A5083921697- Prion Diseases and Protein Misfolding
- Monoclonal and Polyclonal Antibodies Research
- Neurological diseases and metabolism
- Trace Elements in Health
- T-cell and B-cell Immunology
- RNA regulation and disease
- Immunodeficiency and Autoimmune Disorders
- Virology and Viral Diseases
- Virus-based gene therapy research
- Respiratory viral infections research
- Herpesvirus Infections and Treatments
- Ear Surgery and Otitis Media
- Cytomegalovirus and herpesvirus research
- Vestibular and auditory disorders
- HIV Research and Treatment
- Immunotherapy and Immune Responses
- Ear and Head Tumors
- Avian ecology and behavior
- Glycosylation and Glycoproteins Research
- Bacteriophages and microbial interactions
- Diabetes and associated disorders
- Biotin and Related Studies
- Hearing, Cochlea, Tinnitus, Genetics
- Multiple Sclerosis Research Studies
- Cerebral Venous Sinus Thrombosis
Zygo (United States)
2023
Williamson College
2023
Janssen (United Kingdom)
2017-2018
Johnson & Johnson (United Kingdom)
2017-2018
Health Foundation
2018
Johnson & Johnson (Israel)
2018
Janssen (Belgium)
2018
University of Arizona
2017
Ascension
2016
Baylor College of Medicine
2003-2014
Neuronal death is a prominent, but poorly understood, pathological hallmark of prion disease. Notably, in the absence cellular protein (PrPC), disease-associated isoform, PrPSc, appears not to be intrinsically neurotoxic, suggesting that PrPC itself may participate directly neurodegenerative cascade. Here, cross-linking vivo with specific monoclonal antibodies was found trigger rapid and extensive apoptosis hippocampal cerebellar neurons. These findings suggest functions control neuronal...
Abstract Studies of prion biology and diseases have elucidated several new concepts, but none was more heretical than the proposal that biological properties distinguish different strains are enciphered in disease‐causing protein (PrP Sc ). To explore this postulate, we examined PrP from eight isolates propagate Syrian hamster (SHa). Using resistance to protease digestion as a marker for undenatured protein, conformational stabilities these molecules. All showed sigmoidal patterns transition...
To understand the posttranslational conversion of cellular prion protein (PrPC) to its pathologic conformation, it is important define intracellular trafficking pathway PrPC within endomembrane system. We studied localization and internalization in CHO cells using cryoimmunogold electron microscopy. At steady state, was enriched caveolae both at TGN plasma membrane interconnecting chains endocytic caveolae. Protein A-gold particles bound specifically on live cells. These complexes were...
Abstract Single-cell RT-PCR was used to sample CD19+ B cell repertoires in cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) or viral meningitis. Analysis amplified Ab H and L chain products served identify the rearranged germline segment J segment, determine degree homology for sequence individual cells. The repertoire meningitis CSF predominately polyclonal, whereas clonal expansion a prominent feature IgG three four MS patients. Two dominant populations one accounted ∼70%...
ABSTRACT The fundamental event in prion disease is thought to be the posttranslational conversion of cellular protein (PrP C ) into a pathogenic isoform Sc ). occurrence PrP on cell surface and amyloid plaques situ or aggregates following purification complicates study molecular events that underlie process. Monoclonal antibodies are highly sensitive probes conformation which can used under these conditions. Here, we report rescue diverse panel 19 PrP-specific recombinant monoclonal from...
Localizing the cellular prion protein (PrPC) in brain is necessary for understanding pathogenesis of diseases. However, precise ultrastructural localization PrPC still remains enigmatic. We performed first quantitative study mouse hippocampus using high-resolution cryoimmunogold electron microscopy. follows standard biosynthetic trafficking pathway with a preferential late endosomal compartments and on plasma membrane neurons neuronal processes. found same frequency within synaptic...
To present an updated version of the original Facial Nerve Grading Scale (FNGS), commonly referred to as House-Brackmann scale.Controlled trial grading systems using a series 21 videos individuals with varying degrees facial paralysis.The intraobserver and interobserver agreement was high among revised scales. Nominal improvement is seen in percentage exact grade reduction instances examiners differing by more then one when FNGS 2.0. 2.0 also offers improved differentiating between grades 3...
Little is currently known about the biochemical mechanism by which induced prion protein (PrP) conformational change occurs during mammalian propagation. In this study, we describe reconstitution of PrPres amplification <i>in vitro</i> using partially purified and synthetic components. Overnight incubation PrP27–30 PrP<sup>C</sup> molecules at a molar ratio 1:250 yielded ∼2-fold baseline amplification. Addition various polyanionic increased level to ∼10-fold overall. Polyanionic compounds...
