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Articles 751 - 780 of 808

Full-Text Articles in Medical Neurobiology

Retroviral Vector And Cell-Based Assay For Measuring The Mutation Rate Of Retroviruses Employing Same, Dawn P. Wooley, Kelly Jo Huang Feb 2007

Retroviral Vector And Cell-Based Assay For Measuring The Mutation Rate Of Retroviruses Employing Same, Dawn P. Wooley, Kelly Jo Huang

Neuroscience, Cell Biology & Physiology Faculty Publications

Lentiviral-based retrovirus vectors and an in vivo mutation rate assay employing them. More particularly, an assay for directly determining the in vivo mutation rate of HIV-1.


Is Gene Therapy A Good Therapeutic Approach For Hiv-Positive Patients?, Jai G. Marathe, Dawn P. Wooley Feb 2007

Is Gene Therapy A Good Therapeutic Approach For Hiv-Positive Patients?, Jai G. Marathe, Dawn P. Wooley

Neuroscience, Cell Biology & Physiology Faculty Publications

Despite advances and options available in gene therapy for HIV-1 infection, its application in the clinical setting has been challenging. Although published data from HIV-1 clinical trials show safety and proof of principle for gene therapy, positive clinical outcomes for infected patients have yet to be demonstrated. The cause for this slow progress may arise from the fact that HIV is a complex multi-organ system infection. There is uncertainty regarding the types of cells to target by gene therapy and there are issues regarding insufficient transduction of cells and long-term expression. This paper discusses state-of-the-art molecular approaches against HIV-1 and …


Soluble Amyloid Oligomers Increase Bilayer Conductance By Altering Dielectric Structure, Yuri Sokolov, J. Ashot Kozak, Rakez Kayed, Alexandr Chanturiya, Charles G. Glabe, James E. Hall Nov 2006

Soluble Amyloid Oligomers Increase Bilayer Conductance By Altering Dielectric Structure, Yuri Sokolov, J. Ashot Kozak, Rakez Kayed, Alexandr Chanturiya, Charles G. Glabe, James E. Hall

Neuroscience, Cell Biology & Physiology Faculty Publications

The amyloid hypothesis of Alzheimer's toxicity has undergone a resurgence with increasing evidence that it is not amyloid fibrils but a smaller oligomeric species that produces the deleterious results. In this paper we address the mechanism of this toxicity. Only oligomers increase the conductance of lipid bilayers and patch-clamped mammalian cells, producing almost identical current-voltage curves in both preparations. Oligomers increase the conductance of the bare bilayer, the cation conductance induced by nonactin, and the anion conductance induced by tetraphenyl borate. Negative charge reduces the sensitivity of the membrane to amyloid, but cholesterol has little effect. In contrast, the area …


Unlv Magazine, Cate Weeks, Shane Bevell, Erin O'Donnell, Eric Leake, Lori Bachand, David G. Schwartz, David Ashley Oct 2006

Unlv Magazine, Cate Weeks, Shane Bevell, Erin O'Donnell, Eric Leake, Lori Bachand, David G. Schwartz, David Ashley

UNLV Magazine

No abstract provided.


Locus Ceruleus Regulates Sensory Encoding By Neurons And Networks In Waking Animals, David M. Devilbiss, Michelle E. Page, Barry D. Waterhouse Sep 2006

Locus Ceruleus Regulates Sensory Encoding By Neurons And Networks In Waking Animals, David M. Devilbiss, Michelle E. Page, Barry D. Waterhouse

Department of Neurosurgery Faculty Papers

Substantial evidence indicates that the locus ceruleus (LC)–norepinephrine (NE) projection system regulates behavioral state and state-dependent processing of sensory information. Tonic LC discharge (0.1–5.0 Hz) is correlated with levels of arousal and demonstrates an optimal firing rate during good performance in a sustained attention task. In addition, studies have shown that locally applied NE or LC stimulation can modulate the responsiveness of neurons, including those in the thalamus, to nonmonoaminergic synaptic inputs. Many recent investigations further indicate that within sensory relay circuits of the thalamus both general and specific features of sensory information are represented within the collective firing patterns …


