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Terry Gordon

Publications and source records attributed to Terry Gordon.

25 records · Page 2Linked to original sources
PubMed2002

Lung-specific expression of dominant-negative mutant p53 in transgenic mice increases spontaneous and benzo(a)pyrene-induced lung cancer.

Mutations in the p53 gene have been implicated to play an important role in the development of various human cancers. To evaluate the importance of p53 in lung cancer, a transgenic mouse model was established by utilizing the Clara cell secretory protein (CCSP) promoter to target the expression of a dominant-negative mutant form of p53 (dnp53) in the lung. In two transgenic CCSP-dnp53 founder lines, the dnp53 protein was expressed exclusively in the lungs. The incidence of spontaneous lung cancer in 18-month-old transgenic mice was 45%, whereas that in age-matched control mice was 20%. The relative risk of lung tumors in CCSP-dnp53 mice was 2.3 times that of wild-type mice (exact confidence limits of 0.69, 17.5). In addition to the increased incidence of spontaneous lung tumor, these mice were more susceptible to the development of lung adenocarcinoma after exposure to benzo(a)pyrene (BaP). Six months after intratracheal instillation of benzo(a)pyrene, the tumor incidence in wild-type and CCSP-dnp53 mice was 39% and 73%, respectively. The risk of lung tumors was 25.3 times greater in BaP-treated mice adjusted for transgene expression (95% confidence limits of 3.29, 678, mid-p corrected). These results suggest that p53 function is important for protecting mice from both spontaneous and BaP-induced lung cancers.

Adenocarcinoma↗
PubMed2002

Size fractions of ambient particulate matter induce granulocyte macrophage colony-stimulating factor in human bronchial epithelial cells by mitogen-activated protein kinase pathways.

Environmental pollutants, including ambient particulate matter (PM), increase respiratory morbidity. Studies of model PM particles, including residual oil fly ash and freshly generated diesel exhaust particles, have demonstrated that PM affects inflammatory airway responses. Neither of these particles completely represents ambient PM, and therefore questions remain about ambient particulates. We hypothesized that ambient PM of different size fractions collected from an urban environment (New York City air), would activate primary culture human bronchial epithelial cells (HBECs). Because of the importance of granulocyte-macrophage colony-stimulating factor (GM-CSF) on inflammatory and immunomodulatory processes, we focused our studies on this cytokine. We demonstrated that the smallest size fraction (ultrafine/fine; < 0.18 micro m) of ambient PM (11 micro g/cm(2)), upregulated GM-CSF production (2-fold increase). The absence of effect of carbon particles of similar size, and the day-to-day variation in response, suggested that the chemical composition, but not the particle itself, was necessary for GM-CSF induction. Activation of the extracellular signal-regulated kinase and the p38 mitogen-activated protein kinase was associated with, and necessary for, GM-CSF release. These studies serve to corroborate and extend those on model particles. Moreover, they emphasize the role of the smallest size ambient particles in airway epithelial cell responses.

Air Pollutants↗
PubMed2002

Quantitative analysis of cardiac data from rats monitored by telemetry: reducing within- and between-animal variability.

Few studies have examined the sources of variability in cardiac function measurements in unrestrained animals and the impact of this variability on detection of treatment effects. The heart rate was monitored with implanted ECG transmitters in two groups of male rats, age 7 and 23 mo. Animals were monitored in their cages to determine optimal heart rate sampling frequency and sources of variability in heart rate, including whether there were persistent animal-to-animal differences. Ambient temperature was transiently increased to test whether correction for animal-to-animal differences improved sensitivity for detection of treatment effects. Animal-to-animal differences were statistically significant and accounted for about 18.3% and 11.5% of the total variance for old and young rats, respectively. In both the old and young rats, the heart rate decreased during the heat challenges relative to the control group, but the noncorrected differences were not statistically significant. When pre-exposure baseline values for each rat (average of 72 h prior to the first temperature challenge) were subtracted, the decrease in heart rate was statistically significant during all three challenges for both old and young rats. Subtraction of preexposure heart rate data to correct for baseline differences between animals is important for measuring treatment effects.

Age Factors↗
PubMed2002

Second inter-laboratory study comparing endotoxin assay results from cotton dust.

