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Biomedical subjects

J R Wilson

Publications and source records attributed to J R Wilson.

At least 163 records · Page 9Linked to original sources
PubMed1988

One-month repeatability of emotional responses to alcohol.

Thirty-four subjects in the Colorado Alcohol Research on Twins and Adoptees (CARTA) were brought back between 30 to 60 days after their initial testing to be retested on all the CARTA procedures. As before, subjects were given a dose of ethanol (0.8 g/kg) calculated to bring their blood alcohol concentration (BAC) to near 0.10 g/dl. Additional doses were given at the end of each of the next 2 hr to maintain their BAC near peak for approximately 3 hr. During both testings, subjects' self-reports of their emotional responses and perceived intoxication following alcohol dosing were only minimally correlated with their alcohol metabolism parameters and reported average level of alcohol use. Repeatabilities (test-retest correlations) for subjects' self-reports of positive affect and of intoxication following alcohol dosing were consistently high, in contrast to earlier reports of minimal repeatabilities for alcohol metabolism and responses to alcohol on physiological, motor coordination, reaction time, and perceptual speed measures. Tester ratings of the subjects' levels of intoxication were also moderately stable between the two testings.

Adoption↗
PubMed1988

Effect of experimental heart failure on peripheral sympathetic vasoconstriction.

To investigate whether heart failure impairs peripheral sympathetic vasoconstriction, hindlimb vascular responses to lumbar chain stimulation (0.5-20 Hz) were studied in normal dogs and in dogs with chronic heart failure produced by rapid ventricular pacing. At lumbar chain stimulation rates of 0.5-3 Hz, hindlimb vascular responses were comparable in both groups. However, at stimulation rates of 5-20 Hz, vascular responses were significantly attenuated in the dogs with heart failure. Vascular responses to norepinephrine (0.1, 1, and 10 micrograms/min) were not altered. These findings suggest that chronic heart failure results in impaired sympathetic vasoconstriction, probably because of reduced neurotransmitter release. This abnormality may interfere with the capacity of the failing circulation to compensate for a low cardiac output and thereby intensify the severity of heart failure.

Animals↗
PubMed1988

Relationship of muscular fatigue to pH and diprotonated Pi in humans: a 31P-NMR study.

Seventeen normal subjects performed maximal wrist flexion exercise with continuous monitoring of forearm muscle pH and H2PO4-, measured with 31P nuclear magnetic resonance, and muscle fatigue, expressed as a percentage of decline in maximal developed force. Four minutes of exercise (flexion duration = 1 s) reduced maximal developed force from 100 to 74 +/- 9% and pH from 6.99 +/- 0.04 to 6.17 +/- 0.33 and increased H2PO4- to 927 +/- 401% of resting levels. In all subjects, linear relationships were noted between developed force and pH (r = 0.90 +/- 0.08) and between developed force and H2PO4- (r = -0.89 +/- 0.08). Doubling the contraction duration to 2 s produced more rapid changes in developed force, pH, and H2PO4- but no change in the relationship of force to pH and H2PO4-. Two minutes of submaximal exercise before maximal exercise significantly reduced pH and increased H2PO4-. During subsequent maximal exercise, the relationship between developed force and H2PO4- remained unchanged. In contrast, the relationship between developed force and pH was shifted leftward; muscle pH remained lower throughout maximal exercise, and developed force remained comparable to that noted during control exercise. These observations suggest that muscle fatigue during intense short-term exercise is primarily caused by an increase in intramuscular H2PO4- rather than by a decrease in intramuscular pH.

Adult↗
PubMed1988

Effect of T-2 toxin on brain biogenic monoamines in rats and chickens.

Two experiments were conducted to determine the effect of T-2 toxin on brain biogenic monoamines and their metabolites. Male rats (180 g) and cockerels (28 day, 300 g) were orally dosed with T-2 toxin at 2.5 mg kg-1 body weight. In the first experiment, whole brains were collected 2, 6, 12, 24 and 48 h postdosing and analyzed for monoamines by high performance liquid chromatography with electro-chemical detection. T-2 toxin did not influence whole brain concentrations of monoamines in either species. In the second experiment, brains were collected 24 h postdosing, dissected into five brain regions, and analyzed for monoamines. T-2 toxin treatment resulted in increased serotonin and 5-hydroxy-3-indoleacetic acid in all brain regions of the rat. However, this was not seen in poultry where T-2 toxin treatment resulted in an increase in 5-hydroxy-3-indoleacetic acid, no alteration in serotonin concentration and a decrease in regional norepinephrine and dopamine concentrations. These results suggest that T-2 toxin influences brain biogenic amine metabolism and that there is an intraspecies difference in the central effects of this mycotoxin.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Distribution, purification and characterization of rat intestinal UDPgalactose: N-acetylglucosaminyl(beta 1----4)galactosyltransferase.

