A5027349211- Pain Mechanisms and Treatments
- Peripheral Neuropathies and Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Traumatic Brain Injury and Neurovascular Disturbances
- Myasthenia Gravis and Thymoma
- Peripheral Nerve Disorders
- Viral Infections and Immunology Research
- Nerve injury and regeneration
- interferon and immune responses
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- Hereditary Neurological Disorders
- Botulinum Toxin and Related Neurological Disorders
- Barrier Structure and Function Studies
- RNA regulation and disease
- Multiple Sclerosis Research Studies
- Plant and Biological Electrophysiology Studies
- Anesthesia and Neurotoxicity Research
- Neurological Disorders and Treatments
- Adipose Tissue and Metabolism
- Neuroscience, Education and Cognitive Function
- Caveolin-1 and cellular processes
- Eicosanoids and Hypertension Pharmacology
- Neurological diseases and metabolism
- Autoimmune Neurological Disorders and Treatments
Kingston University
2023
University of California, San Diego
1997-2015
University of Pittsburgh
2009
Colby College
2009
United States Department of Veterans Affairs
1988-1999
Scripps Research Institute
1995-1998
University of San Diego
1998
University of Gothenburg
1988
La Jolla Alcohol Research
1986
University of California San Diego Medical Center
1982-1983
Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system mediated by CD4+ T cells reactive with myelin basic protein (MBP). Rats were rendered resistant to induction EAE vaccination synthetic peptides corresponding idiotypic determinants beta chain VDJ region and J alpha regions cell receptor (TCR) that are conserved among encephalitogenic cells. These findings demonstrate utility TCR peptide for modulating activity autoreactive represent a general...
As both astrocytes and cytokines modulate the permeability of cerebral endothelial cells, transgenic animal models which overexpress cytokines, such as interleukin-6 (IL-6), may provide insight into neuropathological consequences increased BBB permeability. In this study, a GFAP-IL6 mouse model horseradish peroxidase (HRP) were used to investigate associated neuropathologic changes. cerebellum control mice, developed between postnatal days 7 14. never extensive breakdown was evident in high-...
Abstract Type I IFNs, which include IFN-α, appear to have complex and broad-ranging actions in the central nervous system (CNS) that may result protection or injury. To better understand these issues, we generated transgenic mice produce IFN-α1 chronically from astrocytes. These glial fibrillary acidic protein-IFN-α developed a progressive inflammatory encephalopathy, with marked calcium mineralization, meninoencephalitis, gliosis, neurodegeneration. Many features of this murine...
Spinal nerve roots including the dorsal root ganglion (DRG) often are mechanically deformed in connection with degenerative and traumatic conditions of spine. However, pathophysiology underlying various functional changes, pain production, such is incompletely known. In this study, tissue fluid pressure DRG L5 rats was measured before after compression. Normal values were found to be 3.7 ± 0.3 cm H2O (2.7 0.2 mm Hg). After mechanical compression, endoneurial ganglia rose 9.6 1.7 (7.1 1.2 Hg)...
Based on previous work, we hypothesized that activation of spinal NMDA-receptor initiates the p38 mitogen-activated protein kinase (p38 MAPK) pathway, leading to release prostaglandins and hyperalgesia. Accordingly, examined effect intrathecal SD-282, a selective MAPK inhibitor, NMDA-induced prostaglandin E2 (PGE2) thermal Inhibition attenuated both NMDA-evoked PGE2 NMDA injection led increased phospho-p38 immunoreactivity in superficial (I–II) dorsal laminae. Co-labeling studies revealed...
Abnormal humoral responses toward motor end plate constituents in muscle induce myasthenia gravis (MG). To study the etiology of this disease, and whether it could be induced by host defense molecules, we examined consequences interferon (IFN) gamma production within neuromuscular junction transgenic mice. The mice exhibited gradually increasing muscular weakness, flaccid paralysis, functional disruption that was reversed after administration an inhibitor acetylcholinesterase, features which...
Abstract Antagonist studies show that spinal p38 mitogen‐activated protein kinase plays a crucial role in sensitization. However, there are two isoforms found cord and the relative contribution of these to hyperalgesia is not known. Here we demonstrate distinctly expressed dorsal horn: p38α neurons p38β microglia. In lieu isoform selective inhibitors, examined functional individual nociception by using intrathecal isoform‐specific antisense oligonucleotides selectively block expression...
