A survey for a trypanocidal factor in primate sera

The sera of 21 different species of primates were surveyed for the presence of a trypanocidal factor to a monomorphic human serum-sensitive clone of Trypanosoma brucei gambiense (T.b.g.); human, gorilla, baboon (2 species), and the mandrill were found to contain this factor. The factor in all the sera is in the high density lipoprotein (HDL) fraction, and has similar modes of biological action. It has been shown that the human and gorilla trypanocidal factor share cross-reactive antigenic epitopes, but do not share similar cross-reactive epitopes with the baboon and mandrill factor. There was no relationship between the presence or absence of this factor and the primate's position on the phylogenetic tree. In addition, there was also no obvious correlation between the animals' preferred diet, and the presence or absence of trypanocidal activity. The evidence to date suggests that only African ground-dwelling primates that live in tsetse endemic areas contain the trypanocidal factor. It is assumed that this factor is involved in resistance of these primates to T.b.b. We believe that the host has developed trypanocidal substances as a result of selective evolutionary pressure by the African trypanosomes.     

Transgenic nonhuman primate models for human diseases: approaches and contributing factors

Nonhuman primates (NHPs) provide powerful experimental models to study human development,cognitive functions and disturbances as well as complex behavior,because of their genetic and physiological simi...     

Morphological differences between minicolumns in human and nonhuman primate cortex

Our study performed a quantitative investigation of minicolumns in the planum temporale (PT) of human, chimpanzee, and rhesus monkey brains. This analysis distinguished minicolumns in the human cortex from those of the other nonhuman primates. Human cell columns are larger, contain more neuropil space, and pack more cells into the core area of the column than those of the other primates tested. Because the minicolumn is a basic anatomical and functional unit of the cortex, this strong evidence showed reorganization in this area of the human brain. The relationship between the minicolumn and cortical volume is also discussed.     

Rabbit and nonhuman primate models of toxin-targeting human anthrax vaccines.

The intentional use of Bacillus anthracis, the etiological agent of anthrax, as a bioterrorist weapon in late 2001 made our society acutely aware of the importance of developing, testing, and stockpiling adequate countermeasures against biological attacks. Biodefense vaccines are an important component of our arsenal to be used during a biological attack. However, most of the agents considered significant threats either have been eradicated or rarely infect humans alive today. As such, vaccine efficacy cannot be determined in human clinical trials but must be extrapolated from experimental animal models. This article reviews the efficacy and immunogenicity of human anthrax vaccines in well-defined animal models and the progress toward developing a rugged immunologic correlate of protection. The ongoing evaluation of human anthrax vaccines will be dependent on animal efficacy data in the absence of human efficacy data for licensure by the U.S. Food and Drug Administration.     

MRI-guided dissection of the nonhuman primate brain: A case study

Numerous biochemical as well as electrophysiological techniques require tissue that must be retrieved very quickly following death in order to preserve the physiological integrity of the neuronal environment. Therefore, the ability to accurately predict the precise locations of brain regions of interest (ROI) and to retrieve those areas as quickly as possible following the brain harvest is critical for subsequent analyses. One way to achieve this objective is the utilization of high-resolution MRI to guide the subsequent dissections. In the present study, individual MRI images of the brains of rhesus and cynomolgus macaques that had chronically self-administered ethanol were employed in order to determine which blocks of dissected tissue contained specific ROIs. MRI-guided brain dissection of discrete brain regions was completely accurate in 100% of the cases. In comparison, approximately 60–70% accuracy was achieved in dissections that relied on external landmarks alone without the aid of MRI. These results clearly demonstrate that the accuracy of targeting specific brain areas can be improved with high-resolution MR imaging.     

Evolution of epitopes on human and nonhuman primate lymphocyte cell surface antigens

The T- and B-cell surface polypeptides detected by an international workshop panel of 100 mouse monoclonal antibodies (M.Ab) were biochemically defined by radioimmunoprecipitation. Eight T-cell-associated molecules and eight B-cell-associated molecules were identified by multiple antibodies in the panel. Clusters of antibodies specific for the same polypeptide were then compared for their reactivity against peripheral blood mononuclear cells (PBMC) from 11 nonhuman primate species. All the major T- and B-cell antigens present in humans were also expressed in some nonhuman primates. M.Ab to the same antigen were found to react with distinct epitope groups that differed in their phylogenetic distribution. Some epitopes were highly conserved, while other epitopes on the same molecule were only expressed in hominoids and were not detected in old world and new world monkeys. Our detailed analysis of the phylogeny of 37 T-cell antigen epitopes on ten different molecules revealed there was no clear correspondence between the number of epitopes shared and evolutionary distance. Rather the data suggest that parallelism with back mutation may be a common mechanism in the evolution of T-cell antigens. The data also show that the tissue distribution of T-cell antigens can differ between primate species; for example, M.Ab to human Tp45 Tla-Qa-like antigens that did not react with human PBMC did react with PBMC from new world monkeys.     

