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PubMed1993

Blood group A and B glycosyltransferases in nonhuman primate plasma.

The products of the blood group A and B genes, alpha-3-N-acetyl-D-galactosaminyltransferase (A-transferase) and alpha-3-D-galactosyltransferase (B-transferase) in 83 plasma samples of 24 species of nonhuman primates were investigated by enzymatic conversion of human group O red cells into A or B active cells. The conversions were demonstrated by the anti-A and anti-B agglutinability of the red cells. The plasma from group A and B anthropoid apes converted untreated group O human red cells into A and B active cells in the presence of UDP-N-acetyl-D-galactosamine and UDP-D-galactose, respectively. When papain-treated O red cells were used as an acceptor, A and B conversions by plasma glycosyltransferases of prosimians, New and Old World monkeys were detected. Most of the plasma from nonhuman primates contained A- or/and B-transferase activities that correspond to the A and B antigens expressed in the red cells. The A and B enzyme activities from nonhuman primates were almost equivalent to those from human A and B subgroups or variants. H antigen in the red cells of pig-tailed monkeys could be converted to A and B active ones by using plasma samples from man and nonhuman primates as enzyme sources. The optimal pH of A-transferases from Old World monkeys and human group A2 were 7.4 and 7.6, and from anthropoid apes and human group A1 they were 6.6 and 6.4, respectively. The pH optima of B-transferases from nonhuman primates and man distributed at 6.2-6.5.

ABO Blood-Group System↗
PubMed2005

Environmental enrichment for nonhuman primates: theory and application.

Investigators have an obligation to promote the psychological well-being of nonhuman primates used in research. Considerable emphasis has been placed on providing nonhuman primates with enriched environments as a means to achieve this objective. A framework is provided that consists of a set of hypotheses about well-being, and the extent to which exposure to various enrichment devices and procedures actually promotes well-being is evaluated. Two hypotheses are concerned with fostering species-typical behavior: use (versus nonuse) of the enrichment, and whether use of enrichment helps normalize other aspects of the behavioral repertoire. Two additional hypotheses are concerned with abnormal behavior: whether currently existing enrichment lowers levels of abnormal behavior, and whether it prevents the behavior. This framework is applied to various enrichment strategies ranging from toys and foraging devices to social interaction. Most devices are used by nonhuman primates and thus constitute an important way to enrich the captive environment. However, enrichment devices vary as to their effectiveness in normalizing the behavioral repertoire and eliminating abnormal behavior. Only social contact satisfies the goal of promoting a wide variety of species-typical activities while at the same time reducing or preventing the development of abnormal behavior.

Animal Husbandry↗
PubMed2002

A life-supporting technique of renal allotransplantation in Macaca fascicularis to evaluate novel immunosuppressive drugs in nonhuman primates.

BACKGROUND: The use of nonhuman primates in preclinical transplantation studies is becoming more common. This report details complete procedures developed for a successful life-supporting kidney allotransplantation program using the cynomolgus monkey (Macaca fascicularis). MATERIALS AND METHODS: All transplants were performed in wild-caught, ABO-matched, MLR-mismatched adult males. Transplant procedures were staggered: an animal first served as a donor, was allowed to recover for 4 weeks, and was subsequently used as a recipient. The kidney was flushed in situ while the aorta was briefly cross-clamped. The graft was implanted heterotopically end-to-side in the right iliac fossa using microsurgical techniques. An ureteroneocystostomy was constructed; a telemetry probe was inserted into the aorta, and the remaining native kidney was removed. RESULTS: Sixty-two transplants were performed in 6.9 +/- 0.1 kg animals. Operating times in the donor and recipient were 126 +/- 3 and 166 +/- 5 min, respectively. The cold ischemia time was 55 +/- 1 min. There were no intraoperative deaths. Postoperative complications were observed in six (9.7%) monkeys and consisted of one early renal arterial thrombosis and five ureteral complications (two of which were successfully repaired). Transplants were ultimately successful in 93.6% (58/62) of cases. Immediate kidney function was satisfactory, with a mean serum creatinine of 1.7 +/- 0.2 mg/dL and a mean urine output of 140 +/- 15 ml on postoperative day 7. CONCLUSION: Life-supporting kidney transplantation in cynomolgus macaques is a demanding operation that requires great attention to details. Precise surgical techniques, telemetric monitoring, ultrasound surveillance, and aggressive, early, postoperative fluid resuscitation produced a 94% success rate.