Combining An Autologous Peripheral Nervous System “Bridge” And Matrix Modification By Chondroitinase Allows Robust, Functional Regeneration Beyond A Hemisection Lesion Of The Adult Rat Spinal Cord, John D. Houle, Veronica J. Tom, Debra A. Mayes, Gail Wagoner, Napoleon Phillips, Jerry Silver Jul 2006

Combining An Autologous Peripheral Nervous System “Bridge” And Matrix Modification By Chondroitinase Allows Robust, Functional Regeneration Beyond A Hemisection Lesion Of The Adult Rat Spinal Cord, John D. Houle, Veronica J. Tom, Debra A. Mayes, Gail Wagoner, Napoleon Phillips, Jerry Silver

Neuroscience, Cell Biology & Physiology Faculty Publications

Chondroitinase-ABC (ChABC) was applied to a cervical level 5 (C5) dorsal quadrant aspiration cavity of the adult rat spinal cord to degrade the local accumulation of inhibitory chondroitin sulfate proteoglycans. The intent was to enhance the extension of regenerated axons from the distal end of a peripheral nerve (PN) graft back into the C5 spinal cord, having bypassed a hemisection lesion at C3. ChABC-treated rats showed (1) gradual improvement in the range of forelimb swing during locomotion, with some animals progressing to the point of raising their forelimb above the nose, (2) an enhanced ability to use the forelimb in …


Heme Deficiency In Alzheimer's Disease: A Possible Connection To Porphyria, Barney E. Dwyer, Meghan L. Stone, Xiongwei Zhu, George Perry, Mark A. Smith Apr 2006

Heme Deficiency In Alzheimer's Disease: A Possible Connection To Porphyria, Barney E. Dwyer, Meghan L. Stone, Xiongwei Zhu, George Perry, Mark A. Smith

Dartmouth Scholarship

Mechanisms that cause Alzheimer's disease (AD), an invariably fatal neurodegenerative disease, are unknown. Important recent data indicate that neuronal heme deficiency may contribute to AD pathogenesis. If true, factors that contribute to the intracellular heme deficiency could potentially alter the course of AD. The porphyrias are metabolic disorders characterized by enzyme deficiencies in the heme biosynthetic pathway. We hypothesize that AD may differ significantly in individuals possessing the genetic trait for an acute hepatic porphyria. We elaborate on this hypothesis and briefly review the characteristics of the acute hepatic porphyrias that may be relevant to AD. We note the proximity …


Pro-Opiomelanocortin Co-Localizes With Corticotropin-Releasing Factor In Axon Terminals Of The Noradrenergic Nucleus Locus Coeruleus, Beverly A.S. Reyes, Julia D. Glaser, Ronaldo Magtoto, Elisabeth K. Van Bockstaele Apr 2006

Pro-Opiomelanocortin Co-Localizes With Corticotropin-Releasing Factor In Axon Terminals Of The Noradrenergic Nucleus Locus Coeruleus, Beverly A.S. Reyes, Julia D. Glaser, Ronaldo Magtoto, Elisabeth K. Van Bockstaele

Department of Neurosurgery Faculty Papers

We previously demonstrated that the opioid peptide, enkephalin, and corticotropin-releasing factor (CRF) are occasionally co-localized in individual axon terminals but more frequently converge on common dendrites in the locus coeruleus (LC). To further examine potential opioid co-transmitters in CRF afferents, we investigated the distribution of proopiomelanocortin (POMC), the precursor that yields the potent bioactive peptide, ß-endorphin, with respect to CRF immunoreactivity using immunofluorescence and immunoelectron microscopic analyses of the LC. Coronal sections were collected through the dorsal pontine tegmentum of rat brain and processed for immunocytochemical detection of POMC and CRF or tyrosine hydroxylase (TH). POMC-immunoreactive processes exhibited a distinct …


Dopamine-D1 And Δ-Opioid Receptors Co-Exist In Rat Striatal Neurons, L. M. Ambrose-Lanci, S. M. Gallagher, E. M. Unterwald, E. J. Van Bockstaele Feb 2006

