Factors that influence the phenotypic expression of genetically normal and dystrophic muscles.
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Biomedical subjects
Publications and source records attributed to J Butler.
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The possibility that surface tension may affect the hydrostatic transmural pressure of pulmonary vessels and the development of pulmonary edema was studied in anesthetized, open-chested dogs. Isogravimetric pressure (the static intravascular pressure at which transmural osmotic and hydrostatic pressures are balanced such that net fluid flux is zero and lung weight is constant) was measured in nine animals under three conditions: (a) control, normal surface tension, at an alveolar pressure of 30 cm H2O with the apenic lung at room temperature; (b) after increasing surface tension by cooling and ventilating at a low functional residual capacity, at an alveolar pressure sufficient to produce the same lung volume present during control measurements; and (c) after restoring surface tension by rewarming while holding the lung at a high inflation volume, again at the control lung volume. Lung volumes were established from external dimensions and confirmed +/- 10% by deflation spirometry. The isogravimetric pressure (relative to alveolar pressure) was significantly less with increased surface tension than during either the initial control condition (P less than 0.01), or when the surface tension has been restored (P less than 0.01). Similar changes occurred in each of three additional studies performed with control alveolar pressures of 10 cm H2O. Thus, increased surface tension favors fluid leakage presumably because it increases the microvascular transmural pressure.
Serum lipoproteins control cell cholesterol content by regulating its uptake, biosynthesis, and excretion. Monolayers of cultured fibroblasts were used to study interactions with human high density (HDL) and low density (LDL) lipoproteins doubly labeled with [(3)H]cholesterol and (125)I in the apoprotein moiety. In the binding assay for LDL, the absence of specific LDL receptors in type II hypercholesterolemic fibroblasts was confirmed, whereas monolayers of virus-transformed human lung fibroblasts (VA-4) exhibited LDL binding characteristics essentially the same as normal lung fibroblasts. In the studies of HDL binding, specific HDL binding sites were demonstrated in normal and virus-transformed fibroblasts. In addition, type II hypercholesterolemic cells, despite the loss of LDL receptors, retained normal HDL binding sites. No significant competition was displayed between the two lipoprotein classes for their respective binding sites over a 5-fold concentration range. In VA-4 cells, the amount of lipoprotein required to saturate half the receptor sites was 3.5 micro g/ml (9 x 10(-9) M) for LDL and 9.1 micro g/ml (9 x 10(-8) M) for HDL. Pronase treatment reduced LDL binding by more than half but had no effect on HDL binding. Chloroquine, a lysomal enzyme inhibitor, stimulated net LDL uptake 3.5-fold by increasing internalized LDL but had essentially no effect on HDL uptake. Further experiments were conducted using doubly labeled lipoproteins to characterize the interaction of LDL and HDL with cells. While the cholesterol and protein moieties of LDL were incorporated into cells at similar rates, the uptake of the cholesterol moiety of HDL was 5 to 10 times more rapid than that of the protein component. Furthermore, the apoprotein component of LDL is extensively degraded following exposure, whereas the apoprotein moiety of HDL retains its macromolecular chromatographic characteristics. These results indicate that HDL and LDL bind to cultured cells at separate sites and that further processing of the two lipoprotein classes appears to take place by fundamentally different mechanisms.-Wu, J-D., J. Butler, and J. M. Bailey. Lipid metabolism in cultured cells XVIII. Comparative uptake of low density and high density lipoproteins by normal, hypercholesterolemic, and tumor virus-transformed human fibroblasts.
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Application of positive end-expiratory pressure to dogs with noncardiogenic pulmonary edema increased intracranial pressure (measured as cerebrospinal fluid pressure) and decreased cerebral perfusion pressure. The magnitude of these changes depended on the amount of end-expiratory pressure applied and the lung compliance.
