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Biomedical subjects

G L Snider

Publications and source records attributed to G L Snider.

At least 127 records · Page 7Linked to original sources
PubMed1984

Computed tomography. An effective technique for mediastinal staging in lung cancer.

Computed tomographic scans of the chest were utilized to stage mediastinal disease in 148 instances of bronchogenic carcinoma considered for resection in 146 patients. Nodes greater than or equal to 1.5 cm in diameter were interpreted as abnormal. All nodes positive by computed tomography were evaluated by mediastinoscopy, anterior mediastinotomy, or thoracotomy. All patients with negative computed tomographic findings underwent thoracotomy without prior surgical staging. Patients undergoing thoracotomy were divided into two groups. In Group I (first 51 instances) routine mediastinal exploration was not carried out; in Group II (last 97 instances) the mediastinum was explored in every patient and nodes were submitted for histopathological study. The computed tomographic and pathological findings on the mediastinal lymph nodes were compared. The sensitivity, specificity, and accuracy of computed tomography in Group I were 88%, 94%, and 92%, respectively, in Group II 75%, 89%, and 86%, and in the combined group, 80%, 91%, and 88%. The positive predictive index in Group I, Group II, and in the combined group was 88%, 69%, and 77%, respectively. It was lower for central than peripheral lesions (74% versus 88%) and was lowest for lesions in the right upper and left lower lobes. The negative predictive index was greater than 90% for all groups and all tumor sites except the left upper lobe, where it was 89%. Ten patients had false-positive scans, three with old mediastinitis and seven with postobstructive pneumonia; nine of the 10 had central lesions, and seven of these lesions were located in the right upper lobe. Eight patients had false-negative scans; six had para-aortic, subaortic, or postsubcarinal nodes. These nodes would not have been accessible to mediastinoscopy. In only one patient with false-negative nodes would routine mediastinoscopy have prevented thoracotomy and resection. Computed tomographic staging of mediastinal disease is indicated for all patients with lung cancer in whom operation is contemplated. Computed tomography directs the most appropriate staging procedure for patients with positive findings and obviates invasive staging for patients with negative findings.

Adult↗
PubMed1983

Functional alpha 1-protease inhibitor in the lower respiratory tract of cigarette smokers is not decreased.

Cigarette smoking is the major risk factor for the development of pulmonary emphysema, a disorder that may result from an imbalance between the elastase and antielastase levels in the lungs. Decreased functional alpha 1-protease inhibitor, an inhibitor of neutrophil elastase, might render smokers susceptible to elastase-catalyzed destruction of pulmonary elastic fibers and the development of emphysema. Binding and inactivation of isotopically labeled porcine pancreatic elastase and human neutrophil elastase by alpha 1-protease inhibitor were measured in fluid obtained by bronchoalveolar lavage of volunteers. The inhibition of elastase-catalyzed solubilization of elastin and a tripeptide substrate were also determined. The mean level of functional alpha 1-protease inhibitor in the bronchoalveolar lavage fluid of smokers was found to be equal to or greater than that of nonsmokers, contradicting reports by other investigators. Increased elastase derived from pulmonary neutrophils, rather than decreased functional alpha 1-protease inhibitor, appears to be the main factor in the genesis of emphysema in smokers.

Adult↗
PubMed1983

Autoradiographic study of 3H-methylated elastase in hamster lungs.

An emphysemalike condition can be induced in animal lungs by the instillation of a single dose of elastase. Autoradiography was used to determine the location of 3H-methylated porcine pancreatic elastase in hamster lungs at four time points. Six hours after instillation of radiolabeled enzyme the distribution of silver grains was very patchy, but in heavily labeled areas grains were concentrated over macrophages, connective tissue areas and over some fibroblasts. By 24 hr the labeling of connective tissue areas was no longer evident and almost all silver grains were associated with macrophages or with the edema fluid that filled many alveoli at this time. By 4 days only macrophages exhibited concentrations of silver grains. The labeling of macrophages was still evident at 7 days. Elastase inactivated by N-acetyl-(L-alanyl)3-L-alanine chloromethyl ketone showed a different distribution 6 hr after instillation. Silver grains were concentrated over macrophages and alveolar type II cells but showed no affinity for connective tissue areas or fibroblasts. By 24 hr almost all grains were located over heavily labeled macrophages.

