MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques.

Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques (Macaca mulatta) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoroacetate ([18F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [18F]fluorothymidine ([18F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1-rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans.

Transthoracic echocardiography and cardiac biomarkers in healthy captive male and female squirrel monkeys (Saimiri spp.).

BACKGROUND: Echocardiography is the most frequently used non -invasive diagnostic tool to evaluate cardiac anatomy and function in domestic species but increasingly also in non -domestic species, especially since cardiac disease is being recognized as an important cause of death in captive primates. The purpose of this cross -sectional study was to investigate the feasibility of transthoracic echocardiography in healthy squirrel monkeys as well as to provide species specific normal values for standard echocardiographic measurements. A secondary aim was to determine plasma and serum levels of the cardiac biomarkers, N -terminal pro -brain natriuretic peptide (NT -proBNP) and cardiac troponin T (cTnT). Furthermore, a commercial, non -invasive, smartphone -based ECG (AliveCor Vet TM) monitoring device was used to evaluate the heart rate and rhythm and to diagnose possible arrhythmias. RESULTS: In this study, transthoracic echocardiography of 14 squirrel monkeys was performed in right and left lateral recumbency. Similar standard right parasternal and left apical images were obtained as in dogs and cats and normal values for routine two -dimensional, time motion mode and Doppler mode measurements were generated. Thirteen animals were considered healthy and one squirrel monkey was identified with significant aortic dilation and regurgitation and consequently values obtained from this animal were not used when species specific normal values were calculated. NT -ProBNP and cTnT concentrations were available for 7 of the 13 healthy monkeys with NT -proBNP concentrations below detection limit in all animals and a mean cTnT concentration of 0.049 ng/mL. Electrocardiography was performed in all squirrel monkeys. The mean heart rate was 172 bpm. Frequent supraventricular premature beats were diagnosed in the squirrel monkey suffering from significant aortic dilation and regurgitation. CONCLUSION: This study presents echocardiographic normal values and additional cardiovascular data in anaesthetised Saimiri monkeys, fundamental from both the perspective of zoo animal health care as well as scientific research, since the squirrel monkey is often used as an animal model for human disease.

Solitary Osteochondroma in a Ring-Tailed Lemur (Lemur catta).

A 20-y-old, male, ring-tailed lemur (Lemur catta) presented with a large, firm mass on the proximal caudolateral left femur. The animal displayed no clinical signs associated with the mass. Radiographs revealed a mineralized mass protruding from the femur, with an intact femoral cortex. Histopathology diagnosed osteochondroma in view of the presence of a peripheral layer of cartilage with progressive endochondral ossification and typical remodeling of bony trabeculae. The mass grew quickly after the initial biopsy, and a second surgery to debulk 95% of the tumor was performed. Histopathologic features of the larger samples were similar to those of the initial biopsies, with the cartilage layer being discontinuous and development of bone from some borders progressing directly from a periost-like layer. Nineteen months after the second surgery, the mass had regrown and extended further proximally on the femur toward the epiphysis, but the animal remained asymptomatic, and additional debulking was not attempted. This report is the first description of an osteochondroma in a prosimian and describes unique behavior of the tumor compared with osteochondromas found in humans, dogs, and cats.

Spinal degenerative disk disease (DDD) in female macaque monkeys: epidemiology and comparison with women.

Spinal degenerative disk disease (DDD) in a radiographic, cross-sectional sample of 192 female macaque monkeys, approximately 5-30 years old, is described. The presence and extent of disk space narrowing (DSN) and anterior osteophytosis were assessed with reference to age, average lifetime body mass. and distribution within the thoracolumbar spine. Age was a strong correlate of disk narrowing and osteophytosis, with early signs appearing at equivalent ages in both species and increasing in prevalence thereafter. Macaques showed a far greater prevalence of DDD, especially in the oldest age group, than has been reported in the human data. Body mass was associated with disk narrowing in the macaque, but not with osteophytosis. The two species differed little in the pattern of distribution of DDD along the spine. Our results suggest that bipedality is not the singular, or even the most important, biomechanical factor in the development of human DDD. Rather, others shared postural regimes, e.g., sitting, may be responsible for the onset and progression of DDD in both species. The macaque model could substantially add to the understanding and, potentially, treatment of this oftentimes debilitating condition.

Cecal volvulus in two African green monkeys (Cercopithecus athiops sabeus).

Following short-term signs of weakness, depression, and/or anorexia of less than 24 h, two adult male African green monkeys (Cercopithecus aethiops sabeus) of St. Kitts origin died from complications of cecal volvulus. Gaseous distention was radiologically apparent in one animal. Necropsy of both monkeys revealed cecal volvulus, one at the ileocecal junction and one involving a segment of the distal portion of the ileum and cecum. Congestion and hemorrhage were evident microscopically in the lamina propria of the affected intestine, with variable necrosis.