Spontaneous neoplasia in the baboon (Papio spp.)

BACKGROUND: There are several comprehensive reviews of spontaneous neoplasia in non-human primates that compile individual cases or small numbers of cases, but do not provide statistical analysis of tumor incidence, demographics, or epidemiology. METHODS: This paper reports all spontaneous neoplasms (n = 363) diagnosed over a 15-year period in a baboon colony with an average annual colony population of 4000. RESULTS: A total of 363 spontaneous neoplasms were diagnosed in 313 baboons: 77 cases were males (25%) and 236 were females (75%); ages ranged from 1 month to 33 years (mean 16.5, median 17). CONCLUSIONS: The organ systems affected in descending order of number of neoplasms were hematopoietic organs (n = 101, 28%), urogenital tract (n = 78, 21%), integument (n = 43, 12%), alimentary tract (n = 43, 12%), endocrine organs (n = 40, 11%), nervous system (n = 33, 9%), musculoskeletal system (n = 5, 1%), and respiratory system (n = 4, 1%). Malignant cases numbered 171 (47%); 192 (53%) cases were benign.     

Spontaneous pathology of the common marmoset (Callithrix jacchus) and tamarins (Saguinus oedipus, Saguinus mystax)

Background  Marmosets and tamarins are increasingly used in research, but their pathology remains poorly defined compared with Old World primates.

Methods  Necropsy records of 129 marmosets and 52 tamarins were reviewed; none was used experimentally.

Results  The most common marmoset lesions were dehydration, emaciation, nephritis, colitis, and inanition. The most common tamarin lesions were dehydration, ascites, emaciation, and congestive heart failure. Colitis and heart disease were the most common cause of death in marmosets and tamarins, respectively. Immature marmoset and tamarin deaths often occurred within the first month of life. Immature marmosets usually died from inanition, stillbirth, and colitis; immature tamarins from atelectasis, stillbirth, heart failure, and colitis. Lymphoma was the most common neoplasm for both marmosets and tamarins.

Conclusion  The findings were similar to prior reports with differences in frequency and severity. We report the first case of endometriosis in a marmoset.     

Spontaneous disc degeneration in the baboon model: magnetic resonance imaging and histopathologic correlation

Degenerative disc disease is a major source of disability in humans. The baboon model is an excellent natural disease model to study comparable human disease, because baboons are relatively large (adult males 20-26 kg, adult females 12-17 kg), long-lived (30-45 years), well defined, easy to use, and closely related to humans. Published investigations with plain radiographs of disc degeneration in baboons indicated vertebral anatomy and changes that were remarkably similar to those seen in humans, and it would be valuable to determine if magnetic resonance imaging (MRI) and histopathologic evaluation would be useful methods for studying the model, as MRI allows multi-planar visualization of tissues without the use of intravenous contrast and it is superior for evaluating disc hydration, annulus tears, and herniations. The thoracolumbar junctions from 47 randomly selected baboons, ranging in age from 2 weeks to 34 years, were evaluated with MRI and histopathology. Excellent correlation with MRI was observed for changes in disc desiccation, height, and age (P < 0.001). The pathologic analysis demonstrated P values of < 0.001 when comparing histopathology with age and MRI results. All severely degenerated discs seen by MRI were in baboons 14 years of age or older.     

Spontaneous gallbladder pathology in baboons

Background Gallbladder pathology (GBP) is a relatively uncommon, naturally occurring morbidity in both baboons and humans. Methods A retrospective analysis was performed on 7776 necropsy reports over a 20 year period to determine the prevalence of baboon GBP. Results Ninety‐seven cases of GBP were identified, yielding a 20 year population prevalence of 1.25%. GBP is more common in adult female baboons, occurring with a female to male ratio of nearly 2:1. Among gallbladder pathologies, cholecystitis (35.1%) and cholelithiasis (29.9%) were the most prevalent abnormalities, followed by hyperplasia (16.5%), edema (15.5%), amyloidosis (5.2%), fibrosis (4.1%), necrosis (4.1%), and hemorrhage (1.0%). Conclusion Many epidemiologic similarities exist between GBP in baboons and humans suggesting that the baboon may serve as a reliable animal model system for investigating GBP in humans.     