Nomegestrol acetate and vascular reactivity: nonhuman primate experiments

Prevention of coronary artery disease has been recognized as a major benefit of estrogen replacement therapy (ERT) in postmenopausal women. However, endometrial hyperplasia induced by unopposed ERT has raised important safety concerns. Progesterone or synthetic progestins have been used in combined hormone replacement therapy (HRT) to prevent endometrial cancer risk. Therefore, a major concern has been to ensure that the vascular beneficial effects of estrogens are not opposed when combined with progestins. Nomegestrol acetate (NOMAC) is an orally active progestin widely prescribed for HRT. Its vascular effects were evaluated in two models of coronary vascular reactivity in primates: 1) the paradoxical vasoconstriction to acetylcholine (Ach) coronary infusion after 5 months of mildly atherogenic diet in ovariectomized (OVX) Cynomolgus monkeys and 2) the pharmacologically evoked coronary vasospasm in the OVX Rhesus monkey. In the first model, after 3 months of continuous oral administration in the diet at 0.1 mg/kg/day, E2 prevented the paradoxical response to Ach, alone as well as combined with 0.25 mg/kg/day NOMAC, whereas NOMAC counteracted the endometrial stimulation. In the second model, after one artificial cycle consisting of 28 days of E2 subcutaneous (s.c.) implant and of daily oral gavage with 1 mg/kg/day of NOMAC for the last 14 days, no vasospasm (0 of 11 tested animals) occurred when the complete challenge protocol, including serotonin and the thromboxane agonist U46619, was administered to OVX Rhesus monkeys. In the balanced crossover design, identical artificial cycles with medroxyprogesterone acetate (MPA) at the same dose resulted in 7 vasospasms in 12 animals. In parallel, effective progestative activity was demonstrated by a secretory pattern in endometrial sections obtained at the end of the cycle. In these two nonhuman primate cardiovascular models, NOMAC did not have the negating effects observed with MPA.     

Government regulation of nonhuman primate facilities

Myriad international, federal, and state laws, regulations, rules, guidelines, and standards directly affect the activities of all nonhuman primate research facilities. Federal regulations alone encompass every aspect of facility operations. They govern the procurement, possession, handling, care, and utilization of nonhuman primates, the design, construction, maintenance, and operation of the facility, and the occupational and environmental protection afforded not only facility personnel, but also the general public. Proper management of a nonhuman primate facility depends on continual monitoring of constantly changing laws and regulations applicable to the type of facility operated and research conducted. An in-house compliance assurance program is necessary to assure conformance with pertinent regulations.     

Human Pb,human post-Pb,and nonhuman primate Pb proteins: Immunological and biochemical relationships

The isolation and characterization of a protein from human parotid saliva termed the "post-Pb protein" is described. By several criteria, this protein is closely related to the human Pb proteins. When reacted against antisera to human Pb protein in double diffusion, the post-Pb protein is found to be related to the Pb proteins by lines of identity. However, when the partial N-terminal amino acid sequences of the post-Pb protein and Pb proteins are compare, the sequences are not identical. Because of the similarity in size of the Pb and post-Pb proteins and because of the observed sequence differences, any product-precursor relationship between the Pb and post-Pb proteins is unlikely. The post-Pb protein probably is the product of a genetic locus different from the Pb locus. Two additional species of nonhuman primates (Papio papio and P. sphinx) have been found to have Pb proteins electrophoretically similar to these found in the rhesus monkey and differing from those in the human. The isolated Pb proteins of the rhesus monkey have been found to have close biochemical and immunological relationships to the human Pb proteins.     

