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Biomedical subjects

M D Wilson

Publications and source records attributed to M D Wilson.

At least 73 records · Page 4Linked to original sources
PubMed1989

Studies on the expression of genes encoding apolipoproteins B100 and B48 and the low density lipoprotein receptor in nonhuman primates. Comparison of dietary fat and cholesterol.

African green monkeys were fed diets containing low and moderate cholesterol concentrations with either polyunsaturated or unsaturated fat as 40% of calories. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol, and apoB concentrations generally were higher in animals fed (a) the higher dietary cholesterol concentration and (b) saturated fat. At necropsy, liver and intestine were removed, and measurement of mRNAs for LDL receptors (liver) and for apolipoprotein B (liver and intestine) was done. Monkey small intestine mucosa made exclusively apoB48 while the liver made only apoB100, although apoB mRNA in both tissues was the same size (14 kilobases). No dietary cholesterol or fat effects were found for apoB mRNA abundance in the liver, while the animals fed the higher dietary cholesterol level had 50% lower levels of hepatic LDL receptor mRNA. In a separate group of animals, livers were perfused and the rate of apoB secretion was measured. No dietary fat effect on apoB secretion rate was found, and no relationship between plasma LDL cholesterol concentration and the rate of hepatic apoB production existed. These findings support the idea that the dietary factors that increase LDL concentrations act by reducing clearance of apoB-containing particles rather than by increasing production of these lipoproteins. Hepatic LDL receptor mRNA was similar in abundance in polyunsaturated fat and saturated fat-fed animals, suggesting that the difference in plasma cholesterol concentration between these groups is not mediated via effects on LDL receptor mRNA abundance. The level of intestinal apoB mRNA was about 30% higher in animals fed the moderate dietary cholesterol concentration. Earlier studies have shown that more cholesterol is transported in chylomicrons from the intestine when dietary cholesterol levels are higher, and the increased intestinal apoB mRNA abundance may reflect increased intestinal cholesterol transport and chylomicron apoB48 production.

Animals↗
PubMed1989

Fish oil decreases hepatic cholesteryl ester secretion but not apoB secretion in African green monkeys.

Two groups of African green monkeys were fed diets containing 40% of calories as fat with half of the fat calories as either fish oil or lard. The fish oil-fed animals had lower cholesterol concentrations in blood plasma (33%) and low density lipoproteins (LDL) (34%) than did animals fed lard. Size and cholesteryl ester (CE) content of LDL, strong predictors of coronary artery atherosclerosis in monkeys, were significantly less for the fish oil-fed animals although the apoB and LDL particle concentrations in plasma were similar for both diet groups. We hypothesized that decreased hepatic CE secretion led to the smaller size and reduced CE content of LDL in the fish oil-fed animals. Hepatic CE secretion was studied using recirculating perfusion of monkey livers that were infused during perfusion with fatty acids (85% 18:1 and 15% n-3) at a rate of 0.1 mumol/min per g liver. The rate of cholesterol secretion was less (P = 0.055) for the livers of fish oil versus lard-fed animals (3.3 +/- 0.5 vs. 6.0 +/- 1.2 mg/h per 100 g, mean +/- SEM) but the rate of apoB secretion was similar for both groups (0.92 +/- 0.15 vs. 1.01 +/- 0.13 mg/h per 100 g, respectively). The hepatic triglyceride secretion rate was also less (P less than 0.05) for the fish oil-fed animals (8.3 +/- 2.5 vs. 18.3 +/- 4.4 mg/h per 100 g). Liver CE content was lower (P less than 0.006) in fish oil-fed animals (4.1 +/- 0.8 vs. 7.4 +/- 0.7 mg/g) and this was reflected in a lower (P less than 0.04) esterified to total cholesterol ratio of perfusate VLDL (0.21 +/- 0.045 vs. 0.41 +/- 0.06). The hepatic VLDL of animals fed fish oil had 40-50% lower ratios of triglyceride to protein and total cholesterol to protein. From these data we conclude that livers from monkeys fed fish oil secreted similar numbers of VLDL particles as those of lard-fed animals although the hepatic VLDL of fish oil-fed animals were smaller in size and relatively enriched in surface material and depleted of core constituents. Positive correlations between plasma LDL size and both hepatic CE content (r = 0.87) and hepatic VLDL cholesterol secretion rate (r = 0.84) were also found.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗
PubMed1987

Bioaccumulation factor for 32P measured in bluegill, Lepomis macrochirus, and catfish, Ictalurus punctatus.

