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Biomedical subjects

S A Clark

Publications and source records attributed to S A Clark.

At least 55 records · Page 3Linked to original sources

Effect of metoprolol on serial measurements of exchangeable sodium, blood pressure, renin and pulse rate in spontaneously hypertensive rats.

The cardioselective beta-blocker metoprolol was mixed with the diet (6 mg metoprolol/g food) and given to 9 spontaneously hypertensive rats (SHR) for four weeks, while 9 other SHR were given the plain diet only and served as controls. All rats were also given 0.5% drinking saline labeled with isotope 22Na (37 kBq/1) to drink. Measurements of total exchangeable sodium, blood pressure, pulse rate and weight were performed before and repeatedly during treatment. Plasma renin activity was measured at the end of the study. Before treatment exchangeable sodium, blood pressure, pulse rate and weight were no different between the groups. Metoprolol reduced the pulse rate and prevented the usual blood pressure increase in SHR. Both groups gained weight similarly. Exchangeable sodium increased similarly in both groups along with the weight increase. Plasma renin activity was not significantly different in the two groups. Thus, chronic metoprolol treatment of SHR reduced blood pressure and pulse rate in SHR but did not lower plasma renin or cause measurable sodium or fluid retention.

Animals↗

Defenestration of hepatic sinusoids as a cause of hyperlipoproteinaemia in alcoholics.

The hepatic sinusoidal endothelium separates sinusoidal blood from hepatocytes; changes in the porosity of this endothelium may affect the passage of chylomicrons into hepatocytes and influence lipid metabolism. Chronic exposure to ethanol reduces the porosity of the endothelium; this mechanism may underlie the hyperlipoproteinaemia observed in some people who drink heavily.

Adult↗

Receptive fields in the body-surface map in adult cortex defined by temporally correlated inputs.

Receptive fields (RFs) obtained at specific cortical sites can be used to define a topographic map of the body surface in adult mammalian somatosensory cortex. This map is not static, and RFs at particular cortical sites can change in size and location throughout adult life. Conversely, the cortical loci at which a given skin surface is represented can shift hundreds of micrometres across the cortex in the koniocortical field, area 3b (refs 1-12). This plasticity suggests that RFs derive not from rigid anatomical connections, but by the selection of a subset of a large number of inputs. We have proposed that inputs are selected on the basis of temporal correlation 11-15. Here we test this idea by altering the correlation of inputs from two adjacent digits on the adult owl monkey hand by surgically connecting the skin surfaces of the two fingers (the formation of syndactyly). This manipulation increases the correlation of inputs from skin surfaces of adjacent fingers. The striking discontinuity between the zones of representation of adjacent digits on the somatosensory cortex disappeared. These results support the hypothesis that the topography of the body-surface map in the adult cortex is influenced by the temporal correlations of afferent inputs.

Animals↗

1,25(OH)2 vitamin D3 sites of action in spinal cord and sensory ganglion.

Autoradiographic studies revealed concentration of 3H 1,25(OH)2 vitamin D3 in nuclei of certain neurons in the spinal cord of adult and neonatal mice, fed a normal or a vitamin D deficient diet. Nuclear uptake and retention was strongest in motor neurons in lamina IX. Nuclear concentration also existed in neurons of lamina II, lamina VIII, lamina X and intermediate nucleus of the lateral column. The results indicate that these neurons are target neurons which contain nuclear receptors for 1,25(OH)2 vitamin D3. This suggests that 1,25(OH)2 vitamin D3 has direct genomic actions on the innervation of skeletal muscle by exerting related trophic, secretory, and electrophysiological effects. In addition, these data point to direct genomic actions of 1,25(OH)2 vitamin D3 on spinal sensory perception, and on certain autonomic functions. Nuclear binding in certain neurons in the peripheral ganglion of the trigeminal nerve further suggests that sensory perception is influenced by 1,25(OH)2 vitamin D3 not only at the level of the substantia gelatinosa, but also at the level of spinal ganglia.

