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Biomedical subjects

J A Graham

Publications and source records attributed to J A Graham.

At least 55 records · Page 3Linked to original sources
PubMed1987

Glutathione peroxidase and glutathione transferase activity in rat lung and liver following cadmium inhalation.

A 2-h inhalation exposure to 4.6 mg Cd/m3 decreased pulmonary total glutathione peroxidase (GSH Px) activity and non-selenium peroxidase (GSH non-Se-Px) activity but had no effect on GSH selenium peroxidase (Se-Px) activity. Seventy-two hours after exposure there was an increase in total GSH Px and GSH Se-Px activity and a decrease in GSH non-Se-Px activity. Exposure to 0.44 mg Cd/m3 for 2 h caused no effect on GSH Se-Px at either 0 or 72 h post exposure, but total GSH Px and GSH non-Se-Px activities were decreased up to 72 h post exposure. Exposure to 4.6 mg Cd/m3 caused an increase in hepatic GSH Se-Px activity 72 h post exposure, but no other significant changes were observed in the liver. Changes in GSH non-Se-Px activity did not relate to changes in GSH transferase (Tr) activity. The data suggest that alterations in GSH Px activity by Cd2+ may be due to changes in GSH non-Se-Px activity and that changes in pulmonary GSH Tr and GSH non-Se-Px activities may not be as closely linked as in the liver.

Administration, Inhalation↗
PubMed1987

Evaluating the toxicity of urban patterns of oxidant gases. II. Effects in mice from chronic exposure to nitrogen dioxide.

The study reported herein evaluates the influence of a chronic exposure to an urban pattern of NO2 (continuous baseline exposure of 0.2 ppm, on which were superimposed two 1-h spikes of 0.8 ppm NO2, 5 d/wk) as compared to the baseline exposure to determine the contribution of the spikes to toxicity. Mice were exposed for up to 52 wk with interim examinations. Multivariate analysis of variance revealed a statistically significant treatment effect on infectivity (p = 0.05) and pulmonary function (p = 0.03) parameters. Infectivity mortality of mice in the spiked exposure regimen was significantly greater than that in either the NO2-background-exposed mice or in control mice. Four of the pulmonary function variables exhibited the greatest differences among the treatment groups: end expiratory volume, vital capacity, respiratory-system compliance, and multiple-breath nitrogen washout. Results from the pulmonary-function analyses indicate that the spiked exposures to 0.8 ppm NO2 may have induced a subtle lesion. The chronic study results indicate that the presence of spikes of NO2 is contributing significantly to effects on antibacterial lung defenses and pulmonary function of mice.

Administration, Inhalation↗
PubMed1987

Influence of exposure patterns of nitrogen dioxide and modifications by ozone on susceptibility to bacterial infectious disease in mice.

The nitrogen dioxide (NO2) diurnal cycle found in urban communities usually consists of a low basal concentration upon which are superimposed higher concentration peaks or spikes of short duration. Various components of this environmental exposure mode were examined to assess effects of urban exposure profiles on susceptibility to infectious pulmonary disease. Mice were exposed to NO2 peaks of 4.5 ppm for 1, 3.5, or 7 h, challenged with Streptococcus sp. either immediately or 18 h postexposure, and then observed for mortality. When the streptococcal challenges were immediately after NO2 exposure, the mortality rate was directly related to the length of peak exposure, whether or not a basal exposure was used, and all peak lengths significantly increased mortality. When the challenge was delayed for 18 h after the peak exposure, spiked exposures of 3.5 and 7 h increased mortality to the same degree. If a 1-h peak exposure to 4.5 ppm was superimposed twice daily upon a continuous basal NO2 concentration of 1.5 ppm, there was a suggestive trend toward increased mortality near the end of the second week of exposure when challenge occurred immediately after the morning spike. Studies were also conducted to examine interactions with ozone (O3) and NO2, since urban air typically contains both of these oxidants. Using various combinations of basal and spiked exposure levels of NO2 and O3, synergistic results were obtained for streptococcal-induced mortality.

Air Pollutants↗
PubMed1987

Pulmonary effects due to short-term exposure to oil fog.

