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Biomedical subjects

M W Carter

Publications and source records attributed to M W Carter.

At least 37 records · Page 2Linked to original sources

Developmental toxicity of nine selected compounds following prenatal exposure in the mouse: naphthalene, p-nitrophenol, sodium selenite, dimethyl phthalate, ethylenethiourea, and four glycol ether derivatives.

Ethylene glycol dimethyl ether (EGdiME), diethylene glycol dimethyl ether (diEGdiME), triethylene glycol dimethyl ether (triEGdiME), diethylene glycol diethyl ether (diEGdiEE), ethylenethiourea (ETU), sodium selenite (SS), dimethyl phthalate (DMP), naphthalene (NAP), or p-nitrophenol (PNP) were administered by gavage for eight consecutive days to female CD-1 mice. Weight loss was insensitive as an index of sublethal adult toxicity and was inadequate for determining a maximum tolerated dose. LD50 values indicate that SS, NAP, and PNP were more toxic (8.4, 353.6, and 625.7 mg/kg, respectively) than the polyglycol ethers, ETU, and DMP (LD50 values ranged from 2525.8 to 6281.9 mg/kg). Each of the compounds was administered on d 7 through 14 to pregnant animals at a single dose estimated to be at or just below the threshold of adult lethality. In such a reproductive study, each of the compounds could be categorized on the basis of the pattern of maternal lethality and fetotoxicity which it produced. The number of dams with complete resorptions was significantly increased after administration of ETU, and no mice in the EGdiME-, diEGdiME-, or triEGdiME-treated groups delivered any viable offspring. Maternal lethality was significant in the EGdiME, triEGdiME, PNP, and NAP groups. There was a slight reduction in the average number of live pups per litter in the diEGdiEE- and PNP-treated groups and a significant reduction in the NAP group. The number dead per litter was increased with diEGdiEE. SS and DMP had no effect on maternal or fetal survival at the doses administered. Individual pup weight at d 1 postpartum was only significantly reduced by diEGdiEE, and no gross congenital abnormalities were detected in neonates from any treatment group. These results provide guidelines for the subsequent toxicity testing of these chemicals.

Administration, Oral↗

Compliance and policy issues and recommendations related to revision of the National Interim Primary Drinking Water Regulations for Radionuclides.

This paper summarizes the deliberations and conclusions of the Compliance and Policy Committee of the National Workshop for Radioactivity in Drinking Water. Prior to and during the workshop the committee considered a total of 32 possible compliance and policy issues and determined that 22 were valid. The committee developed positions on seven of these and these positions are presented herein. The remaining 25 issues are also listed with the committee's evaluation of each.

Legislation as Topic↗

Wheat-sensitive enteropathy in Irish setter dogs: possible age-related brush border abnormalities.

The pathogenesis of a wheat-sensitive enteropathy was explored in a litter bred from two Irish setters with a naturally occurring enteropathy. Jejunal biopsies from all eight progeny exhibited morphological changes comparable to those in the parents, while biochemical abnormalities appeared to be related to age. In biopsies obtained from the first group of four dogs at eight months, the activities of alkaline phosphatase and of leucyl-2-naphthylamidase were almost undetectable while disaccharidases were unaltered. In contrast, analytical subcellular fractionation of biopsies obtained from the second group of four dogs at nine months showed that specific activities now reflected a major deficiency of brush border alkaline phosphatase, and normal brush border leucyl-2-naphthylamidase accompanied by elevated soluble activity. Further studies are indicated to determine whether these findings represent an age-related abnormality affecting specific microvillus membrane proteins.

Age Factors↗

The relationship between prenatal lethality or fetal weight and intrauterine position in rats exposed to diethylstilbestrol, zeranol, 3,4,3',4'-tetrachlorobiphenyl, or cadmium.

When administered orally during gestation, diethylstilbestrol (DES), zeranol (ZN), and 3,4,3',4'-tetrachlorobiphenyl (4CB) but not cadmium (Cd) exhibited significant developmental toxicity, including elevated embryo- and fetolethality and reduced fetal weight, in Sprague-Dawley rats. An analysis was performed to determine the effect of intrauterine position on these parameters. In control dams sacrificed after day 18, the general pattern was that fetuses at the ovarian end of the uterine horns were significantly lighter in weight, while the heavier fetuses were located in middle positions. Treatment with each of the chemicals reduced fetal weight equally across all uterine positions. An inverse of the weight pattern was observed for prenatal mortality in controls. Embryonic resorptions were relatively more frequent at both ovarian and cervical ends, while conceptuses at intermediate positions were less vulnerable. No significant alterations in this pattern were observed in treated litters. The frequency of late fetal deaths in 4CB-treated litters was significantly higher at the cervical end of the horn, however. No differences between horns or between sexes were observed in the relative position patterns for either weight or mortality.

Animals↗

Biochemical changes in the jejunal mucosa of dogs with a naturally occurring enteropathy associated with bacterial overgrowth.

