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Biomedical subjects

J A Graham

Publications and source records attributed to J A Graham.

At least 91 records · Page 5Linked to original sources
PubMed1982

Pulmonary host defense responses to inhalation of sulfuric acid and ozone.

The effects of simultaneous exposure to ozone (O3) and sulfuric acid [H2SO4, 0.23 microns volume median diameter (VMD)] and a single exposure to ultrafine (less than 0.1 micron VMD) H2SO4 under various conditions were studied using the infectivity/mortality and the ciliary beating frequency model systems. A 3-h exposure to a combined aerosol of 196 micrograms O3/m3 and 483 or 241 micrograms H2SO4/m3 significantly increased the susceptibility of mice to a laboratory-induced respiratory infection. However, exposure to 543 micrograms ultrafine H2SO4/m3 for 2 h or 365 micrograms/m3 2 h/d for 5 d did not significantly affect this parameter. Upper airway response, as measured by changes in hamster tracheal ciliary beating frequency, was not affected by either a 3-h combined exposure to 196 micrograms O3/m3 and 847 micrograms H2SO4/m3 or a 2-h exposure to 458 micrograms ultrafine H2SO4/m3.

Aerosols↗
PubMed1982

Effects of immunosuppression with cyclophosphamide on acute murine cytomegalovirus infection and virus-augmented natural killer cell activity.

The effects of cyclophosphamide (CY) treatment on acute murine cytomegalovirus (MCMV) infection were studied to explore the potential usefulness of MCMV as a means of detecting immune dysfunction and to identify host defense mechanisms important for protection against MCMV. Conditions found optimal for enhancing MCMV infection with CY included infecting adult mice with 2 X 10(5) PFU or more of virus and administering 80 mg or more of CY per kg 1 to 3 days later. In addition to enhanced mortality, virus titers in lung, liver, and spleen were elevated in CY-treated mice, and wet weights of liver, spleen, and thymus were depressed when compared with those of infected but untreated mice. Treatment with CY before MCMV challenge was not as efficient a means of enhancing mortality as treatment after virus challenge. The effect that the time of CY administration relative to infection had on mortality correlated with the effect of such timing on natural killer cell activity. Animals treated before infection exhibited depressed natural killer cell activity initially. However, they rapidly recovered this response, and by 5 days postinfection they had the same level of virus-augmented activity seen in untreated mice. In contrast, animals treated after infection did not recover natural killer cell activity and were more likely to die. A similar correlation was not obtained when the effects of CY on lymphocyte responses to B and T cell mitogens were examined, nor were there striking differences in pathology between the treatment groups. The data suggest an important role for natural killer cells in host defense against MCMV. Also, increased susceptibility to MCMV may provide a useful indicator of deficits in the natural killer cell response.

Animals↗
PubMed1982

Oxygen consumption measured with microcomputer-assisted Warburg manometry.

We have developed and tested an automated system that measures in vitro oxygen consumption by Warburg manometry in as many as 16 units that are under the simultaneous control of a microcomputer which requires attention at the beginning of the study only. The all-glass Submarine Volumometers used are readily adapted to automation using a microcomputer that interacts with an infrared photodetector sensitive to manometric changes in the reaction vessel and a stepper motor that can advance the calibrated micrometer in response to these changes. The microcomputer interacts with the user at the start of the study during data entry and subsequently determines volume changes related to oxygen consumption, calculates respiration rates, and prints or graphs the results without further user interaction. We compared this automated system with manual methods by measuring the oxygen consumption of lung tissue slices and by determining the ability of the system to match known volumes entered manually. We found that the results obtained using the automated system were not significantly different from known manual methods (P less than 0.05).

Animals↗
PubMed1982

Dose response of elastase-induced emphysema in hamsters.