Rats were exposed to an oil fog generated by flash vaporation and subsequent condensation of lightweight lubricating oil. Exposures were for 3.5 h/d, 4 d/wk, for 4 wk, at concentrations of 1.5, 0.5, or 0.0 mg/l and a particle size of approximately 1 micron. Samples of respiratory tissues were taken for histopathologic analyses, lavage fluid samples were collected, and pulmonary function measurements were made the day after the last exposure. An accumulation of macrophages within the alveolar lumen, an increase in lavage fluid protein content, and an increase in total cell content in lavage fluid due to an influx of polymorphonuclear leukocytes was noted in rats exposed at the 1.5-mg level. Also, for this exposure group there was an increase in lung wet and dry weight and an increase in end-expiratory volume, and pneumonitis was observed histopathologically in 4 of 10 male rats exposed. Pneumonitis was not observed among six female rats examined. Oil fog had no effect on total lung capacity, residual volume, vital capacity, lung compliance, or the distribution of ventilated air within the lung. Effects following exposure to 0.5 mg/l were limited to slight accumulation of macrophages in the alveolar lumen and an increase in the total cells in lavage fluid, which could not be attributed to an increase in any particular cell type.

Air Pollutants↗
PubMed1987

A comparative study of the effects of inhaled cadmium chloride and cadmium oxide: pulmonary response.

The effects of aerosols of cadmium chloride (CdCl2) and cadmium oxide (CdO) on pulmonary biochemical function were compared. Rats and rabbits were exposed to 0.25, 0.45, or 4.5 mg Cd/m3 for 2 h. Pulmonary toxicity was determined histologically and biochemically. Cadmium chloride and CdO showed a deposition response that was linearly related to the chamber concentration. Both compounds caused multifocal, interstitial pneumonitis 72 h after exposure, but the CdO lesion was more severe with proliferation of fibrocytic-like cells as well as pneumocytes. Comparing the two Cd compounds at the highest concentration (4.5 mg Cd/m3), the biochemical responses in the rat were similar. The majority of the effects occurred 72 h after exposure, with significant increases in lung weight, lung-to-body weight ratio, GSH reductase, GSH transferase, and G-6-PDH. However, GSH peroxidase was inhibited immediately after the CdO exposure. Cadmium oxide-related alterations in the parameters studied could easily be distinguished from those of CdCl2 at the exposure concentration of 0.45 mg Cd/m3. The response pattern in the rabbit resembled that of the rat. In both species Cd had a consistent inhibitory effect on pulmonary GSH peroxidase, even at the lowest concentration of 0.25 mg Cd/m3. Based on these findings, inhaled CdO appeared to be more toxic to the lung than inhaled CdCl2.

Aerosols↗
PubMed1987

Poly(I):poly(C)-enhanced alveolar and peritoneal macrophage phagocytosis: quantification by a new method utilizing fluorescent beads.

Phagocytosis is an important immune function to quantify. This immune response may be modulated by exposure to biological response modifiers or by exposure to pollutants. A new technique for quantifying nonspecific phagocytosis of alveolar and peritoneal macrophages in the same animal has been developed that utilizes fluorescent polystyrene beads. When incorporated into inhalation studies, this technique can be used to determine whether the toxic effect of an inhaled pollutant is local (effect on alveolar macrophages), systemic (effect on peritoneal macrophages), or both local and systemic. This method results in a determination of both the level of phagocytosis (the percentage of phagocytic macrophages) and the macrophage specific activity (the number of beads phagocytized per macrophage). This method also allows a determination of adherence by quantifying the number of particles in contact with, but not phagocytized by, the macrophage. Macrophage preparations were incubated with fluorescent beads for 2 hr and cyto-centrifuged onto a glass slide. Fluorescent beads present on the slide or cell-associated but not ingested by phagocytosis were removed by immersing the slide containing the macrophage preparation in methylene chloride for 15-30 sec. Fluorescent beads ingested by phagocytosis were then easily quantified with a fluorescence microscope. This technique was used to assess the baseline levels of phagocytosis for rat alveolar and peritoneal macrophages from the same animal and the kinetics and level of enhanced phagocytosis for alveolar and peritoneal macrophages after injection with the interferon inducer polyinosinate-polycytidylate (poly(I):poly(C)). The kinetics of enhanced alveolar and peritoneal macrophage phagocytosis by poly(I):poly(C) were similar; however, stimulated phagocytic levels of peritoneal macrophages never reached the phagocytic activity observed for the resident, highly phagocytic alveolar macrophages. This elevated phagocytic activity is most likely due to interferon stimulated by particulate matter in the large volume of air processed by the lungs and is important for host defense against a number of different inhaled microorganisms.

