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Biomedical subjects

T N Chase

Publications and source records attributed to T N Chase.

At least 145 records · Page 8Linked to original sources
PubMed1992

CSF galanin and neuropeptide Y immunoreactivity in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) has been associated with degenerative changes in cholinergic and dopaminergic neurons in several brain regions. Since acetylcholine is colocalized with the neuropeptide galanin in certain neuronal populations, we measured the concentration of this neuropeptide and neuropeptide Y in cerebrospinal fluid (CSF) of 11 patients with PSP and in 16 age-matched healthy controls. No significant alterations in the CSF levels of galanin or neuropeptide Y were found.

Aged↗
PubMed1992

Heterogeneity in Alzheimer's disease: progression rate segregated by distinct neuropsychological and cerebral metabolic profiles.

In an attempt to define possible subgroups of Alzheimer's disease, 21 patients satisfying current clinical diagnostic criteria for this disorder were divided on the basis of progression rates of symptoms. Thirteen patients with relatively rapid intellectual deterioration did not differ from eight patients showing slow progression with respect to global intellectual performance, sex, or age at onset of symptoms. Neuropsychological testing revealed that although the two groups were indistinguishable in verbal or visuospatial functions associated with the parietotemporal cortex, the more rapidly deteriorating group had significantly greater impairment in executive functions attributed to the frontal lobe. PET scans showed equivalent reductions in glucose metabolism in the parietotemporal cortex, but patients with relatively fast progression had significantly greater hypometabolism frontally. These results suggest an association between relatively severe frontal lobe involvement and a rapid clinical course that might have important implications for the development of treatment strategies for patients with Alzheimer's disease.

Aged↗
PubMed1992

Failure of buspirone and verapamil to improve spasmodic torticollis.

The effects of buspirone and verapamil on spasmodic torticollis were investigated in two double-blind, placebo-controlled crossover studies. Buspirone was given in doses of 20-100 mg/day for 4 weeks to 14 patients; verapamil was given in doses of 40-100 mg/day for 3 weeks to 8 patients. Neither drug improved symptoms of the movement disorder (posture, motility, rigidity, tremor), pain, perceived stress, or mood, either in the whole group or in any individual patient.

Adult↗
PubMed1992

A comparison of FDG PET and IQNB SPECT in normal subjects and in patients with dementia.

Prior studies of patients with dementia have found similar qualitative patterns of cerebral glucose utilization with [18F]2-fluoro-2-deoxyglucose (FDG) PET and of putative muscarinic receptor activity with [123I]3-quinuclidinyl-4-iodobenzilate (IQNB). This raised doubts about whether receptor binding determines IQNB distribution and whether clinical information in IQNB scans is unique. To compare the methods directly, 4 normal volunteers and 7 patients with dementia underwent FDG PET and high-resolution IQNB SPECT scans. In normal subjects, relative regional activity from the paired scans was only weakly correlated (r = 0.29). Some regions (e.g., thalamus, frontal cortex) showed a clear disassociation of activity. In demented patients, IQNB scans tended to show larger defects than FDG scans, although one focal defect appeared only with PET. Results suggest that IQNB SPECT data are not primarily related to general physiological activity or regional cerebral blood flow and are not explained by attenuation or volume-averaging artifacts. Further studies should investigate whether IQNB scanning is a more sensitive in vivo measure of the extent of Alzheimer's disease than is FDG PET.

Adult↗
PubMed1992

Deprenyl effects on levodopa pharmacodynamics, mood, and free radical scavenging.

