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Biomedical subjects

E C Lucey

Publications and source records attributed to E C Lucey.

At least 55 records · Page 3Linked to original sources
PubMed1985

Quantitative study of secretory cell metaplasia induced by human neutrophil elastase in the large bronchi of hamsters.

To explore the time course and the mechanism of development of bronchial secretory cell metaplasia (SCM) induced by human neutrophil elastase (HNE), anesthetized hamsters were injected intratracheally with 300 micrograms highly purified HNE in 0.5 ml saline solution; saline-injected and untreated animals served as controls. At 3, 8, 16, and 21 days after treatment, animals were killed and their lungs fixed by vascular perfusion. Samples from the hilar region of the left lung, containing the main axial airway and its proximal branches, were embedded in Epon-Araldite, and 1 micron sections were stained with methylene blue. Epithelial cells with a luminal border were categorized into three cell types and expressed as a percent of total cells counted (mean 1900 per animal); cells containing at least three mucin granules were classified as secretory, ciliated cells displayed cilia or basal bodies, and cells with none of these characteristics were classified as indeterminate. Percentages of the three cell types in saline-treated animals, at all time points, were comparable to those in the untreated controls. With HNE treatment the secretory cell percentages were higher at 16 days (mean +/- SEM, 36.4% +/- 3.2%) and at 21 days (35.7% +/- 2.9%) than in the untreated animals (18.2% +/- 1.8%, P less than 0.05). The percentage of the indeterminate cells in the HNE group was decreased at days 8, 16, and 21 (7.2% +/- 1.6%, 5.0% +/- 1.4%, and 8.2% +/- 2.5%, respectively) compared with that in the untreated group (21.7% +/- 2.5%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Eglin c, a pharmacologically active elastase inhibitor.

Eglin c is an elastase/cathepsin G inhibitor from leech Hirudo medicinalis. The gene for this 70 aminoacid peptide was synthesized chemically, cloned and expressed by E. coli. Here we report biochemical and pharmacological studies. The rate of complex formation between Eglin c and human leukocyte elastase (HLE) or human cathepsin G (H. Cat. G) was determined and compared to those of a number of other proteinase/proteinase-inhibitor interactions (alpha 1 PI and alpha 2M). The association rate constants of Eglin c with the leukocyte enzymes are of the same order of magnitude as those with the naturally occurring inhibitors alpha 1 PI and alpha 2M. The association rate constant of Eglin c (extracted from leech) and Eglin c (biotechnology product) with HLE was found to be identical. The equilibrium constants Ki of the Eglin c/HLE and the Eglin c/H. Cat. G interactions are in the order of 10(-10) M. In an experiment with the hamster emphysema model, 0.5 mg or 2 mg of Eglin c applied intratracheally one hour before an HLE-insult completely protected the animals against emphysema and no signs of toxicity due to Eglin c were observed.

Animals↗
PubMed1984

Emphysema and bronchial secretory cell metaplasia induced in hamsters by human neutrophil products.

Purified human neutrophil elastase (HNE) and a crude extract of human neutrophils (EXT) were administered intratracheally to hamsters, and their effects were determined 21 and 56 days later by measurement of lung statics and dynamics and by light microscopy and morphometry of the lungs. A dose of 450 micrograms of HNE (HNE 450) produced focal emphysema of moderate severity. The combination of HNE 450 and EXT (HNE 450 + EXT) produced no more severe emphysema than HNE 450 alone; EXT alone did not produce emphysema. The HNE 450, HNE 450 + EXT, and EXT all produced persistent secretory cell metaplasia in large intrapulmonary airways. In a second experiment, 40 micrograms of HNE (elastolytic activity equivalent to that in EXT), designated HNE 40, did not produce secretory cell metaplasia. Neither EXT nor EXT treated with the elastase inhibitor suc-ala-ala-pro-val chloromethyl ketone (EXT + CMK), which had a residual elastolytic activity equivalent to 15 micrograms of HNE, produced emphysema; both preparations caused bronchial secretory cell metaplasia 21 days after treatment. Values of maximal expiratory flow, measured 21 days after treatment, were reduced at points between 20 and 50% of vital capacity for HNE 450 and between 30 and 80% of vital capacity for HNE 450 + EXT; maximal expiratory flows were not significantly different from saline controls for HNE 40, EXT, or EXT + CMK.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Interstitial pulmonary fibrosis induced in hamsters by intratracheally administered chrysotile asbestos. Histology, lung mechanics, and inflammatory events.