Abstract Objective Intrathecal IgG synthesis, persistence of bands oligoclonal IgG, and memory B‐cell clonal expansion are well‐characterized features the humoral response in multiple sclerosis (MS). Nevertheless, target antigen this remains enigmatic. Methods We produced 53 different human IgG1 monoclonal recombinant antibodies (rAbs) by coexpressing paired heavy‐ light‐chain variable region sequences 51 plasma cell clones 2 B‐lymphocyte from MS cerebrospinal fluid tissue culture cells....
Diagnosis of transmissible spongiform encephalopathy (TSE) disease in humans and ruminants relies on the detection post-mortem brain tissue protease-resistant form host glycoprotein PrP. The presence this abnormal isoform (PrP(Sc)) tissues is taken as indicative TSE infectivity. Here we demonstrate conclusively that high titers infectivity can be present animals show clinical vacuolar signs but contain low or undetectable levels PrP(Sc). This work questions correlation between PrP(Sc) level...
Objective To quantify the association between patient self-management capability measured using Patient Activation Measure (PAM) and healthcare utilisation across a whole health economy. Results 12 270 PAM questionnaires were returned from 9348 patients. In adjusted analyses, compared with least activated group, highly patients (level 4) had lowest rate of contact general practitioner (rate ratio: 0.82, 95% CI 0.79 to 0.86), emergency department attendances 0.68, 0.60 0.78), hospital...
The early-life intestinal microbiota plays a key role in shaping host immune system development. We found that single antibiotic course (1PAT) accelerated type 1 diabetes (T1D) development male NOD mice. had deep and persistent effects on the microbiome, leading to altered cecal, hepatic, serum metabolites. exposure elicited sex-specific chromatin states ileum liver perturbed ileal gene expression, altering normal maturational patterns. global signature changes included specific genes...
Conventional antibody generation usually requires active immunization with antigen immediately prior to the preparation procedure. Combinatorial library technology offers possibility of cloning a range specificities at single point in time and then accessing these will. Here we show that human monoclonal Fab fragments against plethora infectious agents can be readily derived from library. Further examination number libraries shows whenever pathogen detected serum donor, specific antibodies...
The relatively new clinical entity superior canal dehiscence syndrome (SCDS) is diagnosed by symptoms and signs. Coronal computed tomography (CT) has been used to confirm the diagnosis. A consecutive series of temporal bone CT scans was reviewed define prevalence a dehiscent-appearing semicircular canal.Temporal performed over 2-year period at university-based tertiary referral center were independently 3 individuals. Scans excluded if coronal images not obtained or reconstructed from axial...
Previously, recombinant human respiratory syncytial virus (RSV) monoclonal antibody Fabs were generated by antigen selection from random combinatorial libraries displayed at the tip of filamentous phage. Two such Fabs, which exhibited high binding affinity for RSV F glycoprotein (a major protective antigen), evaluated therapeutic efficacy in infected mice just before or time peak replication lungs. Fab 19, neutralized infectivity with efficiency tissue culture, was effective therapeutically...
The central pathogenic event of prion disease is the conformational conversion a host protein, PrPC, into isoform, PrPSc. We previously showed that protein misfolding cyclic amplification (PMCA) technique can be used to form infectious molecules de novo from purified native PrPC in an autocatalytic process requiring accessory polyanions (Deleault, N. R., Harris, B. T., Rees, J. and Supattapone, S. (2007) Proc. Natl. Acad. Sci. U. A. 104, 9741-9746). Here we investigated molecular mechanism...
To review the presentation and management of improper electrode array placement, to help guide clinical decision-making.Retrospective case series.Pediatric adult cochlear implant patients managed from January 2001 present whose arrays were not placed properly within cochlea or extended beyond into internal auditory canal adjacent structures.Four patients, three pediatric one adult, identified over 824 cases (< 1%) study duration. All had normal anatomy. These initially due poor skill...
Human metapneumovirus (HMPV) is a leading cause of acute respiratory tract infection, with significant morbidity and mortality. No licensed vaccines or therapeutic agents exist. Monoclonal antibodies (mAbs) are effective at preventing other infectious diseases could be used against HMPV in high-risk hosts.In vitro assays were performed to assess the neutralizing activity affinity kinetics human mAb 54G10. A new mouse model was developed prophylactic efficacy vivo. The epitope 54G10...