Access Journals (Sweden)

    Randi Sørby

    Full Text Available BACKGROUND: In prion disease, the peripheral expression of PrP(C is necessary for the transfer of infectivity to the central nervous system. The spleen is involved in neuroinvasion and neural dissemination in prion diseases but the nature of this involvement is not known. The present study undertook the investigation of the spatial relationship between sites of PrP(Sc accumulation, localisation of nerve fibres and PrP(C expression in the tissue compartments of the spleen of scrapie-inoculated and control sheep. METHODOLOGY/PRINCIPAL FINDINGS: Laser microdissection and quantitative PCR were used to determine PrP mRNA levels and results were compared with immunohistochemical protocols to distinguish PrP(C and PrP(Sc in tissue compartments of the spleen. In sheep experimentally infected with scrapie, the major sites of accumulation of PrP(Sc in the spleen, namely the lymphoid nodules and the marginal zone, expressed low levels of PrP mRNA. Double immunohistochemical labelling for PrP(Sc and the pan-nerve fibre marker, PGP, was used to evaluate the density of innervation of splenic tissue compartments and the intimacy of association between PrP(Sc and nerves. Some nerve fibres were observed to accompany blood vessels into the PrP(Sc-laden germinal centres. However, the close association between nerves and PrP(Sc was most apparent in the marginal zone. Other sites of close association were adjacent to the wall of the central artery of PALS and the outer rim of germinal centres. CONCLUSIONS/SIGNIFICANCE: The findings suggest that the degree of PrP(Sc accumulation does not depend on the expression level of PrP(C. Though several splenic compartments may contribute to neuroinvasion, the marginal zone may play a central role in being the compartment with most apparent association between nerves and PrP(Sc.

  7. Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb.

    Directory of Open Access Journals (Sweden)

    Rosa-Eva Huettl

    2011-02-01

    Full Text Available The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1 in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG, we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs.

  8. Thinking soap But Speaking ‘oaps’. The Sound Preparation Period: Backward Calculation From Utterance to Muscle Innervation

    Directory of Open Access Journals (Sweden)

    Nora Wiedenmann

    2010-04-01

    Full Text Available

    In this article’s model—on speech and on speech errors, dyscoordinations, and disorders—, the time-course from the muscle innervation impetuses to the utterance of sounds as intended for canonical speech sound sequences is calculated backward. This time-course is shown as the sum of all the known physiological durations of speech sounds and speech gestures that are necessary to produce an utterance. The model introduces two internal clocks, based on positive or negative factors, representing certain physiologically-based time-courses during the sound preparation period (Lautvorspann. The use of these internal clocks show that speech gestures—like other motor activities—work according to a simple serialization principle: Under non-default conditions,
    alterations of the time-courses may cause speech errors of sound serialization, dyscoordinations of sounds as observed during first language acquisition, or speech disorders as pathological cases. These alterations of the time-course are modelled by varying the two internal-clock factors. The calculation of time-courses uses as default values the sound durations of the context-dependent Munich PHONDAT Database of Spoken German (see Appendix 4. As a new, human approach, this calculation agrees mathematically with the approach of Linear Programming / Operations Research. This work gives strong support to the fairly old suspicion (of 1908 of the famous Austrian speech error scientist Meringer [15], namely that one mostly thinks and articulates in a different serialization than is audible from one’s uttered sound sequences.

  9. Neuronal uptake and metabolism of 2- and 6-fluorodopamine: false neurotransmitters for positron emission tomographic imaging of sympathetically innervated tissues

    Energy Technology Data Exchange (ETDEWEB)

    Eisenhofer, G.; Hovevey-Sion, D.; Kopin, I.J.; Miletich, R.; Kirk, K.L.; Finn, R.; Goldstein, D.S.

    1989-01-01

    The neuronal uptake and metabolism of 2-fluorodopamine (2F-dopamine), 6-fluorodopamine (6F-dopamine) and tritium-labeled dopamine were compared in heart, submaxillary gland and spleen of rats to assess the utility of 18F-labeled 2F- or 6F-dopamine for positron emission tomographic imaging of sympathetically innervated tissues. Tritiated dopamine with and without 2F- or 6F-dopamine, or tritiated 2F-dopamine alone, were injected i.v. into rats that were or were not pretreated with desipramine to block catecholamine neuronal uptake or with reserpine to block vesicular translocation of catecholamines. Tissue and plasma samples were obtained at intervals up to 1 hr after injections. At 1 hr after injection of tritiated dopamine, tritium-labeled norepinephrine, dopamine, dihydroxyphenylacetic acid and dihydroxyphenylglucol accounted for less than 2% of the tritium in plasma but up to 92% of that in tissues; tritiated norepinephrine accounted for 70% or more of the tritium in tissues. In contrast, at 1 hr after injection of tritiated 2F-dopamine, tritiated 2F-norepinephrine accounted for 30 to 46% of the tritium in tissues. Desipramine and reserpine pretreatment blocked the tissue accumulation of tritiated and fluorinated dopamine as well as their dihydroxy-metabolites, indicating that accumulation of exogenous norepinephrine and dopamine analogs was within sympathetic storage vesicles. Relative to the doses of dopamine precursors, less 2F- and 6F-norepinephrine accumulated in tissues than tritiated norepinephrine, due largely to inefficient beta-hydroxylation of fluorinated dopamine.

  10. Acid-sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain.

    Science.gov (United States)

    Fu, Hui; Fang, Peng; Zhou, Hai-Yun; Zhou, Jun; Yu, Xiao-Wei; Ni, Ming; Zheng, Jie-Yan; Jin, You; Chen, Jian-Guo; Wang, Fang; Hu, Zhuang-Li

    2016-02-01

    Orofacial pain is a common clinical symptom that is accompanied by tooth pain, migraine and gingivitis. Accumulating evidence suggests that acid-sensing ion channels (ASICs), especially ASIC3, can profoundly affect the physiological properties of nociception in peripheral sensory neurons. The aim of this study is to examine the contribution of ASICs in trigeminal ganglion (TG) neurons to orofacial inflammatory pain. A Western blot (WB), immunofluorescence assay of labelled trigeminal ganglion neurons, orofacial formalin test, cell preparation and electrophysiological experiments are performed. This study demonstrated that ASIC1, ASIC2a and ASIC3 are highly expressed in TG neurons innervating the orofacial region of rats. The amplitude of ASIC currents in these neurons increased 119.72% (for ASIC1-like current) and 230.59% (for ASIC3-like current) in the formalin-induced orofacial inflammatory pain model. In addition, WB and immunofluorescence assay demonstrated a significantly augmented expression of ASICs in orofacial TG neurons during orofacial inflammation compared with the control group. The relative protein density of ASIC1, ASIC2a and ASIC3 also increased 58.82 ± 8.92%, 45.30 ± 11.42% and 55.32 ± 14.71%, respectively, compared with the control group. Furthermore, pharmacological blockade of ASICs and genetic deletion of ASIC1 attenuated the inflammation response. These findings indicate that peripheral inflammation can induce the upregulation of ASICs in TG neurons, causing orofacial inflammatory pain. Additionally, the specific inhibitor of ASICs may have a significant analgesic effect on orofacial inflammatory pain. © 2016 John Wiley & Sons Australia, Ltd.

  11. Control of the subthalamic innervation of substantia nigra pars reticulata by D1 and D2 dopamine receptors.

    Science.gov (United States)

    Ibañez-Sandoval, Osvaldo; Hernández, Adán; Florán, Benjamin; Galarraga, Elvira; Tapia, Dagoberto; Valdiosera, Rene; Erlij, David; Aceves, Jorge; Bargas, José

    2006-03-01

    The effects of activating dopaminergic D1 and D2 class receptors of the subthalamic projections that innervate the pars reticulata of the subtantia nigra (SNr) were explored in slices of the rat brain using the whole cell patch-clamp technique. Excitatory postsynaptic currents (EPSCs) that could be blocked by 6-cyano-7-nitroquinoxalene-2,3-dione and D-(-)-2-amino-5-phosphonopentanoic acid were evoked onto reticulata GABAergic projection neurons by local field stimulation inside the subthalamic nucleus in the presence of bicuculline. Bath application of (RS)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF-38393), a dopaminergic D1-class receptor agonist, increased evoked EPSCs by approximately 30% whereas the D2-class receptor agonist, trans-(-)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo(3,4-g)quinoline (quinpirole), reduced EPSCs by approximately 25%. These apparently opposing actions were blocked by the specific D1- and D2-class receptor antagonists: R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzazepinehydrochloride (SCH 23390) and S-(-)-5-amino-sulfonyl-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride), respectively. Both effects were accompanied by changes in the paired-pulse ratio, indicative of a presynaptic site of action. The presynaptic location of dopamine receptors at the subthalamonigral projections was confirmed by mean-variance analysis. The effects of both SKF-38393 and quinpirole could be observed on terminals contacting the same postsynaptic neuron. Sulpiride and SCH 23390 enhanced and reduced the evoked EPSC, respectively, suggesting a constitutive receptor activation probably arising from endogenous dopamine. These data suggest that dopamine presynaptically modulates the subthalamic projection that targets GABAergic neurons of the SNr. Implications of this modulation for basal ganglia function are discussed.

  12. Neuronal uptake and metabolism of 2- and 6-fluorodopamine: false neurotransmitters for positron emission tomographic imaging of sympathetically innervated tissues

    International Nuclear Information System (INIS)

    Eisenhofer, G.; Hovevey-Sion, D.; Kopin, I.J.; Miletich, R.; Kirk, K.L.; Finn, R.; Goldstein, D.S.

    1989-01-01

    The neuronal uptake and metabolism of 2-fluorodopamine (2F-dopamine), 6-fluorodopamine (6F-dopamine) and tritium-labeled dopamine were compared in heart, submaxillary gland and spleen of rats to assess the utility of 18F-labeled 2F- or 6F-dopamine for positron emission tomographic imaging of sympathetically innervated tissues. Tritiated dopamine with and without 2F- or 6F-dopamine, or tritiated 2F-dopamine alone, were injected i.v. into rats that were or were not pretreated with desipramine to block catecholamine neuronal uptake or with reserpine to block vesicular translocation of catecholamines. Tissue and plasma samples were obtained at intervals up to 1 hr after injections. At 1 hr after injection of tritiated dopamine, tritium-labeled norepinephrine, dopamine, dihydroxyphenylacetic acid and dihydroxyphenylglucol accounted for less than 2% of the tritium in plasma but up to 92% of that in tissues; tritiated norepinephrine accounted for 70% or more of the tritium in tissues. In contrast, at 1 hr after injection of tritiated 2F-dopamine, tritiated 2F-norepinephrine accounted for 30 to 46% of the tritium in tissues. Desipramine and reserpine pretreatment blocked the tissue accumulation of tritiated and fluorinated dopamine as well as their dihydroxy-metabolites, indicating that accumulation of exogenous norepinephrine and dopamine analogs was within sympathetic storage vesicles. Relative to the doses of dopamine precursors, less 2F- and 6F-norepinephrine accumulated in tissues than tritiated norepinephrine, due largely to inefficient beta-hydroxylation of fluorinated dopamine

  13. Etiology and Pathogenesis of Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Samuel C. Mok

    2007-01-01

    Full Text Available Ovarian cancer is complex disease composed of different histological grades and types. However, the underlying molecular mechanisms involved in the development of different phenotypes remain largely unknown. Epidemiological studies identified multiple exogenous and endogenous risk factors for ovarian cancer development. Among them, an inflammatory stromal microenvironment seems to play a critical role in the initiation of the disease. The interaction between such a microenvironment, genetic polymorphisms, and different epithelial components such as endosalpingiosis, endometriosis, and ovarian inclusion cyst in the ovarian cortex may induce different genetic changes identified in the epithelial component of different histological types of ovarian tumors. Genetic studies on different histological grades and types provide insight into the pathogenetic pathways for the development of different disease phenotypes. However, the link between all these genetic changes and the etiological factors remains to be established.

  14. Gastrointestinal Epithelial Organoid Cultures from Postsurgical Tissues.

    Science.gov (United States)

    Hahn, Soojung; Yoo, Jongman

    2017-08-17

    An organoid is a cellular structure three-dimensionally (3D) cultured from self-organizing stem cells in vitro, which has a cell population, architectures, and organ specific functions like the originating organs. Recent advances in the 3D culture of isolated intestinal crypts or gastric glands have enabled the generation of human gastrointestinal epithelial organoids. Gastrointestinal organoids recapitulate the human in vivo physiology because of all the intestinal epithelial cell types that differentiated and proliferated from tissue resident stem cells. Thus far, gastrointestinal organoids have been extensively used for generating gastrointestinal disease models. This protocol describes the method of isolating a gland or crypt using stomach or colon tissue after surgery and establishing them into gastroids or colonoids.

  15. Fibro-epithelial hyperplasia mimicking mucocele.

    Science.gov (United States)

    Jain, K; Singh, B D; Dubey, A; Avinash, A

    2014-01-01

    The effects of chronic local irritation have been seen commonly in the form of fibroma or mucocele in children. We report a ten year old girl with the chief complaint of swelling in the lower right region of labial mucosa which was diagnosed clinically as mucocele and histologically as fibro-epithelial hyperplasia. Surgical excision was done under local anesthesia with no post-operative complication.

  16. Purinergic signalling in epithelial ion transport

    DEFF Research Database (Denmark)

    Novak, Ivana

    2011-01-01

    , including ion transport. In this review, I will first introduce the main components of the extracellular ATP signalling, which have become known as the purinergic signalling system. With more than 50 components or processes, just at cell membranes, it ranks as one of the most versatile signalling systems......-regulators of secretion. On an organ level, both receptor types can exert physiological functions and together with other partners in the purinergic signalling, integrated models for epithelial secretion and absorption are emerging....

  17. Epithelial-mesenchymal transition in breast epithelial cells treated with cadmium and the role of Snail.

    Science.gov (United States)

    Wei, Zhengxi; Shan, Zhongguo; Shaikh, Zahir A

    2018-04-01

    Epidemiological and experimental studies have implicated cadmium (Cd) with breast cancer. In breast epithelial MCF10A and MDA-MB-231 cells, Cd has been shown to promote cell growth. The present study examined whether Cd also promotes epithelial-mesenchymal transition (EMT), a hallmark of cancer progression. Human breast epithelial cells consisting of non-cancerous MCF10A, non-metastatic HCC 1937 and HCC 38, and metastatic MDA-MB-231 were treated with 1 or 3 μM Cd for 4 weeks. The MCF10A epithelial cells switched to a more mesenchymal-like morphology, which was accompanied by a decrease in the epithelial marker E-cadherin and an increase in the mesenchymal markers N-cadherin and vimentin. In both non-metastatic HCC 1937 and HCC 38 cells, treatment with Cd decreased the epithelial marker claudin-1. In addition, E-cadherin also decreased in the HCC 1937 cells. Even the mesenchymal-like MDA-MB-231 cells exhibited an increase in the mesenchymal marker vimentin. These changes indicated that prolonged treatment with Cd resulted in EMT in both normal and cancer-derived breast epithelial cells. Furthermore, both the MCF10A and MDA-MB-231 cells labeled with Zcad, a dual sensor for tracking EMT, demonstrated a decrease in the epithelial marker E-cadherin and an increase in the mesenchymal marker ZEB-1. Treatment of cells with Cd significantly increased the level of Snail, a transcription factor involved in the regulation of EMT. However, the Cd-induced Snail expression was completely abolished by actinomycin D. Luciferase reporter assay indicated that the expression of Snail was regulated by Cd at the promotor level. Snail was essential for Cd-induced promotion of EMT in the MDA-MB-231 cells, as knockdown of Snail expression blocked Cd-induced cell migration. Together, these results indicate that Cd promotes EMT in breast epithelial cells and does so by modulating the transcription of Snail. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Proteinase-activated receptor 4 stimulation-induced epithelial-mesenchymal transition in alveolar epithelial cells

    Directory of Open Access Journals (Sweden)

    Araki Hiromasa

    2007-04-01

    Full Text Available Abstract Background Proteinase-activated receptors (PARs; PAR1–4 that can be activated by serine proteinases such as thrombin and neutrophil catepsin G are known to contribute to the pathogenesis of various pulmonary diseases including fibrosis. Among these PARs, especially PAR4, a newly identified subtype, is highly expressed in the lung. Here, we examined whether PAR4 stimulation plays a role in the formation of fibrotic response in the lung, through alveolar epithelial-mesenchymal transition (EMT which contributes to the increase in myofibroblast population. Methods EMT was assessed by measuring the changes in each specific cell markers, E-cadherin for epithelial cell, α-smooth muscle actin (α-SMA for myofibroblast, using primary cultured mouse alveolar epithelial cells and human lung carcinoma-derived alveolar epithelial cell line (A549 cells. Results Stimulation of PAR with thrombin (1 U/ml or a synthetic PAR4 agonist peptide (AYPGKF-NH2, 100 μM for 72 h induced morphological changes from cobblestone-like structure to elongated shape in primary cultured alveolar epithelial cells and A549 cells. In immunocytochemical analyses of these cells, such PAR4 stimulation decreased E-cadherin-like immunoreactivity and increased α-SMA-like immunoreactivity, as observed with a typical EMT-inducer, tumor growth factor-β (TGF-β. Western blot analyses of PAR4-stimulated A549 cells also showed similar changes in expression of these EMT-related marker proteins. Such PAR4-mediated changes were attenuated by inhibitors of epidermal growth factor receptor (EGFR kinase and Src. PAR4-mediated morphological changes in primary cultured alveolar epithelial cells were reduced in the presence of these inhibitors. PAR4 stimulation increased tyrosine phosphorylated EGFR or tyrosine phosphorylated Src level in A549 cells, and the former response being inhibited by Src inhibitor. Conclusion PAR4 stimulation of alveolar epithelial cells induced epithelial

  19. Andrographolide suppresses epithelial mesenchymal transition by inhibition of MAPK signalling pathway in lens epithelial cells.

    Science.gov (United States)

    Kayastha, Forum; Johar, Kaid; Gajjar, Devarshi; Arora, Anshul; Madhu, Hardik; Ganatra, Darshini; Vasavada, Abhay

    2015-06-01

    Epithelial mesenchymal transition (EMT) of lens epithelial cells (LECs) may contribute to the development of posterior capsular opacification (PCO), which leads to visual impairment. Andrographolide has been shown to have therapeutic potential against various cancers. However, its effect on human LECs is still unknown. The purpose of this study is to evaluate the effect of andrographolide on EMT induced by growth factors in the fetal human lens epithelial cell line (FHL 124). Initially the LECs were treated with growth factors (TGF-beta 2 and bFGF) to induce EMT. Subsequently these EMT-induced cells were treated with andrographolide at 100 and 500 nM concentrations for 24 h. Our results showed that FHL 124 cells treated with growth factors had a significant decrease in protein and m-RNA levels of epithelial markers pax6 and E-Cadherin. After administering andrographolide, these levels significantly increased. It was noticed that EMT markers alpha-SMA, fibronectin and collagen IV significantly decreased after treatment with andrographolide when compared to the other group. Treatment with andrographolide significantly inhibited phosphorylation of ERK and JNK. Cell cycle analysis showed that andrographolide did not arrest cells at G0/G1 or G2/M at tested concentrations. Our findings suggest that andrographolide helps sustain epithelial characteristics by modulating EMT markers and inhibiting the mitogen-activated protein kinase (MAPK) signalling pathway in LECs. Hence it can prove to be useful in curbing EMT-mediated PCO.

  20. Gremlin Activates the Smad Pathway Linked to Epithelial Mesenchymal Transdifferentiation in Cultured Tubular Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Raquel Rodrigues-Diez

    2014-01-01

    Full Text Available Gremlin is a developmental gene upregulated in human chronic kidney disease and in renal cells in response to transforming growth factor-β (TGF-β. Epithelial mesenchymal transition (EMT is one process involved in renal fibrosis. In tubular epithelial cells we have recently described that Gremlin induces EMT and acts as a downstream TGF-β mediator. Our aim was to investigate whether Gremlin participates in EMT by the regulation of the Smad pathway. Stimulation of human tubular epithelial cells (HK2 with Gremlin caused an early activation of the Smad signaling pathway (Smad 2/3 phosphorylation, nuclear translocation, and Smad-dependent gene transcription. The blockade of TGF-β, by a neutralizing antibody against active TGF-β, did not modify Gremlin-induced early Smad activation. These data show that Gremlin directly, by a TGF-β independent process, activates the Smad pathway. In tubular epithelial cells long-term incubation with Gremlin increased TGF-β production and caused a sustained Smad activation and a phenotype conversion into myofibroblasts-like cells. Smad 7 overexpression, which blocks Smad 2/3 activation, diminished EMT changes observed in Gremlin-transfected tubuloepithelial cells. TGF-β neutralization also diminished Gremlin-induced EMT changes. In conclusion, we propose that Gremlin could participate in renal fibrosis by inducing EMT in tubular epithelial cells through activation of Smad pathway and induction of TGF-β.

  1. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

    International Nuclear Information System (INIS)

    Malizia, Andrea P.; Lacey, Noreen; Walls, Dermot; Egan, Jim J.; Doran, Peter P.

    2009-01-01

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGFβ1-mediated lytic phase. EBV lytic reactivation by TGFβ1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM 1 81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  2. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Malizia, Andrea P.; Lacey, Noreen [Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland (Ireland); Walls, Dermot [School of Biotechnology, Dublin City University. Dublin, 9. Ireland (Ireland); Egan, Jim J. [Advanced Lung Disease and Lung Transplant Program, Mater Misericordiae University Hospital. 44, Eccles Street. Dublin, 7. Ireland (Ireland); Doran, Peter P., E-mail: peter.doran@ucd.ie [Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland (Ireland)

    2009-07-01

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGF{beta}1-mediated lytic phase. EBV lytic reactivation by TGF{beta}1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM{sub 1}81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  3. Neoadjuvant Chemotherapy for Advanced Epithelial Ovarian Cancer

    International Nuclear Information System (INIS)

    Avendano Juan; Buitrago, Giancarlo; Ramos, Pedro; Suescun Oscar

    2010-01-01

    Objective: To describe the experience at the National Cancer Institute (NCI) on the use of neoadjuvant chemotherapy as primary treatment for epithelial ovarian cancer among patients in stages IIIC and IV. Methods: We conducted a descriptive retrospective study (case series type) of patients diagnosed with epithelial ovarian cancer in stages IIIC and IV, treated at the NCI from January 1, 2003 to December 31,2006, who underwent neoadjuvant chemotherapy as primary treatment. Demographic characteristics and clinical outcomes are described. Results: Seventeen patients who fulfilled the above mentioned criteria were selected. Once neoadjuvant chemotherapy ended, 5 patients (29.4%) achieved complete or partial clinical response; 4 (23.8%) remained in stable condition, and 8 (47.6%) showed signs of progressive illness. Interval debulking surgery was performed on objective response patients. Maximum cytoreduction was achieved in 5 patients (100%); first relapse was reported at month 18 of follow-up; 2 disease-free survivors were identified in December, 2007; 8 (49%) reported some degree of non-severe chemotherapy-related toxicity. No mortality was related to chemotherapy, no post surgical complications were observed and no patient required advanced support management. Conclusions: Neoadjuvant chemotherapy, followed by optimal interval debulking surgery among selected patients, can be an alternative treatment for advanced epithelial ovarian cancer among women with irresecability or the critically ill. Further studies with improved design are required to confirm these findings.

  4. Ursodeoxycholic acid attenuates colonic epithelial secretory function

    Science.gov (United States)

    Kelly, Orlaith B; Mroz, Magdalena S; Ward, Joseph B J; Colliva, Carolina; Scharl, Michael; Pellicciari, Roberto; Gilmer, John F; Fallon, Padraic G; Hofmann, Alan F; Roda, Aldo; Murray, Frank E; Keely, Stephen J

    2013-01-01

    Dihydroxy bile acids, such as chenodeoxycholic acid (CDCA), are well known to promote colonic fluid and electrolyte secretion, thereby causing diarrhoea associated with bile acid malabsorption. However, CDCA is rapidly metabolised by colonic bacteria to ursodeoxycholic acid (UDCA), the effects of which on epithelial transport are poorly characterised. Here, we investigated the role of UDCA in the regulation of colonic epithelial secretion. Cl− secretion was measured across voltage-clamped monolayers of T84 cells and muscle-stripped sections of mouse or human colon. Cell surface biotinylation was used to assess abundance/surface expression of transport proteins. Acute (15 min) treatment of T84 cells with bilateral UDCA attenuated Cl− secretory responses to the Ca2+ and cAMP-dependent secretagogues carbachol (CCh) and forskolin (FSK) to 14.0 ± 3.8 and 40.2 ± 7.4% of controls, respectively (n= 18, P acid (LCA). Accordingly, LCA (50–200 μm) enhanced agonist-induced secretory responses in vitro and a metabolically stable UDCA analogue, 6α-methyl-UDCA, exerted anti-secretory actions in vitro and in vivo. In conclusion, UDCA exerts direct anti-secretory actions on colonic epithelial cells and metabolically stable derivatives of the bile acid may offer a new approach for treating intestinal diseases associated with diarrhoea. PMID:23507881

  5. Transcriptional networks in epithelial-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Christo Venkov

    Full Text Available Epithelial-mesenchymal transition (EMT changes polarized epithelial cells into migratory phenotypes associated with loss of cell-cell adhesion molecules and cytoskeletal rearrangements. This form of plasticity is seen in mesodermal development, fibroblast formation, and cancer metastasis.Here we identify prominent transcriptional networks active during three time points of this transitional process, as epithelial cells become fibroblasts. DNA microarray in cultured epithelia undergoing EMT, validated in vivo, were used to detect various patterns of gene expression. In particular, the promoter sequences of differentially expressed genes and their transcription factors were analyzed to identify potential binding sites and partners. The four most frequent cis-regulatory elements (CREs in up-regulated genes were SRY, FTS-1, Evi-1, and GC-Box, and RNA inhibition of the four transcription factors, Atf2, Klf10, Sox11, and SP1, most frequently binding these CREs, establish their importance in the initiation and propagation of EMT. Oligonucleotides that block the most frequent CREs restrain EMT at early and intermediate stages through apoptosis of the cells.Our results identify new transcriptional interactions with high frequency CREs that modulate the stability of cellular plasticity, and may serve as targets for modulating these transitional states in fibroblasts.

  6. Flat epithelial atypia and atypical ductal hyperplasia: carcinoma underestimation rate.

    Science.gov (United States)

    Ingegnoli, Anna; d'Aloia, Cecilia; Frattaruolo, Antonia; Pallavera, Lara; Martella, Eugenia; Crisi, Girolamo; Zompatori, Maurizio

    2010-01-01

    This study was carried out to determine the underestimation rate of carcinoma upon surgical biopsy after a diagnosis of flat epithelial atypia and atypical ductal hyperplasia and 11-gauge vacuum-assisted breast biopsy. A retrospective review was conducted of 476 vacuum-assisted breast biopsy performed from May 2005 to January 2007 and a total of 70 cases of atypia were identified. Fifty cases (71%) were categorized as pure atypical ductal hyperplasia, 18 (26%) as pure flat epithelial atypia and two (3%) as concomitant flat epithelial atypia and atypical ductal hyperplasia. Each group were compared with the subsequent open surgical specimens. Surgical biopsy was performed in 44 patients with atypical ductal hyperplasia, 15 patients with flat epithelial atypia, and two patients with flat epithelial atypia and atypical ductal hyperplasia. Five cases of atypical ductal hyperplasia were upgraded to ductal carcinoma in situ, three cases of flat epithelial atypia yielded one ductal carcinoma in situ and two cases of invasive ductal carcinoma, and one case of flat epithelial atypia/atypical ductal hyperplasia had invasive ductal carcinoma. The overall rate of malignancy was 16% for atypical ductal hyperplasia (including flat epithelial atypia/atypical ductal hyperplasia patients) and 20% for flat epithelial atypia. The presence of flat epithelial atypia and atypical ductal hyperplasia at biopsy requires careful consideration, and surgical excision should be suggested.

  7. The thoracic muscular system and its innervation in third instar Calliphora vicina Larvae. II. Projection patterns of the nerves associated with the pro- and mesothorax and the pharyngeal complex.

