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D F Tierney

Publications and source records attributed to D F Tierney.

At least 19 recordsLinked to original sources
PubMed1990

Effects of ozone inhalation on polyamine metabolism and tritiated thymidine incorporation into DNA of rat lungs.

We examined the effects of low-level ozone (O3) inhalation on polyamine metabolism and tritiated thymidine (3H-TdR) incorporation into DNA in rat lungs. We have also compared the activities of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis, and glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the pentose phosphate cycle and a typical marker of oxidant injury, to assess whether ODC can serve as a sensitive marker of O3 effects on the lung. We exposed 90-day-old male specific-pathogen-free Sprague-Dawley rats to either 0.45 +/- 0.05 ppm (882 +/- 98 micrograms/m3) O3 or filtered room air continuously for 3 days. After exposure, the rats were terminated and the lungs examined for enzyme activities, polyamine contents, DNA content, and 3H-TdR incorporation. We found that in exposed rats, the enzyme activities were significantly increased (p less than 0.05) relative to air controls. G6PD, 25%, ODC, 147%, and S-adenosylmethionine decarboxylase (AdoMet DC), 86%. Polyamine contents were also affected by O3; putrescine increased 80%, p less than 0.05, spermidine did not change, and spermine decreased 23%, p less than 0.05. 3H-TdR incorporation into DNA was significantly elevated, 155%, p less than 0.001, after O3 exposure while total lung DNA content remained unchanged. The concomitant and large increase in ODC activity (reflecting polyamine metabolism) and DNA labeling (reflecting DNA synthesis and/or repair), indicates a strong correlation between the two and suggests that polyamine metabolism may play an important role in the accelerated cell proliferation associated with O3 injury. Moreover, the greater increase in lung ODC activity compared to other enzymes offers a sensitive marker of the lung response to inhaled O3. We conclude that inhalation of O3 at levels similar to what may be encountered during some smog episodes can result in significant pulmonary biochemical alterations with a potential for long-term consequences. The possible association between ODC activity and DNA labeling may offer a new insight into the mechanism of tissue injury and repair. We also speculate that the changes in lung polyamines may reflect antioxidant and anti-inflammatory functions associated with the cellular defense against oxidant injury.

Air↗
PubMed1989

Butyrate increases catalase activity and protects rat pulmonary artery smooth muscle cells against hyperoxia.

A protective effect of butyrate against hyperoxia was found with adult rat pulmonary artery smooth muscle cells. Butyrate (5mM) when added just prior to the hyperoxic exposure (95%) markedly decreased lactate dehydrogenase release from cells during 68 hours of exposure (22% release with butyrate versus 98% without). The uptake and reduction of a tetrazolium compound as another index of cell viability also showed similar improvement with butyrate. Butyrate was associated with a striking increase of catalase to three times the control in the air exposed group while GSH content and the activities of superoxide dismutase and glutathione peroxidase were not significantly changed. In the groups exposed to hyperoxia alone, both enzyme activities were decreased compared to the air exposed controls. When butyrate was present with hyperoxia, the superoxide dismutase was maintained closer to the air exposed control values and the catalase activity remained nearly twice as high as the air exposed control cells. These results suggest that butyrate protects rat pulmonary artery smooth muscle cells from hyperoxia by increasing catalase activity which may help to preserve superoxide dismutase activity. This may be a good model to determine the biological significance of catalase and its interrelationships with other antioxidant systems within the cell.

Animals↗
PubMed1989

Hyperoxia and xanthine dehydrogenase/oxidase activities in rat lung and heart.

Cell injury from hyperoxia is associated with increased formation of superoxide radicals (O2-). One potential source for O2- radicals is the reduction of molecular O2 catalyzed by xanthine oxidase (XO). Physiologically, this reaction occurs at a relatively low rate, because the native form of the enzyme is xanthine dehydrogenase (XD) which produces NADH instead of O2-. Reports of accelerated conversion of XD to XO, and increased formation of O2- formation in ischemia-reperfusion injury, led us to examine whether hyperoxia, which is known to increase O2- radical formation, is associated with increased lung XO activity, and accelerated conversion of XD to XO. We exposed 3-month-old rats either to greater than 98% O2 or room air. After 48 h, we sacrificed the rats and measured XD and XO activities and uric acid contents of the lungs. We also measured the activities of the two enzymes in the heart as a control organ. We found that the activity of XD was not altered significantly by hyperoxia in rat lungs or hearts, but XO activity was markedly lower in the lung, whether expressed per whole organ or per milligram protein, and remained unchanged in the heart. Lung uric acid content was also significantly lower with hyperoxia. The decrease in lung XO activity may reflect inactivation of the enzyme by reactive O2 metabolites, possibly as a negative feedback mechanism. The concomitant decrease in uric acid content suggests either decreased production mediated by XO due to its inactivation or greater utilization of uric acid as an antioxidant. We examined these postulates in vitro using a xanthine/xanthine oxidase system and found that H2O2, but not uric acid, has an inhibitory effect on O2- formation in the system. We therefore conclude that hyperoxia is not associated with increased conversion of XD to XO, and that the exact contribution of XO to hyperoxic lung injury in vivo remains unclear.

