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Biomedical subjects

J R Wilson

Publications and source records attributed to J R Wilson.

At least 127 records · Page 7Linked to original sources
PubMed1991

Beta-adrenergic receptor-G protein-adenylate cyclase complex in experimental canine congestive heart failure produced by rapid ventricular pacing.

Changes in the beta-adrenergic receptor-G protein-adenylate cyclase complex were investigated in an experimental canine model of low-output heart failure produced by chronic rapid ventricular pacing. The contractile response occurring after exposure to the beta-adrenergic agonist dobutamine, measured as peak left ventricular + dP/dt, was decreased after 3 weeks of pacing. To further characterize the diminished functional responsiveness to beta-adrenergic receptor stimulation, beta-adrenergic receptor-adenylate cyclase coupling was investigated using membranes prepared from both control and paced animals. The density of beta-adrenergic receptors was decreased by 40% with a selective downregulation of the beta 1-subtype. The affinity of the receptor for the antagonist radioligand [125I]iodocyanopindolol remained unchanged. A defect in coupling was suggested by a decreased ability of isoproterenol, fluoride, and forskolin to stimulate adenylate cyclase in membranes prepared from failing hearts. Determination of the levels of Gi alpha (the alpha-subunit of Gi) by immunoblotting and pertussis toxin labeling revealed modest increases of approximately 30%. Furthermore, Mn2+ and purified Gs failed to stimulate adenylate cyclase in membranes prepared from failing hearts, indicating an impairment in the catalytic moiety of adenylate cyclase itself or in the ability of adenylate cyclase to couple to Gs. In contrast, complementation assay did not reveal differences in the functional activity of Gs alpha (the alpha-subunit of Gs). Taken together, these data demonstrate a selective decrease in the beta 1-subtype of adrenergic receptors and an increase in a 40-kd G1-like protein in the failing heart. Similar changes have been described in human idiopathic dilated cardiomyopathy. In addition to these changes, we identified a possible defect at the level of the catalytic subunit of adenylate cyclase.

Adenylate Cyclase Toxin↗
PubMed1991

Anticipated and subjective sensitivities to alcohol.

The development and maintenance of alcohol use patterns may depend, in part, on differences between how an individual anticipates he will respond to alcohol and how he appears to others when he is drinking. Such differences may introduce bias in decisions regarding which activities are safe while under the influence of an intoxicating amount of alcohol. This study of 387 participants of the Colorado Alcohol Research on Twins and Adoptees project examined the interrelationships of anticipated, subjective and observer-judged sensitivity to a blood alcohol concentrations of about 0.1 g/dl (approximated by breath alcohol concentration). Differences among the sensitivity measures were dependent upon recent alcohol drinking history and individual differences in actual sensitivity (as observer-rated). The results were consistent with hypotheses that people with little drinking experience may overestimate how intoxicated they will be, that heavier drinkers may develop chronic tolerance to the intoxicating effects and that denial may play a role in both subjective and anticipated sensitivity.

Adult↗
PubMed1990

Effect of dobutamine on skeletal muscle metabolism in patients with congestive heart failure.

Dobutamine is known to increase leg blood flow during exercise in patients with heart failure. However, it is uncertain whether the increased flow is delivered to working skeletal muscle. In 7 patients with heart failure, the effects of dobutamine were examined on calf phosphorus-31 magnetic resonance spectroscopy (MRS) spectra and femoral vein blood flow during rest and upright plantar flexion. During upright plantar flexion every 3 seconds, dobutamine increased femoral venous blood flow (control 1.7 +/- 0.1; dobutamine 2.1 +/- 1.0 liters/min; p less than 0.05) and increased femoral venous O2 saturation (control 24 +/- 5%; dobutamine 31 +/- 2%; p less than 0.05), indicating improved total leg blood flow. However, dobutamine did not change the slope of the relation between systemic VO2 and the calf inorganic phosphate to phosphocreatine relation (control 0.0054 +/- 0.0039; dobutamine 0.0056 +/- 0.0032; difference not significant) and did not change muscle pH, suggesting no improvement in blood flow to active skeletal muscle. These findings suggest that dobutamine does not improve oxygen delivery to working skeletal muscle in patients with heart failure, despite its ability to increase cardiac output and limb blood flow.