    Science.gov (United States)

    Schoofs, Andreas; Hanslik, Ulrike; Niederegger, Senta; Heinzel, Hans-Georg; Spiess, Roland

    2010-08-01

    We describe the anatomy of the nerves that project from the central nervous system (CNS) to the pro- and mesothoracic segments and the cephalopharyngeal skeleton (CPS) for third instar Calliphora larvae. Due to the complex branching pattern we introduce a nomenclature that labels side branches of first and second order. Two fine nerves that were not yet described are briefly introduced. One paired nerve projects to the ventral arms (VAs) of the CPS. The second, an unpaired nerve, projects to the ventral surface of the cibarial part of the esophagus (ES). Both nerves were tentatively labeled after the structures they innervate. The antennal nerve (AN) innervates the olfactory dorsal organ (DO). It contains motor pathways that project through the frontal connectives (FC) to the frontal nerve (FN) and innervate the cibarial dilator muscles (CDM) which mediate food ingestion. The maxillary nerve (MN) innervates the sensory terminal organ (TO), ventral organ (VO), and labial organ (LO) and comprises the motor pathways to the mouth hook (MH) elevator, MH depressor, and the labial retractor (LR) which opens the mouth cavity. An anastomosis of unknown function exists between the AN and MN. The prothoracic accessory nerve (PaN) innervates a dorsal protractor muscle of the CPS and sends side branches to the aorta and the bolwig organ (BO) (stemmata). In its further course, this nerve merges with the prothoracic nerve (PN). The architecture of the PN is extremely complex. It innervates a set of accessory pharyngeal muscles attached to the CPS and the body wall musculature of the prothorax. Several anastomoses exist between side branches of this nerve which were shown to contain motor pathways. The mesothoracic nerve (MeN) innervates a MH accessor and the longitudinal and transversal body wall muscles of the second segment. J. Morphol. 271:969-979, 2010. (c) 2010 Wiley-Liss, Inc.

  8. Intracellular Position of Centrioles and the Direction of Homeostatic Epithelial Cell Movements in the Mouse Cornea.

    Science.gov (United States)

    Silverman, Erika; Zhao, Jin; Merriam, John C; Nagasaki, Takayuki

    2017-02-01

    Corneal epithelial cells exhibit continuous centripetal movements at a rate of about 30 µm per day, but neither the driving force nor the mechanism that determines the direction of movements is known. To facilitate the investigation of homeostatic cell movement, we examined if the intracellular position of a centriole can be used as a directional marker of epithelial cell movements in the mouse cornea. A direction of cell movements was estimated in fixed specimens from a pattern of underlying subepithelial nerve fibers. Intracellular position of centrioles was determined by gamma-tubulin immunohistology and plotted in a narrow strip along the entire diameter of a cornea from limbus to limbus. When we determined the position of centrioles in the peripheral cornea where cell movements proceed generally along a radial path, about 55% of basal epithelial cells contained a centriole in the front half of a cell. However, in the central cornea where cells exhibit a spiral pattern of movements, centrioles were distributed randomly. These results suggest that centrioles tend to be positioned toward the direction of movement in corneal basal epithelial cells when they are moving centripetally at a steady rate.

  9. Robust cell tracking in epithelial tissues through identification of maximum common subgraphs.

    Science.gov (United States)

    Kursawe, Jochen; Bardenet, Rémi; Zartman, Jeremiah J; Baker, Ruth E; Fletcher, Alexander G

    2016-11-01

    Tracking of cells in live-imaging microscopy videos of epithelial sheets is a powerful tool for investigating fundamental processes in embryonic development. Characterizing cell growth, proliferation, intercalation and apoptosis in epithelia helps us to understand how morphogenetic processes such as tissue invagination and extension are locally regulated and controlled. Accurate cell tracking requires correctly resolving cells entering or leaving the field of view between frames, cell neighbour exchanges, cell removals and cell divisions. However, current tracking methods for epithelial sheets are not robust to large morphogenetic deformations and require significant manual interventions. Here, we present a novel algorithm for epithelial cell tracking, exploiting the graph-theoretic concept of a 'maximum common subgraph' to track cells between frames of a video. Our algorithm does not require the adjustment of tissue-specific parameters, and scales in sub-quadratic time with tissue size. It does not rely on precise positional information, permitting large cell movements between frames and enabling tracking in datasets acquired at low temporal resolution due to experimental constraints such as phototoxicity. To demonstrate the method, we perform tracking on the Drosophila embryonic epidermis and compare cell-cell rearrangements to previous studies in other tissues. Our implementation is open source and generally applicable to epithelial tissues. © 2016 The Authors.

  10. Effects of dietary Na+ deprivation on epithelial Na+ channel (ENaC, BDNF, and TrkB mRNA expression in the rat tongue

    Directory of Open Access Journals (Sweden)

    Stähler Frauke

    2009-03-01

    Full Text Available Abstract Background In rodents, dietary Na+ deprivation reduces gustatory responses of primary taste fibers and central taste neurons to lingual Na+ stimulation. However, in the rat taste bud cells Na+ deprivation increases the number of amiloride sensitive epithelial Na+ channels (ENaC, which are considered as the "receptor" of the Na+ component of salt taste. To explore the mechanisms, the expression of the three ENaC subunits (α, β and γ in taste buds were observed from rats fed with diets containing either 0.03% (Na+ deprivation or 1% (control NaCl for 15 days, by using in situ hybridization and real-time quantitative RT-PCR (qRT-PCR. Since BDNF/TrkB signaling is involved in the neural innervation of taste buds, the effects of Na+ deprivation on BDNF and its receptor TrkB expression in the rat taste buds were also examined. Results In situ hybridization analysis showed that all three ENaC subunit mRNAs were found in the rat fungiform taste buds and lingual epithelia, but in the vallate and foliate taste buds, only α ENaC mRNA was easily detected, while β and γ ENaC mRNAs were much less than those in the fungiform taste buds. Between control and low Na+ fed animals, the numbers of taste bud cells expressing α, β and γ ENaC subunits were not significantly different in the fungiform, vallate and foliate taste buds, respectively. Similarly, qRT-PCR also indicated that Na+ deprivation had no effect on any ENaC subunit expression in the three types of taste buds. However, Na+ deprivation reduced BDNF mRNA expression by 50% in the fungiform taste buds, but not in the vallate and foliate taste buds. The expression of TrkB was not different between control and Na+ deprived rats, irrespective of the taste papillae type. Conclusion The findings demonstrate that dietary Na+ deprivation does not change ENaC mRNA expression in rat taste buds, but reduces BDNF mRNA expression in the fungiform taste buds. Given the roles of BDNF in survival of

  11. Chromosome aberration induction in human diploid fibroblast and epithelial cells

    International Nuclear Information System (INIS)

    Scott, D.

    1986-01-01

    The relative sensitivity of cultured human fibroblasts and epithelial cells to radiation-induced chromosomal aberrations was investigated. Lung fibroblast and kidney epithelial cells from the same fetus were compared, as were skin fibroblasts and epithelial keratinocytes from the same foreskin sample. After exposure of proliferating fetal cells to 1.5 Gy X-rays there was a very similar aberration yield in the fibroblasts and epithelial cells. Observations of either little or no difference in chromosomal sensitivity between human fibroblasts and epithelial cells give added confidence that quantitative cytogenetic data obtained from cultured fibroblasts are relevant to the question of sensitivity of epithelial cells which are the predominant cell type in human cancers. (author)

  12. Polarized protein transport and lumen formation during epithelial tissue morphogenesis.

    Science.gov (United States)

    Blasky, Alex J; Mangan, Anthony; Prekeris, Rytis

    2015-01-01

    One of the major challenges in biology is to explain how complex tissues and organs arise from the collective action of individual polarized cells. The best-studied model of this process is the cross talk between individual epithelial cells during their polarization to form the multicellular epithelial lumen during tissue morphogenesis. Multiple mechanisms of apical lumen formation have been proposed. Some epithelial lumens form from preexisting polarized epithelial structures. However, de novo lumen formation from nonpolarized cells has recently emerged as an important driver of epithelial tissue morphogenesis, especially during the formation of small epithelial tubule networks. In this review, we discuss the latest findings regarding the mechanisms and regulation of de novo lumen formation in vitro and in vivo.

  13. Functional anatomy of the hypoglossal innervated muscles of the rat tongue: a model for elongation and protrusion of the mammalian tongue.

    Science.gov (United States)

    McClung, J R; Goldberg, S J

    2000-12-01

    This anatomical investigation in the rat was designed to illustrate the detailed organization of the tongue's muscles and their innervation in order to elucidate the actions of the muscles of the higher mammalian tongue and thereby clarify the protrusor subdivision of the hypoglossal-tongue complex. The hypoglossal innervated, extrinsic styloglossus, hyoglossus, and genioglossus and the intrinsic transversus, verticalis and longitudinalis linguae muscles were observed by microdissection and analysis of serial transverse-sections of the tongue. Sihler's staining technique was applied to whole rat tongues to demonstrate the hypoglossal nerve branching patterns. Dissections of the tongue demonstrate the angles at which the extrinsic muscles act on the base of the tongue. The Sihler stained hypoglossal nerves demonstrate branches to the styloglossus and hyoglossus emanating from its lateral division while branches to the genioglossus muscle exit from its medial division. The largest portions of both XIIth nerve divisions can be seen to enter the body of the tongue to innervate the intrinsic muscles. Transverse sections of the tongue demonstrate the organization of the intrinsic muscle fibers of the tongue. Longitudinal muscle fibers run along the entire circumference of the tongue. Alternating sheets of transverse lingual and vertical lingual muscles can be observed to insert into the circumference of the tongue. Most importantly in clarifying tongue protrusion, we demonstrate the transversus muscle fibers enveloping the most superior and inferior portions of the longitudinalis muscles. Longitudinal muscle fascicles are completely encircled and thus are likely to be compressed by transverse muscle fascicles resulting in elongation of the tongue. We discuss our findings in relation to biomechanical studies, that describe the tongue as a muscular hydrostat and thereby define the "elongation-protrusion apparatus" of the mammalian tongue. In so doing, we clarify the

  14. Distinct subclassification of DRG neurons innervating the distal colon and glans penis/distal urethra based on the electrophysiological current signature.

    Science.gov (United States)

    Rau, Kristofer K; Petruska, Jeffrey C; Cooper, Brian Y; Johnson, Richard D

    2014-09-15

    Spinal sensory neurons innervating visceral and mucocutaneous tissues have unique microanatomic distribution, peripheral modality, and physiological, pharmacological, and biophysical characteristics compared with those neurons that innervate muscle and cutaneous tissues. In previous patch-clamp electrophysiological studies, we have demonstrated that small- and medium-diameter dorsal root ganglion (DRG) neurons can be subclassified on the basis of their patterns of voltage-activated currents (VAC). These VAC-based subclasses were highly consistent in their action potential characteristics, responses to algesic compounds, immunocytochemical expression patterns, and responses to thermal stimuli. For this study, we examined the VAC of neurons retrogradely traced from the distal colon and the glans penis/distal urethra in the adult male rat. The afferent population from the distal colon contained at least two previously characterized cell types observed in somatic tissues (types 5 and 8), as well as four novel cell types (types 15, 16, 17, and 18). In the glans penis/distal urethra, two previously described cell types (types 6 and 8) and three novel cell types (types 7, 14, and 15) were identified. Other characteristics, including action potential profiles, responses to algesic compounds (acetylcholine, capsaicin, ATP, and pH 5.0 solution), and neurochemistry (expression of substance P, CGRP, neurofilament, TRPV1, TRPV2, and isolectin B4 binding) were consistent for each VAC-defined subgroup. With identification of distinct DRG cell types that innervate the distal colon and glans penis/distal urethra, future in vitro studies related to the gastrointestinal and urogenital sensory function in normal as well as abnormal/pathological conditions may be benefitted. Copyright © 2014 the American Physiological Society.

  15. Remodelling of cardiac sympathetic re-innervation with thoracic spinal cord stimulation improves left ventricular function in a porcine model of heart failure.

    Science.gov (United States)

    Liao, Song-Yan; Liu, Yuan; Zuo, Mingliang; Zhang, Yuelin; Yue, Wensheng; Au, Ka-Wing; Lai, Wing-Hon; Wu, Yangsong; Shuto, Chika; Chen, Peter; Siu, Chung-Wah; Schwartz, Peter J; Tse, Hung-Fat

    2015-12-01

    Thoracic spinal cord stimulation (SCS) has been shown to improve left ventricular ejection fraction (LVEF) in heart failure (HF). Nevertheless, the optimal duration (intermittent vs. continuous) of stimulation and the mechanisms of action remain unclear. We performed chronic thoracic SCS at the level of T1-T3 (50 Hz, pulse width 0.2 ms) in 30 adult pigs with HF induced by myocardial infarction and rapid ventricular pacing for 4 weeks. All the animals were treated with daily oral metoprolol succinate (25 mg) plus ramipril (2.5 mg), and randomized to a control group (n = 10), intermittent SCS (4 h ×3, n = 10) or continuous SCS (24 h, n = 10) for 10 weeks. Serial measurements of LVEF and +dP/dt and serum levels of norepinephrine and B-type natriuretic peptide (BNP) were measured. After sacrifice, immunohistological studies of myocardial sympathetic and parasympathetic nerve sprouting and innervation were performed. Echocardiogram revealed a significant increase in LVEF and +dP/dt at 10 weeks in both the intermittent and continuous SCS group compared with controls (P < 0.05). In both SCS groups, there was diffuse sympathetic nerve sprouting over the infarct, peri-infarct, and normal regions compared with only the peri-infarct and infarct regions in the control group. In addition, sympathetic innervation at the peri-infarct and infarct regions was increased following SCS, but decreased in the control group. Myocardium norepinephrine spillover and serum BNP at 10 weeks was significantly decreased only in the continuous SCS group (P < 0.05). In a porcine model of HF, SCS induces significant remodelling of cardiac sympathetic innervation over the peri-infarct and infarct regions and is associated with improved LV function and reduced myocardial norepinephrine spillover. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  16. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia

    Directory of Open Access Journals (Sweden)

    Nagayasu Egawa

    2015-07-01

    Full Text Available Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted.

  17. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia

    Science.gov (United States)

    Egawa, Nagayasu; Egawa, Kiyofumi; Griffin, Heather; Doorbar, John

    2015-01-01

    Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted. PMID:26193301

  18. Development and Novel Uses of Antibodies in Epithelial Ovarian Cancer

    National Research Council Canada - National Science Library

    Curtin, John P

    2003-01-01

    .... Further understanding of the host response to epithelial cancers and the potential capability of innovative immunologic technologies to ovarian cancer may play a key role in therapeutic advances...

  19. Interferon-gamma sensitizes colonic epithelial cell lines to physiological and therapeutic inducers of colonocyte apoptosis.

    LENUS (Irish Health Repository)

    O'Connell, J

    2012-02-03

    Homeostasis in the colonic epithelium is achieved by a continuous cycle of proliferation and apoptosis, in which imbalances are associated with disease. Inflammatory bowel disease (IBD) and colon cancer are associated with either excessive or insufficient apoptosis of colonic epithelial cells, respectively. By using two colonic epithelial cell lines, HT29 and SW620, we investigated how the epithelial cell\\'s sensitivity to apoptosis was regulated by the proinflammatory cytokine interferon-gamma (IFN-gamma). We found that IFN-gamma sensitized HT29 cells, and to a lesser extent SW620, to diverse inducers of apoptosis of physiologic or therapeutic relevance to the colon. These apoptosis inducers included Fas (CD95\\/APO-1) ligand (FasL), short-chain fatty acids, and chemotherapeutic drugs. The extent of IFN-gamma-mediated apoptosis sensitization in these two cell lines correlated well with the degree of IFN-gamma-mediated upregulation of the proapoptotic protease caspase-1. Although IFN-gamma alone effectively sensitized HT29 cells to apoptosis, inclusion of the protein synthesis inhibitor cyclohexamide (CHX) during apoptotic challenge was necessary for maximal sensitization of SW620. The requirement of CHX to sensitize SW620 cells to apoptosis implies a need to inhibit translation of antiapoptotic proteins absent from HT29. In particular, the antiapoptotic protein Bcl-2 was strongly expressed in SW620 cells but absent from HT29. Our results indicate that IFN-gamma increases the sensitivity of colonic epithelial cells to diverse apoptotic stimuli in concert, via upregulation of caspase-1. Our findings implicate caspase-1 and Bcl-2 as important central points of control determining the general sensitivity of colonic epithelial cells to apoptosis.

  20. Traction forces exerted by epithelial cell sheets

    International Nuclear Information System (INIS)

    Saez, A; Anon, E; Ghibaudo, M; Di Meglio, J-M; Hersen, P; Ladoux, B; Du Roure, O; Silberzan, P; Buguin, A

    2010-01-01

    Whereas the adhesion and migration of individual cells have been well described in terms of physical forces, the mechanics of multicellular assemblies is still poorly understood. Here, we study the behavior of epithelial cells cultured on microfabricated substrates designed to measure cell-to-substrate interactions. These substrates are covered by a dense array of flexible micropillars whose deflection enables us to measure traction forces. They are obtained by lithography and soft replica molding. The pillar deflection is measured by video microscopy and images are analyzed with home-made multiple particle tracking software. First, we have characterized the temporal and spatial distributions of traction forces of cellular assemblies of various sizes. The mechanical force balance within epithelial cell sheets shows that the forces exerted by neighboring cells strongly depend on their relative position in the monolayer: the largest deformations are always localized at the edge of the islands of cells in the active areas of cell protrusions. The average traction stress rapidly decreases from its maximum value at the edge but remains much larger than the inherent noise due to the force resolution of our pillar tracking software, indicating an important mechanical activity inside epithelial cell islands. Moreover, these traction forces vary linearly with the rigidity of the substrate over about two decades, suggesting that cells exert a given amount of deformation rather than a force. Finally, we engineer micropatterned substrates supporting pillars with anisotropic stiffness. On such substrates cellular growth is aligned with respect to the stiffest direction in correlation with the magnitude of the applied traction forces.

  1. Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

    Science.gov (United States)

    Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2016-06-01

    Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

  2. Primitive Endoderm Differentiation: From Specification to Epithelialization.

    Science.gov (United States)

    Bassalert, Cécilia; Valverde-Estrella, Lorena; Chazaud, Claire

    2018-01-01

    At the time of implantation, the mouse blastocyst has developed three cell lineages: the epiblast (Epi), the primitive endoderm (PrE), and the trophectoderm (TE). The PrE and TE are extraembryonic tissues but their interactions with the Epi are critical to sustain embryonic growth, as well as to pattern the embryo. We review here the cellular and molecular events that lead to the production of PrE and Epi lineages and discuss the different hypotheses that are proposed for the induction of these cell types. In the second part, we report the current knowledge about the epithelialization of the PrE. © 2018 Elsevier Inc. All rights reserved.

  3. The autologus graft of epithelial tissue culture

    Directory of Open Access Journals (Sweden)

    Minaee B

    1999-08-01

    Full Text Available With the intention of research about culture and autologus graft of epithelial tissue we used 4 french Albino Rabbits with an average age of 2 months. After reproduction on the support in EMEM (Eagle's Minimum Essential Medium we used this for graft after 4 weeks. This region which grafted total replaced. After fixation of this sample and passing them through various process, histological sections were prepared. These sections were stained with H & E and masson's trichrome and studied by light microscope. We succeeded in graft. We hope in the near future by using the method of epithelium tissue culture improving to treat burned patients.

  4. Transcriptional landscape of glomerular parietal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Sina A Gharib

    Full Text Available Very little is known about the function of glomerular parietal epithelial cells (PECs. In this study, we performed genome-wide expression analysis on PEC-enriched capsulated vs. PEC-deprived decapsulated rat glomeruli to determine the transcriptional state of PECs under normal conditions. We identified hundreds of differentially expressed genes that mapped to distinct biologic modules including development, tight junction, ion transport, and metabolic processes. Since developmental programs were highly enriched in PECs, we characterized several of their candidate members at the protein level. Collectively, our findings confirm that PECs are multifaceted cells and help define their diverse functional repertoire.

  5. The role of Sox2 on lung epithelial airway epithelial differentiation

    NARCIS (Netherlands)

    J.K. Ochieng (Joshua)

    2014-01-01

    markdownabstract__Abstract__ The foregut is crucial for development of respiratory organs including the lungs. Foregut morphogenesis starts around embryonic day 8.0 in mouse when the endoderm epithelial sheet folds ventrally during gastrulation [1,2]. At embryonic day 9.0, the ventral folding

  6. Volumetric imaging of oral epithelial neoplasia by MPM-SHGM: epithelial connective tissue interface (Conference Presentation)

    Science.gov (United States)

    Pal, Rahul; Yang, Jinping; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

    2016-03-01

    The majority of oral cancers are comprised of oral squamous cell carcinoma in which neoplastic epithelial cells invade across the epithelial connective tissue interface (ECTI). Invasion is preceded by a multi-component process including epithelial hyperproliferation, loss of cell polarity, and remodeling of the extracellular matrix. Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia. In particular, volumetric imaging by these methods can reveal aspects of the 3D microstructure that are not possible by other methods and which could both further our understanding of neoplastic transformation and be explored for development of diagnostic approaches in this disease having only 55% 5-year survival rate. MPAM-SHG were applied to reveal the 3D structure of the critical ECTI interface that plays an integral part toward invasion. Epithelial dysplasia was induced in an established hamster model. MPAM-SHGM was applied to lesion sites, using 780 nm excitation (450-600nm emission) for autofluroescence of cellular and extracellular components; 840 nm using 420 nm bandpass filter for SHG. The ECTI surface was identified as the interface at which SHG signal began following the epithelium and was modeled as a 3D surface using Matlab. ECTI surface area and cell features at sites of epithelial expansion where ECTI was altered were measured; Imaged sites were biopsied and processed for histology. ROC analysis using ECTI image metrics indicated the ability to delineate normal from neoplasia with high sensitivity and specificity and it is noteworthy that inflammation did not significantly alter diagnostic potential of MPAM-SHGM .

  7. Correlation between corneal innervation and inflammation evaluated with confocal microscopy and symptomatology in patients with dry eye syndromes: a preliminary study.

    Science.gov (United States)

    Tepelus, Tudor C; Chiu, Gloria B; Huang, Jianyan; Huang, Ping; Sadda, SriniVas R; Irvine, John; Lee, Olivia L

    2017-09-01

    To evaluate corneal innervation and inflammatory cell infiltration using in vivo confocal microscopy (IVCM) and to correlate these findings with subjective symptoms of dry eye, as measured by the Ocular Surface Disease Index (OSDI) in patients with non-Sjögren's (NSDE) and Sjögren's syndrome dry eyes (SSDE). Central corneal images were prospectively captured from 10 age-matched healthy control eyes, 24 eyes with clinically diagnosed NSDE and 44 eyes with clinically diagnosed SSDE, using IVCM (HRT III RCM). Density, tortuosity and reflectivity of corneal nerves, presence of inflammatory dendritic cells (DCs) and OSDI scores were evaluated. Images obtained by IVCM from 78 eyes were analyzed. The density of nerve fibers was 1562 ± 996 μm/frame in the SSDE group, 2150 ± 1015 μm/frame in the NSDE group and 2725 ± 687 μm/frame in the control group (P eyes affected with NSDE and SSDE are characterized by alterations in corneal innervation and infiltration of inflammatory DCs. Corneal nerve density and reflectivity are correlated with severity of subjective dry eye symptoms, as measured by OSDI score.

  8. Nikolaus Rüdinger (1832-1896), His Description of Joint Innervation in 1857, and the History of Surgical Joint Denervation.

    Science.gov (United States)

    Gohritz, Andreas; Kaiser, Erich; Guggenheim, Merlin; Dellon, Arnold Lee

    2018-01-01

     Selective joint denervation has become a reliable palliative treatment, especially for painful joints in the upper and lower extremity.  This article highlights the life and work of Nikolaus Rüdinger (1832-1896) who first described joint innervation which became the basis of later techniques of surgical joint denervation. The historical evolution of this method is outlined.  Rüdinger made a unique career from apprentice barber to military surgeon and anatomy professor in Munich, Germany. His first description of articular innervation of temporomandibular, shoulder, elbow, wrist, finger, sacroiliac, hip, knee, ankle, foot, and toe joints in 1857 stimulated the subsequent history of surgical joint denervation. Comparing his investigations with modern joint denervation methods, developed by pioneers like Albrecht Wilhelm or A. Lee Dellon, shows his great exactitude and anatomical correspondence despite different current terminology. Clinical series of modern surgical joint denervations reveal success rates of up to 80% with reliable long-term results.  The history of joint denervation with Rüdinger as its important protagonist offers inspiring insights into the evolution of surgical techniques and exemplifies the value of descriptive functional anatomy, even if surgical application may not have been realized until a century later. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. Perinatal exposure to a high-fat diet is associated with reduced hepatic sympathetic innervation in one-year old male Japanese macaques.

    Directory of Open Access Journals (Sweden)

    Wilmon F Grant

    Full Text Available Our group recently demonstrated that maternal high-fat diet (HFD consumption is associated with non-alcoholic fatty liver disease, increased apoptosis, and changes in gluconeogenic gene expression and chromatin structure in fetal nonhuman primate (NHP liver. However, little is known about the long-term effects that a HFD has on hepatic nervous system development in offspring, a system that plays an important role in regulating hepatic metabolism. Utilizing immunohistochemistry and Real-Time PCR, we quantified sympathetic nerve fiber density, apoptosis, inflammation, and other autonomic components in the livers of fetal and one-year old Japanese macaques chronically exposed to a HFD. We found that HFD exposure in-utero and throughout the postnatal period (HFD/HFD, when compared to animals receiving a CTR diet for the same developmental period (CTR/CTR, is associated with a 1.7 fold decrease in periportal sympathetic innervation, a 5 fold decrease in parenchymal sympathetic innervation, and a 2.5 fold increase in hepatic apoptosis in the livers of one-year old male animals. Additionally, we observed an increase in hepatic inflammation and a decrease in a key component of the cholinergic anti-inflammatory pathway in one-year old HFD/HFD offspring. Taken together, these findings reinforce the impact that continuous exposure to a HFD has in the development of long-term hepatic pathologies in offspring and highlights a potential neuroanatomical basis for hepatic metabolic dysfunction.

  10. Anatomical study of the articular branches innervated the hip and knee joint with reference to mechanism of referral pain in hip joint disease patients.

    Science.gov (United States)

    Sakamoto, Junya; Manabe, Yoshitaka; Oyamada, Joichi; Kataoka, Hideki; Nakano, Jiro; Saiki, Kazunobu; Okamoto, Keishi; Tsurumoto, Toshiyuki; Okita, Minoru

    2018-03-25

    Referred pain in the anterior knee joint is the most common symptom in hip disease patients. The development of referred pain is considered to be related to dichotomizing peripheral sensory fibers. However, no gross anatomical findings identify any dichotomizing fibers innervating both the hip and knee joints. We dissected the femoral and obturator nerves in human cadavers to investigate the distribution of the articular branches in the hip and knee joints. Fourteen embalmed left lower limbs from 14 Japanese adult cadavers (five from females, nine from males, average age 73.8 ± 14.1 years) were observed macroscopically. The articular branches of the femoral and obturator nerves were dissected at the anterior margin of the groin toward the thigh region. After dissections of the articular nerves of the hip joints, the femoral and obturator nerves were exposed from proximally to distally to identify the articular nerves of the knee joints. The branching pattern of the articular branches in the hip and knee joints was recorded. In six of 14 limbs (42.9%), the femoral nerve supplied articular branches to the anteromedial aspect of both the hip and knee joints. These articular branches were derived from the same bundle of femoral nerve. These gross anatomical findings suggested that dichotomizing peripheral sensory fibers innervate the hip and knee joints and these could relate to the referred pain confirmed in the anterior knee joints of patients with hip disease. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  11. Nuclear microscopy of rat colon epithelial cells

    Science.gov (United States)

    Ren, M.; Rajendran, Reshmi; Ng, Mary; Udalagama, Chammika; Rodrigues, Anna E.; Watt, Frank; Jenner, Andrew Michael

    2011-10-01

    Using Nuclear microscopy, we have investigated iron distributions in the colons of Sprague Dawley rats, in order to elucidate heme uptake. Four groups of five Sprague Dawley rats (mean weight 180 g) were fed different purified diets containing either heme diet (2.5% w/w hemoglobin), high fat diet (HFD) (18% w/w fat, 1% w/w cholesterol), 'western' diet (combination of hemoglobin 2.5% and 18% fat, 1% cholesterol) or control diet (7% w/w fat). After 4 weeks, animals were sacrificed by exsanguination after anaesthesia. Thin sections of frozen colon tissue were taken, freeze dried and scanned using nuclear microscopy utilising the techniques PIXE, RBS and STIM. The new data acquisition system (IonDaq) developed in CIBA was used to obtain high resolution images and line scans were used to map the iron distributions across the colon boundaries. The nuclear microscope results indicate that when HFD is given in addition to heme, the iron content of the epithelial cells that line the colon decreases, and the zinc in the smooth muscle wall increases. This implies that the level of heme and fat in diet has an important role in colon health, possibly by influencing epithelial cells directly or changing luminal composition such as bacterial flora or levels of metabolites and cytotoxins.