Dopamine-D1 And Δ-Opioid Receptors Co-Exist In Rat Striatal Neurons, L. M. Ambrose-Lanci, S. M. Gallagher, E. M. Unterwald, E. J. Van Bockstaele

Department of Neurosurgery Faculty Papers

Cocaine’s enhancement of dopaminergic neurotransmission in the mesolimbic pathway plays a critical role in the initial reinforcing properties of this drug. However, other neurotransmitter systems are also integral to the addiction process. A large body of data indicates that opioids and dopamine together mediate emotional and reinforced behaviors. In support of this, cocaine-mediated increases in activation of dopamine D1 receptors (D1R) results in a desensitization of δ-opioid receptor (DOR) signaling through adenylyl cyclase (AC) in striatal neurons. To further define cellular mechanisms underlying this effect, the subcellular distribution of DOR and D1R was examined in the rat dorsolateral striatum. Dual …


Mechanisms Of Hbo-Induced Neuroprotection In A Neonatal Hypoxia-Ischemia Model, John Winter Calvert Dec 2005

Mechanisms Of Hbo-Induced Neuroprotection In A Neonatal Hypoxia-Ischemia Model, John Winter Calvert

Loma Linda University Electronic Theses, Dissertations & Projects

With an incidence approaching 1/4000 live births and as high as 60% in low birth weight infants, cerebral hypoxia-ischemia during the perinatal period is the single most important cause of acute mortality and chronic disability in newborns. Herein, we tested the hypothesis that following a hypoxic-ischemic insult hyperbaric oxygen (HBO) treatment can restore high energy metabolite levels in the affected regions of the brain and through this increase in energy levels ameliorate the spread of cell death following the insult. We also investigated if an additional mechanism by which HBO affords its neuroprotection is by altering the expression of the …


Charge Screening By Internal Ph And Polyvalent Cations As A Mechanism For Activation, Inhibition, And Rundown Of Trpm7/Mic Channels, J. Ashot Kozak, Masayuki Matsushita, Angus C. Nairn, Michael D. Cahalan Nov 2005

Charge Screening By Internal Ph And Polyvalent Cations As A Mechanism For Activation, Inhibition, And Rundown Of Trpm7/Mic Channels, J. Ashot Kozak, Masayuki Matsushita, Angus C. Nairn, Michael D. Cahalan

Neuroscience, Cell Biology & Physiology Faculty Publications

The Mg2+-inhibited cation (MIC) current, believed to represent activity of TRPM7 channels, is found in lymphocytes and mast cells, cardiac and smooth muscle, and several other eukaryotic cell types. MIC current is activated during whole-cell dialysis with divalent-free internal solutions. Millimolar concentrations of intracellular Mg2+ (or other divalent metal cations) inhibit the channels in a voltage-independent manner. The nature of divalent inhibition and the mechanism of channel activation in an intact cell remain unknown. We show that the polyamines (spermine, spermidine, and putrescine) inhibit the MIC current, also in a voltage-independent manner, with a potency that parallels …


Resting Potential–Dependent Regulation Of The Voltage Sensitivity Of Sodium Channel Gating In Rat Skeletal Muscle In Vivo, Gregory N. Filatov, Martin J. Pinter, Mark M. Rich Aug 2005

Resting Potential–Dependent Regulation Of The Voltage Sensitivity Of Sodium Channel Gating In Rat Skeletal Muscle In Vivo, Gregory N. Filatov, Martin J. Pinter, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Normal muscle has a resting potential of −85 mV, but in a number of situations there is depolarization of the resting potential that alters excitability. To better understand the effect of resting potential on muscle excitability we attempted to accurately simulate excitability at both normal and depolarized resting potentials. To accurately simulate excitability we found that it was necessary to include a resting potential–dependent shift in the voltage dependence of sodium channel activation and fast inactivation. We recorded sodium currents from muscle fibers in vivo and found that prolonged changes in holding potential cause shifts in the voltage dependence of …


Stim1, An Essential And Conserved Component Of Store-Operated Ca2+ Channel Function, Jack Roos, Paul J. Digregorio, Andriy V. Yeromin, Kari Ohlsen, Maria I. Lioudyno, Shenyuan L. Zhang, Olga Safrina, J. Ashot Kozak, Steven L. Wagner, Michael D. Cahalan, Gönül Veliçelebi, Kenneth A. Stauderman May 2005

