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Biomedical subjects

J B Gee

Publications and source records attributed to J B Gee.

At least 19 recordsLinked to original sources

Asbestos in New York City public school buildings--public policy: is there a scientific basis?

The most recent of New York City's asbestos emergencies occurred in the late summer of 1993. It prevented schools from opening that fall, precipitated much media excitement, and caused a flurry of widespread abatement activities. This resulted in large measure from the U.S. Environmental Protection Agency's subjective school building inspection policy concerning identification of asbestos hazards in buildings and the subsequent Asbestos Hazard Emergency Response Act mandate for inspection. Data on concentrations of asbestos in the air, important for the calculation of risk to building occupants, were not required and therefore not obtained, as part of the abatement strategy or priority setting. Based on fiber-in-air measurements obtained elsewhere, the calculated risk to NYC school children, using the most pessimistic models, was less than six excess cancer deaths per million lifetimes equivalent to smoking less than a dozen cigarettes in a lifetime. The NYC administration responded to pressure from parent groups concerned with perceived asbestos risks to their children by closing the schools. The hysteria occurred because much of EPA's policy lacked a scientific basis for risk evaluation and assessment.

Air Pollution, Indoor

An analysis of the inter-relationships among multiple bronchoalveolar lavage and serum determinations, physiologic tests, and clinical disease activity in patients with sarcoidosis.

Analysis of epithelial lining fluid from the lungs of patients with sarcoidosis frequently suggests the presence of an alveolitis. Several markers of this inflammatory response were quantitated in bronchoalveolar lavage fluid and serum from 45 non-smoking patients with sarcoidosis. All markers were elevated significantly compared to those from 19 normal controls. The degree of statistical correlation among all data was assessed. Pulmonary function tests, 67Gallium lung scans, and a clinical index of disease activity also were quantitated. When patients were grouped by the number of abnormal BAL lavage and serum markers, those patients with elevated values of five or more of these markers had significantly worse clinical disease and lower carbon monoxide diffusing capacities. These results indicate that pulmonary sarcoidosis is an immunologically heterogeneous disease and that measurement of several markers of disease activity may be required to accurately estimate the activity of the lung disease.

Adult

Asbestos: scientific developments and implications for public policy.

Asbestos is a commercial term for a group of fibrous minerals often associated with the development of pulmonary interstitial fibrosis (asbestosis), lung cancer, and malignant mesothelioma in occupationally exposed individuals. The pathogenicity of different forms of asbestos varies--long, thin amphibole fibers are most pathogenic, particularly in the induction of mesothelioma. Available data do not support the concept that low-level exposure to asbestos is a health hazard in buildings and schools. The concentration of asbestos fibers in air, type of asbestos, and size of fibers must be considered in evaluation of potential health risks.

Animals

Phagocyte enzymes in bronchoalveolar lavage from patients with pulmonary sarcoidosis and collagen vascular disorders.

The balance between proteases and antiproteases in the lower respiratory tract is believed to play a role in the outcome of interstitial lung diseases. In this cross-sectional study, we measure several phagocyte derived enzymes, namely plasminogen activator, neutrophil elastase and an ill-defined protease active on the trialanine chromophore substrate succinyl-alanine3-nitroanilide (SLAPN) in bronchoalveolar lavage (BAL) fluid from 42 patients with pulmonary sarcoidosis and from 43 patients with collagen vascular disease (CVD), 22 without lung disease (group I) and 21 associated with parenchymal lung disease (group II). The results show: a) that sarcoidosis is associated with increased plasminogen activator activity and with the presence of enzymatic activity against SLAPN corresponding at least in part to a metalloprotease; b) that CVD in the absence of radiographic lung disease is associated with an increase of plasminogen activator activity and increased levels of alpha 1-antiprotease-neutrophil elastase complexes; c) that the majority of untreated CVD (group II) patients have detectable levels of neutrophil elastase activity. These data show that patients with pulmonary sarcoidosis and CVD have different enzymatic profiles in their lower respiratory tract as assessed by BAL. Thus, sarcoidosis (mostly lymphocytic) is associated with enhanced macrophage-derived proteolytic activity in BAL, while CVD patients both with and without lung disease have increased neutrophil counts and neutrophil elastase complexed to alpha 1-protease inhibitor and presumably inactive in BAL. Finally, only BAL from untreated CVD patients with interstitial lung disease contain neutrophil elastase activity. This latter activity could contribute to the lung lesions frequently observed in these disorders.

Adult

The neutrophil, friend or foe: pharmacologic manipulation.

We describe some features of neutrophil migration and their defense or injury mechanism in the lung. Employing an intratracheal silica instillation model in rats, we examined the effects on the silica-induced neutrophil migration of mepacrine, colchicine and reserpine on such migration in vivo and of mepacrine on phorbol-stimulated elastase release and superoxide anion generation by human neutrophils in vitro. Mepacrine sharply diminished neutrophil migration, O2 and elastase release. Colchicine produced variable effects on neutrophil migration which was unaffected by the mast cell agent reserpine. The implications for lung injury and therapy are discussed.

