Biomedical subjects
K M Nauss
Publications and source records attributed to K M Nauss.
The toxicity of inhaled methanol vapors.
Methanol could become a major automotive fuel in the U.S., and its use may result in increased exposure of the public to methanol vapor. Nearly all of the available information on methanol toxicity in humans relates to the consequences of acute, rather than chronic, exposures. Acute methanol toxicity evolves in a well-understood pattern and consists of an uncompensated metabolic acidosis with superimposed toxicity to the visual system. The toxic properties of methanol are rooted in the factors that govern both the conversion of methanol to formic acid and the subsequent metabolism of formate to carbon dioxide in the folate pathway. In short, the toxic syndrome sets in if formate generation continues at a rate that exceeds its rate of metabolism. Current evidence indicates that formate accumulation will not challenge the metabolic capacity of the folate pathway at the anticipated levels of exposure to automotive methanol vapor.
Natural killer cell activity and autologous mixed lymphocyte response of splenic, mesenteric lymph node, and colonic lymphocytes during DMH-induced colon carcinogenesis in the rat.
Two in vitro models of immune surveillance were used to examine the immune status of the gut-associated lymphoid tissue, mesenteric lymph nodes, and spleen during the early stages of 1,2-dimethylhydrazine (DMN)-induced colon tumorigenesis. DMH- and vehicle-treated Fischer rats were sacrificed at one of three time points: one week, two months, or five months after cessation of treatment. Colonic, lymph node, and splenic natural killer cell cytolytic activity toward YAC-1 tumor targets and T-cell response to autologous Ia-induced blastogenesis were measured at each time point. We found little change in natural killer cell activity or T-cell proliferation induced by autologous Ia gene products at these time periods.
Dietary fat and fiber: relationship to caloric intake, body growth, and colon tumorigenesis.
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Effect of beef fat on DMH-induced colon tumorigenesis: influence of rat strain and nutrient composition.
The modulating effect of high levels of dietary fat on chemically induced colon tumorigenesis has been studied in animal models, with conflicting results. The present study was designed to examine the influence of rat strain, stage of tumor development and micronutrient composition of the diet on 1,2-dimethylhydrazine (DMH)-induced intestinal tumorigenesis. Two strains of rats [Sprague-Dawley (SD) and Fischer-344 (F-344)] were fed one of three experimental diets. The diets contained 5 or 20% dietary fat but differed in nutrient composition and nutrient-energy ratio. After receiving the experimental diets for 4 wk, animals were treated with DMH X 2HCl (10 mg/kg body wt) once a week for 20 wk and killed 10 wk after receiving the last dose of carcinogen. Long-term administration of DMH was more toxic to F-344 rats than to SD animals, and the toxicity was potentiated by reductions in the micronutrient composition of the diet. High levels of dietary fat (20%) resulted in a barely significantly higher incidence in colon tumor (but not frequency or size) in SD rats that received the diet promoting optimal growth than did low levels of dietary fat. No effect of 20% beef fat was seen in SD animals fed a diet that produced a slower growth rate or in F-344 animals.
Effect of vitamin A nutriture on experimental esophageal carcinogenesis.
The effect of mild vitamin A deficiency or vitamin A supplementation on methylbenzylnitrosamine (MBN; CAS: 937-40-6)-induced esophageal carcinogenesis was examined in Sprague-Dawley rats. The animals were fed semipurified diets containing levels of retinyl acetate, which were adequate (2.2 mg/kg diet), deficient (0.30 mg/kg diet), or supplemented (29.9 mg/kg diet) with respect to vitamin A content. Carcinogen-treated rats received 2.5 mg MBN/kg (body wt) twice a week for 5 weeks; they were then sacrificed for evaluation of esophageal tumorigenesis 15 weeks later. Liver levels of retinol reflected vitamin A nutriture, but there were no clinical signs of deficiency or toxicity. There were no significant differences in the frequency or incidence of esophageal tumors (either carcinomas or papillomas) among the dietary groups. There was also no indication that either vitamin A deficiency or vitamin A supplementation influenced the formation of preneoplastic lesions. Although the time was short for the neoplastic development, tumors were observed. These data suggest that vitamin A is selective in tissues it may protect from cancer induction and that the esophagus is less involved than other tissues.
Dietary fat and colon cancer: variable results in animal models.
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Rodent models for carcinoma of the colon.
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Ocular infection with herpes simplex virus (HSV-1) in vitamin A-deficient and control rats.
An experimental model was developed for studying ocular infections with herpes simplex virus (HSV) type 1 in vitamin A-deficient (-A) and pair-fed control (+A) rats. The severity and course of the disease was evaluated by clinical examination, slit lamp biomicroscopy and histopathologic observations. Experimental animals were in good health and were infected in the early stages of vitamin deficiency (either prior to or at the beginning of the weight plateau). In all trials the onset of herpetic keratitis was more rapid and the clinical disease more severe in -A rats compared to +A controls. Mean slit lamp scores (which assessed the severity of the corneal disease) increased from 3 to 10 d after infection and were higher (P less than 0.002) in -A rats at all time points and doses of virus tested. The inflammatory response in the cornea and uveal tract of -A rats was significantly higher than that of +A animals. Since ocular HSV disease is a common cause of blindness, the availability of a rat model should be valuable in studies of the role of nutritional factors in host susceptibility and response to viral challenge. Mild vitamin A deficiency increased the severity of experimental corneal HSV infections and resulted in a high incidence of epithelial ulceration and necrosis.
The effect of vitamin A deficiency on the in vitro cellular immune response of rats.
The effect of vitamin A deficiency on the response of splenic lymphocytes to mitogenic stimulation was determined in an experimental rat model. Male Lewis rats were divided into three groups. The ad libitum group (AL) was fed unlimited amounts of a vitamin A-supplemented diet. The vitamin A-deficient group (DEF) received a commercial vitamin A-free diet. The pair-fed group (PF) received a vitamin A-containing diet equivalent in amount to that consumed by the DEP group. During the early stages of vitamin A deficiency (determined by cessation of weight gain), the rats were killed and the isolated splenic lymphocytes subjected to mitogenic stimulation. Lymphocytes from DEF rats had one-third the transformation response to the mitogens Concanavalin A, Phytohemagglutinin and E. coli Lipopolysaccharide S of the AL and PF groups. When the DEF rats were supplemented with vitamin A, the transformation response returned to control values within 3 days. In addition to the alterations in the immune response, the DEF rats showed a marked leukopenia, a decrease in the number of circulating lymphocytes and an increase in the number of circulating neutrophils.