Stim1, An Essential And Conserved Component Of Store-Operated Ca2+ Channel Function, Jack Roos, Paul J. Digregorio, Andriy V. Yeromin, Kari Ohlsen, Maria I. Lioudyno, Shenyuan L. Zhang, Olga Safrina, J. Ashot Kozak, Steven L. Wagner, Michael D. Cahalan, Gönül Veliçelebi, Kenneth A. Stauderman

Neuroscience, Cell Biology & Physiology Faculty Publications

Store-operated Ca2+ (SOC) channels regulate many cellular processes, but the underlying molecular components are not well defined. Using an RNA interference (RNAi)-based screen to identify genes that alter thapsigargin (TG)-dependent Ca2+ entry, we discovered a required and conserved role of Stim in SOC influx. RNAi-mediated knockdown of Stim in Drosophila S2 cells significantly reduced TG-dependent Ca2+ entry. Patch-clamp recording revealed nearly complete suppression of the Drosophila Ca2+ release-activated Ca2+(CRAC) current that has biophysical characteristics similar to CRAC current in human T cells. Similarly, knockdown of the human homologue STIM1 significantly reduced CRAC channel activity …


A Developmental Switch In The Response Of Drg Neurons To Ets Transcription Factor Signaling, Simon Hippenmeyer, Eline Vrieseling, Markus Sigrist, Thomas Portmann, Celia Laengle, David R. Ladle, Silvia Arber May 2005

A Developmental Switch In The Response Of Drg Neurons To Ets Transcription Factor Signaling, Simon Hippenmeyer, Eline Vrieseling, Markus Sigrist, Thomas Portmann, Celia Laengle, David R. Ladle, Silvia Arber

Neuroscience, Cell Biology & Physiology Faculty Publications

Two ETS transcription factors of the Pea3 subfamily are induced in subpopulations of dorsal root ganglion (DRG) sensory and spinal motor neurons by target-derived factors. Their expression controls late aspects of neuronal differentiation such as target invasion and branching. Here, we show that the late onset of ETS gene expression is an essential requirement for normal sensory neuron differentiation. We provide genetic evidence in the mouse that precocious ETS expression in DRG sensory neurons perturbs axonal projections, the acquisition of terminal differentiation markers, and their dependence on neurotrophic support. Together, our findings indicate that DRG sensory neurons exhibit a temporal …


The Cns Role Of Toll-Like Receptor 4 In Innate Neuroimmunity And Painful Neuropathy, Flobert Y. Tanga, Nancy Nutile-Mcmenemy, Joyce A. Deleo Apr 2005

The Cns Role Of Toll-Like Receptor 4 In Innate Neuroimmunity And Painful Neuropathy, Flobert Y. Tanga, Nancy Nutile-Mcmenemy, Joyce A. Deleo

Dartmouth Scholarship

Neuropathic pain remains a prevalent and persistent clinical problem because of our incomplete understanding of its pathogenesis. This study demonstrates for the first time, to our knowledge, a critical role for CNS innate immunity by means of microglial Toll-like receptor 4 (TLR4) in the induction phase of behavioral hypersensitivity in a mouse and rat model of neuropathy. We hypothesized that after L5 nerve transection, CNS neuroimmune activation and subsequent cytokine expression are triggered by the stimulation of microglial membrane-bound TLR4. To test this hypothesis, experiments were undertaken to assess tactile and thermal hypersensitivity in genetically altered (i.e., TLR4 knockout and …


Role For Akt3/Protein Kinase Bγ In Attainment Of Normal Brain Size, Rachel M. Easton, Han Cho, Kristin Roovers, Diana W. Shineman Mar 2005

Role For Akt3/Protein Kinase Bγ In Attainment Of Normal Brain Size, Rachel M. Easton, Han Cho, Kristin Roovers, Diana W. Shineman

