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Root canal procedure for disarming nonhuman primates.

Nonhuman primates were disarmed by shortening their canine teeth. These teeth were cut off near the gingival level, the entire pulpal tissue removed and the canal filled with a formulated paste which was radiopaque, adhesive and germicidal. The teeth were sealed with a commercial alloy. This endodontic procedure was a quick, practical one-step method for permanently disarming nonhuman primates.

Animals

Tuberculosis in nonhuman primates as a threat to humans.

Nonhuman primates are used in many laboratories either as modest systems for studies of disease processes or as a source of these tissues for cell culture and vaccine production. Much too frequently, the health of these donor animals is taken for granted, although T.B. testing is one of the few procedures routinely performed. In spite of this screening, outbreaks of T.B. among various simian species are still sufficiently commonplace to make maintenance and use of these animals a continuing source of danger to the human population. Development of rampant fatal tuberculosis in established colony animals (chimpanzees, baboons, others) previously tested as tuberculin negative suggests the need for continuing monitoring as well as extreme caution in handling of these animals, especially at necropsy. Further, use of complete Freund's adjuvant or isoniazid either experimentally or therapeutically will obscure the interpretation of the skin test. Present lack of concern by many investigators for biohazards associated with use of nonhuman primates makes the problem of laboratory-associated infections a major source of concern. Positive conversion of animal handlers has occurred a sufficient number of times to make development of tuberculosis in a colony of animals a matter of more than academic interest.

Animals

Urinary metabolites of 2, 5, 2', 5'-tetrachlorobiphenyl in the nonhuman primate.

The metabolism of 2, 5, 2', 5'-tetrachlorobiphenyl (TCB) in nonhuman primates was found to be different from that previously reported in lower species. Monohydroxy TCB (I), the only metabolite in the ether extracts of rat urine, is a minor metabolite in the urine of nonhuman primates. The two major metabolites identified in the urine were dihydroxy TCB (II) and trans-3,4-dihydro-3,4-dihydroxy TCB (III). A second minor metabolite was identified as hydroxy-3,4-dihydro-3,4-dihydroxy TCB (IV). None of the above mentioned metabolites have been reported in primates and only I and III have been identified in lower animals. It is concluded that a likely mechanism for metabolism of TCB in primates is through arene oxide intermediates. This observation is of particular importance in that these types of intermediates are known to alkylate cellular components causing carcinogenic, mutagenic, necrogenic and teratogenic effects.

Animals

Nonhuman primate models of toxemia of pregnancy.

Hypertension in the nonpregnant and pregnant nonhuman primate is not found frequently by research investigators. Its incidence is probably infrequent. No well-defined clinical syndrome analogous to toxemia of human pregnancy has been described. The experimental induction of the disease in pregnant nonhuman primates has been difficult. Although there would be an important role for such an animal model, its discovery does not appear imminent.

Animals

Implantation of cranial base metallic markers in nonhuman primates.

Cranial base metallic markers are useful in growth and developmental research on the nonhuman primate model. Metallic implants aid in superimposing serial cephalometric roentgenograms in the study of craniofacial changes. They also enable measurement of linear and angular changes in the cranial base. The design of a special implant gun is described in detail. A suggested technique for placement of tantalum markers in the cranial base of nonhuman primates is discussed.

Animals

Induction of osteogenic sarcomas and tumors of the hepatobiliary system in nonhuman primates with aflatoxin B1.

The carcinogenicity of aflatoxin B1 (AFB1) has been under evaluation in nonhuman primates for the past 13 years. A total of 47 Old World monkeys, chiefly rhesus and cynomolgus, have received AFB1 i.p. (0.125 to 0.25 mg/kg) and/or p.o. (0.1 to 0.8 mg/kg) for 2 months or longer, and 12 are currently alive and without evidence of tumor. Thirteen of the 35 monkeys necropsied to date (37%) developed one or more malignant neoplasms, yielding an overall tumor incidence of 28%. Five of the neoplasms were primary liver tumors (2 hepatocellular carcinomas and 3 hemangioendothelial sarcomas), and 2 cases of osteogenic sarcoma were found. Other tumors diagnosed were 6 carcinomas of the gall bladder or bile duct, 3 tumors of the pancreas or its ducts, and one papillary Grade I carcinoma of the urinary bladder. The tumors developed in animals receiving an average total AFB1 dose of 709 mg (range, 99 to 1354 mg) for an average of 114 months (range, 47 to 147 months). Fifteen of the 22 necropsied monkeys (68%) without tumor showed histological evidence of liver damage, including toxic hepatitis, cirrhosis, and hyperplastic liver nodules. These animals had received an average total AFB1 dose of 363 mg (range, 0.35 to 1368 mg) for an average of 55 months (range, 2 to 141 months). Our results indicate that AFB1 is a potent hepatotoxin and carcinogen in nonhuman primates and further support the hypothesis that humans exposed to this substance may be at risk of developing cancer.

