A5004921494- Muscle Physiology and Disorders
- Tuberous Sclerosis Complex Research
- Ion channel regulation and function
- Adipose Tissue and Metabolism
- Cardiac electrophysiology and arrhythmias
- Polyomavirus and related diseases
- Histiocytic Disorders and Treatments
- Cardiomyopathy and Myosin Studies
- Neurogenetic and Muscular Disorders Research
- Neuroscience and Neural Engineering
- Epilepsy research and treatment
- Eicosanoids and Hypertension Pharmacology
- Genetics and Neurodevelopmental Disorders
- Exercise and Physiological Responses
- Pharmacogenetics and Drug Metabolism
- Computational Drug Discovery Methods
- Biotin and Related Studies
- Pharmacological Effects and Toxicity Studies
- Nicotinic Acetylcholine Receptors Study
- Neurobiology and Insect Physiology Research
- Alcohol Consumption and Health Effects
- Tumors and Oncological Cases
- Genetic Neurodegenerative Diseases
- Gene expression and cancer classification
- Cystic Fibrosis Research Advances
TSC Alliance
2021-2024
Nobel Foundation
2022
Digital Research Alliance of Canada
2020
Pfizer (United States)
2004-2011
CNS Research (United States)
2003-2004
Howard Hughes Medical Institute
1993-1997
University of Colorado Anschutz Medical Campus
1997
Cleveland Clinic
1997
University of Iowa
1993-1996
Uppsala University
1995
BackgroundTuberous sclerosis complex is highly variable in clinical presentation and findings. Disease manifestations continue to develop over the lifetime of an affected individual. Accurate diagnosis fundamental implementation appropriate medical surveillance treatment. Although significant advances have been made past 15 years understanding treatment tuberous complex, current diagnostic criteria not critically evaluated or updated since last consensus conference 1998.MethodsThe 2012...
Tuberous sclerosis complex is a genetic disorder affecting every organ system, but disease manifestations vary significantly among affected individuals. The diverse and varied presentations progression can be life-threatening with significant impact on cost quality of life. Current surveillance management practices are highly variable region country, reflective the fact that last consensus recommendations occurred in 1998 an updated, comprehensive standard lacking incorporates latest...
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by accumulation of amyloid plaques and neurofibrillary tangles in the brain. The major components plaque, beta-amyloid peptides (Abetas), are produced from precursor protein (APP) activity beta- gamma-secretases. beta-secretase cleaves APP to define N-terminus Abeta1-x and, therefore, has been long- sought therapeutic target for treatment AD. gene encoding beta-site cleaving enzyme (BACE) was identified recently. However,...
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance management of manifestations. Advances knowledge approvals new therapies necessitated a revision those recommendations.Chairs working group cochairs from the 2012 International TSC Consensus Group were invited to meet...
Five distinct K+ channel cDNA molecules (RK1 to RK5) were cloned from either rat heart or aorta libraries. Four of the channels, RK1 RK4, are similar identical Shaker-like channels previously identified in brain Major differences among RK4 exist amino- and carboxyl-terminal regions amino acids representing potential extracellular sequence between S1 S2 hydrophobic domains. RK5 encodes a unique 490 having six domains but only five basic residues putative voltage-sensing domain. Unlike is...
The interaction of quinidine with a cloned human cardiac potassium channel (HK2) expressed in stable mouse L cell line was studied using the whole-cell tight-seal voltage-clamp technique. Quinidine (20 microM) did not affect initial sigmoidal activation time course current. However, it reduced peak current and induced subsequent decline, constant 8.2 +/- 0.8 msec, to 28 6% control (at +60 mV). concentration dependence HK2 block at mV yielded an apparent KD 6 microM Hill coefficient 0.9....
The dystroglycan complex is a transmembrane linkage between the cytoskeleton and basement membrane in muscle. One of components complex, alpha-dystroglycan binds both laminin muscle (laminin-2) agrin membranes. Dystroglycan has been detected nonmuscle tissues as well, but physiological role remained unknown. Here we show that during mouse development expressed epithelium. In situ hybridization revealed strong expression mRNA all studied epithelial sheets, not endothelium or mesenchyme....