  12. Nuclear microscopy of rat colon epithelial cells

    International Nuclear Information System (INIS)

    Ren, M.; Rajendran, Reshmi; Ng, Mary; Udalagama, Chammika; Rodrigues, Anna E.; Watt, Frank; Jenner, Andrew Michael

    2011-01-01

    Using Nuclear microscopy, we have investigated iron distributions in the colons of Sprague Dawley rats, in order to elucidate heme uptake. Four groups of five Sprague Dawley rats (mean weight 180 g) were fed different purified diets containing either heme diet (2.5% w/w hemoglobin), high fat diet (HFD) (18% w/w fat, 1% w/w cholesterol), 'western' diet (combination of hemoglobin 2.5% and 18% fat, 1% cholesterol) or control diet (7% w/w fat). After 4 weeks, animals were sacrificed by exsanguination after anaesthesia. Thin sections of frozen colon tissue were taken, freeze dried and scanned using nuclear microscopy utilising the techniques PIXE, RBS and STIM. The new data acquisition system (IonDaq) developed in CIBA was used to obtain high resolution images and line scans were used to map the iron distributions across the colon boundaries. The nuclear microscope results indicate that when HFD is given in addition to heme, the iron content of the epithelial cells that line the colon decreases, and the zinc in the smooth muscle wall increases. This implies that the level of heme and fat in diet has an important role in colon health, possibly by influencing epithelial cells directly or changing luminal composition such as bacterial flora or levels of metabolites and cytotoxins.

  13. Nuclear microscopy of rat colon epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Ren, M., E-mail: phyrenmq@nus.edu.sg [Centre for Ion Beam Applications (CIBA), Department of Physics, National University of Singapore, Singapore 117542 (Singapore); Rajendran, Reshmi [Lab of Molecular Imaging, Singapore Bioimaging Consotium, 11 Biopolis Way, 02-02 Helios, Singapore 138667 (Singapore); Ng, Mary [Department of Pharmacology, National University of Singapore (Singapore); Udalagama, Chammika; Rodrigues, Anna E.; Watt, Frank [Centre for Ion Beam Applications (CIBA), Department of Physics, National University of Singapore, Singapore 117542 (Singapore); Jenner, Andrew Michael [Illawara Health and Medical Research Institute (IHMRI), University of Wollongong, NSW 2522 (Australia)

    2011-10-15

    Using Nuclear microscopy, we have investigated iron distributions in the colons of Sprague Dawley rats, in order to elucidate heme uptake. Four groups of five Sprague Dawley rats (mean weight 180 g) were fed different purified diets containing either heme diet (2.5% w/w hemoglobin), high fat diet (HFD) (18% w/w fat, 1% w/w cholesterol), 'western' diet (combination of hemoglobin 2.5% and 18% fat, 1% cholesterol) or control diet (7% w/w fat). After 4 weeks, animals were sacrificed by exsanguination after anaesthesia. Thin sections of frozen colon tissue were taken, freeze dried and scanned using nuclear microscopy utilising the techniques PIXE, RBS and STIM. The new data acquisition system (IonDaq) developed in CIBA was used to obtain high resolution images and line scans were used to map the iron distributions across the colon boundaries. The nuclear microscope results indicate that when HFD is given in addition to heme, the iron content of the epithelial cells that line the colon decreases, and the zinc in the smooth muscle wall increases. This implies that the level of heme and fat in diet has an important role in colon health, possibly by influencing epithelial cells directly or changing luminal composition such as bacterial flora or levels of metabolites and cytotoxins.

  14. Epithelial-stromal interaction 1 (EPSTI1) substitutes for peritumoral fibroblasts in the tumor microenvironment

    DEFF Research Database (Denmark)

    De Neergaard, Michala; Kim, Jiyoung; Villadsen, René

    2010-01-01

    Tumor cells can activate stroma, yet the implication of this activation in terms of reciprocal induction of gene expression in tumor cells is poorly understood. Epithelial Stromal Interaction 1 (EPSTI1) is an interferon response gene originally isolated from heterotypic recombinant cultures...... of human breast cancer cells and activated breast myofibroblasts. Here we describe the first immunolocalization of EPSTI1 in normal and cancerous breast tissue, and we provide evidence for a role of this molecule in the regulation of tumor cell properties and epithelial-mesenchymal transition. In general...... cell line and silenced endogenous EPSTI1 by RNA interference in another. Irrespective of the experimental approach, EPSTI1 expression led to an increase in tumorsphere formation-a property associated with breast stem/progenitor cells. Most remarkably, we show that EPSTI1, by conveying spread of tumor...

  15. Epithelial cell-cell junctions and plasma membrane domains

    NARCIS (Netherlands)

    Giepmans, Ben N. G.; van Ijzendoorn, Sven C. D.

    Epithelial cells form a barrier against the environment, but are also required for the regulated exchange of molecules between an organism and its surroundings. Epithelial cells are characterised by a remarkable polarization of their plasma membrane, evidenced by the appearance of structurally,

  16. Epithelial calcium channels: from identification to function and regulation.

    NARCIS (Netherlands)

    Hoenderop, J.G.J.; Nilius, B.; Bindels, R.J.M.

    2003-01-01

    The epithelial calcium channels TRPV5 and TRPV6 have been studied extensively in the epithelial tissues controlling Ca(2+) homeostasis and exhibit a range of distinctive properties that distinguish them from other transient receptor potential (TRP) channels. These two novel members of the

  17. Physiological regulation of epithelial sodium channel by proteolysis

    DEFF Research Database (Denmark)

    Svenningsen, Per; Friis, Ulla G; Bistrup, Claus

    2011-01-01

    PURPOSE OF REVIEW: Activation of epithelial sodium channel (ENaC) by proteolysis appears to be relevant for day-to-day physiological regulation of channel activity in kidney and other epithelial tissues. Pathophysiogical, proteolytic activation of ENaC in kidney has been demonstrated in proteinuric...

  18. ROCK1-directed basement membrane positioning coordinates epithelial tissue polarity.

    Science.gov (United States)

    Daley, William P; Gervais, Elise M; Centanni, Samuel W; Gulfo, Kathryn M; Nelson, Deirdre A; Larsen, Melinda

    2012-01-01

    The basement membrane is crucial for epithelial tissue organization and function. However, the mechanisms by which basement membrane is restricted to the basal periphery of epithelial tissues and the basement membrane-mediated signals that regulate coordinated tissue organization are not well defined. Here, we report that Rho kinase (ROCK) controls coordinated tissue organization by restricting basement membrane to the epithelial basal periphery in developing mouse submandibular salivary glands, and that ROCK inhibition results in accumulation of ectopic basement membrane throughout the epithelial compartment. ROCK-regulated restriction of PAR-1b (MARK2) localization in the outer basal epithelial cell layer is required for basement membrane positioning at the tissue periphery. PAR-1b is specifically required for basement membrane deposition, as inhibition of PAR-1b kinase activity prevents basement membrane deposition and disrupts overall tissue organization, and suppression of PAR-1b together with ROCK inhibition prevents interior accumulations of basement membrane. Conversely, ectopic overexpression of wild-type PAR-1b results in ectopic interior basement membrane deposition. Significantly, culture of salivary epithelial cells on exogenous basement membrane rescues epithelial organization in the presence of ROCK1 or PAR-1b inhibition, and this basement membrane-mediated rescue requires functional integrin β1 to maintain epithelial cell-cell adhesions. Taken together, these studies indicate that ROCK1/PAR-1b-dependent regulation of basement membrane placement is required for the coordination of tissue polarity and the elaboration of tissue structure in the developing submandibular salivary gland.

  19. Engineering stromal-epithelial interactions in vitro for ...

    Science.gov (United States)

    Background: Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue function. Epithelial-mesenchymal interactions (EMIs) have been examined using mammalian models, ex vivo tissue recombination, and in vitro co-cultures. Although these approaches have elucidated signaling mechanisms underlying morphogenetic processes and adult mammalian epithelial tissue function, they are limited by the availability of human tissue, low throughput, and human developmental or physiological relevance. Objectives: Bioengineering strategies to promote EMIs using human epithelial and mesenchymal cells have enabled the development of human in vitro models of adult epidermal and glandular tissues. In this review, we describe recent bioengineered models of human epithelial tissue and organs that can instruct the design of organotypic models of human developmental processes.Methods: We reviewed current bioengineering literature and here describe how bioengineered EMIs have enabled the development of human in vitro epithelial tissue models.Discussion: Engineered models to promote EMIs have recapitulated the architecture, phenotype, and function of adult human epithelial tissue, and similar engineering principles could be used to develop models of developmental morphogenesis. We describe how bioengineering strategies including bioprinting and spheroid culture could be implemented to

  20. induced acute cytotoxicity in human cervical epithelial carcinoma cells

    African Journals Online (AJOL)

    Molecular basis of arsenite (As +3 )-induced acute cytotoxicity in human cervical epithelial carcinoma cells. ... Libyan Journal of Medicine ... Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and ...

  1. Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology

    Energy Technology Data Exchange (ETDEWEB)

    Lasalvia, Maria [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Castellani, Stefano [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy); D’Antonio, Palma [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Perna, Giuseppe [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Carbone, Annalucia [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy); Colia, Anna Laura; Maffione, Angela Bruna [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Capozzi, Vito [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Conese, Massimo, E-mail: massimo.conese@unifg.it [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy)

    2016-10-15

    The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module. Moreover, we also sought to determine whether disorganization of actin cytoskeleton is linked to hypersoption of apical fluid. Not only CFBE41o- (CFBE) cells, immortalized airway epithelial cells homozygous for the F508del CFTR allele, showed a different morphology in comparison with 16HBE14o- (16HBE) epithelial cells, wild-type for CFTR, but also they displayed a lack of stress fibers, suggestive of a disorganized actin cytoskeleton. AFM measurements showed that CFBE cells presented a higher membrane roughness and decreased rigidity as compared with 16HBE cells. CFBE overexpressing wtCFTR became more elongated than the parental CFBE cell line and presented actin stress fibers. CFBE cells absorbed more fluid from the apical compartment. Study of fluid absorption with the F-actin-depolymerizing agent Latrunculin B demonstrated that actin cytoskeletal disorganization increased fluid absorption, an effect observed at higher magnitude in 16HBE than in CFBE cells. For the first time, we demonstrate that actin cytoskeleton disorganization is reflected by AFM parameters in CF airway epithelial cells. Our data also strongly suggest that the lack of stress fibers is involved in at least one of the early step in CF pathophysiology at the levels of the airways, i.e. fluid hypersorption. - Highlights: • CF bronchial epithelial (CFBE) cells show a disorganized actin cytoskeleton. • CFBE cells present high roughness and low rigidity in

  2. Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology

    International Nuclear Information System (INIS)

    Lasalvia, Maria; Castellani, Stefano; D’Antonio, Palma; Perna, Giuseppe; Carbone, Annalucia; Colia, Anna Laura; Maffione, Angela Bruna; Capozzi, Vito; Conese, Massimo

    2016-01-01

    The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module. Moreover, we also sought to determine whether disorganization of actin cytoskeleton is linked to hypersoption of apical fluid. Not only CFBE41o- (CFBE) cells, immortalized airway epithelial cells homozygous for the F508del CFTR allele, showed a different morphology in comparison with 16HBE14o- (16HBE) epithelial cells, wild-type for CFTR, but also they displayed a lack of stress fibers, suggestive of a disorganized actin cytoskeleton. AFM measurements showed that CFBE cells presented a higher membrane roughness and decreased rigidity as compared with 16HBE cells. CFBE overexpressing wtCFTR became more elongated than the parental CFBE cell line and presented actin stress fibers. CFBE cells absorbed more fluid from the apical compartment. Study of fluid absorption with the F-actin-depolymerizing agent Latrunculin B demonstrated that actin cytoskeletal disorganization increased fluid absorption, an effect observed at higher magnitude in 16HBE than in CFBE cells. For the first time, we demonstrate that actin cytoskeleton disorganization is reflected by AFM parameters in CF airway epithelial cells. Our data also strongly suggest that the lack of stress fibers is involved in at least one of the early step in CF pathophysiology at the levels of the airways, i.e. fluid hypersorption. - Highlights: • CF bronchial epithelial (CFBE) cells show a disorganized actin cytoskeleton. • CFBE cells present high roughness and low rigidity in the

  3. Silk Film Topography Directs Collective Epithelial Cell Migration

    Science.gov (United States)

    Rosenblatt, Mark I.

    2012-01-01

    The following study provides new insight into how surface topography dictates directed collective epithelial cell sheet growth through the guidance of individual cell movement. Collective cell behavior of migrating human corneal limbal-epithelial cell sheets were studied on highly biocompatible flat and micro-patterned silk film surfaces. The silk film edge topography guided the migratory direction of individual cells making up the collective epithelial sheet, which resulted in a 75% increase in total culture elongation. This was due to a 3-fold decrease in cell sheet migration rate efficiency for movement perpendicular to the topography edge. Individual cell migration direction is preferred in the parallel approach to the edge topography where localization of cytoskeletal proteins to the topography’s edge region is reduced, which results in the directed growth of the collective epithelial sheet. Findings indicate customized biomaterial surfaces may be created to direct both the migration rate and direction of tissue epithelialization. PMID:23185573

  4. Crossroads of Wnt and Hippo in epithelial tissues.

    Science.gov (United States)

    Bernascone, Ilenia; Martin-Belmonte, Fernando

    2013-08-01

    Epithelial tissues undergo constant growth and differentiation during embryonic development and to replace damaged tissue in adult organs. These processes are governed by different signaling pathways that ultimately control the expression of genes associated with cell proliferation, patterning, and death. One essential pathway is Wnt, which controls tubulogenesis in several epithelial organs. Recently, Wnt has been closely linked to other signaling pathways, such as Hippo, that orchestrate proliferation and apoptosis to control organ size. There is evidence that epithelial cell junctions may sequester the transcription factors that act downstream of these signaling pathways, which would represent an important aspect of their functional regulation and their influence on cell behavior. Here, we review the transcriptional control exerted by the Wnt and Hippo signaling pathways during epithelial growth, patterning, and differentiation and recent advances in understanding of the regulation and crosstalk of these pathways in epithelial tissues. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Paradigm Shift in the Management Strategy for Epithelial Ovarian Cancer.

    Science.gov (United States)

    Fujiwara, Keiichi; McAlpine, Jessica N; Lheureux, Stephanie; Matsumura, Noriomi; Oza, Amit M

    2016-01-01

    The hypothesis on the pathogenesis of epithelial ovarian cancer continues to evolve. Although epithelial ovarian cancer had been assumed to arise from the coelomic epithelium of the ovarian surface, it is now becoming clearer that the majority of serous carcinomas arise from epithelium of the distal fallopian tube, whereas clear cell and endometrioid cancers arise from endometriosis. Molecular and genomic characteristics of epithelial ovarian cancer have been extensively investigated. Our understanding of pathogenesis of the various histologic types of ovarian cancer have begun to inform changes to the strategies for management of epithelial ovarian cancer, which represent a paradigm shift not only for treatment but also for prevention, which previously had not been considered achievable. In this article, we will discuss novel attempts at the prevention of high-grade serous ovarian cancer and treatment strategies for two distinct entities in epithelial ovarian cancer: low-grade serous and clear cell ovarian carcinomas, which are relatively rare and resistant to conventional chemotherapy.

  6. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment......ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment...

  7. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment......ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment...

  8. Globoside accelerates the differentiation of dental epithelial cells into ameloblasts

    Institute of Scientific and Technical Information of China (English)

    Takashi Nakamura; Yuta Chiba; Masahiro Naruse; Kan Saito; Hidemitsu Harada; Satoshi Fukumoto

    2016-01-01

    Tooth crown morphogenesis is tightly regulated by the proliferation and differentiation of dental epithelial cells. Globoside (Gb4), a globo-series glycosphingolipid, is highly expressed during embryogenesis as well as organogenesis, including tooth development. We previously reported that Gb4 is dominantly expressed in the neutral lipid fraction of dental epithelial cells. However, because its functional role in tooth development remains unknown, we investigated the involvement of Gb4 in dental epithelial cell differentiation. The expression of Gb4 was detected in ameloblasts of postnatal mouse molars and incisors. A cell culture analysis using HAT-7 cells, a rat-derived dental epithelial cell line, revealed that Gb4 did not promote dental epithelial cell proliferation. Interestingly, exogenous administration of Gb4 enhanced the gene expression of enamel extracellular matrix proteins such as ameloblastin, amelogenin, and enamelin in dental epithelial cells as well as in developing tooth germs. Gb4 also induced the expression of TrkB, one of the key receptors required for ameloblast induction in dental epithelial cells. In contrast, Gb4 downregulated the expression of p75, a receptor for neurotrophins (including neurotrophin-4) and a marker of undifferentiated dental epithelial cells. In addition, we found that exogenous administration of Gb4 to dental epithelial cells stimulated the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase signalling pathways. Furthermore, Gb4 induced the expression of epiprofin and Runx2, the positive regulators for ameloblastin gene transcription. Thus, our results suggest that Gb4 contributes to promoting the differentiation of dental epithelial cells into ameloblasts.

  9. Epstein–Barr virus (EBV-associated epithelial and non-epithelial lesions of the oral cavity

    Directory of Open Access Journals (Sweden)

    Kentaro Kikuchi

    2017-08-01

    Full Text Available Epstein–Barr virus (EBV is known to be associated with the development of malignant lymphoma and lymphoproliferative disorders (LPDs in immunocompromised patients. EBV, a B-lymphotropic gamma-herpesvirus, causes infectious mononucleosis and oral hairy leukoplakia, as well as various pathological types of lymphoid malignancy. Furthermore, EBV is associated with epithelial malignancies such as nasopharyngeal carcinoma (NPC, salivary gland tumor, gastric carcinoma and breast carcinoma. In terms of oral disease, there have been several reports of EBV-related oral squamous cell carcinoma (OSCC worldwide. However, the role of EBV in tumorigenesis of human oral epithelial or lymphoid tissue is unclear. This review summarizes EBV-related epithelial and non-epithelial tumors or tumor-like lesions of the oral cavity. In addition, we describe EBV latent genes and their expression in normal epithelium, inflamed gingiva, epithelial dysplasia and SCC, as well as considering LPDs (MTX- and age-related and DLBCLs of the oral cavity.

  10. Turbulent Dynamics of Epithelial Cell Cultures

    Science.gov (United States)

    Blanch-Mercader, C.; Yashunsky, V.; Garcia, S.; Duclos, G.; Giomi, L.; Silberzan, P.

    2018-05-01

    We investigate the large length and long time scales collective flows and structural rearrangements within in vitro human bronchial epithelial cell (HBEC) cultures. Activity-driven collective flows result in ensembles of vortices randomly positioned in space. By analyzing a large population of vortices, we show that their area follows an exponential law with a constant mean value and their rotational frequency is size independent, both being characteristic features of the chaotic dynamics of active nematic suspensions. Indeed, we find that HBECs self-organize in nematic domains of several cell lengths. Nematic defects are found at the interface between domains with a total number that remains constant due to the dynamical balance of nucleation and annihilation events. The mean velocity fields in the vicinity of defects are well described by a hydrodynamic theory of extensile active nematics.

  11. Pten Regulates Epithelial Cytodifferentiation during Prostate Development

    DEFF Research Database (Denmark)

    Lokody, Isabel B; Francis, Jeffrey C; Gardiner, Jennifer R

    2015-01-01

    that are shared with Pten mutant prostate cancer models, including a decrease in androgen receptor regulated genes. In depth analysis of the phenotype of these mice during development revealed that loss of Pten leads to the precocious differentiation of epithelial cells towards a luminal cell fate. This study......Gene expression and functional studies have indicated that the molecular programmes involved in prostate development are also active in prostate cancer. PTEN has been implicated in human prostate cancer and is frequently mutated in this disease. Here, using the Nkx3.1:Cre mouse strain and a genetic...... deletion approach, we investigate the role of Pten specifically in the developing mouse prostate epithelia. In contrast to its role in other developing organs, this gene is dispensable for the initial developmental processes such as budding and branching. However, as cytodifferentiation progresses...

  12. Rat glomerular epithelial cells in culture. Parietal or visceral epithelial origin

    International Nuclear Information System (INIS)

    Norgaard, J.O.

    1987-01-01

    Isolated glomeruli from rats were explanted under standard culture conditions and outgrowths were studied by light and electron microscopy in order to identify the cells. Rat glomerular samples contained 20 to 30% structurally well-preserved encapsulated glomeruli which had a large rate of attachment to the substrate and very constantly gave rise to cellular outgrowth. In order to label cells from which outgrowth originated the glomerular incorporation of [ 3 H]thymidine was studied in the preattachment phase. By light and electron microscope autoradiograph it was demonstrated that label was located only over visceral and parietal epithelial cells during the first 3 days of culture. Incorporation of [ 3 H]thymidine was seen in mesangial cells after 5 days, i.e., after the glomeruli had attached to the culture vessels and the initial outgrowth had appeared. Consequently the first cells to grow out were of epithelial origin. Glomeruli were then incubated with [ 3 H]thymidine for the first 2 1/2 days of culture in order to label the epithelial cells, then were allowed to attach to the substrate and induce cell outgrowth. By light microscope autoradiography performed with the outgrowths in situ two types of cells with labeled nuclei were seen: (a) a small, polyhedral ciliated cell which grew in colonies where the cells were joined by junctional complexes (type I), and (b) a second very large, often multinucleated cell (type II). Based on the structural resemblance with their counterparts in situ and on comparisons with positively identified visceral epithelial cells in outgrowths from other species it is suggested that type I cells are derived from the parietal epithelium of Bowman's capsule and type II cells from the visceral epithelium

  13. The human airway epithelial basal cell transcriptome.

    Directory of Open Access Journals (Sweden)

    Neil R Hackett

    2011-05-01

    Full Text Available The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population.Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels.The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium.

  14. Epithelial topography for repetitive tooth formation

    Directory of Open Access Journals (Sweden)

    Marcia Gaete

    2015-12-01

    Full Text Available During the formation of repetitive ectodermally derived organs such as mammary glands, lateral line and teeth, the tissue primordium iteratively initiates new structures. In the case of successional molar development, new teeth appear sequentially in the posterior region of the jaw from Sox2+ cells in association with the posterior aspect of a pre-existing tooth. The sequence of molar development is well known, however, the epithelial topography involved in the formation of a new tooth is unclear. Here, we have examined the morphology of the molar dental epithelium and its development at different stages in the mouse in vivo and in molar explants. Using regional lineage tracing we show that within the posterior tail of the first molar the primordium for the second and third molar are organized in a row, with the tail remaining in connection with the surface, where a furrow is observed. The morphology and Sox2 expression of the tail retains characteristics reminiscent of the earlier stages of tooth development, such that position along the A-P axes of the tail correlates with different temporal stages. Sox9, a stem/progenitor cell marker in other organs, is expressed mainly in the suprabasal epithelium complementary with Sox2 expression. This Sox2 and Sox9 expressing molar tail contains actively proliferating cells with mitosis following an apico-basal direction. Snail2, a transcription factor implicated in cell migration, is expressed at high levels in the tip of the molar tail while E-cadherin and laminin are decreased. In conclusion, our studies propose a model in which the epithelium of the molar tail can grow by posterior movement of epithelial cells followed by infolding and stratification involving a population of Sox2+/Sox9+ cells.

  15. [The molecular biology of epithelial ovarian cancer].

    Science.gov (United States)

    Leary, Alexandra; Pautier, Patricia; Tazi, Youssef; Morice, Philippe; Duvillard, Pierre; Gouy, Sébastien; Uzan, Catherine; Gauthier, Hélène; Balleyguier, Corinne; Lhommé, Catherine

    2012-12-01

    Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research.

  16. Solo and keratin filaments regulate epithelial tubule morphology.

    Science.gov (United States)

    Nishimura, Ryosuke; Kato, Kagayaki; Fujiwara, Sachiko; Ohashi, Kazumasa; Mizuno, Kensaku

    2018-04-28

    Epithelial tubules, consisting of the epithelial cell sheet with a central lumen, are the basic structure of many organs. Mechanical forces play an important role in epithelial tubulogenesis; however, little is known about the mechanisms controlling the mechanical forces during epithelial tubule morphogenesis. Solo (also known as ARHGEF40) is a RhoA-targeting guanine-nucleotide exchange factor that is involved in mechanical force-induced RhoA activation and stress fiber formation. Solo binds to keratin-8/keratin-18 (K8/K18) filaments, and this interaction plays a crucial role in mechanotransduction. In this study, we examined the roles of Solo and K8/K18 filaments in epithelial tubulogenesis using MDCK cells cultured in 3D collagen gels. Knockdown of either Solo or K18 resulted in rounder tubules with increased lumen size, indicating that Solo and K8/K18 filaments play critical roles in forming the elongated morphology of epithelial tubules. Moreover, knockdown of Solo or K18 decreased the level of diphosphorylated myosin light chain (a marker of contractile force) at the luminal and outer surfaces of tubules, suggesting that Solo and K8/K18 filaments are involved in the generation of the myosin II-mediated contractile force during epithelial tubule morphogenesis. In addition, K18 filaments were normally oriented along the long axis of the tubule, but knockdown of Solo perturbed their orientation. These results suggest that Solo plays crucial roles in forming the elongated morphology of epithelial tubules and in regulating myosin II activity and K18 filament organization during epithelial tubule formation.

  17. Epithelial cells as alternative human biomatrices for comet assay.

    Science.gov (United States)

    Rojas, Emilio; Lorenzo, Yolanda; Haug, Kristiane; Nicolaissen, Bjørn; Valverde, Mahara

    2014-01-01

    The comet assay is a valuable experimental tool aimed at mapping DNA damage in human cells in vivo for environmental and occupational monitoring, as well as for therapeutic purposes, such as storage prior to transplant, during tissue engineering, and in experimental ex vivo assays. Furthermore, due to its great versatility, the comet assay allows to explore the use of alternative cell types to assess DNA damage, such as epithelial cells. Epithelial cells, as specialized components of many organs, have the potential to serve as biomatrices that can be used to evaluate genotoxicity and may also serve as early effect biomarkers. Furthermore, 80% of solid cancers are of epithelial origin, which points to the importance of studying DNA damage in these tissues. Indeed, studies including comet assay in epithelial cells have either clear clinical applications (lens and corneal epithelial cells) or examine genotoxicity within human biomonitoring and in vitro studies. We here review improvements in determining DNA damage using the comet assay by employing lens, corneal, tear duct, buccal, and nasal epithelial cells. For some of these tissues invasive sampling procedures are needed. Desquamated epithelial cells must be obtained and dissociated prior to examination using the comet assay, and such procedures may induce varying amounts of DNA damage. Buccal epithelial cells require lysis enriched with proteinase K to obtain free nucleosomes. Over a 30 year period, the comet assay in epithelial cells has been little employed, however its use indicates that it could be an extraordinary tool not only for risk assessment, but also for diagnosis, prognosis of treatments and diseases.

  18. Generalized functions

    CERN Document Server

    Gelfand, I M; Graev, M I; Vilenkin, N Y; Pyatetskii-Shapiro, I I

    Volume 1 is devoted to basics of the theory of generalized functions. The first chapter contains main definitions and most important properties of generalized functions as functional on the space of smooth functions with compact support. The second chapter talks about the Fourier transform of generalized functions. In Chapter 3, definitions and properties of some important classes of generalized functions are discussed; in particular, generalized functions supported on submanifolds of lower dimension, generalized functions associated with quadratic forms, and homogeneous generalized functions are studied in detail. Many simple basic examples make this book an excellent place for a novice to get acquainted with the theory of generalized functions. A long appendix presents basics of generalized functions of complex variables.

  19. CD8+ T cells induce thyroid epithelial cell hyperplasia and fibrosis.

    Science.gov (United States)

    Yu, Shiguang; Fang, Yujiang; Sharav, Tumenjargal; Sharp, Gordon C; Braley-Mullen, Helen

    2011-02-15

    CD8(+) T cells can be important effector cells in autoimmune inflammation, generally because they can damage target cells by cytotoxicity. This study shows that activated CD8(+) T cells induce thyroid epithelial cell hyperplasia and proliferation and fibrosis in IFN-γ(-/-) NOD.H-2h4 SCID mice in the absence of CD4(+) T cells. Because CD8(+) T cells induce proliferation rather than cytotoxicity of target cells, these results describe a novel function for CD8(+) T cells in autoimmune disease. In contrast to the ability of purified CD8(+) T cells to induce thyrocyte proliferation, CD4(+) T cells or CD8 T cell-depleted splenocytes induced only mild thyroid lesions in SCID recipients. T cells in both spleens and thyroids highly produce TNF-α. TNF-α promotes proliferation of thyrocytes in vitro, and anti-TNF-α inhibits development of thyroid epithelial cell hyperplasia and proliferation in SCID recipients of IFN-γ(-/-) splenocytes. This suggests that targeting CD8(+) T cells and/or TNF-α may be effective for treating epithelial cell hyperplasia and fibrosis.

