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Search Results: 1 - 10 of 462227 matches for " Holly A. Shill "
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Emerging Therapies for the Treatment of Essential Tremor
Holly A. Shill
Clinical Medicine : Therapeutics , 2009,
Abstract: This article will review newer therapies for the treatment of essential tremor as well as cover potential therapies still in development. Drug pharmacology, specific dosing for ET and adverse effects will be reviewed. Finally, a rationale approach to treatment of ET will be discussed.
Update on ropinirole in the treatment of Parkinson’s disease
Holly A Shill, Mark Stacy
Neuropsychiatric Disease and Treatment , 2009, DOI: http://dx.doi.org/10.2147/NDT.S3237
Abstract: ate on ropinirole in the treatment of Parkinson’s disease Review (7084) Total Article Views Authors: Holly A Shill, Mark Stacy Published Date December 2008 Volume 2009:5 Pages 33 - 36 DOI: http://dx.doi.org/10.2147/NDT.S3237 Holly A Shill, Mark Stacy Sun Health Research Institute, Sun City, AZ, USA; Duke University and Medical Center, Durham, NC, USA Abstract: Ropinirole is a dopamine agonist, approved for use to treat symptoms of early and advanced Parkinson’s disease, is now available in a 24-hour formulation in addition to the immediate release version. This review discusses the mode of action of ropinirole and compares the pharmacokinetics of both formulations. Pivotal studies leading to the approval of both preparations are reviewed in terms of efficacy, dose range and side effects. Patient factors such as compliance are discussed in terms of the place for ropinirole in the armamentarium of Parkinson’s disease therapies.
Update on ropinirole in the treatment of Parkinson’s disease
Holly A Shill,Mark Stacy
Neuropsychiatric Disease and Treatment , 2008,
Abstract: Holly A Shill, Mark StacySun Health Research Institute, Sun City, AZ, USA; Duke University and Medical Center, Durham, NC, USAAbstract: Ropinirole is a dopamine agonist, approved for use to treat symptoms of early and advanced Parkinson’s disease, is now available in a 24-hour formulation in addition to the immediate release version. This review discusses the mode of action of ropinirole and compares the pharmacokinetics of both formulations. Pivotal studies leading to the approval of both preparations are reviewed in terms of efficacy, dose range and side effects. Patient factors such as compliance are discussed in terms of the place for ropinirole in the armamentarium of Parkinson’s disease therapies.Keywords: ropinirole extended release, ropinirole immediate release Parkinson’s disease
Essential Tremor in the Elderly and Risk for Dementia
Holly A. Shill,Joseph G. Hentz,Sandra A. Jacobson,Christine Belden,Marwan N. Sabbagh,Thomas G. Beach,Erika Driver-Dunckley,Charles H. Adler
Journal of Neurodegenerative Diseases , 2014, DOI: 10.1155/2014/328765
Abstract: The objective is to examine the risk of dementia in subjects with essential tremor (ET) involved in the Arizona Study of Aging and Neurodegenerative Disorders. All subjects were free of a neurodegenerative diagnosis at baseline and had annual motor, general neurological, and neuropsychological assessments. Subjects with ET were compared with controls for the risk of dementia. There were 83 subjects with ET and 424 subjects without tremor. Mean age at study entry was for ET and for controls. Median tremor duration was 5.2 years at study entry. Followup was a median of 5.4 years (range 0.9 to 12.1). The hazard ratio for the association between ET and dementia was 0.79 (95% CI 0.33 to 1.85). The hazard ratio for the association between tremor onset at age 65 or over, versus onset before age 65, was 2.1 (95% CI 0.24 to 18) and the hazard ratio for the association between tremor duration greater than 5 years, versus less than 5 years, was 0.46 (95% CI 0.08 to 2.6). We conclude that all elderly ET was not associated with an increased risk of dementia but that a subset of subjects with older age onset/shorter duration tremor may be at higher risk. 1. Introduction Essential tremor (ET) is a common neurological condition which increases with the age of the population and contributes to significant disability in most affected patients. Previous cross-sectional studies have shown that patients with ET may have minor cognitive deficits on formal testing although most of these older studies have been done with advanced ET patients being assessed for deep brain stimulation as treatment for tremor [1, 2]. More recently, a population study of ET demonstrated that more mildly affected, largely untreated ET individuals may be more likely to complain of memory problems and have deficits at testing [3]. This same population was more likely to have prevalent dementia, largely driven by elderly onset ET [4]. In those nondemented at baseline, incident dementia was greater in ET [5]. This study seeks to compare the risk of developing dementia in subjects with ET versus controls without tremor in a large, well-categorized cohort of individuals involved in a longitudinal aging study, the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). 2. Methods Participants without dementia or another neurodegenerative disorder at study entry and who had at least one follow-up visit were selected from the 23 May 2013 version of the AZSAND database which included 3300 subjects. All participants, both cases and controls, were initially recruited into the study largely as a result
Quantitative Appraisal of Ventricular Cerebrospinal Fluid Biomarkers in Neuropathologically Diagnosed Parkinson's Disease Cases Lacking Alzheimer's Disease Pathology
Chera L. Maarouf, Thomas G. Beach, Charles H. Adler, Michael Malek-Ahmadi, Tyler A. Kokjohn, Brittany N. Dugger, Douglas G. Walker, Holly A. Shill, Sandra A. Jacobson, Marwan N. Sabbagh, Alex E. Roher and Arizona Parkinson’s Disease Consortium
