Search

Your search keyword '"Kish, Stephen J"' showing total 773 results
Start Over Author "Kish, Stephen J"
773 results on '"Kish, Stephen J"'

153. Brain α-synuclein accumulation in multiple system atrophy, Parkinson's disease and progressive supranuclear palsy: a comparative investigation

Author

Tong, Junchao, primary, Wong, Henry, additional, Guttman, Mark, additional, Ang, Lee C., additional, Forno, Lysia S., additional, Shimadzu, Mitsunobu, additional, Rajput, Ali H., additional, Muenter, Manfred D., additional, Kish, Stephen J., additional, Hornykiewicz, Oleh, additional, and Furukawa, Yoshiaki, additional

Published
2009
Full Text
View/download PDF

155. Brain serotonin transporter in human methamphetamine users

Author

Kish, Stephen J., primary, Fitzmaurice, Paul S., additional, Boileau, Isabelle, additional, Schmunk, Gregory A., additional, Ang, Lee-Cyn, additional, Furukawa, Yoshiaki, additional, Chang, Li-Jan, additional, Wickham, Dennis J., additional, Sherwin, Allan, additional, and Tong, Junchao, additional

Published
2008
Full Text
View/download PDF

157. Monoamine Oxidase-A Occupancy by Moclobemide and Phenelzine: Implications for the Development of Monoamine Oxidase Inhibitors.

Author

Chiuccariello, Lina, Cooke, Robert G., Miler, Laura, Levitan, Robert D., Baker, Glen B., Kish, Stephen J., Kolla, Nathan J., Rusjan, Pablo M., Houle, Sylvain, Wilson, Alan A., and Meyer, Jeffrey H.

Subjects
MONOAMINE oxidase, MOCLOBEMIDE, PHENELZINE (Drug), MONOAMINE oxidase inhibitors, PARKINSON'S disease
Abstract

Background: Monoamine oxidase inhibitors (MAOIs) are being developed for major depressive disorder, Alzheimer's, and Parkinson's Disease. Newer MAOIs have minimal sensitivity to tyramine, but a key limitation for optimizing their development is that standards for in vivo monoamine oxidase-A (MAO-A) occupancy in humans are not well established. The objectives were to determine the dose-occupancy relationship of moclobemide and the occupancy of phenelzine at typical clinical dosing. Methods: Major depressive episode (MDE) subjects underwent [11C]harmine positron emission tomography scanning prior to and following 6 weeks of treatment with moclobemide or phenelzine. Results: Mean brain MAO-A occupancies were 74.23 ± 8.32% for moclobemide at 300-600 mg daily (n = 11), 83.75 ± 5.52% for moclobemide at 900-1200 mg daily (n = 9), and 86.82 ± 6.89% for phenelzine at 45-60 mg daily (n = 4). The regional doseoccupancy relationship of moclobemide fit a hyperbolic function [F(x) = a(x/[b + x]); F(1,18) = 5.57 to 13.32, p = 0.002 to 0.03, mean 'a': 88.62 ± 2.38%, mean 'b': 69.88 ± 4.36 mg]. Multivariate analyses of variance showed significantly greater occupancy of phenelzine (45-60 mg) and higher-dose moclobemide (900-1200 mg) compared to lower-dose moclobemide [300-600 mg; F(7,16) = 3.94, p = 0.01]. Conclusions: These findings suggest that for first-line MDE treatment, daily moclobemide doses of 300-600 mg correspond to a MAO-A occupancy of 74%, whereas for treatment-resistant MDE, either phenelzine or higher doses of moclobemide correspond to a MAO-A occupancy of at least 84%. Therefore, novel MAO inhibitor development should aim for similar thresholds. The findings provide a rationale in treatment algorithm design to raise moclobemide doses to inhibit more MAO-A sites, but suggest switching from high-dose moclobemide to phenelzine is best justified by binding to additional targets. [ABSTRACT FROM AUTHOR]

Published
2016
Full Text
View/download PDF

158. Blocking of fatty acid amide hydrolase activity with PF-04457845 in human brain: a positron emission tomography study with the novel radioligand [11C]CURB.