Animals↗

Detection and quantification of microorganisms in a heterogeneous foodstuff by image analysis.

A relatively inexpensive image analysis system has been developed to semi-automate the detection and quantification of microbial growth in sections of food. A system based on an IBM PC compatible, with a frame store card, was programmed to scan Gram-stained sections using a motorized stage. Each field of view was thresholded after subtraction of a background image and the area between two thresholds measured. In the food studied it was found that, by using a size limit, it was possible to reduce the number of fields that needed to be examined by a microscopist to approximately 3% of those scanned. Visual examination was still required to distinguish bacterial cells from other stained objects which occasionally occur.

Algorithms↗

Effects of sodium intake and aldosterone on the renal pressure-natriuresis.

To study the effects of dietary sodium and plasma aldosterone on pressure-natriuresis (PN) we examined six groups of adult, male Sprague-Dawley rats. Group 1 received normal-sodium diet, group 2 high-sodium diet, and group 3 low-sodium diet for 3 wk; group 4 was given low sodium for 3 wk then high sodium for 3 wk; groups 5 and 6 received high sodium for 3 wk but during the 3rd wk were also given aldosterone by subcutaneous infusion to mimic the plasma aldosterone seen in groups 1 and 3, respectively. After the diets, rats were killed, and urinary sodium excretion, glomerular filtration rate (GFR), and calculated tubular sodium reabsorption (FRNa) were measured during stepwise increases in perfusion pressure in isolated perfused kidneys from each group. No significant differences in blood pressure were seen between any of the groups. The PN curves for groups 2 and 3 were significantly different (P less than 0.001) and shifted to the left and right of group 1, respectively. These shifts appeared to be the result of significant (P less than 0.001) differences in FRNa rather than changes in GFR. PN was not significantly different in groups 4 and 2, indicating that the effects of low-sodium diet were reversible. The infusion of aldosterone in groups 5 and 6 was associated with modest and significant (P less than 0.001) shifts, respectively, of the PN curve to the right of the curve of rats in group 2. In group 6 this shift appeared to be due to significant (P less than 0.001) changes in FRNa, so as to resemble that seen in low-sodium rats of group 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

Nicotine decreases the porosity of the rat liver sieve: a possible mechanism for hypercholesterolaemia.

Nicotine was fed to rats for 6 weeks, as a weight adjusted dose equivalent to that of a human being smoking 50 to 100 cigarettes per day. Those rats fed nicotine developed hypercholesterolaemia. Scanning electron microscopy showed the porosity of the hepatic sinusoidal endothelium of nicotine fed animals was about 40% that of control animals. The decline in porosity was found to be due to a reduction in diameter rather than number of fenestrae. We believe that this decreased hepatic sinusoidal porosity may alter cholesterol homeostasis by increasing the circulation time of chylomicron remnants too large to pass through the fenestrae. This phenomenon may be an aetiological factor in the known correlation between cigarette smoking, atherosclerosis, and coronary heart disease in humans.

Animals↗

The importance of peritoneal cytology in endometrial carcinoma.

From 1971-1986, peritoneal washings were obtained for cytologic examination at the time of primary exploratory laparotomy in 340 patients with endometrial adenocarcinoma. Seventy-two samples (21.2%) contained malignant cells. The finding of malignant cytology increased with stage of disease: stage I, 17%; stage II, 19.5%; stage III, 68.7%; and stage IV, 85.7% (P less than .001). In 248 patients with clinical stage I disease for whom uterine evaluation was complete, there was an increasing incidence of malignant cytology with increasing grade (P = .002), depth of myometrial invasion (P = .003), and adnexal spread (P less than .001). Twelve of 41 patients (29.3%) with clinical stage I and positive cytology developed recurrent disease, compared with six of 207 (2.9%) with negative cytology (P less than .001). Survival for all stages together was poorer in patients with positive washings than in those with negative washings (P less than .001). This difference in survival was also observed in patients with clinical stage I disease (P less than .001). Among patients with surgical stage I disease, disease-free survival was also superior in the group with negative cytology. In both clinical and surgical stage I, intra-abdominal recurrences were more common among patients with malignant peritoneal cytology.