  20. Anterograde axonal transport and intercellular transfer of WGA-HRP in trigeminal-innervated sensory receptors of rat incisive papilla.

    Science.gov (United States)

    Chan, K Y; Byers, M R

    1985-04-08

    The ultrastructure and identification of WGA-HRP-labeled sensory receptors in the rat incisive papilla (the most anterior part of hard palate) were studied using semiserial thin sections. Various sensory receptors were organized according to three locations: dome region (ventral), chemosensory corpuscle region (medial to orifice of incisive canal), and lateral labium (apposing the incisive canal). In the dome region, the sensory receptors were localized in three sensory zones that were associated with surface ridges (one medial and two lateral). In each of these zones, intraepithelial receptor axons and Merkel receptors occurred in the epithelium, while simple unencapsulated corpuscles, glomerular-Meissner corpuscles, and incisive (encapsulated) corpuscles occurred in the lamina propria. In the chemosensory corpuscle region, chemosensory corpuscles and intraepithelial receptor axons were located in the epithelium, and incisive corpuscles were present in the lamina propria. In the lateral labium, only intraepithelial receptor axons were prominent. In all these sensory receptors, the preterminal axons and axon terminals were labeled with the tracer protein. In addition, some nonneuronal cells closely associated with the axon terminals were selectively labeled, e.g., terminal Schwann cells, lamellar Schwann cells, Merkel cells, corpuscular basal cells and chemosensory cells. Other adjacent cells were not labeled, e.g., unspecialized epithelial cells, capsular cells, corpuscular sustentacular cells, and fibroblasts. In both labeled axons and cells, WGA-HRP was incorporated into vesicles, tubules, and vacuolar organelles. The specific intercellular transfer of tracer protein may indicate trophic interactions between axon terminals and support cells in sensory receptors. The specific organization of multiple sensory receptors in the rat incisive papilla may provide a useful alternative system for studying somatosensory physiology.

  1. Lymphangioma circumscriptum, angiokeratoma, or superficial vascular ectasia with epithelial hyperplasia?

    Science.gov (United States)

    Katsoulas, Nikolaos; Tosios, Konstantinos I; Argyris, Prokopios; Koutlas, Ioannis G; Sklavounou, Alexandra

    2014-08-01

    We report a case of lymphangioma circumscriptum (cavernous lymphangioma with epithelial hyperplasia) in a 12-year-old girl, presenting as a papillary tumor on the right dorsal side of her tongue. Microscopic examination found cavernous vascular channels lined by a single layer of CD31(+), podoplanin-positive, CD34(-) endothelial cells that occupied the papillary lamina propria and were accompanied by epithelial hyperplasia. A review of the literature on oral vascular tumors with epithelial hyperplasia, namely, lymphangioma circumscriptum and angiokeratoma, provided information that draws into question the use of these terms. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Use of mammary epithelial antigens as markers in mammary neoplasia

    International Nuclear Information System (INIS)

    Ceriani, R.L.; Peterson, J.A.; Blank, E.W.

    1979-01-01

    Cell-type specific antigens of the mammary epithelial cells can be used as markers of breast neoplasia. Methods are proposed for the detection of metastatic mammary tissue in vivo by injection of [ 125 I]-labeled antibodies against the mammary epithelial antigens. In addition, the reduced expression of mammary epithelial cell antigens in neoplastic breast cells, quantitated here on a cell per cell basis by flow cytofluorimetry, is a marker of neoplasia and an indication of a deletion accompanying the neoplastic transformation of these cells. (Auth.)

  3. No junctional communication between epithelial cells in hydra

    DEFF Research Database (Denmark)

    de Laat, S W; Tertoolen, L G; Grimmelikhuijzen, C J

    1980-01-01

    junctions between epithelial cells of hydra. However, until now, there has been no report published on whether these junctions enable the epithelial cells to exchange molecules of small molecular weight, as has been described in other organisms. Therefore we decided to investigate the communicative...... properties of the junctional membranes by electrophysiological methods and by intracellular-dye iontophoresis. We report here that no electrotonic coupling is detectable between epithelial cells of Hydra attenuata in: (1) intact animals, (2) head-regenerating animals, (3) cell re-aggregates, and (4) hydra...

  4. The glossopharyngeal nerve controls epithelial expression of Sprr2a and Krt13 around taste buds in the circumvallate papilla.

    Science.gov (United States)

    Miura, Hirohito; Kusakabe, Yuko; Hashido, Kento; Hino, Akihiro; Ooki, Makoto; Harada, Shuitsu

    2014-09-19

    Tastants reach the tip of taste bud cells through taste pores which are openings in the epithelium. We found Sprr2a is selectively expressed in the upper layer of the epithelium surrounding taste buds in the circumvallate papilla (CV) where the epithelium is organized into taste pores. Sprr2a is a member of a small proline-rich protein family, which is suggested to be involved in the restitution/migration phase of epithelial wound healing. The expression of Sprr2a was restricted to the upper layer and largely segregated with Ptch1 expression that is restricted to the basal side of the epithelium around the taste buds. Denervation resulted in the gradual loss of Sprr2a-expressing cells over 10 days similarly to that of taste bud cells which is in contrast to the rapid loss of Ptch1 expression. We also found that denervation caused an increase of Keratin (Krt)13 expression around taste buds that corresponded with the disappearance of Sprr2a and Ptch1 expression. Taste buds were surrounded by Krt13-negative cells in the CV in control mice. However, at 6 days post-denervation, taste buds were tightly surrounded by Krt13-positive cells. During taste bud development, taste bud cells emerged together with Krt13-negtive cells, and Sprr2a expression was increased along with the progress of taste bud development. These results demonstrate that regional gene expression surrounding taste buds is associated with taste bud formation and controlled by the innervating taste nerve. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Postnatal remodeling of the neural components of the epithelial-mesenchymal trophic unit in the proximal airways of infant rhesus monkeys exposed to ozone and allergen

    International Nuclear Information System (INIS)

    Larson, Shawnessy D.; Schelegle, Edward S.; Walby, William F.; Gershwin, Laural J.; Fanuccihi, Michelle V.; Evans, Michael J.; Joad, Jesse P.; Tarkington, Brian K.; Hyde, Dallas M.; Plopper, Charles G.

    2004-01-01

    Nerves and neuroendocrine cells located within the airway epithelium are ideally situated to sample a changing airway environment, to transmit that information to the central nervous system, and to promote trophic interactions between epithelial and mesenchymal cellular and acellular components. We tested the hypothesis that the environmental stresses of ozone (O 3 ) and house dust mite allergen (HDMA) in atopic infant rhesus monkeys alter the distribution of airway nerves. Midlevel bronchi and bronchioles from 6-month-old infant monkeys that inhaled filtered air (FA), house dust mite allergen HDMA, O 3 , or HDMA + O 3 for 11 episodes (5 days each, 0.5 ppm O 3 , 8 h/day followed by 9 days recovery) were examined using immunohistochemistry for the presence of Protein gene product 9.5 (PGP 9.5), a nonspecific neural indicator, and calcitonin gene-related peptide (CGRP). Along the axial path between the sixth and the seventh intrapulmonary airway generations, there were small significant (P 3 , while in monkeys exposed to HDMA + O 3 there was a greater significant (P 3 or HDMA + O 3 there was a significant increase in the number of PGP 9.5 positive/CGRP negative cells that were anchored to the basal lamina and emitted projections in primarily the lateral plain and often intertwined with projections and cell bodies of other similar cells. We conclude that repeated cycles of acute injury and repair associated with the episodic pattern of ozone and allergen exposure alter the normal development of neural innervation of the epithelial compartment and the appearance of a new population of undefined PGP 9.5 positive cells within the epithelium

  6. Lesions of the dopaminergic innervation of the nucleus accumbens medial shell delay the generation of preference for sucrose, but not of sexual pheromones.

    Science.gov (United States)

    Martínez-Hernández, José; Lanuza, Enrique; Martínez-García, Fernando

    2012-01-15

    Male sexual pheromones are rewarding stimuli for female mice, able to induce conditioned place preference. To test whether processing these natural reinforcing stimuli depends on the dopaminergic innervation of the nucleus accumbens, as for other natural rewards, we compare the effects of specific lesions of the dopaminergic innervation of the medial shell of the nucleus accumbens on two different appetitive behaviours, 'pheromone seeking' and sucrose preferential intake. Female mice, with no previous experience with either adult male chemical stimuli or with sucrose, received injections of 6-hydroxydopamine (or vehicle) in the medial shell of the accumbens. Then, we analyzed their preference for male soiled-bedding and their preferential intake of a sucrose solution, with particular emphasis on the dynamics of acquisition of both natural rewards. The results indicate that both lesioned and sham animals showed similar preference for male sexual pheromones, which was constant along the test (linear dynamics). In contrast, lesioned animals differed from sham operated mice in the dynamics of sucrose consumption in their first test of sucrose preference. Sham animals showed an initial sucrose preference followed by preference for water, which can be interpreted as sucrose neophobia. Lesioned animals showed no preference at the beginning of the test, and a delayed sucrose preference appeared followed by a delayed neophobia. The next day, during a second sucrose-preference test, both groups displayed comparable and sustained preferential sucrose intake. Therefore, dopamine in the medial shell of the nucleus accumbens has a different role on the reward of sexual pheromones and sucrose. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Experimental study of motor nerve innervation of uvala muscle%悬雍垂肌运动神经支配的实验研究

    Institute of Scientific and Technical Information of China (English)

    仲维剑; 张奎启; 王宏青

    2001-01-01

    目的探讨悬雍垂肌运动神经来源及走行路径。方法以家兔为研究对象,应用辣根过氧化物酶(horseridish peroxidase,HRP)逆行追踪技术,配合使用颅内的脑神经根切断术。结果悬雍垂肌的运动神经元位于同侧疑核中;切断一侧副神经延脑根后,疑核内的标记神经元消失。结论悬雍垂肌是疑核内运动神经元的轴突,经副神经延脑根出颅,再经由迷走神经咽支进行支配。%Objective To investigate the motor nerve innervation of uvala muscle. Methods Horseridish peroxidase (HRP) retrograde tracing technique was used in conjunction with selective intracranial severing of cranial nerve rootlets in 8 rabbies. Results Following HRP injection into uvala muscles, labeled motoneurons were located in the rostral section of nucleus ambiguus. No labeled motoneurons were found in the facial nucleus. Labled motoneurons were ipslaterally abolished after the cranial rootlets of accessory nerve on one side were intracranially severed. Conclusions Uvala muscles are innervated by the motoneurons in the nucleus ambiguus. The axons of those motoneurons come out of the cranium through the cranial rootlet of the accessory nerve, then join the vagus, distributed via the pharyngeal branches of vagus.

  8. Epithelial rotation is preceded by planar symmetry breaking of actomyosin and protects epithelial tissue from cell deformations.

    Science.gov (United States)

    Viktorinová, Ivana; Henry, Ian; Tomancak, Pavel

    2017-11-01

    Symmetry breaking is involved in many developmental processes that form bodies and organs. One of them is the epithelial rotation of developing tubular and acinar organs. However, how epithelial cells move, how they break symmetry to define their common direction, and what function rotational epithelial motions have remains elusive. Here, we identify a dynamic actomyosin network that breaks symmetry at the basal surface of the Drosophila follicle epithelium of acinar-like primitive organs, called egg chambers, and may represent a candidate force-generation mechanism that underlies the unidirectional motion of this epithelial tissue. We provide evidence that the atypical cadherin Fat2, a key planar cell polarity regulator in Drosophila oogenesis, directs and orchestrates transmission of the intracellular actomyosin asymmetry cue onto a tissue plane in order to break planar actomyosin symmetry, facilitate epithelial rotation in the opposite direction, and direct the elongation of follicle cells. In contrast, loss of this rotational motion results in anisotropic non-muscle Myosin II pulses that are disorganized in plane and causes cell deformations in the epithelial tissue of Drosophila eggs. Our work demonstrates that atypical cadherins play an important role in the control of symmetry breaking of cellular mechanics in order to facilitate tissue motion and model epithelial tissue. We propose that their functions may be evolutionarily conserved in tubular/acinar vertebrate organs.

  9. Using organotypic (raft) epithelial tissue cultures for the biosynthesis and isolation of infectious human papillomaviruses.

    Science.gov (United States)

    Ozbun, Michelle A; Patterson, Nicole A

    2014-08-01

    Papillomaviruses have a strict tropism for epithelial cells, and they are fully reliant on cellular differentiation for completion of their life cycles, resulting in the production of progeny virions. Thus, a permissive environment for full viral replication in vitro-wherein virion morphogenesis occurs under cooperative viral and cellular cues-requires the cultivation of epithelium. Presented in the first section of this unit is a protocol to grow differentiating epithelial tissues that mimic many important morphological and biochemical aspects of normal skin. The technique involves growing epidermal cells atop a dermal equivalent consisting of live fibroblasts and a collagen lattice. Epithelial stratification and differentiation ensues when the keratinocyte-dermal equivalent is placed at the air-liquid interface. The apparent floating nature of the cell-matrix in this method led to the nickname "raft" cultures. The general technique can be applied to normal low passage keratinocytes, to cells stably transfected with papillomavirus genes or genomes, or keratinocytes established from neoplastic lesions. However, infectious papillomavirus particles have only been isolated from organotypic epithelial cultures initiated with cells that maintain oncogenic human papillomavirus genomes in an extrachomosomal replicative form. The second section of this unit is dedicated to a virion isolation method that minimizes aerosol and skin exposure to these human carcinogens. Although the focus of the protocols is on the growth of tissues that yields infectious papillomavirus progeny, this culture system facilitates the investigation of these fastidious viruses during their complex replicative cycles, and raft tissues can be manipulated and harvested at any point during the process. Importantly, a single-step virus growth cycle is achieved in this process, as it is unlikely that progeny virions are released to initiate subsequent rounds of infection. Copyright © 2014 John Wiley

  10. Epithelial hyperplasia in human polycystic kidney diseases. Its role in pathogenesis and risk of neoplasia.

    OpenAIRE

    Bernstein, J.; Evan, A. P.; Gardner, K. D.

    1987-01-01

    The importance of tubular epithelial hyperplasia in polycystic kidney diseases has become apparent during the last decade. Micropapillary hyperplasia occurs in autosomal dominant polycystic kidney disease, in localized cystic disease, and in acquired cystic disease. Neoplastic or severely dysplastic epithelial hyperplasia occurs in von Hippel-Lindau disease. A histopathologically distinctive epithelial hyperplasia occurs in tuberous sclerosis. In each of these conditions, epithelial hyperplas...

  11. General Editorial

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. General Editorial. Articles in Resonance – Journal of Science Education. Volume 19 Issue 1 January 2014 pp 1-2 General Editorial. General Editorial on Publication Ethics · R Ramaswamy · More Details Fulltext PDF. Volume 19 Issue 1 January 2014 pp 3-3 ...

  12. Sodium selectivity of Reissner's membrane epithelial cells

    Directory of Open Access Journals (Sweden)

    Kim Kyunghee X

    2011-02-01

    Full Text Available Abstract Background Sodium absorption by Reissner's membrane is thought to contribute to the homeostasis of the volume of cochlear endolymph. It was previously shown that the absorptive transepithelial current was blocked by amiloride and benzamil. The most commonly-observed target of these drugs is the epithelial sodium channel (ENaC, which is composed of the three subunits α-,β- and γ-ENaC. However, other less-selective cation channels have also been observed to be sensitive to benzamil and amiloride. The aim of this study was to determine whether Reissner's membrane epithelial cells could support parasensory K+ absorption via amiloride- and benzamil-sensitive electrogenic pathways. Results We determined the molecular and functional expression of candidate cation channels with gene array (GEO GSE6196, RT-PCR, and whole-cell patch clamp. Transcript expression analysis of Reissner's membrane detected no amiloride-sensitive acid-sensing ion channels (ASIC1a, ASIC2a, ASIC2b nor amiloride-sensitive cyclic-nucleotide gated channels (CNGA1, CNGA2, CNGA4, CNGB3. By contrast, α-,β- and γ-ENaC were all previously reported as present in Reissner's membrane. The selectivity of the benzamil-sensitive cation currents was observed in whole-cell patch clamp recordings under Cl--free conditions where cations were the only permeant species. The currents were carried by Na+ but not K+, and the permeability of Li+ was greater than that of Na+ in Reissner's membrane. Complete replacement of bath Na+ with the inpermeable cation NMDG+ led to the same inward current as with benzamil in a Na+ bath. Conclusions These results are consistent with the amiloride/benzamil-sensitive absorptive flux of Reissner's membrane mediated by a highly Na+-selective channel that has several key characteristics in common with αβγ-ENaC. The amiloride-sensitive pathway therefore absorbs only Na+ in this epithelium and does not provide a parasensory K+ efflux route from scala

  13. Emergent material properties of developing epithelial tissues.

    Science.gov (United States)

    Machado, Pedro F; Duque, Julia; Étienne, Jocelyn; Martinez-Arias, Alfonso; Blanchard, Guy B; Gorfinkiel, Nicole

    2015-11-23

    Force generation and the material properties of cells and tissues are central to morphogenesis but remain difficult to measure in vivo. Insight is often limited to the ratios of mechanical properties obtained through disruptive manipulation, and the appropriate models relating stress and strain are unknown. The Drosophila amnioserosa epithelium progressively contracts over 3 hours of dorsal closure, during which cell apices exhibit area fluctuations driven by medial myosin pulses with periods of 1.5-6 min. Linking these two timescales and understanding how pulsatile contractions drive morphogenetic movements is an urgent challenge. We present a novel framework to measure in a continuous manner the mechanical properties of epithelial cells in the natural context of a tissue undergoing morphogenesis. We show that the relationship between apicomedial myosin fluorescence intensity and strain during fluctuations is consistent with a linear behaviour, although with a lag. We thus used myosin fluorescence intensity as a proxy for active force generation and treated cells as natural experiments of mechanical response under cyclic loading, revealing unambiguous mechanical properties from the hysteresis loop relating stress to strain. Amnioserosa cells can be described as a contractile viscoelastic fluid. We show that their emergent mechanical behaviour can be described by a linear viscoelastic rheology at timescales relevant for tissue morphogenesis. For the first time, we establish relative changes in separate effective mechanical properties in vivo. Over the course of dorsal closure, the tissue solidifies and effective stiffness doubles as net contraction of the tissue commences. Combining our findings with those from previous laser ablation experiments, we show that both apicomedial and junctional stress also increase over time, with the relative increase in apicomedial stress approximately twice that of other obtained measures. Our results show that in an epithelial

  14. Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients.

    Science.gov (United States)

    Sugita, Kazunari; Steer, Catherine A; Martinez-Gonzalez, Itziar; Altunbulakli, Can; Morita, Hideaki; Castro-Giner, Francesc; Kubo, Terufumi; Wawrzyniak, Paulina; Rückert, Beate; Sudo, Katsuko; Nakae, Susumu; Matsumoto, Kenji; O'Mahony, Liam; Akdis, Mübeccel; Takei, Fumio; Akdis, Cezmi A

    2018-01-01

    Bronchial epithelial barrier leakiness and type 2 innate lymphoid cells (ILC2s) have been separately linked to asthma pathogenesis; however, the influence of ILC2s on the bronchial epithelial barrier has not been investigated previously. We investigated the role of ILC2s in the regulation of bronchial epithelial tight junctions (TJs) and barrier function both in bronchial epithelial cells of asthmatic patients and healthy subjects and general innate lymphoid cell- and ILC2-deficient mice. Cocultures of human ILC2s and bronchial epithelial cells were used to determine transepithelial electrical resistance, paracellular flux, and TJ mRNA and protein expressions. The effect of ILC2s on TJs was examined by using a murine model of IL-33-induced airway inflammation in wild-type, recombination-activating gene 2 (Rag2) -/- , Rag2 -/- Il2rg -/- , and Rora sg/sg mice undergoing bone marrow transplantation to analyze the in vivo relevance of barrier disruption by ILC2s. ILC2s significantly impaired the epithelial barrier, as demonstrated by reduced transepithelial electrical resistance and increased fluorescein isothiocyanate-dextran permeability in air-liquid interface cultures of human bronchial epithelial cells. This was in parallel to decreased mRNAs and disrupted protein expression of TJ proteins and was restored by neutralization of IL-13. Intranasal administration of recombinant IL-33 to wild-type and Rag2 -/- mice lacking T and B cells triggered TJ disruption, whereas Rag2 -/- Il2rg -/- and Rora sg/sg mice undergoing bone marrow transplantation that lack ILC2s did not show any barrier leakiness. Direct nasal administration of IL-13 was sufficient to induce deficiency in the TJ barrier in the bronchial epithelium of mice in vivo. These data highlight an essential mechanism in asthma pathogenesis by demonstrating that ILC2s are responsible for bronchial epithelial TJ barrier leakiness through IL-13. Copyright © 2017 American Academy of Allergy, Asthma & Immunology

  15. MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS

    Science.gov (United States)

    MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS Epidemiological studies have shown a positive association between chronic exposure to chlorinated drinking water and human cancer, particularly of the urinary bladder. MX (3- chloro-4-(dichloromethyl)-5-hydrox...

  16. Human papillomavirus: cause of epithelial lacrimal sac neoplasia?

    DEFF Research Database (Denmark)

    Sjö, Nicolai Christian; von Buchwald, Christian; Cassonnet, Patricia

    2007-01-01

    PURPOSE: Epithelial tumours of the lacrimal sac are rare but important entities that may carry grave prognoses. In this study the prevalence and possible role of human papillomavirus (HPV) infection in epithelial tumours of the lacrimal sac were evaluated. METHODS: Five papillomas and six...... 11 RNA was demonstrated in two papillomas. CONCLUSIONS: By analysing 11 epithelial lacrimal sac papillomas and carcinomas using PCR, DNA ISH and RNA ISH, we found HPV DNA in all investigated transitional epithelium tumours of the lacrimal sac. HPV RNA was present in two of eight epithelial lacrimal...... sac tumours positive for HPV DNA. As RNA degrades fast in paraffin-embedded tissue, only a small fraction of DNA-positive tumours can be expected to be RNA-positive. We therefore suggest that HPV infection is associated with the development of lacrimal sac papillomas and carcinomas....

  17. Cell volume regulation in epithelial physiology and cancer

    DEFF Research Database (Denmark)

    Pedersen, Stine Helene Falsig; Hoffmann, Else Kay; Novak, Ivana

    2013-01-01

    expression of ion transporters and channels is now recognized as one of the hallmarks of cancer, it is timely to consider this especially for epithelia. Epithelial cells are highly proliferative and epithelial cancers, carcinomas, account for about 90% of all cancers. In this review we will focus on ion...... such as cancer, transepithelial and cell volume regulatory ion transport are dys-regulated. Furthermore, epithelial architecture and coordinated ion transport function are lost, cell survival/death balance is altered, and new interactions with the stroma arise, all contributing to drug resistance. Since altered...... transporters and channels with key physiological functions in epithelia and known roles in the development of cancer in these tissues. Their roles in cell survival, cell cycle progression, and development of drug resistance in epithelial cancers will be discussed....

  18. Risk factors of epithelial ovarian carcinomas among women with endometriosis

    DEFF Research Database (Denmark)

    Thomsen, Line H.; Schnack, Tine H.; Buchardi, Kristina

    2017-01-01

    INTRODUCTION: To evaluate the published literature on epidemiologic risk factors for epithelial ovarian cancer among women with a diagnosis of endometriosis. MATERIAL AND METHODS: A systematic literature search was conducted in PubMed and Scopus. Studies comparing epidemiologic risk factors...... an elevated risk of epithelial ovarian cancer. However, due to the limited number and size of studies in this area we cannot draw definitive conclusions. Further research into a risk factor profile among women with endometriosis is needed before clear recommendations can be made....... of epithelial ovarian cancer among women with endometriosis were included. A quality assessment was conducted using the Newcastle-Ottawa Scale. RESULTS: Eight of 794 articles met the inclusion criteria. A lower risk of epithelial ovarian cancer was observed in women with documented complete surgical excision...

  19. Cellular Plasticity of Epithelial Cells-Cause of Metastasis

    National Research Council Canada - National Science Library

    Sukumar, Saraswati

    2005-01-01

    .... We present a novel concept that cancer epithelial cells, possibly of stem cell origin, have inherent cellular plasticity and can differentiate into endothelial cells and form microvessels that serve...

  20. Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk.

    Science.gov (United States)

    Amankwah, Ernest K; Lin, Hui-Yi; Tyrer, Jonathan P; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bunker, Clareann H; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chen, Zhihua; Chen, Y Ann; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F; Eccles, Diana M; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goodman, Marc T; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis N; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Claus K; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Jim, Heather; Kellar, Melissa; Kiemeney, Lambertus A; Krakstad, Camilla; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Ian; Menon, Usha; Milne, Roger L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Pike, Malcolm C; Poole, Elizabeth M; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Thomsen, Lotte; Tangen, Ingvild L; Tworoger, Shelley S; van Altena, Anne M; Vierkant, Robert A; Vergote, Ignace; Walsh, Christine S; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Wu, Anna H; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Kelemen, Linda E; Berchuck, Andrew; Schildkraut, Joellen M; Ramus, Susan J; Goode, Ellen L; Monteiro, Alvaro N A; Gayther, Simon A; Narod, Steven A; Pharoah, Paul D P; Sellers, Thomas A; Phelan, Catherine M

    2015-12-01

    Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC. © 2015 WILEY PERIODICALS, INC.

  1. Molecular Characterization of Gastric Epithelial Cells Using Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Kevin A. Bockerstett

    2018-04-01

    Full Text Available The ability to analyze individual epithelial cells in the gastric mucosa would provide important insight into gastric disease, including chronic gastritis and progression to gastric cancer. However, the successful isolation of viable gastric epithelial cells (parietal cells, neck cells, chief cells, and foveolar cells from gastric glands has been limited due to difficulties in tissue processing. Furthermore, analysis and interpretation of gastric epithelial cell flow cytometry data has been difficult due to the varying sizes and light scatter properties of the different epithelial cells, high levels of autofluorescence, and poor cell viability. These studies were designed to develop a reliable method for isolating viable single cells from the corpus of stomachs and to optimize analyses examining epithelial cells from healthy and diseased stomach tissue by flow cytometry. We performed a two stage enzymatic digestion in which collagenase released individual gastric glands from the stromal tissue of the corpus, followed by a Dispase II digestion that dispersed these glands into greater than 1 × 106 viable single cells per gastric corpus. Single cell suspensions were comprised of all major cell lineages found in the normal gastric glands. A method describing light scatter, size exclusion, doublet discrimination, viability staining, and fluorescently-conjugated antibodies and lectins was used to analyze individual epithelial cells and immune cells. This technique was capable of identifying parietal cells and revealed that gastric epithelial cells in the chronically inflamed mucosa significantly upregulated major histocompatibility complexes (MHC I and II but not CD80 or CD86, which are costimulatory molecules involved in T cell activation. These studies describe a method for isolating viable single cells and a detailed description of flow cytometric analysis of cells from healthy and diseased stomachs. These studies begin to identify effects of

  2. Matriptase zymogen supports epithelial development, homeostasis and regeneration

    DEFF Research Database (Denmark)

    Friis, Stine; Tadeo, Daniel; Le-Gall, Sylvain M.

    2017-01-01

    Background Matriptase is a membrane serine protease essential for epithelial development, homeostasis, and regeneration, as well as a central orchestrator of pathogenic pericellular signaling in the context of inflammatory and proliferative diseases. Matriptase is an unusual protease in that its...... previously reported for transgenic mice mis-expressing wildtype epidermal matriptase. Equally surprising, mice engineered to express only zymogen-locked endogenous matriptase, unlike matriptase null mice, were viable, developed epithelial barrier function, and regenerated the injured epithelium. Compatible...

  3. Role of salivary epithelial toll-like receptors 2 and 4 in modulating innate immune responses in chronic periodontitis.

