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Biomedical subjects

S Gilman

Publications and source records attributed to S Gilman.

At least 91 records · Page 5Linked to original sources
PubMed1993

Inhibitory and excitatory amino acid neurotransmitter binding sites in cynomolgus monkey (Macaca fascicularis) cervical spinal cord.

Autoradiography of inhibitory and excitatory amino acid neurotransmitter binding sites in the cervical spinal cord of M. fascicularis spinal cord revealed inhomogeneous distribution of all binding sites in spinal gray matter. Quisqualate-sensitive [3H]glutamate binding, [3H]MK-801 binding, benzodiazepine binding, kainate binding, and GABAB binding had highest levels in the superficial layers of the dorsal horn (laminae 1 and 2) and substantially lower levels in other laminae. [3H]Strychnine binding was more uniformly distributed throughout all laminae with highest levels in the superficial layers of the dorsal horn. These results are similar to those found in other mammals.

Animals↗
PubMed1993

Primate basal ganglia activity in a precued reaching task: preparation for movement.

Single cell activity was recorded from the primate putamen, caudate nucleus, and globus pallidus during a precued reaching movement task. Two monkeys were trained to touch one of several target knobs mounted in front of them after an LED was lighted on the correct target. A precue was presented prior to this target "go cue" by a randomly varied delay interval, giving the animals partial or complete advance information about the target for the movement task. The purpose of this design was to examine neuronal activity in the major structures of the basal ganglia during the preparation phase of limb movements when varying amounts of advance information were provided to the animals. The reaction times were shortest with complete precues, intermediate with partial precues, and longest with precues containing no information, demonstrating that the animals used precue information to prepare partly or completely for the reaching movement before the target go cue was given. Changes in activity were seen in the basal ganglia during the preparatory period in 30% of neurons in putamen, 31% in caudate nucleus, and 27% in globus pallidus. Preparatory changes were stronger and more closely linked to the time of movement initiation in putamen than in caudate nucleus. Although the amount of information contained in the precues had no significant effect on preparatory activity preceding the target go cue, a directional selectivity during this period was observed for a subset of neurons with preparatory changes (15% in putamen, 11% in caudate nucleus, 14% in globus pallidus) when the precue contained information about the upcoming direction of movement. A smaller subset of neurons showed selectivity for the preparation of movement amplitude. A larger number of preparatory changes showed selectivity for the direction or amplitude of movement following the target go cue than in the delay period before the cue. The intensity of preparatory changes in activity in many cases depended on the length of the delay interval preceding the target go cue. Even following the target go cue, the intensity of the preparatory changes in activity continued to be significantly influenced by the length of the preceding delay interval for 11% of changes in putamen, 8% in caudate nucleus, and 18% in globus pallidus. This finding suggests that preparatory activity in the basal ganglia takes part in a process termed motor readiness. Behaviorally, this process was seen as a shortening of reaction time regardless of precue information for trials in which the delay interval was long and the animals showed an increased readiness to move.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Pathologists' participation in postmortem examinations for patients with dementia.

Pathologists (n = 571) in Michigan were surveyed to examine the problem of limited access to autopsy experienced by families of patients with dementia and to assist with the implementation of the Michigan Dementia Program. The survey determined the extent to which pathologists performed autopsies for patients with dementia and/or were willing to do so as part of a statewide Postmortem Examination Program. Responses from 394 pathologists (69%) indicated that 49% were willing to perform brain removal and 44% were interested in learning more about the statewide program. The survey results were used to recruit pathologists, to identify potential problems, and to provide baseline data against which to measure the effects of a fully implemented program.

Attitude of Health Personnel↗
PubMed1993

Services for persons with dementia and their families: a survey of information and referral agencies in Michigan.

In planning a statewide Dementia Program, Michigan agencies (N = 244) providing geriatric information and referral (I&R) were surveyed to determine service availability, families' needs, and problems providing I&R for persons with dementia and their families. Home-delivered meals, nursing and social work assessments were considered more available. Medical assessment, however, was considered "very available" by only 60%. Respite and adult day care were least available and most needed. Least was known about autopsy and financial services. For several services, non-urban areas reported less availability than urban areas. With additional information and training, existing agencies could provide more available and extensive I&R for persons with dementia and their families, forming a statewide network.

Data Collection↗
PubMed1993

Neuropsychological deficits are correlated with frontal hypometabolism in positron emission tomography studies of older alcoholic patients.

