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An apparently normal, non-tuberculin-reacting, splenectomized owl monkey presented tuberculosis-like lesions of the lung at necropsy. Histological and bacteriological examination failed to demonstrate the presence of acid-fast organisms. Retrospective inquiry showed the animal had been inoculated using complete Freund's adjuvant during a malaria vaccine trial. Lesions observed were compatible with lipid embolism of the adjuvant in the lungs.

Five tamarins (four Saguinus mystax and one S. labiatus) died with wasting syndrome characterized by chronic diarrhea at the Center for Reproduction and Conservation of Non-Human Primates in Iquitos, Peru. At necropsy, the terminal ileum of all affected tamarins was found to be markedly thickened. Histologically, the terminal ileal mucosa was completely ulcerated, and effaced by debris and mononuclear inflammatory cells. The submucosa and serosa were thickened by fibroplasia, mononuclear cell infiltrates and variable edema. No infectious agent was observed. The lesions were similar to those described previously for Crohn disease. This is to our knowledge the first report of terminal ileitis resembling Crohn disease in non-human primates.

This chapter deals with the history of agroterrorism, biological crimes, and biological warfare directed toward animal agriculture, specifically horses, cattle (both beef and dairy), swine, sheep, goats, and poultry. A recent investigative report concludes that it was an ambitious and well-planned program, conducted on three continents, but that the success of the attacks was questionable. In a very recent excellent investigative report on the introduction of rabbit calicivirus disease into New Zealand, Steve Goldstein offers a serious, thorough review of agroterrorism and biological crimes. The animal pathogens and the species affected that are most often mentioned as being the most important as potential agroterrorism attack agents are, for cattle, foot-and-mouth disease virus and rinderpest virus; for swine, foot-and-mouth disease virus, classical swine fever virus, and African swine fever virus; and for poultry, avian influenza virus and Newcastle disease virus. With U.S. government funding and attention focused on countering biological weapons targeted at humans, agencies and groups are just now becoming aware of the threat posed by agroterrorism and biological warfare directed against the nation's animals and crops. The current laws that authorize investigations of potential terrorism rest on assumptions that may be misaligned for preventing and punishing agroterrorism. The biocrimal acts and the consequent economic impact clearly demonstrate that agriculture can be the target of an economically devastating terrorist or criminal attack.

The reproduction performance of captive owl monkeys, a breed used extensively in biomedical research, was observed at the Battelle Primate Facility (BPF). The colony grew through captive breeding, imports from the Peruvian Primatological Project, and others to a peak size of 730. It included seven karyotypes of Aotus sp. Results showed that owl monkeys can breed successfully in a laboratory in numbers sufficient to sustain modest research programs. Reproductive success increases when pairs are compatible, of the same karyotype, and stabilized; however, mated pairs of different karyotype are also productive. Under conditions of controlled lighting and heating, owl monkeys at BPF showed no birth peak nor birth season.

The distribution and effects of inhaled {sup 239}Pu(NO{sub 3}){sub 4} deposited in the liver of dogs were studied in five groups of 20 beagles exposed to initial lung depositions ranging from 1.0 to 520 Bq g{sup {minus}1} lung. Following life-span observations, the liver contained 40 {plus_minus} 1% of the final body deposition of plutonium, second only to the skeleton. The liver-to-skeleton ratio of deposited plutonium for total organ was 0.8, or 3.5 when expressed on a per-gram basis. There was no effect of exposure level on liver-to-skeleton rations. Autoradiographs showed that the dose rate delivered to parenchymal cells was higher than evident from radiochemical analysis of the whole organ. Elevated levels of serum liver enzymes were observed in groups with mean iver concentrations of 1.3 Bq g{sup {minus}1} and liver doses of 3 Gy or higher. Nodular hyperplasia of liver and bile-duct hyperplasia were observed. Liver tumors, principally of bile-duct epithelium, were late-occurring and were observed at lower exposure levels at which life span was not shortened by lung or bone tumors. 26 refs., 5 figs., 3 tabs.