    Science.gov (United States)

    Swaminathan, V; Prakasam, S; Puri, V; Srinivasan, M

    2013-12-01

    Chronic periodontitis is initiated by sequential colonization with a broad array of bacteria and is perpetuated by an immune-inflammatory response to the changing biofilm. Host recognition of microbes is largely mediated by toll-like receptors (TLRs), which interact with conserved pathogen-associated molecular patterns. Based on ligand recognition, TLR-2 and TLR-4 interact with most periodontal pathogens. Extracrevicular bacterial reservoirs, such as the oral epithelial cells, contribute to the persistence of periodontitis. Human saliva is a rich source of oral epithelial cells that express functional TLRs. In this study we investigated the role of salivary epithelial cell (SEC) TLR-2 and TLR-4 in patients with generalized chronic periodontitis. Unstimulated whole saliva (UWS) was collected from patients with generalized chronic periodontitis and from healthy individuals after obtaining informed consent. Epithelial cells isolated from each UWS sample were assessed for TLR-2, TLR-4, peptidoglycan recognition protein (PGRP)-3 and PGRP-4 by quantitative real-time PCR. In addition, the SECs were stimulated in vitro with microbial products for up to 24 h. The culture supernatant was assessed for cytokines by ELISA. Stimulation with TLR-2- or TLR-4-specific ligands induced cytokine secretion with differential kinetics and up-regulated TLR2 and TLR4 mRNAs, respectively, in cultures of SECs from patients with periodontitis. In addition, the SECs from patients with periodontitis exhibited reduced PGRP3 and PGRP4 mRNAs, the TLR-responsive genes with antibacterial properties. SECs derived from the UWS of patients with chronic periodontitis are phenotypically distinct and could represent potential resources for assessing the epithelial responses to periodontal pathogens in the course of disease progression and persistence. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Malignant epithelial tumours of the parotid gland

    International Nuclear Information System (INIS)

    Langezaal, O.A.M.

    1982-01-01

    By means of the present clinico-pathologic study the author has attempted, through analysis of the evolution in a group of 101 patients suffering from malignant epithelial tumors of the parotis, to obtain insight into the clinical and pathologic factors governing the prognosis. Furthermore it was tried to assess the value of the different modes of therapy, including radiotherapy. Starting from certain types of tumors defined according to the WHO classification of tumors of the salivary glands, chapter 2 presents the reports in the literature on the pathology, clinical description and prognosis of the individual types of tumors. The initial treatment of the tumors is analysed with the use of a number of factors discussed in chapter 3. The significance of tumor-associated factors ascertained by the clinician and the pathologist as well as of patient-associated factors is correlated with the tumor-free period; the treatment-associated factors are correlated with the period of time between therapy and the advent of a local recurrence. The tumor-free period, instead of the survival time, was chosen as a criterion because the survival time depends not only on the prognostic factors but also on collateral circumstances, such as different diseases and the effect of the treatment instituted for the local recurrence. (Auth.)

  5. Conservative management of epithelial ovarian cancer.

    Science.gov (United States)

    Dexeus, S; Labastida, R; Dexeus, D

    2005-01-01

    We are currently faced with a progressive delay in the age at which women conceive for the first time. This raises the possibility of the appearance of gynecologic disorders that may affect fertility, including neoplasms of the ovary. Fertility-sparing surgery is defined as the preservation of ovarian tissue in one or both adnexa and/or the uterus. Borderline ovarian tumor should be treated with conservative surgery. Salpingo-oophorectomy, or even ovarian cystectomy, are the procedures of choice, with recurrence rates of 2-3% and up to 20% if a simple cystectomy is performed. Cystectomy is indicated in patients with bilateral borderline tumors or in patients with a residual ovary. Borderline tumors with invasive peritoneal implants behave as an invasive cancer in 10-30% of cases with a survival rate of 10-66% compared with 100% in borderline tumors without invasive implants. Prophylactic oophorectomy is recommended when desire of conception has been accomplished. Conservative surgery in invasive epithelial ovarian cancer is limited to Stage IA, grade 1 tumor, and in some highly selected grade 2 tumors of serous, mucinous or endometrioid type, well-encapsulated and free of adhesions. The standard oncological surgical procedure with preservation of the uterus and normal appearing ovary is recommended. This includes salpingo-oophorectomy, excision of any suspicious peritoneal lesion, multiple peritoneal biopsies, appendectomy (particularly in mucinous tumors), and pelvic and paraaortic lymphadenectomy.

  6. Retinal pigment epithelial dystrophy in Briard dogs.

    Science.gov (United States)

    Lightfoot, R M; Cabral, L; Gooch, L; Bedford, P G; Boulton, M E

    1996-01-01

    The eyes of normal Briard dogs, Briards affected with inherited retinal pigment epithelial dystrophy (RPED) and a range of normal crossbred and beagle dogs were examined and the histopathology of RPED in the Briard was compared with the histopathological features of ageing in the normal canine retina. RPED was characterised by the accumulation of auto-fluorescent lipofuscin-like inclusions in the retinal pigment epithelium (RPE), which initially involved only non-pigmented RPE cells overlying the tapetum but subsequently spread to all pigmented RPE cells. Secondary neuro-retinal degeneration was characterised by a gradual loss of the outer nuclear layer and the subsequent atrophy and degeneration of the inner retina. The loss of primary photoreceptors in the peripheral retina was accompanied by the migration of photoreceptor nuclei and appeared to resemble severe changes due to ageing. Intra-vitreal radiolabelled leucine was used to examine the rate of turnover of the outer segments of the rods in some Briards, but no significant variations were found. The activity of acid phosphatase in RPE was assayed in vitro and showed comparable regional variations in Briard and crossbred dogs. The results suggest that RPED in the Briard is unlikely to be due either to an increased rate of turnover of rod outer segments (and thus an increased phagocytic load) or to a primary insufficiency of lysosomal enzyme.

  7. Epithelial trafficking of Sonic hedgehog by megalin.

    Science.gov (United States)

    Morales, Carlos R; Zeng, Jibin; El Alfy, Mohamed; Barth, Jeremy L; Chintalapudi, Mastan Rao; McCarthy, Robert A; Incardona, John P; Argraves, W Scott

    2006-10-01

    We present here evidence of in vivo epithelial endocytosis and trafficking of non-lipid-modified Sonic hedgehog (ShhN) when infused into rat efferent ducts via microinjection. Initially, exogenous ShhN is detected in endocytic vesicles and early endosomes located near the apical plasma membrane of non-ciliated cells. Within 30-60 min following infusion, ShhN can be detected in lysosomes and at basolateral regions of non-ciliated cells. Basolaterally, ShhN was observed along the extracellular surfaces of interdigitated plasma membranes of adjacent cells and in the extracellular compartment underlying the efferent duct epithelium. Uptake and subcellular trafficking of infused ShhN by non-ciliated cells could be blocked by either anti-megalin IgG or the megalin antagonist, RAP. Ciliated cells, which do not express megalin, displayed little if any apical internalization of ShhN even though they were found to express Patched-1. However, ShhN was found in coated pits of lateral plasma membranes of ciliated cells as well as in underlying endocytic vesicles. We conclude that megalin-mediated endocytosis of ShhN can occur in megalin-expressing epithelia in vivo, and that the internalized ShhN can be targeted to the lysosome or transcytosed in the plane of the epithelium or across the epithelium. These findings highlight the multiple mechanisms by which megalin may influence Shh morphogen gradients in vivo.

  8. Lactobacillus Decelerates Cervical Epithelial Cell Cycle Progression

    Science.gov (United States)

    Vielfort, Katarina; Weyler, Linda; Söderholm, Niklas; Engelbrecht, Mattias; Löfmark, Sonja; Aro, Helena

    2013-01-01

    We investigated cell cycle progression in epithelial cervical ME-180 cells during colonization of three different Lactobacillus species utilizing live cell microscopy, bromodeoxyuridine incorporation assays, and flow cytometry. The colonization of these ME-180 cells by L. rhamnosus and L. reuteri, originating from human gastric epithelia and saliva, respectively, was shown to reduce cell cycle progression and to cause host cells to accumulate in the G1 phase of the cell cycle. The G1 phase accumulation in L. rhamnosus-colonized cells was accompanied by the up-regulation and nuclear accumulation of p21. By contrast, the vaginal isolate L. crispatus did not affect cell cycle progression. Furthermore, both the supernatants from the lactic acid-producing L. rhamnosus colonies and lactic acid added to cell culture media were able to reduce the proliferation of ME-180 cells. In this study, we reveal the diversity of the Lactobacillus species to affect host cell cycle progression and demonstrate that L. rhamnosus and L. reuteri exert anti-proliferative effects on human cervical carcinoma cells. PMID:23675492

  9. Lactobacillus decelerates cervical epithelial cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Katarina Vielfort

    Full Text Available We investigated cell cycle progression in epithelial cervical ME-180 cells during colonization of three different Lactobacillus species utilizing live cell microscopy, bromodeoxyuridine incorporation assays, and flow cytometry. The colonization of these ME-180 cells by L. rhamnosus and L. reuteri, originating from human gastric epithelia and saliva, respectively, was shown to reduce cell cycle progression and to cause host cells to accumulate in the G1 phase of the cell cycle. The G1 phase accumulation in L. rhamnosus-colonized cells was accompanied by the up-regulation and nuclear accumulation of p21. By contrast, the vaginal isolate L. crispatus did not affect cell cycle progression. Furthermore, both the supernatants from the lactic acid-producing L. rhamnosus colonies and lactic acid added to cell culture media were able to reduce the proliferation of ME-180 cells. In this study, we reveal the diversity of the Lactobacillus species to affect host cell cycle progression and demonstrate that L. rhamnosus and L. reuteri exert anti-proliferative effects on human cervical carcinoma cells.

  10. Haemophilia, AIDS and lung epithelial permeability

    Energy Technology Data Exchange (ETDEWEB)

    O' Doherty, M.J.; Page, C.J.; Harrington, C.; Nunan, T.; Savidge, G. (Haemophilia Centre and Coagulation Research Unit, Department of Nuclear Medicine, Rayne Institute, St. Thomas' Hospital, London (United Kingdom))

    1990-01-01

    Lung {sup 99m}Tc DTPA transfer was measured in HIV antibodypositive haemophiliacs (11 smokers, 26 nonsmokers, 5 patients with Pneumocystis carinii pneumonia (PCP)). Lung {sup 99m}Tc DTPA transfer as a marker of lung epithelial permeability was measured as the half time of transfer (from airspace into blood). This half time was faster in smokers compred to nonsmokers and the transfer curve was monoexponential. In nonsmokers no difference was observed between asymptomatic HIV-positive haemophiliacs and normal subjects, with the exception of the lung bases. At the lung basis in HIV-positive haemophiliac nonsmokers the transfer was faster than in normal individuals, implying increased alveolar permeability. Pneumocystis carinii pneumonia resulted in a rapid transfer of {sup 99m}Tc DTPA (mean T50 of 2 minutes) and the transfer curve was biphasic, confirming previous observations in homosexual HIV antibody-positive patients with PCP. These changes returned to a monoexponential profile by 6 weeks following successful treatment. The DTPA lung transfer study may enable clinicians to instigate therapy for PCP without the need for initial bronchoscopy and provide a noninvasive method for the reassessment of patients should further respiratory signs or symptoms develop. This method is considered to be highly cost-effective in that it obviates the use of factor VIII concentrates required to cover bronchoscopic procedures and, with its early application and ease of use as a follow-up investigation, permits the evaluation of patients on an outpatient basis, thus reducing hospital costs. (au).

  11. Haemophilia, AIDS and lung epithelial permeability

    International Nuclear Information System (INIS)

    O'Doherty, M.J.; Page, C.J.; Harrington, C.; Nunan, T.; Savidge, G.

    1990-01-01

    Lung 99m Tc DTPA transfer was measured in HIV antibodypositive haemophiliacs (11 smokers, 26 nonsmokers, 5 patients with Pneumocystis carinii pneumonia (PCP)). Lung 99m Tc DTPA transfer as a marker of lung epithelial permeability was measured as the half time of transfer (from airspace into blood). This half time was faster in smokers compred to nonsmokers and the transfer curve was monoexponential. In nonsmokers no difference was observed between asymptomatic HIV-positive haemophiliacs and normal subjects, with the exception of the lung bases. At the lung basis in HIV-positive haemophiliac nonsmokers the transfer was faster than in normal individuals, implying increased alveolar permeability. Pneumocystis carinii pneumonia resulted in a rapid transfer of 99m Tc DTPA (mean T50 of 2 minutes) and the transfer curve was biphasic, confirming previous observations in homosexual HIV antibody-positive patients with PCP. These changes returned to a monoexponential profile by 6 weeks following successful treatment. The DTPA lung transfer study may enable clinicians to instigate therapy for PCP without the need for initial bronchoscopy and provide a noninvasive method for the reassessment of patients should further respiratory signs or symptoms develop. This method is considered to be highly cost-effective in that it obviates the use of factor VIII concentrates required to cover bronchoscopic procedures and, with its early application and ease of use as a follow-up investigation, permits the evaluation of patients on an outpatient basis, thus reducing hospital costs. (au)

  12. Resveratrol inhibits transforming growth factor-β2-induced epithelial-to-mesenchymal transition in human retinal pigment epithelial cells by suppressing the Smad pathway

    Directory of Open Access Journals (Sweden)

    Chen CL

    2017-01-01

    Full Text Available Ching-Long Chen,1,2 Yi-Hao Chen,1,2 Ming-Cheng Tai,2 Chang-Min Liang,2 Da-Wen Lu,1,2 Jiann-Torng Chen1,2 1Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; 2Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Abstract: Proliferative vitreoretinopathy (PVR is the main cause of failure following retinal detachment surgery. Transforming growth factor (TGF-β2-induced epithelial-to-mesenchymal transition (EMT plays an important role in the development of PVR, and EMT inhibition decreases collagen gel contraction and fibrotic membrane formation, resulting in prevention of PVR. Resveratrol is naturally found in red wine and has inhibitory effects on EMT. Resveratrol is widely used in cardioprotection, neuroprotection, chemotherapy, and antiaging therapy. The purpose of this study was to investigate the effects of resveratrol on TGF-β2-induced EMT in ARPE-19 cells in vitro. We found that resveratrol suppressed the decrease of zona occludens-1 (ZO-1 and caused an increase of alpha-smooth muscle actin expression in TGF-β2-treated ARPE-19 cells, assessed using Western blots; moreover, it also suppressed the decrease in ZO-1 and the increase of vimentin expression, observed using immunocytochemistry. Resveratrol attenuated TGF-β2-induced wound closure and cell migration in ARPE-19 cells in a scratch wound test and modified Boyden chamber assay, respectively. We also found that resveratrol reduced collagen gel contraction – assessed by collagen matrix contraction assay – and suppressed the phosphorylation of Smad2 and Smad3 in TGF-β2-treated ARPE-19 cells. These results suggest that resveratrol mediates anti-EMT effects, which could be used in the prevention of PVR. Keywords: resveratrol, epithelial-to-mesenchymal transition, proliferative vitreoretinopathy, transforming growth factor-β2, retinal pigment epithelial cells

  13. Celiac Disease: Role of the Epithelial BarrierSummary

    Directory of Open Access Journals (Sweden)

    Michael Schumann

    2017-03-01

    Full Text Available In celiac disease (CD a T-cell–mediated response to gluten is mounted in genetically predisposed individuals, resulting in a malabsorptive enteropathy histologically highlighted by villous atrophy and crypt hyperplasia. Recent data point to the epithelial layer as an under-rated hot spot in celiac pathophysiology to date. This overview summarizes current functional and genetic evidence on the role of the epithelial barrier in CD, consisting of the cell membranes and the apical junctional complex comprising sealing as well as ion and water channel-forming tight junction proteins and the adherens junction. Moreover, the underlying mechanisms are discussed, including apoptosis of intestinal epithelial cells, biology of intestinal stem cells, alterations in the apical junctional complex, transcytotic uptake of gluten peptides, and possible implications of a defective epithelial polarity. Current research is directed toward new treatment options for CD that are alternatives or complementary therapeutics to a gluten-free diet. Thus, strategies to target an altered epithelial barrier therapeutically also are discussed. Keywords: Celiac Sprue, Gluten-Sensitive Enteropathy, Tight Junction, Epithelial Polarity, Partitioning-Defective Proteins, α-Gliadin 33mer

  14. Integrated Stress Response Mediates Epithelial Injury in Mechanical Ventilation.

    Science.gov (United States)

    Dolinay, Tamas; Himes, Blanca E; Shumyatcher, Maya; Lawrence, Gladys Gray; Margulies, Susan S

    2017-08-01

    Ventilator-induced lung injury (VILI) is a severe complication of mechanical ventilation that can lead to acute respiratory distress syndrome. VILI is characterized by damage to the epithelial barrier with subsequent pulmonary edema and profound hypoxia. Available lung-protective ventilator strategies offer only a modest benefit in preventing VILI because they cannot impede alveolar overdistension and concomitant epithelial barrier dysfunction in the inflamed lung regions. There are currently no effective biochemical therapies to mitigate injury to the alveolar epithelium. We hypothesize that alveolar stretch activates the integrated stress response (ISR) pathway and that the chemical inhibition of this pathway mitigates alveolar barrier disruption during stretch and mechanical ventilation. Using our established rat primary type I-like alveolar epithelial cell monolayer stretch model and in vivo rat mechanical ventilation that mimics the alveolar overdistension seen in acute respiratory distress syndrome, we studied epithelial responses to mechanical stress. Our studies revealed that the ISR signaling pathway is a key modulator of epithelial permeability. We show that prolonged epithelial stretch and injurious mechanical ventilation activate the ISR, leading to increased alveolar permeability, cell death, and proinflammatory signaling. Chemical inhibition of protein kinase RNA-like endoplasmic reticulum kinase, an upstream regulator of the pathway, resulted in decreased injury signaling and improved barrier function after prolonged cyclic stretch and injurious mechanical ventilation. Our results provide new evidence that therapeutic targeting of the ISR can mitigate VILI.

  15. Complex interactions between GSK3 and aPKC in Drosophila embryonic epithelial morphogenesis.

    Directory of Open Access Journals (Sweden)

    Nicole A Kaplan

    Full Text Available Generally, epithelial cells must organize in three dimensions to form functional tissue sheets. Here we investigate one such sheet, the Drosophila embryonic epidermis, and the morphogenetic processes organizing cells within it. We report that epidermal morphogenesis requires the proper distribution of the apical polarity determinant aPKC. Specifically, we find roles for the kinases GSK3 and aPKC in cellular alignment, asymmetric protein distribution, and adhesion during the development of this polarized tissue. Finally, we propose a model explaining how regulation of aPKC protein levels can reorganize both adhesion and the cytoskeleton.

  16. Epithelial Folding Driven by Apical or Basal-Lateral Modulation: Geometric Features, Mechanical Inference, and Boundary Effects.

    Science.gov (United States)

    Wen, Fu-Lai; Wang, Yu-Chiun; Shibata, Tatsuo

    2017-06-20

    During embryonic development, epithelial sheets fold into complex structures required for tissue and organ functions. Although substantial efforts have been devoted to identifying molecular mechanisms underlying epithelial folding, far less is understood about how forces deform individual cells to sculpt the overall sheet morphology. Here we describe a simple and general theoretical model for the autonomous folding of monolayered epithelial sheets. We show that active modulation of intracellular mechanics along the basal-lateral as well as the apical surfaces is capable of inducing fold formation in the absence of buckling instability. Apical modulation sculpts epithelia into shallow and V-shaped folds, whereas basal-lateral modulation generates deep and U-shaped folds. These characteristic tissue shapes remain unchanged when subject to mechanical perturbations from the surroundings, illustrating that the autonomous folding is robust against environmental variabilities. At the cellular scale, how cells change shape depends on their initial aspect ratios and the modulation mechanisms. Such cell deformation characteristics are verified via experimental measurements for a canonical folding process driven by apical modulation, indicating that our theory could be used to infer the underlying folding mechanisms based on experimental data. The mechanical principles revealed in our model could potentially guide future studies on epithelial folding in diverse systems. Copyright © 2017. Published by Elsevier Inc.

  17. Canine tracheal epithelial cells are more sensitive than rat tracheal epithelial cells to transforming growth factor beta induced growth inhibition

    International Nuclear Information System (INIS)

    Hubbs, A.F.; Hahn, F.F.; Kelly, G.; Thomassen, D.G.

    1988-01-01

    Transforming growth factor beta (TGFβ) markedly inhibited growth of canine tracheal epithelial (CTE) cells. Reduced responsiveness to TGFβ-induced growth inhibition accompanied neoplastic progression of these cells from primary to transformed to neoplastic. This was similar to the relationship between neoplastic progression and increased resistance to TGFβ-induced growth inhibition seen for rat tracheal epithelial (RTE) cells. The canine cells were more sensitive than rat cells to TGFβ-induced growth inhibition at all stages in the neoplastic process. (author)

  18. Generalized product

    OpenAIRE

    Greco, Salvatore; Mesiar, Radko; Rindone, Fabio

    2014-01-01

    Aggregation functions on [0,1] with annihilator 0 can be seen as a generalized product on [0,1]. We study the generalized product on the bipolar scale [–1,1], stressing the axiomatic point of view. Based on newly introduced bipolar properties, such as the bipolar increasingness, bipolar unit element, bipolar idempotent element, several kinds of generalized bipolar product are introduced and studied. A special stress is put on bipolar semicopulas, bipolar quasi-copulas and bipolar copulas.

  19. Double muscle innervation using end-to-side neurorrhaphy in rats Dupla inervação muscular com neurorrafia término-lateral em ratos

    Directory of Open Access Journals (Sweden)

    Elisangela Jeronymo Stipp-Brambilla

    2012-01-01

    Full Text Available CONTEXT AND OBJECTIVE: One of the techniques used for treating facial paralysis is double muscle innervation using end-to-end neurorrhaphy with sectioning of healthy nerves. The aim of this study was to evaluate whether double muscle innervation by means of end-to-side neurorrhaphy could occur, with maintenance of muscle innervation. DESIGN AND SETTING: Experimental study developed at the Experimental Research Center, Faculdade de Medicina de Botucatu, Unesp. METHODS: One hundred rats were allocated to five groups as follows: G1, control group; G2, the peroneal nerve was sectioned; G3, the tibial nerve was transected and the proximal stump was end-to-side sutured to the intact peroneal nerve; G4, 120 days after the G3 surgery, the peroneal nerve was sectioned proximally to the neurorrhaphy; G5, 120 days after the G3 surgery, the peroneal and tibial nerves were sectioned proximally to the neurorrhaphy. RESULTS: One hundred and fifty days after the surgery, G3 did not show any change in tibial muscle weight or muscle fiber diameter, but the axonal fiber diameter in the peroneal nerve distal to the neurorrhaphy had decreased. Although G4 showed atrophy of the cranial tibial muscle 30 days after sectioning the peroneal nerve, the electrophysiological test results and axonal diameter measurement confirmed that muscle reinnervation had occurred. CONCLUSION: These findings suggest that double muscle innervation did not occur through end-to-side neurorrhaphy; the tibial nerve was not able to maintain muscle innervation after the peroneal nerve had been sectioned, although muscle reinnervation was found to have occurred, 30 days after the peroneal nerve had been sectioned.CONTEXTO E OBJETIVO: Uma das técnicas utilizadas para tratamento da paralisia facial é a dupla inervação muscular com neurorrafia término-terminal, seccionando-se nervos sadios. O objetivo deste trabalho foi avaliar a ocorrência de dupla inervação muscular através de

  20. Cytomatrix synthesis in MDCK epithelial cells

    International Nuclear Information System (INIS)

    Mitchell, J.J.; Low, R.B.; Woodcock-Mitchell, J.L.

    1990-01-01

    Detailed information regarding the synthesis rates of individual protein components is important in understanding the assembly and dynamics of the cytoskeletal matrix of eukaryotic cells. As an approach to this topic, the dual isotope technique of Clark and Zak, was employed to measure fractional synthesis rates (FSRs) in growing and quiescent cultures of MDCK epithelial cells. Cell protein was labeled to equilibrium with [14C]leucine over several days and then pulse-labeled for 4 hours with [3H]leucine. FSRs (as percent per hour) were calculated from the 3H/14C ratio of cell extracts or individual proteins separated by two-dimensional polyacrylamide gel electrophoresis and the 3H/14C ratio of free leucine in the medium. Synthesis of total cell protein rose from approximately 1.4%/hour in quiescent cells to 3.5%/hour in the growing cultures. The latter rate was sufficient to account for the rate of protein accumulation and a low level of turnover in the growing cultures. The FSR of the buffered-Triton soluble extract was higher and the cytoskeletal FSR significantly lower than that for total protein in quiescent monolayers. This difference, however, was not observed in growing cultures. A distinct pattern of differences was seen in the FSRs of individual cytoskeletal proteins in the quiescent cultures. Vimentin synthesis was significantly lower than that of the keratins and the keratin FSRs were not obviously matched in pairwise fashion. Unexpectedly, the FSRs of alpha- and beta-tubulin diverged in quiescent cells with alpha-tubulin turnover exceeding beta-tubulin. Likewise, components of the microfilament lattice showed unequal fractional synthesis rates, myosin and alpha-actinin being faster than actin. In addition, the FSR for globular actin exceeded that of the cytoskeletal associated form

  1. Regulated Mucin Secretion from Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Kenneth Bruce Adler

    2013-09-01

    Full Text Available Secretory epithelial cells of the proximal airways synthesize and secrete gel-forming polymeric mucins. The secreted mucins adsorb water to form mucus that is propelled by neighboring ciliated cells, providing a mobile barrier which removes inhaled particles and pathogens from the lungs. Several features of the intracellular trafficking of mucins make the airway secretory cell an interesting comparator for the cell biology of regulated exocytosis. Polymeric mucins are exceedingly large molecules (up to 3x10^6 D per monomer whose folding and initial polymerization in the ER requires the protein disulfide isomerase Agr2. In the Golgi, mucins further polymerize to form chains and possibly branched networks comprising more than 20 monomers. The large size of mucin polymers imposes constraints on their packaging into transport vesicles along the secretory pathway. Sugar side chains account for >70% of the mass of mucins, and their attachment to the protein core by O-glycosylation occurs in the Golgi. Mature polymeric mucins are stored in large secretory granules ~1 um in diameter. These are translocated to the apical membrane to be positioned for exocytosis by cooperative interactions among MARCKS, cysteine string protein (CSP, HSP70 and the cytoskeleton. Mucin granules undergo exocytic fusion with the plasma membrane at a low basal rate and a high stimulated rate. Both rates are mediated by a regulated exocytic mechanism as indicated by phenotypes in both basal and stimulated secretion in mice lacking Munc13-2, a sensor of the second messengers calcium and diacylglycerol (DAG. Basal secretion is induced by low levels of activation of P2Y2 purinergic and A3 adenosine receptors by extracellular ATP released in paracrine fashion and its metabolite adenosine. Stimulated secretion is induced by high levels of the same ligands, and possibly by inflammatory mediators as well. Activated receptors are coupled to phospholipase C by Gq, resulting in the

  2. Pancreatic mesenchyme regulates epithelial organogenesis throughout development.

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    Limor Landsman

    2011-09-01

    Full Text Available The developing pancreatic epithelium gives rise to all endocrine and exocrine cells of the mature organ. During organogenesis, the epithelial cells receive essential signals from the overlying mesenchyme. Previous studies, focusing on ex vivo tissue explants or complete knockout mice, have identified an important role for the mesenchyme in regulating the expansion of progenitor cells in the early pancreas epithelium. However, due to the lack of genetic tools directing expression specifically to the mesenchyme, the potential roles of this supporting tissue in vivo, especially in guiding later stages of pancreas organogenesis, have not been elucidated. We employed transgenic tools and fetal surgical techniques to ablate mesenchyme via Cre-mediated mesenchymal expression of Diphtheria Toxin (DT at the onset of pancreas formation, and at later developmental stages via in utero injection of DT into transgenic mice expressing the Diphtheria Toxin receptor (DTR in this tissue. Our results demonstrate that mesenchymal cells regulate pancreatic growth and branching at both early and late developmental stages by supporting proliferation of precursors and differentiated cells, respectively. Interestingly, while cell differentiation was not affected, the expansion of both the endocrine and exocrine compartments was equally impaired. To further elucidate signals required for mesenchymal cell function, we eliminated β-catenin signaling and determined that it is a critical pathway in regulating mesenchyme survival and growth. Our study presents the first in vivo evidence that the embryonic mesenchyme provides critical signals to the epithelium throughout pancreas organogenesis. The findings are novel and relevant as they indicate a critical role for the mesenchyme during late expansion of endocrine and exocrine compartments. In addition, our results provide a molecular mechanism for mesenchymal expansion and survival by identifying β-catenin signaling as an

  3. Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Hirai, H.; Lochter, A.; Galosy, S.; Koshida, S.; Niwa, S.; Bissell, M.J.

