James N. Mubiru

Spontaneous heart disease in the adult chimpanzee (Pan troglodytes)

Background  A high incidence of heart disease, especially idiopathic cardiomyopathy (IC), is seen in chimpanzees (Pan troglodytes).

Nonhuman Primates as Models for Studies of Prostate Specific Antigen and Prostatic Diseases

Because prostate specific antigen (PSA) is released at increased levels into the blood early in the development of prostate cancer, benign prostatic hyperplasia (BPH) and prostatitis, it is widely used as a marker for these diseases. However, PSA has clinical limitations as a screen for prostatic diseases due to its low sensitivity and specificity. There is a strong need to better understand the biology of PSA and factors affecting its serum levels.

A preliminary report on the feeding of cynomolgus monkeys (Macaca fascicularis) with a high-sugar high-fat diet for 33 weeks

Background  The metabolic syndrome is common in populations exposed to a typical Western diet. There is a lack of an animal model that mimics this condition.

Androgen receptor CAG repeat polymorphism in males of six non-human primate species

Background   Androgen receptor [CAG]n microsatellite has been linked to human diseases.

Reovirus-Associated Meningoencephalomyelitis in Baboons

Baboon orthoreovirus (BRV) is associated with meningoencephalomyelitis (MEM) among captive baboons. Sporadic cases of suspected BRV-induced MEM have been observed at Southwest National Primate Research Center (SNPRC) for the past 20 years but could not be confirmed due to lack of diagnostic assays. An immunohistochemistry (IHC)–based assay using an antibody against BRV fusion-associated small transmembrane protein p15 and a conventional polymerase chain reaction (PCR)–based assay using primers specific for BRV were developed to detect BRV in archived tissues. Sixty-eight cases of suspected BRV-induced MEM from 1989 through 2010 were tested for BRV, alphavirus, and flavivirus by IHC. Fifty-nine of 68 cases (87%) were positive for BRV by immunohistochemistry; 1 tested positive for flavivirus (but was negative for West Nile virus and St Louis encephalitis virus by real-time PCR), and 1 virus isolation (VI) positive control tested negative for BRV. Sixteen cases (9 BRV-negative and 7 BRV-positive cases, by IHC), along with VI-positive and VI-negative controls, were tested by PCR for BRV. Three (of 9) IHC-negative cases tested positive, and 3 (of 7) IHC-positive cases tested negative by PCR for BRV. Both IHC and PCR assays tested 1 VI-positive control as negative (sensitivity: 75%). This study shows that most cases of viral MEM among baboons at SNPRC are associated with BRV infection, and the BRV should be considered a differential diagnosis for nonsuppurative MEM in baboons.

Serum prostate specific antigen changes in cynomolgus monkeys (Macaca fascicularis) on a high sugar high fat diet

An inverse relationship between serum prostate specific antigen (PSA) levels and body mass index (BMI) has been reported in men but not in any animal model.

Analysis of prostate-specific antigen transcripts in chimpanzees, cynomolgus monkeys, baboons, and African green monkeys.

The function of prostate-specific antigen (PSA) is to liquefy the semen coagulum so that the released sperm can fuse with the ovum. Fifteen spliced variants of the PSA gene have been reported in humans, but little is known about alternative splicing in nonhuman primates. Positive selection has been reported in sex- and reproductive-related genes from sea urchins to Drosophila to humans; however, there are few studies of adaptive evolution of the PSA gene. Here, using polymerase chain reaction (PCR) product cloning and sequencing, we study PSA transcript variant heterogeneity in the prostates of chimpanzees (Pan troglodytes), cynomolgus monkeys (Macaca fascicularis), baboons (Papio hamadryas anubis), and African green monkeys (Chlorocebus aethiops). Six PSA variants were identified in the chimpanzee prostate, but only two variants were found in cynomolgus monkeys, baboons, and African green monkeys. In the chimpanzee the full-length transcript is expressed at the same magnitude as the transcripts that retain intron 3. We have found previously unidentified splice variants of the PSA gene, some of which might be linked to disease conditions. Selection on the PSA gene was studied in 11 primate species by computational methods using the sequences reported here for African green monkey, cynomolgus monkey, baboon, and chimpanzee and other sequences available in public databases. A codon-based analysis (dN/dS) of the PSA gene identified potential adaptive evolution at five residue sites (Arg45, Lys70, Gln144, Pro189, and Thr203).

Abstract 970: Effect of feeding a high fat, high simple carbohydrate diet on serum prostate specific antigen (PSA) in cynomolgus monkeys

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Introduction The prostate specific antigen (PSA) test is used for screening and monitoring of prostate cancer. However, PSA has clinical limitations as it is elevated in other pathological conditions other than prostate cancer. PSA is also influenced by other physiological and environmental variables like genetics and diet. The aim of this study was to investigate the effect of feeding a high fat, high simple carbohydrate (HFHSC) diet on serum PSA in a nonhuman primate species. Methods Fifteen cynomolgus monkeys (Macaca fascicularis) were fed an HFHSC diet for 4 months. Body weight and Dual energy X-ray absorptiometry (DEXA) measurements were done at 0, 8 and 16 weeks. Blood was also drawn from these animals and used to assay serum PSA and serum insulin levels. Results View this table: Conclusions Feeding cynomolgus monkeys with an HFHSC diet for 4 months resulted in a significant increase in serum PSA levels. The mechanisms underlying this change in serum PSA is still under investigation, however, chronic hyper-insulinemia as indicated in this study might be one of the contributing factors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 970.