Sherry A. Klumpp

Brain weight throughout the life span of the chimpanzee

Studies on human postmortem material report lower brain weights in older than in younger cohorts, whereas there is no apparent change with age in the rhesus monkey. In view of these contrasting results, we examined the pattern of brain weight across the life span in the chimpanzee, one of the closest biological relatives of humans. To place the study in context of the empirical life expectancy of the chimpanzee, we first performed a survival analysis on data from 275 chimpanzees that were maintained in the colony of the Yerkes Primate Center. The survival analysis revealed the maximum life spans of female and male chimpanzees to be about 59 and 45 years, respectively. We examined fresh brain weights from 76 chimpanzees ranging in age from birth to 59.4 years of age. The brains were taken from 9 infants (birth to 1 year of age), 25 juveniles (1–7 years), 13 adolescents (7–15 years), 21 young adults (15–30 years), and 8 old adults (over 30 years). Adult brain weight was achieved by the age of 7 years. The adolescent and young adult chimpanzees had the largest brain weights; in these two age groups combined, the mean brain weight (± standard deviation) was 368.1 g (±37.3) for females (n = 17) and 405.6 g (±39.4) for males (n = 17). This sex difference was statistically significant (P < 0.01). Simple linear regression performed on the combined material from females and males aged 7 years and older revealed a decline in brain weight with advancing age of 1.1g/year (P < 0.05). When the effect of sex on brain weight was statistically controlled for, the loss of brain weight with age was 0.9 g/year (P = 0.07). These results suggest that brain weight declines moderately with age in the chimpanzee as it does in humans. J. Comp. Neurol. 409:567–572, 1999.

Nonhuman Primate Models for Evaluation of AIDS Therapya

Infection of macaque monkeys with simian immunodeficiency virus (SIV) has been established as an excellent animal model system for studying the pathogenesis of an HIV-like virus and for evaluating newly developed antiretroviral drugs and vaccines. Based on their genetic, antigenic, and biologic properties, the simian immunodeficiency viruses are the closest known relatives of the human AIDS viruses, and experimental infection of macaque monkeys results in a disease that is remarkably similar to human AIDS. Infected macaques show diarrhea, weight loss, hematologic abnormalities including lymphopenia and thrombocytopenia, lymphadenopathy/lymphoid hyperplasia that progresses to lymphoid depletion, immunosuppression with marked reduction in CD4+ cells and in the CD4+/CD8+ cell ratio, and opportunistic infections. A majority of such macaques die from an AIDS-like disease within one to three years of infection. An acutely lethal variant of SIV has been identified that results in death in susceptible macaques within 7-12 days of infection. Preliminary prophylactic treatment trials with AZT in macaque monkeys exposed to the acutely lethal SIV variant indicate that some protection is provided when AZT treatment is initiated within 24 hours of virus exposure. Other studies with the more chronic SIV infection model, however, failed to show any prophylactic efficacy of CS-87, AZT, D4T, or FDT.

Brain weight does not decrease with age in adult rhesus monkeys

Cross-sectional studies on adult human autopsy material have shown that younger cohorts have heavier brains than older groups. We sought to determine whether a similar pattern is present in the rhesus monkey, a species that serves as a useful model of human brain and cognitive aging. Data were obtained from necropsies of 399 rhesus monkeys (180 females; 219 males), of ages covering the entire adult lifespan of this species. In addition to fresh brain weight, variables considered were age, sex, body weight, heart weight, identity of the prosector, and circumstance of death. Initial bivariate analyses revealed a significant sex difference in brain weight (mean for males: 96.1 g; for females: 86.1 g; p < 0.001), as well as significant correlations of brain weight with body weight (r = 0.20, p < 0.01 for females; r = 0.27, p < 0.001 for males), and heart weight (r = 0.27, p < 0.001 for females; r = 0.38, p < 0.001 for males). Identity of prosector, circumstance of death, and age were not significantly related to brain weight in bivariate analyses. Multiple linear regression, controlling for possible confounding effects of body weight and sex, also suggested that brain weight is stable throughout adulthood in the rhesus monkey.

Molecular Evidence for Rhesus Lymphocryptovirus Infection of Epithelial Cells in Immunosuppressed Rhesus Macaques

ABSTRACT Epstein-Barr virus (EBV) is a human oncogenic herpesvirus associated with epithelial cell and B-cell malignancies. EBV infection of B lymphocytes is essential for acute and persistent EBV infection in humans; however, the role of epithelial cell infection in the normal EBV life cycle remains controversial. The rhesus lymphocryptovirus (LCV) is an EBV-related herpesvirus that naturally infects rhesus macaques and can be used experimentally to model persistent B-cell infection and B-cell lymphomagenesis. We now show that the rhesus LCV can infect epithelial cells in immunosuppressed rhesus macaques and can induce epithelial cell lesions resembling oral hairy leukoplakia in AIDS patients. Electron microscopy, immunohistochemistry, and DNA-RNA in situ hybridization were used to identify the presence of a lytic rhesus LCV infection in these proliferative, hyperkeratotic, or parakeratotic epithelial cell lesions. These studies demonstrate that the rhesus LCV has tropism for epithelial cells, in addition to B cells, and is a relevant animal model system for studying the role of epithelial cell infection in EBV pathogenesis.

Chemotherapy-induced hemolytic uremic syndrome: description of a potential animal model.

Hemolytic uremic syndrome (HUS) is an uncommon complication of chemotherapy that contributes to the morbidity of oncology and bone marrow transplant patients. The pathogenesis is not well understood and no established clinical animal model exists. We studied four rhesus monkeys (RM) that developed fatal HUS following high‐dose chemotherapy. Microangiopathic hemolytic anemia (pre‐Hct 40% and day 5–8 Hct 31 % (P <.05), increased BUN (168 mg/dl), creatinine (8.2 mg/dl), and lactate dehydrogenase (1458 IU/L) (mean day 5–8 measurements) were observed. Platelets counts decreased to 39±15 × 109/l from a mean of 397±31 × 109/L (P < .0001). vWF, ATIII, thrombin:anti‐thrombin complex (T:AT) and prothrombin fragment F1.2 levels were not different from a control group (N = 2). The data presented describe chemotherapy‐induced HUS with typical clinical and laboratory features which may provide an animal model for the study of this important syndrome.

Carcinomas, Gastrointestinal Tract

Gastric carcinomas in macaques range from single, large, firm, gray-white masses (Kimbrough 1966) to multiple nodules measuring up to 2.5 cm in diameter (Schmey 1914). Metastasis to regional lymph nodes or the liver occurred in two of four cases (Schmey 1914; Kluver, cited in Ruch 1959) and one of four cases (Kluver, cited in Ruch 1959), respectively.

Chromobacteriosis, Nonhuman Primates

Gross pathologic changes associated with Chromobacterium violaceum infection may be evident in multiple organ systems, including the lungs, liver, spleen, lymph nodes, and kidneys. Affected organs are often swollen and congested with scattered petechial hemorrhages, and con¬tain variable sized areas of necrosis that range from pinpoint to 3–4 cm in diameter. When sectioned, larger lesions are often cavitary and contain a yellowish-white semifluid exudate (Fig. 141).