Animals↗
PubMed1986

Effects of subchronic inhalation of low concentrations of nitrogen dioxide. I. The proximal alveolar region of juvenile and adult rats.

Inhalation of nitrogen dioxide (NO2) produces injury to the epithelium of terminal airways and the alveoli proximal to the airways. Techniques were devised to isolate alveolar tissue from this region for morphometric studies to define the extent of alveolar septal injury caused by NO2. One-day-old and six-week-old rats were exposed to either room air or 0.5 ppm NO2 for 23 hr per day 7 days per week for 6 weeks. An additional group of 6-week-old rats were exposed to 2.0 ppm NO2 for the same duration. Two daily hour spikes to three times the background concentrations (0.5 to 1.5 ppm and 2.0 to 6.0 ppm) were applied Monday through Friday. At the end of the exposure, rat lungs were fixed by intratracheally infusing buffered 2% glutaraldehyde. Pieces of lung tissue were embedded in large plastic blocks which were softened with heat and thin (0.3 mm) sliced. Terminal bronchioles and their corresponding proximal alveolar regions were identified from the thin plastic slices, removed, and glued to cylindrical EM blocks for thin sectioning. Morphometric analysis revealed that epithelial injury occurred in all exposed animals. The juvenile rats which had been exposed to 0.5 ppm NO2 since 1 day of age exhibited changes in the characteristics of type II epithelial cells. These cells spread to cover more alveolar surface and became thinner. Adult animals exposed to 0.5 and 2.0 ppm NO2 showed changes in alveolar macrophages and in the alveolar interstitium in addition to changes in the epithelium. Animals exposed to 0.5 ppm NO2 showed spreading and hypertrophy of type II epithelial cells. Those animals exposed to the higher concentration of NO2 had similar changes in type II epithelial cells and in addition showed an increase in type I cell number. The type I epithelial cells were smaller and covered less alveolar surface area than normal type I cells, suggesting a regenerating population of type I cells. These results suggest that prolonged exposure to low concentrations of NO2 can cause injury to the alveolar epithelium indicated initially by spreading and hypertrophy of type II cells followed by differentiation into type I cells to compensate and repair the injury. Adult rats were as sensitive or more sensitive to NO2 injury than were juvenile rats.

Aging↗
PubMed1986

The effects of inhalation of organic chemical air contaminants on murine lung host defenses.

The potential health hazards of exposure to threshold limit value (TLV) concentrations of acetaldehyde, acrolein, propylene oxide, chloroform, methyl chloroform, carbon tetrachloride, allyl chloride, methylene chloride, ethylene trichloride, perchloroethylene, benzene, phenol, monochlorobenzene, and benzyl chloride, compounds which may be present in the ambient or work room atmosphere were investigated. The effects of single and multiple 3-hr inhalation exposures were evaluated in mice by monitoring changes in their susceptibility to experimentally induced streptococcus aerosol infection and pulmonary bactericidal activity to inhaled Klebsiella pneumoniae. When significant changes in these parameters were found, further exposures were performed at reduced vapor concentrations until the no-measurable-effect level was reached. Multiple exposures on 5 consecutive days were then performed at this concentration. Significant increases in susceptibility to respiratory streptococcus infection were observed after single 3-hr exposure to TLV concentrations of methylene chloride, perchloroethylene, and ethylene trichloride. For methylene chloride and perchloroethylene, these exposure conditions also resulted in significantly decreased pulmonary bactericidal activity.

Air Pollutants↗
PubMed1986

A perinatal study of toluene in CD-1 mice.

Toluene administered by inhalation at 400 ppm to CD-1 mice from Days 6 to 16 of gestation was teratogenic but not fetotoxic resulting in a significant shift in the fetal rib profile. At the lower concentration of 200 ppm, there was an increase in dilated renal pelves which might reflect desynchronization of maturation with respect to development and growth. No other effects were noted at the 200-ppm concentration. At 400 ppm, toluene also produced an increased body weight in the neonates on Day 1 postpartum following in utero exposure. Activity of lactic dehydrogenase (LDH) was significantly increased in the brains of dams exposed to 400 ppm during gestation while nonpregnant adult mice studied concurrently had significant increased activities of LDH in the liver and kidneys of the 400-ppm group. The only change in the isozyme profiles was in the kidneys of the nonpregnant adult mice in which a slight decrease in LDH-2 was observed. No other changes were noted in the dams or pups.