Biomarker Insights , 2012, DOI: 10.4137/BMI.S11422
Abstract: Identifying biomarkers that distinguish Parkinson’s disease (PD) from normal control (NC) individuals has the potential to increase diagnostic sensitivity for the detection of early-stage PD. A previous proteomic study identified potential biomarkers in postmortem ventricular cerebrospinal fluid (V-CSF) from neuropathologically diagnosed PD subjects lacking Alzheimer’s disease (AD) neuropathology. In the present study, we assessed these biomarkers as well as p-tau181, Aβ42, and S100B by ELISA in PD (n = 43) and NC (n = 49) cases. The p-tau181/A 42 ratio and ApoA-1 showed statistically significant differences between groups. Multiple regression analysis demonstrated that p-tau181/Aβ42 had a significant odds ratio: OR = 1.42 (95% confidence interval [CI], 1.12–1.84), P = 0.006. Among the molecules investigated, intriguing correlations were observed that require further investigation. Our results suggest co-existent AD CSF biomarkers within the PD group notwithstanding that it was selected to minimize AD neuropathological lesions.
SMG1 Identified as a Regulator of Parkinson’s Disease-Associated alpha-Synuclein through siRNA Screening
Adrienne Henderson-Smith, Donald Chow, Bessie Meechoovet, Meraj Aziz, Sandra A. Jacobson, Holly A. Shill, Marwan N. Sabbagh, John N. Caviness, Charles H. Adler, Erika D. Driver-Dunckley, Thomas G. Beach, Hongwei Yin, Travis Dunckley
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0077711
Abstract: Synucleinopathies are a broad class of neurodegenerative disorders characterized by the presence of intracellular protein aggregates containing α-synuclein protein. The aggregated α-synuclein protein is hyperphosphorylated on serine 129 (S129) compared to the unaggregated form of the protein. While the precise functional consequences of S129 hyperphosphorylation are still being clarified, numerous in vitro and in vivo studies suggest that S129 phosphorylation is an early event in α-synuclein dysfunction and aggregation. Identifying the kinases and phosphatases that regulate this critical phosphorylation event may ultimately prove beneficial by allowing pharmacological mitigation of synuclein dysfunction and toxicity in Parkinson’s disease and other synucleinopathies. We report here the development of a high-content, fluorescence-based assay to quantitate levels of total and S129 phosphorylated α-synuclein protein. We have applied this assay to conduct high-throughput loss-of-function screens with siRNA libraries targeting 711 known and predicted human kinases and 206 phosphatases. Specifically, knockdown of the phosphatidylinositol 3-kinase related kinase SMG1 resulted in significant increases in the expression of pS129 phosphorylated α-synuclein (p-syn). Moreover, SMG1 protein levels were significantly reduced in brain regions with high p-syn levels in both dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD). These findings suggest that SMG1 may play an important role in increased α-synuclein pathology during the course of PDD, DLB, and possibly other synucleinopathies.
The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's disease: the GenePD study
Jeanne C Latourelle, Mei Sun, Mark F Lew, Oksana Suchowersky, Christine Klein, Lawrence I Golbe, Margery H Mark, John H Growdon, G Frederick Wooten, Ray L Watts, Mark Guttman, Brad A Racette, Joel S Perlmutter, Anwar Ahmed, Holly A Shill, Carlos Singer, Stefano Goldwurm, Gianni Pezzoli, Michela Zini, Marie H Saint-Hilaire, Audrey E Hendricks, Sally Williamson, Michael W Nagle, Jemma B Wilk, Tiffany Massood, Karen W Huskey, Jason M Laramie, Anita L DeStefano, Kenneth B Baker, Ilia Itin
BMC Medicine , 2008, DOI: 10.1186/1741-7015-6-32
Abstract: A sample, including 903 affected and 58 unaffected members from 509 families ascertained for having two or more PD-affected members, 126 randomly ascertained PD patients and 197 controls, was screened for five different LRRK2 mutations. Penetrance was estimated in families of LRRK2 carriers with consideration of the inherent bias towards increased penetrance in a familial sample.Thirty-one out of 509 families with multiple cases of PD (6.1%) were found to have 58 LRRK2 mutation carriers (6.4%). Twenty-nine of the 31 families had G2019S mutations while two had R1441C mutations. No mutations were identified among controls or unaffected relatives of PD cases. Nine PD-affected relatives of G2019S carriers did not carry the LRRK2 mutation themselves. At the maximum observed age range of 90 to 94 years, the unbiased estimated penetrance was 67% for G2019S families, compared with a baseline PD risk of 17% seen in the non-LRRK2-related PD families.Lifetime penetrance of LRRK2 estimated in the unascertained relatives of multiplex PD families is greater than that reported in studies of sporadically ascertained LRRK2 cases, suggesting that inherited susceptibility factors may modify the penetrance of LRRK2 mutations. In addition, the presence of nine PD phenocopies in the LRRK2 families suggests that these susceptibility factors may also increase the risk of non-LRRK2-related PD. No differences in penetrance were found between men and women, suggesting that the factors that influence penetrance for LRRK2 carriers are independent of the factors which increase PD prevalence in men.Parkinson's disease (PD) is a neurodegenerative disorder, affecting approximately 1.8% of individuals over the age of 65 [1]. Some cases of PD are due to known genetic or environmental factors but most are likely due to complex interactions among unidentified genes and environmental risk factors. These susceptibility factors may also play a role in the penetrance of known PD genes.Mutations in the leuc
Anti-Inflammatory, Diuretic and Antibacterial Activities of Aerial Parts of Mucuna pruriens Linn.