Animals↗
PubMed1983

The fate of neutrophil elastase incorporated by human alveolar macrophages.

Although protease-antiprotease imbalance is widely thought to contribute to the genesis of emphysema, the involvement of the alveolar macrophage in this process is poorly defined. We have quantified the uptake of radioiodinated human neutrophil elastase by human alveolar macrophages in monolayer culture and assessed the enzyme's fate during periods as long as 48 h after uptake using molecular sieve chromatography. Approximately half of the radiolabel eluted with enzymatically inactive material of molecular sizes corresponding to either degraded or alpha1-protease-inhibitor-bound elastase. The remainder of the radiolabel eluted at 29,000 daltons, in fractions containing enzyme that solubilized particulate elastin, and likely represented intact neutrophil elastase. Macrophages from smokers and nonsmokers showed similar characteristics of incorporation and disposition of neutrophil elastase. Lysates of uncultured alveolar macrophages from smokers and nonsmokers contained (mean +/- SE, n = 4) 7.4 +/- 0.8 and 3.3 +/- 1.4 ng of neutrophil elastase activity per 10(6) cells, respectively (not significant). However, as smokers have 11-fold more cells obtainable by lavage, the total lavaged elastase loads in alveolar macrophages were 561.7 +/- 72.3 and 21.3 +/- 6.8 (p less than 0.01) in smokers and nonsmokers, respectively. We conclude that the alveolar macrophage may clear and inactivate neutrophil elastase in the lung. In addition, by conserving some ingested elastase in an enzymatically active form, the macrophage may serve as an elastase reservoir. In areas of high macrophage density, as around the respiratory bronchioles of smokers, the macrophage could release a portion of the incorporated elastase and damage lung elastin.

Cell Survival↗
PubMed1983

Human neutrophil elastase does not bind to alpha 1-protease inhibitor that has been exposed to activated human neutrophils.

The effect of leukocyte-derived oxidants on the elastase-inhibitory capacity of alpha 1-protease inhibitor was examined in an in vitro system using cells and purified proteins from human sources. The exposure of alpha 1-protease inhibitor to the myeloperoxidase-hydrogen peroxide-halide system resulted in a nearly complete loss of its ability to bind and inactivate purified human neutrophil elastase. A similar loss of binding to and inactivation of human neutrophil elastase was observed on exposure of alpha 1-protease inhibitor to human neutrophils in the presence of a halide and the neutrophil-activating agent, phorbol myristate acetate. This loss of elastase binding activity was abrogated by the addition of azide or catalase but not superoxide dismutase or heated catalase. The data suggest oxidative inactivation of alpha 1-protease inhibitor by secreted myeloperoxidase and hydrogen peroxide. Thus, the reported effects of leukocyte oxidants, especially the myeloperoxidase system, on alpha 1-protease inhibitor have been confirmed using the most pathophysiologically relevant protease, human neutrophil elastase, as the test enzyme. The role of the neutrophil in the pathogenesis of emphysema may, therefore, include the secretion of both elastase and oxidants that impair antielastase defenses.

Blood Proteins↗
PubMed1983

A comparison of the binding and fate of internalized neutrophil elastase in human monocytes and alveolar macrophages.