Gastrointestinal stromal tumors in a baboon, a spider monkey, and a chimpanzee and a review of the literature

Background  Gastrointestinal stromal tumors (GISTs) are believed to originate from the intestinal pacemaker cells (interstitial cells of Cajal) or their progenitor cells. Spontaneous tumors have been reported in dogs, horses, rhesus, and a chimpanzee and they have been produced experimentally in mice and rats. GISTs represent a diagnostic challenge because they cannot be differentiated from non-lymphoid mesenchymal tumors without using human c-kit (CD117) immunohistochemistry.
Methods  Three neoplasms were incidental findings at necropsy in the stomachs of a baboon and a spider monkey and in the rectum of a chimpanzee.
Results  The GISTs were initially diagnosed grossly and histologically with hematoxylin and eosin as leiomyomas. Immunohistochemical analysis revealed that all three were c-kit (CD117) positive.
Conclusions  These are the first reports of GISTs in the baboon and spider monkey and the second in a chimpanzee. The occurrence of GISTs in non-human primates may provide a unique opportunity to study these tumors.     

LRP5 sequence and polymorphisms in the baboon

Background  LRP5 is known to have an important relationship with bone density and a variety of other biological processes. Mapping to human chromosome 11q13.2, LRP5 shows considerable evolutionary conservation. Orthologs of this gene exist in many species, although comparison of human LRP5 with other non-human primates has not been performed until now.
Methods  We reported the complementary DNA (cDNA) sequence and deduced amino acid sequence for baboon LRP5 , and compared the baboon and human sequences. cDNA sequences for 21 baboons were examined to identify single-nucleotide polymorphisms (SNPs).
Results  Sequences of coding regions in human and baboon LRP5 showed 97– 99% homology. Twenty-five SNPs were identified in the coding region of baboon LRP5 .
Conclusion  The observed degree of coding sequence homology in LRP5 led us to expect that the baboon may serve as a useful model for future research into the role(s) of this gene in primate metabolic diseases.     

Primary hepatic neuroendocrine carcinoma in a baboon (Papio sp.)

Background  Primary neuroendocrine carcinomas of the liver have rarely been reported in humans and domestic animals, but not in non-human primates.
Methods  We describe the morphologic and immunohistochemical features of a primary hepatic neuroendocrine carcinoma found in a 29-year-old female baboon.
Results and conclusions  The neoplasm was characterized by multiple solid nodules that were multifocally distributed in the liver. Metastases were not observed. Histologically, the neoplasm was composed of cords and nests of epithelial cells arranged in a neuroendocrine pattern, occasionally forming glandular and rosette-like structures. On immunohistochemical evaluation, the neoplastic cells were immunopositive for pancytokeratin, chromogranin A, neuron-specific endolase, and synaptophysin and were negative for vimentin, S100 protein, glucagon, and insulin.     

Immunocytochemical localisation of GABA in endocrine cells of the rat entero-pancreatic system

The occurence of GABA-containing cells in the rat entero-pancreatic system was investigated by using anti-GABA-glutaraldehyde antibodies at the light and electron microscope level. In the pancreas, the B cells showed intense immunoreactivity, contrary to non-B and exocrine cells. Moreover, post-embedding immunogold staining was localised mostly in mitochondria, close to rough endoplasmic reticulum and in the nucleus. The insulin granules appeared non-significantly stained, which suggests the lack of cosecretion of GABA together with insulin. In the duodenum, GABA immunoreactivity was detected in certain endocrine cell types, suggesting a possible interaction with this amino acid. The well established GABAergic innervation in the enteric system was also confirmed by immunolabelling.     

Pathology of the male baboon (Papio spp.) urogenital system

Background Comprehensive reports on male baboon urogenital pathology are not available. Methods We performed a retrospective study of 2246 male baboon necropsy records over 19 years. Results A total of 289 urogenital lesions were diagnosed in 197 (8.8%) baboons. The most frequently affected organs in decreasing order were kidney, testicle, urinary bladder, penis and prepuce, seminal vesicle, ureter, and prostate. Lesions were rare in the urethra, scrotum, and epididymis. The most common diagnoses in decreasing order were nephritis, urinary bladder cystitis, nephrocalcinosis, pyelonephritis, renal cysts, renal amyloidosis, testicular atrophy, penile/preputial dermatitis, hydronephrosis, orchitis/testicular abscess, glomerulonephritis, renal hemorrhage, hypospadia, nephrosis, renal infarct, hypospermia/aspermia, seminal vesicle mineralization, and hydroureter. We also report six cases of hypospadia, the first report in the baboon. Conclusions The male baboon has a low incidence of urogenital disease and renal disease is the most common malady. The role of herpesvirus papio 2 needs further study.     