In an extension of previous work, we studied the behavioral correlates of medial frontal lobe glucose hypometabolism in chronically alcohol-dependent patients. Thirty-one male patients who were detoxified, medically stable, and free of other central nervous system risk factors for neuropsychological impairment were examined with (1) anatomic imaging (CT or MR), (2) functional imaging with [18F] fluorodeoxyglucose (18F-FDG) and positron emission tomography (PET), and (3) a battery of neuropsychological tests, including two measures of abstraction known to be generally sensitive to frontal lobe disease or dysfunction [the Wisconsin Card Sorting Test (WCST) and the Halstead Category Test (HCT)]. 18F-FDG PET data from 18 age- and sex-matched normal control subjects were used for comparison. All patients met criteria for severe alcohol dependence and for at least a mild degree of alcoholic-induced cognitive impairment. Although the mean IQ level of the alcoholic patients was in the average range, the concepts attained and the error scores on the WCST and HCT were significantly impaired in comparison with established norms. Local cerebral metabolic rate for glucose (LCMRglc) was significantly decreased in a sagittal strip of the medial frontal cortex in the alcoholic patients as compared with the normal controls. Comparison of data from PET scans and anatomic images indicated that the reduced LCMRglc could not be attributed to reduced amounts of tissue alone. A statistically significant relationship was found between LCMRglc in the medial frontal region of the cerebral cortex and performance on the WCST, but not the HCT. These findings suggest that chronic alcohol intake results in impaired function of cerebral tissue in the medial frontal region.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

In vivo cerebral metabolism and central benzodiazepine-receptor binding in temporal lobe epilepsy.

Positron emission tomography measured interictal cerebral glucose metabolism with [18F]fluorodeoxyglucose and central benzodiazepine-receptor binding with [11C]flumazenil in 10 mesial temporal lobe epilepsy (TLE) patients and in normal subjects. Eight TLE patients had mesial temporal, lateral temporal, and thalamic hypometabolism ipsilateral to EEG ictal onsets, with additional extratemporal hypometabolism in four. One had unilateral anterior mesial temporal hypometabolism only, and one had normal metabolism. Each patient had decreased benzodiazepine-receptor binding in the ipsilateral anterior mesial temporal region, without neocortical changes. Thus, interictal metabolic dysfunction is variable and usually extensive in TLE, whereas decreased central benzodiazepine-receptor density is more restricted to mesial temporal areas. Metabolic patterns in TLE may reflect diaschisis, while benzodiazepine-receptor changes may reflect localized neuronal and synaptic loss that is specific to the epileptogenic zone. [11C]Flumazenil imaging may be useful in presurgical evaluation of refractory complex partial seizures.

Adult↗
PubMed1993

Perceptual analysis of speech disorders in progressive supranuclear palsy.

We used oral motor examinations and quantitative perceptual speech analysis to study deviant speech dimensions in 44 patients with progressive supranuclear palsy (PSP). All patients had dysarthria with variable degrees of spasticity, hypokinesia, and ataxia; 28 patients had all three of these components, and 16 patients had only two components. Twenty-two patients (50%) had predominantly spastic components, 15 (34%) had predominantly hypokinetic components, six (14%) had predominantly ataxic components, and in one (2%) the spastic, hypokinetic, and ataxic components were equal. Stuttering occurred in nine patients (20%) and palilalia in five (11%). The finding of a mixed dysarthria with a combination of spastic, hypokinetic, and ataxic components might assist in diagnosis and is consistent with the widespread neuropathologic changes found in PSP.

Aged↗
PubMed1992

GABAA, GABAB, and benzodiazepine binding sites in the cerebellar cortex of the red-eared turtle (Pseudemys scripta).

We used receptor autoradiography to ascertain the distribution of GABAA and GABAB binding sites in the cerebellar cortex of the red-eared turtle (Pseudemys scripta). GABAA binding sites were found in both molecular and granule cell layers with highest levels in the granule cell layer. GABAB binding sites were found at highest level in the molecular layer. Benzodiazepine binding sites were found in approximately equal abundance in both layers. Little binding of any ligand was seen in the Purkinje cell layer. Our results are similar to those found in mammals and other non-mammalian vertebrates and indicate that the organization of inhibitory pathways of the cerebellar cortex has been conserved in the course of vertebrate evolution.

Animals↗
PubMed1992

Progressive subcortical gliosis and progressive supranuclear palsy can have similar clinical and PET abnormalities.

In studies of cerebral glucose metabolism utilising positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose, patients with the clinical picture of progressive supranuclear palsy (PSP) have shown predominantly frontal glucose hypometabolism. This is presumed to represent deafferentation of cerebral cortical from subcortical structures. In these studies, however, the diagnosis of PSP has not been verified by pathological examination. Necropsy examinations were performed in three patients with the clinical features of PSP in whom PET had demonstrated predominantly frontal hypometabolism. In two of these patients the diagnosis of PSP was confirmed pathologically, and no morphological abnormalities were found in the cerebral cortex. The third patient had extensive cortical and subcortical neuronal loss and gliosis without neurofibrillary tangles, consistent with the diagnosis of progressive subcortical gliosis (PSG). Even in retrospect no unique clinical neurological abnormality or finding on laboratory investigation could be identified that distinguished this latter patient from those with pathologically confirmed PSP. We conclude that PSG and PSP may be indistinguishable during life, and necropsy confirmation is needed for definite diagnosis.