Dobutamine↗
PubMed1990

Arterial baroreceptor control of peripheral vascular resistance in experimental heart failure.

Heart failure is known to impair arterial baroreceptor control of heart rate. To determine if baroreceptor control of peripheral vascular resistance is also impaired, heart rate and hind limb vascular responses to phenylephrine and nitroglycerin administration were compared in control dogs and in dogs with heart failure produced by chronic rapid ventricular pacing. Baroreflex control of the heart rate was depressed in the dogs with heart failure, as evidenced by a reduced slope of the blood pressure-to-heart rate relationship (controls: -2.5 +/- 0.3 beats/mm Hg versus heart failure: -1.5 +/- 0.2 beats/mm Hg [(p less than 0.04)]). Arterial blood pressure in the dogs with heart failure was also reduced (controls: 90 +/- 3 mm Hg versus heart failure: 75 +/- 3 mm Hg [(p less than 0.01)]). Nevertheless, dogs with heart failure exhibited normal slopes of the blood pressure versus hind limb vascular resistance relationship (controls: -2.4 +/- 0.4 units/mm Hg versus heart failure: -2.9 +/- 0.5 units/mm Hg [(p = NS)]), consistent with preserved baroreflex control of the peripheral vasculature. These data suggest that heart failure impairs arterial baroreflex control of heart rate and lowers the baroreflex pressure operating range but does not alter baroreflex control of peripheral resistance.

Animals↗
PubMed1990

Rat small intestinal laminin-binding proteins.

Mucosal intestinal cells migrate and differentiate simultaneously as they move out of the crypts to their functional site along the villus. Interactions between the enterocyte basal membrane domain and the extracellular intestinal basement membrane (IBM) have been suggested to be essential to both cell migration and differentiation. The IBM is composed primarily of collagen IV, laminin, fibronectin and heparan sulfate proteoglycans. It is likely that enterocytes possess receptors to various IBM components as they adhere to this IBM, an essential scaffold for villus structural integrity. In addition, the enterocyte must have mechanisms of altering this adherence to IBM as the cell moves up the villus and is eventually expelled into the lumen. To understand these processes, enterocyte membrane proteins involved in cell to IBM adhesion need to be defined. In the present study, laminin-binding proteins have been identified in enterocyte membranes. These binding proteins were isolated and purified. Antibodies raised against these binding proteins were used to further characterize these enterocyte membrane proteins. A major antigen at 67-69 kD was detected from both villus and crypt cells, although upper crypt cell membranes appeared to have more. Other antigens at 41, 43, 52, 100 and 130 kD were also detected. Immunofluorescent studies showed antigens present in the basal domain of the crypt enterocyte. These laminin-binding proteins may prove important as inducers of differentiation and in the dynamic alterations required for cell movement.

Animals↗
PubMed1990

The mechanism of extertional fatigue in heart failure.

The mechanism of exertional fatigue in heart failure appears to be considerably more complex than was originally thought. Although it still seems likely that muscle underperfusion is the major culprit, the possibility that skeletal muscle changes contribute to the fatigue suggests that several new therapeutic modalities may improve exercise capacity in heart failure. If muscle atrophy due to de-conditioning or malnutrition is found to contribute to fatigue, exercise capacity in heart failure could be improved, at least in part, by exercise training or nutritional supplementation. Alternatively, agents such as anabolic steroids or growth hormone could be used to stimulate muscle hypertrophy and, thereby, help to improve the fatigue. Heart failure is a common disorder, affecting over three million Americans and many more people throughout the world. One of the most disabling problems experienced by these patients is exertional fatigue. Patients report that they are easily fatigued during normal daily activity. During maximal exercise testing, patients usually terminate exercise early due to fatigue of the legs associated with an early increase in the concentration of lactate in the blood. Traditionally, such exertional fatigue has been attributed to skeletal muscle underperfusion. Over the past five years, however, there has been increasing evidence that heart failure is associated with intrinsic skeletal muscle changes which may also contribute to the exertional fatigue. Nuclear magnetic resonance studies using 31P have demonstrated abnormal skeletal muscle metabolic responses to exercise that do not appear to be due to muscle under-perfusion. Skeletal muscle biopsy studies have demonstrated a variety of changes in patients. Anthropometric studies suggest that a generalized loss of muscle mass may occur in heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise↗
PubMed1989

Visual fields of monocularly deprived macaque monkeys.

