PubMed Health⌕ Search

Biomedical subjects

S Gauthier

Publications and source records attributed to S Gauthier.

At least 19 recordsLinked to original sources
PubMed1992

Characterization and autoradiographic distribution of [3H]AF-DX 384 binding to putative muscarinic M2 receptors in the rat brain.

The novel radioligand [3H]AF-DX 384 binds specifically and saturably to putative muscarinic M2 receptor sites in homogenates of rat cerebral cortex. In saturation studies, [3H]AF-DX 384 appears to bind to two subpopulations of sites/states, one of high affinity (Kd1 = 0.28 +/- 0.08 nM) and another of low affinity (Kd2 = 28.0 +/- 5.0 nM). The maximal binding capacity (Bmax) of [3H]AF-DX 384 binding sites represented 9.7 +/- 2.3 fmol/mg protein (Bmax1) and 1993 +/- 551 fmol/mg protein (Bmax2) for the high and low affinity sites/states, respectively. The ligand selectivity profile of [3H]AF-DX 384 (at 2 nM) revealed that (-)-quinuclidinyl benzylate = atropine greater than 4-diphenylacetoxy-N-methylpiperidine methobromide greater than AQ-RA 741 greater than AF-DX 384 greater than UH-AH 371 much greater than methoctramine greater than oxotremorine-M greater than hexahydro-sila-defenidol much greater than pirenzepine greater than carbamylcholine much much greater than nicotine. This suggests that under our assay conditions [3H]AF-DX 384 binds mostly to M2-like muscarinic receptors in the rat central nervous system. This is further supported by the clear M2-like pattern of distribution observed using quantitative receptor autoradiography. High densities of specific labelling were seen in areas such as the hypoglossal nucleus, the pontine nucleus, the superior colliculus, the motor trigeminal nucleus, various thalamic nuclei and certain cortical laminae. Compared to [3H]AF-DX 116, the percentage of specific binding detected with [3H]AF-DX 384 was much higher. This is likely to be related to the greater chemical stability and affinity of [3H]AF-EX 384. In addition, autoradiograms obtained with [3H]AF-DX 384 (2 nM) are of better quality with film exposure periods five shorter than those needed for [3H]AF-DX 116 (10 nM). Therefore, [3H]AF-DX 384 displays a good selectivity for muscarinic M2 sites and offers major advantages, including higher affinity and greater stability, over previously used ligands.

Animals↗
PubMed1992

Spectral analysis of the rapid eye movement sleep electroencephalogram in right and left temporal regions: a biological marker of Alzheimer's disease.

Spectral analysis of electroencephalograms (EEGs) for both wakefulness and rapid eye movement (REM) sleep was performed over the temporal regions in 8 patients with mild to moderate Alzheimer's disease and in 8 age-matched control subjects. EEG slowing in Alzheimer patients was found to be much more prominent during REM sleep than during wakefulness. In addition, asymmetry on the awake EEG of Alzheimer patients was found to be even more prominent than on the REM sleep EEG. When EEG values of the most impaired hemisphere during REM sleep were examined, no overlap was found between the two groups either for the ratio of slow to fast frequencies or for percent power of each of the frequency bands. This was not the case for the awake EEG. These results suggest that diagnostically meaningful cutoff values for discriminating patients with mild to moderate Alzheimer's disease from age-matched control subjects can be derived from the REM sleep EEG of the temporal lobe.

Aged↗
PubMed1992

Antibody to beta-amyloid precursor protein recognizes an intermediate filament-associated protein in Alzheimer's and control fibroblasts.

The expression of beta-amyloid precursor protein (BAPP) and its mRNAs was studied in fibroblasts obtained from patients afflicted with Alzheimer's disease (AD) and age-matched controls. Using reverse transcriptase-polymerase chain reaction (RT-PCR), transcripts corresponding to 770, 751, 714, and 695 amino acids were detected in both AD and control fibroblasts. Antibody 22C11 against BAPP (Boehringer Mannheim) labeled an intracellular protein, specifically localized to the intermediate filament network. In addition to bands of the predicted molecular weights for BAPP (120-135 kDa), Western blotting revealed a 57 kDa band which was not evident in samples of human brain. As cytoskeletal elements are vital in maintaining cellular architecture and various cell interactions, localization of BAPP or a related molecule to the cytoskeleton suggests a possible structural role for this protein within the cell.

Alzheimer Disease↗
PubMed1992

Modulation of gamma-actin and alpha 1-tubulin expression by corticosterone during neuronal plasticity in the hippocampus.