The ratio of the bioaccumulation factors for 32P and phosphorus was determined for edible tissue in two species of freshwater fish by measuring the specific activity (32P activity per milligram phosphorus) in muscle relative to feed. The 32P tracer was added to the feed at a uniform level throughout the study. Feeding was at two levels: ad libitum and at a lower but constant intake per body weight. In the main experiment, bluegill were maintained in a large flow-through tank and sacrificed at approximately weekly intervals for 51 d of 32P accumulation and 28 d of depuration to compare the specific activity with values predicted with a calculational model. In experiments performed in smaller aquaria, the specific activity in bluegill and catfish muscle was compared at two feeding levels and two temperatures. In addition, unfed fish were exposed to 32P in water at a known specific activity to determine the extent of phosphorus uptake directly from water. The pattern of specific activity increase and decrease in fish muscle during the accumulation/depuration experiment was consistent with a one-compartment model, so that specific activity ratios at steady state could be predicted from measurements during relatively brief exposures. On this basis, the ratio of the bioaccumulation factors of 32P and phosphorus in fish feeding ad libitum was 0.081 for bluegill and 0.17 for catfish. Hence, at a mean phosphorus bioaccumulation factor of 70,000, the factors for 32P are 6,000 and 12,000, respectively. The ratios were less at lower phosphorus intakes associated with lower feeding rates; moreover, the lesser value for bluegill occurred at a much lower phosphorus intake than by catfish. The bioaccumulation factor ratio was lower by an order of magnitude at a water temperature of 11 degrees C than at 16-27 degrees C, and was lower by two orders of magnitude when phosphorus uptake was from water by unfed fish.

Animals↗
PubMed1987

Effect of bromocriptine on LH pulsatility in the polycystic ovary syndrome.

The effects were studied of bromocriptine, 10 mg daily for 1 year, on luteinizing hormone (LH) pulse characteristics in patients with classical polycystic ovarian syndrome (PCOS). All patients were hirsute, had been oligomenorrhoeic since menarche, had LH: FSH ratios of greater than 3:1, and either elevated serum testosterone (T) or dehydroepiandrosterone sulphate (DHAS) concentrations. In 10 subjects who completed the study menstrual frequency increased from an average of 3.6 to 8 per year but few of the cycles were ovulatory. Mean (SE) serum testosterone fell from 4.4 (0.5) nmol/l pretreatment to 2.8 (0.3) nmol/l (P less than 0.01) and DHAS from 7.9 (1.1) mumol/l to 5.4 (1.1) mumol/l (P less than 0.05). Serum delta 4 androstenedione and oestradiol did not change with bromocriptine treatment. Mean serum LH fell from 17.4 (2.4) IU/l to 11.2 (1.8) IU/l (P less than 0.03) after 12 months of bromocriptine. No pattern of LH pulsatility specific to PCOS was detected during 10 min sampling for an 8 h period prior to dopamine agonist treatment. LH interpeak interval (58 (5.2) min) and peak amplitude (156 (7.2%) of mean nadir) in untreated PCOS were similar to that of the mid-follicular stage of ovulatory cycles, and bromocriptine for 1 year did not alter these variables. We conclude that while bromocriptine reduces serum androgen levels and increases menstrual frequency it has no effect centrally to modify hypothalamic GnRH secretion. The reduction in LH levels by bromocriptine may be the result of diminished gonadotroph sensitivity to GnRH or reduced pituitary stores of LH available for release. Despite the return towards normal of various hormonal characteristics of PCOS, bromocriptine has little place in the management of this condition.