V. Bala,A. Debnath,A.K. Shill,U. Bose
International Journal of Pharmacology , 2011,
Abstract: The ethanolic extract of the dried aerial parts of Mucuna pruriens Linn. (Fabaceae) was investigated for its possible anti-inflammatory, diuretic and antibacterial activities in animal models. Anti-inflammatory activity was tested using carrageenin induced rat paw edema model and cotton pellet implantation method in rat. Diuretic activity was measured by the comparison of control group, standard drug group (furosemide) at a dose of 0.5 mg kg-1 and the sample extracts 200 and 400 mg kg-1, respectively. The antibacterial property was studied by the disc diffusion method using extract 200 mg disc-1. The extracts significantly (p<0.001) reduced carrageenin induced paw edema in rats. Cotton pellet implantation model for antiinflammatory activity, the extract showed a significant reduction in the weight of the cotton pellet in test animal compared to control (p<0.001). At the doses of 200 and 400 mg kg-1, the extract exhibited 24.59 and 33.41% reduction of the weight of the cotton pellets. Diuretic activity was proved by the electrolyte loss ratio (Na+/K+ excretion ratio was 1.48 and 1.45 at the doses of 200 and 400 mg kg-1, respectively) as that of the standard diuretic furosemide (1.47). The extracts also showed the antibacterial activity against eight species of bacteria. The results obtained shows that the extracts of Mucuna pruriens Linn. has anti-inflammatory, diuretic and antibacterial properties. This finding provides a basis for the traditional use of the plant material.
Ensembles of Artificial Example based Neural Networks
M. A. H. Akhand,P. C. Shill,K. Murase
Journal of Computers , 2010, DOI: 10.4304/jcp.5.12.1819-1827
Abstract: Ensembles with several neural networks are widely used to improve the generalization performance over a single network. A proper diversity among component networks is considered as an important parameter for ensemble construction so that the failure of one may be compensated by others. Data sampling, i.e., different training sets for different networks, is the most investigated technique for diversity than other approaches. This paper presents a data sampling based neural network ensemble method where the individual networks are trained on the union of original training set and a set of some artificially generated examples. Generated examples are different for different networks and are the element to produce diversity among the networks. After each network is trained, the method checks whether the trained network is suitable to ensemble or not, and absorbs the network based on the ensemble performance with it. The effectiveness of the method is evaluated on a suite of 20 benchmark classification problems. The experimental results show that the performance of this ensemble method is better or competitive with respect to the existing popular methods.
Disassembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients
Zhenyu Zhong, Hikmet Nural, Ping He, Gina Civarella, Thomas Beach, Lucia Sue, Charles Adler, Holly Shill, John Caviness, Weiming Xia, Yong Shen
Molecular Neurodegeneration , 2009, DOI: 10.1186/1750-1326-4-30
Abstract: After publication of this work [1], we noted that we inadvertently failed to include the complete list of all coauthors. The full list of authors has now been added and the Authors' contributions and competing interests section modified accordingly.The authors declare that they have no competing interests.ZZ prepared samples, performed western blot experiments and statistic analysis of the data as well as wrote manuscript. HN involved in analyzing the results and the statistical analysis, and revised the manuscript; PH participated in acquisition of data and performed immunohistochemistry and immunocytochemistry experiments. ZZ, HN and PH did trouble shooting to ensure experimental results reliable. GC helped revising the manuscript. TB and LS involved in collection of tissue used in this study; CA, HS and JC helped clarifying patients' clinical information. WX and YS designed experiments. YS supervised HN and PH in experiments and participated in preparation of the manuscript. All authors read and approved the final manuscript.
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