Human alveolar macrophages (AM) bind and internalize neutrophil elastase (NE) in vitro by receptor-mediated endocytosis. Blood monocytes are progenitors of AM, and if they possess receptors for NE, they could bind and internalize NE in the pulmonary interstitium and may effect elastin degradation, which likely accompanies the development of emphysema. To determine whether monocytes contain receptors for NE, radioiodinated NE (I-NE) binding was assessed, and the results were compared with binding of I-NE to AM obtained concurrently from the same donors. The binding of I-NE to monocytes cultured in vitro for 8 days was also assessed. Specific binding of I-NE to monocytes and AM reached 80% of maximum in 30 min; similar quantities bound to AM and monocytes after a 2-h incubation with I-NE, and a smaller quantity bound to cultured monocytes. The estimated association constant for specific binding was 6 X 10(6)M-1 and 4 X 10(6)M-1 for AM and monocytes, respectively. The fate of I-NE in monocytes and AM at 24 h after uptake was assessed and compared using molecular sieve chromatography. Approximately 50% of the I-NE initially bound to either monocytes or AM remained cell-associated at the end of culture; 62 to 65% of this material eluted at 29,000 daltons and solubilized particulate elastin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

The balance of lung connective tissue elements in elastase-induced emphysema.

Elastase-induced emphysema is associated with changes in all components of connective tissue, including elastin. The abnormal restructuring of lung parenchyma that occurs after elastase administration in hamsters might reflect an abnormal balance of elastin, collagen, and glycosaminoglycan in lung parenchyma. To test this hypothesis, we measured total amounts and levels of accumulation over 24 hr of connective tissue elements in lung explants at several points over a 1-year period after a single elastase treatment in hamsters. We found acute, early changes in the metabolism of elastin, collagen, and glycosaminoglycan consistent with degradation of elastin and increased turnover of collagen and glycosaminoglycan. By day 21 after elastase treatment, lung elastin had returned to control values, then rose and stayed elevated throughout the remainder of the study period. Total collagen levels rose in both control and elastase-treated lungs by the same amount over the year period. However, incorporation of 14C-proline into collagen hydroxyproline was elevated only in elastase-treated lungs over the period of 21 to 360 days. Incorporation of 14C-glucosamine into glycosaminoglycan was greatest over the period of 1 to 5 days after treatment and total levels also peaked at this time. By day 21 both incorporation of glucosamine and total levels of glycosaminoglycan had returned to normal, where they remained. The ratios of glycosaminoglycan to elastin and glycosaminoglycan to collagen were calculated over the period of 21 to 360 days to determine whether the long-term relative balance of these components had changed in elastase-treated lungs. We found that a steady-state imbalance existed between heparan sulfate and collagen and heparan sulfate and elastin, suggesting that an inappropriate amount of heparan sulfate was present relative to the amounts of collagen and elastin. We conclude that administration of elastase results in changes in the long-term balance of lung connective tissue components.

Animals↗
PubMed1982

Chronic necrotizing pulmonary aspergillosis: a discrete clinical entity.

We conclude that chronic necrotizing pulmonary aspergillosis is a clinical entity which has not usually been recognized as one of the forms of pulmonary disease due to Aspergillus species. Patients are middle-aged, and often have some evidence of impairment of host defenses such as diabetes mellitus, a connective tissue disorder, poor nutrition, chronic obstructive lung disease or low dose corticosteroid therapy. They are almost always symptomatic with fever and a productive cough, and their chest roentgenogram shows infiltrative and cavitary disease, typical of a chronic destructive lung process such as tuberculosis or anaerobic infection. Cavity formation is often accompanied by the development of a mycetoma. The disease is usually of 1 to 6 months duration but can be present for years prior to diagnosis. The diagnosis is suggested by the clinical course and the isolation of the fungus from pulmonary secretions; negative cultures for other pathogens and failure to respond to antibacterial or antimycobacterial therapy are characteristic. The diagnosis is confirmed by pathologic evidence of tissue invasion by the fungus or a response to specific antimycotic therapy. The symptomatic response to antifungal chemotherapy, at times combined with surgical drainage or resection, is favorable. However, roentgenographic resolution is not uniform, and many patients have residual cavitary disease. The long-term prognosis is uncertain.

Adolescent↗