The effects of postnatal monocular deprivation have been studied in macaque monkeys using behavioral perimetry field testing. The types of deprivation were: (1) early eyelid suture at 22-26 days after birth and then reverse suture at 10-13 months postnatally, (2) late eyelid suture beginning at 3 or 5 months postnatally and continued for 18 months, and (3) long-term occlusion by contact lenses. Response levels were normal for group 1 monkeys with some reduction in visual field extent. A reduced response level but no change in visual field extent was observed for the deprived eyes of group 2 monkeys. One monkey from group 3 that wore an occluder lens from birth to 19 months postnatally had no responses in any part of the visual field. Two other monkeys of group 3, whose occlusion started at 9 or 12 days of age and lasted for 2 years, had no responses to stimuli presented to the previously occluded eyes in their nasal visual fields and had reduced levels of response to stimuli presented in their temporal fields. The results indicate that the effects of monocular deprivation on macaque monkeys are affected by the start, length and type of deprivation. Some of these results are also consistent with a model of binocular competition in which the magnitude of the competition declines along a nasal-to-temporal gradient of visual field eccentricity. However, a mechanism that is independent of binocular competition is needed to account for the loss of responses to stimuli presented in the monocular visual segment.

Animals↗
PubMed1989

Characterization of lymphocyte beta-adrenergic receptors at rest and during exercise in ambulatory patients with chronic congestive heart failure.

To investigate beta-adrenergic receptor dysfunction in congestive heart failure (CHF), the density of lymphocyte beta receptors and adenylate cyclase activity was measured at rest and at peak exercise in 30 patients with CHF and 7 age-matched control subjects. At rest, patients with CHF had reduced beta-receptor density (normals 33 +/- 2; CHF 21 +/- 2 fmol/mg protein; p less than 0.01) and isoproterenol-stimulated adenylate cyclase activity (normals 50 +/- 9; CHF 28 +/- 4 pmol/mg protein/min; p less than 0.05). Sodium fluoride-stimulated adenylate cyclase activity was also reduced (normals 98 +/- 17; CHF 48 +/- 12 pmol/mg protein/min; p less than 0.01). In the patients with CHF, there was no significant correlation between receptor density and peak exercise VO2, ejection fraction or resting plasma catecholamines. In the normal subjects, maximal exercise increased beta-receptor density by 100% (rest 33 +/- 2; exercise 67 +/- 7 fmol/mg protein) and isoproterenol-stimulated adenylate cyclase activity by 66% (rest 50 +/- 9; exercise 83 +/- 18 pmol/mg protein/min (both p less than 0.01]. In contrast, patients with CHF exhibited only a 58% increase in beta-receptor density (rest 20 +/- 3; exercise 32 +/- 6 fmol/mg protein; p less than 0.01) and no significant change in isoproterenol-stimulated adenylate cyclase activity (rest 27 +/- 5; exercise 24 +/- 5 pmol/mg protein/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1989

Behavioral and reproductive differences in mice as a function of inbreeding.

Twenty brother-sister pairs of mice were randomly selected from a genetically heterogeneous population of mice to begin a schedule of inbreeding that lasted for six generations (F = 0 to F = .732). We examined a number of indices of reproductive behavior and found that all declined as a function of inbreeding. Specifically, there was a consistent decline in the number of fertile matings, in the number of offspring that survived to weaning, and in the weight of the pups at the time of weaning (21 days of age). We also examined a number of behaviors with the following results: there was a systematic increase in the number of trials required to learn an active avoidance task and a consistent decrease in the number of trials required to extinguish this habit. We observed a statistically significant difference in the retention of a passive avoidance habit, but these results were quite variable and not consistent across generations of inbreeding. Finally, we observed that inbreeding had little effect on measures of locomotor behavior.

