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Biomedical subjects

M J Utell

Publications and source records attributed to M J Utell.

At least 19 recordsLinked to original sources
PubMed1997

Retention modeling of refractory ceramic fibers (RCF) in humans.

A mathematical retention model has been developed to predict the lung burden and size distribution of kaolin refractory ceramic fibers (RCF) in the pulmonary region of the human lung during exposure. Fiber dissolution, breakage, and differential clearance are considered in this model; rates for these processes are obtained by extrapolation from available data on laboratory rats. The lung burden predicted by this model is in general agreement with fiber counts from three factory workers. An important prediction from this study is that clearance of RCF is not significantly impaired at a fiber concentration beneath 10 f/cm3 during occupational exposure.

Animals↗
PubMed1997

Determination of production of nitric oxide by lower airways of humans--theory.

Exercise and inflammatory lung disorders such as asthma and acute lung injury increase exhaled nitric oxide (NO). This finding is interpreted as a rise in production of NO by the lungs (VNO) but fails to take into account the diffusing capacity for NO (DNO) that carries NO into the pulmonary capillary blood. We have derived equations to measure VNO from the following rates, which determine NO tension in the lungs (PL) at any moment from 1) production (VNO); 2) diffusion, where DNO(PL) = rate of removal by lung capillary blood; and 3) ventilation, where V A(PL)/(PB - 47) = the rate of NO removal by alveolar ventilation (V A) and PB is barometric pressure. During open-circuit breathing when PL is not in equilibrium, d/dt PL[V(L)/ (PB - 47)] (where V(L) is volume of NO in the lower airways) = VNO - DNO(PL) - V A(PL)/(PB - 47). When PL reaches a steady state so that d/dt = 0 and V A is eliminated by rebreathing or breath holding, then PL = VNO/DNO. PL can be interpreted as NO production per unit of DNO. This equation predicts that diseases that diminish DNO but do not alter VNO will increase expired NO levels. These equations permit precise measurements of VNO that can be applied to determining factors controlling NO production by the lungs.

Air Pressure↗
PubMed1997

Ozone responsiveness in smokers and nonsmokers.

Short-term exposure to ozone causes decrements in lung function, but predictors of responsiveness remain largely unknown. Ninety healthy volunteers (56 never-smokers, age [mean +/- SD] 25 +/- 4 yr; 34 current smokers, 13 +/- 9 pack-yr, age 28 +/- 1 yr) were exposed to 0.22 ppm ozone for 4 h, with exercise, in an environmental chamber. We measured spirometry and specific airway conductance before, during, and immediately after exposure, and assessed symptoms by questionnaire. Smokers experienced a smaller increase in respiratory symptoms following exposure to ozone than did nonsmokers. Decrements in FEV1 were significantly less than for smokers than for nonsmokers (p = 0.0013). Ozone responsiveness (> 15% fall in FEV1) occurred in 16 of 56 never-smokers (28.6%) and 4 of 34 smokers (11.8%). Multiple logistic regression analysis found pack-yr of smoking to be associated with decreased ozone responsiveness (odds ratio [OR] 0.87, p = 0.017). Age, gender, and methacholine responsiveness were not predictive of responder status. Fourteen smokers and 25 nonsmokers were subsequently exposed once to air and twice to ozone; smokers as well as nonsmokers were consistent in their subsequent responsiveness (or lack of responsiveness) to ozone. Healthy smokers have smaller decrements in lung function and fewer symptoms in response to ozone exposure than do nonsmokers.

Adolescent↗
PubMed1996

Xenobiotic metabolism enzyme gene expression in human bronchial epithelial and alveolar macrophage cells.