Abnormalities, Drug-Induced↗
PubMed1986

Effects of ammonium nitrate aerosol exposure on lung structure of normal and elastase-impaired rats and guinea pigs.

Groups of rats and guinea pigs with normal lungs and others with elastase-induced emphysema were exposed to NH4NO3 aerosols of 0.60 mass median aerodynamic diameter at 1 mg/m3 for 6 hr/day, 5 days/week, for 4 weeks. Morphologic and morphometric studies were performed on lungs perfused with cacodylate-buffered 2% glutaraldehyde under 20 cm H2O pressure at necropsy. The tissues were studied for pathologic change by light and electron microscopy; emphysema was evaluated by subgross and microscopic methods, including changes in mean alveolar chord length using scanning electron microscopy techniques. Elastase produced emphysema to a degree quantifiable by all criteria studied; however, it apparently obscured the effects of nitrate inhalation. The NH4NO3 exposure (compared to air alone) tended to increase values for pulmonary parameters in normal animals of both species and to decrease them in elastase-treated animals. The NH4NO3 exposure increased values for lung volume in rats, percentage area affected in elastase-treated rats, and chord length beta in normal animals of both species. The responses to NH4NO3 were slight (P less than 0.10) and were not accompanied by any detectable changes in alveolar structure. Therefore, the effects of NH4NO3 at this exposure level and duration, are regarded as biologically insignificant for rats and guinea pigs.

Aerosols↗
PubMed1986

Comparative study of various methods used for determining health effects of inhaled sulfates.

Various health effect parameters were compared to determine which tests were the most sensitive indicators of toxic effects of exposure to metallic sulfate aerosols. Inhalation studies were conducted involving either single 3-hr exposure to various concentrations of cupric sulfate (0.43-2.64 mg/m3 SO4), aluminum sulfate (1.65-2.75 mg/m3 SO4), and aluminum ammonium sulfate (1.47-3.81 mg/m3 SO4) or multiple (five and ten) daily 3-hr exposures to cupric sulfate (0.1 mg/m3 SO4). The test parameters studied in male and female CD1 mice were changes in mortality after respiratory infection with Group C Streptococcus zooepidemicus; pulmonary bactericidal activity; pulmonary cell number, type, viability, and ATP content; and pulmonary morphology by scanning electron microscopy. Tracheal ciliary beating frequency and morphology were also studied in both CD1 mice and Syrian golden hamsters. Differences in bacteria-induced mortality rate appeared to be the most sensitive and consistent indicators of pollutant damage. The other parameters produced evidence of damage but generally only at the higher pollutant concentrations. Cupric sulfate was the most toxic of the three sulfates, but the differences between the toxicity of the aluminum sulfate and aluminum ammonium sulfate were less clear.

Adenosine Triphosphate↗
PubMed1986

Species comparison of acute inhalation toxicity of ozone and phosgene.

A comparison of the concentration-response effects of inhaled ozone (O3) and phosgene (COCl2) in different species of laboratory animals was made in order to better understand the influence of the choice of species in inhalation toxicity studies. The effect of 4-h exposures to ozone at concentrations of 0.2, 0.5, 1.0, and 2.0 ppm, and to COCl2 and 0.1, 0.2, 0.5, and 1.0 ppm was determined in rabbits, guinea pigs, rats, hamsters, and mice. Lavage fluid protein (LFP) accumulation 18-20 h after exposure was used as the indicator of O3- and COCl2-induced pulmonary edema. All species had similar basal levels of LFP (250-350 mg/ml) when a volume of saline that approximated the total lung capacity was used to lavage the collapsed lungs. Ozone effects were most marked in guinea pigs, which showed significant effects at 0.2 ppm and above. Mice, hamsters, and rats showed effects at 1.0 ppm O3 and above, while rabbits responded only at 2.0 ppm O3. Phosgene similarly affected mice, hamsters, and rats at 0.2 ppm and above, while guinea pigs and rabbits were affected at 0.5 ppm and above. Percent recovery of lavage fluid varied significantly between species, guinea pigs having lower recovery than other species with both gases. Lavage fluid recovery was lower following exposure to higher levels of O3 but not COCl2. Results of this study indicate that significant species differences are seen in the response to low levels of O3 and COCl2. These differences do not appear to be related in a simple manner to body weight.

