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Biomedical subjects

T A Wilson

Publications and source records attributed to T A Wilson.

At least 91 records · Page 5Linked to original sources

Variability of parenchymal expansion measured by computed tomography.

Computed tomography scans of isolated dog lung lobes at different lobe volumes were used to determine the variability of parenchymal tissue density and the variability of parenchymal volume changes on the scale of a voxel, a cube 1.5 mm on a side. The variability of tissue density increased with decreasing lobe volume. The variability of tissue density of neighboring voxels was positively correlated; the spatial correlation decreased exponentially with distance with an exponential scale of 0.3 cm. The ratio of the volume of the parenchyma within a voxel to its volume at total lobe capacity was calculated from the tissue density data at two lobe volumes. At a lobe volume of 40% total lobe capacity, the local fractional volumes were 0.42 +/- 0.12. The variability of ventilation that corresponds to this variability of fractional volume is large enough to explain the inefficiency of mixing in the isolated lobe and the slope of the alveolar plateau of nitrogen concentration in the expirate after a breath of oxygen. These results are consistent with data reported earlier on the variability of parenchymal volumes at a scale of 1-10 cm3.

Animals↗

Atrial antinatriuretic factor in the developing Dahl hypertensive rat.

In order to determine the developmental pattern of atrial concentrations of atrial natriuretic factor (ANF) in the Dahl hypertension-prone rat, atrial ANF concentrations were measured in inbred hypertension-prone (S/JR) and hypertension-resistant (R/JR) Dahl rats at 5, 15, 25, and 51 days of age. In both strains, atrial ANF concentrations peaked at 15 days of age. Atrial ANF concentrations did not differ between the two strains from 5 to 25 days of age. However, by 51 days of age, atrial ANF concentrations in the S/JR rat were significantly greater than those of the R/JR rat. Combining these data with developmental patterns of plasma renin activity in S/JR rats suggests the possibility that the S/JR rat may become intravascularly volume-expanded between 25 and 51 days of age. This volume expansion may contribute to the etiology of hypertension in this model of essential hypertension.

Animals↗

Ontogeny of blood pressure in the inbred Dahl hypertension-sensitive and -resistant rat.

The inbred S/JR rat is characterized by a genetic predisposition to NaCl-induced hypertension. Although mature S/JR but not R/JR rats develop hypertension when fed a high NaCl-containing diet, this effect has not been examined during early neonatal development. S/JR and R/JR dams were maintained on 0.15% (w/w) or 8% (w/w) NaCl diets throughout gestation and lactation. Measurements of mean abdominal aortic blood pressure (MAP) were obtained in anesthetized offspring at 5, 15, and 25 days of age. This was greater in neonatal S/JR rats than R/JR rats at 5, 15, and 25 days of age. A hypertensinogenic effect of 8% NaCl was seen in R/JR at 5 and 15 days. The results indicate that the ontogeny of MAP can be influenced by pre- and postnatal dietary NaCl. More importantly, elevated MAP in the S/JR strain is a distinguishing characteristic evident throughout the neonatal period of development.

Animals↗

Mechanics of compartmental models of the chest wall.

Standard methods for describing the mechanical properties of a linear elastic system are applied to the two- and three-compartment models of the chest wall. The compliance matrix and the experiments required to determine the entries in this matrix and thereby to describe the mechanical properties of the relaxed chest wall are described. The effective forces exerted by external loads and muscle tension are defined. The formal theory is used to identify relations among variables. From the definition of effective force, it follows that the ratio of the forces exerted by the diaphragm on the rib cage and abdomen is the same as the ratio of the dependence of diaphragm length on rib cage and abdominal volumes. As an example of relations among variables that follow from the symmetry of the compliance matrix, it is shown that the change of gastric pressure caused by raising pleural pressure is related to the change in lung volume caused by changing stomach volume.

Abdomen↗

Coupling between rib cage and abdominal compartments of the relaxed chest wall.

The volume displacements of the rib cage and abdomen of relaxed seated subjects were measured as functions of pleural pressure with the chest wall expanded by airway pressure and with the chest wall distorted by an external force applied to the rib cage. From the measured displacements for the two independent loads, the three compliances that describe the mechanical properties of the relaxed chest wall modeled as a linear elastic system with two degrees of freedom were obtained. The cross compliance that describes the coupling between the rib cage and abdomen was found to be small and positive, 0.01-0.02 1/cmH2O. The displacement of the rib cage by the external force was consistent with the displacement predicted by use of standard methods for calculating the mechanical advantage of the force.

Abdomen↗

Parenchymal interdependence and airway response to methacholine in excised dog lobes.

