botulinum toxins

Summary

Summary: Proteins synthesized as a single chain of ~150 kDa with 35% sequence identity to TETANUS TOXIN that is cleaved to a light and a heavy chain that are linked by a single disulfide bond. They have neuro-, entero-, and hemotoxic properties, are immunogenic, and include the most potent poisons known. The most commonly used apparently blocks release of ACETYLCHOLINE at cholinergic SYNAPSES.

Top Publications

  1. pmc Genetic diversity among Botulinum Neurotoxin-producing clostridial strains
    K K Hill
    Bioscience, Theoretical Divisions, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
    J Bacteriol 189:818-32. 2007
  2. pmc Analysis of Clostridium botulinum serotype E strains by using multilocus sequence typing, amplified fragment length polymorphism, variable-number tandem-repeat analysis, and botulinum neurotoxin gene sequencing
    Thomas E Macdonald
    Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
    Appl Environ Microbiol 77:8625-34. 2011
  3. ncbi A novel strain of Clostridium botulinum that produces type B and type H botulinum toxins
    Jason R Barash
    Infant Botulism Treatment and Prevention Program, California Department of Public Health, Richmond, California
    J Infect Dis 209:183-91. 2014
  4. pmc Glycosylated SV2 and gangliosides as dual receptors for botulinum neurotoxin serotype F
    Zhuji Fu
    Department of Biochemistry, Medical Collegeof Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA
    Biochemistry 48:5631-41. 2009
  5. ncbi Assessment: Botulinum neurotoxin for the treatment of spasticity (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology
    D M Simpson
    Department of Neurology, Mount Sinai Medical Center, New York, NY, USA
    Neurology 70:1691-8. 2008
  6. ncbi The structure and mode of action of different botulinum toxins
    J O Dolly
    International Centre for Neurotherapeutics, Dublin City University, Glasnevin, Dublin, Ireland
    Eur J Neurol 13:1-9. 2006
  7. pmc Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin
    Yo Sugawara
    Laboratory for Infection Cell Biology, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565 0871, Japan
    J Cell Biol 189:691-700. 2010
  8. ncbi Immunological aspects of Botox, Dysport and Myobloc/NeuroBloc
    D Dressler
    Department of Neurology, Rostock University, Rostock, Germany
    Eur J Neurol 13:11-5. 2006
  9. ncbi Cross reaction of tetanus and botulinum neurotoxins A and B and the boosting effect of botulinum neurotoxins A and B on a primary anti-tetanus antibody response
    Behzod Z Dolimbek
    Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA
    Immunol Invest 31:247-62. 2002
  10. ncbi Clostridium botulinum and its neurotoxins: a metabolic and cellular perspective
    E A Johnson
    Department of Food Microbiology and Toxicology, and Bacteriology, Food Research Institute, University of Wisconsin, Madison, 53706, USA
    Toxicon 39:1703-22. 2001

Detail Information

Publications327 found, 100 shown here

  1. pmc Genetic diversity among Botulinum Neurotoxin-producing clostridial strains
    K K Hill
    Bioscience, Theoretical Divisions, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
    J Bacteriol 189:818-32. 2007
    ..These analyses contribute to the understanding of the evolution and phylogeny within this species and assist in the development of improved diagnostics and therapeutics for the treatment of botulism...
  2. pmc Analysis of Clostridium botulinum serotype E strains by using multilocus sequence typing, amplified fragment length polymorphism, variable-number tandem-repeat analysis, and botulinum neurotoxin gene sequencing
    Thomas E Macdonald
    Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
    Appl Environ Microbiol 77:8625-34. 2011
    ....
  3. ncbi A novel strain of Clostridium botulinum that produces type B and type H botulinum toxins
    Jason R Barash
    Infant Botulism Treatment and Prevention Program, California Department of Public Health, Richmond, California
    J Infect Dis 209:183-91. 2014
    ....
  4. pmc Glycosylated SV2 and gangliosides as dual receptors for botulinum neurotoxin serotype F
    Zhuji Fu
    Department of Biochemistry, Medical Collegeof Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA
    Biochemistry 48:5631-41. 2009
    ..Thus, BoNT/F neuronal discrimination involves the recognition of ganglioside and protein (glycosylated SV2) carbohydrate moieties, providing a structural basis for the high affinity and specificity of BoNT/F for neurons...
  5. ncbi Assessment: Botulinum neurotoxin for the treatment of spasticity (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology
    D M Simpson
    Department of Neurology, Mount Sinai Medical Center, New York, NY, USA
    Neurology 70:1691-8. 2008
    ..To perform an evidence-based review of the safety and efficacy of botulinum neurotoxin (BoNT) in the treatment of adult and childhood spasticity...
  6. ncbi The structure and mode of action of different botulinum toxins
    J O Dolly
    International Centre for Neurotherapeutics, Dublin City University, Glasnevin, Dublin, Ireland
    Eur J Neurol 13:1-9. 2006
    ..The widespread cellular distribution of SNAP-25 and the diversity of the toxin's neuronal acceptors are being exploited for other therapeutic applications...
  7. pmc Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin
    Yo Sugawara
    Laboratory for Infection Cell Biology, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565 0871, Japan
    J Cell Biol 189:691-700. 2010
    ..These data demonstrate that botulinum HA directly binds E-cadherin and disrupts E-cadherin-mediated cell to cell adhesion in a species-specific manner and that the HA-E-cadherin interaction is essential for the disruption of TJ function...
  8. ncbi Immunological aspects of Botox, Dysport and Myobloc/NeuroBloc
    D Dressler
    Department of Neurology, Rostock University, Rostock, Germany
    Eur J Neurol 13:11-5. 2006
    ..To determine the antigenicity of different BT preparations in more detail, prospective studies on large series of unbiased patients with sensitive and specific BT antibody tests are necessary...
  9. ncbi Cross reaction of tetanus and botulinum neurotoxins A and B and the boosting effect of botulinum neurotoxins A and B on a primary anti-tetanus antibody response
    Behzod Z Dolimbek
    Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA
    Immunol Invest 31:247-62. 2002
    ....
  10. ncbi Clostridium botulinum and its neurotoxins: a metabolic and cellular perspective
    E A Johnson
    Department of Food Microbiology and Toxicology, and Bacteriology, Food Research Institute, University of Wisconsin, Madison, 53706, USA
    Toxicon 39:1703-22. 2001
    ..However, certain areas have not been well-studied, including metabolic regulation of toxin formation and genetic tools to study neurotoxigenic clostridia. These topics are the focus of this review...
  11. ncbi Synaptobrevin I mediates exocytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential
    Jianghui Meng
    International Centre for Neurotherapeutics, Dublin City University, Glasnevin, Dublin 9, Ireland
    J Cell Sci 120:2864-74. 2007
    ..Such use of particular Sbr isoform(s) by different neurons raises the functional implications for other cells previously unrecognised...
  12. ncbi SNAP-25 modulation of calcium dynamics underlies differences in GABAergic and glutamatergic responsiveness to depolarization
    Claudia Verderio
    Department of Medical Pharmacology, CNR Institute of Neuroscience, Center of Excellence for Neurodegenerative Diseases, University of Milano, Via Vanvitelli 32, Milano 20129, Italy
    Neuron 41:599-610. 2004
    ..hippocampal GABAergic synapses, both in culture and in brain, lack SNAP-25 and are resistant to the action of botulinum toxins type A and E, which cleave this SNARE protein...