Aflatoxins

Stimulus similarity and order as factors in visual short-term memory in nonhuman primates.

The short-term retention of nonhuman primates for a single sample or for two successively presented samples was assessed in four delayed matching-to-sample experiments with delays of .03, 4, 8, 16, and 32 sec. The single sample tasks included one (Experiment 1) or two (Experiment 4) distractor stimuli in the choice set (matching test). In the two successive samples tasks, the animals matched (reconstructed) the order of presentation of two samples with (Experiment 3) and without (Experiment 2) a distractor stimulus. Also, the possible combinations of eight stimuli (four colors and four shapes) were arranged to test the effects of sample set and choice set similarity. Taken together, analyses of the errors indicated that both sample and choice set similarity were significant sources of confusions in delayed matching. Order errors occurred independently of similarity but were a source of forgetting primarily at the longest delays (16 and 32 sec). Two exceptions to the similarity effect (second response errors in Experiment 3 and errors of an inexperienced group in Experiment 4) were observed. Possible reasons for the exceptions and several implications of these findings for theories of short-term memory are discussed.

Animals

Experimental biharzial bladder cancer: tryptophan metabolism in nonhuman primates experimentally infected with Schistosoma haematobium.

A nonhuman primate species infected with Schistosoma haematobium provided a model system for controlled studies on biharzial bladder cancer. Urinary excretion of tryptophan metabolites by capuchin monkeys (Cebus apella) was similar to that of humans when expressed per g creatinine. Liver tryptophan oxygenase activity of the capuchin monkeys was comparable to that of humans. Excretion of 3-hydroxykynurenine and 3-hydroxyanthranilic acid was elevated above control levels in capuchin monkeys infected experimentally with S. haematobium. The capuchin-S. haematobium system closely resembles the human biharziasis system and offers a reproducible laboratory model system for the controlled study of the parasitology, pathogenesis, and biochemistry of biharzial bladder cancer.

3-Hydroxyanthranilic Acid

Progress in rhesus histocompatibility typing resulting from the Second International Nonhuman Primate Histocompatibility Workshop (1973).

The Second International Nonhuman Primate Histocompatibility Workshop permitted comparison of rhesus monkey alloantisera developed in various laboratories on a single common panel of related and unrelated monkeys. Analysis of the data permits the conclusion that at least nine specificities are recognized by more than one laboratory, including six at the first locus and three at the second locus.

Animals

Intrauterine infections in nonhuman primates.

Gross and histologic examination of five nonhuman primate placentas revealed inflammatory processes, either of the ascending type, with chorioamnionitis and fetal vasculitis, or of the hematogenous type with villitis. These reactions were similar to those occurring in man, with known implications for perinatal outcome.

Animals

Characteristics of Tuberculosis Tests Performed during Postimport Quarantine of Nonhuman Primates, United States, 2021 to 2024.

Screening nonhuman primates (NHPs) for tuberculosis (TB) is important to protect the health of NHP colonies and people who interact with them. Screening is especially important for imported NHPs from countries where TB is prevalent and biosecurity practices may be lax. There are a variety of testing methods available for TB screening and diagnosis in NHPs; all have limitations, and their performance in different settings is incompletely characterized. The US Centers for Disease Control and Prevention (CDC) collects TB testing results as part of its regulatory oversight of NHP importation. We collated the results of tuberculin skin tests (TSTs), interferon-γ release assays (IGRAs), multiplexed fluorometric immunoassay (MFIA), Mycobacterium tuberculosis complex PCR, staining for acid-fast bacilli (AFB), and culture of bacteria from tissues for imported NHPs in CDC-mandated quarantine during fiscal years 2021 to 2024. We used these data to assess test performance and intertest agreement for the different tests used. Among 107 imported NHPs tested, TST and IGRA were the most common antemortem tests performed, but they agreed poorly with each other and with culture. AFB staining and PCR exhibited moderate agreement and high positive predictive values using culture as the gold standard. The most commonly affected tissues were lungs and tracheobronchial lymph nodes, regardless of the Mycobacterium sp. identified. Further research is needed to identify and validate additional methods for TB testing in NHPs, particularly for antemortem screening. Tissue acid-fast staining and PCR exhibited high positive predictive values and could be useful to inform policies and clinical decisions about colony management and occupational health while awaiting culture results.

