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Search Results: 1 - 10 of 340358 matches for " David J. Fink "
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HSV-mediated expression of interleukin-4 in dorsal root ganglion neurons reduces neuropathic pain
Shuanglin Hao, Marina Mata, Joseph C Glorioso, David J Fink
Molecular Pain , 2006, DOI: 10.1186/1744-8069-2-6
Abstract: Subcutaneous inoculation of S4IL4 in the foot transduced lumbar DRG to produce IL-4. Transgene-mediated expression of IL-4 did not alter thermal latency or tactile threshold in normal animals, but inoculation of S4IL4 1 week after spinal nerve ligation (SNL) reduced mechanical allodynia and reversed thermal hyperalgesia resulting from SNL. Inoculation of S4IL4 1 week before SNL delayed the development of thermal hyperalgesia and tactile allodynia, but did not prevent the ultimate development of these manifestations of neuropathic pain. S4IL4 inoculation suppressed non-noxious-induced expression of c-Fos immunoreactivity in dorsal horn of spinal cord and reversed the upregulation of spinal IL-1β, PGE2, and phosphorylated-p38 MAP kinase, characteristic of neuropathic pain.HSV-mediated expression of IL-4 effectively reduces the behavioral manifestations of neuropathic pain, and reverses some of the biochemical and histologic correlates of neuropathic pain at the spinal level.Neural-immune interactions play a key role in the pathogenesis of neuropathic pain. Partial nerve injury results in the release of proinflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha from activated Schwann cells, endothelial cells, and macrophages in nerve [1] to produce direct effects on nociceptive activity [2]. Peripheral nerve damage also activates microglia and astrocytes in spinal cord to release the same proinflammatory cytokines in dorsal horn [3-6], resulting in central sensitization [7,8] and an exaggerated pain response characteristic of neuropathic pain [9-11].IL-4 is a prototypical anti-inflammatory cytokine that modulates macrophage activity through global suppression of proinflammatory cytokines [12-14], in addition to pleiotropic effects on the development of immune cells and the immune response [15]. The broad spectrum of IL-4 action makes it an attractive candidate for suppressing cytokine activation in neuropathic pain, but the short half-life of
Two-Photon Compatibility and Single-Voxel, Single-Trial Detection of Subthreshold Neuronal Activity by a Two-Component Optical Voltage Sensor
Ann E. Fink, Kevin J. Bender, Laurence O. Trussell, Thomas S. Otis, David A. DiGregorio
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0041434
Abstract: Minimally invasive measurements of neuronal activity are essential for understanding how signal processing is performed by neuronal networks. While optical strategies for making such measurements hold great promise, optical sensors generally lack the speed and sensitivity necessary to record neuronal activity on a single-trial, single-neuron basis. Here we present additional biophysical characterization and practical improvements of a two-component optical voltage sensor (2cVoS), comprised of the neuronal tracer dye, DiO, and dipicrylamine (DiO/DPA). Using laser spot illumination we demonstrate that membrane potential-dependent fluorescence changes can be obtained in a wide variety of cell types within brain slices. We show a correlation between membrane labeling and the sensitivity of the magnitude of fluorescence signal, such that neurons with the brightest membrane labeling yield the largest ΔF/F values per action potential (AP; ~40%). By substituting a blue-shifted donor for DiO we confirm that DiO/DPA works, at least in part, via a F?rster resonance energy transfer (FRET) mechanism. We also describe a straightforward iontophoretic method for labeling multiple neurons with DiO and show that DiO/DPA is compatible with two-photon (2P) imaging. Finally, exploiting the high sensitivity of DiO/DPA, we demonstrate AP-induced fluorescence transients (fAPs) recorded from single spines of hippocampal pyramidal neurons and single-trial measurements of subthreshold synaptic inputs to granule cell dendrites. Our findings suggest that the 2cVoS, DiO/DPA, enables optical measurements of trial-to-trial voltage fluctuations with very high spatial and temporal resolution, properties well suited for monitoring electrical signals from multiple neurons within intact neuronal networks.
Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy
Munmun Chattopadhyay, Zhigang Zhou, Shuanglin Hao, Marina Mata, David J Fink
Molecular Pain , 2012, DOI: 10.1186/1744-8069-8-17
Abstract: Subcutaneous inoculation of the miRNA-expressing HSV vector into the feet of diabetic rats to transduce DRG resulted in a reduction in NaVα subunit levels in DRG neurons, coincident with a reduction in cold allodynia, thermal hyperalgesia and mechanical hyperalgesia.These data support the role of increased NaVα protein in DRG in the pathogenesis of pain in diabetic neuropathy, and provide a proof-of-principle demonstration for the development of a novel therapy that could be used to treat intractable pain in patients with diabetic neuropathy.Pain is a common complication of diabetic neuropathy that, despite substantial advances in understanding of pathophysiology, remains relatively refractory to treatment with available agents [1]. In rats with streptozotocin (STZ) induced diabetes and painful neuropathy, an increase in the alpha (pore-forming) subunit of voltage gated sodium channel isoform 1.7 (NaV1.7) in primary sensory afferent neurons of the dorsal root ganglia (DRG) has been reported [2], a change that correlates with increased amplitude and negative shift of the activation of tetrodotoxin (TTX)-sensitive current in those neurons. A potential pathogenic role for NaV1.7 in the development of pain in this syndrome is supported by the observation that gain of function mutations in NaV1.7 cause inherited spontaneous neuropathic pain syndromes primary erythermalgia [3,4] and paroxysmal extreme pain disorder [5].In previous studies we have constructed a series of herpes simplex virus (HSV)-based gene transfer vectors that effectively transduce DRG in vivo from skin inoculation, and have used these vectors to express inhibitory neurotransmitters [6-8] or neurotrophic factors [9-11]. In order to explicitly test the role of increased levels of NaV in DRG in the pathogenesis of pain in PDN, we constructed a non-replicating herpes simplex virus (HSV)-based vector to reduce NaVα protein in DRG, and compared the effect of NaVα subunit knockdown on pain-related behaviors i
Glial TNFα in the spinal cord regulates neuropathic pain induced by HIV gp120 application in rats
Wenwen Zheng, Handong Ouyang, Xuexing Zheng, Shue Liu, Marina Mata, David J Fink, Shuanglin Hao
Molecular Pain , 2011, DOI: 10.1186/1744-8069-7-40
Abstract: Peripheral gp120 application into the rat sciatic nerve induced mechanical allodynia for more than 7 weeks, and upregulated the expression of spinal TNFα in the mRNA and the protein levels at 2 weeks after gp120 application. Spinal TNFα was colocalized with GFAP (a marker of astrocytes) and Iba1 (a marker of microglia) in immunostaining, suggesting that glia produce TNFα in the spinal cord in this model. Peripheral gp120 application also increased TNFα in the L4/5 DRG. Furthermore, intrathecal administration of TNFα siRNA or soluble TNF receptor reduced gp120 application-induced mechanical allodynia.Our results indicate that TNFα in the spinal cord and the DRG are involved in neuropathic pain, following the peripheral HIV gp120 application, and that blockade of the glial product TNFα reverses neuropathic pain induced by HIV gp120 application.Infection of the central nervous system with the human immunodeficiency virus type 1 (HIV-1) can lead to cognitive, motor and sensory disorders. HIV-associated sensory neuropathy (HIV-SN) is one of the most common forms of peripheral neuropathy, affecting about 30% of people with acquired immune deficiency syndrome (AIDS) [1,2]. The symptoms of HIV-SN are dominated by neuropathic pain [3,4]. The mechanisms underlying HIV-SN remain unclear. Astrocytosis and subsequent neuron death are two hallmarks of HIV infection in the central nervous system[5]. Direct infection of neurons by HIV is thought to be unlikely [6,7]; HIV-1 binds via the external envelope proteins (e.g., gp120) to the chemokine receptors CXCR4 and/or CCR5 (co-receptors of gp120) on the cells. Previous reports have suggested that gp120 application contributes to neurotoxicity in in vitro and nociceptive behaviour in rodents [8-11]. Indeed, it has been demonstrated that gp120 application is capable of producing pain when administered peripherally [12] or centrally [13]. Proposed mechanisms underlying gp120 application induced a chronic nociceptive effect included spin
The 2nd Step by Step International Spinal Cord Repair—Combining research Step by Step into multi-pronged approaches for spinal cord repair  [PDF]
Maria Teresa Moreno-Flores, Francois Ferón, Victor Arvanian, Armin Blesch, Armin Curt, David J. Fink, Marina Mata, Kinichi Nakashima, Xavier Navarro, Francisco Javier Rodríguez, Michal Schwartz, Mikael Svensson, Erik Sundstrom, Joan Romero, Filip Lim
Journal of Biomedical Science and Engineering (JBiSE) , 2013, DOI: 10.4236/jbise.2013.67A2003
Abstract: On April 26-27, 2013, the Step by Step Foundation hosted the Second International Spinal Cord Repair Meeting at the Fira Barcelona Convention Center in Hospitalet de Llobregat, Spain, highlighting some of the exciting research including clinical trials which show promise for treatments for this devastating disorder. This meeting brought together clinicians, clinical scientists and molecular biologists from more than 10 countries to evaluate current knowledge on clinical, cellular, and biomolecular aspects of spinal cord injury. A major goal of the conference in advancing the translation of research data to the clinic was to promote multi-pronged approaches for therapy of this complex problem.
