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Nonhuman Primates (nonhuman + primate)
Terms modified by Nonhuman Primates Selected AbstractsPotent and Selective Inhibition of Human Cathepsin K Leads to Inhibition of Bone Resorption In Vivo in a Nonhuman PrimateJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2001George B. Stroup Abstract Cathepsin K is a cysteine protease that plays an essential role in osteoclast-mediated degradation of the organic matrix of bone. Knockout of the enzyme in mice, as well as lack of functional enzyme in the human condition pycnodysostosis, results in osteopetrosis. These results suggests that inhibition of the human enzyme may provide protection from bone loss in states of elevated bone turnover, such as postmenopausal osteoporosis. To test this theory, we have produced a small molecule inhibitor of human cathepsin K, SB-357114, that potently and selectively inhibits this enzyme (Ki = 0.16 nM). This compound potently inhibited cathepsin activity in situ, in human osteoclasts (inhibitor concentration [IC]50 = 70 nM) as well as bone resorption mediated by human osteoclasts in vitro (IC50 = 29 nM). Using SB-357114, we evaluated the effect of inhibition of cathepsin K on bone resorption in vivo using a nonhuman primate model of postmenopausal bone loss in which the active form of cathepsin K is identical to the human orthologue. A gonadotropin-releasing hormone agonist (GnRHa) was used to render cynomolgus monkeys estrogen deficient, which led to an increase in bone turnover. Treatment with SB-357114 (12 mg/kg subcutaneously) resulted in a significant reduction in serum markers of bone resorption relative to untreated controls. The effect was observed 1.5 h after the first dose and was maintained for 24 h. After 5 days of dosing, the reductions in N-terminal telopeptides (NTx) and C-terminal telopeptides (CTx) of type I collagen were 61% and 67%, respectively. A decrease in serum osteocalcin of 22% was also observed. These data show that inhibition of cathepsin K results in a significant reduction of bone resorption in vivo and provide further evidence that this may be a viable approach to the treatment of postmenopausal osteoporosis. [source] Recent Discoveries on the Control of Gonadotrophin-Releasing Hormone Neurones in Nonhuman PrimatesJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2010E. Terasawa Since Ernst Knobil proposed the concept of the gonadotrophin-releasing hormone (GnRH) pulse-generator in the monkey hypothalamus three decades ago, we have made significant progress in this research area with cellular and molecular approaches. First, an increase in pulsatile GnRH release triggers the onset of puberty. However, the question of what triggers the pubertal increase in GnRH is still unclear. GnRH neurones are already mature before puberty but GnRH release is suppressed by a tonic GABA inhibition. Our recent work indicates that blocking endogenous GABA inhibition with the GABAA receptor blocker, bicuculline, dramatically increases kisspeptin release, which plays an important role in the pubertal increase in GnRH release. Thus, an interplay between the GABA, kisspeptin, and GnRH neuronal systems appears to trigger puberty. Second, cultured GnRH neurones derived from the olfactory placode of monkey embryos exhibit synchronised intracellular calcium, [Ca2+]i, oscillations and release GnRH in pulses at approximately 60-min intervals after 14 days in vitro (div). During the first 14 div, GnRH neurones undergo maturational changes from no [Ca2+]i oscillations and little GnRH release to the fully functional state. Recent work also shows GnRH mRNA expression increases during in vitro maturation. This mRNA increase coincides with significant demethylation of a CpG island in the GnRH 5,-promoter region. This suggests that epigenetic differentiation occurs during GnRH neuronal maturation. Third, oestradiol causes rapid, direct, excitatory action in GnRH neurones and this action of oestradiol appears to be mediated through a membrane receptor, such as G-protein coupled receptor 30. [source] The Effects of Ethanol Consumption on Vasculogenesis Potential in Nonhuman PrimatesALCOHOLISM, Issue 1 2008J. Koudy Williams Background:, Vasculogenesis is essential to the preservation and repair of damaged or diseased vessels. Alcohol is the most commonly abused drug among young adults, but its effects on vessel growth and repair are unknown. The basis of vascular repair is endothelial progenitor cell (EPC) recruitment to assist in the formation of new vascular network (vasculogenesis). Therefore, the objective of this study was to measure the effects of ethanol consumption on the production, mobilization and vasculogenesis potential EPCs in nonhuman primates. Methods:, Four to five year-old (young adult) male rhesus monkeys consumed monkey chow and water (Control, n = 7), or chow and water + ethanol (Alcohol, 2.45 g/d, n = 7) for 12 months. Peripheral blood (PB) and bone marrow (BM) samples were collected for fluorescence-activated cell-sorting analysis of cell surface antigens (CD45, CD31, CD44, CD133, VEGF-R2 , or KDR); and for capillary formation on Matrigel-coated plates. Results:, There were greater numbers of nonhematopoeitic stromal cells (CD45,) and putative mesenchymal progenitor cells (CD45,/CD44+) in the PB and BM of Alcohol versus Control monkeys (p < 0.05). Additionally, there were greater numbers of EPCs (CD45,/CD133+/KDR+) in the BM and PB of Alcohol versus Control monkeys (p < 0.05). However, the EPCs of Alcohol monkeys were less likely to form capillaries on matrigel-coated plates than Control monkeys (p < 0.05). Conclusions:, Ethanol consumption in monkeys markedly increased the production and mobilization of EPCs, but decreased their ability to form capillaries. The pathophysiologic consequences of such effects are unclear, but may represent an ethanol-induced chronic stress on the BM, resulting in EPC. [source] Portal Venous Donor-Specific Transfusion in Conjunction with Sirolimus Prolongs Renal Allograft Survival in Nonhuman PrimatesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009K. K. Dhanireddy