Animals↗
PubMed2005

Hormonal influences on sexually differentiated behavior in nonhuman primates.

Sexually dimorphic behavior in nonhuman primates results from behavioral predispositions organized by prenatal androgens. The rhesus monkey has been the primary primate model for understanding the hormonal organization of sexually dimorphic behavior. Historically, female fetuses have received high prenatal androgen doses to investigate the masculinizing and defeminizing effects of androgens. Such treatments masculinized juvenile and adult copulatory behavior and defeminized female-typical sexual initiation to adult estrogen treatment. Testosterone and the nonaromatizable androgen, 5alpha-dihydrotestosterone, produced similar effects suggesting that estrogenic metabolites of androgens are not critical for masculinization and defeminization in rhesus monkeys. Long duration androgen treatments masculinized both behavior and genitalia suggesting that socializing responses to the females' male-like appearance may have produced the behavioral changes. Treatments limited to 35 days early or late in gestation differentially affected behavioral and genital masculinization demonstrating direct organizing actions of prenatal androgens. Recent studies exposed fetal females to smaller doses of androgens and interfered with endogenous androgens using the anti-androgen flutamide. Low dose androgen treatment only significantly masculinized infant vocalizations and produced no behavioral defeminization. Females receiving late gestation flutamide showed masculinized infant vocalizations and defeminized interest in infants. Both late androgen and flutamide treatment hypermasculinized some male juvenile behaviors. Early flutamide treatment blocked full male genital masculinization, but did not alter their juvenile or adult behavior. The role of neuroendocrine feedback mechanisms in the flutamide effects is discussed. Sexually differentiated behavior ultimately reflects both hormonally organized behavioral predispositions and the social experience that converts these predispositions into behavior.

Androgen Antagonists↗
PubMed2002

Immunomodulatory effects of estrogen and progesterone replacement in a nonhuman primate model.

A novel postmenopausal nonhuman primate model consisting of healthy young and old ovariectomized rhesus macaques was used to assess the short-term immunomodulatory effects of transdermally administered estrogen and progesterone. Specifically, we determined estrogen- and progesterone-induced changes in absolute numbers of circulating lymphocytes (B lymphocytes, CD4+ lymphocytes, and CD8+ lymphocytes) as well as lymphocytes expressing the activation markers CD25 and CD69. In addition, we assessed B and T lymphocyte activity, i.e, immunoglobulin (Ig) and interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMCs). In general, treatment with estrogen or progesterone resulted in decreased lymphocyte numbers and in down-modulation of activation markers. In addition, hormone replacement resulted in a decreasing trend for PBMC IFN-gamma production, whereas PBMC Ig production was minimally affected. Hormone treatment seemed to influence young and old animals differently, with the young animals appearing more susceptible to its immune system-related effects. These results indicate that, in our animal model exogenously administered hormones may dynamically interact with the immune system, resulting in in vivo modulation of lymphocyte numbers and activity.

Adjuvants, Immunologic↗
PubMed1986

Social relationships and social cognition in nonhuman primates.

Complex social relationships among nonhuman primates appear to contribute to individual reproductive success. Experiments with and behavioral observations of natural populations suggest that sophisticated cognitive mechanisms may underlie primate social relationships. Similar capacities are usually less apparent in the nonsocial realm, supporting the view that at least some aspects of primate intelligence evolved to solve the challenges of interacting with conspecifics.

Animals↗
PubMed1983

Studies on the production of low density lipoproteins by perfused livers from nonhuman primates. Effect of dietary cholesterol.

