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Biomedical subjects

J B Gee

Publications and source records attributed to J B Gee.

At least 37 records · Page 2Linked to original sources
PubMed1988

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

Demonstration of a free elastolytic metalloenzyme in human lung lavage fluid and its relationship to alpha 1-antiprotease.

Although the human alveolar macrophage in tissue culture can secrete an elastolytic metalloenzyme that is not inactivated by alpha 1-antiprotease (AAP), levels of this proteolytic activity and its relationship to AAP in human lung lavage fluid ( HLF ) are unknown from previous studies. Therefore, we measured elastolytic activity in concentrated (20- to 30-fold) HLF from 15 smokers and 10 nonsmokers and related results to measurements of AAP in these fluids. Activity (mean +/- SEM) against a C elastin substrate (expressed as nanograms of porcine pancreatic elastase equivalents per milligram of lavage fluid protein) in smokers, 18.9 +/- 6.7, significantly exceeded (p = 0.05) levels present in nonsmokers, 4.4 +/- 1.8. With the synthetic elastin-like chromophore substrate succinyl-trialanine-nitroanilide ( SLAPN ), activity in individual samples was reduced 79% by EDTA, a metalloproteinase inhibitor, whereas activity was reduced by only 29% in the presence of PMSF, a serine proteinase inhibitor. In addition, using a pooled sample of HLF and C elastin substrate, 80% of activity against the elastin substrate was eliminated by EDTA, whereas 51% was eliminated by PMSF. The activity measured with C elastin substrate correlated inversely with antigenic AAP (r = -0.05, p = 0.01), but no correlations were found between this activity and HLF cell number, cell viability, differential count, or subject smoking history. The detection of activity with C elastin in HLF , with primarily a metalloenzyme inhibitor profile, in the presence of antigenically detectable AAP, may have pathogenetic relevance for emphysema in humans.

Adult↗
PubMed1984

Effects of a series of chloromethyl ketone protease inhibitors on superoxide release and the glutathione system in human polymorphonuclear leukocytes and alveolar macrophages.

Certain chloromethyl ketone (CH2Cl) protease inhibitors diminish PMA-stimulated (phorbol myristate acetate) superoxide (O-2) release by both human alveolar macrophages (HAM) and polymorphonuclear leukocytes (PMN). Additionally, these compounds diminish glutathione reductase activity (GSSR) and intracellular levels of reduced glutathione (GSH). Inhibitory profiles of these molecules were similar for each of the measured cell products, i.e., TPCK = Z Gly-Leu-Phe-CH2Cl greater than TLCK greater than Meo Succ-(Ala)2-Pro-Val-CH2Cl. Because Meo Succ-(Ala)2-Pro-Val inhibited GSSR in cell sonicates but not in intact cells, it appears that all these effects are closely related to the cell penetration by these CH2Cl compounds. We conclude that (1) inhibition of O-2 release in PMN and HAM by CH2Cl does not necessarily implicate a surface protease in O-2 production, (2) some of these compounds certainly impair the intracellular glutathione redox system necessary for the respiratory burst, and (3) only the nonpenetrating inhibitor Meo Succ-(Ala)2-Pro-Val-CH2Cl can be used to distinguish injury caused by extracellular protease (elastase) from that caused by superoxide anion.

Amino Acid Chloromethyl Ketones↗
PubMed1984

Proteins of the cystic fibrosis respiratory tract. Fragmented immunoglobulin G opsonic antibody causing defective opsonophagocytosis.

