Idiopathic diabetes insipidus in a rhesus macaque.
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Biomedical subjects
Publications and source records attributed to C D Port.
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Three Mycoplasma spp. were isolated from five colony bred laboratory dogs (Canis familiaris) obtained from a single vendor. Four of these animals were Beagles and one was a mongrel. Three displayed clinical signs of respiratory disease including dyspnea, chronic coughing and moist rales, while the other two dogs were observed during thoracic surgery to have macroscopic lesions suggestive of pneumonia. All five dogs were submitted for diagnostic necropsy during which they were cultured for bacteria and mycoplasma. Mycoplasma spp. having three distinct colonial forms were isolated from the lungs of each of the animals. These three isolates were sent to the National Cancer Institute Diagnostic Microbiology Laboratory and to the National Institutes of Health, NIAID, Mycoplasmology Laboratory. Neither laboratory could serotype these isolates against antisera to 73 Mycoplasma spp., including the common canine mycoplasmas, and nine Acholeplasma spp. Histologically, the bronchopneumonia was characterized by bronchiectasis, purulent bronchiolitis, bronchial and bronchiolar epithelial hyperplasia, chronic non-suppurative peribronchiolitis and perivasculitis, bronchiolitis obliterans, and acute to subacute purulent pneumonia. The similarity between the pathologic findings in these animals and those observed in respiratory mycoplasmosis of other species, e.g. the rat, suggests a causal relationship between the isolated mycoplasmas and the pulmonary disease observed in these dogs.
We have utilized the 6-day air-pouch model in rats to study the local tissue response to interleukin-1 exposure. Injection of either recombinant human interleukin 1 alpha (rIL-1 alpha) or interleukin 1 beta (rIL-1 beta) directly into preformed air pouches caused a 10- to 100-fold increase in the number of white blood cells present within the pouch. On a weight basis, rIL-1 beta was more active than rIL-1 alpha. Polymorphonuclear neutrophils (PMN) represented the majority of cells entering the pouch following either a single injection or repeated daily injections of rIL-1 alpha or rIL-1 beta. Significant increases in the number of mononuclear cells present were observed only following repeated injections. Repeated injections of rIL-1 beta, but not rIL-1 alpha, also caused the accumulation of large amounts of fluid within preformed pouches and a grossly apparent thickening of the connective-tissue lining of the pouch. Microscopic examination of stained sections of pouch lining tissue indicated a proliferation of the connective-tissue elements of the lining and deposition of large quantities of extracellular collagen within the pouch wall. These findings are entirely consistent with a role for interleukin 1 in the development and perpetuation of inflammatory reactions.
Bromovinyldeoxyuridine (BVDU), a substituted pyrimidine analog with antiviral activity, was given orally to beagle dogs (6/sex/dosage) at dosages of 0, 5, 12, and 30 mg/kg/day for 52 weeks. Complete physical examinations, including ECG recordings and rectal temperature measurements, and clinical laboratory determinations were performed every 13 weeks. At the end of the dosing period, 4 dogs/sex/dosage were sacrificed and complete gross and microscopic examinations performed. The remaining 2 dogs/sex/dosage were sacrificed following a 13-week recovery period. BVDU had no effect on feed consumption, respiration, body temperature, or heart rate. At 30 mg/kg, males gained less weight than controls. At 12 mg/kg (males) and 30 mg/kg (both sexes) there were slight, but statistically significant decreases in mean corpuscular volume, but no changes in red blood cell (RBC) count, hematocrit, or hemoglobin, and no evidence of reticulocytosis. In males dosed at 30 mg/kg, during the last 6 months of dosing, partial thromboplastin times, serum alanine aminotransferase, and alkaline phosphatase increased, and cholesterol decreased. Histologically, bile ductule hyperplasia and gall bladder epithelial hyperplasia were present at 12 and 30 mg/kg in both sexes at the end of both the dosing and recovery periods. At 30 mg/kg, bone marrow hypocellularity and testicular germ cell atrophy were also present in males. Thus, the liver and gall bladder are the major target organs of chronically administered BVDU in dogs. BVDU causes degenerative and proliferative hepatobiliary damage, and secondarily causes changes in clinical chemical parameters. At higher dosages, there are hypoplastic and degenerative changes in the bone marrow and testes.
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The carcinogenic potential of misoprostol, a synthetic prostaglandin E1 analogue with anti-ulcer potential, was evaluated in CD Sprague-Dawley rats. The compound was given daily by gavage at 24, 240, and 2,400 micrograms/kg, up to 150 times the daily human dose for 2 years. Necropsies were done on all animals and the incidences of non-neoplastic and neoplastic changes analyzed for significance by life table methods. The only statistically significant non-neoplastic finding was epithelial hyperplasia and hyperkeratosis of the gastric mucosa. These changes, which are characteristic of some prostaglandins, were expected. Other non-neoplastic findings were typical of known spontaneous conditions in this strain of rats. The most frequent neoplasm was the pituitary adenoma, followed by the mammary fibroadenoma, mammary adenoma, mammary adenocarcinoma, and thyroid C-cell adenoma. A rare neoplasm, squamous cell carcinoma of the ovary was found in two rats. There was no evidence that misoprostol is carcinogenic for CD Sprague-Dawley rats.