    1997-10-13

    Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not anti-HGF antibodies. The branch length, however, was roughly proportional to the ability of the factors to induce growth. Accordingly, epimorphin-negative epithelial cells simply grew in a cluster in response to the growth factors and failed to branch. When recombinant epimorphin was added to these collagen gels, epimorphin-negative cells underwent branching morphogenesis. The mode of action of epimorphin on morphogenesis of the gland, however, was dependent on how it was presented to the mammary cells. If epimorphin was overexpressed in epimorphin-negative epithelial cells under regulation of an inducible promoter or was allowed to coat the surface of each epithelial cell in a nonpolar fashion, the cells formed globular, alveoli-like structures with a large central lumen instead of branching ducts. This process was enhanced also by addition of HGF, EGF, or other growth factors and was inhibited by epimorphin antibodies. These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized.

  4. Human Mammary Luminal Epithelial Cells Contain Progenitors to Myoepithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Pechoux, Christine; Gudjonsson, Thorarinn; Ronnov-Jessen, Lone; Bissell, Mina J; Petersen, Ole

    1999-02-01

    The origin of the epithelial and myoepithelial cells in the human breast has not been delineated. In this study we have addressed whether luminal epithelial cells and myoepithelial cells are vertically connected, i.e., whether one is the precursor for the other. We used a primary culture assay allowing preservation of basic phenotypic traits of luminal epithelial and myoepithelial cells in culture. The two cell types were then separated immunomagnetically using antibodies directed against lineage-specific cell surface antigens into at best 100% purity. The cellular identity was ascertained by cytochemistry, immunoblotting, and 2-D gel electrophoresis. Luminal epithelial cells were identified by strong expression of cytokeratins 18 and 19 while myoepithelial cells were recognized by expression of vimentin and {alpha}-smooth muscle actin. We used a previously devised culture medium (CDM4) that allows vigorous expansion of proliferative myoepithelial cells and also devised a medium (CDM6) that allowed sufficient expansion of differentiated luminal epithelial cells based on addition of hepatocyte growth factor/scatter factor. The two different culture media supported each lineage for at least five passages without signs of interconversion. We used parallel cultures where we switched culture media, thus testing the ability of each lineage to convert to the other. Whereas the myoepithelial lineage showed no signs of interconversion, a subset of luminal epithelial cells, gradually, but distinctly, converted to myoepithelial cells. We propose that in the mature human breast, it is the luminal epithelial cell compartment that gives rise to myoepithelial cells rather than the other way around.

  5. Probiotics promote endocytic allergen degradation in gut epithelial cells

    International Nuclear Information System (INIS)

    Song, Chun-Hua; Liu, Zhi-Qiang; Huang, Shelly; Zheng, Peng-Yuan; Yang, Ping-Chang

    2012-01-01

    Highlights: ► Knockdown of A20 compromised the epithelial barrier function. ► The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. ► Antigens transported across A20-deficient HT-29 monolayers conserved antigenicity. ► Probiotic proteins increased the expression of A20 in HT-29 cells. -- Abstract: Background and aims: Epithelial barrier dysfunction plays a critical role in the pathogenesis of allergic diseases; the mechanism is to be further understood. The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells. This study aims to elucidate the role of A20 in the maintenance of gut epithelial barrier function. Methods: Gut epithelial cell line, HT-29 cell, was cultured into monolayers to evaluate the barrier function in transwells. RNA interference was employed to knock down the A20 gene in HT-29 cells to test the role of A20 in the maintenance of epithelial barrier function. Probiotic derived proteins were extracted from the culture supernatants using to enhance the expression of A20 in HT-29 cells. Results: The results showed that the knockdown of A20 compromised the epithelial barrier function in HT-29 monolayers, mainly increased the intracellular permeability. The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Allergens collected from the transwell basal chambers of A20-deficient HT-29 monolayers still conserved functional antigenicity. Treating with probiotic derived proteins increased the expression of A20 in HT-29 cells and promote the barrier function. Conclusion: A20 plays an important role in the maintenance of epithelial barrier function as shown by HT-29 monolayer. Probiotic derived protein increases the expression of A20 and promote the HT-29 monolayer barrier function.

  6. Spontaneous regression of epithelial downgrowth from clear corneal phacoemulsification wound

    Directory of Open Access Journals (Sweden)

    Ryan M. Jaber

    2018-06-01

    Full Text Available Purpose: To report a case of spontaneous regression of optical coherence tomography (OCT and confocal microscopy-supported epithelial downgrowth associated with clear corneal phacoemulsification wound. Observations: A 66-year-old Caucasian male presented two years after phacoemulsification in the left eye with an enlarging cornea endothelial lesion in that eye. His early post-operative course had been complicated by corneal edema and iris transillumination defects. The patient presented to our clinic with a large geographic sheet of epithelial downgrowth and iris synechiae to the temporal clear corneal wound. His vision was correctable to 20/25 in his left eye. Anterior segment OCT showed a hyperreflective layer on the posterior cornea with an abrupt transition that corresponded to the clinical transition zone of the epithelial downgrowth. Confocal microscopy showed polygonal cells with hyperreflective nuclei suggestive of epithelial cells in the area of the lesion with a transition to a normal endothelial cell mosaic. Given the lack of glaucoma or inflammation and the relatively good vision, the plan was made to closely monitor for progression with the anticipation that he may require aggressive surgery. Over course of subsequent follow-up visits at three, seven and ten months; the endothelial lesion receded significantly. Confocal imaging in the area of the previously affected cornea showed essentially normal morphology with anan endothelial cell count of 1664 cells/mm2. Conclusions and importance: Epithelial downgrowth may spontaneously regress. Though the mechanism is yet understood, contact inhibition of movement may play a role. Despite this finding, epithelial downgrowth is typically a devastating process requiring aggressive treatment. Keywords: Epithelial downgrowth, Spontaneous regression, Confocal microscopy, Contact inhibition of movement

  7. Probiotics promote endocytic allergen degradation in gut epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Song, Chun-Hua [Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou (China); Liu, Zhi-Qiang [Department of Gastroenterology, The Second Hospital, Zhengzhou University, Zhengzhou (China); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada); Huang, Shelly [Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada); Zheng, Peng-Yuan, E-mail: medp7123@126.com [Department of Gastroenterology, The Second Hospital, Zhengzhou University, Zhengzhou (China); Yang, Ping-Chang, E-mail: yangp@mcmaster.ca [Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada)

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer Knockdown of A20 compromised the epithelial barrier function. Black-Right-Pointing-Pointer The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Black-Right-Pointing-Pointer Antigens transported across A20-deficient HT-29 monolayers conserved antigenicity. Black-Right-Pointing-Pointer Probiotic proteins increased the expression of A20 in HT-29 cells. -- Abstract: Background and aims: Epithelial barrier dysfunction plays a critical role in the pathogenesis of allergic diseases; the mechanism is to be further understood. The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells. This study aims to elucidate the role of A20 in the maintenance of gut epithelial barrier function. Methods: Gut epithelial cell line, HT-29 cell, was cultured into monolayers to evaluate the barrier function in transwells. RNA interference was employed to knock down the A20 gene in HT-29 cells to test the role of A20 in the maintenance of epithelial barrier function. Probiotic derived proteins were extracted from the culture supernatants using to enhance the expression of A20 in HT-29 cells. Results: The results showed that the knockdown of A20 compromised the epithelial barrier function in HT-29 monolayers, mainly increased the intracellular permeability. The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Allergens collected from the transwell basal chambers of A20-deficient HT-29 monolayers still conserved functional antigenicity. Treating with probiotic derived proteins increased the expression of A20 in HT-29 cells and promote the barrier function. Conclusion: A20 plays an important role in the maintenance of epithelial barrier function as shown by HT-29 monolayer. Probiotic derived protein increases the expression of A20 and promote the HT-29 monolayer barrier function.

  8. CYP1B1, Oxidative Stress, and Inflammation in the Etiology of Ovarian Epithelial Cancer Using an Avian Model of Ovarian Carcinoma

    Science.gov (United States)

    2007-11-01

    fibrovascular cores lined by atypical epithelial cells. Tumors 7 resembling human endometrioid carcinomas were generally characterized by a complex 8...presence of focal lesions, glandular structures, cells with pleomorphic nucleus with mitotic bodies and hyperplastic surface or stromal hyperplasia ...Non-tumor pathologies included increased atresia of developing stromal follicles, cystic structures, hyperplasia without any focal lesion or malignant

  9. Circulating 25-Hydroxyvitamin D and Risk of Epithelial Ovarian Cancer

    Science.gov (United States)

    Zheng, Wei; Danforth, Kim N.; Tworoger, Shelley S.; Goodman, Marc T.; Arslan, Alan A.; Patel, Alpa V.; McCullough, Marjorie L.; Weinstein, Stephanie J.; Kolonel, Laurence N.; Purdue, Mark P.; Shu, Xiao-Ou; Snyder, Kirk; Steplowski, Emily; Visvanathan, Kala; Yu, Kai; Zeleniuch-Jacquotte, Anne; Gao, Yu-Tang; Hankinson, Susan E.; Harvey, Chinonye; Hayes, Richard B.; Henderson, Brian E.; Horst, Ronald L.; Helzlsouer, Kathy J.

    2010-01-01

    A role for vitamin D in ovarian cancer etiology is supported by ecologic studies of sunlight exposure, experimental mechanism studies, and some studies of dietary vitamin D intake and genetic polymorphisms in the vitamin D receptor. However, few studies have examined the association of circulating 25-hydroxyvitamin D (25(OH)D), an integrated measure of vitamin D status, with ovarian cancer risk. A nested case-control study was conducted among 7 prospective studies to evaluate the circulating 25(OH)D concentration in relation to epithelial ovarian cancer risk. Logistic regression models were used to estimate odds ratios and 95% confidence intervals among 516 cases and 770 matched controls. Compared with 25(OH)D concentrations of 50–<75 nmol/L, no statistically significant associations were observed for <37.5 (odds ratio (OR) = 1.21, 95% confidence interval (CI): 0.87, 1.70), 37.5–<50 (OR = 1.03, 95% CI: 0.75, 1.41), or ≥75 (OR = 1.11, 95% CI: 0.79, 1.55) nmol/L. Analyses stratified by tumor subtype, age, body mass index, and other variables were generally null but suggested an inverse association between 25(OH)D and ovarian cancer risk among women with a body mass index of ≥25 kg/m2 (Pinteraction < 0.01). In conclusion, this large pooled analysis did not support an overall association between circulating 25(OH)D and ovarian cancer risk, except possibly among overweight women. PMID:20562186

  10. Tungsten-induced carcinogenesis in human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Laulicht, Freda; Brocato, Jason; Cartularo, Laura; Vaughan, Joshua; Wu, Feng; Kluz, Thomas; Sun, Hong [Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987 (United States); Oksuz, Betul Akgol [Genome Technology Center, New York University Langone Medical Center, New York, NY 10016 (United States); Shen, Steven [Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, NY 10016 (United States); Peana, Massimiliano; Medici, Serenella; Zoroddu, Maria Antonietta [Department of Chemistry and Pharmacy, University of Sassari, Sassari (Italy); Costa, Max, E-mail: Max.Costa@nyumc.org [Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987 (United States)

    2015-10-01

    Metals such as arsenic, cadmium, beryllium, and nickel are known human carcinogens; however, other transition metals, such as tungsten (W), remain relatively uninvestigated with regard to their potential carcinogenic activity. Tungsten production for industrial and military applications has almost doubled over the past decade and continues to increase. Here, for the first time, we demonstrate tungsten's ability to induce carcinogenic related endpoints including cell transformation, increased migration, xenograft growth in nude mice, and the activation of multiple cancer-related pathways in transformed clones as determined by RNA sequencing. Human bronchial epithelial cell line (Beas-2B) exposed to tungsten developed carcinogenic properties. In a soft agar assay, tungsten-treated cells formed more colonies than controls and the tungsten-transformed clones formed tumors in nude mice. RNA-sequencing data revealed that the tungsten-transformed clones altered the expression of many cancer-associated genes when compared to control clones. Genes involved in lung cancer, leukemia, and general cancer genes were deregulated by tungsten. Taken together, our data show the carcinogenic potential of tungsten. Further tests are needed, including in vivo and human studies, in order to validate tungsten as a carcinogen to humans. - Highlights: • Tungsten (W) induces cell transformation and increases migration in vitro. • W increases xenograft growth in nude mice. • W altered the expression of cancer-related genes such as those involved in leukemia. • Some of the dysregulated leukemia genes include, CD74, CTGF, MST4, and HOXB5. • For the first time, data is presented that demonstrates tungsten's carcinogenic potential.

  11. Herpes simplex virus internalization into epithelial cells requires Na+/H+ exchangers and p21-activated kinases but neither clathrin- nor caveolin-mediated endocytosis.

    Science.gov (United States)

    Devadas, Deepika; Koithan, Thalea; Diestel, Randi; Prank, Ute; Sodeik, Beate; Döhner, Katinka

    2014-11-01

    Herpes simplex virus 1 (HSV-1) is an alphaherpesvirus that has been reported to infect some epithelial cell types by fusion at the plasma membrane but others by endocytosis. To determine the molecular mechanisms of productive HSV-1 cell entry, we perturbed key endocytosis host factors using specific inhibitors, RNA interference (RNAi), or overexpression of dominant negative proteins and investigated their effects on HSV-1 infection in the permissive epithelial cell lines Vero, HeLa, HEp-2, and PtK2. HSV-1 internalization required neither endosomal acidification nor clathrin- or caveolin-mediated endocytosis. In contrast, HSV-1 gene expression and internalization were significantly reduced after treatment with 5-(N-ethyl-N-isopropyl)amiloride (EIPA). EIPA blocks the activity of Na(+)/H(+) exchangers, which are plasma membrane proteins implicated in all forms of macropinocytosis. HSV-1 internalization furthermore required the function of p21-activated kinases that contribute to macropinosome formation. However, in contrast to some forms of macropinocytosis, HSV-1 did not enlist the activities of protein kinase C (PKC), tyrosine kinases, C-terminal binding protein 1, or dynamin to activate its internalization. These data suggest that HSV-1 depends on Na(+)/H(+) exchangers and p21-activated kinases either for macropinocytosis or for local actin rearrangements required for fusion at the plasma membrane or subsequent passage through the actin cortex underneath the plasma membrane. After initial replication in epithelial cells, herpes simplex viruses (HSVs) establish latent infections in neurons innervating these regions. Upon primary infection and reactivation from latency, HSVs cause many human skin and neurological diseases, particularly in immunocompromised hosts, despite the availability of effective antiviral drugs. Many viruses use macropinocytosis for virus internalization, and many host factors mediating this entry route have been identified, although the

  12. General relativity

    International Nuclear Information System (INIS)

    Kenyon, I.R.

    1990-01-01

    General relativity is discussed in this book at a level appropriate to undergraduate students of physics and astronomy. It describes concepts and experimental results, and provides a succinct account of the formalism. A brief review of special relativity is followed by a discussion of the equivalence principle and its implications. Other topics covered include the concepts of curvature and the Schwarzschild metric, test of the general theory, black holes and their properties, gravitational radiation and methods for its detection, the impact of general relativity on cosmology, and the continuing search for a quantum theory of gravity. (author)

  13. Epithelial-Mesenchymal Transition in Tissue Repair and Fibrosis

    Science.gov (United States)

    Stone, Rivka C.; Pastar, Irena; Ojeh, Nkemcho; Chen, Vivien; Liu, Sophia; Garzon, Karen I.; Tomic-Canic, Marjana

    2016-01-01

    Epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics which confer migratory capacity. EMT and its converse, MET (mesenchymal-to-epithelial transition), are integral stages of many physiologic processes, and as such are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes - the resident skin epithelial cells - migrate across the wound bed to restore the epidermal barrier. Moreover, EMT also plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblast arises from cells of epithelial lineage in response to injury but is pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the impaired repair of fibrotic wounds may identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. PMID:27461257

  14. Lingual Epithelial Stem Cells and Organoid Culture of Them

    Directory of Open Access Journals (Sweden)

    Hiroko Hisha

    2016-01-01

    Full Text Available As tongue cancer is one of the major malignant cancers in the world, understanding the mechanism of maintenance of lingual epithelial tissue, which is known to be the origin of tongue cancer, is unquestionably important. However, the actual stem cells that are responsible for the long-term maintenance of the lingual epithelium have not been identified. Moreover, a simple and convenient culture method for lingual epithelial stem cells has not yet been established. Recently, we have shown that Bmi1-positive cells, residing at the second or third layer of the epithelial cell layer at the base of the interpapillary pit (IPP, were slow-cycling and could supply keratinized epithelial cells for over one year, indicating that Bmi1-positive cells are long-term lingual epithelial stem cells. In addition, we have developed a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Here, we discuss current progress in the identification of lingual stem cells and future applications of the lingual culture system for studying the regulatory mechanisms of the lingual epithelium and for regenerative medicine.

  15. Role of airway epithelial barrier dysfunction in pathogenesis of asthma.

    Science.gov (United States)

    Gon, Yasuhiro; Hashimoto, Shu

    2018-01-01

    Bronchial asthma is characterized by persistent cough, increased sputum, and repeated wheezing. The pathophysiology underlying these symptoms is the hyper-responsiveness of the airway along with chronic airway inflammation. Repeated injury, repair, and regeneration of the airway epithelium following exposure to environmental factors and inflammation results in histological changes and functional abnormalities in the airway mucosal epithelium; such changes are believed to have a significant association with the pathophysiology of asthma. Damage to the barrier functions of the airway epithelium enhances mucosal permeability of foreign substances in the airway epithelium of patients with asthma. Thus, epithelial barrier fragility is closely involved in releasing epithelial cytokines (e.g., TSLP, IL-25, and IL-33) because of the activation of airway epithelial cells, dendritic cells, and innate group 2 innate lymphoid cells (ILC2). Functional abnormalities of the airway epithelial cells along with the activation of dendritic cells, Th2 cells, and ILC2 form a single immunopathological unit that is considered to cause allergic airway inflammation. Here we use the latest published literature to discuss the potential pathological mechanisms regarding the onset and progressive severity of asthma with regard to the disruption of the airway epithelial function. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  16. DA-6034 Induces [Ca(2+)]i Increase in Epithelial Cells.

    Science.gov (United States)

    Yang, Yu-Mi; Park, Soonhong; Ji, Hyewon; Kim, Tae-Im; Kim, Eung Kweon; Kang, Kyung Koo; Shin, Dong Min

    2014-04-01

    DA-6034, a eupatilin derivative of flavonoid, has shown potent effects on the protection of gastric mucosa and induced the increases in fluid and glycoprotein secretion in human and rat corneal and conjunctival cells, suggesting that it might be considered as a drug for the treatment of dry eye. However, whether DA-6034 induces Ca(2+) signaling and its underlying mechanism in epithelial cells are not known. In the present study, we investigated the mechanism for actions of DA-6034 in Ca(2+) signaling pathways of the epithelial cells (conjunctival and corneal cells) from human donor eyes and mouse salivary gland epithelial cells. DA-6034 activated Ca(2+)-activated Cl(-) channels (CaCCs) and increased intracellular calcium concentrations ([Ca(2+)]i) in primary cultured human conjunctival cells. DA-6034 also increased [Ca(2+)]i in mouse salivary gland cells and human corneal epithelial cells. [Ca(2+)]i increase of DA-6034 was dependent on the Ca(2+) entry from extracellular and Ca(2+) release from internal Ca(2+) stores. Interestingly, these effects of DA-6034 were related to ryanodine receptors (RyRs) but not phospholipase C/inositol 1,4,5-triphosphate (IP3) pathway and lysosomal Ca(2+) stores. These results suggest that DA-6034 induces Ca(2+) signaling via extracellular Ca(2+) entry and RyRs-sensitive Ca(2+) release from internal Ca(2+) stores in epithelial cells.

  17. Epithelial-mesenchymal transition in tissue repair and fibrosis.

    Science.gov (United States)

    Stone, Rivka C; Pastar, Irena; Ojeh, Nkemcho; Chen, Vivien; Liu, Sophia; Garzon, Karen I; Tomic-Canic, Marjana

    2016-09-01

    The epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including the loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics that confer migratory capacity. EMT and its converse, MET (mesenchymal-epithelial transition), are integral stages of many physiologic processes and, as such, are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes (the resident skin epithelial cells) migrate across the wound bed to restore the epidermal barrier. Moreover, EMT plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblasts arise from cells of the epithelial lineage in response to injury but are pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the faulty repair of fibrotic wounds might identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. Graphical Abstract Model for injury-triggered EMT activation in physiologic wound repair (left) and fibrotic wound healing (right).

  18. Immunohistochemical Expression of MCM-2 in Oral Epithelial Dysplasias.

    Science.gov (United States)

    Zakaria, Samar H; Farag, Heba A; Khater, Dina S

    2016-03-17

    Oral cancer is one of the most frequent cancers in the world. It arises from epithelial dysplasia. Hence, identifying these lesions in an early stage could prevent their malignant transformation. The aim of the present work was to assess the cell proliferative activity of minichromosome maintenance protein (MCM-2) in oral epithelial dysplastic lesions and to correlate the results with different grades of epithelial dysplasia in an attempt to use MCM-2 in the early detection of malignancy. MCM-2 expression was determined by the nuclear count in a total of 30 oral epithelial dysplastic specimens roughly classified into 10 cases of mild, moderate, and severe dysplasia. Five cases of early invasive squamous-cell carcinomas and 5 cases of epithelial hyperplasia were also included. The MCM-2 immunostaining was found to increase gradually from mild to moderate to severe dysplasia and reached its maximum value in early invasive squamous cell carcinoma. MCM-2 is of prognostic value in cases of oral dysplasia that have a tendency to undergo malignant transformation.

  19. Rabbit uterine epithelial cells: Co-culture with spermatozoa

    International Nuclear Information System (INIS)

    Boice, M.L.

    1988-01-01

    A primary culture of rabbit uterine epithelial cells was established and their effects on sperm function were examined in vitro. Epithelial cells were isolated from uteri of estrous rabbits and cultured on floating collagen gels in phenol red-free medium supplemented with 5% fetal bovine serum. Light microscopy and keratin staining showed that the epithelial cell population established in culture had morphological characteristics similar to that seen in the intact endometrium. Cells were cultured with 3 H-leucine and uptake of label by cells and its incorporation into cellular and secretory proteins determined. When compared to cells cultured for 24-48 h, incorporation of label into cellular protein was lower at 72-96 h, but secretion increased. Estradiol 17-β did not affect label uptake or incorporation, but did enhance proliferation of cells as judged by total DNA content of the cell population. Analysis of proteins in media by sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography suggested that epithelial and stromal cells synthesis proteins that may be secretory in nature during 72-96 h culture. Twenty-nine to thirty-one h after initiation of epithelial cultures, 1-2 x 10 6 sperm were co-incubated with cells and sperm viability, motility, loss of acrosome and fertilizing ability determined

  20. Immunohistochemical study of epithelial-myofibroblast interaction in Barrett metaplasia

    Directory of Open Access Journals (Sweden)

    Ochicha O

    2010-04-01

    Full Text Available Context: Sub-epithelial myofibroblasts are known to influence the biology (proliferation, differentiation and apoptosis of overlying epithelia. In the intestine, myofibroblasts have been demonstrated to be essential for epithelial differentiation. It is therefore hypothesized that myofibroblasts may also be involved in intestinal metaplasia that is characteristic of Barrett esophagus. Objective: This study endeavors to immunohistologically evaluate epithelial-myofibroblast interaction in Barrett′s metaplasia. Materials and Methods: Nineteen archival esophageal endoscopic biopsies of Barrett′s metaplasia were immune-phenotyped for the following epithelial and myofibroblast antigens - cytokeratins (CK 8, 13, 18, CDX2 (Caudal type homeobox 2, a-smooth muscle actin (SMA. Results: α-SMA immunostaining revealed close association between myofibroblasts and metaplastic Barrett′s epithelium but not with normal esophageal squamous epithelium. Myofibroblasts were more prominent in dysplastic than in non-dysplastic Barrett metaplasia. CDX2 and CK 8/18, indicators of intestinal differentiation were expressed in Barrett metaplasia but not normal esophageal squamous epithelium, while the reverse was the case for CK 13, which only stained normal esophageal squamous epithelium. Conclusion: Although their precise role is yet to be clearly defined, sub-epithelial myofibroblasts are very likely involved in the pathogenesis of Barrett′s metaplasia.

  1. General problems

    International Nuclear Information System (INIS)

    2005-01-01

    This article presents the general problems as natural disasters, consequences of global climate change, public health, the danger of criminal actions, the availability to information about problems of environment

  2. Generalized Recovery

    DEFF Research Database (Denmark)

    Jensen, Christian Skov; Lando, David; Pedersen, Lasse Heje

    We characterize when physical probabilities, marginal utilities, and the discount rate can be recovered from observed state prices for several future time periods. Our characterization makes no assumptions of the probability distribution, thus generalizing the time-homogeneous stationary model...

  3. General Conformity

    Science.gov (United States)

    The General Conformity requirements ensure that the actions taken by federal agencies in nonattainment and maintenance areas do not interfere with a state’s plans to meet national standards for air quality.

  4. Complete Structure of an Epithelial Keratin Dimer: Implications for Intermediate Filament Assembly.

    Directory of Open Access Journals (Sweden)

    David J Bray

    Full Text Available Keratins are cytoskeletal proteins that hierarchically arrange into filaments, starting with the dimer sub-unit. They are integral to the structural support of cells, in skin, hair and nails. In skin, keratin is thought to play a critical role in conferring the barrier properties and elasticity of skin. In general, the keratin dimer is broadly described by a tri-domain structure: a head, a central rod and a tail. As yet, no atomistic-scale picture of the entire dimer structure exists; this information is pivotal for establishing molecular-level connections between structure and function in intermediate filament proteins. The roles of the head and tail domains in facilitating keratin filament assembly and function remain as open questions. To address these, we report results of molecular dynamics simulations of the entire epithelial human K1/K10 keratin dimer. Our findings comprise: (1 the first three-dimensional structural models of the complete dimer unit, comprising of the head, rod and tail domains; (2 new insights into the chirality of the rod-domain twist gained from analysis of the full domain structure; (3 evidence for tri-subdomain partitioning in the head and tail domains; and, (4 identification of the residue characteristics that mediate non-covalent contact between the chains in the dimer. Our findings are immediately applicable to other epithelial keratins, such as K8/K18 and K5/K14, and to intermediate filament proteins in general.

  5. Epithelial-Mesenchymal Transition in Kidney Tubular Epithelial Cells Induced by Globotriaosylsphingosine and Globotriaosylceramide.

    Directory of Open Access Journals (Sweden)

    Yeo Jin Jeon

    Full Text Available Fabry disease is a lysosomal storage disorder caused by deficiency of alpha-galactosidase A (α-gal A, which results in the deposition of globotriaosylceramide (Gb3 in the vascular endothelium. Globotriaosylsphingosine (lyso-Gb3, a deacylated Gb3, is also increased in the plasma of patients with Fabry disease. Renal fibrosis is a key feature of advanced Fabry disease patients. Therefore, we evaluated the association of Gb3 and lyso-Gb3 accumulation and the epithelial-mesenchymal transition (EMT on tubular epithelial cells of the kidney. In HK2 cells, exogenous treatments of Gb3 and lyso-Gb3 increased the expression of TGF-β, EMT markers (N-cadherin and α-SMA, and phosphorylation of PI3K/AKT, and decreased the expression of E-cadherin. Lyso-Gb3, rather than Gb3, strongly induced EMT in HK2 cells. In the mouse renal mesangial cell line, SV40 MES 13 cells, Gb3 strongly induced phenotype changes. The EMT induced by Gb3 was inhibited by enzyme α-gal A treatment, but EMT induced by lyso-Gb3 was not abrogated by enzyme treatment. However, TGF-β receptor inhibitor (TRI, SB525334 inhibited the activation of TGF-β and EMT markers in HK2 cells with Gb3 and lyso-Gb3 treatments. This study suggested that increased plasma lyso-Gb3 has a crucial role in the development of renal fibrosis through the cell-specific induction of the EMT in Fabry disease, and that TRI treatment, alongside enzyme replacement therapy, could be a potential therapeutic option for patients with Fabry disease.