  13. ncbi Proteolysis of SNAP-25 by types E and A botulinal neurotoxins
    T Binz
    Department of Microbiology, Federal Research Center of Virus Diseases of Animals, Tubingen, Germany
    J Biol Chem 269:1617-20. 1994
    ....
  14. pmc Recombination and insertion events involving the botulinum neurotoxin complex genes in Clostridium botulinum types A, B, E and F and Clostridium butyricum type E strains
    Karen K Hill
    Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    BMC Biol 7:66. 2009
    ..The four species have been classified as C. botulinum Groups I-IV. The presence of bont genes in strains representing the different Groups is probably the result of horizontal transfer of the toxin operons between the species...
  15. ncbi Detection of antibodies against botulinum toxins
    Dorothea Sesardic
    Division of Bacteriology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, United Kingdom
    Mov Disord 19:S85-91. 2004
    ..Most recent promising developments are focused on cellular assays utilising primary rat embryonic cord cells or more conveniently in vitro differentiated established cell lines such as human neuroblastoma cells...
  16. ncbi Treatment options for hyperhidrosis
    Hobart W Walling
    Am J Clin Dermatol 12:285-95. 2011
    ..Topical medications or botulinum toxin injections may be useful in some cases and ETS is an option for severe craniofacial hyperhidrosis...
  17. ncbi Use of botulinum toxin in the neurology clinic
    Erle C H Lim
    Division of Neurology, National University Health System, National University of Singapore, 1E, NUHS Tower Block, Kent Ridge Road, Singapore 119228
    Nat Rev Neurol 6:624-36. 2010
    ..Important practical aspects, such as the reconstitution of BoNT, dosing, and methods of administration, are also addressed...
  18. ncbi Neurotoxin gene clusters in Clostridium botulinum type A strains: sequence comparison and evolutionary implications
    Sean S Dineen
    Department of Food Microbiology and Toxicology, Food Research Institute, University of Wisconsin, 1925 Willow Drive, Madison, WI 53706, USA
    Curr Microbiol 46:345-52. 2003
    ..These IS elements may have played a role in neurotoxin gene transfer within the host genome and to other Clostridium species...
  19. pmc Evidence that plasmid-borne botulinum neurotoxin type B genes are widespread among Clostridium botulinum serotype B strains
    Giovanna Franciosa
    Department of Food Safety and Veterinary Public Health, Unit of Microorganisms and Food Technologies, Istituto Superiore di Sanita, Rome, Italy
    PLoS ONE 4:e4829. 2009
    ..botulinum type B, Ab, and A(B), and whether plasmid carriage is bont/B subtype-related...
  20. pmc Molecular assembly of botulinum neurotoxin progenitor complexes
    Desirée A Benefield
    Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville TN 37232, USA
    Proc Natl Acad Sci U S A 110:5630-5. 2013
    ..The structures highlight an effective platform that can be engineered for the development of mucosal vaccines and the intestinal absorption of oral biologics...
  21. pmc De novo subtype and strain identification of botulinum neurotoxin type B through toxin proteomics
    Suzanne R Kalb
    Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, Atlanta, GA 30341, USA
    Anal Bioanal Chem 403:215-26. 2012
    ..These techniques allow for subtype and strain level identification of both known and unknown BoNT/B rapidly with no DNA required...
  22. ncbi FK506-binding protein 51 interacts with Clostridium botulinum C2 toxin and FK506 inhibits membrane translocation of the toxin in mammalian cells
    Eva Kaiser
    Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Albert Einstein Allee 11, Ulm, Germany
    Cell Microbiol 14:1193-205. 2012
    ..In conclusion, our results support the hypothesis that clostridial binary actin-ADP-ribosylating toxins share a specific FKBP-dependent translocation mechanism during their uptake into mammalian cells...
  23. ncbi Cyclophilin A facilitates translocation of the Clostridium botulinum C2 toxin across membranes of acidified endosomes into the cytosol of mammalian cells
    Eva Kaiser
    Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Albert Einstein Allee 11, Ulm, Germany
    Cell Microbiol 11:780-95. 2009
    ..In conclusion, our results suggest an essential role of cyclophilin A for translocation of C2I across endosomal membranes during the uptake of C2 toxin into mammalian cells...
  24. ncbi Binary actin-ADP-ribosylating toxins and their use as molecular Trojan horses for drug delivery into eukaryotic cells
    Holger Barth
    Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Albert Einstein Allee 11, D 89081 Ulm, Germany
    Curr Med Chem 15:459-69. 2008
    ..This review will focus on the recent progress in studying binary actin ADP-ribosylating toxins as highly effective virulence factors and innovative tools for cell physiology as well as pharmacology...
  25. ncbi BotR/A and TetR are alternative RNA polymerase sigma factors controlling the expression of the neurotoxin and associated protein genes in Clostridium botulinum type A and Clostridium tetani
    Stephanie Raffestin
    Institut Pasteur, Unité des Bactéries anaérobies et Toxines, 25 28 rue du Dr Roux 75724, Paris Cedex 15, France
    Mol Microbiol 55:235-49. 2005
    ..botulinum, C. tetani, C. difficile and C. perfringens. Overall, a common regulation mechanism probably controls toxin gene expression in these four toxigenic clostridial species...
  26. ncbi Presynaptic receptor arrays for clostridial neurotoxins
    Cesare Montecucco
    Dipartimento di Scienze Biomediche and Istituto CNR di Neuroscienze, Università de Padova, Via G Colombo 3, 35121 Padua, Italy
    Trends Microbiol 12:442-6. 2004
  27. ncbi Beyond BOTOX: advantages and limitations of individual botulinum neurotoxins
    Bazbek Davletov
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Trends Neurosci 28:446-52. 2005
    ..The distinct behaviors of botulinum neurotoxins will be discussed, with the aim of highlighting advantages and limitations for their future exploitation...
  28. ncbi Long-lasting benefits of botulinum toxin type B in Parkinson's disease-related drooling
    Giovanni Lagalla
    Clinica Neurologica, Dipartimento di Neuroscienze, Universita Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy
    J Neurol 256:563-7. 2009
    ..To investigate the safety, efficacy and effectiveness of botulinum toxin type-B (BTX-B) injections into the parotid glands to reduce drooling in Parkinson's disease (PD) subjects...
  29. ncbi Basic immunological aspects of botulinum toxin therapy
    M Zouhair Atassi
    Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mov Disord 19:S68-84. 2004
    ....
  30. ncbi Botulinum toxin A versus B in sialorrhea: a prospective, randomized, double-blind, crossover pilot study in patients with amyotrophic lateral sclerosis or Parkinson's disease
    Arianna Guidubaldi
    Istituto di Neurologia, Universita Cattolica del Sacro Cuore, Roma, Italia
    Mov Disord 26:313-9. 2011
    Either botulinum toxins (BoNTs) A and B have been used for improving drooling in different neurological conditions.
  31. ncbi Botulinum toxin changes intrafusal feedback in dystonia: a study with the tonic vibration reflex
    Carlo Trompetto
    Dipartimento di Neuroscienze, Oftalmologia e Genetica, Universita di Genova, Italia
    Mov Disord 21:777-82. 2006
    ..The action on intrafusal fibers could alter sensorimotor integration, thus contributing to the clinical benefits of BT-A injection...
  32. pmc Long-term follow-up of botulinum toxin therapy for focal hand dystonia: outcome at 10 years or more
    Codrin Lungu
    Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
    Mov Disord 26:750-3. 2011
    ..Previous studies have explored the efficacy and safety of botulinum neurotoxin (BoNT) treatment for Focal hand dystonia (FHD), but none have followed a large number of patients for 10 years or more...