Aspiration cytodiagnosis of pancreatic endocrine tumours

We have reviewed fine needle aspirates from 11 patients with pancreatic endocrine tumours and evaluated the diagnostic criteria as well as those proposed in the literature in an attempt to formulate reliable criteria for the cytological diagnosis of these tumours. As expected, no single criterion was reliable for diagnosis: however, cells with rounded or polygonal rather than a columnar shape, cytoplasmic granularity, and eccentricity of round or oval nuclei with a finely stippled, evenly distributed chromatin pattern were features which taken together, usually enabled one to make a reliable diagnosis. A striking feature of the smears was the cellular monotony and absence of pleomorphism of the tumour cells. Immunocytochemistry and electron microscopy identified tumour products and confirmed the diagnosis.     

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 ).
Methods  We reviewed clinical records and necropsy reports of 87 adult chimpanzees for possible causes of heart disease/IC. We examined age, sex, cause of death, weight, diet, environment, infectious diseases, experimental uses and clinical pathology.
Results  The overall prevalence of heart disease in chimpanzees was 67.81%; the prevalence of IC was 51.72%. The prevalence of IC was significantly higher in males (60.32%) than that in females (29.17%, P  = 0.009). The prevalence of other heart disease was higher in females (25%) than that in males (12.70%, P  = 0.165). Heart failure occurred in 47.13% of chimpanzees. Heart disease was the primary cause of death in 34.49% of chimpanzees; 29.88% died of unknown causes.
Conclusions  We found no evidence that diet, environment, viral agents, experimental use or disease exposure contributed to the deaths resulting from IC in chimpanzees.     

Neoplasia in the chimpanzee (Pan spp.)

Background  Chimpanzees have over 98% genomic sequence homology with humans and may have a similar host response to malignancy. There is minimal information concerning cancer in the chimpanzee and such information would be valuable to individuals caring for and using them for research.
Methods  Spontaneous neoplasia that was documented in two chimpanzee colonies and in the literature were evaluated statistically.
Results  In all, 105 spontaneous and 12 experimental neoplasms were diagnosed. Seventy-four spontaneous tumors occurred in females, 24 in males, and seven in animals of undetermined sex. Of the spontaneous tumors 89 were benign, 14 were malignant, and two were undetermined. Neoplasia was most common in the urogenital system in females.
Conclusions  Neoplasia is not uncommon in the chimpanzee, is generally benign, and occurs primarily in the urogenital system in females.     

Spontaneous pancreatic islet amyloidosis in 40 baboons

Spontaneous amyloidosis occurs in many nonhuman primate species but remains difficult to diagnose and treat. Nonhuman primates continue to offer promise as animal models in which to study amyloidosis in humans. Amyloidosis was not diagnosed clinically but was found histologically in four male and 36 female baboons. The baboons averaged 18 years of age at death (range, 7-28 years). Clinical signs, if present, were hyperglycemia and cachexia. Blood glucose values were elevated in 12 of 30 baboons with available clinical pathology data. Four baboons had been clinically diagnosed as diabetic and three were treated with insulin. Amyloid was found in the islets of Langerhans of the pancreas in 40 baboons; 35 baboons had amyloid only in the islets of Langerhans. Amyloid was found in nonislet tissue of baboons as follows: five, nonislet pancreas; four, intestine and adrenal; three, kidney; two, prostate and spleen; and one each, lymph node, liver, gall bladder, stomach, tongue, urinary bladder, and salivary gland. Sections of paraffin-embedded tissues were evaluated for amyloid with hematoxylin and eosin (HE) and congo red (CR) staining, and using immunohistochemistry for human islet amyloid polypeptide (IAPP), calcitonin gene-related peptide (CGRP), glucagon, pancreatic polypeptide (PP), somatostatin (SS), and porcine insulin. Islet amyloid was positive with HE in 40 baboons, with CR in 39 baboons, and with IAPP and CGRP in 35 baboons. IAPP and CGRP only stained islet amyloid. PP, SS, glucagon, and porcine insulin did not stain amyloid. Islet amyloidosis in the baboon appears to be difficult to diagnose clinically, age-related, and similar to islet amyloidosis in other species. The baboon may be a good model for the study of islet amyloidosis in humans.     