Animals↗
PubMed1986

The psychology of appearance in the elderly.

Appearance counts heavily in human affairs. The good-looking have many advantages. These benefits also extend to old age. Elderly persons who preserve a youthful appearance (look young for their age) are likely to be more optimistic, more outgoing, and more social. They rate themselves more highly on many psychologic dimensions. Those who look older than their stated age die earlier and are not as healthy physiologically. Cosmetics can help the elderly attain some of the benefits enjoyed by the physically attractive.

Aged↗
PubMed1985

Effect of ozone on serum lipids and lipoproteins in the rat.

Exposure of male rats to 0 (air), 1, 1.75, and 3 ppm ozone (O3) 5 hr/day for a total of 10 days resulted in a positive linear relationship between ozone concentration and the concentrations of serum total lipoprotein free cholesterol (FCh) and high-density lipoprotein total cholesterol (HDL-Ch). The latter response was reflected in both its free (HDL-FCh) and esterified (HDL-ChE) components. On the other hand, serum triglycerides (TG) showed a marked decreasing linear trend with increasing ozone concentration. As judged by decreased body weights with no accompanying differences in feed consumption, apparent metabolic rate increased as ozone concentration increased. In another experiment, male rats were exposed 5 hr/day to either air or 1 ppm O3 for a total of 15 days. Groups of animals from each exposure were sampled at times ranging from immediately after to 44 hr postexposure. In agreement with the concentration response study, effects of O3 included increases in serum total cholesterol (Ch), HDL-Ch and HDL-FCh, and a decrease in TG. In addition, the degree of effects appeared to be maintained over the 44-hr period and to be greater than that observed at 1 ppm O3 in the concentration-response study.

Animals↗
PubMed1985

Inhalable particles and pulmonary host defense: in vivo and in vitro effects of ambient air and combustion particles.

The ability of particulate air pollutants (and possible constituents) to alter pulmonary host defenses was examined using an in vitro alveolar macrophage cytotoxicity assay and an in vivo bacterial infectivity screening test which employed intratracheal injection of the particles. A wide range of response between particles was seen at the 1.0-mg/ml level in vitro and the 0.1-mg/mouse level in vivo. A sample of fluidized-bed coal fly ash, bentonite, asbestos, some ambient air particles, and heavy metal oxides greatly increased susceptibility to pulmonary bacterial infection. Most coal fly ash samples and some air particles caused moderate increases in infectivity, while diesel particulates, volcanic ash, and crystalline silica caused only small increases. Cytotoxic effects on macrophages in vitro were observed with most of the particles. The in vivo and in vitro assays produced a similar ranking of toxicity; however, not all particles that were highly cytotoxic were potent in increasing bacterial infectivity. Increased toxicity measurable by either assay often appeared to be associated with small size or with the presence of metal in the particles.

Air Pollutants↗
PubMed1985

Inhalation studies of Mt. St. Helens volcanic ash in animals. I. Introduction and exposure system.

Due to the lack of information on the effects of inhaled Mt. St. Helens volcanic ash and its potential interaction with sulfur dioxide (SO2), animal studies were performed to determine the acute and chronic health effects of a short-term exposure. This paper describes the inhalation exposure system designed for these studies and theoretically compares the pulmonary deposition in the rats to that in humans. Considering the similarities and differences in regional pulmonary deposition in humans and animals, inhalation studies were performed with fine-mode (less than 2.5 micron aerodynamic diameter, Dae) ash. Comparisons to coarse-mode (greater than 2.5 micron Dae) ash were made using intratracheal instillation. A whole-body exposure system was designed to provide inhalation exposures of animals to Mt. St. Helens volcanic ash, SO2, or a combination of both. All exposures were conducted using fine-mode ash samples generated by a Wright dust feed mechanism at a mean concentration of 9.4 mg/m3 +/- 1.0 SD. Sulfur dioxide was maintained at 2.5 mg/m3 +/- 0.13 SD. Scanning electron microscopy, X-ray diffraction, and X-ray fluorescence were used to characterize the ash.

Air Pollutants↗