The development of interstitial pulmonary fibrosis (IPF) is associated with persistent cellular infiltration and progressive connective tissue accumulation in the alveolar walls. To develop and characterize an animal model of IPF in which pulmonary fibrosis evolves slowly, as well as to develop an inexpensive, easily produced, model of asbestosis, Syrian golden hamsters received single intratracheal injections of either UICC chrysotile asbestos or saline. Animals were then examined at time points up to 180 days for pulmonary histologic and physiologic changes, cytologic characteristics of cells recovered by bronchoalveolar lavage, and spontaneous release of neutrophil chemoattractant activity by alveolar macrophages. Within days after asbestos treatment, hamsters developed a patchy bronchopneumonia centered around terminal airways, which progressed peripherally with time to involve the alveolar walls with persistent inflammation and the gradual development of interstitial and peribronchiolar fibrosis. These histologic changes were accompanied by physiologic findings of air-flow obstruction with air trapping. Bronchoalveolar lavage revealed a persistent neutrophilia that began within 24 h of asbestos treatment; this was associated with the spontaneous release of neutrophil chemotactic activity by cultured alveolar macrophages. In this animal model, pulmonary inflammation and fibrosis can be predictably produced by a single intratracheal instillation of chrysotile asbestos. It represents a useful tool for studying both asbestosis and pulmonary fibrosis in general.

Animals↗
PubMed1982

Pulmonary ventilation and blood gas values in emphysematous hamsters.

Emphysema is known to progress in severity during the year after its induction by pancreatic elastase. A barometric chamber and indwelling aortic cannulas were used to evaluate the effects of worsening emphysema on pulmonary ventilation and arterial blood gases. Unanesthetized, unrestrained hamsters were studied 1, 5, and 13 months after panlobular emphysema was induced by intratracheal injection of porcine pancreatic elastase (0.2 mg in 0.5 ml of 0.15 M NaCl solution/100 g body weight). Lung volumes were subsequently measured in the anesthetized animals and the lungs were examined histologically and stereologically. The pattern of breathing in the 1-month emphysematous hamsters (n = 12) wsa the same as that of untreated control animals (n = 28) but the 5-month (n = 7) and 13-month (n = 6) animals breathed more deeply and slowly; there were no changes in mean inspiratory flow rate of proportion of time per breath occupied by inspiration. The PaO2 for all elastase-treated groups was significantly lower than the control but hypoxemia did not progress significantly with advancing age of the animals. The hematocrit was elevated for the 1-month and 5-month treated animals but not for the 13-month emphysematous animals. The arterial pH and PaCO2 values were not significantly different from control values in any of the three groups of emphysematous animals. We conclude that as hamsters with emphysema age their breathing becomes slower and deeper, that hypoxemia is present from 1 month onwards and does not progress and that hypercapnia is not found at any time.

Aging↗
PubMed1982

Effect of chloromethyl ketone on the progression of elastase-induced emphysema in hamsters.

Intratracheal administration of an elastase inhibitor (Succinyl alanyl alanyl prolyl valine chloromethyl ketone) into hamsters 20 days after induction of emphysema by porcine pancreatic elastase did not affect the lesion seen at 120 days. This study suggests that the progressive increase in lung volume between 20 and 120 days after emphysema induction was not due to a residue of active elastase in the lungs.

Amino Acid Chloromethyl Ketones↗
PubMed1982

Differing susceptibility of young and adult hamster lungs to injury with pancreatic elastase.

