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Biomedical subjects

M W Carter

Publications and source records attributed to M W Carter.

14 recordsLinked to original sources

Fetotoxic alterations in the normal ontogenies of rat microsomal and lysosomal enzymes.

The activity patterns during development for acid phosphatase (Ac-P), alkaline phosphatase (A1-P), beta-glucuronidase (beta G), and UDP-glucuronyltransferase (UDPGT) have been determined in various tissues of the rat for corn oil and distilled water controls as well as in animals prenatally exposed to four fetotoxic chemicals. Postnatal assays were performed on both sexes separately. In control animals, tissue-specific differences between male and female activity levels were found for UDPGT. In the liver of mature offspring, enzyme activity was greater in males than in females. Although no sex difference was observed in the intestine, the kidneys of females exhibited higher values than those of males. An original computer-assisted methodology is presented, designed (a) to permit a mathematical description for the complex curves exhibited by these ontogeny profiles, and (b) to assess the statistical significance of chemical-induced alterations in these complex developmental patterns, specifically, to target sensitive periods and subtle changes near the fetotoxic threshold. Oral administration (days 6-18 of gestation) of 3,3',4,4'-tetrachlorobiphenyl (4CB) to pregnant females resulted in an induction of liver UDPGT activity in offspring postnatally, and some alterations in the perinatal pattern of beta G in the same tissue. This treatment also produced differences in the intestinal patterns of Ac-P and male UDPGT. No significant changes were observed in offspring exposed to diethylstilbestrol (DES). Treatment with zeranol (ZN) caused reductions in activity over the entire postnatal period for beta G in liver, brain, intestine, and kidney, for A1-P in brain, and for Ac-P in the intestine. Cadmium-treated dams gave birth to offspring that exhibited slightly altered ontogenies only in intestine for UDPGT and AcP. The alterations in these developmental profiles indicate periods of increased sensitivity, and may be useful in directing more specific studies into the fetotoxic mechanisms of these compounds.

Acid Phosphatase

Diethylstilbestrol-induced perinatal lethality in the rat. I. Relationship to reduced maternal weight gain.

An analysis was performed to determine the mechanism of depressed maternal weight gain and its effect on perinatal lethality following prenatal exposure to diethylstilbestrol (DES). Pregnant Sprague-Dawley rats were dosed orally by gavage with DES or corn oil (control) during various intervals of gestation. The maternal weight-gain patterns of control and treated dams and the number of live offspring were recorded. The amounts of feed and water intake and feces and urine output in pregnant dams were measured, and metabolic rate and thyroid hormone levels were also determined. DES (at 45 micrograms/kg/day) was embryo- and fetolethal during implantation and parturition, and there was an accompanying decline in maternal weight. Growth of adult males, nonpregnant females, and weanlings of both sexes was also depressed. During pregnancy, the net intake of feed and water was not altered by the drug, but maternal serum thyroxine and metabolic rate were significantly elevated. Reduced metabolic efficiency, then, is the likely mechanism for weight depression. Reduction of maternal weight gain during pregnancy by DES is a diagnostic indicator of fetolethality, but is probably not causally related to it.

Animals

Nucleotide sequence and taxonomic value of the major outer membrane protein gene of Chlamydia pneumoniae IOL-207.

Chlamydia pneumoniae IOL-207 genomic DNA was hybridized with a 1.5 kb labelled DNA probe containing the 3' region of the coding sequence for the major outer membrane protein (MOMP) of C. trachomatis serovar L1. An 8.5 kb Bg/II fragment containing the complete MOMP gene was cloned into lambda EMBL3. Two hybridizing EcoRI fragments were sub-cloned into the lambda ZAP II cloning vector and the resulting plasmids were used as templates for sequencing both strands of the C. pneumoniae MOMP gene. Computer taxonomic studies using the nucleotide and inferred amino acid sequence of the MOMP of C. pneumoniae IOL-207 and all known chlamydial MOMP sequences supported the designation of C. pneumoniae as a new species, but electron microscope studies suggested that the presence of pear-shaped elementary bodies (EBs) may not be a reliable taxonomic criterion.