Pretransplant exposure to donor antigen is known to modulate recipient alloimmunity, and frequently results in sensitization. However, donor-specific transfusion (DST) can have a protolerant effect that is dependent on route, dose and coadministered immunosuppression. Rodent studies have shown in some strain combinations that portal venous (PV) DST alone can induce tolerance, and uncontrolled clinical use of PVDST has been reported. In order to determine if pretransplant PVDST has a clinically relevant salutary effect, we studied it and the influence of concomitant immunosuppression in rhesus monkeys undergoing renal allotransplantation. Animals received PVDST with unfractionated bone marrow and/or tacrolimus or sirolimus 1 week prior to transplantation. Graft survival was assessed without any posttransplant immunosuppression. PVDST alone or in combination with tacrolimus was ineffective. However, PVDST in combination with sirolimus significantly prolonged renal allograft survival to a mean of 24 days. Preoperative sirolimus alone had no effect, and peripheral DST with sirolimus prolonged graft survival in 2/4 animals, but resulted in accelerated rejection in 2/4 animals. These data demonstrate that PVDST in combination with sirolimus delays rejection in a modest but measurable way in a rigorous model. It may thus be a preferable method for donor antigen administration. [source] Engraftment of Adult Porcine Islet Xenografts in Diabetic Nonhuman Primates Through Targeting of Costimulation PathwaysAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2007K. Cardona Recent advances in human allogeneic islet transplantation have established ,-cell replacement therapy as a potentially viable treatment option for individuals afflicted with Type 1 diabetes. Two recent successes, one involving neonatal porcine islet xenografts transplanted into diabetic rhesus macaques treated with a costimulation blockade-based regimen and the other involving diabetic cynomolgus monkeys transplanted with adult porcine islet xenografts treated with an alternative multidrug immunosuppressive regimen have demonstrated the feasibility of porcine islet xenotransplantation in nonhuman primate models. In the current study, we assessed whether transplantation of adult porcine islet xenografts into pancreatectomized macaques, under the cover of a costimulation blockade-based immunosuppressive regimen (CD28 and CD154 blockade), could correct hyperglycemia. Our findings suggest that the adult porcine islets transplanted into rhesus macaques receiving a costimulation blockade-based regimen are not uniformly subject to hyperacute rejection, can engraft (2/5 recipients), and have the potential to provide sustained normoglycemia. These results provide further evidence to suggest that porcine islet xenotransplantation may be an attainable strategy to alleviate the islet supply crisis that is one of the principal obstacles to large-scale application of islet replacement therapy in the treatment of Type 1 diabetes. [source] Categorical Perception and Conceptual Judgments by Nonhuman Primates: The Paleological Monkey and the Analogical ApeCOGNITIVE SCIENCE - A MULTIDISCIPLINARY JOURNAL, Issue 3 2000Roger K. R. Thompson Studies of the conceptual abilities of nonhuman primates demonstrate the substantial range of these abilities as well as their limitations. Such abilities range from categorization on the basis of shared physical attributes, associative relations and functions to abstract concepts as reflected in analogical reasoning about relations between relations. The pattern of results from these studies point to a fundamental distinction between monkeys and apes in both their implicit and explicit conceptual capacities. Monkeys, but not apes, might be best regarded as "paleo-logicans" in the sense that they form common class concepts of identity on the basis of identical predicates (i.e., shared features). The discrimination of presumably more abstract relations commonly involves relatively simple procedural strategies mediated by associative processes likely shared by all mammals. There is no evidence that monkeys can perceive, let alone judge, relations-between-relations. This analogical conceptual capacity is found only in chimpanzees and humans. Interestingly, the "analogical ape," like the child, can make its analogical knowledge explicit only if it is first provided with a symbol system by which propositional representations can be encoded and manipulated. [source] Genetic influences on behavioral inhibition and anxiety in juvenile rhesus macaquesGENES, BRAIN AND BEHAVIOR, Issue 4 2008J. Rogers In humans and other animals, behavioral responses to threatening stimuli are an important component of temperament. Among children, extreme behavioral inhibition elicited by novel situations or strangers predicts the subsequent development of anxiety disorders and depression. Genetic differences among children are known to affect risk of developing behavioral inhibition and anxiety, but a more detailed understanding of genetic influences on susceptibility is needed. Nonhuman primates provide valuable models for studying the mechanisms underlying human behavior. Individual differences in threat-induced behavioral inhibition (freezing behavior) in young rhesus monkeys are stable over time and reflect individual levels of anxiety. This study used the well-established human intruder paradigm to elicit threat-induced freezing behavior and other behavioral responses in 285 young pedigreed rhesus monkeys. We examined the overall influence of quantitative genetic variation and tested the specific effect of the serotonin transporter promoter repeat polymorphism. Quantitative genetic analyses indicated that the residual heritability of freezing duration (behavioral inhibition) is h2 = 0.384 (P = 0.012) and of ,orienting to the intruder' (vigilance) is h2 = 0.908 (P = 0.00001). Duration of locomotion and hostility and frequency of cooing were not significantly heritable. The serotonin transporter polymorphism showed no significant effect on either freezing or orienting