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Biomedical subjects

J S Wilson

Publications and source records attributed to J S Wilson.

At least 109 records · Page 6Linked to original sources

MPTP produces a pattern of nigrostriatal degeneration which coincides with the mosaic organization of the caudate nucleus.

In the normal dog we have found that cholinesterase and tyrosine hydroxylase (TH) histochemistry define a mosaic structure of the caudate nucleus that is similar to that described in other species. To determine if nigrostriatal afferents interlocked with this mosaic we injected dogs with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin specific to dopaminergic nigrostriatal cells. Alternate sections in the caudate nucleus stained for acetylcholinesterase, TH, and terminal degeneration revealed that the areas of densest degeneration were localized to the matrix, thereby outlining areas of much lighter degeneration which were coincident with the patches. This pattern of terminal degeneration suggests the existence of subcomponents of the dopaminergic nigrostriatal pathway, at least one of which might be selectively vulnerable to MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Chronic ethanol administration depresses fatty acid synthesis in rat adipose tissue.

Administration of ethanol as part of a nutritionally adequate liquid diet to female Wistar rats was found to depress markedly incorporation of labelled glucose into adipose-tissue acylglycerol fatty acids. Similar results with labelled pyruvate and acetate suggested inhibition of the fatty-acid-synthesis pathway at, or distal to, the acetyl-CoA carboxylase step. Activities of acetyl-CoA carboxylase and fatty acid synthetase were markedly lower in ethanol-fed animals. The activity of another lipogenic enzyme, phosphatidate phosphohydrolase, was not affected by chronic ethanol feeding. These findings suggest that chronic ethanol administration has marked effects on adipose-tissue lipogenesis.

Acetates↗

Alterations in synaptic membrane molecular order associated with alcoholization and protein deficiency in rats.

The effects of chronic alcoholization and protein deficiency on synaptic membrane characteristics were studied in rats fed the following four liquid diets for 4 weeks: a protein-deficient diet containing alcohol, a protein-deficient diet containing no alcohol, a non-protein-deficient diet containing alcohol and a non-protein-deficient diet containing no alcohol. A fluorescent probe, diphenylhexatriene (DPH), was used to estimate the fluidity of synaptic membranes and their sensitivity to the fluidizing effect of ethanol added in vitro, in concentrations ranging from 50 mM to 800 mM. Prior to in vitro addition of ethanol, the difference between the fluidity of synaptic membranes of alcoholized and non-alcoholized animals was significant for the two groups of protein-deficient animals but not for the two groups of non-protein-deficient animals. After in vitro addition of ethanol, the differences between the fluidity of synaptic membranes of the alcoholized and non-alcoholized animals were larger and more frequently significant for the protein-deficient animals than for the non-protein-deficient animals. In view of previous observations that rats fed a protein-deficient diet experience more severe withdrawal symptoms following alcoholization than rats fed a nutritionally adequate diet, the results of the present experiment lend additional support to the hypothesis that tolerance and dependence may be mediated by alterations in biomembrane characteristics.

Alcoholism↗

Combined effects of protein deficiency and chronic ethanol consumption on rat pancreas.

This study was performed in order to delineate the combined effects of protein deficiency and chronic ethanol ingestion on the rat pancreas. Rats fed ethanol in combination with protein-deficient diets developed marked steatosis, whereas alcohol ingestion with nutritionally adequate diets and protein deficiency alone each were associated with a more moderate degree of pancreatic lipid accumulation. On biochemical analysis, it was found that protein deficiency decreased pancreatic phospholipid content. Furthermore, both protein deficiency and chronic ethanol consumption increased pancreatic cholesteryl ester content, and their effects were additive. Functional changes were studied using isolated pancreative acini. Protein deficiency depressed the tissue content of lipase and the ability of pancreatic acini to secrete lipase. Chronic ethanol feeding increased lipase levels in the acini and also their secretory capacity. Thus, to the extent that enzyme accumulation in the pancreas plays a role in the pathogenesis of alcoholic pancreatitis, these results may explain the higher incidence of pancreatitis in well-nourished alcoholics that has been documented in dietary surveys.

Alcoholism↗

Periodic response difference in mouse epidermis chronically exposed to crude-oils or BaP: males vs. females.