  33. ncbi Clinical use of non-A botulinum toxins: botulinum toxin type B
    D Dressler
    Department of Neurology, Rostock University, Germany
    Neurotox Res 9:121-5. 2006
    ..Systemic anticholinergic adverse effects and high antigenicity limits the clinical use of NeuroBloc/MyoBloc considerably...
  34. ncbi Uptake of botulinum neurotoxin into cultured neurons
    James E Keller
    Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Biochemistry 43:526-32. 2004
    ..This study demonstrates that uptake of both BoNT-A and -E is enhanced with synaptic activity and that translocation of the toxin catalytic moiety into the cytosol occurs at different rates for these two serotypes...
  35. pmc Insights into the different catalytic activities of Clostridium neurotoxins
    Sheng Chen
    Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR
    Biochemistry 51:3941-7. 2012
    ..most potent protein toxins for humans and are responsible for botulism, a flaccid paralysis elicited by the botulinum toxins (BoNT), and spastic paralysis elicited by tetanus toxin (TeNT)...
  36. ncbi Extravesicular intraneuronal migration of internalized botulinum neurotoxins without detectable inhibition of distal neurotransmission
    Gary W Lawrence
    International Centre for Neurotherapeutics, Dublin City University, Glasnevin, Dublin 9, Ireland
    Biochem J 441:443-52. 2012
    ..Spontaneous or evoked transmission to cell bodies were not inhibited by retrogradely migrated BoNTA except with high doses, concurring with the lack of evidence for a direct central action when used clinically...
  37. pmc Structural analysis of botulinum neurotoxin type G receptor binding
    John Schmitt
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Biochemistry 49:5200-5. 2010
    ..The BoNT/G receptor-binding domain crystal structure provides a context for examining these binding interactions and a platform for understanding the physiological relevance of different Syt receptor isoforms in vivo...
  38. ncbi Neuro-exocytosis: botulinum toxins as inhibitory probes and versatile therapeutics
    J Oliver Dolly
    International Centre for Neurotherapeutics, Dublin City University, Glasnevin, Dublin 9, Ireland
    Curr Opin Pharmacol 9:326-35. 2009
    ....
  39. ncbi Multiplex detection of microbial and plant toxins by immunoaffinity enrichment and matrix-assisted laser desorption/ionization mass spectrometry
    Skadi Kull
    Biomedical Spectroscopy P25, Robert Koch Institut, Nordufer 20, 13353 Berlin, Germany
    Anal Chem 82:2916-24. 2010
    ..Furthermore, the MALDI-based multiplex assay allowed for the discrimination of closely related BoNT sero- and subtypes, including a real case of food-borne botulism in Germany...
  40. ncbi Simultaneous multiplex detection and confirmation of the proteinaceous toxins abrin, ricin, botulinum toxins, and Staphylococcus enterotoxins a, B, and C in food
    Eric A E Garber
    Office of Regulatory Science, Center for Food Safety and Applied Nutrition, Food and Drug Administration, 5100 Paint Branch Parkway, College Park, Maryland 20740, USA
    J Agric Food Chem 58:6600-7. 2010
    ..Polyclonal and monoclonal antibodies were obtained for abrin, botulinum toxins, ricin, and Staphylococcus enterotoxins A, B, and C (SEA, SEB, and SEC)...
  41. ncbi Human botulism immune globulin for the treatment of infant botulism
    Stephen S Arnon
    Infant Botulism Treatment and Prevention Program, California Department of Health Services, Richmond, CA 94804, USA
    N Engl J Med 354:462-71. 2006
    ..We created the orphan drug Human Botulism Immune Globulin Intravenous (Human) (BIG-IV), which neutralizes botulinum toxin, and evaluated its safety and efficacy in treating infant botulism, the intestinal-toxemia form of human botulism...
  42. pmc Conjugative botulinum neurotoxin-encoding plasmids in Clostridium botulinum
    Kristin M Marshall
    Department of Bacteriology, College of Agriculture and Life Sciences, University of Wisconsin, Madison, Wisconsin, USA
    PLoS ONE 5:e11087. 2010
    ..The objective of the present study was to determine whether these C. botulinum BoNT-encoding plasmids are conjugative...
  43. ncbi The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption
    Takuhiro Matsumura
    Laboratory for Infection Cell Biology, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Cell Microbiol 10:355-64. 2008
    ..These studies show that the 16S BoNT complex is a multifunctional protein assembly equipped with the machinery to efficiently breach the intestinal barrier and act systemically on peripheral nerves...
  44. ncbi Botulinum neurotoxin: a marvel of protein design
    Mauricio Montal
    Section of Neurobiology, Division of Biological Sciences, University of California San Diego, La Jolla, California 92093 0366, USA
    Annu Rev Biochem 79:591-617. 2010
    ..Understanding the design principles underpinning the function of such a dynamic modular protein remains a challenging task...
  45. ncbi Assessment: Botulinum neurotoxin for the treatment of movement disorders (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology
    D M Simpson
    Department of Neurology, Mount Sinai Medical Center, New York, NY, USA
    Neurology 70:1699-706. 2008
    ..To perform an evidence-based review of the safety and efficacy of botulinum neurotoxin (BoNT) in the treatment of movement disorders...
  46. ncbi Channel formation by the binding component of Clostridium botulinum C2 toxin: glutamate 307 of C2II affects channel properties in vitro and pH-dependent C2I translocation in vivo
    Dagmar Blöcker
    Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert Ludwigs Universitat Freiburg, Otto Krayer Haus, Albertstrasse 25, D 79104 Freiburg, Germany
    Biochemistry 42:5368-77. 2003
    ..Overall, the voltage gating and cation selectivity of the C2II channel do not play an important role in translocation of C2I into the cytosol...
  47. pmc Botulinum neurotoxin D uses synaptic vesicle protein SV2 and gangliosides as receptors
    Lisheng Peng
    Department of Microbiology and Molecular Genetics, Harvard Medical School and Division of Neuroscience, New England Primate Research Center, Southborough, Massachusetts, United States of America
    PLoS Pathog 7:e1002008. 2011
    ..Finally, we demonstrated that gangliosides are essential for the binding and entry of BoNT/D into neurons and for its toxicity in vivo, supporting a double-receptor model for this toxin...
  48. ncbi rac, a novel ras-related family of proteins that are botulinum toxin substrates
    J Didsbury
    Department of Pharmacological Sciences, Genentech, Incorporated, South San Francisco, California 94080
    J Biol Chem 264:16378-82. 1989
    ..The data suggest that racs are plasma membrane-associated GTP-binding proteins which could regulate secretory processes, particularly in myeloid cells...
  49. ncbi Botulinum neurotoxin E (BoNT/E) reduces CA1 neuron loss and granule cell dispersion, with no effects on chronic seizures, in a mouse model of temporal lobe epilepsy
    Flavia Antonucci
    Istituto di Neuroscienze C N R, Pisa, Italy
    Exp Neurol 210:388-401. 2008
    ..This indicates a dissociation between certain anatomical modifications and establishment of chronic epilepsy in MTLE...
  50. ncbi Is the light chain subcellular localization an important factor in botulinum toxin duration of action?
    Ester Fernandez-Salas
    Neurotoxin Research Program, Department of Biological Sciences, Allergan Inc, Irvine, California 92612, USA
    Mov Disord 19:S23-34. 2004
    ....
