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Biomedical subjects

G L Snider

Publications and source records attributed to G L Snider.

At least 19 recordsLinked to original sources
PubMed1992

Covalently linking a peptidyl carbamate elastase inhibitor to a hydrophilic polymer increases its effectiveness in preventing emphysema and secretory cell metaplasia in the hamster.

A peptidyl carbamate, p-nitrophenyl N-(succinyl-L-alanyl-L-alanyl-L-prolyl-methyl)-N-isopropylcarbamate++ + (PCI) was tested for its ability to inhibit the elastolytic activity of human neutrophil elastase (HNE) and to prevent HNE-induced emphysema and secretory cell metaplasia in the hamster. In vitro, 50% of the elastolytic activity of 10 micrograms of HNE was inhibited by 0.9 micrograms of PCI, a molar ratio of PCI to HNE of 4.5. Bronchoalveolar lavage of hamsters receiving PCI intratracheally showed a rapid decrease in HNE inhibitory activity (4 min for 50% decrease), suggesting rapid clearance, binding, or inactivation of the PCI. Instillation of 300 micrograms of HNE combined with 100, 500, or 3,000 micrograms PCI, a 16-, 83-, and 503-fold molar excess of PCI, respectively (molar ratios of 17, 84, and 504), suppressed HNE-induced lung hemorrhage, but it did not moderate HNE-induced emphysema despite the large molar excess of inhibitor. When PCI was covalently bound to a linear hydrophilic polymer of alpha,beta-poly[N(2-hydroxyethyl)-D,L-aspartamide], producing a polymer-bound carbamate inhibitor (PPCI) of HNE, the time for a 50% decrease of PPCI functional activity from the hamster lung lavage was 421 min. Instillation of 100 micrograms of PPCI 1 h before instillation of 300 micrograms HNE resulted in significant amelioration of emphysema; 900 micrograms of PPCI was required to obtain amelioration of bronchial secretory cell metaplasia. The larger dose of PPCI also provided significant amelioration of emphysema when the interval between PPCI and HNE administration was 8 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Parker B. Francis Lecture. Animal models of chronic airways injury.

Airways SCM is induced by a wide variety of noxious agents that perturb but do not kill the epithelial cells. Discharge of mucus soon after first exposure to a noxious agent is frequently observed, but discharge of mucus may or may not be followed by development of SCM. Treatment with steroidal and nonsteroidal antiinflammatory agents protects against development of SCM in some models, such as tobacco smoke-induced SCM, but not in others, such as enzyme-induced SCM. In general, SCM regresses slowly or not at all spontaneously. Recovery of some models, such as tobacco smoke-induced SCM, is hastened by nonsteroidal antiinflammatory agents. Experimental protection against induction of enzyme-induced SCM by secretory leukocyte protease inhibitor, which is secreted by airways secretory cells, suggests that such protection may be the in vivo role of that antiprotease. The response of the airways to injury is heterogeneous, with patterns of response of the secretory cells varying according to agent, species, and longitudinal localization of epithelial cells in the airways. The longitudinal heterogeneity of response of secretory epithelial cells to injury is summarized in Table 1. Anatomic heterogeneity of epithelial cells may make a minor contribution to longitudinal variation in response of secretory cells to injury. Molecular heterogeneity of the cellular milieu seems the more likely explanation for this variation in cellular response.

Animals↗
PubMed1979

Pleuropericardial reaction to treatment with dantrolene.

Chronic pleural effusion occurred in three patients, one of whom also developed acute pericarditis. A fourth patient developed both pleural and pericardial effusions. All patients had been receiving dantrolene sodium for at least two months. The pleural fluid was a sterile exudate with pleural and peripheral blood eosinophilia in all patients. No pulmonary parenchymal involvement was apparent. Pleural biopsy specimens showed nonspecific inflammation. Resolution of the pleural process was prolonged after dantrolene therapy was discontinued. Although a causal relationship between dantrolene and serosal inflammation remains unproved, this association in four patients warrants careful observation of others receiving long-term dantrolene therapy.

Acute Disease↗
PubMed1979

Bronchiolitis and bronchitis in connective tissue disease. A possible relationship to the use of penicillamine.

Rapid onset of severe and irreversbile airflow obstruction developed in two women. One had eosinophilic fasciitis and the other had rheumatoid arthritis. Both were treated with penicillamine. In the first patient, aged 42 years, dyspnea developed after six months of therapy. Her roentgenogram showed hyperinflation. Forced vital capacity expired in one second (FEV1/FVC%) decreased from 75% to 40%, and the residual volume increased by 1 L. In the second patient, aged 54 years, cough and dyspnea developed after ten months of therapy. The FEV1/FVC% was 56%, the FEV1 was 0.9 L, and the roentgenogram was normal. Lung biopsy specimens demonstrated severe and widespread bronchiolitis. An association between obliterative bronchiolitis and rheumatoid arthritis has been reported. Penicillamine may impair healing of bronchiolitis in such patients.