Skin cancer has long been associated with industrial and environmental exposure to individual chemical compounds, complex chemical mixtures, X-irradiation and UV-irradiation. Skin carcinogenesis in animal models has been used as a toxicity assay and to study mechanisms of neoplastic progression. Using a mouse-skin carcinogenesis model, we conducted assays of tumorigenic activity using several crude oils and benzo[a]pyrene. During analysis of the data for assessment of tumor production by these compounds, differences were observed in male and female time-to-tumor values. There were 4 possible observations for males and females in each of the treatment groups: (1) no significantly different time-to-tumor values between the sexes; (2) accelerated or delayed response by one or the other sex; (3) production of a greater number of tumors in one or the other sex; and (4) production of different tumor types in one of the sexes. Our data show that 3 of these 4 do occur in mice epidermally-exposed to these compounds. There were groups with no differences between male/female response to treatment. Of specific interest were periodic male/female differences in time-to-time values. Only 1 compound, a shale-derived crude oil, produced tumors more extensively in one sex than the other. While benzo[a]pyrene produced predominantly carcinomas, the crude oils produced papillomas and carcinomas to varying degrees. However, the types of tumors produced showed no preference for one or the other sex. In the groups with different time-to-tumor values for male and female animals, the differences occurred either throughout the course of the experiment or in specific time domains. In 1 treatment group, the females had significantly earlier time-to-tumor values than males. In several of the other treatment groups the females had significantly longer time-to-tumor values. Of these treatment groups, the female mean time-to-tumor values were either cumulatively significantly longer or periodically delayed compared to the male values. The presence of significantly accelerated or delayed tumor production by one sex in these animal systems implies sex-related modulation of neoplastic progression.

Administration, Cutaneous↗

Sympathetic tone affects human limb vascular resistance during a maximal metabolic stimulus.

To evaluate the relationship between heightened sympathetic tone and maximal metabolic vasodilation, peak forearm blood flow (ml.min-1.100 ml-1) was measured plethysmographically in 18 volunteers after the release of 10 min of arterial occlusion (the peak reactive hyperemic blood flow response, RHBF) both before and after a stimulus to induce heightened sympathetic tone. The stimulus was the application of ice to the forehead for 90 s just before and during RHBF measurements. Mean arterial cuff blood pressure (MAP; mmHg) was calculated, and corresponding resistance (R; mmHg.ml-1.min.100 ml) was derived from blood pressure divided by RHBF. During ice application, blood pressure rose (pre 92 vs. post 115 ml/mmHg; P less than 0.05), peak RHBF was unchanged (pre 38.8 vs. post 36.4 ml.min-1.100 ml-1; not significant), but R during the maximal metabolic stimulus rose (pre 2.5 vs. post 3.2 mmHg.ml-1.min.100 ml; P less than 0.05). To examine the effects of heightened sympathetic tone on conduit vessels, simultaneous measurements of maximal metabolic blood flow (RHBF) and brachial artery Doppler velocity (V, cm/s) were conducted (n = 5) with and without ice applied to the forehead. Velocity rose by 70% as flow remained constant. Thus brachial artery area (area = flow/velocity) and diameter decreased substantially (20% decrease in diameter). The increase in R noted with ice was due to an alpha-mediated response, since the increase in R was blocked by oral prazosin (n = 6) and was unaffected by maneuvers to alter myogenic tone (n = 5). We conclude that maximal metabolic vasodilation can be counteracted to some extent by the effects of heightened sympathetic tone. Moreover, some of the interaction between these two opposing influences takes place at the arterial level.

Adult↗

Massive angiofibroma: a surgical approach and adjunctive therapy.

A case of "end-stage" juvenile angiofibroma is presented which, by physical airway obstruction, almost killed the patient before treatment. With preoperative, adjunctive hormonal and especially embolization therapy, complete surgical removal of a 160 gm tumor was facilitated, with relatively little blood loss. A lateral transfacial approach was used that maximized the exposure created by tumor growth and minimized risks of permanently arrested growth in the severely displaced and compressed maxilla. This approach should be limited to tumors of similar size, location, and configuration; the specific indication is spread into the parotid region and out beneath or through the peripheral facial nerve.

Adolescent↗

MPDP+ causes a non-reversible decrease in neostriatal synaptic transmission in mouse brain slice.

MPTP causes a Parkinson's disease-like syndrome in man and certain other animals. The toxic effect occurs if monoamine oxidase B is available, indicating that an MPTP metabolite may cause the toxic effect. We tested the effect of MPDP+, the first product of MPTP oxidation, and found that it, like MPTP, caused a non-reversible decrease in synaptic transmission in the mouse brain slice preparation. As the second oxidation product, MPP+ had been shown not to cause a similar, non-reversible decrease in synaptic transmission, MPDP+ is a better candidate for the role of toxic substance.

Animals↗

MPTP produces a mosaic-like pattern of terminal degeneration in the caudate nucleus of dog.

This paper describes the spatial pattern of terminal degeneration in the caudate nucleus and putamen of the dog following an injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Marked inhomogeneities in the filed of terminal degeneration were found in the head of the caudate nucleus, which are reminiscent of the fundamental patch/matrix organization of the striatum. Using MPTP as a selective lesioning method, our results provide further evidence that the dopaminergic, nigrostriatal projection has a heterogeneous organization.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

The incorporation of [myo-2-3H] inositol into phosphatidyl inositol of stimulated rat pancreas.