Clinical evidence suggests that deprenyl may slow progression of Parkinson's disease, although mechanisms underlying this putative neuroprotective action remain poorly understood. To address this issue, we studied deprenyl in 12 parkinsonian patients using a single-blind, placebo-controlled, crossover design. After 1 month, deprenyl (10 mg/d) decreased the optimal levodopa requirement by 24% (oral) and 16% (intravenous). Levodopa-induced dyskinesias were prolonged by 430%, and antiparkinsonian action by 44%. Mood improved by 47%. One month after withdrawing deprenyl, effects on dyskinesias and mood had yet to return to baseline. There was no change in activities of circulating glutathione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase, and catalase, nor in levels of lipid peroxide and vitamin E. Deprenyl also failed to modify CSF levels of total glutathione and activities of glutathione peroxidase or superoxide dismutase. These effects on levodopa pharmacodynamics and mood complicate the interpretation of available investigations of deprenyl's neuroprotective action and increase the risk of adverse effects of levodopa.

Affect↗
PubMed1992

Partial dopamine agonist therapy of levodopa-induced dyskinesias.

We administered the partial dopamine agonist terguride under controlled conditions to patients with Parkinson's disease (PD), both as monotherapy and in conjunction with intravenous levodopa. Terguride produced a dose-dependent decrease in levodopa-induced dyskinesias (up to 53%) in seven patients without concomitant worsening of parkinsonism, and had no significant antiparkinsonian effect when administered alone. Partial dopamine agonists may hold some promise in the adjuvant therapy of patients with advanced PD.

Adult↗
PubMed1992

Neuropsychological and glucose metabolic profiles in asymmetric Parkinson's disease.

Patients with predominantly unilateral parkinsonian signs may provide a unique opportunity to evaluate the cerebral representation of cognitive functions characteristically affected in idiopathic Parkinson's disease. Twenty hemiparkinsonian patients (ten left and ten right) and 10 healthy controls, matched for age and education, were studied with neuropsychological tests and positron emission tomography. Both right and left hemiparkinsonians evidenced impairments in visuospatial and verbal episodic memory function, but had no deficits in executive abilities, compared to controls. None of the neuropsychological test scores distinguished right from left hemiparkinsonians. Glucose metabolic profiles were identical for the three groups in all cortical areas assessed; in the subcortex however, lenticular hypermetabolism contralateral to the predominant side of motor involvement was evident in the left hemiparkinsonian group. Correlational analysis revealed that higher glucose metabolic rates in the basal ganglia of these hemiparkinsonians were associated with lower visuospatial test scores. In frontal and parietal cortex, decreasing glucose metabolism was positively associated with neurobehavioral function; in temporal cortex, measures of attention and memory decreased with increasing glucose metabolic rates.

Adult↗
PubMed1991

Regional cerebral glucose metabolism compared in rodents and humans.

In order to compare regional brain glucose metabolism in rats and humans, this parameter was measured using Sokoloff's deoxyglucose method in rats, and positron emission tomography with magnetic resonance imaging in humans. An atlas of cerebral regions of interest common to both species was developed to facilitate the evaluation of the relationship in regional values. We found among the regions studied a significant positive correlation in their metabolic values (r = 0.72, P less than 0.001) and coefficients of variation (r = 0.59, P less than 0.01) suggesting that regional brain glucose consumption is comparable between rat and human. Results of this study support the view that rat and human brain may be phylogenetically linked functionally as well as anatomically.

Aged↗
PubMed1991

The limbic-hypothalamic-pituitary-adrenal axis in Huntington's disease.

The functional integrity of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis was studied in 10 patients with Huntington's disease (HD) and 10 age- and weight-matched control subjects by measuring basal ACTH and cortisol secretion, analyzing the subjects' ACTH and cortisol responses to corticotropin-releasing hormone (CRH) challenge, and by means of the dexamethasone-suppression test (DST). Basal cortisol and ACTH levels were significantly higher in patients with HD compared with controls. Following CRH administration, ACTH responses tended to be blunted in concert with normal cortisol levels. Two patients with HD and one control subject were DST nonsuppressors. Post-DST plasma dexamethasone levels were 57% lower among patients compared with the control group. Only in the HD group age was there an important variable in influencing spontaneous cortisol secretion as well as plasma dexamethasone levels during DST. These results suggest that patients with HD have an endogenous CRH overdrive, possibly due to a loss of (GABA) gamma-aminobutyric acid-containing neurons, and that age might have an effect on the outcome of LHPA axis function tests in patients only.