Author

Boileau, Isabelle, Rusjan, Pablo M, Williams, Belinda, Mansouri, Esmaeil, Mizrahi, Romina, De Luca, Vincenzo, Johnson, Douglas S, Wilson, Alan A, Houle, Sylvain, Kish, Stephen J, and Tong, Junchao

Subjects
FATTY acid synthases, POSITRON emission tomography, RADIOLIGAND assay, HYDROLASES, ENZYMES
Abstract

Positron emission tomography with [11C]CURB was recently developed to quantify fatty acid amide hydrolase (FAAH), the enzyme responsible for hydrolyzing the endocannabinoid anandamide. This study investigated the test-retest reliability of [11C]CURB as well as its in vivo specificity and the validity of the kinetic model by using the highly specific FAAH inhibitor, PF-04457845. Five healthy volunteers completed test-retest [11C]CURB scans 1 to 2 months apart and six subjects completed baseline and blocking scans on the same day after PF-04457845 (p.o.) administration (1, 4, or 20 mg; n=2 each). The composite parameter λk3 (an index of FAAH activity, λ=K1/k2) was estimated using an irreversible two-tissue compartment model with plasma input function. There were no clinically observable responses to oral PF-04457845 or [11C]CURB injection. Oral administration of PF-04457845 reduced [11C]CURB binding to a homogeneous level at all three doses, with λk3 values decreased by ⩾91%. Excellent reproducibility and good reliability (test-retest variability=9%; intraclass correlation coefficient=0.79) were observed across all regions of interest investigated. Our findings suggest that λk3/[11C]CURB is a reliable, highly sensitive, and selective tool to measure FAAH activity in human brain in vivo. Moreover, PF-04457845 is a highly potent FAAH inhibitor (>95% inhibition at 1 mg) in living human brain. [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

159. [11C]-(+)-PHNO PET imaging of dopamine D2/3 receptors in Parkinson's disease with impulse control disorders.

Author

Payer, Doris E., Guttman, Mark, Kish, Stephen J., Tong, Junchao, Strafella, Antonio, Zack, Martin, Adams, John R., Rusjan, Pablo, Houle, Sylvain, Furukawa, Yoshiaki, Wilson, Alan A., and Boileau, Isabelle

Abstract

Dopamine agonist medications with high affinity for the D3 dopamine receptor are commonly used to treat Parkinson's disease, and have been associated with pathological behaviors categorized under the umbrella of impulse control disorders (ICD). The aim of this study was to investigate whether ICD in Parkinson's patients are associated with greater D3 dopamine receptor availability. We used positron emission tomography (PET) radioligand imaging with the D3 dopamine receptor preferring agonist [11C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) in Parkinson's patients with (n = 11) and without (n = 21) ICD, and age-, sex-, and education-matched healthy control subjects (n = 18). Contrary to hypotheses, [11C]-(+)-PHNO binding in D3-rich brain areas was not elevated in Parkinson's patients with ICD compared with those without; instead, [11C]-(+)-PHNO binding in ventral striatum was 20% lower ( P = 0.011), correlating with two measures of ICD severity ( r = −0.8 and −0.9), which may reflect higher dopamine tone in ventral striatum. In dorsal striatum, where [11C]-(+)-PHNO binding is associated with D2 receptor levels, [11C]-(+)-PHNO binding was elevated across patients compared with controls. We conclude that although D3 dopamine receptors have been linked to the occurrence of ICD in Parkinson's patients. Our findings do not support the hypothesis that D3 receptor levels are elevated in Parkinson's patients with ICD. We also did not find ICD-related abnormalities in D2 receptor levels. Our findings argue against the possibility that differences in D2/3 receptor levels can account for the development of ICD in PD; however, we cannot rule out that differences in dopamine levels (particularly in ventral striatum) may be involved. © 2015 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

161. Brain antioxidant systems in human methamphetamine users

Author

Moszczynska, Anna, primary, Fitzmaurice, Paul, additional, Ang, Lee, additional, Kalasinsky, Kathryn S., additional, Peretti, Frank J., additional, Aiken, Sally S., additional, Wickham, Dennis J., additional, Sherwin, Allan, additional, Nobrega, José N., additional, Forman, Henry J., additional, and Kish, Stephen J., additional

Published
2004
Full Text
View/download PDF

179. Dopa-Responsive Dystonia.

Author

Tarsy, Daniel, Frucht, Steven J., Fahn, Stanley, Furukawa, Yoshiaki, Guttman, Mark, and Kish, Stephen J.

