The cell cycle: a review.

The cell cycle is a complex process that involves numerous regulatory proteins that direct the cell through a specific sequence of events culminating in mitosis and the production of two daughter cells. Central to this process are the cyclin-dependent kinases (cdks), which complex with the cyclin proteins. These proteins regulate the cell's progression through the stages of the cell cycle and are in turn regulated by numerous proteins, including p53, p21, p16, and cdc25. Downstream targets of cyclin-cdk complexes include pRb and E2F. The cell cycle can be altered to the advantage of many viral agents, most notably polyomaviruses, papillomaviruses, and adenoviruses. The cell cycle often is dysregulated in neoplasia due to alterations either in oncogenes that indirectly affect the cell cycle or in tumor suppressor genes or oncogenes that directly impact cell cycle regulation, such as pRb, p53, p16, cyclin D1, or mdm-2. The cell cycle has become an intense subject of research in recent years. This research has led to the development of techniques useful for the determination of the effects of drugs and toxins on the cell cycle. Any drug or toxin with DNA damaging ability would be expected to alter cell cycle progression, and therefore, the cell cycle should be considered in the design of studies using such chemicals. With the appropriate techniques, cell cycle alterations may also be detected in tissue sections. Because of the ubiquitous nature of the cell cycle, it deserves consideration in the design and interpretation of studies in a wide variety of disciplines.

Intestinal lymphosarcoma in captive African hedgehogs.

Two captive adult female African hedgehogs (Atelerix albiventris) had inappetance and bloody diarrhea for several days prior to death. Both hedgehogs had ulceration of the small intestine and hepatic lipidosis. Histopathology revealed small intestinal lymphosarcoma with metastasis to the liver. Extracellular particles that had characteristics of retroviruses were observed associated with the surface of some neoplastic lymphoid cells by transmission electron microscopy. These are the first reported cases of intestinal lymphosarcoma in African hedgehogs.

A canine model of familial mammary gland neoplasia.

Intact female Beagles from life-span studies in the Lovelace Respiratory Research Institute colony were examined for mammary tumor incidence. The breeding colony, founded in 1963, produced five generations from 28 founder females. After proportional hazards analysis, two maternal families were shown to have markedly different phenotypes, one susceptible and one resistant to mammary neoplasia, as compared with the entire colony. When tumors were subdivided into benign and malignant based on local invasiveness, familial differences in tumor incidence were preserved for each tumor type. Fifty-seven females in the susceptible family developed 149 benign and 39 malignant tumors, and 95 females in the resistant family developed 70 benign and 20 malignant tumors. The ratio of benign to malignant tumors of about 4:1 for both families was higher than expected. Using Kaplan-Meier and log-rank analyses, the susceptible family had a 50% malignant tumor incidence by age 13.6 years, whereas the resistant family did not have a 50% incidence until 17.0 years (P = 0.0065). Because of marked censoring, Kaplan-Meier analyses could not provide an estimate of the 50% benign tumor incidence; mean incidence age was calculated instead. These estimates for benign tumors for susceptible and resistant families were 10.8 and 13.8 years (P = 0.0001), respectively. Using chi(2) tests, families had no differences in the occurrence of the types of benign (P = 0.098) or malignant (P = 0.194) tumors or in the ratio of benign to malignant tumors (P = 0.778). Immunohistochemical analysis of malignant tumors from both families did not demonstrate differences in p53 mutation rate or p185erbB-2 expression. These results suggest that 1) genetic factors produce familial differences in the age of onset of both benign and malignant mammary tumors; histologic types do not segregate by family; 2) the ratio of benign to malignant tumors is greater than formerly reported; and 3) neither p53 nor p185erbB-2 alterations are the basis for the familial predisposition.

Hepatic coccidiosis associated with hepatic necrosis in a goat.

Hepatic coccidiosis, usually caused by a member of the genus Eimeria, is common in rabbits but rare in other mammals. We describe the first reported case of naturally occurring hepatic coccidiosis in a goat. An approximately 6-month-old crossbred goat was presented with a history of diarrhea for 1 week and death. The liver had grossly visible, coalescing foci of necrosis measuring up to 6 cm in greatest dimension. Microscopically, areas of coagulative necrosis also had ectatic and hyperplastic bile ducts that contained coccidial meronts, macrogamonts, and microgamonts within the cytoplasm of epithelial cells. Bile duct lumina contained scattered oocysts. Fibrosis and aggregates of lymphocytes surrounded affected ducts. Microscopic and ultrastructural characteristics of coccidian stages were compatible with the genus Eimeria, but the species could not be determined. The small intestine also had coccidiosis; however, it was unclear whether or not the same coccidian species affected both the liver and the intestine.