Animals↗
PubMed1989

Lung surfactant: some historical perspectives leading to its cellular and molecular biology.

By appreciating the influence of surface forces on lung mechanics, discovering pulmonary surfactant, and then recognizing its deficiency states a small number of investigators began the first 30 years of pulmonary surfactant research. These investigators had different backgrounds and took diverse approaches to understand surface forces in the lung. Their careers provide a fascinating study of the means by which new discoveries are made. After recognizing the critical importance of surfactant, investigators turned to a series of questions that obviously needed to be answered and they attempted to learn the following: 1) how to quantitate surfactant; 2) its biochemical and structural composition; 3) how it leaves the alveolar surface after secretion; and 4) its role in lung diseases. This research established the basis for pursuing the cellular and molecular biology of surfactant.

Animals↗
PubMed1979

Adult respiratory distress syndrome.

Many causes for the adult respiratory distress syndrome (ARDS) have been reported, all with common pathologic, pathophysiologic and biochemical end results. The final common pathway may involve changes in lung content of a critical enzyme, superoxide dismutase, or alterations in surfactant metabolism, or both. The early assumption that the disorder is partially due to oxygen toxicity from inspired oxygen concentrations greater than 60 percent is consistent with findings of recent biochemical studies. Although the lung normally maintains its alveoli dry, during ARDS increased permeability of small pulmonary vessels results in primary pulmonary edema, in contrast to edema from increased vascular pressure. These data have been obtained mainly in animals; whether they apply to humans with ARDS is not certain. Tissue oxygenation is improved by increasing end-expiratory pressure in an animal model of ARDS, more effectively during spontaneous breathing than during mechanical ventilation. During spontaneous breathing, adverse ventilatory effects were caused by stimulation of pulmonary reflexes.

Humans↗
PubMed1979

Oxygen toxicity.

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Animals↗
PubMed1977

Lung lipid metabolism after 7 days of hydrocortisone administration to adult rats.

Pathogen-free rats were given either hydrocortisone (4 mg) or saline by intraperitoneal injection twice daily for 7 consecutive days. Lung weight, body weight, DNA, and total phosphatidylcholine content in lungs were equal in the saline and hydrocortisone groups. Lungs of rats receiving hydrocortisone had 23% more saturated phosphatidylcholine (P less than 0.001) and 7% less unsaturated phosphatidylcholine (P greater than 0.05). When tissue slices of these lungs were incubated with radioactive glycerol and palmitate, the incorporation of radioactivity into saturated phosphatidylcholine from animals given hydrocortisone was significantly higher (P less than 0.001 and P less than 0.05, respectively). Incorporation of radioactivity from lysophosphatidylcholine into phosphatidylcholine was 10 times greater than from glycerol or palmitate, but hydrocortisone had no effect. These results suggest that lysophosphatidylcholine may be an important precursor for phosphatidylcholine synthesis, especially saturated phosphatidylcholine, and hydrocortisone may lead to increased de novo synthesis of phosphatidylcholine.

Age Factors↗
PubMed1977

Air embolism with positive-pressure ventilation of rats.

Although air embolism is known to occur in humans and animals when the lung is overdistended, very few cases have been reported to be associated with positive-pressure ventilation. We have observed that air embolism occurs in rats ventilated with high inspiratory pressures (70 cmH2O) associated with high end-expiratory pressures (10 cmH2O). However, it does not occur in normal rats if the end-expiratory pressure is less than 5 cmH2O or the peak inspiratory pressure is below 60 cmH2O when the frequency of ventilation is 30. Hemorrhagic shock predisposes to air embolism, whereas conditions with pulmonary edema (fluid overloading, lung injury from ventilation with high inspiratory and low expiratory pressures, or oxygen toxicity) decrease the probability of its occurrence.

Animals↗
PubMed1977

Metabolism in rat lung tissue slices: technical factors.

We compared several sets of conditions used to estimate metabolism in rat lung slices. 14CO2 production from [14C]glucose, oxygen consumption, lactate production, and glucose consumption were used as measures of metabolic activity. The calculated results differed when we used 1) different techniques for estimating tissue weight, 2) tissue slices of 0.3-, 0.5-, 0.7-, and 1.0-mm thickness, 3) 95% air or 95% oxygen with 5% CO2 4) a delay after slice preparation and 4 degrees C and room temperature or periods of anoxia before incubation, 5) shaking rates of 60, 90, 120, or 150/min, 6) phosphate or bicarbonate buffers. Conditions of maximal activity were found using 95% O2 with 1.0-mm tissue slices, shaking at 120/min in phosphate buffer without periods of hypoxia or undue delays before incubation. Tissue weight should be obtained without exposure to aqueous solutions or dehydration by contact with cotton gauze or filter paper.