  51. ncbi Clostridial toxins as therapeutic agents: benefits of nature's most toxic proteins
    E A Johnson
    Department of Food Microbiology and Toxicology, University of Wisconsin, Madison 53706, USA
    Annu Rev Microbiol 53:551-75. 1999
    ..The remarkable success of botulinum toxin as a therapeutic agent has created a new field of investigation in microbiology...
  52. ncbi Botulinum toxin: mechanisms of action
    Dirk Dressler
    Department of Neurology, Rostock University, Rostock, Germany
    Eur Neurol 53:3-9. 2005
    ..Reduction of formalin-induced pain suggests direct analgesic BT effects possibly mediated by blockade of substance P, glutamate and calcitonin gene-related peptide...
  53. pmc Llama single domain antibodies specific for the 7 botulinum neurotoxin serotypes as heptaplex immunoreagents
    Jerry O Conway
    Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas, United States of America
    PLoS ONE 5:e8818. 2010
    ..Here we employ facile recombinant antibody technology to subtractively select ligands to each of the 7 BoNT serotypes, resulting in populations with very high specificity for their intended serotype...
  54. ncbi Clostridium botulinum C2 toxin: low pH-induced pore formation is required for translocation of the enzyme component C2I into the cytosol of host cells
    Dagmar Blöcker
    Institut fur Experimentelle und Klinische Pharmakologie, Albertstrasse 25, Otto Krayer Haus, D 79104 Freiburg, Germany
    J Biol Chem 278:37360-7. 2003
    ..Intoxication of target cells with C2 toxin requires a strictly coordinated pH-dependent sequence of binding, pore formation by C2IIa, and translocation of C2I...
  55. ncbi Botulinum toxin therapy for cervical dystonia
    J Jankovic
    Parkinson s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
    Neurotox Res 9:145-8. 2006
    ..This review provides and update on the treatment of CD with BoNT type A (BOTOX, Dysport, Xeomin and BoNT type B (Myobloc, NeuroBloc...
  56. ncbi Traffic of botulinum toxins A and E in excitatory and inhibitory neurons
    Claudia Verderio
    Department of Medical Pharmacology, University of Milano, Via Vanvitelli 32, 20129 Milano, Italy
    Traffic 8:142-53. 2007
    ....
  57. pmc Plasma membrane localization signals in the light chain of botulinum neurotoxin
    Ester Fernandez-Salas
    Neurotoxin Research Program, Department of Biological Sciences, Allergan Inc, 2525 Dupont Drive, Irvine, CA 92612 1599, USA
    Proc Natl Acad Sci U S A 101:3208-13. 2004
    ..These data support sequence-specific signals as determinants of intracellular localization and as a basis for the different durations of action in these two BoNT serotypes...
  58. ncbi Transient synaptic silencing of developing striate cortex has persistent effects on visual function and plasticity
    Matteo Caleo
    Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche, 56100 Pisa, Italy
    J Neurosci 27:4530-40. 2007
    ..Unexpectedly, these effects extended equally to the contralateral, uninjected side, demonstrating a fundamental role for interhemispheric connections in cortical maturation...
  59. ncbi Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology
    M Naumann
    Department of Neurology, Klinikum Augsburg, Germany
    Neurology 70:1707-14. 2008
    ..To perform an evidence-based review of the safety and efficacy of botulinum neurotoxin (BoNT) in the treatment of autonomic and urologic disorders and low back and head pain...
  60. ncbi High-throughput fluorogenic assay for determination of botulinum type B neurotoxin protease activity
    C Anne
    , U266 INSERM, UMR 8600 CNRS, avenue de l'Observatoire, , France
    Anal Biochem 291:253-61. 2001
    ..It can be easily automated for high-throughput screening. Moreover, amounts of about 3.5 pg/ml of botulinum type B neurotoxin could be detected by this method...
  61. ncbi Mosaic structures of neurotoxins produced from Clostridium botulinum types C and D organisms
    K Moriishi
    Department of Veterinary Science, National Institute of Health, Tokyo, Japan
    Biochim Biophys Acta 1307:123-6. 1996
    ..The core region (Pro-523 to Lys-944) is common to three toxins (83% to 92% identity). These results suggest that neurotoxins produced from Clostridium botulinum types C and D are composed in a mosaic-like fashion...
  62. pmc Analysis of a unique Clostridium botulinum strain from the Southern hemisphere producing a novel type E botulinum neurotoxin subtype
    Brian H Raphael
    Centers for Disease Control and Prevention, Atlanta, GA 30329, USA
    BMC Microbiol 12:245. 2012
    ..Previous studies showed that the amino acid sequences of BoNT/E produced by various strains differ by < 6% and that the type E neurotoxin gene cluster inserts into the rarA operon...
  63. pmc TetR is a positive regulator of the tetanus toxin gene in Clostridium tetani and is homologous to botR
    J C Marvaud
    Unité des Toxines Microbiennes, Institut Pasteur, 75724 Paris Cedex 15, France
    Infect Immun 66:5698-702. 1998
    ..This supports that TetR positively regulates the TeTx gene in C. tetani and that a conserved mechanism of regulation of the neurotoxin genes is involved in C. tetani and C. botulinum...
  64. ncbi In vitro reconstitution of the Clostridium botulinum type D progenitor toxin
    Hirokazu Kouguchi
    Department of Food Science and Technology, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099 2493, Japan
    J Biol Chem 277:2650-6. 2002
    ..We conclude that the M toxin forms first by assembly of NT with NTNHA and is subsequently converted to the L toxin by assembly with HA-70 and HA-33/17...
  65. ncbi Cellular uptake of Clostridium botulinum C2 toxin: membrane translocation of a fusion toxin requires unfolding of its dihydrofolate reductase domain
    Gerd Haug
    Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert Ludwigs Universitat Freiburg, Germany
    Biochemistry 42:15284-91. 2003
    ..The data indicate that methotrexate prevented unfolding of the C2I-DHFR fusion toxin, and thereby the translocation of methotrexate-bound C2I-DHFR from endosomes into the cytosol of target cells is inhibited...
  66. ncbi The complete genome sequence of Clostridium botulinum F str. 230613, insertion sites, and recombination of BoNT gene clusters
    Ren Mao Tian
    State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Fengtai District, P R China
    Genome 54:546-54. 2011
    ..Additionally, we found the recombination event between the BoNT gene clusters of sites 2 and 3, a mechanism that contributed to the diversity of the BoNT gene cluster arrangement...
  67. ncbi Carbohydrate recognition mechanism of HA70 from Clostridium botulinum deduced from X-ray structures in complexes with sialylated oligosaccharides
    Satoshi Yamashita
    Life Science Research Center and Faculty of Medicine, Kagawa University, 1750 1 Ikenobe, Kita gun, Kagawa 761 0793, Japan
    FEBS Lett 586:2404-10. 2012
    ..These results suggested that HA70/C can recognize both α2-3- and α2-6-sialylated oligosaccharides, and that it has a higher affinity for α2-3-sialylated oligosaccharides...
  68. pmc Bivalent recombinant vaccine for botulinum neurotoxin types A and B based on a polypeptide comprising their effector and translocation domains that is protective against the predominant A and B subtypes
    Clifford Shone
    Health Protection Agency, Porton Down, Salisbury, Wilts, United Kingdom
    Infect Immun 77:2795-801. 2009
    ..In addition, LH(N)/B provided single-dose protection in mice against BoNT/B(4) (nonproteolytic toxin subtype)...
