The hepatic steatosis observed in the influenza B virus mouse model of Reye syndrome has been attributed to infectious virus or, alternately, to decreased food intake in the virus-treated mice or impurities in the virus preparation. To resolve this issue, 4- to 6-wk-old male Balb C mice were given, by intravenous injection, 12,800 hemagglutination units of influenza B Lee/40 virus in phosphate buffered saline/1% bovine serum albumin using virus prepared by ultra-centrifugation from infected allantoic fluid, by sucrose density-gradient purification of virus prepared by ultracentrifugation from infected allantoic fluid or by irradiation of virus prepared by ultracentrifugation from infected allantoic fluid to inactivate virus. The infectivity titer of virus prepared by ultracentrifugation from infected allantoic fluid was much higher than that of sucrose density-gradient purified virus prepared from infected allantoic fluid: 50% egg infectious dose for virus prepared by ultracentrifugation from infected allantoic fluid was 3.9 x 10(4)/hemagglutination unit vs. 8.7 50% egg infectious dose/hemagglutination unit for sucrose density-gradient purified virus prepared from infected allantoic fluid. Control mice received phosphate-buffered saline/1% bovine serum albumin or uninfected allantoic fluid diluted in phosphate-buffered saline/1% bovine serum albumin. Mice were fasted to eliminate dietary variation, and livers were obtained 36 hr after virus administration. Of the above treatments, only virus prepared by ultracentrifugation from infected allantoic fluid caused clinical illness and increased hepatic triglycerides (p less than 0.02) compared with controls. Hepatic triglycerides in virus prepared by ultracentrifugation from infected allantoic fluid correlated with histopathological vacuolization scores (r = 0.5773; p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
An oncofetal protein (OFP), which is a potential marker for carcinogenesis and tumorigenesis, was evaluated with monoclonal antibodies shown to be specific for the antigen. Treatment of partially hepatectomized rats with a single non-necrogenic dose of diethylnitrosamine induced OFP in the liver. Its concentration, as measured by a dual immuno/bioassay, increased steadily over a 5-week period of observation before reaching a constant level. Immunohistochemical localization of OFP in liver sections from rats treated with N-nitroso-N-diethyl-nitrosamine showed that the factor was primarily localized to the cell cytoplasm in cells of most of the altered hepatic foci although some of this shedding antigen was also extracellular. Monoclonal antibody 17-1A specific for 17-1A antigen, an established surface marker for adenocarcinomas of the gastrointestinal tract, showed a similar distribution in liver from the carcinogen-treated rats, but localized to the cell membrane and cytoplasm. Scattered cells surrounding the altered hepatic foci were also positive for both monoclonal antibodies. Immunolocalization studies showed fetal rat liver and hepatoma were positive for OFP but adult normal or regenerating liver was negative. It was not detected in cells which morphologically could be classified as oval cells. As assessed by immuno/bioassay, the OFP released to the peripheral blood (plasma) of hepato-carcinogen-treated rats increased for 3 weeks, before undergoing a transitory decrease. Circulating antibodies specific for the factor were detected in the blood around 3-5 weeks post-treatment. Development of Western blots of the OFP with antiphosphotyrosine IgG indicates that the marker protein contains phosphotyrosine.
ABSTRACT. Previous studies have demonstrated alterations in plasma free fatty acid content in Reye's syndrome (RS). We have therefore studied erythrocyte membrane lipids to determine if there are concomitant structural and functional modifications attributable to RS. Erythrocyte lipids were measured in children with RS and in critically ill children also requiring intensive care (ICU). In comatose RS patients erythrocyte phospholipid arachidonate was increased 2-fold relative to control ICU patients: 20.46 f 2.14 versus 10.41 f 2.32% of total erythrocyte phospholipid, p < 0.05. RS coma patients also demonstrated an increased ratio of erythrocyte phospholipid polyunsaturatedlsaturated fatty acids (0.76 f 0.10) compared to ICU controls (0.48 f 0.08, p < 0.05). Erythrocyte cholesterol was higher in RS patients (79.00 f 6.61 pg/mg protein) than in ICU controls (59.74 f 6.09, p < 0.05). Erythrocyte malondialdehyde generation was decreased in comatose RS patients (404 rl: 28 nmol malondialdehyde/g hemoglobin) versus ICU (517 f 29, p < 0.05). Although plasma vitamin E was depressed in RS patients, the erythrocyte vitamin E concentrations were no different in RS patients than in ICU patients. All RS patients had a typical viral prodrome and either a history of aspirin intake and/or measurable serum salicylate on admission. All of the biochemical abnormalities in RS patients listed above returned to values comparable to those of healthy RS siblings on recovery. The transient nature of these phenomena suggests that they were related to viral infection and/or aspirin rather than to intrinsic differences in lipid metabolism between RS patients and controls. (Pediatr Res 21: 352-356,1987)
Calcium glucarate and N-(4-hydroxyphenyl)-retinamide were evaluated individually and in combination in the diet as preventative chemical agents, by using the induction of rat mammary tumors by 7,12-dimethylbenz[alanthracene as the test system. When tested separately over 18 weeks, optimal doses of calcium glucarate (128 mmol/kg of diet) or N-(4-hydroxyphenyl)retinamide (1.5 mmol/kg of diet) administered daily inhibited tumor incidence by 50% or 57% and tumor multiplicity by 50% or 65%, respectively. Suboptimal doses of calcium glucarate (32 mmol/kg) and of N-(4-hydroxyphenyl)-retinamide (0.75 mmol/kg) inhibited tumor incidence by 15% and 5% but had no inhibitory effect on tumor multiplicity. In contrast, the combination of calcium glucarate (32 mmol/kg) and N-(4-hydroxyphenyl)retinamide (0.75 mmol/kg) inhibited tumor incidence and tumor multiplicity by 50%. Similar synergism was observed with the combination of calcium glucarate (64 mmol/kg) and N-(4-hydroxyphenyl)retinamide (0.75 mmol/kg), the inhibition being 55460%. HPLC Retinoids have also been shown to inhibit the neoplastic transformation of mammary tissue by carcinogenic hydrocarbons in whole-organ culture (7). The inhibition of carcinogen-induced tumors by HPR has been confirmed and the mechanisms underlying this inhibition have been investigated (8). The effect of limiting feeding of retinoids to specific time periods of the carcinogenic process has also been reported (7,9). Although retinyl acetate tends to accumulate in the liver resulting in mild hepatotoxicity, HPR does not have this disadvantage (5). A comprehensive study has been made of HPR metabolism in the rat (10). The overwhelming evidence suggests that retinoids are inhibitory to the initiation and promotion phases of rat mammary carcinogenesis (11).Studies from this laboratory have shown that dietary calcium glucarate (CGT) is an effective preventative chemical (chemopreventative) agent against cancer induction in several rodent organs, including the mammary gland (12, 13). This activity is believed to derive from the slow conversion of approximately one-third of the CGT to the potent f3-glucuronidase inhibitor D-glucaro-1,4-lactone, at the acid pH of the stomach. The increased net glucuronidation could theoretically lead to increased excretion of carcinogens and promoting agents, including steroid hormones, as glucuronide conjugates (12)(13)(14). Consequently, CGT has been observed to inhibit the initiation and promotion phases of tumorigenesis.The The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. §1734 solely to indicate this fact.
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