David H. Gribble

Nontuberculous Mycobacterial Disease In Rhesus Monkeys

In a colony of rhesus monkeys (Macaca mulatta), 42 cases of nontuberculous mycobacterial-related disease were identified from 1970 to 1978. The disease affected young and old colony-born and wild-caught monkeys of both sexes. Serotypes 1, 2, 4, 8, and 18 of the Mycobacterium avium-intracellulare group were isolated from different monkeys. The lesions were primarily intestinal in 36 monkeys. Lesions of the large intestine, small intestine, and mesenteric lymph nodes were characterized by diffuse accumulations of large macrophages containing many acid-fast bacteria. Acid-fast bacteria could not be identified histologically in four monkeys with typical histories of diarrhea and weight loss, positive skin reactions to the tuberculin test with M. avium tuberculin, and isolation of the organism from tissues on one or more occasions. Two monkeys had histologically positive lesions limited to the lungs, although chronic colitis of undetermined cause was present.

Plasmodium knowlesi Malaria in the Rhesus Monkey

Twelve Rhesus monkeys were inoculated intravenously with about 500 000 malaria parasites, Plasmodium knowlesi. Acute hemolysis occurred 5 days later, and all animals died on the 6th or 7th day after inoculation. All organs were gray-green to gray-brown because of deposition of hemoglobin and malaria pigments. This deposition was particularly striking in the lung, brain, abdominal fat and serous surfaces. Microscopic changes indicative of acute hypoxia were found in the liver (centrilobular necrosis) and kidneys (acute tubular necrosis). Terminal intravascular coagulopathy was evidenced by widely distributed, recently formed, fibrin thrombi.

Transmission of Creutzfeldt-Jakob Disease to the Stumptail Macaque (Macaco arctoides)

Summary The successful transmission of Creutzfeldt-Jakob disease from both affected human and chimpanzee brain to stumptail macaques has been accomplished. The incubation period of 5 yr was the same for both animals; however, the course of the disease was longer in the animal receiving the human brain. In both cases, initial mild symptoms slowly remitted only to reappear some 4 mo later. Muscle biopsies revealed changes suggestive of a mild neuropathy. In addition, there appeared to be an increased ability to incorporate 3H-thymidine in untreated cultures of lymphocytes from peripheral blood.

Distribution and binding of radioactivity in the starling after intravenous administration of [14C]3-chloro-p-toluidine

Abstract Ring labeled avicide [ 14 C]3-chloro- p -toluidine HCl (CPT) was injected (14.7 μCi) by intravenous route to starlings. The radioactivity was found to be unevenly distributed in different parts of the body. The retention half-life of radioactivity in brain, spleen, heart, and bone marrow was approximately similar to that of the plasma and ranged from 3–6 hr. A longer retention of radioactivity (8–14.6 hr) than that of the plasma was found in the muscle, lung, liver, and kidney. Of the nine tissues examined, a substantial amount of [ 14 C]CPT radioactivity was found covalently bound only to liver and kidney proteins. The extent of covalent binding to kidney protein always exceeded the binding to liver protein. Microscopic examination of liver and kidney sections prepared from the birds 12 hr after [ 14 C]CPT injection revealed marked histopathological changes in the liver and somewhat less striking changes in the kidney. The changes in liver were vacuolation and varying degrees of necrosis ranging from focal to diffuse. In kidney, the pathological changes included hyaline granularity of the cytoplasm. Pretreatment of birds with a microsomal enzyme inducer, phenobarbital, or tissue glutathione depletor, diethylmaleate, had no effect on covalent binding of [ 14 C]CPT radioactivity to liver protein. These pretreatments, however, enhanced the binding significantly to kidney protein without producing any significant effect on kidney pathology. SKF 525A in phenobarbital pretreated birds had a marked inhibitory effect on covalent binding of [ 14 C]CPT radioactivity to liver protein. Various explanations have been offered to account for the discrepancy regarding the lack of a positive correlation between the extent of covalent binding of [ 14 C]CPT radioactivity and tissue lesion in starlings. It has been postulated that an hydroxylamine metabolite of the parent compound possibly binds to liver protein and is responsible for hepatic necrosis.

Urinary excretion of beta-glucuronidase after administration of neomycin to rats: A preliminary report☆

Abstract Increased beta-glucuronidase was excreted in the urine of female Fischer rats which had been given varying doses of neomycin by im injections. Results showed that there was a correlation between the observed histopathologic changes in the renal tubules and the activity of beta-glucuronidase measured in the urine. It would appear that urinary β-glucuronidase activity may represent a sensitive index of tubular damage produced by nephrotoxic drugs.