Abstract

Patient 1: A 6-year-old girl with gait disturbance was introduced by an orthopedist in 1990, before the discovery of causative genes in dopa-responsive dystonia (DRD). Although early motor development was normal, she had Trendelenburg's symptoms resulting from a congenital dislocation of the left hip (acetabular dysplasia). In addition, she developed flexion-inversion of the left foot at the age of 3 years, which became aggravated toward the evening and was alleviated in the morning after sleep. Her postural dystonia spread to other limbs within 3 years but was more pronounced in the legs. Neurological examination also revealed symmetric hyperreflexia without extensor plantar responses, and rigid hypertonicity in the legs. Investigations, including copper metabolism and brain magnetic resonance imaging, were normal. Therapeutic trials with levodopa and tetrahydrobiopterin (BH4; the cofactor for tyrosine hydroxylase) were considered, and a lumbar puncture was performed to measure cerebrospinal fluid (CSF) pterins. She remarkably responded to low doses of levodopa but not to acute BH4 administration. After increasing the dosage of levodopa (20 mg/kg/day, without a decarboxylase inhibitor [DCI]) and undergoing an operation (acetabuloplasty) for the complicated condition, she became completely normal and was diagnosed as DRD. The diagnosis was supported by CSF data (decreased total biopterin and neopterin) and was confirmed later by genetic analysis (1,2). [ABSTRACT FROM AUTHOR]

Published
2005
Full Text
View/download PDF

182. Heightened Dopaminergic Response to Amphetamine at the D3Dopamine Receptor in Methamphetamine Users

Author

Boileau, Isabelle, Payer, Doris, Rusjan, Pablo M, Houle, Sylvain, Tong, Junchao, McCluskey, Tina, Wilson, Alan A, and Kish, Stephen J

Abstract

Neuroimaging studies in stimulant use (eg, cocaine, methamphetamine) disorders show that diminished dopamine release by dopamine-elevating drugs is a potential marker of relapse and suggest that increasing dopamine at the D2/3receptors may be therapeutically beneficial. In contrast, recent investigations indicate heightened D3receptor levels in stimulant users prompting the view that D3antagonism may help prevent relapse. Here we tested whether a ‘blunted’ response to amphetamine in methamphetamine (MA) users extends to D3-rich brain areas. Fourteen MA users and 15 healthy controls completed two positron emission tomographic scans with a D3-preferring probe [11C]-(+)-PHNO at baseline and after amphetamine (0.4 mg/kg). Relative to healthy controls, MA users had greater decreases in [11C]-(+)-PHNO binding (increased dopamine release) after amphetamine in D3-rich substantia nigra (36 vs 20%, p=0.03) and globus pallidus (30 vs 17%, p=0.06), which correlated with self-reported ‘drug wanting’. We did not observe a ‘blunted’ dopamine response to amphetamine in D2-rich striatum; however, drug use severity was negatively associated with amphetamine-induced striatal changes in [11C]-(+)-PHNO binding. Our study provides evidence that dopamine transmission in extrastriatal ‘D3-areas’ is not blunted but rather increased in MA users. Together with our previous finding of elevated D3receptor level in MA users, the current observation suggests that greater dopaminergic transmission at the D3dopamine receptor may contribute to motivation to use drugs and argues in favor of D3antagonism as a possible therapeutic tool to reduce craving and relapse in MA addiction.