Blood Glucose↗
PubMed1992

Relation between hospital experience and in-hospital mortality for patients with AIDS-related Pneumocystis carinii pneumonia: experience from 3,126 cases in New York City in 1987.

There is marked debate about whether outcomes of care, particularly mortality, vary as a function of hospital and physician experience with a disease. This issue is especially important with respect to AIDS because greater than 200,000 individuals have now been diagnosed with this disease. We analyzed discharge data for 3,126 persons with AIDS who had Pneumocystis carinii pneumonia and who were treated at one of 73 New York City hospitals in 1987. In-hospital mortality was 25%. Factors associated with higher chances of short-term death were older age, being black, not having private health insurance, and being severely ill. A logistic regression model indicated that after controlling for differences in patient and hospital characteristics, the chances of death decreased when care was given at hospitals with higher caseloads of patients with Pneumocystis carinii pneumonia. Our findings suggest that hospital experience may decrease mortality in this subset of patients with human immunodeficiency virus disease, although it is unknown whether this is due to differences in quality of care.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Bursting properties of units in cat globus pallidus and entopeduncular nucleus: the effect of excitotoxic striatal lesions.

The bursting properties of units recorded in globus pallidus and entopeduncular nucleus were studied in awake cats sitting quietly before and after ipsilateral excitotoxic striatal lesions. A computerized statistical procedure was used to identify and evaluate bursts in the recorded spike trains. Bursts were assigned a quantitative statistical measure of burst 'strength' (or improbability) - the surprise value. Before the lesion, 34% of units in the globus pallidus and 60% of units in the entopeduncular nucleus exhibited bursts. Burst units had a significantly slower discharge rate and a significantly greater variability of discharge than non-burst units. The mean length of the interspike intervals immediately preceding the bursts was significantly longer than the overall median intervals in burst units. After the lesion, 21% of units in the globus pallidus and 11% of the units in the entopeduncular nucleus exhibited bursts. Burst units had significantly higher discharge rates and lower discharge variability after the lesion. In contrast, the lesion had no significant effect on the rate or variability of non-burst units. The differences between bursting and non-bursting units in discharge rate and variability disappeared after the lesion. In globus pallidus, the lesion resulted in a significant reduction in the mean number of bursts per unit, surprise value per burst, mean length of bursts, and number of spikes per burst, and a significant increase in the mean discharge rate of burst units. In entopeduncular nucleus, the small number of bursts recorded after the lesion precluded a useful statistical comparison of the effect of striatal lesions on the properties of the bursts. This study demonstrates that removing striatal projections to globus pallidus and entopeduncular nucleus decreases bursting in these nuclei, indicating that intact striatal projections are necessary for the normal production of bursts in these regions.

Animals↗
PubMed1991

The temporal structure of spike trains in the primate basal ganglia: afferent regulation of bursting demonstrated with precentral cerebral cortical ablation.

We studied the temporal pattern of discharge of single units in the basal ganglia of awake primates sitting quietly. Bursting was studied with a procedure that identified individual bursts in a spike train, quantifying burst intensity (surprise), bursts per 1000 spikes, spikes per burst and burst length. Autocorrelation techniques were used to assess the dependencies of spike trains on the temporal order of intervals. Striatal units had a greater tendency to burst (79% of units) than pallidal units (50%). The caudate nucleus and putamen had nearly identical burst properties on all measures. In the pallidum, bursting was more prevalent in the external segment and bursts were more intense and more frequent than in the internal segment. The autocorrelation analysis revealed that the temporal structure of the spike train was more dependent on the order of intervals in the striatum than in the pallidum. Bursting units had an increased probability of discharge after each spike and the relative refractory period was shorter in bursting units than units without bursts. Very few units exhibited cyclic discharge properties. Ablations of areas 4 and 6 in the precentral cortex demonstrated that striatal bursting was under afferent control. The putamen, which receives more cortical afferents from areas 4 and 6 than the caudate nucleus, had fewer and less intense bursts after the afferents were lesioned. Burst intensity did not change in the pallidum after the lesion. The findings indicate that bursting properties contribute to discharge variability in the basal ganglia and suggest that information transfer in the striatum may utilize bursts. In contrast, rate coding may be a more important mechanism for units in the pallidum.

Action Potentials↗
PubMed1991

Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy.