Nonhuman primates consuming diets containing cholesterol develop coronary artery atherosclerosis that we have found to be highly correlated with an increase in the size and cholesteryl ester content of plasma low density lipoproteins (LDL). The present studies were designed to determine whether the enlarged plasma LDL are produced directly by the liver of cholesterol-fed monkeys. African green monkeys were fed a diet containing 40% of calories as butter fat and either 0.16 mg cholesterol/kcal (control diet) or 0.78 mg cholesterol/kcal (test diet). The livers of these monkeys were perfused by recirculation with a lipoprotein-free medium for 4 h. The rate of accumulation of perfusate cholesterol was linear and greater in liver perfusates from test diet-fed vs. control diet-fed monkeys and was positively correlated with both the plasma cholesterol concentration and LDL size in the donor animal. All perfusate d less than 1.063 g/ml lipoprotein subfractions from livers of test diet-fed monkeys were enriched in cholesteryl ester severalfold over the corresponding subfractions from control diet-fed monkeys and contained only the larger form of apolipoprotein B typical of plasma LDL. However, the perfusate lipoproteins in the LDL density range did not have an average size or composition typical of LDL from plasma. Rather, they were relatively enriched in phospholipid and unesterified cholesterol and were deficient in cholesteryl esters. In addition, perfusate high density lipoproteins were discoidal particles. These data show that the enzyme lecithin:cholesterol acyltransferase (LCAT) was essentially inactive in these perfusates and, as a result, the dietary cholesterol-induced enrichment of perfusate d less than 1.063 g/ml lipoproteins with cholesteryl esters probably resulted from increased hepatic secretion of cholesteryl esters and not from modification of lipoproteins by LCAT during recirculating perfusion. In spite of this increase, enlarged cholesteryl ester-rich LDL were not found in the perfusate, suggesting that large molecular weight plasma LDL are not directly secreted by the liver but instead probably result from further intravascular metabolism of cholesteryl ester-enriched hepatic precursor lipoproteins.

Animals↗
PubMed1992

A comparative study of natural killer cell activity, lymphoproliferation, and cell phenotypes in nonhuman primates.

Three different species of nonhuman primates (baboons [Papio hamadryas], rhesus monkeys [Macaca mulatta], and African green monkeys [Cercopithecus aethiops]) were evaluated for their natural killer cell activity, and for the ability of their peripheral blood mononuclear cells to proliferate in response to known mitogens (concanavalin A, phytohemagglutinin, and pokeweed mitogen) and to react with a panel of mouse monoclonal antibodies directed against human leukocyte surface antigens. Rhesus monkeys displayed the highest natural killer cell cytotoxic activity (185.7 +/- 33 lytic units) compared with those of baboons (83.8 +/- 19 lytic units) and of African green monkeys from West Africa (39.08 +/- 8 lytic units) and from the Caribbean basin (37.9 +/- 9 lytic units). No correlation was observed between the natural killer cell cytotoxic activity and the percentage of CD16+ natural killer cells among the three species studied. High spontaneous proliferative capacity was observed in African green monkeys obtained from West Africa compared with those of the other species studied. Although no significant differences were noted in T and B cell mitogen-induced in vitro proliferation, baboon mononuclear cells were less responsive to concanavalin A (stimulation index of 16 +/- 3 [mean +/- standard error of mean]) than to phytohemagglutinin (stimulation index of 47 +/- 12). However, rhesus and African green monkey cells proliferated more efficiently in response to concanavalin A. Unlike in human beings where the ratio between helper-inducer (CD4+) and cytotoxic-suppressor (CD8+) T-lymphocytes is generally greater than 1, the CD4+/CD8+ ratios in baboons and rhesus and African green monkeys were 0.58, 0.69, and 0.35, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of recombinant human granulocyte-macrophage colony-stimulating factor on platelet survival and activation using a nonhuman primate model.

