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Rhesus Macaques (rhesus + macaque)
Kinds of Rhesus Macaques Selected AbstractsChanges In Rhesus Macaque ,Coo' Vocalizations during Early DevelopmentETHOLOGY, Issue 10 2000Kurt Hammerschmidt In order to test whether ,coo' calls of young rhesus macaques, Macaca mulatta, undergo some modifications during early development, and to explore which factors may influence these changes, we studied the ontogeny of their contact call, the ,coo' call. Vocalizations were recorded during brief periods of social separation. Infants were either raised with their mothers and other conspecifics, or separated from their mothers at birth and housed in a nursery with other infants. We recorded calls uttered in the separation context from 20 infants. We digitized the first 50 calls of a given series and subjected them to a Fourier transform. From each frequency,time spectrum, we extracted 65 acoustic parameters using a software program (LMA 5.9). We then used a cluster analysis to separate the ,coo' calls from other call types. With increasing age, the ,coos' dropped in pitch and became more even. The course of amplitude became more constant and the call duration increased slightly. Nevertheless, we found a high intra-individual variation throughout the 5 mo. Neither rearing condition nor sex had any apparent influence on age-related changes in ,coo' structure. With one exception, all parameters that correlated with age could be explained by variation in weight. Therefore, we conclude that growth is the main factor accounting for the observed changes. [source] Alcohol Exposure Impairs Myeloid Dendritic Cell Function in Rhesus MacaquesALCOHOLISM, Issue 9 2009Robert W. Siggins Background:, Alcohol intoxication suppresses both the innate and adaptive immunities. Dendritic cells (DCs) are the major cell type bridging the innate and acquired immune responses. At the present time, the effects of alcohol on DC development in hematopoietic tissues and the functional activities of DCs are incompletely elucidated. This study investigated the impact of chronic alcohol exposure on the alteration of hematopoietic precursor cell and DC populations in the bone marrow and peripheral blood of rhesus macaques. Methods:, Rhesus macaques were administered alcohol or isocaloric sucrose daily for a period of 3 months through surgically implanted gastric catheters. Peripheral blood mononuclear cells (PBMCs) and bone marrow cells (BMCs) were isolated for flow cytometric analysis after 3 months. Monocytes were cultured with human IL-4 (10 ng/ml) and GM-CSF (50 ng/ml) in the absence and presence of alcohol (50 mM). On day 6 of the culture, a cocktail of stimulants including IL-1, (18 ng), IL-6 (1800 U), TNF-, (18 ng), and PGE2 (1.8 ,g) were added to the designated wells for transformation of immature dendritic cells (iDCs) to mature myeloid DCs. The cells were analyzed on day 8 by flow cytometry for expression of DC costimulatory molecule expression. Results:, EtOH-treated animals had significantly lower numbers of myeloid DCs (lineage-HLA-DR+CD11c+CD123,) in both the PBMCs and BMCs compared to controls (5,654 ± 1,273/106 vs. 2,353 ± 660/106 PBMCs and 503 ± 34 vs. 195 ± 44/106 BMCs). Under culture conditions, the number of lineage-HLA-DR+CD83+ cells was low in control wells (0.38 ± 0.08%). Alcohol inhibited the increase in the number of lineage-HLA-DR+CD83+ cells in iDC wells (2.30 ± 0.79% vs. 5.73 ± 1.40%). Alcohol also inhibited the increase in the number of lineage-HLA-DR+CD83+ cells in mature DC wells (1.23 ± 0.15% vs. 4.13 ± 0.62%). Conclusions:, Chronic EtOH decreases the bone marrow and circulating pools of myeloid DCs. Additionally, EtOH suppresses costimulatory molecule CD83 expression during DC transformation, which may attenuate the ability of DCs to initiate T-cell expansion. [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] Interindividual Differences in Neonatal Imitation and the Development of Action Chains in Rhesus MacaquesCHILD DEVELOPMENT, Issue 4 2009Pier Francesco Ferrari The capacity to imitate facial gestures is highly variable in rhesus macaques and this variability may be related to differences in specific neurobehavioral patterns of development. This study evaluated the differential neonatal imitative response of 41 macaques in relation to the development of sensory, motor, and cognitive skills throughout the 1st month of life. The results show that infants who imitate facial gestures display more developed skills in goal-directed movements (reaching,grasping and fine hand motor control) than nonimitators. These differences might reflect, at least in part, the differential maturation of motor chains in the parietal and motor cortices, which partly overlap with those of the mirror neuron system. Thus, neonatal imitation appears to be a predictor of future neurobehavioral development. [source] ORIGINAL ARTICLE: Epithelioid hemangioendothelioma in the right auricle of an adult, male Rhesus macaque (Macaca mulatta)JOURNAL OF MEDICAL PRIMATOLOGY, Issue 5 2010E.D. Lombardini Abstract Background, A 9-year-old, male castrate, Rhesus macaque was euthanized following a prolonged history of chronic renal failure. Results, Necropsy revealed a proliferative lesion within the right cardiac auricle composed of neoplastic epithelioid cells which