The objective of this investigation was to determine the minimum transpulmonary pressure (PL) at which the forces of interdependence between the airways and the lung parenchyma can prevent airway closure in response to maximal stimulation of the airways in excised canine lobes. We first present an analysis of the relationship between PL and the transmural pressure (Ptm) that airway smooth muscle must generate to close the airways. This analysis predicts that airway closure can occur at PL less than or equal to 10 cmH2O with maximal airway stimulation. We tested this prediction in eight excised canine lobes by nebulizing 50% methacholine into the airways while the lobe was held at constant PL values ranging from 25 to 5 cmH2O. Airway closure was assessed by comparing changes in alveolar pressure (measured by an alveolar capsule technique) and pressure at the airway opening during low-amplitude oscillations in lobar volume. Airway closure occurred in two of the eight lobes at PL = 10 cmH2O; in an additional five it occurred at PL = 7.5 cmH2O. We conclude that the forces of parenchymal interdependence per se are not sufficient to prevent airway closure at PL less than or equal to 7.5 cmH2O in excised canine lobes.

Airway Obstruction↗

Structural studies of mutants of the lysozyme of bacteriophage T4. The temperature-sensitive mutant protein Thr157----Ile.

To understand the roles of individual amino acids in the folding and stability of globular proteins, a systematic structural analysis of mutants of the lysozyme of bacteriophage T4 has been undertaken. The isolation, characterization, crystallographic refinement and structural analysis of a temperature-sensitive lysozyme in which threonine 157 is replaced by isoleucine is reported here. This mutation reduces the temperature of the midpoint of the reversible thermal denaturation transition by 11 deg.C at pH 2.0. Electron density maps showing differences between the wild-type and mutant X-ray crystal structures have obvious features corresponding to the substitution of threonine 157 by isoleucine. There is little difference electron density in the remainder of the molecule, indicating that the structural changes are localized to the site of the mutation. High-resolution crystallographic refinement of the mutant lysozyme structure confirms that it is very similar to wild-type lysozyme. The largest conformational differences are in the gamma-carbon of residue 157 and in the side-chain of Asp159, which shift 1.0 A and 1.1 A, respectively. In the wild-type enzyme, the gamma-hydroxyl group of Thr157 participates in a network of hydrogen bonds. Substitution of Thr157 with an isoleucine disrupts this set of hydrogen bonds. A water molecule bound in the vicinity of Thr155 partially restores the hydrogen bond network in the mutant structure, but the buried main-chain amide of Asp159 is not near a hydrogen bond acceptor. This unsatisfied hydrogen-bonding potential is the most obvious reason for the reduction in stability of the temperature-sensitive mutant protein.

Crystallography↗

Effect of variable parenchymal expansion on gas mixing.

Using implanted radiopaque markers, Hubmayr et al. (J. Appl. Physiol. 54: 1048-1056, 1983) and Olson et al. (J. Appl. Physiol. 57: 1710-1714, 1984) detected a variability in the volume changes of regions defined by the markers in intact and excised dog lungs, respectively. In dogs lying prone and in excised lobes, there is virtually no large-scale spatial organization of the variability. We interpret these data as evidence of an intrinsic heterogeneity of parenchymal expansion. The effect of variability of parenchymal expansion on gas mixing is calculated. From a statistical model, we infer that the variability of volume changes observed by Olson et al. is a result of an underlying variability with a larger magnitude at a smaller scale and that the variability at the smaller scale is large enough to explain the inefficiency of mixing observed in single-breath oxygen tests on excised dog lobes.

Animals↗

Geometry and respiratory displacement of human ribs.

The three-dimensional coordinates of points in the ribs of two supine relaxed males, holding their breath at functional residual capacity (FRC) and with their glottis closed at total lung capacity (TLC), were obtained from volumetric X-ray computed tomographical images. The orientation of planes that best fit the data for each rib at each lung volume and the circular arcs that fit the points in the planes of the ribs were determined, and average values of these geometrical parameters for ribs 3-7 are reported. The planes of the ribs at TLC can be described as displaced from the planes at FRC by a rotation about an axis that passes near the spine. The pump handle and bucket handle components of rotation are 11 and 13 degrees, respectively, for rib 3 and both decrease with increasing rib number to 7 and 10 degrees at rib 7. The angles between the axes of rotation and the midplane are approximately 35 degrees for all 5 ribs. The radii of the circular arcs fit to the data at TLC are slightly larger than those at FRC, and this suggests that there is a small component of rotation normal to the plane of the rib.

Adult↗

H-Y intermediate phenotype in male pseudohermaphroditism.