Rat intestinal UDPgalactose: N-acetylglucosaminyl(beta 1----4)galactosyltransferase activity was studied as to its intestinal and villus-to-crypt distribution, and then purified and characterized. Rapid UDPgalactose hydrolysis was noted in the duodenum and jejunum; little to no breakdown was detected in the distal ileum, cecum and proximal colon. Product analysis suggested that UDPgalactose hydrolysis was due to nucleotide-sugar pyrophosphatase and galactose-1-phosphate phosphatase activities; ileum appeared to have little of the first activity and none of the latter. An aboral gradient of galactosyltransferase activity was noted, activity being 3-4-fold higher in the ileum, cecum and proximal colon. Total homogenate exogenous acceptor galactosyltransferase activities showed no villus-crypt differences but activity measured with intact isolated cells demonstrated higher activity with crypt cells; this was particularly evident in the ileum. Galactosyltransferase activity was purified from ileal-colonic mucosa. An over 4000-fold purification with 75 percent yield was achieved. Only one band of approx. 70-75 kDa was noted on sodium dodecyl sulfate polyacrylamide electrophoresis. As with other eukaryotic galactosyltransferase activities, there was an absolute requirement for Mn2+; the concentration required for half maximal activity was only 2.5 microM and higher concentrations did not inhibit. The Km for UDPgalactose was 30 microM.

Animals↗
PubMed1987

The distribution and partial characterization of UDPgalactose: N-acetylgalactosamine mucin galactosyltransferase activity from rat small intestine and its sensitivity to Zn2+.

UDPgalactose: N-acetylgalactosamine mucin galactosyltransferase activity of the rat intestine was studied and purified using asialo-ovine submaxillary mucin as the acceptor substrate and inhibitors to suppress UDPgalactose breakdown by pyrophosphatase activities particularly prevalent in the duodenal-jejunal regions. Despite adequate suppression of UDPgalactose breakdown, significant intestinal region differences of mucin galactosyltransferase activity were observed. Elevations of activity were observed in the duodenum and distal ileum of the small intestine and the cecum and proximal colon; these elevations in activity correspond to areas of increased mucin production. Similarly, mucin galactosyltransferase activity of duodenal cells isolated along a crypt-to-villus axis showed a moderate increase (67.7%) in activity associated with cells in the crypt region. Small intestine mucin galactosyltransferase activity was purified 800-fold using a series of ion exchange (DEAE-Sepharose), gel filtration (S-200 Sephacryl) and affinity chromatographic steps to isolate the mucin galactosyltransferase activity from a Triton X-100/Nonidet P-40 extract of homogenized cells obtained by scraping everted intestines. The partially purified enzyme showed two distinct protein bands of 81.5 and 50 kDa and a faint band at 53.3 kDa. Kinetic analysis gave an apparent Km of 152 microM for UDPgalactose. The enzyme showed optimal activity with Mn2+ (20 mM) and partial activities using a number of other divalent cations. Higher concentrations of Mn2+ were slightly inhibitory. Mucin galactosyltransferase activity was inhibited by more then 90% in the presence of Zn2+ (4 mM) and this inhibition could not be reversed by additional Mn2+. Addition of Zn2+ (4 mM) to assays containing Mn2+ (20 mM) did not cause appreciable UDPgalactose breakdown, as measured by high-voltage paper electrophoresis, suggesting that Zn2+ inhibition is not a result of pyrophosphatase activation. In addition, Zn2+ does not appear to activate a protease or glycosidase activity in the partially purified enzyme preparation which could hydrolyze the galactosylated product prior to isolation.

Galactosyltransferases↗
PubMed1987

Hypertension and obesity in rats with ventromedial-hypothalamic lesions and low salt intake.