infiltrated the myocardium and frequently exhibited intracytoplasmic luminae. Cells multifocally exhibited strong cytoplasmic immunoreactivity for Factor VIII-related protein (von Willebrand's factor). Conclusions, The histological characteristics of this tumor are consistent with a diagnosis of epithelioid hemangioendothelioma, an intermediate-grade vasoformative neoplasm which has to our knowledge not previously been reported in the heart of a non-human species. [source] Polymorphism in the Rhesus macaque (Macaca mulatta) NRAMP1 gene: lack of an allelic association to tuberculosis susceptibilityJOURNAL OF MEDICAL PRIMATOLOGY, Issue 1 2002Amos S. Deinard Although previous tuberculosis (TB) research has suggested that underlying genetic factors influence a host's response and ability to survive Mycobacterium infection, only recently has a gene been identified, the `natural resistance-associated macrophage protein 1' (NRAMP1) gene, which provides a degree of natural resistance to infection by some Mycobacterium species. To date, however, the role that NRAMP1 may play in resistance to Mycobacterium infection has only been examined in mouse and man. Here, we present data generated at NRAMP1 among a group of rhesus macaques (Macaca mulatta) that were euthanized because of an outbreak of Mycobacterium tuberculosis during quarantine. Data were also generated on unrelated (and healthy) rhesus macaques in order to better determine the frequency and degree of genetic polymorphism within Macaca at the NRAMP1 locus. These data represent the first study designed to examine the role that NRAMP1 may play in TB susceptibility among rhesus macaques. [source] Rhesus macaque antibody molecules: sequences and heterogeneity of alpha and gamma constant regionsIMMUNOLOGY, Issue 1 2004Franco Scinicariello Summary Rhesus macaques (Macaca mulatta) are extensively used in vaccine development. Macaques infected with simian immunodeficiency viruses (SIV) or simian-human immunodeficiency viruses (SHIV) are the best animal model currently available for acquired-immune-deficiency-syndrome-related studies. Recent results emphasize the importance of antibody responses in controlling HIV and SIV infection. Despite the increasing attention placed on humoral immunity in these models, very limited information is available on rhesus macaque antibody molecules. Therefore, we sequenced, cloned and characterized immunoglobulin gamma (IGHG) and alpha (IGHA) chain constant region genes from rhesus macaques of Indian and Chinese origin. Although it is currently thought that rhesus macaques express three IgG subclasses, we identified four IGHG genes, which were designated IGHG1, IGHG2, IGHG3 and IGHG4 on the basis of sequence similarities with the four human genes encoding the IgG1, IgG2, IgG3 and IgG4 subclasses. The four genes were expressed at least at the messenger RNA level, as demonstrated by real-time reverse transcription polymerase chain reaction (RT-PCR). The level of intraspecies heterogeneity was very high for IGHA genes, whereas IGHG genes were remarkably similar in all animals examined. However, single amino acid substitutions were present in IGHG2 and IGHG4 genes, indicating the presence of IgG polymorphism possibly resulting in the expression of different allotypes. Two IgA alleles were identified in several animals and RT-PCR showed that both alleles may be expressed. Presence of immunoglobulin gene polymorphism appears to reflect the unusually high levels of intraspecies heterogeneity already demonstrated for major histocompatibility complex genes in this non-human primate species. [source] Viral interleukin-6 encoded by rhesus macaque rhadinovirus is associated with lymphoproliferative disorder (LPD)JOURNAL OF MEDICAL PRIMATOLOGY, Issue 2009B.U. Orzechowska Abstract Background, Rhesus macaques (RM) co-infected with simian immunodeficiency virus (SIV) and rhesus macaque rhadinovirus (RRV) develop abnormal cellular proliferations characterized as extra-nodal lymphoma and retroperitoneal fibromatosis (RF). RRV encodes a viral interleukin-6 (vIL-6), much like Kaposi's sarcoma-associated herpesvirus, and involvement of the viral cytokine was examined in proliferative lesions. Methods, Formalin fixed tissue from RM co-infected with SIV and RRV were analyzed for RRV genomes by in situ hybridization and RRV vIL-6 expression by immunofluorescence analysis. Results, In situ hybridization analysis indicated that RRV is present in both types of lesions. Immunofluorescence analysis of different lymphomas and RF revealed positive staining for vIL-6. Similarly to KS, RF lesion is positive for vimentin, CD117 (c-kit), and smooth muscle actin (SMA) and contains T cell, B cell and monocytes/macrophage infiltrates. Conclusions, Our data support the idea that vIL-6 may be critical to the development and progression of lymphoproliferative disorder in RRV/SIV-infected RM. [source] Alcohol Exposure Impairs Myeloid Dendritic Cell Function in Rhesus MacaquesALCOHOLISM, Issue 9 2009Robert W. Siggins Background:, Alcohol intoxication suppresses both the innate and adaptive immunities. Dendritic cells (DCs) are the major cell type bridging the innate and acquired immune responses. At the present time, the effects of alcohol on DC development in hematopoietic tissues and the functional activities of DCs are incompletely