Abstract. Histologic, histochemical, and electron microscopic studies of generalized ceroid-lipofuscinosis in a cynomolgus monkey are presented. Histologically, a wide variety of tissue cells contained numerous bright eosinophilic intracytoplasmic granules that varied in size from 0.5 pm to 4.0 pm in diameter. Histochemically, the granules gave a weakly positive reaction with periodic acidSchiff and for lipids. They were weakly acid fast and capable of emitting autofluorescence. Ultrastructurally, the granules were single unit membrane-bound, and contained dense osmiophilic material with frequent concentric or fingerprint-type lamellar formation. The granules were different than hemofuscin, iron, and bilirubin. Tinctorially the granules were unique-they were bright red with hematoxylin and eosin and, thus, differed from typical age-related lipofuscin pigment.
Flavobacterium arborescens is a common rod-shaped, gram-negative bacterium which, when cultivated in a nutrient medium, is an efficient source of glucose isomerase (GI). GI is then used in the production of high fructose corn syrup. Studies were conducted to assure product safety and establish GRAS status for GI derived from F. arborescens. A viable cell suspension of F. arborescens and the cell-free medium in which the organism was cultured were administered i.v. to rats and rabbits. For feeding studies, the cells were immobilized using polycationic polymers and a crosslinking agent (i.e., chitosan, polyethylenimine and glutaraldehyde). GI, in the whole cell immobilized form, was offered at concentrations of 0, 1.5, 3.0 or 5.0% (wt/wt) of the diet to dogs for a minimum of 90 consecutive days and to rats over three generations. Animals were observed daily for signs of toxicosis; body weight and food consumption were monitored; biochemical tests, hematologic determinations, and urinalyses were done on blood and urine samples; and thorough gross and microscopic tissue examinations were performed at terminations. There were no signs of infection or toxicosis following i.v. administration of F. arborescens or the cell-free supernatant fluid. This, and the lack of toxicity in dogs and rats which received daily dietary concentrations of GI many times above the projected highest possible human exposure level, suggest that there should be virtually no risk of toxicity associated with the consumption of food and beverages containing high fructose syrup produced by GI derived from F. arborescens.
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