Organ weights and water contents of rats fed purified diets.
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Biomedical subjects
Publications and source records attributed to J M Peters.
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The effect of a metallothionein (MT) antisense oligodeoxynucleotide (ODN) on mouse preimplantation embryo development was investigated. Preimplantation embryos were cultured for 72 h and examined following exposure to either an MT antisense or sense ODN. Blastocyst formation (cavitation) and embryo cell number were lower in embryos exposed to the MT antisense ODN than in controls or in embryos exposed to the MT sense ODN. In embryos cultured in medium containing free nucleotides, cavitation frequency was not affected, although mean embryo cell number was lower than in controls. Combined, this work shows that an antisense ODN against MT can significantly affect blastocyst formation of preimplantation embryos; some, but not all, of the observed effects on embryo cell number may have been due to nucleotide toxicity.
Pulmonary function tests were conducted on 121 curing and 189 control workers in 1972; 87% of the 1972 cohort was resurveyed one year later. The curing workers were subdivided into high and low exposure groups on the basis of environmental sampling. Cross-sectionally, in the 1972 cohort, the residual forced vital capacity was significantly decreased (P greater than .01) among the the heavily exposed workers (266 ml). Longitudinally, the mean one-year loss of forced expiratory volume in one second (FEV1.0) (173 ml/yr) in the curing workers with more than ten years of exposure was significantly greater (P less than .01) than in the control groups. Pulmonary function tests before and after a day's work were conducted on 29 curing-room workers. The eight heavily exposed curing workers had a significant decrease (P less than .05) in FEV1.0 of 115 ml. Our findings are sufficient to conclude that heavy exposure to curing fume affects pulmonary function. We recommend reduction of exposure and further longitudinal studies, especially in regard to those most heavily exposed.
Respiratory questionnaires and pulmonary function tests were administered to sixty-five men exposed to dust in the processing are from three rubber tire manufacturing plants. Similar tests were done on 189 "control" workers. Compared with the controls, the processing workers had a higher prevalence of chronic productive cough. Overall, the processing group showed a decrease in the ratio of FEV to FVC. The processing workers with more than ten years of exposure showed a significant decrease in the ratio of FEV1.0/FVC, the FEV1.0, the residual FEV1.0, and the flow rates at 50% and 25% of the forced vital capacity. None of the pulmonary function effects could be solely explained on the basis of smoking, age, ethnic, or socioeconomic factors: all were related to the length of exposure. Based on these results we conclude that exposure in the processing area produces pulmonary disease.
Pulmonary function tests, chest x-rays, and respiratory questionnaires were administered to eighty talc workers and 189 non-exposed rubber workers from three rubber tire manufacturing plants. The talc workers, who were exposed to talc at levels below the current threshold limit value (TLV) of 20 mppcf for nonfibrous talc, had a statistically significantly greater prevalence of productive cough and of positive criteria for chronic obstructive lung disease (COLD) than did the control workers. The talc workers with more than 10 years of exposure had significantly decreased residual FEV 1.0. Multiple regression analysis of FEV 1.0 in the talc workers estimated that each year of exposure to talc dust reduced the FEV 1.0 by 26 ml. Talc workers had a clear increase in respiratory morbidity, despite the absence of chest roentgenographic changes. Based on this study, a safe exposure level for talc appears to be 25 mg/m3 as a time-weighted average.
The peroxisome proliferator-activated receptor alpha (PPAR alpha) is the mediator of the biological effects of peroxisome proliferators through control of gene transcription. To determine if the toxic effects of di(2-ethylhexyl)phthalate (DEHP) are mediated by PPAR alpha, we examined its effect in PPAR alpha-null mice. Male Sv/129 mice, PPAR alpha-null (-/-) or wild-type (+/+) were fed ad libitum either a control diet or one containing 12,000 ppm DEHP for up to 24 wk. Significant body weight loss and high mortality was observed in (+/+) mice fed DEHP. By 16 wk, all DEHP-fed (+/+) mice had died of cystic renal tubular disease. In contrast, the (-/-) mice fed DEHP had no changes in body weight until later in the study nor increased mortality. Histologically, (+/+) mice fed DEHP had typical toxic lesions in liver, kidney, and testis while (-/-) mice fed DEHP had no toxic liver lesions but did show evidence of toxicity in kidney and testis after 4-8 wk of feeding, which progressed into moderate lesions by 24 wk. Analysis of hepatic and renal mRNAs showed a typical pleiotropic response in gene expression in the DEHP-fed (+/+) mice that was absent in the DEHP-fed (-/-) mice. These results provide evidence that PPAR alpha mediates the subacute-chronic toxicity of DEHP in liver, kidney, and testis. However, because (-/-) mice did develop toxic lesions in kidney and testis, DEHP can also act through PPAR alpha-independent pathways in mediating renal and testicular toxicity.
One hundred twenty-one men who were exposed to tire-curing fumes responded to respiratory symptom questionnaires. Results were compared with questionnaires of 189 nonexposed workers who were employed by the same three tire manufacturing plants. The curing workers had a higher prevalence of chronic bronchitis than the controls. Of the curing workers with more than ten years of experience to fumes, 25% met the criteria for the epidemiological diagnosis of chronic obstructive pulmonary disease. Increased respiratory morbidity in the curing workers was related to both intensity and length of exposure to fumes. Because cigarette smoking and other variables cannot explain the difference between the curing and control groups, we attribute the greater prevalence of respiratory morbidity to exposure to curing fumes. These findings warrant further longitudinal studies and reduction of exposure, especially for workers on the manual automobile tire presses, which is the high-exposure group.
In order to evaluate regional muscle blood flow and oxygen utilization, we study with positron emission tomography (PET) the distribution of C15O2 and 15O2 in 17 subjects: 5 normals (24 +/- 3 years) and 12 patients (63 +/- 13.5 years). C15O2 and 15O2 are inhalated with a steady-state technique. Positron tomograms are recorded in supine position at the greatest diameter of the leg. Exercise consists in simultaneous ankle flexions. In all normals, C15O2 and 15O2 are distributed homogeneously and symmetrically in both legs. At rest, they concentrate in the region of vascular pedicle. After exercise, C15O2 and 15O2 are electively distributed in the anterolateral region of the leg. In patients, this pattern of distribution is similar but asymmetrical. Moreover, the regional uptake of C15O2 and 15O2 often dissociates. In conclusion, C15O2 and 15O2 allow to study repeatedly muscle blood flow and oxygen utilization in patients with peripheral ischemia, both at rest and after exercise. The broad spectrum of pathological changes observed in this study needs further metabolic investigations.