Systemic immune response to oral colonization.
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Biomedical subjects
Publications and source records attributed to J E Fitzgerald.
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Macrophage cooperation has been considered necessary for lymphocytes to express a variety of their differentiated functions. We attempted to characterize macrophage-lymphocyte cooperation in response to a known periodontal pathogen. Actinomyces viscosus T14V. Using adherent murine cells and subpopulations of splenocyte cultures, we assessed the effect of A. viscosus T14V fractions on lymphocyte proliferation. We determined that (i) various fractions of A. viscosus induced different proliferative responses; (ii) the physical state of the A. viscosus component determined the degree of dependence on adherent cells for proliferation; (iii) the proliferative response to supernatants of sonicated A. viscosus involved interaction among adherent cells and T and B cells; and (iv) the effects of adherent cells on the proliferative response were due to cell-to-cell interactions.
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Gemfibrozil, a novel hypolipidemic agent identified chemically as 2,2-dimethyl-5-(2,5-xylyoxy) valeric acid, was evaluated for mutagenic potential in in vitro assays with Salmonella typhimurium. For evaluation of tumorigenic potential, gemfibrozil was administered in the diet (0.30, and 300 mg gemfibrozil/kg) to groups of noninbred CD-1 mice (72/sex) and noninbred CD rats (50/sex) for 78 and 104 weeks, respectively. In the bacterial mutagenesis assays, between 100 and 2,500 microgram gemfibrozil/plate failed to induce a significant increase in revertant bacterial colonies. Neither was a mutagenic response in bacterial assays induced at concentrations up to 300 microgram of five in vivo metabolites of gemifibrozil isolated from rat urine/plate. In mice, gemfibrozil did not significantly increase the frequency or the mean latency period of tumors. In rats, the statistically significant increases in hepatocellular tumors and interstitial cell tumors of the testes were dose related. Adrenal medullary and pancreatic acinar tumors were increased in male rats but were inversely dose related. Under the conditions of this assay, gemfibrozil did not elicit a tumorigenic potential in mice and female rats. In male rats and related to the hepatocellular tumor response, the peroxisome proliferation seen did not occur in humans chronically administered hypolipidemics.
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Two patients with sarcoidosis involving pulmonary hilar lymph nodes developed the nephrotic syndrome. Renal biopsy in both cases showed membranous glomerulonephritis. In one patient, there was an associated renal vein thrombosis.
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The effect of vidarabine, a new antiviral agent, on the offspring of rats, rabbits, and monkeys was studied by varying routes of administration during several periods of gestation. Vidarabine demonstrated a dose-related teratogenic effect in rats when given parenterally at doses of 30 mg/kg and greater. The drug was also teratogenic in the rabbit at dosages of 5 mg/kg and greater by the parenteral route or when applied topically in 10% concentration to 5 or 10% of the body surface area. The pattern of malformation was similar in the two species, and consisted of multiple, severe abnormalities of the head, trunk, and limbs. The drug had no demonstrable teratogenic effect in a limited study in the rhesus monkey; nor were there adverse effects on the offspring when it was applied intravaginally to pregnant rats in the perinatal period.
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A spontaneous retinal dystrophy was found in 4 percent of Sprague-Dawley-derived rats examined. The lesion occurred both unilaterally and bilaterally in equal frequency, but the incidence in the females was 2 times greater than in males. Retinal change consisted of focal or diffuse absence of the outer layers of the retina, but frank degenerative changes or progression of the lesion was not observed. The cause of the dystrophy was not determined, but its increased occurrence with increasing age of the rats suggests an age-related lesion.
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