Oral squamous cell carcinoma in a pigtailed macaque (Macaca nemestrina).

An adult, gravid, female pigtailed macaque (Macaca nemestrina) presented for facial swelling centered on the left mandible that was approximately 5 cm wide. Differential diagnoses included infectious, inflammatory, and neoplastic origins. Definitive antemortem diagnosis was not possible, and the macaque's condition worsened despite supportive care. Necropsy findings included a mandibular mass that was locally invasive and expansile, encompassing approximately 80% of the left mandibular bone. The mass replaced portions of the soft palate, hard palate, sinuses, ear canal, and the caudal-rostral calvarium and masseter muscle. Histologically, the mass was a neoplasm that was poorly circumscribed, unencapsulated, and infiltrative invading regional bone and soft tissue. The mass consisted of polygonal squamous epithelial cells with intercellular bridging that breached the epithelial basement membrane and formed invasive nests, cords, and trabeculae. The mitotic rate averaged 3 per 400× field of view, with occasional bizarre mitotic figures. Epithelial cells often exhibited dyskeratosis, and the nests often contained compact lamellated keratin (keratin pearls). The neoplasm was positive via immunohistochemistry for pancytokeratin, variably positive for S100, and negative for vimentin, smooth muscle actin, and desmin. The gross, histologic, and immunohistochemical findings were consistent with an aggressive oral squamous cell carcinoma. The neoplasm was negative via PCR for papilloma virus. In general, neoplasia in macaques is rare. Although squamous cell carcinomas are one of the most common oral neoplasia in many species, to our knowledge this case represents the first reported oral squamous cell carcinoma in a pigtailed macaque.

Risk factors for dystocia in pigtailed macaques (Macaca nemestrina).

Dystocia (difficult labor) is an important component of the management of nonhuman primates and results in significant fetal and maternal morbidity and increased use of veterinary resources. Dystocias can arise from abnormalities of the maternal pelvis or fetus or uncoordinated uterine activity. Although risk factors for stillbirths have been established in nonhuman primates, risk factors for dystocias have not. The objective of this study was to determine maternal and fetal risk factors for dystocia in macaques. Retrospective data were collected from 83 pigtailed macaques (Macaca nemestrina) diagnosed with dystocia. The diagnosis of dystocia was made based on clinical or pathologic evidence. Maternal records of age, reproductive history, experimental history, clinical records, and fetal birth weight and any applicable fetal necropsy reports were reviewed. The gestational age of the fetus, the infant's birth weight, total previous births by the dam, and the proportions of both viable delivery (inverse effect) and surgical pregnancy interventions (direct effect) in the dam's history generated a model that maximized the experimental variance for predicting dystocia in the current pregnancy and explained 24% of the dystocia deliveries. The number of total previous births and proportion of previous cesarean sections accounted for the greatest effect. This model can identify individual dams within a colony that are at risk for dystocias and allow for changes in breeding colony management, more intense monitoring of dams at risk, or allocation of additional resources.

Primary hepatic Mycobacterium tuberculosis complex infection with terminal dissemination in a pig-tailed macaque (Macaca nemestrina).

An adult, female, pig-tailed macaque (Macaca nemestrina) of Indonesian origin presented with profound weight loss, anemia (PCV, 29%; normal, 36% to 45%), hypoalbuminemia (1.0 g/dL; normal, 3.5 to 5.2 g/dL), elevated alkaline phosphatase (1990 U/L; normal, 26 to 98 U/L), and an elevated erythrocyte sedimentation rate (75 mm/h; normal, less than 20 mm/h). Abdominal ultrasonography demonstrated an enlarged liver with hyperechoic areas. Euthanasia was performed. Grossly, the liver had multifocal, effacing, white masses throughout and was enlarged with rounded edges. There were 2, small nodules in the right lung lobes. Histologically, the hepatic masses were densely fibrous-encapsulated granulomas with vast central necrosis. The lung nodules also were maturing granulomas, and one kidney and one atrium had small, early granulomas. Fite acid-fast stains of liver and lung revealed very few acid-fast bacilli. PCR analysis of paraffin-embedded liver identified Mycobacterium tuberculosis complex. Culture of the liver was negative twice. This macaque had 16 negative intradermal tuberculin skin tests over the course of 6 y. We hypothesize that the animal arrived with a latent hepatic or enteric infection that later recrudesced and disseminated. Primary hepatic mycobacteriosis is not a typical presentation of tuberculosis in macaques. Negative tuberculin skin tests can be seen with latent infections and extrapulmonary tuberculosis such as Pott disease. This case underscores the problems associated with current surveillance procedures and the risks associated with latent mycobacterial infections in macaques.

Serum biomarkers in a mouse model of bacterial-induced inflammatory bowel disease.

BACKGROUND: The diagnosis and classification of inflammatory bowel disease (IBD) require both clinical and histopathologic data. Serum biomarkers would be of considerable benefit to noninvasively monitor the progression of disease, assess effectiveness of therapies, and assist in understanding disease pathogenesis. Currently, there are limited noninvasive biomarkers for monitoring disease progression in animal IBD models, which are used extensively to develop new therapies and to understand IBD pathogenesis. METHODS: Serum biomarkers of early and late IBD were identified using multianalyte profiling in mdr1a(-/-) mice with IBD triggered by infection with Helicobacter bilis. The correlation of changes in these biomarkers with histopathology scores and clinical signs in the presence and in the absence of antibiotic treatment was determined. RESULTS: Serum levels of interleukin (IL)-11, IL-17, 10-kDa interferon-gamma-inducible protein (IP-10), lymphotactin, monocyte chemoattractant protein (MCP)-1, and vascular cell adhesion molecule (VCAM)-1 were elevated early in IBD. In late, more severe IBD, serum levels of IL-11, IP-10, haptoglobin, matrix metalloproteinase-9, macrophage inflammatory protein (MIP)-1gamma, fibrinogen, immunoglobulin A, MIP-3 beta (beta), VCAM-1, apolipoprotein (Apo) A1, and IL-18 were elevated. All late serum biomarkers except Apo A1 correlated with histopathology scores. Antibiotic treatment improved clinical signs of IBD and decreased mean serum values of many of the biomarkers. For all biomarkers, the individual pathology scores correlated significantly with individual serum analyte levels after treatment. CONCLUSIONS: Serum analyte measurement is a useful, noninvasive method for monitoring disease in a mouse model of bacterial-induced IBD.

Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration.

Huntington's disease (HD) is a fatal, dominantly inherited disorder caused by polyglutamine repeat expansion in the huntingtin (htt) gene. Here, we observe that HD mice develop hypothermia associated with impaired activation of brown adipose tissue (BAT). Although sympathetic stimulation of PPARgamma coactivator 1alpha (PGC-1alpha) was intact in BAT of HD mice, uncoupling protein 1 (UCP-1) induction was blunted. In cultured cells, expression of mutant htt suppressed UCP-1 promoter activity; this was reversed by PGC-1alpha expression. HD mice showed reduced food intake and increased energy expenditure, with dysfunctional BAT mitochondria. PGC-1alpha is a known regulator of mitochondrial function; here, we document reduced expression of PGC-1alpha target genes in HD patient and mouse striatum. Mitochondria of HD mouse brain show reduced oxygen consumption rates. Finally, HD striatal neurons expressing exogenous PGC-1alpha were resistant to 3-nitropropionic acid treatment. Altered PGC-1alpha function may thus link transcription dysregulation and mitochondrial dysfunction in HD.