A5074277057- Amyotrophic Lateral Sclerosis Research
- Teacher Education and Leadership Studies
- Neurogenetic and Muscular Disorders Research
- Education Systems and Policy
- Dysphagia Assessment and Management
- Education and Technology Integration
- Parkinson's Disease Mechanisms and Treatments
- Complement system in diseases
- T-cell and B-cell Immunology
- Online and Blended Learning
- Collaborative Teaching and Inclusion
- Educator Training and Historical Pedagogy
- Global Education and Multiculturalism
- Immunotherapy and Immune Responses
- Pharmacological Receptor Mechanisms and Effects
- Immune Cell Function and Interaction
- Polyomavirus and related diseases
- Botulinum Toxin and Related Neurological Disorders
- Multiple Sclerosis Research Studies
- Renal Transplantation Outcomes and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Viral Infections and Immunology Research
- Alzheimer's disease research and treatments
- Plant Virus Research Studies
- Adenosine and Purinergic Signaling
Center for Neurologic Study
2015-2025
Durham University
2020
California State University System
2019
Southern Cross University
2010-2018
King's College London
2001-2018
Guy's Hospital
2012-2015
King's College Hospital
2015
King's College - North Carolina
2014
Cell Therapy Catapult
2012
Augusta University Health
2012
Mutations in SOD1 cause 13% of familial amyotrophic lateral sclerosis. In the Gly93Ala rat model sclerosis, antisense oligonucleotide ISIS 333611 delivered to CSF decreased mRNA and protein concentrations spinal cord tissue prolonged survival. We aimed assess safety, tolerability, pharmacokinetics after intrathecal administration patients with SOD1-related sclerosis.In this randomised, placebo-controlled, phase 1 trial, we by infusion using an external pump over 11·5 h at increasing doses...
Neurotoxicity from accumulation of misfolded/mutant proteins is thought to drive pathogenesis in neurodegenerative diseases. Since decreasing levels responsible for such accumulations likely ameliorate disease, a therapeutic strategy has been developed downregulate almost any gene the CNS. Modified antisense oligonucleotides, continuously infused intraventricularly, have demonstrated distribute widely throughout CNS rodents and primates, including regions affected major Using this route...
<b><i>Background:</i></b> Patients with ALS commonly exhibit pseudobulbar affect. <b><i>Methods:</i></b> The authors conducted a multicenter, randomized, double-blind, controlled, parallel, three-arm study to test defined combination of dextromethorphan hydrobromide (DM) and quinidine sulfate (Q) (AVP-923) for the treatment affect in ALS. Q inhibits rapid first-pass metabolism DM. effects AVP-923 (30 mg DM plus 30 Q) given twice daily 28 days were compared those its components. evaluated on...
✓ A total of 93 patients with intractable spasticity due to either spinal cord injury (59 cases), multiple sclerosis (31 or other pathology (three cases) were entered into a randomized double-blind placebocontrolled screening protocol intrathecal baclofen test injections. Of the 88 who responded an bolus 50, 75, 100 µg baclofen, 75 underwent implantation programmable pump system for chronic therapy. Patients followed 5 41 months after surgery (mean 19 months). No deaths new permanent...
Significance Direct conversion is a recently established method to generate neuronal progenitor cells (NPCs) from skin fibroblasts in fast and efficient manner. In this study, we show that can be used model neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Because the origin of ALS mainly sporadic with unknown cause, methods disease are urgently needed. The produced NPCs differentiated into astrocytes, which involved motor neuron death ALS. Strikingly, skin-derived...
The development and validation of the Center for Neurologic Study-Lability Scale (CNS-LS), first self report measure affective lability in patients with amyotrophic lateral sclerosis (ALS).Potential questionnaire items were identified through interviews families expert review. Potential items, as well measures affect intensity, psychopathology, depression administered to 99 ALS item selection examination factor structure construct validity. Test-retest reliability was examined using an...
Abstract Objective To evaluate the efficacy and safety of DM/Q (capsules containing dextromethorphan [DM] quinidine [Q]) compared with placebo, taken twice daily, for treatment pseudobulbar affect over a 12‐week period in multiple sclerosis patients. Methods A total 150 patients were randomized double‐blind, placebo‐controlled study to assess validated Center Neurologic Study‐Lability Scale. Each patient also recorded number episodes experienced between visits, estimated quality life...
to the surface of cornea, and inter-connected by scattered oblique anastomoses.Owing triangular shape an antero-posterior section meshwork, only two or three trabecular layers are seen close Descemet's membrane, whereas fifteen twenty present near scleral spur.Rochon-Duvigneaud (1893) described proximal part each layer as resembling a perforated plaque.Asayama(I901) agreed with this description; it is interest note that he suggested possible value studying comparing permeability meshwork on July 23,
The goal of this randomized, blinded, crossover clinical trial was to determine whether Nuedexta (dextromethorphan and quinidine) enhanced speech, swallowing, salivation in patients with ALS. Sixty amyotrophic lateral sclerosis (ALS) received either or placebo for 28 30 days, followed by a 10 15-day washout period. Subsequently, were switched the opposite treatment arm remaining days trial. primary endpoint reduction self-report Center Neurologic Study Bulbar Function Scale (CNS-BFS) score....