Adult↗
PubMed1979

Respiratory therapy. Current practice in ambulatory patients with chronic airflow obstruction.

The role of respiratory therapy in treating ambulatory patients with chronic obstructive pulmonary disease is becoming more clearly defined. Oxygen therapy on a continuous basis is needed for patients with arterial PO2 values below 45 mm Hg and should be considered for patients with arterial PO2 values between 45 and 55 mm Hg who have chronic cor pulmonale, erythrocytosis with hematocrit value greater than 55%, and disturbances of cognition and sleep. Concentrated bronchodilator and corticosteroid aerosols have established roles in therapy; the place of bland aerosols is less clear They may increase ease of expectoration and should be given by simple compressed-air nebulizer systems; their administration by brief periods of intermittent positive-pressure breathing is rarely justified. Three-positional, postural drainage with chest percussion and vibration may be helpful in mobilizing secretions in patients with severe disease.

Aerosols↗
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↗
PubMed1979

The dose-dependent fate of enzymatically active and inactivated tritiated methylated pancreatic elastase administered intratracheally in the hamster.

Hamsters were intratracheally instilled with saline solutions containing a high dose (145 to 220 micrograms) or a low dose (1.3 to 1.5 micrograms) of 3H-methylated pancreatic elastase or N-acetyl-(L-alanyl)3-L-alanine chloromethyl ketone-inactivated 3H-methylated pancreatic elastase. Only the lysyl residues of the elastase molecule were methylated and radiolabeled in a nonlabile manner. The 3H-methylated elastase preparation exhibited esterolytic and elastolytic activity, spectral properties, and emphysema-inducing properties indistinguishable from those of unmodified pancreatic elastase. There was no detectable hemorrhagic or emphysematous reaction with the inactivated 3H-methylated elastase, and this material was cleared from the lungs 11 times faster than the corresponding enzymatically active high dose of 3H-methylated elastase and 18 times faster than the corresponding enzymatically active low dose of 3H-methylated elastase. There were correspondingly higher amounts of radioactivity in the urine of hamsters treated with the inactivated elastase. All of the 3H radioactivity recovered from the urine was associated with epsilon-N-methyllysyl and epsilon-N,N-dimethyllysyl residues. Significant levels of radioactivity were found in the cells, primarily alveolar macrophages, lavaged from the lungs. The low dose of enzymatically active elastase caused neither detectable hemorrhage nor emphysema, both of which were associated with the high dose. At 144 days significant radioactivity (1,200 cpm) remained in the lungs of animals treated with high or low doses of enzymatically active elastase, whereas virtually no radioactivity (100 cpm) was found in the lungs of those treated with high or low doses of inactivated elastase. The data presented support the hypothesis that the formation of elastase complexes with alpha 1-protease inhibitor and alpha 2-macroglobulin is associated with the slower clearance and the retention of significant amounts of radioactivity in the lungs. Some of the residual radioactivity found in the hamster lungs might represent enzymatically active elastase complexed with alpha 2-macroglobulin and might offer an explanation for the progressive nature of emphysema induced by a single dose of elastase.

Animals↗
PubMed1978

Differentiation of pleural and pulmonary lesions using computed tomography.

We report an analysis of computed tomography (CT) of the thorax in 75 patients with combinations of pleural and parenchymal disease or complex pleural shadows. These patients were among more than 300 with pulmonary disease examined by this method. Twenty-eight percent of the 75 scans within this group were classified as high value, contributing information which was not available from other clinical or roentgenographic data, and which directly altered the management, diagnosis, or prognosis of these patients. Forty percent of the scans were classified as of intermediate value, contributing to better understanding of the case but with no major influence on patient management or prognosis. Thirty-two percent of the scans added no additional information to the chest roentgenograms. Thirty-seven percent of the 46 scans done specifically to differentiate pleural from parenchymal disease were classified as of high value, but only 14% of the scans in patients with pleural fluid loculations or pleural masses were placed in this category. We conclude that thoracic CT provided information not otherwise available in one third of the patients with complex combined pleural and parenchymal disease examined in our series.

Adult↗
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↗
PubMed1978

The fate of newly synthesized lung collagen after endotracheal administration of C-proline to hamsters.

The endotracheal administration of 14C-proline to young adult golden hamsters was effective in radiolabeling collagen and resulted in a greater specific activity for hydroxyproline than did intraperitoneal administration of the amino acid. The isolation of purified isoluble collagen was accomplished with the aid of pancreatic elastase. Enzyme treatment of lung homogenates resulted in the solubilization of 35 per cent of total lung collagen. The residue obtained after elastase treatment was pure collagen. A significant portion of the radiolabeled collagen was solubilized by the elastase treatment, which suggests that elastase may be helpful in distinguishing between newly synthesized and total lung collagen. Studies performed at various times after administration of 14C-proline indicate that a greater portion of the collagen radioactivity is solubilized during the early days after treatment with the amino acid. The methodology and procedures outlined in this communication allow for additional insights into the metabolism of connective tissue, specifically collagen, in normal and diseased lungs.

Animals↗