Decreased blood vessel density and endothelial cell subset dynamics during ageing of the endocrine system

Age‐associated alterations of the hormone‐secreting endocrine system cause organ dysfunction and disease states. However, the cell biology of endocrine tissue ageing remains poorly understood. Here, we perform comparative 3D imaging to understand age‐related perturbations of the endothelial cell (EC) compartment in endocrine glands. Datasets of a wide range of markers highlight a decline in capillary and artery numbers, but not of perivascular cells in pancreas, testis and thyroid gland, with age in mice and humans. Further, angiogenesis and β‐cell expansion in the pancreas are coupled by a distinct age‐dependent subset of ECs. While this EC subpopulation supports pancreatic β cells, it declines during ageing concomitant with increased expression of the gap junction protein Gja1. EC‐specific ablation of Gja1 restores β‐cell expansion in the aged pancreas. These results provide a proof of concept for understanding age‐related vascular changes and imply that therapeutic targeting of blood vessels may restore aged endocrine tissue function. This comprehensive data atlas offers over > 1,000 multicolour volumes for exploration and research in endocrinology, ageing, matrix and vascular biology.     

Genetics and the evolution of primate enamel thickness: a baboon model

The thickness of mammalian tooth enamel plays a prominent role in paleontology because it correlates with diet, and thicker enamel protects against tooth breakage and wear. Hominid evolutionary studies have stressed the importance of this character for over 30 years, from the identification of "Ramapithecus" as an early Miocene hominid, to the recent discovery that the earliest hominids display molar enamel intermediate in thickness between extant chimpanzees and Australopithecus. Enamel thickness remains largely unexplored for nonhominoid primate fossils, though there is significant variation across modern species. Despite the importance of enamel thickness variation to primate evolution, the mechanisms underlying variation in this trait have not yet been elucidated. We report here on the first quantitative genetic analysis of primate enamel thickness, an analysis based on 506 pedigreed baboons from a captive breeding colony. Computed tomography analysis of 44 Papio mandibular molars shows a zone of sufficiently uniform enamel thickness on the lateral surface of the protoconid. With this knowledge, we developed a caliper metric measurement protocol for use on baboon molars worn to within this zone, enabling the collection of a data set large enough for genetic analyses. Quantitative genetic analyses show that a significant portion of the phenotypic variance in enamel thickness is due to the additive effects of genes and is independent of sex and tooth size. Our models predict that enamel thickness could rapidly track dietary adaptive shifts through geological time, thus increasing the potential for homoplasy in this character. These results have implications for analyses of hominoid enamel thickness variation, and provide a foundation from which to explore the evolution of this phenotype in the papionin fossil record.     

Eosinophilic bronchitis-like lesion as the cause of death in a Macaca mulatta: a first case report

BACKGROUND: Eosinophilic bronchitis is a recently described, relatively benign condition in humans that is characterized by a corticosteroid-responsive chronic cough and sputum eosinophilia without the abnormalities of airway function seen in asthma. The exact cause of this condition is currently unknown, however has been associated with various occupational exposures in humans. It has also been reported to progress to irreversible airway obstruction. This disease has been reported in dogs and horses, but not in non-human primates. METHODS: Gross examination of an otherwise healthy 13-year-old, colony-born Macaca mulatta, which died of severe non-responsive respiratory distress revealed that the lungs were markedly inflated and moist. RESULTS: Hematoxylin and eosin-stained sections from the lungs contained widespread accumulation of eosinophils, sloughed epithelial cells, and mucus centered around bronchioles and adjacent airways. There was no evidence of mast cell infiltration of peribronchiolar smooth muscle, goblet cell hyperplasia, or basement membrane thickening. CONCLUSIONS: This ruled out recurrent episodes as would be expected in asthma, favoring the diagnosis of an eosinophilic bronchitis-like lesion. We report a first case of eosinophilic bronchitis-like features in a M. mulatta.     

Trichobezoars in baboons

Background  There is little information available concerning trichobezoars in the non-human primate literature.
Methods  We evaluated 118 cases of trichobezoar in baboons over a 29-year period at the Southwest National Primate Research Center.
Results  The anatomic locations affected in decreasing order were the stomach, small intestine, cecum, esophagus and colon. The most common clinical history was weight loss. The most frequent associated pathology included gastrointestinal inflammation and ulceration, emaciation, peritonitis, intussusception, pneumonia, and aspiration. Trichobezoars were the cause of death in nine baboons and the reason for euthanasia in 12. Females were 2.14 times more likely than males to be affected. The greater the percentage of group housing time, the more likely the baboon is to develop trichobezoars.
Conclusions  The baboon may present a useful model to evaluate the etiology, genetic predisposition, physiopathology, neurobiology, and treatment response of trichobezoars.     