Animals

Mepacrine impairs neutrophil response after acute lung injury in rats. Effects on neutrophil migration.

Intraalveolar leukocytosis is integral in initiating and perpetuating airspace inflammatory reactions. We used intratracheal instillation of silica suspensions in adult male rats to cause neutrophil flux (32% increase over saline controls) without creating a protein leak, so simulating an early inflammatory response. We examined the in vivo effects of a known phospholipase A2 inhibitor (mepacrine) and the two mast cell active agents (cyproheptadine and reserpine) on lung lavage fluid chemotactic capability, alveolar macrophage (AM) production of chemotactic factor(s), and neutrophil diapedesis. Only mepacrine significantly depressed the leukocytosis (from 32% to 8% of total cells), with a similar diminution in AM chemotaxin production. Separate in vitro experiments using mepacrine-pretreated neutrophils and macrophages gave evidence that mepacrine: (1) diminishes neutrophil response to chemotaxin(s), (2) inhibits spontaneous, random neutrophil movement, and (3) diminishes macrophage-derived chemotactic factor production. These observations suggest that the earliest events in alveolar inflammatory reactions probably involve local production of chemotactic factors by AM, and that mepacrine's anti-inflammatory action results from inhibitory influences on both macrophage and neutrophil populations.

Acute Disease

Asbestos exposure and laryngeal cancer: an analysis of the epidemiologic evidence.

We conducted a critical analysis of the available epidemiologic investigations on the causal relationship between asbestos exposure and laryngeal cancer. A review of nine case-control studies indicates that the estimated risk (odds ratio) attributable to asbestos exposure alone is negligible when smoking and ethanol intake are appropriately controlled for. Six of the 12 cohort studies demonstrated no significant increase in the standardized mortality ratio due to asbestos exposure. The remaining six longitudinal studies showed an increased standardized mortality ratio from 1.91 to 5.41 but no adjustment was made for the confounding effects of smoking and ethanol consumption. In conclusion, the available epidemiologic evidence does not support a causal association between asbestos exposure and laryngeal cancer.

Alcohol Drinking

Acute effect of nitrogen dioxide exposure on the functional activity of alpha-1-protease inhibitor in bronchoalveolar lavage fluid of normal subjects.

Nitrogen dioxide is one form of an oxidizing free radical that is sufficiently stable to exist in relatively high concentrations in ambient air and cigarette smoke. We examined the effect of NO2 exposure on the functional activity against pancreatic elastase of alpha-1-protease inhibitor (alpha 1PI) in bronchoalveolar lavage (BAL) fluid of nonsmoking subjects. Ten nonsmokers (mean age, 25 +/- 2 SE yr) were exposed to NO2 (3 or 4 ppm) for 3 h with intermittent exercise. Seven nonsmokers (mean age, 24 +/- 2 SE yr) underwent a similar protocol but were exposed to NO2-free air and served as control subjects. Bronchoalveolar lavage was performed 3.5 to 4 h after the end of exposure. Exposure to NO2 caused a 45% decrease in functional activity of alpha 1PI in BAL. There was no significant difference in immunoreactive alpha 1PI between the groups whether expressed as micrograms per 100 ml of recovered fluid or per milligram of albumin. This inactivation of alpha 1PI was not associated with any neutrophil migration into the air spaces of the lung. The "elastaselike" activity of BAL using synthetic elastinlike chromophore substrate succinyl-trialanine-nitroanilide showed no significant difference between the NO2-exposed group (221 +/- 39 SE ng/dl BAL) and the control group (196 +/- 61 SE ng/dl BAL). Assay for human leukocyte elastase (HLE) in concentrated BAL using the synthetic substrate Methoxysuc-Ala3-Pro-Val-aminomethylcoumarin did not detect any HLE activity in the BAL. These results showed that nonsmoking subjects exposed to relatively low concentrations of NO2 for a short time have a significant inactivation of alpha 1PI in the lower respiratory tract fluid than did nonsmoking control subjects.

Adult

Influence of sputum IgA and elastase on tracheal cell bacterial adherence.