Human bronchial epithelial cells (BEC), a primary defense against inhaled materials, are the progenitor cells for bronchogenic carcinomas and have important metabolic capabilities. We used reverse transcriptase-polymerase chain reaction (RT-PCR) to identify xenobiotic metabolism enzymes expressed in primary BEC and alveolar macrophages (AM) of non-smoking volunteers. Cytochromes P450 (CYP) 1A1, 1B1, 2B7, 2E1, and 4B1 and microsomal epoxide hydrolase (mEH) were expressed in BEC but not AM. CYP2F1 was expressed in BEC, but it was expressed at barely detectable levels or not at all in AM. NADPH oxidoreductase (NADPH OR), microsomal glutathione transferase (GST 12), glutathione transferase mu, phenol sulfotransferase (PST), thermolabile phenol sulfotransferase (TL PST), and the clara cell-specific gene, CC10 were expressed in both BEC and AM. CYP3A4 and glucuronosyl transferases-1 and 2 were not expressed in either BEC or AM. In contrast to primary BEC, of the genes evaluated, the immortalized human bronchial epithelial cell line BEP2D constitutively expressed only CYP1A1, CYP2E1, NADPH OR, glucuronosyl transferase 1, GST 12, GST mu, PST, TL PST, and CC10. The loss of xenobiotic metabolism enzyme gene expression in the BEP2D cell line may result from either reduced exposure to inducing agents, or loss of differentiative characteristics in culture. It is clear from the data comparing BEC and AM that there are important intertissue differences in expression of xenobiotic metabolism enzymes.

Base Sequence↗
PubMed1996

Human performance during exposure to toluene.

PURPOSE: The purpose of this research was to examine the effects of inhalation of toluene on respiratory function and neuropsychological performance of humans. METHODS: We exposed six healthy adults to 100 ppm toluene or air (control) for 6 h, in a double-blind, randomized fashion, with exposures separated by at least 14 d and including 30 min of exercise at a level that quadrupled minute ventilation. Blood and exhaled air toluene levels were measured before, during, immediately, and 1 and 2 h post-exposure. Lung function was measured before and immediately after exposure. Three repetitions of two computerized neuropsychological tests were performed, including a brief standard neuropsychological battery (ANAM) and a 1-h complex performance test (SYNWORK). Statistical analysis of the psychological data was conducted as a repeated measures ANOVA. FINDINGS: Following exercise, the mean blood and exhaled air toluene levels averaged 1.5 micrograms and 28 ppm, respectively. Lung function was unchanged post-exposure. On the SYNWORK test, the Composite score obtained over time during toluene exposure was lower than that during room air (F = 29.20, p = 0.005), with the score from the final hour reduced by 10%. On standard neuropsychological tests, latency but not accuracy proved the sensitive measure for five of the seven subtests presented. CONCLUSIONS: Performance of complex tests and response time to simple brief tests can be disrupted by toluene inhalation at 100 ppm. Differences in performance between air and toluene conditions were greatest after exercise, indicating that physical activity may enhance the response to volatile organic solvents.

Adult↗
PubMed1995

Sulfuric acid aerosol followed by ozone exposure in healthy and asthmatic subjects.

These studies evaluated symptom and pulmonary function responses of humans sequentially exposed to sulfuric acid aerosol and ozone. Thirty healthy subjects and 30 allergic asthmatic subjects underwent 3-hr exposures in an environmental chamber to 100 micrograms/m3 sulfuric acid and sodium chloride (control) aerosols (in random order), followed 24 hr later by 3-hr exposures to ozone (0.08, 0.12, or 0.18 ppm). Each subject was studied four times, receiving each aerosol preexposure followed by two of the three ozone concentrations. For the healthy group, no convincing symptomatic or physiologic effects of exposure to either the aerosol or ozone on lung function were found. For the asthmatic group, preexposure to sulfuric acid altered the pattern of response to ozone in comparison with sodium chloride preexposure and appeared to enhance the small mean decrements in FVC that occurred in response to 0.18 ppm ozone (means +/- SE: -3.6 +/- 1.5% with sodium chloride preexposure, -6.8 +/- 1.7% with sulfuric acid preexposure). Individual responses among asthmatic subjects were quite variable, some demonstrating reductions in FEV1 of more than 35% following ozone exposure. Analysis of variance of changes in FVC revealed evidence for interactions between aerosol and ozone exposure both immediately after (P = 0.005) and 4 hr after (P = 0.030) exposure. Similar effects were seen for FEV1. When normal and asthmatic subjects were combined, four-way analysis of variance revealed an interaction between ozone and aerosol for the entire group (P = 0.0022) and a difference between normal and asthmatic subjects (P = 0.0048). There was no significant effect of exposures on symptoms for either normal or asthmatic subjects. Asthmatic subjects differ from healthy volunteers in their functional responses following sequential exposures to aerosols and ozone and appear to represent a susceptible population.

