Browsing by Author "Rogers, Jeffrey"

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    Analysis of Prostate-Specific Antigen Transcripts in Chimpanzees, Cynomolgus Monkeys, Baboons, and African Green Monkeys
    (PLoS One, 2014) Mubiru, James N.; Yang, Alice S.; Olsen, Christian; Nayak, Sudhir; Livi, Carolina B.; Dick Jr., Edward J.; Owston, Michael; Garcia-Forey, Magdalena; Shade, Robert E.; Rogers, Jeffrey
    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).
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    Nonhuman Primates as Models for Studies of Prostate Specific Antigen and Prostatic Diseases
    (The Prostate, 2008) Mubiru, James N.; Hubbard, Gene B.; Dick, Edward J.; Furman, Jaime; Troyer, Dean A.; Rogers, Jeffrey
    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, PSAhas 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. METHODS. Weevaluated cynomolgus macaques, rhesus macaques, baboons, and marmosets for their suitability as models for the study of PSA biology and prostatic diseases. RESULTS. Prostates of several nonhuman primates are anatomically similar to the human counterpart. Anti-human PSA antibody detected PSA antigens in all the Old World monkeys (cynomolgus macaques, rhesus macaques, and baboons) but not in marmosets. Of the Old World monkeys, cynomolgus macaques have the highest serum PSA levels; baboons have the lowest. Serum PSA levels from macaques includes a number of outlier samples with unusually high values. We also report two cases of abnormal pathologies in macaques accompanied by high serum PSA levels. One case consisted of prostatic hyperplasia involving both glandular and basal cells in a cynomolgus macaque and another of glandular hyperplasia and atrophy in a rhesus macaque. The finding that pathological changes in the prostate of macaques may lead to increases in serum PSA is worthy of further exploration. CONCLUSION. Cynomolgus macaques and rhesus macaques are promising animal models for PSA biology studies.
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    A preliminary report on the feeding of cynomolgus monkeys (Macaca fascicularis) with a high-sugar high-fat diet for 33 weeks
    (Journal of medical primatology, 2011) Mubiru, James N.; Garcia-Forey, Magdalena; Higgins, Paul B.; Hemmat, Peggah; Cavazos, Nicole E.; Owston, Michael A.; Bauer, Cassondra A.; Shade, Robert E.; Comuzzie, Anthony G.; Rogers, Jeffrey
    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. Methods We fed 15 cynomolgus monkeys ad libitum a high-sugar high-fat (HSHF) diet for 33 weeks. Body weight, body composition, serum lipids, and insulin were measured at baseline and at 33 weeks. Results The animals tolerated the HSHF diet very well. In the intervention group, total serum cholesterol and low-density lipoprotein cholesterol were 3- and 5-fold higher, respectively, at 33 weeks as compared with their baseline levels. Serum high-density lipoprotein cholesterol and triglycerides were not significantly affected. Dual-energy X-ray absorptiometry (DXA) analysis of the intervention group indicated that the trunk fat mass increased by 187% during this period. Conclusions Cynomolgus monkeys should be a useful model for investigating the interactions of diet and other factors such as genetics in the development of the metabolic syndrome.
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    A Preliminary Study of the Baboon Prostate Pathophysiology
    (The Prostate, 2007) Mubiru, James N.; Hubbard, Gene B.; Dick Jr., Edward J.; Butler, Stephanie D.; Valente, Anthony J.; Troyer, Dean A.; Rogers, Jeffrey
    Prostate cancer, benign prostatic hyperplasia, and prostatitis frequently affect men worldwide. At present there are no suitable animal models for these diseases. This study explores the potential use of the baboon as a model for prostatic diseases. METHODS. Prostates of 48 baboons of different ages were studied. Prostate specific antigen (PSA) and alpha-methyl-acyl-CoA racemase (AMACR) were localized in the different lobes of the prostate by Western blotting and immunohistochemistry. PSA in baboon serum was demonstrated by radioimmunoassay and western blotting. BaboonAMACRcDNA was cloned and its expression assayed in baboon tissues. RESULTS. The baboon prostate is anatomically and histologically similar to its human counterpart, with cranial and caudal lobes corresponding to central and peripheral zones of the human prostate. We found lymphocytic infiltration (91%), and sclerosing/atrophic lesions (34%). PSA tissue immunostaining intensity and alpha-methyl-acyl-CoA racemase (AMACR) gene expression levels differed between the cranial and caudal lobes of the prostate. The cloned baboon AMACR cDNA showed 96% homology with its human counterpart. Anti-human AMACR, PSA and basal keratin antibodies stained intracellular and basement membrane structures in the baboon prostate. The sclerosing/atrophic lesions were comparable to their human counterparts. CONCLUSIONS. The similarity of baboon prostate to its human counterpart and the fact that human antibodies (AMACR, PSA, basal keratin) are reactive to baboon prostatic proteins indicates that the baboon is a promising model for human prostatic diseases.
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    Serum Prostate Specific Antigen Changes in Cynomolgus Monkeys (Macaca fascicularis) on a High Sugar High Fat Diet
    (The Prostate, 2012) Mubiru, James N.; Garcia-Forey, Magdalena; Cavazos, Nicole; Hemmat, Peggah; Dick, Edward J.; Owston, Michael A.; Bauer, Cassondra A.; Shade, Robert E.; Rogers, Jeffrey
    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. METHODS. Serum PSA in a colony of cynomolgus monkeys was assayed and correlated to body weight, prostate weight, and age. In addition, 15 animals were selected and fed a high sugar high fat (HSHF) diet for 49 weeks to increase their BMI and correlate it to PSA RESULTS. Serum PSA levels were positively correlated to prostate weight (r ¼ 0.515, P ¼ 0.025) and age (r ¼ 0.548, P ¼ 0.00072) but was not significantly correlated to body weight (r ¼ 0.032, P ¼ 0.419). For the animals on the HSHF diet, body weight, lean mass, fat mass, and BMI were significantly higher at 49 weeks than at baseline (P < 0.01). PSA was not significantly correlated to body weight and insulin at both baseline and 49 weeks. PSA was negatively correlated to BMI and insulin resistance (HOMA-IR) at 49 weeks but not at baseline. In addition, we observed hepatic steatosis and increases in serum liver enzymes. CONCLUSIONS. Increases in BMI in cynomolgus monkeys as a result of consuming a HSHF diet resulted in PSA changes similar to those in humans with increased BMI. Cynomolgus monkeys are a useful model for investigating the relationship between obesity, diabetes, and PSA changes resulting from prostate gland pathology.