AFB, acid-fast bacilli

Poxvirus in West African nonhuman primates: serological survey results.

Ten species of nonhuman primates in West African habitat were analysed for variolavaccinia subgroup haemagglutination-inhibition (HI) and neutralization antibodies. The animals were taken in 27 different sampling zones in parts of the Ivory Coast, Mali, and Upper Volta. Of the 195 tested, 15 (8%) had elevated HI antibodies after nonspecific reactions were reduced with potassium periodate pretreatment. Positive neutralization antibodies were found in 21% (44 of 206). Antibodies were detected in serum from monkeys living near two areas where monkeypox cases in humans had occurred. Four samples were tested for monkeypox specific antibodies using an indirect immunofluorescent test; 3 were positive. Despite the prevalence of poxvirus antibodies in monkeys (and other animals) in West Africa, smallpox eradication has been maintained in the area since 1970; thus, animal reservoirs of poxvirus appear to pose no threat to the worldwide smallpox eradication programme.

Africa, Western

Hydatid disease in four nonhuman primates.

Hydatid disease was detected in 4 nonhuman primates (Galago crassicaudatus, Lemur catta, and 2 Macaca mulatta) at the Oregon Regional Primate Research Center. Involvement extended from 2 1/2 to 7 1/2 years. A 6-cm cyst was surgically removed from the thoracic cavity of 1 macaque; 6 years later multiple cysts were found in its abdominal cavity. Lesions found in the primates at necropsy included compression or displacement of the lungs, hydroureter and hydronephrosis, and distension of the abdomen--all related to impingement of developing cysts.

Abdomen

Failure of left atrial distension to alter renal function in the nonhuman primate.

Experiments were undertaken to determine the influence of increasing left atrial pressure on renal function in the nonhuman primate. Significant elevations of left atrial pressure, produced by using an intra-atrial balloon, had no effect on salt or water excretion, renal plasma flow, or glomerular filtration rate. There were no significant changes in heart rate or blood pressure. We conclude that, unlike those in the dog, atrial receptors in the nonhuman primate play little or no role in modulating salt and water excretion.

Animals

Antigenic similarities to HCG subunits among chorionic gonadotropins of nonhuman primates.

Comparison of antigenic similarity between human chorionic gonadotropin (HCG) subunits and the chorionic gonadotropins of six species of nonhuman primates indicates marked similarity of antigenic determinants between both subunits of HCG and the chorionic gonadotropins of chimpanzees, gorillas, and orangutans. Antisera to HCG subunits (alpha or beta) did not cross-react with the chorionic gonadotropins of baboons, macaques, or marmosets. Because of the relative availability of chimpanzees for laboratory studies, we suggest that chimpanzees may be the optimal nonhuman primate model for determining the advisability of vaccinations in man using conjugates of HCG fragments to achieve fertility control or for suppression of HCG-producing neoplasms.

Animals

Nonhuman primate models for lymphoma, leukemia, and other neoplasms.

Herpesvirus saimiri (HVS) is an oncogenic virus for a variety of nonhuman primates. HVS does not produce overt disease upon inoculation in the natural host (squirrel monkey) but consistently induces neoplasms including lymphomas and lymphocytic leukemias in 4 other species of monkeys. Various drugs inhibit replication of HVS in vitro including cytosine arabinoside and adenine arabinoside. In addition, the lymphoma and leukemia induced in owl monkeys responds to vincristine and prednisolone, cyclophosphamide, cytosine arabinoside, and human interferon. Of the various chemical carcinogens studied, the antitumor agent procarbazine induces neoplasms in a variety of species including monkeys. Thus far this compound has induced acute myelogenous leukemia (AML), lymphoma, and hemangiosarcomas in macaques. We have induced primary liver tumors in macaques with several nitrosamines and aflatoxin B1 and these tumors produce alpha-fetoprotein (AFP) which can be assayed for both diagnosis and therapy. Thus far, therapy of hepatocellular carcinoma has been most successful with surgical resection; and the tumor mass and serum AFP have been less responsive to single agent chemotherapy. These nonhuman primate models are useful for an understanding of the cause, diagnosis, prevention, and treatment of the human disease.

Animals

Diagnosis of pregnancy in chimpanzees using the nonhuman primate pregnancy test kit.

The usefulness of The Nonhuman Primate Pregnancy Test kit for diagnosis of pregnancy in chimpanzees was determined. This hemagglutination inhibition test for urinary chorionic gonadotropin accurately indicated conception by positive responses in 151 to 153 specimens collected between 20 and 133 days after the estimated day of fertilization. The rate of false positive responses did not exceed 1%.

Animals