A5060850766- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Prion Diseases and Protein Misfolding
- Diabetes Management and Research
- Pericarditis and Cardiac Tamponade
- Metabolism and Genetic Disorders
- Neurological disorders and treatments
- Hereditary Neurological Disorders
- Diabetes Treatment and Management
- Diabetes and associated disorders
- Protein Degradation and Inhibitors
- Chronic Myeloid Leukemia Treatments
- Health and Medical Research Impacts
- Pancreatic function and diabetes
- Acute Myeloid Leukemia Research
- Ion channel regulation and function
- Pharmacology and Obesity Treatment
- Porphyrin Metabolism and Disorders
- Infective Endocarditis Diagnosis and Management
- Pleural and Pulmonary Diseases
- Cytomegalovirus and herpesvirus research
- Cardiac tumors and thrombi
- Medical History and Innovations
- RNA regulation and disease
National Institute for Biological Standards and Control
2007-2024
Thomas Jefferson University Hospital
2019-2023
Johns Hopkins Medicine
1998-2007
Johns Hopkins University
1998-2007
Niigata University
2003
Institute of Neurobiology
2001
Expanded polyglutamine repeats have been proposed to cause neuronal degeneration in Huntington's disease (HD) and related disorders, through abnormal interactions with other proteins containing short tracts such as the transcriptional coactivator CREB binding protein, CBP. We found that CBP was depleted from its normal nuclear location present aggregates HD cell culture models, transgenic mice, human postmortem brain. specifically interfere CBP-activated gene transcription, overexpression of...
Expansion of a polyglutamine sequence in the N terminus huntingtin is gain-of-function event that causes Huntington's disease. This mutation affects primarily medium-size spiny neurons striatum. Huntingtin expressed many neuronal and non-neuronal cell types, implying more general function for wild-type protein. Here we report acts by protecting CNS cells from variety apoptotic stimuli, including serum withdrawal, death receptors, pro-apoptotic Bcl-2 homologs. protection may take place at...
Huntington's disease (HD) is a progressive neurodegenerative disorder caused by an expanding CAG repeat coding for polyglutamine in the huntingtin protein. Recent data have suggested possibility that N-terminal fragment of may aggregate neurons patients with HD, both cytoplasm, forming dystrophic neurites, and nucleus, intranuclear neuronal inclusion bodies. An animal model HD using short has also been found to inclusions this same can vitro. We now developed cell culture demonstrating...
Huntington's disease is a neurodegenerative disorder resulting from expansion of the polyglutamine region in huntingtin. Although huntingtin normally cytoplasmic, affected brain regions proteolytic fragments mutant containing repeat form intranuclear inclusions. Here, we examine contribution nuclear localization to toxicity by transiently transfecting neuro-2a cells with an N-terminal fragment similar size that believed be present patients. The fragment, HD-N63, was targeted either cytoplasm...
Dentatorubral and pallidoluysian atrophy (DRPLA) is a member of family progressive neurodegenerative diseases caused by polyglutamine repeat expansion. Transgenic mice expressing full-length human atrophin-1 with 65 consecutive glutamines exhibit ataxia, tremors, abnormal movements, seizures, premature death. These accumulate immunoreactivity inclusion bodies in the nuclei multiple populations neurons. Subcellular fractionation revealed 120 kDa nuclear fragments mutant atrophin-1, whose...
Huntington disease (HD) is caused by the expansion of a glutamine (Q) repeat near N terminus huntingtin (htt), resulting in altered conformation mutant protein to produce, most prominently brain neurons, nuclear and cytoplasmic inclusion pathology. The inclusions associated diffuse accumulation htt nuclei are composed N-terminal fragments protein. Here, we used panel peptide antibodies characterize pathologies tissues from human HD, transgenic mouse model created expressing first 171 amino...
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of a polyglutamine tract in huntingtin protein. We have developed PC12 cell lines which expression N-terminal truncation (N63) with either wild type (23Q) or expanded (148Q) can be induced removal doxycycline. Differentiated cells to express N63-148Q showed cellular toxicity reaching up 50% at 6 days post-induction. Histone acetyltransferase (HAT) activity and global histone...
Background and Objectives With four transfusion related transmissions of variant Creutzfeldt–Jakob Disease (vCJD), three which developed clinical disease the other died causes but was positive for markers infection, there is an increased urgency to identify implement a test blood donor screening. limited amounts samples from vCJD cases available evaluation challenging. Alternative approaches are therefore needed. Control tissues homogenates, where levels infectivity known, were sequentially...
Background and Objectives Evaluation of variant C reutzfeldt– J akob disease ( vCJD ) diagnostic/donor screening tests is made complicated by the very limited supply blood samples from clinically confirmed cases . To determine appropriate access for test developers to rare CJD samples, oversight committee NIBSC Resource Centre has developed a process protocols detailing minimum requirements both sensitivity specificity. This protocol broadly similar that outlined in common technical...
A patient presents with pleuritic chest pain, dyspnea, and a recent viral illness. They have no prior cardiac or pulmonary history. Their X-ray on admission demonstrates findings an enlarged silhouette, their EKG is low voltage electrical alternans. Ultrasound effective modality for identifying pericardial effusion tamponade while at the same time evaluating other causes, such as heart failure. Often patients symptomatic ef fusion present non-specific symptoms. While “formal” transthoracic...
Background and Objectives A standard panel of materials is needed for the evaluation assays being developed diagnosis variant Creutzfeldt–Jakob disease. Materials Methods Tissues from human animals incubating transmissible spongiform encephalopathy disease have been prepared, aliquoted where possible characterized by in vitro methods. Results standardized preparation has generated. Conclusions Large‐scale preparations tissues blood fractions can be used to directly compare sensitivities...
t(8;21)(q22;q22) is present in ~5-10% of patients with de novo acute myeloid leukemia (AML) and associated a better overall prognosis. Variants the t(8;21) have been described literature, however, their clinical prognostic significance has not well-characterized. Molecular profiling these cases previously reported but may be useful defining prognosis this subset patients. We two variant AML including clinical, cytogenetic, molecular data.
Introduction: Gastrointestinal (GI) malignancies are associated with paraneoplastic sequelae such as non-bacterial thrombotic endocarditis (NBTE) and inflammatory myopathy. We describe a unique case in which metastatic gastric malignancy presented without typical GI symptoms instead was discovered after pursuing unifying diagnosis for constellation of cardiac, neurologic, musculoskeletal manifestations. Case Description/Methods: A 61-year-old woman to tertiary medical center shoulder thigh...
It is our honor to present the product of 22 years resident-run tradition – 2020-2021 annual edition The Medicine Forum. In world Jefferson traditions, ours a small one. There no regalia, pomp and circumstance, or any such fanfare in this marking year’s close. Rather than celebratory release those other springtime occasions, publication representation yearlong dedication hard work residents fellows their academic pursuits.