A child with ambiguous genitalia was born after an uncomplicated pregnancy. Laparotomy revealed intraabdominal hypoplastic testes containing normal appearing Leydig cells; germ cells were present in the left gonad, not in the right. The karyotype was 46,XY in blood leukocytes and in fibroblasts cultured from the gonads; there was no evidence of mosaicism. Endocrinologic study revealed no disorder of steroidogenesis. Androgen receptors were not studied. Serologic evaluation of blood leukocytes revealed the presence of H-Y antigen, but there are reasons to believe that less H-Y antigen was present in the cells of the patient than was present in corresponding cells from normal males. Gonadectomy and clitoral recession were performed at 3 weeks of age, and the patient was reared as a girl. We speculate that reduced expression of H-Y may have induced aberrant development of the gonads.

Cosyntropin↗

Ontogeny of plasma renin activity in the Dahl rat model of essential hypertension.

Plasma renin activity (PRA) is characteristically lower in the Dahl salt-sensitive (S) rat than in the salt-resistant (R) rat. To establish whether PRA differs between these strains at birth or subsequently becomes suppressed in the Dahl S rat, the ontogeny of PRA was studied in inbred Dahl hypertension-prone (S/JR) and hypertension-resistant (R/JR) rats from 5 to 51 days of age. Pregnant dams and postweaning pups were maintained on diets containing either 0.15% or 0.69% sodium chloride (w:w). Although PRA clearly distinguished the two strains in young adulthood, it was not lower in the S/JR pups at 5 and 15 days of age. However, PRA was greater in rat pups suckling dams consuming the low salt diet. These results suggest that suppressed PRA in S/JR rats is an acquired trait, perhaps occurring secondary to other physiological abnormalities and that maternal diet influences PRA in the suckling Dahl rat.

Animals↗

Morbidity and mortality of coronary bypass grafting in patients 70 years of age and older.

The hospital mortality and major factors contributing to hospital morbidity and postoperative length of stay were examined in 597 consecutive patients 70 years of age and older who underwent isolated coronary artery bypass grafting (CABG) between January, 1978, and December, 1983. The mean age of the patients was 73 years, and 66% were men. Unstable angina was present in 59% of patients, left main coronary disease in 13%, and moderate or severe left ventricular dysfunction in 10%. The mean number of arteries grafted per patient was 3.4. The hospital mortality was 2.7% (16 patients) and was higher than the mortality among 4,125 patients less than 70 years of age (0.4% in 18 patients) operated on during the same interval (p less than 0.001). In multivariate regression analyses, age of 80 years or greater, evolving myocardial infarction, serious coexisting illness, major left ventricular dysfunction, emergent operation, and the development of major postoperative complications were significant (p less than 0.05) independent predictors of increased hospital mortality. Major complications occurred in 135 patients (23%). In multivariate analyses, the presence of vascular disease, serious concomitant illness, and the need for urgent or emergent operation were significant independent predictors of the development of major postoperative complications. The mean duration of postoperative hospital stay was 10.6 +/- 6 (standard deviation) days. In multivariate analyses, the development of major postoperative complications was the only variable independently predictive of prolonged hospital stay. With current techniques, CABG procedures can be safely performed in the elderly with mortality and morbidity rates only slightly higher than those in younger patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

A strain energy function for lung parenchyma.

The strain energy for the air-filled lung is calculated from a model of the parenchymal microstructure. The energy is the sum of the surface energy and the elastic energies of two tissue components. The first of these is the peripheral tissue system that provides the recoil pressure of the saline-filled lung, and the second is the system of line elements that form the free edges of the alveolar walls bordering the alveolar ducts. The computed strain energy is consistent with the observed linear elastic behavior of parenchyma and the data on large deformations around blood vessels.

Air↗

Distortion of submerged dog lung lobes.

The conically shaped caudal lobes of dog lungs were submerged, tip downward in saline, and the lateral surfaces of the lobes were thereby exposed to a hydrostatic gradient in transpulmonary pressure. The force that was required to balance the buoyancy was applied through a clip attached to the tip of the lobe. The locations of metal markers implanted in the parenchyma and attached to the surface were tracked, and regional volume and the horizontal and vertical components of strain were obtained as functions of vertical position. An engineering analysis of the deformation is qualitatively consistent with the data, but the predicted strains are larger than the observed strains. From the experimental and analytical results, we conclude that, for this deformation, the regional volume-local transpulmonary pressure curve closely follows the pressure-volume curve because negative horizontal strains nearly balance the positive vertical strain caused by the buoyancy force.

Animals↗

Interdependence of regional expiratory flow.

Flows from different lung regions interact at the junctions of the bronchial tree, and flow from each region depends on the driving pressures for other regions. At each junction, flow from the region with the higher driving pressure is favored. As a result there is a limit on the difference in alveolar pressures that can develop during expiratory flow from a lung with regional differences in lung compliance and airway resistance. The limiting pressure difference is smaller for lower flow. A nonuniform lung therefore empties more uniformly if it empties slowly, and maximum flow at low lung volume may be greater than it would be at the same lung volume during a maximal expiratory vital capacity maneuver.

Airway Resistance↗