Parkinson's disease and dementia.
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Biomedical subjects
Publications and source records attributed to R Cash.
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[3H]Imipramine binding was studied in the prefrontal cortex and putamen of post-mortem brains from control and Parkinsonian subjects. Saturation and inhibition curves showed both high affinity [3H]imipramine binding related to the serotonin uptake mechanism and low affinity binding which was sodium-independent and unrelated to serotonergic uptake. After subcellular fractionation, high affinity [3H]imipramine binding sites were enriched in synaptosomal fractions. In Parkinson's disease, where brain serotonin concentrations are decreased, there was a significant reduction in the density of the high affinity binding in the prefrontal cortex and putamen while the characteristics of the low affinity binding sites remained unchanged. After subcellular fractionation of the putamen of Parkinsonian patients, the decrease in [3H]imipramine binding was found predominantly in the synaptosomal fractions. These results are consistent with a relation between the high affinity [3H]imipramine binding sites and the neuronal serotonin uptake mechanism. Estimation of [3H]imipramine binding could be used as a specific marker for the study of serotonergic innervation in human post-mortem material. The reduction in the density of tricyclic antidepressant binding sites found in cortical and subcortical areas of Parkinsonian brains may be somehow implicated in the depression often seen in patients.
The binding of adrenergic ligands (3H-prazosin, 3H-clonidine, 3H-dihydroalprenolol) was studied on a preparation of cerebral microvessels in the prefrontal cortex and putamen of control and Parkinsonian subjects. The adrenergic receptor density in microvessels of control patients was less than 0.5% and 3.3% respectively of the total binding. A significant decrease in the number of alpha-1 binding sites was observed on microvessels in the putamen of patients with Parkinson's disease.
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The binding of three adrenergic ligands ([3H]prazosin, [3H]clonidine, [3H]dihydroalprenolol) was studied in the frontal cortex of human brain. alpha 1-Receptors, labeled by [3H]prazosin, predominated. [3H]Clonidine bound to two classes of sites, one of high affinity and one of low affinity. Guanosine triphosphate appeared to lower the affinity of [3H]clonidine for its receptor. [3H]Dihydroalprenolol bound to three classes of sites: the beta 1-receptor, the beta 2-receptor and a receptor with low affinity which represented about 40% of the total binding, but which was probably a non-specific site; the beta 1/beta 2 ratio was 1/2.
Alpha 1, alpha 2, beta 1 and beta 2 adrenergic receptors were measured in the pre-frontal cortex of parkinsonian patients post-mortem. The number of beta 2 receptors was the same in control and parkinsonian subjects. alpha 1 and beta 1 receptors increased in number, particularly in demented parkinsonian patients, while alpha 2 receptors decreased. The affinity constants were unchanged. The modifications seem to be related to lesion of the noradrenergic pathway from the locus coeruleus to the cortex. The relationship between this lesion and the symptoms of dementia and depression in parkinsonian patients is discussed.
Three children with acrodermatitis enteropathica (AE) were treated with oral zinc dipicolinate (zinc-PA). The daily dose of zinc required to prevent exacerbations, when administered as the dipicolinate complex, was one-third the minimum amount of zinc required as the sulfate salt. The concentration of picolinic acid in the plasma of asymptomatic children with AE was significantly less than that of normal children. However, oral treatment with PA alone was ineffective. The plasma of the three AE children contained a measurable quantity of kynurenine which was undetectable in plasma from normal children. Absorption of an oral zinc load was normal. The results support the hypothesis that the genetic defect in AE is in the tryptophan pathway, although the role of PA in zinc metabolism remains to be defined.
Three patients who appear to have a previously undescribed congenital neuropathy are described. None is of Ashkenazi Jewish extraction, but each seems to fulfill the clinical diagnostic criteria for familial dysautonomia. All lack overflow tears, fungiform papillae, and deep-tendon reflexes; intradermal administration of histamine did not produce an axon flare. Intraocular instillation of dilute mecholyl produced miosis in the one patient tested. In contrast to patients with familial dysautonomia, the three patients had universal loss of pain sensation, profound hypotonia, and unusual facies. Pathologic examination of the sural nerve in one patient was not consistent with the usual findings in familial dysautonomia. These patients are believed to have a previously undescribed congenital neuropathy.
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Anesthetized young rabbits were ventilated for 6 hr at 20 cm H2O peak airway pressure using air nebulized with water at 22 degrees C (cold nebulized group, n = 11), at 36 degrees C (warm nebulized group, n = 11) and humidified air at 36 degrees C (warm humidified group, n = 10). Their biochemical status during ventilation and pulmonary morphology at autopsy were compared to those of ten control rabbits. Both nebulized groups had particulate water in the inspired air and water of condensation in the endotracheal tube. The rabbits ventilated with warm humidified air and the control group breathing spontaneously maintained their blood pressure and pHa within physiologic range. Rabbits ventilated with air nebulized with water at 22 and 36 degrees C had a significant decline in mean blood pressure (96 mm Hg leads to 61 mm Hg in cold nebulized and 91 mm Hg leads to 61 mm Hg in warm nebulized) and mean pHa (7.43 leads to 7.23 in cold nebulized and 7.42 leads to 7.31 in warm nebulized). All rabbits in the control and warm humidified groups survived the study whereas 9 of 22 in the nebulized groups died before completion of study (P < 0.005). Morphometric analysis revealed a significant increase in the mean vascular wall thickness in both nebulized groups of rabbits when compared to that in the control and warm humidified groups (P < 0.05). The cold nebulized group also had significantly less air space and correspondingly more interstitial thickness and intraalveolar edema (P < 0.05) compared to control and warm humidified groups. These findings of pulmonary parenchymal damage in rabbits ventilated with air containing particulate water and the greater degree of both physiologic and anatomic change evident in the cold nebulized animals suggest that particulate water and low inspired air temperature may contribute to the genesis of pulmonary damage during intermittent positive pressure ventilation.
Certain receptors in the duodenal mucosa respond to the osomotic effects of the digestion products of dietary carbohydrates and proteins with a resultant slowing of gastric emptying. Other receptors respond to the soaps formed during the digestion of fats. The relative effectiveness of these two sets of receptors is such that foods with equal energy produce equal slowing of gastric emptying. Thus the rate of delivery of energy to the duodenum, and hence to the blood, can be regulated without the energy having been directly measured. The results in the literature that we have examined are consistent with this duodenal system playing some part in the regulation of food intake.
An investigation of gastric emptying suggested that people choosing an energy-dense mixture of dood and drink have an empty stomach sooner--and might, therefore, eat more--than people who take their energy in more dilute form. Support for the notion that energy density (kcal divided by volume of food and drink) might be related to relative body-weight comes from a study in healthy males. A proportion, albeit a small one, of the variance in relative body-weight (Quetelet) could be ascribed to energy density, and the relationship was stronger among the more obese men.
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Explore the source record for details and available documents.