Dartmouth Scholarship

Studies of Drosophila and mammals have revealed the importance of insulin signaling through phosphatidylinositol 3-kinase and the serine/threonine kinase Akt/protein kinase B for the regulation of cell, organ, and organismal growth. In mammals, three highly conserved proteins, Akt1, Akt2, and Akt3, comprise the Akt family, of which the first two are required for normal growth and metabolism, respectively. Here we address the function of Akt3. Like Akt1, Akt3 is not required for the maintenance of normal carbohydrate metabolism but is essential for the attainment of normal organ size. However, in contrast to Akt1/ mice, which display a …


Myelin Proteolipid Protein-Specific Cd4+ Cd25+ Regulatory Cells Mediate Genetic Resistance To Experimental Autoimmune Encephalomyelitis, Jay Reddy, Zsolt Illés, Xingmin Zhang, Jeffrey Encinas, Jason Pyrdol, Lindsay Nicholson, Raymond A. Sobel, Kai W. Wucherpfennig, Vijay K. Kuchroo, James P. Allison Oct 2004

Myelin Proteolipid Protein-Specific Cd4+ Cd25+ Regulatory Cells Mediate Genetic Resistance To Experimental Autoimmune Encephalomyelitis, Jay Reddy, Zsolt Illés, Xingmin Zhang, Jeffrey Encinas, Jason Pyrdol, Lindsay Nicholson, Raymond A. Sobel, Kai W. Wucherpfennig, Vijay K. Kuchroo, James P. Allison

Jay Reddy Publications

SJL mice are highly susceptible to experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) peptide 139–151, whereas H-2 congenic B10.S mice are resistant. Immunodominance and susceptibility to EAE are associated with a high precursor frequency of PLP 139–151-specific T cells in the naive repertoire of SJL mice. To understand the mechanism of EAE resistance in B10.S mice, we determined the precursor frequency of PLP 139–151-reactive T cells in both strains by using IAs/PLP 139–151 tetramers. SJL and B10.S mice had similar frequencies of tetramer-reactive T cells in the naive peripheral repertoire. However, in SJL mice, the …


Modified Amino Acid Copolymers Suppress Myelin Basic Protein 85–99-Induced Encephalomyelitis In Humanized Mice Through Different Effects On T Cells, Zsolt Illés, Joel N.H. Stern, Jay Reddy, Hanspeter Waldner, Marcin P. Mycko, Celia F. Brosnan, Stephan Ellmerich, Daniel M. Altmann, Laura Santambrogio, Jack L. Strominger, Vijay K. Kuchroo Aug 2004

Modified Amino Acid Copolymers Suppress Myelin Basic Protein 85–99-Induced Encephalomyelitis In Humanized Mice Through Different Effects On T Cells, Zsolt Illés, Joel N.H. Stern, Jay Reddy, Hanspeter Waldner, Marcin P. Mycko, Celia F. Brosnan, Stephan Ellmerich, Daniel M. Altmann, Laura Santambrogio, Jack L. Strominger, Vijay K. Kuchroo

Jay Reddy Publications

A humanized mouse bearing the HLA-DR2 (DRA/DRB1*1501) pro- tein associated with multiple sclerosis (MS) and the myelin basic protein (MBP) 85–99-specific HLA-DR2-restricted T cell receptor from an MS patient has been used to examine the effectiveness of modified amino acid copolymers poly(F,Y,A,K)n and poly- (V,W,A,K)n in therapy of MBP 85–99-induced experimental auto-immune encephalomyelitis (EAE) in comparison to Copolymer 1 [Copaxone, poly(Y,E,A,K)n]. The copolymers were designed to optimize binding to HLA-DR2. Vaccination, prevention, and treatment of MBP-induced EAE in the humanized mice with copolymers FYAK and VWAK ameliorated EAE more effectively than Copolymer 1, reduced the number of pathological lesions, and …


Analysis Of Expression Patterns Of Scl And Pax7 In The Mouse Brain For Potential Concomitant Function Within The Mesencephalon, Julie Stampalia Jan 2004

Analysis Of Expression Patterns Of Scl And Pax7 In The Mouse Brain For Potential Concomitant Function Within The Mesencephalon, Julie Stampalia