Evidence is given for altered gene expression of gamma-actin in the hippocampus in response to entorhinal cortex lesion (ECL). Time course analysis reveals a progressive repression of gamma-actin expression between 4 and 14 days post-lesion, coinciding with the early and middle phases of the hippocampal reinnervation process. RNA prevalence returns to near control values at 30 days post-lesion. Corticosterone administration, which is known to impair the reinnervation process in ECL rats, prevents the lesion-induced reduction in gamma-actin expression and blocks the induction of alpha 1-tubulin in the deafferented hippocampus. The timing of response of gamma-actin to ECL and its modulation by glucocorticoid administration support suggestions that gamma-actin has an important role to play in neuronal cytoarchitecture remodelling during hippocampal reinnervation.

Actins↗
PubMed1992

The psychological and physical health of family members caring for an elderly person with dementia.

Most elderly persons with dementia are cared for at home, usually by the spouse or an adult child. The objective of the present study was to determine whether there is an excess of psychological and physical health problems among family caregivers (CGs) of elderly persons with dementia. Data were obtained by interview from close family members of dementia patients (CGs), and from a comparison group made up of close family members of patients undergoing cataract surgery (non-caregivers, NCGs). CGs had significantly higher levels of depression and physical symptoms than NCGs. The association between caregiving and the health variables was stronger among subjects who were the patient's spouse than among those who were the patient's child. Furthermore, greater behavioral disturbance in the demented patient was associated with higher levels of morbidity in the CG. The results suggest that CGs might benefit from careful monitoring of their health status, and from greater access to specialized support services.

Aged↗
PubMed1992

Comparative alterations of nicotinic and muscarinic binding sites in Alzheimer's and Parkinson's diseases.

We have recently reported on the differential alterations of various cholinergic markers in cortical and subcortical regions in Alzheimer's disease (AD). The main purpose of the present study was to determine if cholinergic deficits observed in patients with AD are unique to this disorder or can be generalized to others such as idiopathic Parkinson's disease (PD) and PD with Alzheimer-type dementia (PD/AD). Muscarinic M1, M2, and nicotinic receptor binding parameters (KD and Bmax) were determined in various cortical and subcortical areas using selective radioligands ([3H]pirenzepine, [3H]AF-DX 116, and N[3H]methylcarbamylcholine). Choline acetyltransferase activity was also determined as a marker of the integrity of cholinergic innervation. Alterations of cholinergic markers are comparable in cortical areas in AD, PD, and PD/AD brains. In frontal and temporal cortices, as well as in the hippocampus, choline acetyltransferase activity and binding capacities of M2 and nicotinic binding sites are similarly decreased in these three disorders compared with age-matched control values. M1 receptor binding parameters are not significantly modified in cortical areas in patients with these disorders. In contrast, important differences between AD and PD brain tissues are found in subcortical areas such as the striatum and the thalamus. The density of M1 sites is significantly increased in striatal areas only in patients with AD, whereas densities of nicotinic sites are decreased in thalamus and striatum in PD and PD/AD, but not AD, brain tissues. The binding capacity of M2 sites is apparently unchanged in subcortical areas in all three disorders, although tendencies toward reductions are observed in the striatum of PD and PD/AD patients. Thus, although comparable alterations of various cholinergic markers are observed in cortical areas in the three neurological disorders investigated in the present study, important differences are seen in subcortical areas. This may be relevant to the respective etiological and clinical profiles of AD and PD.

Aged↗
PubMed1992

The organization of stepping in patients with Parkinson's disease: bradykinesia or discoordination?

The purpose of this experiment was to quantify and analyse multijoint coordination of patients with Parkinson's disease (N = 5) and control subjects (N = 5) during forward and backward stepping motions executed at different cadences. Coordinates of reflective markers placed on the shoulder, hip, knee, ankle and metatarsal joints were recorded in the sagittal plane using a video motion analysis system. Kinematic and kinetic analyses provided angular displacements and velocities as well as joint moments of force and powers. Results suggest the presence of two types of discoordination: one type is velocity-dependent, hence related to bradykinesia, whereas the other type appears to reflect qualitatively different coordination patterns.

Aged↗
PubMed1992

Sustained release antiparkinson agents: controlled release levodopa.

The rationale for sustained release oral levodopa preparations is to deliver levodopa in the areas of maximal intestinal absorption in a slow and predictable way, leading to stable plasma levodopa levels and brain dopamine levels, therefore resulting in a lengthened duration of action. Sinemet CR is the prototype of such preparations, with demonstrated efficacy in decreasing periods of akinesia in parkinsonian patients with mild to moderate motor fluctuations. Total doses of levodopa are raised 10 to 30% because of the lowered bioavailability; diphasic dyskinesias may increase at the end of the day. Tolerance is good in de novo patients and studies are in progress to establish if early treatment with Sinemet CR delays the onset or attenuates the severity of motor fluctuations as compared to standard Sinemet.

