Indication of higher salivary α‐amylase expression in hamadryas baboons and geladas compared to chimpanzees and humans

Background Little is known about salivary α‐amylase expression in primates. Methods We compared saliva of gelada and hamadryas baboons, chimpanzees and humans using SDS‐PAGE and immunoblotting. Results and conclusions Amylase expression was increased in hamadryas baboons (P = 0.0376) compared to humans and might indicate dietary starch use in Cercopithecines.     

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.     

A review of spontaneous neoplasia in baboons (Papio spp.)

The baboon has become an increasingly important animal model and accurate information on baboon neoplasia is frequently required for biomedical research. To satisfy this demand, a complete literature search was carried out. Two hundred and four spontaneous neoplasms were found in published literature: 53 cases were male (26%), 76 were female (37%); sex was not reported in 75 cases (37%). Ages ranged from 3 months to 31 years (mean 14.1 years) in the 93 cases that reported them. Spontaneous neoplasms have been documented in Papio cynocephalus and Papio hamadryas as well as in most subspecies and hybrid combinations. The organ systems affected in descending order of number of neoplasms were hematopoietic (n = 53, 26%), alimentary (n = 52, 25%), urogenital (n = 35, 17%), integumentary (n = 26, 13%), endocrine (n = 14, 7%), nervous (n = 12, 5%), musculoskeletal (n = 4, 2%) and respiratory (n = 3, 1%). There were five miscellaneous neoplasms (2%) that could not be classified by system. Lymphosarcoma was the most common neoplasm (n = 51, 25%), and adenocarcinomas were second (n = 23, 11%), followed by squamous cell carcinomas (n = 10, 5%). Malignant cases numbered 114 (56%); 87 cases were (43%) benign. The malignancy of three cases (1%) was unreported.     

Maternal parity affects neonatal survival rate in a colony of captive bred baboons (Papio hamadryas)

Background Non‐human primates, particularly baboons, are valuable as animal models for reproductive research, because of their similarity to humans. Knowledge of colony‐specific pregnancy and neonatal outcomes is essential for interpretation of such research. Methods A retrospective review of the reproductive records of the Australian National Baboon Colony (ANBC) from 1994 to 2006 was performed. Results The overall live birth rate was over 70% of recognized pregnancies. Pregnancy loss was due to equal proportions of spontaneous abortion and stillbirth, and was not affected by maternal age or parity. Stillbirth rates were increased by the use of animals in novel late pregnancy experimental protocols. Neonatal mortality rates were low overall, but significantly higher in primiparous compared with multiparous mothers (P < 0.05). There were no cases of maternal mortality. Conclusions The success of the ANBC breeding programme is demonstrated by the low rate of pregnancy loss, high neonatal survival rate and lack of maternal mortality.     

Development of a pigtail macaque model of sexually transmitted infection/HIV coinfection using Chlamydia trachomatis, Trichomonas vaginalis, and SHIV(SF162P3)

Background Sexually transmitted infections (STIs) are associated with an increased risk of HIV infection. To model the interaction between STIs and HIV infection, we evaluated the capacity of the pigtail macaque model to sustain triple infection with Trichomonas vaginalis, Chlamydia trachomatis, and SHIV_SF162P3. Methods Seven SHIV_SF162P3‐infected pigtail macaques were inoculated with T. vaginalis only (n = 2), C. trachomatis only (n = 1), both T. vaginalis and C. trachomatis (n = 2), or control media (no STI; n = 2). Infections were confirmed by culture and/or nucleic acid testing. Genital mucosa was visualized by colposcopy. Results Characteristic gynecologic signs were observed for both STIs, but not in control animals. Manifestations were most prominent at days 7–10 post‐infection. STIs persisted between 4 and 6 weeks and were cleared with antibiotics. Conclusions These pilot studies demonstrate the first successful STI‐SHIV triple infection of pigtail macaques, with clinical presentation of genital STI symptoms similar to those observed in humans.     

Congenital anomalies in the baboon (Papio spp.)

Background A comprehensive survey of the prevalence of congenital anomalies in baboons has not been previously reported. We report the congenital anomalies observed over a 26‐year period in a large captive baboon colony. Methods A computer search was performed for all baboon congenital anomalies identified at necropsy and recorded on necropsy submissions. Results We identified 198 congenital anomalies in 166 baboons from 9972 necropsies (1.66% of total necropsies). The nervous, urogenital, musculoskeletal, and cardiovascular systems were most commonly affected. The most common organs affected were the brain, bone, heart, testicle, kidney, penis, aorta, and skeletal muscle. The most frequent congenital anomalies were blindness, seizures, and hydrocephalus. Conclusions The baboon has an overall frequency of congenital anomalies similar to humans and other non‐human primates. Although the most frequently affected systems are similar, congenital anomalies involving the digestive system appear to be less common in the baboon.     