Parkinson Subtypes Progress Differently in Clinical Course and Imaging Pattern
Carsten Eggers, David J. Pedrosa, Deniz Kahraman, Franziska Maier, Catharine J. Lewis, Gereon R. Fink, Matthias Schmidt, Lars Timmermann
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046813
Abstract: Objective To elucidate whether Parkinson’s disease (PD) subtypes show a differential pattern of FP-CIT-SPECT binding during the disease course. Methods We examined 27 patients (10 female, 17 male, mean age 61.68±11.24 years, 14 tremordominant, 13 akinetic-rigid) with [123I]FP-CIT-SPECT and clinical ratings including UPDRS III after at baseline and after a mean period of 2.47 years. Patients had been classified at baseline as tremordominant or akinetic-rigid according to a “tremor score” and “non-tremor score”. These subgroups were compared for differences in disease progression. Means of clinical ratings and the quantitative analyses of FP-CIT-SPECT for ipsi- and contralateral putamen and caudate nucleus were calculated and compared between baseline and follow-up. Results There were no statistical differences concerning age, disease duration, L-Dopa equivalent dose, disease severity (UPDRS III) or dopaminergic uptake in FP-CIT-SPECT at baseline between both subgroups. At follow-up, akinetic-rigid patients showed a distinct and statistically significant reduction of the dopaminergic uptake associated with significant progression of the clinical symptoms (UPDRS III). In contrast, in tremor patients the aggravation of clinical symptoms and dopaminergic deficit was less pronounced without statistical significance among assessments. Conclusions This study shows for the first time a considerable progression of clinical symptoms and in-vivo dopaminergic deficit of akinetic-rigid compared to tremordominant PD patients over time. Our data may help to improve strategic planning of further therapeutic trials and to provide a clearer prognosis for patients regarding the perspective of their disease.
Frenkel and charge transfer excitons in C60
M. Knupfer,J. Fink
Physics , 1999, DOI: 10.1103/PhysRevB.60.10731
Abstract: We have studied the low energy electronic excitations of C60 using momentum dependent electron energy-loss spectroscopy in transmission. The momentum dependent intensity of the gap excitation allows the first direct experimental determination of the energy of the 1Hg excitation and thus also of the total width of the multiplet resulting from the gap transition. In addition, we could elucidate the nature of the following excitations - as either Frenkel or charge transfer excitons.
K-classes of matroids and equivariant localization
Alex Fink,David E Speyer
Mathematics , 2010,
Abstract: To every matroid, we associate a class in the K-theory of the Grassmannian. We study this class using the method of equivariant localization. In particular, we provide a geometric interpretation of the Tutte polynomial. We also extend results of the second author concerning the behavior of such classes under direct sum, series and parallel connection and two-sum; these results were previously only established for realizable matroids, and their earlier proofs were more difficult.
Towards SiPM camera for current and future generations of Cherenkov telescopes
Daniel Mazin,Priyadarshini Bangale,Julian Sitarek,Juan Cortina,David Fink,Jürgen Hose,Jose Maria Illa,Eckart Lorenz,Manel Martínez,Uta Menzel,Razmik Mirzoyan,Masahiro Teshima
Physics , 2014,
Abstract: So far the current ground-based Imaging Atmospheric Cherenkov Telescopes (IACTs) have energy thresholds in the best case in the range of ~30 to 50 GeV (H.E.S.S. II and MAGIC telescopes). Lowest energy gamma-ray showers produce low light intensity images and cannot be efficiently separated from dominating images from hadronic background. A cost effective way of improving the telescope performance at lower energies is to use novel photosensors with superior photon detection efficiency (PDE). Currently the best commercially available superbialkali photomultipliers (PMTs) have a PDE of about 30-33%, whereas the silicon photomultipliers (SiPMs, also known as MPPC, GAPD) from some manufacturers show a photon detection efficiency of about 40-45%. Using these devices can lower the energy threshold of the instrument and may improve the background rejection due to intrinsic properties of SiPMs such as a superb single photoelectron resolution. Compared to PMTs, SiPMs are more compact, fast in response, operate at low voltage, and are insensitive to magnetic fields. SiPMs can be operated at high background illumination, which would allow to operate the IACT also during partial moonlight, dusk and dawn, hence increasing the instrument duty cycle. We are testing the SiPMs for Cherenkov telescopes such as MAGIC and CTA. Here we present an overview of our setup and first measurements, which we perform in two independent laboratories, in Munich, Germany and in Barcelona, Spain.
I Am Not a Scientist, I Am a Number
Philip E. Bourne ,J. Lynn Fink
PLOS Computational Biology , 2008, DOI: 10.1371/journal.pcbi.1000247
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