to the intruder. Our results suggest that this species could be used for detailed studies of genetic mechanisms influencing extreme behavioral inhibition, including the identification of specific genes that are involved in predisposing individuals to such behavior. [source] Spontaneous pancreatic islet amyloidosis in 40 baboonsJOURNAL OF MEDICAL PRIMATOLOGY, Issue 2 2002G.B. Hubbard Spontaneous amyloidosis occurs in many nonhuman primate species but remains difficult to diagnose and treat. Nonhuman primates continue to offer promise as animal models in which to study amyloidosis in humans. Amyloidosis was not diagnosed clinically but was found histologically in four male and 36 female baboons. The baboons averaged 18 years of age at death (range, 7,28 years). Clinical signs, if present, were hyperglycemia and cachexia. Blood glucose values were elevated in 12 of 30 baboons with available clinical pathology data. Four baboons had been clinically diagnosed as diabetic and three were treated with insulin. Amyloid was found in the islets of Langerhans of the pancreas in 40 baboons; 35 baboons had amyloid only in the islets of Langerhans. Amyloid was found in nonislet tissue of baboons as follows: five, nonislet pancreas; four, intestine and adrenal; three, kidney; two, prostate and spleen; and one each, lymph node, liver, gall bladder, stomach, tongue, urinary bladder, and salivary gland. Sections of paraffin-embedded tissues were evaluated for amyloid with hematoxylin and eosin (HE) and congo red (CR) staining, and using immunohistochemistry for human islet amyloid polypeptide (IAPP), calcitonin gene-related peptide (CGRP), glucagon, pancreatic polypeptide (PP), somatostatin (SS), and porcine insulin. Islet amyloid was positive with HE in 40 baboons, with CR in 39 baboons, and with IAPP and CGRP in 35 baboons. IAPP and CGRP only stained islet amyloid. PP, SS, glucagon, and porcine insulin did not stain amyloid. Islet amyloidosis in the baboon appears to be difficult to diagnose clinically, age-related, and similar to islet amyloidosis in other species. The baboon may be a good model for the study of islet amyloidosis in humans. [source] Apparent density of the primate calcaneo-cuboid joint and its association with locomotor mode, foot posture, and the "midtarsal break"AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 2 2010Matthew G. Nowak Abstract Primates use a range of locomotor modes during which they incorporate various foot postures. Humans are unique compared with other primates in that humans lack a mobile fore- and midfoot. Rigidity in the human foot is often attributed to increased propulsive and stability requirements during bipedalism. Conversely, fore- and midfoot mobility in nonhuman primates facilitates locomotion in arboreal settings. Here, we evaluated apparent density (AD) in the subchondral bone of human, ape, and monkey calcanei exhibiting different types of foot loading. We used computed tomography osteoabsorptiometry and maximum intensity projection (MIP) maps to visualize AD in subchondral bone at the cuboid articular surface of calcanei. MIPs represent 3D volumes (of subchondral bone) condensed into 2D images by extracting AD maxima from columns of voxels comprising the volumes. False-color maps are assigned to MIPs by binning pixels in the 2D images according to brightness values. We compared quantities and distributions of AD pixels in the highest bin to test predictions relating AD patterns to habitual locomotor modes and foot posture categories of humans and several nonhuman primates. Nonhuman primates exhibit dorsally positioned high AD concentrations, where maximum compressive loading between the calcaneus and cuboid likely occurs during "midtarsal break" of support. Humans exhibit less widespread areas of high AD, which could reflect reduced fore- and midfoot mobility. Analysis of the internal morphology of the tarsus, such as subchondral bone AD, potentially offers new insights for evaluating primate foot function during locomotion. Am J Phys Anthropol, 2010. © 2009 Wiley-Liss, Inc. [source] Perceptions of nonhuman primates in human,wildlife conflict scenariosAMERICAN JOURNAL OF PRIMATOLOGY, Issue 10 2010Catherine M. Hill Abstract Nonhuman primates (referred to as primates in this study) are sometimes revered as gods, abhorred as evil spirits, killed for food because they damage crops, or butchered for sport. Primates' perceived similarity to humans places them in an anomalous position. While some human groups accept the idea that primates "straddle" the human,nonhuman boundary, for others this resemblance is a violation of the human,animal divide. In this study we use two case studies to explore how people's perceptions of primates are often influenced by these animals' apparent similarity to humans, creating expectations, founded within a "human morality" about how primates should interact with people. When animals transgress these social rules, they are measured against the same moral framework as humans. This has implications for how people view and respond to certain kinds of primate behaviors, their willingness to tolerate co-existence with primates and their likely support for primate conservation initiatives. Am. J. Primatol. 