Gross and light microscopic features of testicular neoplasms were examined in the male beagle dog used in three studies to examine the life-span effects of inhaled plutonium (Pu). One hundred and sixty-six cases of testicular neoplasia (TN) occurred among 105 dogs that ranged in age from 7.5 to 17.7 years at the time of diagnosis. The 166 cases of TN comprised 113 interstitial cell tumours, 27 seminomas in situ, 19 seminomas, and seven Sertoli cell tumours. Serum testosterone and estradiol 17-beta concentrations, and the serum testosterone-to-oestradiol ratio were determined in 39 dogs with TN and in five clinically normal, sexually intact, age-matched cohorts. Serum hormone concentrations did not differ significantly among tumour types or between dogs with neoplasms and age-matched cohorts. There was a significant relationship between initial lung deposition (ILD) of Pu and activity in the testis (Bq/g testis). The slope of the relationship was 0.35, 0.89 and 0.91 for 239PuO2, 238PuO2 and 239Pu(NO3)4 respectively. Pu in the testis at long times (5 years) after inhalation was between 0.0001 and 0.03% ILD, depending on the physicochemical form of Pu. Although the mean activity of Pu in the testis of dogs was higher in those life-span studies employing 238PuO2 and 239Pu(NO3)4, the cumulative proportion of dogs with tumours, the distribution of tumour types, and mean time to first tumour was not significantly different among the three studies or dose groups, including controls, within a study.

The activity of three urinary enzymes, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and N-acetyl-beta-D-glucosaminidase (NAG), was evaluated in 71 adult owl monkeys. Fifty-six animals had normal renal function, while 15 had evidence of renal dysfunction. Urinary enzyme: urinary creatinine ratios (UE: UCr) were also determined. The activity for NAG was similar to that of other species, while ALP and AST were higher. Regression analyses revealed that urinary enzymes and UE:UCr were significantly correlated (P < or = 0.0001) with indices of renal damage and could identify active renal disease.

A two-phase study was initiated to delineate the peripheral blood lymphocyte populations present in owl monkeys and to correlate those populations with immune response and parasitism during malaria infection. The goal of phase I of the study was to elucidate a monoclonal antibody panel that could be used to characterize peripheral blood mononuclear cell (PBMC) populations with flow cytometric techniques. Forty-two monoclonal antibodies (reported to be reactive with human and macaque lymphocyte antigens) were screened for activity to owl monkey PBMC. Eleven monoclonals were found to react: anti-H42A (MHC Class II DP-like); anti-TH14B (MHC Class II DR-like); and anti-TH81A5 (MHC Class II DQ-like); anti-H58A (MHC Class I); anti-DH59B (granulocyte and monocyte); anti-B1 (B cell); anti-T4 (CD4); anti-Leu3a (CD4); anti-Leu11a (CD16); anti-60.3 (CD18); and anti-OKM1 (NK and monocyte). In a preliminary retrospective study correlating antibody titers, parasitemia values, and MHC Class I and Class II marker profiles on PBMC to test antigens used in malaria vaccine trials, a significant negative association was observed between cells bearing MHC Class II molecules and the other elements of the comparison. In summary, an appropriate panel of monoclonal antibodies has been identified for characterizing PBMC in owl monkeys, and preliminary studies indicate a possible association between clinical outcome and expressed phenotypic PBMC markers.

Impaired renal function was observed in sixteen Aotus nancymai 25 and 3 months following infection with the Uganda Palo Alto strain of Plasmodium falciparum. Decrease were noted in the clearance of endogenous creatinine, creatinine excretion, and urine volume while increases were observed in serum urea nitrogen, urine protein, urine potassium, fractional excretion of phosphorus and potassium, and activities of urinary enzymes. The results were suggestive of glomerulonephropathy and chronic renal disease.

The excretion of urinary protein was evaluated in 62 owl monkeys using timed urine collections. The ratio of urine protein to urine creatinine concentrations (Up/c) was determined for each monkey. Linear regression analysis was used to calculate the correlation between that ratio and urine protein (mg/dl) and 24-hour urinary protein loss (mg/kg). The coefficient of determination for Up/c to urine protein and 24-hour urinary protein loss was significant (P less than or equal to 0.0001). Determination of the Up/c in a urine specimen was found to be an acceptable diagnostic technique for detection and quantitative estimation of proteinuria.

Serum samples from 62 owl monkeys were analyzed to determine concentrations of creatine kinase activity and isozymes. Fifty monkeys were determined to be clinically normal, while twelve had cardiac disease. Findings showed that the data had a non-normal distribution. Based on nonparametric tests, significant differences were not observed between sexes or animals with and without cardiac disease, indicating that CK activity and isozymes are not reliable indicators of myocardial disease in the owl monkey. Reference values presented are only intended as a guide. Each laboratory should determine its own reference values.

The Battelle Primate Facility houses one of the largest collections of neotropical primates in the United States. The facility is a research resource for undergraduate and graduate students. Battelle staff, as well as staff and faculty from U.S. and international institutions. Researchers have access to the animals for a variety of studies encompassing several disciplines, a large collection of preserved tissues, and an extensive biomedical database. The facility is a World Health Organization Collaborative Center for Clinical Pathology of Neotropical Primates and is involved with the Peruvian Primatological Project in Iquitos, Peru, which provides opportunities for research in primatology and conservation.