Animals↗
PubMed1989

Goldblatt hypertension and operant thermoregulation in shaved, sialoadenectomized rats.

The thermobehavioral consequences of angiotensinogenic two-kidney (2K) and sodium-volume dependent one-kidney (1K) forms of Goldblatt (one-clip) renovascular hypertension were assessed in shaved, sialoadenectomized rats. The 2K group (n = 8) underwent unilateral renal artery stenosis with the contralateral kidney left intact; whereas the Sham-Operation (Sham-Op) Control group (n = 7) received only a laparotomy. The 1K group (n = 8) underwent unilateral renal artery stenosis with contralateral nephrectomy, and the Uninephrectomy Control group (n = 6) was only unilaterally nephrectomized. Shaping and testing was conducted in a convective thermal controller that permitted the experimenters to control, through continuously reinforced bar-pressing, the ambient temperature during exposure to warm (37 degrees C) or cold (17 degrees C) temperatures. Testing at each temperature occurred over two 6-hr sessions with an interpolated 48-hr rest period. Both 2K and 1K hypertensive rats exhibited longer durations of heat escape than their appropriate normotensive controls across both testing sessions. No differences were detected in response frequency, duration of cold escape responding, or body temperature. The results suggest that either the increased vascular resistance or the neuroendocrine-sympathetic disorder linked to the pathogenesis of Goldblatt renovascular hypertension may promote heat retention or lower heat tolerance.

Animals↗
PubMed1989

Effects of central and peripheral neuropeptide Y on sodium and water excretion in the rat.

Neuropeptide Y (NPY) is widely distributed throughout the central nervous system and in several sympathetically innervated tissues, including the kidney. Although many central and peripheral acting endogenous compounds alter renal function, the role of NPY is unknown. Accordingly, we examined the effects of intracerebroventricular (ICV) or intrarenal administration of NPY on sodium and water excretion in the barbiturate anesthetized rat. Sprague-Dawley rats were uninephrectomized 10 days prior to testing and, in rats undergoing ICV administration, cannulae were implanted 3 days prior to testing. For testing, rats were anesthetized (Nembutal) and the jugular vein, renal artery and ureter catheterized. The results showed that the intrarenal infusion of NPY at 1 microgram/kg/min increased sodium and water excretion relative to the saline control group without altering blood pressure or creatinine clearance. Similarly, ICV administration of NPY at 10 micrograms in a 5 microliters volume increased the excretion of sodium and water without altering blood pressure as compared to the artificial CSF group. These findings suggest that both central and peripheral NPY may contribute to the regulation of sodium and water excretion in the rat.

Animals↗
PubMed1989

Quantifying uncertainty in medical decisions.

Effective handling of uncertainty is one of the central problems in medical decision making. The sources and effects of uncertainty in medical decision making are examined and some new quantitative approaches for solving the associated problems are outlined. To handle uncertainty in the branching probabilities and node utilities for probability trees representing alternative treatment strategies, a public domain software package that can be used for the construction, analysis and comparison of probability trees with random parameters was developed. To facilitate specification of the random variables that arise in medical decision making problems, public domain software packages for both data-driven and subjective estimation of probability densities from the Johnson translation system of distributions have also been developed. For the analysis of complex problems that cannot be adequately represented by probability trees or by simple stochastic processes such as Markov chains, network simulation approaches that are oriented toward the sequence of activities seen by individual patients in the course of treatment are described.

Computer Simulation↗
PubMed1989

Clinical pulmonary function tests as predictors of work performance during respirator wear.

