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Biomedical subjects

J H Gans

Publications and source records attributed to J H Gans.

At least 19 recordsLinked to original sources

Liver scarring induced by polychlorinated biphenyl administration to mice previously treated with diethylnitrosamine.

Exposure of mice for 8 weeks to drinking water containing diethylnitrosamine (DEN) was accompanied by alterations in hepatocyte structure and varying degrees of liver nonparenchymal cell (NPC) proliferation. Eighteen and a half weeks after cessation of DEN exposure, there was a 47% incidence of hepatocellular nodules. Centrilobular hepatocyte hypertrophy occurred consistently in mice given intraperitoneal injections of the polychlorinated biphenyl (PCB) mixture Aroclor 1254. PCB administration to mice previously treated with DEN was not accompanied by increases in gross liver nodule incidence above that induced by DEN, but many more developing microscopic nodules within the liver were observed in DEN-treated mice given Aroclor 1254 than in mice treated only with DEN. Aroclor 1254 administration over a 16-week period to mice previously treated with DEN was accompanied by an 83% incidence of severe distortion of liver structure resulting from nodule formation, uneven patterns of hepatocyte growth, and extensive deposition of scar tissue containing proliferating bile ducts. Morphological evidence of intestinal metaplasia was observed in proliferating bile duct-like structures during an early stage of liver adenofibrosis.

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Comparative toxicities of dietary caffeine and theobromine in the rat.

Caffeine, incorporated into pulverized Purina Rat Chow at a concentration of 0.5%, was fed to male Sprague-Dawley rats for 7 or 8 wk and the effects were compared with those of 0.8% dietary theobromine, fed to male rats for 7 wk. Both dietary methylated xanthines produced significant decreases in food consumption and body-weight gain when compared to their respective control groups. Food consumption of caffeine-fed rats was 57.2% of controls and for theobromine-fed rats it was 77.9% of the respective controls. Theobromine produced significant decreases in thymus weights, with caffeine producing smaller decreases. The theobromine-fed rats showed severe testicular atrophy with extensive spermatogenic cell degeneration and necrosis, while the testes of rats fed caffeine for 7 or 8 wk showed only scattered vacuolar degeneration of spermatogenic cells. Caffeine appears to be more potent than theobromine as an anorexic agent in rats, but to be equivalent to theobromine in its potential for inducing thymic atrophy and spermatogenic cell destruction with testicular atrophy.

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Liver nuclear DNA synthesis in mice following carbon tetrachloride administration or partial hepatectomy.

Long-term, continuous (twice per week) administration of CCl4 to male mice resulted in a high incidence of liver nodules which appeared to be resistant to the necrotizing effects of CCl4 but showed no features of malignant neoplasia. Liver nuclear DNA synthesis was compared in mice given CCl4 and in mice subjected to partial hepatectomy (PH). Mice were given by gavage corn oil or CCl4 in corn oil for periods of 2 to 25 weeks and several mice were subjected to PH after 12 and 25 weeks of corn oil treatment. Mice were given [3H]TdR during liver regeneration and newly synthesized liver nuclear DNA was isolated and separated by BND-cellulose chromatography. Greater than 85% of the labeled DNA from PH mice eluted from BND-cellulose columns as double-stranded (ds) DNA with single-stranded (ss) regions or ends and less than 15% as ds DNA. When mice were treated with CCl4 for 8 weeks or longer a significantly greater portion of liver nuclear DNA eluted as ds DNA. Administration of HU and 5-FU with [3H]TdR decreased [3H]TdR incorporation into DNA to low levels incompatible with unscheduled DNA synthesis. Single doses of CCl4 given to mice treated with corn oil for 2 to 12 weeks provided newly synthesized DNA which was primarily (greater than 80%) ds DNA with ss regions or ends, but after 25 weeks of corn oil administration, a single dose of CCl4 resulted in newly synthesized DNA with a greater proportion of ds DNA. The high labeling of ds DNA in mice treated with CCl4 may have resulted from an alternate pathway of DNA synthesis catalyzed by the enzymes or enzyme complexes associated with semiconservative DNA synthesis or from proliferation of nonparenchymal cells with a rapid turn-over rate.

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The fidelity of mouse liver mitochondrial DNA polymerase following long-term administration of carbon tetrachloride, diethylnitrosamine, or phenobarbital.

The fidelity of liver mtDNA polymerase was compared in control mice, in mice treated chronically with diethylnitrosamine (DEN), carbon tetrachloride (CCl4), or phenobarbital sodium (PBNa). Liver mitochondria were isolated, and the mtDNA polymerase activity was obtained by high-salt extraction and subjected to chromatography first on DEAE-cellulose (DE 52) and then on heparin-Sepharose. Fidelity of the mtDNA polymerase was determined, after heparin-Sepharose chromatography, by measuring the relative incorporation of a complementary nucleotide, [32P]dTMP, and a noncomplementary nucleotide, [3H]dGMP, into acid-precipitable material with enzyme activity directed by the template-primer poly(A) . oligo(dT) 12-18. A decrease in fidelity (increase in relative incorporation [3H]dGMP) was observed after 12 or 13 weeks of treatment with DEN. The fidelity of mouse liver mtDNA polymerase also was decreased after 12 weeks of treatment with PBNa. By contrast, treatment for 12 weeks with CCl4 was accompanied either by increased fidelity (decrease in the relative incorporation of [3H]dGMP) or no change in fidelity.

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Effects of triamcinolone and of desoxycorticosterone on renal function in sheep.

Sheep were treated for 10 or 17 days with triamcinolone acetonide, 0.1 mg/kg body weight/day, or desoxycorticosterone acetate, 0.1 mg/kg body weight/day, and the results of renal function studies during hydropenia and mannitol diuresis were compared with respective control periods. GFR was increased and urine concentration was unimpaired by treatment with triamcinolone. A consistent decrease in mannitol-induced Na excretion was observed, but with large variations in the mean change, in triamcinolone treatment periods. Treatment with desoxycorticosterone resulted in an increased GFR but with impaired urine concentrating capacity. The hypokalemia produced by desoxycorticosterone was not accompanied by an increase in urinary K excretion. During mannitol diuresis in sheep treated with desoxycorticosterone, there was a significant decrease in Na excretion when compared with control periods.

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