elucidated. This study investigated the impact of chronic alcohol exposure on the alteration of hematopoietic precursor cell and DC populations in the bone marrow and peripheral blood of rhesus macaques. Methods:, Rhesus macaques were administered alcohol or isocaloric sucrose daily for a period of 3 months through surgically implanted gastric catheters. Peripheral blood mononuclear cells (PBMCs) and bone marrow cells (BMCs) were isolated for flow cytometric analysis after 3 months. Monocytes were cultured with human IL-4 (10 ng/ml) and GM-CSF (50 ng/ml) in the absence and presence of alcohol (50 mM). On day 6 of the culture, a cocktail of stimulants including IL-1, (18 ng), IL-6 (1800 U), TNF-, (18 ng), and PGE2 (1.8 ,g) were added to the designated wells for transformation of immature dendritic cells (iDCs) to mature myeloid DCs. The cells were analyzed on day 8 by flow cytometry for expression of DC costimulatory molecule expression. Results:, EtOH-treated animals had significantly lower numbers of myeloid DCs (lineage-HLA-DR+CD11c+CD123,) in both the PBMCs and BMCs compared to controls (5,654 ± 1,273/106 vs. 2,353 ± 660/106 PBMCs and 503 ± 34 vs. 195 ± 44/106 BMCs). Under culture conditions, the number of lineage-HLA-DR+CD83+ cells was low in control wells (0.38 ± 0.08%). Alcohol inhibited the increase in the number of lineage-HLA-DR+CD83+ cells in iDC wells (2.30 ± 0.79% vs. 5.73 ± 1.40%). Alcohol also inhibited the increase in the number of lineage-HLA-DR+CD83+ cells in mature DC wells (1.23 ± 0.15% vs. 4.13 ± 0.62%). Conclusions:, Chronic EtOH decreases the bone marrow and circulating pools of myeloid DCs. Additionally, EtOH suppresses costimulatory molecule CD83 expression during DC transformation, which may attenuate the ability of DCs to initiate T-cell expansion. [source] Richer milk for sons but more milk for daughters: Sex-biased investment during lactation varies with maternal life history in rhesus macaquesAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2009Katherine Hinde Lactation represents the greatest postnatal energetic expenditure for human and non-human primate females, and the ability to sustain the costs of lactation is influenced by a mother's physical condition. This is especially true for young mothers that initiate reproduction shortly after adolescence. These mothers have fewer bodily reserves available for lactation and face tradeoffs between reproduction and their own growth. Milk synthesis among captive rhesus macaques (Macaca mulatta) was investigated at the California National Primate Research Center from 2005 to 2007 (N = 114). Rhesus macaques produced low energy density milk typical of the primate order, but there was substantial individual variation among mothers in both milk energy density and yield. As a consequence, the available milk energy (AME), the product of milk energy density and milk yield, to support infant growth, development, and activity, varied tenfold among mothers. Primiparous mothers (N = 40) had fewer bodily resources, as measured by mass and body mass index, available for lactation than did multiparous mothers (N = 74) and showed poorer lactational performance. Mothers of sons produced milk of higher energy density, especially primiparous mothers, but lower milk yield, such that AME was the same for sons and daughters. Although AME from the mother was the same for sons and daughters, there was significant sexual dimorphism in infant mass. These data indicate that selection has likely favored sex-specific regulation of growth and development that is not necessarily contingent on greater maternal investment. Am. J. Hum. Biol. 2009. © 2009 Wiley-Liss, Inc. [source] Sex differences in juvenile rhesus macaque (Macaca mulatta) agonistic screams: Life history differences and effects of prenatal androgensDEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2005Michelle L. Tomaszycki Abstract This study investigated sex differences in juvenile rhesus macaque (Macaca mulatta) vocal behavior during agonistic contexts, and the effects of prenatal androgens on these differences. A total of 59 subjects (5,8 per treatment group) received exogenous androgen (testosterone enanthate), an anti-androgen (flutamide) or vehicle injections (DMSO) for 30 or 35 days during the second (early) or third (late) trimester of pregnancy. An additional 19 unmanipulated controls were included in the analysis. Screams by juvenile males and females between the ages of 1 and 3 years were compared to the screams of adult female exemplars using a discriminant function analysis. Juvenile females produced more adult-female like screams than did juvenile males. Females exposed to androgen treatment late in gestation produced a more masculine pattern of screams. Flutamide treatment in males either early or late in gestation did not significantly affect scream production. Flutamide treatments in females late in gestation, however, masculinized scream production. Androgen treatments administered late in gestation hyper-masculinized male scream production. No sex differences in the contextual usage of screams emerged. These findings suggest that both life history differences and the early hormone environment contribute to sex differences in juvenile rhesus macaque vocal production. © 2005 Wiley Periodicals, Inc. Dev Psychobiol 47: 318,327, 