  69. pmc Neurotoxin gene profiling of clostridium botulinum types C and D native to different countries within Europe
    Cedric Woudstra
    ANSES French Agency for Food, Environmental and Occupational Health Safety, Food Safety Laboratory, Maisons Alfort, France
    Appl Environ Microbiol 78:3120-7. 2012
    ..Further investigations should now be performed in order to check that mosaic types dominate in Europe and that acquisition of mosaic types helps in survival or adaptation to particular niche...
  70. ncbi Rapid and selective detection of botulinum neurotoxin serotype-A and -B with a single immunochromatographic test strip
    Kathryn H Ching
    United States Department of Agriculture, Agricultural Research Service, Western Regional Research Center, 800 Buchanan St, RM 2124, Albany, CA 94710, USA
    J Immunol Methods 380:23-9. 2012
    ..These attributes make this rapid diagnostic device a potentially valuable tool in the fields of food safety and homeland security...
  71. ncbi Development of real-time PCR tests for detecting botulinum neurotoxins A, B, E, F producing Clostridium botulinum, Clostridium baratii and Clostridium butyricum
    P Fach
    Agence Francaise de Securite Sanitaire des Aliments, Laboratoire d Etudes et de Recherches sur la Qualité des Aliments et les Procédés Agro alimentaires, Maisons Alfort, France
    J Appl Microbiol 107:465-73. 2009
    ..To develop real-time PCR assays for tracking and tracing clostridia responsible for human botulism...
  72. ncbi Type C botulinum toxin causes degeneration of motoneurons in vivo
    Li Chun Zhao
    Center for Neuroscience, Aging and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Neuroreport 21:14-8. 2010
    All botulinum toxins (BoNTs, types A-G) inhibit synaptic transmitter release from motoneurons, and thus result in respiratory arrest and death...
  73. pmc Botulinum toxin injections reduce associative plasticity in patients with primary dystonia
    Maja Kojovic
    Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom
    Mov Disord 26:1282-9. 2011
    ..We propose that subsequent reorganization of the motor cortex representation of hand muscles may explain the effect of botulinum toxin on motor cortical plasticity. © 2011 Movement Disorder Society...
  74. pmc Assembly and function of the botulinum neurotoxin progenitor complex
    Shenyan Gu
    Center for Neuroscience, Aging and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA
    Curr Top Microbiol Immunol 364:21-44. 2013
    ..In this review, we discuss the structural basis for assembly of NAPs and BoNT into the PTC that protects BoNT and facilitate its delivery into the bloodstream...
  75. pmc Sequence diversity of genes encoding botulinum neurotoxin type F
    Brian H Raphael
    Centers for Disease Control and Prevention, Atlanta, GA 30329, USA
    Appl Environ Microbiol 76:4805-12. 2010
    ..These results demonstrate that extensive nucleotide diversity exists among genes encoding type F neurotoxins from strains with different phylogenetic backgrounds and from various geographical sources...
  76. ncbi Rac1, RhoA, and Cdc42 participate in HeLa cell invasion by group B streptococcus
    Carey Ann D Burnham
    The Department of Laboratory Medicine and Pathology, The University of Alberta, Edmonton, AB, Canada
    FEMS Microbiol Lett 272:8-14. 2007
    ..Results of this study suggest that the Rho-family GTPases are required for efficient invasion of HeLa cells by GBS...
  77. ncbi Autonomic side effects of botulinum toxin type B treatment of cervical dystonia and hyperhidrosis
    Dirk Dressler
    Department of Neurology, Rostock University, Rostock, Germany
    Eur Neurol 49:34-8. 2003
    ..Their localization suggests systemic BT-B spread. BT-B should be applied carefully in patients with pre-existent autonomic dysfunction, additional anticholinergic treatment and in conditions where anticholinergics are contraindicated...
  78. ncbi Botulinal neurotoxins: revival of an old killer
    Cesare Montecucco
    Dipartimento di Scienze Biomediche and Istituto CNR di Neuroscienze, Universita di Padova, Viale G Colombo 3, 35131 Padova, Italy
    Curr Opin Pharmacol 5:274-9. 2005
    ..Their range of clinical applications is continuously growing, and BoNT/A is being used extensively as a pharmaco-cosmetic...
  79. pmc Botulinum toxin for writer's cramp: a randomised, placebo-controlled trial and 1-year follow-up
    J J M Kruisdijk
    Department of Neurology and Clinical Neurophysiology, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
    J Neurol Neurosurg Psychiatry 78:264-70. 2007
    ..Botulinum toxin type A (BoNT-A) has become the treatment of choice for most types of focal dystonia...
  80. ncbi Evidence based medicine in the use of botulinum toxin for back pain
    B Jabbari
    Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA
    J Neural Transm 115:637-40. 2008
    ..The second study also depicted safety with repeated injections over 14 months of follow up. Botulinum toxin-A should be considered for treatment of low back pain when other modes of treatment fail to improve pain...
  81. ncbi Efficacy and safety of long-term botulinum toxin treatment in craniocervical dystonia: a systematic review
    Carlo Colosimo
    Dipartimento di Neurologia e Psichiatria, Sapienza Universita di Roma, Viale dell Universita 30, 00185 Rome, Italy
    Neurotox Res 22:265-73. 2012
    ..Longitudinal studies aimed at defining the risk factors for this abnormal pattern of response to botulinum toxin treatment are currently being conducted...
  82. ncbi Glutamate uptake and release by astrocytes are enhanced by Clostridium botulinum C3 protein
    Markus Höltje
    Centrum für Anatomie, Institut für Integrative Neuroanatomie, Charite Universitatsmedizin Berlin, Philippstrasse 12, 10115 Berlin, Germany
    J Biol Chem 283:9289-99. 2008
    ..In conclusion, inhibition of Rho-dependent pathways shifts astrocytes to a secretory active stage in which they may modulate neuronal excitability...
  83. pmc Systemic weakness after therapeutic injections of botulinum toxin a: a case series and review of the literature
    Beth E Crowner
    Program in Physical Therapy, Washington University School of Medicine, St Louis, MO 63108, USA
    Clin Neuropharmacol 33:243-7. 2010
    ..Reduction in systemic side effects may occur if reinjection frequency occurs in intervals of 4 months or greater in these individuals...
  84. ncbi Clostridium botulinum in the post-genomic era
    Michael W Peck
    Institute of Food Research, Norwich Research Park, Colney, Norwich, NR4 7UA, UK
    Food Microbiol 28:183-91. 2011
    ..To better control the botulinum neurotoxin-forming clostridia, it is important to understand spore resistance mechanisms, and the physiological processes involved in germination and lag phase during recovery from this dormant state...
  85. ncbi Treatment of sialorrhea in children with cerebral palsy: a double-blind placebo controlled trial
    Ali H Alrefai
    Jordan University of Science and Technology, Jordan
    Clin Neurol Neurosurg 111:79-82. 2009
    ..To prospectively study the efficacy and safety of intraparotid gland injection of Botulinum neurotoxin serotype A (Dysport) for the treatment of sialorrhea (drooling) in children with cerebral palsy (CP)...
  86. pmc Purification of fully activated Clostridium botulinum serotype B toxin for treatment of patients with dystonia
    Hideyuki Arimitsu
    Department of Bacteriology, Okayama University Graduate School of Medicine and Dentistry, Okayama 700 8558, Japan
    Infect Immun 71:1599-603. 2003
    ..0; the neurotoxin passed through the column, whereas remaining nontoxic components bound to the column. The toxicity of this purified fully activated neurotoxin was retained for a long period by addition of albumin in the preparation...