Antiparkinson Agents↗
PubMed1991

Determination of bovine butterfat triacylglycerols by reversed-phase liquid chromatography and gas chromatography.

Triacylglycerols (TGs) from a sample of summer butterfat (bovine milk) were analysed and fractionated by reversed-phase liquid chromatography (RPLC). Fatty acid and TG composition of eac of the 47 RPLC fractions ranging from 0.1 to 6.9% were determined by capillary gas chromatography. The data were used together to determine the quantitative composition of the molecular species of TGs. A large number of TG species, accounting for 80% of the total, could be unequivocally identified and individually determined. The combination of the chromatographic methods used proved to be a powerful and accurate approach for the determination of molecular species of TGs in a complex fat, but also a difficult and time-consuming task.

Animals↗
PubMed1991

Environment, genetics and idiopathic Parkinson's disease.

Since Idiopathic Parkinson's disease (IPD) was first described more than 170 years ago, there have been major advances in the understanding of the etiology of the disease as well as in its treatment. This article will review current knowledge concerning the role of the environment, genetic hypotheses and the aging factor in the etiology of IPD and proposes a complex interaction involving all these factors. Hypotheses regarding mitochondrial inhibition and free radical generation in IPD are discussed in relation to the mechanism of action of neurotoxins known to produce parkinsonian syndromes.

Aging↗
PubMed1991

Modulation of locomotor patterns and spasticity with clonidine in spinal cord injured patients.

This double blind cross-over study, involving 9 chronic spinal cord injured (SCI) patients (6 paraplegic and 3 paretic), was a first attempt to investigate the effects of the noradrenergic agonist, clonidine, on the modulation of the locomotor pattern and spasticity in patients with spinal cord lesions. Electromyographic (EMG), footswitch and video recordings were made as the patients walked on a treadmill with the support of an overhead harness if needed. Overground locomotion was also assessed in the paretic patients. All 3 spastic paretic patients had kinematic deviations and abnormal EMG recruitment profiles during the premedication or placebo sessions. With clonidine therapy one patient demonstrated a marked improvement in locomotor function. This patient progressed from non-ambulation to limited independent ambulation as the extent of coactivation in antagonist muscles decreased. The other 2 paretics who presented limited spasticity showed minimal changes while on clonidine. In the paraplegic patients, clonidine did not elicit locomotor activity, although there were marked reductions in stretch reactions and clonus during assisted locomotion. They remained incapable of locomotion, either during the control period or during the clonidine therapy. These results indicate that clonidine may be a potentially useful medication for both locomotion and certain manifestations of spasticity in SCI patients but further investigation is warranted.

Adult↗
PubMed1991

Treatment of Alzheimer's disease: hopes and reality.

The relative failure of symptomatic therapeutic trials for Alzheimer's disease using non-selective cholinergic agonists brings about the need for longitudinal studies with parallel designs aimed at disease stabilization, using trophic substances or amyloid suppressors.

Alzheimer Disease↗
PubMed1991

Spatial disorientation in persons with early senile dementia of the Alzheimer type.

Although spatial disorientation is frequently observed in persons with Alzheimer disease, it is not well understood. A descriptive study was conducted to examine spatial skills associated with spatial orientation. Spatial tasks were selected and grouped into three types of spatial skills: perceptual, cognitive, and functional. These spatial tasks were administered to a group of 15 persons with senile dementia of the Alzheimer type (SDAT) (early Alzheimer disease) and a group of 15 control subjects. The results indicated that the subjects with SDAT were impaired on half of the perceptual spatial tasks and all of the cognitive spatial tasks. On the functional spatial tasks, however, the subjects with SDAT showed impaired skills in the new environment but intact skills in familiar environments. Spatial disorientation poses a danger and limits a person's ability to independently perform daily activities that require navigation outside of the home. Occupational therapy should therefore include the assessment of spatial orientation skills in persons who are in the early stages of dementia.

Activities of Daily Living↗
PubMed1990

Tetrahydroaminoacridine-lecithin combination treatment in patients with intermediate-stage Alzheimer's disease. Results of a Canadian double-blind, crossover, multicenter study.