The Occupational Safety and Health Administration (OSHA) mandate requiring medical information for respirator users provides the physician with little or no guidance as to what objective criteria may be valuable in assessing the worker's ability to use a respirator safely. Therefore, the purpose of this study is to use the results of clinical pulmonary function testing to predict performance time on maximal- and endurance-type exercise tests. Respirator mask wear reduced clinical pulmonary function measures from 7%-15% from mouthpiece controls. The resistances of the mask reduced forced vital capacity by an average of 11.6% (0.65 L); forced expiratory volume in 1 sec by 7.3% (0.33 L); and maximum voluntary ventilation in 15 sec by 7.4% (12.4 L/min). Stepwise linear regression analysis was used to determine the clinical pulmonary function measures that were the best predictors of work performance. The MVV.25 with the respirator was determined to be the best predictor of maximal exercise performance both with and without the respirator. The difference in peak inspired flow with and without the respirator was the best predictor of performance time with the respirator during the endurance walk to exhaustion. Recommendations are made to the physician for procedures for determining a worker's pulmonary capacity and calculating the effect of the respirator in reducing that capacity. This information then will allow the physician to determine safe levels of ventilation for a particular work task.

Female↗
PubMed1989

Effects of pressure-demand respirator wear on physiological and perceptual variables during progressive exercise to maximal levels.

Current regulations governing the certification of respiratory protective devices are based on data published in the early 1950s. The limited data base of this early work and documented increases in the average height of the population underscore the need for additional information concerning the parameters of certification. In the present study, a protocol using an inclined treadmill (0.5% grade every 12 sec) was used to test a heterogeneous population (n = 38). Through submaximal up to and including maximal exercise levels with and without respirator wear, maximal oxygen uptake (VO2max) was significantly greater (p less than 0.01) with the respirator (44.11 +/- 1.3 mL/kg.min) than without the respirator (42.18 +/- 1.4 mL/kg.min) while maximal ventilation volumes (VEmax) were not significantly different (with = 118.7 +/- 4 L/min; without 119.6 +/- 5 L/min). While peak inspired flows (PFI) with the respirator (268 +/- 7 L/min) were less than without the respirator (281 +/- 9 L/min), p greater than 0.05, the lower peak expired flow (PFE) with the respirator (289 +/- 12 L/min) than without the respirator (324 +/- 13 L/min), p less than 0.01, indicated a significant blunting effect of the respiratory flows by the expired resistance during exercise to maximal levels. Peak inspired pressures (PPi) with and without the respirator were not significantly different (p greater than 0.05). The negative values obtained within the facepiece of the respirator (-7.65 +/- 0.8 cmH2O), however, indicate that the positive pressure within the facepiece was lost, and respiratory protection may be compromised. Peak expired pressure with the respirator (13.05 +/- 0.7 cmH2O) was significantly greater than without the respirator (10.7 +/- 0.5 cmH2O) indicating that, despite a lower PFE, greater force was required to overcome the resistances of the respirator on expiration. The dyspnea index, an index of physiological effort; suggests that the subjects were working at a higher percentage of their respiratory reserve with the respirator (p less than 0.05) than without. Perceptually, subjects also felt that breathing with the respirator was more difficult (p less than 0.05). The maximum heart rate and the ratings of perceived exertion were not significantly different between the two tests at maximal exercise levels. Maximum oxygen uptake was considered reached when subjects attained a respiratory exchange ratio of at least 1.15, when a heart rate response at or greater than age-predicted maximum was achieved, when ratings of perceived exertion indicated exhaustion, and/or when the measure of VO2 had plateaued during the final minute of exercise.(ABSTRACT TRUNCATED AT 400 WORDS)

Equipment Design↗
PubMed1989

Alterations in physiological and perceptual variables during exhaustive endurance work while wearing a pressure-demand respirator.