Recent evidence suggests that succinate, long known as an intermediate in the citric acid cycle, may also have a role signaling molecule through GPR91 and activation of this receptor results blood pressure (BP) elevation via renin-angiotensin system. We sought to test hypothesis contributes BP hypertension. In addition we investigated whether elevated succinate diabetes could contribute increased rate gluconeogenesis condition.Circulating concentration was measured using liquid...
To gain insight into the molecular basis of cardiac repolarization, we have expressed K+ channels cloned from ventricular myocardium in Xenopus oocytes. A recently identified human channel isoform (human Kv1.4) has properties similar to 4-aminopyridine-sensitive calcium-insensitive component transient outward current. However, these recovered inactivation much slower than native channels. Hybrid consisting subunits different clones (delayed rectifier [Kv1.1, Kv1.2, and Kv1.5] were created by...
The 50-kDa dystrophin-associated glycoprotein (50-DAG) is a component of the dystrophin-glycoprotein complex, which links muscle cytoskeleton to extracellular matrix. 50-DAG specifically deficient in skeletal patients with severe childhood autosomal recessive muscular dystrophy and cardiac muscles BIO 14.6 cardiomyopathic hamsters. lack leads disruption dysfunction complex these diseases. cDNA encoding has now been cloned from rabbit muscle. deduced amino acid sequence predicts novel protein...
Cardiomyopathies are a diverse group of primary cardiac diseases, most which have poorly understood etiology. One type hereditary cardiomyopathy is caused by defects in the dystrophin gene Duchenne and Becker muscular dystrophy patients. Our laboratory has identified complex dystrophin-associated proteins skeletal muscle span sarcolemma, linking subsarcolemmal cytoskeleton to extracellular matrix. The absence patients leads loss both muscle, suggesting that one or more might lead other forms...
Mutations of copper,zinc-superoxide dismutase (cu,zn SOD) are found in patients with a familial form amyotrophic lateral sclerosis. When expressed transgenic mice, mutant human cu,zn SOD causes progressive loss motor neurons consequent paralysis and death. Expression profiling gene expression SOD1-G93A mouse spinal cords indicates extensive glial activation coincident the onset at 3 months age. This is followed by genes involved metal ion regulation (metallothionein-I, metallothionein-III,...
Journal Article Highly degenerate, inosine-containing primers specifically amplify rare cDNA using the polymerase chain reaction Get access Karen Knoth, Knoth 2Department of Pharmacology, Vanderbilt Medical SchoolNashville, TN, 37232, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Steven Roberds, Roberds Celeste Poteet, Poteet 1Department Molecular Physiology and Biophysics, Michael Tamkun USA2Department Nucleic Acids Research, Volume 16, Issue 22, 25...
Recombinant acetylcholine receptors (AChRs) expressed on the surface of cultured fibroblasts become organized into discrete membrane domains when 43-kD postsynaptic protein (43k) is co-expressed in same cells (Froehner, S.C., C. W. Luetje, P. B. Scotland, and J. Patrick, 1990. Neuron. 5:403-410; Phillips, D., M. Kopta, Blount, D. Gardner, H. Steinbach, Merlie. 1991. Science (Wash. DC). 251:568-570). Here we show that AChRs present fibroblast cell prior to transfection 43k are recruited...
Structure-based virtual screening was applied to design combinatorial libraries discover novel and potent soluble epoxide hydrolase (sEH) inhibitors. X-ray crystal structures revealed unique interactions for a benzoxazole template in addition the conserved hydrogen bonds with catalytic machinery of sEH. By exploitation favorable binding elements, two iterations library based on amide coupling were employed, guided principally by docking results enumerated products. Biological demonstrated as...
Autosomal recessive limb-girdle muscular dystrophies (AR LGMD) represent a heterogeneous group of diseases with wide spectrum clinical variability, classified phenotypically into two main groups, the most severe forms (Duchenne-like dystrophy, DLMD, or childhood autosomal SCARMD) and milder forms. Four genes causing AR LGMD have been mapped: 15q (LGMD2a), 2p (LGMD2b), 13q locus (LGMD2c) adhalin gene on chromosome 17q (LGMD2d). In present report we performed linkage analysis markers in three...