In humans and nonhuman primates, the in vivo administration of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) consistently results in marked increase of megakaryocyte ploidy and size similar to that observed with interleukin-6 (IL-6). However, whereas the administration of IL-6 also results in an increase in circulating platelets, there is no predictable corresponding increase in peripheral blood platelets following treatment with rhGM-CSF. To determine whether the failure of rhGM-CSF to produce thrombocytosis is secondary to cytokine-related increased platelet activation and consumption in vivo, we quantified autologous platelet survival time and in vivo platelet activation before and during 5 days of administration of rhGM-CSF to two rhesus monkeys. Platelet survival was measured using autologous platelets labeled with 111Indium-oxine. Platelet activation was assessed by flow cytometric determination of the expression of the major platelet membrane glycoprotein (GP) IIb/IIIa complex, and an activation-dependent epitope on GPIIb/IIIa (recognized by monoclonal antibodies [MABs] LJ-P4 and PAC1, respectively). Platelet activation was also assessed by dose-response aggregometry using adenosine diphosphate (ADP). While megakaryocyte ploidy increased during rhGM-CSF administration, peripheral platelet counts were 418 x 10(9)/L and 525 x 10(9)/L before and 402 x 10(9)/L and 508 x 10(9)/L during cytokine treatment in animals 1 and 2, respectively. No changes were observed in the mean platelet volume. 111Indium-labeled platelet recovery in circulation was similar before (94.7%, 91.8%) and during (92.9%, 92.8%) rhGM-CSF administration, which indicates that cytokine-related in vivo sequestration of platelets does not occur. Autologous platelet survival was 5.6 and 6.2 days before and 5.0 and 5.4 days during the rhGM-CSF treatment (p = 0.07), without significant change in the corresponding platelet turnover rate (derived from the platelet count and survival time). The flow cytometric analysis showed no increase in the binding of either LJ-P4 or PAC1 MABs to the platelet membrane during rhGM-CSF administration. The aggregometry studies demonstrated similar concentrations of ADP inducing half-maximal aggregation (ED50). Overall, the above data indicate that treatment with rhGM-CSF is not associated with in vivo activation, sequestration, or increased consumption of platelets. The data suggest that the failure of rhGM-CSF-stimulated megakaryocytes to increase peripheral platelet count is a manifestation of ineffective megakaryocytopoiesis resulting from inability to increase platelet delivery to the circulation.

Animals↗
PubMed1997

Viral infections of nonhuman primates.

Approximately 53,000 serologic tests and viral isolation studies were performed on 1,700 nonhuman primate specimens for evidence of past and/or current viral infection. Information, other than the requested test, generally was not provided with the specimen. This lack of information does not permit any attempt at interpretation of results. Requested testing included a large number of diverse viral agents in approximately 40 primate species. The resulting data are in keeping with those of previous studies and offer an insight into the needs of colony management, as well as some general information on the overall frequency of infection with the indicated viruses. Inasmuch as the results represent testing of single specimens, they are not to be construed as "diagnostic," and simply indicate past infection as represented by the presence of antibody in the test animal. Viral isolation results are listed, and the number of positive results versus the number of animals tested emphasizes the limitations of the procedure. Investigations such as these continue to assist in the maintenance of healthy nonhuman primate colonies. This information also supports continued use of nonhuman primates for research in human viral infections and may be helpful in terms of animal selection for use in xenotransplants.

Animals↗
PubMed1981

The prostate of the nonhuman primate: normal anatomy and pathology.

The caudal and cranial prostate of different species of nonhuman primates were examined for histologic characteristics and pathological abnormalities. One hundred specimens from 12 species were represented. Among the pathologies found were: 1) cystic hyperplasia; 2) fibromuscular hyperplasia; 3) squamous metaplasia; 4) chronic and acute bacterial prostatitis; 5) prostate adenocarcinoma; and 6) other miscellaneous pathologic changes. A historical review of histological characteristics and pathological abnormalities of the nonhuman primate prostate is given. Based upon findings in this study, anatomical similarity of the caudal lobe of the prostate to the peripheral zone of the prostate in humans as described by McNeal is found. In the patas monkey the relationship of the cranial and caudal lobe suggests strongly the relationship seen between the central and peripheral zones in man. The case of prostatic adenocarcinoma described has only been reported in one other nonhuman primate.

Animals↗
PubMed1983

Selective myocardial cell necrosis in nonhuman primates.