Theses : Honours

Investigation of the cascade of events that leads to brain formation during embryogenesis allows an understanding of the processes involved that may well be applicable to future neurodegenerative therapies. Two genes at work during embryonic neurogenesis in a brain region called the superior colliculus are Scl, a member of the basic helix-loop-helix factor transcription factor family and Pax7, a paired box transcription factor containing a homeobox dornain. The superior coiliculus forms part of the visual system in mammals and in sepmate studies both the Scl and Pax7 genes have been shown to be present in this region of the mouse …


Effect Of Background Synaptic Activity On Excitatory-Postsynaptic Potential-Spike Coupling, Veronika Zsiros Dec 2003

Effect Of Background Synaptic Activity On Excitatory-Postsynaptic Potential-Spike Coupling, Veronika Zsiros

Theses and Dissertations (ETD)

Neurons receive large amount of synaptic inputs in vivo, which may impact the coupling between EPSPs and spikes. We mimicked the in vivo synaptic activity of the cell with the dynamic clamp system. We recorded from pyramidal cells in neocortical slices in vitro to investigate how timing and probability of spike generation in response to an EPSP is affected by background synaptic conductance under these conditions. We found that near threshold, background synaptic conductance improved the precision of spike timing by reducing the depolarization-related prolongation of the EPSP. In cells with ongoing spike activity and background synaptic conductances, an …


Validation Of A Serotonin Checklist In A Parkinson’S Disease Population, Kelly Diane Darby-Holder Sep 2003

Validation Of A Serotonin Checklist In A Parkinson’S Disease Population, Kelly Diane Darby-Holder

Loma Linda University Electronic Theses, Dissertations & Projects

Although the distinctive pathological marker of Parkinson’s Disease is the progressive death of neurons that produce dopamine, there are also alterations in the production of quantities of other neurotransmitters, such as norepinephrine and serotonin that contribute to the disease. Parkinson’s Disease (PD) can be divided into two distinct classes based on the manifestation of motor symptoms, Type A and Type B Parkinson’s Disease. Type B PD patients often manifest symptoms in which serotonin deficiency plays an important role, which often includes a history of depression. Within the brain and spinal cord serotonin has wide spread projections, acting as an important …


Distinct Properties Of Crac And Mic Channels In Rbl Cells, J. Ashot Kozak, Hubert H. Kerschbaum, Michael D. Cahalan Aug 2002

Distinct Properties Of Crac And Mic Channels In Rbl Cells, J. Ashot Kozak, Hubert H. Kerschbaum, Michael D. Cahalan

Neuroscience, Cell Biology & Physiology Faculty Publications

In rat basophilic leukemia (RBL) cells and Jurkat T cells, Ca2+ release–activated Ca2+ (CRAC) channels open in response to passive Ca2+ store depletion. Inwardly rectifying CRAC channels admit monovalent cations when external divalent ions are removed. Removal of internal Mg2+ exposes an outwardly rectifying current (Mg2+-inhibited cation [MIC]) that also admits monovalent cations when external divalent ions are removed. Here we demonstrate that CRAC and MIC currents are separable by ion selectivity and rectification properties: by kinetics of activation and susceptibility to run-down and by pharmacological sensitivity to external Mg2+, spermine, and …


Neuromotor And Cognitive Development In Children With Cerebral Palsy In Relation To Neural Plasticity, Vaniecea Pollard May 2001

Neuromotor And Cognitive Development In Children With Cerebral Palsy In Relation To Neural Plasticity, Vaniecea Pollard

McCabe Thesis Collection

Infants with neurological disabilities, such as cerebral palsy (CP) and Down syndrome (DS), show severe delays in motor and cognitive development relative to chronological age. Involvement of neural plasticity as a treatment of such neurological disorders is increasingly being seen. Previous studies have found that interventions involving sensory linked motor performance have been critical in facilitating motor improvement. The purpose of this study was to compare self-initiated mobility in children with CP and DS. Three infants, ages 8, 9, and 22 months, with diagnoses of no CP, DS, and CP respectively, participated in the study. The infants were videotaped in …


Single Channel Properties And Regulated Expression Of Ca2+ Release-Activated Ca2+ (Crac) Channels In Human T Cells, Alla F. Fomina, Christopher M. Fanger, J. Ashot Kozak, Michael D. Cahalan Sep 2000