Edema transudation from extra-alveolar vessels was investigated in anesthetized, open-chested dogs. Fluid accumulation at different alveolar and extra-alveolar vascular pressures was assessed by continuous lung weighing and microscopy. The left (experimental) lung was distended with 6% CO2 and air while normal arterial blood gases were maintained by separately ventilating the right lung. Extra-alveolar vessels were isolated by compressing alveolar vessels with alveolar pressures high enough to stop blood flow. Weight increased steadily (edemogenesis) when pulmonary arterial and/or pulmonary venous pressure was 1 cmH2O below this pressure. Because some alveolar vessels at the lung base could have remained open and leaked, extra-alveolar vessels were also separated from alveolar vessels by glass bead embolization sufficient to stop perfusion. Lung weight gains followed selective pulmonary arterial or venous pressure elevations. Electron microscopy demonstrated edema in experimental lobes which was not present in control lobes with undistended extra-alveolar vessels at the same alveolar pressure. Thus pulmonary edema can be caused by fluid leaking from extra-alveolar vessels.
We have measured the static and dynamic transmural pressures of extrapulmonary airways during positive pressure lung inflation in anesthetized dogs suspended in the standing position. Thin, fluid-filled catheters measured pressures within and on the anterior surface of the airways in the mediastinum and neck. The change from mediastinal to cervical static extra-airway pressures (Pea) was not abrupt but occurred through the thoracic outlet and the root of the neck. The static Pea in the mediastinum was more positive than pleural pressure when lung volume was increased with positive pressures. During forced deflation equal pressure points (EPP) were in labor bronchi from which airway narrowing extended towards the mouth. Under these conditions, the dynamic mediastinal Pea mouthward of the EPP remained close to pleural pressures even at high volumes. This suggested that forces of restitution generated in the surrounding tissues by the narrowing of the airways did have a small effect in reducing the pressure affecting their anterior surface.
We have studied the effect of the ventrical height of the pulmonary wedge catheter in the lung on the pulmonary wedge pressure-left atrial relationship during positive end-expiratory pressure ventilation in oleic acid-induced pulmonary edema. Pulmonary wedge catheters were placed above and below the left atrium in normal dogs and in dogs with oleic acid-induced edema. Wedge pressure and left atrial pressure were measured simultaneously during positive end-expiratory pressure ventilation (range, 0 to 30 cm H2O positive end-expiratory pressure). Pulmonary wedge catheters below the left atrium correctly recorded left atrial pressure and change in left atrial pressure at all positive end-expiratory pressures studied. Pulmonary wedge catheters above the atrium consistently recorded pressures higher than the normal left atrial pressure. They did not correctly respond to increases in left atrial pressure until it was increased to a value higher than the initial upper pulmonary wedge pressure. Pulmonary arterial catheters, when properly placed, should be reliable indicators of left atrial pressure during positive-pressure ventilation in normal and edematous lungs.
Four hundred patients aged at least 17 who came to Casualty in one year after deliberately poisoning themselves were randomly assigned between an Experimental social work service (task-centered casework) and a Control (routine) follow-up service. 139 patients were excluded from the trial, most of whom were already in continuing psychiatric treatment. After one year there was no difference in the proportions of E and C patients who repeated self-poisoning (about 14 per cent), but significantly more of the excluded group had repeated (36 per cent). A random half of the trial patients were re-interviewed four months after admission. Both E and C groups had improved to a significant extent on measures of depressed mood and of social problems. E patients showed more change in social problems and were more satisfied with the service they had received.
A highly reproducible model of fulminant hepatic failure was developed by administering intravenously the selective hepatotoxin galactosamine hydrochloride (4.25 mmoles per kg) to genetically uniform rabbits. The great majority of rabbits died between 21 and 44 hr after injection following a period of coma which lasted 2.6 hr on average. Serum biochemical tests and liver histology reflected massive hepatic injury. Changes in plasma ammonia and amino acid concentrations, in coagulation parameters, and in the electroencephalogram were similar to those found in human fulminant hepatic failure. This model appears promising for future studies of the pathogenesis and treatment of fulminant hepatic failure.
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Fetal heart rate (FHR) variability is thought to be an important index of fetal health. In the presence of normal variability, the fetus is vigorous, but lack of beat-to-beat variability may be associated with fetal compromise. A distinction between short-term variability (STV) (beat-to-beat changes between successive beats) and long-term variability (LTV) (rhythmic fluctuations in FHR) has not been made to date. We have utilized computer programs to compare three pairs of mathematical indices and one visual index of FHR variability. Among the three pairs of indices designed for detection of STV and LTV, de Haan's short-term and long-term indices exhibited the least interdependence, and the long-term index was completely insensitive to artifically generated pure STV. Yeh's short-term and long-term indices exhibited substantial positive interdependence. Hon's visual index appears to detect LTV primarily rather than STV. When the effect of progression of labor on FHR variability was examined, no conclusions were possible because of inconsistencies between patients. Ultimately, the clinical value of any one of these indices awaits testing of their ability to define fetal well-being or fetal distress.