Evaluation of trophoblast invasion in placental bed biopsies of the baboon,with immunohistochemical localisation of cytokeratin,fibronectin, and laminin

Abstract: Biopsies of placentas (n = 21), placental bed (n = 17) and decidua (n = 26) of various gestation periods (30 to 140 days) were used to study trophoblast invasion in the baboon. Application of immunohistochemical staining for cytokeratin allowed proper identification of trophoblast. Earlier reports showing restricted trophoblast invasion in this species were confirmed by the finding that endovascular trophoblast was present in only one third of biopsies containing spiral arteries. Moreover, immunostaining for cytokeratin revealed that in several arteries only a few isolated trophoblastic cells were present, while the vessel had not undergone the normal physiological change. Trophoblast invasion could only be detected within decidual, but not in myometrial, segments of spiral arteries. Interstitial trophoblast invasion was very limited and multinuclear giant cells were absent. Immunohistochemical staining suggested a contribution of laminin to the fibrinoid deposition within the physiologically changed spiral arteries, while fibronectin was present intracellularly in the invaded trophoblast. Because of differences in the trophoblast invasion pattern, the baboon cannot be regarded as a satisfactory experimental model to explore results of inadequate endovascular trophoblast invasion which, in the human, leads to pregnancy complications such a preeclampsia.     

The endocrine cells in the gastroenteropancreatic system of the bowfin, Amia calva L.: an immunohistochemical, ultrastructural, and immunocytochemical analysis.

The gastroenteropancreatic (GEP) endocrine system of bowfin (Amia calva) was described using light and electron microscopy and immunological methods. The islet organ (endocrine pancreas) consists of diffusely scattered, mostly small islets and isolated patches of cells among and within the exocrine acini. The islets are composed of abundant, centrally located B cells immunoreactive to bovine and lamprey insulin antisera and D cells showing a widespread distribution and specificity to somatostatin antibodies. A and F cells are present at the very periphery of the islets and are immunoreactive with antisera against glucagon (and glucagon-like peptide) and several peptides of the pancreatic polypeptide (PP)-family, respectively. The peptides of the two families usually collocates within the same peripheral islet cells and are the most common immunoreactive peptides present in the extra-islet tissue. Immunocytochemistry and fine structural observations characterised the granule morphology for B and D cells and identified two cell types with granules immunoreactive to glucagon antisera. These two putative A cells had similar granules, which were distinct from either B or D cells, but one of the cells had rod-shaped cytoplasmic inclusions within cisternae of what appeared to be rough endoplasmic reticulum. The inclusions were not immunoreactive to either insulin or glucagon antisera. Only small numbers of cells in the stomach and intestine immunoreacted to antisera against somatostatin, glucagon, and PP-family peptides. The paucity of these cells was reflected in the low concentrations of these peptides in intestinal extracts. The GEP system of bowfin is not unlike that of other actinopterygian fishes, but there are some marked differences that may reflect the antiquity of this system and/or may be a consequence of the ontogeny of this system in this species.     

Record review of baboons with histologically confirmed endometriosis in a large established colony

Spontaneous endometriosis was diagnosed in 43 baboons over a 14-year period. Thirty-seven have died; five remain alive; one was sold and lost to follow-up. The average age at diagnosis was 17.2 years; 29 (67%) were between 12 and 21 years of age. Fifteen (35%) were diagnosed by biopsy and received surgical excision of the endometriotic tissue; four of these were identified during caesarian section, confirming one prior report of endometriosis in pregnant animals. Twenty-eight (65%) were diagnosed at or shortly preceding necropsy. When diagnosed by a palpable abdominal mass, there was a significantly greater likelihood the animal died or was killed as a result of complications of endometriosis. When diagnosis was at necropsy, there was a significantly greater likelihood that the animal died from causes unrelated to endometriosis. Early identification with surgical removal appears to provide a benefit for both survival and delivering offspring after diagnosis. In twenty-one baboons (49%), endometriosis affected multiple sites within the peritoneal cavity. In the remaining baboons, lesions were more localized. Ovarian involvement was seen in sixteen (37%) of these baboons. This paper is the first to describe significant ovarian involvement in baboons, previously considered a limitation of the usefulness of this species as an animal model. We also describe the first reported endometriosis seeding of an abdominal surgery scar in a baboon. Many of these baboons were middle aged, had few or no offspring, or had evidence of a long duration of uninterrupted menstrual cycles, consistent with risk factors for women. Endometriosis was an incidental finding in 17 (40%) of these baboons, consistent with previous reports of minimal endometriosis as a common asymptomatic finding in baboons and in women. Overall, endometriosis in baboons presents a spontaneously occurring animal model that shares important features with the disease in women and the rhesus macaque.