72:919,924, 2010. © 2010 Wiley-Liss, Inc. [source] The unique value of primate models in translational researchAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009Carol A. Shively Abstract This special issue of AJP is focused on research using nonhuman primates as models to further the understanding of women's health. Nonhuman primates play a unique role in translational science by bridging the gap between basic and clinical investigations. The use of nonhuman primates in biomedical research challenges our resolve to treat all life as sacred. The scientific community has responded by developing ethical guidelines for the care and the use of primates and clarifying the responsibility of investigators to insure the physical and psychological well-being of nonhuman primates used in research. Preclinical investigations often involve the use of animal models. Rodent models have been the mainstay of biomedical science and have provided enormous insight into the workings of many mammalian systems that h ave proved applicable to human biological systems. Rodent models are dissimilar to primates in numerous ways, which may limit the generalizability to human biological systems. These limitations are much less likely in nonhuman primates and in Old World primates, in particular, Macaques are useful models for investigations involving the reproductive system, bioenergetics, obesity and diabetes, cardiovascular health, central nervous system function, cognitive and social behavior, the musculoskeletal system, and diseases of aging. This issue considers primate models of polycystic ovary syndrome; diet effects on glycemic control, breast and endometrium; estrogen, reproductive life stage and atherosclerosis; estrogen and diet effects on inflammation in atherogenesis; the neuroprotective effects of estrogen therapy; social stress and visceral obesity; and sex differences in the role of social status in atherogenesis. Unmet research needs in women's health include the use of diets in nonhuman primate studies that are similar to those consumed by human beings, primate models of natural menopause, dementia, hypertension, colon cancer, and frailty in old age, and dedicated colonies for the study of breast cancer. Am. J. Primatol. 71:715,721, 2009. © 2009 Wiley-Liss, Inc. [source] Use of primates in research: A global overviewAMERICAN JOURNAL OF PRIMATOLOGY, Issue 4 2004Hans-Erik Carlsson Abstract We assessed the use of nonhuman primates and nonhuman primate biological material in research by reviewing studies published in 2001 in peer-reviewed journals. The number and species of primates used, the origin of the animals, the type of study, the area of research of the investigation, and the location at which the research was performed were tabulated. Additionally, factors related to the animals that may have affected the outcome of the experiments were recorded. A total of 2,937 articles involving 4,411 studies that employed nonhuman primates or nonhuman primate biological material were identified and analyzed. More than 41,000 animals were represented in the studies published in 2001. In the 14% of studies for which re-use could be determined, 69% involved animals that had been used in previous experiments. Published studies most commonly used nonhuman primates or nonhuman primate biological material from the species Chlorocebus aethiops (19%), Macaca mulatta (18%), M. fascicularis (9%), and Papio spp. (6%). Of these studies, 54% were classified as in vitro studies, 14% as noninvasive, 30% as chronic, and 1% were considered acute. Nonhuman primates were primarily used in research areas in which they appear to be the most appropriate models for humans. The most common areas of research were microbiology (including HIV/AIDS (26%)), neuroscience (19%), and biochemistry/chemistry (12%). Most (84%) of the primate research published in 2001 was conducted in North America, Europe, and Japan. The animals and conditions under which they were housed and used were rarely described. Although it is estimated that nonhuman primates account for an extremely small fraction of all animals used in research, their special status makes it important to report the many husbandry and environmental factors that influence the research results generated. This analysis has identified that editors rarely require authors to provide comprehensive information concerning the subjects (e.g., their origin), treatment conditions, and experimental procedures utilized in the studies they publish. The present analysis addresses the use of primates for research, including the effects of a shortage of suitable nonhuman primate subjects in many research areas. Am. J. Primatol. 63:225,237, 2004. © 2004 Wiley-Liss, Inc. [source] Primate Numerical Competence: Contributions Toward Understanding Nonhuman CognitionCOGNITIVE SCIENCE - A MULTIDISCIPLINARY JOURNAL, Issue 3 2000Sarah T. Boysen Nonhuman primates represent the most significant extant species for comparative studies of cognition, including such complex phenomena as numerical competence, among others. Studies of numerical skills in monkeys and apes have a long, though somewhat sparse history, although questions for current empirical studies remain of great interest to several fields, including comparative, developmental, and cognitive psychology; anthropology; ethology; and philosophy, to name a few. In addition to demonstrated similarities in complex information processing, empirical studies of a variety of potential cognitive limitations or constraints have provided insights into similarities and differences across the primate order, and continue to offer theoretical and pragmatic directions for future research. An historical overview of primate numerical studies is presented, as well as a summary of the 17-year research history, including recent findings, of the Comparative Cognition Project at The Ohio State University Chimpanzee Center. Overall, the archival literature on number-related skills and counting in nonhuman primates offers important implications for revising our thinking about comparative neuroanatomy, cross-species (human/ape) cognitive similarities and differences, and the evolution of cognition represented by the primate continuum. [source] Systems biology approaches for toxicology,JOURNAL OF APPLIED TOXICOLOGY, Issue 3 2007William Slikker Jr Abstract Systems biology/toxicology involves the iterative and integrative study of perturbations by chemicals and other stressors of gene and protein expression that are linked firmly to toxicological outcome. In this review, the value of systems biology to enhance the understanding of complex biological processes such as neurodegeneration in the developing brain is explored. Exposure of the developing mammal to NMDA (N -methyl- d -aspartate) receptor antagonists perturbs the endogenous NMDA receptor system and results in enhanced neuronal cell death. It is proposed that continuous blockade of NMDA receptors in the developing brain by NMDA