The arterial hypertension that frequently coexists with ventromedial hypothalamic (VMH) lesion-induced obesity has been obtained in rats chronically sustained on diets of standard-to-high salt content. Since VMH lesions also compromise the renal circulation and enhance ingestion of salt-loaded diets, the resulting haemodynamic adjustments, including hypertension, have been interpreted as possibly being sodium-dependent. This notion implies that chronically restricting dietary salt would ameliorate the hypertension, whereas the persistence of hypertension under such a regiment would suggest the potential contribution of non-sodium-related factors. This study assessed whether chronic maintenance of a low-salt diet would buffer the hypertensive and haemodynamic consequences of obesity, accompanying electrolytic VMH lesions in male Wistar-Kyoto (WKY) rats, compared with sham-treated controls. Despite the low-salt diet, the results showed that VMH obesity was accompanied by hypertension, elevated plasma norepinephrine, and redistribution of blood flow away from the brain, kidney and splanchnic organs. The compatibility of these results with earlier studies permitting salt ingestion, is difficult to reconcile with the notion that VMH-hypertension is sodium-dependent. Instead, it suggests that the VMH obesity-hypertension syndrome may provide a useful model for clarifying the autonomic consequences of either augmented carbohydrate ingestion of hyper-insulinaemia.

Animals↗
PubMed1987

Influence of family alcoholism history on alcohol metabolism, sensitivity, and tolerance.

As part of the Colorado Alcohol Research on Twins and Adoptees (CARTA), 35 subjects who reported having an alcoholic parent or sibling [family alcoholism history positive (FHP)] were matched with 35 controls [family alcoholism history negative (FHN)]. All subjects were tested three times on a battery of physiological, motor, and cognitive performance tasks before the ingestion of alcohol, then were tested three more times over a 3-hr period during which their blood alcohol concentration (BAC) was brought up to and maintained at about 0.10 g/dl by an initial large dose of ethanol and subsequent topping doses. FHP subjects scored significantly lower than FHN subjects on the Raven's Progressive Matrices and on some of the cognitive tasks before alcohol ingestion. FHP and FHN subjects, however, did not significantly differ in absorption and clearance of alcohol or in sensitivity and acute tolerance scores calculated on the repeated measures. Contrary to expectations, FHP subjects perceived themselves as being more impaired by alcohol than FHN subjects, and there was little evidence to suggest that they were less sensitive to variations in BAC.

Adoption↗
PubMed1987

Experimental congestive heart failure produced by rapid ventricular pacing in the dog: cardiac effects.

Chronic rapid ventricular pacing in the dog reportedly produces a useful preparation of low-output heart failure. However, little information is available regarding cardiac changes in this preparation. Accordingly, we evaluated the effects of both short-term (3 weeks) and prolonged (2 months) rapid ventricular pacing on cardiac hemodynamics, mass, and chamber size. The effects of short-term pacing on left ventricular wall thickening, blood flow, and metabolism were also examined. Compared with 16 control dogs, dogs paced for either 3 weeks (n = 8) or 2 months (n = 13) exhibited reduced cardiac outputs (control 130 +/- 20 ml/min/kg, 3 week pacing 112 +/- 19 ml/min/kg, 2 month pacing 116 +/- 14 ml/min/kg) and elevated pulmonary wedge pressures (control 10 +/- 3 mm Hg, 3 week pacing 26 +/- 5 mm Hg, 2 month pacing 26 +/- 8 mm Hg) and right atrial pressures (control 4 +/- 1 mm Hg, 3 week pacing 13 +/- 3 mm Hg, 2 month pacing 9 +/- 3 mm Hg) (all p less than .01 vs control). At the postmortem examination, both groups of paced dogs also exhibited increased left ventricular volumes (control 13 +/- 6 ml, 3 week pacing 27 +/- 6 ml, 2 month pacing 26 +/- 8 ml), right ventricular volumes (control 13 +/- 5 ml, 3 week pacing 27 +/- 9, 2 month pacing 24 +/- 7 ml), and right ventricular mass (control 27 +/- 5 g, 3 week pacing 32 +/- 6 g, 2 month pacing 34 +/- 6 g) (all p less than .03 vs control) but had normal left ventricular mass. Three weeks of pacing also decreased percent left ventricular shortening (34 +/- 6% to 17 +/- 7%) associated with a disproportionate deterioration of posterior wall thickening (58 +/- 16% to 17 +/- 18%) (both p less than .01), as assessed by echocardiography. This left ventricular dysfunction was associated with no change in myocardial lactate extraction (prepacing 40 +/- 10%, 3 week pacing 36 +/- 10%), myocardial arteriovenous O2 difference, or myocardial histology, suggesting that it was not due to myocardial ischemia. These data indicate that rapid ventricular pacing in the dog produces a useful experimental preparation of low-output heart failure characterized by biventricular pump dysfunction, biventricular cardiac dilation, and nonischemic impairment of left ventricular contractility.