Single Channel Properties And Regulated Expression Of Ca2+ Release-Activated Ca2+ (Crac) Channels In Human T Cells, Alla F. Fomina, Christopher M. Fanger, J. Ashot Kozak, Michael D. Cahalan

Neuroscience, Cell Biology & Physiology Faculty Publications

Although the crucial role of Ca2+ influx in lymphocyte activation has been well documented, little is known about the properties or expression levels of Ca2+ channels in normal human T lymphocytes. The use of Na+ as the permeant ion in divalent-free solution permitted Ca2+ release-activated Ca2+ (CRAC) channel activation, kinetic properties, and functional expression levels to be investigated with single channel resolution in resting and phytohemagglutinin (PHA)-activated human T cells. Passive Ca2+ store depletion resulted in the opening of 41-pS CRAC channels characterized by high open probabilities, voltage-dependent block by extracellular Ca2+ in …


Prolonged Cyclooxygenase-2 Induction In Neurons And Glia Following Traumatic Brain Injury In The Rat, Kenneth I. Strauss, Mary F. Barbe, Renee Marshall Demarest, Ramesh Raghupathi, Samir Mehta, Raj K. Narayan Aug 2000

Prolonged Cyclooxygenase-2 Induction In Neurons And Glia Following Traumatic Brain Injury In The Rat, Kenneth I. Strauss, Mary F. Barbe, Renee Marshall Demarest, Ramesh Raghupathi, Samir Mehta, Raj K. Narayan

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Cyclooxygenase-2 (COX2) is a primary inflammatory mediator that converts arachidonic acid into precursors of vasoactive prostaglandins, producing reactive oxygen species in the process. Under normal conditions COX2 is not detectable, except at low abundance in the brain. This study demonstrates a distinctive pattern of COX2 increases in the brain over time following traumatic brain injury (TBI). Quantitative lysate ribonuclease protection assays indicate acute and sustained increases in COX2 mRNA in two rat models of TBI. In the lateral fluid percussion model, COX2 mRNA is significantly elevated (>twofold, p < 0.05, Dunnett) at 1 day postinjury in the injured cortex and bilaterally in the hippocampus, compared to sham-injured controls. In the lateral cortical impact model (LCI), COX2 mRNA peaks around 6 h postinjury in the ipsilateral cerebral cortex (fivefold induction, p < 0.05, Dunnett) and in the ipsilateral and contralateral hippocampus (two- and six-fold induction, respectively, p < 0.05, Dunnett). Increases are sustained out to 3 days postinjury in the injured cortex in both models. Further analyses use the LCI model to evaluate COX2 induction. Immunoblot analyses confirm increased levels of COX2 protein in the cortex and hippocampus. Profound increases in COX2 protein are observed in the cortex at 1-3 days, that return to sham levels by 7 days postinjury (p < 0.05, Dunnett). The cellular pattern of COX2 induction following TBI has been characterized using immunohistochemistry. COX2-immunoreactivity (-ir) rises acutely (cell numbers and intensity) and remains elevated for several days following TBI. Increases in COX2-ir colocalize with neurons (MAP2-ir) and glia (GFAP-ir). Increases in COX2-ir are observed in cerebral cortex and hippocampus, ipsilateral and contralateral to injury as early as 2 h postinjury. Neurons in the ipsilateral parietal, perirhinal and piriform cortex become intensely COX2-ir from 2 h to at least 3 days postinjury. In agreement with the mRNA and immunoblot results, COX2-ir appears greatest in the contralateral hippocampus. Hippocampal COX2-ir progresses from the pyramidal cell layer of the CA1 and CA2 region at 2 h, to the CA3 pyramidal cells and dentate polymorphic and granule cell layers by 24 h postinjury. These increases are distinct from those observed following inflammatory challenge, and correspond to brain areas previously identified with the neurological and cognitive deficits associated with TBI. While COX2 induction following TBI may result in selective beneficial responses, chronic COX2 production may contribute to free radical mediated cellular damage, vascular dysfunction, and alterations in cellular metabolism. These may cause secondary injuries to the brain that promote neuropathology and worsen behavioral outcome.