Four hundred and fifty wild-caught owl monkeys (Aotus nancymai) were shipped from Iquitos, Peru to Richland, Washington. Mortality and body weight changes from the time of shipment to 30 days after arrival were evaluated using age, sex, and transit time as comparison criteria. No association between mortality and sex, age, or transit time was observed. The mortality percentage from shipment to 30 days after arrival was 2.44%. Both age and transit time had a significant effect on weight changes, but sex did not. Shipping procedures are described.

The purpose of this study was to determine serum reference values for creatine kinase (CK), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in captive-born and wild-caught owl monkeys to assess their usefulness for diagnosing myocardial disease.Blood samples were collected for CK, AST and LDH determinations. In addition, urine samples were collected and semiquantitative tests performed.There was no statistically significant difference between CK, AST and LDH when comparing both groups. However, when comparing monkeys with proteinuria to those without proteinuria, a statistically significant difference in CK value was observed (P = 0.021). In addition the CK/AST ratio revealed that 29% of the animals included in this study had values suggesting cardiac infarction. Grossly, cardiac concentric hypertrophy of the left ventricle and small, pitted kidneys were the most common findings. Microscopically, myocardial fibrosis, contraction band necrosis, hypertrophy and hyperplasia of coronary arteries, medium-sized renal arteries and afferent glomerular arteriolae were the most significant lesions, along with increased mesangial matrix and hypercellularity of glomeruli, Bowman's capsule and peritubular space fibroplasia.These findings suggest that CK, AST and LDH along with urinalysis provide a reliable method for diagnosing cardiomyopathies in the owl monkey. In addition, CK/AST ratio, proteinuria and the observed histological and ultrastructural changes suggest that Aotus vociferans suffer from arterial hypertension and chronic myocardial infarction.

An adult male owl monkey (Aotus nancymai) had hypercalcemia associated with a disseminated case of histoplasmosis (Histoplasma capsulatum var. capsulatum). Histopathologic examination of tissues at necropsy showed moderate to marked numbers of small granulomas involving multiple organs. The granulomas contained numerous round, basophilic, intracellular structures, 1-2 microns in diameter, that stained positive in Periodic acid-Schiff and Gomori's methenamine silver tests. The hypercalcemia in this case was attributed to enhance conversion of dietary vitamin D to 1,25-dihydroxycholecalciferol by the granulomas.

A wild-caught male Aotus vociferans died spontaneously during quarantine. Histologic examination of the heart showed several small myocardial arteries replaced with fibrinoid necrosis and adjacent inflammation that included lymphocytes and large histiocytic cells. Less often, similar inflammatory foci were observed in the myocardium interstitium. The lesions observed in the heart of the owl monkey resembled Aschoff bodies.

A case of successful survival of twins in a Karyotype I (2n = 54) night monkey (Aotus nancymai) is described. Monthly weights of the pregnant female, and of the twins, are compared to those of pregnant females and their single birth offspring of the same sex and karyotype.

Single-strand conformational polymorphism (SSCP) analysis and direct sequencing methods were used to examine lung tumors derived from a cohort of beagle dogs with inhalational exposures to 239PuO2. These exposures were done at Pacific Northwest Laboratories where 18-month-old beagle dogs were given 239PuO2 by single-dose inhalation and allowed to live out their life-spans. Formalin-fixed paraffin-embedded blocks of tissues from 25 dogs exposed to 239PuO2 by aerosol inhalation which later developed lung tumors were available for this study. Two of 25 tumors had mutations within exon 1 of K-ras detected by SSCP analysis. Both mutations were GGT to GAT transitions at codon 12 confirmed by direct sequencing experiments. One was an adenocarcinoma from the medium-high exposure group and the other was a broncheolo-alveolar carcinoma from the medium-low exposure group. The rate of K-ras mutations in plutonium-induced lung tumors described herein (8%) was greater than previously described in canine plutonium-induced lung tumors (0%), but was less than that which we have described in spontaneous canine lung cancer (16%), less than that reported for human spontaneous non-small cell lung cancer (13–36%) and less than that described in rats with spontaneous lung cancer (40%) or lung tumors following 239Pu inhalation exposure (46%).

Publisher Summary This chapter discusses neoplastic and proliferative disorders in nonhuman primates. The chapter also provides an overview of neoplasia in nonhuman primates for veterinary practitioners, laboratory animal veterinarians, and scientists concerned with the clinical management of the diseases and the comparative aspects of oncology. Neoplasms are classically divided into two primary groups: benign and malignant. The classification of neoplasia is based on many different criteria such as histogenesis, histological features, and biological behavior. The etiology of neoplasms in nonhuman primates is largely unknown, although several contributory causes have been identified in different species, including genetic factors, ionizing radiation, chemical carcinogens, and viruses. The development of neoplasia is a multistep process involving the clonal evolution of abnormal cell populations that gain a selective growth advantage over normal cells by accumulating specific alterations in at least two groups of genes: protooncogenes and tumor-suppressor genes. A description of various tumors—tumors of the skin, soft tissues, and bones; tumors of the cardiovascular system; tumors of lymphoid and hematopoietic systems; and tumors of the respiratory organs—is also provided in the chapter.