Adolescent↗
PubMed1986

Inhibition of liver lipogenesis by dietary polyunsaturated fat in severely diabetic rats.

Diabetic and nondiabetic rats were used to ascertain if dietary polyunsaturated fats inhibited hepatic acetyl-CoA carboxylase and fatty acid synthetase in insulin-insufficient rats as had been previously shown for normal rats. Male rats were rendered diabetic (400-600) mg glucose/100 mL blood) with streptozotocin and were fed a high fructose fat-free diet. Safflower oil or palmitate (or tallow) was added to the basal fructose diet at a level to supply 12,24 or 36% additional digestible energy. Compared with normal rats, diabetic rats had significantly lower hepatic fatty acid biosynthesis, but the proportion of acetyl-CoA carboxylase expressing catalytic activity as determined by the avidin-inactivation technique was unaffected by diabetes. Diabetes did not lower the maximal maximal activities of carboxylase and fatty acid synthetase. Moreover, the activities of these enzymes greatly exceeded the rate of fatty acid synthesis. At all levels of fat supplementation, the high linoleate safflower oil consistently resulted in a 50% lower rate of fatty acid biosynthesis than did comparable levels of tallow or palmitate. Safflower oil was also a more effective suppressor of the activities of acetyl-CoA carboxylase and fatty acid synthetase than the saturated fats. Our data suggest that the greater inhibition of hepatic fatty acid biosynthesis by polyenoic fatty acids is an insulin-independent mechanism.

Acetyl-CoA Carboxylase↗
PubMed1984

Resistance of lung fatty acid synthesis to inhibition by dietary fat in the meal-fed rat.

One-half of the palmitate utilized by the lung for production of the surfactant phospholipid, dipalmitoyl phosphatidylcholine, originates from de novo palmitate synthesis in the lung. In this report the lung was examined for the influence of dietary fat on the lung de novo fatty acid synthesis pathway. Lung lipogenesis was reduced by fasting and accelerated by carbohydrate refeeding or insulin injection. However, in general lung fatty acid synthesis was unaffected by dietary fat. Supplementing one meal (high glucose diet) with as much as 36% additional fat kilocalories did not suppress lung fatty acid synthesis. An inhibition of fatty acid synthesis resulted from a fat supplement of +60 and +120% of meal kilocalories, but this inhibition was likely due to an attenuated rate of glucose absorption. Ingestion of a high carbohydrate diet supplemented with 10, 17, or 30% added kilocalories as safflower oil or palmitate had no effect on lipogenesis after 10 days. On the other hand, liver fatty acid synthesis and acetyl-CoA carboxylase were selectively suppressed by safflower oil, whereas dietary palmitate was ineffective as an inhibitor of lipogenesis. These data clearly demonstrate that the well-characterized preferential suppression of liver lipogenesis by dietary polyunsaturated fats does not extend to lung tissue, and, more importantly, the inhibition of liver lipogenesis is not secondary to an essential fatty acid deficiency. The marked resistance of lung fatty acid synthesis to inhibition by dietary fat might be a biological protective mechanism to ensure adequate palmitate for dipalmitoyl phosphatidylcholine synthesis.

Acetyl-CoA Carboxylase↗
PubMed1983

Evaluation of an isotope ratio method for measuring biliary cholesterol secretion.