antagonists such as ketamine (a dissociative anesthetic) causes a compensatory up-regulation of NMDA receptors, which makes the neurons bearing these receptors subsequently more vulnerable (e.g. after ketamine washout), to the excitotoxic effects of endogenous glutamate: the up-regulation of NMDA receptors allows for the accumulation of toxic levels of intracellular Ca2+ under normal physiological conditions. Systems biology, as applied to toxicology, provides a framework in which information can be arranged in the form of a biological model. In our ketamine model, for example, blockade of NMDA receptor up-regulation by the co-administration of antisense oligonucleotides that specifically target NMDA receptor NR1 subunit mRNA, dramatically diminishes ketamine-induced cell death. Preliminary gene expression data support the role of apoptosis as a mode of action of ketamine-induced neurotoxicity. In addition, ketamine-induced cell death is also prevented by the inhibition of NF- ,B translocation into the nucleus. This process is known to respond to changes in the redox state of the cytoplasm and has been shown to respond to NMDA-induced cellular stress. Although comprehensive gene expression/proteomic studies and mathematical modeling remain to be carried out, biological models have been established in an iterative manner to allow for the confirmation of biological pathways underlying NMDA antagonist-induced cell death in the developing nonhuman primate and rodent. Published in 2007 John Wiley & Sons, Ltd. [source] Molecular cloning of three nonhuman primate follicle stimulating hormone ,-subunit cDNAsJOURNAL OF MEDICAL PRIMATOLOGY, Issue 6 2001M.J. Wolfgang The follicle stimulating hormone (FSH) ,-subunit cDNAs were cloned and sequenced for an old world primate, the rhesus monkey (Macaca mulatta), and two New World primates, the common marmoset (Callithrix jacchus) and pygmy marmoset (Cebuella pygmaea). The cDNA and predicted amino acid sequences of the rhesus monkey FSH ,-subunit were related most closely to the human FSH , -subunit (>96% identity). The common and pygmy marmosets have identical FSH , -subunit cDNAs, whereas the marmoset FSH , -subunit diverges from the rhesus and human molecules with less than 93% identity. These results have significance for the implementation of assisted reproductive technologies in the nonhuman primate as well as the evolution of genes encoding reproductive hormones. [source] Genetic and Other Contributions to Alcohol Intake in Rhesus Macaques (Macaca mulatta)ALCOHOLISM, Issue 3 2006Joseph G. Lorenz Background: The etiology of alcoholism and alcohol abuse, like many other complex diseases, is heterogeneous and multifactorial. Numerous studies demonstrate a genetic contribution to variation in the expression of alcohol-related disorders in humans. Over the past decade, nonhuman primates have emerged as a valuable model for some aspects of human alcohol abuse because of their phylogenetic proximity to humans. Long-term, longitudinal studies of rhesus macaques (Macaca mulatta) have provided much insight into environmental influences, especially early life experiences, on alcohol consumption and behavior patterns that characterize alcohol intake later in life. It is not known, however, whether there is a genetic component as well to the variation seen in alcohol consumption in rhesus macaques. A significant genetic component to variation in alcohol consumption in rhesus macaques would show for the first time that like humans, for nonhuman primates additive genetic influences are important. Moreover, their use as a model for alcohol-related disorders in humans would have even greater relevance and utility for designing experiments incorporating the expanding molecular genetics field, and allow researchers to investigate the interaction among the known environmental influences and various genotypes. Methods: In this study, we investigate factors contributing to variation in alcohol consumption of 156 rhesus macaques collected over 10 years when subjects were adolescent in age, belonging to a single extended pedigree, with each cohort receiving identical early rearing backgrounds and subsequent treatments. To measure alcohol consumption each animal was provided unfettered simultaneous access both to an aspartame-sweetened 8.4% (v/v) alcohol-water solution, the aspartame-sweetened vehicle, and to water for 1 hour each day during the early afternoon between 13:00 and 15:00 in their home cages for a period of 5 to 7 weeks. We use multiple regression to identify factors that significantly affect alcohol consumption among these animals and a maximum likelihood program (ASReml) that, controlling for the significant factors, estimates the genetic contribution to the variance in alcohol consumption. Results: Multiple regression analysis identified test cohort and rearing environment as contributing to 57 and 2%, respectively, of the total variance in alcohol consumption. Of the remaining 41% of the variance about half (19.8%) was attributable to additive genetic effects using a maximum likelihood program. Conclusion: This study demonstrates that, as in humans, there are additive genetic factors that contribute to variation in alcohol consumption in rhesus macaques, with other nongenetic factors accounting for substantial portions of the variance in alcohol consumption, Our findings show the presence of an additive genetic component and suggest the potential utility of the nonhuman primate as a molecular genetics tool for understanding alcohol abuse and alcoholism. [source] Field primatology of today: current ethical issuesAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2010K.C. MacKinnon Abstract As members of professional organizations such as American Society of Primatologists (ASP) and the International Primatological Society (IPS), primatologists must adhere to a set of nonhuman primate-focused principles outlined in resolutions and policy statements on, for example, the ethical treatment of nonhuman primates. Those of us that work in the field must also address issues such as the protection of primate health