Of the 232 tamarins (133 Saguinus mystax and 99 Saguinus labiatus) that died at the Center for Reproduction and Conservation of Nonhuman Primates in Iquitos, Peru from January 1987 to December 1990, 23 monkeys (9.9%) were diagnosed as having chronic colitis. Typically, the cecal and colonic mucosa was greyish and small yellowish cysts, measuring 1-4 mm, were found randomly distributed bulging the mucosa. Microscopically, colitis cystica profunda was diagnosed additionally in six more animals, giving a total of 29 cases (12.5%). This is the first report to our knowledge that describes colitis cystica profunda in a nonhuman primate.

Serum and urine analytes were compared between adult wild-caught and adult colony-born owl monkeys (Aotus nancymae), to determine if normative clinical pathology data were similar. Significant differences (P < or = 0.05) were noted in serum protein, glucose, sodium, urine calcium, calcium clearance, and fractional clearance of calcium between the two groups. The results suggest that reference data for feral owl monkeys is not completely applicable to colony-born animals, however, the differences are too small to be of clinical significance.

Humans with inherited abnormalities of hemoglobin (Hb) synthesis have less frequent and less severe infections of malaria. This study sought to determine if karyotypic variation in the owl monkey was expressed as differences in Hb moieties and if it offered a selective advantage in susceptibility to malaria. Five karyotypes of owl monkey were evaluated on the basis of the electrophoretic mobility of their major and minor Hb components. The results of 40 owl monkeys of different karyotypes demonstrated that statistically significant differences exist among karyotype I animals and those with karyotypes II, III, and V, particularly with regard to their HbA2 concentrations. This finding is of interest in light of the fact that karyotype I animals are considered to be less susceptible to infection with human strains of Plasmodium falciparum than karyotypes II, III, and V, which are viewed as being highly susceptible.

The effects of inhaled 238PuO2 deposited in the liver of dogs were studied in beagles exposed to initial lung depositions ranging from 5.7 to 2979.7 Bq/g lung. Approximately 20% of the initial lung deposition was translocated to the liver by 1500 days after exposure. Life-span observations revealed that the liver contained 40% of the final body burden of plutonium, second only to the skeleton. Elevated serum liver enzyme activities were observed in dogs with final liver depositions of >0.4 Bq/g, cumulative dose to the liver of >0.18 Gy and annual dose rate 20.02 Gy/year. Enzyme elevations were seen at one dose level lower than that in which bone or lung tumors were observed. Linear regression analysis revealed strong to moderate correlation between cumulative dose and dose rate and time to observed increases in liver enzyme activities. Liver tumors were late-occurring neoplasms observed at lower exposure levels where life span was not shortened by lung and bone tumors. @ 1995 by Radiation Research Society

Thioguanine-resistant primary clones were grown from single cell suspensions obtained from dog and human kidneys by enzymatic digestion. In medium containing a relatively high concentration (10 micrograms/ml) of thioguanine, thioguanine-resistant primary clones arose from each source at frequencies ranging from 10(-4) to 10(-5). A reduction in total hypoxanthine uptake was found in the thioguanine-resistant primary clones which had developed in thioguanine medium, consistent with a reduction in hypoxanthine phosphoribosyltransferase activity. When these thioguanine-resistant primary clones were subsequently grown in the absence of thioguanine and assayed for the thioguanine-resistant phenotype and hypoxanthine phosphoribosyltransferase activity, it was found that most were now thioguanine-sensitive and yielded cell-free extracts with substantial amounts of hypoxanthine phosphoribosyltransferase activity. In contrast, thioguanine-resistant human clones grown continuously in the presence of thioguanine yielded cell-free extracts with little or no detectable hypoxanthine phosphoribosyltransferase activity. Southern blot analysis demonstrated no structural alterations in the hypoxanthine phosphoribosyltransferase gene in thioguanine-resistant primary human kidney clones. These results suggest that a novel mechanism(s) for thioguanine resistance and the control of hypoxanthine phosphoribosyltransferase expression may occur in dog and human kidney cells.

A wild-caught adult female Saguinus mystax died after 54 months in captivity. At necropsy, a small reddish zone in the renal cortex of one kidney was shown histologically to be a hemangiosarcoma.