We studied the efficacy and safety of oral tetrahydroaminoacridine (THA) combined with lecithin in 52 patients with Alzheimer's disease. The maximal tolerated dose of THA (up to 100 mg per day) was determined during an eight-week titration period, after which the tolerated dose of THA or placebo was given during two sequential randomized periods of treatment lasting eight weeks each. Highly purified lecithin (4.7 g per day) was administered during all phases of the study. Efficacy was expressed in terms of scores on the Mini-Mental State (MMS) test, the modified MMS test, the Hierarchic Dementia Scale, the Rapid Disability Rating Scale-II, and the behavioral scale of Reisberg et al. Safety was assessed by careful clinical monitoring as well as serial measurements of liver aminotransferases. Forty-six patients completed the titration period, and 39 completed the double-blind period, during which only the MMS score showed a small but significant increase (P less than 0.05) after four weeks of treatment with THA. Autonomic side effects of THA were common but mild. Reversible elevations of serum aspartate and alanine aminotransferase levels to three or more times the upper limit of normal occurred in 17 percent of patients; most of the patients affected were women. A liver biopsy performed in one patient showed resolving focal liver-cell necrosis. These studies fail to demonstrate a significant clinical benefit of THA given orally in a maximal dose of 100 mg per day over a period of eight weeks in combination with lecithin.

Administration, Oral↗
PubMed1990

Delayed visual feedback and movement control in Parkinson's disease.

The dependence of movement on visual information was compared for healthy individuals and Stage II-III patients with Parkinson's disease (PD). A time delay (0-1400 ms) was introduced into a visually guided motor tracking task which required the subject to maintain constant index finger position relative to a stationary baseline on an oscilloscope. For healthy individuals, delayed visual feedback induced complex oscillations in finger displacement. Similar results were obtained for four of eight patients with PD. However, oscillations were not induced in four of eight patients with PD because of reduced gain and/or a higher tremor amplitude at zero delay which obscured the tracking error. These results suggest that some patients with PD are able to utilize visual information for controlling tracking in this motor task in the same manner as healthy individuals.

Adult↗
PubMed1990

Red cell choline in spasmodic torticollis and in a monozygotic twin pair with Tourette's syndrome.

1. Alterations in cholinergic function may play a role in the pathophysiology of idiopathic spasmodic torticollis (ST) and Gilles de la Tourette's syndrome (GTS). We measured red blood cell (RBC) choline in (i) ST (n = 24) and paired controls matched for age and gender (ii) a 20-year old pair of monozygotic twins with GTS, one of whom was moderately affected (CV) and the other virtually recovered (DV) (iii) both parents of the GTS twins, using gas chromatography-mass spectrometry. 2. RBC choline decreased with age in control men (r = -0.76; p less than 0.01) but not in control women. 3. RBC choline (nmol/ml) was higher in control men (18.3 +/- 4.8, X +/- SD) vs control women (13.1 +/- 4.3) (p = 0.025). 4. There was no significant difference in RBC choline (nmol/ml) between ST patients (16.6 +/- 5.0) and controls (15.5 +/- 5.2). 5. The RBC choline values (nmol/ml) in the twins and parents were: 56.6 (CV), 58.3 (DV), 89.8 (father), 38.3 (mother) and in the controls (age 20-24) (n = 5) 18.2 +/- 3.6. 6. These data suggest (i) RBC choline is affected by age and gender (ii) RBC choline is unchanged in ST (iii) the regulation of RBC choline is under genetic control (iv) elevated RBC choline is not a state marker for GTS.

Adult↗
PubMed1990

Lack of association between two restriction fragment length polymorphisms in the genes for the light and heavy neurofilament proteins and Alzheimer's disease.

The etiology of Alzheimer disease (AD) remains unknown. The hypothesis of genetic factors playing a role in the causation of the disease, at least in its familial form, has been borne out by results showing linkage in several early-onset AD families to a locus on the proximal part of the long arm of chromosome 21. Linkage was not detected in several other families using the same markers. The metabolism of neurofilaments is perturbed in AD, as indicated by the presence of neurofilament epitopes in neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit in AD brain. To detect a possible anomaly that might relate to the disease, we have searched for an association between the genes for the light subunit and the heavy subunit of the neurofilament triplet, and AD. Genotypes for restriction fragment length polymorphisms (RFLP) at each of the two loci were determined for an AD group and a control group. Allelic frequencies at a TaqI-defined RFLP for the gene for the light neurofilament subunit were 0.70 for the 3.7 kb allele and 0.30 for the 2.9 kb allele. HincII detected an RFLP for the heavy neurofilament subunit gene with frequencies of 0.31 for the 18.0 kb allele and 0.69 for the 6.8 kb allele. Frequencies were found to be similar in the two groups for both light and heavy neurofilament subunit loci. Although it cannot be excluded that mutations at other sites of the neurofilament genes are relevant to AD, the data reported here do not support an association between these genes and the disease.

Adult↗