2005. [source] Experimental respiratory anthrax infection in the common marmoset (Callithrix jacchus)INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2008Mark S. Lever Summary Inhalational anthrax is a rare but potentially fatal infection in man. The common marmoset (Callithrix jacchus) was evaluated as a small non-human primate (NHP) model of inhalational anthrax infection, as an alternative to larger NHP species. The marmoset was found to be susceptible to inhalational exposure to Bacillus anthracis Ames strain. The pathophysiology of infection following inhalational exposure was similar to that previously reported in the rhesus and cynomolgus macaque and humans. The calculated LD50 for B. anthracis Ames strain in the marmoset was 1.47 × 103 colony-forming units, compared with a published LD50 of 5.5 × 104 spores in the rhesus macaque and 4.13 × 103 spores in the cynomolgus macaque. This suggests that the common marmoset is an appropriate alternative NHP and will be used for the evaluation of medical countermeasures against respiratory anthrax infection. [source] Resident bacteria in a mixed population of rhesus macaque (Macaca mulatta) monkeys: a prevalence studyJOURNAL OF MEDICAL PRIMATOLOGY, Issue 6 2009C.A. Carrier Abstract Background, Microflora populations residing in oropharyngeal and gastrointestinal sites defend against pathogenic bacterial colonization. Perturbations in these microbial communities may allow opportunistic pathogenic bacteria to establish themselves and cause morbidity and mortality from sepsis particularly after stressful experimental procedures. This study determined the prevalent facultative bacteria in a resident population of Macaca mulatta prior to use in experimentally induced immunosuppressive radiation studies. Methods, Standard microbiological methods were used to assess prevalent facultative bacteria in the oropharynx and rectum of 24 male M. mulatta. Results, The majority of the bacteria isolated from the oropharyngeal and rectal sites were gram-positive cocci. Species of Staphylococcus and Streptococcus predominated in all samples. Few gram-negative bacteria were isolated. Conclusions, Bacteriological assessment is recommended to identify predominant bacterial species to be prepared to provide appropriate antimicrobial therapy in non-human primates that are expected to undergo stressful immunocompromising procedures. [source] Kinetics of pronuclear development and the effects of vector type and timing of injection on the efficiency of gene transfer into rhesus macaque embryosMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 10 2008H.M. Kubisch Abstract A series of experiments was performed to determine the dynamics of pronuclear development as well as the efficiency of either adenovirus-associated (AAV) or lentivirus-derived vectors to introduce a green fluorescent protein (GFP) reporter gene into rhesus macaque (Macaca mulatta) embryos. Assessment of pronuclear development at various times after fertilization revealed that the appearance of pronuclei was determined by the presence of the first and the timing of the second polar body. The dynamics of pronuclear formation was a significant determinant of whether an oocyte reached the blastocyst stage, however, when the percentage of blastocysts were based on the number of zygotes, the timing of the appearance of polar bodies did not appear to have any effect on subsequent development. Injection of different AAV-derived vectors showed that the serotype of the vector did not affect development or the proportion of transgenic embryos. Moreover, all putative transgenic embryos proved to be expression mosaics. Injection of embryos with lentiviral vectors showed that timing of injection (before or after fertilization) had no effect on subsequent transgene expression, but that the type of reporter gene determined post-injection development and rate of transgenesis. The transfer of embryos following injection of a lentiviral vector into three recipients resulted in one pregnancy which was lost during the second trimester. Analysis of fetal tissues showed ubiquitous presence of the transgene and GFP expression in all tissues examined. These results show that lentivirus-derived vectors can efficiently transform rhesus embryos and are suitable for the generation of transgenic rhesus monkeys. Mol. Reprod. Dev. 75: 1505,1514 © 2008 Wiley-Liss, Inc. [source] Genetic characterization of specific pathogen-free rhesus macaque (Macaca mulatta) populations at the California National Primate Research Center (CNPRC)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 7 2010Sree Kanthaswamy Abstract A study based on 14 STRs was conducted to understand intergenerational genetic changes that have occurred within the California National Primate Research Center's (CNPRC) regular specific pathogen-free (SPF) and super-SPF captive rhesus macaque populations relative to their conventional founders. Intergenerational genetic drift has caused age cohorts of each study population, especially within the conventional population, to become increasingly differentiated from each other and from their founders. Although there is still only minimal stratification between the conventional population and either of the two SPF populations, separate derivation of the regular and super-SPF animals from their