Adrenocorticotropic Hormone↗
PubMed1991

Opioid peptides in Parkinson's disease: effects of dopamine repletion.

Neurotransmitters other than dopamine, including neuropeptides, could have important pathophysiologic and therapeutic roles in Parkinson's disease. Both Met-enkephalin, the main transmitter of the striatopallidal pathway, and dynorphin, one of the co-transmitters of the striatonigral pathway display complex anatomic and biochemical interactions with the basal ganglionic dopamine system. In this study, the cerebrospinal fluid content of a proenkephalin derivative, Met5 enkephalin-Arg6-Gly7-Leu8 (MERGL), was found in significantly low concentrations in parkinsonian patients following overnight withdrawal of all medications compared with control subjects, and failed to change after at least 16 h of steady-state, optimal doses of levodopa infusion intravenously. MERGL levels increased with advancing age among normal individuals but not among patients with Parkinson's disease. In contrast dynorphin A(1-8) levels were not different between the two study groups, did not change with levodopa therapy, and failed to correlate with age or any indices of disease progression. These observations, consistent with post-mortem studies on Parkinson brains and contrary to findings in animal models of Parkinsonism, suggest that abnormality of the enkephalin system in this disease is due to involvement of these striatal neurons in the primary pathologic process.

Adult↗
PubMed1991

The kappa-opioid receptor agonist spiradoline differentially alters the rotational response to dopamine D1 and D2 agonists.

The effect of the selective kappa-opioid agonist, spiradoline, on rotational behavior induced by a dopamine D1 or D2 agonist was examined in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. Spiradoline reduced the rotational response to the D1 agonist SKF 38393 in a dose-dependent manner. Spiradoline had no effect on the total number of turns elicited by the D2 agonist quinpirole, but did alter the pattern of quinpirole-induced rotation at the highest dose tested. By itself, spiradoline did not have any obvious effects on motor behavior and did not cause rotation in either the ipsilateral or contralateral direction. These data suggest that kappa receptor stimulation, possibly mediated by the endogenous agonist dynorphin under physiological conditions, may function to dampen striatal output through the D1 receptor-regulated striatonigral pathway.

Analgesics↗
PubMed1991

Levodopa replacement therapy alters enzyme activities in striatum and neuropeptide content in striatal output regions of 6-hydroxydopamine lesioned rats.

The effects of striatal dopamine denervation and levodopa replacement therapy on neuronal populations in the rat striatum were assessed by measurement of glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) activities in the striatum, dynorphin and substance P concentrations in the substantia nigra, and enkephalin concentration in the globus pallidus. Rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway were treated for 21 days with levodopa (100 mg/kg/day, i.p., with 25 mg/kg benserazide) on either an intermittent (b.i.d.) or continuous (osmotic pump infusion) regimen and sacrificed following a three day drug washout. In saline-treated control rats, striatal GAD activity and globus pallidus enkephalin content were elevated and nigral substance P content was reduced ipsilateral to the 6-OHDA lesion. Intermittent levodopa treatment further increased GAD activity, decreased CAT activity, restored substance P to control levels, markedly increased dynorphin content, and had no effect on enkephalin. In contrast, continuous levodopa elevated globus pallidus enkephalin beyond the levels occurring with denervation, but had no effect on any of the other neurochemical measures. These results indicate that striatal neuronal populations are differentially affected by chronic levodopa therapy and by the continuous or intermittent nature of the treatment regimen. With the exception of substance P, levodopa did not reverse the effects of the 6-OHDA lesion but, rather, either exacerbated the lesion-induced changes (e.g. GAD and enkephalin) or altered neurochemical markers which had been unaffected by the lesion (e.g. CAT and dynorphin).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of Gi protein ADP-ribosylation induced by pertussis toxin on dopamine-mediated behaviors.