  87. pmc Multiplex PCR for detection of botulinum neurotoxin-producing clostridia in clinical, food, and environmental samples
    Dario De Medici
    Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy
    Appl Environ Microbiol 75:6457-61. 2009
    ..2%. The multiplex PCR was also used to investigate 110 freshly collected food and environmental samples, and 4 of the 110 samples (3.6%) were positive for BoNT-encoding genes...
  88. ncbi Xeomin in the treatment of cervical dystonia
    R Benecke
    Department of Neurology, University of Rostock, Rostock, Germany
    Eur J Neurol 16:6-10. 2009
    ..Based on its physiochemical properties and toxicological evidence, Xeomin is expected to have a reduced incidence of non-responders after long-term treatment compared with other marketed BoNT/A products...
  89. ncbi A comparison of the safety margins of botulinum neurotoxin serotypes A, B, and F in mice
    K R Aoki
    Allergan, Inc, 2525 Dupont Drive, Irvine, CA 92715, USA
    Toxicon 39:1815-20. 2001
    ..8+/-1.1, respectively). Thus, the BTX preparations exhibited different safety margins in mice. These results support the hypothesis that the preparations are unique therapeutics and are not interchangeable based on a simple dose ratio...
  90. ncbi Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in Parkinson's disease: a prospective double-blind trial
    Robert Chinnapongse
    US WorldMeds, LLC, Louisville, Kentucky 40207, USA
    Mov Disord 27:219-26. 2012
    ..Additional studies are warranted to further confirm the drug's robust efficacy, as well as evaluate its effect with repeated dosing...
  91. ncbi Long-term safety, efficacy, dosing, and development of resistance with botulinum toxin type B in cervical dystonia
    Brian Berman
    University of Colorado School of Medicine, Denver, Colorado, USA
    Mov Disord 20:233-7. 2005
    ..Patients may continue to respond for up to 64 months. Prior Bot A resistance may be a risk factor for the development of resistance to Bot B; nevertheless, Bot B can be a useful long-term alternative in some Bot A-resistant CD patients...
  92. ncbi The role of botulinum toxin in management of pain: an evidence-based review
    Erisela Qerama
    Department of Neurophysiology, Aarhus University Hospital, Aarhus, Denmark
    Curr Opin Anaesthesiol 23:602-10. 2010
    ..In the present review we discuss the role of botulinum neurotoxins (BoNTs) in the management of different pain conditions, with evidence-based data on the toxins' efficacy on pain and its mechanisms...
  93. ncbi Botulinum toxin type B de novo therapy of cervical dystonia: frequency of antibody induced therapy failure
    Dirk Dressler
    Dept of Neurology, Rostock University, Gehlsheimer Str 20, 18147 Rostock, Germany
    J Neurol 252:904-7. 2005
    ..The high amount of neurotoxin administered when NeuroBloc/MyoBloc is used might be a contributory factor. Further prospective comparative studies are necessary to monitor the frequency and time course of BT-B-AB formation...
  94. ncbi Molecular recognition of botulinum neurotoxin B heavy chain by human antibodies from cervical dystonia patients that develop immunoresistance to toxin treatment
    M Zouhair Atassi
    Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Mol Immunol 45:3878-88. 2008
    ..These regions afford candidates for epitope-specific manipulation of anti-toxin immune responses...
  95. pmc Tetanus toxin: primary structure, expression in E. coli, and homology with botulinum toxins
    U Eisel
    EMBO J 5:2495-502. 1986
    ..acid sequences of the tetanus toxin revealed striking homologies with the partial amino acid sequences of botulinum toxins A, B, and E, indicating that the neurotoxins from C. tetani and C...
  96. ncbi Genetically engineered clostridial C2 toxin as a novel delivery system for living mammalian cells
    Jörg Fahrer
    Institute of Pharmacology and Toxicology, University of Ulm, Albert Einstein Allee 47, D 89081 Ulm, Germany
    Bioconjug Chem 21:130-9. 2010
    ..Furthermore, Vero cells treated with biotin-fluorescein or biocytin-Alexa488 as model cargo displayed a specific C2IN-streptavidin/C2IIa-dependent uptake, providing proof-of-principle for the functionality of this novel delivery system...
  97. ncbi A role for the Rho-p160 Rho coiled-coil kinase axis in the chemokine stromal cell-derived factor-1alpha-induced lymphocyte actomyosin and microtubular organization and chemotaxis
    Miguel Vicente-Manzanares
    Servicio de Inmunologia, Hospital de la Princesa, Universidad Autonoma de Madrid, C Diego de Leon, 62, E 28006 Madrid, Spain
    J Immunol 168:400-10. 2002
    ..Our results indicate that the Rho-p160ROCK axis plays a pivotal role in the control of the cell shape as a step before lymphocyte migration toward a chemotactic gradient...
  98. pmc Molecular analysis of an extrachromosomal element containing the C2 toxin gene discovered in Clostridium botulinum type C
    Yoshihiko Sakaguchi
    Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2 5 1 Shikata cho, Okayama 700 8558, Japan
    J Bacteriol 191:3282-91. 2009
    ..In these regions, there were 9 and 11 genes rarely found in plasmids, indicating that this plasmid plays an important role in purine catabolism, as well as in C2 toxin production...
  99. pmc Lipid and cationic polymer based transduction of botulinum holotoxin, or toxin protease alone, extends the target cell range and improves the efficiency of intoxication
    Chueh Ling Kuo
    Tufts Cummings School of Veterinary Medicine, Department of Biomedical Sciences, 200 Westboro Road, North Grafton, MA 01536, USA
    Toxicon 55:619-29. 2010
    ..These results suggest that lipid and cationic polymer transfection reagents facilitate cytosolic delivery of BoNT holotoxins and isolated Lc proteases by an endosomal uptake pathway...
  100. ncbi Monitoring of laying capacity, immunoglobulin Y concentration, and antibody titer development in chickens immunized with ricin and botulinum toxins over a two-year period
    D Pauly
    Robert Koch Institut, Center for Biological Safety, Microbial Toxins, 13353 Berlin, Germany
    Poult Sci 88:281-90. 2009
    ..In summary, we successfully immunized chickens with ricin and botulinum neurotoxins and monitored laying capacity, IgY concentration, and specific antibody titer over an extended period of 2 yr...
  101. ncbi Clostridium botulinum C2 toxin. Identification of the binding site for chloroquine and related compounds and influence of the binding site on properties of the C2II channel
    Tobias Neumeyer
    Lehrstuhl fur Biotechnologie, Theodor Boveri Institut Biozentrum der Universität Würzburg, Am Hubland, D 97074 Wurzburg, Germany
    J Biol Chem 283:3904-14. 2008
    ..The results suggest that amino acids Glu(399), Asp(426), and Phe(428) have a major impact on the function of C2II as a binding protein for C2I delivery into target cells...

Research Grants64

  1. Agrin/alpha 3 Na,K-ATPase signaling at the neuromuscular junction
    Martin A Smith; Fiscal Year: 2012
    ..This novel signal pathway represents a new therapeutic target for the treatment of neuromuscular disease. ..
  2. Robust Peptide-Based Diagnostics of Botulinum Toxins
    John E Mueller; Fiscal Year: 2012
    ..In addition to toxin monitoring, our proposed multiplexed point-of-care diagnostic platform has valuable ramifications for public health by enabling truly individualized medicine. ..