conventional founders has caused the two SPF populations to remain marginally different from each other. The regular SPF and, especially, the super-SPF populations have been influenced by the effects of differential ancestry, sampling, and lost rare alleles, causing a substantial degree of genetic divergence between these subpopulations. The country of origin of founders is the principal determinant of the MHC haplotype composition of the SPF stocks at the CNPRC. Selection of SPF colony breeders bearing desired genotypes of Mamu-A*01 or -B*01 has not affected the overall genetic heterogeneity of the conventional and the SPF research stocks. Because misclassifying the ancestry of research stocks can undermine experimental outcomes by excluding animals with regional-specific genotypes or phenotypes of importance, understanding founder/descendent genetic relationships is crucial for investigating candidate genes with distinct geographic origins. Together with demographic management, population genetic assessments of SPF colonies can curtail excessive phenotypic variation among the study stocks and facilitate successful production goals. Am. J. Primatol. 72:587,599, 2010. © 2010 Wiley-Liss, Inc. [source] Serotonergic influences on life-history outcomes in free-ranging male rhesus macaquesAMERICAN JOURNAL OF PRIMATOLOGY, Issue 8 2007Sue Howell Several studies have demonstrated that nonhuman primate males with low cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) exhibit antisocial behavior patterns. Included in these deleterious patterns are impulse control deficits associated with violence and premature death. No studies to date have longitudinally studied the long-term outcome of young subjects with low CSF 5-HIAA concentrations as they mature into adults. In this study we examined longitudinal relations among serotonergic and dopaminergic functioning, as reflected in CSF metabolite concentrations, aggression, age at emigration, dominance rank, and mortality in free-ranging rhesus macaque (Macaca mulatta) males. Our results indicate long-term consistency of individual differences in levels of 5-HIAA in CSF in the subject population from the juvenile period of development through adulthood. We found a significant negative correlation between 5-HIAA concentrations measured in juveniles and rates of high-intensity aggression in the same animals as adults. Further, CSF 5-HIAA concentrations were lower in juveniles that died than in animals that survived. For the young animals that migrated there was a positive correlation between CSF 5-HIAA concentration and age at emigration, whereas for the animals that remained in their troop until later in sexual maturity there was a negative correlation between CSF 5-HIAA concentration and age of emigration. After animals emigrated to a new troop, social dominance rank in the new troop was positively correlated with early family social dominance rank, but inversely correlated with juvenile CSF 5-HIAA concentrations. Taken together, our findings suggest that males with low central serotonin levels early in life delay migration and show high levels of violence and premature death, but the males that survive achieve high rank. These findings indicate that longitudinal measures of serotonergic and dopaminergic functioning are predictive of major life-history outcomes in nonhuman primate males. Low concentrations of CSF 5-HIAA are associated with negative life-history patterns characterized by social instability and excessive aggression, and positive life-history patterns characterized by higher dominance rank. Am. J. Primatol. 69:851,865, 2007. © 2007 Wiley-Liss, Inc. [source] In vivo gene marking of rhesus macaque long-term repopulating hematopoietic cells using a VSV-G pseudotyped versus amphotropic oncoretroviral vectorTHE JOURNAL OF GENE MEDICINE, Issue 4 2004Patricia A. Shi Abstract Background Gene transfer efficiency into primitive hematopoietic cells may be limited by their expression of surface receptors allowing vector entry. Vectors pseudotyped with the vesicular stomatitis virus (VSV-G) envelope do not need receptors to enter cells, and therefore may provide superior transduction efficiency. Methods Using a competitive repopulation model in the rhesus macaque, we examined in vivo gene marking levels of blood cells transduced with two vectors: (i) a VSV-G pseudotyped retrovirus and (ii) a conventional amphotropic retrovirus. The VSV-G vector, containing the human glucose-6-phosphate dehydrogenase (G6PD) gene, was constructed for treatment of severe hemolytic anemia caused by G6PD deficiency. Three myeloablated animals were transplanted with peripheral blood CD34+ cells, half of which were transduced with the VSV-G vector and the other half with the amphotropic vector. Results In all animals post-transplantation, levels of in vivo marking in circulating granulocytes and mononuclear cells were similar: 1% or less with both vectors. In one animal, the human G6PD enzyme transferred by the VSV-G vector was expressed in erythrocytes, early after transplantation, at a level of 45% of the endogenous rhesus G6PD protein. Conclusions In a clinically relevant animal model, we found similar in vivo marking with a VSV-G pseudotyped and a standard amphotropic oncoretroviral vector. Amphotropic receptor expression may not be a limiting