Retrobulbar primitive neuroectodermal tumor in a squirrel monkey (Saimiri sciureus)

Background A 2.8‐year‐old female captive‐bred common squirrel monkey (Saimiri sciureus) showed exophthalmos of the right eye, and the eye was surgically enucleated. A tumor mass was found in the eye. Methods Formalin‐fixed tumor samples were examined histopathologically and immunohistochemically for diagnosis. Results The retrobulbar tumor mass adhered to the sclera and infiltrated the choroid. Histopathologically, tumor cells were pleomorphic, arranged in a sheet pattern, and mimicked primitive neuroectodermal cells. The tumor cells were strongly positive for precursor neuronal cell markers (beta III tubulin, neuron‐specific enolase, vimentin, nestin, doublecortin, oligo2, and S‐100), but negative for mature cell markers (cytokeratin, neurofilament, and glial fibrillary acidic protein) and a retinoblastoma marker (rhodopsin). Conclusions This is the first reported case for the retrobulbar location of primitive neuroectodermal tumor in non‐human primates.     

New approach for graded compression spinal cord injuries in Rhesus macaque: method feasibility and preliminary observations

Background Current models of spinal cord injury (SCI) have been ineffective for translational research. Primate blunt SCI, which more closely resembles human injury, could be a promising model to fill this gap. Methods Graded compression SCI was produced by inflating at T9 an epidural balloon as a function of spinal canal dimensions in a non‐uniform group of monkeys. Results Sham injury and cord compression by canal invasion of 50–75% produced minimal morpho‐functional alterations, if at all. Canal invasion of 90–100% resulted in proportional functional deficits. Unexpectedly, these animals showed spontaneous gradual recovery over a 12‐week period achieving quadruped walking, although with persistent absence of foot grasping reflex. Histopathology revealed predominance of central cord damage that correlated with functional status. Conclusions Our preliminary results suggest that this model could potentially be a useful addition to translational work, but requires further validation by including animals with permanent injuries and expansion of replicates.     

Teeth emergence in wild olive baboons in Kenya and formulation of a dental schedule for aging wild baboon populations

Teeth emergence schedules are presented from analysis of 95 wild olive baboons Papio anubis (age range 2–120 months) and compared to recently published results for wild and captive yellow baboons (P. cynocephalus; Phillips-Conroy and Jolly: American Journal of Primatology 15:17–29, 1988). Age at emergence of M1 (20.5 months males, 19.5 months females), I1 (32.5 and 33.5 months) and I2 (40.0 and 39 months) of olive baboons was earlier than in the wild yellow baboons and similar to captive yellow baboons. However, the later emerging teeth were delayed considerably relative to the captive animals and were similar in age of emergence to those of wild yellow baboons. Considerable variation in age of emergence occurred in the later emerging teeth especially among males. Regression analysis of dental scores with age demonstrated differences between olive baboons and captive yellow baboons but not between olive baboons and wild yellow baboons. Combined data on dental scores for wild yellow, olive, and hamadryas baboons provide schedules of AGE (months) = {SCORE – 11.79} ÷ 0.4405 and AGE (months) = {SCORE – 11.24} ÷ 0.4797 for males and females, respectively, which may be used for aging wild baboons. Full permanent dentition in wild baboons is predicted to occur over 1 year later than in captive animals.     

Complete coding sequence and molecular analysis of hepatitis A virus from a chimpanzee with fulminant hepatitis

Background Hepatitis A virus (HAV) infects both humans and non‐human primates, in experimentally infected chimpanzees is typically milder than in humans. In 1982, Abe and Shikata reported a first case of a chimpanzee with fulminant hepatitis caused by spontaneous HAV infection, and the underlying mechanisms of the disease remain unknown. Methods To characterize denoted CFH‐HAV, we conducted cloning and near full‐length sequence analysis. Results Phylogenetic analyses of VP1‐2A and complete sequence comparison between various genotypes and the sample sequence showed clustering in genotype IB. Based on BLAST analysis, the sequence was most closely related to the wild‐type (HM175/WT) isolate. Amino acid and nucleic acid similarities were 99.8% and 94.41%, respectively. Conclusions The chimpanzee may have been infected with human HAV genotype IB. The substitutions in VP2, VP4, 2B, 2C, and 3D, which may enhance virus proliferation, contributed to disease severity culminating in fulminant hepatic failure.     