Previously, a large two-part inter-laboratory round robin endotoxin assay study was completed. This first study showed that when cotton dust samples, which are practically identical, are assayed for endotoxin that the intra- laboratory results had a very small variation while intra-laboratory results of the sample had a very high variation. In the first part of the study, each laboratory followed its own in-house assay protocol; but in the second part of the study, when the extraction protocol was standardized, the inter-laboratory results showed a lower variation, which suggested that with further standardization, further reduction of differences between laboratories might be achieved in order that results between laboratories would become more comparable. The results stimulated interest in extending the study to include cotton dust with two levels of endotoxin, standardization of the extraction protocol, and using the same assay kit from the same production lot. The results of this second round robin endotoxin assay study indicate that differences between laboratories are still high, but most of the laboratories could discern the cotton dusts with the different levels of endotoxin.

Chemistry Techniques, Analytical↗
PubMed2002

Ozone-induced modulation of airway hyperresponsiveness in guinea pigs.

Although acute exposure to ozone (03*) has been shown to influence the severity and prevalence of airway hyperresponsiveness, information has been lacking on effects due to long-term exposure at relatively low exposure concentrations. The goals of this study were to determine whether long-term repeated ozone exposures could induce nonspecific hyperresponsiveness in normal, nonatopic (nonsensitized) animals, whether such exposure could exacerbate the preexisting hyperresponsive state in atopic (sensitized) animals, or both. The study was also designed to determine whether gender modulated airway responsiveness related to ozone exposure. Airway responsiveness was measured during and after exposure to 0.1 and 0.3 ppm ozone for 4 hours/day, 4 days/week for 24 weeks in normal, nonsensitized guinea pigs, in guinea pigs sensitized to an allergen (ovalbumin) prior to initiation of ozone exposures, and in animals sensitized concurrently with ozone exposures. Both male and female animals were studied. Ozone exposure did not produce airway hyperresponsiveness in nonsensitized animals. Ozone exposure did exacerbate airway hyperresponsiveness to specific and nonspecific bronchoprovocation in both groups of sensitized animals, and this effect persisted at least 4 weeks after the end of the exposures. Although the overall degree of airway responsiveness did differ between genders (males had more responsive airways than did females), the airway response to ozone exposure did not differ between the two groups. Ozone-induced effects upon airway responsiveness were not associated with the number of pulmonary eosinophils or with any chronic pulmonary inflammatory response. Levels of antigen-specific antibodies increased in sensitized animals, and a significant correlation was observed between airway responsiveness and antibody levels. The results of this study provide support for a role of ambient ozone exposure in exacerbation of airway dysfunction in persons with atopy.

Acute Disease↗
PubMedDate not supplied

Exposure to wood dust and heavy metals in workers using CCA pressure-treated wood.

Chemical pesticide treatment enables relatively nonresistant woods to be used in outdoor construction projects. The most prevalent procedure used to protect these woods is pressure treatment with chromium, copper, and arsenic (CCA). This pilot study examined the airborne concentration and particle size distribution of wood particles, chromium, copper, and arsenic at both outdoor (measured over the whole work day) and indoor (measured during the performance of specific tasks) work sites. At the outdoor residential deck construction sites, the arithmetic mean total dust concentration, measured using personal filter cassette samplers, was 0.57 mg/m3. The mass median aerodynamic diameter (da) of the outdoor wood dust was greater than 20 microm. Indoor wood dust concentrations were significantly greater than those measured outdoor and were job category-dependent. The highest mean breathing zone dust concentration, 49.0 mg/m3, was measured at the indoor sanding operation. Personal impactor sampling demonstrated that the mean total airborne concentration of arsenic, but not chromium or copper, was consistently above recommended occupational exposure levels at the indoor work site, and occasionally at the outdoor work sites. At the indoor sanding operation, the mean total chromium, copper, and arsenic concentrations were 345, 170, and 342 microg/m3, respectively. Thus, significant exposure to airborne heavy metals can occur as a result of indoor and outdoor exposure to CCA pressure-treated wood dust. Therefore, current standards for wood dust may not adequately protect workers from the heavy metals commonly used in CCA pressure-treated wood.

Air Pollutants↗