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Biomedical subjects

T A Wilson

Publications and source records attributed to T A Wilson.

At least 19 recordsLinked to original sources
PubMed1992

Correlation between puberty and the development of autoimmunity to spermatozoa in men with cystic fibrosis.

OBJECTIVE: To test the hypothesis that puberty is a necessary factor in the pathogenesis of autoimmunity to sperm in men with cystic fibrosis (CF), we studied prepubertal and postpubertal males with CF versus an age-matched group of males with type 1 diabetes as controls. DESIGN: Sera from CF and diabetic males treated at University Hospital, State University of New York, Stony Brook, were tested by indirect immunobead binding for antisperm antibodies and by radioimmunoassay for testosterone (T), luteinizing hormone, and follicle-stimulating hormone. The finding of autoantibodies to spermatozoa was correlated with chronological age, as well as with clinical and hormonal pubertal status. RESULTS: Autoimmunity to sperm, as detected by humoral antisperm antibodies, was documented solely in postpubertal males, as judged by hormonal and clinical criteria. Eighty-three percent of sexually mature CF males and 6.3% (1 of 16) diabetic males exhibited autoantibodies to sperm. These antibodies were only detected when serum T levels were > 8.7 nmol/L (250 ng/dL). CONCLUSIONS: These results suggest that puberty, and presumably, active spermatogenesis is a requirement for the development of autoimmunity to sperm in men with CF.

Adolescent↗
PubMed1992

Contributions of ventilation and perfusion inhomogeneities to the VA/Q distribution.

The anatomic distributions of ventilation (VA) and perfusion (Q) in prone and supine dogs have been described in the literature. These data also provide frequency distributions, i.e., the distribution of lung units as a function of VA or Q. A comprehensive distribution that encompasses these two distributions is described, and the properties of the comprehensive distribution that determine the width of the VA/Q distribution are identified. Using data on the VA and Q distributions taken from various sources in the literature, we estimated the widths of the VA/Q distributions. The widths estimated from the independent data on the VA and Q distributions agree well with the widths obtained from gas exchange data. The analysis provides information about the relative contributions of the VA and Q distributions to the width of the VA/Q distribution. In the prone dog, the VA and Q distributions, as described by the available data, have different length scales, and we argue that these distributions are therefore not highly correlated. As a result, the variance of the VA/Q distributions is approximately the sum of the variances of the VA and Q distributions. Two-thirds of the variance in VA/Q is a result of nonuniform Q, and one-third is a result of nonuniform VA. In the supine dog, the variance of VA is larger than in the prone dog because of a vertical gradient and the variance of Q is larger, in part, because of a vertical gradient. Because the magnitudes of the vertical gradients of VA and Q are about equal, the vertical gradient of VA/Q is small, and these components of the VA and Q inhomogeneities contribute little to the width of the VA/Q distribution. The other components of Q inhomogeneity cause the additional variance of VA/Q in the supine dog.

Analysis of Variance↗
PubMed1992

Parenchymal stability.

Both continuum and micromechanical models have been used to describe the mechanics of lung parenchyma. Different authors, using different models, have come to different conclusions about parenchymal stability. We show that the continuum model, augmented by bounds on the elastic moduli obtained from recent micromechanical modeling, yields the same conclusions about stability that have been obtained from purely micromechanical modeling: if the lung were homogeneous, it would be stable; local atelectasis would not occur at positive transpulmonary pressure. However, the same analysis yields the prediction that if the surface-to-volume ratio is not uniform throughout the lung, regions of higher surface density collapse if surface tension is large and insensitive to surface area. A micromechanical model that illustrates regional collapse is described.

Humans↗
PubMed1992

Effect of respiratory muscle tension on lung volume.

The chest wall is modeled as a linear system for which the displacements of points on the chest wall are proportional to the forces that act on the chest wall, namely, airway opening pressure and active tension in the respiratory muscles. A standard theorem of mechanics, the Maxwell reciprocity theorem, is invoked to show that the effect of active muscle tension on lung volume, or airway pressure if the airway is closed, is proportional to the change of muscle length in the relaxation maneuver. This relation was tested experimentally. The shortening of the cranial-caudal distance between a rib pair and the sternum was measured during a relaxation maneuver. These data were used to predict the respiratory effect of forces applied to the ribs and sternum. To test this prediction, a cranial force was applied to the rib pair and a caudal force was applied to the sternum, simulating the forces applied by active tension in the parasternal intercostal muscles. The change in airway pressure, with lung volume held constant, was measured. The measured change in airway pressure agreed well with the prediction. In some dogs, nonlinear deviations from the linear prediction occurred at higher loads. The model and the theorem offer the promise that existing data on the configuration of the chest wall during the relaxation maneuver can be used to compute the mechanical advantage of the respiratory muscles.

Body Weight↗
PubMed1992

Once-daily ceftriaxone to complete therapy of uncomplicated group B streptococcal infection in neonates. A preliminary report.