A retrospective study was performed to describe the histologic stages of selective myocardial cell necrosis (SMCN) in nonhuman primates, and to compare the incidence of SMCN in two groups of nonhuman primates. Myocardial tissues taken at the time of autopsy from 50 primates at an experimental center were compared with similar tissues from 50 primates housed in a breeding colony. SMCN was confirmed in 20% of the experimental primates and 30% of the breeding primates, proportions that were not significantly different. The incidence and histologic characteristics of SMCN in nonhuman primates were similar to those described in humans, and resembled the lesion produced in experimental primates by administration of catecholamines of by hypokalemia.

Animals↗
PubMed2005

Nonhuman primate embryonic stem cells as a preclinical model for hematopoietic and vascular repair.

Stem cell-based regenerative medicine therapies have been touted recently as a novel therapeutic approach to treat and cure a wide range of diseases. Both adult and embryonic stem (ES) cells can serve as important sources of precursor cells to derive more mature cells potentially utilized for clinical applications. Nonhuman primates have proven useful as a preclinical model, as demonstrated in studies of hematopoietic cell transplantation, gene therapy, and other areas. The derivation of nonhuman primate ES cells now provides an optimal resource to characterize and test ES cell-based therapies prior to trials with human ES cells. This review describes work to define strategies and mechanisms to derive blood and endothelial cells from nonhuman primate ES cells isolated from various species. Preclinical testing that solely relies on studies of putative therapeutic cells derived from mouse ES cells transplanted into other mice, or analyses of human ES cell-derived cells transplanted into immunodeficient or immunosuppressed rodents may not be predictive of efficacy in subsequent human trials. However, future testing using nonhuman primate ES cell-derived therapeutic cells done as an allogeneic transplant may best predict success for subsequent studies using human ES cells. Therefore, additional research on nonhuman primate ES cells, in addition to work on mouse and human ES cells, is greatly needed to facilitate clinical translation of new stem cell treatments.

Animals↗
PubMed2002

Genetic management of nonhuman primates.

Genetic management is widely recognized as a critical component of the overall management of captive nonhuman primate colonies which produce animals for biomedical research. In this paper, we review the roles of conservation-oriented genetic management, research-oriented genetic management, genetic management at the level of taxomomic class, genetic management at the level of the population, and quantitative genetic analysis in comprehensive genetic management programs for nonhuman primate colonies. We conclude that genetic management is crucial for maintaining nonhuman primate populations suitable for genetic research on normal and disease-related phenotypes. In addition, for research programs that do not have specific genetic objectives, genetic management is essential to facilitate the selection of samples of well-matched unrelated animals for experimental purposes.

Animals↗
PubMed1988

Characterization of basophil-like cells derived from nonhuman primate bone marrow.

In order to determine whether mast cells or basophils could be derived from nonhuman primate bone marrow, cells from bone marrow aspirates were cultured in the presence of concanavalin A-stimulated nonhuman primate spleen cell supernatants (CAS). Culture conditions were identical to those used for culturing mucosal-like mast cells from mouse bone marrow. In this situation, basophil-like cells (BLC) could be identified in liquid cultures and averaged 14-19 microM in size, were round or oval in appearance, had lobulated nuclei, and contained less than 100 metachromatically staining granules per cell. By electron microscopy, granules had dense oval or semilunar cores with surrounding fibrous whorls. BLC were peroxidase positive, chloroacetate esterase negative, stained positively with acid toluidine blue, and contained 0.1-0.3 pg histamine per cell. BLC expressed IgE receptors and were Leu 5b and Leu 16 negative. IgE-sensitized BLC released histamine after stimulation with antihuman IgE or the calcium ionophore A23187. [35S]-labeled proteoglycans were degraded with chondroitinase ABC but not with heparinase, indicating the absence of heparin in BLC. Thus, culture conditions that include the use of CAS and lead to the growth of mast cells from rodent bone marrow result in the growth of BLC from nonhuman primate bone marrow. These observations suggest that fundamental differences exist in the type of histamine containing cells that arise from rodent and primate bone marrow when such bone marrow cells are cultured under identical conditions.