In the disease cystic fibrosis (CF), pulmonary infection with Pseudomonas aeruginosa is a common clinical complication that determines most morbidity and almost all excess mortality. We postulated that in this disease a defect in Pseudomonas-reactive IgG antibodies may contribute to chronic Pseudomonas infections. Bronchoalveolar lavages were performed upon 13 patients with CF, 7 patients with chronic bronchitis characterized by recurrent Pseudomonas infections, and 4 normal volunteers. The levels of various proteins important to host defenses and proteases were determined; enzyme inhibition studies were performed. CF respiratory immunoglobulin levels were significantly elevated when compared with both normals and patients with chronic bronchitis (P less than 0.05). Albumin and transferrin levels were decreased in the CF lung fluids. CF elastolytic activity was strikingly elevated (means = 6.02 micrograms/mg total protein) and the inhibitory profile suggested such activity resembled a serine-proteinase. Alpha-1-antitrypsin antigenic levels were not altered in CF respiratory fluids. There was a tendency for the lavage IgG to fall as elastase levels rose (r = -0.29). IgG opsonins for two Pseudomonas immunotypes were isolated with affinity chromatography for functional and immunochemical studies. Bacterial phagocytic rates in the presence of these Pseudomonas-reactive IgG opsonins derived from CF lavage fluid were depressed (0.3% uptake/unit time) when compared with similarly titered positive controls (uptake = 1.3%/unit time, P less than 0.001). Additionally, normal pulmonary macrophage intracellular killing of Pseudomonas was severely altered in the presence of opsonins derived from CF respiratory fluids. At some time points, less than 30% of the bacteria were killed. CF IgG opsonins contain a cleavage fragment (100,000 D, 5S sedimentation coefficient) with antigenic determinants similar to the Fab portion of IgG. The presence of such a fragment was inversely correlated with phagocytic functional activity. Intact IgG comprised as little as 18% of the CF lavage fluid specimens. Aliquots of intact human IgG, when mixed with the CF opsonins, augmented Pseudomonas uptake and improved intracellular killing. Conversely, peptide fragments of IgG opsonins, which are proteolytically derived in vitro, duplicated in our system the defect observed with opsonins derived from CF lung fluids; bacterial uptake was inversely related to the concentration of F(ab')2 and to a greater degree, to Fc present in the opsonic mixture. We concluded that IgG respiratory opsonins are fragmented, inhibiting phagocytosis and serving a permissive role in the chronic Pseudomonas pulmonary infection in the disease CF.

Adult↗
PubMed1984

Progressive immune failure in dyskeratosis congenita. Report of an adult in whom Pneumocystis carinii and fatal disseminated candidiasis developed.

Community-acquired Pneumocystis carinii pneumonia developed in a young adult patient with dyskeratosis congenita. His hospitalization ended fatally with disseminated candidiasis. Evaluation during the admission showed evidence of cellular immune dysfunction as indicated by skin test anergy and absent lymphocyte proliferation in an in vitro mixed lymphocyte culture. Treatment with transfer factor failed to reverse the cutaneous anergy or affect the clinical course. Dyskeratosis congenita is a rare multisystem disorder with prominent dermatologic manifestations; bone marrow failure or malignant neoplasm are common fatal outcomes. Immune system abnormalities are not classically considered a part of the disease complex. Serial evaluation of our patient's condition over several years suggests that depressed immune function, especially of the cellular limb, may evolve as a feature of clinical importance in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Exercise testing in occupational lung diseases.

The authors discuss the value of exercise testing in two areas of importance in occupational pulmonary disease: (1) the surveillance of worker populations in order to gain epidemiologic and physiologic understanding of disease and (2) the assessment of work capacity in individual patients.

Asbestosis↗
PubMed1981

Effect of SQ 14225, an inhibitor of angiotensin I-converting enzyme, on the granulomatous response to Schistosoma mansoni eggs in mice.

Murine schistosomiasis is a granulomatous disease associated with high serum and granuloma angiotensin I-converting enzyme (ACE) activity. SQ 14225, a specific competitive inhibitor of ACE, was administered to normal mice and mice infected with Schistosoma mansoni to determine whether this compound could inhibit granuloma ACE activity and modify the size of the granulomatous response to schistosome eggs. Peroral administration of SQ 14225 for 5 wk to infected mice with peak granulomatous responses decreased ACE activity in isolated liver granulomas. Treated mice demonstrated a decrease in granuloma size in the liver, colon, and ileum, and hydroxyproline concentration of isolated liver granulomas was increased. Mean diameters of synchronous pulmonary granulomas, induced by the pulmonary embolization of schistosome eggs into normal and sensitized mice, were decreased by a similar dose of SQ 14225. Withdrawal of SQ 14225 from unsensitized mice with 2-wk-old synchronous pulmonary granulomas induced an increase in inflammation. Infected, but not normal mice receiving SQ 14225 demonstrated reduced portal pressure, liver weight, and body weight. Both normal and infected mice experienced dipsogenesis, expanded intravascular volume, and increased serum ACE. These observations suggest that SQ 14225 can partially inhibit the granulomatous response to schistosome eggs and the pathological manifestations of schistosomiasis. It is possible that ACE has an inflammatory role in granulomatous inflammation.

Angiotensin-Converting Enzyme Inhibitors↗