The 'phospholipid effect' involves agonist induced breakdown of phosphatidyl inositol (PI) or its phosphorylated derivates with increased incorporation of 32P or [myo-2-3H] inositol during resynthesis. In rat pancreas pancreozymin and bethanecol resulted in the standard dose dependent increased incorporation of 32P into PI which was paralleled by increased amylase secretion. By contrast the incorporation of [myo-2-3H] inositol into PI was significantly decreased by pancreozymin whereas bethanecol had no effect. However, pancreozymin caused a 30% decrease in labelled PI irrespective of whether it was prelabelled with 32P or [myo-2-3H] inositol. Thus in rat pancreas, pancreozymin resulted in the standard agonist induced breakdown of pre-labelled PI but inhibited the incorporation [2-3H-myo] inositol during the resynthetic phase.

Amylases↗

Preparation of viable single cell suspensions of tracheal epithelial cells.

This paper reports a procedure used for isolating the entire epithelial lining of the rat trachea. Isolated trachea was initially filled with 0.2% hyaluronidase and incubated at 37 degrees C for 30 min. Tracheas were flushed with medium and then reinflated with 0.5 microgram/ml cytochalasin B and re-incubated for 60 min. The tracheal lumens were again flushed and reinstilled with 24 iu/ml pronase and incubated for a further 30 min. The tracheas were flushed again and the cells removed enumerated and viability assessed by trypan blue dye exclusion. Cell yields (X 10(6)) from 30 consecutive Fischer 344 rats were 5.06 +/- 0.16 (s.e.m.) and the mean percentage of viable cells was 83.13 +/- 1.10 (s.e.m.). This cell yield was close to the estimated tracheal cell population (5.3 X 10(6)). The suspensions were predominantly single cells which apparently retained a normal ultrastructural appearance.

Animals↗

Decrease in lipogenesis and glucose oxidation of rat adipose tissue after chronic ethanol feeding.

This investigation was performed to determine whether chronic ethanol feeding affects adipose tissue lipogenesis and glucose metabolism. Female Wistar rats were pair-fed nutritionally adequate liquid diets containing ethanol as 36% of energy or an isocaloric amount of carbohydrate for 3 weeks. Chronic ethanol feeding resulted in a depression of adipose tissue lipogenesis as assessed by labeled glucose incorporation into glyceride glycerol and glyceride fatty acids. Glucose oxidation was also impaired after chronic ethanol feeding. Such changes may contribute to the postprandial hypertriacyglyceridemia observed in alcoholics.

Adipose Tissue↗

MPTP causes a non-reversible depression of synaptic transmission in mouse neostriatal brain slice.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) causes a Parkinson's disease-like syndrome. The mechanism of MPTP's neurotoxicity is unknown; however, one hypothesis is that MPP+ (1-methyl-4-phenylpyridinium), a product of MPTP's oxidation, is the neurotoxic agent. Using a mouse brain slice preparation we studied the effects of MPTP and MPP+ on synaptic transmission. We found MPTP caused a decrease in amplitude of an excitatory synaptic response not reversed by washing. This non-reversible action of MPTP was prevented by GBR-32 and pargyline. MPP+s caused a decrease in synaptic transmission, but this decrease was reversed by washing. The results suggest that the toxic effect of MPTP on synaptic transmission is not accounted for by the action of MPP+.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Isolation of viable type II alveolar epithelial cells by flow cytometry.

We developed a new method for isolating viable type II cells from fractionated and unfractionated lung cell suspensions by flow cytometry using acridine orange (AO). Fischer-344 rat lungs were dispersed into single-cell suspensions by a technique that yields a high number of cells (4-5 X 10(8) cells/lung, congruent to 85% viable), congruent to 11% of which are type II cells. Elutriated fractions from the lung cell preparation and parent, unfractionated cell suspensions were incubated with 1.0-0.02 micrograms/ml AO and analyzed by flow cytometry. Parameters analyzed included axial light loss (ALL) and red fluorescence (RF). Based on their unique RF, attributable to AO staining of type II cell lamellar bodies, and their ALL characteristics, type II pneumocytes were sorted from elutriated fractions to greater than 95% purity. Using the same approach, type II pneumocytes were sorted from unfractionated lung cell suspensions at greater than or equal to 85% purity. The viabilities of the type II alveolar epithelial cells isolated by this method range from 85% to 95%, and the ultrastructural features of the sorted cells were unaltered by AO labeling or sorting.

Acridine Orange↗

Surgery for the psyche: a longitudinal study of women undergoing reduction mammoplasty.

This study suggests that surgery is effective in relieving the psychological distress of women requesting reduction mammoplasty for minimal deformity. Eleven young women who applied for operation on the NHS completed measures of psychoneurosis, mood, self-esteem and body perception. Prior to operation they had a distorted body image, low self-esteem and abnormal psychoneurotic profiles. Following surgery body image returned to a normal range; their self-confidence, and view of their femininity and sexual attractiveness were also enhanced. Improvement was maintained during 6 months of follow-up. These results have implications for the NHS provision of cosmetic surgery for such patients.

Adolescent↗