Animals↗
PubMed2002

Use of the progestin challenge test in nonhuman primates (Macaca fascicularis).

OBJECTIVE: To determine whether the progestin challenge test (PCT) would provide a reliable, noninvasive indicator of endometrial stimulation in nonhuman primates. DESIGN; Randomized, 2x2, crossover study. SETTING; Nonhuman primates (Macaca fascicularis) in an academic research environment. PATIENT(S): Adult, surgically postmenopausal, female cynomolgous macaques (n = 27) were studied. INTERVENTION(S): Females were randomly assigned to receive estradiol (n = 14; 0.028 mg/kg body weight) or vehicle (n = 13) daily. All animals were administered two PCTs in a crossover study design using two doses (0.28 mg/kg or 0.56 mg/kg body weight) of medroxyprogesterone acetate (MPA). MAIN OUTCOME MEASURE(S): Incidence and severity of withdrawal bleeding and serum estradiol (E(2)) and progesterone (P(4)) levels were evaluated. RESULT(S): Estradiol treatment resulted in endometrial "withdrawal" bleeding in all but one instance. Females receiving daily doses of E(2) exhibited a significantly greater (P<.01) incidence, severity, and duration of withdrawal bleeding compared to control animals. Of the five positive responses observed in the control females, four occurred when the higher dose of MPA was administered. CONCLUSION(S): These results indicate that the PCT is a useful, noninvasive method for determining the presence of endometrial stimulation in nonhuman primates.

Animals↗
PubMed1994

Comparison of nonhuman primate antibodies against Haemophilus influenzae type b polysaccharide with human antibodies in oligoclonality and in vivo protective potency.

Nonhuman primates are often used as a model for studying vaccines for humans. However, it is not always clear how closely the antibody responses in these species mimic human responses. Recent studies have characterized the human antibody response to Haemophilus influenzae type b (Hib) in great detail. In this study, we have compared the antibody response to Hib of humans with those of other primates. Studies of isoelectric points and V kappa subgroup usage show that, like humans, nonhuman primates produce oligoclonal antibodies. Also, monkey antibodies to the Hib polysaccharide are as protective as human antibodies in an in vivo model of Hib infection. Thus, we conclude that nonhuman primates produce antibodies to Hib polysaccharide that are structurally and functionally similar to human antibodies and are a good model for testing human vaccines.

Animals↗
PubMed1983

Hemolytic complement measurement in eleven species of nonhuman primates.

A microtiter system was used to measure hemolytic complement levels in serum from eleven nonhuman primate species. The species studied were Macaca mulatta (rhesus macaque), Macaca radiata (bonnet macaque), Macaca nemestrina (pig-tailed macaque), Macaca fascicularis (crab-eating macaque), Macaca speciosa (stumptailed macaque), Papio cynocephalus (yellow baboon), Papio anubis (olive baboon), Cercopithecus aethiops (African green monkey), Aotus trivirgatus (owl monkey), Ateles fusceps robustus (spider monkey), and Galago crassicaudatus panganiensis (thick-tailed galago). The optimal hemolytic complement titer of the various nonhuman primate species was found to vary with different species sources of erythrocytes and anti-erythrocyte reagents used in the assay. No single erythrocyte and anti-erythrocyte test reagent produced optimal titers for all of the primate species examined. Sera from several species was found to have high spontaneous lytic activity towards non-sensitized sheep erythrocytes which for six species (M. mulatta, M. radiata, M. speciosa, P. cynocephalus, P. anubis and A. trivirgatus) was equal to the titer for antibody sensitized erythrocytes. Evidence of alternate pathway complement activation as a possible reason for the high titer of lytic activity towards unsensitized erythrocytes could not be demonstrated for any nonhuman primate species. In one species, M. mulatta, the sensitizing activity of normal serum for sheep erythrocytes was shown to be in the IgM containing fraction obtained with gel filtration and to be absorbed by boiled sheep erythrocyte stroma which contains Forssman antigen.

Animals↗