  6. Variant BDNF-Val66Met Polymorphism is Associated with Layer-Specific Alterations in GABAergic Innervation of Pyramidal Neurons, Elevated Anxiety and Reduced Vulnerability of Adolescent Male Mice to Activity-Based Anorexia.

    Science.gov (United States)

    Chen, Yi-Wen; Surgent, Olivia; Rana, Barkha S; Lee, Francis; Aoki, Chiye

    2017-08-01

    Previously, we determined that rodents' vulnerability to food restriction (FR)-evoked wheel running during adolescence (activity-based anorexia, ABA) is associated with failures to increase GABAergic innervation of hippocampal and medial prefrontal pyramidal neurons. Since brain-derived neurotrophic factor (BDNF) promotes GABAergic synaptogenesis, we hypothesized that individual differences in this vulnerability may arise from differences in the link between BDNF bioavailability and FR-evoked wheel running. We tested this hypothesis in male BDNF-Val66Met knock-in mice (BDNFMet/Met), known for reduction in the activity-dependent BDNF secretion and elevated anxiety-like behaviors. We found that 1) in the absence of FR or a wheel (i.e., control), BDNFMet/Met mice are more anxious than wild-type (WT) littermates, 2) electron microscopically verified GABAergic innervations of pyramidal neurons of BDNFMet/Met mice are reduced at distal dendrites in hippocampal CA1 and medial prefrontal cortex, 3) following ABA, WT mice exhibit anxiety equal to those of the BDNFMet/Met mice and have lost GABAergic innervation along distal dendrites, 4) BDNFMet/Met mice show blunted ABA vulnerability, and 5) unexpectedly, GABAergic innervation is higher at somata of BDNFMet/Met mice than of WT. We conclude that lamina-specific GABAergic inhibition is important for regulating anxiety, whether arising from environmental stress, such as food deprivation, or genetically, such as BDNFMet/Met single nucleotide polymorphism. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Collagen organization regulates stretch-initiated pain-related neuronal signals in vitro: Implications for structure-function relationships in innervated ligaments.

    Science.gov (United States)

    Zhang, Sijia; Singh, Sagar; Winkelstein, Beth A

    2018-02-01

    Injury to the spinal facet capsule, an innervated ligament with heterogeneous collagen organization, produces pain. Although mechanical facet joint trauma activates embedded afferents, it is unclear if, and how, the varied extracellular microstructure of its ligament affects sensory transduction for pain from mechanical inputs. To investigate the effects of macroscopic deformations on afferents in collagen matrices with different organizations, an in vitro neuron-collagen construct (NCC) model was used. NCCs with either randomly organized or parallel aligned collagen fibers were used to mimic the varied microstructure in the facet capsular ligament. Embryonic rat dorsal root ganglia (DRG) were encapsulated in the NCCs; axonal outgrowth was uniform and in all directions in random NCCs, but parallel in aligned NCCs. NCCs underwent uniaxial stretch (0.25 ± 0.06 strain) corresponding to sub-failure facet capsule strains that induce pain. Macroscopic NCC mechanics were measured and axonal expression of phosphorylated extracellular signal-regulated kinase (pERK) and the neurotransmitter substance P (SP) was assayed at 1 day to assess neuronal activation and nociception. Stretch significantly upregulated pERK expression in both random and aligned gels (p organization. These findings suggest that collagen organization differentially modulates pain-related neuronal signaling and support structural heterogeneity of ligament tissue as mediating sensory function. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:770-777, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  8. Impact of sympathetic innervation on recurrent life-threatening arrhythmias in the follow-up of patients with idiopathic ventricular fibrillation

    Energy Technology Data Exchange (ETDEWEB)

    Paul, Matthias; Acil, Tayfun; Breithardt, Guenter; Wichter, Thomas [Hospital of the University of Muenster, Department of Cardiology and Angiology, Muenster (Germany); Schaefers, Michael; Kies, Peter; Schaefers, Klaus; Schober, Otmar [Hospital of the University of Muenster, Department of Nuclear Medicine, Muenster (Germany)

    2006-08-15

    Idiopathic ventricular fibrillation (IVF) is defined as VF in the absence of any identifiable structural or functional cardiac disease. The underlying pathophysiological mechanisms are unknown. This study was performed to investigate the potential impact of sympathetic dysfunction, assessed by {sup 123}I-meta-iodo-benzylguanidine scintigraphy ({sup 123}I-MIBG SPECT), on the long-term prognosis of patients with IVF. {sup 123}I-MIBG SPECT was performed in 20 patients (mean age 37{+-}13 years) with IVF. Mean follow-up of patients after study entry was 7.2{+-}1.5 years (range 4.9-10.5 years). Ten patients (five men, five women; mean age 43{+-}12 years; p=NS versus study group) with medullary carcinoma of the thyroid gland served as an age-matched control group. Abnormal {sup 123}I-MIBG uptake was observed in 13 patients (65%). During follow-up, 18 episodes of VF/fast polymorphic ventricular tachycardias occurred in four IVF patients with abnormal {sup 123}I-MIBG uptake whereas only two episodes of monomorphic ventricular tachycardia (and no VF) occurred in a single IVF patient with normal {sup 123}I-MIBG uptake. Impairment of sympathetic innervation may indicate a higher risk of future recurrent episodes of life-threatening ventricular tachyarrhythmias in patients with IVF. Studies in larger cohorts are required to validate the significance of {sup 123}I-MIBG SPECT during the long-term follow-up of these patients. (orig.)

  9. Bilateral irradiation of head and neck induces and enhanced expression of substance P in the parasympathetic innervation of the submandibular gland

    Energy Technology Data Exchange (ETDEWEB)

    Forsgren, S; Franzen, L; Funegard, U; Gustafsson, H; Henriksson, R [Umeaa Univ. (Sweden). Dept. of Oncology, Anatomy and Oto-laryngology

    1992-01-01

    Substance P and calcitonin gene-related peptide (CGRP) are present in nerve fibers innervating the submandibular gland. Radiotherapy of tumours in the head and neck region usually embraces the salivary glands in the irradiated field and consequently a dramatic decrease in salivary function is seen. In this study, the submandibular glands and ganglia of rats subjected to fractionated irradiation were examined by use of immunohistochemical techniques for demonstration of substance P and CGRP. Irradiation was given on five consecutive days with unilateral or bilateral irradiation techniques. Specimens of control and experimental animals were processed in parallel. A marked increase in the expression of substance P in the ganglionic cells-presumably parasympathetic-and in the number of fibers showing substance P-like immunoreactivity in association with acini and small ducts was seen in response to bilateral irradiation. No changes in the pattern of CGRP immunoreactivity occurred. In the trigeminal ganglion, which supplies the submandibular gland with the majority of the sensory substance P-and CGRP-containing nerve fibers, no changes in the expression of substance P or CGRP immunoreactivity were seen. The results suggest that bilateral irradiation leads to an increase in the synthesis of substance P-like substance in the parasympathetic ganglionic cells supplying the submandibular gland with secretory nerves, and can thus be an additional factor in explaining the altered secretory capacity of salivary glands. (author).

  10. Fascicular Phrenic Nerve Neurotization for Restoring Physiological Motion in a Congenital Diaphragmatic Hernia Reconstruction With a Reverse Innervated Latissimus Dorsi Muscle Flap.

    Science.gov (United States)

    Horta, Ricardo; Henriques-Coelho, Tiago; Costa, Joana; Estevão-Costa, José; Monteiro, Diana; Dias, Mariana; Braga, José; Silva, Alvaro; Azevedo, Inês; Amarante, José Manuel

    2015-08-01

    Congenital diaphragmatic hernia is a severe developmental anomaly characterized by the malformation of the diaphragm. An innervated reversed latissimus dorsi flap reconstruction for recurrent congenital diaphragmatic hernia has been described as an alternative to prosthetic patch repair to achieve pleuroperitoneal separation. However, there is very little supporting scientific data; therefore, there is no real basic understanding of the condition of the phrenic nerve in the absence of diaphragmatic muscle or even the neurotization options for restoring neodiaphragmatic muscle motion. We have reviewed the literature regarding phrenic nerve anatomy and neurotization options, and to our knowledge, this is the first time that the application of a fascicular repair is being described where the continuity of one remaining fascicle of the diaphragm has been preserved close to the phrenic nerve distal division. The procedure was undertaken in a 3 year-old boy, with the diagnosis of congenital large posteromedial diaphragmatic hernia and dependence of mechanical ventilation in consequence of severe bronchopulmonary dysplasia.The phrenic nerve divides itself into several terminal branches, usually three, at the diaphragm level, or just above it. This allows the selective coaptation of separate fascicular branches. In the case described, videofluoroscopy evaluation showed no evidence of paradoxical neodiaphragmatic motion, with synchronous contraction movements and intact pleura-peritoneal separation. The child is now asymptomatic and shows improvement of his previous restrictive pulmonary disease.We believe that fascicular repair can achieve some reinnervation of the flap without jeopardizing the potential of diaphragmatic function by contraction of reminiscent native diaphragm.

  11. Gender differences in nigrostriatal dopaminergic innervation are present at young-to-middle but not at older age in normal adults.

    Science.gov (United States)

    Wong, Ka Kit; Müller, Martijn L T M; Kuwabara, Hiroto; Studenski, Stephanie A; Bohnen, Nicolaas I

    2012-01-01

    Gender differences in brain dopaminergic activity have been variably reported in the literature. We performed an evaluation for gender effects on striatal dopamine transporter (DAT) binding in a group of normal subjects. Community-dwelling adults (n = 85, 50F/35M, mean age 62.7 ± 16.2 SD, range 20-85) underwent DAT [(11)C]2-β-carbomethoxy-3β-(4-fluorophenyl) tropane (β-CFT) positron emission tomography (PET) imaging. Gender effects for DAT binding were compared using ANCOVA for two subgroups; young-to-middle aged adults and older adults, using an age threshold of 60 years. There were 54 subjects (24M/30F; mean age 72.9 ± 7.3) 60 years and older and 31 (11M/20F; mean age 45.0 ± 11.4) subjects younger than 60. Age-adjusted striatal DAT gender effects were present in the young-to-middle (F = 10.4, P = 0.003) but not in the elderly age group (F = 0.5, ns). Gender differences in nigrostriatal dopaminergic innervation are present, with higher levels of DAT binding in young-to-middle age women compared to men, but not present in the elderly. Published by Elsevier Ltd.

  12. Multifocal epithelial hyperplasia: a forgotten condition in the elderly.

    Science.gov (United States)

    Shamloo, Nafiseh; Mortazavi, Hamed; Taghavi, Nasim; Baharvand, Maryam

    2016-01-01

    Multifocal epithelial hyperplasia (MEH), also known as focal epithelial hyperplasia and Heck disease, is a relatively rare condition caused by the human papillomavirus. This case report describes a 92-year-old man who presented with multiple, asymptomatic, circumscribed, soft, flattened papules in different sizes on the retrocommissure of his lower lip. The lesions were of 2 months' duration and had the same coloration as the adjacent normal mucosa. Histopathologic examination showed orthokeratinized stratified squamous epithelium with acanthosis, some areas of club-shaped rete ridges, and a few superficial epithelial cells with koilocytic changes and a mitosoid-like appearance. A diagnosis of MEH was established. Although MEH tends to occur in the first 2 decades of life, it can be encountered in elderly patients as well.

  13. Maxillary bone epithelial cyst in an adult miniature schnauzer.

    Science.gov (United States)

    Lin, Chung-Tien; Tasi, Wen-Chih; Hu, Chun-Kun; Lin, Nien-Ting; Huang, Pei-Yun; Yeh, Lih-Seng

    2008-09-01

    Maxillary bone epithelial cyst is rare in dogs. A 5-year-old, spayed female miniature schnauzer developed a swelling below the nasal canthus of left eye. Plain radiograph demonstrated a 1.5 cm diameter of radiolucent lesion on the maxillary bone anteroventral to the eye, and contrast dacryocystorhinography confirmed an obstructed nasolarcrimal duct. The swelling showed poor response to antibiotic treatment but responded well to oral prednisolone. Exploratory surgery revealed a cyst-like structure filled with brown serous fluid. Histopathological examination of the removed cyst revealed a double cuboidal epithelial cyst. The dog recovered rapidly after surgery, and the swelling had not recurred for a 36-month follow-up. It is the first case of periorbital bone epithelial cyst reported in an adult miniature schnauzer.

  14. Epithelial-mesenchymal transition: Understanding the basic concept

    Directory of Open Access Journals (Sweden)

    Suresh Babu Ghanta

    2012-01-01

    Full Text Available The epithelial-mesenchymal transition (EMT is described as a rapid and reversible process of change of cell phenotype seen during embryonic development, organ fibrosis, and tumor progression. EMT was first described by Gary Greenberg and Elizabeth Hay in 1982. During EMT the epithelial cells alter their cell polarity, reorganize their cytoskeleton thus become isolated and motile. Depending upon the biological context in which they occur, EMT is divided into three types namely EMT type I, II, III. The article describes the process of EMT implicated in the oral cavity as in palate and root development (type I EMT, gingival fibromatosis and oral sub-mucous fibrosis (type II EMT, and oral squamous cell carcinoma (type III EMT. The reverse process of EMT is called as mesenchymal-epithelial transition seen in association with kidney formation.

  15. High-grain diets altered rumen fermentation and epithelial bacterial community and resulted in rumen epithelial injuries of goats.

    Science.gov (United States)

    Zhang, Ruiyang; Ye, Huimin; Liu, Junhua; Mao, Shengyong

    2017-09-01

    This study evaluated the effects of high-grain diets on the rumen fermentation, epithelial bacterial community, morphology of rumen epithelium, and local inflammation of goats during high-grain feeding. Twelve 8-month-old goats were randomly assigned to two different diets, a hay diet or a high-grain diet (65% grain, HG). At the end of 7 weeks of treatment, samples of rumen content and rumen epithelium were collected. Rumen pH was lower (P rumen epithelial bacterial community, with an increase in the proportion of genus Prevotella and a decrease in the relative abundance of the genera Shuttleworthia and Fibrobacteres. PICRUSt analysis suggested that the HG-fed group had a higher (P rumen epithelial injury and upregulated (P rumen pH, LPS level, and rumen epithelial bacteria abundance. In conclusion, our results indicated that the alterations in the rumen environment and epithelial bacterial community which were induced by HG feeding may result in the damage and local inflammation in the rumen epithelium, warranting further study of rumen microbial-host interactions in the HG feeding model.

  16. Emodin suppresses TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells through Notch signaling pathway

    International Nuclear Information System (INIS)

    Gao, Rundi; Chen, Ruilin; Cao, Yu; Wang, Yuan; Song, Kang; Zhang, Ya; Yang, Junchao

    2017-01-01

    Pulmonary fibrosis is characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicament on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been established yet. In the present study, we investigated the hypothesis that Emodin plays an inhibitory role in TGF-β1 induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cell, and Emodin exerts its effect through the Notch signaling pathway. Emodin inhibits the proliferation of Rat alveolar type II epithelial cells RLE-6TN in a concentration-dependent manner; reduces the expression of Collagen I, α-SMA and Vimentin, promotes the expression of E-cadherin. Moreover, Emodin could regulate the expression patterns of the Notch signaling pathway-related factors and reduce the Notch-1 nucleus translocation. Knockdown of Notch-1 enhances the inhibitory effect of Emodin on TGF-β1-induced EMT in RLE-6TN cells. In conclusion, the data of the present study suggests that Emodin suppresses TGF-β1-induced EMT in alveolar epithelial cells through Notch signaling pathway and shows the potential to be effective in the treatment of pulmonary fibrosis. - Highlights: • Emodin inhibits TGF-β1-induced EMT in alveolar epithelial cells. • Emodin regulates the expression patterns of the Notch signaling pathway-related factors. • Emodin inhibits TGF-β1-induced Notch-1 nucleus translocation and activation.

  17. Emodin suppresses TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells through Notch signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Rundi; Chen, Ruilin; Cao, Yu [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Wang, Yuan [Department of Pulmonary Function, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Song, Kang [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Zhang, Ya [Zhejiang Chinese Medicine University, No. 548, Binwen Road, Binjiang District, Hangzhou, Zhejiang Province 310006 (China); Yang, Junchao, E-mail: yangjunchaozj@zcmu.edu.cn [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China)

    2017-03-01

    Pulmonary fibrosis is characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicament on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been established yet. In the present study, we investigated the hypothesis that Emodin plays an inhibitory role in TGF-β1 induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cell, and Emodin exerts its effect through the Notch signaling pathway. Emodin inhibits the proliferation of Rat alveolar type II epithelial cells RLE-6TN in a concentration-dependent manner; reduces the expression of Collagen I, α-SMA and Vimentin, promotes the expression of E-cadherin. Moreover, Emodin could regulate the expression patterns of the Notch signaling pathway-related factors and reduce the Notch-1 nucleus translocation. Knockdown of Notch-1 enhances the inhibitory effect of Emodin on TGF-β1-induced EMT in RLE-6TN cells. In conclusion, the data of the present study suggests that Emodin suppresses TGF-β1-induced EMT in alveolar epithelial cells through Notch signaling pathway and shows the potential to be effective in the treatment of pulmonary fibrosis. - Highlights: • Emodin inhibits TGF-β1-induced EMT in alveolar epithelial cells. • Emodin regulates the expression patterns of the Notch signaling pathway-related factors. • Emodin inhibits TGF-β1-induced Notch-1 nucleus translocation and activation.

  18. Generalized polygons

    CERN Document Server

    Van Maldeghem, Hendrik

    1998-01-01

    Generalized Polygons is the first book to cover, in a coherent manner, the theory of polygons from scratch. In particular, it fills elementary gaps in the literature and gives an up-to-date account of current research in this area, including most proofs, which are often unified and streamlined in comparison to the versions generally known. Generalized Polygons will be welcomed both by the student seeking an introduction to the subject as well as the researcher who will value the work as a reference. In particular, it will be of great value for specialists working in the field of generalized polygons (which are, incidentally, the rank 2 Tits-buildings) or in fields directly related to Tits-buildings, incidence geometry and finite geometry. The approach taken in the book is of geometric nature, but algebraic results are included and proven (in a geometric way!). A noteworthy feature is that the book unifies and generalizes notions, definitions and results that exist for quadrangles, hexagons, octagons - in the ...

  19. Hypo-responsiveness of interleukin-8 production in human embryonic epithelial intestine 407 cells independent of NF-κB pathway: New lessons from endotoxin and ribotoxic deoxynivalenol

    International Nuclear Information System (INIS)

    Moon, Yuseok; Yang, Hyun; Park, Seung-Hwan

    2008-01-01

    Mucosal epithelium senses external toxic insults and transmits the danger signals into the epithelial cells in order to activate a broad range of inflammatory responses. However, pre-exposure to the commensal endotoxins can induce inflammatory tolerance and maintain the homeostasis without excessive immune responses. We recently reported that ribotoxin deoxynivalenol (DON) and its derivatives elicited the pro-inflammatory response as the mucosal insults in human epithelial cells. Taking the knowledge into consideration, we tested the hypothesis that endotoxin pre-exposure can attenuate ribotoxin-induced epithelial interleukin-8 (IL-8) production via a tolerance mechanism. Pre-exposure to endotoxin repressed IL-8 release and its gene expression. However, inflammatory tolerance was not mediated by the attenuated NF-κB activation which has been generally recognized as the major mediator of LPS-mediated toll-like receptor (TLR) signaling pathway. Instead, pre-exposure to endotoxin was observed to trigger the delayed induction of peroxisome proliferator-activated receptor gamma (PPAR-γ) which contributed to the diminished IL-8 production in the human epithelial cells. Moreover, endogenous PPAR-γ agonist suppressed toxicant-mediated interleukin-8 production and IL-8 mRNA stability. Taken together, endotoxin induced hypo-production of pro-inflammatory cytokine IL-8 in the human epithelial cells, which was associated with the delayed activation of PPAR-γ expression by pre-existing endotoxin

  20. AMP-18 Targets p21 to Maintain Epithelial Homeostasis.

    Science.gov (United States)

    Chen, Peili; Li, Yan Chun; Toback, F Gary

    2015-01-01

    Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD). We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP)-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI) mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD.

  1. AMP-18 Targets p21 to Maintain Epithelial Homeostasis.

    Directory of Open Access Journals (Sweden)

    Peili Chen

    Full Text Available Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD. We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD.

  2. Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis

    DEFF Research Database (Denmark)

    Wendland, Kerstin; Niss, Kristoffer; Kotarsky, Knut

    2018-01-01

    Despite the essential role of thymic epithelial cells (TEC) in T cell development, the signals regulating TEC differentiation and homeostasis remain incompletely understood. In this study, we show a key in vivo role for the vitamin A metabolite, retinoic acid (RA), in TEC homeostasis. In the abse......Despite the essential role of thymic epithelial cells (TEC) in T cell development, the signals regulating TEC differentiation and homeostasis remain incompletely understood. In this study, we show a key in vivo role for the vitamin A metabolite, retinoic acid (RA), in TEC homeostasis...

  3. From cells to tissue: A continuum model of epithelial mechanics

    Science.gov (United States)

    Ishihara, Shuji; Marcq, Philippe; Sugimura, Kaoru

    2017-08-01

    A two-dimensional continuum model of epithelial tissue mechanics was formulated using cellular-level mechanical ingredients and cell morphogenetic processes, including cellular shape changes and cellular rearrangements. This model incorporates stress and deformation tensors, which can be compared with experimental data. Focusing on the interplay between cell shape changes and cell rearrangements, we elucidated dynamical behavior underlying passive relaxation, active contraction-elongation, and tissue shear flow, including a mechanism for contraction-elongation, whereby tissue flows perpendicularly to the axis of cell elongation. This study provides an integrated scheme for the understanding of the orchestration of morphogenetic processes in individual cells to achieve epithelial tissue morphogenesis.

  4. Polarized Airway Epithelial Models for Immunological Co-Culture Studies

    DEFF Research Database (Denmark)

    Papazian, Dick; Würtzen, Peter A; Hansen, Søren Werner Karlskov

    2016-01-01

    Epithelial cells line all cavities and surfaces throughout the body and play a substantial role in maintaining tissue homeostasis. Asthma and other atopic diseases are increasing worldwide and allergic disorders are hypothesized to be a consequence of a combination of dysregulation...... of the epithelial response towards environmental antigens and genetic susceptibility, resulting in inflammation and T cell-derived immune responses. In vivo animal models have long been used to study immune homeostasis of the airways but are limited by species restriction and lack of exposure to a natural...

  5. Epithelial-mesenchymal transition: An emerging target in tissue fibrosis

    Science.gov (United States)

    Li, Meirong; Luan, Fuxin; Zhao, Yali; Hao, Haojie; Zhou, Yong; Han, Weidong

    2016-01-01

    Epithelial-mesenchymal transition (EMT) is involved in a variety of tissue fibroses. Fibroblasts/myofibroblasts derived from epithelial cells contribute to the excessive accumulation of fibrous connective tissue in damaged tissue, which can lead to permanent scarring or organ malfunction. Therefore, EMT-related fibrosis cannot be neglected. This review highlights the findings that demonstrate the EMT to be a direct contributor to the fibroblast/myofibroblast population in the development of tissue fibrosis and helps to elucidate EMT-related anti-fibrotic strategies, which may enable the development of therapeutic interventions to suppress EMT and potentially reverse organ fibrosis. PMID:26361988

  6. Human thymic epithelial cells express functional HLA-DP molecules

    DEFF Research Database (Denmark)

    Jørgensen, A; Röpke, C; Nielsen, M

    1996-01-01

    T lymphocytes, we examined whether human thymic epithelial cells (TEC) expressed HLA-DP molecules. We present evidence that TEC obtained from short time culture express low but significant levels of HLA-DP molecules. The expression of HLA-DP molecules was comparable to or higher than the expression...... of HLA-DP allospecific primed lymphocyte typing (PLT) CD4 T cell lines. IFN-gamma treatment strongly upregulated the HLA-DP allospecific PLT responses whereas other PLT responses remained largely unchanged. In conclusion, these data indicate that human thymus epithelial cells express significant levels...

  7. Primary Surgery or Interval Debulking for Advanced Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

    Markauskas, Algirdas; Mogensen, Ole; dePont Christensen, René

    2014-01-01

    OBJECTIVE: The aim of the present study was to investigate the surgical complexity, the postoperative morbidity, and the survival of the women after primary debulking surgery (PDS) and neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for advanced epithelial ovarian cancer....... MATERIALS AND METHODS: We consecutively included all patients who underwent debulking surgery at our institution between January 2007 and December 2012 for stages IIIc and IV of epithelial ovarian cancer. RESULTS: Of the 332 patients included, 165 (49.7%) underwent PDS, and 167 (50.3%) had NACT...

  8. Calcifying epithelial odontogenic cyst with odontome in left mandible

    Directory of Open Access Journals (Sweden)

    R Kamala

    2009-01-01

    Full Text Available Calcifying epithelial odontogenic cyst is a mixed odontogenic benign tumor but most of the cases present cystic characteristics. We present a case report of calcifying epithelial odontogenic cyst with odontoma in a 20-year-old male who presented with a painless unilateral swelling of the jaw. The lesion involved an impacted 37 which was displaced to the lower border of the mandible and a calcified mass that was within the cystic lesion that was recognized as odontoma. The lesion was surgically removed along with 36 and 37 was allowed to erupt.

  9. Epithelial-to-Mesenchymal Transition in Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Carla Cano

    2010-01-01

    Full Text Available Epithelial to mesenchymal transition (EMT is a physiologic process that allows morphological and genetic changes of carcinoma cells from an epithelial to a mesenchymal phenotype, which is the basis of the high metastatic potential of pancreatic cancer cells. EMT is triggered by various tumor microenvironmental factors, including cytokines, growth factors, and chemotherapeutic agents. This review summarizes the state-of-the-art knowledge on the molecular mechanisms that support pancreatic cancer EMT and the evidences that support its involvement in invasiveness/aggressiveness, and the drug resistance of pancreatic cancer cells.

  10. General conclusions

    International Nuclear Information System (INIS)

    Tubiana, M.

    1993-01-01

    In conclusion, a general consensus of a number of points which the author endeavours to summarize in this article: -doctors are an excellent channel for passing on information to the public -doctors feel that they do not know enough about the subject and a training on radiobiology and radiation protection is a necessity for them -communication between doctors and the general public is poor in this field -research should be encouraged in numerous areas such as: carcinogenic effect of low doses of radiation, pedagogy and risk perception

  11. An optimized protocol for isolating primary epithelial cell chromatin for ChIP.

    Directory of Open Access Journals (Sweden)

    James A Browne

    Full Text Available A critical part of generating robust chromatin immunoprecipitation (ChIP data is the optimization of chromatin purification and size selection. This is particularly important when ChIP is combined with next-generation sequencing (ChIP-seq to identify targets of DNA-binding proteins, genome-wide. Current protocols refined by the ENCODE consortium generally use a two-step cell lysis procedure that is applicable to a wide variety of cell types. However, the isolation and size selection of chromatin from primary human epithelial cells may often be particularly challenging. These cells tend to form sheets of formaldehyde cross-linked material in which cells are resistant to membrane lysis, nuclei are not released and subsequent sonication produces extensive high molecular weight contamination. Here we describe an optimized protocol to prepare high quality ChIP-grade chromatin from primary human bronchial epithelial cells. The ENCODE protocol was used as a starting point to which we added the following key steps to separate the sheets of formaldehyde-fixed cells prior to lysis. (1 Incubation of the formaldehyde-fixed adherent cells in Trypsin-EDTA (0.25% room temperature for no longer than 5 min. (2 Equilibration of the fixed cells in detergent-free lysis buffers prior to each lysis step. (3 The addition of 0.5% Triton X-100 to the complete cell membrane lysis buffer. (4 Passing the cell suspension (in complete cell membrane lysis buffer through a 25-gauge needle followed by continuous agitation on ice for 35 min. Each step of the modified protocol was documented by light microscopy using the Methyl Green-Pyronin dual dye, which stains cytoplasm red (Pyronin and the nuclei grey-blue (Methyl green. This modified method is reproducibly effective at producing high quality sheared chromatin for ChIP and is equally applicable to other epithelial cell types.