A study was undertaken to determine whether there are differences in the initial response of the lungs of young (28 days) and adult (105 days) hamsters to pancreatic elastase treatment. The elastase was given intratracheally (0.1 mg/100 g body weight), and the animals were studied 24 h later. The mean linear intercept of the lungs of young animals increased less than that of adult animals (p less than 0.05). Adult body weights decreased significantly with elastase treatment, whereas those of young elastase-treated animals did not. The lungs of young animals gained proportionately less weight than those of adult animals, suggesting they experienced less hemorrhage and edema. When the volumes, at given transpulmonary pressures, of fluid-filled lungs were expressed as percent predicted, the values for young animals were significantly less than those for adult animals. The most pronounced differences were at low transpulmonary pressures (1 to 3 cm H2O). Volume-pressure hysteresis was not altered by elastase treatment in either the young or adult animals. We conclude that the lungs of adult hamsters are more susceptible to elastase injury than the lungs of young hamsters.

Age Factors↗
PubMed1981

The moderation of elastase-induced emphysema in the hamster by intratracheal pretreatment or post-treatment with succinyl alanyl alanyl prolyl valine chloromethyl ketone.

The capacity of the synthetic elastase inhibitor, succinyl alanyl alanyl prolyl valine chloromethyl ketone (CMK), to moderate elastase-induced emphysema in hamsters was examined using morphometric and physiologic measurements. When 0.5 mg of CMK in saline was injected intratracheally 1 h before the intratracheal injection of 0.1 mg of porcine pancreatic elastase, the hamsters did not develop emphysema. When CMK was injected intratracheally 1 h after elastase, the severity of emphysema was reduced by approximately 50% compared with control animals receiving saline 1 h after elastase. The CMK was ineffective when administered intratracheally 4 h after elastase.

Amino Acid Chloromethyl Ketones↗
PubMed1979

Failure of mechanical properties to parallel changes in lung connective tissue composition in bleomycin-induced pulmonary fibrosis in hamsters.

Lung volumes and volume pressure (V-P) relationships were measured in anesthetized hamsters 8, 30, 60, and 90 days after induction of interstitial pulmonary fibrosis by intratracheal administration of bleomycin. Subsequently, total collagen, elastin, protein, deoxyribonucleic acid (DNA), and dry weight were determined in the lungs of each animal. The mean volume of air in the lungs at a transpulmonary pressure of 25 cm H2O and mean quasi-static compliance were decreased at 8 and 30 days and had returned toward normal by 60 and 90 days. Dry lung weight and total protein content were increased at 8 days, peaked at 30 days, and were still greater than normal at 90 days; DNA peaked at 8 days, remained unchanged through day 60, and returned to normal by day 90. Collagen and elastin content, although not significantly different from control at day 8, was increased at day 30 with peak values attained at day 90. Ratios of collagen or elastin to dry weight, total protein, and DNA were decreased at 8 days, normal at 30 days, and increased at 90 days. The ratios of collagen or elastin to total protein, dry lung weight, or DNA cannot be used as indicators of the amounts of these proteins in the whole lung. We conclude that in interstitial pulmonary fibrosis induced with bleomycin the pattern of changing biochemical composition of the lungs cannot be inferred from the lung volumes or V-P relations.

Administration, Topical↗
PubMed1978

Maximum expiratory flow and transpulmonary pressure in the hamster.

Maximum expiratory flow was measured in 19 normal, anesthetized, tracheostomized, supine hamsters from records of forced deflation produced by the application of varying degrees of negative pressure to the tracheostomies of animals whose lungs had been previously inflated to a transpulmonary pressure (PL) of 25 cmH2O. Flow was measured with a pneumotachograph, volume with a constant-volume pressure plethysmograph and pleural surface pressure (Ppl) with a water-filled esophageal catheter. The esophageal pressure measurement overestimated Ppl and a simple technique was based on an estimate of the resting volume of the chest wall. This volume, at which the Ppl is zero, was calculated for anesthetized supine hamsters from the measurement of respiratory-system pressure and PL made independently of esophageal pressure and was found to be about 30% of vital capacity (VC). Flow limitation was present below 70% of VC with a tracheal deflation pressure of -30cmH2O. Negative effort dependence of flow was seen in small segments of the flow-volume curves. Mean +/- SD maximum expiratory flow at 50% VC was 52 +/- 9.5 ml/s or 9.1 VC/s. Upstream resistance was 0.09 +/- 0.03 cmH2O/ml per s.

Airway Resistance↗