Animals↗
PubMed1987

Ethanol metabolism in men and women.

Data from the Colorado Alcohol Research on Twins and Adoptees project were analyzed to determine whether 63 women and 75 men differ on three measures of ethanol pharmacokinetics: absorption rate, peak blood alcohol level and elimination rate. The data on women were analyzed separately to investigate whether female hormones influenced the measures of ethanol metabolism by comparing groups tested at different phases of the menstrual cycle and a group who were taking oral contraceptives. Subjects were given 0.80 g of alcohol per kg of body weight diluted by 7 parts of carbonated water or a sugar- and caffeine-free soft drink. This dose was calculated to bring their blood alcohol level (BAL) to near 100 mg/dl. Additional doses were given at the end of each of the next 2 hr in an attempt to maintain BAL near peak for approximately 3 hr. An analysis of beta 60 values showed that women metabolized ethanol faster than men, regardless of phase of menstrual cycle or whether they were taking birth control pills. There was a small gender difference in peak BAL and no gender difference in time to peak BAL. It was also found that the peak BAL attained by subjects had a substantial effect on the beta 60. The effects of smoking, age, ponderal index and reported drinking habits on ethanol metabolism were also analyzed.

Adult↗
PubMed1987

One-month repeatability of alcohol metabolism, sensitivity and acute tolerance.

Subjects (N = 34) in the Colorado Alcohol Research on Twins and Adoptees (CARTA) were brought back between 30 and 60 days after their initial testing to be retested on all the CARTA procedures. As before, subjects were given a dose of alcohol (.8 g/kg of body weight) calculated to bring their blood alcohol level (BAL) to near 100 mg/dl. Additional doses were given at the end of each of the next 2 hours to maintain their BAL near peak for approximately 3 hours. Repeatability (test-retest correlation) for alcohol clearance rate was near 0, with repeatabilities between .40 and .55 for peak BAL, time-to-peak BAL, average session BAL and relative volume of alcohol distribution. Repeatabilities of prealcohol baseline scores were generally high (median, .71) for the CARTA battery of physiological, motor coordination, perceptual speed and reaction time measures, but were only low to moderate for sensitivity scores (median, .27) and acute tolerance scores (median, .25) calculated on these measures. There was some evidence that repeatabilities for alcohol metabolism, sensitivity and acute tolerance were lower for women than for men.

Adoption↗
PubMed1987

Use of antiarrhythmic drugs in patients with heart failure: clinical efficacy, hemodynamic results, and relation to survival.

Patients with chronic heart failure have a high incidence of both complex ventricular arrhythmias and sudden death. Therefore administration of antiarrhythmic agents to these patients to prevent lethal ventricular arrhythmias is theoretically appealing. However, at present there are no prospective randomized studies supporting this approach, whereas retrospective studies have yielded conflicting results. Moreover, the use of antiarrhythmic agents in patients with heart failure has two potentially serious side effects: worsening of ventricular pump function and exacerbation of ventricular arrhythmias. Such information suggests that the use of antiarrhythmic agents to treat patients with heart failure who do not have symptomatic ventricular arrhythmias is currently not indicated.

Anti-Arrhythmia Agents↗
PubMed1987

Exercise and the failing heart.

In summary, patients with chronic heart failure are frequently limited during exercise, even if they are asymptomatic at rest. Maximal exercise testing, preferably coupled with respiratory gas analysis, provides an objective method of assessing this functional limitation. Exercise testing also offers an objective method of noninvasively evaluating circulatory function in patients and, potentially, of monitoring responses to therapeutic interventions.

Blood Circulation↗
PubMed1987

Abnormal development of the axial length of aphakic monkey eyes.

Neonatal cataract surgery is becoming more common because irreversible amblyopia occurs if an eye receives inadequate inputs during an early sensitive period of visual development. To model conditions for treating congenital monocular cataracts in humans, we have reared rhesus monkeys which underwent unilateral lensectomy as neonates. Post-surgical A-scan ultrasonography at 8-26 months revealed that the axial length of the aphakic eye in these monkeys was shorter when compared to that of the unoperated eye. This finding has important implications for the long-term clinical management of lensectomized infants in order to achieve good vision in the aphakic eye.