factor in transduction efficiency, but VSV-G pseudotypes possess other practical advantages that may make them advantageous for clinical use. Copyright © 2004 John Wiley & Sons, Ltd. [source] Expression, purification, crystallization and preliminary X-ray diffraction analysis of rhesus macaque CD8,, homodimerACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 4 2010Lili Zong As a T-cell co-receptor, CD8 binds to MHC class I molecules and plays a pivotal role in the activation of cytotoxic T lymphocytes. To date, structures of CD8 have been solved for two different mammals: human and mouse. The infection of rhesus macaques (Macaca mulatta) by simian immunodeficiency virus (SIV) is the best animal model for studying HIV. In this study, the rhesus macaque CD8 (rCD8) ,, homodimer was obtained and rCD8, exodomain protein crystals were successfully obtained for further structural analysis. Diffraction data were collected to a resolution of 2.4,Å. The crystal belonged to space group P212121, with unit-cell parameters a = 46.52, b = 56.28, c = 82.40,Å. These data will facilitate further studies on the structural differences between these CD8 structures and the cellular immune responses of rhesus macaque. [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] Changes In Rhesus Macaque ,Coo' Vocalizations during Early DevelopmentETHOLOGY, Issue 10 2000Kurt Hammerschmidt In order to test whether ,coo' calls of young rhesus macaques, Macaca mulatta, undergo some modifications during early development, and to explore which factors may influence these changes, we studied the ontogeny of their contact call, the ,coo' call. Vocalizations were recorded during brief periods of social separation. Infants were either raised with their mothers and other conspecifics, or separated from their mothers at birth and housed in a nursery with other infants. We recorded calls uttered in the separation context from 20 infants. We digitized the first 50 calls of a given series and subjected them to a Fourier transform. From each frequency,time spectrum, we extracted 65 acoustic parameters using a software program (LMA 5.9). We then used a cluster analysis to separate the ,coo' calls from other call types. With increasing age, the ,coos' dropped in pitch and became more even. The course of amplitude became more constant and the call duration increased slightly. Nevertheless, we found a high intra-individual variation throughout the 5 mo. Neither rearing condition nor sex had any apparent influence on age-related changes in ,coo' structure. With one exception, all parameters that correlated with age could be explained by variation in weight. Therefore, we conclude that growth is the main factor accounting for the observed changes. [source] Intestinal double-positive CD4+CD8+ T,cells are highly activated memory cells with an increased capacity to produce cytokinesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2006Bapi Pahar Dr. Abstract Peripheral blood and intestinal CD4+CD8+ double-positive (DP) T,cells have been described in several species including humans, but their function and immunophenotypic characteristics are still not clearly understood. Here we demonstrate that DP T,cells are abundant in the intestinal lamina propria of normal rhesus macaques (Macaca mulatta). Moreover, DP T,cells have a memory phenotype and are capable of producing different and/or higher levels of cytokines and chemokines in response to mitogen stimulation compared to CD4+ single-positive T,cells. Intestinal DP T,cells are also highly activated and have higher expression of CCR5, which makes them preferred targets for simian immunodeficiency virus/HIV infection. Increased levels of CD69, CD25 and HLA-DR, and lower CD62L expression were found on intestinal DP T,cells populations compared to CD4+ single-positive T,cells. Collectively, these findings demonstrate that intestinal and peripheral blood DP T,cells are effector cells and may be important in regulating immune responses, which distinguishes them from the immature DP cells found in the thymus. Finally, these intestinal DP T,cells may be important target cells for HIV infection and replication due to their activation, memory phenotype and high expression of CCR5. [source] How the parallel channels of the retina contribute to depth processingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2007Peter H. Schiller Abstract Reconstructing the third dimension in the visual scene from the two dimensional images that impinge on the retinal surface is one of the major tasks of the visual system. We have devised a visual display that makes it possible to study stereoscopic depth cues and motion parallax cues separately or in concert using rhesus macaques. By varying the spatial frequency of the display and its luminance and chrominance, it is possible to selectively activate channels that originate in the primate retina. Our results show that (i) the parasol system plays a central role in processing motion parallax cues; (ii) the midget system plays a central role in stereoscopic depth perception at high spatial frequencies, and (iii) red/green colour selective neurons can effectively process both cues but blue/yellow neurons cannot do so. [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] THIS ARTICLE HAS BEEN RETRACTED STEALTH matters: a novel paradigm of