Adult↗
PubMed1995

Environmentally induced asthma.

Asthma is characterized by inflammation, reversible airway obstruction, and increased airway responsiveness to various stimuli. Despite advances in understanding of the pathophysiology and in developing new treatments, asthma prevalence and mortality have been rising over the last decade, after a steady decline in the 1970s. Risk factors for environmentally induced asthma include air pollutants, tobacco smoke, wood smoke, and excessive allergen exposure. In controlled human chamber studies, asthmatics demonstrate increased susceptibility to outdoor pollutants such as sulfur dioxide, nitrogen dioxide, and acidic particles with acute reductions in lung function during and following exposures; responses are enhanced by increased ventilation, for example during exercise, or breathing cold air and/or dry air. The evidence is even stronger that inhaled indoor allergens have a causal relationship to asthma. It is possible that changes in housing conditions have led to increased levels of dust mite and other proteins in homes with consequent increases in the prevalence of sensitization. Avoidance of specific allergens such as house dust mite over months results in a reduction in clinical symptoms and bronchial hyperresponsiveness. The interaction between aeroallergens and air pollutants in triggering environmentally induced asthma is an area of active research.

Air Pollution↗
PubMed1995

Composition of human airway mucins and effects after inhalation of acid aerosol.

Characterization of normal airway mucus is required to elucidate mechanisms protecting the airways and to understand changes associated with disease and environmental insult. Toward this goal, we collected bronchial washes (10 ml saline) from healthy human subjects to 1) evaluate the yield of high-density material (delta > or = 1.35 g/ml), and 2) characterize glycoconjugates associated with collected secretions. Samples were lipid extracted followed by CsCl density gradient centrifugation. The yield of high-density material from individual subjects was variable but sufficient to demonstrate that mucin glycoproteins are a major constituent of mucus from healthy airways and that proteoglycans are absent. Next, we investigated whether inhalation of H2SO4 aerosol (1,000 microgram/m3), an environmental insult associated with alterations in mucociliary clearance, changes the composition of high-density glycoproteins in airway secretions. In a paired, double-blinded study, high-density fractions of bronchial secretions from 12 subjects were collected 18 h after exposures of 2 h to aerosolized NaCl and H2SO4. In all cases the high-density material displayed characteristics of mucin glycoproteins. In addition, a unique 150-kDa glycoprotein was detected in most but not all samples and may represent a small mucin glycoprotein differentially expressed in humans. No differences were noted between the two exposure conditions in the profiles of the glycoproteins or proteins after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Statistically, large changes with acid exposure in the composition of carbohydrates and amino acids were absent. Thus no substantial systematic changes in airway mucin glycoproteins or closely associated proteins and glycoproteins were correlated with H2SO4 exposure. Alternatively, statistical analysis of the differences between exposures in glycoprotein constituents among subjects denoted greater variability in carbohydrates compared with amino acids with repeated sampling, suggesting normal daily variations in the mucin composition of individual airway mucus.

Administration, Inhalation↗
PubMed1995

The acute respiratory distress syndrome: current trends in pathogenesis and management.

Management of patients in ARD remains a complex diagnostic and difficult therapeutic problem. Although the authors have focused on several new and exciting management strategies, it is important to recognize that the vast majority of patients with ARDS simply require meticulous general medical care. In this era of invasive monitoring and other care. In this era of invasive monitoring and other complex technologies, there is sometimes a tendency to neglect the basic issues such as judicious use of antibiotics to avoid superinfection with resistant organisms or antibiotic-associated diarrhea; removal of unnecessary intravenous lines to minimize line related infections; and maintenance of adequate nutrition to promote good skin and mucosal integrity as well as preserving important muscle mass all too often receive a low priority. It is anticipated that with meticulous general medical care, as well as selective implementation of the above treatment strategies, improvement in the outcome of patients is an achievable goal.

Acute Disease↗
PubMed1994

Clearance of refractory ceramic fibers (RCF) from the rat lung: development of a model.