Adenocarcinoma↗

Dietary sodium deprivation raises blood pressure in the rat but does not produce irreversible hyperaldosteronism.

It is reported that dietary deprivation of sodium in young rats produces changes of sodium balance and aldosterone excretion which persist when normal sodium intake is restored. To test this further, sodium intake was reduced 10-fold in rats. In the first experiment sodium intake was reduced for 5 weeks in rats aged 3 weeks. Systolic blood pressure, heart rate and plasma renin concentration increased and growth rate was reduced. Sodium intake was then increased for 10 weeks. Blood pressure, heart rate and plasma renin concentration fell and growth rate increased but body weight did not regain control values. As compared with controls, plasma concentrations of aldosterone and corticosterone did not increase after the 10-week period. Thus, sodium depletion did not produce an irreversible change in aldosterone but it did raise arterial pressure. Further experiments confirmed the pressor effect in young and adult rats. Blood pressure was measured in the tail in these experiments but the increase in pressure was not a technical artifact as measurements made in the tail correlated well with measurements made simultaneously by intra-arterial catheter. Catheters were inserted under general anaesthetic for this comparison of pressure and rats previously deprived of sodium showed a significantly higher mortality rate due to the anaesthesia and surgery involved. Thus, a 10-fold reduction of dietary sodium raises blood pressure in young and adult rats and it may increase mortality from a minor surgical procedure. It does not produce irreversible changes in aldosterone.

Aldosterone↗

1,25-Dihydroxyvitamin D3 target cells in immature pancreatic islets.

Target cells of 1,25-dihydroxyvitamin D3 were identified by autoradiography in islets from rats of different ages. Nuclei of pancreatic islet cells selectively concentrated 1,25-[3H]dihydroxyvitamin D3 but not 25-[3H]hydroxyvitamin D3 or 24,25-[3H]dihydroxyvitamin D3. Developmental studies of pancreatic islets indicated that target cells, as revealed by significant nuclear concentration of 1,25-[3H]dihydroxyvitamin D3, are present in islet cells of fetal rats. The percentage of islet cells that concentrated 1,25-[3H]dihydroxyvitamin D3 increased from 10 to 15% in the fetus to 60% at 1 day of age. Immunocytochemical staining indicated that insulin-containing cells but not glucagon or somatostatin cells concentrated 1,25-[3H]dihydroxyvitamin D3. Peak uptake of 1,25-[3H]dihydroxyvitamin D3 was calculated to be 400 pmol/mg DNA, with no significant difference in nuclear accumulation between islet cells from neonatal and adult rats or between islets in vivo and isolated islets in vitro. The results of these studies indicate that 1,25-[3H]dihydroxyvitamin D3 target cells are present in islets before pancreatic beta-cells are morphologically or functionally mature; islet beta-cells concentrate 1,25-dihydroxyvitamin D3, but not 25-hydroxyvitamin D3 or 24,25-dihydroxyvitamin D3. We conclude that only the 1,25-dihydroxyvitamin D3 metabolite of vitamin D is accumulated by nuclei of developing and mature beta-cells and suggest that 1,25-dihydroxyvitamin D3 plays a role in the maturation of islet beta-cells.

Animals↗

Effects of high dietary contents of calcium and phosphorus on mineral metabolism and growth of vitamin D-deficient suckling and weaned rats.