Newborn infants minimally symptomatic with non-central nervous system (CNS) infections due to Streptococcus agalactiae (group B streptococcus [GBS]) and other pathogens may not require skilled nursing care during the entire course of parenteral antibiotic therapy. In 1985, treatment guidelines were made available to private practitioners in Oregon for therapy of newborn infants at low risk of complications from their infections. In 1988, patient data were collected and analyzed retrospectively. Outpatient management during convalescence of 51 infants (21 with culture-positive infections due to GBS) was accomplished with once-daily physician follow-up examinations and IM injection of ceftriaxone. Long-term (greater than or equal to two months) follow-up data were available for 67% of GBS-infected infants, with no complication of infection or significant complication of therapy reported. Outpatient parenteral antibiotic management of selected, low-risk infants may offer the clinician an alternative to hospitalization for a portion of the duration of parenteral antibiotic therapy.

Ceftriaxone↗
PubMed1992

Molecular biology of the leukaemia inhibitory factor gene.

Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine that has been identified and characterized in several laboratories by virtue of a number of different biological activities. LIF is encoded by a unique gene located at 11A1 in the mouse and at 22q12 in man. However, loci related to sequences in the 3' untranslated region of the mRNA have been detected and located elsewhere in the genome. The LIF gene from four mammalian species has been cloned and sequenced; the sequences are highly conserved within the coding regions and largely non-conserved within the non-coding regions. However, a number of non-coding segments displaying high interspecies similarity are evident; these are candidate control regions. Intriguingly, an exon corresponding to the 5' end of a variant LIF transcript in the mouse that encodes a potentially matrix-associated form of LIF is not conserved in the human, ovine and porcine genes. The promoter region of the LIF gene contains four well-conserved TATA elements, and two start sites of transcription have been identified. Three regions within the 5' flanking region have been identified as important for the function of the LIF promoter, including a candidate repressor sequence. The LIF gene is transcribed at only very low levels in normal tissues, but its expression can be increased by various stimuli.

Amino Acid Sequence↗
PubMed1992

Thoracic disk herniation.

Symptomatic thoracic disk herniation is unlikely to be encountered with significant frequency in clinical practice. Subtle manifestations required a high index of suspicion if the work-up is to be efficient. In the appropriate candidate, magnetic resonance imaging is the best screening tool, and it may be the only diagnostic study required. In the symptomatic patient with neurologic dysfunction or persistent pain refractory to nonsurgical therapy, surgical diskectomy is a safe and effective treatment with limited morbidity.

Adult↗
PubMed1991

Gravitational forces on the chest wall.

The gravitational work of breathing was determined by measuring the vertical motion of body mass. The subject, seated or lying supine on a force platform, performed breathing maneuvers in which rib cage volume (Vrc) and abdominal volume (Vab) were changed in varying proportions. The increment in the vertical force exerted on the platform and Vrc and Vab were measured over the course of each maneuver. The force signal was integrated twice with respect to time to obtain the change in the product of mass and height of the subject. This was multiplied by the gravitational acceleration to obtain the change in the gravitational potential (Ug). Simultaneous values of Ug, Vrc, and Vab were taken from the data, and the values of the coefficients for which the following equation best fit these values were determined: Ug = a1 Vrc + a2 Vab + (1/2)a11 Vrc2 + a12 Vrc Vab + (1/2)a22 Vab2. The coefficients a1 and a2 can be interpreted as the values of the expiratory gravitational forces on the rib cage and abdomen, respectively. In the seated posture, the force on the rib cage is expiratory and the force on the abdomen is inspiratory; the magnitudes of both are approximately 8 cmH2O. In the supine posture, both are expiratory forces of approximately 9 cmH2O. The coefficients of the quadratic terms in Ug are all positive, and the gravitational work per unit volume of chest wall expansion increases with increasing volume in both postures. The coefficients of the quadratic terms can be interpreted as gravitational contributions to the elastances of the compartments.

Acceleration↗
PubMed1990

Deformation of the dog lung in the chest wall.

Data on the shape of the chest wall at total lung capacity (TLC) and functional residual capacity (FRC) were used as boundary conditions in an analysis of the deformation of the dog lung. The lung was modeled as an elastic body, and the deformation of the lung from TLC to FRC caused by the change in chest wall shape and gravity were calculated. Parenchymal distortions, distributions of regional volume at FRC as a fraction of the volume at TLC, and distributions of surface pressure at FRC are reported. In the prone dog there are minor variations in fractional volume along the cephalocaudal axis. In transverse planes opposing deformations are caused by the change of shape of the transverse section and the gravitational force on the lung, and the resultant fractional volume and pleural pressure distributions are nearly uniform. In the supine dog, there is a small cephalocaudal gradient in fractional volume, with lower fractional volume caudally. In transverse sections the heart and abdomen extend farther dorsally at FRC, squeezing the lung beneath them. The gradients in fractional volume and pleural pressure caused by shape changes are in the same direction as the gradients caused by the direct gravitational force on the lung, and these two factors contribute about equally to the large resultant vertical gradients in fractional volume and pleural pressure. In the prone position the heart and upper abdomen rest on the rib cage. In the supine posture much of their weight is carried by the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