Animals↗
PubMed1977

Regulation of fetal lung phosphatidyl choline synthesis by cortisol: role of glycogen and glucose.

Twenty pregnant rabbits were studied in pairs. Half were given cortisol subcutaneously on days 24, 25, and 26 of gestation in dosage of 2 mg/kg/day. Half served as controls and received saline. The fetal lungs were studied on the 27th day of gestation by incubating lung slices in the presence of [6-14C]glucose. Glucose consumption significantly increased in the tissue from animals treated with cortisol, 17.61 "/- 5.56 (SD) mumol/g in the controls (P less than 0.05). The glycogen content of tissue treated with cortisol was significantly reduced compared to the controls, 2.42 +/- 0.97 (SD) mg/g wet lung versus 3.81 +/- 1.05 (SD) mg/g (P less than 0.05). Treatment with cortisol resulted in significantly enhanced incorporation of the 14C label into glycogen and phosphatidyl choline (Tables 3 and 4). These data suggest that glucocorticoids affect fetal lung phosphatidyl choline production by promoting glycogenolysis and increasing glucose incorporation into phosphatidyl choline.

Animals↗
PubMed1977

Isolated perfused lung--substrate utilization.

Lung metabolism has been extremely difficult to determine in vivo primarily because the lung is overwhelmed by a great blood flow that generally makes the Fick principle inadequate. Largely for reasons such as this, investigators have had to rely on in vitro preparations. The isolated perfused lung has the apparent advantage of being similar to the lung in vivo when compared with other preparations. For instance, there is evidence that the capillary bed of the lung may alter substrates and influence their subsequent metabolism. Substrates have contact with the capillary endothelium in isolated perfused lungs but not to tissue slices, homogenates, or isolated cells. Our studies indicate that precursors of saturated phosphatidylcholine may include lipids, which are hydrolyzed in the capillary of the isolated perfused lung and thus become substrates such as free fatty acids, etc. However, tissue slices do not use the esterified lipids to the same extent, presumably because in this preparation the enzymes in the capillary endothelium do not have contact with the esterified lipids. Substrate utilization of the isolated perfused lung may be considerably altered by inflation of the lung or by pulmonary edema. Although glucose utilization and palmitate oxidation by the isolated perfused lung and by tissue slices of the rat lung are very similar, if the isolated perfused lung develops pulmonary edema, glucose utilization increases by nearly 100%. This phenomenon is apparently not due solely to fluid in the airspaces because in control studies with fluid added into the airways the glucose utilization did not increase to the degree observed with edematous lungs. Lung distention is associated with increased glucose consumption but marked distention is also associated with pulmonary edema. The effect of lung distension may be a direct effect or it may be secondary to the pulmonary edema.

Animals↗
PubMed1976

An intravenous radionuclide method to evaluate hypoxemia caused by abnormal alveolar vessels. Limitation of conventional techniques.

Using conventional concepts, it is possible that a single pathologic entity, pulmonary telangiectases, can produce hypoxia by 3 physiologic mechanisms; shunt, diffusion defect, and ventilation-perfusion abnormalities. The estimation of shunt or shunt-like effect is traditionally calculated by measuring the Po2 of arterial blood during the breathing of 100 per cent 02. This method, however, did not determine blood flow through large alveolar vessels in a patient with familial hemorrhagic telangiectasis who was severely hypoxemic while breathing air. This case served to test the concept that blood flowing through large vessels in the airspaces may be hypoxemic when the patient breathes air, but not 02. Blood flow through these vessles can be estimated by use of radionuclide lung perfusion techniques and estimation of the quantity of radioactive particles that pass through an abnormal pulmonary vascular bed and lodge in kidney and brain. Conventional approaches to estimating blood flow through these fistulas underestimated their effect.

Adult↗
PubMed1975

Pulmonary effects of paraquat in the first day after injection.

To learn whether surface force changes precede the appearance of lung edema during experimental intoxication due to paraquat, we studied rats for 1 day following injection of 27 mg/kg iv. By 24 h, surface-active material recovered by lung lavage was decreased 32 percent, and changes in lung microsections and recoil pressure at half-deflation suggested decreased alveolar stability. Despite a 25 percent loss in overall body weight, lung weight increased more than 7 percent and protein concentration in lung lavage fluid increased by 158 percent. Lung edema was demonstrated morphologically as early as we could detect changes in surfactant or lung mechanical properties. Metabolic studies with lung tissue slices incubated with 4.5 times 10-4 M paraquat showed a fourfold increase in 14CO2 formed from (1-14C) glucose, but no significant change in 14CO2 form (6-14C) glucose, suggesting increased utilization of the pentose pathway for oxidation of glucose. (1-14C) Acetate oxidation was impaired slightly, but incorporation into lipid was decreased by 70 percent. we conclude that paraquat intoxication in the rat is not a suitable model for studying uncomplicated perturbation of the surfactant system.

Acetates↗