We have evaluated an isotope ratio method for measuring biliary cholesterol secretion. Secretion was measured in eight nonhuman primates by analysis of radioactivity of feces and plasma 4 weeks after intravenous administration of a single dose of [3H]cholesterol. For the test, [14C]cholesterol was fed in known amounts daily for 10 days. The ratio of isotopes in feces (14C/3H) was equivalent to the ratio of total radioactivity that entered the intestine from diet and bile. Assuming biliary cholesterol specific activity equals plasma cholesterol specific activity, the mass of cholesterol secreted daily in the bile could be calculated. In paired experiments in four animals we were able to directly compare biliary secretion by the new method with mass measurement by intraduodenal intubation (Grundy, S. M., and A. L. Metzger. 1972. Gastroenterology. 52: 2100-1216). The two methods correlated well in these four animals (r = 0.97). We further noted that bile secretion by the new method (eight animals) and by the mass method (four animals) correlated well with body weight (r = 0.94 for weight vs secretion by the isotope ratio method; r = 0.97 for weight vs secretion by the mass ratio method). Ranges of body weight and secretion for the eight animals were 4.2-13.1 kg and 3.6-11.4 mg/hr, respectively. The slopes of the two regression lines for body weight vs. secretion measured by the two methods did not differ significantly from one another (F(1.8) = 1.42; 0.25 less than P less than 0.50).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Coordinate suppression of liver acetyl-CoA carboxylase and fatty acid synthetase by polyunsaturated fat.

Polyunsaturated fats (PUFA) suppressed hepatic fatty acid synthesis and the activities of lipogenic enzymes more effectively than did saturated fats. The activity of glycolytic enzymes--glucokinase, phosphofructokinase and pyruvate kinase--were not affected by PUFA. The absolute rate of liver fatty acid synthesis after meal ingestion was very similar to the maximal activities of acetyl-CoA carboxylase and fatty acid synthetase. When PUFA was supplemented to a fat-free diet, the activities of carboxylase and synthetase decreased similarly over 3 days. During the 3 days, the concentration of liver malonyl-CoA (after meal ingestion) did not significantly differ between the fat-free and PUFA dietary treatments. Apparently PUFA feeding caused a coordinate decrease in the utilization and production of malonyl-CoA which resulted in no net change in malonyl-CoA pool size. Thus the mechanism by which PUFA suppresses fatty acid synthesis appears to be by coordinately and specifically reducing the amount of carboxylase and fatty acid synthetase.

Acetyl-CoA Carboxylase↗
PubMed1973

A procedure for increasing oral reading rate in hard-of-hearing children.

This study investigated the effects of systematic training on the oral reading rate of four hard-of-hearing children. In training, systematic increases in pulsing rate of a vibrotactile stimulus were arranged. The children received points, exchangeable for money when their reading rate equalled the pulse rate of the stimulus. The training procedure was effective in increasing the oral reading rate in all children. Generalized increases in reading rate on untrained word lists, sentences, and paragraphs were also observed.

Journal Article↗
PubMedDate not supplied

Deforestation and the spatio-temporal distribution of savannah and forest members of the Simulium damnosum complex in southern Ghana and south-western Togo.

Spatio-temporal data on cytotaxonomic identifications of larvae of different members of the Simulium damnosum complex collected from rivers in southern Ghana and south-western Togo from 1975 until 1997 were analysed. When the data were combined, the percentages of savannah blackflies (S. damnosum sensu stricto and S. sirbanum) in the samples were shown to have been progressively increasing since 1975. The increases were statistically significant (P < 0.001), but the rates of increase were not linear. Further analyses were conducted according to the collection seasons and locations of the samples, to account for possible biases such as savannah flies occurring further south in the dry season or a preponderance of later samples from northern rivers having more savannah flies. These analyses showed that the increasing trend was statistically significant (P < 0.0001) only during the periods April to June and October to December. The presence of adult savannah flies carrying infective larvae (L3) indistinguishable from those of Onchocerca volvulus in the study zone was confirmed by examinations of captured flies. The percentages of savannah flies amongst the human-biting populations and the percentages with L3s in the head were higher during dry seasons than wet seasons and the savannah species were found furthest south (5 degrees 25'N) in the dry season. Comparisons of satellite images taken in 1973 and 1990 over a study area in south-western Ghana encompassing stretches of the Tano and Bia rivers demonstrated that there have been substantial increases in urban and savannah areas, at the expense of forest. This was so not only for the whole images but also for subsamples of the images taken at 1, 2, 4, 8 and 16 km distant from sites alongside the River Tano. At every distance from the river, the percentages of pixels classified as urban or savannah have increased in 1990 compared with 1973, while those classified as degraded or dense forest have decreased. The possibility that the proportionate increases in savannah forms of the vectors of onchocerciasis, and hence in the likelihood of the transmission of savannah strains of the disease in formerly forested areas, were related to the decreases in forest cover is discussed.