Epitope mapping of a chimeric CD137 mAb: a necessary step for assessing the biologic relevance of non‐human primate models

Antibody based manipulation of the CD137 (4‐1BB) co‐signaling pathway is an attractive option for the treatment of cancer and autoimmune disease. We developed a chimeric anti‐human CD137 monoclonal antibody (GG) and characterized its function. As a component of planned preclinical studies, we evaluated the binding of GG to activated peripheral blood mononuclear cells (PBMCs) from cynomolgus macaque and baboon against human. Interestingly, GG only recognized human CD137, while a commercial anti‐CD137 mAb (4B4‐1), recognized activated PBMCs from both human and non‐human primates (NHP). Subsequent analysis revealed that the amino acid sequence of CD137 is largely conserved between primate species (～95% identical), with the extracellular domain differing by only 9–10 amino acids. Based on these data, we generated mutant constructs in the extracellular domain, replacing NHP with human CD137 sequences, and identified 3 amino acids critical for GG binding. These residues are likely part of a conformational epitope, as a peptide spanning this region is unable to block mAb binding. These data demonstrate that subtle sequence variations of defined co‐stimulatory molecules amongst primate species can be employed as a strategy for mapping residues necessary for antibody binding to conformational epitopes. Copyright © 2009 John Wiley & Sons, Ltd.     

Transurethral bladder catheterization of male rhesus macaques: a refinement of approach

Background Successful transurethral bladder catheterization in male non‐human primates can be challenging. An optimized approach for consistent and reproducible catheterization using a refined technique is described. Methods Under sedated and non‐sedated conditions, transurethral bladder catheterization was performed on 25 male rhesus macaques of varying ages and body weights over time. A refined technique ensuring optimal lubrication of the urethral canal prior to catheter insertion was utilized along with various single and multiple lumen catheters. Results All animals were successfully catheterized. Sixty‐five catheterization sessions were conducted with a high overall success rate (100%). The incidence of catheter (10%) and post‐catheterization (2%) complications was low. Conclusions The urinary bladder of male rhesus can be reliably and reproducibly catheterized with minimal complication using this approach. Successful catheterization was facilitated by thorough urethral lubrication and using suitable catheters. In addition, this approach may be performed without sedation on thoroughly conditioned animals.     

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.     

A spontaneously occuring mammary gland ductal carcinoma in situ in a rhesus macaque (Macaca mulatta) and a review of spontaneous mammary gland tumors in rhesus monkeys

A spontaneous mammary gland ductal carcinoma in situ was diagnosed in a 6-8-year-old female rhesus macaque (Macaca mulatta). To our knowledge, this is only the tenth case of spontaneous mammary gland tumors to be reported in rhesus monkeys. Despite the paucity of case reports, several theories exist to explain the occurrence of mammary tumors. The Mason Pfizer monkey virus, a type D retrovirus similar to the virus that causes simian acquired immunodeficiency syndrome, has been implicated as a possible etiologic agent. Because this virus has been isolated from normal primate mammary tissue, it is unlikely to be the sole etiologic agent. Other theories include the tumorogenic effects that androgens, growth hormones, irradiation, and aging have on the mammary gland.     

Hormonal synchronization of the menstrual cycles of pigtail macaques to facilitate biomedical research including modeling HIV susceptibility

Background Menstrual cycle synchronization of female pigtail macaques could prove an invaluable resource in studies of the reproductive tract, associated infections, and other potential research fields. We tested whether use of an oral progesterone and estradiol combination tablet could synchronize menstrual cycles following treatment discontinuation. Methods Daily desogestrel 0.075 mg and ethinyl estradiol 0.01 mg were administered orally to three pigtail macaques at visual onset of perineal sex swelling and were continued until all animals had received it for at least 45 days. The hormones were discontinued, and these three macaques and three controls were observed for menstruation and had blood progesterone and estrogen measured over an additional 2‐month period. Results All treatment animals showed spontaneous menstrual cycle synchronization for 2 months after menstrual cycling resumed. Conclusion Progesterone and estradiol combination therapy can be used in pigtail macaques to induce synchronized cycling that persists in the absence of on‐going hormone treatments.     