The subcellular biochemical features of a naturally occurring enteropathy in the dog associated with bacterial overgrowth have been examined. Affected animals comprised a group of 10 German Shepherd dogs with raised serum folate and reduced vitamin B12 concentrations, mild steatorrhoea, reduced xylose absorption, and normal exocrine pancreatic function. Culture of duodenal juice showed bacterial overgrowth with mixed flora, most frequently including enterococci and Escherichia coli. Examination of peroral jejunal biopsies revealed predominantly minimal histological but distinct biochemical abnormalities in the mucosa. The specific activity of alkaline phosphatase was decreased, isopycnic density gradient centrifugation showing a marked loss particularly of the brush border component of enzyme activity. In contrast, gamma-glutamyl transferase activity was enhanced in brush border fragments of slightly increased modal density, but there were no changes in the activities of the carbohydrases, zinc-resistant alpha-glucosidase, maltase, sucrase, and lactase or of the peptidase, leucyl-2-naphthylamidase. Activities of lysosomal enzymes were increased and there was evidence for enhanced lysosomal fragility and mitochondrial disruption. The activities and density gradient distributions of marker enzymes for basal-lateral membranes, endoplasmic reticulum and peroxisomes were essentially unaltered. These findings show that bacterial colonisation of the proximal small intestine may be associated with specific alterations in microvillus membrane proteins and provide biochemical evidence for intracellular damage to the enterocytes.

Animals↗

Morphological and biochemical studies of a naturally occurring enteropathy in the Irish setter dog: a comparison with coeliac disease in man.

A naturally occurring enteropathy was identified in Irish setter dogs and wheat-sensitivity was demonstrated in a litter bred from two of the affected animals. The morphological and biochemical features of this enteropathy are described and compared to coeliac disease in man. Affected animals comprised 10 dogs that presented with poor weight gain or weight loss, with or without diarrhoea. Exocrine pancreatic function was normal and culture of duodenal juice demonstrated no marked bacterial overgrowth. Serum vitamin B12 concentrations were unaltered, but in some cases low serum and erythrocyte folate concentrations and reduced xylose absorption provided indirect evidence for proximal small intestinal disease. Examination of peroral jejunal biopsies revealed patchy morphological changes within individual animals, comprising predominantly partial, but in one case subtotal, villous atrophy. Brush border enzymes were selectively altered: the specific activities of alkaline phosphatase, leucyl-2-naphthylamidase and of zinc-resistant alpha-glucosidase were reduced by approximately 40 per cent, while activities of maltase, sucrase, lactase and gamma-glutamyl transferase were unaltered. Activity of a lysosomal enzyme was increased and there was evidence for enhanced lysosomal fragility. The activity of malate dehydrogenase, with a dual mitochondrial and cytoplasmic localisation, was decreased but there were no changes in the activities of marker enzymes for basal-lateral membranes, endoplasmic reticulum or peroxisomes. These findings, particularly the specific biochemical abnormalities, were comparable to those in partially treated coeliac disease in man; however, a specific role for wheat in the pathogenesis of the disease has yet to be defined.

Animals↗

Bacterial overgrowth associated with a naturally occurring enteropathy in the German shepherd dog.

Quantitative and qualitative bacteriological studies were performed on duodenal juice from 19 dogs with chronic small intestinal disease. Bacterial overgrowth was demonstrated in seven German shepherd dogs with minimal histological but specific biochemical abnormalities in the jejunal mucosa. Most frequently this overgrowth comprised bacteria of the normal flora, particularly Escherichia coli and enterococci, but these were occasionally accompanied by bacteria rarely present in the proximal small intestine of the normal dog, particularly Clostridium species. In most cases this overgrowth was associated with raised serum folate and reduced serum vitamin B12 concentrations, a finding consistent with the capacity of many enteric bacteria to synthesise folate and bind vitamin B12.

Animals↗

Indicators of developmental toxicity following prenatal administration of hormonally active compounds in the rat. I. Gestational length.

Prenatal administration of 3,4,3',4'-tetrachlorobiphenyl, zeranol, or diethylstilbestrol was observed to delay parturition in the rat and result in a concomitant increase in perinatal mortality. Even among control animals, those litters in which birth occurred after the beginning of day 22 of pregnancy contained significantly fewer survivors one day after birth. Increases in the length of gestation were correlated with increased weight of newborn control pups independent of litter size. The relationship between weight and litter size was anomalous, however, in treated animals. Gestational length is a sensitive indicator of a developmental effect even in the absence of overt teratogenicity.

Animals↗

Transportation of radioactive material in Georgia.

A 3-yr study of radioactive materials transportation examined the magnitude of radioactive materials shipments in terms of numbers of packages and motor vehicle trips and types of materials; compliance with regulations for packaging, labelling, handling, external radiation exposure, and surface contamination; and dose to workers as measured with personnel dosimeters. Much of the information was obtained at the Atlanta airport and its vicinity, a package distribution center for the southeastern U.S., and at the Barnwell, S.C. radioactive waste burial site, the destination of most shipments of radioactive waste from or through Georgia. Approximately 12,000 packages in radioactive material categories I, II and III were handled in Georgia each year. Motor vehicles made approximately 3300 trips per year. Some instances of noncompliance were observed, but few of them had the potential for elevated radiation exposure of persons. Several incidents associated with radioactive material transport are reported, of which one may have resulted in slightly elevated exposures to persons. Among drivers and handlers who worked with radioactive material shipments, dosimeters showed that less than one-half of them received radiation doses above background levels. The highest doses were found for drivers who transported large numbers of 99Mo generators.

Georgia↗

Covariance analyses with heterogeneity of slopes in fixed models.

Techniques that describe the use of covariance when heterogeneity of slopes exists are severely limited. Although a few procedures for model selection have been recommended, none, except the hierarchical approach, is straightforward and usable with present computer programs. The hierarchical subset selection procedure presented in this paper is based on the proposition that heterogeneity may be present only for certain terms in the model. After hierarchical selection, those terms which do not involve heterogeneity are interpreted as in the usual analysis for covariance. The interpretations of those terms which do involve heterogeneity are modified with respect to significance tests performed at various values of the covariate. The hierarchical subset selection method allows one to investigate heterogeneity of slopes in covariance models as functions of the classification variables present in the design.

Analysis of Variance↗

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↗