The effect of Gi protein modification produced by intrastriatal pertussis toxin injection on dopamine (DA)-mediated behaviors was studied. Administration of the selective D2 agonist quinpirole induced ipsilateral rotation but the selective D1 agonist SKF 38393 did not. However, SKF 38393 was able to increase the rotation induced by quinpirole. The selective D2 antagonist raclopride and the selective D1 antagonist SCH 23390 both blocked the effect of quinpirole. Striatal levels of cAMP were measured in both intact and pertussis toxin injected striatum. SKF 38393 induced a significant increase in cAMP, but quinpirole had no effect. When both drugs were administered together, quinpirole attenuated the SKF 38393-induced increase in cAMP levels. Moreover, quinpirole-induced attenuation of SKF 38393 effect was greater in intact striatum. In pertussis toxin-injected striatum, quinpirole only attenuated SKF 38393-induced increase of cAMP to control levels. This imbalance between intact and injected striatum might be the cause of the rotation in pertussis toxin-injected rats suggesting an important role for G proteins in DA receptor interactions.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Prolonged infusion of quinolinic acid into rat striatum as an excitotoxic model of neurodegenerative disease.

The neurotoxic effects of prolonged exposure of rat striatum to quinolinic acid in vivo was evaluated through assays of neurochemical markers for major neuronal populations. Continuous intrastriatal quinolinic acid infusion for 14 days produced a dose-dependent depletion of striatal choline acetyltransferase (ChAT) activity, glutamic acid decarboxylase (GAD) activity, and somatostatin content. ChAT activity was significantly reduced by quinolinic acid at doses of 90, 270, and 540 nmol/day, while GAD activity and somatostatin content were decreased only at doses of 270 and 540 nmol/day. NADPH-diaphorase histochemistry revealed a loss of striatal NADPH-diaphorase neurons as a result of quinolinic acid infusion at a dose of 270 nmol/day. The neurotoxic lesion induced by prolonged quinolinic acid exposure in vivo can be used as a potential model for studying excitotoxic mechanisms in neurodegenerative disease.

Animals↗
PubMed1991

Somatostatin replacement therapy for Alzheimer dementia.

Somatostatin is consistently diminished in brains of patients with Alzheimer's disease. To evaluate whether pharmacological restoration of this transmitter deficit has therapeutic value, the synthetic analogue octreotide was administered intravenously to 14 Alzheimer patients under double-blind, placebo-controlled conditions. At the highest dose administered, spinal fluid concentrations approximated those found in brains of experimental animals receiving behaviorally effective amounts of the drug. Neuropsychological testing, however, showed no clinically significant improvement. Coadministration of octreotide and physostigmine to 1 patient also failed to improve cognition. Positron emission tomographic studies in 6 patients revealed a generalized decrease in glucose metabolism as a result of octreotide infusion. These findings suggest that stimulation of the somatostatin system has no value in the symptomatic treatment of Alzheimer dementia.

Aged↗
PubMed1991

Visuospatial cognition in Huntington's disease.

The notion of specificity of visuospatial dysfunction in Huntington's disease (HD) was evaluated in a sample of afflicted patients as a function of symptom duration, age at onset, and overall dementia severity. Factor analytic procedures indicated that overall visuospatial processing capacity (factor 1) as well as the ability for spatial manipulation (factor 3) was markedly affected in HD patients. In contrast, consistency of spatial judgment (factor 2) appeared to remain relatively intact in these patients. Age at onset seemed to have no relationship with any of these variables, whereas dementia severity demonstrated a significant relationship with overall visuospatial processing capacity. Most importantly, duration of symptoms was significantly associated with the declining ability to mentally perform spatial manipulations. The observation of circumscribed visuospatial impairment in HD patients may have important consequences for the further understanding of the neurobehavioral consequences of this disorder.

Adult↗