Bacterial adherence is an important pathogenetic mechanism for airway colonization, but the influence of airway proteins on this phenomenon is largely unknown. We measured tracheal cell bacterial binding in 13 subjects with chronic tracheostomy and related these results to measurements of sputum IgA, elastase activity, and total protein from the same subjects. Tracheal cell adherence was related directly to sputum elastase activity (r = 0.61, p = 0.02); and elastase activity, primarily a serine protease, was higher in subjects colonized by Pseudomonas aeruginosa than in those without this finding (p = 0.02). Sputum levels of IgA/mg protein were related inversely to tracheal cell adherence (r = 0.64, p = 0.02). Sputum IgA concentrations, in turn, were affected by host nutritional status and airway elastase activity. Evidence that elastase can degrade sputum IgA was provided by an inverse relationship observed between these 2 proteins (r = 0.56, p = 0.04) and by in vitro mixing experiments showing fragmentation of IgA by purified neutrophil elastase. In addition, sucrose density gradient separation indicated IgA fragmentation to have occurred in vivo. These data suggest that, once adherence leads to airway colonization, the resulting inflammatory response may foster microbial growth by an elastase-dependent IgA cleavage and hence enhanced tracheal cell adherence.

Adult

An in vitro model for polymorphonuclear-leukocyte-induced injury to an extracellular matrix. Relative contribution of oxidants and elastase to fibronectin release from amnionic membranes.

Alteration of the extracellular matrix by inflammatory cells is believed to be important in both lung injury and the subsequent restoration of lung architecture. Here we describe the results of the interaction between an acellular human amnionic membrane model and stimulated human polymorphonuclear neutrophils (PMN) in vitro. Polymorphonuclear neutrophil suspensions were placed on one surface of the amnion, and either the chemotactic peptide FMLP or the cell membrane activator phorbol myristate acetate (PMA) was placed on the opposite side of the amnion. Stroma and basement membrane sides of the amnion were separately exposed to the PMN. The PMN suspension was removed and centrifuged, and the supernatant was assayed for superoxide anion (O2-.) and for elastase activity. Injury to the acellular amnion was evaluated by transmission electron microscopy and by measurement of fibronectin (FN) released from the membrane matrix. Although both stimulants cause a concentration-dependent release of O2-., only PMA stimulated elastase release. These effects were similar when either the stroma or the basement membrane side was exposed to PMN. PMA-stimulated cells and supernatants from PMA-stimulated cells caused solubilization of membrane at different incubation times. Electron microscopy confirmed the disruption of the basement membrane of the amnion by PMA-stimulated PMN. Oxidant scavengers (SOD and catalase) did not prevent matrix degradation, and elastase inhibition by a specific chloromethylketone inhibitor diminished FN release on both sides of the amnion by activated PMN supernatants, but only on the basement membrane side by intact PMN. We conclude that in this model, elastase rather than oxygen radicals solubilizes FN from the matrix.

Amnion

Vegetable dust and airway disease: inflammatory mechanisms.

Exposure to cotton or grain dust causes an obstructive bronchitis in certain subjects, mechanisms of which are poorly understood. A difficulty encountered in discerning mechanisms of this airway disease is the lack of knowledge of the active components of these dusts. Clinical features suggest common but not exact mechanisms of the airway disease associated with these vegetable dusts. Human and animal studies show evidence of acellular and cellular inflammatory mechanisms of the bronchoconstriction and inflammation associated with these disorders. Potential cellular sources include alveolar macrophages, polymorphonuclear leukocytes, mast cells, basophils, eosinophils and lymphocytes. Acellular origins include the complement and humoral antibody systems, both of which have been implicated, although their pathogenic role in grain or cotton dust disorders is uncertain. In this review we critically address potential inflammatory mechanisms of airway alterations resulting from cotton or grain dust exposure. General mechanisms of bronchoconstriction are first presented, then specific studies dealing with either of the two dusts are discussed. We believe this area of research may be fruitful in dissecting mechanisms of bronchoconstriction and airway inflammation, especially as more human studies are undertaken.

Animals

Pathophysiology and treatment of sleep apnea.

The sleep apnea syndromes have attracted the interest of physicians and scientists in many different disciplines because the disorders involve the physiology of sleep, the control of respiration, the function of the upper airway, and the clinical sequelae upon cardiac, pulmonary, and psychological function. Over the eight years since this subject was last reviewed here (1), the pathophysiology of obstructive sleep apnea has become better understood. A variety of new treatments are now available. However, our clinical knowledge of the syndrome and its natural history have changed little. The high prevalence of these syndromes and related disorders such as snoring is only beginning to be apparent. This chapter reviews current understanding of these syndromes, with particular emphasis on recent advances, and highlights questions for future investigation. First, we consider normal upper airway function and the control of breathing during sleep. Then, we apply this information to a consideration of the pathophysiology, clinical features, and treatment of sleep apnea syndromes.

Airway Resistance

A 10-year follow-up study of a group of workers exposed to isocyanates.

The ventilatory capacity of 68 workers who were exposed to isocyanates was determined. Forty-two of the workers had been studied in 1971. The overall ventilatory capacity of the subjects fell within the predicted range except that two subjects, both of whom were smokers, had minimal obstruction. No significant shift decrement was noted in any of the subjects. There was no evidence to suggest that an excess decrement in ventilatory capacity occurred during the period of observation; however, exposure to isocyanates had been well within the then-extant time-weighted average.

Adult