in the wild and the conservation of wild primate populations. Moreover, we increasingly find ourselves in complex situations where we must balance human and nonhuman primate needs and interests. The selection of commentary pieces in this edition of the American Journal of Primatology originated from presentations given in the symposium, Field Primatology of Today: Navigating the Ethical Landscape, held at the 32nd Annual Meeting of the American Society of Primatologists (ASP) in September 2009. The goals of that symposium and these resulting commentary pieces are threefold: (1) to revive a discussion of key contemporary ethical issues faced by field primatologists, (2) to highlight the need for centrally placed ethical considerations in various facets of our professional lives, particularly research and teaching, and (3) to consider what a comprehensive ethical code that addresses all of these issues might look like. Am. J. Primatol. 72:749,753, 2010. © 2010 Wiley-Liss, Inc. [source] Baboon vaginal microbiota: an overlooked aspect of primate physiologyAMERICAN JOURNAL OF PRIMATOLOGY, Issue 6 2010Angel J. Rivera Abstract The bacterial population of the primate vaginal canal is an infant primate's first exposure to the microbial population inhabiting the outside world. Yet, little is known about this population and the effect it might have on the development and survival of the infant primate. As a first step toward characterizing the vaginal microbiota of a nonhuman primate, we used denaturing gradient gel electrophoresis to evaluate variations in the vaginal microbiota of a group of 35 baboons (Papio hamadryas), which were housed in a facility where they shared the same diet and the same environmental conditions. We found that, despite the uniform environment, there were appreciable differences in the composition of the microbiota from one individual to another. Our results also indicate that a simple swab test is sufficient for sampling the vaginal microbiota in the field, a finding that should help make more detailed characterization of the microbiota of wild primates feasible in the future. Am. J. Primatol. 72:467,474, 2010. © 2010 Wiley-Liss, Inc. [source] Skeletal health: primate model of postmenopausal osteoporosisAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009S.Y. Smith Abstract Currently, the nonhuman primate is the most widely used large animal model to evaluate the safety and efficacy of new drug entities to treat or prevent estrogen-deficiency-induced bone loss and osteoporosis. Surgical ovariectomy (OVX) induces a state of high bone turnover and rapid bone loss establishing a new steady-state bone mass within 8,9 months. Many systems in the monkey are similar to humans, including skeletal and reproductive physiology and the immune system, making this a plausible model suitable to evaluate the effects of new bone drugs. The long-term sequelae following OVX and withdrawal of monthly exposure to cyclic reproductive hormones in older female monkeys (cynomolgus and rhesus) mimics estrogen depletion and postmenopausal bone loss occurring in women. Characterization of the primate model revealed an apparent limitation to the extent of bone loss. Animals lose bone mass after OVX, but the extent of the bone loss cannot be described as osteoporotic. The small differences between OVX and sham-operated controls in many important bone measurements is overcome by including 15,20 animals per group to provide adequate statistical power. The long-term, at least 16 month, bone safety studies performed to satisfy regulatory guidelines provide an opportunity to study treatment effects for an extended period not covered in shorter-term safety studies. In vivo end-points such as densitometry and biochemical markers translate easily to clinical use, while biomechanical end-points that cannot be measured clinically can be used to predict fracture prevention. To date, the monkey OVX model has been used to support submissions for many new drugs including anabolics, bisphosphonates and selective estrogen receptor modulators. Despite its limitations, the OVX monkey model remains the best characterized of the large animal models of osteopenia and has become integral to osteoporosis drug development. Am. J. Primatol. 71:752,765, 2009. © 2009 Wiley-Liss, Inc. [source] Considering human,primate transmission of measles virus through the prism of risk analysisAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2006Lisa Jones-Engel Abstract Measles is a respiratory virus that is endemic to humans. Human,nonhuman primate (NHP) transmission of the measles virus has been shown to cause significant morbidity and mortality in NHP populations. We investigated serological evidence of exposure to measles virus in two free-ranging populations of macaques at the Bukit Timah (BTNR) and Central Catchment Nature (CCNR) reserves in Singapore and the Swoyambhu Temple in Katmandu, Nepal. At BTNR/CCNR none of the 38 macaques (Macaca fascicularis) sampled were seropositive for antibodies to measles virus. In contrast, at Swoyambhu 100% (n=39) of the macaques (M. mulatta) sampled were seropositive for antibodies to the measles virus. Here the contrasting seroprevalences of the two sites are analyzed using risk analysis. These case studies show how risk analysis can be used to approach the phenomenon of cross-species pathogen transmission. Am. J. Primatol. 