Elastase-induced emphysema in hamsters was studied using pulmonary function tests in an effort to develop techniques for determining the effects of air pollutants on the progression of this disease. Single intratracheal injections of 6, 12, or 24 units of porcine pancreatic elastase produced dose-related changes in pulmonary function after 4 wk when compared with sham-injected control animals. Boyle's law end-expiratory volume and residual volume, measured by gas dilution, increased (p less than 0.05) at 12 and 24 units, respectively, whereas vital capacity, determined plethysmographically, and total lung capacity wee increased (p less than 0.05) at all 3 elastase doses. Respiratory system compliance, calculated by a nonlinear least squares regression fit of the deflation pressure-volume curve, increased (p less than 0.05) at 24 units only. The multiple-breath nitrogen washout slope (N2 slope) and the single-breath diffusing capacity for carbon monoxide (DLCO) decreased (p less than 0.05) at all 3 doses of elastase. Both histologic and physiologic evaluation showed dose-related pulmonary impairment. It appears, therefore, that as little as 6 units of elastase produces mild emphysema in hamsters, which is detectable by pulmonary function testing. Of these tests, the DLCO and N2 slope were the most effective in detecting the degree of impairment.

Animals↗
PubMed1981

Fly ash-induced changes in hamster tracheal epithelium in vivo and in vitro.

The effects of fly ash from a coal-fired power plant on tracheal epithelium of crRGH (SYR) Syrian golden hamsters were studied in organ cultures and after in vivo exposures. The tracheal epithelium of animals receiving 5-9 daily (5 d/wk) 3-h exposures to 2 mg fly ash per cubic meter showed large areas of basal cell hyperplasia and stratification. Surface alterations characteristic of stratified metaplasia were observed. Exposure to 1 mg/m3 produced diffuse basal cell hyperplasia. Hamster tracheal ring cultures exposed in vitro to 50 micrograms/ml fly ash for 1 h/d or to 10 micrograms/ml for 3h/d showed epithelial changes similar to those observed in vivo. Whole suckling hamster tracheas in organ culture exposed to fly ash at concentrations of 10 and 50 micrograms/ml for 1 or 3 h/d exhibited cornifying epidermoid metaplasia after 7 exposures. The most characteristic findings in surface cells were broad metaplastic areas with keratin formation.

Air Pollutants↗
PubMed1981

Response of hamster trachea in organ culture to Mount St. Helens volcano ash.

The effects of Mount St. Helens volcanic ash on rings of hamster tracheal epithelium in organ culture were studied. Volcanic ash samples with mass median aerodynamic diameters (MMAD) of 7.7 micrometers and 1.6 micrometers caused markedly different alterations in the tracheal mucosa. Examination by SEM of the ventral epithelial surface of tissue from untreated control explants after 2 weeks in culture showed equal numbers of ciliated and microvillous cells. Examination by SEM of tracheas exposed to the smaller size particles revealed that ash concentrations as low as 1 microgram/ml increased mucous secretion after one 2-hr exposure. After four or nine 2-hr exposures, cells contained cilia that were short and blunt. Ciliary activity after these exposures showed a significant depression in beating frequency. Tracheal ring cultures exposed to the larger volcanic ash particles exhibited moderate cytomorphological changes after one 2-hr exposure at concentrations of 1, 10 and 100 micrograms/ml. As the number of exposures increased, most of the columnar cell layer was lost, resulting in exposure of the basal cells. After nine exposures at the two highest concentrations of ash (10 and 100 micrograms/ml), only a few ciliated cells were remaining. Statistically significant reductions in ciliary activity paralleled the epithelial damage. The degree of epithelial damage and changes in the cilia beating frequency were related to the dose and the number of exposures to the volcanic ash.

Animals↗
PubMed1980

Extrapulmonary effects of NO2 as reflected by pentobarbital-induced sleeping time in mice.

The influence of nitrogen dioxide (NO2) on pentobarbital (PEN)-induced sleeping time (S.T.) was investigated in mice. Acute exposure to concentractions as low as 470 microgram NO2/m3 (0.25 ppm) caused a significant increase in PEN-induced S.T. No significant effects on PEN-induced S.T. were detected after 1 or 2 days (3 h/day) exposure to 235 microgram NO2/m3 (0.125 ppm). None of the exposure regimens affected the time required for the drug to induce sleep. When the effects of repeated daily exposures (3 h/day) to 9400 microgram NO2/m3 (5 ppm) were compared in male and female mice, the females had a significantly increased PEN-induced S.T. after 1 and 2 days of exposure. However, an increase in PEN-induced S.T. was not observed in males until the 3rd day of exposure. Since the duration of PEN-induced S.T. is primarily determined by hepatic mixed function oxidase activity, it is possible that NO2 may alter some aspects of xenobiotic metabolism.

Animals↗