Misoprostol, a synthetic prostaglandin E1 methyl ester analogue with anti-ulcer potential, was evaluated for its carcinogenic potential in CD-1 strain mice. The compound was given daily by gavage at 160, 1,600, and 16,000 micrograms/kg for 21 months. Necropsies were done on all animals and the incidences of non-neoplastic and neoplastic changes analyzed for significance by life table methods. The only statistically significant non-neoplastic compound-related findings were epithelial hyperplasia and hyperkeratosis of the gastric mucosa and hyperostosis of bone in the marrow cavity of sternebrae and femurs. The changes in the gastric epithelium are characteristic of some prostaglandins and were expected. The bone hyperostosis was associated with misoprostol in high dosages, and was considered unique to the mouse. Other non-neoplastic findings were typical of known spontaneous conditions in mice. The most frequent neoplasm was the hepatocellular adenoma followed by lymphosarcoma, lung alveolar carcinoma, and Harderian gland adenoma. Several proliferative lesions of the duodenum were considered to be spontaneous. These were focal avillous hyperplasia, focal atypical hyperplasia, and junctional polyp. There was no evidence that misoprostol is carcinogenic for CD-1 mice.
Misoprostol, a synthetic prostaglandin E1, was administered to CD-1 mice daily by gavage for 21 months in a safety study. Hyperostosis of the marrow cavity in the sternum and femur was found predominantly in female mice of the medium (1,600 mcg/kg/day) and high dosage (16,000 mcg/kg/day) groups. Many of the mice with hyperostosis also had cystic ovaries and cystic endometrial hyperplasia indicative of hyperestrinism. It is postulated that the hyperostosis was the result not only of the effects of misoprostol but also of endogenous estrogen. Since misoprostol did not cause hyperostosis in either rats or dogs, it is probable that this effect in mice is unique.
Male rats received 25 Gy (2,500 rad) of gamma rays to the right hemithorax and were killed three or six months later. Microscopic pulmonary abnormalities developed sooner and progressed more rapidly in animals given control feed than in those given the collagen antagonist D-penicillamine (10 mg/day, p.o.). Three and four months after irradiation, hypoperfusion and radiographic hyperlucency of the right lung were observed in both the treated and control animals.
Single oral dose toxicities of six hexamethylmelamine samples with different particle size distributions were evaluated in Osborne-Mendel rats. The calculated LD50 values for the 6 samples were 1706 to 2150 mg/kg )10,236 to 12,900 mg/m2). The two samples with median particle size less than 40 micron were more toxic than the other 4 samples. Among the latter samples, severity of toxic effects was not correlated with particle size. Leukocytes, lymphocytes, platelets and body weight showed dose-related decreases for all samples. Particle size appeared to have a minimal effect on these variables. The drug produced toxic effects on rapidly proliferating tissues: lymphoid, hematopoietic and germinal epithelium. At lethal doses, microscopic lesions were lymphoid tissue hypoplasia, bone marrow hypoplasia with elevated myeloid:erythroid ratios and spermatogenic arrest. The major target organs at nonlethal doses were bone marrow and germ cells, with germinal epithelium showing the most severe lesions.
The light microscopic features of a spontaneous neoplasm of adipose tissue from a rat were suggestive of a mixed liposarcoma with a myxoid matrix. However, ultrastructurally, the cell characteristics were those of a hibernoma. These characteristics included cells containing lipid droplets of variable size, numberous pleomorphic mitochondria and close apposition to blood vessels. Lipofuscin granules and subplasmalemmal condensations were not observed ultrastructurally.
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The effects of an anesthetic agent on lung tumor induction in noninbred Syrian golden hamsters were investigated after intratracheal instillation of a benzo[a]pyrene-ferric oxide mixture. Inhalation anesthesia with ether or methoxyflurane was accomplished with a closed recirculatory system that allowed a short induction time for anesthesia and a good control over the concentration of anesthetic. This type of anesthetic induction was compared with systemic induction by Brevital. Survival rates during the 10 weekly instillations were least for the Brevital-treated group and greatest for the methoxyflurane-treated group. Body weight gain was lower in both the ether- and Brevital-treated groups as compared to the group anesthetized with methoxyflurane. The animals anesthetized with Brevital had the shortest tumor latency, but the tumor incidence during the weeks of the experiment was similar in the group treated with this agent and the group treated with ether. Exposure to methoxyflurane and the carcinogen produced a slow onset of deaths from tumors and lower tumor incidence. These results are discussed in relation to retention of the dose of carcinogen in the respiratory tract and effect of inhalation anesthia on consequent lung tissue pathology.
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Dogs and cats killed by intravenous injection of either 0.3 ml/kg body weight T-61 or 100 mg/kg body weight pentoarbital and necropsied at less than 5 minutes or at 15 minutes after injection did not have gross or microscopic pathological changes. However, dogs and cats killed with T-61 at a dose of 1.0--1.5 ml/kg body weight and necropsied at 15 minutes after injection had significant gross and microscopic pathological lesions. Grossly, the lungs were severely edematous, did not collapse, and were deep red. Microscopically, the lungs had severe pulmonary edema and endothelial necrosis. Endothelial swelling of glomerular tuft vessels was also present. These lung and kidney lesions are classified as an euthanasia artefact.
Normal lung architecture of the rat, mouse, hamster, horse, and human was compared to that of emphysematous lungs from the same species by utilizing a light microscope and a scanning electron microscope (SEM). The results obtained by SEM examination of normal and emphysematous lungs corresponded to those obtained with the light microscope. However, the SEM provided a view of alveoli and airway morphology not obtainable with the light microscope. Because of the variability in pore size and number of pores per alveolus, a pore-to-alveolus ratio was determined with the SEM on the normal lungs of the above species plus the rabbit, dog, guinea pig, and rhesus monkey. Depending on the extent of other pathways for collateral ventilation, differences in number of pores per alveolus may affect a species' susceptibility to a given mechanism in the genesis of spontaneous or induced emphysema. The small number of pores per alveolus in the rat, mouse, rabbit, and hamster suggests that they would not be responsible for emphysematous changes. Pores do appear to be involved in human and horse emphysema.
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