  3. Fast accurate ultrasensitive in vitro assay to determine BoNT potency &stability
    ARMIN H REITMAIR; Fiscal Year: 2012
    ..Therapeutic applications of botulinum toxins have increased steadily over the years requiring new and reliable assays to assess the potency and stability ..
  4. Rapid point-of-care diagnostic for bioterrorism "A" agents and Pandemic influenza
    Kelly J Henrickson; Fiscal Year: 2010
    ..These goals are responsive to a recent NIAID announcement for High- Priority influenza (NOT-AI-05-013) and bio-threat (RFA AI-05-019) research. ..
  5. High-throughput multiplex microsphere screening for toxin protease inhibitors
    Steven W Graves; Fiscal Year: 2012
    ..Both toxins are of interest as they are components of category A biothreat agents, but the botulinum toxins are particularly significant as they are commonly used pharmaceuticals with the potential for tragic misuse...
  6. Effect of botulinum toxin plus vibration on bone in children with cerebral palsy
    Christopher M Modlesky; Fiscal Year: 2012
    ....
  7. Role of Gprotein and SNAP-25 in NMDA vs mGluR presynaptic long-term plasticity
    KATISHA ROSE GOPAUL; Fiscal Year: 2013
    ....
  8. Neurogenic inflammation and psoriasiform dermatitis
    NICOLE LEANNE WARD; Fiscal Year: 2013
    ....
  9. Effect of Articular Neurotoxin on Joint Pain and Neurochemical Signature
    Maren Lawson Mahowald; Fiscal Year: 2012
    ..By discovering new toxins that reduce pain in different ways, we can help to find new treatments for humans with severe arthritis pain. ..
  10. Dynamic Interactions Between G Proteins and Calcium at SNARE Complexes
    Simon T Alford; Fiscal Year: 2013
    ..We will then modify in situ SNARE complex proteins using intracellularly applied Botulinum toxins to compare similar truncations in vitro...
  11. G Protein Coupled Receptor Modulation of Synaptic Transmission
    EDAENI YISHAK HAMID; Fiscal Year: 2010
    ....
  12. Optogenetic inhibition of motor neuron and muscle activity in vivo
    Scott L Delp; Fiscal Year: 2013
    ....
  13. Botulinum toxin in muscles of mastication
    Susan W Herring; Fiscal Year: 2012
    ..The results will guide clinicians in understanding functional consequences and help to validate clinical rationales for treatment. ..
  14. Structure and function of the fingers tendinous apparatus
    Francisco J Valero-Cuevas; Fiscal Year: 2013
    ..Test the emergence and BTX mitigation of whole-finger spasticity, clonus, abnormal postures, and deficits in whole fingertip force tasks. ..
  15. Kinaesthetic Loss as a Marker for Spasmodic Dysphonia
    Peter J Watson; Fiscal Year: 2012
    ....
  16. Novel Pelvic Floor Pain Measures to Enhance Female Pelvic Pain Evaluation
    FRANK FU SHENG TU; Fiscal Year: 2012
    ....
  17. Rho GTPases and Synaptic Morphology: Visualizing the Proteome with FRET Imaging
    Nima Sharifai; Fiscal Year: 2013
    ..By understanding the molecular basis of these processes, medicine will gain novel therapeutic targets to combat the pathophysiologies that afflict those with debilitating neuropsychological conditions. ..
  18. Cerebellar stimulation for the treatment of dystonia: preclinical studies
    Ellen J Hess; Fiscal Year: 2013
    ..The success of this proposal will provide preclinical evidence to support an exploratory clinical study in humans for the use of cerebellar stimulation as a treatment for dystonia. ..
  19. Multiplex Screening Panel for the Detection of Clostridium botulinum Toxin Genes
    Andrew C Whelen; Fiscal Year: 2013
    ..More importantly, it will benefit food surveillance and outbreak investigations not only in Hawaii but also to provide support for the US Affiliated Pacific Islands. ..
  20. TROPHIC MANIPULATIONS OF THE OCULOMOTOR SYSTEM
    Christopher S von Bartheld; Fiscal Year: 2010
    ....
  21. Microfluidic Platform for Multiplexed Diagnostics
    Anup K Singh; Fiscal Year: 2013
    ....
  22. Nurbits: Playing for Success in Neuroscience
    STEPHEN PAUL BORDEN; Fiscal Year: 2013
    ....
  23. Mechanobiology of Rotator Cuff Development
    Stavros Thomopoulos; Fiscal Year: 2013
    ..We will also study the recovery potential of the developing tendon enthesis subjected to varying durations of paralysis and recovery. ..
  24. Voice tremor in spasmodic dysphonia: central mechanisms and treatment response
    Kristina Simonyan; Fiscal Year: 2013
    ....
  25. Muscle Structure, Toxin Dose, and Exercise Affect Botulinum Toxin Efficiency
    SAMUEL RICHARD WARD; Fiscal Year: 2013
    ..The clinical significance of this work lies in the understanding of the interaction between a pharmacological intervention and muscle function. ..
  26. Randomized controlled clinical trial of botulinum toxin for myofascial TMJD pain
    Karen G Raphael; Fiscal Year: 2012
    ....
  27. Intravesical liposome drug delivery to treat interstitial cystitis
    Michael B Chancellor; Fiscal Year: 2012
    ..The knowledge gained as a result of conducting the experiments under this grant will confirm our hypotheses regarding the potential for liquid instillation of botulinum toxin and move toward bring a new treatment for PBS/IC. ..
  28. Physiologic Effects of High-Dose Gastric Antral Botulinum Toxin Injections
    Mark D Topazian; Fiscal Year: 2010
    ..An effective and safe treatment for obesity, delivered during an outpatient endoscopic procedure, would be an attractive treatment option for many obese persons. ..
  29. Rapid detection of botulinum toxins using a high sensitivity SPR sensor
    PAUL MELMAN; Fiscal Year: 2010
    ..Gold nanoparticles will be attached to the peptide to increase the SPR detection sensitivity. An immuno-affinity based sample protocol will be developed to extract and concentrate the target BoNTs from serum. ..
  30. Human Monoclonal Antibodies that Bind Botulinum Toxins
    SCOTT KENDALL DESSAIN; Fiscal Year: 2013
    ..It will also provide a broad understanding of how similar approaches could be used to treat a variety of infectious diseases and toxin exposures. ..
  31. Neuronal Modulation of Focal Bone Homeostasis
    Ted S Gross; Fiscal Year: 2013
    ..If these data support our hypothesis, we believe that our results hold potential to alter current approaches to intervene or prevent bone loss in a variety of musculoskeletal pathologies. ..
  32. Control of Junctional Conductance at Auditory Afferent
    Alberto Pereda; Fiscal Year: 2009
    ..This property could be widespread and relevant to pathological conditions such as epilepsy and developmental disorders. ..
  33. Multiplex PCR Detection of CDC 'A' Bioterrorism Agents
    Kelly Henrickson; Fiscal Year: 2005
    ..Specific Aim 4: To determine if this multiplex assay is equivalent to these "singleplex" assays in a clinical trial. ..
  34. Sensitive Diagnosis of Biowarfare Agents on a Microchip
    Greg Collins; Fiscal Year: 2006
    ..abstract_text> ..
  35. Lateral Rectus Reanimation following Sixth Nerve Palsy
    Arthur Rosenbaum; Fiscal Year: 2006
    ..The final implanted device will encompass the stimulation control system, which will be optimized in individual tests within our laboratory setting. ..