68:868,879, 2006. © 2006 Wiley-Liss, Inc. [source] Acute and Chronic Vascular Rejection in Nonhuman Primate Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2006G. Wieczorek A nonhuman primate (NHP) study was designed to evaluate in nonlife-supporting kidney allografts the progression from acute rejection with transplant endarteritis (TXA) to chronic rejection (CR) with sclerosing vasculopathy. Group G1 (n = 6) received high cyclosporine A (CsA) immunosuppression and showed neither TXA nor CR during 90 days post-transplantation. Group G2 (n = 6) received suboptimal CsA immunosuppression and showed severe TXA with graft loss within 46 days (median). Arterial intimal changes included infiltration of macrophages and T lymphocytes (CD3, CD4, CD8) with few myofibroblasts, abundant fibronectin/collagen IV, scant collagens I/III, high rate of cellular proliferation and no C4d accumulation along peritubular capillaries. Group G3 (n = 12) received suboptimal CsA and anti-rejection therapy (rabbit ATG + methylprednisolone + CsA) of TXA. Animals developed CR and lost grafts within 65 days (median). As compared to G2, the arterial intimal changes showed less macrophages and T lymphocytes, an increased number of myofibroblasts, abundant fibronectin/collagen IV and scar collagens I/III, C4d deposition along capillaries in 60% of animals and transplant glomerulopathy in 80% of animals. In conclusion, CR is an immune stimulated process initiated during TXA with the accumulation and proliferation of myofibroblasts, and progressive deposition of collagens in the intima. Our experimental design appears well suited to study events leading to CR. [source] Prolonged Survival of Allogeneic Islets in Cynomolgus Monkeys After Short-Term Anti-CD154-Based Therapy: Nonimmunologic Graft Failure?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2006M. Koulmanda Conventional drug therapy and several anti-CD154 mAb-based regimens were tested in the nonhuman primate (NHP) islet allograft model and found to be inadequate because islets were lost to rejection. Short-term therapy with an optimized donor-specific transfusion (DST) + rapamycin (RPM) + anti-CD154 mAb regimen enables immunosuppression drug-free islet allograft function for months following cessation of therapy in the NHP islet allograft model. After a substantial period of drug-free graft function, these allografts slowly and progressively lost function. Pathologic studies failed to identify islet allograft rejection as a destructive islet invasive lymphocytic infiltration of the allograft was not detected. To evaluate the mechanism, immunologic versus nonimmunologic, of the late islet allograft loss in hosts receiving the optimized therapeutic regimen, we performed experiments with islet autografts and studied islet function in NHPs with partial pancreatectomy. The results in both experiments utilizing autologous islet allografts and partially pancreatectomized hosts reinforce the view that the presence of a marginal islet mass leads to slowly progressive nonimmunological islet loss. Long-term clinically successful islet cell transplantation cannot be realized in the absence of parallel improvements in tolerizing regimens and in the preparation of adequate numbers of islets. [source] Learning large-scale spatial relationships in a maze and effects of MK-801 on retrieval in the rhesus monkeyDEVELOPMENTAL NEUROBIOLOGY, Issue 13 2007Jian Hong Wang Abstract Monkeys have strong abilities to remember the visual properties of potential food sources for survival in the nature. The present study demonstrated the first observations of rhesus monkeys learning to solve complex spatial mazes in which routes were guided by visual cues. Three monkeys were trained in a maze (6 m × 6 m) included of four different mazes. We recorded the cue and cup errors, latencies, and pathway for each trial. The data showed that monkeys learned the target place after three days in the first maze and spent a shorter time in learning the following mazes. The maze was an efficient method to measure the ability and proceeding of spatial memory in monkeys. Moreover, working memory can also be tested by using the maze. MK-801 at 0.02 mg/kg but not at 0.005 mg/kg impaired monkeys' retrieval of spatial memory after they learned all four mazes. The present maze may provide an efficient method to help bridging the gap in cognition between nonhuman primates and humans, and in particular to gain insight into human cognitive function and dysfunction. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] Social withdrawal behaviors in nonhuman primates and changes in neuroendocrine and monoamine concentrations during a separation paradigm,DEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2005Kristine Erickson Abstract This study investigated relationships between withdrawal behaviors in rhesus macaques and changes in monoamine metabolite and endocrine concentrations during repeated psychosocial stress. Rhesus monkeys (N,=,71) experienced maternal separation in which four separations took place during four consecutive weeks. Behavioral observations were made, as well as plasma concentrations of cortisol and cerebrospinal fluid concentrations of the serotonin, dopamine, and norepinephrine metabolites were obtained. Animals were assigned to high, moderate, and low withdrawal groups, defined using baseline durations of withdrawal behaviors. Highly withdrawn animals showed less reduction than nonwithdrawn animals in serotonin metabolite concentrations over repeated separations. Highly withdrawn macaques also failed to significantly reduce cortisol concentrations across separation weeks. More adaptation in central serotonin functioning and cortisol concentrations was seen in nonwithdrawn primates than in highly withdrawn primates; these findings have implications for increased risk of developing anxiety disorders in highly inhibited children. © 2005 Wiley Periodicals, Inc. Dev Psychobiol 46:331,339, 2005. [source] Localized transmeningeal muscimol prevents neocortical seizures in rats and nonhuman primates: Therapeutic implicationsEPILEPSIA, Issue 4 2009Nandor Ludvig Summary Purpose:, To determine whether muscimol delivered epidurally or into the subarachnoid space can prevent and/or terminate acetylcholine (Ach),induced focal neocortical seizures at concentrations not affecting behavior and background electroencephalography (EEG) activity. Methods:, Rats (n = 12) and squirrel monkeys (n = 3) were chronically implanted with an epidural or subarachnoid drug delivery device, respectively, over the right frontal/parietal cortex, with adjacent EEG electrodes. Recordings were performed in behaving rats and chaired monkeys. Via the implants, either a control solution (artificial cerebrospinal fluid, ACSF) or muscimol (0.25,12.5 mm) was delivered locally as a "pretreatment," followed by the similar delivery of a seizure-inducing concentration of Ach. In five additional rats, the quantities of food-pellets consumed during epidural ACSF and muscimol (2.5 mm) exposures were measured. In a last group of four rats, muscimol (0.8,2.5 mm) was delivered epidurally during the ongoing, Ach-induced EEG seizure. Results:, In contrast to ACSF pretreatments, epidural muscimol pretreatment in rats completely prevented the seizures at and above 2.5 mm. In the monkeys, subarachnoid muscimol pretreatments at 2.5 mm completely prevented the focal-seizure,inducing effect of Ach, whereas similar deliveries of ACSF did not affect the seizures. Furthermore, 2.5 mm epidural muscimol left the eating behavior of rats intact and caused only slight changes in the EEG power spectra. Finally, muscimol delivery during Ach-induced EEG seizures terminated the seizure activity within 1,3 min. Conclusions:, The results of this study suggest that muscimol is a viable candidate for the transmeningeal pharmacotherapy of intractable focal epilepsy. [source] Do animals have culture?EVOLUTIONARY ANTHROPOLOGY, Issue 3 2003Kevin N. Laland Abstract Culture is probably not rare in animals, although hard experimental evidence is lacking. The strongest case for culture is found in the species most amenable to experimental manipulation, rather than in nonhuman primates. Human culture is much more likely to be cumulative than animal culture, but the reasons for this are not well established. At this point, there is no reason to assume that cumulative culture depends critically on teaching, imitation, language, or perspective-taking. Currently, animals are being judged according to stricter criteria than humans. [source] Reproductive biology of nonhuman primatesEVOLUTIONARY ANTHROPOLOGY, Issue S1 2002Article first published online: 7 JAN 200, Mike H. Jurke First page of article [source] What can developmental defects of enamel reveal about physiological stress in nonhuman primates?EVOLUTIONARY ANTHROPOLOGY, Issue 4 2001Debbie Guatelli-Steinberg First page of article [source] Efficient hepatocyte engraftment and long-term transgene expression after reversible portal embolization in nonhuman primates,HEPATOLOGY, Issue 3 2009Ibrahim Dagher The feasibility of ex vivo gene therapy as an alternative to liver transplantation for the treatment of liver metabolic diseases needs to be analyzed in large animal models. This approach requires appropriate gene transfer vectors and effective hepatocyte engraftment. Lentiviral vectors have the ability to transduce nondividing differentiated cells, such as hepatocytes, and portal vein occlusion increases hepatocyte engraftment. We investigated whether reversible portal vein embolization combined with ex vivo lentivirus-mediated gene transfer is an effective approach for successful hepatocyte engraftment in nonhuman primates and whether the transgene remains expressed in the long term in transplanted hepatocytes in situ. Simian hepatocytes were isolated after left lobe resection, and the left and right anterior portal branches of animals were embolized with absorbable material. Isolated hepatocytes were labeled with Hoechst dye or transduced in suspension with lentiviruses expressing green fluorescent protein under the control of the human apolipoprotein A-II promoter and transplanted via the inferior mesenteric vein. The whole procedure was well tolerated. The embolized liver was revascularized within 2 weeks. The volume of nonembolized liver increased from 38.7% ± 0.8% before embolization to 55.9% ± 1% after embolization and hepatocytes significantly proliferated (10.5% ± 0.4% on day 3 after embolization). Liver repopulation after transplantation with Hoechst-labeled hepatocytes was 7.4% ± 1.2%. Liver repopulation was 2.1% ± 0.2% with transduced hepatocytes, a proportion similar to that obtained with Hoechst-labeled cells, given that the mean transduction efficacy of simian hepatocyte population was 34%. Transgene expression persisted at 16 weeks after transplantation. Conclusion: We have developed a new approach to improve hepatocyte engraftment and to express a transgene in the long term in nonhuman primates. This strategy could be suitable for clinical applications. (HEPATOLOGY 2009.) [source] Spatial memory and the monkey hippocampus: Not all space is created equalHIPPOCAMPUS, Issue 1 2009Pamela Banta Lavenex Abstract Studies of the role of the monkey hippocampus in spatial learning and memory, however few, have reliably produced inconsistent results. Whereas the role of the hippocampus in spatial learning and memory has been clearly established in rodents, studies in nonhuman primates have made a variety of claims that range from the involvement of the hippocampus in spatial memory only at relatively longer memory delays, to no role for the hippocampus in spatial memory at all. In contrast, we have shown that selective damage restricted to the hippocampus (CA regions) prevents the learning or use of allocentric, spatial relational representations of the environment in freely behaving adult monkeys tested in an open-field arena. In this commentary, we discuss a unifying framework that explains these apparently discrepant results regarding the role of the monkey hippocampus in spatial learning and memory. We describe clear and strict criteria to interpret the findings from previous studies and guide future investigations of spatial memory in monkeys. Specifically, we affirm that, as in the rodent, the primate hippocampus is critical for spatial relational learning and memory, and in a time-independent manner. We describe how claims to the contrary are the result of experimental designs that fail to recognize, and control for, egocentric (hippocampus-independent) and allocentric (hippocampus-dependent) spatial frames of reference. Finally, we conclude that the available data demonstrate unequivocally that the central role of the hippocampus in allocentric, spatial relational learning and memory is conserved among vertebrates, including nonhuman primates. © 2008 Wiley-Liss, Inc. [source] | |||||||||||||||||||