IN previous studies of this region (Ashton 1951, 1952), it has been shown that the canal Schlemm and its efferent connections may be clearly demon- strated by Neoprene latex casts, prepared direct injection followed enzyme digestion ocular tissues.Over 200 casts have now studied technique while preparations in main confirm anatomical accounts earlier workers, who used serial sections or injections ink gelatin clearing, they advantage showing exact anatomy entirety a stereoscopic way can...
The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which aging Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions involved tissues, CSF abnormalities reported these conditions are suggestive ChP injury. Indeed, several studies document damage AD, nevertheless remains to be systematically characterized. We here report that changes elicited by AD consistent with a perturbed...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAryldiazirines. Potential reagents for photolabeling of biological receptor sitesRichard A. G. Smith and Jeremy R. KnowlesCite this: J. Am. Chem. Soc. 1973, 95, 15, 5072–5073Publication Date (Print):July 1, 1973Publication History Published online1 May 2002Published inissue 1 July 1973https://pubs.acs.org/doi/10.1021/ja00796a062https://doi.org/10.1021/ja00796a062research-articleACS PublicationsRequest reuse permissionsArticle...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLoop mobility in a four-helix-bundle protein: nitrogen-15 NMR relaxation measurements on human interleukin-4Christina Redfield, Jonathan Boyd, Lorna J. Smith, Richard A. G. and Christopher M. DobsonCite this: Biochemistry 1992, 31, 43, 10431–10437Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November...
After intravenous infusion of recombinant leukocyte interferon (rIFN-αA) to four subjects with an indwelling reservoir, serial serum and cerebrospinal fluid samples were taken over 48 hr analyzed for by enzyme immunoassay method (ELISA). On separate occasions, 18 50 × 106 rIFN-αA infused 10 min. Maximum concentrations ranged from 6720 11,000 pg/ml 32,900 43,400 after the U doses. There was no measurable concentration in who received In three rIFN-αA, 17 70 that earlier than 1 start two cases...
Pseudobulbar affect (PBA) or pathological laughing and crying (PLC) is a disorder of that occurs in about 10% multiple sclerosis (MS) patients. The objective this study was to validate the CNS Emotional Lability Scale (CNS-LS) MS patients correlate results with frequency intensity episodes PLC. Physicians at seven private practice referral centers United States made diagnosis concerning PLC based on patient interviews. Clinical coordinators separately administered CNS-LS, self-report measure...
Pore-forming proteins containing the structurally conserved membrane attack complex/perforin fold play an important role in immunity and host-pathogen interactions. Intermedilysin (ILY) is archetypal member of a cholesterol-dependent cytolysin subclass that hijacks complement receptor CD59 to make cytotoxic pores human cells. ILY directly competes for complex binding site on CD59, rendering cells susceptible lysis. To understand how these bacterial form lipid bilayers plays regulation, we...
Universally established comprehensive clinical bulbar scales objectively assessing disease progression in amyotrophic lateral sclerosis (ALS) are currently lacking. The goal of this working group project is to design a best practice set provisional ALS guidelines, available for immediate implementation within all clinics.ALS specialists across multiple related disciplines participated series symposia, intending identify and summarize the accepted practices assessment management dysfunction...
Alpha-synuclein (α-Syn) oligomers and fibrils have been shown to augment the aggregation of TAR DNA-binding Protein 43 (TDP-43) monomers in vitro, supporting idea that TDP-43 proteinopathies such as ALS may be modulated by presence toxic forms α-Syn. Recently, parkinsonian features were reported a study European patients Lewy bodies demonstrated pathologically similar series patients. Based on these other considerations, we sought determine whether seed-competent α-Syn can identified spinal...
There has been a substantial amount of interest in the anticonvulsant and neuroprotective actions dextromethorphan. Its therapeutic efficacy, however, is limited by its extensive first-pass elimination way cytochrome P4502D6 enzyme humans. The purpose this research was to determine whether quinidine (a selective inhibitor P4502D6) could improve dextromethorphan systemic delivery patients with amyotrophic lateral sclerosis neurodegenerative disease). In absence quinidine, 60 mg every 12 hours...