  36. Multiplexed POC Diagnostic System for Bio-Threat Agents
    GEORGE SIGAL; Fiscal Year: 2005
    ..The system is designed to be used by personnel without specialized training and will require no pre-processing of samples. ..
  37. DOUBLE-BLIND BOTULINUM TOXIN FOR SPASMODIC DYSPHONIA
    Mitchell Brin; Fiscal Year: 1991
    ....
  38. A novel vaccine: botulinum neurotoxin subunit on a viral carrier.
    MATTHIAS JOHANNES SCHNELL; Fiscal Year: 2013
    ..Specific Aim 3: Development of Pilot Production and Purification Processes. The overall goal of this aim is to translate the production process of our vaccine from a research setting to one suitable for pilot scale vaccine manufacture. ..
  39. Diphtheria & Anthrax Toxins: Mechanisms of Cell Entry
    John Murphy; Fiscal Year: 2007
    ..In the case of diphtheria toxin, anthrax toxins, and botulinum toxins a great deal is known of their respective structure function domains and their mode of action; however, a ..
  40. Botulinum Toxin Plantibodies
    KEITH WYCOFF; Fiscal Year: 2002
    ..James D. Marks of the UC San Francisco School of Medicine. Botulinum toxins (BoNT) are extremely potent neurotoxins produced by the anaerobic bacterium Clostridium botulinum...
  41. Nuclease-Resistant Aptamers to Botox and Anthrax Toxins
    John Bruno; Fiscal Year: 2004
    ..Such reagents could also be used in environmental biosensors or diagnostic test kits for detection of BOTOX and anthrax toxins in body fluids or environmental samples. ..
  42. CHEMOMYECTOMY FOR EYELID SPASMS
    Linda McLoon; Fiscal Year: 1999
    ..These studies will allow us to develop the most clinically effective and cost effective treatment for these patients. ..
  43. NEUROMUSCULAR TARGETS OF BOTULINUM TOXIN
    JULIE COFFIELD; Fiscal Year: 2006
    ..Substantial evidence indicates that productive binding of botulinum toxins requires both polysialogangliosides and glycoproteins...
  44. ASPARTATE TRANSMISSION
    J Victor Nadler; Fiscal Year: 2005
    ..This project will eventually shed light on developmental and neurodegenerative processes, including the pathophysiology and pathology associated with epileptic seizures and hypoglycemia. ..
  45. BLOCKAGE OF TOXIN-CELL INTERACTIONS BY OLIGOSACCHARIDES
    Cara Lynne Schengrund; Fiscal Year: 1993
    ..Three botulinum toxins (A,B and E) will be studied to determine whether observations made with one toxin (botulinum toxin A) might ..
  46. The Role of p75 Receptor in Tetanus Toxin Transport
    Rafal Butowt; Fiscal Year: 2005
    ..1992; Schneider et al., 2000; Schiavo et al., 2000; Bordet et al., 2001; Kissa et al., 2002). ..
  47. Planning Grant for SOD III Multicenter Trial
    Peter Cotton; Fiscal Year: 2004
    ..This trial will answer several of the important questions raised by the expert panel at the NIH State of the Science of ERCP Conference, held in January. ..
  48. Interstitial Cystitis Clinical Research Network
    Toby Chai; Fiscal Year: 2007
    ..The goals of the University of Maryland clinical site are to maximize enrollment of IC patients into innovative clinical trials, maintain highest retention rates possible and acquire high quality data. ..
  49. A NEW GENERATION OF BOTULINUM TOXIN VACCINES
    Md Elias; Fiscal Year: 2009
    ..Therefore, the goal of the proposed work is to develop a mucosal vaccine that will protect vulnerable populations against the use of botulinum toxin as a bioweapon. ..
  50. A novel vaccine: botulinum neurotoxin subunit on a viral carrier.
    Matthias Schnell; Fiscal Year: 2009
    ....
  51. Novel recombinant protein therapeutics of botulism
    David Yang; Fiscal Year: 2003
    b>Botulinum toxins are among the most deadly biological agents with the capacity of mass destruction. The tripartite toxin consists of a receptor binding domain, a membrane translocation domain and a proteolytic catalytic domain...
  52. Botulinum Toxin Effects on Plantar Ulcer Recurrence
    Mary Hastings; Fiscal Year: 2006
    ....
  53. Biocombinatorial Strategies Against Botulinum Toxin
    Kim Janda; Fiscal Year: 2003
    ..The research described provides a foundation for highly sensitive detection and monitoring of BoTox in progenitor and toxic forms and for passive immunotherapy against the active toxin. ..
  54. Polyclonal human antibody in cloned HAC-transgenic cows
    Barbara Osborne; Fiscal Year: 2006
    ..Third, it would provide a new enabling technology for producing clinically important human antibody reagents against other bacterial and viral pathogens. ..
  55. A Novel Immunotoxin for Treatment and Cure of Strabismus
    LEO CHALUPA; Fiscal Year: 2005
    ..The use of IX-146 could be extended in the future to a wider variety of ophthalmologic, neurologic, and neuromuscular disorders, including blepharospasm as well as other types of dystonias. ..
  56. BOTULINUM TOXIN FOR SPASTICITY IN CEREBRAL PALSY
    ROSS HAYS; Fiscal Year: 2001
    ..The large number of assessments required for each patient necessitate that subject enrollment be distributed over the first four and one half years of the study. ..
  57. Motor-Functional Neuroanatomy in Cerebral Palsy
    George Wittenberg; Fiscal Year: 2006
    ..Because the TMS measurements are non-invasive, painless, and relatively rapid, this method has promise for motor general application in understanding, classifying, and treating patients with cerebral palsy. [unreadable] [unreadable]..
  58. FUNCTIONAL ORGANIZATION OF MULTITENDONED FINGER MUSCLES
    Marc Schieber; Fiscal Year: 1999
    ..Moreover, results of the proposed studies of muscles will have broad implications for understanding how finger movements are controlled by the central nervous system. ..
  59. Mechanisms of Neuromuscular Repair by Schwann Cells
    Young Jin Son; Fiscal Year: 2006
    ..Through this work, we attempt to further define the role of Schwann cells in the reactive sprouting and to gain new insights into the inter- and intracellular signaling associated with terminal sprouting. ..
  60. EYELID KINEMATICS IN HEALTH AND DISEASE
    Robert Baker; Fiscal Year: 2001
    ..Taken together, the studies proposed in this application will characterize key aspects of blink adaptive control systems and clarify their adaptive, and potentially maladaptive, roles in disorders of eyelid motility. ..
  61. REGULATION OF MASTICATORY MUSCLE FIBER PHENOTYPE
    ARTHUR ENGLISH; Fiscal Year: 2002
    ..The new knowledge generated will impact significantly several areas of clinical dentistry. ..
  62. Rapid Quality Control Technology for Biodefense Vaccines
    Boris Zaslavsky; Fiscal Year: 2002
    ..b>botulinum toxins, as well as their fragments...
  63. Meeting on the Pathogenesis of Clostridia
    ABRAHAM SONENSHEIN; Fiscal Year: 2003
    ..In addition, toxins produced by the pathogenic Clostridia have become major biodefense concerns, with botulinum toxins and C. perfringens epsilon toxin listed as Class A and B select agents, respectively...
  64. INHIBITORS OF SUBSTRATE ACTIVATED PROTEASES
    DANIEL RICH; Fiscal Year: 2002
    ..This new approach to the design of novel protease inhibitors will be applicable to other substrate activated proteases, many of which function in human biology and are implicated in disease. ..