Animals↗
PubMed1986

Use of maximal bicycle exercise testing with respiratory gas analysis to assess exercise performance in patients with congestive heart failure secondary to coronary artery disease or to idiopathic dilated cardiomyopathy.

Analysis of respiratory gases during maximal treadmill exercise testing has been used in patients with congestive heart failure (CHF) to detect the lactate threshold, presumed to reflect the onset of skeletal muscle underperfusion, and maximal oxygen consumption (VO2), the point at which VO2 plateaus with increasing work due to exhaustion of peripheral oxygen delivery capacity. To determine if this approach is also useful during maximal bicycle exercise testing, ventilatory, hemodynamic and systemic lactate responses to bicycle exercise were measured in 48 patients with CHF. Ventilatory responses also were assessed in 12 normal subjects. Exercise increased VO2 to 24.8 +/- 3.9 ml/min/kg in normal subjects and 13.9 +/- 3.7 ml/min/kg in patients with CHF (p less than 0.001). In all but 1 patient the VO2 increment over the last 3 minutes of exercise was comparable to that in normal subjects exercising over identical work times, suggesting that maximal VO2 was not achieved. Moreover, in patients who exercised for less than 6 minutes, a ventilatory lactate threshold could not be identified. In the 33 patients who exercised longer, a ventilatory lactate threshold was identified in 31 and correlated well (r = 0.81) with blood lactate threshold, as defined by the VO2 at which lactate increased 5 mg/dl over rest levels. However, the 95% confidence limit for predicting blood lactate threshold from ventilatory data was +/- 200 ml/min, a large range relative to the measured ventilatory threshold (570 +/- 132 ml/min). These data suggest that in patients with CHF, respiratory gas analysis during maximal bicycle exercise cannot be used to measure maximal VO2 and provides only a general index of blood lactate behavior.

Cardiac Output↗
PubMed1986

Synaptic connections of relay and local circuit neurons in the monkey's dorsal lateral geniculate nucleus.

The synaptic inputs to a single neuron's dendritic tree can be analyzed using electronmicroscopic reconstructions after intracellular injections of horseradish peroxidase. In the monkey's dorsal lateral geniculate nucleus, the proximal dendrites of magnocellular and parvocellular relay cells received retinal synapses and inhibitory synapses, while the intermediate and distal dendrites received cortical synapses. A local circuit neuron had both similar synaptic inputs and similar physiology to parvocellular relay neurons, but additionally had presynaptic dendrites and no axon. These results provide a wiring diagram for the neuronal types in this nucleus.

Animals↗
PubMed1986

Exercise ventilation and pulmonary artery wedge pressure in chronic stable congestive heart failure.

In patients with chronic heart failure (CHF), physical exertion frequently is associated with higher than normal ventilatory levels and dyspnea. To determine the prevalence of such excessive ventilatory responses in CHF and whether this excessive ventilation is a result of acute increases in intrapulmonary pressure during exercise, minute ventilation (VE) and pulmonary artery (PA) wedge pressure were measured during maximal bicycle exercise in 38 patients with chronic CHF. It was then determined whether reducing the PA wedge pressure during exercise with prazosin (9 patients) or dobutamine (6 patients) reduced ventilatory levels toward normal. To compare ventilation between patients, VE was correlated with minute carbon dioxide production (VCO2) (r greater than or equal to 0.90); the calculated VE at a VCO2 of 1 liter/min (VE-CO2) was derived from this relation and used as a normalized index of ventilation. During exercise, VE-CO2 ranged from 27 to 71 liters/min, exceeding the normal range in 37 of 38 patients (normal 33 liters/min or less). VE-CO2 did not correlate with peak exercise PA wedge pressure and correlated only weakly with PA wedge pressure at rest (r = 0.48). Acute reduction in the PA wedge pressure during exercise with prazosin or dobutamine did not significantly reduce VE-CO2. These data suggest that ventilatory levels are frequently excessive during exercise in patients with CHF and therefore may provide a useful, objective index of their altered pulmonary function. In addition, our data suggest that this excessive ventilation is not a result of acute changes in intrapulmonary pressure during exercise.

Cardiac Output↗