Combined simian hemorrhagic fever and Ebola virus infection in cynomolgus monkeys.

Simian hemorrhagic fever (SHF) virus and a new strain of Ebola virus were isolated concurrently in recently imported cynomolgus monkeys (Macaca fascicularis) being maintained in a quarantine facility. Ebola virus had never been isolated in the U.S. previously and was presumed to be highly pathogenic for humans. A chronology of events including measures taken to address the public health concerns is presented. The clinicopathologic features of the disease were abrupt anorexia, splenomegaly, marked elevations of lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase, with less prominent elevations of blood urea nitrogen, creatinine, and other serum chemistry parameters. Histologically, fibrin deposition, hemorrhage, and necrosis of lymphoid cells and reticular mononuclear phagocytes were present in the spleens of SHF and of Ebola virus-infected animals. Intravascular fibrin thrombi and hemorrhage were also present in the renal medulla and multifocally in the gastrointestinal tract. Necrosis of lymphoid and epithelial cells was occasionally noted in the gastrointestinal tract. The histopathologic findings considered specific for Ebola virus infection include hepatocellular necrosis, necrosis of the zona glomerulosa of the adrenal cortex, and interstitial pneumonia, all of which were generally associated with the presence of 1 to 4 mu intracytoplasmic amphophilic inclusion bodies. The disease spread within rooms despite discontinuation of all direct contact with animals, and droplet or aerosol transmission was suspected. Antibody to Ebola virus developed in animal handlers but no clinical disease was noted, suggesting a less virulent strain of virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term effect of 2-hydroxyethyl retinamide on urinary bladder carcinogenesis and tumor transplantation in Fischer 344 rats.

The effects of HER upon early and late stages of BBN-induced bladder cancer in rats were examined. Female Fischer 344 rats were administered HER in the diet either before and during or continuously after BBN administration and were monitored periodically for up to 2 years. The total dose of BBN was 600 mg administered over a 6-week period. In a separate experiment, the effects of HER administration to syngeneic recipients of a transplanted primary bladder cancer were examined. No effects on neoplastic development were observed as the result of HER treatment before and during carcinogen administration. However, at the 1-year sacrifice, there was a significant increase in bladder tumor incidence in the animals receiving BBN followed by continuous retinoid treatment versus animals receiving BBN only. At the 2-year sacrifice, there was a significant increase in tumor progression in the continuous retinoid group versus the animals receiving BBN alone, based upon grading and staging of tumors, although tumor incidences were not significantly different. In the transplantation experiment, more recipients (9/20 versus 2/20) receiving continuous HER had large, anaplastic tumors following 9 months of observation than did control animals. This study supports the view that retinoids should not be considered as only inhibitors of carcinogenesis, but rather as modifiers which vary in their effects depending upon factors yet to be understood.

Effects of calcium and magnesium salts on nickel subsulfide carcinogenicity in Fischer rats.

The effects of calcium or magnesium salts administered by one of three different routes on the formation of muscle tumors by nickel subsulfide (Ni3S2) in Fischer F344 rats were determined. Eleven groups of 20 weanling male rats each received a single injection of 2.5 mg (31 mumol Ni) Ni3S2 into the thigh muscles of both hind limbs (i.m.). Then the rats were fed 3% calcium acetate (CaAcet)- or 3% magnesium acetate (MgAcet)-supplemented diets for 3 and 6 months, or were injected s.c. three times weekly, with 0.16 mmol doses of CaAcet/kg/injection, or with 2 mmol doses of MgAcet/kg/injection, for 1 or 4 months. Two other groups of 20 rats were injected i.m. with 2.5 mg (31 mumol Ni) of Ni3S2 mixed with 6.2 mg (62 mumol Ca) of calcium carbonate (CaCarb), or with 6.3 mg (62 mumol Mg) of magnesium basic carbonate (MgCarb). The control groups of rats received single i.m. injections of the 0.15 M saline vehicle, 6.2 mg CaCarb, and 6.3 mg MgCarb, or s.c. injections of 0.15 M saline, or 4 mmol sodium acetate, NaAcet/kg/injection, three times weekly for 4 months. After 18 months, injection site tumors were found: (i) in 70-90% of the rats injected i.m. with Ni3S2 and fed standard diet or the diets containing CaAcet or MgAcet, with no significant differences among the groups; (ii) in 95-100% of the rats given i.m. Ni3S2 and then treated with multiple s.c. injections of saline, NaAcet, CaAcet or MgAcet, with no significant differences among the groups; (iii) in 85% of rats injected i.m. with Ni3S2 + CaCarb, and (iv) in 25% of the rats injected i.m. with Ni3S2 + MgCarb. No tumors developed in the control rats. The admixtures of CaCarb or MgCarb to Ni3S2 did not affect the mobilization of nickel from the injection site. They did, however, influence the cellular responses to Ni3S2 in early stages, from 3 days to 22 weeks, after the injection. MgCarb, unlike CaCarb, strongly decreased the necrosis and increased macrophage proliferation at the Ni3S2 injection site. It also delayed the occurrence and proliferation of histiocytic-stromal cells, and prevented the occurrence of altered myoblasts.