We have tested the hypothesis that normalization of the plasma calcium (Ca) and phosphorus (P) concentrations by dietary means in vitamin D-deficient rat pups will prevent rickets. From day 6 of pregnancy rats were given a vitamin D-free diet containing 1.6% Ca and 1.4% P (-D 1.6) which normalized plasma Ca during lactation. Pups weaned from these mothers, and continuing on the -D 1.6 diet until 56 days of age, had a mean plasma Ca value of 8.6 +/- 0.2 mg/dl and were not significantly different from pups fed a vitamin D-replete diet with 0.4% Ca and 0.4% P in the following parameters: body weight (mean +/- SE for -D 1.6 rats: 197 +/- 4 g), percent bone ash (53 +/- 0.5), and tibia epiphyseal cartilage width (385 +/- 26 micron). In contrast, pups consuming the vitamin D-free diet with 0.4% Ca and 0.4% P had plasma Ca of 4.9 +/- 0.2 mg/dl, body weight of 156 +/- 4 g, reduced bone ash (45 +/- 0.5%) and abnormally wide epiphyseal cartilage (727 +/- 113 micron). Thus, elevating the plasma Ca level of vitamin D-deficient rat pups by dietary means can normalize body weight, epiphyseal cartilage width and bone mineral content.

Animals↗

Experimental laser-assisted end-to-side microvascular anastomosis.

The authors present a new technique of end-to-side microvascular anastomosis in a rat carotid artery model, employing a milliwatt CO2 laser. Both carotid arteries were isolated and approximated in an end-to-side fashion by the placement of four 10-0 nylon stay sutures. The milliwatt CO2 laser was used to effect vessel anastomosis between the sutures, using 70-100 mW of power. Animals were killed 8 weeks postoperatively. Angiography of each anastomosis was performed in all animals. All anastomoses were then harvested, and submitted for histological analysis. Anastomotic patency was 100%, both intraoperatively and angiographically. There was no evidence of intravascular thrombus, anastomotic stenosis, or pseudoaneurysm formation. Early in the experiment, some anastomoses showed localized dilatation at the anastomotic site. The histologic changes at the anastomotic site are described. Laser-assisted microvascular anastomosis is a feasible technique, and a potential alternative to conventional suture techniques.

Animals↗

The adrenal: a new target organ of the calciotropic hormone 1,25-dihydroxyvitamin D3.

Target cells for 1,25-dihydroxyvitamin D3 were demonstrated in the adrenal medulla by frozen-section autoradiography. The appearance of these target cells was age-dependent in neonatal mice. Immunocytochemical staining for phenylethanolamine-N-methyltransferase revealed that both epinephrine and non-epinephrine cells concentrate 1,25-dihydroxyvitamin D3 in their nuclei. In contrast, immunocytochemical staining for "vitamin D-dependent calcium-binding protein" (D-CaBP) demonstrated that D-CaBP immunoreactivity is localized in only a small percentage of adrenomedullary cells, in mice and rats. Comparison of PNMT and D-CaBP immunoreactivities in sequential sections showed that epinephrine-producing cells do not contain D-CaBP. These results indicate that adrenal medullary cells have receptors for 1,25-dihydroxyvitamin D3 and that 1,25-dihydroxyvitamin D3 may directly affect certain functions of these endocrine cells.

Adrenal Medulla↗

Serum fructosamine and glycated haemoglobin measurements in diabetic control.

Serum fructosamine and glycated haemoglobin (HbA1) were measured in capillary samples from diabetic children and compared with samples from non-diabetic children. Glycaemic control was assessed clinically and by average daily glucose values recorded by home monitoring. Fructosamine correlated with HbA1 and with average glucose values measured over 30 days. HbA1 also correlated with average glucose values measured over 60 days. Changes in fructosamine with time tended to parallel those of HbA1, and advance indication of deteriorating or improving glycaemic control was possible by observing changes in these. Fructosamine has many advantages over HbA1 measurement such as speed, technical ease, and low cost, and is a reliable alternative to HbA1 estimation as an indication of glycaemic control.

Adolescent↗