Animals↗
PubMedDate not supplied

Determination of ambulatory blood pressure control in treated patients with controlled office blood pressures.

Office blood pressure measurement is the standard for assessing blood pressure control. Many patients, however, take their antihypertensive medication in the morning, so they are likely to have their office blood pressure measured during the maximal antihypertensive effect. It is therefore unknown whether patients deemed by office blood pressure to be controlled do in fact have 24h blood pressure control. The objectives of this study were to determine blood pressure control, including blood pressure control while the patients were awake and during the first 6 hours after awakening, by ambulatory blood pressure monitoring (ABPM) in treated hypertensive patients deemed by office blood pressure measurements to be controlled. A total of 103 patients on a stable antihypertensive regimen and deemed to be controlled in terms of office blood pressure values (mean office blood pressure <140/90mmHg) were enrolled. Patients were stratified by cardiovascular risk status and the number of antihypertensive medications that they were taking. Seventy-eight out of 103 participants successfully completed ABPM. The mean ambulatory blood pressure was greater than 135/85mmHg and 140/90mmHg while awake for 37% (95% confidence interval [CI] 26-48%) and 23% (95% CI 14-32%) of all patients respectively. Forty-eight per cent (95% CI 33-63%) of patients taking monotherapy versus 25% (95% CI 11-39%) of patients on multiple antihypertensive medications were uncontrolled (P=0.039) using 135/85mmHg as the reference value. Thirty-one per cent (95% CI, 17-44%) of patients on monotherapy versus 14% (95% CI 3-25%) of patients on multiple antihypertensive medication were uncontrolled (P=0.064) using 140/90mmHg instead. These results demonstrate that a high number of patients deemed by office blood pressure to be under control do not have adequate blood pressure control based on ABPM.

Adult↗
PubMedDate not supplied

Current issues in treating the hypertensive patient with diabetes: focus on diabetic nephropathy.

OBJECTIVE: To review the pathophysiology of hypertension and complications in patients with diabetes mellitus, specifically focusing on diabetic nephropathy; to evaluate the current clinical literature regarding the appropriate management of hypertension in this patient group; and to offer treatment recommendations. DATA SOURCES: A MEDLINE search of applicable English-language clinical studies, abstracts, and review articles pertaining to hypertension, diabetes, and diabetic nephropathy. STUDY SELECTION: Relevant studies on humans, examining hypertension, diabetes, and diabetic nephropathy, and the effects of drug therapy on these interrelated disease states. DATA SYNTHESIS: Pathophysiology of hypertension in the patient with diabetes mellitus and the pathophysiology of diabetic nephropathy are discussed. Studies evaluating the therapeutic effect of certain antihypertensive agents, their effect on glucose control and insulin sensitivity, and the progression of diabetic nephropathy are reviewed. Recommendations on the treatment of the patient with diabetes and hypertension are given. CONCLUSIONS: The treatment of the patient with diabetes mellitus and hypertension remains complex. Interventions in this patient population should not only decrease blood pressure, but also reduce the risk of both vascular and nonvascular complications. Data support the theory that by controlling a patient's hypertension, the incidence of albuminuria and the progression of diabetic nephropathy are slowed. Additionally, data are available to support the use of pharmacologic interventions in nonhypertensive patients with diabetes and proteinuria. Drug therapies that have produced reductions in proteinuria in this patient population include angiotension-converting enzyme inhibitors and nondihydropyridine calcium-channel antagonists. Additional information is needed to better differentiate the individual agents within each of the antihypertensive drug classes regarding their individual effects on the patient with diabetes and hypertension, specifically effects on diabetic nephropathy and its progression to endstage renal disease.

Adrenergic alpha-Antagonists↗