durable primate allograft toleranceIMMUNOLOGICAL REVIEWS, Issue 1 2001J. M. Thomas Summary: We review a novel strategy for tolerance induction developed in rhesus macaques and termed STEALTH. We summarize the evolution of the STEALTH model, the results of successful trials in inducing long-term, stable transplant tolerance in rhesus kidney and diabetic islet recipients and discuss information related to the mechanism by which durable tolerance is induced. STEALTH tolerance is induced by a 3-day treatment course of CD3, immunotoxin (IT) combined with a 14-day treatment with deoxyspergualin (DSG). IT causes profound depletion of sessile lymph node T cells as well as the more accessible circulating T cells. DSG, an inhibitor of HSC 70-mediated NF-,B nuclear translocation, arrests maturation of myeloid dendritic cells, blocks production of proinflammatory cytokines induced by IT administration, and promotes systemic production of Th2 type cytokines that persist indefinitely. Such Th2 cytokine deviation has not been reported in NHP transplant recipients. These studies provide proof of principle in a preclinical model that prevention of both acute and chronic allograft rejection, for at least 2.2,4.9 years of follow-up, can be achieved in NHP in the absence of chronic immunosuppressive drugs or other interventions. This strategy for inducing NHP tolerance is discussed in relation to current tolerance paradigms. [source] Expression of CD8, identifies a distinct subset of effector memory CD4+ T lymphocytesIMMUNOLOGY, Issue 2 2006Iole Macchia Summary Circulating CD4+ CD8+ T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4+ CD8+ T cells in rhesus macaques. Two distinct populations of CD4+ CD8+ T cells were identified: the dominant one was CD4hi CD8lo and expressed the CD8,, homodimer, while the minor population was CD4lo CD8hi and expressed the CD8,, heterodimer. The majority of CD4hi CD8,lo T cells exhibited an activated effector/memory phenotype (CCR5lo CD7, CD28, HLA-DR+) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus-specific T cells was enriched five-fold in CD4hi CD8,lo T cells compared to single-positive CD4+ T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)-specific T cells. Cross-sectional studies of SIV-infected animals demonstrated that the frequency of CD4hi CD8,lo T cells was lower in wild-type SIV-infected animals compared to uninfected controls, although prospective studies of SIV-infected animals demonstrated depletion of CD4hi CD8,lo lymphocytes only in a subset of animals. Taken together, these data suggest that CD4+ T cells expressing CD8, represent an effector/memory subset of CD4+ T cells and that this cell population can be depleted during the course of SIV infection. [source] Rhesus macaque antibody molecules: sequences and heterogeneity of alpha and gamma constant regionsIMMUNOLOGY, Issue 1 2004Franco Scinicariello Summary Rhesus macaques (Macaca mulatta) are extensively used in vaccine development. Macaques infected with simian immunodeficiency viruses (SIV) or simian-human immunodeficiency viruses (SHIV) are the best animal model currently available for acquired-immune-deficiency-syndrome-related studies. Recent results emphasize the importance of antibody responses in controlling HIV and SIV infection. Despite the increasing attention placed on humoral immunity in these models, very limited information is available on rhesus macaque antibody molecules. Therefore, we sequenced, cloned and characterized immunoglobulin gamma (IGHG) and alpha (IGHA) chain constant region genes from rhesus macaques of Indian and Chinese origin. Although it is currently thought that rhesus macaques express three IgG subclasses, we identified four IGHG genes, which were designated IGHG1, IGHG2, IGHG3 and IGHG4 on the basis of sequence similarities with the four human genes encoding the IgG1, IgG2, IgG3 and IgG4 subclasses. The four genes were expressed at least at the messenger RNA level, as demonstrated by real-time reverse transcription polymerase chain reaction (RT-PCR). The level of intraspecies heterogeneity was very high for IGHA genes, whereas IGHG genes were remarkably similar in all animals examined. However, single amino acid substitutions were present in IGHG2 and IGHG4 genes, indicating the presence of IgG polymorphism possibly resulting in the expression of different allotypes. Two IgA alleles were identified in several animals and RT-PCR showed that both alleles may be expressed. Presence of immunoglobulin gene polymorphism appears to reflect the unusually high levels of intraspecies heterogeneity already demonstrated for major histocompatibility complex genes in this non-human primate species. [source] Evaluation of the use of coconut to treat chronic diarrhea in rhesus macaques (Macaca mulatta)JOURNAL OF MEDICAL PRIMATOLOGY, Issue 6 2008J.L. Wilk Abstract Background, Chronic diarrhea can be challenging to manage in captive rhesus macaques (Macaca mulatta) leading to ongoing diagnostics, medications, monitoring, and potential euthanasia. Coconut has been used as a dietary supplement for people with inflammatory bowel disease, with anecdotal reports of decreased diarrhea following the dietary addition. A dietary trial in rhesus macaques was initiated to evaluate the hypothesis that dietary coconut decreases symptoms of chronic diarrhea in