Amino Acid Sequence

Induction of maternal toxicity in the rat by dermal application of retinoic acid and its effect on fetal outcome.

Time-mated Sprague-Dawley rats were administered all-trans-retinoic acid (RA) dermally on gestational days 11 through 14 at three dosage levels (25, 100, and 250 mg/kg body weight). Dams administered ethylenethiourea (ETU) dermally on gestational days 11 to 12 or RA orally on day 12 were used to indicate the strain's sensitivity to teratogenesis. The chemicals were dissolved in dimethylsulfoxide (DMSO) for dermal application or suspended in corn oil for treatment by gavage. The maternal weight gain, pup weight, number of resorptions and number of fetuses with gross malformations, and skeletal/organ-level anomalies were determined. Beginning with day 15, dams dermally treated with RA exhibited dermal lesions at the site of application, most dams showed vaginal bleeding by day 16, and approximately 20% did not survive to day 19. Relative to the DMSO control group, maternal weight gain in the dermal RA groups was decreased by approximately 50% at the lowest dose, with essentially no weight gain at the intermediate- and high-dose levels. The decrease in average fetal weight at the two higher doses was significant, whereas the resorption and malformation frequencies were not significantly increased by dermal treatment with RA. Without significantly affecting fetal weight or resorption frequency, dermal application of ETU significantly increased the frequency of skeletal anomalies, primarily tail defects. Oral administration of RA did not increase the malformation frequency nor produce significant maternal or fetotoxic effects. In summary, treatment of pregnant Sprague-Dawley rats by dermal application of RA dissolved in DMSO resulted in significant toxicity to the dam.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced

Technique for estimating fetal mouse thoracic volumes through image analysis of histological sections.

In a previous study we estimated fetal mouse thoracic volume by use of paraffin casts. While this procedure provided useful information, it did not allow histologic examination of thoracic viscera. In the present study the thoracic volumes of day 14-18 fetal mice were determined through serial histological sections. The thoracic cavity was traced from the sections and the area of each tracing was determined by computer image analysis. These areas were summed and then multiplied by the thickness of each section to derive the thoracic volume. This procedure thus permitted both volumetric determinations and histological inspection of the thoracic viscera. In addition, two randomized sampling methods designed to increase the utility of such volumetric estimates were compared for reliability. The method best suited for this study was a random stratified sampling method because it reproduced estimates with minimal standard deviation.

Animals

A retrospective epidemiological study of morbidity at a large western copper smelter.

Smelter workers were compared with employees at the mine, concentrator and refinery in an attempt to discover if the smelter environment has an effect on morbidity. The data for the study consisted of weekly indemnity insurance claim forms. It was found that the refinery, rather than the smelter, had the highest percent of employees submitting claims. Other major comparisons of morbidity among the four plants also showed the refinery to be highest, with the smelter closer to the mine and concentrator. This pattern was found to hold for respiratory disease classifications as well as overall morbidity levels.

Humans

A retrospective epidemiological study of mortality at a large western copper smelter.

In comparing the smelter with the mine, concentrator, and State of Utah, it was found that they were very similar in the percentage of deaths due to all causes except lung cancer; 7.0% of all deaths at the smelter were due to lung cancer compared to 2.2% for the mine, 2.2% for the concentrator, and 2.7% for the state. The excess at the smelter was statistically significant. Approximate age-adjusted death rates were obtained for various causes of death. The rates for the smelter are higher than for the mine and the state for lung cancer and for all causes combined. The average age at death for smelter workers is nearly the same as for mine employees, even for those who died of lung cancer. Smoking data was examined and there was no indication of a smoking synergism. Cumulative exposure indices for SO2, H2SO4 mist, As, Pb, and Cu were computed for each deceased smelter worker based n the length of time he worked in each of 12 major areas. Those who died of lung cancer had the highest average exposure index for all five constituents. Stack emission data showed much higher levels of As and SO2 prior to 1959.

Adult