Disruption of human TRIM5alpha antiviral activity by nonhuman primate orthologues

TRIM5 is a determinant of species-specific differences in susceptibility to infection by retroviruses bearing particular capsids. Human immunodeficiency virus type 1 (HIV-1) infection is blocked by the alpha isoform of macaque TRIM5 (TRIM5alpha(rh)) or by the product of the owl monkey TRIM5-cyclophilin A gene fusion (TRIMCyp). Human TRIM5alpha potently restricts specific strains of murine leukemia virus (N-MLV) but has only a modest effect on HIV-1. The amino termini of TRIM5 orthologues are highly conserved and possess a coiled-coil domain that promotes homomultimerization. Here we show that heterologous expression of TRIM5alpha(rh) or TRIMCyp in human cells interferes with the anti-N-MLV activity of endogenous human TRIM5alpha (TRIM5alpha(hu)). Deletion of the cyclophilin domain from TRIMCyp has no effect on heteromultimerization or colocalization with TRIM5alpha(hu) but prevents interference with anti-N-MLV activity. These data demonstrate that TRIM5 orthologues form heteromultimers and indicate that C-terminal extensions alter virus recognition by multimers of these proteins.     

Polymorphism of glycophorins in nonhuman primate erythrocytes

Using immunoblotting techniques and polyclonal antisera to human erythrocyte glycophorin, we show that erythrocytes of several species of nonhuman primates, including representatives of anthropoid apes (19 chimpanzees, 3 gorillas, 6 orangutans, and 3 gibbons) and Old World monkeys (3 baboons, 5 rhesus monkeys, and 6 cynomologus macaques), contain human glycophorin-like molecules. Each species displays a unique glycophorin profile; in anthropoid apes the profile is more complex than in Old World monkeys and more similar to that seen in humans. The chimpanzee was the only species in which human -like glycophorin was detected but it differed from its human counterpart in electrophoretic mobility and reaction with M-specific monoclonal antibody. In contrast to humans, highly polymorphic glycophorin profiles were observed in each species of anthropoid apes and three distinct patterns were defined in each. No such polymorphism has been found so far among the Old World monkeys in the limited number of animals studied. The major glycophorins in all species but the chimpanzees failed to react with M- or N-specific monoclonal antibodies, suggesting structural differences from the human within the amino terminal regions. The reaction with the minor glycophorins showed inter- and intraspecies variability. All glycophorins, except -like glycophorin in the chimpanzee, reacted with the antiserum to the carboxyl terminal fragment of human glycophorin, indicating a structural relation to the human in this region. An unexpected correlation was observed, in the chimpanzee, between the patterns of electrophoretically resolved glycophorins and the V-A-B-D blood-group phenotypes, allowing the assignment of each determinant to specific glycophorin bands. The basis for the differences observed between human and nonhuman primate glycophorins is not clear but the possibilities include a common nonpolymorphic ancestor and differences in selective pressures.This research was supported by National Institutes of Health Grant 5 RO1 GM16389.     

The evolution of nonhuman primate social behavior

A review of the recent literature concerning evolutionary mechanisms and possible genetic contributions to social behavior reveals a concentration on function rather than mechanism. Although functional consequences may influence future genetic changes in a population, they do not necessarily reflect evolutionary history. More important, genes cannot code for functions. Only when the anatomical structures and behavioral patterns of individuals are described can we study genetic contributions to social organization. Discussions of function in the abstract, without specification of mechanism, do not fall within the realm of scientific testing.     

High quality sperm for nonhuman primate ART: Production and assessment

Factors that affect sperm quality can include method of semen collection, conditions for capacitation and whether or not agglutination is present. Media and procedures for sperm washing can also impair or improve sperm function in assisted reproductive technologies. For example, the removal of seminal fluid through large volume washing is required to eliminate decapacitation activity of seminal plasma. The forces involved with centrifugation and the metabolic stress of tightly pelleting sperm during washing procedures can have deleterious results. In contrast to human sperm, sperm from the most commonly used species of nonhuman primates, rhesus and cynomolgus macaques, do not spontaneously capacitate in vitro; rather, chemical activation with dibutryl cyclic AMP and caffeine is required. Recognizing motility patterns of non-activated and activated sperm can be accomplished with simple observation. After activation, sperm agglutination sometimes occurs and can interfere with sperm binding to the zona pellucida. Because nonhuman primate oocytes require a large investment to produce and currently, each animal can be hormonally stimulated a limited number of times, it is important to have means to evaluate quality prior to using sperm from a new male for in vitro fertilization. Methods for producing live, acrosome reacted sperm may also have application for ICSI. Because many genetically valuable males are now being identified, it may be necessary to individualize sperm preparation to accommodate male-to-male variation.