rhesus macaques. Methods, Ten rhesus macaques with chronic diarrhea were selected for the trial. Five of the subjects were fed coconut macaroons and five of the subjects were fed a sham cookie. Stool consistency was monitored daily for both groups. Results and conclusions, Data of chi-squared analysis obtained from eight rhesus macaques with chronic diarrhea showed that the use of coconut macaroons as a dietary supplement did not have a statistically significant effect on their diarrhea. [source] The efficacy of orally dosed ketamine and ketamine/medetomidine compared with intramuscular ketamine in rhesus macaques (Macaca mulatta) and the effects of dosing route on haematological stress markersJOURNAL OF MEDICAL PRIMATOLOGY, Issue 3 2008Andrew N Winterborn Abstract Background, This study compared the efficacy of two orally-dosed (PO) anaesthetic regimens for chemical immobilization in rhesus macaques (Macaca mulatta), versus the standard protocol of intramuscular (TM) ketamine. In addition, the effects of dosing route on haematological stress markers were evaluated. Methods, Testing was conducted on 18 chronically housed animals. Animals were trained to accept oral dosing and then randomly assigned to one of three drug regimens: (1) ketamine IM, (2) ketamine PO, (3) Ketamine/medetomidine PO. Sedation levels for each regimen were evaluated. Results, Oral dosing alone was not sufficient to achieve a plane of sedation that allowed for safe handling. Serum cortisol and glucose levels were unchanged across groups, although differences were observed in the leukogram profiles. Conclusion, The oral dosages used in this study fell short in providing adequate sedation for safe handling for routine veterinary procedures. Leukogram profiles indicated that orally dosed animals experienced a higher level of stress. [source] Genetic characterization of wild and captive rhesus macaques in China*JOURNAL OF MEDICAL PRIMATOLOGY, Issue 2 2008J. Satkoski Abstract The genetic structures of wild and captive rhesus macaque populations within China were compared by analyzing the mtDNA sequences of 203 captive-bred Chinese rhesus macaques with 77 GenBank sequences from wild-caught animals trapped throughout China. The genotypes of 22 microsatellites of captive Chinese rhesus macaques were also compared with those of captive Indian animals. The Chinese population is significantly differentiated from the Indian population and is more heterogeneous. Thus, compared with Indian rhesus macaques the phenotypic variance of traits with high heritability will be inflated in Chinese animals. Our data suggest that the western Chinese provinces have more subdivided populations than the eastern and southern Chinese provinces. The southern Chinese populations are the least structured and might have been more recently established. Human-mediated interbreeding among captive Chinese populations has occurred, implying that Chinese breeding strategies can influence the interpretation of biomedical research in the USA. [source] Assessment of progestin-only therapy for endometriosis in macaqueJOURNAL OF MEDICAL PRIMATOLOGY, Issue 2008G. Maginnis Abstract Background, Endometriosis is a condition where endometrium-like tissue forms lesions at ectopic sites outside the uterus. In women, oral contraceptive pills and progestins are often prescribed as therapy for early stage endometriosis. In contrast, in macaques the disease is frequently advanced at the time of diagnosis and ovariectomy is the standard therapy. However, surgery is contraindicated in many patients. A review of 15 endometriosis cases over the past 10 years at the Oregon National Primate Research Center (ONPRC) revealed that 5 failed to show improvement after ovariectomy and were subsequently euthanized. Therefore, our goal was to assess the feasibility of treating endometriosis in macaques with chronic progesterone (P) as an alternative therapy for the disease. Methods, Seven adult rhesus macaques with advanced endometriosis were identified by clinical symptoms and endometriosis was confirmed by abdominal palpation, ultrasound examination, and/or aspiration of menstrual blood from abdominal cysts. The patients were chronically treated with Silastic capsules that released 5,7 ng P /ml in blood for up to 20 months. During treatment the patients were assessed daily and scored numerically for appetite, activity, attitude, abdominal discomfort and menstruation by the Clinical Veterinary staff. The patients were then re-examined by abdominal palpation and ultrasound for the disease at the end of treatment. Results, During the first 2 weeks of treatment, endometriotic symptoms improved significantly in all the patients (P < 0.05). This was associated with a significant increase in body weight and significant reduction in abdominal discomfort and menstrual bleeding. Two of the patients gradually developed increased symptoms of the disease after 5 months of treatment. Post-treatment abdominal examination revealed that 2/5 patients continued to have an abdominal mass even though symptoms were suppressed. Conclusions, We conclude that continuous P treatment of rhesus monkeys provides therapeutic benefit to reduce symptoms of endometriosis and may provide an option for cases where ovariectomy is contraindicated. Supported by RR-00163. [source] | ||||||||||||||||