Published
2016
Full Text
View/download PDF

183. Rapid Recovery of Vesicular Dopamine Levels in Methamphetamine Users in Early Abstinence

Author

Boileau, Isabelle, McCluskey, Tina, Tong, Junchao, Furukawa, Yoshiaki, Houle, Sylvain, and Kish, Stephen J

Abstract

We previously reported very low levels of dopamine in post-mortem striatum of chronic methamphetamine users, raising the possibility that restoration of normal dopamine levels could help in this addiction and perhaps prevent early relapse. To establish relevance of this finding to the living brain, we tested whether striatal [11C]-(+)-dihydrotetrabenazine binding, a vesicular monoamine transporter probe sensitive to changes in (stored) vesicular dopamine, is elevated in methamphetamine users. Chronic methamphetamine users underwent [11C]-(+)-dihydrotetrabenazine positron emission tomography scans during early (mean 2.6 days) and later (~10 days) abstinence. Striatal [11C]-(+)-dihydrotetrabenazine binding was elevated (suggesting low stored dopamine) in methamphetamine users (n=28; 2.6 days after last use) relative to controls (n=22) (+28%, p<0.0001) and correlated with severity and recency of drug use and with cognitive impairment and withdrawal symptoms. Mean [11C]-(+)-dihydrotetrabenazine binding levels in the subgroup of methamphetamine users who could remain abstinent ~10 days following last use (n=17) were normal at the follow-up scan. Our imaging data support post-mortem findings and suggest that chronic methamphetamine users have low brain levels of stored dopamine during very early abstinence from MA, which could contribute to behavioral and cognitive deficits. Findings also suggest a rapid recovery of stored dopamine in some methamphetamine users who become abstinent and who therefore might not benefit from dopamine replacement medication (eg, levodopa). Further study is necessary to establish whether those users who could not maintain abstinence for the second scan might have a more severe and persistent dopamine deficiency and who could benefit from this medication.

Published
2016
Full Text
View/download PDF

189. Elevated Monoamine Oxidase A Binding During Major Depressive Episodes Is Associated with Greater Severity and Reversed Neurovegetative Symptoms.

Author

Chiuccariello, Lina, Houle, Sylvain, Miler, Laura, Cooke, Robert G, Rusjan, Pablo M, Rajkowska, Grazyna, Levitan, Robert D, Kish, Stephen J, Kolla, Nathan J, Ou, Xiaoming, Wilson, Alan A, and Meyer, Jeffrey H

Subjects
THERAPEUTICS, MENTAL depression, MONOAMINE oxidase, HYPERSOMNIA, WEIGHT gain, POSITRON emission tomography, ANALYSIS of variance
Abstract

Inadequate treatment response occurs in approximately 40% of major depressive episodes (MDEs), and one approach to solve this is careful matching of treatment to the specific pathologies of MDE. One such biological abnormality is elevated monoamine oxidase A (MAO-A) levels, which occurs in the prefrontal and anterior cingulate cortex (PFC and ACC) during MDE; however, the subtypes for which this abnormality is most prominent are unknown. We hypothesized that MAO-A levels in the PFC and ACC are most elevated in MDE with greater severity and reversed neurovegetative symptoms (hypersomnia and either hyperphagia or weight gain). MAO-A VT (an index of MAO-A density) was measured using [11C]harmine positron emission tomography (PET) in 42 subjects with MDEs secondary to major depressive disorder and 37 healthy controls. The effect of severity and reversed neurovegetative symptoms on MAO-A VT in the PFC and ACC was analyzed using a multivariate analysis of variance (MANOVA). Greater severity and reversed neurovegetative symptoms were associated with elevated MAO-A VT in the PFC and ACC (MANOVA, severity: F(2,38)=5.44, p=0.008; reversed neurovegetative symptoms: F(2,38)=5.13, p=0.01). Increased MAO-A level, when greater severity and reversed neurovegetative symptoms are present, may explain the association of these clinical features with a preferential response to MAO inhibitors, which is especially well-evidenced for reversed neurovegetative symptoms in MDE. As MAO-A creates oxidative stress, facilitates apoptosis, and metabolizes monoamines, therapeutics opposing these processes are predicted to best treat MDE with greater severity and reversed neurovegetative symptoms. [ABSTRACT FROM AUTHOR]

Published
2014
Full Text
View/download PDF

197. Hereditary form of parkinsonism—dementia

Author

Muenter, Manfred D., primary, Forno, Lysia S., additional, Hornykiewicz, Oleh, additional, Kish, Stephen J., additional, Maraganore, Demetrius M., additional, Caselli, Richard J., additional, Okazaki, Haruo, additional, Howard, Frank M., additional, Snow, Barry J., additional, and Calne, Donald B., additional

Published
1998
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results