  12. Construction of predictive promoter models on the example of antibacterial response of human epithelial cells

    Directory of Open Access Journals (Sweden)

    Wingender Edgar

    2005-01-01

    Full Text Available Abstract Background Binding of a bacteria to a eukaryotic cell triggers a complex network of interactions in and between both cells. P. aeruginosa is a pathogen that causes acute and chronic lung infections by interacting with the pulmonary epithelial cells. We use this example for examining the ways of triggering the response of the eukaryotic cell(s, leading us to a better understanding of the details of the inflammatory process in general. Results Considering a set of genes co-expressed during the antibacterial response of human lung epithelial cells, we constructed a promoter model for the search of additional target genes potentially involved in the same cell response. The model construction is based on the consideration of pair-wise combinations of transcription factor binding sites (TFBS. It has been shown that the antibacterial response of human epithelial cells is triggered by at least two distinct pathways. We therefore supposed that there are two subsets of promoters activated by each of them. Optimally, they should be "complementary" in the sense of appearing in complementary subsets of the (+-training set. We developed the concept of complementary pairs, i.e., two mutually exclusive pairs of TFBS, each of which should be found in one of the two complementary subsets. Conclusions We suggest a simple, but exhaustive method for searching for TFBS pairs which characterize the whole (+-training set, as well as for complementary pairs. Applying this method, we came up with a promoter model of antibacterial response genes that consists of one TFBS pair which should be found in the whole training set and four complementary pairs. We applied this model to screening of 13,000 upstream regions of human genes and identified 430 new target genes which are potentially involved in antibacterial defense mechanisms.

  13. Demographic and histopathological patterns of neuro-epithelial brain tumors in Eastern Province of Saudi Arabia.

    Science.gov (United States)

    Taha, Mahmoud S; Almsned, Fahad M; Hassen, Mohammed A; Atean, Ibrahim M; Alwbari, Ahmed M; Alharbi, Qasim K; Abdulkader, Marwah M; Almuhaish, Husam S

    2018-01-01

    To review the demographic and pathological pattern of neuro-epithelial brain tumors in a tertiary referral center in the Eastern Province of Saudi Arabia and to compare the results of our study with other national and international studies. This is a retrospective chart-review study of all patients with neuro-epithelial brain tumors referred and treated in our center between January 2010 and January 2015. The age, gender, tumor location, and histopathology were recorded. The total number of cases was 149 including 96 adult cases and 53 pediatric cases. 58% of cases were male, and 42% were female. The age group distribution showed 2 peaks; one in the first 5 years of life and the second was in the age range from 26-45 years old. Glioblastoma multiforme was the most common pathological type (32%), followed by medulloblastoma (13.3%). This study showed similar results to a previous study conducted in the Eastern Province in terms of age and gender distribution, but pathologically, the tumors diagnosed in our study were generally of a higher grading. When comparing our results to other international studies in nearby countries (Jordan and Egypt), we found similarities in pathological patterns and age distribution. However, when comparing our results to a western country (USA), we found considerable differences in the age group distribution. Neuro-epithelial brain tumors in Saudi Arabia affect younger population according to our study compared to Western countries. These findings are similar to other studies from Middle Eastern countries. In addition, our study showed a significant increase in high grade gliomas in the Eastern Province compared to an old historical study. This increase should be interpreted cautiously due to possible selection errors, changes in pathological grading, and expertise.

  14. GENERAL Iarticle

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 8; Issue 2. Supersymmetry. Akshay Kulkarni P Ramadevi. General Article Volume 8 Issue 2 February 2003 pp 28-41 ... Author Affiliations. Akshay Kulkarni1 P Ramadevi1. Physics Department, Indian Institute of Technology, Mumbai 400 076, India.

  15. General indicators

    International Nuclear Information System (INIS)

    2003-01-01

    This document summarizes the main 2002 energy indicators for France. A first table lists the evolution of general indicators between 1973 and 2002: energy bill, price of imported crude oil, energy independence, primary and final energy consumption. The main 2002 results are detailed separately for natural gas, petroleum and coal (consumption, imports, exports, production, stocks, prices). (J.S.)

  16. Generalized Recovery

    DEFF Research Database (Denmark)

    Jensen, Christian Skov; Lando, David; Pedersen, Lasse Heje

    We characterize when physical probabilities, marginal utilities, and the discount rate can be recovered from observed state prices for several future time periods. We make no assumptions of the probability distribution, thus generalizing the time-homogeneous stationary model of Ross (2015). Recov...

  17. GENERAL SURGERY

    African Journals Online (AJOL)

    Department of Surgery, University of Cape Town Health Sciences Faculty, Groote Schuur Hospital, Observatory, Cape Town,. South Africa ... included all district, regional and tertiary hospitals in the nine provinces. Clinics and so-called ..... large contingency of senior general surgeons from countries such as Cuba, who have ...

  18. GENERAL SURGERY

    African Journals Online (AJOL)

    effect of fatigue on patient safety, and owing to increasing emphasis on lifestyle issues .... increasing emphasis on an appropriate work-life balance in professional life.10 ... experience, were the most negative about the EWTD in general.3,13 ...

  19. GENERAL SURGERY

    African Journals Online (AJOL)

    in the endoscopy room. GENERAL SURGERY. T du Toit, O C Buchel, S J A Smit. Department of Surgery, University of the Free State, Bloemfontein, ... The lack of video instrumentation in developing countries: Redundant fibre-optic instruments (the old. “eye scope”) are still being used. This instrument brings endoscopists ...

  20. General Assembly

    CERN Multimedia

    Staff Association

    2016-01-01

    5th April, 2016 – Ordinary General Assembly of the Staff Association! In the first semester of each year, the Staff Association (SA) invites its members to attend and participate in the Ordinary General Assembly (OGA). This year the OGA will be held on Tuesday, April 5th 2016 from 11:00 to 12:00 in BE Auditorium, Meyrin (6-2-024). During the Ordinary General Assembly, the activity and financial reports of the SA are presented and submitted for approval to the members. This is the occasion to get a global view on the activities of the SA, its financial management, and an opportunity to express one’s opinion, including taking part in the votes. Other points are listed on the agenda, as proposed by the Staff Council. Who can vote? Only “ordinary” members (MPE) of the SA can vote. Associated members (MPA) of the SA and/or affiliated pensioners have a right to vote on those topics that are of direct interest to them. Who can give his/her opinion? The Ordinary General Asse...

  1. GENERAL SURGERY

    African Journals Online (AJOL)

    could cripple the global economy. Greater attention ... Africa and 5.7 general surgeons per 100 000 in the US.12 One of the key ... 100 000 insured population working in the private sector, which is comparable with the United States (US).

  2. Necklaces: Generalizations

    Indian Academy of Sciences (India)

    IAS Admin

    . A q-ary necklace of length n is an equivalence class of q-coloured strings of length n under rota- tion. In this article, we study various generaliza- tions and derive analytical expressions to count the number of these generalized necklaces.

  3. Generalized Recovery

    DEFF Research Database (Denmark)

    Lando, David; Pedersen, Lasse Heje; Jensen, Christian Skov

    We characterize when physical probabilities, marginal utilities, and the discount rate can be recovered from observed state prices for several future time periods. We make no assumptions of the probability distribution, thus generalizing the time-homogeneous stationary model of Ross (2015...... our model empirically, testing the predictive power of the recovered expected return and other recovered statistics....

  4. General Relativity

    CERN Document Server

    Straumann, Norbert

    2013-01-01

    This book provides a completely revised and expanded version of the previous classic edition ‘General Relativity and Relativistic Astrophysics’. In Part I the foundations of general relativity are thoroughly developed, while Part II is devoted to tests of general relativity and many of its applications. Binary pulsars – our best laboratories for general relativity – are studied in considerable detail. An introduction to gravitational lensing theory is included as well, so as to make the current literature on the subject accessible to readers. Considerable attention is devoted to the study of compact objects, especially to black holes. This includes a detailed derivation of the Kerr solution, Israel’s proof of his uniqueness theorem, and a derivation of the basic laws of black hole physics. Part II ends with Witten’s proof of the positive energy theorem, which is presented in detail, together with the required tools on spin structures and spinor analysis. In Part III, all of the differential geomet...

  5. Mechanisms of Cell Polarity-Controlled Epithelial Homeostasis and Immunity in the Intestine

    NARCIS (Netherlands)

    Klunder, Leon J.; Faber, Klaas Nico; Dijkstra, Gerard; van IJzendoorn, Sven C. D.

    Intestinal epithelial cell polarity is instrumental to maintain epithelial homeostasis and balance communications between the gut lumen and bodily tissue, thereby controlling the defense against gastrointestinal pathogens and maintenance of immune tolerance to commensal bacteria. In this review, we

  6. Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage

    NARCIS (Netherlands)

    P. Aparicio-Domingo (Patricia); M. Romera Hernández (Mónica); J.J. Karrich (Julien J.); F.H.J. Cornelissen (Ferry); N. Papazian (Natalie); D.J. Lindenbergh-Kortleve (Dicky); J.A. Butler (James A.); L. Boon (Louis); M. Coles (Mark); J.N. Samsom (Janneke); T. Cupedo (Tom)

    2015-01-01

    textabstractDisruption of the intestinal epithelial barrier allows bacterial translocation and predisposes to destructive inflammation. To ensure proper barrier composition, crypt-residing stem cells continuously proliferate and replenish all intestinal epithelial cells within days. As a consequence

  7. Chronic regulation of colonic epithelial secretory function by activation of G protein-coupled receptors.

    LENUS (Irish Health Repository)

    Toumi, F

    2011-02-01

    Enteric neurotransmitters that act at G protein-coupled receptors (GPCRs) are well known to acutely promote epithelial Cl(-) and fluid secretion. Here we examined if acute GPCR activation might have more long-term consequences for epithelial secretory function.

  8. CXCL9 Regulates TGF-β1-Induced Epithelial to Mesenchymal Transition in Human Alveolar Epithelial Cells.

    Science.gov (United States)

    O'Beirne, Sarah L; Walsh, Sinead M; Fabre, Aurélie; Reviriego, Carlota; Worrell, Julie C; Counihan, Ian P; Lumsden, Robert V; Cramton-Barnes, Jennifer; Belperio, John A; Donnelly, Seamas C; Boylan, Denise; Marchal-Sommé, Joëlle; Kane, Rosemary; Keane, Michael P

    2015-09-15

    Epithelial to mesenchymal cell transition (EMT), whereby fully differentiated epithelial cells transition to a mesenchymal phenotype, has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). CXCR3 and its ligands are recognized to play a protective role in pulmonary fibrosis. In this study, we investigated the presence and extent of EMT and CXCR3 expression in human IPF surgical lung biopsies and assessed whether CXCR3 and its ligand CXCL9 modulate EMT in alveolar epithelial cells. Coexpression of the epithelial marker thyroid transcription factor-1 and the mesenchymal marker α-smooth muscle actin and CXCR3 expression was examined by immunohistochemical staining of IPF surgical lung biopsies. Epithelial and mesenchymal marker expression was examined by quantitative real-time PCR, Western blotting, and immunofluorescence in human alveolar epithelial (A549) cells treated with TGF-β1 and CXCL9, with Smad2, Smad3, and Smad7 expression and cellular localization examined by Western blotting. We found that significantly more cells were undergoing EMT in fibrotic versus normal areas of lung in IPF surgical lung biopsy samples. CXCR3 was expressed by type II pneumocytes and fibroblasts in fibrotic areas in close proximity to cells undergoing EMT. In vitro, CXCL9 abrogated TGF-β1-induced EMT. A decrease in TGF-β1-induced phosphorylation of Smad2 and Smad3 occurred with CXCL9 treatment. This was associated with increased shuttling of Smad7 from the nucleus to the cytoplasm where it inhibits Smad phosphorylation. This suggests a role for EMT in the pathogenesis of IPF and provides a novel mechanism for the inhibitory effects of CXCL9 on TGF-β1-induced EMT. Copyright © 2015 by The American Association of Immunologists, Inc.

  9. The transfection of BDNF to dopamine neurons potentiates the effect of dopamine D3 receptor agonist recovering the striatal innervation, dendritic spines and motor behavior in an aged rat model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Luis F Razgado-Hernandez

    Full Text Available The progressive degeneration of the dopamine neurons of the pars compacta of substantia nigra and the consequent loss of the dopamine innervation of the striatum leads to the impairment of motor behavior in Parkinson's disease. Accordingly, an efficient therapy of the disease should protect and regenerate the dopamine neurons of the substantia nigra and the dopamine innervation of the striatum. Nigral neurons express Brain Derived Neurotropic Factor (BDNF and dopamine D3 receptors, both of which protect the dopamine neurons. The chronic activation of dopamine D3 receptors by their agonists, in addition, restores, in part, the dopamine innervation of the striatum. Here we explored whether the over-expression of BDNF by dopamine neurons potentiates the effect of the activation of D3 receptors restoring nigrostriatal innervation. Twelve-month old Wistar rats were unilaterally injected with 6-hydroxydopamine into the striatum. Five months later, rats were treated with the D3 agonist 7-hydroxy-N,N-di-n-propy1-2-aminotetralin (7-OH-DPAT administered i.p. during 4½ months via osmotic pumps and the BDNF gene transfection into nigral cells using the neurotensin-polyplex nanovector (a non-viral transfection that selectively transfect the dopamine neurons via the high-affinity neurotensin receptor expressed by these neurons. Two months after the withdrawal of 7-OH-DPAT when rats were aged (24 months old, immunohistochemistry assays were made. The over-expression of BDNF in rats receiving the D3 agonist normalized gait and motor coordination; in addition, it eliminated the muscle rigidity produced by the loss of dopamine. The recovery of motor behavior was associated with the recovery of the nigral neurons, the dopamine innervation of the striatum and of the number of dendritic spines of the striatal neurons. Thus, the over-expression of BDNF in dopamine neurons associated with the chronic activation of the D3 receptors appears to be a promising strategy

  10. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression

    DEFF Research Database (Denmark)

    Cano, A; Pérez-Moreno, M A; Rodrigo, I

    2000-01-01

    The Snail family of transcription factors has previously been implicated in the differentiation of epithelial cells into mesenchymal cells (epithelial-mesenchymal transitions) during embryonic development. Epithelial-mesenchymal transitions are also determinants of the progression of carcinomas......, occurring concomitantly with the cellular acquisition of migratory properties following downregulation of expression of the adhesion protein E-cadherin. Here we show that mouse Snail is a strong repressor of transcription of the E-cadherin gene. Epithelial cells that ectopically express Snail adopt...

  11. Generalizing entanglement

    Science.gov (United States)

    Jia, Ding

    2017-12-01

    The expected indefinite causal structure in quantum gravity poses a challenge to the notion of entanglement: If two parties are in an indefinite causal relation of being causally connected and not, can they still be entangled? If so, how does one measure the amount of entanglement? We propose to generalize the notions of entanglement and entanglement measure to address these questions. Importantly, the generalization opens the path to study quantum entanglement of states, channels, networks, and processes with definite or indefinite causal structure in a unified fashion, e.g., we show that the entanglement distillation capacity of a state, the quantum communication capacity of a channel, and the entanglement generation capacity of a network or a process are different manifestations of one and the same entanglement measure.

  12. General topology

    CERN Document Server

    Willard, Stephen

    2004-01-01

    Among the best available reference introductions to general topology, this volume is appropriate for advanced undergraduate and beginning graduate students. Its treatment encompasses two broad areas of topology: ""continuous topology,"" represented by sections on convergence, compactness, metrization and complete metric spaces, uniform spaces, and function spaces; and ""geometric topology,"" covered by nine sections on connectivity properties, topological characterization theorems, and homotopy theory. Many standard spaces are introduced in the related problems that accompany each section (340

  13. Epithelial-microbial crosstalk in polymeric Ig receptor deficient mice

    NARCIS (Netherlands)

    Reikvam, D.H.; Derrien, M.M.N.; Islam, R.; Erofeev, A.; Grcic, V.; Sandvik, A.; Gaustad, P.; Meza-Zepeda, L.A.; Jahnsen, F.L.; Smidt, H.; Johansen, F.E.

    2012-01-01

    Innate and adaptive mucosal defense mechanisms ensure a homeostatic relationship with the large and complex mutualistic gut microbiota. Dimeric IgA and pentameric IgM are transported across the intestinal epithelium via the epithelial polymeric Ig receptor (pIgR) and provide a significant portion of

  14. [Stimulation of skin wound contraction and epithelialization by soluble collage].

    Science.gov (United States)

    Melikiants, A G; Kut'kova, O N

    1992-04-01

    It is found that local applications of the unguent with soluble collagen, but not solution of the collagen, stimulate healing of erosions and full-thickness excision wounds in the rat skin. Not all the stages of healing were stimulated, but only two of them--contraction and epithelialization.

  15. Membrane dynamics and the regulation of epithelial cell polarity

    NARCIS (Netherlands)

    van der Wouden, JM; Maier, O; van IJzendoorn, SCD; Hoekstra, D

    2003-01-01

    Plasma membranes of epithelial cells consist of two domains, an apical and a basolateral domain, the surfaces of which differ in composition. The separation of these domains by a tight junction and the fact that specific transport pathways exist for intracellular communication between these domains

  16. Suction blister lesions and epithelialization monitored by optical coherence tomography

    DEFF Research Database (Denmark)

    Ahlström, M G; Gjerdrum, L M R; Larsen, H F

    2018-01-01

    suction blister was raised on each buttock, and the blister roof was excised. Lesions were covered with moisture-retaining dressing. In Study 1, the lesions were OCT-scanned on day 0 (D0), D2 and D4 and excised for histological examination. In Study 2, the progress of epithelialization and skin barrier...

  17. Delayed Epithelial Closure After PRK Associated With Topical Besifloxacin Use.

    Science.gov (United States)

    Talamo, Jonathan H; Hatch, Kathryn M; Woodcock, Emily C

    2013-10-01

    To report the observation of prolonged reepithelialization after photorefractive keratectomy (PRK) associated with the use of besifloxacin 0.6% (Besivance; Bausch & Lomb, Rochester, NY) underneath bandage contact lenses (BCLs) placed during surgery. An office-based private practice and retrospective chart review. The healing parameters examined included epithelial healing time, haze formation, discomfort, and visual recovery of 4 patients (7 eyes) treated with besifloxacin 0.6% under BCLs placed after the PRK was performed. All the eyes had delayed epithelial closure (mean, 8.8 days; range 5-13 days). All the patients experienced a delayed visual recovery and significant pain after the surgery, and 2 of 4 patients experienced recurrent corneal erosions for weeks to months after they underwent the PRK. All but 1 eye developed corneal haze persisting for 1 year or more after the surgery. Only 1 eye among the 7 eyes treated with besifloxacin 0.6% under the BCL had 20/20 or better uncorrected visual acuity 3 months postoperatively. All the patients treated with besifloxacin 0.6% on the stromal bed exhibited significant problems with corneal epithelial healing and delayed visual recovery. We caution the use of besifloxacin 0.6% underneath a BCL during a PRK or other ocular surface surgeries requiring corneal epithelial debridement.

  18. Formation of reactive oxygen species in rat epithelial cells upon ...

    Indian Academy of Sciences (India)

    In our study, we investigated the influence of fly ash on the promotion of early inflammatory reactions like the formation of reactive oxygen species (ROS) in rat lung epithelial cells (RLE-6TN). Furthermore, we determined the formation of nitric oxide (NO). The cells show a clear dose-response relationship concerning the ...

  19. Arteriovenous shunt graft ulceration with sinus and graft epithelialization

    Directory of Open Access Journals (Sweden)

    Pooja Singhal

    2015-03-01

    Full Text Available Arteriovenous fistula and grafts are used as access sites for patients with chronic kidney disease and are prone for complications. Stent grafts are used to treat access site complications. We report a rare and unusual finding of epithelialization of the sinus tract and the lumen of a polytetrafluoroethylene graft, following ulceration of the overlying skin.

  20. Epithelial cell detachment by Porphyromonas gingivalis biofilm and planktonic cultures

    NARCIS (Netherlands)

    Huang, L.; van Loveren, C.; Ling, J.; Wei, X.; Crielaard, W.; Deng, D.M.

    2016-01-01

    Porphyromonas gingivalis is present as a biofilm at the sites of periodontal infections. The detachment of gingival epithelial cells induced by P. gingivalis biofilms was examined using planktonic cultures as a comparison. Exponentially grown planktonic cultures or 40-h biofilms were co-incubated

  1. Abdominal wall reconstruction using De-epithelialized dermal flap: A ...

    African Journals Online (AJOL)

    Abdominal wall reconstruction using De-epithelialized dermal flap: A new technique. ... Journal of Surgical Technique and Case Report ... Background: Although autogenous materials have been used in abdominal wall hernioplasty for a long time, the introduction of prosthetic materials diminished their popularity. However ...

  2. Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

    Söletormos, Georg; Duffy, Michael J; Othman Abu Hassan, Suher

    2016-01-01

    OBJECTIVE: To present an update of the European Group on Tumor Markers guidelines for serum markers in epithelial ovarian cancer. METHODS: Systematic literature survey from 2008 to 2013. The articles were evaluated by level of evidence and strength of recommendation. RESULTS: Because of its low s...

  3. Sphingolipid trafficking and protein sorting in epithelial cells

    NARCIS (Netherlands)

    Slimane, TA; Hoekstra, D

    2002-01-01

    Sphingolipids represent a minor, but highly dynamic subclass of lipids in all eukaryotic cells. They are involved in functions that range from structural protection to signal transduction and protein sorting, and participate in lipid raft assembly. In polarized epithelial cells, which display an

  4. Solid and papillary epithelial tumor of the pancreas

    International Nuclear Information System (INIS)

    Vega, Alejandro de la; Eyheremendy, Eduardo; Mondello, Eduardo; Florenzano, Nestor

    2001-01-01

    We report a case of a teenage female patient who presented upper abdominal pain and bilious vomiting. Laboratory analysis, abdominal ultrasound and contrast enhanced CT was performed. On the bases of these results she underwent a corporocaudal pancreatectomy. Pathology studied with immunohistochemical test, showed a solid and papillary epithelial neoplasm of the pancreas, which is an unusual disease. (author)

  5. Subtotal ablation of parietal epithelial cells induces crescent formation.

    NARCIS (Netherlands)

    Sicking, E.M.; Fuss, A.; Uhlig, S.; Jirak, P.; Dijkman, H.; Wetzels, J.; Engel, D.R.; Urzynicok, T.; Heidenreich, S.; Kriz, W.; Kurts, C.; Ostendorf, T.; Floege, J.; Smeets, B.; Moeller, M.J.

    2012-01-01

    Parietal epithelial cells (PECs) of the renal glomerulus contribute to the formation of both cellular crescents in rapidly progressive GN and sclerotic lesions in FSGS. Subtotal transgenic ablation of podocytes induces FSGS but the effect of specific ablation of PECs is unknown. Here, we established

  6. Parietal epithelial cells and podocytes in glomerular diseases

    NARCIS (Netherlands)

    Smeets, B.; Moeller, M.J.

    2012-01-01

    In recent years, it has become apparent that parietal epithelial cells (PECs) play an important role within the renal glomerulus, in particular in diseased conditions. In this review, we examine current knowledge about the role of PECs and their interactions with podocytes in development and under

  7. Abdominal wall reconstruction using De-epithelialized dermal flap: A ...

    African Journals Online (AJOL)

    Background: Although autogenous materials have been used in abdominal wall hernioplasty for a long time, the introduction of prosthetic materials diminished their popularity. However, these materials may be expensive, inappropriate or unavailable. The aim of this study is to determine the place of de-epithelialized dermal ...

  8. Erythropoietin protects the retinal pigment epithelial barrier against ...

    African Journals Online (AJOL)

    O2-induced hyperpermeability. H Zhang, Y Gong, X Wu, Y Shi, L Yin, Y Qiu. Abstract. Erythropoietin (EPO) is not limited to hematopoiesis; it may act as a protective cytokine. In this study, the retinal pigment epithelial (RPE) cell viability, cell ...

  9. Metabolic cooperativity between epithelial cells and adipocytes of mice

    International Nuclear Information System (INIS)

    Bartley, J.C.; Emerman, J.T.; Bissell, M.J.

    1981-01-01

    We have demonstrated that glycogen and lipid synthesis in adipocytes is modulated by the lactational state and that this modulation in mammary adipocytes requires the presence of the adjacent epithelial cells. Glycogen and lipid synthesis from [ 14 C]glucose was measured in mammary fat pads cleared of epithelium, in abdominal fat pads, and in adipocytes from both sources and from intact mammary gland of mature virgin, pregnant, and lactating mice. Accumulation of glycogen, the activity of glycogen synthase, and the lipogenic rate in abdominal and mammary adipocytes remained high during pregnancy but decreased to insignificant levels by early lactation. The depressant effects of lactation were observed solely in those mammary adipocytes isolated from intact glands. The presence of mammary epithelial cells was also required to effect the stimulated lipogenesis in mammary adipocytes during pregnancy. We conclude that the metabolic activity of adipocytes is modulated both during pregnancy and lactation to channel nutrients to the mammary epithelial cell. The fact that the changes occur in mammary adipocytes only when epithelial cells are present indicates that local as well as systemic factors are operating in these modulations

  10. Comparative proteome analysis of human epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Gagné Jean-Philippe

    2007-09-01

    Full Text Available Abstract Background Epithelial ovarian cancer is a devastating disease associated with low survival prognosis mainly because of the lack of early detection markers and the asymptomatic nature of the cancer until late stage. Using two complementary proteomics approaches, a differential protein expression profile was carried out between low and highly transformed epithelial ovarian cancer cell lines which realistically mimic the phenotypic changes observed during evolution of a tumour metastasis. This investigation was aimed at a better understanding of the molecular mechanisms underlying differentiation, proliferation and neoplastic progression of ovarian cancer. Results The quantitative profiling of epithelial ovarian cancer model cell lines TOV-81D and TOV-112D generated using iTRAQ analysis and two-dimensional electrophoresis coupled to liquid chromatography tandem mass spectrometry revealed some proteins with altered expression levels. Several of these proteins have been the object of interest in cancer research but others were unrecognized as differentially expressed in a context of ovarian cancer. Among these, series of proteins involved in transcriptional activity, cellular metabolism, cell adhesion or motility and cytoskeleton organization were identified, suggesting their possible role in the emergence of oncogenic pathways leading to aggressive cellular behavior. Conclusion The differential protein expression profile generated by the two proteomics approaches combined to complementary characterizations studies will open the way to more exhaustive and systematic representation of the disease and will provide valuable information that may be helpful to uncover the molecular mechanisms related to epithelial ovarian cancer.

  11. The disruption of the epithelial mesenchymal trophic unit in COPD.

    Science.gov (United States)

    Behzad, Ali R; McDonough, John E; Seyednejad, Nazgol; Hogg, James C; Walker, David C

    2009-12-01

    Progression of COPD is associated with a measurable increase in small airway wall thickness resulting from a repair and remodeling process that involves fibroblasts of the epithelial mesenchymal trophic unit (EMTU). The present study was designed to examine the organization of fibroblasts within the lamina propria of small airways with respect to their contacts with the epithelium and with each other in persons with COPD. Transmission electron microcopy (TEM) and three-dimensional (3D) reconstructions of serial TEM sections were used to estimate the frequency and determine the nature of the contacts between the epithelium and fibroblasts within the EMTU in small airways from 5 controls (smokers with normal lung function), from 6 persons with mild (GOLD-1) and 5 with moderate (GOLD-2) COPD. In airways from control lungs fibroblasts make frequent contact with cytoplasmic extensions of epithelial cells through apertures in the epithelial basal lamina, but the frequency of these fibroblast-epithelial contacts is reduced in both mild and moderate COPD compared to controls (p < 0.01). The 3D reconstructions showed that the cytoplasmic extensions of lamina propria fibroblasts form a reticulum with fibroblast-fibroblast contacts in an airway from a control subject but this reticulum may be reorganized in airways of COPD patients. Development of COPD is associated with significant disruption of the EMTU due to a reduction of contacts between fibroblasts and the epithelium.

  12. Molecular basis of potassium channels in pancreatic duct epithelial cells

    DEFF Research Database (Denmark)

    Hayashi, M.; Novak, Ivana

    2013-01-01

    Potassium channels regulate excitability, epithelial ion transport, proliferation, and apoptosis. In pancreatic ducts, K channels hyperpolarize the membrane potential and provide the driving force for anion secretion. This review focuses on the molecular candidates of functional K channels...... and pancreatic pathologies, including pancreatitis, cystic fibrosis, and cancer, in which the dysregulation or altered expression of K channels may be of importance....

  13. Epithelial-mesenchymal transition is associated with increased ...

    African Journals Online (AJOL)

    Yomi

    2011-12-16

    Dec 16, 2011 ... Key words: SMMC-7721, cancer stem cells, side population cells, invasion, epithelial-mesenchymal transition. INTRODUCTION. Invasion and metastasis are the most important biological ..... the metastatic phenotype of pancreatic cancer cells with- ... occludens-1 (ZO-1), and gain mesenchymal molecular.

  14. Parietal