Genetic Control Of Eye Development, A Case Study Focused On The Murine Mutation Belly Spot And Tail (Bst), Qing Tang Dec 1999

Genetic Control Of Eye Development, A Case Study Focused On The Murine Mutation Belly Spot And Tail (Bst), Qing Tang

Theses and Dissertations (ETD)

Development of the eye is controlled by a network of genes, often conserved, that regulate the timing and location of cellular differentiation. One approach to understanding this network of genes and their interaction is to focus on mutations, spontaneous or induced, that predictably disrupt the proper function of such networks, and by examining the effect of such disruption on the function of other genes.

The Belly spot and tail (Bst) semi-dominant mutation, mapped to mouse Chromosome 16, leads to developmental defects of the eye, skeleton, and coat pigmentation. In the eye, the mutant phenotype is characterized by the presence of …


Global Cns Gene Transfer For A Childhood Neurogenetic Enzyme Deficiency: Canavan Disease., Paola Leone, Christopher G Janson, Scott J Mcphee, Matthew J During Aug 1999

Global Cns Gene Transfer For A Childhood Neurogenetic Enzyme Deficiency: Canavan Disease., Paola Leone, Christopher G Janson, Scott J Mcphee, Matthew J During

Department of Neurosurgery Faculty Papers

The neurogenetic prototypic disease on which we chose to test our gene therapy strategy is Canavan disease (CD). CD is an autosomal recessive leukodystrophy associated with spongiform degeneration of the brain. At present the disease is uniformly fatal in affected probands. CD is characterized by mutations in the aspartoacylase (ASPA) gene, resulting in loss of enzyme activity. In this review, recent evidence is summarized on the etiology and possible treatments for CD. In particular, we discuss two gene delivery systems representing recent advances in both viral and liposome technology: a novel cationic liposome-polymer-DNA (LPD) complex, DCChol/DOPE-protamine, as well as recombinant …


Transgenic Mice Which Overexpress Neurotrophin-3 (Nt-3) And Method Of Use, Kathryn M. Albers, Brian M. Davis Jan 1999

Transgenic Mice Which Overexpress Neurotrophin-3 (Nt-3) And Method Of Use, Kathryn M. Albers, Brian M. Davis

Neuroscience Faculty Patents

Transgenic mice express increased levels of neurotrophin-3 (NT-3) in epithelium when their ancestors are microinjected with the NT-3 gene. The NT-3 growth factor expressing transgenic mice are useful in the study of neurodegenerative disorders of the brain such as Parkinson's syndrome and Alzheimer's disease, of the spinal cord motor neurons such as amyotrophic lateral sclerosis, and for testing drug candidates for the treatment of these diseases.


Staphylococcal Enterotoxin B Primes Cytokine Secretion And Lytic Activity In Response To Native Bacterial Antigens, K. M. Mason, T. D. Dryden, Nancy J. Bigley, P. S. Fink Nov 1998

Staphylococcal Enterotoxin B Primes Cytokine Secretion And Lytic Activity In Response To Native Bacterial Antigens, K. M. Mason, T. D. Dryden, Nancy J. Bigley, P. S. Fink

Neuroscience, Cell Biology & Physiology Faculty Publications

Superantigens stimulate T-lymphocyte proliferation and cytokine production, but the effects of superantigen exposure on cell function within a complex, highly regulated immune response remain to be determined. In this study, we demonstrate that superantigen exposure significantly alters the murine host response to bacterial antigens in an in vitro coculture system. Two days after exposure to the superantigen staphylococcal enterotoxin B, splenocytes cultured with Streptococcus mutans produced significantly greater amounts of gamma interferon (IFN-gamma) and interleukin-12 than did sham-injected controls. The majority of IFN-gamma production appeared to be CD8(+) T-cell derived since depletion of this cell type dramatically reduced the levels …


Identifying Swelling-Activated Channels From Ion Selectivity Patterns, Dan R. Halm Sep 1998

Identifying Swelling-Activated Channels From Ion Selectivity Patterns, Dan R. Halm

Neuroscience, Cell Biology & Physiology Faculty Publications

No abstract provided.