The purpose of this investigation was to describe the time course of changes in physiological and perceptual variables during exhaustive endurance work with and without an air-supplied, full-facepiece, pressure-demand respirator. Thirty-eight healthy subjects (24 to 51 years of age) volunteered for this study. Treadmill speed was set at 5.5 kph (3.4 mph) and elevation was set at a level calculated to elicit 70% of a previously determined maximal aerobic capacity (VO2max). Subjects continued at this rate to exhaustion. Despite a constant work rate, VO2 and %VO2max increased during exercise and were significantly greater with the respirator (34.4 +/- 1.1 mL/kg.min; 84% VO2max) than without the respirator (31.9 +/- 1.1 mL/kg.min; 76% VO2max) at the "final" measurement point prior to termination of exercise by each subject. The final values for ventilation volume (VE) also were significantly greater with the respirator (89.2 +/- 3.4 L/min) than without (73.4 +/- 3.7 L/min). At the conclusion of the endurance walk, dyspnea index (VE/MMV.25) remained well below maximal values (with = 58.6 +/- 2%; without = 44.6 +/- 2%; p less than 0.001). Also, at the final period, no significant differences occurred in the subjects' perceptual ratings of work of breathing, yet work performance time was significantly reduced (p less than 0.0001) from 69.1 +/- 4.4 min (without) to 55.6 +/- 3.8 min (with). A significantly greater swing in peak pressure (maximum pressure measured within the facepiece of respirator), however, from inspired (PPi) to expired (PPe) occurred with the respirator (13.42 cmH2O) than without the respirator (9.25 cmH2O).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

LS X SS recombinant inbred strains of mice: initial characterization.

In order to assess the genetic correlates of differences in ethanol-induced anesthesia, a set of 27 recombinant inbred (RI) strains was derived from an initial cross of the "long-sleep" (LS) and "short-sleep" (SS) selected lines of mice. In generations F24 and F25, samples of 534 and 580 mice from the LSXSS RI strains were tested for fall time, sleep time, and blood ethanol at awakening subsequent to intraperitoneal injection of a 4.1-g/kg body weight dose of ethanol. Approximately 2 weeks later, mice from F24 were also tested for body temperature lowering and blood-ethanol elimination rate (beta 60). Differences among the average ethanol-induced sleep-time scores of the RI strains are large (ranging from 36 to 171 min) and account for over 50% of the observed variance. Effects due to generation, sex, litters within strains, and the interaction between strain and generation are also significant, but account for relatively small proportions of the total variance. Quantitative genetic analyses of these data suggest that differences in sleep-time scores are polygenic; however, allelic differences at the albino (c) locus may have a pleiotropic effect. Genetic correlations between sleep time and blood ethanol at awakening (-0.79) and between body temperature 60 min after injection and beta 60 (+0.48) are significant. Because differences among the LSXSS RI strains are large and highly reliable, they should be valuable animal models for testing more searching hypotheses about the etiology of individual differences in ethanol-induced anesthesia.

Animals↗
PubMed1989

Effect of exercise duration on density and coupling of beta-adrenergic receptors on human mononuclear cells.

The effect of maximal exercise on lymphocyte beta-adrenergic receptors was examined in 26 normal subjects. Exercise increased O2 consumption (Vo2) from 5 +/- 1 to 50 +/- 4 ml.min-1.kg-1, plasma norepinephrine level from 188 +/- 28 to 2,682 +/- 160 pg/ml, and plasma epinephrine level from 94 +/- 72 to 857 +/- 180 pg/ml. The density of beta-adrenergic receptors on lymphocytes obtained at rest was 31 +/- 3.7 fmol/mg protein; exercise increased the density of receptors by 86 +/- 33% (range 0-257%) to 58.3 +/- 1.5 fmol/mg protein but did not alter the affinity of the receptor for [125I]iodopindolol or the coupling of the receptor to the guanine nucleotide-binding regulatory protein. The density of beta-adrenergic receptors increased progressively throughout exercise and paralleled the increase in heart rate. The magnitude of the change in the density of beta-adrenergic receptors did not correlate with the magnitude of the increase in heart rate, Vo2, or plasma levels of catecholamines. The density of receptors was still elevated 15 min after completion of exercise but fell below base line 1 h after peak exercise to 18.2 +/- 6.7 fmol/mg protein (P less than 0.05 vs. base-line levels). These results demonstrate that exhaustive exercise results in a progressive increase in the number of beta-adrenergic receptors on lymphocyte membranes, followed by a reduction in the density of receptors during the recovery phase of exercise. Despite a significant increase in the level of plasma catecholamines, the receptor remains coupled to the guanine nucleotide-binding regulatory protein.

Adult↗