Timothy Counihan

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N-methyl-D-aspartate receptors (NRs) play an important role in basal ganglia function. By using in situ hybridization with ribonucleotide probes, we investigated the regional and cellular distribution of NR subunit mRNA expression in the human basal ganglia: caudate nucleus, putamen, lateral globus pallidus (LGP), and medial globus pallidus (MGP). Analysis(More)
N-methyl-D-aspartate receptor (NR) activation in the hippocampus and neocortex plays a central role in memory and cognitive function. We analyzed the cellular expression of the five NR subunit (NR1 and NR2A-D) mRNAs in these regions with in situ hybridization and human ribonucleotide probes. Film autoradiograms demonstrated a distinct pattern of(More)
Topoisomerase II (TOP2) removes torsional stress from DNA and facilitates gene transcription by introducing transient DNA double-strand breaks (DSBs). Such DSBs are normally rejoined by TOP2 but on occasion can become abortive and remain unsealed. Here we identify homozygous mutations in the TDP2 gene encoding tyrosyl DNA phosphodiesterase-2, an enzyme that(More)
IMPORTANCE Mutations in the gene encoding parkin (PARK2) are the most common cause of autosomal recessive juvenile-onset and young-onset parkinsonism. The few available detailed neuropathologic reports suggest that homozygous and compound heterozygous parkin mutations are characterized by severe substantia nigra pars compacta neuronal loss. OBJECTIVE To(More)
Evidence is accumulating that glutamate-mediated excitotoxicity plays an important role in neuronal degeneration in Parkinson's disease (PD). In addition, alterations in excitatory amino acid neurotransmission in the basal ganglia contribute to the clinical manifestations of motor dysfunction. However, detailed knowledge of the anatomical distribution and(More)
Freezing of gait (FOG) is a common motor symptom of Parkinson’s disease (PD), which presents itself as an inability to initiate or continue gait. This paper presents a method to monitor FOG episodes based only on acceleration measurements obtained from a waist-worn device. Three approximations of this method are tested. Initially, FOG is directly detected(More)
BACKGROUND After several years of treatment, patients with Parkinson's disease (PD) tend to have, as a side effect of the medication, dyskinesias. Close monitoring may benefit patients by enabling doctors to tailor a personalised medication regimen. Moreover, dyskinesia monitoring can help neurologists make more informed decisions in patient's care. (More)
BACKGROUND Calreticulin (CRT) is a chaperone protein, which aids correct folding of glycosylated proteins in the endoplasmic reticulum (ER). Under conditions of ER stress, CRT is upregulated and may be displayed on the surface of cells or be secreted. This 'ecto-CRT' may activate the innate immune response or it may aid clearance of apoptotic cells. Our and(More)
Limbic encephalitis (LE), which is typically characterized by acute or subacute cognitive disturbance with memory impairment, seizures, behavioral changes, and bilateral medial temporal hyper-intensity on MRI [1], may be infectious or non-infectious (immune-mediated). Immune-mediated LE while most commonly paraneoplastic [2], may be non-paraneoplastic(More)
Perineuritis is an unusual cause of direct peripheral nerve injury. We describe the clinicopathologic features of a 56-year-old man with mononeuritis multiplex due to Lyme disease; sural nerve biopsy demonstrated florid perineuritis. Treatment with intravenous ceftriaxone resulted in marked neurologic improvement. This study supports the notion that(More)