We examined binding to excitatory amino acid and inhibitory amino acid receptors in frozen hippocampal sections prepared from surgical specimens resected from 8 individuals with medically refractory temporal lobe epilepsy. The excitatory receptors studied included N-methyl-D-aspartate (NMDA), strychnine-insensitive glycine, phencyclidine, and quisqualate. The inhibitory receptors studied were gamma-aminobutyric acid type A (GABAA) and benzodiazepine. Excitatory and inhibitory amino acid receptor binding were differentially altered in the patients with temporal lobe epilepsy in comparison to 8 age-comparable autopsy control subjects, and changes in receptor binding were regionally selective in four areas. Binding to phencyclidine receptors associated with the NMDA channel was reduced by 35 to 70% in all regions in the hippocampi of the patients. In contrast, binding to the NMDA recognition site and its associated glycine modulatory site was elevated by 20 to 110% in the cornu ammonis (CA) 1 area and dentate gyrus of the hippocampus of the patients. Binding to these sites was unaffected in area CA4. Binding to the quisqualate-type excitatory amino acid receptor was unchanged in all regions except the stratum lacunosum moleculare CA1, where it was increased by 63%. GABAA and benzodiazepine receptor binding was reduced by 20 to 60% in CA1 and CA4, but unchanged in dentate gyrus. The data indicate that excitatory and inhibitory amino acid receptors are altered in the hippocampus of patients with temporal lobe epilepsy.

Adult↗
PubMed1990

Two types of quisqualate receptors are decreased in human olivopontocerebellar atrophy cerebellar cortex.

We used receptor autoradiography to study the distribution of ionotropic and metabotropic quisqualate (QA) receptors in normal human cerebellar cortex and cerebellar cortex from 7 cases of olivopontocerebellar atrophy (OPCA). In normal human cerebellar cortex, both types of QA receptors were densest in the molecular layer. Both ionotropic and metabotropic QA receptors were significantly diminished in the molecular layer of OPCA specimens. These results suggest that both ionotropic and metabotropic QA receptors are localized on Purkinje cell dendrites.

Autoradiography↗
PubMed1990

Autoradiographic localization of inhibitory and excitatory amino acid neurotransmitter receptors in human normal and olivopontocerebellar atrophy cerebellar cortex.

We used standard techniques of receptor autoradiography to study the distribution of inhibitory and excitatory amino acid neurotransmitter receptors in human normal cerebellar cortex. Benzodiazepine (BDZ) receptor density was relatively high in both granule cell and molecular layers. GABAA receptor density was highest in granule cell layer with lower receptor density in molecular layer. There was a lower density of GABAB receptors than GABAA receptors in both molecular and granule cell layers with a relatively higher density of GABAB receptors in molecular layer than in granule cell layer. In granule cell layer, the density of the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors was greatest whereas in molecular layer the quisqualate (QA) receptor subtype density was greatest. With [3H]N-(1-[2-thienyl]cyclohexyl)3-4-piperidine as a ligand, there was no specific binding to the phencyclidine receptor. Molecular layer was also characterized by relatively high density of a non-NMDA/non-QA displaceable glutamate binding site. We studied also the cerebellar cortex of 4 cases of olivopontocerebellar atrophy (OPCA), a syndrome in which Purkinje and granule cells degenerate. In these specimens, there was significant decrement of BDZ and GABAA receptors in both molecular and granule cell layers, with loss of GABAB receptors in molecular layer. NMDA receptors were depleted in granule cell layer while QA receptors and the non-NMDA/non-QA glutamate binding site were significantly depleted in molecular layer. Our normal human and OPCA data are largely consistent with animal data about the cellular localization of cerebellar cortical amino acid neurotransmitter receptors.

Autoradiography↗
PubMed1990

Spontaneous neuronal unit activity in the primate basal ganglia and the effects of precentral cerebral cortical ablations.

The discharge properties of single neuronal units in the putamen, caudate nucleus, and globus pallidus were studied in awake primates. The effects of restricted deafferentation of the striatum were determined by recording single unit activity in animals with unilateral ablation of areas 4 and 6 of Brodmann. The most striking change was on the regularity of unit firing in the putamen. Units in the normal putamen exhibited a wide range of firing rates and variability. In many units discharge rate was very slow. After the lesion, putaminal units discharged in steady spike trains with highly regular patterns of interspike intervals having on average a 63% reduction in the coefficient of variation. Contrary to expectations, average firing rates actually increased slightly (22%) from a median value of 4.88 Hz in controls to 5.95 Hz in lesioned animals. Although the rates and variability observed in lesioned animals completely overlapped the range of the sample observed in controls, the distributions were shifted such that there were more units with regular discharge patterns and slightly faster firing rates. The caudate nucleus showed no significant change in firing rate or variability. In the globus pallidus, firing rate decreased significantly in the internal segment, and both segments showed an increase in discharge variability. The findings demonstrate that the cerebral cortex strongly influences the spontaneous discharge properties in the basal ganglia. The effects on the variability of spontaneous activity are greater than on the maintenance of tonic firing.

Action Potentials↗