Activated macrophage/microglia may mediate tissue injury in a variety of CNS disorders. To examine this, transgenic mice were developed which the expression activation cytokine, interleukin-3 (IL-3), was targeted to astrocytes using murine glial fibrillary acidic protein fusion gene. Transgenic with low levels IL-3 from 5 mo age, progressive motor disorder characterized at onset by impaired rota-rod performance. In symptomatic mice, multi-focal, plaque-like white matter lesions present...
Streptococcus iniae represents a major health and economic problem in fish species worldwide. Random Tn917 mutagenesis high-throughput screening hybrid striped bass (HSB) model of meningoencephalitis identified attenuated S. mutants. The insertion one mutant disrupted an homologue phosphoglucomutase (pgm) gene. Electron microscopy revealed decrease capsule thickness cell wall rigidity, with DeltaPGM cells reaching sizes approximately 3-fold larger than those the wild type (WT). was cleared...
Abstract Objective Because articular chondrocytes reside in a hypoxic milieu, anaerobic glycolysis is central generating ATP to support chondrocyte matrix synthesis and viability, with mitochondrial oxidative phosphorylation possibly providing physiologic reserve generation. Nitric oxide (NO) potently suppresses phosphorylation. enhanced cartilage NO generation occurs osteoarthritis (OA), we systematically tested for dysfunction the pathogenesis of OA. Methods We assessed depletion situ...
Nerve biopsy is often the final step in diagnostic work‐up of neuropathies unknown origin. The aim this guideline was to prepare an evidence‐based on methods for performing and evaluating nerve biopsy. panel performed a search MEDLINE, hand bibliographies references retrieved, review evidence, reached agreement by consensus. There were not enough formal studies test accuracy allow recommendations levels A–C most questions. summarized class IV evidence consensus following recommendations: (1)...
Clinical and morphologic findings from two patients with Progressive Supranuclear Palsy (PSP) are discussed compared observations in postencephalitic Parkinsonism. The most severely affected regions of the brain PSP included subthalamic, vestibular, dentate nuclei addition to those usually involved Birefringent neurofibrillary tangles were found degenerating neurons. Electron microscopy showed juxtaneuronal Hirano bodies, electron-dense, membrane-bound, spheroid particles within composed...
To test the hypothesis that increased endoneurial fluid pressure (EFP) causes a reduction in nerve blood flow (NBF) vasa nervorum, we adapted noninvasive method for measurement of which was originally developed local cerebral flow. This technique measures tissue distribution radioisotope, 14C-iodoantipyrine, and used to compare NBF sciatic nerves rats with EFP induced by feeding them hexachlorophene (HCP), neurotoxin edema exclusively nervous system confined myelin sheath. Elevation...
Symptomatic neuropathy is a common manifestation of diabetes mellitus, and sensory, motor, or autonomic symptoms occur in approximately 10% all diabetic patients. Animal models may be useful to study the metabolic electrophysiologic abnormalities peculiar neuropathy. Genetic animal models, including Chinese hamster, ob/ob mouse, db/db BB-wistar rat, SSDR rat chemically induced nutritional mellitus provide potential use animals human neuropathy; however, date, few characteristics have been...
Background— PINCH proteins are 5 LIM domain–only adaptor that function as key components of the integrin signaling pathway and play crucial roles in multiple cellular processes. Two proteins, PINCH1 PINCH2, have been described mammals share high homology. Both PINCH2 ubiquitously expressed most tissues organs, including myocardium. Cardiac-specific knockout or global mice exhibit no basal cardiac phenotype, which may reflect a redundant role for these 2 A potential myocardium remains...
A new technique has been developed for the microanalysis of interstitial fluid from peripheral nerve. Energy dispersive spectrometry (EDS) was employed to measure X-ray fluorescence secondary electron excitation endoneurial in order determine concentration sodium, chloride, and potassium 100 picoliter samples collected situ. Normal Long-Evans (L-E) rats had electrolyte values which were higher than serum explained positive pressure nerve interstitium. Ten weeks after starting a diet...