1. Hydrated electrons, produced by pulse radiolysis react with porphyrin cytochrome c with a bimolecular rate constant of 3-10(10) M-1 S-1 at 21 degrees C and pH 7.4. 2. After the reduction step an absorbance change with a half-life of 5 microns is observed with the spectral range of 430-470 nm. A relatively stable intermediate then decays with a half-life of 15 s. 3. The spectrum of the intermediate observed 50 microns after the generation of hydrated electrons shows a broad absorption band between 600 and 700 nm and a peak at 408 nm. The spectrum is attributed to the protonated form of an initially produced porphyrin anion radical. 4. Reduced porphyrin cytochrome c reacts with ferricytochrome c with a bimolecular constant of 2-10(5) M-1- S-1 in 2 mM phosphate pH 7.4, at 21 degrees C and of 2 - 10(6) M-1-S-1 under the same conditions but at 1 M ionic strength. It is proposed that electron transfer in an analogous exchange reaction between ferrocytochrome c and ferricytochrome c occurs via the exposed part of the haem.
1. The hydrated electron reacts with ferrocytochrome c to form an unstable intermediate. This intermediate decays in a first-order manner to give, in the first instance, a product which has a similar absorption spectrum in the range 400-610 nm as normal ferricytochrome c. 2. At 21 degrees C the rate constant for the reaction of hydrated electrons with ferrocytochrome c at pH 7.4 (2 mM phosphate buffer) is (3.0 +/- 0.3) = 10(10) M-1 - S-1. As the pH is increased above pH 8.0 the rate constant steadily decreases. The dependence of the rate constant on pH can be explained if ferrocytochrome c has a pK of around 9.2. 3. At 21 degrees C and pH 7.4, the rate constant for the decay of the intermediate is (1.40 +/- 0.15) - 10(5) S-1. This reaction shows no pH dependence in the range 6-2-11.0. 4. A mechanism is proposed whereby the central metal atom of the ferrocytochrome c is oxidased and a thioether bond is reduced. The resulting ferricytochrome c species then slowly develops an absorbance at 606 nm due to the attack of the sulfhydryl group on the haem.
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We have studied a patient with 5-oxoprolinuria who presented with hemolysis and metabolic acidosis as a neonate; he has had normal growth and development to one year of age. Compensated hemolytic anemia persists, and he requires alkalinizing agents for correction of acidosis. Biochemical studies have confirmed that a deficiency of glutathione synthetase is responsible for the 5-oxoprolinuria. Genetic heterogeneity was apparent on comparative study of glutathione synthetase kinetics in cells from two patients with this disorder. The consequences of the deficiency of glutathione synthetase, decreased intracellular glutathione, and overproduction of 5-oxoproline are discussed with reference to the possible cellular roles of these compounds.
In the presence of regional atelectasis, hemorrhage increases the pulmonary shunt fraction (Qs/Qt). We wanted to determine if the increase in Qs/Qt occurs due to inhibition of hypoxic vasoconstriction or due to hydrostatic effects associated with a collapsed lung and decrease in cardiac output. We compared the effects of hemorrhage on flow to a hypoxic lung (Qh) produced in two ways in anesthetized dogs. In six dogs atelectasis of one lung was produced by bronchial occlusion and in a second group of six dogs one lung was ventilated with 100% nitrogen. The other lung in each group was ventilated with 100% nitrogen. The other lung in each group was ventilated with 100% O2. Hemorrhage (20 ml/kg) had no effect on Qh/Qt in dogs with a nitrogen-ventilated lung suggesting that hemorrhage did not inhibit hypoxic vasoconstriction. In contrast, hemorrhage caused a marked increase in Qh/Qt in dogs with a collapsed lung because the flow to the inflated ventilated lung fell, while flow to the collapsed lung did not change. The increase in Qs/Qt in the dogs with atelectasis can be explained solely on the basis of mechanical effects produced by the differences in lung heights and alveolar pressures between ventilated and atelectatic lung.