Reorganization of inter‐chromosomal interactions in the 2q37‐deletion syndrome

Chromosomes occupy distinct interphase territories in the three‐dimensional nucleus. However, how these chromosome territories are arranged relative to one another is poorly understood. Here, we investigated the inter‐chromosomal interactions between chromosomes 2q, 12, and 17 in human mesenchymal stem cells (MSCs) and MSC‐derived cell types by DNA‐FISH. We compared our findings in normal karyotypes with a three‐generation family harboring a 2q37‐deletion syndrome, featuring a heterozygous partial deletion of histone deacetylase 4 (HDAC4) on chr2q37. In normal karyotypes, we detected stable, recurring arrangements and interactions between the three chromosomal territories with a tissue‐specific interaction bias at certain loci. These inter‐chromosomal interactions were confirmed by Hi‐C. Interestingly, the disease‐related HDAC4 deletion resulted in displaced inter‐chromosomal arrangements and altered interactions between the deletion‐affected chromosome 2 and chromosome 12 and/or 17 in 2q37‐deletion syndrome patients. Our findings provide evidence for a direct link between a structural chromosomal aberration and altered interphase architecture that results in a nuclear configuration, supporting a possible molecular pathogenesis.     

Primary malignant non-Hodgkin's lymphoma of the breast: a study of seven cases and literature review

ABSTRACT: INTRODUCTION: Primary breast lymphoma is an uncommon disease with poor clinical outcome. Breast lymphomas present less than 0.5% of malignant breast neoplasms and 2.2% of extranodal lymphomas. This study investigated the clinicopathological features and optimal treatment of PBL. Case presentations Clinical records of seven Moroccan PBL patients, treated at the National Institute of Oncology, Rabat, Morocco, from 2002 to 2010, were reviewed. Six of the patients were women and one a man, with ages ranging from 32 to 76. Five patients had stage IE and two stage IIE. All of the patients were classified with DLBCL. Of seven patients, one received a mastectomy and three excision of the breast lesion. Axillary dissection was performed in three patients. Two patients received chemotherapy followed by radiotherapy, while four received chemotherapy alone. Complete remission (CR) following primary treatment for all patients with PBL except in two cases was obtained. In one patient, recurrence occurred. CONCLUSIONS: There is no consensus on the question of how to best treat PBL: Mastectomy offers no benefit in the treatment of PBL. The combined therapy approach, with chemotherapy and radiotherapy, is the most successful treatment. PBL is poorly represented in rituximab-containing trials in DLBCL patients; there is not much experience with this agent in breast DLBCL. Because of the high incidence of central nervous system (CNS) involvement in PBL patients, many authors strongly believe that patients with aggressive forms of PBL should receive CNS infiltration prophylaxis.     

Clostridium perfringens type E enteritis in calves: two cases and a brief review of the literature

Toxigenic types of Clostridium perfringens are important causes of enteric disease in domestic animals, although type E is putatively rare, appearing as an uncommon cause of enterotoxemia of lambs, calves, and rabbits. We report here two geographically distinct cases of type E enterotoxemia in calves, and diagnostic findings which suggest that type E may play a significant role in enteritis of neonatal calves. The cases had many similarities, including a history of diarrhea and sudden death, abomasitis, and hemorrhagic enteritis. In both cases, anaerobic cultures of abomasum yielded heavy growth of C. perfringens genotype E. Four percent of > 1000 strains of C. perfringens from cases of enteritis in domestic animals were type E, and all (n=45) were from neonatal calves with hemorrhagic enteritis. Furthermore, type E isolates represented nearly 50% of all isolates submitted from similar clinical cases in calves. Commercial toxoids available in North America have no label claims for efficacy against type E infections. Consideration should be given to type E-associated enteritis when planning for the health care of calves.     

Reactivation of latent tuberculosis in rhesus macaques by coinfection with simian immunodeficiency virus

Background Tuberculosis (TB) and AIDS together present a devastating public health challenge. Over 3 million deaths every year are attributed to these twin epidemics. Annually, ～11 million people are coinfected with HIV and Mycobacterium tuberculosis (Mtb). AIDS is thought to alter the spontaneous rate of latent TB reactivation. Methodology Macaques are excellent models of both TB and AIDS. Therefore, it is conceivable that they can also be used to model coinfection. Using clinical, pathological, and microbiological data, we addressed whether latent TB infection in rhesus macaques can be reactivated by infection with simian immunodeficiency virus (SIV). Results A low‐dose aerosol infection of rhesus macaques with Mtb caused latent, asymptomatic TB infection. Infection of macaques exhibiting latent TB with a rhesus‐specific strain of SIV significantly reactivated TB. Conclusions Rhesus macaques are excellent model of TB/AIDS coinfection and can be used to study the phenomena of TB latency and reactivation.