Chronic exposure and postexposure experiments have been recently performed in rats to evaluate the biological responses of inhaled refractory ceramic fibers (RCF) at different concentration levels. The lung burden data in the accessory lobe of the rat lung were collected during and after different exposure and postexposure periods. The size distribution of retained fibers in the lung at different time points was also measured. We used these data to develop a mathematical model of fiber clearance from the rat lung. It was found that the clearance rate did not depend significantly upon fiber size but there was a clear dependence on lung burden. As lung burden increased, the clearance rate was found to decrease. An empirical equation was derived for the clearance rate as a function of lung burden. At low burdens, rats had a retention half-time of about 126 days for RCF compared to a typical half-time of about 60 days for insoluble nonfibrous particles.

Animals↗
PubMed1994

Oxidant and acid aerosol exposure in healthy subjects and subjects with asthma. Part II: Effects of sequential sulfuric acid and ozone exposures on the pulmonary function of healthy subjects and subjects with asthma.

These studies were undertaken to evaluate pulmonary responses of humans sequentially exposed to acidic aerosols and ozone at levels that could reasonably be encountered in actual environmental exposures. Subjects first were exposed to sulfuric acid (H2SO4) aerosol to sensitize the airways to ozone. The exposure protocols were designed to provide more quantitative information about the threshold levels of ozone that produce adverse biological effects and to provide exposure-response data on ozone. Two groups of 30 nonsmoking volunteers of both sexes, between the ages of 18 and 45 years, were recruited. The healthy study population comprised 16 men and 14 women with an average age of 28 years and no airway hyperreactivity. The second group comprised 10 men and 20 women comparable in age to the control group, but with allergic asthma and positive skin tests. The study examined an exposure-response relationship using three levels of ozone ranging from below the current standard to one and one-half times the ambient air quality standard (0.08, 0.12, and 0.18 ppm* [parts per million]) with preexposure 24 hours earlier to H2SO4 (100 micrograms/m3) or sodium chloride (NaCl) (control) aerosol in a 45-m3 environmental chamber. The study used an incomplete block design in which each subject was exposed to four of the six paired experimental atmospheres. Both the selection of paired exposures and the order in which they were presented were randomized. The exposure protocol required nine days: Day 1, training and baseline preexposure measurements; Day 2, the first of the three-hour particle (H2SO4 or NaCl) exposures; Day 3 (24 hours after Day 2), ozone exposure at 0.08, 0.12, or 0.18 ppm for three hours; Day 4 (two to four weeks later), exposure to the same ozone concentration as on Day 4. After at least another two weeks, Days 6, 7, 8, and 9 repeated Days 2, 3, 4, and 5 using a second ozone concentration. All three-hour exposures included several predetermined periods of exercise and pulmonary function measurements. To examine for delayed effects, pulmonary function tests were measured two and four hours after exposure on the ozone days. Data were analyzed over the time course of exposure and by exposure level of ozone at each time point to reveal dose-response relationships more closely. The main findings of the study are as follows. No significant symptomatic or physiologic effects of exposure to either aerosol or ozone on lung function were found for the healthy group.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Measurement of gene expression by multiplex competitive polymerase chain reaction.

We have developed a polymerase chain reaction (PCR)-based method to measure glutathione peroxidase (GSH-Px) mRNA levels. Expression was measured by multiplex competitive PCR amplification of (a) cDNA from GSH-Px and the "housekeeping" gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and (b) two internal standards consisting of single-base mutants of GSH-Px and GAPDH cDNA that cause either a loss (GSH-Px) or a gain (GAPDH) of an EcoRI restriction endonuclease recognition site. RNA extracted from a human papillomavirus-immortalized human bronchial epithelial cell line (BEP2D) was reverse transcribed. Serial dilutions of cDNA were PCR amplified in the presence of GSH-Px and GAPDH primers and quantified amounts of mutated internal standards. The amplified DNA was restriction digested with EcoRI and electrophoresed on an agarose gel stained with ethidium bromide, separating native from mutated products. Densitometry was performed to quantitate the bands. Our studies demonstrate that this technique measures the relative expression of GSH-Px to GAPDH precisely and reproducibly for studies done with the same master mixture and dilution of internal standards. Ratios of relative gene expression varied less than 25% from the mean. This technique will be useful to measure changes in gene expression, particularly when the amount of study sample is limited or the level of gene expression is low.

Base Sequence↗